Impact of truncating diffusion MRI scans on diffusional kurtosis imaging.

OBJECTIVE: Diffusional kurtosis imaging (DKI) extends diffusion tensor imaging (DTI), characterizing non-Gaussian diffusion effects but requires longer acquisition times. To ensure the robustness of DKI parameters, data acquisition ordering should be optimized allowing for scan interruptions or shortening. Three methodologies were used to examine how reduced diffusion MRI scans impact DKI histogram-metrics: 1) the electrostatic repulsion model (OptEEM); 2) spherical codes (OptSC); 3) random (RandomTRUNC). MATERIALS AND METHODS: Pre-acquired diffusion multi-shell data from 14 female healthy volunteers (29±5 years) were used to generate reordered data. For each strategy, subsets containing different amounts of the full dataset were generated. The subsampling effects were assessed on histogram-based DKI metrics from tract-based spatial statistics (TBSS) skeletonized maps. To evaluate each subsampling method on simulated data at different SNRs and the influence of subsampling on in vivo data, we used a 3-way and 2-way repeated measures ANOVA, respectively. RESULTS: Simulations showed that subsampling had different effects depending on DKI parameter, with fractional anisotropy the most stable (up to 5% error) and radial kurtosis the least stable (up to 26% error). RandomTRUNC performed the worst while the others showed comparable results. Furthermore, the impact of subsampling varied across distinct histogram characteristics, the peak value the least affected (OptEEM: up to 5% error; OptSC: up to 7% error) and peak height (OptEEM: up to 8% error; OptSC: up to 11% error) the most affected. CONCLUSION: The impact of truncation depends on specific histogram-based DKI metrics. The use of a strategy for optimizing the acquisition order is advisable to improve DKI robustness to exam interruptions.

Glucose fluxes in glycolytic and oxidative pathways detected in vivo by deuterium magnetic resonance spectroscopy reflect proliferation in mouse glioblastoma.

OBJECTIVES: Glioblastoma multiforme (GBM), the most aggressive glial brain tumors, can metabolize glucose through glycolysis and mitochondrial oxidation pathways. While specific dependencies on those pathways are increasingly associated with treatment response, detecting such GBM subtypes in vivo remains elusive. Here, we develop a dynamic glucose-enhanced deuterium spectroscopy (DGE 2H-MRS) approach for differentially assessing glucose turnover rates through glycolysis and mitochondrial oxidation in mouse GBM and explore their association with histologic features of the tumor and its microenvironment. MATERIALS AND METHODS: GL261 and CT2A glioma allografts were induced in immunocompetent mice and scanned in vivo at 9.4 Tesla, harnessing DGE 2H-MRS with volume selection and Marchenko-Pastur PCA (MP-PCA) denoising to achieve high temporal resolution. Each tumor was also classified by histopathologic analysis and assessed for cell proliferation (Ki67 immunostaining), while the respective cell lines underwent in situ extracellular flux analysis to assess mitochondrial function. RESULTS: MP-PCA denoising of in vivo DGE 2H-MRS data significantly improved the time-course detection (~2-fold increased Signal-to-Noise Ratio) and fitting precision (-19 ± 1 % Cramér-Rao Lower Bounds) of 2H-labelled glucose, and glucose-derived glutamate-glutamine (Glx) and lactate pools in GL261 and CT2A orthotopic tumors. Kinetic modeling further indicated inter-tumor heterogeneity of glucose consumption rate for glycolysis and oxidation during a defined epoch of active proliferation in both cohorts (19 ± 1 days post-induction), with consistent volumes (38.3 ± 3.4 mm3) and perfusion properties prior to marked necrosis. Histopathologic analysis of these tumors revealed clear differences in tumor heterogeneity between the two GBM models, aligned with metabolic differences of the respective cell lines monitored in situ. Importantly, glucose oxidation (i.e. Glx synthesis and elimination rates: 0.40 ± 0.08 and 0.12 ± 0.03 mM min-1, respectively) strongly correlated with cell proliferation across the pooled cohorts (R = 0.82, p = 0.001; and R = 0.80, p = 0.002, respectively), regardless of tumor morphologic features or in situ metabolic characteristics of each GBM model. CONCLUSIONS: Our fast DGE 2H-MRS enables the quantification of glucose consumption rates through glycolysis and mitochondrial oxidation in mouse GBM, which is relevant for assessing their modulation in vivo according to tumor microenvironment features such as cell proliferation. This novel application augurs well for non-invasive metabolic characterization of glioma or other cancers with mitochondrial oxidation dependencies.

