Search

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).)

Purpose: To use the hepatocyte-specific gadolinium-based contrast agent gadoxetate combined with hyperpolarized (HP) [1- 13 C]pyruvate MRI to selectively suppress metabolic signals from normal hepatocytes while preserving the signals arising from tumors., Methods: Simulations were performed to determine the expected changes in HP 13 C MR signal in liver and tumor under the influence of gadoxetate. CC531 colon cancer cells were implanted into the livers of five Wag/Rij rats. Liver and tumor metabolism were imaged at 3 T using HP [1- 13 C] pyruvate chemical shift imaging before and 15 min after injection of gadoxetate. Area under the curve for pyruvate and lactate were measured from voxels containing at least 75% of normal-appearing liver or tumor., Results: Numerical simulations predicted a 36% decrease in lactate-to-pyruvate (L/P) ratio in liver and 16% decrease in tumor. In vivo, baseline L/P ratio was 0.44 ± 0.25 in tumors versus 0.21 ± 0.08 in liver (p = 0.09). Following administration of gadoxetate, mean L/P ratio decreased by an average of 0.11 ± 0.06 (p < 0.01) in normal-appearing liver. In tumors, mean L/P ratio post-gadoxetate did not show a statistically significant change from baseline. Compared to baseline levels, the relative decrease in L/P ratio was significantly greater in liver than in tumors (-0.52 ± 0.16 vs. -0.19 ± 0.25, p < 0.05)., Conclusions: The intracellular hepatobiliary contrast agent showed a greater effect suppressing HP 13 C MRI metabolic signals (through T 1 shortening) in normal-appearing liver when compared to tumors. The combined use of HP MRI with selective gadolinium contrast agents may allow more selective imaging in HP 13 C MRI., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background MR elastography (MRE) has been shown to have excellent performance for noninvasive liver fibrosis staging. However, there is limited knowledge regarding the precision and test-retest repeatability of stiffness measurement with MRE in the multicenter setting. Purpose To determine the precision and test-retest repeatability of stiffness measurement with MRE across multiple centers using the same phantoms. Materials and Methods In this study, three cylindrical phantoms made of polyvinyl chloride gel mimicking different degrees of liver stiffness in humans (phantoms 1-3: soft, medium, and hard stiffness, respectively) were evaluated. Between January 2021 and January 2022, phantoms were circulated between five different centers and scanned with 10 MRE-equipped clinical 1.5-T and 3-T systems from three major vendors, using two-dimensional (2D) gradient-recalled echo (GRE) imaging and/or 2D spin-echo (SE) echo-planar imaging (EPI). Similar MRE acquisition parameters, hardware, and reconstruction algorithms were used at each center. Mean stiffness was measured by a single observer for each phantom and acquisition on a single section. Stiffness measurement precision and same-session test-retest repeatability were assessed using the coefficient of variation (CV) and the repeatability coefficient (RC), respectively. Results The mean precision represented by the CV was 5.8% (95% CI: 3.8, 7.7) for all phantoms and both sequences combined. For all phantoms, 2D GRE achieved a CV of 4.5% (95% CI: 3.3, 5.7) whereas 2D SE EPI achieved a CV of 7.8% (95% CI: 3.1, 12.6). The mean RC of stiffness measurement was 5.8% (95% CI: 3.7, 7.8) for all phantoms and both sequences combined, 4.9% (95% CI: 2.7, 7.0) for 2D GRE, and 7.0% (95% CI: 2.9, 11.2) for 2D SE EPI (all phantoms). Conclusion MRE had excellent in vitro precision and same-session test-retest repeatability in the multicenter setting when similar imaging protocols, hardware, and reconstruction algorithms were used. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Tang in this issue.

