Novel intravital approaches to quantify deep vascular structure and perfusion in the aging mouse brain using ultrasound localization microscopy (ULM)
Intra-vital visualization of deep cerebrovascular structures and blood flow in the aging brain has been a difficult challenge in the field of neurovascular research, especially when considering the key role played by the cerebrovasculature in the pathogenesis of both vascular cognitive impairment an...
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| Vydáno v: | Journal of cerebral blood flow and metabolism Ročník 44; číslo 11; s. 1378 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
01.11.2024
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| ISSN: | 1559-7016, 1559-7016 |
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| Abstract | Intra-vital visualization of deep cerebrovascular structures and blood flow in the aging brain has been a difficult challenge in the field of neurovascular research, especially when considering the key role played by the cerebrovasculature in the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Traditional imaging methods face difficulties with the thicker skull of older brains, making high-resolution imaging and cerebral blood flow (CBF) assessment challenging. However, functional ultrasound (fUS) imaging, an emerging non-invasive technique, provides real-time CBF insights with notable spatial-temporal resolution. This study introduces an enhanced longitudinal fUS method for aging brains. Using elderly (24-month C57BL/6) mice, we detail replacing the skull with a polymethylpentene window for consistent fUS imaging over extended periods. Ultrasound localization mapping (ULM), involving the injection of a microbubble (<<10 μm) suspension allows for recording of high-resolution microvascular vessels and flows. ULM relies on the localization and tracking of single circulating microbubbles in the blood flow. A FIJI-based analysis interprets these high-quality ULM visuals. Testing on older mouse brains, our method successfully unveils intricate vascular specifics even in-depth, showcasing its utility for longitudinal studies that require ongoing evaluations of CBF and vascular aspects in aging-focused research. |
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| AbstractList | Intra-vital visualization of deep cerebrovascular structures and blood flow in the aging brain has been a difficult challenge in the field of neurovascular research, especially when considering the key role played by the cerebrovasculature in the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Traditional imaging methods face difficulties with the thicker skull of older brains, making high-resolution imaging and cerebral blood flow (CBF) assessment challenging. However, functional ultrasound (fUS) imaging, an emerging non-invasive technique, provides real-time CBF insights with notable spatial-temporal resolution. This study introduces an enhanced longitudinal fUS method for aging brains. Using elderly (24-month C57BL/6) mice, we detail replacing the skull with a polymethylpentene window for consistent fUS imaging over extended periods. Ultrasound localization mapping (ULM), involving the injection of a microbubble (<<10 μm) suspension allows for recording of high-resolution microvascular vessels and flows. ULM relies on the localization and tracking of single circulating microbubbles in the blood flow. A FIJI-based analysis interprets these high-quality ULM visuals. Testing on older mouse brains, our method successfully unveils intricate vascular specifics even in-depth, showcasing its utility for longitudinal studies that require ongoing evaluations of CBF and vascular aspects in aging-focused research. Intra-vital visualization of deep cerebrovascular structures and blood flow in the aging brain has been a difficult challenge in the field of neurovascular research, especially when considering the key role played by the cerebrovasculature in the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Traditional imaging methods face difficulties with the thicker skull of older brains, making high-resolution imaging and cerebral blood flow (CBF) assessment challenging. However, functional ultrasound (fUS) imaging, an emerging non-invasive technique, provides real-time CBF insights with notable spatial-temporal resolution. This study introduces an enhanced longitudinal fUS method for aging brains. Using elderly (24-month C57BL/6) mice, we detail replacing the skull with a polymethylpentene window for consistent fUS imaging over extended periods. Ultrasound localization mapping (ULM), involving the injection of a microbubble (<<10 μm) suspension allows for recording of high-resolution microvascular vessels and flows. ULM relies on the localization and tracking of single circulating microbubbles in the blood flow. A FIJI-based analysis interprets these high-quality ULM visuals. Testing on older mouse brains, our method successfully unveils intricate vascular specifics even in-depth, showcasing its utility for longitudinal studies that require ongoing evaluations of CBF and vascular aspects in aging-focused research.Intra-vital visualization of deep cerebrovascular structures and blood flow in the aging brain has been a difficult challenge in the field of neurovascular research, especially when considering the key role played by the cerebrovasculature in