Biology subjects

Chiarelli, A. M.

Publications and source records attributed to Chiarelli, A. M..

4 recordsLinked to original sources

bioRxiv2026

Human brain cortical oxygen consumption is positively related to soma surface area density.

Evidence from in-silico, ex vivo and invasive animal studies suggested the function of neural tissue to be inextricably linked to its structural and microstructural organization. However, this link has never been assessed non-invasively in humans. Here, we established a simple quantitative framework linking cerebral oxygen metabolism to gray matter microstructural features in healthy humans using advanced non-invasive MRI methods. The cerebral metabolic rate of oxygen consumption (CMRO2) was quantified with calibrated fMRI, whereas microstructural properties were estimated from diffusion MRI data fitted to the Soma and Neurite Density Imaging (SANDI) model, yielding soma radius (R soma) and soma volume fraction (fsoma) metrics, from which we derived maps of soma surface area density (SAD) and soma numerical density (ND) under the assumption of a spherical soma. CMRO2 was positively associated with SAD (r = 0.29, p < 0.01), fsoma (r = 0.28, p < 0.05) and ND (r = 0.25, p < 0.05), and negatively associated with Rsoma (r = -0.23, p < 0.05) across cortical brain regions. These relationships are consistent with predictions from experimental and theoretical studies, providing the first quantitative evidence that cerebral metabolic demand is coupled to microstructure in humans. The positive association of energy consumption with SAD is consistent with the notion that both the number of synapses (energy-demanding structures), and the energy required to maintain a membrane potential, scale with soma surface area. Our findings establish a non-invasive MRI framework for investigating the microstructural determinants of brain energy metabolism in health and potentially in disease.

neuroscience↗

bioRxiv2026

A comparison of continuous-wave fNIRS with quantitative fMRI-derived indices of brain function in the visual cortex

Functional near-infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI) both rely on the phenomenon of neurovascular coupling (NVC) to probe brain activity through their sensitivity to cerebral blood oxygenation. However, the relationship between fNIRS chromophores (oxy- and deoxyhaemoglobin, HbO and HbR), and fMRI (Blood Oxygen Level Dependent and Arterial Spin Labeling, BOLD and ASL) measurements, and whether this relationship remains consistent across subjects and physiological conditions, has only been partially characterised.. We acquired concurrent continuous-wave fNIRS and gradient-echo (GE) and spin-echo (SE) BOLD-ASL fMRI in healthy adults (n = 10) during visual stimulation. By applying calibrated fMRI methodology, we examined the relationships between fNIRS-derived haemoglobin modulations and fMRI-derived modulations in macrovascular (GE-) and microvascular (SE-) BOLD signals, cerebral blood flow (CBF), and oxygen metabolism (CMRO2). Group-level results showed strong temporal cross-modal agreement, with HbO and HbR tightly mirroring all fMRI signal time-courses (|r| > 0.8). A quantitative analysis of trial-by-trial modulations revealed distinct state-dependent behaviours: HbO maintained a stable relationship with the fMRI-derived metrics across conditions, whereas cross-modal relationships between HbR and fMRI-derived metrics substantially strengthened at higher flow-metabolism coupling (FMC), the ratio of CBF to CMRO2 change, an index of the strength of NVC. Both HbO and HbR were more strongly associated with GE-BOLD than with SE-BOLD. These findings provide a rigorous physiological grounding for fNIRS signal interpretation, demonstrating its utility as a surrogate marker for specific haemodynamic and metabolic parameters.

bioengineering↗

bioRxiv2025

Three-dimensional T1 mapping demonstrates the transfer of oxygen into cerebrospinal fluid during hyperoxia

BackgroundThis study optimised a non-invasive magnetic resonance imaging technique to investigate the transfer of oxygen into cerebrospinal fluid (CSF) across the whole brain of healthy subjects. MethodsA shortening of the T1 (longitudinal relaxation time) of CSF was induced by 100% hyperoxia and measured using a 3D SPACE sequence at 3T in 29 subjects, thereby demonstrating the diffusion of oxygen from blood to CSF. T1 mapping was performed at high resolution (0.9-mm isotropic, taking approximately 16 minutes) to capture anatomical details of the CSF spaces and was also repeated more rapidly at a lower resolution (3-mm isotropic, taking approximately 3.5 minutes) to capture the temporal dynamics of T1 changes. ResultsSignificant region-dependent reductions in T1 were observed, indicating increased oxygen concentration in CSF. These occurred most prominently and rapidly in the cortical subarachnoid space and basilar cisterns, stabilising between 7 and 10 minutes after initiating hyperoxia, suggesting that oxygen diffusion primarily occurs via pial arteries and arteries at the base of the skull, both of which are in proximity to CSF-filled spaces. Over a timescale of 16 minutes, smaller T1 changes, only observed on the high-resolution T1 maps, occurred in the posterior lateral ventricles, where the choroid plexus is found, and the cisterna magna, possibly because of mixing effects with the adjacent basilar cisterns. ConclusionsThis study provides insights into the structure of CSF and dynamics of blood-CSF oxygen exchange, including their regional dependence. Moreover, the methodology presented here could, in the future, offer a valuable tool for characterising the passive diffusion of oxygen across cerebral blood vessel walls (i.e., their oxygen permeability), thereby providing a potential marker of cerebrovascular integrity.

physiology↗

bioRxiv2021

Quantitative mapping of cerebral oxygen metabolism using breath-hold calibrated fMRI

Magnetic resonance imaging (MRI) offers the possibility to non-invasively map the rate of cerebral metabolic oxygen consumption (CMRO2), which is essential for understanding and monitoring neural function in both health and disease. Existing methods of mapping CMRO2, based on respiratory modulation of arterial spin labelling (ASL) and blood oxygen level dependent (BOLD) signals, require lengthy acquisitions and independent modulation of both arterial oxygen and carbon dioxide levels. Here, we present a new simplified method for mapping the rate of cerebral oxygen metabolism that can be performed using a simple breath-holding paradigm. The method incorporates flow-diffusion modelling of oxygen transport and physiological constraints to create a non-linear mapping between the maximum BOLD signal, M, baseline blood flow (CBF0), and CMRO2. A gradient boosted decision tree is used to learn this mapping directly from simulated MRI data. Modelling studies demonstrate that the proposed method is robust to variation in cerebral physiology and metabolism. This new gas-free methodology offers a rapid and pragmatic alternative to existing dual-calibrated methods, removing the need for specialist respiratory equipment and long acquisition times. In-vivo testing of the method, using an 8-minute 45 second protocol of repeated breath-holding, was performed on 15 healthy volunteers, producing quantitative maps of cerebral blood flow (CBF), oxygen extraction fraction (OEF), and CMRO2.

neuroscience↗