FDG PET/CT

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

Quantitative Imaging Are we there yet?

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

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. 5 Siemens Medical Solutions Molecular Imaging

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

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 www.mimvista.com 7

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

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.

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

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]

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:

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:

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

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

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

FDG-PETCT Technical Committee ROI Definition Group (Tim Turkington) Goal 1 - 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.

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?

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).

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:

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

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 2010-11, Defined in 2008 **Ideal Phantom 2010-11 Current phantom by 2008 Priority H, M, L Quick Hits High

FDG PET/CT

Quantitative Imaging Biomarker Alliance FDG-PET/CT Working Group Report Molecular Imaging and Biology1536-1632 (Print) 1860-2002 (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.

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

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.

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

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