Patent Grant
11830198
The present invention generally relates to devices and methods associated with a medical procedure, and, in one embodiment, to medical devices for use in and methods associated with the respiratory system.
Image guided surgery (IGS), also known as image guided intervention (IGI), enhances a physician's ability to locate instruments within a patient's anatomy during a medical procedure. IGS can include 2-dimensional (2D), 3-dimensional (3D), and 4-dimensional (4D) applications. The fourth dimension of IGS can include multiple parameters either individually or together such as time, motion, electrical signals, pressure, airflow, blood flow, respiration, heartbeat, and other patient measured parameters.
Existing imaging modalities can capture the movement of dynamic anatomy. Such modalities include electrocardiogram (ECG)-gated or respiratory-gated magnetic resonance imaging (MRI) devices, ECG-gated or respiratory-gated computer tomography (CT) devices, standard computed tomography (CT), 3D Fluoroscopic images (Angio-suites), and cinematography (CINE) fluoroscopy and ultrasound. Multiple image datasets can be acquired at different times, cycles of patient signals, or physical states of the patient. The dynamic imaging modalities can capture the movement of anatomy over a periodic cycle of that movement by sampling the anatomy at several instants during its characteristic movement and then creating a set of image frames or volumes.
Although significant improvements have been made in these fields, a need remains for improved medical devices and procedures for visualizing, accessing and manipulating a targeted anatomical tissue.
Among the various aspects of the present invention may be noted devices for use in and methods associated with medical procedures; such devices and methods, for example, may include devices and methods that enhance a physician's ability to locate instruments within anatomy during a medical procedure, such as image guided surgery (IGS) or image guided intervention (IGI) and such devices and methods may further include devices and methods that facilitate accessing and manipulating a targeted anatomical tissue.
Briefly, therefore, one aspect of the present invention is a method for modifying or deforming a segmented image dataset for a region of a respiratory system of a patient to the corresponding anatomy of a patient's respiratory system. The method comprises (i) forming a respiratory-gated point cloud of data that demarcates anatomical features in a region of a patient's respiratory system at one or more discrete phases within a respiration cycle of a patient, (ii) density filtering the respiratory-gated point cloud, (iii) classifying the density filtered respiratory-gated point cloud according to anatomical points of reference in a segmented image dataset for the region of the patient's respiratory system, and (iv) modifying the segmented image dataset to correspond to the classified anatomical points of reference in the density filtered respiratory-gated point cloud.
Another aspect of the present invention is a method of preparing a segmented image dataset to match the anatomy of a patient's respiratory system. The method comprises forming a respiratory-gated point cloud of data that demarcates anatomical features in a region of a patient's respiratory system at one or more discrete phases within a respiration cycle of a patient. The method further comprises density filtering the respiratory-gated point cloud, classifying the density filtered respiratory-gated point cloud according to anatomical points of reference in a segmented image dataset for the region of the patient's respiratory system, registering the classified respiratory-gated point cloud to the segmented image dataset, comparing the registered respiratory-gated point cloud to a segmented image dataset to determine the weighting of points comprised by the classified respiratory-gated point cloud, distinguishing regions of greater weighting from regions of lesser weighting and modifying the segmented image dataset to correspond to the classified respiratory-gated point cloud.
A further aspect of the present invention is a method for simulating the movement of a patient's respiratory system during respiration. The simulation method comprises (i) forming a respiratory-gated point cloud of data that demarcates anatomical features in a region of a patient's respiratory system at one or more discrete phases within a respiration cycle of a patient, (ii) density filtering the respiratory-gated point cloud, (iii) classifying the density filtered respiratory-gated point cloud according to anatomical points of reference in a segmented image dataset for the region of the patient's respiratory system, (iv) creating a cine loop comprising a plurality of modified segmented image datasets through multiple modifications of the segmented image dataset to correspond to a plurality of classified anatomical points of reference in the respiratory-gated point cloud over the respiration cycle, and (v) displaying the cine loop comprising the plurality of modified segmented image datasets over the patient's respiration cycle.
A still further aspect of the present invention is a surgical catheter for use in medical procedures. The surgical catheter comprises an elongate flexible shaft having a longitudinal axis, a proximal end portion, a distal end portion, and a handle attached to the proximal end portion. The elongate flexible shaft further comprises an outer wall extending from the proximal end portion to the distal end portion. The surgical catheter further comprises a biopsy device at the distal end portion, and an actuation wire extending from the proximal end portion to the distal end portion to operate the biopsy device. Additionally, a steering mechanism is connected to the steering actuator wherein the distal end portion may be moved relative to the proximal end portion by manipulating the steering actuator.
A still further aspect of the present invention is an apparatus comprising a steerable catheter comprising a biopsy device for accessing or manipulating tissue.
A yet further aspect of the present invention is a surgical catheter for navigated surgery, the surgical catheter comprises an elongate flexible shaft having a longitudinal axis, a proximal end portion, a distal end portion, a side exit in the distal end portion, and a handle attached to the proximal end portion. The elongate flexible shaft further comprises an outer wall extending from the proximal end portion to the distal end portion, and an electromagnetic localization element at the distal end portion. A medical instrument housed within the elongate flexible shaft that is extendable along a path from a position within the outer wall and through the side exit to an extended position outside the outer wall, the medical instrument being disposed at an angle of at least 10 degrees relative to the longitudinal axis at the side exit when in the extended position. The position of the medical instrument along the path can be calibrated to the location of the electromagnetic localization element and displayed by a surgical instrument navigation system.
A further aspect of the present invention is a method of guiding a surgical instrument to a region of interest in a patient. The method comprises displaying an image of the region of the patient, inserting a flexible lumen into the region of the patient, inserting a surgical catheter comprising an electromagnetic localization element into the lumen, navigating the surgical catheter to the region of interest, detecting a location and orientation of the electromagnetic localization element, displaying, in real-time, a virtual representation of the surgical catheter and the medical instrument superimposed on the image based upon the location and orientation of the electromagnetic localization element, and performing a medical procedure at the region of interest.
A further aspect of the present invention is a method of placing a localization element in an organ of a patient for use in a medical procedure. The method comprises attaching a first localization element to tissue in a region of the organ of a patient using an endolumenal device. The attached localization element may be separate from the endolumenal device and is registered to a segmented image dataset. The body of the patient may then be modified such that the body does not match the segmented image dataset, and the position of the first localization element is identified from outside the patient's organ using a second localization element to facilitate a medical procedure.
Other objects and features will be in part apparent and in part pointed out hereinafter.
The details of the present invention, both as to its construction and operation can best be understood with reference to the accompanying drawings, in which like numerals refer to like parts, and in which:
Referring now to
Imaging device 14 can be used to capture images or data of patient 13. Imaging device 14 can be, for example, a computed tomography (CT) device (e.g., respiratory-gated CT device, ECG-gated CT device), a magnetic resonance imaging (MRI) device (e.g., respiratory-gated MRI device, ECG-gated MRI device), an X-ray device, or any other suitable medical imaging device. In one embodiment, imaging device 14 is a computed tomography—positron emission tomography device that produces a fused computed tomography—positron emission tomography image dataset. Imaging device 14 is in communication with processor 16 and can send, transfer, copy and/or provide image data taken (captured) of patient 13 to processor 16.
Processor 16 includes a processor-readable medium storing code representing instructions to cause processor 16 to perform a process. Processor 16 may be, for example, a commercially available personal computer, or a less complex computing or processing device that is dedicated to performing one or more specific tasks. For example, processor 16 may be a terminal dedicated to providing an interactive graphical user interface (GUI). Alternatively, processor 16 may be a commercially available microprocessor, an application-specific integrated circuit (ASIC) or a combination of ASICs, which are designed to achieve one or more specific functions, or enable one or more specific devices or applications. In yet another embodiment, processor 16 may be an analog or digital circuit, or a combination of multiple circuits.
Processor 16 preferably includes a memory component (not shown) comprising one or more types of memory devices. For example, the memory component may comprise a read only memory (ROM) device and/or a random access memory (RAM) device. The memory component may also comprise other types of memory devices that may be suitable for storing data in a form retrievable by processor 16. For example, the memory component may comprise electronically programmable read only memory (EPROM), erasable electronically programmable read only memory (EEPROM), flash memory, as well as other suitable forms of memory. The memory component may also comprise a non-transitory processor-readable medium. Processor 16 may also include a variety of other components, such as for example, coprocessors, graphic processors, etc., depending upon the desired functionality of the code. Processor 16 can store data in or retrieve data from the memory component.
Processor 16 may also comprise components to communicate with devices external to processor 16 by way of an input/output (I/O) component (not shown). According to one or more embodiments of the invention, the I/O component can include a variety of suitable communication interfaces. For example, the I/O component can include wired connections, such as standard serial ports, parallel ports, universal serial bus (USB) ports, S-video ports, local area network (LAN) ports, and small computer system interface (SCSI) ports. Additionally, the I/O component may include, for example, wireless connections, such as infrared ports, optical ports, Bluetooth® wireless ports, wireless LAN ports, or the like.
In one embodiment, processor 16 is connected to a network (not shown), which may be any form of interconnecting network including an intranet, such as a local or wide area network, or an extranet, such as the World Wide Web or the Internet. The network can be physically implemented on a wireless or wired network, on leased or dedicated lines, including a virtual private network (VPN).
In one embodiment, processor 16 can receive image data from imaging device 14 and generate a segmented image dataset using various segmentation techniques, such as Hounsfield unit thresholding, convolution, connected component, or other combinatory image processing and segmentation techniques. For example, in one embodiment processor 16 can determine a distance and direction between the position of any two data points within a respiratory-gated point cloud (as described in greater detail elsewhere herein) during multiple instants in time, and store the image data, as well as the position and distance data, within the memory component. Multiple images can be produced providing a visual image at multiple instants in time through the path of motion of the patient's body.
Surgical instrument 12 may be any medical device used in a medical procedure. In one embodiment, surgical instrument 12 comprises a relatively flexible catheter that may be guided to the region or tissue of interest. Thus, for example, surgical instrument 12 may comprise or be used to implant one or more surgical devices such as a guide wire, a pointer probe, a stent, a seed, an implant, or an endoscope. It is also envisioned that the surgical instruments may encompass medical devices which are used for exploratory purposes, testing purposes or other types of medical procedures. Additionally or alternatively, surgical instrument 12 may incorporate one or more localization elements 24 that are detectable by tracking subsystem 20. As illustrated in
Imaging device 14 may be used to capture volumetric scan data (see box 32 of
Dynamic reference frame 19 may be attached to patient 13 proximate to the region (tissue) of interest within the patient 13. For ease of illustration, dynamic reference frame 19 is attached to the forehead of patient 13 in
Tracking subsystem 20 is also configured to track localization elements 24 associated with surgical instrument 12. In general, tracking subsystem 20 may comprise any tracking system typically employed in image guided surgery, including but not limited to an electromagnetic tracking system. An example of a suitable electromagnetic tracking subsystem is the AURORA electromagnetic tracking system, commercially available from Northern Digital Inc. in Waterloo, Ontario Canada. In one embodiment, tracking subsystem 20 is an electromagnetic tracking system, typically comprising an electromagnetic field generator 22 that emits a series of electromagnetic fields designed to engulf patient 13, and localization elements 24 coupled to surgical instrument 12 could be coils that would receive an induced voltage that could be monitored and translated into a coordinate position of localization elements 24. In certain embodiments, localization element 24 may be electrically coupled to twisted pair conductors to provide electromagnetic shielding of the conductors. This shielding prevents voltage induction along the conductors when exposed to the magnetic flux produced by the electromagnetic field generator. The twisted pair conductors extend from the localization element through surgical instrument 12.
Registration of image space to patient space for image guided surgery (see box 34 of
During surgery, surgical instrument 12 is directed by the physician or other healthcare professional to the region (or tissue) of interest within patient 13. Tracking subsystem 20 preferably employs electromagnetic sensing to capture position data (see box 37 of
In certain embodiments, localization element 24 comprises a six (6) degree of freedom (6DOF) electromagnetic sensor. In other embodiments, localization element 24 comprises a five (5) degree of freedom (5DOF) electromagnetic sensor. In other embodiments, localization element 24 comprises other localization devices such as radiopaque markers that are visible via fluoroscopic imaging and echogenic patterns that are visible via ultrasonic imaging. In yet other embodiments, localization elements 24 can be, for example, infrared light emitting diodes, and/or optical passive reflective markers. Localization elements 24 can also be, or be integrated with, one or more fiber optic localization (FDL) devices. In other embodiments surgical instrument 12 is non-navigated, such that it does not include any localization elements.
In operation, the field generators of localization device 22 generate magnetic fields which are detected by localization element 24. By measuring the magnetic field generated by each field generator at localization element 24, the location and orientation of localization element 24 may be computed, thereby determining position data for localization element 24 associated with surgical instrument 12. Although not limited thereto, exemplary electromagnetic tracking subsystems are further described in U.S. Pat. Nos. 5,913,820; 5,592,939; and 6,374,134 which are incorporated herein by reference in their entirety. In addition, it is envisioned that other types of position tracking devices are also within the scope of the present invention. For instance, tracking subsystem 20 may comprise a non-line-of-sight device based on sonic emissions or radio frequency emissions. In another instance, a rigid surgical instrument, such as a rigid endoscope may be tracked using a line-of-sight optical-based tracking subsystem (i.e., LED's, passive markers, reflective markers, etc.).
Position data for localization element 24, such as location and/or orientation data from the tracking subsystem 20 is in turn relayed to the processor 16. Processor 16 is adapted to receive position/orientation data (see box 37 of
As surgical instrument 12 is moved by the physician or other healthcare professional within the region of interest, its position and orientation may be tracked and reported on a real-time basis by tracking subsystem 20. Referring again to
It is envisioned that the primary of the region of interest may be supplemented by other secondary images. For instance, known image processing techniques may be employed to generate various multi-planar images of the region of interest. Alternatively, images may be generated from different view points (see box 39) as specified by a physician or other healthcare professional, including views from outside of the vessel or cavity or views that enable the user to see through the walls of the vessel using different shading or opacity. In another instance, the location data of the surgical instrument may be saved and played back in a movie format. It is envisioned that these various secondary images may be displayed simultaneously with or in place of the primary perspective image.
