Mapping cortical-depth-dependent vascular responses in cerebral amyloid angiopathy with 7T fMRI

Poster No:

1692 

Submission Type:

Abstract Submission 

Authors:

Jennifer Yeo1, Nana Frimpong2, Aina Frau-Pascual2,3, Mitchell Horn2, Isik Karahanoglu2,3, Suk-Tak Chan2,3, Andrew Warren2, Susanne van Veluw2,3, Edip Gurol2,3, Jonathan Polimeni2,3, Steven Greenberg2,3, Jingyuan Chen2,3

Institutions:

1Northeastern University, Boston, MA, 2Massachusetts General Hospital, Boston, MA, 3Harvard Medical School, Boston, MA

First Author:

Jennifer Yeo  
Northeastern University
Boston, MA

Co-Author(s):

Nana Frimpong  
Massachusetts General Hospital
Boston, MA
Aina Frau-Pascual  
Massachusetts General Hospital|Harvard Medical School
Boston, MA|Boston, MA
Mitchell Horn  
Massachusetts General Hospital
Boston, MA
Isik Karahanoglu  
Massachusetts General Hospital|Harvard Medical School
Boston, MA|Boston, MA
Suk-Tak Chan  
Massachusetts General Hospital|Harvard Medical School
Boston, MA|Boston, MA
Andrew Warren  
Massachusetts General Hospital
Boston, MA
Susanne van Veluw  
Massachusetts General Hospital|Harvard Medical School
Boston, MA|Boston, MA
Edip Gurol  
Massachusetts General Hospital|Harvard Medical School
Boston, MA|Boston, MA
Jonathan Polimeni  
Massachusetts General Hospital|Harvard Medical School
Boston, MA|Boston, MA
Steven Greenberg  
Massachusetts General Hospital|Harvard Medical School
Boston, MA|Boston, MA
Jingyuan Chen  
Massachusetts General Hospital|Harvard Medical School
Boston, MA|Boston, MA

Introduction:

Cerebral amyloid angiography (CAA) is a common age-related small vessel disease that can lead to reduced vascular reactivity. Visual stimulation has been shown to cause measurable differences in the fMRI response amplitude in the visual cortex in CAA patients compared to controls [1-4]. In this study, we employed high-resolution fMRI to investigate whether these differences in the hemodynamic response persist across all levels of the microvascular hierarchy within the visual cortex, assessed by sampling fMRI responses across cortical depths. Vascular changes elicited by both visual stimulation and hypercapnia were compared between CAA and healthy subjects.

Methods:

17 CAA subjects and 10 age-matched healthy controls (HCs) participated in this study. Data were collected on a 7T Siemens scanner with a custom-built 32-channel receive coil array. Visual paradigm (17 CAA, 10 HC): each subject underwent 1-3 scans of block-design visual stimuli (20/28 s on/off per block, 3-6 blocks per scan). BOLD-weighted fMRI data (1.1 mm iso. voxel size) were collected using two protocols: (a.) TR=2.4 s, 44 slices; (b.) TR=3.68 s, 126 slices. Hypercapnia paradigm (14 CAA, 7 HC) was implemented using medical air and 5% CO2. BOLD-weighted fMRI data (1.1 mm iso. voxel size) were collected using two protocols: (a.) TR=3 s, 102 slices; (b.) TR=3.68 s, 126 slices. Surface-based cortical depth estimation was performed using a high-res. T1-weighted anatomical data; the normalized cortical depth ('0': white matter; '100%': pial) of each voxel was computed according to its centroid coordinate [5]. Voxels were separated into 10 equispaced groups (from 0 to 200% depths; depths > 100% denote locations above the pial): D1-D10. Cortical-depth-dependent (CDD) vascular responses evoked by the visual stimuli (VRVIS): A standard GLM was used to identify task-active voxels. For each cortical depth, the mean elicited responses across all task-active voxels (with z-score > 2.3 and within the visual cortex [6]) were estimated. CDD vascular responses evoked by hypercapnia (VRCO2): VRCO2 within the visual mask (derived from the visual paradigm) were estimated for each subject. Given that hypercapnia was expected to cause a global vascular response, we additionally analyzed VRCO2 in white matter and a few gray-matter regions demonstrating high metabolic demand in the resting state.

