Topologically dissociable patterns of development of the human cerebral cortex.

Over 90 years ago, anatomists noted the cortex is thinner in sulci than gyri, suggesting that development may occur on a fine scale driven by local topology. However, studies of brain development in youth have focused on describing how cortical thickness varies over large-scale functional and anatomic regions. How the relationship between thickness and local sulcal topology arises in development is still not well understood. Here, we investigated the spatial relationships between cortical thickness, folding, and underlying white matter organization to elucidate the influence of local topology on human brain development. Our approach included using both T1-weighted imaging and diffusion tensor imaging (DTI) in a cross-sectional sample of 932 youths ages 8-21 studied as part of the Philadelphia Neurodevelopmental Cohort. Principal components analysis revealed separable development-related processes of regionally specific nonlinear cortical thickening (from ages 8-14) and widespread linear cortical thinning that have dissociable relationships with cortical topology. Whereas cortical thinning was most prominent in the depths of the sulci, early cortical thickening was present on the gyri. Furthermore, decline in mean diffusivity calculated from DTI in underlying white matter was correlated with cortical thinning, suggesting that cortical thinning is spatially associated with white matter development. Spatial permutation tests were used to assess the significance of these relationships. Together, these data demonstrate that cortical remodeling during youth occurs on a local topological scale and is associated with changes in white matter beneath the cortical surface.

Impact of adipose-derived stem cells on aortic tensile strength in a model of abdominal aortic aneurysm.

Introduction: Abdominal Aortic Aneurysm (AAA) is a highly morbid condition and is the 11th leading cause of death in the United States. Treatment options are limited to operative interventions, with minimal non-operative options. Prior literature has demonstrated a benefit to the use of mesenchymal stem cells (MSCs) in attenuating AAA formation. We demonstrate the utility of MSCs in treating AAA in swine, focusing on the mechanical and structural characteristics of aortic tissue after treatment. Methods: 16 Yorkshire pigs underwent retroperitoneal exposure of the infrarenal aorta, with subsequent induction of AAA with peri-adventitial elastase and collagenase. A 1 × 4 cm piece of Gelfoam, an absorbable gelatin-based hemostatic agent, was soaked in media or human MSCs and placed directly on the vessel for control and experimental animals. At postoperative day 21, animals were sacrificed and the infrarenal aorta at this location was harvested for analysis. Tensile strength was measured using a tensiometer, from which Young's modulus and maximum strain were calculated. Results: All animals survived the surgery and post-operative course. Young's elastic modulus for the aneurysm control group was 15.83 ± 1.61 compared to 22.13 ± 2.34 for the stem cell treated segment, p = 0.0316. There was no significant difference in the peak stress between groups. Conclusions: This is the first study to demonstrate the mechanical effects of stem cell therapy on a model of AAA in swine. Young's modulus, which characterizes the intrinsic capacity of a tissue to withstand stress, was greater in the animals treated with MSCs compared to control animals with aneurysms. This methodology can be utilized in future large animal models to develop cell and drug-based therapies for AAA.

Recurrent Gastrointestinal Stromal Tumors in the Imatinib Mesylate Era: Treatment Strategies for an Incurable Disease.

INTRODUCTION: Recurrence of gastrointestinal stromal tumors (GISTs) after surgical resection and imatinib mesylate (IM) adjuvant therapy poses a significant treatment challenge. We present the case of a patient who underwent surgical resection after recurrence and review the current literature regarding treatment. CASE PRESENTATION: A 58-year-old man with a large intra-abdominal jejunal GIST was treated with complete surgical resection followed by IM. The patient experienced disease recurrence 3.5 years later and underwent IM dose escalation and reresection. CONCLUSION: Current strategies to treat recurrent GIST include dose escalation, modifying adjuvant tyrosine kinase inhibitor therapy, and surgery. High-level evidence will be required to better define the combinatory roles of tyrosine kinase inhibitor therapy, guided by molecular profiling, and surgery in the management of recurrent GIST.