Extracellular Contrast Agent Research Articles

Gd-EOB-DTPA-enhanced MRI proves advantageous in selecting surgical candidates for patients with early-stage hepatocellular carcinoma: An analysis in terms of oncological outcomes

Background and aimsTo determine the value of preoperative Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) in comparison with extracellular contrast agent MRI and CT in the selection of surgical candidates among patients with hepatocellular carcinoma (HCC), particularly in terms of oncological outcomes after hepatectomy. MethodsThis retrospective study included 542 consecutive patients who underwent radical hepatectomy for HCC. One group underwent preoperative Gd-EOB-DTPA-enhanced MRI, one group underwent contrast-enhanced CT, and one group underwent extracellular contrast agent MRI. We compared oncologic outcomes including recurrence free survival and overall survival between the three groups. Subgroup analyses were also performed to provide more specific candidates or beneficiaries for preoperative EOB-MRI. ResultsA total of 244 patients had tumor recurrence, with 55 in the EOB-MRI group, 106 in the Routine-MRI group, and 83 in the CT group (p = 0.010). The numbers with early recurrence (<2 years) in each group were 40 (27.03%), 78 (35.78%), and 62 (35.22%), respectively (p = 0.018). The 1, 2, and 3-year recurrence-free survival (RFS) percentages were 82.4%, 73.0%, and 68.2% in the EOB-MRI group, 70.2%, 64.3%, and 56.9% in the Routine-MRI group, and 76.8%, 64.83%, and 58.9% in the CT group (p = 0.010). The 1, 2, and 3-year overall survival percentages were 89.19%, 83.11%, and 80.41% in the EOB-MRI group, 79.82%, 73.86%, and 67.44% in the Routine-MRI group, and 86.55%, 76.14%, and 69.32% in the CT group (p = 0.016). Subgroup analysis showed significant differences in RFS in patients with solitary tumor <3 cm. ConclusionPreoperative EOB-MRI is superior to contrast-enhanced CT or extracellular contrast agent MRI for selecting surgical candidates at low risk of recurrence following hepatic resection for HCC.

Intraindividual comparison of prognostic imaging features of HCCs between MRIs with extracellular and hepatobiliary contrast agents.

Accumulating evidence suggests that certain imaging features of hepatocellular carcinoma (HCC) may have prognostic implications. This study aimed to intraindividually compare MRIs with extracellular contrast agent (ECA-MRI) and hepatobiliary agent (HBA-MRI) for prognostic imaging features of HCC and to compare the prediction of microvascular invasion (MVI) and early recurrence between the two MRIs. The present study included 102 prospectively enrolled at-risk patients (median age, 61.0 years; 83 men) with surgically resected single HCC with both preoperative ECA-MRI and HBA-MRI between July 2019 and June 2023. The McNemar test was used to compare each prognostic imaging feature between the two MRIs. Significant imaging features associated with MVI were identified by multivariable logistic regression analysis, and early recurrence rates (<2 years) were compared between the two MRIs. The frequencies of prognostic imaging features were not significantly different between the two MRIs (p = .07 to >.99). Non-smooth tumour margin (ECA-MRI, odds ratio [OR] = 5.30; HBA-MRI, OR = 7.07) and peritumoral arterial phase hyperenhancement (ECA-MRI, OR = 4.26; HBA-MRI, OR = 4.43) were independent factors significantly associated with MVI on both MRIs. Two-trait predictor of venous invasion (presence of internal arteries and absence of hypoattenuating halo) on ECA-MRI (OR = 11.24) and peritumoral HBP hypointensity on HBA-MRI (OR = 20.42) were other predictors of MVI. Early recurrence rates of any two or more significant imaging features (49.8% on ECA-MRI vs 51.3% on HBA-MRI, p = .75) were not significantly different between the two MRIs. Prognostic imaging features of HCC may be comparable between ECA-MRI and HBA-MRI.

Intraindividual comparison of CT and MRI for predicting vessels encapsulating tumor clusters in hepatocellular carcinoma.

