Multi-band echo-planar spectroscopic imaging of hyperpolarized 13 C probes in a compact preclinical PET/MR scanner.

PURPOSE: Hyperpolarized (HP) 13 C MRI has enabled real-time imaging of specific enzyme-catalyzed metabolic reactions, but advanced pulse sequences are necessary to capture the dynamic, localized metabolic information. Herein we describe the design, implementation, and testing of a rapid and efficient HP 13 C pulse sequence strategy on a cryogen-free simultaneous positron emission tomography/MR molecular imaging platform with compact footprint. METHODS: We developed an echo planar spectroscopic imaging pulse sequence incorporating multi-band spectral-spatial radiofrequency (SSRF) pulses for spatially coregistered excitation of 13 C metabolites with differential individual flip angles. Excitation profiles were measured in phantoms, and the SSRF-echo planar spectroscopic imaging sequence was tested in rats in vivo and compared to conventional echo planar spectroscopic imaging. The new sequence was applied for 2D dynamic metabolic imaging of HP [1-13 C]pyruvate and its molecular analog [1-13 C] α -ketobutyrate at a spatial resolution of 5 mm × 5 mm × 20 mm and temporal resolution of 4 s. We also obtained simultaneous 18 F-fluorodeoxyglucose positron emission tomography data for comparison with HP [1-13 C]pyruvate data acquired during the same scan session. RESULTS: Measured SSRF excitation profiles corresponded well to Bloch simulations. Multi-band SSRF excitation facilitated efficient sampling of the multi-spectral kinetics of [1-13 C]pyruvate and [1-13 C] α - ketobutyrate . Whereas high pyruvate to lactate conversion was observed in liver, corresponding reduction of α -ketobutyrate to [1-13 C] α -hydroxybutyrate ( α HB) was largely restricted to the kidneys and heart, consistent with the known expression pattern of lactate dehydrogenase B. CONCLUSION: Advanced 13 C SSRF imaging approaches are feasible on our compact positron emission tomography/MR platform, maximizing the potential of HP 13 C technology and facilitating direct comparison with positron emission tomography.

Dynamic 13 C MR spectroscopy as an alternative to imaging for assessing cerebral metabolism using hyperpolarized pyruvate in humans.

PURPOSE: This study is to investigate time-resolved 13 C MR spectroscopy (MRS) as an alternative to imaging for assessing pyruvate metabolism using hyperpolarized (HP) [1-13 C]pyruvate in the human brain. METHODS: Time-resolved 13 C spectra were acquired from four axial brain slices of healthy human participants (n = 4) after a bolus injection of HP [1-13 C]pyruvate. 13 C MRS with low flip-angle excitations and a multichannel 13 C/1 H dual-frequency radiofrequency (RF) coil were exploited for reliable and unperturbed assessment of HP pyruvate metabolism. Slice-wise areas under the curve (AUCs) of 13 C-metabolites were measured and kinetic analysis was performed to estimate the production rates of lactate and HCO3- . Linear regression analysis between brain volumes and HP signals was performed. Region-focused pyruvate metabolism was estimated using coil-wise 13 C reconstruction. Reproducibility of HP pyruvate exams was presented by performing two consecutive injections with a 45-minutes interval. RESULTS: [1-13 C]Lactate relative to the total 13 C signal (tC) was 0.21-0.24 in all slices. [13 C] HCO3- /tC was 0.065-0.091. Apparent conversion rate constants from pyruvate to lactate and HCO3- were calculated as 0.014-0.018 s-1 and 0.0043-0.0056 s-1 , respectively. Pyruvate/tC and lactate/tC were in moderate linear relationships with fractional gray matter volume within each slice. White matter presented poor linear regression fit with HP signals, and moderate correlations of the fractional cerebrospinal fluid volume with pyruvate/tC and lactate/tC were measured. Measured HP signals were comparable between two consecutive exams with HP [1-13 C]pyruvate. CONCLUSIONS: Dynamic MRS in combination with multichannel RF coils is an affordable and reliable alternative to imaging methods in investigating cerebral metabolism using HP [1-13 C]pyruvate.

Hyperpolarized 13C MR Spectroscopy Depicts in Vivo Effect of Exercise on Pyruvate Metabolism in Human Skeletal Muscle.

