Intra-arterial Treatment Research Articles

Endovascular surgical neuro-oncology: advancing a new subspecialty.

Endovascular surgical neuro-oncology is a relatively new subspecialty which uses endovascular neuro-interventional techniques for the management of nervous system tumors and tumor-related vascular conditions. Although there are several endovascular procedures that are widely available as standard-of-care diagnostic and treatment adjuncts, there has been a renewed interest to explore endovascular approaches as a means for selective intra-arterial delivery of therapeutic agents to nervous system tumors, including methods for opening the blood brain and blood tumor barriers. In this review, we discuss the historical development of various forms of endovascular intra-arterial treatment for tumors over the past 40 years, summarize endovascular approaches that are currently being employed, and highlight current clinical trials.

Comparison of anesthesia methods for intra-arterial therapy of patients with acute ischemic stroke: an updated meta-analysis and systematic review

ObjectivesCurrently, there remains debate regarding the optimal anesthesia approach for patients undergoing intra-arterial therapy for acute ischemic stroke. Therefore, we conducted a comparative analysis to assess the effects of general anesthesia versus non general anesthesia on patient outcomes.MethodsThe research methodology entailed comprehensive searches of prominent databases such as the Cochrane Library, PubMed, Scopus, and Web of Science, covering the period from January 1, 2010, to March 1, 2024. Data synthesis employed techniques like risk ratio or standardized mean difference, along with 95% confidence intervals. The study protocol was prospectively registered with PROSPERO (CRD42024523079).ResultsA total of 27 trials and 12,875 patients were included in this study. The findings indicated that opting for non-general anesthesia significantly decreased the risk of in-hospital mortality (RR, 1.98; 95% CI: 1.50 to 2.61; p<0.00001; I2 = 20%), as well as mortality within three months post-procedure (RR, 1.24; 95% CI: 1.15 to 1.34; p<0.00001; I2 = 26%), while also leading to a shorter hospitalization duration (SMD, 0.24; 95% CI: 0.15 to 0.33; p<0.00001; I2 = 44%).ConclusionIschemic stroke patients who undergo intra-arterial treatment without general anesthesia have a lower risk of postoperative adverse events and less short-term neurological damage. In routine and non-emergency situations, non-general anesthetic options may be more suitable for intra-arterial treatment, offering greater benefits to patients. In addition to this, the neuroprotective effects of anesthetic drugs should be considered more preoperatively and postoperatively.

Efficacy of a prolonged stability melphalan formulation for intra-arterial treatment of retinoblastoma

BackgroundMelphalan, which is poorly soluble at room temperature, is widely used for the treatment of retinoblastoma by selective ophthalmic artery infusion. Evomela, a propylene glycol-free formulation of melphalan with improved...

Early therapy evaluation of intra-arterial trastuzumab injection in a human breast cancer xenograft model using multiparametric MR imaging.

To investigate the treatment efficacy of intra-arterial (IA) trastuzumab treatment using multiparametric magnetic resonance imaging (MRI) in a human breast cancer xenograft model. Human breast cancer cells (BT474) were stereotaxically injected into the brains of nude mice to obtain a xenograft model. The mice were divided into four groups and subjected to different treatments (IA treatment [IA-T], intravenous treatment [IV-T], IA saline injection [IA-S], and the sham control group). MRI was performed before and at 7 and 14 d after treatment to assess the efficacy of the treatment. The tumor volume, apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) MRI parameters (Ktrans, Kep, Ve, and Vp) were measured. Tumor volumes in the IA-T group at 14 d after treatment were significantly lower than those in the IV-T group (13.1 mm3 [interquartile range 8.48-16.05] vs. 25.69 mm3 [IQR 20.39-30.29], p = 0.005), control group (IA-S, 33.83 mm3 [IQR 32.00-36.30], p<0.01), and sham control (39.71 mm3 [IQR 26.60-48.26], p <0.001). The ADC value in the IA-T group was higher than that in the control groups (IA-T, 7.62 [IQR 7.23-8.20] vs. IA-S, 6.77 [IQR 6.48-6.87], p = 0.044 and vs. sham control, 6.89 [IQR 4.93-7.48], p = 0.004). Ktrans was significantly decreased following the treatment compared to that in the control groups (p = 0.002 and p<0.001 for vs. IA-S and sham control, respectively). Tumor growth was decreased in the IV-T group compared to that in the sham control group (25.69 mm3 [IQR 20.39-30.29] vs. 39.71 mm3 [IQR 26.60-48.26], p = 0.27); there was no significant change in the MRI parameters. IA treatment with trastuzumab potentially affects the early response to treatment, including decreased tumor growth and decrease of Ktrans, in a preclinical brain tumor model.

