Tracking the neurodegeneration of parkinsonian disorders – a pilot study

Abstract

The purpose of the study was to explore the possibilities of using diffusion tensor imaging (DTI) and tractography (DTT) for the differential diagnosis and monitoring of disease progression in idiopathic Parkinson’s disease (IPD), compared with the atypical parkinsonian disorders multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). A 3.0-T MR scanner was used. DTI was acquired using a single-shot EPI sequence with diffusion encoding in 32 directions and a voxel size of 2 × 2 × 2 mm³. DTI data were analysed and DTT was performed using the PRIDE fibre tracking tool supplied by the manufacturer. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) within each tract were determined. DTI and DTT images in patients with moderate to advanced MSA demonstrated degeneration of the middle cerebellar peduncles and pontine crossing tracts, with decreased FA and increased ADC. This accounted for most of the pontine and cerebellar atrophy characteristic of this disease. In contrast, patients with PSP showed a selective degeneration of the superior cerebellar peduncle. Three-dimensional images of whole-brain white matter tracts demonstrated a reduction of cortical projection fibres in all patients with PSP. Visualization of the selective degeneration of individual fibre tracts, using DTI and DTT, adds qualitative data facilitating the differential diagnosis of parkinsonian disorders. Repeated measurements of FA and ADC values in a whole fibre tract might be used for monitoring disease progression and studying the effect of treatment in neuroprotective trials. The results are preliminary considering the small number of subjects in the study.

Appendix: Tractography (continued)

Different voxel comparison parameters were tested by varying the anisotropy threshold and the direction threshold. No improvement in the detection of fibre tracts could be found at different values compared with the values recommended by the software manufacturer. Therefore, an anisotropy threshold with a minimum FA value of 0.3 and deflection threshold 850 (0 full deflection, 1000 no deflection) were used throughout the systematic tractography described here. Attempts to track both major and minor, supratentorial and infratentorial tracts were made, as detailed in the Results. Tracking of the CST, MCP, SCP, PCT, CC and the ILF was performed systematically in all subjects using multiple ROIs. ROIs were always placed perpendicular to the main direction of the tract so that the whole tract would be included. For the CST, tracking was performed between the posterior crus of the internal capsule at the level of the lateral ventricle and the cerebral peduncle or pons. The MCP was tracked both by using multiple ROIs in the coronal plane within the tract on the left and right side, respectively, and by tracking between ROIs placed in the left and right peduncle. Tractography of the ILF was performed between two ROIs in the coronal plane, separated by a distance of 4 mm, going through the PCTs and the central portion of the CC. In the CC, tractography was performed separately in the genu, central portion and splenium, respectively. The average values for the FA and ADC in each tract was calculated and compared between subjects, as well as for repeated measurements in the same subject. For all structures except the CC and PCT, the average FA and ADC values of the left- and right-sided tracts were calculated.