1H MR Imaging Research Articles

Design of multi-modal antenna arrays for microwave hyperthermia and 1H/1⁹F MRI monitoring of drug release.

This simulation-based study presented a novel hybrid RF antenna array designed for neck cancer treatment within a 7T MRI system. The proposed design aimed to provide microwave hyperthermia to release 19F-labeled anticancer drugs from thermosensitive liposomes, facilitating drug concentration monitoring through 19F imaging and enabling 1H anatomical imaging and MR thermometry for temperature control. The design featured a bidirectional microstrip for generating the magnetic |B1|-fields required for 1H and 19F MR imaging, along with a patch antenna for localized RF heating. The bidirectional microstrip was operated at 300 MHz and 280 MHz through the placement of excitation ports at the ends of the antenna and an asymmetric structure along the antenna. Additionally, a patch antenna was positioned at the center. Based on this setup, an array of six antennas was designed. Simulation results using a tissue-mimicking simulation model confirmed the intensity and uniformity of |B1|-fields for both 19F and 1H nuclei, demonstrating the suitability of the design for clinical imaging. RF heating from the patch antennas was effectively localized at the center of the cancer model. In simulations with a human model, average |B1|-fields were 0.21 μT for 19F and 0.12 μT for 1H, with normalized-absolute-average-deviation values of 81.75% and 87.74%, respectively. Hyperthermia treatment was applied at 120 W for 600 s, achieving an average temperature of 40.22°C in the cancer model with a perfusion rate of 1 ml/min/kg. This study demonstrated the potential of a hybrid antenna array for integrating 1H MR, 19F drug monitoring, and hyperthermia.

Self-Isolated Dual-Mode High-Pass Birdcage RF Coil for Proton and Sodium MR Imaging at 7 T MRI

This study presents the feasibility of a dual-mode high-pass birdcage RF coil to acquire MR images at both 1H and 23Na frequencies at ultra-high-field MR scanner, 7 T. A dual-mode circuit (DMC) in the dual-mode birdcage (DMBC) RF coil operates at two frequencies, addressing the limitations of sensitivity reduction and isolation between two frequencies as in traditional dual-tuned RF coil. Finite-difference time-domain (FDTD) based electromagnetic (EM) simulations were performed to verify the RF coil at each frequency on the three-dimensional human head model. The DMBC RF coil resonated at proton (1H) and sodium (23Na) frequencies, and also single-tuned high-pass birdcage RF coils were constructed for both 1H and 23Na frequencies. The bench test performance of the RF coils was evaluated using network analysis parameters, including the measurement of scattering parameters (S-parameters) and quality factors (Q-factors). Q-factor of the DMBC coil at 1H port was 10.2% lower than that of 1H single-tuned birdcage (STBC) coil, with a modest SNR reduction of 6.5%. Similarly, the Q-factor for the DMBC coil at 23Na port was 12.3% less than that of 23Na STBC coil, and the SNR showed a minimal reduction of 5.4%. Utilizing the DMBC coil, promising 1H and 23Na MR images were acquired compared to those by using STBC coils. In conclusion, deploying a DMBC 1H/23Na coil has been demonstrated to overcome traditional constraints associated with dual-tuned RF coils, achieving this with only nominal signal attenuation across both nuclei operational frequencies.

