Novel Technique of Head-Mounted Augmented Reality-Assisted Endovascular Neurosurgery: Proof of Concept on a Flow Model.

Augmented reality (AR) is an emerging technology in medicine that is underexplored in the endovascular neurosurgery arena. We describe a novel technique integrating the Hololens 2 head-mounted AR (HMAR) system for navigation of the intracranial circulation and simple coiling of an aneurysm silicone model. Computed tomography angiographies (CTAs) of the silicone models were obtained, simulating the preprocedural CTA obtained for patient treatments. CTA was imported into the 3-dimensional (3D) HMAR system, and a 3D hologram of the circulation was created. Using the right common carotid artery run (performed in the silicon model) as a landmark, the AR hologram was superimposed on the angiography screen (Video 1). A 5-French sheath, intermediate catheter, 0.012-inch microcatheter, and microwire were used for the purely navigational model. The same process was repeated with the aneurysm model, which was navigated with a 0.58 intermediate catheter, 0.17 microcatheter, 0.014 microwire, and 6 × 15 3D-shaped soft coil. The proximal and distal vessels of the flow model were successfully navigated using the AR hologram, which replaced the conventional roadmap. No contrast ¨puffs¨ were needed because the hologram replaced the roadmap from proximal to distal vasculature. The silicon navigational model and aneurysm model were successfully navigated using only the AR 3D model. A coil was deployed in the aneurysm model. Finally, a 3D-360-degree examination of the aneurysmal anatomy was possible during the procedure. The concept of HMAR-assisted cerebral angiography is feasible. We were able to perform the whole intracranial navigation using only the preoperative CTA. Additional refinements and fine-tuning of the registration and alignment of the hologram to the silicon model or anatomy of the patient are needed before this technology can be incorporated into clinical practice. In the meantime, the use of this tool for the training and development of endovascular skills offers valuable educational opportunities. Further advances in this direction aiming to create real 3D roadmaps are needed to decrease contrast use, radiation exposure, and navigation times.

Vertebral-Venous fistulas: Single center experience and practical treatment approach.

BACKGROUND: Vertebral-venous fistulas (VVFs) are rare. Scarce literature exists to guide our understanding and management. We report our experience and propose a classification based on flow, feeder number, and involvement of accessible veins. Additionally, we include a practical treatment approach. METHODS: Retrospective chart and imaging review of cerebrovascular arteriovenous fistulas treated in our center between July 2013 and April 2022. We reviewed patient demographics, presentation, imaging, treatment strategies, and outcomes. RESULTS: Nine patients with VVFs were identified, six were females. Ages ranged between 38-83 years. There were six high-flow and three low-flow. Most VVFs originated at the level of V3. Additional feeders from the internal carotid artery, external carotid artery, and/or subclavian artery were present in four cases (two were high-flow). Four cases had multiple arterial feeders. All cases were symptomatic. Origin was spontaneous in eight and iatrogenic in one case. Most common presenting symptoms were pain (7) and pulsatile tinnitus (4). Neurological deficits were present in two cases (1 high- and 1 low-flow). Four cases were treated with vertebral artery segmental sacrifice alone, three required multiple transarterial embolizations with or without VA sacrifice, one case had single transvenous approach, and one was treated with single targeted transarterial embolization. One patient had a minor transient neurological complication. No treatment-related mortality was seen. CONCLUSION: Treatment of high-flow and symptomatic low-flow VVFs is feasible and safe. Our classification and treatment approach might help guide patient selection and choice of endovascular approach. However, our approach warrants further validation with a larger number of patients.

Head-Mounted Augmented Reality in the Planning of Cerebrovascular Neurosurgical Procedures: A Single-Center Initial Experience.

