Current status of magnetic resonance imaging radiomics in hepatocellular carcinoma:A quantitative review with Radiomics Quality Score

BACKGROUND Radiomics is a promising tool that may increase the value of magnetic resonance imaging(MRI)for different tasks related to the management of patients with hepatocellular carcinoma(HCC).However,its implementation in clinical practice is still far,with many issues related to the methodological quality of radiomic studies.AIM To systematically review the current status of MRI radiomic studies concerning HCC using the Radiomics Quality Score(RQS).METHODS A systematic literature search of PubMed,Google Scholar,and Web of Science databases was performed to identify original articles focusing on the use of MRI radiomics for HCC management published between 2017 and 2023.The methodological quality of radiomic studies was assessed using the RQS tool.Spearman’s correlation(ρ)analysis was performed to explore if RQS was correlated with journal metrics and characteristics of the studies.The level of statistical significance was set at P<0.05.RESULTS One hundred and twenty-seven articles were included,of which 43 focused on HCC prognosis,39 on prediction of pathological findings,16 on prediction of the expression of molecular markers outcomes,18 had a diagnostic purpose,and 11 had multiple purposes.The mean RQS was 8±6.22,and the corresponding percentage was 24.15%±15.25%(ranging from 0.0% to 58.33%).RQS was positively correlated with journal impact factor(IF;ρ=0.36,P=2.98×10^(-5)),5-years IF(ρ=0.33,P=1.56×10^(-4)),number of patients included in the study(ρ=0.51,P<9.37×10^(-10))and number of radiomics features extracted in the study(ρ=0.59,P<4.59×10^(-13)),and time of publication(ρ=-0.23,P<0.0072).CONCLUSION Although MRI radiomics in HCC represents a promising tool to develop adequate personalized treatment as a noninvasive approach in HCC patients,our study revealed that studies in this field still lack the quality required to allow its introduction into clinical practice.

Simplified liver imaging reporting and data system for the diagnosis of hepatocellular carcinoma on gadoxetic acid-enhanced magnetic resonance imaging

BACKGROUND The liver imaging reporting and data system(LI-RADS)diagnostic table has 15 cells and is too complex.The diagnostic performance of LI-RADS for hepatocellular carcinoma(HCC)is not satisfactory on gadoxetic acid-enhanced magnetic resonance imaging(EOB-MRI).AIM To evaluate the ability of the simplified LI-RADS(sLI-RADS)to diagnose HCC on EOB-MRI.METHODS A total of 331 patients with 356 hepatic observations were retrospectively analysed.The diagnostic performance of sLI-RADS A-D using a single threshold was evaluated and compared with LI-RADS v2018 to determine the optimal sLIRADS.The algorithms of sLI-RADS A-D are as follows:The single threshold for sLI-RADS A and B was 10 mm,that is,classified observations≥10mm using an algorithm of 10-19 mm observations(sLI-RADS A)and≥20 mm observations(sLI-RADS B)in the diagnosis table of LI-RADS v2018,respectively,while the classification algorithm remained unchanged for observations<10 mm;the single threshold for sLI-RADS C and D was 20 mm,that is,for<20 mm observations,the algorithms for<10 mm observations(sLI-RADS C)and 10-19 mm observations(sLI-RADS D)were used,respectively,while the algorithm remained unchanged for observations≥20 mm.With hepatobiliary phase(HBP)hypointensity as a major feature(MF),the final sLI-RADS(F-sLI-RADS)was formed according to the optimal sLI-RADS,and its diagnostic performance was evaluated.The times needed to classify the observations according to F-sLIRADS and LI-RADS v2018 were compared.RESULTS The optimal sLI-RADS was sLI-RADS D(with a single threshold of 20 mm),because its sensitivity was greater than that of LI-RADS v2018(89.8%vs 87.0%,P=0.031),and its specificity was not lower(89.4%vs 90.1%,P>0.999).With HBP hypointensity as an MF,the sensitivity of F-sLI-RADS was greater than that of LI-RADS v2018(93.0%vs 87.0%,P<0.001)and sLI-RADS D(93.0%vs 89.8%,P=0.016),without a lower specificity(86.5%vs 90.1%,P=0.062;86.5%vs 89.4%,P=0.125).Compared with that of LI-RADS v2018,the time to classify lesions according to FsLI-RADS was shorter(51±21 s vs 73±24 s,P<0.001).CONCLUSION The use of sLI-RADS with HBP hypointensity as an MF may improve the sensitivity of HCC diagnosis and reduce lesion classification time.

