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| Main Authors: | , , , , , , , , , , |
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| Format: | Preprint |
| Published: |
2026
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| Subjects: | |
| Online Access: | https://arxiv.org/abs/2601.17192 |
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Table of Contents:
- More than 10 million coronary angiograms are performed globally each year, providing a gold standard for detecting obstructive coronary artery disease. Yet, no obstructive lesions are identified in 70% of patients evaluated for ischemic heart disease. Up to half of these patients have undiagnosed, life-limiting coronary microvascular dysfunction (CMD), which remains under-detected due to the limited availability of invasive tools required to measure coronary flow reserve (CFR). Here, we introduce PUNCH, a non-invasive, uncertainty-aware framework for estimating CFR directly from standard coronary angiography. PUNCH integrates physics-informed neural networks with variational inference to infer coronary blood flow from first-principles models of contrast transport, without requiring ground-truth flow measurements or population-level training. The pipeline runs in approximately three minutes per patient on a single GPU. Validated on synthetic angiograms with controlled noise and imaging artifacts, as well as on clinical bolus thermodilution data from 20 patients, PUNCH demonstrates accurate and uncertainty-calibrated CFR estimation. This approach establishes a new paradigm for CMD diagnosis and illustrates how physics-informed inference can substantially expand the diagnostic utility of available clinical imaging.