Objective: Explore changes in correlations between brain perfusion and UPDRS-Total (UPDRS-T) after a single infusion of allogeneic bone marrow-derived mesenchymal stem cells (MSC).

Background: Our phase I trial has found MSC infusion to treat Parkinson’s disease to be safe [1], however the effects of changes in brain perfusion remains to be explored.

Method: 20 patients with mild/moderate PD had 3T MRI including pulsed, continuous arterial spin labelling at baseline and 6 months after MSC infusion dose of 1,3, 6, or 10 x 10⁶ MSC/kg (5 patients per dose). Data were analyzed with ExploreASL v1.21 [2], producing for each participant at each time whole-brain voxel-level maps (1.5 mm³ resolution) of cerebral blood flow (CBF). Correlation differences as a function of time between CBF maps and UPDRS-T were explored using linear mixed-effects modeling with AFNI’s 3dLME [3] using a combined height (p<0.05) and cluster extent (80 voxels) threshold.

Results: UPDRS improved significantly (t₍₁₉₎=-6.22, p<0.0001) from a mean of 50.4 (std 17.19) at baseline to 29.60 (std 11.42) after 6 months. Two voxel-level perfusion patterns were identified. In the first pattern, which included a total 733 voxels encompassing 6 different regions (mean 122, std 36), perfusion decreased as a function of total UPDRS at baseline but increased as a function of total UPDRS after 6 months. In the second pattern, which included a total 2254 voxels encompassing 20 different regions (mean 112, std 31), perfusion increased as a function of total UPDRS at baseline but decreased as a function of total UPDRS after 6 months. The first pattern included right putamen, pallidum, middle frontal gyrus, anterior cingulate, and left cerebellum. The second pattern included right inferior temporal gyrus, lingual gyrus, inferior frontal gyrus, precuneus, and left fusiform, cerebellum, thalamus, and substantia nigra/red nucleus.

Conclusion: Exploratory analyses identified three times more voxels exhibiting higher perfusion 6 months after MSC infusion. The shift in more voxels showing higher perfusion as a function of higher UPDRS-T score at baseline to higher perfusion as a function of lower UPDRS-T after 6 months may be an important marker of improved brain function after the stem cell treatment. Replication in larger samples examining the dose-response relationship are needed before drawing firm conclusions.

References: 1. Schiess, M.C., Suescun, J., Doursout, M., Adams, C., Green, C., Saltarrelli, J.G., Savitz, S., Ellmore, T.M., (2021) Allogeneic bone marrow-derived mesenchymal stem cells safety in idiopathic Parkinson’s disease. Movement Disorders, Mar 2, 2021; (accepted).

2. Mutsaerts, H.J., Petr, J., Groot, P., Vandemaele, P., Ingala, S., Robertson, A.D., Václavů, L., Groote, I., Kuijf, H., Zelaya, F. and O’Daly, O., 2020. ExploreASL: an image processing pipeline for multi-center ASL perfusion MRI studies. NeuroImage, 219, p.117031.

3 Chen, G., Saad, Z.S., Britton, J.C., Pine, D.S., Cox, R.W. (2013). Linear
Mixed-Effects Modeling Approach to FMRI Group Analysis. NeuroImage 73:176-190.
http://dx.doi.org/10.1016/j.neuroimage.2013.01.047

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-brain-perfusion-changes-correlated-with-updrs-total-in-a-phase-i-mesenchymal-stem-cell-trial-for-parkinsons-disease/