Pattern of hemodynamic impairment in multiple sclerosis: Dynamic susceptibility contrast perfusion MR imaging at 3.0 T

Abstract

This study aimed to determine regional pattern of tissue perfusion in the normal-appearing white matter (NAWM) of patients with primary-progressive (PP), relapsing-remitting (RR) multiple sclerosis (MS) and healthy controls, and to investigate the association between perfusion abnormalities and clinical disability. Using dynamic susceptibility contrast (DSC) perfusion MRI at 3 T, we studied 22 patients with clinically definite MS, 11 with PP-MS and 11 with RR-MS and 11 age- and gender-matched healthy volunteers. The MRI protocol included axial dual-echo, dynamic susceptibility contrast enhanced (DSC) T2*-weighted and post-contrast T1-weighted images. Absolute cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the periventricular, frontal, occipital NAWM and in the splenium of the corpus callosum. Compared to controls, CBF and CBV were significantly lower in all NAWM regions in both PP-MS patients (p values from <0.0001 to 0.001) and RR-MS (p values from <0.0001 to 0.020). Compared to RR-MS, PP-MS patients showed significantly lower CBF in the periventricular NAWM (p=0.002) and lower CBV in the periventricular and frontal NAWM (p values: 0.0029 and 0.022). EDSS was significantly correlated with the periventricular CBF (r=-0.48, p=0.0016) and with the periventricular and frontal CBV (r=-0.42, p=0.015; r=-0.35, p=0.038, respectively). This study suggests that the hemodynamic abnormalities of NAWM have clinical relevance in patients with MS. DSC perfusion MRI might provide a relevant objective measure of disease activity and treatment efficacy.

Retinal Vascular Density Using Optical Coherence Tomography-Angiography in Optic Neuritis

“…In the first hypothesis, there is a reduction in metabolic demand resulting from axonal and neuronal loss (RNFL and GCL) [ 10 ], leading to a regression of the vessels of the superficial plexus, which vascularized the axons and bodies of the retinal ganglion cells (RNFL and CGL) [ 19 ]. This hypothesis is consistent with other reports showing a decrease of cerebral perfusion in areas of apparently healthy white substance in MS [ 20 ]. This hypoperfusion would be due to impairment in astrocyte metabolism, in particular poor K+ absorption leading to poor arteriolar dilatation [ 21 ].…”

Retinal Vascular Density Using Optical Coherence Tomography-Angiography in Optic Neuritis

“…In the first hypothesis, there is a reduction in metabolic demand resulting from axonal and neuronal loss (RNFL and GCL) [ 10 ], leading to a regression of the vessels of the superficial plexus, which vascularized the axons and bodies of the retinal ganglion cells (RNFL and CGL) [ 19 ]. This hypothesis is consistent with other reports showing a decrease of cerebral perfusion in areas of apparently healthy white substance in MS [ 20 ]. This hypoperfusion would be due to impairment in astrocyte metabolism, in particular poor K+ absorption leading to poor arteriolar dilatation [ 21 ].…”

White matter and deep gray matter hemodynamic changes in multiple sclerosis patients with clinically isolated syndrome

“…The present data, showing that RRMS patients exhibit significantly lower CBF values in the NAWM and DGM, as compared to controls, are in agreement with previous nuclear medicine (50) and DSC‐MRI investigations (18–22). The globally decreased perfusion in MS is thought to result from diffuse perivascular inflammation, leading to microvessel damage, thrombosis, and fibrin deposition, as proved by histopathologic studies (14).…”

“…There is also no evidence of hemodynamic alterations at the hippocampi of patients with MS with other perfusion techniques. More importantly, the agreement of our findings on patients with RRMS with those of previous studies employing the DSC‐MRI technique (18–21) enhances the validity of our results.…”

Brain grey matter perfusion in primary progressive multiple sclerosis: Mild decrease over years and regional associations with cognition and hand function

“…These findings may indicate that loss of CBFs is rather associated with neurodegeneration than with inflammation in the long run. Our estimated absolute CBF values in the white matter of PPMS subjects are similar to those in the literature [3,17] and the values in the cortex of our controls are consistent with the values found in normal subjects [36]. Unfortunately, data on cortical perfusion in PPMS patients are very scarce and limit the comparison with our results.…”

“…At a global level, we found lower CBFs values were associated with greater disability in all physical tests (T25FW, NHPT) and EDSS, which seems to be in line with the abovementioned mechanisms, and which resembled the brain perfusion dynamic during the disease course. This extends previous research in smaller and usually crosssectional cohorts, which found rather weak [14,17] or no associations [3,9,13,16] with EDSS. In contrast, higher CBFs values indicated worse SDMT performance.…”

