Keywords: Deuterium, Deuterium, FDG-PET

Motivation: The regulation of brain glucose metabolism by GLP1-1R has not been fully verified. 

Goal(s): To explore feasibility of dynamic DMRS in mice brain, and the physiological role of GLP-1R in mouse brain glucose metabolism. 

Approach: we apply DMRS and FDG-PET to quantify dynamic cerebral glucose change, and combine with rs-fMRI to investigate changes in whole-brain functional connectivity. 

Results: GLP-1R KO mice exhibit impaired brain glucose metabolism and central nervous system intolerance to high doses of exogenous glucose.  And the functional brain connectivity in GLP-1R KO mice was significantly lower than that in WT group.

Impact: The decline in functional connectivity may hinder the coordination of work and information transmission between brain regions, thus inhibit normal metabolic regulatory processes. These findings provide a theoretical basis for the treatment strategies of disorders related to brain glucose metabolism

Keywords: Non-Proton, Metabolism, Migraine, 31P Spectroscopy, Preclinical, Central Sensitization, Ultra-high field

Motivation: Migraine is a disorder of neuronal hyperexcitability, but previous work has not been able to capture energetic processes non-invasively during active central sensitization, only after or between migraine attacks. 

Goal(s): This preclinical study evaluates whole brain energetic metabolism and remodeling during a nitroglycerin-induced migraine attack.

Approach: ³¹P spectroscopy using ISIS was used to measure phosphocreatine and ATP levels at baseline and then over a 3-hour period post-NTG administration.

Results: Most notable is the increase in phosphocreatine compared to baseline and controls, as well as an increase in ATP compared to baseline. Both indicate energetic remodeling during central sensitization prior to migraine pain onset.

Impact: Increased phosphocreatine and ATP over the entire brain demonstate significant energetic fluxes during cerebral central sensitization and prior to nociception. This energetic remodeling informs understanding of fundamental migraine pathophysiology and its timing, potentially impacting the administration of potential clinical interventions.

Keywords: Non-Proton, Liver, X-Nuclei, 23Na MRI, Sodium, Ultrahigh Field, 7T, Tissue sodium concentration

Motivation: A scarcity in literature values for the tissue sodium concentration (TSC) in the healthy liver complicates the evaluation of the TSC in the diseased liver.

Goal(s): This study aimed to establish TSC levels in one healthy liver on multiple days to explore potential concentration variations.

Approach: The TSC was assessed using B₁ field corrected and respiratory-sorted quantitative ²³Na MRI.

Results: The TSC values obtained in the healthy liver remained stable over a week and aligned with existing literature values.

Impact: The study's finding of a consistent tissue sodium concentration (TSC) over time in one healthy liver is a valuable insight. It indicates that changes in liver TSC might be accurately linked to diseases, which could improve diagnosis of liver diseases.

Keywords: Deuterium, Deuterium, Spectroscopy, Metabolism

Motivation: Most Deuterium Metabolic Imaging (DMI) studies have employed doubly labelled D₂-glucose, but fully labelled D₇-glucose produces higher deuterium concentrations in the brain, providing higher signal-to-noise-ratio measurements and additional information about metabolism.

Goal(s): We carried out a detailed comparison of 7T DMI measurements in the brain in 15 participants who ingested either D₇-glucose or D₂-glucose.

Approach: 3D ²H CSI data was acquired at 7T at natural abundance and then every 15 minutes for ~65- minutes following ingestion of 0.75 g/kg of labelled glucose.

Results: Larger signals and concentrations were measured following D₇-glucose ingestion, D₇/D₂ signal ratios were explained by differing numbers of labels.

Impact: Deuterium metabolic imaging (DMI) using labelled glucose forms a powerful tool for mapping glucose metabolism. D₇-glucose produces higher deuterium concentrations in the brain, providing a higher signal-to-noise-ratio that would be valuable in studies of metabolism in health and disease.

Keywords: Non-Proton, Non-Proton

Motivation: To improve understanding of sodium and water balance in haemodialysis patients.

Goal(s): To study sodium stores in leg muscle and skin in younger and older healthy individuals, and haemodialysis patients, and to assess sodium and water changes following a single haemodialysis session.  

Approach: Sodium (²³Na) MRI of calf skin and muscle in younger older and haemodialysis(HD) patients. ²³Na MRI, and ¹H mDIXON and T₂ relaxometry to study sodium and water content to haemodialysis.

Results: Haemodialysis led to a significant reduction in muscle sodium whilst skin sodium showed little detectable change, ¹H muscle T₂ values showed a significant reduction. 

Impact: Sodium (²³Na) MRI of muscle allows the study of sodium storage with age and in dialysis patients. ²³Na and proton (¹H) T₂ mapping enable the assessment of changes in sodium storage and fluid status in haemodialysis patients.

Keywords: Non-Proton, Non-Proton, Brain Tumours, Sodium Imaging, Multiple Quantum Filteres, Compressed Sensing

Motivation: Leverage cutting-edge enhanced simultaneous single and triple quantum filtered sodium imaging sodium imaging (eSISTINA) at 7T for unparalleled image precision, enhancing diagnostic efficacy and pushing the clinical frontier in brain tumour analysis.

