Systems and methods for detecting magnetic markers for surgical guidance

Abstract

Systems and methods of detecting magnetic markers for surgical guidance. Methods and systems of detecting magnetic markers to guide a surgeon to a region of interest during a surgical procedure include generating a driving magnetic field having a cyclic pattern comprising two or more consecutive time periods, the driving magnetic field having a substantially constant non-zero amplitude during each of the consecutive time periods, and the amplitude of the driving magnetic field during at least one of the time periods being different than the amplitude of the driving magnetic field during at least one other of the time periods; detecting a response magnetic field; selecting at least one signal from the sensed plurality of signals, wherein each signal corresponds to the response magnetic field detected during a respective one of the consecutive time periods of each cycle; using the selected at least one signal to determine a detection signal corresponding to the magnetic marker; and generating an output signal (e.g., an audio or display signal) based on the strength of the detection signal.

Description

TECHNICAL FIELD

[0001] The present disclosure relates generally to the field of surgical guidance; more specifically, to systems and methods for detecting markers and tracers of an internal site (e.g., a lesion to be surgically removed) for assisted localization. BACKGROUND

[0002] Markers are used to guide surgeons to areas of interest during surgical procedures, where the site of interest is physically invisible or inaccessible; for example, a small tumor that needs to be removed. Markers can be placed in the body at the site of interest during a biopsy or other surgical procedure; for example, a cancerous lesion. Ideally, such markers are deployable through a narrow gauge needle. The markers are placed under imaging guidance, such as ultrasound or X-ray / mammography. During the subsequent procedure, the markers are detected and localized using a hand-held probe that provides auditory, visual, or other feedback to the surgeon to guide the procedure. The markers are typically removed along with the surrounding tissue.

[0003] Markers can also be used to mark lymph nodes prior to a course of neoadjuvant therapy. In this way, even if fibrosis from the neoadjuvant therapy has affected the lymphatic vessels such that conventional lymphatic tracers are unable to flow to the draining lymph nodes, the nodes can be readily identified for removal after the therapy.

[0004] One such tumor marking method is to use a marker containing a radioisotope, such as iodine 90, that can be detected using a hand-held gamma detection probe; for example, a Geiger counter. However, the use of radioactive materials is heavily regulated, making it challenging to establish a radioactive seed program at all but the largest academic hospital centers.

[0005] A different approach, discussed in WO 2011 / 067576, WO 2014 / 013235, and WO 2014 / 140567 (the contents of which are incorporated herein by reference), uses magnetic fields and magnetic markers with high magnetic susceptibility. A hand-held probe generates an alternating field that excites the magnetically responsive markers and detects the response magnetic field.

[0006] Liquid or liquid-borne markers can also be used in surgical procedures; for example, in the detection of sentinel lymph nodes for biopsy. Such markers can be referred to as "tracers". Sentinel lymph node biopsy is an important technique used in staging certain tumours; that is, assessing the spread of certain types of cancer; particularly breast cancer. A tracer can be injected near a cancerous tumour. The tracer particles are then taken up in the lymphatic system and flow to draining lymph nodes, where they accumulate. These nodes can then be located by visual discoloration of the nodes or using a hand-held probe, so that they can be excised for pathological assessment. Nodes identified in this way are referred to as "sentinel" nodes, because they are the nodes to which cancer can spread. The surgical procedure for identifying and removing these nodes is referred to as a sentinel lymph node biopsy procedure.

[0007] Typically, both procedures (tumour excision and lymph node excision) occur in the same surgery. Thus, both tracer and marker can be present in the breast or other tissue at the same time.

[0008] As mentioned above, one approach is to use a liquid marker containing a radioisotope; for example, technetium-99m sulphur colloid. The radio-labelled colloid particles accumulate in the draining lymph nodes, which can then be identified for excision using a hand-held gamma probe (Geiger counter). However, technetium-99m has a half-life of only 6 hours, so it must be injected close to the time of surgery, creating a planning challenge. It can also have a complex supply chain and can not be available to isolated hospitals. There can also be supply interruptions if the reactor producing the isotope is not working at a given time.

[0009] A different approach is to use a suspension of superparamagnetic iron oxide nanoparticles. These particles have no half-life, meaning that they are available at any hospital and can be injected days before surgery, making planning more convenient.

[0010] The nanoparticles can be detected by a magnetic probe, for example, the hand-held probe mentioned above. However, such a probe can respond to both magnetic markers and iron oxide nanoparticle suspensions at that time. In particular, a portion of the nanoparticle suspension can remain in the region of the injection site near the lesion. It is desirable to perform both lesion removal surgery and sentinel lymph node biopsy in a single surgery, but it has proven problematic to provide a detection system that can distinguish between lesion markers and other magnetically responsive materials. This is exemplified in the accompanying drawings. Figure 1A

[0011] ​Other magnetically responsive materials include surgical tools made of metal. It is desirable to develop magnetic markers or tracers that can be detected even in the presence of metal tools. This is illustrated in Figure 1B . .

[0012] The human body itself has a magnetic response that can interfere with the detection of magnetic markers, because water, which is the main component of human tissue, can produce a diamagnetic response. Typically, during a localization procedure, a large amount of human tissue surrounds the injected marker. Therefore, it would be advantageous to have a marker that can be accurately localized against the background signal from the human body. This is illustrated in Figure 1C . .

[0013] Multiple markers can be present at the site of a lesion. For example, a biopsy marker can have been placed beforehand to monitor the evolution of a tumor mass over time by mammography or ultrasound scanning. It is desirable that a probe adapted to perform lesion localization during surgery should be sensitive only to the marker placed for this purpose. This is illustrated in Figure 1D . .

[0014] If magnetic markers are used to mark special lymph nodes and magnetic tracers are also used to map and identify other sentinel lymph nodes, there can be one or more lymph nodes in which both a magnetic marker and a magnetic tracer are present. It would be advantageous to be able to locate and identify which lymph nodes are marked and which only contain tracers. It can also be advantageous to be able to quantify the amount of tracer in a node even in the presence of a marker. Therefore, there is a need to discriminate between markers and tracers within a lymph node. This is illustrated in Figure 1E . .

[0015] One solution proposed for the above problems is to use markers that respond non-linearly to an excitation magnetic field. The full harmonic response can be analyzed to discriminate the markers from tracers, metal tools, the body, or other markers that have different and usually more linear responses at the same field strength.

[0016] Materials having a large Barkhausen discontinuity in the magnetization curve, i.e. "large Barkhausen jump" (LBJ) materials, undergo a rapid reversal of the magnetic polarization of the material when excited by an external magnetic field, also called switching field, whose field strength opposite to the instantaneous magnetic polarization of the wire exceeds a predetermined threshold. The markers thus exhibit a bistable behavior that reverses between two magnetic polarization states. The various magnetization reversals generate magnetic pulses with harmonic components. The distribution and the number of harmonics (more than tens of harmonics) can be measured to identify the markers from other materials.

[0017] For detection purposes, it is desirable to use a high external magnetic field that can excite the magnetic markers at a sufficiently long distance and, in particular, contribute to the above-mentioned bistable behavior. However, secondary magnetic sources that can be background magnetic sources can also exhibit non-linearities at high magnetic fields. For example, iron oxide nanoparticles that are used as magnetic tracers can typically be linear, but can exhibit some non-linearity at high magnetic fields. This can be particularly problematic when secondary magnetic sources are distributed over a large area. Parts of the secondary magnetic sources can be closer to the probe than the magnetic markers and can therefore experience a correspondingly high magnetic field and can in particular exhibit problematic high-field non-linearities. Since the user is not aware of the distribution or magnetic properties of the secondary magnetic sources, it is difficult to compensate for these secondary signals and to identify the desired markers.

[0018] Typically, existing solutions focus on exploiting only small drive magnetic fields. It has been shown (see, e.g., CA3031282A1) that some LBJ materials can exhibit a strong non-linear response even if the markers are shorter than the critical length and / or are excited below the switching field. Markers formed from such materials are referred to as sub-bistable markers. Other markers with lower levels or different types of non-linearity in their magnetic response can also be considered for discrimination against more linear secondary signals. For example, the non-linearity can be a result of non-linear electronic components included in the marker; for example, diodes.

[0019] Ideally, the excitation magnetic field (drive field) generated by the magnetic probe should include only one frequency component at the base frequency. It is also desirable to have a strong magnetic field to achieve a suitably large detection distance. However, it is challenging to generate an alternating magnetic field with a high field strength and a pure single frequency sinusoidal waveform at the desired frequency around the probe. When driving the amplifier with sufficient power to generate a strong field, some distortion or impurities are typically introduced in the sinusoidal waveform, which results in harmonics of the drive frequency.

[0020] Low-distortion operational amplifiers can provide a harmonic distortion of about -120 dB, where the harmonic distortion is the ratio of the rms (root mean square) value of the harmonic of interest (second harmonic, third harmonic, etc.) to the rms signal level. However, such low distortion can only be achieved at currents in the order of tenths of milliampere, which are typically too low. Typically, such amplifiers also use a resistive load, whereas magnetic probes typically use an inductive load. Furthermore, the harmonic distortion of operational amplifiers is typically measured by looking at the voltage, not the current. However, in the case of detecting magnetic markers of the kind described herein, the relevant harmonic distortion occurs in the excitation magnetic field that is generated by the current, not the voltage. Therefore, it is not straightforward to generate a high-purity drive field with off-the-shelf electronic components.

