The Combination of Presurgical Cortical Gray Matter Volumetry and Cerebral Perfusion Improves the Efficacy of Predicting Postoperative Cognitive Impairment of Elderly Patients

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This study investigated morphometric and perfusion brain findings in patients undergoing abdominal surgery comparing those presenting with and without post-surgery cognitive dysfunction (POCD).

The study is interesting, even though the sample size is relatively small (at least regarding POCD patients) and the scanner is suboptimal (1.5T) especially for investigating brain perfusion.

Some secondary data need to be corrected.

 

Sequences

3D T1-weighted sequence:

delete “no gaps” and “contiguous slices”, it is repetitive and obvious in a 3D

correct data about FOV, matrix and voxel size (FOV 240, matrix 256, then voxel size cannot be 1x1x1mm).

 

3D-pCASL

delete “no gaps” and “contiguous slices”, it is repetitive and obvious in a 3D

correct data about FOV, matrix and voxel size

Did you adapt post-labeling delay according to the patient’s age?

 

“Analy” should be Analysis

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This is an interesting research article about the combined use of cortical volumetry and perfusion images, both based on MRI sequences, and its association with postsurgical cognitive outcomes in elderly patients.

The introduction section defines Postoperative Cognitive Dysfunction (POCD), describes perfusion analysis and cortical volumetry in appropriate brain MRI images, setting in this way the background of this study.

Materials and methods section is well written and descriptive enough. It refers to the population of the study, the processes, neuropsychological assessment, MRI scan and analysis and statistical analyses that were implemented during this study.

The results are very interesting and well depicted in figures and tables. However, they must be critically seen, due to the small sample of the study.

In discussion, authors attempt to summarize their findings and compare them with relative literature data. They also mention the main limitation of their study.

The conclusions could be enriched by the author, with some suggestions for potential future studies.

Comments on the Quality of English Language

English language and style are generally good. Only minor issues need to be addressed before publication (e.g. in line 218, statistical analysis instead of statistical analy)

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

In this manuscript, Wang et al. utilized a combination of the cortical gray matter volume and the cerebral perfusion, which were both derived from the presurgical MRI images, to predict postoperative cognitive impairment (POCD) in elderly patients. There are some flaws in the research methods and the presentation of the results that hinder the soundness of the scientific value of this manuscript.

1. The authors didn't justify the purpose of using presurgical MRI images rather than post-surgical MRI images, or both. One possible reasoning of using presurgical imaging data is to provide a pre-diagnostic detection tool for POCD, but how can this pre-diagnostic method be differentiable between POCD and other cognitive impairment diseases, such as Alzheimer's and Parkinson's? On a related note, how does the surgery usually affect the morphology or the physiology of the brain of these elderly patients? Is anesthesia the key factor here or is there any other complications? This part can be discussed in the introduction section, which outlines the motivation of the study design.

2. The authors only provided a brief overview of POCD diagnosis. What are the current neuropsychological tests, what are the diagnoses level, and what are previous studies that demonstrate the epidemiological analysis of POCD? Were there any neuroimaging studies around POCD and what were the findings and limitations? Please add more literature review and references in the introduction section. Other than that, the authors didn't justify why a 20% reduction in a cognitive test score leads to the criteria of cognitive decline other than a referenced paper, which was published almost 19 years ago. Was there a guideline for the number 20, is it related to the time interval between two cognitive evaluations? Was there a more recent guide for the diagnosis? What was the scale of each cognitive test used in this manuscript and what does 20% reduction mean for each of the test?

3. To establish a pre-diagnosis or diagnosis, or prediction of POCD, a causal inference should be validated. However, this manuscript failed to address the causality of this association, i.e., even though the reduced cerebral prefusion and the increased gray matter volume were found in POCD patients, it's not clear that if this is solely due to POCD. As the reviewer mentioned before this is largely due to the one time point (presurgical) MRI imaging. If a post-operative MRI imaging can be acquired for each participant, each MRI scan can be normalized to its presurgical baseline, and the effect of the operation can therefore be decoupled from other confounding factors. Even though the authors addressed some of the demographic factors, such as education and sex, the causal relationship is missing in this manuscript and undermines the value of the findings. Brain anatomy varies for everyone; thus it is possible that the radiological difference the authors reported was inherently merely the anatomical difference between two sets of participants. It is impossible to go back and re-do the imaging for such a cohort study, but the authors can discuss the limitations and the implications for future studies in the discussion section.

Comments on the Quality of English Language

A number of typos were found throughout the manuscript. Some paragraphs of this manuscript need to be re-edited.

