Tissue marker detection system and method using ultrasound and tissue markers

Abstract

Ultrasound systems and methods transmit broadband ultrasound waves through a probe to excite and detect markers in body tissue (e.g., breast, lung). Returned ultrasound energy (narrowband) detected by the probe is processed to distinguish the marker's response from other detected ultrasound waves. This processing is fast enough to accommodate typical handheld probe movement while providing accurate localization. Processing may include RF filtering and mixing, demodulation, and target detection via spatial or "image" processing based on the known geometry of the marker and its response signature. Target detection may include sigma mapping with frame-to-frame comparison and target best-fit processing to isolate the blob that best matches a set of target spatial criteria. Optionally, nonlinearity is introduced into the ultrasound transmission and used in distinguishing the marker's response. The marker can be suspended for movement within a hydrated gel.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Patent Application No. 63 / 441,558, filed January 27, 2023, and U.S. Patent Application No. 63 / 525,280, filed July 6, 2023, both of which are incorporated by reference herein in their entireties.

[0002] The present disclosure relates generally to markers (e.g., tissue markers) and detection of markers in body tissue, and more particularly to markers with enhanced detectability via ultrasound (e.g., color Doppler ultrasound), as well as systems and methods using ultrasound to detect markers that may facilitate detection of the margins of body tissue (e.g., abnormal body tissue) to be monitored, biopsied, excised, or cut, for example, during a surgical procedure. [Background technology]

[0003] <Description of Related Art> Various types of markers are used to mark body tissues that are monitored over time, biopsied, excised, or cut (or ablated). Some markers may enable or enhance visual detection, for example, by a surgeon, during a surgical procedure. Some markers allow for detection via various types of energy-emitting imaging modalities, such as ultrasound imaging, radiological imaging such as X-ray imaging, computed tomography (CT) imaging, computed axial tomography (CAT) imaging, or magnetic resonance imaging (MRI). These different imaging modalities are often used in different scenarios by different clinicians or technicians, and markers that are detectable under various visual detection or imaging modalities typically require different physical properties to be detectable. DISCLOSURE OF THE INVENTION [Problem to be solved by the invention]

[0004] Some markers may be permanent, while others may be absorbable by the body over a period of time, for example, it may be useful to mark a portion of body tissue for subsequent evaluation or detection over a significant period of time (e.g., months, years). [Means for solving the problem]

[0005] The applicant has developed a multi-modal marker that is detectable via ultrasound and detectable via additional imaging modalities (e.g., X-ray, MRI and / or other imaging techniques), optionally absorbable over time, and may last for an extended period of time (e.g., may last for approximately 9 months).

[0006] Markers for use with body tissues may take various forms and may include multiple ultrasound-reflecting elements and one or more gels (e.g., hydrogels) connecting the ultrasound-reflecting elements. The ultrasound-reflecting elements may take the form of, for example, porous or mesoporous particles, or porous or mesoporous hollow shells. The cavities and / or pores of the ultrasound-reflecting elements (e.g., hollow shells, porous or mesoporous particles) may be filled with a fluid, e.g., a gas such as air, a liquid, or a combination of a gas and a liquid (e.g., steam), and may advantageously optionally be devoid of perfluorocarbons. The ultrasound-reflecting elements may be coated, for example, with a hydrophobic coating to at least temporarily seal the pores to prevent or delay the ingress of liquid into the internal cavities of the ultrasound-reflecting elements (e.g., hollow shells, porous or mesoporous particles).

[0007] The ultrasound reflective element can include or consist of one or more forms of silica. The gel (e.g., hydrogel) can be a natural gel, such as gelatin, or an artificial gel, such as polyethylene glycol (PEG), or the marker can be composed of both natural and artificial gels (e.g., natural and artificial hydrogels). The gel may be partially or fully crosslinked. The gel (e.g., hydrogel) can be designed to be absorbed by the body over a period of time, or it can be non-absorbable.

[0008] In addition to being detectable via ultrasound, the marker may optionally include a contrast element or "contrast agent" that allows the marker to be detected via one or more imaging modalities. For example, the marker may include one or more radiopaque materials (e.g., metals such as gold, platinum, tantalum, bismuth, barium, etc.) to enable the marker to be detected via X-ray imaging. For example, the marker may include a metal element in the form of a clip (e.g., a metal wire having a defined shape, e.g., a helically wound metal wire), a strand or coil, or a plurality of metal particles. For example, the marker may also include one or more MRI imaging contrast agents (e.g., a gadolinium-containing compound such as gadolinium-DTPA, ferrous gluconate, ferrous sulfate, etc.) to enable the marker to be detected via MRI imaging. For example, the marker may also include one or more dyes (e.g., a fluorescent dye, methylene blue) to enable the marker to be more easily visually detected.

[0009] There is a need for improved imaging techniques that do not use ionizing radiation, such as improved ultrasound imaging techniques that can enhance the detection of markers in body tissue and / or the detection of the margins of particular body tissue (e.g., abnormal body tissue, e.g., tumors, or body tissue suspected to be abnormal) marked with implanted markers. Such could advantageously enable marker localization in surgical scenarios where ionizing radiation sources are not readily available, or may be undesirable or otherwise inconvenient to use.

[0010] There is also a need for improved markers, for example tissue markers that are more easily detectable in body tissues.

[0011] The present disclosure generally relates to the detection of markers in body tissue, and further relates to systems and methods that may use ultrasound processing to facilitate, for example, more accurate detection of tissue to be monitored, biopsied, excised, or cut than is possible using conventional approaches. The systems and methods advantageously do not require ionizing radiation to perform marker localization in at least some settings or implementations. The systems and methods may be particularly suitable for use in surgical procedures, for example, by surgeons or others who are not professional or dedicated medical imaging technicians or professional or dedicated ultrasound technicians. Thus, it would be particularly advantageous if operation of the systems and methods were simplified and, for example, did not require manual adjustment of setup or input parameters by an operator (e.g., a surgeon). Furthermore, it would be particularly advantageous if operation of the systems and methods accommodated the hand movements of an operator holding a probe (e.g., an ultrasound probe), who is typically not a skilled or dedicated ultrasound technician, for example, by accommodating imprecise and / or rapid or uneven movements (e.g., varying speeds) of the probe. It would be even more particularly advantageous if the system's operation provides accurate localization in at least a two-dimensional area, preferably a three-dimensional volume, using, for example, visual and / or audible indications or warnings. It would also be even more particularly advantageous if the system provides accurate results with few or no false results (e.g., false detections or false warnings; missing a marker when one is present). User feedback may be provided visually (e.g., a representation of a marker or crosshairs against an image of the anatomy) and / or audibly (e.g., an audible warning when the probe moves towards or away from a marker in one, two, or even three dimensions).

[0012] The present disclosure also generally relates to markers (e.g., tissue markers) that have physical properties that make the markers more easily identifiable via ultrasound (e.g., color Doppler ultrasound) when the markers are implanted in bodily tissue. Such markers can include a gel body having a plurality of ultrasound-reflecting elements (e.g., porous or mesoporous particles; porous or mesoporous hollow shells) held in suspension within the gel body. The ultrasound-reflecting elements may be dispersed throughout the gel body, for example, in a colloidal dispersion or suspension.

[0013] The gel body may take the form of a hydrogel (e.g., a natural hydrogel, an artificial hydrogel, or a combination of natural and artificial hydrogels). The gel body may be fully or partially crosslinked, so long as, when the gel body is hydrated, the ultrasound reflective elements are free to move (e.g., sway or vibrate, or preferably randomly) in at least one dimension (e.g., along at least one axis, preferably along two or more axes) to a degree or distance sufficient to enhance any scattered return (e.g., backscatter) from the ultrasound reflective elements in response to ultrasound interrogation of the marker, preferably with (or using) variations in the velocity of the ultrasound reflective elements and / or amalgamation or clusters of the ultrasound reflective elements.

[0014] The ultrasound reflective element typically has an irregular surface that provides scattering (e.g., backscatter) in response to ultrasonic interrogation of the marker. The ultrasound reflective element typically retains a fluid (i.e., a gas, liquid, or a combination of gas and liquid, but typically a gas, e.g., air or an inert gas), which enhances backscatter in response to ultrasonic interrogation of the marker. The ultrasound reflective element typically includes a hydrophobic coating (e.g., silicone) that prevents liquid from entering the pores, cavities, or interior of the ultrasound reflective element over an extended period of time (e.g., 3 months, 9 months, 18 months, or longer). Such advantageously prevents the ultrasound reflective element from "wetting out" (which would reduce or even eliminate detectable scattering).

[0015] The gel body may be dehydrated or freeze-dried before being implanted into body tissue, and then hydrates over a period of time as fluid (e.g., water) is absorbed from the body tissue. The gel body also provides a framework for bio-adhesion through the natural healing process of the body tissue into which the marker is implanted. As such, it may secure the marker in place within the body tissue without the use of glues or adhesives.

[0016] Various of these described physical structures or physical properties of the markers provide or enhance scattering (e.g., backscatter) of ultrasound from the markers, and in particular contribute to variations in the position and / or velocity of ultrasound-reflecting elements, either individual or in agglomerations or clusters, resulting in a wide velocity spectrum that significantly contributes to detectability using color Doppler ultrasound techniques.

[0017] The ultrasound system (e.g., hardware, software, firmware) uses excitation and detection algorithms to identify responses from markers and provide intuitive indications (distinct visual indications that do not themselves represent bodily tissue, distinctive auditory alerts). Such systems represent a very different approach compared to commercial off-the-shelf ultrasound systems. While a trained clinician can locate markers within tissue using images from conventional color Doppler, the approach described herein allows for much faster acquisition and a hands-free, zero-setup user experience. In contrast, conventional ultrasound requires a trained clinician to adjust settings on the ultrasound machine. Conventional ultrasound is an interpretive visual activity, requiring a trained clinician to visually interpret the displayed ultrasound image. In the approach described herein, the ultrasound system alerts the clinician in real time whether a marker has been found and where that marker is located within the tissue. Thus, the clinician, who must attempt to interpret anatomical structures within an ultrasound image, receives what can be characterized as a binary answer (e.g., when a marker is located, a visually distinct and audible indication of its presence is presented), along with automatic ranging (e.g., distance and direction relative to the current location). The approach described herein does not require knobs or clinician-adjusted settings, but instead provides quick and simple detection through intuitive operation without interrupting the normal workflow of the operating room. This is particularly important in surgical environments with an anesthetized patient, in a sterile field, and when the clinician is likely not experienced using ultrasound as a typical ultrasound technician, but is a surgeon engaged in other aspects of the surgical procedure.

[0018] Unlike conventional approaches where ultrasound energy is focused on a specific region of interest (ROI), in the approach described herein, the transmit beam model spreads the energy throughout the entire interrogation space. The GPU algorithm advantageously implements parallel processing signal path analysis in the receive beam model to distinguish responses from markers from all other detected signals and noise.

[0019] A detection and imaging system is designed to help clinicians (e.g., surgeons) locate implanted tissue markers (e.g., View Point Medical's OneMark™ markers). The system is used to scan and localize implanted markers within body tissue (e.g., breast tissue, lung tissue). The system transmits pulsed ultrasound energy to excite the marker and then compares changes in motion between sets of pulses from the received ultrasound energy (e.g., a return signal or series of return signals that may constitute scattered or backscattered returns of ultrasound energy from the marker or portions of the marker). The pulses induce higher variations in energy levels where the marker is located compared to unmarked areas. The system highlights the marker location on a display screen (e.g., a liquid crystal display (LCD)), for example, using a color map overlay on a low-resolution grayscale representation of the anatomical background. The system may additionally or alternatively indicate the location of the marker using additional audio and visual feedback, for example as an XY crosshair centered over the marker in a low-resolution grayscale representation of the anatomical background.

[0020] Typically, surgeons locate a site-center marker and resect around the marker to reasonably confirm that they have performed the correct resection. This system supports the current standard of care for lesion localization and provides more visual information than currently used wire-free localization devices that do not visually display markers. The systems and methods described herein can generate localization information that advantageously represents the center of mass of the marker (e.g., visually represented by crosshairs), as opposed to the sound or wire center or a tag, and may prove particularly uniquely advantageous for real-time image centering of the marker in a surgical setting.

[0021] The scanning process applies a non-diagnostic, custom, ultrasound-based method to excite the markers and provide the clinician (e.g., surgeon) with a real-time image of the marker location from the skin surface within the wound during ablation. Unlike traditional diagnostic ultrasound imaging, the system does not necessarily provide quantitative information about anything scanned other than the markers the system is designed to detect. Unlike ultrasound systems intended to show all of the tissue's structural features, the OneMark™ system optionally, but preferably, does not offer a diagnostic ultrasound mode, is not intended as a tool for qualitative tissue analysis, and does not offer adjustment controls like diagnostic tools do. The system may be used to image marker locations to provide information to assist with clinical localization. The system advantageously requires little setup and is designed to be used by surgeons who are not dedicated sonographers and who do not typically operate ultrasound equipment in their daily work. It automates the marker imaging process and eliminates buttons and / or keys or keyboards, designed for maximum ease of use and better suited for sterile field applications. The system also advantageously supports rapid marker detection to efficiently assist clinicians treating patients under anesthesia.

[0022] In contrast to most ultrasound systems used for diagnosis, which attempt to focus the transmitted ultrasound energy at a point of interest, the currently described ultrasound systems and methods in at least one mode spread the transmitted broadband ultrasound energy throughout the entire region of interest (e.g., the entire breast, the entire lung). Thus, rather than attempting to improve resolution as is done in diagnostic ultrasound, the ultrasound systems and methods described herein attempt to achieve high, or even optimal, power coupling with the marker. Ultrasound waves may be transmitted as ensembles of pulses along various axes, angles, or beams, each associated with a respective piezoelectric element, crystal, or transducer of the ultrasound probe. In contrast to most ultrasound systems used for color Doppler, which use relatively low frame rates with a relatively high number of pulses per ensemble, the currently described ultrasound systems and methods typically use relatively high frame rates with a relatively low number of pulses per ensemble (e.g., 3, 4, 5), and also typically use a relatively low depth of focus (e.g., 2) to fully achieve speeds sufficient to accommodate expected hand movements of the ultrasound probe. The ultrasound systems and methods described herein may, for example, use ensembles of up to five pulses per beam at two different focal depths when operating in color Doppler mode, and may, for example, use ensembles of up to four pulses per beam when operating in B-mode.

[0023] The presently described ultrasound systems and methods, for example, induce movement of echogenic materials (e.g., fluid-trapped silica particles) in hydrogels using transmitted pulsed ultrasound to vibrate the echogenic material at a resonant or beat frequency. The presently described ultrasound systems and methods use this vibration to identify or locate markers, for example, by examining received ultrasound (e.g., a return signal or series of return signals, which may constitute scattered or backscattered return of ultrasound energy from a marker or portion of a marker) for relatively large frame-to-frame movements compared to background features, which generally indicate a vibrating marker. Thus, the system attempts to impart or "pump" enough energy to the echogenic material to induce vibration. Such vibrations can appear as a sparkling or twinkling effect in color modes of ultrasound imaging. Increasing the amount of energy applied may include increasing the power or amplitude (e.g., voltage) of the pulses, increasing the number of pulses, increasing the pulse repetition frequency, and / or increasing the number of piezoelectric elements, crystals, or transducers in the head of the ultrasound probe. While the pulse repetition should be close enough to keep the echogenic material in vibration, it may be desirable to have some gaps between ensembles of pulses, for example, to provide some headroom within the ultrasound probe.

