Quantification of 3-D PET/CT Imaging
Janet R. Saffer1,2, Joshua S. Scheuermann1,2,
Joel S. Karp1,2, Amy Perkins3
1. Department of Radiology, University of Pennsylvania
2. PET Core Lab, American College of Radiology
Imaging Network (ACRIN)
3. Philips Medical Systems
Role of PET/CT Imaging
• In oncology, imaging studies playing an
increasingly important role in assessing patient’s
response to treatment
– Serial CT scans are evaluated for changes in number and
size of tumors
– Serial PET scans are assessed for changes in metabolic
activity of the lesions
• Advent of combined PET/CT systems streamlines
the fusion of these anatomic and functional images
AAPM CE: Multimodality Imaging II
Head and neck cancer
July 29, 2008
SNM Image of the Year 1999
Quantification in 3-D PET/CT Imaging
July 29, 2008
Confounding effects
CT: 160 mAs; 130 kVp ; pitch 1.6; 5 mm slices
PET: 7 mCi FDG; 2 x 15 min; 3.4 mm slices
Transverse
• Trying to glean information about patient’s disease state
from quantitative measurements of image data = using
PET as an in vivo biomarker.
• However, there are many confounding effects that
complicate quantification in PET/CT imaging.
• Sources of variability can be grouped into three categories:
– Patient-related
– Instrument-related
– Operator-related
Sagittal
PET/CT scanner
University of Pittsburgh Medical Center
Image courtesy of Paul Kinahan
Quantification in 3-D PET/CT Imaging
July 29, 2008
1
Patient-related factors affecting quantification
The heavy patient problem
Factors we can’t control:
body habitus (affects attenuation and scatter)
patient’s flexibility (ability to hold arms over head)
patient’s ability to hold still (pain, cognitive impairment)
patient’s individual physiology (affects tracer distribution
within patient)
x for FDG imaging, blood glucose level (4 to 6 hr fast)
x
x
x
x
<=200 mg/dL or re-schedule (other thresholds 180 or even 150)
Slim 58 kg
Object
diameter
20 cm
Quantification in 3-D PET/CT Imaging
July 29, 2008
Patient-related factors affecting quantification
“Normal” 89 kg
Relative
attenuation
Peak NEC ratio
Heavy 127 kg
Peak NEC density
ratio
41 kg
1
6
18
27 cm
71 kg
2.2
2.7
4.5
35 cm
106 kg
4.3
1
1
Can’t compensate simply by increasing scan time!
More patient-related factors
Factors we CAN control:
Factors we can’t control:
body habitus (affects attenuation and scatter)
patient’s flexibility (ability to hold arms over head)
patient’s ability to hold still (pain, cognitive impairment)
patient’s individual physiology (affects tracer distribution
within patient)
x for FDG imaging, blood glucose level (4 to 6 hr fast)
x
x
x
x
<=200 mg/dL or re-schedule (other thresholds 180 or even 150)
Quantification in 3-D PET/CT Imaging
Equivalent
pt. wt.
July 29, 2008
• dose administered
– weight-based or does one dose fit all?
– what about CT dose -- adjust mAs of attenuation-correction CT?
• imaging time per bed position
• for FDG, uptake time before imaging
– standardization, e.g. 50-70 minute window, then +/- 5 minutes of that
on return visit
– coping with unusual delays – match on return visit? (at UPenn if
previous scan was positive, we match whatever that previous uptake
time was +/- 5 minutes)
Quantification in 3-D PET/CT Imaging
July 29, 2008
2
Dependence of Standardized Uptake Value (SUV)
on FDG uptake time
Instrument-related factors affecting quantification
x spatial and energy resolution
– partial volume effect
– discriminate against scattered events
x sensitivity: higher sensitivity => lower Poisson noise
x data acquisition mode for PET (2-D vs 3-D)
– 2-D reduces scatter and randoms but at cost of sensitivity
Slim 58 kg
“Normal” 89 kg
Heavy 127 kg
Reference: Lowe VJ, Delong DM, Hoffman JM, Coleman RE. Optimum scanning protocol
for FDG-PET evaluation of pulmonary malignancy. J Nucl Med (1995);36:883-87.
The increase in SUVs with increasing uptake time motivates:
1) Some sites using 90-minute uptake periods instead of 60 (higher tumor to
background contrast and flatter part of curve).
2) Sites performing second timepoint images of lesions to see by how much the
SUV has changed (establishing slope of increase).
