Faculty Bibliography

BACKGROUND:Hypoxia-inducible factor 1α (HIF-1α) is a gene that regulates tumor survival, neovascularization and invasion. Overexpression of HIF-1α correlates with poor prognosis in hepatocellular carcinoma (HCC). RO7070179 is a HIF-1α inhibitor that decreases HIF-1α mRNA and its downstream targets, it could be a potential treatment in HCC. AIM/OBJECTIVE:To evaluate safety and preliminary activity of RO7070179 in patients with previously treated HCC, with focus on a patient with prolonged response to RO7070179. METHODS:In the preclinical study of RO7070179 in a HCC xenograft model, the mice were separated into 4 groups with each group received doses of 0, 3, 10 and 30 mg/kg for total 10 doses. HCC patients who failed at least one line of systemic treatment, received RO7070179 as a weekly infusion, each cycle is 6 wk. We evaluated the safety and HIF-1α mRNA levels of RO7070179. RESULTS:Preclinical evaluation of RO7070179 in orthotopic HCC xenograft model showed no significant differences in HCC tumor weight between the 3 and 10 mg/kg groups. However, dose of 10 mg/kg of RO7070179, has shown 76% reduction of the amount of HIF-1α mRNA in HCC tissue. In the phase 1b study of RO7070179 in previously treated HCC patients, 8 out of 9 were evaluable: 1 achieved PR and 1 SD. The patient with PR responded after 2 cycles treatments, which has been maintained for 12 cycles. This patient also showed reduction in perfusion of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) after 1 cycle of treatment. After 1 cycle of treatment, both patients with PR and SD showed decrease in HIF-1α mRNA at the root of biopsies (each biopsy was divided into 2 specimens, the tip and the root). CONCLUSION/CONCLUSIONS:RO7070179 can reduce HIF-1α mRNA level in HCC patients with SD or PR. It is well tolerated at 10 mg/kg, with transaminitis as the dose of increased toxicity. This study indicates that RO7070179 might benefit HCC patients, and an early signal for clinical benefit can potentially be predicted through changes in either mRNA level or DCE-MRI within 1 cycle of therapy.

OBJECTIVE:Beginning a new job after radiology training is exciting but can also be nerve-racking. The key challenge remains making the strange familiar and assimilating with the new practice as soon as possible. This process is complicated and may require learning new policies, getting to know new colleagues, adapting to new surroundings, and learning new skills. CONCLUSION/CONCLUSIONS:This article provides strategies to navigate professionally and adapt to a new environment.

This article presents methods to improve MR imaging approach of disorders of the renal sinus which are relatively uncommon and can be technically challenging. Multi-planar Single-shot T2-weighted (T2W) Fast Spin-Echo sequences are recommended to optimally assess anatomic relations of disease. Multi-planar 3D-T1W Gradient Recalled Echo imaging before and after Gadolinium administration depicts the presence and type of enhancement and relation to arterial, venous, and collecting system structures. To improve urographic phase MRI, concentrated Gadolinium in the collecting systems should be diluted. Diffusion-Weighted Imaging (DWI) should be performed before Gadolinium administration to minimize T2* effects. Renal sinus cysts are common but can occasionally be confused for dilated collecting system or calyceal diverticula, with the latter communicating with the collecting system and filling on urographic phase imaging. Vascular lesions (e.g., aneurysm, fistulas) may mimic cystic (or solid) lesions on non-enhanced MRI but can be suspected by noting similar signal intensity to the blood pool and diagnosis can be confirmed with MR angiogram/venogram. Multilocular cystic nephroma commonly extends to the renal sinus, however, to date are indistinguishable from cystic renal cell carcinoma (RCC). Solid hilar tumors are most commonly RCC and urothelial cell carcinoma (UCC). Hilar RCC are heterogeneous, hypervascular with epicenter in the renal cortex compared to UCC which are centered in the collecting system, homogeneously hypovascular, and show profound restricted diffusion. Diagnosis of renal sinus invasion in RCC is critically important as it is the most common imaging cause of pre-operative under-staging of disease. Fat is a normal component of the renal sinus; however, amount of sinus fat correlates with cardiovascular disease and is also seen in lipomatosis. Fat-containing hilar lesions include lipomas, angiomyolipomas, and less commonly other tumors which engulf sinus fat. Mesenchymal hilar tumors are rare. MR imaging diagnosis is generally not possible, although anatomic relations should be described to guide diagnosis by percutaneous biopsy or surgery.

