Patent Application
20230301711
The present disclosure is directed generally to devices and methods for ablating malignant lung tumors and more particularly to ablating lung tumors with an approach through the patient's airway.
Lung cancer remains the leading cause of cancer-related deaths in the world. In fact, lung cancer is responsible for more deaths each year in this country than breast cancer, colon cancer, and prostate cancer combined. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer; it is named for the type of cell within the lung where the cancer originates. Approximately 75 to 80% of individuals with lung cancer have NSCLC. Early NSCLC refers to cancer that has not spread widely outside of its site of origin. The earlier lung cancer is detected and treated, the better the outcome. The current standard treatment for early lung cancer consists of the surgical removal of as much of the cancer as possible followed by chemotherapy and/or radiation therapy.
Surgical removal of a lung or lobe is the gold standard treatment for treating stage 1 or 2 non-small-cell-lung-cancer (NSCLC). Unfortunately, only about 15% to 30% of patients diagnosed with lung carcinoma each year are surgical candidates. Particularly, many patients with concurrent Chronic Obstructive Pulmonary Disease (COPD) are not considered suitable for surgery.
Percutaneous pulmonary radiofrequency ablation (RFA) with a needle electrode inserted through the chest wall under CT guidance has become an increasingly adopted treatment option for primary and metastatic lung tumours. The immediate technical success rate is over 95%, with a low periprocedural mortality rate and 8 to 12% major complication rate. Pneumothorax represents the most frequent complication but requires a chest tube drain in less than 10% of cases. Sustained complete tumour response has been reported in 85% to 90% of target lesions.
Bronchoscopic ablation of lung tumors is perceived by many as the next frontier in non-surgical thermal tumor ablation but has been held back by lack of specialized equipment for creation of large enough volume of destroyed tissue at the targeted site. This limitation is additionally challenged by the necessity to operate through the working channel of the bronchoscope, by the difficulty of endoscopically navigating the ablation electrodes to targeted tumors and by the specific properties of lung tissue that is amply perfused by blood flow, cooled by perfusion, evaporation and convection, and incorporates a large volume of air that increases the RF path electrical impedance and can also deform the volume of targeted tissue in phase with breathing. The latter consideration led to research preference being given to microwave energy, since microwave energy travels through air well. However, there is an advantage of simplicity and efficiency in RF heating of tissues that are appreciated in the field.
In light of the foregoing there remains a need for improvements to RF energy delivery methods and devices that prove suitability for bronchoscope-delivered ablation of lung tumors. It is further desired for the devices to be flexible and relatively soft and fit in working channels that are small in diameter, preferable less than 2 mm, in order to reach tumors that are closer to the periphery of the lung.
This disclosure is related to methods, devices, and systems for transbronchial ablation of a lung tumor. Aspects of the disclosure include:
Devices and systems suitable for delivering conductive fluid (e.g. HTS) into the airway through the endobronchial ablation catheter to reduce tissue impedance and increase the effective RF energy delivery electrode size.
Endobronchial navigation using CT image data to create a navigation plan to facilitate advancing an ablation catheter through a bronchoscope and a branch of a bronchus of a patient towards the nodule. Electromagnetic tracking may also be utilized in conjunction with the CT data to facilitate guiding the ablation catheter through the branch of the bronchus to the nodule. The ablation catheter may be positioned within one of the airways of the branched luminal networks adjacent to or within the nodule or point of interest. Once in position, fluoroscopy may be used to visualize the ablation catheter as it is further maneuvered towards the nodule or point of interest. Other imaging techniques, such as MRI, ultrasound, etc., may be used in conjunction with, or in lieu of, fluoroscopy or CT in combination with navigational bronchoscopy. Optionally, the endobronchial ablation catheter may be fitted with sensors (e.g. 3D electromagnetic coils, Fiber Bragg Grating shape sensors, etc.) compatible with the navigational bronchoscopy system available on site.
One or more aspects of the invention are disclosed here below.
A first aspect relates to a system for treatment of a target region of lung tissue, the system comprising: at least one a flow regulator configured to be interposed between a conductive fluid source and a conductive fluid outlet positionable at or in proximity of the target region of lung tissue, the flow regulator being further configured for controlling a flow rate or a bolus quantity of conductive fluid coming from the fluid source and delivered to the conductive fluid outlet; a controller communicatively connectable with said flow regulator and with at least one sensor, with the at least one sensor being configured for detecting values taken by at least one control parameter representative of a physical property, wherein the physical property is one of temperature (T), pressure (p), electric impedance (Z), or electric conductivity (C) of material present at or in proximity of the target region of lung tissue; wherein the controller is configured for:
A 2nd aspect according to the first aspect wherein in the low delivery mode: the flow rate of conductive fluid delivered to the conductive fluid outlet is equal or below a set low flow rate smaller than 50% of the set high flow rate, or the bolus quantity of conductive fluid delivered to the conductive fluid outlet is equal or below a set low bolus quantity smaller than 50% of the set high bolus quantity.
A 3rd aspect according to the first aspect or 2nd aspect, wherein in the low delivery mode the set low flow rate is between 0 and 5 ml/min or wherein the set low bolus quantity is between 0 and 10 ml.
A 4th aspect according to the first or 2nd or 3rd wherein in the high delivery mode the set high flow rate is between 2 and 16 ml/min or the set high bolus quantity is between 0.3 and 60 ml.
A 5th aspect according to any one of the first to 4th aspects, wherein controlling the flow regulator comprises repeatedly executing said control cycle.
A 6th aspect according to any one of the first to 5th aspects, comprising at least one ablation element positionable at the target region of the lung tissue and connectable to an ablation source.
A 7th aspect according to the 6th aspect, comprising at least one flexible shaft configured to advance through an airway passage of a lung and having an active portion positionable at the target region of the lung tissue and including the at least one ablation element.
An 8th aspect according to any one of the preceding first to 7th aspects, comprising the at least one sensor, the sensor being configured to be positionable at the target region of the lung tissue.
A 9th aspect according to the 7th aspect in combination with any one of aspects 1-6 and 8, wherein the at least one sensor is carried by the active portion of said flexible shaft.
A 10th aspect according to the 7th aspect in combination with any one of aspects 1-6 and 8, wherein the at least one sensor is configured to be positioned in correspondence of a volume surrounding the active portion of said flexible shaft.
An 11th aspect according to aspect 9 or 10, wherein the at least one sensor is configured for sensing values taken by the at least one control parameter, and wherein the physical property is one of temperature, pressure, electric impedance, or electric conductivity of material present in a volume surrounding the active portion.
A 12th aspect according to any one of the preceding aspects comprising the conductive fluid outlet which is configured to be placed in fluid communication with the conductive fluid source.
A 13th aspect according to aspect 7 and 12, wherein the conductive fluid outlet is carried by the flexible shaft active portion.
A 14th aspect according to aspect 7 and 12, wherein the conductive fluid outlet is configured to be positioned in correspondence of said volume surrounding the active portion.
A 15th aspect according to any one of the preceding aspects 6-14, wherein the controller is connectable with said ablation source and configured for controlling the ablation energy source to deliver ablation energy to the at least one ablation element.
A 16th aspect according to the 15th aspect, further wherein the controller is configured for executing said steps of: receiving from said sensor signals representative of sensed values of the control parameter, and controlling the flow regulator based on one or more sensed values of the control parameter and executing, optionally repeatedly executing, said control cycle, while the controller commands the ablation energy source to deliver ablation energy to the at least one ablation element.
A 17th aspect according to any one of the preceding aspects 7-16, comprising an electrical connector carried by the flexible shaft and adapted to electrically connect the at least one ablation element to the ablation source.
An 18th aspect according to any one of the preceding aspects, wherein the control cycle includes: verifying if one or more sensed values of the control parameter fall below a set low threshold (T_Low), and wherein said controlling the flow regulator to low delivery mode is executed if the one or more sensed values of the control parameter fall below the set low threshold (T_Low).
A 19th aspect according to any one of the preceding aspects, wherein the control cycle includes: verifying if one or more sensed values of the control parameter exceed a set high threshold (T_High, Z_High), and wherein said controlling the flow regulator to high delivery mode is executed if the one or more sensed values of the control parameter exceed the set high threshold (T_High, Z_High).
A 20th aspect according to any one of the preceding aspects, wherein the control cycle includes: periodically verifying if one or more sensed values of the control parameter fall below a set low threshold (T_Low), switching the flow regulator from high delivery mode to low delivery mode when the one or more sensed values of the control parameter fall below the set low threshold (T_Low); optionally, wherein said step of periodically verifying is executed at least 10 times per second.
A 21st aspect according to any one of the preceding aspects, wherein the control cycle includes: periodically verifying if one or more sensed values of the control parameter exceed a set high threshold (T_High, Z_High), switching the flow regulator from low delivery mode to high delivery mode when the one or more sensed values of the control parameter exceed the set high threshold (T_High, Z_High); optionally, wherein said step of periodically verifying is executed at least 10 times per second.
A 22nd aspect according to any one of the preceding aspects wherein the controller is configured for repeating the control cycle a plurality of times during a same treatment session.
A 23rd aspect according to aspect 22, wherein the controller is configured to control the flow regulator in high delivery mode or in low delivery mode for a respective time interval, and wherein a duration of said respective time intervals is either predetermined or determined by detection of a triggering event.
A 24th aspect according to aspect 23, wherein the controller is configured to determine duration of said time intervals by detection of a triggering event, wherein detection of the triggering event comprises one or more of:
A 25th aspect according to aspect 22 or 23 or 24, wherein the controller is configured to execute the same treatment session which includes a plurality of time intervals where the flow regulator is adjusted to low delivery mode intercalated by time intervals where the flow regulator is adjusted to high delivery mode, thereby reducing the overall amount of conductive fluid delivered over said treatment session while maintaining under control the detected values of the parameter.
A 26th aspect according to any one of the preceding aspects, wherein the step of controlling the flow regulator to low delivery mode comprises: adjusting the flow regulator to maintain the flow rate of conductive fluid to the conductive fluid outlet equal or below said set low flow rate during a low delivery time interval (Flow Low Time), in particular comprised between 1 to 10 seconds; or adjusting the flow regulator to deliver to the conductive fluid outlet the bolus quantity of conductive fluid equal or below said set low bolus quantity within a low delivery time interval (Flow Low Time), in particular comprised between 1 to 10 seconds.
A 27th aspect according to aspect 26, wherein the cycle comprises a sub-routine optionally executed after expiration of said low delivery time interval, said sub-routine including:
A 28th aspect according to any one of the preceding aspects, wherein the step of controlling the flow regulator to high delivery mode comprises:
A 29th aspect according to aspect 28, wherein the cycle comprises a sub-routine optionally executed after expiration of said high delivery time interval, said sub-routine including:
A 30th aspect according to aspect 29, wherein the cycle provides for repeating the sub-routine of aspect 29 until when the further step of verifying if one or more values of the sensed falls below the set low-threshold (T_Low) is positively passed.
A 31st aspect according to aspect 16 and 30, wherein the controller is configured to interrupt or reduce delivery of ablation energy to the at least one ablation element if it has determined that, after a predetermined number of repetitions of the subroutine of aspect 29, the step of verifying if one or more values of the sensed fall below the set low threshold (T_Low) is not positively passed.
A 32nd aspect according to any one of the preceding aspects wherein the cycle comprises:
A 33rd aspect according to any one of the preceding aspects 6 to 32, wherein the controller is configured for maintaining power supplied by the ablation energy source in a range comprised between 20 and 200 W over a major portion of the treatment session, optionally over the entire treatment session.
A 34th aspect according to any one of preceding aspects 6-33, wherein the controller is configured to increase power supplied by the ablation energy source from an initial value to a regimen value, during an initial portion of the treatment session optionally lasting between 10% and 30% of the entire treatment session.
A 35th aspect according aspect 34, wherein the controller is configured to maintain power supplied by the ablation energy source at the regimen value during a major portion of the treatment session following said initial portion of the treatment session.
A 36th aspect according to aspect 35, wherein the initial value is comprised between 20 W and 80 W and wherein the regimen value is comprised between 40 W and 200 W, further wherein the initial value smaller than 80% of the regimen value, optionally smaller than 50% of the regimen value.
A 37th aspect according to any one of the preceding aspects 22-36 wherein the treatment session has a total treatment duration comprised between 30 seconds and 30 min.
A 38th aspect according to any one of preceding aspects 6-37, wherein the controller is configured to automatically stop delivery of power from the ablation energy source and automatically command the flow regulator to stop delivery of conductive fluid when the treatment duration has expired.
A 39th aspect according to any one of the preceding aspects 22-38, wherein the controller is configured to control the flow regulator to impose that: a maximum volume of conductive fluid delivered during the treatment session is comprised between 0.3 ml and 60 ml, and/or an average flow rate of conductive fluid maintained during the treatment session is of 0.1 to 15 ml/min, in particular wherein the controller is configured to automatically stop delivery of power from the ablation energy source and/or automatically command the flow regulator to stop delivery of conductive fluid when said maximum of conductive fluid delivered has been reached.
A 40th aspect according to any one of the preceding aspects 1-39 in combination with one of aspects 18-21, wherein the set high threshold (T_High) is greater than the set low threshold (T_Low).
A 41st aspect according to aspect 40 in combination with aspect 24, wherein the set very high threshold (T_Overheat) is greater than the set high threshold (T_High).
A 42st aspect according to any one of the preceding aspects, wherein the physical property is the temperature of material present at the target region, in particular when this aspect also depends upon aspect 11 the physical property is the temperature of material present in the volume surrounding the active portion.
A 43rd aspect according to aspects 40 and 42, wherein said set low threshold (T_Low) is 60 to 95° C.
A 44th aspect according to aspect 40 in combination with one of aspects 42 or 43, wherein said set high threshold (T_High) is from above 75° C. to 105° C.
A 45th aspect according to aspect 41 in combination with one of aspects 42 or 43 or 44, wherein said set very high threshold (T_Overheat) is between 85 to 115° C.
A 46th aspect according to any one of the preceding aspects 1-45, wherein the ablation energy source is a radiofrequency generator and wherein the controller is configured to control the radiofrequency generator to deliver RF, having a power in a range of 1 to 200 W, in particular comprised between 20 and 200 W, for a duration of 30 seconds to 30 minutes.
