Faculty Bibliography

PURPOSE/OBJECTIVE:To compare liver stiffness measurements obtained from MR elastography with liver T1 relaxation times obtained from T1 mapping and T2 relaxation times obtained from T2 mapping for detection and staging of liver fibrosis. MATERIALS AND METHODS/METHODS:223 patients with known or suspected liver disease underwent MRI of the liver with T1 mapping (Look-Locker sequence) and 2D SE-EPI MR elastography (MRE) sequences. 139 of these patients also underwent T2 mapping with radial T2 TSE sequence. Two readers (R1 & R2) measured liver stiffness, T1 relaxation times and T2 relaxation times. T1 and T2 times were correlated with stiffness measurements. ROC analysis was used to compare the performance of both techniques in discriminating fibrosis stage in 23 patients who underwent liver biopsy. RESULTS:For each reader there was significant moderate positive correlation between liver MRE and liver T1 mapping (r = 0.49 and 0.36). There was significant moderate positive correlation between liver T2 mapping and each of MRE and T1 mapping for one of the readers (r = 0.40 and 0.27). AUC for differentiating early (F0-F2) from advanced (F3-F4) fibrosis in biopsied patients was 0.975 (R1) and 0.925 (R2) for MRE, 0.671 (R1) and 0.642 (R2) for T1 mapping and 0.671 (R1) and 0.743 (R2) for T2 mapping. Inter-reader agreement was good for MRE (ICC = 0.84) substantial for T1 mapping (0.94) and T2 mapping (0.96). CONCLUSIONS:Liver T1 and T2 mapping showed moderate positive correlation with MR elastography. Accuracy of MRE is however superior to T1 and T2 mapping in the subset of patients who underwent liver biopsy. Accuracy of combination of MRE and T1 mapping/T2 mapping was not superior to MRE alone.

PURPOSE/OBJECTIVE:To investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS/METHODS:This single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A-B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses. RESULTS:The median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6-11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1-3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9-23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6-26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2-7.2), and progression-free survival was 5.7 months (95% CI, 4.3-7.1). CONCLUSIONS:Radioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.

Magnetic resonance imaging of the upper tract (pyelocalyces and ureters) or MR Urography (MRU) is technically possible and when performed correctly offers similar visualization of the upper tracts and for detection of non-calculous diseases of the collecting system similar specificity but with lower sensitivity compared to CTU. MRU provides the ability to simultaneously image the kidneys and urinary bladder with improved soft tissue resolution, better tissue characterization and when combined with assessment of the upper tract, a comprehensive examination of the urinary system. MRU requires meticulous attention to technical details and is a longer more demanding examination compared to CTU. Advances in MR imaging techniques including: parallel imaging, free-breathing motion compensation techniques and compressed sensing can dramatically shorten examination times and improve image quality and patient tolerance for the exam. This review article discusses updates in the MRU technique, summarizes clinical indications and opportunities for MRU in clinical practice and reviews advantages and disadvantages of MRU compared to CTU.

BACKGROUND:Evaluation of prostate MRI relies on diffusion-weighted imaging (DWI), commonly distorted by susceptibility artifacts, thereby creating a need for approaches to correct such distortion. PURPOSE/OBJECTIVE:To compare geometric distortion on prostate MRI between standard DWI and a geometric distortion correction method for DWI described as static distortion correction DWI (SDC DWI). STUDY TYPE/METHODS:Retrospective case study. POPULATION/METHODS:Thirty patients (ages 31-81 years) undergoing prostate MRI. SEQUENCE/UNASSIGNED:-field map to estimate geometric distortions. ASSESSMENT/RESULTS:WI) as an anatomic standard. Pixel shifts and apparent diffusion coefficient (ADC) values were compared between prostate contours applied to the SDC DWI and standard DWI sequences. Detailed characterization of the impact of SDC DWI was performed in three representative patients. STATISTICAL TESTS/UNASSIGNED:One-way analysis of variance (ANOVA) test, Spearman correlation test, and Bland-Altman plots were calculated. RESULTS:= 0.21). DATA CONCLUSION/UNASSIGNED:SDC DWI appears to correct for susceptibility-related pixel shifts in the prostate compared with standard DWI, which may have value for assessing prostate lesions obscured by geometric warping. Level of Evidence 4 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2019.

PURPOSE/OBJECTIVE:To compare qualitative results obtained from computer-aided dual-ratio analysis on T1-weighted two-point Dixon, with T2*-corrected multi-echo Dixon and T2-corrected multi-echo single-voxel MR spectroscopy sequence (MRS) for evaluation of liver fat and iron at 3T. METHODS AND MATERIALS/METHODS:This retrospective, HIPAA-compliant, IRB-approved study included 479 patients with known or suspected liver disease. Two-point Dixon, multi-echo Dixon, and MR spectroscopy sequences were performed for each patient at 3T. A receiver-operating characteristic analysis was performed to compare the diagnostic performance in 80 patients using biopsy as the standard. Sensitivity, specificity, PPV, and NPV of qualitative two-point Dixon results, multi-echo Dixon (PDFF and R2*), and MRS (fat fraction and R2 water) for detection of hepatic steatosis and siderosis were assessed. RESULTS:, respectively. CONCLUSION/CONCLUSIONS:The computer-aided dual-ratio discrimination with two-point Dixon is a useful qualitative screening tool with high negative predictive value for hepatic steatosis and iron overload. Multi-echo Dixon and MRS have similar accuracy for detection of hepatic steatosis and iron overload at 3 Tesla.

