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Item Considerations and recommendations from the ISMRM diffusion study group for preclinical diffusion MRI: Part 1: In vivo small-animal imaging(Wiley, 2025) Jelescu, Ileana O.; Grussu, Francesco; Ianus, Andrada; Hansen, Brian; Barrett, Rachel L. C.; Aggarwal, Manisha; Michielse, Stijn; Nasrallah, Fatima; Syeda, Warda; Wang, Nian; Veraart, Jelle; Roebroeck, Alard; Bagdasarian, Andrew F.; Eichner, Cornelius; Sepehrband, Farshid; Zimmermann, Jan; Soustelle, Lucas; Bowman, Christien; Tendler, Benjamin C.; Hertanu, Andreea; Jeurissen, Ben; Verhoye, Marleen; Frydman, Lucio; van de Looij, Yohan; Hike, David; Dunn, Jeff F.; Miller, Karla; Landman, Bennett A.; Shemesh, Noam; Anderson, Adam; McKinnon, Emilie; Farquharson, Shawna; Dell'Acqua, Flavio; Pierpaoli, Carlo; Drobnjak, Ivana; Leemans, Alexander; Harkins, Kevin D.; Descoteaux, Maxime; Xu, Duan; Huang, Hao; Santin, Mathieu D.; Grant, Samuel C.; Obenaus, Andre; Kim, Gene S.; Wu, Dan; Le Bihan, Denis; Blackband, Stephen J.; Ciobanu, Luisa; Fieremans, Els; Bai, Ruiliang; Leergaard, Trygve B.; Zhang, Jiangyang; Dyrby, Tim B.; Johnson, G. Allan; Cohen-Adad, Julien; Budde, Matthew D.; Schilling, Kurt G.; Neurology, School of MedicineSmall-animal diffusion MRI (dMRI) has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. The steps from animal setup and monitoring, to acquisition, analysis, and interpretation are complex, with many decisions that may ultimately affect what questions can be answered using the resultant data. This work aims to present selected considerations and recommendations from the diffusion community on best practices for preclinical dMRI of in vivo animals. We describe the general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in animal species and disease models and discuss why some may be more or less appropriate for different studies. We, then, give recommendations for in vivo acquisition protocols, including decisions on hardware, animal preparation, and imaging sequences, followed by advice for data processing including preprocessing, model-fitting, and tractography. Finally, we provide an online resource that lists publicly available preclinical dMRI datasets and software packages to promote responsible and reproducible research. In each section, we attempt to provide guides and recommendations, but also highlight areas for which no guidelines exist (and why), and where future work should focus. Although we mainly cover the central nervous system (on which most preclinical dMRI studies are focused), we also provide, where possible and applicable, recommendations for other organs of interest. An overarching goal is to enhance the rigor and reproducibility of small animal dMRI acquisitions and analyses, and thereby advance biomedical knowledge.Item Considerations and recommendations from the ISMRM diffusion study group for preclinical diffusion MRI: Part 2-Ex vivo imaging: Added value and acquisition(Wiley, 2025) Schilling, Kurt G.; Grussu, Francesco; Ianus, Andrada; Hansen, Brian; Howard, Amy F. D.; Barrett, Rachel L. C.; Aggarwal, Manisha; Michielse, Stijn; Nasrallah, Fatima; Syeda, Warda; Wang, Nian; Veraart, Jelle; Roebroeck, Alard; Bagdasarian, Andrew F.; Eichner, Cornelius; Sepehrband, Farshid; Zimmermann, Jan; Soustelle, Lucas; Bowman, Christien; Tendler, Benjamin C.; Hertanu, Andreea; Jeurissen, Ben; Verhoye, Marleen; Frydman, Lucio; van de Looij, Yohan; Hike, David; Dunn, Jeff F.; Miller, Karla; Landman, Bennett A.; Shemesh, Noam; Anderson, Adam; McKinnon, Emilie; Farquharson, Shawna; Dell'Acqua, Flavio; Pierpaoli, Carlo; Drobnjak, Ivana; Leemans, Alexander; Harkins, Kevin D.; Descoteaux, Maxime; Xu, Duan; Huang, Hao; Santin, Mathieu D.; Grant, Samuel C.; Obenaus, Andre; Kim, Gene S.; Wu, Dan; Le Bihan, Denis; Blackband, Stephen J.; Ciobanu, Luisa; Fieremans, Els; Bai, Ruiliang; Leergaard, Trygve B.; Zhang, Jiangyang; Dyrby, Tim B.; Johnson, G. Allan; Cohen-Adad, Julien; Budde, Matthew D.; Jelescu, Ileana O.; Neurology, School of MedicineThe value of preclinical diffusion MRI (dMRI) is substantial. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages including higher SNR and spatial resolution compared to in vivo studies, and enabling more advanced diffusion contrasts for improved microstructure and connectivity characterization. Another major advantage of ex vivo dMRI is the direct comparison with histological data, as a crucial methodological validation. However, there are a number of considerations that must be made when performing ex vivo experiments. The steps from tissue preparation, image acquisition and processing, and interpretation of results are complex, with many decisions that not only differ dramatically from in vivo imaging of small animals, but ultimately affect what questions can be answered using the data. This work represents "Part 2" of a three-part series of recommendations and considerations for preclinical dMRI. We describe best practices for dMRI of ex vivo tissue, with a focus on the value that ex vivo imaging adds to the field of dMRI and considerations in ex vivo image acquisition. We first give general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in specimens and models and discuss why some may be more or less appropriate for different studies. We then give guidelines for ex vivo protocols, including tissue fixation, sample preparation, and MR scanning. In each section, we attempt to provide guidelines and recommendations, but also highlight areas for which no guidelines exist (and why), and where future work should lie. An overarching goal herein is to enhance the rigor and reproducibility of ex vivo dMRI acquisitions and analyses, and thereby advance biomedical knowledge.Item Considerations and recommendations from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 3-Ex vivo imaging: Data processing, comparisons with microscopy, and tractography(Wiley, 2025) Schilling, Kurt G.; Howard, Amy F. D.; Grussu, Francesco; Ianus, Andrada; Hansen, Brian; Barrett, Rachel L. C.; Aggarwal, Manisha; Michielse, Stijn; Nasrallah, Fatima; Syeda, Warda; Wang, Nian; Veraart, Jelle; Roebroeck, Alard; Bagdasarian, Andrew F.; Eichner, Cornelius; Sepehrband, Farshid; Zimmermann, Jan; Soustelle, Lucas; Bowman, Christien; Tendler, Benjamin C.; Hertanu, Andreea; Jeurissen, Ben; Verhoye, Marleen; Frydman, Lucio; van de Looij, Yohan; Hike, David; Dunn, Jeff F.; Miller, Karla; Landman, Bennett A.; Shemesh, Noam; Anderson, Adam; McKinnon, Emilie; Farquharson, Shawna; Dell'Acqua, Flavio; Pierpaoli, Carlo; Drobnjak, Ivana; Leemans, Alexander; Harkins, Kevin D.; Descoteaux, Maxime; Xu, Duan; Huang, Hao; Santin, Mathieu D.; Grant, Samuel C.; Obenaus, Andre; Kim, Gene S.; Wu, Dan; Le Bihan, Denis; Blackband, Stephen J.; Ciobanu, Luisa; Fieremans, Els; Bai, Ruiliang; Leergaard, Trygve B.; Zhang, Jiangyang; Dyrby, Tim B.; Johnson, G. Allan; Cohen-Adad, Julien; Budde, Matthew D.; Jelescu, Ileana O.; Neurology, School of MedicinePreclinical diffusion MRI (dMRI) has proven value in methods development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages that facilitate high spatial resolution and high SNR images, cutting-edge diffusion contrasts, and direct comparison with histological data as a methodological validation. However, there are a number of considerations that must be made when performing ex vivo experiments. The steps from tissue preparation, image acquisition and processing, and interpretation of results are complex, with many decisions that not only differ dramatically from in vivo imaging of small animals, but ultimately affect what questions can be answered using the data. This work concludes a three-part series of recommendations and considerations for preclinical dMRI. Herein, we describe best practices for dMRI of ex vivo tissue, with a focus on image pre-processing, data processing, and comparisons with microscopy. In