Keywords: Oxygenation, Oxygenation

Motivation: Non-invasive measurement of cerebral venous oxygenation (Y_v) is of critical importance in numerous brain diseases. 

Goal(s): The present work proposed a fast method to quantify regional Y_v map for both large and small veins, named T₂-Relaxation-Under-Velocity-Encoding-and-Rapid Acquisition (TRU-VERA). 

Approach: It isolates blood spins from static tissue with velocity-encoding preparation, modulates the T₂ weighting of venous signal with T₂-preparation and utilizes a bSSFP readout to achieve fast acquisition with high resolution.

Results: Venous T₂ measured with TRU-VERA was highly correlated with T₂ from TRUST and showed an excellent test-retest reproducibility with a CoV of 1.2% for large veins and 3.6% for small veins.

Impact: The proposed TRU-VERA sequence is a promising method to for non-contrast and fast assessment of vessel-specific oxygenation, thus regional cerebral oxygen metabolism, in a number of diseases. 

Keywords: Oxygenation, Oxygenation

Motivation: How does single bout of exercise affect brain oxygen metabolism and BBB permeability in addition to perfusion remains unclear. 

Goal(s): This study aims to dynamically monitor the acute changes in cerebral physiology subsequent to a singular aerobic exercise training session

Approach: Multiple indices were quantified, including CBF as gauged by PC MRI, Y_v and CMRO₂ as assessed by TRUST MRI, BBB E and PS as determined via WEPCAST MRI.

Results: We found a significant increase in participants' CBF and CMRO₂ post-exercise, post-exercise stability in E and a significant increase in PS were also observed.

Impact: Our findings suggest that a singular bout of moderate-intensity aerobic exercise can induce acute alterations in cerebral hemodynamics, metabolic processes, and blood-brain barrier permeability.These findings may shed light on the initial stages of the clinical implications of aerobic exercise.

Keywords: Oxygenation, Neuro, quantitative BOLD

Motivation: Standard low-resolution 2D-GRE acquisition for T₂* mapping in mqBOLD MRI may suffer from long scan durations and insufficient quantification accuracy.

Goal(s): Improving quantification accuracy by switching from 2D to high-resolution 3D multi-echo GRE while simultaneously reducing scan duration by applying compressed sensing (CS) acceleration with deep-learning-based reconstruction.

Approach: T₂* maps from low-resolution 2D-GRE and high-resolution 3D-GRE with different acceleration factors were compared in 11 healthy volunteers based on visual inspection and VOI-analyses.

Results: 3D-GRE yields high-resolution parameter maps with improved T₂* values for GM/WM in less than half the scan duration compared to standard 2D-GRE when using CS acceleration with DL-based reconstruction.

Impact: High-resolution 3D-GRE with compressed sensing acceleration and deep-learning-based reconstruction was compared to standard 2D-GRE visually and quantitatively. 3D-GRE enables clinically feasible scan durations with improved and reliable T₂* mapping, which may add to the clinical applicability of oxygenation-sensitive mqBOLD MRI.

Keywords: Molecular Imaging, Cell Tracking & Reporter Genes

Motivation: A non-invasive imaging technology for monitoring cell survival and in-vivo migration after transplantation is critical to optimizing and translating stem cell-based therapies.

Goal(s): To extend our previously reported bright-ferritin cell tracking platform to monitoring stem cell therapy, we investigated tracking human neural progenitor cells transplanted in the rat spinal cord. 

Approach: In-vitro assays of proliferation and differentiation, and imaging both in vitro on cell pellets and in vivo in rats were performed.

Results: Monitoring rats on MRI over seven weeks confirmed the ability to assess cell retention and distribution in the rat spinal cord.

Impact: Our bright-ferritin platform demonstrated no adverse effects on human neural progenitor cells. Stem cells injected in the rat spinal cord could be tracked longitudinally and on-demand via a bright T1-contrast on MRI.

Keywords: Molecular Imaging, Molecular Imaging

Motivation: Simultaneous enhancing MRI signals and effectively generating and activating immune cells is a significant challenge when using one contrast agent.

Goal(s): This work aims to develop nanoparticles of guiding tumor synergistic therapy using ¹H/¹⁹F MRI while activating the STING pathway.

Approach: FMBI nanoparticles were designed for enhancement of ¹H/¹⁹F MRI and activation of the immune system.

Results: FMBI nanoparticles responsively release Mn ions in the tumor microenvironment to enhance the signals of ¹H/¹⁹F MRI and improve immune pathway activity and anti-tumor efficacy.

Impact: Our synthesized FMBI nanoparticles are a STING pathway-activatable contrast agent that can be used for ¹H/¹⁹F MRI-guided tumor therapy with high efficacy, which shows promise for effective tumor immunotherapy.

Keywords: Molecular Imaging, Molecular Imaging, anti-thrombus

Motivation: After percutaneous coronary intervention, systemic dual antiplatelet therapy prevents thrombosis which may increase the bleeding risk, especially in populations at high risk of bleeding.

Goal(s): The aim of this study was to develop PLGA-Fe₃O₄-Ticagrelor microspheres (PFTm), for local infusing to injured artery wall for preventing thrombosis.

