PONE-D-25-13108Development of an omnidirectional rotating Compton camera for imaging 177Lu radioactive contamination​PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Authors developed an omnidirectional rotating Compton camera that was capable of imaging low-level radioactive contamination caused by 177Lu-oxodotreotide. Novelty is proved by a attracting attention in nuclear medicine. By optimizing the crystal type and size,and optimizing the interval between crystals, the detector is able to adapt to a wide

range of environmental conditions, including observable gamma-ray energies, dose rates, and angular resolution. Monte Carlo simulations using Geant4 were conducted to optimize the configuration of the detector. Based on the results of the simulation, a prototype detector using six 3.5 cm cubic CaF2(Eu) crystals was developed for visualizing 177Lu-contaminated sites. The experimental results demonstrated that the detector could successfully visualize an unsealed 177Lu-oxodotreotide source with high sensitivity without being affected by gamma rays from 99mTc, which is also present in nuclear medicine facilities.

In my opinion text might be accepted for a publication in a Plos One journal.

Reviewer #2: The manuscript primarily discusses the research and development of an omnidirectional rotating Compton camera designed for imaging radioactive contamination from 177Lu. Monte Carlo simulations were conducted using Geant4 in a virtual setting to evaluate the detector's performance with various combinations of crystal types, sizes, and gamma-ray energies. The simulation findings indicated that a detector made of six 3.5-cubic-centimeter CaF2 crystals was the most suitable option. Following this, a prototype detector was created to visualize areas contaminated with 177Lu and 99mTc. Experimental results show that the rotating Compton camera technology excels in cost-effectiveness, sensitivity, and stability. The use of 208 keV gamma rays is ideal for imaging 177Lu, and this detector can simultaneously detect contamination from both 177Lu and 99mTc, which are frequently found in nuclear medicine facilities. This suggests its broad applicability in environmental radiation monitoring within such facilities. Its capability to quickly identify radioactive contamination could help minimize radiation exposure risks for medical staff and the public. However, prior to publication, the following issues need to be addressed:

In the course of developing the manuscript, what were the reasons for selecting the Monte Carlo simulation over alternative simulation techniques? Is the preference for this method attributable to its superior efficacy?

In the context of the Monte Carlo simulation, the selection of only three types of crystals—CsI, NaI, and CaF2—was made for specific experimental reasons, rather than an exhaustive evaluation of all available scintillator crystals. It is important to consider whether these three materials represent the optimal choices among scintillator crystals.

The manuscript indicates that the crystal size range utilized in the simulation spans from 0.5 to 4.0 cm. What rationale underpinned the selection of this specific range? What methodology was employed to ascertain this range? Furthermore, are there alternative size ranges that could potentially enhance the detector's performance?

The manuscript indicates that the detector is capable of concurrently visualizing the contamination of 177Lu and 99mTc. However, in practical applications, it is important to consider whether the simultaneous detection of these two contaminants may interfere with one another, potentially compromising the accuracy of the detection outcomes.

The manuscript discusses two methodologies for image reconstruction: the conventional technique and the image sharpening technique. In practical applications, which of these techniques is more prevalent? Which technique demonstrates greater utility? Additionally, have you contemplated the possibility of integrating these two approaches?

In the course of this research, what measures were implemented to ensure the accuracy and reliability of the experimental data? Were multiple repetitions of the experiments performed to mitigate potential errors? If so, what was the minimum error observed across these experiments?

The findings presented in the manuscript indicate that this detector has the potential to mitigate radiation exposure risks for both medical personnel and the general public. Consequently, what are the recommended protocols for the application of this detector in practical settings to effectively minimize these risks?

The manuscript does not provide an analysis of the detector's performance following extended usage. Could you clarify whether the detector's performance is expected to deteriorate over prolonged periods of use?

Reviewer #3: This manuscript presents the development of an omnidirectional rotating Compton camera designed to visualize low-level radioactive contamination caused by ¹⁷⁷Lu-oxodotreotide in nuclear medicine facilities. The study combines Monte Carlo simulations (Geant4) with experimental validation to optimize detector configuration, focusing on crystal type, size, and rotational mechanics. The proposed detector demonstrates promising capabilities in selectively imaging ¹⁷⁷Lu contamination while suppressing interference from 99m Tc, addressing a critical need for efficient radiation monitoring in clinical settings. The experimental methodology is comprehensive, covering simulations, prototype development, and performance tests under realistic conditions. However, while the study convincingly demonstrates feasibility, several aspects require further clarification or validation to strengthen scientific rigor and practical applicability.

