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Monitoring of human tissue hemodynamics is invaluable in clinics as the proper blood flow regulates cellular-level metabolism. Time-domain diffuse correlation spectroscopy (TD-DCS) enables noninvasive blood flow measurements by analyzing temporal intensity fluctuations of the scattered light. With time-of-flight (TOF) resolution, TD-DCS should decompose the blood flow at different sample depths. For example, in the human head, it allows us to distinguish blood flows in the scalp, skull, or cortex. However, the tissues are typically polydisperse. So photons with a similar TOF can be scattered from structures that move at different speeds. Here, we introduce a novel approach that takes this problem into account and allows us to quantify the TOF-resolved blood flow of human tissue accurately. We apply this approach to monitor the blood flow index in the human forearm in vivo during the cuff occlusion challenge. We detect depth-dependent reactive hyperemia. Finally, we applied a controllable pressure to the human forehead in vivo to demonstrate that our approach can separate superficial from the deep blood flow. Our results can be beneficial for neuroimaging sensing applications that require short interoptode separation.

We developed and applied parallel interferometric near-infrared spectroscopy (NIRS) for rapid cerebral blood flow and absorption monitoring. By operating ~100-500x faster than competing optical techniques, we can monitor prefrontal cortex activation in humans in vivo.

SIGNIFICANCE: Multi-laboratory initiatives are essential in performance assessment and standardization-crucial for bringing biophotonics to mature clinical use-to establish protocols and develop reference tissue phantoms that all will allow universal instrument comparison. AIM: The largest multi-laboratory comparison of performance assessment in near-infrared diffuse optics is presented, involving 28 instruments and 12 institutions on a total of eight experiments based on three consolidated protocols (BIP, MEDPHOT, and NEUROPT) as implemented on three kits of tissue phantoms. A total of 20 synthetic indicators were extracted from the dataset, some of them defined here anew. APPROACH: The exercise stems from the Innovative Training Network BitMap funded by the European Commission and expanded to include other European laboratories. A large variety of diffuse optics instruments were considered, based on different approaches (time domain/frequency domain/continuous wave), at various stages of maturity and designed for different applications (e.g., oximetry, spectroscopy, and imaging). RESULTS: This study highlights a substantial difference in hardware performances (e.g., nine decades in responsivity, four decades in dark count rate, and one decade in temporal resolution). Agreement in the estimates of homogeneous optical properties was within 12% of the median value for half of the systems, with a temporal stability of

Interferometric near-infrared spectroscopy (iNIRS) is an optical method that noninvasively measures the optical and dynamic properties of the human brain in vivo. However, the original iNIRS technique uses single-mode fibers for light collection, which reduces the detected light throughput. The reduced light throughput is compensated by the relatively long measurement or integration times (∼1 sec), which preclude monitoring of rapid blood flow changes that could be linked to neural activation. Here, we propose parallel interferometric near-infrared spectroscopy (πNIRS) to overcome this limitation. In πNIRS we use multi-mode fibers for light collection and a high-speed, two-dimensional camera for light detection. Each camera pixel acts effectively as a single iNIRS channel. So, the processed signals from each pixel are spatially averaged to reduce the overall integration time. Moreover, interferometric detection provides us with the unique capability of accessing complex information (amplitude and phase) about the light remitted from the sample, which with more than 8000 parallel channels, enabled us to sense the cerebral blood flow with only a 10 msec integration time (∼100x faster than conventional iNIRS). In this report, we have described the theoretical foundations and possible ways to implement πNIRS. Then, we developed a prototype continuous wave (CW) πNIRS system and validated it in liquid phantoms. We used our CW πNIRS to monitor the pulsatile blood flow in a human forearm in vivo. Finally, we demonstrated that CW πNIRS could monitor activation of the prefrontal cortex by recording the change in blood flow in the forehead of the subject while he was reading an unknown text.

Time-domain diffuse optics exploits near infrared light pulses diffused in turbid samples to retrieve their optical properties e.g., absorption and reduced scattering coefficients. Typically, interference effect are discarded, but speckle effects are exploited in other techniques e.g., diffuse correlation spectroscopy (DCS) to retrieve information regarding the tissue dynamics. Here, using a highly coherent Ti:Sapphire mode-locked laser and a single-mode detection fiber, we report the direct observation of temporal fluctuations in the measured distribution of time-of-flights (DTOF) curve. We study the dependence of these fluctuations on the sample dynamical properties (moving from fluid to rigid tissue-mimicking phantoms) and on the area of the detection fiber, which is directly linked to the number of collected coherence areas. Our observation agree with a time-resolved speckle pattern, and may enable the simultaneous monitoring of the tissue optical and dynamical properties.

