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Lanz, B.

Publications and source records attributed to Lanz, B..

6 recordsLinked to original sources

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↗

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↗

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↗

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↗

Differentiating unirradiated mice from those exposed to conventional or FLASH radiotherapy using MRI

Background and purposeThe FLASH effect expands the therapeutic ratio of tumor control to normal tissue toxicity observed after delivery of ultra-high (>100 Gy/s FLASH-RT) vs. conventional dose rate radiation (CONV-RT). In this first exploratory study, we assessed whether ex-vivo Magnetic Resonance Imaging (MRI) could reveal long-term differences after FLASH-RT and CONV-RT whole-brain irradiation. Materials and methodsFemale C57BL/6 mice were divided into three groups: control (non-irradiated), conventional (CONV-RT 0.1 Gy/s), and ultra-high dose rates (FLASH-RT 1 pulse, 5.5 x 106 Gy/s), and received 10 Gy of whole-brain irradiation in a single fraction at 10 weeks of age. Mice were evaluated by Novel Object Recognition cognitive testing at 10 months post-irradiation and were sampled at 13 months post-irradiation. Ex-vivo brains were imaged with a 14.1 Tesla/26 cm magnet with a multimodal MRI protocol, including T2-weighted TurboRare (T2W) and diffusion-weighted imaging (DWI) sequences. ResultsIn accordance with previous results, cognitive tests indicated that animals receiving CONV-RT exhibited a decline in cognitive function, while FLASH-RT performed similarly to the controls. MRI showed decreased hippocampal mean intensity in the CONV-RT mice compared to controls but not in the FLASH-RT group. Comparing CONV-RT to control, we found significant changes in multiple whole-brain diffusion metrics, including the mean Apparent Diffusion Coefficient (ADC) and Mean Apparent Propagator (MAP) metrics. By contrast, no significant diffusion changes were found between the FLASH-RT and control groups. In an exploratory analysis compared to controls, regional diffusion metrics were primarily altered in the basal forebrain and the insular cortex after CONV-RT, and after FLASH-RT, a trend reduction was also observed. ConclusionThis study presents initial evidence that MRI can uncover clear changes in the brain after CONV-RT but not after FLASH-RT. The MRI results aligned with the observed cognitive protection after FLASH-RT, indicating the potential use of MRI to analyze the FLASH response.

neuroscience↗

Deletion of Crtc1 leads to hippocampal neuroenergetic impairments associated with depressive-like behavior

Mood disorders (MD) are a major burden on society as their biology remains poorly understood, challenging both diagnosis and therapy. Among many observed biological dysfunctions, homeostatic dysregulation, such as metabolic syndrome (MeS), shows considerable comorbidity with MD. Recently, CREB-regulated transcription coactivator 1 (CRTC1), a regulator of brain metabolism, was proposed as a promising factor to understand this relationship. Searching for imaging biomarkers and associating them with pathophysiological mechanisms using preclinical models, can provide significant insight into these complex psychiatric diseases and help the development of personalized healthcare. Here, we used neuroimaging technologies to show that deletion of Crtc1 in mice leads to an imaging fingerprint of hippocampal metabolic impairment related to depressive-like behavior. By identifying the underlying molecular/physiological origin, we could assign an energy-boosting mood-stabilizing treatment, ebselen, which rescued behavior and neuroimaging markers. Finally, our results point towards the GABAergic system as a potential therapeutic target for behavioral dysfunctions related to metabolic disorders. This study provides new insights on Crtc1s and MeSs relationship to MD and establishes depression-related markers with clinical potential.

neuroscience↗