Inhibition of Growth in a Rabbit VX2 Thigh Tumor Model with Intraarterial Infusion of Carbon Dioxide–Saturated Solution

PurposeTo evaluate the efficacy of intraarterial infusion of CO₂-saturated solution in rabbit VX2 thigh tumors.Materials and MethodsFourteen Japanese white rabbits had VX2 tumors implanted in the right femoral muscle 3 weeks before intraarterial infusion. Rabbits were divided into control and CO₂ groups (n = 7 each). Fifty milliliters of solution (saline solution and CO₂-saturated solution for the control and CO₂ groups, respectively) was administered via a 24-gauge catheter in the ipsilateral iliac artery close to the feeding artery of the VX2 tumor. All rabbits were killed for tumor harvest on day 3 after the procedure. Tumor volume was evaluated with in vivo direct caliper measurement and contrast-enhanced computed tomography (CT). Tumor apoptotic changes were examined by DNA fragmentation assay and immunoblot analysis. The tumor growth ratio and apoptotic cell rate were analyzed.ResultsBody weight was equally increased in both groups, but the mean tumor growth ratio was significantly decreased in the CO₂ group compared with the control group (−9.5% ± 7.9 vs 27.2% ± 6.6 and 4.1% ± 4.4 vs 35.7% ± 4.5 measured by calipers and contrast-enhanced CT, respectively; P < .01). Apoptotic activity in the CO₂ group was higher than in the control group (number of apoptotic cells per area, 215.0 ± 58.7 vs 21.8 ± 5.4; adjusted relative density of cleaved caspase-3, 0.23 ± 0.07 vs 0.04 ± 0.01; P < .01).ConclusionsIntraarterial infusion of CO₂-saturated solution inhibits rabbit VX2 thigh tumor growth by activation of apoptotic cell death through cleaved caspase-3 upregulation.     

Stabilization Improves Theranostic Properties of Lipiodol®-Based Emulsion During Liver Trans-arterial Chemo-embolization in a VX2 Rabbit Model

CardioVascular and Interventional Radiology - To demonstrate that stability is a crucial parameter for theranostic properties of Lipiodol®-based emulsions during liver trans-arterial...     

Safety and Efficacy of Transjugular Liver Biopsy in Patients with Left Lobe–Only Liver Transplants

PurposeTo evaluate efficacy and safety of transjugular liver biopsy (TJLB) via the left hepatic vein in patients with left lobe–only liver transplants (LLOTs).Materials and MethodsRetrospective review revealed 43 TJLBs performed in 26 patients with LLOTs (mean age 51.3 y; range, 18–73 y) between January 2009 and June 2016 at a single institution. A comparison group of 44 randomly selected TJLBs performed in 37 orthotopic whole liver transplant (OWLT) recipients (mean age 57.6 y; range, 35–74 y) during the same time period was evaluated. Patient demographics, type and age of transplant, technical success, adequacy of samples, number of portal tracts obtained, pathologic diagnosis, and complication rate were reviewed.ResultsTechnical success was achieved in 98% (42/43) of LLOT procedures. TJLB failed in 1 patient with LLOT, in whom no patent hepatic veins were identified. Technical success was achieved in 100% (44/44) in the OWLT group. Mean (SD) number of needle passes was 4.12 (1.25) in the LLOT group vs 3.95 (1.28) in the OWLT group (P = .54). Mean (SD) specimen length was 1.16 (0.75) cm in the LLOT group vs 1.19 (0.58) cm in the OWLT group (P = .78). Mean (SD) number of portal tracts obtained in the LLOT group was 10.7 (5.26) vs 12.3 (4.68) in the OWLT group (P = .17). No major complications were observed in either group.ConclusionsTJLB in adult patients with LLOTs appears safe and feasible, with favorable rates of technical success and adequacy of sampling.     

Chemoembolization of Hepatocellular Carcinoma with Hepasphere 30–60 μm. Safety and Efficacy Study

Background

This study examined the safety, pharmacokinetics, and efficacy of transarterial chemoembolization of hepatocellular carcinoma (HCC) using a newly developed size of a superabsorbent polymer drug-eluting embolic material.

