Diffusion Tensor Imaging and Chemical Exchange Saturation Transfer MRI Evaluation on the Long-Term Effects of Pulsed Focused Ultrasound and Microbubbles Blood Brain Barrier Opening in the Rat
Blood-brain barrier opening (BBBO) with pulsed Focused Ultrasound (pFUS) and microbubbles (MB) has received increasing interest as a method for neurotherapeutics of the central nervous system. In general, conventional MRI [i.e., T2w, T2∗w, gadolinium (Gd) enhanced T1w] is used to monitor the effects...
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doaj-eda5a8c1a5d74818b1d84eb72c05f3b52020-11-25T03:39:30ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-08-011410.3389/fnins.2020.00908567897Diffusion Tensor Imaging and Chemical Exchange Saturation Transfer MRI Evaluation on the Long-Term Effects of Pulsed Focused Ultrasound and Microbubbles Blood Brain Barrier Opening in the RatTsang-Wei Tu0Tsang-Wei Tu1Tsang-Wei Tu2Zsofia I. Kovacs3Zsofia I. Kovacs4Maggie Sundby5Jaclyn A. Witko6Jaclyn A. Witko7Georgios Z. Papadakis8William C. Reid9Dima A. Hammoud10Joseph A. Frank11Joseph A. Frank12Molecular Imaging Laboratory, Department of Radiology, Howard University College of Medicine, Washington, DC, United StatesFrank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United StatesCenter for Neuroscience and Regenerative Medicine, Henry Jackson Foundation, Bethesda, MD, United StatesFrank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United StatesInstitute for Biomedical Engineering, Swiss Federal Institute of Technology, Zurich, SwitzerlandFrank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United StatesFrank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United StatesCenter for Neuroscience and Regenerative Medicine, Henry Jackson Foundation, Bethesda, MD, United StatesCenter for Infectious Disease Imaging, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United StatesCenter for Infectious Disease Imaging, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United StatesCenter for Infectious Disease Imaging, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United StatesFrank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United StatesNational Institute of Biomedical Imaging and Bioengineering, National Institutes of Health (NIH), Bethesda, MD, United StatesBlood-brain barrier opening (BBBO) with pulsed Focused Ultrasound (pFUS) and microbubbles (MB) has received increasing interest as a method for neurotherapeutics of the central nervous system. In general, conventional MRI [i.e., T2w, T2∗w, gadolinium (Gd) enhanced T1w] is used to monitor the effects of pFUS+MB on BBBO and/or assess whether sonication results in parenchymal damage. This study employed multimodal MRI techniques and 18F-Fludeoxyglucose (FDG) PET to evaluate the effects of single and multiple weekly pFUS+MB sessions on morphology and glucose utilization levels in the rat cortex and hippocampus. pFUS was performed with 0.548 MHz transducer with a slow infusion over 1 min of OptisonTM (5–8 × 107 MB) in nine focal points in cortex and four in hippocampus. During pFUS+MB treatment, Gd-T1w was performed at 3 T to confirm BBBO, along with subsequent T2w, T2∗w, DTI and glucose CEST (glucoCEST)-weighted imaging by high field 9.4 T and compared with FDG-PET and immunohistochemistry. Animals receiving a single pFUS+MB exhibited minimal hypointense voxels on T2∗w. Brains receiving multiple pFUS+MB treatments demonstrated persistent T2w and T2∗ abnormalities associated with changes in DTI and glucoCEST when compared to contralateral parenchyma. Decreased glucoCEST contrast was substantiated by FDG-PET in cortex following multiple sonications. Immunohistochemistry showed significantly dilated vessels and decreased neuronal glucose transporter (GLUT3) expression in sonicated cortex and hippocampus without changes in neuronal counts. These results suggest the importance to standardize MRI protocols in concert with advanced imaging techniques when evaluating long term effects of pFUS+MB BBBO in clinical trials for neurological diseases.https://www.frontiersin.org/article/10.3389/fnins.2020.00908/fullpFUS microbubbleblood brain barrierT2∗ abnormalityDTICESTFDG-PET |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tsang-Wei Tu Tsang-Wei Tu Tsang-Wei Tu Zsofia I. Kovacs Zsofia I. Kovacs Maggie Sundby Jaclyn A. Witko Jaclyn A. Witko Georgios Z. Papadakis William C. Reid Dima A. Hammoud Joseph A. Frank Joseph A. Frank |
