Sensor apparatus

Abstract

A sensor apparatus comprises a thermal conditioner, a temperature sensor and a controller. The thermal conditioner is configured to thermally condition a fluid. The temperature sensor is configured to sense the thermally conditioned fluid. The controller may be configured to control the thermal conditioner to thermally condition the fluid at a timing based on a cardiac signal indicative of a cardiac cycle.

Description

[0001] SENSOR APPARATUS

[0002] Field

[0003] The present application relates to a sensor apparatus, for example for measuring a flow of a fluid in a physiological environment, such as within a vessel of a human or animal subject.

[0004] Background

[0005] The flow of fluids in vessels within the human body yields physiological parameters that are clinically important for diagnostic and therapeutic purposes. For instance, measurements of blood flow in the coronary arteries can be used to assess the severity of a stenosis and thereby to assist with a decision about whether to place a stent. Similarly, measurement of cardiac blood flow is extremely valuable for monitoring a critically ill patient or during major surgery. As an example, the effective stroke volume may be determined from the blood flow in the aorta, and based on the variation of the aortal flow over time, a conclusion may be drawn concerning the rate of cardiac insufficiency, the haemodynamic effects of arrhythmia, possible treatment parameters, and / or the vascular characteristics of the aorta. As another example, the blood flow in the renal arteries is an important parameter for the diagnosis and treatment of renal insufficiency. A complete assessment and appreciation of the haemodynamics of a blood vessel requires knowledge of both pressure and fluid dynamics. An ideal device for providing these measurements would be small in lateral extent, provide highly accurate data which are stable and robust, be inexpensive to manufacture, and immune to interference such as electromagnetic interference. Currently available measurement devices fall short of this ideal for various reasons.

[0006] Coronary heart disease remains the leading cause of death worldwide. Patient symptoms occur when a build-up of cholesterol plaque restricts coronary blood flow, or from disease in the microvasculature. Clinicians' decisions about treatment are often guided by data from medical devices placed inside the arteries, but these only provide information about differences in blood pressure in large coronary arteries. However, the diagnosis is incomplete and a large patient population remains underserved: those with angina and / or signs of ischemia at least partially due to disease in the microvasculature. There is an increasing interest in the understanding of the flow within coronary arteries with an aim of being able to better guide treatment when the full physiological metrics of coronary flow are understood.

[0007] Invasive flow is challenging to measure routinely with currently available systems. Doppler wires use piezoelectric transducers to sense flow velocity: signals are often too weak to interpret reliably, they lack mechanical robustness, and they have poor reproducibility in non-expert hands. Another invasive flow sensing method is thermodilution in which cool saline is injected upstream and flow is measured from downstream temperature data. Thermodilution is widely seen as impractical, cumbersome and inaccurate, the complexities in reliably performing these studies hinders uptake of this technology.

[0008] There are significant limitations with current solutions: pressure-only assessments ignore disease of the downstream microvasculature, thereby giving only a very incomplete diagnostic picture. Patients may therefore be falsely reassured, be left undertreated or completely undiagnosed. Certain groups are disproportionately affected, e.g. women and diabetics, who present with more microvascular disease and atypical symptoms; they are less likely to be suitable for treatment with a percutaneous coronary intervention. The unmet need is prominent in the UK and worldwide.

[0009] Current invasive flow measurement methods are imprecise and clumsy, limiting their widespread use. As a result, ischemia with no obstructive coronary arteries is severely underdiagnosed. This underdiagnosis holds back the application of precision approaches for large groups of patients.

[0010] Non-invasive tests are complementary to invasive techniques. Current tests are known to be inaccurate for the large number of cases where fractional flow reserve and instantaneous wave-free ratio values are close to clinical decision thresholds, so there remains a large and growing demand for invasive flow sensors.

[0011] Summary

[0012] According to an aspect of the present invention there is provided a sensor apparatus comprising: a thermal conditioner configured to thermally condition a fluid; a temperature sensor configured to sense the thermally conditioned fluid; and a controller configured to control the thermal conditioner to thermally condition the fluid at a timing based on a cardiac signal indicative of a cardiac cycle.

[0013] According to another aspect of the present invention there is provided a sensor apparatus comprising: a thermal conditioner configured to thermally condition fluid; a temperature sensor configured to sense the thermally conditioned fluid; and a controller configured to control the thermal conditioner to thermally condition the fluid at a timing based on a hyperaemia signal indicative of a hyperaemic cardiac condition.

[0014] According to another aspect of the present invention there is provided a sensor apparatus comprising: a thermal conditioner configured to thermally condition a fluid by outputting pulses; a temperature sensor configured to measure a temperature of the thermally conditioned fluid; and a controller configured to receive a temperature signal from the temperature sensor indicative of heating of the temperature sensor by the pulses from the thermal conditioner and cooling of the temperature sensor due to heat transfer with the fluid flowing past the temperature sensor, and to measure a parameter of flow of the fluid based on the received temperature signal.

[0015] According to another aspect of the present invention there is provided a sensor apparatus comprising: a thermal conditioner configured to thermally condition a fluid; a temperature sensor configured to measure a temperature of the thermally conditioned fluid; and a controller configured to receive a temperature signal from the temperature sensor, to control a level of thermal conditioning by the thermal conditioner such that the received temperature signal is substantially constant, and to measure a parameter of the fluid over time based on the level of thermal conditioning by the thermal conditioner over time.

[0016] According to another aspect of the present invention there is provided a sensor apparatus comprising: a thermal conditioner configured to thermally condition a fluid; a temperature sensor configured to measure a temperature of the thermally conditioned fluid; and a controller configured to control the thermal conditioner to have an output having a periodicity, to receive a temperature signal from the temperature sensor and to measure a parameter of the fluid over time by resolving the periodicity of the output of the thermal conditioner from the received temperature signal.

[0017] According to another aspect of the present invention there is provided a sensor apparatus comprising: a guidewire; a thermal conditioner on the guidewire configured to thermally condition a fluid; and a temperature sensor on the guidewire configured to sense the thermally conditioned fluid; wherein the sensor apparatus is configured such that a distance along the guidewire between the thermal conditioner and the temperature sensor is adjustable.

[0018] Embodiments of the present invention can provide direct information about both blood flow and blood pressure. Direct measures of blood flow have been shown to be valuable to significantly improve clinical decision- making about whether to place a coronary stent and assess the health of smaller vessels (coronary microvascular dysfunction). Flow metrics can improve outcomes when used to target treatment in acute patients and also give valuable prognostic information.

