Stress Conditions Induced by Locoregional Therapies Stimulate Enrichment and Proliferation of Liver Cancer Stem Cells

PurposeThis study tested the hypothesis that stress conditions that simulated percutaneous thermal ablation (PTA), transarterial embolization (TAE), or transarterial chemoembolization stimulated enrichment of hepatocellular carcinoma (HCC) cancer stem cells (hCSCs) and that hCSC inhibitors can suppress this effect.Materials and MethodsHuman HCC cell lines HepG2 and PLC/PRF/5 were subjected to a 46.5°C heat bath for 10 minutes or to 1% hypoxia for 72 hours without fetal bovine serum and with or without doxorubicin. Cells were then treated with a β-catenin inhibitor (FH535 or XAV939), a PI3 kinase inhibitor (Ly294002), or niclosamide, a US Food and Drug Administration-approved antihelminthic drug that acts as a mitochondrial decoupler and mixed inhibitor. Surviving cells were analyzed for hCSC markers by flow cytometry, for stemness by colony-forming assay or sphere-forming assay, and for proliferative capacity by MTT assay (where MTT is 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide). Expression of proteins related to CSC renewal and proliferation were analyzed by immunoblotting and immunostaining.ResultsConditions that simulated PTA, TAE, and transarterial chemoembolization resulted in an enrichment of cells bearing hCSC markers (CD133, CD44, and EpCAM). Cells surviving heat stress exhibited higher colony- or sphere-forming capacity and a greater proliferative state. These effects could be suppressed by niclosamide and inhibitors of β-catenin and PI3 kinase.ConclusionsStress conditions induced by locoregional therapies stimulated hCSC enrichment and proliferation, which could be suppressed by niclosamide and inhibitors of pathways important for hCSC renewal. Future studies will determine whether combining locoregional therapies with adjuvant hCSC inhibitors reduces HCC recurrence.     

Screening of Polymer-Based Drug Delivery Vehicles Targeting Folate Receptors in Triple-Negative Breast Cancer

PurposeTo compare cellular uptake and cytotoxicity of fluorescein (FL)-labeled polyethylene glycols (PEGs) carrying 2 folate groups (targeted delivery vehicles [TDVs]) to non-PEGylated molecules with 1 or 2 folate groups.Materials and MethodsThree PEGylated TDVs and 2 non-PEGylated folic acid (FA)–fluorescein (FL) conjugates (FA-FL and FA-FL-FA) were synthesized. Two triple-negative breast cancer cell lines (MDA-MB-231and MDA-MB-468) were cultured to 70% confluency and incubated for 2 h in a folate-depleted medium. Folate receptor (FR) expression was confirmed by immunocytochemistry. Cellular uptake and cytotoxicity of compounds were measured by flow cytometry. Intracellular localization was confirmed using confocal microscopy.ResultsMDA-MB-231 demonstrated 40% more FR staining than MD-MB-468. Intracellular localization of the 2 non-PEGylated molecules (FA-FL and FA-FL-FA) and the 3 PEGylated TDVs was confirmed with confocal microscopy. Cellular uptake was independent of concentration for FA-FL, but there was 26.8% more cytotoxicity at 30 μg/mL compared with no treatment (P ≤ .05). Uptake was > 90% for FA-FL-FA at 10 μg/mL and 30 μg/mL without significant cytotoxicity (P ≤ .005). Cellular uptake was > 80% for all TDVs. The molecule containing monodispersed PEG with M_n = 1,000 g/mol had the highest uptake in both cell lines without cytotoxicity. Maximum toxicity was demonstrated by the molecule containing PEG_2,000 only at the highest dose of 30 μg/mL (8.66% ± 3.94% cytotoxicity; cut-off was 20%).ConclusionsThe molecule containing monodispersed PEG with M_n = 1,000 g/mol and 2 FA targeting groups demonstrated better targetability and cellular uptake as a TDV.     

Evaluation of Venous Stenosis Angioplasty in a Murine Arteriovenous Fistula Model

PurposeTo develop a clinically relevant model of percutaneous transluminal angioplasty (PTA) of venous stenosis in mice with arteriovenous fistula (AVF); to test the hypothesis that there is increased wall shear stress (WSS) after PTA; and to histologically characterize the vessels.Materials and MethodsThirteen C57BL/6J male mice, 6–8 weeks old, underwent partial nephrectomy to create chronic kidney disease. Twenty-eight days later, an AVF was created from the right external jugular vein to the left carotid artery. Fourteen days later, an angioplasty or sham procedure was performed, and the mice were sacrificed 14 days later for histologic evaluation to identify the cells contributing to the vascular remodeling (α-SMA, FSP-1, CD31, and CD68), proliferation (Ki-67), cell death (TUNEL), and hypoxia staining (HIF-1α). Histomorphometric analysis was performed to assess lumen area, neointima+media area, and cellular density. Ultrasound was performed weekly after creation of the AVF.ResultsVenous stenosis occurred 14 days after the creation of an AVF. PTA-treated vessels had significantly higher WSS; average peak systolic velocity, with increased lumen vessel area; and decreased neointima + media area compared to sham controls. There was a significant decrease in the staining of smooth muscle cells, fibroblasts, macrophages, HIF-1α, proliferation, and apoptosis and an increase in CD31-(+) cells.ConclusionsA clinically relevant model of PTA of venous stenosis in mice was created. PTA-treated vessels had increased lumen vessel area and WSS. The alterations in tissue markers of vascular remodeling, tissue hypoxia, proliferation, and cell death may be implications for future design of drug and device development.     

