PONE-D-23-33712Predictors of Multiple Sclerosis Progression: A Systematic Review of Conventional Magnetic Resonance Imaging StudiesPLOS ONE

Dear Dr. Broomand,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

• REVIEWER 1: This is a review of the literature regarding the predictors of progression in multiple sclerosis (MS) patients. The authors made wide selection of the sources and found some interesting observations. However some of the results and conclusions are imprecise: the expressions like "some features of MS lesions" , "some MS lesion characteristics" or "some spinal cord markers"should be described much more precisely.
  Besides, the authors did not analyze the references regarding the use of the advanced MR techniques in MS, like: MR spectroscopy, MR diffusion, MR tensor diffusion, functional MRI), they just mentioned the advanced MR techniques n the discusssion section. This should be added.
• REVIEWER 2: Summary:
  This manuscript provides a review of 53 research works regarding the progression of multiple sclerosis. It defines three aspects of progression, i.e. progression of disease, progression of disability and cognitive decline, and then summarizes the MRI correlates.
  Comments:
  The review seems to miss important recent works. See a few examples below and the references therein:
  Branco, Dario, Beniamino di Martino, Antonio Esposito, Gioacchino Tedeschi, Simona Bonavita, and Luigi Lavorgna. “Machine Learning Techniques for Prediction of Multiple Sclerosis Progression.” Soft Computing 26, no. 22 (November 1, 2022): 12041–55. https://doi.org/10.1007/s00500-022-07503-z.
  Taloni, Alessandro, Francis Allen Farrelly, Giuseppe Pontillo, Nikolaos Petsas, Costanza Giannì, Serena Ruggieri, Maria Petracca, et al. “Evaluation of Disability Progression in Multiple Sclerosis via Magnetic-Resonance-Based Deep Learning Techniques.” International Journal of Molecular Sciences 23, no. 18 (September 13, 2022): 10651. https://doi.org/10.3390/ijms231810651.
  Storelli, Loredana, Matteo Azzimonti, Mor Gueye, Carmen Vizzino, Paolo Preziosa, Gioachino Tedeschi, Nicola De Stefano, Patrizia Pantano, Massimo Filippi, and Maria A. Rocca. “A Deep Learning Approach to Predicting Disease Progression in Multiple Sclerosis Using Magnetic Resonance Imaging.” Investigative Radiology 57, no. 7 (July 1, 2022): 423–32. https://doi.org/10.1097/RLI.0000000000000854.
  Pinto, Mauro F., Hugo Oliveira, Sónia Batista, Luís Cruz, Mafalda Pinto, Inês Correia, Pedro Martins, and César Teixeira. “Prediction of Disease Progression and Outcomes in Multiple Sclerosis with Machine Learning.” Scientific Reports 10, no. 1 (December 3, 2020): 21038. https://doi.org/10.1038/s41598-020-78212-6.
  My general impression of this survey is that it provides a "first order analysis" of the found literature, meaning that it simply lists certain aspects and results of the surveyed papers, lacking deeper comprehension of the subject.
  In the research works, this definition of "disability progression" may vary substantially. The review should elaborate on the definitions and identify the most common or robust one.
  Similar holds for "cognitive decline"; how is it defined? Since there are many cognitive tests and combinations thereof, and many aspects of cognition that can be tested; hence, the definition of cognitive decline is unlikely universal? Please elaborate on the definition and variations.
  It seems that the present survey does not consistently summarize or pool the results of the studies regarding the three outcome aspects (disability&disease progression and cognitive decline). Namely, certain results are reported in Table 1 in column "Correlations with MRI markers", however, the authors mostly reported the variables nad their interactions studied, but did not report the numerical evaluation and/or significance.
  Related to above, a table mapping the MRI measurements to the three aspects of progression, with indication of the association or even a numerical results would provide a clearer picture.
  It would be beneficial to understand from reading the review in which findings the study agree and in which they do not. This would provide an answer which findings could be generalized and which need further investigation. As it currently stands, the information seems to be partially extracted and reported, leaving it up to the reading to mentally comprehend this information and extract relevant findings, which otherwise should be the purpose of the survey.
  Please elaborate on the experimental design and statistical evaluation in the reviewed studies, indicating good practices to be followed by researches reading the review.
