Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis
Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can probe tissue biochemistry in vivo with high resolution and sensitivity without requiring exogenous contrast agents. Applying CEST MRI at ultrahigh field provides advantages of increasing spectral resolution and improvi...
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| Format: | Article |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.764690/full |
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| author | Kristin P. O'Grady Kristin P. O'Grady Sanjana Satish Quinn R. Owen Bailey A. Box Francesca Bagnato Francesca Bagnato Anna J. E. Combes Anna J. E. Combes Sarah R. Cook Holly James Westervelt Haley R. Feiler Richard D. Lawless Asha Sarma Shekinah D. Malone Josephine M. Ndolo Keejin Yoon Richard D. Dortch Baxter P. Rogers Baxter P. Rogers Baxter P. Rogers Baxter P. Rogers Seth A. Smith Seth A. Smith Seth A. Smith |
| author_facet | Kristin P. O'Grady Kristin P. O'Grady Sanjana Satish Quinn R. Owen Bailey A. Box Francesca Bagnato Francesca Bagnato Anna J. E. Combes Anna J. E. Combes Sarah R. Cook Holly James Westervelt Haley R. Feiler Richard D. Lawless Asha Sarma Shekinah D. Malone Josephine M. Ndolo Keejin Yoon Richard D. Dortch Baxter P. Rogers Baxter P. Rogers Baxter P. Rogers Baxter P. Rogers Seth A. Smith Seth A. Smith Seth A. Smith |
| author_sort | Kristin P. O'Grady |
| collection | DOAJ |
| description | Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can probe tissue biochemistry in vivo with high resolution and sensitivity without requiring exogenous contrast agents. Applying CEST MRI at ultrahigh field provides advantages of increasing spectral resolution and improving sensitivity to metabolites with faster proton exchange rates such as glutamate, a critical neurotransmitter in the brain. Prior magnetic resonance spectroscopy and CEST MRI studies have revealed altered regulation of glutamate in patients with multiple sclerosis (MS). While CEST imaging facilitates new strategies for investigating the pathology underlying this complex and heterogeneous neurological disease, CEST signals are contaminated or diluted by concurrent effects (e.g., semi-solid magnetization transfer (MT) and direct water saturation) and are scaled by the T1 relaxation time of the free water pool which may also be altered in the context of disease. In this study of 20 relapsing-remitting MS patients and age- and sex-matched healthy volunteers, glutamate-weighted CEST data were acquired at 7.0 T. A Lorentzian fitting procedure was used to remove the asymmetric MT contribution from CEST z-spectra, and the apparent exchange-dependent relaxation (AREX) correction was applied using an R1 map derived from an inversion recovery sequence to further isolate glutamate-weighted CEST signals from concurrent effects. Associations between AREX and cognitive function were examined using the Minimal Assessment of Cognitive Function in MS battery. After isolating CEST effects from MT, direct water saturation, and T1 effects, glutamate-weighted AREX contrast remained higher in gray matter than in white matter, though the difference between these tissues decreased. Glutamate-weighted AREX in normal-appearing gray and white matter in MS patients did not differ from healthy gray and white matter but was significantly elevated in white matter lesions. AREX in some cortical regions and in white matter lesions correlated with disability and measures of cognitive function in MS patients. However, further studies with larger sample sizes are needed to confirm these relationships due to potential confounding effects. The application of MT and AREX corrections in this study demonstrates the importance of isolating CEST signals for more specific characterization of the contribution of metabolic changes to tissue pathology and symptoms in MS. |
| first_indexed | 2024-12-20T22:43:24Z |
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| language | English |
| last_indexed | 2024-12-20T22:43:24Z |
| publishDate | 2022-02-01 |
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| series | Frontiers in Neurology |
| spelling | doaj.art-7e6f0c9bcddd4db7b2d3c663d7ca50ae2022-12-21T19:24:26ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-02-011310.3389/fneur.2022.764690764690Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple SclerosisKristin P. O'Grady0Kristin P. O'Grady1Sanjana Satish2Quinn R. Owen3Bailey A. Box4Francesca Bagnato5Francesca Bagnato6Anna J. E. Combes7Anna J. E. Combes8Sarah R. Cook9Holly James Westervelt10Haley R. Feiler11Richard D. Lawless12Asha Sarma13Shekinah D. Malone14Josephine M. Ndolo15Keejin Yoon16Richard D. Dortch17Baxter P. Rogers18Baxter P. Rogers19Baxter P. Rogers20Baxter P. Rogers21Seth A. Smith22Seth A. Smith23Seth A. Smith24Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United StatesVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United StatesVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United StatesVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United StatesNeuroimaging Unit, Division of Neuroimmunology, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Neurology, Nashville VA