Background Pyruvate dehydrogenase (PDH) and lactate dehydrogenase are essential for adenosine triphosphate production in skeletal muscle. At the onset of exercise, oxidation of glucose and glycogen is quickly enabled by dephosphorylation of PDH. However, direct measurement of PDH flux in exercising human muscle is daunting, and the net effect of covalent modification and other control mechanisms on PDH flux has not been assessed. Purpose To demonstrate the feasibility of assessing PDH activation and changes in pyruvate metabolism in human skeletal muscle after the onset of exercise using carbon 13 (13C) MRI with hyperpolarized (HP) [1-13C]-pyruvate. Materials and Methods For this prospective study, sedentary adults in good general health (mean age, 42 years ± 18 [standard deviation]; six men) were recruited from August 2019 to September 2020. Subgroups of the participants were injected with HP [1-13C]-pyruvate at resting, during plantar flexion exercise, or 5 minutes after exercise during recovery. In parallel, hydrogen 1 arterial spin labeling MRI was performed to estimate muscle tissue perfusion. An unpaired t test was used for comparing 13C data among the states. Results At rest, HP [1-13C]-lactate and [1-13C]-alanine were detected in calf muscle, but [13C]-bicarbonate was negligible. During moderate flexion-extension exercise, total HP 13C signals (tC) increased 2.8-fold because of increased muscle perfusion (P = .005), and HP [1-13C]-lactate-to-tC ratio increased 1.7-fold (P = .04). HP [13C]-bicarbonate-to-tC ratio increased 8.4-fold (P = .002) and returned to the resting level 5 minutes after exercise, whereas the lactate-to-tC ratio continued to increase to 2.3-fold as compared with resting (P = .008). Conclusion Lactate and bicarbonate production from hyperpolarized (HP) [1-carbon 13 {13C}]-pyruvate in skeletal muscle rapidly reflected the onset and the termination of exercise. These results demonstrate the feasibility of imaging skeletal muscle metabolism using HP [1-13C]-pyruvate MRI and the sensitivity of in vivo pyruvate metabolism to exercise states. © RSNA, 2021 Online supplemental material is available for this article.

Comparison of hyperpolarized 13 C and non-hyperpolarized deuterium MRI approaches for imaging cerebral glucose metabolism at 4.7 T.

PURPOSE: The purpose of this study was to directly compare two isotopic metabolic imaging approaches, hyperpolarized (HP) 13 C MRI and deuterium metabolic imaging (DMI), for imaging specific closely related segments of cerebral glucose metabolism at 4.7 T. METHODS: Comparative HP-13 C and DMI neuroimaging experiments were conducted consecutively in normal rats during the same scanning session. Localized conversions of [1-13 C]pyruvate and [6,6-2 H2 ]glucose to their respective downstream metabolic products were measured by spectroscopic imaging, using an identical 2D-CSI sequence with parameters optimized for the respective experiments. To facilitate direct comparison, a pair of substantially equivalent 2.5-cm double-tuned X/1 H RF surface coils was developed. For improved results, multidimensional low-rank reconstruction was applied to denoise the raw DMI data. RESULTS: Localized conversion of HP [1-13 C]pyruvate to [1-13 C]lactate, and [6,6-2 H2 ]glucose to [3,3-2 H2 ]lactate and Glx-d (glutamate and glutamine), was detected in rat brain by spectroscopic imaging at 4.7 T. The SNR and spatial resolution of HP-13 C MRI was superior to DMI but limited to a short time window, whereas the lengthy DMI acquisition yielded maps of not only lactate, but also Glx production, albeit with relatively poor spectral discrimination between metabolites at this field strength. Across the individual rats, there was an apparent inverse correlation between cerebral production of HP [1-13 C]lactate and Glx-d, along with a trend toward increased [3,3-2 H2 ]lactate. CONCLUSION: The HP-13 C MRI and DMI methods are both feasible at 4.7 T and have significant potential for metabolic imaging of specific segments of glucose metabolism.

Cardiac T2∗ measurement of hyperpolarized 13 C metabolites using metabolite-selective multi-echo spiral imaging.

