Nanoparticles For Delivery Of Rapamycin To Glioblastoma And Glioblastoma-Derived Stem Cells

NANOPARTICLES FOR DELIVERY OF RAPAMYCIN TO GLIOBLASTOMA AND GLIOBLASTOMA-DERIVED STEM CELLS. Kofi-Buaku Atsina1, Jiangbing Zhou1,2, Toral Patel2, Joseph Piepmeier2, and W. Mark Saltzman 1; 1 Yale University, Department of Biomedical Engineering, New Haven, CT; 2 Yale University School of Medicine, Department of Neurosurgery, New Haven, CT· Treatment of glioblastoma remains a challenge primarily because of the difficulty of achieving effective drug delivery, and the relative resistance of cancer stem cells to conventional chemoradiotherapy· Delivery of small molecule drugs, like rapamycin that have shown some efficacy against glioblastoma in in vitro and in vivo studies, is often thwarted by short drug half-lives, systemic toxicity, first-pass metabolism, and the impenetrable blood brain barrier (BBB)· Polymeric nanoparticles have the potential to solve the afore-mentioned challenges by enabling better delivery to cells, stabilizing their contents, and achieving sustained release in a localized fashion · Particularly, ultrasmall nanoparticles improve upon the abilities of this technology by achieving better tumor distribution and cellular uptake· The purpose of this study was to investigate the effects of rapamycin delivery by ultrasmall poly (D,L-lactic-co-glycolic acid)(PLGA) nanoparticles on differentiated glioblastoma (GB) and glioblastoma-derived stem cells (GSCs) in vitro· Ultrasmall polymeric nanoparticles encapsulating rapamycin were fabricated and their effects on GB cells (U87) and GSCs (PS30, PS16, GS5) were examined and compared with free rapamycin· Viability of cells was approximated by measuring their metabolic activity using Thiazolyl Blue Tetrazolium Bromide (MTT) assay. Results demonstrate that rapamycin nanoparticles improve efficacy of delivery relative to free rapamycin as demonstrated by greater inhibition of growth in GB cells, but may also have some efficacy against GSCs

Conversion of Intermediate LIRADS Categories to Hepatocellular Carcinoma in patients with Chronic Hepatitis B: Korean Immigrant Experience

Introduction and Objective The Liver Imaging Reporting and Data System (LIRADS) was created to standardize the reporting and data collection of MR imaging for hepatocellular carcinoma (HCC) in high risk patients. The major categories for LIRADS have the following descriptors: LI-RADS 1 = Definitely benign LI-RADS 2 = Probably benign LI-RADS 3 = Intermediate probability for HCC LI-RADS 4 = Probably HCC LI-RADS 5 = Definitely HCC LI-RADS 5V = Definitely HCC with tumor in vein LI-RADS M = Probable malignancy, not specific for HCC LI-RADS T = Treated Observation However, there is a paucity of quantitative evidence for the progression of LIRADS 2, 3 and 4, (hereafter defined as intermediate LIRADS categories) to LIRADS 5. Our objective was to investigate the conversion of intermediate LIRADS categories to definite hepatocellular carcinoma (LIRADS 5) to help inform management decisions regarding treatment and better stratify imaging follow up for high-risk patients with intermediate LIRADS categories. Poster presented at: SCBT-MR in Salt Lake City, Utah.https://jdc.jefferson.edu/radiologyposters/1002/thumbnail.jp

A Methodology for Systematic Volumetric Analysis of Perioperative Cranial Imaging in Neurosurgical Patients

