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Background: Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related death in the United States. However, early response assessment using the current approach of measuring changes in tumor size on computed tomography (CT) or MRI is challenging., Purpose: To investigate the feasibility of hyperpolarized (HP) [1- 13 C]pyruvate MRI to quantify metabolism in the normal appearing pancreas and PDA, and to assess changes in PDA metabolism following systemic chemotherapy., Study Type: Prospective., Subjects: Six patients (65.0 ± 7.6 years, 2 females) with locally advanced or metastatic PDA enrolled prior to starting a new line of systemic chemotherapy., Field Strength/sequence: 3-T, T1-weighted gradient echo, metabolite-selective 13 C echoplanar imaging., Assessment: Time-resolved HP [1- 13 C]pyruvate data were acquired before (N = 6) and 4-weeks after (N = 3) treatment initiation. Pyruvate metabolism, as quantified by pharmacokinetic modeling and metabolite area-under-the-curve ratios, was assessed in manually segmented PDA and normal appearing pancreas ROIs (N = 5). The change in tumor metabolism before and 4-weeks after treatment initiation was assessed in primary PDA (N = 2) and liver metastases (N = 1), and was compared to objective tumor response defined by response evaluation criteria in solid tumors (RECIST) on subsequent CTs., Statistical Tests: Descriptive tests (mean ± standard deviation), model fit error for pharmacokinetic rate constants., Results: Primary PDA showed reduced alanine-to-lactate ratios when compared to normal pancreas, due to increased lactate-to-pyruvate or reduced alanine-to-pyruvate ratios. Of the three patients who received HP [1- 13 C]pyruvate MRI before and 4-weeks after treatment initiation, one patient had a primary tumor with early metabolic response (increase in alanine-to-lactate) and subsequent partial response according to RECIST, one patient had a primary tumor with relatively stable metabolism and subsequent stable disease by RECIST, and one patient had metastatic PDA with increase in lactate-to-pyruvate of the liver metastases and corresponding progressive disease according to RECIST., Data Conclusion: Altered pyruvate metabolism with increased lactate or reduced alanine was observed in the primary tumor. Early metabolic response assessed at 4-weeks after treatment initiation correlated with subsequent objective tumor response assessed using RECIST., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Non-alcoholic steatohepatitis (NASH) is characterized from its early stages by a profound remodeling of the liver microenvironment, encompassing changes in the composition and activities of multiple cell types and associated gene expression patterns. Hyperpolarized (HP) 13 C MRI provides a unique view of the metabolic microenvironment, with potential relevance for early diagnosis of liver disease. Previous studies have detected changes in HP 13 C pyruvate to lactate conversion, catalyzed by lactate dehydrogenase (LDH), with experimental liver injury. HP ∝ -ketobutyrate ( ∝ KB) is a close molecular analog of pyruvate with modified specificity for LDH isoforms, specifically attenuated activity with their LDHA-expressed subunits that dominate liver parenchyma. Building on recent results with pyruvate, we investigated HP ∝ KB in methionine-choline deficient (MCD) diet as a model of early-stage NASH. Similarity of results between this new agent and pyruvate (~ 50% drop in cytoplasmic reducing capacity), interpreted together with gene expression data from the model, suggests that changes are mediated through broad effects on intermediary metabolism. Plausible mechanisms are depletion of the lactate pool by upregulation of gluconeogenesis (GNG) and pentose phosphate pathway (PPP) flux, and a possible shift toward increased lactate oxidation. These changes may reflect high levels of oxidative stress and/or shifting macrophage populations in NASH., (© 2024. The Author(s).)

Hyperpolarized carbon-13 magnetic resonance imaging (HP 13 C MRI) is a recently translated metabolic imaging technique. With dissolution dynamic nuclear polarization (d-DNP), more than 10 000-fold signal enhancement can be readily reached, making it possible to visualize real-time metabolism and specific substrate-to-metabolite conversions in the liver after injecting carbon-13 labelled probes. Increasing evidence suggests that HP 13 C MRI is a potential tool in detecting liver abnormalities, predicting disease progression and monitoring response treatment. In this review, we will introduce the recent progresses of HP 13 C MRI in diffuse liver diseases and liver malignancies and discuss its future opportunities from a clinical perspective, hoping to provide a comprehensive overview of this novel technique in liver diseases and highlight its scientific and clinical potential in the field of hepatology., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

Purpose: To develop a novel post-processing pipeline for hyperpolarized (HP) 13 C MRSI that integrates tensor denoising and B 1 + correction to measure pyruvate-to-lactate conversion rates (k PL ) in patients with liver tumors., Methods: Seven HP 13 C MR scans of progressing liver tumors were acquired using a custom 13 C surface transmit/receive coil and the echo-planar spectroscopic imaging (EPSI) data analysis included B 0 correction, tensor rank truncation, and zero- and first-order phase corrections to recover metabolite signals that would otherwise be obscured by spectral noise as well as a correction for inhomogeneous transmit ( B 1 + ) using a B 1 + map aligned to the coil position for each patient scan. Processed HP data and corrected flip angles were analyzed with an inputless two-site exchange model to calculate k PL ., Results: Denoising averages SNR increases of pyruvate, lactate, and alanine were 37.4-, 34.0-, and 20.1-fold, respectively, with lactate and alanine dynamics most noticeably recovered and better defined. In agreement with Monte Carlo simulations, over-flipped regions underestimated k PL and under-flipped regions overestimated k PL . B 1 + correction addressed this issue., Conclusion: The new HP 13 C EPSI post-processing pipeline integrated tensor denoising and B 1 + correction to measure k PL in patients with liver tumors. These technical developments not only recovered metabolite signals in voxels that did not receive the prescribed flip angle, but also increased the extent and accuracy of k PL estimations throughout the tumor and adjacent regions including normal-appearing tissue and additional lesions., (© 2021 International Society for Magnetic Resonance in Medicine.)

Background: MR enterography (MRE) is generally performed without bowel preparation, but the frequency and extent by which bowel contents affect bowel wall visualization are poorly described in the literature., Purpose: To evaluate MRE bowel wall visualization quality relative to bowel lumen contents and patient demographics., Study Type: Retrospective, single-center., Population: One hundred and four consecutive patients (mean age 29 years, range 5-76 years) without prior bowel resection who had undergone MRE., Field Strength/sequence: 3 T (N = 87) or 1.5 T (N = 17)/T2-weighted single-shot spin echo (T2WI) and fat-saturated T1-weighted gradient echo (T1WI) without and with gadolinium., Assessment: For the proximal and distal jejunum and ileum and colon, three readers independently categorized bowel lumen signal (water = bright T2 dark T1, T1-bright, or air = dark T2 and T1 signal) and scored distension (0 = poor, 1 = moderate, 2 = well) and wall enhancement (0 = unclear, 1 = perceptible, 2 = clear) based upon gadolinium enhanced T1WI for the 104 MRE exams). The bowel visualization score was the sum of the wall enhancement and distension scores and was considered adequate if ≥3., Statistical Tests: Wilcoxon signed-rank test., Results: The bowel lumen content was water signal in 93% (97/104 scans), 92% (95/104), 98% (102/104), and 93% (92/104) of the proximal and distal jejunum and proximal and distal ileum, respectively, but only in 12.5% (13/104) of the colon. There was adequate bowel visualization of 53.8%, 77.8%, 84.6%, 90.4% of the proximal and distal jejunum and proximal and distal ileum, respectively, but only 19.2% of the colon. In children (age < 18 years), the visualization score of the ileum was lower when the adjacent colon contained air (2.4 ± 0.97) compared to water (3.75 ± 0.29, P < 0.05) or T1-bright material (3.21 ± 0.82, P < 0.05)., Data Conclusion: Without bowel preparation, colon wall visualization was often unsatisfactory at MRE, and air-filled colon also degraded small bowel visualization, particularly in children., Level of Evidence: 4 TECHNICAL EFFICACY: Stage 1., (© 2021 International Society for Magnetic Resonance in Medicine.)