Measured AC: Rotating rod/point source
x attenuation compensation method
– using measured AC (MAC) vs. CTAC
Quantification in 3-D PET/CT Imaging
July 29, 2008
Switch to CTAC has effect on quantification
• “…CT-based attenuation correction produced radioactivity
concentration values significantly higher than the
germanium-based corrected values. These effects,
especially in radiodense tissues, should be noted when
using and comparing quantitative PET analyses from PET
and PET/CT systems.”
Transmission
Source
Point or rod source:
Ge-68, Cs-137
Nakamoto Y, Osman M, Cohade C, Marshall LT, Links JM, Kohlmyer S, Wahl RL.
PET/CT: comparison of quantitative tracer uptake between germanium and CT
transmission attenuation-corrected images. J Nucl Med (2002);43(9):1137-43.
• Source rotates around patient
• Ratio of Transmission to Blank scans gives
correction factors:
T/B=exp(-µd)
Quantification in 3-D PET/CT Imaging
July 29, 2008
Quantification in 3-D PET/CT Imaging
July 29, 2008
3
Issues with CT-based attenuation correction
Instrument-related factors continued
• scatter correction method
CT beam hardening
Respiratory motion
– background subtraction method
– single-scatter simulation (model-based)
• additional instrument capabilities
–
–
–
–
respiratory/cardiac gating
motion correction
partial volume correction
Time of Flight (TOF)
CT contrast media
CT truncated FOV
Slide courtesy of Paul Kinahan
Comparison of TOF and nonTOF images: heavy patient
56 year old male with a history of NHL
237 lbs, 37.2 BMI , 15 mCi FDG, 1 hr post-injection
TOF lesion uptake to nonTOF = 1.6
Quantification in 3-D PET/CT Imaging
July 29, 2008
Operator-related factors affecting quantification
• acquisition and reconstruction protocols
– arms up/down, imaging time per bed position
– reconstruction protocol can make a difference in SUVs
• Westerterp, M et al. Quantification of FDG PET studies using standardized uptake
values in multicentre trials: effects of image reconstruction, resolution and ROI
definition parameters, Eur J Nucl Med Mol Imaging (2007) 34:392-404.
1.7cm
Standard clinical TOF protocol Retrospective nonTOF protocol
p202s4
Same patient data reconstructed differently.
A. Perkins et al, “Clinical optimization of the acquisition time of FDG time-of-flight PET”, SNM 2007.
• instrument quality control
– daily QC: air cal, evaluate scan of CT phantom, full PET
system initialization, baseline collection, PMT gain cal,
emission sinogram, check of energy resolution, timing
resolution
• instrument calibrations
– normalization, SUV cal, timing cal
• slow drifts over time characteristic of PMT-based systems
Quantification in 3-D PET/CT Imaging
July 29, 2008
4
Operator-related factors continued
• method of image analysis - How to characterize patient’s disease?
– What to measure? How to measure?
• size of lesion? (2-D or 3-D)?
• max SUV? average SUV within a region of particular size?
– Vendor-specific SUVs due to limitation in current PET DICOM standard
• non-uniform uptake within tumor (e.g. necrotic center)
– Important if using image for treatment planning
– CT not as helpful in determining size of PET lesion as you might think
– image interpretation
– Setting a semi-quantitative threshold for malignancy is difficult (e.g.
SUV =>2.5)
– Image display/analysis tools not optimized for measurement of change
over time
– Intra- and Inter-Reader variability
– Need “harmonization” of interpretation (Juweid et al, 2007)
Quantification in 3-D PET/CT Imaging
July 29, 2008
Slim 58 kg
Heavy 127 kg
From talk by Larry Clark of NIH’s CIP at RSNA 2006 “Imaging as a Biomarker: Importance of Technique.”
Operator-related factors continued
Future Challenges
• method of image analysis - How to characterize patient’s disease?
– What to measure? How to measure?
• size of lesion? (2-D or 3-D)?
• max SUV? average SUV within a region?
– Vendor-specific SUVs -- limitations in current DICOM standard
• non-uniform uptake within tumor (e.g. necrotic center)
– Important if using image for treatment planning
– CT not as helpful in determining size of PET lesion as you might think
• image interpretation
– Setting a semi-quantitative threshold for malignancy is difficult (e.g.