Pre-operative enhanced magnetic resonance imaging combined with clinical features predict early recurrence of hepatocellular carcinoma after radical resection

BACKGROUND Indentifying predictive factors for postoperative recurrence of hepatocellular carcinoma(HCC)has great significance for patient prognosis.AIM To explore the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced magnetic resonance imaging(MRI)combined with clinical features in predicting early recurrence of HCC after resection.METHODS A total of 161 patients with pathologically confirmed HCC were enrolled.The patients were divided into early recurrence and non-early recurrence group based on the follow-up results.The clinical,laboratory,pathological results and Gd-EOB-DTPA enhanced MRI imaging features were analyzed.RESULTS Of 161 patients,73 had early recurrence and 88 were had non-early recurrence.Univariate analysis showed that patient age,gender,serum alpha-fetoprotein level,the Barcelona Clinic Liver Cancer stage,China liver cancer(CNLC)stage,microvascular invasion(MVI),pathological satellite focus,tumor size,tumor number,tumor boundary,tumor capsule,intratumoral necrosis,portal vein tumor thrombus,large vessel invasion,nonperipheral washout,peritumoral enhancement,hepatobiliary phase(HBP)/tumor signal intensity(SI)/peritumoral SI,HBP peritumoral low signal and peritumoral delay enhancement were significantly associated with early recurrence of HCC after operation.Multivariate logistic regression analysis showed that patient age,MVI,CNLC stage,tumor boundary and large vessel invasion were independent predictive factors.External data validation indicated that the area under the curve of the combined predictors was 0.861,suggesting that multivariate logistic regression was a reasonable predictive model for early recurrence of HCC.CONCLUSION Gd-EOB-DTPA enhanced MRI combined with clinical features would help predicting the early recurrence of HCC after operation.

Application of texture signatures based on multiparameter-magnetic resonance imaging for predicting microvascular invasion in hepatocellular carcinoma:Retrospective study

BACKGROUND Despite continuous changes in treatment methods,the survival rate for advanced hepatocellular carcinoma(HCC)patients remains low,highlighting the importance of diagnostic methods for HCC.AIM To explore the efficacy of texture analysis based on multi-parametric magnetic resonance(MR)imaging(MRI)in predicting microvascular invasion(MVI)in preoperative HCC.METHODS This study included 105 patients with pathologically confirmed HCC,categorized into MVI-positive and MVI-negative groups.We employed Original Data Analysis,Principal Component Analysis,Linear Discriminant Analysis(LDA),and Non-LDA(NDA)for texture analysis using multi-parametric MR images to predict preoperative MVI.The effectiveness of texture analysis was determined using the B11 program of the MaZda4.6 software,with results expressed as the misjudgment rate(MCR).RESULTS Texture analysis using multi-parametric MRI,particularly the MI+PA+F dimensionality reduction method combined with NDA discrimination,demonstrated the most effective prediction of MVI in HCC.Prediction accuracy in the pulse and equilibrium phases was 83.81%.MCRs for the combination of T2-weighted imaging(T2WI),arterial phase,portal venous phase,and equilibrium phase were 22.86%,16.19%,20.95%,and 20.95%,respectively.The area under the curve for predicting MVI positivity was 0.844,with a sensitivity of 77.19%and specificity of 91.67%.CONCLUSION Texture analysis of arterial phase images demonstrated superior predictive efficacy for MVI in HCC compared to T2WI,portal venous,and equilibrium phases.This study provides an objective,non-invasive method for preoperative prediction of MVI,offering a theoretical foundation for the selection of clinical therapy.

Nomogram prediction of vessels encapsulating tumor clusters in small hepatocellular carcinoma≤3 cm based on enhanced magnetic resonance imaging