Purpose: To use fiducial markers containing manganese 55 to rapidly localize carbon 13 ( 13 C) RF coils for correcting images for B 1 variation., Methods: Hollow high-density polyethylene spheres were filled with 3M sodium permanganate and affixed to a rectangular 13 C-tuned RF coil. The relative positions of the markers and coil conductors were mapped using CT. Marker positions were measured by MRI using a series of 1D projections and automated peak detection. Once the coil location was determined, coil sensitivity was estimated using a quasi-static calculation. Simulations were performed to determine the minimum number of projections required for robust localization. Phantom experiments were used to confirm the accuracy of marker localization as well as the calculated coil sensitivity. Finally, in vivo validation was performed using hyperpolarized 13 C pyruvate in a rat model., Results: In simulations, our algorithm was accurate in determining marker positions when at least 6 projections were used (RMSE 1.4 ± 0.9 mm). These estimates were verified in phantom experiments, where markers locations were determined with an RMS accuracy of 1.3 mm. A minimum SNR of 4 was required for automated detection to perform accurately. Computed coil sensitivity had a median error of 17% when taken over the entire measured area and 5.7% over a central region. In a rat, correction for nonuniform reception and flip angle was able to normalize the signals arising from asymmetrically positioned kidneys., Conclusion: Manganese 55 fiducial markers are an inexpensive and reliable method for rapidly localizing 13 C RF coils and correcting 13 C images for B 1 variation without user intervention., (© 2020 International Society for Magnetic Resonance in Medicine.)

Background: Hyperpolarized (HP) 13 C-pyruvate MRI is a stable-isotope molecular imaging modality that provides real-time assessment of the rate of metabolism through glycolytic pathways in human prostate cancer. Heretofore this imaging modality has been successfully utilized in prostate cancer only in localized disease. This pilot clinical study investigated the feasibility and imaging performance of HP 13 C-pyruvate MR metabolic imaging in prostate cancer patients with metastases to the bone and/or viscera., Methods: Six patients who had metastatic castration-resistant prostate cancer were recruited. Carbon-13 MR examination were conducted on a clinical 3T MRI following injection of 250 mM hyperpolarized 13 C-pyruvate, where pyruvate-to-lactate conversion rate (k PL ) was calculated. Paired metastatic tumor biopsy was performed with histopathological and RNA-seq analyses., Results: We observed a high rate of glycolytic metabolism in prostate cancer metastases, with a mean k PL value of 0.020 ± 0.006 (s -1 ) and 0.026 ± 0.000 (s -1 ) in bone (N = 4) and liver (N = 2) metastases, respectively. Overall, high k PL showed concordance with biopsy-confirmed high-grade prostate cancer including neuroendocrine differentiation in one case. Interval decrease of k PL from 0.026 at baseline to 0.015 (s -1 ) was observed in a liver metastasis 2 months after the initiation of taxane plus platinum chemotherapy. RNA-seq found higher levels of the lactate dehydrogenase isoform A (Ldha,15.7 ± 0.7) expression relative to the dominant isoform of pyruvate dehydrogenase (Pdha1, 12.8 ± 0.9)., Conclusions: HP 13 C-pyruvate MRI can detect real-time glycolytic metabolism within prostate cancer metastases, and can measure changes in quantitative k PL values following treatment response at early time points. This first feasibility study supports future clinical studies of HP 13 C-pyruvate MRI in the setting of advanced prostate cancer.

This article discusses the 4 main imaging modalities used to evaluate reproductive-aged women: ultrasound, magnetic resonance imaging, computed tomography, and fluoroscopy. For each modality, major clinical indications are described, along with important technical considerations unique to imaging reproductive-aged women. Finally, key safety issues are discussed, particularly with regard to imaging pregnant patients., Competing Interests: Disclosure Dr Coutier is a consultant and shareholder in Sira Medical (augmented reality software company)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Placenta is a vital organ that connects the maternal and fetal circulations, allowing exchange of nutrients and gases between the two. In addition to the fetus, placenta is a key component to evaluate during any imaging performed during pregnancy. The most common disease processes involving the placenta include placenta accreta spectrum disorders and placental masses. Several systemic processes such as infection and fetal hydrops can too affect the placenta; however, their imaging features are nonspecific such as placental thickening, heterogeneity, and calcifications. Ultrasound is the first line of imaging during pregnancy, and MR imaging is reserved for problem solving, when there is need for higher anatomic resolution., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To evaluate correlation of "placental bulge sign" with myometrial invasion in placenta accreta spectrum (PAS) disorders. Placental bulge is defined as deviation of external uterine contour from expected plane caused by abnormal outward bulge of placental tissue., Materials and Methods: In this IRB-approved, retrospective study, all patients undergoing MRI for PAS disorders between March 2014 and 2018 were included. Patients who delivered elsewhere were excluded. Imaging was reviewed by 2 independent readers. Surgical pathology from Cesarean hysterectomy or pathology of the delivered placenta was used as reference standard. Fisher's exact and kappa tests were used for statistical analysis., Results: Sixty-one patients underwent MRI for PAS disorders. Two excluded patients delivered elsewhere. Placental bulge was present in 32 of 34 cases with myometrial invasion [True positive 32/34 = 94% (95% CI 0.80-0.99)]. Placental bulge was absent in 24 of 25 cases of normal placenta or placenta accreta without myometrial invasion [True negative = 24/25, 96% (95% CI 80-99.8%)]. Positive and negative predictive values were 97% and 96%, respectively. Placental bulge in conjunction with other findings of PAS disorder was 100% indicative of myometrial invasion (p < 0.01). Kappa value of 0.87 signified excellent inter-reader concordance. In 1 false positive, placenta itself was normal but the bulge was present. Surgical pathology revealed markedly thinned, fibrotic myometrium without accreta. One false-negative case was imaged at 16 weeks and may have been imaged too early., Conclusions: Placental bulge in conjunction with other findings of invasive placenta is 100% predictive of myometrial invasion. Using the bulge alone without other signs can lead to false-positive results.

Hyperpolarized (HP) carbon 13 ( 13 C) MRI is an emerging molecular imaging method that allows rapid, noninvasive, and pathway-specific investigation of dynamic metabolic and physiologic processes that were previously inaccessible to imaging. This technique has enabled real-time in vivo investigations of metabolism that are central to a variety of diseases, including cancer, cardiovascular disease, and metabolic diseases of the liver and kidney. This review provides an overview of the methods of hyperpolarization and 13 C probes investigated to date in preclinical models of disease. The article then discusses the progress that has been made in translating this technology for clinical investigation. In particular, the potential roles and emerging clinical applications of HP [1- 13 C]pyruvate MRI will be highlighted. The future directions to enable the adoption of this technology to advance the basic understanding of metabolism, to improve disease diagnosis, and to accelerate treatment assessment are also detailed., (©RSNA, 2019.)

