Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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Presentation transcript:

Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert, 2000; Gaurain, 2001; Nonomura, 2001; Guo, 2002; Chen, 2005; Hayashida, 2006; Manenti, 2008; Kinoshita, 2008)  ADC (or mean diffusion) =  cell density (“hypercellularity”)  ADC =  cell density (“hypocellularity”) Viable Tumor (Dark) Necrotic Core Edema ADC Map B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

Diffusion MRI is sensitive to brain tumor cell density Tests at our laboratory have confirmed this relationship - 17 glioma patients (WHO II-IV) underwent diagnostic stereotactic biopsy - Biopsy sites were spatially matched to pre-operative ADC maps R 2 = ; P < B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009From: Ellingson, et al. JMRI 2009, In Press

The Functional Diffusion Map (fDM) (Moffat, 2005; 2006; Hamstra, 2005; 2008) B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 From: Ellingson, JMRI, 2009, In Press

B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2009 SNO/CNS 2009 B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2009 SNO/CNS 2009 B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010From: Ellingson et al. J Neurooncol, 2009, In Press

Early Detection of Brain Tumor Growth T1+C FLAIR fDMs B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 Hypercellular Regions (Blue) Contrast-Enhancement (white)

fDMs in Brain Tumor Progression B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 T1+C FLAIR fDM 3 mo.6 mo.9 mo. (Onset of symptoms)

B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009 fDMs in Progressive Disease (PD)  Hypercellularity

fDM Results in Stable Disease (SD) Treatment: Radiation + Temozolomide B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009

Treatment: Radiation + Temozolomide fDM Results in Responding Disease (RD) B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009

fDM Results in Stable/Responding Disease (SD/RD) B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009  Hypocellularity

fDMs are an early biomarker for cytotoxic and new anti-angiogenic treatments B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 Ellingson BM, J Neurooncol, Under Prep

Results B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009 “fDM Responders” have significantly longer TTP after standard Tx –fDMs are a better predictor than tumor grade

Results B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 SNO/CNS 2009 “fDM Responders” have significantly longer survival on bevacizumab –fDMs are better predictors than grade, age, or mono/combined therapy

Graded fDMs Allow Visualization of Growing Tumor B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, Hypercellular+ Hypocellular 1 Mo.2 Mo.3 Mo.4 Mo.

Graded fDMs Allow Visualization of Growing Tumor B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, Hypercellular+ Hypocellular 7 Mo.5 Mo. 3 Mo.

Graded fDMs Allow Visualization of Growing Tumor B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, Hypercellular+ Hypocellular 5 Mo.4 Mo. 2 Mo.

Hypercellular Hypocellular Macrophages & Inflammatory Cells Demyelination Graded fDMs in Demyelination B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 Biopsy Diagnosis = Demyelination (Multiple Sclerosis) 3 Mo.5 Mo.7 Mo.9 Mo.

Graded fDMs: Radiation Necrosis vs. Tumor B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 Hypercellular Hypocellular T1+C FLAIR Graded fDM

Graded fDMs: Radiation Induced Changes B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 Hypercellular Hypocellular 2 Mo.3 Mo.5 Mo. 8 Mo. 14 Mo. 18 Mo.21 Mo. 23 Mo.

Graded fDMs: Radiation Induced Changes B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 Hypercellular Hypocellular 2 Mo. 4 Mo. 6 Mo. 10 Mo. 14 Mo. 18 Mo.

Graded fDMs Improve Tumor Localization/Grading in Stereotactic Needle Biopsy B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

Graded fDMs Improve Tumor Localization and Grading in Stereotactic Needle Biopsy B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, Lesions Biopsy (WHO II) Hypercellular Hypocellular

Graded fDMs Improve Tumor Localization for Resection B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 Hypercellular Hypocellular Resection Cavity Only 10% of Hypercellular regions were removed!