Approach: Firstly, the abdominal aorta of rabbits was injured by balloon, and PLGA-Fe3O4-Ticagrelor microspheres were infuded into the injured artery, and T2WI imaging was performed.

Results: PFTm was successfully developed, which can effectively prevent thrombosis.

Impact: This study provides a new concept of local infusion for prevention of thrombosis after PCI.

Keywords: Oxygenation, Oxygenation, qBOLD

Motivation: To investigate sources of error in a new quantitative BOLD technique incorporating an independent measure of deoxygenated blood volume.

Goal(s): Simulate the effect of systematic error and system noise on estimates of oxygen extraction fraction.

Approach: Monte Carlo simulations of the random walk of protons around deoxygenated blood vessels modelled as infinite cylinders were performed using a standard approach.

Results: These simulations show that introducing an independent measure of DBV into the qBOLD framework provides improved estimates of oxygen extraction fraction.

Impact: This improved technique for mapping oxygen extraction has wide applications in the study of neurological disorders including stroke, dementia and cancer.

Keywords: Molecular Imaging, Metabolism, lipid composition; echo-planar spectroscopic imaging

Motivation: Investigating lipid composition in different tissues in vivo is essential. Demand exists for rapid, high-resolution chemical-shift imaging to analyze lipids.

Goal(s): We aimed to employ EPSI to simultaneously target lipid signals and suppress water, enabling precise in-vivo quantification of lipid composition in various tissues for the first time.

Approach: We implemented EPSI incorporating chemical-shift-selective adiabatic-refocusing pulses for lipid refocusing, with a full-automated pipeline for data reconstruction and lipid composition calculation.

Results: Phantom and in-vivo experiments validate the technique's effectiveness. The technique successfully differentiates various vegetable oils and lipid emulsions precisely and quantifies lipid composition with high spatial resolution in mice’s neck and abdomen.

Impact: Lipid-targeted EPSI technology surpasses traditional single-voxel spectroscopy or multi-echo chemical-shift water-fat imaging by providing higher spatial and spectral resolution, empowering researchers with deeper insights into lipid metabolism for future investigations.

Keywords: Molecular Imaging, Molecular Imaging

Motivation: The diagnosis of heart failure is based on clinical symptoms because noninvasive methods for early diagnosis are still insufficient.

Goal(s): Considering reactive oxygen species contribute to heart failure, we hypothesized much earlier signs of heart failure could be captured by focusing on redox metabolism.

Approach: We used a doxorubicin-induced mouse model of heart failure and analyzed at an early stage. To visualize redox metabolism, we used in vivo dynamic nuclear polarization MRI. We also evaluated the cardiomyocytes microscopically. 

Results: The intracardiac redox metabolism was enhanced in 30 min after doxorubicin administration compared to the control group although no significant cardiomyocyte changes were observed.

Impact: In the early stages of heart failure, redox metabolism is altered even before the morphological changes are observed microscopically. These data provide a technique for detecting heart failure earlier and less invasively than conventional testing methods.

Keywords: Molecular Imaging, CEST & MT, Glucosamine, MRI, CEST, Metabolism, Brain

Motivation: Anesthetic drugs vary in their capacity to interfere with homeostatic mechanisms responsible for glucose metabolism in the brain, thus pose a possible constraint in the study design.

Goal(s): To evaluate the preferred anesthesia protocol for preclinical imaging of glucosamine metabolism in healthy mice brains. 

Approach: The effects of different anesthetics procedures on brain glucosamine metabolism were investigated using the CEST MRI method.

Results: Mice injected with glucosamine and anesthetized with 1.5% isoflurane exhibited a low and insignificant increase in MTRasym signals in the cortex, whereas mice given 0.8% isoflurane combined with midazolam demonstrated a significant increase in MTRasym signals in the cortex.

Impact: Combining low levels of isoflurane with midazolam anesthesia, enables increased glucosamine CEST MRI signal, indicating enhanced glucosamine uptake through the BBB. These findings offer valuable insights for optimizing glucosamine metabolic imaging, which can be extended to other glucose analogs.

Keywords: Oxygenation, Oxygenation, Contrast Mechanism

Motivation: Quantitative mapping of oxygen extraction fraction (OEF) is critical to evaluate brain tissue viability and function in neurologic disorders. A recent deep learning-based OEF technique, namely QQ-NET, provided OEF maps sensitive to disease-related abnormalities. However, QQ-NET suffers from training data dependency and requires extensive amount of training data.

Goal(s): Our goal is to resolve the training data dependency issue.

Approach: We developed a novel deep learning scheme, namely QQ-NTD, which minimizes the biophysics model fidelity on each single dataset. 

Results: The proposed QQ-NTD provided a more accurate OEF than QQ-NET.

Impact: With no need for extensive training and independence from input imaging parameters, our novel deep learning approach, QQ-NTD, can be used readily used to obtain OEF maps in clinical setting. 