#4196 MAGNETIC RESONANCE IMAGING ASSESSMENT OF SKIN AND MUSCLE SODIUM IN HAEMODIALYSIS

Abstract Background and Aims Haemodialysis (HD) is life sustaining for patients with end-stage kidney disease (ESKD) but is associated with a marked increase in incidence of cardiovascular disease (CVD) and high annual mortality rates. Sodium balance is regulated by the kidneys in health but has to be achieved by sodium removal during HD for those with ESKD. Recent evidence suggests that non-osmotically stored sodium in the muscle and/or skin may be a critical factor impacting the development of hypertension and CVD. Sodium magnetic resonance imaging (23Na MRI) allows assessment of skin and muscle sodium storage and may provide a valuable tool in evaluating sodium storage in dialysis patients. In this study, we used 23Na MRI to measure muscle and skin sodium content in younger and older healthy individuals and people receiving HD, and investigated the effect of a single dialysis session on muscle and skin sodium content. Method 23Na MRI was acquired on a 3T Philips Ingenia scanner using a custom-made 23Na RF coil. 3D GRE 23Na scans (3 × 3 × 30mm3, 10 slices) were acquired in a 15-minute scan. Four reference bottles of increasing sodium concentration were placed in the RF coil above the leg to calibrate sodium concentration. In the same imaging session, 1H MR images were acquired to delineate muscle groups, skin structures and tissue water content. 23Na concentration maps were generated using custom software and regions of interest of each muscle and the skin were manually segmented. Data was collected on 14 younger (23-38yrs,7M:7F) and three older (66-77yrs,3M:1F) healthy volunteers (HVs), and 5 male HD patients (55-68 yrs) who had been on HD for more than 3-months. HD patients underwent a pre-dialysis 23Na MRI calf scan, then had their usual dialysis session with a dialysate Na prescription of 137 mmol/L, followed by a repeat 23Na MRI calf scan post dialysis. Patient demographics, dialysis vintage, residual renal function, and ultrafiltration volume were collected, along with blood samples at the start and end of the dialysis session, including serum sodium. Results Figure 1 shows 23Na images in the younger and older HV group and HD patients pre-dialysis. Muscle and skin sodium was increased in older HVs compared to younger, with HD patients pre-dialysis tending to be lower than older HVs (Fig. 2). HD patients’ demographics and clinical measures pre- and post-dialysis are shown in Table 1. HD treatment reduced muscle sodium whilst skin sodium showed little change (Fig. 3). Conclusion We have optimised methods for measuring muscle and skin sodium. 23Na concentration in muscle and skin is higher in older subjects. HD patients’ 23Na values fall between those observed in the older and younger HV groups. These values are consistent with published data from patients dialysed against 137mmol/l sodium dialysate, but lower than other studies in which dialysate sodium levels were higher. Further studies are planned to study the effect of dialysate sodium on skin and muscle sodium concentrations and mechanistic links to cardiovascular disease.

Development of a Proton-Frequency-Transparent Birdcage Radiofrequency Coil for In Vivo 13C MRS/MRSI Study in a 3.0 T MRI System

A proton-frequency-transparent (PFT) birdcage RF coil that contains carbon-proton switching circuits (CPSCs) is presented to acquire 13C MR signals, which, in turn, enable 1H imaging with existing 1H RF coils without being affected by a transparent 13C birdcage RF coil. CPSCs were installed in the PFT 13C birdcage RF coil to cut the RF coil circuits during 1H MR imaging. Finite-difference time-domain (FDTD) electromagnetic (EM) simulations were performed to verify the performance of the proposed CPSCs. The performance of the PFT 13C birdcage RF coil with CPSCs was verified via phantom and in vivo MR studies. In the phantom MR studies, 1H MR images and 13C MR spectra were acquired and compared with each other using the 13C birdcage RF coil with and without the CPSCs. For the in vivo MR studies, hyperpolarized 13C cardiac MRS and MRSI of swine were performed. The proposed PFT 13C birdcage RF coil with CPSCs led to a percent image uniformity (PIU) reduction of 1.53% in the proton MR images when compared with the case without it. FDTD EM simulations revealed PIU reduction of 0.06% under the same conditions as the phantom MR studies. Furthermore, an SNR reduction of 5.5% was observed at 13C MR spectra of corn-oil phantom using the PFT 13C birdcage RF coil with CPSCs compared with that of the 13C birdcage RF coil without CPSCs. Utilizing the PFT 13C birdcage RF coil, 13C-enriched compounds were successfully acquired via in vivo hyperpolarized 13C MRS/MRSI experiments. In conclusion, the applicability and utility of the proposed 16-leg low-pass PFT 13C birdcage RF coil with CPSCs were verified via 1H MR imaging and hyperpolarized 13C MRS/MRSI studies using a 3.0 T MRI system.

