Radiogenomic Mapping of Edema/Cellular Invasion MRI-Phenotypes in Glioblastoma Multiforme

Despite recent discoveries of new molecular targets and pathways, the search for an effective therapy for Glioblastoma Multiforme (GBM) continues. A newly emerged field, radiogenomics, links gene expression profiles with MRI phenotypes. MRI-FLAIR is a noninvasive diagnostic modality and was previously found to correlate with cellular invasion in GBM. Thus, our radiogenomic screen has the potential to reveal novel molecular determinants of invasion. Here, we present the first comprehensive radiogenomic analysis using quantitative MRI volumetrics and large-scale gene- and microRNA expression profiling in GBM.Based on The Cancer Genome Atlas (TCGA), discovery and validation sets with gene, microRNA, and quantitative MR-imaging data were created. Top concordant genes and microRNAs correlated with high FLAIR volumes from both sets were further characterized by Kaplan Meier survival statistics, microRNA-gene correlation analyses, and GBM molecular subtype-specific distribution.The top upregulated gene in both the discovery (4 fold) and validation (11 fold) sets was PERIOSTIN (POSTN). The top downregulated microRNA in both sets was miR-219, which is predicted to bind to POSTN. Kaplan Meier analysis demonstrated that above median expression of POSTN resulted in significantly decreased survival and shorter time to disease progression (P<0.001). High POSTN and low miR-219 expression were significantly associated with the mesenchymal GBM subtype (P<0.0001).Here, we propose a novel diagnostic method to screen for molecular cancer subtypes and genomic correlates of cellular invasion. Our findings also have potential therapeutic significance since successful molecular inhibition of invasion will improve therapy and patient survival in GBM

3D ultrasound-based patient positioning for radiotherapy

A new 3D ultrasound-based patient positioning system for target localisation during radiotherapy is described. Our system incorporates the use of tracked 3D ultrasound scans of the target anatomy acquired using a dedicated 3D ultrasound probe during both the simulation and treatment sessions, fully automatic 3D ultrasound-toultrasound registration, and OPTOTRAK IRLEDs for registering simulation CT to ultrasound data. The accuracy of the entire radiotherapy treatment process resulting from the use of our system, from simulation to the delivery of radiation, has been validated on a phantom. The overall positioning error is less than 5mm, which includes errors from estimation of the irradiated region location in the phantom. Copyright 2006 Society of Photo-Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited.Applied Science, Faculty ofElectrical and Computer Engineering, Department ofMechanical Engineering, Department ofReviewedFacult

Non-rigid registration of pre-procedural MR images with intra-procedural unenhanced CT images for improved targeting of tumors during liver radiofrequency ablations.

In the United States, unenhanced CT is currently the most common imaging modality used to guide percutaneous biopsy and tumor ablation. The majority of liver tumors such as hepatocellular carcinomas are visible on contrast-enhanced CT or MRI obtained prior to the procedure. Yet, these tumors may not be visible or may have poor margin conspicuity on unenhanced CT images acquired during the procedure. Non-rigid registration has been used to align images accurately, even in the presence of organ motion. However, to date, it has not been used clinically for radiofrequency ablation (RFA), since it requires significant computational infrastructure and often these methods are not sufficient robust. We have already introduced a novel finite element based method (FEM) that is demonstrated to achieve good accuracy and robustness for the problem of brain shift in neurosurgery. In this current study, we adapt it to fuse pre-procedural MRI with intra-procedural CT of liver. We also compare its performance with conventional rigid registration and two non-rigid registration methods: b-spline and demons on 13 retrospective datasets from patients that underwent RFA at our institution. FEM non-rigid registration technique was significantly better than rigid (p \u3c 10-5), non-rigid b-spline (p \u3c 10-4) and demons (p \u3c 10-4) registration techniques. The results of our study indicate that this novel technology may be used to optimize placement of RF applicator during CT-guided ablations

Evaluation of brain image nonrigid registration algorithms based on Log-Euclidean MR-DTI consistency measures

Several nonrigid registration algorithms have been proposed for inter-subject alignment, used to construct statistical atlases and to identify group differences. Assessment of the accuracy of nonrigid registration algorithms is an essential and complex issue due to its intricate framework and its application-dependent behavior. We demonstrate that the diffusion MRI provides an independent means of assessing the quality of alignment achieved on the structural MRI. Diffusion tensor MRI (DT MRI) enables the comparison of the local position and orientation of regions that appear homogeneous in conventional MRI. We carried out inter-subject alignment of conventional T1-weighted MRI with three different registration algorithms. Consequently, we projected DT MRI of each subject through the same inter-subject transformation. The quality of the inter-subject alignment is assessed by estimating the consistency of the aligned DT-MRI using the Log-Euclidean framework