Tissue marker detection systems and methods employing ultrasound and tissue markers

Abstract

Ultrasound systems and methods emit broadband ultrasound through a probe to excite and detect markers in body tissue (e.g., mammary gland, lung). The returned ultrasound energy (narrow band) detected by the probe is processed to differentiate the response of the marker from other detected ultrasound. The process is fast enough to accommodate movement that is typically a handheld probe, while providing accurate positioning. The processing may include RF filtering and mixing, demodulation, and target detection by spatial or "image" processing based on the known geometry of the marker and its response characteristics. Target detection may include sigma mapping with frame-to-frame comparisons, and target best fit processing to separate speckles that best match a set of target space criteria. Optionally, nonlinearity is introduced into the ultrasound emission and used to identify the response of the marker. The marker can suspend and move in the hydrogel.

Description

[0001] Cross-references to related applications

[0002] 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, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This disclosure generally relates to the detection of markers (e.g., tissue markers) and markers in body tissues, particularly to markers whose detectability is enhanced by ultrasound (e.g., color Doppler ultrasound), and systems and methods for using ultrasound to detect markers, such as during surgery, which can, for example, facilitate the detection of the edges of body tissue (e.g., abnormal body tissue) to be monitored, biopsied, removed, or ablated. Background Technology

[0004] Description of Related Art

[0005] Various types of markers are used to label body tissue that needs to be monitored over time, or body tissue that has been biopsied, removed, or ablated. For example, some markers can allow or enhance visual detection, such as by a surgeon during surgery. Some markers can be detected by various types of energy emission imaging modalities, such as radiological imaging like ultrasound, X-ray imaging, computed tomography (CT), computed axial computed tomography (CAT), or magnetic resonance imaging (MRI). These different imaging modalities are often used by different clinicians or technicians in different scenarios, and markers detectable under various visual detection or imaging modalities often require different physical properties to be detected.

[0006] Some markers may be permanent, while others may be absorbed by the body over time. For example, it may be useful to mark a portion of body tissue for a considerable period of time (e.g., months or a year) for subsequent evaluation or testing. Summary of the Invention

[0007] The applicant has developed multimodal markers that can be detected by ultrasound or other imaging modalities (such as X-ray, MRI and / or other imaging techniques), and that can be selectively absorbed over time and can last for a long period of time (e.g., approximately 9 months).

[0008] Markers for body tissue come in a variety of forms, and can include a plurality of ultrasound-reflective elements and one or more gels (e.g., hydrogels) that incorporate the ultrasound-reflective elements. For example, the ultrasound-reflective elements can take the form of porous or mesoporous particles or porous or mesoporous voids. The cavities and / or pores (e.g., voids, porous or mesoporous particles) of the ultrasound-reflective elements can be filled with a fluid (e.g., a gas (e.g., air), a liquid, or a combination of a gas and a liquid (e.g., a vapor)), and can advantageously optionally be free of perfluorocarbons. The ultrasound-reflective elements can be coated, e.g., with a hydrophobic coating, to at least temporarily seal the pores to prevent or delay the ingress of liquid into the cavities to the interior of the ultrasound-reflective elements (e.g., voids, porous or mesoporous particles).

[0009] The ultrasound-reflective elements can include or consist of one or more forms of silica. The gels (e.g., hydrogels) can be natural gels (e.g., gelatin), or artificial gels (e.g., polyethylene glycol (PEG)), or the markers can consist of natural and artificial gels (e.g., natural and artificial hydrogels). The gels can be partially or fully cross-linked. The gels (e.g., hydrogels) can be designed to be absorbed by the body over a period of time, or can be non-absorbable.

[0010] The markers can optionally include contrast elements or "contrast agents" to allow the markers to be detected by one or more imaging modalities in addition to ultrasound. For example, the markers can include one or more radiopaque materials (e.g., metals, gold, platinum, tantalum, bismuth, barium, etc.) to allow the markers to be detected by X-ray imaging. For example, the markers can include metal elements in the form of clips (e.g., metal wires with defined shapes (e.g., helically wound metal wires)), strings, or coils, or a plurality of metal particles. Also for example, the markers can include one or more MRI imaging contrast materials (e.g., gadolinium, including compounds such as gadolinium-DTPA, ferrous gluconate, ferrous sulfate, etc.) to allow the markers to be detected by MRI imaging. Also for example, the markers can include one or more dyes (e.g., fluorescent dyes, methylene blue) to make the markers more easily detected visually.

[0011] There is a need for improved imaging techniques, e.g., improved ultrasound imaging techniques, that do not use ionizing radiation, which can enhance detection of markers in body tissue and / or detection of the margins of certain body tissue (e.g., abnormal body tissue (e.g., tumors) or body tissue suspected of being abnormal) that is marked with implanted markers. This can advantageously allow marker localization in surgical scenarios where ionizing radiation sources can not be readily available or can not be desirable or convenient to use.

[0012] There is also a need for improved markers, e.g., tissue markers that are more easily detected in body tissue.

[0013] The present disclosure generally relates to the detection of markers in bodily tissue, and also to systems and methods that, for example, can employ ultrasound processing to facilitate more accurate detection of tissue to be monitored, biopsied, resected, or ablated, as compared to using conventional methods. 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 are particularly well suited for use in surgery, for example, by a surgeon or other non-specialized or specialized medical imaging technician or non-specialized or specialized ultrasound technician. Thus, it is particularly advantageous if the operation of the systems and methods is simplified, for example, does not require manual adjustment of settings or input of parameters by the operator (e.g., surgeon). Additionally, it is particularly advantageous if the operation of the systems and methods accommodates the motion of the operator’s hand holding the probe (e.g., ultrasound probe), for example, accommodating imprecise and / or rapid or uneven motion (e.g., varying speed) of the probe, which is typically not a skilled or specialized ultrasound technician. It is further particularly advantageous if the operation of the system provides accurate localization in at least a two-dimensional area, preferably in a three-dimensional volume, for example, using visual and / or audible indications or alerts. It is even particularly advantageous if the system provides accurate results such that false results (e.g., false detection or false alert; missing a marker when a marker is present) are rare or even nonexistent. User feedback can be provided visually (e.g., representation of the marker or crosshairs relative to an anatomical image) and / or audibly (e.g., audible alert when the probe is moving in one, two, or even three dimensions toward or away from the marker).

[0014] The present disclosure also generally relates to markers (e.g., tissue markers) having physical properties that make the markers more easily distinguishable by 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-reflective elements (e.g., porous or mesoporous particles; porous or mesoporous voids) suspended in the gel body. For example, the ultrasound-reflective elements can be dispersed throughout the gel body, for example, in a colloidal dispersion or colloidal suspension.

[0015] The gel body can take the form of a hydrogel (e.g., natural hydrogel, artificial hydrogel, combination of natural and artificial hydrogel). The gel body can be fully or partially cross-linked, so long as the ultrasound-reflective elements can move (e.g., vibrate or oscillate, preferably randomly move) freely in at least one dimension (e.g., along at least one axis, preferably along two or more axes) to a sufficient degree or distance when the gel body is hydrated to enhance any scattered returns (e.g., backscatter) from the ultrasound-reflective elements in response to ultrasound interrogation of the marker, preferably with changes in velocity of the ultrasound-reflective elements and / or changes in aggregates or clusters of the ultrasound-reflective elements.

[0016] The ultrasound-reflecting element typically has an irregular surface that results in scattering (e.g., backscattering) in response to ultrasound interrogation of the marker. The ultrasound-reflecting element typically contains a fluid (i.e., a gas, a liquid, or a combination of a gas and a liquid, although typically a gas (e.g., air or an inert gas)), which enhances backscattering in response to ultrasound interrogation of the marker. The ultrasound-reflecting element typically includes a hydrophobic coating (e.g., silicone), which prevents liquid from entering the pores, cavities, or interior of the ultrasound-reflecting element for an extended period of time (e.g., 3 months, 9 months, 18 months, or even longer), even if the marker is subjected to bodily fluids for an extended period of time. This advantageously prevents the ultrasound-reflecting element from being reduced or even eliminated from detectable scattering due to “wetting.”

[0017] The gel body can be dehydrated or freeze-dried until implanted in the body tissue, and then the gel body will hydrate over time as fluid (e.g., water) is absorbed from the body tissue. The gel body also provides a framework for bioadhesion through the natural healing process of the body tissue in which the marker is implanted. This can secure the marker in place in the body tissue without the use of glue or adhesive.

[0018] The various described physical structures or physical properties of the marker provide or enhance scattering (e.g., backscattering) of ultrasound from the marker, particularly resulting in a wide velocity spectrum, whether single or aggregated or clustered, that greatly facilitates detection using color Doppler ultrasound technology.

[0019] The ultrasound system (e.g., hardware, software, firmware) employs excitation and detection algorithms to discern the response of the marker and provide a direct indication (not itself representing a unique visual indication of the body tissue, a unique audible alert). This is a very different approach compared to commercial off-the-shelf ultrasound systems. While a trained clinician can use the images of traditional color Doppler to locate a marker in tissue, the approach described herein allows for a faster acquisition, no manual manipulation, a set-up free user experience. In contrast, traditional ultrasound requires a trained clinician to adjust the settings of the ultrasound machine. Traditional ultrasound is an interpretive visual activity, requiring a trained clinician to visually interpret the displayed ultrasound images. In the approach described herein, the ultrasound system alerts the clinician in real-time whether a marker is found and the location of that marker in the tissue. Thus, the clinician receives what can be characterized as a binary answer (e.g., a visually unique and audibly present indication when a marker is located) and automatic ranging (e.g., distance and direction relative to the current location) whereas the clinician must try to interpret the anatomy in the ultrasound images. With the approach described herein, there is no need to fiddle with knobs or clinician adjustment of settings, just a quick, easy detection with a direct manipulation that does not disrupt the normal workflow of the operating room. This is particularly important in a surgical environment where the patient is under anesthesia, in a sterile environment, and where the clinician is typically a surgeon who can not have the experience using ultrasound as an ultrasound technician would, and is busy with other aspects of the surgery.

[0020] Unlike traditional approaches that focus ultrasound energy in a specific region of interest (ROI), in the approach described herein, the transmit beam model disperses energy throughout the interrogated space. The GPU algorithm advantageously implements a parallel processing signal path analysis in the receive beam model to distinguish the response from the marker from all other detected signals and noise.

[0021] The detection imaging system is designed to help a clinician (e.g., a surgeon) find an implanted tissue marker (e.g., View Point Medical’s OneMark TMThe system is used to scan and locate an implanted marker in body tissue (e.g., breast tissue, lung tissue). The system emits pulsed ultrasound energy to excite the marker and then compares the motion changes between sets of pulses from the received ultrasound energy (e.g., a return signal or series of return signals, which can constitute ultrasound energy scattering or backscatter returns from the marker or a portion of the marker). The pulses cause greater changes at the location where the marker is placed compared to the energy levels of the unmarked region. The system highlights the marker location on a display screen (e.g., a liquid crystal display (LCD)), for example, by superimposing a color map on a low resolution gray scale representation of the anatomy. The system additionally or alternatively uses additional audio and visual feedback to indicate the location of the marker, for example, an X-Y crosshair centered on the marker in a low resolution gray scale representation of the anatomy.

[0022] Generally, surgeons will look for a center marker in order to perform a resection around the marker and get reasonable confirmation that they have performed the correct resection. The system supports current standard of care for lesion localization and provides more visual information than the non-visual display marker wireless localization devices currently in use. The presently described system and method can generate localization information that advantageously represents the marker centroid (e.g., visually with a crosshair) compared to the sound or wire center of a tag, and can demonstrate real-time imaging centering of the marker, which is particularly advantageous in a surgical setting.

[0023] The scanning process applies a non-diagnostic, customized, ultrasound-based method to excite the marker and provide real-time images of the marker location in the skin surface and wound during resection for the clinician (e.g., surgeon). Unlike traditional diagnostic ultrasound imaging, the system does not need to provide any qualitative information from the scan other than the marker for which the system is designed to detect. Unlike ultrasound systems that aim to display all structural features of the tissue, OneMark TM The system optionally and preferably does not provide diagnostic ultrasound modes, does not serve as a tool for tissue qualitative analysis, and does not provide adjustment controls like a diagnostic tool. The system can be used to image the marker location to provide information to aid in clinical localization. The system advantageously requires little setup and is designed to be used by surgeons who are not specialized ultrasound technicians and by surgeons who do not typically operate ultrasound equipment in their daily practice. It is designed to maximize ease of use by automating the marker imaging process, eliminating buttons and / or keys or a keyboard, and better accommodating sterile field applications. The system also advantageously supports fast marker detection to effectively support the clinician in treating the patient under anesthesia.

[0024] In contrast to most ultrasound systems for diagnostics that attempt to focus the transmitted ultrasound energy to a point of interest, the presently described ultrasound systems and methods spread the transmitted broadband ultrasound energy to an entire region of interest (e.g., an entire breast, an entire lung) in at least one mode. Thus, unlike in diagnostic ultrasound where one attempts to increase resolution, the presently described ultrasound systems and methods attempt to achieve high, even optimal, power coupling to the marker. Ultrasound can be transmitted as integrated pulses along various axes, angles, or beams, each of which is associated with a corresponding piezoelectric element, crystal, or transducer of the ultrasound probe. Unlike most ultrasound systems for color Doppler, which employ a relatively low frame rate with a relatively high number of pulses per set, the presently described ultrasound systems and methods generally employ a relatively high frame rate and a relatively low number of pulses per set (e.g., 3, 4, 5), and generally also employ a relatively small number of focal depths (e.g., 2), all in an effort to achieve sufficient speed to accommodate the expected hand motion of the ultrasound probe. For example, when operating in color Doppler mode, the presently described ultrasound systems and methods can use a set of 5 pulses on each beam and at 2 different focal depths. For example, when operating in B mode, the presently described ultrasound systems and methods can use a set of 4 pulses on each beam.

[0025] The presently described ultrasound systems and methods employ transmitted pulsed ultrasound to move echogenic material (e.g., silica particles with entrapped fluid) in a hydrogel, e.g., to oscillate the echogenic material at a resonant frequency or beat frequency. The presently described ultrasound systems and methods employ this oscillation in identifying or localizing a marker, e.g., examining received ultrasound (e.g., a return signal or series of return signals, which can constitute a scattering or backscattering return of ultrasound energy from a marker or portion of a marker) to determine relatively large motion from frame to frame as compared to background features, which generally indicates an oscillating marker. Thus, the system attempts to deliver or “pump” enough energy to the echogenic material to induce oscillation. This oscillation can manifest as a flicker or sparkle effect in a color mode of ultrasound imaging. Increasing the applied energy can 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. It can be desirable to have some gap between integrated pulses, e.g., to provide some margin in the ultrasound probe, although the repetition of pulses should be close enough to maintain oscillation of the echogenic material.