Quantification of H217O by 1H-MR imaging at 3 T: a feasibility study

BackgroundIndirect 1H-magnetic resonance (MR) imaging of 17O-labelled water allows imaging in vivo dynamic changes in water compartmentalisation. Our aim was to describe the feasibility of indirect 1H-MR methods to evaluate the effect of H217O on the MR relaxation rates by using conventional a 3-T equipment and voxel-wise relaxation rates.MethodsMR images were used to calculate the R1, R2, and R2* relaxation rates in phantoms (19 vials with different H217O concentrations, ranging from 0.039 to 5.5%). Afterwards, an experimental animal pilot study (8 rats) was designed to evaluate the in vivo relative R2 brain dynamic changes related to the intravenous administration of 17O-labelled water in rats.ResultsThere were no significant changes on the R1 and R2* values from phantoms. The R2 obtained with the turbo spin-echo T2-weighted sequence with 20-ms echo time interval had the higher statistical difference (0.67 s−1, interquartile range 0.34, p < 0.001) and Spearman correlation (rho 0.79). The R2 increase was adjusted to a linear fit between 0.25 and 5.5%, represented with equation R2 = 0.405 concentration + 0.3215. The highest significant differences were obtained for the higher concentrations (3.1–5.5%). The rat brain MR experiment showed a mean 10% change in the R2 value after the H217O injection with progressive normalisation.ConclusionsIndirect 1H-MR imaging method is able to measure H217O concentration by using R2 values and conventional 3-T MR equipment. Normalised R2 relative dynamic changes after the intravenous injection of a H217O saline solution provide a unique opportunity to map water pathophysiology in vivo, opening the analysis of aquaporins status and modifications by disease at clinically available 3-T proton MR scanners.

OTME-13. Integration of metabolic and transcriptional signatures of glioblastoma invasion reveals extracellular matrix reorganization and vasculature remodeling

BackgroundThe invasive behavior of glioblastoma is considered highly relevant for recurrence. However, the invasion zone is difficult to visualize, typically lies outside the resected and irradiated area, and is protected by the blood brain barrier, posing a particular challenge for treatment. We present biological features of invasive growth accompanying tumor progression and invasion based on associated metabolic and transcriptomic changes in patient derived orthotopic xenografts (PDOX) and corresponding patients.MethodsPatients with suspected glioblastoma were enrolled (NCT02904525) and underwent 1H-MR spectroscopy and imaging (1H-MRS/I, 7T). Tissue obtained at surgery was transplanted orthotopically into immune-compromised mice. Longitudinal follow-up was performed by 1H-MRS/I (14.1T) on the injected and the contralateral side. The PDOX, the corresponding contralateral side, and the original human tumors underwent RNA-sequencing.ResultsThe temporal changes of the metabolite profiles characterized the kinetics of invasive growth of PDOX, and were patient specific. Comparison of 1H-MRS derived metabolite signatures, reflecting temporal changes of tumor development and invasion in PDOX, revealed high similarity to spatial metabolite signatures of combined multi-voxel analyses of the patients’ tumors. Associations between the metabolite profiles and the combined transcriptome of the xenografts and the host, reflected molecular signatures of invasion, comprising extracellular matrix degradation and reorganization, growth factor binding, and vascular remodeling.ConclusionIntegrating metabolic profiles and gene expression of highly invasive PDOX allows in vivo monitoring of progression in the non-enhancing tumor infiltration zone and provides insights into the remodeling of the extracellular matrix that is essential for cell-cell communication and regulation of cellular processes. The changes of the structural and biochemical properties of the extracellular matrix are of importance for the biological behavior of the tumors and may be subjected to therapeutic targeting.

Furin‐Controlled Fe3O4 Nanoparticle Aggregation and 19F Signal “Turn‐On” for Precise MR Imaging of Tumors

