Prediction of vessels encapsulating tumor clusters pattern and prognosis of hepatocellular carcinoma based on preoperative gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid magnetic resonance imaging.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) is a novel vascular pattern distinct from microvascular invasion that is significantly associated with poor prognosis in patients with hepatocellular carcinoma (HCC). This study aimed to predict the VETC pattern and prognosis of patients with HCC based on preoperative gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI). METHODS: Patients with HCC who underwent surgical resection and preoperative Gd-EOB-DTPA MRI between January 1, 2016 and August 31, 2022 were retrospectively included. The variables associated with VETC were evaluated using logistic regression. A nomogram model was constructed on the basis of independent risk factors. COX regression was used to determine the variables associated with recurrence-free survival (RFS). RESULTS: A total of 98 patients with HCC were retrospectively included. Peritumoral hypointensity on the hepatobiliary phase (HBP) (odd ratio [OR], 2.58; 95% CI, 1.05-6.33; P = .04), tumor-to-liver signal intensity ratio on HBP of ≤0.75 (OR, 27.80; 95% CI, 1.53-502.91; P = .02), and tumor-to-liver apparent diffusion coefficient ratio of ≤1.23 (OR, 4.65; 95% CI, 1.01-21.38; P = .04) were independent predictors of VETC pattern. A nomogram was constructed by combining the aforementioned 3 significant variables. The accuracy, sensitivity, and specificity were 69.79%, 71.74%, and 68.00%, respectively, with an area under the receiver operating characteristic curve of 0.75 (95% CI, 0.65-0.83). The variables significantly associated with RFS of patients with HCC after surgery were Barcelona Clinic Liver Cancer stage (hazard ratio [HR], 2.15; 95% CI, 1.09-4.22; P = .03) and VETC pattern (HR, 2.28; 95% CI, 1.29-4.02; P = .004). CONCLUSION: The preoperative imaging features based on Gd-EOB-DTPA MRI can be used to predict the VETC pattern, which has prognostic significance for postoperative RFS of patients with HCC.

Evaluation of signal intensity changes in dentate nucleus and globus pallidus on magnetic resonance imaging after intrathecal gadolinium-based contrast agent administration.

PURPOSE: Gadolinium deposition has been reported in several normal anatomical structures in the brain after repeated administration of intravenous gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI). This study presents preliminary results to see if there is any gadolinium deposition in the dentate nucleus and globus pallidus after using intrathecal GBCAs. METHODS: Between November 2018 and November 2020, 29 patients who underwent intrathecal contrast-enhanced MR cisternography with the suspicion of rhinorrhea were included in this prospective study. In contrast-enhanced MR cisternography, gadoterate meglumine was administered by intrathecal injection at a dose of 1 ml. One month later, patients had a control MRI with 3D T1 SPACE fat-saturated (FS) and susceptibility weighted images (SWI) sequences. The ratio of dentate nucleus signal intensity to middle cerebellar peduncle signal intensity (DN/MCP ratio) and the ratio of globus pallidus signal intensity to thalamus signal intensity (GP/T ratio) were calculated using region of interest (ROI) on pre-contrast and control MRI sequences. RESULTS: There was no significant difference for DN/MCP ratio and GP/T ratio on 3D T1 SPACE FS and SWI sequences after intrathecal GBCAs administration compared to baseline MRI. CONCLUSION: Administration of intrathecal GBCAs did not cause a measurable change in the signal intensity of the dentate nucleus and globus pallidus after a single injection.

Comparison of the efficacy of the gadoxetic acid MRI-derived relative enhancement index (REI) and functional liver imaging score (FLIS) in predicting liver function: validation with Albumin-Bilirubin (ALBI) grade.

