PONE-D-24-42552Algorithm for Using Dual Energy Computed Tomography to Determine Chemical Composition: A Feasibility StudyPLOS ONE

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PLOS ONE

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EDITOR AND REVIEWER REPORTS

Editor comments:

In this manuscript, Choi et al. report on the use of dual-energy computed tomography (CT) to develop an algorithm to identify the chemical constituents of an unknown material (compound or mixture) and improve the accuracy of material discrimination. Using dual energies 80/140 kVp for spectral CT scans in addition to a set of 50/80 and 80/100 keV for mono-energetic X-rays, their algorithm correctly determined the chemical constituent elements of unknown materials. Their funding was compared to the data provided by the National Institute of Standards and Technology (NIST) and displayed differences of < 0.01% for compounds and 6.02% for mixture in the case of mono-energetic X-rays, and 2.98% for compounds and 6.03% for mixtures for spectral X-rays, respectively

The research has yielded important insights that make it essential for the manuscript to be published in PlosOne. The following reasons support this recommendation:

- Firstly, the research is both original and relevant. It offers valuable information on an important step towards the development of an algorithm for the evaluation of the stopping power ratio (SPR), which is crucial for the calculation of the physical dose of particle radiation in the treatment planning system (TPS). The findings are of great importance to researchers and medical staff involved in CT information in the volume unit. The study can be of great interest if the clinical applicability is demonstrated and concrete outcomes are presented.

- Secondly, the research was conducted with a high level of scientific rigour. Both qualitative and quantitative methods were used to collect and analyze data, enhancing the reliability and validity of the findings. Geant4 results were compared to the existing NIST data base.

General comments:

1. Upon assessing the similarity level of your manuscript, it has been observed that approximately 60% of the content of the main text is derived from your paper posted in the Researchsquare repository (https://doi.org/10.21203/rs.3.rs-2593701/v1). While it is permissible to submit the manuscript to an open archive while it is under review, it is advisable to have the same manuscript submitted to PlosOne in the repository, which would result in an approximate 100% similarity with the file in the repository. This adherence to scientific publication ethics and policy aims to prevent dual submission. Should you have any reasons to disclose to the editorial board of PlosOne regarding this matter, please do so.

2. The title of the manuscript needs to be revised considering changing the expression “a feasibility study”

3. The manuscript's sections need to be renumbered, as there is no numbered section whereas the authors keep referring to sections. E.g. line 209 “mentioned in 2.2.1 and 2.2.2”

4. In addition, some grammatical and sentence structure issues should be addressed during the review process as well as subscript and superscript notations. (e.g. Line 318: “… for the* detection of COVID-19 …”; Line 324: “… regarded as* excellent.”; Line 325: “… the full doses*”

Specific comments:

Title: Need to be revised to convey the main purpose of the study

Abstract: This section is for a large readership and should be written appropriately, avoiding abbreviations not acknowledged by the general public as much as possible (SPR). Consider clearly explaining where its use is unavoidable or define it for the first occurrence, and use it thereafter.

Materials and methods:

Line 103: what do the authors mean by “…when a CT image comprising multiple voxels is applied to the algorithm”

Line 110: “Cylindrical gamma detector: radius of 0.1 mm × height of 0.1 mm ”. Is the description of the detector used in this research realistic and implemented in real experiments?

Lines 114-115: “In this study, CT images based both on full energy spectra simulations and mono-energic beams were simulated. ” How did you simulate CT images?

Figure 1 is confusing. The caption should be revised. The track in Fig. 1 (b) shows that the statistic was too low and the derived data’s uncertainties are expected to be top high. Is the position of the source in (a) the same as in (b)? In (b), the source seems to be emitting from inside the box whereas in (a), it is located at a distance of 10.5 cm.

Lines 142 - 154: the detailed description could be simplified or added as supplementary material as it does not contribute to the research's main objective.

Fig. 2. The last step “<5% difference with input attenuations � output: Final solutions” is confusing. It might lead to an infinite loop if the target of <5% is never reached. Another issue is that you have data with 6%, which questions whether the authors used this algorithm for the data presented in the paper.

Line 168: Make sure all captions appear in the manuscript in the order of their citation in the text. Fig.4 seems to be quoted whereas Fig. 3 is not yet mentioned.

Line 209: “mentioned in 2.2.1 and 2.2.2” ?

Lines 212-215: This description should be enhanced taking into account the update in Fig. 4 caption.

Lines 228-230: “In the case of body tissue materials, the fractional weight of some elements was slightly modified so that the sum of the fractional weights was 100%.” Why did the authors modify the fractional weight of some elements? What was the rationale behind the modification? This is crucial to the end users and readers of the paper.

Results:

Table 2 caption should be revised to consider the content of the table itself.

