Exemplary methods, devices, systems, etc., presented herein generally relate to sensing gastric contractions.
The digestive system plays a role in a variety of endocrine disorders and metabolic disorders (e.g., anorexia, obesity, gastroparesis, diabetes, etc.). As these disorders involve complex mechanisms, medicine often uses an interdisciplinary approach. For example, a patient with anorexia may be treated by a psychiatrist and an endocrinologist and a patient with morbid obesity may be treated by a surgeon (e.g., Roux-en-Y gastric bypass). Over the past 20 years, gastric electrical stimulation or gastric pacing has emerged as another option to treat obesity.
With respect to obesity, the number of patients undergoing bariatric surgery for the treatment of obesity, and the proportion of the health care budget dedicated to this health problem, is growing exponentially. Yet some believe that, as a public health measure, bariatric surgery in the United States is being pursued in a less than optimal manner. This belief supports further testing of more controllable treatment options that rely on implantable programmable electronic stimulation devices. In particular, implantable devices that deliver gastric electrical stimulation have been effective in normalizing gastric dysrhythmia, accelerating gastric emptying and improving nausea and vomiting.
Gastric electrical stimulation (GES) therapies generally aim to control gastrointestinal motility. For example, GES using short duration pulses can reduce nausea and vomiting in patients with gastroparesis and GES using longer duration pulses can pace intrinsic gastric slow waves and thus normalize gastric dysrhythmia. Electrical stimulation of the small intestine, colon, or anal sphincter has also been reported for the treatment of dumping syndrome, constipation, and fecal incontinency.
For treatment of obesity, a therapy known as reverse (or retrograde) gastric pacing (RGP) can impair intrinsic gastric myoelectrical activity and substantially and acutely reduce food intake. RGP with a tachygastrial frequency of 9 cycles/min delivered using a pair of submucosal gastric electrodes implanted 5 cm above the pylorus in human subjects resulted in a reduction in the consumption of water, a reduction in food intake and an increase in gastric retention of a solid meal. Reduced food intake and freedom from symptoms resulting from moderate gastric stimulation are indicative of the therapeutic potential of RGP in treating obesity.
A particular form of gastric electrical stimulation is sometimes referred to as tachygastrial electrical stimulation (TES) where tachygastrial frequencies induce tachygastria and reduce normal slow waves. TES delivered at the distal antrum can reduce food intake, in a manner likely attributed to TES-induced reduction in proximal gastric tone, gastric accommodation, antral contractility and gastric emptying.
As various disorders and therapies pertain to gastric motility and, more specifically, waves or contractions of the gastrointestinal tract, techniques to monitor GI physiology are useful. Various techniques are discussed herein for monitoring GI contractions as well as other GI physiology.
An exemplary implantable device includes an emitter to emit radiation to illuminate a portion of the stomach and a detector to detect emitted radiation reflected by the portion of the stomach where a contraction of the stomach alters the reflected radiation. For example, during contraction, blood is excluded from the contracting region of the stomach and the stomach becomes less red in color. An exemplary method includes illuminating a portion of the gastrointestinal tract, detecting a change in illumination received by a detector where the change in illumination is responsive to a contraction of the gastrointestinal tract. Various other methods, devices, systems, etc., are also disclosed.
Features and advantages of the described implementations can be more readily understood by reference to the following description taken in conjunction with the accompanying drawings.
The following description includes the best mode presently contemplated for practicing the described implementations. This description is not to be taken in a limiting sense, but rather is made merely for the purpose of describing the general principles of the implementations. The scope of the described implementations should be ascertained with reference to the issued claims.
Various exemplary devices, methods, systems, etc., described herein relate to measurement of gastrointestinal contractions and optionally one or more other gastrointestinal physiologic measures. A particular device includes an emitter to emit radiation and a detector to detect emitted radiation as reflected or transmitted by the gastrointestinal tract. Such a device can output a signal that varies as the gastrointestinal tract contracts and relaxes. The signal can be used for any of a variety of purposes. For example, the signal can provide feedback to a stimulation device, the signal can determine digestive phase (fasting, cephalic, gastric, intestinal, etc.), or the signal can trigger any of a variety of actions (e.g., patient alert, information transmission, etc.).
Digestive phases are discussed below followed by a description of some gastrointestinal physiologic measures. Exemplary devices, systems and methods are described that can acquire one or more gastrointestinal physiologic measures, which, in turn, may be used for any of a variety of purposes.