BACKGROUND Vessels encapsulating tumor clusters(VETC)represent a recently discovered vascular pattern associated with novel metastasis mechanisms in hepatocellular carcinoma(HCC).However,it seems that no one have focused on predicting VETC status in small HCC(sHCC).This study aimed to develop a new nomogram for predicting VETC positivity using preoperative clinical data and image features in sHCC(≤3 cm)patients.AIM To construct a nomogram that combines preoperative clinical parameters and image features to predict patterns of VETC and evaluate the prognosis of sHCC patients.METHODS A total of 309 patients with sHCC,who underwent segmental resection and had their VETC status confirmed,were included in the study.These patients were recruited from three different hospitals:Hospital 1 contributed 177 patients for the training set,Hospital 2 provided 78 patients for the test set,and Hospital 3 provided 54 patients for the validation set.Independent predictors of VETC were identified through univariate and multivariate logistic analyses.These independent predictors were then used to construct a VETC prediction model for sHCC.The model’s performance was evaluated using the area under the curve(AUC),calibration curve,and clinical decision curve.Additionally,Kaplan-Meier survival analysis was performed to confirm whether the predicted VETC status by the model is associated with early recurrence,just as it is with the actual VETC status and early recurrence.RESULTS Alpha-fetoprotein_lg10,carbohydrate antigen 199,irregular shape,non-smooth margin,and arterial peritumoral enhancement were identified as independent predictors of VETC.The model incorporating these predictors demonstrated strong predictive performance.The AUC was 0.811 for the training set,0.800 for the test set,and 0.791 for the validation set.The calibration curve indicated that the predicted probability was consistent with the actual VETC status in all three sets.Furthermore,the decision curve analysis demonstrated the clinical benefits of our model for patients with sHCC.Finally,early recurrence was more likely to occur in the VETC-positive group compared to the VETC-negative group,regardless of whether considering the actual or predicted VETC status.CONCLUSION Our novel prediction model demonstrates strong performance in predicting VETC positivity in sHCC(≤3 cm)patients,and it holds potential for predicting early recurrence.This model equips clinicians with valuable information to make informed clinical treatment decisions.

Preoperative prediction of hepatocellular carcinoma microvascular invasion based on magnetic resonance imaging feature extraction artificial neural network

BACKGROUND Hepatocellular carcinoma(HCC)recurrence is highly correlated with increased mortality.Microvascular invasion(MVI)is indicative of aggressive tumor biology in HCC.AIM To construct an artificial neural network(ANN)capable of accurately predicting MVI presence in HCC using magnetic resonance imaging.METHODS This study included 255 patients with HCC with tumors<3 cm.Radiologists annotated the tumors on the T1-weighted plain MR images.Subsequently,a three-layer ANN was constructed using image features as inputs to predict MVI status in patients with HCC.Postoperative pathological examination is considered the gold standard for determining MVI.Receiver operating characteristic analysis was used to evaluate the effectiveness of the algorithm.RESULTS Using the bagging strategy to vote for 50 classifier classification results,a prediction model yielded an area under the curve(AUC)of 0.79.Moreover,correlation analysis revealed that alpha-fetoprotein values and tumor volume were not significantly correlated with the occurrence of MVI,whereas tumor sphericity was significantly correlated with MVI(P<0.01).CONCLUSION Analysis of variable correlations regarding MVI in tumors with diameters<3 cm should prioritize tumor sphericity.The ANN model demonstrated strong predictive MVI for patients with HCC(AUC=0.79).

Predicting distant metastasis in nasopharyngeal carcinoma using gradient boosting tree model based on detailed magnetic resonance imaging reports

BACKGROUND Development of distant metastasis(DM)is a major concern during treatment of nasopharyngeal carcinoma(NPC).However,studies have demonstrated im-proved distant control and survival in patients with advanced NPC with the addition of chemotherapy to concomitant chemoradiotherapy.Therefore,precise prediction of metastasis in patients with NPC is crucial.AIM To develop a predictive model for metastasis in NPC using detailed magnetic resonance imaging(MRI)reports.METHODS This retrospective study included 792 patients with non-distant metastatic NPC.A total of 469 imaging variables were obtained from detailed MRI reports.Data were stratified and randomly split into training(50%)and testing sets.Gradient boosting tree(GBT)models were built and used to select variables for predicting DM.A full model comprising all variables and a reduced model with the top-five variables were built.Model performance was assessed by area under the curve(AUC).RESULTS Among the 792 patients,94 developed DM during follow-up.The number of metastatic cervical nodes(30.9%),tumor invasion in the posterior half of the nasal cavity(9.7%),two sides of the pharyngeal recess(6.2%),tubal torus(3.3%),and single side of the parapharyngeal space(2.7%)were the top-five contributors for predicting DM,based on their relative importance in GBT models.The testing AUC of the full model was 0.75(95%confidence interval[CI]:0.69-0.82).The testing AUC of the reduced model was 0.75(95%CI:0.68-0.82).For the whole dataset,the full(AUC=0.76,95%CI:0.72-0.82)and reduced models(AUC=0.76,95%CI:0.71-0.81)outperformed the tumor node-staging system(AUC=0.67,95%CI:0.61-0.73).CONCLUSION The GBT model outperformed the tumor node-staging system in predicting metastasis in NPC.The number of metastatic cervical nodes was identified as the principal contributing variable.

