DETECTION AND LOCALIZATION

RELATED APPLICATIONS

The present application claims priority from US Provisional application number 63/350,427 filed on June 9, 2022, the disclosure of which is incorporated herein by reference.

FIELD OF THE INVENTION

The present disclosure relates generally to a system and method, which utilizes a nuclear radiation-based capsule designed to detect and localize bleeding within the gastrointestinal (GI) tract.

BACKGROUND OF THE INVENTION

X-ray based imaging capsules are used to perform CRC screening to detect polyps, lesions, and cancer in the colon, as described for example in US patent 9,844,354. An Xray based imaging capsule emits nuclear’ radiation and detects particles from Xray fluorescence and Compton backscattering in response to the emitted radiation. The imaging capsule detects changes in morphology of the colon by measuring the distances from the capsule to the colon wall and reconstructing 2D and 3D maps of the colon walls. Typically, the imaging capsule may use a tracking system such as described in US patent application publication 2014/0031642 and US patent application publication 2016/0066813 to follow the position of the imaging capsule as it traverses the gastrointestinal tract of the user.

A different problem that occurs in the GI tract is bleeding. GI track bleeding is a common occurrence in patients and is more frequent in elderly patients due to various causes, such as chronic use of Non-Steroid Anti-Inflammatory Drugs (NSAID), chronic use of anti-coagulation drugs, ulcers in the esophagus and stomach, bleeding in the small bowel, bleeding in the colon from a diverticulum, bleeding from colon polyps, colon Neoplasm (Malignant or benign) and other causes. Using an optical imaging capsule to detect bleeding is problematic, since the content of GI tract may block visible detection and the blood is not stationary, but rather flows with the content of the GI tract. Thus, other methods are needed to reliably detect bleeding in the GI tract.

SUMMARY OF THE INVENTION

An aspect of an embodiment of the invention, relates to a capsule for the detection and localization of GI track bleeding by detecting nuclear emission from radioisotopes injected into the blood. The capsule is configured to detect Beta radiation, Xray radiation and/or Gamma radiation through the whole GI track. The capsule is configured to identify its location with the help of internal sensors or is configured to collaborate with an external tracking system to track its location, for example utilizing an electromagnetic tracking system and two-way RF communications between the capsule and the tracking system.

There is thus provided according to an embodiment of the disclosure, a system for detecting blood in a gastrointestinal tract of a user, comprising:

A capsule that is configured to be swallowed by the user and traverse the gastrointestinal tract of the user;

A receiver that is configured to be positioned on the user to communicate with the capsule;

Wherein the capsule comprises: a) One or more detectors configured to detect nuclear radiation from radioisotope labeled blood; b) A capsule transceiver configured to communicate with the receiver;

Wherein the receiver comprises:

A receiver transceiver configured to communicate with the capsule transceiver;

Wherein the one or more detectors are configured to form counts of particles of specific energy levels corresponding to radiation emitted by the radioisotope labeled blood and transmit the counts to the receiver;

Wherein the system is configured to analyze the counts and detect bleeding within the gastrointestinal tract.

In an embodiment of the disclosure, the receiver comprises a tracking system configured to track the motion of the capsule. Optionally, the capsule includes sensors configured to identify entry into a specific organ along the gastrointestinal tract and estimate the location within the organ. In an embodiment of the disclosure, the one or more detectors are configured to detect radiation from labeled red blood cells. Alternatively or additionally, the one or more detectors are configured to detect radiation from labeled white blood cells. Alternatively or additionally, the one or more detectors are configured to detect radiation from labeled platelets. In an embodiment of the disclosure, the system is configured to detect and differentiate between bleeding and inflammations based on red blood cells and white blood cells labeled with different radioisotopes. Optionally, the detection of bleeding is affected by an identification of the location of the capsule. In an embodiment of the disclosure, the detection of bleeding is affected by fluctuations in the counts. Optionally, the system is configured to identify the direction and distance to a bleeding location based on the difference in counts between different detectors and the energy levels measured by each detector.

There is further provided according to an embodiment of the disclosure, a method for detec ting blood in a gastrointestinal tract of a user, comprising:

Labeling blood of the user with a radioisotope;

Placing a receiver on the body of the user to communicate with the capsule;

Swallowing a capsule to traverse the gastrointestinal tract of the user; Forming counts of particles of specific energy levels corresponding to radiation emitted by the radioisotope labeled blood by one or more detectors in the capsule;

Transmitting the counts from the capsule to the receiver; and Analyzing the counts to detect bleeding within the gastrointestinal tract. BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be understood and better appreciated from the following detailed description taken in conjunction with the drawings. Identical structures, elements, or parts, which appear in more than one figure, are generally labeled with the same or similar number in all the figures in which they appear, wherein:

Fig. 1 is a schematic illustration of a system for detecting bleeding within the gastrointestinal tract, according to an embodiment of the disclosure;

Fig. 2 is a schematic illustration of an imaging capsule for detecting bleeding within the gastrointestinal tract, according to an embodiment of the disclosure; and

Fig. 3 is a flow diagram of a method of detecting bleeding within the gastrointestinal tract, according to an embodiment of the disclosure.

