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”)
Edema
Necrotic
Core
Viable
Tumor
(Dark)
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
From: Ellingson, et al. JMRI 2009, In Press
SNO/CNS 2009
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
B.M.
Ellingson,
Ph.D.,
Dept.
of Radiology,
Medical
College
of Wisconsin,
2010
SNO/CNS 2009
B.M.
Ellingson,
Ph.D.,
Dept.
of Radiology,
Medical
College
of Wisconsin,
2009
B.M.
Ellingson,
Ph.D.,
Dept.
of Radiology,
Medical
College
of Wisconsin,
2010
2009
From: Ellingson et al. J Neurooncol, 2009, InSNO/CNS
Press
Early Detection of Brain Tumor Growth
T1+C
FLAIR
Contrast-Enhancement
(white)
Hypercellular
Regions (Blue)
fDMs
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
fDMs in Brain Tumor Progression
3 mo.
T1+C
FLAIR
fDM
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
6 mo.
9 mo. (Onset of symptoms)
fDMs in Progressive Disease (PD)
Hypercellularity
Hypercellularity
Hypercellularity
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
SNO/CNS 2009
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
fDM Results in Responding Disease (RD)
Treatment:
Radiation + Temozolomide
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
SNO/CNS 2009
fDM Results in Stable/Responding Disease
(SD/RD)
Hypocellularity
Hypocellularity
Hypocellularity
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
SNO/CNS 2009
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
• “fDM Responders” have significantly longer TTP after standard Tx
– fDMs are a better predictor than tumor grade
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
SNO/CNS 2009
Results
• “fDM Responders” have significantly longer survival on bevacizumab
– fDMs are better predictors than grade, age, or mono/combined therapy
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
SNO/CNS 2009
Graded fDMs Allow Visualization of Growing Tumor
1 Mo.
2 Mo.
+ Hypocellular
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
3 Mo.
4 Mo.
+ Hypercellular
Graded fDMs Allow Visualization of Growing Tumor
5 Mo.
3 Mo.
+ Hypocellular
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
7 Mo.
+ Hypercellular
Graded fDMs Allow Visualization of Growing Tumor
4 Mo.
2 Mo.
+ Hypocellular
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
5 Mo.
+ Hypercellular
Graded fDMs in Demyelination
5 Mo.
7 Mo.
9 Mo.
Hypocellular
Hypercellular
3 Mo.
Macrophages
& Inflammatory Cells
Demyelination
Biopsy Diagnosis =
Demyelination (Multiple Sclerosis)
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
Hypercellular
Hypocellular
Graded
fDM
FLAIR
T1+C
Graded fDMs: Radiation Necrosis vs. Tumor
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
Graded fDMs: Radiation Induced Changes
2 Mo.
18 Mo.
5 Mo.
21 Mo.
8 Mo.
23 Mo.
Hypocellular
Hypercellular
14 Mo.
3 Mo.
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
Graded fDMs: Radiation Induced Changes
2 Mo.
14 Mo.
6 Mo.
18 Mo.
Hypocellular
Hypercellular
10 Mo.
4 Mo.
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
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 Localization
and Grading in Stereotactic Needle Biopsy
2 Lesions
Hypocellular
Hypercellular
Biopsy (WHO II)
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010
Graded fDMs Improve Tumor Localization for Resection
Hypocellular
Only 10% of Hypercellular
regions were removed!
Hypercellular
Resection
Cavity
B.M. Ellingson, Ph.D., Dept. of Radiology, Medical College of Wisconsin, 2010