[0024] In particular, the more pulses in an ensemble, the more time it takes to transmit, receive, and process the ultrasound. This, along with the reliance on identifying the marker's response in multiple consecutive frames to accurately determine the marker's location and the fact that ultrasound probes are typically handheld and subject to movement, imposes constraints on technical operational aspects, including the transmit model, frame rate, and receive signal processing chain. In addition, while a relatively large amplitude (e.g., voltage) of the transmitted ultrasound pulse may facilitate detection of the marker's response, several practical considerations may impose constraints on such. For example, the thermal limitations of the piezoelectric element, crystal, or transducer, or the ultrasound probe head, may limit the amplitude of the transmitted ultrasound pulse that can be used.

[0025] The presently described ultrasound systems and methods use a receive signal processing chain to process a return signal or series of return signals, which may constitute scattered or backscattered returns of ultrasound energy from a marker or portion of a marker. The receive signal processing chain may include one, more, or all of RF filtering and mixing, demodulation and envelope detection, and target detection via spatial or "image" processing based on the known geometry of the marker and its response signature. Target detection may include sigma mapping with frame-to-frame comparison and target best fit processing to isolate the blob that best matches a set of target spatial criteria. The processing is fast enough to accommodate the movement of a typical handheld probe while providing accurate localization.

[0026] In some implementations, a system (e.g., an ultrasound system) advantageously injects nonlinearity into the drive signal to create nonlinearity in the ultrasound transmission or interrogation signal (or interrogation signal). The nonlinearity can create a nonlinear response or return from the tissue marker (e.g., from the echogenic portion of the tissue marker), thus facilitating detection (e.g., match filtering) of the tissue marker by the ultrasound system. The nonlinearity may preferably take the form of a change in the amplitude (e.g., voltage) of the ultrasound transmission or interrogation signal. Additionally or alternatively, the nonlinearity may be introduced by varying the frequency or phase of the ultrasound transmission or interrogation signal from a nominal frequency or phase. For example, a variation may be introduced in the base or fundamental frequency of the outgoing ultrasound transmission and / or a variation may be introduced in the pulse repetition frequency of the outgoing ultrasound transmission. The nonlinearity may be periodic, form or follow a defined pattern, or be pseudorandom or random.

[0027] In some implementations, systems (e.g., ultrasound systems) and methods advantageously introduce a magnetic field into body tissue. Such may be suitable for enhancing detection of markers in some body tissues (e.g., lung tissue with a large amount of air) and are useful with suitable markers (e.g., tissue markers including ferrous metal and / or ferrous oxide). The system may generate the magnetic field by passing a current through an electrical conductor (e.g., an antenna, a coil antenna, a closed-loop antenna). The conductor may be carried by or otherwise part of an ultrasound probe, for example. The magnetic field may be periodic, form or follow a defined pattern, or may be pseudorandom or random. The magnetic field may oscillate, which may cause the marker or a portion thereof to vibrate or rock, for example, at a resonant frequency, or generate a beat frequency. An outgoing ultrasound transmission may be superimposed on the magnetic field. In some implementations, the ultrasound waves (e.g., a return signal or series of return signals) received by the receiving section may be synchronized with the transmission of the magnetic field. The use of a magnetic field may advantageously facilitate detection of ultrasound returns from the tissue marker (e.g., from the echogenic portion of the tissue marker). [Brief explanation of the drawings]

[0028] In the drawings, identical reference numbers indicate similar elements or acts. The sizes and relative positions of elements in the drawings are not necessarily drawn to scale. For example, the shapes and angles of various elements are not drawn to scale, and some of these elements have been appropriately enlarged and positioned from time to time to improve drawing readability. Furthermore, the specific shapes of elements shown are not necessarily intended to convey any information regarding the actual shape of the particular elements, but have been selected merely for clarity.

[0029] [Figure 1A]FIG. 1A is an isometric view of a marker for marking body tissue and a distal portion of an instrument selectively operable to implant the marker at a desired location within the body tissue, according to one illustrated embodiment, the marker including a persistent (e.g., long-term) portion and two other fast-dissolving portions.

[0030] [Figure 1B] FIG. 1B is an isometric view of a marker according to one illustrated embodiment, which can take the form of, for example, a gel (e.g., hydrogel) carrier, multiple ultrasound-reflecting elements, a clip, strand, or coil detectable by X-ray imaging, and optionally a long-lasting (long-term) portion (FIG. 1A) including a contrast agent for enhanced detection in imaging modalities other than ultrasound, with an enlarged detail view detailing one of multiple aggregations or clusters of ultrasound-reflecting elements.

[0031] [Figure 2] FIG. 2 is a schematic diagram of an ultrasound system according to at least one illustrated embodiment, in which an ultrasound transducer is positioned relative to a marker that is ultrasound reflective and typically implanted in body tissue, and the ultrasound imaging system is operable to cause transmission of broadband ultrasound signals into the body tissue, process the received ultrasound energy to discern or identify responses from the marker, and provide appropriate visual and / or audible indications of the presence and / or location of the marker.

[0032] [Figure 3] FIG. 3 is a block diagram illustrating an exemplary architecture of an ultrasound system, according to at least one illustrated embodiment.

[0033] [Figure 4] FIG. 4 is a block diagram illustrating an exemplary receive signal chain of an ultrasound system in accordance with at least one illustrated embodiment, and particularly detailing the receive signal processing chain.

[0034] [Figure 5A-C] 5A, 5B, and 5C illustrate a method of processing received ultrasound energy to identify responses from markers and provide visual and / or audible indications of the presence and / or location of the markers, according to at least one illustrated embodiment, and in particular detail an implementation of RF demodulation.

[0035] [Figure 6A-B] 6A and 6B illustrate a method for processing received ultrasound energy to identify responses from markers and provide visual and / or audible indications of the presence and / or location of the markers, in accordance with at least one illustrated embodiment, and particularly detail an implementation of sigma mapping.

[0036] [Figure 7A-D] 7A-7D illustrate a method for processing received ultrasonic energy to identify responses from markers and provide visual and / or audible indications of the presence and / or location of the markers, in accordance with at least one illustrated embodiment, and in particular detail a target detection implementation. DETAILED DESCRIPTION OF THE INVENTION

[0037] <Detailed explanation> To provide an appreciation of various embodiments, certain details of the disclosure are described below. However, those skilled in the art will readily appreciate that the present invention may be practiced without one or more of these specific details, or with other methods, components, or materials. In other instances, well-known structures related to microcontrollers, piezoelectric elements, crystals or transducers, power supplies such as DC / DC, computing systems, and communication networks (e.g., cellular, packet-switched), and other communication channels have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments.

[0038] Unless reason otherwise requires in this specification and claims, the term "comprise" and its derivatives (such as "comprises" and "comprising") are to be considered to have an open-ended, inclusive meaning, i.e., "including, but not limited to."

[0039] Throughout this specification, a reference to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least one embodiment. Thus, all appearances of the phrase "in one embodiment" or "in an embodiment" herein are not necessarily referring to the same embodiment. Furthermore, particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0040] As used in this specification and the appended claims, the singular forms (a, an, and the) include plural referents unless the content clearly dictates otherwise. Also, the term "or" is generally used in its sense to include "and / or" unless the content clearly dictates otherwise.

[0041] As used herein and in the appended claims, the terms left, right, above, and below are used to refer to four directions along two perpendicular axes with respect to a location, position, or cell in a two-dimensional array of data layouts. For example, the terms left and right can refer to the nearest neighbor in a row on each side of a specified location, position, or cell in the array. Similarly, the terms up and down can refer to the nearest neighbor in a column spaced relatively above and relatively below a specified location, position, or cell in the array. Note that the terms left, right, above, and below are used for convenience and in a relative sense, not an absolute sense. Thus, the orientation of an array or arrangement of data can be changed, for example, rotated 90 degrees, 180 degrees, or mirrored.

[0042] The title and abstract are for convenience only and do not represent the scope of the invention or imply embodiments.

[0043] In particular, the systems and methods described herein may use ultrasound to determine the presence or absence and / or location of tissue markers in bodily tissue, which may be used, for example, to more precisely define the margins of abnormal or suspicious tissue (e.g., tumors) in bodily tissue.

[0044] FIG. 1A shows a marker 100 for marking body tissue and a distal portion of an instrument 101 selectively operable to implant the marker 100 or a portion thereof at a desired location within the body tissue, according to one illustrated embodiment.

[0045] The distal portion of the instrument 101 is shown in cross section to better illustrate the marker 100. The instrument 101 may take the form of an applicator, and the distal portion of the instrument 101 may take the form of a needle or similar structure having a lumen 101a into which the marker 100 is loaded and / or through which the marker 100 passes during use. To better illustrate the outer periphery of the marker 100, the marker 100 is shown offset (e.g., radially inward) from the inner wall 101b defining the lumen 101a, although typically the marker 100 will be closely received by or even contact the inner wall defining the lumen 101a. The distal portion of the instrument 101 has an opening 101c at its distal end. The distal portion is shown as having a pointed or sharp end, for example, for piercing or cutting body tissue.

[0046] 1A, the marker 100 comprises a long-lasting (e.g., long-term) portion 100a and two other rapidly dissolving portions 100b, 100c. In some implementations, one or both of the two other rapidly dissolving portions 100b, 100c may be optional and, therefore, may be omitted in some implementations.

[0047] The persistent portion 100a includes a gel body 104a, a plurality of ultrasound reflective elements 102a, 102b (only two of which are shown) that are detectable using ultrasound (e.g., detectable using color Doppler ultrasound), and one or more detectable objects 106 that are detectable using an imaging modality other than ultrasound. The ultrasound reflective elements 102a, 102b can take the form of, for example, porous or mesoporous hollow shells (as shown in FIG. 1A) and / or porous or mesoporous particles (as shown in FIG. 1B), which are described in more detail herein. A porous or mesoporous hollow shell, at least in some implementations, is distinguishable from a porous or mesoporous particle because, unlike a shell which includes at least a single primary cavity to which two or more, or typically all, pores are fluidly connected, a porous or mesoporous particle does not include a single primary interior cavity to which two or more, or typically all, pores connect (either between the exterior of the shell and the single primary interior cavity or its interior, or a hermetic coating (which does not provide a fluid communication path to its interior other than a hydrophobic coating). The detectable object 106 may, for example, take the form of a clip or strand or coil (e.g., metal) that is detectable using X-ray imaging, as described in more detail herein.

[0048] The gel body 104a can take the form of, for example, a hydrogel that is partially or fully crosslinked to enhance longevity when implanted in bodily tissue, thereby enabling detection via ultrasound and other imaging modalities throughout diagnostic and therapeutic procedures. The partially or fully crosslinked gel body 104a can also advantageously promote bioadhesion between the marker 100 and the bodily tissue into which it is implanted through the wound healing process. For example, the gel body 104a provides a fibrosis scaffolding that promotes bioadhesion without adhesives or glues. For example, the polymer combination of the gel body 104a is designed to facilitate minimal penetration of natural fibrosis healing.

[0049] The first rapidly dissolving portion 100b (the relatively inner portion adjacent to the persistent portion 100a) of the two other rapidly dissolving portions 100b, 100c may similarly include a gel body 104b and multiple ultrasound reflecting elements 102c (only one of which is extended). The gel body 104b of the first rapidly dissolving portion 100b may be polyethylene glycol (PEG) and is generally not cross-linked or not highly cross-linked, allowing for rapid hydration and therefore rapid activation of its ultrasound reflecting elements 102c. This provides a rapid response to ultrasound, assisting clinicians during initial implantation of the marker 100. The first rapidly dissolving portion 100b may dissolve after serving its purpose of providing an ultrasound response (e.g., backscatter) during implantation.

[0050] The second quickly-dissolving portion 100c (the outermost portion) of the two other quickly-dissolving portions 100b, 100c includes a gel body 104c and typically omits an ultrasound-reflecting element. A portion of the gel body 104c of the second quickly-dissolving portion 100c extends slightly outward from the opening 101c at the distal end of the lumen 101a of the device 101. The portion of the gel body 104c of the second quickly-dissolving portion 100c that extends slightly outward from the opening 101c has a bulbous end 104d for retaining the remainder of the marker 100 within the lumen 101a. The gel body 104c of the second quickly-dissolving portion 100c may be composed of PEG, which is generally not cross-linked or not highly cross-linked, allowing for rapid hydration and rapid dissolution after fulfilling its function of retaining the marker 100 within the lumen 101a of the device 101.

[0051] As best seen in the enlarged view, each of the ultrasound reflective elements 102a, 102b, 102c has one or more pores 108 (e.g., mesoporous) and contains a fluid 110 (e.g., air or other gas). Each of the ultrasound reflective elements 102a, 102b, 102c also includes a coating, such as a hydrophobic coating 112, that seals the pores 108 or the interior of the ultrasound reflective element 102a, 102b to prevent the ingress of liquids (e.g., water) while implanted in body tissue. The hydrophobic coating 112 may be made of or include, for example, silicone.

[0052] The ultrasound reflective elements 102a, 102b, and 102c can include or consist of silica. When implemented as a porous shell, the ultrasound reflective elements 102a, 102b, and 102c can be formed, for example, by deposition on a template and subsequent removal of the template (e.g., by calcination). One exemplary process for forming the ultrasound reflective elements 102a, 102b, and 102c as porous hollow shells begins with a styrene template in solution. TMOS and DETA are added, and the silica is plated onto the templates. The styrene template is then removed by calcination, and the resulting porous hollow shells are washed and coated with silane. The resulting porous hollow shells are then dried. Some or all of the resulting porous hollow shells are then tested to ensure they respond to ultrasound. The resulting porous hollow shells are then ready to be added to a hydrogel to construct the marker 100. The ultrasound reflecting elements 102a, 102b, 102c may have, for example, an overall size or dimension of about 2 mμ and a wall thickness of about 30 nm.

[0053] The ultrasound reflective elements 102a, 102b, 102c may alternatively comprise titanium dioxide (TiO2) having the same or similar overall structure (e.g., dimensions including pores, cavities, surface roughness, overall size or dimensions (e.g., 2 mμ), shape, and wall thickness (e.g., 30 nm)), but tend to have higher toxicity and would likely require separate U.S. Food and Drug Administration (FDA) approval. Other materials having the same overall structure, particularly inert materials that remain in the body for relatively long periods of time (e.g., 9 months, 18 months) without adverse effects and are otherwise compatible with long-term in vivo use and do not require separate FDA approval, may be viable candidates for the ultrasound reflective elements 102a, 102b, 102c.

