Method and system for depth-dependent measurements of dynamic properties

Abstract

The invention provides a method for determining a material property of a sample (50) using a photoelectric detector (120), wherein the photoelectric detector (120) has a frame rate RD and comprises an array (122) comprising n pixels (125), wherein the frame rate RD ≥ 10 kHz, wherein n ≥100, and wherein the method comprises: providing measurement radiation (111) along a measurement path (10) and along a reference path (20), wherein the measurement radiation (111) is coherent, wherein the measurement radiation (111) comprises m measurement phases (40), wherein m ≥ 2, wherein the measurement phases (40) have a measurement duration (Tm), wherein RD*Tm≥ 100, wherein each measurement phase (40) comprises a frequency sweep (45) over a frequency range selected from the range of 10 - 1000 GHz, wherein the measurement path (10) enters the sample (50) at an entrance location (51), passes through at least part of the sample (50), and exits the sample (50) at an exit location (52), wherein the entrance location (51) and the exit location (52) are separated by at most 5 cm, wherein the measurement path (10) downstream of the sample (50) differs from the measurement path (10) upstream of the sample (50), and wherein the measurement path (10) and the reference path (20) merge into a combined path (30) downstream of the sample (50); detecting a spectral interference pattern of the measurement radiation (111) travelling along the combined path (30) using the photoelectric detector (120) to provide a spectral signal (Sm,n) for each of the m measurement phases (40) and the n pixels (125); and determining the material property based on the spectral signals (Sm,n).

Description

[0001] Method and system for depth-dependent measurements of dynamic properties

[0002] FIELD OF THE INVENTION

[0003] The invention relates to a method for determining a material property of a sample. The invention further relates to a system for determining a material property of a sample.

[0004] BACKGROUND OF THE INVENTION

[0005] Methods for determining material properties of samples are known in the art. For instance, WO2015189174A2 describes systems and methods for interferometric imaging, including a partial field frequency-domain interferometric imaging system in which a light beam is scanned in two directions across a sample and the light scattered from the object is collected using a spatially resolved detector. The light beam could illuminate a spot, a line or a two-dimensional area on the sample.

[0006] US11060843B2 describes that source light having a range of optical wavelengths is split into sample light and reference light. The sample light is delivered into a sample, such that the sample light is scattered by the sample, resulting in signal light that exits the sample. The signal light and the reference light are combined into an interference light pattern having optical modes having oscillation frequency components respectively corresponding to optical pathlengths extending through the sample. Different sets of the optical modes of the interference light pattern are respectively detected, and high-bandwidth analog signals representative of the optical modes of the interference light pattern are output. The high-bandwidth analog signals are parallel processed, and mid-bandwidth digital signals are output. The mid-bandwidth digital signals are processed over an i number of iterations, and a plurality of low-bandwidth digital signals are output on the ith iteration. The sample is analyzed based on the low-bandwidth digital signals.

[0007] STRANGMAN G. E. et al., Depth Sensitivity and Source-Detector Separations for Near Infrared Spectroscopy Based on the Colin27 Brain Template, PLOS ONE, 2013, describes the use of Monte Carlo simulations to evaluate (i) the spatial sensitivity profile of near-infrared spectroscopy (NIRS) to brain tissue as a function of source-detector separation, (ii) the NIRS sensitivity to brain tissue as a function of depth in this realistic and complex head model, and (iii) the effect of NIRS instrument sensitivity on detecting brain activation. WO2024172654 describes a method for determining a material property of a sample, wherein the method comprises: i) a measurement stage comprising providing measurement radiation along a measurement path and along a reference path, wherein the measurement radiation has a spectral distribution comprising a plurality of distinct peaks in the wavelength range of 5 - 5000 nm, and wherein the measurement radiation is coherent, and wherein the measurement path passes through at least part of the sample and wherein the measurement path and the reference path merge into a combined path; ii) a detection stage comprising (a) detecting a spectral interference pattern of combined radiation travelling along the combined path and (b) providing a related spectral signal; and iii) an analysis stage comprising determining the material property based on the related spectral signal.

[0008] KONG et al., Long-term laser frequency stabilization using fiber interferometers, Review of Scientific Instruments, 2015, vol. 86, describes long-term laser frequency stabilization using only the target laser and a pair of 5 m fiber interferometers, one as a frequency reference and the second as a sensitive thermometer to stabilize the frequency reference.

[0009] SUMMARY OF THE INVENTION

[0010] Flow, such as blood flow, may be an important biomarker in physiology and for diagnosis.

[0011] The prior art may describe several methods to determine blood flow. For instance, Laser Doppler Flowmetry (LDF) and Laser Doppler Holography (LDH) involve measuring a Doppler shift from dynamic scatters (e.g. red blood cells) to determine flow rate, whereas laser speckle contrast imaging (LSCI) measures the spatial or temporal contrast of speckle to reconstruct an image visualizing flow. However, both techniques are limited to measuring flow in deep tissue, moreover, the presence of any superficial flow may contaminate the measurement of deep flow. The prior art may further describe the use of large sourcedetector (SD) separation for LDF and LSCI to address these limitations by collecting predominantly multiple-scattered photons for deeper tissue flow measurements. However, as photon throughput may decrease exponentially with increasing SD separation, such approaches may detrimentally affect signal-to-noise ratio and overall effectiveness in measuring deep tissue blood flow.

[0012] Diffuse correlation spectroscopy (DCS) may involve the use of large sourcedetector (SD) separation (-1-3.5 cm) to focus on deep flow but may suffer from low spatial resolution (related to the SD separation) and low photon throughput, and may therefore rely heavily on single-photon measurement detectors, which may be sensitive to ambient light and relatively expensive.

[0013] The prior art may further describe interferometric approaches. These approaches may take advantage of heterodyne gain to boost weakly scattered photons to determine the blood flow index (BFi) without the single photon counting detector. Specifically, interferometric near-infrared spectroscopy (iNIRS) and dual-comb diffusing-wave spectroscopy (DC-DWS) may typically use Mach-Zehnder interferometers to measure the distribution of photon time-of-flight (DTOF) of scattered photons to determine optical properties of tissue and to determine depth-dependent or TOF-dependent blood flow by repeating the measurement. However, these methods may suffer from low photon throughput and low signal -to-noise (SNR) ratios. Interferometric diffusing-wave spectroscopy (iDWS) may involve the use of a single-wavelength laser, multimode fiber (MMF) collection, and a relatively fast CMOS camera to achieve parallel DWS detection. Similarly, interferometric speckle visibility spectroscopy (iSVS) may be similar regarding laser and MMF collection, but may use a relatively low-frame rate camera to calculate the speckle visibility to determine the blood flow. These latter two methods may achieve substantially higher SNR than single detector schemes but are not suitable for measuring optical properties and depth-dependent dynamics.

[0014] The prior art may further describe Frequency-Modulated Light Scattering (FMLS). FMLS may utilize multimode fibers to collect photons and measure a Doppler-broadened distribution of time-of-flight (DTOF), achieving high photon throughput. However, challenges in effective detection of the high photon throughput mat lead to a relatively low signal-to-noise ratio (SNR).

[0015] The prior art may further describe a combination of iDWS with a TOFs gate where the laser frequency scans rapidly during a camera exposure time to create arbitrary effective linewidth to interfere with photons within the coherent gate. However, this approach may involve complicated data processing and may also not be suitable for simultaneously measuring optic properties and depth-dependent dynamics.

[0016] The prior art may further describe Optical Coherence Tomography (OCT) approaches. In traditional OCT, interference may be measured between (a) light that passed through a sample and (b) reference light having a matching optical pathlength (and not passing through the sample). To measure at different depths in the sample, a length of the reference optical pathlength may be adjusted by moving components. In swept-source (SS)-OCT, such moving is avoided by sweeping a source light wavelength. As SS-OCT uses directly reflected radiation, only low depth can be measured. Also, the size of the wavelength range used may affect a depth resolution. In particular, a larger wavelength range may provide a higher depth resolution. On the other hand, a larger wavelength range may result in a larger scanning time, which in turn may result in a lower sampling rate. Further, OCT-based approaches may be directed to the detection of single-scattered photons, which may be limited to shallow measuring as, at larger depths, measurement radiation is more likely to be scattered multiple times. As such, methods based on measurement radiation scattered once within the sample may not be suitable for detecting signals from larger depths where multiple-scattered photons dominate over single-scattered photons.

[0017] The prior art may further describe approaches

[0018] Hence, it is an aspect of the invention to provide an alternative method and system for determining a material property of a sample, which preferably further at least partly obviate one or more of above-described drawbacks. The present invention may have as object to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.

[0019] In a first aspect, the invention provides a method for determining a material property of a sample using a photoelectric detector. The photoelectric detector may have a frame rate RD, especially wherein the frame rate RD > 10 kHz. The photoelectric detector may comprise an array of n pixels, especially wherein n> 100. The method may especially comprise providing measurement radiation along a measurement path and along a reference path, especially wherein a (first) beam splitter is configured to split the measurement radiation over the measurement path and the reference path. The measurement radiation may especially be coherent. Further, the measurement radiation may comprise m measurement phases, especially wherein m > 2, i.e., the method may comprise providing the measurement radiation with m measurement phases, especially wherein m > 2. In embodiments, the measurement phases may have a (same) measurement duration (Tm), especially wherein Ro*Tm > 100. In other words, the measurement duration (Tm) may be selected such that the photoelectric detector can provide at least 100 frames for each measurement phase. Further, in embodiments, each measurement phase may comprise a (same) frequency sweep over a frequency range (wherein the smallest frequency and the largest frequency of the frequency range may be individually) selected from the range of 10 - 1000 GHz, such as from the range of 10 - 100 GHz. In embodiments, the measurement path may enter the sample at an entrance location (or ‘sample entrance location’), pass through at least part of the sample, and exit the sample at an exit location (or ‘sample exit location’), especially wherein the entrance location and the exit location are separated by at most 5 cm. The measurement path downstream of the sample may especially differ from the measurement path upstream of the sample, i.e., the exit location may differ from the entrance location and / or the measurement path may exit the sample at a different angle than at which it enters the sample. The measurement path and the reference path may especially merge into a combined path downstream of the sample. In particular, the merging of the measurement path and the reference path may cause interference of the (combined) measurement radiation along the combined path. The method may further comprise detecting a spectral interference pattern of the (combined) measurement radiation travelling along the combined path using the photoelectric detector, especially thereby providing spectral signals (Sm,n) for each (combination) of the m measurement phases and the n pixels. In particular, if RD*TM equals 100, the method may provide 100 spectral signals (Sm,n) for each combination of the m measurement phases and the n pixels. The method may further comprise determining the material property based on the spectral signals (Sm,n).

[0020] In specific embodiments, the invention may provide a method for determining a material property of a sample using a photoelectric detector, wherein the photoelectric detector has a frame rate RD and comprises an array comprising n pixels, wherein the frame rate RD > 10 kHz, wherein n > 100, and wherein the method comprises: (i) providing measurement radiation along a measurement path and along a reference path, wherein the measurement radiation is coherent, wherein the measurement radiation comprises m measurement phases, wherein m > 2, wherein the measurement phases have a measurement duration (Tm), wherein Ro*Tm > 100, wherein each measurement phase comprises a frequency sweep over a frequency range selected from the range of 10 - 100 GHz, wherein the measurement path enters the sample at an entrance location, passes through at least part of the sample, and exits the sample at an exit location, wherein the entrance location and the exit location are separated by at most 5 cm, wherein the measurement path downstream of the sample differs from the measurement path upstream of the sample, and wherein the measurement path and the reference path merge into a combined path downstream of the sample; (ii) detecting a spectral interference pattern of the measurement radiation travelling along the combined path using the photoelectric detector to provide a spectral signal (Sm,n) for each of the m measurement phases and the n pixels; and (iii) determining the material property based on the spectral signals (Sm,n).

[0021] The method and system (see below) of the invention may facilitate simultaneously measuring optic properties and depth-dependent dynamics with a high Signal-to-Noise Ratio (SNR) by using a multiple-wavelength laser and a CMOS camera. This can overcome the prior art limitations mentioned above. Further, the system of the invention may be relatively economical in terms of hardware requirements.

[0022] In particular, the method of the invention may facilitate measuring dynamic properties in a material at different depths using an interferometrical setup. Specifically, the invention relates to the measuring of flow, e.g., of blood flow, at different depths using a photoelectric camera, e.g., a Complementary Metal Oxide Semiconductor camera (CMOS camera), with multipixel detection and a wavelength-swept laser source providing a frequency sweep. In particular, the rate of the frequency sweep may be selected in view of the frame rate of the photoelectric detector. Of note is that the rate of the frequency sweep may, in comparison to prior art approaches, be deliberately selected to be relatively low in order to facilitate the detection of the dynamics in the incident radiation by the photoelectric detector, i.e., the measurement period may be deliberately selected to be relatively large to facilitate the detection of the dynamics in the incident radiation. In particular, the relatively low frequency sweep rate and the detection using a multipixel photoelectric detector may facilitate obtaining a higher signal-to-noise ratio compared to prior art approaches. Further, the photoelectric detector, e.g., a CMOS camera, may be relatively cheap and simple in use compared to sensors used in prior art approaches. Hence, the method and system of the invention may provide an improved signal-to-noise ratio while being cheaper and less complex than existing solutions.

[0023] The method and system of the invention may provide an improved signal-to-noise ratio compared with other single-detector interferometric method, such as interferometric NIRS, dual-comb DWS, frequency-modulated light scattering due to: (1) photon detection using a high number of pixels; and (2) a time-of-flight (TOF) discrimination ability enabling low SD separation while maintaining high specificity for deep layers. Furthermore, the method and system of the invention may facilitate measuring optical properties and depth-dependent dynamics simultaneously.

