The EARL FDG-PET/CT Accreditation Programme & Guideline...

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


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


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

0.0

5000.0

10000.0

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20000.0

[BQML]

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

0.80

0.90

1.00

1.10

1.20

1.30

0.5 1.5 2.5 3.5

GE

Philips

Siemens

~5% outside specs

Results at first testM Maccredited sites

0.7

0.8

0.9

1

1.1

1.2

1.3

0.5 1 1.5 2 2.5 3 3.5

GE

Philips

Siemens

GE

Philips

Siemens

Calibration QC – PET/CT and DC


0.0

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[BQML]

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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1.00

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Sphere volume (ml)

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RC

SUV MAX RC - all vendors

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0.0

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Image Quality % SUV recovery

SUV MAX

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SU

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RC

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)


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 !

The EARL FDG-PET/CT Accreditation Programme & Guideline...

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