More specifically, the cephalic phase 110 involves seeing, smelling and anticipating food and the brain informing the stomach that it should prepare for receipt of a meal. Communication is composed of parasympathetic stimuli transmitted through the vagus nerve to the enteric nervous system, resulting in release of acetylcholine in the vicinity of G cells and parietal cells. Binding of acetylcholine to its receptor on G cells induces secretion of the hormone gastrin, which, in concert with acetylcholine and histamine, stimulates parietal cells to secrete small amounts of acid. Additionally, a low level of gastric motility is induced. In essence, the gastric motor is turned on and begins to idle.
In the gastric phase 120, when a meal enters the stomach several additional factors come into play, foremost among them distension and mucosal irritation. Distension excites stretch receptors and irritation activates chemoreceptors in the mucosa. These events are sensed by enteric neurons, which secrete additional acetylcholine, further stimulating both G cells and parietal cells; gastrin from the G cells feeds back to the parietal cells, stimulating it even further. Additionally, activation of the enteric nervous system and release of gastrin cause vigorous smooth muscle contractions. The net result is that secretory and motor functions of the stomach are fully turned on—lots of acid and pepsinogen are secreted, pepsinogen is converted into pepsin and vigorous grinding and mixing contractions take place. However, there is a mechanism in place in the stomach to prevent excessive acid secretion: if lumenal pH drops low enough (less than about 2), motility and secretion are temporarily suspended.
In the intestinal phase 130, as food is liquefied in the stomach, it is emptied into the small intestine. It seems to be important for the small intestine to be able to slow down gastric emptying, probably to allow it time to neutralize the acid and efficiently absorb incoming nutrients. Hence, this phase of gastric function is dominated by the small intestine sending inhibitory signals to the stomach to slow secretion and motility. Two types of signals are used: nervous and endocrine. Distension of the small intestine, as well as chemical and osmotic irritation of the mucosa is transduced into gastric-inhibitory impulses in the enteric nervous system—this nervous pathway is called the enterogastric reflex. Secondly, enteric hormones such as cholecystokinin and secretin are released from cells in the small intestine and contribute to suppression of gastric activity.
Collectively, enteric hormones and the enterogastric reflex put a strong brake on gastric secretion and motility. As the ingesta in the small intestine is processed, these stimuli diminish, the damper on the stomach is released, and its secretory and motor activities resume.
It may be appreciated that the above mentioned digestive phases 100 include many sub-mechanisms. For example, mastication, saliva excretion, deglutition (swallowing), etc., are all part of the digestive process. Any of a variety of such mechanisms can trigger or condition gastrointestinal activity, which may alter gastrointestinal physiology.
As indicated by blood flow 210 and VO2(GI) 220, the cardiovascular system responds to feeding. During the cephalic phase 110 and the initial ingestion of food, a transient increase in cardiac output, aortic blood pressure and heart rate occur, which may be accompanied by an increase in mesenteric vascular resistance. Within about 5 minutes to 30 minutes after feeding, cardiac output, heart rate and blood pressure return to normal while blood flow through the superior mesenteric artery begins to rise and continues to do so for about 30 minutes to about 90 min. These responses can be attenuated by administration of sympathetic blocking agents. Thus, as in the case of early postprandial thermogenesis, the secretion of catecholamines may play an important role in the cardiovascular changes that occur during this ingestion phase.
Alterations in blood flow 210 to the absorptive site concomitant with changes in gut motility (e.g., contractions 230) can influence the net absorption of nutrients such as amino acids and electrolytes. A positive correlation exists between blood flow 210 and the absorption of passively and actively transported substances. Increased blood flow 210 can increase absorption by increasing O2 220 delivery to the mucosa, altering tissue colloid osmotic pressure or increasing the removal of an absorbed nutrient, thus increasing the concentration gradient between the lumen and the blood. For example, absorption of amino acids from the jejunum was found to be directly proportional to blood flow 210 and inversely proportional to gut motility (e.g., contractions 230).
With respect to contractions 230, the gastrointestinal tract is highly vascularized. Oxygenated blood is red; thus, in a relaxed state, the gastrointestinal tract appears red. However, when a contraction occurs, blood is forced from the constricted region of the gastrointestinal tract and it appears white (i.e., less red) compared to relaxed portions. Such a change has an analogy in the term “white knuckles” where a driver may grip a steering wheel in a manner that constricts blood flow to the tissue around the knuckles of the hand. For the stomach, a contraction may travel as a band having a width of about a centimeter or two. Hence, a change in color occurs in association with the contraction. As described herein, various techniques measure this color change.