To establish and validate scoring models for predicting vessels encapsulating tumor clusters (VETC) in hepatocellular carcinoma (HCC) using computed tomography (CT) and magnetic resonance imaging (MRI), and to intra-individually compare the predictive performance between the two modalities. We retrospectively included 324 patients with surgically confirmed HCC who underwent preoperative dynamic CT and MRI with extracellular contrast agent between June 2019 and August 2020. These patients were then divided into a discovery cohort (n = 227) and a validation cohort (n = 97). Imaging features and Liver Imaging Reporting and Data System (LI-RADS) categories of VETC-positive HCCs were evaluated. Logistic regression analyses were conducted on the discovery cohort to identify clinical and imaging predictors associated with VETC-positive cases. Subsequently, separate CT-based and MRI-based scoring models were developed, and their diagnostic performance was compared using generalized estimating equations. On both CT and MRI, VETC-positive HCCs exhibited a higher frequency of size > 5.0 cm, necrosis or severe ischemia, non-smooth tumor margin, targetoid appearance, intratumor artery, and heterogeneous enhancement with septations or irregular ring-like structure compared to VETC-negative HCCs (all p < 0.05). Regarding LI-RADS categories, VETC-positive HCCs were more frequently categorized as LR-M than VETC-negative cases (all p < 0.05). In the validation cohort, the CT-based model showed similar sensitivity (76.7% vs. 86.7%, p = 0.375), specificity (83.6% vs. 74.6%, p = 0.180), and area under the curve value (0.80 vs. 0.81, p = 0.910) to the MRI-based model in predicting VETC-positive HCCs. Preoperative CT and MRI demonstrated comparable performance in the identification of VETC-positive HCCs, thus displaying promising predictive capabilities. Both computed tomography and magnetic resonance imaging demonstrated promise in preoperatively identifying the vessel-encapsulating tumor cluster pattern in hepatocellular carcinoma, with no statistically significant difference between the two modalities, potentially adding additional prognostic value. Computed tomography (CT) and magnetic resonance imaging (MRI) show promise in the preoperative identification of vessels encapsulating tumor clusters-positive hepatocellular carcinoma (HCC). HCC with vessels encapsulating tumor cluster patterns were more frequently LR-M compared to those without. These CT and MRI models showed comparable ability in identifying vessels encapsulating tumor clusters-positive HCC.

Safety of Gadoxetate Disodium for Hepatobiliary MRI in Children and Adolescents.

Background Despite a proven role in the characterization of liver lesions, use of the gadolinium-based contrast agent (GBCA) gadoxetate disodium at MRI is limited in children due to a lack of comparative safety data. Purpose To evaluate the safety of the GBCA gadoxetate disodium (a linear ionic hepatobiliary contrast agent [HBA]) in children and adolescents, compared with extracellular contrast agents (ECA). Materials and Methods A retrospective analysis was conducted in children and adolescents aged 18 years or younger who underwent HBA-enhanced MRI at one of three tertiary hospitals from January 2010 to December 2022. The incidence of GBCA-associated acute adverse events was compared between MRI examinations with a HBA and those with ECA. Severity was categorized according to American College of Radiology guidelines (mild, moderate, or severe). (a) Propensity score matching using multivariable logistic regression models and (b) inverse probability of treatment weighting analysis based on nine covariates (age, sex, asthma, allergic rhinitis, chronic urticaria or atopy, food allergy, drug allergy, premedication, and history of GBCA-associated adverse events) were used for confounder adjustment. Results A total of 1629 MRI examinations (ECA, n = 1256; HBA, n = 373) in 1079 patients were included (mean age, 8.6 years ± 6.5; 566 girls). The per-examination incidence of GBCA-associated acute adverse events showed no evidence of a difference, with rates of 0.9% (11 of 1256 examinations) for ECA and 1.3% (five of 373 examinations) for HBA (odds ratio [OR], 1.55 [95% CI: 0.54, 4.46]; P = .42). Acute adverse events were all mild with ECA, whereas with HBA, they were mild for four patients and moderate for one patient. There was no evidence of a difference in the incidence of acute adverse events, even in propensity score matching (OR, 1.33 [95% CI: 0.30, 5.96]; P = .71) and inverse probability of treatment weighting analysis (OR, 0.84 [95% CI: 0.25, 2.86]; P = .78). Conclusion Gadoxetate disodium showed no difference in acute adverse events compared with ECA in children and adolescents, with further large-scale pediatric studies required to confirm its safety. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Otero in this issue.

