Intra-arterial Administration Research Articles

Intra-arterial tenecteplase during thrombectomy for acute stroke (BRETIS-TNK II): rationale and design

BackgroundOur recent pilot study suggests intra-arterial tenecteplase (TNK) during the first pass of endovascular treatment (EVT) seems safe, may increase first-pass reperfusion and good outcome in acute ischaemic stroke (AIS)...

Interventional Treatment Strategies in Intrahepatic Cholangiocarcinoma and Perspectives for Combined Hepatocellular-Cholangiocarcinoma.

cHCC-CCA is an uncommon type of liver cancer that exhibits clinical and pathological characteristics of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), which are the two main forms of primary liver cancer. The similarity to HCC and CCA makes therapeutical strategies challenging. The poor prognosis of CCA in general, as well as for cHCC-CCA, is mainly attributable to the fact that diagnosis is often at an advanced stage of disease. During the last decade, locoregional therapies usually performed by interventional radiologists and its established role in HCC treatment have gained an increasing role in CCA treatment as well. These comprise a wide range of options from tumor ablation procedures such as radiofrequency ablation (RFA), microwave ablation (MWA), computed tomography high-dose rate brachytherapy (CT-HDRBT), and cryoablation to transarterial chemoembolization (TACE), including the option of intra-arterial administration of radioactive spheres (transarterial radioembolization-TARE), and much attention has focused on the potential of individual concepts in recent years. The purpose of this review is to provide an overview of current radiologic interventions for CCA (excluding options for eCCA), to review and appraise the existing literature on the topic, and to provide an outlook on whether such interventions may have a role as treatment for cHCC-CCA in the future.

Preclinical validation of a novel therapeutic strategy for choroid plexus carcinoma

Choroid plexus carcinoma (CPC) is a rare infantile brain tumor with an aggressive clinical course that often leaves children with debilitating side effects due to aggressive and toxic chemotherapies. Development of novel therapeutical strategies for this disease have been extremely limited owing to the rarity of the disease and the paucity of biologically relevant substrates. We conducted the first high-throughput screen (HTS) on a human patient-derived CPC cell line (Children Cancer Hospital Egypt, CCHE-45) and identified 427 top hits highlighting key molecular targets in CPC. Furthermore, a combination screen with a wide variety of targets revealed multiple synergistic combinations that may pave the way for novel therapeutical strategies against CPC. Based on in vitro efficiency, central nervous system (CNS) penetrance ability and feasible translational potential, two combinations using a DNA alkylating or topoisomerase inhibitors in combination with an ataxia telangiectasia mutated and rad3 (ATR) inhibitor (topotecan/elimusertib and melphalan/elimusertib respectively) were validated in vitro and in vivo. Pharmacokinetic assays established increased brain penetrance with intra-arterial (IA) delivery over intra-venous (IV) delivery and demonstrated a higher CNS penetrance for the combination melphalan/elimusertib. The mechanisms of synergistic activity for melphalan/elimusertib were assessed through transcriptome analyses and showed dysregulation of key oncogenic pathways (e.g. MYC, mammalian target of rapamycin mTOR, p53) and activation of critical biological processes (e.g. DNA repair, apoptosis, hypoxia, interferon gamma). Importantly, IA administration of melphalan combined with elimusertib led to a significant increase in survival in a CPC genetic mouse model. In conclusion, this study is, to the best of our knowledge, the first that identifies multiple promising combinatorial therapeutics for CPC and emphasizes the potential of IA delivery for the treatment of CPC.

Case Series of Precision Delivery of Methylprednisolone in Pediatric Inflammatory Bowel Disease: Feasibility, Clinical Outcomes, and Identification of a Vasculitic Transcriptional Program