PURPOSE: Noninvasive imaging with hyperpolarized (HP) pyruvate can capture in vivo cardiac metabolism. For proper quantification of the metabolites and optimization of imaging parameters, understanding MR characteristics such as T2∗ s of the HP signals is critical. This study is to measure in vivo cardiac T2∗ s of HP [1-13 C]pyruvate and the products in rodents and humans. METHODS: A dynamic 13 C multi-echo spiral imaging sequence that acquires [13 C]bicarbonate, [1-13 C]lactate, and [1-13 C]pyruvate images in an interleaved manner was implemented for a clinical 3 Tesla system. T2∗ of each metabolite was calculated from the multi-echo images by fitting the signal decay of each region of interest mono-exponentially. The performance of measuring T2∗ using the sequence was first validated using a 13 C phantom and then with rodents following a bolus injection of HP [1-13 C]pyruvate. In humans, T2∗ of each metabolite was calculated for left ventricle, right ventricle, and myocardium. RESULTS: Cardiac T2∗ s of HP [1-13 C]pyruvate, [1-13 C]lactate, and [13 C]bicarbonate in rodents were measured as 24.9 ± 5.0, 16.4 ± 4.7, and 16.9 ± 3.4 ms, respectively. In humans, T2∗ of [1-13 C]pyruvate was 108.7 ± 22.6 ms in left ventricle and 129.4 ± 8.9 ms in right ventricle. T2∗ of [1-13 C]lactate was 40.9 ± 8.3, 44.2 ± 5.5, and 43.7 ± 9.0 ms in left ventricle, right ventricle, and myocardium, respectively. T2∗ of [13 C]bicarbonate in myocardium was 64.4 ± 2.5 ms. The measurements were reproducible and consistent over time after the pyruvate injection. CONCLUSION: The proposed metabolite-selective multi-echo spiral imaging sequence reliably measures in vivo cardiac T2∗ s of HP [1-13 C]pyruvate and products.

15 N-carnitine, a novel endogenous hyperpolarized MRI probe with long signal lifetime.

PURPOSE: The purpose of this study was to investigate hyperpolarization and in vivo imaging of [15 N]carnitine, a novel endogenous MRI probe with long signal lifetime. METHODS: L-[15 N]carnitine-d9 was hyperpolarized by the method of dynamic nuclear polarization followed by rapid dissolution. The T1 signal lifetimes were estimated in aqueous solution and in vivo following intravenous injection in rats, using a custom-built dual-tuned 15 N/1 H RF coil at 4.7 T. 15 N chemical shift imaging and 15 N fast spin-echo images of rat abdomen were acquired 3 minutes after [15 N]carnitine injection. RESULTS: Estimated T1 times of [15 N]carnitine at 4.7 T were 210 seconds (in H2 O) and 160 seconds (in vivo), with an estimated polarization level of 10%. Remarkably, the [15 N]carnitine coherence was detectable in rat abdomen for 5 minutes after injection for the nonlocalized acquisition. No downstream metabolites were detected on localized or nonlocalized 15 N spectra. Diffuse liver enhancement was detected on 15 N fast spin-echo imaging 3 minutes after injection, with mean hepatic SNR of 18 ± 5 at a spatial resolution of 4 × 4 mm. CONCLUSION: This study showed the feasibility of hyperpolarizing and imaging the biodistribution of HP [15 N]carnitine.

Characterization and compensation of f0 inhomogeneity artifact in spiral hyperpolarized 13 C imaging of the human heart.

PURPOSE: This study aimed to investigate the role of regional f0 inhomogeneity in spiral hyperpolarized 13 C image quality and to develop measures to alleviate these effects. METHODS: Field map correction of hyperpolarized 13 C cardiac imaging using spiral readouts was evaluated in healthy subjects. Spiral readouts with differing duration (26 and 45 ms) but similar resolution were compared with respect to off-resonance performance and image quality. An f0 map-based image correction based on the multifrequency interpolation (MFI) method was implemented and compared to correction using a global frequency shift alone. Estimation of an unknown frequency shift was performed by maximizing a sharpness objective based on the Sobel variance. The apparent full width half at maximum (FWHM) of the myocardial wall on [13 C]bicarbonate was used to estimate blur. RESULTS: Mean myocardial wall FWHM measurements were unchanged with the short readout pre-correction (14.1 ± 2.9 mm) and post-MFI correction (14.1 ± 3.4 mm), but significantly decreased in the long waveform (20.6 ± 6.6 mm uncorrected, 17.7 ± 7.0 corrected, P = .007). Bicarbonate signal-to-noise ratio (SNR) of the images acquired with the long waveform were increased by 1.4 ± 0.3 compared to those acquired with the short waveform (predicted 1.32). Improvement of image quality was observed for all metabolites with f0 correction. CONCLUSIONS: f0 -map correction reduced blur and recovered signal from dropouts, particularly along the posterior myocardial wall. The low image SNR of [13 C]bicarbonate can be compensated with longer duration readouts but at the expense of increased f0 artifacts, which can be partially corrected for with the proposed methods.