(a) The Geant4 simulation employs the FTFP-BERT physics list. Why was this specific model chosen for low-energy gamma-ray interactions (e.g., 113–208 keV)? Are there validated benchmarks for

(b) ¹⁷⁷Lu gamma-ray transport in CaF2 crystals?

(c) The energy resolution formula σ(E)=0.5746E^0.5736 is adopted from a prior CsI(Tl) study. How does this generalize to CaF2 (Eu), given differences in light yield and decay time (Table 2)? Provide experimental calibration data for the CaF2-PMT system.

(d) The discrepancy between simulated and measured detection efficiency (0.50 vs. 0.30 cps/MBq) is attributed to self-absorption in the vial. Include a Monte Carlo sub-study quantifying self-absorption effects for ¹⁷⁷Lu in glass/liquid media to validate this claim.

(e) For simultaneous 177177Lu and 99m99mTc detection, the 113 keV and 141 keV peaks overlap. The 141 keV window is adjusted asymmetrically (-σ to +2σ). Provide a quantitative analysis of cross-contamination risks and how this adjustment minimizes false positives.

(f) The sensitivity drops sharply at ±60° elevation due to PMT shielding (Fig. 7). How does this angular dependency impact practical deployment in rooms with complex geometries (e.g., ceilings, floors)? Suggest design modifications to mitigate this limitation.

(g) The study mentions future work on maximum likelihood expectation maximization (MLEM). Why was filtered back-projection prioritized here? Include preliminary comparisons between the two methods to justify the current approach.

(h) Angular resolution and CNR values (e.g., σ = 12°, CNR = 28) are derived from 60-minute measurements. How do these metrics scale with shorter acquisition times (e.g., 1–10 minutes)? Provide error bars or confidence intervals for key parameters.

(i) Reducing crystal spacing from 10 cm to 7 cm reportedly doubles sensitivity but degrades angular resolution. Present a systematic trade-off analysis (sensitivity vs. resolution) to guide end-users in customizing the detector for specific applications.

(j) The compact metal-packaged PMTs introduce directional shielding. Quantify the gamma-ray attenuation caused by PMT materials (e.g., aluminum housing) using simulations or experimental measurements.

(k) The prototype weighs 7.2 kg (excluding battery). Discuss its portability in real-world scenarios (e.g., handheld operation, mounting on robotic platforms). Include data on vibration resistance or thermal stability during rotation.

(l) How does the detector’s performance compare to commercial survey meters or other Compton cameras (e.g., Polaris-H, Si/CdTe-based systems) in terms of sensitivity, angular resolution, and operational speed?

(m) The detector is proposed for high-dose environments (e.g., Fukushima). Has the radiation tolerance of CaF22(Eu) crystals and PMTs been tested under prolonged exposure (e.g., 1–10 mSv/h)?

(n) The study claims semiquantitative estimation using peak values and absolute sensitivity. Clarify the mathematical framework for converting reconstructed intensity to activity (Bq) and validate it with multi-distance measurements.

(o) The rotational motion "virtually" increases crystal count. Provide a mathematical proof or simulation demonstrating how rotation suppresses ghost artifacts across varying source geometries (e.g., multiple distributed sources).

(p) The two-step imaging strategy (conventional → sharpening) is proposed for contamination removal. How would this workflow integrate with existing radiation safety protocols (e.g., ALARA principles)? Include a case study or pilot deployment plan.

(q) The detector’s sensitivity drops above 300 keV for CaF22(Eu) (Fig. 6). For broader applicability, discuss hybrid crystal configurations (e.g., CaF22 + CsI) and provide preliminary simulation results.

(r) While ethical approval was deemed unnecessary, describe measures taken to ensure operator safety during experiments with unsealed 177177Lu sources (e.g., contamination control, dosimetry monitoring).

