Accounting for the role of hematocrit in between‐subject variations of MRI‐derived baseline cerebral hemodynamic parameters and functional BOLD responses

Abstract

Baseline hematocrit fraction (Hct) is a determinant for baseline cerebral blood flow (CBF) and between-subject variation of Hct thus causes variation in task-based BOLD fMRI signal changes. We first verified in healthy volunteers (n 5 12) that Hct values can be derived reliably from venous blood T 1 values by comparison with the conventional lab test. Together with CBF measured using phase-contrast MRI, this noninvasive estimation of Hct, instead of using a population-averaged Hct value, enabled more individual determination of oxygen delivery (DO 2 ), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ). The inverse correlation of CBF and Hct explained about 80% of between-subject variation of CBF in this relatively uniform cohort of subjects, as expected based on the regulation of DO 2 to maintain constant CMRO 2 . Furthermore, we compared the relationships of visual task-evoked BOLD response with Hct and CBF. We showed that Hct and CBF contributed 22%-33% of variance in BOLD signal and removing the positive correlation with Hct and negative correlation with CBF allowed normalization of BOLD signal with 16%-22% lower variability. The results of this study suggest that adjustment for Hct effects is useful for studies of MRI perfusion and BOLD fMRI. Hum Brain Mapp 39:344-353, 2018.V C 2017 Wiley Periodicals, Inc.

Individual differences in haemoglobin concentration influence BOLD fMRI functional connectivity and its correlation with cognition

“…The results suggest that it is possible that previous studies of sex differences in functional connectivity that did not control for haemoglobin may be confounded, at least in ageing (e.g., Jamadar et al, 2018). Our results are consistent with some (Xu et al;Guensch et al, 2016), but not other (Yang et al) results in healthy younger adults. Given the differences in haemoglobin concentration over the lifespan (Backman et al 2016, Cruikshank, 1970Salive et al, 1992), future studies should explore if the effect of haemoglobin on the BOLD-fMRI signal varies with age.…”

“…The current sample is substantially larger than the previous studies of the influence of haemoglobin on BOLD-fMRI measures (Yang et al, 2015;Xu et al, 2018), with a sample size of 518 subjects. Like Xu et al (2018) our results suggest that individual differences in haemoglobin have a substantial influence on BOLD-fMRI measures of functional connectivity and functional connectivity-cognition relationships. In contrast to Yang et al (2015), we found that haemoglobin effects were widespread, spatially non-specific in men;…”

“…In another sample of 13 healthy middle-aged (mean age 35yrs; s.d. 7) adults, Xu et al (2018) found that 22% (i.e., R 2 =0.22) of the inter-subject variability of the BOLD response in the visual cortex to flickering checkerboard stimulus was associated with haematocrit, consistent with previous studies of haematocrit and the BOLD signal (R 2 =0.23; Gustard et al, 2003; R 2 =0.28, Levin et al, 2001). When the BOLD response was normalised by the haematocrit, the BOLD signal coefficient of variation reduced by 16% leading Xu et al (2018) to conclude that normalisation of the BOLD signal by individual haematocrit levels is an important step for enhancing the detection power of BOLD-fMRI studies.…”

“…This source of variability in BOLD signal (and SNR) across subjects has the potential to influence measures of functional connectivity, particularly for analyses that examine individual FC variability and differences between groups of individuals. In fact, inter-subject variation in haematocrit has been found to correlate with the degree of centrality of fMRI networks (Yang et al, 2015), and to mediate the magnitude of the BOLD response in the visual cortex (Xu et al, 2018).…”

MRI‐based measurements of whole‐brain global cerebral blood flow: Comparison and validation at 1.5T and 3T

“…This finding is in good agreement with the report of Vernooij et al 6 It is well known that hematocrit fraction is a crucial determinant of CBF, and there exists an inverse relationship between hematocrit and CBF. 39 The normal hematocrit level ranges from 40-54% and from 36-48% for men and women, respectively. 40 The wide range of Hct among subjects may explain the larger intersubject variation of CBF.…”