spellingShingle |
Tsang-Wei Tu Tsang-Wei Tu Tsang-Wei Tu Zsofia I. Kovacs Zsofia I. Kovacs Maggie Sundby Jaclyn A. Witko Jaclyn A. Witko Georgios Z. Papadakis William C. Reid Dima A. Hammoud Joseph A. Frank Joseph A. Frank Diffusion Tensor Imaging and Chemical Exchange Saturation Transfer MRI Evaluation on the Long-Term Effects of Pulsed Focused Ultrasound and Microbubbles Blood Brain Barrier Opening in the Rat Frontiers in Neuroscience pFUS microbubble blood brain barrier T2∗ abnormality DTI CEST FDG-PET |
author_facet |
Tsang-Wei Tu Tsang-Wei Tu Tsang-Wei Tu Zsofia I. Kovacs Zsofia I. Kovacs Maggie Sundby Jaclyn A. Witko Jaclyn A. Witko Georgios Z. Papadakis William C. Reid Dima A. Hammoud Joseph A. Frank Joseph A. Frank |
author_sort |
Tsang-Wei Tu |
title |
Diffusion Tensor Imaging and Chemical Exchange Saturation Transfer MRI Evaluation on the Long-Term Effects of Pulsed Focused Ultrasound and Microbubbles Blood Brain Barrier Opening in the Rat |
title_short |
Diffusion Tensor Imaging and Chemical Exchange Saturation Transfer MRI Evaluation on the Long-Term Effects of Pulsed Focused Ultrasound and Microbubbles Blood Brain Barrier Opening in the Rat |
title_full |
Diffusion Tensor Imaging and Chemical Exchange Saturation Transfer MRI Evaluation on the Long-Term Effects of Pulsed Focused Ultrasound and Microbubbles Blood Brain Barrier Opening in the Rat |
title_fullStr |
Diffusion Tensor Imaging and Chemical Exchange Saturation Transfer MRI Evaluation on the Long-Term Effects of Pulsed Focused Ultrasound and Microbubbles Blood Brain Barrier Opening in the Rat |
title_full_unstemmed |
Diffusion Tensor Imaging and Chemical Exchange Saturation Transfer MRI Evaluation on the Long-Term Effects of Pulsed Focused Ultrasound and Microbubbles Blood Brain Barrier Opening in the Rat |
title_sort |
diffusion tensor imaging and chemical exchange saturation transfer mri evaluation on the long-term effects of pulsed focused ultrasound and microbubbles blood brain barrier opening in the rat |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2020-08-01 |
description |
Blood-brain barrier opening (BBBO) with pulsed Focused Ultrasound (pFUS) and microbubbles (MB) has received increasing interest as a method for neurotherapeutics of the central nervous system. In general, conventional MRI [i.e., T2w, T2∗w, gadolinium (Gd) enhanced T1w] is used to monitor the effects of pFUS+MB on BBBO and/or assess whether sonication results in parenchymal damage. This study employed multimodal MRI techniques and 18F-Fludeoxyglucose (FDG) PET to evaluate the effects of single and multiple weekly pFUS+MB sessions on morphology and glucose utilization levels in the rat cortex and hippocampus. pFUS was performed with 0.548 MHz transducer with a slow infusion over 1 min of OptisonTM (5–8 × 107 MB) in nine focal points in cortex and four in hippocampus. During pFUS+MB treatment, Gd-T1w was performed at 3 T to confirm BBBO, along with subsequent T2w, T2∗w, DTI and glucose CEST (glucoCEST)-weighted imaging by high field 9.4 T and compared with FDG-PET and immunohistochemistry. Animals receiving a single pFUS+MB exhibited minimal hypointense voxels on T2∗w. Brains receiving multiple pFUS+MB treatments demonstrated persistent T2w and T2∗ abnormalities associated with changes in DTI and glucoCEST when compared to contralateral parenchyma. Decreased glucoCEST contrast was substantiated by FDG-PET in cortex following multiple sonications. Immunohistochemistry showed significantly dilated vessels and decreased neuronal glucose transporter (GLUT3) expression in sonicated cortex and hippocampus without changes in neuronal counts. These results suggest the importance to standardize MRI protocols in concert with advanced imaging techniques when evaluating long term effects of pFUS+MB BBBO in clinical trials for neurological diseases. |
topic |
pFUS microbubble blood brain barrier T2∗ abnormality DTI CEST FDG-PET |
url |
https://www.frontiersin.org/article/10.3389/fnins.2020.00908/full |
work_keys_str_mv |
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