SUV =>2.5)
– Image display/analysis tools not optimized for measurement of change
over time
– Intra- and Inter-Reader variability
– Need “harmonization” of interpretation (Juweid et al, 2007)
Quantification in 3-D PET/CT Imaging
“Normal” 89 kg
July 29, 2008
• Increasing pressure for earlier feedback on treatment efficacy
• Expansion from diagnosis/staging to individualized treatment
• New tracers that reveal how fast a tumor is growing (FLT), how much
oxygen it is using (FMISO, EF-5), whether it is resistant to drugs (FES),
and how much blood supply it has (by tracing angiogenesis). Also markers
for amyloid plaques (PIB, AV-45), apoptosis (Annexin V), phospholipid
precursors to track lipid synthesis (choline analogs).
• Desire for fusion with additional modalities: MR, US, optical
Quantification in 3-D PET/CT Imaging
July 29, 2008
5
Take Home Messages
1)
2)
Reduce variability in factors you can control by standardizing everything as
much as possible
Ensure consistency by creating Standard Operating Procedures (SOPs)
–
–
3)
4)
5)
Complexities inherent in multicenter trials
ACRIN PET SOPs online: http://www.acrin.org
Shankar et al, Consensus Recommendations for the Use of 18F-FDG PET as an
Indicator of Therapeutic Response in NCI Trials. J Nucl Med (2006);47(6):10591006.
If make changes in acquisition and processing protocols, characterize the
effect on quantification and communicate info to clinicians
Clearly label images to denote any differences in acquisition and/or
processing
Communication is vital: between technologist and reader of study, also with
referring physicians, other sections within Radiology and other departments
within your institution.
Quantification in 3-D PET/CT Imaging
July 29, 2008
• Tension between local protocol and desire for uniformity
across sites
– How to handle non-standard acquisition/processing: uptake time,
use of contrast, respiratory/cardiac gating, motion correction,
partial volume correction, time of flight
• Multiple readers
–
Core lab “over”-reads
• Multiple analysis tools
– Makes it difficult to specify a uniform measurement that all
participants can accomplish
– RIDER initiative (Reference Image Database to Evaluate
Response)
• Standardized, open-source tools
Quantification in 3-D PET/CT Imaging
July 29, 2008
Additional complexities in multicenter trials
• Multiple instruments: Difference in performance characteristics
(resolution, sensitivity, scatter fraction, count rate performance)
• Westerterp et al (2007): “Small unavoidable differences in methodology can be
accommodated by performing a phantom study to assess inter-institute correction
factors.”
– ACRIN PET credentialing program - uniform cylinder
• 11% failure rate from faulty SUV and normalization calibrations
– ADNI - 2 acquisition of 3D Hoffman Brain Phantom
– SNM Validation Phantom exercise
• NEMA NU-2 Image Quality (IEC) phantom (without lung insert) made of
Ge-68
– AAPM Task Group 145
• ACR phantom with Ge-68 in 4 of the cylinders in the lid
• Sent to 9 Pediatric Brain Tumor Consortium sites
Data from cylinders submitted to ACRIN for PET credentialing. Indicates that
can’t assume interchangeability of quantification even between cameras of
same make and model.
– The Netherlands protocol
• Presented at June 2008 SNM, paper in print
Quantification in 3-D PET/CT Imaging
July 29, 2008
6
The Netherlands Protocol
•
•
AAPM Task Groups on Related Topics
Protocol for standardization of quantitative FDG whole body PET
studies
Based on standardization of:
1.
2.
3.
4.
5.
patient preparation
matching of scan statistics by prescribing dosage as function of patient
weight, scan time per bed position, percentage of bed overlap and image
acquisition mode (2D or 3D)
matching of image resolution by prescribing reconstruction settings for
each type of scanner
matching of data analysis procedure by defining volume of interest
methods and SUV calculations
a multi-center QC procedure using a 20 cm diameter phantom for
verification of scanner calibration and the NEMA NU 2 2001 Image
Quality phantom for verification of activity concentration recoveries
(i.e. verification of image resolution and reconstruction convergence).
• AAPM Task Group 126 – “PET/CT Acceptance Testing and Quality
Assurance”, Chair: Osama Mawlawi (MD Anderson Cancer Ctr).
• AAPM Task Group 145 - “Quantitative Imaging Initiative: Quantitative
PET/CT Imaging Joint AAPM/SNM Committee”, Chair: Paul Kinahan
(U Wash). Goal: to develop procedures and tools that allow proper
pooling of results from multicenter trials to achieve/increase statistical
and clinical significance.