[0026] Notably, the more pulses in the set, the longer the time required to emit, receive, and process the ultrasound. This, combined with the reliance on identifying the marker's response in multiple consecutive frames to accurately determine the marker's position, and the fact that the ultrasound probe is typically handheld and will move, places constraints on the technical operation, including the emission pattern, frame rate, and receive signal processing chain. Moreover, while the relatively large amplitude (e.g., voltage) of the emitted ultrasound pulses can facilitate detection of the marker's response, practical considerations can place limits on it. For example, thermal limits of the piezoelectric elements, crystals, or transducers or ultrasound probe head, and limits on the amplitude of the emitted ultrasound pulses that can be used.

[0027] The presently described ultrasound systems and methods employ a receive signal processing chain to process the return signal or series of return signals, which can constitute scattering or backscattering returns of ultrasound energy from a marker or portion of a marker. The receive signal processing chain can include one, more, or all of: RF filtering and mixing, demodulation and envelope detection, and target detection by spatial or "image" processing based on the known geometry of the marker and its response characteristics. The target detection can include sigma mapping with frame-to-frame comparison, and target best-fit processing to isolate the spot that best matches a set of target spatial criteria. The processing is fast enough to accommodate movement of a typically handheld probe while providing accurate localization.

[0028] In some embodiments, a system (e.g., an ultrasound system) advantageously introduces nonlinearity in the drive signal, thereby generating nonlinearity in the ultrasound emission or interrogation signal. The nonlinearity can generate a nonlinear response or return from the tissue marker (e.g., from an echogenic portion of the tissue marker), thereby facilitating detection (e.g., matched filtering) of the tissue marker by the ultrasound system. Preferably, the nonlinearity can take the form of a change in the amplitude (e.g., voltage) of the ultrasound emission or interrogation signal. Additionally or alternatively, the nonlinearity can be introduced by changing the frequency or phase of the ultrasound emission or interrogation signal from a nominal frequency or nominal phase. For example, a change can be introduced in the fundamental or base frequency of the output ultrasound emission, and / or a change can be introduced in the pulse repetition frequency of the output ultrasound emission. The nonlinearity can be periodic, can form or follow a defined pattern, or can be pseudorandom or random.

[0029] In some embodiments, systems (e.g., ultrasound systems) and methods advantageously introduce a magnetic field into body tissue. This can be suitable for enhancing detection of a marker in certain body tissue (e.g., lung tissue having a large amount of air), and is useful for suitable markers (e.g., tissue markers including iron metal and / or ferrous oxide). The system can generate the magnetic field by passing an electrical current through an electrical conductor (e.g., an antenna, a coil antenna, a closed loop antenna). The electrical conductor can be carried by or otherwise part of an ultrasound probe, for example. The magnetic field can be periodic, can form or follow a defined pattern, or can be pseudo-random or random. The magnetic field can oscillate, which can cause the marker or a portion of the marker to oscillate or vibrate, for example at a resonant frequency or to generate a beat frequency. The outputted ultrasound emissions can be imposed on top of the magnetic field. In some embodiments, the ultrasound waves received by the receiving portion (e.g., a return signal or series of return signals) can be synchronized with the emission of the magnetic field. The use of the magnetic field can advantageously facilitate detection of ultrasound echoes from the tissue marker (e.g., from an echogenic portion of the tissue marker). BRIEF DESCRIPTION OF DRAWINGS

[0030] In the drawings, like reference numerals refer to like elements or acts throughout. 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 can have been exaggerated or distorted to improve readability of the drawings. In addition, the specific shapes and angles of the elements are not intended to convey any particular information other than to assist in the understanding of the present disclosure, and the present disclosure should not be limited to the specific shapes and angles shown.

[0031] FIG. 1A is an isometric view of a marker for marking body tissue and a distal portion of an instrument that can selectively implant the marker in a desired location in the body tissue, according to one illustrated embodiment, the marker including a persistent (e.g., long-term) portion and two additional fast dissolving portions.

[0032] FIG. 1B is an isometric view of a marker, according to one illustrated embodiment, the marker can for example take the form of a persistent (long-term) portion FIG. 1A including a gel (e.g., hydrogel) carrier, a plurality of ultrasound reflective elements, a clip, wire or coil detectable by x-ray imaging, and an optional contrast agent to enhance detection by imaging modalities other than ultrasound, an enlarged detail view showing one of the plurality of aggregates or clusters of ultrasound reflective elements in detail.

[0033] FIG. 2is a schematic diagram of an ultrasound system according to at least one illustrated embodiment, wherein an ultrasound transducer is positioned relative to a marker that is ultrasound reflective and typically implanted in body tissue, the ultrasound imaging system is operable to cause a wideband ultrasound signal to be transmitted into the body tissue and to process received ultrasound energy to discern or identify a response from the marker and to provide a suitable visual and / or audible indication of the marker's presence and / or location.

[0034] FIG. 3 is a block diagram showing exemplary architecture of an ultrasound system according to at least one illustrated embodiment.

[0035] FIG. 4 is a block diagram showing exemplary receive signal chain of an ultrasound system according to at least one illustrated embodiment, and in particular detail of its receive signal processing chain.

[0036] FIG. 5A , FIG. 5B and FIG. 5C illustrates a method of processing received ultrasound energy to identify a response from a marker and to provide a visual and / or audible indication of the marker's presence and / or location according to at least one illustrated embodiment, and in particular detail of an implementation of RF demodulation.

[0037] FIG. 6A and FIG. 6B illustrates a method of processing received ultrasound energy to identify a response from a marker and to provide a visual and / or audible indication of the marker's presence and / or location according to at least one illustrated embodiment, and in particular detail of an implementation of sigma mapping.

[0038] FIG. 7A-FIG. 7D illustrates a method of processing received ultrasound energy to identify a response from a marker and to provide a visual and / or audible indication of the marker's presence and / or location according to at least one illustrated embodiment, and in particular detail of an implementation of target detection. DETAILED DESCRIPTION

[0039] In the following description, specific details are set forth to provide a thorough understanding of various disclosed embodiments. However, one skilled in the relevant art will recognize that embodiments can be practiced without one or more of the specific details, or with other methods, components, materials, etc. In other instances, well-known structures, materials, or operations have not been shown or described in detail in order to avoid

[0040] The word "comprise" and variations of the word, such as "comprising", "comprises" and "comprised", when used in this description and in the claims, are to be interpreted as a non- limiting term. That is, these terms are to be interpreted in the inclusive sense, such that they include not only the recited feature, but also equivalents thereof.

[0041] References throughout this specification to "one embodiment" or "an embodiment" mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. The appearances of the phrase "in one embodiment" or "in an embodiment" in various places in the specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics can be combined in any suitable manner in one or more embodiments.

[0042] 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. It should also be noted that the term "or" is generally employed in its sense including "and / or" unless the content clearly dictates otherwise.

[0043] As used in this specification and the appended claims, the terms left, right, up, and down are used to indicate four directions along two perpendicular axes for a position, location, or cell in a two-dimensional data layout array. For example, the terms left and right can refer to the nearest neighbors in a row on either side of a specified position, location, or cell in an array. Likewise, the terms up direction and down direction can refer to the nearest neighbors in a column that are spaced apart above and below the specified position, location, or cell in the array. Notably, the terms left, right, up, and down are used for convenience and are in a relative sense, not an absolute sense. Thus, the orientation of an array or data layout can be changed, such as rotated 90 degrees, 180 degrees, or mirrored.

[0044] The titles and abstracts provided with the disclosure presented herein are for convenience only and do not interpret the scope or meaning of the embodiments.

[0045] In particular, the systems and methods described herein can use ultrasound to determine the presence or absence and / or location of tissue markers in body tissue. This can be used, for example, to more precisely define the margins of an abnormal or suspicious tissue (e.g., a tumor) in body tissue.

[0046] FIG. 1AA marker 100 to mark body tissue and a distal portion of an instrument 101 selectively operable to implant the marker 100 or a portion thereof into a desired location in the body tissue is shown in accordance with one illustrated embodiment.

[0047] The distal portion of the instrument 101 is shown in cross-section to better illustrate the marker 100. The instrument 101 can take the form of an applicator and the distal portion of the instrument 101 can take the form of a needle or similar structure having a lumen 101a in which the marker 100 is loaded and / or passes through in use. The marker 100 is shown offset (e.g., radially inward) from an inner wall 101b defining the lumen 101a to better illustrate the outer perimeter of the marker 100, although typically the marker 100 will be closely received by, and even in contact with, 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.

[0048] In FIG. 1A In the illustrated embodiment, the marker 100 includes a persistent (e.g., long-term) portion 100a and two additional fast-dissolving portions 100b, 100c. In some embodiments, one or both of the two additional fast-dissolving portions 100b, 100c can be optional and thus omitted in certain embodiments.

[0049] The persistent portion 100a includes a gel body 104a, a plurality of ultrasound-reflective elements 102a, 102b (only two are labeled) that are detectable using ultrasound (e.g., detectable using color Doppler ultrasound), and one or more detectable objects 106 that are detectable using another imaging modality other than ultrasound. The ultrasound-reflective elements 102a, 102b can for example take the form of porous or mesoporous empty shells (as shown in FIG. 1A and / or porous or mesoporous particles (as shown in FIG. 1B as described in greater detail herein. In at least some embodiments, the porous or mesoporous particles are distinguished from the porous or mesoporous shells in that the porous or mesoporous particles do not include a single main lumen to which two, more, or typically all of the pores are connected (except for a sealing coating (hydrophobic coating) that provides a fluid communication path between the outside of the shell and the single main lumen or its interior), as distinguished from a shell that includes at least one main lumen to which two, more, or all of the pores are in fluid communication. As described in greater detail herein, the detectable objects 106 take the form of, for example, clips, wires, or coils (e.g., metal) that are detectable using X-ray imaging.

[0050] For example, the gel body 104a can take the form of a hydrogel that, when implanted in body tissue, partially or fully crosslinks to extend the lifetime, allowing detection by ultrasound and other imaging modalities throughout the diagnostic and treatment process. The gel body 104a that has been partially or fully crosslinked can also advantageously facilitate bioadhesion of the marker 100 to the body tissue implanted by the wound healing process. For example, the gel body 104a provides a fibrotic scaffold that facilitates bioadhesion without glue or adhesive. For example, the polymer combination of the gel body 104a is designed to facilitate a light invasion of natural fibrotic healing.

[0051] A first fast dissolving portion 100b (proximal interior relative to the persistent portion 100a) of the other two fast dissolving portions 100b, 100c likewise can include a gel body 104b and a plurality of ultrasound reflective elements 102c (only one labeled). The gel body 104b of the first fast dissolving portion 100b can be polyethylene glycol (PEG) and is generally uncrosslinked or not highly crosslinked, allowing for rapid hydration and thus rapid activation of its ultrasound reflective elements 102c. This rapidly provides a response to ultrasound, aiding the clinician during the initial implantation of the marker 100. The first fast dissolving portion 100b dissolves after serving the purpose of providing ultrasound response (e.g., backscatter) during implantation.

[0052] A second fast dissolving portion 100c (outermost portion) of the other two fast dissolving portions 100b, 100c includes a gel body 104c and generally omits ultrasound reflective elements. The gel body 104c of the second fast dissolving portion 100c extends slightly beyond the opening 101c of the lumen 101a distal end of the instrument 101. The portion of the gel body 104c of the second fast dissolving portion 100c that extends slightly beyond the opening 101c has a bulbous end 104d to retain the remainder of the marker 100 in the lumen 101a. The gel body 104c of the second fast dissolving portion 100c can consist of or include PEG and is generally uncrosslinked or not highly crosslinked, allowing for rapid hydration and rapid dissolution after serving the function of retaining the marker 100 in the lumen 101a of the instrument 101.

[0053] As shown in the magnified portion, each ultrasound reflective element 102a, 102b, 102c has one or more pores 108 (e.g., mesopores) and contains a fluid 110 (e.g., air or other gas). Each ultrasound reflective element 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 102b to prevent liquid (e.g., water) from entering when implanted in body tissue. The hydrophobic coating 112 may, for example, consist of or include silicone.

[0054] The ultrasound-reflecting elements 102a, 102b, 102c can comprise or consist of silica. When implemented as porous shells, the ultrasound-reflecting elements 102a, 102b, 102c can be formed, for example, by deposition on a template and subsequent removal of the template (e.g., by calcination). One example process of forming ultrasound-reflecting elements 102a, 102b, 102c as porous empty shells begins with polystyrene templates in solution. TMOS and DETA are added to coat the templates with silica. The polystyrene templates are then removed by calcination, and the resulting porous empty shells are then washed and coated with silane. The resulting porous empty shells are then dried. A portion or all of the resulting porous empty shells are then tested to ensure that they are reactive to ultrasound waves. The resulting porous empty shells are then added to the hydrogel to construct the marker 100. For example, the ultrasound-reflecting elements 102a, 102b, 102c can have an overall size or dimension of about 2 mμ and a wall thickness of about 30 nm.

[0055] The ultrasound-reflecting elements 102a, 102b, 102c can alternatively comprise titanium dioxide (TiO2) having the same or similar overall structure (e.g., pores, cavities, surface roughness, dimensions including overall size or dimension (e.g., 2 mμ), shape, wall thickness (e.g., 30 nm)), although they tend to be more toxic and can require separate FDA approval. Other materials having the same overall structure can be viable candidates for the ultrasound-reflecting elements 102a, 102b, 102c, particularly inert materials that remain in the body for a relatively long period of time (e.g., 9 months, 18 months) without generating adverse effects and are compatible with long-term in vivo use, without requiring separate FDA approval.