In addition, surgical instrument 12 may be used to generate real-time maps corresponding to an internal path traveled by the surgical instrument or an external boundary of an internal cavity. Real-time maps may be generated by continuously recording the position of the instrument's localized tip and its full extent. A real-time map may be generated by the outermost extent of the instrument's position and minimum extrapolated curvature as is known in the art. The map may be continuously updated as the instrument is moved within the patient, thereby creating a path or a volume representing the internal boundary of the cavity. It is envisioned that the map may be displayed in a wire frame form, as a shaded surface or other three-dimensional computer display modality independent from or superimposed on the volumetric perspective image of the region of interest. It is further envisioned that the map may include data collected from a localization element embedded into the surgical instrument, such as pressure data, temperature data or electro-physiological data. In this case, the map may be coded with a color or some other visual indicia to represent the collected data.
The displayed indicia 29 of surgical instrument 12 tracks the movement of surgical instrument 12 as it is moved by the physician or other healthcare professional within patient 13. In certain instances, the cardiac or respiration cycle of the patient may cause surgical instrument 12 to flutter or jitter within the patient. For instance, a surgical instrument 12 positioned in or near a chamber of the heart will move in relation to the patient's heart beat. In this instance, the indicia of the surgical instrument 12 will likewise flutter or jitter on the displayed image (see box 40 of
As shown by the flowchart of
Tracking subsystem 20 is, in turn, operable to report position data (see box 37 of
In another aspect of the present invention, surgical instrument navigation system 10 may be further adapted to display four-dimensional image data for a region of interest as shown in the flowchart of
The display of the volumetric perspective image may be synchronized (see box 66) in real-time with the cardiac or respiration cycle of patient 13 by adapting processor 16 to receive a generated timing signal (see box 46) from timing signal generator 26. As described above, the timing signal generator 26 is operable to generate and transmit a timing signal that correlates to either the cardiac cycle or the respiration cycle of patient 13. In this way, the 4D volumetric perspective image may be synchronized (see box 66) with the cardiac or respiration cycle of patient 13. The synchronized image is then displayed (see box 68) on the display 18 of the system. The four-dimensional synchronized image may be either (or both of) the primary image rendered from the point of view of the surgical instrument or the secondary image depicting the indicia of the position of surgical instrument 12 within patient 13. It is readily understood that the synchronization process is also applicable to two-dimensional image data acquire over time.
To enhance visualization and refine accuracy of the displayed image data, the surgical navigation system can use prior knowledge such as a segmented vessel or airway structure to compensate for error in the tracking subsystem or for inaccuracies caused by an anatomical shift occurring since acquisition of scan data. For instance, it is known that surgical instrument 12 being localized is located within a given vessel or airway and, therefore may be displayed within the vessel or airway. Statistical methods can be used to determine the most likely location; within the vessel or airway with respect to the reported location and then compensate so the display accurately represents surgical instrument 12 within the center of the vessel or airway. The center of the vessel or airway can be found by segmenting the vessels or airways from the three-dimensional datasets and using commonly known imaging techniques to define the centerline of the vessel or airway tree. Statistical methods may also be used to determine if surgical instrument 12 has potentially punctured the vessel or airway. This can be done by determining the reported location is too far from the centerline or the trajectory of the path traveled is greater than a certain angle (worse case 90 degrees) with respect to the vessel or airway. Reporting this type of trajectory (error) may be desired by the physicians or other healthcare professionals. The tracking along the center of the vessel or airway may also be further refined by correcting for motion of the respiratory or cardiac cycle, as described above. While navigating along the vessel or airway tree, prior knowledge about the last known location can be used to aid in determining the new location. Surgical instrument 12 or other navigated device follows a pre-defined vessel or airway tree and therefore cannot jump from one branch to the other without traveling along a path that would be allowed. The orientation of surgical instrument 12 or other navigated device can also be used to select the most likely pathway that is being traversed. The orientation information can be used to increase the probability or weight for selected location or to exclude potential pathways and therefore enhance system accuracy.
Surgical instrument navigation system 10 of the present invention may also incorporate atlas maps. It is envisioned that three-dimensional or four-dimensional atlas maps may be registered with patient specific scan data or generic anatomical models. Atlas maps may contain kinematic information (e.g., heart models) that can be synchronized with four-dimensional image data, thereby supplementing the real-time information. In addition, the kinematic information may be combined with localization information from several instruments to provide a complete four-dimensional model of organ motion. The atlas maps may also be used to localize bones or soft tissue which can assist in determining placement and location of implants.
In general, a consistent feature between lung scans is the existence of an airway tree within the lung tissue, consisting of multiple branches and carinas. The branches and carinas, however, move as a consequence of a patient's respiration. To provide more accurate navigation of an instrument through the airway tree of a patient, a set of data points may be collected from a patient pathway (e.g., an airway) and a model of points may be calculated to match the image dataset. In one embodiment, each discrete segment of the image dataset and its corresponding information are matched to the collected points, creating a “point cloud” of information. Then, the data points that create the outer region or shell of the point cloud are determined, followed by correlation or matching of the outer points to the patient's 3D image data sets.
A respiratory-gated point cloud comprises a plurality of data points corresponding to the internal volume of a patient's respiratory system measured by a localization element during the respiration cycle of a patient. Each data point of the respiratory-gated point cloud comprises three dimensional data (x, y, and z location) in reference to a 3D coordinate system. In this embodiment, each data point of the respiratory-gated point cloud may be gated to the respiration cycle of the patient. The respiratory-gated point cloud also comprises a fourth dimension representing the phase (inspiration, expiration, and, if desired, points in between) of the respiration cycle of the patient at which point the individual data point was generated. The phase information may be provided by a patient tracker that real-time tracks the patient's respiratory cycle. In certain embodiments, the generation of the individual data points in the point cloud may occur on a time-gated basis triggered by a physiological signal of the patient's respiration cycle. In other embodiments, a respiratory-gated point cloud can be collected at inspiration and another respiratory-gated point cloud collected at expiration. These two respiratory-gated point clouds can then be matched to an image dataset to assist registration. Alternatively, a single respiratory-gated point cloud can be collected including data points from both inspiration and expiration and matched to an image dataset.
Referring now to
Density filtering of the generated respiratory-gated point clouds can reduce the number of duplicate data points generated which can significantly decrease the processing time. Depending on the desired strength of filtering, a duplicate data point in the respiratory-gated point is defined as having identical three dimensional coordinates (x, y, and z) to another data point in the respiratory-gated point cloud wherein both points were generated in the same respiratory phase or a duplicate data point in the respiratory-gated point is defined as having three dimensional coordinates x1, y1, and z1 within a certain distance to another data point in the respiratory-gated point cloud having three dimensional coordinates x2, y2, and z2 wherein both points were generated in the same respiratory phase. This duplicated data point, and any additional duplicate data points can be eliminated, leaving only one data point for each three dimensional coordinate and corresponding respiratory phase. In another embodiment, additional density filtering can be done by eliminating duplicate data points without reference to a given respiratory phase. This would eliminate duplicate data points from the respiratory-gated point cloud that were generated throughout multiple phases. By eliminating the duplicate data points, a processor need not perform subsequent calculations of unnecessary data points.
Additionally, in certain embodiments, the generated point cloud may be compared to the segmented image data to determine the strength or weighting of each point collected in the point cloud. Calculating the strength or weighting of discrete points in the point cloud can enhance registration accuracy. By way of example, collecting a single string of points that are only 1 mm wide to represent an airway that is 5-6 mm wide as determined in the image model would be an insufficient point cloud. Feedback can be provided to the user such as color coding or some other visual indicia to identify the strength of the point cloud.
In one exemplary embodiment, a physician or other healthcare professional captures a respiratory-gated point cloud and the captured cloud is density filtered as previously described to form a density-filtered point cloud comprising unclassified point cloud data points. The density-filtered point cloud may then be classified using a first k-means algorithm which performs orientation classification resulting in the data points in the respiratory-gated point cloud being classified into the trachea, the right main bronchus and the left main bronchus. A second k-means algorithm is performed to further classify the data points in the respiratory-gated point cloud into control points. The respiratory-gated point cloud may then be registered to a pre-existing image dataset and the data points of the respiratory-gated point cloud are weighted. Each data point in the respiratory-gated point cloud may then be displayed to the user with a color code or some other visual indicia corresponding to the calculated weight for each data point in the respiratory-gated point cloud. In certain embodiments, feedback may be provided to the physician or other healthcare professional indicating that additional respiratory-gated point cloud data points may be collected in locations having lesser weighting. This method may then be repeated until a desired weighting is achieved across the respiratory-gated point cloud.
Image datasets may not perfectly match if the image data was acquired at a different phase in the respiration cycle (e.g., full inspiration, partial inspiration, full expiration, etc.) or if the patient's anatomy has been changed due to positioning on the table, weight gain/loss, skin shift, delivery of drugs, etc. In such embodiments, an image dataset taken at a first time point can be modified or deformed to better correspond to the respiratory-gated point cloud generated during the medical procedure (i.e., a second and subsequent time point). Additionally, a sequence of motion of the respiratory-gated point cloud can be generated over the complete procedure or significant period of time. The distance, range, acceleration, and speed between one or more selected pairs of respiratory-gated data points within the point cloud generated by the localization element 624 (see
Referring now to
A deformation vector field can be calculated between a first set of points in the respiratory-gated point cloud that correspond to inspiration and a second set of points in the respiratory-gated point cloud that correspond to expiration. This deformation vector field may then be used to modify or deform a pre-existing or pre-acquired segmented image dataset, taken from a first time interval, to correspond to the correlated anatomical points of reference in the respiratory-gated point cloud, taken during a second time interval. In certain embodiments, the segmented image dataset to be modified is from a first discrete phase of the patient's respiration cycle and the respiratory-gated point cloud is from a second and different discrete phase of the patient's respiration cycle. Accordingly, a pre-existing or pre-acquired segmented image dataset can be from an inspiration phase and it can be modified or deformed to the expiration phase using the deformation vector field calculated from the respiratory-gated point cloud. Thus a segmented image dataset need not require an image for each phase of the patient's respiration cycle.
A deformation vector field can be calculated between data points in the respiratory-gated point cloud that correspond to different phases of the patient's respiratory cycle. The image dataset from a first time interval may then be modified or deformed by the deformation vector field to match the anatomy of the patient during the second time interval. This modification or deformation process can be done continuously during the medical procedure, producing simulated real-time, intra-procedural images illustrating the orientation and shape of the targeted anatomy as a catheter, sheath, needle, forceps, guidewire, fiducial delivery devices, therapy device (ablation modeling, drug diffusion modeling, etc.), or similar structure(s) is/are navigated to the targeted anatomy. Thus, during the medical procedure, the physician or other healthcare professional can view selected modified or deformed image(s) of the targeted anatomy that correspond to and simulate real-time movement of the anatomy. In addition, during a medical procedure being performed during the second time interval, such as navigating a catheter or other instrument or component thereof to a targeted anatomy, the location(s) of a localization element (e.g., an electromagnetic coil sensor) coupled to the catheter during the second time interval can be superimposed on an image of a catheter. The superimposed image(s) of the catheter can then be superimposed on the modified or deformed image(s) from the first time interval, providing simulated real-time images of the catheter location relative to the targeted anatomy. This process and other related methods are described in U.S. Pat. No. 7,398,116, the entire disclosure of which is incorporated herein by reference.
The deformation vector field may be calculated between a first set of points in the respiratory-gated point cloud that correspond to a first respiration phase and a second set of points in the respiratory-gated point cloud that correspond to a second respiration phase. Typically, the first respiration phase is inspiration and the second respiration phase is expiration. Additionally, the two phases can be reversed wherein the first phase is expiration and the second phase is inspiration. For example, the deformation vector field can be applied to modify or deform an image dataset of 3D fluoroscopic images or CT images in order to compensate for different patient orientations, patient position, respiration, deformation induced by the catheter or other instrument, and/or other changes or perturbations that occur due to therapy delivery or resection or ablation of tissue.
In some embodiments, for example, real-time respiration compensation can be determined by applying an inspiration-to-expiration deformation vector field. In combination with the respiratory signal, for example, the surgical instrument location can be calculated using the deformation vector field. A real-time surgical instrument tip correction vector can be applied to a 3D localized instrument tip. The real-time correction vector is computed by scaling an inspiration-to-expiration deformation vector (found from the inspiration-to-expiration deformation vector field) based on the respiratory-gated point cloud. This correction vector can then be applied to the 3D localized surgical instrument tip. This can further optimize accuracy during navigation.
An example of an algorithm for real-time respiration compensation can be found in :
Although
Deformation of 2D images can also be calculated based upon therapeutic change of tissue, changes in Hounsfield units for images, patient motion compensation during the imaging sequence, therapy monitoring, and temperature monitoring with fluoroscopic imaging, among other things. One potential issue with conventional therapy delivery, for instance, is monitoring the therapy for temperature or tissue changes. In accordance with the methods described herein, this monitoring can be carried out using intermittent fluoroscopic imaging, where the images are compensated between acquisition times to show very small changes in image density, which can represent temperature changes or tissue changes as a result of the therapy and/or navigation.
Another method to modify/deform the image dataset and match to the patient is to segment the airway from the image dataset and skeletonize it to find the central airway tree. The physician or other healthcare professional can then modify/deform the image dataset by identifying points within the image space and patient space that match such as the main carina and/or collect multiple branch information that defines branches and carina points between branches. These points can be used to modify or deform the image dataset. Deformation of a complete 3D volume would be time consuming so methods to create deformation matrices for regions may be preferred.
