Keywords: Relaxometry, Low-Field MRI, transmemebrane water exchange, cancer invasion/migration, bumetanide drug

Motivation: The transmembrane water exchange (t-Wex) in cancers was demonstrated modulating T₁ relaxation at ultra-low field. 

Goal(s): Our goal was to demonstrate T₁ changes under the administration of drugs that act on cell membrane transports.

Approach: U87 glioma cells sustained H₂O₂ stimuli before the administration of the bumetanide drug, a NKCC1 inhibitor. T₁ changes were measured by FFC-NMR.

Results: At very low field, by comparison to control cells (without H₂O₂), relaxation rates were found significantly lower under H₂O₂ stimuli which has been correlated to t-Wex acceleration and higher with the bumetanide addition, that suggests the slowdown of t-Wex.

Impact: Using the bumetanide drug, we show at ultra-low field, the potential of the relaxation T₁ as biomarker to evaluate the efficiency of drugs that can target t-Wex, a mechanism that has been connected to cancer invasion/migration pathophysiology

Keywords: Relaxometry, Metabolism, High-Field MRI；Magnetic Resonance Fingerprinting

Motivation: The monitoring of brain glucose metabolism plays an important role in the diagnosis of neurological diseases.

Goal(s): The glucose uptake and clearance in the mouse brain were monitored following intravenous administration of glucose using magnetic resonance fingerprinting.

Approach: A magnetic resonance fingerprinting imaging sequence was developed to simultaneously measure the T₁, T₂ and T_1ρ of tissue.

Results: With the intravenous administration of glucose, there was a rapid increase followed by a gradual decrease in R₁, R₂ and R_1ρ values in the brain.

Impact: The application of magnetic resonance fingerprinting in the study of brain glucose metabolism facilitates rapid and simultaneous measurement of multiple parameters, thereby yielding valuable information for the diagnosis of brain-related diseases.

Keywords: Novel Contrast Mechanisms, Microstructure, Multiple Sclerosis

Motivation: Myelin and iron carry significant roles in several neurodegenerative disease processes. The development of noninvasive imaging modalities for myelin and iron quantification and validation of these modalities are important steps in clinical MRI research.

Goal(s): MI-SSS is developed for the improved estimation of brain myelin and iron and here it is aimed to validate MI-SSS maps with histopathological quantification techniques.

Approach: An ex vivo whole brain is scanned; myelin and iron biomarkers maps are reconstructed and the results are correlated against histopathological findings.

Results: Both susceptibility maps showed significant correlation with histopathological myelin and iron quantifications presenting accurate performance of MI-SSS.

Impact: Myelin and iron quantification carry significant clinical importance for diagnosis and monitoring of neurodegenerative diseases. MI-SSS is developed to provide an improved and practical framework for this purpose. Here, the MI-SSS is validated against gold standard histopathological findings.

Keywords: Novel Contrast Mechanisms, Contrast Mechanisms

Motivation: As gold standard, MRI indeed matters in prostate imaging. The relative low image quality in ultra-low field MRI precludes its application in prostate imaging.

Goal(s): Our goal was to improve prostate image quality in ultra-low field MRI, particularly emphasizing the target prostate region.

Approach: We utilized an additional specially designed passive LC-resonator in imaging process.
 

Results: By using the LC-resonator, the prostate image quality in ultra-low field MRI was improved, giving a higher image contrast to the prostate region.

Impact: Adopting passive LC-resonator in imaging process is of highly cost effective, not only highlighting the target region, but offering a new imaging idea for other organs when it comes to bad SNR situations.  

Keywords: Multi-Contrast, Preclinical, Multinuclear

Motivation: Multinuclear contrast agents (CAs) may provide improved sensitivity and specificity for the detection/quantification of biomolecular processes.

Goal(s): To develop a multinuclear ¹H and ¹⁹F agent that shortens the T₁ relaxation times for both the ¹H and ¹⁹F signals only when hydrogen peroxide (H₂O₂) is present.

