DISCLOSURE Relevant Financial Relationship(s)

1. Medical Advisory Board – GE, Siemens, Hologic, Bayer Medical Inc

2. CEO – Breast-Med Inc, Consulting and Development of Breast Markers

Off Label Usage

University of MN/ CMRR – High Field MRI 4T, 7T, 9.4T – Human Use

8T, 16T – Animal Use

Basic and Advanced MRI Acquisition Techniques BMRI

SBI/ACR Breast Imaging Symposium 2016 Program

Austin Tx April 7-9, 2016

Michael T. Nelson, M.D. Professor of Radiology

University of Minnesota, USA

Learning Objectives

• Breast MRI • Discuss Screening MRI • Diagnostic Breast MRI • New Developments in Breast MRI

– SWIFT – Diffusion – Spectroscopy

University of Minnesota Center for Magnetic Resonance Research

novel devices SWIFT-based MRI scanners

Magnetic Resonance

computer modeling eg, magnetic field calculations

nanoparticle imaging tracking cells

image reconstruction correcting field distortions

novel contrasts T1ρ, T2ρ

8 4 0 -4 -8 -12 -16 -20 -24

spectroscopy cell/tissue viability

pulse sequences

CMRR Research

. . .

G x

G y

G z

ω 1

ω RF

acq

methodology pulse sequences

4 Tesla (Installed in CMRR in ~1990)

Ultra High Field Breast MRI/MRS

Michael T. Nelson, M.D. Patrick J. Bolan, Ph.D.

Center for Magnetic Resonance Research University of Minnesota

3T 4T 7T

Fiber-trajectories of Corpus Callosum

MRI Stewardship in the Era of Personalized Medicine

• MRI is the most significant medical diagnosis discover since x-rays

• The leading diagnostic tool because it images the soft tissues – Anatomically – Biochemically – Functionally

• MRI is noninvasive, safe and doesn’t involve ionizing radiation

• MRI has changed the course of medicine – will it continue to do so in the era of personalized medicine?

1980 1987 Late 90’s

Bilateral breast coil

Gadolinium availability

1986

Pre-gadolinium Post-processing software

2000’s

Consensus on technique Hardware improvements

Dynamic techniques

Late 80’s-Early 90’s

Higher Spatial/temporal

Resolution

Breast MRI Timeline

Implants

breast coils 7-16 channels

Breast MRI/MRS Can Be Used For

• Screening Breast MRI

• Diagnostic Breast MRI

• Response for Neoadjuvant Therapy – Longest diameter of the tumor

– Volume of the tumor

– MR spectroscopy of the tumor measuring metabolites (choline)

Transverse MR image shows volume of interest (36 voxels of 0.25 cm3 each) centered on an invasive ductal carcinoma in left breast of 38-year-old woman.

Dorrius M D et al. Radiology 2011;259:695-703

©2011 by Radiological Society of North America

Transverse MR image shows volume of interest (36 voxels of 0.25 cm3 each) centered on an invasive ductal carcinoma in left breast of 38-year-old woman.

Dorrius M D et al. Radiology 2011;259:695-703

©2011 by Radiological Society of North America

Transverse MR image shows volume of interest (36 voxels of 0.25 cm3 each) centered on an invasive ductal carcinoma in left breast of 38-year-old woman.

Dorrius M D et al. Radiology 2011;259:695-703

©2011 by Radiological Society of North America

Transverse MR image shows volume of interest (36 voxels of 0.25 cm3 each) centered on an invasive ductal carcinoma in left breast of 38-year-old woman.

Dorrius M D et al. Radiology 2011;259:695-703

©2011 by Radiological Society of North America

Multifocal Invasive Ductal Carcinoma Grade 3 (ER-,PR+, Her-2+)

Chemotherapy Response by MRI & MRS 1 wk pre-Tx Day 1

chemo x1 Day 29

chemo x2 Day 50

chemo x3 Day 99

chemo x4

Invasive ductal cancer 5.29 6.40 2.40 1.87 0

2.7cc 3.0cc 1.3cc 0.4cc 0.3cc

Conclusions: Multiparameter

Spiculated mass, with washout, [tCho] = 5.3 mmol/kg, T2 = 47 ms, ADC = 1.5 x10-3 mm2/s

