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Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related death in the United States and is projected to be the second by 2030. Systemic combination chemotherapy is considered an essential first-line treatment for the majority of patients with PDA, in both the neoadjuvant and palliative settings. In addition, a number of novel therapies are being tested in clinical trials for patients with advanced PDA. In all cases, accurate and timely assessment of treatment response is critical to guide therapy, reduce drug toxicities and cost from a failing therapy, and aid adaptive clinical trials. Conventional morphological imaging has significant limitations, especially in the context of determining primary tumor response and resectability following neoadjuvant therapies. In this article, we provide an overview of current therapy options for PDA, highlight several morphological imaging findings that may be helpful to reduce over-staging following neoadjuvant therapy, and discuss a number of emerging imaging, and non-imaging, tools that have shown promise in providing a more precise quantification of disease burden and treatment response in PDA.Graphic Abstract

To investigate the utility of dynamic contrast-enhanced MRI (DCE-MRI) with Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for detecting liver fibrosis induced by carbon tetrachloride (CCl4) in rats. This study was approved by the institutional animal care and use committee. Liver fibrosis in rats was induced by intraperitoneal injection of 1 mL/kg 50% CCl4 twice a week for 4-13 weeks. Control rats were injected with saline. Liver fibrosis was graded using the Metaviar score: no fibrosis (F0), mild fibrosis (F1-F2) and advanced fibrosis (F3-F4). DCE-MRI with Gd-EOB-DTPA was performed for all rats. Ktrans, Kep, Ve and iAUC of the liver parenchyma were measured. Relative enhancement (RE) value of the liver was calculated on T1-weighted images at 15, 20 and 25 min after Gd-EOB-DTPA administration. Thirty-five rats were included: no fibrosis (n=13), mild fibrosis (n=11) and advanced fibrosis (n=11). Ktrans and iAUC values were highest in advanced fibrosis group and lowest in no fibrosis group (P＜0.05). The area under the receiver operating characteristic curve (AUROC) for fibrosis (stages F1 and greater) were 0.773 and 0.882 for Ktrans and iAUC, respectively. AUROC for advanced fibrosis were 0.835 and 0.867 for Ktrans and iAUC, respectively. Kep and RE values were not able to differentiate fibrosis stages (all P＞0.05). Ktrans and iAUC obtained from DCE-MRI with Gd-EOB-DTPA are useful for the detection and staging of rat liver fibrosis induced by CCl4.

Purpose To investigate whether dynamic contrast -enhanced MRI (DCE-MRI) can distinguish the type of liver nodules in a rat model with N-nitrosodiethylamine- induced cirrhosis. Methods Liver nodules in cirrhosis were induced in 60 male Wistar rats via 0.01 % N-nitrosodiethylamine in the drinking water for 35-100 days. The nodules were divided into three groups: regenerative nodule (RN), dysplastic nodule (DN), and hepatocellular carcinoma (HCC). DCE-MRI was performed, and parameters including transfer constant (K trans ), rate constant (K ep ), extravascular extracellular space volume fraction (V e ), and initial area under the contrast concentration versus time curve (iAUC) were measured and compared. Results The highest K trans and iAUC values were seen in HCC, followed by DN and RN (all P  < 0.05). The area under the receiver operating characteristic curve (AUROC) for DN and HCC were 0.738 and 0.728 for K trans and iAUC, respectively. The AUROC for HCC were 0.850 and 0.840 for K trans and iAUC, respectively. Ordinal logistic regression analysis showed that K trans had a high goodness of fit (0.970, 95 % confidence interval, 13.751-24.958). Conclusion DCE-MRI is a promising method to differentiate of liver nodules. Elevated K trans suggested that the nodules may be transformed into HCC. Key points • DCE-MRI is promising for differentiating among RN, DN, and HCC • K trans and iAUC positively correlated with malignancy degree of liver nodules • Elevated K trans suggests that the nodules may be transformed into HCC