• Besides addressing the Reviewers comments and suggestions, please do brief on Benign and Malignant classifications of MS and their predictions of MS progression using MRI.
• REVIEWER 1: This is a review of the literature regarding the predictors of progression in multiple sclerosis (MS) patients. The authors made wide selection of the sources and found some interesting observations. However some of the results and conclusions are imprecise: the expressions like "some features of MS lesions" , "some MS lesion characteristics" or "some spinal cord markers"should be described much more precisely.
  Besides, the authors did not analyze the references regarding the use of the advanced MR techniques in MS, like: MR spectroscopy, MR diffusion, MR tensor diffusion, functional MRI), they just mentioned the advanced MR techniques n the discusssion section. This should be added.
• REVIEWER 2: Summary:
  This manuscript provides a review of 53 research works regarding the progression of multiple sclerosis. It defines three aspects of progression, i.e. progression of disease, progression of disability and cognitive decline, and then summarizes the MRI correlates.
  Comments:
  The review seems to miss important recent works. See a few examples below and the references therein:
  Branco, Dario, Beniamino di Martino, Antonio Esposito, Gioacchino Tedeschi, Simona Bonavita, and Luigi Lavorgna. “Machine Learning Techniques for Prediction of Multiple Sclerosis Progression.” Soft Computing 26, no. 22 (November 1, 2022): 12041–55. https://doi.org/10.1007/s00500-022-07503-z.
  Taloni, Alessandro, Francis Allen Farrelly, Giuseppe Pontillo, Nikolaos Petsas, Costanza Giannì, Serena Ruggieri, Maria Petracca, et al. “Evaluation of Disability Progression in Multiple Sclerosis via Magnetic-Resonance-Based Deep Learning Techniques.” International Journal of Molecular Sciences 23, no. 18 (September 13, 2022): 10651. https://doi.org/10.3390/ijms231810651.
  Storelli, Loredana, Matteo Azzimonti, Mor Gueye, Carmen Vizzino, Paolo Preziosa, Gioachino Tedeschi, Nicola De Stefano, Patrizia Pantano, Massimo Filippi, and Maria A. Rocca. “A Deep Learning Approach to Predicting Disease Progression in Multiple Sclerosis Using Magnetic Resonance Imaging.” Investigative Radiology 57, no. 7 (July 1, 2022): 423–32. https://doi.org/10.1097/RLI.0000000000000854.
  Pinto, Mauro F., Hugo Oliveira, Sónia Batista, Luís Cruz, Mafalda Pinto, Inês Correia, Pedro Martins, and César Teixeira. “Prediction of Disease Progression and Outcomes in Multiple Sclerosis with Machine Learning.” Scientific Reports 10, no. 1 (December 3, 2020): 21038. https://doi.org/10.1038/s41598-020-78212-6.
  My general impression of this survey is that it provides a "first order analysis" of the found literature, meaning that it simply lists certain aspects and results of the surveyed papers, lacking deeper comprehension of the subject.
  In the research works, this definition of "disability progression" may vary substantially. The review should elaborate on the definitions and identify the most common or robust one.
  Similar holds for "cognitive decline"; how is it defined? Since there are many cognitive tests and combinations thereof, and many aspects of cognition that can be tested; hence, the definition of cognitive decline is unlikely universal? Please elaborate on the definition and variations.
  It seems that the present survey does not consistently summarize or pool the results of the studies regarding the three outcome aspects (disability&disease progression and cognitive decline). Namely, certain results are reported in Table 1 in column "Correlations with MRI markers", however, the authors mostly reported the variables nad their interactions studied, but did not report the numerical evaluation and/or significance.
  Related to above, a table mapping the MRI measurements to the three aspects of progression, with indication of the association or even a numerical results would provide a clearer picture.
  It would be beneficial to understand from reading the review in which findings the study agree and in which they do not. This would provide an answer which findings could be generalized and which need further investigation. As it currently stands, the information seems to be partially extracted and reported, leaving it up to the reading to mentally comprehend this information and extract relevant findings, which otherwise should be the purpose of the survey.
  Please elaborate on the experimental design and statistical evaluation in the reviewed studies, indicating good practices to be followed by researches reading the review.
• Besides addressing the Reviewers comments and suggestions, please do brief on Benign and Malignant classifications of MS and their predictions of MS progression using MRI.