The Liver Imaging and Reporting Data System (LI-RADS) is a comprehensive system for standardizing the terminology, technique, interpretation, reporting, and data collection of liver imaging with the overarching goal of improving communication, clinical care, education, and research relating to patients at risk for or diagnosed with hepatocellular carcinoma (HCC). In 2018, the American Association for the Study of Liver Diseases (AASLD) integrated LI-RADS into its clinical practice guidance for the imaging-based diagnosis of HCC. The harmonization between the AASLD and LI-RADS diagnostic imaging criteria required minor modifications to the recently released LI-RADS v2017 guidelines, necessitating a LI-RADS v2018 update. This article provides an overview of the key changes included in LI-RADS v2018 as well as a look at the LI-RADS v2018 diagnostic algorithm and criteria, technical recommendations, and management suggestions. Substantive changes in LI-RADS v2018 are the removal of the requirement for visibility on antecedent surveillance ultrasound for LI-RADS 5 (LR-5) categorization of 10-19 mm observations with nonrim arterial phase hyper-enhancement and nonperipheral "washout", and adoption of the Organ Procurement and Transplantation Network definition of threshold growth (≥ 50% size increase of a mass in ≤ 6 months). Nomenclatural changes in LI-RADS v2018 are the removal of -us and -g as LR-5 qualifiers.

PURPOSE: To develop and evaluate a novel dynamic contrast-enhanced imaging technique called RACER-GRASP (Respiratory-weighted, Aortic Contrast Enhancement-guided and coil-unstReaking Golden-angle RAdial Sparse Parallel) MRI that extends GRASP to include automatic contrast bolus timing, respiratory motion compensation, and coil-weighted unstreaking for improved imaging performance in liver MRI. METHODS: In RACER-GRASP, aortic contrast enhancement (ACE) guided k-space sorting and respiratory-weighted sparse reconstruction are performed using aortic contrast enhancement and respiratory motion signals extracted directly from the acquired data. Coil unstreaking aims to weight multicoil k-space according to streaking artifact level calculated for each individual coil during image reconstruction, so that coil elements containing a high level of streaking artifacts contribute less to the final results. Self-calibrating GRAPPA operator gridding was applied as a pre-reconstruction step to reduce computational burden in the subsequent iterative reconstruction. The RACER-GRASP technique was compared with standard GRASP reconstruction in a group of healthy volunteers and patients referred for clinical liver MR examination. RESULTS: Compared with standard GRASP, RACER-GRASP significantly improved overall image quality (average score: 3.25 versus 3.85) and hepatic vessel sharpness/clarity (average score: 3.58 versus 4.0), and reduced residual streaking artifact level (average score: 3.23 versus 3.94) in different contrast phases. RACER-GRASP also enabled automatic timing of the arterial phases. CONCLUSIONS: The aortic contrast enhancement-guided sorting, respiratory motion suppression and coil unstreaking introduced by RACER-GRASP improve upon the imaging performance of standard GRASP for free-breathing dynamic contrast-enhanced MRI of the liver. Magn Reson Med, 2017. (c) 2017 International Society for Magnetic Resonance in Medicine.

