Molecular Imaging to Identify Predictors of Aortic Valve Disease Activity
Molecular Imaging and Deep Phenotyping to Identify Predictors of AS Disease Activity and Progression
Study Overview
Status
Conditions
Detailed Description
Structural imaging modalities, such as echocardiography (echo) and computed tomography (CT), measure the structural consequences of aortic valvular calcification and have proven invaluable for grading AS severity. However, these techniques cannot capture the dynamic microcalcification processes that drive the underlying disease and have proven insufficient for predicting AS progression. In contrast, molecular imaging using 18F-NaF positron emission tomography/computed tomography (18F-NaF PET/CT) is the gold standard method for non-invasively measuring the central pathophysiological process that drives the progression of AS. This imaging approach uses 18F-sodium fluoride, a tracer that binds preferentially to hydroxyapatite in regions of developing microcalcification. This enables the quantification of microcalcification activity (which precedes visible macrocalcification) and thus provides insights into the underlying disease activity that propels AS progression. Notably, optimized protocols for 18F-NaF PET/CT produce a reproducible biomarker for tracking disease activity and predicting progression. Furthermore, recent advances in PET technology (such as total-body PET scanners) have improved sensitivity by 10- to 40-fold, further enhancing the quantification of the microcalcification rate underlying AS progression.
Overall, the assessment of microcalcification activity shifts the focus from static anatomical assessments to measurement of the dynamic pathological process driving AS progression. However, while 18F-NaF PET/CT is unsuitable for routine clinical use (because it is costly and currently limited to research applications), it can be effectively leveraged to train prediction models and deploy them as clinical calculators that estimate the rate of microcalcification process from readily available biomarker data. The resultant clinical models and calculators could greatly enhance clinical care by detecting patients at risk for rapid progression, refining risk stratification and prognostic accuracy, and opening avenues for personalized monitoring and treatment in calcific AS.
The overarching goal of this Clinical Imaging Study is to develop novel predictive models and clinical calculators that capture AS microcalcification activity and forecast the risk of progressive aortic valve stenosis in individuals with mild to moderate AS. We will achieve this by performing advanced multimodality imaging, including 18F-NaF PET/CT, to quantify microcalcification activity in deeply phenotyped patients using clinical, imaging, and blood plasma biomarkers. Computational approaches, including AI tools, will identify optimal combinations of imaging and non-imaging predictors of microcalcification activity. We will then develop accessible clinical calculators and test the hypothesis that these models and calculators enhance identification of rapid progressors through cross-validation and external validation in the Population Project cohort (which undergoes identical biomarker phenotyping).
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Ahmed Tawakol A Director, MD
- Phone Number: 3699 6177262000
- Email: atawakol@mgh.harvard.edu
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
Males and females aged 18 years or older with mild to moderate calcific AS, as defined by standard echocardiographic criteria.
Exclusion Criteria:
Bicuspid AS, pregnancy, cognitive disabilities that impair the ability to comply with instructions or provide informed consent, or any other medical condition that may undermine participation. Additional exclusion factors will include weight >300 lbs, severe claustrophobia, Pregnancy, and subjects who have had significant radiation exposure as part of research (>2 nuclear tests, computed tomography images, or fluoroscopic procedures) during the preceding 12 months. Further, individuals with renal dysfunction (eGFR<55) or history of allergic reaction to iodinated contrast will not receive the iodinated contrast.
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Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
|---|
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Individuals with mild or moderate aortic stenosis
Mild or moderate aortic stenosis noted on imaging and not expected to undergo treatment of the aortic valve over the next year.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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rate of AS progression
Time Frame: One year
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change of echo- and CT-derived AS measures
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One year
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
Helpful Links
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2026p001100
- 26SFRNPVHD1623048 (Other Grant/Funding Number: American Heart Association)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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