Pub Date : 2024-09-18DOI: 10.1101/2024.09.16.24313435
Joshua Zhu, Michela Destito, Chitanya Dhanireddy, Tommy Hager, Sajid Hossain, Saahil Chadha, Durga Sritharan, Anish Dhawan, Keervani Kandala, Christian Pedersen, Nicoletta Anzalone, Teresa Calimeri, Elena De Momi, Maria Francesca Spadea, Mariam Aboian, Sanjay Aneja
Purpose: Primary central nervous system lymphoma (PCNSL) is typically treated with chemotherapy, steroids, and/or whole brain radiotherapy (WBRT). Identifying which patients benefit from WBRT following chemotherapy, and which patients can be adequately treated with chemotherapy alone remains a persistent clinical challenge. Although WBRT is associated with improved outcomes, it also carries a risk of neuro-cognitive side effects. This study aims to refine patient phenotyping for PCNSL by leveraging deep learning (DL) extracted imaging biomarkers to enable personalized therapy. Methods: Our study included 71 patients treated at our institution between 2009-2021. The primary outcome of interest was overall survival (OS) assessed at one-year, two-year, and median cohort survival cutoffs. The DL model leveraged an 8-layer 2D convolutional neural network which analyzed individual slices of post-contrast T1-weighted pre-treatment MRI scans. Survival predictions were made using a weighted voting system related to tumor size. Model performance was assessed with accuracy, sensitivity, specificity, and F1 scores. Time-dependent AUCs were calculated and C-statistics were computed to summarize the results. Kaplan-Meier (KM) survival analysis assessed differences between low and high-risk groups and statistically evaluated using the log-rank test. External validation of our model was performed with a cohort of 40 patients from an external institution. Results: The cohort's average age was 65.6 years with an average OS of 2.80 years. The one-year, two-year, and median OS models achieved AUCs of 0.73 (95% C.I., 0.60-0.85), 0.70 (95% C.I., 0.58-0.82), and 0.73 (95% C.I., 0.58-0.82) respectively. KM survival curves showcased discrimination between low and high-risk groups in all models. External validation with our one-year model achieved AUC of 0.64 (95% C.I., 0.63-0.65) and significant risk discrimination. A sub-analysis showcased stable model performance across different tumor volumes and focality. Conclusion: DL classifiers of PCNSL MRIs can stratify patient phenotypes beyond traditional risk paradigms. Given dissensus surrounding PCNSL treatment, DL can augment risk stratification and treatment personalization, especially with regards to WBRT decision making. Keywords: PCNSL; deep learning; convolutional neural network; magnetic resonance imaging; prognosis; personalized medicine
{"title":"Deriving Imaging Biomarkers for Primary Central Nervous System Lymphoma Using Deep Learning","authors":"Joshua Zhu, Michela Destito, Chitanya Dhanireddy, Tommy Hager, Sajid Hossain, Saahil Chadha, Durga Sritharan, Anish Dhawan, Keervani Kandala, Christian Pedersen, Nicoletta Anzalone, Teresa Calimeri, Elena De Momi, Maria Francesca Spadea, Mariam Aboian, Sanjay Aneja","doi":"10.1101/2024.09.16.24313435","DOIUrl":"https://doi.org/10.1101/2024.09.16.24313435","url":null,"abstract":"<strong>Purpose</strong>: Primary central nervous system lymphoma (PCNSL) is typically treated with chemotherapy, steroids, and/or whole brain radiotherapy (WBRT). Identifying which patients benefit from WBRT following chemotherapy, and which patients can be adequately treated with chemotherapy alone remains a persistent clinical challenge. Although WBRT is associated with improved outcomes, it also carries a risk of neuro-cognitive side effects. This study aims to refine patient phenotyping for PCNSL by leveraging deep learning (DL) extracted imaging biomarkers to enable personalized therapy.