Ultrasonic marker detection, markers, and associated systems, methods, and articles

Abstract

Markers for body tissue take a variety of forms and may include multiple ultrasound reflective elements (e.g., a hollow shell filled with air) and hydrogels that incorporate ultrasound reflective elements. The hydrogels may be natural or artificial and may be cross-linked. The ultrasound system advantageously injects a change in the drive signal that changes the frequency or phase of the ultrasound interrogation signal relative to the nominal frequency or nominal phase. The amount of change is preferably one to six orders of magnitude smaller than the nominal frequency or phase. The ultrasound system is capable of presenting or detecting flicker artifacts caused by the interaction of the changing interrogation signal with the ultrasound reflective elements, at least in the Doppler operating mode.

Description

Technical Field

[0001] The present disclosure generally relates to ultrasonic detection of markers in body tissue, and also to markers and associated systems, methods, articles of manufacture, and / or kits that can, for example, facilitate detection of edges of body tissue (e.g., abnormal body tissue) for monitoring, biopsy, resection, or ablation. Background Art

[0002] Related technical description

[0003] Various types of markers are used to mark body tissues to be monitored (or biopsied, excised, or ablated) over time. For example, some markers can allow or enhance visual detection by a surgeon. Some markers allow detection via various energy emission imaging modalities, such as ultrasound imaging, radiographic imaging (such as X-ray imaging or magnetic resonance imaging (MRI)). These different imaging modalities are typically used in different scenarios, and markers detectable under various visual detection or imaging modalities typically require different physical properties in order to be detectable.

[0004] Some markers may be permanent, while other markers may be absorbed by the body over a period of time. For example, it may be useful to mark a portion of body tissue for a considerable period of time (e.g., several months, a year) for subsequent evaluation or testing.

[0005] Markers are needed that are detectable via ultrasound and an additional imaging modality, and that, optionally, can be absorbed over time.

[0006] There is also a need for improved imaging techniques that do not use ionizing radiation, such as improved ultrasound imaging techniques, which can enhance the detection of markers in body tissue and / or the detection of certain body tissue edges (e.g., abnormal body tissue (e.g., tumors) or body tissue suspected of being abnormal). Summary of the invention

[0007] The present disclosure generally relates to ultrasonic detection of markers in body tissue, and also to detectable markers and associated systems, methods, articles and / or kits that can, for example, facilitate more accurate detection of tissue to be monitored, biopsied, resected, or ablated than would otherwise be possible using conventional methods.

[0008] The marker for body tissue takes a variety of forms and may include a plurality of ultrasonic reflective elements and a hydrogel in combination with the ultrasonic reflective elements. For example, the ultrasonic reflective element may take the form of a hollow shell. The cavity of the hollow shell may be filled with a fluid, such as a gas (such as air, a liquid, or a combination of a gas and a liquid (e.g., steam)), and may advantageously be free of perfluorocarbons. The hollow shell may be porous and may be coated with a hydrophobic coating to at least temporarily seal the pores to prevent or delay the release of the fluid (e.g., gas) from the cavity to the outside of the hollow shell. The ultrasonic reflective element may include or be composed of one or more forms of silica. The hydrogel may be natural (e.g., gelatin) or artificial hydrogel (e.g., polyethylene glycol (PEG)). The hydrogel may be partially or completely cross-linked. The hydrogel may be designed to be absorbed by the body over a period of time, or may alternatively be non-absorbable.

[0009] The ultrasound system advantageously injects a change in the drive signal that changes the frequency or phase of the ultrasound interrogation signal relative to the nominal frequency or nominal phase. The amount of change is preferably one to six orders of magnitude smaller than the nominal frequency or phase. The change may be periodic, may follow a defined pattern, or may be pseudo-random or random. The ultrasound system may present or detect flicker artifacts, at least in the Doppler operating mode, caused by the interaction of the changing interrogation signal with the ultrasound reflective elements.

[0010] The marker and ultrasound system may be provided as a kit, wherein during a Doppler mode of operation, the hollow shell ultrasound reflective element is particularly effective in producing scintillation artifacts when receiving an ultrasound interrogation signal having a frequency or phase variation (preferably in the range of one to six orders of magnitude less than the nominal frequency or phase). BRIEF DESCRIPTION OF THE DRAWINGS

[0011] In the drawings, the same reference numerals represent similar elements or actions. The sizes and relative positions of the elements in the drawings are not necessarily drawn to scale. For example, the shapes and angles of the various elements are not drawn to scale, and some of the elements are arbitrarily enlarged and positioned to improve the readability of the drawings. In addition, the particular shape of the drawn element is not intended to convey any information about the actual shape of the particular element, and the particular shape is selected only for ease of identification in the drawings.

[0012] Figure 1 is an isometric view of a marker for marking body tissue according to an illustrated embodiment, the marker comprising a plurality of ultrasound reflective elements and a hydrogel carrier, with an enlarged view detailing that one of the ultrasound reflective elements includes a contrast agent carried by the ultrasound reflective element to enhance detection of other imaging modalities.

[0013] Figure 2is an isometric view of a marker for marking body tissue according to an illustrated embodiment, the marker comprising multiple ultrasound reflective elements, a hydrogel, and an optional thread, with an enlarged view detailing that one of the ultrasound reflective elements includes a contrast agent and a hydrophobic coating, the contrast agent being carried by the ultrasound reflective element to enhance detection of other imaging modes.

[0014] Figure 3 is a schematic diagram of an analog pulsed ultrasound imaging system according to at least one illustrated embodiment, which introduces variations in a nominal pulse repetition frequency into a drive signal that drives an ultrasound transducer, and which is operable to detect flicker artifacts in a received return signal in a Doppler operating mode (e.g., a color Doppler mode), the flicker artifacts being caused by the interaction of an ultrasound signal having a varying pulse repetition frequency with at least a portion of a marker that is reflected by the ultrasound and preferably has an irregular surface.

[0015] Figure 4 is a schematic diagram of a digital pulse ultrasound imaging system according to at least one illustrated embodiment, which introduces variations in a nominal pulse repetition frequency into a drive signal that drives an ultrasound transducer, and which is operable to detect flicker artifacts in a received return signal in a Doppler operating mode (e.g., a color Doppler mode), the flicker artifacts being produced by the interaction of an ultrasound signal having a varying pulse repetition frequency with at least a portion of a marker that is reflected by the ultrasound and preferably has an irregular surface.

[0016] Figure 5 is a schematic diagram of a continuous wave (CW) ultrasound imaging system according to at least one illustrated embodiment, which introduces variations in a nominal pulse repetition frequency into a drive signal that drives an ultrasound transducer, and which is operable to detect flicker artifacts in a received return signal in a Doppler operating mode (e.g., a color Doppler mode), the flicker artifacts being caused by the interaction of an ultrasound signal having a varying pulse repetition frequency with at least a portion of a marker that is reflected by the ultrasound and preferably has an irregular surface.

[0017] Figure 6 is a block diagram of a signal processing algorithm that can be implemented in hardware, software, and / or firmware according to at least one illustrative embodiment.

[0018] Fig. 7A is a graph illustrating an exemplary raw analog-to-digital (ADC) signal in the time domain produced by an ADC according to at least one illustrative embodiment.

[0019] Figure 7Bis a graph illustrating an exemplary raw analog-to-digital (ADC) signal in the frequency domain produced by an ADC according to at least one illustrative embodiment.

[0020] Fig. 8A is a graph illustrating an exemplary bandpass filtered ADC signal in the time domain after bandpass filtering the raw ADC signal according to at least one illustrative embodiment.

[0021] Figure 8B is a graph illustrating an exemplary bandpass filtered ADC signal in the frequency domain after bandpass filtering the raw ADC signal according to at least one illustrative embodiment.

[0022] Fig. 9 is a graph illustrating a filter response for an exemplary bandpass filter according to at least one illustrative embodiment.

[0023] Fig. 10A is a graph illustrating an I / Q signal in the time domain output by an I / Q mixer after mixing with an I / Q reference signal according to at least one illustrative embodiment.

[0024] Fig. 10B is a graph illustrating an I / Q signal in the frequency domain output by an I / Q mixer after mixing with an I / Q reference signal according to at least one illustrative embodiment.

[0025] Fig.11A is a graph illustrating a low pass filtered I / Q signal in the time domain output by a low pass filter according to at least one illustrative embodiment.

[0026] Fig. 11B is a graph illustrating a low pass filtered I / Q signal in the frequency domain output by a low pass filter according to at least one illustrative embodiment.

[0027] Fig.12 is a graph illustrating a filter response of an exemplary low pass filter, for example, selecting a frequency less than 1 MHz, according to at least one illustrative embodiment.

[0028] Fig.13A is a graph illustrating a downsampled I / Q signal in the time domain output by a downsampler according to at least one illustrative embodiment.

[0029] Fig. 13B is a graph illustrating a downsampled I / Q signal in the frequency domain output by a downsampler according to at least one illustrative embodiment.

[0030] Fig.14A is a graph illustrating downsampled I / Q data resulting from downsampling according to at least one illustrative embodiment.

[0031] Fig. 14B is a graph illustrating phase degrees of downsampled I / Q data according to at least one illustrative embodiment.

