Dynamic T 2 * relaxometry of hyperpolarized [1-13 C]pyruvate MRI in the human brain and kidneys.

PURPOSE: This study aimed to quantify T 2 * $$ {T}_2^{\ast } $$ for hyperpolarized [1-13 C]pyruvate and metabolites in the healthy human brain and renal cell carcinoma (RCC) patients at 3 T. METHODS: Dynamic T 2 * $$ {T}_2^{\ast } $$ values were measured with a metabolite-specific multi-echo spiral sequence. The dynamic T 2 * $$ {T}_2^{\ast } $$ of [1-13 C]pyruvate, [1-13 C]lactate, and 13 C-bicarbonate was estimated in regions of interest in the whole brain, sinus vein, gray matter, and white matter in healthy volunteers, as well as in kidney tumors and the contralateral healthy kidneys in a separate group of RCC patients. T 2 * $$ {T}_2^{\ast } $$ was fit using a mono-exponential function; and metabolism was quantified using pyruvate-to-lactate conversion rate maps and lactate-to-pyruvate ratio maps, which were compared with and without an estimated T 2 * $$ {T}_2^{\ast } $$ correction. RESULTS: The T 2 * $$ {T}_2^{\ast } $$ of pyruvate was shown to vary during the acquisition, whereas the T 2 * $$ {T}_2^{\ast } $$ of lactate and bicarbonate were relatively constant through time and across the organs studied. The T 2 * $$ {T}_2^{\ast } $$ of lactate was similar in gray matter (29.75 ± 1.04 ms), white matter (32.89 ± 0.9 ms), healthy kidney (34.61 ± 4.07 ms), and kidney tumor (33.01 ± 2.31 ms); and the T 2 * $$ {T}_2^{\ast } $$ of bicarbonate was different between whole-brain (108.17 ± 14.05 ms) and healthy kidney (58.45 ± 6.63 ms). The T 2 * $$ {T}_2^{\ast } $$ of pyruvate had similar trends in both brain and RCC studies, reducing from 75.56 ± 2.23 ms to 22.24 ± 1.24 ms in the brain and reducing from 122.72 ± 9.86 ms to 57.38 ± 7.65 ms in the kidneys. CONCLUSION: Multi-echo dynamic imaging can quantify T 2 * $$ {T}_2^{\ast } $$ and metabolism in a single integrated acquisition. Clear differences were observed in the T 2 * $$ {T}_2^{\ast } $$ of metabolites and in their behavior throughout the timecourse.

Hyperpolarized 13 C metabolic imaging of the human abdomen with spatiotemporal denoising.

PURPOSE: Improving the quality and maintaining the fidelity of large coverage abdominal hyperpolarized (HP) 13 C MRI studies with a patch based global-local higher-order singular value decomposition (GL-HOVSD) spatiotemporal denoising approach. METHODS: Denoising performance was first evaluated using the simulated [1-13 C]pyruvate dynamics at different noise levels to determine optimal kglobal and klocal parameters. The GL-HOSVD spatiotemporal denoising method with the optimized parameters was then applied to two HP [1-13 C]pyruvate EPI abdominal human cohorts (n = 7 healthy volunteers and n = 8 pancreatic cancer patients). RESULTS: The parameterization of kglobal = 0.2 and klocal = 0.9 denoises abdominal HP data while retaining image fidelity when evaluated by RMSE. The kPX (conversion rate of pyruvate-to-metabolite, X = lactate or alanine) difference was shown to be <20% with respect to ground-truth metabolic conversion rates when there is adequate SNR (SNRAUC > 5) for downstream metabolites. In both human cohorts, there was a greater than nine-fold gain in peak [1-13 C]pyruvate, [1-13 C]lactate, and [1-13 C]alanine apparent SNRAUC . The improvement in metabolite SNR enabled a more robust quantification of kPL and kPA . After denoising, we observed a 2.1 ± 0.4 and 4.8 ± 2.5-fold increase in the number of voxels reliably fit across abdominal FOVs for kPL and kPA quantification maps. CONCLUSION: Spatiotemporal denoising greatly improves visualization of low SNR metabolites particularly [1-13 C]alanine and quantification of [1-13 C]pyruvate metabolism in large FOV HP 13 C MRI studies of the human abdomen.