In
The sensor for VO2 measurement 320 includes a lead body 321, sensor circuitry 322 and a window 324 that allows emitted radiation to interact with the surrounding environment and for reflected radiation to be detected. The particular example of
The sensor for VO2 320 can include a beam combiner subassembly built into the sensor assembly where the sensor 322, in turn, is built into an implantable lead 321. The sensor circuitry 322 includes a photo detector and an optional application specific integrated circuit (ASIC). The lead 321 includes a compartment with a pair of end caps that can be used to hermetically seal the sensor circuitry 322. The lead 321 tube can be made of an opaque material, such as metal (e.g., titanium or stainless steel) or ceramic, so long as it includes a window 324 to allow for interaction with the surrounding environment. The window 324 can, for example, be made of synthetic sapphire or some other appropriate material. Exemplary synthetic sapphires are marketed by Imetra, Inc. (Elmsford, N.Y.) and Swiss Jewel (Philadelphia, Pa.).
The optional ASIC, which can include filters, analog-to-digital circuitry, multiplexing circuitry, and the like, controls the emitters and processes photo detector signals produced by a photo detector in any manner well known in the art. As described herein, an ASIC may provide signals indicative of the photo detector signals to an implantable device, such as an implantable monitor, pacemaker, ICD, and/or metabolic therapy device (e.g., to treat obesity, diabetes, etc.). If an ASIC or equivalent circuitry is not included within the sensor circuitry 322, and the sensor circuitry 322 outputs analog signals, such signals can be delivered between the sensor circuitry 322 and the implantable device.
In the sensor circuitry 322, an opaque optical wall is positioned between the beam combiner subassembly and the photo detector. The various components can be attached to a substrate (e.g., by epoxy) where the substrate can be a printed circuit board (PCB). Bond wires can be used to attach the various components to the substrate, as well as to attach the substrate to terminals which extend through an insulated feedthrough in an end cap of the sensor compartment.
With respect to a lead-based sensor, the size of the beam combiner is preferably about 2 millimeters (mm) or less, and the size of the sensor circuitry 322 is about 4 mm or less, and preferably about 3 mm. The length of the sensor circuitry 322, which extends axially in the lead 321 can be somewhat larger, because the length of the lead 321 is relatively large as compared to the diameter of the lead.
The lead 321 may have a transparent housing, or include its own window, opening, or the like. The lead 321 can include tines for attaching the lead 321 to a desired position; the lead 321 may include any of a variety of types of fixation means, or none at all. Additionally, the lead 321 may also include a lumen for a stylet, which can be used for guiding the lead to its desired position.
The sensor 320 can include wires that provide power and possibly control signals to the sensor circuitry 322 from an implantable device, and provide pulse oximetry signals from the sensor circuitry 322 to the implantable device.
As described herein, a lead may include one or more electrodes configured for delivery of energy. For example, the lead 321 may include a ring electrode and a tip electrode that are connected to an implantable device by way of wires.
The sensor for contractions 330 includes various features of the sensor for VO2 320. For example, the sensor 330 includes a lead 331, sensor circuitry 332 and a window 334. In the example of
The exemplary circuit 340 includes various features of the TRS series reflective color sensors marketed by TAOS (Texas, USA). The TRS series devices are configured to convert reflected light intensity to an output voltage that is directly proportional to the reflected light intensity on the photodiode. The devices include an integral color LED and a matching color filters on the photodiode. Various components of the TRS series device are configured as a monolithic silicon IC (e.g., photodiode, operational amplifier and feedback components). Colors include red (630 nm), green (567 nm) and blue (470 nm). The TRS series devices can be configured to be triggered such that the emitter emits radiation only when desired. Thus, an exemplary circuit may be pulsed at particular times or in response to certain events to measure reflected radiation, for example, to measure contractions of the gastrointestinal tract.
The circuit 340 includes a housing or package 342 that houses an emitter 344 and a detector 346. The housing 342 includes connection tabs ground 342, anode 343, supply voltage 345 and output voltage 347 for the internal circuitry, as indicated in the circuit diagram. The output voltage 347 corresponds to intensity versus time. Thus, for a sensor mounted adjacent the stomach, a contraction will cause the intensity to increase as the stomach turns from red to white.
