Keywords: Probes & Targets, Tumor, Integrated diagnosis and treatment

Motivation: MnO2 combined with MONs offers potential for accurate tumor diagnosis and treatment. Our MMONs, with adjustable hardness, address issues with hard and soft nanoparticles, showing tumor responsivity and enabling MRI. Irisin loading boosts ferroptosis in drug-resistant tumors.

Goal(s): The synthesis of a stiffness-transformable nanoplatform loaded with Irisin achieves magnetic resonance imaging and induces ferroptosis in the tumor microenvironment.

Approach: MMONs and MMONs-Irisin were synthesized, characterized, and their magnetic resonance imaging and cytotoxic effects were validated at both cellular and animal levels.

Results: MMONs-Irisin is deformable, exhibits excellent magnetic resonance imaging effects, and promotes ferroptosis in tumors.

Impact: MMONs are GSH-responsive, with higher T1 and T2 relaxation rates than Magnevist at equal concentrations. They adjust stiffness for enhanced tumor uptake, loaded with Irisin, combat chemotherapy resistance through ferroptosis. MMONs-Irisin holds potential for safe, integrated cancer diagnosis and treatment.

Keywords: Biology, Models, Methods, Elastography, Preclinical, Steatohepatitis, Murine model, Viscoelasticity, Water diffusion, Fat content

Motivation: The relationship between the microstructural changes and the imaging-based biophysical properties of the liver as NASH progresses are not fully established.

Goal(s): We aim to identify quantitative imaging markers that can provide valuable insights into the microstructural progression of NASH.

Approach: We established non-alcoholic steatohepatitis in mice with a defined amino-acid high-fat diet. We performed MRI, MR elastography and histological scoring with automated fat segmentation at different times during the course of NASH.

Results: Our results shed light on liver viscosity and water diffusivity as potential quantitative markers of steatohepatitis progression in mice.

Impact: This study highlights the role of multiparametric-MRI, MR elastography and histopathology to reveal the dynamics of microstructural changes of non-alcoholic steatohepatitis in a mouse model using a clinical scanner. We identify liver viscosity and water diffusivity as reliable quantitative markers.

Keywords: Small Animals, Preclinical

Motivation: Myocarditis causes adverse ventricular remodeling. However, its early diagnosis and intervention measures remain to be explored.

Goal(s): Exploring quantitative CMR for monitoring myocarditis developments.

Approach: Cardiac T1, T2 and ECV mapping were performed in mice at two timepoints. Then the CMR parameters were compared between the control and myocarditis groups. The CMR results were validated against histology.

Results: Early acute phase of myocarditis was characterized by increased T2 and ECV. As time progressed, T2 was reduced to the normal level, while myocarditis native T1 and ECV were much higher than the control. The CMR findings agreed with histology.

Impact: Quantitative CMR parameters may serve as reliable indicators for edema, inflammation and fibrosis that are associated with the progression of myocarditis, and can be used for early diagnosis, monitoring and management of myocarditis.

Keywords: Small Animals, Cardiovascular, T1 mapping

Motivation: Preclinical cardiac T1 mapping in high field encountered a great challenge, such as rapid heart rate, B0 and B1 inhomogeneity, which affects both accuracy and precision in T1. 

Goal(s): We aim to develop an accurate, fast and reproducible T1 mapping method at 9.4 T MRI.

Approach: We adapted inversion efficiency (IE) to the segmented Look-locker sequence and validated it in a phantom, as well as in aorta banding rats.

Results: Segmented Look-Locker T1 mapping with IE is a fast and accurate T1 mapping method, which corrects the imperfection of inversion pulse in high field.

Impact: We have developed a rapid, highly precise T1 mapping technique for rat hearts using 9.4 T MRI, enabling longitudinal scans and comparisons between different animals.

Keywords: Biology, Models, Methods, Ischemia, Contrast Mechanisms, Molecular Imaging

Motivation: Studies on cardiac ischemia reperfusion injury mainly focus on events following an ischemic event.  Our focus were the initial moments during occlusion and reperfusion in a novel murine model.

Goal(s): Our goal was to characterize the dynamic processes occurring during and immediately after ischemia.

Approach: Manganese is a calcium analogue and potent T1-contrast agent for MRI that enters cardiomyocytes through active calcium channels. By exploiting this mechanism, the disruption of calcium homeostasis was monitored during and after ischemia.

Results: Studying the early phase of ischemia is feasible and data suggest a link between the final scar extent and severity of Ca²⁺ homeostasis disruption.

Impact: Preclinical ischemia-reperfusion injury studies can now be complemented with an early marker for subsequent injury. Revealing the dynamic processes occurring during and immediately after an ischemic event might help to assess the effects of applied therapeutics at an earlier stage. 

Keywords: Biology, Models, Methods, Spectroscopy, sodium, rheology, red blood cells

Motivation: Increased blood viscosity has been reported in red blood cell senescence and pathologies of decreased perfusion such as chronic kidney disease.

