Patent Application
20240122494
Embodiments of the present disclosure relate generally to electronics and medical diagnostic technology and, more specifically, to techniques for assessing cancerous tissue during surgical biopsies.
In conventional practice, to provide an accurate cancer diagnosis of a suspect lesion, a physician takes one or more biopsy tissues samples from the suspect lesion with either a forceps device or needle device. The tissue samples are then sent for pathological analysis to an outside lab that may not provide the physician with a pathological assessment for multiple days or weeks. Typically, the physician takes multiple samples to increase the likelihood of capturing enough of the suspect tissue for an accurate diagnosis. However, there is nevertheless a relatively high likelihood that adequate sampling of the suspect lesion has not occurred, resulting in a non-diagnostic biopsy measurement that fails to indicate whether the lesion is cancerous or non-cancerous. For example, for numerous cancers, the rate of non-diagnostic biopsy measurements can be as high as 40%. The fact that suspect lesions are usually heterogeneous in nature and that suspect lesions also are typically not directly visible to the physician are two reasons why the percentage of non-diagnostic biopsy measurements is so high. Compounding these issues is the fact, noted above, that the physician usually has to wait days or weeks to receive the biopsy results.
Because a timely diagnosis of many cancers is critical for successful treatment, the ROSE (Rapid On-Site Evaluation) procedure has been developed to determine whether the quality of biopsy tissues samples is sufficient for subsequent pathological analysis. In the ROSE procedure, an onsite pathologist performs pathological analysis of biopsy tissues as they are taken from the patient by the physician, thereby providing more immediate feedback to the physician who is performing the biopsy. This procedure enables a physician to perform additional biopsies and/or change the region of patient anatomy being biopsied when non-diagnostic or non-cancerous measurements occur.
One drawback to the ROSE procedure is that the procedure can alter or consume a significant portion of each tissue sample tested. In that regard, a ROSE pathologist typically prepares slides of a tissue sample for microscopic evaluation by rubbing the tissue sample with the slide. Because the microscopic evaluation of the ROSE procedure benefits from more tissue on the slide, a substantial portion of a given tissue sample is oftentimes used to perform the procedure. As a result, the reliability of subsequent pathological analyses that are performed using the same given tissue sample can be adversely affected.
Another drawback to the ROSE procedure is that the procedure can be disruptive to the workflow of the physician who is performing the biopsy. While the ROSE procedure enables a biopsy physician to take additional samples in response to non-diagnostic tissue samples, the pathological analysis of each sample causes a delay on the order of ten minutes or more. Accordingly, the ROSE procedure can significantly interrupt a biopsy procedure, particularly if a large number of tissue samples are needed to complete the ROSE procedure. These types of interruptions can substantially increase the time needed to perform and complete a biopsy procedure, which increases the clinical resources needed to perform and complete the biopsy procedure and is also highly undesirable for the patient.
As the foregoing illustrates, what is needed in the art are more effective techniques for assessing tissue samples during surgical biopsies.
Embodiments are disclosed for medical devices. In various embodiments, a medical device includes: a tissue sample-receiving surface; an electrode array that includes a first electrode and a second electrode that are positioned to contact a tissue sample disposed on the tissue sample-receiving surface; and an impedance bridge that is communicatively coupled to the electrode array.
Embodiments are disclosed for analyzing a tissue sample. In various embodiments, a method includes recording, at one or more frequencies, one or more impedance measurements associated with an electrode array included in a medical device, wherein the electrode array includes a first electrode that contacts the tissue sample while disposed on a tissue sample-receiving surface and a second electrode that also contacts the tissue sample; determining, based on the one or more impedance measurements, a tissue type of the tissue sample; and causing an indicator of the tissue type to be displayed.