[0032] Fig. 14C is a graph illustrating normalized amplitude of downsampled I / Q data according to at least one illustrative embodiment. DETAILED DESCRIPTION

[0033] In the following description, some specific details are set forth to provide a full understanding of the various disclosed embodiments. However, those skilled in the relevant art will recognize that the embodiments can be practiced without one or more of these specific details, or using other methods, components, materials, etc. In other cases, well-known structures associated with microcontrollers, piezoelectric devices or transducers, power supplies (such as DC / DC converters), radios (i.e., transmitters, receivers, or transceivers), computing systems including client and server computing systems, networks (e.g., cellular, packet switching), and other communication channels are not shown or described in detail to avoid unnecessarily obscuring the description of the embodiments.

[0034] Unless the context requires otherwise, in the following description and claims, the word "comprise" and variations such as "comprises" and "comprising" are to be interpreted in an open and inclusive sense, i.e., "including but not limited to."

[0035] Throughout this specification, references to "one embodiment" or "an embodiment" refer to a particular feature, structure, or characteristic described in conjunction with the embodiment being included in at least one embodiment. Thus, the phrases "in one embodiment" or "in an embodiment" appearing in multiple places throughout this specification do not necessarily all refer to the same embodiment. Furthermore, particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0036] Unless the content clearly indicates otherwise, the singular forms "a", "an", and "the" used in this specification and the drawings include plural referents. It should also be noted that the term "or" is generally used to include the meaning of "and / or" unless the content clearly indicates otherwise.

[0037] The titles and abstracts of the disclosures provided herein are for convenience only and are not used to interpret the scope or meaning of the embodiments.

[0038] In particular, novel tissue markers and ultrasound techniques, systems, methods, and articles are described herein to advantageously mark tissue for later evaluation, resection, and / or ablation. For example, this can be used to more accurately define the margins of abnormal or suspicious tissue (e.g., tumors) in body tissue.

[0039] Figure 1 A marker 100 for marking body tissue is shown in accordance with at least one illustrative embodiment.

[0040] In at least one embodiment, the marker 100 includes a plurality of ultrasound reflective elements 102 (only one is labeled) carried by a hydrogel carrier 104. The hydrogel carrier 104 binds the plurality of ultrasound reflective elements 102 together.

[0041] The hydrogel carrier 104 can take various forms. The hydrogel carrier 104 can include a natural hydrogel, such as gelatin. The hydrogel carrier 104 can include an artificial hydrogel, such as a polyvinyl alcohol (PVA) hydrogel or a polyethylene glycol (PEG) hydrogel. The hydrogel carrier 104 can include a combination of a natural hydrogel (e.g., gelatin) and an artificial hydrogel (e.g., a PVA hydrogel, a PEG hydrogel).

[0042] In at least some embodiments, the hydrogel carrier 104 is an at least partially cross-linked hydrogel. In at least some embodiments, the hydrogel carrier 104 is gelatin, such as a cross-linked gelatin. In at least some embodiments, the hydrogel carrier 104 is a PVA hydrogel, such as a cross-linked PVA hydrogel. In at least some embodiments, the hydrogel carrier 104 is a PEG hydrogel, such as a cross-linked PEG hydrogel. In at least some embodiments, the hydrogel carrier 104 includes a combination of natural hydrogels and artificial hydrogels, such as respective gels coupled to each other.

[0043] The hydrogel carrier 104 can be non-absorbable by the body (e.g., persisting for more than 60 years or more), or can be absorbed by the body over a period of time. In the case of being absorbable, the hydrogel carrier 104 can be designed (e.g., via the degree or strength of cross-linking) to persist in the body for a period of time, such as persisting for hours, days, a week or weeks, a month or months, or even a year or years. In at least some embodiments, the outer or exposed portion of the absorbable hydrogel carrier 104 can be absorbed faster than the more internal portion of the hydrogel carrier when implanted, and the absorption occurs when the various portions of the hydrogel carrier 104 are exposed to body tissues including body fluids. In at least some embodiments, the hydrogel carrier 104 can be designed (e.g., controlled cross-linking profiles) to make some portions absorb faster than other portions and / or to ensure that some portions persist longer than other portions. Therefore, various absorption profiles can be formed on or through the hydrogel carrier.

[0044] Each ultrasound reflective element is highly reflective to ultrasound. Each ultrasound reflective element preferably has an irregular surface, for example, a rough outer surface to cause scattering or diffusion of ultrasound energy. The ultrasound reflective element 102 may be nanometer-sized (eg, 1.8 micrometers to about 2.2 micrometers).

[0045] The ultrasound reflective element 102 may take any of a variety of forms.

[0046] In at least one embodiment, each ultrasound reflective element comprises a particle that is not a hollow shell but a solid particle or alternatively a porous non-spherical particle. For example, each ultrasound reflective element may include a corresponding particle that includes or consists of silicon dioxide without a hollow internal cavity. Each particle may include one or more layers ( Figure 1 106 to enhance detection via modalities other than ultrasound imaging, as described below. Alternatively, one or more ultrasound reflective elements may include or consist of one or more contrast agents.

[0047] The contrast agent 106 may, for example, include one or more contrast agents that enhance visual detection or detection using an X-ray or MRI imaging modality. For example, some or all of the ultrasound reflective elements 102 may include a dye to enhance detection by direct visual observation. The dye may advantageously be a fluorescent dye. For example, the dye may include or be composed of methylene blue. For another example, some or all of the ultrasound reflective elements 102 may include or be composed of a radiopaque material (e.g., gold, platinum, tantalum, bismuth, barium, etc.). For another example, some or all of the ultrasound reflective elements 102 may include or be composed of an MRI imaging material (e.g., a gadolinium that includes a compound, such as gadolinium DTPA, ferrous gluconate, ferrous sulfate, etc.).

[0048] Alternatively, in addition to the ultrasound reflecting element 102, one or more contrast agents 106, for example, the contrast agents 106 noted above or wires (e.g., helically wound metal wires) or other radiopaque elements (such as radiopaque clips) may be incorporated into or around the hydrogel carrier 104.

[0049] 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 multilayer hollow shell, such as a shell having an inner layer and an outer layer. Each hollow shell is highly reflective to ultrasound. Each hollow shell preferably has an irregular surface, such as a rough outer surface to cause scattering or diffusion of ultrasound energy. The hollow shell can be nanometer-sized.

[0050] In at least some embodiments, each hollow shell may include, or alternatively consist of, silicon dioxide or titanium dioxide. Some techniques for forming nanometer-sized hollow shells are described in, for example, 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 / 706446; U.S. Patent Application 62 / 135653; U.S. Patent Application 15 / 559764; 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.

[0051] The hollow shell or one or more layers of the hollow shell may contain one or more contrast agents, such as those noted above for enhancing visual, radiological or MRI detection.

[0052] In at least some embodiments, the cavity of at least one hollow shell contains a fluid, i.e., a gas, a liquid, or a combination or mixture of a gas and a liquid. The gas can be in the form of a material, and the liquid can be in 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 phases. For example, the combination or mixture of gas and liquid can take the form of steam, which is either in a static state or is subjected to ultrasonic influences of a certain threshold energy level causing heating. The cavity of at least one hollow shell can, for example, contain air. Alternatively, the cavity of at least one hollow shell can contain an inert gas (e.g., nitrogen, argon). The cavity preferably does not have any perfluorocarbon, for example, whether in gaseous and / or liquid form.

[0053] Each hollow shell may be porous. Where the hollow shell contains a fluid (ie, a gas, a liquid, or a combination or mixture of gas and liquid), the marker 100 may optionally include a coating (preferably a hydrophobic coating) that at least temporarily seals one or more of its pores.

[0054] In some embodiments, the hydrogel can be swellable, for example when implanted into body tissue. In some embodiments, the length of the marker 100 in the unexpanded state can be about 2 mm to about 40 mm, and its transverse dimension can be about 0.5 mm to about 2 mm. The dimensional expansion ratio of the marker from the dry unexpanded state to the water-saturated expanded state can be about 1:1.5 to about 1:10. The dimensional expansion ratio of the marker 100 from the dry unexpanded state to the water-saturated expanded state can be about 1:2 to about 1:3.

[0055] Figure 2 A marker 200 for marking body tissue is shown, according to at least one illustrative embodiment.

[0056] In at least one embodiment, the marker 200 includes at least one hollow shell 202, and preferably includes a plurality of hollow shells 202 (only one is marked). Each hollow shell 202 has at least one outer wall forming a cavity. In at least some embodiments, the hollow shell 202 is a multi-layer hollow shell, such as a shell having an outer layer 202a, an inner layer 202b and a cavity 202c. Each hollow shell 202 is highly reflective to ultrasound. Each hollow shell 202 preferably has an irregular surface, such as a rough outer surface to cause scattering or diffusion of ultrasonic energy. The hollow shell 202 can be nanometer-sized (e.g., 1.8 microns to about 2.2 microns).

[0057] In at least some embodiments, each hollow shell 202 may include, or alternatively consist of, silicon dioxide or titanium dioxide. Some techniques for forming nano-sized hollow shells 202 are described in, for example, U.S. Patent Application Nos. 60 / 955,678; 61 / 034,468; 12 / 673,224 (now U.S. Patent No. 8,440,229); International Patent Application Nos. PCT / US2008 / 072972; 13 / 866,940 (now U.S. Patent No. 9,220,685); 15 / 722,436; 61 / 707,794; International Patent Application Nos. U.S. Patent Application Nos. 15 / 706,446; 62 / 135,653; 15 / 559,764; International Patent Application No. PCT / US2016 / 23492; 62 / 483,274; 62 / 645,677; 15 / 946,479; and International Patent Application No. PCT / US2018 / 26291 (published as WO2018 / 187594).

