Related Experiment Video
Updated: May 22, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Decreased frontal lobe gray matter perfusion in cognitively impaired patients with secondary-progressive multiple
R I Aviv1, P L Francis, R Tenenbein
1Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. richard.aviv@sunnybrook.ca
Background And Purpose:
There is increasing evidence implicating microvascular impairment in MS pathogenesis. Perfusion imaging offers a unique opportunity to investigate the functional impact of GM pathology. We sought to quantify differences in MR imaging-based bookend-derived cerebral perfusion between cognitively impaired and nonimpaired patients with SPMS.
Materials And Methods:
Patients were prospectively recruited and assessed using MR imaging and the standard cognitive battery called the Minimal Assessment of Cognitive Function in MS. Patients exhibiting impairment on ≥ 2 individual tests were classified as cognitively impaired. Healthy controls were prospectively recruited and assessed using MR imaging to validate bookend assumptions. Structural and perfusion scans were coregistered and partitioned into anatomic brain regions and tissue compartments. Clinical and radiologic characteristics were compared between patients with and without impairment to identify potential confounders. A Bonferroni adjusted P value threshold (P < .005) was used for lobar and sublobar level analyses to correct for multiple comparisons.
Results:
Thirty-seven patients with SPMS (age 56 ± 9 years; 23 women, 14 men) and 10 age- and sex-matched healthy controls were recruited. Bookend assumptions were found to be valid in MS. GM and WM qCBV were all globally reduced in impaired patients. After adjusting for potential confounders while examining sublobar level perfusion, only GM qCBV was significantly different between cognitive groups, and this hypoperfusion localized to the bilateral medial superior frontal regions and left inferior, middle, and superior frontal regions (P < .005) of impaired patients compared with nonimpaired patients. GM qCBV accounted for 22.5% of the model variance compared with a model including only confounders (P = .0007).
Conclusions:
Bookend-derived GM qCBV was significantly reduced in cognitively impaired patients with SPMS in functionally relevant brain regions.
Insights
Cognitively impaired patients with secondary progressive multiple sclerosis (SPMS) show reduced gray matter cerebral blood volume (GM qCBV) in specific frontal brain regions. This finding highlights the role of microvascular changes in MS-related cognitive decline.
Area of Science:
- Neuroimaging
- Neurology
- Vascular Biology
Background:
- Microvascular impairment is increasingly implicated in multiple sclerosis (MS) pathogenesis.
- Perfusion imaging offers a method to assess the functional impact of gray matter (GM) pathology in MS.
Purpose of the Study:
- To quantify differences in MR imaging-based bookend-derived cerebral perfusion between cognitively impaired and nonimpaired patients with secondary progressive multiple sclerosis (SPMS).
Main Methods:
- Patients with SPMS and healthy controls underwent MR imaging and cognitive assessments (Minimal Assessment of Cognitive Function in MS).
- Structural and perfusion scans were analyzed to partition brain regions and tissue compartments.
- Statistical analyses, including Bonferroni correction, were used to compare perfusion between cognitive groups and identify confounders.
Main Results:
- Thirty-seven SPMS patients and 10 healthy controls were included.
- Gray matter (GM) and white matter (WM) quantitative cerebral blood volume (qCBV) were globally reduced in impaired patients.
- GM qCBV was significantly reduced in specific frontal regions of cognitively impaired SPMS patients compared to nonimpaired patients, even after adjusting for confounders.
Conclusions:
- Bookend-derived GM qCBV is significantly reduced in cognitively impaired SPMS patients.
- Hypoperfusion in specific frontal GM regions is associated with cognitive impairment in SPMS.
