This review is aimed at presenting the state-of-the-art of time domain (TD) functional near-infrared spectroscopy (fNIRS). We first introduce the physical principles, the basics of modeling and data analysis. Basic instrumentation components (light sources, detection techniques, and delivery and collection systems) of a TD fNIRS system are described. A survey of past, existing and next generation TD fNIRS systems used for research and clinical studies is presented. Performance assessment of TD fNIRS systems and standardization issues are also discussed. Main strengths and weakness of TD fNIRS are highlighted, also in comparison with continuous wave (CW) fNIRS. Issues like quantification of the hemodynamic response, penetration depth, depth selectivity, spatial resolution and contrast-to-noise ratio are critically examined, with the help of experimental results performed on phantoms or in vivo. Finally we give an account on the technological developments that would pave the way for a broader use of TD fNIRS in the neuroimaging community.

In biomedical optics, the characterization of instrumentation with the help of appropriate tissue-simulating phantoms¹ plays an important role, ranging from proof-of-principle tests at early stages of the development to quality assurance during routine clinical application.² Numerous performance studies have been carried out by individual research groups; however, there are only a few multilaboratory efforts to characterize and to compare multiple instruments. Such approaches are essential to provide a sound basis for achieving quantitatively comparable results in clinical studies. They require the development of standardized guidelines to perform the same measurements on phantoms with the same properties in different laboratories. In the field of photon migration instruments, the first systematic study of different instruments was performed on the basis of the MEDPHOT protocol.³ Recently, the development and testing of phantoms has been reported for quality assurance in a multicenter clinical trial to measure the response of breast tumors to neoadjuvant chemotherapy by means of diffuse optical spectroscopic imaging.⁴ In the context of fluorescence imaging of tissues, phantoms were developed to characterize and compare imaging systems and to train surgeons.⁵

A method for the discrimination of superficial and deep absorption variations by time domain functional near infrared spectroscopy is presented. The method exploits the estimate of the photon time-dependent pathlength in different domains of the sampled medium and makes use of an approach based on time-gating of the photon distribution of time-of-flights. Validation of the method is performed in the two-layer geometry to focus on muscle and head applications. Numerical simulations varied the thickness of the upper layer, the interfiber distance, the shape of the instrument response function and the photon counts. Preliminary results from in vivo data are also shown.

We have designed a compact dual wavelength (687 nm, 826 nm) multi-channel (16 sources, 8 detectors) medical device for muscle and brain imaging based on time domain functional near infrared spectroscopy. The system employs the wavelength space multiplexing approach to reduce wavelength cross-talk and increase signal-to-noise ratio. System performances have been tested on homogeneous and heterogeneous tissue phantoms following specifically designed protocols for photon migration instruments. Preliminary in vivo measurements have been performed to validate the instrument capability to monitor hemodynamic parameters changes in the arm muscle during arterial occlusion and in the adult head during a motor task experiment.

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O₂Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O₂Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O₂Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

Diffuse optics¹ provides noninvasive tools to investigate highly scattering media (e.g., biological tissues in the wavelength range from 600 to 1300 nm) of large volumes (cubic centimeters) and depths up to a few centimeters beneath the surface. Both chemical (related to absorption) and structural (related to scattering) information can be retrieved by photons traveling through the diffusive medium. Numerous applications have been pursued, both in the medical field—ranging from functional brain imaging^2,3 and neuromonitoring,⁴ 5. ^{– 6} to cancer diagnostics^7,8 and therapy monitoring,^9,10—and in industrial sectors such as characterization of food,^11,12 wood,^13,14 and pharmaceuticals.^15,16 A key requirement for such applications to grow and gain a more widespread clinical or industrial acceptance is to achieve a high grade of reliability, reproducibility, accuracy in quantification, and comparability of clinical results.¹⁷ There is a compelling need to nurture the culture of quality assessment and quantitative grading of instruments in diffuse optics to support the parallel development of new instruments/techniques and applications on a stringent basis.¹⁸ 19. ^{– 20}