A Safe and Reliable Technique for CNS Delivery of AAV Vectors in the Cisterna Magna.

Global gene delivery to the CNS has therapeutic importance for the treatment of neurological disorders that affect the entire CNS. Due to direct contact with the CNS, cerebrospinal fluid (CSF) is an attractive route for CNS gene delivery. A safe and effective route to achieve global gene distribution in the CNS is needed, and administration of genes through the cisterna magna (CM) via a suboccipital puncture results in broad distribution in the brain and spinal cord. However, translation of this technique to clinical practice is challenging due to the risk of serious and potentially fatal complications in patients. Herein, we report development of a gene therapy delivery method to the CM through adaptation of an intravascular microcatheter, which can be safely navigated intrathecally under fluoroscopic guidance. We examined the safety, reproducibility, and distribution/transduction of this method in sheep using a self-complementary adeno-associated virus 9 (scAAV9)-GFP vector. This technique was used to treat two Tay-Sachs disease patients (30 months old and 7 months old) with AAV gene therapy. No adverse effects were observed during infusion or post-treatment. This delivery technique is a safe and minimally invasive alternative to direct infusion into the CM, achieving broad distribution of AAV gene transfer to the CNS.

Safety, efficacy, and short-term follow-up of the use of Pipeline Embolization Device in small (<2.5 mm) cerebral vessels for aneurysm treatment: single institution experience.

INTRODUCTION: Flow diversion is being increasingly used to treat cerebral aneurysms. We present our experience using these stents to treat aneurysms distal to the circle of Willis with parent arteries smaller than 2.5 mm. METHODS: Aneurysms treated with a Pipeline Embolization Device in vessels less than 2.5 mm between June 2012 and August 2014 were included. We evaluated risk factors, family history of aneurysms, aneurysm characteristics, National Institute of Health Stroke Scale (NIHSS), and modified Rankin scale (mRS) on admission and angiography and clinical outcome at discharge, 6 months, and 1 year. RESULTS: We included seven patients with a mean age of 65 years. The parent vessel size ranged from 1.5 to 2.3 mm; mean 1.9 mm. Location of the aneurysms was as follows: two aneurysms centered along the pericallosal artery (one left, one right), one on the right angular artery, one aneurysm at the anterior communicating artery (ACom), one at the ACom-right A2 anterior cerebral artery (ACA), one at the lenticulostriate artery, and one at the A1-A2 ACA artery. Aneurysms ranged from 1 to 12 mm in diameter. All aneurysms were treated with a single Pipeline Embolization Device (PED). No peri- or post-procedural complications or mortality occurred. The patients were discharged with no change in NIHSS or mRS score. Angiographic follow-up was available in six patients. Angiography showed complete aneurysm occlusion in all. NIHSS and mRS remained unchanged at follow-up. CONCLUSION: Our preliminary results show that flow diversion technology is an effective and safe therapy for aneurysms located on small cerebral arteries. Larger studies with long-term follow-up are needed to validate our promising results.

Imaging Inflammation in Cerebrovascular Disease.

Imaging inflammation in large intracranial artery pathology may play an important role in the diagnosis of and risk stratification for a variety of cerebrovascular diseases. Looking beyond the lumen has already generated widespread excitement in the stroke community, and the potential to unveil molecular processes in the vessel wall is a natural evolution to develop a more comprehensive understanding of the pathogenesis of diseases, such as ICAD and brain aneurysms.

Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular Bypass to Treat Large Vessel Occlusion.

