Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion Maternal Vaccine Coadministered With Diphtheria-Tetanus-Pertussis Vaccine: A Phase 2 Study.

BACKGROUND: Respiratory syncytial virus (RSV) fusion protein stabilized in the prefusion conformation (RSVPreF3) was under investigation as a maternal vaccine. METHODS: This phase 2, randomized, placebo-controlled, single-dose, multicenter study enrolled healthy, nonpregnant women, randomized 1:1:1:1:1 to 5 parallel groups studying RSVPreF3 (60 or 120 µg) coadministered with diphtheria, tetanus, and acellular pertussis vaccine (dTpa) or placebo, and dTpa coadministered with placebo. Safety and humoral immune responses were assessed. An extension phase also assessed a RSVPreF3 120 µg vaccination 12-18 months after first vaccination. RESULTS: The safety profile of RSVPreF3 was unaffected by dose or dTpa coadministration. Solicited and unsolicited adverse events (AEs) were evenly distributed across study groups. Injection-site pain was higher following the second vaccination versus the first vaccination. Medically attended AEs were rare (<5% overall). Both RSVPreF3 dose levels (alone and with dTpa) were immunogenic, increasing levels of RSV-A neutralizing antibody ≥8-fold and anti-RSVPreF3 IgG antibody ≥11-fold at 1 month postvaccination, which persisted at 12-18 months postvaccination; modest 2-fold increases were observed with a second RSVPreF3 vaccination. CONCLUSIONS: This study indicates RSVPreF3 coadministration with dTpa induces robust immune responses and is well tolerated, regardless of the RSVPreF3 dose level used. CLINICAL TRIALS REGISTRATION: NCT04138056.

Multiphase MRI-Based Radiomics for Predicting Histological Grade of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer. Accurate preoperative prediction of histological grade holds potential for improving clinical management and disease prognostication. PURPOSE: To evaluate the performance of a radiomics signature based on multiphase MRI in assessing histological grade in solitary HCC. STUDY TYPE: Retrospective. SUBJECTS: A total of 405 patients with histopathologically confirmed solitary HCC and with liver gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI within 1 month of surgery. FIELD STRENGTH/SEQUENCE: Contrast-enhanced T1-weighted spoiled gradient echo sequence (LAVA) at 1.5 or 3.0 T. ASSESSMENT: Tumors were graded (low/high) according to results of histopathology. Basic clinical characteristics (including age, gender, serum alpha-fetoprotein (AFP) level, history of hepatitis B, and cirrhosis) were collected and tumor size measured. Radiomics features were extracted from Gd-EOB-DTPA-enhanced MRI data. Three feature selection strategies were employed sequentially to identify the optimal features: SelectFromModel (SFM), SelectPercentile (SP), and recursive feature elimination with cross-validation (RFECV). Probabilities of five single-phase radiomics-based models were averaged to generate a radiomics signature. A combined model was built by combining the radiomics signature and clinical predictors. STATISTICAL TESTS: Pearson χ2 test/Fisher exact test, Wilcoxon rank sum test, interclass correlation coefficient (ICC), univariable/multivariable logistic regression analysis, area under the receiver operating characteristic (ROC) curve (AUC), DeLong test, calibration curve, Brier score, decision curve, Kaplan-Meier curve, and log-rank test. A P-value <0.05 was considered statistically significant. RESULTS: High-grade HCCs were present in 33.8% of cases. AFP levels (odds ratio [OR] 1.89) and tumor size (>5 cm; OR 2.33) were significantly associated with HCC grade. The combined model had excellent performance in assessing HCC grade in the test dataset (AUC: 0.801), and demonstrated satisfactory calibration and clinical utility. DATA CONCLUSION: A model that combined a radiomics signature derived from preoperative multiphase Gd-EOB-DTPA-enhanced MRI and clinical predictors showed good performance in assessing HCC grade. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 5.

Hepatobiliary phase imaging in cirrhotic patients using compressed sensing and controlled aliasing in parallel imaging results in higher acceleration.

OBJECTIVE: We aimed to compare the image quality and focal lesion detection ability of hepatobiliary phase (HBP) images obtained using compressed sensing (CS) and controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) in patients with liver cirrhosis. MATERIALS AND METHODS: We retrospectively included 244 gadoxetic acid-enhanced liver MRI from 244 patients with cirrhosis obtained by two HBP images using CS and CAIPIRINHA from July 2020 to December 2020. The optimized resolution and scan time for CS-HBP and CAIPIRINHA-HBP were 0.9 × 0.9 × 1.5 mm3 and 15 s and 1.3 × 1.3 × 3 mm3 and 16 s, respectively. We compared the image quality between the two sets of images in 244 patients and focal lesion (n = 294) analyses for 112 patients. RESULTS: CS-HBP showed comparable overall image quality (3.7 ± 0.9 vs. 3.6 ± 0.8, p = 0.680), superior liver edge sharpness (3.9 ± 0.6 vs. 3.6 ± 0.5, p < 0.001), and fewer respiratory motion artifacts (4.0 ± 0.7 vs. 3.8 ± 0.5, p < 0.001), but higher non-respiratory artifacts (3.4 ± 0.7 vs. 3.6 ± 0.6, p < 0.001) and subjective image noise (3.5 ± 0.8 vs. 3.6 ± 0.7, p = 0.014) than CAIPIRINHA-HBP. CS-HBP showed a higher signal-to-noise ratio in the liver than CAIPIRINHA-HBP (20.9 ± 9.0 vs. 18.9 ± 7.1, p = 0.008). The pooled sensitivity, specificity, and AUC were 90.0%, 77.5%, and 0.84 for CS-HBP and 73.5%, 82.4%, and 0.78 for CAIPIRINHA-HBP, respectively. CONCLUSIONS: CS-HBP showed better focal lesion detection ability, comparable overall image quality, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and noise compared to CAIPIRINHA-HBP. Thus, CS-HBP could be recommended for liver MRI in patients with cirrhosis to improve diagnostic performance. CLINICAL RELEVANCE STATEMENT: Thin-slice CS-HBP may be useful for detecting sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A while maintaining comparable subjective image quality. KEY POINTS: • Compared with controlled aliasing in parallel imaging results in higher acceleration, compressed sensing hepatobiliary phase yielded thinner slices and shorter scan time at a higher accelerating factor. • Compressed sensing hepatobiliary phase showed comparable overall image quality, superior liver edge sharpness, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and subjective image noise than controlled aliasing in parallel imaging results in higher acceleration-hepatobiliary phase. • Compressed sensing hepatobiliary phase can detect sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A.