Purpose: This study was motivated by the need for better positron emission tomography (PET)-compatible tools to image bacterial infection. Our previous efforts have targeted bacteria-specific metabolism via assimilation of carbon-11 labeled d-amino acids into the bacterial cell wall. Since the chemical determinants of this incorporation are not fully understood, we sought a high-throughput method to label d-amino acid derived structures with fluorine-18. Our strategy employed a chemical biology approach, whereby an azide (-N 3 ) bearing d-amino acid is incorporated into peptidoglycan muropeptides, with subsequent "click" cycloaddition with an 18 F-labeled strained cyclooctyne partner. Procedures: A water-soluble, 18 F-labeled and dibenzocyclooctyne (DBCO)-derived radiotracer ([ 18 F]FB-sulfo-DBCO) was synthesized. This tracer was incubated with pathogenic bacteria treated with azide-bearing d-amino acids, and incorporated 18 F was determined via gamma counting. In vitro uptake in bacteria previously treated with azide-modified d-amino acids was compared to that in cultures treated with amino acid controls. The biodistribution of [ 18 F]FB-sulfo-DBCO was studied in a cohort of healthy mice with implications for future in vivo imaging. Results: The new strain-promoted azide-alkyne cycloaddition (SPAAC) radiotracer [ 18 F]FB-sulfo-DBCO was synthesized with high radiochemical yield and purity via N -succinimidyl 4-[ 18 F]fluorobenzoate ([ 18 F]SFB). Accumulation of [ 18 F]FB-sulfo-DBCO was significantly higher in several bacteria treated with azide-modified d-amino acids than in controls; for example, we observed 7 times greater [ 18 F]FB-sulfo-DBCO ligation in Staphylococcus aureus cultures incubated with 3-azido-d-alanine versus those incubated with d-alanine. Conclusions: The SPAAC radiotracer [ 18 F]FB-sulfo-DBCO was validated in vitro via metabolic labeling of azide-bearing peptidoglycan muropeptides. d-Amino acid-derived PET radiotracers may be more efficiently screened via [ 18 F]FB-sulfo-DBCO modification.

Purpose: Nonalcoholic fatty liver disease is an important cause of chronic liver disease. There are limited methods for monitoring metabolic changes during progression to steatohepatitis. Hyperpolarized 13 C MRSI (HP 13 C MRSI) was used to measure metabolic changes in a rodent model of fatty liver disease., Methods: Fifteen Wistar rats were placed on a methionine- and choline-deficient (MCD) diet for 1-18 weeks. HP 13 C MRSI, T 2 -weighted imaging, and fat-fraction measurements were obtained at 3 T. Serum aspartate aminotransaminase, alanine aminotransaminase, and triglycerides were measured. Animals were sacrificed for histology and measurement of tissue lactate dehydrogenase (LDH) activity., Results: Animals lost significant weight (13.6% ± 2.34%), an expected characteristic of the MCD diet. Steatosis, inflammation, and mild fibrosis were observed. Liver fat fraction was 31.7% ± 4.5% after 4 weeks and 22.2% ± 4.3% after 9 weeks. Lactate-to-pyruvate and alanine-to-pyruvate ratios decreased significantly over the study course; were negatively correlated with aspartate aminotransaminase and alanine aminotransaminase (r = -[0.39-0.61]); and were positively correlated with triglycerides (r = 0.59-0.60). Despite observed decreases in hyperpolarized lactate signal, LDH activity increased by a factor of 3 in MCD diet-fed animals. Observed decreases in lactate and alanine hyperpolarized signals on the MCD diet stand in contrast to other studies of liver injury, where lactate and alanine increased. Observed hyperpolarized metabolite changes were not explained by alterations in LDH activity, suggesting that changes may reflect co-factor depletion known to occur as a result of oxidative stress in the MCD diet., Conclusion: HP 13 C MRSI can noninvasively measure metabolic changes in the MCD model of chronic liver disease., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Imaging infections in patients is challenging using conventional methods, motivating the development of positron emission tomography (PET) radiotracers targeting bacteria-specific metabolic pathways. Numerous techniques have focused on the bacterial cell wall, although peptidoglycan-targeted PET tracers have been generally limited to the short-lived carbon-11 radioisotope ( t 1/2 = 20.4 min). In this article, we developed and tested new tools for infection imaging using an amino sugar component of peptidoglycan, namely, derivatives of N -acetyl muramic acid (NAM) labeled with the longer-lived fluorine-18 ( t 1/2 = 109.6 min) radioisotope. Muramic acid was reacted directly with 4-nitrophenyl 2-[ 18 F]fluoropropionate ([ 18 F]NFP) to afford the enantiomeric NAM derivatives ( S )-[ 18 F]FMA and ( R )-[ 18 F]FMA. Both diastereomers were easily isolated and showed robust accumulation by human pathogens in vitro and in vivo, including Staphylococcus aureus . These results form the basis for future clinical studies using fluorine-18-labeled NAM-derived PET radiotracers.

