Reduced cortical microvascular oxygenation in multiple sclerosis: a blinded, case-controlled study using a novel quantitative near-infrared spectroscopy method

Abstract

Hypoxia (low oxygen) is associated with many brain disorders as well as inflammation, but the lack of widely available technology has limited our ability to study hypoxia in human brain. Multiple sclerosis (MS) is a poorly understood neurological disease with a significant inflammatory component which may cause hypoxia. We hypothesized that if hypoxia were to occur, there should be reduced microvascular hemoglobin saturation (StO2). In this study, we aimed to determine if reduced StO2 can be detected in MS using frequency domain near-infrared spectroscopy (fdNIRS). We measured fdNIRS data in cortex and assessed disability of 3 clinical isolated syndrome (CIS), 72 MS patients and 12 controls. Control StO2 was 63.5 ± 3% (mean ± SD). In MS patients, 42% of StO2 values were more than 2 × SD lower than the control mean. There was a significant relationship between StO2 and clinical disability. A reduced microvascular StO2 is supportive (although not conclusive) that there may be hypoxic regions in MS brain. This is the first study showing how quantitative NIRS can be used to detect reduced StO2 in patients with MS, opening the door to understanding how microvascular oxygenation impacts neurological conditions.

Near‐Infrared Spectroscopy Reveals Brain Hypoxia and Cerebrovascular Dysregulation in Primary Biliary Cholangitis

“…We have identified a striking reduction in cortical tissue StO 2 levels in the frontal cortex of some patients with PBC at rest (Fig. ), similar in magnitude to levels previously reported by us in the frontal cortices of patients suffering with the neuroinflammatory disease MS . In the setting of increased platelet–immune–CEC interactions and altered vessel dynamics discussed above, we propose that hypoxia results from a physical reduction in blood flow through the brain microvasculature, coupled with a local increase in metabolic activity (due to heightened local immune cell activity).…”

“…Tight regulation of cerebral blood flow is critical to ensure normal brain oxygenation and function. Cerebrovascular dysfunction and hypoxia have been implicated in a range of neurodegenerative and neuroinflammatory disorders including Alzheimer's disease and multiple sclerosis (MS) . We have shown, using functional MRI, that patients with PBC exhibit alterations in functional hyperemia, although it remains difficult to determine whether alterations in functional hyperemia arise solely from altered brain activity or whether cerebrovascular dysfunction plays a role …”

“…Cerebrovascular dysfunction and hypoxia have been implicated in a range of neurodegenerative and neuroinflammatory disorders including Alzheimer's disease and multiple sclerosis (MS). (5,6) We have shown, using functional MRI, that patients with PBC exhibit alterations in functional hyperemia, (7) although it remains difficult to determine whether alterations in functional hyperemia arise solely from altered brain activity or whether cerebrovascular dysfunction plays a role. (8) Near-infrared spectroscopy (NIRS) allows for noninvasive measurement of oxygenated (O 2 Hb) and deoxygenated hemoglobin (HHb) concentrations in cortical brain tissue.…”

Gray Matter Hypoxia in the Brain of the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis

“…Using quantitative near-infrared spectroscopy, it has been reported that approximately half of MS patients have reduced oxygen saturation in cortical GM [24]. Reduced oxygen saturation is likely to correlate with reduced tissue PO 2 .…”

“…Quantitative near-infrared spectroscopy data indicates that as many as half of MS patients may have hypoxia in the cortex [24]. In EAE mice, MRI measurements sensitive to deoxyhemoglobin provided evidence for hypoxia in the spinal cord [25].…”