1. Line 44, "a lot of problem..." should be "a lot of problems"

2. Line 71, "Because of small sample..." would be more clear if use "Because of the small sample size"

3. Line 218, "Statistical Analysis"

4. Line 234 - 242, this paragraph is missing the subject

5. In all tables, please superscript "a", "b" and "c" as well as symbols such as ponds and asterisks

6. Line 271-277, this paragraph is ambiguous and wordy. Please re-phrase and specify if the score is presurgical or postsurgical.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

The abstract is well-structured and provides a clear overview of the study's objectives, methods, results, and conclusions. However, it could benefit from a more concise presentation. The abstract currently exceeds a typical length and includes details that might be better suited for the main text. Consider simplifying some parts, especially in the results section, to make it more reader-friendly.

The introduction provides a comprehensive background on Postoperative Cognitive Dysfunction (POCD) and the current challenges in its prediction. The mention of previous studies on gray matter volume and cerebral blood flow is appropriate, but the introduction could benefit from a more detailed exploration of existing literature that specifically addresses the limitations of these methods when used independently. Additionally, expanding the discussion on the significance of using a combined approach would provide better context for the study’s hypothesis.

Suggestions: 

• Expand the literature review to include more studies on the prediction of POCD using neuroimaging techniques.
• Highlight the gaps in the current research that this study aims to fill more explicitly.

The methods section is detailed and provides a thorough description of the study design, population, imaging techniques, and statistical analyses. The workflow diagrams included are helpful in understanding the study processes. However, some areas require clarification or further justification.

 

• The use of both ASL-MRI and high-resolution T1-weighted imaging is a significant strength of the study.
• The statistical methods are appropriate, with clear explanations of the voxel-based and surface-based analyses.

Areas for Improvement:

• The inclusion criteria are well-defined, but the exclusion criteria could benefit from a more detailed explanation of why certain conditions were chosen for exclusion. For example, the rationale for excluding patients with severe depression or anxiety could be expanded.
• The justification for the selection of specific cognitive tests and how they relate to the neuroanatomical regions of interest could be better articulated.

The results section is comprehensive, providing detailed findings from the voxel-based and surface-based analyses. The use of figures to represent the differences in cerebral blood flow and cortical gray matter volume between POCD and NPOCD patients is effective. However, the presentation of the data could be streamlined.

• Areas for Improvement:

• The presentation of demographic data in Table 1 could be enhanced by providing more context or commentary on how these variables might influence the results.
• In Table 2, while the cognitive function tests are summarized, the discussion could benefit from an explanation of the clinical significance of these differences.

5. Discussion

The discussion section effectively interprets the results in the context of existing literature. The authors provide a clear rationale for the observed differences in cerebral blood flow and gray matter volume between POCD and NPOCD patients. The discussion on the potential compensatory mechanisms in the ACC is particularly insightful.

 

• The discussion could be strengthened by providing more specific recommendations for clinical practice based on the findings. For example, how might the combined imaging approach be implemented in preoperative assessments?
• Consider addressing potential confounding factors more thoroughly, especially regarding the influence of variables such as educational level and physical activity.

6. Limitations

The limitations of the study are appropriately acknowledged. The authors mention the small sample size, the single-center design, and the potential for variability due to the use of different MRI scanners. However, the limitations section could be expanded to discuss the potential impact of unmeasured confounding variables, such as medication use or intraoperative factors.

Recommendations:

• Discuss the potential impact of unmeasured confounding variables on the results.
• Suggest ways to mitigate these limitations in future research.

The conclusion is clear and supported by the data presented. The study successfully demonstrates that the combination of cortical gray matter volumetry and cerebral perfusion improves the prediction of POCD in elderly patients. However, the conclusion could be strengthened by a brief discussion of the broader implications of these findings for clinical practice.

Recommendations:

• Provide a brief discussion on how these findings could influence clinical decision-making in the preoperative assessment of elderly patients.

Figures and Tables

The figures and tables are generally clear and well-labeled, but the resolution of some images, particularly the MRI scans, could be improved for better visualization. Additionally, the legends could provide more detailed explanations to enhance the reader's understanding.

Recommendations:

• Ensure that all figures are high-resolution and clearly labeled.
• Consider adding more descriptive legends to the figures to guide the reader.

References

The references are current and relevant to the study. However, additional references on the management of POCD and the use of multimodal imaging in cognitive assessment could be beneficial.

Recommendations:

• Consider adding more references related to the management of POCD in interventional settings and the use of combined imaging modalities in predicting cognitive outcomes.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

The authors did a meticulous job revising the manuscript.