Focused ultrasound in neuro-oncology: the role of the Focused Ultrasound Foundation in driving adoption and innovation.

The Focused Ultrasound Foundation was created to improve the lives of millions of people worldwide by accelerating the development of this noninvasive technology. The Foundation works to clear the path to global adoption by organizing and funding research, fostering collaboration, and building awareness among patients and professionals. Since its establishment in 2006, the Foundation has become the largest nongovernmental source of funding for focused ultrasound research. For more information, visit http://www.fusfoundation.org .

Applications of Focused Ultrasound in Cerebrovascular Diseases and Brain Tumors.

Oncology and cerebrovascular disease constitute two of the most common diseases afflicting the central nervous system. Standard of treatment of these pathologies is based on multidisciplinary approaches encompassing combination of interventional procedures such as open and endovascular surgeries, drugs (chemotherapies, anti-coagulants, anti-platelet therapies, thrombolytics), and radiation therapies. In this context, therapeutic ultrasound could represent a novel diagnostic/therapeutic in the armamentarium of the surgeon to treat these diseases. Ultrasound relies on mechanical energy to induce numerous physical and biological effects. The application of this technology in neurology has been limited due to the challenges with penetrating the skull, thus limiting a prompt translation as has been seen in treating pathologies in other organs, such as breast and abdomen. Thanks to pivotal adjuncts such as multiconvergent transducers, magnetic resonance imaging (MRI) guidance, MRI thermometry, implantable transducers, and acoustic windows, focused ultrasound (FUS) is ready for prime-time applications in oncology and cerebrovascular neurology. In this review, we analyze the evolution of FUS from the beginning in 1950s to current state-of-the-art. We provide an overall picture of actual and future applications of FUS in oncology and cerebrovascular neurology reporting for each application the principal existing evidences.

Transcranial magnetic resonance-guided focused ultrasound for temporal lobe epilepsy: a laboratory feasibility study.

OBJECTIVE In appropriate candidates, the treatment of medication-refractory mesial temporal lobe epilepsy (MTLE) is primarily surgical. Traditional anterior temporal lobectomy yields seizure-free rates of 60%-70% and possibly higher. The field of magnetic resonance-guided focused ultrasound (MRgFUS) is an evolving field in neurosurgery. There is potential to treat MTLE with MRgFUS; however, it has appeared that the temporal lobe structures were beyond the existing treatment envelope of currently available clinical systems. The purpose of this study was to determine whether lesional temperatures can be achieved in the target tissue and to assess potential safety concerns. METHODS Cadaveric skulls with tissue-mimicking gels were used as phantom targets. An ablative volume was then mapped out for a "virtual temporal lobectomy." These data were then used to create a target volume on the InSightec ExAblate Neuro system. The target was the amygdala, uncus, anterior 20 mm of hippocampus, and adjacent parahippocampal gyrus. This volume was approximately 5cm3. Thermocouples were placed on critical skull base structures to monitor skull base heating. RESULTS Adequate focusing of the ultrasound energy was possible in the temporal lobe structures. Using clinically relevant ultrasound parameters (power 900 W, duration 10 sec, frequency 650 kHz), ablative temperatures were not achieved (maximum temperature 46.1°C). Increasing sonication duration to 30 sec demonstrated lesional temperatures in the mesial temporal lobe structures of interest (up to 60.5°C). Heating of the skull base of up to 24.7°C occurred with 30-sec sonications. CONCLUSIONS MRgFUS thermal ablation of the mesial temporal lobe structures relevant in temporal lobe epilepsy is feasible in a laboratory model. Longer sonications were required to achieve temperatures that would create permanent lesions in brain tissue. Heating of the skull base occurred with longer sonications. Blocking algorithms would be required to restrict ultrasound beams causing skull base heating. In the future, MRgFUS may present a minimally invasive, non-ionizing treatment of MTLE.

Head phantoms for transcranial focused ultrasound.