We utilized time-domain diffuse correlation spectroscopy (TD-DCS) to quantify depth-resolved blood flow changes for in vivo experiments on arm and forehead adult humans. We illustrated that conventional TD-DCS processing is incapable of estimating blood flow changes at short source-detector separations, as expected. To tackle this problem, we introduced a novel model. We recovered the relative blood flow index of the forearm muscle during the cuff occlusion challenge and human forehead under variable pressure accurately.

Performance assessment and standardization are indispensable for instruments of clinical relevance in general and clinical instrumentation based on photon migration/diffuse optics in particular. In this direction, a multi-laboratory exercise was initiated with the aim of assessing and comparing their performances. 29 diffuse optical instruments belonging to 11 partner institutions of a European level Marie Curie Consortium BitMap1 were considered for this exercise. The enrolled instruments covered different approaches (continuous wave, CW; frequency domain, FD; time domain, TD and spatial frequency domain imaging, SFDI) and applications (e.g. mammography, oximetry, functional imaging, tissue spectroscopy). 10 different tests from 3 well-accepted protocols, namely, the MEDPHOT2 , the BIP3 , and the nEUROPt4 protocols were chosen for the exercise and the necessary phantoms kits were circulated across labs and institutions enrolled in the study. A brief outline of the methodology of the exercise is presented here. Mainly, the design of some of the synthetic descriptors, (single numeric values used to summarize the result of a test and facilitate comparison between instruments) for some of the tests will be discussed.. Future actions of the exercise aim at deploying these measurements onto an open data repository and investigating common analysis tools for the whole dataset.

Hybrid device for the study of blood flow index and hemoglobins concentrations changes was developed. Diffuse correlation spectroscopy and time-resolved near-infrared spectroscopy were applied to study brain hemodynamics of healthy adults human during the Valsalva maneuver.

We apply time-domain diffuse correlation spectroscopy (TD DCS) to quantify dynamics in samples with mixed dynamics, containing both static and dynamic scatterers. We demonstrate that standard TD DCS processing is incapable to properly quantify dynamics at short source-detector distances due to the strong influence of the static component. To solve this problem, we introduce a novel model, which allows recovering the autocorrelation decay of the dynamic part properly. We then apply this novel approach in humans in vivo. We recovered the blood flow index of the leg muscle covered by the thin static turbid layer during the cuff occlusion challenge.

A multi-laboratory exercise, involving 29 diffuse optical instruments, aimed at performance assessment of diffuse optics instruments on standardized protocols is presented. The overarching methodology and future actions will also be discussed.

Performance assessment of instruments is a growing demand in the diffuse optics community and there is a definite need to get together to address this issue. Within the EU Network BITMAP1, we initiated a campaign for the performance evaluation of 10 diffuse optical instrumentation from 7 partner institutions adopting a set of 3 well accepted, standardized protocols. A preliminary analysis of the outcome along with future perspectives will be presented.

Near infrared light pulses, multiply scattered by random media, carry useful information regarding the sample key constituents and their microstructures. Usually, the photon diffusion equation is used to interpret the data, which neglects any interference effect in the detected light fields. However, in several experimental techniques, such as diffuse correlation spectroscopy or laser speckle flowmetry, the effect of light coherence is exploited to retrieve the information on the sample dynamical properties. Here, using an actively mode-locked Ti:Sapphire laser, we report the observation of temporal fluctuations in the diffused light pulse, which cannot be described by the diffusion theory. We demonstrate the sensitivity of these fluctuations on the sample dynamical properties and on the number of detected coherence areas (i.e., speckles). In addition, after interpreting the effect as a time-resolved speckle pattern, we propose a simple statistical method for its quantification. The proposed approach may enable the simultaneous monitoring of the static (absorption and scattering coefficients) and dynamical (Brownian diffusion coefficient) properties of the sample, and also provide physical insight on the propagation of optical waves in random media.

Time-resolved diffuse correlation spectroscopy makes the potential to measure blood flow at different tissue layers. We developed an instrument based on a commercial laser module, and validated its sensitivity to particle movements at different depths.