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Page 1: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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

Page 2: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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

Page 3: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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

Page 4: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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

Page 5: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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

Page 6: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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)

Page 7: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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)

Page 8: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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

fDMs in Progressive Disease (PD)

Hypercellularity

Hypercellularity

Hypercellularity

Page 9: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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

Page 10: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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

Page 11: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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

Page 12: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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

Page 13: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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

Page 14: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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

Page 15: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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.

Page 16: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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.

Page 17: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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.

Page 18: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

Hyp

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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.

Page 19: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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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Hyp

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T1+

CF

LAIR

Gra

ded

fDM

Page 20: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

Graded fDMs: Radiation Induced Changes

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

Hyp

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Hyp

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2 Mo. 3 Mo. 5 Mo. 8 Mo.

14 Mo. 18 Mo. 21 Mo. 23 Mo.

Page 21: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

Graded fDMs: Radiation Induced Changes

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

Hyp

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Hyp

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2 Mo. 4 Mo. 6 Mo.

10 Mo. 14 Mo.18 Mo.

Page 22: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

Graded fDMs Improve Tumor Localization/Grading in Stereotactic Needle Biopsy

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

Page 23: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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

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Hyp

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Page 24: Diffusion MRI is sensitive to brain tumor cell density Clinical ADC and cell density are negatively correlated (Sugahara, 1999; Lyng, 2000; Chenevert,

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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ResectionCavity

Only 10% of Hypercellularregions were removed!


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