A continuous flow bioreactor system for high-throughput hyperpolarized metabolic flux analysis.

Hyperpolarized carbon-13 labeled compounds are increasingly being used in medical MR imaging (MRI) and MR imaging (MRI) and spectroscopy (MRS) research, due to its ability to monitor tissue and cell metabolism in real-time. Although radiological biomarkers are increasingly being considered as clinical indicators, biopsies are still considered the gold standard for a large variety of indications. Bioreactor systems can play an important role in biopsy examinations because of their ability to provide a physiochemical environment that is conducive for therapeutic response monitoring ex vivo. We demonstrate here a proof-of-concept bioreactor and microcoil receive array setup that allows for ex vivo preservation and metabolic NMR spectroscopy on up to three biopsy samples simultaneously, creating an easy-to-use and robust way to simultaneously run multisample carbon-13 hyperpolarization experiments. Experiments using hyperpolarized [1-13C]pyruvate on ML-1 leukemic cells in the bioreactor setup were performed and the kinetic pyruvate-to-lactate rate constants ( k PL ) extracted. The coefficient of variation of the experimentally found k PL s for five repeated experiments was C V = 35 % . With this statistical power, treatment effects of 30%-40% change in lactate production could be easily differentiable with only a few hyperpolarization dissolutions on this setup. Furthermore, longitudinal experiments showed preservation of ML-1 cells in the bioreactor setup for at least 6 h. Rat brain tissue slices were also seen to be preserved within the bioreactor for at least 1 h. This validation serves as the basis for further optimization and upscaling of the setup, which undoubtedly has huge potential in high-throughput studies with various biomarkers and tissue types.

Trade-off between preamplifier noise figure and decoupling in MRI detectors.

PURPOSE: There is a limit to the maximum achievable preamplifier decoupling. In many cases, this level is not enough. To overcome this limit, the preamplifier noise figure can be compromised for further decoupling increase. This is useful in flexible MRI arrays where ensuring coil insensitivity to changes in other array elements is a challenge. METHODS: This work establishes the relation between the preamplifier noise figure and preamplifier decoupling using closed-form equations. These equations allow the evaluation of preamplifier decoupling properties and benchmark different preamplifiers against each other. The method to design the corresponding decoupling networks is described. The derived generalized design equations, which are not limited to 50 Ω pre-matched preamplifiers, greatly improve design flexibility and enable use of new amplifiers in MRI detectors. RESULTS: Using the method, the decoupling properties of three preamplifiers are studied. For demonstration, the coil decoupling is further increased by 10.8 dB using one of the preamplifiers. The noise figure is sacrificed by 0.5 dB, which is predicted by equations and verified experimentally. Although examples are shown for 3 T systems at 32.13 MHz and 127.7 MHz, the approach and equations apply to any field strength and nucleus. CONCLUSION: Preamplifier decoupling can be improved beyond what is possible by traditional approaches. The derived design equations cover a wide range of cases, including inductive coils and self-resonant low-impedance and high-impedance coils.

A cryogenic 14-channel 13 C receiver array for 3T human head imaging.

PURPOSE: This article presents a novel 14-channel receive-only array for 13 C human head imaging at 3 T that explores the SNR gain by operating at cryogenic temperature cooled by liquid nitrogen. METHODS: Cryostats are developed to evaluate single-coil bench SNR performance and cool the 14-channel array with liquid nitrogen while having enough thermal insulation between the coils and the sample. The temperature distribution for the coil array is measured. Circuits are adapted to the -189°C environment and implemented in the 14-channel array. 13 C images are acquired with the array at cryogenic and room temperature in a 3T scanner. RESULTS: Compared with room temperature, the array at cryogenic temperature provides 27%-168% SNR improvement over all voxels and 47% SNR improvement near the image center. The measurements show a decrease of the element noise correlation at cryogenic temperature. CONCLUSION: It is demonstrated that higher SNR can be achieved by cryogenically cooling the 14-channel array. A cryogenic array suitable for clinical imaging can be further developed on the array proposed. The cryogenic coil array is most likely suited for scenarios in which high SNR deep in a head and decent SNR on the periphery are required.