Systemic steroid exposure, while useful for the treatment of acute flares in inflammatory bowel disease (IBD), is associated with an array of side effects that are particularly significant in children. Technical advancements have enabled locoregional intraarterial steroid delivery directly into specific segments of the gastrointestinal tract, thereby maximizing tissue concentration while limiting systemic exposure. We investigated the feasibility of intraarterial steroid administration into the bowel in a cohort of nine pediatric patients who had IBD. This treatment approach provided symptom relief in all patients, with sustained relief (>2 weeks) in seven out of nine; no serious adverse effects occurred in any patient. In addition, we identified patterns of vascular morphologic changes indicative of a vasculopathy within the mesenteric circulation of inflamed segments of the bowel in pediatric patients with Crohn's disease, which correlated with disease activity. An analysis of publicly available transcriptomic studies identified vasculitis-associated molecular pathways activated in the endothelial cells of patients with active Crohn's disease, suggesting a possible shared transcriptional program between vasculitis and IBD. Intraarterial corticosteroid treatment is safe and has the potential to be widely accepted as a locoregional approach for therapy delivery directly into the bowel; however, this approach still warrants further consideration as a short-term "bridge" between therapy transitions for symptomatic IBD patients with refractory disease, as part of a broader steroid-minimizing treatment strategy.

Abstract Number ‐ 69: Intrathecal Nicardipine for Severe Intractable Reversible Cerebral Vasoconstriction Syndrome (RCVS): A Novel Case Report

Introduction Reversible Cerebral Vasoconstriction Syndrome (RCVS) is a poorly understood but increasingly recognized entity, likely multifactorial in nature and characterized by diffuse cerebral vasospasm that present as sudden, intense, fluctuating headaches. A subset of RCVS patients can present with concomitant TIAs, cerebral infarctions, leukoencephalopathy, subarachnoid hemorrhages (SAH), and seizures. Due to insufficient evidence, there is currently no consensus on RCVS treatment guidelines. Calcium channel blockers such as nimodipine and verapamil have reportedly been employed with varying degrees of efficacy. Nicardipine, an L‐type calcium channel blocker, may prove effective in RCVS treatment because of its ability to penetrate the blood‐brain barrier. However, to date, only 5 case reports have discussed the use of intrathecal (IT) nicardipine for the treatment of severe RCVS, and there has been very limited exploration of continuous intraarterial (IA) administration. This case report examines the use of IT and continuous IA nicardipine in an RCVS patient refractory to traditional management. Methods We present the case of a 58‐year‐old female who was noted to have a non‐traumatic non‐aneurysmal SAH secondary to RCVS. The patient’s only risk factor for RCVS was alcoholic use. Initially managed with oral verapamil, she later developed refractory symptomatic vasoconstriction requiring multiple angiograms for spasmolysis via balloon angioplasty and IA nicardipine. Due to the refractory nature of her spasm despite the IA therapy, we decided to attempt intrathecal nicardipine, starting at 4 mg q12hours via an external ventricular drain (EVD). This dose was escalated to 4mg q6hours. The patient stabilized for 24 hours but again decompensated, requiring continuous IA spasmolysis via a microcatheter that was placed in the L MCA and left for continuous IA nicardipine infusion (5mg/hr). The patient showed slow incremental improvement clinically and a decrease in vasospasms on imaging, ultimately suffering minimal stroke burden. Results The patient subsequently showed improvement over time in neurological function and a decrease in vasospasms on CTA, MRA, and angiogram imaging, ultimately suffering minimal stroke burden (Fig. 1B). Conclusions Nicardipine, administered intrathecally utilizing an EVD or even intraarterial through a microcatheter, could potentially be beneficial in select patients with refractory RCVS to minimize repeat angiography/angioplasty. We suggest further studies to determine SAH incidence following RCVS and the efficacy of continuous intrathecal administration of the blood‐brain barrier penetrating calcium channel blocker, nicardipine, in RCVS patients.

Exploring Intra-arterial Contrast Administration for Intraoperative Imaging Using a Swine Model.

Intraoperative computed tomography (CT) imaging with endovascular delivery of intra-arterial (IA) contrast could potentially provide higher attenuation with lower contrast volumes than intravenous (IV) administration. We aimed to compare IA and IV contrast use for organ-specific CT abdominal imaging. Five anesthetized swine had external jugular and brachial artery access with ascending aortic pigtail placement. An IV protocol was 100mL at 5mL/sec over 20 sec vs 50mL of IA contrast at 5mL/sec over 10 sec. Region-of-interest markers were applied to anatomical regions to measure attenuation (HU) over time. IA and IV contrast protocols achieved adequate aortic opacification (IA, 455 ± 289 vs IV, 450 ± 114 HU). The IA contrast aortic attenuation curve reached peak attenuation compared with IV contrast (IA, 8 vs 23 sec; P < .001). Time to peak attenuation was similar between IA and IV contrast in the portal vein (IA, 38 vs IV, 42 sec, P = .25). IA administration achieved a superior contrast-to-noise ratio (CNR) in less time compared with IV (R2 = .94; P < .001). IA contrast achieved adequate opacification with less bolus broadening and a superior CNR compared with IV contrast while using a smaller contrast volume for directed organ-directed imaging.