A 47th aspect according to any one of the preceding aspects 1 to 46, wherein the flow regulator comprises: a pump, optionally a syringe pump or a peristaltic pump or an infusion pump, or a valve.
A 48th aspect according to any one of the preceding aspects 7-47, comprising: a conductive fluid source configured to deliver a hypertonic saline solution; a fluid port connectable to the conductive fluid source and in fluid communication with the conductive fluid outlet, optionally, wherein the hypertonic saline solution includes a reverse phase transition polymer and water, which may transition to higher viscosity when transitioned from below body temperature to body temperature.
A 49th aspect according to aspect 48, wherein the hypertonic saline solution comprises one or more physiologically acceptable solutes and has a theoretical Osmolarity between 0.8 and 15 Osm/L, calculated according to the formula
A 50th aspect according to aspect 48 or 49, wherein the hypertonic saline solution comprises sodium chloride (NaCl) at a concentration of between 3% to 30% (w/v).
A 51st aspect according to any one of the preceding aspects 7-50, wherein the flexible shaft is the flexible shaft of an ablation catheter.
A 52nd aspect according to aspect 51, wherein the ablation catheter has a/the fluid port that is at a proximal end of the flexible shaft and is in fluid communication with the conductive fluid outlet which is located at the active portion of the flexible shaft.
A 53rd aspect according to any one of the preceding aspects 7-52, wherein the active portion is a distal end portion of the flexible shaft.
A 54th aspect according to any one of the preceding aspects 7-53 comprising at least one space occluder operative at or proximate to the flexible shaft active portion, in particular at or proximate to the flexible shaft distal end portion.
A 55th aspect according to aspect 54, wherein the space occluder is one of a tapered shaft section, a deployable balloon, a deployable valve, a deployable stent.
A 56th aspect according to aspect 54 or 55, wherein the occluder comprises a deployable occlusion balloon having a first cross section width of 1 to 30 mm, a length in a range of 5 to 30 mm, and wherein the occlusion balloon is configured to expand to occlude a portion of the airway.
A 57th aspect according to aspect 56, wherein the first cross section width is at a proximal region of the deployable occlusion balloon, a second cross section width in a range of 1 to 30 mm is at a distal region of the balloon, and a cross section width between the first and second cross section width is less than both the first and second cross section width.
A 58th aspect according to aspect 56, wherein the first cross section width is at a proximal region of the deployable occlusion balloon, and a second cross section width in a range of 1 to 20 mm and less than the first cross section width is at a distal region of the balloon.
A 59th aspect according to any one of the preceding aspects 7-58, comprising a tubular sheath or bronchoscope receiving said flexible shaft, wherein at least the active portion, in particular the distal end portion, of the flexible shaft is configured to emerge from the tubular sheath or bronchoscope.
A 60th aspect according to aspect 59, in combination with any one of aspects 54 to 58, wherein the space occluder is carried by the tubular sheath or bronchoscope.
A 61st aspect according to any one of aspects 54 to 58, wherein the at least one space occluder is directly carried by the flexible shaft or by another shaft.
A 62nd aspect according to any one of aspects 54 to 61, further comprising an inflating lumen extending through the flexible shaft and having a proximal end connectable to a source of a fluid, optionally a source of liquid or a source of gas, and a distal end in fluid communication with inside of the balloon.
A 63rd aspect according to any one of the preceding aspects 7 to 62, wherein the flexible shaft comprises depth markers at least on 5 cm of the proximal region and 5 cm of the distal region.
A 64th aspect according to any one of the preceding aspects 7 to 62, comprising at least one suction opening at the flexible shaft distal end portion configured to be placed in fluid communication with a vacuum source to aspirate air from a lung volume surrounding the distal end portion of the shaft.
A 65th aspect according to aspect 64, in combination with any one of aspects 54 to 63, wherein the at least one suction opening is positioned distal with respect to the space occluder.
A 66th aspect according to aspect 64, in combination with any one of aspects 54 to 63, comprising an additional space occluder operative at or proximate to the shaft distal end portion, in particular wherein the additional space occluder is one of a deployable balloon, a deployable valve, a deployable stent, and wherein the at least one suction opening is positioned between the space occluder and the additional space occluder.
A 67th aspect according to aspect 65 or 66, wherein the at least one conductive fluid outlet is positioned distal with respect to the space occluder or between the space occluder and the additional space occluder.
A 68th aspect according to any one of aspects 54 to 67, wherein the at least one sensor is positioned distal to the space occluder or between the space occluder and the additional space occluder.
A 69th aspect according to aspect 67, wherein the at least one sensor is carried by the flexible shaft distal end portion and wherein the physical property is of one of temperature, pressure, electric impedance, or electric conductivity of material surrounding the distal end portion of the flexible shaft.
A 70th aspect according to aspect 68 or 69, wherein the at least one sensor comprises a first sensor positioned proximal to the ablation element and a second sensor positioned distal to the ablation element.
A 71st aspect according to any one of the preceding aspects 7 to 70, wherein the at least one ablation element comprises an ablation element having a rounded distal tip positioned at a distal tip of the flexible shaft.
A 72nd aspect according to aspect 64, in combination with any of aspects 54 to 63 and 65 to 71, comprising: a common lumen extending through the flexible shaft and having a proximal end, selectively connectable to at least one of the source of the conductive liquid and the vacuum source, and a distal end, forming a common opening defining said at least one outlet and said at least one suction opening; or a dedicated irrigation lumen and a dedicated air suction lumen, with the irrigation lumen connected to the at least one outlet and extending through the catheter flexible shaft, the irrigation lumen having an inlet port configured to be connected to the source of conductive fluid, and with the air suction lumen connected to the at least one air suction opening and extending through the catheter flexible shaft, the air suction lumen having a suction port configured to be connected to the source of vacuum.
A 73rd aspect according to any one of the preceding aspects 7-72, wherein the flexible shaft has an outer diameter less than or equal to 2 mm.
A 74th aspect according to any one of the preceding aspects 7-73, wherein at least a portion of the flexible shaft is capable of turning such that a bend in the shaft has a radius of curvature of at least as 7 mm.
A 75th aspect according to any one of the preceding aspects 7-74, wherein the flexible shaft has a length of at least 50 cm.
A 76th aspect according to any one of the preceding aspects 7-75, wherein the elongated shaft has a guidewire lumen in the distal end portion configured to receive a guidewire.
A 77th aspect according to aspects 72 and 76, wherein the suction lumen and guidewire lumen are formed by a common lumen.
A 78th aspect according to any one of the preceding aspects 6-77, wherein the ablation element comprises at least one electrode characterized by one or more of the following features: total surface area not greater than 120 mm2; diameter in a range of 0.5 to 2 mm; length in a range of 3 to 20 mm.
A 79th aspect according to any one of the preceding aspects 6-78, wherein the at least one ablation element includes at least two electrodes, and wherein a separation between electrodes is between five to fifteen mm.
An 80th aspect according to any one of the preceding aspects including an interface component connectable with said at least one sensor and at least communicatively connectable with the controller to transfer to the controller the detected values of said at least one control parameter detected by the sensor.
An 81st aspect according to any one of the preceding aspects, wherein the controller is configured for:
An 82nd aspect according to any one of the preceding aspects, wherein the controller is configured to:
An 83rd The system of any one of the preceding aspects, wherein controller configured to:
An 84th aspect according to aspect 82 or 83, wherein the determined temperature range is between 60 and 115° C. and the certain temperature threshold is at least 80° C.
An 85th aspect according to any one of the preceding aspects 1-84, further comprising a navigation sensor, such as a three-dimensional navigation sensor, or a shape sensor, such as a Fiber Bragg Grating sensor, on at least the distal end region, in particular wherein the navigation sensor is one or more of an electromagnetic sensor, a 3D electromagnetic sensor, shape sensor, FBG sensor, a 3D ultrasound sensor, and an impedance tracking for 3D navigation.
An 86th aspect according to any one of the preceding aspects 7-85, further comprising a perforation element at a distal tip of the flexible shaft configured to advance through a tumor, wherein the perforation element is selected from a list comprising a needle, a deployable needle, and an RF perforation electrode.
An 87th aspect according to any one of the preceding aspects 6-87 in combination with aspect 54, wherein a distance between the space occluder and the ablation element is in a range of 1 mm to 40 mm.
An 88th aspect relates to an ablation catheter comprising:
An 89th aspect according to aspect 88 further comprising at least one space occluder operative at or proximate to the shaft distal end portion, in particular wherein the space occluder is one of a tapered shaft section, a deployable balloon, a deployable valve, or a deployable stent.
A 90th aspect according to aspect 89, wherein the occluder comprises a deployable occlusion balloon having a first cross section width of 1 to 30 mm, a length in a range of 5 to 30 mm, and wherein the occlusion balloon is configured to expand to occlude a portion of the airway.
A 91st aspect according to aspect 90, wherein the first cross section width is at a proximal region of the deployable occlusion balloon, a second cross section width in a range of 1 to 30 mm is at a distal region of the balloon, and a cross section width between the first and second cross section width is less than both the first and second cross section width.
A 92nd aspect according to aspect 90, wherein the first cross section width is at a proximal region of the deployable occlusion balloon, and a second cross section width in a range of 1 to 20 mm and less than the first cross section width is at a distal region of the balloon.
A 93rd aspect according to aspect 88 to 92, comprising a tubular sheath or bronchoscope receiving said shaft, wherein at least the distal end portion of the flexible shaft is configured to emerge from the tubular sheath or bronchoscope.
A 94th aspect according to aspect 93 in combination with aspect 90, wherein the space occluder is carried by the tubular sheath or bronchoscope or wherein the at least one space occluder is directly carried by the shaft or by a different shaft.
A 95th aspect according to any of aspects 88 to 94 in combination with aspect 90, further comprising an inflating lumen extending through the flexible shaft and having a proximal end connectable to a source of a fluid, optionally a source of liquid or a source of gas, and a distal end in fluid communication with inside of the balloon.
A 96th aspect according to any of aspects 88 to 95, wherein the flexible shaft comprises depth markers at least on 5 cm of the proximal region and 5 cm of the distal region.
A 97th aspect according to any of aspects 88 to 96, comprising at least one suction opening at the shaft distal end portion configured to be placed in fluid communication with a vacuum source to aspirate air from a lung volume surrounding the distal end portion of the shaft.
A 98th aspect according to aspect 97 in combination with aspect 90, wherein the at least one suction opening is positioned distal with respect to the space occluder.
A 99th aspect according to aspect 98 comprising an additional space occluder operative at or proximate to the shaft distal end portion, in particular wherein the additional space occluder is one of a deployable balloon, a deployable valve, a deployable stent, a tapered shaft section, and wherein the at least one suction opening is positioned between the space occluder and the additional space occluder.
A 100th aspect according to any of aspects 88 to 99, wherein the at least one conductive fluid outlet is positioned distal with respect to the space occluder or between the space occluder and the additional space occluder.
A 101st aspect according to any of aspects 88 to 100 further comprising at least one sensor positioned distal to the space occluder or between the space occluder and the additional space occluder.
A 102nd aspect according to aspect 101 wherein the at least one sensor is carried by the distal end portion of the flexible shaft and wherein the physical property is of one of temperature, pressure, electric impedance, or electric conductivity of material surrounding the distal end portion of the flexible shaft.
A 103rd aspect according to any of aspects 101 or 102 wherein the at least one sensor comprises a first sensor positioned proximal to the ablation element and a second sensor positioned distal to the ablation element.
A 104th aspect according to any of aspects 88 to 102 wherein the at least one ablation element comprises an ablation element having a rounded distal tip positioned at a distal tip of the flexible shaft.
A 105th aspect according to aspect 97, in combination with any of aspects 88 to 103, comprising:
A 106th aspect according to any of aspects 88 to 105, wherein the flexible shaft has an outer diameter less than 2 mm.
A 107th aspect according to any of aspects 88 to 106, wherein at least a portion of the flexible shaft is capable of turning such that a bend in the shaft has a radius of curvature of at least 7 mm.
A 108th aspect according to any of aspects 88 to 107, wherein the flexible shaft has a length of at least 50 cm.
A 109th aspect according to any of aspects 88 to 108, wherein the elongated shaft has a guidewire lumen in the distal end portion configured to receive a guidewire.
A 110th aspect according to any of aspects 105 and 109, wherein the suction lumen and guidewire lumen are formed by a common lumen.
A 111th aspect according to any of aspects 88 to 110, wherein the ablation element comprises at least one electrode characterized by one or more of the following features:
A 112th aspect according to any of aspects 88 to 111, wherein the at least one ablation element includes at least two electrodes, and wherein a separation between electrodes is between five to fifteen mm.
A 113th aspect according to any of aspects 88 to 112, in combination with aspect 101, including an interface component connectable with said at least one sensor and at least communicatively connectable with a controller to transfer to the controller values of said at least one control parameter detected by the sensor.
A 114th aspect according to any of aspects 88 to 113 in combination with aspect 101, comprising a controller configured for:
A 115th aspect according to any one of aspects 88 to 114, in combination with aspect 101, comprising a controller configured to: receive signals from the at least one sensor, said sensor being a temperature sensor configured to monitor temperature at said target region; and control the conductivity or the composition of the conductive fluid delivered through said at least one outlet based on the monitored temperature to maintain the temperature values detected by the temperature sensor within a determined temperature range or above a certain temperature threshold.
A 116th aspect according to any one of the preceding aspects 88 to 115, wherein the controller is configured to: receive signals from the at least one sensor, said sensor being a temperature sensor, in particular when this aspect depends upon aspect 7 said sensor being configured for detecting values of temperature of material surrounding the distal end portion of the flexible shaft; monitor temperature at the target region; and adjust the ablation energy power output by the energy source to maintain the temperature values detected by the temperature sensor within a determined temperature range or above a certain temperature threshold.
A 117th aspect according to any of aspects 115 or 116, wherein the determined temperature range is between 60 and 115° C. and the certain temperature threshold is at least 80° C.