Objective: The purpose of this study was to determine if extended PET acquisition times in the pelvis during PET/MRI increase detection rates of potentially metastatic lymph nodes in patients with rectal cancer., Materials and Methods: Our study was approved by the institutional review board of the University of California, San Francisco. Twenty-two patients with biopsy-proven rectal cancer underwent imaging via simultaneous 3-T time-of-flight PET/MRI, with seven undergoing two separate PET/MRI examinations, for a total of 29 studies. Each examination included both a whole-body PET/MRI and a dedicated pelvic PET/MRI with both 3- and 15-minute PET acquisitions for the pelvis. Three radiologists interpreted each examination with PET only, MRI only, then combined PET and MRI examinations, using all available images. Additionally, the 3- and 15-minute PET acquisitions of the pelvis were reviewed separately by a single radiologist., Results: A total of 94 lymph nodes were identified as abnormal on PET, all with MRI anatomic correlates. Of these, 37 (39.4%) were seen only on the dedicated 15-minute acquisition. Fifty-seven (60.6%) nodes measured 5 mm or less, including 29 (30.9%) seen only on the 15-minute acquisition. Thirty-one (33.0%) nodes measured 5.1-10 mm, including eight (25.8%) seen only on the 15-minute acquisition. Of the 17 subjects imaged for initial staging, 11 (64.7%) were upstaged as a result of the increased PET acquisition time (10 from N1 to N2 and one from N0 to N1)., Conclusion: Longer PET acquisition times during PET/MRI for rectal cancer increases the number of FDG-avid lymph nodes detected without increasing scan time.

Purpose: Although 1 H spin coupling is generally avoided in probes for hyperpolarized (HP) 13 C MRI, enzymatic transformations of biological interest can introduce large 13 C- 1 H couplings in vivo. The purpose of this study was to develop and investigate the application of 1 H decoupling for enhancing the sensitivity for detection of affected HP 13 C metabolic products., Methods: A standalone 1 H decoupler system and custom concentric 13 C/ 1 H paddle coil setup were integrated with a clinical 3T MRI scanner for in vivo 13 C MR studies using HP [2- 13 C]dihydroxyacetone, a novel sensor of hepatic energy status. Major 13 C- 1 H coupling J CH  = ∼150 Hz) is introduced after adenosine triphosphate-dependent enzymatic transformation of HP [2- 13 C]dihydroxyacetone to [2- 13 C]glycerol-3-phosphate in vivo. Application of WALTZ-16 1 H decoupling for elimination of large 13 C- 1 H couplings was first tested in thermally polarized glycerol phantoms and then for in vivo HP MR studies in three rats, scanned both with and without decoupling., Results: As configured, 1 H-decoupled 13 C MR of thermally polarized glycerol and the HP metabolic product [2- 13 C]glycerol-3-phosphate was achieved at forward power of approximately 15 W. High-quality 3-s dynamic in vivo HP 13 C MR scans were acquired with decoupling duty cycle of 5%. Application of 1 H decoupling resulted in sensitivity enhancement of 1.7-fold for detection of metabolic conversion of [2- 13 C]dihydroxyacetone to HP [2- 13 C]glycerol-3-phosphate in vivo., Conclusions: Application of 1 H decoupling provides significant sensitivity enhancement for detection of HP 13 C metabolic products with large 1 H spin couplings, and is therefore expected to be useful for preclinical and potentially clinical HP 13 C MR studies. Magn Reson Med 80:36-41, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: To evaluate acquisition time and clinical image quality of a variable refocusing flip angle (vrf) single-shot fast spin echo (SSFSE) sequence in comparison with a conventional SSFSE sequence for imaging of liver lesions in patients undergoing whole-body PET/MRI for oncologic staging., Methods: A vrfSSFSE sequence was acquired in 43 patients with known pancreatic neuroendocrine tumors undergoing 68 Ga-DOTA-TOC PET on a simultaneous time-of-flight 3.0T PET/MRI. Liver lesions ≥1.5 cm with radionucleotide uptake were analyzed. Contrast-to-noise ratios (CNRs) were measured, and four blinded radiologists assessed overall image quality. Differences in repetition time and CNR were assessed using a paired Student's t test with p < 0.05 considered statistically significant. Inter-reader variability was assessed with Fleiss' kappa statistic., Results: 53 eligible lesions in 27 patients were included for analysis. vrfSSFSE demonstrated higher mean lesion CNR compared to SSFSE (9.9 ± 4.1 vs. 6.7 ± 4.1, p < 0.001). Mean repetition time (TR) was 679 ± 97 ms for the vrfSSFSE sequence compared to 1139 ± 106 ms for SSFSE (p < 0.0001), corresponding to a 1.7-fold decrease in acquisition time. Overall quality of liver lesion and common bile duct images with the vrfSSFSE sequence was graded as superior than or equivalent to the SSFSE sequence for 59% and 67% of patients, respectively., Conclusions: Compared to conventional SSFSE, vrfSSFSE resulted in improved lesion contrast on simultaneous PET/MRI in patients with liver metastases. Due to decreased SAR demands, vrfSSFSE significantly decreased TR, allowing coverage of the entire liver in a single twenty-second breath hold. This may have important clinical implications in the setting of PET/MRI, where scan time is limited by the necessity of whole-body image acquisition in addition to bed specific imaging.

The type 2 diabetic phenotype results from mixed effects of insulin deficiency and insulin resistance, but the relative contributions of these two distinct factors remain poorly characterized, as do the respective roles of the gluconeogenic organs. The purpose of this study was to investigate localized in vivo metabolic changes in liver and kidneys of contrasting models of diabetes mellitus (DM): streptozotocin (STZ)-treated wild-type Zucker rats (T1DM) and Zucker diabetic fatty (ZDF) rats (T2DM). Intermediary metabolism was probed using hyperpolarized (HP) [1- 13 C]pyruvate MRI of the liver and kidneys. These data were correlated with gene expression data for key mediators, assessed using rtPCR. Increased HP [1- 13 C]lactate was detected in both models, in association with elevated gluconeogenesis as reflected by increased expression of phosphoenolpyruvate carboxykinase. In contrast, HP [1- 13 C]alanine diverged between the two models, increasing in ZDF rats, while decreasing in the STZ-treated rats. The differences in liver alanine paralleled differences in key lipogenic mediators. Thus, HP [1- 13 C]alanine is a marker that can identify phenotypic differences in kidneys and liver of rats with T1DM vs. T2DM, non-invasively in vivo. This approach could provide a powerful diagnostic tool for characterizing tissue metabolic defects and responses to treatment in diabetic patients with ambiguous systemic manifestations.

The Liver Imaging Reporting and Data System (LI-RADS) standardizes the interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). It assigns category codes reflecting relative probability of HCC to imaging-detected liver observations based on major and ancillary imaging features. LI-RADS also includes imaging features suggesting malignancy other than HCC. Supported and endorsed by the American College of Radiology (ACR), the system has been developed by a committee of radiologists, hepatologists, pathologists, surgeons, lexicon experts, and ACR staff, with input from the American Association for the Study of Liver Diseases and the Organ Procurement Transplantation Network/United Network for Organ Sharing. Development of LI-RADS has been based on literature review, expert opinion, rounds of testing and iteration, and feedback from users. This article summarizes and assesses the quality of evidence supporting each LI-RADS major feature for diagnosis of HCC, as well as of the LI-RADS imaging features suggesting malignancy other than HCC. Based on the evidence, recommendations are provided for or against their continued inclusion in LI-RADS. © RSNA, 2017 Online supplemental material is available for this article.

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., (© 2016 International Society for Magnetic Resonance in Medicine.)