BACKGROUND AND PURPOSE: The goal of this study is to combine temporary endovascular bypass (TEB) with a novel shear-activated nanotherapeutic (SA-NT) that releases recombinant tissue-type plasminogen activator (r-tPA) when exposed to high levels of hemodynamic stress and to determine if this approach can be used to concentrate r-tPA at occlusion sites based on high shear stresses created by stent placement. METHODS: A rabbit model of carotid vessel occlusion was used to test the hypothesis that SA-NT treatment coupled with TEB provides high recanalization rates while reducing vascular injury. We evaluated angiographic recanalization with TEB alone, intra-arterial delivery of soluble r-tPA alone, or TEB combined with 2 doses of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy. RESULTS: Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared with controls (P=0.0011). SA-NT (20 mg) had a higher likelihood of obtaining complete recanalization as compared with TEB alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), intra-arterial r-tPA alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), or TEB with soluble r-tPA (2 mg; odds ratio 18.78, 95% confidence interval 1.28, 275.05; P=0.0322). Histological analysis showed circumferential loss of endothelium restricted to the area where the TEB was deployed; however, there was significantly less vascular injury using a TEB as compared with stent-retriever procedure (odds ratio 12.97, 95% confidence interval 8.01, 21.02; P<0.0001). CONCLUSIONS: A novel intra-arterial, nanoparticle-based thrombolytic therapy combined with TEB achieves high rates of complete recanalization. Moreover, this approach reduces vascular trauma as compared with stent-retriever thrombectomy.

[Interventional neuroradiology: current options]. / Az intervenciós neuroradiológia korszeru lehetoségei.

Modern interventional neuroradiology has a leading role in the treatment of ischemic and hemorrhagic stroke, and it provides more and more important treatment options for degenerative diseases of the vertebral column and the management of correlated pain. During the last decades interventional neuroradiology has played a primary role in the treatment of intracranial berry aneurysms due to the continuous technical improvements. Ongoing studies proved superiority of mechanical stent-thrombectomy in acute proximal occlusion of cerebral arteries. Less invasive neurointerventional methods, such as vertebroplasty, are widely used in osteoporotic and neoplastic pathologic fractures of the vertebral bodies. These treatments should be performed in a specialized center by well trained physicians.

CHRONIC CEREBROSPINAL VENOUS INSUFFICIENCY--DISEASE OR MISDIAGNOSIS?

BACKGROUND AND PURPOSE: Former studies reported internal jugular vein stenosis in patients with multiple sclerosis. We aimed to evaluate if these venous stenoses were real and cerebral venous outflow of patients with multiple sclerosis differed from that of normal controls. METHODS: 20 controls were prospectively investigated by angiography and duplex ultrasound. Seven patients with multiple sclerosis underwent angiography at other centers; we reviewed these registrations and performed venous ultrasound examinations. RESULTS: Angiography displayed > 50% stenosis of internal jugular vein in 19 controls (69 ± 17% on the right and 73 ± 13% on the left side) and < 50% stenosis in 1 control (43.5% and 44.6%). All 7 patients had at least one-sided stenosis. The mean degree of stenosis was 63 ± 16% on the right and 67 ± 13% on the left side. There was no significant difference in the degree of stenosis between patients and controls. However, these "stenoses" disappeared if the contrast agent was injected at a catheter position below the orifice of the subclavian vein during venography. The venous flow volume was also similar between groups: 479.7 ± 214.1 and 509.8 ± 212.0 ml/min (right and left side) in the patients and 461.3 ± 224.3 and 513.6 ± 352.2 ml/min in the control group; p = 0.85 and 0.98 (right and left). Color and power duplex imaging also revealed normal blood flow of the internal jugular vein in all patients and controls. CONCLUSION: The cerebral venous status of patients with multiple sclerosis and controls were similar. The angiographic "stenoses" were virtual, caused by the contrast dilution effect of the non-contrast blood stream of the subclavian vein.

Pipeline for uncoilable or failed aneurysms: results from a multicenter clinical trial.