Diagnostic algorithm for subcentimeter hepatocellular carcinoma using alpha-fetoprotein and imaging features on gadoxetic acid-enhanced MRI.

OBJECTIVE: To investigate the role of serum alpha-fetoprotein (AFP) in diagnosing subcentimeter hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI (EOB-MRI). METHODS: This study retrospectively enrolled treatment-naïve patients with chronic hepatitis B who had a solitary subcentimeter observation on EOB-MRI from January 2017 to March 2023. Final diagnosis was confirmed by pathology for HCC and pathology or follow-up for benign controls. The AFP cutoff value for HCC was determined using Youden's index. Diagnostic criteria were developed according to significant findings in logistic regression analyses based on AFP and imaging features. The diagnostic performance of possible criteria was compared to the diagnostic hallmarks of HCC (arterial-phase hyperintensity and portal-phase hypointensity). RESULTS: A total of 305 patients (mean age, 51.5 ± 10.7 years; 153 men) were divided into derivation and temporal validation cohorts. Four findings, namely AFP >13.7 ng/mL, arterial-phase hyperintensity, portal-phase hypointensity, and transitional-phase hypointensity, were predictors of HCC. A new criterion (at least three of the four findings) showed higher sensitivity than the diagnostic hallmarks (derivation cohort, 71.6% vs. 52.3%, p < 0.001; validation cohort, 75.0% vs. 47.5%, p = 0.003) without decreasing specificity (derivation cohort, 92.5% vs. 92.5%, p > 0.999; validation cohort, 92.0% vs. 92.0%, p > 0.999). Another criterion (all four findings) achieved a slightly higher specificity than the diagnostic hallmark (derivation cohort, 99.1% vs. 92.5%, p = 0.023; validation cohort, 100.0% vs. 92.0%, p = 0.134). Subgroup analysis for hepatobiliary hypointense observations yielded similar results. CONCLUSION: Including AFP in the diagnostic algorithm may improve the diagnostic performance for subcentimeter HCC. CLINICAL RELEVANCE STATEMENT: Combining imaging features on gadoxetic acid-enhanced MRI with alpha-fetoprotein may enhance the diagnostic performance for subcentimeter HCC in treatment-naïve patients with chronic hepatitis B. KEY POINTS: • The traditional diagnostic hallmark of HCC (arterial-phase hyperintensity and portal-phase hypointensity) shows modest diagnostic performance for subcentimeter HCC on EOB-MRI. • Serum alpha-fetoprotein > 13.7 ng/mL, arterial-phase hyperintensity, portal-phase hypointensity, and transitional-phase hypointensity were independent predictors for subcentimeter HCC. • A criterion of at least three of the four above findings achieved a higher sensitivity without decreasing specificity.

Suboptimal performance of LI-RADS v2018 on gadoxetic acid-enhanced MRI for detecting hepatocellular carcinoma in liver transplant candidates.

OBJECTIVES: To evaluate the diagnostic performance for hepatocellular carcinoma (HCC) detection of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 on gadoxetic acid-enhanced MRI, comparing liver transplant candidates (LT group) with patients who underwent surgical resection (SR group), and to determine significant clinical factors for diagnostic performance of LI-RADS v2018. METHODS: Patients who underwent gadoxetic acid-enhanced MRI and subsequent SR or LT for HCC were retrospectively included between January 2019 and December 2020. The sensitivity and specificity of LI-RADS LR-5 for HCC were compared between the two groups using generalized estimating equations. The accuracy of patient allocation according to the Milan criteria was calculated for the LT group. Univariable and multivariable logistic regression analyses were performed to determine significant clinical factors associated with the sensitivity of LI-RADS. RESULTS: Of the 281 patients, 237 were assigned to the SR group, and 44 were assigned to the LT group. The LT group showed significantly lower per-patient (48.5% vs. 79.6%, p < .001) and per-lesion sensitivity (31.0% vs. 75.9%, p < .001) than the SR group, whereas no significant difference in both per-patient (100.0% vs. 91.7%, p > .99) and per-lesion specificities (100.0% vs. 94.1%, p > .99). The accuracy of patient allocation was 50.0%. Sensitivity was significantly lower in patients with a smaller lesion size (p < .001), a larger lesion number (p = .002), and a higher Child-Pugh score (p = .009). CONCLUSION: LI-RADS v2018 on gadoxetic acid-enhanced MRI might be insufficient in liver transplant candidates and other diagnostic imaging tests should be considered in patients with these significant clinical factors. CLINICAL RELEVANCE STATEMENT: In liver transplant candidates with a smaller lesion size, a larger lesion number, and a higher Child-Pugh score, imaging tests other than gadoxetic acid-enhanced MRI may be clinically useful to determine the transplant eligibility. KEY POINTS: • The sensitivity of the Liver Imaging Reporting and Data System (LI-RADS) was lower in liver transplant candidates than in those who underwent surgical resection. • With the use of gadoxetic acid-enhanced MRI, the accuracy of patient allocation for liver transplantation on the basis of the Milan criteria was suboptimal. • The sensitivity of LI-RADS v2018 was significantly associated with lesion size, lesion number, and Child-Pugh classification.

