Cerebral Arterial Bolus Arrival Time is Prolonged in Multiple Sclerosis and Associated with Disability

Abstract

Alterations in the overall cerebral hemodynamics have been reported in multiple sclerosis (MS); however, their cause and significance is unknown. While potential venous causes have been examined, arterial causes have not. In this study, a multiple delay time arterial spin labeling magnetic resonance imaging sequence at 3T was used to quantify the arterial hemodynamic parameter bolus arrival time (BAT) and cerebral blood flow (CBF) in normal-appearing white matter (NAWM) and deep gray matter in 33 controls and 35 patients with relapsing-remitting MS. Bolus arrival time was prolonged in MS in NAWM (1.0 ± 0.2 versus 0.9±0.2 seconds, P ¼ 0.031) and deep gray matter (0.90±0.18 versus 0.80±0.14 seconds, P ¼ 0.001) and CBF was increased in NAWM (14 ± 4 versus 10 ± 2 mL/100 g/min, P ¼ 0.001). Prolonged BAT in NAWM (P ¼ 0.042) and deep gray matter (P ¼ 0.01) were associated with higher expanded disability status score. This study demonstrates alteration in cerebral arterial hemodynamics in MS. One possible cause may be widespread inflammation. Bolus arrival time was longer in patients with greater disability independent of atrophy and T 2 lesion load, suggesting alterations in cerebral arterial hemodynamics may be a marker of clinically relevant pathology.

Impaired retinal microcirculation in multiple sclerosis

“…However, this is unlikely because none of the eyes had a history of optic neuritis, and the relationship between the retinal blood flow metrics and RNFL thickness was not established. Our findings are compatible with slower blood flow in the cerebral arteries of patients with MS measured by Arterial Spin Labeling Magnetic Resonance Imaging 26 and prolongation of the mean transit time, a measure of the average time contrast takes to transit from the arterial to venous circulation in normal appearing white matter, as described in the dynamic susceptibility contrast MRI study. 6 The retinal hypoperfusion is in alignment with the observation of cerebral hypoperfusion in NAWGM in MS. 27,28 The cerebral hypoperfusion is considered a major step that induces a status defined as energy failure in MS. 29 According to a recent large scale clinical study on 1249 patients, MS lesions tend to occur in areas with lower perfusion.…”

Brain perfusion by arterial spin labeling MRI in multiple sclerosis

“…Interestingly, a reduction of GM CBF measured by ASL was confirmed in all MS patients compared to healthy controls while NAWM CBF has been alternatively found decreased in some studies [9][10][11], or increased in others [12,13]. The reason for the increased NAWM CBF in few studies could be the incomplete separation between NAWM and both WM and enhanced lesions due to the relatively coarse resolution of ASL and non-use of exogenous contrast.…”

“…Although ASL technique has limitations such as the relatively low spatial resolution and the requirement of a careful position of region of interests to prevent partial volume effects with lesions and blood vessels, it provides a sensitive measure of cerebral perfusion without the need of a contrast since it uses the blood as an endogenous contrast agent [13]. Therefore, ASL might become a useful tool to evaluate experimental neuroprotective drugs in proof-ofconcept studies and reduce both patients' exposure to gadolinium and the costs of clinical trials requesting serial MRIs.…”

Cause and prevention of demyelination in a model multiple sclerosis lesion

“…The most obvious potential cause of hypoxia in MS is inadequate vascular perfusion, which does not necessarily imply a reduction in perfusion from normal levels, but several studies have nonetheless revealed cerebral hypoperfusion in MS (recently reviewed in D'Haeseleer et al,22 Juurlink,23 Paling et al24). …”