Multi-Modality Imaging

Multi-Modality Imaging:Technologies, Applications, and Future Directions

Multi-Modality Imaging:Technologies, Applications, and Future Directions

Jeff Siewerdsen, PhDOntario Cancer Institute, Princess Margaret Hospital

Department of Medical BiophysicsDepartment of Radiation Oncology

Department of Otolaryngology – Head and Neck SurgeryInstitute of Biomaterials and Biomedical Engineering

University of Toronto

Continuing Education Session MO-B-352

Multi-Modality Imaging• Becoming the standard of clinical care

- Diagnosis and staging- Treatment planning- Response assessment

• Also at the heart of the rapidly evolving field of molecular imaging (genetic expression etc.)

• Primary modalities- Structural / morphological imaging

• CT• MR• Ultrasound

- Functional / molecular imaging• PET• SPECT• Optical• fMRI

Multi-Modality Imaging• A highly inter-disciplinary field of research:

- Clinical oncology, neurology, cardiology,…- Engineering, physics- Biochemistry, pharmacology, nanotechnology- Cell and molecular biology

• Applications throughout clinical and preclinical medicine- Cancer screening, staging, response monitoring- Integrated stroke imaging- Neurological assessment- Drug development- Small animal imaging

µCT, µPET, µSPECT, µMRI, optical (fluorescence, bioluminescence) - Fundamental understanding of disease origin, progression, response

Multi-Modality Imaging• Basic goal:

Spatial co-localization of complementary information(e.g., structure and function)

• Typified by the integration of 2 or more modalities:• CT • MR • Optical• PET • SPECT • other…

… in serial examinations:- successive scans (subject to deformation and temporal change)� Accurate registration is essential.

… or (more recently) within a single, integrated exam:- Multiple modalities incorporated within a hybrid scanner- Double- or triple-labeled reporters (e.g., optical or nuclear agents)� Active areas of technology development.

Ultrasound

On Structure… and Function

CT

MR

“ Structure withoutfunction is a corpse…… function withou structure is a ghost.”

(StephenWainwright) Optical

On Structure… and Function

PET

SPECT

“ Structure withoutfunction is a corpse…… function withou structure is a ghost.”

(Stephen Wainwright)

Morphology Function

MR

CT

SPECT

PET

Optical

Multi-Modality Imaging Serial MMI Examinations• Conventional approach to MMI

Successive image acquisition on separate scanners

• Accurate image registration is criticalAnatomical deformation arising from:

- Variation in patient setup- Anatomical / physiological motion (respiration and cardiac)- Anatomical / physiological change (disease progression)

• Multi-modality image registrationRigid registration:

- All voxels transformed according to a common translation

Deformable registration:- Each voxel transformed ~independently of its neighbors- Approaches include:

• B-spline, TP-spline, Optical flow (Demons), FEM, …- Note: MMI reg can not rely solely on pixel intensities

Serial MMI Examinations

CT+PETFusion

PET

CT

• Serial CT + PET:- Replaced by hybrid PET-CT (~1998)- T. Beyer, DW Townsend, T Brun et al.

J. Nucl. Med. (2000).

• Serial MR + PET:- Neurosurgery planning- Localization of epileptic foci- Stroke (MR perfusion + PET)- Hybrid MR-PET now developed (2007)

• Serial CT + MR:- Radiation therapy planning- Motion modeling- Response assessment- Platform for development in

deformable image registrationC. P. Schultz, PhD

Global Business Development, Siemens Medical Solutions

Serial MMI Examinations• Serial CT + PET:

- Replaced by hybrid PET-CT (~1998)- T. Beyer, DW Townsend, T Brun et al.

J. Nucl. Med. (2000).



deformable image registration

J. Leong, J. Otolaryngol –Head and Neck Surg. (2006)

Serial MMI Examinations• Serial CT + PET:

- Replaced by hybrid PET-CT (~1998)- T. Beyer, DW Townsend, T Brun et al.