the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Traditional imaging methods face difficulties with the thicker skull of older brains, making high-resolution imaging and cerebral blood flow (CBF) assessment challenging. However, functional ultrasound (fUS) imaging, an emerging non-invasive technique, provides real-time CBF insights with notable spatial-temporal resolution. This study introduces an enhanced longitudinal fUS method for aging brains. Using elderly (24-month C57BL/6) mice, we detail replacing the skull with a polymethylpentene window for consistent fUS imaging over extended periods. Ultrasound localization mapping (ULM), involving the injection of a microbubble (<<10 μm) suspension allows for recording of high-resolution microvascular vessels and flows. ULM relies on the localization and tracking of single circulating microbubbles in the blood flow. A FIJI-based analysis interprets these high-quality ULM visuals. Testing on older mouse brains, our method successfully unveils intricate vascular specifics even in-depth, showcasing its utility for longitudinal studies that require ongoing evaluations of CBF and vascular aspects in aging-focused research. |
| Author | Ungvari, Zoltan Pinckard, Jessica Gulej, Rafal Csiszar, Anna Ballard, Cade Conley, Shannon Negri, Sharon Chandragiri, Siva Sai Cleuren, Audrey Csik, Boglarka Yabluchanskiy, Andriy Sanford, Madison Tarantini, Stefano Jiang, Raymond Reyff, Zeke Patai, Roland Balasubramanian, Priya Shi, Helen Petersen, Benjamin Nyúl-Tóth, Ádám Budda, Madeline Ferrier, Jeremy |
| Author_xml | – sequence: 1 givenname: Ádám surname: Nyúl-Tóth fullname: Nyúl-Tóth, Ádám organization: International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary – sequence: 2 givenname: Sharon surname: Negri fullname: Negri, Sharon organization: Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA – sequence: 3 givenname: Madison surname: Sanford fullname: Sanford, Madison organization: Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA – sequence: 4 givenname: Raymond surname: Jiang fullname: Jiang, Raymond organization: Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA – sequence: 5 givenname: Roland surname: Patai fullname: Patai, Roland organization: Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA – sequence: 6 givenname: Madeline orcidid: 0000-0001-7825-9555 surname: Budda fullname: Budda, Madeline organization: Department of Cellular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA – sequence: 7 givenname: Benjamin surname: Petersen fullname: Petersen, Benjamin organization: Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA – sequence: 8 givenname: Jessica surname: Pinckard fullname: Pinckard, Jessica organization: Department of Cellular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA – sequence: 9 givenname: Siva Sai surname: Chandragiri fullname: Chandragiri, Siva Sai organization: Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA – sequence: 10 givenname: Helen orcidid: 0009-0005-6893-0188 surname: Shi fullname: Shi, Helen organization: Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA – sequence: 11 givenname: Zeke surname: Reyff fullname: Reyff, Zeke organization: Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA – sequence: 12 givenname: Cade surname: Ballard fullname: Ballard, Cade organization: Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA – sequence: 13 givenname: Rafal orcidid: 0000-0002-9958-707X surname: Gulej fullname: Gulej, Rafal organization: Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA – sequence: 14 givenname: Boglarka surname: Csik fullname: Csik, Boglarka organization: Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA – sequence: 15 givenname: Jeremy surname: Ferrier fullname: Ferrier, Jeremy organization: Iconeus, Paris, France – sequence: 16 givenname: Priya surname: Balasubramanian fullname: Balasubramanian, Priya organization: Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA – sequence: 17 givenname: Andriy surname: Yabluchanskiy fullname: Yabluchanskiy, Andriy organization: Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA – sequence: 18 givenname: Audrey surname: Cleuren fullname: Cleuren, Audrey organization: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA – sequence: 19 givenname: Shannon orcidid: 0000-0002-7550-3898 surname: Conley fullname: Conley, Shannon organization: Department of Cellular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA – sequence: 20 givenname: Zoltan surname: Ungvari fullname: Ungvari, Zoltan organization: Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA – sequence: 21 givenname: Anna surname: Csiszar fullname: Csiszar, Anna organization: International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary – sequence: 22 givenname: Stefano surname: Tarantini fullname: Tarantini, Stefano organization: Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA |
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| SubjectTerms | Aging - physiology Animals Brain - blood supply Brain - diagnostic imaging Cerebrovascular Circulation - physiology Intravital Microscopy - methods Male Mice Mice, Inbred C57BL Microbubbles Ultrasonography - methods |
| Title | Novel intravital approaches to quantify deep vascular structure and perfusion in the aging mouse brain using ultrasound localization microscopy (ULM) |
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