patrick j. bolan assistant professor center for magnetic resonance research, dept radiology
DESCRIPTION
Patrick J. Bolan Assistant Professor Center for Magnetic Resonance Research, Dept Radiology University of Minnesota. Radiology/BME collaborators: Mike Garwood, Kamil Ugurbil , Greg Metzger, Tommy Vaughan Clinical collaborators: Mike Nelson, Tim Emory, Doug Yee, radiology residents - PowerPoint PPT PresentationTRANSCRIPT
Patrick J. BolanAssistant Professor
Center for Magnetic Resonance Research, Dept RadiologyUniversity of Minnesota
Center for MR Research UM Medical Center – Fairview
Radiology/BME collaborators: Mike Garwood, Kamil Ugurbil, Greg Metzger, Tommy Vaughan
Clinical collaborators: Mike Nelson, Tim Emory, Doug Yee, radiology residents
My group: Timo Liimatainen (postdoc), Leighton Warmington (BPhys MS), Avani Chandresekaran (CS MS)
Areas of Research
• Breast MR imaging and spectroscopy
• Evaluating cancer treatment response
• High-field Body MR Technique
3T 4T 7T
Breast MR Spectroscopy
lipids
suppressed water
lipid
Cholinecompounds
(tCho)
Frequency (ppm)
Single-Voxel 1H MRS
invasive ductal carcinoma
Contrast-enhanced MRI
High [tCho] cancer (proliferation, cell density, upgragulated transport & kinase activity)
Diagnosing Suspicious Lesions at 4T
0
2
4
6
8
10
Malignant (n=58) Benign (n=54) Normal (n=5)
[tCho
] (m
mol
/kg
)
ROC cutoff = 1.0 mmol/kgsensitivity 72%specificity 83%
ROC cutoff = 1.0 mmol/kgsensitivity 72%specificity 83%
Haddadin et al., NMR Biomed 2009
Treatment Monitoring with MRS
• Size changes takes weeks, metabolic take hours
• [tCho] as a Predictive Biomarker– switch drugs / treatment strategy– evaluate new drugs / therapies with short
exposure
• More robust than diagnostic setting– Lesions are bigger more SNR– Longitudinal data self normalizing
BaselineLD0 = 2.7 cmVol0 = 20 cc[tCho]0 = 8.4 mmol/kg
Objective Responder
%ΔtCho24 = -12%, %ΔLD = -44%, %ΔVol = -90%
A
0123456
AC X 1LD24 = 2.7 cmVol24 = 20 cc[tCho]24 = 7.4 mmol/kg
B
0123456
AC X 4LDf = 1.5 cmVolf = 2 cc[tCho]f = 0 mmol/kg
C
0123456ppm
Meisamy et al., Radiology 2004
Objective Responders (N=17/21)
Nonresponders (N=13/15)
Baseline Day 10
1
2
3
4
5
6
7
8
9
[tC
ho
] (
mm
ol/
kg
)
Baseline Day 1
0
1
2
3
4
5
6
7
8
9
[tC
ho
] (
mm
ol/
kg
)
Day-1 ∆[tCho] predicts response:accuracy 83%
PPV 90%NPV 77%
Haddadin et al., NMR Biomed 2009
I-SPY / ACRIN 6657: Multi-site breast MRS trial
• Nola Hylton & Laura Esserman, UCSF
• Monitoring neoadjuvant chemo with DCE-MRI + MRS
• Single voxel MRS, water as internal reference (T2-corrected)
• Stratified by field strength (1.5T/3T) & MR2 timing (1 day / 2-4 days)
• 7 sites accruing, 33% done (March 2009)
Surgery
A/C Taxane
MRI/MRS #1+ 4 cores
MRI/MRS #2MRI/MRS #3
pre-op
UMN1.5T Siemens
UCSF1.5T GE
UC1.5T Philips3T Philips MSKCC
1.5T GE
UPenn3T Siemens
UTSW1.5T Philips3T Philips
UW1.5T GE
3T Philips
Georgetown1.5T Siemens
Mayo1.5T GE
ACRIN 6657 MRS Analysis
MR scanner
databaseSite X
ACRINMRS Lab (UMN)
MRI Lab (UCSF)
TRIAD workstation
analysis
database
analysis
FTP server
PACS
Results
DICOM
Week
Patient 301MR1 MR2 MR3
…
Weekly QC …
Entry QC …
0 1 2 3 4 5 6 7
…
Patient 302MR1 MR2 MR3
…
…
Vegetable oil
40 mm ø sphere w/ 1 mM PCho
20 mm voxel
2 liter bottle
correct incorrectsubcontracted ACRIN CORE Lab
Feedback for training/technical QC
QC Phantom analysis
-400-200020040060080010001200
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
x 104
Open Breast MRS Trials1. Pfizer Phase I, CP-751,871 (Yee)
– anti IGF-1R
– 4T CMRR
2. Novartis Phase II, RAD001/Everolimus (Yee)– mTOR inhibitor
– 4T CMRR
3. Komen, RFA Ablation (Tuttle)– Dual contrast MRI pre- and post-RFA
– 4T CMRR
4. I-SPY/ACRIN 6657 (Peterson/Nelson)– AC/Tax
– Fairview 1.5T / 3T
Methods for High-Field MR: acquisition
x
y
z
Pulse sequences
-500 -500Hz
-300 -100 100 300
TE
(m
s)
45
57
sidebandswater
sidebands
Novel Acquisition Strategies
Novel Hardware
Single-voxelSpectroscopic
imaging
data
residual
baseline
model
Spectral Fitting
Post-processing, artifact correction6 4 2 06 4 2 0
lipidtCho
residualwater
Quantification
1 2
1 2
[tCho]
1
gain T TtCho water
water gain T T tCho
water
tCho water
f f fA
A f f f
MW
0.1 1 10 100
0.1
1
10
0.1 1 10 1000
50
100
Det
ectio
n (%
)[tC
ho] (
mm
ol/k
g)
Voxel Size (mL)
Methods for High-Field MR: analysis
time (s)
A) GRE signal strength B) Simulated Bolus Gd Concentrations
C) Arterial Signal Intensity D) Tissue Signal Intensity
0 1 2 3 4 5 6 7 80
0.05
0.1
0.15
0.2
0.25
[Gd] (mM)S
ign
al in
ten
sity
(a.u
.)
No T2* effect
1.5T blood
3T blood
7T blood
1.5T tissue
3T tissue
7T tissue
0 50 100 150 200 250 3000
1
2
3
4
5
6
7
time (s)
[Gd]
(m
M)
AIF
cancer
normal PZ
time (s)
0 50 100 150 200 250 3000
0.02
0.04
0.06
0.08
0.1
0.12
0.14
0.16
0.18
0.2
Sig
nal i
nten
sity
(a.
u.)
Ignoring T2*
T2* blood @ 7T
0 50 100 150 200 250 3000
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
Sig
nal i
nten
sity
(a.
u.)
Cancer, ignoring T2*
Cancer, w/tissue T2*
Normal PZ, ignoring T2*
Normal PZ, w/tissue T2*
Figure 11 – Simulations showing that R2* effects of Gd-based contrast agents increase at ultra-high field, and substantially impact both blood and tissue signal intensity. See text for details.
Methods for High-Field MR: imaging
Parallel Imaging
Novel Sequences
Simulation, Optimization
7T Body MR from CMRR
Axial
PCho
PCr
Pi
ATP
ProstateWhole-body
MSKLiver
Cardiac