OBJECTIVE: To determine the effect of mesenchymal stem cell (MSC) transplantation on diffusion tensor imaging (DTI) metrics from T2-lesional brain tissue in subjects with multiple sclerosis (MS) BACKGROUND: MSCs have potent immunomodulatory, tissue-protective, and repair-promoting properties in vitro and in animal models. The effect of MSCs on T2-lesional tissue in multiple sclerosis (MS) is unknown. DESIGN/METHODS: 24 subjects with relapsing forms of MS, Expanded Disability Status Scale (EDSS) 3.0-6.5, clinical or radiographic disease activity in the prior 2 years, and optic nerve involvement were enrolled into a phase I study of autologous, bone marrow derived, culture-expanded MSCs. MRI studies were performed 2 months prior to and 6 months after MSC transplantation. Lesional tissue regions-of-interest (ROI) were identified as hyperintensity on T2 FLAIR images using automated techniques. Images were subsequently co-registered with DTI data sets from which metrics were derived. Linear mixed effect modeling with likelihood ratio tests and Bonferroni correction was conducted to compare the longitudinal change in DTI metrics prior to and after MSC transplantation. Fixed effects included subject age, size of the ROI and time. Random effects included subject and individual ROI RESULTS: The evolution of DTI metrics showed no significant changes for fractional anisotropy prior to and after MSC transplantation. A progressive loss of longitudinal diffusivity (LD) (-26.6 x10-6mm2/sec/month, p <0.001) in lesional tissue was observed prior to MSC transplantation. Stabilization of LD was observed after MSC transplantation (0.9 x10-6mm2/sec/month, p=0.3). Similar effects were seen with mean and and transverse diffusivity, although the magnitude of these changes was smaller. CONCLUSIONS: MSC resulted in marked changes in DTI metrics from T2-lesional tissue of MS patients. LD has been proposed as a marker of axonal content and the stabilization of LD after MS transplantation may be evidence of decreased axonal loss. Study Supported by: KL2 TR000440/TR/NCATS NIH DoD/CDMRP W81IXWH1010270

April 30, 2014April 8, 2014Free AccessThalamic Volumes and Exposure to Head Trauma in Retired Professional Fighters (P5.315)Charles Bernick, Sarah Banks, Nancy Obuchowski, Wanyong Shin, Mark Lowe, Michael Phillips, Michael Modic, and Stephen JonesAuthors Info & AffiliationsApril 8, 2014 issue82 (10_supplement)https://doi.org/10.1212/WNL.82.10_supplement.P5.315 Letters to the Editor

OBJECT:Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues. The NeuroBlate System incorporates several technological advances to overcome these drawbacks. The authors report a Phase I, thermal dose-escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM).METHODS:Adults with suspected supratentorial rGBM of 15- to 40-mm dimension and a Karnofsky Performance Status score of ≥ 60 were eligible. After confirmatory biopsy, treatment was delivered using a rigid, gas-cooled, side-firing laser probe. Treatment was monitored using real-time MRI thermometry, and proprietary software providing predictive thermal damage feedback was used by the surgeon, along with control of probe rotation and depth, to tailor tissue coagulation. An external data safety monitoring board determined if toxicity at lower levels justified dose escalation.RESULTS:Ten patients were treated at the Case Comprehensive Cancer Center (Cleveland Clinic and University Hospitals-Case Medical Center). Their average age was 55 years (range 34-69 years) and the median preoperative Karnofsky Performance Status score was 80 (range 70-90). The mean tumor volume was 6.8 ± 5 cm(3) (range 2.6-19 cm(3)), the percentage of tumor treated was 78% ± 12% (range 57%-90%), and the conformality index was 1.21 ± 0.33 (range 1.00-2.04). Treatment-related necrosis was evident on MRI studies at 24 and 48 hours. The median survival was 316 days (range 62-767 days). Three patients improved neurologically, 6 remained stable, and 1 worsened. Steroid-responsive treatment-related edema occurred in all patients but one. Three had Grade 3 adverse events at the highest dose.CONCLUSIONS:NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM. CLINICAL TRIAL REGISTRATION NO.: NCT00747253 ( ClinicalTrials.gov ).