[0021] The typical optimised harmonic distortion of the drive field in a magnetic probe such as those in WO 2011 / 067576, WO 2014 / 013235 or WO 2014 / 140567 can be in the range -70dB to -100dB at the frequency of interest. This indicates that the harmonic components are less than 10,000 to 100,000 times smaller than the drive signal, which is acceptable for most applications relying on linear detection, even for high-end audio systems. However, in order to detect magnetic markers of the kind described, this level of harmonic distortion in the drive signal can easily be as large as the signal from a non-linear marker at a distance of some distance from the probe when reflected by a linear magnetic material close to the probe.

[0022] There is therefore a need to provide a system for detecting magnetic markers or tracers in a human or animal body for surgical guidance which is able to distinguish non-linear markers from other magnetically responsive materials even with a non-pure drive field. The present disclosure aims to address this need.

[0023] US 5793289 discloses a kind of harmonic electronic article surveillance (EAS) system used in a different field to the present disclosure; i.e. detecting the presence of markers in an interrogation zone to prevent or deter theft of goods from a retail establishment. Markers comprising a magnetic element generate a detectable marker signal in the form of a perturbation of an alternating interrogation signal field radiated within the interrogation zone. The marker signal comprises a harmonic signal component which is a harmonic of the operating frequency of the interrogation signal. The interrogation signal is in the form of discrete pulses which allow the effective frequency of the interrogation signal to be increased without exceeding the prescribed limits on average radiated power. The detection circuitry can be arranged such that it does not detect the marker signal at times corresponding to the discrete pulses, thereby reducing the likelihood of false alarms in response to pulse noise. The timing of the pulses can be adjusted so that the pulses do not coincide with a periodic cyclic noise signal. Furthermore, when a signal is detected which is similar in shape to the marker signal but has an amplitude which exceeds a predetermined threshold level, the amplitude of the interrogation signal pulses can be reduced so that signals generated by markers can be distinguished from signals generated by objects such as shopping trolleys which can be inclined to generate signals which mimic the marker signal in response to a high level interrogation signal.

[0024] However, the EAS system of US 5793289, which starts from detecting the presence of markers in a relatively large interrogation zone such as in a retail store, is not suitable for detecting magnetic markers or tracers in a body for surgical guidance. The generation of a pulsed interrogation signal with substantially no amplitude between the discrete pulses would cause unwanted thermal effects within the signal generator which lead to inaccuracies, on which the detection of markers in a body relies, on the accurate detection of small changes in magnetic field. SUMMARY

[0025] According to one aspect of the disclosure, there is provided a method of detecting a magnetic marker to guide a surgeon to a region of interest during a surgical procedure, the method comprising the steps of: generating a drive magnetic field having a repeating pattern of two or more consecutive time periods, the drive magnetic field having a substantially constant non-zero amplitude during each of the consecutive time periods, and the amplitude of the drive magnetic field during at least one of the time periods being different to the amplitude of the drive magnetic field during at least one other of the time periods; detecting a response magnetic field; selecting at least one signal from a plurality of sensed signals, wherein each signal corresponds to the response magnetic field detected during a respective one of the consecutive time periods of each cycle; determining a detection signal corresponding to the magnetic marker using the selected at least one signal; and generating an output signal based on the strength of the detection signal.

[0026] In another aspect, the disclosure includes a magnetic detection system of detecting a magnetic marker to guide a surgeon to a region of interest during a surgical procedure, the magnetic detection system comprising: a drive unit configured to generate a drive magnetic field having a repeating pattern of two or more consecutive time periods, wherein the drive magnetic field has a substantially constant non-zero amplitude during each of the consecutive time periods, and the amplitude of the drive magnetic field during at least one of the time periods is different to the amplitude of the drive magnetic field during at least one other of the time periods; a magnetic field sensor configured to detect a response magnetic field; a processor configured to, based on the response magnetic field, select at least one signal from a plurality of sensed signals, wherein each signal corresponds to the response magnetic field detected during a respective one of the consecutive time periods of each cycle; determine a detection signal corresponding to the magnetic marker using the selected at least one signal; and generate an output signal based on the strength of the detection signal.

[0027] In some embodiments, the output signal can be used to control the operation of a user interface device (for example, such as a sound generator (e.g. a loudspeaker), a haptic device and / or a display) for outputting the output signal in a form perceptible to a user. Thus, in some embodiments, the output signal can comprise an audio signal, a haptic signal and / or a display signal. In some embodiments, the output signal can comprise a user feedback signal based on the marker proximity value, for example as disclosed in co-pending international application no. PCT / GB2021 / 051750, the contents of which are incorporated herein by reference. Thus, the marker proximity value can be determined based on the detection signal. In this sense, it will be understood that the output signal represents the output of the method or system of the invention, which conveys information relating to the detection of the magnetic marker; this does not refer to the drive magnetic field output by the drive unit.

[0028] It should be understood that references herein to a substantially constant non-zero amplitude or "different" amplitude of the drive magnetic field refer to the amplitude of the drive magnetic field at a substantially constant distance from the source of the drive magnetic field. Equivalently, a drive magnetic field having a substantially constant amplitude can be considered to be generated using a drive signal having a substantially constant amplitude as disclosed herein.

[0029] Typically, the amplitude of the drive magnetic field during at least one of the consecutive time periods is high relative to the amplitude of the drive magnetic field during at least one other of the consecutive time periods, the amplitudes being calculated to induce a non-linear response in the magnetic marker. The amplitude of the drive magnetic field during at least one of the consecutive time periods can be relatively low compared to the amplitude of the drive magnetic field during at least one of the consecutive time periods, the amplitudes being calculated to induce a substantially linear response in a tracer that can be present in the vicinity of the marker or any other magnetic material formed from a non-LBJ material. It should be understood that the drive unit can be configured such that the strength of the drive magnetic field is adjusted for use with one or more particular magnetic markers or tracers. A typical magnetic marker can include less than about 5 mg of LBJ material. Accordingly, in some embodiments, the drive unit can include a probe configured to generate a drive magnetic field having a maximum field strength of between 100 μΤ and about 2000 μΤ within about 5 mm of the probe during at least one of the consecutive time periods.

[0030] The drive magnetic field in at least one of the consecutive time periods can have an amplitude that is less than the maximum field strength. For example, in some embodiments, the drive magnetic field in at least one of the consecutive time periods can have an amplitude that is between about 10% and 90% of the maximum amplitude corresponding to the maximum field strength of the drive magnetic field. In some embodiments, the drive magnetic field in at least one of the consecutive time periods can have an amplitude that is between about 25% and 75% of the maximum amplitude of the drive magnetic field. Typically, the amplitude of the drive magnetic field in at least one of the consecutive time periods can be between about 25% and 50%, e.g., about 33%, of the maximum amplitude of the drive magnetic field. In the case where the cycle pattern of the drive magnetic field includes more than two consecutive time periods, the drive magnetic field can have different field strengths in two or more respective time periods that are a fraction of the maximum field strength within the ranges described above.

[0031] Accordingly, the method of the present disclosure includes detecting a response magnetic field during each of the consecutive time periods of the cyclic pattern to generate the plurality of sensed signals corresponding to the respective consecutive time periods. At least one of the sensed signals is then selected for a detection signal corresponding to the magnetic marker, and an output signal is generated based on the strength of the detection signal. Accordingly, the method of the present disclosure can involve analyzing the plurality of sensed signals from the consecutive time periods of the cyclic pattern as disclosed herein to determine a suitable detection signal.

[0032] Preferably, the two or more consecutive time periods forming the cyclic pattern can be contiguous, such that during performance of the method of the present disclosure, the consecutive time periods are uninterrupted and the amplitude of the driving magnetic field is never zero. However, in some embodiments, one or more short gaps of no or little field can be allowed between consecutive time periods of the driving field. Accordingly, in some embodiments, two or more of the consecutive time periods forming the cyclic pattern can be non-contiguous and have one or more short intervals between consecutive time periods in which the amplitude of the driving magnetic field is zero or near zero. However, such intervals should be minimized for the reasons discussed herein, and may, for example, cumulatively comprise less than about 25% of the total duration of the cyclic pattern, preferably less than 10%, more preferably less than 5%, and most preferably less than about 1%.

[0033] According to the method and system of the present disclosure, the response magnetic field is continuously detected across substantially the entire repeating pattern of consecutive time periods during which the amplitude of the driving magnetic field changes from one time period to another according to the pattern, and each consecutive time period results in a different respective sensed signal that depends on the amplitude of the driving magnetic field during that time period and the presence of the marker, tracer, and / or other secondary source of magnetic material. The method and system of the present disclosure includes selecting one or more of the sensed signals, and using the one or more selected signals to determine a detection signal corresponding to the marker. Thereafter, an output signal is generated based on the strength of the detection signal.

[0034] The duration of the consecutive time periods within each cycle can be substantially the same as or different from one another. The driving magnetic field can conveniently include a substantially constant frequency during all of the consecutive time periods.

[0035] In some embodiments, the cyclic pattern can include two consecutive time periods. The response magnetic field detected during each of the consecutive time periods can include a first response component at a first frequency and a second response component at a second frequency different from the first frequency.

