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Positronium Lifetime Imaging with the Biograph Vision Quadra using 124I

T0 review · 4 major / 6 minor · reviewed 2026-08-10 · deepseek-v4-flash

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Pith's one-line read Voxel-wise positronium lifetime imaging is feasible on a commercial PET/CT scanner with 124I down to 4 mm voxels.

desk verdict A credible phantom demonstration of 4 mm voxel oPs lifetime imaging on a commercial LAFOV PET/CT, but the activity-concentration clause of the feasibility claim outruns the data. read the letter →

arxiv 2501.04145 v1 pith:YUKGXS42 submitted 2025-01-07 physics.med-ph

Lorenzo Mercolli , William M. Steinberger , Narendra Rathod , Maurizio Conti , Pawe{l} Moskal , Axel Rominger , Robert Seifert , Kuangyu Shi
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Ewa {L}. Stępień Hasan Sari
This is my paper · ORCID
classification physics.med-ph
keywords PositroniumlifetimeimagingLongaxialfield-of-viewPET/CT124Iortho-positroniumtime-of-flightlocalizationvoxel-wisefittingBayesianAmberliteXAD4phantom
verification ladder T0 review T1 audit T2 compute T3 formal

The pith

A machine-rendered reading of the paper's core claim, the machinery that carries it, and where it could break.

The reading

The paper aims to show that voxel-wise ortho-positronium (oPs) lifetime imaging is feasible on a commercial long-axial field-of-view PET/CT scanner under conditions close to clinical routine. Using $^{124}$I as the source and the scanner's ability to detect its 602.7 keV prompt gamma, the authors locate three-gamma annihilation events by time-of-flight and fit the oPs lifetime per voxel with a Bayesian model. In phantom measurements with four Amberlite XAD4/water samples, they recover bulk lifetimes from 1.82 ns to 2.52 ns and, for well-separated samples, distinguish the samples even at 4 mm voxel size. The claim matters because oPs lifetime is sensitive to oxygen, pH, and tissue pathology, so a voxel-wise lifetime map could add diagnostic information to an ordinary PET scan without new hardware.

What carries the argument

The enabling mechanism is the selection of three-gamma events (3γE) from $^{124}$I decay: $^{124}$I emits a 602.73 keV prompt gamma with 62.9% branching ratio, and the scanner's energy resolution separates it from the two 511 keV annihilation photons. Each 3γE is located in space by the time-of-flight difference between the two annihilation photons, no tomographic reconstruction is used, and the time difference between the annihilation photons and the prompt gamma is binned into a time-difference distribution (TDD) per voxel. The oPs lifetime $\tau_3$ is extracted by a Bayesian fit of a Gaussian convolved with three lifetime components (para-positronium, direct annihilation, and oPs) to the TDD, with fixed pPs and direct lifetimes (125 ps and 388 ps) and priors as specified in the paper.

What would settle it

Scan a two-material phantom whose oPs lifetimes differ by about 1 ns with a sharp interface, using the same $^{124}$I activity and 4 mm voxels, and compare the central-voxel lifetime of each material with its bulk lifetime from a single-tube fit; if the central-voxel value shifts by more than the quoted statistical uncertainty when the neighbouring material is swapped, then TOF mislocalization contaminates the voxel result and the feasibility claim weakens.

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Extended reading notes

Core claim

The central claim is that positronium lifetime imaging — a three-dimensional image whose voxel values are the ortho-positronium lifetime $\tau_3$ — is feasible with a commercial PET/CT scanner (the Biograph Vision Quadra) using $^{124}$I at activity concentrations, scan times, and voxel sizes compatible with clinical use. The evidence is a set of phantom scans in which four sample tubes with different oPs lifetimes ($2.52 \pm 0.03$, $2.37 \pm 0.03$, $2.27 \pm 0.04$, and $1.82 \pm 0.02$ ns for the whole samples) were imaged both separated and taped together. With the samples separated, even $4.0 \times 4.0 \times 4.0$ mm$^3$ voxels yield clearly distinguishable lifetime values in the central voxels, with relative uncertainties around 10%; with the samples in contact, the spatial distinction is harder and the authors attribute the limitation mainly to the TOF-based localization accuracy of three-gamma events rather than to counting statistics. The paper concludes that diagnostic-level oPs lifetime imaging using $^{124}$I-based compounds is achievable on this class of scanner.

