Feasibility of non-contact cardiorespiratory monitoring using impulse-radio ultra-wideband radar in the neonatal intensive care unit

Won Hyuk Lee; Yonggu Lee; Jae Yoon Na; Seung Hyun Kim; Hyun Ju Lee; Young-Hyo Lim; Seok Hyun Cho; Sung Ho Cho; Hyun-Kyung Park

doi:10.1371/journal.pone.0243939

Peer Review History

Original SubmissionJuly 30, 2020
20 Aug 2020 Decision Letter - Georg M. Schmölzer, Editor PONE-D-20-21820 Feasibility of non-contact cardiorespiratory monitoring using impulse-radio ultra-wideband radar in the Neonatal Intensive Care Unit PLOS ONE Dear Dr. Hyun-Kyung Park, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by September 30 2020. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 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: No ****** 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 ****** 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: This study investigates the feasibility of non-contact cardiorespiratory monitoring using impulse-radio ultra-wideband radar in the Neonatal Intensive Care Unit by comparing the measures with conventional electrocardiography (ECG)/impedance pneumography (IPG). I have several comments and questions for Statistical analysis. Line 211, the abbreviation of SD must be defined the first time it is used. Please make it clear what is “the bias between the radar and the conventional measurements”. Does such “bias” equal to the difference between the radar and the conventional measurements? I do not see any reports in this manuscript about intra-individual variances and inter-individual variances. How would you incorporate repeated measures in one-way ANOVA? According to data shown in S1 table, in Figure 5, the titles of the two boxes should be exchanged. In figure 5, what do those vertical bars represent? One sample t-tests is not necessary because small difference from zero will get significant result when the sample size is large. To reflect the mean bias, 95% CI may be used. ****** 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 [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0243939.r001
Revision 1
30 Aug 2020 Author Response Reviewer #1: This study investigates the feasibility of non-contact cardiorespiratory monitoring using impulse-radio ultra-wideband radar in the Neonatal Intensive Care Unit by comparing the measures with conventional electrocardiography (ECG)/impedance pneumography (IPG). I have several comments and questions for Statistical analysis. 1. Line 211, the abbreviation of SD must be defined the first time it is used. : Thanks for your comment. We have defined the term of SD in Line 204 at first instead. 2. Please make it clear what is “the bias between the radar and the conventional measurements”. Does such “bias” equal to the difference between the radar and the conventional measurements? : Thanks for your detailed comment. We want to talk about the difference between the radar and the conventional measurement, so we have changed “bias” to “differences” as your comment in Line 211. 3. I do not see any reports in this manuscript about intra-individual variances and inter-individual variances. How would you incorporate repeated measures in one-way ANOVA? : Thank you for your deep interest in statistically analysis. We used CCC to check the agreement of the measurements of the IR-UWB radar sensor and conventional measurements. Various statistical methods were considered to analyze the agreement between both methods, but since one-way ANOVA was not used, the content has been removed from the manuscript. 4. According to data shown in S1 table, in Figure 5, the titles of the two boxes should be exchanged. : Thank you for your comments. As your comment, it is correct that the two boxes in Figure 5 have been exchanged. Including the comment below, we would revise Figure 5 accordingly. 5. In figure 5, what do those vertical bars represent? One sample t-tests is not necessary because small difference from zero will get significant result when the sample size is large. To reflect the mean bias, 95% CI may be used. : Thank you for your comments. Figure 5 shows the t-test results for the difference between heart rate and respiratory rate of the IR-UWB radar sensor and the conventional measurements. Vertical bar means CI, and the figure is incorrect, so we corrected the figure rightly. During the overall review of the manuscript submitted, there was a mistake in the radar device name used for data collection. We changed the product name to XK200 (Xandar Kardian, Delaware, USA) in Line 126 and Figure 1. Also, the website address related to FCC certification has expired, so we have attached a new address and revised it in Line 133. We’re sorry for such a mistake. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0243939.r002