BACKGROUND:Portal vein thrombosis (PVT) develops in cirrhotic patients because of stagnation of blood flow. Transjugular intrahepatic portosystemic shunt (TIPS) creates a low-resistance conduit that restores portal venous patency and blood flow. AIM/OBJECTIVE:The effect of PVT on transplant-free survival in cirrhotic patients undergoing TIPS creation was evaluated. PATIENTS AND METHODS/METHODS:A multicenter, retrospective cohort study of patients who underwent TIPS creation for cirrhotic portal hypertension was carried out. A Cox model with propensity score adjustment was developed to evaluate the effect of PVT on 90-day and 3-year transplant-free survival. A subgroup analysis examining mortality of those with superior and distal PVT was also carried out. RESULTS:A total of 252 consecutive TIPS creations were assessed, including 65 in patients with PVT. Survival of patients with high Model for End-stage Liver Disease scores (≥18) and PVT was not statistically different compared with patients with low Model for End-stage Liver Disease scores (<18) and no PVT at 90 days (P=0.46) and 3 years (P=0.42). Those with inferior PVT had improved 90-day and 3-year survival both compared with patients with a superior PVT and those without a PVT (P<0.01, all cases). CONCLUSION/CONCLUSIONS:The presence of PVT does not impair the prognosis of patients following TIPS creation, particularly in patients with distal portal occlusion.

PURPOSE: To develop and test a deep learning approach named Convolutional Neural Network (CNN) for automated screening of T2 -weighted (T2 WI) liver acquisitions for nondiagnostic images, and compare this automated approach to evaluation by two radiologists. MATERIALS AND METHODS: We evaluated 522 liver magnetic resonance imaging (MRI) exams performed at 1.5T and 3T at our institution between November 2014 and May 2016 for CNN training and validation. The CNN consisted of an input layer, convolutional layer, fully connected layer, and output layer. 351 T2 WI were anonymized for training. Each case was annotated with a label of being diagnostic or nondiagnostic for detecting lesions and assessing liver morphology. Another independently collected 171 cases were sequestered for a blind test. These 171 T2 WI were assessed independently by two radiologists and annotated as being diagnostic or nondiagnostic. These 171 T2 WI were presented to the CNN algorithm and image quality (IQ) output of the algorithm was compared to that of two radiologists. RESULTS: There was concordance in IQ label between Reader 1 and CNN in 79% of cases and between Reader 2 and CNN in 73%. The sensitivity and the specificity of the CNN algorithm in identifying nondiagnostic IQ was 67% and 81% with respect to Reader 1 and 47% and 80% with respect to Reader 2. The negative predictive value of the algorithm for identifying nondiagnostic IQ was 94% and 86% (relative to Readers 1 and 2). CONCLUSION: We demonstrate a CNN algorithm that yields a high negative predictive value when screening for nondiagnostic T2 WI of the liver. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.

PURPOSE: To evaluate the impact of questionnaires completed by patients at the time of abdominopelvic CT performed for abdominal pain on the completeness of clinical information and the identification of potential causes of pain, compared with order requisitions alone. METHODS: 100 outpatient CT examinations performed for the evaluation of abdominal pain were retrospectively reviewed. The specificity of the location of pain was compared between the order requisition and patient questionnaire. An abdominal imaging fellow (Reader 1) and abdominal radiologist (Reader 2) reviewed the examinations independently in two sessions 6 weeks apart (one with only the order requisition and one also with the questionnaire). Readers recorded identified causes of pain and rated their confidence in interpretation (1-5 scale; least to greatest confidence). RESULTS: In 30% of patients, the questionnaire provided a more specific location for pain. Among these, the pain was localized to a specific quadrant in 40%. With having access to the questionnaire, both readers identified additional causes for pain not identified in session 1 (Reader 1, 8.6% [7/81]; Reader 2 5.3% [4/75]). Additional identified causes of pain included diverticulitis, cystitis, peritoneal implants, epiploic appendagitis, osseous metastatic disease, umbilical hernia, gastritis, and SMA syndrome. Confidence in interpretation was significantly greater using the questionnaire for both readers (Reader 1: 4.8 +/- 0.6 vs. 4.0 +/- 0.5; Reader 2: 4.9 +/- 0.3 vs. 4.7 +/- 0.5, p < 0.001). CONCLUSION: Patient questionnaires provide additional relevant clinical history, increased diagnostic yield, and improve radiologists' confidence. Radiology practices are encouraged to implement questionnaires and make these readily available to radiologists at the time of interpretation.