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Interindividual variation in neurovascular reserve and its relationship with cognitive performance is not well understood in imaging in neurodegeneration. We assessed the neurovascular reserve in amnestic mild cognitive impairment (aMCI) and Alzheimer's dementia (AD). Twenty-eight healthy controls (HC), 15 aMCI, and 20 AD patients underwent blood oxygen level-dependent imaging for 9 minutes, breathing alternatively air and 7% carbon dioxide mixture. The data were parcellated into 88 anatomic regions, and carbon dioxide regressors accounting for different washin and washout velocities were fitted to regional average blood oxygen level-dependent signals. Velocity of cerebrovascular reactivity (CVR) was analyzed and correlated with cognitive scores. aMCI and AD patients had significantly slower response than HC (mean time to reach 90% of peak: HC 33 seconds, aMCI and AD 59 seconds). CVR velocity correlated with Mini Mental State Examination in 35 of 88 brain regions (p = 0.019, corrected for multiple comparisons), including 10 regions of the default-mode network, an effect modulated by age. This easily applicable protocol yielded a practical assessment of CVR in cognitive decline., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Several controlled studies provide evidence that treatment with interferon beta in patients with a first event suggestive of multiple sclerosis (MS) delays conversion to clinically definite MS (CDMS). Our aim was to determine whether early initiation of treatment with interferon beta prevents development of confirmed disability in MS., Methods: In the initial placebo-controlled phase of the double-blinded BENEFIT study, patients with a first event suggestive of MS and a minimum of two clinically silent lesions in MRI were randomised to receive either interferon beta-1b 250 microg (n=292) or placebo (n=176) subcutaneously every other day for 2 years, or until diagnosis of CDMS. Patients were then eligible to enter the follow-up phase with open-label interferon beta-1b. In the current prospectively planned analysis 3 years after randomisation, the effects of early interferon beta-1b treatment were compared with those of delayed treatment initiated after diagnosis of CDMS or after 2 years on the study. The primary outcomes of this ITT analysis were time to diagnosis of CDMS, time to confirmed expanded disability status scale (EDSS) progression, and score on a patient-reported functional assessment scale (FAMS-TOI). This trial is registered with ClinicalTrials.gov, number NCT00185211., Findings: Of the 468 patients originally randomised, 418 (89%) entered the follow-up phase; 392 (84%) completed 3 years' post-randomisation follow-up. After 3 years, 99 (37%) patients in the early group developed CDMS compared with 85 (51%) patients in the delayed treatment group. Early treatment reduced the risk of CDMS by 41% (hazard ratio 0.59, 95% CI 0.44-0.80; p=0.0011; absolute risk reduction 14%) compared with delayed treatment. Over 3 years, 42 (16%) patients in the early group and 40 (24%) in the delayed group had confirmed EDSS progression; early treatment reduced the risk for progression of disability by 40% compared with delayed treatment (0.60, 0.39-0.92; p=0.022; absolute risk reduction 8%). The FAMS-TOI score was high and stable in both groups over the 3-year period (p=0.31)., Interpretation: Our data suggest that early initiation of treatment with interferon beta-1b prevents the development of confirmed disability, supporting its use after the first manifestation of relapsing-remitting MS.

Background: Individuals with an At Risk Mental State (ARMS) have a very high risk of developing a psychotic disorder but the basis of this risk is unclear. We addressed this issue by studying gray matter volume in this group with magnetic resonance imaging (MRI)., Methods: Thirty-five individuals with an ARMS, 25 patients with first episode schizophrenia, and 22 healthy volunteers were studied using a 1.5T MRI scanner. Twelve (34%) of the ARMS group developed schizophrenia in the 2 years subsequent to scanning., Results: There were significant volumetric differences between the three groups in the left insula, superior temporal gyrus, cingulate gyrus and precuneus. In these regions, the volume in the ARMS group was smaller than in volunteers but not significantly different from that in the first episode (FE) group. Direct comparison of the ARMS and control groups revealed additional areas of reduced volume in the left medial temporal cortex. Within the ARMS group, those subjects who later developed psychosis had less gray matter than subjects who did not in the right insula, inferior frontal and superior temporal gyrus., Conclusions: The ARMS was associated with reductions in gray matter volume in areas that are also reduced in schizophrenia, suggesting that these are a correlate of an increased vulnerability to psychosis. Volumetric differences within the ARMS group may be related to the subsequent onset of schizophrenia in a subset of those at high risk.