[0036] According to another aspect of the present disclosure, there is thus provided a method of detecting a magnetic marker to guide a surgeon to a region of interest during a surgical procedure, the method comprising the steps of: generating a driving magnetic field comprising a first frequency, the driving magnetic field having a first amplitude for a first time period and a second amplitude for a second time period, the second amplitude being lower than the first amplitude; detecting a response magnetic field, the response magnetic field comprising a first response component at the first frequency and a second response component at a second frequency, the second frequency being different from the first frequency; selecting at least one signal from a first sensed signal and a second sensed signal, the first sensed signal corresponding to the response magnetic field detected during the first time period, the second sensed signal corresponding to the response magnetic field detected during the second time period; determining a detection signal corresponding to the magnetic marker using the selected at least one signal; and generating an output signal based on an intensity of the detection signal.

[0037] Suitably, the selecting step, the determining step and the generating step can be performed by a processor.

[0038] According to the present disclosure, it will be appreciated that the first time period and the second time period are different from each other in the sense that they are not simultaneous. Suitably, the first time period and the second time period are consecutive to each other; preferably without any interruption between them. This way, the amplitude of the driving magnetic field is never zero during the operation of the method. The first amplitude and the second amplitude are advantageously both non-zero, which helps to minimize unwanted thermal effects and potential inaccuracies, as described herein.

[0039] Accordingly, the step of generating the driving magnetic field can comprise alternating between the first amplitude and the second amplitude.

[0040] In some embodiments, the step of selecting the at least one signal can be based on identifying the presence of a secondary magnetic source, for example, a liquid magnetic tracer.

[0041] The step of identifying the presence of a secondary magnetic source can comprise calculating a harmonic ratio between the first response component at the first frequency and the second response component at the second frequency. Suitably, a first harmonic ratio based on one of the sensed signals (e.g., the first sensed signal) can be compared to a second harmonic ratio based on another one of the sensed signals (e.g., the second sensed signal).

[0042] In some embodiments, the step of identifying the presence of a secondary magnetic source can be based on comparing a spectral analysis of the response magnetic field to pre-recorded responses from an isolated magnetic marker and an isolated secondary source.

[0043] In some embodiments, the step of selecting the at least one signal can be based on an absolute magnitude of at least one of the plurality of sensed signals, e.g. the first sensed signal and / or the second sensed signal; e.g. whether the absolute magnitude of one or more of the sensed signals exceeds a predetermined threshold.

[0044] In yet another aspect, the disclosure includes a magnetic detection system for detecting a magnetic marker to guide a surgeon to a region of interest during a surgical procedure, the magnetic detection system comprising: a drive unit configured to generate a drive magnetic field comprising a first frequency, the drive magnetic field having a first amplitude for a first time period and a second amplitude for a second time period, the second amplitude being lower than the first amplitude; a magnetic field sensor configured to detect a response magnetic field, the response magnetic field comprising a first response component at the first frequency and a second response component at a second frequency, the second frequency being different from the first frequency; a processor configured to select at least one signal from a first sensed signal and a second sensed signal based on the response magnetic field, the first sensed signal corresponding to the response magnetic field detected during the first time period, the second sensed signal corresponding to the response magnetic field detected during the second time period; determine a detection signal corresponding to the magnetic marker using the selected at least one signal; and generate an output signal based on an intensity of the detection signal.

[0045] Other features of the disclosure are described below and / or claimed in the claims. BRIEF DESCRIPTION OF DRAWINGS

[0046] For a better understanding of the present disclosure and to show how the same can be carried into effect, there will now be described, by way of example only, with reference to the accompanying drawings in which:

[0047] Figures 1A to 1E is an exemplary diagram representing a use scenario of an embodiment;

[0048] Figure 2 is a schematic diagram of a magnetic detection system according to an embodiment of the disclosure;

[0049] Figure 3 is a schematic diagram of a magnetic detection system according to an embodiment of the disclosure;

[0050] Figure 4 shows an exemplary drive signal according to the disclosure;

[0051] Figure 5A is a graph showing a magnetization curve of an exemplary marker;

[0052] Figure 5B is a graph showing a magnetic response in the time domain;

[0053] Figure 5C is a graph showing the magnetic response in the frequency domain;

[0054] Figure 6A is a graph showing the magnetization curve of an exemplary tracer;

[0055] Figure 6B is a graph showing the magnetic response in the time domain;

[0056] Figure 6C is a graph showing the magnetic response in the frequency domain; and

[0057] Figure 7 is a schematic view of a magnetic detection system according to an embodiment. DETAILED DESCRIPTION

[0058] The present disclosure relates to a detection system and method for characterizing markers, more particularly magnetic markers, which can be implanted in the body for marking a target site, and to the detection and localization of implanted markers using a handheld probe.

[0059] The marker can be implanted at a site in the body where marking is required. This can be, for example, a tumor or other lesion or a site of interest in soft tissue. Examples include, but are not limited to, benign lesions, cancerous lesions, and lymph nodes. The marker can be placed in or near a lesion, or multiple markers can be placed to mark the edge or perimeter of a surgical site; for example, the edge of a tumor or soft tissue sarcoma.

[0060] In the drawings Figure 2 A schematic view of an embodiment of a detection system and marker according to the present disclosure is shown. The detection system 1 comprises a probe 10 which is connected to a base unit 4. The probe 10 has one or more drive coils which generate an alternating magnetic field to excite a magnetic marker 6. A magnetic tracer 7 can also be present in the vicinity or proximity of the marker 6.

[0061] The marker 6 comprises at least one piece of magnetically responsive material and can have a nonlinear magnetic susceptibility. The magnetization of the material can respond to an external magnetic field in a nonlinear manner. The material can have a large Barkhausen discontinuity in its magnetization curve and can be referred to as a "large Barkhausen jump material", "LBJ material", "bistable switching material" or "material with a large nonlinearity in its magnetization curve". For example, when a length of LBJ material is exposed to such an external magnetic field (switching field HSW), the magnetic polarization of the LBJ material undergoes a rapid reversal: the field strength of the external magnetic field which is opposite to the instantaneous magnetic polarization of the length of material exceeds a predetermined threshold value. This magnetization reversal produces a magnetic pulse with intense harmonic components.

[0062] The tracer 7 typically comprises a liquid containing a plurality of magnetic nanoparticles. For example, the tracer 7 can comprise a plurality of iron oxide nanoparticles. The tracer 7 is an example of a secondary magnetic source. In some cases, the tracer 7 can be considered to be a background magnetic source. The nanoparticles can be described as superparamagnetic nanoparticles. When the tracer 7 is exposed to an external field, the magnetic response can be substantially linear; that is, the magnetisation of the tracer 7 is proportional to the applied field. The magnetic response of the tracer 7 can be substantially linear when the strength of the external field is within a certain range. When the strength of the external magnetic field is greater than a certain linear threshold, the magnetisation of the tracer 7 can saturate, resulting in a non-linear magnetic response.

[0063] The probe 10 of the detection system further comprises one or more sense coils arranged to detect changes in the magnetic field caused by changes in the magnetisation of the marker 6 and / or the tracer 7.

[0064] In order to detect the marker 6 in a typical lesion or site of interest, the probe 10 desirably should have a detection depth of at least 30 mm, preferably greater than 40 mm, and more preferably greater than 50 mm. Ideally, the marker 6 gives the same response amplitude regardless of the direction of approach to the marker 6, i.e. it should have low magnestisation anisotropy. This is in order to provide consistent feedback to the surgeon about the position of the marker 6 relative to the probe 10.

[0065] Figure 3 An example probe 10 is illustrated in more detail. The detection probe 10 comprises a drive coil 102 for generating a drive magnetic field, and a sense coil 104 for detecting a response magnetic field.

[0066] The drive coil 102 is configured to generate a drive magnetic field by means of an applied current comprising a drive signal. The drive magnetic field is an alternating magnetic field generated to alternate at a fundamental frequency component fi. The drive coil 102 can be suitably configured to generate the drive magnetic field at one or more different output amplitudes.

[0067] The base unit 4 and the probe 10 can further comprise a sine wave generator and amplifier 100, and a harmonic filter and drive circuit 101 configured to generate the drive signal at the fundamental frequency fi. The sine wave generator and amplifier 100 is configured to generate and amplify an alternating current drive signal configured to alternate at the fundamental frequency fi. The amplifier 100 is configured to amplify the drive signal to one or more different amplitude levels. The amplifier 100 can be configured to amplify the drive signal to one of at least two distinct amplitude levels at a given time. For example, the two distinct amplitude levels can be referred to as A LOW and A HIGH where AHIGH greater than A LOW . Advantageously, as described herein, the drive signal can oscillate without interruption between A LOW and A HIGH . Thus, both A HIGH and A LOW may be non-zero. A HIGH may suitably have a substantially constant amplitude. A LOW may have a substantially constant amplitude. In some embodiments, the drive signal can have a continuous fundamental frequency f1.

[0068] As an illustration, Figure 4 an example of a suitable uninterrupted drive signal is illustrated. Figure 4 The drive signal of A LOW includes a cyclic pattern of two consecutive periods during each of which the drive signal has a substantially constant non-zero amplitude. The amplitude A HIGH of the drive signal during one of the periods is different from the amplitude A LOW of the drive signal during the other of the periods. However, it will be appreciated that, in accordance with the present disclosure, the drive signal can consist of a cyclic pattern of more than two consecutive periods, the drive signal having a substantially constant non-zero amplitude during each of the consecutive periods, and the amplitude of the drive signal during at least one of the periods being different from the amplitude of the drive signal during at least one other of the periods. For example, the drive signal can have a cyclic pattern of three consecutive periods. During each of the three consecutive periods, the drive signal can have a substantially constant non-zero amplitude. The amplitude of the drive signal during one of the periods can be different from the amplitude of the drive signal during the other two periods, or the amplitude of the drive signal can be different during all three periods.