PURPOSE: This study compared the predictive performance of the relative enhancement index (REI) derived from gadoxetic acid (GA)-enhanced MRI with that of the functional liver imaging score (FLIS) in estimating liver function among patients with chronic liver disease (CLD) or liver cirrhosis (LC) by validating them with the albumin-bilirubin (ALBI) grade. MATERIALS AND METHODS: We retrospectively examined 166 patients (79 women, 87 men; 57.4 years) who were diagnosed with LC or CLD and underwent GA-enhanced MRI between August 2020 and September 2023. The enhancement ratio (ER) is calculated using the formula: ER = [hepatobiliary phase liver signal (SI HBP20)-precontrast liver signal (SI pre)]/SI pre. The REI is calculated using the formula: REI = Liver Volume (LV) × ER. FLIS was assigned from the sum of three HBP image features, each scored between 0 and 2: liver parenchymal enhancement, biliary contrast excretion, and portal vein sign. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff values of ER, REI, and FLIS in differentiating between ALBI grades. The area under the curve (AUC), accuracy, sensitivity, and specificity were calculated for REI and FLIS to distinguish the ALBI grades. Spearman's rank correlation was used to evaluate the ER, REI, and FLIS correlations between the ALBI grades. To evaluate inter-reader reliability for LV, ER, REI, and FLIS, intraclass correlation coefficient (ICC) was used. RESULTS: ROC curve analysis showed that the optimal cutoff value of REI for predicting ALBI Grade 1 was 899-905 for readers 1 and 2 and 461-477 for ALBI Grade 3, respectively. REI performed best in predicting ALBI Grade 1, achieving an accuracy range of 94%-92.2%, sensitivity of 94.9%-94.1%, and specificity of 91.7%-87.5% for readers 1 and 2, respectively. All parameters showed high accuracy in distinguishing ALBI Grade 3 from other grades. However, REI outperformed the others, showing an accuracy range of 98.8%-97.6%, sensitivity of 94.4%-94.4%, and specificity of 99.3%-98% for readers 1 and 2, respectively. REI showed the best and very strong correlation with ALBI for both readers. CONCLUSION: REI showed a very strong correlation with the ALBI grades for assessing liver function. It outperformed FLIS in predicting the ALBI grades, indicating its potential as a radiologic tool comparable to or better than FLIS in predicting liver function, especially given its dependence on liver volume.

Comparison of Four Diagnostic Guidelines for Hepatocellular Carcinoma Using Gadoxetic Acid-enhanced Liver MRI.

Background Noninvasive diagnostic guidelines for hepatocellular carcinoma (HCC) vary across different global geographic areas, especially regarding criteria about gadoxetic acid-enhanced MRI. Purpose To compare the diagnostic performance of four different international HCC diagnosis guidelines and readers' judgment in diagnosing HCC using gadoxetic acid-enhanced MRI in patients at high risk for HCC. Materials and Methods This retrospective study included patients who had not undergone treatment, were at risk for HCC, and who underwent gadoxetic acid-enhanced MRI from January 2015 to June 2018 from 11 tertiary hospitals in South Korea. Four radiologists independently reviewed focal liver lesions (FLLs) according to four guidelines: American Association for the Study of Liver Diseases (AASLD)/Liver Imaging Reporting and Data System (LI-RADS), Korean Liver Cancer Association-National Cancer Center (KLCA-NCC), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL). Reader judgment (HCC or not HCC) was also recorded. Malignant FLLs were confirmed at pathology, and histologic and clinical follow-up data were used for benign FLLs. The guidelines' diagnostic performance was compared using generalized estimating equations. Additionally, the diagnostic odds ratio was assessed. Results A total of 2445 FLLs (median size, 27.4 mm) were analyzed in 2237 patients (mean age, 59 years ± 11 [SD]; 1666 male patients); 69.3% (1694 of 2445) were HCCs. KLCA-NCC showed the highest accuracy (80.0%; 95% CI: 78.7, 81.2; P = .001), with high sensitivity in Eastern guidelines (APASL, 89.1% [95% CI: 87.8, 90.3]; KLCA-NCC, 78.2% [95% CI: 76.6, 79.7]) and high specificity in Western guidelines (AASLD/LI-RADS, 89.6% [95% CI: 87.8, 91.2]; EASL, 88.1% [95% CI: 86.2, 89.9]) (P = .001). The diagnostic odds ratios were 20.7 (95% CI: 17.0, 25.3) for AASLD/LI-RADS, 18.9 (95% CI: 15.8, 22.6) for KLCA-NCC, 16.8 (95% CI: 13.8, 20.4) for EASL, and 8.9 (95% CI: 7.4, 10.7) for APASL. The readers' judgment demonstrated higher accuracy than that of the guidelines (accuracy, 86.0%; 95% CI: 84.9, 86.9; P = .001). Conclusion Among four different international HCC diagnosis guidelines, Eastern guidelines demonstrated higher sensitivity, whereas Western guidelines displayed higher specificity. KLCA-NCC achieved the highest accuracy, and AASLD/LI-RADS exhibited the highest diagnostic odds ratio. © RSNA, 2024 Supplemental material is available for this article.

A Bis(Aquated) Mn(II)-Based MRI Contrast Agent with a Rigid Hydroquinazoline Unit: Synthesis, Characterization, and in Vivo MR Imaging Study.

