Biology subjects

Cudalbu, C.

Publications and source records attributed to Cudalbu, C..

7 recordsLinked to original sources

bioRxiv2026

Impacts of retrospective lipid suppression on metabolite quantification in preclinical proton MR spectroscopic imaging

Extracranial lipid contamination remains a challenge in proton magnetic resonance spectroscopic imaging (MRSI), especially in short acquisition delay MRSI, where broad lipid resonances overlap with metabolite and macromolecular signals. Although retrospective lipid suppression techniques are widely used in human MRSI, their effects on metabolite quantification in preclinical MRSI, which is more prone to lipid contamination, have not yet been examined. In this study, we assessed how the retrospective lipid suppression and spectral fitting range influence spectral quality, spatial metabolite mapping, and quantification variability using proton MRSI of rat brains at 14.1 T. Lipid suppression was applied via an orthogonal projection method to both fully sampled and compressed sensing datasets, each comprising data with minimal and pronounced lipid contamination. Spectral fitting was performed with both broad (4.1 - 0.2 ppm) and narrow (4.1 - 1.8 ppm) ranges. When lipid contamination was minimal, suppression caused only slight spectral and spatial changes, with consistent metabolite quantification across conditions. In contrast, datasets with pronounced lipid contamination exhibited notable spectral changes following suppression, consequently affecting spatial metabolite mapping and concentration estimates. Group analysis revealed that metabolites with low concentration estimates were most affected. Similar effects were observed in compressed sensing datasets. Our results provide a better understanding of the impact of retrospective lipid suppression on metabolite quantification in preclinical MRSI, thereby supporting future optimizations for its effective application.

neuroscience↗

bioRxiv2025

MRS4Brain: a processing toolbox for preclinical MR spectroscopy and spectroscopic imaging data

ObjectivesMagnetic resonance spectroscopy is a non-invasive technique for probing metabolism and underpins advanced methods such as magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted spectroscopy (DWS). MRSI enables spatial mapping of metabolite distributions, offering insights into regional metabolic heterogeneity that single-voxel spectroscopy (SVS) cannot capture. However, MRSI produces large multidimensional datasets and requires complex processing pipelines, limiting reproducibility and accessibility. While human studies benefit from advanced processing tools, similar developments in preclinical research remain scarce, highlighting a demand for practical tools accessible to non-experts. MethodsTo address this need, we introduce the MRS4Brain Toolbox, a freely available MATLAB-based platform for preclinical spectroscopy, including MRSI, SVS, and DWS. ResultsThe toolbox integrates reconstruction, preprocessing, quantification, quality control, brain segmentation automatically overlaid on metabolite maps, modeling, and statistical analysis into unified workflows accessible via a graphical interface. ConclusionBy streamlining data processing and reducing technical barriers, MRS4Brain Toolbox promotes reproducibility, harmonization, and broader adoption of advanced spectroscopic techniques in preclinical studies, ultimately facilitating translational research.

neuroscience↗

bioRxiv2025

Metabolic modelling and time-resolved mapping of glucose oxidative metabolism in rats brain by indirect deuterium detection with 1H-FID-MRSI at 9.4T

ObjectThe present study exploits newly developed dynamic indirect 1H-[2H]-FID-MRSI at 9.4T, combined with a dedicated metabolic model, to enable regional and quantitative characterization of glucose oxidative metabolism flux in the rat brain with minimal metabolic assumptions, by measuring both 2H-labelled Glx turnover and pool size along a controlled 2H-Glc infusion protocol. Materials and MethodsSeven rats underwent dynamic 2D 1H-FID-MRSI during a 2-hour infusion of [6,6-2H2] glucose. Consecutive 13-min acquisitions quantified Glx-C4 1H-signal decay, converted to 2H-Glx concentrations using baseline metabolite pool sizes. A three-pool kinetic model including 2H-label loss was fitted to regional turnover curves to estimate oxidative flux (Vgt) and pyruvate dilution (Kdil). Model performance and parameter robustness were finally assessed with Monte-Carlo simulations. ResultsIn vivo 2H-Glx turnover showed a saturated exponential rise ([~]60 min), with a labelling plateau higher in striatum (1.85 mol/g) than hippocampus (1.55 mol/g). Metabolic modelling provided region-specific oxidative fluxes: Vgt = 0.27 {+/-} 0.07 mol/g/min (hippocampus) and Vgt = 0.40 {+/-} 0.06 mol/g/min (striatum), with consistent Kdil across regions. Simulations confirmed a good model robustness in retrieving Vgt over a large range of experimental conditions. DiscussionThis work shows the appropriateness of indirect dynamic 1H-[2H]-FID-MRSI for quantitative metabolic flux mapping of cerebral glucose oxidative metabolism.

neuroscience↗

bioRxiv2025

Towards harmonized spectral quantification in MRSI: Comparative analysis of Backward-Linear-Predicted and original 1H-FID-MRSI dephased data