Development of Dissolution Dynamic Nuclear Polarization of [15 N3 ]Metronidazole: A Clinically Approved Antibiotic.

We report dissolution Dynamic Nuclear Polarization (d-DNP) of [15 N3 ]metronidazole ([15 N3 ]MNZ) for the first time. Metronidazole is a clinically approved antibiotic, which can be potentially employed as a hypoxia-sensing molecular probe using 15 N hyperpolarized (HP) nucleus. The DNP process is very efficient for [15 N3 ]MNZ with an exponential build-up constant of 13.8 min using trityl radical. After dissolution and sample transfer to a nearby 4.7 T Magnetic Resonance Imaging scanner, HP [15 N3 ]MNZ lasted remarkably long with T1 values up to 343 s and 15 N polarizations up to 6.4 %. A time series of HP [15 N3 ]MNZ images was acquired in vitro using a steady state free precession sequence on the 15 NO2 peak. The signal lasted over 13 min with notably long T2 of 20.5 s. HP [15 N3 ]MNZ was injected in the tail vein of a healthy rat, and dynamic spectroscopy was performed over the rat brain. The in vivo HP 15 N signals persisted over 70 s, demonstrating an unprecedented opportunity for in vivo studies.

RF coil design for accurate parallel imaging on 13 C MRSI using 23 Na sensitivity profiles.

PURPOSE: To develop a coil-based method to obtain accurate sensitivity profiles in 13 C MRI at 3T from the endogenous 23 Na. An eight-channel array is designed for 13 C MR acquisitions. As application examples, the array is used for two-fold accelerated acquisitions of both hyperpolarized 13 C metabolic imaging of pig kidneys and the human brain. METHODS: A flexible coil array was tuned optimally for 13 C at 3T (32.1 MHz), with the coil coupling coefficients matched to be nearly identical at the resonance frequency of 23 Na (33.8 MHz). This is done by enforcing a high decoupling (obtained through highly mismatched preamplifiers) and adjusting the coupling frequency response. The SNR performance is compared to reference coils. RESULTS: The measured sensitivity profiles on a phantom showed high spatial similarity for 13 C and 23 Na resonances, with average noise correlation of 9 and 11%, respectively. For acceleration factors 2, 3, and 4, the obtained maximum g-factors were 1.0, 1.1, and 2.6, respectively. The 23 Na profiles obtained in vivo could be used successfully to perform two-fold acceleration of hyperpolarized 13 C 3D acquisitions of both pig kidneys and a healthy human brain. CONCLUSION: A receive array has been developed in such a way that the 13 C sensitivity profiles could be accurately obtained from measurements at the 23 Na frequency. This technique facilitates accelerated acquisitions for hyperpolarized 13 C imaging. The SNR performance obtained at the 13 C frequency, compares well to other state-of-the-art coils for the same purpose, showing slightly better superficial and central SNR.

Metabolism of hyperpolarised [1-13 C]pyruvate in awake and anaesthetised rat brains.

The use of hyperpolarised 13 C pyruvate for nononcological neurological applications has not been widespread so far, possibly due to delivery issues limiting the visibility of metabolites. First proof-of-concept results have indicated that metabolism can be detected in human brain, and this may supersede the results obtained in preclinical settings. One major difference between the experimental setups is that preclinical MRI/MRS routinely uses anaesthesia, which alters both haemodynamics and metabolism. Here, we used hyperpolarised [1-13 C]pyruvate to compare brain metabolism in awake rats and under isoflurane, urethane or medetomidine anaesthesia. Spectroscopic [1-13 C]pyruvate time courses measured sequentially showed that pyruvate-to-bicarbonate and pyruvate-to-lactate labelling rates were lower in isoflurane animals than awake animals. An increased bicarbonate-to-lactate ratio was observed in the medetomidine group compared with other groups. The study shows that hyperpolarised [1-13 C]pyruvate experiments can be performed in awake rats, thus avoiding anaesthesia-related issues. The results suggest that haemodynamics probably dominate the observed pyruvate-to-metabolite labelling rates and area-under-time course ratios of referenced to pyruvate. On the other hand, the results obtained with medetomidine suggest that the ratios are also modulated by the underlying cerebral metabolism. However, the ratios between intracellular metabolites were unchanged in awake compared with isoflurane-anaesthetised rats.