\u0000<strong>Methods</strong>: Our study included 71 patients treated at our institution between 2009-2021. The primary outcome of interest was overall survival (OS) assessed at one-year, two-year, and median cohort survival cutoffs. The DL model leveraged an 8-layer 2D convolutional neural network which analyzed individual slices of post-contrast T1-weighted pre-treatment MRI scans. Survival predictions were made using a weighted voting system related to tumor size. Model performance was assessed with accuracy, sensitivity, specificity, and F1 scores. Time-dependent AUCs were calculated and C-statistics were computed to summarize the results. Kaplan-Meier (KM) survival analysis assessed differences between low and high-risk groups and statistically evaluated using the log-rank test. External validation of our model was performed with a cohort of 40 patients from an external institution. <strong>Results</strong>: The cohort's average age was 65.6 years with an average OS of 2.80 years. The one-year, two-year, and median OS models achieved AUCs of 0.73 (95% C.I., 0.60-0.85), 0.70 (95% C.I., 0.58-0.82), and 0.73 (95% C.I., 0.58-0.82) respectively. KM survival curves showcased discrimination between low and high-risk groups in all models. External validation with our one-year model achieved AUC of 0.64 (95% C.I., 0.63-0.65) and significant risk discrimination. A sub-analysis showcased stable model performance across different tumor volumes and focality.\u0000<strong>Conclusion</strong>: DL classifiers of PCNSL MRIs can stratify patient phenotypes beyond traditional risk paradigms. Given dissensus surrounding PCNSL treatment, DL can augment risk stratification and treatment personalization, especially with regards to WBRT decision making.\u0000<strong>Keywords</strong>: PCNSL; deep learning; convolutional neural network; magnetic resonance imaging; prognosis; personalized medicine","PeriodicalId":501358,"journal":{"name":"medRxiv - Radiology and Imaging","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1101/2024.09.17.24313673
Francesco Santini, Michele Giovanni Croce, Xeni Deligianni, Matteo Paoletti, Leonardo Barzaghi, Niels Bergsland, Arianna Faggioli, Giulia Manco, Chiara Bonizzoni, Ning Jin, Sabrina Ravaglia, Anna Pichiecchio
Thanks to the rapid evolution of therapeutic strategies for muscular and neuromuscular diseases, the identification of quantitative biomarkers for disease identification and monitoring has become crucial. Magnetic resonance imaging (MRI) has been playing an important role by noninvasively assessing structural and functional muscular changes. This exploratory study investigated the potential of dynamic MRI during neuromuscular electrical stimulation (NMES) to detect differences between healthy controls (HCs) and patients with metabolic and myotonic myopathies. The study included 14 HCs and 10 patients with confirmed muscular diseases. All individuals were scanned with 3T MRI with a protocol that included a multi-echo gradient echo sequence for fat fraction quantification, multi-echo spin-echo for water T2 relaxation time calculation, and 3D phase contrast sequences during NMES. The strain tensor, buildup and release rates were calculated from velocity datasets. Results showed that strain and strain buildup rate were reduced in the soleus muscle of patients compared to HCs, suggesting these parameters could serve as biomarkers of muscle dysfunction. Notably, there were no significant differences in fat fraction or water T2 measurements between patients and HCs, indicating that the observed changes reflect alterations in muscle contractile properties that are not reflected by structural changes. The findings provide preliminary evidence that dynamic muscle MRI during NMES can detect abnormalities in muscle contraction in patients with myotonia and metabolic myopathies, warranting further research with larger, more homogeneous patient cohorts.
{"title":"Dynamic MR of muscle contraction during electrical muscle stimulation as a potential diagnostic tool for neuromuscular disease","authors":"Francesco Santini, Michele Giovanni Croce, Xeni Deligianni, Matteo Paoletti, Leonardo Barzaghi, Niels Bergsland, Arianna Faggioli, Giulia Manco, Chiara Bonizzoni, Ning Jin, Sabrina Ravaglia, Anna Pichiecchio","doi":"10.1101/2024.09.17.24313673","DOIUrl":"https://doi.org/10.1101/2024.09.17.24313673","url":null,"abstract":"Thanks to the rapid evolution of therapeutic strategies for muscular and neuromuscular diseases, the identification of quantitative biomarkers for disease identification and monitoring has become crucial. Magnetic resonance imaging (MRI) has been playing an important role by noninvasively assessing structural and functional muscular changes. This exploratory study investigated the potential of dynamic MRI during neuromuscular electrical stimulation (NMES) to detect differences between healthy controls (HCs) and patients with metabolic and myotonic myopathies. The study included 14 HCs and 10 patients with confirmed