AbstractFor cancer diagnosis, 1H magnetic resonance imaging (MRI) is advantageous in sensitivity but lacks selectivity. Endogenous 19F MRI signal in humans is barely detectable and thus 19F MRI has very high selectivity. A combination of 1H and 19F MRI is ideal for precise tumor imaging but a protease‐controlled strategy of simultaneous T2 1H MRI enhancement and 19F MRI “Turn‐On” has not been reported. Here, used is a click condensation reaction to rationally project a dual‐functional fluorine probe 4‐(trifluoromethyl)benzoic acid (TFMB)‐Arg‐Val‐Arg‐Arg‐Cys(StBu)‐Lys‐CBT (1), which is further utilized to functionalize Fe3O4 nanoparticle (IONP) to achieve IONP@1. As such, the IONP aggregation can be activated by furin addition, thereby enhancing the T2 1H MRI signal and switching the 19F NMR/MRI signal “On”. Using this strategy, IONP@1 is successfully applied to detect the activity of the furin enzyme with “Turn‐On” 19F NMR/MRI and T2 1H MRI signals are enhanced. Moreover, IONP@1 is also applied for precise dual‐mode (1H and 19F) MR imaging of tumors in zebrafish under 14.1 T. The current approach, therefore, provides a feasible and robust means to reconcile the dilemma between selectivity and sensitivity of conventional MRI probes. More importantly, it is envisioned that, by substituting the TFMB moiety in 1 with a perfluorinated compound, this “smart” method could be of potential use for precise 1H MR and 19F MR imaging of tumor in mouse or in bigger rodents in near future.

Application of Magnetic Resonance to Assess Lyophilized Drug Product Reconstitution

PurposeDynamic in-situ proton (1H) magnetic resonance imaging (MRI) and 1H T2-relaxometry experiments are described in an attempt to: (i) understand the physical processes, that occur during the reconstitution of lyophilized bovine serum albumin (BSA) and monoclonal antibody (mAb) proteins; and (ii) objectify the reconstitution time.MethodsRapid two-dimensional 1H MRI and diffusion weighted MRI were used to study the temporal changes in solids dissolution and characterise water mass transport characteristics. One-shot T2 relaxation time measurements were also acquired in an attempt to quantify the reconstitution time. Both MRI data and T2-relaxation data were compared to standard visual observations currently adopted by industry. The 1H images were further referenced to MRI calibration data to give quantitative values of protein concentration and, percentage of remaining undissolved solids.ResultsAn algorithmic analysis of the 1H T2-relaxation data shows it is possible to classify the reconstitution event into three regimes (undissolved, transitional and dissolved). Moreover, a combined analysis of the 2D 1H MRI and 1H T2-relaxation data gives a unique time point that characterises the onset of a reconstituted protein solution within well-defined error bars. These values compared favourably with those from visual observations. Diffusion weighted MRI showed that low concentration BSA and mAb samples showed distinct liquid-liquid phase separation attributed to two liquid layers with significant density differences.ConclusionsT2 relaxation time distributions (whose interpretation is validated from the 2D 1H MR images) provides a quick and effective framework to build objective, quantitative descriptors of the reconstitution process that facilitate the interpretation of subjective visual observations currently adopted as the standard practice industry.

Selective Single-Site Pd-In Hydrogenation Catalyst for Production of Enhanced Magnetic Resonance Signals using Parahydrogen.

Pd-In/Al2 O3 single-site catalyst was able to show high selectivity (up to 98 %) in the gas phase semihydrogenation of propyne. Formation of intermetallic Pd-In compound was studied by XPS during reduction of the catalyst. FTIR-CO spectroscopy confirmed single-site nature of the intermetallic Pd-In phase reduced at high temperature. Utilization of Pd-In/Al2 O3 in semihydrogenation of propyne with parahydrogen allowed to produce ≈3400-fold NMR signal enhancement for reaction product propene (polarization=9.3 %), demonstrating the large contribution of pairwise hydrogen addition route. Significant signal enhancement as well as the high catalytic activity of the Pd-In catalyst allowed to acquire 1 H MR images of flowing hyperpolarized propene gas selectively for protons in CH, CH2 and CH3 groups. This observation is unique and can be easily transferred to the development of a useful MRI technique for an in situ investigation of selective semihydrogenation in catalytic reactors.

Local Intratracheal Delivery of Perfluorocarbon Nanoparticles to Lung Cancer Demonstrated with Magnetic Resonance Multimodal Imaging.