Approach: Developed the CA: Fe(II)-F₂H₄qp4 -- an iron(II) complex with a fluorinated quinol-containing macrocyclic ligand. This T₁-shortening CA is designed to activate only in the presence of H₂O₂.

Results: Initial phantom tests with an ¹H/¹⁹F frequency-selectable Inversion Recovery Look Locker sequence
 demonstrate a dual capability to quantify changes of both ¹H and ¹⁹F signal T₁ values.

Impact: The multinuclear Fe(II)-F₂H₄qp4 agent's ability to quantify changes of both ¹H and ¹⁹F signal T₁ values in an H₂O₂ environment improves the sensitivity and specificity to superoxide-related pathologies and may allow expanding to other biomarkers.

Keywords: Novel Contrast Mechanisms, Alzheimer's Disease, Blood-brain barrier

Motivation: Pneumonia is more prevalent in Alzheimer’s Disease (AD) patients than in healthy elderly people, which may be due to blood-brain barrier (BBB) vulnerability.

Goal(s): We assess whether filter exchange imaging (FEXI) can be used to understand the comorbid mechanisms occurring at the BBB with pneumonia and AD.

Approach: We apply the FEXI technique to a TgF344-AD rat model of AD with induced Streptococcus pneumoniae lung infection.

Results: FEXI detects significantly higher BBB water exchange in infected rats, with greater increase in the AD group, which significantly correlates to upregulation of hippocampus aquaporin-4 water channels, demonstrating the sensitivity of non-invasive FEXI to BBB alterations.

Impact: This work could be translated to a clinical study using filter exchange imaging to assess whether Alzheimer’s Disease patients suffering with pneumonia also exhibit worse blood-brain barrier alterations than patients without pneumonia and healthy elderly people.

Keywords: Novel Contrast Mechanisms, Contrast Mechanisms

Motivation: Neuromelanin-MRI contrast is a promising biomarker for Parkinson's disease, but still needs investigation as the biological and physical origins of the contrast are still unclear.

Goal(s): The objective was to unravel the mechanisms behind neuromelanin-MRI contrast, both biologically and physically, and to better understand the role of neuromelanin in Parkinson's disease.

Approach: We performed in vivo longitudinal neuromelanin-MRI coupled with quantitative multiparametric imaging on a rat model of Parkinson's disease based on accumulation of neuromelanin, with histological validation. 

Results: Results show that contrast increases with neuromelanin accumulation and decreases with neuronal loss. The contrast arises from T₁ reduction due to paramagnetic neuromelanin-iron complexes.

Impact: We provide first in vivo validation and better understanding of neuromelanin-MRI as a biomarker of neuronal loss in Parkinson's disease. Results also suggest a pathogenic threshold of neuromelanin accumulation triggering neurodegeneration. Investigating this hypothesis may lead to new therapeutic window.

Keywords: Novel Contrast Mechanisms, Multi-Contrast, Lung water, Heart failure, Translational studies

Motivation: Extravascular lung water is a feature in heart failure. Current lung water MRI methods cannot distinguish between intravascular and extravascular fluid, and therefore cannot fully isolate the pathology.

Goal(s): To isolate and quantify extravascular lung water by developing a dual-contrast extracellular volume (ECV) method, leveraging different extracellular compartmentalization of gadolinium and ferumoxytol.

Approach: We calculated ECV_{extravascular}=ECV_gadolinium-ECV_ferumoxytol from lung T1-maps with native, gadolinium and ferumoxytol contrast. Validation was performed in porcine models of increased extravascular and intravascular lung water.

Results: As expected, ECV_{extravascular} differed between baseline and the extravascular intervention (27±4.1% vs 32±1.6%, p=0.005), but not for the intravascular model (22±4.7% vs 22±4.4%, p=0.91).

Impact: Dual contrast extracellular volume measurements, leveraging the different compartment uptakes of gadolinium and ferumoxytol contrasts, is a promising method for extravascular lung water quantification, and may enable mechanistic studies of lung water accumulation in patients with dyspnea.

