A multimodal neuroimaging study of cerebrovascular regulation: protocols and insights of combining electroencephalography, functional near-infrared spectroscopy, transcranial Doppler ultrasound, and physiological parameters.

. The current paper describes the creation of a simultaneous trimodal neuroimaging protocol. The authors detail their methodological design for a subsequent large-scale study, demonstrate the ability to obtain the expected physiologically induced responses across cerebrovascular domains, and describe the pitfalls experienced when developing this approach.

A Hypoxia-Inflammation Cycle and Multiple Sclerosis: Mechanisms and Therapeutic Implications.

Purpose Of Review: Multiple sclerosis (MS) is a complex neurodegenerative disease characterized by inflammation, demyelination, and neurodegeneration. Significant hypoxia exists in brain of people with MS (pwMS), likely contributing to inflammatory, neurodegenerative, and vascular impairments. In this review, we explore the concept of a negative feedback loop between hypoxia and inflammation, discussing its potential role in disease progression based on evidence of hypoxia, and its implications for therapeutic targets.

Quantifying neurovascular coupling through a concurrent assessment of arterial, capillary, and neuronal activation in humans: A multimodal EEG-fNIRS-TCD investigation.

Background: This study explored a novel multimodal neuroimaging approach to assess neurovascular coupling (NVC) in humans using electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS), and transcranial Doppler ultrasound (TCD).

Methods: Fifteen participants (nine females; age 19-32) completed concurrent EEG-fNIRS-TCD imaging during motor (finger tapping) and visual ("Where's Waldo?") tasks, with synchronized monitoring of blood pressure, capnography, and heart rate. fNIRS assessed microvascular oxygenation within the frontal, motor, parietal, and occipital cortices, while the middle and posterior cerebral arteries (MCA/PCA) were insonated using TCD.

Maximizing the Reliability and Precision of Measures of Prefrontal Cortical Oxygenation Using Frequency-Domain Near-Infrared Spectroscopy.

Frequency-domain near-infrared spectroscopy (FD-NIRS) has been used for non-invasive assessment of cortical oxygenation since the late 1990s. However, there is limited research demonstrating clinical validity and general reproducibility. To address this limitation, recording duration for adequate validity and within- and between-day reproducibility of prefrontal cortical oxygenation was evaluated.

Heart Rate Variability and Pulse Rate Variability: Do Anatomical Location and Sampling Rate Matter?

Wearable technology and neuroimaging equipment using photoplethysmography (PPG) have become increasingly popularized in recent years. Several investigations deriving pulse rate variability (PRV) from PPG have demonstrated that a slight bias exists compared to concurrent heart rate variability (HRV) estimates. PPG devices commonly sample at ~20-100 Hz, where the minimum sampling frequency to derive valid PRV metrics is unknown.

Adolescent Sport-Related Concussion and the Associated Neurophysiological Changes: A Systematic Review.

Background: Sport-related concussion (SRC) has been shown to induce cerebral neurophysiological deficits, quantifiable with electroencephalography (EEG). As the adolescent brain is undergoing rapid neurodevelopment, it is fundamental to understand both the short- and long-term ramifications SRC may have on neuronal functioning. The current systematic review sought to amalgamate the literature regarding both acute/subacute (≤28 days) and chronic (>28 days) effects of SRC in adolescents via EEG and the diagnostic accuracy of this tool.

The Effect of Hypercapnia on Cortical Metabolic Rate and Mitochondrial Redox Status.

Hypercapnia is commonly used as a vasodilatory stimulus in both basic and clinical research. There have been conflicting reports about whether cerebral metabolic rate of oxygen (CMRO) is maintained at normal levels during increases of cerebral blood flow (CBF) and oxygen delivery caused by hypercapnia.This study aims to provide insight into how hypercapnia may impact CMRO and brain mitochondrial function.

Temporal Pattern of Cortical Hypoxia in Multiple Sclerosis and Its Significance on Neuropsychological and Clinical Measures of Disability.

Objective: Multiple sclerosis (MS) is a degenerative disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. It has been hypothesized that hypoxia plays a role in the pathogenesis of MS. This study was undertaken to investigate the reproducibility of non-invasively measured cortical microvascular hemoglobin oxygenation (S O ) using frequency domain near-infrared spectroscopy (fdNIRS), investigate its temporal pattern of hypoxia in people with MS (pwMS), and its relationship with neurocognitive function and mood.

Impact of averaging fNIRS regional coherence data when monitoring people with long term post-concussion symptoms.

Significance: Functional near-infrared spectroscopy (fNIRS), with its measure of delta hemoglobin concentration, has shown promise as a monitoring tool for the functional assessment of neurological disorders and brain injury. Analysis of fNIRS data often involves averaging data from several channel pairs in a region. Although this greatly reduces the processing time, it is uncertain how it affects the ability to detect changes post injury.

The temporal neurovascular coupling response remains intact during sinusoidal hypotensive and hypertensive challenges.

. Neurovascular coupling (NVC) describes the coupling of neuronal metabolic demand to blood supply, which has shown to be impaired with chronic hypertension, as well as with prolonged hypotension. However, it is unknown the extent the NVC response remains intact during transient hypo- and hyper-tensive challenges.

Enhanced liver X receptor signalling reduces brain injury and promotes tissue regeneration following experimental intracerebral haemorrhage: roles of microglia/macrophages.

Background: Inflammation-exacerbated secondary brain injury and limited tissue regeneration are barriers to favourable prognosis after intracerebral haemorrhage (ICH). As a regulator of inflammation and lipid metabolism, Liver X receptor (LXR) has the potential to alter microglia/macrophage (M/M) phenotype, and assist tissue repair by promoting cholesterol efflux and recycling from phagocytes. To support potential clinical translation, the benefits of enhanced LXR signalling are examined in experimental ICH.