MR imaging and PET using 2-Deoxy-2-[ 18 F]fluoroglucose (FDG) are both useful in the evaluation of gynecologic malignancies. MR imaging is superior for local staging of disease whereas fludeoxyglucose FDG PET is superior for detecting distant metastases. Integrated PET/MR imaging scanners have great promise for gynecologic malignancies by combining the advantages of each modality into a single scan. This article reviews the technology behind PET/MR imaging acquisitions and technical challenges relevant to imaging the pelvis. A dedicated PET/MR imaging protocol; the roles of PET and MR imaging in cervical, endometrial, and ovarian cancers; and future directions for PET/MR imaging are discussed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Hyperpolarized 13 C MRI is a powerful tool for studying metabolism, but can lack tissue specificity. Gadoxetate is a gadolinium-based MRI contrast agent that is selectively taken into hepatocytes. The goal of this project was to investigate whether gadoxetate can be used to selectively suppress the hyperpolarized signal arising from hepatocytes, which could in future studies be applied to generate specificity for signal from abnormal cell types., Methods: Baseline gadoxetate uptake kinetics were measured using T 1 -weighted contrast enhanced imaging. Relaxivity of gadoxetate was measured for [1- 13 C]pyruvate, [1- 13 C]lactate, and [1- 13 C]alanine. Four healthy rats were imaged with hyperpolarized [1- 13 C]pyruvate using a three-dimensional (3D) MRSI sequence prior to and 15 min following administration of gadoxetate. The lactate:pyruvate ratio and alanine:pyruvate ratios were measured in liver and kidney., Results: Overall, the hyperpolarized signal decreased approximately 60% as a result of pre-injection of gadoxetate. In liver, the lactate:pyruvate and alanine:pyruvate ratios decreased 42% and 78%, respectively (P < 0.05) following gadoxetate administration. In kidneys, these ratios did not change significantly. Relaxivity of gadoxetate for [1- 13 C]alanine was 12.6 times higher than relaxivity of gadoxetate for [1- 13 C]pyruvate, explaining the greater selective relaxation effect on alanine., Conclusions: The liver-specific gadolinium contrast-agent gadoxetate can selectively suppress normal hepatocyte contributions to hyperpolarized 13 C MRI signals. Magn Reson Med 77:2356-2363, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: To evaluate the performance of diffusion-weighted imaging (DWI) and T2-weighted single shot fast spin-echo (SSFSE) imaging of the liver in the detection of hepatocellular carcinoma (HCC) in reference to the LI-RADS classification system., Methods: MR images of 40 patients with 68 LI-RADS grade 3-5 lesions were analyzed. Two readers independently reviewed sequences and characterized lesion signal intensity, followed by consensus evaluation. CE-MRI served as reference standard. Sensitivities were compared across sequences. Lesion-to-liver contrast-to-noise ratios (CNRs) and apparent diffusion coefficients (ADCs) were measured and compared using the Wilcoxon signed-rank test across sequences and the Mann-Whitney U or Kruskal-Wallis test between LI-RADS categories. Inter-reader variability was assessed using Cohen's kappa statistic., Results: Consensus sensitivities of LI-RADS 3-5 lesions using SSFSE images versus DWI were similar (0.53-0.63, p=0.089), however, the sensitivity with DWI b=700 was higher (0.63) than DWI b=0 (0.53, p=0.039). Lesion-to-liver CNRs were larger for all DWI sequences compared to SSFSE images (p<0.001 for all). ADCs of large (>2cm) LIRADS 3-5 lesions were lower than those of small lesions (1.09±0.33 vs. 1.31±0.26, p=0.02), however lesion ADCs were not different from those of adjacent hepatic parenchyma for any LI-RADS lesion., Conclusions: DWI has a similar sensitivity compared to SSFSE, but intensity on DWI likely represents intrinsic T2 signal hyper-intensity rather than restricted diffusion as the ADC values were not lower than adjacent parenchyma. Therefore it may not be appropriate to consider hyper-intensity on high b-value as a separate ancillary criteria to T2 hyper-intensity in LI-RADS., (Published by Elsevier Inc.)

Purpose: The purpose of this study was to investigate (13) C hyperpolarization of α-ketobutyrate (αKB), an endogenous molecular analog of pyruvate, and its in vivo enzymatic conversion via lactate dehydrogenase (LDH) using localized MR spectroscopy., Methods: Hyperpolarized (HP) (13) C MR experiments were conducted using [(13) C]αKB with rats in vivo and with isolated LDH enzyme in vitro, along with comparative experiments using [(13) C]pyruvate. Based on differences in the kinetics of its reaction with individual LDH isoforms, HP [(13) C]αKB was investigated as a novel MR probe, with added specificity for activity of LDHB-expressed H ("heart"-type) subunits of LDH (e.g., constituents of LDH-1 isoform)., Results: Comparable T1 and polarization values to pyruvate were attained (T1  = 52 s at 3 tesla [T], polarization = 10%, at C1 ). MR experiments showed rapid enzymatic conversion with substantially increased specificity. Formation of product HP [(13) C]α-hydroxybutyrate (αHB) from αKB in vivo was increased 2.7-fold in cardiac slabs relative to liver and kidney slabs. In vitro studies resulted in 5.0-fold higher product production from αKB with bovine heart LDH-1, as compared with pyruvate., Conclusions: HP [(13) C]αKB may be a useful MR probe of cardiac metabolism and other applications where the role of H subunits of LDH is significant (e.g., renal cortex and brain)., (© 2015 Wiley Periodicals, Inc.)

A calibrationless parallel imaging technique developed previously for (1)H MRI was modified and tested for hyperpolarized (13)C MRI for applications requiring large FOV and high spatial resolution. The technique was demonstrated with both retrospective and prospective under-sampled data acquired in phantom and in vivo rat studies. A 2-fold acceleration was achieved using a 2D symmetric EPI readout equipped with random blips on the phase encode dimension. Reconstructed images showed excellent qualitative agreement with fully sampled data. Further acceleration can be achieved using acquisition schemes that incorporate multi-dimensional under-sampling., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Selective RF pulses are commonly designed with the desired profile as a low pass filter frequency response. However, for many MRI and NMR applications, the spectrum is sparse with signals existing at a few discrete resonant frequencies. By specifying a multiband profile and releasing the constraint on "don't-care" regions, the RF pulse performance can be improved to enable a shorter duration, sharper transition, or lower peak B1 amplitude. In this project, a framework for designing multiband RF pulses with improved performance was developed based on the Shinnar-Le Roux (SLR) algorithm and convex optimization. It can create several types of RF pulses with multiband magnitude profiles, arbitrary phase profiles and generalized flip angles. The advantage of this framework with a convex optimization approach is the flexible trade-off of different pulse characteristics. Designs for specialized selective RF pulses for balanced SSFP hyperpolarized (HP) (13)C MRI, a dualband saturation RF pulse for (1)H MR spectroscopy, and a pre-saturation pulse for HP (13)C study were developed and tested., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (© 2014 Wiley Periodicals, Inc.)

Purpose: A calibrationless parallel imaging reconstruction method, termed simultaneous autocalibrating and k-space estimation (SAKE), is presented. It is a data-driven, coil-by-coil reconstruction method that does not require a separate calibration step for estimating coil sensitivity information., Methods: In SAKE, an undersampled, multichannel dataset is structured into a single data matrix. The reconstruction is then formulated as a structured low-rank matrix completion problem. An iterative solution that implements a projection-onto-sets algorithm with singular value thresholding is described., Results: Reconstruction results are demonstrated for retrospectively and prospectively undersampled, multichannel Cartesian data having no calibration signals. Additionally, non-Cartesian data reconstruction is presented. Finally, improved image quality is demonstrated by combining SAKE with wavelet-based compressed sensing., Conclusion: Because estimation of coil sensitivity information is not needed, the proposed method could potentially benefit MR applications where acquiring accurate calibration data is limiting or not possible at all., (Copyright © 2013 Wiley Periodicals, Inc.)

