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1.
Sci Rep ; 14(1): 15338, 2024 07 03.
Article in English | MEDLINE | ID: mdl-38961135

ABSTRACT

Blood-brain barrier (BBB) disruption may contribute to cognitive decline, but questions remain whether this association is more pronounced for certain brain regions, such as the hippocampus, or represents a whole-brain mechanism. Further, whether human BBB leakage is triggered by excessive vascular pulsatility, as suggested by animal studies, remains unknown. In a prospective cohort (N = 50; 68-84 years), we used contrast-enhanced MRI to estimate the permeability-surface area product (PS) and fractional plasma volume ( v p ), and 4D flow MRI to assess cerebral arterial pulsatility. Cognition was assessed by the Montreal Cognitive Assessment (MoCA) score. We hypothesized that high PS would be associated with high arterial pulsatility, and that links to cognition would be specific to hippocampal PS. For 15 brain regions, PS ranged from 0.38 to 0.85 (·10-3 min-1) and v p from 0.79 to 1.78%. Cognition was related to PS (·10-3 min-1) in hippocampus (ß = - 2.9; p = 0.006), basal ganglia (ß = - 2.3; p = 0.04), white matter (ß = - 2.6; p = 0.04), whole-brain (ß = - 2.7; p = 0.04) and borderline-related for cortex (ß = - 2.7; p = 0.076). Pulsatility was unrelated to PS for all regions (p > 0.19). Our findings suggest PS-cognition links mainly reflect a whole-brain phenomenon with only slightly more pronounced links for the hippocampus, and provide no evidence of excessive pulsatility as a trigger of BBB disruption.


Subject(s)
Blood-Brain Barrier , Cognition , Magnetic Resonance Imaging , Humans , Blood-Brain Barrier/diagnostic imaging , Aged , Male , Female , Cognition/physiology , Aged, 80 and over , Pulsatile Flow , Cerebral Arteries/diagnostic imaging , Cerebral Arteries/physiology , Prospective Studies , Hippocampus/diagnostic imaging , Hippocampus/physiology , Brain/diagnostic imaging , Brain/physiology , Brain/blood supply , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/diagnostic imaging
2.
NMR Biomed ; 37(7): e5082, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38124351

ABSTRACT

Neurological disorders can manifest with altered neurofluid dynamics in different compartments of the central nervous system. These include alterations in cerebral blood flow, cerebrospinal fluid (CSF) flow, and tissue biomechanics. Noninvasive quantitative assessment of neurofluid flow and tissue motion is feasible with phase contrast magnetic resonance imaging (PC MRI). While two-dimensional (2D) PC MRI is routinely utilized in research and clinical settings to assess flow dynamics through a single imaging slice, comprehensive neurofluid dynamic assessment can be limited or impractical. Recently, four-dimensional (4D) flow MRI (or time-resolved three-dimensional PC with three-directional velocity encoding) has emerged as a powerful extension of 2D PC, allowing for large volumetric coverage of fluid velocities at high spatiotemporal resolution within clinically reasonable scan times. Yet, most 4D flow studies have focused on blood flow imaging. Characterizing CSF flow dynamics with 4D flow (i.e., 4D CSF flow) is of high interest to understand normal brain and spine physiology, but also to study neurological disorders such as dysfunctional brain metabolite waste clearance, where CSF dynamics appear to play an important role. However, 4D CSF flow imaging is challenged by the long T1 time of CSF and slower velocities compared with blood flow, which can result in longer scan times from low flip angles and extended motion-sensitive gradients, hindering clinical adoption. In this work, we review the state of 4D CSF flow MRI including challenges, novel solutions from current research and ongoing needs, examples of clinical and research applications, and discuss an outlook on the future of 4D CSF flow.


Subject(s)
Cerebrospinal Fluid , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Humans , Cerebrospinal Fluid/diagnostic imaging , Cerebrospinal Fluid/physiology , Animals , Hydrodynamics , Cerebrovascular Circulation/physiology , Rheology
3.
Sci Rep ; 12(1): 20957, 2022 12 05.
Article in English | MEDLINE | ID: mdl-36470934

ABSTRACT

Cognitive functions are well-preserved for some older individuals, but the underlying brain mechanisms remain disputed. Here, 5-year longitudinal 3-back in-scanner and offline data classified individuals in a healthy older sample (baseline age = 64-68 years) into having stable or declining working-memory (WM). Consistent with a vital role of the prefrontal cortex (PFC), WM stability or decline was related to maintained or reduced longitudinal PFC functional responses. Subsequent analyses of imaging markers of general brain maintenance revealed higher levels in the stable WM group on measures of neurotransmission and vascular health. Also, categorical and continuous analyses showed that rate of WM decline was related to global (ventricles) and local (hippocampus) measures of neuronal integrity. Thus, our findings support a role of the PFC as well as general brain maintenance in explaining heterogeneity in longitudinal WM trajectories in aging.


