Iris D. Kilsdonk

Multicontrast MR imaging at 7T in multiple sclerosis: highest lesion detection in cortical gray matter with 3D-FLAIR

BACKGROUND AND PURPOSE: 7T MR imaging has led to improved detection and classification of cortical MS lesions, mainly based on T2*-weighted gradient-echo sequences. Depiction of cortical GM by using the recommended MS imaging protocol has not yet been investigated at 7T. We aimed to investigate prospectively which recommended sequence for clinical use has the highest value at 7T, in terms of GM and WM lesion detection. MATERIALS AND METHODS: Thirty-seven patients with MS (mean age, 43.8 years; 25 women) and 7 healthy controls (mean age, 40.4 years; 5 women) underwent multicontrast 7T MR imaging including the recommended clinical 2D-T2WI, 3D-T1WI, 3D-FLAIR, and GM-specific 3D-DIR. Lesions were scored and categorized anatomically by 3 raters, in consensus. The value of sequences was evaluated lesion-wise and patient-wise (Wilcoxon signed-rank test). RESULTS: At 7T, 3D-FLAIR detected the highest number of total cortical GM lesions (217), 89% more than 3D-DIR and 87% and 224% more than 2D-T2WI and 3D-T1WI. Patient-wise analysis showed that this difference between 3D-FLAIR and 3D-DIR was statistically significant (P < .04), and most pronounced for the number of mixed lesions (P < .03). 3D-FLAIR also detected the highest number of total WM lesions (2605), but the difference with 3D-DIR and 3D-T1WI was not significant. CONCLUSIONS: When using recommended clinical sequences at 7T, the best way to detect cortical GM lesions is with 3D-FLAIR and not by GM-specific 3D-DIR or by conventional 2D-T2WI and 3D-T1WI sequences.

Increased cortical grey matter lesion detection in multiple sclerosis with 7 T MRI: a post-mortem verification study.

The relevance of cortical grey matter pathology in multiple sclerosis has become increasingly recognized over the past decade. Unfortunately, a large part of cortical lesions remain undetected on magnetic resonance imaging using standard field strength. In vivo studies have shown improved detection by using higher magnetic field strengths up to 7 T. So far, a systematic histopathological verification of ultra-high field magnetic resonance imaging pulse sequences has been lacking. The aim of this study was to determine the sensitivity of 7 T versus 3 T magnetic resonance imaging pulse sequences for the detection of cortical multiple sclerosis lesions by directly comparing them to histopathology. We obtained hemispheric coronally cut brain sections of 19 patients with multiple sclerosis and four control subjects after rapid autopsy and formalin fixation, and scanned them using 3 T and 7 T magnetic resonance imaging systems. Pulse sequences included T1-weighted, T2-weighted, fluid attenuated inversion recovery, double inversion recovery and T2*. Cortical lesions (type I-IV) were scored on all sequences by an experienced rater blinded to histopathology and clinical data. Staining was performed with antibodies against proteolipid protein and scored by a second reader blinded to magnetic resonance imaging and clinical data. Subsequently, magnetic resonance imaging images were matched to histopathology and sensitivity of pulse sequences was calculated. Additionally, a second unblinded (retrospective) scoring of magnetic resonance images was performed. Regardless of pulse sequence, 7 T magnetic resonance imaging detected more cortical lesions than 3 T. Fluid attenuated inversion recovery (7 T) detected 225% more cortical lesions than 3 T fluid attenuated inversion recovery (Z = 2.22, P < 0.05) and 7 T T2* detected 200% more cortical lesions than 3 T T2* (Z = 2.05, P < 0.05). Sensitivity of 7 T magnetic resonance imaging was influenced by cortical lesion type: 100% for type I (T2), 11% for type II (FLAIR/T2), 32% for type III (T2*), and 68% for type IV (T2). We conclude that ultra-high field 7 T magnetic resonance imaging more than doubles detection of cortical multiple sclerosis lesions, compared to 3 T magnetic resonance imaging. Unfortunately, (subpial) cortical pathology remains more extensive than 7 T magnetic resonance imaging can reveal.

Determinants of iron accumulation in deep grey matter of multiple sclerosis patients

Background: Iron accumulation in deep grey matter (GM) structures is a consistent finding in multiple sclerosis (MS) patients. This study focused on the identification of independent determinants of iron accumulation using R2* mapping. Subjects and methods: Ninety-seven MS patients and 81 healthy controls were included in this multicentre study. R2* mapping was performed on 3T MRI systems. R2*in deep GM was corrected for age and was related to disease duration, disability, T2 lesion load and brain volume. Results: Compared to controls, R2* was increased in all deep GM regions of MS patients except the globus pallidus and the substantia nigra. R2* increase was most pronounced in the progressive stage of the disease and independently predicted by disease duration and disability. Reduced cortical volume was not associated with iron accumulation in the deep GM with the exception of the substantia nigra and the red nucleus. In lesions, R2* was inversely correlated with disease duration and higher total lesion load. Conclusion: Iron accumulation in deep GM of MS patients is most strongly and independently associated with duration and severity of the disease. Additional associations between cortical GM atrophy and deep GM iron accumulation appear to exist in a region specific manner.

Inflammation High-Field Magnetic Resonance Imaging

Multiple sclerosis (MS) is the most common inflammatory demyelinating disorder of the central nervous system (CNS). MS has been subject to high-field magnetic resonance (MR) imaging research to a great extent during the past years, and much data has been collected that might be helpful in the investigation of other inflammatory CNS disorders. This article reviews the value of high-field MR imaging in examining inflammatory MS abnormalities. Furthermore, possibilities and challenges for the future of high-field MR imaging in MS are discussed.

