3D MR elastography-based stiffness as a marker for predicting tumor grade and subtype in cervical cancer.

BACKGROUND: Increasing evidence has indicated that high tissue stiffness (TS) may be a potential biomarker for evaluation of tumor aggressiveness. PURPOSE: To investigate the value of magnetic resonance elastography (MRE)-based quantitative parameters preoperatively predicting the tumor grade and subtype of cervical cancer (CC). STUDY TYPE: Retrospective. POPULATION: Twenty-five histopathology-proven CC patients and 7 healthy participants. FIELD STRENGTH/SEQUENCE: 3.0T, magnetic resonance imaging (MRI) (LAVA-flex) and MRE with a three-dimensional spin-echo echo-planar imaging. ASSESSMENT: The regions of interest (ROIs) were manually drawn by two observers in tumors to measure mean TS, storage modulus (G'), loss modulus (G″) and damping ratio (DR) values. Surgical specimens were evaluated for tumor grades and subtypes. STATISTICAL TESTS: Intraclass correlation coefficient (ICC) was expressed in terms of inter-observer agreements. t-test or Mann-Whitney nonparametric test was used to compare the complex modulus and apparent diffusion coefficient (ADC) values between different tumor groups. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the diagnostic performance. RESULTS: The TS of endocervical adenocarcinoma (ECA) group was significantly higher than that in squamous cell carcinoma (SCC) group (5.27 kPa vs. 3.44 kPa, P = 0.042). The TS also showed significant difference between poorly and well/moderately differentiated CC (5.21 kPa vs. 3.47 kPa, P = 0.038), CC patients and healthy participants (4.18 kPa vs. 1.99 kPa, P < 0.001). The cutoff value of TS to discriminate ECA from SCC was 4.10 kPa (AUC: 0.80), while it was 4.42 kPa to discriminate poorly from well/moderately differentiated CC (AUC: 0.83), and 2.25 kPa to distinguish normal cervix from CC (AUC: 0.88), respectively. There were no significant difference in G″, DR and ADC values between any subgroups except for comparison of healthy participants and CC patients (P = 0.001, P = 0.004, P < 0.001, respectively). DATA CONCLUSION: 3D MRE-assessed TS shows promise as a potential biomarker to preoperatively assess tumor grade and subtype of CC.

MR elastography as a biomarker for prediction of early and late recurrence in HBV-related hepatocellular carcinoma patients before hepatectomy.

PURPOSE: To investigate the diagnostic performance of preoperative MR elastography (MRE) in predicting early recurrence (ER) and late recurrence (LR) of HCC after hepatectomy. METHOD: In total, 180 patients (median age, 52 years; interquartile range, 41-50 years; 161 men) who underwent conventional MRI and MRE before hepatectomy between December 2014 and April 2020 were retrospectively recruited. A preoperative clinic-radiologic model and a combined postoperative clinic-pathologic and radiologic model were built using quantitatively MRE-derived stiffnesses, and image features to predict tumor ER and LR after hepatectomy. The Cox proportional hazards model and ROC analyses were used to identify the value of parameters to predict ER and LR. RESULTS: Seventy-three (40.5%) and 16 (8.9%) developed ER and LR after hepatectomy, respectively. For prediction of ER, the preoperative model integrated higher tumor stiffness (TS) (hazard ratio [HR],1.142; p < 0.001) with AFP ≥ 400 ng/mL (HR,1.761; p = 0.022), multifocal tumors (HR,3.229; p < 0.001) and lower ADC (HR,0.998; p = 0.017) variables; and the postoperative model incorporated higher TS, microvascular invasion, multifocal tumors, Child-Pugh class and ADC predictors. The two models provided comparable predictive performance (pre- 0.812 vs. post- 0.834, p = 0.283). Moreover, TS alone had a high sensitivity (90.4%) for predicting ER. Liver stiffness (LS) (HR, 1.757; p < 0.001) was the only independent predictor for LR in multivariate analysis in both the pre- and postoperative models with high specificity (90.0%), and its AUC with an optimal cut-off of 3.62 kPa was 0.860. CONCLUSIONS: Quantitative MRE-based stiffness is a useful biomarker for preoperative prediction of ER and LR of HCC.

Magnetic resonance elastography of the prostate in patients with lower urinary tract symptoms: feasibility of the modified driver at high multi-frequencies.

PURPOSE: To demonstrate the feasibility and diagnostic value of high-frequency magnetic resonance elastography (MRE) for evaluation of prostatic disease in patients with lower urinary tract symptoms (LUTS). METHODS: 41 patients who underwent preoperative prostate MRI and MRE with a modified driver were enrolled retrospectively from May 2016 to September 2021. All were included in the assessment of MRE image quality, using a qualitative visual inspection and a quantitative confidence map. 35 patients (prostate cancer (PCa), n = 13; non-PCa, n = 22) undergoing prostatectomy or biopsy were evaluated for the diagnostic performance of stiffness values. The confidence values and the stiffness values were analyzed by one-way analysis of variance (ANOVA) and independent samples T test, respectively. Area under the receiver operating characteristic (AUROC) analysis was performed. RESULTS: Through the qualitative analysis, all MRE acquisitions were successful at 60, 90, 120 and 150 Hz. The quantitative confidence values were significantly lower at 60 Hz (0.683 ± 0.055) and 90 Hz (0.762 ± 0.048) than that at 120 Hz (0.814 ± 0.049) and 150 Hz (0.840 ± 0.049), all P < 0.001. The stiffness of PCa was higher than non-PCa at 90 Hz (P = 0.008), 120 Hz (P < 0.001) and 150 Hz (P < 0.001). The AUCs were 0.773, 0.881 and 0.944, respectively. CONCLUSION: Prostate MRE using the modified driver is feasible at 60-150 Hz and image quality is better at higher frequencies. Prostate MRE may be useful and helpful to evaluate prostate diseases in patients with LUTS at higher frequencies; however, further study may be warranted with larger population in future.