[0019] Brief Description of the Drawings

[0020] Various implementations of the invention will now be described in detail by way of example only with reference to the following drawings:

[0021] Figure 1 schematically depicts a sensor apparatus according to an embodiment of the invention.

[0022] Figure 2 schematically depicts a temperature sensor of the sensor apparatus of Figure 1.

[0023] Figures 3-6 schematically depict the sensor apparatus of Figure 1 at different stages of use.

[0024] Figure 7 is a graph showing the relationship between time and temperature difference.

[0025] Figure 8 is a graph showing the relationship between sequential measurements and a plateau length of the temperature change curve.

[0026] Figure 9 is a graph showing the relationship between time and temperature change for different measurements. Figure 10 is a schematic graph showing different metrics that may be measured from the temperature change curve.

[0027] Figure 11 is a graph showing the relationship between the phase of the cardiac cycle and the time to the maximum upstroke of the temperature change curve.

[0028] Figure 12 schematically depicts a workflow of automatic hyperaemia detection.

[0029] Figure 13 is a graph showing the relationship between time and temperature change when the flow rate is doubled.

[0030] Figure 14 is a graph showing the relationship between time and pressure change when the flow rate is doubled.

[0031] Figure 15 is a graph showing the relationship between time and aortic pressure during the cardiac cycle.

[0032] Figure 16 is a graph showing the relationship between time and coronary flow during the cardiac cycle.

[0033] Figure 17 is a graph showing the relationship between time and temperature change during continuous use of the sensor apparatus.

[0034] Detailed Description

[0035] Described herein is a sensing device which may be used as an implanted (inserted) sensor for measuring physiological parameters within the body. One implementation of such a device may be used to perform flow and pressure measurements within a living body, such as for determining the flow speed or volumetric flow rate of the blood in a blood vessel, or the flow of urine within the urinary tract.

[0036] Figure 1 schematically depicts a sensor apparatus according to an embodiment of the invention. As shown in Figure 1, in an embodiment the sensor apparatus 10 comprises a thermal conditioner 120. The thermal conditioner 120 is configured to thermally condition a fluid. For example, the thermal conditioner 120 may be configured to heat the fluid. The fluid may be a liquid such as blood.

[0037] The sensor apparatus 10 is configured to measure one or more parameters of the fluid. For example, the sensor apparatus 10 may be configured to measure physiological parameters within a body. The parameters may be flow speed or volumetric flow rate of blood in a blood vessel, the flow of urine within the urinary tract, or a pressure measurement, for example. As shown in Figure 1, the sensor apparatus 10 may comprise a temperature sensor 100. The temperature sensor 100 is configured to sense the thermally conditioned fluid. For example, the temperature sensor 100 may detect a change in temperature of the flow of fluid. In Figure 1, the fluid flow is shown schematically by the arrow 175.

[0038] As shown in Figure 1, the thermal conditioner 120 may generally be located upstream of the temperature sensor 100. The thermally conditioned fluid flows generally from the thermal conditioner 120 in the direction of the temperature sensor 100. The thermal conditioning of the fluid may be referred to as thermal tagging. The temperature sensor 100 is configured to detect the thermally tagged fluid. The one or more parameters may be determined from the output of the temperature sensor 100.

[0039] The sensor apparatus 10 may comprise a catheter, which may be referred to as a microcatheter. The temperature sensor 100 may be secured to the catheter. The diffuser 123 of the thermal conditioner 120 may be secured to the microcatheter.

[0040] Figure 2 schematically shows a close up view of an implementation of the temperature sensor 100. The sensor apparatus 10 may comprise an optical fibre 110. The optical fibre 110 may extend between the thermal conditioner 120 and the temperature sensor 100. The optical fibre 110 may serve as an interrogation light guide. The optical fibre 110 may be configured to transmit interrogation light, for example of multiple wavelengths, to the temperature sensor 100. The optical fibre 110 may be configured to receive reflected interrogation light.

[0041] As shown in Figure 2, a coating 120 may cover the distal end of the optical fibre 110. The coating 110 may be formed, for example, from an elastic polymer having a relatively high linear expansion coefficient, such as polydimethylsiloxane. The coating may be a structure which is manufactured at the distal end of the fibre, or may be cavity injected or otherwise attached or moulded onto the distal end of the optical fibre 110. The coating 120 has a first reflective surface 130 at the fibre-coating interface and a second reflective surface 140 at the interface between the coating 120 and a cavity 170.

[0042] The two surfaces 130, 140 oppose each other such that they are substantially parallel to each other, both lying in the plane perpendicular to the main longitudinal axis of the optical fibre 110. The temperature sensor 100 may further include a membrane 125 positioned distal to the coating 120. The membrane 125 has a third reflective surface 135. The membrane 125 may be fixed to the distal end of the optical fibre 110 using a capillary 115. The cavity 170 is located proximal to the membrane 125.

[0043] The temperature sensor 100 may be inserted into a vessel filled with a fluid. As shown in Figure 1, the temperature sensor 100 may be provided on a guidewire 160.

[0044] The optical fibre 110 is configured to provide interrogation light 150 to the temperature sensor 100. At least some of the interrogation light 150 is reflected back from the membrane 125.

[0045] Pairs of reflective surfaces, from both the coating 120 and the membrane 125, form respective etalons. For example, one etalon is formed from the second reflective surface 140 and the third reflective surface 135. Another etalon is formed from the interrogation light 150 which is reflected at the first reflective surface 130 and the second reflective surface 140 of the coating 120. The reflected interrogation light 155 is then transmitted back through the optical fibre 110 towards the proximal end of the optical fibre 110.

[0046] The deflection of the membrane 125 towards or away from the proximal end is dependent on the pressure of the fluid. For example, if high pressure is applied to the membrane 125 by the fluid, the cavity 170 is compressed, thereby reducing the optical path between the first reflective surface 130 or the second reflective surface 140 and the third reflective surface 135.

[0047] Excitation light may be provided through an optical fibre 122 (see Figure 1) of the thermal condition 120. The excitation light may be transmitted to a diffuser 123 of the thermal conditioner 120 to increase the temperature of the surrounding fluid. The fluid may be heated optically. This is different from direct heating of the temperature sensor electrically. The etalon formed by reflective surfaces of the membrane 125, for example, can be used to obtain measurements of temperature changes. Temperature changes (e.g. by thermal expansion) can cause deformation of the temperature sensor 100, which can be measured by the interrogation light reflected by the reflective surfaces.