Predictive factors for improvement of symptomatic cerebral vasospasm following subarachnoid hemorrhage by selective intra-arterial administration of fasudil hydrochloride.

Symptomatic cerebral vasospasm after subarachnoid hemorrhage (SAH) is a significant cause of delayed cerebral ischemia that leads to poor outcomes. Selective intra-arterial administration of fasudil hydrochloride (IAF) has been adopted for its vasodilatory effect on spasm arteries to prevent delayed cerebral ischemia. However, its effect on clinical outcomes and predictive factors for good recovery are not fully understood. This study aimed to investigate the outcomes of selective IAF and identify predictive factors for good outcomes in patients with cerebral vasospasm after SAH. A retrospective study of 36 patients with cerebral vasospasm following SAH who underwent selective IAF at our institution between January 2014 and May 2022 was conducted. We evaluated the improvements in neurological findings before and after selective IAF. Statistical analyses were performed to determine factors associated with good outcomes. Selective IAF improved the neurological findings in 26 patients (72.2%). Pre-therapeutic absence of cerebral infarction in more than 1/3 of the spasm artery perfusion area was significantly associated with an improvement in neurological findings (p < 0.0001). Furthermore, there was a tendency for a good outcome when the age was younger (p = 0.093), and the spasm was limited to peripheral vessels (p = 0.065). Our study indicates that selective IAF has a promising effect in improving symptomatic vasospasm, except when a large cerebral infarction exists in the spasm artery perfusion area. Early consideration of selective IAF could be recommended once patients experience symptomatic cerebral vasospasm after SAH.

Targeted Therapy for Glomerulonephritis Using Arterial Delivery of Encapsulated Etanercept.

Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonephritis to help them overcome symptoms and prevent chronic renal failure. Such an approach requires long-term systemic administration of strong medications, which causes severe side effects. This work shows the efficiency of polymer capsule accumulation (2.8 ± 0.4 µm) containing labeled etanercept (100 μg per dose) in the kidneys of mice. The comparison of injection into the renal artery and tail vein shows the significant superiority of the intra-arterial administration strategy. The etanercept retention rate of 18% and 8% ID in kidneys was found 1 min and 1 h after injection, respectively. The capsules were predominantly localized in the glomeruli after injection in mice using a model of acute glomerulonephritis. Histological analysis confirmed a significant therapeutic effect only in animals with intra-arterial administration of microcapsules with etanercept. The proposed strategy combines endovascular surgery and the use of polymer microcapsules containing a high molecular weight drug that can be successfully applied to treat a wide range of kidney diseases associated with glomerular pathology.

Effect of β3-adrenoceptor agonist on the micromotion of bilateral major pelvic ganglion-excised rat bladder.

Micromotion is an autonomous intramural movement of the bladder, and is believed to be an initial step in the generation of urinary urgency. Therefore, controlling micromotion may be a novel target in overactive bladder (OAB) treatment. However, developing micromotion treatment has been limited by the absence of a standardized animal model. We attempted to create a micromotion animal model and investigated the effectiveness of a β3 -adrenoceptor agonist (CL316,243) on micromotion. Bilateral major pelvic ganglia (MPGs) were excised in 18 male Sprague-Dawley rats, resulting in an almost completely denervated bladder. On postoperative Day 7, cystometry was performed. Rats were divided into three treatment groups: CL316,243; β3- adrenoceptor antagonist (SR59230A) pretreated CL316,243; and a nonselective antimuscarinic agent (oxybutynin). Changes in micromotion were evaluated after the intra-arterial administration of each agent. Low-amplitude oscillations in intravesical pressure (micromotion) were observed 1 week after MPGs excision. Micromotion frequency significantly (p = 0.003) decreased (2.17 ± 3.54 times/5 min) with CL316,243 compared with vehicle (6.33 ± 1.97 times/5 min). Micromotion amplitude also decreased with CL316,243 (1.15 ± 1.93 cmH2 O) compared with vehicle (5.96 ± 5.12 cmH2 O), approaching conventional significance (p = 0.090). No significant decreases in frequency or amplitude were observed with oxybutynin treatment. Systemic administration of the β3 -adrenoceptor agonist CL316,243 effectively controlled micromotion in bilateral MPGs-excised, almost completely denervated rat bladders. This result indicates that β3 -adrenoceptor agonist may affect the bladder directly, suggesting that it might be effective for overall OAB, regardless of the presence or level of neurological deficits. Bilateral MPGs-excised rats are considered a plausible micromotion animal model suitable for future research.

