1. FDG PET/CT

2. Monitoring Rx Benefit = Individualized Medicine Convergence of Biomarkers and Diagnostics
H/o Commercial Dx
Individuals - thresholds
Categorical, staging
Workflow/# studies
Binary – choice of Rx
Biomarkers become Dx
Population means, s
Continuous, quantitative
Automation/bias
Longitudinal – monitor Rx
Quantifying the effects of drugs in development
may beg access to biomarkers as diagnostics

3. Quantitative Imaging
Are we there yet?

4. Tumor Tracking Application Simplifying cancer patient management
Compare, analyze, and track tumor progression with up to six sequential PET/CT studies
SUV-based semi -automatic tumor segmentation
Measurement of changes in tumor volume and metabolic activity
Export tables and graphs or 3D contours

5. Longitudinal Quantification in Hybrid Imaging
Reality Today with Siemens syngo TrueD
Visualization 3 Time Points Display MIP Triangulation Gating Support
Quantification 2D/3D Iso-Contouring 1-Click SUVmax RT Structure Export
Trending Trending Charts VOI Propagation Deformable Registration
Innovation is in our genes.
Siemens Medical Solutions Molecular Imaging

6. Automatic co-registration of multiple studies
Automatic segmentation of VOI based on % or SUV
CT or PET-guided lesion definition
Timepoint 3
Timepoint 2
Timepoint 1

7. Therapy Response Assessment
Compare tumors across any number of time points for multiple modalities Gradient-based PET segmentation for more accurate tumor volumes and statistics Export statistics for sharing with referring physicians Accurate registration allows the same region to be compared Difference images highlight variable tumor response 7

8. GE PET VCAR…Powerful Longitudinal Analysis
Automatically register serial studies for longitudinal accuracy
Automatically segment and propagate ROIs for efficiency and robustness
Quantify serial changes with a comprehensive set of metrics (SUV, Total Lesion Glycolysis, Functional Volume) and present in tabulated and graphical form
Export tabulated data for easy utilization in 3rd party analysis routines

9. FDG-PET/CT Technical Committee Aim
The aim of the QIBA FDG-PET/CT Technical Committee is to foster adoption of
pragmatic and cost-effective standards for
accurate and reproducible quantitation of
tumor metabolism via
longitudinal measures by FDG-PET/CT, with
clinical relevance and known sigma.

10. Pattern for PET SUV Measurements as a Biomarker
Digital referenceobject
SUV quantitation and ROI
computation
System and protocol character-ization
Covariates,
data/version tracking,
verification
Patient variability and effect size
Precursor specifications
Serial and multi-center SUV measurements
Profile claims
SUV change analysis
Profile detail specification
Uses:
PET SUVs as a target- and mechanism-specific biomarker of response
Drug development; Business decisions
Drug development; Regulatory decisions
Patient monitoring; Individualization of therapy

11. FDG-PETCT Technical Committee Subcommittee Topics [chair]
Quantitation Computation [David Clunie]
Digital Reference Objects – Images [Paul Kinahan]
Covariates rationale (Normalization) [Yuying Hwang]
RoI Definition (and then Adoption) [Tim Turkington]

12. FDG-PETCT Technical Committee Quantitation Computation (David Clunie)
Pixel Data content
Scaled to SUV ?
Activity concentration ?
Attributes required for SUV scaling or calculation
Standard or private attributes ?
Which ones are populated, and with what (from console) ?
Weight, size (height), sex
Dose total, start, stop
Which time related attributes are used ?
Series, Acquisition, Frame Reference
Decay correction
Has it been applied ?
With reference to which time attribute or condition
Questions asked of vendors:

13. Quantitation Computation
Console data entry
Persistence
Precision
Mapping to DICOM fields
Blood glucose (missing … need new DICOM field)
Other isotopes
Time synchronization issues
Reference to external time standard ?
Correspondence between operator entry versus internal time ?
Injected dose issues
Start versus end times
Residual dose in syringe – time measured distinct from end injection time
Decay correction issues
Multiple bed positions – timing, direction
Start, end or middle of acquisition
Further questions to be asked:

14. FDG-PETCT Technical Committee Digital Reference Object (Paul Kinahan)
Done
Collected PET/CT images of the same reference phantom from scanners from GE, Philips, Siemens
Image data collated and compared w.r.t. DICOM header information
Contacted Mfrs to start discussion of
DICOM information needed
Acceptable process

15. Digital Reference Object
Sample Image Sections from Six Different Scanners
Not meant as a "Consumer's Report" evaluation, but rather to facilitate multi-center comparisons

16. Digital Reference Object
Next Steps:
Initiate manufacturer-driven discussion on methods for distributing and testing a purely digital version of the reference phantom
Test digital reference object on 3rd party review stations
Initiate IHE process for manufacturer-driven roll-out
Explore potential for moving further up the data generation stream, i.e., closer to raw data

17. FDG-PETCT Technical Committee ROI Definition Group (Tim Turkington)
Goal in progress :
To survey the existing ROI capabilities and definitions on workstations being used for PET image interpretation.
Example questions:
Are ROI calculations always performed on original (unzoomed and uninterpolated) pixels?
How are the constituent pixels of small, circular ROI’s determined?
Status: Questionnaire is in final preparation after two iterations of comments from committee members.
Goal 2
To make recommendations for common ROI definitions to be implemented by all vendors.
Goal 3
To guide the implementation of the recommended definitions.

