Postmortem verification of MS cortical lesion detection with 3D DIR
ABSTRACT To assess the sensitivity and specificity of 3D double inversion recovery (DIR) MRI for detecting multiple sclerosis (MS) cortical lesions (CLs) using a direct postmortem MRI to histopathology comparison.
Single-slab 3D DIR and 3D fluid-attenuated inversion recovery (FLAIR) images of 56 matched fresh brain samples from 14 patients with chronic MS were acquired at 1.5 T. The images of both sequences were prospectively scored for CLs in consensus by 3 experienced raters who were blinded to histopathology and clinical data. Next, CLs were identified histopathologically and were scored again on 3D DIR and 3D FLAIR (retrospective scoring). CLs were classified as intracortical or mixed gray matter (GM)-white matter lesions. Deep GM lesions were also scored. False-positive scores were noted and, from this, specificity was calculated.
We found a sensitivity for 3D DIR to detect MS CLs of 18%, which is 1.6-fold higher than 3D FLAIR (improves to 37% with retrospective scoring; 2.0-fold higher than 3D FLAIR). We detected mixed GM-white matter lesions with a sensitivity of 83% using 3D DIR (65% sensitivity for 3D FLAIR), which improved to 96% upon retrospective scoring (91% for 3D FLAIR). For purely intracortical lesions, 3D DIR detected more than 2-fold more than 3D FLAIR (improved to >3-fold upon retrospective scoring). The specificity of 3D DIR to MS CLs was found to be 90%.
In this postmortem verification study, we have shown that 3D DIR is highly pathologically specific, and more sensitive to CLs than 3D FLAIR in MS.
[Show abstract] [Hide abstract]
ABSTRACT: Background: Over time, exposure to cerebrovascular risk factors and carotid artery disease may cause multiple asymptomatic brain cortical and subcortical microinfarcts, which are commonly found at brain autopsy. So far, lack of convenient neuroimaging tools limited the investigation of grey matter ischemic damage in vivo. We applied the Double Inversion Recovery (DIR) sequence to explore the impact of carotid artery disease on intracortical ischemic lesion load in vivo, taking into account the impact of demographic characteristics and vascular risk factors. Methods: DIR was acquired in 62 patients with common cerebrovascular risk factors stratified in three groups according to carotid artery disease severity. Intracortical lesions scored on DIR (DIRlns) were classified by vascular territory, lobe and hemisphere. White matter hyperintensities (WMHs) volume was also quantified on Fluid Attenuated Inversion Recovery sequence (FLAIR). Results: Among demographic characteristics and cerebrovascular risk variables explored, General Linear Model indicated that age and carotid artery disease were significantly associated to DIRlns. After correcting for age, DIRlns load was found to be significantly dependent on carotid artery stenosis severity (F(2, 58) = 5.56, p = 0.006). A linear positive correlation between DIRlns and WMHs was found after correcting for age (p = 0.003). Conclusions: Carotid disease severity is associated with DIRlns accrual. Microembolism and impaired cerebral hemodynamics may act as physiopathological mechanisms underlying cortical ischemic damage. The role of other factors, such as small vessel disease and the possible interaction with carotid disease, remains to be further explored. © 2014 S. Karger AG, Basel.Cerebrovascular Diseases 12/2014; 39(1):23-30. DOI:10.1159/000369292 · 3.70 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Background: Neocortical lesions (NLs) are an important pathological component of multiple sclerosis (MS), but their visualization by magnetic resonance imaging (MRI) remains challenging. Objectives: We aimed at assessing the sensitivity of multi echo gradient echo (ME-GRE) T-2*-weighted MRI at 7.0 Tesla in depicting NLs compared to myelin and iron staining. Methods: Samples from two MS patients were imaged post mortem using a whole body 7T MRI scanner with a 24-channel receive-only array. Isotropic 200 micron resolution images with varying T-2* weighting were reconstructed from the ME-GRE data and converted into R-2* maps. Immunohistochemical staining for myelin (proteolipid protein, PLP) and diaminobenzidine-enhanced Turnbull blue staining for iron were performed. Results: Prospective and retrospective sensitivities of MRI for the detection of NLs were 48% and 67% respectively. We observed MRI maps detecting only a small portion of 20 subpial NLs extending over large cortical areas on PLP stainings. No MRI signal changes suggestive of iron accumulation in NLs were observed. Conversely, R-2* maps indicated iron loss in NLs, which was confirmed by histological quantification. Conclusions: High-resolution post mortem imaging using R-2* and magnitude maps permits detection of focal NLs. However, disclosing extensive subpial demyelination with MRI remains challenging.PLoS ONE 10/2014; 9(10):e108863. DOI:10.1371/journal.pone.0108863 · 3.53 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: We summarize MRI measures currently available to assess treatment efficacy and safety in multiple sclerosis (MS) clinical trials and discuss novel metrics that could enter the clinical arena in the near future. In relapsing remitting MS, MRI measures of disease activity (new T2 and gadolinium-enhancing lesions) provide a good surrogacy of treatment effect on relapse rate and disability progression; however, their value in progressive MS remains elusive. For the progressive disease forms, these measures need to be combined with quantities assessing the extent of irreversible tissue loss, which have already been introduced in some clinical trials (e.g., evolution of active lesions into permanent black holes and brain atrophy). Novel measures (e.g., quantification of gray matter and spinal cord atrophy) have demonstrated a great value in explaining patients' clinical outcome, but still need to be fully validated. Despite showing promise, evaluations of cortical lesions, of microscopic tissue abnormalities, and of functional cortical reorganization are still some way off for monitoring of treatment effects. Trial outcomes in MS should include measures of inflammation and neurodegeneration, which should be combined according to the disease clinical phenotype, phase of the study, and the supposed mechanism of action of the drug tested.Current opinion in neurology 06/2014; 27(3):290-9. DOI:10.1097/WCO.0000000000000095 · 5.73 Impact Factor