Three-element matching networks for receive-only MRI coil decoupling.

PURPOSE: Preamplifier decoupling is useful for minimizing interaction between MRI array elements. The purpose of this work is to propose a general approach to designing networks for preamplifier decoupling while keeping the number of elements to a minimum. The approach is applicable to arbitrary impedance preamplifiers and arbitrary coil impedances. METHODS: Closed form design equations for decoupling networks are derived based on maximum decoupling and minimum preamplifier noise conditions. The analytical solutions are verified using numerical simulations. Design examples at 32.1, 64, 128, and 298 MHz are shown. One of the examples is realized on a test bench. The fabricated circuit is tested for decoupling and minimum noise properties. RESULTS: The design equations are verified numerically and experimentally. The fabricated network demonstrates 30.7 dB of decoupling and minimum output noise at the design frequency. CONCLUSION: The design equations lead to four alternative network solutions. Each network is realized as a T-shape or Π-shape three elements circuit topology. All four networks are identical in performance providing minimum amplifier noise and maximum decoupling for a given preamplifier and coil combination. An MRI array designer can choose any solution out of four. The considerations for choosing the most practical solution are given. The presented method enables the use of arbitrary impedance preamplifiers or transistors (not necessary 50 Ω) and provides the most compact design possible (with the least number of components), which is particularly useful in multi-element systems.

[68Ga]Ga-NODAGA-E[(cRGDyK)]2 PET and hyperpolarized [1-13C] pyruvate MRSI (hyperPET) in canine cancer patients: simultaneous imaging of angiogenesis and the Warburg effect.

PURPOSE: Cancer has a multitude of phenotypic expressions and identifying these are important for correct diagnosis and treatment selection. Clinical molecular imaging such as positron emission tomography can access several of these hallmarks of cancer non-invasively. Recently, hyperpolarized magnetic resonance spectroscopy with [1-13C] pyruvate has shown great potential to probe metabolic pathways. Here, we investigate simultaneous dual modality clinical molecular imaging of angiogenesis and deregulated energy metabolism in canine cancer patients. METHODS: Canine cancer patients (n = 11) underwent simultaneous [68Ga]Ga-NODAGA-E[(cRGDyK)]2 (RGD) PET and hyperpolarized [1-13C]pyruvate-MRSI (hyperPET). Standardized uptake values and [1-13C]lactate to total 13C ratio were quantified and compared generally and voxel-wise. RESULTS: Ten out of 11 patients showed clear tumor uptake of [68Ga]Ga-NODAGA-RGD at both 20 and 60 min after injection, with an average SUVmean of 1.36 ± 0.23 g/mL and 1.13 ± 0.21 g/mL, respectively. A similar pattern was seen for SUVmax values, which were 2.74 ± 0.41 g/mL and 2.37 ± 0.45 g/mL. The [1-13C]lactate generation followed patterns previously reported. We found no obvious pattern or consistent correlation between the two modalities. Voxel-wise tumor values of RGD uptake and lactate generation analysis revealed a tendency for each canine cancer patient to cluster in separated groups. CONCLUSION: We demonstrated combined imaging of [68Ga]Ga-NODAGA-RGD-PET for angiogenesis and hyperpolarized [1-13C]pyruvate-MRSI for probing energy metabolism. The results suggest that [68Ga]Ga-NODAGA-RGD-PET and [1-13C]pyruvate-MRSI may provide complementary information, indicating that hyperPET imaging of angiogenesis and energy metabolism is able to aid in cancer phenotyping, leading to improved therapy planning.

Hyperpolarization via dissolution dynamic nuclear polarization: new technological and methodological advances.

