Keywords: Contrast Agents, DSC & DCE Perfusion

Motivation: Perfusion studies using DSC-MRI offer insights into vascular aspects of cerebral pathophysiology by allowing us to estimate viable perfusion characteristics. 

Goal(s): Previous studies have shown successful implementation of DSC MRI toolbox to characterise human brain perfusion, but its application to animal data remains unexplored. Our goal is to characterize perfusion parameters in mouse model using DSC-MRI-toolbox.

Approach: We slightly modified and implemented DSC-MRI-toolbox to meaure CBV, CBF and MTT in different regions of mouse brain such as cortex, hippocampus and thalumus.

Results: Initial data analysis shows a successful implementation of the DSC-MRI-toolbox and allowing us to estimate perfusion parameters in preclinical data.

Impact: A successful implementation of DSC-MRI toolbox in mouse models will allow us to estimate perfusion parameters such as CBV, CBF, MTT and CBV with leakage correction, which will be important for characterising tissue viability in stroke and brain injury models.

Keywords: Contrast Agents, Contrast Agent

Motivation: The unique microenvironment of tumors making detection of microenvironmental alterations a valuable asset for early diagnosis of tumors.

Goal(s): This study focuses on exploring impact of Fe3O4 NPs on changes in the tumor microenvironment's acidity.

Approach: By combining them with CEST exogenous contrast agent, we evaluated the feasibility of dual-contrast imaging.

Results: In vitro MRI results suggest that Fe3O4 NPs can act as stable reference agents under varying pH conditions, providing negative contrast for T2-weighted MRI. The CEST effect shows a strong correlation with pH, allowing for quantitative assessment of pH shifts in tumor microenvironment, and can be controlled by adjusting Fe3O4 concentration.

Impact: These preliminary findings represent an initial stride toward dual-contrast imaging involving CEST and T2 contrast agents, with the potential for further expansion in future in vivo investigations.

Keywords: Contrast Agents, Lung, MRI, collagen, Protein-based contrast agent, lung fibrosis, IPF, COPD, lung cancer

Motivation: MRI diagnosis of lung has a limitation due to the air in the lungs which prevents the water signals. We use precision MRI to image the small lesions or fibrosis in the lung.

Goal(s): Our goal is to quantitatively stage the lung diseases by MRI contrast agents.

Approach: Our novel MRI contrast agent is biomarker specific which enables it target to the lung lesions or fibrosis.

Results: We are able to image the lung cancer and metastasis as well as lung fibrosis using our developed MRI contrast agent.

Impact: The imaging of lung tumor lesion or fibrosis is always hindered by the lung features. Our novol contrast agents enable us to image the lung diseases at early stages.

Keywords: Contrast Agents, Contrast Agent, Regional Homogeneity, Functional Connectivity

Motivation: Contrast agents are widely used to increase the contrast difference between normal and abnormal tissues. Existing literature primarily focuses on the structural and perfusion effects of CAs, leaving a knowledge gap regarding their potential functional repercussions. 

Goal(s): We aimed to explore the potential impact of CA administration on brain function. 

Approach: We applied a combination of regional homogeneity, ROI-to-ROI, and seed-to-voxel FC analyses to rs-fMRI data from five participants before and after CA injection.

Results: Our ReHo analysis showed no significant changes of local connectivity pattern, while ROI-to-ROI and seed-to-voxel FC analyses did yield significant FC changes at network level after CA administration.

Impact: Even though the small sample size, our findings may raise an intriguing possibility that CA may indeed have the potential to influence brain function, particularly when examined at a network level. 

Keywords: Contrast Agents, Contrast Agent, pH sensor, temperature sensor, transition metal complex, MRSI, early cancer detection

Motivation: Gadolinium based contrast agents (GBCAs) are reported to be toxic and associated with nephrogenic systemic fibrosis (NSF). Alternative options should be developed to minimize toxicity.

Goal(s): Develop alternative biocompatible transition metal-based MRI agents for advanced imaging.

Approach: Using paramagnetic high spin Fe(II), Co(II), and Ni(II) ions coordinated with well-established cyclic ligands for enhanced MRS imaging to detect cancer tumors at an early stage.

Results: Fe(II)DOTA-4AmC^2-, Co(II)DOTA-4AmC^2-, and Ni(II)DOTA-4AmC^2- were synthesized and characterized. Their in vitro pH and temperature sensing capabilities were assessed using BIRDS at 11.7T.

Impact: These biocompatible pH sensors can be employed for in vivo pH mapping for early cancer diagnosis and can also be adapted for clinical applications.