Exemplary sensor locations, labeled A to F, include A (the esophagus 422), B (the fundus 424), C (the pylorus 426), D (the distal antrum), E (the duodenum 428) and F (the ileum 434/the cecum 436). As these portions of the gastrointestinal tract include muscles that can contract, a sensor may be positioned at one of these positions to measure contractions. For example, a sensor may be positioned to measure contractions of a particular portion of the gastrointestinal tract (e.g., a portion of the stomach). Where such a sensor further includes circuitry to measure VO2, then contractions and VO2 may be measured.
As already mentioned, a sensor may provide a measure or signal to an implantable device. In various examples, such an implantable device is configured to deliver GES. As an implantable device may be alternatively or additionally configured for autonomic nerve stimulation, a brief description of the vagus with respect to the digestive system follows. The vagus enters the abdomen with two trunks (the right, dorsal or posterior and the left, ventral or anterior) that track generally along the esophagus. When the vagi cross the diaphragm, in most individuals they divide into five distinctive branches: (i-ii) paired gastric branches (e.g., associated with the stomach and the proximal duodenum), (iii-iv) paired celiac branches (e.g., associated with duodenum, jejunum, ileum, cecum and colon) and (v) a single hepatic branch that originates from the ventral trunk (e.g., associated with distal antrum, duodenum, liver and gall bladder). With respect to the diagram 400 of
The various locations labeled A-F provide general guidance for sensor placement. With respect to specific guidance,
Mucosa 525, which is the innermost layer (closest to the lumen 515) often described as the soft, squishy lining of the tract, consisting of epithelium, lamina propria and muscularis mucosae;
Muscularis circular 535, which is an inner circular layer of smooth muscle fibers wrapped around the long axis of the tract;
Muscularis longitudinal 545, which is an outer longitudinal layer of smooth muscle fibers extending parallel to the long axis of the tract; and
Adventitia/serosa 555, which is the outermost layer, which is called either adventitia (in regions where the tube passes through the body wall) or serosa (in regions where the tube passes through body cavities).
The muscularis of the stomach is often thicker than that elsewhere and the muscle fibers can be layered in more orientations (often described as assuming three layers, which are not readily distinguishable in routine sections). In the stomach, the inner layer of the muscularis forms a sphincter in the pyloric stomach (the pyloric sphincter).
Muscle contractions propel matter along the gastrointestinal tract. Muscle contractions of the gastrointestinal tract can be isolated to a single muscle layer or they may occur for multiple layers in a coordinated or uncoordinated manner. Contractions for multiple layers may occur in phase or out of phase. Phase locking may occur and contractions may be sequential, for example, where circular muscle contracts followed by longitudinal muscle. Contractions for multiple layers may be synchronous or asynchronous.
A study by Sarna (“Gastrointestinal longitudinal muscle contractions”, Am J Physiol Gastrointest Liver Physiol 265; G156-164, 1993) reported for a canine model, that, in the stomach, the longitudinal muscle contracted in a 1:1 relationship with the circular muscle contractions. Sarna noted that there was no significant difference between the frequency, duration and time of onset of gastric longitudinal and circular muscle contractions and their amplitudes were significantly correlated with each other. Sarna further noted that, in the small intestine when the circular muscle contracted, the longitudinal muscle exhibited passive elongation during the fasting and the fed state without any significant difference between the onset, duration and frequency of small intestinal circular muscle contractions and the passive longitudinal muscle elongations.
As described herein, an exemplary sensor can detect muscle contractions of the gastrointestinal tract and such contractions may indicate patient state or digestive phase (e.g., fasting state, fed state, cephalic phase, gastric phase, intestinal phase, etc.) and optionally degree of lumen occlusion.
As explained, multiple sensors may be implanted into the body to measure gastrointestinal contractions. As indicated in a plot 610 of intensity versus time, the axial locations A, A′ and A″ can allow for detection of contraction direction and optionally degree of luminal occlusion. Specifically, axial placement can record time of maximum intensity (i.e., contraction) and a stronger contraction can be more white (i.e., less red) and thereby cause a larger increase in intensity (i.e., amplitude) versus a weaker contraction.