[0024] Hence, in embodiments, the invention may provide a method for determining a material property of a sample. The term “material property” may herein refer to any property of a material, that may be measured by optical detection methods. In embodiments, the material property may comprise a dynamic material property. In embodiments, the material property may comprise one or more of a material composition, a flow velocity, a flow velocity profile, a reduced scattering coefficient of the sample, a rheological parameter, such as viscosity and / or elasticity, a temperature, an (average) absorption coefficient and a size of a particle undergoing Brownian motion. Especially, the material property may comprise a flow velocity, such as a blood flow velocity. The term “sample” may herein refer to an object comprising a material being measured in the method and system of the invention. In embodiments, the sample may comprise one or more of a wall, a floor, a ceiling, a road, a pipe, a tube, (a part of) an animal, such as (a part of) a human, like a limb, especially a head of an animal, more especially a brain of an animal. However, other samples may also be possible.

[0025] In embodiments, the sample may especially be a turbid sample. That is, the sample may be an opaque sample (such as e.g. in the case of a solid sample), and / or the sample may be a cloudy sample (such as e.g. in the case of a liquid sample). The turbidity of a sample may in embodiments be a measure of the intensity of light transmitted through the sample, and / or of the intensity of light scattered by the sample. In embodiments, the turbidity of the sample may be assessed with a nephelometer using the nephelometric method, wherein the turbidity is indicated in nephelometric turbidity units (NTUs). A nephelometer measures the intensity of light scattered by a sample and compares it to the intensity of light scattered by a reference standard (e.g. a formazin suspension in water with a known turbidity value), wherein the sample turbidity is proportional to the intensity of the scattered light. In embodiments, the sample may have a turbidity of > 100 NTU, such as > 250 NTU, especially > 500 NTU, like > 1000 NTU. Alternatively, the percentage of light transmitted through the sample may be used. That is, the turbidity of the sample may be determined by measuring the intensity of light transmitted through a sample, and dividing this by the intensity of light irradiating the sample. Assuming irradiation with the measurement radiation at an angle of irradiation of 90° to a surface of the sample, and a sample thickness of 1 cm, the sample may have an (average) turbidity of < 0.8, such as < 0.65, especially < 0.5, like < 0.25, wherein a turbidity of 0.5 indicates that half of the incident light is transmitted through the sample. Hence, in specific embodiments, the sample may be turbid. A turbid sample may provide the benefit that the measurement radiation may be scattered (multiple times) within the sample, before propagating to the (combined path and the) detector.

[0026] For explanatory purposes, the invention may herein especially be described in the context of a blood flow measurement. It will be clear to the person skilled in the art, however, that the invention is not limited to such embodiments and may, for instance, further relate to determining material properties of (inanimate) objects, such as for non-invasively determining (depth-dependent) flow rates in a pipe system.

[0027] The method may especially involve detection using a photoelectric detector (or ‘photoelectric sensor’). The term ‘photoelectric detector’ may herein especially refer to a detector configured to provide an electrical signal in response to detected radiation. The photoelectric detector may have a frame rate RD, i.e., the photoelectric detector may be configured to take (or “generate”) RD frames per second. The frame rate may especially be selected to be sufficiently high to acquire multiple images per measurement period, e.g., such that Ro*Tm> 100. In embodiments, RD may be selected from the range of > 1 kHz, such as from the range of > 5 kHz, especially from the range of > 10 kHz. In further embodiments, RD may be selected from the range of > 20 kHz, such as from the range of > 50 kHz, such as from the range of > 100 kHz, especially from the range of > 200 kHz. In particular, a high frame rate may be beneficial for the SNR. A high frame rate may, however, further result in a high signal bandwidth (or “high data throughput demand”) and may result in substantial power requirements, which may, for instance, result in a short battery life. In further embodiments, RD may be selected from the range of < 4 MHz, such as from the range of < 2 MHz, such as from the range of < 1 MHz, especially from the range of < 500 kHz. For instance, in embodiments, the frame rate RD may be selected from the range of 50 kHz - 4 MHz, such as from the range of 100 kHz - 2 MHz, especially from the range of 100 kHz - 1 MHz.

[0028] The photoelectric detector may further comprise an array, especially a ID array, or especially a 2D array, comprising n pixels. In embodiments, n > 10, such as n > 50, especially n > 100. In further embodiments, n > 500, such as n > 1000, especially n > 2000. In further embodiments n > 5000, such as n > 10000. In further embodiments, n < 10000000, such as n < 5000000, especially n < 2000000. In further embodiments, n < 1000000, such as n < 100000, especially n < 50000.

[0029] The resolution (total pixel number used) and frame rate of (commercially available) photoelectric detectors may have a reciprocal relationship. Hence, in embodiments, the photoelectric detector may be cropped, i.e., the number of pixels may be decreased to increase the frame rate RD. In particular, in embodiments, the photoelectric detector may have ntot total pixels, wherein a proper subset of the ntot total pixels is configured to detect the measurement radiation, wherein the proper subset comprises (such as consists of) the n pixels (see above).

[0030] As described above, the photoelectric detector may especially comprise a CMOS camera.

[0031] In further embodiments, the photoelectric detector may comprise a Charge-Coupled Device (CCD) camera.

[0032] The method may further comprise providing measurement radiation, especially using a radiation source (see below). The measurement radiation may especially comprise laser radiation. The measurement radiation may especially have a frequency (or wavelength) suitable for scattering in the sample. In particular, the measurement radiation may be scattered within the sample (while passing through the at least part of the sample). Especially, photons comprised by the measurement radiation may be scattered within the sample by particles (such as e.g. blood cells, proteins, granules, etc.) present in the (turbid) sample. In embodiments, the measurement radiation may generally (on average) be scattered multiple times within the sample. That is, the photons may (on average) deviate from their respective (straight) trajectories multiple times within the sample (while passing through the at least part of the sample). In embodiments, the measurement radiation, such as especially photons comprised by the measurement radiation, may (on average) be scattered > 2 times, such as > 5 times, especially > 10 times, like > 15 times, within the (turbid) sample. Additionally or alternatively, the measurement radiation, such as especially photons comprised by the measurement radiation, may (on average) be scattered < 1000 times, such as < 500 times, especially < 100 times, like < 50 times, within the (turbid) sample. Hence, in specific embodiments, the sample may be turbid, wherein the measurement radiation may be scattered multiple times within the sample. Multiple scattering of the measurement radiation may facilitate determining a reduced scattering coefficient (ps’) of the sample. Further, a method comprising determining a material property of a sample based on measurement radiation scattered multiple times within the sample may facilitate measuring at larger depths in the sample. That is, at larger depths, measurement radiation is more likely to be scattered multiple times.

[0033] The method may especially comprise providing the measurement radiation with m measurement phases, especially wherein m > 2, such as m > 3, especially m > 5, such as m > 10. In further embodiments, m > 20, such as m > 30, especially m > 50, such as m > 100. Especially, each measurement phase may comprise a (same) frequency sweep, especially over a frequency range selected from the range of 5 - 2000 GHz, such as from the range of 10 -1000 GHz, especially from the range of 10 - 100 GHz, such as from the range of 20 - 80 GHz.

[0034] The term “frequency sweep” may herein refer to a pattern of changing frequency (of radiation) over time. For instance, a frequency sweep may comprise a (linear) change from a first (smallest) frequency to a second (largest) frequency (or vice versa), wherein the first frequency and the second frequency are both selected from the frequency range. Similarly, a frequency sweep may comprise a (linear) change from a first (smallest) frequency to a second (largest) frequency and back. Hence, using a frequency sweep, the frequency of the measurement radiation may be (continuously) varied during the measurement phase, facilitating measuring at different sample depths in each measurement phase (as depth resolution may be frequency-dependent). In particular, each measurement phase may have a (same) measurement duration (Tm) and especially a same frequency sweep.

[0035] In embodiments wherein the frequency sweep comprises a linear change from a first frequency to a second frequency, the frequency sweep may have a sweep rate of |fi-f2| / Tm. In embodiments wherein the frequency sweep comprises a linear change from a first frequency to a second frequency and then back to the first frequency, the frequency sweep may have a sweep rate of 2*|fi-f2| / Tm, wherein the direction of change reverses halfway through the frequency sweep.

[0036] In embodiments, the frequency sweeps may especially have (essentially) the same pattern, i.e., the same first frequency, second frequency, and sweep rate (or “rate of change”). In further embodiments, each frequency sweep may comprise a monotonic increase of the frequency. In further embodiments, each frequency sweep may comprise a monotonic decrease of the frequency. Hence, in embodiments, the frequency sweep comprises a linear frequency sweep, e.g., with a / -shape or a \-shape. The frequency sweeps may thus have a ramp shape, which may facilitate providing linear frequency modulation. In further embodiments, each frequency sweep may comprise both increases and decreases in frequency. For instance, the frequency sweeps may be shaped according to a (sine) waveform or may have a A-shape. The frequency sweep may thus have a sinusoidal shape, which may reduce modulation noise but may imply additional non-linear post-processing. Hence, in embodiments, the frequency sweep may comprise a non-linear frequency sweep, such as a sine frequency sweep.

[0037] Hence, in embodiments, the frequency sweep may comprise (monotonically) sweeping from a first frequency (fi) to a second frequency (f2) and optionally back from the second frequency (f2) to the first frequency (fi). Especially, in such embodiments, fi and fi may differ by at least 5 GHz, such as by at least 10 GHz, especially by at least 20 GHz. In further embodiments, fi and fi may differ by at most 1000 GHz, such as by at most 900 GHz, especially by at most 500 GHz. In further embodiments, fi and fi may differ by at most 200 GHz, such as by at most 100 GHz, especially by at most 50 GHz.

[0038] As the swept frequency bandwidth may be relatively narrow, the sample may be considered to have (approximately) the same absorption and scattering coefficients for photons with different frequencies. The multiple-scattered photons with different paths may interfere with the reference beam continuously, resulting in different beat frequencies, which may be identified after Fourier transformation (see below). The continuous interference of photons from the measurement and reference path may benefit the SNR.

[0039] In further embodiments, each measurement phase may have a (same) measurement duration Tm. In particular, the frequency sweep in each measurement duration may have a (same) measurement duration Tm. The measurement duration may especially be selected to facilitate generating a substantial number of frames by the photoelectric detector during each measurement phase. In particular, in embodiments, the measurement duration Tmmay be selected such that Ro*Tm > 10, such as > 50, especially > 100. In further embodiments, the measurement duration Tmmay be selected such that Ro*Tm > 1000, such as > 2000, especially > 5000. In further embodiments, the measurement duration Tmmay be selected such that RD*Tm< 10000, such as < 5000, especially < 2000, such as < 1000.

[0040] For example, when RD*Tm= 100, the photoelectric detector may generate 100 images for each measurement phase (and for each pixel; see below). Although short measurement phases (small Tm) may be considered beneficial in view of picking up on fast sample dynamics, a large value of RD*Tm, which may be obtainable by selecting a long measurement duration Tm, may be beneficial in view of the SNR. In embodiments, the measurement duration Tmmay especially be selected such that Ro*Tm is selected from the range of 50 - 20000, such as from the range of 100 - 15000, especially from the range of 1000 -10000.

[0041] In particular, Tmmay be selected in view of the frame rate RD of the photoelectric detector, especially such that (fo+Af0pt / Tm*TOFmax) < RD, such as < RD / 2, especially < RD / 4. In particular, fo may be an initial beat frequency due to path length difference between the measurement path and the reference path, Afopt may be the difference between the lowest and the highest frequency in the frequency sweep, e.g., between the first frequency fi and the second frequency fi in the frequency sweep, and TOFmax may be the maximum photon time of flight (TOF) in the sample.

[0042] In further embodiments, Tm> 0.0001 s, such as > 0.001 s. In further embodiments, Tm> 0.01 s, such as > 0.1 s. In further embodiments, Tmis selected from the range of < 2 s, such as < 1 s, especially < 0.1 s. For instance, in embodiments, Tmmay be selected from the range of 0.001 - 1 s, especially from the range of 0.01 - 1 s. In particular, the measurement duration Tmmay be selected to be (substantially) smaller than the duration of an event to be measured, e.g., Tmmay be selected to be < 0.1 s for capturing flow changes due to a heart beat. Further, Tmmay be selected to be sufficiently large to facilitate acquiring a plurality of frames (using the photoelectric detector), e.g. at least 100 frames, within a measurement phase. In particular, a longer measurement duration Tmmay relieve frame rate requirements for the photoelectric detector, providing compatibility with a wider range of photoelectric detectors, e.g. with a camera having a relatively high resolution (also see above) and / or a low signal bandwidth.

[0043] Further, the measurement duration Tmmay be selected in view of a speckle decorrelation time Ta, especially wherein the speckle decorrelation time Ta is the smallest speckle decorrelation time Tain a (measured part of a) sample. In particular, in embodiments, Tm> Ta, such as > 10*Ta, especially > 100*Ta. In further embodiments, Tm / Ta may be selected from the range of 10 - 100000, such as from the range of 100 - 10000. The term “speckle decorrelation time” herein refers to the amount of time after which a (normalized) autocorrelation value of speckle intensity decays to less than half of its initial value. The speckle decorrelation time of a (to be measured part of a) sample may, for instance, be determined as described in QURESHI el al., In vivo study of optical speckle decorrelation time across depths in the mouse brain, Biomedical Optics Express, 2017, vol. 8, no. 11, which is hereby herein incorporated by reference.

[0044] In embodiments, the measurement radiation may be coherent. The term “coherent” may herein especially refer to radiation having a coherence length of at least two times a length of the measurement path, such as at least three times the length of the measurement path. In embodiments, the radiation may have a coherence length of at least 0.5 m, such as at least 1 m, especially at least 2 m. The term “coherence length” may herein refer to the maximum optical path difference at which the phase relationship of light radiation during propagation can be maintained sufficiently to keep the visibility of interference fringes at 50% in a Michelson interferometer.