Keywords: Contrast Agents, Contrast Agent

Motivation: The correlations between signal enhancement by gadolinium (Gd) complexes and pulse sequences or parameters are not well elucidated.

Goal(s): To investigate the influence of repetition time (TR), echo time (TE), inversion time (TI) and flip angle (FA) on signal intensity corresponding to Gd concentration.

Approach: Phantom containing various Gd concentration solutions was scanned using pulse sequences with various TR, TE, TI and FA.

Results: Pulse sequences with longer TR and shorter TE increased signal intensity in lower and higher Gd concentrations, respectively. Application of longer TI and higher FA increased signal intensity at lower and higher Gd concentrations, respectively.

Impact: Pulse sequences with long TR, long TI or low FA can improve SE in human tumor tissue with Gd concentrations less than 2 mM, while high FA is appropriate in high Gd concentration environments such as MR angiography. 

Keywords: Contrast Agents, Cancer, Simultaneous PET/MRI, 68Ga contrast agent, extracellular pH measurement, 4T1

Motivation: The measurement of extracellular pH (pHe) is very important for studying the cancer development, progression, and therapeutic response.

Goal(s): Accurately measure the pHe for 4T1 tumor and 0.2 pH change in vitro independent on the concentration of MRI contrast reagent. 

Approach: To co-inject the synthesized pH sensitive MRI contrast reagent and the PET reagent with the same pharmacokinetic functions and DCE MRI and dynamic PET scan were obtained simultaneously.

Results: The pHe change of the bicarbonate treatment for the acidosis tumor type can be measured by our PET/MRI co-inject reagent. 

Impact: PET/MRI co-inject reagent makes it possible for the pHe measurement independent of the concentration of MRI contrast reagent. 

Keywords: Contrast Agents, Quantitative Imaging

Motivation: Waste clearance mechanisms are essential to maintain homeostasis of the brain. Impairment of such mechanisms may play a key role in various diseases.

Goal(s): To gain insights into waste clearance processes and propose characteristic metrics to describe them.

Approach: We injected contrast agent intravenously and monitored clearance with serial T1 mapping utilizing fast single-shot T1 acquisition with radial FLASH and NLINV reconstruction in healthy volunteers. 

Results: Time-T1 values of full protocol with 35 acquisitions fit well to our exponential model and can be characterized by clearance time $$$\tau$$$ and biggest T1 difference max ΔT1. A dramatically reduced acquisition protocol gives similar results.

Impact: Advanced fast single-shot T1 mapping is promising to characterize waste clearance function in the human brain. Because of a short whole brain acquisition time of 3 minutes it can be integrated easily into existing clinical protocols.

Keywords: Biomarkers, Quantitative Imaging, brain, quantitative MRI, biophysical model

Motivation: Quantitative MRI is attractive for investigating pathological tissue changes, yet translation towards clinical research remains challenging. 

Goal(s): Our goal was to explore sensitivity of a fast quantitative multi-parametric mapping protocol combined with biophysical models at 3T to multiple sclerosis subtypes.

Approach: We combined quantitative maps of magnetization transfer saturation, proton density, longitudinal and transverse relaxation rates with relaxivity approaches to disentangle water and macromolecular tissue driven changes and to identify MRI biomarkers of focal and diffuse demyelination or inflammation.

Results: We found significant alterations in white matter and lesions of surrogates for myelin and iron compared to controls and worsening with disease severity.

Impact: A fast quantitative multi-parameter mapping protocol combined with biophysical models based on in vivo relaxivity approaches in multiple sclerosis at 3T is sensitive to brain tissue alterations in patients, suggesting disease-specific demyelination and inflammation. An association with disability suggests disease-relevance.

Keywords: Contrast Agents, Vessels, Vascular

Motivation: Ferumoxytol is a superparamagnetic iron-oxide agent increasingly used for MR angiography. Cost can potentially be reduced by using a newly introduced generic ferumoxytol, so long as the relaxivity and image quality are similar.

Goal(s): To compare the relaxivity and image quality of brand name ferumoxytol (Feraheme®, AMAG Pharmaceuticals) with generic ferumoxytol (Sandoz), and determine optimal dose and acquisition parameters.

Approach: Phantom experiment and in-vivo dose accumulation with flip angle optimization, using an intra-individual cross-over design.

Results: No clinically relevant differences in relaxivity and MR angiography image quality were observed between ferumoxytol agents. The optimal flip angle and dose are 20° and 5mg/kg, respectively.

Impact: Brand name ferumoxytol (Feraheme®, AMAG Pharmaceuticals) and generic ferumoxytol (Sandoz) are interchangeable for MR angiography. The use of a generic agent may lead to reduction in cost. 