30 Oct 2020 Decision Letter - Georg M. Schmölzer, Editor PONE-D-20-21820R1 Feasibility of non-contact cardiorespiratory monitoring using impulse-radio ultra-wideband radar in the Neonatal Intensive Care Unit PLOS ONE Dear Dr. Hyun-Kyung Park, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by December 20 2020. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Georg M. Schmölzer Academic Editor PLOS ONE [Note: HTML markup is below. Please do not edit.] 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: (No Response) ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: 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 #2: 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 #2: 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 #2: Review of: Feasibility of non-contact cardiorespiratory monitoring using impulse-radio ultrawideband radar in the Neonatal Intensive Care Unit Lee WH et al. PONE-D-20-21820R1 Lee et al report the ‘next step’ in development of a non-contact cardiorespiratory monitoring technology for heart rate and respiratory rate monitoring of newborn infants. This follows their pre-clinical report published last year (Park JY et al, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695386/ ). It is well written, and provides information on a promising technology. They do a good job in describing the limitations and next steps before this technology moves closer to clinical application. As a non-statistician, my most significant question for this or a follow-on question is how reliable, valid and accurate the new technology is relative to the gold standard when analyzing high and low Heart Rates and respiratory rates? Can alarms be triggered? Would they be triggered too often, not often enough, or at an expected rate? Other minor comments/questions follow. Introduction. The authors might want to identify citations to justify the statement: “Repetitive replacement of electrodes and the twining wires around the arm or leg cause skin damage, infections due to skin layer breakdown, permanent scars, and circulatory disturbances, particularly in premature infants with fragile skin. There may even be a risk of hypothermia during procedures, which could cause circulatory disturbances, particularly in premature infants. In addition to reference 2, the authors may want to cite a more recent reference on the impact of all the current leads in use on family interactions with their neonates (Bonner O, et al. 'There were more wires than him': the potential for wireless patient monitoring in neonatal intensive care. BMJ Innov. 2017;3(1):12-18. doi:10.1136/bmjinnov-2016-000145). METHODS Very minor, but in the location for MATLAB, the authors list the company location as “MathWorks, New York, MA, USA”). I think the headquarters of the company is Natick, MA, USA. Very minor, line 176 of the revised manuscript w/ tracked changes, one word is misspelled: “...want to increase the Frames per sencod (FPS) of the radar to increase the quality of...” should be “...want to increase the Frames per second (FPS) of the radar to increase the quality of...”. I am not that statistically savvy, but would be interested in how well the correlations hold up at the lower and upper extremes of HR and RR. Are there specific statistical tests for measurement comparisons w/ gold standard technologies that accentuate the evaluation of the extremes? Maybe something like Figure 4 with HR and RR low, high and middle rates in place of the BW groupings would give a visual representation that I’m sure a wise statistician could translate more quantitatively. DISCUSSION It’s one really good thing to pick up the normal range for HR and RR. How does the radar technology perform in picking up apnea and bradycardia? Could the authors in this (or a subsequent) paper tell the reader specifically about correlations between two techniques in alarms and abnormal readings on the low and high ends of both HR and RR? ****** 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 #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0243939.r003
Revision 2
25 Nov 2020 Author Response Review Comments to the Author Reviewer #2: Review of: Feasibility of non-contact cardiorespiratory monitoring using impulse-radio ultrawideband radar in the Neonatal Intensive Care Unit Lee WH et al. PONE-D-20-21820R1 Lee et al report the ‘next step’ in development of a non-contact cardiorespiratory monitoring technology for heart rate and respiratory rate monitoring of newborn infants. This follows their pre-clinical report published last year (Park JY et al, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695386/ ). It is well written, and provides information on a promising technology. They do a good job in describing the limitations and next steps before this technology moves closer to clinical application. As a non-statistician, my most significant question for this or a follow-on question is how reliable, valid and accurate the new technology is relative to the gold standard when analyzing high and low Heart Rates and respiratory rates? Can alarms be triggered? Would they be triggered too often, not often enough, or at an expected rate? Other minor comments/questions follow. Introduction. The authors might want to identify citations to justify the statement: “Repetitive replacement of electrodes and the twining wires around the arm or leg cause skin damage, infections due to skin layer breakdown, permanent scars, and circulatory disturbances, particularly in premature infants with fragile skin. There may even be a risk of hypothermia during procedures, which could cause circulatory disturbances, particularly in premature infants. In addition to reference 2, the authors may want to cite a more recent reference on the impact of all the current leads in use on family interactions with their neonates (Bonner O, et al. 