Background The Liver Imaging Reporting and Data System version 2018 (LI-RADS) treatment response algorithm (TRA) is a high-specificity, lower-sensitivity grading system to diagnose hepatocellular carcinoma (HCC) and recurrence after local-regional therapy. However, the emphasis on specificity can result in disease understaging, potentially leading to poorer posttransplant outcomes. Purpose To determine the negative predictive value (NPV) of pretransplant CT and MRI assessment for viable HCC on a per-patient basis using the LI-RADS TRA, considering explant pathology as the reference standard. Materials and Methods Patient records from 218 consecutive adult patients from a single institution with HCC who underwent liver transplant from January 2011 to November 2017 were retrospectively reviewed. Two readers blinded to the original report reviewed immediate (within 90 days) pretransplant imaging and characterized observations according to the LI-RADS TRA. Based on this, patients with LR-4, LR-5, or LR-TR (treatment response) viable tumors were designated as viable tumor; patients with solely LR-3 or LR-TR equivocal tumors were designated as equivocal; and patients with only LR-TR nonviable lesions were designated as no viable disease. Patients were designated as within or outside the Milan criteria. These per-patient designations were compared with the presence of viable disease at explant pathology. Fisher exact test was used to compare the differences between CT and MRI. Weighted κ values were used to calculate interreader reliability. Results Final study sample consisted of 206 patients (median age, 61 years [IQR, 57-65 years]; 157 male patients and 49 female patients). Per-patient LI-RADS TRA assessment of pretransplant imaging had an NPV of 32% (95% CI: 27, 38) and 26% (95% CI: 20, 33) (readers 1 and 2, respectively) for predicting viable disease. Seventy-five percent (reader 1) and 77% (reader 2) of patients deemed equivocal had residual tumors at explant pathology. Weighted interreader reliability was substantial (κ = 0.62). Conclusion Patient-based stratification of viable, equivocal, and nonviable disease at pretransplant CT or MRI, based on LI-RADS TRA, demonstrated low negative predictive value in excluding HCC at explant pathology. © RSNA, 2023 See also the editorial by Tamir and Tau in this issue.

Background: Vertebral discitis-osteomyelitis (VDO) is a devastating infection of the spine that is challenging to distinguish from noninfectious mimics using computed tomography and magnetic resonance imaging. We and others have developed novel metabolism-targeted positron emission tomography (PET) radiotracers for detecting living Staphylococcus aureus and other bacteria in vivo, but their head-to-head performance in a well-validated VDO animal model has not been reported., Methods: We compared the performance of several PET radiotracers in a rat model of VDO. [11C]PABA and [18F]FDS were assessed for their ability to distinguish S aureus, the most common non-tuberculous pathogen VDO, from Escherichia coli., Results: In the rat S aureus VDO model, [11C]PABA could detect as few as 103 bacteria and exhibited the highest signal-to-background ratio, with a 20-fold increased signal in VDO compared to uninfected tissues. In a proof-of-concept experiment, detection of bacterial infection and discrimination between S aureus and E coli was possible using a combination of [11C]PABA and [18F]FDS., Conclusions: Our work reveals that several bacteria-targeted PET radiotracers had sufficient signal to background in a rat model of S aureus VDO to be potentially clinically useful. [11C]PABA was the most promising tracer investigated and warrants further investigation in human VDO., Competing Interests: Potential conflicts of interest. The authors: No potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chemoenzymatic techniques have been applied extensively to pharmaceutical development, most effectively when routine synthetic methods fail. The regioselective and stereoselective construction of structurally complex glycans is an elegant application of this approach that is seldom applied to positron emission tomography (PET) tracers. We sought a method to dimerize 2-deoxy-[ 18 F]-fluoro-d-glucose ([ 18 F]FDG), the most common tracer used in clinical imaging, to form [ 18 F]-labeled disaccharides for detecting microorganisms in vivo based on their bacteria-specific glycan incorporation. When [ 18 F]FDG was reacted with β-d-glucose-1-phosphate in the presence of maltose phosphorylase, the α-1,4- and α-1,3-linked products 2-deoxy-[ 18 F]-fluoro-maltose ([ 18 F]FDM) and 2-deoxy-2-[ 18 F]-fluoro-sakebiose ([ 18 F]FSK) were obtained. This method was further extended with the use of trehalose (α,α-1,1), laminaribiose (β-1,3), and cellobiose (β-1,4) phosphorylases to synthesize 2-deoxy-2-[ 18 F]fluoro-trehalose ([ 18 F]FDT), 2-deoxy-2-[ 18 F]fluoro-laminaribiose ([ 18 F]FDL), and 2-deoxy-2-[ 18 F]fluoro-cellobiose ([ 18 F]FDC). We subsequently tested [ 18 F]FDM and [ 18 F]FSK in vitro , showing accumulation by several clinically relevant pathogens including Staphylococcus aureus and Acinetobacter baumannii , and demonstrated their specific uptake in vivo. Both [ 18 F]FDM and [ 18 F]FSK were stable in human serum with high accumulation in preclinical infection models. The synthetic ease and high sensitivity of [ 18 F]FDM and [ 18 F]FSK to S. aureus including methicillin-resistant (MRSA) strains strongly justify clinical translation of these tracers to infected patients. Furthermore, this work suggests that chemoenzymatic radiosyntheses of complex [ 18 F]FDG-derived oligomers will afford a wide array of PET radiotracers for infectious and oncologic applications.