Since the finding of nephrogenic systemic fibrosis (NFS) in patients with renal impairment and the long-term accumulation of Gd(III) ions in the central nervous system, the search for nongadolinium ion-based MRI contrast agents made of nutrient metal ions has drawn paramount attention. In this context, the development of Mn(II)-based MRI contrast agents has been a subject of interest for the last few decades. Herein, we report a pentadentate ligand (Li2[BenzPic2]) composed of two picolinate moieties and a rigid 1,2,3,4-tetrahydroquinazoline unit and the corresponding bis(aquated) Mn(II) complex (Complex 1). The complex exhibited high thermodynamic stability (log Kcond = 11.62) and kinetic inertness similar to that of the clinically approved Gd(III)-based contrast agent Magnevist. Complex 1 exerted longitudinal relaxivity (r1) of 5.32 mM-1 s-1 at 1.41 T, 37 °C, pH 7.4, and it increased by 3.6-fold in the presence of serum albumin protein, confirming a substantial rigidifying interaction (albumin association constant KA = 1.66 × 103 M-1) between the protein and the amphiphilic (log P = -0.45) contrast agent. An intravenous dose of 0.08 mmol/kg in a healthy mouse, excellent MRI signal intensity enhancement in the vasculature of the mouse liver, and brightened images of the gallbladder, kidney, and liver were realized.

MRI-Based Cell Tracking of OATP-Expressing Cell Transplants by Pre-Labeling with Gd-EOB-DTPA.

PURPOSE: A critical step in cell-based therapies is determining the exact position of transplanted cells immediately post-transplant. Here, we devised a method to detect cell transplants immediately post-transplant, using a clinical gadolinium-based contrast agent. These cells were detected as hyperintense signals using a clinically familiar T1-weighted MRI protocol. PROCEDURES: HEK293 cells were stably transduced to express human OATP1B3, a hepatic organic anion transporting polypeptide that transports Gd-EOB-DTPA into cells that express the transporters, the intracellular accumulation of which cells causes signal enhancement on T1-weighted MRI. Cells were pre-labeled prior to injection in media containing Gd-EOB-DTPA for MRI evaluation and indocyanine green for cryofluorescence tomography validation. Labeled cells were injected into chicken hearts, in vitro, after which MRI and cryofluorescence tomography were performed in sequence. RESULTS: OATP1B3-expressing cells had substantially reduced T1 following labeling with Gd-EOB-DTPA in culture. Following their implantation into chicken heart, these cells were robustly identified in T1-weighted MRI, with image-derived injection volumes of cells commensurate with intended injection volumes. Cryofluorescence tomography showed that the areas of signal enhancement in MRI overlapped with areas of indocyanine green signal, indicating that MRI signal enhancement was due to the transplanted cells. CONCLUSIONS: OATP1B3-expressing cells can be pre-labeled with Gd-EOB-DTPA prior to injection into tissue, affording the use of clinically familiar T1-weighted MRI to robustly detect cell transplants immediately after transplant. This procedure is easily generalizable and has potential advantages over the use of iron oxide based cell labeling agents and imaging procedures.

Lipophilic Group-Modified Manganese(II)-Based Contrast Agents for Vascular and Hepatobiliary Magnetic Resonance Imaging.

Effective vascular and hepatic enhancement and better safety are the key drivers for exploring gadolinium-free hepatobiliary contrast agents. Herein, a facile strategy proposes that the high lipophilicity may be favorable to enhancing sequentially vascular and hepatobiliary signal intensity based on the structure-activity relationship that both hepatic uptake and interaction with serum albumins partly depend on lipophilicity. Therefore, 11 newly synthesized derivatives of manganese o-phenylenediamine-N,N,N',N'-tetraacetic acid (MnLs) were evaluated as vascular and hepatobiliary agents. The maximum signal intensities of the heart, liver, and kidneys were strongly correlated with log P, a key indicator of lipophilicity. The most lipophilic agent, MnL6, showed favorable relaxivity when binding with serum albumin, good vascular enhancement, rapid excretion, and reliable hepatobiliary phases comparable to a classic hepatobiliary agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for in vivo liver tumor imaging. Inhibition experiments confirmed the hepatic targeting of MnL6 is mediated by organic anion-transporting polypeptides.

Amorphous Albumin Gadolinium-Based Nanoparticles for Ultrahigh-Resolution Magnetic Resonance Angiography.

