Biology subjects

Clements, R. G.

Publications and source records attributed to Clements, R. G..

6 recordsLinked to original sources

bioRxiv2026

Iterative delay correction improves breath-hold cerebrovascular reactivity mapping in clinical populations

Cerebrovascular reactivity (CVR), the ability of cerebral blood vessels to dilate or constrict in response to a vasoactive stimulus, is an important measure of cerebrovascular health. Accurate CVR estimation requires accounting for the time required for the vasoactive stimulus to reach each brain region and the time it takes for local arterioles to modulate cerebral blood flow. The temporal search range used to calculate this spatially varying offset can substantially impact CVR estimates, and the appropriate search range may vary across populations, acquisition protocols, and even brain regions. Here, we present an iterative approach for automatically determining the appropriate maximum shift, using breath-hold fMRI data acquired in a cohort of stroke survivors. This approach selectively expands the delay search range only for voxels with estimated delays at the boundary (i.e., near the minimum or maximum shift) until the estimated delay is no longer constrained or a predefined value is reached. In the context of stroke, this approach significantly increased the number of voxels with statistically significant CVR among those initially at the boundary. It also resulted in CVR polarity reversals in voxels originally at the early-response boundary and amplified negative CVR values in voxels originally at the late-response boundary, suggesting that using an iterative maximum shift can critically impact CVR interpretation. This approach is broadly applicable beyond stroke, but careful parameter tuning is required, as illustrated by our demonstration of the parameter tuning process for a participant with Moyamoya disease. Together, these findings suggest that iterative delay correction allows for improved CVR assessments in clinical populations.

neuroscience↗

bioRxiv2026

Multi-echo BOLD fMRI improves cerebrovascular reactivity estimates in stroke

Cerebrovascular reactivity (CVR), the ability of cerebral blood vessels to dilate or constrict in response to a vasoactive stimulus, is a clinically meaningful measure of cerebrovascular health. Head motion and other noise sources substantially impact CVR quality, particularly in clinical populations. In this study, we evaluated multi-echo fMRI techniques, including optimal combination of echoes (ME-OC) and multi-echo independent component analysis (ME-ICA), for improving CVR quality relative to single-echo fMRI in participants with stroke. In a breath-hold fMRI dataset, ME-OC significantly improved CVR quality metrics and reduced the percentage of negative CVR values in normal-appearing gray and white matter (p<0.05). ME-ICA reduced the dependence of BOLD signals on head motion but did not improve CVR quality metrics. In a separate resting-state dataset, ME-OC effects were largely consistent with the breath-hold dataset, but ME-ICA also significantly improved CVR quality metrics and reduced negative CVR values in normal-appearing gray and white matter relative to ME-OC (p<0.05). These findings demonstrate that multi-echo fMRI can improve CVR estimation in clinical populations, particularly in low signal-to-noise datasets, enhancing the feasibility of CVR analyses in stroke studies and allowing for better visualization of stroke-related CVR deficits.

neuroscience↗

bioRxiv2025

Impact of multi-echo ICA modeling decisions on motor-task fMRI analysis

Multi-echo independent component analysis (ME-ICA) has been demonstrated to improve sensitivity and reliability of task functional magnetic resonance imaging (fMRI) data and, in particular, motor-task data with inherent task-correlated head motion. However, previous work has shown that an overly aggressive ME-ICA denoising approach may unintentionally remove task-related signal, while a more conservative approach may not effectively mitigate noise. While the effects of varied implementations of ME-ICA on signal and noise characteristics have been tested thoroughly in breath-hold data, the effects of similar modeling decisions have not been studied in motor-task data, which present with a more localized neural response. Here, we tested and compared the impacts of three analysis methods using rejected ME-ICA components as regressors in subject-level modeling: Aggressive (simple inclusion of ME-ICA regressors), Moderate (excluding task-correlated ME-ICA regressors from the model), and Conservative (orthogonalization of ME-ICA regressors to the core model and accepted ME-ICA components). We applied these methods to data from healthy and multiple sclerosis populations that included performance of hand-grasp, shoulder-abduction, and ankle-flexion tasks. We found that when the amount of head motion and its correlation with the task was high and the expected task-evoked signal was relatively low, the Conservative method led to significantly higher activation, t-statistics, and test-retest similarity in motor regions compared to the Aggressive method. Future motor-task studies may wish to implement similar models to prevent loss of motor signal, while still mitigating the effects of task-correlated head motion.

bioengineering↗

bioRxiv2024

Quantitative mapping of cerebrovascular reactivity amplitude and delay with breath-hold BOLD fMRI when end-tidal CO2 quality is low

