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