[0045] The method may especially comprise providing the measurement radiation along a measurement path and along a reference path, i.e., the method may comprise providing (sample) measurement radiation along the measurement path and (reference) measurement radiation along the reference path. The measurement radiation provided to the measurement path and to the reference path may have (essentially) the same spectral distribution, i.e., the sample measurement radiation (upstream of the sample) and the reference measurement radiation may have (essentially) the same spectral distribution. The measurement radiation may for instance be split over the measurement path and the reference path by a beam splitter. Especially, the method may comprise providing (first) measurement radiation (or “sample measurement radiation”) along a measurement path. In embodiments, the measurement path may pass through at least part of the sample. In further embodiments, the method may comprise providing (second) measurement radiation (or “reference measurement radiation”) along a reference path. The reference path may in embodiments not pass through the sample. In further embodiments, the method may comprise providing measurement radiation along a measurement path and along a reference path. Especially, path lengths of the measurement path and the reference path may differ by at most 10 km, such as at most 1 km, especially at most 1 m. In embodiments, the path lengths of the measurement path and the reference path may differ 0 mm - 100 m, such as 0 mm - 20 m, especially 0 mm - 6m. In further embodiments, the path lengths of the measurement path and the reference path may differ 5 mm - 10 m, such as 1 cm - 7 m, especially 1 m - 6 m. In further embodiments, the measurement path and the reference path may have (essentially) the same path length.

[0046] For instance, in embodiments, the method may comprise providing measurement radiation to a beam splitter, wherein the beam splitter is configured to split the measurement radiation into (sample) measurement radiation along a measurement path and (reference) measurement radiation along a reference path.

[0047] The term “path”, such as in “measurement path” and “reference path” may herein especially refer to a course along which the measurement radiation travels. The path(s) may pass through one or more of air, optical elements, the sample (for the measurement path), and optical fibers.

[0048] The measurement path may especially be longer than the reference path. In particular, a length difference AL between the measurement path and the reference path may be selected such that an initial beat frequency fo, which does not include the scattering path, is about 0.1 *RD. The term “initial beat frequency” may herein refer to the beat frequency between (a) the measurement radiation traveling along the reference path and (b) the part of the measurement radiation that travels (predominantly) along the measurement path and is scattered at the surface of the sample. The initial beat frequency may be the minimum beat frequency and can be adjusted by tuning the length difference AL between the measurement path and the reference path. An initial beat frequency fo above RD / 2 may lead to aliasing errors in line with the Nyquist theorem, whereas an initial beat frequency fo close to 0 may lead to flicker noise. Hence, in embodiments, fo / Ro may be selected from the range of 0.001-1.5, such as from the range of 0.01-1, especially from the range of 0.05-0.2, such as about 0.1. In particular, values of fo around 0.1 *RD may be beneficial for the SNR.

[0049] In particular, the measurement path may enter the sample at an entrance location (or ‘sample entrance location’), pass through at least part of the sample, and exit the sample at an exit location (or ‘sample exit location’). In embodiments, the sample entrance location and the sample exit location may be separated by at most 20 cm, such as at most 10 cm. In particular, the (number of) collected photons may decrease exponentially with a higher separation. Hence, in embodiments, the sample entrance location and the sample exit location may be separated by at most 5 cm, especially by at most 4 cm, such as by at most 3 cm. The sample entrance location and the sample exit location may, in principle, be the same location (also see below). However, in embodiments, the sample entrance location and the sample exit location may also be spatially separated, such as by a distance of at least 0.1 cm, especially at least 0.2 cm, such as at least 0.5 cm, especially at least 1 cm.

[0050] The separation of the entrance location and the exit location may be measured across a surface of the sample or through the sample. The separation may be measured as a center-to-center distance, wherein the centers may be determined as a number-weighed average location for photons paths. In particular, the method may comprise employing a reflective or a transmissive setup. In a reflective setup, the entrance location and the exit location may (typically) be arranged at the same side of a sample, but may be separated by a distance measured over the surface of the sample. In a transmissive setup, the entrance location and the exit location may (typically) be arranged at opposite sides of a sample, and may be separated by a distance measured through the sample. Hence, the sample may have a first side and a second side, wherein the second side is configured opposite to the first side. As indicated above, the measurement path may pass through at least part of the sample. In embodiments, the first side may comprise the entrance location and the second side may comprise the exit location. This configuration may be referred to as “transmission geometry” or “transmission configuration” or similar terms. In alternative embodiments, the measurement path may pass through the first side twice, i.e., the first side may comprise the entrance location and the exit location. This configuration may be referred to as “reflection geometry” or “reflection configuration” or similar terms.

[0051] The measurement path downstream of the sample may especially differ from the measurement path upstream of the sample, i.e., in embodiments, the measurement radiation does not travel back along the same path (in the opposite direction). Hence, in embodiments, the exit location may differ from the entrance location and / or the measurement radiation may travel along different axes upstream and downstream from the sample.

[0052] The terms “upstream” and “downstream” relate to an arrangement of items or features relative to the propagation of the radiation from a radiation generating means (here especially the radiation source), wherein relative to a first position within a beam of radiation from the radiation generating means, a second position in the beam of radiation closer to the radiation generating means is “upstream”, and a third position within the beam of radiation further away from the radiation generating means is “downstream”.

[0053] In embodiments, the measurement path and the reference path may merge into a combined path downstream of the sample. The combined path may especially comprise combined radiation comprising both the measurement radiation from the measurement path and the measurement radiation from the reference path. Especially, the measurement radiation from the measurement path and the measurement radiation from the reference path may interfere with each other (in a frequency-dependent manner), providing a spectral interference pattern.

[0054] The method may further comprise detecting a spectral interference pattern of (or ‘in’) the (combined) measurement radiation travelling along the combined path using the photoelectric detector. Thereby, the method may comprise providing spectral signals (Sm,n) for each (combination) of the m measurement phases and the n pixels. In particular, each pixel of the photoelectric detector may (on average) provide RD*Tmmeasurements for each measurement phase. Each spectral signal Sm,n may thus comprise multiple (especially RD*Tm) spectral signal timepoints Sm,n,t corresponding to the different measurements (or “frames”).

[0055] The method may especially comprise detecting the spectral interference pattern in the frequency range used for the frequency sweep. For instance, in embodiments, the method may comprise detecting the spectral interference pattern in a frequency range of 5 - 2000 GHz, such as in the range of 10 - 1000 GHz, especially in the range of 10 - 100 GHz, such as in the range of 20 - 80 GHz. Hence, the photoelectric detector may especially be configured to detect radiation in the frequency range of 5 - 2000 GHz, such as in the range of 10 - 1000 GHz, especially in the range of 10 - 100 GHz, such as in the range of 20 - 80 GHz.

[0056] The method may further comprise determining the material property based on the spectral signals (Sm,n). It will be clear to the person skilled in the art that the generated data may be analyzed in various ways to arrive at various different (depth-dependent) material properties.

[0057] For instance, the method may involve determining a Depth / Time of Flight (TOF) resolved speckle contrast measurement of a turbid medium and / or a measurement of static and dynamic properties of a turbid medium.

[0058] In embodiments, the material property may comprise a flow velocity, such as a blood flow velocity, especially at a (target) material depth dm. In such embodiments, the method may comprise selecting a time-of-flight frequency range TOFR based on the material depth (dm). In particular, larger time-of-flight values may generally correspond to larger depths. By selecting a specific time-of-flight frequency range TOFR, the analysis may be directed to a specific depth range.

[0059] In further embodiments, the method may comprise selecting a plurality of time-of-flight frequency ranges TOFR. Selecting a plurality of different TOF frequency ranges TOFR may facilitate (consecutively or simultaneously) determining the flow velocity at different depth ranges. In embodiments, the plurality of time-of-flight frequency ranges TOFR may be non-overlapping (besides for endpoints). In alternative embodiments, the plurality of time-of-flight frequency ranges TOFR may be (partially) overlapping.

[0060] It will be clear to the person skilled in the art that the selection of the TOF frequency ranges TOFR can be performed at different timepoints during the analysis, i.e., it could be performed prior to performing measurements, after measuring but before subjecting the obtained signals to a Fourier transform (see below) or after the Fourier transform. In particular, the TOF frequency ranges TOFR may be selected prior to integrating power spectral densities Pm,n over the time-of-flight frequency range TOFR (see below).

[0061] The method may further comprise subjecting each spectral signal S m,n to a mean centering, i.e., a mean value may be subtracted from (all values in) each spectral signal Sm,n. In embodiments, the mean centering may be performed separately for each pixel, i.e., for each pixel the mean measurement value (for that pixel) is subtracted from the spectral signal Sm,nof that pixel. Generally, however, a (single) mean value for all measurements is subtracted from all spectral signals Sm,n. The mean centering prior to a Fourier transformation (see below) may facilitate removing the DC component, the removal of which may benefit the downstream analysis.

[0062] The method may further comprise subjecting each spectral signal Sm,n, optionally following mean centering, to a Fourier transformation to convert the signals into the frequency domain. The converted signals may subsequently be squared in order to provide power spectral densities Pm,n. Hence, in embodiments, the method may comprise subjecting the spectral signals Sm,n to a mean centering, subsequently to a Fourier transformation, and subsequently to squaring to provide power spectral densities Pm,n.

[0063] In further embodiments, the method may comprise subjecting the spectral signals Sm,n to a wavelet transformation, optionally after mean centering, and subsequently to squaring to provide the power spectral densities Pm,n.

[0064] The method may further comprise integrating the power spectral densities Pm,n over the (selected) time-of-flight frequency range TOFR to provide TOF-dependent energies Em,n. In particular, the method may provide a single TOF-dependent energy Em,n for the time- of-flight frequency range TOFR for each combination of the m measurement phases and the n pixels. In particular, in accordance with Parseval’s theorem, the TOF-dependent energies Em,n may be proportional to the photon numbers in the TOFR window. In embodiments wherein a plurality of time-of-flight frequency ranges TOFR are selected, the method may comprise providing a respective TOF-dependent energy Em,n for each time-of-flight frequency range TOFR.

[0065] In further embodiments, the method may comprise determining spatial speckle contrasts Kmbased on the TOF-dependent energies Em,n. In particular, the method may comprise determining the spatial speckle contrasts Kmover all pixels based on the TOF-dependent energies Em,nto obtain TOF-dependent speckle contrasts Km.

[0066] If the speckle contrasts at a given depth range (or TOFR) remain (relatively) constant over time, this may be indicative of a lack of movement at the depth range. In contrast, if the speckle contrast substantially varies over time, e.g., over successive measurement phases, this may be indicative of movement, such as flow, at the depth range. Hence, in embodiments, the method may further comprise detecting flow based on the spatial speckle contrasts Km.

[0067] Especially, in embodiments, the method may comprise determining the flow velocity based on the spatial speckle contrasts Km. In particular, the method may comprise (a) determining a spatial speckle correlation of the spatial speckle contrast Kmover the m (successive) measurement phases and (b) determining the flow velocity based on the spatial speckle correlation. In embodiments, the method may comprise determining a relative flow velocity (see below). In further embodiments, the method may comprise determining an absolute flow velocity (also see below)

[0068] Hence, in specific embodiments, the material property may comprise a flow velocity at a material depth dm, wherein the method comprises: (i) selecting a time-of-flight frequency range TOFR based on the material depth dm; (ii) subjecting each spectral signal Sm,n to a Fourier transformation, and subsequently to squaring to provide power spectral densities Pm,n; (iii) determining TOF-dependent energies Em,nin the power spectral densities Pm,nby integrating the power spectral densities Pm,nover the time-of-flight frequency range TOFR; (iv) determining spatial speckle contrasts Kmbased on the TOF-dependent energies Em,n; and (v) determining the flow velocity based on the spatial speckle contrasts Km. Optionally, in step (ii), the method may comprise subjecting each spectral signal Sm,n to a mean centering, subsequently to the Fourier transformation, and subsequently to the squaring to provide the power spectral densities Pm,n. In further embodiments, the material property may comprise flow velocities at a plurality of material depths dm, wherein the method comprises: (i) selecting time-of-flight frequency ranges TOFR based on the plurality of material depths dm; (ii) subjecting each spectral signal Sm,n to a Fourier transformation (optionally after mean centering), and subsequently to squaring to provide power spectral densities Pm,n; (iii) determining TOF-dependent energies Em,n, TOF in the power spectral densities Pm,n for each time-of-flight frequency range TOFR by integrating the power spectral densities Pm,n over each of the respective time-of-flight frequency ranges TOFR; (iv) determining spatial speckle contrasts Km, TOF for each of the time-of-flight frequency ranges TOFR based on the TOF-dependent energies Em,n, TOF; and (v) determining the flow velocities based on the spatial speckle contrasts Km, TOF.

[0069] In embodiments, the material property may (further) comprise one or more of a reduced scattering coefficient ps’ and an absorption coefficient pa. In embodiments, the method may comprise determining the reduced scattering coefficient (ps’) and the absorption coefficient (pa) based on the spectral signals Sm,n, especially based on speckle contrasts Km.

[0070] The availability of the reduced scattering coefficient ps’ and the absorption coefficient pamay facilitate determining the flow velocity with increased accuracy. Hence, in embodiments, the method may comprise determining the flow velocity based on the speckle contrasts Km, the reduced scattering coefficient (ps’) and the absorption coefficient (pa).

[0071] Hence, in specific embodiments, the material property may (further) comprise a reduced scattering coefficient (ps’), and an absorption coefficient (pa). Especially, the method may comprise determining the reduced scattering coefficient (ps’) and the absorption coefficient (pa).

