MR-Guided Near Infrared SpectralTomography of the Breast

Keith D. Paulsen, PhDThayer School of Engineering, Dartmouth College

Department of Radiology, Dartmouth Medical School

Optical Molecular Interactions

AbsorptionElastic ScatterLuminesce Raman

More features ���� better specificity

Higher probability of interaction

Why Image the Breast with Light?

Major absorbers (chromophores) in breast tissue

Near-Infrared imaging:

1. Non-invasive

2. Non-ionizing

3. Relatively inexpensive

Courtesy of Brian Pogue

Molecular level information:Blood vessel densityLocal Metabolism Cellular size and density

Tissue Targeting:Vascular leakageSelective UptakeReceptor Binding

How to Image whenPhoton scatter affects resolution

values from: Castro et al. XraySpec. 2005

X-Ray Fluence NIR Fluence

1.2cm 1.2cm

Bartrum & Crowe, AJR, 1984

NearNear--Infrared System Infrared System -- 20042004

- 3 planes- 6 wavelengths

Light source

Transmitted light detection

0( ) ( , ) ( ( ) ) ( , ) ( , )a

iD r r r r S r

c

ωω µ ω ω−∇ ∇ Φ + + Φ =r r r r r�

1[ ] ( )T T C MJ J I Jµ λ −∆ = + Φ −Φ

Major absorbers (chromophores) in breast tissue

HbT = HbO2 + Hb

StO2 = HbO2/ HbT

Complex Diffusion equation

Newton-Raphson method

ACR 1 Results Summary

NIR ACR 1 Results

77 Women, 150 Exams

NIR Results Stratified by Size

AUCs: CA-N = 0.88; CA-nCA = 0.82; CA-AB = 0.76

Poplack et. al Radiology 243:350-359,2007

MicroscopeUltrasound

Image-Guided Optical Molecular Spectroscopy

X-ray CT MRI

Optical Spectroscopy

AbsorptionElasticScatter

Luminesce Raman

More features ���� better specificity

Higher probability of interaction

MR-guided Optical Imaging

MR• Spatial maps

• Suspect lesions

Optics• Hemodynamic

content

+

• Tissue types

• Water content

• Blood oxygen (BOLD)

• Quantification

High resolution maps of:HbT, StO2, H2O & Scatter

*Brooksby et al. PNAS (2006).

Patient Interfaces – circular & compression

Carpenter et al, Optics Express (2008)

Optically Coupled Philips 3T MR Coil for Breast Imaging

Top view

Side view

Data Collection

Transmit near infrared light through tissue to determine light absorption

μa

Data Collection

Transmit near infrared light through tissue to determine light absorption

μa

Data Collection

Transmit near infrared light through tissue to determine light absorption

μa

Incorporating MR Spatial ImagesIncorporating spatial data from MR with Mimics ©

3D

2D

BEM Method for IG-NIRSImaging Domain

FEM BEM

Light Propagation in a 3-D Breast Model using BEM

Light Propagation in a 3-D Breast Model using BEM

Monitoring Chemotherapy Using Multiple Imaging Sessions

Four Visits Imaged using IG-NIRS

Breast Clip

Blood Volume Index Decreases by 61% between sessions I and II;

96% between I and III

Srinivasan et al, JMRI Submitted, 2009

3D Overlay on MRI – Patient prior to neoadjuvant chemo

Sagittal T1 MR Gross mastectomyspecimen

DCE MR subject with IDC, prior to chemotherapy. Slight enhancement of 1 main node with 3 satellite lesions, all showing increased hemoglobin.

microMolarHemoglobin

Carpenter et al, Opt. Lett. (2007)

Subject post 1 cycle neoadjuvant chemotherapy

3007 - 2 days after Cycle 2

Carpenter et al, Opt. Exp. (in press, 2008)

Lesion characterization: Case Study • Patient with a benign lesion that enhanced in DCE-MR

Patient 1915 – IDCa (coronal display)

Sagittal T1 MR

Carpenter et al, Opt. Lett. (2007)

Gross mastectomyspecimen

Results in 5 Patients

• Results suggest that this technique exhibits high tumor to background contrast

• Oxygen sat, water, scatter show no consistent trends

Malignant

O2 Sat Water

Sc-Amp Sc-Power

Continuous Wave Experiment

Spectrometer-based system

S. C. Davis, H. Dehghani, J. Wang, S. Jiang, B. W. Pogue and K. D. Paulsen, Opt. Express 15(7), 4066-4082 (2007).

Only the change of transmitted light intensity is recorded with CCD cameras.