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.

Quantitative imaging biomarkers of liver disease measured by using MRI and US are emerging as important clinical tools in the management of patients with chronic liver disease (CLD). Because of their high accuracy and noninvasive nature, in many cases, these techniques have replaced liver biopsy for the diagnosis, quantitative staging, and treatment monitoring of patients with CLD. The most commonly evaluated imaging biomarkers are surrogates for liver fibrosis, fat, and iron. MR elastography is now routinely performed to evaluate for liver fibrosis and typically combined with MRI-based liver fat and iron quantification to exclude or grade hepatic steatosis and iron overload, respectively. US elastography is also widely performed to evaluate for liver fibrosis and has the advantage of lower equipment cost and greater availability compared with those of MRI. Emerging US fat quantification methods can be performed along with US elastography. The author group, consisting of members of the Society of Abdominal Radiology (SAR) Liver Fibrosis Disease-Focused Panel (DFP), the SAR Hepatic Iron Overload DFP, and the European Society of Radiology, review the basics of liver fibrosis, fat, and iron quantification with MRI and liver fibrosis and fat quantification with US. The authors cover technical requirements, typical case display, quality control and proper measurement technique and case interpretation guidelines, pitfalls, and confounding factors. The authors aim to provide a practical guide for radiologists interpreting these examinations. © RSNA, 2023 See the invited commentary by Ronot in this issue. Quiz questions for this article are available in the supplemental material.

Background & Aims: Non-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., Methods: Adult 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., Results: Treatment 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)., Conclusions: In 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 Number: NCT01265498., Impact and Implications: Although 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., (Copyright © 2022 European Association for the Study of the Liver. All rights reserved.)

Purpose: To develop techniques and establish a workflow using hyperpolarized carbon-13 ( 13 C) MRI and the pyruvate-to-lactate conversion rate (k PL ) biomarker to guide MR-transrectal ultrasound fusion prostate biopsies., Methods: The 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 k PL values were calculated, uploaded to a picture archiving and communication system and targeting platform, and displayed as color overlays on T 2 -weighted anatomic images. Abdominal radiologists identified 13 C research biopsy targets based on the general recommendation of focal lesions with k PL  >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-k PL targets. All biopsy results were included in the final pathology report and calculated toward clinical risk., Results: This 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-k PL 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 k PL of 0.0319 s -1 (range: 0.0198-0.0410)., Conclusions: This 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., (© 2022 International Society for Magnetic Resonance in Medicine.)

Background: Hyperpolarized 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., Purpose: Image 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 Type: Prospective technical development., Subjects: A total of 13 healthy volunteers (8 male), 21-64 years (median 36)., Field Strength/sequence: A 3 T. Proton: T 1 -weighted spoiled gradient echo, T 2 -weighted single-shot fast spin echo, multiecho fat/water imaging. Carbon-13: echo-planar spectroscopic imaging, metabolite-specific echo-planar imaging., Assessment: Transmit magnetic field was measured. Variations in main magnetic field (ΔB 0 ) determined using multiecho proton acquisitions were compared to carbon-13 acquisitions. Changes in ΔB 0 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 (k PL ) and alanine (k PA ) conversion were measured in each organ., Statistical Tests: Linear regression, one-sample Kolmogorov-Smirnov tests, paired t-tests, one-way ANOVA, Tukey's multiple comparisons tests. P ≤ 0.05 considered statistically significant., Results: Proton ΔB 0 maps correlated with carbon-13 ΔB 0 maps (slope = 0.93, y-intercept = -2.88, R 2  = 0.73). Localized shimming resulted in mean frequency offset within ±25 Hz for all organs. Metabolite SNR significantly increased after denoising. Mean k PL and k PA were highest in liver, followed by pancreas, spleen, and kidneys (all comparisons with liver were significant)., Data Conclusion: Whole-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 Level: 2 TECHNICAL EFFICACY: Stage 1., (© 2022 International Society for Magnetic Resonance in Medicine.)

