Patent ID: 12207915

DETAILED DESCRIPTION

The present disclosure relates to a detection system and method for characterizing a marker, more particularly a magnetic marker, that can be implanted for marking a target site in the body, and to the detection and localisation of the implanted marker using a handheld probe.

The marker may be implanted in a site requiring marking in the body. This may, for example, be a tumour or other lesion or site of interest in soft tissue. Examples include, but are not limited to, benign lesions, cancerous lesions and lymph nodes. The marker may be placed in or near a lesion, or multiple markers may be placed to mark the margins or perimeter of a surgical site; for example the margins of a tumour or soft tissue sarcoma.

FIG.2of the accompanying drawings shows a schematic diagram of an embodiment of a detection system and marker according to the present disclosure. The detection system1comprises a probe10connected to a base unit4. The probe10has one or more drive coils that generate an alternating magnetic field to excite a magnetic marker6. A magnetic tracer7may also be present near or in the vicinity of the marker6.

The marker6comprises at least one piece of magnetically responsive material and may have anon-linear magnetic susceptibility. A magnetisation of the material may respond in a non-linear fashion to an external magnetic field. The material may have a large Barkhausen discontinuity in its magnetisation curve, and may be known as a “large Barkhausen jump material”, an “LBJ material”, a “bistable switching material” or a “material with large non-linearities in its magnetisation curve”. For example, when a length of LBJ material is exposed to an external magnetic field whose field strength opposing the instantaneous magnetic polarization of said length of material exceeds a predetermined threshold value, the switching field HSW, its magnetic polarization undergoes a rapid reversal. This reversal of magnetisation generates a magnetic pulse with intense harmonic components.

The tracer7typically comprises a liquid comprising a plurality of magnetic nanoparticles. For example, the tracer7may comprise a plurality of iron oxide nanoparticles. The tracer7is an example of a secondary magnetic source. In some cases, the tracer7may be considered to be a background magnetic source. The nanoparticles may be described as superparamagnetic nanoparticles. When the tracer7is exposed to an external field the magnetic response may be substantially linear; that is, the magnetisation of the tracer7is directly proportional to the applied field. The magnetic response of the tracer7may be substantially linear when a 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 tracer7may saturate, leading to a non-linear magnetic response.

The probe10of the detection system further contains one or more sense coils arranged to detect the changes in the magnetic field caused by the change in magnetisation of the marker6and/or tracer7.

To detect a marker6in a typical lesion or site of interest, the probe10should ideally have a detection depth of at least 30 mm, preferably more than 40 mm, and more preferably greater than 50 mm. Ideally, the marker6gives the same magnitude of response regardless of the direction in which the marker6is approached, i.e. it should have a low anisotropy of magnestisation. This is to provide consistent feedback to a surgeon as to the location of the marker6relative to the probe10.

FIG.3illustrates an example probe10in more detail. The detection probe10comprises a drive coil102to generate a driving magnetic field and a sense coil104to detect a response magnetic field.

The drive coil102is configured to generate the driving magnetic field by means of an applied electrical current, comprising a driving signal. The driving magnetic field is an alternating magnetic field generated to alternate at a fundamental frequency component f1. The drive coil102may suitably be configured to generate the driving magnetic field at one or more different output amplitudes.

The base unit4and probe10may further comprise a sine wave generator and amplifier100and a harmonic filter and drive circuit101, configured to generate the driving signal at the fundamental frequency f1. The sine wave generator and amplifier100is configured to generate and amplify an alternating current driving signal configured to alternate at the fundamental frequency f1. The amplifier100is configured to amplify the driving signal to one or more different amplitude levels. The amplifier100may be configured to amplify the driving signal to one of at least two distinct amplitude levels at a given time. For example, two distinct amplitude levels may be referred to as ALOWand AHIGH, wherein AHIGHis greater than ALOW. Advantageously, as described herein, the driving signal may oscillate between ALOWand AHIGHwithout interruption. Thus, AHIGHand ALOWmay both be non-zero. AHIGHmay suitably be of substantially constant amplitude. ALOWmay be of substantially constant amplitude. In some embodiments, the driving signal may have a continuous fundamental frequency f1.

By way of illustration, an example of a suitable, uninterrupted driving signal is illustrated inFIG.4. The driving signal ofFIG.4consists of a cyclic pattern of two successive periods of time during each of which the driving signal has a substantially constant, non-zero amplitude. The amplitude ALOWof the driving signal during one of the periods is different from the amplitude AHIGHof the driving signal during the other of the period of time. It will be appreciated however, that in accordance with the present disclosure, the driving signal may consist of a cyclic pattern of more than two successive periods of time, the driving signal having a substantially constant, non-zero amplitude during each of the successive periods of time, and the amplitude of the driving signal during at least one of the periods of time being different from the amplitude of the driving signal during at least one other of the periods of time. For example, the driving signal may have a cyclic pattern of three successive periods of time. During each of the three successive periods of time, the driving signal may have a substantially constant, non-zero amplitude. The amplitude of the driving signal during one of the periods of time may be different from the amplitude of the driving signal during the other two periods of time, or the amplitude of the driving signal may be different during all three periods of time.