Over the past decade the role of MR imaging in the evaluation of diffuse liver disease has become common practice. Although detection of focal liver lesions remains the mainstay of liver imaging, a growing cohort of patients are referred for evaluation of hepatosteatosis, iron deposition diseases, and cirrhosis. In particular, multiecho sequences are becoming the gold standard for quantification of fat and iron. MR elastography allows for improved early detection of hepatic fibrosis. Unfortunately, a majority of the diffuse liver diseases lack specific features on MR imaging, yet a solid understanding of the different pathologic processes allows an informed interpretation., (Published by Elsevier Inc.)

The basic principles of radiofrequency coil array design for parallel MRI are described from both theoretical and practical perspectives. Because parallel MRI techniques rely on coil array sensitivities to provide spatial information about the sample, a careful choice of array design is essential. The concepts of coil array spatial encoding are first discussed from four qualitative perspectives. These qualitative descriptions include using coil arrays to emulate spatial harmonics, choosing coils with selective sensitivities to aliased pixels, using coil sensitivities with broad k-space reception profiles, and relying on detector coils to provide a set of generalized projections of the sample. This qualitative discussion is followed by a quantitative analysis of coil arrays, which is discussed in terms of the baseline SNR of the received images as well as the noise amplifications (g-factor) in the reconstructed data. The complications encountered during the experimental evaluation of coil array SNR are discussed, and solutions are proposed. A series of specific array designs are reviewed, with an emphasis on the general design considerations that motivate each approach. Finally, a set of special topics is discussed, which reflect issues that have become important, especially as arrays are being designed for more high-performance applications of parallel MRI. These topics include concerns about the depth penetration of arrays composed of small elements, the use of adaptive arrays for systems with limited receiver channels, the management of inductive coupling between array elements, and special considerations required at high field strengths. The fundamental limits of spatial encoding using coil arrays are discussed, with a primary emphasis on how the determination of these limits impacts the design of optimized arrays. This review is intended to provide insight into how arrays are currently used for parallel MRI and to place into context the new innovations that are to come., (Copyright (c) 2006 John Wiley & Sons, Ltd.)

A new type of coil array is proposed that consists of concentrically placed coil elements, each of which is characterized by symmetrically arranged lobes that have alternating current directions. Symmetries in the coil elements' conductor paths allow for the minimization of mutual inductance and noise correlations. In addition, the concentric arrangement of the coil elements provides spatial encoding capabilities in multiple directions, which is valuable when arrays are used with parallel MRI. Simulations are presented that describe the signal-to-noise ratio (SNR) properties of individual concentric array elements, and a four-element prototype concentric array is constructed. This prototype array is compared experimentally with three alternative four-element array designs. The overall SNR of the concentric array is comparable to the SNR of the competing arrays. Reconstruction of twofold undersampled data using the concentric array yields an average g-factor of less than 1.3 in all directions parallel to the plane of the array. There is some degradation in performance when threefold undersampled data are reconstructed, but the array still shows substantial directional invariance compared to alternative designs. Both fully-sampled and undersampled cardiac images acquired using the concentric array are shown. These results suggest that concentric structures can be useful tools for designing specialized coil arrays for parallel MRI., ((c) 2005 Wiley-Liss, Inc.)

A generalized method for phase-constrained parallel MR image reconstruction is presented that combines and extends the concepts of partial-Fourier reconstruction and parallel imaging. It provides a framework for reconstructing images employing either or both techniques and for comparing image quality achieved by varying k-space sampling schemes. The method can be used as a parallel image reconstruction with a partial-Fourier reconstruction built in. It can also be used with trajectories not readily handled by straightforward combinations of partial-Fourier and SENSE-like parallel reconstructions, including variable-density, and non-Cartesian trajectories. The phase constraint specifies a better-conditioned inverse problem compared to unconstrained parallel MR reconstruction alone. This phase-constrained parallel MRI reconstruction offers a one-step alternative to the standard combination of homodyne and SENSE reconstructions with the added benefit of flexibility of sampling trajectory. The theory of the phase-constrained approach is outlined, and its calibration requirements and limitations are discussed. Simulations, phantom experiments, and in vivo experiments are presented.

A parallel image reconstruction algorithm is presented that exploits the k-space locality in radiofrequency (RF) coil encoded data. In RF coil encoding, information relevant to reconstructing an omitted datum rapidly diminishes as a function of k-space separation between the omitted datum and the acquired signal data. The proposed method, parallel magnetic resonance imaging with adaptive radius in k-space (PARS), harnesses this physical property of RF coil encoding via a sliding-kernel approach. Unlike generalized parallel imaging approaches that might typically involve inverting a prohibitively large matrix for arbitrary sampling trajectories, the PARS sliding-kernel approach creates manageable and distributable independent matrices to be inverted, achieving both computational efficiency and numerical stability. An empirical method designed to measure total error power is described, and the total error power of PARS reconstructions is studied over a range of k-space radii and accelerations, revealing "minimal-error" conditions at comparatively modest k-space radii. PARS reconstructions of undersampled in vivo Cartesian and non-Cartesian data sets are shown and are compared selectively with traditional SENSE reconstructions. Various characteristics of the PARS k-space locality constraint (such as the tradeoff between signal-to-noise ratio and artifact power and the relationship with iterative parallel conjugate gradient approaches or nonparallel gridding approaches) are discussed.

Rationale and Objectives: Many clinical applications of Magnetic Resonance Imaging are constrained by basic limits on imaging speed. Parallel MRI relaxes these limits by using the sensitivity patterns of arrays of radiofrequency receiver coils to encode spatial information in a manner complementary to traditional encoding with magnetic field gradients. Until now, parallel MRI has been used to achieve modest improvements in imaging speed; order-of-magnitude improvements have been elusive given fundamental losses in signal-to-noise ratio. The goal of this work was to demonstrate that, with appropriate hardware and careful SNR management, rapid volumetric imaging at high accelerations is in fact feasible., Materials and Methods: Contrast-enhanced MRI with an axial 3D spoiled gradient echo imaging sequence was performed in healthy adult subjects using a 32-element RF coil array and a prototype 32-channel MR imaging system. Large imaging volumes were prescribed, in place of traditional limited slabs targeted only to suspect regions., Results: As much as 16-fold net accelerations of imaging were achieved repeatably using this approach. The use of large 3D volumes allowed comprehensive anatomical coverage at clinically useful spatial and/or temporal resolution. The need for careful, time-consuming, and subject-specific scan prescription was also eliminated., Conclusion: The highly parallel imaging approach presented here allows previously inaccessible volumetric coverage for time-sensitive MRI examinations such as contrast-enhanced MRA, and simultaneously provides a substantially simplified imaging paradigm. The resulting capability for rapid volumetric imaging promises to combine the strengths of MRI with some of the advantages of alternative imaging modalities such as multidetector CT.

The improvement of MRI speed with parallel acquisition is ultimately an SNR-limited process. To offset acquisition- and reconstruction-related SNR losses, practical parallel imaging at high accelerations should include the use of a many-element array with a high intrinsic signal-to-noise ratio (SNR) and spatial-encoding capability, and an advantageous imaging paradigm. We present a 32-element receive-coil array and a volumetric paradigm that address the SNR challenge at high accelerations by maximally exploiting multidimensional acceleration in conjunction with noise averaging. Geometric details beyond an initial design concept for the array were determined with the guidance of simulations. Imaging with the support of 32-channel data acquisition systems produced in vivo results with up to 16-fold acceleration, including images from rapid abdominal and MRA studies.