[0048] As shown in Figure 1, the sensor apparatus 10 may comprise an excitation light source 121. The excitation light source 121 is configured to output excitation light for thermally conditioning the fluid. The excitation light source 121 may be referred to as a tagging input. The excitation light source 121 may comprise a laser, for example. As shown in Figure 1, in an embodiment the thermal conditioner 120 comprises an optical fibre 122. The optical fibre 122 is configured to transmit the excitation light from the excitation light source 121 to the diffuser 123. The diffuser 123 is configured to diffuse the excitation light 124 into the fluid for heating the fluid.

[0049] As shown in Figure 1, the sensor apparatus 10 may comprise an interrogation light source and spectrometer 130. The interrogation light source may comprise a light emitting diode, for example. The interrogation light source may be configured to output interrogation light. The interrogation light may be transmitted via an optical fibre 135 towards the temperature sensor 100. The optical fibre 135 may be formed continuously with the optical fibre 110 shown in Figure 2. The spectrometer may be configured to receive reflective interrogation light 155 so as to measure the one or more parameters of the fluid.

[0050] The sensor apparatus 10 may comprise a microcatheter and a consol e / display that provides physicians with the data to make a complete coronary diagnosis in a manner that is fully compatible with current clinical practice.

[0051] During use of the sensor apparatus 10, the surfaces within the temperature sensor 100 undergo deformations in response to temperature and pressure variations. These deformations, typically at the nanometre scale, are measured using light transmitted via the optical fibre 110. Reflections are detected by the spectrometer. Calculations may be performed to determine the pressure and / or temperature.

[0052] Blood flow measurements are performed by warming of the fluid at a position upstream from the temperature sensor 100. The sensor records this change in temperature downstream. The energy used to generate temperature increases is provided optically, by delivering light directly into the fluid where it is absorbed.

[0053] Figures 3-6 schematically show different stages of operation of the sensor apparatus 10. Figure 3 shows the sensor apparatus 10 before the excitation light thermally conditions the fluid. Figure 4 shows the point at which the excitation light reaches the diffuser 123 and the fluid is thermally conditioned (or tagged). The thermally conditioned fluid 174 is shown in Figure 4. Figure 5 shows the thermally conditioned fluid 174 flowing towards the temperature sensor 100. Figure 6 shows the thermally conditioned fluid 174 having flowed past the temperature sensor 100.

[0054] Figure 7 is a graph showing the relationship between time and temperature change measured by the temperature sensor 100. The temperature change AT is measured as the thermally conditioned fluid 174 flows past the temperature sensor 100. The flow rate may be determined from the time difference between when the temperature change is measured and the fluid was thermally tagged. The distance between the diffuser 123 and the temperature 100 may be known.

[0055] The sensor apparatus 10 may comprise a controller. The controller may be configured to control the thermal conditioner 120 to thermally condition the fluid at a timing based on a cardiac signal indicative of a cardiac cycle. The relationship between time and temperature change AT measured by the temperature sensor 100 may depend on the timing of the thermal tagging relative to the cardiac cycle. The fluid pressure and the fluid flow rate may vary during the cardiac cycle. As a result, the measurements made by the sensor apparatus 100 may be dependent on the timing of the measurements relative to the phase of the cardiac cycle.

[0056] The sensor apparatus 10 produces thermal perturbations in the coronary blood flow by emitting excitation light (which may be near infra red light) into the blood via the diffuser 123. The excitation light source may produce the 50-400ms pulse of NIR light. Thermal tagging can be provided at fixed points within the cardiac cycle, fixed intervals or at preset intervals.

[0057] Arterial blood flow is pulsatile. The flow in the coronary arteries has a complex waveform, affected by the aortic pressure and by the varying resistance in the small vessels of the cardiac mi crovasculature .

[0058] By controlling the thermal conditioner 120 to thermally condition the fluid at a timing based on a cardiac signal indicative of a cardiac cycle, the phase of the cardiac cycle can be taken into account. This may allow measurements made by the sensor apparatus 10 to be compared more validly with each other. The accuracy of measurements of parameters of the fluid may be improved. For example, a baseline measurement may be compared more validly to a measurement made during hyperaemia.

[0059] A particular point in the cardiac cycle may be selected. The controller may be configured to control the thermal conditioner 120 to thermally condition the fluid at that selected point. The measurement may be repeated using the same selected point. The sensor apparatus 100 may provide a cleaner measurement signal by gating the sensing to the cardiac cycle.

[0060] The controller may be configured to synchronise timings at which the thermal conditioner 120 thermally conditions the fluid with the cardiac cycle. For example, repeated measurements may be made at the same point within the cardiac cycle. The point may refer to a particular phase of the cardiac cycle. By using the same point, the variation in fluid pressure and fluid flow rate between the measurements may be expected to be reduced.

[0061] The controller may be configured to control the thermal conditioner 120 based on the cardiac signal to thermally condition the fluid at different points in the cardiac cycle. For example, the sensor apparatus 10 may thermally condition the fluid so as to make measurements with varying intervals between the measurements.

[0062] The interactions between thermal tagging, the heart cycle, the electrocardiogram, the pressure waveform and the coronary blood flow can be governed by synchronising the thermal tagging pulse with the electrocardiogram or pressure wave, either aortic or local. Alternatively, the thermal tagging can be triggered by the electrocardiogram or pressure waveforms. Sequential pulses can allow a thermal tagging to be performed at different times in the cardiac cycle and thereby the variation in thermal transit curves measured with the pulse timing to be determined.

[0063] Figure 8 is a graph showing the relationship between sequential measurements and a plateau length of the temperature change curve measured by the temperature sensor 100. As shown in Figure 7, the temperature change may plateau near its peak. The length of the plateau may be measured. The length of the plateau may vary depending on the phase of the cardiac cycle when the measurement is taken. Figure 8 shows that the plateau length varies among the different sequential measurements. The different measurements are made at different points in the cardiac cycle.

[0064] Figure 9 is a graph showing the relationship between time and temperature change AT measured by the temperature sensor 100 for different measurements. The different measurements are the same different measurements shown in Figure 8. The different measurements may be made at different phases of the cardiac cycle. Sequential pulses may be spread in a pseudo random manner, e.g. at a fixed timing interval plus a sequentially or decreasing timing interval until the entire cardiac cycle is likely to be accounted for in a sufficient density for inferences to be made. As shown in Figure 9, the form of the temperature change curve varies depending on the phase of the cardiac cycle. The thermal curves resulting vary due to their position in the cardiac cycle.

[0065] The series of coronary measurements demonstrate variations in the thermal response curve with the cardiac cycle. In contrast, experimental observation with previous systems using thermodilution via bolus injections did not see fluctuations in thermal transit times dependent on timing of bolus injections. These saline injections typically have to transit the entire coronary artery to the point of thermal measurement. This can mean that the cold saline may take at least one cardiac cycle in duration from injection to sensing, with any cyclical variation completely averaged out over the passage of fluid through the coronary artery.