Initial Experience of Metabolic Imaging With Hyperpolarized [1-13C]pyruvate MRI in Kidney Transplant Patients.

BACKGROUND: Kidney transplant is the treatment of choice for patients with end-stage renal disease. Early detection of allograft injury is important to delay or prevent irreversible damage. PURPOSE: To investigate the feasibility of hyperpolarized (HP) [1-13C]pyruvate MRI for assessing kidney allograft metabolism. STUDY TYPE: Prospective. SUBJECTS: Six participants (mean age, 45.2 ± 12.4 years, two females) scheduled for kidney allograft biopsy and five patients (mean age, 59.6 ± 10.4 years, two females) with renal cell carcinoma (RCC). FIELD STRENGTH/SEQUENCE: Three Tesla, T2-weighted fast spin echo, multi-echo gradient echo, single shot diffusion-weighted echo-planar imaging, and time-resolved HP 13C metabolite-selective imaging. ASSESSMENT: Five of the six kidney allograft participants underwent biopsy after MRI. Estimated glomerular filtration rate (eGFR) and urine protein-to-creatine ratio (uPCR) were collected within 4 weeks of MRI. Kidney metabolism was quantified from HP [1-13C]pyruvate MRI using the lactate-to-pyruvate ratio in allograft kidneys and non-tumor bearing kidneys from RCC patients. STATISTICAL TESTS: Descriptive statistics (mean ± SD). RESULTS: Biopsy was performed a mean of 9 days (range 5-19 days) after HP [1-13C]pyruvate MRI. Three biopsies were normal, one showed low-grade fibrosis and one showed moderate microvascular inflammation. All had stable functioning allografts with eGFR >60 mL/min/1.73 m2 and normal uPCR. One participant who did not undergo biopsy had reduced eGFR of 49 mL/min/1.73 m2 and elevated uPCR. The mean lactate-to-pyruvate ratio was 0.373 in participants with normal findings (N = 3) and 0.552 in participants with abnormal findings (N = 2). The lactate-to-pyruvate ratio was highest (0.847) in the participant with reduced eGFR and elevated uPRC. Native non-tumor bearing kidneys had a mean lactate-to-pyruvate ratio of 0.309. DATA CONCLUSION: Stable allografts with normal findings at biopsy showed lactate-to-pyruvate ratios similar to native non-tumor bearing kidneys, whereas allografts with abnormal findings showed higher lactate-to-pyruvate ratios. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Pancreatic Cyst Surveillance: Who, Why, How?

Pancreatic cystic lesions (PCLs) are widely prevalent and commonly encountered in abdominal radiology. Some PCLs can be definitively identified at imaging as benign subtypes or those with malignant potential, while others remain indeterminate. Notably, the degree of malignant potential and natural history of the most common subtype, branch-duct intraductal papillary mucinous neoplasms, are not clearly established. In the work-up of PCLs, patients may further be identified as high-risk individuals who are at elevated risk of pancreatic ductal adenocarcinoma due to familial and genetic factors. This review describes current PCL surveillance and management guidelines and highlights ongoing controversies and future directions to aid radiologists in their daily practice.

Hyperpolarized 13 C Metabolic MRI of Patients with Pancreatic Ductal Adenocarcinoma.

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.

Improving multiparametric MR-transrectal ultrasound guided fusion prostate biopsies with hyperpolarized 13 C pyruvate metabolic imaging: A technical development study.

PURPOSE: To 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. 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 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. 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-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). 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.

Whole-Abdomen Metabolic Imaging of Healthy Volunteers Using Hyperpolarized [1-13 C]pyruvate MRI.

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: 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. ASSESSMENT: Transmit 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 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 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 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.