Goal(s): Optimise imaging and relaxometry performance of the eSISTINA sequence without compromising clinically applicability due to exessive measurement times.

Approach: FLORET spiral trajectories coupled with pseudo-randomised undersampling and compressed sensing reconstruction yield significantly enhanced image quality and relaxometry performance of eSISTINA.

Results: Compressed sensing reconstructed images of a brain tumour patient highlight substantial improvements in quality and aquicistion efficiency of eSISTINA at 7T, surpassing prior work at lower field strengths.

Impact: This study demonstrates clearly that eSISTINA at ultra-high field strength is a promising diagnostic tool, offering invaluable insights for clinicians and researchers. Future patient cohort studies will undoubtedly reveal novel perspectives on brain tumours and metabolism.

Keywords: Deuterium, Deuterium, Dynamic 2D fitting; Deuterium metabolic imaging; Brain; 7T

Motivation: Dynamic deuterium metabolic imaging (DMI) data are currently evaluated by first fitting the spectral and then the temporal domain (1D), leading to great fit uncertainty. This might be improved by fitting both domains simultaneously (2D).

Goal(s): To compare dynamic 2D-fitting of time-resolved 3D-DMI data of the human brain and compare its performance to conventional 1D-fitting.

Approach: Simulated and in vivo DMI data were fitted using 1D- and 2D-fitting algorithms and results were compared in terms of precision and accuracy.

Results: 2D-fitting yielded higher precision and accuracy than 1D-fitting for simulated DMI data. For in vivo data, both fitting approaches yielded similar results.

Impact: Improving fitting accuracy to estimate the underlying metabolic kinetics from dynamic deuterium metabolic imaging (DMI) data is crucial, while establishing DMI towards clinical application. 2D-fitting approaches (simultaneous spectral and temporal fitting) could potentially improve overall robustness of the methodology.

Keywords: Deuterium, Cancer, Preclinical

Motivation: Diffuse midline gliomas (DMGs) are devastating pediatric brain tumors. Although MRI is the mainstay for DMG imaging, it does not reliably report on response to therapy.

Goal(s): The goal of this study was to assess the utility of deuterium metabolic imaging for DMGs.

Approach: To this end, we interrogated [6,6’-²H]-glucose metabolism in patient-derived and syngeneic models.

Results: [6,6’-²H]-glucose enables non-invasive visualization of the metabolically active tumor lesion in mice bearing intracranial DMGs. Importantly, [6,6’-²H]-glucose provides an early readout of response to targeted therapy in vivo. Collectively, our studies highlight the potential of [6,6’-²H]-glucose for imaging tumor burden and response to therapy in DMGs.  

Impact: Diffuse midline gliomas are deadly childhood brain tumors. Using clinically relevant patient-derived and murine tumor models, we show that deuterium metabolic imaging using [6,6’-2H]-glucose enables non-invasive assessment of tumor burden and early response to therapy in diffuse midline gliomas.

Keywords: Deuterium, Metabolism

Motivation: Deuterium metabolic imaging (DMI) might permit mapping of cardiac metabolism by MRI.

Goal(s): To port DMI tools developed at 11.7T for mice to 3T, and develop methods for cardiac DMI.

Approach: Simulations, phantoms, and in vivo studies were conducted to measure SNR at 3T, develop an optimized protocol, and account for B0 inhomogeneity.

Results: At 11.7T, cardiac DMI was tested in a control mouse. At 3T, phantom studies showed that multi-echo bSSFP methods yield increased SNR vs. GRE.  B0-mapping helps in isolating the metabolites in phantoms. 

Impact: Development of DMI tools for use in cardiac DMI at clinical field strengths.

Keywords: Deuterium, Deuterium, Alzheimer's Disase

Motivation: Impaired brain energy metabolism at early stage is found to be the driving factor of Alzheimer’s Disease (AD) progression.

Goal(s): The study aim to investigate the potential of using deuterium magnetic resonance imaging to characterize the glucose metabolism in AD mouse model.

Approach: Deuterium magnetic resonance spectroscopic imaging with the administration of [2,3,4,6,6’-²H₅]-D-Glucose in 5xFAD and C57 mice.

Results: Our preliminary results indicate higher glutamine/glutamate (Glx) production rate in 5xFAD mice compared to normal mice, especially in the hypothalamus region. 

Impact: Our work may shed light on developing new method in the early detection of AD based on the glucose metabolism abnormality.

Keywords: Non-Proton, Metabolism

Motivation: Brain sodium (²³Na) MRI can provide sodium concentration information in vivo, but there are still some challenges, such as low SNR and relatively low resolution.

Goal(s): To assess the reproducibility of total sodium concentration (TSC) evaluation  in the putamen and substantia nigra of healthy individuals using 3D ²³Na MRI.

Approach: Ten healthy subjects were scanned twice consecutively using the 3D TFE UTE and T1W sequence to quantify the TCS in the putamen and substantia nigra. The reproducibility was evaluated.

Results: Concentration of sodium in phantoms can be accurately quantified and TSC in putamen, substantia nigra had good consistency for ²³Na MRI.