The resulting driving magnetic field may therefore have at least two distinct field strength values HLOWand HHIGH. The driving magnetic field may alternate between HLOWand HHIGH. The driving magnetic field may alternate according to a predetermined duty cycle. The drive coil102may output the driving magnetic field at the amplitude HHIGHfor a first period of time THIGH. The drive coil102may output the driving magnetic field at the amplitude HLOWfor a second period of time TLOW. The duty cycle ratio may be 50% or, in some implementations it may be between about 25% and about 75%. The total duty cycle time period THIGH+TLOWmay be between about 10 ms and about 1000 ms. In some implementations THIGH+TLOWmay be about 100 ms. In the example driving signal ofFIG.4, THIGHis shorter in duration than TLOW. Suitably, in some embodiments, the driving magnetic field may have a maximum field strength, e.g. HHIGH, of between about 100 μT and about 2000 μT within about 5 mm of the probe10.

The harmonic filter and drive circuit101is configured to filter the driving signal and provide the driving signal to the drive coil102. The harmonic filter is configured to reduce one or more additional frequency components fnin the driving signal. Suitably, the harmonic filter may be a notch filter tuned to a specific harmonic. The filtered driving signal is provided to the drive coil102to generate the driving field.

The base unit may further comprise one or more processing units; for example, a microcontroller and/or a Field Programmable Gate Array (FPGA). The base unit may further 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 of SD RAM, or any suitable volatile or nonvolatile storage. The microcontroller may further control and interact with a computer memory. The microcontroller may, for example, be a STM32F769 microcontroller from STM Electronics, or any other suitable microcontroller. The microcontroller and FPGA may generate the sine wave drive signal which is then converted to an analogue signal by the DAC before being amplified; for example using an operational amplifier.

The sense coil104is configured to generate an electrical sensed signal in response to a varying external magnetic field. The sense coil104is arranged to detect a response magnetic field generated by a magnetic material in response to the driving magnetic field. For example, the sense coil104may be arranged to detect a response magnetic field generated by a marker6and/or a tracer7.

The detection probe10further comprises an electronic filter106, e.g. a notch filter, and a circuit to detect and amplify harmonic content108. The electronic filter106may suitably be configured to reduce or remove the fundamental frequency f1from the sensed signal, to improve the sensing of other frequency components fnof the sensed signal. The circuit to detect and amplify harmonic content108may further amplify one or more of additional frequency components fnof the sensed signal, e.g., corresponding to one or more harmonic frequencies of the fundamental frequency f1. The circuit may also suppress unwanted frequency components. The operation of the components for processing the sensed signal is described in more detail below.

FIG.5Ashows a possible magnetisation curve of the magnetic marker6. The curve shows the level of magnetisation B of the marker6in relation to the strength of an applied external magnetic field H. The marker6may comprise at least one piece of a large Barkhausen jump material (LBJ). As described above, the LBJ material may have a non-linear magnetisation curve. According to the magnetisation curve, an excitation field H which is lower than the switching field25will result in little or no change to the magnetisation B, except for a small change in magnitude which is represented by the change from point24to point25. In particular, an excitation field H which is lower than the switching field25will not effect a change in the polarity of magnetisation B of the marker6. The magnetisation curve shows a reversal of magnetisation once the switching field, indicated at25, is exceeded. The curve also shows a hysteresis effect, with a further reversal of magnetisation once the switching field indicated at30is exceeded. In this way, reversal of magnetization of the marker6occurs regularly in time with half the time period (double the frequency) of the driving frequency.

FIG.5Bshows a typical sensed signal corresponding to the magnetisation curve ofFIG.5A. When the marker6is excited by an alternating field with a sufficiently high amplitude, e.g. AHIGH, pulses corresponding to the reversal of magnetisation are seen in the time domain. The pulses may be superimposed onto a sine wave, if a spurious driving magnetic field coupled into the sense coils is not filtered out fully. As discussed in more detail below, a material having a linear magnetic response would produce a sinusoidal sensed signal at the same frequency as the driving magnetic field. In comparison, the non-linear response of the marker6produces many harmonic frequency components in the sensed signal, which combine in superposition to produce the resulting pulse signal, e.g. shown inFIG.5B.

FIG.5Cillustrates the sensed signal corresponding to the magnetisation curve ofFIG.5Ain the frequency domain. In response to the driving magnetic field, e.g. HHIGH, substantially at the fundamental frequency (f1), the sensed signal comprises at least one additional frequency component at a higher harmonic frequency. As indicated, the sensed signal may comprise a significant component in each of at least the 2nd to 10th harmonic frequencies (f2-f10) with respect to the fundamental frequency. Higher frequency components may also be present.