Treatment of Hepatocellular Carcinoma by Multimodal In Situ Vaccination Using Cryoablation and a Plant Virus Immunostimulant

PurposeTo test the hypothesis that cryoablation combined with intratumoral immunomodulating nanoparticles from cowpea mosaic virus (CPMV) as an in situ vaccination approach induces systemic antitumoral immunity in a murine model of hepatocellular carcinoma (HCC).Materials and MethodsMice with bilateral, subcutaneous RIL-175 cell–derived HCCs were randomized to 4 groups: (a) phosphate-buffered saline (control), (b) cryoablation only (Cryo), (c) CPMV-treated only (CPMV), and (d) cryoablation plus CPMV-treated (Cryo + CPMV) (N = 11–14 per group). Intratumoral CPMV was administered every 3 days for 4 doses, with cryoablation performed on the third day. Contralateral tumors were monitored. Tumor growth and systemic chemokine/cytokine levels were measured. A subset of tumors and spleens were harvested for immunohistochemistry (IHC) and flow cytometry. One- or 2-way analysis of variance was performed for statistical comparisons. A P value of <.05 was used as the threshold for statistical significance.ResultsAt 2 weeks after treatment, the Cryo and CPMV groups, alone or combined, outperformed the control group in the treated tumor; however, the Cryo + CPMV group showed the strongest reduction and lowest variance (1.6-fold ± 0.9 vs 6.3-fold ± 0.5, P < .0001). For the untreated tumor, only Cryo + CPMV significantly reduced tumor growth compared with control (9.2-fold ± 0.9 vs 17.8-fold ± 2.1, P = .01). The Cryo + CPMV group exhibited a transient increase in interleukin-10 and persistently decreased CXCL1. Flow cytometry revealed natural killer cell enrichment in the untreated tumor and increased PD-1 expression in the spleen. Tumor-infiltrating lymphocytes increased in Cryo + CPMV–treated tumors by IHC.ConclusionsCryoablation and intratumoral CPMV, alone or combined, demonstrated potent efficacy against treated HCC tumors; however, only cryoablation combined with CPMV slowed the growth of untreated tumors, consistent with an abscopal effect.     

Stimulating Antitumoral Immunity by Percutaneous Cryoablation and Combination Immunoadjuvant Therapy in a Murine Model of Hepatocellular Carcinoma

PurposeTo test the hypothesis that antitumoral immunity can be induced after cryoablation (cryo) of hepatocellular carcinoma (HCC) through coadministration of the immunostimulant CpG and an immune checkpoint (programmed cell death 1 [PD-1]) inhibitor.Materials and MethodsSixty-three immunocompetent C57BL/6J mice were generated with 2 orthotopic HCC tumor foci: 1 for treatment and 1 to observe for antitumoral immunity. Tumors were treated with incomplete cryo alone or intratumoral CpG and/or a PD-1 inhibitor. The primary endpoint was death or when the following criteria for sacrifice were met: tumor > 1 cm (determined using ultrasound) or moribund state. Antitumoral immunity was assessed using flow cytometry and histology (tumor and liver) as well as enzyme-linked immunosorbent assay (serum). Analysis of variance was used for statistical comparisons.ResultsAt 1 week, the nonablated satellite tumor growth was reduced by 1.9-fold (P = .047) in the cryo + CpG group and by 2.8-fold (P = .007) in the cryo + CpG + PD-1 group compared with that in the cryo group. Compared with cryo alone, the time to tumor progression to endpoints was also prolonged for cryo + CpG + PD-1 and cryo + CpG mice, with log-rank hazard ratios of 0.42 (P = .031) and 0.27 (P < .001), respectively. Flow cytometry and histology showed increased cytotoxic T-cell infiltration (P = .002) and serum levels of the proinflammatory cytokine interferon-γ (P = .015) in tumors and serum of cryo + CpG mice compared with those in tumors and serum of mice treated with cryo alone. High serum levels of the anti-inflammatory cytokine tumor growth factor-β and the proangiogenesis chemokine C-X-C motif chemokine ligand 1 were correlated with a shorter time to endpoints and faster tumor growth.ConclusionsCryo combined with the immunostimulant CpG promoted cytotoxic T-cell infiltration into tumors, slowed tumor growth, and prolonged the time to progression to endpoints in an aggressive murine HCC model.     