MRS Translational Research Imaging

• ISPY 2 - ACRIN 6657 is the imaging

component of the larger I-SPY neoadjuvant

breast cancer treatment trial (CALGB

150007/150012, ACRIN 6657, CBIIT,

InterSPORE)

Critical Path Initiative I-SPY 2 TRIAL Sponsors:

NCI, FDA, NCICB, NIH Foundation

Accrual: Anticipate 800 patients over 3–4 years Participating Sites: 15–20 across US, possibly Europe and Canada

On Study

MRI MRI MRI Blood

Surgery

Biopsy Blood

MRI Biopsy

Tissue

Taxane +/–New Drug (12 weekly cycles)

AC (4 cycles)

I-SPY 2 Adaptive Trial Outline Phase II Neoadjuvant

I-SPY Biomarker Platforms

Expression Arrays

-2

-1

0

1

2

3

4

5

rela

tive

copy

num

ber (

Log2

)

Genome location

)

1 3 5 7 9 11 13 15 17 19 21 X

1q 20q

1p 17p 19p

CGH

Reverse Phase Tissue Protein Lysate Arrays

Tissue: Core or Surgical

H&E,IHC,FISH

UNC, Penn UNC, UCSF George Mason

UCSF

Id1 proteins autoantibodies

phospho proteins

Serum

• Longest diameter

• Choline Spectroscopy

• Volumetric

Radiologic Studies that Measure Neoadjuvant Chemotherapy Response

Example of Volumetric Tumor Analysis

Pre-surgery 6/29/11 Early treatment 2/14/11 Inter-regimen 4/20/11

I-SPY Therapy Paclitaxel and Trastuzumab for 12 weeks

CONCLUSION

• MRI/MRS is not DEAD

• Absolutely best imaging biomarker

– Longest Diameter

– Volume

– MRS – Choline

• NEED Automated Work Station

Breast MRI with DWI DCIS

Breast MRI DWI Invasive Ductal Carcinoma

T2 W images DWI Image ADC map

(this is an animated gif)

Voxel planning

DCE-MRI

time 0 10 min 20 min 30 min

Gd

acquire pre

MRS

loc T2w DWI

40 min

6 4 2 0 ppm

tCho

[tCho] = 2.0+/-0.9 mmol/kg

MRS for Br Ca Treatment Response

6 4 2 0 ppm

tCho

[tCho] = 2.0 ± 0.9 mmol/kg

lipids

residual water

lipids lipids

A B

0 1 2 3 4 5 6 0 1 2 3 4 5 6 0 1 2 3 4 5 6

Pre-treatment 1 day of chemo 6 weeks of chemo

Multi-band Breast DWI

Standard DWI ADC

MB-DWI ADC

Standard DWI b=0

MB-DWI b=0

0 1 2 3 4 5 6

0

0.01

0.02

0.03

0.04

FT-csi

SLIM full K

SLIM 1/4 K

ppm

-1 0 1 2 3 4 5 6

0

0.5

1

1.5

2

2.5

3

FT-csi

SLIM full K

SLIM 1/4 K

ppm

a) b) c)

d) e)

tCho

water

lipids

Chemotherapy Response by MRI & MRS 1 wk pre-Tx Day 1

chemo x1 Day 29

chemo x2 Day 50

chemo x3 Day 99

chemo x4

Invasive ductal cancer 5.29 6.40 2.40 1.87 0

2.7cc 3.0cc 1.3cc 0.4cc 0.3cc

Pat Bolan – Breast MRI projects

• ISPY2 / ACRIN 6698 – Multisite neadjuvant trial – Tumor volume + genetics – Diffusion imaging

• Breast MRSI

– novel technology developments

– SLIM and PEPSI

• Integrating Cardiac MRI with Breast MRI – w/Suma Konety, Cardiology

On Study

MRI MRI MRI Blood

Surgery

Biopsy Blood

MRI Biopsy

Tissue

Taxane +/–New Drug (12 weekly cycles)

AC (4

cycles)

patrick bolan: bolan@cmrr.umn.edu

0 1 2 3 4 5 ppm

Bolan – Whole-body Bone Marrow

• Quantifying bone marrow composition with water-fat (Dixon) imaging

• Assessing BMT engraftment in leukemia patients

• Developing whole-body marrow metrics

With Susanta Hui, Rad. Onc.

