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

R2 = 0.7933; P < 0.001

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 2009B.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 2009B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010 From: 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

HypercellularRegions (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

Hypercellularity

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 Hypocellularity

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, 2010

+ 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, 2010

+ 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, 2010

+ Hypercellular+ Hypocellular

5 Mo.4 Mo.2 Mo.

Hyp

erc

ellu

lar

Hyp

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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

Hyp

erc

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lar

Hyp

oce

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T1+

CF

LAIR

Gra

ded

fDM

Graded fDMs: Radiation Induced Changes

B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

Hyp

erc

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lar

Hyp

oce

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r

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

Hyp

erc

ellu

lar

Hyp

oce

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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 Localizationand Grading in Stereotactic Needle Biopsy

B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

2 LesionsBiopsy (WHO II)

Hyp

erc

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Hyp

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Graded fDMs Improve Tumor Localization for Resection

B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010

Hyp

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Hyp

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ResectionCavity

Only 10% of Hypercellularregions were removed!