Multi-Modality Imaging
• Becoming the standard of clinical care
Multi-Modality Imaging:
Technologies, Applications, and Future Directions
Jeff Siewerdsen, PhD
Ontario Cancer Institute, Princess Margaret Hospital
Department of Medical Biophysics
Department of Radiation Oncology
Department of Otolaryngology – Head and Neck Surgery
Institute of Biomaterials and Biomedical Engineering
University of Toronto
Continuing Education Session MO-B-352
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
- 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
• Basic goal:
Spatial co-localization of complementary information
(e.g., structure and function)
• Typified by the integration of 2 or more modalities:
• CT
• PET
• MR
• SPECT
• Optical
• 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.
On Structure… and Function
CT
On Structure… and Function
PET
SPECT
MR
“Structure without function is a corpse…
… function withou structure is a ghost.”
(Stephen Wainwright)
“Structure without function is a corpse…
… function withou structure is a ghost.”
(Stephen Wainwright)
Ultrasound
Multi-Modality Imaging
Morphology
Function
Optical
Serial MMI Examinations
• Conventional approach to MMI
Successive image acquisition on separate scanners
SPECT
CT
PET
• Accurate image registration is critical
Anatomical deformation arising from:
- Variation in patient setup
- Anatomical / physiological motion (respiration and cardiac)
- Anatomical / physiological change (disease progression)
• Multi-modality image registration
Rigid registration:
- All voxels transformed according to a common translation
MR
Optical
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
Serial MMI Examinations
• Serial CT + PET:
• Serial CT + PET:
- Replaced by hybrid PET-CT (~1998)
- T. Beyer, DW Townsend, T Brun et al.
J. Nucl. Med. (2000).
CT
• Serial MR + PET:
- Neurosurgery planning
- Localization of epileptic foci
- Stroke (MR perfusion + PET)
- Hybrid MR-PET now developed (2007)
PET
• Serial CT + MR:
- Radiation therapy planning
- Motion modeling
- Response assessment
- Platform for development in
deformable image registration
CT+PET
Fusion
Serial MMI Examinations
• Serial CT + PET:
• 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 registration
C. P. Schultz, PhD
Global Business Development, Siemens Medical Solutions
Example: CT-MR
CT and MR images acquired in serial
and fused according to (rigid or deformable) image registration…
≠
- 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)
- Replaced by hybrid PET-CT (~1998)
- T. Beyer, DW Townsend, T Brun et al.
J. Nucl. Med. (2000).
N. Charnley
Brit. Journ. Radiol. 78 (2005)
• Serial CT + MR:
- Radiation therapy planning
- Motion modeling
- Response assessment
- Platform for development in
deformable image registration
J. Leong, J. Otolaryngol –
Head and Neck Surg. (2006)
=
Deformable Modeling
• Integrating multimodality and multiinstance images
• Resolving geometric
discrepancies
between images
• Tracking tissue
throughout Tx
K. K. Brock
Princess Margaret Hospital, Toronto ON
Integrated (Hybrid) MMI
Multi-Modality Imaging
Multiple modalities integrated within a single exam:
Morphology
Function
- Integrated hardware: hybrid scanners
T
SPEC
-CT
SPECT
CT
OR
PET
Active areas of technology development
- PET-CT… SPECT-CT
- MR-PET… MR-Ultrasound… MR-Optical
MR
Simultaneous (or near-simultaneous) acquisition
Optical
- Improves accuracy of co-registration / co-localization
- Synergy of information (e.g., attenuation correction)
- Improves clinical space, time, and workflow requirements
SPECT-CT
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
Hasegawa et al. (1994)
• 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.