Theoretical arguments and experimental results are presented that characterize the impact of inductive coupling on the performance of parallel MRI reconstructions. A simple model of MR signal and noise reception suggests that the intrinsic amount of spatial information available from a given coil array is unchanged in the presence of inductive coupling, as long as the sample remains the dominant source of noise for the coupled array. Any loss of distinctness in the measured coil sensitivities is compensated by information stored in the measured noise correlations. Adjustments to the theory are described to account for preamplifier noise contributions. Results are presented from an experimental system in which preamplifier input impedances are systematically adjusted in order to vary the level of coupling between array elements. Parallel image reconstructions using an array with four different levels of coupling and an acceleration factor up to six show average SNR changes of -7.6% to +7.5%. The modest changes in overall SNR are accompanied by similarly small changes in g-factor. These initial results suggest that moderate amounts of inductive coupling should not have a prohibitive effect on the use of a given coil array for parallel MRI., (Copyright 2004 Wiley-Liss, Inc.)

A method is described for establishing an upper bound on the spatial encoding capabilities of coil arrays in parallel MRI. Ultimate intrinsic signal-to-noise ratio (SNR), independent of any particular conductor arrangement, is calculated by expressing arbitrary coil sensitivities in terms of a complete set of basis functions that satisfy Maxwell's equations within the sample and performing parallel imaging reconstructions using these basis functions. The dependence of the ultimate intrinsic SNR on a variety of experimental conditions is explored and a physically intuitive explanation for the observed behavior is provided based on a comparison between the electromagnetic wavelength and the distance between aliasing points. Imaging at high field strength, with correspondingly short wavelength, is shown to offer advantages for parallel imaging beyond those already expected due to the larger available spin polarization. One-dimensional undersampling of k-space yields a steep drop in attainable SNR for more than a 5-fold reduction of scan time, while 2D undersampling permits access to much higher degrees of acceleration. Increased tissue conductivity decreases baseline SNR, but improves parallel imaging performance. A procedure is also provided for generating the optimal coil sensitivity pattern for a given acceleration, which will serve as a useful guide for future coil designs., (Copyright 2003 Wiley-Liss, Inc.)

Calibration of the spatial sensitivity functions of coil arrays is a crucial element in parallel magnetic resonance imaging (PMRI). The most common approach has been to measure coil sensitivities directly using one or more low-resolution images acquired before or after accelerated data acquisition. However, since it is difficult to ensure that the patient and coil array will be in exactly the same positions during both calibration scans and accelerated imaging, this approach can introduce sensitivity miscalibration errors into PMRI reconstructions. This work shows that it is possible to extract sensitivity calibration images directly from a fully sampled central region of a variable-density k-space acquisition. These images have all the features of traditional PMRI sensitivity calibrations and therefore may be used for any PMRI reconstruction technique without modification. Because these calibration data are acquired simultaneously with the data to be reconstructed, errors due to sensitivity miscalibration are eliminated. In vivo implementations of self-calibrating parallel imaging using a flexible coil array are demonstrated in abdominal imaging and in real-time cardiac imaging studies., (Copyright 2002 Wiley-Liss, Inc.)

Parallel magnetic resonance imaging (MRI) techniques use spatial information from arrays of radiofrequency (RF) detector coils to accelerate imaging. A number of parallel MRI techniques have been described in recent years, and numerous clinical applications are currently being explored. The advent of practical parallel imaging presents various challenges for image reconstruction and RF system design. Recent advances in tailored SiMultaneous Acquisition of Spatial Harmonics (SMASH) image reconstructions are summarized. These advances enable robust SMASH imaging in arbitrary image planes with a wide range of coil array geometries. A generalized formalism is described which may be used to understand the relations between SMASH and SENSE, to derive typical implementations of each as special cases, and to form hybrid techniques combining some of the advantages of both. Accurate knowledge of coil sensitivities is crucial for parallel MRI, and errors in calibration represent one of the most common and the most pernicious sources of error in parallel image reconstructions. As one example, motion of the patient and/or the coil array between the sensitivity reference scan and the accelerated acquisition can lead to calibration errors and reconstruction artifacts. Self-calibrating parallel MRI approaches that address this problem by eliminating the need for external sensitivity references are reviewed. The ultimate achievable signal-to-noise ratio (SNR) for parallel MRI studies is closely tied to the geometry and sensitivity patterns of the coil arrays used for spatial encoding. Several parallel imaging array designs that depart from the traditional model of overlapped adjacent loop elements are described.

We aimed to characterize scenarios where magnetic resonance elastography (MRE) of the liver was ordered and its impact on clinical course and management. 96 consecutive MRE examinations and subsequent encounters over 14 months were reviewed. Indication for MRE of the liver and subsequent management were abstracted from the medical record. In all cases, non-invasive assessment of liver fibrosis was the primary indication and at least one additional rationale was noted. There was a significant decrease in recommendations to undergo liver biopsy after MRE. Additionally, a greater percentage of those recommended to undergo biopsy completed the procedure after discussion of the results. Given the significant cost and rare but serious risks of liver biopsy, MRE of the liver provides an attractive, safer alternative that may have a comparable impact on management, or select cases where biopsy is essential to guide management. We demonstrate the versatility of MRE in real-world hepatology practice, including its utility as a non-invasive surrogate for liver biopsy.

Background Various limitations have impacted research evaluating reader agreement for Liver Imaging Reporting and Data System (LI-RADS). Purpose To assess reader agreement of LI-RADS in an international multicenter multireader setting using scrollable images. Materials and Methods This retrospective study used deidentified clinical multiphase CT and MRI and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 to August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS version 2018 category was computed as a rescored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1, definitely benign; LR-2, probably benign; LR-3, intermediate probability of malignancy; LR-4, probably hepatocellular carcinoma [HCC]; LR-5, definitely HCC; LR-M, probably malignant but not HCC specific; and LR-TIV, tumor in vein) was computed using intraclass correlation coefficients (ICCs). Agreement was also computed for dichotomized malignancy (LR-4, LR-5, LR-M, and LR-TIV), LR-5, and LR-M. Agreement was compared between research-versus-research reads and research-versus-clinical reads. Results The study population consisted of 484 patients (mean age, 62 years ± 10 [SD]; 156 women; 93 CT examinations, 391 MRI examinations). ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.61, 0.73), 0.63 (95% CI: 0.55, 0.70), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs 0.62, respectively; P = .03) and for dichotomized malignancy (ICC, 0.63 vs 0.53, respectively; P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion There was moderate agreement for LI-RADS version 2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study. © RSNA, 2023 Supplemental material is available for this article. See also the editorials by Johnson and Galgano and Smith in this issue.