[0056] In general, the ultrasound-reflecting elements 102a, 102b, 102c will tend to aggregate or cluster in the gel bodies 104a, 104b, for example, as shown and discussed below with reference to FIG. 1B

[0057] ​The cross-linked gel 104a of the persistent portion 100a allows for implantation and retention in the precise location of the target tissue. The plurality of ultrasound-reflective elements 102a, 102b provide a unique response to ultrasound. The clip or wire or coil (e.g., metal) 106 is detectable by X-ray imaging or potentially some other imaging modality. The shape of the clip or wire or coil (e.g., metal) 106 can vary from the persistent portion 100a of the marker 100 to the persistent portion 100a, allowing for easy discrimination of two or more different persistent portions 100a. As described above, the hydrophobic coating 112 seals the fluid 110 in the pores 108 of the ultrasound-reflective elements 102a, 102b, 102c. The hydrophobic coating of the ultrasound-reflective elements 102a, 102b of the persistent portion 100a of the marker 100 is selected to seal the pores 108 for a long period (e.g., 9 months, 18 months) when implanted in body tissue and thus hydrated by bodily fluids. The relatively inner first fast-dissolve portion (with porous shell) 100b facilitates implantation, as the cross-linked gel 104a of the persistent portion 100a does not quickly hydrate during the implantation process and is not visible by ultrasound waves. The relatively outermost fast-dissolve portion (without porous shell) 100b acts as a plug.

[0058] The ultrasound-reflecting elements 102a, 102b of the persistent portion 100a of the marker 100 are the primary source of ultrasound response. The ultrasound-reflecting elements 102a, 102b provide a substantially scattering surface, the porosity of which enhances reflection, fluid 110 being sealed in the pores 108 by the hydrophobic coating 112. The surface roughness and wall thickness of the ultrasound-reflecting elements 102a, 102b, 102c affect the response to ultrasound (e.g., backscatter). The shell structure and its mesoporous nature are controlled by chemical properties and processes, for example by depositing silica spots on a template and subsequently calcining to remove the template and form cavities in the ultrasound-reflecting elements 102a, 102b, 102c. The mesoporous nature allows acoustic energy to enter one or more cavities of the ultrasound-reflecting elements 102a, 102b, 102c, for example into a bubble trapped in the one or more cavities, thereby exciting or enhancing a type of scattering that contributes to detection by Doppler ultrasound. The overall size of the ultrasound-reflecting elements 102a, 102b, 102c and / or the overall size of the aggregates of ultrasound-reflecting elements 102a, 102b, 102c can vary the performance profile. The hydrophobic coating 112 seals the pores 108, preventing fluid from entering the ultrasound-reflecting elements 102a, 102b, 102c, so that the ultrasound-reflecting elements 102b, 102c do not become “wetted,” which would otherwise reduce the signal-to-noise ratio (SNR) of the ultrasound response. The ultrasound-reflecting elements 102a, 102b, 102c generate a B-mode response in ultrasound imaging, which is a composite effect because the color mode is a superposition of the B-mode. The B-mode signal emits a set of B-mode imaging data, which is then interpreted as a color Doppler image using color Doppler techniques. This structure, particularly when suspended in a gel matrix that allows motion in response to ultrasound energy, advantageously provides a broad harmonic that is detectable by color Doppler ultrasound. The number of ultrasound-reflecting elements 102a, 102b, 102c that can be detected is very small.

[0059] An example process of forming the marker 100 includes heating a gel (e.g., a hydrogel composition). The ultrasound-reflective elements can be coated with a hydrophobic polymer. The coated ultrasound-reflective elements are added to a hot mixture of the gel, for example, using a syringe mixer, to, for example, achieve a colloidal dispersion or suspension of the coated ultrasound-reflective elements in the gel. Tubes of gel with ultrasound-reflective elements are manufactured, for example, using a custom syringe, for the durable portion 100a of the marker 100 and the first fast-dissolving portion 100b of the marker 100. Tubes without ultrasound-reflective elements are manufactured, for example, using a custom syringe for the second fast-dissolving portion 100c. The tubes can then be cut to the desired size, for example, based on the respective portions 100a, 100b, 100c of the marker 100. The detectable objects 106 (e.g., clips or wires or coils or metal) can be added to the tubes that will be used for the durable portion 100a of the marker 100, for example, by a mandrel. The tubes are removed from the mandrel and dried.

[0060] FIG. 1B An example marker 120 that marks body tissue is shown, which can be detected by the systems and methods described herein. The various implementations and embodiments are not limited to use with the example marker 120, but can be advantageously used with other markers that include ultrasound-detectable elements. For example, the marker 120 can be the durable portion 100a of the marker 100 FIG. 1A ) or take the form thereof.

[0061] The marker 120 includes a gel body 124a, a plurality of ultrasound-reflective elements 102a (only two are labeled 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 another imaging modality other than ultrasound. The ultrasound-reflective elements 102a can, for example, take the form of porous or mesoporous empty shells (as shown in FIG. 1A ) and / or porous or mesoporous particles (as shown in FIG. 1B ), as described in more detail herein. The detectable objects 106a can, for example, take the form of clips, wires, or coils (e.g., metal) that are detectable using X-ray imaging, as described in more detail herein.

[0062] As shown, the ultrasound-reflective elements 102 can tend to cluster or form clusters or clumps 122. The gel body 124 binds the clusters or clumps 122 of the plurality of ultrasound-reflective elements 102 together. The clusters or clumps 122 can be dispersed throughout the gel body 124, for example, in the form of a colloidal dispersion. When the gel body 124 is hydrated, the clusters or clumps 122 of the plurality of ultrasound-reflective elements 102 are suspended or in a state of suspension and can move relative to one another and / or relative to an external frame of reference over at least a distance and in one or more directions, which can advantageously induce or increase scattering of ultrasound backscatter.

[0063] The gel body 124 can take various forms. The gel body 124 can include one or more hydrogels, for example. The gel body 124 can include a natural hydrogel, such as gelatin. The gel body 124 can include an artificial hydrogel, such as a polyvinyl alcohol (PVA) hydrogel or a polyethylene glycol (PEG) hydrogel. The gel body 124 can include a combination of a natural hydrogel (e.g., gelatin) and an artificial hydrogel (e.g., a PVA hydrogel, a PEG hydrogel). In at least some implementations, the gel body 124 is an at least partially cross-linked hydrogel. In at least some implementations, the gel body 124 is gelatin (e.g., cross-linked gelatin). In at least some implementations, the gel body 124 is a PVA hydrogel (e.g., cross-linked PVA hydrogel). In at least some implementations, the gel body 124 is a PEG hydrogel (e.g., cross-linked PEG hydrogel). In at least some implementations, the gel body 124 includes a combination of a natural hydrogel and an artificial hydrogel (e.g., as respective gel bodies coupled to one another).

[0064] The gel body 124 can be non-absorbable by the body (e.g., for 60 years or more) or can be absorbable by the body over a period of time. In the case of absorbability, the gel body 124 can be designed (e.g., by degree or strength of cross-linking) to last for a period of time in the body, such as for hours, days, a week or weeks, a month or months, or even a year or years. In at least some implementations, an outer or exposed portion of an absorbable gel body 124 can be absorbed faster than more inner portions of the gel body 124 at the time of implantation, such absorption occurring as portions of the gel body 124 are exposed to body tissue (including bodily fluids). In at least some implementations, the gel body 124 can be designed (e.g., controlled cross-linking distribution) to cause some portions to be absorbed faster than others and / or to ensure that some portions last longer than others. Thus, various absorption profiles can be formed on or through the gel body 124.

[0065] Each ultrasound-reflective element is highly reflective to ultrasound. Each ultrasound-reflective element preferably has an irregular surface, for example having a rough outer surface to cause scattering or dispersion of ultrasound energy. The ultrasound-reflective elements 102 can be in the nanometer size range (e.g., 1.8 microns to about 2.2 microns).

[0066] The ultrasound-reflective elements 102 are generally echogenic, and can take any of a variety of forms.

[0067] The ultrasound-reflective elements 102 can be porous or mesoporous, having pores and / or cavities to hold gas. As discussed with reference to FIG. 1A and FIG. 1B The ultrasound-reflective elements 102 can include hydrophobicity to prevent liquid ingress, causing gas to avoid a significant reduction in functionality due to "wetting."

[0068] In at least one embodiment, each ultrasound-reflective element includes a porous hollow shell, for example a silica porous hollow shell, which can be spherical or non-spherical in shape. In at least one embodiment, each ultrasound-reflective element includes a particle that is not a hollow shell, but which is porous, and which can or can not be a porous non-spherical particle. For example, each ultrasound-reflective element can include a respective particle that includes or consists of silica having pores but no single defined hollow interior cavity. Each particle can include one or more layers (not shown in FIG. 1A and FIG. 1B As described below, one or more layers can include a contrast agent to enhance detection by means other than ultrasound imaging. Alternatively, one or more ultrasound-reflective elements can include or consist of one or more contrast agents.

[0069] The gel body 124 (e.g., a hydrogel carrier) and / or some or all of the ultrasound-reflective elements 102 can optionally carry one or more contrast agents 126. The contrast agent 126 may, for example, include one or more contrast agents that enhance detection by direct visual observation or by means of X-ray or MRI imaging. For example, the contrast agent 126 can include a dye to enhance detection by direct visual observation. The dye can advantageously be a fluorescent dye. For example, the dye can include or consist of methylene blue. For example, the contrast agent 126 can include or consist of a radiopaque material (e.g., gold, platinum, tantalum, bismuth, barium, etc.). For example, the contrast agent 126 can include or consist of an MRI imaging material (e.g., as gadolinium, including compounds such as gadolinium-DTPA, ferrous gluconate, ferrous sulfate, etc.).

[0070] Alternatively, one or more contrast agents 126, such as the contrast agents 126 described above, can be incorporated into or around the gel body 124. Detectable objects 106a (e.g., clips, wires, barbs, or helically wound metal wires or other radiopaque elements) can be incorporated into or around the gel body 124.

[0071] In at least one embodiment, each ultrasound-reflective element 102 comprises a hollow shell. Each hollow shell has at least one outer wall forming a cavity. In at least some embodiments, the hollow shell is a multi-layered hollow shell, such as a shell having an inner layer and an outer layer. Each hollow shell is highly reflective to ultrasound waves. Each hollow shell preferably has an irregular surface, such as a rough outer surface to cause scattering or dispersion of ultrasound energy. The hollow shell can be in the nanometer size range.

[0072] In at least some embodiments, each hollow shell can comprise or consist of silica or titania. Some techniques for forming hollow shells in the nanometer size range are described, for example, in U.S. Patent Application 60 / 955,678; U.S. Patent Application 61 / 034,468; U.S. Patent Application 12 / 673,224 (now U.S. Patent 8,440,229); International Patent Application PCT / US2008 / 072972; U.S. Patent Application 13 / 866,940 (now U.S. Patent 9,220,685); U.S. Patent Application 15 / 722,436; U.S. Patent Application 61 / 707,794; International Patent Application PCT / US2013 / 062436; U.S. Patent Application 15 / 706,446; U.S. Patent Application 62 / 135,653; U.S. Patent Application 15 / 559,764; International Patent Application PCT / US2016 / 23492; U.S. Patent Application 62 / 483,274; U.S. Patent Application 62 / 645,677; U.S. Patent Application 15 / 946,479; and International Patent Application PCT / US2018 / 26291.

[0073] In some embodiments, the hollow shell or porous particle, or one or more layers of the hollow shell or porous particle, can comprise one or more contrast agents, such as the contrast agents described above for enhancing visual, radiological, or MRI detection.

[0074] In at least some embodiments, the cavities and / or pores of the ultrasound-reflecting elements 102 comprise a fluid, i.e., a gas, a liquid, or a combination or mixture of a gas and a liquid, although typically a gas that remains gaseous even when interrogated with ultrasound energy during use. The gas can take the form of one material, while the liquid can take the form of another material different from the material forming the gas. Alternatively, the gas and the liquid can be the same material, just in different phase states. For example, the combination or mixture of a gas and a liquid can take the form of a vapor, whether a vapor in a quiescent state or a vapor when heated to a certain threshold level by ultrasound wave energy. For example, the cavities of at least one of the hollow shells can comprise air. Alternatively, the cavities and / or pores of the ultrasound-reflecting elements 102 can comprise an inert gas (e.g., nitrogen, argon). The cavities and / or pores are preferably free of any perfluorocarbons, e.g., in gaseous and / or liquid form.

[0075] Each of the ultrasound-reflecting elements 102 can be porous or mesoporous. In the case where the ultrasound-reflecting elements 102 comprise a fluid, i.e., a gas, a liquid, or a combination or mixture of a gas and a liquid, the ultrasound-reflecting elements 102 can optionally and preferably comprise a coating, preferably a hydrophobic coating, for sealing the cavities and / or pores, at least temporarily sealing the cavities and / or pores thereof against the ingress of fluid from the body tissue into the pores or cavities of the ultrasound-reflecting elements 102.

[0076] In some embodiments, the gel body 124 can be inflatable, e.g., when implanted in body tissue. In some embodiments, the marker 120 can 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 can have a dimensional expansion ratio of about 1 : 1.5 to 1 : 10 from a dry, unexpanded state to a water-saturated, expanded state. The marker 100 can have a dimensional expansion ratio of about 1 :2 to about 1 :3 from a dry, unexpanded state to a water-saturated, expanded state.

[0077] The present disclosure also generally relates to markers 100, 120 (e.g., tissue markers) having physical properties such that the markers 100, 120 are more readily distinguishable by Doppler ultrasound (e.g., color Doppler ultrasound) when implanted in body tissue. Such markers 100, 120 can comprise a gel body 104, 124 having a plurality of ultrasound-reflecting elements 102a, 102b, 102c (e.g., porous shells, porous particles) held in suspension in the gel body 104 and 124. The ultrasound-reflecting elements 102a, 102b, 102c can be, for example, dispersed throughout the gel body 104, 124, e.g., in the form of a colloidal dispersion or colloidal suspension.

[0078] The gel body 104, 124 can take the form of a hydrogel. The gel body 104 and 124 can be fully or partially cross-linked, so long as the ultrasound-reflective elements 102a, 102b, 102c are free to move (e.g., vibrate or oscillate) in at least one dimension (e.g., along at least one axis, preferably along two or more axes) to an adequate degree or distance when the gel body 104, 124 is hydrated to enhance any scattered returns generated by the ultrasound-reflective elements 102b, 102c in response to ultrasound interrogation of the marker 100, 120.