GE Hawkeye
Sem. (1999)
Nuc. Med. 37 (2007)
Hawkeye (GE)
Precedence (Philips)
Symbia (Siemens)
(Infinia SPECT)
+
(Low-power x-ray CT)
(Skylight SPECT)
+
(16-slice CT)
(Symbia S SPECT)
+
(16-slice CT)
SPECT-CT: Attenuation Map
• Basic principle
SPECT-CT: Attenuation Map
• Basic principle
- Estimate heterogeneous attenuation map, µ
- Incorporate in iterative SPECT recon (OSEM)
- Estimate heterogeneous attenuation map, µ
- Incorporate in iterative SPECT recon (OSEM)
Transmission
Projection
Emission
Projection
Emission
Projection
FBP
Transmission
CT
0.10
Air
0.05
0.00
-1000 -800 -600 -400 -200
0
200 400 600
Attenuation
Map
Iterative
Reconstruction
Attenuationcorrected
SPECT
image
60% ETOH
Energy
Calibration
0.15
0.10
0.05
Air
60% ETOH
0.15
0.9% Saline Water
50 mg/cc
100 mg/cc
200 mg/cc
300 mg/cc
400 mg/cc
0.20
0.20
0.9% Saline Water
50 mg/cc
100 mg/cc
200 mg/cc
300 mg/cc
400 mg/cc
X-ray CT
0.00
-1000 -800 -600 -400 -200
0
200 400 600
Energy
Calibration
Attenuation
Map
Iterative
Reconstruction
Attenuation Map
Images courtesy of B. Hasegawa, UCSF
SPECT-CT: Attenuation Map
• Basic principle
OR
- Estimate heterogeneous attenuation map, µ
- Incorporate in iterative SPECT recon (OSEM)
Line-Source
Corrected
Uncorrected
Emission
Projection
Attenuation Map
• 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)
Line-Source
Corrected
Uncorrected
• Disadvantages
CT-Corrected
CT Scan
SPECT-CT: Attenuation Map
• Basic principle
- Estimate heterogeneous attenuation map, µ
- Incorporate in iterative SPECT recon (OSEM)
Scanning
Line-Source
Radionuclide
(Gd153)
Corrected
Uncorrected SPECT
Images courtesy of B. Hasegawa, UCSF
Iterative
Reconstruction
SPECT
Adapted from M. O’Connor and B. Kemp, Sem. Nuc. Med. (2007)
- 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
CT-Corrected
SPECT
SPECT-CT: Applications
CT
SPECT-CT: Detection of Bone Mets
Bone SPECT-CT
(57-yo M with NSCLC)
Bone SPECT-CT
(56-yo M with NSCLC)
Precise localization of
a 13 cm tumor mass in the liver…
LDCT shows no
anatomical
abnormality
or fracture…
… and a 2.1 cm primary tumor
111In
SPECT
SPECT-CT
Y. Krausz and O. Israel, Sem. Nuc. Med. (2007)
SPECT-CT: Prostate and Breast
Followup MDCT
(reveals bony erosion consistent
with soft-tissue tumor metastasis)
Glioblastoma
(post Surgery+RT)
MRI suspicious
of residual tumor
SPECT
ProstaScint
SPECT-CT
M. Horger and R. Bares, Sem. Nuc. Med. (2007)
SPECT-CT: Brain
Glioma
(post Surgery+RT)
CT
… SPECT-CT
indicates metastasis
Uptake
predominant
to left common
iliac nodes
Morphological
correlation of
tracer uptake
to a lymph node
D. Sodee et al., Sem. Nuc. Med. (2007)
D. Husarik and H. Steinert, Sem. Nuc. Med. (2007)
Focal Tc-99m uptake
indicates viable tumor
SPECT-CT
negative for viable tumor
O. Schillaci et al., Sem. Nuc. Med. (2007)
SPECT-CT
Current 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
Multi-Modality Imaging
Morphology
SPECT-CT
Seminars 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
Simultaneous MR-PET
Function
SPECT
CT
PET-CT
ET
MR-P
PET
MR
MR
PET (FDG)
Optical
B Pichler et al., University Hospital, Tuebingen
D Townsend et al., University Hospital, Tennessee
Siemens Medical Solutions
MR-PET
MR-PET
MR-PET
• Original motivation
- To improve PET spatial resolution by reducing the range of positron
travel within a magnetic field
B. 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)
• Avalanche photodiodes (APDs)
provide an improved MRcompatible PET detector
• Can operate in high magnetic fields
• Still required incorporation of APD
control / readout electronics within
the magnetic field.
K. Farahani et al., “Contemporaneous positron emission tomography and MR
imaging at 1.5 T,” J. Magn. Reson. Imaging 9 (1999).
Image adapted from M. Schwaiger et al.
Technical University Munich
S.Ziegler@lrz.tum.de
MR-PET
MR-PET: Early Success
• PET is acquired with a
ring positioned inside
the MR magnet
• Permits simultaneous
acquisition of MR and
PET images within an
identical reference frame
Simultaneously acquired PET and MR of a mouse head
PET: [18F]FDG (filtered backprojection)
MR: fast low angle shot, no contrast medium
Increased uptake in PET localizes to the harderian glands
Adapted from M. Schwaiger et al.
