Integrated Small Animal PET/CT/RT with Onboard PET/CT Image Guidance for Preclinical Radiation Oncology Research
Round 1
Reviewer 1 Report
Overall, it is a well-prepared paper. I have several minor suggestions.
1. Page 2, section 2.1
"with a 11.0 cm diameter animal port". It was repeated later.
"the uniform ~1.1 mm spatial resolutions were achieved with depth-of-interaction (DOI) measurable detectors within 30 mm or 20 mm FOV radius with or without the resolution recovery by applying a point spread function with ~1.0 mm full-width-half-maximum (FWHM) Gaussian." It isn't easy to understand. Please reorganize this part. Also, a reference should be added.
Page. 4 Section 2.3
"A standard method..." What does the "standard method" means? It is better to mention the method directly.
Section 2.4
Please add more information about the phantom, such as the rod size.
Page 7 Figure 5.
It is better to add the rod size to the figure.
Author Response
We thank reviewer’s comments and suggestions that improved the quality of the manuscript. The responses are highlighted in red, and the corresponding revisions in the revised manuscript are also shown below the responses.
Reviewer #1:
- Page 2, section 2.1
"with a 11.0 cm diameter animal port". It was repeated later.
- Removed the repeated information.
"the uniform ~1.1 mm spatial resolutions were achieved with depth-of-interaction (DOI) measurable detectors within 30 mm or 20 mm FOV radius with or without the resolution recovery by applying a point spread function with ~1.0 mm full-width-half-maximum (FWHM) Gaussian." It isn't easy to understand. Please reorganize this part. Also, a reference should be added.
- Revised, and a relevant reference is added.
“A ~1.1 mm uniform spatial resolutions were achieved within 20 mm FOV radius without the resolution recovery, while the same ~1.1 mm uniform spatial resolutions within 30 mm FOV radius can be achieved by including the resolution recovery with a ~1.0 mm full-width-half-maximum (FWHM) Gaussian.”
Page. 4 Section 2.3
"A standard method..." What does the "standard method" means? It is better to mention the method directly.
- Revised to “An existing method …”
Section 2.4
Please add more information about the phantom, such as the rod size.
- More phantom information was added.
“The diameter and length of the phantom insert are 26.0 and 10.0 mm. The diameters of the through holes (rods) which are arranged in six sections within the insert are 0.75, 1.0, 1.35, 1.7, 2.0, and 2.4 mm, respectively.”
Page 7 Figure 5.
It is better to add the rod size to the figure.
- Yes, rod sizes were added in the figure.
Reviewer 2 Report
Due to the interest in translational research in radiotherapy and radiobiology, the PET/CT/RT concept proposed by Chen et al. is up to date. The authors propose the integration of lightweight PET with an existing CT image-guided for small animal irradiator PET/CT image-guided preclinical radiation therapy (RT) research. The methodology and technical implementation of the trimodal hybrid car is thoroughly detailed. In an era of personalized medicine, research in radiobiology and radiomics is indispensable to the progress of radiation oncology. The only mention would be that I would add to the discussions the importance for radiomics and for the development of AI in radiation oncology of the device and the proposed concept.
The concept of "Integrated Small Animal PET/CT/RT with Onboard PET/CT Image Guidance for Preclinical Radiation Oncology Research proposed by Chen et al. addresses an innovative topic in fundamental research on small animal models in image-guided radiotherapy, the integration of functional PET imaging in a device dedicated to CT image-guided irradiation of small animals. In the context of a large-scale implementation of the precision medicine concept, radiation therapy planning including hybrid imaging is a top field of research and the subject is of maximum interest. Only a few works in the literature address this subject: I mention the work of Ghiata et al. (doi.org/10.3390/cancers11020170) and the work of Mikhaylova et al. (doi: 10.1109/access.2019.2944683.) which addresses the concept and prototype of PET/CT/RT, but also a paper by the first author that presents this concept (doi: 10.1088/1361-6560/ac2bb4.).The work is a pioneering subject in translational research in radiotherapy and will certainly contribute to the development of the method. At this point in the study, I believe that the data presented are sufficient, but until it is implemented as a standard in research. The dosimetric evaluation will have to be the next stage including some guidelines for the target volumes delineation in small animals research and the calculations of the CTV-PTV uncertainty interval depending on the possible sources of errors and uncertainties. We also consider the relevant conclusions and references for the proposed study. In the 7 figures are presented both the technical principles of PET integration in small animals CT/RT device, the positioning of the small animal for evaluation, the calibration of CT-PET for different FOVs with the help of 22 Na sources and the acquisition of trans-axial, coronal and hybrid images sagittal using [18F]FDG PET, CT, and PET/CT images, but also intensity profiles for each incidence and proposed method. I would mention as completing/improving the manuscript, the possible applications in radiomics as perspective of the future, taking into account that radiomic guided radiotherapy is certainly the great technological revolution that could impact imaging in radiotherapy.
