MRI radiomics to monitor therapeutic outcome of sorafenib plus IHA transcatheter NK cell combination therapy in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common liver malignancy with limited treatment options. Previous studies expressed the potential synergy of sorafenib and NK cell immunotherapy as a promising approach against HCC. MRI is commonly used to assess response of HCC to therapy. However, traditional MRI-based metrics for treatment efficacy are inadequate for capturing complex changes in the tumor microenvironment, especially with immunotherapy. In this study, we investigated potent MRI radiomics analysis to non-invasively assess early responses to combined sorafenib and NK cell therapy in a HCC rat model, aiming to predict multiple treatment outcomes and optimize HCC treatment evaluations. METHODS: Sprague Dawley (SD) rats underwent tumor implantation with the N1-S1 cell line. Tumor progression and treatment efficacy were assessed using MRI following NK cell immunotherapy and sorafenib administration. Radiomics features were extracted, processed, and selected from both T1w and T2w MRI images. The quantitative models were developed to predict treatment outcomes and their performances were evaluated with area under the receiver operating characteristic (AUROC) curve. Additionally, multivariable linear regression models were constructed to determine the correlation between MRI radiomics and histology, aiming for a noninvasive evaluation of tumor biomarkers. These models were evaluated using root-mean-squared-error (RMSE) and the Spearman correlation coefficient. RESULTS: A total of 743 radiomics features were extracted from T1w and T2w MRI data separately. Subsequently, a feature selection process was conducted to identify a subset of five features for modeling. For therapeutic prediction, four classification models were developed. Support vector machine (SVM) model, utilizing combined T1w + T2w MRI data, achieved 96% accuracy and an AUROC of 1.00 in differentiating the control and treatment groups. For multi-class treatment outcome prediction, Linear regression model attained 85% accuracy and an AUC of 0.93. Histological analysis showed that combination therapy of NK cell and sorafenib had the lowest tumor cell viability and the highest NK cell activity. Correlation analyses between MRI features and histological biomarkers indicated robust relationships (r = 0.94). CONCLUSIONS: Our study underscored the significant potential of texture-based MRI imaging features in the early assessment of multiple HCC treatment outcomes.

Glucose-Regulated Protein 78 Targeting ICG and DOX Loaded Hollow Fe3O4 Nanoparticles for Hepatocellular Carcinoma Diagnosis and Therapy.

Purpose: Liver cancer is considered as the third leading cause of cancer-related deaths, with hepatocellular carcinoma (HCC) accounting for approximately 90% of liver cancers. Improving the treatment of HCC is a serious challenge today. The primary objective of this study was to construct SP94-Fe3O4@ICG&DOX nanoparticles and investigate their potential diagnosis and treatment effect benefits on HCC. Methods: Firstly, we synthesized and characterized SP94-Fe3O4@ICG&DOX nanoparticles and confirmed their in vitro release behavior, photothermal and photodynamic performance. Moreover, the in vivo imaging capability was also observed. Finally, the inhibitory effects on Hepa1-6 in vitro and in vivo were observed as well as biosafety. Results: SP94-Fe3O4@ICG&DOX nanoparticles have a size of ~22.1 nm, with an encapsulation efficiency of 45.2% for ICG and 42.7% for DOX, showing excellent in vivo MPI and fluorescence imaging capabilities for precise tumor localization, and synergistic photo-chemotherapy (pH- and thermal-sensitive drug release) against tumors under irradiation. With the assistance of a fluorescence molecular imaging system or MPI scanner, the location and contours of the tumor were clearly visible. Under a constant laser irradiation (808 nm, 0.6 W/cm2) and a set concentration (50 µg/mL), the temperature of the solution could rapidly increase to ~45 °C, which could effectively kill the tumor cells. It could be effectively uptaken by HCC cells and significantly inhibit their proliferation under the laser irradiation (100% inhibition rate for HCC tumors). And most importantly, our nanoparticles exhibited favorable biocompatibility with normal tissues and cells. Conclusion: This versatile agent can serve as an intelligent and promising nanoplatform that integrates multiple accurate diagnoses, precise positioning of cancer tissue, and effective coordination with synergistic tumor photodynamic therapy.

Differences in the Diagnosis and Treatment of Patients with Early-Stage Hepatocellular Liver Cancer by Multi-Row Spiral CTMDCT and Gd-EOB-DTPA-Enhanced MRI.