Methods

Forty-five patients with documented HCC (Child–Pugh score A/B: 55.5 %/44.5 %) were embolized with HepaSphere microspheres 30–60 μm with escalation of lesion, dose, and frequency of re-embolization. Local response was evaluated with modified response evaluation criteria in solid tumors (mRECIST). Plasma levels of doxorubicin were measured in 24 patients at baseline and at 5, 20, 40, 60, and 120 min, at 6, 24, and 48 h, and at 7 days, respectively, to determine doxorubicin in plasma (Cmax) and area under the curve (AUC). Measurements of three patients who underwent lipiodol-based conventional chemoembolization (c-TACE) were also performed.

Results

TACE with HepaSphere was well tolerated with an acceptable safety profile and no 30-day mortality. Response rates were calculated on intention-to-treat basis with complete response (CR) in 17.8 % reaching 22.2 % for the target lesion. Overall partial response (PR) was seen in 51.1 %, stable disease in 20 %, and progressive disease in 11.1 % of patients. Overall objective response (CR + PR), including patients treated at all dosages of doxorubicin, was seen in 68.9 % of cases. After a median follow-up of 15.6 months, 1-year survival is 100 %. Doxorubicin AUC was significantly lower in patients with HepaSphere 30–60 μm (35,195 ± 27,873 ng × min/ml) than in patients with conventional TACE (103,960 ± 16,652 ng × min/ml; p = 0.009). Cmax was also significantly lower with HepaSphere 30–60 μm (83.9 ± 32.1 ng/ml) compared with c-TACE (761.3 ± 58.8 ng/ml; p = 0.002).

Conclusion

HepaSphere 30–60 μm is an effective drug-eluting embolic material with a favourable pharmacokinetic profile.     

Percutaneous Intraportal Application of Adipose Tissue–derived Mesenchymal Stem Cells Using a Balloon Occlusion Catheter in a Porcine Model of Liver Fibrosis

PurposeTo investigate the safety and effectiveness of a novel endovascular approach for therapeutic cell delivery using a balloon occlusion catheter in a large animal model of liver fibrosis.Materials and MethodsTranscatheter arterial embolization with ethiodized oil (Ethiodol) and ethanol was used to induce liver damage in 11 pigs. Mesenchymal stem cells (MSCs) were harvested from adipose tissue and engineered to express green fluorescent protein (GFP). A balloon occlusion catheter was positioned in the bilateral first-order portal vein branches 2 weeks after embolization to allow intraportal application of MSCs in six experimental animals. MSCs were allowed to dwell for 10 minutes using prolonged balloon inflation. Five control animals received a sham injection of normal saline in a similar fashion. Hepatic venous pressure gradient (HVPG) was measured immediately before necropsy. Specimens from all accessible lobes were obtained with ultrasound-guided percutaneous 18-gauge biopsy 2 hours after cell application. All animals were euthanized within 4 weeks. Fluorescent microscopy was used to assess the presence and distribution of cells.ResultsLiver injury and fibrosis were successfully induced in all animals. MSCs (6–10 × 10⁷) were successfully delivered into the portal vein in the six experimental animals. Cell application was not associated with vascular complications. HVPG showed no instances of portal hypertension. GFP-expressing MSCs were visualized in biopsy specimens and were distributed primarily within the sinusoidal spaces; however, 4 weeks after implantation, MSCs could not be identified in histologic specimens.ConclusionsA percutaneous endovascular approach for cell delivery using a balloon occlusion catheter proved safe for intraportal MSC application in a large animal model of liver fibrosis.     

Evaluation of the In Vivo Efficiency and Safety of Hepatic Radiofrequency Ablation Using a 15-G Octopus? in Pig Liver

Objective

To determine in vivo efficacy of radiofrequency ablation (RFA) in porcine liver by using 15-gauge Octopus® (15-G Octopus®) electrodes to create a large coagulation.

