Because of the major difficulties in measuring clinical end points in multiple sclerosis (MS) treatment trials, there has been much enthusiasm for using magnetic resonance imaging (MRI) findings as an alternative outcome. To provide international consensus guidelines for the use of MRI in MS clinical trials, a task force of the US National MS Society was convened. The recommendations of the task force are presented in this review. Given the high sensitivity for detecting pathological activity in relapsing-remitting and secondary progressive MS, monthly T2-weighted and gadolinium-enhanced brain MRI is an excellent tool for short-term exploratory trials of new agents where it serves as the primary end point; in particular, failure to demonstrate a reduction in lesion activity avoids the time, cost, and risks of a larger clinical end point study. However, conventional MRI findings have a limited correlation with disability in established MS. The primary end point of a definitive trial should therefore be clinical, although serial MRI at 6- to 12-month intervals is a useful secondary end point in providing an index of pathological progression. In trials of patients presenting with clinically isolated syndromes suggestive of MS, MRI findings can be used in the entry criteria, and as a secondary outcome measure, but conversion to clinically definite MS should be the primary outcome. The pathological substrates of irreversible disability are demyelination and axonal loss. Putative magnetic resonance markers for these processes include decreased N-acetylaspartate on proton magnetic resonance spectroscopy, decreased magnetization transfer ratios, hypointensity on T1-weighted images, and loss of short T2 water fractions, some of which relate more closely to disability than conventional MRI findings. Further technical developments should lead to more accurate quantitation, greater pathological specificity, and stronger clinical correlations.

This study confirmed the limited correlation between clinical manifestations and T2 burden of disease (BOD) but revealed an important plateauing relationship between T2 BOD and disability.

Standard stereotactic procedures rely upon external cranial landmarks and standardized atlases for localization of subcortical neural regions. Magnetic resonance imaging permits the visualization of the neural structure of the brain in vivo. A stereotactic instrument compatible with a magnetic resonance unit was constructed and together with magnetic resonance imaging a procedure was developed that overcomes the limitations and inaccuracies of the traditional stereotactic methods and allows accurate and reliable localization of subcortical targets in the rhesus monkey brain.

The use of magnetization transfer contrast (MTC) in magnetic resonance imaging of the human knee was evaluated in this study. MTC is generated by irradiating the macromolecular protons in tissue with a low power off-resonance radio-frequency field. This results in a decrease in water proton signal intensity where a tight magnetic coupling between water and macromolecules exists. With this approach, the authors have demonstrated that MTC can improve contrast in standard single-section, gradient-recalled-echo images of the knee with regard to fat-muscle and cartilage-synovial fluid comparisons. The effect of changes in repetition time, echo time, and flip angle were also quantitatively evaluated. More important, MTC was shown to generate useful cartilage-synovial fluid contrast on high-resolution three-dimensional images, in which contrast is difficult to generate. This approach may not only provide better structural information about the knee, but may also provide noninvasive insight into the structure and biochemical composition of cartilage in vivo.