Tensor image enhancement and optimal multichannel receiver combination analyses for human hyperpolarized 13 C MRSI.

PURPOSE: With the initiation of human hyperpolarized 13 C (HP-13 C) trials at multiple sites and the development of improved acquisition methods, there is an imminent need to maximally extract diagnostic information to facilitate clinical interpretation. This study aims to improve human HP-13 C MR spectroscopic imaging through means of Tensor Rank truncation-Image enhancement (TRI) and optimal receiver combination (ORC). METHODS: A data-driven processing framework for dynamic HP 13 C MR spectroscopic imaging (MRSI) was developed. Using patient data sets acquired with both multichannel arrays and single-element receivers from the brain, abdomen, and pelvis, we examined the theory and application of TRI, as well as 2 ORC techniques: whitened singular value decomposition (WSVD) and first-point phasing. Optimal conditions for TRI were derived based on bias-variance trade-off. RESULTS: TRI and ORC techniques together provided a 63-fold mean apparent signal-to-noise ratio (aSNR) gain for receiver arrays and a 31-fold gain for single-element configurations, which particularly improved quantification of the lower-SNR-[13 C]bicarbonate and [1-13 C]alanine signals that were otherwise not detectable in many cases. Substantial SNR enhancements were observed for data sets that were acquired even with suboptimal experimental conditions, including delayed (114 s) injection (8× aSNR gain solely by TRI), or from challenging anatomy or geometry, as in the case of a pediatric patient with brainstem tumor (597× using combined TRI and WSVD). Improved correlation between elevated pyruvate-to-lactate conversion, biopsy-confirmed cancer, and mp-MRI lesions demonstrated that TRI recovered quantitative diagnostic information. CONCLUSION: Overall, this combined approach was effective across imaging targets and receiver configurations and could greatly benefit ongoing and future HP 13 C MRI research through major aSNR improvements.

In vivo hyperpolarization transfer in a clinical MRI scanner.

PURPOSE: The purpose of this study was to investigate the feasibility of in vivo 13 C->1 H hyperpolarization transfer, which has significant potential advantages for detecting the distribution and metabolism of hyperpolarized 13 C probes in a clinical MRI scanner. METHODS: A standalone pulsed 13 C RF transmit channel was developed for operation in conjunction with the standard 1 H channel of a clinical 3T MRI scanner. Pulse sequences for 13 C power calibration and polarization transfer were programmed on the external hardware and integrated with a customized water-suppressed 1 H MRS acquisition running in parallel on the scanner. The newly developed RF system was tested in both phantom and in vivo polarization transfer experiments in 1 JCH -coupled systems: phantom experiments in thermally polarized and hyperpolarized [2-13 C]glycerol, and 1 H detection of [2-13 C]lactate generated from hyperpolarized [2-13 C]pyruvate in rat liver in vivo. RESULTS: Operation of the custom pulsed 13 C RF channel resulted in effective 13 C->1 H hyperpolarization transfer, as confirmed by the characteristic antiphase appearance of 1 H-detected, 1 JCH -coupled doublets. In conjunction with a pulse sequence providing 190-fold water suppression in vivo, 1 H detection of hyperpolarized [2-13 C]lactate generated in vivo was achieved in a rat liver slice. CONCLUSION: The results show clear feasibility for effective 13 C->1 H hyperpolarization transfer in a clinical MRI scanner with customized heteronuclear RF system.

Spectrally selective three-dimensional dynamic balanced steady-state free precession for hyperpolarized C-13 metabolic imaging with spectrally selective radiofrequency pulses.

