Rasha Abdel-Fahim

Central Veins in Brain Lesions Visualized With High-Field Magnetic Resonance Imaging: A Pathologically Specific Diagnostic Biomarker for Inflammatory Demyelination in the Brain

IMPORTANCE There is no single test that is diagnostic for multiple sclerosis (MS), and existing diagnostic criteria are imperfect. This can lead to diagnostic delay. Some patients require multiple (sometimes invasive) investigations, and extensive clinical follow-up to confirm or exclude a diagnosis of MS. A diagnostic biomarker that is pathologically specific for the inflammatory demyelination in MS could overhaul current diagnostic algorithms. OBJECTIVE To prospectively assess the diagnostic value of visualizing central veins in brain lesions with magnetic resonance imaging (MRI) for patients with possible MS for whom the diagnosis is uncertain. DESIGN Prospective longitudinal cohort study. The reference standard is a clinical diagnosis that is arrived at (after a mean follow-up of 26 months) by the treating neurologist with a specialist interest in MS. The 7-T MRI scans were analyzed at baseline, by physicians blinded to the clinical data, for the presence of visible central veins. SETTING Academic MS referral center. PARTICIPANTS A consecutive sample of 29 patients referred with possible MS who had brain lesions detected on clinical MRI scans but whose condition remained undiagnosed despite expert clinical and radiological assessments. EXPOSURE Seven-Tesla MRI using a T2*-weighted sequence. MAIN OUTCOMES AND MEASURES The proportion of patients whose condition was correctly diagnosed as MS or as not MS, using 7-T MRI at study onset, compared with the eventual diagnosis reached by treating physicians blinded to the result of the MRI scan. RESULTS Of the 29 patients enrolled and scanned using 7-T MRI, so far 22 have received a clinical diagnosis. All 13 patients whose condition was eventually diagnosed as MS had central veins visible in the majority of brain lesions at baseline. All 9 patients whose condition was eventually not diagnosed as MS had central veins visible in a minority of lesions. CONCLUSIONS AND RELEVANCE In our study, T2*-weighted 7-T MRI had 100% positive and negative predictive value for the diagnosis of MS. Clinical application of this technique could improve existing diagnostic algorithms.

Imaging central veins in brain lesions with 3-T T2*-weighted magnetic resonance imaging differentiates multiple sclerosis from microangiopathic brain lesions

Background: White matter lesions are frequently detected using brain magnetic resonance imaging (MRI) performed for various indications. Most are microangiopathic, but demyelination, including multiple sclerosis (MS), is an important cause; conventional MRI cannot always distinguish between these pathologies. The proportion of lesions with a central vein on 7-T T2*-weighted MRI prospectively distinguishes demyelination from microangiopathic lesions. Objective: To test whether 3-T T2*-weighted MRI can differentiate MS from microangiopathic brain lesions. Methods: A total of 40 patients were studied. Initially, a test cohort of 10 patients with MS and 10 patients with microangiopathic white matter lesions underwent 3-T T2*-weighted brain MRI. Anonymised scans were analysed blind to clinical data, and simple diagnostic rules were devised. These rules were applied to a validation cohort of 20 patients (13 with MS and 7 with microangiopathic lesions) by a blinded observer. Results: Within the test cohort, all patients with MS had central veins visible in >45% of brain lesions, while the rest had central veins visible in <45% of lesions. By applying diagnostic rules to the validation cohort, all remaining patients were correctly categorised. Conclusion: 3-T T2*-weighted brain MRI distinguishes perivenous MS lesions from microangiopathic lesions. Clinical application of this technique could supplement existing diagnostic algorithms.

Cortical lesion load correlates with diffuse injury of multiple sclerosis normal appearing white matter.

Background: Degeneration of central nervous system normal appearing white matter (NAWM) underlies disability and progression in multiple sclerosis (MS). Axon loss typifies NAWM degeneration. Objective: The objective of this paper is to assess correlation between cortical lesion load and magnetisation transfer ratio (MTR) of the NAWM in MS. This was in order to test the hypothesis that cortical lesions cause NAWM degeneration. Methods: Nineteen patients with MS underwent 7 Tesla magnetisation-prepared-rapid-acquisition-gradient-echo (MPRAGE), and magnetisation transfer ratio (MTR) brain magnetic resonance imaging (MRI). Cortical lesions were identified using MPRAGE and MTR images of cortical ribbons. White matter lesions (WMLs) were segmented using MPRAGE images. WML maps were subtracted from white matter volumes to produce NAWM masks. Pearson correlation was calculated for NAWM MTR vs cortical lesion load, and WML volumes. Results: Cortical lesion volumes and counts all had significant correlation with NAWM mean MTR. The strongest correlation was with cortical lesion volumes obtained using MTR images (r = −0.6874, p = 0.0006). WML volume had no significant correlation with NAWM mean MTR (r = −0.08706, p = 0.3615). Conclusion: Our findings are consistent with the hypothesis that cortical lesions cause NAWM degeneration. This implicates cortical lesions in the pathogenesis of NAWM axon loss, which underpins long-term disability and progression in MS.

Subjective discomfort in children receiving 3 T MRI and experienced adults’ perspective on children’s tolerability of 7 T: a cross-sectional questionnaire survey

Objectives To explore the possible discomfort perceived by children participating in 7 T MRI research, and the age range in which children are most likely to tolerate it well. Design A cross-sectional survey using age-appropriate questionnaires containing six measures of subjective discomfort (general discomfort, dizziness, noisiness, claustrophobia and feeling of cold or warm). Setting For children, 3 T clinical scanner in a tertiary referral teaching hospital; for adults, 3 and 7 T scanner in a university research building. Participants Non-sedated children and young people under 18 years of age who underwent 3 T clinical MRI for brain or musculoskeletal scans and adult volunteers attending 7 T with or without 3 T for brain scans. Results 83% (89/107) of involved individuals returned questionnaires. The most common discomfort among 31 children receiving 3 T MRI was noisiness (39%), followed by cold (19%), general discomfort (16%), dizziness (13%) and claustrophobia (10%). The noise was reported more frequently in children younger than 12 years than those older (p=0.021). The most common discomfort for 58 adults receiving 7 T MRI was noisiness (43%). In adults, there was a higher frequency of general discomfort during 7 than 3 T scans (p=0.031). More than 85% of adult respondents thought children aged 12–17 years would tolerate 7 T scans well, but only 35% and 15% thought children aged 10–11 and 8–9 years, respectively, would. Conclusions Noisiness was the most common discomfort across all ages in 3 and 7 T scanners. Although general discomfort was more common during 7 than 3 T scans in adults, most adults thought children aged 12 years or more would tolerate 7 T MRI well. Cautious enrolment of children in 7 T MRI study is warranted, but until there is more evidence of how well those aged 12 years or more tolerate 7 T MRI, we would caution against enrolling younger children.

Imaging gray matter with concomitant null point imaging from the phase sensitive inversion recovery sequence

To present an improved three‐dimensional (3D) interleaved phase sensitive inversion recovery (PSIR) sequence including a concomitantly acquired new contrast, null point imaging (NPI), to help detect and classify abnormalities in cortical gray matter.