Load-bearing premise

The load-bearing assumption is that the time-of-flight localization of each three-gamma event places it in the correct 4 mm voxel; if events are mislocalized by more than a voxel, the measured voxel lifetime is a mixture of neighboring materials' lifetimes rather than the true local value.

Editorial extensions

If this is right

  • Existing LAFOV PET/CT systems could produce oPs lifetime maps without hardware changes, turning a standard 124I scan into a tissue-microenvironment imaging study.
  • The demonstrated whole-sample precision (relative τ3 uncertainty below 1.8% at ~232 kBq/ml in 15 minutes) indicates that clinically realistic activities suffice for voxel-level fitting.
  • The ability to resolve lifetime differences around 0.1 ns at 4 mm voxels suggests that oxygen- or pH-related contrast could be mapped at the scale of tumor heterogeneity.
  • The main obstacle to imaging adjacent regions with different lifetimes is TOF localization accuracy, so improved coincidence timing or statistical image reconstruction should directly improve the lifetime maps.

Reading between the lines

Editorial extensions of the paper, not claims the author makes directly.

  • A natural next test is to lower the activity toward the 10-70 kBq/ml range reported in thyroid cancer metastases to see whether voxel-level precision degrades gracefully; the current phantom used about 232 kBq/ml.
  • If TOF localization is the bottleneck, the contamination between adjacent materials should scale with the ratio of TOF uncertainty to voxel size, a prediction that could be checked with existing data by varying the voxel size and measuring boundary sharpness.
  • The fixed τ1 and τ2 values (125 ps and 388 ps) may be a subtle bias source: for a homogeneous phantom with a known lifetime, a joint fit of all three lifetimes would reveal whether fixing them distorts τ3 in tissue-like materials.
  • The method's success with well-separated sources raises the possibility that a simple spatial-regularization or smoothing step could rescue the taped-together case, potentially making the distinction of adjacent lesions possible without hardware changes.
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Editorial analysis

A structured set of objections, weighed in public.

Desk editor's note, referee report, and a circularity audit.

Referee Report

4 major / 6 minor

Summary. This manuscript reports phantom measurements of ortho-positronium (oPs) lifetime imaging on a commercial long-axial field-of-view PET/CT scanner (Biograph Vision Quadra) using 124I. Four tubes with different mixtures of Amberlite XAD4 and water, each spiked with 1.12–1.44 MBq of [124I]NaI (≈232 kBq/ml), were scanned in two configurations: separated by several centimeters (15 min) and taped together (40 min). The authors fit a Bayesian three-lifetime model to time-difference distributions of three-photon events localized by time-of-flight, obtaining whole-tube oPs lifetimes of 1.82–2.52 ns with <1.76% relative uncertainty, and voxel-wise lifetime maps at 10.0, 7.1, and 4.0 mm voxel sizes. The separated-tube images show visual differences in τ3 across tubes, while the taped-together images do not allow clear spatial distinction. The paper concludes that oPs lifetime imaging is feasible on a commercial PET/CT under clinically viable conditions with 124I.

Significance. If fully supported, this result would be significant: it would show that voxel-wise oPs lifetime imaging is possible on an unmodified clinical PET/CT scanner using a clinically available isotope (124I), without custom hardware, and the XAD4 phantom provides a simple recipe for intercomparison studies. Strengths include the high precision of the whole-tube fits, the systematic exploration of three voxel sizes, the use of Bayesian fitting with explicit priors, and the availability of evaluated data on Zenodo. The authors also honestly report the main limitations in the Discussion (activity concentration higher than clinical uptake, TOF localization as limiting factor, and poor separation in the taped-tube setup). However, the central conclusion overstates what is demonstrated: the scanned activity concentration is 3–20 times higher than the clinical values cited by the authors themselves, and the voxel-level distinction between similar samples is not statistically established. The clinical-feasibility claim therefore needs revision or additional supporting evidence.