PURPOSE: Balanced steady-state free precession (bSSFP) sequences can provide superior signal-to-noise ratio efficiency for hyperpolarized (HP) carbon-13 (13 C) magnetic resonance imaging by efficiently utilizing the nonrecoverable magnetization, but managing their spectral response is challenging in the context of metabolic imaging. A new spectrally selective bSSFP sequence was developed for fast imaging of multiple HP 13 C metabolites with high spatiotemporal resolution. THEORY AND METHODS: This novel approach for bSSFP spectral selectivity incorporates optimized short-duration spectrally selective radiofrequency pulses within a bSSFP pulse train and a carefully chosen repetition time to avoid banding artifacts. RESULTS: The sequence enabled subsecond 3D dynamic spectrally selective imaging of 13 C metabolites of copolarized [1-13 C]pyruvate and [13 C]urea at 2-mm isotropic resolution, with excellent spectral selectivity (∼100:1). The sequence was successfully tested in phantom studies and in vivo studies with normal mice. CONCLUSION: This sequence is expected to benefit applications requiring dynamic volumetric imaging of metabolically active 13 C compounds at high spatiotemporal resolution, including preclinical studies at high field and, potentially, clinical studies. Magn Reson Med 78:963-975, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Rapid in vivo apparent diffusion coefficient mapping of hyperpolarized (13) C metabolites.

PURPOSE: Hyperpolarized (13) C magnetic resonance allows for the study of real-time metabolism in vivo, including significant hyperpolarized (13) C lactate production in many tumors. Other studies have shown that aggressive and highly metastatic tumors rapidly transport lactate out of cells. Thus, the ability to not only measure the production of hyperpolarized (13) C lactate but also understand its compartmentalization using diffusion-weighted MR will provide unique information for improved tumor characterization. METHODS: We used a bipolar, pulsed-gradient, double spin echo imaging sequence to rapidly generate diffusion-weighted images of hyperpolarized (13) C metabolites. Our methodology included a simultaneously acquired B1 map to improve apparent diffusion coefficient (ADC) accuracy and a diffusion-compensated variable flip angle scheme to improve ADC precision. RESULTS: We validated this sequence and methodology in hyperpolarized (13) C phantoms. Next, we generated ADC maps of several hyperpolarized (13) C metabolites in a normal rat, rat brain tumor, and prostate cancer mouse model using both preclinical and clinical trial-ready hardware. CONCLUSION: ADC maps of hyperpolarized (13) C metabolites provide information about the localization of these molecules in the tissue microenvironment. The methodology presented here allows for further studies to investigate ADC changes due to disease state that may provide unique information about cancer aggressiveness and metastatic potential.

Chemical shift separation with controlled aliasing for hyperpolarized (13) C metabolic imaging.

PURPOSE: A chemical shift separation technique for hyperpolarized (13) C metabolic imaging with high spatial and temporal resolution was developed. Specifically, a fast three-dimensional pulse sequence and a reconstruction method were implemented to acquire signals from multiple (13) C species simultaneously with subsequent separation into individual images. THEORY AND METHODS: A stack of flyback echo-planar imaging readouts and a set of multiband excitation radiofrequency pulses were designed to spatially modulate aliasing patterns of the acquired metabolite images, which translated the chemical shift separation problem into parallel imaging reconstruction problem. An eight-channel coil array was used for data acquisition and a parallel imaging method based on nonlinear inversion was developed to separate the aliased images. RESULTS: Simultaneous acquisitions of pyruvate and lactate in a phantom study and in vivo rat experiments were performed. The results demonstrated successful separation of the metabolite distributions into individual images having high spatial resolution. CONCLUSION: This method demonstrated the ability to provide accelerated metabolite imaging in hyperpolarized (13) C MR using multichannel coils, tailored readout, and specialized RF pulses.

Simultaneous multiagent hyperpolarized (13)C perfusion imaging.

