Validation of diffusion tensor imaging measures of nigrostriatal neurons in macaques

• Published in: PloS one Vol. 13; no. 9; p. e0202201
• Main Authors: Shimony, Joshua S, Rutlin, Jerrel, Karimi, Morvarid, Tian, Linlin, Snyder, Abraham Z, Loftin, Susan K, Norris, Scott A, Perlmutter, Joel S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.09.2018; Public Library of Science (PLoS)
• Subjects: Animals; Biology and Life Sciences; Biomarkers; Brain; Brain research; Carotid artery; Comparative analysis; Corpus Striatum - cytology; Corpus Striatum - diagnostic imaging; Correlation analysis; Density; Diagnosis; Diagnostic systems; Diffusion; Diffusion effects; Diffusion Tensor Imaging - methods; Disease Models, Animal; Dopamine; Dopamine receptors; Dopaminergic Neurons - metabolism; Humans; Hydroxylase; Macaca; Magnetic resonance imaging; Male; Medical imaging; Medicine; Medicine and Health Sciences; Mesencephalon; Methods; Monkeys & apes; Movement disorders; MPTP; MPTP Poisoning - diagnostic imaging; MPTP Poisoning - pathology; Neostriatum; Neurodegenerative diseases; Neuroimaging; Neurology; Neurons; Neurosciences; Parkinson disease; Parkinson Disease - diagnostic imaging; Parkinson Disease - pathology; Parkinson's disease; Physiological aspects; Positron emission; Positron emission tomography; Positron-Emission Tomography - methods; Primates; Radioisotopes; Reproducibility of Results; Research and Analysis Methods; Spinal cord; Substantia nigra; Substantia Nigra - cytology; Substantia Nigra - diagnostic imaging; Tomography; Tyrosine; Tyrosine 3-monooxygenase; Tyrosine 3-Monooxygenase - metabolism; United States; United States > US; Missouri
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0202201

Interpretation of diffusion MRI in the living brain requires validation against gold standard histological measures. We compared diffusion values of the nigrostriatal tract to PET and histological results in non-human primates (NHPs) with varying degrees of unilateral nigrostriatal injury induced by MPTP, a toxin selective for dopaminergic neurons. Sixteen NHPs had MRI and PET scans of three different presynaptic radioligands and blinded video-based motor ratings before and after unilateral carotid artery infusion of variable doses of MPTP. Diffusion measures of connections between midbrain and striatum were calculated. Then animals were euthanized to quantify striatal dopamine concentration, stereologic measures of striatal tyrosine hydroxylase (TH) immunostained fiber density and unbiased stereologic counts of TH stained nigral cells. Diffusion measures correlated with MPTP dose, nigral TH-positive cell bodies and striatal TH-positive fiber density but did not correlate with in vitro nigrostriatal terminal field measures or in vivo PET measures of striatal uptake of presynaptic markers. Once nigral TH cell count loss exceeded 50% the stereologic terminal field measures reached a near zero floor effect but the diffusion measures continued to correlate with nigral cell counts. Diffusion measures in the nigrostriatal tract correlate with nigral dopamine neurons and striatal fiber density, but have the same relationship to terminal field measures as a previous report of striatal PET measures of presynaptic neurons. These diffusion measures have the potential to act as non-invasive index of the severity of nigrostriatal injury. Diffusion imaging of the nigrostriatal tract could potentially have diagnostic value in humans with Parkinson disease or related disorders.