[0054] Typically, the ultrasound reflective elements 102a, 102b, 102c tend to aggregate or cluster within the gel bodies 104a, 104b, for example, as shown and described with reference to FIG. 1B below.

[0055] The cross-linked gel body 104a of the persistent portion 100a allows for precise implantation and retention within the target tissue. The multiple ultrasound reflective elements 102a, 102b provide a unique response to ultrasound. The clip, strand, or coil (e.g., metal) 106 is detectable via x-ray imaging or potentially some other imaging modality. The shape of the clip, strand, or coil (e.g., metal) 106 can vary from persistent portion 100a to persistent portion 100a of the marker 100, allowing two or more different persistent portions 100a to be easily distinguished. As described above, the hydrophobic coating 112 seals the fluid 110 within the pores 108 of the ultrasound reflective elements 102a, 102b, 102c. The hydrophobic coating of the ultrasound-reflective elements 102a, 102b of the permanent portion 100a of the marker 100 is selected to seal the pores 108 for extended periods (e.g., 9 months, 18 months) while implanted in body tissue and thus hydrated by bodily fluids. The relatively inner, first, fast-dissolving portion 100b (with a porous shell) facilitates implantation because the cross-linked gel body 104a of the permanent portion 100a does not hydrate quickly enough to be visible via ultrasound during implantation. The relatively outermost, fast-dissolving portion 100b (without a porous shell) acts as a plug.

[0056] The ultrasound-reflecting elements 102a, 102b of the permanent portion 100a of the marker 100 are the primary source of ultrasound response. The ultrasound-reflecting elements 102a, 102b provide a basic scattering surface, with reflection enhanced by their porosity, with fluid 110 sealed within pores 108 via a hydrophobic coating 112. The surface roughness and wall thickness of the ultrasound-reflecting elements 102a, 102b, 102c can affect their response to ultrasound (e.g., backscatter). The shell structure and its mesoporosity are controlled by chemical and chemical processes, for example, through the deposition of silica flakes onto a template and subsequent calcination, which removes the template and forms cavities within the ultrasound-reflecting elements 102a, 102b, 102c. The mesoporous nature allows sound energy to enter the cavity or cavities of the ultrasound reflective elements 102a, 102b, 102c, e.g., into trapped air bubbles within the cavity or cavities, inducing or enhancing a type of scattering that facilitates detection by Doppler ultrasound. The overall size of the ultrasound reflective elements 102a, 102b, 102c and / or the overall size of the agglomerates of ultrasound reflective elements 102a, 102b, 102c can shift the spectrum of performance. The hydrophobic coating 112 seals the pores 108 and prevents fluid from entering the ultrasound reflective elements 102a, 102b, 102c, preventing them from "wetting out" and otherwise reducing the signal-to-noise (SNR) ratio of the ultrasound response. The ultrasound-reflecting elements 102a, 102b, and 102c generate a B-mode response in ultrasound imaging, which is a compound effect because color mode is an overlay on the B-mode. The B-mode signal sends out groups of B-mode imaging data, which are then interpreted as color Doppler images using color Doppler techniques. This structure, particularly the structure suspended in the gel matrix, allows movement in response to ultrasound energy and advantageously provides a wide range of harmonics detectable via color Doppler ultrasound. The amount of ultrasound-reflecting elements 102a, 102b, and 102c required to enable detection is very small.

[0057] An exemplary process for forming the marker 100 includes preparing (or cooking) a gel (e.g., a hydrogel component). The ultrasound-reflecting element may be coated with a hydrophobic polymer. The coated ultrasound-reflecting element is added to a hot mixture of gel, e.g., via a syringe mixer, to achieve a colloidal dispersion or suspension of the coated ultrasound-reflecting element in the gel. A tube of gel with the ultrasound-reflecting element is made, e.g., using a custom injector, and used for the long-lasting portion 100a of the marker 100 and the first fast-dissolving portion 100b of the marker 100. A tube without the ultrasound-reflecting element is made, e.g., using a custom injector, and used for the second fast-dissolving portion 100c. The tube can then be cut to desired sizes, e.g., based on each of the portions 100a, 100b, and 100c of the marker 100. A detectable object 106 (e.g., a clip or strand or coil or metal) is added, for example via a mandrel, to the tubing used for the permanent portion 100a of the marker 100. The tubing is removed from the mandrel and allowed to dry.

[0058] 1B illustrates an exemplary marker 120 for marking body tissue, the marker 120 being detectable via the systems and methods described herein. Various implementations and embodiments are not limited to use with the exemplary marker 120, but rather may be advantageously used with other markers that include an ultrasound-detectable element. The marker 120 may be, or take the form of, for example, the persistent portion 100a of the marker 100 (FIG. 1A).

[0059] The marker 120 includes a gel body 124a, multiple ultrasound-reflecting elements 102a (only two are highlighted in the detailed view) that are detectable using ultrasound (e.g., detectable using color Doppler ultrasound), and one or more detectable objects 106a that are detectable using an imaging modality other than ultrasound. The ultrasound-reflecting elements 102a can take the form of, for example, a porous or mesoporous hollow shell (as shown in FIG. 1A ) and / or a porous or mesoporous particle (as shown in FIG. 1B ), which are described in more detail herein. The detectable objects 106a can take the form of, for example, a clip, strand, or coil (e.g., metal) that is detectable using X-ray imaging, as described in more detail herein.

[0060] The ultrasound reflective elements 102 may tend to aggregate, as shown, or form agglomerates or clusters 122. A gel body 124 bonds the aggregates or clusters 122 of the ultrasound reflective elements 102 together. The aggregates or clusters 122 may be dispersed throughout the gel body 124, for example, in a colloidal dispersion. When the gel body 124 is hydrated, the aggregates or clusters 122 of the ultrasound reflective elements 102 are suspended and movable relative to each other and / or an external reference frame over at least a distance in one or more directions, which may advantageously induce or increase scattering of ultrasound backscatter.

[0061] Gel body 124 may take a variety of forms. Gel body 124 may, for example, comprise one or more hydrogels. Gel body 124 may comprise a natural hydrogel, such as gelatin. Gel body 124 may comprise an artificial hydrogel, such as polyvinyl alcohol (PVA) hydrogel or polyethylene glycol (PEG) hydrogel. Gel body 124 may comprise a combination of a natural hydrogel (e.g., gelatin) and an artificial hydrogel (e.g., PVA hydrogel, PEG hydrogel). In at least some embodiments, gel body 124 is an at least partially crosslinked hydrogel. In at least some embodiments, gel body 124 is gelatin, e.g., crosslinked gelatin. In at least some embodiments, gel body 124 is a PVA hydrogel, e.g., crosslinked PVA hydrogel. In at least some embodiments, gel body 124 is a PEG hydrogel, e.g., crosslinked PEG hydrogel. In at least some embodiments, gel body 124 comprises a combination of a natural hydrogel and an artificial hydrogel, e.g., as individual gel bodies bonded together.

[0062] The gel body 124 may not be absorbed by the body (e.g., lasting for 60 years or more), or may be absorbed by the body within a certain period of time. If absorbent, the gel body 124 may be engineered (e.g., via the degree or strength of crosslinking) to last in the body for a certain period of time, such as hours, days, weeks or weeks, months or even years. In at least some implementations, the outer or exposed portions of the absorbent gel body 124 when implanted may absorb faster than more internal portions of the gel body 124, with absorption occurring as various portions of the gel body 124 are exposed to bodily tissue, including bodily fluids. In at least some implementations, the gel body 124 may be engineered (e.g., a controlled crosslinking profile) to cause some portions to absorb faster than other portions and / or ensure some portions last longer than other portions. Thus, various absorption profiles may be formed across or through the gel body 124.

[0063] Each ultrasound reflective element is highly reflective of ultrasound. Each ultrasound reflective element preferably has an irregular surface, e.g., a rough outer surface that causes scattering or dispersion of ultrasound energy. The ultrasound reflective elements 102 may be in the nanometer size range (e.g., 1.8 microns to about 2.2 microns).

[0064] The ultrasound reflecting element 102 is typically echogenic and can take any of a wide variety of forms.

[0065] The ultrasound reflective element 102 may be porous or mesoporous, having pores and / or cavities for retaining gas. As described with reference to Figures 1A and 1B, the ultrasound reflective element 102 may include hydrophobic properties to prevent liquid ingress and "wetting" with gas (which would significantly reduce its functionality).

[0066] In at least one embodiment, each ultrasound reflecting element comprises a porous hollow shell, e.g., a silica porous hollow shell, which may or may not be spherical in shape. In at least one embodiment, each ultrasound reflecting element comprises a particle that is porous rather than a hollow shell, which may or may not be a porous non-spherical particle. Each ultrasound reflecting element may, for example, comprise a respective particle that includes or consists of silica having pores but not a single defined hollow interior cavity. Each particle may include one or more layers (not shown in FIGS. 1A and 1B ). One or more layers may include a contrast agent to enhance detection via modalities other than ultrasound imaging, as described below. Alternatively, one or more ultrasound reflecting elements may include or consist of one or more contrast agents.

[0067] The gel body 124 (e.g., a hydrogel carrier) and / or some or all of the ultrasound reflecting element 102 can optionally carry one or more contrast agents 126. The contrast agents 126 can include, for example, one or more contrast agents that enhance visual detection or detection using X-ray or MRI imaging modalities. The contrast agents 126 can include, for example, a dye to enhance detection by direct visual observation. The dye may advantageously be a fluorescent dye. The dye may include, for example, methylene blue or may consist of methylene blue. The contrast agents 126 can include, for example, a radiopaque material (e.g., gold, platinum, tantalum, bismuth, barium, etc.). The contrast agents 126 can include, for example, an MRI imaging material (e.g., gadolinium, including compounds such as gadolinium-DTPA, ferrous gluconate, ferrous sulfate, etc.).

[0068] Alternatively, one or more contrast agents 126, such as those identified above, can be incorporated within or around the gel body 124. A detectable object 106a (e.g., a clip, thread, sting coil, or helically wound metal wire, or other radiopaque element) is incorporated within or around the gel body 124.

[0069] In at least one embodiment, each ultrasound reflecting element 102 comprises a hollow shell. Each hollow shell has at least one outer wall that forms a cavity. In at least some embodiments, the hollow shell is a multi-layer hollow shell, e.g., a shell having an inner layer and an outer layer. Each hollow shell is highly reflective of ultrasound. Each hollow shell preferably has an irregular surface, e.g., a rough outer surface that causes scattering or dispersion of ultrasound energy. The hollow shells may be in the nanometer size range.

[0070] In at least some implementations, each hollow shell may comprise or consist of silica or titanium dioxide. Some techniques for forming hollow shells in the nanometer size range are described, for example, in U.S. Patent Application Nos. 60 / 955,678, 61 / 034,468, 12 / 673,224 (now U.S. Patent No. 8,440,229), International Patent Application No. PCT / US2008 / 072972, 13 / 866,940 (now U.S. Patent No. 9,220,685), 15 / 722,436, and 61 / 707. No. 794, International Patent Application PCT / US2013 / 062436, U.S. Patent Application No. 15 / 706446, U.S. Patent Application No. 62 / 135653, U.S. Patent Application No. 15 / 559764, International Patent Application PCT / US2016 / 23492, U.S. Patent Application No. 62 / 483,274, U.S. Patent Application No. 62 / 645,677, U.S. Patent Application No. 15 / 946,479, and International Patent Application PCT / US2018 / 26291.

[0071] In some implementations, the hollow shell or porous particle, or one or more layers of the hollow shell or porous particle, may include one or more contrast agents, such as those identified above to enhance visual, radiological, or MRI detection.

[0072] In at least some implementations, the cavities and / or pores of the ultrasound reflecting element 102 contain a fluid that is a gas, a liquid, or a combination or mixture of gas and liquid, typically a gas that remains in a gaseous state even during interrogation with ultrasonic energy during use. The gas may take the form of one material, and the liquid may take the form of another material different from the material that forms the gas. Alternatively, the gas and liquid may be the same material, simply in different phases. The combination or mixture of gas and liquid may take the form of a vapor, for example, at rest or when exposed to ultrasound at a threshold level of energy that causes heating. The cavities of the at least one hollow shell may contain, for example, air. Alternatively, the cavities and / or pores of the ultrasound reflecting element 102 may contain an inert gas (e.g., nitrogen, argon). The cavities and / or pores preferably do not contain perfluorocarbons, for example, whether in gas and / or liquid form.

[0073] Each ultrasound reflecting element 102 may be porous or mesoporous. When the ultrasound reflecting element 102 contains a fluid (i.e., a gas, a liquid, or a combination or mixture of a gas and a liquid), the ultrasound reflecting element 102 may optionally and preferably include a coating for sealing the cavities and / or pores, preferably a hydrophobic coating, which at least temporarily seals the cavities and / or pores thereof and prevents ingress of fluid from body tissue into the pores or cavities of the ultrasound reflecting element 102.

[0074] In some implementations, the gel body 124 may be expandable, for example, when implanted in bodily tissue. In some implementations, the marker 120 may have a length of about 2 mm to about 40 mm and a transverse dimension of about 0.5 mm to about 2 mm in an unexpanded state. The marker may have a size expansion ratio from a dry, unexpanded state to a water-saturated, expanded state of about 1:1.5 to about 1:10. The marker 100 may have a size expansion ratio from a dry, unexpanded state to a water-saturated, expanded state of about 1:2 to about 1:3.

[0075] The present disclosure also generally relates to markers 100, 120 (e.g., tissue markers) having physical characteristics that make the markers 100, 120 more readily identifiable via Doppler ultrasound (e.g., color Doppler ultrasound) when the markers 100, 120 are implanted in bodily tissue. Such markers 100, 120 may include a gel body 104, 124 having a plurality of ultrasound-reflective elements 102a, 102b, 102c (e.g., porous shells, porous particles) suspended within the gel body 104, 124. The ultrasound-reflective elements 102a, 102b, 102c may be dispersed throughout the gel body 104, 124, for example, in a colloidal dispersion or colloidal suspension.

[0076] The gel bodies 104, 124 may take the form of a hydrogel. The gel bodies 104, 124 may be fully or partially crosslinked so long as, when the gel bodies 104, 124 are hydrated, the ultrasound reflective elements 102a, 102b, 102c are free to move (e.g., swing or vibrate) in at least one dimension (e.g., along at least one axis, preferably along two or more axes) to a degree or distance sufficient to enhance any scattered return from the ultrasound reflective elements 102a, 102b, 102c in response to ultrasound interrogation of the markers 100, 120.

