Functional Diffusion Maps (fDMs) for Brain Tumor Treatment Response Monitoring

Functional Diffusion Maps (fDMs)for Brain Tumor Treatment Response Monitoring

Benjamin M. Ellingson, Ph.D.Assistant Professor of RadiologyDept. of Radiological Sciences

David Geffen School of Medicine at UCLA

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

Diffusion MRI is sensitive to 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; Ellingson, 2010)

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 Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

ADC correlates with brain tumor cell density

Untreated glioma patients (WHO II-IV) underwent diagnostic stereotactic biopsy (n = 17) biopsy sites were spatially matched to the pre-operative ADC map

R2 = 0.7933; P < 0.001

ADC Sensitivity = 1.01 x 10-7 [mm2/s]/[nuclei/mm2]

From: Ellingson BM et al., J Magn Reson Imaging, 2010B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

From: Ellingson, JMRI, 2009, In Press

The Functional Diffusion Map (fDM)(Moffat, 2005; 2006; Hamstra, 2005; 2008; Ellingson, 2009; 2010; 2011)

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

From: Ellingson, JMRI, 2009, In PressB.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

The Functional Diffusion Map (fDM)(Moffat, 2005; 2006; Hamstra, 2005; 2008; Ellingson, 2009; 2010; 2011)

Early Detection of Brain Tumor Growth

T1+C

FLAIR

fDMs

Contrast-Enhancement(white)

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

fDMs in Brain Tumor Progression

T1+C

FLAIR

fDM

3 mo. 6 mo. 9 mo. (Onset of symptoms)

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

From: Ellingson, ISMRM, 2009; SNO, 2009

fDMs in Progressive Disease (PD)

Hypercellularity

Hypercellularity

Hypercellularity

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

From: Ellingson, ISMRM, 2009; SNO, 2009

fDM Results in Stable/Responding Disease (SD/RD)

Hypocellularity Hypocellularity

Hypocellularity

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

From: Ellingson, ISMRM, 2009; SNO, 2009

fDMs May Reflect Molecular/Genetic Phenotypes

MGMT(+) MGMT(+) MGMT(+)MGMT(-) MGMT(-) MGMT(-)

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

From: Ellingson, ISMRM, 2009; SNO, 2009

fDMs May Reflect Molecular/Genetic Phenotypes

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

(n = 50 Total Patients)

Spearman Corr. Coeff. R = 0.4350, P = 0.0016

Clinical fDM Sensitivity/Specificity

WHO Grade

From: Ellingson BM et al., ISMRM, 2010B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

(n = 50 Total Patients)

Pearson Corr. Coeff.R2 = 0.8586, P < 0.0001

Clinical fDM Sensitivity/Specificity

Neurological Status

From: Ellingson BM et al., ISMRM, 2010B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

fDMs Before/After Radiotherapy

N = 94

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

fDMs Before/After Bevacizumab

N = 77

Graded fDMs

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

Graded fDMs:Tumor Invasion Beyond FLAIR

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

Graded fDMs for StealthStation™ Biopsy Localization

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

Hyp

erc

ellu

lar

Hyp

oce

llula

r

Macrophages& Inflammatory Cells Demyelination

Graded fDMs in Differential DiagnosisTumor vs. Demyelination

Biopsy Diagnosis = Demyelination (Multiple Sclerosis)

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

Graded fDMs – Radiation Necrosis

Hyp

erc

ellu

lar

Hyp

oce

llula

r

T1+

CF

LAIR

Gra

ded

fDM

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011

Stereotactic fDMs Using a Neuroanatomical Atlas

AnatomyLabelMap

OverlaidOnT1 Atlas

B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2011