'There were more wires than him': the potential for wireless patient monitoring in neonatal intensive care. BMJ Innov. 2017;3(1):12-18. doi:10.1136/bmjinnov-2016-000145). : Thanks for your comments. As you advised, we have added the above reference to our manuscript (Reference 9). METHODS Very minor, but in the location for MATLAB, the authors list the company location as “MathWorks, New York, MA, USA”). I think the headquarters of the company is Natick, MA, USA. : Thank you for your comments. We have modified the location of the company’s headquarter in Line 131. Very minor, line 176 of the revised manuscript w/ tracked changes, one word is misspelled: “...want to increase the Frames per sencod (FPS) of the radar to increase the quality of...” should be “...want to increase the Frames per second (FPS) of the radar to increase the quality of...”. : Thank you for your comments. The corresponding misspelled words was modified and corrected in line 178. I am not that statistically savvy, but would be interested in how well the correlations hold up at the lower and upper extremes of HR and RR. Are there specific statistical tests for measurement comparisons w/ gold standard technologies that accentuate the evaluation of the extremes? Maybe something like Figure 4 with HR and RR low, high and middle rates in place of the BW groupings would give a visual representation that I’m sure a wise statistician could translate more quantitatively. : Thank you for the comment. We have compared the bias levels among the 3 body weight groups through a graphical presentation and one sample t-test in the last manuscript. However, the more proper method to compare the bias levels among 3 groups would be one-way ANOVA (analysis of variance) with/without post-hoc tests such as Bonferroni or Tukey method. Therefore, we included the results of ANOVA tests among the 3 body weight groups in the revised manuscript (Figure 5A). In response to your comment, we think that the bias levels between the radar and the conventional methods could also be compared among categories divided using HR and RR. Lin’s concordance correlation coefficients should not be used for the comparison because there were no established methods for the correction of the range restriction problem that must follow the categorization of the variable through dividing the data range. However, comparisons of the biases between two measurements could bypass this problem. We defined HR and RR > upper 5% and < lower 5% as the extreme values and divided the measurements into 3 categories as follow; Category 1: <5%, Category 2: 5~95% and Category 3: >95%. HRs were divided at 115 and 149 bpm and RRs were divided at 25 and 67 breaths/minute. We compared the bias levels between the two measurement methods among these 3 groups for both HR and RR using graphical presentations and one-any ANOVA (Figure 5B). The biases between the two measurement methods were smaller in the category 2 (5%~95%) in both HR and RR and the radar measured HR and RR more frequently in the low HR and RR range and less frequently in the high HR and RR range. In accordance with your comment, we revised the manuscript including these analysis results as Figure 5B. DISCUSSION It’s one really good thing to pick up the normal range for HR and RR. How does the radar technology perform in picking up apnea and bradycardia? Could the authors in this (or a subsequent) paper tell the reader specifically about correlations between two techniques in alarms and abnormal readings on the low and high ends of both HR and RR? : Thank you for your comments. We are developing algorithms to detect apnea, arrhythmia and bradycardia using radar technology. However, in the NICU environment, the treatment comes first when the symptoms appear, so the low number of times apnea, arrhythmia, and bradycardia have occurred is early to verify the accuracy of detecting them. We will conduct an experiment to accurately detect and verify the accuracy of this part in further research. Plsease see attched "(2nd) Response to Reviewers" file. Attachments Attachment Submitted filename: (2nd) Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0243939.r004
1 Dec 2020 Decision Letter - Georg M. Schmölzer, Editor Feasibility of non-contact cardiorespiratory monitoring using impulse-radio ultra-wideband radar in the Neonatal Intensive Care Unit PONE-D-20-21820R2 Dear Dr. Hyun-Kyung Park, 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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, Georg M. Schmölzer Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0243939.r005
Formally Accepted
15 Dec 2020 Acceptance Letter - Georg M. Schmölzer, Editor PONE-D-20-21820R2 Feasibility of non-contact cardiorespiratory monitoring using impulse-radio ultra-wideband radar in the Neonatal Intensive Care Unit Dear Dr. Park: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Georg M. Schmölzer Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0243939.r006

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