• AAPM Task Group 174 - “Utilization of 18F-Fluorodeoxyglucose
Positron Emission Tomography (FDG-PET) in Radiation Therapy”,
Chair: Shiva Das (Duke). Goal: to recommend guidelines/protocols for
consistent imaging, consistent treatment planning and consistent
treatment assessment using FDG-PET in radiotherapy.
Boellaard R, Oyen W, Hoekstra C, et al. The Netherlands protocol for standardization of FDG whole
body PET studies in multi-center trials (NEDPAS), J Nucl Med (2008); 49 (Supplement 1):106P.
Quantification in 3-D PET/CT Imaging
July 29, 2008
Quantification in 3-D PET/CT Imaging
Acknowledgements
July 29, 2008
References (in chronological order)
1)
ACRIN PET Core Lab Key Personnel:
• PET/Nuclear Medicine Steering Committee
Chair/Medical Director: Barry Siegel, MD,
Washington University
• Technical Supervisor: Anthony Levering, RT
2)
3)
4)
5)
6)
7)
Lowe VJ, Delong DM, Hoffman JM, Coleman RE. Optimum scanning protocol for
FDG-PET evaluation of pulmonary malignancy. J Nucl Med (1995); 36:883-87.
Young H, Baum R, Cremerius U, et al. Measurement of clinical and subclinical tumour
response using [18F]-fluorodeoxyglucose and Positron Emission Tomography: review
and 1999 EORTC recommendations. Eur J Cancer (1999); 35(13):1773-1782.
Therasse P, Arbuck SG, Eisenhauer EA, et al. New Guidelines to Evaluate Response to
Treatment in Solid Tumors. J NCI (2000); 92(3):205-216.
Nakamoto Y, Osman M, Cohade C, Marshall LT, Links JM, Kohlmyer S, Wahl RL.
PET/CT: comparison of quantitative tracer uptake between germanium and CT
transmission attenuation-corrected images. J Nucl Med (2002); 43(9):1137-43.
Weber WA. Use of PET for monitoring cancer therapy and for predicting outcome.
J Nucl Med (2005); 46(6):983-995.
Coleman RE, Delbeke D, Guiberteau MJ, et al. Concurrent PET/CT with an integrated
imaging system: Intersociety dialogue from the joint working group of the American
College of Radiology, the Society of Nuclear Medicine, and the Society of Computed
Body Tomography and Magnetic Resonance. J Nucl Med (2005); 46(7):1225-1239.
Delbeke D, Coleman RE, Guiberteau MJ, et al. Procedure guideline for tumor imaging
with 18F-FDG PET/CT 1.0, J Nucl Med (2006); 47(5):885-95.
Page 1 of 2
Quantification in 3-D PET/CT Imaging
July 29, 2008
Quantification in 3-D PET/CT Imaging
July 29, 2008
7
References (cont’d)
8)
9)
10)
11)
12)
13)
Shankar LK, Hoffman JM, Bacharach S, Graham MM, Karp JS, Lammertsma AA,
Larson S, Mankoff DA, Siegel BA, Van den Abbeele A, Yap J, Sullivan D.
Consensus Recommendations for the Use of 18F-FDG PET as an Indicator of
Therapeutic Response in NCI Trials. J Nucl Med (2006); 47(6):1059-1006.
Westerterp M, Pruim J, Oyen W, et al. Quantification of FDG PET studies using
standardized uptake values in multicentre trials: effects of image reconstruction,
resolution and ROI definition parameters. Eur J Nucl Med Mol Imaging (2007);
34(3):392-404.
Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography
for response assessment of lymphoma: consensus of the Imaging Subcommittee of
International Harmonization Project in Lymphoma. J Clin Oncol (2007); 25(5):571578.
International Atomic Energy Agency (IAEA) Report: “Quality Assurance for PET
and PET/CT Systems”, 2008. [Poster: SU-GG-I-74] http://www.iaea.org
Boellaard R, Oyen W, Hoekstra C et al. The Netherlands Protocol for Standardisation
and Quantification of FDG Whole Body PET Studies in Multi-Centre Trials. Eur J
Nucl Med Mol Imaging (in press).
Scheuermann J, Saffer JR, Karp JS et al. Qualification of PET Scanners for Use in
Multi-Center Cancer Clinical Trials: The American College of Radiology Imaging
Network Experience (submitting to JNM).
Quantification in 3-D PET/CT Imaging
July 29, 2008
8