BACKGROUND: Augmented reality (AR) technology has played an increasing role in cerebrovascular neurosurgery over the last 2 decades. Hence, we aim to evaluate the technical and educational value of head-mounted AR in cerebrovascular procedures. METHODS: This is a single-center retrospective study of patients who underwent open surgery for cranial and spinal cerebrovascular lesions between April and August 2022. In all cases, the Medivis Surgical AR platform and HoloLens 2 were used for preoperative and intraoperative (preincision) planning. Surgical plan adjustment due to the use of head-mounted AR and subjective educational value of the tool were recorded. RESULTS: A total of 33 patients and 35 cerebrovascular neurosurgical procedures were analyzed. Procedures included 12 intracranial aneurysm clippings, 6 brain and 1 spinal arteriovenous malformation resections, 2 cranial dural arteriovenous fistula obliterations, 3 carotid endarterectomies, two extracranial-intracranial direct bypasses, two encephaloduroangiosynostosis for Moyamoya disease, 1 biopsy of the superficial temporal artery, 2 microvascular decompressions, 2 cavernoma resections, 1 combined intracranial aneurysm clipping and encephaloduroangiosynostosis for Moyamoya disease, and 1 percutaneous feeder catheterization for arteriovenous malformation embolization. Minor changes in the surgical plan were recorded in 16 of 35 procedures (45.7%). Subjective educational value was scored as "very helpful" for cranial, spinal arteriovenous malformations, and carotid endarterectomies; "helpful" for intracranial aneurysm, dural arteriovenous fistulas, direct bypass, encephaloduroangiosynostosis, and superficial temporal artery-biopsy; and "not helpful" for cavernoma resection and microvascular decompression. CONCLUSIONS: Head-mounted AR can be used in cerebrovascular neurosurgery as an adjunctive tool that might influence surgical strategy, enable 3-dimensional understanding of complex anatomy, and provide great educational value in selected cases.

Impact of Balloon Guide Catheter Use on Clinical and Angiographic Outcomes in the STRATIS Stroke Thrombectomy Registry.

Background and Purpose- Mechanical thrombectomy has been shown to improve clinical outcomes in patients with acute ischemic stroke. However, the impact of balloon guide catheter (BGC) use is not well established. Methods- STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever as first-line therapy. In this study, an independent core laboratory, blinded to the clinical outcomes, reviewed all procedures and angiographic data to classify procedural technique, target clot location, recanalization after each pass, and determine the number of stent retriever passes. The primary clinical end point was functional independence (modified Rankin Scale, 0-2) at 3 months as determined on-site, and the angiographic end point was first-pass effect (FPE) success rate from a single device attempt (modified Thrombolysis in Cerebral Infarction, ≥2c) as determined by a core laboratory. Achieving modified FPE (modified Thrombolysis in Cerebral Infarction, ≥2b) was also assessed. Comparisons of clinical outcomes were made between groups and adjusted for baseline and procedural characteristics. All participating centers received institutional review board approval from their respective institutions. Results- Adjunctive technique groups included BGC (n=445), distal access catheter (n=238), and conventional guide catheter (n=62). The BGC group had a higher rate of FPE following first pass (212/443 [48%]) versus conventional guide catheter (16/62 [26%]; P=0.001) and distal access catheter (83/235 [35%]; P=0.002). Similarly, the BGC group had a higher rate of modified FPE (294/443 [66%]) versus conventional guide catheter (26/62 [42%]; P<0.001) and distal access catheter (129/234 [55%]; P=0.003). The BGC group achieved the highest rate of functional independence (253/415 [61%]) versus conventional guide catheter (23/55 [42%]; P=0.007) and distal access catheter (113/218 [52%]; P=0.027). Final revascularization and mortality rates did not differ across the groups. Conclusions- BGC use was an independent predictor of FPE, modified FPE, and functional independence, suggesting that its routine use may improve the rates of early revascularization success and good clinical outcomes. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

Down syndrome associated moyamoya may worsen epilepsy control and can benefit from surgical revascularization.

OBJECTIVES: To examine outcome of bilateral extracranial to intracranial (EC-IC) bypass surgeries for a Down syndrome patient with hard-to-treat epilepsy and moyamoya. MATERIALS AND METHODS: Superficial temporal arteries were anastamosed using an indirect bypass technique to middle cerebral arteries bilaterally to help limit perfusion deficits and seizure controls. RESULTS: Two superficial temporal to middle cerebral artery indirect bypass surgeries were performed within 3 months. Post-revascularization improvements included seizure control, gait, perfusion, wakefulness, language and quality of life. CONCLUSION: In patients with Down syndrome and moyamoya, improvements in seizure control and quality of life may occur with EC-IC bypass procedures.

Preoperative relative cerebral blood volume analysis in gliomas predicts survival and mitigates risk of biopsy sampling error.

