WO2020031175A1

WO2020031175A1 - Device and method for in-vivo positioning

Info

Publication number: WO2020031175A1
Application number: PCT/IL2019/050873
Authority: WO
Inventors: Sharon BEN YEHUDA; Ram BEN YEHUDA
Original assignee: Photopill Medical Ltd.
Priority date: 2018-08-04
Filing date: 2019-08-01
Publication date: 2020-02-13

Abstract

An In-Vivo Object (IVO) location determination system, a method for providing treatment to a patient, and a device, the IVO location determination system comprising: an external device adapted to be positioned externally to a body of a patient, the external device comprising one or more acoustic waves transmitters; an IVO comprising one or more acoustic waves receivers; a controller for controlling the transmission of acoustic waves by the acoustic waves transmitters; and a processor configured to determine a location of the IVO relative to the external device, based on time differences between transmission times and receiving times of acoustic waves, wherein the acoustic waves transmitters and the acoustic waves receivers include four or more transducers comprising acoustic waves receivers or acoustic waves transmitters.

Description

DEVICE AND ME THOD FOR IN-VIVO POSI TIONING

TECHNICAL FIELD

The present disclosure relates to medical devices in general, and to a device and method for obtaining a location of an in-vivo device, in particular.

BACKGROUND OF THE INVENTION

In vivo devices are used in many bodily lumens, such as the arterial system, the digestive system or the respiratory system, and for a wide variety of medical applications. Such applications may include but are not limited to imaging purposes, endoscopic surgeries, heart catheterization, intestine diagnostic using capsules, and others. Many of these procedures need to be carried out at a specific location within the bodily lumen, and thus require the identification of the location of a device within the human body.

Current techniques require that the procedures are performed under an imaging device such as MRI or ultrasound, in order to obtain the location of the device. However, performing procedures under MRI or ultrasound requires highly trained healthcare professionals, as well as the use of equipment, which is expensive and in high demand, which increases the cost and limits the availability of the procedures. These inventions describe a system for computing the location of an in-vivo device and potentially taking an action (such as releasing medication or performing a medical procedure) . SUMMARY OF THE INVENTION

According to one aspect of the invention provided an in- vivo object (IVO) location determination system, comprising: an external device adapted to be positioned externally to a body of a patient, the external device comprising at least two acoustic waves transducers configured to transmit or receive an acoustic wave; an IVO comprising at least one acoustic waves transducer configured to receive or transmit an acoustic wave; a controller for controlling the transmission of acoustic waves; and, a processor configured to determine a location of the IVO relative to the external device . Within the system, the location is determined based on the time differences between transmission times and receiving times of the acoustic waves. Alternatively, the location is determined based on phase differences between the received acoustic signals . Within the system, at least two acoustic wave transducers of the external device are located on the same plane. Within the system, the external device is in a form of a flexible belt designed to be worn by the patient. Within the system, the external device is in a form of a flexible belt designed to be worn by the patient. Within the system, wherein the belt comprises at least three transducers configured to transmit and receive the acoustic wave. Within the system, the at least three transducers are arranged such that at least one pair of acoustic wave transducers has at least one common Cartesian coordinate . Within the system, the transducers are arranged such that at least one pair of acoustic wave transducers has at least one common Cartesian coordinate . Within the system, the first pair of transducers has at least one common Cartesian coordinate, and the second pair has at least two common Cartesian coordinates. Within the system the at least one transducer of the IVO receives acoustic waves transmitted by the at least two transducers of the external device, and responds by transmitting the corresponding acoustic signal to be received by the one or more acoustic waves transducers of the external device, and wherein the calculation of the position is performed on the external device. Within the system, the corresponding signal is transmitted immediately upon reception of the signal by the IVO. Alternatively, within the system, the corresponding signal is transmitted following a predetermined time interval upon the reception of the signal by the IVO. Alternatively, within the system, the at least one transducer of the IVO receives acoustic waves transmitted by the at least two transducers of the external device, and wherein the processor is located on the IVO. Within the system, the acoustic waves transmitted by the at least two acoustic waves transducers are transmitted in separate time slots. Within the system, the acoustic waves transmitted by the at least three acoustic waves transducers have different frequencies. Within the system, the processor is configured to determine an average of distances between the transducer of the IVO and each of the at least three transducers of the external device. Within the system, the system comprises least four transducers configured to receive the acoustic wave. Within the system, the first pair of the at least three transducers configured to receive the acoustic wave are on a first plane, and a second pair of the at least four transducers configured to receive the acoustic wave are on a second plane, and wherein the second plane perpendicular to the first plane. Within the system, the processor is further configured to determine a first angle between a line connecting the transducer of the IVO and the first plane, and a second angle between a second line connecting the transducer of the IVO and the second plane. Within the system, the at least one transducer of the IVO receives the acoustic waves transmitted by the at least one of the three transducers of the external device, and the location of the IVO is determined in accordance with the travel times between the at least one transducer of the IVO and each of the at least three transducers of the external device. Within the system, the calculation of the position is performed on the IVO. Alternatively, within the system, the processor is located externally to the IVO.

According to another aspect of the invention provided an IVO location determination system, comprising an external device configured to be positioned externally to a body of a patient, wherein the external device is designed as a belt to be worn by the patient, wherein the belt comprises a member designed to be placed over the navel of the patient, wherein the member comprises at least one transducer configured to transmit an acoustic wave and at least three transducers configured to receive an acoustic wave. Within the system, at least three transducers configured to receive an acoustic wave are located in the vicinity of the transducer configured to transmit an acoustic wave. Within the system, each of at least three transducers configured to receive an acoustic wave are further configured to operate as receivers of the acoustic wave. Within the system, the system comprises at least four transducers. Within the system, a first pair of the at least four transducers are on a first plane, and a second pair of the at least four transducers are on a second plane, and wherein the second plane is perpendicular to the first plane. According to yet another aspect of the invention, provided method of treating a patient in need comprising

a) receiving an indication to a location within a bodily lumen at which an treatment is to be performed;

b) providing a first IVO to be internalized by the patient, wherein the first IVO is configured to provide the treatment to the patient; c) determining the location of the IVO by the location determination system comprising:

an external device positioned externally to the body of the patient, wherein the external device comprises at least two acoustic waves transducers configured to transmit the acoustic wave; an IVO inserted into a bodily lumen of the patient, wherein the IVO comprises at least one transducer configured to receive the acoustic wave; a controller for controlling the transmission of acoustic waves by the at least one acoustic waves transducer of the external device; and a processor configured to determine the location of the IVO relative to the external device, based on time interval between transmission times and receiving times of the acoustic waves; and

e) Providing the treatment at the by the IVO at the location where treatment is needed.

Within the method, the treatment is selected from the group consisting of endoscopic surgeries, heart catheterization, applying Low Level Light Therapy by an intestine capsule, drug dispensing, and sample collection. Within the method, it further comprises the step of generating the mapping of the bodily lumen using a second IVO, such that each location within the bodily lumen is associated with at least one image. Within the method, the second IVO comprises an image acquisition unit, and wherein at least one image acquired by the image acquisition unit is associated with a location of the second IVO at the time of image acquisition. Within the method wherein the location of the second IVO is provided relatively to a bodily feature. Within the method, the IVO can be programmed to automatically initiate treatment or procedure when it reaches the pre-defined location.

