A Pilot First-in-Human Study of Embrace,a Polyethylene Glycol-Based Liquid Embolic Agent,in the Embolization of Malignant and Benign Hypervascular Tumors

PurposeTo investigate the safety and efficacy of an aqueous polyethylene glycol-based liquid embolic agent, Embrace Hydrogel Embolic System (HES), in the treatment of benign and malignant hypervascular tumors.Materials and MethodsA prospective, single-arm, multicenter study included 8 patients, 5 males and 3 females, with a median age of 58.5 years (30–85 years), who underwent embolization in 8 tumors between October 2019 and May 2020. Technical success was defined as successful delivery of HES to the index vessel, with disappearance of >90% of the targeted vascular enhancement or, for portal vein embolization, occlusion of the portal branches to the liver segments for future resection. The volume of HES administered, ease of use (5 point Likert scale), administration time, and adverse events (AEs) were recorded. Evaluation was performed at 7, 30, and 90 days via clinical assessment and blood testing, and follow-up imaging was performed at 30 days.ResultsEight patients were enrolled, and 10 embolizations were performed in 8 lesions. Tumors included hepatocellular carcinoma (n = 4), renal angiomyolipoma (n = 3), and intrahepatic cholangiocarcinoma (n = 1). Technical success was 100%, and the average ease of use was 3.3 ± 1.0 SD. The HES delivery time was 1–28 minutes (median, 16.5 minutes), and the HES volume injected was 0.4–4.0 mL (median, 1.3 mL). All patients reached 30-day follow-up with imaging, and 6 patients reached 90-day follow-up. There were 3 serious AEs in 2 patients that were unrelated to the embolic agent.ConclusionHES resulted in a 100% embolization technical success rate. The product ease of use was acceptable, and no target vessel recanalization was noted on follow-up imaging at 30 days.     

Embolic Characteristics of Imipenem-Cilastatin Particles in Vitro and in Vivo: Implications for Transarterial Embolization in Joint Arthropathies

PurposeTo elucidate in vitro and in vivo characteristics and embolic properties of imipenem-cilastatin (IPM-CS) compared with hydrogel microspheres.Materials and MethodsParticle size distribution was microscopically evaluated with 3 samples of 50 mg IPM-CS suspensions in each of 6 conditions by a mixture of contrast volume: 500 or 1000 μL and vortex mixing time: 5, 10, or 30 s. Time-dependent changes up to 3 h post-mixing were also evaluated. Fifteen male Sprague-Dawley rats (460.2 ± 5.0 g) underwent unilateral renal artery embolization using IPM-CS (n = 11) or hydrogel microspheres (n = 4). Follow-up angiography 48 h after embolization and histological evaluation, including acute tubular necrosis (ATN) and inflammation, were scored using a 5-point scale (from 0 = normal to 4 = severe).ResultsOver 91% of IPM-CS particles were <40 μm under all in vitro conditions. With the increased contrast volume, the average particle size also increased (mean ± standard deviation: 11.6 ± 13.9 vs 16.7 ± 18.2 μm for 500 and 1000 μL iodinated contrast, P < .001); however, the impact of the mixing/elapsed time were limited. At 48 h after embolization, all cases in the IPM-CS groups (11/11) showed major to complete recanalization versus no recanalization with hydrogel microspheres (0/4) (P < .001). The following are the median ATN and inflammation grades in the cortex (ventral/dorsal) and medulla (ventral/dorsal) in both groups: IPM-CS, ATN in cortex (2/4) and medulla (1/1), inflammation in cortex (0/0) and medulla (0/0); hydrogel microspheres, ATN in cortex (4/4) and medulla (3/2), inflammation in cortex (1/1) and medulla (1/1).ConclusionsIPM-CS suspension generated particles that were predominantly smaller than 40 μm and with unique short-term embolic effects, leaving predominantly peripheral ischemic changes.     

