# Molecular Calcification Imaging and Ascending Aortic Disease in Patients With a Bicuspid Aortic Valve

**Authors:** Jennifer Nash, Samuel Debono, Krithika Loganath, Beth Whittington, Evangelos Tzolos, Maaz Syed, Laura Clark, Tijana Mitić, Adriana A. S. Tavares, Mark Macaskill, Stephanie L. Sellers, Tim Clark, Scott Semple, Gillian MacNaught, Edwin J. R. van Beek, Damini Dey, Piotr Slomka, Niki Walker, Jillian Madine, Mark Field, Riaz Akhtar, Rachael O. Forsythe, Michelle C. Williams, Marc R. Dweck, David E. Newby, Alexander J. Fletcher

PMC · DOI: 10.1001/jamanetworkopen.2025.60385 · JAMA Network Open · 2026-02-23

## TL;DR

This study shows that [18F]-sodium fluoride PET imaging can detect aortic wall disease activity in patients with a bicuspid aortic valve, potentially improving surgical decision-making.

## Contribution

The study introduces [18F]-sodium fluoride PET as a novel noninvasive method to assess aortic disease progression in bicuspid aortic valve patients.

## Key findings

- Low [18F]-sodium fluoride uptake was linked to faster aortic growth independent of baseline diameter.
- High [18F]-sodium fluoride uptake was associated with a stiffer, slow-growing aortic wall.
- PET imaging identified microcalcification and disease activity in the ascending aorta.

## Abstract

Can fluorine F 18–labeled ([18F])–sodium fluoride positron emission tomography help identify a diseased aortic wall in patients with a bicuspid aortic valve?

In this cohort study of 76 participants with a bicuspid aortic valve, low aortic wall [18F]–sodium fluoride uptake was associated with faster ascending aortic growth rate independent of baseline diameter. Higher [18F]–sodium fluoride uptake was also associated with a stiff and slow growing aortic wall phenotype.

These findings suggest that [18F]–sodium fluoride can identify disease activity within the ascending aorta, with the potential to improve patient selection for prophylactic aortic surgery.

This cohort study examines whether positron emission tomography imaging with [18F]–sodium fluoride can detect aortopathy, identify disease severity, and estimate disease progression in patients with a bicuspid aortic valve.

Selection of patients with a bicuspid aortic valve and aortopathy for prophylactic aortic surgery remains challenging. In thoracic aortopathy, aortic medial elastin fiber fragmentation initially leads to microcalcification but later declines with progressive loss of elastin content and reduced structural integrity.

To determine whether aortic microcalcification detected using fluorine F 18–labeled [18F]–sodium fluoride positron emission tomography (PET) is associated with future aortic diameter expansion.

This prospective longitudinal cohort study was conducted in tertiary care centers across Scotland from April 4, 2019, to September 15, 2023. Participants included patients with a bicuspid aortic valve. Data analysis was performed from May 21, 2024, to March 4, 2025.

Hybrid [18F]–sodium fluoride PET and computed tomography.

Baseline ascending aortic [18F]–sodium fluoride uptake was measured as mean tissue to background ratio. The primary outcome was ascending aortic diameter expansion during 24 months on cardiac magnetic resonance imaging (MRI).

Seventy-six patients with a bicuspid aortic valve (mean [SD] age, 52.6 [7.5] years; 57 [75.0%] male) underwent baseline [18F]–sodium fluoride PET and MRI. Fifty-six patients underwent follow-up MRI after a median of 723 (IQR, 515-787) days. There was an inverse correlation between baseline ascending aortic [18F]–sodium fluoride uptake and annual change in diameter (Pearson r = −0.37; P = .005), which remained after adjustment for confounders in multivariable regression analysis. Ascending aortic [18F]–sodium fluoride was not correlated with baseline diameter (Pearson r = 0.08; P = .50) but was moderately correlated with baseline ascending aortic stiffness index (Pearson r = 0.38; P < .001).

In this cohort study of patients with a bicuspid aortic valve, the most rapid aortic growth was seen in those with low [18F]–sodium fluoride ascending aortic uptake, indicating reduced aortic wall integrity. High ascending aortic [18F]–sodium fluoride uptake was associated with a stiffer and slow-growing ascending aortic phenotype. These findings suggest that [18F]–sodium fluoride PET imaging represents a promising new noninvasive approach to identify a microcalcified disease phenotype in thoracic aortopathy among patients with a bicuspid aortic valve.

## Linked entities

- **Chemicals:** [18F]-sodium fluoride (PubChem CID 23690531)

## Full-text entities

- **Genes:** ELN (elastin) [NCBI Gene 2006] {aka ADCL1, SVAS, WBS, WS}
- **Diseases:** medial calcification (MESH:D050380), Bicuspid Aortic Valve (MESH:D000082882), bicuspid thoracic aortopathy (MESH:D013899), aortic regurgitation (MESH:D001022), type 2 diabetes (MESH:D003924), calcium (MESH:D002128), ascending aortic aneurysm (MESH:D000094625), Aortic dilation (MESH:D002311), connective tissue disease (MESH:D003240), Hypertension (MESH:D006973), stiffness (MESH:C566112), atherosclerosis (MESH:D050197), stenosis (MESH:D003251), stroke (MESH:D020521), contrast allergy (MESH:D005119), Valve stenosis (MESH:D001024), aneurysm (MESH:D000783), coarctation (MESH:D001017), Thoracic aortic microcalcification (MESH:D002114), Thoracic aortopathy (MESH:D013896), Stanford type A aortic dissection (MESH:D000784), diabetes (MESH:D003920), Valve regurgitation (MESH:D006349), Aortic Disease (MESH:D001018)
- **Chemicals:** calcium (MESH:D002118), gadolinium (MESH:D005682), hydroxyapatite (MESH:D017886), Ca10 [PO4]6 [OH]2 (-), Fluorine F 18- (MESH:C000615276)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12931472/full.md

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Source: https://tomesphere.com/paper/PMC12931472