A Novel Polymer-Encapsulated Multi-Imaging Modality Fiducial Marker with Positive Signal Contrast for Image-Guided Radiation Therapy
, John F. Ward 3, Stephen R. Lee 4, Falk Poenisch 5, David Michael Swanson 6, Narayan Sahoo 5, Xiaorong Ronald Zhu 5, Jingfei Ma 2, Rajat J. Kudchadker 5, Seungtaek L. Choi 7, Quynh-Nhu Nguyen 7, Lauren L. Mayo 7, Shalin J. Shah 7 and Steven J. Frank 7,*Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThis study presents an innovative fiducial marker (FM) utilized in prostate radiotherapy, subjected to testing across four imaging modalities: ultrasound (US), kilovoltage x-ray (kV), computed tomography (CT), and magnetic resonance imaging (MRI). While the research is deemed topical and groundbreaking, there are some minor concerns warranting attention.
- Title: Consider revising the title to explicitly mention the composition of the new fiducial marker.
- Introduction, L56-92: Condense the paragraphs elucidating the background and rationale of the fiducial marker.
- Introduction, L106-130: Specify the type of fiducial marker (FM) developed, particularly in relation to the metallic and non-metallic FMs mentioned earlier. In the concluding paragraph, articulate the authors' conceptualization of the novel FM based on their existing experience.
- Materials and Methods: Explore the possibility of incorporating a schematic diagram illustrating the configuration and composition of the NOVA FM.
- Materials and Methods, L211: Clarify the statement regarding kV images. Specify whether these images were acquired from the portal imagers of the proton therapy system and MV linear accelerator.
- Results, p10-12: Consider presenting the text and figures horizontally rather than vertically for enhanced clarity.
No problem.
Author Response
RESPONSE TO REVIEWER COMMENTS
We are grateful for the editors and reviewers at Cancers for their interest in our findings, their insightful comments, and their constructive suggestions. Below we provide point-by-point responses to these comments, which we have taken care to address in full. The reviewers’ comments are shown in italics.
Reviewer 1
Comments to the Author
This study presents an innovative fiducial marker (FM) utilized in prostate radiotherapy, subjected to testing across four imaging modalities: ultrasound (US), kilovoltage x-ray (kV), computed tomography (CT), and magnetic resonance imaging (MRI). While the research is deemed topical and groundbreaking, there are some minor concerns warranting attention.
Response: We agree that our findings need further validation, with additional studies of mechanisms. Such studies are underway and will be reported in future publications.
1. Title: Consider revising the title to explicitly mention the composition of the new fiducial marker.
Response: Thank you for the suggestion. The title has been changed to “A novel polymer-capsuled multi-imaging modality fiducial marker with positive signal contrast for image-guided radiation therapy”.
2. Introduction, L56-92: Condense the paragraphs elucidating the background and rationale of the fiducial marker.
Response: Thank you for the suggestion. We have condensed the paragraphs in L56-92.
3. Introduction, L106-130: Specify the type of fiducial marker (FM) developed, particularly in relation to the metallic and non-metallic FMs mentioned earlier. In the concluding paragraph, articulate the authors' conceptualization of the novel FM based on their existing experience.
Response: Thank you for raising these important points. We have added these descriptions on page 4, L126-133, and page 14, L439-441.
4. Materials and Methods: Explore the possibility of incorporating a schematic diagram illustrating the configuration and composition of the NOVA FM.
Response: Thank you for this suggestion. We added a new Supplementary Figure S1 to provide a schematic diagram illustrating the configuration and composition of the NOVA FM.
5. Materials and Methods, L211: Clarify the statement regarding kV images. Specify whether these images were acquired from the portal imagers of the proton therapy system and MV linear accelerator.
Response: Thank you for pointing this out. We have changed “The kV images were acquired…” to “The kV portal images were acquired…”.
6. Results, p10-12: Consider presenting the text and figures horizontally rather than vertically for enhanced clarity.
Response: Thank you for the great suggestion. All figures and figure legends have been presented horizontally.
We thank the reviewers and editors for their help, and we believe that their valuable feedback has substantially improved this manuscript. We hope you will find that all of the comments have been adequately addressed, and you will agree that this paper will be an important contribution to the field.