Magnetic resonance angiography (MRA) contrast agents are extensively utilized in clinical practice due to their capability of improving the image resolution and sensitivity. However, the clinically approved MRA contrast agents have the disadvantages of a limited acquisition time window and high dose administration for effective imaging. Herein, albumin-coated gadolinium-based nanoparticles (BSA-Gd) were meticulously developed for in vivo ultrahigh-resolution MRA. Compared to Gd-DTPA, BSA-Gd exhibits a significantly higher longitudinal relaxivity (r1 = 76.7 mM-1 s-1), nearly 16-fold greater than that of Gd-DTPA, and an extended blood circulation time (t1/2 = 40 min), enabling a dramatically enhanced high-resolution imaging of microvessels (sub-200 µm) and low dose imaging (about 1/16 that of Gd-DTPA). Furthermore, the clinically significant fine vessels were successfully mapped in large mammals, including a circle of Willis, kidney and liver vascular branches, tumor vessels, and differentiated arteries from veins using dynamic contrast-enhanced MRA BSA-Gd, and have superior imaging capability and biocompatibility, and their clinical applications hold substantial promise.

A dual-targeted Gd-based contrast agent for magnetic resonance imaging in tumor diagnosis.

Enhanced magnetic resonance imaging (MRI) has important clinical value in the diagnosis of tumors. Much effort has been made to improve the relaxivity and specificity of contrast agents (CAs) in tumor diagnosis over the past few decades. However, there is still a lack of CAs which not only enhance the signal intensity of tumors rather than surrounding tissues in MRI but also maintain a high signal intensity prolonged for a long time. Herein, we synthesized a dual-targeted CA, RGD-(DOTA-Gd)-TPP (RDP), in which RGD is used to target the αvß3 integrin receptor overexpressed in tumor cells and TPP is used to bind to a mitochondrion further. The structure of RDP was characterized and its properties, such as relaxivity and biosafety, were measured and in vitro and in vivo MRI assays were carried out. It has been proven that RDP has higher relaxivity of aqueous solution than Magnevist used in clinics. Moreover, RDP achieved higher signal intensity and a longer signal duration in tumor imaging. Therefore, RDP can be applied as the potential dual-targeted MRI CA for clinical tumor diagnosis.

Intra-patient and inter-observer image quality analysis in liver MRI study with gadoxetic acid using two different multi-arterial phase techniques.

PURPOSE: To evaluate intra-patient and interobserver agreement in patients who underwent liver MRI with gadoxetic acid using two different multi-arterial phase (AP) techniques. METHODS: A total of 154 prospectively enrolled patients underwent clinical gadoxetic acid-enhanced liver MRI twice within 12 months, using two different multi-arterial algorithms: CAIPIRINHA-VIBE and TWIST-VIBE. For every patient, breath-holding time, body mass index, sex, age were recorded. The phase without contrast media and the APs were independently evaluated by two radiologists who quantified Gibbs artefacts, noise, respiratory motion artefacts, and general image quality. Presence or absence of Gibbs artefacts and noise was compared by the McNemar's test. Respiratory motion artefacts and image quality scores were compared using Wilcoxon signed rank test. Interobserver agreement was assessed by Cohen kappa statistics. RESULTS: Compared with TWIST-VIBE, CAIPIRINHA-VIBE images had better scores for every parameter except higher noise score. Triple APs were always acquired with TWIST-VIBE but failed in 37% using CAIPIRINHA-VIBE: 11% have only one AP, 26% have two. Breath-holding time was the only parameter that influenced the success of multi-arterial techniques. TWIST-VIBE images had worst score for Gibbs and respiratory motion artefacts but lower noise score. CONCLUSION: CAIPIRINHA-VIBE images were always diagnostic, but with a failure of triple-AP in 37%. TWIST-VIBE was successful in obtaining three APs in all patients. Breath-holding time is the only parameter which can influence the preliminary choice between CAIPIRINHA-VIBE and TWIST-VIBE algorithm. ADVANCES IN KNOWLEDGE: If the patient is expected to perform good breath-holds, TWIST-VIBE is preferable; otherwise, CAIPIRINHA-VIBE is more appropriate.

Noninvasive Diagnosis of Kidney Dysfunction Using a Small-Molecule Manganese-Based Magnetic Resonance Imaging Probe.