[0079] The ultrasound-reflective elements 102a, 102b, 102c will typically have an irregular surface that results in scattering (e.g., backscattering) in response to ultrasound interrogation of the marker 100, 120. The ultrasound-reflective elements 102a, 102b, 102c typically contain a fluid (i.e., a gas, a liquid, or a combination of a gas and a liquid) that enhances backscattering in response to ultrasound interrogation of the marker 100, 120. The ultrasound-reflective elements 102a, 102b, 102c typically include a hydrophobic coating (e.g., silicone) that maintains the fluid (e.g., air) in the shell for an extended period of time (e.g., 3 months, 9 months, 18 months) even if the marker 100, 120 is subjected to bodily fluids for an extended period of time. This advantageously prevents the ultrasound-reflective elements 102a, 102b, 102c from reducing or even eliminating detectable scattering due to "wetting." The gel body 104, 124 can be dried or dehydrated or freeze-dried until implanted in the body tissue, and then hydrate over time as fluid (e.g., water) is absorbed from the body tissue. The gel body 104, 124 also provides a framework for bioadhesion through the natural healing process of the body tissue in which the marker 100, 120 is implanted. This can secure the marker 100, 120 in place in the body tissue without the use of glue or adhesive.

[0080] The various these physical structures or physical properties of the markers 100, 120 described provide or enhance the scattering (e.g., backscattering) of ultrasound from the markers 100, 120, particularly the changes in position and / or velocity of the ultrasound-reflective elements 102a, 102b, 102c, whether individually or in aggregates or clusters 122, which generates a broad velocity spectrum, thereby facilitating detection using Doppler ultrasound technology. The physical properties of the ultrasound-reflective elements 102a, 102b, 102c or aggregates or clusters 122 of ultrasound-reflective elements 102a, 102b, 102c can vary from the persistent portion 100a of the marker 100 to different persistent portions 100a and / or from the fast-dissolving portion 100b to different fast-dissolving portions 100b, thereby allowing easy differentiation of two or more different persistent portions 100a and / or allowing easy differentiation of two or more fast-dissolving portions 100b based on unique response signals.

[0081] The response of the markers 100, 120 depends on the vibration of the hydrogel matrix of the ultrasound-reflective elements 102a, 102b, 102c. This vibration is influenced by a number of factors. For example, the vibration is influenced by the PEG cross-linking length, which is limited (4-arm attachment between 50-100 nm). This limits the range of motion of the ultrasound-reflective elements 102a, 102b, 102c in the at least partially cross-linked gel body matrix. Also for example, the motion of the ultrasound-reflective elements 102a, 102b, 102c from the incident transmitted wave is limited by the size range of the ultrasound-reflective elements 102a, 102b, 102c (e.g., about 2 um) and the size range of the aggregates or clusters 122 of ultrasound-reflective elements 102a, 102b, 102c (in the range of about 2 to about 6 porous shells per cluster for an aggregate or cluster overall size of about 12 um). Also for example, the vibration is influenced by the interstitial hydrogel span between the hydrophobic aggregates or clusters 122 of ultrasound-reflective elements 102a, 102b, 102c, i.e., the absence of ultrasound-reflective elements 102a, 102b, 102c, which ranges from about 3 um to about 15 um, inclusive, with a typical distance of about 6 um to about 9 um, inclusive. As another example, the vibration is influenced by the polymer mixture cross-linking density, which can be characterized by, for example, the measured value of water swelling at 15 times the dry mass of the polymer matrix.

[0082] Further, the excitation frequency influences the motion behavior of the ultrasound-reflective elements 102a, 102b, 102c, reaching a maximum at a particular frequency (e.g., MHz). For example, a PEG-PEG-amine hydrogel design with a concentration of 8 mg / ml of ultrasound-reflective elements 102a, 102b, 102c per gel has peak variations at 2.76 MHz, 3.33 MHz, and 4.44 MHz.

[0083] In one example, the agglomerates or clusters 122 of ultrasound reflective elements 102a, 102b, 102c have dimensions from about 10 um to about 30 um and are coated or sealed to prevent liquid ingress. Backscatter perturbed by the ultrasound reflective elements 102a, 102b, 102c generates additional harmonics in the return signal. This can be enhanced by choosing a frequency. Changing the wavelength of the ultrasound interrogation or transmit signal to accommodate the scattering structure (e.g., spanning 500 ultrasound reflective elements 102a, 102b, 102c) advantageously results in a broad velocity spectrum. Cross-linking influences the range of motion of the ultrasound reflective elements 102a, 102b, 102c, as does agglomeration. Cross-linking is typically on the order of Angstroms, while the dimensions of the ultrasound reflective elements 102a, 102b, 102c are typically on the order of microns.

[0084] FIG. 2 A marker 200 implanted in body tissue 202 is shown, in accordance with at least one illustrated implementation, along with an ultrasound system 204 having an ultrasound probe or transducer array 206 positioned to detect the marker 200.

[0085] The ultrasound system 204 includes a transmit portion 208 and a receive portion 210. The transmit portion 208 generates drive signals and drives the ultrasound probe or transducer array 206 to transmit pulses of ultrasound energy (e.g., integrated pulses along each beam or angle from individual ultrasound piezoelectric elements, crystals, or transducers of the ultrasound probe or transducer array 206). The receive portion 210 receives signals representative of ultrasound energy detected by the ultrasound probe or transducer array 206 (e.g., can constitute a return signal or series of return signals returned from ultrasound energy scattering or backscattering from the marker or partial marker) and processes the received signals to identify and / or localize the marker based on a known transmit model (e.g., integrated pulses, pulse repetition frequency) using a receive signal processing chain, examples of which are described herein. The ultrasound system 204 can 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 will alternate between modes (e.g., between capturing B-mode frames (e.g., for imaging an anatomical structure) and capturing color Doppler mode frames (for detecting a response of a marker having echogenic features)).

[0086] The transmit portion 208 has an associated fundamental or base frequency of the ultrasound signals to be transmitted by the ultrasound probe or transducer array 206. This can be in a range of 2 MHz to 20 MHz, inclusive, for example.

[0087] The ultrasound system 204 includes a master clock or oscillator 212 that outputs a timing signal. For example, the timing signal output by the master clock or oscillator 212 can be set or used to set the nominal pulse repetition frequency (PRF), i.e., the frequency at which ultrasound pulses repetite. In at least some embodiments, the nominal pulse repetition frequency can advantageously be a default value, or be automatically set, for example, based on the type of marker used and / or based on the type of ultrasound probe or transducer array 206 being used. Less preferably, the nominal pulse repetition frequency value can be set by the operator, at least within a defined range. In other embodiments, the nominal pulse repetition frequency can be a fixed characteristic of a particular ultrasound system 204 and / or marker 200 and / or ultrasound probe or transducer array 206.

[0088] As described herein, in some embodiments, the transmitting portion 208 of the ultrasound system 204 may optionally introduce variations (e.g., nonlinearities) into the ultrasound energy emitted by the ultrasound probe or transducer array 206, and the receiving portion 210 may use these variations (e.g., nonlinearities) (e.g., return signals or a series of return signals that may constitute ultrasound energy scattering or backscattering returns from a marker or a portion of a marker) in the received ultrasound energy to facilitate marker detection (e.g., matched filtering). For example, in at least some embodiments, the transmitting portion 208 preferably includes a variation circuit (VAR) 214 that introduces one or more variations, preferably nonlinear variations, into the ultrasound emission. Nonlinear variations in the ultrasound emission can take any one or more 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 embodiments of the receiving portion 210 and the associated receive signal processing chain can operate successfully without introducing variations or nonlinearities into the output ultrasound emission. It should also be noted that various implementations of the receiving section 210 and the associated receiving signal processing chain can be simplified relative to the implementation shown in at least some cases, where variations, such as nonlinear variations, are introduced into the transmission model, for example allowing the omission or simplification of some filtering, signal or image processing and / or culling additionally included in the shown receiving signal processor chain.

[0089] For example, nonlinear variations in ultrasonic emission can include variations in amplitude or voltage, and thus variations in the output power of the ultrasonic emission. Alternatively or additionally, nonlinear variations can include, for example, variations in the pulse repetition frequency (PRF), which indicates the number of ultrasonic pulses emitted by the ultrasonic probe or transducer array 206 within a specified time period (e.g., typically between 1 kHz and 10 kHz). Alternatively or additionally, nonlinear variations can include, for example, variations in the fundamental frequency of the ultrasonic emission emitted by the ultrasonic probe or transducer array 206. Therefore, optional variations can be variations in any one or more of amplitude or voltage, time, frequency, and / or phase. For example, optional variations can be achieved by adjusting the amplitude using one or more resistors or rheostats, or by one or more delay circuits or capacitors, such as delaying a clock signal. Variations can be periodic, follow a pattern, or be pseudo-random, for example, generated by a pseudo-random number generator (also called a random number generator, RNG). For example, as indicated by the dashed arrows, optional variations can be provided to amplifier 218 to change the amplitude or voltage, or to gate generator 216 to change the PRF or phase, or otherwise to change the fundamental frequency or base frequency of the ultrasonic transmission. These variations can also be provided to receiver 210 to identify which received ultrasonic signals correspond to the response returned by the marker.

[0090] The receiving section 210 receives signals, such as raw RF, representing ultrasonic energy detected by the ultrasound probe or transducer array 206 (e.g., a return signal or a series of return signals, which may constitute a scattered or backscattered return of ultrasonic energy from a marker or part of a marker). The signals typically represent ultrasonic energy reflected or otherwise returned from an object in the field of view of the ultrasound probe or transducer array 206. These objects may include the marker itself as well as body tissue. The signals representing the ultrasonic energy detected by the ultrasound probe or transducer array 206 may also represent outgoing ultrasonic emissions (i.e., ultrasonic pulses emitted from the ultrasound probe or transducer array 206 toward body tissue) and other noise. The receiving section 210 includes a complex receive signal processing chain 220 that includes various receive signal processing stages to remove noise, improve the signal-to-noise ratio, and identify, recognize, and / or locate or position those signals representing ultrasonic energy returned from the marker. For ease of discussion, the signals representing the ultrasonic energy detected by the ultrasound probe or transducer array 206 are sometimes referred to herein as received signals. Although the emitted ultrasound is typically broadband, systems and methods can advantageously employ narrowband detection or reception of ultrasound, for example, detecting or receiving ultrasound in two narrow bands (e.g., about 1.5 times and 2 times the fundamental frequency of the emitted ultrasound), where the harmonics of the response from the marker are prominent relative to the background. As described herein, frame-to-frame analysis can be performed to identify relatively large movements of the echoing material by means of artifacts representing the harmonics.

[0091] The receiving section 210 may include one or more amplifiers 222 to amplify the received signal (e.g., a return signal or a series of return signals, which may constitute a scattering or backscattering return of ultrasonic energy from a marker or a portion of a marker) detected by the ultrasonic probe or transducer array 206. Any or various amplifiers suitable for amplifying signals from the ultrasonic probe or transducer array 206 may be employed.

[0092] The received signal processing chain 220 may optionally include a DC canceller 224, which cancels the DC component from the received signal detected by the ultrasonic probe or transducer array 206.

[0093] The receiving 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, allowing detected reflected or returned ultrasonic pulses that match the pattern of the output ultrasonic pulses to pass through, and filtering out noise and other signals.

[0094] The receive signal processing chain 220 includes a set of RF stages 228. The RF stages 228 process the beamforming RF data, such as applying RF filters and mixing. See below for further details. FIG. 4A more detailed description of RF phase 228 is provided (see RF phase 416).

[0095] The received signal processing chain 220 includes a set of detector stages 230. Detector stages 230 demodulate the raw RF data. See below for details. FIG. 4 Detector phase 230 is described in more detail (see detector phase 418).

[0096] The received 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 ultrasonic signals detected by the ultrasonic probe or transducer array 206. FIG. 2 (See below for reference) FIG. 4 The target phase 232 is described in more detail (see target detection phase 424).

[0097] The receiving section 210 may include one or more presentation stages 234. Presentation stages 234 process data, such as data representing the location or centroid of a marker, and optionally data representing anatomical structures, to allow presentation to a user, for example, via a display screen or other visual and optional auditory cues. For example, a representation of the location or centroid of a marker may be visually represented on a display screen as an overlay or superimposition on a low-resolution representation of the anatomical structure (e.g., captured during B-mode operation) to facilitate visualization of the marker's position relative to various anatomical features of the body. In at least some cases, the centroid of the marker may correspond to the location of a flash or flare effect in color ultrasound imaging. (See below for reference.) FIG. 4 The presentation stage 234 is described in more detail (see scan converter 430 and associated beam geometry 431 and associated B-map data 432, image filtering stage 434, scan converter 436, image filtering stage 440, image merging 442 and image pane 444).

[0098] FIG. 3 An exemplary structure of an ultrasound system 300 according to at least one of the illustrated embodiments is shown. For example, the ultrasound system 300 may be an ultrasound system 204 ( FIG. 2 The implementation method of ).

[0099] The ultrasound system 300 may include a housing or console housing electronic components, such as a three-component circuit card, a single-board computer, and a custom power supply sub-component. The ultrasound system 300 preferably includes all executable instructions (e.g., software, firmware) that execute internally on suitable hardware (e.g., a processor) and provides user output to an LCD screen and speakers within the components of the ultrasound system 300 (preferably housed in the housing or console). During 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 an AC power source (e.g., a power outlet).

[0100] The ultrasonic probe or transducer array 206 is preferably a self-contained transducer assembly (e.g., a linear or two-dimensional array comprising piezoelectric elements, crystals, or transducers). The ultrasonic probe or transducer array 206 is attached to the back of the housing of the ultrasonic system 300. For example, the ultrasonic probe or transducer array 206 can be removed and replaced if defective. The ultrasonic probe or transducer array 206 is managed by and specifically matched to the ultrasonic system 300. In at least some embodiments, the ultrasonic probe or transducer array 206 may, for example, be in the form of a passive ultrasonic probe. In at least some embodiments, the ultrasonic probe or transducer array 206 may, for example, provide identification capabilities. Preferably, user interaction with the ultrasonic system 300 is minimized, for example, by turning on the ultrasonic system 300, placing the ultrasonic probe or transducer array 206 on or relative to a part of the body until a response is received, and prompting the user to set any values ​​or operating parameters.

[0101] The ultrasound system 300 may include, for example, a computer, preferably a single-board computer (SBC) 302, and may also include an ultrasound motherboard 304 communicatively coupled to the SBC 302 via a hardware interface 306 and any associated drivers (e.g., software or firmware communication drivers).