Technical University Munich
S.Ziegler@lrz.tum.de
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)
• B Pichler et al. “Performance test of an LSOAPD detector in a 7-T scanner for
simulataneous PET/MRI” J. Nucl. Med. (April
2006)
MR-PET: From Feasibility to Reality
PET
MR-PET: Preclinical Studies
M. Judenhofer et al. “PET-MRI: A new approach
for functional and morphological imaging”
Nature Medicine (March 2008)
• R Raylman et al. “Simultaneous acquistion of
MRS and PET with a prototype MRcompatible, small animal PET imager” J. Mag.
Res. (2007)
Catana et al. PNAS (March 2008)
• C Catana et al. “Simultaneous in vivo PET and
MR imaging” Proc. Nat. Acad. Sci., PNAS
(March 2008)
MR-PET: Applications
MR-PET
• Catana et al. “Simultaneous acquisition of
multislice PET and MR images: Initial results
with a MR-compatible PET scanner” J. Nucl.
Med. (December 2006)
MR
• R Raylman et al. “Simultaneous MRI and PET
imaging of a rat brain” Phys. Med. Biol.
(2006)
B. Pichler et al., ISMRM 2007
University of Tubingen, Germany
in collaboration with Siemens Medical Solutions
MR-PET: Point / Counterpoint
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)
Zaidi
Mawlawi
Advantages of PET-MR
Simultaneous; therefore identical physiological conditions
Faster than sequential scanning; no motion
Better soft-tissue contrast resolution
No radiation dose (MR), supporting sequential studies, pediatrics, etc.
MR can be used with a variety of contrast agents for functional imaging
MRS can provide biochemical content matched to metabolism (PET)
Increased functionality: MR, fMR, MRS, and PET
Disadvantages
Expensive
Slow
Difficult to derive attenuation coefficents for PET attenuation correction
Diagnostic utility for whole-body imaging not clear
MR-Optical
Multi-Modality Imaging
Morphology
Combined MR + Bioluminescence
Function
SPECT
MR+BLI
Platform
RF Coil
Gas / Anesth
Heating
Transparent Base
Measured
Light Exittance
Exittance
(Heterogenous)
- from MR -
Exittance
(Homogeneous)
- intestines -
Exittance
(Homogeneous)
- muscle -
CT
MR
segmented
PET
MR
MR-Op
tical
Optical
Dorsal
View
M. Allard, et al. (Toronto)
J. Biomed. Optics 12(3) (2007)
MR-Optical
Combined MR + NIRS Imaging of the Breast
Topical Review
Physics in Medicine and Biology (Vol. 53(4): 2008)
- D. W. Townsend
Multi-Modality Imaging of Structure and Function
NIR inside
breast coil
Pre-injection
Subtraction
Post-injection
NIR
plan
e
MRI
T1
DCE
Hemoglobin
Oxygen
Saturation
Water
Fraction
Scatterer
Size
Scatterer
Density
C. M. Carpenter, B. W. Pogue, et al. (Dartmouth University)
Optics Letters 32(8) (2007)
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
Thank you.
- Technology development and clinical investigation
• Hybrid structural / functional imaging in a single scanner
• PET-CT
• MR-PET
• SPECT-CT
• MR-Optical
• Optical-CT
• other…
• Clinical applications
• Oncology, Neurology, Cardiac, IG interventions, …
MR-PET: Applications
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)
C. P. Schultz, PhD
Global Business Development
Siemens Medical Solutions
FDG-PET + MRI (or BOLD)
Precise localization of epileptic foci
Correlation with blood flow
Early assessment of response to therapy
FDG-PET mapped to MR
SPECT-CT: Lung
Non-Hodgkins Lymphoma
(Post-Chemotherapy)
Non-Small Cell Lung Cancer
SPECT-CT: Infection
Pneumonia
Post-Operative Chest Surgery
(Sternum)
WBC
SPECT-CT localizes viable tumor
within a mediastinal mass
SPECT-CT shows focal uptake
of Tc-99m (metastatic lymph node)
O. Schillaci, Sem. Nuc. Med. (2007)
Marrow
Discordant WBC / Marrow SPECT-CT
indicates osteomyelitis
T. Bunyavorich et al., Sem. Nuc. Med. (2007)