Cerebrovascular reactivity (CVR), the ability of cerebral blood vessels to dilate or constrict in response to a vasoactive stimulus, is a clinically useful measure of cerebrovascular health. CVR is often measured using a breath-hold task to modulate blood CO2 levels during an fMRI scan. Measuring end-tidal CO2 (PETCO2) with a nasal cannula during the task allows CVR amplitude to be calculated in standard units (vascular response per unit change in CO2, or %BOLD/mmHg) and CVR delay to be calculated in seconds. The use of standard units allows for normative CVR ranges to be established and for CVR comparisons to be made across subjects and scan sessions. Although breath holding can be successfully performed by diverse patient populations, obtaining accurate PETCO2 measurements requires additional task compliance; specifically, participants must breathe exclusively through their nose and exhale immediately before and after each breath hold. Meeting these requirements is challenging, even in healthy participants, and this has limited the translational potential of breath-hold fMRI for CVR mapping. Previous work has focused on using alternative regressors such as respiration volume per time (RVT), derived from respiration-belt measurements, to map CVR. Because measuring RVT does not require additional task compliance from participants, it is a more feasible measure than PETCO2. However, using RVT does not produce CVR amplitude in standard units. In this work, we explored how to achieve CVR amplitude maps, in standard units, and CVR delay maps, when breath-hold task PETCO2 data quality is low. First, we evaluated whether RVT could be scaled to units of mmHg using a subset of PETCO2 data of sufficiently high quality. Second, we explored whether a PETCO2 timeseries predicted from RVT using deep learning allows for more accurate CVR measurements. Using a dense-mapping breath-hold fMRI dataset, we showed that both rescaled RVT and rescaled, predicted PETCO2 can be used to produce maps of CVR amplitude in standard units and CVR delay with strong absolute agreement to ground-truth maps. The rescaled, predicted PETCO2 regressor resulted in superior accuracy for both CVR amplitude and delay. In an individual with regions of increased CVR delay due to Moyamoya disease, the predicted PETCO2 regressor also provided greater sensitivity to pathology than RVT. Ultimately, this work will increase the clinical applicability of CVR in populations exhibiting decreased task compliance.

neuroscience↗

bioRxiv2024

Simultaneous cortical, subcortical, and brainstem mapping of sensory activation

Non-painful tactile sensory stimuli are processed in the cortex, subcortex, and brainstem. Recent functional magnetic resonance imaging (fMRI) studies have highlighted the value of whole-brain, systems-level investigation for examining pain processing. However, whole-brain fMRI studies are uncommon, in part due to challenges with signal to noise when studying the brainstem. Furthermore, the differentiation of small sensory brainstem structures such as the cuneate and gracile nuclei necessitates high resolution imaging. To address this gap in systems-level sensory investigation, we employed a whole-brain, multi-echo fMRI acquisition at 3T with multi-echo independent component analysis (ME-ICA) denoising and brainstem-specific modeling to enable detection of activation across the entire sensory system. In healthy participants, we examined patterns of activity in response to non-painful brushing of the right hand, left hand, and right foot, and found the expected lateralization, with distinct cortical and subcortical responses for upper and lower limb stimulation. At the brainstem level, we were able to differentiate the small, adjacent cuneate and gracile nuclei, corresponding to hand and foot stimulation respectively. Our findings demonstrate that simultaneous cortical, subcortical, and brainstem mapping at 3T could be a key tool to understand the sensory system in both healthy individuals and clinical cohorts with sensory deficits.

neuroscience↗

bioRxiv2023

Mechanical Property Based Brain Age Prediction using Convolutional Neural Networks

Brain age is a quantitative estimate to explain an individuals structural and functional brain measurements relative to the overall population and is particularly valuable in describing differences related to developmental or neurodegenerative pathology. Accurately inferring brain age from brain imaging data requires sophisticated models that capture the underlying age-related brain changes. Magnetic resonance elastography (MRE) is a phase contrast MRI technology that uses external palpations to measure brain mechanical properties. Mechanical property measures of viscoelastic shear stiffness and damping ratio have been found to change across the entire life span and to reflect brain health due to neurodegenerative diseases and even individual differences in cognitive function. Here we develop and train a multi-modal 3D convolutional neural network (CNN) to model the relationship between age and whole brain mechanical properties. After training, the network maps the measurements and other inputs to a brain age prediction. We found high performance using the 3D maps of various mechanical properties to predict brain age. Stiffness maps alone were able to predict ages of the test group subjects with a mean absolute error (MAE) of 3.76 years, which is comparable to single inputs of damping ratio (MAE: 3.82) and outperforms single input of volume (MAE: 4.60). Combining stiffness and volume in a multimodal approach performed the best, with an MAE of 3.60 years, whereas including damping ratio worsened model performance. Our results reflect previous MRE literature that had demonstrated that stiffness is more strongly related to chronological age than damping ratio. This machine learning model provides the first prediction of brain age from brain biomechanical data--an advancement towards sensitively describing brain integrity differences in individuals with neuropathology.

bioengineering↗