CT-Based Thymic Morphology as an Imaging Surrogate of Immune Ageing and Its Association with Coronary Artery Calcification—A Hypothesis-Generating Observational Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a hypothesis-generating retrospective observational study investigating the association between CT-based thymic morphology as an imaging surrogate of immune ageing and coronary artery calcification quantified by the Agatston score.  But there are several concerns

1、 VNC for Agatston scoring may underestimate calcification, though literature supports high correlation ;  why did not use the true non-contrast CT for Agatston scoring and tymic Grading?  If you have no the trus non-contrast CT data, please add intra-/inter-observer variability data for VNC Agatston scores; clarify contrast phase irrelevance for calcification only.

2、Lacking lifestyle, cardiovascular risk factors (e.g., hypertension, dyslipidemia), and metabolic data (e.g., BMI); Swedish cohort links noted but unadjusted. Age range 40–64 increases coronary risk, but no cardiovascular history reported.  This lead to the insufficient confounder control. Please describe available baseline data in Table 1 extensions (e.g., clinical indications); if unavailable, emphasize as key limitation and prioritize multivariable adjustment in future.

3、thymic morphology is structural only, without immune assays (e.g., TREC, Treg counts, or NLR/PLR [25-28]), limiting mechanistic insights.  as a retrospective study, it is limited by confounding factors and causal inference.  Please explicitly state no causal inference possible

4、low high-grades (Grade 3:10.7%, Grade 4:2.9%); Figure 3 pooling justified but power unstated. Sex differences prominent but non-interactive. please report observer agreement (κ); consider logistic regression for calcification presence.

5、Only one Spectral CT system (IQon or 7500, Philips Healthcare, Best, The Nether- 92lands) was used, the results form (IQon or 7500 ). Can thymic Grading be applied to thymus grading using data collected by other devices?

6、thymic Grading: Consensus grading by three radiologists (up to 13 years experience) on a five-point scale (Grade 0: complete fatty replacement; Grade 4: >75% residual thymic tissue). How consistent are the evaluations of the three physicians?

Author Response

Dear Reviewer 1,

Thank you for the revision. Please find the point-by-point-answers in the document provided down below. 

Kind regards

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The authors present an original paper “CT-Based Thymic Morphology as an Imaging Surrogate of Immune Ageing and Its Association with Coronary Artery Calcification - A Hypothesis-Generating Observational Study”.

This study aims to investigate the relationship between thymus involution, as a marker of immune aging, and coronary calcium, which can be considered a marker of vascular aging. In my opinion, the paper is important for both clinical practice and research because it offers a novel approach to simultaneously assess thymic status and coronary calcium. This, in turn, allows for simultaneous preliminary assessment of both the risk of immune aging and vascular events.

I have a several points that should be addressed by the authors:

1. Figure 3 shows the distribution of indicators depending on age, which is more or less 52 years old.
2. Figure 3 also shows the mean values for coronary calcification. The mean values are presented without SD or CI. Table 1 shows that the distribution of coronary calcium scores is most likely not normal and has a very wide range. In my opinion, it is incorrect to present the data as an mean in either the table or the figure. It would be correct to indicate the median and interquartile range.
3. Did the authors conduct multiple comparisons between the four categories of patients, as shown in Figure 3? Did the authors perform multiple comparisons between the four categories of patients, as shown in Figure 3? It would be important to support the results obtained by showing multiple comparisons using the Kruskal-Wallis test and subsequent pairwise testing with the appropriate p-value correction.

Author Response

Dear Reviewer 2, 

Thank you very much for revising our manuscript. Please find the point-by-point responses in the document down below.

Kind regards

Author Response File: Author Response.pdf