Dissolution-DNP is a method to boost liquid-state NMR sensitivity by several orders of magnitude. The technique consists in hyperpolarizing samples by solid-state dynamic nuclear polarization at low temperature and moderate magnetic field, followed by an instantaneous melting and dilution of the sample happening inside the polarizer. Although the technique is well established and the outstanding signal enhancement paved the way towards many applications precluded to conventional NMR, the race to develop new methods allowing higher throughput, faster and higher polarization, and longer exploitation of the signal is still vivid. In this work, we review the most recent advances on dissolution-DNP methods trying to overcome the original technique's shortcomings. The review describes some of the new approaches in the field, first, in terms of sample formulation and properties, and second, in terms of instrumentation.

Unexpected Anomeric Acceptor Preference Observed Using dDNP NMR for Transglycosylation Studies of ß-Galactosidases.

The transglycosylation abilities of ß-galactosidases were investigated using hyperpolarized [U-13C,U-2H]glucose as an acceptor and o-nitrophenyl ß-galactopyranoside as a donor. Several products were readily observable, and at least in the case when O3 acted as an acceptor, the enzymes showed a clear selectivity toward the ß-anomer of glucose. Additionally, it was possible to determine the relative hydrolysis rates of the formed transglycosylation products, providing information on the selectivity as well. Using this method, the transglycosylation abilities of the enzymes could be studied at a very high temporal resolution as well as with high sensitivity, and due to the relative ease of the setup, this method could be more generally applied to investigate glycosidases.

Autonomous cryogenic RF receive coil for 13 C imaging of rodents at 3 T.

PURPOSE: To develop an autonomous, in-bore, MR-compatible cryostat cooled with liquid nitrogen that provides full-day operation, and to demonstrate that the theoretical signal-to-noise benefit can be achieved for 13 C imaging at 3 T (32.13 MHz). METHODS: The cryogenic setup uses a vacuum-insulated fiberglass cryostat, which indirectly cools a cold finger where the RF coil is attached. The cryostat was evacuated before use and had a reservoir of liquid nitrogen for full-day operation. A 30 × 40 mm2 copper coil was mounted inside the cryostat with a 3-mm distance to the sample. Two examples of in vivo experiments of rat brain metabolism after a hyperpolarized [1-13 C]pyruvate injection are reported. RESULTS: A coil Q-factor ratio of Q88K /Q290K = 550/280 was obtained, and the theoretical SNR enhancement was verified with MR measurements. We achieved a coil temperature of 88 K and a preamplifier temperature of 77 K. A 2-fold overall SNR enhancement was achieved, compared with the best case at room temperature. The thermal performance of the coil was adequate for in vivo experiments, with an autonomy of 5 hours consuming 6 L of LN2 , extendable to over 12 hours by LN2 refilling. CONCLUSION: Cryogenic surface coils can be highly beneficial for 13 C imaging, provided that the coil-to-sample distance remains short. An autonomous, in-bore cryostat was developed that achieved the theoretical improvement in SNR.

Three-dimensional accelerated acquisition for hyperpolarized 13 C MR with blipped stack-of-spirals and conjugate-gradient SENSE.

PURPOSE: To test a new parallel imaging strategy for acceleration of hyperpolarized 13 C MR acquisitions based on a 3D blipped stack-of-spirals trajectory and conjugate-gradient SENSE reconstruction with precalibrated sensitivities. METHODS: The blipped stack-of-spirals trajectory was developed for an acceleration factor of 4, based on an undersampled stack-of-spirals with gradient blips during spiral readout. The trajectory was developed with volumetric coverage of a large FOV and with high spatial resolution. High temporal resolution was attained through spectral-spatial excitation and 4 excitations per volume. The blipped stack-of-spirals was evaluated in simulations and phantom experiments. Next, the method was evaluated for kidney and cardiac imaging in 2 separate healthy pigs. RESULTS: Simulation and phantom results showed successful acquisition and reconstruction, but also revealed reconstruction challenges for certain locations and for wide signal sources. For the kidney experiment, the accelerated acquisition showed high similarity to 2 separately acquired fully sampled data sets with matched spatial and temporal resolution, respectively. For the cardiac experiment, the accelerated acquisition proved able to map each metabolite in 3 dimensions within a single cardiac cycle. CONCLUSION: The proposed method demonstrated effective mapping of metabolism in both kidneys and the heart of healthy pigs. Limitations seen in phantom experiments, may be irrelevant for most clinical applications, but should be kept in mind as well as reconstruction challenges related to residual aliasing. All in all, we show that the blipped stack-of-spirals is a relevant parallel imaging method for hyperpolarized human imaging, facilitating better insights into metabolism compared with nonaccelerated acquisition.