Materials and Methods

A total of 18 coagulations were created by using a 180-W generator and 15-G Octopus® electrodes during laparotomy, performed in 14 pigs. Coagulation necrosis was created in the pig livers by the use of one of three RFA protocols: 1) group A, monopolar RFA using a 15-G Octopus® electrode with a 5-mm inter-electrode distance (n = 4); 2) group B, monopolar RFA using a 15-G Octopus® electrode with a 10-mm inter-electrode distance (n = 6); and 3) group C, switching monopolar RFA using two 15-G Octopus® electrodes (n = 8). The energy efficiency, shape, maximum and minimum diameters (Dmx and Dmi), and the volume of the coagulation volume were measured in each group. The Summary statistics were obtained and Mann-Whitney test was were performed.

Results

The mean ablated volume of each group was 49.23 cm³ in A, 64.11 cm³ in B, and 72.35 cm³ in C. The mean Dmx and Dmi values were 5.68 cm and 4.58 cm in A and 5.97 cm and 4.97 cm in B, respectively. In group C, the mean diameters of Dmx and Dmi were 6.80 cm and 5.11 cm, respectively. The mean ratios of Dmi/Dmx were 1.25, 1.20, and 1.35 in groups A, B, and C, respectively. There was one animal death during the RFA procedure, the cause of which could not be subsequently determined. However, there were no other significant, procedure-related complications during the seven-hour-delayed CT scans.

Conclusion

RFA procedures using 15-G Octopus® electrodes are useful and safe for creating a large ablation in a single electrode model as well as in the multiple electrodes model.     

Hepatic Intra-arterial Delivery of a “Trojan-horses” Gene Therapy: A Pilot Study on Rabbit VX2 Hepatic Tumor Model

CardioVascular and Interventional Radiology - Gene-directed enzyme prodrug therapy (GDEPT) is a “Trojan-horses” suicide gene therapy that consists of tumor-targeted gene delivery...     

Dual-Energy CT–Derived Volumetric Iodine Concentration for the Assessment of Therapeutic Response after Microwave Ablation in a Rabbit Model with Intrahepatic VX2 Tumor

Purpose

To evaluate whether changes in volumetric iodine concentration (VIC) could serve as a suitable predictor of therapeutic response to microwave (MW) ablation in a rabbit intrahepatic VX2 tumor model.

Does Artificial Ascites Induce the Heat-Sink Phenomenon during Percutaneous Radiofrequency Ablation of the Hepatic Subcapsular Area?: an in vivo Experimental Study Using a Rabbit Model

Objective

To evaluate the effect of the heat-sink phenomenon induced by artificial ascites on the size of the ablation zone during percutaneous radiofrequency (RF) ablation of the hepatic subcapsular area in an in vivo rabbit model.

Materials and Methods

A total of 21 percutaneous rabbit liver RF ablations were performed with and without artificial ascites (5% dextrose aqueous solution). The rabbits were divided into three groups: a) control group (C, n = 7); b) room temperature ascites group (R, n = 7); and c) warmed ascites group (W, n = 7). The tip of a 1 cm, internally cooled electrode was placed on the subcapsular region of the hepatic dome via ultrasound guidance, and ablation was continued for 6 min. Changes in temperature of the ascites were monitored during the ablation. The size of the ablation zones of the excised livers and immediate complications rates were compared statistically between the groups (Mann-Whitney U test, Kruskal-Wallis test, linear-by-linear association, p = 0.05).

Results

One rabbit from the "W" group expired during the procedure. In all groups, the ascites temperatures approached their respective body temperatures as the ablations continued; however, a significant difference in ascites temperature was found between groups "W" and "R" throughout the procedures (39.2±0.4℃ in group W and 33.4±4.3℃ in group R at 6 min, p = 0.003). No significant difference was found between the size of the ablation zones (782.4±237.3 mL in group C, 1,172.0±468.9 mL in group R, and 1,030.6±665.1 mL in group W, p = 0.170) for the excised liver specimens. Diaphragmatic injury was identified in three of seven cases (42.9%) upon visual inspection of group "C" rabbits (p = 0.030).

Conclusion

Artificial ascites are not likely to cause a significant heat-sink phenomenon in the percutaneous RF ablation of the hepatic subcapsular region.     

