The DW-SSFP sequence is useful to attain strong diffusion-weighting on clinical systems while keeping a short repetition time. However, its analytical model does not account for the echo time. Using a 3D EPG model, we show that the echo time plays an important role, and that it cannot be neglected. We then provide a new method to jointly estimate T₂ and the diffusion tensor on an ex-vivo fetal brain at 3 T.

In this work, we perform Monte Carlo simulations of diffusion in the extra-axonal space segmented from realistic 3D electron microscopy substrates. Simulations in sham and TBI rat brains confirm the universality of the power-law functional form of the axial and radial time-dependent diffusion $$$D^{\parallel,\perp}(t)$$$ and kurtosis $$$K^{\parallel,\perp}(t)$$$. We characterize the changes caused by TBI, finding that the dependence of long-time asysmptote $$$D^{\perp}_\infty$$$ on the extra-axonal volume fraction follows Archie's law. We also validate the theoretically predicted relationship between the power-law tails of $$$D(t)$$$ and $$$K(t)$$$. 

In hyperpolarized [1-¹³C]pyruvate MRI of the brain, pyruvate-to-bicarbonate conversion, representing oxidative metabolism, is detected at low levels, despite the highly oxidative metabolism of the brain. We sought to determine the effect of lactate excitation on bicarbonate detection in healthy rats imaged in a cross-over fashion (lactate flip angle = 90° or 0°). In the brain, the bicarbonate signal-to-noise ratio increased 65 % when lactate was not excited. This effect was not observed in the heart, kidneys or liver. Collectively, our data show that lactate saturation limits bicarbonate detection in the brain solely, which has implications for study designs.

Parallel imaging can aid hyperpolarized ¹³C MRI in extracting more information in the limited time window of the hyperpolarized signal. Using a dedicated, flexible ¹³C receive coil design with coupling coefficients matched for both ¹³C and ²³Na, sensitivity profiles for reconstruction can be acquired at the ²³Na frequency. We demonstrate this method in two hyperpolarized in vivo experiments involving pig kidneys and human brain using a two-times accelerated 3D blipped stack-of-spirals sequence with dual-resolution. The results show good SNR, coverage, and resolution. The method is promising for integrating and automating parallel imaging for hyperpolarized ¹³C MRI.

Hyperpolarized [1-13C] fumarate has been shown to be a reliable imaging biomarker for monitoring cellular necrosis with conversion of [1-13C]fumarate to [1-13C]malate via Fumarate hydratase. However, the inherently low 13C-sensitivity limits biomedical applications with a need for accessible and low-cost hyperpolarization methods.

In this abstract we show that parahydrogen-induced polarization methods can overcome these limitations by providing highly polarized and purified [1-13C]fumarate as a non-toxic perfusion agent with the capabilities of acting as a biomarker of cell necrosis in metabolic 13C MRI.

The PHIP-X methodology is a novel approach to hyperpolarize nuclei from specific molecules that could function as contrast agents in metabolic MRI. PHIP-X combines the strong polarization of hydrogenative PHIP with the broad applicability of proton exchange and opens up the variety of potential hyperpolarizable biomolecules. The presented experimental setup facilitates the application of pH₂ pressures up to 30 bar and well-defined external magnetic fields up to 80 mT. Using this setup allowed to hyperpolarize glucose (830 mM) and achieved increasing polarization with increasing the pressure from 10 bar to 20 bar (molar polarization was more than doubled).

We determined day-to-day variation and intra-session reproducibility of ³¹P-MRS-based hepatic phosphorus metabolite quantification. To this end, we compared a standard single loop with a custom-created quadrature surface coil. Absolute concentrations of γ-adenosine triphosphate and inorganic phosphate were assessed in 7 volunteers with both coils. Both coils showed comparable day-to-day and intra-session CVs < 10 %. Metabolite concentrations determined by the two coils were similar. Therefore, both coils yield robust absolute concentrations of hepatic phosphorous metabolites. The quadrature coil allows measurements at a higher distance from the coil which can be important for the application in obese patients.

Exploring spatial distribution of intra- and extramyocellular lipids linked to the orientation of muscle fibers is complex. We used a magnetic resonance spectroscopic imaging (MRSI) technique with a spiral encoding of k-t space and diffusion imaging tractography at 3T to reveal possible concomitant factors. The IMCL preponderance index, exploiting the spectroscopic dimension and proposed in this study, highlights interesting and relevant patterns in some calf muscle heads.