Bowel Peristalsis Artifact on Dual-Energy CT: In Vitro Study on the Influence of Different Dual-Energy CT Platforms and Enteric Contrast Agents.

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.

Positive Versus Neutral Oral Contrast Material for Detection of Malignant Deposits in Intraabdominal Nonsolid Organs on CT.

BACKGROUND. Data are limited regarding utility of positive oral contrast material for peritoneal tumor detection on CT. OBJECTIVE. The purpose of this article is to compare positive versus neutral oral contrast material for detection of malignant deposits in nonsolid intraabdominal organs on CT. METHODS. This retrospective study included 265 patients (133 men, 132 women; median age, 61 years) who underwent an abdominopelvic CT examination in which the report did not suggest presence of malignant deposits and a subsequent CT examination within 6 months in which the report indicated at least one unequivocal malignant deposit. Examinations used positive (iohexol; n = 100) or neutral (water; n = 165) oral agents. A radiologist reviewed images to assess whether the deposits were visible (despite clinical reports indicating no deposits) on unblinded comparison with the follow-up examinations; identified deposits were assigned to one of seven intraabdominal compartments. The radiologist also assessed adequacy of bowel filling with oral contrast material. Two additional radiologists independently reviewed examinations in blinded fashion for malignant deposits. NPV was assessed of clinical CT reports and blinded retrospective readings for detection of malignant deposits visible on unblinded comparison with follow-up examinations. RESULTS. Unblinded review identified malignant deposits in 58.1% (154/265) of examinations. In per-patient analysis of clinical reports, NPV for malignant deposits was higher for examinations with adequate bowel filling with positive oral contrast material (65.8% [25/38]) than for examinations with inadequate bowel filling with positive oral contrast material (45.2% [28/62], p = .07) or with neutral oral contrast material regardless of bowel filling adequacy (35.2% [58/165], p = .002). In per-compartment analysis of blinded interpretations, NPV was higher for examinations with adequate and inadequate bowel filling with positive oral contrast material than for examinations with neutral oral contrast regardless of bowel filling adequacy (reader 1: 94.7% [234/247] and 92.5% [382/413] vs 88.3% [947/1072], both p = .045; reader 2: 93.1% [228/245] and 91.6% [361/394] vs 85.9% [939/1093], both p = .01). CONCLUSION. CT has suboptimal NPV for malignant deposits in intraabdominal nonsolid organs. Compared with neutral material, positive oral contrast material improves detection, particularly with adequate bowel filling. CLINICAL IMPACT. Optimization of bowel preparation for oncologic CT may help avoid potentially severe clinical consequences of missed malignant deposits.

Specialized computational methods for denoising, B1 correction, and kinetic modeling in hyperpolarized 13 C MR EPSI studies of liver tumors.

PURPOSE: To 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. 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 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 . 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 kPL and under-flipped regions overestimated kPL . B1+ correction addressed this issue. CONCLUSION: The 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.

Modeling hyperpolarized lactate signal dynamics in cells, patient-derived tissue slice cultures and murine models.

Determining the aggressiveness of renal cell carcinoma (RCC) noninvasively is a critical part of the diagnostic workup for treating this disease that kills more than 15,000 people annually in the USA. Recently, we have shown that not only the amount of lactate produced, as a consequence of the Warburg effect, but also its efflux out of the cell, is a critical marker of RCC aggressiveness and differentiating RCCs from benign renal tumors. Enzymatic conversions can now be measured in situ with hyperpolarized (HP) 13 C magnetic resonance (MR) on a sub-minute time scale. Using RCC models, we have shown that this technology can interrogate in real time both lactate production and compartmentalization, which are associated with tumor aggressiveness. The dynamic HP MR data have enabled us to robustly characterize parameters that have been elusive to measure directly in intact living cells and murine tumors thus far. Specifically, we were able to measure the same intracellular lactate longitudinal relaxation time in three RCC cell lines of 16.42 s, and lactate efflux rate ranging from 0.14 to 0.8 s-1 in the least to the most aggressive RCC cell lines and correlate it to monocarboxylate transporter isoform 4 expression. We also analyzed dynamic HP lactate and pyruvate data from orthotopic murine RCC tumors using a simplified one-compartment model, and showed comparable apparent pyruvate to lactate conversion rate (kPL ) values with those measured in vitro. This kinetic modeling was then extended to characterize the lactate dynamics in patient-derived living RCC tissue slices; and even without direct measurement of the extracellular lactate signal the efflux parameter was still assessed and was distinct between the benign renal tumors and RCCs. Across all these preclinical models, the rate parameters of kPL and lactate efflux correlated to cancer aggressiveness, demonstrating the validity of our modeling approach for noninvasive assessment of RCC aggressiveness.