[0069] Thus, the resulting drive magnetic field can have at least two distinct field strength values H LOW and H HIGH . The drive magnetic field can alternate between H LOW and H HIGH . The drive magnetic field can alternate according to a predetermined duty cycle. The drive coil 102 can output the drive magnetic field at an amplitude H HIGH for a first period T HIGH . The drive coil 102 can output the drive magnetic field at an amplitude H LOW for a second period T LOW . The duty cycle can be 50%, or in some implementations, the duty cycle can be between about 25% and about 75%. The total duty cycle period T HIGH + T LOW may be between about 10 ms and about 1000 ms. In some implementations, THIGH +T LOW may be about 100 ms. In Figure 4 In an example drive signal, T HIGH is shorter in duration than T LOW . Suitably, in some embodiments, the drive magnetic field can have a maximum field strength of between about 100 μΤ to about 2000 μΤ within about 5 mm of the probe 10, for example, H HIGH .

[0070] The harmonic filter and drive circuit 101 is configured to filter the drive signal and provide the drive signal to the drive coil 102. The harmonic filter is configured to reduce one or more additional frequency components f n from the drive signal. Suitably, the harmonic filter can be a notch filter tuned to a particular harmonic. The filtered drive signal is provided to the drive coil 102 to generate the drive field.

[0071] The base unit can also comprise one or more processing units; for example, a microcontroller and / or a field programmable gate array (FPGA). The base unit can also comprise a memory unit, an analogue-to-digital converter (ADC), and a digital-to-analogue converter (DAC). The memory unit may, for example, be formed from SDRAM or any suitable volatile or non-volatile storage means. The microcontroller can also control and interact with the computer memory. The microcontroller may, for example, be an STM32F769 microcontroller from STM Electronics, or any other suitable microcontroller. The microcontroller and FPGA can generate a sinusoidal drive signal which is then converted to an analogue signal by the DAC before being amplified; for example, using an operational amplifier.

[0072] The sense coil 104 is configured to generate an electrical sensed signal in response to the changing external magnetic field. The sense coil 104 is arranged to detect a response magnetic field generated by the magnetic material in response to the drive magnetic field. For example, the sense coil 104 can be arranged to detect a response magnetic field generated by the marker 6 and / or the tracer 7.

[0073] The detection probe 10 also comprises an electronic filter 106 (for example, a notch filter), and circuitry 108 for detecting and amplifying harmonic content. The electronic filter 106 can be suitably configured to reduce or remove the fundamental frequency f1 from the sensed signal to improve sensing of other frequency components f n of the sensed signal. The circuitry 108 for detecting and amplifying harmonic content can also amplify the additional frequency components f none or more harmonic frequencies corresponding to the fundamental frequency f1. The circuit can also suppress unwanted frequency components. The operation of the components used to process the sensed signal is described in more detail below.

[0074] Figure 5A A possible magnetization curve of the magnetic marker 6 is shown. The curve shows the magnetization level B of the marker 6 in relation to the strength of the applied external magnetic field H. The marker 6 can comprise at least one piece of large Barkhausen jump (LBJ) material. As mentioned above, the LBJ material can have a non-linear magnetization curve. According to the magnetization curve, an excitation field H below the switching field 25 will result in little or no change in the magnetization strength B, except for a small change in amplitude represented by the change from point 24 to point 25. In particular, an excitation field H below the switching field 25 will not affect a change in the polarity of the magnetization strength B of the marker 6. The magnetization curve shows a reversal of the magnetization once the switching field indicated with 25 is exceeded. The curve also shows a hysteresis effect, where the magnetization is further reversed once the switching field indicated with 30 is exceeded. In this way, the magnetization reversal of the marker 6 occurs regularly in time at half the period of the drive frequency (twice the frequency).

[0075] Figure 5B A typical sensed signal corresponding to the magnetization curve of Figure 5A is shown. When the marker 6 is excited by an alternating field having a sufficiently high amplitude (e.g., A HIGH ), a pulse corresponding to the magnetization reversal is seen in the time domain. The pulse is superimposed on a sinusoidal wave, even if the parasitic drive magnetic field coupled into the sensing coil is not completely filtered out. As discussed in more detail below, a material having a linear magnetic response would generate a sinusoidal sensed signal at the same frequency as the drive magnetic field. In comparison, the non-linear response of the marker 6 generates many harmonic frequency components in the sensed signal, which combine in a superimposed manner to generate the resulting pulsed signal, e.g., Figure 5B as shown in

[0076] Figure 5C A sensed signal corresponding to the magnetization curve of Figure 5A is illustrated in the frequency domain. In response to a drive magnetic field (e.g., H HIGH ) at substantially the fundamental frequency (f1), the sensed signal includes at least one additional frequency component at a high harmonic frequency. As indicated, the sensed signal can include a significant component in each of at least the 2ndharmonic frequency to the 10thharmonic frequency (f2 to f 10 ) relative to the fundamental frequency. Higher frequency components can also be present.

[0077] The marker 6 can be configured to, at a particular harmonic frequency (fx ) to provide an effective response. This harmonic frequency f x to distinguish a portion of the sensed signal generated by the marker 6 from another portion of the sensed signal that can be generated by one or more other secondary magnetic sources. For example, the harmonic frequency f x to distinguish the marker 6 from the tracer 7. In some implementations, the third harmonic frequency (f3) can be used to distinguish the marker 6 from the tracer 7.

[0078] The ratio between the fundamental response and the particular harmonic frequency f x in the response magnetic field generated by the marker 6 can be referred to as the marker response factor or primary response factor. The marker response factor can be approximately 100 or can be less than 100. In some implementations, the marker response factor can be less than 50, for example, the marker response factor can be approximately 30 before any filters are applied.

[0079] Instead of working in a bistable mode, in some implementations, the nonlinear marker can function in a sub-bistable mode. As described above, some LBJ materials exhibit a nonlinear response at fields less than the switching field (e.g., the third harmonic H3 response) that is almost two orders of magnitude larger than non-LBJ materials. This can allow for detection of markers further away from the probe 10 where the driving field is smaller, for example, below the switching field of the marker. However, to generate the excitation field at longer distances from the probe 10, the field amplitude near the probe 10 will be much higher.

[0080] Figure 6A A typical magnetization curve of the magnetic tracer 7 is shown. The curve shows the relationship of the magnetization level M of the tracer 7 to the strength of the applied external magnetic field H. The magnetic response of the tracer 7 is substantially linear at low excitation fields. In higher external magnetic fields, the magnetization of the tracer 7 can saturate because the nanoparticles in the tracer 7 are fully aligned with the external magnetic field. Thus, the magnetic response of the tracer 7 is linear at low excitation fields and can become nonlinear in response to higher excitation fields. According to the magnetization curve, a sinusoidal excitation field H with an amplitude below a certain linear threshold will result in a corresponding sinusoidal magnetization M. An excitation field with an amplitude above the linear threshold can generate distortions, i.e., nonlinearities, in the corresponding magnetization. Additionally, if the central portion of the magnetization curve is not linear (i.e., has a constant gradient), further nonlinear distortions can be generated in the corresponding magnetization.

[0081] Figure 6B A corresponding magnetization curve of the marker 6 is shown. The curve shows the relationship of the magnetization level M of the marker 6 to the strength of the applied external magnetic field H. The magnetic response of the marker 6 is substantially linear at low excitation fields. In higher external magnetic fields, the magnetization of the marker 6 can saturate because the nanoparticles in the marker 6 are fully aligned with the external magnetic field. Thus, the magnetic response of the marker 6 is linear at low excitation fields and can become nonlinear in response to higher excitation fields. According to the magnetization curve, a sinusoidal excitation field H with an amplitude below a certain linear threshold will result in a corresponding sinusoidal magnetization M. An excitation field with an amplitude above the linear threshold can generate distortions, i.e., nonlinearities, in the corresponding magnetization. Additionally, if the central portion of the magnetization curve is not linear (i.e., has a constant gradient), further nonlinear distortions can be generated in the corresponding magnetization. Figure 6AThe typical sensed signal is the magnetization curve of the tracer 7. When the tracer 7 is excited by an alternating field with an amplitude below a certain linear threshold mentioned in the preceding paragraphs, the sensed signal corresponds linearly to the excitation field. In the case where the alternating field has a sinusoidal form, the sensed signal therefore has a corresponding sinusoidal form. When the tracer 7 is excited by an alternating field with a sufficiently high amplitude, a pulse corresponding to the magnetization saturation of the tracer 7 can be observed in the time domain. The nonlinear response generates one or more harmonic frequency components in the sensed signal, which are superimposed to generate the final pulse signal.

[0082] Figure 6C Examples are given in the frequency domain and Figure 6A The sensed signal corresponds to the magnetization curve. As can be seen, in response to a low-amplitude driving magnetic field at the fundamental frequency (f1), the sensed signal mainly includes the fundamental frequency (f1). In response to a high-amplitude driving magnetic field at the fundamental frequency (f1), the sensed signal includes at least one additional frequency component at higher harmonic frequencies. As shown in the figure, the sensed signal can include at least the 2nd to 10th harmonic frequencies (f2 to f1) relative to the fundamental frequency. 10 A significant component at any harmonic frequency in the spectrum. In particular, significant components may exist at odd harmonic frequencies, especially in the third harmonic. Higher frequency components may also exist.