Biodegradable Polydioxanone Microspheres for Transcatheter Arterial Embolization: Proof of Principle

PurposeTo evaluate feasibility, embolization success, biodegradability, reperfusion, and biocompatibility of biodegradable microspheres (MS) made from polydioxanone (PDO) for transcatheter arterial embolization.Materials and MethodsUnilateral selective renal embolization of a segmental artery was performed in 16 New Zealand White rabbits with PDO-MS (100–150 μm and 90–315 μm). Animals were randomly assigned to different observation periods and underwent control digital subtraction angiography (DSA) and MR imaging immediately (n = 3), 1 week (n = 2), 4 weeks (n = 2), 8 weeks (n = 2), 12 weeks (n = 5), and 16 weeks (n = 2) after embolization. Kidneys were harvested for macroscopic and histologic analysis of embolization success, biodegradability, and biocompatibility.ResultsEmbolization was technically successful in 15 of 16 animals. One animal died of anesthesia-related circulatory failure. The 100–150 μm MS were injected easily through 3-F catheters; the 90–315 μm MS tended to clog with intermittent catheter obstruction. DSA and MR imaging showed successful target embolization in 13 of 15 animals. In 2 animals, the entire kidney was affected owing to catheter clogging, including a reflux of MS while flushing. Control DSA and MR imaging showed increasing vascular reperfusion with time. Macroscopic and histologic analysis revealed necrosis/infarction in areas in which embolization was achieved. MS were extensively degraded after 16 weeks, and overall inflammatory reaction was mild.ConclusionsBiodegradable PDO-MS induced effective embolization of target vessels while demonstrating good biocompatibility. MS increasingly dissolved at 16 weeks, partial reperfusion started at week 1, and complete reperfusion started at week 8, thus offering possible advantages as a temporary embolic agent.     

Angiographic Revascularization after Bariatric Embolization in a Swine Model

This study evaluated fundal arteriole angiographic revascularization after embolization with embolic microspheres of 3 different diameters in a swine model (16 swine, 31 arterioles). In the 50-μm group, 7 of 11 (64%) arterioles recanalized completely, 3 of 11 (27%) arterioles recanalized partially, and 1 of 11 (9%) arterioles had collateralization (no recanalization). In the 100- to 300-μm group, 7 of 10 (70%) arterioles recanalized completely and 3 of 10 (30%) arterioles) recanalized partially. In the 300- to 500-μm group, 7 of 10 (70%) arterioles recanalized completely, 1 of 10 (10%) arterioles recanalized partially, and 2 of 10 (20%) arterioles had collateralization. No difference was found between the groups in the degree of recanalization (P = .64). All embolized arterioles exhibited some degree of angiographic revascularization, irrespective of the microsphere size.     

Preoperative Transarterial Embolization of Advanced Juvenile Nasopharyngeal Angiofibroma Using n-Butyl Cyanoacrylate: Case-Control Comparison with Microspheres

PurposeTo evaluate the efficacy and safety of transarterial embolization (TAE) with n-butyl cyanoacrylate (nBCA) for juvenile nasopharyngeal angiofibroma (JNA).Materials and MethodsA retrospective review was performed on patients with JNA who underwent TAE and endoscopic resection between 2020 and 2022. Patients embolized with nBCA were identified, and those embolized with microspheres were set as the control group. Data on demographics, symptoms, tumor characteristics, blood loss, adverse events, residual disease, and recurrence were collected, and case-control analysis was performed for the 2 groups. Differences in characteristics between the groups were tested using the Fisher exact and Wilcoxon tests. A generalized linear model (GLM) was used to analyze the univariate and multivariate influences on blood loss.ResultsTwenty patients were included in this study: 13 in the microsphere group and 7 in the nBCA group. The median blood loss was 400 mL (interquartile range [IQR], 200–520 mL) in the nBCA group and 1,000 mL (IQR, 500–1,000 mL) in the microsphere group (P = .028). The GLM confirmed lower blood loss in the nBCA group (relative risk, 0.58 [0.41–0.83]; P = .01). A residual tumor was found in 1 patient in each group (7.7% vs 14.3%; P = 1.000). Recurrence was not observed in any patient. None of the patients experienced adverse events during embolization.ConclusionsTAE of advanced JNA with nBCA glue is safe and effective and can significantly reduce intraoperative blood loss compared with microspheres.     