In general, the embodiments described herein have applicability in “Inspiration to Expiration”-type CT scan fusion. According to various methods, the user navigates on the expiration CT scan to aid accuracy, while using the inspiration scan to aid airway segmentation. In one embodiment, for example, a user could complete planning and pathway segmentation on an inspiration scan of the patient. Preferably, a deformation vector field is created between at least two datasets. The deformation vector field may then be applied to the segmented vessels and/or airways and the user's planned path and target. In these and other embodiments, the deformation vector field can also be applied to multiple datasets or in a progressive way to create a moving underlying dataset that matches the patient's respiratory or cardiac motion. In other embodiments, using a respiratory-gated point cloud, a deformation vector field is calculated between a first set of points in the respiratory-gated point cloud that correspond to inspiration and a second set of points in the respiratory-gated point cloud that correspond to expiration. This deformation vector field may then used to modify or deform a pre-existing or pre-acquired segmented image dataset to correspond to the correlated anatomical points of reference in the respiratory-gated point cloud.
In accordance with various embodiments, “Inspiration to Expiration” CT fusion using the lung lobe centroid and vector change to modify an airway model may be used to translate and scale each airway based on the lung lobe change between scans. The lung is constructed of multiple lobes and these lobes are commonly analyzed for volume, shape, and translation change. Each lobe changes in a very different way during the patient's respiration cycle. Using this information to scale and translate the airways that are located in each lobe, it is possible to adapt for airway movement. This scaled airway model can then be linked to the 4D tracking of the patient as described herein. In accordance with various embodiments using a respiratory-gated point cloud, this technique may be used to translate and scale each airway based on the lung lobe change between respiration phases. The lung is constructed of multiple lobes and these lobes are commonly analyzed for volume, shape, and translation change. Each lobe changes in a very different way during the patient's respiration cycle. Using the respiratory-gated point cloud information to scale and translate the airways that are located in each lobe, it is possible to adapt for airway movement. This scaled airway model can then be linked to the 4D tracking of the patient as described herein.
In general, it may also be preferable to reduce the level of radiation that patients are exposed to before or during a procedure (or pre-procedural analysis) as described herein. One method of reducing radiation during the acquisition of a 3D fluoroscopic dataset (or other dataset described herein), for example, is to use a deformation vector field between data points in a respiratory-gated point cloud to reduce the actual number of 2D images that need to be acquired to create the 3D dataset. In one particular embodiment, the deformation field is used to calculate the deformation between images in the acquisition sequence to produce 2D images between the acquired slices, and these new slices can be used to calculate the 3D fluoroscopic dataset. For example, if 180 2D image slices were previously required, e.g., an image(s) taken every 2 degrees of a 360 degree acquisition sequence, in accordance with some embodiments 90 2D images can be acquired over a 360 degree acquisition sequence and the data from the images that would have ordinarily been acquired between each slice can be calculated and imported into the 3D reconstruction algorithm. Thus, the radiation is effectively reduced by 50%.
In another embodiment, illustrated by
In addition to modifying or deforming the segmented image dataset, in one embodiment of the present invention the movement of a patient's respiratory system in the patient's respiration cycle over the patient's entire respiration cycle may be simulated in a method comprising (i) forming (see box 700 of
In another aspect, the system involves generating a respiratory-gated point cloud of a dynamic anatomy using implanted localization elements. In general, one or more (and typically multiple, e.g., 2, 3, 4, or more) localization elements may be placed in the organ and tracked continuously and registered to a discrete section of the organ. In this embodiment, the localization elements may have a pigtail or anchoring mechanism that allows it to be attached to an internal organ or along a vessel. Using image processing techniques, voxels from an image dataset, or set of voxels from an image dataset; multiple 3D data sets of the organ can be used to create discrete sections of the organ (i.e., in a grid-like pattern). For each section, a deformation vector field analysis can be performed between the phases of the organ and/or based upon the motion of the organ tracked by localization elements attached to or adjacent to a wall of the organ such that the motion of the organ is translated to the sensors. Each section will then have unique signature or deformation vector field, which can be matched to the tracked motion of the localization element(s) attached to the organ. For example, the wall localization element motion will match the space-time signature of the device. Preferably, a deformation vector field is created between at least two datasets. The deformation vector field may then be applied to the segmented vessels and/or airways and the user's planned path and target.
Another technique for maximizing registration accuracy is a centroid finding algorithm that can be used for refining point locations in a local area. Often, a user will want to select a vessel bifurcation. The vessel bifurcation will be seen as a bright white location on the CT and US images. An algorithm can be used to help the user select the center location for these locations. Once a user selects a point on the image, the local algorithm can be employed to find similar white voxels that are connected and, for that shape in the 3D space, refine the point to the centroid or any other point (such as, for example, the most anterior or most posterior point).
Skeletonization of the segmented image dataset can help refine the respiratory-gated point cloud. It may be difficult to capture a respiratory-gated point cloud that would match a patient image dataset due to the inability to physically touch the airway wall in many orientations. Therefore the system can use the calculated centerlines between the dataset and the respiratory-gated point cloud to refine accuracy. Various methods of skeletonization are well known in the art and can be applied to the image datasets of certain embodiments of the present invention.
In an alternative embodiment, registering the classified respiratory-gated point cloud to the segmented image dataset comprises registering the classified respiratory-gated point cloud representing at least one branch of the patient's respiratory system to corresponding anatomical points of reference in the registered segmented image data set representing the branch(es) of the patient's respiratory system. In certain embodiments, the classified respiratory-gated point cloud sections corresponding to the trachea, the right main bronchus (RMB), and the left main bronchus (LMB) are registered to a plurality of branches of the patient's respiratory system, wherein the plurality of branches comprise the trachea, the right main bronchus (RMB), and the left main bronchus (LMB). Rotational shifts may be found through lumen data collection. Matching the trachea, RMB, and LMB in patient space and image space will provide rotational registration refinement. While the lung is commonly defined as one organ, in certain embodiments separate registrations between the right and left lung or even different lobes of the lung can provide additional refinement. Carina touch points can be used to perform translational shifts to the registration between patient space and image space.
In one embodiment a lung atlas can be used to develop patient specific airway trees, lung regions, lobes, lymph nodes, vessels, and other structures. These structures can be key to things such as correctly staging lung cancer. Correctly identifying the spread of cancer to lymph nodes can determine the best course of patient treatment. Recording the sampled locations to determine a consistent staging methodology and correctly identifying the region of the lung is key. A lung atlas can also be used to automatically select registration points within a patient such as the Main Carina or other branch points that can be touched by the user to register a dataset to the patient space. Using a lung atlas with an airway tree segmented, a patient specific airway tree can be determined by deforming the lung atlas to the patient's dataset to produce a patient specific airway tree. This can be used for a navigation pathway map, initialization points for other image processing steps, or to produce an error metric for multiple algorithms. Accordingly, in certain embodiments, a lung atlas can be modified or deformed according to the respiratory-gated point cloud.
In another embodiment, 3D image datasets of an organ (e.g., the heart or lung(s)) are segmented to determine a center line of the pathway, such that a string of points, shape or diameter of the pathway can be determined. Patient image information can be matched to the localization information in order to match 3D image space to actual patient space. Thus, an airway shape may be provided along with discrete segments providing shape, orientation, and location information.
In yet another embodiment, 3D image datasets of an organ (e.g., the heart or lung(s)) are segmented to determine a wall, inner surface, or effective inner surface of the pathway, such that a shape or diameter of the pathway can be determined. An effective inner surface may be the representation of an airway that can be tracked based upon the instrumentation used to collect points. An instrument dragged through or passed through and airway may be limited to its ability to track exactly along the surface of the airway and is generally a fixed distance from the wall (i.e., a 5 mm diameter airway may only be tracked in a 3 mm diameter space as there is a 1 mm offset of the sensor from the instrument or device it is inserted to the outer wall). Patient image information may be matched to the localization information in order to match 3D image space to actual patient space. Thus, an airway shape is provided along with discrete segments providing shape, orientation, and location information.
In one embodiment, the tracking of therapy delivery such as energy, material, device, or drug is described. Delivery of a therapy for COPD, asthma, lung cancer and other lung diseases needs tracking of the delivery location and/or pattern. This can be done over treatment sessions (i.e., Bronchial Thermoplasty) or have a dynamically changing dose or energy (RF, cryo, microwave, steam, radiation, or drugs) based on location and trajectory of the delivery device. Using the tracking location and trajectory to modify the dose or energy real-time is described. The power of an ablation device can be changed as the device is directed at the target or can be turned off if outside a defined region. For delivery of therapy that is delivered over multiple sessions, the recorded locations of treated areas can be merged together for each session to give the patient a complete treatment. The treatments can also be modeled before delivery to determine a more effective delivery pattern, dose, or energy.
In another embodiment, a catheter used in the forming of the respiratory-gated point cloud can be integrated with one or more fiber optic localization (FDL) devices and/or techniques. In this way, the localization element (such as an electromagnetic (EM) sensor) provides the 3D spatial orientation of the device, while the FDL provides shape sensing of the airway, vessel, pathway, organ, environment and surroundings. Conventional FDL techniques can be employed. In various embodiments, for example, the FDL device can be used to create localization information for the complete pathway or to refine the localization accuracy in a particular segment of the pathway. By either using 3D localization information, shape, or both detected by the FDL device, the system can use a weighted algorithm between multiple localization devices to determine the location and orientation of the instrument in the patient. The FDL device can also be used as or in conjunction with the PTD to track the patient's motion such as respiration or heartbeat.
In other embodiments, surgical instrument 12 (see
Still other embodiments involve using video input of the bronchoscope to adjust the virtual “fly-through” view to be consistent with the user's normal perspective. For example, conventional video processing and matching techniques can be used to align the real-time video and the virtual image.
Still other embodiments involve using bronchoscopic video to provide angular information at a current location to provide targeting or directional cues to the user. Angular information can be derived from the location of patient anatomy in the image and the relative size of each within the image. Using information extracted from the video captured by the bronchoscope, the system can determine the direction of the display. This can be done using, for example, translation, rotation, or a combination of both. By comparing the real-time image captured to the modified image constructed from the respiratory-gated point cloud, the system can use this information to align the modified image and/or enhance the system accuracy.
In yet another embodiment, a high-speed three-dimensional imaging device, such as an optical coherence tomography (OCT) device, can be tracked. In accordance with conventional methods, such a device can only view 1-2 mm below the surface. With a localization element (e.g., electromagnetic sensor) attached in accordance with the systems and methods described herein, multiple 3D volumes of data can be collected and a larger 3D volume of collected data can be constructed. Knowing the 3D location and orientation of the multiple 3D volumes will allow the user to view a more robust image of, for example, pre-cancerous changes in the esophagus or colon. This data can also be correlated to pre-acquired or intra-procedurally acquired CT, fluoroscopic, ultrasound, or 3D fluoroscopic images to provide additional information.
Among several potential enhancements that could be provided by a surgical instrument navigation system as described herein is that a user could overlay the planned pathway information on to the actual/real-time video image of the scope or imaging device (such as ultrasound based device). Additionally, the system and apparatus could provide a visual cue on the real-time video image showing the correct direction or pathway to take.
According to another particular embodiment, 3D location information may be used to extend the segmented airway model. The 3D airway can be extended as the instrument is passed along the airway by using this location information as an additional parameter to segment the airway from the CT data. Using an iterative segmentation process, for instance, the 3D location information of the instrument can be used to provide seed points, manual extension, or an additional variable of likelihood of a segmented vessel or airway existing in the 3D image volume. These added airways can be displayed in a different format or color (for example) or some other visual indicia to indicate to the user that they are extending the segmented airway using instrument location information.
The multi-dimensional imaging modalities described herein may also be coupled with digitally reconstructed radiography (DRR) techniques. In accordance with a fluoroscopic image acquisition, for example, radiation passes through a physical media to create a projection image on a radiation-sensitive film or an electronic image intensifier. Given a 3D or 4D dataset as described herein, for example, a simulated image can be generated in conjunction with DRR methodologies. DRR is generally known in the art, and is described, for example, by Lemieux et al. (Med. Phys. 21(11), November 1994, pp. 1749-60).
When a DRR image is created, a fluoroscopic image is formed by computationally projecting volume elements, or voxels, of the 3D or 4D dataset onto one or more selected image planes. Using a 3D or 4D dataset of a given patient as described herein, for example, it is possible to generate a DRR image that is similar in appearance to a corresponding patient image. This similarity can be due, at least in part, to similar intrinsic imaging parameters (e.g., projective transformations, distortion corrections, etc.) and extrinsic imaging parameters (e.g., orientation, view direction, etc.). The intrinsic imaging parameters can be derived, for instance, from the calibration of the equipment.
Referring now to
According to another embodiment of the present invention,
In another embodiment, an alternative method of generating a 4D dataset for 4D thoracic registration using surgical instrument navigation system 10 is illustrated by
Other embodiments include, for example, using an electromagnetic sensor as an LC or energy transmission device. This stored energy could be used to actuate a sampling device such as forceps or power a diagnostic sensor.
In various aspects and embodiments described herein, one can use the knowledge of the path traveled by the surgical instrument and segmented airway or vessel from the acquired image (e.g., CT) to limit the possibilities of where the surgical instrument is located in the patient. The techniques described herein, therefore, can be valuable to improve virtual displays for users. Fly through, fly-above, or image displays related to segmented paths are commonly dependent upon relative closeness to the segmented path. For a breathing patient, for example, or a patient with a moving vessel related to heartbeat, the path traveled information can be used to determine where in the 4D patient motion cycle the system is located within the patient. By comparing the 3D location, the patient's tracked or physiological signal is used to determine 4D patient motion cycle, and with the instrument's traveled path, one can determine the optical location relative to a segmented airway or vessel and use this information to provide the virtual display.
The surgical instrument navigation system of certain embodiments of the present invention may also incorporate atlas maps. It is envisioned that three-dimensional or four-dimensional atlas maps may be registered with patient specific scan data, respiratory-gated point clouds, or generic anatomical models. Atlas maps may contain kinematic information (e.g., heart and lung models) that can be synchronized with four-dimensional image data, thereby supplementing the real-time information. In addition, the kinematic information may be combined with localization information from several instruments to provide a complete four-dimensional model of organ motion. The atlas maps may also be used to localize bones or soft tissue which can assist in determining placement and location of implants.