[0102] For example, the ultrasound system 300 may additionally include one or more cards or plates. FIG. 3 (Not shown in the diagram), for example, for managing and distributing power and / or communication (e.g., referred to herein as a carrier card). For example, a carrier card can connect to and power all components of the ultrasound system 300, such as: system power supply, SBC 302, ultrasound motherboard 304, display monitor, USB connector, audio speaker, fan, thermistor, and power switch. The carrier card may also have circuit components such as: tracking transmission regulator, magnetic high-voltage power supply (magnetic), audio amplifier, and / or fan motor controller.

[0103] SBC 302 may have one or more processors and one or more memories or other non-transitory storage media communicatively coupled to one or more processors. For example, processors may include one or more of the following: 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 (PLCs). For example, memories may include one or more of the following: read-only memory (ROM), random access memory (RAM), EEPROM, flash memory, and / or registers. For example, other non-transitory storage media may include one or more of the following: disks and associated disk drives, optical disks and associated optical disk drives, and / or solid-state drives (SSDs). In the illustrated embodiment, single-board computer 302 is shown as including a CPU 308 (e.g., a microprocessor's CPU) and a GPU 310 communicatively coupled to the CPU 308. Those skilled in the art will understand that other sets of components and arrangements of these components are also possible, and the illustrated embodiments are not intended to be limiting.

[0104] The SBC 302 controls the overall operation of the ultrasound system 300 and communicates through many different types of interfaces, such as: front panel interface, front audio interface, USB 2.0 and 3.0 interfaces, PCIe interface, and power input interface. The carrier card routes these signals to its corresponding target connector. Using a separate card or board (e.g., a carrier card) facilitates modifications to the ultrasound system 300, for example, allowing future changes to the SBC 302 to use different hardware and / or operating systems.

[0105] The SBC 302 can be powered by a system +12V power supply distributed via the carrier card. The SBC 302 also shares a common ground with the ultrasound system 300. For example, the connector can be a 2-pin Samtec IPL type connector that supports the maximum inrush current and steady-state current defined from the SBC 302.

[0106] The front panel connector connects the system power-on switch to the SBC 302 via a PSWIN connection and GND. The PWSIN signal is a low-level active signal that signals the SBC 302 to power on or off. This signal is preferably momentarily shorted to ground to activate the power-on or power-off sequence, thus enabling the power switch to function as a momentarily on single-pole switch. Two LED signals may also be provided to indicate the system power status (SUS) and hard disk activity (HD). These signals may be low-level active signals and are operated via a P3v3 SBC power pin. Two LEDs and two resistors, one for each signal, are used to properly visually indicate the status of these two signals. A GND pin may also be provided for power and signal return current, which will be connected to a common system ground and a +3.3V power supply used to power the LEDs as described above. The front audio connector is used to connect to the audio amplifier on the carrier card. The audio connection may be pseudo-differential, thus routing to the audio amplifier input via a suitable audio ground.

[0107] The power distribution network can consist of switches and linear regulators, where the switches can be synchronized with the system image clock. For example, a P5v2 SMPS and a P5V0 regulator can be used to power circuitry on the carrier card. The SMPS output voltage can be set via the voltage drop across 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 clamping circuitry, disabling or enabling the HVP and HVM power supplies. Similarly, for example, an M5v6 SMPS and an M5V0 regulator can be used to power circuitry on the carrier card. The SMPS output voltage can be set via the voltage drop across the M5v0 linear regulator.

[0108] The transmit clamp and enable circuitry is used to place the transmit power supply into a safe state during the sequential shutdown or startup of the system power supply. This circuitry employs appropriate timing between the two signals to ensure sufficient dead time. The FPGA preferably implements an interrupt before switching topologies. To implement the correct power-on and power-off sequence for the HVP and HVM power supplies, an active clamp circuit with an active power enable circuitry can be used. These two signals can be hardware-controlled to implement the timing for implementing a break-before-make switching topology. The HV clamp and HV enable circuitry has two operating states: active clamp and power disabled, and disabled clamp and power enabled. Both states are triggered by the P5v2SMPS power good signal, which is the output of the P5v2 SMPS regulator that actively monitors the voltage on the P12v0 power supply using the SMPS UVLO circuitry. A high level or +12V on the PG signal indicates that the P12v0 voltage is higher than the UVLO. risingThe threshold indicates that the P12v0 power supply is fully on, and the HVP and HVM power supplies can now be safely turned on as well. A low level or 0V on the PG signal indicates that the P12v0 power supply is below UVLO. falling A threshold indicates a fault in the system or a power outage. In either case, the HVP and HVM power supplies are disabled and then clamped to ground.

[0109] The SBC USB 2.0 connector can be used as a ribbon cable connector for interface connection between the SBC 302 and the carrier card. Two sets of HS USB 2.0 signals are used for communication between the SBC 302 and the touch panel or maintenance port. These are standard USB 2.0 interfaces, including VBus, Gnd, and a pair of differential signals.

[0110] The USB 3.0 connector can be a standard USB 3.0 compatible connector. The connection between the SBC 302 and the carrier card is achieved by connecting a standard USB 3.0 interface cable between the two connectors. This is the main communication path for data transmission from the SBC 302 to the ultrasonic motherboard 304.

[0111] The single-board computer 302 implements the operating system 312 that controls the overall operation of the ultrasound system 300, including system startup and system checks, and optionally controls specific operations related to the presentation of outputs (e.g., visual and / or auditory) indicating the location of detected markers.

[0112] The single-board computer 302 executes a detector application 313 for controlling specific detector-related operations of the ultrasound system 300, such as processing the ultrasound probe or transducer array 206 via a receiving signal processing chain as described below. FIG. 2 The detected ultrasonic energy.

[0113] In at least some embodiments, CPU 308 executes a workflow state machine and performs configuration management 314. For example, the workflow or operation of the ultrasound system 300 from startup to processing received signals and data can be specified as various states of the state machine executed by CPU 308. Also, for example, CPU 308 can configure the ultrasound system 300 based on a default set of parameters.

[0114] CPU 308 can also execute logic to handle user feedback management and control 316. For example, CPU 308 can generate a visual representation of the position of a detected marker relative to an anatomical structure and / or a visual representation of the position of an ultrasound probe or transducer. Similarly, for example, CPU 308 can generate an auditory representation of the position of a detected marker relative to an ultrasound probe or transducer, and / or a representation of the direction of motion of the ultrasound probe or sensor relative to the detected marker in one, two, or even three dimensions (e.g., a beep or other sound corresponding to motion away from and / or toward the marker).

[0115] CPU 308 can also execute logic to handle system settings management and control 318. For example, CPU 308 can manage a set of settings for ultrasound system 300, such as using a default set of system settings, or using system settings based on: i) the type of ultrasound probe or transducer that is communicatively coupled to ultrasound system 300, ii) the type of marker used, and / or iii) the type of body tissue (e.g., breast, lung) on ​​which the marker is implanted.

[0116] GPU 310 can implement an ultrasonic processing pipeline 320 to process ultrasonic waves generated by ultrasonic probes or transducer arrays 206. FIG. 2 The retuned ultrasound received will be discussed in more detail in this paper (e.g., see references). FIG. 4 (Receive signal processing chain 402). The GPU 310 can execute logic to implement the detection metric 322 to detect markers from the detected ultrasound, which will be discussed in more detail herein (e.g., see reference 402). FIG. 4 (Receive signal processing chain 402). The GPU 310 can execute logic to implement image synthesis 324 to generate image data that can be presented (e.g., displayed) to the user, which will be discussed in more detail herein (e.g., see references). FIG. 4 (This includes a scan converter 430 and associated beam geometry 431, associated B-mapping data 432, image filter stage 434, scan converter 436, image filter stage 440, image merger 442, and image pane 444).

[0117] The ultrasound motherboard 304 can perform local and ultrasound probe control and is used for various image sequencing events. For example, the ultrasound motherboard 304 may include firmware 323. Although the ultrasound motherboard 304 is shown as a processor 325 in the form of an FPGA, the ultrasound motherboard 304 may more preferably employ one or more GPUs to improve operating speed.

[0118] The ultrasound motherboard 304 may include software and firmware stack (e.g., Cypress USB) 326 to enable communication between the ultrasound motherboard 304 and external devices, which may allow communication with attached ultrasound probes or transducer arrays 206. FIG. 2 This allows for communication and enables programming of the processor 328 (e.g., FPGA or GPU) of the ultrasonic motherboard 304. For example, the ultrasonic motherboard 304 may include one or more communication ports (e.g., two communication ports) providing communication interfaces with external devices. FIG. 3 (Not shown in the image). For example, a port can be in the form of a probe port for connecting to an ultrasonic probe interface and transmitting ultrasonic transmission (TX) and ultrasonic reception (RX) electrical signals to the ultrasonic probe or transducer array 206, respectively. The probe port can have suitable contacts or pins to interface with the ultrasonic probe or transducer array 206 (…). FIG. 2 The complementary structures on the [device] may be used for communication (e.g., electrical) engagement, and / or include physical coupling features or structures. Optional communication ports (referred to as magnetic resonance ports) may be included to provide the synchronous magnetic pulses described elsewhere herein.

[0119] The ultrasound motherboard 304 may include a processor 325 (e.g., an FPGA or GPU), which serves as the central hub for imaging and diagnostic control via an ultrasound probe port and an optional magnetic port. While the processor 325 is shown as an FPGA, in some implementations, one or more GPUs may be advantageously employed.

[0120] For example, the processor 325 of the ultrasound motherboard 304 can implement a scanning state machine 330 to control the ultrasound probe or transducer array 206. FIG. 2 The ultrasound motherboard 304's processor 325 can execute logic to provide front-end chip register access 332. For example, the ultrasound motherboard 304's processor 325 can perform beamforming 334 on received or returned ultrasound signals, activating transducer array elements in a controlled manner during ultrasound energy reception to form a high-quality ultrasound image dataset of the field of interest. Any of a variety of beamforming methods can be employed.

[0121] FIG. 4 An exemplary receiving signal chain 400 of an ultrasound system according to at least one illustrated embodiment is shown. For example, the ultrasound system may be ultrasound system 204. FIG. 2 ) or 300 FIG. 3 The implementation method of ).

[0122] An ultrasound probe or transducer typically has multiple individual piezoelectric elements, crystals, or transducers that emit ultrasound pulses outward, grouped as integrated pulses along multiple beam directions (e.g., integrated pulses from each piezoelectric element, crystal, or transducer along the emission axis of the respective piezoelectric element, crystal, or transducer). The ultrasound probe detects ultrasound energy, and the receiving portion of the ultrasound system performs processing to identify or locate the detected ultrasound energy corresponding to the marker response from all other detected ultrasound energies. This processing should balance the accuracy and speed of the calculations. In particular, the processing speed should be fast enough for use in a surgical environment and sufficient to accommodate the movement of the typically handheld ultrasound probe, which can be moved at different speeds (e.g., velocity and direction) and may even jitter. For example, it is desirable to locate the response from the marker multiple times to improve accuracy. However, this may increase the time required to emit pulses, receive responses, and process the received responses. In at least some embodiments, a marker is considered detected if the response characteristics of the marker are found in three (3) consecutive frames of captured ultrasound data.

[0123] Ultrasonic probe or transducer array 206 ( FIG. 2 The detected ultrasonic energy can be represented by a signal (received signal) and processed by the receive signal processing chain 402 of the receive signal chain 400. The receive signal processing chain 402 can be implemented by circuitry and / or processor-executable instructions stored in non-transitory form on one or more tangible media (e.g., non-volatile memory, rotating storage media (e.g., magnetic hard disk drive, optical disk drive), or solid-state storage media (e.g., solid-state drive (SSD) or flash memory)). The processor-executable instructions can be executed by one or more processors (e.g., microcontroller, microprocessor, central processing unit (CPU), application-specific integrated circuit (ASIC), field-programmable gate array (FPGA), digital signal processor (DSP), and / or graphics processing unit (GPU)). The receive signal processing chain 402 can be executed, for example, via an FPGA, or more preferably by one or more GPUs.

[0124] Specifically, the ultrasonic probe or transducer array 206 ( FIG. 2 Signals can be transmitted via cable 404, communication driver 406 (e.g., USB driver, PCIe driver) and hardware interface 408 (e.g., USB compatible port or connector, PCIe compatible port or header).

[0125] Signals can 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) RF beam data in an arrangement or format desired by the receive signal processing chain 402, for example, by storing signals in a specified format into the frame stream buffer 410. For example, this format or arrangement can be specified in a storage medium (e.g., a non-volatile or read-only memory or EEPROM, referred to as the beam SIM 412). It should be noted that, in addition to the components of the receive signal processing chain 402, the receive signal chain may also include a cable 404, a communication driver 406, a hardware interface 408, the frame stream buffer 410, and / or the beam SIM 412.

[0126] Therefore, the receive signal processing chain 402 can, for example, begin with a full frame of beamformed RF data scheduled from the frame stream buffer 410 by the frame data manager.

[0127] The receive signal processing chain 402 may optionally implement a DC canceller 414 to eliminate the DC component in the beamformed RF data received from the frame stream buffer 410. The DC canceller 414 (also referred to as an integrated canceller) may, for example, apply mean cancellation and depth-based gain to eliminate averages, making differences apparent (e.g., see...). FIG. 5A , FIG. 5B and FIG. 5C (Integrated canceller 506 in the middle).

[0128] The receive signal processing chain 402 may include one or more RF stages 416 to process beamforming RF data, thereby improving the signal-to-noise ratio, for example. RF stages 416 may, for example, implement RF filtering and / or mixing. RF stages 416 may, for example, segment the raw RF data. For example, RF stage 416 may separate or segment raw RF data (pulse-integrated data) representing a response from a marker from raw RF data (e.g., non-pulse-integrated information or B data) representing other types of returns or reflections that may represent reflections from anatomical structures (e.g., 508, FIG. 5A-FIG. 5C For example, RF stage 416 may employ one or more RF filters (e.g., finite impulse response (FIR) bandpass filters) to perform this real-time digital signal processing. RF stage 416 may, for example, process multiple RF data streams, such as two pulse-integrated RF data streams and a B RF data stream. For example, RF stage 416 may include multiple mixers (e.g., 510a, 510b, 510c, ...). FIG. 5A-FIG. 5C These mixers generate in-phase or quadrature (IQ) RF signals for various pulse-integrated and non-pulse-integrated RF data streams. For example, mixers (e.g., 510a, 510b, ...) FIG. 5A-FIG. 5CThe two pulsed integrated data streams can be mixed with corresponding multiples (e.g., 1.5 times and 2 times the fundamental frequency) of the emitted ultrasound. RF mixing can result in two or more different multiples of the ultrasound fundamental frequency. It should be noted that using 1.5 times the fundamental frequency yields better results than using only 2 times the fundamental frequency, as this can address potential “blinding effects” by eliminating the ultrasound probe from detecting the emitted ultrasound signal rather than the returned signal. RF stage 416 can also employ one or more low-pass filters, such as those to remove negative frequencies from the IQ signal (e.g., see 512a, 512b, 512c). FIG. 5A-FIG. 5C The RF stage 416 may also employ one or more notch filters, for example, to filter out the fundamental frequency of ultrasound.

