The diagnosis of Creutzfeldt-Jakob disease can still only be made reliably by post-mortem (pm) pathology, and the development of methods to improve early in vivo diagnosis is an important research priority. Magnetic resonance (MR) imaging is very widely used in the non-invasive investigation of neurological diseases but so far only preliminary data are available about its potential in the diagnosis of CJD. Abnormalities of in vivo MR signal intensity have been observed in the deep grey matter. Furthermore, in unpublished work within the partnership, extensive signal change has also been observed in pm MR scans and this appears to correspond well with pathological changes. If these early observations are confirmed, it is likely that MR will have an important role to play in the early diagnosis of CJD, by providing non-invasively information about the distribution and severity of pathology in the brain.

QAMRIC is an ambitious project which involves application of state-of-the-art computer processing techniques to in vivo and pm MR and to histopathology data, with careful clinical documentation and thorough validation. Existing datasets will be evaluated and initial quantitative processing carried out on better quality data. Of particular importance are datasets in which in vivo MR, pm MR, and pm histology have been obtained on the same patient. The initial database will be extended in the project with improved techniques for MR and histological data acquisition.

Computer-assisted quantification of intensity and morphological abnormalities in in vivo and pm MR will be carried out using newly-available software. Quantification of histological abnormalities on 2-D sections will mainly use existing tools but new techniques for aligning serial sections to form a 3-D dataset will be developed. Advanced computer matching techniques will be used for co-registration of the of the in vivo and pm MR data and 3-D histology data obtained in the same patient. This will allow detailed analysis of the distribution of changes in the brain and clarification of the pathological changes underlying the in vivo MR signal abnormalities. Co-registration of MR data from different subjects will also be carried out, and will allow improved statistical comparison within- and between- groups of patients and controls, to establish more clearly the sensitivity and specificity of MR for in vivo diagnosis.

Specifications for in vivo MR acquisition will be developed and refined during the project. The protocols will take account of the necessary compromise between, on the one hand, a practical and reliable protocol for clinical use in confused patients, and, on the other, the need to obtain good quality data for demonstration of characteristic abnormalities to assist diagnosis.

Keywords: Creutzfeldt-Jakob disease, magnetic resonance imaging, early diagnosis, quantitative analysis, histopathology, post-mortem MR, registration