Rigid Fe(III) Chelate with Phosphonate Pendants: A Stable and Effective Extracellular MRI Contrast Agent.

A novel Fe(III) complex, Fe-tBPCDTA, was synthesized and explored as a potential contrast agent for MRI. Compared to established agents like Fe-EDTA and Fe-tCDTA, Fe-tBPCDTA exhibited moderate relaxivity (r1 = 1.17 s-1·mmol-1) due to its enhanced second-sphere mechanism. It also displayed improved kinetic inertness, lower cytotoxicity, and enhanced redox stability. In vivo studies demonstrated its function as an extracellular fluid agent, providing tumor contrast comparable to that of Gd-DTPA at a higher dosage. Complete renal clearance occurred within 24 h. These findings suggest Fe-tBPCDTA as a promising candidate for further development as a safe and effective extracellular MRI contrast agent.

Pharmacokinetics, safety, and tolerability of the novel tetrameric gadolinium-based MRI contrast agent gadoquatrane in healthy Chinese and Japanese men: Two randomized dose-escalation studies including concentration–QTc modeling

PurposeTo investigate the pharmacokinetics, safety, and tolerability of the novel tetrameric high-relaxivity gadolinium-based contrast agent gadoquatrane in Japanese (Study 1) and Chinese men (Study 2). Participants and methodsIn two similarly designed single-center, randomized, single-blind, placebo-controlled, consecutive-cohort dose-escalation studies, healthy volunteers were randomly assigned to intravenous administration of gadoquatrane (0.01–0.1 mmol gadolinium/kg body weight) or placebo. Study procedures included blood sampling and collection of urine for pharmacokinetic analyses and safety assessments. ResultsTwenty-five healthy Japanese men (mean age ± standard deviation: 26±5.9 years) and 23 healthy Chinese men (31±7.6 years old) were evaluated. In both studies, the pharmacokinetic profile of gadoquatrane was characterized by rapid distribution of the drug into the extracellular space and fast renal elimination. Postdose gadolinium concentrations rapidly declined with a geometric mean effective half-life of 1.3–1.4 h. The exposure increased approximately dose-proportionally with dose. The body weight-normalized volume of distribution was constant across dose levels (0.21–0.24 L/kg). Total recovery of gadolinium in urine amounted to 82–95 % (Study 1) and 96–99 % (Study 2) of the dose administered.Only a few mild, transient adverse events were reported, none of which gave rise to any safety concerns. Exploratory drug concentration–QTc modeling indicated no risk of a clinically relevant QT/QTc prolongation at the anticipated diagnostic dose. ConclusionGadoquatrane was safe and well tolerated at all doses tested. The pharmacokinetic profile was essentially the same as that of other extracellular macrocyclic gadolinium-based contrast agents and was consequentially also similar for Japanese and Chinese participants.

Late/delayed gadolinium enhancement in MRI after intravenous administration of extracellular gadolinium-based contrast agents: is it worth waiting?

The acquisition of images minutes or even hours after intravenous extracellular gadolinium-based contrast agents (GBCA) administration ("Late/Delayed Gadolinium Enhancement" imaging; in this review, further termed LGE) has gained significant prominence in recent years in magnetic resonance imaging. The major limitation of LGE is the long examination time; thus, it becomes necessary to understand when it is worth waiting time after the intravenous injection of GBCA and which additional information comes from LGE. LGE can potentially be applied to various anatomical sites, such as heart, arterial vessels, lung, brain, abdomen, breast, and the musculoskeletal system, with different pathophysiological mechanisms. One of the most popular clinical applications of LGE regards the assessment of myocardial tissue thanks to its ability to highlight areas of acute myocardial damage and fibrotic tissues. Other frequently applied clinical contexts involve the study of the urinary tract with magnetic resonance urography and identifying pathological abdominal processes characterized by high fibrous stroma, such as biliary tract tumors, autoimmune pancreatitis, or intestinal fibrosis in Crohn's disease. One of the current areas of heightened research interest revolves around the possibility of non-invasively studying the dynamics of neurofluids in the brain (the glymphatic system), the disruption of which could underlie many neurological disorders.