Previous ¹²⁹Xe-MRI binning analysis techniques assumed normal distributions or relied on a Box-Cox transformation. Adapting these binning methods to account for known covariates of lung function and structure, such as age and height, was not straightforward. To account for these limitations, a new binning method is proposed here that uses the same modeling techniques used to increase sensitivity and specificity in spirometry and diffusing capacity for carbon monoxide (DLCO). By accounting for MRI image distribution shapes and covariates, healthy representative data distributions are better modelled and can permit increased sensitivity and specificity, particularly for early cardiopulmonary disease progression.

¹²⁹Xe-MRI can quantify abnormal gas-exchange by defining thresholds derived from voxel-level gas-exchange distributions in healthy subjects. Previous studies assumed a constant healthy distribution independent of age. By fitting to Box-Cox Power Exponential distributions, normal distributions cannot be assumed, and the distributions vary significantly with age. The effect size of age (5-69 years) on healthy ventilation, barrier-uptake, and red-blood cell to barrier (ratio) signal distributions were 14 to 57%. Thus, age and distribution shape should be considered when defining reference distributions for gas-exchange metrics. By accounting for age-dependent variations, the reference distributions abnormal thresholds could be narrowed.

Hyperpolarized (HP) ¹²⁹Xe diffusion imaging, including the apparent diffusion coefficient (ADC) and more sophisticated diffusion morphometry, can assess microstructural dimensions of the acinar airspace. In diseases characterized by alveolar destruction (eg, emphysema), these parameters strongly indicate disease severity. Here, a time-efficient, 2D-spiral diffusion sequence was developed and compared to a conventional GRE-based sequence in a free-diffusion phantom, wild-type mice, a and a transgenic mouse model of lung fibrosis that develops emphysema as a comorbidity. Both sequences provided comparable SNR, ADC values, and morphometry metrics, indicating spiral sequences can assess airspace size in mice, while making efficient use of HP magnetization.

Hyperpolarized ¹²⁹Xe gas MRI provides a spatially resolved method of monitoring gas exchange function in the lungs via 3D reconstruction of RBC/gas and barrier/gas signals. However, the strength of these signals is affected by patient hemoglobin concentration (Hgb). Thus, correcting for Hgb is important for establishing normative healthy reference distributions and accurately assessing the degree of gas exchange impairment. Here, we use a 1D physical diffusion model to establish Hgb-dependent correction factors to standardize gas exchange MRI relative to a fixed Hgb value. This correction can result in substantial changes in the visualization and quantification of gas exchange MRI.

Parahydrogen-induced polarization relayed via proton exchange (PHIP-X) is a new method to hyperpolarize a variety of molecules that participate in suitable fast proton exchange with allyl alcohol. The combination of the wide applicability of polarization-transfer via proton exchange and the strong polarization obtained using hydrogenative of PHIP opens up new avenues to hyperpolarize biological molecules such as glucose, lactate and pyruvate. Hence, PHIP-X provides a promisingnew platform for potential applications in metabolic MRI.

Dissolution DNP (dDNP) is an alternative for hyperpolarizing ¹²⁹Xe to the well acknowledged method spin exchange optical pumping (SEOP). As opposed to SEOP, DNP takes place in the solid state at very low temperatures. Therefore, it can potentially produce a large volume of hyperpolarized gas after dissolution. In this study, by implementing a new way of preparing the sample, we ease the overall process and establish a superior incorporation of the gas atoms into the solvent. Additionally, due to a surprisingly short radical electron T₁, we show that a higher polarization was achieved by applying microwave frequency modulation. 

In this study, we prepared a ¹⁵N-enriched analog of NAD⁺ (N-methyl nicotinamide = MNA⁺) and demonstrated that it undergoes reduction by sodium dithionate to form MNAH. The ¹⁵N chemical shifts of the oxidized and reduced forms differ by 124.2ppm. DNP of MNA⁺ followed by dissolution and ¹⁵N NMR showed a favorable T₁ relaxation time of 130s at 1T and 50s at 3T. Deuteration of the methyl protons only increased the T₁ of ¹⁵N by ~10s. The long T₁ of ¹⁵N in these NAD⁺/NADH mimetics and the large chemical shift difference offer the exciting potential for their use as redox sensors.