DETAILED DESCRIPTION

Fig. 1 is a schematic illustration of a system 100 for detecting bleeding within the gastiointestinal tract 199, and Fig. 2 is a schematic illustration of a capsule 150 within the gastrointestinal tract 199, according to an embodiment of the disclosure. The capsule 150 includes one or more detectors 170 configured to detect nuclear radiation emitted from blood cells (white and/or red) and determine if the bleeding 164 occurs within the vicinity of the capsule 150. In an embodiment of the disclosure, the system 100 includes a receiver 120 with a capsule tracking system 125 to enable identification of the location of the capsule 150 within the gastrointestinal tract 199. Optionally, the receiver 120 is worn by the user so that it is in the vicinity of the capsule 150 as it traverses the gastrointestinal tract 199. In an embodiment of the disclosure, the capsule 150 and the receiver 120 include a transceiver (125, 175 respectively) to communicate with each other and provide measurements from the detectors 170 and other sensors within the capsule 150 to the receiver 120 and instructions from the receiver 120 to the capsule 150. The receiver 120 may include a processor 124 and memory 126 to process the information provided by the capsule to determine if bleeding 164 is detected. In some embodiments of the disclosure, the receiver 120 processes the measurements from the detectors 170 and makes determinations in real-time. Alternatively or additionally, the capsule 150 may also process measurements and makes determinations.

In an embodiment of the disclosure, the receiver 120 analyzes information in real-time and may also record the information on a memory ⁷ card (e.g., SD card) for later analysis. Alternatively or additionally, the receiver 120 may transmit the information to an external computer 130 for analysis with an analysis program 145 executed on the computer 130. Computer 130 may receive the information in real-time or after the capsule exits the gastrointestinal tract 199 and ceases to communicate with the receiver 120. Optionally, computer 130 may prepare a report for a practitioner indicating if the capsule 150 detected bleeding 164 and the location of the bleeding. The report may include a graphical map 180 illustrating locations in which bleeding was detected. Optionally,, the capsule 150 may also include an imaging system 169 to provide images taken from within the gastrointestinal tract 199. The imaging system 169 may be based on using visible light or based on the use of nuclear radiation emitted from a radiation source in the capsule 150. In an embodiment of the disclosure, the computer 130 may display the graphical map 180 on a screen 135 and/or provide instructions in real time to the capsule 150, for example to take a picture.

In an embodiment of the disclosure, the determined locations mav be accurate, for example the exact position comprising coordinates relative to the tracking system 122 or may be approximate, for example identifying the organ in which the capsule 150 is located (e.g.. using the tracking system 122 or based on PH sensors, pressure sensors or other sensors in the capsule 150). Additionally, the capsule may estimate if it is near the entrance, middle or exit of the organ, or the capsule may identify entry into an organ and estimate tire advance of the capsule within the organ, for example based on a timer and/or motion sensors.

Fig. 3 is a flow diagram of a method 300 of detecting bleeding 164 within the gastrointestinal tract 199. according to an embodiment of the disclosure. Initially, a practitioner extracts (310) blood from the user and labels red blood cells, plasma and/or white blood cells with a radioisotope. The labeled blood cells are injected (320) into the user and within a few minutes they spread through the entire blood stream of the user, so that a small percent of the user’s blood is marked with the radioisotope.

In an embodiment of the disclosure, the user swallows (330) the capsule 150 through his or her mouth 190 to traverse the gastrointestinal (GI) tract 199. The capsule flows through the esophagus 191, stomach 192, small intestine (bowel) 193, the cecum 194, which is the beginning of the colon 195. Then the capsule 150 passes through the colon 195 and exits through the rectum and anus (not shown). Optionally, the tracking system 122 tracks (340) the flow of the capsule 150 through the gastrointestinal tract 199. In an embodiment of the disclosure, while flowing through the gastrointestinal tract 199 the detectors 170 in the capsule 150 are configured to measure (350) radiation by counting particles of specific preselected energy levels, to provide in real-time a count for each energy level at each detector 170. Optionally, the measurements are processed locally within the capsule 150 or transmitted to the external receiver 120 to be processed. The measurements are then analyzed (360) taking into consideration the location of the capsule 150 and the counts for each energy level at each detector 170. Based on the analysis the system 100 is able to detect (370) “hot-spots” with high levels of radiation of specific energies according to the radioisotope injected into the blood stream. The detected “hot-spots” provide an indication of locations with active bleeding 164 or hemostasis.