Objective: The assessment of liver cancer lesion characteristics mainly relies on multi-row spiral computed tomography (MDCT) and magnetic resonance imaging (MRI). MDCT suffers from a series of problems, such as low soft tissue contrast and large tumor boundary errors, which lead to its limited practical application value in liver cancer. In contrast, Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI has better soft-tissue contrast than MDCT and increases the clarity of liver cancer lesions. To investigate the differences between MDCT and Gd-EOB-DTPA-enhanced MRI in managing patients with hepatocellular liver cancer. Methods: A total of 80 patients diagnosed with hepatocellular carcinoma of the liver, who received treatment at our hospital between September 2020 and September 2022, were included in this study. These patients were evenly divided into two groups: the observation group and the control group, with 40 cases in each. The aim of this study was to compare the differences in signal indices of hepatobiliary stage between the two groups in patients with hepatocellular carcinoma. Results: A total of 89 cancer nodules were detected in patients by MDCT, and 109 cancer nodules were detected in patients by Gd-EOB-DTPA-enhanced MRI. When the number of nodules detected by both imaging modalities was statistically analyzed, the differences in the number of hepatocellular carcinoma (HCC) nodules detected by MDCT and Gd-EOB-DTPA-enhanced MRI were statistically significant (P < .05). Further analysis of the data by single cancer nodule, multiple cancer nodules, and cancer nodule size showed that the difference between the two imaging modalities was statistically significant (P < .05) in the diagnosis of patients with a single liver cancer nodule or multiple liver cancer nodules (94.8% vs.81.3%). The difference in the comparison was statistically significant (P < .05). Conclusion: Gd-EOB-DTPA-enhanced MRI demonstrates superior diagnostic efficacy in detecting small hepatocellular carcinoma, offers improved staging capabilities for hepatocellular carcinoma, and provides more precise guidance for treatment planning.Consequently, Gd-EOB-DTPA-enhanced MRI exhibits exceptional diagnostic value and serves as a valuable tool for guiding treatment decisions in patients with hepatocellular carcinoma.

C-Arm Computed Tomographic Image Fusion for Repetitive Transarterial Chemoembolization of Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to evaluate the potential implications of fusion imaging with C-arm computed tomography (CACT) scans for repetitive conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma. MATERIALS AND METHODS: Fifty-six cTACE sessions were performed using fusion CACT images from September 2020 to June 2021 in a tertiary referral center, and the data were retrospectively analyzed. Fusion of unenhanced and enhanced CACT images was considered when previously accumulated iodized oil hampered the identification of local tumor progression or intrahepatic distant metastasis (indication A), when a tumor was supplied by multiple arteries with different origins from the aorta and missing tumor enhancement was suspected (indication B), or when iodized oil distribution on immediate post-cTACE CACT images needed to be precisely compared with the pre-cTACE images (indication C). Fusion image quality, initial tumor response, time to local progression (TTLP) of index tumors, and time to progression (TTP) were evaluated. RESULTS: The fusion quality was satisfactory with a mean misregistration distance of 1.4 mm. For the 40 patients with indication A, the initial tumor responses at 3 months were nonviable, equivocal, and viable in 27 (67.5%), 4 (10.0%), and 9 (22.5%) index tumors, respectively. The median TTLP and TTP were 14.8 months and 4.5 months, respectively. For 10 patients with indication B, the median TTLP and TTP were 8.3 months and 2.6 months, respectively. Among the 6 patients with indication C, 2 patients were additionally treated at the same cTACE session after confirming incomplete iodized oil uptake on fusion imaging. CONCLUSIONS: Fusion CACT images are useful in patients with hepatocellular carcinoma undergoing repetitive cTACE.

Quantitative Assessment of Lipiodol-Related Artifact Reduction for Dual-Energy Computed Tomography After Transcatheter Arterial Chemoembolization: A Phantom Study Evaluating the Use of Metal Artifact Reduction Algorithms.