Efficacy of intra-arterial lidocaine administration on pain and inflammatory response after uterine artery embolization for symptomatic fibroids.

There have been conflicting outcomes regarding the use of lidocaine to reduce pain after uterine artery embolization (UAE). To investigate the efficacy of intra-arterial lidocaine injection for pain and inflammatory response control within 24 h of UAE for symptomatic uterine fibroids. Of 1530 patients who underwent UAE for uterine fibroids in 2007-2021, 5 mL of 1% lidocaine was injected into each uterine artery immediately after UAE in 23 patients. A disease-matched control group (n = 23) who did not receive intra-arterial lidocaine was generated from the same registry. The pain score, white blood cell (WBC) count, C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), and fentanyl consumption were compared before and after UAE. Complete infarction of the dominant fibroid was assessed using magnetic resonance imaging. Significantly lower WBC count, CRP level, and NLR were noted 24 h after UAE in the lidocaine group. No statistically significant difference was noted in the pain score between groups at 0-24 h. The cumulative fentanyl dose administered during the first 24 h after UAE was not significantly different. After embolization, fibroid-related symptoms resolved in all patients. No significant difference was observed in the rate of complete infarction of the dominant fibroid. Lidocaine administration immediately after UAE resulted in a significant reduction in the inflammatory response. However, such a difference in the inflammatory reaction did not contribute to significant reductions in pain scores or fentanyl consumption.

Phenotyping of Macrophages After Radiolabeling and Safety of Intra-arterial Transplantation Assessed by SPECT/CT and MRI.

Cell therapy is an integral modality of regenerative medicine. Macrophages are known for their sensitivity to activation stimuli and capability to recruit other immune cells to the sites of injury and healing. In addition, the route of administration can impact engraftment and efficacy of cell therapy, and modern neuro-interventional techniques provide the possibility for selective intra-arterial (IA) delivery to the central nervous system (CNS) with very low risk. The effects of radiolabelling and catheter transport on differentially activated macrophages were evaluated. Furthermore, the safety of selective IA administration of these macrophages to the rabbit brain was assessed by single-photon emission computed tomography/computed tomography (SPECT/CT) and ultra-high-field (9.4 T) magnetic resonance imaging (MRI). Cells were successfully labeled with (111In)In-(oxinate)3 and passed through a microcatheter with preserved phenotype. No cells were retained in the healthy rabbit brain after IA administration, and no adverse events could be observed either 1 h (n = 6) or 24 h (n = 2) after cell administration. The procedure affected both lipopolysaccharide/gamma interferon (LPS/IFNγ) activated cells and interleukin 4 (IL4), interleukin 10 (IL10)/transforming growth factor beta 1 (TGFβ1) activated cells to some degree. The LPS/IFNγ activated cells had a significant increase in their phagocytotic function. Overall, the major impact on the cell phenotypes was due to the radiolabeling and not passage through the catheter. Unstimulated cells were substantially affected by both radiolabeling and catheter administration and are hence not suited for this procedure, while both activated macrophages retained their initial phenotypes. In conclusion, activated macrophages are suitable candidates for targeted IA administration without adverse effects on normal, healthy brain parenchyma.

Tissue Distribution of Cisplatin by Intra-arterial Infusion Route in Comparison to Systemic Route: Implication to Therapy for Node-positive Bladder Cancer.

