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