The relationship between cytochrome c oxidase, CBF and CMRO in mouse cortex: A NIRS-MRI study.

Quantifying relationships between cerebral blood flow (CBF), mitochondrial function (cytochrome c oxidase oxidation state), and metabolic rate of oxygen (CMRO) could provide useful insight into normal neurovascular coupling, as well as regulation of oxidative metabolism in neurological disorders. This paper uses a multimodal NIRS-MRI method to quantify these parameters in rodent brain and, in so doing, provides novel information on the regulation of oxygen metabolism by stimulating with hypercapnia or variations in oxygenation. Under hypercapnia, although oxygenation, oxidation state, and CBF increased, there was no increase in CMRO.

Cerebral Hemodynamics and Microvasculature Changes in Relation to White Matter Microstructure After Pediatric Mild Traumatic Brain Injury: An A-CAP Pilot Study.

Advanced neuroimaging techniques show promise as a biomarker for mild traumatic brain injury (mTBI). However, little research has evaluated cerebral hemodynamics or its relation to white matter microstructure post-mTBI in children. This novel pilot study examined differences in cerebral hemodynamics, as measured using functional near-infrared spectroscopy (fNIRS), and its association with diffusion tensor imaging (DTI) metrics in children with mTBI or mild orthopedic injury (OI) to address these gaps.

NIRS Studies Show Reduced Interhemispheric Functional Connectivity in Individuals with Multiple Sclerosis That Exhibit Cortical Hypoxia.

Many with multiple sclerosis (MS) have low cortical microvascular oxygen levels (hypoxia), which have been previously proposed to exacerbate inflammation in MS. We do not know if hypoxia impacts or relates to brain function. We hypothesise that within the MS population, those who have hypoxia may show reduced brain functional connectivity (FC).

Detecting monocyte trafficking in an animal model of glioblastoma using R* and quantitative susceptibility mapping.

Background: The role of tumor-associated macrophages (TAMs) in glioblastoma (GBM) disease progression has received increasing attention. Recent advances have shown that TAMs can be re-programmed to exert a pro-inflammatory, anti-tumor effect to control GBMs. However, imaging methods capable of differentiating tumor progression from immunotherapy treatment effects have been lacking, making timely assessment of treatment response difficult.

Utilization of focused ultrasound for opening of the blood-nerve barrier.

. Focused ultrasound (FUS) use with and without microbubbles (MB) for investigation of the blood-nerve barrier (BNB) within the peripheral nervous system (PNS) has been performed in this study. We evaluate the feasibility of BNB opening in a rodent sciatic nerve model by direct vision FUS treatment and provide preliminary results of magnetic resonance guided FUS (MRgFUS).

The effects of prenatal bisphenol A exposure on brain volume of children and young mice.

Bisphenol A (BPA) is a synthetic chemical used for the manufacturing of plastics, epoxy resin, and many personal care products. This ubiquitous endocrine disruptor is detectable in the urine of over 80% of North Americans. Although adverse neurodevelopmental outcomes have been observed in children with high gestational exposure to BPA, the effects of prenatal BPA on brain structure remain unclear.

Treatment of Persistent Postconcussion Syndrome With Repetitive Transcranial Magnetic Stimulation Using Functional Near-Infrared Spectroscopy as a Biomarker of Response: Protocol for a Randomized Controlled Clinical Trial.

Background: Approximately one-third of all concussions lead to persistent postconcussion syndrome (PPCS). Repetitive transcranial magnetic stimulation (rTMS) is a form of noninvasive brain stimulation that has been extensively used to treat refractory major depressive disorder and has a strong potential to be used as a treatment for patients with PPCS. Functional near-infrared spectroscopy (fNIRS) has already been used as a tool to assess patients with PPCS and may provide insight into the pathophysiology of rTMS treatment in patients with PPCS.

Neurovascular coupling on trial: How the number of trials completed impacts the accuracy and precision of temporally derived neurovascular coupling estimates.

Standard practices for quantifying neurovascular coupling (NVC) with transcranial Doppler ultrasound (TCD) require participants to complete one-to-ten repetitive trials. However, limited empirical evidence exists regarding how the number of trials completed influences the validity and reliability of temporally derived NVC metrics. Secondary analyses was performed on 60 young healthy participants (30 females/30 males) who completed eight cyclical eyes-closed (20-seconds), eyes-open (40-seconds) NVC trials, using the visual paradigm.

Abnormal oxidative metabolism in the cuprizone mouse model of demyelination: An in vivo NIRS-MRI study.

Disruptions in oxidative metabolism may occur in multiple sclerosis and other demyelinating neurological diseases. The impact of demyelination on metabolic rate is also not understood. It is possible that mitochondrial damage may be associated with many such neurological disorders.

Quantification of cytochrome c oxidase and tissue oxygenation using CW-NIRS in a mouse cerebral cortex.

We provide a protocol for measuring the absolute concentration of the oxidized and reduced state of cytochrome c oxidase (CCO) in the cerebral cortex of mice, using broadband continuous-wave NIRS. The algorithm (NIR-AQUA) allows for absolute quantification of CCO and deoxyhemoglobin. Combined with an anoxia pulse, this also allows for quantification of total hemoglobin, and tissue oxygen saturation.

PD-1 independent of PD-L1 ligation promotes glioblastoma growth through the NFκB pathway.

Brain tumor–initiating cells (BTICs) drive glioblastoma growth through not fully understood mechanisms. Here, we found that about 8% of cells within the human glioblastoma microenvironment coexpress programmed cell death 1 (PD-1) and BTIC marker. Gain- or loss-of-function studies revealed that tumor-intrinsic PD-1 promoted proliferation and self-renewal of BTICs.