Purpose: Non-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- 11 C-methionine (D- 11 C-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- 11 C-Met in patients with suspected prosthetic joint infections., Methods: 614.5 ± 100.2 MBq of D- 11 C-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. SUV max and SUV peak 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., Results: D- 11 C-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- 11 C-Met showed increased focal uptake in areas of suspected infection, demonstrated by a significantly higher SUV max and SUV peak calculated from VOIs of joints with suspected infections compared to the contralateral joints, blood pool, and background (P < 0.01). Furthermore, higher distribution volume and binding potential were observed in suspected infections compared to the unaffected joints., Conclusion: D- 11 C-Met has a favorable radiation profile, minimal background uptake, and fast urinary extraction. Furthermore, D- 11 C-Met showed increased uptake in areas of suspected infection, making this a promising approach. Validation in larger clinical trials with a rigorous gold standard is still required., (© 2022. The Author(s).)

The liver's unique blood supply facilitates multiple important physiologic roles. Liver vascular disorders have distinct appearances on imaging examinations and may mimic other pathologies. This article reviews the imaging appearances of vascular disorders from a multimodality perspective. Liver vascular pathologies are categorized by how they affect liver inflow, liver outflow, and those with abnormal arterial-venous connections. By understanding the physiologic and pathologic underpinnings of the hepatic vasculature, the radiologist is well positioned to positively affect patient care., Competing Interests: Disclosure Both authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Determine whether liver attenuation measured on dual-energy CT (DECT) virtual non-contrast examinations predicts the presence of fatty liver., Methods: Single-institution retrospective review from 2016 to 2020 found patients with DECT and proton density fat fraction MRI (MRI PDFF) within 30 days. MRI PDFF was the reference standard for determining hepatic steatosis. Attenuation measurements from VNC and mixed 120 kVp-like images were compared to MRI PDFF in the right and left lobes. Performance of VNC was compared to measurement of the liver-spleen attenuation difference (LSAD)., Results: 128 patients were included (69 men, 59 women) with mean age 51.6 years (range 14-98 years). > 90% of patients received CT and MRI in the emergency department or as inpatients. Median interval between DECT and MRI PDFF was 2 days (range 0-28 days). Prevalence of fatty liver using the reference standard (MRI PDFF > 6%) was 24%. Pearson correlation coefficient between VNC and MRI- DFF was -0.64 (right) and -0.68 (left, both p < 0.0001). For LSAD, correlation was - 0.43 in both lobes (p < 0.0001). Considering MRI PDFF > 6% as diagnostic of steatosis, area under the receiver operator characteristic curve (AUC) was 0.834 and 0.872 in the right and left hepatic lobes, with an optimal threshold of 54.8 HU (right) and 52.5 HU (left), yielding sensitivity/specificity of 57%/93.9% (right) and 67.9%/90% (left). For LSAD, AUC was 0.808 (right) and 0.767 (left) with optimal sensitivity/specificity of 93.3%/57.1% (right) and 78.6%/68% (left)., Conclusion: Attenuation measured at VNC CT was moderately correlated with liver fat content and had > 90% specificity for diagnosis of fatty liver., (© 2022. The Author(s).)

In this case report, dual-energy CT was critical in the diagnosis of acute mesenteric ischemia by differentiating normal contrast-enhanced bowel and hemorrhagic necrosis. Iodine map showed a segment of small bowel with minimal contrast enhancement, and virtual non-contrast imaging revealed hyperattenuating bowel. This finding changed management for the patient and prevented complications from impending bowel perforation. Histopathological analysis confirmed hemorrhagic necrosis of the bowel segment. In cases of suspected bowel ischemia, dual-energy CT can distinguish bowel wall hemorrhage from contrast enhancement and allow for accurate diagnosis., (© 2022. American Society of Emergency Radiology.)

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.)