Combined intravenous and intra-arterial thrombolysis in hyperacute cerebral ischemia without significant corresponding vascular occlusion/stenosis: A Preliminary investigation

ObjectiveIn this study, we assessed the efficacy and safety of various thrombolytic treatment protocols in patients with hyperacute cerebral infarction. MethodsPatients diagnosed with acute ischemic stroke within 6 h of symptom onset and with brain computer tomography angiography confirming the absence of major vessel stenosis or occlusion were eligible for this study. The enrolled patients were subsequently randomized into two groups: all the groups received the standard intravenous thrombolysis treatment with rt-PA (0.9 mg/kg), and the experimental group underwent sequential intra-arterial thrombolysis treatment with alteplase (0.3 mg/kg, with a maximum dose of 22 mg), administered directly into the target vessel via a microcatheter. Both groups were closely monitored for changes in their National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin scale score, hemorrhage rate, all-cause mortality rate, and the rate of favorable outcomes at 90 ± 7 days. ResultsNinety-four participants were enrolled in this study, with both the control and experimental groups initiating intravenous injection of rt-PA at a median time of 29 min. For the experimental group, the median time for arterial puncture was 123 min. Baseline data for both groups were similar (P > 0.05). Hemorrhagic transformation occurred in 24.47 % (23 patients), with a lower intracranial hemorrhage rate observed in the experimental group compared to the control group (15.2 % vs 33.3 %, P < 0.05). Asymptomatic hemorrhage rates were 8.7 % for the experimental group and 12.5 % for the control group, with no hemorrhage detected in other locations. Post-treatment median NIHSS scores were lower in the experimental group than in the control group (7 vs 9, P < 0.05), but short-term NIHSS scores were similar (P > 0.05). A higher proportion of patients in the experimental group achieved favorable outcomes compared to the control group (87.0 % vs 43.8 %, P < 0.05). ConclusionIn patients with acute ischemic stroke with an onset time of ≤6 h and no major intracranial vessel occlusion, combining rt-PA intravenous thrombolysis with intra-arterial thrombolysis via a microcatheter might yield superior functional outcomes.

391 Intraarterial Verapamil for Neuroprotection in Ischemic Stroke

INTRODUCTION: Verapamil is an FDA-approved calcium channel blocker administered for the standard-of-care treatment of vasospasm. Preclinical studies have shown that verapamil reduces inflammation and protects penumbra neurons from further damage and eventual death. METHODS: Patients were recruited based on inclusion and exclusion criteria in a clinical protocol reviewed and approved by two institutional review boards. The final cohort comprised 42 emergency care patients with an acute onset focal neurological deficit consistent with ischemic stroke and/or a computed tomographic scan consistent with acute cerebral ischemia. All patients were 18 years of age or older that presented within 24 hours of symptom onset and had a significant but not severe neurological deficit, measured by a National Institutes of Health Stroke Scale (NIHSS) score greater than four but less than 22. All patients received a mechanical thrombectomy intervention after identifying a large vessel occlusion (LVO). RESULTS: The Verapamil-treated group (N = 23) included 22 patients with middle cerebral artery (MCA) occlusions and 1 with a basilar posterior cerebral artery (PCA) occlusion. In these patients, investigators administered 10 mg of Verapamil intraarterially following mechanical thrombectomy. Patients exposed to control conditions (N = 19) were matched for age, biological sex, admission NIHSS score, occlusion location, administration of tPA, and achieved TICI score. Intraarterial Verapamil treatment did not significantly increase sICH, hemorrhagic transformation, or death compared to standard of care treatment, demonstrating safety in an acute ischemic stroke patient population. Verapamil treatment was associated with significantly greater changes in mRS score, improved recovery time, and shortened length of hospital stay compared to standard-of-care treatment. CONCLUSIONS: This study suggests that verapamil is a safe and effective neuroprotective drug in ischemic stroke clinical populations that require mechanical thrombectomy for treatment.

