3D quantitative myocardial perfusion imaging with hyperpolarized HP001(bis-1,1-(hydroxymethyl)-[1-13C]cyclopropane-d8): Application of gradient echo and balanced SSFP sequences.

PURPOSE: This study aims to show the viability of conducting three-dimensional (3D) myocardial perfusion quantification covering the entire heart using both GRE and bSSFP sequences with hyperpolarized HP001. METHODS: A GRE sequence and a bSSFP sequence, both with a stack-of-spirals readout, were designed and applied to three pigs. The images were reconstructed using 13 $$ {}^{13} $$ C coil sensitivity maps measured in a phantom experiment. Perfusion was quantified using a constrained decomposition method, and the estimated rest/stress perfusion values from 13 $$ {}^{13} $$ C GRE/bSSFP and Dynamic contrast-enhanced MRI (DCE-MRI) were individually analyzed through histograms and the mean perfusion values were compared with reference values obtained from PET( 15 $$ {}^{15} $$ O-water). The Myocardial Perfusion Reserve Index (MPRI) was estimated for 13 $$ {}^{13} $$ C GRE/bSSFP and DCE-MRI and compared with the reference values. RESULTS: Perfusion values, estimated by both DCE and 13 $$ {}^{13} $$ C MRI, were found to be lower than reference values. However, DCE-MRI's estimated perfusion values were closer to the reference values than those obtained from 13 $$ {}^{13} $$ C MRI. In the case of MPRI estimation, the 13 $$ {}^{13} $$ C estimated MPRI values (GRE/bSSFP: 2.3/2.0) more closely align with the literature value (around 3) than the DCE estimated MPRI value (1.6). CONCLUSION: This study demonstrated the feasibility of 3D whole-heart myocardial perfusion quantification using hyperpolarized HP001 with both GRE and bSSFP sequences. The 13 $$ {}^{13} $$ C perfusion measurements underestimated perfusion values compared to the 15 $$ {}^{15} $$ O PET literature value, while the 13 $$ {}^{13} $$ C estimated MPRI value aligned better with the literature. This preliminary result indicates 13 $$ {}^{13} $$ C imaging may more accurately estimate MPRI values compared to DCE-MRI.

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.

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.

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.

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.

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.

Sensitive optomechanical transduction of electric and magnetic signals to the optical domain.

We report a radio-frequency-to-optical converter based on an electro-optomechanical transduction scheme where the electrical, optical, and mechanical interface was integrated on a chip and operated with a fiber-coupled optical setup. The device was designed for field tests in a magnetic resonance scanner where its small form-factor and simple operation is paramount. For the appurtenant magnetic resonance detection circuit at 32 MHz, we demonstrate transduction with an intrinsic magnetic field sensitivity of 8 fT/Hz, noise figure 2.3 dB, noise temperature 210 K, voltage noise 99 pV/Hz, and current noise 113 pA/Hz, all in a 3 dB-bandwidth of 12 kHz. Such sensitivity and bandwidth make the transducer a valuable alternative to conventional electronic preamplifiers that additionally is directly compatible with fiber communication networks.

Design of a local quasi-distributed tuning and matching circuit for dissolution DNP cross polarization.

Dynamic nuclear polarization (DNP) build-up times at low temperature for low-gamma nuclei can be unfavorably long and can be accelerated by transfer of polarization from protons. The efficiency of the cross polarization (CP) depends on the B1-field strengths, the pulse sequence chosen for cross polarization and the sample composition. CP experiments rely on high B1-fields, which typically lead to electrical discharge and breakdown in the circuit. This problem is particularly severe in the low pressure helium atmosphere due to easily ionized helium atoms. The purpose of this study is to identify strategies to minimize voltages across components in a tuning and matching circuit of the coil to avoid electrical discharge during CP experiments. Design equations for three tuning and matching network configurations are derived. The results of the study are then used in the design of a single coil double resonance DNP probe operating at 71.8 MHz (13C frequency) and 285.5 MHz (1H frequency). In the current setup we achieve 28% polarization on 13C in urea with a build-up time of 11.6 min with CP compared to 14% and 53 min by direct polarization using TEMPOL as the radical. Different cross polarization sequences are compared.

Efficient Hyperpolarization of U-13 C-Glucose Using Narrow-Line UV-Generated Labile Free Radicals.

Free radicals generated by UV-light irradiation of a frozen solution containing a fraction of pyruvic acid (PA) have demonstrated their dissolution dynamic nuclear polarization (dDNP) potential, providing up to 30 % [1-13 C]PA liquid-state polarization. Moreover, their labile nature has proven to pave a way to nuclear polarization storage and transport. Herein, differently from the case of PA, the issue of providing dDNP UV-radical precursors (trimethylpyruvic acid and its methyl-deuterated form) not involved in any metabolic pathway was investigated. The 13 C dDNP performance was evaluated for hyperpolarization of [U-13 C6 ,1,2,3,4,5,6,6-d7 ]-d-glucose. The generated UV-radicals proved to be versatile and highly efficient polarizing agents, providing, after dissolution and transfer (10 s), a 13 C liquid-state polarization of up to 32 %.

Discovery of Intermediates of lacZ ß-Galactosidase Catalyzed Hydrolysis Using dDNP NMR.

Using dissolution dynamic nuclear polarization, the sensitivity of single scan solution state 13C NMR can be improved up to 4 orders of magnitude. In this study, the enzyme lacZ ß-galactosidase from Escherichia coli was subjected to hyperpolarized substrate, and previously unknown reaction intermediates were observed, including a 1,1-linked disaccharide. The enzyme is known for making 1,6-transglycosylation, producing products like allolactose, that are also substrates. To analyze the kinetics, a simple kinetic model was developed and used to determine relative transglycosylation and hydrolysis rates of each of the intermediates, and the novel transglycosylation intermediates were determined as better substrates than the 1,6-linked one, explaining their transient nature. These findings suggest that hydrolysis and transglycosylation might be more complex than previously described.

