Brain perfusion by arterial spin labeling MRI in multiple sclerosis

Abstract

The role of MRI in multiple sclerosis (MS) has been well established for decades. Moreover, new MRI techniques have been developed to better understand the complex pathogenesis of this disease, since the use of conventional MRI techniques is partially limited by its weak associations with clinical features and low sensitivity for gray matter (GM) involvement and diffuse damage of white matter (WM) [1]. These limitations become even more significant in the disease shift from the predominantly inflammatory to degenerative phase [1].MS has been traditionally considered a demyelinating inflammatory disorder of the central nervous system; however, vascular involvement and perfusion abnormalities are recently receiving an increasing interest [2]. Earlier PET and SPECT studies showed metabolic alterations and perfusion deficits in cognitively impaired MS patients, particularly at the cortical level in the left frontal and temporal lobes [3]. Recently, a dynamic susceptibility contrast-enhanced (DSC) MRI showed in MS a globally reduced but regionally mixed cerebral blood flow (CBF). Decreased CBF has been demonstrated in both normalappearing WM (NAWM) [4-7] and deep GM [6,7] in relapsing-remitting MS (RRMS) patients, which had also a significantly reduced CBF in the putamen compared to patients with clinically isolated syndrome (CIS) [7].Interestingly, the greater reduction of NAWM CBF was found in primary-progressive MS compared to RRMS [5, 6], though NAWM CBF was decreased even in CIS patients [7]. A regional increase of CBF has been detected in early lesion stages, up to 3 weeks prior to brain-blood barrier (BBB) breakdown with subsequent contrast enhancement [8]. Furthermore, NAWM CBF was shown to significantly correlate with clinical disability [5], whereas GM CBF correlated with neuropsychological dysfunctions [6].Due to recent increasing availability of higher field strength scanners, a new MRI technique called arterial spin labeling (ASL) has been proposed as a useful research tool in several neurological diseases. 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. Most T1-hypointense lesions were concentrated in WM regions with lower CBF, whilst the T2-hyperintense lesions were distributed in WM regions with both higher and lower CBF [11]. The negative correlations between the T2-hyperintense lesion volume and regional CBF have been showed in several brain areas [14]. Moreover, cerebral vasoreactivity (CVR) from normocapnic to hypercapnic CBF was found diminished in MS patients compared to healthy controls indicating an impaired CBF regulation [15]. Since decreased GM CVR correlated positively with GM atrophy and negatively ...

Early perfusion changes in multiple sclerosis patients as assessed by MRI using arterial spin labeling

“…In recent years, several studies have demonstrated the potential for perfusion MRI in identifying cortical and deep gray matter abnormalities in patients with MS, even in the absence of structural differences (29–32). Almost all studies have used contrast media agents to perform the perfusion sequences.…”

“…Before the contrast gadolinium-enhanced images, we included a prototype sequence to measure perfusion called enhanced ASL. This three-dimensional (3D) stack of spirals sequence (32) has been designed to improve signal-to-noise ratio, reduce artefacts, and acquire multiple post-label delay times that allows us to obtain transit delay time maps, as well as transit time corrected perfusion maps. This sequence was used with the following parameters: TE = 11.5 ms; TR = 5981 ms; post-labeling delay = 1000 ms; perfusion labeling time = 3500 ms; number of delays = 7 (1000 ms, 1220 ms, 1480 ms, 1780 ms, 2150 ms, 2630 ms, and 3320 ms); bandwidth = 62.5 kHz; FA = 155, field of view = 22 cm; spiral acquisition = 640 points × 4 arms; reconstructed image = 128 × 128; and slice thickness = 4.5 mm.…”

“…But perfusion can also be assessed using the perfusion sequence called arterial spin labeling (ASL), without needing contrast agents (22–26), making this sequence suitable for research studies. Only a few reports have already shown a correlation between ASL perfusion changes in gray matter and cognitive and physical disability in MS (27–32).…”

Arterial spin labeling for the measurement of cerebral perfusion and angiography

“…ASL has also found application in epilepsy 181,182 to aid detection of epileptogenic focus by monitoring peri-ictal CBF increases. There is also hope that ASL will have a role in multiple sclerosis, [183][184][185] where correlations have been found between ASL measures and lesion burden and disability. Another emerging use is in head trauma, 186 where ASL has shown specific patterns of perfusion abnormality.…”

Brain Atrophy as a Measure of Neuroprotective Drug Effects in Multiple Sclerosis: Influence of Inflammation

“…It has been suggested that gray matter (GM) volume loss in MS could be a more sensitive indicator of disease progression than white matter (WM) atrophy, as “pseudoatrophy” effects are greater in WM due to its larger inflammatory activity, which is accompanied by blood-brain barrier breakdown, local fluid leakage, and increased brain perfusion (Koudriavtseva et al, 2015 ). These processes are less evident in GM, which is usually characterized by decreased vascular perfusion.…”