Eighty percent of lung cancers originate as subtle premalignant changes in the airway mucosal epithelial layer of bronchi and alveoli, which evolve and penetrate deeper into the parenchyma. Liquid-ventilation, with perfluorocarbons (PFC) was first demonstrated in rodents in 1966 then subsequently applied as lipid-encapsulated PFC emulsions to improve pulmonary function in neonatal infants suffering with respiratory distress syndrome in 1996. Subsequently, PFC nanoparticles (NP) were extensively studied as intravenous (IV) vascular-constrained nanotechnologies for diagnostic imaging and targeted drug delivery applications.Methods: This proof-of-concept study compared intratumoral localization of fluorescent paramagnetic (M) PFC NP in the Vx2 rabbit model using proton (1H) and fluorine (19F) magnetic resonance (MR) imaging (3T) following intratracheal (IT) or IV administration. MRI results were corroborated by fluorescence microscopy.Results: Dynamic 1H-MR and 19F-MR images (3T) obtained over 72 h demonstrated marked and progressive accumulation of M-PFC NP within primary lung Vx2 tumors during the first 12 h post IT administration. Marked 1H and 19F MR signal persisted for over 72 h. In contradistinction, IV M-PFC NP produced a modest transient signal during the initial 2 h post-injection that was consistent circumferential blood pool tumor enhancement. Fluorescence microscopy of excised tumors corroborated the MR results and revealed enormous intratumor NP deposition on day 3 after IT but not IV treatment. Rhodamine-phospholipid incorporated into the PFC nanoparticle surfactant was distributed widely within the tumor on day 3, which is consistent with a hemifusion-based contact drug delivery mechanism previously reported. Fluorescence microscopy also revealed similar high concentrations of M-PFC NP given IT for metastatic Vx2 lung tumors. Biodistribution studies in mice revealed that M-PFC NP given IV distributed into the reticuloendothelial organs, whereas, the same dosage given IT was basically not detected beyond the lung itself. PFC NP given IT did not impact rabbit behavior or impair respiratory function. PFC NP effects on cells in culture were negligible and when given IV or IT no changes in rabbit hematology nor serum clinical chemistry parameters were measured.Conclusion: IT delivery of PFC NP offered unique opportunity to locally deliver PFC NP in high concentrations into lung cancers with minimal extratumor systemic exposure.

Abstract 4335: The role of fibroblasts in prostate cancer cell invasion in tumor microenvironments

Abstract Cancer-associated fibroblasts (CAFs) play a critical role in tumor aggressiveness. We have started to investigate the role of CAFs in different tumor microenvironments of hypoxia and acidic extracellular pH. To further understand interactions between CAFs and cancer cells under carefully controlled conditions of hypoxia and acidic pH, we have used our MR compatible cell perfusion system to determine, for the first time, changes in the ability of prostate cancer cells to invade and degrade the extracellular matrix (ECM) in the presence of prostate myofibroblasts. Experiments were performed using the human prostate cancer cell lines PC-3 and prostate myofibroblasts (WPMY-1, ATCC, Manassas, VA). Before each MR experiment, 2.5X106 PC-3 cells were seeded on 0.5 ml of Plastic Plus beads in five 100mm dishes and grown for 4 days. Experiments were carried out with PC-3 cells plated on an ECM chamber with or without prostate myofibroblasts layered between the PC-3 and the ECM. For experiments investigating prostate myofibroblasts-cancer cell interaction, 5 X 104 prostate myofibroblasts were seeded on ECM gel contained in a chamber overnight before the MR experiment. This time interval allowed myofibroblasts to attach to the ECM gel. Degradation of ECM by cancer cells was determined at the 24h time point relative to the initial time point from the proton images. MR data were acquired on a 9.4 T MR spectrometer every 12 h over a period of 2 days. T1-weighted 1H MR imaging was performed to evaluate changes in ECM invasion and degradation. The extent of ECM degradation was estimated by drawing a region of interest (ROI) around the ECM gel region using NIH ImageJ software. The degradation index was defined as (ROIt=0-ROIt=24)/ROIt=0. One-dimensional 1H MR profiles of intracellular water were acquired along the length (z-axis) of the sample by diffusion- weighted MRI. These profiles were used to derive an invasion index by quantifying the number of cells invading into the ECM. Fibroblasts alone marginally degraded the matrigel. PC-3 cells, being invasive cells also degraded the ECM. However, ECM degradation increased when prostate myofibroblasts were layered between the ECM and the PC-3 prostate cancer cells. Consistent with the degradation data, PC-3 cells showed a significant increase in the invasive index in the presence of myofibroblasts under normoxia. The enhanced invasion and degradation of ECM by PC-3 cells in the presence of myofibroblasts suggests that the interaction between myofibroblasts and PC-3 cells plays a role in prostate cancer invasion. Further studies with hypoxia and acidic pH microenvironment are currently ongoing. Citation Format: Tariq Shah, Flonne Wildes, Dmitri Artemov, Zaver M. Bhujwalla. The role of fibroblasts in prostate cancer cell invasion in tumor microenvironments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4335. doi:10.1158/1538-7445.AM2017-4335

