White matter perfusion declines in aging are related to developmental trajectory, not fibre calibre
Poster No:
2609
Submission Type:
Abstract Submission
Authors:
Tyler Robinson1, Yutong Sun1, Jordan Chad1, Paul Chang2, J. Jean Chen3
Institutions:
1Rotman Research Institute, Baycrest, Toronto, Ontario, 2Rotman Reserach Institute, Baycrest, Toronto, Ontario, 3Baycrest Health Sciences, Toronto, Ontario
First Author:
Co-Author(s):
Introduction:
Our work recently uncovered tract-specific white-matter (WM) perfusion declines in aging, which may predate microstructural declines(7). This study investigates the relationships between perfusion declines and WM development as well as physiology. Regions that develop first are often expected to deteriorate the last, i.e. "last-in-first-out"(5,8). Alternatively, regions which develop most rapidly may also decline most rapidly in aging, or the "gains-predict-loss" model(8). The validity of such theories remains uncertain, in part due to lack of clarity on the definition of developmental order(3,6,8). Furthermore, it is informative to link perfusion to fibre metabolic need, which varies with fibre size(9). This study uses HCP-A data to elucidate the relationship amongst perfusion decline, fibre calibre and tract developmental order.
Methods:
535 data sets from healthy subjects (300 female, aged 36-100) were drawn from the HCP-A study (OMB Control# 0925-0667)(2), including diffusion-weighted MRI (93 directions at b=1500s/mm2 at 1.5mm isotropic resolution), and a multi-delay pseudo-continuous arterial spin labeling (pCASL) data set at 1.5mm3 voxel resolution. We corrected for eddy-current and susceptibility-related distortions via EDDY. FreeSurfer TRACULA (v 7.2.0)(10) was used to provide 10 bilateral tract segmentations in subject space. Cerebral blood flow (CBF) and arterial transit time (ATT) were assessed using FSL oxford_ASL, and raw CBF and ATT values were normalized to the youngest 50 subjects to produce CBFperc, and ATTperc values. We defined 6 models to help explain perfusion age effects:
Last-in-first-out models;
(1) "Last-appearing-first-out" (LAFO): ordered by time of prenatal emergence(6)
(2) "Last-myelinated-first-out" (LMFO): ordered by time of peak R1 ("myelination") at birth(3)
Gain-predicts-loss models;
(3) "Slowest-peak-first-out" (SPFO-MD): ordered by rate of MD change from adolescence to adult peak(8)
(4) "Slowest-myelinated-first-out (SMFO): ordered by rate of R1 change from adolescence to adult peak(8)
Physiological models:
(5) "Axon-diameter-determined" (ADD): ordered by mean axon diameter at birth(4)
(6) "Vascular-diameter-determined" (VDD): ordered by mean macrovascular density(1)
The predictiveness of these models was assessed using multivariate regression in R (version 4.1.1), with sex as a covariate of no interest.
Last-in-first-out models;
(1) "Last-appearing-first-out" (LAFO): ordered by time of prenatal emergence(6)
(2) "Last-myelinated-first-out" (LMFO): ordered by time of peak R1 ("myelination") at birth(3)
Gain-predicts-loss models;
(3) "Slowest-peak-first-out" (SPFO-MD): ordered by rate of MD change from adolescence to adult peak(8)
(4) "Slowest-myelinated-first-out (SMFO): ordered by rate of R1 change from adolescence to adult peak(8)
Physiological models:
(5) "Axon-diameter-determined" (ADD): ordered by mean axon diameter at birth(4)
(6) "Vascular-diameter-determined" (VDD): ordered by mean macrovascular density(1)
The predictiveness of these models was assessed using multivariate regression in R (version 4.1.1), with sex as a covariate of no interest.
Results:
Age-related declines in CBFperc and lengthening of ATT were identified in the majority of tracts.
Both last-in-first-out models identified linear relationships between mean CBFperc/ATTperc and order of tract development (Fig. 1). In the LAFO model, tract order was negatively associated with both CBFperc and ATTperc. In the LMFO model, CBFperc associated positively with tract order while ATTperc associated negatively.
The LAFO order was negatively associated with rates of age-related differences in both CBFperc and ATTperc. No interaction between tract-order and age-related CBFperc/ATTperc differences was observed in the LMFO model (Fig. 2).
No contribution to CBF or ATT declines by tract order were detected in the gain-predicts-loss models (SPFO-MD, SMFO) or the physiological determinant models (ADD, VDD).
Both last-in-first-out models identified linear relationships between mean CBFperc/ATTperc and order of tract development (Fig. 1). In the LAFO model, tract order was negatively associated with both CBFperc and ATTperc. In the LMFO model, CBFperc associated positively with tract order while ATTperc associated negatively.
The LAFO order was negatively associated with rates of age-related differences in both CBFperc and ATTperc. No interaction between tract-order and age-related CBFperc/ATTperc differences was observed in the LMFO model (Fig. 2).
No contribution to CBF or ATT declines by tract order were detected in the gain-predicts-loss models (SPFO-MD, SMFO) or the physiological determinant models (ADD, VDD).
Conclusions:
Our previous findings identified two main regimes of WM perfusion decline: namely reduced CBF with relatively preserved ATT, and prolonged ATT with relatively preserved CBF(7). Our current findings suggest that later emerging tracts have both lower CBFperc and shorter ATTperc later in life. They also suggest that tracts last to fully myelinate have higher CBFperc and shorter ATTperc later in life. These include WM regions responsible for higher cognitive function, which may be preferentially perfused. However, in such regions, we also found evidence for faster decreases in CBFperc but preserved ATTperc in aging. These findings suggest that myelination order may determine the regime of perfusion decline aging, with distinctive functional consequences.
Lifespan Development:
Aging 2
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity
Physiology, Metabolism and Neurotransmission :
Cerebral Metabolism and Hemodynamics 1
Physiology, Metabolism and Neurotransmission Other
Keywords:
Aging
Cerebral Blood Flow
Development
Tractography
White Matter
1|2Indicates the priority used for review
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