Improved Sensitivity and Reader Confidence in CT Colonography Using Dual-Layer Spectral CT: A Phantom Study.

Background Limited cathartic preparations for CT colonography with fecal tagging can improve patient comfort but may result in nondiagnostic examinations from poorly tagged stool. Dual-energy CT may overcome this limitation by improving the conspicuity of the contrast agent, but more data are needed. Purpose To investigate whether dual-energy CT improves polyp detection in CT colonography compared with conventional CT at different fecal tagging levels in vitro. Materials and Methods In this HIPAA-compliant study, between December 2017 and August 2019, a colon phantom 30 cm in diameter containing 60 polyps of different shapes (spherical, ellipsoid, flat) and size groups (5-9 mm, 11-15 mm) was constructed and serially filled with simulated feces tagged with four different iodine concentrations (1.26, 2.45, 4.88, and 21.00 mg of iodine per milliliter), then it was scanned with dual-energy CT with and without an outer fat ring to simulate large body size (total diameter, 42 cm). Two readers independently reviewed conventional 120-kVp CT and 40-keV monoenergetic dual-energy CT images to record the presence of polyps and confidence (three-point scale.) Generalized estimating equations were used for sensitivity comparisons between conventional CT and dual-energy CT, and a Wilcoxon signed-rank test was used for reader confidence. Results Dual-energy CT had higher overall sensitivity for polyp detection than conventional CT (58.8%; 95% confidence interval [CI]: 49.7%, 67.3%; 564 of 960 polyps vs 42.1%; 95% CI: 32.1%, 52.8%; 404 of 960 polyps; P < .001), including with the fat ring (48% and 31%, P < .001). Reader confidence improved with dual-energy CT compared with conventional images on all tagging levels (P < .001). Interrater agreement was substantial (κ = 0.74; 95% CI: 0.70, 0.77). Conclusion Compared with conventional 120-kVp CT, dual-energy CT improved polyp detection and reader confidence in a dedicated dual-energy CT colonography phantom, especially with suboptimal fecal tagging. © RSNA, 2020.

Estimation of Fractional Extracellular Space at CT for Predicting Chemotherapy Response and Survival in Pancreatic Ductal Adenocarcinoma.

