2009 • Volume 1, Number 2
In this issue:
QIBA Collaborates with Imaging Manufacturers
By ANDREW J. BUCKLER, MS
ANALYSIS TOOLS AND
PET SUV from DICOM Images
KINAHAN, PhD, and DAVID CLUNIE, MBBS, FRACR
RSNA 2009 Activities
May 2009 QIBA Meeting
BIOMARKERS IN THE LITERATURE
Search on the Imaging Industry and Biomarkers
IN MY OPINION
QIBA Collaborates with
By ANDREW J. BUCKLER, MS
Efficient, valid methodologies are
required that use imaging biomarkers as surrogate endpoints for changes in the
health status of patients. These methods can be applied in clinical research,
optimal patient care, and development of new therapies, such as
The deployment of qualified imaging
biomarkers has not kept pace with the advances in technology that allow
manufacturers to fulfill demand for them. Large scale deployment has been limited
by variation across manufacturers and lack of consensus about which biomarkers
need to be used and validated.
Efforts by individual manufacturers
to qualify quantitative imaging biomarkers are cost-prohibitive and make it more
difficult to establish the standards needed by the healthcare
QIBA Models Profiles after
As a collaborative alliance, QIBA's goal is to establish a methodology by which
multiple stakeholders test various hypotheses about the technical feasibility and
medical value of imaging biomarkers, starting with volumetric CT,
fluorodeoxyglucose (FDG) PET/CT, and dynamic contrast
materialâ€“enhanced MR imaging.
This process benefits the imaging
device industry by providing a mechanism to share the cost of qualifying mature
biomarkers to increase utilization while also encouraging the development of new,
innovative markers. Broad use of qualified biomarkers to assess treatment
response in clinical practice helps clinicians and patients, while industry
stakeholders such as interventional device companiesâ€”including
radiation therapy and minimally-invasive devices for prevention and
therapyâ€”and biopharmaceutical companies benefit from
cost-effective development programs and more effective use of imaging.
QIBA Technical Committees are
developing Profiles to organize their activity and capture the results. Adapted
from the Integrating the Healthcare Enterprise (IHEÂ®) model, a Profile is a document that specifies
claimsâ€”which tell a user what can be accomplished by following
the Profileâ€”and details, which tell vendors what is required
for their products to comply with the Profile.
After key scientific questions and
concepts requiring validation have been identified and refined, QIBA coordinates
the research and other groundwork needed to resolve these questions so the
Profile definition can proceed.
It is envisioned that manufacturers
will seek to comply with completed Profiles in response to the demand of clinical
users for Profile-compliant equipment. Users will be motivated to require
Profile-compliant devices based on the result of clinical trials that used
Profile-compliant equipment to improve their effectiveness. Increasingly the
standard of care in the clinic will call for these benefits as well.
It is anticipated that this method
will be robust enough to be recognized as a regulatory pathway for the
registration of such products with the FDA. For manufacturers, qualification data
accepted by regulatory bodies could be used in 510(k) applications (or premarket
notifications) more cost effectively than if companies pursued the qualification
Future development and implementation of quantitative imaging relies on
coordination among industry players, regulatory organizations and practicing
clinicians. Patients and the entire healthcare industry will benefit from the
appropriate use of imaging in the diagnosis and management of disease, which can
be supported by validation, standardization, and comparative effectiveness
While manufacturers must remain
attuned to development cost and time-to-market, every stakeholder will benefit
from technological, commercial, and utilization advances in imaging
 Why QIBA is a Good Thing for Radiology in General, and the Imaging
Manufacturers in Particular. Medical Imaging & Technology Alliance
(MITA), February 2009.
Andrew J. Buckler, MS,
is an imaging analytics specialist who has worked in the medical device
manufacturing sector for over 20 years. He serves as co-chair of the QIBA
Volumetric-CT Technical Committee.
ANALYSIS TOOLS & TECHNIQUES
Calculating PET SUV from
By PAUL KINAHAN, PhD, and DAVID CLUNIE, MBBS, FRACR
Although PET/CT imaging of cancer
has recently become a standard component of oncology diagnosis and staging, it
does not necessarily require assessment of numeric pixel values.
Meanwhile, pharmaceutical companies
are using quantitative PET/CT imaging to evaluate potential therapies even though
the FDA has yet to accept the modality as a qualified or validated biomarker for
At the clinical level, the relative
tracer uptake by a lesion is now routinely reported, which creates compelling
reasons to understand and improve the quantitative accuracy of PET/CT
The use of PET/CT to determine
response to therapy is highlighted in the May 2009 supplement to the Journal
of Nuclear Medicine, which includes a comprehensive survey of the factors
that affect the bias and variance of PET/CT imaging. 
Factors Impact Calculation
Numerous factors impact the calculation of uptake values from Digital Imaging and
Communications in Medicine (DICOM) images.
To account for variations in the
injected dose and patient size, generally preferred units for image
interpretation are standardized uptake values (SUVs) defined as
SUV=R/(D/W) where R (kBq/ml) is the activity concentration at
each point, D (kBq) is the decay-corrected injected dose, and W
is the patient weight.