[0072] In particular, in embodiments, the material property further comprises a reduced scattering coefficient ps’ and an absorption coefficient pa. In such embodiments, the method may comprise performing a second measurement. The second measurement may comprise providing second measurement radiation along the measurement path and along the reference path. Similar to the (first) measurement radiation described above, the second measurement radiation may be coherent and may comprise a plurality of (second) measurement phases, especially m2 (second) measurement phases, wherein m2 > 2. The number of (second) measurement phases may be selected independently from the number of (first) measurement phases (see above), i.e., m and m2 may be selected independently of one another. In specific embodiments, m=m2. In contrast to the (first) measurement radiation, second measurement durations Tm2 of the second measurement phases may be varied between a minimum measurement duration Tmin and a maximum measurement duration Tmax, especially in a stepwise manner, such as with equal sized steps. In particular, for each second measurement duration Tm2 may apply that Ro*Tm2 > 100. Further, the second measurement may comprise a second frequency sweep over a frequency range selected from the range of 10 - 1000 GHz. The second measurement may further comprise detecting a second spectral interference pattern of the second measurement radiation travelling along the combined path using the photoelectric detector to provide a second spectral signal Sm2,n for each of the m2 measurement phases and the n pixels. The second measurement may comprise selecting a time-of-flight frequency range TOFR based on the material depth dm, especially one or more time-of-flight frequency ranges TOFR based on one or more material depths dm. Further, the second measurement may comprise subjecting the second spectral signals Sm2,n to Fourier transformation, and subsequently to squaring to provide second power spectral densities Pm2,n. Optionally, the second measurement may comprise subjecting the second spectral signals Sm2,n to mean centering prior to the Fourier transformation. The second measurement may further comprise determining second TOF-dependent energies Em2,nin the second power spectral densities Pm2,n by integrating the second power spectral densities Pm2,n over the time-of-flight frequency range TOFR, and especially determining second spatial speckle contrasts Km2 based on the second TOF-dependent energies Em2,n. In general, the same time-of-flight frequency range(s) TOFR used for flow velocity determinations (see above) may also be used in the second measurement. The second measurement may further comprise determining TOF-dependent speckle correlation times TCbased on the second spatial speckle contrasts Km2. Further, the second measurement may comprise determining the reduced scattering coefficient ps’, and the absorption coefficient pabased on the TOF-dependent speckle correlation times TCand one or more of the power spectral densities Pm,n and the second power spectral densities Pm2,n, especially based on the power spectral densities Pm,n, or especially based on the second power spectral densities Pm2,n.

[0073] Hence, in specific embodiments, the material property may further comprise a reduced scattering coefficient ps’, and an absorption coefficient pa, wherein the method comprises performing a second measurement comprising: (i) providing second measurement radiation along the measurement path and along the reference path, wherein the second measurement radiation is coherent, wherein the second measurement radiation comprises m2 second measurement phases, wherein m2 > 2, wherein second measurement durations Tm2 of the second measurement phases are varied between a minimum measurement duration Tmin and a maximum measurement duration Tmax, wherein for each second measurement phase applies that Ro*Tm2 > 100, wherein each second measurement phase comprises a second frequency sweep over a frequency range selected from the range of 10 - 1000 GHz; and (ii) detecting a second spectral interference pattern of the second measurement radiation travelling along the combined path using the photoelectric detector to provide a second spectral signal Sm2,n for each of the m2 measurement phases and the n pixels. Especially, in embodiments, the second measurement may further comprise: (iii) subjecting the second spectral signals Sm2,n to Fourier transformation, and subsequently to squaring to provide second power spectral densities Pm2,n; (iv) determining second TOF-dependent energies Em2,nin the second power spectral densities Pm2,n by integrating the second power spectral densities Pm2,n over the time-of-flight frequency range TOFR; (V) determining second spatial speckle contrasts Km2 based on the second TOF-dependent energies Em2,n; (vi) determining TOF-dependent speckle correlation times TCbased on the second spatial speckle contrasts Km2; and (vii) determining the reduced scattering coefficient ps’, and the absorption coefficient pabased on the TOF-dependent speckle correlation times TCand one or more of the power spectral densities Pm,n and the second power spectral densities Pm2,n.

[0074] In embodiment, the method may comprise the (first) measurement as described above (also see first procedure described below). Additionally or alternatively, in embodiments, the method may comprise the second measurement as described above (also see second procedure described below. In particular, in the (first) measurement, the measurement duration Tmof the m measurement phases may be kept constant. In contrast, in the second measurement, the second measurement durations Tm2 of the m2 second measurement phases may be varied between a minimum measurement duration Tmin and a maximum measurement duration Tmax.

[0075] In embodiments, the method may especially be a non-medical method.

[0076] In a second aspect, the invention may provide a system. The system may comprise one or more of a radiation source, a photoelectric detector, a hosting space, and a control system. In embodiments, the radiation source may comprise a swept laser source. In further embodiments, the photoelectric detector may have a frame rate RD, especially wherein the frame rate RD > 10 kHz. Further, the photoelectric detector may comprise an array comprising n pixels, especially wherein n > 100. The radiation source may especially be configured to provide measurement radiation to the photoelectric detector via a measurement path and via a reference path, especially wherein the measurement radiation is coherent. The measurement path may pass through (at least part of) the hosting space, especially wherein the measurement path upstream of the hosting space differs from the measurement path downstream of the hosting space. Further, the measurement path and the reference path may merge into a combined path downstream of the hosting space and upstream of the photoelectric detector, especially thereby providing combined radiation comprising a spectral interference pattern. In embodiments, the control system may be configured to execute an operational mode. In the operational mode, the hosting space may be configured to host a sample. Further, in the operational mode, the radiation source may be configured to provide the measurement radiation (along the measurement path and along the reference path). In embodiments, the measurement radiation may comprise m measurement phases, especially wherein m > 2. Especially, the measurement phases may have a (same) measurement duration Tm, especially wherein Ro*Tm > 100. In embodiments, each measurement phase may comprise a (same) frequency sweep over a frequency range selected from the range of 10 - 1000 GHz, such as from the range of 10 -100 GHz. In the operational mode, the photoelectric detector may be configured to detect a spectral interference pattern of the (combined) measurement radiation travelling along the combined path to provide spectral signals (Sm,n) for each (combination) of the m measurement phases and n pixels, and especially to provide the spectral signals (Sm,n) to the control system.

[0077] In specific embodiments, the system comprises a radiation source, a photoelectric detector, a hosting space, and a control system, wherein the radiation source comprises a swept laser source, wherein the photoelectric detector has a frame rate RD and comprises a 2D array comprising n pixels, wherein the frame rate RD > 10 kHz, and wherein n > 100, wherein the radiation source is configured to provide measurement radiation to the photoelectric detector via a measurement path and via a reference path, wherein the measurement radiation is coherent, wherein the measurement path passes through the hosting space, wherein the measurement path upstream of the hosting space differs from the measurement path downstream of the hosting space, and wherein the measurement path and the reference path merge into a combined path downstream of the hosting space and upstream of the photoelectric detector, wherein the control system is configured to execute an operational mode, wherein in the operational mode: the hosting space is configured to host a sample; the radiation source is configured to provide the measurement radiation, wherein the measurement radiation comprises m measurement phases, wherein m > 2, wherein the measurement phases have a measurement duration Tm, wherein Ro*Tm > 100, wherein each measurement phase comprises a frequency sweep over a frequency range selected from the range of 10 - 1000 GHz; and the photoelectric detector is configured to detect a spectral interference pattern of the measurement radiation travelling along the combined path to provide spectral signals Sm,n for each of the m measurement phases and n pixels, and to provide the spectral signals Sm,n to the control system.

[0078] The system may facilitate performing the method of the invention (see above). In particular, the system may facilitate providing the spectral signals Sm,n from which a material property, such as a (blood) flow rate can be determined.

[0079] The system may comprise one or more of a hosting space, a radiation source, a photoelectric detector, and a control system. In particular, in embodiments, the system may comprise (each of) the radiation source, the photoelectric detector, the hosting space, and the control system.

[0080] In embodiments, the system may comprise the hosting space. The hosting space may be configured to host a sample, such as a sample selected from the group a wall, a floor, a ceiling, a road, a pipe, a tube, (a part of) an animal, such (a part of) a human, like a limb, especially a head of an animal, more especially a brain of an animal. Especially, the hosting space may be configured to host the sample of the method as defined above. The hosting space may, for instance, comprise a hosting space element configured to engage the sample, such as to keep the sample in a predefined place and / or configuration. The hosting space may especially be configured to host the sample in a hosting site. The term “hosting site” may herein thus refer to a site (or “volume”) wherein a sample would be hosted during operation of the system.

[0081] In embodiments, the system may comprise a radiation source configured to provide measurement radiation. The radiation source may especially comprise a swept laser source, i.e., a radiation source configured to provide a frequency sweep of laser radiation. In embodiments, the radiation source may be configured to provide coherent measurement radiation.

[0082] The radiation source may especially be configured to provide the measurement radiation to the photoelectric detector via a measurement path and via a reference path. The measurement path and the reference path may partially overlap, especially directly downstream from the radiation source and directly upstream from the photoelectric detector, but may diverge in between.

[0083] The measurement path may especially pass through (at least part of) the hosting space, especially through (at least part of) the hosting site. In particular, the radiation source (and optionally any optics) may be configured such that if the hosting space hosts a sample (in the hosting site), the measurement path passes through (at least part of) the sample. Further, the measurement path upstream of the hosting space may differ from the measurement path downstream of the hosting space, i.e., in embodiments, the measurement radiation does not travel back along the same path (in the opposite direction). Especially, the measurement path downstream of the sample may be spatially separated from the measurement path upstream of the sample or, if intersecting, be arranged along a different axis.

[0084] In particular, the measurement path may enter the hosting site, especially the sample, at a hosting site entrance location (or ‘sample entrance location’), pass through at least part of the hosting site, and exit the hosting site, especially the sample, at a hosting site exit location (or ‘sample exit location’). In embodiments, the hosting site entrance location and the hosting site exit location may be separated by at most 20 cm, such as at most 10 cm, especially at most 5 cm. In further embodiments, the hosting site entrance location and the hosting site exit location may be separated by at most 4 cm, such as by at most 3 cm. The hosting site entrance location and the hosting site exit location may, in principle, be the same location (also see above). However, in embodiments, the hosting site entrance location and the hosting site exit location may also be spatially separated, such as by a distance of at least 0.1 cm, especially at least 0.2 cm, such as at least 0.5 cm, especially at least 1 cm.

[0085] In embodiments, the reference path may be (essentially) arranged outside (or “at a distance”) of the hosting space, especially outside of the hosting site, i.e., the reference path may (essentially) not pass through the hosting space, such as through the hosting site. In particular, during operation of the system, the reference path may be (essentially) arranged outside of the sample.

[0086] The system may further comprise the photoelectric detector. The photoelectric detector may be configured for detecting the measurement radiation and for providing a related signal.

[0087] The photoelectric detector may have a frame rate RD, i.e., the photoelectric detector may be configured to take RD frames per second. In embodiments, RD may be selected from the range of > 1 kHz, such as > 5 kHz, especially > 10 kHz. In further embodiments, RD may be selected from the range of > 20 kHz, such as from the range of > 50 kHz, such as from the range of > 100 kHz, especially from the range of > 200 kHz. In particular, a high frame rate may be beneficial for the SNR. In further embodiments, RD may be selected from the range of < 4 MHz, such as from the range of < 2 MHz, such as from the range of < 1 MHz, especially from the range of < 500 kHz. For instance, in embodiments, the frame rate RD may be selected from the range of 50 kHz - 4 MHz, such as from the range of 100 kHz - 2 MHz, especially from the range of 100 kHz - 1 MHz.

[0088] The photoelectric detector may further comprise an array, especially a ID array, or especially a 2D array, comprising n pixels. In embodiments, n > 10, such as > 50, especially > 100. In further embodiments, n > 500, such as > 1000, especially > 2000. In further embodiments n > 5000, such as > 10000. In further embodiments, n < 10000000, such as < 5000000, especially < 2000000. In further embodiments, n < 1000000, such as < 100000, especially < 50000. In embodiments, the array may comprise an ni*njarray, wherein ni*nj= ntot(see above), especially wherein ni*nj=n. In further embodiments, ni> 2 and nj> 2, i.e. the array may comprise a 2D array. In specific embodiments, ni=nj.

[0089] As described above, the photoelectric detector may especially comprise a CMOS camera. In further embodiments, the photoelectric detector may comprise a CCD camera.

[0090] In further embodiments, the system comprises the control system. The control system may be configured to control the system, especially one or more of the radiation source, the photoelectric detector, and the hosting space. Further, in embodiments wherein the system comprises optics (see below), the control system may be configured to control the optics, such as control the movement of moveable optics.

[0091] The term “controlling” and similar terms herein may especially refer at least to determining the behavior or supervising the running of an element. Hence, herein “controlling” and similar terms may e.g. refer to imposing behavior to the element (determining the behavior or supervising the running of an element), etc., such as e.g. measuring, displaying, actuating, opening, shifting, changing temperature, etc.. Beyond that, the term “controlling” and similar terms may additionally include monitoring. Hence, the term “controlling” and similar terms may include imposing behavior on an element and also imposing behavior on an element and monitoring the element. The controlling of the element can be done with a control system. The control system and the element may thus at least temporarily, or permanently, functionally be coupled. The element may comprise the control system. In embodiments, the control system and the element may not be physically coupled. Control can be done via wired and / or wireless control. The term “control system” may also refer to a plurality of different control systems, which especially are functionally coupled, and of which e.g. one master control system may be a control system and one or more others may be slave control systems.

[0092] The system, especially the control system, may have an operational mode. The term “operational mode” may also be indicated as “controlling mode”. The system, or apparatus, or device (see further also below) may execute an action in a “mode” or “operational mode” or “mode of operation”. Likewise, in a method an action, stage, or step may be executed in a “mode” or “operation mode” or “mode of operation”. This does not exclude that the system, or apparatus, or device may also be adapted for providing another operational mode, or a plurality of other operational modes. Likewise, this does not exclude that before executing the mode and / or after executing the mode one or more other modes may be executed. However, in embodiments, a control system may be available, that is adapted to provide at least the operational mode. Would other modes be available, the choice of such modes may especially be executed via a user interface, though other options, like executing a mode in dependence of a sensor signal or a (time) scheme, may also be possible. The operational mode may in embodiments also refer to a system, or apparatus, or device, that can only operate in a single operational mode (i.e. “on”, without further tunability).

[0093] In embodiments, the control system may thus be configured to execute the operational mode. Especially, the control system may be configured to execute (at least part of) the method of the invention (as defined above).

[0094] In the operational mode, the hosting space may (be configured to) host a sample, especially at the hosting site. The hosting space may comprise a supporting structure for hosting the sample. The hosting space may further comprise engagement elements configured to engage the sample, such as to keep the sample in place. In particular, during the operational mode, the hosting space may host the sample.