OBJECTIVE: This study used metal artifact reduction (MAR) software to examine the computed tomography (CT) number of dual-energy CT (DECT) of hepatocellular carcinoma after transcatheter arterial chemoembolization. METHODS: Hollow columnar acrylic phantoms were filled with lipiodol and inserts of 2 sizes (large and small) were used to simulate liver tumors on a Revolution GSI CT scanner. The CT numbers of a single test object were collected twice: once with and once without the MAR algorithm. Lipiodol beam-hardening artifacts were quantified by measuring CT numbers in a region of interest around the tumor-simulating insert. RESULTS: The virtual monochromatic CT numbers of large and small tumors were closely related to energy. For small tumors, CT numbers increased with energy. For large tumors, CT numbers increased with energy at 1 cm from the margin but decreased with an increase in energy at 5 cm. Regardless of the size, distance, or location of the tumor, the CT numbers fluctuated more at low energy levels. CONCLUSIONS: At 1 cm from the margin, the CT numbers with MAR were significantly different from those without MAR. Low-energy CT numbers with MAR were near reference values. Metal artifact reduction exhibited superior performance for small tumors. Tumor margin images are affected by artifacts caused by Lipiodol. However, with MAR, CT numbers can be effectively calibrated, thus enabling clinicians to more accurately evaluate hepatocellular carcinoma development and identify residual tumors and recurrent or metastatic lesions.

Near infrared-emitting multimodal nanosystem for in vitro magnetic hyperthermia of hepatocellular carcinoma and dual imaging of in vivo liver fibrosis.

Prolonged usage of traditional nanomaterials in the biological field has posed several short- and long-term toxicity issues. Over the past few years, smart nanomaterials (SNs) with controlled physical, chemical, and biological features have been synthesized in an effort to allay these challenges. The current study seeks to develop theranostic SNs based on iron oxide to enable simultaneous magnetic hyperthermia and magnetic resonance imaging (MRI), for chronic liver damage like liver fibrosis which is a major risk factor for hepatocellular carcinoma. To accomplish this, superparamagnetic iron oxide nanoparticles (SPIONs) were prepared, coated with a biocompatible and naturally occurring polysaccharide, alginate. The resultant material, ASPIONs were evaluated in terms of physicochemical, magnetic and biological properties. A hydrodynamic diameter of 40 nm and a transverse proton relaxation rate of 117.84 mM-1 s-1 pronounces the use of ASPIONs as an efficient MRI contrast agent. In the presence of alternating current of 300 A, ASPIONs could elevate the temperature to 45 °C or more, with the possibility of hyperthermia based therapeutic approach. Magnetic therapeutic and imaging potential of ASPIONs were further evaluated respectively in vitro and in vivo in HepG2 carcinoma cells and animal models of liver fibrosis, respectively. Finally, to introduce dual imaging capability along with magnetic properties, ASPIONs were conjugated with near infrared (NIR) dye Atto 700 and evaluated its optical imaging efficiency in animal model of liver fibrosis. Histological analysis further confirmed the liver targeting efficacy of the developed SNs for Magnetic theranostics and optical imaging as well as proved its short-term safety, in vivo.

Chemical Shift MRI Monitoring of Chemoembolization Delivery for Hepatocellular Carcinoma: Multicenter Feasibility of Initial Clinical Translation.

Purpose To demonstrate the feasibility of using chemical shift fat-water MRI methods to visualize and measure intrahepatic delivery of ethiodized oil to liver tumors following conventional transarterial chemoembolization (cTACE). Materials and Methods Twenty-eight participants (mean age, 66 years ± 8 [SD]; 22 men) with hepatocellular carcinoma (HCC) treated with cTACE were evaluated with follow-up chemical shift MRI in this Health Insurance Portability and Accountability Act-compliant prospective, institutional review board-approved study. Uptake of ethiodized oil was evaluated at 1-month follow-up chemical shift MRI. Measurements of tumor size (MRI and CT), attenuation and enhancement (CT), fat content percentage, and tumor:normal ratio (MRI) were compared by lesion for responders versus nonresponders, as assessed with modified Response Evaluation Criteria in Solid Tumors and European Association for the Study of the Liver (EASL) criteria. Adverse events and overall survival by the Kaplan-Meier method were secondary end points. Results Focal tumor ethiodized oil retention was 46% (12 of 26 tumors) at 24 hours and 47% (18 of 38 tumors) at 1 month after cTACE. Tumor volume at CT did not differ between EASL-defined responders and nonresponders (P = .06). Tumor ethiodized oil volume measured with chemical shift MRI was statistically significantly higher for EASL-defined nonresponders (P = .02). Doxorubicin dosing (P = .53), presence of focal fat (P = .83), and a combined end point of focal fat and low doxorubicin dosing (P = .97) did not stratify overall survival after cTACE. Conclusion Chemical shift MRI allowed for assessment of tumor delivery of ethiodized oil out to 1 month after cTACE in participants with HCC and demonstrated tumor ethiodized oil volume as a potential tool for stratification of tumor response by EASL criteria. Keywords: MRI, Chemical Shift Imaging, CT, Hepatic Chemoembolization, Ethiodized Oil Clinicaltrials.gov registration no.: NCT02173119 Supplemental material is available for this article. © RSNA, 2023.