Secondary rectal linitis plastica caused by prostatic adenocarcinoma-magnetic resonance imaging findings and dissemination pathways:A case report

BACKGROUND Secondary rectal linitis plastica(RLP)from prostatic adenocarcinoma is a rare and poorly understood form of metastatic spread,characterized by a desmoplastic response and concentric rectal wall infiltration with mucosal preservation.This complicates endoscopic diagnosis and can mimic gastrointestinal malignancies.This case series underscores the critical role of magnetic resonance imaging(MRI)in identifying the distinct imaging features of RLP and highlights the importance of considering this condition in the differential diagnosis of patients with a history of prostate cancer.CASE SUMMARY Three patients with secondary RLP due to prostatic adenocarcinoma presented with varied clinical features.The first patient,a 76-year-old man with advanced prostate cancer,had rectal pain and incontinence.MRI showed diffuse prostatic invasion and significant rectal wall thickening with a characteristic"target sign"pattern.The second,a 57-year-old asymptomatic man with elevated prostatespecific antigen levels and a history of prostate cancer exhibited rectoprostatic angle involvement and rectal wall thickening on MRI,with positron emission tomography/computed tomography PSMA confirming the prostatic origin of the metastatic spread.The third patient,an 80-year-old post-radical prostatectomy,presented with refractory constipation.MRI revealed a neoplastic mass infiltrating the rectal wall.In all cases,MRI consistently showed stratified thickening,concentric signal changes,restricted diffusion,and contrast enhancement,which were essential for diagnosing secondary RLP.Biopsies confirmed the prostatic origin of the neoplastic involvement in the rectum.CONCLUSION Recognizing MRI findings of secondary RLP is essential for accurate diagnosis and management in prostate cancer patients.

Unusual magnetic resonance imaging findings of brain and leptomeningeal metastasis in lung adenocarcinoma:A case report

BACKGROUND Metastatic tumors are the most common malignancies of central nervous system in adults,and the frequent primary lesion is lung cancer.Brain and leptomeningeal metastases are more common in patients with non-small-cell lung cancer harboring epidermal growth factor receptor mutations.However,the coexist of brain metastasis with leptomeningeal metastasis(LM)in isolated gyriform appearance is rare.CASE SUMMARY We herein presented a case of a 76-year-old male with an established diagnosis as lung adenocarcinoma with gyriform-appeared cerebral parenchymal and leptomeningeal metastases,accompanied by mild peripheral edema and avid contrast enhancement on magnetic resonance imaging.Surgical and pathological examinations confirmed the brain and leptomeningeal metastatic lesions in the left frontal cortex,subcortical white matter and local leptomeninges.CONCLUSION This case was unique with respect to the imaging findings of focal gyriform appearance,which might be caused by secondary parenchymal brain metastatic tumors invading into the leptomeninges or coexistence with LM.Radiologists should be aware of this uncommon imaging presentation of tumor metastases to the central nervous system.

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.

Advances in computed tomography and magnetic resonance imaging of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common primary liver cancer.Imaging is important for establishing a diagnosis of HCC and early diagnosis is imperative as several potentially curative treatments are available when HCC is small.Hepatocarcinogenesis occurs in a stepwise manner on a background of chronic liver disease or cirrhosis wherein multiple genes are altered resulting in a range of cirrhosisassociated nodules.This progression is related to increased cellularity,neovascularity and size of the nodule.An understanding of the stepwise progression may aid in early diagnosis.Dynamic and multiphase contrast-enhanced computed tomography and magnetic resonance imaging still form the cornerstone in the diagnosis of HCC.An overview of the current diagnostic standards of HCC in accordance to the more common practicing guidelines and their differences will be reviewed.Ancillary features contribute to diagnostic confidence and has been incorporated into the more recent Liver Imaging Reporting and Data System.The use of hepatocyte-specific contrast agents is increasing and gradually changing the standard of diagnosis of HCC;the most significant benefit being the lack of uptake in the hepatocyte phase in the earlier stages of HCC progression.An outline of supplementary techniques in the imaging of HCC will also be reviewed.

