Diffusion Physics
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Transcript of Diffusion Physics
Diffusion Physics
H2O in the body is always in random motion due to thermal agitation
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Detecting Diffusion with MRI - Intravoxel Incoherent Motion
Ellingson et al., Concepts in MR, 2008
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010 From: Ellingson, Concepts in MR, 2008
Detecting Diffusion with MRI - Intravoxel Incoherent Motion
Detected DWI Signal
MRI Signal w/o Diffusion Sensitivity
Variability inPhase of “Tagged” H2O Level of Diffusion Weighting
Diffusion Coefficient
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Proton on H2O
Image Voxel = t1
= t2
= t3
MR
I Sig
nal
Diffusion Time (or level of diffusion weighting)
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
• Apparent diffusion coefficient (ADC) measured clinically reflects extracellular water• ADC is dependent on tumor cell density
(Ellingson, 2010; Sugahara, 1999; Lyng, 2000; Chenevert, 2000; Gaurain, 2001; Nonomura, 2001; Guo, 2002; Chen, 2005; Hayashida, 2006; Manenti, 2008;
Kinoshita, 2008
Cell Density (hypercellular) = ADC Cell Density (hypocellular) = ADC
Diffusion MR Characteristics of theCentral Nervous System
Viable Tumor (Dark)
Necrotic Core
Edema
ADC Map
From: Ellingson, J Magn Reson Imaging, 2010B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Diffusion MRI During Successful Cytotoxic Therapy
From: Ross, Mol Cancer Ther, 2003B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
The Functional Diffusion Map (fDM)(Moffat, 2005; 2006; Hamstra, 2005; 2008; Ellingson, 2010)
From: Ellingson, JMRI, 2010
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Early Detection of Brain Tumor Growth
T1+C
FLAIR
fDMs
HypercellularRegions (Blue)
Contrast-Enhancement(white)
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
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, 2010
From: Ellingson, ISMRM, 2009; SNO, 2009B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
fDMs in Progressive Disease (PD)
Hypercellularity
Hypercellularity
Hypercellularity
Positive Tumor Response to TreatmentDay 89 Day 180 Day 237 Day 298
HypercellularTumor
Hypocellular“Treated” Tumor
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010 From: Ellingson, ISMRM, 2009; SNO, 2009
From: Ellingson, ISMRM, 2009; SNO, 2009B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
fDM Results in Stable/Responding Disease (SD/RD)
Hypocellularity Hypocellularity
Hypocellularity
From: Ellingson, ISMRM, 2009; SNO, 2009B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
fDMs May Reflect Molecular/Genetic Phenotypes
MGMT(+) MGMT(+) MGMT(+)MGMT(-) MGMT(-) MGMT(-)
(n = 50 Total Patients)
Spearman Corr. Coeff. R = 0.4350, P = 0.0016
Clinical fDM Sensitivity/Specificity
WHO Grade
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010 From: Ellingson BM et al., ISMRM, 2010
(n = 50 Total Patients)
Pearson Corr. Coeff.R2 = 0.8586, P < 0.0001
Clinical fDM Sensitivity/Specificity
Neurological Status
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010 From: Ellingson BM et al., ISMRM, 2010
fDMs as an early biomarker for cytotoxic and new anti-angiogenic treatments
From: Ellingson BM, J Neuroonc, 2010B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Volumetric Analysis of fDMs as an early biomarker for cytotoxic and new anti-angiogenic treatments
From: Ellingson BM, J Neuroonc, 2010
fDMs detect PD > 2 months before recurrence
Bevacizumab Temozolomide
fDMs predict survival and progression better than age and tumor grade!
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Better Defining ADC Thresholds for Classification
From: Ellingson, JMRI, 2010
ADC =
95%
C.I.
NAW
M
ADC =
95%
C.I.
NAGM
ADC =
95%
C.I.
NAW
M+N
AGM
ADC =
95%
C.I.
NAW
M+N
AGM+C
SF
Different ADC thresholds reflect different sensitivity/specificity to growing tumor
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Better Defining ADC Thresholds for Classification
From: Ellingson, JMRI, 2010
Different ADC thresholds reflect different sensitivity/specificity to growing tumor
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Graded fDMs Allow Visualization and Quantification of Growing Tumor
+ Hypercellular+ Hypocellular
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Biological Calibration
From: Ellingson, JMRI, 2010
Graded fDMs Allow Better Visualization of Growing Tumor
+ Hypercellular+ Hypocellular
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Graded fDMs Allow Better Visualization of Growing Tumor
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
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, 2010
Graded fDMs can distinguish radiation necrosis from tumor
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, 2010
Diffusivity Mismatch Index (DMI) predicts survival
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010 From: Ellingson, Clin Cancer Res, 2010, Submitted
Diffusivity Mismatch Index (DMI) predicts survival
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010 From: Ellingson, Clin Cancer Res, 2010, Submitted
Cell Invasion, Migration, and Proliferation Level Estimates = CIMPLE Maps
• Higher-order changes in ADC over time and space• Allows us to map estimates of invasion and proliferation
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010 From: Ellingson, Magn Reson Med, 2010, Accepted
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Whole Brain CIMPLE Maps & 18F-FDOPA PET
From: Ellingson, Magn Reson Med, 2010, Accepted
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Whole Brain CIMPLE Maps & 18F-FDOPA PET
-10Cell Proliferation
[1/yr]
10
CIMPLE Maps Pre-Tx Post-Tx Recurrence
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010 From: Ellingson, Cancer Imaging, 2010, Submitted
CIMPLE Maps(Doubling Times)
Doubling Time
Days 3650
Within physiologic range of doubling times:
• 22 days (GBM) - 556 days (WHO II)
Blankenberg et al, AJNR, 2005
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
CIMPLE Maps(Doubling Times)
Doubling Time
Days 3650
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Doubling Time (Days)
50< 10 403020
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Mean proliferation at start of treatment predicts survival(defined from time of CIMPLE map) N = 26
From: Ellingson, Cancer Imaging, 2010, Submitted
Conclusions
• Diffusion MRI is sensitive to cell density
• Functional diffusion maps (fDMs) reflect voxel-by-voxel changes in cellularity
• fDM kinetics are useful for individual patient monitoring
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
• Graded fDMs allow for degree of cellularity to be visualized and quantified (biological basis)
• Graded fDMs can distinguish radiation necrosis from tumor recurrence
• CIMPLE maps allow visualization and quantification of invasion and proliferation rates
Conclusions
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Radiology• Whitney Pope, M.D., Ph.D.• Dieter Enzmann, M.D.• Jonathan Goldin, M.D.• MedQIA
Neurology/Neuro-Oncology• Timothy Cloughesy, M.D.• Albert Lai, M.D., Ph.D.
Neurosurgery• Linda Liau, M.D.• Bob Shafa, M.D.• Antonio DeSalles, M.D.
Pathology• Paul Mischel, M.D.• Bill Yong, M.D.
Thank You!
B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLA, 2010
Radiology• Kathleen Schmainda, Ph.D.• Scott Rand, M.D., Ph.D.
Neurology/Neuro-Oncology• Mark Malkin, M.D.• Jennifer Connelly, M.D.
Neurosurgery• Wade Mueller, M.D.• Shekar Kurpad, M.D., Ph.D.