[0095] Further, in the operational mode, the radiation source may (be configured to) provide the measurement radiation. As described above, the radiation source may provide the measurement radiation along a measurement path and along a reference path, wherein the measurement path passes through the hosting space, such as through the hosting site, especially through the sample hosted in the hosting space, and especially wherein the reference path is arranged outside of the hosting space. In particular, the radiation source may be configured to provide the measurement radiation with (or “in”) m measurement phases, wherein m > 2, such as > 3, especially > 5, such as > 10. The radiation source may especially be configured to provide a frequency sweep of measurement radiation in each measurement phase. The frequency sweeps in successive measurement phases may be (essentially) identical. In embodiments, in the operational mode, the radiation source may (be configured to) provide a (same) frequency sweep in each measurement phase, especially over a frequency range selected from the range of 5 - 2000 GHz, such as from the range of 10 - 1000 GHz, especially from the range of 10 - 100 GHz, such as from the range of 20 - 80 GHz.

[0096] In embodiments, the frequency sweep may comprise a (linear) change from a first frequency fi to a second frequency fi, wherein the first frequency fi and the second frequency fi are both selected from the frequency range. Similarly, a frequency sweep may comprise a (linear) change from a first frequency fi to a second frequency fi and back. In embodiments, the frequency sweeps may especially have (essentially) the same pattern, i.e., the same first frequency fi, second frequency fi, and rate of change. In further embodiments, each frequency sweep may comprise a monotonic increase of the frequency. In further embodiments, each frequency sweep may comprise a monotonic decrease of the frequency. Hence, in embodiments, the frequency sweep comprises a linear frequency sweep. In further embodiments, each frequency sweep may comprise both increases and decreases in frequency. For instance, the frequency sweeps may be shaped according to a (sine) waveform or may have a A-shape. Hence, in embodiments, the frequency sweep may comprise a nonlinear frequency sweep, such as a sine frequency sweep.

[0097] In further embodiments, the frequency sweep may comprise (monotonically) sweeping from a first frequency fi to a second frequency fi and optionally back from the second frequency fi to the first frequency fi. Especially, in such embodiments, fi and fi may differ by at least 5 GHz, such as by at least 10 GHz, especially by at least 20 GHz. In further embodiments, fi and fi may differ by at most 1000 GHz, such as by at most 100 GHz, especially by at most 50 GHz.

[0098] In further embodiments, each measurement phase may have a (same) measurement duration Tm. In particular, the frequency sweep in each measurement duration may have a (same) measurement duration Tm. The measurement duration Tmmay especially be selected to facilitate generating a substantial number of frames by the photoelectric detector during each measurement phase. In particular, in embodiments, the measurement duration Tmmay be selected such that RD*Tm≥ 10, such as ≥ 50, especially ≥ 100. In further embodiments, the measurement duration Tmmay be selected such that RD*Tm≥ 1000, such as > 2000, especially > 5000. In further embodiments, the measurement duration Tmmay be selected such that RD*Tm≤ 10000, such as ≤ 5000, especially ≤ 2000, such as ≤ 1000.

[0099] For example, when RD*Tm= 100, the photoelectric detector may generate 100 images for each measurement phase (and for each pixel; see below). Although short measurement phases (small Tm) may be considered beneficial in view of picking up on fast sample dynamics, a large value of RD*Tm, which may be obtainable by selecting a long measurement duration Tm, may be beneficial in view of the SNR. In embodiments, the measurement duration Tmmay especially be selected such that Ro*Tm is selected from the range of 50 - 2000, such as from the range of 100 - 1000, especially from the range of 200 - 500.

[0100] In particular, in embodiments, the control system may be configured to select Tmin view of RD, such as to select Tmto satisfy Ro*Tm> 10, such as > 50, especially > 100. In further embodiments, Tm> 0.0001 s, such as > 0.001 s. In further embodiments, Tm> 0.01 s, such as > 0.1 s. In further embodiments, Tmis selected from the range of < 2 s, such as < 1 s, especially < 0.1 s. For instance, in embodiments, Tmmay be selected from the range of 0.001 - 1 s, especially from the range of 0.01 - I s.

[0101] As described above, the measurement path and the reference path may merge into a combined path downstream of the sample (for the measurement path).

[0102] During the operational mode, the photoelectric detector may (be configured to) detect a spectral interference pattern of the (combined) measurement radiation travelling along the combined path to provide spectral signals Sm,n for each (combination) of the m measurement phases and the n pixels. The photoelectric detector may further be configured to provide the spectral signals Sm,n to the control system.

[0103] The spectral signals may be informative on material properties of the sample, such as on flow rates of (or within) the sample. In particular, the material properties may be derived from the spectral signals Sm,n.

[0104] In embodiments, the control system may be configured to determine a material property of the sample based on the spectral signals Sm,n. Especially, during the operational mode, the control system may (be configured to) determine the material property based on the spectral signals Sm,n In embodiments, the material property may comprise a dynamic material property. In embodiments, the material property may comprise one or more of a material composition, a flow velocity, a flow velocity profile, a reduced scattering coefficient of the sample, a rheological parameter, such as viscosity and / or elasticity, a temperature, an (average) absorption coefficient, and a size of a particle undergoing Brownian motion. Especially, the material property may comprise a flow velocity, such as a blood flow velocity. In further embodiments, the material property may comprise a diffusion coefficient, especially a Brownian diffusion coefficient.

[0105] For instance, in embodiments, the material property may comprise a flow velocity at a material depth dm. In such embodiments, in the operational mode, the control system may (be configured to) (i) select a time-of-flight frequency range TOFR based on the material depth (dm); (ii) subject each spectral signal Sm,n to a Fourier transformation, optionally following mean centering (see above), and subsequently to squaring to provide power spectral densities Pm,n; (iii) determine TOF-dependent energies Em,nin the power spectral densities Pm,nby integrating the power spectral densities Pm,nover the time-of-flight frequency range TOFR; (iv) determine spatial speckle contrasts Kmbased on the TOF-dependent energies Em,n; (v) determine the flow velocity based on the spatial speckle contrasts Km. For instance, the control system may (be configured to) determine a correlation of the spatial speckle contrasts Kmover the (successive) measurement phases, and determine the flow velocity based on the correlation. Optionally, in step (ii) the control system may be configured to subject each spectral signal Sm,n to a mean centering, subsequently to the Fourier transformation, and subsequently to the squaring to provide the power spectral densities Pm,n.

[0106] In further embodiments, the material property may comprise flow velocities at a plurality of material depths dm. In such embodiments, in the operational mode, the control system may (be configured to): (i) select time-of-flight frequency ranges TOFR based on the material depths dm; (ii) subject each spectral signal Sm,nto a Fourier transformation, optionally following a mean centering, and subsequently to squaring to provide power spectral densities Pm,n; (iii) determine TOF-dependent energies Em,n, TOFin the power spectral densities Pm,n for each time-of-flight frequency range TOFR by integrating the power spectral densities P m,n over each of the (respective) time-of-flight frequency ranges TOFR; (iv) determine spatial speckle contrasts Km, TOF for each of the time-of-flight frequency ranges TOFR based on the TOF-dependent energies Em,n, TOF; and (v) determine the flow velocities based on the spatial speckle contrasts Km, TOF. For instance, the control system may (be configured to) determine correlations of the spatial speckle contrasts Km, TOF over the (successive) measurement phases, and determine the flow velocities based on the correlations.

[0107] In embodiments, the material property may (further) comprise one or more of a reduced scattering coefficient ps’ and an absorption coefficient pa. In embodiments, in the operational mode, the control system may (be configured to) determine the reduced scattering coefficient (ps’) and the absorption coefficient (pa) based on the spectral signals Sm,n, especially based on the speckle contrasts Km.

[0108] In embodiments, the system may be configured to operate in a transmission geometry, i.e., the measurement path may enter the sample at a first side and exit the sample at a second side, wherein the second side is opposite of the first side.

[0109] In further embodiments, the system may be configured to operate in a reflection geometry, i.e., the measurement path may enter and exit the sample at a (same) first side.

[0110] The system may, in embodiments, further comprise one or more optical components to reduce ambient noise, to guide the measurement radiation, and / or to control the measurement radiation.

[0111] For instance, in embodiments, the system may comprise a multimode fiber (or “multimode optical fiber”), especially a plurality of multimode fibers. The multimode fiber may be arranged to provide at least part of the measurement path between the hosting space and the photoelectric detector. In particular, the multimode fiber may be arranged to receive (or “capture”) the measurement radiation leaving the hosting space, especially the measurement radiation leaving the hosting site at the hosting site exit location, or especially the measurement radiation leaving the sample at the (sample) exit location. The use of multimode fibers to capture the measurement radiation downstream from the sample and to provide the measurement radiation may reduce ambient noise, and may therefore increase the SNR. In further embodiments, the radiation source may be configured to provide the measurement radiation to a hosting space entry location and the multimode fibers are configured to receive the measurement radiation from a hosting space exit location. Especially, a distance du (along or through the sample) between the hosting space entry location and the hosting space exit location may be selected from the range of 0 - 5 cm, especially from the range of 0.5 - 5 cm.

[0112] In further embodiments, the system may comprise one more optical components selected from the group comprising a lens, such as a cylindrical lens, a polarization rotator, a polarizer, and a beam splitter. The one or more optical components may be configured to facilitate the measurement radiation to travel along the measurement path and the reference path and to merge into a combined path upstream of the photoelectric detector.

[0113] For instance, in embodiments, the system may comprise a lens configured (directly) upstream of the photoelectric detector. The lens, especially a cylindrical lens, may be configured to receive the (combined) measurement radiation and to provide the measurement radiation to the photoelectric detector. In particular, the lens may project the speckle in the imaging area of the photoelectric detector, such as in a (cropped) rectangular area for obtaining a high frame rate. The photoelectric detector may thus be configured in a radiation-receiving relationship with the lens.

[0114] In further embodiments, the system may comprise a first beam splitter. The first beam splitter may be arranged in a radiation-receiving relationship with the radiation source. The first beam splitter may especially be configured to split the measurement radiation (received by the first beam splitter) into measurement radiation traveling along the measurement path and measurement radiation traveling along the reference path. In embodiments, the first beam splitter may be configured to direct 50 - 99 % of the radiation towards the measurement path, such as 70 - 99%, especially 80 - 95%.

[0115] In further embodiments, the system may comprise a second beam splitter (or “beam combiner”). The second beam splitter may be configured to receive the measurement radiation traveling along the measurement path and the reference radiation traveling along the reference path and to provide (combined) measurement radiation traveling along the combined path. Hence, the second beam splitter may be configured to merge the measurement path and the reference path into the combined path.

[0116] In further embodiments, the system may further comprise a polarization rotator and a polarizer, wherein the polarization rotator is arranged in the reference path, especially upstream from the second beam splitter. The polarizer may be arranged in the combined path and upstream of the photoelectric detector, and especially downstream of the second beam splitter. In embodiments, the control system may be configured to control a polarization state of the measurement radiation traveling along the reference path by controlling the polarization rotator. Thereby, the control system, especially the polarization rotator, may control the amount of measurement radiation from the reference path that arrives at the photoelectric detector. In particular, the control system may thereby control the ratio of measurement radiation from the measurement path and measurement radiation from the reference path that ends up in the combined path. Especially, the control system may be configured to approximately match the amount of radiation from the different paths. Additionally or alternatively, the control system may be configured to control how much measurement radiation from the reference path arrives at the photoelectric detector in order to avoid saturating the photoelectric detector.

[0117] In further embodiments, the system may comprise a (third) beam splitter and a photodetector, wherein the beam splitter is arranged within the reference path, and wherein the beam splitter is configured to split off part of the measurement radiation to the photodetector (via a monitoring path), especially via a single-mode fiber. The photodetector may be configured to monitor one or more optical properties of the measurement radiation and to provide a related monitoring signal to the control system, especially wherein the control system is configured to control the radiation source based on the related monitoring signal. Such embodiments may facilitate monitoring the measurement radiation for (unexpected) fluctuations and accounting for such fluctuations, which may thereby improve the reliability of the measurements.

[0118] The term “related monitoring signal” may herein refer to a signal that is related to the detected optical properties. In particular, the related monitoring signal may comprise raw and / or processed data related to the (detected) optical properties.

[0119] In embodiments, the system may be configured to execute the method of the invention.

[0120] In a further aspect, the invention may provide a (non-transitory) computer program product comprising program instructions for execution on a control system functionally coupled to or comprised by a system comprising a (swept laser) radiation source and a photoelectric detector. In embodiments, the program instructions, when executed by the control system, may cause the control system to carry out the method of the invention. Additionally or alternatively, the program instructions, when executed by the control system, may cause the control system to carry out the operational mode as defined herein.

[0121] In a further aspect, the invention may provide a data carrier, carrying thereupon (non-transitory) program instructions which, when executed by a control system functionally coupled to or comprised by a system comprising a (swept laser) radiation source and a photoelectric detector, cause the control system to (a) carry out the method of the invention, and / or (b) the operational mode as defined herein.

[0122] The embodiments described herein are not limited to a single aspect of the invention. For example, an embodiment describing the method may, for example, further relate to the system, especially to an operational mode of the system, or especially to the control system. Similarly, an embodiment of the system describing an operation of the system may further relate to embodiments of the method. In particular, an embodiment of the method describing an operation (of the system) may indicate that the system may, in embodiments, be configured for and / or be suitable for the operation. Similarly, an embodiment of the system describing actions of (a stage in) an operational mode may indicate that the method may, in embodiments, comprise those actions.

[0123] BRIEF DESCRIPTION OF THE DRAWINGS

[0124] Embodiments of the invention will now be described, by way of example only, with reference to the accompanying schematic drawings in which corresponding reference symbols indicate corresponding parts, and in which: Fig. 1A-B schematically depict embodiments of the method and the system of the invention. Fig. 2A-F schematically depict further embodiments of the method and system of the invention. Fig. 3 schematically depicts embodiments of the method of the invention and of the operational mode of the system. Fig.

[0125] 4A-B schematically depicts further aspects of the method and the operational mode of the system. Fig. 5 A-C schematically depicts further aspects of the method and the operational mode of the system. The schematic drawings are not necessarily on scale.