PURPOSE: To evaluate the safety and effectiveness of the Pipeline Embolization Device (PED; ev3/Covidien, Irvine, Calif) in the treatment of complex intracranial aneurysms. MATERIALS AND METHODS: The Pipeline for Uncoilable or Failed Aneurysms is a multicenter, prospective, interventional, single-arm trial of PED for the treatment of uncoilable or failed aneurysms of the internal carotid artery. Institutional review board approval of the HIPAA-compliant study protocol was obtained from each center. After providing informed consent, 108 patients with recently unruptured large and giant wide-necked aneurysms were enrolled in the study. The primary effectiveness endpoint was angiographic evaluation that demonstrated complete aneurysm occlusion and absence of major stenosis at 180 days. The primary safety endpoint was occurrence of major ipsilateral stroke or neurologic death at 180 days. RESULTS: PED placement was technically successful in 107 of 108 patients (99.1%). Mean aneurysm size was 18.2 mm; 22 aneurysms (20.4%) were giant (>25 mm). Of the 106 aneurysms, 78 met the study's primary effectiveness endpoint (73.6%; 95% posterior probability interval: 64.4%-81.0%). Six of the 107 patients in the safety cohort experienced a major ipsilateral stroke or neurologic death (5.6%; 95% posterior probability interval: 2.6%-11.7%). CONCLUSION: PED offers a reasonably safe and effective treatment of large or giant intracranial internal carotid artery aneurysms, demonstrated by high rates of complete aneurysm occlusion and low rates of adverse neurologic events; even in aneurysms failing previous alternative treatments.

Treatment of large and giant posterior communicating artery aneurysms with the Surpass streamline flow diverter: results from the SCENT trial.

BACKGROUND: The Surpass flow diverter was developed to treat intracranial aneurysms not amenable to standard treatment. Indications for use allow placement in the internal carotid artery to the terminus, including the communicating artery segment. METHODS: The Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide Neck Aneurysms (SCENT) trial is an international, multicenter, prospective, non-randomized trial comparing the outcomes of Surpass flow diverter treatment with historic control designed to evaluate the effectiveness and safety of Surpass for the treatment of wide neck (≥4 mm) large or giant intracranial aneurysms ≥10 mm. The primary effectiveness endpoint is the percentage of subjects with 100% aneurysm occlusion without significant stenosis of the parent artery and without retreatment of the target aneurysm at 12 months. The primary safety endpoint is the percentage of subjects experiencing neurologic death or major ipsilateral stroke at 12 months. We report the effectiveness and safety of flow diversion in the subgroup of posterior communicating artery (PComA) aneurysms. RESULTS: Of the 180 patients treated, 38 harbored a PComA aneurysm. Mean aneurysm size was 12.2 mm and mean neck width was 4.8 mm. The mean number of Surpass devices used was 1.1 per procedure, with 94.7% of aneurysms treated with one flow diverter. The 12 month primary effectiveness rate was 73.7% (28/38). At 36 months, 68.4% (26/38) of aneurysms remained completely occluded. The 12 month major ipsilateral stroke or neurological death rate was 10.5%. No patients with PComA occlusion after flow diverter placement (54.5%) had clinical sequelae. CONCLUSIONS: SCENT demonstrated acceptable 12 month effectiveness of flow diversion in PComA aneurysms. Despite associated PComA occlusions in many cases, arterial occlusions were clinically silent. TRIAL REGISTRATION NUMBER: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT01716117.

Rare angioproliferative tumors mimicking aggressive spinal hemangioma with epidural expansion.

BACKGROUND AND PURPOSE: We present two cases of angio-proliferative tumors that were misdiagnosed and treated as typical hemangiomas with epidural expansion. MATERIALS AND METHODS: Two middle-aged women presented with symptoms and radiological signs characteristic for aggressive hemangioma with epidural expansion. In the first case preoperative embolization and decompressive surgery with open transpedicular vertebroplasty was performed. Within less than a year, epidural recurrence of the tumor prompted for radical excision and corpectomy. The diagnosis after the histological studies and the further clinical evolution was metastasizing leiomyomatosis. No further recurrence occured during the next 6 years. In the second case percutaneous vertebroplasty was performed and complicated by epidural polymethyl-methacrylcate (PMMA) leakage, requiring urgent decompressive surgery. Histological study of the lesion raised the possibility of myopericytoma. This was confirmed 16 months later when complete vertebrectomy was performed due to severe epidural propagation of the recurring tumor. No further recurrence occurred in next the two years. CONCLUSIONS: Rare angio-proliferative tumors, like benign metastasizing leiomyoma and myopericytoma radiologically may resemble aggressive vertebral hemangiomas of the spine. Unlike hemangiomas, such tumors require radical removal due to their likely recurrence. As imaging studies may not be able to completely exclude such pathologies, bone biopsy and thorough histopathological studies are warranted prior to the therapeutic decision.

