Transcript Slide 1

Quantitative Imaging Biomarker Alliance
PRINCIPAL
LOGISTICAL AND
FINANCIAL
SUPPORT
PROVIDED BY
RSNA
WHY QIBA:
CT SPECIFICS
Corporation Visit
Autumn 2010
<presenter>
<title>
In a poll of 225 top general
internists, CT and MRI were
judged to be the most
important medical advances in
the last 50 years, beating out
life-saving therapies such as
coronary angioplasty and ACE
inhibitors.
Fuchs VR, Sox HC Jr. Physicians' views of the relative importance of thirty
medical innovations. Health Aff, 2001. 20(5): p. 30-42.
Image courtesy of Toshiba
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Why QIBA: CT Specifics
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The Long and Proud History of
Innovation of CT
• 1972: Prototype CT
– Several hrs per slice acquisition; days for reconstruction
• 1974: 1st Generation CT
– 2.5 min/slice
• 1976: Whole-body CT
– 5 sec/slice
• 1989: Helical/Spiral CT
– 0.3 sec/slice; 40 sec for entire chest (40cm Z-axis)
• 1998: 4-row MDCT
– 10 sec for entire chest
• 2002: 16-row MDCT
– 8 sec for entire chest
• 2004: 64-row MDCT
– 5 sec for entire chest
• 20010 and beyond: ?
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Why QIBA: CT Specifics
Image courtesy of Siemens
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Since 2004: Spatial Resolution
up to 2x higher
Non HDCT
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Images courtesy of General Electric
3mm Stent
HDCT
Why QIBA: CT Specifics
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Temporal resolution over 2x
faster
Low Temporal Resolution
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High Temporal Resolution
Why QIBA: CT Specifics
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Stair-step Artifacts up to 80%
Less
Narrow Volume – 64 detector row CT
Wide Volume – 320 detector row CT
Images courtesy of Toshiba
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Why QIBA: CT Specifics
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Image Noise up to 50% Less
60 mAs
Images courtesy of General Electric
60 mAs
Conventional Reconstruction
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HD Reconstruction
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Radiation Dose Reduction
Image courtesy of Siemens
(one example of many promising approaches)
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Multi-energy and Spectral CT
Towards resolving multiple energies and materials
51 keV
Iodine (green) +
Gd (red)
• Automatic separation of iodine contrast
and bone in a mouse
Schlomka et al. Phys Med Biol (2008).
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Image courtesy of Philips
34 keV
Quantitative CT Imaging
• The HU has always been “quantitative”,
• Technical Advances will help us move from
“qualitative image” to “quantitative image”
or measurement
– Longitudinal quantification used to assess
patient response to therapy
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Picture Slide to Demonstrate Effects of
Technology Advancement
• (Jim Mulshine’s suggestion of Reeves slides here)
• Lung lesion with
– 10 mm thick images
– 5 mm thick images
– 2.5 mm thick images
– 1 mm thick images
• Volumetric representation of each
– Showing how blurry and “artifacty”the 10 mm based
image is and how clear the 1mm is.
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Movement to Quantitative
Imaging
• Series of 3 or 4 slides (primarily with pictures)
showing:
– Simple phantom lesion (from 1A?) measured twice
(either same reader twice or two readers)
– Complex phantom lesion measured twice
• Show diameters
• Show volumetric contours
– Simple patient lesion (1B) measured twice
– Complex patient lesion (1B) measured twice
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Use a better example, but ~ like
this
lesion
Reader 1 contour
(includes sliver)
Reader 2 contour
(excludes sliver)
Even with Exquisite images, still uncertainty about what is and isn’t part of a lesion.
This leads to uncertainty in measurements, even with experts.
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Structural Issues Currently Impede
Realization of the Opportunity
Efforts by individual manufacturers to
qualify quantitative imaging applications:
Endpoint
qualification
• Are more costly, and
• Run over longer time periods…
cost
…than the business model of device and
software manufacturers generally support.
