In vivo imaging of cortical pathology in multiple sclerosis using ultra-high field MRI

Abstract

Objective: We used ultra-high field MRI to visualize cortical lesion types described by neuropathology in 16 patients with multiple sclerosis (MS) compared with 8 age-matched controls; to characterize the contrast properties of cortical lesions including T2*, T2, T1, and phase images; and to investigate the relationship between cortical lesion types and clinical data. Methods:We collected, on a 7-T scanner, 2-dimensional fast low-angle shot (FLASH)-T2*-weighted spoiled gradient-echo, T2-weighted turbo spin-echo (TSE) images (0.33 ϫ 033 ϫ 1 mm 3 ), and a 3-dimensional magnetization-prepared rapid gradient echo.Results: Overall, 199 cortical lesions were detected in patients on both FLASH-T2* and T2-TSE scans. Seven-tesla MRI allowed for characterization of cortical plaques into type I (leukocortical), type II (intracortical), and type III/IV (subpial extending partly or completely through the cortical width) lesions as described histopathologically. Types III and IV were the most frequent type of cortical plaques (50.2%), followed by type I (36.2%) and type II (13.6%) lesions. Each lesion type was more frequent in secondary progressive than in relapsing-remitting MS. This difference, however, was significant only for type III/IV lesions. T2*-weighted images showed the highest, while phase images showed the lowest, contrast-to-noise ratio for all cortical lesion types. In patients, the number of type III/IV lesions was associated with greater disability (p Ͻ 0.02 by Spearman test) and older age (p Ͻ 0.04 by Spearman test).Conclusions: Seven-tesla MRI detected different histologic cortical lesion types in our small multiple sclerosis (MS) sample, suggesting, if validated in a larger population, that it may prove a valuable tool to assess the contribution of cortical MS pathology to clinical disability. GLOSSARY ANOVA ϭ analysis of variance; BN ϭ background noise; CNR ϭ contrast-to-noise ratio; DIR ϭ double-inversion recovery; EDSS ϭ Expanded Disability Status Scale; FLAIR ϭ fluid-attenuated inversion recovery; FLASH ϭ fast low-angle shot; GM ϭ gray matter; MPRAGE ϭ magnetization-prepared rapid gradient echo; MR ϭ magnetic resonance; MS ϭ multiple sclerosis; NACGM ϭ normal-appearing cortical gray matter; RF ϭ radiofrequency; ROI ϭ region of interest; RRMS ϭ relapsingremitting multiple sclerosis; SNR ϭ signal-to-noise ratio; SPMS ϭ secondary progressive multiple sclerosis; TA ϭ time of acquisition; TE ϭ echo time; TR ϭ repetition time; TSE ϭ turbo spin-echo; WM ϭ white matter.Although cortical lesions were identified as a common finding in multiple sclerosis (MS) from the earliest pathologic studies, 1-3 their significance was underestimated until recent histopathologic data revealed that they constitute a substantial proportion of the total brain MS lesion load. 4,5 The ability of standard field strength scanners (1.5 T, 3 T) to detect and characterize cortical MS pathology is still significantly lower than neuropathology.6 Ultra-high field systems (7 T to 9.4 T) allow a 2-to 3-fold improvement in image sign...

Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

“…Mild-to-moderate cognitive impairment may not be readily detected even by competent physicians or on EDSS testing, which is insensitive to such changes, [16][17][18] nor can cortical gray matter lesions be easily detected with conventional MRI techniques. 67,68 However, cortical lesions are much more commonly detected pathologically and on MRI with DIR and high-field scans and documented much more easily with neuropsychological testing, even early in the patient's course. 18,74,[84][85][86] Furthermore, in both clinical practice and study trials, neither frequent brain MRI scans nor even infrequent spinal cord MRI scans are regularly obtained, so that many overt MRI lesions in the neuraxis can be missed, and previously hypointense or hyperintense lesions can become isointense and be difficult to detect unless prior MRI studies have been done.…”

“…31 A large and growhigh-field MRI scanners. 67,68 The latter may even allow one to identify remyelination and distinguish perivenous lesions caused by demyelinating diseases from those caused by other neurologic disorders. 69,70 There is also recent evidence that focal MRI white matter lesions in the optic radiations may lead to retrograde gray matter atrophy in the lateral geniculate nucleus.…”

Ultrahochfeld-MRT im Kontext neurologischer Erkrankungen

“…Neben dieser quantitativ verbesserten Detektionsrate ermöglicht die UHF-MRT darüber hinaus eine exaktere in-vivo-Einteilung der KL [70] in ihre vier pathologischen Klassifikationsformen [11], welche in Abbildung 4 dargestellt sind.…”

“…Darauf aufbauend konnte in zwei Studien nachgewiesen werden, dass MS-Patienten mit einer höheren subpialen Läsionslast (Typ III) signifikant höhere Werte auf der Expanded Disability Status Scale (EDSS) aufweisen [18,70]. Weitere sichere Korrelationen mit klinischen Parametern wurden bisher nicht berichtet.…”

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

“…2). For example, MRI performed at high field (≥3T) and specific sequences, such as double inversion recovery imaging, capture larger number of cortical lesions [100,101]. Magnetization transfer imaging, which can be used to quantify intact myelin, has been proposed as a biomarker for remyelination [102].…”