Appropriate management of adult gliomas requires an accurate histopathological diagnosis. However, the heterogeneity of gliomas can lead to misdiagnosis and undergrading, especially with biopsy. We evaluated the role of preoperative relative cerebral blood volume (rCBV) analysis in conjunction with histopathological analysis as a predictor of overall survival and risk of undergrading. We retrospectively identified 146 patients with newly diagnosed gliomas (WHO grade II-IV) that had undergone preoperative MRI with rCBV analysis. We compared overall survival by histopathologically determined WHO tumor grade and by rCBV using Kaplan-Meier survival curves and the Cox proportional hazards model. We also compared preoperative imaging findings and initial histopathological diagnosis in 13 patients who underwent biopsy followed by subsequent resection. Survival curves by WHO grade and rCBV tier similarly separated patients into low, intermediate, and high-risk groups with shorter survival corresponding to higher grade or rCBV tier. The hazard ratio for WHO grade III versus II was 3.91 (p = 0.018) and for grade IV versus II was 11.26 (p < 0.0001) and the hazard ratio for each increase in 1.0 rCBV units was 1.12 (p < 0.002). Additionally, 3 of 13 (23%) patients initially diagnosed by biopsy were upgraded on subsequent resection. Preoperative rCBV was elevated at least one standard deviation above the mean in the 3 upgraded patients, suggestive of undergrading, but not in the ten concordant diagnoses. In conclusion, rCBV can predict overall survival similarly to pathologically determined WHO grade in patients with gliomas. Discordant rCBV analysis and histopathology may help identify patients at higher risk for undergrading.

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (P<0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06-1.79; P=0.02). Likewise, excellent outcome (modified Rankin Score 0-1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13-1.92; P=0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P=0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640.

Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke: Primary Results of the STRATIS Registry.

BACKGROUND AND PURPOSE: Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials. METHODS: STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis. RESULTS: A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab-adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2. CONCLUSIONS: This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.

Arterial variations around the atlas: a comprehensive review for avoiding neurosurgical complications.

INTRODUCTION: Neurosurgical approaches often involve the atlas. Therefore, the arterial relationships and anatomical variations are of paramount importance to the neurosurgeon. METHODS: Using standard search engines, a literature review of arterial variants near the first cervical vertebra was performed. CONCLUSIONS: Arterial variations around the atlas are surgically significant. Awareness of their existence and course may provide better pre-operative planning and surgical intervention, potentially leading to better clinical outcomes. Three-dimensional computed tomography angiography (3D CTA) is an important tool for identifying and diagnosing such abnormalities and should be used when such vascular anomalies are suspected.

The use of adenosine in the treatment of a high-flow vein of Galen malformation in an adult.

The treatment of high-flow vein of Galen aneurysmal malformations (VGAM) remains a therapeutic challenge for the neurosurgeon and the neurointerventionalist, as it is associated with high morbidity and mortality rates despite recent advances in open cranial surgery and interventional neuroradiology. A 37-year-old patient presented with a history of non-specific headaches. He had a history of heart failure since birth that was caused by an untreated VGAM. Intravenous boluses of adenosine were injected as an attempt to slow down the arteriovenous shunting of a VGAM prior to endovascular treatment. Adenosine can be a very useful adjunct in patients with extremely high arteriovenous shunting. n-butyl cyanoacrylate (n-BCA) should be the embolic material of choice due to its quick polymerization and adhesive properties.

Endovascular treatment of fusiform cerebral aneurysms with the Pipeline Embolization Device.

OBJECT: Despite advances in surgical and endovascular techniques, fusiform aneurysms remain a therapeutic challenge. Introduction of flow-diverting stents has revolutionized the treatment of aneurysms with wide necks and of complex morphology. The authors report their experience with the endovascular treatment of fusiform aneurysms using the Pipeline Embolization Device. METHODS: A retrospective review of 146 patients with cerebral aneurysms treated with the Pipeline Embolization Device between June 2011 and January 2013 was performed. Twenty-four patients were identified as having fusiform aneurysms. Twenty-four aneurysms in these 24 patients were treated. The mean patient age was 59 years. There were 9 men and 15 women. Angiographic and clinical data (including the modified Rankin Scale [mRS] score) were recorded at the time of treatment and at follow-up. The aneurysms were located in the internal carotid artery in 8 patients (33.3%), middle cerebral artery in 8 patients (33.3%), anterior cerebral artery in 1 patient (4%), and vertebrobasilar circulation in 7 patients (29%). The aneurysms were smaller than 10 mm in 3 patients, 10-25 mm in 16 patients, and larger than 25 mm in 5 patients. The mean largest dimension diameter was 18 mm. RESULTS: Stent deployment was successful in all cases. The minor procedural morbidity was 4% (1 case). Morbidity and mortality related to aneurysm treatment were 4.2% and 4.2%, respectively. The mean mRS scores preoperatively and at clinical follow-up (median 6.0 months, mean 6.9 months) were 0.71 and 1.2, respectively (91.7% presented with an mRS score of 2 or better, and 79.2% had an mRS score of 2 or better at the 6.0-month follow-up). At clinical follow-up, 82.6% of patients were stable or had improved, 13.0% worsened, and 4.2% had died. Twenty-two (91.7%) of 24 patients had follow-up angiography available (mean follow-up time 6.3 months); 59% had excellent angiographic results (> 95% or complete occlusion), 31.8% had complete aneurysm occlusion, 27.3% had greater than 95% aneurysm occlusion, 18.2% had a moderate decrease in size (50%-95%), 4.5% had a minimal decrease in size (< 50%), 13.6% had not changed, and 4.5% had an increase in size. CONCLUSIONS: This series demonstrates that endovascular treatment of fusiform cerebral aneurysms with flow diversion was a safe and effective treatment. Procedural complications were low. Long-term morbidity and mortality rates were acceptable given the complex nature of these lesions.