Gas Phase UTE MRI of Propane and Propene.

Proton magnetic resonance imaging (1H MRI) of gases can potentially enable functional lung imaging to probe gas ventilation and other functions. Here, 1H MR images of hyperpolarized (HP) and thermally polarized propane gas were obtained using ultrashort echo time (UTE) pulse sequence. A 2-dimensional (2D) image of thermally polarized propane gas with ∼0.9 × 0.9 mm2 spatial resolution was obtained in <2 seconds, showing that even non-HP hydrocarbon gases can be successfully used for conventional proton magnetic resonance imaging. The experiments were also performed with HP propane gas, and high-resolution multislice FLASH 2D images in ∼510 seconds and non-slice-selective 2D UTE MRI images were acquired in ∼2 seconds. The UTE approach adopted in this study can be potentially used for medical lung imaging. Furthermore, the possibility of combining UTE with selective suppression of 1H signals from 1 of the 2 gases in a mixture is shown in this MRI study. The latter can be useful for visualizing industrially important processes where several gases may be present, eg, gas–solid catalytic reactions.

(1)H-MR imaging of the lungs at 3.0 T.

One disadvantage of magnetic resonance imaging (MRI) is the inability to adequately image the lungs. Recent advances in hyperpolarized gas technology [e.g., helium-3 ((3)He) and xenon-129 ((129)Xe)] have changed this. However, the required technology is expensive and often needing extra physics or engineering staff. Hence there is considerable interest in developing (1)H (proton)-based MRI approaches that can be readily implemented on standard clinical systems. Thus, the purpose of this work was to compare a newly developed free breathing proton-based MR lung imaging method to that of a standard gadolinium (Gd) based perfusion approach. Healthy volunteers [10] were scanned using a 3-T MRI with 8 parallel receivers, and a cardiac gated fast spin echo (FSE) sequence. Acquisition was cardiac triggered, with different time delays incremented to cover the entire cardiac cycle. Image k-space was filled rectilinearly. But to reduce motion artefacts k-space was retrospectively sorted using the minimal variance algorithm (MVA), based on physiologic data recorded from both the respiratory bellows and electrocardiogram (ECG). Resorted and reconstructed FSE images were compared to contrast enhanced lung images, obtained following intravenous injection of Gd-DTPA-BMA. Biphasic variation in FSE lung signal intensity was observed across the cardiac cycle with a maximal signal change following rapid cardiac ejection (between S and T waves), and following rapid isovolumetric relaxation. A difference image between systolic and diastolic states in the cardiac cycle resulted in images with improved lung contrast to noise ratio (CNR). FSE image intensity was uniform over lung parenchyma while Gd-based enhancement of spoiled gradient recalled echo (SPGR) images showed gravitational dependence. Here we show how 1H-MR images of lung can be obtained during free breathing. The image contrast obtained during this approach is likely the result of flow and oxygen modulation during the cardiac cycle. This free breathing method provides lung images comparable to those obtained using Gd-enhancement. Besides having the advantage of free breathing, this approach doesn't require any Gd-contrast or suffer from methodological problems associated with perfusion (e.g., poor bolus timing). However, as gravitational differences typically observed in lung perfusion are not visible with this method it is not providing exclusive microvascular perfusion information.

