Dataset Information

Blood-brain barrier water exchange measurements using FEXI: Impact of modeling paradigm and relaxation time effects.

ABSTRACT:

Purpose

To evaluate potential modeling paradigms and the impact of relaxation time effects on human blood-brain barrier (BBB) water exchange measurements using FEXI (BBB-FEXI), and to quantify the accuracy, precision, and repeatability of BBB-FEXI exchange rate estimates at 3 T$$ \mathrm{T} $$ .

Methods

Three modeling paradigms were evaluated: (i) the apparent exchange rate (AXR) model; (ii) a two-compartment model ( 2CM$$ 2\mathrm{CM} $$ ) explicitly representing intra- and extravascular signal components, and (iii) a two-compartment model additionally accounting for finite compartmental T1$$ {\mathrm{T}}_1 $$ and T2$$ {\mathrm{T}}_2 $$ relaxation times ( 2CMr$$ 2{\mathrm{CM}}_r $$ ). Each model had three free parameters. Simulations quantified biases introduced by the assumption of infinite relaxation times in the AXR and 2CM$$ 2\mathrm{CM} $$ models, as well as the accuracy and precision of all three models. The scan-rescan repeatability of all paradigms was quantified for the first time in vivo in 10 healthy volunteers (age range 23-52 years; five female).

Results

The assumption of infinite relaxation times yielded exchange rate errors in simulations up to 42%/14% in the AXR/ 2CM$$ 2\mathrm{CM} $$ models, respectively. Accuracy was highest in the compartmental models; precision was best in the AXR model. Scan-rescan repeatability in vivo was good for all models, with negligible bias and repeatability coefficients in grey matter of RCAXR=0.43$$ {\mathrm{RC}}_{\mathrm{AXR}}=0.43 $$ s-1$$ {\mathrm{s}}^{-1} $$ , RC2CM=0.51$$ {\mathrm{RC}}_{2\mathrm{CM}}=0.51 $$ s-1$$ {\mathrm{s}}^{-1} $$ , and RC2CMr=0.61$$ {\mathrm{RC}}_{2{\mathrm{CM}}_r}=0.61 $$ s-1$$ {\mathrm{s}}^{-1} $$ .

Conclusion

Compartmental modelling of BBB-FEXI signals can provide accurate and repeatable measurements of BBB water exchange; however, relaxation time and partial volume effects may cause model-dependent biases.

SUBMITTER: Powell E

PROVIDER: S-EPMC10962589 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Blood-brain barrier water exchange measurements using FEXI: Impact of modeling paradigm and relaxation time effects.

Powell Elizabeth E Ohene Yolanda Y Battiston Marco M Dickie Ben R BR Parkes Laura M LM Parker Geoff J M GJM

Magnetic resonance in medicine 20230309 1

<h4>Purpose</h4>To evaluate potential modeling paradigms and the impact of relaxation time effects on human blood-brain barrier (BBB) water exchange measurements using FEXI (BBB-FEXI), and to quantify the accuracy, precision, and repeatability of BBB-FEXI exchange rate estimates at 3 T $$ \mathrm{T} $$ .<h4>Methods</h4>Three modeling paradigms were evaluated: (i) the apparent exchange rate (AXR) model; (ii) a two-compartment model ( 2 CM $$ 2\mathrm{CM} $$ ) explicitly representing intra- a ...[more]

PMID: 36892973

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Project description:Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and heterozygous HTRA1 mutation-related cerebral small vessel disease (CSVD) are the two types of dominant hereditary CSVD. Blood-brain barrier (BBB) failure has been hypothesized in the pathophysiology of CSVD. However, it is unclear whether there is BBB damage in the two types of hereditary CSVD, especially in heterozygous HTRA1 mutation-related CSVD. In this study, a case-control design was used with two disease groups including CADASIL (n = 24), heterozygous HTRA1 mutation-related CSVD (n = 9) and healthy controls (n = 24). All participants underwent clinical cognitive assessments and brain MRI. Diffusion-prepared pseudo-continuous arterial spin labelling was used to estimate the water exchange rate across the BBB (kw). Correlation and multiple linear regression analyses were used to examine the association between kw and disease burden and neuropsychological performance, respectively. Compared with the healthy controls, kw in the whole brain and multiple brain regions was decreased in both CADASIL and heterozygous HTRA1 mutation-related CSVD patients (Bonferroni-corrected P < 0.007). In the CADASIL group, decreased kw in the whole brain (β = -0.634, P = 0.001), normal-appearing white matter (β = -0.599, P = 0.002) and temporal lobe (β = -0.654, P = 0.001) was significantly associated with higher CSVD score after adjusting for age and sex. Reduced kw in the whole brain was significantly associated with poorer neuropsychological performance after adjusting for age, sex and education in both CADASIL and heterozygous HTRA1 mutation-related CSVD groups (β = 0.458, P = 0.001; β = 0.884, P = 0.008). This study showed that there was decreased water exchange rate across the BBB in both CADASIL and heterozygous HTRA1 mutation-related CSVD patients, suggesting a common pathophysiological mechanism underlying the two types of hereditary CSVD. These results highlight the potential use of kw for monitoring the course of CADASIL and heterozygous HTRA1 mutation-related CSVD, a possibility which should be tested in future research.

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Dataset Information

Blood-brain barrier water exchange measurements using FEXI: Impact of modeling paradigm and relaxation time effects.

Purpose

Methods

Results

Conclusion

Publications

Blood-brain barrier water exchange measurements using FEXI: Impact of modeling paradigm and relaxation time effects.

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