Prostatic Artery Embolization for Benign Prostatic Hyperplasia: Bleomycin-Eluting versus Bland Microspheres in a Canine Model

PurposeTo prospectively assess safety and efficacy of prostatic artery embolization (PAE) with bleomycin-eluting microspheres for benign prostatic hyperplasia (BPH) in a canine model.Materials and MethodsTwelve adult male beagles (mean age, 1.6 y ± 0.2; range, 1.2–2.0 y) were randomly assigned to group A (n = 6; PAE with bleomycin-eluting 30–60-μm HepaSphere microspheres) and group B (n = 6; PAE with bland 30–60-μm HepaSphere microspheres) between April 2017 and November 2018. Plasma bleomycin concentration in group A was measured within 7 days. Prostate volume (PV) and ischemic volume after PAE were measured by magnetic resonance imaging. Prostates and adjacent organs were harvested after the last magnetic resonance study and histopathologically examined.ResultsPlasma bleomycin concentration peaked at 10 minutes at 2,055.0 ng/mL ± 606.1 and lasted for 1,440 min at low levels after PAE. PV reduction percentage was greater in group A than in group B at 1 month (74.1% ± 4.3 vs 63.7% ± 3.5; P = .006) and 3 months (61.5% ± 6.7 vs 46.1% ± 3.8; P = .001) after PAE. Proportion of prostate ischemic volume was greater in group A than in group B (75.3% ± 3.0 vs 62.0% ± 7.1; P = .006) at 1 month after PAE. Proportion of prostate ischemic volume at 1 month positively correlated with PV percentage reduction at 3 months in group A (r = 0.840, P = .036) and group B (r = 0.844, P = .035). There were no complications or nontarget embolization to surrounding organs after the procedures.ConclusionsIn a canine model, PAE with bleomycin-eluting microspheres was feasible and well tolerated and caused ischemic necrosis and reduction in PV.     

Inline Balloon Occlusion–Assisted Delivery of Ethylene Vinyl Alcohol Copolymer for Peripheral Arterial Applications: A Multicenter Case Series

PurposeTo assess the feasibility, safety, and efficacy of balloon-assisted delivery of ethylene vinyl alcohol copolymer (EVOH) for a range of peripheral arterial applications.Materials and MethodsSix academic medical centers entered retrospective data on 46 consecutive patients (27 men, 19 women; ages, 11–94 y; mean age, 50.3 y) who underwent 60 balloon-assisted EVOH procedures. The cohort was restricted to procedures involving peripheral, nonneural arteries 1–5.5 mm in diameter. Clinical indications included a wide range of vascular pathologic conditions (most commonly arteriovenous malformations [n = 20], renal angiomyolipomas [n = 8], and acute hemorrhage [n = 9]) and targeted visceral and musculoskeletal peripheral arteries. Data collected included sex, age, clinical indication, arterial pathology, arteries embolized, type of occlusion balloon microcatheter, type and concentration of EVOH agent, effectiveness as an embolic backstop, vessels protected, adequacy of EVOH cast penetration, catheter extraction, nontarget embolization, and complications.ResultsBalloon occlusion prevented EVOH reflux in 59 of 60 procedures (98.3%). Nontarget EVOH embolization occurred in 2 procedures (3.3%). Adequate EVOH cast penetration and complete filling of the target pathologic structure were seen in 57 of 60 procedures (95%). Balloon deflation and uneventful extraction occurred in all procedures; small EVOH fragments detached into target arteries in 2 cases. One major (1.7%) and 2 minor (3.3%) complications occurred.ConclusionsBalloon-assisted EVOH embolization of peripheral arteries is feasible, safe, effective, and versatile. The primary advantage of balloon-assisted EVOH embolization is the ability to apply more injection pressure to advance the EVOH cast assertively into the pathologic structure(s).     

Local,Downstream, and Systemic Evaluation after Femoral Artery Angioplasty with Kanshas Drug-Coated Balloons In Vitro and in a Healthy Swine Model

PurposeTo evaluate the incidence of distal embolism and local vascular responses after treatment with the Kanshas drug-coated balloon (DCB) in a preclinical model.Materials and MethodsA total of 90 femoral arteries from 35 healthy swine were treated with a single-dose (×1) or triple-dose (×3) Kanshas DCB that applies the Unicoat technology with 3.2 μg/mm² of paclitaxel. An uncoated Kanshas balloon was used as a control. The arterial wall, downstream skeletal muscle, and nontarget organs (kidneys, lungs, lymph nodes, liver, spleen, and heart) were histologically evaluated. For pharmacokinetic evaluation, a total of 40 healthy swine were treated with ×1 Kanshas DCB, and treated vessels were evaluated ex vivo with high-performance liquid chromatography-mass spectrometry.ResultsArteries treated with the Kanshas DCB showed mild proteoglycan deposition accompanied by the loss of smooth muscle cells (SMCs). These changes increased in a dose-dependent manner (medial SMC loss at 28 days in the ×1 vs ×3 groups, in depth, 1 (0.75–1.38) vs 2 (1.63–2.44); P = .0008; in circumference, 0.83 (0.67–1) vs 1.5 (1.19–1.81); P = .0071). No evidence of distal embolization in skeletal muscles (0 of 210 histological sections) and nontarget organs (0 of 345 sections) was observed. The pharmacokinetic evaluation showed high paclitaxel concentration in the treated artery (912 ng/mg, peaking at 3 minutes), which remained detectable at up to 180 days (0.04 ng/mg).ConclusionsThe Kanshas DCB showed a local drug effect in treated arteries up to 180 days with a high concentration of paclitaxel and no histological evidence of distal embolization.     