β-Hydroxybutyrate attenuates NMDA-induced spasms in rats with evidence of neuronal stabilization on MR spectroscopy

BackgroundInfantile spasms (IS) is a devastating epileptic encephalopathy. The ketogenic diet (KD) has been successfully used as a treatment for IS. This study was designed to test whether beta-hydroxybutyrate (BHB), a major metabolite of the KD, is effective in an animal model of IS. MethodsPregnant rats received betamethasone on gestational day 15. The offspring received either single [30min prior to NMDA-triggered spasms on postnatal day (P) 15] or prolonged (three per day from P12 to P15) i.p. BHB. An additional experiment used repeated bouts of spasms on P12, P13, and P15 with randomized prolonged BHB treatment initiated after the first spasms. We determined the latency to onset of spasms and the number of spasms after the NMDA injection on P15. The rats that received randomized BHB treatment were also monitored with open field, sociability, and fear-conditioning tests and underwent in vivo 1H MR imaging on a 9.4T MR system after NMDA-induced spasms. The acquired 1H MR spectra were quantified using LC model. ResultsSingle-dose BHB pretreatment had no effect on spasms. In contrast, prolonged pretreatment with BHB significantly delayed the onset and decreased the frequency of spasms. In addition, randomized prolonged BHB treatment resulted in a significant reduction in number of spasms at P15. BHB treatment had no significant effect on motor activities, but significantly decreased the interactions with strangers and increased the contextual memory. On MR spectroscopic analysis of randomized prolonged BHB-treated rats at 24h after the cluster of spasms, the elevation of GABA, glutamine, glutamate, total creatine, macromolecule-plus lipids, and N-acetylaspartate levels after spasms were significantly attenuated by randomized BHB treatment (p<0.05). SignificanceProlonged administration of BHB directly suppresses development of spasms in a rat model of IS with acute stabilization of brain metabolites. Additionally, BHB appears to decrease the interests to other rats and improve memory responses.

Using magnetic resonance imaging to study enzymatic hydrogelation.

Herein, we report, for the first time, the use of MRI methods to study enzymatic hydrogelation. Supramolecular hydrogels have been exploited as biomaterials for many applications. However, behaviors of the water molecules encapsulated in hydrogels have not been fully understood. In this work, we designed a precursor 1 which could self-assemble into nanofibers and form hydrogel I (gel I) upon the catalysis of phosphatase. The differences of mechanic property, pore size, water diffusion rate, and magnetic resonance relaxation times T1 and T2 of gel I containing different concentrations of 1 were systematically studied and analyzed. T1, T2, and diffusion-weighted (1)H MR images from gel I phantoms were obtained at 9.4 T. Analyses of the MRI data uncovered how the density of the nanofiber networks affects the relaxation behaviors of the water protons encapsulated in such hydrogels. Rheological analyses and cryo-TEM observations showed increased gel elasticities with increased concentrations of 1 while the pore sizes of gel I decreased. This also resulted in an increase in the proton relaxation rate (i.e., shortened T1, T2, and apparent diffusion coefficient (ADC)) for the water encapsulated in the hydrogel. With MRI, our study provides a new in vitro method to potentially mimic and study in vivo diseases that involve fibrous aggregates.

Injectable hyaluronic acid hydrogel for 19F magnetic resonance imaging

We report on a19F labeled injectable hyaluronic acid (HA) hydrogel that can be monitored by both 1H and 19F MR imaging. The HA based hydrogel formed via carbazone reaction can be obtained within a minute by simple mixing of HA-carbazate and HA-aldehyde derivatized polymers. 19F contrast agent was linked to with carbazate and thiol dually functionalized HA via orthogonal Michael addition reaction which afforded cross-linkable and 19F labeled HA. The 19F labeling of HA polymer did not affect the mechanical properties of the formed hydrogel. As a result, the shape of a hydrogel sample could be imaged very well by both 1H MRI and high resolution19F MRI. This hydrogel has high potential in clinical applications since it is injectable, biocompatible, and can be tracked in a minimally invasive manner. The present approach can be applied in preparation of injectable 19F labeled hydrogel biomaterials from other natural biomacromolecules.