[0077] The ultrasound reflective elements 102a, 102b, 102c typically have irregular surfaces that result in scattering (e.g., backscatter) in response to ultrasonic interrogation of the markers 100, 120. The ultrasound reflective elements 102a, 102b, 102c typically retain fluid (i.e., gas, liquid, or a combination of gas and liquid), which enhances backscatter in response to ultrasonic interrogation of the markers 100, 120. The ultrasound reflective elements 102a, 102b, 102c typically include a hydrophobic coating (e.g., silicone) that retains fluid (e.g., air) within the shell for extended periods of time, even when the markers 100, 120 are exposed to bodily fluids for extended periods of time (e.g., 3 months, 9 months, 18 months). Such advantageously prevents the ultrasound reflective elements 102a, 102b, 102c from "wetting" (which would reduce or even eliminate detectable scattering). The gel bodies 104, 124 can be dried or dehydrated or freeze-dried until implanted into body tissue, and then hydrate over a period of time as fluid (e.g., water) is absorbed from the body tissue. The gel bodies 104, 124 also provide a framework for bioadhesion through the natural healing process of the fibers of the body tissue into which the markers 100, 120 are embedded. As such, they can secure the markers 100, 120 in place within the body tissue without the use of glues or adhesives.

[0078] These various described physical structures or physical properties of the markers 100, 120 provide or enhance scattering (e.g., backscatter) of ultrasound from the markers 100, 120, and in particular contribute to changes in the position and / or velocity of the ultrasound reflective elements 102a, 102b, 102c, either individually or in aggregates or clusters 122, with the resulting broad velocity spectrum contributing to detectability using Doppler ultrasound techniques. The physical properties of the ultrasound reflective elements 102a, 102b, 102c or aggregates or clusters 122 of the ultrasound reflective elements 102a, 102b, 102c of different ones of the marker 100 may vary from persistent portion 100a to persistent portion 100a and / or from fast-dissolving portion 100b to fast-dissolving portion 100b, allowing two or more different persistent portions 100a to be easily distinguished from one another based on distinguishable response signals, and / or allowing two or more fast-dissolving portions 100b to be easily distinguished from one another based on distinguishable response signals.

[0079] The response of the markers 100, 120 depends on the vibration of the ultrasound-reflecting elements 102a, 102b, and 102c in the hydrogel matrix. The vibration is affected by several factors. For example, the vibration is affected by the limiting crosslink length of the PEG (50-100 nm between the four arm junctions), which limits the range of motion of the ultrasound-reflecting elements 102a, 102b, and 102c in the at least partially crosslinked gel matrix. Furthermore, for example, the movement of the ultrasound-reflecting elements 102a, 102b, and 102c from the incident transmit wave is limited by the size range of the ultrasound-reflecting elements 102a, 102b, and 102c (e.g., ~2 μm) and the size range of the aggregates or clusters 122 of ultrasound-reflecting elements 102a, 102b, and 102c (~2 to ~6 porous shells per cluster, for an aggregate or cluster size of approximately 12 μm). Also, for example, vibrations are affected by the span of interstitial hydrogel between the hydrophobic aggregates or clusters 122 of ultrasound-reflecting elements 102a, 102b, 102c (i.e., where ultrasound-reflecting elements 102a, 102b, 102c are absent), which spans range from about 3 um to about 15 um inclusive, typically having a distance of about 6 um to about 9 um inclusive. By way of further example, vibrations are affected by the polymer blend crosslink density, which can be characterized, for example, by a measure of water swelling at 15 times the dry mass of the polymer matrix.

[0080] Furthermore, the excitation frequency affects the motion behavior of the ultrasound reflective elements 102a, 102b, 102c, which has a maximum at a particular frequency (e.g., MHz). For example, a PEG PEG amine hydrogel design with ultrasound reflective elements 102a, 102b, 102c at a concentration of 8 mg / ml per pad of gel has peak dispersions at 2.76 MHz, 3.33 MHz, and 4.44 MHz.

[0081] In one example, the agglomerates or clusters 122 of ultrasonic reflecting elements 102a, 102b, and 102c have dimensions of approximately 10 μm to approximately 30 μm and are coated or sealed to prevent liquid ingress. Backscattering perturbed by the ultrasonic reflecting elements 102a, 102b, and 102c generates extra harmonics in the return signal, which can be enhanced by frequency selection. Varying the wavelength of the ultrasonic interrogation or transmission signal to match the scattering structure (e.g., across 500 ultrasonic reflecting elements 102a, 102b, and 102c) advantageously results in a broad velocity spectrum. Bridging, like agglomeration, affects the range of motion of the ultrasonic reflecting elements 102a, 102b, and 102c. Bridging is typically characterized on the order of angstroms, while the size of the ultrasonic reflecting elements 102a, 102b, and 102c is typically characterized on the order of microns.

[0082] FIG. 2 shows a marker 200 implanted in body tissue 202 and an ultrasound system 204 having an ultrasound probe or transducer array 206 positioned to detect the marker 200, according to at least one illustrated embodiment.

[0083] The ultrasonic system 204 includes a transmit section 208 and a receive section 210. The transmit section 208 generates drive signals to drive the ultrasonic probe or transducer array 206 to emit ultrasonic energy pulses (e.g., an ensemble of pulses along each beam or angle from each ultrasonic piezoelectric element, crystal, or transducer of the ultrasonic probe or transducer array 206). The receive section 210 receives signals representative of ultrasonic energy detected by the ultrasonic probe or transducer array 206 (e.g., a return signal or series of return signals that may constitute scattered or backscattered returns of ultrasonic energy from a marker or portion of a marker) and processes the received signals to identify and / or locate the marker based on a known transmit model (e.g., pulse ensemble, pulse repetition frequency) using a receive signal processing chain (examples of which are described herein). The ultrasonic system 204 may operate in any one or more modes of operation (e.g., A-mode, B-mode, M-mode, color Doppler mode, power Doppler mode). In some implementations, the ultrasound system 204 alternates between modes (e.g., alternates between capturing B-mode frames to image anatomical structures and capturing color Doppler mode frames to detect responses from markers with echogenic characteristics).

[0084] The transmit section 208 has an associated base or fundamental frequency, i.e., the base or fundamental frequency of the ultrasonic signal emitted by the ultrasonic probe or transducer array 206. Such may be, for example, in the range of 2 MHz to 20 MHz, inclusive.

[0085] The ultrasound system 204 includes a master clock or oscillator 212 that outputs a timing signal. The timing signal output by the master clock or oscillator 212 may be set or used to set, for example, a nominal pulse repetition frequency (PRF), which is the frequency at which ultrasound pulses are repeated. In at least some implementations, the nominal pulse repetition frequency may advantageously be a default value or may be automatically set, for example, based on the type of marker being used and / or the type of ultrasound probe or transducer array 206 being used. Less preferably, the nominal pulse repetition frequency value may be set by an operator, at least within a defined range. In other implementations, the nominal pulse repetition frequency may be a fixed characteristic of a particular ultrasound system 204 and / or marker 200 and / or ultrasound probe or transducer array 206.

[0086] As described herein, in some implementations, the transmit section 208 of the ultrasound system 204 optionally introduces variations (e.g., nonlinearities) in the ultrasound energy emitted by the ultrasound probe or transducer array 206, and the receive section 210 may use the variations (e.g., nonlinearities) in the received ultrasound energy (e.g., a return signal or series of return signals that may constitute scattered or backscattered returns of ultrasound energy from a marker or portion of a marker) to facilitate marker detection (e.g., matched filtering). For example, in at least some implementations, the transmit section 208 preferably includes a variation circuit (VAR) 214 that introduces one or more variations, preferably nonlinear variations, into the ultrasound transmission. The nonlinear variations in the ultrasound transmission can take any one or more of a variety of forms and enhance the ability of the systems and methods described herein to reliably detect markers in body tissue. It should be noted that various implementations of the receive section 210 and associated receive signal processing chain may successfully operate without introducing variations or nonlinear variations into the outgoing ultrasound transmission. It should also be noted that various implementations of the receive section 210 and associated receive signal processing chain may, in at least some instances, be simplified with respect to the illustrated implementation, where variations, such as nonlinear changes, are introduced into the transmit model, allowing, for example, for omission or simplification of some of the filtering, signal processing, or image processing, and / or culling included in the illustrated receive signal processing chain.

[0087] Nonlinear variations in ultrasonic transmissions may include, for example, variations in magnitude or voltage, and therefore variations in the output power of the ultrasonic transmissions. Additionally or alternatively, nonlinear variations may include, for example, variations in pulse repetition frequency (PRF), which indicates the number of ultrasonic pulses emitted by the ultrasonic probe or transducer array 206 over a specified period of time (e.g., typically between 1 kHz and 10 kHz). Alternatively or additionally, nonlinear variations may include, for example, variations in the base frequency of the ultrasonic transmissions emitted by the ultrasonic probe or transducer array 206. Thus, any variations may be variations in any one or more of magnitude or voltage, time, frequency, and / or phase. Any variations may be implemented, for example, via one or more resistors or rheostats to adjust the magnitude, or via one or more delay circuits or capacitors to delay, for example, a clock signal. The variations may be periodic, follow a pattern, or may be pseudorandom numbers, for example, generated via a pseudorandom number generator, also known as a random number generator (RNG). By way of example, optional variations may be provided to the amplifier 218 to change the amplitude or voltage, as indicated by the dashed arrows, or to the gate generator 216 to change the PRF or phase or otherwise change the base or fundamental frequency of the ultrasonic transmission. Variations may also be provided to the receive section 210 for use in identifying which received ultrasonic signals correspond to responses returned by the marker.

[0088] The receive section 210 receives signals (e.g., raw RF) representing ultrasonic energy detected by the ultrasonic probe or transducer array 206 (e.g., a return signal or series of return signals that may constitute scattered or backscattered return of ultrasonic energy from a marker or portion of a marker). The signals typically represent ultrasonic energy reflected or otherwise returned from objects within the field of view of the ultrasonic probe or transducer array 206. These objects may include the markers themselves as well as body tissue. The signals representing ultrasonic energy detected by the ultrasonic probe or transducer array 206 may also represent outgoing ultrasonic transmissions (i.e., outgoing ultrasonic pulses from the ultrasonic probe or transducer array 206 toward body tissue) as well as other noise. The receive section 210 includes an advanced receive signal processing chain 220 that includes various receive signal processing stages to remove noise, increase the signal-to-noise ratio, and identify, recognize, and / or locate or localize signals representing ultrasonic energy returned from the markers. For ease of discussion, signals representing ultrasonic energy detected by the ultrasonic probe or transducer array 206 are sometimes referred to herein as received signals. While transmitted ultrasound is typically broadband, the present systems and methods may advantageously use ultrasound detected or received in narrow bands, e.g., ultrasound detected or received in two narrow bands where harmonics of the response from the marker are prominent against the background (e.g., about 1.5 times the base of the fundamental frequency and about 2 times the base of the fundamental frequency of the transmitted ultrasound). As described herein, a frame-by-frame analysis may be performed to identify relatively large movements of echogenic material through artifacts representing harmonics.

[0089] The receive section 210 may include one or more amplifiers 222 for amplifying received signals (e.g., a return signal or series of return signals that may constitute scattered or backscattered returns of ultrasonic energy from a marker or portion of a marker) detected by the ultrasonic probe or transducer array 206. Any or a variety of amplifiers suitable for amplifying signals from the ultrasonic probe or transducer array 206 may be used.

[0090] The receive signal processing chain 220 may optionally include a DC canceller 224 that cancels DC components from the receive signals detected by the ultrasound probe or transducer array 206 .

[0091] The receive signal processing chain 220 may optionally include one or more matched filters 226 (e.g., pulse matched filters) that filter the amplified signal, for example, to pass detected reflected or returned ultrasonic pulses that match the pattern of the transmitted ultrasonic pulses and to reject noise and other signals.

[0092] The receive signal processing chain 220 includes a set of RF stages 228. The RF stages 228 process the beam-formed RF data, for example, applying RF filters and mixing. The RF stages 228 are described in more detail with respect to FIG. 4 below (see RF stage 416).

[0093] The receive signal processing chain 220 includes a set of detector stages 230. The detector stages 230 demodulate the raw RF data. The detector stages 230 are described in more detail with respect to FIG. 4 below (see detector stage 418).

[0094] The receive signal processing chain 220 may include a set of target stages 232. The target stages 232 perform spatial or "image" processing on data representing the ultrasound signals detected by the ultrasound probe or transducer array 206 (FIG. 2). The target stages 232 are described in more detail with respect to FIG. 4 below (see target detection stage 424).

[0095] The receiving section 210 may include one or more presentation stages 234. The presentation stage 234 processes data, e.g., data representing marker positions or centroids, and optionally data representing anatomical structures, allowing it to be presented to a user, for example, via a display screen or other visual and, optionally, audible cues. For example, a representation of the marker positions or marker centroids may be visually represented on a display screen overlaid or superimposed on a low-resolution representation of the anatomical structures (e.g., captured during B-mode operation) to facilitate visualization of the marker positions relative to various anatomical features of the body. In at least some examples, the marker centroids may correspond to the location of sparkle or twinkle effects in color ultrasound imaging. The presentation stage 234 is described in more detail with respect to FIG. 4 below (see scan converter 430 and associated beam geometry 431 and associated B-map data 432, image filter stage 434, scan converter 436, image filter stage 440, image merger 442, and image pane 444).

[0096] 3 illustrates an exemplary configuration of an ultrasound system 300, according to at least one exemplary embodiment. Ultrasound system 300 may be, for example, an implementation of ultrasound system 204 (FIG. 2).

[0097] The ultrasound system 300 may include a housing or console that houses an electronics assembly, for example, using three custom subassembly circuit cards, a single-board computer, and a custom power subassembly. The ultrasound system 300 preferably includes all executable instructions (e.g., software, firmware) that run internally on appropriate hardware (e.g., a processor) and user outputs provided to an LCD screen and speaker that are part of the ultrasound system 300 and preferably housed by the housing or console. In normal use, only two other electrical connections are made to the ultrasound system 300: one to the ultrasound probe or transducer array 206 and the other to AC line power (e.g., a power outlet).

[0098] The ultrasonic probe or transducer array 206 is preferably a self-contained transducer assembly (e.g., including a linear or two-dimensional array of piezoelectric elements, crystals, or transducers). The ultrasonic probe or transducer array 206 connects to the back of the housing of the ultrasonic system 300. The ultrasonic probe or transducer array 206 can be removed and replaced, for example, if defective. The ultrasonic probe or transducer array 206 is managed by and specifically matched to the ultrasonic system 300. In at least some implementations, the ultrasonic probe or transducer array 206 can take the form of, for example, a passive ultrasound probe. In at least some implementations, the ultrasonic probe or transducer array 206 can provide, for example, an identification capability. User interaction with the ultrasound system 300 is preferably minimized to, for example, turning on the ultrasound system 300, placing the ultrasound probe or transducer array 206 over a body part and / or moving it relative to a body part until a response is provided, and requiring the user to set any values ​​or operating parameters.

[0099] The ultrasound system 300 may include, for example, a computer, preferably a single board computer (SBC) 302, and may also include an ultrasound main board 304 communicatively coupled to the SBC 302 via a hardware interface 306 and any associated drivers (e.g., software or firmware communication drivers).