Stable Isotope-Resolved Analysis with Quantitative Dissolution Dynamic Nuclear Polarization.

Metabolite profiles and their isotopomer distributions can be studied noninvasively in complex mixtures with NMR. The advent of dissolution Dynamic Nuclear Polarization (dDNP) and isotope enrichment add sensitivity and resolution to such metabolic studies. Metabolic pathways and networks can be mapped and quantified if protocols that control and exploit the ex situ signal enhancement are created. We present a sample preparation method, including cell incubation, extraction and signal enhancement, to obtain reproducible and quantitative dDNP (qdDNP) NMR-based stable isotope-resolved analysis. We further illustrate how qdDNP was applied to gain metabolic insights into the phenotype of aggressive cancer cells.

Antioxidant treatment attenuates lactate production in diabetic nephropathy.

The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-13C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying increased lactate dehydrogenase activity as a consequence of increased nicotinamide adenine dinucleotide substrate availability due to upregulation of the polyol pathway, i.e., pseudohypoxia. In this study, we investigated the role of oxidative stress in mediating these metabolic alterations using state-of-the-art hyperpolarized magnetic resonance (MR) imaging. Ten-week-old female Wistar rats were randomly divided into three groups: healthy controls, untreated diabetic (streptozotocin treatment to induce insulinopenic diabetes), and diabetic, receiving chronic antioxidant treatment with TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) via the drinking water. Examinations were performed 2, 3, and 4 wk after the induction of diabetes by using a 3T Clinical MR system equipped with a dual tuned 13C/1H-volume rat coil. The rats received intravenous hyperpolarized [1-13C]pyruvate and were imaged using a slice-selective 13C-IDEAL spiral sequence. Untreated diabetic rats showed increased renal lactate production compared with that shown by the controls. However, chronic TEMPOL treatment significantly attenuated diabetes-induced lactate production. No significant effects of diabetes or TEMPOL were observed on [13C]alanine levels, indicating an intact glucose-alanine cycle, or [13C]bicarbonate, indicating normal flux through the Krebs cycle. In conclusion, this study demonstrates that diabetes-induced pseudohypoxia, as indicated by an increased lactate-to-pyruvate ratio, is significantly attenuated by antioxidant treatment. This demonstrates a pivotal role of oxidative stress in renal metabolic alterations occurring in early diabetes.

Renal MR angiography and perfusion in the pig using hyperpolarized water.

PURPOSE: To study hyperpolarized water as an angiography and perfusion tracer in a large animal model. METHODS: Protons dissolved in deuterium oxide (D2 O) were hyperpolarized in a SPINlab dissolution dynamic nuclear polarization (dDNP) polarizer and subsequently investigated in vivo in a pig model at 3 Tesla (T). Approximately 15 mL of hyperpolarized water was injected in the renal artery by hand over 4-5 s. RESULTS: A liquid state polarization of 5.3 ± 0.9% of 3.8 M protons in 15 mL of deuterium oxide was achieved with a T1 of 24 ± 1 s. This allowed injection through an arterial catheter into the renal artery and subsequently high-contrast imaging of the entire kidney parenchyma over several seconds. The dynamic images allow quantification of tissue perfusion, with a mean cortical perfusion of 504 ± 123 mL/100 mL/min. CONCLUSION: Hyperpolarized water MR imaging was successfully demonstrated as a renal angiography and perfusion method. Quantitative perfusion maps of the kidney were obtained in agreement with literature and control experiments with gadolinium contrast. Magn Reson Med 78:1131-1135, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Simultaneous imaging of hyperpolarized [1,4-13 C2 ]fumarate, [1-13 C]pyruvate and 18 F-FDG in a rat model of necrosis in a clinical PET/MR scanner.

A co-polarization scheme for [1,4-13 C2 ]fumarate and [1-13 C]pyruvate is presented to simultaneously assess necrosis and metabolism in rats with hyperpolarized 13 C magnetic resonance (MR). The co-polarization was performed in a SPINlab polarizer. In addition, the feasibility of simultaneous positron emission tomography (PET) and MR of small animals with a clinical PET/MR scanner is demonstrated. The hyperpolarized metabolic MR and PET was demonstrated in a rat model of necrosis. The polarization and T1 of the co-polarized [1,4-13 C2 ]fumarate and [1-13 C]pyruvate substrates were measured in vitro and compared with those obtained when the substrates were polarized individually. A polarization of 36 ± 4% for fumarate and 37 ± 6% for pyruvate was obtained. We found no significant difference in the polarization and T1 values between the dual and single substrate polarization. Rats weighing about 400 g were injected intramuscularly in one of the hind legs with 200 µL of turpentine to induce necrosis. Two hours later, 13 C metabolic maps were obtained with a chemical shift imaging sequence (16 × 16) with a resolution of 3.1 × 5.0 × 25.0 mm3 . The 13 C spectroscopic images were acquired in 12 s, followed by an 8-min 18 F-2-fluoro-2-deoxy-d-glucose (18 F-FDG) PET acquisition with a resolution of 3.5 mm. [1,4-13 C2 ]Malate was observed from the tissue injected with turpentine indicating necrosis. Normal [1-13 C]pyruvate metabolism and 18 F-FDG uptake were observed from the same tissue. The proposed co-polarization scheme provides a means to utilize multiple imaging agents simultaneously, and thus to probe various metabolic pathways in a single examination. Moreover, it demonstrates the feasibility of small animal research on a clinical PET/MR scanner for combined PET and hyperpolarized metabolic MR.