[0066] Figure 10 is a schematic graph showing different pieces of data that may be measured from the temperature change curve. As indicated in Figure 10, the sensor apparatus 10 may be configured to measure one or more of the start time 11, the maximum upstroke 12 (time of maximum gradient), the time to peak 13 (the time taken to reach the maximum temperature change), the peak temperature change 14 (the maximum temperature change recorded), the maximum downstroke 15 (the time of the minimum gradient), and the run-off time 16 (the time axis intercept of the minimum gradient). Other metrics that may be measured comprise the start time (the time axis intercept of the maximum gradient), the plateau length, the area under the curve and a weighted average of the transit time (i.e. a weighted sum of the temperature change).

[0067] In other words, multiple points of the thermal curves are analysable, and curves may be filtered and fiducial points on the curves identified. The controller may be configured to make corrections to the curves may be made to account for errors inherent in the measurement system. Experimental and theoretical data imply that the measured transit time is dependent principally on the velocity of the fluid passing the thermal tagging diffuser. It may be assumed that a time-of-flight calculation can be made, using the distance between the thermal tagging diffuser 123 and temperature sensor 100 as a fixed distance, and the time between pulse being applied and a temperature rise indicating the time.

[0068] Multiple timepoints on the curve can be identified and used with a priori knowledge to determine exact (or pseudo-exact) transit timepoints. For example, a smoothed curve can have the inflection point above baseline, the maximal temperature rise time, the peak temperature, 25% peak rise etc times identified, and each of these will represent a slightly different part of the flow measurement. With multiple measurements, the controller can identify a plurality of fiducial points, representing time-of-flight across the entire cardiac cycle.

[0069] The controller may be configured to create a model of the flow in the vessel that would lead to the observed results. This may be achieved by using time of flight data to provide a velocity, which can be corrected using the known properties of blood flow around the device to provide and accurate flow velocity. The controller may be configured to perform calculations to differentiate flow across different parts of the heart cycle, and to construct a distribution of flow velocities across the cardiac cycle.

[0070] The controller may be configured to average results from a plurality of measurement. This may lead to higher fidelity. For example, the controller may control the thermal conditioner 120 to apply multiple pulses at the same point within the cardiac cycle e.g. by gating to the electrocardiogram.

[0071] The controller may use the instantaneous pressure measured from the sensor 100 in calculations of the flow, and of the instantaneous flow, to provide averaged or dynamic measures of the cardiac resistance.

[0072] Figure 11 is a graph showing the relationship between the phase of the cardiac cycle and the time to the maximum upstroke (blue plot), the time to peak (red plot) and the time to maximum down stroke (yellow plot). In Figure 11, the phase of the cardiac cycle is from the upstroke in pressure. Figure 11 shows parameters of the temperature change curve varying throughout the cardiac cycle.

[0073] The sensor apparatus 10 may make it possible to make an assessment of how the flow of the fluid varies within the cardiac cycle. The timing of the thermal conditioning may be based on a cardiac signal. The cardiac signal may comprise an electrocardiogram signal, for example. Alternatively, the cardiac signal may comprise a pressure signal. It may be preferred to use an electrocardiogram signal as the cardiac signal. This is because the pressure signal may be measured by the sensor apparatus 10. If the pressure changes, then the gating of the thermal tagging may vary undesirably. In contrast, the gating is less likely to vary when using an electrocardiogram signal as the cardiac signal on which the timing of the thermal conditioning of the fluid is based. The electrocardiogram signal is more independent than the pressure signal for controlling the timing of the thermal tagging.

[0074] The controller may be configured to compare data from the temperature sensor 100 between different points within the cardiac cycle. For example, the fluid flow rate may be compared in systole compared to diastole. This can help to differentiate between different types of cardiovascular disease. Based on such a comparison, it may be possible to select different drugs for treating the microvascular disease. Meanwhile, it may be possible to determine that there is a microvascular disease by gating the thermal tagging to a single point within the cardiac cycle. The controller may be configured to identify phases of flow within the vessel from the acquired variations in thermal transit times through the cardiac cycle. The controller is configured to analyse simultaneously acquired pressure signals using the identified phases of flow. The phase of pressure differential corresponding to the end of diastole can be estimated from the signals and used to perform a non-hyperaemic trans-lesion pressure measurement, which can provide data regarding impact of a lesion stenosis on blood flow acquired simultaneously with data on downstream run-off (downstream microvascular resistance).

[0075] Diastolic flow during hyperaemia is a measure of passive downstream flow, because in this state arterioles are maximally dilated and the motive force for blood flow in the coronary artery is the pressure differential on either side of the myocardium. The controller is configured to identify diastole from the electrocardiogram waveform and to trigger thermal tagging to be in the diastolic period. This can allow high-fidelity measurements to be made including signal averaging during bolus adenosine (or other hyperaemic agent) injection. The time-course of the changes in flow dynamics after an adenosine bolus provides a measure of the microvascular responsiveness and recovery.

[0076] The controller may be configured to select the point in the cardiac cycle corresponding to a highest fluid flow or a lowest fluid flow among the different points. For example, thermal tagging may be performed at a plurality of different phases of the cardiac cycle. The controller may be configured to compare the output of the temperature sensor 100 for the different phase and to select the point (i.e. phase) corresponding to the highest fluid flow and / or the lowest fluid flow.

[0077] The controller may be configured to identify the highest flow phase and to compare the highest fluid flow phase between two different cardiac conditions. The different cardiac conditions may be a base line condition and a hyperaemia condition. By comparing the highest flow between the two different conditions, the accuracy of the comparison may be improved. By measuring the fluid flow at the highest flow phase, the signal may be clearer. It may be possible to reduce the number of times of repeating the measurement in order to get a sufficient clarity of signal.

[0078] The controller may determine at which point in the cardiac cycle there is a maximum fluid flow. The controller may be configured to only trigger thermal tagging during a specific portion of the cardiac cycle during both baseline and hyperaemia. This allows data on flow to be compared at the same point in the cardiac cycle for both baseline and hyperaemia without needing to perform thermal tagging across the entire cardiac cycle at the beginning of the procedure to provide the necessary data from which flow can be deciphered. A hyperaemic condition may be induced while repeating the measurements with the thermal conditioning gated at the maximum flow phase. The increase in flow due to the hyperaemic condition may be measured.