Contrast-enhanced magnetic resonance imaging (CE-MRI) is a promising approach for the diagnosis of kidney diseases. However, safety concerns, including nephrogenic systemic fibrosis, limit the administration of gadolinium (Gd)-based contrast agents (GBCAs) in patients who suffer from renal impairment. Meanwhile, nanomaterials meet biosafety concerns because of their long-term retention in the body. Herein, we propose a small-molecule manganese-based imaging probe Mn-PhDTA as an alternative to GBCAs to assess renal insufficiency for the first time. Mn-PhDTA was synthesized via a simple three-step reaction with a total yield of up to 33.6%, and a gram-scale synthesis can be realized. Mn-PhDTA has an r1 relaxivity of 2.72 mM-1 s-1 at 3.0 T and superior kinetic inertness over Gd-DTPA and Mn-EDTA with a dissociation time of 60 min in the presence of excess Zn2+. In vivo and in vitro experiments demonstrate their good stability and biocompatibility. In the unilateral ureteral obstruction rats, Mn-PhDTA provided significant MR signal enhancement, enabled distinguishing structure changes between the normal and damaged kidneys, and evaluated the renal function at different injured stages. Mn-PhDTA could act as a potential MRI contrast agent candidate for the replacement of GBCAs in the early detection of kidney dysfunction and analysis of kidney disease progression.

Liver Biliary Function Evaluation on a 1.5T Magnetic Resonance Imaging Scan by T1 Reduction Rate Assessment Using Variable-Flip-Angle Sequences.

OBJECTIVE: Magnetic resonance (MR) relaxometry is an absolute and reproducible quantitative method, compared with signal intensity for the evaluation of liver biliary function. This is obtainable by the T1 reduction rate (T1RR), as it carries a smaller systematic error than the pre/post contrast agent T1 measurement. We aimed to develop and test an MR T1 relaxometry tool tailored for the evaluation of liver T1RR after gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid administration on 1.5T MR. METHODS: In vitro/vivo (liver) T1RR values with two 3D FLASH variable-flip-angle sequences were calculated by a MATLAB algorithm. In vitro measurements were done by 2 physicists, in consensus. The prospective in vivo study was approved by the local ethical committee and performed on 13 normal/26 cirrhotic livers. A supplemental test in 5 normal/5 cirrhotic livers, out of the studied series, was done to compare the results of our method (without B1 inhomogeneity correction) and those of a standardized commercial tool (with B1 inhomogeneity correction). All in vivo evaluations were performed by 2 radiologists with 7 years of experience in abdominal imaging. Open-source Java-based software ImageJ was used to draw the free-hand regions of interest on liver section and for the measurement of hepatic T1RR values. The T1RR values of each group of patients were compared to assess statistically significant differences. All statistical analyses were performed with IBM-SPSS Statistics. In vivo evaluations, the intrareader and interreader reliability was assessed by intraclass correlation coefficient. RESULTS: Our method showed good accuracy in evaluating in vitro T1RR with a maximum percentage error of 9% (constant at various time points) with T1 values in the 200- to 1400-millisecond range. In vivo, a high concordance between the T1RR evaluated with the proposed method and that calculated from the standardized commercial software was verified ( P < 0.05). The median T1RRs were 74.8, 67.9, and 52.1 for the normal liver, Child-Pugh A, and Child-Pugh B cirrhotic groups, respectively. A very good agreement was found, both within intrareader and interreader reliability, with intraclass correlation coefficient values ranging from 0.88 to 0.95 and from 0.85 to 0.90, respectively. CONCLUSIONS: The proposed method allowed accurate reliable in vitro/vivo T1RR assessment evaluation of the liver biliary function after gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid administration.

Multiparametric assessment of microvascular invasion in hepatocellular carcinoma using gadoxetic acid-enhanced MRI.

PURPOSE: To elucidate how precisely microvascular invasion (MVI) in hepatocellular carcinoma (HCC) can be predicted using multiparametric assessment of gadoxetic acid-enhanced MRI. METHODS: In this retrospective single-center study, patients who underwent liver resection or transplantation of HCC were evaluated. Data obtained in patients who underwent liver resection were used as the training set. Nine kinds of MR findings for predicting MVI were compared between HCCs with and without MVI by univariate analysis, followed by multiple logistic regression analysis. Using significant findings, a predictive formula for diagnosing MVI was obtained. The diagnostic performance of the formula was investigated in patients who underwent liver resection (validation set 1) and in patients who underwent liver transplantation (validation set 2) using a receiver operating characteristic curve analysis. The area under the curves (AUCs) of these three groups were compared. RESULTS: A total of 345 patients with 356 HCCs were selected for analysis. Tumor diameter (D) (P = 0.021), tumor washout (TW) (P < 0.01), and peritumoral hypointensity in the hepatobiliary phase (PHH) (P < 0.01) were significantly associated with MVI after multivariate analysis. The AUCs for predicting MVI of the predictive formula were as follows: training set, 0.88 (95% confidence interval (CI) 0.82,0.93); validation set 1, 0.81 (95% CI 0.73,0.87); validation set 2, 0.67 (95% CI 0.51,0.80). The AUCs were not significantly different among three groups (training set vs validation set 1; P = 0.15, training set vs validation set 2; P = 0.09, validation set 1 vs validation set 2; P = 0.29, respectively). CONCLUSION: Our multiparametric assessment of gadoxetic acid-enhanced MRI performed quite precisely and with good reproducibility for predicting MVI.