Toward more robust and reproducible diffusion kurtosis imaging.

PURPOSE: The general utility of diffusion kurtosis imaging (DKI) is challenged by its poor robustness to imaging artifacts and thermal noise that often lead to implausible kurtosis values. THEORY AND METHODS: A robust scalar kurtosis index can be estimated from powder-averaged diffusion-weighted data. We introduce a novel DKI estimator that uses this scalar kurtosis index as a proxy for the mean kurtosis to regularize the fit. RESULTS: The regularized DKI estimator improves the robustness and reproducibility of the kurtosis metrics and results in parameter maps with enhanced quality and contrast. CONCLUSION: Our novel DKI estimator promotes the wider use of DKI in clinical research and potentially diagnostics by improving the reproducibility and precision of DKI fitting and, as such, enabling enhanced visual, quantitative, and statistical analyses of DKI parameters.

Double diffusion encoding and applications for biomedical imaging.

Diffusion Magnetic Resonance Imaging (dMRI) is one of the most important contemporary non-invasive modalities for probing tissue structure at the microscopic scale. The majority of dMRI techniques employ standard single diffusion encoding (SDE) measurements, covering different sequence parameter ranges depending on the complexity of the method. Although many signal representations and biophysical models have been proposed for SDE data, they are intrinsically limited by a lack of specificity. Advanced dMRI methods have been proposed to provide additional microstructural information beyond what can be inferred from SDE. These enhanced contrasts can play important roles in characterizing biological tissues, for instance upon diseases (e.g. neurodegenerative, cancer, stroke), aging, learning, and development. In this review we focus on double diffusion encoding (DDE), which stands out among other advanced acquisitions for its versatility, ability to probe more specific diffusion correlations, and feasibility for preclinical and clinical applications. Various DDE methodologies have been employed to probe compartment sizes (Section 3), decouple the effects of microscopic diffusion anisotropy from orientation dispersion (Section 4), probe displacement correlations, study exchange, or suppress fast diffusing compartments (Section 6). DDE measurements can also be used to improve the robustness of biophysical models (Section 5) and study intra-cellular diffusion via magnetic resonance spectroscopy of metabolites (Section 7). This review discusses all these topics as well as important practical aspects related to the implementation and contrast in preclinical and clinical settings (Section 9) and aims to provide the readers a guide for deciding on the right DDE acquisition for their specific application.

Sustainable computational science: the ReScience initiative.

Computer science offers a large set of tools for prototyping, writing, running, testing, validating, sharing and reproducing results; however, computational science lags behind. In the best case, authors may provide their source code as a compressed archive and they may feel confident their research is reproducible. But this is not exactly true. James Buckheit and David Donoho proposed more than two decades ago that an article about computational results is advertising, not scholarship. The actual scholarship is the full software environment, code, and data that produced the result. This implies new workflows, in particular in peer-reviews. Existing journals have been slow to adapt: source codes are rarely requested and are hardly ever actually executed to check that they produce the results advertised in the article. ReScience is a peer-reviewed journal that targets computational research and encourages the explicit replication of already published research, promoting new and open-source implementations in order to ensure that the original research can be replicated from its description. To achieve this goal, the whole publishing chain is radically different from other traditional scientific journals. ReScience resides on GitHub where each new implementation of a computational study is made available together with comments, explanations, and software tests.