[0079] Figure 15 is a graph showing the relationship between time (x axis) and aortic pressure (y axis). Figure 16 is a graph showing the relationship between time (x axis) and coronary flow (y axis). The point of minimum flow and the point of maximum flow are indicated in Figure 16. The systolic period 151 and the diastolic period 152 are indicated in Figure 15 and Figure 16.

[0080] The controller may be configured to control the thermal conditioner 120 to thermally condition the fluid at the selected point in the cardiac cycle so as to compare results from the temperature sensor 100 at different cardiac conditions.

[0081] The sensor apparatus 10 may comprise a pressure sensor. The pressure sensor may be configured to measure a pressure of the fluid. For example, the temperature sensor 100 shown in Figure 2 may function as a pressure sensor.

[0082] The controller may be configured to control the pressure sensor to measure the pressure of the fluid at the selected point in the cardiac cycle. The controller may be configured to receive data from the temperature sensor 100 of the sensed thermally conditioned fluid, and to measure a parameter of the fluid based on the received data.

[0083] The sensor apparatus 10 may comprise a processor. The processor is configured to receive data from the temperature sensor 100 of the sensed thermally conditioned fluid. The processor may be configured to create a model or flow of the fluid based on data from the temperature sensor 100 of the thermally conditioned fluid.

[0084] A hyperaemic condition may be induced, for example using an adenosine drip. The sensor apparatus 10 may be configured to automatically detect local hyperaemia. For example, the controller may be configured to control the thermal conditioner 120 to thermally condition the fluid at a timing based on a hyperaemia signal indicative of a hyperaemia cardiac condition. This may streamline the comparison of parameters of the fluid between a hyperaemic condition and a base line condition. The comparison may be made automatically. The manual step of inducing hyperaemia may be avoided. This may help to provide more accurate and / or more reliable results.

[0085] The hyperaemia signal may comprise a temperature change measured by the temperature sensor 100. The change in temperature measured by the temperature sensor 100 may be indicative of a hyperaemic cardiac condition. When the hyperaemic condition is identified, the fluid may be thermally conditioned so as to measure one or more parameters of the fluid in the hyperaemic condition. The measurement may then be compared to a corresponding baseline measurement.

[0086] When the sensor apparatus 10 comprises a pressure sensor, the hyperaemia signal may comprise a pressure change measured by the pressure sensor. The change in pressure may be indicative of a hyperaemic cardiac condition.

[0087] The controller may be configured to compare hyperaemia data from the temperature sensor 100 corresponding to the thermal conditioning at the timing based on the hyperaemia signal to baseline data from the temperature sensor 100 corresponding to thermal conditioning at a different timing. The controller may be configured to synchronise timings at which the thermal conditioner 120 thermally conditions the fluid with the cardiac cycle such that the hyperaemia data and the baseline data correspond to the same point in the cardiac cycle. This may improve the validity of the comparison. The natural fluctuations in parameters (e.g. pressure and / or flow rate) within a cardiac cycle may be substantially removed from the comparison.

[0088] Figure 12 schematically depicts a workflow of automatic hyperaemia detection. In step 21, an electrocardiogram waveform may be input. The electrocardiogram waveform may be a cardiac signal on which timing of thermal tagging may be based. In step 22, a pressure waveform may be input. The pressure waveform may be an additional or an alternative cardiac signal on which the timing of the thermal tagging may be based. In step 23, the controller may be configured to identify one or more fiducials on the pressure waveform and / or the electrocardiogram waveform. The fiducials may be markers, for example the peak pressure flow or peak electric signal.

[0089] In step 24, thermal tagging may be triggered. The thermal conditioner 120 is controlled to thermally condition the fluid at timings. The timings may be random. The timings may be selected so as to correspond to different phases of the cardiac cycle. The timings may be based on the electrocardiogram waveform and / or the pressure waveform. The thermal tagging may be output at step 34 such that the timing of the thermal tagging relative to the stage of the cardiac cycle is recorded.

[0090] In step 25, the temperature sensor 100 is configured to detect temperature changes in the fluid. In step 26, the controller may be configured to modulate the thermal pulse dependent on the thermal signal detected by the temperature sensor 100. For example, the controller may be configured to increase the thermal pulse when the temperature change is too low. By increasing the thermal pulse, the temperature change may be increased for subsequent measurements. Alternatively, the thermal pulse may be reduced so as to save power when the detected temperature change signal is more than clear enough.

[0091] In step 27, the flow of the fluid may be analysed. For example, one or more parameters such as pressure, and flow rate may be measured based on the output of the temperature sensor 100. In step 28, the controller may be configured to detect diastolic flow in relation to the electrocardiogram based on the results of the analysis of the flow of the fluid in step 27.

[0092] In one implementation, the thermal tagging is gated to the electrocardiogram waveform such that the thermal tagging is performed during diastolic flow. The system is primed waiting to detect hyperaemia. The controller may be configured to detect local pressure changes indicating that hyperaemia has been initiated.

[0093] The system is primed to detect hyperaemia by observing a drop in temperature greater than 1°C as the bolus passes by the temperature sensor 100. The controller may identify a hyperaemic condition by measuring a pressure rate drop after the bolus is detected. Once one or both of these occurrences are observed, thermal tagging begins.

[0094] Thermal tagging may be triggered in step 29 coupled to the electrocardiogram and / or pressure waveforms. Thermal detection may be performed in step 30, with modulation of the flow through, for example, an adenosine injection in step 31. The controller may be configured to update the thermal tagging parameters such as power, pulse width and / or pulse count of the excitation light based on the measurements that are being collected during thermal tagging. This is to ensure the best possible signal while depositing the least amount of energy.

[0095] In step 32, the variation in flow may be analysed. In particular, the variation in flow before and after the adenosine injection may be compared. In step 33, flow ratios and diastolic flow indices may be calculated based on the analysis in step 32. The controller may be configured to stop thermal tagging once the pressure returns to its state before hyperaemia was induced to ensure that the data analysed is during hyperaemia.

[0096] In one implementation, the thermal tagging is gated to the electrocardiogram waveform such that the thermal tagging is performed during diastolic flow. The system is then primed waiting to detect hyperaemia. Hyperaemia may be detected by local pressure changes. Additionally or alternatively, temperature changes may be measured to indicate hyperaemia. For example, the adenosine injection that causes hyperaemia may cause such a temperature change.

[0097] The thermal conditioner 120 may be configured to thermally condition the fluid by outputting pulses. For example, pulses of excitation light may be used to heat the fluid. The controller may be configured to control the time between pulses and the length of the pulses.

