Comparative analysis of glymphatic system alterations in multiple sclerosis and neuromyelitis optica spectrum disorder using MRI indices from diffusion tensor imaging.

OBJECTIVE: The glymphatic system is a glial-based perivascular network that promotes brain metabolic waste clearance. Glymphatic system dysfunction has been observed in both multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), indicating the role of neuroinflammation in the glymphatic system. However, little is known about how the two diseases differently affect the human glymphatic system. The present study aims to evaluate the diffusion MRI-based measures of the glymphatic system by contrasting MS and NMOSD. METHODS: This prospective study included 63 patients with NMOSD (n = 21) and MS (n = 42) who underwent DTI. The fractional volume of extracellular-free water (FW) and an index of diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS) were used as indirect indicators of water diffusivity in the interstitial extracellular and perivenous spaces of white matter, respectively. Age and EDSS scores were adjusted. RESULTS: Using Bayesian hypothesis testing, we show that the present data substantially favor the null model of no differences between MS and NMOSD for the diffusion MRI-based measures of the glymphatic system. The inclusion Bayes factor (BF10) of model-averaged probabilities of the group (MS, NMOSD) was 0.280 for FW and 0.236 for the ALPS index. CONCLUSION: Together, these findings suggest that glymphatic alteration associated with MS and NMOSD might be similar and common as an eventual result, albeit the disease etiologies differ. PRACTITIONER POINTS: Previous literature indicates important glymphatic system alteration in MS and NMOSD. We explore the difference between MS and NMOSD using diffusion MRI-based measures of the glymphatic system. We show support for the null hypothesis of no difference between MS and NMOSD. This suggests that glymphatic alteration associated with MS and NMOSD might be similar and common etiology.

Predicting hematoma expansion in acute spontaneous intracerebral hemorrhage: integrating clinical factors with a multitask deep learning model for non-contrast head CT.

PURPOSE: To predict hematoma growth in intracerebral hemorrhage patients by combining clinical findings with non-contrast CT imaging features analyzed through deep learning. METHODS: Three models were developed to predict hematoma expansion (HE) in 572 patients. We utilized multi-task learning for both hematoma segmentation and prediction of expansion: the Image-to-HE model processed hematoma slices, extracting features and computing a normalized DL score for HE prediction. The Clinical-to-HE model utilized multivariate logistic regression on clinical variables. The Integrated-to-HE model combined image-derived and clinical data. Significant clinical variables were selected using forward selection in logistic regression. The two models incorporating clinical variables were statistically validated. RESULTS: For hematoma detection, the diagnostic performance of the developed multi-task model was excellent (AUC, 0.99). For expansion prediction, three models were evaluated for predicting HE. The Image-to-HE model achieved an accuracy of 67.3%, sensitivity of 81.0%, specificity of 64.0%, and an AUC of 0.76. The Clinical-to-HE model registered an accuracy of 74.8%, sensitivity of 81.0%, specificity of 73.3%, and an AUC of 0.81. The Integrated-to-HE model, merging both image and clinical data, excelled with an accuracy of 81.3%, sensitivity of 76.2%, specificity of 82.6%, and an AUC of 0.83. The Integrated-to-HE model, aligning closest to the diagonal line and indicating the highest level of calibration, showcases superior performance in predicting HE outcomes among the three models. CONCLUSION: The integration of clinical findings with non-contrast CT imaging features analyzed through deep learning showed the potential for improving the prediction of HE in acute spontaneous intracerebral hemorrhage patients.

Added prognostic value of 3D deep learning-derived features from preoperative MRI for adult-type diffuse gliomas.