Purpose To investigate whether the addition of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced 3D T1-weighted MR cholangiography (T1w-MRC) to 3D T2-weighted MRC (T2w-MRC) improves the confidence and diagnostic accuracy of biliary anatomy in living liver donors. Methods Two abdominal radiologists retrospectively and independently reviewed pre-operative MR studies in 58 consecutive living liver donors. The second-order bile duct visualization on T1w- and T2w-MRC images was rated on a 4-point scale. The readers also independently recorded the biliary anatomy and their diagnostic confidence using (1) combined T1w- and T2w-MRC, and (2) T2w-MRC. In the 23 right lobe donors, the biliary anatomy at imaging and the imaging-predicted number of duct orifices at surgery were compared to intra-operative findings. Results T1w-MRC had a higher proportion of excellent visualization than T2w-MRC, 66% vs. 45% for reader 1 and 60% vs. 31% for reader 2. The median confidence score for biliary anatomy diagnosis was significantly higher with combined T1w- and T2w-MRC than T2w-MRC alone for both readers (Reader 1: 3 vs. 2, p  < 0.001; Reader 2: 3 vs. 1, p  < 0.001). Compared to intra-operative findings, the accuracy of imaging-predicted number of duct orifices using combined T1w-and T2w-MRC was significantly higher than that using T2w-MRC alone ( p  = 0.034 for reader 1, p  = 0.0082 for reader 2). Conclusion The addition of Gd-EOB-DTPA-enhanced 3D T1w-MRC to 3D T2w-MRC improves second-order bile duct visualization and increases the confidence in biliary anatomy diagnosis and the accuracy in the imaging-predicted number of duct orifices acquired during right lobe harvesting.

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

PurposeTo determine the need for a standardized renal mass reporting template by analyzing reports of indeterminate renal masses and comparing their contents to stated preferences of radiologists and urologists.MethodsThe host IRB waived regulatory oversight for this multi-institutional HIPAA-compliant quality improvement effort. CT and MRI reports created to characterize an indeterminate renal mass were analyzed from 6 community (median: 17 reports/site) and 6 academic (median: 23 reports/site) United States practices. Report contents were compared to a published national survey of stated preferences by academic radiologists and urologists from 9 institutions. Descriptive statistics and Chi-square tests were calculated.ResultsOf 319 reports, 85% (271; 192 CT, 79 MRI) reported a possibly malignant mass (236 solid, 35 cystic). Some essential elements were commonly described: size (99% [269/271]), mass type (solid vs. cystic; 99% [268/271]), enhancement (presence vs. absence; 92% [248/271]). Other essential elements had incomplete penetrance: the presence or absence of fat in solid masses (14% [34/236]), size comparisons when available (79% [111/140]), Bosniak classification for cystic masses (54% [19/35]). Preferred but non-essential elements generally were described in less than half of reports. Nephrometry scores usually were not included for local therapy candidates (12% [30/257]). Academic practices were significantly more likely than community practices to include mass characterization details, probability of malignancy, and staging. Community practices were significantly more likely to include management recommendations.ConclusionsRenal mass reporting elements considered essential or preferred often are omitted in radiology reports. Variation exists across radiologists and practice settings. A standardized template may mitigate these inconsistencies.

Nonalcoholic fatty liver disease (NAFLD) has become highly prevalent, now considered the most common liver disease in the western world. Approximately one-third of patients with NASH develop non-alchoholic steatohepatitis (NASH), histologically defined by lobular and portal inflammation, and accompanied by marked oxidative stress. Patients with NASH are at increased risk for cirrhosis and hepatocellular carcinoma, and diagnosis currently requires invasive biopsy. In animal models of NASH, particularly the methionine-choline deficient (MCD) model, profound changes are seen in redox enzymes and key intracellular antioxidants. To study antioxidant status in NASH non-invasively, we applied the redox probe hyperpolarized [1- 13 C] dehydroascorbic acid (HP DHA), which is reduced to Vitamin C (VitC) rapidly in the normal liver. In MCD mice, we observed a significant decrease in HP DHA to VitC conversion that accompanied hepatic fat deposition. When these animals were subsequently placed on a normal diet, resonance ratios reverted to those seen in control mice. These findings suggest that HP DHA, a potentially clinically translatable imaging agent, holds special promise in imaging NASH and other metabolic syndromes, to monitor disease progression and response to targeted therapies.

Desmoplasia describes the deposition of extensive extracellular matrix and defines primary pancreatic ductal adenocarcinoma (PDA). The acellular component of this stroma has been implicated in PDA pathogenesis and is being targeted therapeutically in clinical trials. By analyzing the stromal content of PDA samples from numerous annotated PDA data sets and correlating stromal content with both anatomic site and clinical outcome, we found PDA metastases in the liver, the primary cause of mortality to have less stroma, have higher tumor cellularity than primary tumors. Experimentally manipulating stromal matrix with an anti-lysyl oxidase like-2 (anti-LOXL2) antibody in syngeneic orthotopic PDA mouse models significantly decreased matrix content, led to lower tissue stiffness, lower contrast retention on computed tomography, and accelerated tumor growth, resulting in diminished overall survival. These studies suggest an important protective role of stroma in PDA and urge caution in clinically deploying stromal depletion strategies.

Purpose: To assess the influence of different dual-energy CT (DECT) scanner techniques on the severity of visceral-motion-related artifacts on the liver. Methods: Two independent readers retrospectively evaluated visceral-motion-related artifacts on the liver on 120-kVp(-like), monoenergetic low- and high-keV, virtual non-contrast (VNC), and iodine images acquired on a dual-source, twin-beam, fast kV-switching, and dual-layer spectral detector scanner. Quantitative assessment: Depth of artifact extension into the liver, measurements of Hounsfield Units (HU) and iodine concentrations. Qualitative assessment: Five-point Likert scale (1 = none to 5 = severe). Artifact severity between image reconstructions were compared by Wilcoxon signed-rank and paired t-tests. Results: 615 contrast-enhanced routine clinical DECT scans of the abdomen were evaluated in 458 consecutive patients (mean age: 61 ± 14 years, 331 men). For dual-source and twin-beam scanners, depth of extension of artifacts into the liver was significantly shorter and artifact severity scores significantly lower for 120-kVp-like images compared with the other image reconstructions (p < 0.001, each). For fast kV-switching and spectral detector scanner images, depth of extension of artifacts was significantly shorter and artifact severity scores significantly lower for iodine images (p < 0.001, each). Dual-source 120-kVp-like and spectral detector iodine images reduced artifacts to an extent that no significant difference in HU or iodine concentrations between artifacts (dual-source: 97 HU, spectral detector: 1.9 mg/mL) and unaffected liver parenchyma (dual-source: 108 HU, spectral detector: 2.1 mg/mL) was measurable (dual-source: p = 0.32, spectral detector: p = 0.15). Conclusion: Visceral-motion-related artifacts on the liver can be markedly reduced by viewing 120-kVp-like images for dual-source and twin-beam DECT scanners and iodine images for fast kV-switching and dual-layer spectral detector DECT scanners.

Background: Peristalsis-related streak artifacts on the liver compromise image quality and diagnostic accuracy. Purpose: To assess dual-layer spectral-detector computed tomography (CT) image reconstructions for reducing intestinal peristalsis-related streak artifacts on the liver. Methods: We retrospectively evaluated 220 contrast-enhanced abdominal dual-energy CT scans in 131 consecutive patients (mean age: 68 ± 10 years, 120 men) who underwent routine clinical dual-layer spectral-detector CT imaging (120 kVp, 40 keV, 200 keV, virtual non-contrast (VNC), iodine images). Two independent readers evaluated bowel peristalsis streak artifacts on the liver qualitatively on a five-point Likert scale (1 = none to 5 = severe) and quantitatively by depth of streak artifact extension into the liver and measurements of Hounsfield Unit and iodine concentration differences from normal liver. Artifact severity between image reconstructions were compared by Wilcoxon signed-rank and paired t-tests. Results: 12 scans were excluded due to missing spectral data, artifacts on the liver originating from metallic foreign materials, or oral contrast material. Streak artifacts on the liver were seen in 51/208 (25%) scans and involved the left lobe only in 49/51 (96%), the right lobe only in 0/51 (0%), and both lobes in 2/51 (4%) scans. Artifact frequency was lower in iodine than in 120 kVp images (scans 18/208 vs. 51/208, p < 0.001). Artifact severity was less in iodine than in 120 kVp images (median score 1 vs. 3, p < 0.001). Streak artifact extension into the liver was shorter in iodine than 120 kVp images (mean length 2 ± 4 vs. 12 ± 5 mm, p < 0.001). Hounsfield Unit and iodine concentration differed significantly between bright streak artifacts and normal liver in 120 kVp, 40 keV, 200 keV, and VNC images (p < 0.001, each), but not in iodine images (p = 0.23). Conclusion: Intestinal peristalsis-related streak artifacts commonly affect the left liver lobe at CT and can be substantially reduced by viewing iodine dual-energy CT image reconstructions.