© nlh national center for image guided therapy, 2012 asnr 2012 imaging genomic mapping of...
TRANSCRIPT
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
ASNR 2012
Imaging Genomic mapping of Edema/Cellular Invasion MRI-Phenotypes in Glioblastoma
Multiforme
PO Zinn1, B Mahajan2, P Sathyan1, S Singh1, S Majumdar1, A Flanders3, E Huang4, R Jain5, D Gutman6, S Hwang6, J Kirby7, J Freyman7, TCGA Glioma Phenotype Research Group, , F Jolesz2, RR Colen2,
1 M.D. Anderson Cancer Center, Houston, TX, USA.2 Brigham and Women's Hospital, Boston, MA, USA.3 Thomas Jefferson University Hospital, Philadelphia, PA, USA.4 National Cancer Institute, Bethesda, MD, USA. 5 Henry Ford, Detroit, MI, USA. 6 Emory University, Atlanta, GA, USA. 7 SAIC-Frederick, Bethesda, MD, USA.
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Disclosure
No Disclosures.
R25 CA089017(RRC) P41 RR019703 (FAJ)
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
• Cellular invasion is one of the major reasons for therapy failure of modern multimodal GBM treatment
• The discovery of targetable genes responsible for cell spread and invasion can be expected to impact modern therapy and patient survival.
Glioblastoma Multiforme
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Imaging genomics
• Imaging genomics has emerged as a new field which links the specific imaging traits (radiophenotypes) with gene-expression profiles.
• We present our paper on the first comprehensive imaging genomic analysis using quantitative MRI volumetrics and large scale gene- and micro-RNA expression profiling in GBM.
• This was first described by our group (Zinn et al PLOSOne 2011) in 2011 where an invasive gene and microRNA was uncovered using the FLAIR volume as an MRI biomarker (radiophenotype).
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Purpose
In this presentation, we seek to demonstrate the imaging-genomic mapping of an invasive MRI radiophenotype, linking MR imaging traits with gene- and miRNA expression profiles, in GBM patients to determine genomic correlates of an edema/invasion MRI radiophenotype
In order to:- DiscoverDiscover new genomic targets for GBM treatment (decreasing
edema/invasion)- PredictPredict key genetic events by MRI- IdentifyIdentify patients who are candidates for the targeted treatment
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
• We retrospective identified 78 treatment naïve GBM patients whom had:• Pre-treatment MRI neuroimaging from The Cancer Imaging
Archive (TCIA)
• Gene- and miRNA- expression profiles The Cancer Genome Atlas (TCGA)
Methods and Materials
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Methods and Materials
• All Image Analysis was performed on Slicer 3.6 (slicer.org)
- The Segmentation module was used to obtain volumes of the peritumoral non-enhancing FLAIR hyperintensity reflecting tumor invasion/edema
- T2/FLAIR was registered to the post- contrast T1WI.
- Volumetric segmentation was performed in a simple hierarchical model of anatomy, proceeding from peripheral to central.
- 3 distinct structures were segmented:• edema/invasion• enhancing tumor• necrosis
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Methods and Materials
Tumor Segmentation. 65 year old male patient with a right temporal GBM. Segmentation of tumor edema (blue), enhancement (yellow) and necrosis (red) was performed and edema volume was obtained.
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Methods and Materials
• Image- Genomic Biostatistics analysis12, 674 genes(22,267 hybridization probes) and 555 microRNAs
(1,510 hybridization probes) were analyzed (Affymetrix/Agilent chip technology) in each patient
• Quantitative edema volumes for each patient (N=78) were obtainedHigh and low groups corresponding to volumes of high and low peritumoral edema/invasion were analyzed/compared for differential genomic expression profiles
• Comparative Marker Selection (Broad Institute) Statistical method to identify preferentially upregulated genomic events in one vs. another predefined patient group (high_low)
• Ingenuity Pathway Analysis (IPA) was used to determine gene ontology
Example of a patient with high edema/tumor infiltrationExample of a patient with high edema/tumor infiltration
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Methods and Materials
High FLAIR RadiophenotypeHigh FLAIR Radiophenotype
Example of a patient with low edema/tumor infiltrationExample of a patient with low edema/tumor infiltration
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Methods and Materials
Low FLAIR Low FLAIR RadiophenotypeRadiophenotype
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Results
Genes associated with invasion were seen in the high FLAIR discovery and validation sets.
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Results
Top concordant genes across discovery and validation sets Top concordant genes across discovery and validation sets
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Results
TOP CONCORDANT MICRORNAS ACROSS DISCOVERY AND VALIDATION SETS
Top Cellular function migration/invasion
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Results
BIOINFORMATICALLY PREDICTED GENE-MICRORNA REGULATORY NETWORKS IN HIGH FLAIR SIGNAL GBMS.
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Results
Our genes and microRNAs were more predictive of patient survival than the current Our genes and microRNAs were more predictive of patient survival than the current subclassification schema used in GBM today.subclassification schema used in GBM today.
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Conclusion
• In this presentation, we present the first comprehensive image- genomic analysis using quantitative MRI volumetrics and large-scale gene- and microRNA expression profiling in GBM
• We identified MRI as a possible screening tool and imaging surrogate for genes and microRNAs involved in GBM cellular migration and invasion
• Specifically, we identified miR-219 and Periostin as a potential therapeutic target against GBM invasion.
© NlH National Center for Image Guided Therapy, 2012
ASNR 2012
Acknowledgements
Helping make cancer history using imaging Helping make cancer history using imaging
Thank you!Thank you!
[email protected]@gmail.com
This work is supported R25 CA089017(RRC), P41 RR019703 (FAJ).
A collaborative project between BWH and M.D. Anderson.