Diagnostic Performance of CT-Guided Bone Biopsies in Patients with Suspected Osteomyelitis of the Appendicular and Axial Skeleton with a Focus on Clinical and Technical Factors Associated with Positive Microbiology Culture Results

PurposeTo assess diagnostic performance of CT-guided percutaneous needle bone biopsy (CTNBB) in patients with suspected osteomyelitis and analyze whether certain clinical or technical factors were associated with positive microbiology results.Materials and MethodsAll CTNBBs performed in a single center for suspected osteomyelitis of the appendicular and axial skeleton during 2003–2018 were retrospectively reviewed. Specific inclusion criteria were clinical and radiologic suspicion of osteomyelitis. Standard of reference was defined using outcome of surgical histopathology and microbiology culture and clinical and imaging follow-up. Technical and clinical data (needle size, comorbidities, clinical factors, laboratory values, blood cultures) were collected. Logistic regression was performed to assess associations between technical and clinical data and microbiology biopsy outcome.ResultsA total of 142 CTNBBs were included (46.5% female patients; age ± SD 46.10 y ± 22.8), 72 (50.7%) from the appendicular skeleton and 70 (49.3%) from the axial skeleton. CTNBB showed a sensitivity of 42.5% (95% confidence interval [CI], 32.0%–53.6%) in isolating the causative pathogen. A higher rate of positive microbiology results was found in patients with intravenous drug use (odds ratio [OR] = 5.15; 95% CI, 1.2–21.0; P = .022) and elevated white blood cell count ≥ 10 × 10⁹/L (OR = 3.9; 95% CI, 1.62–9.53; P = .002). Fever (≥ 38°C) was another clinical factor associated with positive microbiology results (OR = 3.6; 95% CI, 1.3–9.6; P = .011).ConclusionsCTNBB had a low sensitivity of 42.5% for isolating the causative pathogen. Rate of positive microbiology samples was significantly higher in patients with IV drug use, elevated white blood cell count, and fever.     

Ablation Therapy for Advanced Stage Non-Small Cell Lung Cancer: A National Cancer Database Study

PurposeTo compare overall survival (OS) of ablation with no treatment for patients with advanced stage non-small cell lung cancer.MethodsPatients with clinical stage IIIB (T_1–4N₃M₀, T₄N₂M₀) and stage IV (T_1–4N_0–3M₁) non-small cell lung cancer, in accordance with the American Joint Committee on Cancer, 7th edition, who did not receive treatment or who received ablation as their sole primary treatment besides chemotherapy from 2004 to 2014, were identified from the National Cancer Data Base. OS was estimated using the Kaplan-Meier method and evaluated by log-rank test, univariate and multivariate Cox proportional hazard regression, and propensity score-matched analysis. Relative survival analyses comparing age- and sex-matched United States populations were performed.ResultsA total of 140,819 patients were included. The 1-, 2-, 3- and 5-year survival rates relative to age- and sex-matched United States population were 28%, 18%, 12%, and 10%, respectively, for ablation (n = 249); and 30%, 15%, 9%, and 5%, respectively for no treatment (n = 140,570). Propensity score matching resulted in 249 patients in the ablation group versus 498 patients in the no-treatment group. After matching, ablation was associated with longer OS than that in the no-treatment group (median, 5.9 vs 4.7 months, respectively; hazard ratio, 0.844; 95% confidence interval, 0.719–0.990; P = .037). These results persisted in patients with an initial tumor size of ≤3 cm.ConclusionsPreliminary results suggest ablation may be associated with longer OS in patients with late-stage non-small cell lung cancer than survival in those who received no treatment.     

Predictors of Clinical Outcomes of Pharmacomechanical Catheter-Directed Thrombolysis for Acute Iliofemoral Deep Vein Thrombosis: Analysis of a Multicenter Randomized Trial