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

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. 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. 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). ECA-MRI exhibited overall comparable diagnostic performance to EOB-MRI in assessing residual or recurrent HCC after LRT.

A Magnetic Resonance Imaging-Chemical Exchange Saturation Transfer (MRI-CEST) Method for the Detection of Water Cycling across Cellular Membranes.

Water cycling across the membrane transporters is considered a hallmark of cellular metabolism and it could be of high diagnostic relevance in the characterization of tumors and other diseases. The method relies on the response of intracellular proton exchanging molecules to the presence of extracellular Gd-based contrast agents (GBCAs). Paramagnetic GBCAs enhances the relaxation rate of water molecules in the extracellular compartment and, through membrane exchange, the relaxation enhancement is transferred to intracellular molecules. The effect is detected at the MRI-CEST (Magnetic Resonance Imaging - Chemical Exchange Saturation Transfer) signal of intracellular proton exchanging molecules. The magnitude of the change in the CEST response reports on water cycling across the membrane. The method has been tested on Red Blood Cells and on orthotopic murine models of breast cancer with different degree of malignancy (4T1, TS/A and 168FARN). The distribution of voxels reporting on membrane permeability fits well with the cells' aggressiveness and acts as an early reporter to monitor therapeutic treatments.

Application of liver-specific contrast agents for evaluation of focal liver lesions - Expert recommendations from the Gastrointestinal and Abdominal Imaging Workgroup of the German Roentgen Society.

Contrast-enhanced MRI is the imaging modality of choice for the detection and differential diagnosis of focal liver lesions. Liver-specific contrast agents (CAs) are now well established in addition to extracellular contrast agents. However, there is a lack of explicit recommendations reflecting the pros and cons of each specific contrast agent in the daily routine. Development of recommendations for the clinical application of liver-specific CAs by members of the Gastrointestinal and Abdominal Imaging Workgroup within the Germany Radiological Society, using methodology comparable to that of an S1 guideline with informal consensus. The diagnostic criteria for the evaluation of liver lesions are intentionally outside the scope of this article, as there are already plenty of excellent publications available. The application of liver-specific CAs in the daily routine is associated with advantages and disadvantages due to the specific pharmacokinetic and pharmacodynamic properties and necessitates adjustment of the imaging technique as well consideration during image interpretation. Recommendations for the application of liver-specific CAs are presented based on different clinical scenarios, taking into account current evidence and guidelines. · Both liver-specific and extracellular contrast agents are established. · Liver-specific contrast agents make it possible to draw conclusions about the hepatocellular function of a lesion. · Recommendations for the use of liver-specific contrast agents in the daily routine are presented. · Ringe KI, Fischbach F, Grenacher L et al. Einsatz leberspezifischer Kontrastmittel in der MRT zur Beurteilung von Leberläsionen - Expertenempfehlungen der AG Gastrointestinal- und Abdominaldiagnostik der Deutschen Röntgengesellschaft. Fortschr Röntgenstr 2023; DOI: 10.1055/a-2192-9921.

Estimation of Renal Clearance in Hypertensive Rats According to fMRI Data.

Renal clearance in Wistar rats with multifactorial cardiovasorenal model of arterial hypertension was assessed by fMRI using (EPI_Diffusion_map) protocol after injection of extracellular contrast agent gadolinium Gd-DTPA. Linear regression analysis was used to assess local concentrations of the contrast agent in the abdominal aorta, kidney compartments, pelvis, and bladder areas. Detection of marker clearance in order to verify the glomerular filtration rate was performed by the RPP (Rutland-Patlak plot) method. In 3 months after hypertension modeling, glomerular filtration rate decreased by 2 times in comparison with the control (31.2±0.44 and 62.3±1.31 μl/min/100 g, respectively; p<0.001). Our findings can indicate the formation of hypertensive nephroangiosclerosis in rats with experimental arterial hypertension. It was found that kidney damage in hypertensive rats is associated with hypofiltration.