A 118th aspect according to any one of the preceding aspects 88 to 117, further comprising a navigation sensor, such as a three-dimensional navigation sensor, or a shape sensor, such as a Fiber Bragg Grating sensor, on at least the distal end region, in particular wherein the navigation sensor is one or more of an electromagnetic sensor, a 3D electromagnetic sensor, shape sensor, FBG sensor, a 3D ultrasound sensor, and an impedance tracking for 3D navigation.
A 119th aspect according to any of aspects 88 to 118, further comprising a perforation element at a distal tip of the flexible shaft configured to advance through a tumor, wherein the perforation element is selected from a list comprising a needle, a deployable needle, and an RF perforation electrode.
A 120th aspect according to any of aspects 89 to 119, wherein a distance between the space occluder and the ablation element is in a range of 1 mm to 40 mm.
A 121st aspect according to any of aspects 88 to 120, comprising a tapered distal end, a lumen passing through the shaft from the proximal region to the distal region, wherein the lumen exits the distal region at the narrowest part of the tapered distal end.
A 122nd aspect relates to a system comprising the catheter of aspect 121 and a tumor perforating wire adapted to be advanced through the lumen passing through the shaft from the proximal region to the distal region and beyond the distal region, the tumor perforating wire comprising a sharp distal tip, optionally a depth marker on a proximal region and optionally a radiopaque marker on a distal region.
A 123rd aspect relates to a solution for treatment of lung cancer, in particular non-small cell lung cancer (NSCLC), in a lung airway target region wherein:
A 124th aspect according to aspect 123, wherein said solution is a hypertonic saline solution.
A 125th aspect according to any one of aspects from 123 or 124, wherein said solution has a conductivity, at sea level and 20° C., of at least 30 mS/cm preferably comprised between 70 mS/cm and 225 mS/cm.
A 126th aspect according to any one of the aspects from 123 to 125, wherein the total volume of solution delivered during said total treatment time is comprised between 0.3 ml and 60 ml.
A 127th aspect according to any one of aspects from 123 to 126, wherein delivering the said solution at a non-constant flow rate to the target region comprises alternating intervals in a low delivery mode and intervals in a high delivery mode, wherein during the low delivery mode interval, flow rate is maintained between 0 and 10 ml/min or a bolus quantity is delivered between 0 and 10 ml, and wherein in the high delivery mode interval, flow rate is maintained between 2 and 16 ml/min or a bolus quantity is delivered between 0.3 and 60 ml.
A 128th aspect according to any one of aspects from 123 to 127, wherein delivering the said solution at a non-constant flow rate to the target region comprises maintaining an average flow rate of conductive fluid during said treatment time comprised between 0.1 and 15 ml/min.
A 129th aspect according to any one of aspects from 123 to 128, wherein the hypertonic saline solution is locally delivered to the target region via the airway while delivering RF ablation energy, having a power in a range of 1 to 200 W, in particular comprised between 20 and 200 W.
A 130th according to any one of aspects from 123 to 129, wherein the saline solution includes a reverse phase transition polymer and water, which transitions from a lower viscosity to a higher viscosity when transitioned from below body temperature to body temperature.
A 131st aspect according to any one of aspects from 123 to 130, wherein the said solution composition is delivered to the target region, with the target region of lung sequestered by inflating a first occluding balloon in the natural airway leading to the target region, wherein the balloon is proximal to the target region of lung.
A 132nd aspect according to any one of aspects from 123 to 131, wherein the said solution is delivered to the target region, with the target region of lung sequestered by inflating, a second occluding balloon in the said natural airway distal to the first occluding balloon and distal to the target region.
A 133rd aspect according to any one of aspects from 131 or 132, wherein the said solution is delivered to the target region, while the one or both balloons occlude the natural airway and form a portion of the airway in which the said solution is injected and suppress flow of the liquid outside of that portion of the airway.
A 134th aspect according to any one of aspects from 123 to 133, wherein said solution has a theoretical Osmolarity between 0.8 and 15 Osm/L, preferably between 5 and 9 Osm/L.
A 135th aspect according to any one of aspects 123, or from 125 to 134, wherein said one or more solutes are selected among physiologically acceptable salts and inorganic hydroxides, preferably selected from the group of any of the following aqueous solutions or combinations thereof: calcium chloride, magnesium chloride, sodium carbonate, sodium chloride, sodium citrate, sodium hydroxide, or sodium nitrate.
A 136th aspect according to any one of aspects from 123 to 134, wherein the solution is a hypertonic saline solution which comprises sodium chloride (NaCl) at a concentration of 3% to 30% (w/v) and water.
A 137th aspect according to aspect 136, wherein the solution is a hypertonic saline solution which comprises a sodium chloride (NaCl) at a concentration of between 5% to 25% (w/v).
A 138th aspect according to any one of aspects from 136 or 137, wherein the solution comprises components different from water and sodium chloride at a weight/volume concentration below 1%.
A 139th aspect according to any one of aspects from 123 to 138, wherein the target region is formed by cancer tissue and has a volume of between 0.1 to 30 cm3, in particular from 0.5 to 15 cm3.
A 140th aspect according to any one of aspects from 123 to 139, wherein said solution is used during a procedure with a total treatment time which is function of the volume of the target region.
A 141st aspect according to any one of aspects from 123 to 141, wherein said solution is used during a procedure with a total treatment time of less than 7 minutes and wherein said solution is used for treating a target region of approximately less than 2 cm diameter.
A 142th aspect according to any one of aspects from 123 to 140, wherein said solution is used during a procedure with a total treatment time of less than 10 minutes and wherein said solution is used for treating a target region of approximately 2 cm diameter.
A 143th aspect according to any one of aspects from 123 to 140, wherein said solution is used during a procedure with a total treatment time of less than 15 minutes and wherein said solution is used for treating a target region of at least 2 cm diameter.
A 144th aspect according to any one of aspects from 123 to 140, wherein said solution is used during a procedure with a total treatment time of less than 30 minutes and wherein said solution is used for treating a target region greater than 3 cm diameter.
A 145th aspect according to any one of aspects from 123 to 144, wherein said solution directly contacts the target region.
A 146th aspect according to any one of aspects from 123 to 145, wherein the solution is delivered to the airway target region using the system of any one of the preceding aspects 1 to 87 or using the catheter of any one of the preceding aspects 88 to 122.
A 147th aspect relates to a system for treatment of a target region of lung tissue, the system comprising: a flow regulator configured to be interposed between a conductive fluid source and a conductive fluid outlet positionable at or in proximity of the target region of lung tissue, the flow regulator being further configured to control a flow rate or a bolus quantity of the conductive fluid coming from the fluid source and delivered to the conductive fluid outlet; a controller configured to control the flow regulator and configured to receive values detected by a sensor, wherein the sensor detects values of a control parameter representative of a physical property which is at least one of: temperature (T), pressure (p), electric impedance (Z), and electric conductivity (C) of material present at or in proximity of the target region of lung tissue; wherein the controller is configured to: receive one or more of the values of the control parameter; control the flow regulator based on the one or more of the values of the control parameter, wherein the control the flow regulator comprises executing a control cycle including: controlling the flow regulator in a high delivery mode in which the flow rate of the conductive fluid delivered to the conductive-fluid outlet is no less than a set high flow rate, or the bolus quantity of conductive fluid delivered to the conductive fluid outlet is no less than a set high bolus quantity, and controlling the flow regulator in a low delivery mode in which the flow rate of the conductive fluid delivered to the conductive fluid outlet is no greater than a set low flow rate smaller than the set high flow rate, or the bolus quantity of the conductive fluid delivered to the conductive fluid outlet is no greater than a set low bolus quantity smaller than the set high bolus quantity.
A 168th aspect relates to a method of treating a target region of lung tissue comprising: delivering ablative energy to the target region; delivering conductive fluid to the target region during the delivery of the ablative energy; sensing values of a control parameter that is at least one of a temperature (T), a pressure (P), an electric impedance (Z), and an electric conductivity (C) proximate to the target region, and controlling the delivery of the conductive fluid by: (i) controlling a flow rate or a bolus of the conductive fluid based on the sensed values of the control parameter; (ii) while operating in a high delivery mode, controlling the flow rate to be above a set high flow rate, or controlling the bolus to be above a set high bolus quantity, and (iii) while operating in a low delivery mode, controlling the flow rate to be below a set low flow rate or controlling the bolus to be below a set low bolus quantity, wherein the set low flow rate is lower than the set high flow rate, or the set low bolus quantity is less than the set high bolus quantity.
The present disclosure is directed generally to devices and methods for ablating malignant lung tumors and more particularly to ablating lung tumors with an approach through the patient's airway. An approach through the patient's airway may also be referred to as a transbronchial or endobronchial approach and comprises delivering medical devices through passageways by which air passes through the nose or mouth to the alveoli of the lungs. The term airway refers to any of the anatomical lumens of the respiratory system through which air passes including the trachea, bronchi, and bronchioles.
There are two major types of lung cancer, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Non-small cell lung cancer accounts for about 85 percent of lung cancers and includes: Adenocarcinoma, the most common form of lung cancer in the United States among both men and women, are formed from glandular structures in epithelial tissue and usually forms in peripheral areas of the lung; Squamous cell carcinoma, which accounts for 25 percent of all lung cancers and is more typically centrally located; Large cell carcinoma, which accounts for about 10 percent of NSCLC tumors. The focus of this disclosure is on treating NSCLC, which may occur peripherally among bronchioles, centrally among bronchi, or in lymph nodes. However, the devices, systems and methods disclosed herein may also be used for ablating or treating other diseases of the lung as well.
An aspect of the disclosure provides a method for treating a lung tumor of a patient. A pathway to a point of interest in a lung of a patient is generated. It is anticipated that in the majority of patients with a solitary nodule an airway can be identified on CT leading to the target suitable for positioning of an ablation energy delivery element proximate, for example within 1 cm, of the target. Using a pre-acquired CT as a map a flexible instrument can be threaded through the airways by a bronchoscopist using known and existing tools. In one embodiment, an extended working channel is advanced through the airway into the lung and along the pathway to the point of interest. The extended working channel is positioned in a substantially fixed orientation at the point of interest. Anchoring mechanisms may be used to secure stability of the channel. A catheter may be advanced though the extended working channel to the targeted region of the lung. A working channel may be for example a lumen through a delivery sheath or through a bronchoscope, both of which may be steerable or incorporate a guidewire lumen. Optionally, a delivery sheath may be an endobronchial ultrasound delivery sheath that generates and ultrasound image of tissue around the distal end of the sheath. A portion of the lung containing the targeted region may be occluded and at least having its corresponding air volume reduced, for example by occluding an airway feeding the portion (e.g., using at least an occluding element such as a balloon on the catheter or delivery sheath) and applying negative pressure to the lung portion or other means for collapsing a portion of lung disclosed herein. To confirm air volume reduction in the portion of lung, electrodes on the catheter may be used to measure tissue impedance or phase. A complete collapse of the targeted lung portion is not necessary. Experimental observations show that an air volume reduction in the targeted lung portion, which produces a 5 to 20% decrease in the respective bipolar impedance, is sufficient for the purpose of facilitating effective ablation energy delivery. The lung tissue is treated with the ablation catheter at the targeted region of the lung by injecting hypertonic saline, or other types of biocompatible conductive salts or solutions (e.g. calcium chloride, magnesium chloride, sodium carbonate, sodium chloride, sodium citrate, sodium hydroxide, or sodium nitrate, etc.), through the catheter in to the targeted portion of lung and applying RF energy from one or more electrodes on the catheter. Optionally, more than one ablation catheter may be delivered to the targeted region of lung and an RF circuit may be made between electrode(s) on a first catheter to electrode(s) on a second catheter. In the presented embodiments of this disclosure RF electrodes are used to deliver ablation energy.
An extended working channel may be positioned within a patient, optionally through a bronchoscope or as part of a bronchoscope. A locatable guide may be positioned within the extended working channel for positioning the extended working channel to the point of interest. Biopsy tools may be advanced to the point of interest. Prior to advancing the biopsy tool through the extended working channel, the locatable guide may be removed from the extended working channel. Alternatively, navigation-guided extended working channels may be used in conjunction with 3-D navigation systems, such those offered by Veran Medical or superDimension™ (Medtronic), or robotically delivered bronchoscopic working channels may be used, such as those offered by Intuitive Surgical or Auris Health. For example, the navigated instrument (e.g. the catheter of this disclosure) may be fitted with shape sensors, such as Fiber Bragg Grating (FBG) sensors. The use of such shape sensors inside ablation catheters is described in “FBG Sensor for Contact Level Monitoring and Prediction of Perforation in Cardiac Ablation” by Ho et al. Sensors 2012, 12, 1002-1013, incorporated herein by reference. The lung tissue may be biopsied. If the biopsy is confirmed positive, then the lung tissue may be ablated. The biopsy tool is retracted and replaced with an ablation catheter or tool comprising at least one energy delivery element. This method may facilitate positioning of the energy delivery elements of the ablation catheter or tool at the same place where the biopsy is taken. Prior to treating the lung tissue, the placement of the ablation catheter at the point of interest may be confirmed, for example visually using a bronchoscope and identifying the point of interest with respect to elements of the airway. The lung tissue or tumor may be penetrated at the point of interest. Effective treatment of the lung tissue may be confirmed, for example by obtaining a post ablation biopsy or assessing the impedance or phase of the treated tissue using electrodes or sensors on the ablation catheter.
With the current resolution of CT scanners, at least seven or eight, likely more, generations of airways can be imaged and evaluated. There are reasons to believe that the imaging resolution will rapidly improve further. If the trachea is the beginning point and if a pulmonary parenchymal nodule is the targeted end-point, then appropriate software can interrogate the three-dimensional image data set and provide a pathway or several pathways through the adjacent airways to the target. The bronchoscopist can follow this pathway during a real or navigational bronchoscopy procedure and the correct airway pathway to the nodule can be quickly cannulated using a wire, a bronchoscope and a thin wall polymer tube or channel or sensed/navigational bronchoscopy instruments.
Once the access channel is in place, then multiple probes can be placed either to biopsy, or to ablate the identified tumor. Ultrathin bronchoscopes can be used in a similar manner. In conjunction with navigational bronchoscopy tools, using these sorts of approaches, majority of peripheral lung lesions can be destroyed.