[0100] The ultrasound system 300 may further include, for example, one or more cards or boards (e.g., referred to herein as carrier cards) (not shown in FIG. 3 ) for managing and distributing power and / or communications, for example. The carrier card may, for example, connect and power all components in the ultrasound system 300, such as the system power supply, SBC 302, ultrasound main board 304, display monitor, USB connector, audio speaker, fan, thermistor, and power on switch. The carrier card may also have circuit components such as, for example, a tracking transmit regulator, a magnetic high voltage supply (magnetic), an audio amplifier, and / or a fan motor controller.

[0101] The SBC 302 may include one or more processors and one or more memories or other non-transitory storage media communicatively coupled to the one or more processors. The processor may include, for example, one or more of a microprocessor, a microcontroller, a central processing unit (CPU), a digital signal processor (DSP), a graphics processing unit (GPU), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), and / or a programmed logic controller (or programmable logic controller / PLC). The memory may include, for example, one or more of a read-only memory (ROM), a random-access memory (RAM), an EEPROM, a flash memory, and / or a register. Other non-transitory storage media may include, for example, one or more of a magnetic disk and associated magnetic disk drive, an optical disk and associated optical disk drive, and / or a solid-state drive (SSD), etc. In the illustrated implementation, single-board computer 302 is shown as including a CPU 308 (e.g., a microprocessor CPU) and a GPU 310 communicatively coupled to CPU 308, although one skilled in the art will understand that other sets of components and configurations of those components are possible and the illustrated implementation is not intended to be limiting.

[0102] The SBC 302 controls the overall operation of the ultrasound system 300 and communicates through many different types of interfaces, such as a front panel interface, a front audio interface, USB 2.0 and 3.0 interfaces, a PCIe interface, and a power input interface. The carrier card routes these signals to the appropriate destination connector. The use of a separate card or board (e.g., a carrier card) facilitates modifications to the ultrasound system 300, for example, allowing future modifications to the SBC 302 to use different hardware and / or operating systems.

[0103] The SBC 302 may be powered from the system +12V supply distributed through the carrier card. The SBC 302 also shares a common ground with the ultrasound system 300. The connector may take the form of, for example, a two-pin Samtec IPL-style connector that supports both a specified maximum inrush current and steady-state current from the SBC 302.

[0104] The front panel connector connects the system power-on switch to the SBC 302 via the PSWIN connection and GND. The PWSIN signal is an active-low signal that signals power on or power off to the SBC 302. This signal is preferably momentarily shorted to ground to initiate the power-on or power-off sequence; therefore, the power switch may be implemented as a momentary-on, single-pole switch. There may also be two LED signals indicating system power status (SUS) and hard drive activity (HD). These two signals may be active-low signals and may be connected to the P3v3 SBC supply pins for operation. Two LEDs and two resistors are used, one for each signal, to provide a suitable visual indication of the status of these two signals. There may also be a GND pin for power and signal return currents that should be connected to the common system ground and +3.3V supply used to power the LEDs, as mentioned above. The front audio connector is used to interface with the carrier card's audio amplifier. The audio connection may be pseudo-differential and therefore may be routed to the input of the audio amplifier with the appropriate audio ground.

[0105] The power distribution network can consist of switches and linear regulators, and the switches can be synchronized with the system image clock. For example, a P5v2 SMPS and a P5V0 regulator can be used to power the circuits on the carrier card. The SMPS output voltage can be set by the dropout voltage of the P5v0 linear regulator. The SMPS monitors the amplitude of the P12v0 signal and uses two threshold voltages to determine when to change the state of the Power good signal (PG_P5v2). This signal is used to enable or disable the HV clamp circuit and disable or enable the HVP and HVM power supplies. Also, for example, an M5v6 SMPS and an M5V0 regulator can be used to power the circuits on the carrier card. The SMPS output voltage can be set by the dropout voltage of the M5v0 linear regulator.

[0106] The transmit clamp and enable circuit can be used to place the transmit power supply in a safe state during system power-off or power-on sequences. This circuit uses the proper timing sequence between the two signals to ensure sufficient dead time. The FPGA preferably performs the break before creating the switching topology. To perform the proper power-on and power-off sequence of the HVP and HVM power supplies, an active clamp circuit with an active power enable circuit can be used. These two signals can be controlled by hardware to perform the timing sequence used to perform the break before creating the switching topology. The HV clamp and HV enable circuits have two operating states: active clamp and power supply disabled, and disabled clamp and power supply active. These two states are triggered by the P5v2 SMPS power good signal. This signal is the output of the P5v2 SMPS regulator, which actively monitors the voltage of the P12v0 power supply using the SMPS UVLO circuit. An active high or +12V on the PG signal indicates that the P12v0 voltage is UVLO, which means that the P12v0 power supply is fully on and the HVP and HVM power supplies can also be safely turned on. rising An active low or 0V on the PG signal indicates that the P12v0 power supply is in UVLO mode, which means that the system has a fault or is powered off. falling In either case, the HVP and HVM supplies are disabled and clamped to ground.

[0107] The SBC USB 2.0 connector can take the form of a ribbon cable type connector used to interface between the SBC302 and the carrier card. There are two sets of HS USB 2.0 signaling used to communicate between the SBC302 and either the touch panel or the maintenance port. These are standard USB 2.0 interfaces including VBus, Gnd, and a pair of differential signals.

[0108] The USB 3.0 connector may take the form of a standard USB 3.0 compliant connector. The connection between the SBC 302 and the carrier card is made by connecting a standard USB 3.0 interface cable between the two connectors. This is the primary communication path from the SBC 302 for transferring data to and from the ultrasound main board 304.

[0109] The single-board computer 302 implements an operating system 312 that controls the overall operation of the ultrasound system 300, including system startup and system checks, and optionally controls certain operations related to the detection of markers and / or the presentation of outputs (e.g., visual and / or audible) indicative of the location of detected markers.

[0110] The single-board computer 302 executes a detector application 313 that controls certain detector-related operations of the ultrasound system 300, such as the processing of ultrasonic energy detected by the ultrasound probe or transducer array 206 (FIG. 2) via a receive signal processing chain, as described below.

[0111] In at least some implementations, the CPU 308 executes a workflow state machine to perform configuration management 314. For example, the workflow or operations from starting up the ultrasound system 300 to processing received signals and presenting data may be specified as various states of a state machine executed by the CPU 308. Also, for example, the CPU 308 may configure the ultrasound system 300 based on, for example, a default set of parameters.

[0112] The CPU 308 may also execute logic for processing the user feedback management and control 316. For example, the CPU 308 may generate a visual representation of the position of the detected marker relative to a visual representation of the anatomical structure and / or a visual representation of the position of the ultrasound probe or transducer. Also, for example, the CPU 308 may generate an audible representation of the position of the detected marker relative to the position of the ultrasound probe or transducer in one, two, or three dimensions, and / or an audible representation of the direction of movement of the ultrasound probe or transducer relative to the detected marker (e.g., a beep or other sound corresponding to movement away from and / or towards the marker).

[0113] The CPU 308 may also execute logic for processing system setting management and control 318. For example, the CPU 308 may manage a set of settings for the ultrasound system 300, for example, using a default set of system settings or using system settings based on i) the type of ultrasound probe or transducer communicatively coupled to the ultrasound system 300, ii) the type of marker used, and / or iii) the type of body tissue in which the marker is implanted (e.g., breast, lung).

[0114] The GPU 310 can implement an ultrasound processing pipeline 320, which is described in more detail herein (e.g., see FIG. 4, receive signal processing chain 402), to process returned ultrasound (or retuned ultrasound) received by the ultrasound probe or transducer array 206 (FIG. 2). The GPU 310 can implement a detection metric 322 to execute logic to detect markers from the detected ultrasound, which is described in more detail herein (e.g., see FIG. 4, receive signal processing chain 402). The GPU 310 may execute logic to perform image compositing (or image composting) 324 to generate image data that can be presented (e.g., displayed) to a user, as described in more detail herein (see, e.g., Figure 4: scan converter 430 and associated beam geometry 431 and associated B-map data 432, image filter stage 434, scan converter 436, image filter stage 440, image merger 442, and image pane 444).

[0115] The ultrasound main board 304 can perform local and ultrasound probe control and is used for various image sequence events. The ultrasound main board 304 may, for example, embody firmware 323. While the ultrasound main board 304 is shown using a processor 325 in the form of an FPGA, the ultrasound main board 304 may more preferably use one or more GPUs to improve operational speed.

[0116] The ultrasound main board 304 may include a software and firmware stack (e.g., Cypress USB) 326 for implementing communications between the ultrasound main board 304 and external devices, which may enable communication with an attached ultrasound probe or transducer array 206 ( FIG. 2 ) and enable programming of the ultrasound main board 304's processor 328 (e.g., FPGA or GPU). For example, the ultrasound main board 304 may include one or more communication ports (e.g., two communication ports, not shown in FIG. 3 ) that provide a communication interface with external devices. One port may take the form of a probe port, for example, that interfaces with an ultrasound probe and is used to carry ultrasound transmit (TX) and ultrasound receive (RX) electrical signals to and from the ultrasound probe or transducer array 206, respectively. The probe port may have appropriate contacts or pins and / or may include physical mating features or structures for communicatively interfacing (e.g., electrically) with complementary structure on the ultrasound probe or transducer array 206 ( FIG. 2 ). As described elsewhere herein, an optional communication port, referred to as a magnetic resonance port, may be included to provide synchronous magnetic pulses.

[0117] The ultrasound main board 304 can include a processor 325 (e.g., FPGA or GPU) that is the center of imaging and diagnostic control via an ultrasound probe port and optionally via a magnetic port. Although the processor 325 is shown as an FPGA, one or more GPUs can be advantageously used in some implementations.

[0118] The processor 325 of the ultrasound main board 304 may, for example, implement a scan state machine 330 to control scanning by the ultrasound probe or transducer array 206 (FIG. 2). The processor 325 of the ultrasound main board 304 may, for example, execute logic that provides front-end chip register access 332. The processor 325 of the ultrasound main board 304 may, for example, perform beamforming 334 on the received or returned ultrasound signals, activating the transducer array elements in a controlled manner during reception of ultrasound energy to form a high-quality set of ultrasound image data of the region of interest. Any of a variety of beamforming techniques may be used.

[0119] 4 illustrates an example receive signal chain 400 for an ultrasound system, in accordance with at least one example embodiment. The ultrasound system may be, for example, an implementation of ultrasound system 204 (FIG. 2) or 300 (FIG. 3).

[0120] Typically, an ultrasound probe or transducer having multiple individual piezoelectric elements, crystals, or transducers transmits outward ultrasound pulses, e.g., grouped as an ensemble of pulses along each of multiple beam directions (e.g., an ensemble of pulses from each piezoelectric element, crystal, or transducer along the primary axis of emission of the respective piezoelectric element, crystal, or transducer). The ultrasound probe detects the ultrasound energy, and the receive section of the ultrasound system performs processing to identify or locate (or localize) the detected ultrasound energy corresponding to the response by the marker from all other detected ultrasound energy. The processing should balance computational accuracy and speed. In particular, the processing must be fast enough to accommodate the movement of an ultrasound probe, which is useful in a surgical environment and is typically handheld, and therefore may move at varying speeds (e.g., speed and direction) and even be swung. For example, to increase accuracy, it may be desirable to locate the response from the marker multiple times. However, doing so may increase the time it takes to transmit a pulse, receive a response, and process the received response. In at least some implementations, a marker's response signature is considered detected if it is found in three (3) consecutive frames of captured ultrasound data.

[0121] Ultrasonic energy detected by the ultrasonic probe or transducer array 206 (FIG. 2) may be represented by a signal (received signal) that may be processed via a receive signal processing chain 402 of the receive signal chain 400. The receive signal processing chain 402 may be implemented via circuitry and / or processor-executable instructions stored in a non-transitory form on one or more tangible media (e.g., non-volatile memory, spinning storage media such as magnetic hard disk drives, optical disk drives, or solid-state storage media such as solid-state drives (SSDs) or FLASH memory), the processor-executable instructions being executable by one or more processors (e.g., microcontrollers, microprocessors, central processing units (CPUs), application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), digital signal processors (DSPs), and / or graphics processing units (GPUs)). The receive signal processing chain 402 may be performed, for example, via an FPGA, or more preferably by one or more GPUs.

[0122] In particular, the ultrasound probe or transducer array 206 (FIG. 2) may pass signals through a cable 404 and a communication driver 406 (e.g., a USB driver, a PCIe driver) and a hardware interface 408 (e.g., a USB-compliant port or connector, a PCIe-compliant port or connector).

[0123] The signals may be accumulated via a frame stream buffer 410 implemented by a frame data manager. The frame data manager stores, maps, or otherwise arranges (i.e., beammaps) the RF beam data in an arrangement or format expected by the receive signal processing chain 402, for example, by storing the signals in the frame stream buffer 410 in a specified format. The format or arrangement may be specified, for example, in a storage medium (e.g., a non-volatile or read-only memory or EEPROM labeled beam SIM 412). Note that the receive signal chain may include a cable 404, a communication driver 406, a hardware interface 408, a frame stream buffer 410, and / or a beam SIM 412 in addition to the components of the receive signal processing chain 402.

[0124] Thus, the receive signal processing chain 402 may start with, for example, a full frame of beamformed RF data dispatched from the frame stream buffer 410 by the frame data manager.

[0125] The receive signal processing chain 402 may optionally implement a DC canceller 414 to cancel DC components in the beamformed RF data received from the frame stream buffer 410. The DC canceller 414 (also called an ensemble canceller) may, for example, apply means cancellation and depth-based gain to remove the average to account for differences (see, e.g., ensemble canceller 506 in FIGS. 5A, 5B, and 5C).

[0126] The receive signal processing chain 402 may include one or more RF stages 416 to process the beamformed RF data, e.g., to improve the signal-to-noise ratio. The RF stage 416 may, for example, perform RF filtering and / or mixing. The RF stage 416 may, for example, split the raw RF data. For example, the RF stage 416 may separate or split raw RF data (pulse ensemble data) representing responses from markers from raw RF data (e.g., non-pulse ensemble data or B data) representing other types of returns or reflections that may represent reflections from anatomical structures (e.g., 508, FIGS. 5A-5C). For example, the RF stage 416 may use one or more RF filters (e.g., finite impulse response (FIR) bandpass filters) to perform such real-time digital signal processing. The RF stage 416 may, for example, process multiple streams of RF data, e.g., two streams of pulse ensemble RF data and a stream of B RF data. For example, the RF stage 416 may include several mixers (e.g., 510a, 510b, 510c, FIGS. 5A-5C) that generate RF in-phase or direct quadrature (IQ) signals for various streams of pulse ensemble RF data and non-pulse ensemble RF data. For example, the mixers (e.g., 510a, 510b, FIGS. 5A-5C) may mix two streams of pulse ensemble data with respective multiples of the base or fundamental frequency of the transmitted ultrasound waves (e.g., 1.5 times the base or fundamental frequency and 2 times the base or fundamental frequency). The RF mixing can result in two or more different multiples of the base or fundamental frequency of the ultrasound waves. Note that using 1.5 times the fundamental frequency has been found to produce better results than using only 2 times the fundamental frequency because it addresses a possible "blinding effect" by removing ultrasound signals detected by the ultrasound probe that are actually transmitted ultrasound signals rather than returned signals. RF stage 416 may also use one or more low pass filters (eg, 512a, 512b, 512c, see FIGS. 5A-5C), for example, to remove negative frequencies from the IQ signals.The RF stage 416 may also use one or more notch filters, for example, to filter out the fundamental frequency of the ultrasound.

