Publications by Year: 2014

Jong Woo Lee, Andrew D Norden, Keith L Ligon, Alexandra J Golby, Rameen Beroukhim, John Quackenbush, William Wells, Kristen Oelschlager, Derek Maetzold, and Patrick Y Wen. 2014. “Tumor Associated Seizures in Glioblastomas are Influenced by Survival Gene Expression in a Region-specific Manner: A Gene Expression Imaging Study.” Epilepsy Res, 108, 5, Pp. 843-52.Abstract

Tumor associated seizures (TAS) are common and cause significant morbidity. Both imaging and gene expression features play significant roles in determining TAS, with strong interactions between them. We describe gene expression imaging tools which allow mapping of brain regions where gene expression has significant influence on TAS, and apply these methods to study 77 patients who underwent surgical evaluation for supratentorial glioblastomas. Tumor size and location were measured from MRI scans. A 9-set gene expression profile predicting long-term survivors was obtained from RNA derived from formalin-fixed paraffin embedded tissue. A total of 32 patients (42%) experienced preoperative TAS. Tumor volume was smaller (31.1 vs. 58.8 cubic cm, p<0.001) and there was a trend toward median survival being higher (48.4 vs. 32.7 months, p=0.055) in patients with TAS. Although the expression of only OLIG2 was significantly lower in patients with TAS in a groupwise analysis, gene expression imaging analysis revealed regions with significantly lower expression of OLIG2 and RTN1 in patients with TAS. Gene expression imaging is a powerful technique that demonstrates that the influence of gene expression on TAS is highly region specific. Regional variability should be evaluated with any genomic or molecular markers of solid brain lesions.

Muna Aryal, Costas D Arvanitis, Phillip M Alexander, and Nathan McDannold. 2014. “Ultrasound-Mediated Blood-brain Barrier Disruption for Targeted Drug Delivery in the Central Nervous System.” Adv Drug Deliv Rev, 72, Pp. 94-109.Abstract

The physiology of the vasculature in the central nervous system (CNS), which includes the blood-brain barrier (BBB) and other factors, complicates the delivery of most drugs to the brain. Different methods have been used to bypass the BBB, but they have limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the BBB at discrete targets. This review provides insight on the current status of this unique drug delivery technique, experience in preclinical models, and potential for clinical translation. If translated to humans, this method would offer a flexible means to target therapeutics to desired points or volumes in the brain, and enable the whole arsenal of drugs in the CNS that are currently prevented by the BBB.

Ehud J Schmidt, Zion TH Tse, Tobias R Reichlin, Gregory F Michaud, Ronald D Watkins, Kim Butts-Pauly, Raymond Y Kwong, William Stevenson, Jeffrey Schweitzer, Israel Byrd, and Charles L Dumoulin. 2014. “Voltage-based Device Tracking in a 1.5 Tesla MRI during Imaging: Initial Validation in Swine Models.” Magn Reson Med, 71, 3, Pp. 1197-209.Abstract

PURPOSE: Voltage-based device-tracking (VDT) systems are commonly used for tracking invasive devices in electrophysiological cardiac-arrhythmia therapy. During electrophysiological procedures, electro-anatomic mapping workstations provide guidance by integrating VDT location and intracardiac electrocardiogram information with X-ray, computerized tomography, ultrasound, and MR images. MR assists navigation, mapping, and radiofrequency ablation. Multimodality interventions require multiple patient transfers between an MRI and the X-ray/ultrasound electrophysiological suite, increasing the likelihood of patient-motion and image misregistration. An MRI-compatible VDT system may increase efficiency, as there is currently no single method to track devices both inside and outside the MRI scanner. METHODS: An MRI-compatible VDT system was constructed by modifying a commercial system. Hardware was added to reduce MRI gradient-ramp and radiofrequency unblanking pulse interference. VDT patches and cables were modified to reduce heating. Five swine cardiac VDT electro-anatomic mapping interventions were performed, navigating inside and thereafter outside the MRI. RESULTS: Three-catheter VDT interventions were performed at >12 frames per second both inside and outside the MRI scanner with <3 mm error. Catheters were followed on VDT- and MRI-derived maps. Simultaneous VDT and imaging was possible in repetition time >32 ms sequences with <0.5 mm errors, and <5% MRI signal-to-noise ratio (SNR) loss. At shorter repetition times, only intracardiac electrocardiogram was reliable. Radiofrequency heating was <1.5°C. CONCLUSION: An MRI-compatible VDT system is feasible.