Reviewer #4: In this article, Tsukamoto et al. describes the development and performance of a Compton camera that is capable of detecting radiation from different directions (omnidirectional) to achieve position-sensitive detection (imaging) of the source of radiation. The Compton camera assembly consists of six scintillator crystal cubes, each mounted on a photomultiplier tube, with three facing upwards and three facing downward relative to an xy plane, to achieve bidirectional detection capabilities. The type and size of the crystal scintillators as well as the number and geometric arrangement of these detector elements in an array was optimized using Monte Carlo computer simulations. The authors also simulated the image reconstruction capabilities of this camera and the predicted sensitivity of each crystal type for different simulated gamma ray energies. When also considering cost and portability, the simulation results led to choosing europium-doped calcium fluoride crystal cubes of 3.5x3.5x3.5 cm, with six of these placed in an octahedral orientation. The authors next constructed a prototype based on the simulation results, mounting six 3.5 cm CaF2(Eu) crystals into the optimized octahedral array geometry. The entire assembly is mounted on a dual angle (azimuth and elevation) rotational stage, which achieves omnidirectionality and the ability for the Compton camera to image its surroundings. Additional post-acquisition data processing applying an image sharpening algorithm is used to reduce background noise and enhance the image quality in terms of sharpness, with a tradeoff in processing time.

This omnidirectional Compton camera prototype is demonstrated by imaging a lutetium-77 contaminated site and another site with both Lu-77 and Tc-99m, the latter being the most widely-used radioisotope currently used in medical facilities. The prototype was successfully able to locate the radioactive sources within a couple of minutes using conventional image reconstruction, and subsequently achieve higher spatial resolution in 10s of minutes once the post-processing sharpening algorithm was applied. Combined with the low cost and overall small dimensions of the device, this work effectively demonstrates the utility of the Compton camera for detecting the presence of exposed radioisotopes and pinpoint their location.

This work communicates in detail the evaluation and construction of the Compton camera, and demonstrates a working prototype that effectively images both one and two radiation sources as would be encountered in a “real world” scenario. The language is well-articulated and clear to follow the progression of thoughts from design to implementation. This paper is recommended for publication, after the authors consider some minor revisions, detailed below.

1. It is unclear if the designs for their Camera have been provided as supporting information, or the data used for their analysis been made openly available. These pieces of information are recommended prior to accepting this work for publication.

2. The europium-doped calcium fluoride crystals are sensitive to gamma radiation, however the authors also mention other radiopharmaceuticals (Table 1), two of which are not gamma emitters (yttrium-90 and strontium-89). How easy would it be to replace the scintillator crystal with one that would detect the beta radiation from these radioisotopes, and would the performance characteristics be expected to be significantly different for beta as is shown in their work for gamma? It would seem as if a scintillator that was sensitive to beta emissions would be capable of detecting/imaging more radioisotopes that are listed on Table 1 than the gamma-sensitive crystal used in this work. Please comment.

3. The authors note that the imaging performance of this camera is expected to be accurate to approximately 30 cm for a gamma source that is 1.5 meters away. Presumably, this accuracy could be improved by either moving the camera closer to the radiation source, or placing it in another location in the same room to “triangulate” the position of the radiation source. Can these points be addressed in the discussion?

4. The authors note that some amount of gamma radiation is obscured by the PMT assembly and associated electronics (line 438 and Fig 8) and suggest that the sensitivity of the detection array could be improved by bringing the scintillators closer together, at a cost of angular resolution. Could there be a way to reconfigure the placement of the scintillators “on the fly” using a mechanically-translatable assembly (such as a Hoberman-type octahedral scaffold), or would the additional mechanical braces needed for such an assembly compromise the sensitivity?

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

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Development of an omnidirectional rotating Compton camera for imaging 177Lu radioactive contamination​

PONE-D-25-13108R1

Dear Dr. Tsukamoto,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Hesham M.H. Zakaly, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #4: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #4: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #4: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #4: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #4: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors have thoroughly and successfully addressed the concerns raised in the manuscript, which now largely fulfills the criteria for publication in PLoS One. Below are the specific points that the reviewer feels require further clarification (only the aspects that the reviewer finds unclear):

This manuscript presents a formula for energy resolution utilized in the simulation process (e.g., "σ" ("E" )="0.5746E0.5736" ), derived from particular experiments. Therefore, can this formula still be used under varying experimental conditions or with different equipment? What is its range of applicability? Is there a need for recalibration or adjustment?

This manuscript discusses various factors, including self-absorption and the effects of the PMT, when examining the differences in detection efficiency. Do these factors interact with one another, resulting in a more intricate effect on detection efficiency?

This manuscript states that the detector's performance has been assessed via simulations and experiments. Nevertheless, in real-world applications, could there be variations in the performance of detectors made in different production runs? What measures can be taken to guarantee that the performance of mass-produced detectors remains consistent?

Reviewer #4: Thank you for addressing all of the concerns. The peer-review was quite intensive and the authors did an excellent job of respectfully responding to as many issues that would directly improve upon their work.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #4: No

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