²³Na-MRI offers the possibility for non-invasive quantification of the sodium concentration in-vivo. The obtained functional information can provide interesting insights into the degeneration state of the human intervertebral discs¹ (IVDs). The presented work thus aimed to quantify the tissue sodium concentration (TSC) in the human intervertebral discs via ²³Na-MRI at 7T and to compare the obtained concentrations for two healthy volunteers after the course of one year. The estimate average concentration for all IVDs of both volunteers was found to be (96.5±8.8)mM and (113.6±9.5)mM, respectively.

In this work, a 2D radial ²³Na sequence with half-VERSE pulses was developed to reduce SAR and achieve ultra-short TEs. Simulations and measurements of the slice profiles showed good agreement between full- and half-VERSE pulses with a maximal deviation in the FWHM of 7%.

In measurements, the TE_min was reduced from 1.41ms to 0.1ms by the use of half- instead of full-VERSE pulses. This resulted in an SNR gain of up to 18% in phantom, 7% in brain and 26% in calf measurements.

Last, rapid single-slice ²³Na images (2.9x2.9x12mm³) were obtained in a clinically feasible acquisition time of 2:56min.

The repeatability of sodium (²³Na) MRI measures must be understood to allow for its application in clinical studies of patient groups or response to therapy. A series of ²³Na scans were performed on the calf of healthy subjects, this included a  3D GRE ²³Na scan and phase sensitive B₁ mapping to measure tissue sodium concentration (TSC). Subjects were scanned twice for assessment of repeatability of measures. A multi echo UTE scan was used to measure the T₂* decay. TSC was shown to have a coefficient of variation of 16±4 % between visits and the bi-exponential decay curve was characterized.

Deuterium magnetic resonance measurements are of growing interest in the field of metabolic imaging. Four subjects were loaded with D₂O to ~1.5% enrichment over a 6-week period for a parallel study of immune cell proteomics. We report T₁ and T₂^* relaxation times of deuterium in HDO measured from cerebral spinal fluid (CSF), white matter (WM) and grey matter (GM) in vivo, using a 7T Philips Achieva scanner with a dual-tuned ²H/¹H birdcage coil. ²H T₁ values are significantly shorter than corresponding values for ¹H in H₂O, due to the quadrupolar ²H relaxation, whilst T₂* values are comparable to ¹H values.

²H-MRS is a novel method of imaging flux through metabolic pathways. Here, we show that ²H-MRS can be used to probe the isocitrate dehydrogenase 1 mutation (IDHmut), which catalyzes production of the oncometabolite 2-hydroxyglutarate (2-HG) in low-grade gliomas. Our results indicate that 2-HG production from [3,3’-²H]-α-KG can be specifically observed in IDHmut cells. Importantly, treatment with an IDHmut inhibitor, which is in clinical trials for low-grade glioma patients, results in a significant reduction in 2-HG production from [3,3’-²H]-α-KG in IDHmut cells. Our results point to the potential of [3,3’-²H]-α-KG as a probe of glioma IDHmut status and response to therapy.

Deuterium magnetic resonance imaging and spectroscopy at 7T has been used to follow the deuterium concentration in the brain over an ~eight-hour period while subjects orally-loaded with D₂O to 100x natural abundance. Changes in deuterium concentration of ~ 0.1% can be readily monitored in ²H spectra acquired in 1 minute and images acquired in 7.5 minutes. The change in deuterium concentration estimated from ²H spectra is in agreement with the value calculated from cumulative D₂O dose and body mass and the signal changes measured from ROIs in the brain have similar time-courses, with relative signal strengths dictated by T₂*-weighting.

Deuterium metabolic imaging (DMI) has been proposed as a means to probe glucose uptake and metabolism. It is expected that DMI will reveal important changes in cancer and neurodegeneration. We constructed a dual-tuned 7T ²H/¹H array coil and assessed appropriate RF power limits by EM modelling. The coil performance has been assessed with phantom scans on a D₂O-enriched agar phantom. We are now ready to start human in vivo scanning.