Guide to use of ferumoxytol for hepatic vascular assessment as part of dual contrast MRI.

Magnetic resonance imaging (MRI) assessment of hepatic vasculature can be challenging in the setting of liver disease and liver lesions. The widely used hepatobiliary contrast agent gadoxetate is an extracellular contrast agent that provides excellent soft tissue characterization but has limitations as a vascular contrast agent. Ferumoxytol is an iron oxide nanoparticle with superparamagnetic properties that can be used as blood pool contrast agent to provide dedicated vascular assessment. We provide a detailed protocol for evaluation of pediatric liver vasculature using ferumoxytol, after imaging of the parenchyma with gadoxetate. We provide multiple examples and discuss practical considerations when incorporating ferumoxytol into practice.

Apparent Variation in Measurement Size of Colorectal Cancer Metastases to the Liver on Dual Contrast MRI.

The aim of this study was to formally investigate the apparent variation in lesion size of hepatic metastatic lesions from colorectal cancer on hepatobiliary phase (HBP) and dual contrast images of magnetic resonance imaging performed with both hepatobiliary and extracellular contrast agents. Patients with known colorectal carcinoma who had undergone dual contrast liver magnetic resonance imaging were identified in our institutional database. Metastatic lesions were measured semiautomatically on both HBP and dual contrast images with a custom software tool that automatically identifies the lesion edge and thereby the lesion diameter. Lesion measurements from both sets of images were compared with a Student t test and Bland-Altman analysis. Lesions were also measured on both HBP and dual contrast images by 2 fellowship-trained abdominal radiologists. Measurements from the software and radiologists were compared with a Student t test and Bland-Altman analysis; interreader agreement was evaluated with the intraclass correlation coefficient. A total of 70 liver lesions in 39 patients was identified. Software-based measurements were significantly larger on HBP than dual contrast images ( P < 0.001), with a mean lesion size of 10.9 ± 4.2 mm for HBP and 10.5 ± 4.2 mm for dual contrast measurements. Radiologist-based measurements showed a similar trend, with HBP measurements being significantly larger than dual contrast measurements ( P < 0.001). Bland-Altman analysis indicated a mean bias ± 2 SD of +0.4 ± 1.6 mm for software-based measurements and +0.9 ± 2.9 mm and +0.7 ± 2.1 mm for readers 1 and 2, respectively. The intraclass correlation coefficient for interreader agreement was 0.9. Both software-based and radiologist-based measurements of colorectal cancer liver metastases are significantly larger on HBP than dual contrast images. Based on these findings, we recommend that longitudinal assessment be performed consistently on either HBP or dual contrast phases to avoid introduction of avoidable variability.

The combination of non-contrast abbreviated MRI and alpha foetoprotein has high performance for hepatocellular carcinoma screening