Multimodal Visibility of a Modified Polyzene-F–coated Spherical Embolic Agent for Liver Embolization: Feasibility Study in a Porcine Model

PurposeTo evaluate multimodal visibility of modified currently available microspheres on radiography, magnetic resonance (MR) imaging, and computed tomography (CT) in a porcine liver model.Materials and MethodsLivers of four pigs were embolized with two sizes (100 μm ± 25 and 700 μm ± 50) of modified Embozene Microspheres embedded with different densities of barium sulfate and iodine as radiopaque materials (intensity groups A–C, with increasing intensity from A to C for 100 μm and intensities A and C for 700 μm) and iron oxide as magnetic substance for MR imaging visibility. Pigs embolized with currently available Embozene Microspheres served as control groups. Pre- and postinterventional MR imaging (T1- and T2-weighted) and CT were performed. Qualitative and quantitative (ie, determination of signal-to-noise ratio [SNR]) particle visibility was evaluated on radiography, MR imaging, and CT.ResultsModified particles of both sizes were visible on radiography, MR imaging, and CT. Particles in the control group were not visible. For modified particles of both sizes, SNRs measured on MR imaging decreased significantly after embolization (eg, cluster analysis of group A, 100 μm ± 50 particles, T1-weighted, ?74.6% ± 3.4; P = .03). For modified particles of both sizes, SNR measured on CT increased significantly after embolization (eg, cluster analysis of group A, 700 μm ± 25 particles, +54.3% ± 13.5; P = .03).ConclusionsModification of currently available Embozene Microspheres was successful, with multimodal visibility on radiography, MR imaging, and CT in porcine liver. In the future, this might improve procedure accuracy and allow monitoring, control, and improvement of embolotherapy during and after the procedure.     

Iron-Oxide Nanocluster Labeling of Clostridium novyi-NT Spores for MR Imaging–Monitored Locoregional Delivery to Liver Tumors in Rat and Rabbit Models

PurposeTo label Clostridium novyi-NT spores (C. novyi-NT) with iron oxide nanoclusters and track distribution of bacteria during magnetic resonance (MR) imaging-monitored locoregional delivery to liver tumors using intratumoral injection or intra-arterial transcatheter infusion.Materials and MethodsVegetative state C. novyi-NT were labeled with iron oxide particles followed by induction of sporulation. Labeling was confirmed with fluorescence microscopy and transmission electron microscopy (TEM). T2 and T2* relaxation times for magnetic clusters and magnetic microspheres were determined using 7T and 1.5T MR imaging scanners. In vitro assays compared labeled bacteria viability and oncolytic potential to unlabeled controls. Labeled spores were either directly injected into N1-S1 rodent liver tumors (n = 24) or selectively infused via the hepatic artery in rabbits with VX2 liver tumors (n = 3). Hematoxylin-eosin, Prussian blue, and gram staining were performed. Statistical comparison methods included paired t-test and ANOVA.ResultsBoth fluorescence microscopy and TEM studies confirmed presence of iron oxide labels within the bacterial spores. Phantom studies demonstrated that the synthesized nanoclusters produce R2 relaxivities comparable to clinical agents. Labeling had no significant impact on overall growth or oncolytic properties (P >.05). Tumor signal-to-noise ratio (SNR) decreased significantly following intratumoral injection and intra-arterial infusion of labeled spores (P <.05). Prussian blue and gram staining confirmed spore delivery.ConclusionsC. novyi-NT spores can be internally labeled with iron oxide nanoparticles to visualize distribution with MR imaging during locoregional bacteriolytic therapy involving direct injection or intra-arterial transcatheter infusion.     

Pharmacokinetics of [18F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer’s disease

Purpose

The aim of this study was to investigate the potential of [¹⁸F]flutemetamol as a preclinical PET tracer for imaging β-amyloid (Aβ) deposition by comparing its pharmacokinetics to those of [¹¹C]Pittsburgh compound B ([¹¹C]PIB) in wild-type Sprague Dawley rats and C57Bl/6N mice. In addition, binding of [¹⁸F]flutemetamol to Aβ deposits was studied in the Tg2576 transgenic mouse model of Alzheimer’s disease.

Methods

[¹⁸F]Flutemetamol biodistribution was evaluated using ex vivo PET methods and in vivo PET imaging in wild-type rats and mice. Metabolism and binding of [¹¹C]PIB and [¹⁸F]flutemetamol to plasma proteins were analysed using thin-layer chromatography and ultrafiltration methods, respectively. Radiation dose estimates were calculated from rat ex vivo biodistribution data. The binding of [¹⁸F]flutemetamol to Aβ deposits was also studied using ex vivo and in vitro autoradiography. The location of Aβ deposits in the brain was determined with thioflavine S staining and immunohistochemistry.