J. Nucl. Med. (2000).



deformable image registration

N. CharnleyBrit. Journ. Radiol. 78 (2005)

Deformable Modeling• Integrating multi-

modality and multi-instance images

• Resolving geometric discrepancies between images

• Tracking tissue throughout Tx

≠≠≠≠

= K. K. BrockPrincess Margaret Hospital, Toronto ON

Example: CT-MRCT and MR images acquired in serial

and fused according to (rigid or deformable) image registration…

Integrated (Hybrid) MMIMultiple modalities integrated within a single exam:

- Integrated hardware: hybrid scanners

Active areas of technology development- PET-CT… SPECT-CT- MR-PET… MR-Ultrasound… MR-Optical

Simultaneous (or near-simultaneous) acquisition- Improves accuracy of co-registration / co-localization- Synergy of information (e.g., attenuation correction)- Improves clinical space, time, and workflow requirements

OR

Morphology Function

MR

PET

Optical

Multi-Modality Imaging

SPECT-CT

CT

SPECT

SPECT-CT• Primary advantages

- Attenuation correction- Structural / anatomical referencing

• Early development- First truly integrated hybrid

• UCSF (Hasegawa et al.)• Single-head SPECT + Single-slice CT• Demonstrated potential of SPECT-CT

- First commercially available system• GE Hawkeye (1999)• Dual-head SPECT• Single-slice CT

- 13 s (180o+Fan) rotation- Low-mA (low-dose); low image quality- Exquisite attenuation map(compared to line-source radionuclide)

Sodee et al.Sem. Nuc. Med. 37 (2007)

Hasegawa et al. (1994)

GE Hawkeye (1999)

SPECT-CT

Hawkeye (GE)(Infinia SPECT)

+(Low-power x-ray CT)

Precede nce (Philips )(Skylight SPECT)

+(16-slice CT)

Symbia (Siemens)(Symbia S SPECT)

+(16-slice CT)

SPECT-CT: Attenuation Map• Basic principle

- Estimate heterogeneous attenuation map, µ- Incorporate in iterative SPECT recon (OSEM)

IterativeReconstruction

TransmissionProjection

FBP

TransmissionCT

EmissionProjection

EnergyCalibration

0.00

0.05

0.10

0.15

0.20

Air

60%

ET

OH

Wat

er0.

9%S

alin

e

100

mg/

cc20

0m

g/cc

300

mg/

cc40

0m

g/cc

50m

g/cc

-1000 -800 -600 -400 -200 0 200 400 600

AttenuationMap

Attenuation-corrected

SPECTimage

Images courtesy of B. Hasegawa, UCSF


Uncorrected SPECTCorrected



EmissionProjection

EnergyCalibration

0.00

0.05

0.10

0.15

0.20

Air

60%

ET

OH

Wat

er0.

9%S

alin

e

100

mg/

cc20

0m

g/cc

300

mg/

cc40

0m

g/cc

50m

g/cc

-1000 -800 -600 -400 -200 0 200 400 600

AttenuationMap

Images courtesy of B. Hasegawa, UCSF

X-ray CT

Attenuation Map



Adapted from M. O’Connor and B. Kemp, Sem. Nuc. Med. (2007)

Uncorrected

CT-Corrected

Line-SourceCorrected

SPECT


EmissionProjection

Attenuation Map

ScanningLine-SourceRadionuclide

(Gd153)

CT Scan

OR



• Primary Advantages of CT- (compared to line-source radionuclide Gd153)- Lower noise- Minimal cross-talk from SPECT tracer- Electronic (does not decay)- Faster- (Note: spatial resolution not a key advantage)

• Disadvantages- Sequential (not simultaneous)- Motion can occur- Temporal aperture mismatched to SPECT

• CT: seconds (a snapshot)• SPECT: 15-20 min (average over resp cycle)

• Potential solutions- Slow CT- 4D gated CT (average over resp cycles)- Motion modeling

Uncorrected

CT-Corrected

Line-SourceCorrected

SPECT

SPECT-CT: ApplicationsCT

111In SPECT SPECT-CT

Y. Krausz and O. Israel, Sem. Nuc. Med. (2007)

Precise localization ofa 13 cm tumor mass in the liver…

… and a 2.1 cm primary tumor

LDCT shows noanatomicalabnormalityor fracture…

… SPECT-CTindicates metastasis

SPECT-CT: Detection of Bone MetsBone SPECT-CT

(57-yo M with NSCLC)

Followup MDCT(reveals bony erosion consistent

with soft-tissue tumor metastasis)

Bone SPECT-CT(56-yo M with NSCLC)

M. Horger and R. Bares, Sem. Nuc. Med. (2007)

SPECT-CT: Prostate and Breast

CT

SPECTProstaScint

SPECT-CT

Uptakepredominantto left commoniliac nodes

D. Husarik and H. Steinert, Sem. Nuc. Med. (2007)D. Sodee et al., Sem. Nuc. Med. (2007)

Morphologicalcorrelation oftracer uptaketo a lymph node

SPECT-CT: BrainGlioma(post Surgery+RT)

Focal Tc-99m uptakeindicates viable tumor

Glioblastoma(post Surgery+RT)