Goal(s):

• Rheological NMR is a powerful, although still underutilized, tool to assess the molecular-mechanical links in flowing media. This study's primary objective was to explore the dynamic alterations in Na+ interaction with glycocalyx of red blood cells exposed to the physiological shear forces experienced within the microvasculature in health and disease.

Approach:   ²³Na multiple quantum filtered (MQF) rheo-NMR in RBCs suspensions at varied haematocrit.

Results:   ²³Na MQF rheo-NMR are efficient to detect Na+ interaction with glycocalyx of red blood cells under deformation

Impact: Potential sodium “rheo-markers” reflective of blood viscosity in health and disease are proposed.

Keywords: Small Animals, Animals, cirrhosis,Cirrhotic cardiomyopathy

Motivation: As an important complication of cirrhosis, early diagnosis of cirrhotic cardiomyopathy (CCM) has a profound impact on  prognosis of patients.

Goal(s): Find in myocardial strain parameters beyond global longitudinal strain (GLS) that are relevant for early diagnosis of CCM.

Approach: The heart and liver were scanned with magnetic resonance  and multiple strain parameters were obtained from cardiac magnetic resonance to evaluate their potential diagnostic value for CCM and correlation with liver lesions. 

Results: Compared with GLS and left ventricular ejection fraction , short-axis peak diastolic radial strain rate (PDRSR-S) has an earlier time to change, better diagnostic performance, and better correlation with liver lesions.

Impact: We discoveries a myocardial strain parameter , short-axis peak diastolic radial strain rate, who showed excellent potential in the early diagnosis of cirrhotic cardiomyopathy. The discovery laid the foundation for future research and clinical applications.

Keywords: Biology, Models, Methods, Elastography, organoids, high resolution

Motivation: MR-Elastography is technology that shows promises for gauging response to therapy.

Goal(s):   It is hence of great interest to make this technology also available for the quantification of tissue organoids/spheroids. This enables the translation of the same imaging biomarkers to the pre-therapeutic regime.

Approach:  We present a system that allows for contactless quantification of organoid biomechanics at 35micron resolution and show that gauged spheroids as small as 400mm in diameter are properly quantified in terms of shear wave speed.

Results:  The concept allows to “real-word” organoid testing as they are embedded in a collagen dome with buffer solution around to enable drug exposure.

Impact: Using MRE sequence on patient derived materials to predict cancer cells response to chemotherapy, could be a lifetime saver not only for the patient but also for the clinician decision, by testing in vitro several therapies at the same time.

Keywords: Large Animals, Nonhuman Primates, Animals, CMR, pig

Motivation: Domestic pigs are frequently used as experimental animals for cardiovascular research but are subject to somatic growth.

Goal(s): To investigate the relationship of cardiac functional and volumetric parameters with animal somatic growth. 

Approach: In this retrospective CMR study in 58 female Swiss large white pigs, we correlate functional volumetric and dimensional CMR parameters to animal weight.

Results: : Left ventricular mass, left and right ventricular volumes and stroke volumes correlate with animal weight. Weight-independent parameters were left and right ejection fractions. Our findings match values found in humans.

Impact: We provide a regression analysis of clinical functional, volumetric and dimensional CMR parameters for experimental planning and refinement of animal experiments in pigs and illustrate healthy parameter ranges.

Keywords: Small Animals, Joints, CT, Osteoarthritis, Cartilage, Bone, Multimodal imaging

Motivation: This is a clinically inspired project related to Osteoarthritis which focuses on translational research to specifically enhance murine preclinical models with micro-CT and MRI. 

Goal(s): To optimize MRI methods for monitoring of longitudinal repair of a mouse model of osteochondral injury, to validate joint tissue response and assess intervention impact to the injury site.

Approach: The study design features the micro-CT and MRI imaging of the knee joint in a murine osteochondral injury model. 

Results: The optimized MRI protocol was able to demonstrate differences between groups after longitudinal assessment. This technique is an important translational step allowing the measurement of clinically relevant differences.

Impact: The developed multimodal imaging methodology to monitor tissue repair of mouse knee will extensively enhance the development of novel therapies for cartilage and bone repair, and their translatability into the clinic, whilst reducing the number of animals for preclinical research.

Keywords: Biology, Models, Methods, Bladder, Uro-dynamic MRI

Motivation: Recently developed MRI-Urodynamics methods require rigorous validation. In vitro approaches have been implemented, however lack of tissue-like mechanical properties of the in models limits their applicability. 

Goal(s): Develop and implement an ex-vivo bladder model for validation of MRI-Urodynamics.  

Approach: Porcine bladder was obtained and connected to a syringe pump to conduct MRI experiments during filling and voiding at various flow-rates. Simultaneous pressure measurements were performed during MRI.  