PurposeTo identify the baseline patient characteristics that predict who will benefit from pharmacomechanical catheter-directed thrombolysis (PCDT) of acute iliofemoral deep vein thrombosis (DVT).Materials and MethodsIn the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) multicenter randomized trial, 381 patients with acute iliofemoral DVT underwent PCDT and anticoagulation or anticoagulation alone. The correlations between baseline factors and venous clinical outcomes were evaluated over 24 months using post hoc regression analyses. Interaction terms were examined to evaluate for differential effects by treatment arm.ResultsPatients with clinically severe DVT (higher baseline Villalta score) experienced greater effects of PCDT in improving 24-month venous outcomes, including moderate or severe postthrombotic syndrome (PTS) (odds ratios [ORs] and 95% confidence intervals [CIs] per unit increase in the baseline Villalta scores were as follows: for PCDT, OR, 1.08 [95% CI, 1.01–1.15]; for control, OR, 1.20 [95% CI, 1.12–1.29]; P_interaction = .03), PTS severity (between-arm differences in the Villalta [P_interaction = .004] and Venous Clinical Severity Scale [VCSS] [P_interaction = .002)] scores), and quality of life (between-arm difference in the Venous Insufficiency Epidemiological and Economic Study Quality of Life score; P_interaction = .025). Patients with previous DVT had greater effects of PCDT on 24-month PTS severity than those in patients without previous DVT (mean [95% CI] between-arm difference in the Villalta score, 4.2 [1.56–6.84] vs 0.9 [?0.44 to 2.26], P_interaction = .03; mean [95% CI] between-arm difference in the VCSS score, 2.6 [0.94–4.21] vs 0.3 [?0.58 to 1.14], P_interaction = .02). The effects of PCDT on some but not all outcomes were greater in patients presenting with left-sided DVT (Villalta PTS severity, P_interaction = .04; venous ulcer, P_interaction = .0499) or a noncompressible popliteal vein (PTS, P_interaction = .02). The effects of PCDT did not vary by sex, race, ethnicity, body mass index, symptom duration, hypertension, diabetes, or hypercholesterolemia.ConclusionsIn patients with acute iliofemoral DVT, greater presenting clinical severity (higher baseline Villalta score) and a history of previous DVT predict enhanced benefits from PCDT.     

MR Imaging–Based In Vivo Macrophage Imaging to Monitor Immune Response after Radiofrequency Ablation of the Liver

PurposeTo establish molecular magnetic resonance (MR) imaging instruments for in vivo characterization of the immune response to hepatic radiofrequency (RF) ablation using cell-specific immunoprobes.Materials and MethodsSeventy-two C57BL/6 wild-type mice underwent standardized hepatic RF ablation (70 °C for 5 minutes) to generate a coagulation area measuring 6–7 mm in diameter. CD68⁺ macrophage periablational infiltration was characterized with immunohistochemistry 24 hours, 72 hours, 7 days, and 14 days after ablation (n = 24). Twenty-one mice were subjected to a dose-escalation study with either 10, 15, 30, or 60 mg/kg of rhodamine-labeled superparamagnetic iron oxide nanoparticles (SPIONs) or 2.4, 1.2, or 0.6 mg/kg of gadolinium-160 (¹⁶⁰Gd)-labeled CD68 antibody for assessment of the optimal in vivo dose of contrast agent. MR imaging experiments included 9 mice, each receiving 10-mg/kg SPIONs to visualize phagocytes using T2¹-weighted imaging in a horizontal-bore 9.4-T MR imaging scanner, ¹⁶⁰Gd-CD68 for T1-weighted MR imaging of macrophages, or 0.1-mmol/kg intravenous gadoterate (control group). Radiological-pathological correlation included Prussian blue staining, rhodamine immunofluorescence, imaging mass cytometry, and immunohistochemistry.ResultsRF ablation–induced periablational infiltration (206.92 μm ± 12.2) of CD68⁺ macrophages peaked at 7 days after ablation (P < .01) compared with the untreated lobe. T2¹-weighted MR imaging with SPION contrast demonstrated curvilinear T2¹ signal in the transitional zone (TZ) (186 μm ± 16.9), corresponsing to Iron Prussian blue staining. T1-weighted MR imaging with ¹⁶⁰Gd-CD68 antibody showed curvilinear signal in the TZ (164 μm ± 3.6) corresponding to imaging mass cytometry.ConclusionsBoth SPION-enhanced T2¹-weighted and ¹⁶⁰Gd-enhanced T1-weighted MR imaging allow for in vivo monitoring of macrophages after RF ablation, demonstrating the feasibility of this model to investigate local immune responses.     

Idarubicin-Loaded ONCOZENE Drug-Eluting Bead Chemoembolization in a Rabbit Liver Tumor Model: Investigating Safety,Therapeutic Efficacy,and Effects on Tumor Microenvironment