Keywords: Contrast Agents, Contrast Mechanisms, Ferumoxytol

Motivation: Ferumoxytol is becoming more widely used as a contrast agent, yet the optimum dose for use in cardiac MRI remains unknown.

Goal(s): To evaluate whether reducing the contrast dose to 2 or 1mg/kg will affect the image quality and diagnostic accuracy.

Approach: Forty-five patients with complex congenital heart disease had a 3D-IR-SSFP sequence performed at two different ferumoxytol doses. Twenty were in the ferumoxytol 1 vs. 2 mg/kg group, and twenty-five in the 2 vs. 3 mg/kg group. 

Results: There was no significant difference in the RCA image quality score, RCA length, diagnostic accuracy nor CNR with the use of the reduced dosing. 

Impact: Using reduced ferumoxytol dosing (1 or 2mg/kg), may lead to comparable image quality and diagnostic performance. The use of 2mg/kg lowers blood-T1 time to the extent that systolic imaging should not be precluded with the current 3D-IR Whole Heart Sequences. 

Keywords: Contrast Agents, Myocardium, MEMRI, Manganese, Mangafodipir, pig study, T tubuli, Ca2+ channel activity

Motivation: Evaluate manganese-enhanced MRI (MEMRI) for heart failure assessment.

Goal(s): Quantify the manganese uptake rate in the myocardium as an indicator of L-type calcium channel activity and T-tubule density.

Approach: A high temporally-resolved dynamic SatRec sequence was used to track the Mangafodipir bolus instead of using the less precise, but higher spatially-resolved, conventional T1 mapping method that was used before and after the manganese administration.

Results: Pigs have less dense T-tubule than humans leading to fewer L-type calcium channels and low Mn uptake in cardiomyocytes. Therefore, we believe that MEMRI can become a promising tool for assessing heart failure diseases in humans.

Impact: Since pigs are often used in preclinical research, there are important differences to be aware of. The low Mn uptake proved their less dense T-tubule, showing that MEMRI may be a useful tool for studying heart failure in humans.

Keywords: Novel Contrast Mechanisms, Prostate, Inversion Recovery

Motivation: Divided reverse Subtracted Inversion Recovery (drSIR) has shown potential for brain MRI but has not yet been applied to the prostate.

Goal(s): To produce prostate images with high $$$T_1$$$ contrast and highlight the junction between the peripheral and transitional zones by using two IR-TSE images with different inversion times (TIs).

Approach:  In healthy volunteers, the TIs that suppressed the peripheral and transitional zones as well as the tissue junction were determined, and the corresponding images were subtracted and divided pixelwise.

Results: High $$$T_1$$$ contrast between the prostate zones was achieved without contrast agents and subtle $$$T_1$$$ heterogeneities were observed.

Impact: High $$$T_1$$$ contrast with obvious distinction between the peripheral and the transitional zones of the prostate was achieved without contrast agents. The approach is likely to show lesions with high contrast and may improve the detection and delineation of tumors.

Keywords: Hybrid & Novel Systems Technology, Magnetization transfer, Magnetic particle spectroscopy, MPS, COMPASS, contrast agents, iron oxide based

Motivation: Contrast agents allow a significant improvement of MRI performance. Resotran is a new iron oxide-based and biocompatible MRI contrast agent that is now commercially available in Europe, which still needs to be characterized in more detail.  

Goal(s):  Classification of the performance of Resotran compared to Resovist.

Approach: Analyzation and characterization with various spectroscopic and imaging methods.

Results: Resotran shows a comparable performance to the former liver contrast agent Resovist. Furthermore, it was shown that Resotran is feasible as a tracer for the new imaging modality magnetic particle imaging (MPI). This is an important step towards paving the way for MPI in clinical routine.

Impact: In this work it is shown that the new clinically approved contrast agent Resotran shows a comparable performance as the well-known contrast agent Resovist by a detailed comparison applying different spectroscopic characterization methods.

Keywords: Contrast Agents, Liver, chronic diseases, fibrosis, precision MRI

Motivation: Hepatic fibrosis can develop in patients with any type of chronic liver disease which increase the risk of death for an estimated 1–2% of the world’s population.

Goal(s): Our goal is to develop novel MRI contrast agents for liver diseases which enable us to detect the liver diseases at early stages. 

Approach: We developed the novel MRI contrast agent for precision MRI. We achieved the molecular imaging on different animal models with liver diseases.

Results: Our results shows that our protein based MRI contrast agent can target the small lesions and fibrotic areas in the liver. 

Impact: The Protein based contrast agent with specific targeting capabilities is able to stage the liver diseases accurately.