each section, we attempt to provide guidelines and recommendations but also highlight areas for which no guidelines exist (and why), and where future work should lie. We end by providing guidelines on code sharing and data sharing and point toward open-source software and databases specific to small animal and ex vivo imaging.Item Hierarchical neural processing in γ oscillations for syntactic and semantic operations accounts for first- and second-language epistemology(Frontiers Media, 2024-09-23) Dekydtspotter, Laurent; Miller, A. Kate; Swanson, Kyle; Cha, Jih-Ho; Xiong, Yanyu; Ahn, Jae-Hyun; Gilbert, Jane A.; Pope, Decker; Iverson, Mike; Meinert, Kent; World Languages and Cultures, School of Liberal ArtsIntroduction: We discuss event-related power differences (ERPDs) in low- and broadband-γ oscillations as the embedded-clause edge is processed in wh-dependencies such as Which decision regarding/about him/her did Paul say that Lydie rejected without hesitation? in first (L1) and second language (L2) French speakers. Methods: The experimental conditions manipulated whether pronouns appeared in modifiers (Mods; regarding him/her) or in noun complements (Comps; about him/her) and whether they matched or mismatched a matrix-clause subject in gender. Results: Across L1 and L2 speakers, we found that anaphora-linked ERPDs for Mods vs. Comps in evoked power first arose in low γ and then in broadband γ. Referential elements first seem to be retrieved from working memory by narrowband processes in low γ and then referential identification seems to be computed in broadband-γ output. Interactions between discourse- and syntax-based referential processes for the Mods vs. Comps in these ERPDs furthermore suggest that multidomain γ-band processing enables a range of elementary operations for discourse and semantic interpretation. Discussion: We argue that a multidomain mechanism enabling operations conditioned by the syntactic and semantic nature of the elements processed interacts with local brain microcircuits representing features and feature sets that have been established in L1 or L2 acquisition, accounting for a single language epistemology across learning contexts.Item Safety and Tolerability of Whole Soybean Products: A Dose-Escalating Clinical Trial in Older Adults with Obesity(MDPI, 2023-04-16) Rebello, Candida J.; Boué, Stephen; Levy, Ronald J., Jr.; Puyau, Renée; Beyl, Robbie A.; Greenway, Frank L.; Heiman, Mark L.; Keller, Jeffrey N.; Reynolds, Charles F., III; Kirwan, John P.; Biology, School of ScienceSoybean products have nutrients, dietary fiber, and phytoalexins beneficial for cardiovascular and overall health. Despite their high consumption in Asian populations, their safety in Western diets is debated. We conducted a dose-escalating clinical trial of the safety and tolerability of soybean products in eight older adults (70-85 years) with obesity. Whole green soybean pods grown under controlled conditions were processed to flour (WGS) at the United States Department of Agriculture using common cooking techniques such as slicing and heat treatment. WGS incorporated into food products was consumed at 10 g, 20 g, and 30 g/day for one week at each dose. The gastrointestinal outcomes, clinical biomarkers, and adverse events were evaluated. We explored the stimulation of phytoalexin (glyceollin) production in live viable soybean seeds (LSS-G). We compared the compositions of WGS and LSS-G with commercial soybean flour and its fermented and enzymatically hydrolyzed forms. We found that although 30 g WSG was well-tolerated, and it made participants feel full. Our processing produced glyceollins (267 µg/g) in LSS-G. Processing soybean flour decreased the iron content, but reduced the oligosaccharides, which could attenuate flatulence. Providing soybean flour at <30 g/day may be prudent for overall health and to prevent the exclusion of other food groups and nutrients in older adults with obesity.