Cardiac positronium lifetime in human PET: a reproducible right–left ventricular contrast that is not explained by blood oxygenation
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Background
Ortho-positronium (o-Ps) lifetime, now measurable in vivo on long-axial-field-of-view (LAFOV) PET/CT, has been proposed as a biomarker of tissue oxygenation and hypoxia. Because o-Ps lifetime is dominated by tissue free-volume structure while the oxygen-specific contribution is small, whether an in-vivo lifetime contrast reflects oxygenation rather than anatomy is an open, identifiability-limited question.
Aim
To test the oxygenation hypothesis directly using the heart’s natural arterial/venous oxygenation contrast, with a built-in anatomical control.
Methods
We re-analysed a public [ 82 Rb]Cl human cardiac LAFOV PET/CT dataset (5.30 × 10 8 evaluated three-photon events). Per-compartment o-Ps lifetimes were extracted with a background-plus-two-component exponentially-modified-Gaussian (EMG) model. The list-mode→image mapping and right/left ventricle (RV/LV) identity were established lifetime-free (the mapping reproduces the provider’s reconstructed image at block-correlation 0.998 and wins a joint multi-organ alignment panel). We applied a confound battery — registration stress test, blood-core vs wall, lung-air and wall-myocardium partial-volume, tissue density — and a structure/position-matched control (pulmonary artery, deoxygenated, vs aorta, oxygenated). An isotope-matched 82 Rb uniform-quartz reference bounded the instrument’s positional behaviour. All results were produced by two independent analysis pipelines.
Results
RV o-Ps lifetime exceeded LV by Δτ = +0.304 ns (RV 1.700 ± 0.172, LV 1.396 ± 0.130 ns; ~1.4 σ ), in the oxygen-expected direction; the contrast was stable across ± 16 mm registration perturbation (sign preserved in 100% of 342 shifts) and resided in the blood core, not the wall. However, the matched-vessel control was null: pulmonary artery - aorta = -0.011 ± 0.344 ns. Lung-air and wall-myocardium partial-volume were disfavoured, and the effect fell within the isotope-matched 82 Rb instrumental positional envelope (~0.1–0.35 ns over 40 mm in uniform material).
Conclusion
On this single subject, the cardiac o-Ps lifetime contrast does not provide a clean readout of blood oxygenation: an oxygenation effect of the observed (~0.3 ns) magnitude is ruled out by the matched control, while a small physiological effect cannot be excluded. We provide a reusable confound-control battery for evaluating future in-vivo o-Ps oxygenation claims. Multi-subject replication with anatomy decoupled from oxygenation is required.
