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Positronium lifetime imaging (PLI) is a newly demonstrated technique possible with time-of-flight (TOF) positron emission tomography (PET), capable of producing an image reflecting the lifetime of the positron, more precisely ortho-positronium (o-Ps), before annihilation, in addition to the traditional uptake image of the PET tracer. Due to the limited time resolution of TOF-PET systems and the added complexities in physics and statistics, lifetime image reconstruction presents a challenge. Recently, we described a maximum-likelihood approach for PLI by considering only o-Ps. In real-world scenarios, other populations of positrons that exhibit different lifetimes also exist. This paper introduces a novel two-component model aimed at enhancing the accuracy of o-Ps lifetime images. Through simulation studies, we compare this new model with the existing single-component model and demonstrate its superior performance in accurately capturing complex lifetime distributions. 

The positronium lifetime imaging (PLI) reconstruction is a technique used in time-of-flight (TOF) positron emission tomography (PET) imaging that involves measuring the lifespan of positronium, which is a metastable electron-positron pair that arises when a PET molecule releases a positron, prior to its annihilation. We have previously developed a maximum likelihood (ML) algorithm for PLI reconstruction and demonstrated that it can generate quantitatively accurate lifetime images for a 570 ps (pico-seconds) TOF PET system. In this study, we conducted further investigations into the statistical properties of the algorithm, including the variability of the reconstruction results, the sensitivity of the algorithm to the number of acquired PLI events and its robustness to hyperparameter choices. Our findings indicate that the proposed ML method produces sufficiently stable lifetime images to enable reliable distinction of regions of interest. Moreover, the number of PLI events required to produce quantitatively accurate lifetime images is computationally plausible. These results demonstrate the potential of our ML algorithm for advancing the capabilities of TOF PET imaging. 

Abstract Quantum systems have entered a competitive regime in which classical computers must make approximations to represent highly entangled quantum states^1,2. However, in this beyond-classically-exact regime, fidelity comparisons between quantum and classical systems have so far been limited to digital quantum devices^2–5, and it remains unsolved how to estimate the actual entanglement content of experiments⁶. Here, we perform fidelity benchmarking and mixed-state entanglement estimation with a 60-atom analogue Rydberg quantum simulator, reaching a high-entanglement entropy regime in which exact classical simulation becomes impractical. Our benchmarking protocol involves extrapolation from comparisons against an approximate classical algorithm, introduced here, with varying entanglement limits. We then develop and demonstrate an estimator of the experimental mixed-state entanglement⁶, finding our experiment is competitive with state-of-the-art digital quantum devices performing random circuit evolution^2–5. Finally, we compare the experimental fidelity against that achieved by various approximate classical algorithms, and find that only the algorithm we introduce is able to keep pace with the experiment on the classical hardware we use. Our results enable a new model for evaluating the ability of both analogue and digital quantum devices to generate entanglement in the beyond-classically-exact regime, and highlight the evolving divide between quantum and classical systems. 

Quantum systems have entered a competitive regime in which classical computers must make approximations to represent highly entangled quantum states1,2. However, in this beyond-classically-exact regime, fidelity comparisons between quantum and classical systems have so far been limited to digital quantum devices2,3,4,5, and it remains unsolved how to estimate the actual entanglement content of experiments6. Here, we perform fidelity benchmarking and mixed-state entanglement estimation with a 60-atom analogue Rydberg quantum simulator, reaching a high-entanglement entropy regime in which exact classical simulation becomes impractical. Our benchmarking protocol involves extrapolation from comparisons against an approximate classical algorithm, introduced here, with varying entanglement limits. We then develop and demonstrate an estimator of the experimental mixed-state entanglement6, finding our experiment is competitive with state-of-the-art digital quantum devices performing random circuit evolution2,3,4,5. Finally, we compare the experimental fidelity against that achieved by various approximate classical algorithms, and find that only the algorithm we introduce is able to keep pace with the experiment on the classical hardware we use. Our results enable a new model for evaluating the ability of both analogue and digital quantum devices to generate entanglement in the beyond-classically-exact regime, and highlight the evolving divide between quantum and classical systems. 

ABSTRACT In Bacillus subtilis , master regulator Spo0A controls several cell-differentiation pathways. Under moderate starvation, phosphorylated Spo0A (Spo0A~P) induces biofilm formation by indirectly activating genes controlling matrix production in a subpopulation of cells via an SinI-SinR-SlrR network. Under severe starvation, Spo0A~P induces sporulation by directly and indirectly regulating sporulation gene expression. However, what determines the heterogeneity of individual cell fates is not fully understood. In particular, it is still unclear why, despite being controlled by a single master regulator, biofilm matrix production and sporulation seem mutually exclusive on a single-cell level. In this work, with mathematical modeling, we showed that the fluctuations in the growth rate and the intrinsic noise amplified by the bistability in the SinI-SinR-SlrR network could explain the single-cell distribution of matrix production. Moreover, we predicted an incoherent feed-forward loop; the decrease in the cellular growth rate first activates matrix production by increasing in Spo0A phosphorylation level but then represses it via changing the relative concentrations of SinR and SlrR. Experimental data provide evidence to support model predictions. In particular, we demonstrate how the degree to which matrix production and sporulation appear mutually exclusive is affected by genetic perturbations. IMPORTANCE The mechanisms of cell-fate decisions are fundamental to our understanding of multicellular organisms and bacterial communities. However, even for the best-studied model systems we still lack a complete picture of how phenotypic heterogeneity of genetically identical cells is controlled. Here, using B. subtilis as a model system, we employ a combination of mathematical modeling and experiments to explain the population-level dynamics and single-cell level heterogeneity of matrix gene expression. The results demonstrate how the two cell fates, biofilm matrix production and sporulation, can appear mutually exclusive without explicitly inhibiting one another. Such a mechanism could be used in a wide range of other biological systems.