BACKGROUND . The value of dual-energy CT (DECT) for bowel wall assessment is increasingly recognized. Although technical improvements reduce peristalsis artifact in conventional CT, the effects of peristalsis on DECT image reconstructions remain poorly studied. OBJECTIVE . The purpose of this study was to evaluate the influence of different DECT scanners and enteric contrast agents on the severity of bowel peristalsis artifact in vitro. METHODS . To simulate bowel peristalsis, a 3-cm-diameter corrugated hollow tube representing the bowel was oscillated constantly in the z -axis within a larger water-filled cylinder. The bowel was serially filled with air, water, and iodinated or experimental dark contrast material and scanned on four different DECT platforms (spectral detector, rapid peak kilovoltage switching, split filter, and dual source) to reconstruct 120-kVp-like and iodine images. Two readers rated each image reconstruction for artifact severity from 0 (none) to 3 (severe) and recorded the degree to which iodine images depicted bowel wall hyperattenuation on 120-kVp-like images as artifactual. Artifact severity scores were compared by ANOVA with Bonferroni correction. RESULTS . Interrater agreement on artifact scores was excellent (intraclass correlation coefficient, 0.82 [95% CI, 0.79-0.84]). For 120-kVp-like images, mean peristalsis artifact scores were lower (all p < .001) for split-filter (1.47) and dual-source (1.86) scanners than for spectral-detector (2.58) and rapid-kilovoltage-switching (2.74) scanners. Compared with those on 120-kVp images, peristalsis artifacts on iodine images were less severe for spectral-detector (score, 1.03; p < .001) and rapid-kilovoltage-switching (2.09; p < .001) systems but more severe for dual-source (2.77; p < .001) and split-filter (2.62; p < .001) systems. Peristalsis artifact was rated less severe with experimental dark bowel contrast medium (score, 1.79) than with other bowel contrast agents (all p < .001). Iodine images helped identify bowel wall hyperattenuation as artifactual in 94.7% of reviewed cases for spectral-detector and 40.7% of cases for rapid-kilovoltage-switching scanners. CONCLUSION . For spectral-detector and rapid-kilovoltage-switching DECT, iodine images minimize peristalsis artifact, but for dual-source and split-filter DECT, mixed 120-kVp-like images are preferred. Compared with iodinated contrast material and water, experimental dark bowel contrast material reduces peristalsis artifact. CLINICAL IMPACT . Knowledge of the preferred images for reducing peristalsis artifact can lessen the effect of peristalsis on clinical DECT interpretation. Dark enteric contrast agents, when they become clinically available, may further reduce the effects of peristalsis.

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.)

The growing demand for metabolism-specific imaging techniques has rekindled interest in Deuterium ( 2 H) Metabolic Imaging (DMI), a robust method based on administration of a substrate (glucose, acetate, fumarate, etc.) labeled with the stable isotope of hydrogen and the observation of its metabolic fate in three-dimensions. This technique allows the investigation of multiple metabolic processes in both healthy and diseased states. Despite its low natural abundance, the short relaxation time of deuterium allows for rapid radiofrequency (RF) pulses without saturation and efficient image acquisition. In this review, we provide a comprehensive picture of the evolution of DMI over the course of recent decades, with a special focus on its potential clinical applications.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease that manifests as vascular malformations in the brain, lung, liver, gastrointestinal tract, nasal mucosa, and skin. Diagnosis and management of HHT is guided in large part by imaging studies, making it a condition with which the radiology community needs familiarity. Proper screening and care lead to improved morbidity and mortality in patients with HHT. International guidelines were recently updated and form the basis for a detailed discussion of the role of imaging and image-guided therapy in HHT. © RSNA, 2021 Online supplemental material is available for this article.

Existing clinical markers for renal disease are limited. Hyperpolarized (HP) 13 C 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 [ 13 C]urea, a metabolically inert tracer. Metabolic changes can be assessed using [1- 13 C]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 13 C 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.

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.)