MRI suspiciousof residual tumor

SPECT-CTnegative for viable tumor

O. Schillaci et al., Sem. Nuc. Med. (2007)

SPECT-CTCurrent and Future Technical Applications

• SPECT dosimetry- Use CT for more accurate estimation of organ volume- More accurate quantitation of tumor uptake, dose

• One-stop cardiology- Quantify coronary Ca- Evaluate patency of coronary arteries- Assess myocardial perfusion- Will require fast (64-slice) CT capable of imaging coronary arteries

• Detector development- Single detector systems for both SPECT and CT- Simultaneous x-ray and gamma operation (not count-rate limited)- Semiconductor detectors (CdZnTe)

- “Current mode” (x-rays)- “Event mode” (gamma)

• Image registration techniques- Patient motion – still an issue (e.g., chest / abdomen)- MR is sometimes the other modality of choice (e.g., brain)

- MR-SPECT still under development

SPECT-CTSeminars in Nuclear Medicine (Vol. 36, 2007)

- M. O’Connor and B. Kemp (Mayo Clinic)

SPECT-CT: Basic instrumentation and innovations- Y. Krausz and O. Israel (Hadassah)

SPECT-CT: Endocrinology- O. Shillaci (University Tor Vergata, Rome)

SPECT-CT: Lung Cancer and Malignant Melanoma- M Horger and R. Bares (Tubingen)

SPECT-CT: Benign and Malignant Bone Disease- T. Bunyavorich et al. (Boston University)

SPECT-CT: Evaluation of Infection and Inflammation- D. Sodee et al. (Case Western)

SPECT-CT: Prostate Cancer- D. Husarik and H. Steinert (Zurich)

SPECT-CT: Sentinel Node Mapping in Breast Cancer- O. Shillaci et al. (University Tor Vergata, Rome)

SPECT-CT: Brain Tumors- O. Shillaci et al. (University Tor Vergata, Rome)

SPECT-CT: Abdominal Diseases

Morphology Function

Optical


MR-PET

SPECT

MR

PET-CTCT

PET

Simultaneous MR-PET

B Pichler et al., University Hospital, TuebingenD Townsend et al., University Hospital, TennesseeSiemens Medical Solutions

MR PET (FDG) MR-PET

• Original motivation- To improve PET spatial resolution by reducing the range of positron

travel within a magnetic fieldB. E. Hammer et al., “Use of a magnetic field to increase the spatial resolution of positron emission tomography,” Med. Phys. 21 (1994).

• Motivation has shifted to simultaneous image acquistion- Similar acquisition times for MR and PET (~minutes)- Real-time MR (e.g., navigator-based planar imaging) can be used

to rebin the PET data (4D PET)

• Early challenge: MR-compatible PET detectors- A single ring LSO detector within the magnetic field- Coupled to position-sensitive PMTs placed outside the field- Long (3-4 m) fiber optic coupling (Simon Cherry, UCLA)

K. Farahani et al., “Contemporaneous positron emission tomography and MR imaging at 1.5 T,” J. Magn. Reson. Imaging 9 (1999).

MR-PET

• Avalanche photodiodes (APDs) provide an improved MR-compatible PET detector

• Can operate in high magnetic fields

• Still required incorporation of APD control / readout electronics within the magnetic field.

Image adapted from M. Schwaiger et al.Technical University Munich

[email protected]

MR-PET

MR-PET

Adapted from M. Schwaiger et al.Technical University Munich

[email protected]

• PET is acquired with a ring positioned insidethe MR magnet

• Permits simultaneous acquisition of MR and PET images within an identical reference frame

MR-PET: Early Success

B. Pichler, M. Judenhofer, C. Claussen (University of Tubingen, Germany)C. Catana, S. Cherry (University of California, Davis CA)

B. Swann S. Siegel, R. Nutt (Siemens Preclinical Solutions, Knoxville TN)W. Jung (Bruker BioSpin MRI, Ettingen, Germany)

Simultaneously acquired PET and MR of a mouse headPET: [18F]FDG (filtered backprojection)

MR: fast low angle shot, no contrast mediumIncreased uptake in PET localizes to the harderian glands

MR-PET: Preclinical Studies• B Pichler et al. “Performance test of an LSO-

APD detector in a 7-T scanner for simulataneous PET/MRI” J. Nucl. Med. (April 2006)

• R Raylman et al. “Simultaneous MRI and PET imaging of a rat brain” Phys. Med. Biol. (2006)

• Catana et al. “Simultaneous acquisition of multislice PET and MR images: Initial results with a MR-compatible PET scanner” J. Nucl. Med. (December 2006)

• R Raylman et al. “Simultaneous acquistion of MRS and PET with a prototype MR-compatible, small animal PET imager” J. Mag. Res. (2007)