Results: Ex-vivo bladder MRI experiments were successfully conducted. MRI-derived flow-rates agree within 10% when compared to the flow-rates imposed by the syringe pump. Pressure-volume analysis provided means of comparison of bladder performance between filling and voiding. 

Impact: 3D dynamic MRI can assess anatomical changes in the bladder during voiding and filling. Systematic validation of this technique can enhance its clinical use.

Keywords: Small Animals, MSK, muscular dystrophy

Motivation: The frequently-used mdx model of Duchenne muscular dystrophy exhibits wide variation in disease severity, confounding detection of treatment effects.

Goal(s): We sought to design a rapid, noninvasive imaging/analysis pipeline to prescreen animals and balance disease severity across treatment groups.

Approach: Axial MR images and T₂ maps were obtained in the hindlimbs of mdx and wildtype mice. A neural network was trained to speed segmentation. The distribution of muscle T₂ values was analyzed.

Results: Semiautomated segmentation reduced image processing time ~tenfold. Pearson Skew and interdecile range of muscle T₂ distributions were repeatable indicators of muscle disease severity and correlated with Evans Blue dye uptake.

Impact: Use of this rapid, non-invasive, semi-automated MRI/analysis pipeline has the potential to improve the sensitivity of preclinical treatment studies by enabling screening of dystrophic mice prior to study enrollment to increase uniformity of muscle pathology across treatment groups.

Keywords: Preclinical Image Analysis, Quantitative Imaging

Motivation: The clinical value of newly ultrafast multiple overlapping-echo detachment T2 mapping (MOLED-T2 mapping) on common liver tumors has not yet been elucidated.

Goal(s): To test the reliability of MOLED-T2 mapping in common hepatic tumors during clinical applications.

Approach: Total of 23 healthy subjects and 59 patients were enrolled in our study. Free breath MOLED-T2 mapping, breath hold MOLED-T2 mapping and most used breath hold GraSE T2 mapping were compared.

Results: There was no significant difference between free breath and breath hold MOLED-T2 mapping. T2 values obtained from two MOLED sequences were significantly lower than those obtained through fb-GraSE-T2 sequence.

Impact: This work will stand up the foundation for subsequent research about MOLED-T2 mapping on  abdomen quantitative MR imaging.

Keywords: Biology, Models, Methods, Diffusion Tensor Imaging, Cardiovascular

Motivation: Changes in myocardial microstructure that underlie post-myocardial infarction (MI) left ventricular (LV) remodelling may contribute to progressive deterioration in cardiac function and increased risk of adverse clinical events.

Goal(s): To assess post-MI temporal alterations of myocardial microstructure.

Approach: A longitudinal Diffusion Tensor CMR (DT-CMR) pre-clinical study was performed, including healthy, 3 days and 4 months post-MI timepoints, followed by ex-vivo imaging at low and high spatial resolution.

Results: High-resolution ex-vivo DT-CMR suggests preserved helical structure within the infarct core in this swine MI model, with endocardial layers appearing more compressed than mid and epicardial layers.

Impact: Improved understanding of temporal alteration of myocardial microstructure and its dynamics post-MI as seen by in-vivo DT-CMR may facilitate diagnosis and prognostication after MI.

Keywords: Large Animals, Nonhuman Primates, Safety, Swine, thermoregulation, temperature curves

Motivation:
Radiofrequency used during MRI exams heat tissue. The temperature increase is unknown and the thermoregulatory responses still need to be analyzed.

Goal(s): To analyse the temperatures within the thresholds. Are any changes seen. Is the biological simulation replicable in living swine.

Approach: SAR levels in the 2.mode were planned in the swine as an animal model.

Results: The thermoregulatory model (temperature going into a plateau) is only one pattern next to 3 other patterns (linear, parabolic, and sinusoidal). So these will change the  calculations of simulations for temperatures in humans receiving MRI exams.

Impact: Radiofrequency induced temperature changes in MRI exams need to be reevaluated as new thermoregulatory patterns are observed. Increased internal temperatures are subconsciously discerned causing thermoregulation to avoid tissue damage.

Keywords: Probes & Targets, Preclinical

Motivation: Early diagnosis of transplant rejection can help to improve the immune-related management of transplant recipients.

Goal(s): Developing the new methods for early and non-invasive diagnosis of acute cellular rejection to unmet clinical needs.

Approach: Develop a PET/MRI dual-model granzyme B (GzmB)  targeted probe for non-invasively detection of transplant acute cellular rejection.

Results: In preclinical heart graft models of rejection, our PET/MRI dual-model GzmB targeted probe allow noninvasive discrimination of early acute cellular rejection mediated by recipient cytotoxic CD8⁺ T cells.

Impact: In the future, this technology developed a PET/MRI dual-model probe for imaging GzmB produced by cytotoxic CD8⁺ T cells, enabling early non-invasive diagnosis of allograft rejection with high sensitivity and high spatial resolution.