Suppression of mutant C9orf72 expression by a potent mixed backbone antisense oligonucleotide.

Expansions of a G4C2 repeat in the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating adult-onset neurodegenerative disorders. Using C9-ALS/FTD patient-derived cells and C9ORF72 BAC transgenic mice, we generated and optimized antisense oligonucleotides (ASOs) that selectively blunt expression of G4C2 repeat-containing transcripts and effectively suppress tissue levels of poly(GP) dipeptides. ASOs with reduced phosphorothioate content showed improved tolerability without sacrificing efficacy. In a single patient harboring mutant C9ORF72 with the G4C2 repeat expansion, repeated dosing by intrathecal delivery of the optimal ASO was well tolerated, leading to significant reductions in levels of cerebrospinal fluid poly(GP). This report provides insight into the effect of nucleic acid chemistry on toxicity and, to our knowledge, for the first time demonstrates the feasibility of clinical suppression of the C9ORF72 gene. Additional clinical trials will be required to demonstrate safety and efficacy of this therapy in patients with C9ORF72 gene mutations.

[Initial clinical experience with radiofrequency-guided percutaneous vertebral augmentation in the treatment of vertebral compression fractures]. / Rádiófrekvencia-támogatott percutan csigolyastabilizációval szerzett elso klinikai tapasztalataink kompressziós csigolyatörések kezelésében.

PURPOSE: Percutaenous Vertebroplasty (PVP) is effective in alleviating pain and facilitating early mobilization following vertebral compression fractures. The relatively high risk of extravertebral leakage due to uncontrolled delivery of low viscosity bone cement is an inherent limitation of the technique. The aim of this research is to investigate the ability of controlled cement delivery in decreasing the rate of such complications by applying radiofrequency heating to regulate cement viscosity. METHOD AND MATERIAL: Thirty two vetebrae were treated in 28 patients as part of an Ethics Committee approved multicenter clinical trial using RadioFreqency assisted Percutaenous Vertebral Augmentation (RF-PVA) technique. This technique is injecting low viscosity polymethylmethacrylate (PMMA) bone cement using a pressure controlled hydraulic pump and applying radiofrequency heating to increase cement viscosity prior to entering the vertebral body. All patients were screened for any cement leakage by X-ray and CT scan. The intensity of pain was recorded on a Visual Analog Scale (VAS) and the level of physical activity on the Oswestry Disability Index (ODI) prior to, one day, one month and three months following procedure. RESULTS: All procedures were technically successful. There were no clinical complication, intraspinal or intraforaminal cement leakage. In nine cases (29%) a small amount of PMMA entered the intervertebral space through the broken end plate. Intensity of pain by VAS was reduced from a mean of 7.0 to 2.5 and physical inactivity dropped on the ODI from 52% to 23% three months following treatment. CONCLUSION: In this small series controlled cement injection using RF-PVA was capable of preventing clinically hazardous extravertebral cement leakage while achieving outcomes similar to that of conventional vertebroplasty.

International teleproctoring in neurointerventional surgery and its potential impact on clinical trials in the era of COVID-19: legal and technical considerations.

