FDG PET/CT. Monitoring Rx Benefit = Individualized Medicine Convergence of Biomarkers and...

FDG PET/CT

Monitoring Rx Benefit = Individualized MedicineConvergence of Biomarkers and DiagnosticsH/o Commercial Dx

Individuals - thresholds

Categorical, staging

Workflow/# studies

Binary – choice of Rx

Biomarkers become Dx

Population means,

Continuous, quantitative

Automation/bias

Longitudinal – monitor RxQuantifying the effects of drugs in development

may beg access to biomarkers as diagnostics

Quantitative Imaging

Are we there yet?

Tumor Tracking ApplicationSimplifying 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

Reality Today with Siemens syngo TrueD

Visualization3 Time Points DisplayMIP TriangulationGating Support

Quantification2D/3D Iso-Contouring1-Click SUVmaxRT Structure Export

TrendingTrending ChartsVOI PropagationDeformable Registration

Innovation is in our genes.

5 Siemens Medical Solutions Molecular Imaging

Longitudinal Quantificationin Hybrid Imaging

1. Automatic co-registration of multiple studies

2. Automatic segmentation of VOI based on % or SUV

3. CT or PET-guided lesion definition

Timepoint 3 Timepoint 2 Timepoint 1

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

Therapy Response Assessment

www.mimvista.com

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

GE PET VCAR…Powerful Longitudinal Analysis

FDG-PET/CT Technical CommitteeAim

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.

System and protocol

character-ization

SUV quantitation

and ROIcomputation

Covariates,data/version

tracking,verification

Digital referenceo

bject

Serial and multi-center SUV measurements

SUV change analysis

Profile claims

Profile detail specification

Precursor specifications

Pattern for PET SUV Measurements as a Biomarker

PET SUVs as a target- and mechanism-specific biomarker of responseA. Drug development; Business decisionsB. Drug development; Regulatory decisionsC. Patient monitoring; Individualization of therapy

Patient variability and effect

size

Uses:

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]

1. Pixel Data contenta. Scaled to SUV ?b. Activity concentration ?

2. Attributes required for SUV scaling or calculationa. Standard or private attributes ?b. Which ones are populated, and with what (from

console) ?a. Weight, size (height), sexb. Dose total, start, stop

c. Which time related attributes are used ?a. Series, Acquisition, Frame Reference

3. Decay correctiona. Has it been applied ?b. With reference to which time attribute or condition

FDG-PETCT Technical Committee Quantitation Computation(David Clunie)

Questions asked of vendors:

1. Console data entrya. Persistenceb. Precisionc. Mapping to DICOM fieldsd. Blood glucose (missing … need new DICOM field)e. Other isotopes

2. Time synchronization issuesa. Reference to external time standard ?b. Correspondence between operator entry versus internal

time ?3. Injected dose issues

a. Start versus end timesb. Residual dose in syringe – time measured distinct from

end injection time4. Decay correction issues

a. Multiple bed positions – timing, directionb. Start, end or middle of acquisition

Quantitation Computation

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 ofo DICOM information neededo Acceptable process

Not meant as a "Consumer's Report" evaluation, but rather to facilitate multi-center comparisons

Digital Reference ObjectSample Image Sections from Six Different Scanners

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 CommitteeROI 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:

1) Are ROI calculations always performed on original (unzoomed and uninterpolated) pixels?

2) 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.

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?

What is an ROI?

The orange circle

is an example.

ROI Definition Group

Next Steps:

1. Distribute survey to vendors

2. Collect and summarize results

3. Based on results, provide recommendations for ROI methods (if any) that are implemented similarly on all available systems.

4. (long term) Provide recommendations for implementation of more sophisticated ROI techniques (e.g., CT-based ROI’s).

1. Patient compliance parametersa. Height and weight (convertible to metric units)b. Hours of fastingc. Blood glucose level

2. Scan conditionsa. PET scan time post FDG injectionb. Injected dose (decay-corrected, radioactivity and time

pre- and post-injection recorded, time synchronized)c. Previous scan information if applicable

3. Intrinsic system operating parametersa. Calibration recordb. QA – Maintenance of operating parametersc. System performance characterizationd. Image processing algorithms

FDG-PETCT Technical Committee Covariates Rationale(Yuying Hwang)

Covariates needed:

Covariates Rationale

Construct policy guidelines for manufacturers to set requirement on recording and normalizing these covariates

Next Steps (action):

Milestones Horizon/PET-CTBeyond RSNA’08

Quantitation Computation

Documentation of terms

RSNA ‘08

RSNA ‘09

RSNA ’10 and onF

easi

bilit

yH

, M, L

Val

ueH

, M, L

Prio

rity

H, M

, L

High

Interoperability of

Results Encoding

Image Quality Metrics

Calibration Phantoms

Characterization Lo, Hi rads

RoI Definition*

Dynamic Range lesion size**

High

Medium

High

High

High

High

Quick Hits

High

High

High

High

High

High

*Adoption 2010-11, Defined in 2008

**Ideal Phantom 2010-11 Current phantom by 2008

FDG PET/CT

Quantitative Imaging Biomarker Alliance FDG-PET/CT Working Group Report

RSNA News September 2008, Vol 18, No 9

Molecular Imaging and Biology1536-1632 (Print) 1860-2002 (Online)

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]

1. Collected PET/CT images of the same reference phantom from scanners from GE, Philips, Siemens

2. Image data is being collated and compared w.r.t. DICOM header information

3. Initiated [will do!] manufacturer-driven discussion on methods for distributing and testing a purely digital version of the reference phantom

4. 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]

1. Identify clinically significant covariates such as patient compliance parameters, scan conditions, and intrinsic system operating parameters

2. Construct policy guidelines for manufacturers to set requirement on recording and normalizing these covariates

* References