[0129] The receive signal processing chain 402 may include one or more detector stages 418. Detector stages 418 may demodulate the separated raw RF data. Demodulation is commonly referred to as detection, which removes the carrier signal and reconstructs the signal envelope of each RF data stream (e.g., envelope detection) (e.g., 514a, 514b, 514c). FIG. 5A-FIG. 5C Therefore, detector stage 418 can, for example, remove the transducer pulse frequency from the data to prevent or reduce ripple. For example, envelope detection can demodulate the RF signal or convert it back to an amplitude representation.

[0130] Various methods can be used to perform demodulation or envelope detection, such as: i) implementing quadrature (IQ) detection, or ii) applying the Hilbert transform. Quadrature (IQ) detection mixes (essentially multiplies) in-phase and quadrature-phase sine waves with the input signal, emphasizing the signal content at that frequency and reducing all other content. This can be implemented in hardware or software. The original signal after IQ detection may still include ripple (e.g., at twice the carrier frequency), which can be advantageously addressed by low-pass filtering. Applying the Hilbert transform shifts the ripple peaks in the RF data by half in time towards the troughs. The resulting modified signal can be combined with the original signal, such that one signal fills the ripple of another, thereby estimating the envelope amplitude. The result is a good approximation of the pulse energy, reducing ripple while maximizing detail.

[0131] The receive signal processing chain 402 may optionally perform logarithmic compression (i.e., logarithmic compression) 420 on the output from the RF stage 416.

[0132] The receive signal processing chain 402 may optionally perform logarithmic compression (i.e., logarithmic compression) 422 on the output from the detector stage 418.

[0133] The receive signal processing chain 402 may include one or more target stages 424 to perform spatial or “image” processing on data representing ultrasound signals detected by the ultrasound probe or transducer array 206. FIG. 2 The target phase 424 may, for example, perform frame-to-frame comparisons, referred to herein as σ-mapping, to identify, for example, variations or differences in the received ultrasound data between frames (e.g., 518, FIG. 5A-FIG. 5C σ-mapping can maximize the signal-to-noise ratio, for example, by extracting the target's response (e.g., the return signal from the marker) from the received signal data. The target phase 424 may also include target detection (e.g., 520, FIG. 5A-FIG. 5C For example, a target best-fit algorithm can be used. The target best-fit algorithm separates the spots that best match the target spatial criteria (e.g., the ultrasonic response shape of the marker).

[0134] The receive signal processing chain 402 may include one or more focus mixers 426 (also referred to as focus combiners). The focus mixer 426 acquires data from multiple focal depths in previous stages and flattens the data. For example, the focus mixer 426 may acquire data from, for example, two focal depths (e.g., 48 x 2640 x 2 data) and generate a smaller dataset (e.g., 48 x 2640 data). The focus mixer 426 may combine B-focus beams and allow the detector to pass through the B-flow (e.g., 530, FIG. 5A-FIG. 5C ).

[0135] The receive signal processing chain 402 can perform one or more decimations 428 to reduce the size of the dataset. For example, the receive signal processing chain 402 can perform detector decimations (e.g., detector decimation 522) on samples in the beam. FIG. 5A-FIG. 5C ) and B-sample extraction (e.g., B-sample extraction of 528, FIG. 5A-FIG. 5C ).

[0136] The receive signal processing chain 402 may include one or more scan converters 430, 436 and associated beam geometry 431, as well as associated B-mode mapping data 432 and associated color mapping data 438. Scan converters 430, 436 output scan conversions (e.g., see D-mode scan conversion 524) to the B-mode image data and color mode image data. FIG. 5A-FIG. 5C B-scan conversion 532, FIG. 5A-FIG. 5C ).

[0137] The receive signal processing chain 402 may include one or more image filter stages 434, 440 for filtering various components of an image or image data (e.g., B-mode image data; color mode image data).

[0138] The receive signal processing chain 402 may include one or more image mergers 442 operable for merging image data (e.g., B-mode image data and color mode image data).

[0139] The receiving signal processing chain 402 may include one or more image panes 444 for presenting merged image data.

[0140] The receiving signal chain 400 of the ultrasound system may include, for example, a system interface (Vdevice model) 446 for reading registers and tables.

[0141] The receiving signal chain 400 of the ultrasound system may include a graphics interface (pipeline device VM view model) 448, which interfaces, for example, between a graphics engine (C++ CLR interface) 450 and a rendering framework (e.g., WPF for Windows applications) 452 to render images via a display and / or a driver (view) 454, such as via a markup language layer (XAML UIDEF) 456. The pipeline device VM view model 448 reads and writes external files (e.g., configuration or rendering files 458) and external libraries (e.g., scripts 460).

[0142] FIG. 2 A method 500 is illustrated, according to at least one illustrated embodiment, for processing received ultrasonic energy to identify a response from a marker and provide a visual and / or auditory indication of the marker's presence and / or location, with particular detail on an implementation of RF demodulation. For example, method 500 may be implemented by the receiving portion 210 of an ultrasonic system 204 (… FIG. 2 )accomplish.

[0143] According to at least one of the illustrated embodiments, method 500 can be implemented in hardware, software, and / or firmware. For example, the hardware may include: an analog-to-digital converter (ADC), a processor-based computer system employing one or more processors and memory or other non-transitory storage media, and one or more of the following: a field-programmable gate array (FPGA), a graphics processing unit (GPU), and / or an application-specific integrated circuit (ASIC), which may be implemented, for example, on one or more cards or boards. For example, the processor may include one or more of the following: 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 programmable logic controller (PLC), etc. For example, the memory may include one or more of the following: read-only memory (ROM), random access memory (RAM), EEPROM, flash memory, and / or registers, etc. For example, other non-transitory storage media may include one or more of the following: a hard disk and associated hard disk drives, an optical disk and associated optical disk drives, and / or a solid-state drive (SSD), etc.

[0144] Although not shown, it can be seen from the ultrasonic probe or transducer array 206 ( FIG. 2 The system receives analog transducer signals. The received analog transducer signals have a center frequency (e.g., a center frequency of 2.76 MHz). Optionally, the received analog transducer signals are digitized (e.g., via an analog-to-digital converter (not shown)).

[0145] At position 502, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 The beamforming receives the input frame of the RF data (e.g., raw sample data of the input frame). For example, the receiving section 210 can process the raw sample data of the incoming frame received via an ultrasound probe or transducer.

[0146] At position 504, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 The receiver 210 can map the incident beam to a specified or otherwise defined format. For example, the receiver 210 can map the received ultrasound signal to a frame stream buffer in a specified format.

[0147] At position 506, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 The integrated canceller applies mean cancellation and depth-based gain to beammapped RF data to, for example, remove the average value, making differences more apparent.

[0148] At position 508, the receiving section 210 of the ultrasound system 204 ( FIG. 2The RF splitter performs RF splitting, separating non-integrated beams (e.g., beams without a specified pulse pattern) from integrated beams (i.e., beams with a specified pulse pattern) and generating multiple sets of RF data, such as multiple sets of integrated beam RF data and one set of non-integrated beam RF data. For example, the output may include two sets of integrated beam RF data (referred to as D-beam path 1 and D-beam path 2) and one set of non-integrated beam RF data (referred to as the B-beam). This set of integrated beam RF data will primarily represent the response from a marker (e.g., resonance or beat frequency response), while the set of non-integrated beam RF data may primarily represent the structure (e.g., reflections from an anatomical structure). Although the RF splitter is shown as having three branches providing two sets of integrated beam RF data and one set of non-integrated beam RF data, in other embodiments, the RF splitter can be implemented with a different number of branches. This can advantageously separate the B data from the final defined number (e.g., four) of integrated beams. In some cases, such as when an RF detector filter is enabled, this can be implemented or named RF detector filtering. For example, the receiving section 210 of the ultrasound system 204 ( FIG. 2 FIR bandpass filters can be applied to separate integrated beams (e.g., beams with a specified pulse pattern) from non-integrated beams (beams lacking a specified pulse pattern).

[0149] The output data of the RF splitter is processed by three parts of a signal chain. These three parts consist of sets of operations that are typically performed in parallel on two sets of data, including pulse integrated response data and B data. The operations of these typically parallel sets are represented by a shared three-digit reference number followed by lowercase letters “a”, “b”, and “c”.

[0150] At locations 510a, 510b, and 501c, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 RF mixing is performed using RF mixers (RF mixer D, path 1, RF mixer D, path 2, and RF mixer B) to generate RF direct quadrature (IQ) signals using various mixing frequencies and coefficients. RF mixing (RF mixer D, path 1, RF mixer D, path 2) can generate two or more different multiples of the fundamental frequency or base frequency of the ultrasonic emission (e.g., 1.5 times the fundamental frequency, 2 times the fundamental frequency, e.g., when the fundamental frequency or base frequency is 2.76 MHz). This can advantageously address the potential "blinding effect" of the output ultrasonic energy and / or improve the ability to identify which signals correspond to the marker response.

[0151] At locations 512a, 512c, and 512c, the receiving portion 210 of the ultrasound system 204 ( FIG. 2Optionally, low-pass filtering can be performed using low-pass filters (D low-pass filter 1, D low-pass filter 2, and B low-pass filter 1, respectively). For example, this can remove negative frequencies from the IQ signal.

[0152] At locations 514a, 514b, and 514c, the receiving portion 210 of the ultrasound system 204 ( FIG. 5A-FIG. 5C For example, a low-pass filtered RF IQ signal can be demodulated by performing envelope detection (D envelope detection 1, D envelope detection 2, and B envelope detection, respectively). This can advantageously remove the carrier signal and reconstruct the signal envelope, for example, by converting the IQ signal back to an amplitude representation.

[0153] like FIG. 5A-FIG. 5C As shown, method 500 may also include performing B-log compression on the B data in 516, for example, compressing the data range to a desired range (e.g., 0 to 255).

[0154] like FIG. 6A As shown, method 500 may further include performing a σ-mapping on the D-envelope detection 1 and the results of D-envelope detection 1 at 518. Method 500 may further include performing object detection at 520 using the σ-mapping generated by σ-mapping 518 and the B-log compressed data from B-log compression 516. See references respectively. FIG. 6B , FIG. 7A-FIG. 7D and FIG. 5A-FIG. 5C A more detailed explanation of σ mapping 518 and object detection 520.

[0155] like FIG. 5A-FIG. 5C As shown, method 500 may also include performing detector extraction at 522 to, for example, reduce the sample size in the detector beam.

[0156] like FIG. 5A-FIG. 5C As shown, method 500 may further include providing the processed data to the D-scan converter or performing a D-scan conversion on the data at 524.

[0157] like FIG. 5A-FIG. 5C As shown, method 500 may also include performing B-bilateral filtering at 526, for example, smoothing an R-Theta filter with an NxN kernel.

[0158] like FIG. 5A-FIG. 5C As shown, method 500 may also include performing B-sample extraction at 528, for example, reducing the number of samples in the beam.

[0159] like FIG. 5A-FIG. 5C As shown, method 500 may further include performing focus mixing at 530 to combine the B-focus beams and allow the detector beams to cross into a B-data stream.

[0160] like FIG. 6AAs shown, method 500 may also include performing a scan conversion at 532, for example, outputting a scan conversion suitable for visual presentation.

[0161] FIG. 6B and FIG. 2 A method 600 is illustrated, according to at least one illustrated embodiment, for processing received ultrasonic energy to identify a response from a marker and provide a visual and / or auditory indication of the marker's presence and / or location, with particular detail on an implementation of σ-phase σ-mapping. For example, method 600 may be implemented by the receiving portion 210 of an ultrasonic system 204 (… FIG. 5A-FIG. 5C To achieve this.

[0162] The σ phase divides the RF data into multiple (e.g., two) frequency bands centered at different multiples of the fundamental frequency (e.g., the first band centered at 1.5 times the fundamental frequency, and the second band centered at 2 times the fundamental frequency). A roughly parallel set of operations is applied to the two sets of data, which are processed by the RF demultiplexer 508 (…). FIG. 2 The output of the two branches of the part is obtained by processing.

[0163] At locations 602a and 602b, the receiving portion 210 of the ultrasound system 204 ( FIG. 5A-FIG. 5C Demodulating RF data, for example by performing envelope detection at two different multiples of the fundamental frequency (e.g., 1.5 times and 2 times the fundamental frequency). It is worth noting that envelope detection 602a, 602b (D-envelope detection 1, D-envelope detection 2) precedes... FIG. 6A The values ​​in the middle are shown as envelope detection 514a and 514b, respectively, and in FIG. 6B and FIG. 2 (This is again included, only to provide context for method 600). Therefore, in at least some embodiments, envelope detection 602a, 602b may not be strictly considered as part of σ-mapping method 600, but may be performed as a separate or upstream part of the return signal processing chain that is fed into the σ-mapping part of the return signal processing chain.

[0164] At 604a and 604b, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 The ultrasound system 204 employs or applies integrated focusing hybridization to, for example, blend the emission (tx) focusing patterns of the data generated by envelope detection 602a, 602b. For example, once the envelope is detected, the receiving portion 210 of the ultrasound system 204 ( FIG. 2Alternating focal depths (e.g., a first focal depth and a second focal depth) are mixed at the transition depth. Adding two or more depths together can eliminate some emission noise. In the current implementation, two focal depths are used because including an additional focal depth would significantly increase the time required to emit, detect, and process ultrasound, thus imposing undesirable limitations on hand and ultrasound probe movement. Processing after this stage can be performed laterally at the same depth.

[0165] At locations 606a and 606b, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 A lateral canceller is employed or applied. For example, a lateral canceller subtracts the average of other beams from each integrated sample. For example, a 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).

[0166] At locations 608a and 608b, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 This involves determining or calculating the sum of differences. For example, by calculating the absolute difference at each location within a beam, two beams in a ensemble can be reduced to one beam. This operation is helpful in extracting temporal differences from RF data.