Retinal Vascular Density Using Optical Coherence Tomography-Angiography in Optic Neuritis

“…In the first hypothesis, there is a reduction in metabolic demand resulting from axonal and neuronal loss (RNFL and GCL) [ 10 ], leading to a regression of the vessels of the superficial plexus, which vascularized the axons and bodies of the retinal ganglion cells (RNFL and CGL) [ 19 ]. This hypothesis is consistent with other reports showing a decrease of cerebral perfusion in areas of apparently healthy white substance in MS [ 20 ]. This hypoperfusion would be due to impairment in astrocyte metabolism, in particular poor K+ absorption leading to poor arteriolar dilatation [ 21 ].…”

White matter and deep gray matter hemodynamic changes in multiple sclerosis patients with clinically isolated syndrome

“…The present data, showing that RRMS patients exhibit significantly lower CBF values in the NAWM and DGM, as compared to controls, are in agreement with previous nuclear medicine (50) and DSC‐MRI investigations (18–22). The globally decreased perfusion in MS is thought to result from diffuse perivascular inflammation, leading to microvessel damage, thrombosis, and fibrin deposition, as proved by histopathologic studies (14).…”

“…There is also no evidence of hemodynamic alterations at the hippocampi of patients with MS with other perfusion techniques. More importantly, the agreement of our findings on patients with RRMS with those of previous studies employing the DSC‐MRI technique (18–21) enhances the validity of our results.…”

Brain grey matter perfusion in primary progressive multiple sclerosis: Mild decrease over years and regional associations with cognition and hand function

“…These findings may indicate that loss of CBFs is rather associated with neurodegeneration than with inflammation in the long run. Our estimated absolute CBF values in the white matter of PPMS subjects are similar to those in the literature [3,17] and the values in the cortex of our controls are consistent with the values found in normal subjects [36]. Unfortunately, data on cortical perfusion in PPMS patients are very scarce and limit the comparison with our results.…”

“…At a global level, we found lower CBFs values were associated with greater disability in all physical tests (T25FW, NHPT) and EDSS, which seems to be in line with the abovementioned mechanisms, and which resembled the brain perfusion dynamic during the disease course. This extends previous research in smaller and usually crosssectional cohorts, which found rather weak [14,17] or no associations [3,9,13,16] with EDSS. In contrast, higher CBFs values indicated worse SDMT performance.…”

Retinal Vascular Density Using Optical Coherence Tomography-Angiography in Optic Neuritis

“…In the first hypothesis, there is a reduction in metabolic demand resulting from axonal and neuronal loss (RNFL and GCL) [ 10 ], leading to a regression of the vessels of the superficial plexus, which vascularized the axons and bodies of the retinal ganglion cells (RNFL and CGL) [ 19 ]. This hypothesis is consistent with other reports showing a decrease of cerebral perfusion in areas of apparently healthy white substance in MS [ 20 ]. This hypoperfusion would be due to impairment in astrocyte metabolism, in particular poor K+ absorption leading to poor arteriolar dilatation [ 21 ].…”

White matter and deep gray matter hemodynamic changes in multiple sclerosis patients with clinically isolated syndrome

“…The present data, showing that RRMS patients exhibit significantly lower CBF values in the NAWM and DGM, as compared to controls, are in agreement with previous nuclear medicine (50) and DSC‐MRI investigations (18–22). The globally decreased perfusion in MS is thought to result from diffuse perivascular inflammation, leading to microvessel damage, thrombosis, and fibrin deposition, as proved by histopathologic studies (14).…”

“…There is also no evidence of hemodynamic alterations at the hippocampi of patients with MS with other perfusion techniques. More importantly, the agreement of our findings on patients with RRMS with those of previous studies employing the DSC‐MRI technique (18–21) enhances the validity of our results.…”

Brain grey matter perfusion in primary progressive multiple sclerosis: Mild decrease over years and regional associations with cognition and hand function

“…These findings may indicate that loss of CBFs is rather associated with neurodegeneration than with inflammation in the long run. Our estimated absolute CBF values in the white matter of PPMS subjects are similar to those in the literature [3,17] and the values in the cortex of our controls are consistent with the values found in normal subjects [36]. Unfortunately, data on cortical perfusion in PPMS patients are very scarce and limit the comparison with our results.…”

“…At a global level, we found lower CBFs values were associated with greater disability in all physical tests (T25FW, NHPT) and EDSS, which seems to be in line with the abovementioned mechanisms, and which resembled the brain perfusion dynamic during the disease course. This extends previous research in smaller and usually crosssectional cohorts, which found rather weak [14,17] or no associations [3,9,13,16] with EDSS. In contrast, higher CBFs values indicated worse SDMT performance.…”