major comments (4)
  1. [§3 Discussion / §4 Conclusions / Table 1] The conclusion that oPs lifetime imaging is feasible 'with respect to ... activity concentration' is not supported by the data. The phantom activities in Table 1 (1.12–1.44 MBq in ~4.5–5.5 ml, ≈232 kBq/ml) are a factor of 3–20 higher than the 10–70 kBq/ml reported for differentiated thyroid cancer metastases in Ref. [45], which the Discussion itself cites as the clinically expected range. Since the number of 3γ events per voxel scales linearly with activity concentration, a 15-min acquisition at 10 kBq/ml would have roughly an order of magnitude fewer counts per voxel than the present data, and even at 70 kBq/ml about 3× fewer. At the current 4-mm voxel level the relative uncertainty is already ~10%; scaling by the square root of counts implies ~18–45% relative errors at clinical concentrations, with many voxels failing the 20% background-error inclusion criterion. No measurement, subsampling, or simulation at 10–70 kBq/ml is presented, so the activity-concentration clause of the central claim is not demonstrated.
  2. [§1 Materials and methods / §3 Discussion] The effective spatial resolution of the voxel-wise oPs lifetime images is not characterized and is likely far coarser than the 4-mm voxel size. Each 3γ event is localized along the LOR solely by TOF of the two annihilation photons; with a time bin width of 133 ps, the single-event localization uncertainty is on the order of c·Δt/2 ≈ 20 mm, several times the smallest voxel. The authors acknowledge in §3 that 'the limiting factor ... is likely the localization of the 3γE with TOF' and that events from tube walls or air may be present. This implies that 4-mm voxel lifetimes are averages over a much larger effective volume and are contaminated by neighboring materials—consistent with the failure of the taped-tube setup in Fig. 6. The abstract's claim that 'even with 4.0^3 mm^3 voxels the samples are clearly distinguishable' is only demonstrated for separated tubes with large interior regions; the authors should quantify the point-spread function of the lifetime images (e.g., edge profiles across the tube boundaries) or restrict the spatial-resolution claims accordingly.
  3. [§3 Discussion / §4 Conclusions / Fig. 6] The taped-together configuration is the closest analog in this study to the arrangement of tissues in clinical imaging, and it does not work: the authors state that the slices in Fig. 6 'do not allow for a clear spatial distinction of the four tubes' and describe the smaller voxel sizes as at the 'limit' of the scanner. Yet the Conclusion states that oPs lifetime imaging is 'feasible ... under clinically viable conditions' without mentioning this failure. Since clinical imaging typically involves adjacent structures with different lifetime properties, the feasibility claim should be qualified, or the method should be demonstrated in at least one geometry with adjacent regions of distinct lifetimes (e.g., larger voxels, longer acquisition, or post-reconstruction processing) before the general clinical-feasibility conclusion is drawn.
  4. [Table 2 / §2 Results] The voxel-level precision reported in Table 2 does not support the assertion that the four samples are 'clearly distinguishable' at 4-mm voxel size. The single-voxel fits have uncertainties of 0.12–0.23 ns; the differences between T1 and T2 (2.56 vs 2.37 ns) and between T2 and T3 (2.37 vs 2.30 ns) are smaller than the combined uncertainties, so these pairs are not significantly separated. Only the extremes (T1 vs T4) differ by more than approximately two standard deviations. To substantiate a voxel-wise distinguishability claim, the authors should report the distribution of τ3 across voxels within each tube (e.g., mean and standard deviation over many voxels), perform pairwise statistical comparisons, or show error maps rather than a single central voxel and qualitative gray-scale images.
minor comments (6)
  1. [Abstract and §4] The sentence 'a central voxels have good count statistics' should read 'central voxels have good count statistics'.
  2. [Table 1 and §1] 'Deminalized water' in Table 1 should be 'Demineralized water'; also, the text in §1 refers to adding gelatine to 'T2', whereas Table 1 identifies the gelatine sample as T3.
  3. [§1 Materials and methods] The voxel inclusion criterion ('relative error in the background region of less than 20%') is not defined; please specify how this relative error is computed and over which region.
  4. [Eq. (1)] The prior for τ3 is informative (N(1.78 ns, 0.8 ns)) and all fitted voxel lifetimes lie within ~1σ of this prior; a sensitivity analysis with a broader or flat prior would help confirm that the voxel-level differences are data-driven rather than prior-dominated.
  5. [§1 Materials and methods] The number of 3γ events per voxel for each voxel size and acquisition is not reported; count maps would aid the reader in assessing the statistical reliability of the voxel fits.
  6. [§1 Materials and methods] The fixed values τ1=125 ps and τ2=388 ps should be justified with a reference, as these parameters may vary with material and could bias the fitted τ3 in voxels where the direct-annihilation fraction is large.

