Qualitative and quantitative analysis of MR imaging findings in patients with middle cerebral artery stroke implanted with mesenchymal stem cells

Abstract

Background and purpose: Mesenchymal stem cells have potential as a regenerative therapy in ischemic stroke. We sought to determine MR imaging findings after mesenchymal stem cell implantation in chronic middle cerebral artery infarcts and to compare brain volume changes in patients with mesenchymal stem cells with those in age-matched healthy controls and controls with chronic stable MCA infarcts.

Materials and methods: We retrospectively identified 5 patients receiving surgical mesenchymal stem cell implantation to an MCA infarct from January 1, 2005, to July 1, 2013, with MR imaging immediately and 1 year postimplantation. Images at both time points were evaluated for any postimplantation complications. Structural image evaluation using normalization of atrophy software was used to determine volume changes between time points and compare them with those in healthy and age- and sex-matched controls with chronic, stable MCA infarcts by using Kruskal-Wallis and Mann-Whitney U tests.

Results: Susceptibility signal loss and enhancement at the implantation site were seen. No teratoma, tumor, or heterotopia was identified. Volumetric analysis showed a trend toward less overall volume loss after mesenchymal stem cell implantation (0.736; 95% CI, -4.15-5.62) compared with that in age- and sex-matched controls with chronic, stable MCA infarcts (-3.59; 95% CI, -12.3 to -5.21; P = .09), with a significantly greater growth-to-loss ratio in infarcted regions (1.30 and 0.78, respectively, P = .02). A trend toward correlation of growth-to-loss ratio with improvement in physical examination findings was seen (r = 0.856, P = .06).

Conclusions: Postoperative changes consistent with stereotactic implantation were seen, but no teratoma, tumor, or heterotopia was identified. Initial findings suggest a trend toward less volume loss after mesenchymal stem cell implantation compared with that in age- and sex-matched controls with chronic, stable MCA infarcts, with a significantly greater growth-to-loss ratio in the infarcted tissue.

Fig 1.

Calculation of percentage brain volume change and growth-to-loss ratio. A, Brain and skull images are initially each extracted from whole-head input data from the 2 separate time points for each individual subject. The 2 images (1 at each time point) are aligned to each other by using the skull images to constrain registration scaling at each time point. Red demonstrates the common FOV. Green shows the intersection of the 2 standard space brain masks. B, Tissue-type segmentation is used to define the brain/nonbrain boundary. The perpendicular edge displacement at the brain/nonbrain boundary between the 2 time points is estimated, and the mean edge displacement is converted in the estimate of the percentage brain volume change between the 2 points. C and D, The growth-to-loss ratio is calculated in 2 different patients with mesenchymal stem cell implants from the color-rendered image of edge motion superimposed on a half-way image, created by aligning the 2 brain images from the 2 time points to each other by using the skull images to constrain the registration scaling. Red-yellow indicates brain volume increase (white arrowhead), while blue–light blue indicates brain volume decrease (“atrophy”) (white arrow). Regions of growth (red-yellow) are seen to be predominantly at the medial margin of the infarct, where the stem cells are implanted. E and F, Comparable periventricular and cortical regions are shown in healthy controls, demonstrating more red-yellow voxels in similar areas in healthy controls compared with the infarcted regions in patients with MSC implants. The GLR is calculated by tabulating the ratio of the total number of red-yellow voxels (growth areas) to the total number of blue–light blue voxels (areas of volume loss) in the region of the infarct.

Fig 2.

Resolution of enhancement at the implantation site on follow-up imaging. Postcontrast axial echo-spoiled gradient-echo sequence images in a 54-year-old woman status post stem cell implantation demonstrate initial enhancement at the implantation site immediately postoperatively (A), which resolved on 1-year follow-up imaging (B).