Assessing regional hepatic function changes after hypertrophy induction by radioembolisation: comparison of gadoxetic acid-enhanced MRI and 99mTc-mebrofenin hepatobiliary scintigraphy.

BACKGROUND: To compare Gd-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and 99mTc-labelled mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests after unilateral radioembolisation (RE) in patients with primary or secondary liver malignancies. METHODS: Twenty-three patients with primary or secondary liver malignancies who underwent Gd-EOB-DTPA-enhanced MRI within a prospective study (REVoluTion) were evaluated. REVoluTion was a prospective open-label, non-randomised, therapy-optimising study of patients undergoing right-sided or sequential RE for contralateral liver hypertrophy at a single centre in Germany. MRI and hepatobiliary scintigraphy were performed before RE (baseline) and 6 weeks after (follow-up). This exploratory subanalysis compared liver enhancement on hepatobiliary phase MRI normalised to the spleen (liver-to-spleen ratio (LSR)) and the muscle (liver-to-muscle ratio (LMR)) with mebrofenin uptake on HBS for the total liver (TL) and separately for the right (RLL) and left liver lobe (LLL). RESULTS: Mebrofenin uptake at baseline and follow-up each correlated significantly with LSR and LMR on MRI for TL (≤ 0.013) and RLL (≤ 0.049). Regarding the LLL, mebrofenin uptake correlated significantly with LMR (baseline, p = 0.013; follow-up, p = 0.004), whereas with LSR, a borderline significant correlation was only seen at follow-up (p = 0.051; p = 0.046). CONCLUSION: LSRs and LMR correlate with mebrofenin uptake in HBS. This study indicates that Gd-EOB-DTPA-enhanced MRI and 99mTc-labelled mebrofenin HBS may equally be used to assess an increase in contralateral liver lobe function after right-sided RE. RELEVANCE STATEMENT: MRI may be a convenient and reliable method for assessing the future liver remnant facilitating treatment planning and monitoring of patients after RE-induced hypertrophy induction. KEY POINTS: • Both MRI and HBS can assess liver function after RE. • Liver enhancement on MRI correlates with mebrofenin uptake on HBS. • MRI might be a convenient alternative for estimating future liver remnants after hypertrophy induction.

A gadoxetic acid-enhanced MRI-based model using LI-RADS v2018 features for preoperatively predicting Ki-67 expression in hepatocellular carcinoma.

PURPOSE: To construct a gadoxetic acid-enhanced MRI (EOB-MRI) -based multivariable model to predict Ki-67 expression levels in hepatocellular carcinoma (HCC) using LI-RADS v2018 imaging features. METHODS: A total of 121 patients with HCC who underwent EOB-MRI were enrolled in this study. The patients were divided into three groups according to Ki-67 cut-offs: Ki-67 ≥ 20% (n = 86) vs. Ki-67 < 20% (n = 35); Ki-67 ≥ 30% (n = 73) vs. Ki-67 < 30% (n = 48); Ki-67 ≥ 50% (n = 45) vs. Ki-67 < 50% (n = 76). MRI features were analyzed to be associated with high Ki-67 expression using logistic regression to construct multivariable models. The performance characteristic of the models for the prediction of high Ki-67 expression was assessed using receiver operating characteristic curves. RESULTS: The presence of mosaic architecture (p = 0.045), the presence of infiltrative appearance (p = 0.039), and the absence of targetoid hepatobiliary phase (HBP, p = 0.035) were independent differential factors for the prediction of high Ki-67 status (≥ 50% vs. < 50%) in HCC patients, while no features could predict high Ki-67 status with thresholds of 20% (≥ 20% vs. < 20%) and 30% (≥ 30% vs. < 30%) (p > 0.05). Four models were constructed including model A (mosaic architecture and infiltrated appearance), model B (mosaic architecture and targetoid HBP), model C (infiltrated appearance and targetoid HBP), and model D (mosaic architecture, infiltrated appearance and targetoid HBP). The model D yielded better diagnostic performance than the model C (0.776 vs. 0.669, p = 0.002), but a comparable AUC than model A (0.776 vs. 0.781, p = 0.855) and model B (0.776 vs. 0.746, p = 0.076). CONCLUSIONS: Mosaic architecture, infiltrated appearance and targetoid HBP were sensitive imaging features for predicting Ki-67 index ≥ 50% and EOB-MRI model based on LI-RADS v2018 features may be an effective imaging approach for the risk stratification of patients with HCC before surgery.