Currently available fiberoptic bronchoscopes (FOBs) have an illumination fiberoptic bundle and imaging fiberoptics or a camera. Except for the very few “ultrathin” bronchoscopes, there is also a channel for suction of secretions and blood, for the passage of topical medication and fluid for washing, and for the passage of various instruments for diagnostic retrieval of tissues or for therapeutic procedures. A typical diagnostic bronchoscope has an outer diameter of 5.0 to 5.5 mm and an operating channel of 2.0 to 2.2 mm. This caliber channel admits most cytology brushes, bronchial biopsy forceps, and transbronchial aspiration needles with sheathed outer diameters between 1.8 and 2.0 mm Smaller bronchoscopes, in the range of 3.0 to 4.0 mm at the outer diameter and correspondingly smaller channels, are usually given a “P” designation (for pediatrics), but they can be used in the adult airways. Newer generations of slim video and fiberoptic bronchoscopes have a 2.0 mm operating channel with a 4.0 mm outer diameter. The one disadvantage of these bronchoscopes is the sacrifice of a smaller image area because of fewer optical bundles. The ultrathin bronchoscopes generally have outer diameters smaller than 3 mm. For example, Olympus models BF-XP40 and BF-XP160F (Olympus America, Center Valley, PA) have outer diameters of 2.8 mm and operating channels of 1.2 mm Special instruments (e.g., reusable cytology brush and forceps) of the proper calibre are available for tissue sampling. Current generations of video bronchoscopes are all built with a 60 cm working length. These bronchoscopes are suitable for accessing distal airways to place the guide wire over which a delivery channel or an energy delivery catheter can be exchanged.
Navigation bronchoscopy (NB) consists of two primary phases: planning and navigation. In the planning phase previously acquired CT scans are utilized to mark and plan pathways to targets within the lung. In the navigation phase, these previously planned targets and pathways are displayed and can be utilized for navigation and access deep within the lung. Upon arriving at the target NB enables multiple applications all within the same procedure. CT scans of the patient's chest are loaded into proprietary software that reconstructs the patient's airways in multiple 3D images. The physician utilizes these images to mark target locations and plan pathways to these target locations within the lungs. Using the planned pathway created in the planning phase and real-time guidance, the physician navigates a sensed probe and extended working channel to the desired target location(s). Once at the desired location, the physician locks the extended working channel in place and the sensed probe is removed. The extended working channel provides access to the target nodule for bronchoscopic tools or catheters.
Reducing Air Volume in a Portion of Targeted Lung Tissue
The lungs are divided into five lobes as shown in
Lung compliance is an important characteristic of the lung. Different pathologies affect compliance. Particularly relevant to cancer ablation are the observations that: fibrosis is associated with a decrease in pulmonary compliance; emphysema/COPD may be associated with an increase in pulmonary compliance due to the loss of alveolar and elastic tissue; and pulmonary surfactant increases compliance by decreasing the surface tension of water. The internal surface of the alveolus is covered with a thin coat of fluid. The water in this fluid has a high surface tension and provides a force that could collapse the alveolus. The presence of surfactant in this fluid breaks up the surface tension of water, making it less likely that the alveolus can collapse inward. If the alveolus were to collapse, a substantial force would be required to open it, meaning that compliance would decrease drastically. Atelectasis, clinically defined as collapse of the lung area visible on X-ray, is generally not desired. However, localized lung collapse can be beneficial in the treatment of emphysema and, as the authors propose, targeted lung cancer ablation. Advantages to collapsing or air volume reducing the targeted lung portion that contains a targeted tumor during tumor ablation may include the following: electrodes positioned in airways surrounding the tumor may be drawn closer to the tumor, thereby improving concentration of ablative energy or increasing efficacy of ablating the tumor; air will be removed from the collapsed, or shrunk lung tissue supplied by the airway making the delivery of ablative energy and the thermal propagation more efficient; collapse of the segment may lead to hypoxia that provoke regional hypoxic pulmonary vasoconstriction and ischemia of the lung segment which reduces metabolic cooling and improves efficient utilization of the thermal energy; the spread of irrigation fluid, such as hypertonic saline, may be confined to the targeted area, thereby providing virtual-electrode ablation outcomes mostly to the target region. However, complete lung, lung lobe or lung segment collapse is not necessary for the intent of this invention. Bronchial air volume reduction via vacuum application to the catheter is, typically, sufficient in improving the electrical contact between the RF electrode and the bronchial wall. This, in turn, increases the safety and reduces the ineffectiveness of energy delivery which may be caused by evaporation of irrigation fluid (caused by overheating) or by its inadvertent spread to neighboring tissues; and electrode contact with tissue may be more consistent or have greater surface area of contact. Furthermore, ablative energy such as radiofrequency electrical energy may be delivered by a computer-controlled ablation console and collapsing the lung portion may improve temperature-controlled ablation performance by increasing contact stability and pressure between the tissue and electrode(s). For example, in a collapsed or shrunk airway, temperature sensor(s) positioned in or on the electrode(s) may provide more accurate temperature feedback to the computer-controlled ablation console used to control the energy delivery parameters such as RF power, RF power ramp up slope, or duration, while increased contact stability and pressure may allow increased stability of thermal and electrical conduction allowing the temperature sensor(s) to have a more accurate representation of temperature of the tissue around the electrode. Consequently, the ablative energy delivered to the targeted lung tissue and tumor may be optimized and the temperature of the targeted tissue may be heated to an intended temperature set point in an effective and safe manner.
Air volume reduction in one lobe or a segment or other section of a lung defined by morphology of airways and air supply by airways can be impeded by collateral interlobular ventilation that is common in patients with incomplete interlobar fissures and partially damaged and destroyed lung. Alternative methods of segmental or lobar collapse can be employed by heating lung tissue or injecting chemicals, foam or hot steam into the targeted segment or the targeted lobe. For example, injection of hot steam into a contained space like lobe or segment results in collapsing the space. The nature of the lung is such that when a segment is collapsed, pressurized adjacent segments compress it and fill the volume vacated by the collapsed space. Techniques for collapsing or partially collapsing portion of the lung that has collateral air pathways using a bronchoscope and bronchoscope delivered tools are described for example in U.S. Pat. No. 7,412,977 B2. Partial lung collapse, particularly of an upper lobe, was previously proposed to imitate results of lung reduction surgery in advanced emphysema but has not been suggested to enhance thermal ablation (e.g. RF) of tumors. Techniques proposed included: occluders and valves, steam (e.g., thermal), foam, and glue injection into airways. Mechanical compression of a lung portion using springs or wire coils was proposed also. All these methods can be envisioned as being modified and adopted for cancer therapy in any lobe or segment where the tumor was located on CT and identified as malignant. As mentioned above, partial lung or lung region collapse is not required to implement successfully the present invention. The goal is to reduce bronchial air volume so to enhance electrode-tissue contact.
Ultimately an entire lung can be temporarily collapsed using a technique of independent lung ventilation. Lungs are intubated and ventilated by separate endotracheal tubes with obturators of the two main bronchi. A patient that is healthy enough to tolerate it can breathe using mechanical ventilation of only one lung while the contralateral lung is being collapsed and operated on. Electrodes can be positioned prior to deflating and collapsing the lung. In this case collateral ventilation will not have much effect on the ability of the operator to collapse the lung.
Reducing the air volume of a portion of targeted lung may provide other advantages that facilitate tumor ablation by enhancing RF ablation lesion dimensions. Air in the lung's airway is a very poor thermal conductor and electrical conductor. Collapsing the airways (e.g., by occluding airflow or with other methods described herein) deflates them, which enhances the permeability of RF through the previously aerated tissue. We therefore propose reducing the air volume in a target lung portion as a means to facilitate improved energy delivery through electrodes combined with a device such as an endobronchial catheter. A balloon (e.g., filled with liquid or air), another space occluder, a deployable valve, injected steam, a fan, glue injection, or stent could be used to occlude the airway to reduce the air volume of a specific lung portion encompassing or next to the targeted tumor. The balloon, for example, may be used to occlude a portion of the airway and as the airway is blocked, the blood absorbs the gas inside the alveoli thus reducing the air volume. Alternatively, the entrapped air may be sucked out using vacuum pressure through a lumen in the catheter. The suction may be applied for 30 s to 10 min, depending on the level of shrinkage or collapse desired. If the airway is deprived of air the alveoli shrink. In some cases, blood, fluids and mucus may fill, at least partially, the previously aerated space, allowing the space to conduct RF energy and heat more effectively.
In addition, collapse of the segment leads to hypoxia that leads to regional hypoxic vasoconstriction of the lung. Reduced blood flow to the targeted region of the lung results in less blood velocity and metabolic cooling and more efficient utilization of the thermal energy.
A procedural method of ablating a lung tumor comprising collapsing a targeted portion of the lung with a catheter configured to occlude an airway and ablate tissue may comprise the following steps: identifying the location of a targeted tumor in a lung (e.g., using medical imaging technology such as CT); Generating a 3D navigation map by registering the medical images with navigation technology; delivering a bronchoscope through the patient's airway placing the distal end in a vicinity of the targeted lung portion optionally using 3D navigation or electromagnetic navigation assistance; taking a biopsy to confirm tumor position; lubricate the bronchoscope, occlusion-ablation catheter and endotracheal tube lumen; placing the occlusion-ablation catheter through the bronchoscope working channel; steering the catheter's distal region to the targeted site navigating (e.g. by standard, virtual or navigation bronchoscopy) the ablation electrode as close to the tumor as possible optionally comprising delivering the catheter over a guidewire; optionally confirming electrode position or contact using impedance measured from the electrode, imaging or EM navigation; optionally positioning the occlusion balloon in the airway proximal to the ablation site; inflating the occlusion balloon while visualizing with the bronchoscope's lens; optionally allowing air volume reduction in the targeted portion of lung as air is absorbed or apply other bronchial air volume reduction steps as disclosed herein (e.g., apply suction to remove air from the targeted lung portion); optionally monitoring electrical impedance of tissue (e.g., between the RF electrode(s) and a grounding pad, or between bipolar RF electrodes) wherein a stable, consistent impedance indicates the bronchial air volume has been reduced, thus making greater tissue contact with the electrode(s) (e.g., in a study conducted by the authors impedance dropped about 24% to 38% when the bronchial air volume was reduced); irrigating the electrode(s) or infusing conductive fluid into the targeted lung portion; delivering computer-controlled ablation energy through the electrode(s) to the targeted tissue; optionally removing fluid remaining in the lung portion through the catheter, or through a bronchoscope; deflating the occlusion balloon and removing the catheter from the patient; visualizing the treated airway for signs of hemorrhage or blistering, which may be treated if required. Optionally, subsequent ablations may be made at different locations by moving the ablation electrode to the subsequent location. If previously collapsed, it may be necessary to let the lung portion inflate before moving the ablation electrode if it is difficult to relocate the electrode while the lung portion is collapsed. In some situations, it may be possible to keep the lung portion deflated and optionally infused with conductive fluid while relocating the electrode(s). Optionally, fiduciary markers may be placed in or around the tumor to later locate the tumor using CT to determine if it was successfully ablated or to apply a subsequent ablation.
Delivery of Conductive Fluid into the Targeted Lung Portion
Conductive fluid may be delivered (e.g., via a lumen of an ablation catheter) to the airway in the targeted portion of lung to enhance RF ablation. The delivery of conductive fluid may be a volume infusion of hypertonic saline (e.g., hypertonic saline having concentrations in a range of 5% to 30%) to enhance endobronchial lung tumor ablation by ablating a larger volume of tissue (e.g., ablations greater than or equal to 1.5 cm in diameter). Other conductive fluids may be used. For example, several biocompatible aqueous conductive solutions (e.g., conductive solutions that are not per se lethal or toxic to the living body) such as calcium chloride, magnesium chloride, or sodium hydroxide may be used. Such solutions, in by-volume concentrations of 10% or higher, have an electrical resistivity in the range of 2-35 Ω·cm, preferably in the range of 4-14 Ω·cm (70-225 mS/cm if expressed as conductivity), low enough to support effective conduction of radiofrequency current. Osmolarity is an important characteristic of such aqueous solutions, which can be computed as:
Higher-osmolarity solutions may be preferred. In the calculation of the theoretical osmolarity of the saline solution the osmotic coefficient φ is =1
Optionally, a conductive fluid may have a high viscosity or may be injected in a low viscosity state to a target region and transition to a higher viscosity state in the targeted region of the body. For example, ionic salts such as NaCl or others, such as those listed above, may be mixed with a reverse phase transition polymer and water, which may transition to higher viscosity when transitioned from below body temperature to body temperature. The polymer with appropriate characteristics may be one such as a block-co-polymer PLGA-PEG-PLGA consisting of polyethylene glycol, which is covalently esterified by an FDA-approved poly lactic-co-glycolic acid on both ends. Other examples of polymers may be based on polyethylene glycol, albumin, silk, wool, chitosan, alginate, pectin, DNA, cellulose, polysialic acids, dendritic polylysine, poly (lactic-co-glycolic) acid (PLGA), gellan, polysaccharides and poly-aspartic acid, and combinations thereof. The mixture may be designed to preserve the high electrical conductivity of the hypertonic saline base, while adding the higher viscosity properties of the polymer. This way, better control can be asserted over the spread of the conductive fluid. The polymer may be biodegradable, biocompatible or bioabsorbable. The ionic component may include for example, M.sup.+X.sup.− or M.sup.2+Y.sup.2−, where M belongs to alkaline or alkaline earth metal such as Li, Na, K, Rb, Cs and X represents halogens, acetate and other equivalent counter balance to M.sup.+, and Y can be X.sub.2 or mixed halogens, acetates, carbonate, sulfate, phosphate and other equivalent counter balance to M.sup.2+, as well as formic acid, glycolic acid, lactic acid, propionic acid, caproic acid, oxalic acid, malic acid, citric acid, benzoic acid, uric acid and their corresponding conjugate bases. A conductive fluid may further comprise ingredients such as pharmaceutical agents (e.g., anticancer or antibiotic) to aid tissue healing or further treatment of cancerous cells, or radiopaque contrast. The volume infused may be sufficient to infuse beyond the targeted airway and in to the alveoli and lung parenchyma. This is achieved by conducting the delivered ablation energy (e.g., RF or microwave) to more tissue than the surface of the electrode contacts, thus, in effect, increasing the effective electrode size (i.e. creating a virtual electrode) and creating more stable and consistent electrical contact with the tissue. A conductive fluid, such as hypertonic saline, or others listed above, may also make ablation energy delivery more efficient, as less power is lost in saline and more delivered to the tissue. Less power is lost into hypertonic saline compared to physiological saline because hypertonic saline has a significantly increased electrical conductivity, and therefore lower contact impedance. With less power being lost into hypertonic saline, the boiling point is less likely to be reached. Therefore, ablations produced with hypertonic saline in a lung portion with reduced bronchial air volume tend to not show char formation and yet produce larger lesions. Injection of conductive fluid may be done with methods and devices as described herein for injection and optional concomitant retraction of fluid and optionally with collapsing of the targeted lung portion around the electrode(s). An example of a device 220 configured to occlude the targeted portion of lung to collapse the lung portion and ablate with an irrigated electrode is shown in
Animal experiments have shown a combination of infusing hypertonic saline into an airway and delivering thermal energy to the airway by way of radiofrequency has an impressive effect of killing tissue as seen on CT scans taken 2 weeks following the procedure. Some previous studies have shown that hypertonic saline could significantly attenuate tumor cell adhesion to endothelium by inhibiting adhesion molecule and laminin expression. (Shields C J1, Winter D C, Wang J H, Andrews E, Laug W E, Redmond H P. Department of Academic Surgery, Cork University Hospital and National University of Ireland, Wilton. Hypertonic saline impedes tumor cell-endothelial cell interaction by reducing adhesion molecule and laminin expression. Surgery. 2004 July; 136(1):76-83.) This may halt the metastatic behavior of tumor cells shed at surgery. Other researches have reported similar studies of using saline to trigger cell apoptosis. The researchers had a study of using salt to kill cancer cells. They have created a technique which can cause cancer cells to self-destruct by injecting them with salt. (Busschaert, N., Park, S., Baek, K., Choi, Y., Park, J., Howe, E., Hiscock, J., Karagiannidis, L., Marques, I., Felix, V., et al (2017). A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations. Nature Chemistry, 9(7), 667-675.) (Ko, S., Kim, S, Share, A., Lynch, V., Park, J., Namkung, W., Van Rossom, W., Busschaert, N., Gale, P., et al (2014). Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells. Nature Chemistry, 6(10), 885-892.) Unfortunately, when a cell becomes cancerous, it changes the way it transports ions across its cell membrane in a way that blocks apoptosis. However, it should be expected that increasing temperature can increase diffusivity of hypertonic saline (HTS) and thus the ability to transport HTS into the cells, and it could be a highly potential direction that the infusing of heated HTS or other salines may have beneficial effect of killing tumor cells. As discussed above, other biocompatible, conductive, aqueous solutions may be employed. A higher osmolarity will support better diffusivity of ions across cellular membranes.