The marker6may be configured to provide a significant response at a specific harmonic frequency (fX) Such harmonic frequency fXmay be utilised to distinguish between a portion of the sensed signal generated by the marker6and another portion of the sensed signal which may be generated by one or more other secondary magnetic sources. For example, the harmonic frequency fXmay be utilised to distinguish between the marker6and the tracer7. In some implementations, the third harmonic frequency (f3) may be utilised to distinguish between the marker6and the tracer7.

In the response magnetic field generated by the marker6, a ratio between a fundamental frequency response and a particular harmonic frequency fXmay be referred to as a marker response factor, or primary response factor. The marker response factor may be approximately 100 or may be less than 100. In some implementations, the marker response factor may be less than 50, for example, the marker response factor may be approximately 30 before any filter is applied.

Instead of operating in bistable mode, in some implementations the non-linear marker may function in a sub-bistable mode. As described above, some LBJ materials still exhibit a non-linear response at fields smaller than the switching field (e.g. the third harmonic H3response) that is almost two orders of magnitude larger than for non-LBJ materials. This may allow detection of a marker which is further away from the probe10, where driving fields are smaller, e.g. below the switching field for the marker. However, to generate an exciting field at longer distances from the probe10, the field amplitude in proximity to the probe10will be much higher.

FIG.6Ashows a typical magnetisation curve for a magnetic tracer7. The curve shows the level of magnetisation M of the tracer7in relation to the strength of an applied external magnetic field H. The magnetic response of the tracer7is substantially linear at low excitation fields. In higher external magnetic fields, the magnetisation of tracer7may saturate, as the nanoparticles in the tracer7fully align with the external magnetic field. The magnetic response of the tracer7is therefore linear in a low excitation field, and may become non-linear in response to a higher excitation field. According to the magnetisation curve, a sinusoidal excitation field H, having an amplitude lower than a certain linear threshold will result in a corresponding sinusoidal magnetisation M. An excitation field having an amplitude higher than the linear threshold may produce distortions in the corresponding magnetisation, i.e. a non-linearity. In addition, if a central part of the magnetisation curve is not linear (i.e. having a constant gradient), then further non-linear distortions in the corresponding magnetisation may be produced.

FIG.6Bshows a typical sensed signal corresponding to the magnetisation curve ofFIG.6A. When the tracer7is excited by an alternating field with an amplitude lower than the certain linear threshold mentioned in the previous paragraph, the sensed signal corresponds linearly to the excitation field. Where the alternating field has a sinusoidal form, the sensed signal therefore has a corresponding sinusoidal form. When the tracer7is excited by an alternating field with a sufficiently high amplitude, pulses corresponding to saturation of the tracer7magnetisation may be seen in the time domain. The non-linear response produces one or more harmonic frequency components in the sensed signal, which combine in superposition to produce the resulting pulse signal.

FIG.6Cillustrates the sensed signal corresponding to the magnetisation curve ofFIG.6Ain the frequency domain. As can be seen, in response to the low-amplitude driving magnetic field substantially at the fundamental frequency (f1), the sensed signal comprises primarily the fundamental frequency (f1). In response to the high-amplitude driving magnetic field substantially at the fundamental frequency (f1), the sensed signal comprises at least one additional frequency component at a higher harmonic frequency. As shown, the sensed signal may comprise a significant component in any of at least the 2nd to 10th harmonic frequencies (f2-f10) with respect to the fundamental frequency. In particular, there may be a significant component in the odd harmonic frequencies, and in the third harmonic in particular. Higher frequency components may also be present.

Harmonic frequency components in the sensed signal generated by the tracer7can interfere with the detection of harmonic frequency components generated by the marker6, and may impede accurate detection of the marker6.

As described above, the marker6may be configured to provide a significant response in a harmonic frequency fX. The harmonic frequency fXmay be utilised to distinguish between the portion of the sensed signal generated by the marker6and the portion generated by one or more other secondary magnetic sources. However, generation of a sensed signal component at the harmonic frequency fXby the tracer7may inhibit accurate detection of the marker6. Generating a driving magnetic field with an amplitude below the linear threshold for the tracer7may reduce the generation of harmonic frequency components by the tracer7. In particular, using a low amplitude driving magnetic field may reduce the generation of third harmonic frequency components by the tracer7. However, using a low amplitude driving magnetic field may limit the detection range for detecting the marker6.

In the response magnetic field generated by the tracer7, a ratio between a fundamental frequency response and third harmonic frequency may be referred to as a secondary response factor. The driving coil102may be configured to generate alternately a low amplitude driving field HLOWand a high amplitude driving field HHIGHduring the respective time periods TLOWand THIGH, as described above. Based on the signals sensed by the sense coil104during the time, and by comparing the response from TLOWwith the response from THIGH, it can be determined whether a secondary source is present. For example, it can be established whether or not a tracer7is present in the vicinity of the probe10. The magnetic detection system1is configured to determine, based on the comparison of response signals, whether it is appropriate to use the response from TLOWor the response from THIGH, in order to localise the marker6.