[0098] During use of the sensor apparatus 10, the temperature sensor 100 may be heated by the pulses from the thermal condition 120. Between pulses, the temperature sensor 100 may cool due to heat transfer with the fluid flowing past the temperature sensor 100.

[0099] The controller may be configured to receive a temperature signal from the temperature sensor 100. The temperature signal is indicative of self-heating, i.e. heating of the temperature sensor 100 by the pulses of interrogation light to the temperature sensor 100. The temperature signal received by the controller from the temperature sensor 100 may be indicative of the cooling of the temperature sensor 100 due to the heat transfer with the fluid flowing past the temperature sensor 100.

[0100] The controller may be configured to measure a parameter of flow of the fluid based on the received temperature signal. The temperature sensor 100 may be heating and cooling periodically during use of the sensor apparatus 10. The temperature signal indicating this heating and cooling can be used as a continuous signal from which the flow of the fluid may be determined. The temperature signal may be substantially continuous.

[0101] Self-heating is the continuous temperature rise that occurs due to the interrogation light source being absorbed by the materials distal to the fibre tip. The first component is the coating 120 that is used for temperature sensing. The result is a gradual temperature increase being present in the temperature signal with a degree of superimposed cooling occurring as the fluid flows past. The second component is direct heating of the fluid surrounding the temperature sensor 100. The fluid temperature increases as the interrogation light is absorbed and then decreases as the fluid flows past it. Figure 13 is a graph showing the relationship between time (x axis) and temperature change (y axis) measured by the temperature sensor 100. At the midpoint in the time period, the flow rate of the fluid is doubled. Figure 14 is a graph showing the relationship between time (x axis) and pressure change (y axis) measured by the temperature sensor 100. At the midpoint in the time period, the flow rate of the fluid is doubled. Figure 13 and Figure 14 shows how the temperature signal and / or pressure signal indicative of self-heating of the temperature sensor 100 varies when the flow rate is doubled. The self-heating can be used to provide information about the flow of the fluid.

[0102] The amount of self-heating is dependent on the power of the interrogation light source 130 which can be controlled by the controller. The controller may be configured to derive a metric from the temperature signal to determine information about the cardiac cycle. Selfheating can be differentiated from other phenomena in the body by varying the power of the interrogation light source 130.

[0103] The controller may be configured to vary the level of power output by the interrogation light source 130. Increasing the power to the maximum amount possible will give the highest temperature variation that is dependent on the flow of the vessel. From that signal, the controller may be configured to extract information on the instantaneous flow in the vessel and how it varies with the cardiac cycle. The controller may be configured to measure the parameter of flow of the fluid based on monitoring a change of the temperature signal over the varying level of power output.

[0104] The temperature signal may be a weighted differential of the flow velocity past the temperature sensor 100. The controller may be configured to integrate the temperature signal so as to measure a flow dynamic past the temperature sensor. Varying the power of the interrogation light source 130 changes the light / energy delivery at the temperature sensor 100 and the change and rate of change in heating / cooling provides a calibration measure of the energy absorbed within the system.

[0105] The controller may determine the blood flow from the temperature signal, for example using equations adapted from classical hot-wire anemometry. Prior calibration can be performed to enable such heating / cooling dynamics to give a measure of the overall flow past the temperature sensor 100. A further calibration can be made using thermal tagging, where thermal tagging provides a measure of vessel flow. Once the baseline calibration has been established, the dynamic temperature signal varying with the heartbeat can then take over as the primary instantaneous flow signal, providing a dynamic measure of beat-to-beat flow.

[0106] By using a combination of thermal tagging for calibration and the thermal anemometry approach to determine dynamics, the dependence on positioning of the microcatheter within the vessel is reduced and the entire cardiac cycle is covered. Furthermore, the interrogation light source 130 can be programmed to operate in a similar way to the excitation light source 121 where it generates pulses and the resulting temperature signal can be used to understand the dynamic temperature behaviour of the sensor in that specific instance.

[0107] Optionally, the average flow at baseline is obtained from thermal tagging data. The variance of flow within the cardiac cycle can be determined from the self-heating portion of the signal, obtained without thermal tagging. If the signal is overly noisy, this can be signal averaged as gated to the electrocardiogram. Bolus injection of a hyperaemic agent is detected by from a temperature drop caused by the injected hyperaemic agent, and this sets the system to monitor for a change in flow. A further check may be performed where the system waits for the pressure to drop to indicate that the system is in hyperaemia. The signal during that time period is recorded and we can calculate how the flow has changed by analysing the selfheating portion of the signal. The temperature rise is smaller because there is less time to heat up the surrounding fluid before it flows past the temperature sensor 100. The temperature increase and energy added are known, such that the hyperaemic flow can be calculated. As this is a dynamic measurement, the maximal hyperaemic flow can be determined as the maximal flow within a period of time (e.g. one minute following hyperaemia induction). This maximal hyperaemic flow can be used to form a flow ratio (Coronary Flow Reserve) or in the calculation of indices (Index of Mi crovascular Resistance).

[0108] Optionally, the controller is configured to receive a temperature signal from the temperature sensor 100. The temperature signal may comprise measurements made by the temperature sensor 100. The controller may be configured to control a level of the thermal conditioning by the thermal conditioner 120. For example, the controller may be configured to increase or decrease the level of thermal conditioning. Increasing the level of thermal conditioning may be increasing the power output by the diffuser 123, for example by increasing the length of pulses of excitation light or reducing the time between the pulses. Decreasing the level of thermal conditioning may mean reducing the power output by the thermal conditioner 120, for example by reducing the length of the pulses and / or increasing the time between pulses of excitation light.

[0109] The controller may be configured to control the level of thermal conditioning by the thermal conditioner 120 such that the received temperature signal from the temperature sensor 100 is substantially constant. The controller may be configured to measure a parameter of the fluid over time based on the level of thermal conditioning by the thermal conditioner 120 over time. The excitation light may be modulated to keep the temperature at the temperature sensor 100 substantially constant as the flow rate of the fluid changes. This may lead to more accurate measurement of the flow rate of the fluid.

[0110] The controller may be configured to control the thermal conditioner 120 to have an output having a periodicity. For example, the thermal conditioner 120 may output pulses for heating the fluid. The controller may be configured to receive a temperature signal from the temperature sensor 100 and to measure a parameter of the fluid over time by resolving the periodicity of the output of the thermal conditioner from the received temperature signal.

