The EARL FDG-PET/CT Accreditation Programme & Guideline Developments:
Results of more than 65 Successfully Accredited Sites and Future Perspectives
Disclosure statement
Research support:
Philips Healthcare & Roche
Biomarkers
• Biomarkers are physical entities or images of these entities that
can be measured and used to indicate a biological process,
disease process, or drug response
• A surrogate endpoint, or ‘marker,’ is a laboratory measurement
or physical sign used in therapeutic trials as a substitute for a
clinically meaningful endpoint that is a direct measure of how a
patient feels, functions, or survives, and is expected to predict
the effect of the therapy
Courtesy of Arturo Chiti
Diagnosis
and
staging
Biological
Characterization
TherapyResponse
Evaluation
Restaging
Molecular Imaging with (Q)PET (with CT and/or MR)
Different radiopharmaceuticals to image different metabolic pathways
Courtesy of Arturo Chiti
Standardised Uptake Value
][/][
]/[
kgweightMBqDose
mlkBqcSUV t
TBW =
SUV ‘is’ activity concentration ratio
Weight is sometimes replaced by BSA, LBM, BMI…
Use of SUV in response assessment studies
Absolute SUV:
-Patient eligibility
-Patient stratification
-Lesion selection (PERCIST)
-Residual SUV
Relative of % SUV changes
-% change of the same lesions (EORTC)
-% change of the (5) hottest lesions per scan
+ ∆SUV=0.9 (PERCIST)
For all applications absolute SUV and SUV changes are used
Entire chain of process determines quantitative
result of an imaging biomaker
Picture taken from QIBA FDG PET/CT profile (draft)
Basic principle is same for most (PET
based) imaging biomarkers
Standardisation/harmonization implies:
1. Guidelines or imaging procedures to address user/observer related factors
(uptake time, patient preparation, data analysis/intepretation)
2. Requirements for image data acquisition
(activity, scan acquisition parameters, reconstruction settings)
3. Rules for image/data analysis
4. Criteria for data (e.g. response) intepretation
(1) (2) (3) (4)
PET imaging / SUV uncertainties
Technical factors
– Relative calibration between PET scanner and dose calibrator (10%)
– Residual activity in syringe (5%)
– Incorrect synchronisation of clocks (10%)
– Injection vs calibration time (10%)
– Quality of administration (50%)
Physics related factors
– Scan acquisition parameters (15%)
– Image reconstruction parameters (30%)
– Use of contrast agents (15%)
– ROI (50%)
Biological factors
– Uptake period (15%)
– Patient motion and breathing (30%)
– Blood glucose levels (15%)
R. Boellaard 2009, J Nucl Med Supplement Issue 50: 11S
Glu 200 mg% Glu 79 mg%Karoline Spaepen-Sigrid Stroobants
Department of Nuclear Medicine
University Hospital Gasthuisberg
Leuven, Belgium
Lowe VJ et al. Optimum scanning protocol?for FDG-PET evaluation of pulmonary
malignancy. J Nucl Med. 1995, image taken from Shankar et al. JNM 2006
Effects of different number of OSEM iterations, as seen in the Netherlands, on SUV
SUVmax = 4.0 5.9 6.4 8.6
SUV 50%= 3.0 4.1 4.6 5.9
Entire chain of process determines quantitative
result of an imaging biomaker
Needs consistency
of the execution of
imaging procedure in
longitudinal setting
Standardisation and quantification
• Personalized management of cancer allows the use of specific
drugs
• Molecular imaging techniques can be used to study several
tumors
• FDG PET-CT has been proposed as a surrogate biomarker for
monitoring cancer therapies
• There are several radiopharmaceuticals other than FDG, with the
potential to characterize tumors and monitor response to therapy
• Imaging biomarkers must be standard and quantitative
Courtesy of Arturo Chiti
Quantitative imaging biomarker
Requirements for (quantitative) imaging biomarkers:
• Repeatability (in one patient using the same PET/CT system)
• Reproducibility (between patients, systems and institutions)
of performance, analysis and interpretation
This implies that standardisation & harmonisation of imaging
procedures are essential
FDG PET and PET/CT: EANM Procedure
Guidelines for Tumour PET Imaging:
version 1.0
Eur.J.Nucl.Med.Mol.Imag. 2010
The EANM guideline for FDG PET and PET/CT
provides recommendations for:
• Minimising physiological or biological effects by patient preparation guidelines
• Procedures to ensure accurate FDG administration
• Matching of PET study statistics (‘image quality’) by prescribing FDG dosage as
function of patient weight, type of scanner, acquisition mode and scan duration
• Matching of image resolution by specifying image reconstruction settings and
providing activity concentration recovery coefficients specifications (QC
experiment)
• Standardisation of data analysis by prescribing region of interest strategies and
SUV measures
• Multi-center QC/QA procedures for PET and PET/CT scanners
Multi-center QC and calibration
• Daily QC conform standard procedure of system /
manufacturer
• Calibration QC using (cylindrical) phantom (15-30cm
diameter)
• “Adjusted” NEMA NU 2-2001 Image Quality
procedure/measurement to measure recovery coefficients
as function of sphere size (= ‘effective image resolution’)
• CT-QC cf recommendations of ESR/national law
• Misc. QC (e.g. for scales, alignment etc)
• Calibration QC specification:
• maximum allowable calibration deviation = + or – 10%
(global)
• SUV recovery specifications:
• for SUVmax (focus –as SUVmax is used clinically!)