muscular diseases. All individuals were scanned with 3T MRI with a protocol that included a multi-echo gradient echo sequence for fat fraction quantification, multi-echo spin-echo for water T2 relaxation time calculation, and 3D phase contrast sequences during NMES. The strain tensor, buildup and release rates were calculated from velocity datasets. Results showed that strain and strain buildup rate were reduced in the soleus muscle of patients compared to HCs, suggesting these parameters could serve as biomarkers of muscle dysfunction. Notably, there were no significant differences in fat fraction or water T2 measurements between patients and HCs, indicating that the observed changes reflect alterations in muscle contractile properties that are not reflected by structural changes. The findings provide preliminary evidence that dynamic muscle MRI during NMES can detect abnormalities in muscle contraction in patients with myotonia and metabolic myopathies, warranting further research with larger, more homogeneous patient cohorts.","PeriodicalId":501358,"journal":{"name":"medRxiv - Radiology and Imaging","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1101/2024.09.17.24313704
YUSUF AKHTAR, JAYARAM K. UDUPA, Yubing Tong, Caiyun Wu, Tiange Liu, Leihui Tong, Mahdie Hosseini, Mostafa Al-Noury, Manali Chodvadiya, Joseph M. McDonough, Oscar H. Mayer, David M. Biko, Jason B. Anari, Patrick J. Cahill, Drew A. Torigian
Purpose: In respiratory disorders such as thoracic insufficiency syndrome (TIS), the quantitative study of the regional motion of the left hemi-diaphragm (LHD) and right hemi-diaphragm (RHD) can give detailed insights into the distribution and severity of the abnormalities in individual patients. Dynamic magnetic resonance imaging (dMRI) is a preferred imaging modality for capturing dynamic images of respiration since dMRI does not involve ionizing radiation and can be obtained under free-breathing conditions. Using 4D images constructed from dMRI of sagittal locations, diaphragm segmentation is an evident step for the said quantitative analysis of LHD and RHD in these 4D images. Methods: In this paper, we segment the LHD and RHD in three steps: recognition of diaphragm, delineation of diaphragm, and separation of diaphragm along the mid-sagittal plane into LHD and RHD. The challenges involved in dMRI images are low resolution, motion blur, suboptimal contrast resolution, inconsistent meaning of gray-level intensities for the same object across multiple scans, and low signal-to-noise ratio. We have utilized deep learning (DL) concepts such as Path Aggregation Network and Dual Attention Network for the recognition step, Dense-Net and Residual-Net in an enhanced encoder-decoder architecture for the delineation step, and a combination of GoogleNet and Recurrent Neural Network for the identification of the mid-sagittal plane in the separation step. Due to the challenging images of TIS patients attributed to their highly distorted and variable anatomy of the thorax, in such images we localize the diaphragm using the auto-segmentations of the lungs and the thoraco-abdominal skin. Results: We achieved an average and SD mean-Hausdorff distance of ~3 and 3 mm for the delineation step and a positional error of ~3 and 3 mm in recognizing the mid-sagittal plane in 100 3D test images of TIS patients with a different set of ~430 3D images of TIS patients utilized for building the models for delineation, and separation. We showed that auto-segmentations of the diaphragm are indistinguishable from segmentations by experts, in images of near-normal subjects. In addition, the algorithmic identification of the mid-sagittal plane is indistinguishable from its identification by experts in images of near-normal subjects. Conclusions: Motivated by applications in surgical planning for disorders such as TIS, we have shown an auto-segmentation set-up for the diaphragm in dMRI images of TIS pediatric subjects. The results are promising, showing that our system can handle the aforesaid challenges. We intend to use the auto-segmentations of the diaphragm to create the initial ground truth (GT) for newly acquired data and then refining them, to expedite the process of creating GT for diaphragm motion analysis, and to test the efficacy of our proposed method to optimize pre-treatment planning and post-operative assessment of patients with TIS and other disorders.