PurposeTo investigate toxicity, efficacy, and microenvironmental effects of idarubicin-loaded 40-μm and 100-μm drug-eluting embolic (DEE) transarterial chemoembolization in a rabbit liver tumor model.Materials and MethodsTwelve male New Zealand White rabbits with orthotopically implanted VX2 liver tumors were assigned to DEE chemoembolization with 40-μm (n = 5) or 100-μm (n = 4) ONCOZENE microspheres or no treatment (control; n = 3). At 24–72 hours postprocedurally, multiparametric magnetic resonance (MR) imaging including dynamic contrast-enhanced (DCE), diffusion-weighted imaging (DWI), and biosensor imaging of redundant deviation in shifts (BIRDS) was performed to assess extracellular pH (pHe), followed by immediate euthanasia. Laboratory parameters and histopathologic ex vivo analysis included fluorescence confocal microscopy and immunohistochemistry.ResultsDCE MR imaging demonstrated a similar degree of devascularization of embolized tumors for both microsphere sizes (mean arterial enhancement, 8% ± 12 vs 36% ± 51 in controls; P = .07). Similarly, DWI showed postprocedural increases in diffusion across the entire lesion (apparent diffusion coefficient, 1.89 × 10⁻³ mm²/s ± 0.18 vs 2.34 × 10⁻³ mm²/s ± 0.18 in liver; P = .002). BIRDS demonstrated profound tumor acidosis at baseline (mean pHe, 6.79 ± 0.08 in tumor vs 7.13 ± 0.08 in liver; P = .02) and after chemoembolization (6.8 ± 0.06 in tumor vs 7.1 ± 0.04 in liver; P = .007). Laboratory and ex vivo analyses showed central tumor core penetration and greater increase in liver enzymes for 40-μm vs 100-μm microspheres. Inhibition of cell proliferation, intratumoral hypoxia, and limited idarubicin elution were equally observed with both sphere sizes.ConclusionsNoninvasive multiparametric MR imaging visualized chemoembolic effects in tumor and tumor microenvironment following DEE chemoembolization. Devascularization, increased hypoxia, coagulative necrosis, tumor acidosis, and limited idarubicin elution suggest ischemia as the predominant therapeutic mechanism. Substantial size-dependent differences indicate greater toxicity with the smaller microsphere diameter.     

First-in-Human Study with Eight Patients Using an Absorbable Vena Cava Filter for the Prevention of Pulmonary Embolism

PurposeTo prospectively evaluate the initial human experience with an absorbable vena cava filter designed for transient protection from pulmonary embolism (PE).Materials and MethodsThis was a prospective, single-arm, first-in-human study of 8 patients with elevated risk of venous thromboembolism (VTE). Seven absorbable IVC filters (made of polydioxanone that breaks down into H₂O and CO₂ in 6 mo) were placed prophylactically before orthopedic (n = 5) and gynecologic (n = 2) surgeries, and 1 was placed in a case of deep vein thrombosis. Subjects underwent CT cavography and abdominal radiography before and 5, 11, and 36 weeks after filter placement to assess filter migration, embolization, perforation, and caval thrombosis and/or stenosis. Potential PE was assessed immediately before and 5 weeks after filter placement by pulmonary CT angiography.ResultsNo symptomatic PE was reported throughout the study or detected at the planned 5-week follow-up. No filter migration was detected based on the fixed location of the radiopaque markers (attached to the stent section of the filter) relative to the vertebral bodies. No filter embolization or caval perforation was detected, and no caval stenosis was observed. Throughout the study, no filter-related adverse events were reported.ConclusionsImplantation of an absorbable vena cava filter in a limited number of human subjects resulted in 100% clinical success. One planned deployment was aborted as a result of stenotic pelvic veins, resulting in 89% technical success. No PE or filter-related adverse events were observed.     

Association between Baseline Osteoarthritic Features on MR Imaging and Clinical Outcome after Genicular Artery Embolization for Knee Osteoarthritis

PurposeTo explore the association between baseline osteoarthritis (OA)-related magnetic resonance (MR) imaging features and pain reduction after genicular artery embolization (GAE) in patients with mild-to-moderate symptomatic knee OA resistant to conservative therapy.Materials and MethodsThis was a retrospective analysis of patients with mild-to-moderate symptomatic knee OA treated with GAE using imipenem-cilastatin sodium. The clinical outcome was scored at baseline and 6 months after treatment using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). MR images were scored using the MR imaging osteoarthritis knee score. Linear regression was used to evaluate associations of before-treatment MR imaging scores with WOMAC_pain and WOMAC_total reduction after 6 months.ResultsFifty-four patients (22.2% male; median age, 69.4 years; median WOMAC_pain at baseline, 12) were evaluated. Of all OA features scored, a higher cartilage full-thickness defect score showed the strongest association with less reduction of both WOMAC_pain (B,?0.63 [95% confidence interval (CI), ?0.91 to ?0.34]; P < .001) and WOMAC_total scores (B, ?1.77 [95% CI, ?2.87 to ?0.67]; P < .001) following treatment. The presence of grade 2–3 effusion synovitis (B, ?2.99 [95% CI, ?5.39 to ?0.60]) bone marrow lesions (B, ?0.52 [95% CI, ?0.86 to ?0.19]), osteophytes (B, ?0.21 [95% CI, ?0.36 to ?0.06]), and cartilage defect surface area score (B, ?0.25 [95% CI ?0.42 to ?0.08]) all showed a significant association with less WOMAC_pain reduction (all P < .05).ConclusionsIn patients with mild-to-moderate symptomatic knee OA treated with GAE, the presence and severity of full-thickness cartilage defects, effusion synovitis, bone marrow lesions, osteophytes, and cartilage surface area scores at baseline are associated with less favorable clinical outcomes at 6 months.     