As noted herein, a variety of instruments and devices can be used in conjunction with the systems and methods described herein.
As a result of or in the course of certain surgical procedures, a patient's physical state may be changed relative to an acquired image dataset. Incisions, insufflations, and deflation of the lung and re-positioning of the patient are just some of the procedures that may cause a change in the patient's physical state. Such changes in physical state may make it more difficult to find a lesion or point in an organ of the patient. For example, in a lung wedge resection the thoracic surgeon is palpating the lung to find the lesion to resect; if this lesion is 1-2 cm under the surface it can be very difficult to find.
In one embodiment, a first localization element is placed at a location or region of interest (e.g., a tumor) within an organ of a patient and a second localization element is used to identify the location of the first localization element from outside the organ in which the first localization element has been positioned. Preferably, the first localization element is attached or otherwise connected to tissue or situated such that its position relative to the location or region of interest remains fixed. In some embodiments, for example, the first localization element can be sutured in place, and/or or may have barbs, hooks, flexed spring shape (bowed) and/or wires, or other suitable connection techniques, to hold it substantially in place.
Referring now to
In one embodiment, first localization element 904 is positioned in the organ and may be registered to a segmented image dataset prior to any procedural resection or incision has occurred. Otherwise, pre-procedural images may not match the patient's anatomy (e.g., once an incision is made, the patient is insufflated for a VATS procedure, or the patient is otherwise re-positioned).
After the first localization element 904 is positioned in an organ and registered, as shown in
Although the second localization element 908 will be outside the organ into which first localization element 904 is placed, it need not be outside the body of the patient. In certain embodiments of the present invention, second localization element 908 can be inserted into the patient through a surgical portal. In other embodiments, second localization element 908 will be outside the body of the patient. Optionally, and as illustrated in
As illustrated in
In certain embodiments, the first, second and (optional) third localization elements may all be elements of a tracking subsystem 20 (see
In one embodiment of the present invention, surgical instrument 12 (see
In accordance with one embodiment of the present invention and referring now to
In certain embodiments, elongate flexible shaft comprises a flexible shaft portion 202 at its proximal end portion 232 and a steerable shaft portion 203 at its distal end portion 234. In other embodiments, elongate flexible shaft 230 comprises flexible shaft portion 202 at its distal end portion 234 and a steerable shaft portion at its proximal end portion 232. Flexible shaft portion 202 has a first stiffness and steerable shaft portion 203 has a second stiffness that is less than the first stiffness. Stated differently, flexible shaft portion 202 may be comprised of a more rigid material which has a first stiffness, while steerable shaft portion 203 may be comprised of a softer material having a second stiffness. In certain embodiments, flexible shaft portion 202 is formed from a relatively high-durometer material and steerable shaft portion 203 is formed from a less stiff, lower-durometer material than the flexible shaft portion. Additionally, flexible shaft portion 202 may be reinforced with a molded-in braided reinforcement material. In one alternative embodiment, flexible shaft portion 202 comprises a spring having a first coil diameter and steerable shaft portion 203 comprises a spring having a second coil diameter. The first coil diameter may be greater than the second coil diameter and, accordingly, the first coil diameter of the flexible shaft portion has a greater stiffness than the second coil diameter of the steerable shaft portion. In one embodiment, elongate flexible shaft 230, including flexible shaft portion 202 and steerable shaft portion 203, are preferably formed from a biocompatible material such as Pebax™, manufactured by Arkema.
Biopsy device 220 is at distal end portion 234 of elongate flexible shaft 230 and, in certain embodiments, may be used to access or manipulate tissue. In one embodiment, biopsy device 220 is operated by actuation wire 212 (see
Referring again to
Referring now to
As illustrated in
In another embodiment, elongate flexible shaft 230 of steerable catheter 200 houses more than one pull wire 210 attached to steering actuator 218. The use of multiple pull wires may be preferred in some embodiments over steerable catheters having a single pull wire. A steerable catheter having only one pull wire 210 attached to steering actuator 218 will typically bend in only one direction, commonly referred to as uni-directional steering. A steerable catheter capable of only uni-directional steering could be rotated, such that any point surrounding the distal end of the elongate flexible shaft may be reached by bending the catheter tip and rotating the catheter. Two or more pull wires (e.g., two, three, four, or even more) attached to steering actuator 218, however, could provide multi-directional steering thereby permitting the elongate flexible shaft to be deflected in two or more directions.
In one embodiment, elongate flexible shaft 230 comprises one or more lumens extending from proximal end portion 232 to distal end portion 234 of elongate flexible shaft 234 that may be used to deliver a medical device or therapy to a surgical site (e.g., fluids, biopsy devices, drugs, radioactive seeds, combinations thereof, or the like). In other embodiments, the lumen(s) may house additional structures such as electrical wires or optical fibers connected to biopsy device 220 on distal end portion 234 of elongate flexible shaft 230. In other embodiments, a vacuum pressure may be applied to the lumen(s) to assist removal of tissue or fluid. In certain embodiments, the lumen may be a working channel in which a biopsy device such as an aspiration needle is housed and operated, wherein the aspiration needle is described in greater detail elsewhere herein (see
Referring now to
In one embodiment, as illustrated in
Referring now to
Typically, the outer diameter of elongate flexible shaft 230 of steerable catheter 200 is less than 5 mm. By way of example, in certain embodiments, the outer diameter of elongate flexible shaft 230 of steerable catheter 200 is less than 1 mm. By way of further example, in certain embodiments, the outer diameter of elongate flexible shaft 230 of steerable catheter 200 is less than 2 mm. By way of further example, in certain embodiments, the outer diameter of elongate flexible shaft 230 of steerable catheter 200 is less than 3 mm. By way of further example, in certain embodiments, the outer diameter of elongate flexible shaft 230 of steerable catheter 200 is less than 4 mm. By way of further example, in certain embodiments, the outer diameter of elongate flexible shaft 230 of steerable catheter 200 is less than 5 mm.
While in certain embodiments the steerable catheter 200 is non-navigated, other embodiments of the steerable catheter 200 are navigated. In certain embodiments in which steerable catheter 200 is navigated, a localization element 24 is positioned in elongate flexible shaft 230 or biopsy device 220, preferably at or near the distal end thereof. In certain embodiments, localization element 24 may comprise electromagnetic sensors. However, in other embodiments the steerable catheter 200 may be navigated wherein elongate flexible shaft 230 or biopsy device 220 may further comprise radiopaque markers visible via fluoroscopic imaging, or echogenic materials or patterns that increase visibility of the tip component under an ultrasonic beam. In yet other embodiments the steerable catheter 200 may be navigated wherein distal end portion 234 of elongate flexible shaft 230 or distal end of biopsy device 220 may further comprise radiopaque markers visible via fluoroscopic imaging, or echogenic materials or patterns that increase visibility of the tip component under an ultrasonic beam. In one embodiment, localization element 24 comprises a six (6) degree of freedom (6DOF) electromagnetic sensor. In another embodiment the localization element comprises a five (5) degree of freedom (5DOF) electromagnetic sensor. Using the localization element, the user can have the location of the biopsy device 220 is defined on the navigation screen.
In one embodiment, localization element 24 may be attached to actuation wire 212. Movement of actuation wire 212 as handle 216 is manipulated causes coordinated movement of localization element 24 thereby providing an indication that biopsy device 220 is being operated. In accordance with other embodiments, for example, a localization element as described herein (e.g., an electromagnetic (EM) sensor) is affixed (preferably permanently affixed, but may also be removable) to a biopsy device or medical instrument so that both the biopsy device or medical instrument (or component thereof) and the localization element move together, such that they can be imaged and viewed. In one embodiment, for example, biopsy device 220 is an aspiration needle and the needle tip and the sensor move together. In another embodiment, for example, biopsy device 220 is a brush, forceps, or forceps tissue capture mechanism and these components and the localization element move together. In these and other embodiments, handle 216 may be coupled with localization element 24, thus allowing movement tracking. These various embodiments allow the biopsy device or medical instrument (and components thereof) to be tracked using the localization element, improving overall accuracy and reliability.
Referring now to
Referring now to
Referring now to
Referring now to
Referring now to
In certain embodiments, as discussed herein, localization element 24 may be positioned at or near the distal end of biopsy device 220. Alternatively, in other embodiments, localization element 24 is positioned at or near the proximal end of biopsy device 220. In yet other embodiments, multiple localization elements 24 (e.g., 5DOF or 6DOF electromagnetic sensors) and/or radiopaque markers, echogenic patterns, etc. may be positioned at or near the proximal end of biopsy device 220. Alternatively, in other embodiments, multiple localization elements 24 (e.g., 5DOF or 6DOF electromagnetic sensors) and/or radiopaque markers, echogenic patterns, etc. may be positioned at or near the distal end of the biopsy device 220. In yet other embodiments, multiple localization elements 24 (e.g., 5DOF or 6DOF electromagnetic sensors) and/or radiopaque markers, echogenic patterns, etc. may be positioned at or near the proximal and distal ends of the biopsy device 220. In another embodiment of the present invention, biopsy device 220 contains no localization element 24. Alternatively, localization element 24 is positioned at or near distal end portion 234 of elongate flexible shaft 230. By positioning localization element 24 at or near distal end portion 234 of elongate flexible shaft 230, in certain embodiments, the biopsy device 220 could be made smaller or at a lesser cost. In this embodiment, biopsy device 220 may comprise any of the biopsy devices described elsewhere herein (see, e.g.,
In yet other embodiments, forceps device 300 (see
Referring now to
Referring now to
As shown in
In yet other embodiments, auger device 400 may be visible via fluoroscopic imaging wherein an angled or directionally arranged radiopaque marker pattern 115 is at or near the proximal end and/or the distal end of auger device 400 (see
Referring now to
In another embodiment, as illustrated by
In yet other embodiments, boring bit device 500 may be visible via fluoroscopic imaging wherein an angled or directionally arranged radiopaque marker pattern 115 is at or near the proximal end and/or the distal end of boring bit device 500 (see
Referring now to
In yet other embodiments, aspiration needle device 1100 may be visible via fluoroscopic imaging wherein an angled or directionally arranged radiopaque marker pattern 115 is at or near the proximal end and/or the distal end of aspiration needle device 1100 (see
Referring now to
In yet other embodiments, brush device 1000 may be visible via fluoroscopic imaging wherein an angled or directionally arranged radiopaque marker pattern 115 is at or near the proximal end and/or the distal end of brush device 1000 (see
In another embodiment of a brush device, as brush is pushed out of the brush housing the brush is squeezed through a smaller opening to collect the sampled tissue that was trapped when extended. When fully extended, the brush device end would be open so that the brush can be retracted and the sampled tissue can be pulled into the instrument. The brush device would then close as the brush is extended out and the sampled tissue could be scraped/squeezed from the brush bristles and collected in a reservoir. In certain embodiments, a vacuum pressure may be added to this device in conjunction or in lieu of the scrapping process to clean the brush.
In yet another embodiment, biopsy device 220 is extendable is extendable along a path from a position within the outer wall 236 through a side exit to a position outside the outer wall 236 at an angle of at least 30 degrees relative to the longitudinal axis, wherein the path of biopsy device 220 can be calibrated to the location of an electromagnetic localization sensor positioned at the distal end portion of the elongate flexible shaft and displayed by a surgical instrument navigation system. Various embodiments of biopsy devices exiting from the side of the elongate catheter body can be seen in
In these and other embodiments, a portion of biopsy device 220 may be bent at an angle relative longitudinal axis 207. A bend in biopsy device 220, may allow the physician or other healthcare professional to rotate biopsy device 220 and sample the region (or tissue) of interest via several different pathways or positions. This may also increase the amount of region (or tissue) of interest that may be sampled in a single pass, and may improve targeting of regions (or tissue) of interest to be sampled. Moreover, a bend in biopsy device 220 may assist in targeting a region that is not necessarily directly in a patient pathway (e.g., an airway), but may be next to the pathway, thus enabling the physician or other healthcare professional to direct biopsy device 220 to a desired location off the axis of the airway.
The method or procedure of guiding the steerable catheter 200 of certain embodiments to a desired target tissue in the respiratory system of a patient comprises: (i) inserting a flexible lumen into the patient, (ii) inserting into the flexible lumen steerable catheter 200, (ii) navigating steerable catheter 200 through the respiratory system of the patient, (iii) manipulating steering actuator 218 to cause a deflection in longitudinal axis 207, and (iv) performing a medical procedure at the region (or tissue) of interest. In embodiments where steerable catheter 200 is a navigated catheter, the method or procedure of guiding the steerable catheter 200 of certain embodiments to a desired target tissue of a patient includes the additional steps of: (i) displaying an image of the region of the patient, (ii) detecting a location and orientation of localization element 24, and (iii) displaying, in real-time, biopsy device 220 on the image by superimposing a virtual representation of steerable catheter 200 and biopsy device 220 on the image based upon the location and orientation of localization element.
A method or procedure of guiding steerable catheter 200 of certain embodiments to a desired target tissue in the respiratory system of a patient may comprise inserting a flexible lumen into the patient, and inserting into the flexible lumen steerable catheter 200. Steerable catheter 200 may then be navigated to the region of interest and steering actuator 218 may be manipulated to cause a deflection in longitudinal axis 207. Medical procedure may then be performed at the region (or tissue) of interest. In embodiments where steerable catheter 200 is a navigated catheter, the method or procedure of guiding steerable catheter 200 of certain embodiments to a region (or tissue) of interest may comprise the additional steps of displaying an image of the region (or tissue) of interest and detecting a location and orientation of localization element 24. Then biopsy device 220 may be displayed, in real-time, on the image by superimposing a virtual representation of steerable catheter 200 and biopsy device 220 on the image based upon the location and orientation of localization element 24.