[0083] The harmonic frequency components in the sensed signal generated by tracer 7 can interfere with the detection of the harmonic frequency components generated by marker 6, and may hinder the accurate detection of marker 6.

[0084] As described above, marker 6 can be configured to operate at harmonic frequencies (f) x This provides an effective response. The harmonic frequency f can be... x The portion of the sensed signal generated by marker 6 is used to distinguish it from the portion generated by one or more other secondary magnetic sources. However, the portion generated by tracer 7 at harmonic frequency f... x The generation of sensed signal components may inhibit accurate detection of marker 6. Generating a driving magnetic field with an amplitude below the linear threshold for tracer 7 can reduce the generation of harmonic frequency components by tracer 7. In particular, using a low-amplitude driving magnetic field can reduce the generation of third harmonic frequency components by tracer 7. However, using a low-amplitude driving magnetic field may limit the detection range for detecting marker 6.

[0085] In the response magnetic field generated by tracer 7, the ratio between the fundamental frequency response and the third harmonic frequency can be referred to as the secondary response factor. As described above, the drive coil 102 can be configured to, during the corresponding time period T LOW With T HIGH Low-amplitude driving fields H are generated alternately during this period.LOW and high amplitude driving field H HIGH Based on the signal sensed by sensing coil 104 during that time period, and by transmitting the signal from T... LOW The response and from T HIGH By comparing the responses, the presence of a secondary source can be determined. For example, the presence of tracer 7 near probe 10 can be determined. The magnetic detection system 1 is configured to determine the presence of a secondary source based on the comparison of the response signals. LOW The response still came from T HIGH The response is appropriate so that marker 6 can be located.

[0086] If tracer 7 is confirmed to be present, use tracer from T LOW The response signal might be more suitable because tracer 7 responds to the driving field H. LOW The response may be more linear, and this will suppress less accurate detection of marker 6. Thus, more accurate detection can be achieved in the presence of a secondary magnetic source. If the absence of tracer 7 is determined, the signal from T... HIGH The response signal of the probe 10 might be more suitable because it allows for detection of marker 6 at a greater distance. This enables more accurate detection of marker 6 at distances from the probe 10 without the need for a secondary source.

[0087] Once a response signal is selected, marker 6 can be detected using information from the selected response signal (e.g., the ratio between harmonic components) according to this disclosure.

[0088] Figure 7 A block diagram of a magnetic detection system 1 according to an embodiment of the present disclosure is shown. The magnetic detection system 1 includes a frequency generator 110. An oscillator or waveform generator is a suitable example of the frequency generator 110. The frequency generator 110 is configured to generate an alternating signal during operation. This signal may be sinusoidal. The frequency f of the signal... D The frequency generator can operate in the range of 100Hz to 100kHz. A suitable example of a frequency generator is a microcontroller that outputs a sine wave, which is converted into an analog signal by a digital-to-analog converter (DAC), amplified by an analog amplifier, and filtered by a low-pass filter to smooth the signal. Alternatively, in some implementations, a digital amplifier may be used.

[0089] In use, frequency generator 110 amplifies the signal to one of one or more predetermined amplitude levels. According to embodiments, frequency generator 110 can amplify the signal to two or more amplitude levels in a time sequence. For example, the signal amplitude can be at a first amplitude level A. HIGH With the second amplitude level A LOW Alternating between them. First amplitude level AHIGH It can be greater than the second amplitude level A LOW First amplitude level A HIGH With the second amplitude level A LOW The ratio can be in the range of 1 to 10. For example, the ratio between amplitude levels can be 2. Advantageously, according to this disclosure, A HIGH and A LOW All are non-zero, as described below.

[0090] Frequency generator 110 can operate at a first amplitude level A HIGH The output signal reaches the first time period T HIGH and with the second amplitude level A LOW The output signal reaches the second time period T LOW In implementation, the first time period T HIGH Second time period T LOW They can be substantially equal in length. Alternatively, in some implementations, these time periods can be different in length. T HIGH With T LOW The ratio between these two values ​​can be called the signal duty cycle. The duty cycle can be expressed as the first time interval T in the total cycle. HIGH The percentage. The duty cycle can be, for example, approximately 25%, 50%, or 75%, or any other suitable value. Total time period T HIGH +T LOW It can be 100ms or less, so that the total refresh cycle time of the signal to the user can be maintained at a frequency of at least 10Hz, without significant hysteresis in terms of the magnetic response to the contrast change of the output signal.

[0091] In operation, the signal amplitude can be at the first amplitude level A. HIGH With the second amplitude level A LOW The signal alternates continuously without interruption. In some embodiments, the signal may cycle through two or more consecutive non-zero amplitudes that are distinct from each other to allow for differentiation between the marker 6 and the tracer 7 or other background magnetic sources, as described herein. However, this signal can advantageously never be interrupted while the system is in operation; that is, the signal may never have a zero amplitude. This can be important because the system of the present invention is used to detect minute changes in the magnetic field. Repeatedly applying voltage to the probe 10 during periods when there is no signal can lead to significant inaccuracies in the detection of the marker 6 due to thermal drift, which is caused by significant repeated thermal expansion and contraction of the material. Even slight changes caused by the thermal expansion / contraction of the probe 10 can significantly affect the accuracy of detection. According to the present invention, such thermal effects can be minimized by using two amplitudes, one after the other without interruption.

[0092] The generated signal excites one or more drive coils 120. The one or more drive coils generate an alternating magnetic field. The generated field extends into the tissue containing the magnetic marker 6, which includes at least one piece of large Barkhausen jump (LBJ) material. As described herein, the alternating magnetic field can be generated at two or more different amplitude levels corresponding to respective amplitude levels of the drive signal. For example, the magnetic field can be generated at a first amplitude level H HIGH and a second amplitude level H LOW corresponding to amplitude levels A HIGH and A LOW respectively.

[0093] The drive signal generated by the frequency generator 110 can be electronically filtered to attenuate any harmonic portions of the drive signal, such that the alternating magnetic field is primarily or substantially at the desired excitation or drive frequency. Filtering and processing of the drive signal can reduce any harmonic frequency components by orders of magnitude. This can help to avoid spurious responses at higher frequencies that can be misinterpreted as harmonic responses.

[0094] The alternating magnetic field excites the marker 6. Magnetization of the marker 6 causes generation of harmonic components in the response field, as described above. Depending on the arrangement of the marker 6, the harmonics can be odd harmonics (3rd harmonic, 5th harmonic, 7th harmonic, etc.) or even harmonics (2nd harmonic, 4th harmonic, 6th harmonic, etc.) or a combination of odd and even harmonics. The marker can be detected within the sensed signal, either by directly measuring the amplitude of one or more of the harmonic frequencies or by measuring the ratio of the amplitude of one or more harmonics to the amplitude of one or more other harmonics or to the amplitude of the fundamental frequency.

[0095] The alternating magnetic field can also excite the tracer 7. The tracer distribution in space is generally unknown. If the amplitude of the alternating magnetic field is below the linear threshold mentioned above for all tracers 7 in the volume surrounding the probe 10, the magnetic response of the tracer 7 is linear, independent of the distribution of the tracer in space. Magnetization of the tracer causes generation of a response field having a large fundamental frequency component in response to the drive magnetic field at the fundamental frequency.

[0096] However, if the amplitude of the alternating magnetic field is above the linear threshold for any tracer 7 in the volume surrounding the probe 10, the magnetic response of the tracer 7 can be nonlinear. The nonlinear response of the tracer 7 can result in one or more higher frequency components in response to the drive magnetic field. Thus, the response field generated by the tracer 7 in response to the drive magnetic field at the fundamental frequency can include one or more harmonic frequency components.

[0097] The response fields from the marker 6 and tracer 7 are detected by one or more sense coils 130 to produce a sense voltage or current. For example, the sense coils 130 can determine a first sensed signal S1 during a first time period T HIGH and a second sensed signal S2 during a second time period T LOW as described above. If the drive signal includes more than two different amplitudes, then additional sensed signals S n may be detected during additional time periods. The sense coils 130 can be disposed in a handheld or robotic probe, for example, as in the probe 10. An electronic filter 140 can be disposed to at least attenuate components at the drive frequency of the successive sensed signals, so that the resulting signal has minimal content at the drive frequency and includes higher harmonic components of the signal; for example, second harmonics, third harmonics, fourth harmonics, fifth harmonics, and seventh harmonics or permutations or combinations thereof. The filter 140 can take the form of a passive LCR type filter including known arrangements of, for example, capacitors, inductors, and resistors, or an active filter including known arrangements based on one or more operational amplifiers.

[0098] The filtered signals can be fed to a harmonic detection circuit 150 as shown in Figure 7 , which improves the signal-to-noise ratio of one or more harmonic components of the sensed signals S1, S2, S n and converts them to a measure of distance from the probe 10 to the marker 6. The harmonic detection circuit 150 can be configured to filter spurious harmonic responses generated by the tracer 7 or other background magnetic material. The harmonic detection circuit 150 can perform a number of operational steps. The functions of the harmonic detection circuit 150 can be performed by a microcontroller and FPGA, as described above.