Lesions hyper- to isointense to surrounding liver in the hepatobiliary phase of gadoxetic acid-enhanced MRI.

OBJECTIVES: Hyper- or isointensity in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI has high specificity for focal nodular hyperplasia (FNH) but may be present in hepatocellular adenoma and carcinoma (HCA/HCC). This study aimed to identify imaging characteristics differentiating FNH and HCA/HCC. MATERIALS AND METHODS: This multicenter retrospective cohort study included patients with pathology-proven FNH or HCA/HCC, hyper-/isointense in the HBP of gadoxetic acid-enhanced MRI between 2010 and 2020. Diagnostic performance of imaging characteristics for the differentiation between FNH and HCA/HCC were reported. Univariable analyses, multivariable logistic regression analyses, and classification and regression tree (CART) analyses were conducted. Sensitivity analyses evaluated imaging characteristics of B-catenin-activated HCA. RESULTS: In total, 124 patients (mean age 40 years, standard deviation 10 years, 108 female) with 128 hyper-/isointense lesions were included. Pathology diagnoses were FNH and HCA/HCC in 64 lesions (50%) and HCA/HCC in 64 lesions (50%). Imaging characteristics observed exclusively in HCA/HCC were raster and atoll fingerprint patterns in the HBP, sinusoidal dilatation on T2-w, hemosiderin, T1-w in-phase hyperintensity, venous washout, and nodule-in-nodule partification in the HBP and T2-w. Multivariable logistic regression and CART additionally found a T2-w scar indicating FNH, less than 50% fat, and a spherical contour indicating HCA/HCC. In our selected cohort, 14/48 (29%) of HCA were B-catenin activated, most (13/14) showed extensive hyper-/isointensity, and some had a T2-w scar (4/14, 29%). CONCLUSION: If the aforementioned characteristics typical for HCA/HCC are encountered in lesions extensively hyper- to isointense, further investigation may be warranted to exclude B-catenin-activated HCA. CLINICAL RELEVANCE: Hyper- or isointensity in the HBP of gadoxetic acid-enhanced MRI is specific for FNH, but HCA/HCC can also exhibit this feature. Therefore, we described imaging patterns to differentiate these entities. KEY POINTS: FNH and HCA/HCC have similar HBP intensities but have different malignant potentials. Six imaging patterns exclusive to HCA/HCC were identified in this lesion population. These features in liver lesions hyper- to isointense in the HBP warrant further evaluation.

Comparison of cystatin C-based estimated glomerular filtration rate with measured glomerular filtration rate in a pediatric cohort of patients with chronic kidney disease.

BACKGROUND: It is essential to have an accurate assessment of the renal function of patients with chronic kidney disease to monitor, treat, and predict further development of the condition. Measurement of renal function in terms of glomerular filtration rate (GFR) requires either urine or blood sampling, but especially in children, more simple methods of measurement are preferable. The main objective of this study was to examine if the estimated GFR (eGFR) calculated with different cystatin-C-based equations was comparable to the GFR measured by a radiotracer (mGFR) in pediatric patients. METHODS: In this retrospective study, 28 pediatric patients contributed with 73 pairs of measurements collected within 5 years. Bland-Altman Limits of Agreement were used to evaluate the performance and accuracy of two different cystatin-C-based estimates, the CKiDCrea-CysC and the CKiDU25 respectively, compared to an mGFR based on plasma clearance of technetium-99m-diethylenetriaminepentaacetic acid or chromium-51-ethylenediaminetetraacetic acid. RESULTS: Using the CKiDCrea-CysC equation, 58.9% of the datasets were within P10 and 87.7% were within P30. The mean difference was 4.8 mL/min/1.73m2 (standard deviation: 8.5 mL/min/1.73m2) and tended to overestimate GFR and thereby overrate the kidney function within the entire GFR range. Using the CKiDU25 equation, 53.4% were within P10 and 93.2% within P30. The mean difference was -2.9 mL/min/1.73m2 (standard deviation: 8.4 mL/min/1.73m2), but the difference varied with the GFR value. CONCLUSIONS: A cystatin-C-based eGFR provides a viable substitute for monitoring renal function in pediatric patients with chronic kidney disease. However, it has a lower accuracy than mGFR and can therefore not replace mGFR in clinical use.

Assessment of hepatic transporter function in rats using dynamic gadoxetate-enhanced MRI: a reproducibility study.

