Spontaneous BOLD Signal Fluctuations in Young Healthy Subjects and Elderly Patients with Chronic Kidney Disease

Hesamoddin Jahanian,Manjula Kurella Tamura,Wendy W Ni,Thomas Christen,Michael E Moseley,Greg Zaharchuk,Yoko Hoshi

doi:10.1371/journal.pone.0092539

Hesamoddin Jahanian, Manjula Kurella Tamura + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0092539

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Journal: PloS one	Publication Date: Mar 20, 2014
Citations: 52	License type: CC BY 4.0

Affiliation: Stanford University

Abstract

Spontaneous fluctuations in blood oxygenation level-dependent (BOLD) images are the basis of resting-state fMRI and frequently used for functional connectivity studies. However, there may be intrinsic information in the amplitudes of these fluctuations. We investigated the possibility of using the amplitude of spontaneous BOLD signal fluctuations as a biomarker for cerebral vasomotor reactivity.We compared the coefficient of variation (CV) of the time series (defined as the temporal standard deviation of the time series divided by the mean signal intensity) in two populations: 1) Ten young healthy adults and 2) Ten hypertensive elderly subjects with chronic kidney disease (CKD).We found a statistically significant increase (P<0.01) in the CV values for the CKD patients compared with the young healthy adults in both gray matter (GM) and white matter (WM). The difference was independent of the exact segmentation method, became more significant after correcting for physiological signals using RETROICOR, and mainly arose from very low frequency components of the BOLD signal fluctuation (f<0.025 Hz). Furthermore, there was a strong relationship between WM and GM signal fluctuation CV's (R2 = 0.87) in individuals, with a ratio of about 1∶3.These results suggest that amplitude of the spontaneous BOLD signal fluctuations may be used to assess the cerebrovascular reactivity mechanisms and provide valuable information about variations with age and different disease states.

Highlights

Blood oxygenation level dependent (BOLD) is a complex signal arising from a combination of changes in cerebral blood volume (CBV), cerebral blood flow (CBF), and oxygen extraction fraction (OEF), leading to a change in the concentration of deoxyhemoglobin
The results of partial volume estimation (PVE) and strict threshold masking approaches are similar and are more significantly different compared to the standard template approach
Our results indicate a statistically significant increase in BOLD signal fluctuations in the chronic kidney disease (CKD) cohort and between GM and WM within each cohort

Summary

Introduction

Blood oxygenation level dependent (BOLD) is a complex signal arising from a combination of changes in cerebral blood volume (CBV), cerebral blood flow (CBF), and oxygen extraction fraction (OEF), leading to a change in the concentration of deoxyhemoglobin. Low frequency (f,0.1 Hz) spontaneous fluctuations in the BOLD signal have been observed in resting-state time series measurements [1] These fluctuations appear to be correlated in functionally connected brain regions and form the basis of restingstate fMRI studies [2,3,4]. The precise physiological origin of these signal fluctuations is not yet clear, they likely arise from oscillations in metabolic-linked brain physiology, arterial vasomotion, and hemodynamics [1,6,7], originating from myogenic and neurogenic sources [8]. They may be sensitive to disease states. Makedonov et al recently showed that the BOLD signal in white matter can be used as a biomarker for aging and small vessel disease [11]

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