{"title":"Auto-segmentation of hemi-diaphragms in free-breathing dynamic MRI of pediatric subjects with thoracic insufficiency syndrome","authors":"YUSUF AKHTAR, JAYARAM K. UDUPA, Yubing Tong, Caiyun Wu, Tiange Liu, Leihui Tong, Mahdie Hosseini, Mostafa Al-Noury, Manali Chodvadiya, Joseph M. McDonough, Oscar H. Mayer, David M. Biko, Jason B. Anari, Patrick J. Cahill, Drew A. Torigian","doi":"10.1101/2024.09.17.24313704","DOIUrl":"https://doi.org/10.1101/2024.09.17.24313704","url":null,"abstract":"Purpose: In respiratory disorders such as thoracic insufficiency syndrome (TIS), the quantitative study of the regional motion of the left hemi-diaphragm (LHD) and right hemi-diaphragm (RHD) can give detailed insights into the distribution and severity of the abnormalities in individual patients. Dynamic magnetic resonance imaging (dMRI) is a preferred imaging modality for capturing dynamic images of respiration since dMRI does not involve ionizing radiation and can be obtained under free-breathing conditions. Using 4D images constructed from dMRI of sagittal locations, diaphragm segmentation is an evident step for the said quantitative analysis of LHD and RHD in these 4D images. Methods: In this paper, we segment the LHD and RHD in three steps: recognition of diaphragm, delineation of diaphragm, and separation of diaphragm along the mid-sagittal plane into LHD and RHD. The challenges involved in dMRI images are low resolution, motion blur, suboptimal contrast resolution, inconsistent meaning of gray-level intensities for the same object across multiple scans, and low signal-to-noise ratio. We have utilized deep learning (DL) concepts such as Path Aggregation Network and Dual Attention Network for the recognition step, Dense-Net and Residual-Net in an enhanced encoder-decoder architecture for the delineation step, and a combination of GoogleNet and Recurrent Neural Network for the identification of the mid-sagittal plane in the separation step. Due to the challenging images of TIS patients attributed to their highly distorted and variable anatomy of the thorax, in such images we localize the diaphragm using the auto-segmentations of the lungs and the thoraco-abdominal skin.\u0000Results: We achieved an average and SD mean-Hausdorff distance of ~3 and 3 mm for the delineation step and a positional error of ~3 and 3 mm in recognizing the mid-sagittal plane in 100 3D test images of TIS patients with a different set of ~430 3D images of TIS patients utilized for building the models for delineation, and separation. We showed that auto-segmentations of the diaphragm are indistinguishable from segmentations by experts, in images of near-normal subjects. In addition, the algorithmic identification of the mid-sagittal plane is indistinguishable from its identification by experts in images of near-normal subjects.\u0000Conclusions: Motivated by applications in surgical planning for disorders such as TIS, we have shown an auto-segmentation set-up for the diaphragm in dMRI images of TIS pediatric subjects. The results are promising, showing that our system can handle the aforesaid challenges. We intend to use the auto-segmentations of the diaphragm to create the initial ground truth (GT) for newly acquired data and then refining them, to expedite the process of creating GT for diaphragm motion analysis, and to test the efficacy of our proposed method to optimize pre-treatment planning and post-operative assessment of patients with TIS and other disorders.","PeriodicalId":501358,"journal":{"name":"medRxiv - Radiology and Imaging","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1101/2024.09.16.24313700
Benedikt Sundermann, Reinhold Feldmann, Christian Mathys, Stefan Garde, Johanna M. H. Rau, Anke McLeod, Josef Weglage, Bettina Pfleiderer
Objective: Phenylketonuria (PKU) is an inherited disorder of amino acid metabolism. Despite early dietary treatment, cognitive functioning of patients has been reported as being inferior to healthy controls. Objective of this study was to assess functional connectivity (FC) alterations in PKU in cognition-related brain networks by resting-state functional magnetic resonance imaging. We followed a hierarchical analysis approach partially based on higher criticism (HC) statistics as previously applied in a larger sister-project in fetal alcohol syndrome. Results: After exclusions for excessive head movement, 11 female young adults with early-treated PKU (age: 27.2 +- 3.7 years) and 11 age-matched female healthy controls (age: 25.9 +- 3.8 years) were included in the analysis. We observed effects within attention networks and the default mode network, but not in fronto-parietal networks, at the HC-based intermediate analysis level. No between-network FC differences were found. In the most detailed analysis level, we could not identify single affected functional connections. Despite statistical power limitations in this small sample, findings are in line with previously reported FC alterations in PKU and the cognitive profile in young adults with PKU, particularly with the still uncertain notion that cognitive control deficits might become less pronounced when PKU patients reach adulthood.