Can modified LI-RADS increase the sensitivity of LI-RADS v2018 for the diagnosis of 10-19 mm hepatocellular carcinoma on gadoxetic acid-enhanced MRI?

PURPOSE: To evaluate whether the Liver Imaging Reporting and Data System (LI-RADS) v2018 LR-5 criteria can be modified to increase sensitivity without reducing specificity for diagnosing 10-19 mm hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (MRI). METHODS: A total of 133 high-risk consecutive patients with 174 small observations (10-19 mm) detected on gadoxetic acid-enhanced MRI were retrospectively studied. LI-RADS MRI major features (MFs) and ancillary features (AFs) were reviewed by two independent radiologists in consensus. Observations were categorized using LI-RADS v2018 MFs. Independently significant AFs were identified through logistic regression analysis. Upgraded LR-5 criteria were developed by combining independently significant AFs with MFs of LR-3 or LR-4 v2018. The sensitivity and specificity of the new diagnostic criteria were compared with those of LR-5 v2018 using McNemar's test. RESULTS: Three of the AFs favoring malignancy [mild-moderate T2 hyperintensity, transitional phase (TP) hypointensity and fat in mass] were independently significant features for diagnosing 10-19 mm HCC. The upgraded LR-5 criteria (mLI-RADS VII: LR-4 + mild-moderate T2 hyperintensity/TP hypointensity or LR-3 + fat in mass) yielded a significantly greater sensitivity than that of the LR-5 v2018 criteria (70.4% vs 55.1%; p < 0.001), whereas the specificity was not significantly different (94.7% vs 98.7%, p = 0.250). CONCLUSIONS: Independently significant AFs may be used to upgrade an observation from LR-3/LR-4 to LR-5, which can improve the sensitivity without impairing the specificity for diagnosing 10-19 mm HCC on gadoxetic acid-enhanced MRI.

Comparison of Gadobenate-Enhanced MRI and Gadoxetate-Enhanced MRI for Hepatocellular Carcinoma Detection Using LI-RADS Version 2018: A Prospective Intraindividual Randomized Study.

BACKGROUND. Gadobenate and gadoxetate show different degrees of intracellular accumulation within hepatocytes, potentially impacting these agents' relative performance for hepatocellular carcinoma (HCC) diagnosis. OBJECTIVE. The purpose of this article was to perform an intraindividual comparison of gadobenate-enhanced MRI and gadoxetate-enhanced MRI for detection of HCC and to assess the impact of inclusion of hepatobiliary phase images on HCC detection for both agents. METHODS. This prospective study enrolled 126 patients (112 men, 14 women; mean age, 52.3 years) at high risk for HCC who consented to undergo two 3-T liver MRI examinations (one using gadobenate [0.05 mmol/kg], one using gadoxetate [0.025 mmol/kg]) separated by 7-14 days. The order of the two contrast agents was randomized. All examinations included postcontrast dynamic and hepatobiliary phase images (120 minutes for gadobenate, 20 minutes for gadoxetate). Three radiologists independently reviewed the gadobenate and gadoxetate examinations in separate sessions and recorded the location of detected observations. Observations were classified using LI-RADS version 2018 and using a LI-RADS modification whereby hepatobiliary phase hypointensity may upgrade observations from category LR-4 to LR-5. Observations classified as LR-5 were considered positive interpretations for HCC. Diagnostic performance for histologically confirmed HCC (n = 96) was assessed. RESULTS. Across readers, sensitivity for HCC for gadobenate versus gadoxetate was 74.0-80.2% versus 54.2-67.7% using dynamic images alone and 82.1-87.4% versus 66.3-81.1% using dynamic and hepatobiliary phase images. For HCCs measuring 1.0-2.0 cm, sensitivity for gadobenate versus gadoxetate was 61.9% (all readers) versus 38.1-57.1% using dynamic images alone and 76.2-85.7% versus 52.4-61.9% using dynamic and hepatobiliary phase images. PPV for HCC ranged from 88.6% to 97.4% across readers, agents, and image sets. CONCLUSION. Sensitivity for HCC was higher for gadobenate than for gadoxetate, whether using dynamic images alone or dynamic and hepatobiliary phase images; the improved sensitivity using gadobenate was more pronounced for small HCCs. Whereas hepatobiliary phase images improved sensitivity for both agents, sensitivity of gadobenate using dynamic images alone compared favorably with that of gadoxetate using dynamic and hepatobiliary phase images. CLINICAL IMPACT. The findings support gadobenate as a preferred agent over gadoxetate when performing liver MRI in patients at high risk for HCC.

