High-resolution extracellular pH imaging of liver cancer with multiparametric MR using Deep Image Prior.

Noninvasive extracellular pH (pHe ) mapping with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) using MR spectroscopic imaging (MRSI) has been demonstrated on 3T clinical MR scanners at 8 × 8 × 10 $$ \times 8\times 10 $$ mm3 spatial resolution and applied to study various liver cancer treatments. Although pHe imaging at higher resolution can be achieved by extending the acquisition time, a postprocessing method to increase the resolution is preferable, to minimize the duration spent by the subject in the MR scanner. In this work, we propose to improve the spatial resolution of pHe mapping with BIRDS by incorporating anatomical information in the form of multiparametric MRI and using an unsupervised deep-learning technique, Deep Image Prior (DIP). Specifically, we used high-resolution T 1 $$ {\mathrm{T}}_1 $$ , T 2 $$ {\mathrm{T}}_2 $$ , and diffusion-weighted imaging (DWI) MR images of rabbits with VX2 liver tumors as inputs to a U-Net architecture to provide anatomical information. U-Net parameters were optimized to minimize the difference between the output super-resolution image and the experimentally acquired low-resolution pHe image using the mean-absolute error. In this way, the super-resolution pHe image would be consistent with both anatomical MR images and the low-resolution pHe measurement from the scanner. The method was developed based on data from 49 rabbits implanted with VX2 liver tumors. For evaluation, we also acquired high-resolution pHe images from two rabbits, which were used as ground truth. The results indicate a good match between the spatial characteristics of the super-resolution images and the high-resolution ground truth, supported by the low pixelwise absolute error.

Effect of Incomplete Cryoablation and Matrix Metalloproteinase Inhibition on Intratumoral CD8+ T-Cell Infiltration in Murine Hepatocellular Carcinoma.

Background Image-guided tumor ablation is the first-line therapy for early-stage hepatocellular carcinoma (HCC), with ongoing investigations into its combination with immunotherapies. Matrix metalloproteinase (MMP) inhibition demonstrates immunomodulatory potential and reduces HCC tumor growth when combined with ablative treatment. Purpose To evaluate the effect of incomplete cryoablation with or without MMP inhibition on the local immune response in residual tumors in a murine HCC model. Materials and Methods Sixty 8- to 10-week-old female BALB/c mice underwent HCC induction with use of orthotopic implantation of syngeneic Tib-75 cells. After 7 days, mice with a single lesion were randomized into treatment groups: (a) no treatment, (b) MMP inhibitor, (c) incomplete cryoablation, and (d) incomplete cryoablation and MMP inhibitor. Macrophage and T-cell subsets were assessed in tissue samples with use of immunohistochemistry and immunofluorescence (cell averages calculated using five 1-µm2 fields of view [FOVs]). C-X-C motif chemokine receptor type 3 (CXCR3)- and interferon γ (IFNγ)-positive T cells were assessed using flow cytometry. Groups were compared using unpaired Student t tests, one-way analysis of variance with Tukey correction, and the Kruskal-Wallis test with Dunn correction. Results Mice treated with incomplete cryoablation (n = 6) showed greater infiltration of CD206+ tumor-associated macrophages (mean, 1.52 cells per FOV vs 0.64 cells per FOV; P = .03) and MMP9-expressing cells (mean, 0.89 cells per FOV vs 0.11 cells per FOV; P = .03) compared with untreated controls (n = 6). Incomplete cryoablation with MMP inhibition (n = 6) versus without (n = 6) led to greater CD8+ T-cell (mean, 15.8% vs 8.29%; P = .04), CXCR3+CD8+ T-cell (mean, 11.64% vs 8.47%; P = .004), and IFNγ+CD8+ T-cell infiltration (mean, 11.58% vs 5.18%; P = .02). Conclusion In a mouse model of HCC, incomplete cryoablation and systemic MMP inhibition showed increased cytotoxic CD8+ T-cell infiltration into the residual tumor compared with either treatment alone. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Gemmete in this issue.

Protrieve sheath utilization for capturing supra-filter thrombus during a retrieval of thrombosed and embedded IVC filter.

BACKGROUND: Inferior vena cava (IVC) filters, while effective in preventing pulmonary embolism, can increase the risk of IVC thrombosis. IVC filter (IVCF) thrombosis can result from emboli getting trapped within the filter, extension of deep vein thrombosis (DVT), or the device's inherent thrombogenicity causing in situ thrombosis. This condition can cause noticeable clinical symptoms and complicate the removal of the filter due to the potential for thromboembolism, often resulting in temporary filters remaining unextracted. This case report highlights a novel approach employed to mitigate the risk of thromboembolism during the procedure by capturing mobilized thrombus proximally to the entrapped IVCF. CASE PRESENTATION: A 54-year-old woman with a complex medical history including cerebral palsy, Crohn's disease, and transfusion-dependent iron-deficiency anemia experienced a pulmonary embolism. Due to failed anticoagulation therapy resulting in gastrointestinal bleeding and high transfusion requirements, she underwent placement of an IVCF as a preventive measure against recurrent pulmonary embolism. Three years later, the patient presented with lower extremity swelling and a sudden decline in hemoglobin levels. Diagnostic imaging revealed adherent nonocclusive thrombus within and above the indwelling IVCF. Utilizing the novel Protrieve sheath with the self-expandable Nitinol funnel, successful endovascular removal of the embedded IVCF and adherent thrombus was performed, while mitigating the risk of intraprocedural pulmonary embolism. CONCLUSIONS: The successful intraprocedural trapping and removal of mobilized thrombus from the IVCF removal was achieved using the Protrieve sheath and Nitinol funnel. This approach provides a promising solution to reduce the risk of embolization during the removal of thrombosed IVCFs, potentially outweighing the complications associated with filter removal.