Reviewer 2 Report
Comments and Suggestions for AuthorsIn this study, a novel positive contrast multi-imaging modality fiducial marker for image-guided radiation therapy. While interesting, the following issues should be revised by revising the following issues.
1. The conclusion at lines 162-165: “FMs used in clinical practice for photon and proton radiation (e.g., Gold Anchor, BiomarC) can generate artifacts after CT image reconstruction that appear as streaks or signal voids in areas adjacent to the implanted FMs, which can reduce the accuracy o radiation treatment plans.” should be supported by the references.
2. The abbreviations of Gold Anchor, BiomarC and NOVA FMs in Figure I should be explained where they first appear in the text.
3. Can authors give an explanation of why NOVA is less perturbed than Gold and why the difference between NOVA and Carbon is less?
4. The meaning of the two figures that follow each figure in figure 4 should be explained in the notes to the figures. Besides, please attach a ruler to all images.
5. The photo layout in Figure 6 is disorganized and some of the images are not captioned in the figure notes.
6. Related paper on this topic can be cited: Preparation of Biocompatible Manganese Selenium-Based Nanoparticles with Antioxidant and Catalytic Functions, Comparison of daily megavoltage electronic portal imaging or kilovoltage imaging with marker seeds to ultrasound imaging or skin marks for prostate localization and treatment positioning in patients with prostate cancer.
Author Response
RESPONSE TO REVIEWER COMMENTS
We are grateful for the editors and reviewers at Cancers for their interest in our findings, their insightful comments, and their constructive suggestions. Below we provide point-by-point responses to these comments, which we have taken care to address in full. The reviewers’ comments are shown in italics.
Reviewer: 2
Comments to the Author
In this study, a novel positive contrast multi-imaging modality fiducial marker for image-guided radiation therapy. While interesting, the following issues should be revised by revising the following issues.
1. The conclusion at lines 162-165: “FMs used in clinical practice for photon and proton radiation (e.g., Gold Anchor, BiomarC) can generate artifacts after CT image reconstruction that appear as streaks or signal voids in areas adjacent to the implanted FMs, which can reduce the accuracy o radiation treatment plans.” should be supported by the references.
Response: Thank you for the suggestion. References have been added.
2. The abbreviations of Gold Anchor, BiomarC and NOVA FMs in Figure I should be explained where they first appear in the text.
Response: Thank you for this suggestion. The abbreviations of Gold Anchor, BiomarC and NOVA FMs have been added at the first place they appeared.
3. Can authors give an explanation of why NOVA is less perturbed than Gold and why the difference between NOVA and Carbon is less?
Response: Thank you for this observation. Unlike Gold, the NOVA markers are essentially non-metallic with a polymer capsure, thus, they have less perturbations than gold fiducial markers because higher atomic number and higher density material (gold fiducial markers) tend to perturb radiation more. The NOVA makers have more similar physical and radiological properties to the Carbon markers and thus the difference between the NOVA markers and Carbon markers is less.
4. The meaning of the two figures that follow each figure in figure 4 should be explained in the notes to the figures. Besides, please attach a ruler to all images.
Response: Thank you for this suggestion. We have added the explanation of the meaning of the two figures in the notes of the figure 4. Since for MRI, people are mostly interested in the visibility of the markers and anatomy of interests, we have added the field-of-view (FOV) in the figure legend of figure 4 to give the readers an idea of the scale of the image for MRI. Having a FOV should equivalently provide an idea of the image scale as a ruler would.
5. The photo layout in Figure 6 is disorganized and some of the images are not captioned in the figure notes.
Response: Thank you for pointing this out. To avoid confusion, we have added boarder line for each of the 6 panels (from A to F).
6. Related paper on this topic can be cited: Preparation of Biocompatible Manganese Selenium-Based Nanoparticles with Antioxidant and Catalytic Functions, Comparison of daily megavoltage electronic portal imaging or kilovoltage imaging with marker seeds to ultrasound imaging or skin marks for prostate localization and treatment positioning in patients with prostate cancer.
Response: Thank you for this suggestion. We have added this to our reference list.
We thank the reviewers and editors for their help, and we believe that their valuable feedback has substantially improved this manuscript. We hope you will find that all of the comments have been adequately addressed, and you will agree that this paper will be an important contribution to the field.