Tumor stiffness measured by 3D magnetic resonance elastography can help predict the aggressiveness of endometrial carcinoma: preliminary findings.

BACKGROUND: Preoperative evaluation of aggressiveness, including tumor histological subtype, grade of differentiation, Federation International of Gynecology and Obstetrics (FIGO) stage, and depth of myometrial invasion, is significant for treatment planning and prognosis in endometrial carcinoma (EC). The purpose of this study was to evaluate whether three-dimensional (3D) magnetic resonance elastography (MRE) can help predict the aggressiveness of EC. METHODS: From August 2015 to January 2019, 82 consecutive patients with suspected uterine tumors underwent pelvic MRI and MRE scans, and 15 patients with confirmed EC after surgical resection were enrolled. According to pathological results (tumor grade, histological subtype, FIGO stage, and myometrial invasiveness), the patients were divided into two subgroups. The independent-samples t-test or Mann-Whitney U test was used to compare the stiffness between different groups. The diagnostic performance was determined with receiver operating characteristic (ROC) curve analysis. RESULTS: The stiffness of EC with ≥ 50 % (n = 6) myometrial invasion was significantly higher than that with < 50 % (n = 9) myometrial invasion (3.68 ± 0.59 kPa vs. 2.61 ± 0.72 kPa, p = 0.009). Using a stiffness of 3.04 kPa as a cutoff value resulted in 100 % sensitivity and 77.8 % specificity for differentiating ≥ 50 % myometrial invasion from < 50 % myometrial invasion of EC. The stiffness of poorly differentiated EC (n = 8) was significantly higher than that of well/moderately differentiated EC (n = 7) (3.47 ± 0.64 kPa vs. 2.55 ± 0.82 kPa, p = 0.028). Using a stiffness of 3.04 kPa as a cutoff value resulted in 75 % sensitivity and 71.4 % specificity for differentiating poorly differentiated from well/moderately differentiated EC. The stiffness of FIGO stage II/III EC was significantly higher than that of FIGO stage I EC (3.69 ± 0.65 kPa vs. 2.72 ± 0.76 kPa, p = 0.030). Using a stiffness of 3.04 kPa as a cutoff value resulted in 100 % sensitivity and 70 % specificity for differentiating FIGO stage I EC from FIGO stage II/III EC. The tumor stiffness value in type II (n = 3) EC was higher than that in type I (n = 12) EC (3.67 ± 0.59 kPa vs. 2.88 ± 0.85 kPa), but the difference was not significant (p = 0.136). CONCLUSIONS: Tumor stiffness measured by 3D MRE may be potentially useful for predicting tumor grade, FIGO stage and myometrial invasion of EC and can aid in the preoperative risk stratification of EC.

Comparison of the diagnostic performance of 2D and 3D MR elastography in staging liver fibrosis.

OBJECTIVES: To compare the diagnostic performance and image quality of state-of-the-art 2D MR elastography (MRE) and 3D MRE in the basic application of liver fibrosis staging. METHODS: This retrospective study assessed data from 293 patients who underwent 2D and 3D MRE examinations. MRE image quality was assessed with a qualitative 2-point grading system by evaluating artifacts. Two experienced analysts independently measured mean liver stiffness values. The interobserver agreement of liver stiffness measurement was assessed by the intraclass correlation coefficient (ICC). The area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic performance of 2D and 3D MRE and blood-based markers for fibrosis staging using the pathology-proven liver fibrosis stage as the gold standard. RESULTS: The image quality provided by 3D MRE was graded as significantly higher than that obtained with the 2D MRE method (p < 0.01). Interobserver agreement in liver stiffness measurements was higher for 3D MRE (ICC: 3D 0.979 vs 2D 0.955). The AUC values for discriminating ≥ F1, ≥ F2, ≥ F3, and F4 fibrosis for 3D MRE (0.89, 0.92, 0.95, and 0.93) were similar to those for 2D MRE (0.89, 0.91, 0.94, and 0.92). Both the 2D and 3D MRE methods provided superior accuracy to the blood-based biomarkers, including APRI, FIB-4, and Forns index, especially for ≥ F2, ≥ F3, and F4 fibrosis stages (all p < 0.01). CONCLUSIONS: While 3D MRE offers certain advantages and opportunities for new applications of MRE, current widely deployed 2D MRE technology has comparable performance in the basic application of detecting and staging liver fibrosis. KEY POINTS: • 2D MRE and 3D MRE have comparable diagnostic performance in detecting and staging liver fibrosis. • 3D MRE has superior image quality and interobserver agreement compared to 2D MRE.

Differential state-dependent effects of deltamethrin and tefluthrin on sodium channels in central neurons of Helicoverpa armigera.

