Molecular-enriched functional connectivity in the human brain using multiband multi-echo simultaneous ASL/BOLD fMRI

Abstract

Receptor-Enriched Analysis of functional Connectivity by Targets (REACT) is a novel analytical strategy that enriches functional connectivity (FC) information from functional MRI (fMRI) with molecular information on the neurotransmitter distribution density in the human brain, providing a biological basis to the FC analysis. So far, this integrative approach has been used in blood oxygen level-dependent (BOLD) fMRI studies only, providing new insights into the brain mechanisms underlying specific disorders and its response to pharmacological challenges. In this study, we demonstrate that the application of REACT can be further extended to arterial spin labelling (ASL) fMRI. Some of the advantages of this extension include the combination of neurotransmitter specific information provided by molecular imaging with a quantitative marker of neuronal activity, the suitability of ASL for pharmacological MRI (phMRI) studies assessing drug effects on baseline brain function, and the possibility to acquire images that are not affected by susceptibility artifacts in the regions linked to major neurotransmitter systems.In this work, we tested the feasibility of applying REACT to resting state ASL fMRI and compared the molecular-enriched FC maps derived from ASL data with those derived from BOLD data. We applied REACT to high-resolution, whole-brain simultaneous ASL/BOLD resting-state fMRI data of 29 healthy subjects and estimated the ASL- and BOLD-based FC maps related to six molecular systems, including the transporters of dopamine, noradrenaline, serotonin and vesicular acetylcholine, and the GABA-A and mGlu5 receptors. We then compared the ASL and BOLD FC maps in terms of spatial similarity, using the Dice Similarity Index and the voxel-wise spatial correlation. On a data subsample (N=19) we also evaluated the test-retest reproducibility of each modality using the regional intraclass correlation coefficient, and compared the two modalities.Our results showed robust spatial patterns of molecular-enriched functional connectivity for both modalities, moderate to high similarity between BOLD- and ASL-derived FC maps and mixed results in terms of reproducibility (i.e., none of the modalities outperformed the other). Overall, our findings show that the ASL signal is as informative as BOLD in detecting functional circuits associated with specific molecular pathways, and that the two modalities may provide complementary information related to these circuits.Considering the more direct link of ASL imaging with neuronal acrivity compared to BOLD and its suitability for phMRI studies, this new integrative approach could become a valuable asset in clinical studies investigating functional alterations in patients with brain disorders, or in pharmacological studies investigating the effects of new or existing compounds on the brain.

Denoising task-correlated head motion from motor-task fMRI data with multi-echo ICA

“…We investigated the within-subject similarity of activation estimates by examining the voxel-wise spatial correlation between the Limited and Amplified motion scans for each subject. Spatial correlation has been used by several fMRI studies as a metric of similarity and stability across scans (Braban et al, 2023;Dipasquale et al, 2023;Gong et al, 2023;Kannurpatti et al, 2012;Yuan et al, 2013). The Limited motion scan for each subject served as an estimate of the groundtruth activation in our dataset.…”

Abnormal Glutamatergic and Serotonergic Connectivity in Visual Snow Syndrome and Migraine with Aura

“…Running REACT comprises of a 2‐step multiple linear regression analysis within the REACT toolbox (https://github.com/ottaviadipasquale/react-fmri). 41 The 4D whole‐brain fMRI maps and PET maps were demeaned, and the PET maps used as spatial regressors to estimate the dominant BOLD fluctuations related to each of the molecular targets. Of note, a mask, generated by binarizing the PET maps, was used to restrict analysis to only the areas where information on transporter and receptor density was available.…”

Neurotransmitter receptor densities are associated with changes in regional Cerebral blood flow during clinical ongoing pain

“…To overcome limitations posed by on‐site PET acquisition, exploitation of binding potential (BPnd) templates from individual PET studies has become increasingly popular to inform neurotransmitter related activity, assuming its magnitude to be a linear function of receptor spatial distribution and availability across brain regions (Sander et al, 2020 ). This approach has been efficiently used in other fields of neuroimaging to map functional haemodynamic activation induced by different compounds onto distributions of their relevant target receptors (Dipasquale et al, 2019 ; Dipasquale et al, 2022 ; Dukart et al, 2018 ; Lawn et al, 2022 ; Selvaggi et al, 2019 ).…”