[0127] The receive signal processing chain 402 may include one or more detector stages 418. The detector stages 418 may demodulate the separated raw RF data. Demodulation, commonly referred to as detection, removes the carrier signal and reconstructs a signal envelope (e.g., envelope detection) for each stream of RF data (e.g., 514a, 514b, 514c, FIGS. 5A-5C). Thus, the detector stages 418 may, for example, remove the transducer pulse frequency from the data and prevent or reduce ripple. Envelope detection may, for example, demodulate or convert the RF signal back to an amplitude representation.

[0128] Various approaches can be used to perform demodulation or envelope detection, such as i) implementing quadrature (IQ) detection or ii) applying a Hilbert transform. Quadrature (IQ) detection mixes (essentially multiplies) in-phase and quadrature-phase sinusoids with the input signal to emphasize the signal content at that frequency and reduce all other content. Such approaches can be implemented in hardware or software. The raw signal after IQ detection may still contain ripple (e.g., at twice the carrier frequency), which can be advantageously addressed via low-pass filtering. Applying the Hilbert transform shifts the peak of the ripple in the RF data midway in time toward the trough. The resulting modified signal can be combined with the original signal so that one fills in the ripple of the other, thereby estimating the magnitude of the envelope. The result is a good approximation of the pulse energy, reducing the ripple while maximizing detail.

[0129] The receive signal processing chain 402 may optionally perform a logarithmic compression (ie, log compress) 420 on the output from the RF stage 416 .

[0130] The receive signal processing chain 402 may optionally perform logarithmic compression (ie, log compression) 422 on the output from the detector stage 418 .

[0131] The receive signal processing chain 402 may include one or more target stages 424 for performing spatial or "image" processing on data representing ultrasound signals detected by the ultrasound probe or transducer array 206 (FIG. 2). The target stage 424 may, for example, perform frame-to-frame comparison, referred to herein as sigma mapping, to identify, for example, changes or differences between frames of received ultrasound data (e.g., 518, FIGS. 5A-5C). Sigma mapping may, for example, maximize signal-to-noise by extracting target responses (e.g., return signals from markers) within the received signal data. The target stage 424 may also include target detection (e.g., 520, FIGS. 5A-5C), for example, using a target best-fit algorithm. The target best-fit algorithm isolates the blob that best matches the target spatial criteria (e.g., the shape of the marker's ultrasound response).

[0132] The receive signal processing chain 402 may include one or more focus mixers 426 (also called focal mergers). The focus mixer 426 takes data from multiple focus depths from the previous stage and flattens the data. For example, the focus mixer 426 may take data from two focus depths (e.g., 48 x 2640 x 2 data) and generate a smaller data set (e.g., 48 x 2640 data). The focus mixer 426 may combine B focused beams and allow a detector to intersect the B streams (e.g., 530, Figures 5A-5C).

[0133] The receive signal processing chain 402 may perform one or more decimations 428 to reduce the size of the data set. For example, the receive signal processing chain 402 may perform detector decimation on the samples within the beam (e.g., detector decimation 522, FIGS. 5A-5C) and B sample decimation (e.g., B sample decimation 528, FIGS. 5A-5C).

[0134] The receive signal processing chain 402 may include one or more scan converters 430, 436, associated beam geometry 431, associated B map data 432, and associated color map data 438. The scan converters 430, 436 output scan conversion for B-mode image data and color mode image data (e.g., D scan conversion 524, FIGS. 5A-5C; B scan conversion 532, see FIGS. 5A-5C).

[0135] The receive signal processing chain 402 may include one or more image filter stages 434, 440 for filtering various components of the image or image data (eg, B-mode image data, color mode image data).

[0136] The receive signal processing chain 402 may include one or more image mergers 442 operable to merge image data (eg, B-mode image data with color-mode image data).

[0137] The receive signal processing chain 402 may include one or more image panes 444 operable to present the merged image data.

[0138] The receive signal chain 400 for an ultrasound system may include a system interface (Vdevice model) 446 for reading registers and tables, for example.

[0139] The receive signal chain 400 for an ultrasound system may include, for example, a graphics interface (Pipleline DeviceVM View Model) 448, which is an interface between, for example, a graphics engine (C++ CLR interface) 450 and a presentation framework (e.g., WPF for Windows applications) 452 to present images via a display screen and / or driver (View) 454 via a markup language layer (XAML UI DEF) 456. The Pipeline Device VM View Model 448 reads and writes external files (e.g., configuration or current files 458) and external libraries (e.g., scripts 460).

[0140] 5A-5C show a method 500 for processing received ultrasound energy to identify responses from markers and provide visual and / or audible indications of the presence and / or location of the markers, in accordance with at least one illustrated embodiment, detailing, in particular, an implementation of RF demodulation. Method 500 may be performed, for example, by receive section 210 (FIG. 2) of ultrasound system 204.

[0141] Method 500 may be implemented in hardware, software, and / or firmware according to at least one illustrated embodiment. Hardware may include, for example, an analog-to-digital converter (ADC), a processor-based computer system employing one or more processors and memory or other non-transitory storage media, as well as one or more field programmable gate arrays (FPGAs), graphics processing units (GPUs), and / or application-specific integrated circuits (ASICs), which may be implemented, for example, on one or more cards or boards. Processors may include, for example, one or more microprocessors, microcontrollers, central processing units (CPUs), digital signal processors (DSPs), graphics processing units (GPUs), application-specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), and / or programmable logic controllers (or programmed logic controllers (PLCs)), etc. Memory may include, for example, one or more read-only memory (ROM), random access memory (RAM), EEPROM, flash memory, and / or registers, etc. Other non-transitory storage media may include, for example, one or more of magnetic disks and associated magnetic disk drives, optical disks and associated optical disk drives, and / or solid-state drives (SSDs), and the like.

[0142] Although not shown, analog transducer signals are received from an ultrasound probe or transducer array 206 (FIG. 2). The received analog transducer signals have a center frequency, for example, a center frequency of 2.76 MHz. Optionally, the received analog transducer signals are digitized, for example, via an analog-to-digital converter (not shown).

[0143] At 502, the receive section 210 (FIG. 2) of the ultrasound system 204 beamforms incoming frames of received RF data (e.g., incoming frame raw sample data). The receive section 210 may process incoming frame raw sample data received via an ultrasound probe or transducer, for example.

[0144] At 504, the receive section 210 (FIG. 2) of the ultrasound system 204 beam maps the incoming beams into a specified or otherwise defined format. The receive section 210 may, for example, map the received ultrasound signals into a frame stream buffer of the specified format.

[0145] At 506, an ensemble canceller in the receive section 210 (FIG. 2) of the ultrasound system 204 applies mean cancellation and depth-based gain to the beam-mapped RF data, e.g., to remove the mean to make differences more apparent.

[0146] At 508, the receive section 210 (FIG. 2) of the ultrasound system 204 performs RF division (or RF splitting) to separate non-ensemble beams (e.g., beams without a specified pulse pattern) from ensemble beams (e.g., beams with a specified pulse pattern) and result in multiple sets of RF data, e.g., multiple sets of ensemble beam RF data and a set of non-ensemble beam RF data. The output may include, for example, two sets of ensemble beam RF data (referred to as D-beam path 1 and D-beam path 2) and a set of non-ensemble beam RF data (referred to as B-beam). The set of ensemble beam RF data may primarily represent responses from markers (e.g., resonance or beat frequency responses), while the set of non-ensemble beam RF data may primarily represent structures (e.g., reflections from anatomical structures). Although the RF splitter is illustrated as having three legs providing two sets of ensemble beam RF data and one set of non-ensemble beam RF data, in other implementations the RF splitter may be implemented with a different number of legs. This may advantageously separate the B data from a final defined number (e.g., four) of ensemble beams. In some examples, such may be implemented or termed as RF detector filtering, for example, if RF detector filtering is enabled. The receive section 210 (FIG. 2) of the ultrasound system 204 may, for example, apply an FIR bandpass filter to separate ensemble beams (e.g., beams having a specified pulse pattern) from non-ensemble beams (beams lacking the specified pulse pattern).

[0147] The RF splitter output data is processed by three parts of the signal chain, which generally include parallel sets of operations performed on two sets of data, including the pulse ensemble response data and the B data. Operations in the parallel sets of operations are generally designated by a shared three-digit reference number followed by a lowercase letter "a," "b," and "c," respectively.

[0148] At 510a, 510b, 501C, the receive section 210 (FIG. 2) of the ultrasound system 204 performs RF mixing via RF mixers (RF Mixer D, Path 1, RF Mixer D, Path 2, and RF Mixer B) to generate RF direct quadrature (IQ) signals using a variety of different mixing frequencies and coefficients. The RF mixing (RF Mixer D, Path 1, RF Mixer D, Path 2) can result in two or more different multiples of the base or fundamental frequency of the ultrasound transmission (e.g., if the base or fundamental frequency is 2.76 MHz, then, for example, 1.5 times the base or fundamental frequency and 2 times the base or fundamental frequency). This may advantageously address possible "blinding effects" of outgoing ultrasound energy and / or improve the ability to identify which signals correspond to responses by the markers.

[0149] At 512a, 512c, 512c, the receive section 210 (FIG. 2) of the ultrasound system 204 optionally performs low-pass filtering via low-pass filters (D Low-pass Filter 1, D Low-pass Filter 2, and B Low-pass Filter 1, respectively), which may, for example, remove negative frequencies from the IQ signals.

[0150] At 514a, 514b, and 514c, the receive section 210 (FIG. 2) of the ultrasound system 204 demodulates the low-pass filtered RF IQ signals, for example, by performing envelope detection (D envelope detection 1, D envelope detection 2, and B envelope detection, respectively), which can advantageously remove the carrier signal and reconstruct the signal envelope, for example, converting the IQ signals back to an amplitude representation.

[0151] As also shown in FIGS. 5A-5C, the method 500 may further include performing B-log compression on the B data at 516, for example, to compress the data range to a desired range (e.g., 0-255).

[0152] 5A-5C, method 500 may further include performing sigma mapping on the results of D envelope detection 1 and D envelope detection 1 at 518. Method 500 may further include performing target detection at 520 using the sigma map generated by sigma mapping 518 and the B-log compressed data from B-log compression 516. Sigma mapping 518 and target detection 520 are described in more detail with reference to FIGS. 6A, 6B, and 7A-7D, respectively.

[0153] As also shown in FIGS. 5A-5C, the method 500 may further include performing detector decimation at 522, for example, to reduce the sample size in the detector beam.

[0154] As also shown in FIGS. 5A-5C, the method 500 may further include, at 524, providing the processed data to a D-scan converter or performing D-scan conversion on the data.

[0155] As also shown in FIGS. 5A-5C, the method 500 may further include performing B bilateral filtering at 526, for example, to smooth the R-Theta filter using an NxN kernel.

[0156] As also shown in FIGS. 5A-5C, the method 500 may further include performing B sample decimation at 528, for example, to reduce the samples in the beam.

[0157] As also shown in Figures 5A-5C, method 500 may further include performing focus mixing at 530 to combine the B focused beams and allow the detector beam to intersect the B data streams.

[0158] As also shown in FIGS. 5A-5C, the method 500 may further include performing scan conversion at 532, for example, to output a scan conversion suitable for visual presentation.

[0159] 6A and 6B show a method 600 for processing received ultrasound energy to identify responses from markers and provide visual and / or audible indications of the presence and / or location of the markers, particularly detailing the implementation of sigma mapping in the sigma phase, according to at least one illustrated embodiment. Method 600 may be implemented, for example, by the receive section 210 of ultrasound system 204 (FIG. 2).

[0160] Sigma Phase takes RF data split into multiple (e.g., two) bands centered around different multiples of the base or fundamental frequency (e.g., a first band centered around 1.5 times the base or fundamental frequency and a second band centered around 2 times the base or fundamental frequency). A set of roughly parallel operations is used for the two sets of data resulting from processing the outputs of two of the legs of the RF Split 508 (FIGS. 5A-5C).

[0161] In 602a, 602b, the receive section 210 of the ultrasound system 204 (FIG. 2) demodulates the RF data, for example, by performing envelope detection on two different multiples of the base or fundamental frequency (e.g., 1.5 times the base or fundamental frequency and 2 times the base or fundamental frequency). Note that envelope detections 602a, 602b (D envelope detection 1, D envelope detection 2) were previously shown in FIGS. 5A-5C as envelope detections 514a, 514b, respectively, and are included again in FIGS. 6A and 6B simply to provide context for the method 600. Thus, envelope detections 602a, 602b may not strictly be considered part of the method 600 of sigma mapping in at least some implementations, but rather may be performed as a separate or upstream portion of the return signal processing chain that feeds into the sigma mapping portion of the return signal processing chain.

[0162] In 604a and 604b, the receive section 210 (FIG. 2) of the ultrasound system 204 employs or applies ensemble focus blends to blend transmit (tx) focus patterns for data obtained from envelope detection 602a, 602b. For example, once the envelope is detected, the receive section 210 (FIG. 2) of the ultrasound system 204 blends alternating focus depths (e.g., a first focus depth and a second focus depth) at a transition depth. Adding two or more depths together can eliminate some of the transmit noise. In current implementations, two focus depths are used because including additional focus depths significantly increases the time involved in ultrasound transmission, detection, and processing, thus imposing undesirable limitations on hand and ultrasound probe movement. Processing beyond this stage can be performed laterally for the same depth position.

[0163] At 606a and 606b, the receive section 210 (FIG. 2) of the ultrasound system 204 uses or applies a lateral canceller. A lateral canceller, for example, subtracts the average of other beams from each ensemble sample. For example, the lateral canceller subtracts the average of surrounding beams (e.g., four surrounding beams) from the active or "current" beam (i.e., the beam currently being processed). The lateral canceller has a window size (e.g., a window size of 5) set by an environment variable (referred to herein as VPM_LATERAL_CANCELER_WINDOW).

[0164] At 608a, 608b, the receive section 210 (FIG. 2) of the ultrasound system 204 determines or calculates a sum of differences. This can reduce two beams in an ensemble to one beam, for example, by taking the absolute difference at each position within the beam. This operation helps to extract temporal differences in the RF data.

[0165] At 610a, 610b, the receive section 210 (FIG. 2) of the ultrasound system 204 determines or calculates the lateral standard deviation (also called across beam standard deviation). For example, the receive section 210 calculates the standard deviation of multiple beams (e.g., three beams) surrounding the target or "current" beam. A window size (e.g., 3) is set by the environment variable VPM_LATERAL_WINDOW. This operation helps to extract spatial differences in the lateral plane.