¹H-[¹³C] NMR spectroscopy is a powerful tool to study metabolic information in human brain. At 7T, the proton-observed carbon-edited (POCE) method provides high sensitivity and improved spectral resolution. However, the application in human brain has more constraints due to high RF power deposition at 7T. In this study, we investigated the performance of the STEAM-based POCE sequence without decoupling to reduce the RF power. The phantom experiments and the Monte Carlo simulations demonstrated high-quality ¹H-[¹³C] MR spectra and the accurate quantification of ¹³C-labeled glutamate and glutamine without decoupling at 7T.

The focus of this work is on the optimization of fluorine-19 enabled SPGR, bSSFP, and phase cycled bSSFP (bSSFP-C) pulse sequence parameters to improve signal acquisition efficiency for perfluoropolyether (PFPE) at 3T with a multi-channel coil. Bloch simulations and subsequent experimental validation were performed to determine the parameters to maximize the SNR-efficiency for each sequence. Acquisitions of the optimized SPGR, bSSFP, and bSSFP-C were then assessed for their achieved SNR-efficiency. bSSFP and bSSFP-C demonstrated increased sensitivity compared to SPGR. Feasibility of bSSFP-C with parallel imaging demonstrated the ability to reduce scan times by 2-fold without compromising the qualitative image quality. 

Phosphorus (³¹P) nuclear magnetic resonance spectroscopy (NMR) has the potential to play a valuable role in the characterization of myelin due to the concentration of ³¹P present in myelin phospholipids. This study demonstrates the feasibility of detecting ³¹P through cross polarization (CP) and magnetization transfer (MT) from hydrogen in preserved murine spinal cord and fresh porcine brain. The results demonstrate the detection of myelin phospholipids through these NMR techniques and provide compelling proof of concept for the potential applicability of MT-CP in ³¹P MRI for non-ambiguous myelin characterization in vivo.

Gadolinium-enhanced imaging provides valuable information in clinical practice. Concerns raised by gadolinium depositions favors strategies reducing injected doses in patients requiring repeated scans. We designed four phantoms containing serial dilutions of four gadolinium-based contrast agents to compare their efficacy for low-Gd concentration detection in clinically used MR sequences, based on signal intensity and contrast-to-noise ratio. We performed a preliminary study comparing T1-TSE, FLAIR and FLAIR with optimized parameters on these phantoms. The optimized FLAIR sequence shows an efficient detection of low concentrations, in particular using gadobutrol or gadoteridol.

Brain data with high grade glioma were acquired with a 3D multiparameter mapping sequence and reconstructed with a novel deep learning based method (DL Recon). Synthetic images created from maps fitted to the reconstructed images were rated by experienced radiologists for image quality and diagnostic utility. Images from the DL Recon workflow consistently rated equal to or better than those created from conventional reconstruction. We find that the SNR and resolution benefits of 3D DL Recon extend to improve the resulting relaxation maps and subsequent synthetic images.

Simultaneous measurements of R₂ and R₂’ using the Gradient Echo Sampling of a Spin Echo (GESSE) sequence were made at multiple spin echo times in four volunteers. Secondary measurements of R₂ and R₂* were made using classical Spin Echo and Gradient Echo approaches. The variation in measured relaxation rates are explored and show a general overestimation of transverse relaxation in white and grey matter when measured with GESSE suggesting a lack of complexity in the model used to describe the GESSE signal.

DWI of the pancreas is challenging due to artifacts from physiologic motion, image distortion, and blurring, but has promising applications in pancreatic cancer detection. We conducted a pilot study of pancreatic DWI comparing single-shot and multi-shot EPI protocols as well as multi-shot EPI protocols with and without a new commercially available deep learning (DL) based denoising reconstruction method. Image quality was subjectively scored with key metrics. Multi-shot EPI reduced perceived distortion within the pancreatic bed, while the combination of multi-shot EPI and DL reconstruction subjectively reduced noise.

Filter-exchange spectroscopy (FEXSY) and imaging (FEXI) are sensitive to transmembrane water exchange, which is commonly altered during cell death¹. Yeast cells in different permeabilization stages were studied with FEXI, DWI and CFDA-AM/ propidium iodide (PI) staining using flow cytometry. Cell populations with 3.8% PI positive staining had 44% increased AXR, but unchanged ADC. At 33% nonvital cells, detection of AXR became unreliable and ADC increased. In vivo FEXI and DWI in EL4 lymphoma, with H&E-confirmed necrotic tumor cells and edema, showed AXR and ADC variations across the tumor, possibly due to differing vitality cell stages.