[0126] DETAILED DESCRIPTION OF THE EMBODIMENTS

[0127] Fig. 1A-B schematically depict embodiments of the method for determining a material property of a sample 50 using a photoelectric detector 120. The photoelectric detector 120 may have a frame rate RD and may comprise an array 122 comprising n pixels 125. In embodiments, the frame rate RD > 10 kHz and n > 100. In the depicted embodiment, the method comprises providing measurement radiation 111, especially coherent measurement radiation 111, along a measurement path 10 and along a reference path 20. In particular, the measurement radiation 111 may be provided using a radiation source 110, such as a swept laser source 115, and may be split over the measurement path 10 and the reference path 20 using a beam splitter 140, especially a first beam splitter 141. The measurement radiation 111 comprises m measurement phases 40 (also see Fig. 3), wherein m > 2, wherein the measurement phases 40 have a (same) measurement duration (Tm), and wherein Ro*Tm > 100. In particular, each measurement phase 40 may comprise a (same) frequency sweep 45 over a frequency range selected from the range of 10 - 1000 GHz. As schematically depicted, the measurement path 10 enters the sample 50 at a (sample) entrance location 51, passes through at least part of the sample 50, and exits the sample 50 at a (sample) exit location 52. Especially, a distance du (along or through the sample 50) between the entrance location 51 and the exit location 52 is selected from the range of 0 - 5 cm. In the depicted embodiment, du is nonzero, i.e., the entrance location 51 and the exit location 52 are different locations (also see Fig. 2A-F). Downstream of sample 50 the measurement path 10 and the reference path 20 merge into a combined path 30, especially via a second beam splitter 140, 142. In the depicted embodiment, the measurement path 10 passes through a multimode fiber 130, especially between the sample 50 and the second beam splitter 140, 142. Hence, the method may comprise receiving (or “capturing”) the measurement radiation 111 from the exit location 52 of the sample 50 using a multimode fiber 130, wherein (at least part of) the measurement path 10 passes through the multimode fiber 130. In the depicted embodiment, the method further comprises detecting a spectral interference pattern of the (combined) measurement radiation 111 travelling along the combined path 30 using the photoelectric detector 120, especially to provide spectral signals Sm,nfor each (combination) of the m measurement phases 40 and the n pixels 125. The method may further comprise determining the material property based on the spectral signals Sm,n(also see Fig. 3).

[0128] As schematically depicted in Fig. 1 A, the measurement radiation 111 may travel along different paths within the sample 50. In particular, the measurement depth dmreached by the measurement radiation 111 may be frequency-dependent. In the depicted example, measurement radiation 111 having a first measurement frequency reaches a first measurement depth dmi, measurement radiation 111 having a second measurement frequency reaches a second measurement depth dm2. and measurement radiation 111 having a third measurement frequency reaches a third measurement depth dm3. As each measurement phase comprises a frequency sweep, each of the three measurement depths dmmay be reached in each measurement phase.

[0129] Fig. 1A further schematically depicts an embodiment of the system 100 of the invention. In the depicted embodiment, the system comprises a radiation source 110, a photoelectric detector 120, a hosting space 150, and a control system 300. Specifically, the radiation source 110 comprises a swept laser source 115 and the photoelectric detector 120 has a frame rate RD and comprises an array 122 comprising n pixels 125, wherein the frame rate RD > 10 kHz, and wherein n > 100. As schematically depicted, the radiation source 110 is configured to provide (coherent) measurement radiation 111 to the photoelectric detector 120 via a measurement path 10 and via a reference path 20. In particular, the radiation source may provide the measurement radiation to a first beam splitter 140,141 configured to split the measurement radiation over the measurement path 10 and the reference path 20. The measurement path 10 passes through (at least part of) the hosting space 150, wherein the measurement path 10 upstream of the hosting space 150 differs from the measurement path downstream of the hosting space 150. In contrast, the reference path 20 is arranged outside of the hosting space 150. The measurement path 10 and the reference path 20 merge into a combined path 30 downstream of the hosting space 150 and upstream of the photoelectric detector 120, especially via a second beam splitter 140,142. In particular, the control system 300 is configured to execute an operational mode. In the operational mode, the hosting space 150 is configured to host a sample 50, as depicted in Fig. 1A. Further, in the operational mode, the radiation source 110 is configured to provide the measurement radiation 111 with m measurement phases 40 (also see Fig. 3), wherein m > 2, and wherein the measurement phases 40 have a (same) measurement duration Tm, especially wherein Ro*Tm > 100. In particular, each measurement phase 40 may comprise a (same) frequency sweep 45 over a frequency range selected from the range of 10 - 1000 GHz (also see Fig. 3). Further, in the operational mode, the photoelectric detector 120 is configured to detect a spectral interference pattern of the (combined) measurement radiation 111 travelling along the combined path 30 to provide spectral signals Sm,n for each (combination) of the m measurement phases 40 and the n pixels 125, and to provide the spectral signals Sm,nto the control system 300.

[0130] In further embodiments, in the operational mode, the control system 300 may (be configured to) determine a material property of the sample 50 based on the spectral signals Sm,n. In the depicted embodiment, the system 100 further comprises a multimode fiber 130. The multimode fiber 130 provides at least part of the measurement path 10 between the hosting space 150 and the photoelectric detector 120. In particular, the multimode fiber is configured to receive the measurement radiation 111 from the exit location 52, and especially to guide the measurement radiation 111 towards the second beam splitter 140,142.

[0131] Further, in the depicted embodiment, the system 100 comprises a lens 190, especially a Powell lens 193, arranged between the first beam splitter 140,141 and the second beam splitter 140,142. The Powell lens 193 may especially facilitate ‘stretching’ the measurement radiation 111 to fill all pixels 125 of the photoelectric detector 120.

[0132] In particular, in Fig. 1A-B, the laser beam is split into a reference and measurement arm. In the reference arm, the laser beam is stretched into a line by a Powell lens to fill all pixels of the camera. In the measurement arm, the laser beam illuminates the sample and remitted photons are collected and interfere with the reference beam in the Beam Splitter and then they are projected onto the camera, especially using a cylindrical lens pair (see Fig.

[0133] 2). In particular, the system 100 may comprise a pair of cylindrical lenses configured perpendicularly to one another.

[0134] Fig. 1B schematically depicts a further embodiment of the system 100. In the depicted embodiment, the system 100 further comprises a (rotatable or moveable) polarization rotator 160 and a polarizer 170. The polarization rotator 160 is arranged in the reference path (and upstream from a second beam splitter 142). The position of the polarization rotator may affect a polarization state of the measurement radiation 111 downstream of the polarization rotator 160, such as (indirectly) received by the polarizer 170 and, by extent, the amount of measurement radiation 111 from the reference path 20 received by the photoelectric detector 120. In particular, in the depicted embodiment, the control system 300 may (be configured to) control a polarization state of the measurement radiation 111 traveling along the reference path 20 by controlling the polarization rotator 160.

[0135] Further, in the depicted embodiment, the system 100 comprises a third beam splitter 140,143 and a photodetector 180, wherein the third beam splitter 140,143 is arranged within the reference path 20, and wherein the third beam splitter 140,143 is configured to split off part of the measurement radiation 111 to the photodetector 180. In particular, part of the measurement radiation 111 is split off via a monitoring path 80, especially via a single-mode fiber 135, towards the photodetector. The photodetector 180 may be configured to monitor one or more optical properties of the measurement radiation 111 and to provide a related monitoring signal to the control system 300. For instance, the photodetector may detect a fluctuation in laser power, which may be corrected by control of the laser. Hence, the control system 300 may be configured to control the radiation source 110 based on the related monitoring signal. In the depicted embodiment, the system 100 further comprise a functional generator 116 functionally coupled to the laser. The functional generator may be configured to have the laser modulate the measurement radiation, such as to perform the frequency sweep. The control system 300 may especially (also) control the functional generator 116.

[0136] Further, in the depicted embodiment, the system 100 comprises two lenses 190. In particular, the system 100 comprises a first lens 191 arranged upstream of the photoelectric detector 120 (and downstream of the polarizer 170). The first lens 191 may be configured to provide the (combined) radiation 111 to (all of) the pixels 125 of the photoelectric detector 120. The first lens 191 may especially be a cylindrical lens. The system 100 further comprises a second lens 192 arranged upstream of the second beam splitter 140,142 along the measurement path 10. The second lens 192 is configured to receive the measurement radiation 111 from the multimode fiber 130 and to provide the radiation to the second beam splitter 140,142.

[0137] Fig. 2A-F schematically depict the measurement path 10 near and in the sample 50, and how the measurement radiation 111 can travel through the same along different photon paths 112. In particular, Fig. 2A-2D schematically depict reflection geometries wherein the measurement path 10 enters the sample 50 at a first side 56 and exits the sample 50 at the first side 56. In contrast, Fig. 2E-2F depict transmission geometries wherein the measurement path 10 enters the sample 50 at a first side 56 and exits the sample 50 at a second side 57. Fig. 2A-B, E schematically depict embodiments wherein a multimode fiber 130 is arranged to receive the measurement radiation 111 as the measurement radiation 111 exits the sample 50 and to provide the measurement radiation to a second beam splitter 140,142 (via second lens 192). In Fig. 2C-D, F a second lens 192 is arranged to receive the measurement radiation 111 (directly) from the sample 50 and to provide the measurement radiation 111 to the second beam splitter 140, 142. As depicted in Fig. 2A-F the measurement path 10 enters the sample 50 along an entry (sub)path at the entry location 51 and exits the sample 50 along an exit (sub)path from an exit location 52. In the embodiments depicted in Fig. 2A, C, E-F the entry path and the exit path differ (at least) in sample location, i.e., the entry location and the exit location are separated by a distance du, such as a distance du selected from the range of 0.5 - 5 cm. In Fig. 2B and 2D the entry path and the exit path differ (at least) in path axis.]

[0138] In the embodiments depicted in Fig. 2C-D, F, the system 100, especially the hosting space 150, further comprises shielding 155 (or “light blocker 155”) configured to reduce, especially prevent, the detection of ambient light. The shielding may be used as an alternative to the multimode fiber 130. Hence, the radiation collection can be achieved by using a multimode fiber 130 (as shown in Fig.2A, Fig.2B, Fig.2E). The collected photons from the multimode fiber 130 are collimated by the second lens 192, and especially then focused by the first (cylindrical) lens 191 onto the photoelectric detector 120. Alternatively, the radiation collection can be achieved directly by the second lens 192 (as shown in Fig.2C, Fig.2D, Fig.2F), where the sample is covered by shielding 155. Hence, in embodiments, the system 100 comprises one or more of (a) a multimode fiber 130 configured to receive measurement radiation 111 from the hosting space 150, especially from the sample 50, and (b) shielding configured to block ambient light leaving the hosting space 150, especially ambient light leaving the sample 50.

[0139] Fig. 3 schematically depicts an embodiment of the method of the invention and of the operational mode of the system 100. In particular, in panel (a) Fig. 3 depicts providing the measurement radiation 111 along the measurement path 10 and along the reference path 20, wherein the measurement path 10 passes through the sample 50, and wherein the measurement path 10 and the reference path 20 merge into a combined path 30, wherein measurement radiation 111 traveling along the combined path 30 is detected using a photoelectric detector. Panel (b) of Fig. 3 schematically depicts the frequency of the measurement radiation 111, such as provided using a radiation source 110. In the depicted embodiment, the measurement radiation 111 comprises a plurality of measurement phases 40, wherein each measurement phase 40 has a (same) duration Tm, and wherein each measurement phase 40 comprises a frequency sweep 45. In each frequency sweep the frequency of the measurement radiation 40 is increased from a first frequency fl to a second frequency f2 and then returned to the first frequency fl. In particular, the frequency is first monotonically (and linearly) increased until the second frequency and then monotonically (and linearly) decreased until the first frequency. In the depicted embodiment, the frequency sweep thus has aA-shape. Panel (b) further schematically depicts the generation of the spectral signals Sm,n. In particular, panel (b) schematically depicts a plurality of images for each measurement phase 40 with intensity levels of each pixel 225 at that timepoint. Panels (c)-(g) schematically depict aspects of the determination of the material property based on the spectral signals Sm,n.

[0140] In embodiments, the material property may comprise a flow velocity at a material depth dm. In such embodiments, the method may comprise (i) subjecting the spectral signals (Sm,n), optionally following mean centering, to a Fourier transformation, and subsequently to squaring to provide power spectral densities Pm,n(See Fig. 3(c-d); (ii) selecting a time-of-flight frequency range TOFR based on a desired material depth (dm), e.g., based on different material layers (also see Fig. 3(a)). For instance, in Fig. 3(d), three TOFR are selected and indicated, where TOFRI includes signals from a first photon path 112i, TOFR2 includes signals from a second photon path 1122, and TOFR3 includes signals from a third photon path 112a; (iii) determining TOF-dependent energies Em,nin the power spectral densities Pm,nby integrating the power spectral densities Pm,nover the time-of-flight frequency range TOFR; (iv) determining spatial speckle contrasts Km(see Fig. 3(e)) based on the TOF-dependent energies Em,n; and determining the flow velocity based on the spatial speckle contrasts Km. Fig. 3(g) shows a doppler broadened DTOF, which is a function of flow velocities, ps’ and pa. In particular, the flow velocities can be measured by changing the modulation speed, i.e., by changing the measurement duration, and then ps’ and pacan be extracted by fitting the curve of Fig. 3(g).

[0141] In further embodiments, the material property may (further) comprise a reduced scattering coefficient ps’ and / or an absorption coefficient pa. In embodiments, the method may comprise determining the reduced scattering coefficient ps’ and the absorption coefficient pabased on the spectral signals Sm,n. In further embodiments, the method may comprise determining the flow velocity based on the correlation, the reduced scattering coefficient ps’ and the absorption coefficient pa.

[0142] Example of procedures

[0143] The approach of the invention may provide a Distribution of Time-Of-Flight (DTOF) that is Doppler broadened. To fit the Doppler broadened DTOF, the relative dynamics of different depths are determined first. In particular, a first procedure uses speckle contrast to determine relative dynamics, and the determined relative dynamics facilitate determining optical properties in the second procedure.