[0099] The harmonic detection circuit 150 can be configured to perform a cross-correlation 151 for noise reduction. The harmonic detection circuit 150 can be configured to separate the successive sensed signals S1, S2, Sn into a plurality of frequency components by the cross-correlation 151. For example, the cross-correlation 151 can separate each of the signals into a fundamental harmonic signal 152 and at least one n-th harmonic signal 153.

[0100] The harmonic detection circuit 150 can be configured to perform a time period determination 154. This time period determination includes determining whether to use the first time period T HIGH or the second time period T LOW for locating the marker 6. For example, in the case of two different amplitudes A HIGH , A LOWIn the case that the first sensed signal S1 and the second sensed signal S2 are both generated by the magnetic marker 6, the period determination 154 can be based on a spectral analysis of the first sensed signal S1 and the second sensed signal S2. The analysed spectrum can be compared to a predetermined value (e.g. a known or expected value corresponding to the sensed signal). For example, the first sensed signal S1 and / or the second sensed signal S2 can be compared to a pre-recorded response from the isolated magnetic marker and the isolated secondary source.

[0101] The period determination 154 can be based on the fundamental harmonic signal 152 and at least one n-th harmonic signal 153 generated for each of the sensed signals S1 and S2. For example, a ratio between the fundamental harmonic signal 152 and the at least one n-th harmonic signal 153 can be calculated for each of the sensed signals S1 and S2. This ratio can be referred to as a harmonic ratio. The harmonic detection circuit 150 can be configured to calculate a first harmonic ratio R1 based on the fundamental harmonic signal 152 and the n-th harmonic signal 153 in the first sensed signal S1. The harmonic detection circuit 150 can be configured to calculate a second harmonic ratio R2 based on the fundamental harmonic signal 152 and the n-th harmonic signal 153 in the second sensed signal S2. In other embodiments, the period determination 154 can be based on two or more harmonic signals other than the fundamental harmonic signal generated for each of the sensed signals S1 and S2. For example, a ratio between the n-th harmonic signal 153 and another (n+x)-th harmonic signal (not shown) can be calculated for each of the sensed signals S1 and S2, where x is an integer, e.g. an odd or even number.

[0102] In some examples, the period determination 154 can be based on a comparison of R1 and R2. It can be determined that the response of the first sensed signal S1 is more linear than expected. For example, it can be determined that R1 is substantially higher than R2. This can indicate that a greater amount than expected of the fundamental harmonic signal 152 is being generated from the magnetic material that has been excited rather than the n-th harmonic signal 153, i.e. more of the excited magnetic material comprises non-LBJ material than expected. This can be indicative of the presence of a secondary source in the vicinity of the probe 10, where the secondary source is more linear than the marker 6. For example, this can be indicative of the presence of the tracer 7.

[0103] Based on the determined presence of the tracer 7, the period determination 154 can determine that the second period T LOW is more suitable for detecting the proximity of the marker 6.

[0104] In some examples, the period determination 154 can be based on a threshold for Rl. For example, the threshold can be based on an expected response of the marker 6. The marker 6 can generally have a designed or measured response ratio between the fundamental harmonic signal 152 and the nth harmonic signal 153. For example, a particular marker 6 can have a ratio in the range of 100 to 5000, or more specifically, an approximate ratio of 400 between, for example, the fundamental harmonic signal 152 and the third harmonic signal. The threshold for Rl can be set higher than this ratio, for example, higher than 400. An Rl value of the sensed signal greater than the threshold can indicate that there is more non-LBJ material present than expected for the marker 6 alone, indicating the presence of the tracer 7 or other secondary source of magnetic material.

[0105] In some cases, as discussed, the tracer 7 can exhibit a non-linear response during a first period T HIGH The non-linear response of the tracer 7 can be more linear than the response of the marker 6. In such cases, the presence of the tracer 7 can be determined based on a linear change between the first period T HIGH and the second period and T LOW .

[0106] In some examples, the period determination 154 can be based on the second sensed signal S2. The ratio R2 can be more linear than expected for the marker 6 alone. For example, R2 can be greater than the expected ratio of the marker 6. A threshold can be set for R2. An R2 value higher than the threshold can indicate the presence of the tracer 7.

[0107] In some examples, a minimum threshold can be applied to the nth harmonic signal 153 of either or both of the sensed signals S1 and S2. In this way, false switching can be avoided. For example, if the absence of the marker 6 results in the nth harmonic signal 153 being zero or at a background noise level, the ratio R1 or R2 can be unrealistically high.

[0108] If the presence of a secondary source is determined, for example, the presence of the tracer 7, the marker 6 can be located using only the second sensed signal S2. During the first period T HIGH , the nth harmonic signal 153 can include a component from the non-linear response of the tracer 7. It can be inappropriate to use the first sensed signal S1 from the first period T HIGH . The response of the tracer 7 in the second period T LOW may be assumed to be linear. The fundamental harmonic signal 152 can be ignored and the nth harmonic signal 153 from the second sensed signal S2 can be used to locate the marker 6.

[0109] If it is determined that there is no secondary source, e.g. no tracer 7, then the first sensed signal S1 and / or the second sensed signal S2 can be used to locate the marker 6. The time period determination 154 can determine a first time period T HIGH More suitably, a greater field strength H HIGH is used to increase the detection range of the marker 6.

[0110] In some embodiments, a second determination is made in this case. If the second sensed signal S2 is particularly high, then this can indicate that the marker 6 is in close proximity to the probe 10. The time period determination 154 can determine a second time period T LOW More suitably. In particular, only the second sensed signal S2 can be used as the marker 6 can be showing anomalous behaviour during the first time period T HIGH In some examples, the time period determination 154 can determine that it is suitable to use both the first time period T HIGH and the second time period T LOW More suitably.

[0111] A similar approach can be applied to reject spurious signals generated by different sources other than the tracer 7. For example, during a surgical procedure, linear signals can originate from metallic objects in the vicinity of the probe 10; from the patient’s body, from the surgeon’s hand or from a biopsy marker. The harmonic detection circuit 150 can reject any such signals that are sufficiently small so that they do not saturate the electronic components in the readout circuit.

[0112] The harmonic detection circuit 150 can also be configured to perform a signal transformation 155 on the n-th harmonic marker signal 154 to generate an output signal. The output signal may, for example, comprise a marker proximity value representing a measure of the distance from the probe 10 to the marker 6. The marker proximity signal can be as disclosed in co-pending international application no. PCT / GB2021 / 051750.

[0113] Accordingly, the output signal can include an audio signal and / or a display signal. The user display and sound generator 160 can provide visual and / or audio output to the user, for example, indicating the proximity of the marker 6 or the amplitude of the magnetic signal. The system can indicate the proximity, size, distance / direction, or orientation of the marker 6, or a combination of these. In some embodiments, the system can also indicate whether a secondary source is present based on the determination of the harmonic detection circuit 150. In some embodiments, the output signal can include a haptic signal. By selecting a more appropriate or most appropriate drive signal amplitude and ensuring that only the n-th harmonic frequency response is generated by the marker 6, the magnetic detection system 1 of the present disclosure can provide a significantly improved indication of the proximity, size, etc. of the marker 6. In some embodiments, the magnetic detection system 1 can accurately distinguish between the marker 6 and the tracer 7 so as to provide improved localization of the marker 6 in the presence of the tracer 7. In some cases, the magnetic detection system 1 can more accurately detect the marker 6 over a greater range in the absence of the tracer 7. The magnetic detection system 1 of the present disclosure can improve the accuracy of localizing the marker 6 and allow for more accurate removal of the corresponding lesion. Accordingly, the magnetic detection system 1 of the present disclosure can reduce the occurrence of excessive tissue removal by allowing the surgeon to more accurately determine the extent of the lesion, thereby improving recovery time and better surgical outcomes.

[0114] In other cases, the magnetic detection system 1 of the present disclosure can provide a more accurate indication of the size or amount of a magnetic marker, where the magnetic marker can correspond to a sample of any material that provides a non-linear magnetic response. The magnetic detection system 1 of the present disclosure can improve the determination of the size or amount even if the drive signal includes other spurious frequency components in addition to the desired fundamental frequency component.

[0115] In some embodiments, the system of the present disclosure can output an indication of the presence of a secondary source without making a determination using only the second sensed signal S2. For example, it can not be possible to perform the correction described above, for example, due to a too high secondary signal. In such cases, the system can provide an indication to the user that a secondary source can be causing interference.

[0116] Markers for use with the detection system of the present disclosure as described herein can each include one or more pieces of material that give a harmonic or non-linear response to an alternating magnetic field generated by a large Barkhausen discontinuity in their magnetization curve (“magnetic marker material”). Examples of such materials include glass-coated amorphous microwires that are iron-rich, cobalt-rich, and nickel-rich, iron-silicon-boron-based amorphous microwires, iron-cobalt-based amorphous microwires, and bulk metallic glass wires.

[0117] In some embodiments, the one or more pieces of magnetic marker material (formed from a material having a large Barkhausen discontinuity in its magnetization curve) can include a length of solid wire (<10 mm long) with a diameter <2 mm, such that the marker can be delivered through a small needle; a glass-coated micro-wire having a core diameter between, for example, 5 microns and 100 microns and a coating thickness between, for example, 0.5 microns and 40 microns; a bundle of two or more pieces of solid wire or glass-coated micro-wire; or a hollow tube.