Circularity Check

0 steps flagged · score 0.0 of 10

No significant circularity: the reported oPs lifetimes are fit from measured TDDs and are not predetermined by the Bayesian priors or by the cited methodology.

full rationale

The central quantities (tau3 in whole tubes and voxels) are obtained by fitting measured time-difference distributions with a three-lifetime Gaussian-convolved model (Sec. 1, Eq. 1). The informative prior tau3 ~ N(1.78 ns, 0.8 ns) is broad enough that it does not by itself produce the observed spread (2.52, 2.37, 2.27, 1.82 ns; Tab. 2); if the fits were prior-dominated, all estimates would collapse toward 1.78 ns with roughly 0.8 ns posterior width, whereas the reported posterior uncertainties are 0.02-0.04 ns. The self-citations to Refs. [24,25] supply the fitting procedure and singles-mode event sorting, but they are not used as evidence for the measured lifetimes; the phantom data are presented and the evaluated data are deposited on Zenodo. The Discussion's admission that the 232 kBq/ml activity concentration "is still somewhat higher than one could expect in a thyroid cancer patient" (with Ref. [45] reporting 10-70 kBq/ml in metastases) is a limitation regarding the clinical-concentration clause of the conclusion, and the TOF localization of 3-gamma events is acknowledged as a limiting factor; both are external-validity or overclaim concerns, not circularity. No step in the derivation is equivalent to its inputs by construction, and no fitted parameter is renamed as a prediction.

Assumptions & free parameters 8 free parameters · 6 assumptions · 0 invented entities

The central claim depends on the Bayesian fitting model imported from the authors' prior work, hand-chosen priors and thresholds, and several domain assumptions about event selection, TOF localization, background constancy, and sample homogeneity. No new physical entities are introduced. The most fragile assumptions are TOF localization accuracy and the extrapolation from phantom activity to clinical activity.