According to yet another aspect of the invention, provided an IVO comprising: at least one acoustic waves transducer; a controller for controlling the transmission of acoustic waves by the at least one acoustic waves transducer; and a processor configured to determine a location of the IVO based on time interval between receiving times of acoustic waves by the at least one acoustic waves transducer, wherein the acoustic waves are transmitted by at least three acoustic waves transducers located on an external device configured to be positioned externally to the body of a patient.

According to further aspect of the invention, provided an IVO comprising: at least one acoustic waves transducer; a controller for controlling the transmission of acoustic waves by the at least one acoustic waves transducer; and a processor configured to determine a location of the IVO based on time interval between receiving times of acoustic waves by the at least one acoustic waves transducer, wherein the acoustic waves are transmitted by at least three acoustic waves transducers located on an external device configured to be positioned externally to the body of a patient for use as a therapeutic tool.

According to yet a further aspect of the invention, provided an IVO comprising: at least one acoustic waves transducer; a controller for controlling the transmission of acoustic waves by the at least one acoustic waves transducer; and a processor configured to determine a location of the IVO based on time interval between receiving times of acoustic waves by the at least one acoustic waves transducer, wherein the acoustic waves are transmitted by at least three acoustic waves transducers located on an external device configured to be positioned externally to the body of a patient for use as a diagnostic tool .

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosed subject matter will be understood and appreciated more fully from the following detailed description taken in conjunction with the drawings in which corresponding or like numerals or characters indicate corresponding or like components. Unless indicated otherwise, the drawings provide exemplary embodiments or aspects of the disclosure and do not limit the scope of the disclosure. In the drawings:

Fig. 1A is a schematic illustration of a patient wearing an exemplary external device, in accordance with some exemplary embodiments of the disclosed subject matter;

Fig. IB, 1C and ID are schematic illustrations of a top, front and back views of the exemplary external device, in accordance with some exemplary embodiments of the disclosed subject matter;

Figs. 2A and 2B are schematic illustrations of distances between transducers of the external device, in accordance with some exemplary embodiments of the disclosed subject matter;

Fig. 3 shows schematic graphs of acoustic wave transmitted, and the echo signals received, in accordance with some exemplary embodiments of the disclosed subject matter;

Fig. 4 shows a schematic circuit of an exemplary structure of acoustic waves transducer, in accordance with some exemplary embodiments of the disclosed subject matter;

Fig. 5 shows a schematic circuit of an exemplary structure of an IVO circuit implementing the "time-stamp" embodiment, in accordance with some exemplary embodiments of the disclosed subject matter;

Fig. 6 shows a schematic block diagram of an exemplary structure of an external device, in accordance with some exemplary embodiments of the disclosed subject matter;

Fig. 7 is a flowchart of steps in a method for determining the position of an IVO operating in accordance with the exemplary "time stamp" embodiment of the disclosed subject matter;

Fig. 8, showing an exemplary graph of transmitted and received signals in a system in accordance with the "transponder" embodiment

Fig. 9, illustrating an exemplary structure of the IVO circuit operating in accordance with the exemplary transponder embodiment of the disclosed subject matter;

Fig. 10A illustrates a patient wearing external device, in accordance with some exemplary embodiments of the disclosed subject matter;

Fig. 10B is a schematic illustration of a first embodiment of a member of an external device comprising transducers, in accordance with some exemplary embodiments of the disclosed subject matter;

Fig. 10C is a schematic illustration of a second embodiment of a member of an external device comprising transducers, in accordance with some exemplary embodiments of the disclosed subject matter;

Fig. 11 shows schematic graphs of acoustic wave transmitted, and the echo signals received from a system comprising the device of Figs. 10A and 10B, in accordance with some exemplary embodiments of the disclosed subject matter;

Fig. 12 shows a schematic illustration of angle measurement for a system comprising the device of Figs. 10A and 10B, in accordance with some exemplary embodiments of the disclosed subject matter; and

Fig. 13 is a flowchart of steps in a method for utilizing location information received from an IVO for carrying out localized treatment or procedure, in accordance with some exemplary embodiments of the disclosed subject matter.

DE TAILED DESCRIPTION OF THE INVENTION

One technical problem dealt with by the disclosed subject matter is the need to determine the location of an In-Vivo Object (IVO) within a body lumen. In some procedures, an IVO may be used at the preliminary stage for mapping the bodily lumen, and possibly identifying one or more specific locations, for example an area at which a treatment such as dispensing medication or any other chemical substance, or another procedure is to be applied. The location needs to be identified by coordinates relative to a known point which can be restored. Then, the IVO, or another IVO may be inserted, and its location may be tracked relative to the known point, until the device reaches the intended location. The treatment can be performed at that point or area. The initial mapping and the tracking therefore need to be aligned such that locations are measured relative to the same point. In other applications, the intended treatment location, or a map or another description of the lumen may be obtained from another source or by another technique, with or without the preliminary use of the IVO. Acoustic waves are advantageous in that they easily travel within soft human tissues and organs, and do not cause harm to the patient tissues .

The invention provides a 3D positioning system, that accurately and efficiently provides the location of an IVO. In one embodiment, the system comprises an external device configured to be located externally to the patient and in contact with the skin of the patient for best acoustic coupling. In one embodiment, the external device is in a direct contact with the skin of the patient. In one embodiment, the external device is in contact with the skin of the patient via a media suitable for transduction of acoustic waves. In one embodiment, the external device is in contact with the skin of the patient via acoustic coupling gel. In one embodiment, the external device is designed as a flexible belt to be worn by the patient. In another embodiment, the external device is a flexible patch designed to make a local contact with the skin of the patient.

In one embodiment, the external device comprises three or more transducers configured to transmit or receive an acoustic wave. In yet further embodiment, the IVO comprises one or more transducers configured to transmit or receive an acoustic wave. In yet another embodiment, the external device and the IVO comprise together at least four transducers configured to transmit or receive an acoustic wave.

In one embodiment, each transducer is configured to transmit and/or receive acoustic waves. In yet further embodiment, each transducer comprises a piezo-electric transducer that is being used by medical ultrasound systems or similar. The non-limiting example of transducer that is being used by medical ultrasound systems, is the APC850 transducer by APC International of Mackeyville, PA, USA. In one embodiment, the transducers are located on single external device. In another embodiment, the transducers are located on multiple external devices. In one embodiment, the transducers are located on different axis (not necessarily X-Y or Z) . This arrangement provides for variation in the position in all axes (C,U,Z) to allow for 3D position measurement. The relative displacement between the sources is known and may be used for the position calculation.

In one embodiment, the computation of the IVO location relatively to the device may be based on the time differences between the different paths travelled by the acoustic signals between different transmitters or receivers, as detailed below.

According to some embodiments, the computation may be performed by the IVO noting the time differences and calculating the IVO location using a processor located on the IVO. In other embodiments, the IVO may note the time differences, and may transmit this information to another device, such that the computation is done by a processor not located on the IVO.