BACKGROUND: Existing travel restrictions limit the mobility of proctors, significantly delaying clinical trials and the introduction of new neurointerventional devices. We aim to describe in detail technical and legal considerations regarding international teleproctoring, a tool that could waive the need for in-person supervision during procedures. METHODS: International teleproctoring was chosen to provide remote supervision during the first three intracranial aneurysm treatments with a new flow diverter (currently subject of a clinical trial) in the US. Real-time, high-resolution transmission software streamed audiovisual data to a proctor located in Canada. The software allowed the transmission of images in a de-identified, HIPAA-compliant manner. RESULTS: All three flow diverters were implanted as desired by operator and proctor and without complication. The proctor could swap between images from multiple sources and reported complete spatial and situational awareness, without any significant lag or delay in communication. Procedural times and radiologic dose were similar to those of uncomplicated, routine flow diversion cases at our institution. CONCLUSIONS: International teleproctoring was successfully implemented in our clinical practice. Its first use provided important insights for establishing this tool in our field. With no clear horizon for lifting the current travel restrictions, teleproctoring has the potential to remove the need for proctor presence in the angiography suite, thereby allowing the field to advance through the continuation of trials and the introduction of new devices in clinical practice. In order for this tool to be used safely and effectively, highly reliable connection and high-resolution equipment is necessary, and multiple legal nuances have to be considered.

Multimodal Bone Metastasis-associated Epidermal Growth Factor Receptor Imaging in an Orthotopic Rat Model.

Purpose To develop multimodality imaging techniques for measuring epidermal growth factor receptor (EGFR) as a therapy-relevant and metastasis-associated molecular marker in triple-negative mammary adenocarcinoma metastases. Materials and Methods An orthotopic bone metastasis EGFR-positive, triple-negative breast cancer (TNBC) model in rats was used for bioluminescence imaging, SPECT/CT, PET/CT, and MRI with quantitative analysis of transcripts (n = 22 rats). Receptor-specific MRI of EGFR expression in vivo was performed by acquiring spin-echo T1-weighted images after sequential administration of a pair of anti-EGFR antigen binding fragments, F(ab')2, conjugated to either horseradish peroxidase or glucose oxidase, which have complementing activities, as well as paramagnetic (gadolinium[III]-mono-5-hydroxytryptamide of 2,2',2''-(10-(2,6-dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid, or Gd-5HT-DOTAGA) or positron-emitting (gallium 68-5HT-DOTAGA) substrates for MRI and PET/CT imaging, respectively. EGFR expression was confirmed by quantitative reverse transcriptase polymerase chain reaction and immunohistochemical analyses to compare with image findings. Results After surgical intraarterial delivery of TNBC cells, rats developed tumors that diverged into either rapidly growing osteolytic or slow-growing nonosteolytic tumors. Both tumor types showed receptor-specific initial MRI signal enhancement (contrast-to-noise ratio) that was three to six times higher than that of normal bone marrow (29.4 vs 4.9; P < .01). Micro PET/CT imaging of EGFR expression demonstrated a high level of heterogeneity with regional uptake of the tracer, which corresponded to region-of-interest MRI signal intensity elevation (121.1 vs 93.3; P < .001). Analysis of metastases with corroboration of imaging results showed high levels of EGFR protein and messenger RNA, or mRNA, expression in the invasive tumor. Conclusion Convergence of multimodal molecular receptor imaging enabled comprehensive assessment of EGFR overexpression in an orthotopic model of TNBC metastasis. Keywords: Animal Studies, Molecular Imaging-Cancer, MR-Contrast Agent, Radionuclide Studies, Skeletal-Appendicular, Metastases Supplemental material is available for this article. © RSNA, 2021.

Quantitative Characterization of Recanalization and Distal Emboli with a Novel Thrombectomy Device.