Magnetic resonance imaging staging of nasopharyngeal carcinoma in the head and neck

Magnetic resonance imaging (MRI) is the modality of choice for staging nasopharyngeal carcinoma in the head and neck. This article will review the patterns of primary and nodal spread on MRI with reference to the latest 7th edition of the International Union Against Cancer/American Joint Committee on Cancer staging system.

Differentiation of hepatocellular carcinoma from its variousmimickers in liver magnetic resonance imaging:What arethe tips when using hepatocyte-specific agents?

Hepatocellular carcinoma is the most common primary hepatic malignant tumor.With widespread use of liver imaging,various cirrhosis-related nodules are frequently detected in patients with chronic liver disease,while diverse hypervascular hepatic lesions are incidentally detected but undiagnosed on dynamic computed tomography and magnetic resonance imaging(MRI).However,use of hepatocyte-specific MR contrast agents with combined perfusion and hepatocyte-selective properties have improved diagnostic performance in detection and characterization of focal liver lesions.Meanwhile,the enhancement patterns observed during dynamic phases using hepatocyte-specific agents may be different from those observed during MRI using conventional extracellular fluid agents,leading to confusion in diagnosis.Therefore,we discuss useful tips for the differentiation of hepatocellular carcinoma from similar lesions in patients with and without chronic liver disease using liver MRI with hepatocyte-specific agents.

Gadoxetic acid-enhanced magnetic resonance imaging can predict the pathologic stage of solitary hepatocellular carcinoma

BACKGROUND Although important for determining long-term outcome, pathologic stage of hepatocellular carcinoma (HCC) is difficult to predict before surgery. Current state-of-the-art magnetic resonance imaging (MRI) using gadoxetic acid provides many imaging features that could potentially be used to classify single HCC as pT1 or pT2. AIM To determine which gadoxetic acid-enhanced MRI (EOB-MRI) findings predict pathologic stage T2 in patients with solitary HCC (cT1). METHODS Pre-operative EOB-MRI findings were reviewed in a retrospective cohort of patients with solitary HCC. The following imaging features were examined: Hyperintensity in unenhanced T2-weighted images, hypointensity in unenhanced T1-weighted images, arterial enhancement, corona enhancement, washout appearance, capsular appearance, hypointensity in the tumor tissue during the hepatobiliary (HB) phase, peritumoral hypointensity in the HB phase, hypointense rim in the HB phase, intratumoral fat, hyperintensity on diffusionweighted imaging, hypointensity on apparent diffusion coefficient map, mosaic appearance, nodule-in-nodule appearance, and the margin (smooth or irregular). Surgical pathology was used as the reference method for tumor staging. Univariate and multivariate analyses were performed to identify predictors of microvascular invasion or satellite nodules. RESULTS There were 39 (34.2%;39 of 114) and 75 (65.8%;75 of 114) pathological stage T2 and T1 HCCs, respectively. Large tumor size (≥ 2.3 cm) and two MRI findings, i.e., corona enhancement [odds ratio = 2.67;95% confidence interval: 1.101-6.480] and peritumoral hypointensity in HB phase images (odds ratio = 2.203;95% confidence interval: 0.961-5.049) were associated with high risk of pT2 HCC. The positive likelihood ratio was 6.25 (95% confidence interval: 1.788-21.845), and sensitivity of EOB-MRI for detecting pT2 HCC was 86.2% when two or three of these MRI features were present. Small tumor size and hypointense rim in the HB phase were regarded as benign features. Small HCCs with hypointense rim but not associated with aggressive features were mostly pT1 lesions (specificity, 100%). CONCLUSION Imaging features on EOB-MRI could potentially be used to predict the pathologic stage of solitary HCC (cT1) as pT1 or pT2.

Hepatocellular carcinoma: Can LI-RADS v2017 with gadoxetic-acid enhancement magnetic resonance and diffusion-weighted imaging improve diagnostic accuracy?