[0166] At 612a, 612b, the receive section 210 of the ultrasound system (FIG. 2) combines the two streams in various ways, for example, the data can be squared to enhance the dynamic range of the variant responses.

[0167] At 614, the receive section 210 (FIG. 2) of the ultrasound system combines the received or detected ultrasound data streams (e.g., two streams, one at 1.5 times the base or fundamental frequency and the other at twice the base or fundamental frequency) in various ways. For example, the 1.5x and 2x data paths can be combined by multiplying each position in the beam.

[0168] At 616, the ultrasound system receive section 210 (FIG. 2) optionally employs or applies frame cancellation, for example, performing frame to frame cancellation and smoothing. Alternatively, frame cancellation can be disabled so that the data passes through this operation unchanged.

[0169] At 618, the receive section 210 of the ultrasound system (FIG. 2) optionally employs or performs logarithmic compression (also called log compression) on the data. Logarithmic compression may advantageously map the data to a particular range (e.g., a range of 0 to 235, where 235 equals 160 dB). In this example, the step size is 0.681 dB per step.

[0170] At 620, the receive section 210 (FIG. 2) of the ultrasound system provides a sigma map output (eg, sigma map) that is the output of the sigma mapping.

[0171] 7A-7D illustrate a method 700 for processing received ultrasonic energy to identify responses from markers and provide visual and / or audible indications of the presence and / or location of the markers, particularly detailing the implementation of target detection during a target detection phase, according to at least one illustrated embodiment. Method 700 may be implemented, for example, by receive section 210 (FIG. 2) of ultrasound system 204.

[0172] In summary, target detection may involve the execution of a target best-fit algorithm or process designed to isolate blobs that best match a set of target spatial criteria. The target best-fit algorithm or process operates on flattened sigma sector data (e.g., arranged in a 48x2640 matrix) to generate equal-sized connection and distance matrices. As the distance matrix is ​​input (or populated), positions within the matrix are set to negative culling codes that indicate why that position was invalid. At the end of the culling chain, a set of potential blob centroids and their left, right, top, and bottom extents remains. These centroids are then evaluated in a centroid reduce sequence to find the best-fit centroid. This centroid is then passed to a centroid track algorithm or process. The use of centroids is particularly advantageous in applications where markers are used to mark tissue for inspection, monitoring, resection, and / or ablation.

[0173] At 702, the receive section 210 (FIG. 2) of the ultrasound system 204 receives one or more sigma mappings. Sigma mappings are described above with reference to FIGS. 6A and 6B.

[0174] At 704, the receive section 210 (FIG. 2) of the ultrasound system 204 constructs, configures, or calculates a beam histogram (e.g., average, peak, maximum) for each of one or more beams. The beam histogram may be used to inform dynamic threshold / flooded sector assessment, if performed.

[0175] At 706, the receive section 210 (FIG. 2) of the ultrasound system 204 constructs, configures, or calculates a frame histogram (e.g., average, peak, maximum) for each of one or more frames. The frame histogram may be used to inform dynamic threshold / flooded sector assessment, if performed.

[0176] At 708, the receive section 210 (FIG. 2) of the ultrasound system 204 implements or applies an adaptive threshold to the data. For example, the receive section 210 may set all values ​​below a sigma threshold to zero (0). The sigma threshold may be set by a harmonic sigma threshold register. As an example, the sigma threshold may be 75, which is equivalent to 51.08 dB. The sigma threshold establishes the basis for establishing spatial connections. This value may be intentionally set lower than the expected target minimum to ensure that objects of greater size are measured, including objects that may have sub-regions that meet the target minimum.

[0177] At 710, the receive section 210 (FIG. 2) of the ultrasound system 204 performs or applies focus merge. Focus merge combines focus sets. For example, focus merge may take a set of data from a previous stage (e.g., 48x2640x2 data) and flatten the data to create a smaller flattened data set (e.g., 48x2640 data). This facilitates alternating split focus in at least one implementation by duplicating data for depth sets. Other implementations may be able to omit such and / or employ other approaches.

[0178] At 712, the receive section 210 (FIG. 2) of the ultrasound system 204 implements or applies a connectivity map. For example, the receive section 210 calculates horizontal and vertical connectivity information for each cell. The connectivity map establishes the left, right, top, and bottom connections (i.e., nearest neighbors in rows and columns) of active samples.

[0179] At 714, the receive section 210 (FIG. 2) of the ultrasound system 204 determines or calculates distances, e.g., RUD distances, to the blob edges of each cell. For example, the receive section 210 calculates the left, right, top, and bottom distances (i.e., distance in rows, distance in columns) from the active samples to the unconnected edges.

[0180] At 716, the receive section 210 (FIG. 2) of the ultrasound system 204 determines or calculates a smooth distance. For example, the receive section 210 (FIG. 2) may average the distance data in the left, right, up, and down directions to smooth out small gaps.

[0181] At 718, the receive section 210 (FIG. 2) of the ultrasound system 204 performs a sigma threshold cull to filter out any out-of-bounds regions. The receive section 210 may, for example, remove regions based on a sigma threshold. For example, the receive section 210 checks the positions in the range data where the left, right, top, and bottom distances are zero and sets the cull code accordingly. The receive section 210 then checks the positions in the sigma data for values ​​less than the target minimum sigma threshold and sets the cull code accordingly. The cull code may be a Boolean flag or value indicating a binary state of either cull or not cull.

[0182] At 720, the receive section 210 (FIG. 2) of the ultrasound system 204 performs a regions cull. The region cull can remove regions based on sigma content and B content, and is provided by the B processing chain 717 and B log compression 719. For example, the receive section 210 checks the positions of the range data where connections are too wide and sets the culling code accordingly. Also, for example, the receive section 210 checks the positions of values ​​in the B data that exceed a B threshold and sets the culling code accordingly.

[0183] At 722, the receive section 210 (FIG. 2) of the ultrasound system 204 performs an orphans cull. The orphans cull may remove blob orphans created in a previous stage. For example, the receive section 210 searches the region of interest (ROI) associated with the currently active position for positions that were previously culled for being overly large and sets a culling code accordingly, if any. The ROI is defined by the distance to the left, right, above, and below the active position. The receive section 210 searches for smaller ROIs and tracks multiple positions that were culled for being below a sigma threshold. The smaller ROIs are defined by a subrange of the distance to the left, right, above, and below the currently active position. A culling code is set if the ratio of culled positions to valid positions exceeds a threshold.

[0184] At 724, the receive section 210 (FIG. 2) of the ultrasound system 204 refines the distance calculation, e.g., recalculate the distance without the culled value. For example, the receive section 210 may step out from the active position in the left, right, up, and down directions, counting the number of steps in each direction until the culled value is reached. These counts are saved as the new left, right, up, and down distances for the active position.

[0185] At 726, the receive section 210 (FIG. 2) of the ultrasound system 204 evaluates the culled regions, e.g., filters out out-of-bounds regions. The receive section 210 may, for example, check the width (total horizontal distance) and height (total vertical distance) of the active position against a minimum size requirement. The minimum size requirement may, for example, be defined by a set of registers referred to herein as DT Target Min Width and DT Target Min Height. If the minimum size requirement is not met, the receive section 210 sets the culling code accordingly.

[0186] At 728, the receive section 210 (FIG. 2) of the ultrasound system 204 refines the distance again, e.g., recalculate the distance without the culled value. The receive section 210 may, for example, step out in the left, right, up, and down directions from the active position, counting the number of steps in each direction until the culled value is reached. These counts are saved as the new left, right, up, and down distances for the active position.

[0187] At 730, the receive section 210 (FIG. 2) of the ultrasound system 204 performs a first pass of centroid reduction. The receive section 210 may, for example, reduce a distance set to the best match within a specified range. For example, the receive section 210 may calculate a width ratio, a height ratio, and an area / distance product for each valid centroid. The receive section 210 may recursively compare pairwise values ​​until reduced to a single best fit.

[0188] At 732, the receive section 210 (FIG. 2) of the ultrasound system 204 performs a second pass of centroid reduction. The receive section 210 may, for example, again reduce the set to the best matches within a specified range.

[0189] At 734, the receive section 210 (FIG. 2) of the ultrasound system 204 performs centroid tracking, generating, for example, a centroid tracking table or other data structure. The receive section 210 may obtain a sigma matrix and a distance matrix along with the best-fit centroid and track the blob over time (e.g., frame-to-frame). The receive section 210 may maintain a state machine that updates target tracking attributes across various states, for example, two main states: search and track. Within each primary state, there may be sub-states that control, for example, responsiveness, persistence, and reliability. The primary states and associated operations are discussed below.

[0190] At 736, the receive section 210 (FIG. 2) of the ultrasound system 204 performs or applies centroid merging. The centroid merging may be used to format and / or route desired data for display. In a standard mode of operation, the centroid merging may route isolated best-fit blobs with targeting accents (e.g., crosshairs, shadows), but may also route distance data, culling codes, test patterns, etc. The receive section 210 may update the centroid tracking table accordingly.

[0191] At 738, the receive section 210 (FIG. 2) of the ultrasound system 204 may perform one or more decimations to reduce the size of the data set. For example, the receive signal processing chain 402 may decimate the output data in preparation for scan conversion.

[0192] As mentioned above, there can be two main states: seeking and tracking.

[0193] In the search state, the receiver section 210 attempts to detect the same target multiple times, for example, three consecutive frames. This increases the level of confidence in a single detection. While three consecutive frames are provided as an example, a greater or lesser number of frames may be used. However, three frames is believed to provide a good balance between speed and accuracy. A consecutive detection is considered if the centroid of each subsequent detection is within the target range of the target in the previous frame. A consecutive detection counter is incremented with each successful detection. In response to a specified number of detections (e.g., three) of the same target occurring, the initial tracking attribute is set and the state machine transitions to the tracking state. The consecutive detection counter is reset immediately after a frame in which no target is detected.

[0194] In the tracking state, the receiving section 210 determines whether the target is within a target tracking region of interest (ROI).

[0195] If the target is within the target tracking ROI, the receiving section 210 updates the tracking attribute and the state of the state machine remains as tracking.

[0196] On the other hand, if the target is not within the target tracking ROI, the receiving section 210 executes the following algorithm.

[0197] The receive section 210 increments a set of persistence counters (called the ROI persistence counter and the Precise persistence counter).

[0198] The receiving section 210 determines whether the target is a reliable (e.g., Level 2) detection. If reliable, the receiving section 210 updates the tracking attributes for the new target and the state of the state machine is maintained as tracking.

[0199] The receive section 210 then enters the outer loop while the ROI persistence counter is less than or equal to zero.

[0200] The receive section 210 then enters an inner loop while the precision persistence counter is less than or equal to zero.

[0201] The receiving section 210 then clears the current target tracking attributes (Clear TARGET_CURRENT Tracking Attributes) and transitions the state machine to the tracking lost state.

[0202] When the ROI persistence counter becomes greater than zero (0), the receive section 210 exits the outer loop, clears the tracking attribute, and changes the state of the state machine to the search state.

[0203] Tracking attributes may include, for example, target confidence and target tracking ROI. Target confidence is determined within centroid tracking by accumulating counters for all high sigma, e.g., positions greater than 125.957 dB, and non-zero sigma positions within the target's target reach. If the ratio of high sigma to non-zero sigma is greater than a threshold (e.g., 25%), the confidence is increased, for example, from 1 to 2. The target ROI is the full beamwidth of the sector and the exact top and bottom of the target plus the borders above and below.

[0204] The foregoing detailed description illustrates various implementations of devices and / or processes through the use of block diagrams, schematic diagrams, and examples. While these block diagrams, schematic diagrams, and examples include one or more functions and / or operations, those skilled in the art will recognize that each function and / or operation in these block diagrams, flow diagrams, and examples, individually and / or collectively, can be implemented by various forms of hardware, software, firmware, or virtually any combination thereof. In one implementation, the subject matter may be implemented via an application-specific integrated circuit (ASIC). However, it should be recognized that the implementations disclosed herein may equivalently be implemented, in whole or in part, in a standard integrated circuit, as one or more computer programs running on one or more computers (e.g., as one or more programs running on one or more computer systems), as one or more programs running on one or more processors (e.g., microprocessors), as firmware, or virtually any combination thereof, and that designing circuitry and / or writing code for software and / or firmware is well within the skill of one of ordinary skill in the art in light of this disclosure.

[0205] Those skilled in the art will recognize that many of the methods or algorithms described herein may employ additional acts, omit some acts, and / or perform acts in a different order than specified.

[0206] Additionally, those skilled in the art will appreciate that the mechanisms taught herein can be distributed as a program product in a variety of forms, and that the exemplary implementations apply equally regardless of the particular type of signal-bearing medium used to actually accomplish the distribution, including, but not limited to, recordable types of media such as floppy disks, hard disk drives, CD ROMs, digital tape, and computer memory.

[0207] The various implementations described above can be combined to provide further implementations. No. 15 / 559764, International Patent Application PCT / US2016 / 23492, U.S. Patent Application No. 62 / 483,274, U.S. Patent Application No. 62 / 645,677, U.S. Patent Application No. 15 / 946,479, International Patent Application PCT / US2018 / 26291, U.S. Patent Application No. 62 / 892,952, U.S. Patent Application No. 63 / 441,558, U.S. Patent Application No. 63 / 441,558, and U.S. Patent Application No. 63 / 525,280 are each incorporated by reference herein in their entirety. Aspects of the implementations may be modified, if necessary, to employ systems, circuits, and concepts from various patents, applications, and publications to provide further implementations.

[0208] These and other changes can be made to the implementations in light of the above detailed description. In general, in the following claims, the terms used should not be construed to limit the claims to the specific implementations disclosed in the specification and claims, but rather to include all possible implementations, along with the full range of equivalents to which such claims are entitled. Accordingly, the claims are not limited by this disclosure.

Claims

1. 1. A method of operating an ultrasound system having a transmit section and a receive section to detect at least the presence or absence of a response from a tissue marker, comprising: generating a set of drive signals via the transmit section of the ultrasound system; providing the set of drive signals to an ultrasonic probe having at least one ultrasonic transducer to cause the at least one ultrasonic transducer to emit ultrasonic energy as ensembles of pulses, each ensemble of pulses being emitted at a plurality of focal depths along a respective one of a plurality of beams; processing a series of return signals through a return signal processing chain of a receive section of the ultrasound system, the series of return signals representing ultrasonic energy detected by the ultrasound probe, and processing the series of return signals through the return signal processing chain includes performing target detection, the target detection comprising: generating a sigma map indicating frame-to-frame changes in the returned signal data; performing a target best-fit process based at least in part on the sigma map to detect the presence or absence of a response signal from the tissue marker.

2. 2. The method of claim 1, wherein processing the series of return signals through the return signal processing chain includes mixing the return signals with a first multiple of a mixing frequency and mixing the return signals with a second multiple of a mixing frequency, the second multiple being different from the first multiple.