In the event that a tracer7is determined to be present, it may be more appropriate to use the response signal from TLOW, because the response of the tracer7to the driving field HLOWmay be more linear, and will inhibit less accurate detection of the marker6. In this way, a more accurate detection may be achieved in the presence of a secondary magnetic source. In the event that a tracer7is determined to not be present, it may be more appropriate to use the response signal from THIGH, as this may allow the detection of a marker6at a greater distance. In this way, a more accurate detection of a marker6that is further away from the probe10may be achieved in the absence of a secondary source.

Once a response signal has been selected, the marker6may be detected in accordance with the present disclosure using information coming only from selected response signal (e.g. a ratio between harmonic components).

FIG.7shows a block diagram of a magnetic detection system1according to an embodiment of the present disclosure. The magnetic detection system1comprises a frequency generator110. An oscillator or a waveform generator is a suitable example of a frequency generator110. The frequency generator110is configured to generate an alternating signal in operation. The signal may be sinusoidal. A frequency fDof the signal may be in a range of 100 Hz to 100 kHz. A suitable example of a frequency generator is a microcontroller outputting a sine wave that is converted to an analogue signal by a digital-to-analogue (DAC) converter, amplified by an analogue amplifier and filtered by a low pass filter to smooth the signal. Alternatively, in some implementations a digital amplifier may be used.

In use, the frequency generator110amplifies the signal to one of one or more predetermined amplitude levels. According to an embodiment, the frequency generator110may amplify the signal to two or more amplitude levels in a time sequence. For example, the signal amplitude may alternate between a first amplitude level AHIGHand a second amplitude level ALOW. The first amplitude level AHIGHmay be larger than the second amplitude level ALOW. A ratio of the first amplitude level AHIGHto the second amplitude level ALOWmay be in the range of 1 to 10. For example, the ratio between amplitude levels may be 2. Advantageously, in accordance with the present disclosure, both AHIGHand ALOWare non-zero, as described below.

The frequency generator110may output the signal at the first amplitude level AHIGHfor a first time period THIGHand output the second amplitude level ALOWfor a second time period TLOW. In an implementation, the first time period THIGHand the second time period TLOWmay be substantially equal in length. Alternatively, in some implementations, the time periods may be different in length. A ratio between THIGHand TLOWmay be referred to as a duty cycle of the signal. The duty cycle may be expressed as a percentage of the total cycle that is the first time period THIGH. The duty cycle may be, for example, about 25%, 50% or 75%, or may be any other suitable value. The total period of time THIGH+TLOWmay be 100 ms or less in order that the overall refresh cycle time for the signal to the user can be maintained at a frequency of at least 10 Hz without a significant lag in the output signal versus the changing magnetic response.

In operation, the signal amplitude may alternate continually between the first amplitude level AHIGHand the second amplitude level ALOWwithout interruption. In some embodiments, the signal may cycle through more than two successive non-zero amplitudes which are different from one another to allow discrimination between the marker6and the tracer7or other background magnetic sources, as described herein. However, the signal may advantageously never be interrupted while the system is operating; that is, the signal may never have an amplitude of zero. This may be important because the system of the present disclosure is used to detect subtle changes of magnetic field. Repeatedly applying a voltage to the probe10with periods of no signal in between may lead to significant inaccuracies in detecting the marker6as a result of thermal drift, resulting from significant repeated thermal expansion and retraction of the materials. Even a slight change caused by thermal expansion/retraction of the probe10may have a dramatic effect on the accuracy of the detection. By using two amplitudes, one after the other without interruption according to the present disclosure, such a thermal effect may be minimised.

The generated signal excites one or more drive coils120. The one or more drive coils generate an alternating magnetic field. The generated field extends into tissue containing a magnetic marker6comprising at least one piece of a large Barkhausen jump material (LBJ). As described herein, the alternating magnetic field may be generated at two or more different amplitude levels corresponding to the respective amplitude levels of the driving signal. For example, the magnetic field may be generated at a first amplitude level HHIGHand a second amplitude level HLOWcorresponding respectively to the amplitude levels AHIGHand ALOW.

The driving signal generated by the frequency generator110may be electronically filtered to attenuate any harmonic parts of the drive signal so that the alternating magnetic field is primarily or substantially at the desired excitation or drive frequency. Filtering and processing of the driving signal may significantly reduce any harmonic frequency component by several orders of magnitude. This may help to avoid spurious responses at higher frequencies that could be erroneously interpreted as harmonic responses.

The alternating magnetic field excites the marker6. Magnetisation of the marker6leads to the generation of harmonic components in the response field, as described above. Depending on the arrangement of the marker6, the harmonics may be odd harmonics, (3rd, 5th, 7th etc.) or even harmonics (2nd, 4th, 6th etc.) or a combination of odd and even harmonics. The marker6may be detected by measuring the magnitude of one or more of the harmonic frequencies directly or by measuring a ratio of the magnitude of one or more harmonics to the magnitude of one or more other harmonics, or to the magnitude of the fundamental frequency, within the sensed signal.