OBJECTIVE: Previous studies have revealed a substantial between-centre variability in DCE-MRI biomarkers of hepatocellular function in rats. This study aims to identify the main sources of variability by comparing data measured at different centres and field strengths, at different days in the same subjects, and over the course of several months in the same centre. MATERIALS AND METHODS: 13 substudies were conducted across three facilities on two 4.7 T and two 7 T scanners using a 3D spoiled gradient echo acquisition. All substudies included 3-6 male Wistar-Han rats each, either scanned once with vehicle (n = 76) or twice with either vehicle (n = 19) or 10 mg/kg of rifampicin (n = 13) at follow-up. Absolute values, between-centre reproducibility, within-subject repeatability, detection limits, and effect sizes were derived for hepatocellular uptake rate (Ktrans) and biliary excretion rate (kbh). Sources of variability were identified using analysis of variance and stratification by centre, field strength, and time period. RESULTS: Data showed significant differences between substudies of 31% for Ktrans (p = 0.013) and 43% for kbh (p < 0.001). Within-subject differences were substantially smaller for kbh (8%) but less so for Ktrans (25%). Rifampicin-induced inhibition was safely above the detection limits, with an effect size of 75 ± 3% in Ktrans and 67 ± 8% in kbh. Most of the variability in individual data was accounted for by between-subject (Ktrans = 23.5%; kbh = 42.5%) and between-centre (Ktrans = 44.9%; kbh = 50.9%) variability, substantially more than the between-day variation (Ktrans = 0.1%; kbh = 5.6%). Significant differences in kbh were found between field strengths at the same centre, between centres at the same field strength, and between repeat experiments over 2 months apart in the same centre. DISCUSSION: Between-centre bias caused by factors such as hardware differences, subject preparations, and operator dependence is the main source of variability in DCE-MRI of liver function in rats, closely followed by biological between-subject differences. Future method development should focus on reducing these sources of error to minimise the sample sizes needed to detect more subtle levels of inhibition.

Enhancing oral bioavailability of Ca-DTPA by self double emulsifying drug delivery system (SDEDDS).

OBJECTIVE: BCS class III drug (highly soluble, poorly permeable) possesses low oral bioavailability. The research work highlights the utility of self-double emulsifying drug delivery system (SDEDDS) which are stable isotropic mixture of w/o primary emulsion and hydrophilic surfactants for improving oral bioavailability of Ca-DTPA (Calcium diethylenetriamine pentaacetate). Upon oral administration, SDEDDS rapidly emulsifies into w/o/w double emulsions in the aqueous gastrointestinal environment, with hydrophilic drugs entrapped inside oil reservoirs. METHODS: SDEDDS formulation was successfully developed using excipients, that is, medium chain triglycerides, oleic acid, phospholipids, Span 80, Tween 80 using double emulsification technique. RESULTS: The optimized formulation F4 (Aq. phase: 11.6%w,w; MCT & oleic acid: 70.9%w/w; Span 80:17.5%w/w; Lecithin:16%w/w and Tween 80 (10%w/w)) appeared bright yellow liquid which upon dilution appeared milky white within 2 min, droplet size (501.7 nm), pdi value (0.044), zeta potential (-52 mV), entrapment efficiency (79.6 ± 1.63), viscosity (72.2 ± 1.8 mpA.s), significant high cumulative in vitro drug permeation (CDP) and 2.17-fold increase in apparent permeability coefficient. Pharmacokinetic studies in rats showed 1.17-fold increases in AUC of F4 and comparatively higher plasma levels (Cmax) compared with pure drug administered orally. The Absolute (OF4, OD) and Relative bioavailability was found to be 14.52%, 12.35%, and 117.47%, respectively. CONCLUSION: The present studies have clearly demonstrated that SDEDDS could readily form w/o/w double emulsions in vivo with enhanced in vitro and in vivo oral bioavailability. Therefore, considerable augmentation in the rate and extent of oral drug absorption ratified the better performance of the SDEDDS in enhancing the bioavailability of Ca-DTPA.

In vivo labeling and quantitative imaging of neuronal populations using MRI.

The study of neural circuits, which underlies perception, cognition, emotion, and behavior, is essential for understanding the mammalian brain, a complex organ consisting of billions of neurons. To study the structure and function of the brain, in vivo neuronal labeling and imaging techniques are crucial as they provide true physiological information that ex vivo methods cannot offer. In this paper, we present a new strategy for in vivo neuronal labeling and quantification using MRI. We demonstrate the efficacy of this method by delivering the oatp1a1 gene to the target neurons using rAAV2-retro virus. OATP1A1 protein expression on the neuronal membrane increased the uptake of a specific MRI contrast agent (Gd-EOB-DTPA), leading to hyperintense signals on T1W images of labeled neuronal populations. We also used dynamic contrast enhancement-based methods to obtain quantitative information on labeled neuronal populations in vivo.

Bi-DTPA, a potential CT-guided radiation sensitizer.

The therapeutic effects and application of radiotherapy are restricted to some extent due to low radiosensitivity of tumor tissues and adverse effects by excess dosage. Current radiosensitizers are confronted with problems in clinical translation because of complicated manufacture technique and high cost. In this research, we have synthesized a radiosensitizer with advantages in low cost and mass production, which could be applied to CT imaging and enhanced radiotherapy in breast cancer, namely Bi-DTPA. It not only enhanced tumor CT imaging which resulted in better therapeutic accuracy, but also realized radiotherapy sensitization by producing massive ROS and inhibit tumor proliferation, providing a sound perspective in the clinical translation of the radiosensitizer.