Strain Ultrasound Elastography of Aneurysm Sac Content after Randomized Endoleak Embolization with Sclerosing vs. Non-sclerosing Chitosan-based Hydrogels in a Canine Model

PurposeTo compare the mechanical properties of aneurysm content after endoleak embolization with a chitosan hydrogel (CH) with that with a chitosan hydrogel with sodium tetradecyl sulfate (CH-STS) using strain ultrasound elastography (SUE).Materials and MethodsBilateral common iliac artery type Ia endoleaks were created in 9 dogs. Per animal, 1 endoleak was randomized to blinded embolization with CH, and the other, with CH-STS. Brightness-mode ultrasound, Doppler ultrasound, SUE radiofrequency ultrasound, and computed tomography were performed for up to 6 months until sacrifice. Radiologic and histopathologic studies were coregistered to identify 3 regions of interest: the embolic agent, intraluminal thrombus (ILT), and aneurysm sac. SUE segmentations were performed by 2 blinded independent observers. The maximum axial strain (MAS) was the primary outcome. Statistical analysis was performed using the Fisher exact test, multivariable linear mixed-effects models, and intraclass correlation coefficients (ICCs).ResultsResidual endoleaks were identified in 7 of 9 (78%) and 4 of 9 (44%) aneurysms embolized with CH and CH-STS, respectively (P = .3348). CH-STS had a 66% lower MAS (P < .001) than CH. The ILT had a 37% lower MAS (P = .01) than CH and a 77% greater MAS (P = .079) than CH-STS. There was no significant difference in ILT between treatments. The aneurysm sacs embolized with CH-STS had a 29% lower MAS (P < .001) than those embolized with CH. Residual endoleak was associated with a 53% greater MAS (P < .001). The ICC for MAS was 0.807 (95% confidence interval: 0.754–0.849) between segmentations.ConclusionsCH-STS confers stiffer intraluminal properties to embolized aneurysms. Persistent endoleaks are associated with increased sac strain, an observation that may help guide management.     

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

PurposeTo 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 MethodsFifty-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.ResultsThe 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).ConclusionsThe 15–19-μm embolic agents were the most favorable for causing tumor necrosis without nontarget toxicity in the transarterial treatments of rat HCC models.     

Comparison of Bolus Versus Dual-Syringe Administration Systems on Glass Yttrium-90 Microsphere Deposition in an In Vitro Microvascular Hepatic Tumor Model

PurposeTo utilize an in vitro microvascular hepatic tumor model to compare the deposition characteristics of glass yttrium-90 microspheres using the dual-syringe (DS) and traditional bolus administration methods.Materials and MethodsThe microvascular tumor model represented a 3.5-cm tumor in a 1,400-cm³ liver with a total hepatic flow of 160 mL/min and was dynamically perfused. A microcatheter was placed in a 2-mm artery feeding the tumor model and 2 additional nontarget arteries. Glass microspheres with a diameter of 20–30 μm were administered using 2 methods: (a) DS delivery at a concentration of 50 mg/mL in either a single, continuous 2-mL infusion or two 1-mL infusions and (b) bolus delivery (BD) of 100 mg of microspheres in a single 3-mL infusion.ResultsOverall, the degree of on-target deposition of the microspheres was 85% ± 11%, with no significant differences between the administration methods. Although the distal penetration into the tumor arterioles was approximately 15 mm (from the second microvascular bifurcation of the tumor model) for all the cases, the distal peak particle counts were significantly higher for the DS delivery case (approximately 5 × 10⁵ microspheres achieving distal deposition vs 2 × 10⁵ for the BD case). This resulted in significantly higher deposition uniformity within the tumor model (90% for the DS delivery case vs 80% for the BD case, α = 0.05).ConclusionsThe use of this new in vitro microvascular hepatic tumor model demonstrated that the administration method can affect the deposition of yttrium-90 microspheres within a tumor, with greater distal deposition and more uniform tumor coverage when the microspheres are delivered at consistent concentrations using a DS delivery device. The BD administration method was associated with less favorable deposition characteristics of the microspheres.     