In one embodiment of the present invention, surgical instrument 12 (see
In accordance with one embodiment of the present invention and referring now to
A localization element 24 may be positioned at distal end portion 134 of elongate flexible shaft 130. In general any of a number of localization elements 24 may be used, including, but not limited to, for example, electromagnetic sensors, radiopaque markers visible via fluoroscopic imaging, or echogenic materials or patterns that increase visibility of the tip component under an ultrasonic beam. In this embodiment, localization element 24 comprises a six (6) degree of freedom (6DOF) electromagnetic sensor. In other embodiments, localization element 24 comprises a five (5) degree of freedom (5DOF) electromagnetic sensor. A localization element lead 103 extends from localization element 24 to proximal end portion 132 of elongate flexible shaft 130. In an alternative embodiment, localization element 24 and the electromagnetic field generator may be reversed, such that localization element 24 positioned at distal end portion 134 of elongate flexible shaft 130 emits a magnetic field that is sensed by external sensors.
Side exiting catheter 100 further comprises medical instrument 108 that may be extended from a position within outer wall 136 and through side exit 105 to a position outside outer wall 136 of elongate flexible shaft 130 by manipulation of handle 110. For ease of illustration, only the portion of medical instrument 108 that is extended outside elongate flexible shaft 130 appears in
In certain embodiments, by using localization element 24 (which in certain embodiments comprises a 6DOF sensor as described herein), the physician or other healthcare professional can have the location and direction of side exit 105 of elongate flexible shaft 130 displayed by surgical instrument navigation system 10. A real time two- or three-dimensional virtual reconstruction of side exit 105 and several centimeters of distal end portion 132 of elongate flexible shaft 130 may be displayed by surgical instrument navigation system 10. Visualization of the location and orientation of side exit 105 may allow for more intuitive advancement of side exiting catheter 100 to a region (or tissue) of interest. An image plane may be generated that is at side exit 105, as opposed to a point or position distal to distal end portion 134 of elongate flexible shaft 130. In certain embodiments, this may allow easier targeting of lesions, or other region(s) (or tissue) of interest, that may not be directly in the airway or other pathways, but rather partially or even completely outside of the airway or other pathways. In accordance with an exemplary method of using the device, side exiting catheter 100 may be steered slightly past the region (or tissue) of interest to align side exit 105. Medical instrument 108 (e.g., forceps, needle, brush, fiducial delivery device, etc.) may then be extended out elongate flexible shaft 130 through side exit 105. The directional aspect of distal end portion 134 and medical instrument 108 can be viewed on display 18 (see
In accordance with another embodiment, systems and methods may be used to provide the initial location of a localization element (e.g., an electromagnetic sensor) in a surgical instrument (e.g., a steerable surgical catheter, a side exiting catheter, a steering or shape sensing device such as a robotic articulating arm, fiber optic shape tracking device, or micro-actuator/flex systems, etc.). In one embodiment, a calibration jig system may be employed. The calibration jig system comprises at least three reference localization elements (e.g., electromagnetic sensors) positioned substantially in a plane and a tool/calibration channel may be positioned in a known location relative to the localization element plane. A surgical instrument may then be inserted into the tool/calibration channel and the surgical instrument pathway shape may be recorded along with the localization element(s) (e.g., 5DOF and/or 6DOF electromagnetic sensors) in the surgical instrument with respect to the location of the reference localization elements in the localization element plane. By using this calibration jig system, the alignment of the localization element(s) within the surgical instrument may be determined relative to the alignment of the surgical instrument. Additionally, or alternatively, other sensing mechanisms that report position and/or shape can be correlated relative to the reference localization element coordinates and therefore may define the complete or substantially complete physical coordinate system. Because the position of the jig tool channel is known relative to the position of the reference localization elements, the position of sensing mechanisms placed within the surgical instrument may be determined relative to the calibration jig and therefore relative to each other.
In certain embodiments, as illustrated in
Referring again to
In one embodiment, as illustrated by
Referring now to
In yet another embodiment, side exiting tip component 101 may comprise medical instrument 108 formed from a shape memory alloy which transitions between a first and second shape upon the application or release of stress. In certain embodiments, medical instrument 108 may be made of a superelastic material such as Nickel-Titanium (Ni—Ti) alloy (commercially available as nitinol) that has a martensitic to austenitic transformation temperature below body temperature and below normal room temperature. In other embodiments, other suitable shape memory materials for medical instrument 108 can include elastic biocompatible metals such as stainless steel, titanium, and tantalum or superelastic or psuedoelastic copper alloys, such as Cu—Al—Ni, Cu—Al—Zi, and Cu—Zi. When formed, medical instrument 108 comprising shape memory alloy will have a bend at a desired location with a bend angle (i.e., the first shape) and when housed within elongate flexible shaft 130, medical instrument 108 becomes relatively straight (i.e., the second shape). When medical instrument 108 is advanced and extends through side exit 105, the stress is removed and medical instrument 108 will return back to its preformed (first) shape. Accordingly, medical instrument 108 comprising shape memory alloy may be able to interact with regions (or tissues) of interest at additional angles than can be achieved the by a medical instrument 108 comprising a non-shape memory material extending through side exit 105. As illustrated in
In yet another embodiment, medical instrument 108 comprising shape memory alloy may be used with a catheter having an exit at the distal end, wherein medical instrument 108 exits the catheter along a longitudinal axis. By using a medical instrument comprising a shape memory alloy with a catheter having an exit along a longitudinal axis, a physician or other healthcare provider is able to target lesions, or other targets, that may not be directly in the airway or other pathways, but rather partially or even completely outside of the airway or other pathways. Such targeting may not be possible with a catheter having an exit at the distal end and non-shape memory instruments. Similar to
As shown by
As shown in
Typically, the outer diameter of elongate flexible shaft 130 of side exiting catheter 100 is less than 5 mm. By way of example, in certain embodiments, the outer diameter elongate flexible shaft 130 of side exiting catheter 100 is less than 1 mm. By way of further example, in certain embodiments, the outer diameter of elongate flexible shaft 130 of side exiting catheter 100 is less than 2 mm. By way of further example, in certain embodiments, the outer diameter of elongate flexible shaft 130 of side exiting catheter 100 is less than 3 mm. By way of further example, in certain embodiments, the outer diameter of elongate flexible shaft 130 of side exiting catheter 100 is less than 4 mm. By way of further example, in certain embodiments, the outer diameter of elongate flexible shaft 130 of side exiting catheter 100 is less than 5 mm.
However, in other embodiments, in addition to, or in place of, localization element 24, side exiting catheter 100 may be navigated wherein elongate flexible shaft 130 or medical instrument 108 may further comprise radiopaque markers visible via fluoroscopic imaging, or echogenic materials or patterns that increase visibility of the tip component under an ultrasonic beam. In yet other embodiments, side exiting catheter 100 may be navigated via other types of sensors, such as conductive localization elements, fiber optic localization elements, or any other type of localization element.
In one embodiment, side exiting tip component 101, illustrated by
As illustrated in
In yet another embodiment, at least one ring of radiopaque material 115 may surround side exit 105. By way of example, in one embodiment illustrated in
In certain embodiments, all or a portion of side exiting tip component 101 and/or distal end portion 134 of elongate flexible shaft 130 of side exiting catheter 100 may be echogenic such that it may be viewed via ultrasonic imaging. Several approaches of enhancing the ultrasonic signature of medical devices through modification of the device surface reflectivity are known in the prior art and can be applied to certain embodiments of the present invention. In one embodiment, an echogenic pattern can be positioned around the side exiting tip component 101 and/or around distal end portion 134 of elongate flexible shaft 130, such that the echogenic pattern covers the exterior circumference of side exiting tip component 101 and/or distal end portion 134 of elongate flexible shaft 130. Typically an echogenic pattern is on the exterior surface of side exiting tip component 101 defined as a length from the distal end of side exiting tip component 101 toward the proximal end of side exiting tip component 101. By way of example, in one embodiment, the echogenic pattern has a length of about 1 cm from the distal end of side exiting tip component 101. By way of further example, in another embodiment, the echogenic pattern has a length of about 2 cm from distal end of the side exiting tip component 101.
In one embodiment, as illustrated by
By way of further example, another embodiment of side exiting tip component 101 with an echogenic pattern is shown in
In certain embodiments, as shown in
In certain embodiments, as discussed herein, localization element 24 is positioned at or near distal end portion 134 of elongate flexible shaft 130. In one embodiment, as shown in
Another embodiment, with a radiopaque marker pattern positioned at or near the distal portion 134 of the elongate flexible shaft 130 is illustrated by
A method or procedure of guiding the side exiting catheter 100 of certain embodiments to a desired target tissue in the respiratory system of a patient may comprise displaying an image of the region of the patient, inserting a flexible lumen into the patient, and inserting into the flexible lumen side exiting catheter 100. Side exiting catheter 100 typically comprises an electromagnetic localization element at distal end portion 134. Side exiting catheter may then be navigated to the region of interest and the location and orientation of the electromagnetic localization element is detected. Then medical instrument 108 may be displayed, in real-time, on the image by superimposing a virtual representation of side exiting catheter 100 and medical instrument 108 on the image based upon the location and orientation of localization element 24. Then a medical procedure may be performed at the region (or tissue) of interest. In certain embodiments, side exiting catheter 100 further comprises an elongate flexible shaft 130 having a proximal end portion 132, an opposite distal end portion 134, a longitudinal axis 109, and an outer wall 136 comprising a biocompatible material extending from proximal end portion 132 to distal end portion 134. Side exiting catheter 100 may also comprise a handle 110 attached to proximal end portion 132, and a medical instrument 108 housed within distal end portion 134 of elongate flexible shaft 130 that is extendable along a path from a position within outer wall 136 through side exit 105 to a position outside outer wall 136 at an angle of at least 30 degrees relative to the longitudinal axis 109.
As illustrated in
As illustrated in
As shown in
Typically, biopsy device 220 may be extended a distance (extended distance) correlated to movement of handle 216 wherein extended distance may be from about 0.5 cm to about 4.0 cm. By way of example, in certain embodiments, the extended distance is at least about 0.5 cm. By way of further example, in certain embodiments, the extended distance is at least about 1.0 cm. By way of further example, in certain embodiments, the extended distance is at least about 1.5 cm. By way of further example, in certain embodiments, the extended distance is at least about 2.0 cm. By way of further example, in certain embodiments, the extended distance is at least about 2.5 cm. By way of further example, in certain embodiments, the extended distance is at least about 3.0 cm. By way of further example, in certain embodiments, the extended distance is at least about 3.5 cm. By way of further example, in certain embodiments, the extended distance is about 4.0 cm.
Typically, medical instrument 108 may be advanced a distance (advanced distance) correlated to movement of handle 110 wherein advanced distance may be from about 0.5 cm to about 4.0 cm. By way of example, in certain embodiments, the advanced distance is at least about 0.5 cm. By way of further example, in certain embodiments, the advanced distance is at least about 1.0 cm. By way of further example, in certain embodiments, the advanced distance is at least about 1.5 cm. By way of further example, in certain embodiments, the advanced distance is at least about 2.0 cm. By way of further example, in certain embodiments, the advanced distance is at least about 2.5 cm. By way of further example, in certain embodiments, the advanced distance is at least about 3.0 cm. By way of further example, in certain embodiments, the advanced distance is at least about 3.5 cm. By way of further example, in certain embodiments, the advanced distance is about 4.0 cm.
In another embodiment, as shown in
Other embodiments include, for example, a plastic or polymer sheath or condom that is custom sized to fit over an existing, non-navigated surgical instrument or device 70 and may be placed over a localization element lead wire 103 and localization element 24 to add a localization element 24 (e.g., an electromagnetic sensor), thus converting existing, non-navigated surgical instrument or device 70 to a navigated surgical instrument or device 70. In this embodiment, the plastic or polymer sheath or condom may be held in place on the existing, non-navigated surgical instrument or device 70 by a friction fit. In yet other embodiments, an elastic or stretchable plastic or polymer sheath or condom may be expanded and placed over a localization element lead wire 103 and localization element 24 to add a localization element 24 (e.g., an electromagnetic sensor), thus converting the existing, non-navigated surgical instrument or device 70 to a navigated surgical instrument or device 70. In this embodiment, the elastic or stretchable plastic or polymer sheath or condom may also be held in place on the existing, non-navigated surgical instrument or device 70 by a friction fit.
In yet other embodiments, a localization element 24 may be affixed to an existing, non-navigated surgical instrument or device 70 with tape. In certain embodiments, localization element 24 may be wireless. In other embodiments, localization element 24 may be affixed to an existing, non-navigated surgical instrument or device 70 via an adhesive.
In addition to or in place of localization element 24, steerable catheter 200 and/or side exiting catheter 100 may be equipped with one or more sensing devices at or near the distal end portion of the elongate flexible shaft and/or at the biopsy device 220 or medical instrument 108 of the respective catheters described herein. Additional sensing devices may include electrodes for sensing depolarization signals occurring in excitable tissue such as the heart, nerve or brain. In one embodiment, for use in cardiac applications, the sensing device may include at least one electrode for sensing internal cardiac electrogram (EGM) signals. In other embodiments, the sensing device may be an absolute pressure sensor to monitor blood pressure. In still other embodiments, surgical instrument 12 may be equipped with other sensing devices including physiological detection devices, localization elements, temperature sensors, motion sensors, optical coherence tomography (OCT) sensors, endobronchial ultrasound (EBUS) sensors, or Doppler or ultrasound sensors that can detect the presence or absence of blood vessels.
The accompanying Figures and this description depict and describe certain embodiments of a navigation system (and related methods and devices) in accordance with the present invention, and features and components thereof. It should also be noted that any references herein to front and back, right and left, top and bottom and upper and lower are intended for convenience of description, not to limit the present invention or its components to any one positional or spatial orientation.