Results

The pharmacokinetics of [¹⁸F]flutemetamol resembled that of [¹¹C]PIB in rats and mice. In vivo studies showed that both tracers readily entered the brain, and were excreted via the hepatobiliary pathway in both rats and mice. The metabolism of [¹⁸F]flutemetamol into radioactive metabolites was faster than that of [¹¹C]PIB. [¹⁸F]Flutemetamol cleared more slowly from the brain than [¹¹C]PIB, particularly from white matter, in line with its higher lipophilicity. Effective dose estimates for [¹¹C]PIB and [¹⁸F]flutemetamol were 2.28 and 6.65?μSv/MBq, respectively. Autoradiographs showed [¹⁸F]flutemetamol binding to fibrillar Aβ deposits in the brain of Tg2576 mice.

Conclusion

Based on its pharmacokinetic profile, [¹⁸F]flutemetamol showed potential as a PET tracer for preclinical imaging. It showed good brain uptake and was bound to Aβ deposits in the brain of Tg2576 mice. However, its high lipophilicity might complicate the analysis of PET data, particularly in small-animal imaging.     

Effectiveness of Repeat Angiographic Assessment in Patients Designated for Radioembolization Using Yttrium-90 Microspheres With Initial Extrahepatic Accumulation of Technitium-99m Macroaggregated Albumin: A Single Center’s Experience

Purpose

To evaluate the efficacy of a workflow consisting of repeat assessment in patients planned for yttrium-90 (⁹⁰Y) radioembolization in case of nontarget visceral technetium-99m (^99mTc)-macroaggregated albumin (MAA) accumulation despite initial prophylactic coil embolization of nonhepatic arteries.

Materials and Methods

In 341 patients with primary and secondary liver cancer, pretreatment hepatic angiograms, as well as single-photon emission computed tomography coregistered with magnetic resonance imaging scans, were obtained. Extrahepatic tracer deposition was identified in 33 patients (9.7%) necessitating repeat assessment. Images were reviewed to correlate the site of MAA accumulation with causative gastrointestinal vessels, and repeat angiograms served as reference standard.

Results

At repeat angiography, the source of extrahepatic flow was identified and eliminated in 31 of 33 patients (93.9%). In 20 patients (60.6%), successful embolization of nontarget vessels was achieved, in 13 patients (39.4%), MAA was administered more distally. Afterward, extrahepatic MAA deposition was eliminated in 30 patients (90.9%).

Conclusion

The algorithm of repeat assessment in case of extrahepatic MAA accumulation has proven highly effective to eliminate extrahepatic shunting, thus decreasing the risk of postradioembolization complications due to inadvertent visceral microsphere deposition.     

Liver Hypertrophy After Percutaneous Portal Vein Embolization: Comparison of N-Butyl-2-Cyanocrylate Versus Sodium Acrylate�CVinyl Alcohol Copolymer Particles in a Swine Model

Purpose  

Percutaneous portal vein embolization (PPVE) induces hypertrophy of the future liver remnant before hepatic resection. The ideal embolic material has not yet been determined. We compared N-butyl-2-cyanocrylate (NBCA) with sodium acrylate–vinyl alcohol copolymer particles using a swine model.     

Portal Vein Embolization in the Setting of Staged Hepatectomy with Preservation of Segment IV ± I Only for Bilobar Colorectal Liver Metastases: Safety,Efficacy, and Clinical Outcomes

Purpose

To assess frequency of adverse events, efficacy, and clinical outcomes of percutaneous portal vein embolization (PVE) in patients with bilobar colorectal liver metastases undergoing staged hepatectomy with preservation of segment IV ± I only.

Synthesis and evaluation of Tc-99m DTPA–glutathione as a non-invasive tumor imaging agent in a mouse colon cancer model

Purpose

Glutathione (GSH) plays a critical role in detoxification reactions by reducing the levels of reactive oxygen species in cancer cells. This study aimed to develop technetium (Tc)-99m diethylenetriaminepentaacetic acid (DTPA)–GSH as a tumor imaging agent, and to evaluate the diagnostic performance of Tc-99m DTPA–GSH in terms of its ability to differentiate tumors from inflammatory lesions.

