The optimization of acquisition parameters for precise measurement of diffusion in anisotropic systems is described. First, an algorithm is presented that minimizes the bias inherent in making measurements with a fixed set of gradient vector directions by spreading out measurements in 3-dimensional gradient vector space. Next, it is shown how the set of b-matrices and echo time can be optimized for estimating the diffusion tensor and its scalar invariants. The standard deviation in the estimate of the tensor trace in a water phantom was reduced by more than 40% and the artefactual anisotropy was reduced by more than 60% when using the optimized scheme compared with a more conventional scheme for the same scan time, and marked improvements are demonstrated in the human brain with the optimized sequences. Use of these optimal schemes results in reduced scan times, increased precision, or improved resolution in diffusion tensor images. Magn Reson Med 42:515-

These findings should help to define a biologically active dose of PTK/ZK. These results suggest that DCE-MRI may be a useful biomarker for defining the pharmacological response and dose of angiogenesis inhibitors, such as PTK/ZK, for further clinical development.

No abstract

A new semi-automatic method for segmenting the spinal cord from MR images is presented. The method is based on an active surface (AS) model of the cord surface, with intrinsic smoothness constraints. The model is initialized by the user marking the approximate cord center-line on a few representative slices, and the compact surface parametrization results in a rapid segmentation, taking on the order of one minute. Using 3-D acquired T 1 -weighted images of the cervical spine from human controls and patients with multiple sclerosis, the intra-and inter-observer reproducibilities were evaluated, and compared favorably with an existing cord segmentation method. While the AS method overestimated the cord area by approximately 14% compared to manual outlining, correlations between cord cross-sectional area and clinical disability scores confirmed the relevance of the new method in measuring cord atrophy in multiple sclerosis. Segmentation of the cord from 2-D multislice T 2 -weighted images is also demonstrated over the cervical and thoracic region. Since the cord center-line is an intrinsic parameter extracted as part of the segmentation process, the image can be resampled such that the center-line forms one coordinate axis of a new image, allowing simple visualization of the cord structure and pathology; this could find wider application in standard radiological practice.

This paper reviews the current applications of diffusion-weighted and diffusion tensor MRI in diseases of the brain white matter. The contribution that diffusion-weighted imaging has made to our understanding of white matter diseases is critically appraised. The quantitative nature of diffusion MRI is one of its major attractions; however, this is offset by the more advanced hardware required to collect diffusion-weighted images reliably, and the more complex processing to produce quantitative parametric diffusion images. With the now common availability of scanners equipped to perform echo-planar imaging, the acquisition of diffusion tensor images is sure to become more widespread and routine.

Many promising MRI approaches for research or clinical management of multiple sclerosis (MS) have recently emerged, or are under development or refinement. Advanced MRI methods need to be assessed to determine whether they allow earlier diagnosis or better identification of phenotypes. Improved post-processing should allow more efficient and complete extraction of information from images. Magnetic resonance spectroscopy should improve in sensitivity and specificity with higher field strengths and should enable the detection of a wider array of metabolites. Diffusion imaging is moving closer to the goal of defining structural connectivity and, thereby, determining the functional significance of lesions at specific locations. Cell-specific imaging now seems feasible with new magnetic resonance contrast agents. The imaging of myelin water fraction brings the hope of Correspondence to: Massimo Filippi, Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, via Olgettina 60, 20132, Milan, Italy filippi.massimo@hsr.it. Contributors RB and MF coordinated the Review. RB prepared an initial draft of the introduction, the new uses of conventional MRI data (lesionbased measures) section, the ultra-high field MRI section, and the conclusions. AJT prepared an initial draft of the diagnosis/classification and optic-nerve imaging sections. MAR prepared, with MF, an initial draft of the magnetisation transfer, functional MRI, and spinalcord imaging sections. DP prepared an initial draft of the proton MR spectroscopy and myelin imaging sections. VD prepared an initial draft of the new contrast agents section. FB prepared an initial draft of the atrophy section. MI prepared an initial draft of the perfusion imaging section. CRGG prepared, with RB, an initial draft of the new uses of conventional MRI data (lesion-based measures) section. MAH prepared, with MF, an initial draft of the diffusion imaging section and drafted the paragraphs on the post-processing methods. MF prepared an initial draft of the magnetisation transfer, diffusion imaging, functional MRI, spinal cord imaging, and conclusions sections. All authors collaborated in all subsequent steps of manuscript preparation.Conflicts of interest RB has received honoraria for lectures and travel expenses, and consulting fees as an investigator in previous and current treatment trials from Biogen Idec, Genentech, Merck-Serono, Teva Neuroscience, and Pepgen. AJT serves on advisory boards for Novartis and Genentech, chairs Teva's data, safety, and monitoring committee for the GA for ALS trial, and has received honoraria for lecturing from Bayer-Schering and Merck-Serono. MAR has received personal compensation for speaking activities from Merck-Serono and BiogenDompè. DP has received personal compensation for speaking activities and consulting services from Biogen Idec, Teva Neuroscience, Synar Inc., and Genentech. VD has received honoraria from Biogen and Guerbet for lectures and travel expenses. FB has received pe...

Serial monthly magnetization transfer (MT) imaging was performed to evaluate whether a change of the normal appearing white matter (NAWM), which precedes the appearance of enhancing lesions, is seen in patients with multiple sclerosis (MS). Every 4 weeks for 3 months, 10 patients with relapsing-remitting MS were scanned with a T1-weighted sequence, 20 minutes after injection with 0.3 mmol/kg gadolinium-DTPA (Gd-DTPA). During each of the monthly sessions, MT and dual echo scans were also performed before Gd-DTPA injection. On coregistered images, the MT ratio (MTR) was measured in NAWM subsequently involved by enhancing lesions, in NAWM areas on the same slices but outside any present or future MR abnormality, and in enhancing lesions at the time of their appearance. Forty-eight new enhancing lesions with no corresponding abnormalities on previous scans were identified. Their average MTR was 33.1% (+/-8.4%). Three, 2, and 1 month before enhancement appearance, the mean MTR in NAWM, measured from areas corresponding to future enhancing lesions, was significantly lower than the mean MTR in NAWM outside enhancing areas; the MTR decreased steadily as the time when the enhanced lesion approached. These results suggest that changes in the NAWM of patients with MS occur before lesions become evident on conventional MRI scans.

Diffusion tensor magnetic resonance imaging (DT-MRI) is unique in providing information about both the structural integrity and the orientation of white matter fibers in vivo and, through "tractography", revealing the trajectories of white matter tracts. DT-MRI is therefore a promising technique for detecting differences in white matter architecture between different subject populations. However, while studies involving analyses of group averages of scalar quantities derived from DT-MRI data have been performed, as yet there have been no similar studies involving the whole tensor. Here we present the first step towards realizing such a study, i.e., the spatial normalization of whole tensor data sets. The approach is illustrated by spatial normalization of 10 DT-MRI data sets to a standard anatomical template. Both qualitative and quantitative approaches are described for assessing the results of spatial normalization. Techniques are then described for combining the spatially normalized data sets according to three definitions of average, i.e., the mean, median, and mode of a distribution of tensors. The current absence of, and hence need for, appropriate statistical tests for comparison of results derived from group-averaged DT-MRI data sets is then discussed. Finally, the feasibility of performing tractography on the group-averaged DT-MRI data set is investigated and the possibility and implications of generating a generic map of brain connectivity from a group of subjects is considered. © 2002 Elsevier Science (USA)