Keywords: Molecular Imaging, Hyperpolarized MR (Non-Gas), DNP-MRI molecular probe, DPP-4

Motivation: Dipeptidyl peptidase-4 (DPP-4) is a biologically important peptidase known as a biomarker and therapeutic target for type 2 diabetes and cancers. Therefore, detection of DPP-4 activity can be a useful method for early diagnosis and treatment efficacy assessment. 

Goal(s): Development of a DNP-MRI molecular probe for detecting DPP-4 activity in vivo

Approach: We performed molecular designs of DNP-MRI molecular probes for meeting physicochemical properties. For evaluation of enzymatic reactivity of the probes, enzymatic reaction parameters (K_m, k_cat) were measured. The optimized probe was applied for DNP-MRI experiments using mice. 

 

Results: We developed a DNP-MRI molecular probe to detect DPP-4 activity in vivo.

Impact: With design strategy based on recognition mechanism, we have developed a DNP-MRI molecular probe against DPP-4, which has been difficult to develop so far. New probe enables detection of DPP-4 activity in vivo and will be useful for medical applications.

Keywords: Oxygenation, Tumor

Motivation: There is a need for non-invasive imaging markers for tumor oxygenation to develop hypoxia-targeted treatment.

Goal(s): Extend dynamic oxygen-enhanced MRI to incorporate T₁ and T₂* contrast, enhancing our ability to assess tumor tissue oxygenation more effectively.

Approach: Independent Component Analysis maps were used to analyze the signal intensity change in T₁ and T₂* weighted images for pancreatic PDX tumour models in 26 mice, scanned at 7T.

Results: The results showed a significant correlation between ΔT₁ and ΔT₂* in two PDX tumor models, but not in another model. This discrepancy is attributed to differences in tissue oxygenation inherent to the PDX tumor models studied.

Impact: This research demonstrates the potential of dynamic oxygen-enhanced MRI to differentiate tissue oxygenation in pancreatic PDX tumor models. It highlights the complexity of the relationship between T1 and T2* signal changes induced by a cyclic gas breathing challenge.

Keywords: Oxygenation, Metabolism, CMRO2 & oxygen extraction fraction & OEF & calibrated fMRI

Motivation: Gas-calibrated fMRI provides a sensitive measurement of cerebral oxygen consumption, but its applicability is limited to young, healthy participants who can tolerate the gas challenges.

Goal(s): Our goal was to establish the feasibility of breath-hold calibrated fMRI (bhc-fMRI) to replace gas challenges.

Approach: We compared bhc-fMRI to a global oxygen extraction fraction (OEF) measurement, measured within session repeatability and tested the sensitivity of the method to a visual stimulus.

Results: We found similar agreement to global OEF measurements as for gas-calibrated fMRI and moderate within session repeatability. Robust responses to continuous visual stimulation of CBF/CMRO2/OEF (+15%/+11%/-3%) demonstrate good sensitivity of the bhc-fMRI method.

Impact: We establish breath-hold calibrated fMRI as a viable alternative to gas-calibrated fMRI for mapping cerebral oxygen consumption. Breath-hold calibrated fMRI is simple to implement and is tolerable for ageing cohorts and patients with neurodegenerative pathologies.

Keywords: Molecular Imaging, Cancer

Motivation: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive form of cancer with a low survival rate. Immunotherapies have been able to overcome some of the barriers of traditional therapy with PDAC, resulting in increased survival. However, immunotherapy results in responsive and non-responsive tumors.

Goal(s): This study aims to use MR molecular imaging with a contrast agent that's specific to the tumor microenvironment to determine responders and monitor therapy.

Approach: MR molecular imaging T1w images at discrete timepoints with contrast injection and during therapy. 

Results: CNR changes were detected using MR molecular imaging on mice bearing PDAC tumors during a vaccine regimen. 

Impact: There is an absence of biomarkers/predictive tools for pancreatic cancer response to immunotherapy. There’s a critical need for therapeutic strategies that improve patient outcomes in tandem with imaging methods that can monitor disease progression and accurately guide clinical decision making.

Keywords: Molecular Imaging, Cell Tracking & Reporter Genes, Zip14, Manganese-enhanced MRI, Neurons, Mesoscale connectivity

Motivation: Zip14 is an in vivo MRI-visible gene expression reporter system capable of producing focal signal changes without administration of additional contrast agents. However, it is not yet known how much contrast-enhanced MRI will improve sensitivity for Zip14 expression.

Goal(s): Our goal was to understand how systemically delivered manganese (Mn²⁺)-enhanced MRI (MEMRI) would improve Zip14 contrast.

Approach: Zip14 was expressed in the mouse brain and MRI was performed as previously described. MnCl₂ was injected intraperitoneally and MEMRI was performed.

Results: MEMRI improved Zip14 contrast by approximately four-fold at the injection site, by two-fold at sites of anterograde tracing, and revealed previously undetectable tracing sites.

Impact: Although supplemental Mn²⁺ is not required to observe T1-weighted MRI signal enhancement produced by Zip14 expression, it can significantly improve contrast. Increased sensitivity for Zip14 expression with MEMRI will improve measurement of neural connectivity, degeneration, and plasticity in vivo.