• for SUVmean
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VOI A50%, new limits
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VOI A50%, new limits
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Multi-center QC and calibration
Multi-center harmonization of quantification
Comparable calibration accuracy and SUV recovery among sites and vendors is
feasible (n=>65)
0.70
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0.90
1.00
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GE
Philips
Siemens
~5% outside specs
Results at first testM Maccredited sites
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GE
Philips
Siemens
GE
Philips
Siemens
Calibration QC – PET/CT and DC
Multi-center harmonization of quantification
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Comparable SUV recovery among sites and vendors is feasible (n=>65)
Image Quality % SUV recovery
Results at first testM Maccredited sites
SUV Max RC - all vendors
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SUV MAX RC - all vendors
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Multi-center harmonization of quantification
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Image Quality % SUV recovery
SUV MAX
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GE
Philips
Siemens
Small differences in RC curve shape between vendors
Most accurate
PSF + SUVmean
(VOI=3D-50%)
Most accurate
No PSF + SUVmax
Lasnon et al. EJNMMI 2013
Should we use PSF reconstructions?
Note that simple SUVmean & 3D
50% VOIs only perform well:
- Simple phantoms
- No tracer uptake heterogeneity
- Good scan statistics
None of these characteristics
are met in clinical practice.
(Cheebsumon et al. JNM 2011,
EJNMMI 2011)
Why do we use SUVmax?
SUVmax suffers from
upward bias due to noise (Boellaard et al, JNM 1996, 2011, Lodge et al, JNM 2011)
poor reproducibility and accuracy for PSF (HD) reconstructions
(Tong, IEEE TNS 2011, Rahmim et al. MedPhys 2013, Lasnon et al. EJNMMI 2013)
Despite these limitions:
• May represent metabolically most active part of tumor
• VOIs are not standardized – simple isocontour work only well for simple phantoms
• CT and PET based manual segmentation suffer from observer variability
• CT based segmentation may suffer from CT-PET alignment issues
• PET based automated delineation methods:
• variability of methods
• variability in implementation of same method
• performance depend strongly on underlying image characteristics
(Cheebsumon et al. JNM2011, EJNMMI 2011)
• cannot deal well with tracer uptake heterogeneity
•Therefore, need to optimize image quality for use of SUVmax
Future directions
SUVmax suffers from:
upward bias due to noise
(Boellaard et al, JNM 1996, 2011, Lodge et al, JNM 2011, Lasnon EJNMMI 2013)
poor reproducibility and accuracy for PSF (HD) reconstruction
(Boellaard et al., JNM 2011, Tong, IEEE TNS 2011, Lasnon et al. JNM 2013)
1. Explore use of SUVpeak:
• 1ml spherical VOI located at highest average value
• good surrogate for SUVmax
• almost no observer variability
• less sensitive to scanner performance differences
• BUT, no everywhere available – inventory among accredited sites is ongoing (Q4/2013)
2. Explore implementation of EARL compliant acq/recon protocols by vendors
• Positive feedback from and ongoing discussions with GE, Philips and Siemens
• Explore strategy proposed by Lasnon et al. EJNMMI 2013
• 2nd recon or post-recon filter after PSF recon
3. Include measure and upper limit for noise within the IQ-QC experiments
Future directions
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SUV MAX SUV PEAK
SUV RC for 2 different PET/CT systems:
• more difference in SUV MAX RC between systems than with PEAK
• SUV PEAK RC more ‘smooth’ curve, less sensitive to image artefacts
(next slide)
Makris et al. EJNMMI 2013
Some ‘typical’ image artefacts
Edge or ring (Gibbs) artefacts:
• Allways seen with PSF based reconstructions
• Frequently on specific TF systems
(>50% of cases)
• Problems in case using SUVmax
• Mitigation: SUVpeak?
Future directions
• UPICT – uniformity of protocols in clinical trials:
• FDG PET/CT consensus guideline out for public comment (Q4/2013)
• QIBA FDG PET/CT Profile:
• under review/revision
• addresses performance and compliance criteria (systems and users)
Multi-center harmonization of quantification
Main principles of EANM GL and EARL accreditation
• Standardisation of PET examinination –procedure
• Quantification is combination of:
• image resolution
• image noise
• data analysis methods (SUVmax de facto the standard in practice)
• EARL QC’s s based on exploration to find highest common denominator in
• performance of scanner calibration
• SUV-RCs – SUVmax, transition to SUV Peak
• Scanner performance harmonization is feasible on a large scale, but long term
sustainability requires support and service from vendors –goal of SNM-CTN &
EANM/EARL
FDG PET and PET/CT: EANM Procedure Guidelines for
Tumour PET Imaging: version 1.0
Ronald Boellaard, Mike O’Doherty, Wolfgang A. Weber, Felix M. Mottaghy,
Markus N. Lonsdale, Sigrid G. Stroobants, Wim J.G. Oyen, Joerg Kotzerke, Otto
S. Hoekstra, Jan Pruim, Paul K. Marsden, Klaus Tatsch, Corneline J. Hoekstra,
Eric.P. Visser, Bertjan Arends, Fred J. Verzijlbergen, Josee M. Zijlstra, Emile FI
Comans, Adriaan A. Lammertsma, Anne M. Paans, Antoon T. Willemsen,
Thomas Beyer, Andreas Bockisch, Cornelia Schaefer-Prokop, Dominique
Delbeke, Richard P. Baum, Arturo Chiti, Bernd J. Krause.
Eur.J.Nucl.Med.Mol.Imag. 2010
Thank you for your attention !