A pilot study of focused ultrasound thalamotomy for essential tremor.

BACKGROUND: Recent advances have enabled delivery of high-intensity focused ultrasound through the intact human cranium with magnetic resonance imaging (MRI) guidance. This preliminary study investigates the use of transcranial MRI-guided focused ultrasound thalamotomy for the treatment of essential tremor. METHODS: From February 2011 through December 2011, in an open-label, uncontrolled study, we used transcranial MRI-guided focused ultrasound to target the unilateral ventral intermediate nucleus of the thalamus in 15 patients with severe, medication-refractory essential tremor. We recorded all safety data and measured the effectiveness of tremor suppression using the Clinical Rating Scale for Tremor to calculate the total score (ranging from 0 to 160), hand subscore (primary outcome, ranging from 0 to 32), and disability subscore (ranging from 0 to 32), with higher scores indicating worse tremor. We assessed the patients' perceptions of treatment efficacy with the Quality of Life in Essential Tremor Questionnaire (ranging from 0 to 100%, with higher scores indicating greater perceived disability). RESULTS: Thermal ablation of the thalamic target occurred in all patients. Adverse effects of the procedure included transient sensory, cerebellar, motor, and speech abnormalities, with persistent paresthesias in four patients. Scores for hand tremor improved from 20.4 at baseline to 5.2 at 12 months (P=0.001). Total tremor scores improved from 54.9 to 24.3 (P=0.001). Disability scores improved from 18.2 to 2.8 (P=0.001). Quality-of-life scores improved from 37% to 11% (P=0.001). CONCLUSIONS: In this pilot study, essential tremor improved in 15 patients treated with MRI-guided focused ultrasound thalamotomy. Large, randomized, controlled trials will be required to assess the procedure's efficacy and safety. (Funded by the Focused Ultrasound Surgery Foundation; ClinicalTrials.gov number, NCT01304758.).

Transcranial MR-guided focused ultrasound sonothrombolysis in the treatment of intracerebral hemorrhage.

Intracerebral hemorrhage remains a significant cause of morbidity and mortality. Current surgical therapies aim to use a minimally invasive approach to remove as much of the clot as possible without causing undue disruption to surrounding neural structures. Transcranial MR-guided focused ultrasound (MRgFUS) surgery is an emerging technology that permits a highly concentrated focal point of ultrasound energy to be deposited to a target deep within the brain without an incision or craniotomy. With appropriate ultrasound parameters it has been shown that MRgFUS can effectively liquefy large-volume blood clots through the human calvaria. In this review the authors discuss the rationale for using MRgFUS to noninvasively liquefy intracerebral hemorrhage (ICH), thereby permitting minimally invasive aspiration of the liquefied clot via a small drainage tube. The mechanism of action of MRgFUS sonothrombolysis; current investigational work with in vitro, in vivo, and cadaveric models of ICH; and the potential clinical application of this disruptive technology for the treatment of ICH are discussed.

Modern intraoperative imaging modalities for the vascular neurosurgeon treating intracerebral hemorrhage.