==============================

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Kind regards,

Asokan Govindaraj Vaithinathan

Academic Editor

PLOS ONE

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Additional Editor Comments:

• REVIEWER 1: This is a review of the literature regarding the predictors of progression in multiple sclerosis (MS) patients. The authors made wide selection of the sources and found some interesting observations. However some of the results and conclusions are imprecise: the expressions like "some features of MS lesions" , "some MS lesion characteristics" or "some spinal cord markers"should be described much more precisely.

Besides, the authors did not analyze the references regarding the use of the advanced MR techniques in MS, like: MR spectroscopy, MR diffusion, MR tensor diffusion, functional MRI), they just mentioned the advanced MR techniques n the discusssion section. This should be added.

• REVIEWER 2: Summary:

This manuscript provides a review of 53 research works regarding the progression of multiple sclerosis. It defines three aspects of progression, i.e. progression of disease, progression of disability and cognitive decline, and then summarizes the MRI correlates.

Comments:

The review seems to miss important recent works. See a few examples below and the references therein:

Branco, Dario, Beniamino di Martino, Antonio Esposito, Gioacchino Tedeschi, Simona Bonavita, and Luigi Lavorgna. “Machine Learning Techniques for Prediction of Multiple Sclerosis Progression.” Soft Computing 26, no. 22 (November 1, 2022): 12041–55. https://doi.org/10.1007/s00500-022-07503-z.

Taloni, Alessandro, Francis Allen Farrelly, Giuseppe Pontillo, Nikolaos Petsas, Costanza Giannì, Serena Ruggieri, Maria Petracca, et al. “Evaluation of Disability Progression in Multiple Sclerosis via Magnetic-Resonance-Based Deep Learning Techniques.” International Journal of Molecular Sciences 23, no. 18 (September 13, 2022): 10651. https://doi.org/10.3390/ijms231810651.

Storelli, Loredana, Matteo Azzimonti, Mor Gueye, Carmen Vizzino, Paolo Preziosa, Gioachino Tedeschi, Nicola De Stefano, Patrizia Pantano, Massimo Filippi, and Maria A. Rocca. “A Deep Learning Approach to Predicting Disease Progression in Multiple Sclerosis Using Magnetic Resonance Imaging.” Investigative Radiology 57, no. 7 (July 1, 2022): 423–32. https://doi.org/10.1097/RLI.0000000000000854.

Pinto, Mauro F., Hugo Oliveira, Sónia Batista, Luís Cruz, Mafalda Pinto, Inês Correia, Pedro Martins, and César Teixeira. “Prediction of Disease Progression and Outcomes in Multiple Sclerosis with Machine Learning.” Scientific Reports 10, no. 1 (December 3, 2020): 21038. https://doi.org/10.1038/s41598-020-78212-6.

My general impression of this survey is that it provides a "first order analysis" of the found literature, meaning that it simply lists certain aspects and results of the surveyed papers, lacking deeper comprehension of the subject.

In the research works, this definition of "disability progression" may vary substantially. The review should elaborate on the definitions and identify the most common or robust one.

Similar holds for "cognitive decline"; how is it defined? Since there are many cognitive tests and combinations thereof, and many aspects of cognition that can be tested; hence, the definition of cognitive decline is unlikely universal? Please elaborate on the definition and variations.

It seems that the present survey does not consistently summarize or pool the results of the studies regarding the three outcome aspects (disability&disease progression and cognitive decline). Namely, certain results are reported in Table 1 in column "Correlations with MRI markers", however, the authors mostly reported the variables nad their interactions studied, but did not report the numerical evaluation and/or significance.

Related to above, a table mapping the MRI measurements to the three aspects of progression, with indication of the association or even a numerical results would provide a clearer picture.

It would be beneficial to understand from reading the review in which findings the study agree and in which they do not. This would provide an answer which findings could be generalized and which need further investigation. As it currently stands, the information seems to be partially extracted and reported, leaving it up to the reading to mentally comprehend this information and extract relevant findings, which otherwise should be the purpose of the survey.

Please elaborate on the experimental design and statistical evaluation in the reviewed studies, indicating good practices to be followed by researches reading the review.