In another embodiment, the computation may also be performed by a processor external to the IVO, wherein the IVO may receive the acoustic waves from the one or more transducers of the external device and may transmit a return signal. In one embodiment, the return signal may be received by one or more transducers located on the external device. In another embodiment, the location of the IVO may be determined upon the time differences between the time of sending the original signals and the times of receiving the return signals, by a processor located on the external device or by a separate processor not located on the IVO. This arrangement provides for lower energy consumption of the IVO, which leaves the IVO with more energy for performing the treatment, operating for longer time, or any other purpose.

In yet further embodiment, an initial location, which is determined relative to the location of the IVO, may be within the patient's body. For example, for a gastrointestinal (GI) device, the beginning of the GI tract may be determined by monitoring the PH level, or Oxygen (0₂₎ levels which significantly changes as the IVO moves from the stomach to the beginning of the small intestine. In one embodiment, measuring position within a Gastrointestinal tract is done by calculating distance traveled by the IVO from a reference feature (or point) being the entry to the small intestine (the Duodenum) . In one embodiment, the identification of entry to the Duodenum is done by means of pH changes or O2 changes. In another embodiment, the identification of entry to the Duodenum is done by identifying specific small intestine feature (for example - identifying the third curve of the IVO travel pattern)

In one embodiment, the location of the IVO may be determined relative to an external location. In one embodiment, the external device may be shaped as a sticker or a belt having a relatively large member. In another embodiment, the member may be similar to a buckle, to be located over the navel of the patient, wherein all transducers are located on the member. The structure of such belt provides for repeatedly positioning the belt at the same position with high accuracy, such that locations relative to one or more of the transducers, as obtained during the preliminary stage, can be reused. One technical effect of the disclosed subject matter provides for determining the position of an IVO with high accuracy, in a consistent and repetitive manner. The system is inexpensive, does not require expensive equipment and is easy to use.

Another technical effect of the disclosed subject matter relates to the system being safe for use, as it uses acoustic signals for locating the device, which are harmless to human tissues.

Reference is now made to Fig. 1A, showing a patient wearing an external device 104 shaped as a belt, to Figs. 1B-1D showing some views of the external device, and to Figs. 2A and 2B showing distances between transducers of the external device. Fig. 1A shows patient, wearing a belt 104 comprising four transducers: two transmitters 108 and 112, having the same X and Z coordinates and located on one side of the body, transducer 116 located on the other side of the body, and a transducer 120 (not shown on Fig. 1A) located on the back of patient. Transducers 116 and 120 have the same Y coordinate, which is substantially the average between the Y coordinate of transducers 112 and 108. Fig. IB shows a top view, Fig. 1C shows a front view, and Fig. ID shows a back view of the external device comprising the belt 104. By positioning the transducers as detailed above, the relations between the positions of the transducers can be described as follows:

Sio8 = {^_d2, 0, -dz}

Sii₂ = {^_d₂, 0, d_{z }}

Sii6 = {di, 0, 0} and

Si2o ⁼ { 0 , d_y, 0 }

Where Si indicates the 3-dimensional location of transducer I {X, Y, Z } ; the distances are shown in Figs. 2A and 2B; di is an estimated distance between the center of the patient's body along the x axis and transducer 116; d2 is an estimated distance between the center of the patient's body along the x axis and transducers 108 and 112; d_y is an estimated distance between the center of the patient's body along the y axis and transducer 120; and d_z is an estimated distance between the center of the patient's body along the z axis and transducers 108 or 112 (in different directions) . di, d2, d_y and d_z can be estimated in a number of ways, including but not limited to:

1. Physical measurement: d_z can be measured as half the distance between transducers 108 and 112; di, d2 can be estimated by measuring the patient's dimensions or the lengths along the belt 104.

2. Acoustic measurement: can be measured by using the acoustic sources of belt 104. The actual distance between the sources can be determined by measuring the time it takes an acoustic echo to travel from one acoustic waves transducer to the others. The acoustic wave travels at an average speed of 1,540 meters per second inside the human body. By transmitting an acoustic wave from one transducer and receiving it by other transducers, the distance between the source and the destination transducers can be calculated by multiplying the time between transmission and receiving of the wave by the average travel speed. The first echo received can be used, in order to avoid wrong detection of secondary echoes from internal organs, as is the case with ultrasound acoustic waves traveling through the body. For example, if the time between generating the signal by transducer 116 and its reception in transducer 108 is 400 microseconds, the distance is calculated to be 400 *10⁶ *1540 = 61.6cm. It will be appreciated that multiple measures, optionally using different transducers for transmitting the signals, can be taken and averaged to produce a more accurate result.

Reference is now made to Fig. 3 showing graphs of transmitted acoustic wave having frequency of 1MHz as transmitted by transducer 116, and the echo signals received by the other transducers. Graph 300 shows the wave as transmitted by transducer 116, graph 304 shows the wave as received by transducer 120, after time difference of Ti; graph 308 shows the wave as received by transducer 108 after time difference of T2; and graph 312 shows the wave as received by transducer 112, also after time difference of T₂. The corresponding distances Di-_j indicating the distance between transducer i and transducer j are represented below:

D120-116 = sqrt (di² + d_y ²)

D116-112 = sqrt ( (di² + d₂ ²) + d_z ²)

Due-108 = sqrt ( ( di² + d₂ ²) + d_z ²)

D120-112 = sqrt ( ( d_y ² + d₂ ²) + d_z ²)

Once D120-116, D116-112, D116-108 and D120-112 are determined, the four equations with four unknowns can be solved in any numeric or analytic manner. It will be appreciated that the design shown and related to in Figs. 1A-3 is exemplary only and other designs can be used. However, interferences to the wave travel which may be caused by dense objects, such as bones, might reduce the accuracy of the system. Thus, a minimum of three external transducers, is required in order to obtain a 3D position, but employing more transducers may increase the accuracy. In addition, maintaining an arrangement in which .

Reference is now made to Fig. 4 demonstrating an exemplary structure of an acoustic waves transducer, such as transducer 108, 112, 116 or 120 which may be used as described below and above. The transducer may comprise a piezoelectric transducer 400, which can function as a transmitter and/or receiver. Piezoelectric transducer 400 may generate an acoustic signal in response to a trigger originated in system controller 404. The trigger may initiate the generation of an acoustic signal by acoustic signal generator 408. The acoustic signal can be generated in a variety of frequencies, such as, without limitation, tens of KHz to tens of MHz. In one embodiment, the frequencies are in the range from 20KHz to 10MHz. In one embodiment, the frequencies are in the range from 30KHz to

7MHz. In one embodiment, the frequencies are in the range from 40KHz to 5MHz . In one embodiment, the frequencies are in the range from 40KHz to 3MHz . In one embodiment, the frequencies are in the range from 40KHz to 1MHz. In one embodiment, the frequencies are in the range from lOOKHz to 1MHz. In one embodiment, the frequencies are in the range from 200KHz to 1MHz . In yet another embodiment, the frequencies are selected from 20KHz, 40KHz, 60KHz, lOOKHz, 20 OKHz , 40OKHz , 500KHz, 700KHz and 1MHz. Generator 408 uses a digital controlled oscillator, and the signal may be amplified by amplifier 412. The amplified signal is passed to piezoelectric transducer 400. On the reception path, an acoustic echo, which is received by the transducer, is amplified by amplifier 416, and passed on through one or more band pass filters 420, to an analog to digital (A/D) converter 424 and to a digital signal processor (DSP) 428, where the samples are being processed. Controller 404 provides timing and synchronization signals to DSP 428. DSP 428 can perform multiple real-time tasks, for example digitally filtering and detecting a received echo according to its carrier frequency, selected, without limitation from 20KHz, 40KHz, 6OKHz , lOOKHz, 200KHz, 400KHz, 500KHz, 700KHz and 1MHz, or any other acoustic frequency. Positive detection of the echo can be accomplished in one or more manners, such as but not limited to a digital threshold crossing, or cross correlation with a sample of the transmitted acoustic signal .

