Association between Early Ischemic Changes and Collaterals in Acute Stroke: A Retrospective Study.

BACKGROUND AND PURPOSE: The quality of leptomeningeal collaterals may influence the speed of infarct progression in acute stroke. Our main objective was to evaluate the association of leptomeningeal collateral score and its interaction with time with ischemic changes on CT in patients with acute stroke. MATERIALS AND METHODS: Adult patients with acute stroke symptoms and anterior circulation large-vessel occlusion on CTA from 2015 to 2019 were included. Routinely performed NCCT and multiphase CTA were reviewed to assess ASPECTS and the leptomeningeal collateral score. We built multivariate regression models to assess the association between leptomeningeal collateral score and its interaction with time and ASPECTS. Performance measures to predict poor ASPECTS at different time thresholds (identified with receiver operating characteristic curve analysis) were estimated in a subgroup of patients with poor leptomeningeal collateral scores. RESULTS: Leptomeningeal collateral scores 0-1 were associated with lower ASPECTS, and the model with dichotomized and trichotomized leptomeningeal collateral score showed a significant multiplicative interaction between time and the leptomeningeal collateral score. The negative predictive value for poor ASPECTS was >0.9 for at least the first 3 hours from stroke onset to imaging, and the positive predictive value was <0.5 for every time threshold tested in the subgroup of patients with leptomeningeal collateral scores 0-3. CONCLUSIONS: Poor (0-1) leptomeningeal collateral scores were associated with lower ASPECTS, and an increase in time has a multiplicative interaction with the leptomeningeal collateral score on ASPECTS.

Inclusion characterization in a scattering slab with time-resolved transmittance measurements: perturbation analysis.

A procedure for the time-domain optical characterization of an inclusion in a scattering slab is investigated theoretically and experimentally. The method relies on the measurement of a contrast function, which is defined as the time-dependent relative change in the transmitted signal resulting from the presence of the inclusion. Analytical expressions for the contrast functions of absorptive and diffusive inclusions are obtained through a perturbation solution of the diffusion equation. This procedure is used successfully to determine the optical properties of absorptive, diffusive, and mixed inclusions located at midplane in a scattering slab by use of time-resolved transmittance measurements.

Time-domain optical imaging: discrimination between scattering and absorption.

A technique for discriminating between scattering and absorbing inclusions located in the center of a scattering slab is presented. The technique is based on an empirical model that provides a simple mathematical expression to describe the change in the time-resolved transmission resulting from the presence of an inclusion. Experimental results from various configurations show that the technique allows for proper recognition of the type of an inclusion whether it is scattering or absorbing. This technique is a significant step toward tissue differentiation.

Human myoblast transplantation in immunodeficient and immunosuppressed mice: evidence of rejection.

Normal human myoblasts were cloned and transplanted in the tibialis anterior of immunodeficient nude and SCID mice and in mdx mice under different immunosuppressive treatments (cyclosporine A, CsA; antilymphocyte serum, ALS) or not immunosuppressed. This permitted us to show the interaction of the immune system in the myoblast transplantation. The graft success was assessed by verifying signs of humoral and cellular immune reactions and the presence of dystrophin produced by the fusion of the donor myoblasts. This study showed that clones of human myoblasts were able to fuse and produce dystrophin in injected muscles of immunodeficient mice and mdx mice receiving an effective immunosuppressive treatment (i.e., ALS+CsA). However, the same pool of human myoblasts injected in mdx mice inadequately immunosuppressed (i.e., CsA alone or ALS alone) triggered an immune reaction and was rejected. Cells expressing CD4 and CD8 antigens were observed in the injected muscles of mice treated with CsA alone. Therefore, evidence of humoral and cellular rejection was observed following human myoblasts transplantation.

High efficiency of muscle regeneration after human myoblast clone transplantation in SCID mice.

SCID mouse tibialis anterior muscles were first irradiated to prevent regeneration by host myoblasts and injected with notexin to damage the muscle fibers and trigger regeneration. The muscles were then injected with roughly 5 million human myoblasts. 1 mo later, 16-33% of the normal number of muscle fibers were present in the injected muscle, because of incomplete regeneration. However, > 90% of these muscle fibers contained human dystrophin. Some newly formed muscle fibers had an accumulation of human dystrophin and desmin on a part of their membrane. Such accumulations have been demonstrated at neuromuscular junctions before suggesting that the new muscle fibers are innervated and functional. The same pool of clones of human myoblasts produced only < or = 4% of muscle fibers containing human dystrophin when injected in nude mice muscles. Several of the human myoblasts did not fuse and remained in interstitial space or tightly associated with muscle fibers suggesting that some of them have formed satellite cells. Moreover, cultures of 98% pure human myoblasts were obtained from transplanted SCID muscles. In some mice where the muscle regeneration was not complete, the muscle fibers containing human dystrophin also expressed uniformly HLA class 1, confirming that the fibers are of human origin. The presence of hybrid muscle fibers containing human dystrophin and mouse MHC was also demonstrated following transplantation. These results establish that in absence of an immune reaction, transplanted human myoblasts participate to the muscle regeneration with a high degree of efficacy even if the animals were killed only 1 mo after the transplantation.

Utilization of an antibody specific for human dystrophin to follow myoblast transplantation in nude mice.

Human myoblasts were transplanted in nude mice. The efficacy of these transplantations was analyzed using a monoclonal antibody (NCLDys3) specific for human dystrophin. This antibody did not reveal any dystrophin in nude mice that did not receive a human myoblast transplantation. However, about 30 days after a human myoblast transplantation, dystrophin-positive muscle fibers were observed. They were not abundant, and were present either in small clusters or isolated. This technique follows the fate of myoblast transplantation in animals that already have dystrophin, and distinguishes between new dystrophin-positive fibers due to the transplantation and the revertant fibers in mdx mice. Moreover, this technique does not require any labelling of the myoblasts before transplantation. It can also be used to detect dystrophin produced following the fusion of myoblasts transfected with the human dystrophin gene.