It is noted that the terms “comprise” (and any form of comprise, such as “comprises” and “comprising”), “have” (and any form of have, such as “has” and “having”), “contain” (and any form of contain, such as “contains” and “containing”), and “include” (and any form of include, such as “includes” and “including”) are open-ended linking verbs. Thus, a method, an apparatus, or a system that “comprises,” “has,” “contains,” or “includes” one or more items possesses at least those one or more items, but is not limited to possessing only those one or more items
Individual elements or steps of the present methods, apparatuses, and systems are to be treated in the same manner. Thus, a step that calls for modifying a segmented image dataset for a region of a respiratory system to match the corresponding anatomy of a patient's respiratory system, that includes the steps of: (i) forming a respiratory-gated point cloud of data that demarcates anatomical features in a region of a patient's respiratory system at one or more discrete phases within a respiration cycle of a patient, (ii) density filtering the respiratory-gated point cloud, (iii) classifying the density filtered respiratory-gated point cloud according to anatomical points of reference in a segmented image dataset for the region of the patient's respiratory system, and (iv) modifying the segmented image dataset to correspond to the classified anatomical points of reference in the density filtered respiratory-gated point cloud, but also covers the steps of (i) comparing the registered respiratory-gated point cloud to a segmented image dataset to determine the weighting of points comprised by the classified respiratory-gated point cloud, (ii) distinguishing regions of greater weighting from regions of lesser weighting, and (iii) modifying the segmented image dataset to correspond to the classified respiratory-gated point cloud.
The terms “a” and “an” are defined as one or more than one. The term “another” is defined as at least a second or more. The term “coupled” encompasses both direct and indirect connections, and is not limited to mechanical connections.
Those of skill in the art will appreciate that in the detailed description above, certain well known components and assembly techniques have been omitted so that the present methods, apparatuses, and systems are not obscured in unnecessary detail.
While various embodiments of the invention have been described above, it should be understood that they have been presented by way of example only, and not limitation. Thus, the breadth and scope of the invention should not be limited by any of the above-described embodiments, but should be defined only in accordance with the following claims and their equivalents.
The previous description of the embodiments is provided to enable any person skilled in the art to make or use the invention. While the invention has been particularly shown and described with reference to embodiments thereof, it will be understood by those skilled in art that various changes in form and details may be made therein without departing from the spirit and scope of the invention. For example, the elongate flexible shafts, biopsy device, medical instruments, and localization elements can be constructed from any suitable material, and can be a variety of different shapes and sizes, not necessarily specifically illustrated, while still remaining within the scope of the invention.
| Number | Name | Date | Kind |
|---|---|---|---|
| 3788324 | Lim | Jan 1974 | A |
| 4421106 | Uehara | Dec 1983 | A |
| 4583538 | Onik | Apr 1986 | A |
| 4593680 | Kubokawa | Jun 1986 | A |
| 5053042 | Bidwell | Oct 1991 | A |
| 5081997 | Bosley, Jr. et al. | Jan 1992 | A |
| 5103488 | Gemello et al. | Apr 1992 | A |
| 5158088 | Nelson et al. | Oct 1992 | A |
| 5186174 | Schlondorff | Feb 1993 | A |
| 5238804 | Maskasky et al. | Aug 1993 | A |
| 5251165 | James, III | Oct 1993 | A |
| 5251635 | Dumoulin et al. | Oct 1993 | A |
| 5265610 | Darrow et al. | Nov 1993 | A |
| 5295493 | Radisch, Jr. | Mar 1994 | A |
| 5348011 | Nessaiver | Sep 1994 | A |
| 5359513 | Kano et al. | Oct 1994 | A |
| 5377678 | Dumoulin et al. | Jan 1995 | A |
| 5391199 | Ben-haim | Feb 1995 | A |
| 5437292 | Kipshidze et al. | Aug 1995 | A |
| 5483691 | Heck et al. | Jan 1996 | A |
| 5483961 | Kelly | Jan 1996 | A |
| 5577502 | Darrow et al. | Nov 1996 | A |
| 5581183 | Lindstedt et al. | Dec 1996 | A |
| 5644612 | Moorman et al. | Jul 1997 | A |
| 5671739 | Darrow et al. | Sep 1997 | A |
| 5674498 | Inoue et al. | Oct 1997 | A |
| 5718241 | Ben-haim | Feb 1998 | A |
| 5730129 | Darrow et al. | Mar 1998 | A |
| 5740080 | Shook | Apr 1998 | A |
| 5740808 | Panescu et al. | Apr 1998 | A |
| 5765561 | Chen et al. | Jun 1998 | A |
| 5769789 | Wang et al. | Jun 1998 | A |
| 5769861 | Vilsmeier | Jun 1998 | A |
| 5771306 | Stork et al. | Jun 1998 | A |
| 5787886 | Kelly et al. | Aug 1998 | A |
| 5803089 | Ferre et al. | Sep 1998 | A |
| 5814022 | Antanavich et al. | Sep 1998 | A |
| 5814066 | Spotnitz | Sep 1998 | A |
| 5833608 | Acker | Nov 1998 | A |
| 5840025 | Ben-haim | Nov 1998 | A |
| 5868673 | Vesely | Feb 1999 | A |
| 5873817 | Kokish | Feb 1999 | A |
| 5928248 | Acker | Jul 1999 | A |
| 5951461 | Nyo | Sep 1999 | A |
| 5978696 | Vomlehn et al. | Nov 1999 | A |
| 6016439 | Acker | Jan 2000 | A |
| 6019724 | Gronningsaeter | Feb 2000 | A |
| 6026173 | Svenson | Feb 2000 | A |
| 6078175 | Foo | Jun 2000 | A |
| 6122538 | Sliwa, Jr. et al. | Sep 2000 | A |
| 6122541 | Cosman et al. | Sep 2000 | A |
| 6129508 | Bahr et al. | Oct 2000 | A |
| 6132396 | Antanavich et al. | Oct 2000 | A |
| 6139508 | Simpson et al. | Oct 2000 | A |
| 6144875 | Schweikard et al. | Nov 2000 | A |
| 6167296 | Shahidi | Dec 2000 | A |
| 6173201 | Front | Jan 2001 | B1 |
| 6188355 | Gilboa | Feb 2001 | B1 |
| 6198959 | Wang | Mar 2001 | B1 |
| 6201987 | Dumoulin | Mar 2001 | B1 |
| 6226543 | Gilboa et al. | May 2001 | B1 |
| 6226548 | Foley et al. | May 2001 | B1 |
| 6233476 | Strommer et al. | May 2001 | B1 |
| 6235038 | Hunter et al. | May 2001 | B1 |
| 6236875 | Bucholz et al. | May 2001 | B1 |
| 6246896 | Dumoulin et al. | Jun 2001 | B1 |
| 6246898 | Vesely et al. | Jun 2001 | B1 |
| 6253770 | Acker et al. | Jul 2001 | B1 |
| 6254550 | Mcnamara et al. | Jul 2001 | B1 |
| 6267769 | Truwit | Jul 2001 | B1 |
| 6275560 | Blake et al. | Aug 2001 | B1 |
| 6282442 | Destefano et al. | Aug 2001 | B1 |
| 6285902 | Kienzle, III et al. | Sep 2001 | B1 |
| 6298259 | Kucharczyk | Oct 2001 | B1 |
| 6314310 | Ben-haim | Nov 2001 | B1 |
| 6314311 | Williams et al. | Nov 2001 | B1 |
| 6314312 | Wessels et al. | Nov 2001 | B1 |
| 6317616 | Glossop | Nov 2001 | B1 |
| 6317619 | Boernert et al. | Nov 2001 | B1 |
| 6330356 | Sundareswaran et al. | Dec 2001 | B1 |
| 6332089 | Acker et al. | Dec 2001 | B1 |
| 6332891 | Himes | Dec 2001 | B1 |
| 6335617 | Osadchy et al. | Jan 2002 | B1 |
| 6335623 | Damadian et al. | Jan 2002 | B1 |
| 6340363 | Bolger et al. | Jan 2002 | B1 |
| 6347240 | Foley et al. | Feb 2002 | B1 |
| 6348058 | Melkent et al. | Feb 2002 | B1 |
| 6351573 | Schneider | Feb 2002 | B1 |
| 6351659 | Vilsmeier | Feb 2002 | B1 |
| 6361759 | Frayne et al. | Mar 2002 | B1 |
| 6362821 | Gibson et al. | Mar 2002 | B1 |
| 6368331 | Front et al. | Apr 2002 | B1 |
| 6369571 | Damadian et al. | Apr 2002 | B1 |
| 6369574 | Ederlöv et al. | Apr 2002 | B1 |
| 6373998 | Thirion et al. | Apr 2002 | B2 |
| 6379302 | Kessman | Apr 2002 | B1 |
| 6380732 | Gilboa | Apr 2002 | B1 |
| 6381485 | Hunter et al. | Apr 2002 | B1 |
| 6402762 | Hunter et al. | Jun 2002 | B2 |
| 6418238 | Shiratani et al. | Jul 2002 | B1 |
| 6421551 | Kuth et al. | Jul 2002 | B1 |
| 6424856 | Vilsmeier et al. | Jul 2002 | B1 |
| 6425865 | Salcudean et al. | Jul 2002 | B1 |
| 6430430 | Gosche | Aug 2002 | B1 |
| 6434415 | Foley et al. | Aug 2002 | B1 |
| 6434507 | Clayton et al. | Aug 2002 | B1 |
| 6437571 | Danby et al. | Aug 2002 | B1 |
| 6442417 | Shahidi et al. | Aug 2002 | B1 |
| 6445186 | Damadian et al. | Sep 2002 | B1 |
| 6445943 | Ferre et al. | Sep 2002 | B1 |
| 6455182 | Silver | Sep 2002 | B1 |
| 6461372 | Jensen et al. | Oct 2002 | B1 |
| 6468265 | Evans et al. | Oct 2002 | B1 |
| 6469508 | Damadian et al. | Oct 2002 | B1 |
| 6470066 | Takagi et al. | Oct 2002 | B2 |
| 6470207 | Simon et al. | Oct 2002 | B1 |
| 6473635 | Rasche | Oct 2002 | B1 |
| 6477400 | Barrick | Nov 2002 | B1 |
| 6478793 | Cosman et al. | Nov 2002 | B1 |
| 6478802 | Kienzle, III et al. | Nov 2002 | B2 |
| 6483948 | Spink et al. | Nov 2002 | B1 |
| 6484049 | Seeley et al. | Nov 2002 | B1 |
| 6485413 | Boppart et al. | Nov 2002 | B1 |
| D466609 | Glossop | Dec 2002 | S |
| D466610 | Ashton et al. | Dec 2002 | S |
| 6490467 | Bucholz et al. | Dec 2002 | B1 |
| 6490475 | Seeley et al. | Dec 2002 | B1 |
| 6490477 | Zylka et al. | Dec 2002 | B1 |
| 6491699 | Henderson et al. | Dec 2002 | B1 |
| 6491702 | Heilbrun et al. | Dec 2002 | B2 |
| 6493574 | Ehnholm et al. | Dec 2002 | B1 |
| 6496007 | Damadian et al. | Dec 2002 | B1 |
| 6498944 | Ben-haim et al. | Dec 2002 | B1 |
| 6501981 | Schweikard et al. | Dec 2002 | B1 |
| 6504893 | Flohr et al. | Jan 2003 | B1 |
| 6504894 | Pan et al. | Jan 2003 | B2 |
| 6516213 | Nevo | Feb 2003 | B1 |
| 6517485 | Olstad et al. | Feb 2003 | B2 |
| 6527443 | Vilsmeier et al. | Mar 2003 | B1 |
| 6535756 | Simon et al. | Mar 2003 | B1 |
| 6538634 | Chui et al. | Mar 2003 | B1 |
| 6539127 | Roche et al. | Mar 2003 | B1 |
| 6541947 | Dittmer et al. | Apr 2003 | B1 |
| 6541973 | Danby et al. | Apr 2003 | B1 |
| 6544041 | Damadian | Apr 2003 | B1 |
| 6547782 | Taylor | Apr 2003 | B1 |
| 6558333 | Gilboa et al. | May 2003 | B2 |
| 6562059 | Edwards et al. | May 2003 | B2 |
| 6567687 | Front et al. | May 2003 | B2 |
| 6580938 | Acker | Jun 2003 | B1 |
| 6584174 | Schubert et al. | Jun 2003 | B2 |
| 6584339 | Galloway, Jr. et al. | Jun 2003 | B2 |
| 6591130 | Shahidi | Jul 2003 | B2 |