[0111] Figure 17 is a graph showing the relationship between time (x axis) and temperature change (y axis) during continuous use of the sensor apparatus 10. Looking at the temperature signal of the sensor, regions of warming 161 and cooling 162 can be identified. These regions of self-heating and cooling can be related back to periods of high and low flow. By performing thermal tagging within the low flow period, a “no flow / resting” metric can be measured. By performing thermal tagging within the high flow period, a “max flow” metric can be measured.

[0112] The averaged gated temperature curve, gated using the cardiac signal, provides a measure of phases of the cardiac cycle (e.g. diastole). The peak temperature corresponds to slowest flow within the cardiac cycle (i.e. warming is greatest, this is the flow-free period) and therefore diastole and a flow-free period. Selection of a time period around this period for can be used for pressure measurement corresponding to a diastolic index of pressure.

[0113] As shown in Figure 1, the sensor apparatus may comprise a guidewire 160. The thermal conditioner 120 may be on the guidewire 160. The temperature sensor 100 may be on the guidewire 160.

[0114] The sensor apparatus 10 may be configured such that the distance along the guidewire 160 between the thermal conditioner 120 and the temperature sensor 100 is adjustable. For example, the temperature sensor 100 may be fixed relative to the guidewire 160. The thermal conditioner 120 may be slidable along the guidewire 160. It may be that only a part of the thermal conditioner 120 is slidable along the guidewire 160. For example, the diffuser 123 of the thermal conditioner 120 may be movable along the guidewire 160. By moving the diffuse 123 along the guidewire 160, the distance between the diffuser 123 and the temperature sensor 100 may be varied.

[0115] In an alternative arrangement, the thermal conditioner 120 may be fixed relative to the guidewire 160. The temperature sensor 100 may be slidable along the guidewire 160. By sliding the temperature sensor 100 along the guidewire 160, the distance between the thermal conditioner 120 and the temperature sensor 100 may be varied.

[0116] In a further alternative, both the temperature sensor 100 and the thermal conditioner 120 may be slidable along the guidewire. One of the temperature sensor 100 and the diffuser 123 may be held stationary relative to the guidewire 160 while the other of the diffuser 123 and the temperature sensor 100 is moved relative to the guidewire 160. Accordingly, the distance between the temperature sensor 100 and the diffuser 123 of the thermal conditioner 120 may be varied.

[0117] The controller may be configured to control timing at which the thermal conditioner 120 thermally conditions the fluid and to adjust the distance between the thermal conditioner 120 and the temperature sensor 100. For example, the controller may be configured to control the thermal conditioner 120 to repeatedly thermally condition the fluid while the distance between the thermal conditioner 120 and the temperature sensor 100 is adjusted. Accordingly, multiple measurements of one or more parameters of the fluid may be made while the distance is increased or decreased.

[0118] The controller may be configured to control the thermal conditioner 120 to thermally condition the fluid at a timing based on a cardiac signal indicative of a cardiac cycle. For example, the repeated measurements may be made such that they are made at substantially the same phase within the cardiac cycle. The effect of the phase of the cardiac cycle on the measurement results may be substantially reduced. The measurements made at different distances between the thermal conditioner 120 and the temperature sensor 100 may be analysed to determine the effect of the distance on the measurements.

[0119] The controller may be configured to control the sensor apparatus 10 such that thermal tagging is performed at varying points along a vessel with the temperature sensor 100 remaining in place, or vice versa. Initial measurements may be taken with both the diffuser 123 and sensor 100 within the distal vessel. The diffuser 123 is then withdrawn whilst thermal tagging is underway. The temperature sensor acquires signals from thermal tagging throughout the vessel. Thereafter the diffuser 123 can be held within the proximal vessel and the temperature sensor 100 is withdrawn. This results in two separate but complementary series of measurements along the vessel, one due to the movement of the thermal tagging element (i.e. the diffuser 123) and the other due to the changes in the position of the temperature sensor 100.

[0120] As mentioned elsewhere, the controller may control the timings of thermally conditioning the fluid based on the cardiac cycle. This may improve the sensitivity to changes in flow dynamics along the vessel. Integrating these data with respect to the tracked position of the temperature sensor 100 or diffuser 123 within the vessel of interest allows a measure of the influence of bifurcation or side branch element on the flow dynamics within the vessel.

[0121] The controller may be configured to control the thermal conditioner 120 based on a signal-to-noise ratio (SNR) of a temperature signal from the temperature sensor 100. For example, if the temperature signal is determined to be relatively noisy, for example a particularly small signal, then the number of pulses of excitation light for thermally conditioning the fluid may be reduced. By reducing the number of pulses, the SNR may be improved.

[0122] Live analysis of the temperature signal and response to thermal tagging can be used to determine a quality measure (e.g. the SNR) and the use of the outputs of this analysis, along with electrocardiogram and pressure data, may specify the number and the nature of the pulses to obtain subsequently (e.g. if SNR is low, go ahead and acquire more pulses, or increase intensity of corresponding pulses within a safe limit, or increase duration, etc.).

[0123] Optionally, machine learning is used to determine the adjustment of any varying parameters for triggering or interpretation of sensing. For example, in an embodiment the controller is configured to use machine learning to determine the electrocardiogram or pressure waveform for triggering thermal tagging. In an embodiment the controller is configured to use machine learning to determine the electrocardiogram waveform to trigger thermal tagging to be in the diastolic period. In an embodiment the controller is configured to use machine learning to determine a specific portion of the cardiac cycle during both baseline and hyperaemia to trigger thermal tagging. In conclusion, various implementations have been described herein, by way of example only, and without limitation. It will be appreciated by the skilled person that features of different implementations can generally be combined with one another to create new implementations. Accordingly, the scope of the application is not restricted to particular examples or implementations described herein, but rather is defined by the appended claims and equivalents.

Claims

Claims1. A sensor apparatus comprising: a thermal conditioner configured to thermally condition a fluid; a temperature sensor configured to sense the thermally conditioned fluid; and a controller configured to control the thermal conditioner to thermally condition the fluid at a timing based on a cardiac signal indicative of a cardiac cycle, wherein the controller is configured to control the thermal conditioner based on the cardiac signal to thermally condition the fluid at different points in the cardiac cycle, wherein the controller is configured to compare data from the temperature sensor between the different points.

2. The sensor apparatus of claim 1, wherein the controller is configured to synchronise timings at which the thermal conditioner thermally conditions the fluid with the cardiac cycle.3.The sensor apparatus of claim 1 or 2, wherein the controller is configured to select the point in the cardiac cycle corresponding to a highest fluid flow or a lowest fluid flow among the different points.

4. The sensor apparatus of claim 3, wherein the controller is configured to control the thermal conditioner to thermally condition the fluid at the selected point in the cardiac cycle so as to compare results from the temperature sensor at different cardiac conditions.

