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
Hlavní autoři: Nyúl-Tóth, Ádám, Negri, Sharon, Sanford, Madison, Jiang, Raymond, Patai, Roland, Budda, Madeline, Petersen, Benjamin, Pinckard, Jessica, Chandragiri, Siva Sai, Shi, Helen, Reyff, Zeke, Ballard, Cade, Gulej, Rafal, Csik, Boglarka, Ferrier, Jeremy, Balasubramanian, Priya, Yabluchanskiy, Andriy, Cleuren, Audrey, Conley, Shannon, Ungvari, Zoltan, Csiszar, Anna, Tarantini, Stefano
Médium: Journal Article
Jazyk:angličtina
Vydáno: 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.
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
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  organization: Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
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  givenname: Siva Sai
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  organization: Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
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  organization: Iconeus, Paris, France
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  givenname: Audrey
  surname: Cleuren
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  organization: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
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  givenname: Shannon
  orcidid: 0000-0002-7550-3898
  surname: Conley
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  organization: Department of Cellular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
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  givenname: Zoltan
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  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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vascular density
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PublicationTitle Journal of cerebral blood flow and metabolism
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Snippet Intra-vital visualization of deep cerebrovascular structures and blood flow in the aging brain has been a difficult challenge in the field of neurovascular...
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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)
URI https://www.ncbi.nlm.nih.gov/pubmed/38867576
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