Depending on features of the sensor, the implantable device 701 may acquire blood flow information 210, VO2 information 220 and/or contraction information 230. A signal 240 represents a digital signal generated in response to contractions (noting that an analog signal may be used or an analog signal may be converted to a digital signal). In the example of
The exemplary device 701 includes a programmable microprocessor 710 that can implement control logic 730 and other instructional modules 734. Information may be stored in memory 724 and accessed by the programmable microprocessor 710. For delivery of energy, the device 701 includes one or more pulse generators 742, 744. The pulse generators 742, 744 may rely on a switch 720 for delivery of energy via one or more connectors 725. While a device may include one or more integral leads, in general, a device includes one or more connectors for connecting a lead or leads to the device. More particularly, the connectors 725 provide for electrically connecting one or more electrodes and/or one or more sensors to the circuitry of the device 701. In the example of
The device 701 further includes one or more analog to digital converters 752, 754 for converting analog signals to digital signals or values. An exemplary sensor may provide a digital signal (e.g., high voltage as “1” and low voltage as “0”), for example, that corresponds to a contracted state and a relaxed state, respectively, of a portion of the gastrointestinal tract. The processor 710 may use a signal provided by one of the A/D converters 752, 754 to control a therapy or other process. A control signal from the processor 710 may instruct the switch 720 to select a particular electrode configuration for sensing electrical or other activity.
The device 701 may include one or more physiological sensors 760. Such sensors may be housed within a case of the device 701 (e.g., a motion sensor), include a surface mounted component, include a lead, include a remote sensor, etc. A sensor may provide a digital signal or an analog signal for use by the processor 710 or other circuitry of the device 701. A physiological sensor may provide a signal via one or more of the connectors 725 or it may be otherwise connected to device circuitry.
For purposes of communication with external or other implantable devices, the device 701 includes a telemetry circuit 770. The telemetry circuit 770 may include one or more antennae for transmission and/or receipt of electromagnetic signals. Such a circuit may operate according to a specialized frequency or frequencies designated for medical devices. Various conventional implantable devices rely on an associated programmer, which is typically an external computing device with a communication circuit suitable for communicating with an implantable device for purposes of data transfer, status checks, software download, etc. Where the circuit 770 communicates with an implantable device or a device in electrical connection with a patient's body, then the body may be a conductive medium for transfer of information. For example, the circuit 770 may be capable of communication with a specialized wristwatch where the body is relied upon as a conductor.
The device 701 further includes an impedance measuring circuit 774. Such a circuit may rely on instructions from the processor 710. For example, the processor 710 may instruct the circuit 774 to provide a measured impedance for a particular electrode configuration. In such an example, the processor 710 may also instruct the switch 720 to provide the circuit 774 with a particular electrode configuration. Impedance information may be used by the processor 710 for any of a variety of purposes (e.g., hardware condition, cardiac condition, edema, respiration, gastrointestinal, etc.). The processor 710 may store impedance or other information to memory 724 for later use or for transmission via the telemetry circuit 770.
The device 701 includes a power source, which is shown as a battery 780 in the example of
In
While the device 701 includes particular features, various exemplary devices, systems, methods, etc., may use or be implemented using a different device with more or less features.
The method 1050 may be performed on a scheduled basis or in response to a condition such as the “no” branch of the decision block 1016 of the method 1000. The method 1050 commences in a call block 1054 that calls for capture assessment. In the example of
Referring again to the decision block 1062, if this block decides that capture occurred, then the method 1050 continues at another decision block 1066 that decides if optimization should occur to optimize delivery of energy (e.g., to conserve energy, to minimize adverse tissue response, etc.). If the decision block 1066 decides that optimization is not required (e.g., already at a minimum level of energy delivery, optimization occurred within the last X hours, etc.), then the method 1050 enters a return block 1070 to exit the capture assessment. However, if the decision block 1066 decides that optimization should occur, the method 1050 enters the adjustment block 1064, as already explained with respect to the “no” branch for the capture decision block 1062.
Information may be recorded for any of the exemplary methods described herein. For example, for the method 1050, information about capture, parameter values, optimization, etc., may be recorded. Recorded information may be examined by a clinician to assess patient health, operation of an implantable device, etc.
In the example of
An exemplary method may detect one or more contractions and, in response, call for a particular action. For example, certain contractions may indicate that a bowel movement is imminent (e.g., to occur within a few minutes). A sensor may sense such contractions and alert a patient. In the system of
Although exemplary mechanisms (e.g., implemented as or in methods, devices, systems, software, etc.) have been described in language specific to structural features and/or methodological acts, it is to be understood that the subject matter defined in the appended claims is not necessarily limited to the specific features or acts described.