Thermal ablation of ultrasound and non-contrast computed tomography invisible primary and secondary liver tumors: targeting by selective intra-arterial lipiodol injection.

PURPOSE: To evaluate the technical feasibility and outcomes of thermal ablation following selective intra-arterial lipiodol injection (SIALI) for targeting primary and secondary liver tumors invisible on ultrasound (US) and non-contrast computed tomography (CT). METHODS: This retrospective study included 18 patients with 20 tumors (67% male, mean age 60.8 ± 12.1 years). The 20 tumors included 15 liver metastases and 5 hepatocellular carcinomas. All patients underwent single-session SIALI and subsequent CT-guided thermal ablation. The primary outcome was a technical success, defined as visualization of the tumor after SIALI and successful thermal ablation. Secondary outcomes were local recurrence rate and procedure-related complications. RESULTS: The median tumor size was 1.5 (1-2.5) cm. In addition, SIALI was performed with a median volume of 3 (1-10) mL of lipiodol resulting in intra-tumoral iodized oil accumulation in 19 tumors and negative imprint with iodized oil accumulation of the surrounding liver parenchyma in 1 tumor. The technical success rate was 100%. No local occurrence was observed at a mean follow-up time of 3 ± 2.5 years. CONCLUSION: SIALI to tag liver tumors not visible with US and non-contrast CT before percutaneous ablation is highly feasible and has a high success rate for the treatment of both primary and secondary liver tumors.

Common Bile Duct Obstructed by Lipiodol After Transcater Arterial Chemoembolization for Hepatocellular Carcinoma: A Case Report.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is an effective treatment for hepatocellular carcinoma (HCC), however, the complications of TACE have gradually become a concern of clinicians. Injury to the bile duct has been the focus of many scholars. CASE PRESENTATION: HCC was diagnosed in a 51-year-old female patient, and the first TACE was performed on April 10, 2020. The second TACE was performed on October 18, 2021. After the second TACE, The patient suffered from nausea, jaundice, and body itching. Computed tomography (CT) of the abdomen showed that the lower common bile duct was obviously blocked by the solidified lipiodol accompanied by dilatation of intrahepatic and extrahepatic bile ducts on October 27, 2021. Endoscopic retrograde cholangiopancretography (ERCP) and endoscopic nasobiliary drainage (ENBD) were performed on October 29, 2021. The deposition of lipiodol in the common bile duct was significantly reduced. CONCLUSION: After the transcatheter arterial chemoembolization for hepatocellular carcinoma, we should be on alert for damage to the bile duct, and pay attention to the deposition of lipiodol in the common bile duct.

Hypersensitivity Reactions to Transarterial Chemoembolization with Cisplatin and Ethiodized Oil: A Retrospective Cohort Study.

PURPOSE: To assess the incidence of hypersensitivity reactions (HSRs) and risk factors in patients with unresectable hepatocellular carcinoma (HCC) who have undergone transarterial chemoemblization (TACE) with cisplatin-ethiodized oil emulsion. MATERIALS AND METHODS: Between September 2014 and December 2019, patients with HCC in the authors' institution undergoing TACE with cisplatin-ethiodized oil emulsion were retrospectively reviewed. Clinical, laboratory, and imaging data (including age, sex, etiology of HCC, serum bilirubin, albumin, alpha-fetoprotein, prothrombin time, dose of cisplatin, and details of TACE procedure) and data on procedural complications were retrieved from the registry of TACE. The incidence of HSRs was calculated, and variables were compared between the patient groups with and without HSRs. Predictive factors were analyzed using binary logistic regression. RESULTS: A total of 882 TACE procedures were involved in 257 patients with HCC. The median number of TACE procedures performed per patient was 3 (range, 1-23). The median dose of cisplatin per TACE session was 4.58 mg (range, 0.42-21 mg), and the median accumulated dose of cisplatin per patient was 15.42 mg (range, 0.52-125 mg). HSRs were identified in 22 (2.49%) of 882 procedures (17 [6.61%] of 257 patients). The median number of TACE procedures performed in these patients was 2.5 (range, 1-17). The median dose of cisplatin per TACE session was 5.42 mg (range, 0.63-20 mg), and the median accumulated dose of cisplatin per patient was 18.44 mg (range, 3.33-47.99 mg). Upon binary logistic regression analysis, parameters that showed statistically significant and independent association with HSRs included performance of ≥6 TACE procedures (odds ratio, 3.773; P = .012). CONCLUSIONS: Performance of ≥6 TACE procedures was found to be independently associated with the incidence of HSRs. Patients undergoing multiple TACE procedures should be monitored closely for HSRs.