In an embodiment of the disclosure, red blood cells are radiolabeled with Tc99M, Cr51 P32, Hgl97, Hg203, Rb81 or Ini 11 (e.g., Ini 11 Oxine) using standard nuclear medicine (NM) red blood cell radiolabeling procedures. Tc99M is more adapt for upper GI track bleeding indication (Esophagus 191, Stomach 192. and Small Bowel 193) due to their relative short physical 1/2 life (6 hours). Thus the radiation might not be detectable by the time the capsule 150 reaches the colon 195. In i 11 with a physical 1/2 life of 2.8 Days is suitable for detection of upper GI bleeding as well as lower GI bleeding (colon and rectum). Cr51 can be used mainly as a Beta emitter (752 KeV) with 1/2 life of 27 Days.

In some embodiments of the disclosure, red blood cell (RBC) radiolabeling is performed by injecting a radioisotope linked with a molecule, which penetrates the RBC cell membrane. This procedure is somewhat less efficient in terms of percentage of labeled red blood cells, but it saves time. Radiolabeling is then performed in vivo, instead of extracting blood and labeling in vitro and then injecting back into the user. This also reduces the risk of mixing blood samples from different people, which can be fatal.

In an embodiment of the disclosure, the detectors 180 are adapted to detect Beta radiation, Xray and/or Gamma radiation. For example, the detectors 170 may be adapted to detect: a) Beta radiation in the range of about 448 KeV emitted by In 111 , about 752 KeV in the case of Cr51 and about 1710 Kev in the case of P32 radiolabeling. b) Gamma radiation with the energy of about 14'1 KeV (High energy) and 20-30 Kev (Low energy) for Tc99M radiolabeling and/or detection of about 170-245 KeV in the case of In i 11 la beling.

Other radioisotopes that may be used for labeling red blood cells may include 1123 and 1125. In an embodiment of the disclosure, each energy level (e.g., high, low levels for each possible radioisotope) is counted independently to estimate the distance from the emitting radioisotope. Optionally, the capsule comprises a controller 155 that controls the detectors 170. The controller 155 with the detectors 170 handle photocounting, energy discrimination and counting logic to separate different energies into different counts/bins.

In an embodiment of the disclosure, after injection (320) of labeled red blood cells, the user swallows (330) the capsule 150 with radiation detectors 170 suitable for the detection of Beta radiation, Xrays and/or Gamma radiation emitted by the respective radio isotope. Optionally, before swallowing the capsule the user drinks a cup or two of water so that the user’s stomach 192 is not empty and waits a few minutes for the radioisotope to circulate through the user’s bloodstream. Once the capsule is swallowed (330), it quickly arrives in the stomach 192, where it is expected to naturally stay for a few minutes to a few hours before it is moves to the small bowel 193. The capsule is swallowed (330) when it is fully operational, with the detectors 170 ready to detect and count radiation.

In the stomach 192, the capsule 150 measures the Beta electron counts and/or photon count rate with the detectors 170. If more than one energy level is available, such as in the case of lull 1, the different levels (e.g., a low level and a high level) are registered in separate counters/bins.

In an embodiment of the disclosure, multiple detectors 170 are used to identify the direction from the capsule 150 to the bleeding 164. Optionally, the detectors 170 are arranged along an inner contour of the capsule 150, for example near the inner surface of the capsule shell 185. Optionally, a set of 3-10 detectors are arranged symmetrically around the contour of the capsule shell 185 to enable identifying the direction to the bleeding 164. As an example, 6 detectors 170 may be arranged symmetrically to form a hexagon around the inner contour of the capsule shell 185.

In an embodiment of the disclosure, radiation is counted per detector 170 and per energy level. A count for each energy level may be stored in a separate bin. The radiation counts from all detectors and from all energy levels (e.g., high and low energy levels from a specific radioisotope) are analyzed to detect if there is a preferred side of the capsule that receives higher count rates in the high energy bins. If such a side of the capsule 150 is dominant, this means that the radiation is not near the capsule. Also, if the proportion of high and low radiation counts is not as expected from natural proportion of the radioisotope, this indicates that the source is far and some of the low energy radiation has been absorbed by the tissue separating the capsule from the radioisotope location. These indications signify that the measurements are based on radiation from distant organs with a lot of blood, for example, the liver or other organs that accumulate a lot of red blood cells.