Assay
validation
Develop
ment
These issues are exacerbated by lack of
time
clarity in regulatory and reimbursement
policy which increase the risk while
decreasing the incentive
Even when individual companies do these steps,
community need for standards required to address
multi-vendor reproducibility are not accounted for.
June 2010
Autumn
2010
Buckler
Biomedical
LLC
Why QIBA:
CT Specifics
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What we need to Meet the
Opportunity
• Need domain experts:
•
•
•
•
Problem assessment: which problem could be solved by image analysis algorithms
Usability: are the developed algorithms user friendly and really useful for the experts
Feedback from opinion leaders
Market opportunities
• Have to evaluate their hardware/software:
– Standardized image database with annotations
– Definitions of standards
– Evaluation:
•
•
•
•
Phantom data
Clinical trials
Clinical studies
First users (domain expert)
– Cooperation with hardware vendors, because:
•
•
•
•
•
DICOM and other standards
Different vendors / Different image data quality
Interfaces with the hardware of different hardware vendors
Different vendors /Different image data acquisition filters
Different Vendors / Different data representation algorithms and hardware (screen)
• Negotiations etc. with Regulatory (compliance FDA and other international
regulatory)
We Have Three Choices
Don’t Do It
Accept Lower
Utilization and
Reimbursement
Lowest
utilization and
reimbursement
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2010
Do it Individually
Accept Higher Costs
and Lower
Reproducibility
Localized
utilization and
reimbursement
Buckler
Biomedical
LLC
Why QIBA:
CT Specifics
Do it Together
Seek the Win-Win
Structure that
Rewards Participants
Highest
utilization and
reimbursement
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The Need
• Need the appropriate Networks (Groups) in
order to achieve the previous goals
– Because of the
•
•
•
•
•
•
power of cooperation
Exchange experience
Exchange knowledge
Work with the regulatory (like FDA…)
State of the art knowledge
Etc.
June 2010
Autumn
2010
Buckler
Biomedical
LLC
Why QIBA:
CT Specifics
Provide a regulatory pathway
that works in the business
model
Make it familiar to marketing
and give them a product, not
just a cost
Make it actionable for
engineering and R&D,
addressing both design and use
How We Will Succeed
Result:
Widely Available, High Performance, Quantitative Imaging
Imaging Science, Metrology, and Biostatistics
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QIBA Overcomes Obstacles to
Enable the Opportunity
Clinical
Context
Profile
Claims
Ground
work
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2010
Profile
Details
Buckler
Biomedical
LLC
Why QIBA:
CT Specifics
With an IHE-like
certification
reputation
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Profiles are actionable for both
Marketing and R&D
PRODUCT CREATION
PROCESS (PCP)
QIBA PROFILE
Customer
Requirements
Specification (CRS)
I. CLINICAL CONTEXT
II. CLAIMS
III. PROFILE DETAILS
System
Requirements
Specification (SRS)
IV. COMPLIANCE SECTION
V. ACKNOWLEDGEMENTS
Verification Plan
and Protocol
Participation and
visibility
June 2010
Autumn
2010
Buckler
Biomedical
LLC
Why QIBA:
CT Specifics
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Example: Lung Cancer
Make drug development more efective:
• Faster (Window trials—quantitative
endpoint);Cheaper (Adaptive Bayesian
Design, two to three weeks of drug
exposure);Better (Phantom calibration,
standardize method, open source
reference tools, defined molecular targets,
tailored delivery systems)
• Tighter (variance), lighter (dose),
standardized (protocol/profile)
Make care more personalized to patient:
• Clinically proven detection and
longitudinal quantification
• Quantitiative CT measures incorporated
into adaptive therapy / monitoring
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Example: Emphysema and COPD
• Chronic obstructive pulmonary disease
(COPD) is a progressive lung disease
which include emphysema, chronic
bronchitis, refractory (irreversible)
asthma, and severe bronchiectasis.