A Review Of Mri Appearances Of Lipiodol In Conventional Tace (Ctace) Treated Hepatocellular Carcinomas.

Background: The global burden of patients affected by chronic liver disease (CLD) has shown a steady rise over the last few decades and is now considered the 11th most frequent cause of death globally. In addition, as the world population is facing increased obesity rates coupled with alcohol consumption, these rates are predicted to continue to rise. The Objective was to assess the appearance of Lipiodol retention upon different MRI sequences with a special focus on non-contrast sequences. Lipiodol Trans-arterial chemoembolization (TACE) has become the standard treatment for unresectable hepatocellular carcinoma (HCC) without vascular invasion. However, data regarding Lipiodol TACE imaging via MRI is limited and results are not familiar to radiologists for regular assessment of treatment response. Methods: After IRB and EC approval, we included all those patients who underwent TACE treatment with Lipiodol and chemotherapeutic agent; having both 4-6-week post-treatment CT and MRI imaging. This criterion was fulfilled by a total of 25 patients. Only lipiodol-containing areas within the lesion were noted for signal intensities on all MRI sequences and labelled as hyperintense, isointense, hypointense and mixed intensity. Data was entered and analyzed by SPSS v27. Frequencies and percentages were calculated for qualitative data. Results: The most sensitive sequence in detecting Lipiodol retention was Fat suppressed T1 imaging sequence, with low signal intensity seen on T1 weighted fat-suppressed sequences in up to 76% of lesions. While on non-fat suppressed T1 weighted images, 60% of Lipiodol retention areas appeared hyperintense. 52% of lesions showed a hypointense appearance on the T2 weighted sequence. A much more variable appearance was seen in Diffusion-weighted imaging sequences demanding cautious interpretation. MR patterns were clearer in patients having more than 50% lipiodol retention on CT and lesion size more than 2 cm. . Conclusion: While MRI is deemed as a reliable and most useful imaging modality for assessing HCC's following lipiodol TACE it requires cautious interpretation with knowledge of variable signal appearance seen on different imaging sequences.

The radiological prognostic factors of transcatheter arterial chemoembolization to hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) is the recommended treatment modality for intermediate stage hepatocellular carcinoma (HCC). The aim of this study was to determine the HCC radiological characteristics associated with prognosis of patients with intermediate stage HCC receiving TACE. Patients with HCC BCLC stage B from January 2005 to December 2009 were collected. According to mRECIST criteria, patients with complete response and partial response were assigned to the objective response (OR) group, while those with stable disease and progressive disease were assigned to the nonobjective response (non-OR) group. Among a total of 128 enrolled patients, there were 66 (51.6%) and 62 (48.4%) patients in the OR group and non-OR group, respectively. The clinical parameters in the two groups were similar, although HCC size was smaller in the OR group. Logistic analysis found combined radiological characteristics including complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush were significant correlated with achievement of OR (odds ratio 2.46, 95% CI 1.08-5.61, P = .032). However, no radiological characteristics had significant strength to predict overall survival. Patients with OR after TACE had significantly longer survival time than those with non-OR. Combined characteristics of complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush had a positive impact on OR in TACE. In patients receiving TACE, those who achieved OR had a better overall survival.

Targeted Multifunctional Nanoplatform for Imaging-Guided Precision Diagnosis and Photothermal/Photodynamic Therapy of Orthotopic Hepatocellular Carcinoma.