OBJECTIVE. The purpose of this study was to investigate the association between primary pancreatic ductal adenocarcinoma fractional extracellular space (fECS) estimated from pretreatment CT and tumor response to chemotherapy and patient outcome. MATERIALS AND METHODS. A database search identified the records of patients with locally advanced or metastatic pancreatic ductal adenocarcinoma treated with systemic therapies who had undergone pretreatment CT that included both unenhanced and equilibrium phase images. An ROI was placed on the primary tumor and aorta, and the tumor fECS was calculated as follows: (tumor attenuation in the equilibrium phase - tumor attenuation in the unenhanced phase) / (aortic attenuation in the equilibrium phase - aortic attenuation in the unenhanced phase) × (1 - hematocrit). Response to therapy was assessed in subsequent CT examinations according to the Response Evaluation Criteria in Solid Tumors version 1.1. Relevant clinical variables, including carbohydrate antigen 19-9 level, chemotherapy regimen, and survival were recorded. Multivariate analyses were performed to determine the predictors of treatment response and patient survival. RESULTS. The median primary tumor fECS was 0.41 (range, 0.02-0.69). When dichotomized to high (> 0.41) versus low fECS (≤ 0.41) values, a larger proportion of patients with high tumor fECS values achieved disease control after chemotherapy than did those with low tumor fECS values: full cohort, 27 of 30 versus 19 of 30 (p = 0.030); cohort with locally advanced disease, 23 of 24 versus 10 of 15 (p = 0.024). The mean progression-free survival among patients with high primary tumor fECS values was significantly longer than that among those with low fECS values (191 versus 115 days, p = < 0.0001). Primary tumor fECS was an independent predictor of progression-free survival (p = 0.003) in multivariate analysis. CONCLUSION. High primary tumor fECS value estimated from staging CT was associated with chemotherapy response and progression-free survival of patients with advanced pancreatic ductal adenocarcinoma.

Consensus-based technical recommendations for clinical translation of renal BOLD MRI.

Harmonization of acquisition and analysis protocols is an important step in the validation of BOLD MRI as a renal biomarker. This harmonization initiative provides technical recommendations based on a consensus report with the aim to move towards standardized protocols that facilitate clinical translation and comparison of data across sites. We used a recently published systematic review paper, which included a detailed summary of renal BOLD MRI technical parameters and areas of investigation in its supplementary material, as the starting point in developing the survey questionnaires for seeking consensus. Survey data were collected via the Delphi consensus process from 24 researchers on renal BOLD MRI exam preparation, data acquisition, data analysis, and interpretation. Consensus was defined as ≥ 75% unanimity in response. Among 31 survey questions, 14 achieved consensus resolution, 12 showed clear respondent preference (65-74% agreement), and 5 showed equal (50/50%) split in opinion among respondents. Recommendations for subject preparation, data acquisition, processing and reporting are given based on the survey results and review of the literature. These technical recommendations are aimed towards increased inter-site harmonization, a first step towards standardization of renal BOLD MRI protocols across sites. We expect this to be an iterative process updated dynamically based on progress in the field.

Hyperpolarized 13C MRI: State of the Art and Future Directions.

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.

Bosniak Classification of Cystic Renal Masses, Version 2019: An Update Proposal and Needs Assessment.

Cystic renal cell carcinoma (RCC) is almost certainly overdiagnosed and overtreated. Efforts to diagnose and treat RCC at a curable stage result in many benign neoplasms and indolent cancers being resected without clear benefit. This is especially true for cystic masses, which compared with solid masses are more likely to be benign and, when malignant, less aggressive. For more than 30 years, the Bosniak classification has been used to stratify the risk of malignancy in cystic renal masses. Although it is widely used and still effective, the classification does not formally incorporate masses identified at MRI or US or masses that are incompletely characterized but are highly likely to be benign, and it is affected by interreader variability and variable reported malignancy rates. The Bosniak classification system cannot fully differentiate aggressive from indolent cancers and results in many benign masses being resected. This proposed update to the Bosniak classification addresses some of these shortcomings. The primary modifications incorporate MRI, establish definitions for previously vague imaging terms, and enable a greater proportion of masses to enter lower-risk classes. Although the update will require validation, it aims to expand the number of cystic masses to which the Bosniak classification can be applied while improving its precision and accuracy for the likelihood of cancer in each class.

Living Donor Liver Transplantation: Overview, Imaging Technique, and Diagnostic Considerations.

OBJECTIVE. The purpose of this article is to discuss the process of becoming a liver donor, describe the surgical methods used for transplantation, and critically review preoperative and intraoperative imaging techniques. CONCLUSION. Radiologists play a vital role in ensuring the safety of living liver donors; however, consensus guidelines do not exist for imaging protocol or reporting. Standardization would provide more consistent image quality across centers, improve communication with the transplant team, and facilitate data mining for quality assurance and research.