BACKGROUND: To investigate the prognostic value of spatial features from whole-brain MRI using a three-dimensional (3D) convolutional neural network for adult-type diffuse gliomas. METHODS: In a retrospective, multicenter study, 1925 diffuse glioma patients were enrolled from 5 datasets: SNUH (n = 708), UPenn (n = 425), UCSF (n = 500), TCGA (n = 160), and Severance (n = 132). The SNUH and Severance datasets served as external test sets. Precontrast and postcontrast 3D T1-weighted, T2-weighted, and T2-FLAIR images were processed as multichannel 3D images. A 3D-adapted SE-ResNeXt model was trained to predict overall survival. The prognostic value of the deep learning-based prognostic index (DPI), a spatial feature-derived quantitative score, and established prognostic markers were evaluated using Cox regression. Model evaluation was performed using the concordance index (C-index) and Brier score. RESULTS: The MRI-only median DPI survival prediction model achieved C-indices of 0.709 and 0.677 (BS = 0.142 and 0.215) and survival differences (P < 0.001 and P = 0.002; log-rank test) for the SNUH and Severance datasets, respectively. Multivariate Cox analysis revealed DPI as a significant prognostic factor, independent of clinical and molecular genetic variables: hazard ratio = 0.032 and 0.036 (P < 0.001 and P = 0.004) for the SNUH and Severance datasets, respectively. Multimodal prediction models achieved higher C-indices than models using only clinical and molecular genetic variables: 0.783 vs. 0.774, P = 0.001, SNUH; 0.766 vs. 0.748, P = 0.023, Severance. CONCLUSIONS: The global morphologic feature derived from 3D CNN models using whole-brain MRI has independent prognostic value for diffuse gliomas. Combining clinical, molecular genetic, and imaging data yields the best performance.

Reappraisal of Portal Vein Tumor Thrombosis as a Prognostic Factor for Patients with Hepatocellular Carcinoma.

Background/Aims: : This study aimed to assess whether hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) could have favorable prognoses with proper treatment under selective conditions. Methods: : This retrospective, single-center study involved 1,168 patients diagnosed with HCC between January 2005 and December 2006, before the introduction of sorafenib. Overall survival (OS) was estimated using the Kaplan-Meier method, and the Cox proportional hazards model was used to identify and adjust the variables associated with OS. Results: : In nodular-type HCC, the OS differed significantly according to the presence of PVTT (log-rank p<0.001), and the level of PVTT, not only its presence, was a major independent factor affecting OS. PVTT at the Vp1-3 branch was associated with significantly longer OS than was PVTT at the Vp4 level (hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.04 to 3.21). In multivariate analysis, the OS was further stratified according to the PVTT level and tumor type, representing that nodular HCC without PVTT exhibited the best OS, whereas nodular HCC with Vp4 PVTT (adjusted HR, 2.59; 95% CI, 1.57 to 4.28) showed a poor prognosis similar to that of infiltrative HCC. The PVTT level was consistently correlated with OS in patients treated with transarterial chemoembolization. Nodular HCC without PVTT showed the best prognosis, while nodular HCC with Vp1-3 PVTT also exhibited a favorable OS, although inferior to that without PVTT (adjusted HR, 1.47, 95% CI, 0.92 to 2.36). Conclusions: : Active treatment such as transarterial chemoembolization can be considered for selected PVTT cases. The level of PVTT and type of HCC were independent prognostic factors.

Transarterial Chemoembolization Using Idarubicin Versus Doxorubicin Chemoemulsion in Patients with Hepatocellular Carcinoma (IDADOX): Protocol for a Randomized, Non-inferiority, Double-Blind Trial.

PURPOSE: This study aims to test the hypothesis that idarubicin-based transarterial chemoembolization (IDA-TACE), using one of the most potent chemotherapeutic agents, could yield oncologic outcomes equivalent to or marginally improved over doxorubicin-based TACE (DOX-TACE). MATERIALS AND METHODS: This single-center, prospective, phase II, randomized controlled, non-inferiority, double-blind trial will enroll 128 treatment-naïve patients with HCC (≤ 5 tumors, 1-5 cm in diameter) for conventional TACE. Participants will be randomly assigned (1:1) to either IDA-TACE or DOX-TACE, with stratification by Child-Pugh class. Superselective conventional TACE will be performed using cone-beam CT and small-bore microcatheters. Patient evaluations, including dynamic imaging and blood tests, will occur at 1, 3, and 6 months post-initial treatment. The primary outcome measure is the objective response rate (ORR) according to mRECIST at 6 months. Secondary outcomes include 3-month and 6-month tumor responses, time-to-progression, the incidence of treatment-related serious adverse events within 30 days, and the incidence and severity of any adverse events. STATISTICS: Non-inferiority will be claimed if the upper limit of a one-sided 97.5% confidence interval for the proportion difference (i.e., "6-month ORR of DOX-TACE" - "6-month ORR of IDA-TACE") falls below 0.15 in both intention-to-treat and per-protocol analyses. The proportion difference and its confidence interval will be calculated by the Cochran-Mantel-Haenszel method to obtain a weighted average of stratum-specific proportion differences. EXPECTED GAIN OF KNOWLEDGE: If IDA-TACE demonstrates outcomes comparable to DOX-TACE, this study could provide compelling evidence that various cytotoxic agents yield similar contributions in TACE, considering the minor role of chemotherapeutic agents in TACE. TRIAL REGISTRATION: ClinicalTrials.gov ( https://clinicaltrials.gov/ ). Identifier: NCT06114082. World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) ( https://trialsearch.who.int/Default.aspx ). Identifier: KCT0008166.