| 6593884 | Gilboa et al. | Jul 2003 | B1 |
| 6606513 | Lardo et al. | Aug 2003 | B2 |
| 6609022 | Vilsmeier et al. | Aug 2003 | B2 |
| 6615155 | Gilboa | Sep 2003 | B2 |
| 6636757 | Jascob et al. | Oct 2003 | B1 |
| 6650924 | Kuth et al. | Nov 2003 | B2 |
| 6666579 | Jensen | Dec 2003 | B2 |
| 6674833 | Shahidi et al. | Jan 2004 | B2 |
| 6675032 | Chen et al. | Jan 2004 | B2 |
| 6675033 | Lardo et al. | Jan 2004 | B1 |
| 6687531 | Ferre et al. | Feb 2004 | B1 |
| 6690960 | Chen et al. | Feb 2004 | B2 |
| 6694167 | Ferre et al. | Feb 2004 | B1 |
| 6697664 | Kienzle, III et al. | Feb 2004 | B2 |
| 6702780 | Gilboa et al. | Mar 2004 | B1 |
| 6711429 | Gilboa et al. | Mar 2004 | B1 |
| 6714629 | Vilsmeier | Mar 2004 | B2 |
| 6714810 | Grzeszczuk et al. | Mar 2004 | B2 |
| 6723207 | Laser | Apr 2004 | B2 |
| 6725080 | Melkent et al. | Apr 2004 | B2 |
| 6738656 | Ferre et al. | May 2004 | B1 |
| 6774624 | Anderson et al. | Aug 2004 | B2 |
| 6782287 | Grzeszczuk et al. | Aug 2004 | B2 |
| 6796988 | Melkent et al. | Sep 2004 | B2 |
| 6799569 | Danielsson et al. | Oct 2004 | B2 |
| 6823207 | Jensen et al. | Nov 2004 | B1 |
| 6826423 | Hardy et al. | Nov 2004 | B1 |
| 6833814 | Gilboa et al. | Dec 2004 | B2 |
| 6850794 | Shahidi | Feb 2005 | B2 |
| 6856826 | Seeley et al. | Feb 2005 | B2 |
| 6856827 | Seeley et al. | Feb 2005 | B2 |
| 6892090 | Verard et al. | May 2005 | B2 |
| 6898303 | Armato, III et al. | May 2005 | B2 |
| 6899672 | Chin et al. | May 2005 | B2 |
| 6907281 | Grzeszczuk | Jun 2005 | B2 |
| 6920347 | Simon et al. | Jul 2005 | B2 |
| 6925200 | Wood et al. | Aug 2005 | B2 |
| 6934575 | Ferre et al. | Aug 2005 | B2 |
| 6947788 | Gilboa et al. | Sep 2005 | B2 |
| 6968224 | Kessman et al. | Nov 2005 | B2 |
| 6978166 | Foley et al. | Dec 2005 | B2 |
| 6982090 | Gillespie | Jan 2006 | B2 |
| 6989303 | Mori | Jan 2006 | B2 |
| 6992477 | Govari | Jan 2006 | B2 |
| 6996430 | Gilboa et al. | Feb 2006 | B1 |
| 7015859 | Anderson | Mar 2006 | B2 |
| 7015907 | Tek et al. | Mar 2006 | B2 |
| 7035683 | Guendel | Apr 2006 | B2 |
| 7050845 | Vilsmeier | May 2006 | B2 |
| 7115100 | Mcrury et al. | Oct 2006 | B2 |
| 7130700 | Gardeski | Oct 2006 | B2 |
| 7139601 | Bucholz et al. | Nov 2006 | B2 |
| 7153297 | Peterson | Dec 2006 | B2 |
| 7171257 | Thomson | Jan 2007 | B2 |
| 7174201 | Govari et al. | Feb 2007 | B2 |
| 7233820 | Gilboa | Jun 2007 | B2 |
| 7260426 | Schweikard et al. | Aug 2007 | B2 |
| 7300428 | Ingenito | Nov 2007 | B2 |
| 7339587 | Kropfeld | Mar 2008 | B2 |
| 7357807 | Donohoe et al. | Apr 2008 | B2 |
| 7366562 | Dukesherer et al. | Apr 2008 | B2 |
| 7371067 | Anderson et al. | May 2008 | B2 |
| 7398116 | Edwards | Jul 2008 | B2 |
| 7481805 | Magnusson | Jan 2009 | B2 |
| 7505806 | Masutani et al. | Mar 2009 | B2 |
| 7555330 | Gilboa et al. | Jun 2009 | B2 |
| 7594925 | Danek et al. | Sep 2009 | B2 |
| 7599730 | Hunter et al. | Oct 2009 | B2 |
| 7641609 | Ohnishi et al. | Jan 2010 | B2 |
| 7659912 | Akimoto et al. | Feb 2010 | B2 |
| 7697972 | Verard et al. | Apr 2010 | B2 |
| 7708712 | Phan et al. | May 2010 | B2 |
| 7756563 | Higgins et al. | Jul 2010 | B2 |
| 7778691 | Zhang et al. | Aug 2010 | B2 |
| 7835493 | Keall et al. | Nov 2010 | B2 |
| 7889905 | Higgins et al. | Feb 2011 | B2 |
| 7901348 | Soper et al. | Mar 2011 | B2 |
| 7949385 | Khamene et al. | May 2011 | B2 |
| 7962193 | Edwards et al. | Jun 2011 | B2 |
| 7969143 | Gilboa | Jun 2011 | B2 |
| 7979244 | Fang et al. | Jul 2011 | B2 |
| 7985187 | Wibowo et al. | Jul 2011 | B2 |
| 7988639 | Starks | Aug 2011 | B2 |
| 7998062 | Gilboa | Aug 2011 | B2 |
| 8002465 | Ahn | Aug 2011 | B2 |
| 8016749 | Clerc et al. | Sep 2011 | B2 |
| 8046052 | Verard et al. | Oct 2011 | B2 |
| 8049777 | Akimoto et al. | Nov 2011 | B2 |
| 8064669 | Higgins et al. | Nov 2011 | B2 |
| 8088126 | Fugo | Jan 2012 | B2 |
| 8096957 | Conquergood et al. | Jan 2012 | B2 |
| 8102416 | Ito et al. | Jan 2012 | B2 |
| 8150138 | Ohnishi | Apr 2012 | B2 |
| 8150495 | Edwards et al. | Apr 2012 | B2 |
| 8199988 | Marshall et al. | Jun 2012 | B2 |
| 8202213 | Ito et al. | Jun 2012 | B2 |
| 8214015 | Macaulay et al. | Jul 2012 | B2 |
| 8218846 | Trumer et al. | Jul 2012 | B2 |
| 8218847 | Averbuch et al. | Jul 2012 | B2 |
| 8219179 | Ganatra et al. | Jul 2012 | B2 |
| 8229188 | Rusko et al. | Jul 2012 | B2 |
| 8311303 | Suehling et al. | Nov 2012 | B2 |
| 8311307 | Kitamura | Nov 2012 | B2 |
| 8317149 | Greenburg et al. | Nov 2012 | B2 |
| 8317726 | Timberlake et al. | Nov 2012 | B2 |
| 8382662 | Soper et al. | Feb 2013 | B2 |
| 8428328 | Averbuch et al. | Apr 2013 | B2 |
| 8452062 | Gogin et al. | May 2013 | B2 |
| 8468003 | Gibbs et al. | Jun 2013 | B2 |
| 8473032 | Averbuch | Jun 2013 | B2 |
| 8483801 | Edwards | Jul 2013 | B2 |
| 8494246 | Trumer et al. | Jul 2013 | B2 |
| 8494612 | Vetter et al. | Jul 2013 | B2 |
| 8515133 | Kitamura | Aug 2013 | B2 |
| 8611983 | Glossop | Dec 2013 | B2 |
| 8611984 | Greenburg et al. | Dec 2013 | B2 |
| 8632461 | Glossop | Jan 2014 | B2 |
| 8672836 | Higgins et al. | Mar 2014 | B2 |
| 8675935 | Higgins et al. | Mar 2014 | B2 |
| 8696548 | Gilboa | Apr 2014 | B2 |
| 8696685 | Gilboa | Apr 2014 | B2 |
| 8700132 | Ganatra et al. | Apr 2014 | B2 |
| 8793107 | Miller et al. | Jul 2014 | B2 |
| 8965108 | Chabanas | Feb 2015 | B2 |
| 9138165 | Holsing et al. | Sep 2015 | B2 |
| 9171377 | Kabus et al. | Oct 2015 | B2 |
| 9265468 | Rai et al. | Feb 2016 | B2 |
| 9271803 | Averbuch et al. | Mar 2016 | B2 |
| 9390552 | Huang | Jul 2016 | B1 |
| 9404734 | Ramamurthy | Aug 2016 | B2 |
| 10460437 | Holsing | Oct 2019 | B2 |
| 11413086 | Hoey | Aug 2022 | B2 |
| 11551359 | Holsing | Jan 2023 | B2 |
| 20010007918 | Vilsmeier et al. | Jul 2001 | A1 |
| 20010025142 | Wessels et al. | Sep 2001 | A1 |
| 20010029333 | Shahidi | Oct 2001 | A1 |
| 20010031919 | Strommer et al. | Oct 2001 | A1 |
| 20010031985 | Gilboa et al. | Oct 2001 | A1 |
| 20010036245 | Kienzle, III et al. | Nov 2001 | A1 |
| 20010041835 | Front et al. | Nov 2001 | A1 |
| 20020017515 | Obata | Feb 2002 | A1 |
| 20020044631 | Graumann et al. | Apr 2002 | A1 |
| 20020045812 | Ben-haim et al. | Apr 2002 | A1 |
| 20020049375 | Strommer et al. | Apr 2002 | A1 |
| 20020049378 | Grzeszczuk et al. | Apr 2002 | A1 |
| 20020070970 | Wood et al. | Jun 2002 | A1 |
| 20020075994 | Shahidi et al. | Jun 2002 | A1 |
| 20020077543 | Grzeszczuk et al. | Jun 2002 | A1 |
| 20020077544 | Shahidi | Jun 2002 | A1 |
| 20020082492 | Grzeszczuk | Jun 2002 | A1 |
| 20020085681 | Jensen | Jul 2002 | A1 |
| 20020143317 | Glossop | Oct 2002 | A1 |
| 20020161295 | Edwards et al. | Oct 2002 | A1 |
| 20020193685 | Mate et al. | Dec 2002 | A1 |
| 20030000535 | Galloway, Jr. et al. | Jan 2003 | A1 |
| 20030004411 | Govari et al. | Jan 2003 | A1 |
| 20030016852 | Kaufman et al. | Jan 2003 | A1 |
| 20030018251 | Solomon | Jan 2003 | A1 |
| 20030023161 | Govari et al. | Jan 2003 | A1 |
| 20030028091 | Simon et al. | Feb 2003 | A1 |
| 20030029464 | Chen et al. | Feb 2003 | A1 |
| 20030032878 | Shahidi | Feb 2003 | A1 |
| 20030032936 | Lederman | Feb 2003 | A1 |
| 20030049667 | Wen-tung et al. | Mar 2003 | A1 |
| 20030051733 | Kotmel et al. | Mar 2003 | A1 |
| 20030074011 | Gilboa et al. | Apr 2003 | A1 |
| 20030088179 | Seeley et al. | May 2003 | A1 |
| 20030114749 | Rahn | Jun 2003 | A1 |
| 20030125622 | Schweikard et al. | Jul 2003 | A1 |
| 20030130576 | Seeley et al. | Jul 2003 | A1 |
| 20030139663 | Graumann | Jul 2003 | A1 |
| 20030199785 | Hibner et al. | Oct 2003 | A1 |
| 20030208116 | Liang et al. | Nov 2003 | A1 |
| 20030208122 | Melkent et al. | Nov 2003 | A1 |
| 20030216631 | Bloch et al. | Nov 2003 | A1 |
| 20030220557 | Cleary et al. | Nov 2003 | A1 |
| 20040006268 | Gilboa et al. | Jan 2004 | A1 |
| 20040013548 | Seto et al. | Jan 2004 | A1 |
| 20040034300 | Verard et al. | Feb 2004 | A1 |
| 20040044350 | Martin et al. | Mar 2004 | A1 |
| 20040049121 | Yaron | Mar 2004 | A1 |
| 20040076259 | Jensen et al. | Apr 2004 | A1 |
| 20040091143 | Hu | May 2004 | A1 |
| 20040092815 | Schweikard et al. | May 2004 | A1 |
| 20040097805 | Verard et al. | May 2004 | A1 |
| 20040097806 | Hunter et al. | May 2004 | A1 |
| 20040097965 | Gardeski | May 2004 | A1 |
| 20040116803 | Jascob et al. | Jun 2004 | A1 |
| 20040122311 | Cosman | Jun 2004 | A1 |
| 20040138548 | Strommer et al. | Jul 2004 | A1 |
| 20040152970 | Hunter et al. | Aug 2004 | A1 |
| 20040152974 | Solomon | Aug 2004 | A1 |
| 20040167393 | Solar et al. | Aug 2004 | A1 |
| 20040193042 | Scampini et al. | Sep 2004 | A1 |
| 20040210125 | Chen et al. | Oct 2004 | A1 |
| 20040249267 | Gilboa | Dec 2004 | A1 |
| 20050010099 | Raabe et al. | Jan 2005 | A1 |
| 20050020900 | Yngvesson et al. | Jan 2005 | A1 |
| 20050027186 | Chen et al. | Feb 2005 | A1 |
| 20050033149 | Strommer et al. | Feb 2005 | A1 |
| 20050065433 | Anderson | Mar 2005 | A1 |
| 20050085718 | Shahidi | Apr 2005 | A1 |
| 20050085793 | Glossop | Apr 2005 | A1 |
| 20050107679 | Geiger et al. | May 2005 | A1 |
| 20050107688 | Strommer | May 2005 | A1 |
| 20050113809 | Melkent et al. | May 2005 | A1 |
| 20050137661 | Sra | Jun 2005 | A1 |
| 20050143651 | Verard et al. | Jun 2005 | A1 |
| 20050169510 | Zuhars et al. | Aug 2005 | A1 |
| 20050182295 | Soper et al. | Aug 2005 | A1 |
| 20050182319 | Glossop | Aug 2005 | A1 |
| 20050187482 | O'brien et al. | Aug 2005 | A1 |
| 20050197568 | Vass et al. | Sep 2005 | A1 |
| 20050203368 | Verin | Sep 2005 | A1 |
| 20050203383 | Moctezuma De La Barrera | Sep 2005 | A1 |
| 20050203413 | Fichtinger et al. | Sep 2005 | A1 |
| 20050216237 | Adachi | Sep 2005 | A1 |
| 20050234335 | Simon et al. | Oct 2005 | A1 |
| 20050288574 | Thornton et al. | Dec 2005 | A1 |
| 20050288578 | Durlak | Dec 2005 | A1 |
| 20060004281 | Saracen | Jan 2006 | A1 |
| 20060025677 | Verard et al. | Feb 2006 | A1 |
| 20060045318 | Schoisswohl et al. | Mar 2006 | A1 |
| 20060050942 | Bertram et al. | Mar 2006 | A1 |
| 20060050988 | Kraus et al. | Mar 2006 | A1 |
