Up-to-Date Optimization of the 90Y-PET/CT Reconstruction Protocol for Volumetric Quantification in Trans-Arterial RadioEmbolization (TARE) Procedures in the Era of Theranostics

Round 1

Reviewer 1 Report

The authors described an image reconstruction method to analyze dosimetry of Y-90 microspheres treatment of liver cancer using PET/CT in the clinical setting. The findings are of great importance because the Y-90 microsphere treatment can be greatly improved with a suitable non-invasive dosimetry method. A minor recommendation is to include a processed PET imaging of the phantoms to appeal to a larger audience. 

Author Response

Reviewer: The authors described an image reconstruction method to analyze dosimetry of Y-90 microspheres treatment of liver cancer using PET/CT in the clinical setting. The findings are of great importance because the Y-90 microsphere treatment can be greatly improved with a suitable non-invasive dosimetry method. A minor recommendation is to include a processed PET imaging of the phantoms to appeal to a larger audience. 

Answer: Thanks for your comments. We have included in the manuscript a reference sequence of experimental 90Y-PET/CT and mathematical uniform IEC NEMA Torso phantoms and IEC NEMA phantoms images used for the dosimetric approach in the gaussian filter analysis. The manuscript has been edited accordingly. Please see the attachment where the new version of the manuscript has been modified based on the reviewers' suggestions.

Author Response File: Author Response.docx

Reviewer 2 Report

This paper talk about a mCT PET-CT scanner and how it allow to perform volumetric dosimetry based on 90Y-activity distribution. The aim was an evaluation of the optimal 90Y-PET-CT reconstruction parameters based on phantoms (uniform, with sphere or semi-anthropomorphic). Major parameters as matrix size, number of iterations and gaussian filter were evaluated through recovery coefficient, coefficient of variation, root mean square error, FWHM in DVH. The results and discussion show optimal parameter as matrix of 256x256, EI of 21 and GF of 6 mm. But for smaller lesion inferior of the scanner resolution some adjustments should be performed.

This paper is very interesting and in the best way for an evaluation for PET-CT parameters for Y90-PET-CT reconstruction parameters for volumetric quantification in TARE procedures. 

The combination and modifications between the major parameters (Matrix, GF and EI) and the dosimetric consequence are the best way to understand and choice the optimal parameters of the Y90 PET-CT image.

But there is two point to consider :

- this work should be improved if we study small lesions (< scanner resolution),

- the study is made on phantoms and not an patients. 

I will finish by saying that the results of optimization of the parameters studied will have to be reviewed for the latest generation of digital PET-CT. And it will also be important to introduce the consequences of the respiratory movements on the dosimetry, but that is another subject.

Congratulations for this very nice article.

Author Response

Reviewer: This paper is very interesting and in the best way for an evaluation for PET-CT parameters for Y90-PET-CT reconstruction parameters for volumetric quantification in TARE procedures. 

The combination and modifications between the major parameters (Matrix, GF and EI) and the dosimetric consequence are the best way to understand and choice the optimal parameters of the Y90 PET-CT image.

But there is two point to consider :

- this work should be improved if we study small lesions (< scanner resolution),

- the study is made on phantoms and not an patients. 

I will finish by saying that the results of optimization of the parameters studied will have to be reviewed for the latest generation of digital PET-CT. And it will also be important to introduce the consequences of the respiratory movements on the dosimetry, but that is another subject.

Answer: Thanks for you comments. As you suggest, we provided to further underline the limitation of the study regarding small lesions and patient-based evaluations. These points will be objective of future studies in which also the latest generation of digital PET-CT will be included. Moreover, in the manuscript we provided to add, in the discussion section, the results of the study developed by Kunnen et. Al in which the new digital Siemens PET/CT “Biograph Vision” was compared with our previous model “Biograph mCT”.

We have added in the manuscript the following sentence: 

In this condition is not possible to use the FWHM metric and more studies should be conducted in this way to establish a cut off value that would represent the real limit of this new metric … especially when the volumes of interest are close to scanner spatial resolution. Evaluation of the possibility to introduce a new metric should also be considered.

Also in this aspect, more studies should be conducted to establish an objective guideline to follow in all situations … these future studies should be based firstly on phantoms and subsequently validated on patients.

Surely, the higher effective sensitivity of new digital PET/CT scanners could particularly improve 90Y-PET-CT imaging. In this sense, a study has been performed by Kunnen et. al (29) by comparing the new digital Siemens PET-CT “Biograph Vision” with its predecessor “Biograph mCT”. The results of this first study shows that new digital scanner outperforms the mCT because of its lower noise level, but based on quantitative measurements, both scanners perform similarly. This suggests that a smooth upgrade during quantitative studies is possible, if the proper reconstruction protocol is chosen.

(29) Kunnen, B., Beijst, C., Lam, M.G.E.H. et al. Comparison of the Biograph Vision and Biograph mCT for quantitative 90Y PET/CT imaging for radioembolisation. EJNMMI Phys 7, 14 (2020). https://doi.org/10.1186/s40658-020-0283-6

Please see the attachment where the new version of the manuscript has been modified based on the reviewers' suggestions.

Author Response File: Author Response.docx