PURPOSE: The first-pass effect during mechanical thrombectomy improves clinical outcomes regardless of first-line treatment approach, but current success rates for complete clot capture with one attempt are still less than 40%. We hypothesize that the ThrombX retriever (ThrombX Medical Inc.) can better engage challenging clot models during retrieval throughout tortuous vasculature in comparison with a standard stent retriever without increasing distal emboli. MATERIALS AND METHODS: Thrombectomy testing with the new retriever as compared to the Solitaire stent retriever was simulated in a vascular replica with hard and soft clot analogs to create a challenging occlusive burden. Parameters included analysis of distal emboli generated per clot type, along with the degree of recanalization (complete, partial or none) by retrieval device verified by angiography. RESULTS: The ThrombX device exhibited significantly higher rates of first-pass efficacy (90%) during hard clot retrieval in comparison with the control device (20%) (p < 0.009), while use of both techniques during soft clot retrieval resulted in equivalent recanalization. The soft clot model generated higher numbers of large emboli (>200 µm) across both device groups (p = 0.0147), and no significant differences in numbers of distal emboli were noted between the ThrombX and Solitaire techniques. CONCLUSIONS: Irrespective of clot composition, use of the ThrombX retriever demonstrated high rates of complete recanalization at first pass in comparison with a state-of-the-art stent retriever and proved to be superior in the hard clot model. Preliminary data suggest that risk of distal embolization associated with the ThrombX system is comparable to that of the control device.

Continuous thrombolysis and repeated thrombectomy with the Penumbra System in a child with hemorrhagic sinus thrombosis: technical note.

UNLABELLED: Cerebral venous sinus thrombosis (CVST) is an uncommon but potentially lethal event. When showing a malignant clinical course despite anticoagulant therapy, new endovascular techniques and technology allow the possibility of more aggressive thrombolysis and thrombectomy. The authors present a case of recanalization of an extensive cerebral thrombosis using a new endovascular thromboaspiration device, the Penumbra System. BACKGROUND AND PURPOSE: CVST in children is a rare but potentially lethal disorder. When showing a malignant progression despite anticoagulant therapy, the use of local thrombolytics and thrombectomy procedures might provide therapeutic solution. METHODS: A 16-year-old girl presented with signs and symptoms of a hemorrhagic cerebral sinus thrombosis and showed progression despite full dose anticoagulant therapy. The evolution being attributed to increasing mass effect, decompressive surgery was performed without clinical improvement. Further brain imaging demonstrated progression of the sinus thrombosis. Repeated local thrombectomy with the Penumbra thrombectomy system and continuous, relatively low dose local thrombolysis was performed during a period of 60 h, resulting in recanalization and clinical improvement. The methodology of combined thromboaspiration and thrombolysis is described. CONCLUSIONS: We present a novel method for revascularization using the Penumbra System in combination with long-term, relatively low dose thrombolysis, in the setting of both clinically and morphologically progressive, hemorrhagic sinus thrombosis. The procedure proved to be both safe and effective and may be considered in the future for patients with progressive sinovenous thrombosis despite adequate medical therapy.

Longitudinal Monitoring of Flow-Diverting Stent Tissue Coverage After Implant in a Bifurcation Model Using Neurovascular High-Frequency Optical Coherence Tomography.

BACKGROUND: Tissue growth over covered branches is a leading cause of delayed thrombotic complications after flow-diverter stenting (FDS). Due to insufficient resolution, no imaging modality is clinically available to monitor this phenomenon. OBJECTIVE: To evaluate high-frequency optical coherence tomography (HF-OCT), a novel intravascular imaging modality designed for the cerebrovascular anatomy with a resolution approaching 10 microns, to monitor tissue growth over FDS in an arterial bifurcation model. METHODS: FDS were deployed in a rabbit model (n = 6), covering the aortic bifurcation. The animals were divided in different groups, receiving dual antiplatelet therapy (DAPT) (n = 4), aspirin only (n = 1), and no treatment (n = 1). HF-OCT data were obtained in vivo at 3 different time points in each animal. For each cross-sectional image, metal and tissue coverage of the jailed ostium was quantified. Scanning electron microscopy images of harvested arteries were subsequently obtained. RESULTS: Good quality HF-OCT data sets were successfully acquired at implant and follow-up. A median value of 41 (range 21-55) cross-sectional images were analyzed per ostium for each time point. Between 0 and 30 d after implant, HF-OCT analysis showed a significantly higher ostium coverage when DAPT was not given. After 30 d, similar growth rates were found in the DAPT and in the aspirin group. At 60 d, a coverage of 90% was reached in all groups. CONCLUSION: HF-OCT enables an accurate visualization of tissue growth over time on FDS struts. The use of FDS in bifurcation locations may induce a drastic reduction of the jailed-branch ostium area.