Increased mortality rates from infectious diseases is a growing public health concern. Successful management of acute bacterial infections requires early diagnosis and treatment, which are not always easy to achieve. Structural imaging techniques such as CT and MRI are often applied to this problem. However, these methods generally rely on secondary inflammatory changes and are frequently not specific to infection. The use of nuclear medicine techniques can add crucial complementary information, allowing visualization of infectious pathophysiology beyond morphologic imaging. This review will discuss the current structural and functional imaging techniques used for the diagnosis of bacterial infection and their roles in different clinical scenarios. We will also present several new radiotracers in development, with an emphasis on probes targeting bacteria-specific metabolism. As highlighted by the current coronavirus disease 2019 epidemic, caused by the novel severe acute respiratory syndrome coronavirus 2, similar thinking may apply in imaging viral pathogens; for this case, prominent effects on host proteins, most notably angiotensin-converting enzyme 2, might also provide worthwhile imaging targets., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To subjectively and quantitatively compare the quality of 3 Tesla magnetic resonance imaging of the prostate acquired with a novel flexible surface coil (FSC) and with a conventional endorectal coil (ERC)., Methods: Six radiologists independently reviewed 200 pairs of axial, high-resolution T2-weighted and diffusion-weighted image data sets, each containing one examination acquired with the FSC and one with the ERC, respectively. Readers selected their preferred examination from each pair and assessed every single examination using six quality criteria on 4-point scales. Signal-to-noise ratios were measured and compared., Results: Two readers preferred FSC acquisition (36.5-45%) over ERC acquisition (13.5-15%) for both sequences combined, and four readers preferred ERC acquisition (41-46%). Analysis of pooled responses for both sequences from all readers shows no significant preference for FSC or ERC. Analysis of the individual sequences revealed a pooled preference for the FSC in T2WI (38.7% vs 17.8%) and for the ERC in DWI (50.9% vs 19.6%). Patients' weight was the only weak predictor of a preference for the ERC acquisition (p = 0.04). SNR and CNR were significantly higher in the ERC acquisitions (p<0.001) except CNR differentiating tumor lesions from benign prostate (p=0.1)., Conclusion: Although readers have strong individual preferences, comparable subjective image quality can be obtained for prostate MRI with an ERC and the novel FSC. ERC imaging might be particularly valuable for sequences with inherently lower SNR as DWI and larger patients whereas the FSC is generally preferred in T2WI. FSC imaging generates a lower SNR than with an ERC.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by spontaneous epistaxis, telangiectasia, and visceral vascular malformations. Hepatic vascular malformations are common, though a minority are symptomatic. Symptoms are dependent on the severity and exact type of shunting caused by the hepatic malformation: Arteriosystemic shunting leads to manifestations of high output cardiac failure, and arterioportal shunting leads to portal hypertension. Radiologic imaging, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), is an important tool for assessing liver involvement. Doppler ultrasonography is the first-line screening modality for HHT-related liver disease, and it has a standardized scale. Imaging can determine whether shunting is principally to the hepatic vein or the portal vein, which can be a key determinant of patients' symptoms. Liver-related complications can be detected, including manifestations of portal hypertension, focal liver masses as well as ischemic cholangiopathy. Ultrasound and MRI also have the ability to quantify blood flow through the liver, which in the future may be used to determine prognosis and direct antiangiogenic therapy.

The aim of this study was to use texture analysis to establish quantitative CT-based imaging features to predict clinical severity in patients with acute alcohol-associated hepatitis (AAH). A secondary aim was to compare the performance of texture analysis to deep learning. In this study, mathematical texture features were extracted from CT slices of the liver for 34 patients with a diagnosis of AAH and 35 control patients. Recursive feature elimination using random forest (RFE-RF) was used to identify the best combination of features to distinguish AAH from controls. These features were subsequently used as predictors to determine associated clinical values. To compare machine learning with deep learning approaches, a 2D dense convolutional neural network (CNN) was implemented and trained for the classification task of AAH. RFE-RF identified 23 top features used to classify AAH images, and the subsequent model demonstrated an accuracy of 82.4% in the test set. The deep learning CNN demonstrated an accuracy of 70% in the test set. We show that texture features of the liver are unique in AAH and are candidate quantitative biomarkers that can be used in prospective studies to predict the severity and outcomes of patients with AAH.