Keywords: Relaxometry, Contrast Mechanisms, Paramagnetic Relaxation Enhancement; Rotational Correlation Time; Clinical MR Relaxometry

Motivation: This study exploits the underexplored potential of paramagnetic relaxation enhancement (PRE) in clinical MR scanners to characterize molecular interactions and tissue microenvironments in vivo, leveraging Gadolinium-based contrast agents (GBCAs).

Goal(s): Develop and validate methodology for estimating Gadolinium-based contrast agent (GBCA) correlation time via relaxivity ratio measurements at 1.5 and 3 Tesla.

Approach: Applying relaxation models, we devised a dictionary-matching framework correlating GBCA relaxivities with correlation times, and validated our methods using phantom experiments.

Results: Our framework accurately estimates GBCA correlation times at a single field strength showing <5% error (1.5T to 3T) and <11% (3T to 1.5T) in cross-field relaxivity predictions.

Impact: This framework leverages MR Relaxometry for precise estimation of GBCA rotational correlation time at single field strengths, offering insights in tissue characteristics. There is significant potential to improve tumor imaging and diagnosis through insights into pH, viscosity, and protein interactions .

Keywords: Epilepsy, MR Fingerprinting, Surgery, Focal cortical dysplasia

Motivation: Focal cortical dysplasia (FCD) is a common pathology in medically intractable focal epilepsy. Detecting and subtyping FCD through visual inspection of conventional MRI can be challenging.

Goal(s): We aimed to develop a multiparametric, quantitative approach for FCD characterization, based on MR fingerprinting (MRF).

Approach: High-resolution 3D MRF scans were performed in 33 epilepsy patients with FCD, 60 normal controls and 26 disease controls. A machine-learning (ML) framework based on MRF was developed to automatically classify FCD from normal cortex and separating FCD subtypes.

Results: MRF-based ML models showed high accuracies, with performances superior to the yields of clinical review.

Impact: Our approach contributes to noninvasive epilepsy presurgical evaluation, as well as an integrated clinical-pathological-imaging understanding of the FCD spectrum.

Keywords: Novel Contrast Mechanisms, Brain, blood brain barrier permeability to water, oxygen extraction fraction, neuromyelitis optica spectrum disorder, multiple sclerosis

Motivation: Accurate differentiation of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is essential for treatment decisions and thus affects prognosis.

Goal(s): This study aimed to determine the differences of MS and NMOSD using physiological and quantitative MRI.

Approach: blood brain barrier permeability to water (PS) and oxygen extraction fraction (OEF) of all subjects were measured by physiological and quantitative MRI.

Results: The results showed that compared with healthy subjects, water PS was significantly higher in NMOSD patients, while OEF was significantly lower in MS patients. In addition, OEF was also significantly different between NMOSD patients and MS patients.

Impact: Our study demonstrated that BBB permeability to water and whole-brain oxygen extraction fraction (OEF) might be potential imaging indicators for NMOSD and MS, respectively. In addition, OEF is the key to distinguish MS from NMOSD.

Keywords: Multi-Contrast, Oxygenation, Brain Tumors, Cancer, Oxygen Extraction Fraction, hybrid MR-PET

Motivation: Multi-contrast GE/SE acquisitions provide versatile, simultaneously acquired MR parameters, with fast, non-invasive OEF quantification proving potentially exceptionally valuable in clinical practice.

Goal(s): The tumour characterisation capability of 10-echo GE-SE EPIK-derived MR parameters was evaluated in standardised tumour VOIs compared to healthy brain tissue.

Approach: A full-brain 2-minute protocol was acquired from 18 tumour patients during hybrid 3T MR and FET-PET acquisitions. Quantified MR parameters were analyzed in tumour VOIs defined by FET-PET.

Results: The increased T₂/T₂* values and decreased vCBV/OEF obtained using 2-minute GE-SE EPIK acquisitions were in agreement with literature values.