Background: Effective theranostic of hepatocellular carcinoma (HCC) in an early-stage is imminently demanded to improve its poor prognosis. Combination of the near-infrared (NIR) photoacoustic imaging (PAI) and fluorescence imaging (FLI) can provide high temporospatial resolution, outstanding optical contrast, and deep penetration and thus is promising for accurate and sensitive HCC diagnosis. Methods: A versatile CXCR4-targeted Indocyanine green (ICG)/Platinum (Pt)-doped polydopamine melanin-mimic nanoparticle (designated ICG/Pt@PDA-CXCR4, referred to as IPP-c) is synthesized as an HCC-specific contrast agent for high-resolution precise diagnostic PAI/FLI and optical imaging-guided targeted photothermal therapy (PTT)/photodynamic therapy (PDT) of orthotopic small hepatocellular carcinoma (SHCC). Results: The multifunctional targeted nanoparticle yields superior HCC specificity, high imaging contrast in both PAI and FLI, good stability, reliable biocompatibility, effective singlet oxygen generation and superior photothermal conversion efficiency (PCE, 58.7%) upon 808-nm laser irradiation. The targeting ability of IPP-c was validated in in vitro experiments on selectively killing the CXCR4-overexpressing HCC cells. Moreover, we test the efficient dual-modal optical precision diagnosis properties of IPP-c via in vivo experiments on targeted particle accumulation in an early-stage SHCC mouse model (tumor diameter about 1.2 mm). Then, under the guidance of real-time optical imaging, effective and mini-invasive PTT/PDT of orthotopic SHCCs were demonstrated without damaging adjacent liver tissues or other major organs. Conclusion: This study presented a multifunctional CXCR4-targeted nanoparticle to conduct effective and mini-invasive phototherapeutics of orthotopic SHCCs via the real-time quantitative guidance by optical imaging, which provided a new perception for building a versatile targeted nanoplatform for phototheranostics of early-stage HCC.

Initiative on Superselective Conventional Transarterial Chemoembolization Results (INSPIRE).

Several publications show that superselective conventional TransArterial ChemoEmbolization (cTACE), meaning cTACE performed selectively with a microcatheter positioned as close as possible to the tumor, improves outcomes, maximizing the anti-tumoral effect and minimizing the collateral damages of the surrounding liver parenchyma. Recent recommendations coming from the European Association for the Study of the Liver (EASL) and European Society of Medical Oncology (ESMO) highlighted that TACE must be used in Hepatocellular Carcinoma (HCC) "selectively targetable" and "accessible to supraselective catheterization." The goal of the manuscript is to better define such population and to standardize superselective cTACE (ss-cTACE) technique. An expert panel with extensive clinical-procedural experience in TACE, have come together in a virtual meeting to generate recommendations and express their consensus. Experts recommend that anytime cTACE is proposed, it should be ss-cTACE, preferably with a 1.5-2.0 Fr microcatheter. Ideally, ss-cTACE should be proposed to patients with less than five lesions and a maximum number of two segments involved, with largest tumor smaller than 5 cm. Angio Cone-Beam Computed Tomography (CBCT) should be used to detect enhancing tumors, tumor feeders and guide tumor targeting. Whole tumor volume should be covered to obtain the best response. Adding peritumoral margins is encouraged but not mandatory. The treatment should involve a water-in-oil emulsion, whose quality is assessable with the "drop test." Additional particulate embolization should be systematically performed, as per definition of cTACE procedure. Non-contrast CBCT or Multi-Detector Computed Tomography (MDCT) combined with angiography has been considered the gold standard for imaging during TACE, and should be used to assess tumor coverage during the procedure. Experts convene that superselectivity decreases incidence of adverse effects and improves tolerance. Experts recommend contrast-enhanced Computed Tomography (CT) as initial imaging on first follow-up after ss-cTACE, and Magnetic Resonance Imaging (MRI) if remaining tumor viability cannot be confidently assessed on CT. If no response is obtained after two ss-cTACE sessions within six months, patient must be considered unsuitable for TACE and proposed for alternative therapy. Patients are best served by multidisciplinary decision-making, and Interventional Radiologists should take an active role in patient selection, treatment allocation, and post-procedural care.