This paper reviews the current intraoperative imaging tools that are available to assist neurosurgeons in the treatment of intracerebral hemorrhage (ICH). This review shares the authors' experience with each modality and discusses the advantages, potential limitations, and disadvantages of each. Surgery for ICH is directed at blood clot removal, reduction of intracranial pressure, and minimization of secondary damage associated with hematoma breakdown products. For effective occlusion and safe obliteration of vascular anomalies associated with ICH, vascular neurosurgeons today require a thorough understanding of the various intraoperative imaging modalities available for obtaining real-time information. Use of one or more of these modalities may improve the surgeon's confidence during the procedure, the patient's safety during surgery, and surgical outcome. The modern techniques discussed include 1) indocyanine green-based video angiography, which provides real-time information based on high-quality images showing the residual filling of vascular pathological entities and the patency of blood vessels of any size in the surgical field; and 2) intraoperative angiography, which remains the gold standard intraoperative diagnostic test in the surgical management of cerebral aneurysms and arteriovenous malformations. Hybrid procedures, providing multimodality image-guided surgeries and combining endovascular with microsurgical strategies within the same surgical session, have become feasible and safe. Microdoppler is a safe, noninvasive, and reliable technique for evaluation of hemodynamics of vessels in the surgical field, with the advantage of ease of use. Intraoperative MRI provides an effective navigation tool for cavernoma surgery, in addition to assessing the extent of resection during the procedure. Intraoperative CT scanning has the advantage of very high sensitivity to acute bleeding, thereby assisting in the confirmation of the extent of hematoma evacuation and the extent of vascular anomaly resection. Intraoperative ultrasound aids navigation and evacuation assessment during intracerebral hematoma evacuation surgeries. It supports the concept of minimally invasive surgery and has undergone extensive development in recent years, with the quality of ultrasound imaging having improved considerably. Image-guided therapy, combined with modern intraoperative imaging modalities, has changed the fundamentals of conventional vascular neurosurgery by presenting real-time visualization of both normal tissue and pathological entities. These imaging techniques are important adjuncts to the surgeon's standard surgical armamentarium. Familiarity with these imaging modalities may help the surgeon complete procedures with improved safety, efficiency, and clinical outcome.

Safety and pharmacokinetics of sodium nitrite in patients with subarachnoid hemorrhage: a phase IIa study.

OBJECT: Intravenous sodium nitrite has been shown to prevent and reverse cerebral vasospasm in a primate model of subarachnoid hemorrhage (SAH). The present Phase IIA dose-escalation study of sodium nitrite was conducted to determine the compound's safety in humans with aneurysmal SAH and to establish its pharmacokinetics during a 14-day infusion. Methods In 18 patients (3 cohorts of 6 patients each) with SAH from a ruptured cerebral aneurysm, nitrite (3 patients) or saline (3 patients) was infused. Sodium nitrite and saline were delivered intravenously for 14 days, and a dose-escalation scheme was used for the nitrite, with a maximum dose of 64 nmol/kg/min. Sodium nitrite blood levels were frequently sampled and measured using mass spectroscopy, and blood methemoglobin levels were continuously monitored using a pulse oximeter. RESULTS: In the 14-day infusions in critically ill patients with SAH, there was no toxicity or systemic hypotension, and blood methemoglobin levels remained at 3.3% or less in all patients. Nitrite levels increased rapidly during intravenous infusion and reached steady-state levels by 12 hours after the start of infusion on Day 1. The nitrite plasma half-life was less than 1 hour across all dose levels evaluated after stopping nitrite infusions on Day 14. CONCLUSIONS: Previous preclinical investigations of sodium nitrite for the prevention and reversal of vasospasm in a primate model of SAH were effective using doses similar to the highest dose examined in the current study (64 nmol/kg/min). Results of the current study suggest that safe and potentially therapeutic levels of nitrite can be achieved and sustained in critically ill patients after SAH from a ruptured cerebral aneurysm.

Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance-guided focused ultrasound.

OBJECT: Intracerebral hemorrhage (ICH) is a major cause of death and disability throughout the world. Surgical techniques are limited by their invasive nature and the associated disability caused during clot removal. Preliminary data have shown promise for the feasibility of transcranial MR-guided focused ultrasound (MRgFUS) sonothrombolysis in liquefying the clotted blood in ICH and thereby facilitating minimally invasive evacuation of the clot via a twist-drill craniostomy and aspiration tube. METHODS AND RESULTS: In an in vitro model, the following optimum transcranial sonothrombolysis parameters were determined: transducer center frequency 230 kHz, power 3950 W, pulse repetition rate 1 kHz, duty cycle 10%, and sonication duration 30 seconds. Safety studies were performed in swine (n = 20). In a swine model of ICH, MRgFUS sonothrombolysis of 4 ml ICH was performed. Magnetic resonance imaging and histological examination demonstrated complete lysis of the ICH without additional brain injury, blood-brain barrier breakdown, or thermal necrosis due to sonothrombolysis. A novel cadaveric model of ICH was developed with 40-ml clots implanted into fresh cadaveric brains (n = 10). Intracerebral hemorrhages were successfully liquefied (> 95%) with transcranial MRgFUS in a highly accurate fashion, permitting minimally invasive aspiration of the lysate under MRI guidance. CONCLUSIONS: The feasibility of transcranial MRgFUS sonothrombolysis was demonstrated in in vitro and cadaveric models of ICH. Initial in vivo safety data in a swine model of ICH suggest the process to be safe. Minimally invasive treatment of ICH with MRgFUS warrants evaluation in the setting of a clinical trial.