At least one technical advantage of the disclosed design and techniques relative to the prior art is that the disclosed design and techniques provide immediate, real-time feedback to a clinician who is performing a surgical biopsy. Consequently, when a tissue sample is determined to be non-diagnostic via the disclosed design and techniques, the clinician can immediately take one or more additional tissue samples, thereby avoiding the long delays in diagnosing non-diagnostic tissue samples that are typical with conventional approaches. In addition, because the disclosed design and techniques provide feedback to physicians within seconds, the workflow of a surgical biopsy procedure is not substantially impacted, and the duration of the surgical biopsy procedure is not significantly extended. A further technical advantage of the disclosed techniques is that tissue samples taken by a clinician are not altered; therefore, the reliability of subsequent pathological analyses are not adversely impacted. These technical advantages provide one or more technological advancements over prior art approaches.
For clarity, identical reference numbers have been used, where applicable, to designate identical elements that are common between figures. It is contemplated that features of one embodiment may be incorporated in other embodiments without further recitation.
In the following description, numerous specific details are set forth to provide a more thorough understanding of the various embodiments. However, in the range of embodiments of the concepts includes some embodiments omitting one or more of these specific details.
Sample module 120 holds a tissue sample (not shown) and contacts the tissue sample with a first electrode 121 and a second electrode 122 of an electrode array 126, so that an impedance scan of the tissue sample can be performed. In the embodiment illustrated in
Sample module adapter 130 communicatively couples sample module 120 to impedance bridge 140. Thus, sample module adapter 130 electrically couples first electrode 121 and second electrode 122 to appropriate electrical contacts that are associated with impedance bridge 140. In some embodiments, multiple different configurations of sample module 120 can be employed with medical device 100. In such embodiments, a first sample module adapter 130 is configured to communicatively couple a first configuration of sample module 120 to impedance bridge 140, a second sample module adapter 130 is configured to communicatively couple a second configuration of sample module 120 to impedance bridge 140, and so on. In this way, medical device 100 can utilize multiple different configurations of sample module 120. Various embodiments of sample module 120 and sample module adapter 130 are described below in conjunction with
Impedance bridge 140 can be an impedance load that controller 160 measures to determine an impedance of a circuit that includes impedance bridge 140, an amplifier (when present), and electrode array 126. For example, in some embodiments, when first electrode 121 and second electrode 122 of electrode array 126 contact a tissue sample on sample-receiving surface 125, controller 160 generates frequencies for a current conducted within the circuit that includes impedance bridge 140 and electrode array 126. In various embodiments, impedance bridge 140 further includes an amplifier (not shown) that is an analog interface amplifier for amplifying a supplied voltage and/or a return voltage while a current is conducted at various frequencies between impedance bridge 140 and the electrode array 126. It is noted that impedance bridge 140 and electrode array 126 form a circuit when a tissue sample contacts first electrode 121 and second electrode 122 of electrode array 126, sample module 120 is disposed in sample module adapter 130, and sample module adapter 130 is coupled to medical device 100. Digitizing circuitry 150 digitizes signals in such a circuit to enable operation of controller 160.
Controller 160 includes a processing unit 161 and a memory 162 and performs one or more operations to implement various embodiments described herein. For example, in some embodiments, controller 160 executes a program stored in memory 162 to conduct multiple specific electrical measurements on a tissue sample using first electrode 121 and second electrode 122 of electrode array 126. In some embodiments, controller 160 may receive instructions from a user via I/O devices 170 to perform the electrical measurements, such as one or more impedance measurements 163, using electrode array 126. In some embodiments, controller 160 may receive instructions from the user via I/O devices 170 to store data, such as data associated with one or more impedance measurements 163. In some embodiments, the stored data associated with impedance measurements 163 includes the measured electrical properties determined by the measurement circuit that includes impedance bridge 140 and electrode array 126. For example, in some embodiments, controller 160 stores the measured voltage and the measured current for an input signal at a specific operating frequency.