Angiographic Findings during Repeat Prostatic Artery Embolization

PurposeTo describe mechanisms of prostate revascularization based on imaging findings during repeat prostatic artery embolization (PAE; rPAE).Materials and MethodsThis is a retrospective analysis of 10 rPAEs performed between October 2012 and September 2018 in patients with recurrent lower urinary tract symptoms (LUTS) after PAE (mean age, 68.2 y ± 4.5). Two interventional radiologists reviewed PAE and rPAE images and defined 6 patterns of revascularization. Correlation between embolization of the posterolateral (PL) prostatic branch during previous PAE and prostate revascularization on rPAE was assessed by Fisher exact test. One hemiprostate was excluded because no detectable revascularization was observed.ResultsAll patients showed LUTS improvement after previous PAEs (P < .01 for 5 outcome measures) and had recurrence during follow-up. rPAEs were performed a mean of 40.9 months after previous PAEs (18–96 mo). Of 19 hemiprostates analyzed, 11 presented revascularization by 2 or more branches (57.9%). The PL branch (29.0%) and the recanalized main prostatic artery (25.8%) were the most frequent revascularizing branches observed, followed by distal branches of obturator (12.9%), internal pudendal (12.9%), superior vesical (12.9%), and contralateral arteries (6.5%). Embolization of the PL branch during previous PAE significantly reduced the incidence of revascularization by this branch (P = .002).ConclusionsMechanisms of revascularization in rPAE are diverse and complex. Revascularization by the PL branch and recanalization of the previously embolized prostatic artery were the most frequent patterns observed. Embolization of the PL branch may reduce the incidence of prostate revascularization and LUTS recurrence after PAE.     

Superior Rectal Artery Embolization with Tris-Acryl Gelatin Microspheres: A Randomized Comparison of Particle Size

PurposeTo evaluate the safety and efficacy of superior rectal artery embolization (SRAE) with different-sized tris-acryl gelatin microspheres in symptomatic hemorrhoidal disease (HD).Materials and MethodsForty-two patients (male, 30; female, 12; median age, 45 years) with symptomatic HD (2 grade I, 8 grade II, 17 grade III, and 15 grade IV) were divided into 3 experimental arms (500–700 μm, 700–900 μm, and 900–1,200 μm groups; each had 14 patients) in a prospective randomized style to perform SRAE. Follow-up was performed by rectoscopy, clinical examination, and questionnaires. The primary outcome measure was the clinical success rate at 12 months. Secondary outcome measures were technical success rate, recurrence rate, procedure-related mortality, procedure-related complications, and any outcome changes between particle sizes.ResultsNo procedure-related deaths or major morbidities were observed. There was a 54% minor complication rate (n = 23/42) in the treated zone: 45% sustained small superficial ulcerations (n = 19/42), 7% small rectosigmoid junction ulcerations (n = 3/42), and 2% small fibrotic scar tissue (n = 1/42). The clinical success rate was 93%. Of the groups, the best French bleeding score decrease was obtained in the 900–1,200 μm group. There were improvements in the quality of life score and visual analogue scale score after the SRAE procedure, although not in the Goligher score. No recurrent disease was observed.ConclusionsSRAE with tris-acryl gelatin microspheres for symptomatic HD is a safe and efficient treatment, with results favoring the use of larger microspheres.     