The cotton bollworm, Helicoverpa armigera is one of the worldwide pests. Electrophysiological properties of voltage-gated sodium channels in central neurons of sensitive and pyrethroid resistant H. armigera were investigated using whole-cell patch clamp technique. The modification effects of pyrethroid insecticides deltamethrin and tefluthrin on sodium channels were also compared. The V0.5 of voltage dependence of activation of resistant H. armigera sodium channels (resistant channels) exhibited an obvious depolarizing shift by 13.52 mV compared to that of sensitive H. armigera sodium channels (sensitive channels). In contrast, the V0.5 of the voltage dependence of steady-state inactivation of the resistant channels showed a significant hyperpolarizing shift by 7.59 mV in comparison with that of the sensitive channels. The time course of recovery from inactivation for the resistant channels was prolonged significantly, by 0.17 ms, compared with that for the sensitive channels. We also assessed the use-dependent effects of deltamethrin and tefluthrin on sensitive sodium channels. Repetitive depolarization remarkably increased the extent of the sensitive channel modification by 10 µM deltamethrin by ~4.61-fold but had no effect on the extent of sensitive channel modifications by 10 µM tefluthrin. These results provide more direct evidence for the presence of nerve insensitivity in resistant H. armigera strains in North of China. The sodium channels of the resistant H. armigera differ from those of the sensitive H. armigera in the fundamental electrophysiological properties, and correspondingly, have a different response to the modification of pyrethroids. Both deltamethrin and tefluthrin have effects on the closed state of the sensitive sodium channels, but deltamethrin has higher affinity to the open state of these channels.

Preoperative prediction of pathologic grade of HCC on gadobenate dimeglumine-enhanced dynamic MRI.

PURPOSE: To evaluate the value of gadobenate dimeglumine-enhanced MRI in predicting the pathologic grade of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients with pathologically proven HCC who underwent preoperative gadobenate dimeglumine-enhanced dynamic MRI were included. Two radiologists blinded to pathology results evaluated images in consensus. Lesions were evaluated quantitatively in terms of ratio of enhancement (RE), and qualitatively based on image features related to tumor aggressiveness. Logistic regression and ROC analyses were used to determine the value of these parameters to predict pathologic grade. RESULTS: In total, 221 patients (194 males, 27 females, aged 52.9 ± 11.7 years) with 49 poorly differentiated HCCs and 172 well/moderately differentiated HCCs were evaluated. Features significantly related to poorer pathologic grade at univariate analysis included lower RE in the early arterial phase (EAP) (p = 0.001), nonsmooth margins (p = 0.001), absence of capsule (p < 0.001), arterial peritumoral hyperenhancement (p < 0.001), higher AFP (p = 0.004), multiple tumors (p = 0.026), and larger tumor size (p = 0.028). At multivariate analysis, lower RE (EAP) (OR = 0.144, p = 0.002), absence of capsule (OR = 0.281, p = 0.004), and arterial peritumoral hyperenhancement (OR = 4.117, p < 0.001) were independent predictive factors for poorer pathologic grade. ROC analysis showed lower RE (EAP) was predictive of poorer pathologic grade (AUC = 0.667). AUC increased to 0.797 when combined with absence of capsule and presence of peritumoral hyperenhancement. CONCLUSIONS: Lower RE (EAP), absence of capsule, and arterial peritumoral hyperenhancement were predictive biomarkers for poorer pathologic grade of HCC on gadobenate dimeglumine-enhanced dynamic MRI. KEY POINTS: • Gadobenate dimeglumine-enhanced dynamic MRI was a useful quantitative biomarker for preoperative prediction of pathologic grade in patients with HCC. • Lower RE in the early arterial phase, absence of capsule, and arterial peritumoral hyperenhancement were potential imaging indicators for preoperative prediction of poorer pathologic grade of HCC on gadobenate dimeglumine-enhanced MRI. • A lower RE in the early arterial phase was effective at predicting poorer pathologic grade of HCCs but prediction is improved when combined with absence of capsule and presence of peritumoral hyperenhancement.

The role of lesion hypointensity on gadobenate dimeglumine-enhanced hepatobiliary phase MRI as an additional major imaging feature for HCC classification using LI-RADS v2018 criteria.

OBJECTIVES: To determine the value of lesion hypointensity in the hepatobiliary phase (HBP) on gadobenate dimeglumine-enhanced MRI as an additional major imaging feature for diagnosis of hepatocellular carcinoma (HCC) using LI-RADS v2018 criteria. METHODS: Between March 2016 and August 2018, 235 patients with 250 hepatic nodules at high risk of HCC underwent gadobenate dimeglumine-enhanced MRI. Two radiologists independently evaluated the imaging features and classified the nodules based on LI-RADS v2018 criteria, and their consensus data were used to calculate the diagnostic performance of LI-RADS categories. Two modified LI-RADS definitions were as follows: (1) LI-RADS-m1: HBP hypointensity as an additional major feature; (2) LI-RADS-m2: HBP hypointensity as an alternative to "enhancing capsule" as an additional major feature. The diagnostic performance of LR-5 categories was compared using McNemar's test. RESULTS: The sensitivity and specificity for LR-5 classification using original LI-RADS v2018 criteria were 78.1% and 96.3%, respectively. Significantly improved sensitivity (82.7%; p = 0.004) with unchanged specificity (96.3%; p = 1.00) was seen for LR-5 classification using LI-RADS-m1. Similar sensitivity and specificity (82.7% and 96.3%, respectively) were also seen using LI-RADS-m2. Significantly improved sensitivity (79.5% vs. 64.0%; p = 0.031) with unchanged specificity (96.2% vs. 96.2%, p = 1.00) was seen using both LI-RADS-m1 and LI-RADS-m2 compared to the original LI-RADS v2018 for 39 HCC nodules measuring 10-19 mm. CONCLUSIONS: Lesion hypointensity on gadobenate dimeglumine-enhanced HBP MRI may improve sensitivity for LR-5 classification beyond that achievable using conventional LI-RADS v2018 criteria. Lesion hypointensity may prove a suitable alternative imaging feature to enhancing capsule for accurate LR-5 classification. KEY POINTS: • Including lesion hypointensity in the HBP as an additional major feature improved sensitivity for LR-5 classification on gadobenate dimeglumine-enhanced MRI. • Lesion hypointensity in the HBP can replace "enhancing capsule" as an additional major feature for LR-5 classification without impairing specificity.