ObjectivesThis study aimed to compare two abbreviated MRI (AMRI) protocols to complete MRI for HCC detection: non-contrast (NC)-AMRI without/with alpha foetoprotein (AFP) and dynamic contrast-enhanced (Dyn)-AMRI.MethodsThis retrospective single-center study included 351 patients (M/F: 264/87, mean age: 57y) with chronic liver disease, who underwent MRI for HCC surveillance between 2014 and 2020. Two reconstructed AMRI sets were obtained based on complete MRI: NC-AMRI (T2-weighted imaging (WI) + diffusion-WI) and Dyn-AMRI (T2-WI + dynamic T1-WI) and were assessed by 2 radiologists who reported all suspicious lesions, using LI-RADS/adapted LI-RADS classification. The reference standard was based on all available patient data. Inter-reader agreement was assessed and MRI diagnostic performance was compared to the reference standard.ResultsThe reference standard demonstrated 83/351 HCC-positive patients (prevalence: 23.6%, median size: 22 mm, and positive MRIs: 83/631). Inter-reader agreement was substantial for all sets. Sensitivities of Dyn-AMRI and complete MRI (both 92.8%) were similar, higher than NC-AMRI (72.3%, p < 0.001). Specificities were not different between sets. NC-AMRI + AFP (92.8%) had similar sensitivity to Dyn-AMRI and complete MRI. In patients with small size HCCs (≤ 2 cm), sensitivities of Dyn-AMRI (85.3%) and complete MRI (88.2%) remained similar (p = 0.564), also outperforming NC-AMRI (52.9%, p < 0.05). NC-AMRI + AFP had similar sensitivity (88.2%) to Dyn-AMRI and complete MRI (p = 0.706 and p = 1, respectively).ConclusionsDyn-AMRI has similar diagnostic performance to complete MRI for HCC detection, while both outperform NC-AMRI, especially for small size HCCs. NC-AMRI + AFP demonstrates similar sensitivity to Dyn-AMRI and complete MRI.Clinical relevance statementDue to the low sensitivity of ultrasound for hepatocellular screening, new screening methods are needed. Abbreviated MRI (AMRI) is a candidate, especially non-contrast AMRI with serum alpha foetoprotein as the acquisition time is low, without the need for contrast medium injection.Key Points• Dynamic contrast-enhanced abbreviated MRI using extracellular gadolinium-based contrast agent and complete MRI have similar diagnostic performance for hepatocellular carcinoma detection in an at-risk population.• Non-contrast abbreviated MRI with alpha foetoprotein has similar diagnostic performance to dynamic contrast-enhanced abbreviated MRI and complete MRI, including when considering small size hepatocellular carcinoma ≤ 2 cm.• Non-contrast abbreviated MRI and dynamic contrast-enhanced abbreviated MRI can be performed in 7 and 10 min, excluding patient setup time.

Comparison of noncontrast, dynamic, and hepatobiliary phase abbreviated MRI protocols for detection of hepatic malignancies

BackgroundAbbreviated MRI for surveillance in patients at risk for hepatocellular carcinoma (HCC) has recently gained interest. PurposeTo compare the performance among the three types of abbreviated MRI protocols for the detection of hepatic malignancies in patients at risk for HCC. Material and methodsThis retrospective review using data from a prospective-registry study included 221 patients with one or more hepatic nodules detected during surveillance for chronic liver disease. Patients underwent MRI with extracellular contrast agents (ECA-MRI) and MRI with hepatobiliary agents (HBA-MRI) before surgery. Sequences from each MRI were extracted to create three simulated abbreviated MRI (aMRI) sets: noncontrast aMRI (NC-aMRI), dynamic aMRI (Dyn-aMRI), and hepatobiliary phase aMRI (HBP-aMRI). Two readers evaluated each set and reported the probability of malignancy and possibility of non-HCC malignancy per lesion. Using the pathology report as reference, the diagnostic performance of each aMRI was compared. ResultsThis study included 289 observations (219 HCCs, 22 non-HCC malignancies, and 48 benign lesions). Defining category definite malignancy as test positive, the performance of each aMRI was as follows: sensitivity, 94.6%, 88.8%, and 92.5%; and specificity, 83.3%, 91.7%, and 85.4% for HBP-aMRI, Dyn-aMRI, and NC-aMRI, respectively. Pairwise comparison revealed higher sensitivity of HBP-aMRI than both Dyn-aMRI (P = 0.003) and NC-aMRI (P = 0.025), and higher specificity of Dyn-aMRI than HBP-aMRI (P = 0.046). ConclusionHBP-aMRI showed better sensitivity than Dyn-aMRI or NC-aMRI, whereas the sensitivity of NC-aMRI was comparable to Dyn-aMRI in the detection of malignancy in high-risk patients. Dyn-aMRI showed better specificity than HBP-aMRI.