Determining the location of the IVO relative to the external device can be performed in a plurality of embodiments. In one embodiment, the method is referred to as the "time-stamp", and is based on the computing being performed by a processor located on board of the IVO, or externally to the IVO but wherein information required for the calculation is transmitted by the IVO to an external computing unit. The IVO and external acoustic waves transducers, such as transducers 108, 112, 116 or 120 may have synchronized timers, which use the same time counters, up to a small error. The IVO transducer may receive echoes from the acoustic sources of the external device and may compare the Time of Arrival (TOA) of the echoes with its own internal time stamp. The external transducers and the IVO using the same time counters allows the system to calculate the location of the IVO based on the distances from the external sources, as determined from the time difference between the TOA and the time of transmission as noted by the IVO internal timer. In one embodiment, each external acoustic source may transmit its signal using a different frequency which the IVO can identify. A non-limiting example is transmission of signal by the transducers with the following frequencies: transducer 108: 1MHz, transducer

112: 1.2MHz, transducer 116: 1.4MHz and transducer 120:

1.6MHz. In one embodiment, all transmissions are done on a predetermined time interval. in one embodiment, the predetermined time interval is in the range of 200micro- seconds to 10 seconds. In another embodiment, the predetermined time interval is dictated by the internal time counters configured to pass through a certain value. The received echoes TOAs represent the time the signal traveled within the body from the acoustic source to the IVO, for example: Ti would be the time elapsed between transducer 108 transmission and reception in the IVO, T₂ would be the time from transducer 112, T3 would be the time from transducer 116, and T4 would be the time from transducer 120. If the position calculation, including determining the distance from each transducer and then its location, is done locally on the IVO, the results may remain internally in the IVO, or may be transmitted to another destination. If the position calculation is carried out externally to the IVO, the IVO may transmit the time measurements through a wireless communications channel, or any other available communication channel, to an external processor or computing element.

Reference is now made to Fig. 5, showing an exemplary structure of the IVO circuit 500 configured to implement the "time-stamp" mode. Acoustic signals transmitted by a transducer of the external device may be received by piezoelectric transducer 516, and may be amplified by amplifier 520, passed through a low-pass (or band pass) filter 524, such as a Nyquist filter, and delivered to an A/D converter 528. A/D converter 528 may sample at a rate which is higher than the expected input signal. For example, if the expected input signal is a 1MHz echo signal, A/D converter 528 may sample in a 1 OMSamples/Sec rate, in order to allow for much higher than Nyquist sample rate in further calculations. The samples may be fed into a digital signal processor (DSP) 512 for processing and calculations. Time stamps may be generated by time counter 508. Time counter 508 may be a binary counter which is synchronized with counters of the transducers of the external device, wherein all counters are driven by a clock derived from an oscillator 504, such as a crystal oscillator having low drift over time and temperature, for example - 10 parts per million. Each acoustic echo which arrives to and is identified by the transducer of the IVO circuit is compared to the time stamp generated by time counter 508. Once the time differences are calculated for the echo of each transmitter, the IVO can either calculate its exact position using the DSP 512, or send the time difference information to an external computer, using an on-board transmitter, such as communication unit 532, such as an RF transmitter implementing Bluetooth protocols. The signal carrying the information may be amplified by amplifier 536 and transmitted via antenna 540. The external computer may calculate the IVO position based on the relative location of the transducers, which determination is detailed above, and the echo signal differences: Ti, T₂, T₃, and T₄ in the exemplary structure of belt 104 having four transducers emitting four acoustic signals . In order to ensure that the time stamp counters of transducers of the external device and the IVO are synchronized, the IVO may undergo a reset process prior to insertion of the IVO. The reset process may be performed in association with the transducers of the external device, such that all counters are started simultaneously. In an exemplary embodiment of the reset process, the IVO may include contacts adapted to connect it to reset circuit 500. Prior to insertion of the IVO into the bodily lumen, the IVO may be connected to the external device controller, which can be implemented as part of one of the belt transducers, and once connection is established, the counter circuit of the IVO and counter circuit of the external transducers are reset to zero state. Once the IVO is disconnected, both counters may start counting, each based on its own timer. Since the timers are identical, they may continue triggering at the same time intervals for a time period which may be sufficient at least for the expected duration of the procedure .

Referring now to Fig. 6, showing an exemplary block diagram of the external device, such as belt 104 of Fig. 1A, and the associated transducers. Clock source 600 such as an oscillator, reset circuit 604 and time counter 608 may be implemented as described in association with Fig. 5 above, to provide that all transducers, such as transducer 108, transducer 112, transducer 116, and transducer 120 are synchronized therebetween, and with time counter 608 of the IVO. Once time counter 608 reaches a pre-defined value, a trigger may be issued simultaneously by the transducer controller unit 612 to all transducers, via a trigger signal. Once the trigger signal is fired, each transducer may produce its unique acoustic signal. It will be appreciated that other methods may be used for triggering and controlling the acoustic signal generation. For example, a staggered trigger may be generated, in which each transducer generates an acoustic signal in a fixed and known delay, for example lOOmSec relative to the other transducers. Using known delays, all transducers can use the same frequency, since a time-based separation exists between the signals, and the computing unit may be configured to deduct the known delays from the measured time differences, in order to retrieve the real time delay for each signal and hence the distance to its source . When the computation of the position is done externally, for example by a processor located on the belt or by an external computer, an RF receiver comprising an antenna 632 and a communication protocol decoder 636 are required in order to receive the time differences detected by the IVO and use them for calculating the IVOs position on processor 640.

Reference is now made to Fig. 7, showing a flowchart of steps in a method for determining the position of an IVO, in accordance with the "time stamp" embodiment as disclosed above.

A transducer associated with an IVO and transducers associated with an external device are reset or synched, such that their time counters are synchronized 704. Step 704 may be performed as close as possible to step 708, for example immediately prior to step 708. The IVO is inserted or otherwise applied into a bodily lumen of a patient 708. Optionally, the external device is located close to the patient, for example by placing a belt around the patient, optionally with coupling gel provided between the patient's skin and the belt. At a predetermined time, an acoustic signal may be sent from one or more transducers located on the external device, such as the belt 712. Once an echo of the acoustic signal (s) is received by the transducer associated with the IVO, the IVO notes the receiving time 716.