Lu3+-based nanoprobe for virtual non-contrast CT imaging of hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE), the mainstream treatment for hepatocellular carcinoma (HCC), is a method of blocking tumor blood vessels with a mixture of lipiodol and chemotherapeutics. And the contrast-enhanced computed tomography (CT) is the commonly used way for follow-up of HCC after TACE. However, it is noteworthy that when lipiodol deposition plays an embolic effect, it also produces high-density artifacts in CT images. These artifacts usually conceal the enhancement effect of iodine contrast agents. As a result, the residual region is difficult to be visualized. To overcome this obstacle, we developed one kind of Lu3+/Gd3+ doped fluoride nanoprobe modified with Dp-PEG2000 to realize CT/MRI dual-modality imaging of HCC. Compared with lipiodol or ioversol, the obtained PEGylated product LG-PEG demonstrated a greater density value in high keV CT images. In vitro experiments showed the lipiodol artifacts can be removed in virtual non-contrast (VNC) imaging, but the density of ioversol was also removed at the same time. However, the LG-PEG synthesized in this work can still maintain a high density in VNC imaging, which indicates that LG-PEG can exploit its advantages to the full in VNC imaging. Furthermore, LG-PEG successfully exerted tumor enhancement effects in the in vivo VNC images of HCC with lipiodol deposition. In addition, LG-PEG exhibited a strong T2 enhancement effect with low biological toxicity and less side-effect on the main organ and blood. Thus, the LG-PEG reported in this research can serve as an effective and safe VNC contrast agent for HCC imaging after TACE.

Characterization and Prediction of Signal Intensity Changes in Normal Liver Parenchyma on Gadoxetic Acid-enhanced MRI Scans after Liver-directed Radiation Therapy.

Purpose To better characterize and understand the significance of focal liver reaction (FLR) development in a large cohort of patients who underwent gadoxetic acid-enhanced MRI after being treated with radiation therapy (RT) for hepatobiliary tumors. Materials and Methods This retrospective study evaluated 100 patients (median age, 65 years [first and third quartiles, 60-69 years]; 80 men) who underwent RT for hepatocellular carcinoma, bile duct tumors, or liver metastases at Mount Sinai Hospital between March 1, 2018, and February 29, 2020. CT simulation scans were fused to MRI scans obtained 1-6 months and 6-12 months after RT, using the hepatobiliary phase of the MRI. To define FLR volume, two radiation oncologists independently delineated the borders of the hypointensity observed on MRI scans in the liver region where RT was delivered. Biologically effective dose (BED) thresholds for the formation of FLRs were calculated, along with albumin-bilirubin (ALBI) scores and grades, and overall survival. Results Most patients developed FLRs, which decreased in volume over time. Median BED threshold values for FLR development were 63.6 Gy at 1-6 months and 88.7 Gy at 6-12 months. While higher baseline ALBI scores were associated with a lower rate of FLRs, there was a significant association between FLR volume and increase in ALBI score at 1-6 months (P = .048). Twelve- and 24-month survival estimates for the cohort were 81% and 48%, respectively. Histopathologic analysis of seven explanted liver specimens demonstrated findings consistent with radiation-induced liver disease. Conclusion FLRs were a clear measure of liver damage after RT and were associated with the development of liver dysfunction and focal radiation-induced liver disease. Keywords: MRI, Radiation Therapy Supplemental material is available for this article. © RSNA, 2022.

Imaging Diagnosis of Primary Liver Cancer Using Magnetic Resonance Dilated Weighted Imaging and the Treatment Effect of Sorafenib.

Objective: This work explores the application value of dilated weighted imaging (DWI) in the diagnosis of primary liver cancer (PLC) and the effect of sorafenib in the treatment of PLC. Methods: 88 patients with PLC who were treated in The First Affiliated Hospital of Northwest University from March 2019 to March 2021 were selected and randomly rolled into an experimental group and a control group, with 44 cases in each group. Patients in both groups were treated with transcatheter arterial chemoembolization (TACE), and the patients in the experimental group were treated with oral sorafenib on the basis of TACE. The indicators of complications, short-term efficacy (STE), and long-term efficacy (LTE) of the two groups were observed. All patients received DWI and magnetic resonance (MR) plain scan. The diagnostic accuracy and misdiagnosis rate of the two methods in diagnosing the PLC were compared. Results: The accuracy, specificity, and sensitivity of MR plain scan were 68%, 88%, and 89%, respectively, while those of DWI were 96%, 95%, and 94.2%, respectively. It indicated that the accuracy, specificity, and sensitivity of DWI in diagnosing lesions were better than those of MR plain scan, especially the diagnostic accuracy (P < 0.05). The objective response rate (ORR) and disease control rate (DCR) of the STE in the experimental group were 30% and 97%, respectively, and those in the control group were 6% and 54.5%, respectively. The experimental group's mean progression-free survival (mPFS) and mean overall survival (mOS) were 12 and 25 months, respectively, while the control group's were 8 and 19 months, respectively. It was concluded that the mPFS and mOS of patients receiving TACE combined with oral sorafenib were much higher than those receiving TACE only (P < 0.05). Conclusion: DWI and TACE combined with sorafenib had high application value in the diagnosis and treatment of PLC.