In some embodiments of the disclosure. Beta radiation detectors are placed close to the capsule shell 185 or alternatively as part of the capsule shell 185 to optimally detect beta radiation since the maximal range of beta radiation is only a few millimeters in plastic or in the detectors 170. The detectors 170 may be made of Silicone, Silicone Carbide or plastic scintillators with light detection electronics attached for the detection of the Beta radiation from Ini 11, P32 or Cr51.

In an embodiment of the disclosure, detectors 170 are configured to detect low energy radiation from radioisotopes within the gastrointestinal tract 199, for example from lu l l 1 or Tc99M. The low energy radiation helps determine that the bleeding 164 or inflammation 166 is near the location of the capsule 150. The low energy radiation is too weak to penetrate the user’s body and be detected by external detectors. Therefore some radioisotopes and/or radiation levels can only be used for detection with a capsule 150 within the gastrointestinal tract 199 and not with external detectors (e.g., scintigraphy). As the capsule 150 travels in the small bowel 193 and colon 195, the capsule 150 detects radiation coming from the tissue nearby, since for example in the case of labeling with Ini 11, the Xray radiation is around 22 Kev which is strongly absorbed by tissue, most of the low energy counts are contributed from radioisotopes (e.g., from bleeding 164) near the capsule.

In an embodiment of the disclosure, when the count at differen t detec tors 170 around the capsule is more or less equal for low energies, it indicates that the contents of the stomach 192 , small bowel 193 or colon 195 (wherever the capsule is currently located) is mixed with radioisotope labeled red blood cells. Therefore bleeding 164 occurred in a preceding GI track section. This provides an indication to the presence of bleeding and its approximate location. In some embodiments of the disclosure, the capsule is continuously tracked by tracking system 122 that is worn by the user. Optionally, the location measurements provided by the hacking system 122 can be used for applying treatments with other means, such as colonoscopy, laparoscopic operations, gastroscopy (upper endoscopy).

In an embodiment of the disclosure, radiation "hot spots" can be characterized by a count rate. If the count late is above a preselected threshold value or there is a significant fluctuation in the radiation count, this provides an indication of the existence of bleeding 164 in the vicinity of the capsule 150. An example of such a "hot Spot" is a diverticulum 162, which may bleed in the colon 195 and cause substantial blood loss. As the capsule 150 moves along the colon 195, a bleeding diverticulum 162 can be detected as a pool of radiation close to the capsule 150, typically with detection preference to one side. An estimate of the distance from the capsule 150 to the bleeding 164 position and hence to the understanding that it is a diverticulum 162 can be reached by examining the count rate from the different detectors 170 and different energy bins (high and low energy bins separately) to estimate the direction of the radiation pool. Likewise comparing the ratio between the low energy count and the high energy count at the detectors 170 provides an indication of the distance to the bleeding, which forms a radiation pool. In some embodiment of tlie disclosure, capsule 150 is used as a fest line of investigation, which can save time and reduce the risk of bowel cleansing and performing invasive procedures on frail patients. Detecting bleeding 164 with the capsule 150 does not require extensive preparation compared to colonoscopy that requires bowel cleansing and is an invasive procedure with the risk of puncturing the user. When using a detection capsule 150, once red blood cells are extracted, labeled, and injected, the capsule can be swallowed to examine the entire gastrointestinal tract 199 for bleeding 164 from the stomach 192 to the end of the colon 195.

In an embodiment of the disclosure, blood platelets are labeled with radioisotopes, for example with Ini I I. Platelets serve a central role in hemostasis thus labeled platelets give rise to scintigraphic “hot spots” at bleeding sites in cases of intermittent gastrointestinal hemorrhage. As the capsule 150 passes in the gastrointestinal track 199, such "hot spots” can be detected by the capsule showing high local radiation activity specifically picked up by the capsule as it passes in the gastrointestinal track 199.

In an embodiment of the disclosure, white blood cells may be labeled with radioisotopes, for example Ini 11, Tc99M or other radiopharmaceuticals. As the capsule passes in the gastrointestinal track, it may detect regions of high radioactivity, specifically, detecting the low energy Xrays (20-30 KeV) and/or Beta radiation (448 KeV). Optionally, when the capsule 150 is near a site of accumulated white blood cells, which may indicate an area with an inflammation or infection 166 in the gastrointestinal track 199. Inflammation or infection "hot spots” may arise from ulcers, IBD, Chron’s disease, diverticulitis, and other types of inflammation or infections.