IVIM and DTI techniques are both sensitive to a variety of muscle disorders. Their combination can give a more complete description of ordered diffusion processes and perfusion. Model-based reconstruction can overcome many short-comings of image-based fitting such as Rician noise bias or low SNR. In this study we investigate the feasibility of model-based IVIM-DTI reconstruction in skeletal muscle, a low-perfused tissue. Results were compared to image-based least-square fitting. The parameter maps show more anatomical detail with model-based reconstruction. The mean parameter values are comparable to image-based fitting. Model-based reconstruction is sensitive to subtle changes after exercise in the underlying parameters.

Free water (FW) imaging is a diffusion-weighted MRI technique that differentiates extracellular from intracellular water compartments. Increased FW fraction is generally associated with neuroinflammation. However, establishment of a direct link between FW and biomarkers of neuroinflammation in human studies is not feasible. In this work, we use MRSI to find correlations between FW and metabolic biomarkers of inflammation in HIV infected individuals. Our results show that FW had the most significant positive correlations with myo-inositol, a strong biomarker of gliosis and inflammation. This corroborates previous findings that elevated FW can be interpreted as a sign of inflammation in the brain.

We provide longitudinal relaxation measurements of hyperpolarized (HP) ¹²⁹Xe gas dissolved in a variety of solvents at both low and high magnetic field strengths. The method of measuring T₁ presented here is less sensitive than more commonly used methods to RF flip angle miscalibration, which has caused the significant variation in dissolved-phase ¹²⁹Xe T₁ values reported in the past. A field dependent study of gas depolarization by hollow membrane fibers commonly used to dissolve xenon in blood or other solvents is also included, which provides insight to experimental limitations on their use in both field regimes.

Hyperpolarized (HP) ¹³C MRI requires advanced pulse sequences to capture the dynamic, localized metabolic information. We developed an echo planar spectroscopic imaging (EPSI) pulse sequence incorporating multi-band spectral-spatial radiofrequency (SSRF) pulses for rapid and efficient HP ¹³C MRI on a new cryogen-free simultaneous PET/MR molecular imaging platform with compact footprint. Excitation profiles were measured in phantoms, and the SSRF-EPSI sequence was tested in rats using two HP ¹³C probes. We also obtained simultaneous ¹⁸F-FDG-PET data for comparison. In conclusion, advanced ¹³C SSRF imaging approaches are feasible on the new PET/MR platform, facilitating direct comparison with PET.

In Xenon Polarization Transfer Constant (XTC) imaging, saturation pulses are applied at DP Xe frequencies for red blood cell (RBC) and tissue plasma (TP), but, due to their high power, are not perfectly selective, often depolarizing both DP frequencies instead of only the one intended. We used XTC spectroscopy to explore how various saturation pulse parameters, primarily pulse power, affects saturation selectivity. The generated graphs plot depolarization as a function of saturation frequency. They demonstrate that as pulse power increases, the contribution of gas-phase depolarization due to off-resonance saturation increases, compromising selectivity. 

The choice of repetition time (TR) in MR spectroscopy studies is widely debated. A shorter TR results in more clinically acceptable scan times, however due to T1 effects, the metabolite concentrations are reduced. We used semi-LASER MRS to compare the SNR and absolute metabolite concentrations for TR=2,5 and 8s. We demonstrate it is possible to achieve similar SNR and scan time using a TR of 5s with half the acquisitions compared to a TR of 2s, where the metabolite concentrations are 20% lower. Using a TR of 5s for any MRS study is feasible and recommended to minimize T1 effects.

3D bioprinted scaffolds are one of the most novel and promising tissue regenerative therapeutics currently in development (e.g. to repair damaged cardiac tissue). Validation of correct scaffold placement and retention post-implantation is essential, but it is challenging to visualize scaffolds in-vivo given their similar material properties to native tissue. In this study, a T1-reducing contrast agent, MnPNH₂, was utilized to create an MR-trackable, bioprinted scaffold. In-vitro and in-vivo results confirmed the novel scaffold provided an environment conducive to cell growth and offered significant bright contrast for post-implantation scaffold monitoring in rats.        

