Biology subjects

Dean, D. C.

Publications and source records attributed to Dean, D. C..

5 recordsLinked to original sources

bioRxiv2026

Metabolite Relaxation Times at 3T From Birth to 7 Years

PurposeWith growing interest in pediatric MRS to understand the neurochemistry of brain development, it is essential to establish pediatric-specific metabolite T1 and T2 relaxation times for reliable quantification of metabolites. Furthermore, characterization of age-related changes in relaxation times may provide insight into developmental differences in tissue microstructure and cellular composition. Therefore, the goals of this study were two-fold: (1) to estimate metabolite T1 and T2 relaxation times in a pediatric cohort; and (2) to assess linear relationships between age and relaxation times. MethodsTI- and TE-series data were acquired from the bilateral thalamus in 20 and 25 participants aged between 0 and 7 years, respectively. Data were processed and modelled in Osprey 2.5.0. Metabolite T1 and T2 relaxation times of total N-acetylaspartate at 2.0 ppm (tNAA2.0), total creatine at 3.0 ppm (tCr3.0), total creatine at 3.9 ppm (tCr3.9), total choline (tCho), myo-inositol (mI) and the combined glutamate and glutamine (Glx) were estimated by fitting the modelled signal amplitudes to TI-series inversion recovery signal and TE-series exponential decay equations, respectively. Linear relationships with age were tested for metabolite T1 and T2 relaxation times using Spearman correlations. ResultstNAA2.0 and Glx showed significant changes in T1 with age. tNAA2.0, tCr3.0, tCho and mI showed significant decrease in T2 with age. ConclusionSeveral metabolites showed significant changes in relaxation times with age in the thalamus region. Therefore, use of age-specific relaxation correction for pediatric studies using the linear equations provided is encouraged for reliable quantification of metabolites.

neuroscience↗

bioRxiv2026

Age-related differences in neurometabolite concentrations during early infancy: A cross-sectional analysis of the HBCD Release 1.0

Background: Developmental trajectories of low-concentration neurometabolites such as the neurotransmitter {gamma}-aminobutyric acid (GABA), and the antioxidants glutathione (GSH) and ascorbate (Asc) across early infancy remain unexplored. Advances in spectral editing enabled the measurement of these key molecules together with high-concentration metabolites like N-acetylaspartate (NAA) and glutamate (Glu) in the HEALthy Brain and Child Development (HBCD) study, the largest longitudinal study of early brain development in the United States. Purpose: To determine the age-associated trajectories of 14 key neurometabolites during early infancy from a cross-sectional 1H-MRS dataset. Materials and Methods: HBCD utilizes ISTHMUS, an integrated MRS sequence that includes both an unedited short-echo-time PRESS acquisition and an advanced 4-step Hadamard-encoded sequence, HERCULES to enable measurement of both high- and low-concentration metabolites. Metabolite quantification was carried out by the HBCD Data Coordinating Center (HDCC) using an automated Osprey pipeline, with data from 201 infants ages 0 - 10 weeks adjusted age included in the tabular imaging results in HBCD data release 1.0. After excluding preterm born infants and data with poor linewidth or model quality metric, we tested for linear associations with adjusted age for each metabolite. Results: Concentration estimates of total NAA (tNAA), total creatine (tCr) and glutamate (Glu) as well as the combined sum of glutamate and glutamine (Glx) significantly increased across ages 0 - 10 weeks, while myo-inositol (mI) decreased. GABA and GSH showed age-related trends, but did not reach significance. Levels of the lipid precursor phosphorylethanolamine (PE) and Asc are higher in the first months than established adult values. Conclusion: Multiple metabolites showed significant age-related changes during early infancy. While GABA and GSH did not, future work will establish whether the trends suggested here contribute to linear or non-linear patterns across the first years of life.

neuroscience↗

bioRxiv2025

Cellular deconvolution of the brain with topological magnetic resonance image analysis

Magnetic resonance imaging (MRI) is foundational tool in neuroscience, enabling characterization of neuroanatomical markers of disease, behavior, and cognition. However, the precise cellular processes driving the structural and functional readouts provided by MRI remain opaque. Non-invasively assessing cell type, abundance, and location using MRI has the potential to revolutionize both basic science and clinical practice. To this end, we developed SpaTial Representation and Analysis using Topological Architecture (STRATA), an image-based gradient-boosted machine learning framework, which quantifies cell type proportions of neurons, astrocytes, oligodendrocytes, and microglia from MR images. Here we demonstrate and validate STRATA on diverse disease models, species, and regions of interest that together highlight the generalizability of the STRATA framework.

neuroscience↗

bioRxiv2024

A Water Relaxation Atlas for Age and Region specific Metabolite Concentration Correction