Hot hypertonic saline (HTS), or any other hot solution from those discussed above, has better performances in the osmosis or diffusion to transport HTS with respect to cells, and can increase promotion of cell dehydration. The increased extra-cellular salinity results in loss of water content from within neighboring cells. As a consequence, the hot HTS bolsters the cell desiccation effects produced by the delivery of RF energy. Comparatively, a study done with a standard, off-the-shelf ablation catheter (ThermoCool) powered at 50 W and irrigated with room-temperature saline, at high irrigation rates (30 ml/min), resulted in much less cell death. The HTS with a concentration above 5%, for example 10%, can be infused to the target space and then, as RF currents travel through it into tissue, reaches up to certain temperatures, for example in a range of 60° C. to 115° C., by the electrodes located on the distal area of the catheter. Alternatively, the sequestered portion of the lung can be irrigated with heated HTS from the irrigation port on the catheter directly. The sequestered portion can be exposed to heat and HTS for a duration of at least 2 minutes, or for a duration in a range of 30 seconds to 30 minutes accordingly, after which the HTS and the local area can be cooled down by shutting down the electrodes, irrigating or replacing with room temperature saline, or evacuated from the irrigation port directly. The procedure can be repeated until desired ablation results are achieved. It should be expected that increasing temperature can increase diffusivity of HTS and thus the ability to transport HTS into the cells, and it could be a highly potential direction that the infusing of heated HTS or other salines may have beneficial effect of killing tumor cells.
The composition of the conductive fluid, e.g., HTS, may be adjustable such that electrical or thermal conductivity or viscosity of the HTS may be adjusted. For example, a conductive fluid source may comprise multiple sources that may be combined to adjust properties of the conductive fluid that is injected into the target region of the lung. A software driven controller may be programmed to mix a predetermined or automatically determined ratio of the multiple sources before or during injection of the combined fluids into a natural airway of the lung at the target region to be ablated. For example, separate pumps may be activated at a controlled rate and duration to selectively take a desired amount of each of the multiple sources. The multiple fluids may be pumped to a mixing chamber prior to delivering the combined fluid through the device to the target region, or they may be concurrently or sequentially delivered directly to the target region. Automatic determination of a ratio of multiple sources may be calculated by the controller using input from sensors, for example located on the distal region of the device.
Alternatively, multiple sources of fluids having different properties, such as saline with different salinity, may be provided and a controller may select which source to draw from for irrigation without mixing the solutions. The controller may select a source of fluid based on time within an ablation procedure or total cumulative volume of a fluid delivered to a patient or feedback from sensors such as impedance or temperature. In one example, a first source may contain hypertonic saline (e.g., saline with a salinity above 10%, above 15%, above 20%, about 23.4%) and a second source may contain saline with a lower salinity (e.g., 0.9%). The first source may be drawn from to irrigate the target lung space during an initial period of an ablation procedure and the second source may be drawn from to irrigate during a second period of the ablation procedure. The rationale is that hypertonic saline may be irrigated to get the ablation started and to prime the environment in the target lung space for electrical conductivity, however due to its high salinity it may cause edema in the lung. Too much edema is undesirable. After a first period of irrigated ablation (e.g., up to 2 minutes, up to 2.5 minutes, up to 25% of a total ablation duration) the tissue environment should be prepared enough that a lower salinity saline could be able to do the job of temperature regulation without having the drawback of causing a lot of edema. Optionally, the controller may detect if the conductivity is reduced by the lower salinity saline to a predefined level, for example via impedance measurement, and switch back to the higher salinity saline.
Optionally, the controller may adjust ablation energy delivery parameters (e.g., flow rate of conductive fluid, ablation energy power, set temperature, ramp rate, duration) based on varying properties of the conductive fluid such as conductivity, viscosity, temperature, or pressure. For example, adjusting at least one of the flow rate or the conductivity of the conductive fluid may include adjusting at least one of the flow rate or the conductivity to maintain the values detected by a temperature sensor within a determined temperature range, optionally wherein the determined temperature range is between 60 and 115° C., or above a certain temperature threshold, optionally wherein the preferred temperature threshold is 75-105° C., for example between 85-99° C. In another example, a system is configured to adjust the conductivity of the conductive fluid in the range between 10 mS/cm and 450 mS/cm at a reference fluid temperature of 25° C.
For example, as shown in Table 1, a 6 min delivery of RF power, at an average of 67 W, resulted in an average tissue temperature of 90° C. and an ablation volume of 4.4 cm×3.1 cm×3.9 cm, approximately 27 cm3. Furthermore, hypertonic saline, or any other aqueous solutions from those discussed above (e.g. calcium chloride, magnesium chloride, sodium hydroxide, etc.), is known to be toxic to cancer cells and can alternatively or additionally chemically ablate tumor cells. The permeated saline in lung parenchyma may replace the alveolar air and spread to the surrounding alveoli through Kohn's pores and Lambert's ducts. Perfused hypertonic saline could be doped with nonionic iodinated contrast agent to render it visible on computed tomography (CT). Other conductive irrigation fluids could be imagined such as aluminum sulfate. Creating a flow of the conductive fluid with the use of suction during ablation to continuously replenish irrigation sitting in the ablation zone could further facilitate tumor ablation by removing heat generated in the fluid.
Different liquids can be mixed under computer control to create controllable, programmable and predictable concentration of conductive ions. Alternatively, a non-flowing conductive fluid pooled in the targeted lung tissue could facilitate production of a lesion sufficient to ablate a targeted lung tumor. A desired ablation volume, which may be for example a function of tumor size, distance between the targeted tumor and RF electrodes, or proximity to vulnerable non-target structures, may determine if infusion of a conductive fluid is flowing or stagnant, wherein stagnant infusion may be used for smaller ablations and flowing infusion may be used for larger ablations and optionally a greater flow rate or cooling of injected liquid may be used for even larger ablations.
Conductive fluid can be infused before the start of ablation to prepare the lung for ablation and allow for the fluid to flow into the tissue. Delivering conductive fluid such as hypertonic saline may allow the ablation energy console to operate at a wider range of power levels as necessary to achieve therapeutic goals.
Optionally, a conductive fluid may be injected through a needle catheter positioned in an airway into the parenchyma or tumor, which may deliver the conductive fluid to the target site more effectively or more selectively. The needle may further comprise an RF electrode with an associated temperature and impedance sensor that may be used to deliver RF energy directly to the parenchyma near the tumor or inside the tumor.
Optionally, the conductive fluid such as hypertonic saline solution infusion may be titrated to adjust the size of ablation. As discussed above, hypertonic saline flow rates between 0.2 to 5 ml/min are expected to contribute to the formation of sufficiently large ablation volume, while keeping the patient's electrolytes, blood pressure and fluid loading within normal and safe ranges. Titration may be done by adjusting the saline concentration, the volume of hypertonic saline infused, or by adjusting the position of the occluding structure to block off a different size of lung portion. A higher saline concentration is more electrically conductive and may generate a larger lesion. A greater volume of infused saline may spread to a greater volume of tissue creating a larger lesion. A larger portion of lung that is occluded may accept a larger amount of infused hypertonic saline, which may result in a larger lesion. RF delivery parameters may be adjusted in accordance with hypertonic saline titration. For example, salinity of irrigation fluid may be increased in response to undesired fluctuations in impedance values.
An example of a device 220 configured to be delivered through a working channel, occlude a targeted portion of lung, reduce air volume in the targeted portion of lung, deliver conductive solution into the targeted portion of lung, monitor tissue properties, and ablate a tumor is shown in
The device 220 has an elongated shaft 229 having a proximal region intended to remain outside the patient's body and a distal region 215 intended to be delivered through a working channel to a target region of a lung proximal to a targeted lung tumor. The distal region 215 is configured to be delivered through a working channel (e.g., working channel 225 of a bronchoscope 221 or a lumen of a sheath 213 that may be delivered through the working channel of a bronchoscope). For example, a common bronchoscope working channel may have an inner diameter of 2.8 mm and a length of 60 cm. A delivery sheath 213 adapted for delivery through a 2.8 mm bronchoscope working channel may have an outer diameter less than 2.8 mm, preferably about 1.95 mm+/−0.05 mm, an inner diameter approximately 0.45 mm less than the outer diameter, preferably about 1.5 mm+/−0.05 mm, and a length greater than the brochoscope's length (e.g., greater than 60 cm, preferably about 105 cm). Other dimensions may be applicable for similar catheters adapted to fit through different sized bronchoscope working channels. In its delivery state a device 220 may have a maximum diameter smaller than the inner diameter of the sheath 213 through which it is delivered, for example less than or equal to 2 mm (e.g., less than or equal to 1.5 mm, preferably 1.4 mm+/−0.05 mm). The device 220 may have a length greater than the length of the delivery sheath, for example greater than or equal to 50 cm (e.g., greater than or equal to 60 cm, greater than or equal to 105 cm, preferably about 127 cm). The Shaft 229 of the device 220 may be made for example from an elongate tube of Pebax 720 having an outer diameter of about 1.35 mm. The shaft may be a flexible shaft capable of traversing a bend such that a bend in the shaft has a radius of curvature of as little as 7 mm. The shaft may contain a wire braid to provide flexible, pushable, kink resistant, and torquable functions.
Optionally, the device 220 may have a guidewire lumen 236 (e.g., a polyimide tube with an inner diameter of 0.015″ running through a lumen in the shaft 229) so the device may be delivered over a guidewire 227 or so a component such as a stiffening wire or tumor perforating wire or fiberoptic wire or other device can be delivered through the lumen.
Alternatively, as shown in
Alternatively, a shaft-stiffening wire may be advanced through a lumen in the shaft, for example a guidewire lumen 236, to increase stiffness of the catheter during positioning. The catheter shaft may be quite flexible so it can pass over an airway bend with a radius of curvature as little as 7 mm but may require more stiffness at times when advancing to avoid kinking.
Optionally, the sheath 213 may have depth markers 415 positioned along its length or portion of its length (e.g., at least on the proximal 5 cm and distal 5 cm of the sheath length) and spaced at regular intervals (e.g., spaced at 1 cm center to center with a width of about 1 mm). Optionally, the shaft 229 of the embodiment shown in
The device 220 is configured to temporarily at least partially occlude an airway that feeds the targeted lung portion. As shown in
The obturator 231 shown in
Alternatively, inflatable balloon obturators of any embodiments disclosed herein may be somewhat tapered like the balloon 408 shown in
Another alternative embodiment of an occlusion balloon 423 as shown in
Alternatively, the occlusion balloon 231 may be a different form of occlusion structure such as a deployable valve, or a deployable stent with an occluding material such as PTFE.
The device 220 shown in
As shown in
Hypertonic saline (HTS) refers to any saline solution with a concentration of sodium chloride (NaCl) higher than physiologic (0.9%). Commonly used preparations include 2%, 3%, 5%, 7%, and 23% NaCl and are generally available in sterile bags or bottles through the hospital pharmacy. It is used in medical practice for its osmotic, rather than conductive qualities (e.g. to reduce edema). As discussed, other aqueous solutions can be used (e.g. calcium chloride, magnesium chloride, sodium hydroxide, etc.).