[0058] In at least some embodiments, the cavity 202c of at least one hollow shell 202 contains a fluid, or a gas, or a combination or mixture of a gas and a fluid. For example, the cavity 202c of at least one hollow shell 202 may contain air. Alternatively, the cavity 202c of at least one hollow shell 202 may contain an inert gas (e.g., nitrogen, argon). The cavity 202c preferably does not have any perfluorocarbons, for example, whether in gaseous and / or liquid form.

[0059] Each hollow shell 202 may be porous. In the case where the hollow shell 202 contains a fluid (i.e., a gas, a liquid, or a mixture of a gas and a liquid), the marker 200 may optionally include a coating that at least temporarily seals one or more of its pores, preferably a hydrophobic coating 208. The hydrophobic coating 208 may take the form of a hydrophobic polymer, such as a hydrophobic polymer including octyltriethoxysilane.

[0060] As described below, one or more layers 202a, 202b of the hollow shell 202 may include one or more contrast agents 206a, 206b to enhance detection via modalities other than ultrasound imaging.

[0061] The contrast agent may, for example, include one or more contrast agents that enhance visual detection or use an X-ray or MRI imaging modality. For example, some or all of the ultrasonic reflective elements 102 may include dye 206a (in the outermost layer 202a) to enhance detection by direct visual observation. The dye may advantageously be a fluorescent dye. For example, the dye may include or be composed of methylene blue. For another example, some or all of the ultrasonic reflective elements 102 may include or be composed of radiopaque materials (e.g., gold, platinum, tantalum, bismuth, barium, etc.) and / or MRI imaging materials (e.g., gadolinium including compounds, such as gadolinium DTPA, ferrous gluconate, ferrous sulfate, etc.), which are collectively referred to as 202b.

[0062] As described above, the marker 200 may preferably include a plurality of hollow shells 202. The marker 200 may also include a hydrogel 204 that combines the plurality of hollow shells 202 together. In at least some embodiments, the hydrogel 204 is a hydrogel that is at least partially cross-linked. In at least some embodiments, the hydrogel 204 is gelatin, such as cross-linked gelatin. The hydrogel 204 may take a variety of forms. For example, the hydrogel may be a natural hydrogel (e.g., gelatin) or an artificial hydrogel (e.g., polyvinyl alcohol (PVA) hydrogel, polyethylene glycol (PEG) hydrogel). The hydrogel 204 may be non-absorbable by the body (e.g., persisting for more than 60 years or longer), or may be absorbed by the body over a period of time. In the case of being absorbable, the hydrogel 204 may be designed (e.g., via the degree or strength of cross-linking) to persist in the body for a period of time, such as persisting for hours, days, a week or weeks, a month or months, or even a year or years. In at least some embodiments, the outer or exposed portions of the absorbable hydrogel can absorb faster when implanted than more internal portions of the hydrogel, which occurs when the various portions of the hydrogel are exposed to body tissue including body fluids. In at least some embodiments, the hydrogel 204 can be designed (e.g., controlled cross-linking profiles) to cause some portions to absorb faster than other portions and / or to ensure that some portions persist longer than other portions. Thus, various absorption profiles can be formed on or through the hydrogel 204.

[0063] In addition to the hollow shell 202, one or more contrast agents 206a, 206b, such as those noted above or radiopaque elements (eg, radiopaque, helically wound wire 210, radiopaque clips), may be incorporated into or around the hydrogel carrier.

[0064] In some embodiments, the hydrogel can be swellable, for example when implanted into body tissue. In some embodiments, the length of the marker 200 in the unexpanded state can be about 2 mm to about 40 mm, and its transverse dimension can be about 0.5 mm to about 2 mm. The dimensional expansion ratio of the marker from the dry unexpanded state to the water-saturated expanded state can be about 1:1.5 to about 1:10. The dimensional expansion ratio of the marker 200 from the dry unexpanded state to the water-saturated expanded state can be about 1:2 to about 1:3.

[0065] Figure 3 Shown is a marker 300 implanted in body tissue 302 and an analog pulsed Doppler ultrasound system 304 including an ultrasound probe or transducer array 306 positioned to detect the marker 300 , according to at least one illustrative embodiment.

[0066] The analog pulse Doppler ultrasound system 304 includes a transmit portion 308 and a receive portion 310. The transmit portion 308 generates pulses and drives the ultrasound probe or transducer array 306 to transmit ultrasound energy. The receive portion 310 receives signals representing ultrasound energy returned from objects in the field of view of the ultrasound probe or transducer array 306 and processes the return signals based on one or more operating modes (e.g., A mode, B mode, M mode, Doppler color mode, Doppler power mode). In some embodiments, the analog pulse Doppler ultrasound system 304 will alternate between capturing B mode frames and Doppler color or power mode frames, such as changes in pulse repetition that occur during the Doppler operating mode but not during the B operating mode.

[0067] The analog pulse Doppler ultrasound system 304 includes a master clock or oscillator 312 that outputs a timing signal. The timing signal output by the master clock or oscillator 312 sets or is used to set a nominal pulse repetition frequency, i.e., the frequency at which the ultrasound pulses are repeated. In at least some embodiments, the nominal pulse repetition frequency can be set by an operator, at least within a certain defined range. In other embodiments, the nominal pulse repetition frequency can be a fixed characteristic of a particular analog pulse Doppler ultrasound system 304.

[0068] The transmitting section 308 includes a variation circuit (VAR) 314 that introduces a variation in a clock signal provided by a master clock or oscillator 312, directly or indirectly (e.g., via a gate generator) introducing a variation relative to a nominal pulse repetition frequency into a drive signal for driving the ultrasound probe or transducer array 306 during the Doppler operating mode. The variation can be a variation in time or a variation in phase, and the variation is a variation over a period of time. For example, the variation can be achieved via one or more delay circuits or capacitors that delay the clock signal. For example, the delay circuit can have an adjustable delay, or two or more different delay circuits (each with a respective delay) can introduce delays of different durations to achieve the variation during the Doppler operating mode. The variation can be periodic, can follow a pattern, or can be pseudo-random, for example, generated via a pseudo-random number generator (also known as a random number generator (RNG)). The periodic variation can have a period or frequency different from the nominal pulse repetition frequency. The receiving section 310 can advantageously employ periodic variations or variations that follow a pattern. During the capture of one or more Doppler frames of ultrasound data, this variation may be introduced into the drive signal over a plurality of pulses transmitted during the Doppler mode of operation to intentionally introduce artifacts that are typically viewed as undesirable noise.

[0069] The variation is preferably at least one order of magnitude less than the nominal pulse repetition frequency, and more preferably two orders of magnitude, three orders of magnitude, four orders of magnitude, five orders of magnitude, or most preferably six orders of magnitude less than the nominal pulse repetition frequency.

[0070] The varying clock signal is provided to a gate generator 316, which is communicatively coupled via an amplifier 318 to drive the ultrasound probe or transducer array 306. The varying clock signal is also provided to the receiving portion 310, such as a set of mixers 320, and a set delay and duration circuit 322. The set delay duration circuit 322 is communicatively coupled to a second set of mixers 324 of the receiving portion 310, which feed into a set of range gates 326, which in turn feed into a set of holding and filtering circuits 328 of the receiving portion 310.

[0071] The receiving section 310 receives signals representing ultrasonic energy returned from objects in the field of view of the ultrasonic probe or transducer array 306, and the amplifier 330 of the receiving section 310 amplifies the return signal. The amplified return signal is filtered by the matched filter 332. The set of mixers 320 then mixes in the varying clock signal, and the result is low pass filtered by a set of low pass filters 334 to be provided for orthogonal processing via a second set of mixers 324, a range gate 326, and a hold and filter circuit 328.

[0072] Figure 4Shown is a marker 400 implanted in body tissue 402 and a digital pulsed Doppler ultrasound system 404 including an ultrasound probe 406 positioned to detect the marker 400 in accordance with at least one illustrative embodiment.

[0073] The digital pulse Doppler ultrasound system 404 includes a transmitting portion 408 and a receiving portion 410. The transmitting portion 408 generates pulses and drives the ultrasound probe or transducer array 406 to transmit ultrasound energy. The receiving portion 410 receives signals representing ultrasound energy returned from objects in the field of view of the ultrasound probe or transducer array 406, and processes the return signals based on one or more operating modes (e.g., A mode, B mode, M mode, Doppler color mode, Doppler power mode). In some embodiments, the digital pulse Doppler ultrasound system 404 will alternate between capturing B mode frames and Doppler color or power mode frames, such as changes in pulse repetition that occur during the Doppler operating mode but not during the B operating mode.

[0074] The digital pulse Doppler ultrasound system 404 includes a master clock or oscillator 412 that outputs a timing signal. The timing signal output by the master clock or oscillator 412 sets or is used to set a nominal pulse repetition frequency, i.e., the frequency at which the ultrasound pulses are repeated. In some embodiments, the nominal pulse repetition frequency can be set by an operator, at least within a certain defined range. In other embodiments, the nominal pulse repetition frequency can be a fixed characteristic of a particular digital pulse Doppler ultrasound system 404.