| 20060058647 | Strommer et al. | Mar 2006 | A1 |
| 20060063998 | Von Jako et al. | Mar 2006 | A1 |
| 20060064006 | Strommer et al. | Mar 2006 | A1 |
| 20060074292 | Thomson et al. | Apr 2006 | A1 |
| 20060074299 | Sayeh | Apr 2006 | A1 |
| 20060074304 | Sayeh | Apr 2006 | A1 |
| 20060079759 | Vaillant et al. | Apr 2006 | A1 |
| 20060084867 | Tremblay et al. | Apr 2006 | A1 |
| 20060093089 | Vertatschitsch et al. | May 2006 | A1 |
| 20060094958 | Marquart et al. | May 2006 | A1 |
| 20060106292 | Anderson | May 2006 | A1 |
| 20060116634 | Shachar | Jun 2006 | A1 |
| 20060122497 | Glossop | Jun 2006 | A1 |
| 20060135961 | Rosenman et al. | Jun 2006 | A1 |
| 20060142798 | Holman et al. | Jun 2006 | A1 |
| 20060173269 | Glossop | Aug 2006 | A1 |
| 20060173291 | Glossop | Aug 2006 | A1 |
| 20060184016 | Glossop | Aug 2006 | A1 |
| 20060189867 | Revie | Aug 2006 | A1 |
| 20060247511 | Anderson | Nov 2006 | A1 |
| 20060258933 | Ellis et al. | Nov 2006 | A1 |
| 20060270976 | Savage | Nov 2006 | A1 |
| 20070032723 | Glossop | Feb 2007 | A1 |
| 20070038058 | West et al. | Feb 2007 | A1 |
| 20070066887 | Mire et al. | Mar 2007 | A1 |
| 20070110289 | Fu et al. | May 2007 | A1 |
| 20070129629 | Beauregard et al. | Jun 2007 | A1 |
| 20070135803 | Belson | Jun 2007 | A1 |
| 20070167714 | Kiraly et al. | Jul 2007 | A1 |
| 20070167738 | Timinger et al. | Jul 2007 | A1 |
| 20070167744 | Beauregard et al. | Jul 2007 | A1 |
| 20070197896 | Moll et al. | Aug 2007 | A1 |
| 20070219059 | Schwartz et al. | Sep 2007 | A1 |
| 20070225559 | Clerc et al. | Sep 2007 | A1 |
| 20070232896 | Gilboa et al. | Oct 2007 | A1 |
| 20070244355 | Shaw | Oct 2007 | A1 |
| 20070249896 | Goldfarb et al. | Oct 2007 | A1 |
| 20070270679 | Nguyen | Nov 2007 | A1 |
| 20070276180 | Greenburg et al. | Nov 2007 | A1 |
| 20070293721 | Gilboa | Dec 2007 | A1 |
| 20080071142 | Gattani et al. | Mar 2008 | A1 |
| 20080071143 | Gattani et al. | Mar 2008 | A1 |
| 20080097187 | Gielen et al. | Apr 2008 | A1 |
| 20080118135 | Averbuch et al. | May 2008 | A1 |
| 20080125760 | Gilboa | May 2008 | A1 |
| 20080132757 | Tgavalekos | Jun 2008 | A1 |
| 20080140114 | Edwards et al. | Jun 2008 | A1 |
| 20080167639 | Gilboa | Jul 2008 | A1 |
| 20080183071 | Strommer et al. | Jul 2008 | A1 |
| 20080221442 | Tolkowsky et al. | Sep 2008 | A1 |
| 20080247622 | Aylward et al. | Oct 2008 | A1 |
| 20080255416 | Gilboa | Oct 2008 | A1 |
| 20080262297 | Gilboa et al. | Oct 2008 | A1 |
| 20080262342 | Averbruch | Oct 2008 | A1 |
| 20080262430 | Anderson et al. | Oct 2008 | A1 |
| 20080269561 | Banik et al. | Oct 2008 | A1 |
| 20080287803 | Li et al. | Nov 2008 | A1 |
| 20090054908 | Zand et al. | Feb 2009 | A1 |
| 20090062789 | Rioux et al. | Mar 2009 | A1 |
| 20090088600 | Meloul | Apr 2009 | A1 |
| 20090156895 | Higgins | Jun 2009 | A1 |
| 20090156951 | Averbuch | Jun 2009 | A1 |
| 20090209817 | Averbuch | Aug 2009 | A1 |
| 20090227861 | Ganatra et al. | Sep 2009 | A1 |
| 20090240140 | Fitelzon et al. | Sep 2009 | A1 |
| 20090240198 | Averbuch | Sep 2009 | A1 |
| 20090262979 | Markowitz | Oct 2009 | A1 |
| 20090284255 | Zur | Nov 2009 | A1 |
| 20090306644 | Mayse et al. | Dec 2009 | A1 |
| 20100016757 | Greenburg et al. | Jan 2010 | A1 |
| 20100036241 | Mayse et al. | Feb 2010 | A1 |
| 20100041949 | Tolkowsky | Feb 2010 | A1 |
| 20100137707 | Hunter et al. | Jun 2010 | A1 |
| 20100160733 | Gilboa | Jun 2010 | A1 |
| 20100217072 | Kondoh | Aug 2010 | A1 |
| 20110054304 | Markowitz et al. | Mar 2011 | A1 |
| 20110054309 | Edwards | Mar 2011 | A1 |
| 20110058721 | Zhang et al. | Mar 2011 | A1 |
| 20110102432 | Melkisetoglu et al. | May 2011 | A1 |
| 20110118593 | Melkent et al. | May 2011 | A1 |
| 20110152880 | Alvarez | Jun 2011 | A1 |
| 20110158488 | Cohen et al. | Jun 2011 | A1 |
| 20110190660 | Levy | Aug 2011 | A1 |
| 20110301587 | Deem et al. | Dec 2011 | A1 |
| 20120046521 | Hunter et al. | Feb 2012 | A1 |
| 20120059220 | Holsing et al. | Mar 2012 | A1 |
| 20120059248 | Holsing et al. | Mar 2012 | A1 |
| 20120065481 | Hunter et al. | Mar 2012 | A1 |
| 20120071753 | Hunter et al. | Mar 2012 | A1 |
| 20120123296 | Hashimshony et al. | May 2012 | A1 |
| 20120275689 | Birtwistle | Nov 2012 | A1 |
| 20130184569 | Strommer et al. | Jul 2013 | A1 |
| 20140343408 | Tolkowsky | Nov 2014 | A1 |
| Number | Date | Country |
|---|---|---|
| 4102211 | Aug 1991 | DE |
| 19751761 | Oct 1998 | DE |
| 19725137 | Jan 1999 | DE |
| 19829224 | Jan 2000 | DE |
| 19909816 | May 2000 | DE |
| 10000937 | Aug 2001 | DE |
| 10136709 | Feb 2003 | DE |
| 10161160 | Jun 2003 | DE |
| 102005010010 | Sep 2005 | DE |
| 102004030836 | Jan 2006 | DE |
| 102005026251 | Jan 2006 | DE |
| 102005038394 | Mar 2006 | DE |
| 102005050286 | Apr 2006 | DE |
| 102004058122 | Jul 2006 | DE |
| 0501993 | Sep 1992 | EP |
| 0869745 | Oct 1998 | EP |
| 900048 | Mar 1999 | EP |
| 0928600 | Jul 1999 | EP |
| 977510 | Feb 2000 | EP |
| 1079240 | Feb 2001 | EP |
| 1152706 | Nov 2001 | EP |
| 1181897 | Feb 2002 | EP |
| 1319368 | Jun 2003 | EP |
| 1374792 | Jan 2004 | EP |
| 1374793 | Jan 2004 | EP |
| 1391181 | Feb 2004 | EP |
| 1421913 | May 2004 | EP |
| 1464285 | Oct 2004 | EP |
| 1504713 | Feb 2005 | EP |
| 1504726 | Feb 2005 | EP |
| 1519140 | Mar 2005 | EP |
| 1523951 | Apr 2005 | EP |
| 1561423 | Aug 2005 | EP |
| 1629774 | Mar 2006 | EP |
| 1629789 | Mar 2006 | EP |
| 2380550 | Oct 2011 | EP |
| 2876273 | Apr 2006 | FR |
| 2000023941 | Jan 2000 | JP |
| WO9424933 | Nov 1994 | WO |
| WO9501757 | Jan 1995 | WO |
| WO9608209 | Mar 1996 | WO |
| WO9610949 | Apr 1996 | WO |
| WO9626672 | Sep 1996 | WO |
| WO9729699 | Aug 1997 | WO |
| WO9729709 | Aug 1997 | WO |
| WO9836684 | Aug 1998 | WO |
| WO9916352 | Apr 1999 | WO |
| WO9927839 | Jun 1999 | WO |
| WO9943253 | Sep 1999 | WO |
| WO0016684 | Mar 2000 | WO |
| WO0028911 | May 2000 | WO |
| WO0047103 | Aug 2000 | WO |
| WO0049958 | Aug 2000 | WO |
| WO0057767 | Oct 2000 | WO |
| WO0069335 | Nov 2000 | WO |
| WO0101845 | Jan 2001 | WO |
| WO0137748 | May 2001 | WO |
| WO0162134 | Aug 2001 | WO |
| WO0164124 | Sep 2001 | WO |
| WO0176496 | Oct 2001 | WO |
| WO0176497 | Oct 2001 | WO |
| WO0187136 | Nov 2001 | WO |
| WO0193745 | Dec 2001 | WO |
| WO0200093 | Jan 2002 | WO |
| WO0200103 | Jan 2002 | WO |
| WO0219936 | Mar 2002 | WO |
| WO0222015 | Mar 2002 | WO |
| WO0224051 | Mar 2002 | WO |
| WO02056770 | Jul 2002 | WO |
| WO02064011 | Aug 2002 | WO |
| WO02082375 | Oct 2002 | WO |
| WO02098273 | Dec 2002 | WO |
| WO2004046754 | Jun 2004 | WO |
| WO2004060157 | Jul 2004 | WO |
| WO2004062497 | Jul 2004 | WO |
| WO2005016166 | Feb 2005 | WO |
| WO2005070318 | Aug 2005 | WO |
| WO200507293 | Oct 2005 | WO |
| WO2005101277 | Oct 2005 | WO |
| WO2005111942 | Nov 2005 | WO |
| WO2006002396 | Jan 2006 | WO |
| WO2006005021 | Jan 2006 | WO |
| WO06027781 | Mar 2006 | WO |
| WO06039009 | Apr 2006 | WO |
| WO2006039009 | Apr 2006 | WO |
| WO06051523 | May 2006 | WO |
| WO2006051523 | May 2006 | WO |
| WO2006090141 | Aug 2006 | WO |
| WO2007002079 | Jan 2007 | WO |
| WO2007031314 | Mar 2007 | WO |
| WO2007033206 | Mar 2007 | WO |
| WO2007062051 | May 2007 | WO |
| WO2007084893 | Jul 2007 | WO |
| WO2009158578 | Dec 2009 | WO |
| WO2010014538 | Feb 2010 | WO |
| WO2011145533 | Nov 2011 | WO |
| WO2012015801 | Feb 2012 | WO |
| WO2012024686 | Feb 2012 | WO |
| Entry |
|---|
| Malchano et al, 2006, “Integration of Cardiac CT/MR Imaging with Three-Dimensional Electroanatomical Mapping to Guide Catheter Manipulation in the Left Atrium: Implications for Catheter Ablation of Atrial Fibrillation” (pp. 1221-1229) (Year: 2006). |
| Nov. 29, 2017 USPTO Office Action (U.S. Appl. No. 13/773,981). |
| Medical Industry Today, “New Navigational Aid Could Improve Hip Replacement Outcomes,” Jul. 22, 1997. |
| European Patent Office, Extended Search Report issued for EP 11818898.6, 6 pages dated Dec. 20, 2013. |
| Patent Cooperation Treaty, International Search Report and Written Opinion from PCT/US06/35548, dated Aug. 20, 2007, 7 pages. |
| Highlights from Presentation of 5th Joint Meeting of European Assn. for Cardio-Thoracic Surgery and European Society of Thoracic Surgeons “Evidence for Fleece-Bound Sealants in Cardiothoracic Surgery” Sep. 9-13, 2006 Sep. 9, 2006. |
| Moore, E. et al., Needle Aspiration Lung Biopsy: Re-evaluation of the blood patch technique in an equine model, Radiology, 196(1) Jul. 1, 1995. |
| FDA Approves Lung Sealant, May 31, 2000 [online], [retried Oct. 17, 2008 from Internet]; http://www.meds.com/archive/mol-cancer/2000/05/msg01329.html Aug. 31, 2000. |
| Patent Cooperation Treaty, International Search Report from PCT/US11/48669, dated Apr. 9, 2012, 7 pages. |
| Jun. 15, 2018 USPTO Office Action (U.S. Appl. No. 13/773,990). |
| Jun. 14, 2018 USPTO Office Action (U.S. Appl. No. 15/287,648). |
| Sep. 9, 2016 USPTO Office Action (U.S. Appl. No. 13/773,981). |
| Dec. 4, 2015 USPTO Office Action (U.S. Appl. No. 13/773,981). |
| May 17, 2017 USPTO Office Action (U.S. Appl. No. 13/773,981). |
| Aug. 4, 2014 USPTO Office Action (U.S. Appl. No. 13/773,990). |
| Jul. 7, 2015 USPTO Office Action (U.S. Appl. No. 13/773,990). |
| Jun. 29, 2016 USPTO Office Action (U.S. Appl. No. 13/773,990). |
| Jun. 10, 2015 USPTO Office Action (U.S. Appl. No. 13/773,997). |
| Feb. 11, 2016 USPTO Office Action (U.S. Appl. No. 13/773,997). |
| Apr. 30, 2019 USPTO Office Action (U.S. Appl. No. 13/773,990). |
| Sep. 3, 2020 USPTO Office Action (U.S. Appl. No. 16/194,782). |
| Aug. 11, 2021 USPTO Office Action (U.S. Appl. No. 16/362,766). |
| Jan. 6, 2022 USPTO Office Action (U.S. Appl. No. 16/362,766). |
| Jun. 27, 2022 International Office Action (Serial No. 22164191.3). |
| Dec. 6, 2023 International Office Action (Serial No. 13751618.3). |
| Gottumukkala S. Raju, “Endoscope Technology Theory—Lesson 3—Endoscope Parts,” Nov. 26, 2020. |
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| 61602007 | Feb 2012 | US |
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