3. 2. The method of claim 1, wherein processing the series of return signals through the return signal processing chain includes mixing the return signals with a first multiple of a fundamental frequency of the ultrasonic waves and mixing the return signals with a second multiple of the fundamental frequency of the ultrasonic waves, the second multiple being different from the first multiple.

4. 4. The method of claim 3, wherein mixing the return signal with a first multiple of the fundamental frequency of the ultrasonic waves comprises mixing the return signal with a multiple of 2, and mixing the return signal with a second multiple of the fundamental frequency of the ultrasonic waves comprises mixing the return signal with a multiple of 1.

5.

5. 5. The method according to claim 2, wherein the step of processing the series of return signals through the return signal processing chain further comprises filtering the return signals resulting from the mixing with the first and second multiples to at least partially filter out ultrasonic waves emitted by the at least one ultrasonic transducer.

6. 3. The method of claim 2, wherein processing the series of return signals through the return signal processing chain includes performing envelope detection on each signal resulting from the mixing with the first multiple of the mixing frequency and the mixing with the second multiple of the mixing frequency.

7. The method of claim 1 , wherein generating a sigma map comprises performing sigma mapping to identify changes in the return signal data.

8. The method of claim 7 , wherein performing sigma mapping comprises performing a frame-to-frame comparison to identify changes in the received ultrasound data from frame to frame.

9. The method of claim 8 , wherein performing sigma mapping further comprises one or more of ensemble focus blending, lateral canceling, sum of differences, determining lateral standard deviation, and squaring.

10. 10. The method of claim 9, wherein performing sigma mapping further comprises any one or more of multiplying two streams of ultrasound data and performing frame cancellation.

11. 11. The method of claim 1, wherein the step of performing a target best-fit process comprises performing a best-fit process to identify a blob that best matches a set of target spatial criteria.

12. The method of claim 11 , wherein performing target detection includes generating a beam histogram and generating a frame histogram.

13. The method of claim 10 , wherein performing target detection includes applying an adaptive threshold.

14. The method of claim 10 , wherein performing target detection includes performing focus merging to combine sets of ultrasound data from two or more focus levels.

15. The method of claim 10 , wherein performing target detection includes generating connectivity map data representing connectivity information between cells along at least two axes, the at least two axes being perpendicular to each other.

16. 11. The method of claim 10, wherein performing target detection includes at least one of calculating a distance to a blob edge for each cell of the plurality of cells and smoothing the calculated distance by filtering out out-of-boundary regions.

17. 11. The method of claim 10, wherein performing target detection includes any one or more of: performing a sigma threshold cull by removing regions based on a sigma threshold; performing a region cull by removing regions based on sigma and B content; and performing an orphan cull by removing blob orphans.

18. The method of claim 10 , wherein performing target detection includes recalculating distances without culled values.

19. 11. The method of claim 10, wherein performing target detection includes any one or more of determining blob centroids, performing centroid reduction, performing centroid tracking, and performing centroid merging.

20. 20. The method of any one of claims 1 to 4, or 6 to 10, or 13 to 19, wherein processing the series of return signals through the return signal processing chain includes any one or more of performing focus mixing and scan conversion.

21. 21. The method of claim 20, wherein processing the series of return signals through the return signal processing chain further comprises visually and / or audibly presenting marker localization information.

22. 22. The method of claim 21, wherein visually and / or audibly presenting the marker localization information comprises presenting a visual representation of the center of gravity of the marker relative to a visual representation of the anatomical structure.

23. 22. The method of claim 21, wherein visually and / or audibly presenting marker localization information comprises presenting an auditory representation of movement of the ultrasound probe relative to a marker's center of gravity.

24. generating a set of drive signals via the transmit section of the ultrasound system, generating a drive signal having a nominal pulse repetition frequency; introducing a power magnitude variation between at least some pulses of the ensemble of pulses of the drive signal; and supplying the drive signal to the at least one ultrasonic transducer, the drive signal introducing the power magnitude fluctuations, to cause the at least one ultrasonic transducer to emit the ultrasonic signal having the power magnitude fluctuations.

25. Generating a set of drive signals via the transmit section of the ultrasound system comprises: generating a drive signal having a nominal pulse repetition frequency; introducing variations from one or more of the amplitude, fundamental frequency, or pulse repetition frequency of the drive signal; and supplying the drive signal to the at least one ultrasonic transducer, the drive signal introducing the fluctuation, to cause the at least one ultrasonic transducer to emit an ultrasonic signal having the fluctuation.

26. a transmit section that generates and supplies a set of drive signals to an ultrasonic probe having at least one ultrasonic transducer to cause the at least one ultrasonic transducer to emit ultrasonic energy as ensembles of pulses, each ensemble of pulses being emitted at a plurality of focal depths along a respective one of a plurality of beams; and a receive section for processing a series of return signals according to the method of any preceding claim, the series of return signals representing ultrasonic energy detected by the ultrasonic probe.

27. 27. The ultrasound system of claim 26, wherein the transmit section generates and provides a set of drive signals according to the method of claim 25.

28. a transmit section that generates and supplies a set of drive signals to an ultrasonic probe having at least one ultrasonic transducer to cause the at least one ultrasonic transducer to emit ultrasonic energy as ensembles of pulses, each ensemble of pulses being emitted at a plurality of focal depths along a respective one of a plurality of beams; 1. An ultrasound system comprising: a receive section including a return signal processing chain that processes a series of return signals, the series of return signals representing ultrasound energy detected by the ultrasound probe; and the return signal processing chain performing target detection, the target detection including generating a sigma map indicative of changes between frames of return signal data, and performing a target best-fit process based at least in part on the sigma map to detect the presence or absence of a response signal from a tissue marker.

29. 30. The ultrasound system of claim 28, wherein the return signal processing chain mixes the return signal with a first multiple of a mixing frequency and mixes the return signal with a second multiple of a mixing frequency, the second multiple being different from the first multiple.

30. 29. The ultrasound system of claim 28, wherein the return signal processing chain mixes the return signal with a first multiple of a fundamental frequency of the ultrasound and mixes the return signal with a second multiple of the fundamental frequency of the ultrasound, the second multiple being different from the first multiple.

31. 30. The ultrasound system of claim 28, wherein the return signal processing chain mixes the return signal with a multiple of 2 of the fundamental frequency of the ultrasound and mixes the return signal with a multiple of 1.5 of the fundamental frequency of the ultrasound.

32. 32. The ultrasound system of any one of claims 29 to 31, wherein the return signal processing chain further filters the return signal resulting from mixing with the first multiple and the second multiple to at least partially filter out ultrasound waves emitted by the at least one ultrasound transducer.

33. 30. The ultrasound system of claim 29, wherein the return signal processing chain performs envelope detection on each signal resulting from the mixing with the first multiple of the mixing frequency and the mixing with the second multiple of the mixing frequency.

34. 30. The ultrasound system of claim 28, wherein the return signal processing chain performs sigma mapping to generate a sigma map.

35. 35. The ultrasound system of claim 34, wherein to perform sigma mapping, the return signal processing chain performs a frame-to-frame comparison to identify changes in received ultrasound data from frame to frame.

36. 36. The ultrasound system of claim 35, wherein to perform sigma mapping, the return signal processing chain performs one or more of ensemble focus blending, lateral cancellation, sum of differences, lateral standard deviation determination, and squaring.

37. 37. The ultrasound system of claim 36, wherein the return signal processing chain further performs any one or more of: multiplication of two streams of ultrasound data; and frame cancellation to perform sigma mapping.

38. 38. The ultrasound system of claim 37, wherein to perform a best-fit process, the return signal processing chain performs a target best-fit process to identify the blob that best matches a set of target spatial criteria.

39. 38. The ultrasound system of claim 37, wherein the return signal processing chain generates a beam histogram and generates a frame histogram to perform target detection.

40. 38. The ultrasound system of claim 37, wherein the return signal processing chain applies an adaptive threshold to perform target detection.

41. 38. The ultrasound system of claim 37, wherein the return signal processing chain performs focal merging to combine sets of ultrasound data from two or more focal levels to perform target detection.

42. 38. The ultrasound system of claim 37, wherein to perform target detection, the return signal processing chain generates connectivity map data representing connectivity information between cells along at least two axes, the at least two axes being perpendicular to each other.

43. 38. The ultrasound system of claim 37, wherein to perform target detection, the return signal processing chain at least one of: calculating a distance to a blob edge for each cell of a plurality of cells; and smoothing the calculated distances by filtering out out-of-boundary regions.

44. To perform target detection, the return signal processing chain comprises: performing a sigma threshold cull by removing regions based on a sigma threshold; performing a region cull by removing regions based on Sigma and B content; performing orphanscull by removing blob orphans; 38. The ultrasound system of claim 37, further comprising:

45. 38. The ultrasound system of claim 37, wherein the return signal processing chain recalculates range without culled values ​​to perform target detection.

46. To perform target detection, the return signal processing chain comprises: Determining the centroid of the blob; Implementing a center of gravity reduction; performing centroid tracking; and performing a centroid merge; 38. The ultrasound system of claim 37, further comprising:

47. The ultrasound system of any one of claims 28-31 or 33-46, wherein the return signal processing chain performs any one or more of focus mixing and scan conversion.

48. 48. The ultrasound system of claim 47, wherein the return signal processing chain presents marker localization information visually and / or audibly.

49. 49. The ultrasound system of claim 48, wherein the return signal processing chain presents a visual representation of the center of gravity of the marker relative to a visual representation of the anatomy to present marker localization information visually and / or audibly.

50. 49. The ultrasound system of claim 48, wherein the return signal processing chain presents an auditory representation of the movement of the ultrasound probe relative to the center of gravity of a marker to visually and / or audibly present marker localization information.

51. To generate a set of drive signals, the transmit section of the ultrasound system: generating a drive signal having a nominal pulse repetition frequency; introducing a power magnitude variation between at least some pulses of the ensemble of pulses of the drive signal; supplying the drive signal, into which a power magnitude variation is introduced, to the at least one ultrasonic transducer to cause the at least one ultrasonic transducer to emit the ultrasonic signal having a power magnitude variation; 51. The ultrasound system of any one of claims 28 to 31 or 33 to 50.

52. To generate a set of drive signals, the transmit section of the ultrasound system: generating a drive signal having a nominal pulse repetition frequency; introducing variations from one or more of the amplitude, fundamental frequency, or pulse repetition frequency of the drive signal; providing the drive signal having the introduced variation to the at least one ultrasonic transducer to cause the at least one ultrasonic transducer to emit the ultrasonic signal having the variation; 51. The ultrasound system of any one of claims 28 to 31 or 33 to 50.

53. A marker for marking tissue, comprising: A gel body; a detectable object carried by the gel body, the detectable object being detectable via an imaging modality other than ultrasound; a plurality of ultrasound reflective elements carried by the gel body, the plurality of ultrasound reflective elements being carried in suspension when the gel body is hydrated, the ultrasound reflective elements being free to move in at least one dimension to an extent or distance sufficient to enhance any scattered return from the ultrasound reflective elements in response to ultrasonic interrogation of the marker.

54. 54. The marker of claim 53, wherein the plurality of ultrasound reflective elements carried in suspension are free to at least one of sway, vibrate, or preferably randomly move in at least two or more dimensions to an extent or distance sufficient to enhance any scattered return from the ultrasound reflective elements in response to ultrasound interrogation of the marker when the gel body is hydrated.

55. 54. The marker of claim 53, wherein the plurality of ultrasound reflective elements carried in suspension, when the gel body is hydrated, are free to move with varying speeds to an extent or distance sufficient to enhance any scattered return from the ultrasound reflective elements in response to ultrasound interrogation of the marker.

56. 54. The marker of claim 53, wherein the plurality of ultrasound reflective elements are in a plurality of aggregates or clusters of ultrasound reflective elements while carried in suspension within the gel body.

57. 57. The marker of claim 56, wherein the plurality of aggregates or clusters of the plurality of ultrasound reflective elements carried in suspension, when the gel body is hydrated, are free to move with variation in velocity and a sufficient degree or distance to enhance any scattered return from the ultrasound reflective elements in response to ultrasound interrogation of the marker.

58. 54. The marker of claim 53, wherein the gel body comprises or consists of a hydrogel.

59. 54. The marker of claim 53, wherein the gel body comprises or consists of a natural hydrogel.

60. 54. The marker of claim 53, wherein the gel body comprises or consists of an artificial hydrogel.

61. 54. The marker of claim 53, wherein the gel body is at least partially crosslinked.

62. 62. The marker of claim 61, wherein the degree of cross-linking of the gel body causes the ultrasound reflective elements to freely swing, vibrate, or preferably randomly move relative to one another in at least two or more dimensions to a degree or distance sufficient to enhance any scattered return from the ultrasound reflective elements in response to ultrasound interrogation of the marker.

63. 54. The marker of claim 53, wherein the plurality of ultrasound reflective elements consist of or include a plurality of porous or mesoporous hollow shells, each of the porous or mesoporous hollow shells having a primary cavity and a plurality of pores in fluid communication with the cavity.

64. 54. The marker of claim 53, wherein the plurality of ultrasound reflective elements consist of or comprise a plurality of porous or mesoporous particles, each of the porous or mesoporous particles comprising a plurality of pores isolated from one another.

65. 54. The marker of claim 53, wherein the plurality of ultrasound reflective elements consist of or include silica.

66. 54. The marker of claim 53, wherein the plurality of ultrasound reflective elements are dispersed throughout the gel body, for example in a colloidal dispersion or suspension throughout the gel body.

67. 54. The marker of claim 53, wherein the plurality of ultrasound reflective elements are dispersed throughout the gel body in a colloidal dispersion.

68. A marker according to any one of claims 53 to 67, wherein each of the plurality of ultrasound reflective elements has an irregular surface.

69. 69. The marker of claim 68, wherein each of the plurality of ultrasound reflective elements contains gas within pores or cavities of the ultrasound reflective element.

70. 70. The marker of claim 69, wherein each of the plurality of ultrasound reflective elements includes a hydrophobic coating that prevents ingress of liquid into the pores or cavities thereof.

71. 71. The marker of claim 70, wherein each of the plurality of ultrasound reflective elements includes a hydrophobic coating that prevents ingress of liquid into the pores or cavities thereof.

72. 72. The marker of claim 71, wherein the hydrophobic coating prevents the ingress of liquid into the pores or cavities for an extended period of at least 9 months.

73. 69. The marker of claim 68, wherein the gel body is at least one of dehydrated and freeze-dried prior to implantation into body tissue.

74. 69. The marker of claim 68, wherein the gel body forms a framework for bioadhesion via the natural healing process of the body tissue into which the marker is implanted.

75. 54. The marker of claim 53, wherein a combination of surface roughness, material properties of the material comprising the ultrasound reflecting elements, porosity of the ultrasound reflecting elements, gas trapped by the ultrasound reflecting elements, size of the ultrasound reflecting elements, size of aggregates or clusters of ultrasound reflecting elements, and their degrees of freedom of movement enhances the backscatter response to ultrasound.

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