Evaluation of MR elastography for prediction of lymph node metastasis in prostate cancer.

PURPOSE: To assess the relationship between MRE stiffness of prostate cancer (PCa) and the extent of lymph node metastasis (LNM) in patients with PCa undergoing radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). MATERIALS: The local institutional review board approved this retrospective study. We retrospectively analyzed 49 patients, who had undergone MRE, mpMRI and pelvic MRI on a 3.0 T MRI scanner, with histopathological confirmed PCa after RP (from June 2015 to December 2019). For each patient, preoperative clinical data and characteristics of MRE, mpMRI and pelvic MRI were recorded. Independent-samples t test, univariate and multivariate logistic regression analyses were performed. And receiver operating characteristic (ROC) analysis were performed to compare the diagnostic performances of multivariate models with the Briganti 2019 nomogram. RESULTS: PCa MRE stiffness and maximum diameter were independent predictors of LNM. When PCa MRE stiffness at 60 Hz (odds ratio [OR] = 20.223, P = 0.013) and maximum diameter (OR = 4.575, P = 0.046) were combined, the sensitivity and specificity were 100% and 91.9% to predict LNM. When PCa MRE stiffness at 90 Hz (OR = 7.920, P = 0.013) and maximum diameter (OR = 2.810, P = 0.045) were combined, the sensitivity and specificity were 100% and 86.5% to predict LNM. The areas under curves (AUCs) of the combinations were higher than the AUC of the Briganti 2019 nomogram (0.982 vs. 0.904, P = 0.040 [60 Hz]; 0.975 vs. 0.904, P = 0.060 [90 Hz], respectively). CONCLUSIONS: MRE-based assessment of PCa stiffness may be useful for predicting LNM of PCa preoperatively and noninvasively.

Liver Imaging and Data System (LI-RADS) Version 2018 and Other Imaging Features in Intrahepatic Cholangiocarcinoma in Chinese Adults with vs. without Chronic Hepatitis B Viral Infection.

Purpose: To describe liver imaging reporting and data system (LI-RADS) version 2018 and other MRI imaging features in intrahepatic mass-forming cholangiocarcinoma (iCCA) in Chinese adults with vs. without chronic hepatitis B viral (HBV) infection. Methods: We retrospectively enrolled 89 patients with pathologically proven iCCA after multiphase imaging performed between 2004 and 2017 at a tertiary medical center in southern China. Based on whether patients had chronic HBV, iCCA was divided into two subgroups: HBV-positive (n = 50 patients, including 9 with cirrhosis) vs. HBV-negative (n = 39 patients, including 14 with hepatolithiasis and 25 with no identifiable risk factor for iCCA; none had cirrhosis). Two independent abdominal radiologists in consensus reviewed the largest mass in each patient to assign LI-RADS v2018 features; they also scored each observation's shape and location. Imaging features were compared using chi-square or Fisher's exact tests. Results: Most iCCAs in HBV-positive (88% (44/50)) and HBV-negative (97% (38/39)) patients had at least one LR-M feature. Compared to iCCAs in HBV-negative patients, iCCAs in HBV-positive patients were more likely to have at least one major feature of HCC (46% (23/50) vs. 8% (3/39), P < 0.001) and more likely to be smooth (42% (21/50) vs. 10% (4/39), P = 0.001). Six of 50 (12%) iCCAs in HBV-positive patients and 1/39 (3%) iCCAs in HBV-negative patients had at least one major feature of HCC without any LR-M feature. Conclusions: In this retrospective single-center study in Chinese adults, iCCAs in HBV-positive patients were more likely to resemble HCCs than iCCAs in HBV-negative patients.

Accuracies of Chemical Shift In/Opposed Phase and Chemical Shift Encoded Magnetic Resonance Imaging to Detect Intratumoral Fat in Hepatocellular Carcinoma.