[0075] The transmitting portion 408 includes a variation circuit (VAR) 414 that introduces a variation in the clock signal provided by the master clock or oscillator 412, directly or indirectly (e.g., via a gate generator) introducing a variation relative to the nominal pulse repetition frequency into the drive signal used to drive the ultrasound probe or transducer array 406 during the Doppler operating mode. The variation can be a variation in time or a variation in phase, and the variation is a variation over a period of time during the Doppler operating mode. For example, the variation can be achieved via one or more delay circuits that delay the clock signal. For example, the delay circuit can have an adjustable delay, or two or more different delay circuits (each with a respective delay) can introduce delays of different durations to achieve the variation. The variation can be periodic, can follow a pattern, or can be pseudo-random, for example, generated via a pseudo-random number generator (also known as a random number generator (RNG)). The periodic variation can have a period or frequency different from the nominal pulse repetition frequency. The receiving portion 410 can advantageously employ periodic variations or variations that follow a pattern. The variation is preferably at least one order of magnitude less than the nominal pulse repetition frequency, and more preferably two orders of magnitude, three orders of magnitude, four orders of magnitude, five orders of magnitude, or most preferably six orders of magnitude less than the nominal pulse repetition frequency.

[0076] The varying clock signal is provided to a gate generator 416, which is communicatively coupled via an amplifier 418 to drive the ultrasound probe or transducer array 406. The varying clock signal is also provided to a receiving portion 410, such as a set of mixers 420, and a set of digital-to-analog converters (ADCs) 422.

[0077] The receiving section 410 receives a signal representing ultrasonic energy returned from an object in the field of view of the ultrasonic probe or transducer array 406, and the amplifier 424 of the receiving section 410 amplifies the return signal. The matched filter 426 filters the amplified return signal. The set of mixers 420 then mixes in a varying clock signal, and the result is analog-to-digital converted by the ADC 422. The output from the ADC 422 is provided to a set of range gates 428 for digital signal processing.

[0078] Figure 5 Shown is a marker 500 implanted in body tissue 502 and a continuous wave Doppler ultrasound system 504 including an ultrasound probe or transducer array 506 positioned to detect the marker 500 in accordance with at least one illustrative embodiment.

[0079] The continuous wave Doppler ultrasound system 504 includes a transmitting portion 508 and a receiving portion 510. The transmitting portion 508 generates a continuous (e.g., sine wave, cosine wave) signal and drives the ultrasound probe or transducer array 506 to transmit ultrasound energy. The receiving portion 510 receives a signal representing ultrasound energy returned from an object in the field of view of the ultrasound probe or transducer array 506, and processes the return signal based on one or more operating modes (e.g., A mode, B mode, M mode, Doppler color mode, Doppler power mode). In some embodiments, the continuous wave Doppler ultrasound system 504 will alternate between capturing B mode frames and Doppler color or power mode frames, such as a change in pulse repetition that occurs during the Doppler operating mode but not during the B operating mode.

[0080] The continuous wave Doppler ultrasound system 504 includes a master clock or oscillator 512 that outputs a timing signal. The timing signal output by the master clock or oscillator 512 sets or is used to generate a continuous wave (e.g., a sine wave, a cosine wave). In some embodiments, the frequency of the continuous wave can be set by the operator at least within a certain defined range. In other embodiments, the frequency of the continuous wave can be a fixed characteristic of a particular ultrasound system 504.

[0081] The transmitting portion 508 includes a variation circuit (VAR) 514 that introduces a variation in the continuous wave signal provided by the master clock or oscillator 512, directly or indirectly introducing a variation of the continuous wave relative to the nominal frequency into the drive signal used to drive the ultrasound probe or transducer array 506 during the Doppler operating mode. The variation can be expressed as a variation in time or a variation in phase, and the variation is a variation over a period of time during the Doppler operating mode. For example, the variation can be achieved via one or more delay circuits that delay the clock signal. For example, the delay circuit can have an adjustable delay, or two or more different delay circuits (each with a respective delay) can introduce delays of different durations to achieve the variation. The variation can be periodic, can follow a pattern, or can be pseudo-random, for example, generated via a pseudo-random number generator (also called a random number generator (RNG)). The periodic variation can have a period or frequency different from the nominal pulse repetition frequency. The receiving portion 510 can advantageously employ periodic variations or variations that follow a pattern. The variation is preferably at least one order of magnitude less than the nominal pulse repetition frequency, and more preferably two orders of magnitude, three orders of magnitude, four orders of magnitude, five orders of magnitude, or most preferably six orders of magnitude less than the nominal pulse repetition frequency.

[0082] The varying continuous wave signal is also provided to the receiving portion 510, for example, to a set of mixers 520, which may be implemented in hardware, software and / or firmware.

[0083] The receiving section 510 receives a signal representing ultrasonic energy returned from an object in the field of view of the ultrasonic probe or transducer array 506, and an amplifier 530 of the receiving section 510 amplifies the return signal. A matched filter 532 filters the amplified return signal. The set of mixers 520 then mixes in the varying continuous wave signal, and the result is low pass filtered by a set of low pass filters 534. A phase shifter 535 shifts one of the signal paths to provide orthogonal processing, and a set of adders 537 produces separate Doppler outputs (e.g., forward flow; reverse flow).

[0084] In any Figure 3 , Figure 4 and Figure 5 In embodiments, images captured during the Doppler mode of operation may be presented superimposed with images captured during the B mode of operation to facilitate visualization of markers relative to various anatomical features of the body.

[0085] Figure 6 A signal processing algorithm 600 that can be implemented in hardware, software, and / or firmware according to at least one illustrated embodiment is shown. The hardware may, for example, include an analog-to-digital converter (ADC), a field programmable gate array (FPGA), and a computer system based on one or more processors, which employs one or more processors and memory or other non-transitory storage media. 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. The memory may, for example, include one or more of the following: a read-only memory (ROM), a random access memory (RAM), an EEPROM, a flash memory, and / or a register, etc. Other non-transitory storage media may, for example, include one or more of the following: a disk and an associated disk drive, an optical disk and an associated optical disk drive, and / or a solid-state drive (SSD), etc.

[0086] From the transducer ( Figure 6 Receive an analog transducer signal 602 (not shown). The received analog transducer signal 602 has a center frequency, for example, a center frequency of 3 MHz.

[0087] The received analog transducer signal 602 is digitized, for example, via an ADC 604. The ADC 604 may, for example, take the form of a 14-bit ADC with a sampling clock 605 of, for example, 12 MHz.

[0088] The raw ADC sampled data output by ADC 604 is processed by FPGA 606 (add Figure 6 ) is captured and transmitted to a processor-based computer system (represented by a dashed box) 608, for example, via a USB interface 610. Note that the FPGA 606 only captures the ADC sampled data and transmits the ADC sampled data to the processor-based computer system 608, without performing any operation on the ADC sampled data.

[0089] Fig. 7A and Figure 7B Examples of raw ADC signals 700a, 700b in the time domain and frequency domain are shown, respectively. In particular, Fig. 7A The original ADC signal 700a of the 750th to 850th samples is amplified. Figure 7B is the power spectral density estimate of the raw ADC signal 700b based on the FFT. It can be seen how the maximum power is centered at 3MHz, which is expected since the Tx frequency is 3MHz. At this point, the raw ADC signal has not been filtered yet.

[0090] Back to Figure 6 , the processor-based computer system 608 can perform the remaining signal processing operations. For example, software written in Python can operate on the collected raw ADC samples provided via the FPGA 606.

[0091] In the first signal processing operation, software executed by the processor-based computer system 608 can implement a bandpass filter 612 to remove out-of-band noise prior to the I / Q demodulation signal processing operation. For example, the bandpass filter 612 can have a passband of 2 MHz to 4 MHz.

[0092] Fig. 8A shows the raw ADC signal ( Fig. 7A ) is bandpass filtered ADC signal in time domain 800a after bandpass filtering (limited to acquired time samples 750 and 850, 1600 in total). Figure 8B shows the raw ADC signal ( Figure 7B ) after bandpass filtering. Note that Fig. 7A and Figure 7B , and how the frequency powers in the 0-2 and 4-6 MHz ranges are greatly reduced compared to the frequency powers shown in .

[0093] Fig. 9 A filter response 900 of an exemplary bandpass filter 612 is shown.

[0094] Back to Figure 6, software executed by the processor-based computer system 608 can implement an I / Q mixer 614 to perform demodulation signal processing operations. The I / Q mixer 614 mixes the output of the bandpass filter 612 with an I / Q reference signal, such as a 3 MHz I / Q reference signal 615. The frequency of the I / Q reference signal 615 can preferably be matched to the center frequency of the received transducer signal 602.

[0095] Fig. 10A An I / Q signal 1000a in the time domain output by the I / Q mixer 614 after mixing with an I / Q reference signal is shown, containing signals from the 750th to 850th samples. Fig. 10B The I / Q signal 1000b in the frequency domain output by the I / Q mixer 614 after mixing with the I / Q reference signal is shown. The mixed I / Q signal is centered around zero because the I / Q reference signal matches the frequency of the received signal. It is noteworthy that there is a very slight asymmetry between negative and positive frequencies.

[0096] Back to Figure 6 , software executed by the processor-based computer system 608 can implement a low-pass filter 616 to remove any dual-frequency components from the signal output by the I / Q mixer 614, leaving only the baseband components. Applying the low-pass filter obtains the envelope of the mixed signal. It is worth noting that this is why Fig.11A The lines in the time domain plot of look smooth, not like Fig. 10A For example, low pass filter 616 may have a passband set to 1 MHz.

[0097] Fig.11A A low pass filtered I / Q signal 1100a in the time domain output by the low pass filter 616 is shown.

[0098] Fig. 11B A low pass filtered I / Q signal 1100b in the frequency domain output by the low pass filter 616 is shown.

[0099] Fig.12 The filter 1200 response of an exemplary low pass filter 616 is shown, for example, selecting a frequency less than 1 MHz.