PURPOSE: To demonstrate simultaneous hyperpolarization and imaging of three (13)C-labeled perfusion MRI contrast agents with dissimilar molecular structures ([(13)C]urea, [(13)C]hydroxymethyl cyclopropane, and [(13)C]t-butanol) and correspondingly variable chemical shifts and physiological characteristics, and to exploit their varying diffusibility for simultaneous measurement of vascular permeability and perfusion in initial preclinical studies. METHODS: Rapid and efficient dynamic multislice imaging was enabled by a novel pulse sequence incorporating balanced steady state free precession excitation and spectral-spatial readout by multiband frequency encoding, designed for the wide, regular spectral separation of these compounds. We exploited the varying bilayer permeability of these tracers to quantify vascular permeability and perfusion parameters simultaneously, using perfusion modeling methods that were investigated in simulations. "Tripolarized" perfusion MRI methods were applied to initial preclinical studies with differential conditions of vascular permeability, in normal mouse tissues and advanced transgenic mouse prostate tumors. RESULTS: Dynamic imaging revealed clear differences among the individual tracer distributions. Computed permeability maps demonstrated differential permeability of brain tissue among the tracers, and tumor perfusion and permeability were both elevated over values expected for normal tissues. CONCLUSION: Tripolarized perfusion MRI provides new molecular imaging measures for specifically monitoring permeability, perfusion, and transport simultaneously in vivo.

Multiparametric 3T endorectal mri after external beam radiation therapy for prostate cancer.

PURPOSE: To determine the best combination of magnetic resonance imaging (MRI) parameters for the detection of locally recurrent prostate cancer after external beam radiation therapy. MATERIALS AND METHODS: Our Institutional Review Board approved this study with a waiver of informed consent. Twenty-six patients with suspected recurrence due to biochemical failure were part of this research. The MR protocol included T2-weighted, MR spectroscopy, and diffusion-weighted MRI. Transrectal ultrasound-guided biopsy was the standard of reference. We used logistic regression to model the probability of a positive outcome and generalized estimating equations to account for clustering. The diagnostic performance of imaging was described using receiver operating characteristic (ROC) curves. RESULTS: The area under the ROC curve of MR spectroscopic imaging (MRSI) was 83.0% (95% confidence interval [CI] = 75.5-89.1). The combination of all MR techniques did not significantly improve the performance of imaging beyond the accuracy of MRSI alone, but a trend toward improved discrimination was noted (86.9%; 95% CI = 77.6-93.4; P = 0.09). CONCLUSION: Incorporation of MRSI to T2-weighted and/or diffusion-weighted MRI significantly improves the assessment of patients with suspected recurrence after radiotherapy and a combined approach with all three modalities may have the best diagnostic performance.

Hyperpolarized Carbon (13C) MRI of the Kidney: Experimental Protocol.

Alterations in renal metabolism are associated with both physiological and pathophysiologic events. The existing noninvasive analytic tools including medical imaging have limited capability for investigating these processes, which potentially limits current understanding of kidney disease and the precision of its clinical diagnosis. Hyperpolarized 13C MRI is a new medical imaging modality that can capture changes in the metabolic processing of certain rapidly metabolized substrates, as well as changes in kidney function. Here we describe experimental protocols for renal metabolic [1-13C]pyruvate and functional 13C-urea imaging step-by-step. These methods and protocols are useful for investigating renal blood flow and function as well as the renal metabolic status of rodents in vivo under various experimental (patho)physiological conditions.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol is complemented by two separate chapters describing the basic concept and data analysis.

Analysis Methods for Hyperpolarized Carbon (13C) MRI of the Kidney.

Hyperpolarized 13C MR is a novel medical imaging modality with substantially different signal dynamics as compared to conventional 1H MR, thus requiring new methods for processing the data in order to access and quantify the embedded metabolic and functional information. Here we describe step-by-step analysis protocols for functional renal hyperpolarized 13C imaging. These methods are useful for investigating renal blood flow and function as well as metabolic status of rodents in vivo under various experimental physiological conditions.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

Metabolite-Specific Echo-Planar Imaging of Hyperpolarized [1-13C]Pyruvate at 4.7 T.

Although hyperpolarization (HP) greatly increases the sensitivity of 13C MR, the usefulness of HP in vivo is limited by the short lifetime of HP agents. To address this limitation, we developed an echo-planar (EPI) sequence with spectral-spatial radiofrequency (SSRF) pulses for fast and efficient metabolite-specific imaging of HP [1-13C]pyruvate and [1-13C]lactate at 4.7 T. The spatial and spectral selectivity of each SSRF pulse was verified using simulations and phantom testing. EPI and CSI imaging of the rat abdomen were compared in the same rat after injecting HP [1-13C]pyruvate. A procedure was also developed to automatically set the SSRF excitation pulse frequencies based on real-time scanner feedback. The most significant results of this study are the demonstration that a greater spatial and temporal resolution is attainable by metabolite-specific EPI as compared with CSI, and the enhanced lifetime of the HP signal in EPI, which is attributable to the independent flip angle control between metabolites. Real-time center frequency adjustment was also highly effective for minimizing off-resonance effects. To the best of our knowledge, this is the first demonstration of metabolite-specific HP 13C EPI at 4.7 T. In conclusion, metabolite-specific EPI using SSRF pulses is an effective way to image HP [1-13C]pyruvate and [1-13C]lactate at 4.7 T.