Patient weight is typically used as
a surrogate for the volume of distribution, although the estimated lean body mass
or body surface area is sometimes used instead of weight. Proper calculation of
SUVs, therefore, requires knowledge of several parameters encoded in the image
"header" in addition to the spatially varying activity concentration encoded in
the image pixel data. A partial list of these parameters includes injected dose,
radionuclide half-life (to account for radioactive decay of the isotope), time of
injected dose, time of scan, patient weight, scanner calibration factors, sex
(for lean body mass calculations), height, as well as image scaling methods and
Parameters are encoded in DICOM
header elements of PET images by the scanner as specified by the DICOM Standard.
Some variation exists between scanner manufacturers in how these values are
stored and in which elements they are stored. In principle, the DICOM
Conformance Statement published by the manufacturer should describe these
details and the DICOM Standard defines how different elements should be
interpreted. However, experience has shown that there is room for
misinterpretation, ambiguity, error, and suboptimal choice. For example, the time
to be used for decay correction is potentially stored in several different data
elements, while only one may be appropriate for a given scanner operated in a
A relatively large number of
important data elements are needed for correct calculation of SUVs, which is
further complicated by the need to interpret DICOM images on display station
systems not manufactured by the original scanner provider. Also, the original
scanner provider's workstation may be limited and have the capability to
implement fewer variations in the use of DICOM Standard elements, not support
legitimate variations from other vendors, and consequently may display incorrect
Further, a particular vendor may add
features using private elements understood only by their own systems that modify
the calculation of SUVs and result in different values from those computed
strictly according to the DICOM Standard.
QIBA Studies DICOM
To address these issues, the QIBA FDG-PET/CT Quantitation Computation
subcommittee is evaluating the generation and interpretation of the DICOM data
elements used by the PET/CT scanner manufacturers and display station vendors.
The committee comprises representatives from scanner manufacturers, display
station vendors, pharmaceutical companies, clinical research organizations,
professional societies, physicians, and physicists.
In the first phase, the subcommittee
used surveys to obtain a description of which DICOM data elements were populated
and their expected use from manufacturers and display station vendors. In
addition, a Digital Reference Object (DRO), a set of test DICOM images, is being
constructed to compare SUV measurements on different display stations. Because
the DROâ€”which has demonstrated known
truthâ€”is being used as the test object, results obtained on
different display stations should ideally be identical.
Results of these surveys and studies
are posted at qibawiki.RSNA.org along with
meeting summaries and other information. Comments and participation are always
welcome. The authors acknowledge helpful comments from Jeffrey Yap, PhD, of the
Dana-Farber Cancer Institute.
 Standards for PET Image Acquisition
and Quantitative Data Analysis. J Nucl Med 2009 May; 50 (suppl1):11S-20S.
Boellaard R., et al.
Paul Kinahan, PhD, is
a professor of radiology, bioengineering and electrical engineering and director
of PET/CT physics at the University of Washington in Seattle. He is chair of the
American Association of Physicists in Medicine (AAPM)/SNM Task Group on
Quantitative PET/CT Imaging and participates in SNM, AAPM, and RSNA initiatives
on quantitative medical imaging as a biomarker.
David Clunie, MBBS,
FRACR, is a neuroradiologist and chief technology officer at RadPharm, Inc, which
specializes in independent review and core lab services for imaging clinical
trials for regulatory approval of oncology drugs and biologics. He is editor of
the DICOM Standard, co-chair of the IHE Radiology Technical Committee,
and a participant in the NCI initiative, In Vivo Imaging Workspace of the Cancer
Biomedical Informatics Grid (caBIG®).
RSNA 2009: Quantitative
Imaging/Imaging Biomarkers and QIBA Meetings and Activities
QI/IB Informational Meeting
An overview of imaging biomarkers, the QIBA process, and reports from QIBA
Technical Committees and the Uniform Protocols for Imaging in Clinical Trials
- Monday, November 30, 3:00
QIBA Technical Committee
- Wednesday, December 2, 2:00
THE LAKESIDE LEARNING CENTER (HALL E)
QIBA Technical Committee posters, Meet the Expert sessions, and the QIBA kiosk
will be featured in the Lakeside Learning Center (Hall E) near the Molecular
Imaging Zone and the Toward Quantitative Imaging: Reading Room of the
Future educational showcase.
The Toward Quantitative Imaging:
Reading Room of the Future educational showcase will provide visual and
experiential exposure to quantitative imaging and biomarkers through 15 exhibitor
products that integrate quantitative analysis into the image interpretation
process. Participants can learn through hands-on exhibits featuring informational
posters, computer-based demonstrations, and Meet the Expert presentations
scheduled throughout the week.
QIBA MEETING MARKS YEAR OF
Attendees of QIBA's
May 2009 working meeting were welcomed by N. Reed Dunnick, MD, RSNA Liaison for
Science, who emphasized the RSNA Board of Directors' commitment to QIBA's
activities and future efforts. The May 19-20 workshop was held in Oak Brook,
Chaired by Daniel C. Sullivan, MD,
RSNA Science Advisor, the meeting marked a year of progress towards QIBA's
mission to improve the value and practicality of quantitative imaging biomarkers
by reducing variability across devices, patients, and time.
About 70 stakeholders from the
clinical community, imaging equipment manufacturers, the pharmaceutical industry,
government and medical informatics companies, imaging societies, and RSNA
leadership attended the discussions and Technical Committee breakout sessions
that are highlighted in the meeting summary.
QI/IMAGING BIOMARKERS IN THE
PubMed Search on the
Imaging Industry and Biomarkers
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