[0100] Back to Figure 6 , software executed by the processor-based computer system 608 can implement a downsampler 618 to reduce the data sampling rate. The downsampler 618 can reduce the data sampling rate from, for example, 12 MHz to 3 MHz, such that the data output from the low-pass filter 616 only has frequency components less than 1 MHz. Reducing the sampling rate advantageously reduces the amount of data required for processing without reducing the information content.

[0101] Fig.13A A downsampled I / Q signal 1300a in the time domain output by the downsampler 618 is shown. Fig. 13B A downsampled I / Q signal 1300b is shown in the frequency domain output by the downsampler 618. In the example shown, the low pass filtered I / Q data is advantageously downsampled by one quarter.

[0102] Back to Figure 6 , software executed by the processor-based computer system 608 may implement a phase calculation component or signal processing operation 620, wherein the phase of the downsampled I / Q signal is calculated for each sampling point of the downsampled I / Q data.

[0103] Back to Figure 6 , software executed by the processor-based computer system 608 may implement an amplitude calculation component or signal processing operation 622, wherein the amplitude of the downsampled I / Q signal is calculated for each sampling point of the downsampled I / Q data.

[0104] Fig.14A Downsampled I / Q data 1400a resulting from the downsampling is shown. Fig. 14B A phase (degrees) plot 1400b of downsampled I / Q data is shown. Fig. 14C A graph 1400c of the normalized amplitude of downsampled I / Q data is shown. In this particular illustrated example, the amplitude range is only 10% and the phase changes by approximately 1.5 degrees.

[0105] Example

[0106] Example 1: An operation method in an ultrasound system, the method comprising:

[0107] generating a drive signal having a nominal pulse repetition frequency;

[0108] introducing a variation from a nominal frequency into the drive signal, the variation being at least an order of magnitude less than the nominal pulse repetition frequency;

[0109] providing a drive signal having the introduced variation to at least one ultrasonic transducer so as to cause the at least one ultrasonic transducer to transmit an ultrasonic signal having the variation relative to a nominal pulse repetition frequency;

[0110] transmitting an ultrasonic signal via at least one ultrasonic transducer, the transmitted ultrasonic signal having a varying pulse repetition frequency, the varying pulse repetition frequency representing a variation relative to a nominal pulse repetition frequency; and

[0111] A return signal is received via the at least one ultrasonic transducer.

[0112] Example 2. The method of Example 1, wherein the variation introduced into the drive signal is in addition to any variation caused by clock jitter, if any, of a master oscillator.

[0113] Example 3. A method according to Example 2, wherein introducing a change into the drive signal includes introducing a defined pulse repetition frequency change into the drive signal.

[0114] Example 4. A method according to Example 3, wherein introducing a defined pulse repetition frequency variation into the drive signal includes introducing a defined pulse repetition frequency variation into the drive signal that changes in a defined pattern over time.

[0115] Example 5. A method according to Example 2, wherein introducing changes into the drive signal includes introducing random pulse repetition frequency changes into the drive signal.

[0116] Example 6. The method of Example 2, wherein introducing a change into the drive signal comprises introducing a delay into the drive signal via a delay circuit.

[0117] Example 7. A method according to Example 1, wherein a change relative to a nominal frequency is introduced into the drive signal, and the change is at least one order of magnitude smaller than the nominal frequency, including introducing a change relative to the nominal frequency into the drive signal, and the change is at least two orders of magnitude smaller than the nominal pulse repetition frequency.

[0118] Example 8. A method according to Example 1, wherein a change relative to a nominal frequency is introduced into the drive signal, and the change is at least one order of magnitude smaller than the nominal frequency, including introducing a change relative to the nominal frequency into the drive signal, and the change is at least three orders of magnitude smaller than the nominal pulse repetition frequency.

[0119] Example 9. A method according to Example 1, wherein a change relative to a nominal frequency is introduced into the drive signal, and the change is at least one order of magnitude smaller than the nominal frequency, including introducing a change relative to the nominal frequency into the drive signal, and the change is at least four orders of magnitude smaller than the nominal pulse repetition frequency.

[0120] Example 10. A method according to Example 1, wherein a change relative to a nominal frequency is introduced into the drive signal, and the change is at least one order of magnitude smaller than the nominal frequency, including introducing a change relative to the nominal frequency into the drive signal, and the change is at least five orders of magnitude smaller than the nominal pulse repetition frequency.

[0121] Example 11. A method according to Example 1, wherein a change relative to a nominal frequency is introduced into the drive signal, and the change is at least one order of magnitude smaller than the nominal frequency, including introducing a change relative to the nominal frequency into the drive signal, and the change is at least six orders of magnitude smaller than the nominal pulse repetition frequency.

[0122] Example 12. A method according to any one of Examples 1 to 11, wherein a change relative to a nominal frequency is introduced into the drive signal, and the change is at least one order of magnitude smaller than the nominal frequency, including introducing a change relative to a nominal pulse repetition frequency into the drive signal.

[0123] Example 13. A method according to any one of Examples 1 to 11, wherein introducing a change relative to a nominal frequency into the drive signal includes introducing a change relative to a nominal pulse repetition frequency into the drive signal over multiple pulses emitted during a Doppler operating mode during one or more Doppler frames of capturing ultrasound data.

[0124] Example 14. An ultrasound system, comprising:

[0125] at least one ultrasonic transducer;

[0126] A control system comprising at least one drive circuit, wherein the control system operates as follows:

[0127] generating a drive signal having a nominal pulse repetition frequency;

[0128] introducing a variation in frequency relative to a nominal frequency into the drive signal; and

[0129] The at least one ultrasonic transducer is caused to transmit an ultrasonic signal having a varied pulse repetition frequency, the varied pulse repetition frequency representing a variation from a nominal pulse repetition frequency.

[0130] Example 15. An ultrasound system according to Example 14, wherein the variation introduced into the drive signal is in addition to any variation caused by clock jitter of a master oscillator, if any.

[0131] Example 16. An ultrasound system according to Example 14, wherein, in order to introduce a pulse repetition frequency variation into the drive signal, the control system introduces a defined pulse repetition frequency variation into the drive signal.

[0132] Example 17. An ultrasound system according to Example 14, wherein, in order to introduce a defined pulse repetition frequency variation into the drive signal, the control system introduces a defined pulse repetition frequency variation into the drive signal that changes in a defined pattern over time.

[0133] Example 18. An ultrasound system according to Example 14, wherein, in order to introduce pulse repetition frequency variations into the drive signal, the control system introduces random pulse repetition frequency variations into the drive signal.

[0134] Example 19. An ultrasound system according to Example 14, wherein, in order to introduce the change into the drive signal, a delay circuit introduces a delay into the drive signal.

[0135] Example 20. An ultrasound system according to Example 14, wherein, in order to introduce a change in the drive signal relative to a nominal frequency, the change is at least one order of magnitude smaller than the nominal pulse repetition frequency, the control system introduces a change in the drive signal relative to the nominal frequency, the change is at least two orders of magnitude smaller than the nominal pulse repetition frequency.

[0136] Example 21. An ultrasound system according to Example 14, wherein, in order to introduce a change in the drive signal relative to a nominal frequency, the change is at least one order of magnitude smaller than the nominal pulse repetition frequency, the control system introduces a change in the drive signal relative to the nominal frequency, the change is at least three orders of magnitude smaller than the nominal pulse repetition frequency.

[0137] Example 22. An ultrasound system according to Example 14, wherein, in order to introduce a change in the drive signal relative to a nominal frequency, the change is at least one order of magnitude smaller than the nominal pulse repetition frequency, the control system introduces a change in the drive signal relative to the nominal frequency, the change is at least four orders of magnitude smaller than the nominal pulse repetition frequency.

[0138] Example 23. An ultrasound system according to Example 14, wherein, in order to introduce a change in the drive signal relative to a nominal frequency, the change is at least an order of magnitude smaller than the nominal pulse repetition frequency, the control system introduces a change in the drive signal relative to the nominal frequency, the change is at least five orders of magnitude smaller than the nominal pulse repetition frequency.

[0139] Example 24. An ultrasound system according to Example 14, wherein, in order to introduce a change in the drive signal relative to a nominal frequency, the change is at least an order of magnitude smaller than the nominal pulse repetition frequency, the control system introduces a change in the drive signal relative to the nominal frequency, the change is at least six orders of magnitude smaller than the nominal pulse repetition frequency.

[0140] Example 25. An ultrasound system according to Example 14, wherein the at least one ultrasound transducer is coupled to the control system to provide a signal to the control system, the signal representing a return signal received by the at least one ultrasound transducer, and the control system is capable of operating to detect flicker artifacts in the received return signal in a color Doppler operating mode, the flicker artifacts being caused by an interaction of an ultrasound signal having a varying pulse repetition frequency with at least a portion of a marker that is ultrasound reflective and has an irregular surface.

[0141] Example 26. According to an ultrasound system described in any of Examples 14 to 23, in order to introduce changes relative to the nominal frequency into the drive signal, the control system introduces changes relative to the nominal pulse repetition frequency into the drive signal.

[0142] Example 27. An ultrasound system according to any one of Examples 14 to 23, wherein, in order to introduce changes relative to the nominal frequency into the drive signal, the control system introduces changes relative to the nominal pulse repetition frequency into the drive signal over multiple pulses emitted during a Doppler operating mode during capture of a Doppler frame of ultrasound data.