[0144] Procedure 1 - determination of flow velocity

[0145] Step 1 - Turn on radiation source 110 and photoelectric detector 120, and do not modulate the optical frequency, acquire N images with frame rate RD (with RD much faster than the decorrelation time of dynamic speckle). For each frame, calculate the (initial) speckle contrast Ksand the speckle number Ns:

[0146] < / (p)2> -< / (p) >2

[0147] K'=- ^77^ -

[0148]

[0149] where I(p) is the intensity of (radiation as detected by the) pthpixel, and < > denotes the average over all pixels 125. Due to the fast acquisition of the photoelectric detector 120, Ksis only related to speckle number Ns, rather than to the dynamics. Take average Nsover N images as collected speckle number. Step 2 - Modulate the optical frequency (fopt) of the measurement radiation in the range of 10 GHz to 1000 GHz with a ramp (i.e., I or \ or A) or sin waveform. The modulation speed, i.e. 1 / Tm, may, for instance, be selected from the range of 1 Hz to 1000 Hz. In particular, Tmmay be selected in view of the frame rate RD of the photoelectric detector 120, especially such that (f0+Δfopt / Tm*TOFmax) < RD / 2, where f0is the initial beat frequency due to path length difference between the measurement path and the reference path, where Δfoptis the difference between the lowest and the highest frequency in the frequency sweep, e.g., between the first frequency f1and the second frequency f2in the frequency sweep, and where TOF max is the maximum photon time of flight (TOF) in the sample.

[0150] Step 3 - For each measurement period 40, the camera acquires Ro*Tmframes of the image, i.e. images of the time course represented as I(p,t,k), where p is the pthpixel, t is the time, and k is the kthmeasurement phase.

[0151] Step 4 - For each pixel, subtract the mean value of I(p,t,k) (of all pixels) and obtain a mean centered signal Iac(p,t,k) (as shown in Fig. 3(c)).

[0152] Step 5 - Subject Iac(p,t,k) to Fourier transformation and square the result to obtain the power spectral density PSD(p,w,k), where w is the angular frequency.

[0153] Step 6 - Divide the power spectral density into multiple time-of-flight (TOF) windows (or “time-of-flight frequency ranges TOFR”) (as shown in Fig.3(d)), and integrate (the power spectral densities) in those windows to obtain the TOF-dependent energies E(p, TOF,k) (which is proportional to the photon number) in those TOF windows according to Parseval's theorem. The number of windows may be selected in view of the number of layers in a sample, and the window width may, for instance, be proportional to the layer depth.

[0154] Step 7 - Calculate the speckle contrast over all pixels to obtain TOF-dependent (effective) speckle contrasts Km(TOF,k):

[0155] < E(p, TOF, k)2> - < E(p, TOF, k) >2Km(TOF,k)2

[0156] Ns< E(p, TOF,k) >2

[0157] where < > denotes the mean value over all pixels (as shown in Fig.3(d)(e)). Step 8 - determine relative flow velocity changes based on (successive measurements of) Km.

[0158] Procedure 2 - determination of reduced scattering and absorption coefficients Due to the (relatively) slow modulation speed of the measurement radiation, the distribution of time-of-flight (DTOF) is broadened by the Doppler spectrum. In particular, if the modulation speed is high, in each measurement cycle, the dynamics are effectively frozen, thus the mentioned coefficient is decoupled with Doppler effect. However, with a slow modulation, the Doppler broadening effect also plays a role in the measured curve, which may facilitate determining the (Brownian) diffusion coefficient, the reduced scattering coefficient and the absorption coefficient from the same curve.

[0159] Step 1 - Change the modulation time τ (i.e., 1 / Tm) from τminHz to τmaxHz, and make sure that the maximum beat frequency (f0+Δfopt / τ*TOFmax) < RD / 2 to obtain modulation speed dependent speckle contrast K(TOF,k) (see procedure 1). In particular, the modulation time may be increased from τminto τmaxin a stepwise manner, especially with a constant step size.

[0160] Step 2 - Fit K(TOF,k,x) using the multiple-exposure speckle laser contrast equation:

[0161] exp(— 2cx) — 1 + 2cx exp(— 2cx) — 1 + 2cx

[0162] K (T OF, k,x) = a -2- + b -2- 2 (ex)22 (ex)2

[0163] where a = ρ²β(TOF)2, b = 4ρ²β(TOF)[1-β(TOF)], C=1 / TC(TOF), p is a normalization factor to account for speckle averaging effects, ^(TOF) is the proportion of dynamic scattering in (all) scattering events, and TC(TOF) is the speckle correlation time of the speckles with certain TOF:

[0164] TC(TOF) = [formula - see image]

[0165]

[0166] where v is the wavenumber, DB(TOF) is the TOF-dependent (Brownian) diffusion coefficient, ps' is the reduced scattering coefficient, v = C / UR, C is the speed of light in vacuum, and nR is the refractive index of the medium. In particular, DB(TOF) may be an indicator of an absolute flow rate.

[0167] Step 3 - Choose a fixed modulation time in the range of τmin- τmax, average PSD(p,w,k) over all pixels to obtain a PSD(w,k) curve (as shown in Fig.3(f)), where PSD(w,k)=f(ps',pa, Tc(TOF),w), where ps' is the reduced scattering coefficient, and pais the absorption coefficient. In particular, previously obtained measurement data matching the selected fixed modulation time may be used hereafter. Alternatively, new measurements with the selected fixed modulation time may be performed.

[0168] Step 4 - Calculate the TOF-dependent doppler spectrum width Cs(w):

[0169] 1 / TC(w), (0 < w < w0)

[0170]

[0171] (1 / TC(W), (W0< w < wmax)

[0172] where wmaxis the maximum angular frequency (=7TRD), wo=27tfo, TC(W) is interpolated from TC(TOF) using cubic spline, and TOF can be transformed to w by: w = 2π(Δfopt / Tm)TOF + 2πf0= γTOF + w0

[0173]

[0174] Step 5 - Fit the P(w,k) curve with following equation to extract ps’ and pa:

[0175] fWm“%2Cs(w)

[0176] P(w, k) = I 7— — - - - ^dwt

[0177]

[0178] JotJC2(w) + (w - wt)2 [where wt is the angular frequency in the integration, which is used to distinguish from w,

[0179] and where, for a transmission geometry:

[0180] exp(-pav^)Bt(Wt) P2f(wt) = -7[ e*P( - W7- 47T£)V(^)2J4TT£)V^04Dv — Y where \..r-(d - z_m)2^ 5t(wt) = {(d - z+m)exp[-ZW+mr ^ ] (dz-m)exP[ Wft- m 4Dv — 4Dv —

[0181]

[0182] =-co Y Y z+m= 2m(d + 2ze) + z0

[0183] z_m= 2m(d + 2ze) — 2ze— z0

[0184] D = 1 / 3 ( / / a+ ps’)

[0185] 1

[0186] z° = 7

[0187] 'S

[0188] ze= 2AD

[0189] 1 + R(n) 1 - / ?(n) R(n) = -1.43997T2+ 0.70997T1+ 0.6681 + 0.0636n and where for a reflectance geometry: exp(- / / av^)Br(wt)cp+^ f(Wt) = -r[ exp (( -p2W ■ r- 4TT£)V(^)2J47T£)V^p-“T 4Dv — Y where -z7uo2(zo + 2ze)2Br(wt) = zoexp( -. w-t) + (z0+ 2ze)exp[ - ^7— -] 4Dv — 4Dv —

[0190]

[0191] Y Y It will be clear to the person skilled in the art that above-described procedures 1 and 2 are specific detailed examples and that modifications can be made without deviating from the general concept of the invention as outlined herein. For instance, the skilled person may use high-pass filtering instead of mean centering, and replace the specific PDS computation with an alternative PSD estimator, such as following the Welch method. Similarly, the skilled person may use alternative speckle contrast expressions and / or alternative diffusionapproximation formulations.

[0192] Experiment 1

[0193] Fig. 4A-B schematically depict experimental results corresponding to abovedescribed first procedure. The measurement duration Tmwas set at 0.01 s (or “the modulation frequency was 100 Hz”), and the photoelectric detector 120 was configured to operate at a frame rate RD of 100 kHz, i.e., RD*TM was set at 1000. An m*nj array 122 comprising a total of 4096 pixels 125 (ni=256; nj=16) was used for data acquisition, i.e., n = 4096. The samples 50 consisted of an 11 mm thick cuvette filled with water and 20% intralipid emulsion at varying concentrations (1%, 2%, 3%, and 4%). The measurements were performed in transmission geometry as schematically depicted in Fig. 2F. 10000 frames were captured for each sample 50.

[0194] The left side of Fig. 4A schematically depicts the measured photoelectron charge Cp for each pixel 125 in the ni*nj array 122 for each frame index Fi in the 10000 frames for one of the samples 50. The right side of Fig. 4A schematically depicts the photoelectron charge Cp(in a.u.) over time T in seconds for a single pixel 125. In particular, the right side of Fig. 4A schematically depicts the photoelectric charge over a plurality of the m measurement phases. Hence, Fig. 4A schematically depicts the spectral signals Sm,n for all pixels on the left side and for a single pixel on the right side.

[0195] Each sample 50 was analyzed separately according to the following procedure. For each pixel 125, the mean value of the time course (Fig. 4B; right side) was subtracted, the resulting signal was subjected to a Fast Fourier Transform (FFT), and was subsequently squared to obtain the power spectral density Pm,n for each pixel, i.e., the spectral signals S m,n were mean centered, subsequently subjected to a Fourier transformation, and were subsequently squared to provide the power spectral densities Pm,n.

[0196] Averages of the power spectral densities Pm,n over all pixels are shown in Fig.

[0197] 4B. Specifically, Fig. 4B depicts (normalized) amplitude A against angular frequency co (in radians / second) for the four samples 50. Specifically, line Li corresponds to the sample containing 1% of the intralipid emulsion, line L2 corresponds to the sample containing 2% of the intralipid emulsion, line L3 corresponds to the sample containing 3% of the intralipid emulsion, and line L4 corresponds to the sample containing 4% of the intralipid emulsion. A set of bandpass filters was applied to the power spectral densities Pm,n for each pixel 125 and band-specific information was extracted from which the speckle contrast was computed, i.e., average energies Em,n in the power spectral densities Pm,n were determined by integrating the power spectral densities Pm,n over three different time-of-flight frequency ranges TOFR (as schematically represented in Fig. 4B), and the spatial speckle contrasts Kmwere determined based on the average energies Em,n. A summary of the reduced scattering coefficients ps’, the absorption coefficients paand the determined spatial speckle contrasts Kmis provided in the following table:

[0198] Sample Ps’ [nr1] pa[nr1] Kmfor different central TOF values

[0199] TOF =167 ps TOF = 667 ps TOF = 1500 ps 1 176.4 2.5 0.0369 0.0343 0.0285 2 352.8 5 0.0347 0.0328 0.0298 3 529.8 7.5 0.0465 0.0447 0.0431 4 705.6 10 0.0349 0.0328 0.0315

[0200]

[0201] The TOF values presented in the table above correspond to the central points in the corresponding TOF ranges; the central values are used as indicators as TOF filters may be broadened by Doppler shifts.

[0202] The determined spatial speckle contrasts Kmrevealed a decreasing trend with increasing time-of-flight (TOF) values, indicating that photons with longer TOF undergo faster dynamics.

[0203] Experiment 2

[0204] Static samples were fabricated from polydimethylsiloxane (PDMS) mixed with titanium dioxide (TiO2) as the scattering agent and carbon powder (CP) as the absorber. The samples had a uniform thickness of 10 mm and were mounted in the measurement path for measurements in a transmission geometry, with illumination and detection positioned on opposite sides of the sample with zero source-detection separation. These samples followed established formulations for tuning optical properties as described in GOLDFAIN et al., Polydimethyl siloxane tissue-mimicking phantoms with tunable optical properties, Journal of Biomedical Optics, Vol. 27, Issue 7, 2021; the parameters determined using the method of the invention were compared with the parameters in this reference article (see below).

[0205] Measurements and analyses were performed in line with procedure 2 as described above. Specifically, the determined DTOF curves were fitted using the equations in step 5 of procedure 2, specifically using the appropriate equation starting with “ / (wt)” given the (transmission or reflectance) geometry of the measurement setup, convolved with a separately determined instrument response function (IRF) acquired without a sample. The extracted psand pawere found to be in good agreement with the previously determined values as reported in the reference article. The following table summarizes the results obtained with samples with varying TiCh concentration, resulting in varying reduced scattering coefficients ps’

[0206] Concentration TiCh (%o) ps’ (GOLDFAIN et al.) (m1) ps’ (this work) (m-1) 0.35 581 563 ± 11.3 0.40 664 661 ± 11.9 0.45 748 741 ± 12.7 0.50 830 836±9.2 0.55 913 872±8.0 0.60 996 1022± 11.1

[0207]

[0208] The following table summarizes the results obtained with samples with a fixer TiCh-concetration of 0.60 %o, and a varying concentration of CP, resulting in varying absorption coefficients pa:

[0209] Concentration CP (%o) pa(GOLDFAIN et al.) (m1) pa(this work) (m-1) 0.00 0 0 0.016 12.3 13 0.033 24.6 24 0.050 37 35

[0210]

[0211] Experiment 3

[0212] Fig. 5A schematically depicts a two-layer tissue-mimicking sample 50 comprising an static layer 53 (top layer) and a dynamic layer 54 (bottom layer). The static layer 53 comprises static scatterers, while the dynamic layer 54 comprises dynamic scatterers driven by a syringe pump 154 with a pulsatile profile schematically depicted above the syringe pump 154 (pump modulation frequency set at 0.5 Hz). For visualizational purposes, the measurement path 10 and the reference path 20 are depicted to separately arrive at the photoelectric detector 120. However, in practice, the measurement path and the reference path 20 merge into a combined path upstream of the photoelectric detector 120.