BACKGROUND: Magnetic Resonance Imaging (MRI) being a noninvasive modality may help in preoperative evaluation of intratumoral fat in hepatocellular carcinoma (HCC) using chemical shift encoded (CSE) MRI and in-/opposed-phase (IOP) imaging sequences. PURPOSE: To compare the diagnostic accuracy of chemical shift encoded fat fraction at three different flip angles (FAs) using quantitative chemical shift encoded MRI (CSE-MRI) with in-/opposed phase (IOP) imaging to evaluate intratumoral fat in HCC. STUDY TYPE: Retrospective. POPULATION: Eighty-six patients with 87 pathology proven HCCs. FIELD STRENGTH/SEQUENCE: IOP (LAVA-Flex) and CSE-MRI (IDEAL IQ) a three-dimensional spoiled gradient-echo pulse sequences acquired at 3 T. ASSESSMENT: Regions of interest (ROIs) were manually drawn by two observers in the tumors to measure mean fat fractions. Surgical specimens were reassessed for intratumoral fat content. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were assessed for CSE-MRI sequence at FA 3°, 8°, and 9°. STATISTICAL TESTS: Intraclass correlation coefficient (ICC) was expressed in terms of inter- and intra-observer agreements. Receiver operating characteristic curve analysis was performed for the diagnostic performance followed by combined metric of both. SNR/CNR were analyzed by Kruskal-Wallis test. RESULTS: Excellent inter- and intra-observer agreements (ICC >0.95, P < 0.001) were observed for both IOP and CSE-MRI. IOP (86.4%) showed higher sensitivity than CSE-MRI at FA 3° (72.5%), FA 8° (76.4%) and FA 9° (76.3%). In contrast, the specificity for CSE-MRI at FA 3° (86%), FA 8° (87%), and FA 9° (87%) were greater than IOP (72%). A combined metric of IOP and CSE-MRI derived fat fractions at FA 8° gave highest AUC of 87% and accuracy of 86%. SNR and CNR for CSE-MRI were significantly higher at FA 8° and FA 9° than FA 3° (P < 0.05). DATA CONCLUSION: IOP and quantitative CSE-MRI are both feasible methods to detect intratumoral fat in HCC with higher accuracy and SNR for CSE-MRI at FA 8° and 9°. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Increasing the sensitivity of LI-RADS v2018 for diagnosis of small (10-19 mm) HCC on extracellular contrast-enhanced MRI.

PURPOSE: To evaluate whether the LI-RADS v2018 LR-5 criteria can be modified to increase sensitivity without reducing specificity for diagnosing small (10-19 mm) HCC. METHODS: 167 consecutive high-risk patients with 174 small observations reported clinically on extracellular contrast-enhanced MRI from 2014 to 2018 were retrospectively studied. The best available reference standard was applied for each observation. Blinded to the reference standard, two radiologists scored LI-RADS imaging features retrospectively and assigned each observation a LI-RADS category using LI-RADS v2018 and each of four modified LI-RADS versions (mLI-RADS I to IV) with successively more expansive LR-5 criteria. Per-observation sensitivity and specificity of LR-5 for small HCC using each version were assessed. Each modified version was compared to v2018 (McNemar test). RESULTS: The 174 observations included 135 HCC, 8 non-HCC malignancies, and 31 benign entities. Using LI-RADS v2018, LR-5 provided 70% (both readers) sensitivity and 95% (both readers) specificity for small HCC. Expanding the LR-5 criteria to include nonrim APHE plus at least one additional major feature (mLI-RADS I) or no APHE plus at least two additional major features (mLI-RADS II) significantly increased sensitivity (reader 1/reader 2: 75%/75% vs. 70%, p = 0.016/0.031; 78%/79% vs. 70%, p = 0.001/0.001) without significantly reducing specificity (reader 1/reader 2: 90%/92% vs. 95%, p = 0.500/1.000 for both). mLI-RADS III and IV further increased sensitivity (reader 1/reader 2: 80%/81% vs. 70%, p < 0.001/< 0.001; 94%/92% vs. 70, p < 0.001/< 0.001) but with trend-level (reader 1/reader 2: 85%/80% vs. 95%, p = 0.125/0.063) or significant (reader 1/reader 2: 64%/62% vs. 95%, p < 0.001/< 0.001) specificity reductions. CONCLUSIONS: Expanding the v2018 LR-5 criteria to include nonrim APHE plus at least one additional major feature or no APHE plus at least two additional major features significantly increases sensitivity without significantly reducing specificity for small HCC. Confirmation is warranted in multi-center prospective studies.

Pain- and Fatigue-Related Functional and Structural Changes in Ankylosing Spondylitis: An fRMI Study.