Visualization Score of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging: The Effect on the Diagnostic Accuracy for Hepatocellular Carcinoma.

BACKGROUND: The visualization score of hepatobiliary-phase (HBP) images has been introduced as an image quality index for gadoxetic acid-enhanced MRI. It may be associated with hepatic function and could have an implication on the diagnostic accuracy for hepatocellular carcinoma (HCC). PURPOSE: To investigate the association between the visualization score of gadoxetic acid-enhanced MRI and clinical factors and to evaluate its effect on the diagnostic accuracy for HCC ≤ 3.0 cm. STUDY TYPE: Retrospective. POPULATION: A total of 493 focal lesions from 397 patients. FIELD STRENGTH/SEQUENCE: A 5-T or 3.0 -T with pre/postcontrast T1-weighted 3D gradient echo sequence, and T2-weighted fast spin-echo sequence ASSESSMENT: Child-Pugh classification and albumin-bilirubin (ALBI) score were assessed. Three readers evaluated the visualization score of each MRI examination (A, no or minimal; B, moderate; and C, severe limitations), and major features (arterial-phase hyperenhancement, washout, enhancing capsule, threshold growth) and ancillary features of each focal lesion. STATISTICAL TESTS: Univariable and multivariable logistic regression analyses were performed to determine significant clinical factors associated with a suboptimal visualization score (B or C). Generalized estimating equations were used to compare the sensitivity and specificity for diagnosing HCC between the two group (visualization score A vs. B or C). A P value < 0.05 was considered statistically significant. RESULTS: Of the 397 MRI examinations, the incidence of suboptimal visualization score was 13%. A suboptimal visualization score was significantly associated with Child-Pugh classification B or C (adjusted odds ratio [OR] = 15.2) and ALBI grade 2 or 3 (OR = 4.7). Compared with the visualization score A group, the suboptimal visualization score group showed significantly lower sensitivity (56.8% vs. 75.2%) and less frequent washout in HCC (62.2% vs. 84.0%). DATA CONCLUSION: The visualization score on gadoxetic acid-enhanced MRI can be an important image quality index and the diagnostic accuracy for HCC ≤ 3.0 cm may not be sufficient in the suboptimal visualization score group. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Abbreviated MRI for Secondary Surveillance of Recurrent Hepatocellular Carcinoma After Presumed Curative Treatment.

BACKGROUND: Little is known about the performance of abbreviated MRI (AMRI) for secondary surveillance of recurrent hepatocellular carcinoma (HCC) after curative treatment. PURPOSE: To evaluate the detection performance of AMRI for secondary surveillance of HCC after curative treatment. STUDY TYPE: Retrospective. POPULATION: A total of 243 patients (183 men and 60 women; median age, 65 years) who underwent secondary surveillance for HCC using gadoxetic acid-enhanced MRI after more than 2 year of disease-free period following curative treatment, including surgical resection or radiofrequency ablation (RFA). FIELD STRENGTH/SEQUENCE: A 3.0 T/noncontrast AMRI (NC-AMRI) (T2-weighted fast spin-echo, T1-weighted gradient echo, and diffusion-weighted images), hepatobiliary phase AMRI (HBP-AMRI) (T2-weighted fast spin-echo, diffusion-weighted, and HBP images), and full-sequence MRI ASSESSMENT: Four board-certified radiologists independently reviewed NC-AMRI, HBP-AMRI, and full-sequence MRI sets of each patient for detecting recurrent HCC. STATISTICAL TESTS: Per-lesion sensitivity, per-patient sensitivity and specificity for HCC detection at each set were compared using generalized estimating equation. RESULTS: A total of 42 recurred HCCs were confirmed in the 39 patients. The per-lesion and per-patient sensitivities did not show significant differences among the three image sets for either reviewer (P ≥ 0.358): per-lesion sensitivity: 59.5%-83.3%, 59.5%-85.7%, and 59.5%-83.3%, and per-patient sensitivity: 53.9%-83.3%, 56.4%-85.7%, and 53.9%-83.3% for NC-AMRI, HBP-AMRI, and full-sequence MRI, respectively. Per-lesion pooled sensitivities of NC-AMRI, HBP-AMRI, and full-sequence MRI were 72.6%, 73.2%, and 73.2%, with difference of -0.6% (95% confidence interval: -6.7, 5.5) between NC-AMRI and full-sequence MRI and 0.0% (-6.1, 6.1) between HBP-AMRI and full-sequence MRI. Per-patient specificity was not significantly different among the three image sets for both reviewers (95.6%-97.1%, 95.6%-97.1%, and 97.6%-98.5% for NC-AMRI and HBP-AMRI, respectively; P ≥ 0.117). DATA CONCLUSION: NC-AMRI and HBP-AMRI showed no significant difference in detection performance to that of full-sequence gadoxetic acid-enhanced MRI during secondary surveillance for HCC after more than 2-year disease free interval following curative treatment. Based on its good detection performance, short scan time, and lack of contrast agent-associated risks, NC-AMRI is a promising option for the secondary surveillance of HCC. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Comparative Performance of 2018 LI-RADS versus Modified LIRADS (mLI-RADS): An Individual Participant Data Meta-Analysis.