[0118] Any of the markers can include more than one piece of magnetic marker material and additional material to connect or enclose the pieces of magnetic marker material and form the final outer shape of the marker. The marker can include a tube, multiple tubes, or a complete or partial shell of another material that holds the pieces of magnetic material within it. The marker can include electronic components, such as coils, diodes, and transistors; for example, an LC circuit (a combination of a capacitor and an inductor) with a diode can generate a non-linear response. The magnetic material can be coated or encapsulated in a biocompatible material. For example, a tube or shell containing the magnetic marker material can include a biocompatible malleable material such as 316 stainless steel, titanium, nitinol, titanium alloy, or the like.

[0119] In some embodiments, the probe 10 can include one or more drive coils 120. Alternatively, the alternating magnetic field can be generated by, for example, a spinning permanent magnet.

[0120] The probe 10 can include one or more sense coils 130, or alternatively, a solid-state magnetometer. In some implementations, the probe 10 can include any suitable magnetic sensor, such as a Hall effect sensor, a MEMS sensor, a magnetic transistor / magnetic diode, a SQUID magnetometer, an AMR (anisotropic magnetoresistance) sensor, or a GMR (giant magnetoresistance) sensor.

[0121] The drive frequency can be in the range of 100 Hz to 100 kHz. Higher frequencies toward 100 kHz can be advantageous for maximizing the sensed signal. Higher frequencies can also allow for more cycles per second to be averaged during detection to improve noise rejection, while still delivering a "real-time" output to the user, i.e., updating the output signal at least 10 times per second. Thus, for noise rejection, a frequency of at least 1000 Hz, and preferably at least 10 kHz, can be desirable. For example, to give the user a perceptible "real-time" response, the output can need to be updated at least once every 0.1 s. A frequency of 1 kHz allows for about 100 cycles to be averaged between each update to the user, and 10 kHz allows for 1000 cycles to be averaged between each update to the user.

[0122] Advantages can also be obtained from lower drive frequencies, and these include: reduced eddy current losses both in the marker (in situations where eddy currents are liable to be generated; for example if it has high electrical conductivity) and from surrounding tissue, and more intense magnetic switching in the marker. To reduce eddy current losses, frequencies less than 50 kHz and preferably less than 30 kHz can be advantageous. In a surgical theatre environment, electromagnetic interference signals can more frequently be experienced at frequencies above 100 kHz, so it can be beneficial to select a drive frequency such that the harmonics of interest are less than 100 kHz.

[0123] While aspects of the disclosure have been described herein with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present disclosure. It is therefore to be understood that numerous modifications can be made to the illustrative embodiments and that other arrangements can be devised without departing from the scope of the present disclosure as defined by the appended claims.

[0124] While various details have been set forth in the foregoing description, it will be appreciated that various aspects of the technology for operating a diagnostic and / or surgical guidance system adapted to identify, localize, track, and detect the position of one or more implanted markers can be practiced without these specific details. The person of skill in the art will recognize that the components, e.g., operations, apparatuses, objects, and the discussion accompanying them are used as examples for the sake of conceptual clarity and that various configuration modifications are contemplated. Consequently, as used herein, the specific exemplars set forth and the accompanying discussion are intended to be representative of their more general classes. In general, use of any specific exemplar is intended to be representative of its class, and the non-inclusion of specific components, e.g., operations, apparatuses, and objects, should not be taken to exclude those items from the claims. The claims should not be limited to the particular examples contained herein; the claims should be read as including any device elements that have substantially the same function in substantially the same way to achieve substantially the same results.

[0125] Moreover, while various forms have been illustrated and described, it is not the intention of the applicant(s) to limit or restrict the scope of the appended claims to such detail. Numerous modifications, alterations, variations, substitutions, combinations, and equivalents will be apparent to those skilled in the art in light of this disclosure without departing from the scope of the disclosure. Also, the structure of various elements associated with the described forms can be alternatively described as means for providing the function performed by the element. Likewise, where materials are disclosed for certain components, other materials can be used. Thus, the foregoing descriptions and the following claims are intended to cover all such modification, combinations, and variations as come within the scope of the disclosure. The claims should not be limited to the expressly claimed elements of the disclosure.

[0126] For the sake of brevity and clarity, some selected aspects of the foregoing disclosure are illustrated in block diagram form rather than in detail. Some portions of the detailed description provided herein can be presented in terms of instructions and other symbols drawn from memory of a base station or one or more processors or microprocessors operating in the base station, or one or more computer storage media, such as a floppy disk, a hard drive, a memory buffer, a RAM, a read-only memory (ROM), an erasable programmable read-only memory (EPROM), and other devices as will occur to persons skilled in the art. These descriptions and representations are used by those skilled in the art to more effectively convey the substance of their work to others skilled in the art. In general, a algorithm refers to a self-consistent sequence of steps leading to a desired result, where a "step" refers to a manipulation of physical quantities, and / or logic states, possibly represented by a machine, where the physical quantities and / or logic states can be stored, transferred, combined, compared, and otherwise manipulated, although not necessarily in that order. Commonly, the manipulations performed are often referred to as operations or symbolic representations of operations, and the associated memory elements can take various forms, depending on the particular technology of the machine or its

[0127] Unless specifically stated otherwise, as apparent from the preceding disclosure, it is appreciated that throughout the specified aspects, discussions utilizing terms such as "processing" or "computing" or "calculating" or "determining" or "displaying" or the like, refer to the action and processes of a computer system, or similar electronic computing device, that manipulates and transforms data represented as physical (electronic) quantities within the computer system's registers and memories into other data similarly represented as physical quantities within the computer system memories or registers or other such information storage, transmission or display devices.

[0128] In general, those skilled in the art will recognize that the various aspects described herein, which can be implemented by either software, firmware, hardware, or any combination thereof, can be viewed as being composed of various types of "electrical circuitry." Therefore, as used herein "circuitry" includes, but is not limited to, electrical circuitry having at least one discrete electrical circuit, electrical circuitry having at least one integrated circuit, electrical circuitry having at least one application specific integrated circuit (ASIC), electrical circuitry forming a general purpose computing device configured by a computer program (e.g., a general purpose computer configured by a computer program which at least partially carries out processes and / or devices described herein, or a microprocessor configured by a computer program which at least partially carries out processes and / or devices described herein), electrical circuitry forming a memory device (e.g., forms of random access memory), and / or electrical circuitry forming a communications device (e.g., a modem, communications switch, or optical-electrical equipment). Those having skill in the art will recognize that the subject matter described herein can be implemented in an analog or digital fashion or some combination thereof.

[0129] The foregoing detailed description has set forth various forms of the devices and / or processes described herein in the context of one or more particular implementations and their particulars. But, those skilled in the art will appreciate that the foregoing descriptions of various forms of the devices and / or processes described herein are not intended to limit the scope of the claimed subject matter, for the particular forms set forth in this detailed description are provided only as

[0130] Additionally, those skilled in the art will appreciate that the mechanism of the subject matter described herein can be distributed as one or more program products in one or more forms, and that exemplary forms of the subject matter described herein adapt to a particular type of signal-bearing media to realize one or more program interface(s) for accomplishing a particular operation. Examples of a program product include one or more of the following: a physically implemented and / or tangible computer-readable storage medium bearing computer program code examples, such as with one or more components, operable to

[0131] Also, as described, some aspects can be embodied as one or more methods. The acts performed as part of the method can be ordered in any suitable way. Accordingly, an embodiment of a method can be construed as comprising at least the acts described, even if those acts are performed in a different order from that depicted in the illustrative embodiments.

[0132] As used in this description and claims, the phrase "and / or" should be understood to mean "either or both" of the entities so conjoined, i.e., one entity alone, the other entity alone, or both entities together.

[0133] As used in this description and claims, the phrase "at least one", in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that the

[0134] The terms "approximately" and "about" can be used to mean within ±20% of the value of the cited number in some embodiments, within ±10% of the value of the cited number in some embodiments, within ±5% of the value of the cited number in some embodiments, and even within ±2% of the value of the cited number in some embodiments. The terms "approximately" and "about" can include the cited number.

[0135] In the claims, as well as in the specification above, all transitional phrases such as "comprising," "including," "carrying," "having," "containing," "involving," "holding," "composed of," and the like are to be understood to be open-ended, i.e., to mean including but not limited to. Only the transitional phrases "consisting of" and "consisting essentially of" are to be construed as closed or semi-closed transitional phrases, respectively.

[0136] Where a range of values is provided, for example, in a list of ranges or a list of values, each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range or the upper limit and another lower limit is also specifically contemplated by the disclosure as if each were individually listed. For example, "a range of from 1 to 10" is specifically contemplated as including each of the integers from 1 to 10, as well as fractions thereof, such as, for example, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, and 1.10. Likewise, a range of "7 to 11" is specifically contemplated to include each of the integers from 7 through 11, as well as fractions thereof, such as, for example, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 7.10, 7.11, 7.11, 7.12, 7.13, 7.14, 7.15, 7.16, 7.17, 7.18, 7.19, and 7.20. The same principle applies to ranges having an upper and lower limits that are not symmetrically disposed about a particular point. Listing the smaller values first does not preclude the larger values from being included in the range. Listing the larger values first does not preclude the smaller values from being included in the range.