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.

Use of doxorubicin-eluting bead transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein invasion: a prospective study.

Background/Aim: To evaluate the applicability of transarterial chemoembolization (TACE) treatment with doxorubicin drug-eluting beads (DEBs) in advanced hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). Methods: This prospective study was approved by the institutional review board and informed consent was obtained from all participants. A total of 30 HCC patients with PVI received DEB-TACE between 2015 and 2018. The following parameters were evaluated: complications during DEB-TACE, abdominal pain, fever, and laboratory outcomes, including liver function change. Overall survival (OS), time to progression (TTP), and adverse events were also analyzed and assessed. Results: DEBs measuring 100-300 µm in diameter were loaded with doxorubicin (150 mg per procedure). There were no complications during DEB-TACE and no significant differences in the levels of prothrombin time, serum albumin, or total bilirubin at follow-up compared to baseline. The median TTP was 102 days (95% confidence interval [CI], 42-207 days) and the median OS was 216 days (95% CI, 160-336 days). Three patients (10%) had severe adverse reactions, including transient acute cholangitis (n=1), cerebellar infarction (n=1), and pulmonary embolism (n=1), but no treatment-related death occurred. Conclusions: DEB-TACE may be a therapeutic option for advanced HCC patients with PVI.

Prognostication and risk factor stratification for survival of patients with hepatocellular carcinoma: a nationwide big data analysis.

This study was conducted to identify risk factors affecting overall survival (OS) and provide prognostication for patients with hepatocellular carcinoma (HCC) using nationwide big data. Between January 2008 and December 2014, 10,573 adult patients with new HCC were registered in a nationwide database. Among them, 6830 patients without missing data were analyzed to construct a prognostication system. A validation cohort of 4580 patients was obtained from a tertiary hospital. All patients were assumed to have received the best treatment. A conditional inference tree analysis was performed to establish a prognostic system. The C-index and calibration plot for 5-year survival were estimated for validation. As a result, the tumor burden (TB) grade was the most significant factor in determining OS, and the cutoff was TB3 (TB1‒3 versus TB4). The patients were ultimately divided into 13 prognosis groups. The C-indexes were 0.714 and 0.737 (95% confidence interval, 0.733-0.742) in the nationwide (derivation) and hospital (validation) cohorts, respectively. In the calibration plot, the 5-year survival of the validation cohort largely matched the 45-degree line. In conclusion, the proposed prognostication system with a simple tree structure enabled the detailed stratification of patient prognosis and visualized the strata of risk factors affecting OS.

Transarterial chemoembolization as an alternative to radioembolization is associated with earlier tumor recurrence than in radioembolization-eligible patients.