PURPOSE: In the ongoing endeavor of fine-tuning, the clinical application of transcranial MR-guided focused ultrasound (tcMRgFUS), ex-vivo studies wlkiith whole human skulls are of great use in improving the underlying technology guiding the accurate and precise thermal ablation of clinically relevant targets in the human skull. Described here are the designs, methods for fabrication, and notes on utility of three different ultrasound phantoms to be used for brain focused ultrasound research. METHODS: Three different models of phantoms are developed and tested to be accurate, repeatable experimental options to provide means to further this research. The three models are a cadaver, a gel-filled skull, and a head mold containing a skull and filled with gel that mimics the brain and the skin. Each was positioned in a clinical tcMRgFUS system and sonicated at 1100 W (acoustic) for 12 s at different locations. Maximum temperature rise as measured by MR thermometry was recorded and compared against clinical data for a similar neurosurgical target. Results are presented as heating efficiency in units (°C/kW/s) for direct comparison to available clinical data. The procedure for casting thermal phantom material is presented. The utility of each phantom model is discussed in the context of various tcMRgFUS research areas. RESULTS: The cadaveric phantom model, gel-filled skull model, and full head phantom model had heating efficiencies of 5.3, 4.0, and 3.9 °C/(kW/s), respectively, compared to a sample clinical heating efficiency of 2.6 °C/(kW/s). In the seven research categories considered, the cadaveric phantom model was the most versatile, though less practical compared to the ex-vivo skull-based phantoms. CONCLUSIONS: Casting thermal phantom material was shown to be an effective way to prepare tissue-mimicking material for the phantoms presented. The phantom models presented are all useful in tcMRgFUS research, though some are better suited to a limited subset of applications depending on the researchers needs.

Intracranial inertial cavitation threshold and thermal ablation lesion creation using MRI-guided 220-kHz focused ultrasound surgery: preclinical investigation.

OBJECT: In biological tissues, it is known that the creation of gas bubbles (cavitation) during ultrasound exposure is more likely to occur at lower rather than higher frequencies. Upon collapsing, such bubbles can induce hemorrhage. Thus, acoustic inertial cavitation secondary to a 220-kHz MRI-guided focused ultrasound (MRgFUS) surgery is a serious safety issue, and animal studies are mandatory for laying the groundwork for the use of low-frequency systems in future clinical trials. The authors investigate here the in vivo potential thresholds of MRgFUS-induced inertial cavitation and MRgFUS-induced thermal coagulation using MRI, acoustic spectroscopy, and histology. METHODS: Ten female piglets that had undergone a craniectomy were sonicated using a 220-kHz transcranial MRgFUS system over an acoustic energy range of 5600-14,000 J. For each piglet, a long-duration sonication (40-second duration) was performed on the right thalamus, and a short sonication (20-second duration) was performed on the left thalamus. An acoustic power range of 140-300 W was used for long-duration sonications and 300-700 W for short-duration sonications. Signals collected by 2 passive cavitation detectors were stored in memory during each sonication, and any subsequent cavitation activity was integrated within the bandwidth of the detectors. Real-time 2D MR thermometry was performed during the sonications. T1-weighted, T2-weighted, gradient-recalled echo, and diffusion-weighted imaging MRI was performed after treatment to assess the lesions. The piglets were killed immediately after the last series of posttreatment MR images were obtained. Their brains were harvested, and histological examinations were then performed to further evaluate the lesions. RESULTS: Two types of lesions were induced: thermal ablation lesions, as evidenced by an acute ischemic infarction on MRI and histology, and hemorrhagic lesions, associated with inertial cavitation. Passive cavitation signals exhibited 3 main patterns identified as follows: no cavitation, stable cavitation, and inertial cavitation. Low-power and longer sonications induced only thermal lesions, with a peak temperature threshold for lesioning of 53°C. Hemorrhagic lesions occurred only with high-power and shorter sonications. The sizes of the hemorrhages measured on macroscopic histological examinations correlated with the intensity of the cavitation activity (R2 = 0.74). The acoustic cavitation activity detected by the passive cavitation detectors exhibited a threshold of 0.09 V·Hz for the occurrence of hemorrhages. CONCLUSIONS: This work demonstrates that 220-kHz ultrasound is capable of inducing a thermal lesion in the brain of living swines without hemorrhage. Although the same acoustic energy can induce either a hemorrhage or a thermal lesion, it seems that low-power, long-duration sonication is less likely to cause hemorrhage and may be safer. Although further study is needed to decrease the likelihood of ischemic infarction associated with the 220-kHz ultrasound, the threshold established in this work may allow for the detection and prevention of deleterious cavitations.