Line 274: “The reasons for this will be discussed in more detail in section 4.1.”?

Lines 334-336: What is the contribution to the scientific research presented?

Lines 338-339: “Alternatively, we can reduce the number of voxels by skipping the calculation of nearby and similar HU-valued voxels.” What is the direct consequence on the obtained results, if implemented?

Line 407: Is “three to six components” a limitation of the study? What is the rationale for setting this limit?

Conclusions:

Please, summarize the main findings of your research.

Reviewer Comments:

Reviewer 1:

General comment to the authors:

The study is well-prepared and has significant results on an important topic. But some revisions are required. The specific comments are also given in the .doc file of the manuscript as comments. It is also necessary to correct some technical mistakes in the manuscript (reference citation and full stop before reference citation).

Specific comment:

Lines 35-36: “For mono-energetic X-rays, the differences were < 0.01% for compounds and 6.02% for mixture, respectively,” I think no need «respectively» at the end of the sentence.

Line 111: Precisely, which material did the authors use to fill this box-shaped material in the GEANT4 simulation?

Lines 125-126: the author hereby stated that: “In principle, applying the algorithm for identifying chemical constituent from spectral energy, we should integrate over the complete energy spectrum”. How the energy spectrum was obtained?

Line 127: I suggest changing the word "Mono energy" in the title to "monoenergy”.

Lines 165-166: “However, the noise in the image and uncertainty in measurement, f(z) would not vanish but become close to 0” What are the underlying factors contributing to noise and uncertainty in image data?

Line 195: I suggest to change the word “Utilized” to “used”

Lines 208-209: The authors mentioned “the formulas mentioned in 2.2.1 and 2.2.2” but there are not these formulas in the whole manuscript.

I suggest to change the word "mono energies" to "monoenergies” in all the text

Lines 275-277: “It was confirmed that the %difference in the case of number of constituents was 4, 5 and 6 were 0.340 – 5.449%, 1.410 – 5.188%, and 3.693 – 6.027%, respectively” What does the author intend to convey? If possible, rephrase this sentence for more clarity.

Lines 307-308: “It is considered a useful result, but several considerations were made about the problems encountered during the performing of this study and are described below.” I suggest rephrasing this sentence to enhance the clarity and convey the intended meaning more precisely.

Line 313: I suggest to change the word “quantized” to “quantified”

Line 232: in the phrase «The algorithm was tested on five compounds that combine C, H, O elements...» which compounds? I suggest citing them.

Lines 233-234: “In the case of body tissue materials, the fractional weight of some elements was slightly modified” Which elements? I suggest to enumerate the elements

Line 390-391: The authors state that to acquire both data, 1E+08 events were used for the simulation. To confirm whether data is statistically reliable, the number of events was changed and MACs were obtained ten times for each event” Why the events number was changed? Are there some methods that explain this?

If not, how did the authors go about changing the number of events, given that they defined 108 to obtain the data?

For each event, MACs were obtained ten times. For each defined energy, there must be a MAC value. If the MAC value for an event is obtained ten times then what is the total MAC average (for energy or intensity)?

Line 457: I suggest that the authors start this by “find the space …”

Reviewer 2:

I am pleased to evaluate the manuscript titled "Algorithm for Using Dual Energy Computed Tomography to Determine Chemical Composition: A Feasibility Study." Below are my comments on this work:

The study addresses an important gap by proposing an algorithm to determine chemical composition using dual-energy CT, advancing beyond the typical use of effective atomic numbers (Zeff). This approach is potentially valuable as it could reduce uncertainty in SPR (Stopping Power Ratio) calculations, which is essential for improving dose accuracy in radiation therapy.

The authors effectively strengthen their findings by employing both NIST data and Geant4 simulations for mass attenuation coefficient (MAC) values, enhancing the reliability of the results.

The manuscript is logically structured with clear sections for the introduction, methodology, results, and conclusion. Each part is well-organized, and figures and tables, particularly those comparing simulation results with NIST data, are presented effectively.

Although the article briefly addresses the impact of noise in CT images, a more detailed discussion on this topic could strengthen the study’s applicability, as noise can affect MAC calculations and the algorithm’s accuracy in clinical settings.

The work could benefit from clearer language and an expanded discussion on noise resilience. Nevertheless, the study remains scientifically sound, with promising potential for practical application.

In summary, I recommend that the authors consider these suggestions to enhance readability, and robustness, which would make this study a more comprehensive and impactful contribution to medical physics.

[Note: HTML markup is below. Please do not edit.]

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

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

Reviewer #1: Yes

Reviewer #2: 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

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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

**********

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: PLOS ONE

Manuscript Number: PONE-D-24-42552

Full Title: Algorithm for Using Dual Energy Computed Tomography to Determine Chemical Composition: A Feasibility Study

General comment to the author’s:

The study is well-prepared and has significant results on an important topic. But some revisions are required. The specific comments are also given in the .doc file of the manuscript as comments. It is also necessary to correct some technical mistakes in the manuscript (reference citation and full stop before reference citation).