Background: Chronic pain and fatigue are two cardinal features of ankylosing spondylitis (AS) and how to effectively treat these conditions continues to be a challenge. The underlying mechanisms and the relationship between AS-related pain and fatigue remain poorly understood. The present study was conducted, therefore, to explore the brain functional and structural changes associated with pain and fatigue in AS. Methods: A total of 65 AS patients (48 men and 17 women; 32.33 ± 8.6 years) and 53 age- and sex-matched controls were enrolled in the study. The patients underwent clinical assessment based on Total Back Pain scores, Fatigue Severity Scale, Bath Ankylosing Spondylitis Disease Activity Index, (BASDAI), high-sensitivity C-reactive Protein (hsCRP), erythrocyte sedimentation rate (ESR), and Beck Depression Inventory (BDI). Using 3T magnetic resonance imaging (3T-MRI), we analyzed the brain functional (connectivity and nodal properties) and structural (covariance and gray matter volumes) differences between AS patients and controls. Furthermore, we extracted the values of the significantly changed regions in the AS cohort and explored their association with pain and fatigue. Results: In AS patients, there were functional and structural abnormalities distributed in the default mode network (DMN), salience network (SN), sensory/somatomotor network (SMN), dorsal attention network (DAN), task control network (TCN), and visual network, and some regions showed both types of changes. Among these, the functional connectivity (FC) between the left insula and medial prefrontal cortex, the betweenness centrality of the left medial prefrontal cortex and the gray matter volume of the right putamen tracked both pain and fatigue. In addition, pain was related to within-DMN FC disruption and nodal function / gray matter volumes changes in DMN, SN, and the visual network, while fatigue mainly involved the SMN, DAN, and TCN. Moreover, certain changes were also related to BASDAI and inflammation level. Conclusion: This study offers new insights into understanding the neural mechanism of AS-related pain and fatigue, and could help to stratify patients based on the correlation features and ultimately move towards a personalized therapy.

Real-time ultrasonography-magnetic resonance image fusion navigation for percutaneous transforaminal endoscopic discectomy.

OBJECTIVE: Percutaneous transforaminal endoscopic discectomy (PTED) is usually performed under fluoroscopic guidance and is associated with a large radiation dose. Ultrasonography (US)-MR image fusion navigation combines the advantages of US and MRI and requires significantly less radiation than fluoroscopy. The purpose of this study was to evaluate the safety and effectiveness of US-MR image fusion navigation for PTED. METHODS: From January to September 2018, patients with L4-5 lumbar disc herniation requiring PTED were randomized to have the procedure conducted with US-MR image fusion navigation or fluoroscopy. The number of fluoroscopies, radiation dose, duration of imaging guidance, intraoperative visual analog scale (VAS) pain score, intraoperative complications, and clinical outcomes were compared between the groups. RESULTS: There were 10 patients in the US-MR navigation group and 10 in the fluoroscopy group, and there were no significant differences in age, sex ratio, or BMI between the 2 groups (all p > 0.05). Intraoperatively, the total radiation dose, number of fluoroscopies performed, duration of image guidance, and VAS low-back and leg pain scores were all significantly lower in the US-MRI navigation group than in the fluoroscopy group (all p < 0.05). There were no intraoperative complications in either group. Postoperative improvements in Japanese Orthopaedic Association, Oswestry Disability Index, and VAS pain scale scores were similar between the 2 groups. CONCLUSIONS: US-MR image fusion navigation is a promising technology for performing PTED and requires significantly less radiation than fluoroscopy.Clinical trial registration no.: NCT03403244 (ClinicalTrials.gov).

A comparative study of monoexponential versus biexponential models of diffusion-weighted imaging in differentiating histologic grades of hepatitis B virus-related hepatocellular carcinoma.

PURPOSE: To compare the diagnostic value of apparent diffusion coefficient (ADC) and intravoxel incoherent motion metrics in discriminating histologic grades of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) infection. METHODS: 117 chronic HBV patients with 120 pathologically confirmed HCCs after surgical resection or liver transplantation were enrolled in this retrospective study. Diffusion-weighted imaging was performed using eleven b values (0-1500 s/mm2) and two b values (0, 800 s/mm2) successively on a 3.0 T system. ADC0, 800, ADCtotal, diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were calculated. The parameters of three histologically differentiated subtypes were investigated using Kruskal-Wallis test, Spearman rank correlation, and receiver-operating characteristic analysis. Interobserver agreement was assessed using the intraclass correlation coefficient. RESULTS: There was excellent agreement for ADCtotal/D/f, good agreement for ADC0,800, and moderate agreement for D*. ADCtotal, ADC0, 800,D, and f were significantly different for well, moderately, and poorly differentiated HCCs (P < 0.001), and they were all inversely correlated with histologic grades: r = - 0.633, - 0.394, - 0.435, and - 0.358, respectively (P < 0.001). ADCtotal demonstrated higher performance than ADC0,800 in diagnosing both well and poorly differentiated HCCs (P < 0.001 and P = 0.04, respectively). ADCtotal showed higher performance than D and f in diagnosing well differentiated HCCs (P < 0.001) and similar performance in diagnosing poorly differentiated HCCs (P = 0.06 and 0.13, respectively). CONCLUSIONS: ADCtotal showed better diagnostic performance than ADC0,800, D, and f to discriminate histologic grades of HCC.

