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 My group: Timo Liimatainen (postdoc), Leighton Warmington (BPhys MS), Avani Chandresekaran (CS MS) Center for MR Research UM Medical Center – Fairview

Areas of Research Breast MR imaging and spectroscopy Evaluating cancer treatment response High-field Body MR Technique 3T 4T 7T

Breast MR Spectroscopy Single-Voxel 1H MRS Contrast-enhanced MRI suppressed water lipids Choline compounds (tCho) lipid invasive ductal carcinoma Frequency (ppm) High [tCho]  cancer (proliferation, cell density, upgragulated transport & kinase activity)

Diagnosing Suspicious Lesions at 4T 10 ROC cutoff = 1.0 mmol/kg sensitivity 72% specificity 83% 8 6 [tCho] (mmol/kg) 4 2 Malignant (n=58) Benign (n=54) Normal (n=5) 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

Objective Responder Baseline LD0 = 2.7 cm Vol0 = 20 cc 1 2 3 4 5 6 Baseline LD0 = 2.7 cm Vol0 = 20 cc [tCho]0 = 8.4 mmol/kg AC X 1 LD24 = 2.7 cm Vol24 = 20 cc [tCho]24 = 7.4 mmol/kg B 1 2 3 4 5 6 AC X 4 LDf = 1.5 cm Volf = 2 cc [tCho]f = 0 mmol/kg C 1 2 3 4 5 6 ppm Patient 284 = 8/4/04 – 8/12/04 – 9/23/04 %ΔtCho24 = -12%, %ΔLD = -44%, %ΔVol = -90% Meisamy et al., Radiology 2004

Objective Responders (N=17/21) Nonresponders (N=13/15) Baseline Day 1 1 2 3 4 5 6 7 8 9 [tCho] (mmol/kg) Baseline Day 1 1 2 3 4 5 6 7 8 9 [tCho] (mmol/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 Taxane Surgery MRI/MRS #2 MRI/MRS #3 pre-op MRI/MRS #1 + 4 cores 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) UMN 1.5T Siemens UC 1.5T Philips 3T Philips UW 1.5T GE 3T Philips MSKCC 1.5T GE UPenn 3T Siemens UCSF 1.5T GE Georgetown 1.5T Siemens UTSW 1.5T Philips 3T Philips Mayo 1.5T GE

ACRIN 6657 MRS Analysis Feedback for training/technical QC subcontracted ACRIN CORE Lab QC Phantom analysis

Open Breast MRS Trials Pfizer Phase I, CP-751,871 (Yee) anti IGF-1R 4T CMRR Novartis Phase II, RAD001/Everolimus (Yee) mTOR inhibitor Komen, RFA Ablation (Tuttle) Dual contrast MRI pre- and post-RFA I-SPY/ACRIN 6657 (Peterson/Nelson) AC/Tax Fairview 1.5T / 3T

Methods for High-Field MR: acquisition x y z Pulse sequences -500 Hz -300 -100 100 300 TE (ms) 45 57 sidebands water Novel Acquisition Strategies Spectroscopic imaging Novel Hardware Single-voxel

Methods for High-Field MR: analysis Post-processing, artifact correction Quantification data residual baseline model Spectral Fitting

Methods for High-Field MR: imaging Novel Sequences Parallel Imaging Simulation, Optimization time (s) A) GRE signal strength B) Simulated Bolus Gd Concentrations C) Arterial Signal Intensity D) Tissue Signal Intensity 1 2 3 4 5 6 7 8 0.05 0.1 0.15 0.2 0.25 [Gd] (mM) Signal intensity (a.u.) No T2* effect 1.5T blood 3T blood 7T blood 1.5T tissue 3T tissue 7T tissue 50 100 150 200 250 300 AIF cancer normal PZ 0.02 0.04 0.06 0.08 0.12 0.14 0.16 0.18 Ignoring T2* T2* blood @ 7T 0.01 0.03 0.07 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.

7T Body MR from CMRR Prostate Cardiac Whole-body Liver MSK Axial PCr PCho PCr Pi ATP