Subject(s)
Brain , Memory, Short-Term , Humans , Middle Aged , Aged , Memory, Short-Term/physiology , Brain/diagnostic imaging , Brain/physiology , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiology , Brain Mapping , Aging/physiology , Magnetic Resonance Imaging
4.
Ann Neurol ; 92(5): 871-881, 2022 11.
Article in English | MEDLINE | ID: mdl-36054261

ABSTRACT

OBJECTIVE: High cerebral arterial pulsatility index (PI), white matter lesions (WMLs), enlarged perivascular spaces (PVSs), and lacunar infarcts are common findings in the elderly population, and considered indicators of small vessel disease (SVD). Here, we investigate the potential temporal ordering among these variables, with emphasis on determining whether high PI is an early or delayed manifestation of SVD. METHODS: In a population-based cohort, 4D flow MRI data for cerebral arterial pulsatility was collected for 159 participants at baseline (age 64-68), and for 122 participants at follow-up 5 years later. Structural MRI was used for WML and PVS segmentation, and lacune identification. Linear mixed-effects (LME) models were used to model longitudinal changes testing for pairwise associations, and latent change score (LCS) models to model multiple relationships among variables simultaneously. RESULTS: Longitudinal 5-year increases were found for WML, PVS, and PI. Cerebral arterial PI at baseline did not predict changes in WML or PVS volume. However, WML and PVS volume at baseline predicted 5-year increases in PI. This was shown for PI increases in relation to baseline WML and PVS volumes using LME models (R  ≥  0.24; p < 0.02 and R  ≥  0.23; p < 0.03, respectively) and LCS models ( ß  = 0.28; p = 0.015 and ß  = 0.28; p = 0.009, respectively). Lacunes at baseline were unrelated to PI. INTERPRETATION: In healthy older adults, indicators of SVD are related in a lead-lag fashion, in which the expression of WML and PVS precedes increases in cerebral arterial PI. Hence, we propose that elevated PI is a relatively late manifestation, rather than a risk factor, for cerebral SVD. ANN NEUROL 2022;92:871-881.


Subject(s)
Cerebral Small Vessel Diseases , Glymphatic System , Nervous System Diseases , Stroke, Lacunar , White Matter , Humans , Aged , Middle Aged , White Matter/diagnostic imaging , White Matter/pathology , Dilatation , Cerebral Small Vessel Diseases/epidemiology , Glymphatic System/diagnostic imaging , Stroke, Lacunar/pathology , Nervous System Diseases/pathology
5.
J Cereb Blood Flow Metab ; 41(7): 1778-1790, 2021 07.
Article in English | MEDLINE | ID: mdl-33444091

ABSTRACT

Microvascular damage in the hippocampus is emerging as a central cause of cognitive decline and dementia in aging. This could be a consequence of age-related decreases in vascular elasticity, exposing hippocampal capillaries to excessive cardiac-related pulsatile flow that disrupts the blood-brain barrier and the neurovascular unit. Previous studies have found altered intracranial hemodynamics in cognitive impairment and dementia, as well as negative associations between pulsatility and hippocampal volume. However, evidence linking features of the cerebral arterial flow waveform to hippocampal function is lacking. We used a high-resolution 4D flow MRI approach to estimate global representations of the time-resolved flow waveform in distal cortical arteries and in proximal arteries feeding the brain in healthy older adults. Waveform-based clustering revealed a group of individuals featuring steep systolic onset and high amplitude that had poorer hippocampus-sensitive episodic memory (p = 0.003), lower whole-brain perfusion (p = 0.001), and weaker microvascular low-frequency oscillations in the hippocampus (p = 0.035) and parahippocampal gyrus (p = 0.005), potentially indicating compromised neurovascular unit integrity. Our findings suggest that aberrant hemodynamic forces contribute to cerebral microvascular and hippocampal dysfunction in aging.


Subject(s)
Aging , Brain/blood supply , Cerebral Arteries/physiology , Cognitive Dysfunction/physiopathology , Hippocampus/physiology , Memory, Episodic , Pulsatile Flow , Aged , Cerebrovascular Circulation , Female , Healthy Volunteers , Hippocampus/blood supply , Humans , Male , Middle Aged , Vascular Stiffness
6.
J Cereb Blood Flow Metab ; 40(12): 2429-2440, 2020 12.
Article in English | MEDLINE | ID: mdl-31722598

ABSTRACT

Recent reports have suggested that age-related arterial stiffening and excessive cerebral arterial pulsatility cause blood-brain barrier breakdown, brain atrophy and cognitive decline. This has spurred interest in developing non-invasive methods to measure pulsatility in distal vessels, closer to the cerebral microcirculation. Here, we report a method based on four-dimensional (4D) flow MRI to estimate a global composite flow waveform of distal cerebral arteries. The method is based on finding and sampling arterial waveforms from thousands of cross sections in numerous small vessels of the brain, originating from cerebral cortical arteries. We demonstrate agreement with internal and external reference methods and show the ability to capture significant increases in distal cerebral arterial pulsatility as a function of age. The proposed approach can be used to advance our understanding regarding excessive arterial pulsatility as a potential trigger of cognitive decline and dementia.


Subject(s)
Brain/blood supply , Cerebral Arteries/diagnostic imaging , Magnetic Resonance Imaging/methods , Pulsatile Flow/physiology , Aged , Aged, 80 and over , Aging/physiology , Atrophy/diagnostic imaging , Blood-Brain Barrier/pathology , Brain/pathology , Cerebral Arteries/physiopathology , Cognitive Dysfunction/physiopathology , Female , Hemodynamics/physiology , Humans , Male , Microcirculation/physiology , Middle Aged
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