The alternating magnetic field may also excite the tracer7. The tracer distribution in space is normally unknown. If the amplitude of the alternating magnetic field is below the above-mentioned linear threshold for all of the tracer7in a volume surrounding the probe10then a magnetic response of the tracer7is linear, independent of the distribution of the tracer in space. Magnetisation of the tracer leads to the generation of a response field with a large fundamental frequency component, in response to the driving magnetic field at the fundamental frequency.

However, if the amplitude of the alternating magnetic field is above the linear threshold for any of the tracer7in the volume surrounding the probe10then a magnetic response of the tracer7may be non-linear. A non-linear response of the tracer7may lead to one or more higher frequency components in response to the driving magnetic field. Thus, the response field generated by the tracer7may include one or more harmonic frequency components, in response to the driving magnetic field at the fundamental frequency.

The response field from the marker6and the tracer7is detected by one or more sense coils130to generate a sense voltage or current. For example, the sense coils130may determine a first sensed signal S1during the first time period THIGHand a second sensed signal S2during the second time period TLOWas described above. Further sensed signals Snmay be detected during further time periods if the driving signal comprises more than two different amplitudes. The sense coils130may be arranged in a handheld or robotic probe, such for example as the probe10. An electronic filter140may be arranged to attenuate at least components of the successive sensed signals at the drive frequency so that the resulting signals have minimal content at the drive frequency and comprise higher harmonic components of the signals; for example the second, third, fourth, fifth or seventh order harmonics or permutations or combinations of these. The filter140may take the form of a passive LCR type filter comprising a known arrangement of, for example, capacitors, inductors and resistors, or an active filter comprising a known arrangement; for example an arrangement based on one or more op-amps.

The filtered signals may be fed to a harmonic detection circuit150as shown inFIG.7, which improves the signal to noise ratio of one or more harmonic components of the sensed signals S1, S2, Sn and converts the signals to a measure of distance from the probe10to the marker6. The harmonic detection circuit150may be configured to filter a spurious harmonic response generated by the tracer7or other background magnetic material. The harmonic detection circuit150may perform a number of operational steps. The functions of the harmonic detection circuit150may be performed by a microcontroller and FPGA, as described above.

The harmonic detection circuit150may be configured to perform cross-correlation for noise reduction151. The harmonic detection circuit150may be configured to separate the successive sensed signals S1, S2, Sn into a plurality of frequency components by cross-correlation 151. For example, the cross correlation 151 may separate each of the signals into a fundamental harmonic signal152and at least one n-th harmonic signal153.

The harmonic detection circuit150may be configured to perform a time period determination154. The time period determination includes determining whether to use the first time period THIGHor the second time period TLOWfor localisation of the marker6. For example, where two different amplitudes AHIGH, ALOWare employed, time period determination154may be based on a spectral analysis of the first sensed signal S1and the second sensed signal S2. The analysed spectra may be compared with predetermined values, e.g., known or expected values corresponding to the sensed signals. For example, the first sensed signal S1and/or the second sensed signal S2may be compared with pre-recorded responses from an isolated magnetic marker and an isolated secondary source.

The time period determination154may be based on the fundamental harmonic signal152and at least one n-th harmonic signal153generated for each of the sensed signals S1and S2. For example, a ratio between the fundamental harmonic signal152and at least one n-th harmonic signal153may be calculated for each of the sensed signals S1and S2. The ratio may be referred to as a harmonic ratio. The harmonic detection circuit150may be configured to calculate a first harmonic ratio R1based on the fundamental harmonic signal152and an n-th harmonic signal153in the first sensed signal S1. The harmonic detection circuit150may be configured to calculate a second harmonic ratio R2based on the fundamental harmonic signal152and an n-th harmonic signal153in the second sensed signal S2. In other embodiments, the time period determination154may be based on two or more harmonic signals other than the fundamental harmonic signal, which are generated for each of the sensed signals S1and S2. For example, a ratio between the n-th harmonic signal153and a further (n+x)-th harmonic signal (not shown), where x is an integer, e.g. an odd integer or an even integer, may be calculated for each of the sensed signals S1and S2.

In some examples, the time period determination154may be based on a comparison of R1and R2. It may be determined that the response of the first sensed signal S1is more linear than expected. For example, it may be determined that R1is substantially higher than R2. This may indicate that, from the magnetic material that has been excited, a greater amount than expected is generating a fundamental harmonic signal152without generating an n-th harmonic signal153, i.e. more than expected of the excited magnetic material comprises non-LBJ material. This may be an indication of the presence of a secondary source in the vicinity of the probe10, where the secondary source is more linear than the marker6. For example, this may indicate that a tracer7is present.