Evaluation and Prediction of Post-Hepatectomy Liver Failure Using Imaging Techniques: Value of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging.

Despite improvements in operative techniques and perioperative care, post-hepatectomy liver failure (PHLF) remains the most serious cause of morbidity and mortality after surgery, and several risk factors have been identified to predict PHLF. Although volumetric assessment using imaging contributes to surgical simulation by estimating the function of future liver remnants in predicting PHLF, liver function is assumed to be homogeneous throughout the liver. The combination of volumetric and functional analyses may be more useful for an accurate evaluation of liver function and prediction of PHLF than only volumetric analysis. Gadoxetic acid is a hepatocyte-specific magnetic resonance (MR) contrast agent that is taken up by hepatocytes via the OATP1 transporter after intravenous administration. Gadoxetic acid-enhanced MR imaging (MRI) offers information regarding both global and regional functions, leading to a more precise evaluation even in cases with heterogeneous liver function. Various indices, including signal intensity-based methods and MR relaxometry, have been proposed for the estimation of liver function and prediction of PHLF using gadoxetic acid-enhanced MRI. Recent developments in MR techniques, including high-resolution hepatobiliary phase images using deep learning image reconstruction and whole-liver T1 map acquisition, have enabled a more detailed and accurate estimation of liver function in gadoxetic acid-enhanced MRI.

Gadolinium Presence in Rat Skin: Assessment of Histopathologic Changes Associated with Small Fiber Neuropathy.

Background The presence of gadolinium traces in the skin after administration of gadolinium-based contrast agents (GBCAs) raised safety concerns regarding a potential association with small fiber neuropathy (SFN). Purpose To investigate signs of SFN in rat foot pads by quantification of the intraepidermal nerve fiber density (IENFD) after multiple GBCA administrations and to evaluate gadolinium concentration, chemical species, and clearance. Materials and Methods Fifty rats received eight intravenous injections of either gadodiamide, gadobutrol, gadoterate, gadoteridol (8 × 0.6 mmol per kilogram of body weight), or saline (1.2 mL per kilogram of body weight), within 2 weeks and were sacrificed 5 days or 5 weeks after the last injection. IENFD was determined with protein gene product (PGP) 9.5 immunofluorescent staining and blinded and automated image analysis. The gadolinium and GBCA concentrations were measured with inductively coupled plasma mass spectrometry (ICP-MS), laser ablation ICP-MS, and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI). P values were calculated using linear contrasts of model analysis. Results The IENFD (measured as geometric mean [SD] and in number of nerve fibers per millimeter of epidermis) was not significantly altered after 5 days (saline, 8.4 [1.1]; gadobutrol, 9.7 [1.2]; gadoterate, 9.2 [1.2]; gadoteridol, 9.9 [1.3]; gadodiamide, 10.5 [1.2]) or 5 weeks (saline, 19.7 [1.4]; gadobutrol, 16.4 [1.6]; gadoterate, 14.3 [1.6]; gadoteridol, 22.2 [1.8]; gadodiamide, 17.9 [1.4]). Gadolinium skin concentrations were highest for gadodiamide after 5 days (16.0 nmol/g [1.1]) and 5 weeks (10.6 nmol/g [1.2], -33%). Macrocyclic agents were lower at 5 days (gadoteridol, 2.6 nmol/g [1.2]; gadobutrol, 2.7 nmol/g [1.1]; and gadoterate, 2.3 nmol/g [1.2]) and efficiently cleared after 5 weeks (gadoteridol, -95%; gadobutrol and gadoterate, -96%). The distribution of gadolinium and IENF did not visually overlap. For macrocyclic agents, gadolinium was found in sweat glands and confirmed to be intact chelate. Conclusion There were no signs of SFN in rat foot pads using multiple dosing regimens at two time points after administration of GBCAs. Macrocyclic GBCAs exhibited lower levels of gadolinium in the skin and were effectively eliminated within 5 weeks compared with linear gadodiamide, and intact macrocyclic GBCA was detected in sweat glands. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Clement in this issue.