Intraindividual comparison of mris with extracellular and hepatobiliary contrast agents for the noninvasive diagnosis of hcc using Korean Liver Cancer Association-National Cancer Center 2022

Intraindividual comparison of mris with extracellular and hepatobiliary contrast agents for the noninvasive diagnosis of hcc using Korean Liver Cancer Association-National Cancer Center 2022

Detection of arterial phase hyperenhancement of small hepatocellular carcinoma with MRI: Comparison between single arterial and multi-arterial phases and between extracellular and hepatospecific contrast agents

PurposeThe purpose of this study was to compare the detection rate of arterial phase hyperenhancement (APHE) in small hepatocellular carcinoma (HCC) between single arterial phase (single-AP) and triple hepatic arterial (triple-AP) phase MRI and between extracellular (ECA) and hepato-specific (HBA) contrast agents. Materials and methodsA total of 109 cirrhotic patients with 136 HCCs from seven centers were included. There were 93 men and 16 women, with a mean age of 64.0 ± 8.9 (standard deviation) years (range: 42–82 years). Each patient underwent both ECA-MRI and HBA (gadoxetic acid)-MRI examination within one month of each other. Each MRI examination was retrospectively reviewed by two readers blinded to the second MRI examination. The sensitivities of triple- and single-AP for the detection of APHE were compared, and each phase of the triple-AP sequence was compared with the other two. ResultsNo differences in APHE detection were found between single-AP (97.2%; 69/71) and triple-AP (98.5%; 64/65) (P > 0.99) at ECA-MRI. No differences in APHE detection were found between single-AP (93%; 66/71) and triple-AP (100%; 65/65) at HBA-MRI (P = 0.12). Patient age, size of the nodules, use of automatic triggering, type of contrast agent, and type of sequence were not significantly associated with APHE detection. The reader was the single variable significantly associated with APHE detection. For triple-AP, best APHE detection rate was found for early and middle-AP images compared to late-AP images (P = 0.001 and P = 0.003). All APHEs were detected with the combination of early-AP and middle-AP images, except one that was detected on late-AP images by one reader. ConclusionOur study suggests that both single- and triple-AP can be used in liver MRI for the detection of small HCC especially when using ECA. Early AP and middle-AP are the most efficient phases and should be preferred for detecting APHE, regardless of the contrast agent used.

Gd-EOB MRI for HCC subtype differentiation in a western population according to the 5th edition of the World Health Organization classification.

To investigate the value of gadoxetic acid (Gd-EOB)-enhanced magnetic resonance imaging (MRI) for noninvasive subtype differentiation of HCCs according to the 5th edition of the WHO Classification of Digestive System Tumors in a western population. This retrospective study included 262 resected lesions in 240 patients with preoperative Gd-EOB-enhanced MRI. Subtypes were assigned by two pathologists. Gd-EOB-enhanced MRI datasets were assessed by two radiologists for qualitative and quantitative imaging features, including imaging features defined in LI-RADS v2018 and area of hepatobiliary phase (HBP) iso- to hyperintensity. The combination of non-rim arterial phase hyperenhancement with non-peripheral portal venous washout was more common in "not otherwise specified" (nos-ST) (88/168, 52%) than other subtypes, in particular macrotrabecular massive (mt-ST) (3/15, 20%), chromophobe (ch-ST) (1/8, 13%), and scirrhous subtypes (sc-ST) (2/9, 22%) (p = 0.035). Macrovascular invasion was associated with mt-ST (5/16, p = 0.033) and intralesional steatosis with steatohepatitic subtype (sh-ST) (28/32, p < 0.001). Predominant iso- to hyperintensity in the HBP was only present in nos-ST (16/174), sh-ST (3/33), and clear cell subtypes (cc-ST) (3/13) (p = 0.031). Associations were found for the following non-imaging parameters: age and sex, as patients with fibrolamellar subtype (fib-ST) were younger (median 44years (19-66), p < 0.001) and female (4/5, p = 0.023); logarithm of alpha-fetoprotein (AFP) was elevated in the mt-ST (median 397µg/l (74-5370), p < 0.001); type II diabetes mellitus was more frequent in the sh-ST (20/33, p = 0.027). Gd-EOB-MRI reproduces findings reported in the literature for extracellular contrast-enhanced MRI and CT and may be a valuable tool for noninvasive HCC subtype differentiation. Better characterization of the heterogeneous phenotypes of HCCaccording to the revised WHO classification potentially improves both diagnostic accuracy and the precision of therapeutic stratification for HCC. • Previously reported imaging features of common subtypes in CT and MRI enhanced with extracellular contrast agents are reproducible with Gd-EOB-enhanced MRI. • While uncommon, predominant iso- to hyperintensity in the HBP was observed only in NOS, clear cell, and steatohepatitic subtypes. • Gd-EOB-enhanced MRI offers imaging features that are of value for HCC subtype differentiation according to the 5th edition of the WHO Classification of Digestive System Tumors.