Methods

DTPA–GSH was synthesized by reaction of GSH with DTPA anhydride under anhydrous conditions in a nitrogen atmosphere. DTPA–GSH was then reacted with Tc-99m sodium pertechnetate in a tin (II) chloride (SnCl₂) solution. Gamma camera imaging was performed after intravenous injection of Tc-99m DTPA–GSH into a mouse CT-26 colon cancer model, or a mouse model of inflammation induced by the intramuscular injection of Freund’s complete adjuvant.

Results

DTPA–GSH was successfully prepared via a straightforward synthetic procedure and radiolabeled with Tc-99m at a high labeling efficiency (>95 %). Tc-99m DTPA–GSH was strongly internalized by tumors in colon cancer model mice, with the tumor-to-normal muscle ratio of the complex reaching 4.3 ± 0.9 at 4 h. By contrast, Tc-99m DTPA–GSH showed relatively weak uptake in inflammatory lesions (target-to-non-target ratio = 2.0 ± 0.3 at 4 h). A competition study showed that the uptake of Tc-99m DTPA–GSH into tumors was blocked by co-injection with high concentrations of free GSH.

Conclusions

The results of this work indicate that Tc-99m DTPA–GSH is a good candidate for development as a non-invasive tumor imaging agent. Furthermore, Tc-99m DTPA–GSH effectively distinguished between cancerous tissue and inflammatory lesions.     

US, CT, and MR imaging of hepatic masses in Alström syndrome: a case report

Alstr?m syndrome is among the rarest genetic disorders described in the medical literature. It is characterized by retinal pigment degeneration, obesity, sensorineural deafness, non-insulin-dependent diabetes mellitus, progressive chronic nephropathy, cardiomyopathy, and hepatic dysfunction. Hepatic inflammation and fibrosis, which leads to cirrhosis, portal hypertension, and liver failure, is the final pathway of the hepatopathy in Alstr?m syndrome. We report a case of Alstr?m syndrome with particular emphasis on hepatic findings.     

Efficacy and safety of direct aspiration first pass technique versus stent-retriever thrombectomy in acute basilar artery occlusion—a retrospective single center experience

Introduction

The study aimed to compare efficacy and safety of aspiration thrombectomy (AT) to stentriever thrombectomy (SRT) in patients with basilar artery (BA) occlusion (BAO).

Methods

We retrospectively included patients with the following characteristics: acute BAO or occlusion of the intracranial vertebral artery (ICVA) and endovascular therapy (EVT) with stentriever (SRT) or aspiration thrombectomy (AT). Additional extra- but not intracranial EVT and intravenous thrombolysis (IVT) were allowed.

Results

Between January 2013 and April 2016, 33 patients fulfilled the criteria (13 treated with SRT, 20 with AT). Prior to EVT, 23 (70%) patients received IVT. The proximal intracranial occlusion was ICVA in 2 patients, proximal BA in 5 patients, middle BA in 20 patients, and distal BA in 6 patients. Mean time to treatment was 334 min (95% CI 276–391 min). Procedure duration differed significantly (p = 0.002) as follows: 97 min with SRT (95% CI 69–124 min) and 55 min with AT (95% CI 43–66 min). Recanalization (arterial occlusive lesion (AOL) 2/3) was achieved in 26 patients (79%). Complete recanalization (AOL 3) happened more often with AT (75% (95% CI 65–85%)) compared to SRT (46% (95% CI 32–60%)). Conversion rate 6% (two patients). Hemorrhages occurred in 12 (36%) patients, periprocedural complications in eight (three dissections, five embolizations to new territory) (no group difference). Ten patients (30%) had a favorable outcome (mRS ≤3) at discharge; mortality rate was 24% (eight deaths) (no group difference).

Conclusion

In primarily embolic BAO, aspiration thrombectomy was faster, effective and not detrimental to outcome as compared to stentriever thrombectomy. Thus, it may be justified to use aspiration thrombectomy as first-line treatment in these patients.