In some embodiments, controller 160 determines a determined tissue type 164 of a tissue sample contacting first electrode 121 and second electrode 122. In the embodiments, the determined tissue type is based on one or more impedance measurements 163 associated with the sample contacting first electrode 121 and second electrode 122. In various embodiments, controller 160 determines a determined tissue type 164 by comparing impedance measurements 163 with one or more characteristic impedance measurements associated with one or more tissue types. For example, and without limitation, based on the comparing, controller 160 can determine which tissue type is associated with characteristic impedance measurements that are closest to impedance measurements 163 of the sample tissue contacting first electrode 121 and second electrode 122.
In various embodiments, controller 160 can determine a Cole relaxation frequency of the tissue sample based on impedance measurements 163. Specifically, controller 160 computes the Cole relaxation frequency for the tissue sample based on the computed impedances corresponding to the operating frequency, where the Cole relaxation frequency for the tissue sample reflects the rate at which a cell membrane discharges a stored electrical charge. In the embodiments, Controller 160 compares the Cole relaxation frequency to one or more characteristic Cole relaxation frequencies of one or more tissue types. The Cole relaxation frequency for a particular tissue sample corresponds to a frequency associated with a greatest impedance measurement 163 included in the one or more impedance measurements 163 for that particular tissue sample. In various embodiments, the Cole relaxation frequency is a frequency of a maximum normalized impedance measurement of the tissue sample contacting first electrode 121 and second electrode 122.
Due to the contrasting electrical properties of malignant cells and non-malignant cells, malignant cells have a Cole relaxation frequency that is over one thousand times smaller than the Cole relaxation frequency of a non-malignant cell. Consequently, in some embodiments, based on a Cole relaxation frequency below a lower threshold frequency (e.g., 105 Hz), controller 160 can determine that the tissue sample contacting first electrode 121 and second electrode 122 is a non-tumor tissue type (also referred to as non-cancerous tissue). Similarly, in some embodiments, based on a Cole relaxation frequency above an upper threshold frequency, controller 160 can determine that the tissue sample contacting first electrode 121 and second electrode 122 is a tumor tissue type (also referred to as cancerous tissue). Further, for example and without limitation, based on a Cole relaxation frequency that is between the lower threshold frequency (e.g., of 500 kHz) and above the upper threshold frequency (e.g., of 1 MHz), controller 160 can determine that the tissue sample contacting first electrode 121 and second electrode 122 is a precancerous tissue.
In some embodiments, processing unit 161 can be a single central processing unit (CPU), or combination of processing units. Processing unit 161 may be any technically-feasible hardware unit capable of processing data and/or executing software code. In some embodiments, processing unit 161 receives instructions from a user via I/O devices 170 and/or from memory 162 and may execute such instructions. In some embodiments, processing unit 161 implements one or more techniques executed by controller 160. In some embodiments, memory 162 is configured to store data and/or software applications. Memory 162 may include a random access memory (RAM) module, hard disk, flash memory unit, or any other type of memory unit or combination thereof. Controller 160 and I/O units 130 are configured to read data from memory 162 and to write data to memory 162.
Input/output (I/O) devices 170 may include devices capable of receiving one or more inputs, including a keyboard, mouse, input tablet, camera, and/or three-dimensional (3D) scanner. In some embodiments, I/O devices 170 may also include devices capable of providing one or more outputs, such as a speaker, printer, or a display 171. Display 171 displays data generated by medical device 100. In an embodiment, display 171 displays one or more of the computed Cole relaxation frequency and/or a determined tissue type 164. In some embodiments, display 171 may refresh the data generated by medical device 100 while medical device 100 performs measurements on a particular tissue sample. I/O devices 170 may also include devices capable of both receiving inputs and providing outputs, such as a touchscreen and a universal serial bus (USB) port.
