Background: It is still a challenge to prevent tumor recurrence post radiofrequency ablation (RFA) of medium-to-large hepatocellular carcinomas (HCC). Immunochemotherapy, a combination of immunotherapy with chemotherapy, has demonstrated a great potential in augmenting the treatment efficacy for some malignancies. In this study, we validated the feasibility of using radiofrequency hyperthermia (RFH)-enhanced intratumoral immunochemotherapy of LTX-315 with liposomal doxorubicin for rat orthotopic HCC. Methods: Different groups of luciferase-labeled rat HCC cells and rat orthotopic HCC models were treated by: (1) phosphate buffered saline; (2) RFH; (3) LTX-315; (4) RFH+LTX-315; (5) liposomal doxorubicin; (6) RFH+liposomal doxorubicin; (7) LTX-315+liposomal doxorubicin; and (8) RFH+LTX-315+liposomal doxorubicin. Cell viabilities and apoptosis of different treatment groups were compared. Changes in tumor sizes were quantified by optical and ultrasound imaging, which were confirmed by subsequent histopathology. The potential underlying biological mechanisms of the triple combination treatment (RFH+LTX-315+liposomal doxorubicin) were explored. Results: Flow cytometry and MTS assay showed the highest percentage of apoptotic cells and lowest cell viability in the triple combination treatment group compared with other seven groups (p<0.001). Tumors in this group also presented the most profound decrease in bioluminescence signal intensities and the smallest tumor volumes compared with other seven groups (p<0.001). A significant increase of CD8⁺ T cells, CD8⁺/interferon (IFN)-γ⁺ T cells, CD8⁺/tumor necrosis factor (TNF)-α⁺ T cells, and natural killer cells, and a significant decrease of regulatory T cells were observed in the tumors (p<0.001). Meanwhile, a significantly higher level of Th1-type cytokines in both plasma (interleukin (IL)-2, IL-12, IL-18, IFN-γ) and tumors (IL-2, IL-18, IFN-γ, TNF-α), as well as a significantly lower Th2-type cytokines of IL-4 and IL-10 in plasma and tumor were detected. Conclusions: Intratumoral RFA-associated RFH could enhance the efficacy of immunochemotherapy of LTX-315 with liposomal doxorubicin for HCC, which may provide a new strategy to increase the curative efficacy of thermal ablation for medium-to-large HCC.

PURPOSE: To evaluate the feasibility of radiofrequency (RF)-enhanced vascular gene transduction and expression by using a magnetic resonance (MR) imaging–heating guidewire as an intravascular heating vehicle during MR imaging–guided therapy. MATERIALS AND METHODS: The institutional committee for animal care and use approved the experimental protocol. The study included in vitro evaluation of the use of RF energy to enhance gene transduction and expression in vascular cells, as well as in vivo validation of the feasibility of intravascular MR imaging–guided RF-enhanced vascular gene transduction and expression in pig arteries. For in vitro experiments, approximately 10⁴ vascular smooth muscle cells were seeded in each of four chambers of a cell culture plate. Next, 1 mL of a green fluorescent protein gene (gfp)-bearing lentivirus was added to each chamber. Chamber 4 was heated at approximately 41°C for 15 minutes by using an MR imaging–heating guidewire connected to a custom RF generator. At day 6 after transduction, the four chambers were examined and compared at confocal microscopy to determine the efficiency of gfp transduction and expression. For the in vivo experiments, a lentivirus vector bearing a therapeutic gene, vascular endothelial growth factor 165 (VEGF-165), was transferred by using a gene delivery balloon catheter in 18 femoral-iliac arteries (nine artery pairs) in domestic pigs and Yucatan pigs with atherosclerosis. During gene infusion, one femoral-iliac artery in each pig was heated to approximately 41°C with RF energy transferred via the intravascular MR imaging–heating guidewire, while the contralateral artery was not heated (control condition). At day 6, the 18 arteries were harvested for quantitative Western blot analysis to compare VEGF-165 transduction and expression efficiency between RF-heated and nonheated arterial groups. RESULTS: Confocal microscopy showed gfp expression in chamber 4 that was 293% the level of expression in chamber 1 (49.6% ± 25.8 vs 16.8% ± 8.0). Results of Western blot analysis showed VEGF-165 expression for normal arteries in the RF-heated group that was 300% the level of expression in the nonheated group (70.4 arbitrary units [au] ± 107.1 vs 23.5 au ± 29.8), and, for atherosclerotic arteries in the RF-heated group, 986% the level in the nonheated group (129.2 au ± 100.3 vs 13.1 au ± 4.9). CONCLUSION: Simultaneous monitoring and enhancement of vascular gene delivery and expression is feasible with the MR imaging–heating guidewire. © RSNA, 2005