Dynamic Contrast-Enhanced MR Imaging Evaluation of Perfusional Changes and Ablation Zone Size after Combination Embolization and Ablation Therapy

PurposeThe objectives of this study were to assess the utility of dynamic contrast-enhanced magnetic resonance (MR) imaging in quantifying parenchymal perfusional changes after embolization and to characterize the association between pharmacokinetic (PK) parameters and final microwave ablation volume.Materials and MethodsPK parameters from dynamic contrast-enhanced MR imaging were used to quantify perfusional changes in the liver after transarterial embolization of the right or left lobe in a swine liver model (n = 5). Each animal subject subsequently underwent microwave ablation (60 W for 5 minutes) of the embolized and nonembolized liver lobes. Changes in PK parameters from dynamic contrast-enhanced MR imaging were correlated with their respective final microwave ablation volumes in each liver lobe.ResultsMicrowave ablation volumes of embolized liver lobes were significantly larger than those of nonembolized liver lobes (28.0 mL ± 6.2 vs 15.1 mL ± 5.2, P < .001). PK perfusion parameters were significantly lower in embolized liver lobes than in nonembolized liver lobes (K^trans = 0.69 min^?1 ± 0.15 vs 1.52 min^?1 ± 0.37, P < .001; k_ep = 0.69 min^?1 ± 0.19 vs 1.54 min^?1 ± 0.42, P < .001). There was a moderate but significant correlation between normalized k_ep and ablation volume, with each unit increase in normalized k_ep corresponding to a 9.8-mL decrease in ablation volume (P = .035).ConclusionsPK-derived parameters from dynamic contrast-enhanced MR imaging can be used to quantify perfusional changes after transarterial embolization and are directly inversely correlated with final ablation volume.     

The Environmental Impact of Interventional Radiology: An Evaluation of Greenhouse Gas Emissions from an Academic Interventional Radiology Practice

PurposeTo calculate the volume of greenhouse gases (GHGs) generated by a hospital-based interventional radiology (IR) department.Materials and MethodsLife cycle assessment (LCA) was used to calculate GHGs emitted by an IR department at a tertiary care academic medical center. The volume of waste generated, amount of disposable supplies and linens used, and the operating times of electrical equipment were recorded for procedures performed between 7:00 AM and 7:00 PM on 5 consecutive weekdays. LCA was then performed using purchasing data, plug loads for electrical hardware, data from temperature control units, and estimates of emissions related to travel in the area surrounding the medical center.ResultsNinety-eight procedures were performed on 97 patients. The most commonly performed procedures were drainages (30), placement and removal of venous access (21), and computed tomography–guided biopsies (13). Approximately 23,500 kg CO₂e were emitted during the study. Sources of CO₂ emissions in descending order were related to indoor climate control (11,600 kg CO₂e), production and transportation of disposable surgical items (9,640 kg CO₂e), electricity plug load for equipment and lighting (1,060 kg CO₂e), staff transportation (524 kg CO₂e), waste disposal (426 kg CO₂e), production, laundering, and disposal of linens (279 kg CO₂e), and gas anesthetics (19.3 kg CO₂e).ConclusionsThe practice of IR generates substantial GHG volumes, a majority of which come from energy used to maintain climate control, followed by emissions related to single-use surgical supplies. Efforts to reduce the environmental impact of IR may be focused accordingly.     

The Value of Preprocedural MR Imaging in Genicular Artery Embolization for Patients with Osteoarthritic Knee Pain

PurposeTo determine the value of preprocedural MR imaging in genicular artery embolization (GAE) for patients with osteoarthritic knee pain.Materials and MethodsThis single-center study retrospectively analyzed 28 knees in 18 patients who underwent GAE for intractable knee pain < 1 month after MR imaging. The pain experienced in each knee was evaluated on a 100-mm visual analog scale (VAS) at baseline and 1- and 3-month after GAE. “GAE responders” were defined as knees that exhibited greater than 30% reduction of VAS pain scores from baseline at both follow-up visits. Musculoskeletal radiologists evaluated MR images of the affected knee compartment regarding cartilage defects, osteophytes, subchondral cysts, bone marrow lesions (BMLs), meniscal injury, and joint effusion. The performances of Kellgren–Lawrence (KL) grading and MR findings in predicting GAE responders was estimated based on receiver operating characteristic curves.ResultsThe mean VAS pain score was 84.3 mm. BML (area under the curve [AUC], 0.860; P < .001), meniscal injury (AUC, 0.811; P = .003), and KL grading (AUC, 0.898; P < .001) were significantly associated with GAE outcome. To predict GAE responders, KL grade ≤ 2 yielded a sensitivity of 87.5% and a specificity of 60.9%, BML grade ≤ 1 yielded a sensitivity of 75.0% and a specificity of 69.6%, and meniscal injury grade ≤ 2 yielded a sensitivity of 83.3% and a specificity of 72.7%.ConclusionsLarge BMLs and severe meniscal injuries on MR imaging, as well as high KL grades, indicated poor responses to GAE.     