PURPOSE/OBJECTIVE:To determine the utility of an automated radiology-pathology feedback tool. METHODS:We previously developed a tool that automatically provides radiologists with pathology results related to imaging examinations they interpreted. The tool also allows radiologists to mark the results as concordant or discordant. Five abdominal radiologists prospectively scored their own discordant results related to their previously interpreted abdominal ultrasound, CT, and MR interpretations between August 2017 and June 2018. Radiologists recorded whether they would have followed up on the case if there was no automated alert, reason for the discordance, whether the result required further action, prompted imaging rereview, influenced future interpretations, enhanced teaching files, or inspired a research idea. RESULTS:There were 234 total discordances (range 30-66 per radiologist), and 70.5% (165 of 234) of discordances would not have been manually followed up in the absence of the automated tool. Reasons for discordances included missed findings (10.7%; 25 of 234), misinterpreted findings (29.1%; 68 of 234), possible biopsy sampling error (13.3%; 31 of 234), and limitations of imaging techniques (32.1%; 75/234). In addition, 4.7% (11 of 234) required further radiologist action, including report addenda or discussion with referrer or pathologist, and 93.2% (218 of 234) prompted radiologists to rereview the images. Radiologists reported that they learned from 88% (206 of 234) of discordances, 38.6% (90 of 233) of discordances probably or definitely influenced future interpretations, 55.6% (130 of 234) of discordances prompted the radiologist to add the case to his or her teaching files, and 13.7% (32 of 233) inspired a research idea. CONCLUSION/CONCLUSIONS:Automated pathology feedback provides a valuable opportunity for radiologists across experience levels to learn, increase their skill, and improve patient care.

PURPOSE/OBJECTIVE:To assess subspecialty mix and case volumes of general and abdominal subspecialty radiologists interpreting abdominal MRI. METHODS:The 2016 CMS Physician/Supplier Procedure Summary Master File was used to obtain billed counts of radiologist-interpreted abdominal fluoroscopy, US, CT, and MRI examinations. The CMS Physician and Other Supplier Public Use File was used to assess the subspecialty mix and case volume of the radiologists interpreting those examinations. RESULTS:The fraction of all abdominal imaging examinations interpreted by generalists and abdominal subspecialty radiologists was 70.7% and 16.5% for fluoroscopy; 68.7% and 21.0% for US; 71.4% and 19.2% for CT; and 41.9% and 52.5% for MRI. In 2016, the fraction of general and abdominal radiologists interpreting > 50 fluoroscopy examinations on Medicare fee-for-service beneficiaries was 15.1% and 16.2%. For > 50 US examinations, the fraction was 61.5% and 60.5%; for > 50 CT examinations, 91.2% and 79.6%; and for > 50 MRI examinations, 4.0% and 28.5%. The fraction of abdominal imaging examinations interpreted overall by low-volume providers (those interpreting ≤ 50 examinations in 2016) was 59.5% for fluoroscopy, 17.5% for US, 6.3% for CT, and 50.6% for MRI. CONCLUSION/CONCLUSIONS:Nationally, most abdominal fluoroscopy, US, and CT examinations are interpreted by general radiologists, who have similar annual volumes of these examinations as abdominal subspecialty radiologists. In contrast, most abdominal MRI examinations are interpreted by abdominal subspecialty radiologists, who attain considerably higher volumes. These findings have implications for workforce planning and abdominal imaging fellowship design to ensure their graduates are optimally prepared to contribute to their future practices.

PURPOSE/OBJECTIVE:To compare 2D gradient-recalled echo (GRE) and 2D spin-echo (SE) echo-planar imaging (EPI) MR elastography (MRE) for measurement of hepatic stiffness in adult patients with known or suspected liver disease at 3 Tesla. MATERIALS AND METHODS/METHODS:Three hundred and eighty-seven consecutive patients underwent MRE of the liver at 3 Tesla with 2D-GRE and 2D-SE-EPI sequences. 'Mean liver stiffness (LS)' calculated by averaging 3 ROIs in the right lobe, 'Maximum LS' calculated by an ROI in the right lobe; and 'Freehand LS' calculated by an ROI in the entire liver were measured by two independent readers. Inter-observer and inter-class variability in stiffness measurements were assessed. Stiffness values were correlated with degree of liver fibrosis (METAVIR scores) in 97 patients who underwent biopsy. The diagnostic performance was compared by a receiver-operating characteristic analysis. RESULTS:indicating iron overload). There is high reproducibility for both GRE and SE-EPI variants (ICC = 0.84-0.94 for both GRE and SE-EPI MRE). The highest sensitivity, specificity, and accuracy of differentiating mild fibrosis (F0-F2) from advanced fibrosis (F3-F4) are 0.84 (GRE Freehand measurement), 0.92 (GRE Maximum stiffness measurement), and 0.88 (GRE Freehand measurement), respectively. CONCLUSIONS:High intra-class correlation and intra-reader correlation are seen on measured hepatic stiffness for both 2D-GRE and 2D-SE-EPI MRE. 2D-SE-EPI has lower failure rate. Diagnostic performance of both sequences is equivalent, with highest sensitivity for 2D-GRE Freehand stiffness measurement, and highest specificity 2D-GRE Maximum stiffness measurement.

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.