Combined Frequency-domain & CW Spectrometer System

PMTdetectors

Amplitude modulated laser diodes (8)

Frequency Domain:PMT-based detection system

Spectroscopy detection:16 Acton Research spectrometers with cooled CCD cameras

Philips 3T MRI

3.5

4.0

4.5

5.0

5.5

Atte

nuat

ion

(OD

)

700 800 900

Wavelength (nm)

MR-coupled spectroscopy system

Gelatin Background( 1% blood )

solution inclusion

Contrast in HbT Contrast in water (~100% in solution)

gelatin inclusion

Contrast in HbTHomogeneous water image

2% blood 1% Intralipid

2% blood

700 – 840nm

700 – 840nm

700 – 900nm

700 – 900nm

• CW measurement from 700nm to 900nm with 12 wavelengths.

,

,

.

1 1 1

2 2 2

1 1 1

1 2

1 2

1

21 2

1 2

1 2

( ) ( ) ( )

( ) ( ) ( )

( ) ( ) ( )

( ) ( ) ( )

( ) ( ) ( )

f f f

c c c

FD FD FDN

FD FD FDN

FD FD FDN

CW CW CWN

N

CW CW CWN

J C J C J C

J C J C J CC

CJ C J C J CC J

J C J C J CC

J C J C J C

λ λ λ

λ λ λ

λ λ λ

λ λ λ

λ λ λ

δδ

δ

δ

= =

L

L

M M O M

LM

L

M M O M

L

1

2

1

f

c

FD

FD

FD

CW

CW

I

I

I

I

I

λ

λ

λ

λ

λ

Φ =

M

M

Combine Frequency domain and Continuous wave data sets for spectral reconstruction

Frequency domain

Continuous waveContinuous wave

Absorption Scattering

Amplitude

Phase

Intensity

Mixed Jacobian Matrix

ln ln

aFD

a

I I

DJ

D

µθ θ

µ

∂ ∂ ∂ ∂ =

∂ ∂ ∂ ∂

ln lnCW

a

I IJ

D µ ∂ ∂= ∂ ∂

Dynamic Contrast MRI imagewith GE Signa Excite1.5-T

Patient 1. Ductal carcinoma in situ and invasive ductal carcinoma

Frequency domain

Frequency domain+

Continuous wave

Dynamic Contrast MRI image

Patient 2. Infiltrating ductal carcinoma

Frequency domain

Frequency domain+

Continuous wave

Breast-sized phantoms with ICG: Shallow object

No spatial priors

Soft spatial priors

Hard spatial priors

1.5:1 3.3:1Contrast 6.6:1

Breast-sized phantoms with ICG: Deep object

No spatial priors

Soft spatial priors

Hard spatial priors

1.5:1 3.3:1Contrast 6.6:1

Layered Phantoms10:1 tumor to outer layer3.3:1 tumor to Layer 2

No spatial priors Soft spatial priors Hard spatial priors

Acknowledgements:

Alumni

FUNDING:PO1CA 80139PO1CA 84203RO1CA109558 RO1CA120386 R33CA100984 RO1CA69544R44CA119486

Graduate Students

Engineering & Med School Colleagues

Tayyaba HasanHarvard Med.

Brian WilsonU. Toronto

VenkatKrishnaswamy

ShudongJiang

SubhaSrinivasan

KimSamkoe

WendyWells

StevePoplack

PeterKaufman

JackHoopes

Zhiqiu Li ColinCarpenter

DaxKepshire Jia Wang

AshleyLaughney

ImranRizvi

HengXu

BenBrooksby

ChaoSheng

TroyMcBride

XinWang

HamidDehghani

DaqingPiao

PhaniYalavarthy

SummerGibbs-Strauss

JosiahGruber

ScottDavis

BinChen

Brian Pogue