Conductive fluid (e.g., 3% to 30% hypertonic saline) may be delivered to the targeted lung portion through irrigation ports 235 in the electrode(s) 234 or additionally or alternatively through an infusion lumen (not shown) exiting the device 220 distal to the occlusion balloon 231 that may or may not exit through ports in an electrode. The infusion lumen runs from the irrigation ports (e.g., 235) through the shaft 229 to the proximal region of the device where it is connectable to a conductive fluid supply and optionally pump. Alternatively, the guidewire lumen 236 may be used to infuse the conductive fluid.
Alternatively, or additionally in combination with collapsing a targeted portion of lung, the previously aerated space may be infused with an electrically conductive fluid such as hypertonic. Use of hypertonic saline may enhance RF delivery based on the virtual electrode effect.
While the targeted lung portion is occluded with the obturator 231, optionally collapsed, and infused with conductive liquid, RF ablation energy may be delivered from an energy delivery console to the distal electrode 234. A temperature sensor 242 (e.g., T-Type thermocouple) may be positioned on or in the distal electrode 234 and be connected to thermocouple wire 243 running through the shaft 229 to the proximal region of the device 220 where it is connectable to an energy delivery console. The temperature sensor 242 may be used to monitor electrode 234 temperature during energy delivery in which it is used as a parameter to control energy delivery (e.g., temperature controlled power delivery to meet a set point temperature in a range of 45° C. to 115° C., preferably between 50° C. and 95° C., or constant power controlled power delivery with a maximum temperature in a range of 45° C. to 115° C., preferably between 50 to 95° C., depending on specific local conditions to avoid over heating).
As shown in
A return electrode to complete the electrical circuit may be a dispersive electrode positioned on the patient's skin wherein the RF energy conducts through tissue between the distal electrode 234 and the dispersive electrode. Optionally or alternatively, the proximal electrode 237 may also be used to delivery ablation energy or to complete the electrical circuit (e.g., bipolar mode).
As shown in
Alternatively or additionally, a fiberoptic lens may be positioned on the elongated shaft 229 distal to the occlusion structure, which may be used to visualize the airway distal to the occlusion structure. This may facilitate for example confirmation of airway shrinking, position of the electrode(s), or injury to the airway while the occlusion structure is deployed.
Optionally, if the electrode is irrigated by injecting fluid through ports 235 the fluid may be retracted by applying suction to the guidewire lumen 236 to create a flow of fluid.
An expandable occlusion element such as the occlusion balloon 231 shown in
Alternatively, as shown in
Alternatively, the occlusion balloon 431 or 481 may be a different form of occlusion structure such as a deployable valve, or a deployable stent with an occluding material such as PTFE.
Conductive fluid (e.g., 5 to 30% hypertonic saline) may be delivered to the targeted lung portion through irrigation ports 435 in the electrode 434 or additionally or alternatively through an infusion lumen (not shown) exiting the device 420 distal to the occlusion balloon 431 that may or may not exit through ports in an electrode. The infusion lumen runs from the irrigation ports (e.g., 435) through the shaft 429 to the proximal region of the device where it is connectable to a conductive fluid supply and optionally pump.
As shown in
Optionally, as shown in
The second shaft 230 comprises a lumen 583 (e.g., a polyimide tube with an inner diameter of 0.015″ running through a lumen in the second shaft 230) with the corresponding ports 582 positioned in the obturators 581 for inflating and deflating the obturators. The obturator 581 may be a balloon (e.g., compliant balloon) sized to occlude the airway or a range of airway diameters (e.g., diameters in a range of 3 mm to 10 mm).
Conductive fluid (e.g., 5 to 30% hypertonic saline) may be delivered to the targeted lung portion through irrigation ports 535 in the electrode 534 or additionally or alternatively through an infusion lumen (not shown) exiting the device 520 distal to the occlusion balloon 531 that may or may not exit through ports in an electrode. The infusion lumen runs from the irrigation ports (e.g., 535) through the second shaft 230 to the proximal region of the device where it is connectable to a conductive fluid supply and optionally pump.
A telescopic or adjustable distance between the proximal balloon and the electrode(s), or between the proximal balloon and the distal balloon, may advantageously allow placement of the electrode next to the tumor and placement of the occluding balloons at a desired position, which may depend on the geometry of the airway, the size of targeted lung portion, or the size of tumor. Especially, the adjustable distance between the proximal obturator and the distal obturator allows a more specific segment of an airway to be isolated, so any risk or unwanted influence related to the operations, such as air evacuation, fluid infusion or ablation, will be significantly reduced or minimized Optionally, the second shaft 230 may be deflectable or rotatable with respect to the first shaft 529. The ablation electrode(s) 534 may optionally comprise at least one irrigation port 535 for irrigating the electrode.
The dual obturator structure may provide some further advantages such as the following:
Using the above described ablation catheters, a method may be performed of ablating lung tumor cells by sequestering a target portion of lung proximate the tumor cells, delivering hypertonic saline (HTS) to the sequestered portion of lung, and applying heat to the sequestered portion of lung. The HTS may have a sodium (NaCl) concentration of at least 3% w/v (e.g., in a range of 3% to 30% w/v, in a range of 5% to 25% w/v)
The HTS may be heated in a target region of the lung to a range of 60 to 115° Celsius. The heat may be applied by delivering radiofrequency (RF) electrical current from an RF electrode on the catheter to the HTS liquid injected into a natural airway of the lung that is near the lung tumor. The target region of lung may be exposed to heat and HTS for a duration of in a range of 30 seconds to 30 minutes (e.g., a range of 1 to 30 minutes, a range of 1 to 15 minutes, a range of 2 to 10 minutes).
The application of RF energy into the liquid effectively uses the liquid as a virtual electrode to deliver energy to ablate tumor cells. The HTS solutions conducts the RF energy to the lung tissue which causes the tissue to heat. Also, some of the RF energy heats the liquid such that the heated liquid can ablate tumor cells.
The target portion of lung is sequestered by inflating a first occluding balloon in a natural airway, wherein the balloon is proximal to the target portion of lung. Further, a second (distal) occluding balloon in the airway distal to ablation electrode may also be used to occlude the airway. The one or both balloons occlude the natural airway form a portion of the airway in which the HTS solution is injected and suppress flow of the liquid outside of that portion of the airway.
Alternatively or additionally, a fiberoptic lens may be positioned on the first elongated shaft 529 distal to the proximal occlusion structure and another lens may be positioned on the second shaft 230 distal to the distal occlusion structure, which may be used to visualize the airway distal to the selected occlusion structure(s). This may also facilitate, for example, confirmation of airway shrinking, position of the electrode(s), or injury to the airway while the occlusion structure is deployed.
Alternatively or additionally, a lung portion may be collapsed by creating a limited, controlled pneumothorax by placing a needle in the pleural space (e.g., in a pleural recess), which can facilitate collapsing the targeted lung portion. Thoracentesis (a.k.a. pleural tap) is a known procedure to remove fluid or air from around the lungs in which a needle is inserted through the chest wall into the pleural space. This may be done to alter the pressure differential between the pleural space and lung portion allowing it to collapse more easily. Optionally, a dispersive return electrode may be inserted through the pleural tap and positioned on the lung to direct RF current preferentially toward the return electrode. Optionally, a pleural tap may be used to deliver cold fluid such as physiological saline or sterile water to thermally protect areas from ablation, in particular when the tumor is at the periphery of the lung and there is a risk of ablating visceral pleura or organs such as the heart, esophagus, nerves, diaphragm or other important non-target tissues.
Optionally, any occlusion balloon may have a micropatterned surface on the exterior surface where the balloon is intended to contact an airway wall. The micropatterned surface may be molded to the balloon material and may have a hydrophilic surface that increases surface water tension creating a higher retention force that improves the ability of the occlusion balloon to remain anchored in its intended location. The improved retention may also reduce the risk of fluid leaking past the balloon. The micropattern may have a plurality of pillars having height and width dimensions less than 1000 nanometers. For example, a micropattern may be molded to the membrane using techniques known in the art (e.g., U.S. Pat. No. 8,720,047 assigned to Hoowaki, LLC)
Alternatively, as shown in
Optionally, the device 255 may be delivered over a guidewire that is left in place in lung parenchyma or a tumor following a biopsy so the needle electrode 250 can easily be placed in the same location that the biopsy was taken.
Optionally, the distal region 256 of the device 255 having a needle electrode 250 may have a spring loaded mechanism with a spring 257 and an engagement lock 258 that holds the needle electrode 250 in a first spring loaded position and when the lock 258 is released by an actuator on the proximal region of the device 255 the spring 257 pushes a shaft 259 on which the needle electrode 250 is mounted thus extending a distance 260 from a spring loaded state (e.g., 5 to 10 mm) to a deployed state (e.g., an increase of 5 to 15 mm). The momentum provided by releasing the spring-loaded mechanism may facilitate puncture of the airway wall by the needle electrode 250. The engagement lock 258 may be a mechanical mechanism such as a pivoting lever that mates with an element firmly connected to the distal shaft 259. The pivoting lever may be connected to a pull wire 261 that runs through the device shaft 229 to the proximal region of the device where it may be connected to an actuator that may be used to apply tension to the pull wire to release the lock mechanism 258.
In an alternative embodiment of a lung cancer ablation catheter capable of puncturing through an airway wall may have an RF perforation electrode on its tip (e.g., 0.5 mm diameter, 1 mm length) and the outer diameter of the shaft may taper from the RF perforation electrode diameter to the diameter of a distal ablation electrode (e.g., about 1.5 mm). An RF perforation electrode may be connectable to an energy delivery console that has an RF perforation mode. RF perforation electrodes and energy delivery profiles are known for example in the field of cardiac procedures such as septum perforation.
Optionally, the distal region of device having needle electrodes may be deflectable which may facilitate directing the sharp tip toward an airway wall in order to puncture through the wall or into a tumor and place the needle electrode 250 in lung parenchyma near or in a lung tumor or within the tumor itself.
Optionally, the proximal electrode 237 may be used to deliver ablative RF energy in addition to, instead of, or in conjunction with the distal electrode 250. The proximal electrode 237 may optionally have irrigation ports 263 in fluid communication with an irrigation lumen (not shown) that passes through the shaft 229 to the proximal region of the device 255 where the lumen is connectable to a conductive fluid source or pump. The irrigation ports 263 and 251 on the proximal electrode 237 and distal electrode 250 may be connected to the same irrigation lumen or separate lumens for delivery of conductive fluid. In embodiments having irrigation ports 263 on a proximal electrode 237 as well as irrigation ports 251 on a distal needle electrode 250 as shown in
The electrodes of the catheters may be positioned at a desired location in an airway by delivering the catheters 100 and 101 over a guide wire 104 laid down for example using an ultrathin bronchoscope. Catheters 100 and 101 may comprise a guidewire lumen 106 and 107 and be adapted for over-the-wire (OTW) exchange. Currently available devices may be used to navigate to desired positions in the patient's airway. For example, electromagnetic navigation bronchoscopy is a medical procedure utilizing electromagnetic technology designed to localize and guide endoscopic tools or catheters through the bronchial pathways of the lung. Virtual Bronchoscopy (VB) is a three-dimensional, computer-generated technique that produces endobronchial images from spiral CT data. Using a virtual, three-dimensional bronchial map from a recently computed tomography (CT) chest scan and disposable catheter set, physicians can navigate to a desired location within the lung to biopsy lesions, take samples from lymph nodes, insert markers to guide radiotherapy or guide brachytherapy catheters. Such existing technology may be used to plan for a procedure, diagnose a tumor with a biopsy, or place a guidewire for positioning one or more treatment catheters. After a guide wire 104 is placed in an airway near the target ablation zone (e.g., within 0 to 10 mm from the target ablation zone or within the target ablation zone) the ultrathin bronchoscope can be withdrawn with the wire left in place and an electrode catheter may be exchanged over the wire. Alternatively, electromagnetic navigation bronchoscopy may be used with similar results. Optionally, the multiple catheters may alternatively have a dual balloon structure, which is similar to the devices shown in
Multiple catheters with electrodes, or balloon elements, can be placed in the described fashion by exchanging a bronchoscope for catheter over the wire. After the tumor is thus surrounded by energy delivery elements and the bronchoscope and guide wire are removed, the proximal ends of catheters can be connected to the RF generator outside of the body. The technology subject of the present disclosure can also be used to ablate lymph nodes, should biopsy results indicate lymph node metastases.
Radiopaque markers on the guide wire or catheter can be used to position the electrodes at the precise desired location. For example, the RF electrodes may be radiopaque. Any of the ablation catheters disclosed herein may comprise a retention or anchoring mechanism at a distal region of the catheter to ensure its energy delivery element(s) stay in a desired position and avoid accidental dislodgement in particular when the patient breathes or coughs. For example, a retention or anchoring mechanism may comprise a section of the catheter that adopts a predefined non-linear shape (not shown), an inflatable balloon, spring loaded or wire activated splines, a stent, or deployable barbs positioned on the distal region of the catheter. Size and design of the electrode catheter can be made compatible with a working channel of regular or ultra thin bronchoscopes. Multiple electric connections for energy delivery and signal transmission (temperature and impedance) are envisioned. The ablation catheters may comprise a substance delivery lumen, which may be used to deliver substances into the airway such as drugs, contrast media to visualize the anatomy using fluoroscopy, and substances that induce lung collapse. Optionally, the guide wire lumen may function as the substance delivery lumen when the guide wire is removed, which may allow the catheter's diameter to be minimized. The ablation catheters may comprise an irrigation delivery lumen used to infuse irrigation fluid into the airway surrounding the electrodes to prevent charring and impedance rise and enable bigger lesion creation. The irrigation delivery lumen may be the same lumen as the substance delivery lumen or guide wire lumen.
As shown in
An example of bipolar or multipolar RF ablation parameters that an RF console delivers to multiple electrodes, or to multiple balloons, or to combinations of balloon and electrode energy elements, may comprise power in a range of 1 to 200 W for a duration of 30 seconds to 30 minutes. Tissue impedance may be expected to be in a range of 30 to 1000 ohms and the system may terminate or reduce power delivery if a high impedance (e.g., above 1000 ohms) is detected to avoid tissue char or uncontrolled ablation due to overheating, poor electrode contact with an airway wall. After desiccated tissue is rehydrated naturally or by irrigation, energy delivery can automatically resume. Impedance monitoring may also be used during energy delivery to determine if tissue temperature has raised sufficiently for an effective tumor ablation and instigate completion of energy delivery. The parameters may be used in a multiphasic RF ablation waveform or monophasic waveform.