[0143] Example 28. A method of using an ultrasound system, the method comprising:

[0144] directing an ultrasound signal toward a portion of body tissue containing the marker, the ultrasound signal being characterized by a nominal pulse repetition frequency and having an actual pulse repetition frequency that varies over time relative to the nominal pulse repetition frequency;

[0145] receiving a return signal from the portion of the body tissue via at least one ultrasound transducer;

[0146] In a color Doppler mode of operation of the ultrasound system, detecting resonance of at least a portion of the marker induced by the ultrasound signal in the received return signal as a scintillation artifact; and

[0147] The marker is located in the body tissue based at least in part on flicker artifacts in a color Doppler mode of operation.

[0148] Example 29. The method according to Example 28, further comprising:

[0149] An ultrasound signal is generated via at least one ultrasound transducer, the ultrasound signal having a nominal frequency over a period of time, the ultrasound signal also having a pulse repetition frequency variation relative to the nominal pulse repetition frequency, the frequency variation being at least one or more orders of magnitude less than the nominal pulse repetition frequency.

[0150] Example 30. The method according to Example 28, further comprising:

[0151] An ultrasound signal is generated via at least one ultrasound transducer, the ultrasound signal having a nominal pulse repetition frequency over a period of time, the ultrasound signal also having a pulse repetition frequency variation relative to the nominal pulse repetition frequency, the frequency variation being at least one or more orders of magnitude less than the nominal pulse repetition frequency.

[0152] Example 31. The method of Example 30, wherein generating an ultrasonic signal comprises:

[0153] generating a drive signal having a nominal pulse repetition frequency;

[0154] introducing a frequency variation into the drive signal; and

[0155] A drive signal with the introduced variation is provided to the at least one ultrasonic transducer to cause the at least one ultrasonic transducer to transmit an ultrasonic signal having a pulse repetition frequency variation relative to a nominal pulse repetition frequency.

[0156] Example 32. A method according to Example 31, wherein introducing a frequency variation into the drive signal comprises introducing a variation into the drive signal relative to a nominal pulse repetition frequency over a plurality of pulses transmitted during a Doppler operating mode during a Doppler frame capturing ultrasound data.

[0157] Example 33. A method according to any one of Examples 28 to 32, wherein directing an ultrasonic signal toward a portion of body tissue containing a marker comprises directing an ultrasonic signal emitted by the at least one ultrasonic transducer toward a portion of body tissue containing a marker, wherein the marker comprises a hydrogel and a plurality of ultrasonic reflective elements carried by the hydrogel.

[0158] Example 34. A method according to any one of Examples 28 to 32, wherein directing an ultrasound signal toward a portion of body tissue containing a marker includes directing an ultrasound signal toward a portion of body tissue containing the following marker, wherein the marker includes an at least partially cross-linked hydrogel and a plurality of hollow shells at least temporarily wrapped by the at least partially cross-linked hydrogel, each hollow shell having a corresponding outer wall forming a cavity, the outer wall having an irregular outer surface, and the cavity does not contain a perfluorocarbon.

[0159] Example 35. An operating method in an ultrasound system, the method comprising:

[0160] generating a drive signal via a master oscillator, the drive signal having a nominal pulse repetition frequency;

[0161] introducing a variation in the pulse repetition frequency of the drive signal relative to a nominal pulse repetition frequency; and

[0162] At least one ultrasound transducer is driven via a drive signal with an introduced variation of the pulse repetition frequency.

[0163] Example 36. A method according to Example 35, wherein introducing a pulse repetition frequency variation into the drive signal comprises introducing a defined pulse repetition frequency variation into the drive signal.

[0164] Example 37. A method according to Example 35, wherein introducing a defined pulse repetition frequency variation into the drive signal includes introducing a defined pulse repetition frequency variation into the drive signal that changes in a defined pattern over time.

[0165] Example 38. A method according to Example 35, wherein introducing pulse repetition frequency variations into the drive signal includes introducing random pulse repetition frequency variations into the drive signal.

[0166] Example 39. A method according to Example 35, wherein introducing a pulse repetition frequency variation into the drive signal comprises introducing a pulse repetition frequency variation that is at least two orders of magnitude less than a nominal pulse repetition frequency.

[0167] Example 40. A method according to Example 35, wherein introducing the pulse repetition frequency variation into the drive signal includes introducing the pulse repetition frequency variation via a gate generator of the ultrasound system.

[0168] Example 41. The method according to Example 35, further comprising:

[0169] An ultrasound signal emitted by the at least one ultrasound transducer is directed toward a portion of body tissue containing a marker comprising a hydrogel and a plurality of ultrasound reflective elements carried by the hydrogel.

[0170] Example 42. The method according to any one of Examples 35 to 41, further comprising:

[0171] Directing the ultrasonic signal emitted by the at least one ultrasonic transducer toward a portion of body tissue containing a marker includes directing the ultrasonic signal emitted by the at least one ultrasonic transducer toward a portion of body tissue containing a marker, wherein the marker includes a hydrogel and a plurality of ultrasonic reflective elements carried by the hydrogel.

[0172] Example 43. The method according to any one of Examples 35 to 41, further comprising:

[0173] An ultrasonic signal emitted by the at least one ultrasonic transducer is directed toward a portion of body tissue containing a marker, the marker comprising an at least partially cross-linked hydrogel and a plurality of hollow shells at least temporarily encapsulated by the at least partially cross-linked hydrogel, each hollow shell having a respective outer wall forming a cavity, the outer wall having an irregular outer surface, and the cavity being free of perfluorocarbon.

[0174] Example 44. A method according to any one of Examples 35 to 43, wherein introducing a change in the pulse repetition frequency of the drive signal relative to a nominal pulse repetition frequency includes introducing a change in the pulse repetition frequency on multiple pulses transmitted during a Doppler operating mode during one or more Doppler frames of ultrasound data being captured.

[0175] Example 45. A marker, comprising:

[0176] At least one hollow shell has at least one outer wall forming a cavity, the cavity being free of perfluorocarbon.

[0177] Example 46. A marker according to Example 45, wherein the cavity of the at least one hollow shell contains a gas.

[0178] Example 47. A marker according to Example 45, wherein the cavity of at least one hollow shell contains air.

[0179] Example 48. A marker according to Example 45, wherein the cavity of the at least one hollow shell contains an inert gas.

[0180] Example 49. A marker according to Example 45, wherein the at least one hollow shell comprises silicon dioxide.

[0181] Example 50. A marker according to Example 45, wherein the at least one hollow shell is composed of silicon dioxide.

[0182] Example 51. A marker according to Example 45, wherein the at least one hollow shell is porous.

[0183] Example 52. A marker according to Example 51, wherein the at least one hollow shell includes a hydrophobic coating that at least temporarily seals one or more pores thereof.

[0184] Example 53. A marker according to Example 45, wherein the at least one hollow shell includes a plurality of hollow shells.

[0185] Example 54. The marker according to Example 53, further comprising:

[0186] A hydrogel binds the plurality of hollow shells together.

[0187] Example 55. A marker according to Example 54, wherein the hydrogel is an at least partially cross-linked hydrogel.

[0188] Example 56. A marker according to any one of Examples 50 or 55, wherein the hydrogel is gelatin.

[0189] Example 57. A marker according to any one of Examples 45 to 55, wherein the hollow shell has a rough outer surface.

[0190] Example 58. A marker according to any one of Examples 45 to 55, wherein the hollow shell is highly reflective to ultrasound.

[0191] Example 59. According to the marker described in any one of Examples 45 to 55, the hollow shell has a rough outer surface and is highly reflective to ultrasound.

[0192] Example 60. A marker, comprising:

[0193] a hydrogel carrier; and

[0194] A plurality of ultrasound reflective elements are carried by the hydrogel carrier, wherein the ultrasound reflective elements have high ultrasound reflectivity and irregular outer surfaces and are solid particles or porous non-spherical particles.

[0195] Example 61. A marker according to Example 60, wherein the hydrogel carrier combines the multiple ultrasound reflective elements together.

[0196] Example 62. A marker according to Example 61, wherein the hydrogel carrier is an at least partially cross-linked hydrogel.

[0197] Example 63. A marker according to any one of Examples 61 or 62, wherein the hydrogel carrier comprises gelatin.

[0198] Example 64. A marker according to any one of Examples 61 or 62, wherein each of the plurality of ultrasound reflective elements comprises a corresponding hollow shell having at least one outer wall forming a cavity, and the cavity does not contain perfluorocarbon.

[0199] Example 65. A marker according to Example 60, wherein the cavity of the hollow shell contains a gas.

[0200] Example 66. A marker according to Example 60, wherein the cavity of the hollow shell contains air.

[0201] Example 67. A marker according to Example 60, wherein the cavity of the hollow shell contains an inert gas.

[0202] Example 68. A marker according to Example 60, wherein the hollow shell comprises silica.

[0203] Example 69. A marker according to Example 60, wherein the hollow shell is composed of silicon dioxide.

[0204] Example 70. A marker according to Example 60, wherein the hollow shell is porous.

[0205] Example 71. A marker according to Example 60, wherein each of the plurality of ultrasound reflective elements includes a corresponding hydrophobic coating that at least temporarily seals one or more holes thereof.

[0206] Example 72. A marker according to any one of Examples 60 to 62 or Examples 64 to 71, wherein the hollow shell has a rough outer surface.

[0207] Example 73. A marker according to any one of Examples 60 to 62 or Examples 64 to 71, wherein the hollow shell is highly reflective to ultrasound.

