The diagnosis of Creutzfeld Jakob disease (CJD) can still only be made reliably by post mortem pathology, and the development of methods to improve early in vivo diagnosis is an important research priority. 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 magnetic resonance (MR) signal intensity have been observed in the deep grey matter, and in a recent series of 29 patients nearly 80% showed distinctive changes. Furthermore, in unpublished preliminary work within the partnership, extensive signal change has also been observed in post mortem MR scans and this appears to correspond well with pathological changes. If these early data are confirmed, it is likely that MR will have an important role to play in the early diagnosis of CJD. It will probably be complementary to promising new biochemical tests and/ or peripheral tissue biopsy, by providing non-invasive information about the distribution and severity of pathology in the brain.
We propose an ambitious but realistic project which involves the application of state of the art computer processing techniques to in vivo and post mortem MR and to histopathology data, with careful clinical supervision and thorough validation. The partners are leaders in the different disciplines involved and have a track record of successful European cooperation. Existing datasets in patients and in controls are available, and include data where in vivo MR, post mortem (p.m.) MR and p.m. histology have been obtained from the same subject. The initial database will be extended in the project with improved MR acquisition. Computer-assisted quantification of intensity and morphological abnormalities in vivo and p.m. 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 in vivo and p.m. MR and 3-D histology obtained on the same patient, allowing detailed analysis of the distribution of changes in the brain and clarification of the pathological cause of the in vivo 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. One output of the project will be the specification of recommended MR acquisition protocols for future diagnostic use, taking account of the necessary compromise between speed and simplicity for clinical use in confused patients and adequate quality for demonstration of characteristic abnormalities to assist diagnosis.
Funding SchemeCSC - Cost-sharing contracts
06902 Sophia Antipolis
EH4 2XU Edinburgh