BACKGROUND The Liver Imaging Reporting and Data System(LI-RADS), supported by the American College of Radiology(ACR), has been developed for standardizing the acquisition, interpretation, reporting, and data collection of liver imaging examinations in patients at risk for hepatocellular carcinoma(HCC). Diffusionweighted imaging(DWI), which is described as an ancillary imaging feature of LI-RADS, can improve the diagnostic efficiency of LI-RADS v2017 with gadoxetic acid-enhanced magnetic resonance imaging(MRI) for HCC.AIM To determine whether the use of DWI can improve the diagnostic efficiency of LIRADS v2017 with gadoxetic acid-enhanced magnetic resonance MRI for HCC.METHODS In this institutional review board-approved study, 245 observations of high risk of HCC were retrospectively acquired from 203 patients who underwent gadoxetic acid-enhanced MRI from October 2013 to April 2018. Two readers independently measured the maximum diameter and recorded the presence of each lesion and assigned scores according to LI-RADS v2017. The test was used to determine the agreement between the two readers with or without DWI. In addition, the sensitivity(SE), specificity(SP), accuracy(AC), positive predictive value(PPV), and negative predictive value(NPV) of LI-RADS were calculated.Youden index values were used to compare the diagnostic performance of LIRADS with or without DWI.RESULTS Almost perfect interobserver agreement was obtained for the categorization of observations with LI-RADS(kappa value: 0.813 without DWI and 0.882 with DWI). For LR-5, the diagnostic SE, SP, and AC values were 61.2%, 92.5%, and71.4%, respectively, with or without DWI; for LR-4/5, they were 73.9%, 80%, and75.9% without DWI and 87.9%, 80%, and 85.3% with DWI; for LR-4/5/M, they were 75.8%, 58.8%, and 70.2% without DWI and 87.9%, 58.8%, and 78.4% with DWI; for LR-4/5/TIV, they were 75.8%, 75%, and 75.5% without DWI and 89.7%,75%, and 84.9% with DWI. The Youden index values of the LI-RADS classification without or with DWI were as follows: LR-4/5: 0.539 vs 0.679; LR-4/5/M: 0.346 vs 0.467; and LR-4/5/TIV: 0.508 vs 0.647.CONCLUSION LI-RADS v2017 has been successfully applied with gadoxetate-enhanced MRI for patients at high risk for HCC. The addition of DWI significantly increases the diagnostic efficiency for HCC.

Detection of small hepatocellular carcinoma:Comparison of dynamic enhancement magnetic resonance imaging and multiphase multirow-detector helical CT scanning

AIM: To compare the gadolinium-enhanced multiphase dynamic magnetic resonance imaging (MRI) and multiphase multirow-detector helical CT (MDCT) scanning for detection of small hepatocellular carcinoma (HCC). METHODS: MDCT scanning and baseline MRI with SE T1-WI and T2-WI sequence combined with FMPSPGR sequence were performed in 37 patients with 43 small HCCs. Receiver operating characteristic (ROC) curves were plotted to analyze the results for modality. RESULTS: The areas below ROC curve (Az) were calculated. There was no statistical difference in dynamic enhancement MDCT and MRI. The detection rate of small HCC was 97.5%-97.6% on multiphase MDCT scanning and 90.7%-94.7% on MRI, respectively. The sensitivity of detection for small HCC on MDCT scanning was higher than that on dynamic enhancement MRI. The sensitivity of detection for minute HCC (tumor diameter ≤ 1 cm) was 90.0%-95.0% on MDCT scanning and 70.0%-85.0% on MRI, respectively. CONCLUSION: MDCT scanning should be performed for early detection and effective treatment of small HCC in patients with chronic hepatitis and cirrhosis during follow-up.

Magnetic resonance imaging-guided percutaneous cryoablation of hepatocellular carcinoma in special regions