Hepatic Hypertrophy in Normal and Cirrhotic Livers Following Portal Vein Embolization: Comparative Assessment of 2 Different Embolic Regimens in a Large Animal Model.

PURPOSE: To compare the mechanistic effects and hypertrophy outcomes using 2 different portal vein embolization (PVE) regimens in normal and cirrhotic livers in a large animal model. METHODS AND MATERIALS: The Institutional Animal Care and Use Committee approved all experiments conducted in this study. Fourteen female Yorkshire pigs were separated into a cirrhotic group (CG, n = 7) and non-cirrhotic group (NCG, n = 7) and further subgrouped into those using microspheres and coils (MC, n = 3) or n-butyl cyanoacrylate (nBCA, n = 3) and their corresponding controls (each n = 1). A 3:1 ethiodized oil and ethanol mixture was administered intra-arterially in the CG to induce cirrhosis 4 weeks before PVE. Animals underwent baseline computed tomography (CT), PVE including pre-PVE and post-PVE pressure measurements, and CT imaging at 2 and 4 weeks after PVE. Immunofluorescence stainings for CD3, CD16, Ki-67, and caspase 3 were performed to assess immune cell infiltration, hepatocyte proliferation, and apoptosis. Statistical significance was tested using the Student's t test. RESULTS: Four weeks after PVE, the percentage of future liver remnant (FLR%) increased by 18.8% (standard deviation [SD], 3.6%) vs 10.9% (SD, 0.95%; P < .01) in the NCG vs CG. The baseline percentage of standardized future liver remnant (sFLR%) for the controls were 41.6% for CG vs 43.6% for NCG. Based on the embolic agents used, the sFLR% two weeks after PVE was 58.4% (SD, 3.7%) and 52.2% (SD, 0.9%) (P < .01) for MC and 46.0% (SD, 2.2%) and 47.2% (SD, 0.4%) for nBCA in the NCG and CG, respectively. Meanwhile, the sFLR% 4 weeks after PVE was 60.5% (SD, 3.9%) and 54.9% (SD, 0.8%) (P < .01) and 60.4% (SD, 3.5%) and 54.2% (SD, 0.95%) (P < .01), respectively. Ki-67 signal intensity increased in the embolized lobe in both CG and NCG (P < .01). CONCLUSIONS: This preclinical study demonstrated that MC could be the preferred embolic of choice compared to nBCA when a substantial and rapid FLR increase is needed for resection, in both cirrhotic and non-cirrhotic livers.

Non-Invasive Imaging Biomarkers to Predict the Hepatopulmonary Shunt Fraction Before Transarterial Radioembolization in Patients with Hepatocellular Carcinoma.

Purpose: To identify disease-specific profiles comprising patient characteristics and imaging biomarkers on contrast-enhanced (CE)-computed tomography (CT) that enable the non-invasive prediction of the hepatopulmonary shunt fraction (HPSF) in patients with hepatocellular carcinoma (HCC) before resin-based transarterial radioembolization (TARE). Patients and Methods: This institutional review board-approved (EA2/071/19) retrospective study included 56 patients with HCC recommended for TARE. All patients received tri-phasic CE-CT within 6 weeks prior to an angiographic TARE evaluation study using technetium-99m macroaggregated albumin. Imaging biomarkers representative of tumor extent, morphology, and perfusion, as well as disease-specific clinical parameters, were used to perform data-driven variable selection with backward elimination to generate multivariable linear regression models predictive of HPSF. Results were used to create clinically applicable risk scores for patients scheduled for TARE. Additionally, Cox regression was used to identify independent risk factors for poor overall survival (OS). Results: Mean HPSF was 13.11% ± 7.6% (range: 2.8- 35.97%). Index tumor diameter (p = 0.014) or volume (p = 0.034) in combination with index tumor non-rim arterial phase enhancement (APHE) (p < 0.001) and washout (p < 0.001) were identified as significant non-invasive predictors of HPSF on CE-CT. Specifically, the prediction models revealed that the HPSF increased with index lesion diameter or volume and showed higher HPSF if non-rim APHE was present. In contrast, index tumor washout was associated with decreased HPSF levels. Independent risk factors of poorer OS were radiogenomic venous invasion and ascites at baseline. Conclusion: The featured prediction models can be used for the initial non-invasive estimation of HPSF in patients with HCC before TARE to assist in clinical treatment evaluation while potentially sparing ineligible patients from the angiographic shunt evaluation study.

Experimental VX2 Rabbit Liver Tumor Model in Carbon Tetrachloride-Induced Cirrhosis of the Liver.

Liver cirrhosis is a major underlying factor in the development of hepatocellular carcinoma. Currently, there is an unmet need for midsize experimental vertebrate models that would offer reproducible implantable liver tumors in a cirrhotic liver background. This study establishes a protocol for a syngeneic rabbit model of VX2 liver cancer with underlying liver cirrhosis induced using carbon tetrachloride (CCl4). Male New Zealand white rabbits (n = 3) received CCl4 by intragastric administration once weekly. Concentrations started at 5% v/v CCl4 dissolved in olive oil. CCl4 dosing was progressively increased every week by 2.5% v/v increments for the duration of treatment (16 weeks total). VX2 tumors were then orthotopically implanted into the left hepatic lobe and allowed to grow for 3 weeks. Cross-sectional imaging confirmed the presence of hepatic tumors. Gross and histopathological evaluations showed reproducible tumor growth in the presence of liver cirrhosis in all animals.