First ex-vivo positronium imaging of tissues with modular J-PET scanner using $^{44}$Sc radionuclide

This study presents the first ex-vivo positronium imaging of human tissues using the modular J-PET scanner with the $^{44}$Sc radionuclide. The $^{44}$Sc isotope was produced via the $^{44}$Ca(p, n)$^{44}$Sc nuclear reaction and used to perform positronium imaging of phantom composed of human adipose tissue, cardiac myxoma tissue, thrombi blood clot, and also porous polymer XAD4, and a certified reference material (CRM) made from fused silica. The experiment demonstrates the suitability of $^{44}$Sc as a positron source for positronium imaging. The performance of J-PET for positronium imaging with $^{44}$Sc was validated by proper reconstruction of the mean orthopositronium lifetime for CRM material and XAD-4 polymer. The mean ortho-positronium (oPs) lifetimes determined for adipose tissue, cardiac myxoma tissues and thrombi were consistent with results of previous experiments. The study highlights the potential $^{44}$Sc radionuclide for positronium lifetime imaging (PLI).

💡 Research Summary

This paper reports the first ex‑vivo positronium imaging of human tissues using the modular J‑PET scanner together with the radionuclide ^44Sc. Positronium, a bound state of an electron and a positron, exists in two spin configurations: para‑positronium (p‑Ps) with a very short lifetime (~125 ps) and ortho‑positronium (o‑Ps) with a longer lifetime (~142 ns) that is highly sensitive to the surrounding free volume and oxygen concentration. Conventional PET detects only the two 511 keV photons from direct annihilation, ignoring the information carried by positronium formation and decay. Recent advances have shown that measuring the o‑Ps lifetime can provide a novel biomarker of tissue micro‑structure, potentially enabling early detection of pathological changes.

The authors selected ^44Sc as the positron source because it combines a high β⁺ branching ratio (≈94.3 %) with a prompt 1157 keV γ‑ray emitted in virtually every decay (≈100 %). This dual‑photon emission facilitates simultaneous detection of the annihilation photons and the prompt γ, which is essential for accurate time‑of‑flight and multi‑photon correlation measurements. Moreover, ^44Sc has a clinically convenient half‑life of about 4 h, avoiding the long‑term radiation burden of ^22Na and the low prompt‑γ yield of ^68Ga, ^124I, or ^82Rb.

^44Sc was produced via the ^44Ca(p,n)^44Sc reaction at the Heavy Ion Laboratory of the University of Warsaw. A calcium carbonate target was bombarded for 2 h 25 min with a 10.6 mA proton beam, yielding a solution with an activity of 7.085 MBq. Chemical processing involved dissolution in HCl, filtration to remove graphite particles, and pH adjustment to keep the solution mildly acidic (pH ≈ 4) to prevent corrosion of the plastic phantom containers.

Five phantoms were prepared: human adipose tissue, cardiac myxoma tissue, thrombus (blood clot), a porous polymer (XAD‑4), and a certified reference material (CRM) made of fused silica with a known o‑Ps lifetime. Each phantom received 0.25 mL of the ^44Sc solution (≈7 MBq) and was sealed in 5 mL Eppendorf tubes. The placement of the phantoms inside the J‑PET detector was verified by micro‑CT (Bruker SkyScan 1172) after staining with Lugol’s solution for soft‑tissue contrast.

The modular J‑PET scanner consists of 24 detector modules arranged in a cylindrical geometry (diameter ≈ 74 cm). Each module contains 13 plastic scintillator strips (50 cm × 6 mm × 24 mm). The total detector weight is ~60 kg, making the system lightweight, portable, and cost‑effective (approximately five times cheaper than crystal‑based PET scanners). Plastic scintillators provide excellent timing resolution and, crucially, enable multi‑photon detection: the 511 keV annihilation photons and the prompt 1157 keV γ can be recorded in coincidence, allowing discrimination of o‑Ps three‑photon decays.

Data were acquired for 6 hours, collecting about 3.97 million coincidence events. The time differences between the prompt γ and the annihilation photons were histogrammed in a 50 ns window to generate a positronium annihilation lifetime spectrum (PALS). The spectrum was modeled as a sum of three exponential components (p‑Ps, direct annihilation, o‑Ps) convolved with a Gaussian resolution function. Fitting was performed using OriginLab software with the following parameters: background level, normalization coefficients, Gaussian width (σ), offset, and the three lifetimes (τ1, τ2, τ3). The longest component (τ3) corresponds to the o‑Ps lifetime.

Results showed that the CRM yielded an average o‑Ps lifetime of 2.92 ns, and XAD‑4 gave 3.45 ns, both in excellent agreement with literature values, confirming the calibration of the system. The biological samples produced lifetimes of 2.71 ns (adipose tissue), 2.66 ns (cardiac myxoma), and 2.58 ns (thrombus), matching previously reported ex‑vivo and in‑vivo measurements. These findings demonstrate that the J‑PET scanner, despite using plastic scintillators, can accurately resolve o‑Ps lifetimes when paired with a suitable radionuclide like ^44Sc.

The discussion emphasizes several key points. First, ^44Sc’s high β⁺/γ coincidence rate and moderate half‑life make it an optimal tracer for positronium lifetime imaging, overcoming the limitations of other isotopes. Second, the modular J‑PET design provides a low‑cost, scalable platform that can be upgraded to full‑body configurations while retaining multi‑photon capabilities. Third, the ability to measure o‑Ps lifetimes ex‑vivo paves the way for in‑vivo applications, where variations in free‑volume size and oxygen concentration could serve as early biomarkers for cancer, thrombosis, inflammation, and other pathologies.

In conclusion, the study validates the feasibility of ex‑vivo positronium imaging using a modular J‑PET scanner and ^44Sc. It establishes a workflow—from isotope production and chemical purification to phantom preparation, micro‑CT verification, data acquisition, and lifetime analysis—that can be translated to clinical settings. Future work will focus on extending the technique to in‑vivo studies, optimizing detector geometry for whole‑body imaging, and exploring additional radionuclides with favorable β⁺/γ characteristics. The combination of ^44Sc and J‑PET thus represents a promising avenue for introducing positronium lifetime imaging into routine medical diagnostics.