Based on the determined presence of a tracer7, the time period determination154may determine that the second time period TLOWis more appropriate for detecting the proximity of the marker6.

In some examples, the time period determination154may be based on a threshold value for R1. For example, a threshold may be based on an expected response for the marker6. A marker6may typically have a designed or measured response ratio between the fundamental harmonic signal152and an n-th harmonic signal153. For example, a particular marker6may have a ratio in the range of 100 to 5000 or, more specifically, a ratio of approximately 400 between, e.g., the fundamental harmonic signal152and, say, a 3rd harmonic signal. A threshold value for R1may be set to be higher than this ratio, e.g. higher than 400. A value of R1for a sensed signal that is greater than the threshold may indicate the presence of more non-LBJ material than would be expected for the marker6alone, indicating the presence of a tracer7or other secondary source of magnetic material.

In some cases, as discussed, the tracer7may exhibit a non-linear response during the first time period THIGH. A non-linear response of the tracer7may be more linear than the response of the marker6. In such cases, it may be possible to determine the presence of the tracer7based on a change in linearity between the first and second time periods THIGHand TLOW.

In some examples, a time period determination154may be based on the second sensed signal S2. The ratio R2may be more linear than expected for the marker6alone. For example, R2may be greater than the expected ratio for a marker6. A threshold may be set for R2. A value of R2above the threshold may indicate the presence of a tracer7.

In some examples, a minimum threshold may be applied to the n-th harmonic signal153for either or both of the sensed signals S1and S2. In this way, false switching can be avoided. For example, if the absence of a marker6leads to an n-th harmonic signal153that is zero or is at the level of background noise, then the ratio R1or R2may be unrealistically high.

If it is determined that a secondary source is present, for example, a tracer7is present, then the marker6may be located using the second sensed signal S2only. During the first time period THIGH, the n-th harmonic signal153may include a component from a non-linear response of the tracer7. It may not be appropriate to use the first sensed signal S1from the first time period THIGH. The response of the tracer7in the second time period TLOWmay be assumed to be linear. The fundamental harmonic signal152may be disregarded and the marker6may be located using the n-th harmonic signal153from the second sensed signal S2.

If it is determined that a secondary source is not present, for example, a tracer7is not present, then the marker6may be located using the first sensed signal S1and/or the second sensed signal S2. The time period determination154may determine that the first time period THIGHis more appropriate, thereby to increase the detection range for the marker6using the greater field strength HHIGH.

In some embodiments, a second determination is made in this case. If the second sensed signal S2is particularly high, it may be an indication that the marker6is in very close proximity to the probe10. The time period determination154may determine that the second time period TLOWis more appropriate. In particular, the second sensed signal S2only may be used because the marker6may show anomalous behaviour at high driving fields during the first time period THIGH. In some examples, the time period determination154may determine that using both the first time period THIGHand the second time period TLOWis appropriate.

A similar methodology can be applied to reject spurious signals arising from different sources, other than a tracer7. For example, a linear signal could originate from metal objects that are in the proximity of the probe10during surgery; from the patient's body, from the surgeon's hands or from a biopsy marker. The harmonic detection circuit150may reject any such signals that are small enough that they do not saturate electronic components in the sense circuits.

The harmonic detection circuit150may be further configured to perform a signal conversion155on the n-th harmonic marker signal154to generate an output signal. The output signal may comprise, for example, a marker proximity value, which represents a measure of distance from the probe10to the marker6. The marker proximity signal may be as disclosed by copending International application no. PCT/GB2021/051750.

Thus, the output signal may comprise an audio signal and/or a display signal. A user display and sound generator160may provide a visual and/or audio output to the user indicating, for example, the proximity of the marker6or the magnitude of the magnetic signal. The system may indicate the proximity, size, distance/direction or orientation of the marker6, or combinations of these. In some embodiments, the system may further indicate whether or not a secondary source is present, based on the determination of the harmonic detection circuit150. In some embodiments, the output signal may comprise a haptic signal. By selecting the more or most appropriate driving signal amplitude, and ensuring that the n-th harmonic frequency response is generated only by the marker6, the magnetic detection system1of the present disclosure may provide a significantly improved indication of the proximity, size etc. of the marker6. In some embodiments, the magnetic detection system1may accurately distinguish between a marker6and a tracer7, in order to provide an improved localisation of the marker6in the presence of the tracer7. In some cases, the magnetic detection system1may more accurately detect a marker6at a greater range in the absence of a tracer7. The magnetic detection system1of the present disclosure may improve the accuracy of localising a marker6, and allow for a more accurate removal of a corresponding lesion. The magnetic detection system1of the present disclosure may thus reduce the occurrence of excess tissue removal, by allowing a surgeon to determine more accurately the extent of a lesion, thus improving recovery time and a better surgical outcome.