A processor such as DSP of the IVO then may calculate the time difference between the predetermined time at which the signal is known to have been sent, and the receiving time. The time difference may also be associated with the transducer that transmitted the signal. The association can be performed, for example, in accordance with the specific delay/frequency of the received signals and the known delays/frequencies associated with the transducers 720. The processor may then determine whether echo signals have been received from all, or sufficient number of transducers associated with the external device 724. If not all, or insufficient number of signals have been received, control may return to step 716, at which additional signals may be received. If all or sufficient number of signals have been received, then on step 728 it may be determined, for example by the DSP whether the position is to be determined by a processor located within the IVO, or by another processor operatively connected thereto. If the position is to be determined by a processor associated with the IVO, then on step 736 the IVO position may be calculated, and the process may repeat for determining subsequent locations. Otherwise, the time differences or another partial computation result may be transmitted, for example using communication unit to the processor. The process may repeat for determining subsequent locations .

Reference is now made to Fig. 8, showing an exemplary illustration of the transmitted and received signals in the "transponder", a location determination of the IVO relative to the external device which allows for all computations to be performed externally to the IVO, such that the IVO does not require significant computing resources. It will be appreciated that all mentioned frequencies are exemplary only, and other frequencies may be used.

In the "transponder", the IVO includes a repeater circuit, which detects an echo transmitted from one of the transducers associated with the external device, and transmits a signal back, either immediately or after a predetermined delay. The transducers may receive the repeated echo and calculate the travel time of the acoustic signal, by dividing the difference between the transmission and reception time by two, since the echo traveled the distance to and from the IVO. To avoid ambiguity, it may be required to verify that the echoes received by the transducers are indeed transmitted by the IVO and are not received from other reflection sources in the body. For that purpose, in one embodiment, each transducer transmits the signal at a predetermined frequency (PDF), on a separate time slot, and the IVO repeats the echo with a different frequency PDF+XKHz . Thus, the transducer can measure the time between sending the signal and receiving the true echo and divide it by 2. In one embodiment, each transducer may use a different frequency, and the IVO may send a shifted frequency. A non-limiting example of such transduction is transducer 108 transmitting a signal on PDF and the IVO responding on PDF+100KHZ, transducer 108 transmitting on PDF+200KHZMHz and IVO responding on PDF+300KHZ, or any other combination. For the purpose of this example, the first option, related to time slot differentiation is used. Reference is now made to Fig. 8. Transducer 108 transmits a signal 800 at a PDF. Signal 804 is repeated back by the IVO on a different frequency of PDF+200KHZ. The time between transducer 108 transmission and echo signal reception from IVO is Ti. Additional echoes 808 may be received by transducer 108 from other reflection items, but those would be in PDF frequency, thus transducer 108 can easily discard them. After a predetermined time, which is based on the maximum acoustic signal travel time applicable for this scenario, transducer 112 may transmit an acoustic signal 812 at a PDF, and a repeated signal 816 is received from IVO at PDF+200KHz. The time difference between transmission and reception is T2. After a predetermined time, transducer 116 may transmit a signal 820 at a PDF, wherein echo 824 is repeated at PDF+200KHz by the IVO at time delay of T3. Additional echoes 828, 832, may be received at a PDF from other reflection sources.

Transducer 120 may transmit a signal 836 of a PDF for example, wherein echo 840 is repeated by the IVO at PDF+200KHz. Additionally, a preceding echo 844 from another source which is also at the PDF may be received. For better accuracy of the distance calculation, a programmable delay line, or similar method of controlled delay, can be used within the IVO. The delay can be programmed during manufacturing, or any time prior to the in-vivo use of the IVO, to verify that the time elapsed between reception of acoustic signal by the IVO, and the transmission of the repeated signal remains constant.

Reference is now made to Fig. 9, illustrating an exemplary structure of the IVO circuit operating in accordance with the transponder implementation. Piezo transducer 900 may receive an acoustic signal transmitted by an external device transducer, amplify it using amplifier 904 and pass it on to detector 908 which can be an analog or digital detector. Once the signal is positively detected by detector 908, a detection indication signal is generated at the output of detector 908. The signal may be input into a programmable/adjustable delay circuit 912. The indication signal may be delayed in accordance with pre defined timing, in the range of, 200pSec to lOSec. In one embodiment, the pre-defined timing is selected from 200pSec, 300pSec, 400pSec, 500pSec, 600 pSec, 700 pSec, 800 pSec, 900 pSec, lmSec, 5Sec, lOmSec, 20 mSec, 50 mSec, 100 mSec, 250 mSec, 500 mSec, 750 mSec, lSec, 5Sec, and lOSec. The delay may be calibrated during production or deployment of the IVO . The delayed indication signal may then be used to trigger a transmission signal, which may be of a different frequency than the received signal. The signal may be generated by signal generator 916, amplified by amplifier 920 and passed on to piezo transducer 924 for transmission, such that it can be received by the external device transducer. It will be appreciated that piezo receiver 900 and piezo transmitter 924 can be implemented as one component .

The difference between the times, for example Ti, T₂, T₃ and T₄ of Fig.8, at which each signal is transmitted and received, may be divided by two to obtain the acoustic signal travel time, and may be divided by the speed of sound of acoustic waves in human tissue (1540 m/sec), to obtain the distance between each external device transducer and the IVO. When subtracting the pre-set delay (Td) the distance can be written as:

Di = ( (Ti-Td) ) / (2*1540) , wherein l<=i<=N, N is the number of transducers, and T± is the specific round trip time. In one embodiment, In order to calculate the IVO location, in either the "time stamp" or the "transponder" implementations, four external device transducers may be used, such that four distances are calculated: Di through D₄. The IVO location may be denoted as {x, y, z}, and the location of the i-th transducer may be denoted as {x±, y±, Zi}. The locations of the transducers may be determined as detailed above. The following equations describe the relationship between the IVO location and the transducers' locations :

( X 1^— X ) ² + yi-y)² + (zi-z) ² (Di+ e · 1540) ² (X2-X)² + y₂-y) ² + (z₂-z)² (D₂+ e · 1540) ² (x₃-x)² + ys-y) ² + (z₃-z)² (D₃+ e · 1540) ²

(X₄-X)² + y4-y) ² + ( Z 4^— Z ) ² (D₄+ e · 1540) ²

The four equations can then be solved for the four unknowns, x, y, z, and e, wherein e is a timing error, which is multiplied by the sound speed in the tissue (1540 m/s) to compensate for the difference between the different clocks in the "time stamp" implementation, or between the delays in the IVO in the "transponder" implementation .

In one embodiment, transponder implementation may be used with a simplified external device. In one embodiment, unlike the device shown in Fig. IB, which has the transducers located at substantially distant locations around the body, the external device is a belt having a member designed to be positioned over the patient's navel. In one embodiment, at least one transmitter and a plurality of receivers, are located on the member, within a relatively short diameter. In one embodiment, the transmitter and receiver are performed within the same transducer, in another embodiment the diameter is in the range of 0.5cm to 60cm, 1cm to 20cm, 2cm to 10cm. Since the member is located over the patient's navel, it is relatively easy to re-position the member at substantially the same location, with relatively high accuracy, especially when the repositioning is done within a short time period, for example up to a few days from a previous positioning .

