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Significance: A shortcoming for the routine clinical use of diffuse optics (DO) in the injured head has been that the results from commercial near-infrared spectroscopy-based devices are not reproducible, often give phys iologically invalid values and differ between systems. Besides the limitations due to the physics of continuous23 wave light sources, one culprit is the head heterogeneity and the underlying morphological and functional abnor malities of the probed tissue. Aim: To investigate the effect that different tissue alterations in the damaged head has on DO signals and provide guidelines to avoid data misinterpretation. Approach: DO measurements and computed tomography scans were acquired on brain-injured patients. The relationship between the signals and the underlying tissue types was classified on a case-by-case basis. Results: Examples and suggestions to establish quality control routines were provided. The findings suggested guidelines for carrying out DO measurements and speculations towards improved devices. Conclusions: This study advocates for the standardization of the DO measurements to secure a role for DO in neurocritical care. We suggest that blind measurements are unacceptably problematic due to confounding effects and care using a priori and a posteriori quality control routines that go beyond an assessment of the signal-to-noise ratio that is typically utilized., Preprint

Hyperventilation (HV) therapy uses vasoconstriction to reduce intracranial pressure (ICP) by reducing cerebral blood volume. However, as HV also lowers cerebral blood flow (CBF), it may provoke misery perfusion (MP) where the decrease in CBF is coupled with increased oxygen extraction fraction (OEF). MP may rapidly lead to the exhaustion of brain energy metabolites, making it vulnerable to ischemia. MP is difficult to detect at the bedside, which is where transcranial hybrid, near-infrared spectroscopies are promising since they noninvasively measure OEF and CBF., Peer Reviewed, Postprint (author's final draft)

(English) In the intensive care, the multimodal monitoring of the patient is crucial. The systemic physiology is routinely and comprehensively monitored but the practical monitoring of the brain is lacking. Hybrid diffuse optics (DO) has a potential to fill this gap by combining diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS). DO measures local, microvascular cerebral perfusion/blood flow, oxygen extraction fraction and cerebral metabolic rate of oxygen. Therefore, the overarching purpose of this work was to boost the use of hybrid DO by validating its utility in clinical applications on the human brain, especially in critically ill populations. To achieve this goal, new hybrid DO devices were constructed to enhance the data-rate and the quantification of the intracerebral signals while synchronously acquiring data from clinical monitors. In particular, a new platform combining time-resolved NIRS (TRS) and fast (~40 Hz) DCS was constructed. These were used in the fruitful collaborations with the Vall d'Hebron hospital on different patient cohorts. In a population of patients undergoing surgeries the relationship with electrophysiological assessment of cerebral metabolism, the proprietary bispectral index, and the optically-derived parameters were investigated during propofol-induced anesthesia. This has shown that DO estimates of the oxygen metabolism correlate with this index. The additional DO information could be investigated to evaluate if it can help prevent brain damage due to anesthesia. A cohort of children diagnosed with benign external hydrocephalus undergoing invasive intracranial pressure (ICP) monitoring were monitored during night sleep. This allowed the quantification of the cerebral hemodynamics and metabolism during ICP waves that are indicative of future morbidity in them. This has revealed that ICP waves are associated with hemodynamic and metabolic oscillations. Furthermore, these results have shown that the presence, Postprint (published version)

In this paper, we propose the application of time-domain near-infrared spectroscopy to the assessment of oscillations in cerebral hemodynamics. These oscillations were observed in the statistical moments of the distributions of time of flight of photons (DTOFs) measured on the head. We analyzed the zeroth and second centralized moments of DTOFs (total number of photons and variance) to obtain their spectra to provide parameters for the frequency components of microcirculation, which differ between the extracerebral and intracerebral layers of the head. Analysis of these moments revealed statistically significant differences between a control group of healthy subjects and a group of patients with severe neurovascular disorders, which is a promising result for the assessment of cerebral microcirculation and cerebral autoregulation mechanisms.

An optical technique based on diffuse reflectance measurement combined with indocyanine green (ICG) bolus tracking is extensively tested as a method for the clinical assessment of brain perfusion at the bedside. We report on multiwavelength time-resolved diffuse reflectance spectroscopy measurements carried out on the head of a healthy adult during the intravenous administration of a bolus of ICG. Intracerebral and extracerebral changes in absorption were estimated from an analysis of changes in statistical moments (total number of photons, mean time of flight and variance) of the distributions of times of flight (DTOF) of photons recorded simultaneously at 16 wavelengths from the range of 650-850 nm using sensitivity factors estimated by diffusion approximation based on a layered model of the studied medium. We validated the proposed method in a series of phantom experiments and in-vivo measurements. The results obtained show that changes in the concentration of the ICG can be assessed as a function of time of the experiment and depth in the tissue. Thus, the separation of changes in ICG concentration appearing in intra-and extracerebral tissues can be estimated from optical data acquired at a single source-detector pair of fibers/fiber bundles positioned on the surface of the head.

Transcranial direct current stimulation (tDCS) is currently being used for research and treatment of some neurological and neuropsychiatric disorders, as well as for improvement of cognitive functions. In order to better understand cerebral response to the stimulation and to redefine protocols and dosage, its effects must be monitored. To this end, we have used functional diffuse correlation spectroscopy (fDCS) and time-resolved functional near-infrared spectroscopy (TR-fNIRS) together with electroencephalography (EEG) during and after stimulation of the frontal cortex. Twenty subjects participated in two sessions of stimulation with two different polarity montages and twelve also underwent a sham session. Cerebral blood flow and oxyhemoglobin concentration increased during and after active stimulation in the region under the stimulation electrode while deoxyhemoglobin concentration decreased. The EEG spectrum displayed statistically significant power changes across different stimulation sessions in delta (2 to 4 Hz), theta (4 to 8 Hz), and beta (12 to 18 Hz) bands. Results suggest that fDCS and TR-fNIRS can be employed as neuromonitors of the effects of transcranial electrical stimulation and can be used together with EEG., Peer Reviewed, Postprint (published version)

We present an overview of the wide range of potential applications of optical methods for monitoring traumatic brain injury. The MEDLINE database was electronically searched with the following search terms: traumatic brain injury, head injury, or head trauma, and optical methods, NIRS, near-infrared spectroscopy, cerebral oxygenation, or cerebral oximetry. Original reports concerning human subjects published from January 1980 to June 2015 in English were analyzed. Fifty-four studies met our inclusion criteria. Optical methods have been tested for detection of intracranial lesions, monitoring brain oxygenation, assessment of brain perfusion, and evaluation of cerebral autoregulation or intracellular metabolic processes in the brain. Some studies have also examined the applicability of optical methods during the recovery phase of traumatic brain injury . The limitations of currently available optical methods and promising directions of future development are described in this review. Considering the outstanding technical challenges, the limited number of patients studied, and the mixed results and opinions gathered from other reviews on this subject, we believe that optical methods must remain primarily research tools for the present. More studies are needed to gain confidence in the use of these techniques for neuromonitoring of traumatic brain injury patients.