Stuart Clare

Characterization and propagation of uncertainty in diffusion-weighted MR imaging.

A fully probabilistic framework is presented for estimating local probability density functions on parameters of interest in a model of diffusion. This technique is applied to the estimation of parameters in the diffusion tensor model, and also to a simple partial volume model of diffusion. In both cases the parameters of interest include parameters defining local fiber direction. A technique is then presented for using these density functions to estimate global connectivity (i.e., the probability of the existence of a connection through the data field, between any two distant points), allowing for the quantification of belief in tractography results. This technique is then applied to the estimation of the cortical connectivity of the human thalamus. The resulting connectivity distributions correspond well with predictions from invasive tracer methods in nonhuman primate. Magn Reson Med 50:1077–1088, 2003.

Exacerbation of Pain by Anxiety Is Associated with Activity in a Hippocampal Network

It is common clinical experience that anxiety about pain can exacerbate the pain sensation. Using event-related functional magnetic resonance imaging (FMRI), we compared activation responses to noxious thermal stimulation while perceived pain intensity was manipulated by changes in either physical intensity or induced anxiety. One visual signal, which reliably predicted noxious stimulation of moderate intensity, came to evoke low anxiety about the impending pain. Another visual signal was followed by the same, moderate-intensity stimulation on most of the trials, but occasionally by discriminably stronger noxious stimuli, and came to evoke higher anxiety. We found that the entorhinal cortex of the hippocampal formation responded differentially to identical noxious stimuli, dependent on whether the perceived pain intensity was enhanced by pain-relevant anxiety. During this emotional pain modulation, entorhinal responses predicted activity in closely connected, affective (perigenual cingulate), and intensity coding (mid-insula) areas. Our finding suggests that accurate preparatory information during medical and dental procedures alleviates pain by disengaging the hippocampus. It supports the proposal that during anxiety, the hippocampal formation amplifies aversive events to prime behavioral responses that are adaptive to the worst possible outcome.

Sources of distortion in functional MRI data.

Functional magnetic resonance image (fMRI) experiments rely on the ability to detect subtle signal changes in magnetic resonance image time series. Any areas of signal change that correlate with the neurological stimulus can then be identified and compared with a corresponding high‐resolution anatomical scan. This report reviews some of the several artefacts that are frequently present in fMRI data, degrading their quality and hence their interpretation. In particular, the effects of magnetic field inhomogeneities are described, both on echo planar imaging (EPI) data and on spiral imaging data. The modulation of these distortions as the subject moves in the magnet is described. The effects of gradient coil nonlinearities and EPI ghost correction schemes are also discussed. Hum. Brain Mapping 8:80–85, 1999.

Rapid T(1) mapping using multislice echo planar imaging.

Determination of neurological pathology in white matter disease can be made in a semiquantitative way from T1‐ or T2‐weighted images. A higher level of quantification based on measured T1 or T2 values has been either limited to specific regions of interest or to low‐resolution maps. Higher‐resolution T1 maps have proved difficult to obtain due to the excessively long scan times required using conventional techniques. In this study, clinically acceptable images are obtained by using single‐shot echo planar imaging (EPI) with an acquisition scheme that maximizes signal‐to‐noise while minimizing the scan time. Magn Reson Med 45:630–634, 2001.

White matter and lesion T1 relaxation times increase in parallel and correlate with disability in multiple sclerosis

Previous studies have established the clinical relevance of hypointense lesions (“black holes”) on T1-weighted MRI as a surrogate marker for pathological change [36]. In contrast to measuring the volume of “black holes”, the direct measurement of T1 values allows an objective assessment of the changes contributing to hypointensity both in the focal lesions and in the normal appearing white matter (NAWM). The aims of this study were first, to determine the relationship between T1 values in the NAWM and in discrete lesions, second, to test the relationship between white matter T1 changes and measures of disability and third, to determine whether pathology leading to T1 change occurred in thalamic grey matter of patients with multiple sclerosis. 24 patients with clinically definite multiple sclerosis (13 with relapsing-remitting multiple sclerosis and 11 with secondary progressive multiple sclerosis) and 11 controls participated. White matter T1 histograms and mean T1 values for the thalamus were generated from whole brain T1 relaxation time maps measured using a novel echo-planar imaging based MRI sequence at 3Tesla. Tissue segmentation based on T2- and T1-weighted images allowed independent study of changes in lesions and NAWM. White matter T1 histograms from the patient group showed a reduced peak height and a shift towards higher T1 values (p = 0.028) relative to controls. The mean thalamic T1 was greater for secondary progressive patients than for healthy controls (p = 0.03). Mean white matter T1 values correlated significantly with disability (r = 0.48, p = 0.02). The mean T1 value in the T1-hypointense lesions correlated strongly with the mean T1 value in the NAWM (r = 0.80, p < 0.001). No significant relationship was found between mean white matter T1 value and cerebral volume (r = −0.23, p = 0.31). The T1 measurements extend previous observations suggesting that changes in the NAWM occur in parallel with pathology in lesions of MS. T1 measurements of either the total or NAWM therefore may provide a potentially observer- and scanner- independent marker of pathology relevant to disability in MS.