Modifications to the CF₃ side-group of teriflunomide were made to improve its detection by ¹⁹F MRI. Pentafluorosulfanyl (SF₅) was shown to be a superior alternative to CF₃. The SNR efficiency of three ¹⁹F MRI methods showed that within a biological environment, SF₅-substitutions gave the highest SNR efficiency in combination with an ultrashort echo-time (UTE) MRI method. Chemical modifications did not hamper biological activity but SF₅-TF was more effective to inhibit T cell proliferation, indicating better anti-inflammatory activity. This study proposes SF₅ as a novel superior ¹⁹F MR reporter group for the drug teriflunomide.

MRI reporters for hyperpolarized ¹²⁹Xe CEST need further improvement in order to sufficiently outcompete the intrinsic loss of hyperpolarization appearing under in vivo conditions.  This study opens up a possibility by accelerating the CEST build-up for the well-known Xe host CrA-ma by two orders of magnitude.  We designed a liposome decorated with a CrA-lipopeptide. To avoid inefficiency from back exchange, the lipopeptide fraction should be kept relatively low (e.g., 2 mol%). Complete saturation transfer could be easily achieved for maximum possible image contrast in ¹²⁹Xe MRI scans. This study pinpoints a large flexibility for designing  powerful HyperCEST agents.

Recently, it was shown that hyperCEST enables detection of microbubbles at clinically relevant ultrasound doses. Nanodroplets filled with low-boiling point perfluorocarbons are precursors of microbubbles. Because the chemical shift of xenon in liquid-phase perfluorocarbon nanodroplets is different than that in gas-phase microbubbles, hyperCEST detection of these nanodroplets could enable MR detection of their phase-change upon ultrasound activation. To this end, here we investigate if perfluorocarbon nanodroplets can be used as hyperCEST agent, first in vitro and then in vivo.

D-glucose is proposed as a cheap biodegradable alternative to gadolinium-based contrast agents. By performing glucoCEST imaging during and after administration of glucose, an approach referred to as dynamic glucose-enhanced (DGE) MRI, information about glucose delivery and uptake can be obtained. However, the small DGE signal changes at 3 T can easily be corrupted by motion. Furthermore, standard retrospective motion correction may erroneously alter true DGE signal, which may lead to misinterpretation. We designed a numerical head phantom that can be used for validation of motion correction and providing insight into the corresponding effects in vivo. 

CEST MRI suffers from long acquisition times and/or limited volume coverage. Here we suggest using a spatio-temporal variable density Poisson disk design for whole brain APTw snapshot CEST. This enabled us to acquire 1.3 mm isotropic whole brain APTw CEST maps in under 2 minutes. All the reconstruction and necessary adjustment steps were implemented within the scanner software, enabling a push-button B0-corrected CEST measurement.

MRI and MRS are finding more and more their way into forensic medicine. Unlike in vivo measurements, however, the temperature of cadavers in forensic medicine varies considerably and affects the performed measurement. The present study investigated how well published calibrations measured in vivo or in phantoms are suited for postmortem MRS thermometry. Postmortem MRS thermometry would allow to estimate and possibly correct the effects of the local temperature in a forensic setting. The study reveals that despite strong postmortem changes, a reliable estimation of the local temperature over up to 60 hours after death is possible with available temperature calibrations.

MR-guided hyperthermia at low magnetic field is challenging due to the inherently low SNR, which typically calls for multiple signal averages. Dedicated coils are crucial at this field regime, to maximise signal acquisition. In this study we built a custom RF coil which integrates a water-based heating system to reproduce hyperthermia conditions in hands. Using a fast T₁-mapping sequence, we could successfully monitor the temperature variations generated in a phantom over 120min. A first in vivo employment in a volunteer’s hand at room temperature was also shown, achieving a spatial and temporal resolution compatible with hyperthermia requirements.

MR thermometry using dual-echo single-shot EPI was evaluated in a phantom. Dual-echo EPI resulted in better temperature stabilities than the single echo acquisitions. This sequence was successfully combined with SMS, which also resulted in higher temperature stability than the single echo acquisitions.