Evaluation of washout using subtraction MRI for the diagnosis of hepatocellular carcinoma in cirrhotic patients with spontaneously T1-hyperintense nodules

PurposeThe purpose of this study was to assess the value of subtraction imaging on post-arterial phase images (i.e., portal venous, delayed/transitional and hepatobiliary phases) for the non-invasive diagnosis of hepatocellular carcinoma (HCC) in spontaneously hyperintense nodules on T1-weighted imaging in patients with cirrhosis. Materials and methodsForty-five patients with a total 55 hepatic nodules that were spontaneously hyperintense on T1-weighted images were initially retrieved. All patients underwent MRI examination of the liver using extracellular agent. Each nodule was assessed for sensitivity and specificity using LI-RADS (Liver Imaging Reporting and Data System) during two reading sessions performed first without then with subtraction images on post-arterial phase images. The final standard of reference was defined by a step-by-step algorithm previously published combining histology, typical imaging, alfa fetoprotein and follow-up. ResultsForty-six nodules (26 HCC) in 39 patients with cirrhosis were analyzed. Using LI-RADS, the sensitivity and specificity for the diagnosis of HCC were 64% (95% CI: 41–83) and 67% (95% CI: 41–87) without subtraction; and 73% (95% CI: 50–89) (P > 0.999) and 33% (95% CI: 13–59) (P = 0.553) on subtraction imaging using extracellular contrast agent. Fifty-five percent (22/40) of nodules displayed a washout without subtraction and 70% (28/40) did so on subtraction imaging obtained with extracellular contrast agent. Twenty nodules out of 40 (50%) were classified LI-RADS 5 without subtraction, and 28 out of 40 nodules (70%) with subtraction. ConclusionThe results of this study suggest that the use of subtraction imaging on post-arterial phase images (i.e., PVP, DP/TP and HBP) is not relevant for the non-invasive diagnosis of HCC for spontaneously hyperintense nodules on T1-weighted images in patients with liver cirrhosis.

LI-RADS: Looking Back, Looking Forward.

Since its initial release in 2011, the Liver Imaging Reporting and Data System (LI-RADS) has evolved and expanded in scope. It started as a single algorithm for hepatocellular carcinoma (HCC) diagnosis with CT or MRI with extracellular contrast agents and has grown into a multialgorithm network covering all major liver imaging modalities and contexts of use. Furthermore, it has developed its own lexicon, report templates, and supplementary materials. This article highlights the major achievements of LI-RADS in the past 11 years, including adoption in clinical care and research across the globe, and complete unification of HCC diagnostic systems in the United States. Additionally, the authors discuss current gaps in knowledge, which include challenges in surveillance, diagnostic population definition, perceived complexity, limited sensitivity of LR-5 (definite HCC) category, management implications of indeterminate observations, challenges in reporting, and treatment response assessment following radiation-based therapies and systemic treatments. Finally, the authors discuss future directions, which will focus on mitigating the current challenges and incorporating advanced technologies. Tha authors envision that LI-RADS will ultimately transform into a probability-based system for diagnosis and prognostication of liver cancers that will integrate patient characteristics and quantitative imaging features, while accounting for imaging modality and contrast agent.