BACKGROUND: Local cryoablation guided by CT or ultrasound has been widely applied in the treatment of hepatocellular carcinoma. However, it is still difficult to apply this technique in certain regions such as the diaphragm dome, the first hepatic hilum, and regions adjacent to the gallbladder. This study aimed to evaluate the safety and efficacy of using magnetic resonance imaging (MRI)-guided percutaneous cryoablation as well as the effect of using an open MRI system in guiding and monitoring the treatment of hepatocellular carcinoma in these regions. METHODS: Cryoablation, guided by an open 0.35T MRI scanner and with the assistance of an MRI-compatible optical navigation system, was performed on 32 patients with hepatocellular carcinoma at the diaphragm dome, the first hepatic hilum, and regions adjacent to the gallbladder. Each patient had one or two tumors. The total number of tumors treated was 36. The tumor diameters ranged from 2.5 to 10.0 cm (mean 4.7+/-1.8 cm). The cryosurgical system was MRI-compatible and equipped with cryoprobes 1.47 mm in outside diameter. Under the guidance of MRI in combination with the optical navigation system, the cryoprobes were introduced percutaneously into a tumor at the planned targeting points while critical organs or tissues were avoided. Each cryoablation procedure included two freezing-thawing cycles, and MRI images were acquired dynamically to monitor the ablation of the tumor from time to time during the operation. In order to investigate the therapeutic effects of a cryoablation procedure, AFP measurements and liver-enhanced MRI or CT-enhanced scans were performed at regular times. RESULTS: MRI and optical navigation system-guided cryoablation procedures were successfully performed on all 32 patients (36 tumor sites) and no serious complications occurred. The follow-up period ranged from 5 to 12 months. The 6- and 12-month overall survival rates were 96.8% and 90.6%, respectively. According to the diagnosis of liver-enhanced MRI scans, 10 patients (31.3%) had complete ablation, 18 (56.3%) partial ablation (>80%), 3 (9.4%) stable disease (>50% ablation), and 1 (3.1%) progressive disease (a new tumor site in the liver). The overall efficacy was 87.5%. CONCLUSIONS: MR-guided percutaneous cryoablation using optical navigation is a safe and effective minimally invasive procedure for the treatment of hepatocellular carcinoma at certain special regions, which is difficult to treat with other imaging guidance approaches. With its unique and superb imaging functions, MRI plays an important role in the display, guidance, and monitoring of the cryoablation procedure in treating hepatocellular carcinoma at these special regions. Equipped with an MRI-compatible optical navigation system, MRI-guided therapy makes the cryoablation procedure more precise and safe.

Development and in vitro study of a bi-specific magnetic resonance imaging molecular probe for hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)ranks second in terms of cancer mortality worldwide.Molecular magnetic resonance imaging(MRI)targeting HCC biomarkers such as alpha-fetoprotein(AFP)or glypican-3(GPC3)offers new strategies to enhance specificity and help early diagnosis of HCC.However,the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3,which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors<1 cm(MHCC).We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC diagnosis.AIM To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular level.METHODS A double antigen-targeted MRI probe for MHCC anti-AFP-USPIO-anti-GPC3(UAG)was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle(USPIO).At the same time,the singly labeled probes of anti-AFP-USPIO(UA)and anti-GPC3-USPIO(UG)and non-targeted USPIO(U)were also prepared for comparison.The physical characterization including morphology(transmission electron microscopy),hydrodynamic size,and zeta potential(dynamic light scattering)was conducted for each of the probes.The antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/GPC3.First,AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and immunocytochemistry.Then,the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI(T2-weighted and T2-map)with a 3.0 Tesla clinical MR scanner.RESULTS Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-6/GPC3 cells expressing AFP and GPC3 antigens compared with single antibody-conjugated and unconjugated USPIO probes.The iron Prussian blue staining and quantitative T2-map MRI analysis showed that,compared with UA,UG,and U,the uptake of double antigen-targeted UAG probe demonstrated a 23.3%(vs UA),15.4%(vs UG),and 57.3%(vs U)increased Prussian stained cell percentage and a 14.93%(vs UA),9.38%(vs UG),and 15.3%(vs U)reduction of T2 relaxation time,respectively.Such bi-specific probe might have the potential to overcome tumor heterogeneity.Meanwhile,the coupling of two antibodies did not influence the magnetic performance of USPIO,and the relatively small hydrodynamic size(59.60±1.87 nm)of double antibodyconjugated USPIO probe makes it a viable candidate for use in MHCC MRI in vivo,as they are slowly phagocytosed by macrophages.CONCLUSION The bi-specific probe presents enhanced targeting efficiency and MRI sensitivity to HCC cells than singly-or non-targeted USPIO,paving the way for in vivo translation to further evaluate its clinical potential.

Optimization of hepatobiliary phase delay time of Gd-EOB-DTPA-enhanced magnetic resonance imaging for identification of hepatocellular carcinoma in patients with cirrhosis of different degrees of severity