ObjectWe hypothesized that the inherent acquisition delay (AD) in {superscript 1}H-FID-MRSI can introduce systematic LCModel quantification biases due to strong spectral dephasing, and that Backward-Linear-Prediction (BLP) reconstruction toward AD = 0 ms can harmonize metabolite estimates across acquisitions with various delays. Materials and Methods2D {superscript 1}H-FID-MRSI were acquired in rats at 14.1T with three AD values (0.71, 0.94, 1.30 ms). Hippocampal metabolites were quantified using LCModel and AD-matched basis sets. Complementary Monte-Carlo simulations (n = 1000) replicated {superscript 1}H-FID-MRSI spectra at multiple ADs under realistic SNR conditions. BLP was applied to in vivo and simulated FIDs to back-predict missing points up to AD = 0 ms, enabling quantification within a unified basis set framework. ResultsIn vivo and simulated data showed clear AD-dependent variations for several metabolites (Gln, tCho, tNAA, Ins, Tau), with discrepancies frequently >10% despite AD-specific basis sets. Simulations confirmed metabolite-specific biases increasing with AD. BLP reconstruction preserved quantification consistency up to [~]0.98 ms of recovered FIDs, reducing inter-AD mismatches in vivo--particularly for Tau, tNAA and tCho--lowering the mean discrepancy from 10.5% to [~]5%. DiscussionThese findings show that AD affects {superscript 1}H-FID-MRSI quantification in LCModel, whereas BLP reconstruction can harmonize spectra across delays by enabling a virtual AD = 0 ms quantification scheme. This supports BLP as a practical strategy to improve consistency and comparability in MRSI studies.

neuroscience↗

bioRxiv2021

Creatine transporter deficient rat show motor dysfunction linked with cerebellar alterations and muscle creatine deficiency without muscle atrophy

Creatine (Cr) is a nitrogenous organic acid and plays roles as fast phosphate energy buffer to replenish ATP, osmolyte, antioxidant, neuromodulator, and as a compound with anabolic and ergogenic properties in muscle. Cr is taken from the diet or endogenously synthetized by the enzymes AGAT and GAMT, and specifically taken up by the transporter SLC6A8. Loss-of-function mutations in the genes encoding for the enzymes or the transporter cause Cerebral Creatine Deficiency Syndromes (CCDS). CCDS are characterized by brain Cr deficiency, intellectual disability with severe speech delay, behavioral troubles, epilepsy and motor dysfunction. Among CCDS, the X-linked Cr transporter deficiency (CTD) is the most prevalent with no efficient treatment so far. Different animal models of CTD show reduced brain Cr levels, cognitive deficiencies and together they cover other traits similar to those of patients. However, motor function was poorly explored in CTD models and some controversies in the phenotype exist in comparison with CTD patients. Our recently described Slc6a8Y389C knock-in (KI) rat model of CTD showed mild impaired motor function, morphological alterations in cerebellum, reduced muscular mass, Cr deficiency and increased guanidinoacetate content in muscle, although no consistent signs of muscle atrophy. Our results indicate that such motor dysfunction co-occurred with both nervous and muscle dysfunction, suggesting that muscle strength and performance as well as neuronal connectivity might be affected by this Cr deficiency in muscle and brain.

pathology↗

bioRxiv2021

Metabolic and transcriptomic profiles of glioblastoma invasion revealed by comparisons between patients and corresponding orthotopic xenografts in mice

The invasive behavior of glioblastoma, the most aggressive primary brain tumor, is considered highly relevant for tumor recurrence. However, the invasion zone is difficult to visualize by Magnetic Resonance Imaging (MRI) and is protected by the blood brain barrier, posing a particular challenge for treatment. We report biological features of invasive growth accompanying tumor progression and invasion based on associated metabolic and transcriptomic changes observed in patient derived orthotopic xenografts (PDOX) in the mouse and the corresponding patients tumors. The evolution of metabolic changes, followed in vivo longitudinally by 1H-Magnetic Resonance Spectroscopy (MRS) at ultra-high field, reflected growth and the invasive properties of the human glioblastoma transplanted into the brains of mice (PDOX). Comparison of MRS derived metabolite signatures, reflecting temporal changes of tumor development and invasion in PDOX, revealed high similarity to spatial metabolite signatures of combined multi-voxel MRS analyses sampled across different areas of the patients tumors. Pathway analyses of the transcriptome associated with the metabolite profiles of the PDOX, identified molecular signatures of invasion, comprising extracellular matrix degradation and reorganization, growth factor binding, and vascular remodeling. Specific analysis of expression signatures from the invaded mouse brain, revealed extent of invasion dependent induction of immune response, recapitulating respective signatures observed in glioblastoma. Integrating metabolic profiles and gene expression of highly invasive PDOX provided insights into progression and invasion associated mechanisms of extracellular matrix remodeling that is essential for cell-cell communication and regulation of cellular processes. Structural changes and biochemical properties of the extracellular matrix are of importance for the biological behavior of tumors and may be druggable. Ultra-high field MRS reveals to be suitable for in vivo monitoring of progression in the non-enhancing infiltration zone of glioblastoma.

cancer biology↗

bioRxiv2020

A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism

Creatine is an organic compound used as fast phosphate energy buffer to recycle ATP, important in tissues with high energy demand such as muscle or brain. Creatine is taken from the diet or endogenously synthetized by the enzymes AGAT and GAMT, and specifically taken up by the transporter SLC6A8. Deficit in the endogenous synthesis or in the transport leads to Cerebral Creatine Deficiency Syndromes (CCDS). CCDS are characterized by brain creatine deficiency, intellectual disability with severe speech delay, behavioral troubles such as attention deficits and/or autistic features, and epilepsy. Among CCDS, the X-linked creatine transporter deficiency (CTD) is the most prevalent with no efficient treatment so far. Different mouse models of CTD were generated by doing long deletions in the Slc6a8 gene showing reduced brain creatine and cognitive deficiencies or impaired motor function. We present a new knock-in (KI) rat model of CTD holding an identical point mutation found in patients with reported lack of transporter activity. KI males showed brain creatine deficiency, increased urinary creatine/creatinine ratio, cognitive deficiency and autistic features. Slc6a8xY389C KI rat fairly enriches the spectrum of CTD models and provides new data about the pathology, being the first animal model of CTD carrying a point mutation.

pathology↗