Introduction: Although transarterial radioembolization (TARE) using yttrium-90 (90Y) is a treatment option for large hepatocellular carcinoma (HCC), a fraction of patients are ineligible for TARE due to high lung shunt fraction (LSF). Methods: We evaluated if treatment with transarterial chemoembolization (TACE), owing to TARE ineligibility was associated with early HCC progression. Consecutive patients with HCC who were initially TARE candidates were included. Patients with vascular invasion or metastasis were excluded. Primary endpoints were time-to-progression (TTP) and overall survival (OS). The secondary endpoint was objective response rate. Results: In total, 175 patients were included: 144 underwent TARE (TARE-eligible group) and 31 underwent TACE due to high LSF (TARE-ineligible group). This latter group had larger tumors (13.8 cm vs. 7.8 cm, P<0.001) and higher MoRAL scores (1,385.8 vs. 413.3, P=0.002) than the TARE-eligible group. After balancing baseline characteristics with an inverse probability of treatment weighting (IPTW), the TARE-ineligible group showed shorter TTP [adjusted hazard ratio (aHR)=2.16, 95% confidence interval (CI)=1.14-4.07, P=0.02] and OS (aHR=1.80, 95% CI=0.85-3.80, P=0.12), although the latter was not statistically significant. The TARE-ineligible group had a significantly lower objective response rate than the TARE-eligible group (9.7% vs. 56.9%, P<0.001). Conclusion: TARE-ineligible patients had larger tumors and higher MoRAL scores than TARE-eligible patients. Treatment with TACE, owing to high LSF, was associated with a shorter TTP even after balancing tumor size and MoRAL scores.

Pre-Attentional Effects on Global Precedence Processing in Children with Autism Spectrum Disorder and Those with Typical Development on a Tablet-Based Modified Navon's Paradigm Task.

This study aimed to characterize the pre-attentional effects on global precedence processing in children with autism spectrum disorder (ASD) and those with typical development (TD). A sample of 17 participants, comprising eight children with ASD and nine TD children, were recruited for the study. A tablet-based assessment utilizing a global and local visual processing paradigm task was developed to investigate the participant's abilities. The task consisted of verbal instructions to locate and touch either a global or local figure, presented in five conditions: neutral, congruent, and incongruent. The percentage of correct answers and reaction time (RT) for each task were measured and analyzed statistically. Results revealed that children with ASD exhibited statistically significant differences in both the percentage of correct scores and RT among various conditions, while TD children displayed differences in RT but not in the percentage of correct answers. These findings suggest that conflicting processes affect both behavioral and cognitive processes in children with ASD, and that cognitive effort is still involved for children with TD, but does not affect behavioral processes. In children with ASD, the RT was the shortest in the congruent (report local figure) condition; in children with TD, the RT was the shortest in the congruent (report global figure) condition. This implies that children with TD exhibit a pre-attentive effect on global precedence processing, while children with ASD do not. These visual-processing-function characteristics may aid in screening for visual perception problems in children with ASD.

Modified design of x-ray protective clothing to enhance radiation protection for interventional radiologists.

BACKGROUND: In interventional radiology procedures, the operator typically stands on the right side of the patient's right thigh to manipulate devices through the femoral sheath. Because the standard x-ray protective clothing is designed as sleeveless and scatter radiations from the patient are mainly incident from the left-anterior direction to the operator, the arm hole of the clothing may be a significant unprotected area, contributing to an increase in the operator's organ doses and effective dose. PURPOSE: This study aimed to compare the organ doses and effective dose received by the interventional radiologist when wearing the standard x-ray protective clothing and when wearing the modified clothing with an additional shoulder guard. METHODS: The experimental setup aimed to simulate actual clinical practice in interventional radiology. The patient phantom was located at the beam center to generate scatter radiation. An adult female anthropomorphic phantom loaded with 126 nanoDots (Landauer Inc., Glenwood, IL) was used to measure organ and effective doses to the operator. The standard wrap-around type x-ray protective clothing offered 0.25-mm lead-equivalent protection, and the frontal overlap area offered 0.50-mm lead-equivalent protection. The shoulder guard was custom-made with a material providing x-ray protection equivalent to lead of 0.50 mm thickness. The organ and effective doses were compared between the operator wearing the standard protective clothing and the one wearing the modified clothing with a shoulder guard. RESULTS: After adding the shoulder guard, doses to the lungs, bone marrow, and esophagus decreased by 81.9%, 58.6%, and 58.7%, respectively, and the effective dose to the operator decreased by 47.7%. CONCLUSIONS: Widespread use of modified x-ray protective clothing with shoulder guards can significantly decrease the overall occupational radiation risk in interventional radiology.

Association of Blood Mercury Level with Liver Enzymes in Korean Adults: An Analysis of 2015-2017 Korean National Environmental Health Survey.

