Preprint Reduced Oxygen Extraction Fraction in Deep Cerebral Veins Associated with Cognitive Impairment in Multiple Sclerosis, 2024, Sawan et al.

[SNT Gatchaman]

Reduced Oxygen Extraction Fraction in Deep Cerebral Veins Associated with Cognitive Impairment in Multiple Sclerosis
Hasan Sawan; Chenyang Li; Sagar Buch; Evanthia Bernitsas; Ewart Mark Haacke; Yulin Ge; Yongsheng Chen

Studying the relationship between cerebral oxygen utilization and cognitive impairment is essential to understanding neuronal functional changes in the disease progression of multiple sclerosis (MS). This study explores the potential of using venous susceptibility in internal cerebral veins (ICVs) as an imaging biomarker for cognitive impairment in relapsing-remitting MS (RRMS) patients.

Quantitative susceptibility mapping derived from fully flow-compensated MRI phase data was employed to directly measure venous blood oxygen saturation levels (SvO2) in the ICVs.

Results revealed a significant reduction in the susceptibility of ICVs (212.4 ± 30.8 ppb vs 239.4 ± 25.9 ppb) and a significant increase of SvO2 (74.5 ± 1.89 % vs 72.4 ± 2.23 %) in patients with RRMS compared with age-and sex-matched healthy controls. Both the susceptibility of ICVs (r = 0.646, p = 0.004) and the SvO2 (r = -0.603, p = 0.008) exhibited a strong correlation with cognitive decline in these patients assessed by the Paced Auditory Serial Addition Test, while no significant correlation was observed with clinical disability measured by the Expanded Disability Status Scale.

The findings suggest that venous susceptibility in ICVs has the potential to serve as a specific indicator of oxygen metabolism and cognitive function in RRMS.


Link | PDF (Preprint: MedRxiv)

 

[SNT Gatchaman]

Several hypotheses underlie progressive neurodegeneration in MS. One explanation revolves around energy deficiency in lesions, termed virtual (also known as metabolic or histotoxic) hypoxia. In contrast to “true” hypoxia, virtual hypoxia does not necessarily involve reduced oxygen availability; rather, it is characterized by diminished oxygen utilization with mitochondrial dysfunction. Virtual hypoxia likely plays a significant role in the pathophysiology of neurodegeneration in MS. This effect is not just localized to lesions; reduced oxygen extraction fraction (OEF), a marker of cell degeneration or dysfunction, has been described in normal-appearing tissue, including in deep and cortical gray matter of MS patients.

Deep cerebral veins such as internal cerebral veins (ICVs) drain the periventricular white matter (WM) where most MS lesions including the slowly expanding lesions occur, as well as subcortical grey matter nuclei which are associated with cognitive function.

The observed increased SvO2 in the ICVs is likely due to reduced oxygen consumption in the deep cerebral regions that drain into the ICV, which include periventricular WM and deep gray matter regions. The superior thalamostriate veins, which drain the corpus striatum and thalamus, unite with the superior choroid veins, which drain the hippocampus, fornix, and corpus callosum, to become the ICVs.

WM damage is also of note, as the subependymal veins, which drain the periventricular WM regions through medullary veins, in turn drain into the ICVs.

In summary, this study demonstrates the feasibility of using deep cerebral venous susceptibility as an imaging biomarker of cognitive impairment in MS. This pilot study warrants further investigation of cerebral venous QSM as a clinically feasible tool in assessing cerebral oxygen metabolism in large-scale prospective clinical studies in MS and other neurodegenerative disorders.

 

[SNT Gatchaman]

Published as —

Reduced oxygen extraction fraction in deep cerebral veins associated with cognitive impairment in multiple sclerosis (2024)
Hasan Sawan; Chenyang Li; Sagar Buch; Evanthia Bernitsas; E Mark Haacke; Yulin Ge; Yongsheng Chen

Studying the relationship between cerebral oxygen utilization and cognitive impairment is essential to understanding neuronal functional changes in the disease progression of multiple sclerosis (MS).

This study explores the potential of using venous susceptibility in internal cerebral veins (ICVs) as an imaging biomarker for cognitive impairment in relapsing-remitting MS (RRMS) patients. Quantitative susceptibility mapping derived from fully flow-compensated MRI phase data was employed to directly measure venous blood oxygen saturation levels (SvO2) in the ICVs.

Results revealed a significant reduction in the susceptibility of ICVs (212.4 ± 30.8 ppb vs 239.4 ± 25.9 ppb) and a significant increase of SvO2 (74.5 ± 1.89% vs 72.4 ± 2.23%) in patients with RRMS compared with age- and sex-matched healthy controls. Both the susceptibility of ICVs (r = 0.508, p = 0.031) and the SvO2 (r = -0.498, p = 0.036) exhibited a moderate correlation with cognitive decline in these patients assessed by the Paced Auditory Serial Addition Test, while no significant correlation was observed with clinical disability measured by the Expanded Disability Status Scale.

The findings suggest that venous susceptibility in ICVs has the potential to serve as a specific indicator of oxygen metabolism and cognitive function in RRMS.

Link | PDF (Journal of Cerebral Blood Flow & Metabolism)