In other cases, the magnetic detection system1of the present disclosure may provide a more accurate indication of the size or quantity of a magnetic marker, where the magnetic marker may correspond to a sample of any material providing a non-linear magnetic response. The magnetic detection system1of the present disclosure may improve the determination of size or quantity, even when the drive signal includes a spurious frequency component in addition to the desired fundamental frequency component.

In some embodiments, the system of the present disclosure may output an indication that a secondary source is present, without making a determination to use the second sensed signal S2only. For example, it may not be possible to perform the above described correction, e.g., owing to unduly high secondary signals. In such cases, the system is able to provide an indication to the user that a secondary source may be causing interference.

The markers for use with the detection system of the the present disclosure as described herein may each comprise one or more lengths of material (“magnetic marker material”) which give a harmonic or non-linear response to an alternating magnetic field produced by a large Barkhausen discontinuity in their magnetisation curves. Examples of such materials include iron-, cobalt- and nickel-rich glass-coated amorphous microwires, iron-silicon-boron based amorphous microwires, iron-cobalt based amorphous microwires, and bulk metallic glass wires.

In some embodiments, the length or lengths of magnetic marker material (formed from a material with a large Barkhausen discontinuity in its magnetisation curve) may comprise a length of solid wire (<10 mm long) with a diameter <2 mm so that the marker can be delivered through a small needle; a glass-coated microwire with core diameter between, e.g., 5 and 100 micrometres, and a coating thickness of between, e.g., 0.5 and 40 micrometres; a bundle of two or more lengths of solid wire or glass-coated microwire; or a hollow tube.

Any of the markers may comprise more than one piece of magnetic marker material together with additional material to join or enclose the pieces of magnetic marker material and form the final outer shape of the marker. The marker may comprise a tube, tubes or a complete or partial shell of another material within which the lengths of magnetic material of the marker are held. The marker may comprise electronic components e.g. coils, diodes and transistors; for example an LC circuit (a combination of a capacitor and an inductor) with a diode may produce a non-linear response. The magnetic material may be coated or enclosed within a biocompatible material. For example, the tube or shell containing the magnetic marker material may comprise a biocompatible, plastically deformable material such as a 316 stainless steel, Titanium, Nitinol, Titanium alloy or similar.

In some embodiments, the probe10may comprise one or more drive coils120. Alternatively, an alternating magnetic field may be generated by, for example, a spinning permanent magnet.

The probe10may comprise one or more sense coils130or, alternatively, a solid state magnetometer. In some implementations, the probe10may comprise any suitable magnetic sensor, e.g., a Hall effect sensor, mems sensor, magneto-transistor/magneto-diode, a SQUID magnetometer, AMR (Anisotropic Magneto-Resistive) sensor, or a GMR (Giant Magneto Resistance) sensor.

The driving frequency may be in the range 100 Hz to 100 kHz. Higher frequencies towards 100 kHz may be advantageous to maximise the sensed signal. A higher frequency may also allow more cycles per second to be averaged during detection to improve noise suppression while still delivering a ‘real time’ output to the user, i.e. updating the output signal at least 10 times per second. Hence for noise suppression a frequency of at least 1000 Hz and preferably at least 10 kHz may be desirable. For example, in order to give an apparent ‘real time’ response to the user, the output may need to update at least every 0.1 s. A frequency of 1 kHz allows 100 cycles to be averaged between each update to the user, and 10 kHz allows 1000 cycles to be averaged between each update to the user.

Advantages may also be gained from a lower drive frequency, and these include reduced eddy current losses both in the marker (in cases where it is prone to eddy currents; for example if it has high conductivity) and from the surrounding tissue and more intense magnetic switching in the marker. For reduced eddy current losses, a frequency of less than 50 kHz and preferably less than 30 kHz may be advantageous. In an operating room environment, electromagnetic interference signals may be more frequently experienced at frequencies above 100 kHz and therefore choosing a drive frequency such that the harmonics of interest are less than 100 kHz may be beneficial.

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

While various details have been set forth in the foregoing description, it will be appreciated that the various aspects of the techniques for operating a diagnostic and/or surgical guidance system suitable for identifying, localizing, tracking, and detecting position of one or more implanted markers may be practised without these specific details. One skilled in the art will recognize that the herein described components (e.g., operations), devices, 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), devices, and objects should not be taken limiting.

Further, while several forms have been illustrated and described, it is not the intention of the applicant to restrict or limit the scope of the appended claims to such detail. Numerous modifications, variations, changes, substitutions, combinations, and equivalents to those forms may be implemented and will occur to those skilled in the art without departing from the scope of the present disclosure. Moreover, the structure of each element associated with the described forms can be alternatively described as a means for providing the function performed by the element. Also, where materials are disclosed for certain components, other materials may be used. It is therefore to be understood that the foregoing description and the appended claims are intended to cover all such modifications, combinations, and variations as falling within the scope of the disclosed forms. The appended claims are intended to cover all such modifications, variations, changes, substitutions, modifications, and equivalents.