In an embodiment of the disclosure , the locations of bleeding 164 and/or inflammation/ infection 166 or other abnormalities are recorded by the receiver 120, for example based on the tracking system 122 and other sensors 174. Optionally, the recorded locations also record entrance into a specific organ, the distance traveled until reaching the bleeding 164 or inflanmiation/infectioii 166 within the organ and the distance until exiting the organ. In an embodiment of the disclosure, estimation of distance traveled in the small bowel 193 and the colon 195 is important io enable localization of the bleeding 164 or inflamniation/infection 166 to assist in intervention with a colonoscope in the colon 195, double balloon endoscope in the small bowel 193 and gastroscope in the esophagus 191 and the stomach 192. Optionally, to estimate the length traveled in the small bowel 193, the movements of the capsule 150 in the direction of its long axis are taken a s these movements have a high probability of being real movements along the small bowel 193. Additionally, these movements in the small bowel 193 are usually at relatively predicted time intervals and velocity, both of which can be deduced from the movement data along the capsule long axis. To estimate progress in the colon 195, the tracking system 122 is used and reference coordinates on the patient body are employed for estimation of the progress through the colon 195.

In an embodiment of the disclosure, red blood cells and white blood cells are labeled with different radioisotopes, for example Tc99m for red blood cells and Ini 11 for white blood cells. Both red and white blood cells are injected to the patient and the detectors are set to detect high energy gammas (141 KeV from Tc99m) and low energy ⁷ Xrays (20-30 KeV) and beta (484 KeV) from the InI 11. In this mode of operation, the capsule can separate between inflammation 166 and bleeding 164 and thus with this combined information, ulcers or diverticulum which are inflammatory, and bleeding 164 can be distinguished from noninflammatory ulcers or diverticulum 162. Optionally, differentiating between bleeding 164 and inflammation 166 assists in follow ⁷ -up imaging (e g., with an imaging capsule) after drug treatment to evaluate the effectiveness of the given drug treatment to the bleeding.

In an embodiment of the disclosure, the data accumulated in the receiver 120 is downloaded to computer 130 and processed to enable a practitioner to view a graphical map exemplifying the locations of scintigraphic hot-spots such as bleedin <g_ 164, ■ diverticulum 162, inflammations 166 and other abnormalities. Optionally, the practitioner may use this information to suggest follow up treatment.

In an embodiment of the disclosure,, after injecting labeled red blood cells (and or white blood cells), the user swallows the capsule after waiting a few minutes. Optionally, the user is further examined with a gamma camera to perform a quick overall scan. The quick overall scan can quickly detect severe hemorrhage without waiting for the capsule to reach the hemorrhage point. This method can save time in diagnosing a patient and can be confirmed when the capsule 150 passes nearby the hemorrhage.

The detection of bleeding in the GI track, especially when detected in the colon may be a clinical sign of advanced adenoma or colorectal cancer. As such, the bleeding detection capsule 150 may be used as a method for colorectal cancer screening, which detects bleeding 164 and which also gives an indication of the position in the colon 195 where bleeding occurs. Optionally, such a detection may indicate the existence of an advanced adenoma or colorectal cancer at that loca tion in the colon 195. Additionally, this method has the advantage of detecting bleeding 164 in the colon 195 even if the user has fistula or hemorrhoids which bleed almost always near the rectum 196 or the anal canal 197. These types of bleeding prevent the use of standard colorectal cancer screening stool based tests such as Fecal immunochemical test (FIT) or stool DNA + Fecal immunochemical test (FIT) as these tests will give false positive results for the user.

In some embodiments of the disclosure, the location of the capsule 150 is determined by the tracking system 122, for example using coils, magnetometers and magnetic fields as known in the art. Alternatively or additionally, the imaging capsule may use various sensors 174, for example an accelerometer, magnetometer, pressure sensor, timer/counter, PH sensor or other sensors to identify the location of the capsule 150. Optionally, the location may include identifying in which organ the capsule 150 is located and/or where the capsule 150 is located within the organ based on measurements performed by the various sensors 174 in the capsule 150. Optionally, analysis of the measurements from the detectors 170 may be affected by the identified loca tion of the capsule 150.

It shotild be appreciated that the above-described methods and apparatus may be varied in many ways, including omitting, or adding steps, changing the order of steps and the type of devices used. It should be appreciated that different features may be combined in different ways. In particular, not all the features shown above in a particular embodiment are necessary in every embodiment of the invention. Further combinations of the above features are also considered to be within the scope of some embodiments of the invention.

It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather the scope of the present invention is defined only by the claims, which follow.