Impact: ²³Na-MRI shows potential in becoming a stable and useful biomarker for the diagnosis of patients with neurodegenerative diseases.

Keywords: Deuterium, Deuterium

Motivation: The inherently low SNR of DMI hinders clinical viability at 3T.  

Goal(s): We evaluate an anatomically guided reconstruction (AGR) approach to enhance the spatial resolution of DMI scans via exploiting correlated anatomic information in corresponding ¹H images.

Approach: We used segmented MRI scans of patients with CNS tumors to simulate DMI metabolic maps and corresponding ground truth, which were then used to evaluate AGR performance with respect to both SNR and the targeted spatial resolution.  

Results: Findings demonstrated that this AGR approach is largely robust to noise and most successful at upsampling factors between 2-4, after which the reconstructions starts to fail.

Impact: DMI can uncover novel metabolic information about CNS lesions. We demonstrate that mutual anatomic information from ¹H MRI can bring 3T DMI closer to clinically-viable spatial resolutions. Further work is needed to assess its utility across lesion sizes and pathologies.

Keywords: Deuterium, Deuterium, Preclinical

Motivation: Effective treatment response seen in paediatric-type diffuse high grade glioma with conventional MRI can take months to manifest.

Goal(s): Evaluation of ²H-MRS for monitoring the metabolism of deuterated glucose in PDHGG cells and assessing early metabolic response to PI3K inhibition.

Approach: PIK3R1 mutant neurospheres were treated with a dual PI3K/mTOR inhibitor for 72 and 24 hours, and ²H spectra dynamically acquired in the presence of [6,6-²H₂]-glucose.

Results: Treatment significantly reduced glycolytic rates at both timepoints. At 24 hours there was no difference in cell number or viability, highlighting the potential of ²H-MRS to provide an early biomarker of response.

Impact: Establishing acute treatment-induced changes in the glycolytic rate of PDHGG neurospheres using 2H-MRS provides confidence in the sensitivity of deuterium metabolic imaging for assessing the early response of orthotopic PDHGG models to PI3K inhibition in vivo.

Keywords: Deuterium, Deuterium

Motivation: Glioma tumor cells have abnormally higher uptake of methionine, compared to normal brain tissues.

Goal(s): To characterize the methionine preference of glioma cells through deuterium magnetic resonance spectroscopy.

Approach: Deuterium magnetic resonance spectroscopy in glioma C6 and CTX-TNA2 glial cells incubated by [1-²H₃]-methionine

Results: Abnormal uptake of deuterated methionine in glioma cells was revealed by using magnetic resonance deuterium spectroscopy, compared to normal cells

Impact: Deuterium magnetic resonance imaging with deuterium labeled methionine may have the potential in accurate diagnosis and treatment assessment of glioma.

Keywords: Non-Proton, Preclinical, Gelatin scaffolds, 19F MRI/MRS

Motivation: Gelatin-based scaffolds may be seeded by cells or may serve as depots for drugs and ensure their slow release.

Goal(s): The goal of the study was to prepare scaffolds with tunable properties and monitor their stability in time in a mouse model in vivo.

Approach: The scaffolds implanted to mice were monitored by ¹H/¹⁹F MRI, fluorine content was quantified by ¹⁹F MR spectroscopy.

Results: The scaffolds can be easily monitored by ¹⁹F MRI/MRS. The study confirmed that the design of the scaffolds can be fine-tuned for future applications, biodegradation rates may be set from several weeks up to one year.

Impact: Gelatin-based scaffolds pave the road towards qualitatively different drug applications and regenerative medicine. The study evaluated their applicability, traceability by ¹H/¹⁹FMRI, and stability in vivo. Future work should investigate release speed of different compounds (drugs) both hydrophilic and hydrophobic.

Keywords: Deuterium, Deuterium, Relaxation Times, Brain, 7T, Deuterium Metabolic Imaging

Motivation: Deuterium metabolic imaging (DMI) is an emerging Magnetic Resonance technique to non-invasively map the cellular glucose uptake and downstream metabolism. For a reliable concentration estimation, tissue-specific relaxation times are essential, yet only unlocalized relaxation time constants of deuterium labeled resonances are reported. 

Goal(s): Measure tissue-specific relaxation times of deuterated resonances (glucose, glutamate+glutamine).

Approach: Inversion recovery and Hahn spin-echo acquisition schemes were implemented into 3D FID ²H-MRSI using concentric ring trajectory readout.

Results: Measured T₁ and T₂ relaxation time constants of Glc (T₁^GM=56±14ms; T₁^WM=60±19ms; T₂^GM=37±1ms; T₂^WM=36±2ms) and Glx (T₁^WM=167±22ms; T₁^GM=173±12ms; T₂^GM=36±1ms; T₂^WM=34±1ms) were not significantly different between GM and WM.

Impact: Many severe brain pathologies feature regional differences in brain glucose metabolism, therefore tissue-specific (grey and white matter) relaxation times (T₁ and T₂) of deuterium labeled resonances are needed for accurate concentration estimation of the kinetics of energy metabolites (Glc,Glx).