Perivascular spaces in MS patients at 7 Tesla MRI : A marker of neurodegeneration?

Background: Virchow-Robin spaces (VRS) are associated with vascular and neurodegenerative disease. In multiple sclerosis (MS), VRS have been associated with neuroinflammation. Ultra-high field imaging may be used to gain insight in these contradictory findings. Objective: The objective of this paper is to analyze VRS in MS patients using high-resolution 7 Tesla (T) MRI. Additionally, we investigated whether the widening of VRS is related to inflammatory or neurodegenerative aspects of MS. Methods: Thirty-four MS patients and 11 healthy controls were examined at 7T. Number and size of VRS were measured on three-dimensional (3D) T1-weighted images, and 3D fluid-attenuated inversion recovery (FLAIR) images were used for MS lesion detection. Brain atrophy was quantified by computing supratentorial brain volume fraction (sBVF). VRS counts were correlated with clinical variables, lesion count and sBVF. Results: MS patients displayed more VRS (median 11) than healthy controls (median four), p = 0.001. VRS size did not differ between both groups. VRS count in MS patients was associated with sBVF (rho = −0.40, p = 0.02), but not with lesion count (p = 0.22). Conclusions: The 7T MRI reveals increased numbers of VRS in MS. The finding that VRS are associated with supratentorial brain atrophy, but not with lesion count, suggests that VRS might rather serve as a neurodegenerative than an inflammatory marker in MS.

2010 revisions to mcDonald criteria for diagnosis of multiple sclerosis: Impact of 3-tesla magnetic resonance imaging

with those initially reported by Zamboni (ie, CCSVI in 100% MS and 0% HC), who claimed a causative effect of CCSVI on MS. The second step was to perform in all CCSVI-positive patients blinded selective venography (VGF), considered the unquestionable gold standard by Zamboni himself. VGF was invariably normal: no individual with pMS had evidence of abnormal cerebrospinal venous drainage. Therefore, the comparison should be done between 0 of 50 pMS vs 0 of 50 HC. Curiously, Dr Avruscio, who says he has read our article carefully, has clearly underestimated this important detail of our work. We take this opportunity to underline the importance of designing studies aimed at a more detailed and correct understanding of cerebrospinal venous anatomy and physiology. Indeed, over the last 2 years, we had the possibility—by means of VGF—to observe dramatic pictures of abnormal chronic cerebrospinal venous drainage in individuals with different pathologies, but not affected by MS (Fig). In conclusion, our findings exclude any association between CCSVI and pMS. Moreover, we strongly recommend extreme caution in interpreting an ultrasound-based diagnosis of CCSVI as absolute evidence of a pathological process involving the brain and the spinal cord, which in our opinion requires confirmation by VGF.

Multicenter R2* mapping in the healthy brain.

The R2* relaxation rate constant has been suggested as a sensitive measure for iron accumulation. The aim of this multi‐center study was to assess the inter‐scanner and inter‐subject variability of R2* mapping and to investigate the relationship between brain volume and R2* in specific structures.

Ultra-high field MRI: looking through the ‘macroscope’

The first publications about in vivo application of ultra-high field MRI in multiple sclerosis (MS) appeared in 2008. From then on, the number of studies performed at 7 Tesla (T) has rapidly increased. The main advantage of ultra-high field MRI is its higher signal-to-noise ratio, which can be used to increase spatial resolution greatly. This has led to improved detection of subtle MS pathology, particularly in clinically relevant regions like the grey matter (GM). Another advantage of 7 T MRI is its increased sensitivity to susceptibility effects. This has been used to image additional morphological characteristics of MS lesions.1 For example, susceptibility-weighted MRI at 7 T has confirmed that MS white matter (WM) lesions are consistently …

In-vivo imaging of meningeal inflammation in multiple sclerosis: Presence of evidence or evidence of presence?

Recent histopathology studies suggest the presence of meningeal inflammation in patients with multiple sclerosis (MS) that might be associated with subpial cortical demyelination and a rather worse disease course.1 Although a radiologist is not a pathologist, diagnostic neuroradiology aims to visualize and to detect almost every (subtle) pathological feature of a disease to its full extent. To be able to translate histopathological results into radiological images will create an opportunity to visualize them in an in-vivo setting.

Impact of 3 Tesla MRI on interobserver agreement in clinically isolated syndrome: A MAGNIMS multicentre study

Background: Compared to 1.5 T, 3 T magnetic resonance imaging (MRI) increases signal-to-noise ratio leading to improved image quality. However, its clinical relevance in clinically isolated syndrome suggestive of multiple sclerosis remains uncertain. Objectives: The purpose of this study was to investigate how 3 T MRI affects the agreement between raters on lesion detection and diagnosis. Methods: We selected 30 patients and 10 healthy controls from our ongoing prospective multicentre cohort. All subjects received baseline 1.5 and 3 T brain and spinal cord MRI. Patients also received follow-up brain MRI at 3–6 months. Four experienced neuroradiologists and four less-experienced raters scored the number of lesions per anatomical region and determined dissemination in space and time (McDonald 2010). Results: In controls, the mean number of lesions per rater was 0.16 at 1.5 T and 0.38 at 3 T (p = 0.005). For patients, this was 4.18 and 4.40, respectively (p = 0.657). Inter-rater agreement on involvement per anatomical region and dissemination in space and time was moderate to good for both field strengths. 3 T slightly improved agreement between experienced raters, but slightly decreased agreement between less-experienced raters. Conclusion: Overall, the interobserver agreement was moderate to good. 3 T appears to improve the reading for experienced readers, underlining the benefit of additional training.