In yet further embodiment, the transducer may transmit a single acoustic pulse. In one embodiment, the single acoustic pulse in the range of 420Hz to 10MHz. In another embodiment, the single acoustic pulse may be repeated by the transponder on the IVO, at the same frequency or at a different frequency. In one embodiment, the receivers located within the member may receive and amplify the echoes to obtain positioning data.

Reference is now made to Fig. 10A-C. Fig. 1A illustrates a patient with a belt 1000 on, wherein the belt 1000 comprises a member 1004 located over the navel of patient. Fig. 10B shows a schematic illustration of the member 1004, comprising transducer 1008 operating as a transmitter and four transducers operating as receivers: Rxl 1012, Rx2 1016, Rx3 1020 and Rx4 1024. In one embodiment, transducers 1012, 10106, 1020 and 1024 operating as receivers are arranged at the same distance from the transducer operating as transmitter. In yet further embodiment, the lines connecting each receiver with the transmitter are at 90 degree intervals, such that Rxl 1012, Tx 1008 and Rx2 1016 are along a first straight line, Rx3 1020, Tx 1008 and Rx4 1024 are along a second straight line, wherein the first and the second lines are perpendicular to each other. Fig. 10C shows an illustration of another schematic embodiment of the member 1004, comprising transducer - 1-0-0-8 operating as a transmitter and three transducers operating as receivers: Rxl 1012, Rx2 1016, and Rx3 1020. In one embodiment, receivers 1012, 1016, and 1020 are arranged on the corners of a right triangle, at the same distance from the transmitter. In one embodiment, receivers Rxl 1012 and Rx 2 1016 may be used for detecting the angular distance from the signal source on one plane (for example Q) , while Rxl 1012 and Rx3 1020 may be used for detecting the angular distance from the signal source on another plane (for example cp) , in similar manner to the disclosure above. In one embodiment, each echo returned from the IVO may be tagged with a time of arrival (TOA) tag. The TOA tag is the time since the signal was transmitted until the echo from the IVO is received.

Reference is now made to Fig. 11 showing a schematic graph 1100 of the transmitted signals, and the four graphs of the received signals: graph 1104 of the signal received by Rxl 1012 of Fig. 10 after a time difference of Ti, graph 1108 of the signal received by Rx2 1016 of Fig. 10 after a time difference of T₂, graph 1112 of the signal received by

Rx3 1020 of Fig. 10 after a time difference of T3, and graph 1116 of the signal received by Rx4 1024 of Fig. 10 after a time difference of T₄. It will be appreciated that Ti, T₂, T3 and T4 as shown are exemplary only, and any one of them can be longer or shorter than any other one.

In one embodiment, a minimum of two transducers operating as receivers, are located along one line on one plane, which provides for variation in the position in all axes {C,U,Z} if two perpendicular planes are used, to allow for 3D position measurement. In yet another embodiment, the receivers may be placed along the body' s circumference to allow better reception of the acoustic signal, as some piezo transducer might have directional sensitivity and are transmitting and receiving signals from certain range of angles only. In one embodiment, the position of the IVO may be determined in polar coordinates, comprising a distance between the IVO and a predetermined point such as the middle of transmitter 1008 of Fig. 10, and two angles, Q and cp. In another embodiment, distance between the middle of transmitter 1008 of Fig. 10, and the IVO may be calculated by summing the travel time from all receivers and multiplying by the sound speed in the body, dividing by 4 since the sum includes four distances, and dividing by two since each travel time represents the round-trip time. T_d may be a predefined delay in the IVO. In one embodiment, T_d, which is the built-in delay of the IVOs response to the Tx signal, may be set to zero.

In one embodiment, the arrival angle of the echo signal repeated by the IVO may be determined by comparing two travel times associated with detectors within the same plane .

Reference is now made to Fig. 12 showing a schematic illustration of the angle measurement for a system comprising the device of Figs. 10A-B. in one embodiment, the distance di between IVO 1200 and Rxl 1012, and the distance d₂ between IVO 1200 and Rx2 1016, wherein Rxl 1012 and Rx2 1016 are aligned along a line passing through T_x 1008. L is the vertical distance between Rxl 1012 and Rx2 1016. Thus, the cosine of the arrival angle may be estimated as:

In one embodiment, cos (cp) can be estimated in the same manner using the distances to Rx3 1020 and Rx4 1024 of Fig. 10A-B, and the horizontal distance therebetween. In one embodiment,, V(t,D,e,<p) is a vector in which D is the distance from the member to the IOV, Q and cp are the horizontal and vertical angles to the IOV, and t represents the point in time in which this vector was obtained. The polar coordinates R, Q and cp can be converted to an {X, Y, Z } representation relatively to the transmitter, to a point within the user's body or to any other point. Tracking the IVO can be performed in either coordinate system.

In one embodiment, the velocity of the IOV can also be calculated by subtracting two sequential vectors and dividing by the difference between the times at which they have been obtained. In another embodiment, the distance traveled by the IOV may be calculated by subtracting the X, Y and Z points in each detection segment, thus obtaining the distance traveled in a specific segment, integrating all of these segments yields the travel distance. In yet further embodiment, 3-dimensional location can be retrieved by triangulation techniques, both in the XY plane and in the XZ plane.

According to the aspects of the invention, the disclosed subject matter can be used for numerous procedures and applications. In one embodiment, the described system relates to the positioning and tracking of an electronic capsule traveling within the GI tract. In another embodiment, the use of such capsule can be the delivery of a drug or a certain treatment to a specific area of the GI tract. In one embodiment, an endoscopic capsule is traveling using the natural peristaltic through the intestine, while taking images of the inner intestine. In yet further embodiment, the capsule is such as the SB-3 capsule provided by Medtronic of Minneapolis, Minnesota, USA. In one embodiment, the images are transmitted wirelessly to an external image recorder, for diagnostic purposes. In yet further embodiment, a transducer added to the capsule for mapping the patient's intestine, and associating a three-dimensional position with each recorded image, thus creating a "personal tract". In one embodiment, the positions may be relative to any internal point. In one embodiment, the internal point is the beginning of the small intestine. In another embodiment, the internal point is a turn in the small intestine. In yet further embodiment, the internal point is the 4^th turn in the small intestine. In another embodiment, the positions may be relative to any external point. In one embodiment, the external point is a transducer operating as a transmitter located over the navel of the patient, which can be repositioned with high accuracy.

In one embodiment, an initial diagnostic and recording session may be performed, in which an abnormality such as a lesion, an area that requires light therapy, or the like, may be detected, and its exact location within the GI tract may be recorded and associated with the personal tract data. Following the initial diagnostic and recording session, a 3D description of the patient's intestine may be available.