5. The sensor apparatus of claim 3 or 4, comprising a pressure sensor configured to measure a pressure of the fluid, wherein the controller is configured to control the pressure sensor to measure the pressure of the fluid at the selected point in the cardiac cycle.

6. The sensor apparatus of any preceding claim, wherein the cardiac signal comprises a fluid pressure signal.

247. The sensor apparatus of any preceding claim, wherein the cardiac signal comprises an electrocardiogram signal.

8. The sensor apparatus of any preceding claim, wherein the controller is configured to receive data from the temperature sensor of the sensed thermally conditioned fluid, and to measure a parameter of the fluid based on the received data.

9. The sensor apparatus of any preceding claim comprising: a processor configured to receive data from the temperature sensor of the sensed thermally conditioned fluid, and to create a model of flow of the fluid based on data from the temperature sensor of the sensed thermally conditioned fluid.

10. A sensor apparatus comprising: a thermal conditioner configured to thermally condition fluid; a temperature sensor configured to sense the thermally conditioned fluid; and a controller configured to control the thermal conditioner to thermally condition the fluid at a timing based on a hyperaemia signal indicative of a hyperaemic cardiac condition.

11. The sensor apparatus of claim 10, wherein the hyperaemia signal comprises a temperature change measured by the temperature sensor.

12. The sensor apparatus of claim 10 or 11 comprising: a pressure sensor configured to measure a pressure of the fluid, wherein the hyperaemia signal comprises a pressure change measured by the pressure sensor.

13. The sensor apparatus of any of claims 10-12, wherein the controller is configured to compare hyperaemia data from the temperature sensor corresponding to the thermal conditioning at the timing based on the hyperaemia signal to baseline data from the temperature sensor corresponding to thermal conditioning at a different timing.

14. The sensor apparatus of claim 13, wherein the controller is configured to synchronise timings at which the thermal conditioner thermally conditions the fluid with the cardiac cyclesuch that the hyperaemia data and the baseline data correspond to the same point in the cardiac cycle.

15. A sensor apparatus comprising: a thermal conditioner configured to thermally condition a fluid by outputting pulses; a temperature sensor configured to measure a temperature of the thermally conditioned fluid; an interrogation light source configured to output interrogation light to the temperature sensor to measure a temperature of the thermally conditioned fluid; and a controller configured to receive a temperature signal from the temperature sensor indicative of heating of the temperature sensor by the pulses from the interrogation light source and cooling of the temperature sensor due to heat transfer with the fluid flowing past the temperature sensor, and to measure a parameter of flow of the fluid based on the received temperature signal.

16. The sensor apparatus of claim 15, wherein the temperature signal is substantially continuous.

17. The sensor apparatus of claim 15 or 16, wherein the controller is configured to vary a level of power output by the interrogation light source, and to measure the parameter based on monitoring a change of the temperature signal over the varying level of power output.

18. A sensor apparatus comprising: a thermal conditioner configured to thermally condition a fluid; a temperature sensor configured to measure a temperature of the thermally conditioned fluid; and a controller configured to receive a temperature signal from the temperature sensor, to control a level of thermal conditioning by the thermal conditioner such that the received temperature signal is substantially constant, and to measure a parameter of the fluid over time based on the level of thermal conditioning by the thermal conditioner over time.

19. A sensor apparatus comprising: a thermal conditioner configured to thermally condition a fluid; a temperature sensor configured to measure a temperature of the thermally conditioned fluid; and a controller configured to control the thermal conditioner to have an output having a periodicity, to receive a temperature signal from the temperature sensor and to measure a parameter of the fluid over time by resolving the periodicity of the output of the thermal conditioner from the received temperature signal.

20. A sensor apparatus comprising: a guidewire; a thermal conditioner on the guidewire configured to thermally condition a fluid; and a temperature sensor on the guidewire configured to sense the thermally conditioned fluid; wherein the sensor apparatus is configured such that a distance along the guidewire between the thermal conditioner and the temperature sensor is adjustable.

21. The sensor apparatus of claim 20, wherein the temperature sensor is fixed relative to the guidewire.

22. The sensor apparatus of claim 20 or 21, wherein the thermal conditioner is slidable along the guidewire.

23. The sensor apparatus of any of claims 20-22 comprising: a controller configured to control timing at which the thermal conditioner thermally conditions the fluid and to adjust the distance between the thermal conditioner and the temperature sensor.

24. The sensor apparatus of claim 23, wherein the controller is configured to control the thermal conditioner to repeatedly thermally condition the fluid while the distance between the thermal conditioner and the temperature sensor is adjusted.

25. The sensor apparatus of claim 23 or 24, wherein the controller configured to control the thermal conditioner to thermally condition the fluid at a timing based on a cardiac signal indicative of a cardiac cycle.

26. The sensor apparatus of any of claims 1-19 and 23-25, wherein the controller is configured to control the thermal conditioner based on a signal-to-noise ratio of a temperature signal from the temperature sensor.

27. The sensor apparatus of any of claims 1-19 and 23-26, wherein the controller is configured to control a duration, frequency and / or intensity of pulses output by the thermal conditioner for thermal conditioning based on characteristics of a cardiac signal indicative of a cardiac cycle.

28. The sensor apparatus of any of claims 1-19 and 23-27, wherein the controller is configured to filter a temperature signal from the temperature sensor based on a cardiac signal indicative of a cardiac cycle.

29. The sensor apparatus of any of claims 1-19 and 23-28, wherein the controller is configured to control the thermal conditioner based on a breathing signal indicative of a breathing cycle.

30. The sensor apparatus of any of claims 1-19 and 23-29, wherein the controller is configured to control the thermal conditioner based on a location signal indicative of a location of the thermal conditioner and / or the temperature sensor.

31. The sensor apparatus of any of claims 1-19 and 23-30, wherein the controller is configured to deconvolve a temperature signal from the temperature sensor based on a known duration of a pulse output by the thermal conditioner.

32. The sensor apparatus of any preceding claim, wherein: the thermal conditioner is configured to thermally tag the fluid; the temperature sensor is configured to sense the thermally tagged fluid; andthe controller is configured to measure a flow of the fluid based on a time difference between the thermal tagging and the sensing of the thermally tagged fluid.

33. The sensor apparatus of any preceding claim, wherein the thermal conditioner is configured to thermally condition the fluid by outputting radiation to the fluid.

34. The sensor apparatus of any preceding claim, wherein the thermal conditioner comprises an excitation light guide configured to transmit excitation light for thermally conditioning the fluid.29

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