Machine-learning tools extracted information about the spleen from patient MRI scans.
Image Credit: Kamineni M et al., Science Translational Medicine, Sept. 2026.
Scientific Frontline: Extended "At a Glance" Summary: The Spleen and Coronary Artery Disease
The Core Concept: Researchers have identified specific structural features in the spleen, visible on MRI scans, that are associated with an increased risk of coronary artery disease (CAD).
Key Distinction/Mechanism: Unlike traditional CAD assessments that focus on the heart and blood vessels directly, this approach uses artificial intelligence to analyze nuanced changes in the spleen, a central hub of the blood-forming system. It links these physical variations (like irregular texture) to genetic variants already known to increase CAD risk.
Major Frameworks/Components:
- Artificial Intelligence and Imaging: The study utilized AI tools to analyze abdominal MRI scans from 42,059 participants in the UK Biobank, extracting 107 splenic features, ten of which correlated with CAD.
- Genomic Analysis: Genome-wide association analyses confirmed that genes linked to both these splenic features and CAD are involved in inflammation, smooth muscle cell function, hypertension, and fat cell formation.
- Non-Coding Regulatory Regions: Many of the associated genetic variants were located in non-coding regions of the genome. Specifically, two variants on chromosome 9 were linked to irregular spleen texture and increased CAD risk, independent of conventional risk factors like cholesterol.
Branch of Science: Cardiology, Genetics, Computational Biology, Artificial Intelligence (Machine Learning), and Radiology.
Future Application: The discovery provides potential new therapeutic targets for preventing and treating CAD by addressing the spleen's role in the disease process. It also suggests that routine abdominal imaging could eventually provide early warnings for heart disease risk.
Why It Matters: Coronary artery disease remains the leading cause of death globally. Identifying the spleen as a contributing factor and potential indicator opens new, unexplored avenues for understanding and combating the disease.
Certain features in the spleen hidden within imaging scans may signal a person’s risk of coronary artery disease (CAD), according to a new study led by Harvard Medical School investigators at Massachusetts General Hospital.
The work helps answer the question of whether and how the spleen plays a role in CAD risk and suggests new targets for preventing and treating what remains the world’s leading cause of death.
Hidden in Plain Sight
The research team looked to existing MRI scans of patients’ spleens to see what information could be extracted about this understudied organ’s association with plaque buildup in the arteries that supply the heart. Scientists have been trying to pin down the link for decades, given the spleen’s involvement in filtering blood, protecting against infection, and regulating inflammation, blood pressure, and smooth muscle cells.
“Evidence increasingly ties the blood-forming system to heart disease, and the spleen is a central hub of that system, storing and filtering blood and producing immune and inflammatory cells,” said co-senior author Zhi Yu, Harvard Medical School assistant professor of medicine at Massachusetts General Hospital. “But the spleen is hard to assess through routine tests, so imaging is a powerful way to see nuanced changes in the organ and ask whether they reflect, or even forecast, disease.”
To investigate, Yu and colleagues leveraged artificial intelligence–based tools, abdominal imaging, and clinical outcomes data to identify splenic features relevant to CAD. They also performed genomic analyses to see if known CAD-associated genes are linked to splenic features seen in their imaging data.
The team’s research drew on information from 42,059 participants in the UK Biobank.
Of the 107 splenic features observed on abdominal imaging scans, 10 were associated with CAD.
Genome-wide association analyses identified genes linked to both splenic features and CAD. These genes were often involved in processes such as inflammation, smooth muscle cell function, hypertension, and fat cell formation. Many of the associated variants fell in noncoding, regulatory regions of the genome. Two variants on chromosome 9 were associated with a nonuniform, irregular texture in the spleen and increased odds of CAD, independent of blood pressure, cholesterol, and other conventional risk factors.
Testing the Findings in Clinical Care
To see how these general-population findings held up in patients, the team tested whether the UK Biobank patterns would also appear in people imaged as part of routine clinical care.
Among 2,745 patients from the Mass General Brigham Biobank, most associations did not carry over. The authors suspect this is in part because research cohorts like the UK Biobank tend to be healthier and are scanned under uniform protocols, whereas clinical patients tend to have more complex medical histories and are imaged under widely varying protocols. The UK Biobank and Mass General Brigham settings may capture genuinely different biological states, they said.
“The cohort and protocol differences are likely a major driver of why our findings in the UK Biobank weren’t replicated in the clinical data set,” said Yu. “But that doesn’t mean the findings are not generalizable. There is strong validation of the gene variants within the UK Biobank, and the genetics converge with independent observations in biology.”
Further work, such as applying more consistent imaging protocols to a clinical cohort, can strengthen confidence in the visual and genetic associations the team uncovered or weed out any that reflect chance, the authors said.
“These findings shed light on novel mechanisms linking the spleen to CAD, providing potential targets for therapeutic intervention to address this unexplored axis,” said first author Meghana Kamineni, Harvard Medical School clinical fellow in medicine at Massachusetts General Hospital.
Funding: This research was funded in part by the Harvard-MIT Health Sciences and Technology program, the HMS Office of Scholarly Engagement, the American Heart Association (Career Development Award 935176, 18SFRN34110082), a Harvard Catalyst K12 Award, Bayer AG, Fondation Leducq (14CVD01, TNE-18CVD04), the National Institutes of Health (1K01HL168231, 1R01HL092577, K24HL105780, 1R01HL134892, 1R01HL163099-01, R01AG063839, R01HL151627, R01HL157073, R01HL166538, 1K99HG012956-01, R01HL142711, R01HL127564, R01HL148050, R01HL151283, R01HL148565, R01HL135242, R01HL151152, and R01DK125782), the RRM Charitable Fund, the Simard Fund, and Massachusetts General Hospital through the Paul and Phyllis Fireman Endowed Chair in Vascular Medicine.
Published in journal: Science Translational Medicine
Authors: Meghana Kamineni, Vineet Raghu, Zhanqing Hua, Haodong Tian, Buu Truong, Ahmed Alaa, Art Schuermans, Sam Friedman, Christopher Reeder, Romit Bhattacharya, Peter Libby, Patrick T. Ellinor, Mahnaz Maddah, Anthony Philippakis, Whitney Hornsby, Zhi Yu, and Pradeep Natarajan
Source/Credit: Harvard Medical School | Mass General Brigham
Edited by: Scientific Frontline
Reference Number: med091226_01