Effect of magnetic resonance imaging in liver metastases.

This letter to the editor is a commentary on a study titled "Liver metastases: The role of magnetic resonance imaging." Exploring a noninvasive imaging evaluation system for the biological behavior of hepatocellular carcinoma (HCC) is the key to achieving precise diagnosis and treatment and improving prognosis. This review summarizes the role of magnetic resonance imaging in the detection and evaluation of liver metastases, describes its main imaging features, and focuses on the added value of the latest imaging tools (such as T1 weighted in phase imaging, T1 weighted out of phase imaging; diffusion-weighted imaging, T2 weighted imaging). In this study, I investigated the necessity and benefits of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid for HCC diagnostic testing and prognostic evaluation.

Comparison of 68Ga-DOTATATE Positron Emmited Tomography/Computed Tomography and Gadoxetic Acid-Enhanced Magnetic Resonance Imaging for the Detection of Liver Metastases from Well-Differentiated Neuroendocrine Tumors.

This study aimed to compare the detection of neuroendocrine tumor liver metastases (NLMs) in hepatobiliary-specific contrast-enhanced MRI (pMR) versus 68Ga-DOTATATE PET/CT (DT-PET). This retrospective study cohort included 30 patients with well-differentiated neuroendocrine tumors who underwent both DT-PET and pMR. Two readers independently assessed NLMs count, SUVmax on DT-PET, and signal characteristics on pMR. A consensus review by two additional readers resolved discrepancies between the modalities. Results showed concordance between DT-PET and pMR NLM count in 14/30 patients (47%). pMR identified more NLMs in 12/30 patients (40%), of which 4 patients showed multiple deposits on pMR but only 0-1 lesions on DT-PET. DT-PET detected more in 4/30 patients (13%). Overall, pMR detected more metastases than DT-PET (p = 0.01). Excluding the four outliers, there was excellent agreement between the two methods (ICC: 0.945, 95%CI: 0.930, 0.958). Notably, pMR had a higher NLM detection rate than DT-PET, with correlations found between lesion size on pMR and DT-PET detectability, as well as diffusion restriction on pMR and SUVmax on DT-PET. In conclusion, in consecutive patients with well-differentiated NETs, the detection rate of NLM is higher with pMR than with DT-PET. However, when excluding patients whose tumors do not overexpress somatostatin receptors (13% of the cohort), high concordance in the detection of NLM is observed between DT PET and pMR.

Diagnostic performance of MRI for residual or recurrent hepatocellular carcinoma after locoregional treatment according to contrast agent type: a systematic review and meta­analysis.

PURPOSE: The ideal contrast agent for imaging patients with hepatocellular carcinoma (HCC) following locoregional therapies (LRT) remains uncertain. We conducted a meta-analysis to assess the diagnostic performance of magnetic resonance imaging with extracellular contrast agent (ECA-MRI) and hepatobiliary agent (EOB-MRI) in detecting residual or recurrence HCC following LRT. METHODS: Original studies comparing the diagnostic performance of ECA-MRI and EOB-MRI were systematically identified through comprehensive searches in PubMed, EMBASE, Cochrane Library and Web of Science databases. The pooled sensitivity and specificity of ECA-MRI and EOB-MRI were calculated using a bivariate-random-effects model. Subgroup-analyses were conducted to compare the diagnostic performance of ECA-MRI and EOB-MRI according to different variables. Meta-regression analysis was employed to explore potential sources of study heterogeneity. RESULTS: A total of 15 eligible studies encompassing 803 patients and 1018 lesions were included. Comparative analysis revealed no significant difference between ECA-MRI and EOB-MRI in the overall pooled sensitivity (87% vs. 79%) and specificity (92% vs. 96%) for the detection of residual or recurrent HCC after LRT (P = 0.41), with comparable areas under the HSROC of 0.95 and 0.92. Subgroup analyses indicated no significant diagnostic performance differences between ECA-MRI and EOB-MRI according to study design, type of LRT, most common etiology of liver disease, baseline lesion size, time of post-treated examination and MRI field strength (All P > 0.05). CONCLUSION: ECA-MRI exhibited overall comparable diagnostic performance to EOB-MRI in assessing residual or recurrent HCC after LRT.