[0208] Example 74. A marker according to any one of Examples 60 to 62 or Examples 64 to 71, wherein the hollow shell has a rough outer surface and the hollow shell is highly reflective to ultrasound.

[0209] Example 75. A kit comprising:

[0210] at least one marker, the at least one marker comprising: a plurality of hollow shells having at least one outer wall forming a cavity, and a hydrogel bonding the plurality of hollow shells together; and

[0211] An ultrasound system comprising: at least one ultrasonic transducer and a control system, the control system comprising at least one drive circuit, the control system being operative to: generate a drive signal having a nominal pulse repetition frequency; introduce a variation into the drive signal relative to the nominal frequency; and cause the at least one ultrasonic transducer to transmit an ultrasound signal having a varied pulse repetition frequency, the varied pulse repetition frequency representing a variation relative to the nominal pulse repetition frequency.

[0212] Example 76. A kit according to Example 75, wherein, in order to introduce changes relative to the nominal frequency into the drive signal, the control system introduces changes relative to the nominal pulse repetition frequency into the drive signal over multiple pulses emitted during a Doppler operating mode during capture of a Doppler frame of ultrasound data.

[0213] Example 77. A kit according to Example 75, wherein the cavity of the hollow shell contains a gas.

[0214] Example 78. A kit according to Example 75, wherein the cavity of the hollow shell contains air and does not contain perfluorocarbons.

[0215] Example 79. A kit according to Example 75, wherein the hollow shell comprises silicon dioxide.

[0216] Example 80. A kit according to Example 75, wherein the hollow shell is composed of silicon dioxide.

[0217] Example 81. A kit according to Example 75, wherein the hollow shell is porous.

[0218] Example 82. A kit according to Example 76, wherein each of the hollow shells has a hydrophobic coating that at least temporarily seals one or more holes thereof.

[0219] Example 83. A kit according to Example 77, wherein the hydrogel is an at least partially cross-linked hydrogel.

[0220] Example 84. A kit according to any of Examples 82 or 83, wherein the hydrogel is gelatin.

[0221] Example 85. A kit according to any of Examples 75 to 83, wherein the hollow shell has a rough outer surface.

[0222] Example 86. A kit according to any of Examples 75 to 83, wherein the hollow shell is highly reflective to ultrasound.

[0223] Example 87. A kit according to any one of Examples 75 to 83, wherein the hollow shell has a rough outer surface and the hollow shell is highly reflective to ultrasound.

[0224] Example 88. A kit according to any of Examples 75 to 83, wherein, in order to introduce changes into the drive signal relative to a nominal frequency, the control system introduces changes into the drive signal relative to a change in a nominal pulse repetition frequency.

[0225] The foregoing detailed description has been described various embodiments of the device and / or process by using block diagrams, schematic diagrams, and examples. As long as such block diagrams, schematic diagrams, and examples contain one or more functions and / or operations, it will be understood by those skilled in the art that each function and / or operation in such block diagrams, schematic diagrams, or examples can be implemented individually and / or together by various hardware, software, firmware, or almost any combination thereof. In one embodiment, the subject matter can be implemented via an application-specific integrated circuit (ASIC). However, it will be appreciated by those skilled in the art that all or part of the embodiments disclosed herein can be implemented equivalently in a standard integrated circuit, as one or more computer programs running on one or more computers (e.g., as one or more programs running on one or more computer systems), as one or more programs running on one or more controllers (e.g., microcontrollers), as one or more programs running on one or more processors (e.g., microprocessors), as firmware, or as almost any combination thereof, and, according to the present invention, designing circuits and / or writing code for software and / or firmware will be completely within the skill of those of ordinary skill in the art.

[0226] Those skilled in the art will recognize that many of the methods or algorithms set forth herein may employ additional acts, may omit some acts, and / or may perform acts in an order different from that specified.

[0227] Furthermore, those skilled in the art will appreciate that the mechanisms taught herein can be distributed as a program product in a variety of forms, and that the illustrative embodiments apply equally, regardless of the specific type of signal-bearing medium used to actually perform the distribution. Examples of signal-bearing media include, but are not limited to, the following: recordable type media, such as floppy disks, hard drives, CD ROMs, digital tapes, and computer memory.

[0228] The various embodiments described above can be combined to provide further embodiments. 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 The present invention relates to the present invention in accordance with the present invention and to the invention of the present invention, and to the invention of the present invention. The present invention relates to the present invention in accordance with the present invention and to the invention of the present invention. The present invention relates to the present invention in accordance with the present invention. The present invention relates to the present invention in accordance with the present invention. The present invention relates to the present invention in accordance with the present invention. The present invention relates to the present invention in accordance with the present invention. The present invention relates to the present invention in accordance with the present invention.

[0229] These and other changes can be made to the embodiments of the specification according to the above detailed description. Generally, in the appended claims, the terms used should not be interpreted as limiting the claims to the specific embodiments disclosed in the specification and claims, but should be understood to include all possible embodiments and equivalents protected by the appended claims. Therefore, the claims are not limited by the disclosure.

Claims

1. An operating method in an ultrasound system, the method comprising: generating a drive signal having a nominal pulse repetition frequency; introducing a variation from a nominal pulse repetition frequency into the drive signal to intentionally introduce an artifact considered as undesirable noise, the variation being at least an order of magnitude smaller than the nominal pulse repetition frequency; providing a drive signal having the introduced variation to at least one ultrasonic transducer so as to cause the at least one ultrasonic transducer to transmit an ultrasonic signal having the variation relative to a nominal pulse repetition frequency; transmitting an ultrasonic signal via at least one ultrasonic transducer, the transmitted ultrasonic signal having a varying pulse repetition frequency, the varying pulse repetition frequency representing a variation relative to a nominal pulse repetition frequency; receiving a return signal via the at least one ultrasonic transducer; detecting resonance of at least a portion of the marker in the received return signal, the resonance caused by interaction of the varying interrogation signal with the ultrasound reflective element; and The marker is located based at least in part on the detected resonance.

2. The method according to claim 1, wherein: The variations introduced into the drive signal are in addition to any variations caused by clock jitter, if any, of the master oscillator.

3. The method according to claim 2, wherein: Introducing a variation into the drive signal comprises introducing a defined pulse repetition frequency variation into the drive signal.

4. The method according to claim 3, wherein: Introducing a defined pulse repetition frequency variation into the drive signal comprises introducing a defined pulse repetition frequency variation into the drive signal that changes in a defined pattern over time.

5. The method according to claim 2, wherein: Introducing variations into the drive signal includes introducing random pulse repetition frequency variations into the drive signal.

6. The method according to claim 2, wherein: Introducing a change into the drive signal includes introducing a phase change into the drive signal.

7. The method according to claim 1, wherein: Introducing a change in the drive signal relative to a nominal pulse repetition frequency, wherein the change is at least one order of magnitude less than the nominal pulse repetition frequency, includes introducing a change in the drive signal relative to the nominal pulse repetition frequency, wherein the change is at least two orders of magnitude less than the nominal pulse repetition frequency.

8. The method according to claim 1, wherein: Introducing a change in the drive signal relative to a nominal pulse repetition frequency, wherein the change is at least one order of magnitude less than the nominal pulse repetition frequency, includes introducing a change in the drive signal relative to the nominal pulse repetition frequency, wherein the change is at least three orders of magnitude less than the nominal pulse repetition frequency.

9. The method according to claim 1, wherein: Introducing a change in the drive signal relative to a nominal pulse repetition frequency, wherein the change is at least one order of magnitude less than the nominal pulse repetition frequency, includes introducing a change in the drive signal relative to the nominal pulse repetition frequency, wherein the change is at least four orders of magnitude less than the nominal pulse repetition frequency.

10. The method according to claim 1, wherein: Introducing a change in the drive signal relative to a nominal pulse repetition frequency, wherein the change is at least one order of magnitude less than the nominal pulse repetition frequency, includes introducing a change in the drive signal relative to the nominal pulse repetition frequency, wherein the change is at least five orders of magnitude less than the nominal pulse repetition frequency.

11. The method according to claim 1, wherein: Introducing a change in the drive signal relative to a nominal pulse repetition frequency, wherein the change is at least one order of magnitude less than the nominal pulse repetition frequency, includes introducing a change in the drive signal relative to the nominal pulse repetition frequency, wherein the change is at least six orders of magnitude less than the nominal pulse repetition frequency.

12. The method according to any one of claims 1 to 11, wherein: Introducing a variation in the drive signal relative to a nominal pulse repetition frequency, the variation being at least an order of magnitude less than the nominal pulse repetition frequency, comprising introducing the variation in the drive signal relative to the nominal pulse repetition frequency on at least one pulse transmitted during a Doppler operating mode during capture of a corresponding Doppler frame of ultrasound data.

13. The method according to any one of claims 1 to 11, wherein: Introducing a variation from a nominal pulse repetition frequency into the drive signal includes introducing a variation from a nominal pulse repetition frequency into the drive signal over a plurality of pulses transmitted during a Doppler mode of operation during capture of one or more Doppler frames of ultrasound data.

14. An ultrasound system comprising: at least one ultrasonic transducer; A control system comprising at least one drive circuit, wherein the control system operates as follows: generating a drive signal having a nominal pulse repetition frequency; introducing a variation to the drive signal relative to a nominal pulse repetition frequency to intentionally introduce an artifact considered to be undesirable noise, the variation being at least an order of magnitude smaller than the nominal pulse repetition frequency; causing the at least one ultrasonic transducer to transmit an ultrasonic signal having a varied pulse repetition frequency, the varied pulse repetition frequency representing a variation relative to a nominal pulse repetition frequency; detecting resonance of at least a portion of the marker in the received return signal, the resonance caused by interaction of the varying interrogation signal with the ultrasound reflective element; and The marker is located based at least in part on the detected resonance.