A clinical trial of super-stable homogeneous lipiodol-nanoICG formulation-guided precise fluorescent laparoscopic hepatocellular carcinoma resection.

BACKGROUND: Applying traditional fluorescence navigation technologies in hepatocellular carcinoma is severely restricted by high false-positive rates, variable tumor differentiation, and unstable fluorescence performance. RESULTS: In this study, a green, economical and safe nanomedicine formulation technology was developed to construct carrier-free indocyanine green nanoparticles (nanoICG) with a small uniform size and better fluorescent properties without any molecular structure changes compared to the ICG molecule. Subsequently, nanoICG dispersed into lipiodol via a super-stable homogeneous intermixed formulation technology (SHIFT&nanoICG) for transhepatic arterial embolization combined with fluorescent laparoscopic hepatectomy to eliminate the existing shortcomings. A 52-year-old liver cancer patient was recruited for the clinical trial of SHIFT&nanoICG. We demonstrate that SHIFT&nanoICG could accurately identify and mark the lesion with excellent stability, embolism, optical imaging performance, and higher tumor-to-normal tissue ratio, especially in the detection of the microsatellite lesions (0.4 × 0.3 cm), which could not be detected by preoperative imaging, to realize a complete resection of hepatocellular carcinoma under fluorescence laparoscopy in a shorter period (within 2 h) and with less intraoperative blood loss (50 mL). CONCLUSIONS: This simple and effective strategy integrates the diagnosis and treatment of hepatocellular carcinoma, and thus, it has great potential in various clinical applications.

An injectable thermosensitive hydrogel loaded with a theranostic nanoprobe for synergistic chemo-photothermal therapy for multidrug-resistant hepatocellular carcinoma.

Multi-drug resistance (MDR) is a complicated cellular defense mechanism for tumor cells to resist chemotherapy drugs, which is also the main cause of chemotherapy failure. In this study, a local injectable hydrogel delivery system was used to construct an on-demand sustained-release platform with the advantages of chemotherapy, photothermal therapy (PTT), and magnetic resonance imaging (MRI). It could achieve synergistic chemo-photothermal therapy and real-time evaluation of the therapeutic effects (via MRI) for MDR hepatocellular carcinoma (HCC). Furthermore, after a single administration, the prepared hydrogel with a theranostic nanoprobe could release the therapeutic agents on demand for up to 14 d. Firstly, doxorubicin (DOX) and gold-manganese oxide (Au-MnO) nanoparticles (NPs) were incorporated into liposome-based self-assembled micelles, then loaded into the thermosensitive hydrogel (F127) to form DOX@Au-MnO-L NPs/F127 hydrogel (DAML/H). The prepared NP complex showed a spherical morphology with a narrow size distribution. The prepared hydrogel drug delivery system had injectable properties and stable photothermal conversion. Both the DOX@Au-MnO-L NPs and DAML/H showed controlled drug release under near infrared (NIR) laser irradiation. The in vitro MRI studies indicated that the prepared DAML/H had a high relaxation rate (14.38 mM-1 s-1) and good MRI scanning sensitivity conditions. The in vitro and in vivo results suggested the synergistic chemo-photothermal therapy of DAML/H with NIR irradiation (808 nm, 1 W cm-2, 10 min) improved the antitumor efficacy for MDR HCC. The in vivo retention experiment of Au in tumors indicated that the prepared hydrogel drug delivery system (DAML/H) had a good ability to retain Au in the tumor for a long time (at least 14 d). The western blotting results revealed that DAML/H with laser treatment could effectively downregulate P-glycoprotein (P-gp), p53 and antiapoptotic protein (Bcl-2), whereas the expression level of proapoptotic protein (Bax) and caspase-3 were increased. Therefore, DAML/H could serve as a promising synergistic chemo-photothermal therapy for MDR HCC, and a single administration might achieve long-term (14 d), on-demand, sustained-release treatment of tumors.