Living Donor Liver Transplantation: Preoperative Planning and Postoperative Complications.

OBJECTIVE. The purposes of this article are to highlight the similarities and differences in workup and work flow across multiple institutions in the preoperative imaging assessment of liver donors; to lay the foundation for developing consensus guidelines; to illustrate clinically relevant anatomic variants; to introduce a standardized reporting template; and to review postprocessing work flow and postoperative donor complications. CONCLUSION. Further investigation and consensus are needed to determine protocols, time intervals, and duration of follow-up of liver donors that are cost-effective and clinically relevant.

Abbreviated MRI Protocols for the Abdomen.

Technical advances in MRI have improved image quality and have led to expanding clinical indications for its use. However, long examination and interpretation times, as well as higher costs, still represent barriers to use of MRI. Abbreviated MRI protocols have emerged as an alternative to standard MRI protocols. These abbreviated MRI protocols seek to reduce longer MRI protocols by eliminating unnecessary or redundant sequences that negatively affect cost, MRI table time, patient comfort, image quality, and image interpretation time. However, the diagnostic information is generally not compromised. Abbreviated MRI protocols have already been used successfully for hepatocellular carcinoma screening, for prostate cancer detection, and for screening for nonalcoholic fatty liver disease as well as monitoring patients with this disease. It has been reported that image acquisition time and costs can be considerably reduced with abbreviated MRI protocols, compared with standard MRI protocols, while maintaining a similar sensitivity and accuracy. Nevertheless, multiple applications still need to be explored in the abdomen and pelvis (eg, surveillance of metastases to the liver; follow-up of cystic pancreatic lesions, adrenal incidentalomas, and small renal masses; evaluation of ovarian cysts in postmenopausal women; staging of cervical and uterine corpus neoplasms; evaluation of müllerian duct anomalies). This article describes some successful applications of abbreviated MRI protocols, demonstrates how they can help in improving the MRI workflow, and explores potential future directions. ©RSNA, 2019.

Direct assessment of renal mitochondrial redox state using hyperpolarized 13 C-acetoacetate.

PURPOSE: The purpose of this study was to investigate the hyperpolarized ketone body 13 C-acetoacetate (AcAc) and its conversion to 13 C-ß-hydroxybutyrate (ßOHB) in vivo, catalyzed by ß-hydroxybutyrate dehydrogenase (BDH), as a novel direct marker of mitochondrial redox state. METHODS: [1,3-13 C2 ]AcAc was synthesized by hydrolysis of the ethyl ester, and hyperpolarized via dissolution DNP. Cold storage under basic conditions resulted in sufficient chemical stability for use in hyperpolarized (HP) MRI studies. Polarizations and relaxation times of HP [1,3-13 C2 ]AcAc were measured in a clinical 3T MRI scanner, and 8 rats were scanned by dynamic HP 13 C MR spectroscopy of a slab through the kidneys. Four rats were scanned after acute treatment with high dose metformin (125 mg/kg, intravenous), which is known to modulate mitochondrial redox via inhibition of mitochondrial complex I. An additional metformin-treated rat was scanned by abdominal 2D CSI (8 mm × 8 mm). RESULTS: Polarizations of 7 ± 1% and 7 ± 3%, and T1 relaxation times of 58 ± 5 s and 52 ± 3 s, were attained at the C1 and C3 positions, respectively. Rapid conversion of HP AcAc to ßOHB was detected in rat kidney in vivo, via the C1 label. The product HP ßOHB was resolved from closely resonating acetate. Conversion to ßOHB was also detected via 2D CSI, in both kidney as well as liver regions. Metformin treatment resulted in a significant increase (40%, P = 0.01) of conversion of HP AcAc to ßOHB. CONCLUSION: Rapid conversion of HP AcAc to ßOHB was observed in rat kidney in vivo and is a promising new non-invasive marker of mitochondrial redox state. Magn Reson Med 79:1862-1869, 2018. © 2017 International Society for Magnetic Resonance in Medicine.