bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.09.07.506917

On the performance of multi-compartment relaxometry for myelin water imaging - Intra-subject and inter-protocol reproducibility

Chan, K.-S.·Chamberland, M.·Marques, J. P.
View original source ↗Export metadata ↓

Abstract

We evaluate the test-retest repeatability and study the tissue properties of multicompartment relaxometry-based myelin water imaging (MCR-MWI) derived from different gradient echo (GRE) acquisition settings. Additionally, the variable flip angle acquisition scheme is optimised based on numerical simulations to reduce the acquisition time of MCR-MWI in a clinically practical range without using advanced image acquisition methods. For the test-retest analysis, in vivo imaging was performed to collect data from three healthy volunteers in two identical sessions. Three GRE sequence settings with different echo times and repetition times imitating various scanner setups were evaluated. The in vivo data was also used to validate the optimal variable flip angle combination derived from simulations. Bundle-specific profiles of MCR-MWI derived microstructural parameters were investigated, as well as the cross-correlations of those parameters. Good cross-session repeatability is observed for MCR-MWI. While good correlations can also be found in myelin water fraction (MWF) across protocols, systematic differences, particularly for protocols with different repetition times, are observed. Numerical simulations indicate that MCR-MWI can be performed with a minimum of three flip angles covering a wide range of T1 weighting without adding significant measurement bias and the result is supported by the in vivo experiment allowing whole brain 1.5mm isotropic MWF maps to be acquired in 9 minutes. Bundles-specific MWF analysis reveals that certain white matter bundles are similar in all three participants. We also found that microstructure relaxation parameters have low correlations with MWF. MCR-MWI is a reproducible measure of myelin. However, attention should be paid to considering the protocol related MWF differences for comparison studies, especially when different repetition times are used as this can introduce biases up to 0.5% of MWF in our tested protocols. The optimised flip angle acquisition scheme can reduce the total scan time to 40% of the original implementation without significant quality degradation. Highlights- Multi-compartment relaxometry based myelin water imaging (MCR-MWI) can be performed with data comprising as few as 3 flip angles without introducing substantial bias or instability in the fitting procedure; - MCR-MWI is a reproducible measure of myelin water fraction (MWF) and incorporating DWI can further improve the measurement reproducibility; - MCR-MWI allows the acquisition of whole brain 1.5mm isotropic MWF maps in 9 minutes, even without the use of advanced model-based reconstructions; - Small MWF bias can present in cross-protocol comparison if the MT effect is not constant across GRE protocols (e.g., different TRs or flip angle combinations); - Compartmental relaxation parameters derived from MCR-MWI possess complimentary information beyond myelin water concentration.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Chan, K.-S., Chamberland, M., Marques, J. P.. 2022-09-08. On the performance of multi-compartment relaxometry for myelin water imaging - Intra-subject and inter-protocol reproducibility. https://doi.org/10.1101/2022.09.07.506917

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗
bioRxiv2026

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗
bioRxiv2026

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