AIM To optimize the hepatobiliary phase delay time(HBPDT) of Gd-EOB-DTPA-enhanced magnetic resonance imaging(GED-MRI) for more efficient identification of hepatocellular carcinoma(HCC) occurring in different degrees of cirrhosis assessed by Child-Pugh(CP) score.METHODS The liver parenchyma signal intensity(LPSI), the liver parenchyma(LP)/HCC signal ratios, and the visibility of HCC at HBP-DT of 5, 10, 15, 20, and 25 min(i.e., DT-5, DT-10, DT-15, DT-20, and DT-25) after injection of GdEOB-DTPA were collected and analyzed in 73 patients with cirrhosis of different degrees of severity(including 42 patients suffering from HCC) and 18 healthy adult controls.RESULTS The LPSI increased with HBP-DT more significantly in the healthy group than in the cirrhosis group(F = 17.361, P < 0.001). The LP/HCC signal ratios had a significant difference(F = 12.453, P < 0.001) among various HBP-DT points, as well as between CP-A and CP-B/C subgroups(F = 9.761, P < 0.001). The constituent ratios of HCC foci identified as obvious hypointensity(+++), moderate hypointensity(++), and mild hypointensity or isointensity(+/-) kept stable from DT-10 to DT-25: 90.6%, 9.4%, and 0.0% in the CP-A subgroup; 50.0%, 50.0%, and 0.0% in the CP-B subgroup; and 0.0%, 0.0%, and 100.0% in the CP-C subgroup, respectively.CONCLUSION The severity of liver cirrhosis has significant negative influence on the HCC visualization by GED-MRI. DT-10 is more efficient and practical than other HBP-DT points to identify most of HCC foci emerging in CP-A cirrhosis, as well as in CP-B cirrhosis; but an HBP-DT of 15 min or longer seems more appropriate than DT-10 for visualization of HCC in patients with CP-C cirrhosis.

Dual-input two-compartment pharmacokinetic model of dynamic contrast-enhanced magnetic resonance imaging in hepatocellular carcinoma

AIM: To investigate the feasibility of a dual-input two-compartment tracer kinetic model for evaluating tumorous microvascular properties in advanced hepatocellular carcinoma(HCC). METHODS: From January 2014 to April 2015, we prospectively measured and analyzed pharmacokinetic parameters [transfer constant(K_(trans)), plasma flow(F_p), permeability surface area product(PS), efflux rate constant(k_(ep)), extravascular extracellular space volume ratio(V_e), blood plasma volume ratio(V_p), and hepatic perfusion index(HPI)] using dual-input two-compartment tracer kinetic models [a dual-input extended Tofts model and a dual-input 2-compartment exchange model(2CXM)] in 28 consecutive HCC patients. A well-known consensus that HCC is a hypervascular tumor supplied by the hepatic artery and the portal vein was used as a reference standard. A paired Student's t-test and a nonparametric paired Wilcoxon rank sum test were used to compare the equivalent pharmacokinetic parameters derived from the two models, and Pearson correlation analysis was also applied to observe the correlations among all equivalent parameters. The tumor size and pharmacokinetic parameters were tested by Pearson correlation analysis, while correlations among stage, tumor size and all pharmacokinetic parameters were assessed by Spearman correlation analysis. RESULTS: The F_p value was greater than the PS value(F_P = 1.07 m L/m L per minute, PS = 0.19 m L/m L per minute) in the dual-input 2CXM; HPI was 0.66 and 0.63 in the dual-input extended Tofts model and the dualinput 2CXM, respectively. There were no significant differences in the K_(ep), V_p, or HPI between the dual-input extended Tofts model and the dual-input 2CXM(P = 0.524, 0.569, and 0.622, respectively). All equivalent pharmacokinetic parameters, except for V_e, were correlated in the two dual-input two-compartment pharmacokinetic models; both Fp and PS in the dualinput 2CXM were correlated with K_(trans) derived from the dual-input extended Tofts model(P = 0.002, r = 0.566; P = 0.002, r = 0.570); K_(ep), V_p, and HPI between the two kinetic models were positively correlated(P = 0.001, r = 0.594; P = 0.0001, r = 0.686; P = 0.04, r = 0.391, respectively). In the dual input extended Tofts model, V_e was significantly less than that in the dual input 2CXM(P = 0.004), and no significant correlation was seen between the two tracer kinetic models(P = 0.156, r = 0.276). Neither tumor size nor tumor stage was significantly correlated with any of the pharmacokinetic parameters obtained from the two models(P > 0.05).CONCLUSION: A dual-input two-compartment pharmacokinetic model(a dual-input extended Tofts model and a dual-input 2CXM) can be used in assessing the microvascular physiopathological properties before the treatment of advanced HCC. The dual-input extended Tofts model may be more stable in measuring the V_e; however, the dual-input 2CXM may be more detailed and accurate in measuring microvascular permeability.