Hyperpolarized Carbon (13C) MRI of the Kidneys: Basic Concept.

Existing clinical markers for renal disease are limited. Hyperpolarized (HP) 13C MRI is based on the technology of dissolution dynamic nuclear polarization (DNP) and provides new avenues for imaging kidney structure, function, and most notably, renal metabolism, addressing some of these prior limitations. Changes in kidney structure and function associated with kidney disease can be evaluated using [13C]urea, a metabolically inert tracer. Metabolic changes can be assessed using [1-13C]pyruvate and a range of other rapidly metabolized small molecules, which mainly probe central carbon metabolism. Results from numerous preclinical studies using a variety of these probes demonstrated that this approach holds great potential for monitoring renal disease, although more work is needed to bridge intelligently into clinical studies. Here we introduce the general concept of HP 13C MRI and review the most relevant probes and applications to renal disease, including kidney cancer, diabetic nephropathy and ischemic kidney injury.This chapter is based upon work from the PARENCHIMA COST Action, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

The effect of transmit B1 inhomogeneity on hyperpolarized [1-13 C]-pyruvate metabolic MR imaging biomarkers.

PURPOSE: A specialized Helmholtz-style 13 C volume transmit "clamshell" coil is currently being utilized for 13 C excitation in pre-clinical and clinical hyperpolarized 13 C MRI studies aimed at probing the metabolic activity of tumors in various target anatomy. Due to the widespread use of this 13 C clamshell coil design, it is important that the effects of the 13 C clamshell coil B1 + profile on HP signal evolution and quantification are well understood. The goal of this study was to characterize the B1 + field of the 13 C clamshell coil and assess the impact of inhomogeneities on semi-quantitative and quantitative hyperpolarized MR imaging biomarkers of metabolism. METHODS: The B1 + field of the 13 C clamshell coil was mapped by hand using a network analyzer equipped with an S-parameter test set. Pharmacokinetic models were used to simulate signal evolution as a function of position-dependent local excitation angles, for various nominal excitation angles, which were assumed to be accurately calibrated at the isocenter. These signals were then quantified according to the normalized lactate ratio (nLac) and the apparent rate constant for the conversion of pyruvate to lactate (kPL ). The percent difference between these metabolic imaging biomarker maps and the reference value observed at the isocenter of the clamshell coil was calculated to estimate the potential for error due to position within the clamshell coil. Finally, regions were identified within the clamshell coil where deviations in B1 + field inhomogeneity or imaging biomarker errors imparted by the B1 + field were within ±10% of the value at the isocenter. RESULTS: The B1 + field maps show that a limited volume encompassed by a region measuring approximately 12.9 × 11.5 × 13.4 cm (X-direction, Y-direction, Z-direction) centered in the 13 C clamshell coil will produce deviations in the B1 + field within ±10% of that at the isocenter. For the metabolic imaging biomarkers that we evaluated, the case when the pyruvate excitation angle (θP ) and lactate excitation angle (θL ) were equal to 10° produced the largest volumetric region with deviations within ±10% of the value at the isocenter. Higher excitation angles yielded higher signal and SNR, but the size of the region in which uniform measurements could be collected near the isocenter of the coil was reduced at higher excitation angles. The tradeoff between the size of the homogenous region at the isocenter and signal intensity must be weighed carefully depending on the particular imaging application. CONCLUSION: This work identifies regions and optimal excitation angles (θP and θL ) within the 13 C clamshell coil where deviations in B1 + field inhomogeneity or imaging biomarker errors imparted by the B1 + field were within ±10% of the respective value at the isocenter, and thus where excitation angles are reproducible and well-calibrated. Semi-quantitative and quantitative metabolic imaging biomarkers can vary with position in the clamshell coil as a result of B1 + field inhomogeneity, necessitating care in patient positioning and the selection of an excitation angle set that balances reproducibility and SNR performance over the target imaging volume.