Background Although objective assessment of perioperative imaging provides a rigorous evaluation method of neurosurgical techniques in epilepsy, its use remains far from mainstream. Open surgery remains the gold standard for treatment of mesial temporal lobe epilepsy (MTLE); however, stereotactic laser ablation is a promising minimally invasive alternative. Nevertheless, the variables that may affect seizure outcome in stereotactic laser amygdalohippocampectomy (SLAH) remain unclear. While an objective endpoint such as ablated mesial temporal volumes may be significant, a standard methodology for calculating such volumes has yet to be proposed. Objectives To formulate and test a methodology, which can aid in critical evaluation of laser trajectories, and ablation cavities in seizure patients. Methods We performed a retrospective study involving 16 patients undergoing SLAH our institution’s approved IRB protocol. Preoperative MRIs were processed and segmented. Postoperative MRIs were co-registered to preoperative MRIs. Laser trajectories and ablation cavities were segmented from this co-registered image. Segmented trajectories, and cavities were superimposed upon the initial MRI. The percentage of each structure affected was calculated, using a voxel by voxel comparison. Results We were successfully able to determine ablation volumes and critically evaluate laser placement. Conclusion This semi-automated methodology showcases a systematic workflow that objectively evaluates perioperative imaging in neurosurgical patients. Pages: 16-2

Longitudinal Qualitative Characterization of MRI Features After Laser Interstitial Thermal Therapy in Drug-Resistant Epilepsy

OBJECTIVE. Laser interstitial thermal therapy (LITT), a method for ablating brain tissue under real-time MR thermometry, has been used more frequently in recent years to treat nonmalignant lesions. The purpose of this study is to longitudinally characterize MRI features after LITT in patients with drug-resistant epilepsy, primarily in the setting of mesial temporal sclerosis. MATERIALS AND METHODS. MR images from 23 consecutive patients who underwent LITT were retrospectively reviewed. All patients had images obtained immediately after the ablation. Multiple patients had follow-up imaging at various time points after treatment, from postoperative days 7 through 1539. A total of 54 MRI studies were reviewed. RESULTS. Immediately after LITT, MR images showed a ring-enhancing lesion at the ablation site with minimal surrounding edema. Seven images showed increased enhancement of the ipsilateral choroid plexus. Images in the subacute phase showed a mild increase in edema with similar enhancement. Images in the transitional phase showed a decrease in edema with variable enhancement. Images in the chronic phase showed minimal gliosis with or without cavity formation or cavity formation alone, with either decreased or no enhancement. CONCLUSION. This report describes the time course of the imaging findings after LITT for drug-resistant epilepsy. The typical stages include rim-enhancing lesion with minimal edema, followed by an increase in edema, to eventual gliosis and nonenhancing cavity formation. Radiologists need to be familiar with the postablation findings to minimize misdiagnosis and prevent unnecessary workup

Highly Visible Wall‐Timer to Reduce Endovascular Treatment Time for Stroke

Background Endovascular therapy for acute ischemic stroke has revolutionized clinical care for patients with stroke and large vessel occlusion, but treatment remains time sensitive. At our stroke center, up to half of the door‐to‐groin time is accounted for after the patient arrives in the angio‐suite. Here, we apply the concept of a highly visible timer in the angio‐suite to quantify the impact on endovascular treatment time. Methods This was a single‐center prospective pseudorandomized study conducted over a 32‐week period. Pseudorandomization was achieved by turning the timer on and off in 2‐week intervals. The primary outcome was angio‐suite‐to‐groin time, and secondary outcomes were angio‐suite‐to‐intubation time, groin‐to‐recanalization time, and 90‐day modified Rankin scale. A stratified analysis was performed based on type of anesthesia (ie, endotracheal intubation versus not). Results During the 32‐week study period, 97 mechanical thrombectomies were performed. The timer was on and off for 38 and 59 cases, respectively. The timer resulted in faster angio‐suite‐to‐groin time (28 versus 33 minutes; P=0.02). The 5‐minute reduction in angio‐suite‐to‐groin was maintained after adjusting for intubation status in a multivariate regression (P=0.02). There was no difference in the 90‐day modified Rankin scale between groups. The timer impact was consistent across the 32‐week study period. Conclusions A highly visible timer in the angio‐suite achieved a meaningful, albeit modest, reduction in endovascular treatment time for patients with stroke. Given the lack of risk and low cost, it is reasonable for stroke centers to consider a highly visible timer in the angio‐suite to improve treatment times