Medical Center, TN Valley Healthcare System, Nashville, TN, United StatesVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United StatesVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United StatesDivision of Behavioral and Cognitive Neurology, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United StatesVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United StatesVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United StatesSchool of Medicine, Meharry Medical College, Nashville, TN, United StatesDepartment of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United StatesNeuroimaging Unit, Division of Neuroimmunology, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ, United StatesVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, United StatesBiomedical Engineering, Vanderbilt University, Nashville, TN, United StatesVanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United StatesDepartment of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United StatesBiomedical Engineering, Vanderbilt University, Nashville, TN, United StatesChemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can probe tissue biochemistry in vivo with high resolution and sensitivity without requiring exogenous contrast agents. Applying CEST MRI at ultrahigh field provides advantages of increasing spectral resolution and improving sensitivity to metabolites with faster proton exchange rates such as glutamate, a critical neurotransmitter in the brain. Prior magnetic resonance spectroscopy and CEST MRI studies have revealed altered regulation of glutamate in patients with multiple sclerosis (MS). While CEST imaging facilitates new strategies for investigating the pathology underlying this complex and heterogeneous neurological disease, CEST signals are contaminated or diluted by concurrent effects (e.g., semi-solid magnetization transfer (MT) and direct water saturation) and are scaled by the T1 relaxation time of the free water pool which may also be altered in the context of disease. In this study of 20 relapsing-remitting MS patients and age- and sex-matched healthy volunteers, glutamate-weighted CEST data were acquired at 7.0 T. A Lorentzian fitting procedure was used to remove the asymmetric MT contribution from CEST z-spectra, and the apparent exchange-dependent relaxation (AREX) correction was applied using an R1 map derived from an inversion recovery sequence to further isolate glutamate-weighted CEST signals from concurrent effects. Associations between AREX and cognitive function were examined using the Minimal Assessment of Cognitive Function in MS battery. After isolating CEST effects from MT, direct water saturation, and T1 effects, glutamate-weighted AREX contrast remained higher in gray matter than in white matter, though the difference between these tissues decreased. Glutamate-weighted AREX in normal-appearing gray and white matter in MS patients did not differ from healthy gray and white matter but was significantly elevated in white matter lesions. AREX in some cortical regions and in white matter lesions correlated with disability and measures of cognitive function in MS patients. However, further studies with larger sample sizes are needed to confirm these relationships due to potential confounding effects. The application of MT and AREX corrections in this study demonstrates the importance of isolating CEST signals for more specific characterization of the contribution of metabolic changes to tissue pathology and symptoms in MS.https://www.frontiersin.org/articles/10.3389/fneur.2022.764690/fullchemical exchange saturation transfer (CEST)glutamatemultiple sclerosismetabolic imagingultrahigh fieldapparent exchange-dependent relaxation (AREX) |
| spellingShingle | Kristin P. O'Grady Kristin P. O'Grady Sanjana Satish Quinn R. Owen Bailey A. Box Francesca Bagnato Francesca Bagnato Anna J. E. Combes Anna J. E. Combes Sarah R. Cook Holly James Westervelt Haley R. Feiler Richard D. Lawless Asha Sarma Shekinah D. Malone Josephine M. Ndolo Keejin Yoon Richard D. Dortch Baxter P. Rogers Baxter P. Rogers Baxter P. Rogers Baxter P. Rogers Seth A. Smith Seth A. Smith Seth A. Smith Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis Frontiers in Neurology chemical exchange saturation transfer (CEST) glutamate multiple sclerosis metabolic imaging ultrahigh field apparent exchange-dependent relaxation (AREX) |
| title | Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis |
| title_full | Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis |
| title_fullStr | Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis |
| title_full_unstemmed | Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis |
| title_short | Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis |
| title_sort | relaxation compensated chemical exchange saturation transfer mri in the brain at 7t application in relapsing remitting multiple sclerosis |
| topic | chemical exchange saturation transfer (CEST) glutamate multiple sclerosis metabolic imaging ultrahigh field apparent exchange-dependent relaxation (AREX) |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2022.764690/full |
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