Optionally, an ablation energy console may delivery ablation energy to multiple RF electrodes (e.g., on a single ablation device or on separate ablation devices) in multichannel monopolar mode and independent waveforms (e.g., VRF1, VRF2, etc. shown in
System
Devices for Endobronchial lung tumor ablation such as those disclosed herein (e.g., device 220, 255, or 270) may be part of a system 290 as shown in
Optionally, the system 290 may include more than one ablation device for example multiple ablation devices 100 and 101 deliverable through an occlusion catheter 270 as shown in
A system may include an ablation console 291, a pump 294, controller software 292, and optionally impedance and phase monitoring circuit and software 298, or any combination thereof. Furthermore, the ablation console 291, a pump 294, controller software 292, and optionally impedance and phase monitoring circuit and software 298 may be provided separately.
The software 292 may include an algorithm that controls the vacuum pump 295 to remove air from the targeted lung portion. The vacuum pump may have a pressure sensor that indicates the difference in pressure between atmosphere and the targeted lung portion. The vacuum pump may apply a maximum negative pressure difference in a range of 1 to 5 atm and the algorithm may input the pressure difference and shut off the vacuum pump when the pressure difference reaches the maximum negative pressure difference, at which time the vacuum pump may be signalled to seal air flow from the lung portion to maintain the pressure in the lung, for example by closing a valve. In embodiments wherein the conductive fluid is infused through the same lumen through which air is removed from the lung, the system may have an automatically controlled switching valve that switches fluid communication from the vacuum pump to infusion pump, for example once the algorithm detects sufficient lung portion collapse either via pressure sensor signal or tissue impedance and phase associated with the distal and proximal electrodes on the device (e.g., 220, 255, or 270). For example, the software 292 may control the ablation console 291 to deliver electrical waveforms (e.g., low power high frequency current over a range of frequency) to the distal and proximal electrode to monitor tissue impedance or phase during operation of the vacuum pump 295 and control the vacuum pump to stop when an impedance drop signifies lung collapse. The software 292 may control the pump 294 to pump conductive fluid from the fluid supply 293 to the device and into the targeted lung portion and optionally may deliver electrical waveforms to concurrently monitor impedance or phase to assess infusion. Optionally, infusion may continue (e.g., at a rate of about 5 mL/min) during delivery of ablation energy from the console 291. The software 292 may further control ablation energy delivery profiles including safety monitoring of temperature and impedance.
Alternatively, negative pressure may be manually applied to remove air from the targeted lung portion by drawing air through the catheter (e.g. through irrigation ports 235 and irrigation lumen) with a manual suction tool. The manual suction tool may be a syringe and may further have two check valves that allow air to be pulled from the catheter when the syringe is drawn and ejected to atmosphere when the syringe is depressed. A pressure sensor may be positioned in the irrigation lumen. In use, a physician may position the ablation catheter in a patient's lung, deploy the obturator, then manually apply suction to the manual suction tool while monitoring bipolar impedance measured by delivering low electrical current and measuring tissue impedance between the proximal and distal electrodes, and optionally pressure measured by the pressure sensor. A 5% to 20% drop in impedance may indicate the airway has sufficiently collapsed to proceed. Following the application of suction and identification of sufficient collapse via impedance or pressure drop a user may hold the suction tool in a static setting while monitoring impedance or pressure. A stable impedance or pressure may indicate that the targeted lung portion remains sufficiently collapsed. A rise in the impedance or pressure during this stage may indicate that the obturator is not sufficiently occluding the airway and the user may remedy by repositioning, examining, or reinflating the obturator.
If suction is applied manually a user may initiate an algorithm (e.g., by pressing an actuator on the ablatio console) when they are satisfied the targeted lung portion is sufficiently collapsed. If suction is applied automatically by an algorithm of the software 292 the algorithm may send a user message indicating the impedance or pressure drop during the suction stage is sufficient to proceed to ablation and the user may active the ablation stage (e.g., by pressing an actuator on the ablatio console) allowing the algorithm to continue.
An algorithm of the software 292 may direct the flow rate of infused conductive fluid by controlling the speed of the pump. During an ablation stage the algorithm of the software 292 may enter a priming stage that instructs the pump 294 to deliver conductive fluid from the conductive fluid source 293 without delivering ablative RF energy to prime the infusion lumen with conductive fluid and ensure at least a small amount of conductive fluid is in the airway of the targeted lung portion before ablative RF energy begins to be delivered. For example, the priming stage may include infusion of conductive fluid at a rate of 5 mL/min for 5 seconds or until measured impedance drops another 10% to 20% up to a maximum duration (e.g., 15 seconds). A drop in impedance of at least 10% may indicate that the irrigation is working properly. If impedance does not drop during this priming stage the algorithm may send a user error message indicating a possible problem with irrigation, the fluid pump, or the conductive fluid supply. If an impedance drop (e.g. of at value in a range of 10% to 20%) is measured during the priming stage the algorithm may continue to an ablation RF delivery stage.
In one embodiment, during the ablation RF delivery stage the rate of irrigation of conductive fluid may begin at 0 mL/min as ablative RF begins to be delivered. This may help to minimize the amount of conductive fluid delivered. During delivery of ablative RF, temperature, monitored by a temperature sensor 242, 442, 542, 262 associated with the ablation electrode 234, 434, 534, 250 may be input into the control algorithm and when the temperature increases to a predefined upper threshold temperature (e.g., 95° C.) irrigation flow may be turned on (e.g., at a rate of 5 mL/min) while continuing to deliver RF energy at a consistent power. The irrigation is expected cool the ablation electrode keeping it below the upper temperature threshold. If the measured temperature decreases to a predefined lower threshold (e.g., 85° C.) then irrigation flow may be instructed to stop or decrease, while maintaining constant RF power, allowing temperature to rise. The algorithm may continue to adjust flowrate to keep the temperature within the upper and lower thresholds until a preset ablation duration is reached or other termination trigger occurs. Other termination triggers may include the user manually terminating the ablation by depressing the ablation RF power actuator or an automatic shutoff error triggered by the algorithm. Automatic shutoff errors may be caused by an inability to maintain temperature within the upper and lower thresholds, failure of a component of the system (e.g., insufficient conductive fluid supply, pump malfunction, valve malfunction).
Ablation duration may be in a range of 30 seconds to 30 minutes and optionally may be chosen by a physician based on desired ablation size. For example, with animal and bench models, the authors have empirically demonstrated that using 5% HTS with an ablation electrode 234 that is 5 mm long and 1.5 mm diameter a 5 minute ablation generates a spherical ablation approximately 1.5-2 cm in diameter; at least 7 minutes results in a 2-2.5 cm diameter ablation; at least 10 minutes results in a 2.5-3 cm ablation; at least 15 minutes results in a 3 cm, or larger, diameter ablation. Depending on the size of the tumor and location relative to the target airway a physician may choose the appropriate ablation duration to encompass the tumor and input the duration to the algorithm using a user interface on the console 291. The algorithm may display on the user interface the chosen duration and estimated ablation diameter according to the input duration. Alternatively, a physician may input a desired ablation dimension (e.g., diameter) to the algorithm and the duration may be calculated and displayed. A physician may create a treatment plan depending on the size of the targeted tumor and location of the tumor. The treatment plan may include desired ablation size and placement in the airway relative to the tumor and optionally may include multiple ablations from different target positions in the lung to ablate the tumor from multiple directions if a single ablation is not estimated to completely encompass the tumor.
Optionally, following the termination of ablative RF delivery (e.g., ablation duration has completed or a premature ablation termination is triggered), suction may be activated by the algorithm to remove the conductive fluid that was infused.
Alternatively, the software 292 may control rate of delivery of conductive fluid (e.g., via pump speed) during delivery of ablation energy based on electrode temperature feedback from a temperature sensor (e.g., 242, 262) to obtain a temperature set point. For example, a constant power may be delivered and a constant infusion flow rate may be delivered and as a temperature set point is approached power, flow rate or a combination of both may be titrated to achieve the temperature set point. If actual electrode temperature is below the set point, infusion rate may be decreased and/or power may be increased. If actual electrode temperature is above the set point, infusion rate may be increased and/or power may be decreased.
Optionally, the obturator inflation pressure may be monitored by a pressure sensor 425 positioned in the obturator inflation lumen between the obturator inflator 296 or valve 297 and the obturator 231, 431, 481, 531, 581. Obturator inflation pressure may be input and monitored by the software algorithm 292 and optionally used by the algorithm for example to display the pressure on a user interface, as a requirement to begin vacuum suction (e.g., balloon inflation pressure may need to be above a predefined threshold such as 2 ATM), or as detection of a failure mode (e.g., sudden drop in balloon inflation pressure may indicate rupture of the obturator which may trigger termination of RF delivery).
A conductive fluid such as hypertonic saline may have a boiling temperature higher than 100° C., which may allow greater ablation energy to be deposited into the conductive fluid as well as a higher fluid temperature to facilitate ablation of target tissue. This may be particularly valuable when delivering thermal and electrical energy through cartilaginous airway walls to ablate a tumor, since the airway walls have a relatively low thermal and electrical conductivity and tumor ablation requires a large ablation. For example, a conductive fluid such as 20% hypertonic saline may have a boiling temperature in a range of about 105° C. to 110° C.
It may be advantageous to generate steam in an occluded target region of a lung by raising the temperature of the conductive fluid that is injected in the region close to its boiling point. Generating steam and trapping it in the target region of the lung with the occluding device (e.g., balloon) may increase the vapor pressure of the conductive fluid and, thereby, further raise its boiling point, which may allow greater ablation energy to be delivered. Exposing the airway cartilaginous wall to temperatures around 100° C. for an extended period of time, for example 2 to 10 minutes, provides the advantage of softening its consistency and of allowing conductive fluid to better infiltrate and advance towards the targeted lung tissue. Furthermore, when lung parenchyma is heated it shrinks and airways connected to the parenchyma are pulled closer together. Steam produced in a targeted lung region may pass to the associated parenchyma and shrink it prior to or during delivery of ablation energy, which may improve effectiveness of tumor ablation. An energy delivery console may comprise an energy delivery control algorithm that allows temperature set point that is within a close range about the boiling point of the conductive fluid at the pressure of the fluid in the target region. Optionally, an algorithm may have a steam-producing phase that delivers energy with a temperature set point suitable to generate steam (e.g., if 20% hypertonic saline is the conductive fluid, a temperature set point for a steam-producing phase may be in a range of 100° C. to 110° C., preferably around 105° C.). The ablation of targeted lung tissue may be performed at such increased temperature setpoint and last for a duration of 1 to 10 minutes. Alternatively, the steam-producing phase may have a predefined duration (e.g., up to 2 minutes) or be controlled by monitoring impedance between electrodes in which spikes of high impedance may indicate steam production. Yet alternatively, phases of steam production may be alternated with ablation phases of decreased temperature set points. For example, energy delivery in the first 2 minutes may be performed with a 105° C. set point, in the subsequent 2 minutes with a 85° C. set point, in the subsequent 2 minutes with a 105° C. set point and so on until the ablation duration (e.g., a total duration in a range of 8 to 15 minutes or about 10 minutes) expires or the therapeutic goal is achieved (e.g. moving average impedance increases over a targeted threshold). Optionally, a pressure sensor on the distal region of the device may be used to input a pressure signal to the controller and a rise in pressure can indicate adequate steam production. Optionally, a steam-producing phase may involve heating the conductive fluid by delivering ablation energy from the ablation elements or alternatively by delivering thermal energy from a direct heat resistive coil positioned on the device distal to the occluding device. A direct heat resistive coil may be an electrically resistive metal with an electrical insulation (e.g., polyimide, Parylene) coiled around the device shaft, which heats the conductive fluid by thermal conduction only. A steam-producing phase may be followed by a tumor ablation phase that may have a temperature set point that is lower than the set point of the steam-producing phase, as presented above.
When a conductive fluid is injected to the target region, a control algorithm may use a target set temperature in a range of 85° C. to 115° C., preferably 90° C. to 105° C., to remain below the boiling point of the conductive fluid. Alternatively, it may be desired to generate steam in the occluded target region in which case a set temperature may be in a range of 105° C. to 115° C., provided that sufficient safety mechanisms are designed into the system, such as fast RF energy shut-offs triggered by rapidly rising impedance, temperature or sudden changes in the electrical phase (i.e., the phase between the ablating current and ablating voltage).
As discussed herein, electrical impedance and phase may be measured between the proximal and distal electrodes or between either of these and a dispersive electrode (e.g., grounding pad positioned on the skin). Impedance spectroscopy may be calculated by a software algorithm in the ablation console 291 to characterize the tissue near the impedance monitoring electrode(s) through which electrical current is delivered. The tissue may be characterized to identify cancerous tissue compared to ablated cancerous tissue compared to normal tissue. Optionally or alternatively, as shown in
The system may use various means of irrigating the ablation element. Peristaltic pumps, infusion pumps, inflators/deflators may be used. Without limiting the scope of the invention, in the case of peristaltic pumps, irrigation flow rates may be controlled indirectly, by controlling the rotational speed of the pump head. The pump is calibrated so to produce a coefficient to convert its rotational speed to an irrigation volume. For example, rotational speeds in the range of 20-100 rpm may be used to generate flow rates in the range of 2-10 ml/min. In this example the conversion coefficient to convert from rotational speed to irrigation volume would be 0.1 mL/min/rpm.
Instead of flow rates, the controller may control the volume of a bolus of hypertonic solution (or of any of the other aqueous solutions discussed above). For example, a bolus of volume of 10 ml is equivalent to an irrigation rate of 2 ml/min activated for 5 min. Bolus volumes up to 60 ml may be used.
The following is a description of an embodiment of a pump control algorithm that may be part of the software 292 stored in the ablation console 291 for controlling the pump 294 for delivering conductive fluid from the conductive fluid supply 293 to the catheter 220, 255, 270 (
The Pump Control Algorithm runs every time a new Impedance or Temperature Data input is received from the ablation console. Impedance inputs may arrive at intervals of 40 milliseconds. Temperature Data inputs may arrive at intervals of 10 milliseconds. The algorithm is illustrated in the flow chart shown in
In box 610, the algorithm calculates whether the High Flow Rate and Overheat Flow Rate settings need to be adjusted.