Background & aimsNon-alcoholic steatohepatitis (NASH) is prevalent in adults with obesity and can progress to cirrhosis. In a secondary analysis of prospectively acquired data from the multicenter, randomized, placebo-controlled FLINT trial, we investigated the relationship between reduction in adipose tissue compartment volumes and hepatic histologic improvement.MethodsAdult participants in the FLINT trial with paired liver biopsies and abdominal MRI exams at baseline and end-of-treatment (72 weeks) were included (n = 76). Adipose tissue compartment volumes were obtained using MRI.ResultsTreatment and placebo groups did not differ in baseline adipose tissue volumes, or in change in adipose tissue volumes longitudinally (p = 0.107 to 0.745). Deep subcutaneous adipose tissue (dSAT) and visceral adipose tissue volume reductions were associated with histologic improvement in NASH (i.e., NAS [non-alcoholic fatty liver disease activity score] reductions of ≥2 points, at least 1 point from lobular inflammation and hepatocellular ballooning, and no worsening of fibrosis) (p = 0.031, and 0.030, respectively). In a stepwise logistic regression procedure, which included demographics, treatment group, baseline histology, baseline and changes in adipose tissue volumes, MRI hepatic proton density fat fraction (PDFF), and serum aminotransferases as potential predictors, reductions in dSAT and PDFF were associated with histologic improvement in NASH (regression coefficient = -2.001 and -0.083, p = 0.044 and 0.033, respectively).ConclusionsIn adults with NASH in the FLINT trial, those with greater longitudinal reductions in dSAT and potentially visceral adipose tissue volumes showed greater hepatic histologic improvements, independent of reductions in hepatic PDFF.Clinical trial numberNCT01265498.Impact and implicationsAlthough central obesity has been identified as a risk factor for obesity-related disorders including insulin resistance and cardiovascular disease, the role of central obesity in non-alcoholic steatohepatitis (NASH) warrants further clarification. Our results highlight that a reduction in central obesity, specifically deep subcutaneous adipose tissue and visceral adipose tissue, may be related to histologic improvement in NASH. The findings from this analysis should increase awareness of the importance of lifestyle intervention in NASH for clinical researchers and clinicians. Future studies and clinical practice may design interventions that assess the reduction of deep subcutaneous adipose tissue and visceral adipose tissue as outcome measures, rather than simply weight reduction.

BackgroundHyperpolarized 13 C MRI quantitatively measures enzyme-catalyzed metabolism in cancer and metabolic diseases. Whole-abdomen imaging will permit dynamic metabolic imaging of several abdominal organs simultaneously in healthy and diseased subjects.PurposeImage hyperpolarized [1-13 C]pyruvate and products in the abdomens of healthy volunteers, overcoming challenges of motion, magnetic field variations, and spatial coverage. Compare hyperpolarized [1-13 C]pyruvate metabolism across abdominal organs of healthy volunteers.Study typeProspective technical development.SubjectsA total of 13 healthy volunteers (8 male), 21-64 years (median 36).Field strength/sequenceA 3 T. Proton: T1 -weighted spoiled gradient echo, T2 -weighted single-shot fast spin echo, multiecho fat/water imaging. Carbon-13: echo-planar spectroscopic imaging, metabolite-specific echo-planar imaging.AssessmentTransmit magnetic field was measured. Variations in main magnetic field (ΔB0 ) determined using multiecho proton acquisitions were compared to carbon-13 acquisitions. Changes in ΔB0 were measured after localized shimming. Improvements in metabolite signal-to-noise ratio were calculated. Whole-organ regions of interests were drawn over the liver, spleen, pancreas, and kidneys by a single investigator. Metabolite signals, time-to-peak, decay times, and mean first-order rate constants for pyruvate-to-lactate (kPL ) and alanine (kPA ) conversion were measured in each organ.Statistical testsLinear regression, one-sample Kolmogorov-Smirnov tests, paired t-tests, one-way ANOVA, Tukey's multiple comparisons tests. P ≤ 0.05 considered statistically significant.ResultsProton ΔB0 maps correlated with carbon-13 ΔB0 maps (slope = 0.93, y-intercept = -2.88, R2  = 0.73). Localized shimming resulted in mean frequency offset within ±25 Hz for all organs. Metabolite SNR significantly increased after denoising. Mean kPL and kPA were highest in liver, followed by pancreas, spleen, and kidneys (all comparisons with liver were significant).Data conclusionWhole-abdomen coverage with hyperpolarized carbon-13 MRI was feasible despite technical challenges. Multiecho gradient echo 1 H acquisitions accurately predicted chemical shifts observed using carbon-13 spectroscopy. Carbon-13 acquisitions benefited from local shimming. Metabolite energetics in the abdomen compiled for healthy volunteers can be used to design larger clinical trials in patients with metabolic diseases.Evidence level2 TECHNICAL EFFICACY: Stage 1.

PurposeTo develop techniques and establish a workflow using hyperpolarized carbon-13 (13 C) MRI and the pyruvate-to-lactate conversion rate (kPL ) biomarker to guide MR-transrectal ultrasound fusion prostate biopsies.MethodsThe integrated multiparametric MRI (mpMRI) exam consisted of a 1-min hyperpolarized 13 C-pyruvate EPI acquisition added to a conventional prostate mpMRI exam. Maps of kPL values were calculated, uploaded to a picture archiving and communication system and targeting platform, and displayed as color overlays on T2 -weighted anatomic images. Abdominal radiologists identified 13 C research biopsy targets based on the general recommendation of focal lesions with kPL  >0.02(s-1 ), and created a targeting report for each study. Urologists conducted transrectal ultrasound-guided MR fusion biopsies, including the standard 1 H-mpMRI targets as well as 12-14 core systematic biopsies informed by the research 13 C-kPL targets. All biopsy results were included in the final pathology report and calculated toward clinical risk.ResultsThis study demonstrated the safety and technical feasibility of integrating hyperpolarized 13 C metabolic targeting into routine 1 H-mpMRI and transrectal ultrasound fusion biopsy workflows, evaluated via 5 men (median age 71 years, prostate-specific antigen 8.4 ng/mL, Cancer of the Prostate Risk Assessment score 2) on active surveillance undergoing integrated scan and subsequent biopsies. No adverse event was reported. Median turnaround time was less than 3 days from scan to 13 C-kPL targeting, and scan-to-biopsy time was 2 weeks. Median number of 13 C targets was 1 (range: 1-2) per patient, measuring 1.0 cm (range: 0.6-1.9) in diameter, with a median kPL of 0.0319 s-1 (range: 0.0198-0.0410).ConclusionsThis proof-of-concept work demonstrated the safety and feasibility of integrating hyperpolarized 13 C MR biomarkers to the standard mpMRI workflow to guide MR-transrectal ultrasound fusion biopsies.

PurposeNon-invasive imaging is a key clinical tool for detection and treatment monitoring of infections. Existing clinical imaging techniques are frequently unable to distinguish infection from tumors or sterile inflammation. This challenge is well-illustrated by prosthetic joint infections that often complicate joint replacements. D-methyl-11C-methionine (D-11C-Met) is a new bacteria-specific PET radiotracer, based on an amino acid D-enantiomer, that is rapidly incorporated into the bacterial cell wall. In this manuscript, we describe the biodistribution, radiation dosimetry, and initial human experience using D-11C-Met in patients with suspected prosthetic joint infections.Methods614.5 ± 100.2 MBq of D-11C-Met was synthesized using an automated in-loop radiosynthesis method and administered to six healthy volunteers and five patients with suspected prosthetic joint infection, who were studied by PET/MRI. Time-activity curves were used to calculate residence times for each source organ. Absorbed doses to each organ and body effective doses were calculated using OLINDA/EXM 1.1 with both ICRP 60 and ICRP 103 tissue weighting factors. SUVmax and SUVpeak were calculated for volumes of interest (VOIs) in joints with suspected infection, the unaffected contralateral joint, blood pool, and soft tissue background. A two-tissue compartment model was used for kinetic modeling.ResultsD-11C-Met was well tolerated in all subjects. The tracer showed clearance from both urinary (rapid) and hepatobiliary (slow) pathways as well as low effective doses. Moreover, minimal background was observed in both organs with resident micro-flora and target organs, such as the spine and musculoskeletal system. Additionally, D-11C-Met showed increased focal uptake in areas of suspected infection, demonstrated by a significantly higher SUVmax and SUVpeak calculated from VOIs of joints with suspected infections compared to the contralateral joints, blood pool, and background (P