For conciseness and clarity of disclosure, selected aspects of the foregoing disclosure have been shown in block diagram form rather than in detail. Some portions of the detailed descriptions provided herein may be presented in terms of instructions that operate on data that is stored in one or more computer memories or one or more data storage devices of the base station or the one or more processors or microprocessors operative therein (e.g. floppy disk, hard disk drive, caches, random access memory, and other optical and magnetic storage devices and media). Such descriptions and representations are used by those skilled in the art to describe and convey the substance of their work to others skilled in the art. In general, an 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 which may, though need not necessarily, take the form of electrical or magnetic signals capable of being stored, transferred, combined, compared, and otherwise manipulated. It is common usage to refer to these signals as bits, values, elements, symbols, characters, terms, numbers, or the like. These and similar terms may be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities and/or states. The various methods steps disclosed herein may be implemented or programmed as algorithms, data structures, and instructions that may operate upon inputs from data channels and generate outputs that contain various types of data such as user actional data, user feedback signals, information, and images.

Unless specifically stated otherwise as apparent from the foregoing disclosure, it is appreciated that, throughout the foregoing disclosure, discussions using 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, processor-based base station, 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.

In a general sense, those skilled in the art will recognize that the various aspects described herein which can be implemented, individually and/or collectively, by a wide range of hardware, software, firmware, or any combination thereof can be viewed as being composed of various types of “electrical circuitry.” Consequently, as used herein “electrical 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, 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 may be implemented in an analogue or digital fashion or some combination thereof.

The foregoing detailed description has set forth various forms of the devices and/or processes via the use of block diagrams, flowcharts, and/or examples. Insofar as such block diagrams, flowcharts, and/or examples contain one or more functions and/or operations, it will be understood by those within the art that each function and/or operation within such block diagrams, flowcharts, and/or examples can be implemented, individually and/or collectively, by a wide range of hardware, software, firmware, or virtually any combination thereof. In one form, several portions of the subject matter described herein may be implemented via an application specific integrated circuits (ASIC), a field programmable gate array (FPGA), a digital signal processor (DSP), or other integrated formats. However, those skilled in the art will recognize that some aspects of the forms disclosed herein, in whole or in part, can be equivalently implemented in integrated circuits, as one or more computer programs running on one or more computers (e.g., as one or more programs running on one or more computer systems), as one or more programs running on one or more processors (e.g., as one or more programs running on one or more microprocessors), as firmware, or as virtually any combination thereof, and that designing the circuitry and/or writing the code for the software and or firmware would be well within the skill of one of skill in the art in light of this disclosure.

In addition, those skilled in the art will appreciate that the mechanisms of the subject matter described herein are capable of being distributed as one or more program products in a variety of forms, and that an illustrative form of the subject matter described herein applies regardless of the particular type of signal bearing medium used to actually carry out the distribution. Examples of a signal bearing medium include, but are not limited to, the following: a recordable type medium such as a floppy disk, a hard disk drive, a Compact Disc (CD), a Digital Video Disk (DVD), a digital tape, a computer memory, etc.; and a transmission type medium such as a digital and/or an analogue communication medium (e.g., a fibre optic cable, a waveguide, a wired communications link, a wireless communication link (e.g., transmitter, receiver, transmission logic, reception logic, etc.), etc.).

Also, as described, some aspects may be embodied as one or more methods. The acts performed as part of the method may be ordered in any suitable way. Accordingly, embodiments may be constructed in which acts are performed in an order different than illustrated, which may include performing some acts simultaneously, even though shown as sequential acts in illustrative embodiments.

The phrase “and/or,” as used herein in the specification and in the claims, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases.

As used herein in the specification and in the 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 elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified.

The terms “approximately” and “about” may be used to mean within +20% of a target value in some embodiments, within ±10% of a target value in some embodiments, within +5% of a target value in some embodiments, and yet within +2% of a target value in some embodiments. The terms “approximately” and “about” may include the target value.

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. The transitional phrases “consisting of” and “consisting essentially of” shall be closed or semi-closed transitional phrases, respectively.

Where a range or list of values is provided, each intervening value between the upper and lower limits of that range or list of values is individually contemplated and is encompassed within the disclosure as if each value were specifically enumerated herein. In addition, smaller ranges between and including the upper and lower limits of a given range are contemplated and encompassed within the disclosure. The listing of exemplary values or ranges is not a disclaimer of other values or ranges between and including the upper and lower limits of a given range.

The use of headings and sections in the application is not meant to limit the disclosure; each section can apply to any aspect, embodiment, or feature of the disclosure. Only those claims which use the words “means for” are intended to be interpreted under 35 USC 112, sixth paragraph, and even then only in the United States. Absent a recital of “means for” in the claims, such claims should not be construed under 35 USC 112. Outside the United States, the words “means for” are intended to have their natural meaning. Limitations from the specification are not intended to be read into any claims, unless such limitations are expressly included in the claims.

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

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