Impact: Whole-brain T₂, T₂*, vCBV, and OEF quantification can be obtained within a 2-minute TA using 10-echo GE-SE EPIK MRI, revealing changes in tumour VOIs in agreement with literature values, potentially providing fast clinical access to MR parameters, especially OEF.

Keywords: Novel Contrast Mechanisms, Radiotherapy, MR-Linac, radiation dosimetry

Motivation: Direct imaging of radiation beam effects could enable more accurate dosimetry and in vivo dose verification.

Goal(s): Our goal was to detect immediate changes in T₁ relaxation due to water radiolysis induced oxygen depletion.

Approach: We used dynamic T₁ mapping on an MR-Linac to simultaneously irradiate and image water phantoms.

Results: We observed real-time changes in T₁ with a T₁/Dose slope of 0.71 ms/Gy. The current sensitivity limit was estimated to be 3 Gy for a 10 min scan. Three-dimensional spatial patterns in T₁ were consistent with the predicted dose profile.

Impact: Real-time visualization of radiation beam effects using quantitative T₁ mapping may enable new radiation dosimetry methods. This study may lead to volumetric in vivo dose verification and imaging of transient oxygen depletion in high dose rate (“FLASH”) radiotherapy.

Keywords: Microstructure, Susceptibility

Motivation: To develop noninvasive methods to interrogate magnetic microstructure.

Goal(s): To test whether the strong collision approximation can accurately characterize microstructure of known geometry and magnetic susceptibility from gradient-echo and spin-echo signals.

Approach: Experimental data were acquired from phantoms containing polystyrene microbeads of 10$$$\mu$$$m, 20$$$\mu$$$m and 40$$$\mu$$$m diameter suspended in gadolinium-doped gelatin. Data were fitted using a published model based on the strong collision approximation and a lookup table prepared from Monte Carlo simulations.

Results: The strong collision approximation overestimated bead size and underestimated magnetic susceptibility from gradient-echo data. For spin-echo data, it yielded poor estimates of susceptibility and was insensitive to bead size.

Impact: The strong collision approximation is a non-perturbative approach for predicting gradient-echo and spin-echo signals in the presence of magnetic microstructure. It employs the Krogh construction and a simplified diffusion propagator. We show how those simplifications affect estimates of microstructural parameters.

Keywords: Relaxometry, Relaxometry, T1 Relaxation, Magnetization Transfer, Orientation Dependence

Motivation: Studies on the orientation dependence of T₁  have led to contradictory observations, indicating that this effect is not well understood.

Goal(s): Our primary objective was to meticulously explore the orientation dependency of T₁ under precisely controlled and stable conditions.

Approach: Comprehensive T₁ (inversion recovery) and magnetization-transfer (MT) experiments were performed in fixed spinal-cord samples, with systematic variation of the fiber-to-field angle θ_FB .

Results: No relevant T₁  variation with θ_FB  was observed in the IR experiments. However, a clear orientation dependence was consistently observed in all MT experiments,

Impact: Precise quantitative MR measurements in spinal cord with varying fiber-to-field angle showed no consistent orientation dependence of T₁  but a clear effect for the MT saturation, indicating the MT effects may be responsible for the previously observed T₁ anisotropy.

Keywords: Microstructure, DSC & DCE Perfusion, blood-brain barrier; Alzheimer's disease; dementia with Lewy bodies

Motivation: Transfer rate of contrast agent and water plays complementary role in assessing the integrity of blood-brain barrier, however there is currently no means of evaluating them simultaneously in dementia patients.

Goal(s): We aimed to develop a new pharmacokinetic model to comprehensively evaluate the blood-brain barrier damage in dementia patients.

Approach: Transfer rate of contrast agent and water was calculated based on a new pharmacokinetic model by simultaneous fitting of the Bloch–McConnell equation and the Patlak model. 

Results: The proposed model was able to exhibit distinct patterns of blood-brain barrier damage in different types of dementia, which was significantly associated with cognitive impairment.

Impact: The transfer rate of contrast agent and water based on water exchange DCE-MRI demonstrated distinct patterns of blood-brain barrier damage in patients with Alzheimer’s disease and dementia with Lewy bodies, providing promising new non-invasive imaging biomarkers for dementia.