BACKGROUND: LI-RADS version 2018 (v2018) is used for non-invasive diagnosis of hepatocellular carcinoma (HCC). A recently proposed modification (known as mLI-RADS) demonstrated improved sensitivity while maintaining specificity and positive predictive value (PPV) of LI-RADS category 5 (definite HCC) for HCC. However, mLI-RADS requires multicenter validation. PURPOSE: To evaluate the performance of v2018 and mLI-RADS for liver lesions in a large, heterogeneous, multi-national cohort of patients at risk for HCC. STUDY TYPE: Systematic review and meta-analysis using individual participant data (IPD) [Study Protocol: https://osf.io/duys4]. POPULATION: 2223 observations from 1817 patients (includes all LI-RADS categories; females = 448, males = 1361, not reported = 8) at elevated risk for developing HCC (based on LI-RADS population criteria) from 12 retrospective studies. FIELD STRENGTH/SEQUENCE: 1.5T and 3T; complete liver MRI with gadoxetate disodium, including axial T2w images and dynamic axial fat-suppressed T1w images precontrast and in the arterial, portal venous, transitional, and hepatobiliary phases. Diffusion-weighted imaging was used when available. ASSESSMENT: Liver observations were categorized using v2018 and mLI-RADS. The diagnostic performance of each system's category 5 (LR-5 and mLR-5) for HCC were compared. STATISTICAL TESTS: The Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS-2 was applied to determine risk of bias and applicability. Diagnostic performances were assessed using the likelihood ratio test for sensitivity and specificity and the Wald test for PPV. The significance level was P < 0.05. RESULTS: 17% (2/12) of the studies were considered low risk of bias (244 liver observations; 164 patients). When compared to v2018, mLR-5 demonstrated higher sensitivity (61.3% vs. 46.5%, P < 0.001), similar PPV (85.3% vs. 86.3%, P = 0.89), and similar specificity (85.8% vs. 90.8%, P = 0.16) for HCC. DATA CONCLUSION: This study confirms mLR-5 has higher sensitivity than LR-5 for HCC identification, while maintaining similar PPV and specificity, validating the mLI-RADS proposal in a heterogeneous, international cohort. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Evaluation and Prognostication of Gd-EOB-DTPA MRI and CT in Patients With Macrotrabecular-Massive Hepatocellular Carcinoma.

BACKGROUND: Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is highly aggressive. Comparing the diagnosis ability of CT and gadoxetate disodium (Gd-EOB-DTPA) MRI for MTM-HCC are lacking. PURPOSE: To compare the performance of Gd-EOB-DTPA MRI and CT for differentiating MTM-HCC from non-MTM-HCC, and determine the prognostic indicator. STUDY TYPE: Retrospective. SUBJECTS: Post-surgery HCC patients, divided into the training (N = 272) and external validation (N = 44) cohorts. FIELD STRENGTH/SEQUENCE: 3.0 T, T1-weighted imaging, in-opp phase, and T1-weighted volumetric interpolated breath-hold examination/liver acquisition with volume acceleration; enhanced CT. ASSESSMENT: Three radiologists evaluated clinical characteristics (sex, age, liver disease, liver function, blood routine, alpha-fetoprotein [AFP] and prothrombin time international normalization ratio [PT-INR]) and imaging features (tumor length, intratumor fat, hemorrhage, arterial phase peritumoral enhancement, intratumor necrosis or ischemia, capsule, and peritumoral hepatobiliary phase [HBP] hypointensity). Compared the performance of CT and MRI for diagnosing MTM-HCC. Follow-up occurred every 3-6 months, and nomogram demonstrated the probability of MTM-HCC. STATISTICAL TESTS: Fisher test, t-test or Wilcoxon rank-sum test, area under the curve (AUC), 95% confidence interval (CI), multivariable logistic regression, Kaplan-Meier curve, and Cox proportional hazards. Significance level: P < 0.05. RESULTS: Gd-EOB-DTPA MRI (AUC: 0.793; 95% CI, 0.740-0.839) outperformed CT (AUC: 0.747; 95% CI, 0.691-0.797) in the training cohort. The nomogram, incorporating AFP, PT-INR, and MRI features (non-intratumor fat, incomplete capsule, intratumor necrosis or ischemia, and peritumoral HBP hypointensity) demonstrated powerful performance for diagnosing MTM-HCC with an AUC of 0.826 (95% CI, 0.631-1.000) in the external validation cohort. Median follow-up was 347 days (interquartile range [IQR], 606 days) for the training cohort and 222 days (IQR, 441 days) for external validation cohort. Intratumor necrosis or ischemia was an independent indicator for poor prognosis. DATA CONCLUSION: Gd-EOB-DTPA MRI might assist in preoperative diagnosis of MTM-HCC, and intratumor necrosis or ischemia was associated with poor prognosis. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Predicting estimated glomerular filtration rate after partial and radical nephrectomy based on split renal function measured by radionuclide: a large-scale retrospective study.

