Objective: To determine the best diffusion tensor imaging markers of dopaminergic and serotonergic lesions in the non-human primate.

Background: DTI has received particular interest to highlight early markers of neurodegeneration. In Parkinsonian patients, correlations have been evidenced between the motor symptomatology and the alteration of diffusional parameters within the substantia nigra where DA cell bodies are lost. However, neurodegenerative processes can also involve the 5-HT system and Parkinsonian patients may exhibit different lesion profiles according to the variety of motor and non-motor symptoms expressed.

Methods: DA and 5-HT lesions were modelled in monkeys by sequential use of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MDMA (3,4-methylene-dioxy-methamphetamine; better known as ecstasy). We confronted longitudinal measures of mean diffusivity (MD) and fractional anisotropy (FA) with severity of parkinsonism, PET imaging analyses and post-mortem fibers quantification.

Results: The MPTP-induced lesion was associated to increases of MD in target structures notably within the caudate nucleus, ventral striatum, and the anterior cingulate cortex. These DTI variations discriminated the moderately and severely lesioned monkeys and reflected profound alterations of DA and/or 5-HT fibers. MD increase within the anterior cingulate cortex also correlated with nigral cell bodies loss and severity of parkinsonism, while MD increase within the caudate correlated with [18F]DOPA caudate uptake. Interestingly also, these DTI alterations were reduced by the compensatory sprouting taking place in moderately lesioned monkeys. The MDMA-induced lesion caused an opposite pattern of DTI alterations with an increased FA within basal ganglia, the one within the caudate nucleus correlating with the Parkinsonian score. Here again, DTI variations reflected profound alterations of 5-HT fibers. Finally, the confrontation of DTI measures within key structures discriminated between single (MPTP) and double (MPTP/MDMA) lesioned monkeys.

Conclusions: Taken together, these results demonstrate that DTI within the caudate nucleus characterize both severity and specificity of lesions. They further highlight DTI measures within this brain region as key markers to reveal specific patterns of lesion in Parkinsonian patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/diffusion-tensor-imaging-dti-within-the-primate-caudate-nucleus-marks-dopaminergic-da-and-serotonergic-5-ht-lesions/