The aim of our study was to determine whether T2-weighted (T2w) MRI of the brain could be performed immediately after the administration of gadopentetate dimeglumine (gadolinium DTPA) in patients with multiple sclerosis (MS) without a loss in image quality or diagnostic reliability. Sixteen patients with clinically diagnosed MS were included in the study. Twenty-four patients with various cerebral pathologies (14 patients with multiple lacunar lesions) were examined in order to exclude masking of T2 hyperintense lesions other than MS lesions. Images of 10 patients without pathological changes served as a control condition for the qualitative analysis. In these 50 patients, T1w and T2w MRI was performed before and after the administration of gadolinium DTPA. Signal intensities were measured within T2 hyperintense cerebral lesions, in T1-enhancing lesions and in normal appearing brain tissue on T2w turbo spin-echo (TSE) sequences. Both quantitative and qualitative analysis did not show significant differences between T2w pre- and postcontrast series. T2w MRI performed prior to and after the administration of gadolinium DTPA provides similar information in patients with MS. With a TR of 3.2 s, not a single lesion was obscured on T2w postcontrast series. Acquisition of T2w MR images immediately after the administration of gadolinium DTPA allows for shorter examination time and assures sufficient time for contrast enhancement in cerebral lesions with a disrupted blood-brain barrier.

Regional cerebral blood volume (rCBV) provides valuable information about the nature and progress of diseases of the central nervous system. While relative rCBV maps can be derived directly from dynamic susceptibility contrast data, the arterial input function (AIF) has to be measured for absolute rCBV quantification. For determination of the AIF pixels located completely within a feeding artery must be selected. However, by using a region-of-interest (ROI) based selection some confounding effects can occur, especially if single shot echo planar imaging (EPI) with low spatial resolution is used. In this study we analyzed the influence of partial volume effects and spatial misregistration due to frequency shifts induced by paramagnetic contrast agents. We analyzed AIFs from the internal carotid artery (ICA), the vertebral artery (VA) and the middle cerebral artery (MCA) using gamma variate function based parameterization. The concentration time curves (CTC) of several pixels which were selected on the basis of strong signal drop appeared distorted during the bolus passage. Moreover, the amplitudes of input functions derived from the MCA were smaller by a factor of three as compared to those of the ICA and VA. Simulations revealed that these effects can be attributed to a spatial shift of the vessel along phase-encoding direction during the passage of the bolus. We therefore developed a procedure for a pixel selection based on cluster analysis which classifies pixels according to the parameters of the fitted gamma variate functions. This approach accounted for misregistration of the vessel and yielded very consistent results for a group of normal subjects.

Cerebral gliomas may cause a reduction of glucose metabolism in the cerebellum contralateral to the tumor side (crossed cerebellar diaschisis, CCD). We investigated whether CCD is related to tumor localization, histological grade, size and tumor biochemistry. Cerebellar glucose metabolism was measured in 44 glioma patients and 15 healthy subjects using positron emission tomography and [18F]fluorodeoxyglucose (FDG). CCD was determined by calculating an asymmetry index of cerebellar glucose metabolism. Further, the tumor uptake of FDG and [11C]methionine (MET) was also assessed, and was expressed as ratio of normalized tracer uptake in tumor over contralateral cortex (T/C). Frontal lobe tumors were associated with highest CCD values. For these tumors, CCD was higher in malignant (-11.8+/-9.9%) than in low-grade (-4.3+/-4.1%) gliomas (P=0.010). In addition, frontal lobe tumors showed increasing CCD values with increasing size. In tumors of the parietal or temporal lobe, CCD was less marked or absent. T/C ratios of tumor tracer uptake were higher in malignant than in low-grade gliomas, but were not correlated with CCD. Our data indicate that the magnitude of CCD is mainly determined by tumor localization and size, the latter being associated with tumor grade. These findings raise the question whether CCD provides a measure of expansion or progression particularly in low-grade tumors of the frontal lobe.

The influence of the blood-brain barrier (BBB) on tracer uptake was investigated in 21 patients with gliomas and meningiomas using PET, [18F]fluorodeoxyglucose (FDG), [18C]methionine (MET) and the K+ analog rubidium-82 (RUB) whose uptake into brain is largely prevented if the BBB is intact. Tracer uptake was quantitated by (1) multiple time graphical plotting providing tracer distribution volume (VD), unidirectional tracer uptake (Ki), and (2) normalized uptake (NU) which is a measure of net tissue radioactivity related to administered activity and body weight. VD, Ki and NU of MET were higher in meningiomas compared to gliomas and were significantly correlated with NU RUB (Spearman rank: p < 0.005 (VD), p < 0.05 (Ki), p < 0.001 (NU)). NU MET correlated with VD (p < 0.001) and Ki (p < 0.005) of MET. For FDG, tumor VD was in the range of contralateral cortex. Ki and NU values of FDG were highest in glioblastomas. NU of FDG correlated significantly with Ki of FDG (p < 0.005) but not with VD. The results suggest, that alteration of MET uptake in tumors is governed by changes of tracer influx across the BBB, whereas FDG uptake is related to tracer metabolism. This makes FDG the appropriate tracer particularly for the differential diagnosis of contrast enhancing lesions in operated and irradiated patients.