This review highlights recent efforts to detect bacteria using engineered small molecules that are processed and incorporated similarly to their natural counterparts. There are both scientific and clinical justifications for these endeavors. The use of detectable, cell-wall targeted chemical probes has elucidated microbial behavior, with several fluorescent labeling methods in widespread laboratory use. Furthermore, many existing efforts including ours, focus on developing new imaging tools to study infection in clinical practice. The bacterial cell wall, a remarkably rich and complex structure, is an outstanding target for bacteria-specific detection. Several cell wall components are found in bacteria but not mammals, especially peptidoglycan, lipopolysaccharide, and teichoic acids. As this review highlights, the development of laboratory tools for fluorescence microscopy has vastly outstripped related positron emission tomography (PET) or single photon emission computed tomography (SPECT) radiotracer development. However, there is great synergy between these chemical strategies, which both employ mimicry of endogenous substrates to incorporate detectable structures. As the field of bacteria-specific imaging grows, it will be important to understand the mechanisms involved in microbial incorporation of radionuclides. Additionally, we will highlight the clinical challenges motivating this imaging effort.

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.

Purpose: Detection of bacteria-specific metabolism via positron emission tomography (PET) is an emerging strategy to image human pathogens, with dramatic implications for clinical practice. In silico and in vitro screening tools have recently been applied to this problem, with several monosaccharides including l-arabinose showing rapid accumulation in Escherichia coli and other organisms. Our goal for this study was to evaluate several synthetically viable arabinofuranose-derived 18 F analogs for their incorporation into pathogenic bacteria., Procedures: We synthesized four radiolabeled arabinofuranose-derived sugars: 2-deoxy-2-[ 18 F]fluoro-arabinofuranoses (d-2- 18 F-AF and l-2- 18 F-AF) and 5-deoxy-5-[ 18 F]fluoro-arabinofuranoses (d-5- 18 F-AF and l-5- 18 F-AF). The arabinofuranoses were synthesized from 18 F - via triflated, peracetylated precursors analogous to the most common radiosynthesis of 2-deoxy-2-[ 18 F]fluoro-d-glucose ([ 18 F]FDG). These radiotracers were screened for their uptake into E. coli and Staphylococcus aureus. Subsequently, the sensitivity of d-2- 18 F-AF and l-2- 18 F-AF to key human pathogens was investigated in vitro., Results: All 18 F radiotracer targets were synthesized in high radiochemical purity. In the screening study, d-2- 18 F-AF and l-2- 18 F-AF showed greater accumulation in E. coli than in S. aureus. When evaluated in a panel of pathologic microorganisms, both d-2- 18 F-AF and l-2- 18 F-AF demonstrated sensitivity to most gram-positive and gram-negative bacteria., Conclusions: Arabinofuranose-derived 18 F PET radiotracers can be synthesized with high radiochemical purity. Our study showed absence of bacterial accumulation for 5-substitued analogs, a finding that may have mechanistic implications for related tracers. Both d-2- 18 F-AF and l-2- 18 F-AF showed sensitivity to most gram-negative and gram-positive organisms. Future in vivo studies will evaluate the diagnostic accuracy of these radiotracers in animal models of infection., (© 2020 John Wiley & Sons, Ltd.)

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.)

Incorporation of d-amino acids into peptidoglycan is a unique metabolic feature of bacteria. Since d-amino acids are not metabolic substrates in most mammalian tissues, this difference can be exploited to detect living bacteria in vivo . Given the prevalence of d-alanine in peptidoglycan muropeptides, as well as its role in several antibiotic mechanisms, we targeted this amino acid for positron emission tomography (PET) radiotracer development. d-[3- 11 C]Alanine and the dipeptide d-[3- 11 C]alanyl-d-alanine were synthesized via asymmetric alkylation of glycine-derived Schiff-base precursors with [ 11 C]methyl iodide in the presence of a cinchonidinium phase-transfer catalyst. In cell experiments, both tracers showed accumulation by a wide variety of both Gram-positive and Gram-negative pathogens including Staphylococcus aureus and Pseudomonas aeruginosa . In a mouse model of acute bacterial myositis, d-[3- 11 C]alanine was accumulated by living microorganisms but was not taken up in areas of sterile inflammation. When compared to existing clinical nuclear imaging tools, specifically 2-deoxy-2-[ 18 F]fluoro-d-glucose and a gallium citrate radiotracer, d-alanine showed more bacteria-specific uptake. Decreased d-[3- 11 C]alanine uptake was also observed in antibiotic-sensitive microbes after antimicrobial therapy, when compared to that in resistant organisms. Finally, prominent uptake of d-[3- 11 C]alanine uptake was seen in rodent models of discitis-osteomyelitis and P. aeruginosa pneumonia. These data provide strong justification for clinical translation of d-[3- 11 C]alanine to address a number of important human infections., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

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.)

Effective coil combination methods for human hyperpolarized 13 C 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)