Outcomes of Hemorrhoidal Artery Embolization from a Multidisciplinary Outpatient Interventional Center

PurposeTo evaluate the safety and efficacy of outpatient transarterial embolization for symptomatic refractory internal hemorrhoids.Materials and MethodsRetrospective analysis of 134 patients who underwent hemorrhoidal artery embolization (HAE) for symptomatic internal hemorrhoids between August 2021 and June 2022 (76 men and 58 women) was performed. The mean age was 54.9 years, with a mean Goligher hemorrhoid grade (HG) of 2.1. Branches of the superior rectal artery (SRA) or middle rectal artery supplying the corpus cavernosum recti were embolized with both spherical particles and microcoils. Standard-of-care evaluations were performed at baseline and the 1 month follow-up, which included hemorrhoid-related pain (HRP) (0–10), hemorrhoid symptoms score (HSS) (5–20), quality of life (QoL) (0–4), French bleeding score (FBS) (0–9), and HG (0–4). Clinical success was defined as improvement of symptoms without additional treatment.ResultsEmbolization of at least 1 hemorrhoidal artery was achieved in 133 (99%) of the 134 patients. The mean number of SRA branches embolized per patient was 2.9 ± 1.0. Clinical success was seen in 93% (124 of 134) of patients at the 1-month follow-up, with 10 patients requiring repeat embolization. There were significant improvements in all mean outcomes at 1 month: HSS (11–7.8; P < .01), HRP (4.1–1.3; P < .01), QoL (2.2–0.8; P < .01), FBS (4.4–2.2; P < .01), and HG (2.3–1.2; P < .05). There were no severe adverse events.ConclusionsHAE is a safe and effective outpatient treatment for refractory symptomatic internal hemorrhoids in the short term.     

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.     

Impact of Chemoembolic Regimen on Immune Cell Recruitment and Immune Checkpoint Marker Expression following Transcatheter Arterial Chemoembolization in a VX2 Rabbit Liver Tumor Model

PurposeTo characterize the effects of commonly used transcatheter arterial chemoembolization (TACE) regimens on the immune response and immune checkpoint marker expression using a VX2 rabbit liver tumor model.Materials and MethodsTwenty-four VX2 liver tumor-bearing New Zealand white rabbits were assigned to 7 groups (n = 3 per group) undergoing locoregional therapy as follows: (a) bicarbonate infusion without embolization, (b) conventional TACE (cTACE) using a water-in-oil emulsion containing doxorubicin mixed 1:2 with Lipiodol, drug-eluting embolic-TACE with either (c) idarubicin-eluting Oncozene microspheres (40 μm) or (d) doxorubicin-eluting Lumi beads (40–90 μm). For each therapy arm (b–d), a tandem set of 3 animals with additional bicarbonate infusion before TACE was added, to evaluate the effect of pH modification on the immune response. Three untreated rabbits served as controls. Tissue was harvested 24 hours after treatment, followed by digital immunohistochemistry quantification (counts/μm² ± SEM) of tumor-infiltrating cluster of differentiation 3⁺ T-lymphocytes, human leukocyte antigen DR type antigen-presenting cells (APCs), cytotoxic T-lymphocyte–associated protein-4 (CTLA-4), and programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway axis expression.ResultsLumi-bead TACE induced significantly more intratumoral T-cell and APC infiltration than cTACE and Oncozene-microsphere TACE. Additionally, tumors treated with Lumi-bead TACE expressed significantly higher intratumoral immune checkpoint markers compared with cTACE and Oncozene-microsphere TACE. Neoadjuvant bicarbonate demonstrated the most pronounced effect on cTACE and resulted in a significant increase in intratumoral cluster of differentiation 3⁺ T-cell infiltration compared with cTACE alone.ConclusionsThis preclinical study revealed significant differences in evoked tumor immunogenicity depending on the choice of chemoembolic regimen for TACE.     

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.     

Transarterial Embolization of Liver Cancer in a Transgenic Pig Model

PurposeTo develop and characterize a porcine model of liver cancer that could be used to test new locoregional therapies.Materials and MethodsLiver tumors were induced in 18 Oncopigs (transgenic pigs with Cre-inducible TP53^R167H and KRAS^G12D mutations) by using an adenoviral vector encoding the Cre-recombinase gene. The resulting 60 tumors were characterized on multiphase contrast-enhanced CT, angiography, perfusion, micro-CT, and necropsy. Transarterial embolization was performed using 40–120 μm (4 pigs) or 100–300 μm (4 pigs) Embosphere microspheres. Response to embolization was evaluated on imaging. Complications were determined based on daily clinical evaluation, laboratory results, imaging, and necropsy.ResultsLiver tumors developed at 60/70 (86%) inoculated sites. Mean tumor size was 2.1 cm (range, 0.3–4 cm) at 1 week. Microscopically, all animals developed poorly differentiated to undifferentiated carcinomas accompanied by a major inflammatory component, which resembled undifferentiated carcinomas of the human pancreatobiliary tract. Cytokeratin and vimentin expression confirmed epithelioid and mesenchymal differentiation, respectively. Lymph node, lung, and peritoneal metastases were seen in some cases. On multiphase CT, all tumors had a hypovascular center, and 17/60 (28%) had a hypervascular rim. After transarterial embolization, noncontrast CT showed retained contrast medium in the tumors. Follow-up contrast-enhanced scan showed reduced size of tumors after embolization using either 40–120 μm or 100–300 μm Embosphere microspheres, while untreated tumors showed continued growth.ConclusionsLiver tumors can be induced in a transgenic pig and can be successfully treated using bland embolization.     