PURPOSE: The purpose of this study was to develop predictive models for postoperative estimated glomerular filtration rate (eGFR) based on the split glomerular filtration rate measured by radionuclide (rGFR), as choosing radical nephrectomy (RN) or partial nephrectomy (PN) for complex renal masses requires accurate prediction of postoperative eGFR. METHODS: Patients who underwent RN or PN for a single renal mass at Xijing Hospital between 2008 and 2022 were retrospectively included. Preoperative split rGFR was evaluated using technetium-99 m-diethylenetriaminepentaacetic acid (Tc-99 m DTPA) renal dynamic imaging, and the postoperative short-term (< 7 days) and long-term (3 months to 5 years) eGFRs were assessed. Linear mixed-effect models were used to predict eGFRs, with marginal R2 reflecting predictive ability. RESULTS: After excluding patients with missing follow-up eGFRs, the data of 2251 (RN: 1286, PN: 965) and 2447 (RN: 1417, PN: 1030) patients were respectively included in the long-term and short-term models. Two models were established to predict long-term eGFRs after RN (marginal R2 = 0.554) and PN (marginal R2 = 0.630), respectively. Two other models were established to predict short-term eGFRs after RN (marginal R2 = 0.692) and PN (marginal R2 = 0.656), respectively. In terms of long-term eGFRs, laparoscopic and robotic surgery were superior to open surgery in both PN and RN. CONCLUSIONS: We developed novel tools for predicting short-term and long-term eGFRs after RN and PN based on split rGFR that can help in preoperative decision-making.

An improved diagnostic algorithm for subcentimeter hepatocellular carcinoma on gadoxetic acid-enhanced MRI.

OBJECTIVES: Accurate diagnosis of subcentimeter hepatocellular carcinoma (HCC) is a challenge also with gadoxetic acid-enhanced MRI (EOB-MRI). This study aimed to assess the diagnostic accuracy of the Liver Imaging Reporting and Data System (LI-RADS) for subcentimeter HCC and to determine whether new diagnostic criteria (washout either on portal venous phase (PVP) or transitional phase (TP)) would improve the diagnostic performance. METHODS: We evaluated 240 subcentimeter observations in 225 consecutive treatment-naïve patients at risk of HCC. Final diagnoses were 132 HCCs (all by pathology) and 108 non-HCC (41 by pathology and 67 by follow-up). Two radiologists assessed MR imaging features and assigned LI-RADS categories. A variety of diagnostic criteria were developed by combining significant MRI features based on washout on PVP or TP. Diagnostic performance was compared. RESULTS: Non-rim arterial phase hyperenhancement (non-rim APHE), washout on PVP or TP, and hepatobiliary-phase hypointensity were significant predictors for subcentimeter HCC diagnosis according to multivariable analysis. One criterion (non-rim APHE and washout on PVP or TP) yielded higher sensitivity (68.2% vs. 56.8%, p = 0.011) with comparable specificity (91.7% vs. 92.6%, p > 0.999) compared to the LR-4 category. This criterion had improved sensitivity (68.2% vs. 49.2%, p < 0.001) and slightly decreased specificity (91.7% vs. 94.4%, p = 0.250) compared to non-rim APHE with washout on PVP. CONCLUSIONS: LI-RADS exhibits modest diagnostic performance for subcentimeter HCC. Our new criterion (non-rim APHE and non-peripheral washout on PVP or TP) may increase the diagnostic sensitivity without compromised specificity compared to the LR-4 category. KEY POINTS: • The LR-4 category shows modest diagnostic performance for the diagnosis of subcentimeter HCC on EOB-MRI with a sensitivity and specificity of 56.8% and 92.6%, respectively. • Non-rim APHE, non-peripheral washout on PVP or TP, and HBP hypointensity were independent predictors for the diagnosis of subcentimeter HCC. • The combination of non-rim APHE and non-peripheral washout on PVP or TP improves the sensitivity from 56.8 to 68.2% (p = 0.011) with comparable specificity (91.7 vs. 92.6%, p > 0.999).

Abbreviated MRI with second shot arterial phase for HCC evaluation: modified version of LI-RADS and recall reduction strategy.

OBJECTIVES: To evaluate the feasibility of simulated abbreviated MRI (AMRI) with second shot arterial phase (SSAP) for HCC surveillance and diagnosis. METHODS: A total of 129 consecutive patients (age, 58.8 ± 11.4 years; male, 71.3%) underwent gadoxetic acid-enhanced MRI using a modified injection protocol for HCC evaluation from July 2017 to February 2018. The modified injection protocol consisted of routine dynamic imaging (6 mL) and SSAP imaging (4 mL). Two radiologists independently reviewed two AMRI sets: AMRI without SSAP (surveillance set) and AMRI with SSAP (diagnosis set). A modified version of the Liver Imaging Reporting and Data System (LI-RADS) for the diagnosis set was devised by referring to contrast-enhanced ultrasound LI-RADS. RESULTS: Sixty-seven patients with HCC and 62 patients without HCC were included. In the surveillance set, sensitivity and specificity for the detection of patients with HCC were 95.5% and 96.8%, and 94.0% and 96.8% in reviewers 1 and 2, respectively. In the diagnosis set, the scores of most HCCs (76/78, 97.4%) were consistent between LI-RADS of full-protocol and modified LI-RADS of AMRI with SSAP protocol. When the HCC surveillance and diagnosis strategy was changed from strategy 1 (AMRI without SSAP) to strategy 2 (AMRI with SSAP), the recall rate significantly decreased from 52.7 to 3.9% (p < 0.001). CONCLUSIONS: The modified LI-RADS score of the AMRI with SSAP protocol showed high agreement with the LI-RADS score of the full protocol. The HCC surveillance and diagnosis strategy using the AMRI with SSAP protocol reduced the recall rate. These results may enable to diagnose HCC simultaneously with surveillance. KEY POINTS: • A modified version of LI-RADS was devised for the diagnostic algorithm using AMRI with the second shot arterial phase (SSAP) by referring to CEUS LI-RADS. • The modified LI-RADS scores using AMRI with SSAP showed a high concordance rate with the conventional LI-RADS score using full-protocol MRI. • The recall rate significantly decreased when the HCC surveillance and diagnosis strategy was changed from strategy 1 (AMRI without SSAP; surveillance then recall test) to strategy 2 (AMRI with SSAP; simultaneous surveillance and diagnosis).