• C Catana et al. “Simultaneous in vivo PET and MR imaging” Proc. Nat. Acad. Sci., PNAS (March 2008)Catana et al. PNAS (March 2008)

MR-PET: From Feasibility to Reality

B. Pichler et al., ISMRM 2007University of Tubingen, Germany

in collaboration with Siemens Medical Solutions

M. Judenhofer et al. “PET-MRI: A new approach for functional and morphological imaging”Nature Medicine (March 2008)

PET

MR

MR-P

ET

Neurology• Alzheimer’s disease… Localization of epileptic foci• Neurosurgery planning and evaluation… Stroke imaging

Oncology• Treatment planning and therapy assessment• Improved visualization of soft-tissue targets and

surrounding normal tissues• Accurate registration of intra-tumor morphology and

function• Structural / biochemical / functional assessment

MR + MRS + PET

Cardiac• Assessment of myocardial blood flow (MBF) improved

- N-13 or O-15 PET flow tracers• Delineation of infarcted tissue

- MR (high resolution) + PET (high specificity)

MR-PET: Applications

Advantages of PET-MRSimultaneous; therefore identical physiological conditionsFaster than sequential scanning; no motionBetter soft-tissue contrast resolutionNo radiation dose (MR), supporting sequential studies, pediatrics, etc.MR can be used with a variety of contrast agents for functional imagingMRS can provide biochemical content matched to metabolism (PET)Increased functionality: MR, fMR, MRS, and PET

MR-PET: Point / Counterpoint

DisadvantagesExpensive

SlowDifficult to derive attenuation coefficents for PET attenuation correction

Diagnostic utility for whole-body imaging not clear

Zaidi Mawlawi

Morphology Function


CT

SPECT

PET

MR-Optical Optical

MR

MR-Optical

M. Allard, et al. (Toronto)J. Biomed. Optics 12(3) (2007)

Combined MR + Bioluminescence

MR+BLIPlatformRF Coil

Gas / AnesthHeating

Transparent Base

MR

segm

ente

d

DorsalView

MeasuredLight Exittance

Exittance(Heterogenous)

- from MR -

Exittance(Homogeneous)

- intestines -

Exittance(Homogeneous)

- muscle -

C. M. Carpenter, B. W. Pogue, et al. (Dartmouth University)Optics Letters 32(8) (2007)

MR-OpticalCombined MR + NIRS Imaging of the Breast

NIR insidebreast coil

MRIT1

DCE

NIR plane

SubtractionPost-injection

Pre-injection

Hemoglobin OxygenSaturation

WaterFraction

ScattererSize

ScattererDensity

Topical ReviewPhysics in Medicine and Biology (Vol. 53(4): 2008)- D. W. Townsend

Multi-Modality Imaging of Structure and Function

Discussion• Multi-modality imaging a central component of current

and future clinical and preclinical medicine- Preclinical: Fundamental nature and response of disease- Clinical: Screening, Dx, staging, Tx planning, response assessment

• Burgeoning area of research:

- Deformable image registration• Key to serial and multi-instance exams

- Technology development and clinical investigation• Hybrid structural / functional imaging in a single scanner• PET-CT • SPECT-CT • Optical-CT• MR-PET • MR-Optical • other…

• Clinical applications• Oncology, Neurology, Cardiac, IG interventions, …

Thank you.Thank you.Thank you.

Neurology• Neurosurgery: Delineation

of eloquent brain pre and post Surgery + RT

• Epilepsy: More accurate localization of epileptic foci.

• Stroke: MR perfusion + PET

• Alzheimer’s: O-15 PET + MR + MR(BOLD)

MR-PET: Applications

FDG-PET + MRI (or BOLD)Precise localization of epileptic foci

Correlation with blood flowEarly assessment of response to therapy

FDG-PET mapped to MR

C. P. Schultz, PhDGlobal Business DevelopmentSiemens Medical Solutions

SPECT-CT: Lung

O. Schillaci, Sem. Nuc. Med. (2007)

Non-Hodgkins Lymphoma(Post-Chemotherapy)

SPECT-CT localizes viable tumorwithin a mediastinal mass

Non-Small Cell Lung Cancer

SPECT-CT shows focal uptakeof Tc-99m (metastatic lymph node)

SPECT-CT: InfectionPneumonia Post-Operative Chest Surgery

(Sternum)

WBC Marrow

Discordant WBC / Marrow SPECT-CTindicates osteomyelitis

T. Bunyavorich et al., Sem. Nuc. Med. (2007)

Documents

Multi-Modality Imaging