Creating a clinical platform for carbon-13 studies using the sodium-23 and proton resonances.

PURPOSE: Calibration of hyperpolarized 13 C-MRI is limited by the low signal from endogenous carbon-containing molecules and consequently requires 13 C-enriched external phantoms. This study investigated the feasibility of using either 23 Na-MRI or 1 H-MRI to calibrate the 13 C excitation. METHODS: Commercial 13 C-coils were used to estimate the transmit gain and center frequency for 13 C and 23 Na resonances. Simulations of the transmit B1 profile of a Helmholtz loop were performed. Noise correlation was measured for both nuclei. A retrospective analysis of human data assessing the use of the 1 H resonance to predict [1-13 C]pyruvate center frequency was also performed. In vivo experiments were undertaken in the lower limbs of 6 pigs following injection of hyperpolarized 13 C-pyruvate. RESULTS: The difference in center frequencies and transmit gain between tissue 23 Na and [1-13 C]pyruvate was reproducible, with a mean scale factor of 1.05179 ± 0.00001 and 10.4 ± 0.2 dB, respectively. Utilizing the 1 H water peak, it was possible to retrospectively predict the 13 C-pyruvate center frequency with a standard deviation of only 11 Hz sufficient for spectral-spatial excitation-based studies. CONCLUSION: We demonstrate the feasibility of using the 23 Na and 1 H resonances to calibrate the 13 C transmit B1 using commercially available 13 C-coils. The method provides a simple approach for in vivo calibration and could improve clinical workflow.

Detection of lentiviral suicide gene therapy in C6 rat glioma using hyperpolarised [1-13 C]pyruvate.

Hyperpolarised [1-13 C]pyruvate MRI has shown promise in monitoring therapeutic efficacy in a number of cancers including glioma. In this study, we assessed the pyruvate response to the lentiviral suicide gene therapy of herpes simplex virus-1 thymidine kinase with the prodrug ganciclovir (HSV-TK/GCV) in C6 rat glioma and compared it with traditional MR therapy markers. Female Wistar rats were inoculated with 106 C6 glioma cells. Treated animals received intratumoural lentiviral HSV-TK gene transfers on days 7 and 8 followed by 2-week GCV therapy starting on day 10. Animals were repeatedly imaged during therapy using volumetric MRI, diffusion and relaxation mapping, as well as metabolic [1-13 C]pyruvate MRS imaging. Survival (measured as time before animals reached a humane endpoint and were euthanised) was assessed up to day 30 posttherapy. HSV-TK/GCV gene therapy lengthened the median survival time from 12 to 25 days. This was accompanied by an apparent tumour growth arrest, but no changes in diffusion or relaxation parameters in treated animals. The metabolic response was more evident in the case-by-case analysis than in the group-level analysis. Treated animals also showed a 37 ± 15% decrease (P < 0.05, n = 5) in lactate-to-pyruvate ratio between therapy weeks, whereas a 44 ± 18% increase (P < 0.05, n = 6) was observed in control animals. Hyperpolarised [1-13 C]pyruvate MRI can offer complementary metabolic information to traditional MR methods to give a more comprehensive picture of the slowly developing gene therapy response. This may benefit the detection of the successful therapy response in patients.

Dynamic 2D and 3D mapping of hyperpolarized pyruvate to lactate conversion in vivo with efficient multi-echo balanced steady-state free precession at 3 T.