Author Response
We thank reviewer’s comments and suggestions that improved the quality of the manuscript. The responses are highlighted in red, and the corresponding revisions in the revised manuscript are also shown below the responses.
Reviewer #2:
- Thank you for the inputs and suggestions. Although this study is instrumentation development and evaluation in nature and all authors have no research expertise in the field of radiomics, we tried to list potential applications of this newly developed preclinical PET/CT/RT for the radiomics development and applications.
“With the growing interest in preclinical PET radiomics studies, animal PET/CT/RT can provide a missing dataset of quantitative, biological image-guided radiotherapy to facilitate the radiomics analysis and modeling in preclinical studies. Additionally, it will also enable co-clinical radiomics investigations and potentially radiomic guided radiotherapy applications by comparing between the clinical radiomics analysis and the preclinical one with a known disease model, repeated, and high-precision and biologically targeted animal radiation studies.”
Reviewer 3 Report
This work integrated a small animal PET scanner to a CT/RT sytem for the first time. The paper was well written an the results were of interesting to the field. I think the paper can be accepted. I only have two minor suggestions.
1. It is better to show more detail of the PET scanner such as the number of the detectors, the arrangement of the detectors, the crystal size and SiPM array information et al, so the readers do not need to read the reference to find the PET scanner information.
2) There are some small texts in figure 7. They need to be either removed or explained.
1. What is the main question addressed by the research? This work integrated a small animal PET scanner to an existing small animal CT/RT system so PET/CT images can be used for guidance of preclinical radiation therapy.
2. Do you consider the topic original or relevant in the field, and if so, why? To my knowledge, this work is the first time that a full ring PET scanner was integrated with a CT/RT system and molecular and anatomic images with better registration used to guide radiation therapy. The paper was well written an the results were of interesting to the field.
3. What does it add to the subject area compared with other published material? Previously no similar work was published.
4. What specific improvements could the authors consider regarding the methodology? It is better to show more detail of the PET scanner such as the number of the detectors, the arrangement of the detectors, the crystal size and SiPM array information et al, so the readers do not need to read the reference to find the PET scanner information.
5. Please include any additional comments on the tables and figures. There are some small texts in figure 7. They need to be either removed or explained.
Author Response
We thank reviewer’s comments and suggestions that improved the quality of the manuscript. The responses are highlighted in red, and the corresponding revisions in the revised manuscript are also shown below the responses.
Reviewer 3:
- It is better to show more detail of the PET scanner such as the number of the detectors, the arrangement of the detectors, the crystal size and SiPM array information et al, so the readers do not need to read the reference to find the PET scanner information.
- Yes, more information related to PET scanner is added.
“The PET consists of a ring of 12 detector panels in a dodecagon configuration. Each detector panel has a 30´30 array of 1x1x20 mm3 Ce-doped Lutetium-Yttrium Oxyorthosilicate (Lu0.6Y1.4SiO0.5:Ce, LYSO) scintillators. Each end of the scintillator array is optically coupled to an 8x8 silicon photomultiplier array (model MPPC S13361-2050-08, Hamamatsu Photonics K.K.) for depth-of-interaction (DOI) measurement based on the dual-ended readout.”
2) There are some small texts in figure 7. They need to be either removed or explained.
- The meaning of those small texts embedded in the figure 7 are explained in the figure 7 caption.
“The additional numbers in the figures are the maximum and minimum intensity profile values of PET (blue) and CT (yellow) and the axis range (white).”