Background/Objective: Hematoma expansion (HE) predicts poor outcome and is an appealing treatment target in spontaneous intracerebral hemorrhage (ICH). Clinical evidence has shown an association of HE with peripheral white blood cells (WBC) count, but the individual contributions of leukocyte types between literatures are described inconsistently. Our aim was to determine the relationship between admission absolute and differential leukocyte counts and HE by using various growth definitions. Methods: We analyzed spontaneous ICH patients who underwent baseline cranial computed tomography and blood sampling within 6 hours of stroke onset in our institution between September 2013 and August 2018. Hematoma volume was calculated using a semiautomated 3-dimensional reconstruction algorithm. According to commonly used absolute or relative growth definitions (>6 mL, >12.5 mL, or >33%), we defined 5 types of HE. Univariate and multivariable logistic regression models were constructed to evaluated the influence of complete blood count components on HE. The receiver operating characteristic analysis assessed the predictive ability of leukocyte counts for HE. Results: A total of 1066 patients were included, of whom 11% to 21% met the 5 HE definitions. Except using the absolute definition of >12.5 mL growth, both WBC and neutrophil count were independently associated with reduced risk of HE (odds ratio [OR] for 1000 cells increase; OR, 0.92-0.96; all p 0.05). Regardless of the growth definition, admission eosinophil count was directly associated with the risk of HE (OR, 3.64-6.71; all p <0.05), and was the best predictive subtype with the area under the curve 0.64, sensitivity 69.5%, and specificity 58.9% at the optimal cut-off value of 45 cells/uL. Conclusions: Growth definition affects the relationship of HE with leukocyte subtypes counting. Eosinophil count robustly predict HE, and may be a surrogate when using an inflammatory marker to help select acute ICH patients with high expansion risk for hemostasis treatment in clinical trial and practice.

The aim of this study was to develop an interventional optical imaging (OI) technique for intraprocedural guidance of complete tumor ablation. Our study employed four strategies: 1) optimizing experimental protocol of various indocyanine green (ICG) concentrations/detection time windows for ICG-based OI of tumor cells (ICG cells); 2) using the optimized OI to evaluate ablation-heat effect on ICG cells; 3) building the interventional OI system and investigating its sensitivity for differentiating residual viable tumors from nonviable tumors; and 4) preclinically validating its technical feasibility for intraprocedural monitoring of radiofrequency ablations (RFAs) using animal models with orthotopic hepatic tumors. OI signal-to-background ratios (SBRs) among preablation tumors, residual, and ablated tumors were statistically compared and confirmed by subsequent pathology. The optimal dose and detection time window for ICG-based OI were 100 μg/mL at 24 h. Interventional OI displayed significantly higher fluorescence signals of viable ICG cells compared with nonviable ICG cells (189.3 ± 7.6 versus 63.7 ± 5.7 au, P < 0.001). The interventional OI could differentiate three definitive zones of tumor, tumor margin, and normal surrounding liver, demonstrating significantly higher average SBR of residual viable tumors compared to ablated nonviable tumors (2.54 ± 0.31 versus 0.57 ± 0.05, P < 0.001). The innovative interventional OI technique permitted operators to instantly detect residual tumors and thereby guide repeated RFAs, ensuring complete tumor eradication, which was confirmed by ex vivo OI and pathology. In conclusion, we present an interventional oncologic technique, which should revolutionize the current ablation technology, leading to a significant advancement in complete treatment of larger or irregular malignancies. Significance We present an interventional optical imaging–guided oncologic technique. This interventional oncologic technique can differentiate, in vivo, the three definitive zones of tumor and tumor margin as well as normal surrounding liver, which enables differentiation of residual viable tumors from ablated nonviable tumors and thereby pretermit the intraprocedural real-time guidance for complete tumor eradication during a single interventional ablation session. This innovation should revolutionize the current ablation technology, leading to a significant advancement in the complete treatment of larger or irregular malignant lesions not only in the liver but also in other solid organs.