Near-infrared spectroscopy (NIRS) is an optical technique that can measure brain tissue oxygenation and haemodynamics in real-time and at the patient bedside allowing medical doctors to access important physiological information. However, despite this, the use of NIRS in a clinical environment is hindered due to limitations, such as poor reproducibility, lack of depth sensitivity and poor brain-specificity. Time domain NIRS (or TD-NIRS) can resolve these issues and offer detailed information of the optical properties of the tissue, allowing better physiological information to be retrieved. This is achieved at the cost of increased instrument complexity, operation complexity and price. In this review, we focus on brain monitoring clinical applications of TD-NIRS. A total of 52 publications were identified, spanning the fields of neonatal imaging, stroke assessment, traumatic brain injury (TBI) assessment, brain death assessment, psychiatry, peroperative care, neuronal disorders assessment and communication with patient with locked-in syndrome. In all the publications, the advantages of the TD-NIRS measurement to (1) extract absolute values of haemoglobin concentration and tissue oxygen saturation, (2) assess the reduced scattering coefficient, and (3) separate between extra-cerebral and cerebral tissues, are highlighted; and emphasize the utility of TD-NIRS in a clinical context. In the last sections of this review, we explore the recent developments of TD-NIRS, in terms of instrumentation and methodologies that might impact and broaden its use in the hospital.

Hyperspectral imaging (HSI) technologies have been used extensively in medical research, targeting various biological phenomena and multiple tissue types. Their high spectral resolution over a wide range of wavelengths enables acquisition of spatial information corresponding to different light-interacting biological compounds. This review focuses on the application of HSI to monitor brain tissue metabolism and hemodynamics in life sciences. Different approaches involving HSI have been investigated to assess and quantify cerebral activity, mainly focusing on: (1) mapping tissue oxygen delivery through measurement of changes in oxygenated (HbO2) and deoxygenated (HHb) hemoglobin; and (2) the assessment of the cerebral metabolic rate of oxygen (CMRO2) to estimate oxygen consumption by brain tissue. Finally, we introduce future perspectives of HSI of brain metabolism, including its potential use for imaging optical signals from molecules directly involved in cellular energy production. HSI solutions can provide remarkable insight in understanding cerebral tissue metabolism and oxygenation, aiding investigation on brain tissue physiological processes.

Diffuse optics (DO) encompasses a range of photonics tools based on the study of random photon migration in highly scattering media—biological tissues in particular. Due to its unique features, DO is emerging as a powerful means for clinical or homecare diagnostics.¹ The basic physics of DO is related to the detection of temporal or spatial alteration in photon distribution re-emitted on the tissue surface.² Due to the low power (typically few mW) of injected near-infrared light (600- to 1100-nm range), DO is inherently noninvasive. The photon temporal (or spatial) distribution carries information on the absorption—ultimately related to tissue chemical composition, such as water, lipid, collagen content, oxy- and deoxy-hemoglobin concentration, cytochrome c-oxidase³—and scattering properties—linked to tissue microstructure. Further, DO is one of the few noninvasive modalities capable of providing functional information, e.g., brain or muscle activation.⁴ It can be operated noncontact through remote light illumination and collection.⁵ It explores the tissue well below the skin at depths of up to 2 to 4 cm. It can provide quantitative operator-independent assessment of the tissue status, such as hemoglobin oxygenation level in the brain. Finally, it is highly scalable, sharing the same technology from large clinical tomographic systems down to wearable devices or homecare appliances.⁶ For all these aspects, DO is attracting more and more interest in many fields, such as monitoring vital signs like brain oxygenation in critical care or during interventions,⁷ tumor diagnostics as for breast cancer,⁸ investigating the impact of lifestyle and nutrition on our body,⁹ or other fields such as neuroscience and psychology,¹⁰ sports, and leisure.¹¹ Even further, the operator independence, the depth sensitivity, and the scalability in addition to noninvasiveness make this option attractive for telemedicine and homecare of patients remotely.