Specific comment:

Lines 35-36: “For mono-energetic X-rays, the differences were < 0.01% for compounds and 6.02% for mixture, respectively” I think no need «respectively» at the end of the sentence.

Line 111: Precisely, which material the authors are used to fill this Box shaped material in GEANT4 simulation?

Lines 125-126: the author hereby stated that: “In principle, applying the algorithm for identifying chemical constituent from spectral energy, we should integrate over the complete energy spectrum”.How the energy spectrum was obtained?

Line 127: I suggest to change the word "Mono energy" in the title to "monoenergy”.

Lines 165-166: “However, the noise in the image and uncertainty in measurement, f(z) would not vanish but become close to 0” What are the underlying factors contributing to noise and uncertainty in image data?

Line 195: I suggest to change the word “Utilized” to “used”

Lines 208-209: The authors mentioned “the formulas mentioned in 2.2.1 and 2.2.2” but there are not these formulas in all the manuscript.

I suggest to change the word "mono energies" to "monoenergies” in all the text

Lines 275-277: “It was confirmed that the %difference in the case of number of constituents was 4, 5 and 6 were 0.340 – 5.449%, 1.410 – 5.188%, and 3.693 – 6.027%, respectively” What does the author intend to convey? If possible, rephrase this sentence for more clarity.

Lines 307-308: “it is considered a useful result, but several considerations were made about the problems encountered during performing of this study and are described below.” I suggest to rephrase this sentence to enhance the clarity and convey the intended meaning more precisely.

Line 313: I suggest to change the word “quantized” to “quantified”

Line 232: in the phrase «The algorithm was tested on five compounds that combine C, H, O elements...» which compounds? I suggest to cite them.

Lines 233-234: “In the case of body tissue materials, the fractional weight of some elements was slightly modified” which elements? I suggest to enumerate the elements

Line 390-391: The authors states that to acquire both data, 1E+08 events were used for the simulation. To confirm whether data is statistically reliable, the number of events was changed and MACs was obtained ten times for each event” Why the events number was changed? There are some methods that explain this?

If not, how did the authors go about changing the number of events, given that they defined 108 to obtain the data?

For each event, MACs were obtained ten times. For each defined energy, there must be a MAC value. If the MAC value for an event is obtained ten times then total MAC is the average (for an energy or intensity)?

Line 457: I suggest that the authors start this by “find the space …”

Reviewer #2: I am pleased to evaluate the manuscript titled "Algorithm for Using Dual Energy Computed Tomography to Determine Chemical Composition: A Feasibility Study." Below are my comments on this work:

The study addresses an important gap by proposing an algorithm to determine chemical composition using dual-energy CT, advancing beyond the typical use of effective atomic number (Zeff). This approach is potentially valuable as it could reduce uncertainty in SPR (Stopping Power Ratio) calculations, which is essential for improving dose accuracy in radiation therapy.

The authors effectively strengthen their findings by employing both NIST data and Geant4 simulations for mass attenuation coefficient (MAC) values, enhancing the reliability of the results.

The manuscript is logically structured with clear sections for the introduction, methodology, results, and conclusion. Each part is well-organized, and figures and tables, particularly those comparing simulation results with NIST data, are presented effectively.

Although the article briefly addresses the impact of noise in CT images, a more detailed discussion on this topic could strengthen the study’s applicability, as noise can affect MAC calculations and the algorithm’s accuracy in clinical settings.

The work could benefit from clearer language and an expanded discussion on noise resilience. Nevertheless, the study remains scientifically sound, with promising potential for practical application.

In summary, I recommend that the authors consider these suggestions to enhance readability, robustness, which would make this study a more comprehensive and impactful contribution to medical physics.

**********

6. 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.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

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 #1: No

Reviewer #2: No

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Attachments

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Submitted filename: SPR_Manuscript_PlosOne.docx

Attachment

Submitted filename: Reviewer comment.docx

<p>Algorithm for Using Dual Energy Computed Tomography to Determine Chemical Composition: Method Development and Validation

PONE-D-24-42552R1

Dear Dr. Ahn,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Cebastien Joel Guembou Shouop, Ph.D., ME, MS

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Overall, the author did a great job in revising the manuscript.

One thing left to the author is whether the state of the five compounds tested can be generalized to other types of materials (perhaps H2O in solid (ice), liquid (water), and gas (vapor) states).

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 #1: 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 #1: Yes

**********

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

Reviewer #1: Yes

**********

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 #1: Yes

**********

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 #1: Yes

**********

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 #1: (No Response)

**********

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.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

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 #1: No

**********