Robotically-Assisted Sonic Therapy for Renal Ablation in a Live Porcine Model: Initial Preclinical Results

PurposeTo demonstrate the feasibility of Robotically Assisted Sonic Therapy (RAST)—a noninvasive and nonthermal focused ultrasound therapy based on histotripsy—for renal ablation in a live porcine model.Materials and MethodsRAST ablations (n = 11) were performed in 7 female swine: 3 evaluated at 1 week (acute) and 4 evaluated at 4 weeks (chronic). Treatment groups were acute bilateral (3 swine, 6 ablations with immediate computed tomography [CT] and sacrifice); chronic single kidney (3 swine, 3 ablations; CT at day 0, week 1, and week 4 after treatment, followed by sacrifice); and chronic bilateral (1 swine, 2 ablations). Treatments were performed using a prototype system (VortxRx; HistoSonics, Inc) and targeted a 2.5-cm-diameter sphere in the lower pole of each kidney, intentionally including the central collecting system.ResultsMean treatment time was 26.4 minutes. Ablations had a mean diameter of 2.4 ± 0.3 cm, volume of 8.5 ± 2.4 cm³_, and sphericity index of 1.00. Median ablation volume decreased by 96.1% over 4 weeks. Histology demonstrated complete lysis with residual blood products inside the ablation zone. Temporary collecting system obstruction by thrombus was observed in 4/11 kidneys (2 acute and 2 chronic) and resolved by 1 week. There were no urinary leaks, main vessel thromboses, or adjacent organ injuries on imaging or necropsy.ConclusionsIn this normal porcine model, renal RAST demonstrated complete histologic destruction of the target renal tissue while sparing the urothelium.     

Potential of employing a quantum iterative reconstruction algorithm for ultra-high-resolution photon-counting detector CT of the hip

IntroductionThis study investigated the image quality of a new quantum iterative reconstruction algorithm (QIR) for high resolution photon-counting CT of the hip.MethodsUsing a first-generation photon-counting CT scanner, five cadaveric specimens were examined with ultra-high-resolution protocols matched for radiation dose. Images were post-processed with a sharp convolution kernel and five different strength levels of iterative reconstruction (QIR 0 – QIR 4). Subjective image quality was rated independently by three radiologists on a five-point scale. Intraclass correlation coefficients (ICC) were computed for assessing interrater agreement. Objective image quality was evaluated by means of contrast-to-noise-ratios (CNR) in bone and muscle tissue.ResultsFor osseous tissue, subjective image quality was rated best for QIR 2 reformatting (median 5 [interquartile range 5–5]). Contrarily, for soft tissue, QIR 4 received the highest ratings among compared strength levels (3 [3–4]). Both ICC_bone (0.805; 95% confidence interval 0.711–0.877; p < 0.001) and ICC_muscle (0.885; 0.824–0.929; p < 0.001) suggested good interrater agreement. CNR in bone and muscle tissue increased with ascending strength levels of iterative reconstruction with the highest results recorded for QIR 4 (CNR_bone 29.43 ± 2.61; CNR_muscle 8.09 ± 0.77) and lowest results without QIR (CNR_bone 3.90 ± 0.29; CNR_muscle 1.07 ± 0.07) (all p < 0.001).ConclusionReconstructing photon-counting CT data with an intermediate QIR strength level appears optimal for assessment of osseous tissue, whereas soft tissue analysis benefitted from applying the highest strength level available.Implications for practiceQuantum iterative reconstruction technique can enhance image quality by significantly reducing noise and improving CNR in ultra-high resolution CT imaging of the hip.     