[0167] At locations 610a and 610b, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 This determines or calculates the lateral standard deviation (also known as the cross-beam standard deviation). For example, receiver 210 calculates the standard deviation of the number of beams (e.g., 3 beams) around the target or "current" beam. The window size (e.g., 3) is set by the environment variable VPM_LATERAL_WINDOW. This operation helps to obtain spatial differences in the lateral plane.

[0168] At locations 612a and 612b, the receiving section 210 of the ultrasound system ( FIG. 2 Two streams can be combined in various ways. For example, the data can be squared to highlight the dynamic range of the variable response.

[0169] At position 614, the receiving section 210 of the ultrasound system ( FIG. 2 The received or detected ultrasound data streams can be combined in various ways (e.g., two streams, one at 1.5 times the fundamental frequency and the other at 2 times the fundamental frequency). For example, the 1.5x and 2x data paths can be combined by multiplying each position in the beam.

[0170] At position 616, the receiving section 210 of the ultrasound system ( FIG. 2 Frame cancellation can be optionally employed or applied, such as performing frame-to-frame cancellation and smoothing. Alternatively, frame cancellation can be disabled so that data passes through this operation unaffected.

[0171] At position 618, the receiving section 210 of the ultrasound system ( FIG. 2 Optionally, logarithmic compression (called logarithmic compression) can be applied or performed on the data. Logarithmic compression can advantageously map data to a specified range (e.g., a range of 0-235, where 235 equals 160 dB). In this example, the step size is 681 dB per step.

[0172] At position 620, the receiving section 210 of the ultrasound system ( FIG. 2 It provides σ-mapping outputs (e.g., σ-graphs), which are the outputs of σ-mapping.

[0173] FIG. 2 A method 700 is illustrated, according to at least one illustrated embodiment, for processing received ultrasonic energy to identify a response from a marker and provide visual and / or auditory indication of the marker's presence and / or location, with a particular detailed description of an implementation of target detection in a target detection phase. For example, method 700 may be derived from the receiving portion 210 of an ultrasonic system 204 (…). FIG. 2 )accomplish.

[0174] In general, target detection may include performing 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 flat σ-sector data (e.g., arranged in a 48x2640 matrix) to generate connectivity and distance matrices of equal size. Once the distance matrices are filled, positions within the matrix are set as negative culling codes to indicate the reason for the position's invalidity. At the end of the culling chain, a set of potential blob centroids and their left, right, upper, and lower extents remain. These centroids are then evaluated in a centroid reduction sequence to find the best-fit centroid. This centroid is then passed to a centroid tracking algorithm or process. The use of centroids is particularly advantageous in applications where markers are used to label tissue for examination, monitoring, excision, and / or ablation.

[0175] At position 702, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 It receives one or more σ-maps. (See above for reference.) FIG. 2 and FIG. 2 σ-mapping was discussed.

[0176] At position 704, the receiving portion 210 of the ultrasound system 204 ( FIG. 2This tool can construct, build, or calculate beam histograms (e.g., average, peak, maximum) for the corresponding beams in one or more beams. Beam histograms can be used to inform dynamic threshold / flood sector assessments at the implementation site.

[0177] At position 706, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 This function constructs, modifies, or computes frame histograms (e.g., average, peak, maximum) for corresponding frames in one or more frames. Frame histograms can be used to inform dynamic threshold / flood sector assessments at the implementation level.

[0178] At position 708, the receiving section 210 of the ultrasound system 204 ( FIG. 2 An adaptive threshold is applied to the data. For example, the receiving section 210 can set all values ​​less than the σ threshold to zero (0). The σ threshold can be set by a harmonic σ threshold register. For example, the σ threshold can be 75, equivalent to 51.08 dB. The σ threshold lays the foundation for establishing spatial connectivity. This value can be intentionally set below the expected target minimum to ensure that the measurement includes larger objects that may have sub-regions that meet the target minimum.

[0179] At position 710, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 Focus merging is implemented or applied. Focus merging combines focus sets. For example, focus merging can take a set of data from a previous stage (e.g., 48x2640x2 data) and flatten the data to create a smaller, flattened dataset (e.g., 48x2640 data). By replicating the data of the depth set, this facilitates alternating focus segmentation in at least one implementation. Other implementations may be able to omit this and / or employ other methods.

[0180] At position 712, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 The connection graph is implemented or applied. For example, the receiving part 210 calculates the horizontal and vertical connection information for each cell. The connection graph establishes left, right, top, and bottom connections (i.e., nearest neighbors in rows and columns) for active samples.

[0181] In 714, the receiving section 210 of the ultrasound system 204 ( FIG. 2 The receiving section 210 determines or calculates distances, such as the RUD distance to the edge of each cell spot. For example, the receiving section 210 calculates the left, right, top, and bottom distances from the active sample to the non-connected edge (i.e., the distance in the row and the distance in the column).

[0182] In 716, the receiving section 210 of the ultrasound system 204 ( FIG. 2 ) Determine or calculate the smoothing distance. For example, receiver 210 ( FIG. 2It can average the distance data in the left, right, up, and down directions to smooth out small gaps.

[0183] At position 718, the receiving section 210 of the ultrasound system 204 ( FIG. 2 The receiving unit 210 performs σ-threshold rejection to filter out any out-of-bounds regions. For example, the receiving unit 210 can remove regions based on a σ-threshold. For instance, the receiving unit 210 checks for positions in the distance data where the left, right, top, and bottom distances are zero, and sets rejection codes accordingly. Then, the receiving unit 210 checks for positions in the σ-data where the value is less than the target minimum σ-threshold, and sets rejection codes accordingly. The rejection code can be a Boolean flag or value indicating a binary state of rejection or non-rejection.

[0184] At position 720, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 Region removal is performed. Region removal can be based on the σ content and B content fed from the B processing chain 717 and the B logarithmic compression 719. For example, the receiving section 210 checks for locations in the distance data where the connection width is too wide and sets a removal code accordingly. Similarly, for example, the receiving section 210 checks for locations in the B data where the value exceeds the B threshold and sets a removal code accordingly.

[0185] At position 722, the receiving section 210 of the ultrasound system 204 ( FIG. 2 Orphan removal is performed. Orphan removal can delete blob orphans created in the previous stage. For example, receiving unit 210 searches for locations previously removed due to being too wide within the region of interest (ROI) associated with the current active location, and sets a removal code accordingly when any such location is found. The ROI is defined by the left, right, top, and bottom distances of the active location. Receiving unit 210 searches for smaller ROIs and tracks the number of locations removed due to being below a threshold σ. Smaller ROIs are defined by subranges of the left, right, top, and bottom distances of the current active location. If the ratio of removed locations to valid locations exceeds a threshold, a removal code is set.

[0186] At position 724, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 Improve distance calculation, for example, by recalculating the distance when no rejection value is reached. For example, the receiving part 210 can step out from the active position in the left, right, up, and down directions and count the number of steps in each direction until the rejection value is reached. These counts will be saved as new left, right, up, and down distances for the active position.

[0187] At position 726, the receiving section 210 of the ultrasound system 204 ( FIG. 2The receiving section 210 evaluates and excludes certain regions, such as filtering out out-of-bounds areas. For example, the receiving section 210 can check the width (total left-right distance) and height (total vertical distance) of the active position based on minimum size requirements. For example, the minimum size requirements can be defined by a set of registers, referred to herein as the DT target minimum width and DT target minimum height. If the minimum size requirements are not met, the receiving section 210 sets the exclusion code accordingly.

[0188] At position 728, the receiving section 210 of the ultrasound system 204 ( FIG. 2 The distances can be further refined, for example, by recalculating the distances without rejection values. For instance, the receiving unit 210 can step out from the active position in the left, right, up, and down directions and count the number of steps in each direction until a rejection value is reached. These counts will be saved as new left, right, up, and down distances for the active position.

[0189] At position 730, the receiving section 210 of the ultrasound system 204 ( FIG. 2 The first round of centroid reduction is performed. For example, the receiving part 210 can reduce the distance set as the highest fit within a specified range. For example, the receiving part 210 can calculate the width ratio, height ratio, and area / distance product for each valid centroid. The receiving part 210 can recursively compare these values ​​in pairs until a single best fit is reduced.

[0190] At position 732, the receiving section 210 of the ultrasound system 204 ( FIG. 2 Perform a second round of centroid reduction. For example, the receiving part 210 can again reduce the set to the highest matching within the specified range.

[0191] At position 734, the receiving portion 210 of the ultrasound system 204 ( FIG. 2 The receiving section 210 performs centroid tracking, such as generating a centroid tracking table or other data structures. It can acquire the σ and distance matrix, as well as the best-fit centroid, and track the blob over time (e.g., frame-to-frame). The receiving section 210 can maintain a state machine that updates target tracking attributes across various states, such as two main states: search and tracking. Each main state can have sub-states, such as those controlling responsiveness, persistence, and confidence. The main states and related operations are discussed below.

[0192] At position 736, the receiving section 210 of the ultrasound system 204 ( FIG. 2 Centroid merging can be implemented or applied. It can be used to format and / or route the required data for display. In standard operating mode, centroid merging can route isolated best-fit blobs with target features (e.g., crosshairs, shading), but can also route distance data, culling codes, test patterns, etc. The receiving section 210 can update the centroid tracking table accordingly.

[0193] At position 738, the receiving section 210 of the ultrasound system 204 ( FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 FIG. 2 One or more decimations can be performed to reduce the size of the dataset. For example, the receive signal processing chain 402 can decimate the output data to prepare for scan conversion.

[0194] As mentioned above, there are two main states: search and tracking.

[0195] In the search state, the receiving section 210 attempts to detect the same target multiple times, for example, attempting to detect the same target for three consecutive (3) frames. This can provide a higher confidence level than a single detection. While three (3) frames in a row are provided as an example, more or fewer frames can be used, although it is believed that three (3) frames provide a good balance between speed and accuracy. If the centroid of each subsequent detection is within the target range of the target in the previous frame, it will meet the condition for continuous detection. The continuous detection counter is incremented each time a detection is successful. In response to a specified number (e.g., three (3)) of detections of the same target, the initial tracking properties are set and the state machine is transitioned to the tracking state. The continuous detection counter is reset immediately after a frame in which no target is detected.

[0196] In tracking mode, the receiving part 210 determines whether the target is within the region of interest (ROI) of the target tracking.

[0197] If the target is within the target tracking ROI, then the receiving part 210 updates the tracking attributes, and the state machine's state is maintained as tracking.

[0198] On the other hand, if the target is not within the target tracking ROI, the receiving part 210 executes the following algorithm.

[0199] The receiving section 210 increments a set of continuous counters (called ROI continuous counters; and precise continuous counters).

[0200] The receiving section 210 determines whether the target is a confidence (e.g., level 2) detection. If so, the receiving section 210 updates the tracking attributes of the new target, and the state machine is maintained in the tracking state.

[0201] Then, when the ROI persistence counter is less than or equal to 0, the receiving section 210 enters the outer loop.

[0202] Then, when the precision duration counter is less than or equal to 0, the receiving section 210 enters the inner loop.

[0203] Then, the receiving part 210 clears the tracking attributes of the current target (clears the target_current tracking attribute), and the state machine transitions to the tracking lost state.

[0204] Once the ROI persistence counter is greater than zero (0), the receiving section 210 exits the outer loop. The receiving section 210 clears the tracking attributes and changes the state machine's state to search.

[0205] For example, tracking attributes can include target confidence and target tracking ROI. In centroid tracking, target confidence is determined by summing counters for all locations with high σ (e.g., greater than 125.957 dB) and non-zero σ within the target range. If the ratio of high σ to non-zero σ is greater than a threshold (e.g., 25%), the confidence increases (e.g., from 1 to 2). The target ROI is the full beamwidth of the sector, with top and bottom being the precise top and bottom of the target plus margin.

[0206] The above detailed description illustrates various implementations of the device and / or process using block diagrams, schematic diagrams, and examples. As long as these block diagrams, schematic diagrams, and examples include one or more functions and / or operations, those skilled in the art will understand that each function and / or operation in these block diagrams, flowcharts, or examples can be implemented individually and / or collectively by various hardware, software, firmware, or virtually any combination thereof. In one implementation, the subject matter can be implemented using an application-specific integrated circuit (ASIC). However, those skilled in the art will recognize that the implementations disclosed herein can be implemented, in whole or in part, equivalently in standard integrated circuits, as one or more computer programs running on one or more computers (e.g., programs running on one or more computer systems), as multiple programs running on multiple controllers (e.g., microcontrollers), as running on at least one processor (e.g., microprocessor), as firmware, or as virtually any combination thereof, and that designing circuits and / or writing software and / or firmware code according to this disclosure will be entirely within the skill of those skilled in the art.

[0207] Those skilled in the art will recognize that many of the methods or algorithms described herein may employ additional actions, omit some actions, and / or perform actions in a different order than the specified order.

[0208] Furthermore, those skilled in the art will understand that the mechanisms taught herein can be distributed as program products in various forms, and the illustrative implementations are equally applicable, regardless of the specific type of signal-bearing medium actually used to perform the distribution. Examples of signal-bearing media include, but are not limited to, recordable media such as floppy disks, hard disk drives, CD-ROMs, digital magnetic tapes, and computer memory.

[0209] The various embodiments described above can be combined to provide further embodiments. U.S. Patent Application 60 / 955678; U.S. Patent Application 61 / 034468; U.S. Patent Application 12 / 673224 (now U.S. Patent 8440229); International Patent Application PCT / US2008 / 072972; U.S. Patent Application 13 / 866940 (now U.S. Patent 9220685); U.S. Patent Application 15 / 722436; U.S. Patent Application 61 / 707794; International Patent Application PCT / US2013 / 062436; U.S. Patent Application 15 / 706446; U.S. Patent Application 62 / 13 The entire contents of U.S. Patent Application No. 15 / 559764, U.S. Patent Application No. 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, U.S. Patent Application No. 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 incorporated herein by reference. Where necessary, aspects of the implementation may be modified to provide further implementations employing systems, circuits, and concepts from various patents, applications, and publications.

[0210] Based on the detailed description above, these and other modifications can be made to the embodiments. Generally, the terminology used in the claims should not be construed as limiting the claims to the specific embodiments disclosed in the specification and claims, but should be understood to include all possible embodiments and the full scope of equivalents enjoyed by these claims. Therefore, the claims are not limited to this disclosure.