Increased liver enzymes as a result of exposure to mercury and their toxic effects are not well understood in Korea at the population level. The effect of blood mercury concentration on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was evaluated after adjusting for sex, age, obesity, alcohol consumption habit, smoking, and exercise parameters in 3712 adults. The risk of abnormal liver function was measured using a multiple logistic regression analysis. Blood mercury concentration was divided into quartiles, and liver enzyme levels were compared for each quartile. ALT and AST levels were 10-20% higher in the second, third, and fourth quartiles compared to the first quartile. The risk of liver dysfunction or elevated liver enzymes was significantly higher in the second, third, and fourth quartiles than in the first quartile. As blood mercury levels increased, liver enzymes and mercury-induced hepatotoxicity increased. The increase in liver enzymes caused by mercury was more pronounced in the low-mercury concentration range. To reduce the long-standing problem of abnormal liver enzymes and liver function in Korea and other similar settings, it is important to decrease exposure to mercury through effective implementation of specific health and environmental strategies.

Hepatocellular Carcinoma Supplied by the Inferior Phrenic Artery or Cystic Artery: Anatomic and Technical Considerations.

Intra-arterial treatment has been identified as one of the mainstays in the management of unresectable hepatocellular carcinoma. A thorough knowledge of tumor arterial supply enables selective therapy, which improves both safety and efficacy. The inferior phrenic artery (IPA) is the most common extrahepatic collateral artery that feeds hepatocellular carcinoma. The bilateral IPAs are known to have a specific vascular anatomy. A systemic-to-pulmonary shunt and a gastric branch from the IPAs may be present and should not be confused with tumor blush. The supraceliac aorta and celiac trunk are the common origin sites of the IPAs, and their orifice may be compressed by the diaphragm. Various techniques and catheters are used for catheterization of the IPAs, depending on their origin sites. Because the IPA is normally connected with the intercostal, internal mammary, retroperitoneal, and hepatic arteries, its hemodynamics may be altered when its orifice is occluded. In general, superselective chemoembolization via the target branch of the IPA is safe and effective. When a systemic-to-pulmonary shunt from the IPA is adequately embolized with coils or particles, radioembolization through the IPA can be performed safely in most cases. The cystic artery branches into deep and superficial cystic arteries; deep cystic arteries often supply tumors near the gallbladder. Chemoembolization through the cystic artery is relatively safe, with transient embolic materials. Radioembolization through the cystic artery has been recently tried, with acceptable efficacy and toxicity results, but it requires further investigation. ©RSNA, 2022.

Ideal Size Range for Embolic Agents in Interventional Oncology Experiments Involving Rat Models of Hepatocellular Carcinoma.

PURPOSE: To optimize future translational research, this study aimed to determine the ideal range of sizes for embolic agents in interventional oncology experiments utilizing rat models of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty-five male Sprague-Dawley rats were divided into 2 groups to evaluate the distribution of microparticles and tumor response rates. After implanting hepatoma cells into the rodent liver, fluorescent microparticles of sizes ranging from 5 to 35 µm were administered via the hepatic artery. In the first group, the distribution of microparticles was evaluated in hepatoma-free rats, and the tumor necrosis rates following administration of a predetermined aliquot of microparticles (0.4 mL) were measured in tumor-bearing rats. Thereafter, the 3 microparticle sizes associated with the best tumor response rates were chosen for analysis of the tumor necrosis rates following hepatic artery embolization until angiographic stasis is achieved in the second group. RESULTS: The tendency for microparticles to distribute in nontarget organs increased as the microparticle size decreased below 15 µm. Tumor necrosis rates tended to be higher in rats treated with 15-19-µm microparticles than in those treated with 19-24-µm or 19-24-µm microparticles. The in-group deviation of the tumor necrosis rates was highest for microparticle sizes of 19-24 and 25-35 µm, which implies the proximal embolization of the hepatic artery for larger microparticle sizes. However, there was no statistical significance among the 3 groups (P = .095). CONCLUSIONS: The 15-19-µm embolic agents were the most favorable for causing tumor necrosis without nontarget toxicity in the transarterial treatments of rat HCC models.

Effect of Atorvastatin on Serial Changes in Coronary Physiology and Plaque Parameters.