Compressive tissue sample holder 331, when installed over medallion electrode array 320 onto housing 334, presses medallion electrode array 320 against a tissue sample (not shown) that is disposed on a tissue sample-receiving surface 335 of sample module adapter 230. In the embodiment illustrated in
Returning to
In some embodiments, to enable medallion electrode array 320 to be arranged in any rotational orientation, medallion electrode array 320 is round in configuration. Further, the portion of first electrode 321 disposed on reverse surface 337 is radially displaced from the portion of second electrode 322 disposed on reverse surface 337. Thus, medallion electrode array 320 can be electrically connected to conductors included in compressive tissue sample holder 331 regardless of the rotational orientation of medallion electrode array 320. For example, in the embodiment illustrated in
In some embodiments, impedance measurements of a tissue sample are collected via a tab electrode. In such embodiments, a tab electrode is employed to electrically contact the tissue sample instead of a medallion electrode. One such embodiment is described below in conjunction with
In some embodiments, impedance measurements of a tissue sample are collected via an array of transparent electrodes disposed on an optically transparent substrate. In such embodiments, the optically transparent substrate can be employed as an microscope slide. One such embodiment is described below in conjunction with
In the embodiment illustrated in
As shown, a method 1000 begins at step 1002, where a biopsy sample is obtained from a region of patient anatomy, such as a target lesion. In some instances, the lesion is imaged so that the location of the target lesion can be determined. For example, in some instances, the region of patient anatomy can be imaged via X-ray, ultra-sound, and/or magnetic resonance imaging (MRI). The biopsy sample is then taken using an appropriate biopsy procedure, where the appropriate biopsy procedure may be determined based on the location of the target lesion and/or the general region of patient anatomy of concern. Examples of such biopsy procedures include needle biopsy, endoscopic biopsy, skin biopsy, bone marrow biopsy, surgical biopsy, and the like. Typically, a needle or hollow tube is employed to take a particular biopsy sample from the region of anatomy or target lesion.
In step 1004, the biopsy sample is placed onto sample-receiving surface 125 of a sample module 120. For example, in some instances, the biopsy sample, such as a biopsy core from a needle biopsy syringe, is flushed with saline onto tissue sample-receiving surface 335 of sample module adapter 230. Alternatively, the biopsy sample can be flushed onto sample-facing surface 636 of a tab electrode 600 or onto a transparent substrate 902.
In step 1006, the sample module 120 on which the biopsy core has been placed is coupled to an appropriate sample module adapter 130, such as sample module adapter 230 or sample module adapter 730. In some embodiments, a removable compressive tissue sample holder is first used to press an electrode array of sample module 120 against the biopsy sample disposed on the tissue sample-receiving surface 125 of sample module 120.
In step 1008, one or more impedance measurement(s) 163 of the biopsy sample are performed with medical device 100. As described previously, one or more impedance measurements 163, at one or more frequencies, are performed and recorded via controller 160, impedance bridge 140, and electrode array 126.
In step 1010, controller 160 determines a determined tissue type 164 for the biopsy sample based on the impedance measurement(s) 163 performed in step 1008. In some embodiments, the determined tissue type 164 is further determined based on comparing the Cole relaxation frequency of the biopsy sample to one or more characteristic Cole relaxation frequencies of one or more tissue types. In such embodiments, the comparison can be based on a single threshold frequency or on a lower threshold frequency and an upper threshold frequency.
In embodiments in which the comparison is based on a single threshold frequency, controller 160 determines that the determined tissue type 164 is non-cancerous when the Cole relaxation frequency of the biopsy sample is less than the single threshold frequency and cancerous when the Cole relaxation frequency of the biopsy sample is greater than the single threshold frequency. Alternatively, in embodiments in which the comparison is based on a lower threshold frequency and an upper threshold frequency, the controller determines that the determined tissue type 164 is non-cancerous when the Cole relaxation frequency of the biopsy sample is less than the lower threshold frequency, cancerous when the Cole relaxation frequency of the biopsy sample is greater than the upper threshold frequency, and pre-cancerous when the Cole relaxation frequency of the biopsy sample is both greater than the lower threshold frequency and less than the upper threshold frequency. It is noted that threshold frequencies generally vary based on a particular tissue type, and can be determined empirically. For example, the threshold frequencies for pancreatic tissue can be significantly different that the threshold frequencies for bone marrow tissue, skin tissue, lung tissue, and the like.