Clinical Safety and Efficacy of Locoregional Therapy Combined with Adoptive Transfer of Allogeneic γδ T Cells for Advanced Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

PurposeTo investigate the safety and efficacy of locoregional therapy plus adoptive transfer of allogeneic gamma delta (γδ) T cells for patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).MethodsThirty patients with HCC and 29 patients with ICC were randomly assigned to receive locoregional therapy (HCC, Group A, n = 15; ICC, Group C, n = 15) or locoregional therapy plus γδ T cell therapy (HCC, Group B, n = 15; ICC, Group D, n = 14). Groups A and C only received locoregional ablation (cryoablation or irreversible electroporation), whereas Groups B and D received locoregional therapy followed by adoptive transfer of allogeneic γδ T cells. The primary endpoints were safety, distant progression-free survival (PFS), local PFS, and overall survival (OS).ResultsThe median distant PFS was significantly longer in the combined treatment groups than the locoregional treatment groups (HCC: 8 vs 4 months, P = .04; ICC: 8 vs 4 months, P = .021). There was no significant difference in local PFS between the 2 treatment modalities. Patients with HCC in the combined treatment group had a longer OS (median OS: 13 vs 8 months, P = .029). However, there was no significant difference in OS in patients with ICC between the 2 treatment modalities (median OS: 9.5 vs 8 months, P = .546). All adverse events were manageable with no significant difference in incidence between groups.ConclusionsThe novel combination of locoregional ablation with adoptive transfer of allogeneic γδ cells was safe, with encouraging clinical efficacy against HCC and ICC.     

Pharmacokinetics and Early Tumor Response to Conventional Transarterial Chemoembolization with Sorafenib and Doxorubicin in a VX2 Rabbit Tumor Model

PurposeTo investigate the pharmacokinetics (PK) and early effects of conventional transarterial chemoembolization (TACE) using sorafenib and doxorubicin on tumor necrosis, hypoxia markers, and angiogenesis in a rabbit VX2 liver tumor model.Materials and MethodsVX2 tumor-laden New Zealand White rabbits (N = 16) were divided into 2 groups: 1 group was treated with hepatic arterial administration of ethiodized oil and doxorubicin emulsion (DOX-TACE), and the other group was treated with ethiodized oil, sorafenib, and doxorubicin emulsion (SORA-DOX-TACE). Animals were killed within 3 days of the procedure. Levels of sorafenib and doxorubicin were measured in blood, tumor, and adjacent liver using mass spectrometry. Tumor necrosis was determined by histopathological examination. Intratumoral hypoxia-inducible factor (HIF) 1α, vascular endothelial growth factor (VEGF), and microvessel density (MVD) were determined by immunohistochemistry.ResultsThe median intratumoral concentration of sorafenib in the SORA-DOX-TACE group was 17.7 μg/mL (interquartile range [IQR], 7.42–33.5 μg/mL), and its maximal plasma concentration (C_max) was 0.164 μg/mL (IQR, 0.0798–0.528 μg/mL). The intratumoral concentration and C_max of doxorubicin were similar between the groups: 4.08 μg/mL (IQR, 3.18–4.79 μg/mL) and 0.677 μg/mL (IQR, 0.315–1.23 μg/mL), respectively, in the DOX-TACE group and 1.68 μg/mL (IQR, 0.795–4.08 μg/mL) and 0.298 μg/mL (IQR, 0.241–0.64 μg/mL), respectively, in the SORA-DOX-TACE group. HIF-1α expression was increased in the SORA-DOX-TACE group than in the DOX-TACE group. Tumor volume, tumor necrosis, VEGF expression, and MVD were similar between the 2 groups.ConclusionsThe addition of sorafenib to DOX-TACE delivered to VX2 liver tumors resulted in high intratumoral and low systemic concentrations of sorafenib without altering the PK of doxorubicin.     

Evaluation of an Integrated Spectroscopy and Classification Platform for Point-of-Care Core Needle Biopsy Assessment: Performance Characteristics from Ex Vivo Renal Mass Biopsies

PurposeTo evaluate a transmission optical spectroscopy instrument for rapid ex vivo assessment of core needle cancer biopsies (CNBs) at the point of care.Materials and MethodsCNBs from surgically resected renal tumors and nontumor regions were scanned on their sampling trays with a custom spectroscopy instrument. After extracting principal spectral components, machine learning was used to train logistic regression, support vector machines, and random decision forest (RF) classifiers on 80% of randomized and stratified data. The algorithms were evaluated on the remaining 20% of the data set held out during training. Binary classification (tumor/nontumor) was performed based on a decision threshold. Multinomial classification was also performed to differentiate between the subtypes of renal cell carcinoma (RCC) and account for potential confounding effects from fat, blood, and necrotic tissue. Classifiers were compared based on sensitivity, specificity, and positive predictive value (PPV) relative to a histopathologic standard.ResultsA total of 545 CNBs from 102 patients were analyzed, yielding 5,583 spectra after outlier exclusion. At the individual spectra level, the best performing algorithm was RF with sensitivities of 96% and 92% and specificities of 90% and 89%, for the binary and multiclass analyses, respectively. At the full CNB level, RF algorithm also showed the highest sensitivity and specificity (93% and 91%, respectively). For RCC subtypes, the highest sensitivity and PPV were attained for clear cell (93.5%) and chromophobe (98.2%) subtypes, respectively.ConclusionsEx vivo spectroscopy imaging paired with machine learning can accurately characterize renal mass CNB at the time of tissue acquisition.