18. What is an ROI? The orange circle is an example.
From the drawn circle, the workstation will tell the user what the FDG uptake was in that region, either
the mean throughout the circle, or
the peak value in the circle.
The zoomed region illustrates things as they actually are, at the level of individual pixels.
How do you decide which pixels go into the mean calculation if the circle doesn't fully include all of them?
There are several points this makes:
1) Generally, what is an ROI? The orange circle is an example. From
the drawn circle, the workstation will tell the user what the FDG uptake was in that region (either the mean throughout the circle, or the peak value in the circle.)
2) The zoomed region illustrates things as they actually are, at the level of individual pixels. One question that's raised is: How do you decide which pixels go into the mean calculation if the circle doesn't fully include all of them?

19. ROI Definition Group Next Steps: Distribute survey to vendors
Collect and summarize results
Based on results, provide recommendations for ROI methods (if any) that are implemented similarly on all available systems.
(long term) Provide recommendations for implementation of more sophisticated ROI techniques (e.g., CT-based ROI’s).

20. FDG-PETCT Technical Committee Covariates Rationale (Yuying Hwang)
Patient compliance parameters
Height and weight (convertible to metric units)
Hours of fasting
Blood glucose level
Scan conditions
PET scan time post FDG injection
Injected dose (decay-corrected, radioactivity and time pre- and post-injection recorded, time synchronized)
Previous scan information if applicable
Intrinsic system operating parameters
Calibration record
QA – Maintenance of operating parameters
System performance characterization
Image processing algorithms
Covariates needed:

21. Covariates Rationale Next Steps (action):
Construct policy guidelines for manufacturers to set requirement on recording and normalizing these covariates

22. Milestones Horizon/PET-CT Beyond RSNA’08
RSNA ’10 and on
RSNA ‘09
Calibration Phantoms
Characterization Lo, Hi rads
RoI Definition*
Dynamic Range lesion size**
RSNA ‘08
Interoperability of
Results Encoding
Image Quality Metrics
Quantitation Computation
Documentation of terms
High
High
Medium
H, M, L
Value
High
High
High
Feasibility
H, M, L
High
Delete me in final draft:
Outputs of the research for each horizon
In general: Align the answers for the four categories under the appropriate 3 headers of Quick Hits, Medium Term, Strategic Plans
Rationale: rationale for research proposed; what each collaborator gets out of the project (fit); what healthcare need is being addressed by the outputs of the project
Product linkage: Point to GEHC products, future products, or market segments that benefit from the research
3rd party interest: Who are key stakeholders for each step of the project from outside GE and SAIC (e.g., pharma, academia, etc)
*Adoption , Defined in 2008
**Ideal Phantom Current phantom by 2008
Priority
H, M, L
Quick Hits
High

23. FDG PET/CT

24. Quantitative Imaging Biomarker Alliance FDG-PET/CT Working Group Report
Molecular Imaging and Biology (Print) (Online)
RSNA News September 2008, Vol 18, No 9
Hallett WA, Maguire RP, McCarthy TJ, Schmidt ME, Young H. Considerations for generic oncology FDG-PET/CT protocol preparation in drug development. IDrugs, 2007 Nov; 10(11):791-6.

25. FDG-PETCT Technical Committee Subcommittees Progress to Date (summary version)
Digital Reference Objects – Images [Paul Kinahan]
Collected PET/CT images of the same reference phantom from scanners from GE, Philips, Siemens
Image data is being collated and compared w.r.t. DICOM header information
Initiated [will do!] manufacturer-driven discussion on methods for distributing and testing a purely digital version of the reference phantom
Harmonized PET/CT reference standard with efforts of AAPM/SNM Task Group 145
Next Steps:
Test digital reference object (DRO) on 3rd party review stations
Initiate IHE process for manufacturer-driven roll-out
Explore potential for moving further up the data generation stream, i.e., closer to raw data
* References

26. FDG-PETCT Technical Committee Subcommittees Progress to Date (summary version)
RoI Definition (and then Adoption) [Tim Turkington]
Set goals of
1) To survey the existing ROI capabilities and definitions on workstations being used for PET image interpretation.
2) To make recommendations for common ROI definitions to be implemented by all vendors.
3) To guide the implementation of the recommended definitions.
The survey is currently being formalized after two iterations of input from committee members. Vendors’ responses will remain anonymous, with only a summary of responses made available, to encourage the greatest degree of candor possible.

27. FDG-PETCT Technical Committee Subcommittees Progress to Date (summary version)
Quantitation Computation [David Clunie]
Objective is to describe how to compute same SUV regardless of vendor, model or version of scanner
Problem is inconsistent use of DICOM pixel data and attributes by vendors
Action to date:
Questions for vendors prepared and agreed to, sent to vendors and responses received from GE, Siemens and Philips
Next actions:
Collate and evaluate responses and iterate with follow up questions
Validate vendors’ responses against reality with images from the field and those vendors have promised to supply
Publish summary document
Add new attributes to DICOM if required

28. FDG-PETCT Technical Committee Subcommittees Progress to Date (summary version)
Covariates rationale (Normalization) [Yuying Hwang]
Identify clinically significant covariates such as patient compliance parameters, scan conditions, and intrinsic system operating parameters
Construct policy guidelines for manufacturers to set requirement on recording and normalizing these covariates
* References