Claims

1. A method of operating in an ultrasound system having a transmitting portion and a receiving portion for detecting at least the presence of a response from a tissue marker, the method comprising: A set of driving signals is generated by the transmitting part of the ultrasound system; The set of drive signals is provided to an ultrasonic probe having at least one ultrasonic transducer, so that at least one ultrasonic transducer emits ultrasonic energy in the form of an integrated pulse, the corresponding integrated pulse being emitted along the respective beam of each of a plurality of beams and at a plurality of focal depths. as well as A series of return signals, representing the ultrasonic energy detected by the ultrasonic probe, are processed by the return signal processing chain of the receiving section of the ultrasonic system. This processing includes performing target detection, which comprises: Generate a σ-plot indicating the changes between returned signal data frames; and At least in part, a target best-fit process is performed based on the σ-plot to detect the presence of a response signal from the tissue marker.

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

3. The method according to claim 1, wherein, Processing a series of return signals via the return signal processing chain includes mixing the return signals with a first multiple of the fundamental frequency of the ultrasound, and mixing the return signals with a second multiple of the fundamental frequency of the ultrasound, the second multiple being different from the first multiple.

4. The method according to claim 3, wherein, Mixing the returned signal with a first multiple of the fundamental frequency of the ultrasound includes mixing the returned signal with twice the fundamental frequency of the ultrasound, and mixing the returned signal with a second multiple of the fundamental frequency of the ultrasound includes mixing the returned signal with 1.5 times the fundamental frequency of the ultrasound.

5. The method according to any one of claims 2 to 4, wherein, Processing a series of return signals via the return signal processing chain also includes filtering the return signals generated by mixing with the first multiplier and the second multiplier to at least partially filter out the ultrasound emitted by the at least one ultrasonic transducer.

6. The method according to claim 2, wherein, Processing a series of return signals via the return signal processing chain includes performing envelope detection on each signal generated by mixing with a first multiple of the mixing frequency and mixing with a second multiple of the mixing frequency.

7. The method according to claim 1, wherein, Generating a σ-map involves performing a σ-mapping to identify variations in the returned signal data.

8. The method according to claim 7, wherein, Performing σ-mapping involves performing frame-to-frame comparisons to identify changes in the received ultrasound data between frames.

9. The method according to claim 8, wherein, Performing σ mapping also includes one or more of the following: integrated focus mixing, lateral elimination, difference summation, determination of lateral standard deviation and square.

10. The method according to claim 9, wherein, Performing σ-mapping also includes any one or more of the following: multiplying two ultrasound data streams, and performing frame elimination.

11. The method according to any one of claims 1, 7, 8, 9 or 10, wherein, Performing the target best-fit process involves performing a best-fit process to identify blobs that best match a set of target space criteria.

12. The method according to claim 11, wherein, Performing target detection includes generating beam histograms and generating frame histograms.

13. The method according to claim 10, wherein, Performing object detection involves applying adaptive thresholds.

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

15. The method according to claim 10, wherein, Performing target detection includes generating connectivity graph data, which represents connectivity information between units along at least two axes that are perpendicular to each other.

16. The method of claim 10, wherein, Performing target detection includes at least one of the following: calculating the distance from each of the multiple cells to the edge of the spot, and smoothing the calculated distance by filtering outbound regions.

17. The method according to claim 10, wherein, Performing object detection includes any one or more of the following: performing σ-threshold removal by removing regions based on a σ threshold; performing region removal by removing regions based on σ and B content; and performing isolated item removal by removing isolated blobs.

18. The method according to claim 10, wherein, Performing object detection involves recalculating the distance without removing values.

19. The method according to claim 10, wherein, Performing object detection includes any one or more of the following: determining the centroid of the blob; performing centroid reduction; performing centroid tracking; and performing centroid merging.

20. The method according to any one of claims 1 to 4, 6 to 10, or 13 to 19, wherein, The return signal processing chain processes a series of return signals including any one or more of the following: focus blending and performing scan conversion.

21. The method according to claim 20, wherein, The processing of a series of return signals via the return signal processing chain also includes visual and / or auditory presentation marker location information.

22. The method according to claim 21, wherein, Visual and / or auditory representation of marker localization information includes visual representations of the marker material relative to anatomical structures.

23. The method according to claim 21, wherein, Visual and / or auditory representation of marker localization information includes an auditory representation of the motion of the ultrasound probe relative to the marker's center.

24. The method according to any one of claims 1 to 4, 6 to 10, 13 to 19, or 21 to 23, wherein, A set of drive signals is generated via the transmitting portion of the ultrasound system, including: Generate a drive signal with a nominal pulse repetition frequency; A variation in power amplitude is introduced between at least some pulses of the integrated pulse of the drive signal; and The drive signal, which introduces a power amplitude variation, is provided to the at least one ultrasonic transducer to cause the at least one ultrasonic transducer to emit an ultrasonic signal with a power amplitude variation.

25. The method according to any one of claims 1 to 4 or 6 to 23, or claims 1 to 4 or 6 to 10 or 13 to 19 or 21 to 23, wherein, A set of drive signals is generated via the transmitting portion of the ultrasound system, including: Generate a drive signal with a nominal pulse repetition frequency; Introduce one or more of the following changes: the amplitude of the driving signal, the fundamental frequency, or the pulse repetition frequency; and A drive signal with introduced variation is provided to at least one ultrasonic transducer so that the at least one ultrasonic transducer emits an ultrasonic signal with that variation.

26. An ultrasound system, comprising: The transmitting section generates a set of drive signals and provides them to an ultrasonic probe having at least one ultrasonic transducer, so that the at least one ultrasonic transducer emits ultrasonic energy in the form of an integrated pulse, the corresponding integrated pulse being emitted along a corresponding one of the multiple beams and at multiple focal depths. as well as The receiving section processes a series of return signals according to any one of claims 1 to 20, the series of return signals representing the ultrasonic energy detected by the ultrasonic probe.

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

28. An ultrasound system, comprising: The transmitting section generates a set of drive signals and provides them to an ultrasonic probe having at least one ultrasonic transducer, so that the at least one ultrasonic transducer emits ultrasonic energy in the form of an integrated pulse, the corresponding integrated pulse being emitted along a corresponding one of the multiple beams and at multiple focal depths. as well as The receiving section includes a return signal processing chain that processes a series of return signals representing ultrasound energy detected by the ultrasound probe, wherein the return signal processing chain performs target detection, the target detection including generating a σ-map indicating variations between return signal data frames, and performing a target best-fit process based at least in part on the σ-map to detect the presence of a response signal from a tissue marker.

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

30. The ultrasonic system according to claim 28, wherein, The return signal processing chain mixes the return signal with a first multiple of the 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. The ultrasonic system according to claim 28, wherein, The return signal processing chain mixes the return signal with twice the fundamental frequency of the ultrasound, and mixes the return signal with 1.5 times the fundamental frequency of the ultrasound.

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

33. The ultrasound system according to claim 29, wherein, The return signal processing chain performs envelope detection on each signal generated by mixing with a first multiple of the mixing frequency and mixing with a second multiple of the mixing frequency.

34. The ultrasound system according to claim 28, wherein, To generate the σ-graph, the returning signal processing chain performs σ mapping.

35. The ultrasound system according to claim 34, wherein, In order to perform σ-mapping, the return signal processing chain performs frame-to-frame comparisons to identify changes in the received ultrasound data between frames.

36. The ultrasound system according to claim 35, wherein, To perform the σ-mapping, the returning signal processing chain performs one or more of the following operations: integrated focus mixing, lateral cancellation, difference summation, determination of lateral standard deviation, and squaring.

37. The ultrasound system according to claim 36, wherein, To perform σ-mapping, the return signal processing chain also forms any one or more of the following: multiplication of two ultrasound data streams and frame cancellation.

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

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

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

41. The ultrasound system according to claim 37, wherein, To perform target detection, the return signal processing chain performs focus merging to combine ultrasound datasets from two or more focus levels.

42. The ultrasound system according to claim 37, wherein, In order to perform target detection, the return signal processing chain generates connection graph data, which represents connection information between units along at least two axes that are perpendicular to each other.

43. The ultrasound system according to claim 37, wherein, In order to perform target detection, the return signal processing chain performs at least one of the following operations: calculates the distance from each of the multiple cells to the edge of the blob, and smooths the calculated distance by filtering outbound regions.

44. The ultrasound system according to claim 37, wherein, To perform object detection, the return signal processing chain performs one or more of the following: performing σ-threshold removal by removing regions based on a σ-threshold; performing region removal by removing regions based on σ and B content; and performing isolated item removal by removing isolated blob items.

45. The ultrasound system according to claim 37, wherein, In order to perform target detection, the return signal processing chain recalculates the distance without discarding any values.

46. ​​The ultrasound system according to claim 37, wherein, To perform target detection, the return signal processing chain performs any one or more of the following: determining the centroid of the blob; performing centroid reduction; performing centroid tracking; and performing centroid merging.

47. The ultrasonic system according to any one of claims 28 to 31 or 33 to 46, wherein, The return signal processing chain performs any one or more of the following: focus blending and scan conversion.

48. The ultrasound system according to claim 47, wherein, The return signal processing chain presents marker location information visually and / or audibly.

49. The ultrasound system according to claim 48, wherein, In order to present the marker localization information visually and / or aurally, the return signal processing chain presents a visual representation of the marker core relative to the visual representation of the anatomical structure.

50. The ultrasonic system according to claim 48, wherein, In order to present marker location information visually and / or audibly, the return signal processing chain presents an auditory representation of the motion of the ultrasound probe relative to the marker's center of mass.

51. The ultrasonic system according to any one of claims 28 to 31 or 33 to 50, wherein, To generate a set of driving signals, the transmitting section of the ultrasound system: Generate a drive signal with a nominal pulse repetition frequency; A variation in power amplitude is introduced between at least some of the integrated pulses of the drive signal; as well as A drive signal with an introduced power amplitude variation is provided to the at least one ultrasonic transducer to cause the at least one ultrasonic transducer to emit an ultrasonic signal with a power amplitude variation.

52. The ultrasonic system according to any one of claims 28 to 31 or 33 to 50, wherein, To generate a set of driving signals, the transmitting section of the ultrasound system: Generate a drive signal with a nominal pulse repetition frequency; Introduce one or more of the following changes: the amplitude of the driving signal, the fundamental frequency, or the pulse repetition frequency; and A drive signal with introduced variation is provided to the at least one ultrasonic transducer so that the at least one ultrasonic transducer emits an ultrasonic signal with said variation.

53. A marker for marking tissues, the marker comprising: gel; The detectable object carried by the gel can be detected by an imaging method different from ultrasound; as well as Multiple ultrasonic reflective elements carried by a gel, which are suspended in a hydrated gel, wherein the ultrasonic reflective elements can move freely in at least one dimension to a sufficient degree or distance to enhance any scattered return from the ultrasonic reflective elements in response to ultrasonic interrogation by the marker.

54. The marker according to claim 53, wherein, When the gel is hydrated, the plurality of ultrasonic reflective elements carried in the suspension are free to perform at least one of the following operations: vibrate, oscillate, or preferably move randomly to a sufficient degree or distance in at least two or more dimensions to enhance any scattered return from the ultrasonic reflective elements in response to an ultrasonic interrogation of the marker.

55. The marker according to claim 53, wherein, When the gel is hydrated, the plurality of ultrasonic reflective elements carried in the suspension can move freely to a sufficient degree or distance with changes in velocity to enhance any scattering return from the ultrasonic reflective elements in response to ultrasonic interrogation of the marker.

56. The marker according to claim 53, wherein, The plurality of ultrasonic reflective elements are located in a plurality of aggregates or clusters within the ultrasonic reflective elements, and are carried in a suspended state within the gel.

57. The marker according to claim 56, wherein, When the gel is hydrated, the aggregates or clusters of the plurality of ultrasonic reflective elements carried in the suspension can move freely to a sufficient degree or distance with changes in velocity to enhance any scattering return from the ultrasonic reflective elements in response to the ultrasonic interrogation of the marker.

58. The marker according to claim 53, wherein, The gel includes or is composed of hydrogels.

59. The marker according to claim 53, wherein, The gel includes or is composed of natural hydrogels.

60. The marker according to claim 53, wherein, The gel includes or is composed of artificial hydrogels.

61. The marker according to claim 53, wherein, The gel is at least partially cross-linked.

62. The marker according to claim 61, wherein, The degree of cross-linking of the gel allows the ultrasonic reflective element to freely perform at least one of the following operations: vibration, oscillation, or preferably random movement relative to each other in at least two or more dimensions to a sufficient extent or distance to enhance any scattering return from the ultrasonic reflective element in response to the ultrasonic interrogation of the marker.

63. The marker according to claim 53, wherein, The plurality of ultrasonic reflective elements are composed of or include a plurality of porous or mesoporous shells, each porous or mesoporous shell having a main cavity and a plurality of holes in fluid communication with the cavity.

64. The marker according to claim 53, wherein, The plurality of ultrasonic reflective elements are composed of or include a plurality of porous or mesoporous particles, each porous or mesoporous particle comprising a plurality of pores isolated from each other.

65. The marker according to claim 53, wherein, The plurality of ultrasonic reflective elements are composed of or include silicon dioxide.

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

67. The marker according to claim 53, wherein, The plurality of ultrasonic reflective elements are dispersed through the gel in the form of a colloidal dispersion.

68. The marker according to any one of claims 53 to 67, wherein, Each of the plurality of ultrasonic reflective elements has an irregular surface.

69. The marker according to claim 68, wherein, Each of the plurality of ultrasonic reflective elements includes gas in the aperture or cavity of the ultrasonic reflective element.

70. The marker according to claim 69, wherein, Each of the plurality of ultrasonic reflective elements includes a hydrophobic coating that prevents liquid from entering the hole or cavity.

71. The marker according to claim 70, wherein, Each of the plurality of ultrasonic reflective elements includes a hydrophobic coating that prevents liquid from entering the hole or cavity.

72. The marker according to claim 71, wherein, The hydrophobic coating prevents liquid from entering the pores or cavities for at least a 9-month extension period.

73. The marker according to claim 68, wherein, The gel is at least one of dehydration or freeze-drying, until it is implanted into body tissue.

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

75. The marker according to claim 53, wherein, The combination of surface roughness, material properties of the material including the ultrasonic reflector, porosity in the ultrasonic reflector, gas trapped by the ultrasonic reflector, size of the ultrasonic reflector, size of the aggregate or cluster of ultrasonic reflectors and their degrees of freedom of motion enhances the backscattering response to ultrasound.

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