Metabolite concentration estimates from Magnetic Resonance Spectroscopy (MRS) are typically quantified using water referencing, correcting for relaxation-time differences between metabolites and water. One common approach is to correct the water reference signal for differential relaxation within three tissue compartments (gray matter, white matter, and cerebrospinal fluid) using fixed literature values. However, water relaxation times (T1 and T2) vary between brain locations, in pathology, and with age. MRS studies, even those measuring metabolite levels across the lifespan, often ignore these effects, because of a lack of reference data. The purpose of this study is to develop a water relaxometry atlas and to integrate location- and age-appropriate relaxation values into the MRS analysis workflow. 101 volunteers (51 men, 50 women; [~]10 male and 10 female participants per decade (from the 20s to 60s), were recruited. T1-weighted MPRAGE images ((1-mm)3 isotropic resolution) were acquired. Whole-brain water T1 and T2 measurements were made with DESPOT ((1.4 mm)3 isotropic resolution). T1 and T2 maps were registered to the JHU MNI-SS/EVE atlas using affine and LDDMM transformation. The atlass 268 parcels were reduced to 130 by combining homologous parcels. Mean T1 and T2 values were calculated for each parcel in each subject. Linear models of T1 and T2 as functions of age were computed, using age - 30 as the predictor. Reference atlases of "age-30-intercept" and age-slope for T1 and T2 were generated. The atlas-based workflow was integrated into Osprey, which co-registers MRS voxels to the atlas and calculates location- and age-appropriate water relaxation parameters for quantification. The water relaxation aging atlas revealed significant regional and tissue differences in water relaxation behavior across adulthood. Using location- and subject-appropriate reference values in the MRS analysis workflow removes a current methodological limitation and is expected to reduce quantification biases associated with water-referenced tissue correction, especially for studies of aging.

neuroscience↗

bioRxiv2024

Comparison of test-retest reproducibility of DESPOT and 3D-QALAS for water T1 and T2 mapping

PurposeRelaxometry, specifically T1 and T2 mapping, has become an essential technique for assessing the properties of biological tissues related to various physiological and pathological conditions. Many techniques are being used to estimate T1 and T2 relaxation times, ranging from the traditional inversion or saturation recovery and spin-echo sequences to more advanced methods. Choosing the appropriate method for a specific application is critical since the precision and accuracy of T1 and T2 measurements are influenced by a variety of factors including the pulse sequence and its parameters, the inherent properties of the tissue being examined, the MRI hardware, and the image reconstruction. The aim of this study is to evaluate and compare the test-retest reproducibility of two advanced MRI relaxometry techniques (Driven Equilibrium Single Pulse Observation of T1 and T2, DESPOT, and 3D Quantification using an interleaved Look-Locker acquisition Sequence with a T2 preparation pulse, QALAS), for T1 and T2 mapping in a healthy volunteer cohort. Methods10 healthy volunteers underwent brain MRI at 1.3 mm3 isotropic resolution, acquiring DESPOT and QALAS data ([~]11.8 and [~]5 minutes duration, including field maps, respectively), test-retest with subject repositioning, on a 3.0 Tesla Philips Ingenia Elition scanner. To reconstruct the T1 and T2 maps, we used an equation-based algorithm for DESPOT and a dictionary-based algorithm that incorporates inversion efficiency and B1-field inhomogeneity for QALAS. The test-retest reproducibility was assessed using the coefficient of variation (CoV), intraclass correlation coefficient (ICC) and Bland-Altman plots. ResultsOur results indicate that both the DESPOT and QALAS techniques demonstrate good levels of test-retest reproducibility for T1 and T2 mapping across the brain. Higher whole-brain voxel-to-voxel ICCs are observed in QALAS for T1 (0.84 {+/-} 0.039) and in DESPOT for T2 (0.897 {+/-} 0.029). The Bland-Altman plots show smaller bias and variability of T1 estimates for QALAS (mean of -0.02 s, and upper and lower limits of -0.14 and 0.11 s, 95% CI) than for DESPOT (mean of -0.02 s, and limits of -0.31 and 0.27 s). QALAS also showed less variability (mean 1.08 ms, limits -1.88 to 4.04 ms) for T2 compared to DESPOT (mean of 2.56 ms, and limits -17.29 to 22.41 ms). The within-subject CoVs for QALAS range from 0.6% (T2 in CSF) to 5.8% (T2 in GM), while for DESPOT they range from 2.1% (T2 in CSF) to 6.7% (T2 in GM). The between-subject CoVs for QALAS range from 2.5% (T2 in GM) to 12% (T2 in CSF), and for DESPOT they range from 3.7% (T2 in WM) to 9.3% (T2 in CSF). ConclusionOverall, QALAS demonstrated better reproducibility for T1 and T2 measurements than DESPOT, in addition to reduced acquisition time.

neuroscience↗