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Mapping the Age Effect on Cortical Arterial Arrival Time and Perfusion using multi-delay pCASL
Yutong Sun1, Paul T.H Chang 1, and J. Jean Chen2
1Rotman Research Institute, Baycrest Health Sciences, Toronto, ON, Canada, 2Medical Biophysics, University of Toronto, Toronto, ON, Canada

Synopsis

Multi-delay arterial spin labeling (ASL) has made it possible to non-invasively quantify cerebral hemodynamic changes in aging, including cerebral blood flow (CBF) and arterial arrival time (ATT). However, limited numbers of studies exist to focus on the spatial heterogeneity of age effects on both CBF and ATT. In this study, we map the relationships between age, CBF and ATT on the cerebral cortex using multi-delay pseudo-continuous ASL (pCASL) data from the Human Connectome Project in Aging.

Introduction

Multi-delay pCASL provides reliable measures on both CBF and ATT. CBF measures the volume of arterial blood delivered to 100g of brain tissue per minute; ATT describes the time it takes for the labeled blood to travel from the tagging plane to the brain tissue3,4. While the effect of healthy aging on CBF has been heavily studied, ATT is less comprehensively studied, although it also provides important physiologic information on the status of hemodynamic alteration5. Prior research has shown that CBF progressively decreases during aging while ATT is positively associated with age in whole-brain or specific regions-of-interest (ROIs)6,7. Recent studies also indicated that the age-hemodynamic association as revealed by CBF and ATT is region-dependent 8,9, but there has yet to be a study showing variations in ATT-age associations (in conjunction with CBF) across the brain. Thus, the present study aims to study age-related hemodynamics by examining and comparing the magnitude of CBF and ATT changes with age across the cerebral cortex.

Methods

Multi-delay pseudo-continuous ASL (pCASL) in the Human Connectome Project-Aging (HCP-A) Lifespan Study helps understand the age-associated hemodynamic changes across the brain1-3. All subjects of this study were participants of the HCP-A Lifespan Study3, which is made of adults without major diagnosed diseases that cause cognitive declines such as stroke and dementia10. Additional manual quality control leads to the exclusion of 147 out of 689 subjects. The final sample consists of 542 subjects aged 36-100, among which, there are 306 females and 236 males.

pCASL images were obtained on a Siemens Prisma 3 Tesla scanner using a 2D MB-EPI strategy3. Five post-labeling delays (0.7, 1.2, 1.7, 2.2, 2.7 s) were applied and a tag and control pair is included in each repeat3, which gave a total of 86 frames with an additional 2 frames for the calibration images.

For data processing, TOPUP was used to correct susceptibility-induced distortions, and then OXFORD-ASL was used to quantify CBF and ATT and also to correct for the partial volume effects11,12. Cortical reconstruction was performed with the structural MRI (MPRAGE) data from the same dataset using the software FreeSurfer13. With the same software, CBF and ATT maps were projected onto the cortical surface and then registered to a standard (fsaverage) space.

Voxelwise linear fitting was conducted and the effect size (difference in metric per year) was computed with FreeSurfer’s mri_glmfit14. Clusterwise correction was done for multiple comparisons with the cluster-defining threshold set p<0.05, and alpha=0.05.

Results

Increasing ATT with age was observed in the cortical grey matter with a mean slope of +0.0002s per year for both left and right hemispheres (Figure 1). CBF is found to be inversely associated with age with the slope of -0.373 ml/100g/min for the left hemisphere and -0.402 ml/100g/min for the right hemisphere (Figure 2).

Figure 3 shows the widespread positive association between ATT and age across the cerebral cortex, with the effect size masked by significant clusters. The highest magnitude of age-associated lengthening of ATT was identified in the supramarginal, postcentral, precentral, caudal middle frontal, lingual and precuneus gyrus on both hemispheres. Figure 4 displays negative associations of CBF with age across the cerebral cortex. The peak age effects are distributed on the lateral occipital, postcentral, rostral middle frontal and superior frontal regions of both the right and left cortex. The peak age effects for CBF and ATT do not overlap.

Discussion and Conclusion

In this study, we examined how hemodynamics could gradually change on the cerebral cortex in a typical aging process. An overall positive association of ATT with age and a negative association of CBF with age was described, which is in good agreement with previous ASL studies6,15-17. More importantly, we found that the changes of CBF and ATT with age are not uniform across cortical regions. The lack of spatial overlap between ATT and CBF age effects highlights the necessity of bringing ATT onto the table to be interpreted jointly with CBF. Note that in this work, CBF is quantified using the ATT estimation, thus conventional single-delay ASL results could confound long ATTs with low CBFs. Furthermore, our CBF and ATT estimates are corrected for partial-volume effects, but the pattern of ATT-age associations rather resembles that of age-related cortical thinning (REF). This potential link will be studied in depth in our future work.

Acknowledgements

This research has been conducted using the HCP-A data. We thank the CIHR and NSERC for funding support.

References

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10. Bookheimer SY, Salat DH, Terpstra M, Ances BM, Barch DM, Buckner RL, Burgess GC, Curtiss SW, Diaz-Santos M, Elam JS, Fischl B. The lifespan human connectome project in aging: an overview. Neuroimage. 2019 Jan 15;185:335-48.

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Figures

Figure 1. Scatter plots of mean arterial arrival time (ATT) versus age on the left cerebral hemisphere cortex (left) and the right cerebral hemisphere cortex (right). Age associations are significantly positive with a linear regression equation to show the extent of estimated change of ATT is +0.002s per year.

Figure 2. Scatter plots of mean cerebral blood flow (CBF) versus age on the left cerebral hemisphere cortex (left) and the right cerebral hemisphere cortex (right). Age associations are significantly negative with a linear regression equation to show the extent of estimated change of CBF is -0.373 ml/100g/min per year on the left cortex and -0.402 ml/100g/min per year on the right cortex.

Figure 3. Surface display of the age-related differences in ATT (s) per year in significant clusters. A widespread positive correlation between age and ATT across the cortex is found with peak differences on the lateral pre- and post-central gyrus, supramarginal, caudal middle frontal, lingual and precuneus gyrus. Associations are not found significant on the paracentral gyrus and part of the inferior temporal lobe.

Figure 4. Surface display of the age-related differences in CBF (ml/100g/min) per year in significant clusters. A widespread negative correlation between age and CBF across the cortex is found with peak differences on the rostral middle and superior frontal gyrus, and lateral occipital gyri. Associations are not found significant on a large portion of the superior temporal lobe, and part of the middle and inferior temporal lobes.

Proc. Intl. Soc. Mag. Reson. Med. 30 (2022)
4877
DOI: https://doi.org/10.58530/2022/4877