It will be appreciated that although the description focuses on the intestine, it is equally applicable to any other bodily lumen traversed by an IVO. When a certain location-dependent treatment, such as an endoscopic surgery, heart catheterization, Low Level Light Therapy, drug dispensing, or sample collection is required, then once the personal tract is recorded, a second capsule (or multiple capsules over time) or another IVO can be inserted into the lumen. The treatment can be initiated when the IVO reaches the required location, thus making the treatment safer, more effective and focused on the target area. It will be appreciated that the location can be expressed in a plurality of ways, for example C,U,Z format, or R, Q, cp format, or as the collection of time stamps or delays between transmission and reception for each transducer as shown in Fig 11 by Th, T_2, and so on, which are quantitative representations that are relative to the belt position. Additionally, or alternatively, the location can be described in a fully relative manner, for example, "the device has passed the 3^rd intestine curve", "after 2 left turns and 1 right turn heading front side", or the like.

The positioning of the external belt including the transducers can slightly vary between uses, resulting in shift of the axis's origin point, and in a personal tract which is shifted, tilted or otherwise located differently than the original recorded tract. It may thus be required that the recorded tract is aligned with the pre-recorded personal tract. In order to align the tracts, a few methods may be used. If lesion location is diagnosed and provided in absolute distance from the entrance to the small intestine - results are not sensitive to belt position as distance is calculated for IVO activation and not absolute XYZ position. In one embodiment, the method can include aligning the pre-recorded personal tract and the current personal tract by registering images from the two tracts, in accordance with reference points that are associated with features, such as specific intestine curves. Aligning may include rotating and/or scaling (possibly with different scales for different dimensions) one or more images of the personal tract or the recorded tract. Alignment can take place once, for example at the beginning of the second IVO travel through the bodily lumen, to obtain an initial alignment. Additionally, or alternatively, the alignment can be repeated when the IVO reaches one or more noticeable features, such as a curve of the intestine. As more data are collected, for example after the IVO passes through several curves, the alignment accuracy may increase.

In another embodiment, the method may relate to ongoing or periodical 3D image cross-correlation performed between the original recorded tract and the tract generated as the second or subsequent IVO moves within in the bodily lumen.

It will be appreciated, however, that alignment is not mandatory, as information can also be derived from the personal recorded tract. For example, if a point of interest, such as a lesion is indicated at a certain location within the GI tract, the distance travelled by the IVO from the beginning of the tract can be estimated. When the IVO reaches the required location, it may be activated in accordance with the procedure or treatment to be performed. For example, a lesion may be detected by a diagnostic capsule around a point which is 57cm from the beginning of the tract (which may be detected using the PH or O2 change) . The distance travelled by the second or further IVOs can be calculated, and once the IVO reaches the 57cm point, its activity can be initiated.

Reference is now made to Fig. 13, showing a flowchart of steps in a method for utilizing location information received from an IVO for carrying out localized treatment or procedure. On step 1300, a description of a bodily lumen may be obtained. The description can be received online from a system, retrieved from a storage device, or the like. In one embodiment, the description may include one or more images associated with certain locations within the bodily lumen. In another embodiment, the description may comprise a sequence of locations relative to a point internal or external to the bodily lumen. In one embodiment, obtaining the description may include generating the description on a preliminary mapping stage, for example by a system as described above. It will be appreciated that generating the description can use multiple readings from one or more points or nearby points, such that samples may be averaged or otherwise combined for greater accuracy. It will also be appreciated that the obtained description can be generated, adjusted or enhanced in accordance with data from other sources such as known features, features associated with the specific person, previous mappings of the person, or the like. On step 1304, an indication to a location within the bodily lumen at which an action is to be performed, such as applying a treatment, or another procedure may be received. The location indication may be received from a professional using the obtained description, or from any other source. On step 1308, after an IVO has been inserted into the bodily lumen, a current location within the bodily lumen may be received from the IVO system. The IVO system comprises an external device positioned externally to a body of the patient, the external device comprising at least one acoustic waves transmitter; an IVO comprising at least one acoustic waves receiver; a controller for controlling the transmission of acoustic waves by the acoustic waves transmitter; and a processor configured to determine a location of the IVO, based on time differences between transmission times and receiving times of acoustic waves, wherein the at least one acoustic waves transmitter and at least one acoustic waves receiver include at least five acoustic waves receivers or transmitters. It will be appreciated that step 1308 may be repeated and locations may be repeatedly received from the system, for example every predetermined period of time. On step 1312, it may be determined whether the current location is substantially equal to the location received on step 1304. In one embodiment, the distance does not exceed a predetermined threshold from the location received on step 1304. If the current location is indeed the same as the location indicated for the treatment, then on step 1316 the procedure or treatment may be applied. In one embodiment, further location readings may be received from the IVO until the IVO stops, exits the bodily lumen, its power source is exhausted, or the like. The steps of Fig. 13 can be performed automatically by a system comprising a processor. The system may comprise or be in communication with a storage device storing commands and/or data such as the bodily lumen description or the treatment location. The system may further be in communication with a source providing the position of an IVO as described above. In some embodiments, the processor may be located on the external device described above. In some embodiments, the processor may be the same processor that performed the location calculation, in one embodiment, the processor can be a Central Processing Unit (CPU) , a microprocessor, an electronic circuit, an Integrated Circuit (IC) or the like. The storage device may be a hard disk drive, a Flash disk, a Random Access Memory (RAM) , a memory chip, or the like. In another embodiment, the system may also comprise an Input/Output (I/O) device which may be utilized to provide output to and receive input from a user such as a caregiver. The I/O device may be used, for example, for providing human approval for initiation of the treatment. The I/O device may be a keyboard, a mouse, a touch screen, a microphone, a speaker, a display device, or the like.

In one embodiment of the invention, a minimum of 3 transducers on the same plane, and a minimum of 2 perpendicular planes (total of five transducers) are required to obtain the IVO 3D location based on triangulation only with no need for travel time measurement. By measuring the received signal phase shift between receivers located on the same plane, two angles can be obtained (an angle from each neighboring pair of receivers), thus obtaining the ability to calculate the point where the angles meet for each plane, which allows for localization of the IVO by means of triangulation.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms "a, " "an" and "the" are intended to include plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms

"comprises" or "comprising," when used in this specification, specify the presence of stated features, integers, steps, operations, elements components and/or groups or combinations thereof, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components and/or groups or combinations thereof. As used herein the terms

"comprises", "comprising", "includes", "including", "having" and their conjugates mean "including but not limited to". The term "consisting of" means "including and limited to".

As used herein, the term "and/or" includes any and all possible combinations or one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative ("or") .

Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the specification and claims and should not be interpreted in an idealized or overly formal sense unless expressly so defined herein. Well-known functions or constructions may not be described in detail for brevity and/or clarity.

It will be understood that when an element is referred to as being "on, " "attached" to, "operatively coupled" to, "operatively linked" to, "operatively engaged" with, "connected" to, "coupled" with, "contacting," etc., another element, it can be directly on, attached to, connected to, operatively coupled to, operatively engaged with, coupled with and/or contacting the other element or intervening elements can also be present. In contrast, when an element is referred to as being "directly contacting" another element, there are no intervening elements present.

It will be understood that, although the terms first, second, etc., may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. Rather, these terms are only used to distinguish one element, component, region, layer and/or section, from another element, component, region, layer and/or section. Certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements .

Throughout this application, various embodiments of this invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range .

Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases "ranging/ranges between" a first indicate number and a second indicate number and "ranging/ranges from" a first indicate number "to" a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.

All publications, patent applications, patents, and other references mentioned in the disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains. In case of conflict, the patent specification, including definitions, will prevail. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. Throughout this application various publications, published patent applications and published patents are referenced.

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 by the appended claims and includes both combinations and sub-combinations of the various features described hereinabove as well as variations and modifications thereof, which would occur to persons skilled in the art upon reading the foregoing description .

Claims

CLAIMS What is claimed is:

1. An in-vivo object (IVO) location determination system, comprising :

an external device adapted to be positioned externally to a body of a patient, the external device comprising at least two acoustic waves transducers configured to transmit or receive an acoustic wave; an IVO comprising at least one acoustic waves transducer configured to receive or transmit an acoustic wave; a controller for controlling the transmission of acoustic waves; and, a processor configured to determine a location of the IVO relative to the external device.

2. The system of claim 1, wherein the location is determined based on the time differences between transmission times and receiving times of the acoustic waves .

3. The system of claim 1, wherein the location is determined based on phase differences between the received acoustic signals.

4. The system of any one of claims 1 to 3, wherein at least two acoustic wave transducers of the external device are located on the same plane.

5. The system of any one of claims 1 to 4, wherein the external device is in a form of a flexible belt designed to be worn by the patient.

6. The system of Claim 5, wherein the belt comprises at least three transducers configured to transmit and receive the acoustic wave.

7. The system of Claim 6, wherein the transducers are arranged such that at least one pair of acoustic wave transducers has at least one common Cartesian coordinate .

8. The system of claim 6, wherein the first pair of transducers has at least one common Cartesian coordinate, and the second pair has at least two common Cartesian coordinates.

9. The system of any one of claims 6 to 8, wherein the at least one transducer of the IVO receives acoustic waves transmitted by the at least two transducers of the external device, and responds by transmitting the corresponding acoustic signal to be received by the one or more acoustic waves transducers of the external device, and wherein the calculation of the position is performed on the external device.

10. The system of claim 9, wherein the corresponding signal is transmitted immediately upon reception of the signal by the IVO.

11. The system of claim 9, wherein the corresponding signal is transmitted following a predetermined time interval upon the reception of the signal by the IVO.

12. The system of any one of claims 6 to 8, wherein the at least one transducer of the IVO receives acoustic waves transmitted by the at least two transducers of the external device, and wherein the position calculation is performed on the IVO.

13. The system of any one of claims 4 to 12, wherein the acoustic waves transmitted by the at least two acoustic waves transducers are transmitted in separate time slots .

14. The system of any one of claims 6 to 13, wherein the acoustic waves transmitted by the at least three acoustic waves transducers have different frequencies.

15. The system of any one of claims 6 to 14, wherein the belt further comprises a member designed to be placed over the navel of the patient, wherein the member comprises at least one transducer configured to transmit the acoustic wave and at least three transducers configured to receive the acoustic wave, wherein the at least three transducers configured to receive the acoustic wave are located on the same plane with the at least one transducer configured to transmit the acoustic wave.

16. The system of any one of claims 6 to 15, wherein the processor is configured to determine an average of distances between the transducer of the IVO and each of the at least three transducers of the external device.

17. The system of any one of claims 6 to 16, comprising at least four transducers configured to receive the acoustic wave.

18. The system of claim 17, wherein the first pair of the at least three transducers configured to receive the acoustic wave are on a first plane, and a second pair of the at least four transducers configured to receive the acoustic wave are on a second plane, and wherein the second plane perpendicular to the first plane.

19. The system of Claim 18, wherein the processor is further configured to determine a first angle between a line connecting the transducer of the IVO and the first plane, and a second angle between a second line connecting the transducer of the IVO and the second plane .

20. The system of Claim 6, wherein the at least one transducer of the IVO receives the acoustic waves transmitted by the at least one of the three transducers of the external device, and the location of the IVO is determined in accordance with the travel times between the at least one transducer of the IVO and each of the at least three transducers of the external device.

21. The system of Claim 20, wherein the processor is located on the IVO.

22. The system of Claim 20, wherein the processor is located externally to the IVO.

23. An IVO location determination system, comprising

an external device configured to be positioned externally to a body of a patient, wherein the external device is designed as a belt to be worn by the patient, wherein the belt comprises a member designed to be placed over the navel of the patient, wherein the member comprises at least one transducer configured to transmit an acoustic wave and at least three transducers configured to receive an acoustic wave, .

24. The system of claim 23, wherein at least three transducers configured to receive an acoustic wave are located in the vicinity of the transducer configured to transmit an acoustic wave.

25. The system of claim 23 or 24, wherein each of at least three transducers configured to receive an acoustic wave are further configured to operate as receivers of the acoustic wave.

26. The system of any one of claims 23 to 26, comprising at least four transducers.

27. The system of claim 26, wherein a first pair of the at least four transducers are on a first plane, and a second pair of the at least four transducers are on a second plane, and wherein the second plane is perpendicular to the first plane.

28. A method of treating a patient in need comprising

a) receiving an indication to a location within a bodily lumen at which a treatment is to be performed;

b) providing a first IVO to be internalized by the patient, wherein the first IVO is configured to provide the treatment to the patient;

c) determining the location of the IVO by the location determination system comprising: an external device positioned externally to the body of the patient, wherein the external device comprises at least two acoustic waves transducers configured to transmit the acoustic wave; an IVO inserted into a bodily lumen of the patient, wherein the IVO comprises at least one transducer configured to receive the acoustic wave ;

a controller for controlling the transmission of acoustic waves by the at least one acoustic waves transducer of the external device; and

a processor configured to determine the location of the IVO relative to the external device, based on time interval between transmission times and receiving times of the acoustic waves; and d) Providing the treatment by the IVO at the location where treatment is needed.

29. The method of claim 28, wherein the treatment is selected from the group consisting of endoscopic surgeries, heart catheterization, applying Low Level Light Therapy by an intestine capsule, drug dispensing, and sample collection.

30. The method of claim 28 or 29, further comprising the step of generating the mapping of the bodily lumen using a second IVO, such that each location within the bodily lumen is associated with at least one image.

31. The method of Claim 30 wherein the second IVO comprises an image acquisition unit, and wherein at least one image acquired by the image acquisition unit is associated with a location of the second IVO at the time of image acquisition.

32. The method of Claim 30 or 31, wherein the location of the second IVO is provided relatively to a bodily feature .

33. An IVO comprising:

at least one acoustic waves transducer;

a controller for controlling the transmission of acoustic waves by the at least one acoustic waves transducer; and

a processor configured to determine a location of the IVO based on time interval between receiving times of acoustic waves by the at least one acoustic waves transducer, wherein the acoustic waves are transmitted by at least three acoustic waves transducers located on an external device configured to be positioned externally to the body of a patient.

34. The IVO of claim 32, for use as a therapeutic tool.

35. The IVO of claim 32, for use as a diagnostic tool or a lumen mapping tool .