Results:

We also observed reduced VRVIS in CAA subjects [1-4] (Fig. 1A). Results of different acquisitions (TR = 2.4/3.68 s) exhibited comparable timings and intensities, supporting the validity of integrating them for further comparisons. Overall, the CAA cohort showed reduced VRVIS across all cortical depths (Fig. 1B), consistent with the injury of small vessels in deeper cortex. Additionally, we noticed a more modest change in peak response intensities across depths in CAA (Fig. 1B, 'normalized by pial'). Two-sample t-tests of the normalized CDD intensity trends between groups yielded p-value = 0.0381(left hemisphere) and 0.0322 (right hemisphere).

VRCO2 did not reveal significant differences between HC and CAA cohorts in the occipital area (Fig. 2B), or in extensive gray matter and white matter regions investigated here (Fig. 2C). Collectively, these results suggest a smaller effect size or larger inter-subject variability of VRCO2 compared to VRVIS, which may be attributable to the dominating role of larger leptomeningeal arteries in driving hypercapnia-induced increases of blood flow.

Conclusions:

In summary, major findings of this study are two-fold: (1) we have shown that the CAA subjects demonstrated consistently reduced peak BOLD responses across cortical depths with an increasingly more pronounced difference near the pial surface; and (2) unlike neurogenic vascular responses, fMRI responses induced by CO2 inhalation were more consistent between the CAA and HC cohorts.

Disorders of the Nervous System:

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1

Modeling and Analysis Methods:

Activation (eg. BOLD task-fMRI)

Physiology, Metabolism and Neurotransmission :

Cerebral Metabolism and Hemodynamics 2

Keywords:

Aging
Cerebral Blood Flow
Cortical Layers
Data analysis
DISORDERS
HIGH FIELD MR
Modeling
Neurological

1|2Indicates the priority used for review
Supporting Image: Figure1.png
   ·Figure 1
Supporting Image: Figure2.png
   ·Figure 2
 

My abstract is being submitted as a Software Demonstration.

No

Please indicate below if your study was a "resting state" or "task-activation” study.

Task-activation

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Patients

Are you Internal Review Board (IRB) certified? Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.

Yes

Was any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Was any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Functional MRI
Structural MRI

For human MRI, what field strength scanner do you use?

7T

Which processing packages did you use for your study?

AFNI
SPM
FSL
Free Surfer

Provide references using author date format

[1] Dumas, A., Dierksen, G.A., Gurol, M.E., Halpin, A., Martinez‐Ramirez, S., Schwab, K., Rosand, J., Viswanathan, A., Salat, D.H., Polimeni, J.R. and Greenberg, S.M., 2012. Functional magnetic resonance imaging detection of vascular reactivity in cerebral amyloid angiopathy. Annals of neurology, 72(1), pp.76-81.
[2] Williams, R.J., Goodyear, B.G., Peca, S., McCreary, C.R., Frayne, R., Smith, E.E. and Pike, G.B., 2017. Identification of neurovascular changes associated with cerebral amyloid angiopathy from subject-specific hemodynamic response functions. Journal of Cerebral Blood Flow & Metabolism, 37(10), pp.3433-3445.
[3] van Harten T, Voigt S, Koemans E, van Opsta A, van Rooden S, van Buchem M, Terwindt G, Zwanenburg J, Walderveen M, van der Grond J, Wermer M, van Osch M. Vascular reactivity measured with high temporal resolution fMRI in hereditary and sporadic CAA. Annu Meet Organ Hum Brain Mapp. 2019:W465.
[4] Peca, S., McCreary, C.R., Donaldson, E., Kumarpillai, G., Shobha, N., Sanchez, K., Charlton, A., Steinback, C.D., Beaudin, A.E., Flück, D., Pillay, N., Fick GH., Poulin MJ, Frayne R, Goodyear BG, Smith EE, 2013. Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy. Neurology, 81(19), pp.1659-1665.
[5] Polimeni, J.R., Fischl, B., Greve, D.N. and Wald, L.L., 2010. Laminar analysis of 7 T BOLD using an imposed spatial activation pattern in human V1. Neuroimage, 52(4), pp.1334-1346.
[6] Yeo, B.T., Krienen, F.M., Sepulcre, J., Sabuncu, M.R., Lashkari, D., Hollinshead, M., Roffman, J.L., Smoller, J.W., Zöllei, L., Polimeni, J.R. and Fischl, B., 2011. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of neurophysiology.