In clinical practice, platinum-based systemic chemotherapy works to shrink pelvic lymph nodes. Intra-arterial (IA) bolus infusion may result in more favorable results than systemic chemotherapy. In the present study, we investigated the distribution of cisplatin administrated by IA infusion in varying organs, specifically focusing on the node tissue, in comparison with the intravenous (IV) route. Under anesthesia, cisplatin 0.42 mg/body was administrated by IA or IV infusion in rats to mimic a balloon-occluded arterial infusion model used in clinical practice. The kidney, bladder, lymphatic tissue, and peripheral blood were extracted to analyze the amount of cisplatin by inductively coupled plasma-mass spectrometry. Concertation of cisplatin by IA infusion was higher than that by the IV route in the peripheral blood and kidney. IA infusion led to a significantly high concentration of cisplatin in the bladder compared to IV infusion (1.3±0.452 vs. 0.2 ppb/mg ± 0.055, p=0.050). Furthermore, the IA method led to an extremely high concentration of cisplatin in the lymphatic tissue compared to the IV method (0.1±0.036 vs. 13.3±5.36, p=0.048). High cisplatin accumulation in the lymphatic tissue and bladder by IA administration may have a potential role for treating patients with node-positive bladder cancer.

Последствия случайного внутриартериального введения бициллина — синдром Онэ

The article presents a description of a rare clinical case of consequences of accidental intra-arterial administration of bicillin with the development of Hoigne syndrome.

Contrast-induced acute kidney injury and its contemporary prevention.

The complexity and application range of interventional and diagnostic procedures using contrast media (CM) have recently increased. This allows more patients to undergo procedures that involve CM administration. However, the intrinsic CM toxicity leads to the risk of contrast-induced acute kidney injury (CI-AKI). At present, effective therapy of CI-AKI is rather limited. Effective prevention of CI-AKI therefore becomes crucially important. This review presents an in-depth discussion of CI-AKI incidence, pathogenesis, risk prediction, current preventive strategies, and novel treatment possibilities. The review also discusses the difference between CI-AKI incidence following intraarterial and intravenous CM administration. Factors contributing to the development of CI-AKI are considered in conjunction with the mechanism of acute kidney damage. The need for ultimate risk estimation and the prediction of CI-AKI is stressed. Possibilities of CI-AKI prevention is evaluated within the spectrum of existing preventive measures aimed at reducing kidney injury. In particular, the review discusses intravenous hydration regimes and pre-treatment with statins and N-acetylcysteine. The review further focuses on emerging alternative imaging technologies, alternative intravascular diagnostic and interventional procedures, and new methods for intravenous hydration guidance; it discusses the applicability of those techniques in complex procedures and their feasibility in current practise. We put emphasis on contemporary interventional cardiology imaging methods, with a brief discussion of CI-AKI in non-vascular and non-cardiologic imaging and interventional studies.

Intracoronary versus intraarterial heparin administration during coronary angiography and percutaneous intervention: A three-year experience from Hospital Universiti Sains Malaysia

Vascular access site hematoma is one of the common vascular complications for percutaneous coronary intervention (PCI). We conduct a study for site specific unfractionated heparin (UFH) administration of intracoronary versus intraarterial in relation to vascular access site hematoma.

Neutrophil gelatinase-associated lipocalin monitoring reveals persistent subclinical kidney injury following intraarterial administration of iodinated contrast agents

Clinically overt contrast-induced nephropathy (CIN) is one of the most feared complications in patients exposed to iodinated contrast media and has been extensively studied over the years. Meanwhile, the incidence and evolution of subclinical contrast-induced kidney injury remain elusive. With the continuous increase in the number of patients that are repeatedly exposed to contrast media, elucidating these issues is of critical importance. Accordingly, we aimed to evaluate the incidence and the evolution of clinical and subclinical kidney injury in patients exposed to contrast media. A total of 178 patients who underwent elective percutaneous angioplasty procedures were evaluated prospectively. Serum creatinine and neutrophil gelatinase-associated lipocalin (NGAL) levels were evaluated pre-procedurally, 48 h and 1 month after administration of contrast media. The evolution of creatinine and NGAL levels was analyzed at the three time points, and the potential predictors of contrast-induced clinical and subclinical renal injury were evaluated. Clinically overt CIN occurred in 10 (5.6%) patients. Baseline serum creatinine and the volume of contrast media were the only independent predictors of CIN and in all 10 patients creatinine levels returned to baseline by 1 month (p = 0.32). Subclinical contrast-induced kidney injury was much more common, affecting 32 (17.9%) patients, was only predicted by the baseline serum creatinine, and persisted in 53.1% of patients after 1 month. This study showed that whereas clinically overt CIN is rather rare and regressive, subclinical contrast-induced kidney injury is considerably more frequent, affecting almost 18% of patients that receive intraarterial contrast media. More importantly, subclinical kidney injury persisted after 1 month in more than 50% of the initially affected patients, who may thus be at increased risk for further renal impairment, particularly if exposed to nephrotoxic agents or repeated administration of contrast media.

Abstract 15619: Smoking Towards Prinzmetal

Background: Vasospastic (Prinzmetal) angina is a result of coronary vasospasm leading to myocardial ischemia. It is defined by nitrate responsive angina, transient ischemic ECG changes, and coronary vasospasm. In this report, we highlight coronary angiographic findings of Prinzmetal angina and underscore tobacco use as a known risk factor. Case Presentation: A 62-year-old male with hypertension and tobacco use presented with acute substernal chest pain. Laboratory testing revealed elevated troponin to 17.4 mg/mL and ECG with new T-wave inversions in the lateral leads. Coronary angiogram revealed non-obstructive coronary artery disease (CAD) (Figure 1). He was discharged on medical therapy and instructed to stop smoking. Four days later, he returned with one day of chest pain that improved with sublingual nitroglycerin. Repeat troponin was elevated to 46.9 ng/mL and ECG revealed ST depressions in V2-V6. Repeat coronary angiogram revealed 99% narrowing in the proximal left circumflex (LCx) (Figure 2). Intra-arterial nitroglycerin administration led to resolution of the LCx narrowing (Figure 3). Conclusion: Prinzmetal angina can be precipitated by tobacco use. Clinicians ought to maintain a high degree of suspicion for Prinzmetal angina as an etiology of cardiac ischemia in patients who have non-obstructive CAD and concomitant tobacco use.

The efficacy of nitroglycerin to prevent radial artery spasm and occlusion during and after transradial catheterization: A systematic review and meta-analysis of randomized controlled trials.

Radial artery spasm (RAS) is the most common cause of transradial access site crossover and is a common intra-procedural complication. RAS incidence can lead to radial artery occlusion (RAO) postprocedure, preventing the radial artery as a future access site. We evaluated the efficacy of nitroglycerin preventing RAS and RAO during transradial catheterization discussing the different routes of administration, including topical, subcutaneous, and intra-arterial. A systematic review and meta-analysis included all relevant articles until April 23, 2022. We searched six databases Google Scholar, Web of Science, SCOPUS, EMBASE, PubMed (MEDLINE), and CENTRAL. We registered our review protocol in PROSPERO with ID: CRD42022330356. We included 11 trials with 5814 patients. Compared to placebo, the pooled analysis favored subcutaneous nitroglycerin in preventing RAS (risk ratio [RR]: 0.57 with 95% confidence interval [CI] [0.43-0.77], p = .0003) and RAO (RR: 0.39 with 95% CI [0.16-0.98], p = .05). In contrast to the intra-arterial nitroglycerin that showed nonstatistically significant results in preventing RAS and RAO (RR: 0.8 with 95% CI [0.63-1.02], p = .07)- (RR: 0.78 with 95% CI [0.6-1.01], p = .06)), respectively. Also, topical nitroglycerin did not prevent RAS (RR: 0.73 with 95% CI [0.42-1.24], p = .24). Compared with placebo, subcutaneous nitroglycerin during transradial catheterization reduced the incidence of RAS and RAO. Meanwhile, Intra-arterial and topical nitroglycerin did not show statistically significant outcomes. Subcutaneous nitroglycerin may be a practical and cost-effective technique to facilitate transradial catheterization; however, more RCTs are needed to evaluate the subcutaneous versus intra-arterial nitroglycerin administration.