{"title":"Exploring subthreshold functional network alterations in women with phenylketonuria by higher criticism","authors":"Benedikt Sundermann, Reinhold Feldmann, Christian Mathys, Stefan Garde, Johanna M. H. Rau, Anke McLeod, Josef Weglage, Bettina Pfleiderer","doi":"10.1101/2024.09.16.24313700","DOIUrl":"https://doi.org/10.1101/2024.09.16.24313700","url":null,"abstract":"Objective: Phenylketonuria (PKU) is an inherited disorder of amino acid metabolism. Despite early dietary treatment, cognitive functioning of patients has been reported as being inferior to healthy controls. Objective of this study was to assess functional connectivity (FC) alterations in PKU in cognition-related brain networks by resting-state functional magnetic resonance imaging. We followed a hierarchical analysis approach partially based on higher criticism (HC) statistics as previously applied in a larger sister-project in fetal alcohol syndrome. Results: After exclusions for excessive head movement, 11 female young adults with early-treated PKU (age: 27.2 +- 3.7 years) and 11 age-matched female healthy controls (age: 25.9 +- 3.8 years) were included in the analysis. We observed effects within attention networks and the default mode network, but not in fronto-parietal networks, at the HC-based intermediate analysis level. No between-network FC differences were found. In the most detailed analysis level, we could not identify single affected functional connections. Despite statistical power limitations in this small sample, findings are in line with previously reported FC alterations in PKU and the cognitive profile in young adults with PKU, particularly with the still uncertain notion that cognitive control deficits might become less pronounced when PKU patients reach adulthood.","PeriodicalId":501358,"journal":{"name":"medRxiv - Radiology and Imaging","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract This paper demonstrates that simplified Convolutional Neural Network (CNN) models can outperform traditional complex architectures, such as VGG-16, in the analysis of radiological images, particularly in datasets with fewer samples. We introduce two adopted CNN architectures, LightCnnRad and DepthNet, designed to optimize computational efficiency while maintaining high performance. These models were applied to nine radiological image datasets, both public and in-house, including MRI, CT, X-ray, and Ultrasound, to evaluate their robustness and generalizability. Our results show that these models achieve competitive accuracy with lower computational costs and resource requirements. This finding underscores the potential of streamlined models in clinical settings, offering an effective and efficient alternative for radiological image analysis. The implications for medical diagnostics are significant, suggesting that simpler, more efficient algorithms can deliver better performance, challenging the prevailing reliance on transfer learning and complex models. The complete codebase and detailed architecture of the LightCnnRad and DepthNet, along with step-by-step instructions, are accessible in our GitHub repository at https://github.com/PKhosravi-CityTech/LightCNNRad-DepthNet.
{"title":"Beyond Algorithms: The Impact of Simplified CNN Models and Multifactorial Influences on Radiological Image Analysis","authors":"Saber Mohammadi, Abhinita S. Mohanty, Shady Saikali, Doori Rose, WintPyae LynnHtaik, Raecine Greaves, Tassadit Lounes, Eshaan Haque, Aashi Hirani, Javad Zahiri, Iman Dehzangi, Vipul Patel, Pegah Khosravi","doi":"10.1101/2024.09.15.24313585","DOIUrl":"https://doi.org/10.1101/2024.09.15.24313585","url":null,"abstract":"Abstract This paper demonstrates that simplified Convolutional Neural Network (CNN) models can outperform traditional complex architectures, such as VGG-16, in the analysis of radiological images, particularly in datasets with fewer samples. We introduce two adopted CNN architectures, LightCnnRad and DepthNet, designed to optimize computational efficiency while maintaining high performance. These models were applied to nine radiological image datasets, both public and in-house, including MRI, CT, X-ray, and Ultrasound, to evaluate their robustness and generalizability. Our results show that these models achieve competitive accuracy with lower computational costs and resource requirements. This finding underscores the potential of streamlined models in clinical settings, offering an effective and efficient alternative for radiological image analysis. The implications for medical diagnostics are significant, suggesting that simpler, more efficient algorithms can deliver better performance, challenging the prevailing reliance on transfer learning and complex models. The complete codebase and detailed architecture of the LightCnnRad and DepthNet, along with step-by-step instructions, are accessible in our GitHub repository at https://github.com/PKhosravi-CityTech/LightCNNRad-DepthNet.","PeriodicalId":501358,"journal":{"name":"medRxiv - Radiology and Imaging","volume":"208 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1101/2024.09.10.24313302
Pascal Wodtke, Mary A McLean, Ines Horvat-Menih, Jonathan R Birchall, Maria J Zamora-Morales, Ashley Grimmer, Elizabeth Latimer, Marta Wylot, Rolf F Schulte, Ferdia A Gallagher