We present and validate a multi-wavelength time-domain near-infrared spectroscopy (TD-NIRS) system that avoids switching wavelengths and instead exploits the full capability of a supercontinuum light source by emitting and acquiring signals for the whole chosen range of wavelengths. The system was designed for muscle and brain oxygenation monitoring in a clinical environment. A pulsed supercontinuum laser emits broadband light and each of two detection modules acquires the distributions of times of flight of photons (DTOFs) for 16 spectral channels (used width 12.5 nm / channel), providing a total of 32 DTOFs at up to 3 Hz. Two emitting fibers and two detection fiber bundles allow simultaneous measurements at two positions on the tissue or at two source-detector separations. Three established protocols (BIP, MEDPHOT, and nEUROPt) were used to quantitatively assess the system’s performance, including linearity, coupling, accuracy, and depth sensitivity. Measurements were performed on 32 homogeneous phantoms and two inhomogeneous phantoms (solid and liquid). Furthermore, measurements on two blood-lipid phantoms with a varied amount of blood and Intralipid provide the strongest validation for accurate tissue oximetry. The retrieved hemoglobin concentrations and oxygen saturation match well with the reference values that were obtained using a commercially available NIRS system (OxiplexTS) and a blood gas analyzer (ABL90 FLEX), except a discrepancy occurs for the lowest amount of Intralipid. In-vivo measurements on the forearm of three healthy volunteers during arterial (250 mmHg) and venous (60 mmHg) cuff occlusions provide an example of tissue monitoring during the expected hemodynamic changes that follow previously well-described physiologies. All results, including quantitative parameters, can be compared to other systems that report similar tests. Overall, the presented TD-NIRS system has an exemplary performance evaluated with state-of-the-art performance assessment methods.

Tissue oximetry with near-infrared spectroscopy (NIRS) is a technique for the measurement of absolute tissue oxygen saturation (StO₂). Offering a real-time and non-invasive assessment of brain oxygenation and haemodynamics, StO₂ has potential to be used for the assessment of newborn brain injury. Multiple algorithms have been developed to measure StO₂, however, issues with low measurement accuracy or extracranial tissue signal contamination remain. In this work, we present a novel algorithm to recover StO₂ in the neonate, broadband multidistance oximetry (BRUNO), based on a measurement of the gradient of attenuation against distance measured with broadband NIRS. The performance of the algorithm was compared to two other published algorithms, broadband fitting (BF) and spatially resolved spectroscopy (SRS). The median error when recovering StO₂ in light transport simulations on a neonatal head mesh was 0.4% with BRUNO, 4.2% with BF and 9.5% with SRS. BRUNO was more sensitive to brain tissue oxygenation changes, shown in layered head model simulations. Comparison of algorithm performance during full oxygenation-deoxygenation cycles in a homogeneous dynamic blood phantom showed significant differences in the dynamic range of the algorithms; BRUNO recovered StO₂ over 0–100%, BF over 0–90% and SRS over 39–80%. Recovering StO₂ from data collected in a neonate treated at the neonatal intensive care showed different baseline values; mean StO₂ was 64.9% with BRUNO, 67.2% with BF and 73.2% with SRS. These findings highlight the effect of StO₂ algorithm selection on oxygenation recovery; applying BRUNO in the clinical care setting could reveal further insight into complex haemodynamic processes occurring during neonatal brain injury.

We present a novel hyperspectral imaging (HSI) system using visible and near-infrared (NIR) light on the exposed cerebral cortex of animals, to monitor and quantify in vivo changes in the oxygenation of haemoglobin and in cellular metabolism via measurement of the redox states of cytochrome-c-oxidase (CCO). The system, named hNIR, is based on spectral scanning illumination at 11 bands (600, 630, 665, 784, 800, 818, 835, 851, 868, 881 and 894 nm), using a supercontinuum laser coupled with a rotating Pellin-Broca prism. Image reconstruction is performed with the aid of a Monte Carlo framework for photon pathlength estimation and post-processing correction of partial volume effects. The system is validated on liquid optical phantoms mimicking brain tissue haemodynamics and metabolism, and finally applied in vivo on the exposed cortex of mice undergoing alternating oxygenation challenges. The results of the study demonstrate the capacity of hNIR to map and quantify the haemodynamic and metabolic states of the exposed cortex at microvascular levels. This represents (to the best of our knowledge) the first example of simultaneous mapping and quantification of cerebral haemoglobin and CCO in vivo using visible and NIR HSI, which can potentially become a powerful tool for better understanding brain physiology.