patrick bolan: bolan@cmrr.umn.edu

Pre-Tx 6-month 12-month 100%

0%

100%

0%

wfM

RI

CT

Future of Breast – SWIFT Breast MRI

Michael T. Nelson, M.D. Professor of Radiology

Curt Corum, PhD University of Minnesota, USA

New UMN Technology: SWIFT MRI

Entirely new way of doing MRI • Continuous scanning: quiet, fast, efficient • Can see what regular MRI cannot

– Lung, bone, calcifications • Better for contrast agent imaging • Can be used with smaller, cheaper magnets

SWIFT • SWeep Imaging with Fourier

Transform Simultaneous interleaved excitation

and acquisition 3D Radial Sampling (Halton sequence) PD or T1 weighted Smooth Gradient Update (Quiet)

robust against motion, eddy currents, and system timing

SWIFT Timing

SWIFT has extremely short dead time On the order of 2-6 μs Sensitive to fast relaxing spins Preserves signal from off resonant spins

4 T SWIFT Breast Coils

SWIFT compatible Dual Breast Coil 4 ch Transmit/Receive, 4 T UMN Physics Machine Shop, Peter Ness CMRR Gregor Adriany, Carl Snyder Now in imaging testing

Modified Single Breast Coils 2 ch Transmit/Receive, 4 T CMRR Carl Snyder Helmut Merkle (now at NIH) Currently in use

Case FA

Case mass like DCIS

Case IDC

Ongoing Study...

We have now recruited 24 patients and have 20 successful sessions 3 of the incompletes were due to last minute exclusions one due to scanner failure

SWIFT visualizes lung parenchyma (respiratory gated, mouse @ 9.4 Tesla)

Metastatic Breast Cancer Lesions in Lung

Dental Imaging with SWIFT

enamel

caries

pulp

dentin

cementum

SWIFT MRI X-ray

SWIFT Breast MRI - Examples

Benign Malignant

Dedicated Breast SWIFT magnet

Summary Breast Screening

Equipment Cost of Equipment

Exam Cost Radiation Dose

Digital Mammography

400K $250 Low

With Tomosynthesis

200K $150 High

BSGI 400K $400 High

PEM 1.2M $4000 Very High

Body PET 2M $4000 Very High

MRI 1.5T 2M $1500 None

SWIFT MRI 450K $450 None

• All women (All risks) should have a contrast mammogram or contrast MRI every 2-3 years ! 30m USA 40m Europe 50m Asia 120m 1 year/- 60m every other year

• Are there enough Radiologist and Equipment to do this screening?

UMN CMRR Breast Group Faculty Patrick Bolan, PhD Jutta Ellermann, MD Tim Emory, MD Lenore Everson, MD Michael Garwood, PhD Evin Gulbahce, MD Pierre-Gilles Henry, PhD Michael Nelson, MD Todd Tuttle, MD Tommy Vaughan, PhD Doug Yee, MD

Students/Postdocs/RAs James Boyum, MD Curt Corum, PhD Ihab Haddadin, MD Djaudat Idiyatullin, PhD Isabelle Iltis, PhD Yakir Levin, BS Joseph Lin, PhD Malgorzata Marjanska, PhD Adeka McIntosh, MD Sina Meisamy, MD Shalom Michaeli, PhD Jang-Yeon Park, PhD Nate Powell, BS Carl Snyder, MS Angela Styczynski, BS

Research Supt. Janice Kruse Bibi Husain Lou Forsythe, RN Juliette Gay, RN GCRC Nursing Staff

Biostatistics Chap Le, PhD Robin Bliss, MS Lynn Eberly, PhD

CMRR Director Kamil Ugurbil, PhD

Current Funding National Institutes of Health

Susan G. Komen Foundation

RSNA Research Scholar

Grant (Bolan)

Tickle Family Land Grant Endowment in Breast Cancer

Research (Yee)

Lillian Quist-Joyce Henline Chair in Biomedical Research

(Garwood)

Center for MR Research UMN Medical Center

Clinicians Barbara Bowers Richard Carlson Elena Chiorean Gary Grammens Patricia Judson Tanya Melnik James Roelofs Susan Seatter Amy Spomer Richard Zera many others…