[0213] The static layer 53 was fabricated following the procedure described in Experiment 2 and contains 0.6%o TiCh and 0.033%o CP, with a total thickness of 5 mm. The dynamic layer 54 consists of a mixture of Intralipid 20% and deionized water at a final concentration of 5% Intralipid. The pump is modulated at 0.5 Hz and delivers 0.1 mL of fluid per step.

[0214] Measurements and analyses were performed in line with procedure 1 as described above. Specifically, photons with a longer ToF accumulated a larger fraction of their partial path length in the deeper dynamic layer, resulting in faster temporal decorrelation. By averaging the PSD across all camera pixels, a Doppler-broadened DTOF was obtained, as shown in Fig. 5B. Specifically, Fig. 5B depicts the amplitude A (in a.u.) of the PSD vs. frequency f (in kHz). Here, the amplitude A of the PSD tail may be observed to be higher than the starting point as the top layer is static and does not result in Doppler spectrum accumulation. To probe depth-dependent dynamics, a series of bandpass filters was applied to the PSD of each pixel to calculate the speckle contrast. The acquisition window was set to T = 0.1 s, corresponding to a measurement rate of 10 Hz. All BP filters shared the same upper cut-off frequency ( / up= 40 kHz) but differed in their lower cut-off frequency ( low), such that filters with higher iowpreferentially selected photons with longer ToFs, i.e., photons that on average went deeper into the sample.

[0215] Fig. 5C schematically depicts that the mean speckle contrast < Km2>first increases slightly as iowis increased up to / u. This behavior may indicate that Doppler spectrum leakage from the deep layer vanishes below u: photons in this range do not carry dynamic information; the noise may remain (essentially) constant, while the mean intensity decreases due to the narrowing filter bandwidth. Beyond / u, further increasing iowreduces the contribution from static photons in the superficial layer, leading to a higher effective speckle contrast, i.e., leading to a lower Km. After 12, the contrast predominantly corresponds to photons from the dynamic second layer and therefore decreases only gradually. These results demonstrate that the method of the invention can distinguish between static and dynamic layers, and that the analysis can be focused on the dynamic layers by the selection of a suitable bandpass filter.

[0216] Fig. 5D schematically depicts amplitude A (in a.u.) vs. frequency f (in Hz) as obtained via a Fourier transformation of the temporal fluctuation in speckle contrast (for fiow=12.5 kHz), indicating that the deep-weighted filter bands capture the periodic modulation induced by the syringe pump, and that the pump modulation frequency of 0.5 Hz imposed by the syringe pump can be recovered via the Fourier transformation. These results demonstrate that the method of the invention is sensitive to pulsatile flow, and can identify the rhythm of a pulsatile flow. The term “plurality” refers to two or more. Furthermore, the terms “a plurality of’ and “a number of’ may be used interchangeably.

[0217] The terms “substantially” or “essentially” herein, and similar terms, will be understood by the person skilled in the art. The terms “substantially” or “essentially” may also include embodiments with “entirely”, “completely”, “all”, etc. Hence, in embodiments the adjective substantially or essentially may also be removed. Where applicable, the term “substantially” or the term “essentially” may also relate to 90% or higher, such as 95% or higher, especially 99% or higher, even more especially 99.5% or higher, including 100%. Moreover, the terms ’’about” and “approximately” may also relate to 90% or higher, such as 95% or higher, especially 99% or higher, even more especially 99.5% or higher, including 100%. For numerical values it is to be understood that the terms “substantially”, “essentially”, “about”, and “approximately” may also relate to the range of 90% - 110%, such as 95%-105%, especially 99%-l 01% of the values(s) it refers to.

[0218] The term “comprise” also includes embodiments wherein the term “comprises” means “consists of’.

[0219] The term “and / or” especially relates to one or more of the items mentioned before and after “and / or”. For instance, a phrase “item 1 and / or item 2” and similar phrases may relate to one or more of item 1 and item 2. The term "comprising" may in an embodiment refer to "consisting of but may in another embodiment also refer to "containing at least the defined species and optionally one or more other species".

[0220] Furthermore, the terms first, second, third and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein.

[0221] The devices, apparatus, or systems may herein amongst others be described during operation. As will be clear to the person skilled in the art, the invention is not limited to methods of operation, or devices, apparatus, or systems in operation.

[0222] The term “further embodiment” and similar terms may refer to an embodiment comprising the features of the previously discussed embodiment, but may also refer to an alternative embodiment.

[0223] It should be noted that the above-mentioned embodiments illustrate rather than limit the invention, and that those skilled in the art will be able to design many alternative embodiments without departing from the scope of the appended claims. In the claims, any reference signs placed between parentheses shall not be construed as limiting the claim.

[0224] Use of the verb "to comprise" and its conjugations does not exclude the presence of elements or steps other than those stated in a claim. Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising”, “include”, “including”, “contain”, “containing” and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.

[0225] The article "a" or "an" preceding an element does not exclude the presence of a plurality of such elements.

[0226] The invention may be implemented by means of hardware comprising several distinct elements, and by means of a suitably programmed computer. In a device claim, or an apparatus claim, or a system claim, enumerating several means, several of these means may be embodied by one and the same item of hardware. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.

[0227] The invention also provides a control system that may control the device, apparatus, or system, or that may execute the herein described method or process. Yet further, the invention also provides a computer program product, when running on a computer which is functionally coupled to or comprised by the device, apparatus, or system, controls one or more controllable elements of such device, apparatus, or system.

[0228] The invention further applies to a device, apparatus, or system comprising one or more of the characterizing features described in the description and / or shown in the attached drawings. The invention further pertains to a method or process comprising one or more of the characterizing features described in the description and / or shown in the attached drawings. Moreover, if a method or an embodiment of the method is described being executed in a device, apparatus, or system, it will be understood that the device, apparatus, or system is suitable for or configured for (executing) the method or the embodiment of the method, respectively.

[0229] The various aspects discussed in this patent can be combined in order to provide additional advantages. Further, the person skilled in the art will understand that embodiments can be combined, and that also more than two embodiments can be combined. Furthermore, some of the features can form the basis for one or more divisional applications.

Claims

1. CLAIMS:

1. A method for determining a material property of a sample (50) using a photoelectric detector (120), wherein the photoelectric detector (120) has a frame rate RD and comprises an array (122) comprising n pixels (125), wherein the frame rate RD > 10 kHz, wherein n > 100, and wherein the method comprises:3.providing measurement radiation (111) along a measurement path (10) and along a reference path (20), wherein the measurement radiation (111) is coherent, wherein the measurement radiation (111) comprises m measurement phases (40), wherein m > 2, wherein the measurement phases (40) have a measurement duration (Tm), wherein RD*Tm> 100, wherein each measurement phase (40) comprises a frequency sweep (45) over a frequency range selected from the range of 10 - 1000 GHz, wherein the measurement path (10) enters the sample (50) at an entrance location (51), passes through at least part of the sample (50), and exits the sample (50) at an exit location (52), wherein the entrance location (51) and the exit location (52) are separated by at most 5 cm, wherein the measurement path (10) downstream of the sample (50) differs from the measurement path (10) upstream of the sample (50), and wherein the measurement path (10) and the reference path (20) merge into a combined path (30) downstream of the sample (50);4.detecting a spectral interference pattern of the measurement radiation (111) travelling along the combined path (30) using the photoelectric detector (120) to provide a spectral signal (Sm,n) for each of the m measurement phases (40) and the n pixels (125); and determining the material property based on the spectral signals (Sm,n).

2. The method according to claim 1, wherein the material property comprises a flow velocity at a material depth (dm), wherein the method further comprises:6.selecting a time-of-flight frequency range TOFR based on the material depth (dm);7.subj ecting the spectral signal s (Sm,n) to F ourier transformation, and subsequently to squaring to provide power spectral densities Pm,n;8.determining TOF-dependent energies Em,nin the power spectral densities Pm,nby integrating the power spectral densities Pm,nover the time-of-flight frequency range TOFR;9.determining spatial speckle contrasts Kmbased on the TOF-dependent energies Em,n; and determining the flow velocity based on the spatial speckle contrasts Km.

3. The method according to any one of the preceding claims, wherein the frame rate RD is selected from the range of 100 kHz - 2 MHz.

4. The method according to any one of the preceding claims, wherein n > 1000.

5. The method according to any one of the preceding claims, wherein Tm> 0.001 s.

6. The method according to any one of the preceding claims, wherein the frequency sweep comprises sweeping from a first frequency (fl) to a second frequency (f2), wherein fi and fi differ by at least 10 GHz.

7. The method according to claim 6, wherein the frequency sweep (45) comprises a linear frequency sweep (46).

8. The method according to any one of the preceding claims 2-7, wherein the material property further comprises a reduced scattering coefficient (ps’), and an absorption coefficient (pa), wherein the method comprises performing a second measurement comprising:16.providing second measurement radiation along the measurement path (10) and along the reference path (20), wherein the second measurement radiation is coherent, wherein the second measurement radiation comprises m2 second measurement phases, wherein m2 > 2, wherein second measurement durations (Tnu) of the second measurement phases are varied between a minimum measurement duration (Tmin) and a maximum measurement duration (Tmax), wherein for each second measurement phase applies that Ro*Tm2 > 100, wherein each second measurement phase comprises a second frequency sweep over a frequency range selected from the range of 10 - 1000 GHz;17.detecting a second spectral interference pattern of the second measurement radiation (111) travelling along the combined path (30) using the photoelectric detector (120) to provide a second spectral signal (Sm2,n) for each of the m2 measurement phases and the n pixels (125);18.subjecting the second spectral signals (Sm2,n) to Fourier transformation, and subsequently to squaring to provide second power spectral densities Pm2,n; determining second TOF-dependent energies Em2,nin the second power spectral densities Pm2,n by integrating the second power spectral densities Pm2,n over the time-of-flight frequency range TOFR;19.determining second spatial speckle contrasts Km2 based on the second TOF-dependent energies Em2,n;20.determining TOF-dependent speckle correlation times TCbased on the second spatial speckle contrasts Km2; and21.determining the reduced scattering coefficient (ps’), and the absorption coefficient (pa) based on the TOF-dependent speckle correlation times TCand one or more of the power spectral densities Pm,n and the second power spectral densities Pm2,n.

9. A system (100) comprising a radiation source (110), a photoelectric detector (120), a hosting space (150), and a control system (300), wherein the radiation source (110) comprises a swept laser source (115), wherein the photoelectric detector (120) has a frame rate RD and comprises an array (122) comprising n pixels (125), wherein the frame rate RD > 10 kHz, and wherein n > 100, wherein the radiation source (110) is configured to provide measurement radiation (111) to the photoelectric detector (120) via a measurement path (10) and via a reference path (20), wherein the measurement radiation (111) is coherent, wherein the measurement path (10) passes through the hosting space (150), wherein the measurement path (10) upstream of the hosting space (150) differs from the measurement path downstream of the hosting space (150), and wherein the measurement path (10) and the reference path (20) merge into a combined path (30) downstream of the hosting space (150) and upstream of the photoelectric detector (120), wherein the control system (300) is configured to execute an operational mode, wherein in the operational mode:23.the hosting space (150) is configured to host a sample (50);24.the radiation source (110) is configured to provide the measurement radiation (111), wherein the measurement radiation (111) comprises m measurement phases (40), wherein m > 2, wherein the measurement phases (40) have a measurement duration (Tm), wherein Ro*Tm > 100, wherein each measurement phase (40) comprises a frequency sweep (45) over a frequency range selected from the range of 10 - 1000 GHz; and25.the photoelectric detector (120) is configured to detect a spectral interference pattern of the measurement radiation (111) travelling along the combined path (30) to provide a spectral signal (Sm,n) for each of the m measurement phases (40) and the n pixels (125), and to provide the spectral signals (Sm,n) to the control system (300).

10. The system (100) according to claim 9, wherein the operational mode further comprises:26.the control system (300) determining a material property of the sample (50) based on the spectral signals (Sm,n).

11. The system (100) according to claim 10, wherein the material property comprises a flow velocity at a material depth (dm), wherein the operational mode further comprises:28.the control system (300) selecting a time-of-flight frequency range TOFR based on the material depth (dm);29.the control system (300) subjecting each spectral signal (Sm,n) to a Fourier transformation, and subsequently to squaring to provide power spectral densities Pm,n;30.the control system (300) determining TOF-dependent energies Em,nin the power spectral densities Pm,nby integrating the power spectral densities Pm,nover the time-of-flight frequency range TOFR;31.the control system (300) determining spatial speckle contrasts Kmbased on the TOF-dependent energies Em,n;32.the control system (300) determining a correlation of the spatial speckle contrast Kmover the measurement phases (40); and33.the control system (300) determining the flow velocity based on the correlation.

12. The system (100) according to any one of the preceding claims 9-11, wherein the system (100) further comprises a multimode fiber (130), wherein the multimode fiber (130) provides at least part of the measurement path (10) between the hosting space (150) and the photoelectric detector (120).

13. The system (100) according to claim 12, wherein the radiation source (110) is configured to provide the measurement radiation (111) to a hosting space entry location (151), and wherein the multimode fibers (130) are configured to receive the measurement radiation (111) from a hosting space exit location (152), wherein the hosting space entry location (151) and the hosting space exit location (152) are separated by at most 5 cm.

14. The system (100) according to any one of the preceding claims 9-13, wherein the system (100) further comprises a polarization rotator (160) and a polarizer (170), wherein the polarization rotator (160) is arranged in the reference path (20), wherein the control system (300) is configured to control a polarization state of the measurement radiation (111) traveling along the reference path (20) by controlling the polarization rotator (160), and wherein the polarizer (170) is arranged in the combined path (30).

15. The system (100) according to any one of the preceding claims 9-14, wherein the system (100) comprises a beam splitter (140) and a photodetector (180), wherein the beam splitter (140) is arranged within the reference path (20), wherein the beam splitter (140) is configured to split off part of the measurement radiation (111) to the photodetector (180), wherein the photodetector (180) is configured to monitor one or more optical properties of the measurement radiation (111) and to provide a related monitoring signal to the control system (300), wherein the control system (300) is configured to control the radiation source (110) based on the related monitoring signal.

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