S8 Hyperpolarised 3He MRI is superior to lung clearance index in detection of ventilation abnormalities in young children with mild CF

IntroductionHyperpolarised 3He MRI provides high resolution images of lung ventilation and is more sensitive than spirometry to early changes in lung ventilation in cystic fibrosis (CF). Lung clearance index (LCI)...

1H MRI study of small-diameter silk vascular grafts in water

Small-diameter vascular grafts (VG) made from silk fibroin (SF) fibers by a double-raschel knitting method were prepared by coating their interior and exterior with different materials, such as SF or polyurethane (PU). The 1H spin density, 1H spin–spin relaxation time (T2) and diffusion coefficient (D) of the water molecules in the layer of the VG coated by these materials were non-destructively observed in water using 1H NMR imaging. The inner and outer coating materials significantly affected the amount and mobility of water molecules in the VG. The water content of the SF-coated VG was considerably higher than that of PU-coated VG. The T2 value of the water molecules in the SF-coated VG layer was smaller than that of the PU-coated VG, which means that the rotational motion of the water molecules in the layer of the SF-coated VG was restricted by the intermolecular interaction between the SF and water molecules. The diffusion coefficient (D) of the water molecules in the SF-coated VG layer was larger than that of the PU-coated VG, indicating that the water molecules were confined to the pores in the graft layer of the PU-coated VG. The images of 1H spin density, 1H T2 and diffusion coefficient (D) of water molecules in the layer of silk-based vascular grafts (VG) coated by different materials that are silk fibroin or polyurethane were non-destructively observed in water using 1H MR imaging. The inner and outer coating materials affect significantly the amount and mobility of water molecules in the VG.

A volume birdcage coil with an adjustable sliding tuner ring for neuroimaging in high field vertical magnets: Ex and in vivo applications at 21.1 T

A tunable 900MHz transmit/receive volume coil was constructed for 1H MR imaging of biological samples in a 21.1T vertical bore magnet. To accommodate a diverse range of specimen and RF loads at such a high frequency, a sliding-ring adaptation of a low-pass birdcage was implemented through simultaneous alteration of distributed capacitance. To make efficient use of the constrained space inside the vertical bore, a modular probe design was implemented with a bottom-adjustable tuning and matching apparatus. The sliding ring coil displays good homogeneity and sufficient tuning range for different samples of various dimensions representing large span of RF loads. High resolution in vivo and ex vivo images of large rats (up to 350g), mice and human postmortem tissues were obtained to demonstrate coil functionality and to provide examples of potential applications at 21.1T.

In vivo cardiac 31P MRS in a mouse model of heart failure

ObjectiveTo investigate myocardial energy status in a mouse model of heart failure using in vivo 31P magnetic resonance spectroscopy (MRS).MethodsMale C57BL/6 mice underwent thoracic aortic constriction (TAC) surgery, inducing pressure‐overload cardiomyopathy, and were measured seven weeks after surgery (n = 5). Healthy wild‐type mice served as controls (n = 4). Cardiac cine 1H MR images were made for reference purposes and to quantify left ventricular (LV) function. Cardiac 31P MR spectra were measured from a ~6 mm cubic voxel enclosing the end‐diastolic LV myocardium using ECG triggered, respiratory gated 3D Image‐Selected In vivo Spectroscopy (ISIS).ResultsLV end‐diastolic volume and LV mass normalized to body weight were higher in TAC mice compared to controls (91.7 ± 19.0 versus 61.8 ± 6.0 μL and 4.4 ± 0.6 versus 3.1 ± 0.2 mg/g, P &lt; 0.01), whereas LV ejection fraction was reduced in TAC mice (45.4 ± 20.0 versus 64.4 ± 5.2 %, P &lt; 0.05). Myocardial phosphocreatine‐to‐ATP ratio was lower in TAC mice when compared to healthy controls (0.8±0.2 versus 1.2±0.2, P &lt; 0.05).ConclusionDecreased EF in TAC mice is accompanied by decreased phosphocreatine‐to‐ATP ratio, indicating a disturbed energy homeostasis in this mouse model of heart failure. This research was funded by a VIDI grant from the Netherlands Organisation for Scientific Research (NWO).