In step 1012, controller 160 causes one or more indicators of determined tissue type 164 to be displayed. For example, in some embodiments, controller 160 causes graphical representation 223 of results for the biopsy sample to be displayed by display 171. Alternatively or additionally, in some embodiments, controller 160 causes textual results 224 of results for the biopsy sample to be displayed by display 171.
In sum, embodiments described herein enable the determination of a tissue type for a tissue sample. Based on ex vivo impedance measurements performed on the tissue sample, a medical device can determine whether the tissue sample is cancerous, non-cancerous, or pre-cancerous. An impedance bridge is employed to perform the impedance measurements without altering or consuming a the tissue sample, and an electrode array of the medical device is configured with interdigitated electrode elements to facilitate electrical contact with the tissue sample during such measurements.
At least one technical advantage of the disclosed design and techniques relative to the prior art is that the disclosed design and techniques provide immediate, real-time feedback to a clinician who is performing a surgical biopsy. Consequently, when a tissue sample is determined to be non-diagnostic via the disclosed design and techniques, the clinician can immediately take one or more additional tissue samples, thereby avoiding the long delays in diagnosing non-diagnostic tissue samples that are typical with conventional approaches. In addition, because the disclosed design and techniques provide feedback to physicians within seconds, the workflow of a surgical biopsy procedure is not substantially impacted, and the duration of the surgical biopsy procedure is not significantly extended. A further technical advantage of the disclosed techniques is that tissue samples taken by a clinician are not altered; therefore, the reliability of subsequent pathological analyses are not adversely impacted. These technical advantages provide one or more technological advancements over prior art approaches.
Any and all combinations of any of the claim elements recited in any of the claims and/or any elements described in this application, in any fashion, fall within the contemplated scope of the present invention and protection.
The descriptions of the various embodiments have been presented for purposes of illustration, but are not intended to be exhaustive or limited to the embodiments disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments.
Aspects of the present embodiments may be embodied as a system, method or computer program product. Accordingly, aspects of the present disclosure may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, micro-code, etc.) or an embodiment combining software and hardware aspects that may all generally be referred to herein as a “module,” a “system,” or a “computer.” In addition, any hardware and/or software technique, process, function, component, engine, module, or system described in the present disclosure may be implemented as a circuit or set of circuits. Furthermore, aspects of the present disclosure may take the form of a computer program product embodied in one or more computer readable medium(s) having computer readable program code embodied thereon.
Any combination of one or more computer readable medium(s) may be utilized. The computer readable medium may be a computer readable signal medium or a computer readable storage medium. A computer readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing. More specific examples (a non-exhaustive list) of the computer readable storage medium would include the following: an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing. In the context of this document, a computer readable storage medium may be any tangible medium that can contain, or store a program for use by or in connection with an instruction execution system, apparatus, or device.
Aspects of the present disclosure are described above with reference to flowchart illustrations and/or block diagrams of methods, apparatus (systems) and computer program products according to embodiments of the disclosure. It will be understood that each block of the flowchart illustrations and/or block diagrams, and combinations of blocks in the flowchart illustrations and/or block diagrams, can be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine. The instructions, when executed via the processor of the computer or other programmable data processing apparatus, enable the implementation of the functions/acts specified in the flowchart and/or block diagram block or blocks. Such processors may be, without limitation, general purpose processors, special-purpose processors, application-specific processors, or field-programmable gate arrays.
The flowchart and block diagrams in the figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods and computer program products according to various embodiments of the present disclosure. In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of code, which comprises one or more executable instructions for implementing the specified logical function(s). It should also be noted that, in some alternative implementations, the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or acts, or combinations of special purpose hardware and computer instructions.
While the preceding is directed to embodiments of the present disclosure, other and further embodiments of the disclosure may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow.
The present application claims the benefit of U.S. Provisional Patent Application No. 63/379,613, filed Oct. 14, 2022. The subject matter of this related application is hereby incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 63379613 | Oct 2022 | US |