free parameters (8)
  • Prior mean for tau3 = 1.78 ns (prior N(1.78 ns, 0.8 ns))
    Bayesian prior chosen by hand in Eq. (1); posterior for water T4 ends near this value (1.82 +- 0.02 ns), so the prior may exert influence on the absolute lifetime scale.
  • Dirichlet prior hyperparameters for branching ratios = (0.75, 3.1, 1.15)
    Chosen in Eq. (1); shape the posterior of BR1,2,3 and, through the model, the oPs component amplitude.
  • Timing resolution prior sigma = N(0.1 ns, 0.05 ns)
    Chosen in Eq. (1); the Gaussian convolution width in the fit model.
  • Time offset prior Delta = N(0 ns, 0.5 ns)
    Chosen in Eq. (1).
  • Normalization prior N = N(A, 0.1 A)
    Chosen in Eq. (1), where A is the background-subtracted integral of the data; links count scale to data.
  • Background estimation window = t < -2.5 ns
    Chosen by hand; background count fixed as mean of time differences below -2.5 ns.
  • Fit time range = -2 ns to 8 ns
    Chosen by hand for TDD fitting.
  • Voxel quality cutoff = relative background error < 20%
    Chosen by hand; only voxels passing this threshold are shown and analyzed.
assumptions (6)
  • standard math Convolution of a Gaussian with three exponential decay components models the measured time-difference distribution.
    Invoked in Methods when defining the fitting model; standard for lifetime spectroscopy.
  • domain assumption The three-photon event selection (two photons in 460 to 545 keV, one in 568 to 639 keV) isolates ortho-positronium annihilations.
    Methods section; contamination or misassignment would bias tau3.
  • domain assumption Time-of-flight localization of the two annihilation photons places each 3 gamma E event at the true annihilation position.
    Discussion admits this is a limiting factor; the voxel-wise claim depends on it.
  • domain assumption Background is constant and can be estimated from time differences below -2.5 ns.
    Methods; if background varies in time, the fixed subtraction biases fits.
  • domain assumption The four phantom samples are internally homogeneous in oPs lifetime, so spatial variation in the images is attributable to statistics and localization.
    Used to interpret image uniformity; no independent verification per voxel.
  • domain assumption Activity concentrations in the phantoms are representative enough of clinical conditions to support the feasibility conclusion.
    Discussion acknowledges phantom concentrations (about 232 kBq/ml) exceed reported thyroid-cancer uptake (10 to 70 kBq/ml); if count-rate scaling breaks this, clinical feasibility is unsupported.

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Pith. "Pith review of Positronium Lifetime Imaging with the Biograph Vision Quadra using 124I." pith.science (2026). https://pith.science/paper/YUKGXS42

@misc{pith2026250104145,
  author       = {Pith},
  title        = {Pith review of: Positronium Lifetime Imaging with the Biograph Vision Quadra using 124I},
  year         = {2026},
  howpublished = {\url{https://pith.science/paper/YUKGXS42}},
  note         = {Machine review of arXiv:2501.04145}
}
abstract

Purpose: Measuring the ortho-positronium (oPs) lifetime in human tissue bears the potential of adding clinically relevant information about the tissue microenvironment to conventional positron emission tomography (PET). Through phantom measurements, we investigate the voxel-wise measurement of oPs lifetime using a commercial long-axial field-of-view (LAFOV) PET scanner. Methods: We prepared four samples with mixtures of Amberlite XAD4, a porous polymeric adsorbent, and water and added between 1.12 MBq and 1.44 MBq of $^{124}$I. The samples were scanned in two different setups: once with a couple of centimeters between each sample (15 minutes scan time) and once with all samples taped together (40 minutes scan time). For each scan, we determine the oPs lifetime for the full samples and at the voxel level. The voxel sizes under consideration are $10.0^3$ mm$^3$, $7.1^3$ mm$^3$ and $4.0^3$ mm$^3$. Results: Amberlite XAD4 allows the preparation of samples with distinct oPs lifetime. Using a Bayesian fitting procedure, the oPs lifetimes in the whole samples are $2.52 \pm 0.03$ ns, $2.37\pm 0.03$ ns, $2.27\pm0.04$ ns and $1.82\pm 0.02$ ns, respectively. The voxel-wise oPs lifetime fits showed that even with $4.0^3$ mm$^3$ voxels the samples are clearly distinguishable and a central voxels have good count statistics. However, the situation with the samples close together remains challenging with respect to the spatial distinction of regions with different oPs lifetimes. Conclusion: Our study shows that positronium lifetime imaging on a commercial LAFOV PET/CT should be feasible under clinical conditions using $^{124}$I.

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Forward citations

Cited by 1 Pith paper

Reviewed papers in the Pith corpus that reference this work. Sorted by Pith novelty score. Full citation record

  1. First Positronium Lifetime Imaging with Scandium-44 on a Long Axial Field-of-view PET/CT

    physics.med-ph 2025-06 conditional novelty 5.0 of 10

    First positronium lifetime imaging with scandium-44 yields lifetimes consistent with water, but unresolved 1157 keV prompt photons degrade count statistics, making 44Sc inferior to 124I on this scanner.

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Pith tools

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