• 12 million adults have COPD, and
another 12 million are undiagnosed or
developing COPD. It is the fourth leading
cause of death in the U.S., accounting for
126,129 deaths in 2003.
• COPD does not have a cure, but
treatments are currently available to
help individuals manage their symptoms
of COPD
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Utility of CT evaluation of COPD
• A. Dirksen et al., "A randomized clinical trial of alpha(1)-antitrypsin
augmentation therapy," Am J Respir Crit Care Med 160, 1468-1472 (1999).
– “We conclude that lung density measurements by CT may facilitate future
randomized clinical trials of investigational drugs for a disease in which little
progress in therapy has been made in the past 30 yr.”
• In 2009: ”…CT is a more sensitive outcome measure of emphysemamodifying therapy than physiology and health status, and demonstrates a
trend of treatment benefit from alpha(1)-AT augmentation.”
• Present limitations of CT evaluation of emphysema:
– Density measurements vary because level of inspiration varies.
Protocol
– There are inconsistencies between lung density measurements made using
Profile “Target”
different vendor scanners, particularly using contemporary scanners.
– May be associated with differences in CT number scale.
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Profile “Ideal”
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QIBA: Active in Several Aspects
Analyzing/Creating Data to Inform Profiles
QIBA PROFILE
I. CLINICAL CONTEXT
QIBA Experiments and Groundwork
II. CLAIMS
III. PROFILE DETAILS
IV. COMPLIANCE SECTION
V. ACKNOWLEDGEMENTS
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2010
Analyzing:
Effects of Measurement Methods
• 1D, 2D, 3D
• Effects of Slice thickness
• Phantoms
• Apply to Patient Images
• e.g. Coffee Break Experiment
• Standardization across scanners
Buckler
Biomedical
LLC
Why QIBA:
CT Specifics
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QIBA: Active in Several Aspects
UPICT Profiles (Target Concept)
QIBA PROFILE
Acceptable
Target
I. CLINICAL CONTEXT
Ideal
II. CLAIMS
III. PROFILE DETAILS
IV. COMPLIANCE SECTION
V. ACKNOWLEDGEMENTS
Determining Which Parameters (Slice Thickness,
Recon Algorithm, etc.) Affect Measurement Variability
June 2010
Autumn
2010
Buckler
Biomedical
LLC
Why QIBA:
CT Specifics
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<to be fed into profiles>
Requests from John Boone:
1. It was agreed that each vendor would work together with others to come up with a reconstruction kernel which would deliver
consistent spatial resolution (in three dimensions) between scanners. After discussion it was also concluded that the slice
thickness should not be at the limit of resolution, but perhaps in the 1.0 to 1.5 mm slice thickness range. Mike and I felt that to
some extent this is less of an exercise in developing a new kernel and more just finding which existing kernels match the best, but
perhaps some kernel tweaking would be in order. Ultimately this is an exercise in matching MTF(x,y,z) between scanners.
2. we talked about 1024 x 1024 reconstruction, but that was determined to not be feasible, and so that request was dropped.
3. we also talked about HU accuracy - and I believe that all vendors seek to have quantitatively meaningful and accurate HU values,
but with the ever widening collimators this becomes harder to deliver due to scatter. Given that this is already a desire of all
manufacturers, we dropped this as a specific request.
“Wish list” items from PET that also apply to CT
•
Software Version Tracking Use enhanced DICOM attributes to follow version number of software for 1 Acqusition, 2
Reconstruction, 3 post-processing, 4 Display/VOI analysis, 5 Dynamic Analysis Build list (on console) of dates of all s/w versions
•
QA/QC Tracking CT: Daily water equivalent phantom values tracked in DICOM header PET: Daily/weekly/monthly scanner QA
values included in DICOM header PET: Daily (or frequent) uniform cylinder analysis, with link to results in patient DICOM header
Dose calibrator is calibrated for F-18 using NIST-traceable source with information included in patient DICOM header
•
Covariates Wieght - allow disabling of auto wieght import from HIS/RIS Hieght - required field All needed information for
Injected activity (e.g. residual activity, injection time) is required Scanner performs all decay corrections (not the operator) Blood
glucose (from CLIA compliant device) at time of injection is recorded with DICOM patient information All scanner times should
be synchronized to NTP Patient meta-data recorded, e.g. using enhanced DICOM attributes Diplays should have ability to show
information that effects SUVs (uptake time, etc.)