RBAK is upregulated in non-small cell lung cancer and promotes cell migration and invasion.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-associated mortality worldwide, NCSCLC includes lung adenocarcinoma and lung squamous cell carcinoma. Tumor metastasis is the major cause of mortality of patients with NSCLC. However, the mechanisms underlying NSCLC metastasis remain largely elusive. In present study, the authors focused on exploring the roles of RBAK in NSCLC. The present study demonstrated that RB-associated KRAB zinc finger (RBAK) was upregulated in NSCLC compared with non-tumorous tissues by analyzing Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) dataset. High expression of RBAK was associated with poor disease-free survival of patients with NSCLC by analyzing TCGA dataset. Furthermore, an RBAK-mediated protein-protein interaction network was constructed to reveal the potential underlying mechanisms by which RBAK drives NSCLC progression. The authors found that RBAK was involved in regulating a number of transcription factors, including androgen receptor, forkhead box A1, tumor protein 53, and E2F transcription factor 1, 2 and 4, suggesting that RBAK may have a role in regulating gene transcription. GO and KEGG enrichment analyses of the genes co-expressed with RBAK revealed that RBAK is involved in regulating a number of biological functions, including the Wnt signaling pathway, mRNA splicing, protein polyubiquitination, cell-cell adhesion and focal adhesion. Transwell and wound healing assays demonstrated that knockdown of RBAK suppressed NSCLC cell migration and invasion. The present study enhances the current understanding of the important roles of RBAK in NSCLC metastasis and may provide useful information for the development of novel treatment approaches.

Liver Imaging Reporting and Data System Category 5: MRI Predictors of Microvascular Invasion and Recurrence After Hepatectomy for Hepatocellular Carcinoma.

OBJECTIVE. We investigated in Liver Imaging Reporting and Data System category 5 (LR-5) observations whether imaging features, including LI-RADS imaging features, could predict microvascular invasion (MVI) and posthepatectomy recurrence in high-risk adult patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS. We retrospectively identified 149 high-risk patients who underwent 3-T MRI within 1 month before hepatectomy for HCC; 81 of 149 patients with no HCC recurrence were followed for more than 1 year. Tumors with clear surgical margins were confirmed in each hepatectomy specimen. MVI was evaluated histologically by a histopathologist. Tumor recurrence was determined by clinical and imaging follow-up. Two independent radiologists reviewed the prehepatectomy MR images and assessed LI-RADS v2018 imaging features as well as some non-LI-RADS features in all LR-5 observations in consensus. Alpha-fetoprotein level, tumor number, and imaging features were analyzed as potential predictors for MVI and posthepatectomy recurrence using multivariate logistic regression and Cox proportional hazards models. RESULTS. One hundred forty-nine patients with pathologically confirmed HCC were included; 64 of 149 (43.0%) patients had MVI, whereas 48 of 129 (37.2%) patients had tumor recurrence within 3 years after hepatectomy. Mosaic architecture (odds ratio, 3.420; p < 0.001) and nonsmooth tumor margin (odds ratio, 2.554; p = 0.011) were independent predictors of MVI. Multifocal tumors (hazard ratio, 2.101; p = 0.034), absence of fat in mass (hazard ratio, 2.109; p = 0.015), and nonsmooth tumor margin (hazard ratio, 2.415; p = 0.005) were independent predictors of posthepatectomy recurrence. CONCLUSION. In high-risk patients with LR-5 HCC, mosaic architecture and non-smooth tumor margin independently predicted MVI. Multifocal tumors, absence of fat in mass, and nonsmooth tumor margin independently predicted recurrence.

Can IVIM help predict HCC recurrence after hepatectomy?

PURPOSE: To determine the diagnostic performance of intravoxel incoherent motion (IVIM) parameters to predict tumor recurrence after hepatectomy in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). MATERIALS AND METHODS: One hundred and fifty-seven patients (mean age 52.54 ± 11.32 years, 87% male) with surgically and pathologically confirmed HCC were included. Regions of interests were drawn including the tumors by two independent radiologists. ADC and IVIM-derived parameters (true diffusion coefficient [D]; pseudodiffusion coefficient [D*]; pseudodiffusion fraction [f]) were obtained preoperatively. The Cox proportional hazards model was used to analyze the predictors associated with tumor recurrence after hepatectomy. RESULTS: Forty-seven of 157 (29.9%) patients experienced tumor recurrence. The multivariate Cox proportional hazards model revealed that a D value < 0.985 × 10-3 mm2/s (hazard ratio (HR), 0.190; p = 0.023) was a risk factor for tumor recurrence. Additional risk factors included younger age (HR, 0.328; p = 0.034) and higher serum alpha-fetoprotein (AFP) level (HR, 2.079; p = 0.013). Further, receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of the obtained Cox regression model improved from 0.68 for the combination of AFP and age alone to 0.724 for the combination of D value, AFP, and age. CONCLUSION: The D value derived from the IVIM model is a potential biomarker for the preoperative prediction of recurrence after hepatectomy in patients with HCC. When combined with age and AFP levels, D can improve the predictive performance for tumor recurrence. KEY POINTS: • The recurrence rate of HCC after hepatectomy was higher in patients with ADC, D, and f values that were lower than the optimal cutoff values. • The optimal cutoff values of ADC, D, D*, and f for predicting recurrence in HBV associated HCC were 0.858 × 10-3 mm2/s, 0.985 × 10-3 mm2/s, 12.5 × 10-3 mm2/s, and 23.4%, respectively. • The D value derived from IVIM diffusion-weighted imaging may be a useful biomarker for preoperative prediction of recurrence after hepatectomy in patients with HCC. When combined with age and AFP levels, D can improve the predictive performance for tumor recurrence.