After calculating the settings adjustments, the algorithm runs the main pump control state machine, box 611. The state machine selects one of three flow rates to be sent to the pump: Low Flow Rate, High Flow Rate, and Overheat/Over-impedance Flow Rate. Additionally, pre- and post-cool flow rates may be used for the purpose of enhancing the airway-electrode electrical contact and of cooling off the airway after ablation, respectively. However, the output of the state machine is a numeric value, in mL/min, not an enumeration. When the state machine selects a flow rate, it outputs the current setting corresponding to the flow rate. For example, if the state machine selects the Overheat/Over-impedance Flow Rate and the current setting for Overheat/Over-impedance Flow Rate is 6 mL/min, the state machine outputs 6 mL/min. For simplicity, the description herein uses identical flow rates for overheat and over-impedance conditions. Without departing from the spirit of this disclosure, different overheat and over-impedance flow rate values may be used. This will be called the state machine (SM) commanded flow rate.
If temperature or impedance exceed respective Overheat or Over-impedance thresholds, the controller may command the pump to increase flow rates to Overheat or to Over-impedance Flow Rate values. By doing so, the system attempts to prevent overheating of tissue or boiling of hypertonic saline. Once flow is increased to these higher levels, the controller may decide to maintain it to such levels for a period of time, even if the overheat or over-impedance conditions have cleared. By doing so, the controller attempts to reduce chances of recurring overheat or over-impedance conditions.
For the purpose of example, if the Calculate Settings Adjustment Section determined that the flow rate settings needed to be changed, then the commanded flow rate is adjusted to match the new settings, box 613. For example, suppose that at the start of the algorithm, High Flow Rate=2 mL/min and Overheat Flow Rate=6 mL/min. Then suppose the Calculate Settings Adjustment Section calculated pending settings of: High Flow Rate=4 mL/min and Overheat Flow Rate=8 mL/min. If the state-machine (SM) commanded flow rate is 2 mL/min (current value of High Flow Rate), then the commanded flow rate is adjusted here to 4 mL/min (new value of High Flow Rate). On the other hand, if the SM commanded flow rate is equal to the Low Flow Rate, it will not be modified here because the Low Flow Rate setting is not dynamically changed. The output of this section will be called the commanded flow rate. This is what is sent to control the pump. In general, when the temperature exceeds a T_High threshold, flow is controlled to High Flow by elements 611, 612, 613 and 614 of the state machine. Conversely, when the temperature drops below a T_Low threshold, flow is controlled to Low Flow by the same elements in
Then the pending settings changes (if any) are broadcasted to the rest of the system, box 614. The new settings will be immediately reflected in the High Flow Rate and Overheat Flow Rate spin boxes in the UI.
A more detailed view of the step of calculating pending flow settings adjustments 610 and 611 (
The overall state machine of the system is illustrated in more detail in
The NORMALCOOL state 632 is the most complex state in the state machine. Its details are shown in
A description of second system control algorithm follows, wherein a controller is used to adjust the flowrate of conductive fluid, an RF power control algorithm adjusts RF power, and the total amount of conductive fluid delivered or a condition representative of a total amount of conductive fluid delivered is monitored, for example to avoid delivering too much conductive fluid. An example plot of an ablation procedure using this control algorithm is shown in
Although delivery of conductive fluid (e.g., hypertonic saline) during delivery of RF energy is advantageous for achieving ablation of a lung tumor, too much conductive fluid delivered to the target lung region may have deleterious effects, for example too much conductive fluid may create an ablation that is larger than intended or may fill the target lung region and leak from the region, which may result in irritation or injury to non-target tissue. Thus, it is an objective of this second system control algorithm to deliver sufficient conductive fluid (e.g., hypertonic saline) to ablate a target lung tumor, while avoiding delivery of too much conductive fluid that may increase safety risks.
The procedure may involve a lung volume reduction phase, a priming phase in which conductive fluid is delivered prior to delivery of RF ablation energy to fill the fluid delivery conduit and wet the ablation electrode, an irrigated ablation phase in which conductive fluid is delivered and ablative RF energy is delivered concomitantly, and a non-irrigated ablation phase in which conductive fluid exists in the target region of the lung but is no longer added and ablative RF energy is delivered. The lung reduction phase in which suction is applied to an occluded target region of a lung containing a target tumor is may be as is described in more detail herein and may involve various occlusion elements, impedance sensors, vacuum pumps or control algorithms. Throughout the procedure, including all phases, the cumulative total volume of conductive fluid may be calculated (e.g., based on flow rates or pump speeds and times) and optionally displayed on the console's user interface. A user may reset the total calculated volume when a patient begins a procedure. A maximum total conductive fluid volume may be predefined, for example in a range of 10 mL to 20 mL. Alternatively, maximum total conductive fluid volume may be a user defined parameter set before the start of the procedure and may optionally be adjusted during the procedure, for example according to a physician's judgment, which may be based on target region volume, visual indications as seen through a bronchoscope, or patient response. Alternatively, maximum total conductive fluid volume may be calculated as a function of parameters such as desired ablation volume, target lung region volume, proximity to pleura or other tissue, proximity to the center of the tumor, patient size, and optionally be user adjustable during the procedure.
Following the lung volume reduction phase and the priming phase a user may actuate a start button to initiate the irrigated ablation phase. In this phase ablative RF power is delivered and conductive fluid is irrigated through the ablation electrode. Inputs to the control algorithm during this phase may include target ablation electrode temperature, measured ablation electrode temperature, monopolar impedance, monopolar phase, bipolar phase, and bipolar impedance. The algorithm may receive time or duration data from a timing circuit. The algorithm may output a set RF ablation power amplitude profile, an irrigation pump speed or on/off setting, and a total cumulative volume of conductive fluid (e.g., HTS). RF Power may be set to a constant amplitude, for example in a range of 50 W to 80 W (e.g., in a range of 55 W to 75 W, 55 W to 65 W, 60 W) and remain at this amplitude during the remainder of the irrigated ablation phase. Optionally, RF Power may be titrated in response to certain events, for example a quick rise in impedance caused by patient movement or desiccation of tissue adjacent the electrode, may result in a drop or pause in RF power until the impedance regains stability. Optionally, RF Power may be initially ramped from OW up to the constant amplitude for example over a period of up to 30 s (e.g., up to 25 s, up to 20 s, up to 10 s). During this phase the conductive fluid may be delivered with a bolus or flow rate determined by the control algorithm in order to adjust the measured electrode temperature to match the target set temperature. For example, the control algorithm may use a PID controller, or a variant of a PID controller, to control flow of the conductive fluid to irrigate the target region and to maintain the measured temperature at or near the target temperature. The target temperature may be in a range of 80° C. to 100° C. (e.g., in a range of 85° C. to 95° C., about 90° C.). Optionally, if the measured temperature is within a close range of the set temperature (e.g., within 4° C. of the set temperature, within 5% of the set temperature) then irrigation may be set to 0 mL/min or to a very low flow rate (e.g., less than 1 mL/min, less than 0.5 mL/min), which may further contribute to minimizing the total volume of fluid delivered. For example, if the measured temperature is above 95° C. and the set temperature is 90° C. irrigation may be turned on to lower the measured temperature and when measured temperature reaches 94° C. irrigation may be turned off. The control algorithm may continue in the irrigated ablation phase until the total cumulative delivered volume of fluid reaches, or optionally approaches, the predefined maximum volume, wherein the non-irrigated ablation phase is entered. Optionally, if the total cumulative volume is approaching the maximum volume, for example within 2 mL of the maximum volume, the RF power amplitude may be decreased, for example dropped by an amount in a range of 5 W to 20 W.
During the non-irrigated ablation phase, conductive fluid exists in the target lung region from the previous irrigated ablation phase, irrigation is stopped to avoid delivering too much fluid, and the control algorithm titrates RF power to bring measured temperature toward set temperature, for example using a PID controller or a variant of a PID controller. Set temperature may remain the same as in the previous irrigated ablation phase (e.g., 90° C.) or may be changed. Optionally, the RF power may be changed in small increments (e.g., 5 W increments).
Alternative to or in addition to comparing a measured cumulative fluid volume to a predefined maximum volume to define if the algorithm is in the irrigated ablation phase or non-irrigated ablation phase, the algorithm may use other inputs or conditions. For example, conditions that indicate the irrigated fluid may be leaking or in danger of leaking from the occluded lung space may trigger the algorithm to enter the non-irrigated phase. These triggers may also identify device failure such as a ruptured occlusion balloon. A fluid leak condition may be determined using sensors on the ablation catheter. For example, a temperature sensor proximal to the occlusion element may show an increase if hot fluid leaks and contacts the sensor. Optionally, an acceptable increase in temperature proximal to the occlusion element, for example due to thermal conduction along the catheter shaft may not trigger a change but a sudden temperature change (e.g., an increase of at least 5° C. in 1 s) may trigger a change to non-irrigated ablation, or to pause all irrigation and RF delivery until a user instructs the algorithm to continue. Impedance measured from a sensor proximal the occlusion element may indicate a leak if decreased. Bipolar impedance distal to the balloon may assess fluid volume. Pressure measured in the occluded space compared to ambient pressure or pressure proximal the occlusion element may rise as fluid is delivered and a maximum set pressure difference may trigger the algorithm to stop or pause irrigation and enter non-irrigated ablation phase. A user may input through the user interface a signal that manually interrupts the irrigated ablation phase and enters the non-irrigated ablation phase, for example if the user notices the patient coughing or sees a fluid leak via the bronchoscope.
Optionally, if a non-irrigated ablation phase is entered due to a sensed condition but the predefined total maximum volume has not been reached, the algorithm may re-enter an irrigated ablation phase if the sensed condition is relieved.
Optionally, if the total volume of fluid reaches or approaches the maximum total volume the fluid may be allowed to leak, for example by manually or automatically opening a valve, out of the occluded lung space through a lumen in the ablation catheter, optionally through a guidewire lumen. The volume of saline leaked may be measured (e.g., by weighing it or measuring with a flow meter) and subtracted from the cumulative total volume and the irrigated ablation phase may continue as long as the maximum fluid volume is not reached.
The system may use various means of irrigating the ablation element. Peristaltic pumps, infusion pumps, inflators/deflators may be used. Without limiting the scope of the invention, in the case of peristaltic pumps, irrigation flow rates may be controlled indirectly, by controlling the rotational speed of the pump head. The pump is calibrated so to produce a coefficient to convert its rotational speed to an irrigation volume. For example, rotational speeds in the range of 20-100 rpm may be used to generate flow rates in the range of 2-10 ml/min. In this example the conversion coefficient to convert from rotational speed to irrigation volume would be 0.1 mL/min/rpm.
Instead of flow rates, the controller may control the volume of a bolus of hypertonic solution (or of any of the other aqueous solutions discussed above). For example, a bolus of 10 ml is equivalent to an irrigation rate of 2 ml/min activated for 5 min. Bolus volumes up to 60 ml may be used.
Optionally, during the irrigated ablation phase, the conductive fluid may be chosen by the control algorithm from a plurality of sources having different properties, for example a hypertonic saline and a normal saline as described herein to mitigate edema.
Those of skill in the art may decide to use ramped flow rates, rather than fixed low-high flow rates. Rather than increasing the flow, for example, from a low value to a high value, a gradual increase may be employed. Similarly, various predictive algorithms may be employed to control flow rates. If the system senses a rapidly increasing temperature, the flow rate could be adjusted higher in anticipation of the temperature rise, so avoid overheating conditions. Similarly, if the system senses a rapidly dropping temperature, it could reduce the flow to lower rates, so to avoid large temperature fluctuation. Modified PID algorithms can also be used by using a nonlinear flow adjustment in response to the error value (i.e. difference between actual and set flow rates). Same control concepts may be used if the controlled parameter is a hypertonic saline bolus volume.
The Pump Control Algorithm runs every time a new Impedance or Temperature Data input is received from the ablation console. Impedance inputs may arrive at intervals of 40 milliseconds. Temperature Data inputs may arrive at intervals of 10 milliseconds. The output of the pump control algorithm is a commanded flow rate. Additionally, the algorithm may make decisions related to managing overheating or high-impedance situations. In such situations, power may be temporarily adjusted down so to bring temperature and impedance back in their normal ranges. Alternatively, the algorithm may decide to terminate delivery of energy if overheat or high-impedance conditions persist for predetermined durations of time. If it is different from the previous commanded flow rate, a new flow rate request is sent to the pump.
The system(s), catheter(s) and apparatus described above and/or claimed may use at least one controller. This controller may comprise a digital processor (CPU) with memory (or memories), an analogical type circuit, or a combination of one or more digital processing units with one or more analogical processing circuits. In the present description and in the claims, it is indicated that the controller is “configured” or “programmed” to execute certain steps. This may be achieved in practice by any means which allow configuring or programming the controller. For instance, in case of a controller comprising one or more CPUs, one or more programs are stored in an appropriate memory. The program or programs containing instructions which, when executed by the controller, cause the controller to execute the steps described and/or claimed in connection with the controller. Alternatively, if the controller is of an analog type, then the circuitry of the controller is designed to include circuitry configured, in use, to process electric signals, such as to then execute the controller steps herein disclosed and/or claimed.
While at least one exemplary embodiment of the present invention(s) is disclosed herein, it should be understood that modifications, substitutions and alternatives may be apparent to one of ordinary skill in the art and can be made without departing from the scope of this disclosure. This disclosure is intended to cover any adaptations or variations of the exemplary embodiment(s). In addition, in this disclosure, the terms “comprise” or “comprising” do not exclude other elements or steps, the terms “a” or “one” do not exclude a plural number, and the term “or” means either or both. Furthermore, characteristics or steps which have been described may also be used in combination with other characteristics or steps and in any order unless the disclosure or context suggests otherwise. This disclosure hereby incorporates by reference the complete disclosure of any patent or application from which it claims benefit or priority.
This application claims priority to U.S. provisional application 63/071,805, filed Aug. 28, 2020, the entirety of which is incorporated by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2021/046068 | 8/16/2021 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63071805 | Aug 2020 | US |