Independent anatomical and functional measures of the V1/V2 boundary in human visual cortex

The cerebral cortex has both anatomical and functional specialization, but the level of correspondence between the two in the human brain has remained largely elusive. Recent successes in high-resolution magnetic resonance imaging of myeloarchitecture patterns in the cortex suggest that it may now be possible to compare directly human anatomy and function in vivo. We independently investigated the anatomical and functional borders between primary and secondary human visual areas (V1 and V2) in vivo. Functional borders were mapped with functional magnetic resonance imaging (fMRI) using a narrow, vertical black and white contrast-reversing wedge. In three separate scanning sessions, anatomical images were collected at three different slice orientations (300 microm x 300 microm, slice thickness, 1.5 mm). The anatomical signature of V1 was determined by the presence of a hypointense band in the middle of the cortical gray matter. The band was identified in between 81% and 33% (mean 57%) of V1 defined using fMRI, and less than 5% of the identified band was in cortex outside V1. Intensity profiles taken through the gray matter on the V1 and V2 sides of the functional border indicate a measurable difference in the size of the hypointense band for all subjects. This is the first demonstration that the definition of V1 by fMRI closely matches the anatomically defined striate cortex in the human brain. The development of very high-resolution structural MRI may permit the definition of cortical areas based on myeloarchitecture when functional definition is not possible.

Reliable identification of the auditory thalamus using multi-modal structural analyses.

The medial geniculate body (MGB) of the thalamus is a key component of the auditory system. It is involved in relaying and transforming auditory information to the cortex and in top-down modulation of processing in the midbrain, brainstem, and ear. Functional imaging investigations of this region in humans, however, have been limited by the difficulty of distinguishing MGB from other thalamic nuclei. Here, we introduce two methods for reliably delineating MGB anatomically in individuals based on conventional and diffusion MRI data. The first uses high-resolution proton density weighted scanning optimized for subcortical grey-white contrast. The second uses diffusion-weighted imaging and probabilistic tractography to automatically segment the medial and lateral geniculate nuclei from surrounding structures based on their distinctive patterns of connectivity to the rest of the brain. Both methods produce highly replicable results that are consistent with published atlases. Importantly, both methods rely on commonly available imaging sequences and standard hardware, a significant advantage over previously described approaches. In addition to providing useful approaches for identifying the MGB and LGN in vivo, our study offers further validation of diffusion tractography for the parcellation of grey matter regions on the basis of their connectivity patterns.

FSL: New tools for functional and structural brain image analysis

FSL: New Tools for Functional and Structural Brain Image Analysis Stephen Smith*, Peter R Bannister *, Christian Beckmann*, Mike Brady?, Stuart Glare*, David Flitney*, Peter Hansen*, Mark Jenkinson*, Didier Leibovici*, Brian Ripley+, Mark Woolrich*, Yongyue Zhang* *FMRIB, Oxford University, UK “FMedical Vision Lab, Dept. Engineering Science, Oxford University, UK

Noninvasive Quantification of 2-Hydroxyglutarate in Human Gliomas with IDH1 and IDH2 Mutations.

Dept. Statistics, Oxford University, UK

fMRI reveals neural activity overlap between adult and infant pain

Mutations in the isocitrate dehydrogenase genes (IDH1/2) occur often in diffuse gliomas, where they are associated with abnormal accumulation of the oncometabolite 2-hydroxyglutarate (2-HG). Monitoring 2-HG levels could provide prognostic information in this disease, but detection strategies that are noninvasive and sufficiently quantitative have yet to be developed. In this study, we address this need by presenting a proton magnetic resonance spectroscopy ((1)H-MRS) acquisition scheme that uses an ultrahigh magnetic field (≥ 7T) capable of noninvasively detecting 2-HG with quantitative measurements sufficient to differentiate mutant cytosolic IDH1 and mitochondrial IDH2 in human brain tumors. Untargeted metabolomics analysis of in vivo (1)H-MRS spectra discriminated between IDH-mutant tumors and healthy tissue, and separated IDH1 from IDH2 mutations. High-quality spectra enabled the quantification of neurochemical profiles consisting of at least eight metabolites, including 2-HG, glutamate, lactate, and glutathione in both tumor and healthy tissue voxels. Notably, IDH2 mutation produced more 2-HG than IDH1 mutation, consistent with previous findings in cell culture. By offering enhanced sensitivity and specificity, this scheme can quantitatively detect 2-HG and associated metabolites that may accumulate during tumor progression, with implications to better monitor patient responses to therapy.