The aim of this study was to acquire the transient MRI signal of hyperpolarized tracers and their metabolites efficiently, for which specialized imaging sequences are required. In this work, a multi-echo balanced steady-state free precession (me-bSSFP) sequence with Iterative Decomposition with Echo Asymmetry and Least squares estimation (IDEAL) reconstruction was implemented on a clinical 3 T positron-emission tomography/MRI system for fast 2D and 3D metabolic imaging. Simulations were conducted to obtain signal-efficient sequence protocols for the metabolic imaging of hyperpolarized biomolecules. The sequence was applied in vitro and in vivo for probing the enzymatic exchange of hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate. Chemical shift resolution was achieved using a least-square, iterative chemical species separation algorithm in the reconstruction. In vitro, metabolic conversion rate measurements from me-bSSFP were compared with NMR spectroscopy and free induction decay-chemical shift imaging (FID-CSI). In vivo, a rat MAT-B-III tumor model was imaged with me-bSSFP and FID-CSI. 2D metabolite maps of [1-13 C]pyruvate and [1-13 C]lactate acquired with me-bSSFP showed the same spatial distributions as FID-CSI. The pyruvate-lactate conversion kinetics measured with me-bSSFP and NMR corresponded well. Dynamic 2D metabolite mapping with me-bSSFP enabled the acquisition of up to 420 time frames (scan time: 180-350 ms/frame) before the hyperpolarized [1-13 C]pyruvate was relaxed below noise level. 3D metabolite mapping with a large field of view (180 × 180 × 48 mm3 ) and high spatial resolution (5.6 × 5.6 × 2 mm3 ) was conducted with me-bSSFP in a scan time of 8.2 seconds. It was concluded that Me-bSSFP improves the spatial and temporal resolution for metabolic imaging of hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate compared with either of the FID-CSI or EPSI methods reported at 3 T, providing new possibilities for clinical and preclinical applications.

Subjective recovery from pregnancy-related pelvic girdle pain the first 6 weeks after delivery: a prospective longitudinal cohort study.

PURPOSE: The purpose of this study was to investigate the subjective recovery from pregnancy-related pelvic girdle pain (PGP) during the first 6 weeks after delivery and to detect possible risk factors for a poor recovery. METHODS: The participants were included in this study at the routine ultrasound examination at 18 weeks of pregnancy. The women received a weekly SMS with the question "How many days during the last week has your PGP been bothersome?" The SMS-track from the final 10 weeks of pregnancy and first 6 weeks after delivery were assessed and sorted, based on individual graphs. A total of 130 women who reported PGP during pregnancy and met for clinical examination 6 weeks after delivery were included in the study. RESULTS: In all, 83% of the women experienced substantial recovery from severe or moderate PGP within 6 weeks after delivery. Of these, 44% reported a substantial recovery already within 2 weeks after delivery. More multiparous women, women reporting PGP the year before pregnancy, and women with high pain intensity during pregnancy had a poor recovery. CONCLUSIONS: The prognosis following PGP in pregnancy is good and the majority of women recovered substantially from severe and moderate pregnancy-related PGP within 6 weeks after delivery. For many women, a subjective substantial recovery occurred within 2 weeks after delivery. Predictors for a poor recovery were multiparity, PGP the year before pregnancy and a high pain intensity during pregnancy. These slides can be retrieved under Electronic Supplementary Material.

Identifying existential concerns as an analytical tool: an eye-opener for the doctor.

Existential concerns manifest themselves emotionally in patients. Emotions tend to be transferred between patient and doctor but the underlying existential concerns may remain hidden and obscure for both. If doctors understand that there are always existential concerns behind patients' inquiries it becomes easier to relate to the patient's feelings in an interested and curious way. Ultimately this benefits both doctors and patients. We have observed five existential human concerns leads to strong emotions (1. death, 2. thrown-ness, 3. aloneness, 4. choosing (the imperative of choice) and 5. meaninglessness (the absence of objective meaning).

DJ-1 is a redox sensitive adapter protein for high molecular weight complexes involved in regulation of catecholamine homeostasis.