Background: The effects of statin on coronary physiology have not been well evaluated. Objectives: The authors performed this prospective study to investigate changes in coronary flow indexes and plaque parameters, and their associations with atorvastatin therapy in patients with coronary artery disease (CAD). Methods: Ninety-five patients with intermediate CAD who received atorvastatin therapy underwent comprehensive physiological assessments with fractional flow reserve (FFR), coronary flow reserve, index of microcirculatory resistance, and intravascular ultrasound at the index procedure, and underwent the same evaluations at 12-month follow-up. Optimal low-density lipoprotein cholesterol (LDL-C) was defined as LDL-C <70 mg/dL or ≥50% reduction from the baseline. The primary endpoint was a change in the FFR. Results: Baseline FFR, minimal lumen area, and percent atheroma volume (PAV) were 0.88 ± 0.05, 3.87 ± 1.28, 55.92 ± 7.30, respectively. During 12 months, the percent change in LDL-C was -33.2%, whereas FFR was unchanged (0.87 ± 0.06 at 12 months; P = 0.694). Vessel area, lumen area, and PAV were significantly decreased (all P values <0.05). The achieved LDL-C level and the change of PAV showed significant inverse correlations with the change in FFR. In patients with optimally modified LDL-C, the FFR had increased (0.87 ± 0.06 vs 0.89 ± 0.07; P = 0.014) and the PAV decreased (56.81 ± 6.44% vs 55.18 ± 8.19%; P = 0.031), whereas in all other patients, the FFR had decreased (0.88 ± 0.05 vs 0.86 ± 0.06; P = 0.025) and the PAV remained unchanged. Conclusions: In patients with CAD, atorvastatin did not change FFR despite a decrease in the PAV. However, in patients who achieved the optimal LDL-C target level with atorvastatin, the FFR had significantly increased with decrease of the PAV. (Effect of Atorvastatin on Fractional Flow Reserve in Coronary Artery Disease [FORTE]; NCT01946815).

Drug delivery in transarterial chemoembolization of hepatocellular carcinoma: Ex vivo evaluation using transparent tissue imaging.

In this study, we elucidated for the first time the role of anti-cancer drugs in transarterial chemoembolization (TACE) via direct visualization of the spatial distribution of drugs with respect to blood vessels in intact transparent hepatocellular carcinoma (HCC) tissues. To date, precise estimation of drug penetration into tumors using thin 3D tissue sections has been challenging. This study utilized the tissue optical clearing technique to resolve the lack of tissue clarity, thereby enabling deep tissue imaging for the quantitative assessment of drug delivery following TACE. We compared the drug delivery effect, time-dependent embolic effect, and immunogenic response following conventional TACE (cTACE), drug-eluting embolic TACE (DEE-TACE), and transarterial embolization (TAE) in a rat model of HCC. After each treatment, three-dimensional drug delivery was quantitatively evaluated via the transparent liver tumor imaging, and time-dependent tumor necrosis was analyzed by serial tumor harvesting and histological staining. The results showed that chemotherapeutic agents travel only short distances after cTACE (∼80µm) and DEE-TACE (∼110µm), whereas necrosis occurs extensively within 24 h of treatment (85.3-97.2% of tumor cells). In addition, the percentages of CD4 and IL-17+ CD4 T cells increased significantly following treatment; however, drug-loading did not appear to affect the immune response following TACE. In conclusion, transarterially delivered chemotherapeutic agents appeared to exert a limited role, owing to the rapid and overwhelming effect of embolization. STATEMENT OF SIGNIFICANCE: TACE has been widely used for the treatment of HCC, especially for unresectable intermediate and advanced HCCs. Drug use in TACE is expected to provide patients with synergistic therapeutic benefits with the effect of embolic agents; however, the role of chemotherapeutic agents in TACE remains controversial. This study quantitatively verified that chemotherapeutic agents travel only short distances after TACE, while necrosis occurs extensively within 24h, and drug loading does not significantly affect immune responses following TACE. Three-dimensional imaging of intact transparent HCC can contribute to a better understanding of drug delivery mechanisms associated with TACE and also reveal that drug use in TACE may need to be reconsidered and limited to situations when embolization is expected to be insufficient.