*Besides the above comments of the Reviewers, it is suggested to explain the Benign and Malignant classifications of MS, does Benign and Malignant forms of classifications have any predictability on MS progression.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

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Reviewer #1: Partly

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

Reviewer #2: No

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Reviewer #1: Yes

Reviewer #2: No

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is a review of the literature regarding the predictors of progression in multiple sclerosis (MS) patients. The authors made wide selection of the sources and found some interesting observations. However some of the results and conclusions are imprecise: the expressions like "some features of MS lesions" , "some MS lesion characteristics" or "some spinal cord markers"should be described much more precisely.

Besides, the authors did not analyze the references regarding the use of the advanced MR techniques in MS, like: MR spectroscopy, MR diffusion, MR tensor diffusion, functional MRI), they just mentioned the advanced MR techniques n the discusssion section. This should be added.

Reviewer #2: Summary:

This manuscript provides a review of 53 research works regarding the progression of multiple sclerosis. It defines three aspects of progression, i.e. progression of disease, progression of disability and cognitive decline, and then summarizes the MRI correlates.

Comments:

The review seems to miss important recent works. See a few examples below and the references therein:

Branco, Dario, Beniamino di Martino, Antonio Esposito, Gioacchino Tedeschi, Simona Bonavita, and Luigi Lavorgna. “Machine Learning Techniques for Prediction of Multiple Sclerosis Progression.” Soft Computing 26, no. 22 (November 1, 2022): 12041–55. https://doi.org/10.1007/s00500-022-07503-z.

Taloni, Alessandro, Francis Allen Farrelly, Giuseppe Pontillo, Nikolaos Petsas, Costanza Giannì, Serena Ruggieri, Maria Petracca, et al. “Evaluation of Disability Progression in Multiple Sclerosis via Magnetic-Resonance-Based Deep Learning Techniques.” International Journal of Molecular Sciences 23, no. 18 (September 13, 2022): 10651. https://doi.org/10.3390/ijms231810651.

Storelli, Loredana, Matteo Azzimonti, Mor Gueye, Carmen Vizzino, Paolo Preziosa, Gioachino Tedeschi, Nicola De Stefano, Patrizia Pantano, Massimo Filippi, and Maria A. Rocca. “A Deep Learning Approach to Predicting Disease Progression in Multiple Sclerosis Using Magnetic Resonance Imaging.” Investigative Radiology 57, no. 7 (July 1, 2022): 423–32. https://doi.org/10.1097/RLI.0000000000000854.

Pinto, Mauro F., Hugo Oliveira, Sónia Batista, Luís Cruz, Mafalda Pinto, Inês Correia, Pedro Martins, and César Teixeira. “Prediction of Disease Progression and Outcomes in Multiple Sclerosis with Machine Learning.” Scientific Reports 10, no. 1 (December 3, 2020): 21038. https://doi.org/10.1038/s41598-020-78212-6.

My general impression of this survey is that it provides a "first order analysis" of the found literature, meaning that it simply lists certain aspects and results of the surveyed papers, lacking deeper comprehension of the subject.

In the research works, this definition of "disability progression" may vary substantially. The review should elaborate on the definitions and identify the most common or robust one.

Similar holds for "cognitive decline"; how is it defined? Since there are many cognitive tests and combinations thereof, and many aspects of cognition that can be tested; hence, the definition of cognitive decline is unlikely universal? Please elaborate on the definition and variations.

It seems that the present survey does not consistently summarize or pool the results of the studies regarding the three outcome aspects (disability&disease progression and cognitive decline). Namely, certain results are reported in Table 1 in column "Correlations with MRI markers", however, the authors mostly reported the variables nad their interactions studied, but did not report the numerical evaluation and/or significance.

Related to above, a table mapping the MRI measurements to the three aspects of progression, with indication of the association or even a numerical results would provide a clearer picture.

It would be beneficial to understand from reading the review in which findings the study agree and in which they do not. This would provide an answer which findings could be generalized and which need further investigation. As it currently stands, the information seems to be partially extracted and reported, leaving it up to the reading to mentally comprehend this information and extract relevant findings, which otherwise should be the purpose of the survey.

Please elaborate on the experimental design and statistical evaluation in the reviewed studies, indicating good practices to be followed by researches reading the review.

**********

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Reviewer #1: No

Reviewer #2: Yes: Žiga Špiclin

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Predictors of Multiple Sclerosis Progression: A Systematic Review of Conventional Magnetic Resonance Imaging Studies

PONE-D-23-33712R1

Dear Dr.Nima Broomand,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Asokan Govindaraj Vaithinathan

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: