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OBJECTIVE This study aimed to assess the diagnostic accuracy of magnetic resonance elastography (MRE) in detecting hepatic fibrosis and determining clinically relevant stiffness cutoff values per stage of fibrosis. METHODS This retrospective study assessed 1488 hepatic MRE evaluations performed at a single institution for 5 years. Mean liver stiffness measurements were collected from 282 patients who had an MRE study within 1 year of histopathologic analysis. Areas under receiver operating characteristic curves were calculated for each stage of fibrosis with nonparametric ordinal measures of accuracy, and Youden Index was determined. RESULTS Mean liver stiffness measurement values were as follows: F0, 2.5± 0.55 kPa; F1, 3.1± 0.80 kPa; F2, 3.4±0.95 kPa; F3, 4.7±1.44 kPa; and F4, 7.9± 2.64 kPa. Nonparametric ordinal measures of accuracy per fibrosis stage were as follows: F0: 0.934, P < 0.001; F0-F1: 0.917, P < 0.001; F0-F2: 0.944, P < 0.001; and F0-F3: 0.941, P < 0.001. Youden Index values for fibrosis stages F2, F3, and F4 were 3.9, 4.0, and 4.5 kPa, respectively. CONCLUSIONS Magnetic resonance elastography is an accurate diagnostic tool in assessing liver fibrosis.

Vascular invasion by hepatocellular carcinoma (HCC), also known as tumor in vein (TIV), indicates highly invasive tumor behavior and is also associated with poor outcome. Because a diagnosis of TIV precludes liver transplantation, knowledge of the imaging findings to differentiate between TIV and bland thrombus is key for proper patient management. Prior versions of liver imaging reporting and data system (LI-RADS) included presence of TIV as part of LR-5 criteria. However, even if HCC is the most common liver malignancy associated with TIV, other tumors can have vascular invasion and may occur in cirrhotic patients. For these reasons, in LI-RADS v2017 LR-TIV has been introduced as a new different diagnostic category. The aim of this article is to discuss the diagnostic criteria of LR-TIV according to LI-RADS v2018 and analyze potential pitfalls encountered on daily clinical practice. Indeterminate cases and how to manage them will also be discussed.

Obesity is a global pandemic that is causally linked to many life-threatening diseases. Apart from some rare genetic conditions, the biological drivers of overeating and reduced activity are unclear. Here, we show that neurotensin-expressing neurons in the mouse IPAC, a nucleus of the central extended amygdala, encode dietary preference for unhealthy energy-dense foods. Optogenetic activation of IPAC(Nts) neurons promotes obesogenic behaviors, such as hedonic eating, and modulates food preference. Conversely, acute inhibition of IPAC(Nts) neurons reduces feeding and decreases hedonic eating. Chronic inactivation of IPAC(Nts) neurons recapitulates these effects, reduces preference for sweet, non-caloric tastants, and, furthermore, enhances locomotion and energy expenditure. As a result, mice display long-term weight loss, improved metabolic health, and are protected from obesity. Thus, the activity of a single neuronal population bidirectionally regulates energy homeostasis. Our findings could lead to new therapeutic strategies to prevent and treat obesity.

The mammalian brain develops through a complex interplay of spatial cues generated by diffusible morphogens, cell–cell interactions and intrinsic genetic programs that result in probably more than a thousand distinct cell types. A complete understanding of this process requires a systematic characterization of cell states over the entire spatiotemporal range of brain development. The ability of single-cell RNA sequencing and spatial transcriptomics to reveal the molecular heterogeneity of complex tissues has therefore been particularly powerful in the nervous system. Previous studies have explored development in specific brain regions1–8, the whole adult brain9 and even entire embryos10. Here we report a comprehensive single-cell transcriptomic atlas of the embryonic mouse brain between gastrulation and birth. We identified almost eight hundred cellular states that describe a developmental program for the functional elements of the brain and its enclosing membranes, including the early neuroepithelium, region-specific secondary organizers, and both neurogenic and gliogenic progenitors. We also used in situ mRNA sequencing to map the spatial expression patterns of key developmental genes. Integrating the in situ data with our single-cell clusters revealed the precise spatial organization of neural progenitors during the patterning of the nervous system. A comprehensive single-cell transcriptomic atlas of the mouse brain between gastrulation and birth identifies hundreds of cellular states and reveals the spatiotemporal organization of brain development.

The increasingly favorable outcomes of live donor liver transplant warrant development of screening techniques to expand current donor pool. Transient elastography (TE) with controlled attenuation parameter (CAP) is accessible and has promising diagnostic performance in non-obese individuals. Here, we demonstrate its utility in grading donor steatosis for risk assessment in living liver donors (LLD).In a prospective study of LLD and recipients, accuracy was determined using MRI-derived proton density fat fraction (PDFF) as reference.One hundred and one LLD underwent TE, 95 of whom had available PDFF. Median CAP and MRI-PDFF were 233 dB/m (206-270) and 2.9% (2.3-4.0), respectively. A CAP threshold of 270 dB/m captured all steatosis which was present in 13 (13%) LLD (AUROC .942, 100% sensitivity and 83% specificity). Performance further improved when excluding obese LLD and limiting analysis to M-probe (AUROC .971 and .974, respectively, with 87% specificity). There was no difference in CAP and MRI-PDFF between LLD and nondonors (P = .26 and .21, respectively). Early allograft dysfunction was observed in one recipient (CAP 316, PDFF 9.5%), zero underwent retransplant, and one died from sepsis.The specific role of CAP in living liver donation warrants further study, beginning with its use as screening tool across peripheral clinics.

To evaluate targetoid appearance on T2-weighted imaging and signs of tumor vascular involvement as potential new LI-RADS features for differentiating hepatocellular carcinoma (HCC) from other non-HCC primary liver carcinomas (PLCs). This IRB-approved, retrospective study was performed at two liver transplant centers. The final population included 375 patients with pathologically proven lesions imaged between 2007 and 2017 with contrast-enhanced CT or MRI. The cohort consisted of 165 intrahepatic cholangiocarcinomas and 74 combined hepatocellular-cholangiocarcinomas, with the addition of 136 HCCs for control. Two abdominal radiologists (R1; R2) independently reviewed the imaging studies (112 CT; 263 MRI) and recorded the presence of targetoid appearance on T2-weighted images and features of tumor vascular involvement including encasement, narrowing, tethering, occlusion, and obliteration. The sensitivity and specificity of each feature were calculated for the diagnosis of non-HCC PLCs. Cohen’s kappa (k) test was used to assess inter-reader agreement. The sensitivity of targetoid appearance on T2-weighted images for the diagnosis of non-HCC PLCs was 27.5% and 32.6% (R1 and R2) and the specificity was 98.2% and 97.3% (R1 and R2). Among the features of tumor vascular involvement, those providing the highest sensitivity for non-HCC PLCs were vascular encasement (R1: 34.3%; R2: 37.2%) and obliteration (R1: 25.5%; R2: 29.7%). The highest specificity for non-HCC PLCs was provided by tethering (R1: 100%; R2: 97.1%) and occlusion (R1: 99.3%; R2: 99.3%). The inter-reader agreement was moderate to substantial (k = 0.48–0.77). Targetoid appearance on T2-weighted images and features of tumor vascular involvement demonstrated high specificity for non-HCC malignancy. • Targetoid appearance on T2-weighted imaging and signs of tumor vascular involvement have high specificity (92–100%) for the diagnosis of non-HCC PLCs, regardless of the presence of liver risk factors. • In the subset of patients with risk factors for HCC, the sensitivity of signs of tumor vascular involvement decreases for both readers (1.7–20.3%), while the specificity increases reaching values higher than 94.2%. • The inter-reader agreement is substantial for targetoid appearance on T2-weighted images (k = 0.74) and moderate to substantial for signs of tumor vascular involvement (k = 0.48–0.77).

To identify clinical and imaging biomarkers that can predict the new onset of diabetes mellitus (NODM) within 1 year of pancreatic resection. A retrospective chart review was conducted of 426 non-diabetic patients who underwent a pancreaticoduodenectomy or distal pancreatectomy at the University of Pittsburgh Medical Center between 2006 and 2016. Clinical characteristics and the patient’s diabetic status at 1-year post resection were collected from the EMR. Imaging biomarkers included hepatic and pancreatic fat replacement, pancreatic calcifications, pancreatic duct diameter, pancreatic volume and body composition. Univariate and multivariable analyses were performed to demonstrate any predictive biomarkers of diabetes occurrence within 1 year of pancreatic resection. 135/426 (31.7%) patients developed NODM. The only significant clinical predictor was older age (OR 1.02, 95% CI 1.002–1.039, p = 0.032). Imaging characteristics found to be significant included hepatic steatosis (OR 1.777, 95% CI 1.094–2.886, p = 0.02), larger reduction in pancreas volume (OR 0.989, 95% CI 0.979–0.999, p = 0.027), and greater preoperative visceral fat (OR 1.004, 95% CI 1.001–1.006, p = 0.001). Age, presence of hepatic steatosis, change in pancreatic volume, and preoperative visceral fat are independent predictive biomarkers for NODM following pancreatic resection.

Infiltrative-appearance hepatocellular carcinoma presents a challenge to clinicians as diagnostic criteria continue to evolve and evidence-based treatment guidelines have yet to be established. While transarterial radioembolization has shown efficacy in hepatocellular carcinoma, many studies exclude infiltrative-appearance HCC in their analysis. The purpose of this study was to describe imaging features of infiltrative-appearance hepatocellular carcinoma and evaluate effects of radioembolization on survival. In a retrospective review, infiltrative HCC patients treated from 2008 to 2017 were identified. Patients were divided into two groups: TARE versus systemic therapy/palliative care. Demographics, dates of diagnosis/expiry, albumin, international normalized ratio (INR), sodium, alpha-fetoprotein (AFP), creatinine, Child-Pugh class, model for end-stage liver disease (MELD) score, bilirubin, radiation dose and volume were collected. Patients with bilirubin > 3 were excluded. Mann–Whitney U test and Fisher’s exact test assessed differences between groups. Kaplan–Meier survival and Cox proportional hazard analyses were performed. Fifty-three patients were identified, 15 underwent TARE while 38 served as control. Mean age was 60, 43 patients were male. The mean overall survival was 16.2 months for the TARE group and 5.3 months for the control group (Log-rank p

The central amygdala (CeA) is critically involved in a range of adaptive behaviors, including defensive behaviors. Neurons in the CeA send long-range projections to a number of extra-amygdala targets, but the functions of these projections remain elusive. Here, we report that a previously neglected CeA-to-globus pallidus external segment (GPe) circuit plays an essential role in classical fear conditioning. By anatomic tracing,in situhybridization and channelrhodopsin (ChR2)-assisted circuit mapping in both male and female mice, we found that a subset of CeA neurons send projections to the GPe, and the majority of these GPe-projecting CeA neurons express the neuropeptide somatostatin. Notably, chronic inhibition of GPe-projecting CeA neurons with the tetanus toxin light chain (TeLC) completely blocks auditory fear conditioning.In vivofiber photometry revealed that these neurons are selectively excited by the unconditioned stimulus (US) during fear conditioning. Furthermore, transient optogenetic inactivation or activation of these neurons selectively during US presentation impairs or promotes, respectively, fear learning. Our results suggest that a major function of GPe-projecting CeA neurons is to represent and convey US-related information through the CeA-GPe circuit, thereby regulating learning in fear conditioning.SIGNIFICANCE STATEMENTThe central amygdala (CeA) has been implicated in the establishment of defensive behaviors toward threats, but the underlying circuit mechanisms remain unclear. Here, we found that a subpopulation of neurons in the CeA, which are mainly those that express the neuropeptide somatostatin, send projections to the globus pallidus external segment (GPe), and this CeA-GPe circuit conveys unconditioned stimulus (US)-related information during classical fear conditioning, thereby having an indispensable role in learning. Our results reveal a previously unknown circuit mechanism for fear learning.

To assess the accuracy of MRI-derived liver surface nodularity (LSN) score for staging of hepatic fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Forty-seven patients with clinicopathological diagnosis of NAFLD who underwent 1.5-T liver MRI within 12 months of liver biopsy were included. Axial non-contrast T1-weighted 3D GRE was used for image analysis. LSN of the left lobe was measured using a custom semiautomated software. Histopathologic analysis (F0–F4) served as the reference standard for staging of fibrosis. Mann-Whitney test and Spearman’s correlation coefficient were used to compare LSN scores between different stages of fibrosis and to assess the correlation. Diagnostic performance of LSN score for detection of significant (F2–F4) and advanced (F3–F4) fibrosis was assessed by receiver operating characteristics (ROC) curve. p value of less than 0.05 was considered statistically significant different. Twenty-one subjects had advanced fibrosis. The LSN scores among different stages of fibrosis were significantly different (p

Multiparametric MR provides a noninvasive means for improved differentiation between benign and malignant solid renal masses. Although most large, heterogeneous renal masses are due to renal cell carcinoma, smaller "indeterminate" renal masses are being identified on cross-sectional imaging. Although definitive diagnosis of a solid renal mass may not always be possible by MR imaging, integrated evaluation of multiple MR imaging parameters can result in concise differential diagnosis. Multiparametric MR should be considered a critical step in the triage of patients with a solid renal mass for whom treatment options are being considered in the context of morbidity, prognosis, and mortality.

We report our PET/MRI experience from a pilot study that compared the diagnostic performance of 18F-FDG PET/MRI versus PET/CT in staging of cervical cancer. Methods: Six adults with newly diagnosed cervical cancer underwent a single 18F-FDG injection with a dual-imaging protocol: standard-of-care PET/CT followed by research PET/MRI. The diagnostic interpretation and SUVmax for the 2 modalities were compared. Results: Both modalities detected all primary tumors (median size, 3.9 cm) and all 4 metastases present in 2 of the 6 patients (median size, 0.9 cm). PET/MRI provided greater diagnostic confidence than PET/CT and upstaged the disease in 4 patients. On the basis of the imaging findings alone, the additional information from PET/MRI would have led to a change in clinical management in 3 of 6 patients. The primary lesion showed a median SUV of 12.8 on PET/CT and 18.2 on PET/MRI (P = 0.03). SUVs, however, correlated strongly between the 2 modalities (ρ = 0.96, P

Neuroendocrine tumors (NETs) constitute a variety of neoplastic entities and exhibit variable degrees of neuroendocrine differentiation and phenotypes, as well as genetic profiles. Ga-DOTATATE PET is a novel imaging technique for NET. Although PET/CT is commonly utilized for oncologic imaging, PET/MRI is particularly suited for NETs, as MRI provides greater soft tissue contrast than CT, allowing for improved detection and characterization of NETs, particularly when liver metastasis is suspected or needs to be ruled out. The current pictorial review aims to illustrate the complementary advantages, as well as pitfalls of Ga-DOTATATE PET/MRI in the evaluation of NETs.

Background and aims Liver fibrosis results from cycles of liver damage and scar formation. We herein aimed at analysing neural crest cells and/or bone marrow stromal cells contribution to the liver. Methods Two liver fibrosis and one hepatectomy model were applied on double-transgenic loxP-Cre mouse lines. Results Increased numbers of glia with more complex processes were found in fibrotic livers. During embryonic development, only few cells were traced in the liver and bone marrow, in a minor fraction of mice of different neural crest reporter strains analysed: therefore, a neural crest origin of such cells is doubtful. In the fibrotic liver, a significantly higher incidence of endothelial cells and hepatocyte-like cells expressing the reporter gene Tomato were found in Wnt1-Cre-Tom and GLAST-CreERT2-Tom mice. Consistently, during early fibrogenesis stromal Wnt1-traced cells, with progenitor (CFU-F) properties, get likely mobilized to peripheral blood. Circulating adult Wnt1-traced cells are stromal cells and lack from the expression of other bone marrow and endothelial progenitor cells markers. Furthermore, in a 70% hepatectomy model GLAST+ Wnt1-traced pericytes were found to be mobilized from the bone marrow and the incidence of GLAST-traced hepatocyte-like cells was increased. Finally, GLAST-traced hepatocyte like-cells were found to maintain the expression of stromal markers. Conclusions Our data suggest a gliosis process during liver fibrogenesis. While neural crest cells probably do not contribute with other liver cell types than glia, GLAST+ Wnt1-traced bone marrow pericytes are likely a source of endothelial and hepatocyte-like cells after liver injury and do not contribute to scarring.

Background Multiparametric magnetic resonance imaging (mpMRI) may improve prostate cancer risk stratification and decrease the need for repeat biopsies in men on prostate cancer active surveillance (AS). However, the impact of mpMRI on AS-related healthcare spending has not been established. Objective To characterize the impact of mpMRI on AS-related Medicare expenditures. Design, setting, and participants Using Surveillance, Epidemiology, and End Results (SEER)-Medicare files, we identified men ≥66 yr old with localized prostate cancer diagnosed during 2008–2013. Outcome measures and statistical analysis With a validated algorithm, we classified men into AS with and without mpMRI groups. We then determined Medicare spending on AS in each group using inflation-adjusted, price-standardized Medicare payments for AS-related procedures (ie, prostate-specific antigen [PSA] tests, prostate biopsies, biopsy complications, and mpMRI). Multivariable median regression compared Medicare spending on AS for men who received mpMRI and those who did not. Results and limitations We identified 9081 men on AS with a median follow-up of 45 mo (interquartile range 29–64 mo). Thirteen percent (N = 1225) received mpMRI. On multivariable median regression, receipt of mpMRI was associated with an additional $447 (95% confidence interval $409–487) in Medicare spending per year. We observed greater frequency of AS-related procedures and higher spending for identical procedures (eg, PSA or prostate biopsy) in the mpMRI group than in the non-mpMRI group (all p Conclusions Among Medicare beneficiaries on AS, mpMRI is associated with additional annual Medicare spending. Future studies are needed to determine optimal use of mpMRI during AS to maximize value. Patient summary Prostate magnetic resonance imaging (MRI) helps physicians determine which prostate cancers are aggressive and which can be monitored safely. We studied whether using MRI during prostate cancer monitoring (also called active surveillance) resulted in increased healthcare spending. There was a modest increase in spending, but this may be worthwhile if the use of MRI allows physicians to monitor prostate cancer more accurately.

The article describes and illustrates the surgical techniques and the post-operative imaging anatomy in liver transplantation. Special attention is paid to the variant vascular and biliary anatomy that are important for surgical planning. Considering the ever-growing number of liver transplants performed and the key role that imaging plays in the pre-operative planning and post-operative assessment, it is important for the radiologist to be familiar with the surgical techniques and the normal post-operative appearance in these patients.

Multi-parametric prostate MRI (mpMRI) plays a critical role in the diagnosis, staging, and evaluation of treatment response in patients with prostate cancer. Radiologists, through an accurate and standardized interpretation of mpMRI, can clinically stage prostate cancer and help to risk stratify patients who may benefit from more invasive treatment or exclude patients who may be harmed by overtreatment. The purpose of this article is to describe key findings to accurately stage prostate cancer with mpMRI and to describe the contexts in which mpMRI is best applied.

A wide spectrum of pathologies, ranging from inconsequential degenerative and senile changes to clinically significant neoplasms, can affect seminal vesicles (SVs). With rapid rise in use of magnetic resonance imaging for evaluation of prostate in recent years an increasing number of cases of incidental SV pathologies are encountered by radiologists. Despite the high contrast resolution and high spatial resolution offered by multiparametric pelvic MRI, accurate diagnosis of SV processes can at times be challenging. In this article, we review the anatomy and embryology of the SVs and vasa deferentia and then explore the spectrum of diseases affecting them.

OBJECTIVE. The aim of the present study was to compare the diagnostic accuracy of liver stiffness measurements (LSMs) obtained using MR elastography (MRE), transient elastography (TE), and 2D shear wave elastography (SWE) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). SUBJECTS AND METHODS. We prospectively enrolled 62 adult subjects (mean age [± SD], 50 ± 13 years; 58% women; body mass index [weight in kilograms divided by the square of height in meters], 35 ± 7). Two-dimensional SWE, MRE, and TE were performed at a mean of 105 ± 86 days after liver biopsy. The area under the ROC curve (AUROC) values and 95% CIs for the corresponding LSMs (expressed in kilopascals) were calculated, with significant fibrosis (Metavir liver fibrosis score, F2-F4) and advanced fibrosis (F3-F4) used as outcome measures. Pairwise comparisons of AUROC values were conducted using the DeLong test. Statistical significance was set at p < 0.05. RESULTS. For the 62 subjects, valid LSMs were obtained for 57 subjects with the use of 2D SWE, for 59 subjects with TE, for 59 subjects with MRE, and for 54 subjects with all three modalities combined. The AUROC values (95% CIs) of 2D SWE, TE, and MRE for the diagnosis of significant fibrosis were 0.80 (0.67-0.92), 0.77 (0.64-0.89), and 0.85 (0.74-0.95), respectively. The AUROC values (95% CIs) of 2D SWE, TE, and MRE for the diagnosis of advanced fibrosis were 0.89 (0.80-0.98), 0.86 (0.77-0.95), and 0.95 (0.89-1.00), respectively. Pairwise comparisons revealed similar diagnostic accuracy for significant fibrosis (2D SWE vs MRE, p = 0.431; 2D SWE vs TE, p = 0.317; and MRE vs TE, p = 0.052) and advanced fibrosis (2D SWE vs MRE, p = 0.348; 2D SWE vs TE, p = 0.293; and MRE vs TE, p = 0.059). CONCLUSION. For patients with biopsy-proven NAFLD, 2D SWE, MRE and TE exhibited comparable and very good to excellent diagnostic accuracy for advanced fibrosis and comparable but lower accuracy for significant fibrosis.

Purpose Nodular regenerative hyperplasia (NRH) may mimic cirrhosis at imaging. We aim to investigate the effect of NRH on liver stiffness measurement (LSM) obtained with magnetic resonance elastography (MRE).Methods This retrospective, Institutional Review Board-approved study included 37 subjects with NRH (Group 1) and no or minimal fibrosis (F0-F1), a control group (Group 2) made of 30 subjects with non-advanced fibrosis (F0-F2), and a control group (Group 3) made of 30 subjects with advanced fibrosis (F3-F4), all with available MRE. LSM was measured in each subject along with assessment of hepatic morphological features of cirrhosis and signs of portal hypertension. The significance of the difference in mean LSM between Group 1 and 2 and between Group 1 and 3 was evaluated using the Mann-Whitney U test. The difference in distribution of imaging features among groups was assessed using the Pearson chi(2) or Fisher exact test.Results The mean +/- SD LSM in Group 1 (3.56 +/- 1.10 kPa) was significantly higher compared to Group 2 (2.91 +/- 0.52 kPa, P = 0.019) and significantly lower compared to Group 3 (7.18 +/- 2.08 kPa, P < 0.001). Twelve (32%) patients with NRH had LSM >= 4.11 kPa, and 6 (16%) patients had LSM >= 4.71 kPa. Surface nodularity (P = 0.032) and caudate lobe hypertrophy (P = 0.004) were more commonly visualized in Group 1 than in Group 2. At least one feature of portal hypertension was observed in 16 (43%) NRH subjects.Conclusion NRH may increase the LSM obtained with MRE and may represent a confounding factor when using liver stiffness for the non-invasive diagnosis of fibrosis.

PURPOSE: To reconstruct virtual MR elastography (MRE) images based on traditional MRI inputs with a machine learning algorithm. MATERIALS AND METHODS: In this single-institution, retrospective study, 149 patients (mean age, 58 years ± 12 [standard deviation]; 71 men) with nonalcoholic fatty liver disease who underwent MRI and MRE between January 2016 and January 2019 were evaluated. Nine conventional MRI sequences and clinical data were used to train a convolutional neural network to reconstruct MRE images at the per-voxel level. The architecture was further modified to accept multichannel three-dimensional inputs and to allow inclusion of clinical and demographic information. Liver stiffness and fibrosis category (F0 [no fibrosis] to F4 [significant fibrosis]) of reconstructed images were assessed by using voxel- and patient-level agreement by correlation, sensitivity, and specificity calculations; in addition, classification by receiver operator characteristic analyses was performed, and Dice score was used to evaluate hepatic stiffness locality. RESULTS: The model for predicting liver stiffness incorporated four image sequences (precontrast T1-weighted liver acquisition with volume acquisition [LAVA] water and LAVA fat, 120-second–delay T1-weighted LAVA water, and single-shot fast spin-echo T2 weighted) and clinical data. The model had a patient-level and voxel-level correlation of 0.50 ± 0.05 and 0.34 ± 0.03, respectively. By using a stiffness threshold of 3.54 kPa to make a binary classification into no fibrosis or mild fibrosis (F0–F1) versus clinically significant fibrosis (F2–F4), the model had sensitivity of 80% ± 4, specificity of 75% ± 5, accuracy of 78% ± 3, area under the receiver operating characteristic curve of 84 ± 0.04, and a Dice score of 0.74. CONCLUSION: The generation of virtual elastography images is feasible by using conventional MRI and clinical data with a machine learning algorithm. Keywords: MR Imaging, Abdomen/GI, Liver, Cirrhosis, Computer Applications/Virtual Imaging, Experimental Investigations, Feature Detection, Classification, Reconstruction Algorithms, Supervised Learning, Convolutional Neural Network (CNN) Supplemental material is available for this article. © RSNA, 2021

The need for liver transplants is increasing because the prevalence of liver diseases and the indications for transplants are growing. In response to the shortage of grafts from deceased donors, more transplants are being performed worldwide with grafts from living donors. Radiologic evaluation is an integral component in the assessment of donor candidates to ensure their eligibility and to choose the most appropriate surgical approach. MRI is the preferred modality for evaluation of the liver parenchyma and biliary tree. In most centers, a combination of MRI and CT is used to take advantage of the higher spatial resolution of CT for evaluation of arteries. However, MRI-only assessment is feasible. In addition to assessment of the liver parenchyma for abnormalities such as steatosis, a detailed evaluation of the hepatic vascular and biliary system for pertinent anatomic variants is crucial, because these variants can affect surgical techniques and outcomes in both recipients and donors. In this pictorial article, after a brief review of the most common surgical techniques and postsurgical liver anatomy, the biliary and vascular anatomy are discussed, with specific attention paid to the variants that are pertinent to this surgical procedure. The roles of liver segmentation and volumetric assessment and current imaging techniques and protocols are also discussed.

Purpose To compare the diagnostic performance of morphologic criteria for detection of cirrhosis in patients with alcoholic liver disease (ALD), hepatitis C (HCV), and non-alcoholic steatohepatitis (NASH). Methods One hundred patients (53 male) with different etiologies of chronic liver disease (NASH,n = 41; HCV,n = 39; and ALD,n = 20) and with different degrees of fibrosis on histopathologic examination (74 with cirrhosis) were retrospectively evaluated. Four readers (R1: fellowship-trained abdominal radiologist, R2: community attending radiologist, R3: senior radiology resident/research fellow, R4: junior radiology resident) analyzed the contrast-enhanced CTs for presence of commonly accepted morphologic changes of cirrhosis and portal hypertension. Each reader assigned an overall score (using a 5-point scale) for possibility of cirrhosis based on liver morphology and features of portal hypertension. Diagnostic performance, sensitivity, and specificity for the diagnosis of cirrhosis were calculated and compared between different etiologies of chronic liver disease. Results Performance of readers was affected by their level of training. Less experienced readers had overall lower sensitivity for diagnosis of cirrhosis in NASH group (R3: 81.5%, R4: 63.0% compared to 96.3% for both R1 and R2). Sensitivities for detection of NASH cirrhosis significantly decreased for less experienced readers in the absence of ascites (R3: 75.0%, R4: 62.0%) or other features of portal hypertension (R3: 50.0%; R4: 0%). The specificity was consistently high among different etiologies and for all readers (85.7-100%). Inter-reader agreement for morphologic features ranged widely from fair to almost perfect (k: 0.23-0.85). Conclusion Cirrhotic changes in NASH are subtler and can be underestimated by less experienced readers.

Liver transplant is indicated with curative intent for patients with early-stage hepatocellular carcinoma (HCC). The radiologic T category is used to determine candidacy and priority of patients on the waiting list. After transplant, the explant liver pathologic TNM stage is used as a predictor of postoperative outcomes and overall prognosis. Although the comparison of radiologic and pathologic T categories for concordance is often considered to be straightforward, the staging conventions significantly differ. Not accounting for these differences is in part the reason for the high rates of radiologic-pathologic discordance reported in the literature, with inconsistent terminology being an additional source of confusion when evaluating concordance. These factors may affect the understanding of important radiopathologic phenotypes of disease and the adequate investigation of their prognostic capabilities. The aims of this article are to provide an overview of the pathologic and radiologic TNM staging systems for HCC while describing staging procedures, emphasize the differences between these staging systems to highlight the limitations of radiologic-pathologic stage correlation, present a review of the literature on the prognostic value of individual features used for HCC staging; and signal significant aspects of preoperative risk stratification that could be improved to positively impact posttransplant outcomes.

SUMMARYOvereating and a sedentary life style are major causes of obesity and related metabolic disorders. Identification of the neurobiological processes that regulate energy balance will facilitate development of interventions for these disorders. Here we show that the Neurotensin-expressing neurons in the mouse IPAC (IPACNts), a nucleus of the central extended amygdala, bidirectionally coordinate hedonic feeding and physical activity, thereby regulating energy balance, metabolic processes and bodyweight. IPACNts are preferentially activated by consumption of highly palatable food or exposure to its taste and smell. Activating IPACNts promotes food intake in a palatability-dependent manner and decreases locomotion. Conversely, inhibiting IPACNts selectively reduces palatable food intake and dramatically enhances physical activity and energy expenditure, and in parallel stimulates physiological responses that oppose diet-induced obesity and metabolic dysfunctions. Thus, a single neuronal population, Neurotensin-expressing neurons in the IPAC, acts to control obesogenic and leptogenic processes by synergistically coordinating energy intake and expenditure with metabolism.

Cancer progression occurs in concomitance with a profound remodeling of the cellular microenvironment. Far from being a mere passive event, the re-orchestration of interactions between the various cell types surrounding tumors highly contributes to the progression of the latter. Tumors notably recruit and stimulate the sprouting of new blood vessels through a process called neo-angiogenesis. Beyond helping the tumor cope with an increased metabolic demand associated with rapid growth, this also controls the metastatic dissemination of cancer cells and the infiltration of immune cells in the tumor microenvironment. To decipher this critical interplay for the clinical progression of tumors, the research community has developed several valuable models in the last decades. This review offers an overview of the various instrumental solutions currently available, including microfluidic chips, co-culture models, and the recent rise of organoids. We highlight the advantages of each technique and the specific questions they can address to better understand the tumor immuno-angiogenic ecosystem. Finally, we discuss this development field’s fundamental and applied perspectives.

International audience; Control of cell death/survival balance is an important feature to maintain tissue homeostasis. Dependence receptors are able to induce either survival or cell death in presence or absence of their ligand, respectively. However, their precise mechanism of action and their physiological importance are still elusive for most of them including the MET receptor. We evidence that pro-apoptotic fragment generated by caspase cleavage of MET localizes to the mitochondria-associated membrane region. This fragment triggers a calcium transfer from endoplasmic reticulum to mitochondria, which is instrumental for the apoptotic action of the receptor. Knock-in mice bearing a mutation of MET caspase cleavage site highlighted that p40MET production is important for FAS-driven hepatocyte apoptosis, and demonstrate that MET acts as a dependence receptor in vivo. Our data shed light on new signaling mechanisms for dependence receptors' control of cell survival/death balance, which may offer new clues for the pathophysiology of epithelial structures.

Hepatocellular carcinoma (HCC) is the most common liver malignancy associated with chronic liver disease. Nonhepatocellular malignancies may also arise in the setting of chronic liver disease. The imaging diagnosis of non-HCC malignancies may be challenging. Non-HCC malignancies in patients with chronic liver disease most commonly include intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma, and less commonly hepatic lymphomas and metastases. On MR imaging, non-HCC malignancies often demonstrate a targetoid appearance, manifesting as rim arterial phase hyperenhancement, peripheral washout, central delayed enhancement, and peripheral restricted diffusion. When applying the Liver Imaging Reporting and Data System algorithm, observations with targetoid appearance are categorized as LR-M.

Vascular invasion by hepatocellular carcinoma (HCC), also known as tumor in vein (TIV), indicates highly invasive tumor behavior and is also associated with poor outcome. Because a diagnosis of TIV precludes liver transplantation, knowledge of the imaging findings to differentiate between TIV and bland thrombus is key for proper patient management. Prior versions of liver imaging reporting and data system (LI-RADS) included presence of TIV as part of LR-5 criteria. However, even if HCC is the most common liver malignancy associated with TIV, other tumors can have vascular invasion and may occur in cirrhotic patients. For these reasons, in LI-RADS v2017 LR-TIV has been introduced as a new different diagnostic category. The aim of this article is to discuss the diagnostic criteria of LR-TIV according to LI-RADS v2018 and analyze potential pitfalls encountered on daily clinical practice. Indeterminate cases and how to manage them will also be discussed.

OBJECTIVE: To characterize the use of multiparametric magnetic resonance imaging (mpMRI) in male Medicare beneficiaries electing active surveillance for prostate cancer. Multi-parametric resonance imaging (mpMRI) has emerged as a tool that may improve risk-stratification and decrease repeated biopsies in men electing active surveillance. However, the extent to which mpMRI has been implemented in active surveillance has not been established. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) registry data linked to Medicare claims data, we identified men with localized prostate cancer diagnosed between 2008–2013 and managed with active surveillance. We classified men into two treatment groups: active surveillance without mpMRI and active surveillance with mpMRI. We then fit a multivariable logistic regression models to examine changing mpMRI utilization over time, and factors associated with the receipt of mpMRI. RESULTS: We identified 9,467 men on active surveillance. Of these, 8,178 (86%) did not receive mpMRI and 1,289 (14%) received mpMRI. The likelihood of receiving mpMRI over the entire study period increased by 3.7% (p=0.004). On multivariable logistic regression, patients who were younger, white, had lower comorbidity burden, lived in the northeast and west, had higher incomes and lived in more urban areas had greater odds of receiving mpMRI (all p

The Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system for standardizing the terminology, technique, interpretation, reporting, and data collection of liver imaging, created specifically for patients at risk for hepatocellular carcinoma. Over the past years, LI-RADS has been progressively implemented into clinical practice, but pitfalls remain related to user error and inherent limitations of the system. User pitfalls include the inappropriate application of LI-RADS to a low-risk patient population, incorrect measurement techniques, inaccurate assumptions about LI-RADS requirements, and improper usage of LI-RADS terminology and categories. System pitfalls include areas of discordance with the Organ Procurement and Transplantation Network (OPTN) as well as pitfalls related to rare ancillary features. This article reviews common user pitfalls in applying LI-RADS v2018 and how to avoid preventable errors and also highlights deficiencies of the current version of LI-RADS and how it might be improved in the future. Level of Evidence:3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2019;50:1673-1686.

PurposeTo investigate the performance of MR-based texture analysis (TA) for the assessment of hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).MethodsFifty-four adult patients (33 females, 21 males, mean age 49.813.5years) with biopsy-proven NAFLD were enrolled and underwent MR imaging on a 1.5T system. TA parameters were extracted on axial noncontrast 3D-GRE T1W images (slice thickness=4.6mm) using a commercially available research software (TexRAD). Receiver operating curves (ROC), areas under the ROC (AUROC) and 95% confidence intervals (CI) were calculated to assess the accuracy of each TA parameter for the diagnosis of significant (F2) and advanced fibrosis (F3). The correlation between TA and histopathological features of nonalcoholic steatohepatitis (NASH) was tested calculating the Spearman's rank correlation coefficient ().ResultsThirty-seven (68%) subjects had significant fibrosis and 20 (37%) had advanced fibrosis. The TA parameters with the best performance were standard deviation (SD) and entropy, respectively, with AUROC 0.755 (95% CI 0.619-0.862, p0.0002) and 0.769 (95% CI 0.634-0.873, p

Among pediatric brain tumors, Diffuse Intrinsic Pontine Gliomas (DIPGs) display a particularly dismal prognosis, highlighted by their median survival lower than one year. Indeed, DIPGs’ location and infiltrative properties preclude their surgical resection. Moreover, DIPGs poorly respond to chemotherapeutic agents. In this context, the only treatment for these tumors remains palliative radiotherapy, systematically followed by tumor progression. In addition to their resistance to therapies, DIPGs are characterized by recurrent histone H3 mutations. The H3.3K27M mutation is the most frequent and results from a heterozygous single nucleotide variant in the H3F3A gene, inducing the lysine 27 substitution by a methionine. Although H3.3K27M’s driver role in DIPGs tumorigenesis is now established, its role in their chemo- and radioresistance remains unclear. Aiming to decipher the potential role of this mutation in pediatric gliomas’ resistance to therapies, we established isogenic cellular models of H3.3K27M induction and reversion.We first induced H3.3K27M mutation in three initially non-mutated supratentorial pediatric glioma cell lines. Thus, we generated models that stably expressed the dominant-negative H3.3K27M or the wild type H3.3 as controls. Complementarily, to study H3.3K27M roles in a DIPG cell context, we also developed H3.3K27M reversion models in two initially mutated DIPG cell lines by applying a gene-editing strategy based on the combinatorial use of the CRISPR/Cas9 technology and an insert.We showed that H3.3K27M induction in Res259 and KNS42 cells conferred a radioresistant phenotype to a fractionated radiotherapy schedule. Besides, we performed a screening of 80 anti-cancer drugs, which revealed a differential impact of the mutation on the drug sensitivity profiles of our three H3.3K27M-induced cell lines. These results indicate that H3.3K27M can control pediatric glioma cells’ resistance to therapies, but in a heterogeneous way depending on the cellular context. Along this line, we are currently characterizing the chemo- and radiotherapy response of our new DIPG H3.3K27M-reversed models. Altogether, our first results support a role for H3.3K27M in pediatric gliomas resistance to treatments, and our complementary models pave the way for identifying new H3.3K27M-dependent mechanisms and promising targets to sensitize DIPGs to therapies. Citation Format: Andria Rakotomalala, Paul Lewandowski, Quentin Bailleul, Clara Savary, Mélanie Arcicasa, Christine Bal, Maud Hamadou, Paul Huchedé, Audrey Restouin, Remy Castellano, Yves Collette, Audrey Vincent, Pierre-Olivier Angrand, Eric Adriaenssens, Xuefen Le Bourhis, Pierre Leblond, Marie Castets, Eddy Pasquier, Alessandro Furlan, Samuel Meignan. Engineering new cellular models to decipher H3.3K27M mutation role in DIPGs' resistance to therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1671.

Schwann cell precursors (SCPs) are multipotent embryonic progenitors covering all developing peripheral nerves. These nerves grow and navigate with unprecedented precision, delivering SCP progenitors to almost all locations in the embryonic body. Within specific developing tissues, SCPs detach from nerves and generate neuroendocrine cells, autonomic neurons, mature Schwann cells, melanocytes and other cell types. These properties of SCPs evoke resemblances between them and their parental population, namely, neural crest cells. Neural crest cells are incredibly multipotent migratory cells that revolutionized the course of evolution in the lineage of early chordate animals. Given this similarity and recent data, it is possible to hypothesize that proto-neural crest cells are similar to SCPs spreading along the nerves. Here, we review the multipotency of SCPs, the signals that govern them, their potential therapeutic value, SCP's embryonic origin and their evolutionary connections. We dedicate this article to the memory of Wilhelm His, the father of the microtome and "Zwischenstrang", currently known as the neural crest.

This study aimed to investigate whether magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) can be a viable noninvasive alternative to liver biopsy for the quantification of living liver donor steatosis. Hepatic steatosis for 143 donors was graded by MRI-PDFF. Study endpoints included liver volume regeneration in donors, recipient outcomes including length of hospital stay, deaths, primary non-function (PNF), early allograft dysfunction (EAD), and small for size syndrome (SFSS). Correlation between MRI-PDFF determined donor steatosis and endpoints were analyzed. Donors had lower steatosis grade than non-donors. Donor remnant liver regenerated to an average of 82% of pre-donation volume by 101 ± 24 days with no complications. There was no correlation between percent liver regeneration and steatosis severity. Among recipients, 4 underwent redo-transplantation and 6 died, with no association with degree of steatosis. 52 recipients (36%) fulfilled criteria for EAD (driven by INR), with no difference in hepatic steatosis between groups. MRI-PDFF reliably predicted donor outcomes. Living donors with no or mild steatosis based on MRI-PDFF (ie