DJ-1 is an oxidation sensitive protein encoded by the PARK7 gene. Mutations in PARK7 are a rare cause of familial recessive Parkinson's disease (PD), but growing evidence suggests involvement of DJ-1 in idiopathic PD. The key clinical features of PD, rigidity and bradykinesia, result from neurotransmitter imbalance, particularly the catecholamines dopamine (DA) and noradrenaline. We report in human brain and human SH-SY5Y neuroblastoma cell lines that DJ-1 predominantly forms high molecular weight (HMW) complexes that included RNA metabolism proteins hnRNPA1 and PABP1 and the glycolysis enzyme GAPDH. In cell culture models the oxidation status of DJ-1 determined the specific complex composition. RNA sequencing indicated that oxidative changes to DJ-1 were concomitant with changes in mRNA transcripts mainly involved in catecholamine metabolism. Importantly, loss of DJ-1 function upon knock down (KD) or expression of the PD associated form L166P resulted in the absence of HMW DJ-1 complexes. In the KD model, the absence of DJ-1 complexes was accompanied by impairment in catecholamine homeostasis, with significant increases in intracellular DA and noraderenaline levels. These changes in catecholamines could be rescued by re-expression of DJ-1. This catecholamine imbalance may contribute to the particular vulnerability of dopaminergic and noradrenergic neurons to neurodegeneration in PARK7-related PD. Notably, oxidised DJ-1 was significantly decreased in idiopathic PD brain, suggesting altered complex function may also play a role in the more common sporadic form of the disease.

Cryogen-free dissolution dynamic nuclear polarization polarizer operating at 3.35 T, 6.70 T, and 10.1 T.

PURPOSE: A novel dissolution dynamic nuclear polarization (dDNP) polarizer platform is presented. The polarizer meets a number of key requirements for in vitro, preclinical, and clinical applications. METHOD: It uses no liquid cryogens, operates in continuous mode, accommodates a wide range of sample sizes up to and including those required for human studies, and is fully automated. RESULTS: It offers a wide operational window both in terms of magnetic field, up to 10.1 T, and temperature, from room temperature down to 1.3 K. The polarizer delivers a 13 C liquid state polarization for [1-13 C]pyruvate of 70%. The build-up time constant in the solid state is approximately 1200 s (20 minutes), allowing a sample throughput of at least one sample per hour including sample loading and dissolution. CONCLUSION: We confirm the previously reported strong field dependence in the range 3.35 to 6.7 T, but see no further increase in polarization when increasing the magnetic field strength to 10.1 T for [1-13 C]pyruvate and trityl. Using a custom dry magnet, cold head and recondensing, closed-cycle cooling system, combined with a modular DNP probe, and automation and fluid handling systems, we have designed a unique dDNP system with unrivalled flexibility and performance.

Coil profile estimation strategies for parallel imaging with hyperpolarized 13 C MRI.

PURPOSE: To investigate auto- and pre-calibration coil profile estimation for parallel imaging reconstruction of hyperpolarized 13 C MRI volumetric data. METHODS: Parallel imaging reconstruction was studied with 3 different approaches for coil profile estimation: auto-calibration, phantom calibration, and theoretic calibration. Acquisition was performed with a 3D stack-of-spirals sequence with spectral-spatial excitation and Cartesian undersampling. Parallel imaging reconstructions were done with conjugate gradient SENSE and 3D gridding with inhomogeneity correction. The approaches were compared in simulations with different SNR, through phantom experiments, and in an in vivo pig study focused on the kidneys. All imaging was done with a rigid home-built 12-channel 13 C receive coil at 3T. RESULTS: The phantom calibrated and theoretic approaches resulted in the best structural similarities in simulations and demonstrated higher image quality in the phantom experiments compared to the auto-calibrated approach. In vivo mapping of pyruvate uptake and lactate conversion improved for accelerated acquisitions because of a better temporal resolution. From a practical and image quality point of view, use of theoretic coil profiles led to improved results compared to the other approaches. CONCLUSION: The success of the theoretic coil profile estimation demonstrates a negligible effect of load on sensitivity profiles at the carbon frequency at 3T. Through theoretic or phantom calibrated parallel imaging, accelerated 3D volumes could be reconstructed with sufficient sensitivity, temporal, and spatial resolution to map the metabolism of kidneys exemplifying abdominal organs. This approach overcomes a critical step in the clinical translation of parallel imaging in hyperpolarized 13 C MR.