•
Quantitative Reporting Include reference tissue value (e.g. 3 cm diameter VOI in liver) Populate reports from DICOM header
information Mechanism for flagging artifacts (motion, extravasation, etc.)
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<groundwork projects where we need
vendor help>
• Maybe use the process map from qualification
with pointers to areas of vendor involvement
(but showing the whole thing for context)
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Image Archives
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Where We Are Now
Complete Consultative Phase leading to Qualification of VIA
with chest CT for Lung Cancer Clinical Trials
Compose letter and review
Send letter
Follow-up through BQRT meeting
A
Assemble Declaratory information
Write Clinical Context section in Briefing Document
Write literature review sections in Briefing Document
Overlap of
worh other
group
Ower/Dri
ver
Target
date/Status
High
0%
Paul
Q2-10
Medium
High
40%
Paul
High
Low
30%
Andy
Q4-10
Low
High
0%
Paul
Q2-10
Medium
High
40%
Paul
Scope of
Work
Confidence
of Achiving
Low
Other group
alredy doing it
UPICT, CTN
Action/Comments
Write QIBA process section in Briefing Document
B
<phantom task 1>
…
<phantom task n, e.g., write section in Briefing Document>
C
D
E
<Profile task 1, e.g., UPICT consensus protocol>
… (e.g., create non-protocol portions of Profile)
… (e.g., add QIBA subcommittee findings)
Low
Low
<Profile task n, e.g., write section in Briefing Document>
High
High
100%
<process map task 1, e.g., determine what steps are needed>
…
Medium
Low
60%
<process map task n, e.g., write section in Briefing Document>
Low
Med
40%
<clinical performance task 1, e.g., summary of what's ongoing>
… (e.g., compile performance evaluation figures of merit)
Medium
Low
60%
Low
Med
40%
Medium
Low
60%
Low
Med
40%
<clinical performance task n>
Write Results section of Briefing Document
Write Completing the Full Data Package section
Review Briefing Document
Send to agency
Participate in BQRT
Iterate with BQRT
June 2010
Autumn
2010
Buckler
Biomedical
LLC
Why QIBA:
CT Specifics
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What we can do together
• With QIBA in order to achieve their goals concerning VIA:
– Workout the advantages of VIA concerning:
•
•
•
•
Diagnosis
Prognosis
Therapy decision
Therapy success, effect and efficacy, change
In General Context and especially in the Context of
Theranostics = Diagnostics + Therapy
which is a “Strategy requires teamwork, partnering, and tricky regulatory
maneuvering”, The Scientist 2004, 18(16):38, Published 30 August 2004
– Definition and acceptance of Volumetric Changes based on VIA as a standard
BIOMARKER for Volumetric CT
Conclusions
• Utilization of imaging grows as it is used in therapy for predicting and
monitoring response.
• Despite enormous progress and technological possibilities, deployment of
quantitative imaging applications has not kept pace.
• Increased use requires established interpretation and proof of performance.
• Working together according to the QIBA process overcomes structural
hurdles and offers a way forward.
• The process draws from the IHE precedent but is built on
imaging science. Flows and activities are defined to
account for individual stakeholder value propositions.
• New products based on this approach would fuel a
virtuous cycle of innovation with reward to participants.
June 2010
Autumn
2010
Buckler
Biomedical
LLC
Why QIBA:
CT Specifics
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Acknowledgements
•
•
•
•
CT team (all of us)
Daniel Rubin
Matthew Cham
Images provided by:
– General Electric
– Philips
– Siemens
– Toshiba
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