Performance of free-breathing dynamic T1-weighted sequences in patients at risk of developing motion artifacts undergoing gadoxetic acid-enhanced liver MRI.

OBJECTIVES: To evaluate the recall rate and performance of free-breathing T1W dynamic imaging in patients who underwent gadoxetic acid-enhanced liver MRI. METHODS: We retrospectively reviewed patients who underwent free-breathing dynamic T1WI liver MRI using Cartesian (XD-VIBE) or self-gated radial (SG-GRASP) sequences at two institutions. Four radiologists independently reviewed the overall image quality, streak, and motion artifacts for precontrast, arterial, and portal venous phases on a 4-point scale. Hepatic observations were annotated and assessed according to LI-RADS v2018. RESULTS: In total, 360 patients were included (XD-VIBE [n = 253], SG-GRASP [n = 107]). The overall image quality of free-breathing T1WI was 3.4 ± 0.4, 3.2 ± 0.4, and 3.5 ± 0.4 for precontrast, arterial, and portal venous phases, respectively. The actual recall rate was 0.6% (2/360). The SG-GRASP group showed fewer motion artifacts and more streak artifacts than the XD-VIBE group in all phases (p < 0.001 for all). The overall image quality was not significantly different between the two sequences in arterial (3.2 ± 0.4 in both, p = 0.607) and portal venous phases (3.5 ± 0.4 in XD-VIBE, 3.4 ± 0.4 in SG-GRASP, p = 0.214). Two sequences did not show significant differences in the lesion detection rate (figure of merit, FOM: 0.67 vs. 0.68, p = 0.876) or diagnostic performance for hepatocellular carcinoma (FOM: 0.55 vs. 0.62, p = 0.105). CONCLUSIONS: Both XD-VIBE and SG-GRASP provided sufficient image quality for patients at risk of developing motion artifacts, without significant differences in image quality or the lesion detection rate between sequences. KEY POINTS: • The overall image quality of free-breathing T1-weighted images using Cartesian or radial sequences was 3.4 ± 0.4, 3.2 ± 0.4, and 3.5 ± 0.4 for precontrast, arterial, and portal venous phases, respectively. • Only 0.3% (1/360) had undiagnostic exams and the actual recall rate was 0.6% (2/360) in patients who underwent free-breathing dynamic T1WI. • The overall lesion detection rate was 0.67 without a significant difference between Cartesian and radial sequences (figure of merit: 0.67 vs. 0.68, respectively, p = 0.876).

Influence of dilution on arterial-phase artifacts and signal intensity on gadoxetic acid-enhanced liver MRI.

OBJECTIVES: To investigate the effect of saline-diluted gadoxetic acid, done for arterial-phase (AP) artifact reduction, on signal intensity (SI), and hence focal lesion conspicuity on MR imaging. METHODS: We retrospectively examined 112 patients who each had at least two serial gadoxetic acid-enhanced liver MRIs performed at 1 ml/s, first with non-diluted (ND), then with 1:1 saline-diluted (D) contrast. Two blinded readers independently analyzed the artifacts and graded dynamic images using a 5-point scale. The absolute SI of liver parenchyma, focal liver lesions (if present), aorta, and portal vein at the level of the celiac trunk and the SI of the paraspinal muscle were measured in all phases. The signal-to-norm (SINorm) of the vascular structures, hepatic parenchyma and focal lesions, and the contrast-to-norm (CNorm) of focal liver lesions were calculated. RESULTS: AP artifacts were significantly reduced with dilution. Mean absolute contrast-enhanced liver SI was significantly higher on the D exams compared to the ND exams. Likewise, SINorm of liver parenchyma was significantly higher in all contrast-enhanced phases except transitional phase on the D exams. SINorm values in the AP for the aorta and in the PVP for portal vein were significantly higher on the diluted exams. The CNorm was not significantly different between ND and D exams for lesions in any imaging phase. The interclass correlation coefficient was excellent (0.89). CONCLUSION: Gadoxetic acid dilution injected at 1ml/s produces images with significantly fewer AP artifacts but no significant loss in SINorm or CNorm compared to standard non-diluted images. KEY POINTS: • Diluted gadoxetic acid at slow injection (1 ml/s) yielded images with higher SINorm of the liver parenchyma and preserved CNorm for focal liver lesions. • Gadoxetic acid-enhanced MRI injected at 1 ml/s is associated with arterial-phase (AP) artifacts in 31% of exams, which may degrade image quality and limits focal liver lesion detection. • Saline dilution of gadoxetic acid 1:1 combined with a slow injection rate of 1 ml/s significantly reduced AP artifacts from 31 to 9% and non-diagnostic AP artifacts from 16 to 1%.