388 The First Endovascular Rat Glioma Model for Pre-clinical Evaluation of Intra-arterial Therapeutics

INTRODUCTION: Several translational animal models have been described assessing intra-arterial (IA) treatments for malignant gliomas. We describe the first endovascular animal model that allows testing of IA drug delivery as first-line treatment, which is difficult to do in actual patients. METHODS: Wistar rats underwent left femoral artery catherization with a Balt Magic 1.2F catheter or Marathon Flow directed 1.5F Microcatheter with an Asahi Chikai 0.008 micro-guidewire which was navigated to the left internal carotid artery under x-ray. 25% mannitol was administered to test blood brain barrier breakdown (BBBB). Additional rats were implanted with C6 glioma cells in the left frontal lobe. C6 Glioma-Implanted Rats were monitored for overall survival and tumor growth. Tumor volumes from MRI images were calculated utilizing 3D slicer. Additional rats underwent femoral artery catheterization with Bevacizumab, carboplatin, or irinotecan injected into the left internal carotid artery to test feasibility and safety. RESULTS: A successful endovascular access and BBBB protocol was established. BBBB was confirmed with positive Evans-blue staining. 10 rats were successfully implanted with C6 gliomas with confirmed growths on MRI. Overall survival was 19.75 ± 2.21 days. 5 rats were utilized for development of our femoral catheterization protocol and BBBB testing. With regards to IA chemotherapy dosage testing, control rats tolerated targeted 10 mg/kg of bevascizumab, 2.4 mg/kg of carboplatin, and 15 mg/kg of irinotecan IA ICA injections without complications. CONCLUSIONS: We present the first endovascular IA rat glioma model that allows selective catheterization of the intracranial vasculature and assessment of IA therapies for gliomas without need for access and sacrifice of proximal cerebrovasculature.

Recurrent Intrahepatic Cholangiocarcinoma: A 10-Point Score to Predict Post-Recurrence Survival and Guide Treatment of Recurrence.

Although up to 50-70% of patients with intrahepatic cholangiocarcinoma (ICC) recur following resection, data to predict post-recurrence survival (PRS) and guide treatment of recurrence are limited. Patients who underwent resection of ICC between 2000 and 2020 were identified from an international, multi-institutional database. Data on primary disease as well as laboratory and radiologic data on recurrent disease were collected. Factors associated with PRS were examined and a novel scoring system to predict PRS (PRS score) was developed and internallyvalidated. Among 986 individuals who underwent resection for ICC, 588 (59.6%) patients developed recurrence at a median follow up of 20.3months. Among patients who experienced a recurrence, 97 (16.5%) underwent re-resection/ablation for recurrent ICC; 88 (15.0%) and 403 (68.5%) patients received intra-arterial treatment or systemic chemotherapy/supportive therapy, respectively. Patient American Society of Anesthesiologists (ASA) class > 2 (1 point), primary tumor N1/Nx status (1 point), primary R1 resection margin (1 point), primary tumor G3/G4 grade(1 point), carbohydrate antigen (CA) 19-9 > 37 UI/mL (2 points) at recurrenceand carcinoembryonic antigen (CEA) > 5ng/mL (2 points) at recurrence, as well as recurrent bilateral disease (1 point) and early recurrence (1 point) were included in thePRS score. The PRS score successfully stratified patients relative to PRS and demonstrated strong discriminatory ability (C-index 0.70, 95% confidence interval 0.68-0.72). While a PRS score of 0-3 was associated with a 3-year PRS of 62.5% following resection/ablation for recurrent ICC, a PRS score > 3 was associated with a low 3-year PRS of 35.5% (p = 0.03). The PRS score demonstrated strong discriminatory ability to predict PRS among patients who had developed recurrencefollowing initial resection of ICC. The PRS score may be a useful tool to guide treatment among patients with recurrent ICC.

Immediate angiographic control after intra-arterial nimodipine administration underestimates the vasodilatory effect

Intra-arterial nimodipine administration is a widely used rescue therapy for cerebral vasospasm. Although it is known that its effect sets in with delay, there is little evidence in current literature. Our aim was to prove that the maximal vasodilatory effect is underestimated in direct angiographic controls. We reviewed all cases of intra-arterial nimodipine treatment for subarachnoid hemorrhage-related cerebral vasospasm between January 2021 and December 2022. Inclusion criteria were availability of digital subtraction angiography runs before and after nimodipine administration and a delayed run for the most affected vessel at the end of the procedure to decide on further escalation of therapy. We evaluated nimodipine dose, timing of administration and vessel diameters. Delayed runs were performed in 32 cases (19 patients) with a mean delay of 37.6 (± 16.6) min after nimodipine administration and a mean total nimodipine dose of 4.7 (± 1.2) mg. Vessel dilation was more pronounced in delayed vs. immediate controls, with greater changes in spastic vessel segments (n = 31: 113.5 (± 78.5%) vs. 32.2% (± 27.9%), p < 0.0001) vs. non-spastic vessel segments (n = 32: 23.1% (± 13.5%) vs. 13.3% (± 10.7%), p < 0.0001). In conclusion intra-arterially administered nimodipine seems to exert a delayed vasodilatory effect, which should be considered before escalation of therapy.

Abstract WMP111: Intra-Arterial Administration of Cerebral Endothelial Cell Derived Small Extracellular Vesicles Reduces Neurovascular Damage and Improves Neurological Outcome After Acute Ischemia in the Aged Rat

Stroke is a leading cause of death and disability worldwide, mainly affecting the elderly. Endovascular thrombectomy (EVT) is a standard of care therapy for stroke patients with large-vessel occlusion, however, the majority of these patients do not achieve full functional improvement. The present study tested the hypothesis that intra-arterial (IA) administration of cerebral endothelial cell derived small extracellular vesicles (CEC-sEVs) following transient middle cerebral artery occlusion (tMCAO) improves stroke outcome in the aged rat. CEC-sEVs (1x10 11 particles/injection) isolated from healthy adult rats were employed. Male aged rats (18 months, n=10/group) subjected to 3h tMCAO were randomly divided into the experimental groups. To examine whether IA injection of CEC-sEVs improves stroke outcome, CEC-sEVs were administered via the internal carotid artery (ICA) immediately following reperfusion by withdrawal of the occlusion filament. To examine whether intravenous administration (IV) of CEC-sEVs during tMCAO and then followed by IA CEC-sEVs upon reperfusion further enhances stroke outcome, CEC-sEVs were given at 30 min of tMCAO via a tail vein and upon reperfusion via the ICA. The ischemic rats treated with IA saline were used as a control. Neurological outcome and infarct volume were assessed in a blinded manner. IA CEC-sEVs upon reperfusion significantly reduced infarct volume (24±5% vs 31±6% in saline, p&lt;0.05) which was associated with robust improvement of neurological function from weeks 2 to 4 after tMCAO compared to saline treated rats. Moreover, rats treated with CEC-sEVs IV at 30min followed by IA treatment upon reperfusion further reduced infarct volume (16±6%) compared to rats treated with IA saline or CEC-sEVs. These rats also exhibited robust and early improvement of neurological function starting at 1d after tMCAO. In conclusion, IA administration of CEC-sEVs upon reperfusion significantly reduces ischemic damage, while an additional early (30min post stroke) dose of IV CEC-sEVs further enhances and accelerates the therapeutic effect of IA CEC-sEVs in the aged rats after tMCAO. Our data suggest that CEC-sEVs could potentially may be a therapy to amplify the efficacy of EVT even for elderly patients with acute ischemic stroke.

Abstract WP194: Quantified Effects of Intra-Arterial Vasodilatory Therapy for Cerebral Vasospasm

Introduction: Cerebral vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Though used routinely in clinical practice, objective metrics to evaluate effectiveness of intra-arterial vasodilatory treatment (IAT) have not been identified. To quantify effects of IAT on flow dynamics in cerebral vasospasm, we retrospectively compared Lindegaard ratios (LR) of aSAH patients pre-and post-IAT. Methods: Subjects included 24 aSAH patients undergoing IAT in the bilateral middle cerebral arteries (MCA) for cerebral vasospasm, diagnosed by standard clinical and radiographic criteria. Subjects were excluded if balloon angioplasty was performed prior to/within 2 days of the index procedure. All subjects received 10 mg IA milrinone, a non-catecholamine phosphodiesterase inhibitor drug, per MCA. Transcranial doppler (TCD) ultrasound was measured pre-IAT (D0) and at D+1 and D+2 post-IAT. LR was calculated as the ratio of mean flow velocities in the middle cerebral artery (MCA) to the ipsilateral extracranial internal carotid artery. Standard threshold for vasospasm is defined as LR&gt;3. Results: Right and left LR were aggregated, total N=48. Average pre-IAT LR was 2.96 (R 2.67/L 3.25±1.29). Post-IA LR were 2.72±1.12 and 3.15±1.55 at D+1 and D+2, respectively. Subjects with pre-IA LR&gt;3 showed an average LR decrease of 21% post-IAT D+1 (p=0.01) and an 8% decrease at D+2 (p=0.16) [Fig.1A]. Subjects with pre-IAT&lt;3 experienced an average LR increase of 28% by D+2 (p=0.02) [Fig 1B]. Conclusion: Subjects with TCD confirmed vasospasm (LR&gt;3) at D0 showed a significant improvement in cerebral blood flow one day after therapy. Subjects who did not meet TCD threshold for vasospasm (LR&lt;3) showed little change one day post-IAT but worsening cerebral blood flow by day two post-IAT. Further study is needed to determine whether LR can be used to predict benefit or objectively assess effectiveness of IAT in aSAH patients with cerebral vasospasm.

Practical Considerations When Choosing Chemoembolization versus Radioembolization for Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are common liver-directed therapies (LDTs) for unresectable HCC. While both deliver intra-arterial treatment directly to the site of the tumor, they differ in mechanisms of action and side effects. Several studies have compared their side effect profile, time to progression, and overall survival data, but often these lack practical considerations when choosing which treatment modality to use. Many factors can impact operator's choice for treatment, and the choice depends on treatment availability, cost, insurance coverage, operator's comfort level, patient-specific factors, tumor location, tumor biology, and disease stage. This review discusses survival data, time to progression data, as well as more practical patient and tumor characteristics for personalized LDT with TACE or TARE.

Continuous direct intraarterial treatment of meningitis-induced vasospasm in a pediatric patient: illustrative case.

Bacterial meningitis-induced ischemic stroke continues to cause significant long-term complications in pediatric patients. The authors present a case of severe right internal carotid artery terminus and M1 segment vasospasm in a 9-year-old with an infected cholesteatoma, which was refractory to multiple intraarterial treatments with verapamil and milrinone. This is the first report of continuous intraarterial antispasmodic treatment in a pediatric patient as well as the first report of continuous treatment in an awake and extubated patient. Arterial narrowing was successfully treated by continuous direct intraarterial administration of both a calcium channel blocker (verapamil) and a phosphodiesterase-3 inhibitor (milrinone). The patient recovered remarkably well and was discharged home with no neurological deficit (National Institutes of Health Stroke Scale score 0) and ambulatory without assistance after 22 days. The authors report a promising outcome of this technique performed in a pediatric patient. This represents a novel treatment option for the prevention of stroke in pediatric bacterial meningitis. Continuous, direct intraarterial administration of antispasmodic medications can successfully prevent long-term neurological deficit in pediatric meningitis-associated vasospasm. The described method has the potential to significantly improve outcomes in severe pediatric meningitis-associated vasospasm.

French Interventional Radiology Centers' Uptake of Transradial Approach and Outpatient Hepatocellular Carcinoma Intra-Arterial Treatments.

This study aims to investigate the uptake of transradial approach (TRA) and outpatient setting for transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) in the treatment of hepatocellular carcinoma (HCC) among French interventional radiology centers. This cross-sectional study was based on a 34-question survey assessing center activity, radial access, and outpatient care. The survey was developed by a working group, tested by two external experts, and distributed to active members of two French radiological societies via a web-based self-reporting questionnaire in March 2022. The survey remained open for eight weeks, with two reminder emails sent to non-responders. Only one answer per center was considered. Of the 44 responding centers, 39% (17/44) performed TRA for TACE and/or TARE, with post-procedure patient comfort as main motivation. Among the 27 centers not performing TRA, 33% (9/27) reported a lack of technical experience, but all 27 intended to adopt TRA within two years. Only six centers performed TACE or TARE in an outpatient setting. Reasons limiting its implementation included TACE for HCC not being a suitable intervention (61%, 27/44) and organizational barriers (41%, 18/44). Among centers not performing outpatient TACE or TARE, 34% (13/38) said "No," 34% (13/38) said "Maybe," and 32% (12/38) said "Yes" when asked about adopting it within two years. French interventional radiologists have low TRA uptake for HCC treatment, but TRA adoption potential exists. Respondents were uncertain about performing TACE or TARE in an outpatient setting within a 2-year horizon.

A personalized Monte Carlo study of tumor and critical organ doses for Trans-arterial Radioembolization patients.

Trans-arterial Radioembolization (TARE) is an intra-arterial treatment method for liver malignancies. In this procedure, the therapeutic tumor dose is significant for predicting the treatment effectiveness while the dose absorbed in an organ at risk provides an understanding of its tolerance to radiation. This study proposes a Monte Carlo (MC) approach for determining absorbed organ doses for patients undergoing TARE treatment. The technique is based on the use of a voxel-based partial body model generated for each patient from his/her anatomical image data to represent the critical body structures more realistically. These structures are first segmented from image slices to create an image block which is then incorporated into a radiation transport package (MCNP6.2) to perform MC simulations. When used along with the parameters specific to a patient's treatment, such as lung-shunt factor (LSF), tumor-to-normal liver ratio (TLR), fractional uptakes, and administered activity, this approach allowed more accurate simulation of radiation interactions and hence provided absorbed doses specific to a TARE patient. The MC method also calculated the absorbed doses in organs or tissues that were close to target tissues for which the MIRD formalism makes no predictions. MIRD calculations were found to overestimate the absorbed doses by as much as 11% in lungs, 5% in liver, and 20% in tumor volumes. This raises concerns about the treatment's efficacy when estimating the correct activity to be administered to a patient. When each patient simulation was repeated with a 90Y source spectrum to reflect the distribution of varying beta energies, the liver and the lungs were observed to receive relatively lower doses than those obtained with monoenergetic beta particles. Thus, it can be stated that the approach adopted in this study offers a more precise model of the patient's critical tissues and serves as a personalized dosimetric tool for TARE treatment planning.

Intra-arterial lidocaine therapy via the middle meningeal artery for migraine headache: Theory, current practice and future directions.

Recent developments in neurointerventional research have seen the emergence of the middle meningeal artery (MMA) as an effective conduit for intra-arterial (IA) therapy for a number of pathologies. Here, we review the anatomical, pathophysiological and experimental basis for utilisation of the MMA for IA treatment of migraine headache. We explore the in-human case literature for the treatment of headaches with IA lidocaine and discuss considerations and challenges for future research.

TIPS-17 A FIRST-IN-HUMAN FEASIBILITY STUDY TO EVALUATE THE SAFETY OF SELECTIVE INTRA-ARTERIAL YTTRIUM-90 MICROSPHERE TREATMENT IN PATIENTS WITH RECURRENT GLIOBLASTOMA (THE FRONTIER TRIAL)

Abstract BACKGROUND: Glioblastoma (GBM) is the most aggressive primary brain tumor that virtually always recurs with no established standard therapy at recurrence. Median survival after recurrence is 7-12 months. Selective internal radiation therapy (SIRT) with Yttrium-90 (Y90) glass microspheres (TheraSphere™, Boston Scientific, Marlborough, MA) is an FDA approved standard treatment for hepatocellular carcinoma, and represents a novel strategy to treat regionally localized brain tumors. We are conducting a first-in-human clinical trial (under IDE) using Y90 microspheres modified to treat tumors in the brain. The goal of selectively delivering Y90 intra-arterially is to achieve higher tumoral absorbed doses while limiting non-target exposure. DESIGN: The primary objective is to evaluate the safety of Y90 microspheres treatment. Target enrollment is 12 patients at 5 participating medical centers. Key inclusion criteria include: 1st or 2nd recurrence of GBM , size 1-5cm, located in the non-dominant hemisphere in a non-eloquent region, accessible neurovascular anatomy for single intra-arterial treatment based on a diagnostic cerebral angiogram. After consent, patients will undergo screening angiography and imaging that be reviewed by the trial steering committee to determine treatment suitability. Treatment consists of Y90 microspheres administered intra-arterially to deliver 40Gy ± 10% to the treatment volume. Post-administration Y90 PET and MRI images allow assessment of dose distribution and acute safety. Following overnight admission, patients will be followed as outpatients weekly x 4, and then monthly up to month 6. Primary endpoints include treatment-related limiting toxicities, dose limiting toxicity defined as non-hematological toxicities ≥ grade 3, CNS toxicity ≥ grade 3 (eg. symptomatic ischemia or edema) related to non-target embolization, occurring through 30 days post procedure. Secondary endpoints include: treatment-related serious adverse events, change in post-treatment neurological function, technical success, objective response rate, progression-free survival, and overall survival. The study is registered with clinicaltrials.gov, number: NCT05303467.

Angiogenesis and Hepatocellular Carcinoma: From Molecular Mechanisms to Systemic Therapies.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The hypervascular nature of the majority of HCCs and the peculiar vascular derangement occurring during liver carcinogenesis underscore the importance of angiogenesis in the development and progression of these tumors. Indeed, several angiogenic molecular pathways have been identified as deregulated in HCC. The hypervascular nature and the peculiar vascularization of HCC, as well as deregulated angiogenic pathways, represent major therapeutic targets. To a large extent, intra-arterial locoregional treatments (transarterial-(chemo)embolization) rely on tumor ischemia caused by embolization of tumor feeding arteries, even though this may represent the "primum movens" of tumor recurrence through the activation of neoangiogenesis. Considering systemic therapies, the currently available tyrosine kinase inhibitors (sorafenib, regorafenib, cabozantinib and lenvatinib) and monoclonal antibodies (ramucirumab and bevacizumab, in combination with the anti-PD-L1, atezolizumab) primarily target, among others, angiogenic pathways. Considering the importance of angiogenesis in the pathogenesis and treatment of liver cancer, in this paper, we aim to review the role of angiogenesis in HCC, addressing the molecular mechanisms, available antiangiogenic therapies and prognostic biomarkers in patients receiving these treatments.

The first endovascular rat glioma model for pre-clinical evaluation of intra-arterial therapeutics.

Several translational animal models have been described assessing intra-arterial (IA) treatments for malignant gliomas. We describe the first endovascular animal model that allows testing of IA drug delivery as a first-line treatment, which is difficult to do in actual patients. We report a unique protocol for vascular access and IA delivery in the rat model that, unlike prior reports, does not require direct puncture and opening of proximal cerebrovasculature which carries risk of ischemia in the animal brain post-delivery. Wistar rats underwent left femoral artery catherization with a Balt Magic 1.2F catheter or Marathon Flow directed 1.5F Microcatheter with an Asahi Chikai 0.008 micro-guidewire which was navigated to the left internal carotid artery under x-ray. 25% mannitol was administered to test blood brain barrier breakdown (BBBB). Additional rats were implanted with C6 glioma cells in the left frontal lobe. C6 Glioma-Implanted Rats (C6GRs) were monitored for overall survival and tumor growth. Tumor volumes from MRI images were calculated utilizing 3D slicer. Additional rats underwent femoral artery catheterization with Bevacizumab, carboplatin, or irinotecan injected into the left internal carotid artery to test feasibility and safety. A successful endovascular access and BBBB protocol was established. BBBB was confirmed with positive Evans blue staining. 10 rats were successfully implanted with C6 gliomas with confirmed growths on MRI. Overall survival was 19.75 ± 2.21 days. 5 rats were utilized for the development of our femoral catheterization protocol and BBBB testing. With regards to IA chemotherapy dosage testing, control rats tolerated targeted 10 mg/kg of bevascizumab, 2.4 mg/kg of carboplatin, and 15 mg/kg of irinotecan IA ICA injections without any complications. We present the first endovascular IA rat glioma model that allows selective catheterization of the intracranial vasculature and assessment of IA therapies for gliomas without need for access and sacrifice of proximal cerebrovasculature.

Recanalized paramedian thalamoperforators after intraarterial tirofiban treatment in a patient with bilateral fetal-type PCAs (P8-5.028)

<h3>Objective:</h3> NA <h3>Background:</h3> There are increasing evidence that support the treatment effect of intraarterial tirofiban during endovascular thrombectomy in acute ischemic stroke. Here, we report a patient with bilateral fetal-type PCAs, whose paramedian perforating thalamic-mesencephalic arteries were recanalized after intraarterial tirofiban treatment during thrombectomy. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 78-year-old woman presented to the emergency room with acute onset of drowsy mentality, gaze palsy and quadriplegia (NIHSS 9). She had a history of hypertension and diabetes. Brain CT scan revealed no definite early ischemic damage and CTA showed steno-occlusion at the left distal VA and bilateral fetal type PCAs. Brain perfusion CT showed perfusion delay in posterior circulation territory. Under local anesthesia, an 6F Envoy^® catheter (Codman) was placed in the left distal VA of distal V2 segment. The angiography revealed the distal VA occlusion (V4 segment) (Fig. 1A). Suction thrombectomy was performed twice using 5F Sofia^® catheter (Microvention), and no clot was extracted (Fig. 1B). Recanalization of left distal VA with underlying severe ICAS at the occlusion site (Fig. 1C). Delayed angiogram showed subtle re-occlusion tendency of left distal VA, 0.5mg of intraarterial tirofiban was injected. Successful recanalization (mTICI 2C) with further recanalized paramedian perforating thalamic-mesencephalic arteries on distal BA after SCA branches was achieved (Fig. 1D). Follow-up brain MRI showed acute infarction at the posterior circulation territory including bilateral thalami. MRA showed patent left distal VA with underlying severe ICAS, and vessel wall MRI showed eccentric wall thickening without contrast enhancement or plaque hemorrhage. The patient recovered well at 1 week (NIHSS 0). <h3>Conclusions:</h3> In a patient with bilateral fetal type PCAs, distal BA could end after SCA branches and this site should be evaluated cautiously, because thalamoperforators could originate. Intraarterial tirofiban could be helpful to recanalize perforating arteries during thrombectomy. <b>Disclosure:</b> Dr. Baik has nothing to disclose.