[0137] The use of the title and section headings in this application are not to be construed as limiting the disclosure; each section can apply to any aspect, embodiment, or feature of the disclosure. Only those claims that use the phrase "apparatus for" are intended to be construed under 35 USC 112, paragraph 6, even in the United States only. Claims that do not recite "apparatus for" are not to be construed under 35 USC 112, paragraph 6. Outside the United States, the phrase "apparatus for" is intended to have its natural meaning. Limitations from the specification are not intended to be construed into any claim unless such limitations are explicitly included in the claim.

[0138] Embodiments disclosed herein can be implemented as a system, a method, or a computer program product. Therefore, embodiments can take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, micro-code, etc.) or an embodiment combining software and hardware aspects that can all generally be referred to herein as a "circuit," "module" or "system." Furthermore, embodiments can take the form of a computer program product on one or more computer readable medium(s) having computer readable program code embodied thereon.

[0139] While aspects of the present application have been described with reference to particular embodiments, it is to be understood that the embodiments are merely illustrative of the principles and applications of the present application. It is therefore to be understood that numerous modifications can be made to the illustrative embodiments and that other arrangements can be devised without departing from the scope of the present application as defined by the appended claims.

Claims

1. A method for detecting magnetic markers, the method comprising the following steps: A driving magnetic field is generated, the driving magnetic field having a cyclic pattern comprising two or more consecutive time periods, the driving magnetic field having a substantially constant non-zero amplitude during each of the consecutive time periods, and the amplitude of the driving magnetic field during at least one time period of the time period being different from the amplitude of the driving magnetic field during at least one other time period of the time period. Detect the response magnetic field; At least one signal is selected from a plurality of sensed signals, wherein each signal corresponds to the response magnetic field detected during a corresponding time period in the consecutive time periods of each cycle; the selected at least one signal is used to determine a detection signal corresponding to the magnetic marker; and an output signal is generated based on the intensity of the detection signal.

2. The method according to claim 1, wherein, The two or more consecutive time periods that form the cyclical pattern are substantially adjacent to each other.

3. The method according to claim 1 or claim 2, wherein, The amplitude of the driving magnetic field during at least one period of the continuous time period is higher than the amplitude of the driving magnetic field during at least one other period of the continuous time period.

4. The method according to claim 1 or claim 2, wherein, The amplitude of the driving magnetic field is relatively low during at least one other period of the continuous time period compared to the amplitude during at least one period of the continuous time period.

5. The method according to claim 1 or claim 2, wherein, The response magnetic field is detected across essentially the entire repeating pattern over a continuous time period.

6. The method according to claim 1 or claim 2, wherein, The durations of the consecutive time periods within each cycle are substantially the same or different from each other.

7. The method according to claim 1 or claim 2, wherein, The driving magnetic field has a substantially constant frequency throughout all time periods of the continuous time period.

8. The method according to claim 1 or claim 2, wherein, The cyclic mode includes two consecutive time periods, and the response magnetic field includes a first response component at a first frequency and a second response component at a second frequency, the second frequency being different from the first frequency.

9. A method for detecting magnetic markers, the method comprising the following steps: A driving magnetic field including a first frequency is generated, the driving magnetic field having a first amplitude lasting for a first time period and a second amplitude lasting for a second time period, the second amplitude being lower than the first amplitude, and the driving magnetic field alternating between the first amplitude and the second amplitude according to a predetermined duty cycle; The response magnetic field is detected, the response magnetic field including a first response component at a first frequency and a second response component at a second frequency, the second frequency being different from the first frequency; The processor selects at least one signal from a first sensed signal and a second sensed signal based on the response magnetic field, wherein the first sensed signal corresponds to the response magnetic field detected during the first time period and the second sensed signal corresponds to the response magnetic field detected during the second time period; The processor uses at least one selected signal to determine a detection signal corresponding to the magnetic marker; as well as The processor generates an output signal based on the strength of the detected signal for output.

10. The method according to claim 9, wherein, The first and second time periods are both less than one second each.

11. The method according to claim 9, wherein, The selection of at least one signal is based on the presence of an identifier secondary magnetic source.

12. The method according to claim 11, wherein, The secondary magnetic source is a liquid magnetic tracer.

13. The method according to claim 11 or claim 12, wherein, The step of identifying the presence of the secondary magnetic source includes: calculating the harmonic ratio between the first response component at the first frequency and the second response component at the second frequency.

14. The method according to claim 13, wherein, The step of identifying the presence of the secondary magnetic source includes: comparing a first harmonic ratio based on the first sensed signal with a second harmonic ratio based on the second sensed signal.

15. The method according to claim 11, wherein, The presence of the secondary magnetic source is identified by comparing the spectral analysis of the response magnetic field with pre-recorded responses from isolated magnetic markers and isolated secondary sources.

16. The method according to claim 9, wherein, The selection of the at least one signal is based on the absolute magnitude of the first sensed signal and / or the second sensed signal.

17. The method according to claim 16, wherein, The selection of the at least one signal is based on whether the absolute magnitude of the first sensed signal and / or the second sensed signal exceeds a predetermined threshold.

18. A magnetic detection system for detecting magnetic markers to guide a surgeon to an area of ​​interest during surgical procedures, the magnetic detection system comprising: A driving unit configured to generate a driving magnetic field based on a corresponding driving signal having a cyclic pattern comprising two or more consecutive time periods, wherein the driving signal has a substantially constant non-zero amplitude during each time period of the consecutive time periods, and the amplitude of the driving signal during at least one time period of the time period is different from the amplitude of the driving signal during at least one other time period of the time period. A magnetic field sensor, configured to detect a responding magnetic field; A processor configured to, based on the responding magnetic field, select at least one signal from a plurality of sensed signals, wherein each signal corresponds to the responding magnetic field detected during a corresponding time period in a series of consecutive time periods in a series of cycles; use the selected at least one signal to determine a detection signal corresponding to the magnetic marker; and generate an output signal based on the intensity of the detection signal.

19. The magnetic detection system according to claim 18, wherein, The two or more consecutive time periods that form the cyclic pattern of the drive signal are substantially adjacent to each other.

20. The magnetic detection system according to claim 18 or claim 19, wherein, The amplitude of the driving signal during at least one period of the continuous time period is higher than the amplitude of the driving signal during at least one other period of the continuous time period.

21. The magnetic detection system according to claim 18 or claim 19, wherein, The amplitude of the drive signal is relatively low during at least one other period of the continuous time period compared to the amplitude during at least one period of the continuous time period.

22. The magnetic detection system according to claim 18 or claim 19, wherein, The response magnetic field is detected across essentially the entire repeating pattern over a continuous time period.

23. The magnetic detection system according to claim 18 or claim 19, wherein, The durations of the consecutive time periods within each cycle are substantially the same or different from each other.

24. The magnetic detection system according to claim 18 or claim 19, wherein, The driving signal has a substantially constant frequency throughout all time periods of the continuous time period.

25. The magnetic detection system according to claim 18 or claim 19, wherein, The cyclic mode includes two consecutive time periods, and the response magnetic field includes a first response component at a first frequency and a second response component at a second frequency, the second frequency being different from the first frequency.

26. A magnetic detection system for detecting magnetic markers, the magnetic detection system comprising: A driving unit configured to generate a driving magnetic field including a first frequency, the driving magnetic field having a first amplitude lasting for a first time period and a second amplitude lasting for a second time period, the second amplitude being lower than the first amplitude, the driving unit generating the driving magnetic field by alternating between the first amplitude and the second amplitude according to a predetermined duty cycle; A magnetic field sensor configured to detect a response magnetic field, the response magnetic field including a first response component at a first frequency and a second response component at a second frequency, the second frequency being different from the first frequency; Processor, the processor being configured to: Based on the response magnetic field, at least one signal is selected from a first sensed signal and a second sensed signal, wherein the first sensed signal corresponds to the response magnetic field detected during the first time period and the second sensed signal corresponds to the response magnetic field detected during the second time period; At least one selected signal is used to determine the detection signal corresponding to the magnetic marker; as well as An output signal is generated based on the intensity of the detected signal.

27. The magnetic detection system according to claim 26, wherein, The first and second time periods are both less than one second each.

28. The magnetic detection system according to claim 26, wherein, The processor is configured to select the at least one signal based on the presence of an identifier secondary magnetic source.

29. The magnetic detection system according to claim 28, wherein, The secondary magnetic source is a liquid magnetic tracer.

30. The magnetic detection system according to claim 28 or claim 29, wherein, Identifying the presence of the secondary magnetic source includes: calculating the harmonic ratio between the first response component at the first frequency and the second response component at the second frequency.

31. The magnetic detection system according to claim 30, wherein, Identifying the presence of the secondary magnetic source includes comparing a first harmonic ratio based on the first sensed signal with a second harmonic ratio based on the second sensed signal.

32. The magnetic detection system according to claim 28, wherein, The presence of the secondary magnetic source is identified by comparing the spectral analysis of the response magnetic field with pre-recorded responses from isolated magnetic markers and isolated secondary sources.

33. The magnetic detection system according to claim 26, wherein, The processor is configured to select the at least one signal based on the absolute magnitude of the first sensed signal and / or the second sensed signal.

34. The magnetic detection system according to claim 33, wherein, The processor is configured to select the at least one signal based on whether the absolute amplitude of the first sensed signal and / or the second sensed signal exceeds a predetermined threshold.

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