Keywords: Microstructure, Quantitative Imaging, Iron, Substantia nigra, R2*

Motivation: Dopaminergic neurons require iron for their function but suffer from iron overload in age.

Goal(s): To non-invasively monitor the age-related iron accumulation in dopaminergic neurons, we investigated mechanisms of iron-induced MR contrast in the substantia nigra across the lifespan.

Approach: We combined quantitative MRI, X-ray fluorescence imaging and biophysical modelling in a unique animal model: ethically collected postmortem chimpanzee brains.

Results:  The iron load of dopaminergic neurons and the effective transverse relaxation rates in the substantia nigra increased with age. The biophysical model accurately links the relaxation rate to the iron load and neuronal density, which demonstrated its suitability for ages above puberty.

Impact: Monitoring cell-specific iron concentrations of dopaminergic neurons and neuronal densities in the substantia nigra throughout the lifespan holds potential of an early neuroimaging biomarker for Parkinson’s disease.

Keywords: Relaxometry, Relaxometry, Water exchange, diffusion physics

Motivation: Transmembrane water exchange in brain tissue is a process often modelled via the first order kinetics reaction (1OKR) expression. However, this expression does not account for diffusion dynamics, suggesting it is not suitable to describe diffusion-driven exchange.

Goal(s): Assess the difference between the 1OKR expression and the exchange fraction derived from a generally defined system.

Approach: The exchange fraction was derived considering geometry, and compartment-specific relaxation processes of a system via the diffusion-reaction equation.

Results: The derived exchange fraction features a multi-exponential recovery at short times and a mono-exponential decay at long times, both of which are not captured by the 1OKR expression.

Impact: The two additional features of the exchange fraction found in this work provide additional insight on a system’s microstructure and properties. This expression can therefore be the basis of new biophysical models which more accurately describe the water exchange process.

Keywords: Relaxometry, Metabolism, Oxygen metabolism

Motivation: Factoring out venous cerebral blood volume (vCBV) and oxygen extraction fraction (OEF) from the relaxation of R2’ poses a significant challenge.

Goal(s): We combined robust measurements of R2’ relaxation from GE-SE EPIK and perfusion from VSI-ASL with a flow-diffusion model of oxygen transport to improve estimation of vCBV and OEF.

Approach: The proposed method was tested in normoxia, hyperoxia and hypercapnia against validated TRUST measurements of OEF.

Results: Maps of OEF and vCBV accurately depicted the oxygen metabolism at baseline as well as during the gas challenges without the need of any calibration, with high resolution and within reasonable acquisition time.  

Impact: The integration of the oxygen flow-diffusion model with GE-SE EPIK measurements of R2’ relaxation and VSI-ASL measurements of perfusion gives high resolution parametric maps of oxygen metabolism within reasonable acquisition time, ultimately reducing the gap between research and clinical practise. 

Keywords: Novel Contrast Mechanisms, Perfusion, blood volume, oxygenation, relaxometry

Motivation: Most MR methods for quantifying microvascular properties involve the injection of exogenous contrast agents (CA).

Goal(s): We propose an innovative MRI method that simultaneously maps the deoxygenated cerebral blood volume (CBV), microvascular geometry (averaged vessel radius), and relaxometry (T₁&T₂) without CA injection.
 

Approach: Acquisitions are made using a multi-echo, phase-cycled, bSSFP-sequence acquired in transient and pseudo-steady-state regimes. Reconstruction of the maps is made under the MRFingerprinting framework using realistic 3D microvessel representations. Magnetic field distributions (B₁&B₀) are also taken into account.

Results: Preliminary results on five healthy volunteers are in line with previous measurements made with MRF and PWI with gadolinium injection.

Impact: We propose a contrast-free quantification technique of microvascular properties and relaxation times. It could be useful for functional experiments as well as clinical investigations of several cerebrovascular pathologies including stroke and cancer.