Functional and structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis with a characteristic neuropsychiatric syndrome and severe and prolonged clinical courses. In contrast, standard clinical magnetic resonance imaging (MRI) remains normal in the majority of patients. Here, we investigated structural and functional brain changes in a cohort of patients with anti-NMDAR encephalitis. METHODS: Twenty-four patients with established diagnosis of anti-NMDAR encephalitis and age- and gender-matched controls underwent neuropsychological testing and multimodal MRI, including T1w/T2w structural imaging, analysis of resting state functional connectivity, analysis of white matter using diffusion tensor imaging, and analysis of gray matter using voxel-based morphometry. RESULTS: Patients showed significantly reduced functional connectivity of the left and right hippocampus with the anterior default mode network. Connectivity of both hippocampi predicted memory performance in patients. Diffusion tensor imaging revealed extensive white matter changes, which were most prominent in the cingulum and which correlated with disease severity. In contrast, no differences in T1w/T2w structural imaging and gray matter morphology were observed between patients and controls. INTERPRETATION: Anti-NMDAR encephalitis is associated with characteristic alterations of functional connectivity and widespread changes of white matter integrity despite normal findings in routine clinical MRI. These results may help to explain the clinicoradiological paradox in anti-NMDAR encephalitis and advance the pathophysiological understanding of the disease. Correlation of imaging abnormalities with disease symptoms and severity suggests that these changes play an important role in the symptomatology of anti-NMDAR encephalitis.

Automated vs manual delineations of regions of interest- a comparison in commercially available perfusion MRI software.

BACKGROUND: In perfusion magnetic resonance imaging a manual approach to delineation of regions of interest is, due to rater bias and time intensive operator input, clinically less favorable than an automated approach would be. The goal of our study was to compare the performances of these approaches. METHODS: Using Stroketool, PMA and Perfscape/Neuroscape perfusion maps of cerebral blood flow, mean transit time and Tmax were created for 145 patients with acute ischemic stroke. Volumes of hypoperfused tissue were calculated using both a manual and an automated protocol, and the results compared between methods. RESULTS: The median difference between the automatically and manually derived volumes was up to 210 ml in Perfscape/Neuroscape, 123 ml in PMA and 135 ml in Stroketool. Correlation coefficients between perfusion volumes and radiological and clinical outcome were much lower for the automatic volumes than for the manually derived ones. CONCLUSIONS: The agreement of the two methods was very poor, with the automated use producing falsely exaggerated volumes of hypoperfused tissue. Software improvements are necessary to enable highly automated protocols to credibly assess perfusion deficits.

Fully automated postprocessing carries a risk of substantial overestimation of perfusion deficits in acute stroke magnetic resonance imaging.

BACKGROUND AND PURPOSE: Due to the risk of rater bias and time restrictions in clinical practice, an automated approach to delineation of hypoperfused tissue in patients with acute ischemic stroke would be preferred to a manual one. We tested the hypothesis that existing software solutions, on account of numerous artifacts, produce hypoperfused tissue even in a cohort of patients with no ischemia. METHODS: Thirty-nine patients, all admitted for exclusion of cerebral ischemia or hemorrhage and without a final diagnosis of stroke imaged between September 2008 and May 2009 were included in the study. Using 3 different software packages (PerfScape/NeuroScape, PMA and Stroketool), perfusion maps of mean transit time, cerebral blood flow and T(max) were created for each patient. Three different thresholds were applied to each parameter map, and subsequent volumes of hypoperfused tissue were calculated. RESULTS: The median volume of hypoperfused tissue for all the subjects was 92.9 ml (interquartile range, IQR: 13.3-323.4 ml) when calculated by PerfScape/NeuroScape, 30.42 ml (IQR: 13.9-71.4 ml) when calculated by PMA and 78.71 ml (IQR: 40.3-140.8 ml) when calculated by Stroketool. The volumes derived via the different software applications mostly showed only a weak-to-moderate association with each other (Spearman's correlation coefficient between 0.02 and 0.76). CONCLUSIONS: Although automated protocols show promise, the programs Stroketool, PerfScape and PMA require substantial improvement in order to be able to automatically and reliably differentiate between patients with a credible region of ischemia-related hypoperfusion and those without.

Search for a map and threshold in perfusion MRI to accurately predict tissue fate: a protocol for assessing lesion growth in patients with persistent vessel occlusion.

BACKGROUND: The MRI-based mismatch concept has been used to estimate the risk of infarction in ischemic stroke. Based on multiple studies on magnetic resonance perfusion imaging, it seems unlikely that any perfusion parameter threshold will provide a reliable prediction of radiological or clinical outcome for all patients. The goal of our study was to find a minimally biased yet maximally useful perfusion postprocessing protocol which would offer the treating physician a useful estimate of tissue fate. METHODS: One hundred and forty-five acute ischemic stroke patients, admitted within 24 h after stroke to the Charité-University Medicine Hospital in Berlin between March 2008 and November 2009, were included in this study. Using three different software packages (Perfscape/Neuroscape, PMA and Stroketool), maps of mean transit time, cerebral blood flow (CBF) and T(max) were created. Three different thresholds were applied on each parameter map and subsequent volumes of hypoperfused tissue were calculated. RESULTS: Overall, the maps and thresholds giving the least amount of overestimation of the final infarct volume were T(max) 8 s in Perfscape/Neuroscape, CBF 20 ml/100 g/min in PMA and CBF 15% (of the highest value on the scale for a given patient) in Stroketool. In patients with persistent vessel occlusion, a CBF map with a restrictive threshold showed volumes of tissue at definite risk of infarction in up to 100% of patients. The additional use of a CBF map with a high threshold enabled identification of patients without penumbras. CONCLUSIONS: No combination of software, map and threshold was able to give a reliable estimate of tissue fate for either all patients or any subgroup of patients. However, in patients with vessel occlusion, combination of a CBF map with a low and a high threshold can enable calculation of the minimum volume of brain tissue that will inevitably be lost if the occlusion persists.