Mouse GBM: A Pilot Collection on NBIA

Introduction
Preclinical Goals
Goal 1: Develop a molecular and imaging based classification for genetically engineered mouse models (GEMs) of glioblastoma multiforme (GBM)
Goal 2: Use imaging to asses response of GBM GEMs to novel therapeutic regimens

Introduction
caBIG® Tools for Preclinical Data
Data from NBIA (National Biomedial Imaging Archive) and caArray (Gene Expression microarrays) are integrated in caIntegrator
NBIA
caArray
caIntegrator
National Biomedical Imaging Archive
Gene expression microarrays
Integrate NBIA, clinical data (survival, IHC…), gene expression

Mouse GBM Pilot Collection
Purpose
Utilize NBIA and caIntegrator to correlate image-based features with ‘clinical’ data in GBM mouse models
Image-based features
Qualitative
Quantitative blood brain barrier permeability
‘Clinical’ features
Genotype
Tumor histologic characteristics
IHC— e.g., CD31
One time imaging in n=62 mouse patients

Mouse GBM Pilot Collection
Animal models
Intracranial injection of cell lines derived from several GEMs
Genotypes:
Rb inactivation + Ras activation (TR)
Rb inactivation + Ras activation + PTEN loss (TRP)
Rb inactivation + Ras activation + EGFR loss (TRE)

Mouse GBM Pilot Collection
Brain Imaging Workflow
4 mice are imaged at once in a Philips Intera Achieva 3.0T MRI clinical scanner ~1hr imagining time? post imaging euthanize and histology
Philips Intera Achieva
3.0T MRI clinical scanner
~1hour imaging time
Four mice imaged
at once
Post imaging euthanize
and histology

Mouse GBM Pilot Collection
MRI Pulse Sequences
T2 weighted pre contrast

Mouse GBM Pilot Collection
MRI Pulse Sequences
T1 weighted pre contrast

Mouse GBM Pilot Collection
MRI Pulse Sequences
T1 weighted post contrast

Mouse GBM Pilot Collection
MRI Pulse Sequences
Dynamic contrast enhanced series

Mouse GBM Pilot Collection
DCEMRI and two compartment model parameters
Quantifiable information on the blood brain barrier permeability is extracted from the pattern of contrast agent uptake
Out-flow/venous
From Cheng Yang

Mouse GBM Pilot Collection
Challenge: Cropping and splitting the image data
Mouse 10
Mouse 11
Mouse 66
Mouse 82

Mouse GBM Pilot Collection
Challenge: Cropping and splitting the metadata
DICOM header

Mouse GBM Pilot Collection
Cropping and splitting the image data
Advantage: Image arrays 16 times smaller

Mouse GBM Pilot Collection
Cropping and splitting the image data

Mouse GBM Pilot Collection
Cropping and splitting the metadata
DICOM header

Mouse GBM Pilot Collection
Deployment to CBIIT instance of NBIA
Demo: Mouse GBM on NBIA

Mouse GBM Pilot Collection
Deployment to CBIIT instance of NBIA

Mouse GBM Pilot Collection
Deployment to CBIIT instance of NBIA

Mouse GBM Pilot Collection
Deployment to CBIIT instance of NBIA

Mouse GBM Pilot Collection
Deployment to CBIIT instance of NBIA

Summary
Progress to date: Successfully deployed individual mouse GBM MRI datasets to NBIA
Next steps
Set up own instance of NBIA
Qualitative and quantitative image analysis
AIM features
Ktrans, ve
Correlation of image-based features with genotype, histology, pathology
caIntegrator

Mouse GBM Pilot Collection
Deployment to CBIIT instance of caInt
Demo: Mouse GBM on caIntegrator