Focal cooling of brain parenchyma in a transient large vessel occlusion model: proof-of-concept.

INTRODUCTION: The neuroprotective benefit of therapeutic hypothermia (TH) has been demonstrated, but systemic side effects and time required to achieve effective TH in acute ischemic stroke (AIS) care limits clinical use. We investigate rapid and localized cooling using a novel insulated catheter in an ischemia-reperfusion model. METHODS: In phase I (n=4), cold saline was delivered to the canine internal carotid artery via an insulated catheter. Temperature was measured using intracerebral thermocouples. The coolant flow rate was varied to meet a target temperature of 31-32°C in the hemisphere infused. In phase II (n=8), a temporary middle cerebral artery occlusion was created. Five dogs underwent localized TH at the optimal flow rate from phase I, and the remaining animals were untreated controls. Cooling was initiated 5 min before recanalization and continued for an additional 20 min following 45 min of occlusion duration. The outcome was infarct volume and neurological function. RESULTS: Ipsilateral tissue cooling rates were 2.2±2.5°C/min at a flow rate of 20-40 mL/min with an observed minimum of 23.8°C. Tissue cooling was localized to the ipsilateral side of the infusion with little impact on temperatures of the core or contralateral hemisphere of the brain. In phase II, animals tolerated TH with minimal systemic impact. Infarct volume in treated animals was 0.2±0.2 cm3, which was smaller than in sham animals (3.8±1.0 cm3) as well as six untreated historical control animals (4.0±2.8 cm3) (p=0.013). CONCLUSIONS: Proof-of-concept data show that localised brain TH can be quickly and safely achieved through a novel insulated catheter. The small infarct volumes suggest potential benefit for this approach.

A neurovascular high-frequency optical coherence tomography system enables in situ cerebrovascular volumetric microscopy.

Intravascular imaging has emerged as a valuable tool for the treatment of coronary and peripheral artery disease; however, no solution is available for safe and reliable use in the tortuous vascular anatomy of the brain. Endovascular treatment of stroke is delivered under image guidance with insufficient resolution to adequately assess underlying arterial pathology and therapeutic devices. High-resolution imaging, enabling surgeons to visualize cerebral arteries' microstructure and micron-level features of neurovascular devices, would have a profound impact in the research, diagnosis, and treatment of cerebrovascular diseases. Here, we present a neurovascular high-frequency optical coherence tomography (HF-OCT) system, including an imaging console and an endoscopic probe designed to rapidly acquire volumetric microscopy data at a resolution approaching 10 microns in tortuous cerebrovascular anatomies. Using a combination of in vitro, ex vivo, and in vivo models, the feasibility of HF-OCT for cerebrovascular imaging was demonstrated.

Vertebral artery dissection as an extremely rare cause of spinal epidural hematoma: case report and review of the literature.

OBJECTIVE: To present a patient with a cervico-thoracic ventrally located epidural hematoma caused by dissection and subsequent bleeding of the cervical portion of the vertebral artery. SUMMARY AND BACKGROUND DATA: Non traumatic epidural hematoma is a rare entity. The etiology usually is not clarified: a venous origin is usually suspected although an arterial source is also possible. CLINICAL REPORT: A 32-year-old woman presented with a ventrally located cervico-thoracic epidural hematoma caused by non traumatic dissection and dissecting aneurysm rupture of the cervical portion of the vertebral artery. The dissection was demonstrated by magnetic resonance imaging and digital subtraction angiography. The patient had no neurological symptoms and was treated by conservative methods. Follow up imaging showed healing of the vertebral artery and resorption of the epidural hematoma. CONCLUSION: Dissection of the cervical portion of the vertebral artery with subsequent perivascular bleeding is not well recognized as a possible cause of a spinal epidural hematoma. Even though this entity and the underlying cause may be rare, we suggest a vigilant search for vertebral artery injury in cases of ventrally located cervical and upper thoracic epidural hematoma.