Retrospective Comparison of Pulmonary Arteriovenous Malformation Embolization with the Polytetrafluoroethylene-Covered Nitinol Microvascular Plug,AMPLATZER Plug,and Coils in Patients with Hereditary Hemorrhagic Telangiectasia

PurposeTo evaluate effectiveness of the polytetrafluoroethylene-covered nitinol mesh microvascular plug (MVP) and compare it with other devices in pulmonary arteriovenous malformation (PAVM) embolization in patients with hereditary hemorrhagic telangiectasia (HHT).Materials and MethodsTwenty-five patients (average age 35 y; range, 15–56 y) with hereditary hemorrhagic telangiectasia (HHT) and de novo PAVM embolization with at least 1 MVP between November 2015 and May 2017 were retrospectively evaluated. Retrospective data were also obtained from prior embolization procedures in the same patient population with other embolic devices dating back to 2008. Technical success, complications, PAVM persistence rates, and category of persistence were analyzed.ResultsIn 25 patients, 157 PAVMs were treated: 92 with MVP, 35 with AMPLATZER vascular plug (AVP), 6 with AVP plus coils, and 24 with coils. The per-PAVM technical success rates were 100% with MVP; 97%, AVP; 100%, AVP plus coils; and 100%, coils. PAVM persistence rates and median follow-up were as follows: MVP, 2% (1/92) (510 d); AVP, 15% (3/20) (1,447 d); AVP plus coils, 20% (1/5) (1,141 d); coils, 46.7% (7/15) (1,141 d). Persistence owing to recanalization for MVP, AVP, AVP plus coils, and coils was 2%, 15%, 0%, and 33%. No difference was found between persistence rates of MVP vs AVP (P = .098). Embolization with a vascular plug (MVP or AVP) with or without coils had a statistically significant lower persistence rate (5.4%) than embolization with coils alone (46.7%) (P = .022).ConclusionsPAVM embolization with MVP had a high technical success rate and a low persistence rate comparable to AVP and lower than coil embolization alone.     

Iatrogenic Renal Artery Injury in 90 Cases: Arteriographic Findings and Outcomes after Embolization for Bleeding

PurposeTo evaluate differences in arteriographic findings and outcomes after embolization among patients with a suspected iatrogenic renal arterial injury (IRAI).Materials and MethodsPatients at the authors’ institution who underwent renal arteriography for suspected IRAIs after partial nephrectomy, biopsy, or percutaneous access over a 20-year period were included. Records, imaging, and outcomes were reviewed. Data analysis was performed using the Fisher exact or Kruskal-Wallis test.ResultsNinety arteriograms were performed on 83 patients after partial nephrectomy (n = 32), biopsy (n = 27), or percutaneous access (n = 24), including for nephrostomy/ureterostomy and stone removal. The median number of days between the index procedure and arteriogram was highest (15 days) after partial nephrectomy and lowest (5 days) after biopsy (P = .0001). Embolization was performed during 76% of arteriograms. If prearteriographic imaging showed positive results for IRAIs, embolization was performed in 67% versus 33% if imaging showed negative results (P = .005). The transfusion rate was higher after biopsy than after partial nephrectomy or percutaneous access (P = .002). Acute kidney injury after arteriogram occurred in 7% of patients; however, all returned to baseline by 1 week.ConclusionsDespite the different mechanism of IRAIs in partial nephrectomy, biopsy, and percutaneous access, arteriographic findings and outcomes were overall similar among groups. Prearteriographic imaging can help identify IRAIs but cannot supersede the clinical judgment regarding indication for embolization. IRAIs can present acutely or after a long interim, although patients who underwent biopsy presented earlier and more frequently required a blood transfusion. IRAIs can be treated with embolization without permanent deleterious effects on renal function.