PurposeTo develop a novel post-processing pipeline for hyperpolarized (HP) 13 C MRSI that integrates tensor denoising and B1+ correction to measure pyruvate-to-lactate conversion rates (kPL ) in patients with liver tumors.MethodsSeven HP 13 C MR scans of progressing liver tumors were acquired using a custom 13 C surface transmit/receive coil and the echo-planar spectroscopic imaging (EPSI) data analysis included B0 correction, tensor rank truncation, and zero- and first-order phase corrections to recover metabolite signals that would otherwise be obscured by spectral noise as well as a correction for inhomogeneous transmit ( B1+ ) using a B1+ map aligned to the coil position for each patient scan. Processed HP data and corrected flip angles were analyzed with an inputless two-site exchange model to calculate kPL .ResultsDenoising averages SNR increases of pyruvate, lactate, and alanine were 37.4-, 34.0-, and 20.1-fold, respectively, with lactate and alanine dynamics most noticeably recovered and better defined. In agreement with Monte Carlo simulations, over-flipped regions underestimated kPL and under-flipped regions overestimated kPL . B1+ correction addressed this issue.ConclusionThe new HP 13 C EPSI post-processing pipeline integrated tensor denoising and B1+ correction to measure kPL in patients with liver tumors. These technical developments not only recovered metabolite signals in voxels that did not receive the prescribed flip angle, but also increased the extent and accuracy of kPL estimations throughout the tumor and adjacent regions including normal-appearing tissue and additional lesions.

PurposeTo use fiducial markers containing manganese 55 to rapidly localize carbon 13 (13 C) RF coils for correcting images for B1 variation.MethodsHollow high-density polyethylene spheres were filled with 3M sodium permanganate and affixed to a rectangular 13 C-tuned RF coil. The relative positions of the markers and coil conductors were mapped using CT. Marker positions were measured by MRI using a series of 1D projections and automated peak detection. Once the coil location was determined, coil sensitivity was estimated using a quasi-static calculation. Simulations were performed to determine the minimum number of projections required for robust localization. Phantom experiments were used to confirm the accuracy of marker localization as well as the calculated coil sensitivity. Finally, in vivo validation was performed using hyperpolarized 13 C pyruvate in a rat model.ResultsIn simulations, our algorithm was accurate in determining marker positions when at least 6 projections were used (RMSE 1.4 ± 0.9 mm). These estimates were verified in phantom experiments, where markers locations were determined with an RMS accuracy of 1.3 mm. A minimum SNR of 4 was required for automated detection to perform accurately. Computed coil sensitivity had a median error of 17% when taken over the entire measured area and 5.7% over a central region. In a rat, correction for nonuniform reception and flip angle was able to normalize the signals arising from asymmetrically positioned kidneys.ConclusionManganese 55 fiducial markers are an inexpensive and reliable method for rapidly localizing 13 C RF coils and correcting 13 C images for B1 variation without user intervention.

BackgroundHyperpolarized (HP) 13C-pyruvate MRI is a stable-isotope molecular imaging modality that provides real-time assessment of the rate of metabolism through glycolytic pathways in human prostate cancer. Heretofore this imaging modality has been successfully utilized in prostate cancer only in localized disease. This pilot clinical study investigated the feasibility and imaging performance of HP 13C-pyruvate MR metabolic imaging in prostate cancer patients with metastases to the bone and/or viscera.MethodsSix patients who had metastatic castration-resistant prostate cancer were recruited. Carbon-13 MR examination were conducted on a clinical 3T MRI following injection of 250 mM hyperpolarized 13C-pyruvate, where pyruvate-to-lactate conversion rate (kPL) was calculated. Paired metastatic tumor biopsy was performed with histopathological and RNA-seq analyses.ResultsWe observed a high rate of glycolytic metabolism in prostate cancer metastases, with a mean kPL value of 0.020 ± 0.006 (s-1) and 0.026 ± 0.000 (s-1) in bone (N = 4) and liver (N = 2) metastases, respectively. Overall, high kPL showed concordance with biopsy-confirmed high-grade prostate cancer including neuroendocrine differentiation in one case. Interval decrease of kPL from 0.026 at baseline to 0.015 (s-1) was observed in a liver metastasis 2 months after the initiation of taxane plus platinum chemotherapy. RNA-seq found higher levels of the lactate dehydrogenase isoform A (Ldha,15.7 ± 0.7) expression relative to the dominant isoform of pyruvate dehydrogenase (Pdha1, 12.8 ± 0.9).ConclusionsHP 13C-pyruvate MRI can detect real-time glycolytic metabolism within prostate cancer metastases, and can measure changes in quantitative kPL values following treatment response at early time points. This first feasibility study supports future clinical studies of HP 13C-pyruvate MRI in the setting of advanced prostate cancer.

Hyperpolarized (HP) carbon 13 (13C) MRI is an emerging molecular imaging method that allows rapid, noninvasive, and pathway-specific investigation of dynamic metabolic and physiologic processes that were previously inaccessible to imaging. This technique has enabled real-time in vivo investigations of metabolism that are central to a variety of diseases, including cancer, cardiovascular disease, and metabolic diseases of the liver and kidney. This review provides an overview of the methods of hyperpolarization and 13C probes investigated to date in preclinical models of disease. The article then discusses the progress that has been made in translating this technology for clinical investigation. In particular, the potential roles and emerging clinical applications of HP [1-13C]pyruvate MRI will be highlighted. The future directions to enable the adoption of this technology to advance the basic understanding of metabolism, to improve disease diagnosis, and to accelerate treatment assessment are also detailed.

BackgroundThe liver R2* value is widely used as a measure of liver iron but may be confounded by the presence of hepatic steatosis and other covariates.PurposeTo identify the most influential covariates for liver R2* values in patients with nonalcoholic fatty liver disease (NAFLD).Study typeRetrospective analysis of prospectively acquired data.PopulationBaseline data from 204 subjects enrolled in NAFLD/NASH (nonalcoholic steatohepatitis) treatment trials.Field strength1.5T and 3T; chemical-shift encoded multiecho gradient echo.AssessmentCorrelation between liver proton density fat fraction and R2*; assessment for demographic, metabolic, laboratory, MRI-derived, and histological covariates of liver R2*.Statistical testsPearson's and Spearman's correlations; univariate analysis; gradient boosting machines (GBM) multivariable machine-learning method.ResultsHepatic proton density fat fraction (PDFF) was the most strongly correlated covariate for R2* at both 1.5T (r = 0.652, P

Effective coil combination methods for human hyperpolarized 13C spectroscopy multi-channel data had been relatively unexplored. This study implemented and tested several coil combination methods, including (1) the sum-of-squares (SOS), (2) singular value decomposition (SVD), (3) Roemer method by using reference peak area as a sensitivity map (RefPeak), and (4) Roemer method by using ESPIRiT-derived sensitivity map (ESPIRiT). These methods were evaluated by numerical simulation, thermal phantom experiments, and human cancer patient studies. Overall, the SVD, RefPeak, and ESPIRiT methods demonstrated better accuracy and robustness than the SOS method. Extracting complex pyruvate signal provides an easy and excellent approximation of the coil sensitivity map while maintaining valuable phase information of the coil-combined data.