15. The ultrasound system of claim 14, wherein: The variations introduced into the drive signal are in addition to any variations caused by clock jitter, if any, of the master oscillator.

16. The ultrasound system of claim 14, wherein: In order to introduce a change relative to the nominal pulse repetition frequency into the drive signal, the control system introduces a defined change relative to the nominal pulse repetition frequency into the drive signal.

17. The ultrasound system of claim 14, wherein: In order to introduce a defined variation with respect to a nominal pulse repetition frequency into the drive signal, the control system introduces a defined variation with respect to a nominal pulse repetition frequency into the drive signal which varies in a defined pattern over time.

18. The ultrasound system of claim 14, wherein: In order to introduce variations in the drive signal relative to the nominal pulse repetition frequency, the control system introduces random variations in the drive signal relative to the nominal pulse repetition frequency.

19. The ultrasound system of claim 14, wherein: In order to introduce a variation in the drive signal relative to the nominal pulse repetition frequency, a delay circuit introduces a phase variation in the drive signal.

20. The ultrasound system of claim 14, wherein: In order to introduce a change in the drive signal relative to a nominal pulse repetition frequency, wherein the change is at least one order of magnitude smaller than the nominal pulse repetition frequency, the control system introduces a change in the drive signal relative to the nominal pulse repetition frequency, wherein the change is at least two orders of magnitude smaller than the nominal pulse repetition frequency.

21. The ultrasound system of claim 14, wherein: In order to introduce a change in the drive signal relative to a nominal pulse repetition frequency, wherein the change is at least one order of magnitude smaller than the nominal pulse repetition frequency, the control system introduces a change in the drive signal relative to the nominal pulse repetition frequency, wherein the change is at least three orders of magnitude smaller than the nominal pulse repetition frequency.

22. The ultrasound system of claim 14, wherein: In order to introduce a change in the drive signal relative to a nominal pulse repetition frequency, wherein the change is at least one order of magnitude smaller than the nominal pulse repetition frequency, the control system introduces a change in the drive signal relative to the nominal pulse repetition frequency, wherein the change is at least four orders of magnitude smaller than the nominal pulse repetition frequency.

23. The ultrasound system of claim 14, wherein: In order to introduce a change in the drive signal relative to a nominal pulse repetition frequency, wherein the change is at least one order of magnitude smaller than the nominal pulse repetition frequency, the control system introduces a change in the drive signal relative to the nominal pulse repetition frequency, wherein the change is at least five orders of magnitude smaller than the nominal pulse repetition frequency.

24. The ultrasound system of claim 14, wherein: In order to introduce a change in the drive signal relative to a nominal pulse repetition frequency, wherein the change is at least one order of magnitude smaller than the nominal pulse repetition frequency, the control system introduces a change in the drive signal relative to the nominal pulse repetition frequency, wherein the change is at least six orders of magnitude smaller than the nominal pulse repetition frequency.

25. The ultrasound system of claim 14, wherein: The at least one ultrasonic transducer is coupled to the control system to provide a signal to the control system, the signal being representative of a return signal received by the at least one ultrasonic transducer, and the control system is operable to detect flicker artifacts in the received return signal in a color Doppler operating mode, the flicker artifacts being caused by an interaction of an ultrasonic signal having a varying pulse repetition frequency with at least a portion of a marker that is ultrasonically reflective and has an irregular surface.

26. The ultrasound system of any one of claims 14 to 23, wherein: To introduce a variation in the drive signal relative to a nominal pulse repetition frequency, the control system introduces a variation in the drive signal relative to a variation in the nominal pulse repetition frequency.

27. An ultrasound system according to any one of claims 14 to 23, wherein: To introduce variations from a nominal pulse repetition frequency into the drive signal, the control system introduces variations from a nominal pulse repetition frequency into the drive signal over a plurality of pulses transmitted during a Doppler operating mode during capture of a Doppler frame of ultrasound data.

28. A method of using an ultrasound system, the method comprising: generating an ultrasound signal via at least one ultrasound transducer, the ultrasound signal having a nominal pulse repetition frequency over a period of time, the ultrasound signal also having a pulse repetition frequency variation relative to the nominal pulse repetition frequency, the pulse repetition frequency variation being at least one or more orders of magnitude less than the nominal pulse repetition frequency; directing an ultrasound signal toward a portion of body tissue containing a marker, the ultrasound signal being characterized by a nominal pulse repetition frequency and having an actual pulse repetition frequency that varies over time relative to the nominal pulse repetition frequency to intentionally introduce an artifact, the variation being at least an order of magnitude less than the nominal pulse repetition frequency; receiving a return signal from the portion of the body tissue via at least one ultrasound transducer; In a color Doppler mode of operation of the ultrasound system, detecting a resonance of at least a portion of the marker as a scintillation artifact in a received return signal, the resonance caused by an interaction of a varying interrogation signal with an ultrasound reflective element; and The marker is located in the body tissue based at least in part on flicker artifacts in a color Doppler mode of operation.

29. The method according to claim 28, wherein: Generating an ultrasonic signal includes: generating a drive signal having a nominal pulse repetition frequency; introducing a frequency variation into the drive signal; and A drive signal with the introduced variation is provided to the at least one ultrasonic transducer to cause the at least one ultrasonic transducer to transmit an ultrasonic signal having a pulse repetition frequency variation relative to a nominal pulse repetition frequency.

30. The method of claim 29, wherein: Introducing frequency variation into the drive signal includes introducing variation into the drive signal relative to a nominal pulse repetition frequency over a plurality of pulses transmitted during a Doppler mode of operation during capture of a Doppler frame of ultrasound data.

31. The method according to any one of claims 28 to 30, wherein: Directing an ultrasound signal toward a portion of body tissue containing a marker includes directing an ultrasound signal emitted by the at least one ultrasound transducer toward the portion of body tissue containing a marker, the marker comprising a hydrogel and a plurality of ultrasound reflective elements carried by the hydrogel.

32. The method according to any one of claims 28 to 30, wherein: Directing an ultrasound signal toward a portion of body tissue containing a marker includes directing an ultrasound signal toward a portion of body tissue containing a marker comprising an at least partially cross-linked hydrogel and a plurality of hollow shells at least temporarily encapsulated by the at least partially cross-linked hydrogel, each hollow shell having a respective outer wall forming a cavity, the outer wall having an irregular outer surface, and the cavity being free of perfluorocarbon.

33. A method of operation in an ultrasound system, the method comprising: generating a drive signal via a master oscillator, the drive signal having a nominal pulse repetition frequency; introducing a variation in the pulse repetition frequency of the drive signal relative to a nominal pulse repetition frequency to intentionally introduce an artifact considered as undesirable noise, the variation being at least an order of magnitude less than the nominal pulse repetition frequency; driving at least one ultrasonic transducer via a drive signal having an introduced variation of a pulse repetition frequency; as well as A resonance of at least a portion of the marker in the received return signal is detected, the resonance caused by the interaction of the varying interrogation signal with the ultrasound reflecting element.

34. The method of claim 33, wherein: Introducing a pulse repetition frequency variation into the drive signal comprises introducing a defined pulse repetition frequency variation into said drive signal.

35. The method of claim 33, wherein: Introducing a defined pulse repetition frequency variation into the drive signal comprises introducing a defined pulse repetition frequency variation into the drive signal that changes in a defined pattern over time.

36. The method of claim 33, wherein: Introducing pulse repetition frequency variations into the drive signal comprises introducing random pulse repetition frequency variations into the drive signal.

37. The method of claim 33, wherein: Introducing the pulse repetition frequency variation into the drive signal includes introducing a pulse repetition frequency variation that is at least two orders of magnitude less than a nominal pulse repetition frequency.

38. The method of claim 33, wherein: Introducing the pulse repetition frequency variation into the drive signal includes introducing the pulse repetition frequency variation via a gate generator of the ultrasound system.

39. The method of claim 33, further comprising: An ultrasound signal emitted by the at least one ultrasound transducer is directed toward a portion of body tissue containing a marker comprising a hydrogel and a plurality of ultrasound reflective elements carried by the hydrogel.

40. The method according to any one of claims 33 to 39, further comprising: Directing the ultrasonic signal emitted by the at least one ultrasonic transducer toward a portion of body tissue containing a marker includes directing the ultrasonic signal emitted by the at least one ultrasonic transducer toward a portion of body tissue containing a marker, wherein the marker includes a hydrogel and a plurality of ultrasonic reflective elements carried by the hydrogel.

41. The method according to any one of claims 33 to 39, further comprising: An ultrasonic signal emitted by the at least one ultrasonic transducer is directed toward a portion of body tissue containing a marker, the marker comprising an at least partially cross-linked hydrogel and a plurality of hollow shells at least temporarily encapsulated by the at least partially cross-linked hydrogel, each hollow shell having a respective outer wall forming a cavity, the outer wall having an irregular outer surface, and the cavity being free of perfluorocarbon.

42. The method according to any one of claims 33 to 39, wherein: Introducing a variation in the pulse repetition frequency of the drive signal relative to a nominal pulse repetition frequency includes introducing a variation in the pulse repetition frequency across a plurality of pulses transmitted during the Doppler mode of operation during the capture of one or more Doppler frames of ultrasound data.

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