Metabolite Relaxation Times at 3T From Birth to 7 Years

Murali-Manohar, S.; Gad, A.; Shams, Z.; Simegn, G. L.; Song, Y.; Gudmundson, A. T.; Zo{square}llner, H. J.; Davies-Jenkins, C. W.; Simicic, D.; Yedavalli, V.; Gagoski, B.; Grant, E. P.; Dean, D. C.; Noeske, R.; Wisnowski, J. L.; Nebel, M. B.; Oeltzschner, G.; Edden, R. A. E.

doi:10.64898/2026.10.02.754450

bioRxiv · 10.64898/2026.10.02.754450

Metabolite Relaxation Times at 3T From Birth to 7 Years

Murali-Manohar, S.·Gad, A.·Shams, Z.·Simegn, G. L.·Song, Y.·Gudmundson, A. T.·Zo{square}llner, H. J.·Davies-Jenkins, C. W.·Simicic, D.·Yedavalli, V.·Gagoski, B.·Grant, E. P.·Dean, D. C.·Noeske, R.·Wisnowski, J. L.·Nebel, M. B.·Oeltzschner, G.·Edden, R. A. E.

View original source ↗Export metadata ↓

Abstract

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.

Explore related subjects

neuroscience Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Murali-Manohar, S., Gad, A., Shams, Z., Simegn, G. L., Song, Y., Gudmundson, A. T., Zo{square}llner, H. J., Davies-Jenkins, C. W., Simicic, D., Yedavalli, V., Gagoski, B., Grant, E. P., Dean, D. C., Noeske, R., Wisnowski, J. L., Nebel, M. B., Oeltzschner, G., Edden, R. A. E.. 2026-10-08. Metabolite Relaxation Times at 3T From Birth to 7 Years. https://doi.org/10.64898/2026.10.02.754450

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

KEEP EXPLORING

Related preprints

bioRxiv2026

EigenBrain maps cortical molecular architecture from functional, geometric, and structural eigenmodes

Neurotransmitter receptor and transporter distributions shape neural communication across the cortex and underpin mechanistic interpretations of brain function. Magnetic resonance imaging (MRI)-derived eigenmodes, low-dimensional spatial patterns that capture the principal axes of cortical organization, are increasingly used to reconstruct brain maps and offer a potential route to approximating molecular topographies in large cohorts where direct measurements are unavailable. Yet whether the type of MRI data used to derive these eigenmodes determines which receptor and transporter distributions can be approximated, and which molecular systems are accessible through this approach at all, remains unknown. Using a spatial reconstruction framework applied to 23 molecular systems spanning neurotransmitter, metabolic, and pathological markers, we show that eight receptor and transporter maps, spanning serotonin, dopamine, histamine, cholinergic, and opioid markers, can be selectively approximated from functional eigenmodes but not structural or geometric ones. This selectivity also reveals that functional brain organization encodes a specific subset of neuromodulatory topographies that structural and geometric organization does not. To illustrate translational potential in clinical cohorts where molecular imaging is unavailable, we applied individual-level eigenmode decompositions of MRI data projected onto the eight validated molecular systems and detected cross-sectional differences in autism and longitudinal changes in schizophrenia. Together, these findings reveal a difference in how geometric, structural, and functional brain organization relate to molecular architecture, offering a method for approximating validated molecular profiles in population neuroimaging cohorts that lack direct molecular imaging.

neuroscience↗

bioRxiv2026

Sex differences in fear extinction are conditional, not categorical

Threat memories are dynamic, and their behavioral expression can change with subsequent experience and the passage of time. Extinction training can reduce conditioned fear responses, yet these responses may re-emerge over time through spontaneous recovery. Although biological sex has been implicated as modulatory factor in fear and extinction memory processes, studies have reported inconsistent findings. Here, we investigated how differences in extinction training and the timing of memory assessment influence extinction memory in male and female mice. Using contextual fear conditioning, we assessed fear acquisition and threat retention, characterized within-session and across-session extinction during repeated training, and compared shorter (3-minute) and longer (6-minute) daily extinction sessions. We subsequently evaluated extinction memory retention and spontaneous recovery at a later time point. Estrous-cycle stage in females was monitored daily throughout the experimental protocol to examine its potential association with fear and extinction behavior. We found that males and females demonstrated comparable fear acquisition and threat memory, as well as similar extinction progression across days. During longer extinction sessions, but not shorter, males showed greater within-session reductions in freezing, whereas females exhibited modestly higher overall freezing. We found no significant sex difference in the magnitude of spontaneous recovery. There was no significant association between estrous-cycle stage and freezing behavior. Together, our findings suggest that sex-dependent differences in contextual fear extinction are not uniformly expressed, but rather depend on the experimental conditions under which extinction is assessed

neuroscience↗

bioRxiv2026

LAMA2-related muscular dystrophy alters Schwann cell calcium homeostasis and increases peripheral nerve inflammation

LAMA2-related muscular dystrophy (LAMA2-RD) affects skeletal muscle and peripheral nerves, yet the consequences of LAMA2 deficiency on peripheral nerve integrity beyond early postnatal development remain incompletely understood. We investigated sciatic nerve architecture and molecular alterations across postnatal life in hypomorphic Lama2dy2J/dy2J mice. LAMA2 localizes around the abaxonal surface of myelinating Schwann cells in control nerves. LAMA2-deficient nerves exhibited patchy regions lacking myelinated axons from early postnatal stages into adulthood, including expanded Remak bundles along with axons completely lacking normal Schwann cell ensheathment. In adult nerves, myelin infolding and reduced myelin circularity revealed abnormalities in the architecture of myelin that had formed. Bulk sciatic nerve RNA sequencing identified altered calcium-signaling and immune-related transcriptional signatures. Complementary Fura Red measurements in primary nerve-derived Schwann cell cultures demonstrated decreased intracellular calcium in LAMA2-deficient samples, while ATP-evoked responses were preserved. Older LAMA2-deficient nerves also exhibited increased CD45+CD11b+ myeloid-cell infiltration. Together, these observations extend the characterization of LAMA2-associated neuropathy into adulthood and identify calcium homeostasis and neuroimmune responses as candidate processes relevant to persistent peripheral nerve pathology.

neuroscience↗