Feasibility of Microbubble-Accelerated Low-Dose Thrombolysis of Peripheral Arterial Occlusions Using an Ultrasound Catheter.

Intra-arterial administration of microbubbles (MBs) through an ultrasound (US) catheter increases the local concentration of MBs into the thrombus and may further enhance outcomes of contrast-enhanced sonothrombolysis (CEST). The objective of this study was to evaluate the feasibility and lytic efficacy of intra-arterial infusion of MBs during US-enhanced thrombolysis in both in vitro and in vivo peripheral arterial occluded models. SonoVue and Luminity MBs were infused at a flow rate of 20 mL/h through either the drug delivery lumen of the US catheter (DDC, n=20) or through the tube lumen of the vascular phantom (systematic infusion, n=20) during thrombolysis with a low-dose urokinase (UK) protocol (50 000 IU/h) with(out) US application to assess MB survivability and size by pre-treatment and post-treatment measurements. A human thrombus was placed into a vascular phantom of the flow system to examine the lytic effects of CEST by post-treatment D-dimer concentrations measurements of 5 treatment conditions (saline, UK, UK+US, UK+US+SonoVue, and UK+US+Luminity). Thrombolytic efficacy of localized MBs and US delivery was then investigated in vivo in 5 porcine models by arterial blood flow, microcirculation, and postmortem determined thrombus weight and remaining length. US exposure significantly decreased SonoVue (p=0.000) and Luminity (p=0.000) survivability by 37% and 62%, respectively. In vitro CEST treatment resulted in higher median D-dimer concentrations for the SonoVue (0.94 [0.07-7.59] mg/mL, p=0.025) and Luminity (0.83 [0.09-2.53] mg/mL, p=0.048) subgroups when compared with thrombolysis alone (0.36 [0.02-1.00] mg/mL). The lytic efficacy of CEST examined in the porcine model showed an improved median arterial blood flow of 21% (7%-79%), and a median thrombus weight and length of 1.02 (0.96-1.43) g and 2.25 (1.5-4.0) cm, respectively. One allergic reaction and 2 arrhythmias were observed due to the known allergic reaction on lipids in the porcine model. SonoVue and Luminity can be combined with an US catheter and could potentially accelerate thrombolytic treatment of peripheral arterial occlusions. Catheter-directed thrombolysis showed to be an effective alternative to surgery for acute peripheral arterial occlusions, but this technique is still associated with several limb and life-threatening complications. The effects of thrombolysis on clot dissolution may be further enhanced by intra-arterial administration of microbubbles through an ultrasound catheter. This study demonstrates the feasibility and lytic efficacy of intra-arterial infusion of microbubbles during US-enhanced thrombolysis in both in vitro and in vivo peripheral arterial occluded models.

Radiation dose aspects and establishment of diagnostic reference levels for 90Y radioembolisation during angiographic procedure

90Y radioembolisation (RE) is an angiographic procedure used in patients with both primary and secondary hepatic malignancies. Local tumour control can be achieved by short range tumour irradiation by the regional intra-arterial administration of glass or resin microspheres loaded with 90yttrium that accumulate in the tumorous tissue. The aim of this study was to investigate the radiation exposure of RE and to establish a local diagnostic reference level (DRL). In this retrospective study, dose data from 397 procedures in 306 patients (mean age 67.4 ± 10.6 years, 82 female) who underwent RE between 06/2017 and 01/2022 using one of two different angiography systems were analysed. DRL was set as the 75th percentile of the dose distribution. In the overall population, dose area product (DAP) (median (interquartile range, IQR)) was 26 Gy cm2 (IQR 12–50) with a median fluoroscopy time (FT) of 4.5 min (IQR 2.9–8.0). FT and DAP increased significantly with the number of infusion positions (median, IQR): one position 23 Gy cm2 (12–46), two positions 33 Gy cm2 (14–60), three positions 50 Gy cm2 (24–82) (p < 0.0001). Local DRL is 47 Gy cm2 for RE and 111 Gy cm2 for RE with additional embolisation. Radiation exposure and FT are significantly higher with increasing number of infusion positions as well as additional embolisation. Our established DRLs for RE may serve as a benchmark for dose optimisation.