Alteration of basilar artery rho-kinase and soluble guanylyl cyclase protein expression in a rat model of cerebral vasospasm following subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The vasoconstrictor endothelin-1 (ET-1) has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). Previous results showed that CGS 26303, an endothelin converting enzyme (ECE) inhibitor, effectively prevented and reversed arterial narrowing in animal models of SAH. In the present study, we assessed the effect of CGS 26303 on neurological deficits in SAH rats. The involvement of vasoactive pathways downstream of ET-1 signaling in SAH was also investigated. METHODS: Sprague-Dawley rats were divided into five groups (n = 6/group): (1) normal control, (2) SAH, (3) SAH+vehicle, (4) SAH+CGS 26303 (prevention), and (5) SAH+CGS 26303 (reversal). SAH was induced by injecting autologous blood into cisterna magna. CGS 26303 (10 mg/kg) was injected intravenously at 1 and 24 hr after the initiation of SAH in the prevention and reversal protocols, respectively. Behavioral changes were assessed at 48 hr after SAH. Protein expression was analyzed by Western blots. RESULTS: Deficits in motor function were obvious in the SAH rats, and CGS 26303 significantly improved the rate of paraplegia. Expressions of rho-kinase-II and membrane-bound protein kinase C- δ and rhoA were significantly increased, while those of soluble guanylyl cyclase α 1 and ß 1 as well as protein kinase G were significantly decreased in the basilar artery of SAH rats. Treatment with CGS 26303 nearly normalized these effects. CONCLUSIONS: These results demonstrate that the rhoA/rho-kinase and sGC/cGMP/PKG pathways play pivotal roles in cerebral vasospasm after SAH. It also shows that ECE inhibition is an effective strategy for the treatment of this disease.

An updated assessment of the risk of radiation-induced neoplasia after radiosurgery of arteriovenous malformations.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is a minimally invasive technique employed in the treatment of intracranial arteriovenous malformations (AVMs). Patients experience a low incidence of complications following treatment. As long-term follow-up data became available, some late adverse effects have been reported. However, the exact incidence of radiosurgically induced neoplasia is not known. METHODS: At University of Virginia, imaging and clinical outcomes of 1309 patients with intracranial AVMs treated with GKRS have been reviewed. AVM patients underwent magnetic resonance imaging (MRI) every 6 months for 2 years and then annually following GKRS. When the nidi were no longer visible on magnetic resonance imaging, angiography was performed to verify the obliteration of AVMs. Patients were thereafter recommended to continue MRIs every 3-5 years to detect any long-term complications. A subset of 812, 358, and 78 patients had neuroimaging and clinical follow-up of at least 3, 10, and 15 years, respectively. RESULTS: The authors report the occurrence of 3 cases of radiosurgically induced neoplasia. More than 10 years after GKRS, 2 patients were found to have an incidental, uniformly enhancing, dural-based mass lesion near the site of the AVM with radiologic characteristics of a meningioma. As the lesions have shown no evidence of mass effect, they are being followed with serial neuroimaging. A third patient was found to have neurologic decline from a tumor in immediate proximity to an AVM previously treated with proton beam radiosurgery and GKRS. The patient underwent resection, demonstrating a high-grade glioma. The 3-, 10-, and 15-year incidence of a radiation-induced tumor is 0% (0/812), 0.3% (1/358), and 2.6% (2/78), respectively. The cumulative rate of radiosurgically induced tumors in those with a minimum of 10-year follow-up is 3 in 4692 person-years or 64 in 100,000 person-years. Thus, patients had a 0.64% chance of developing a radiation-induced tumor within ≥10 years following GKRS. If we calculate rates based on a subset of 78 patients with neuroimaging and clinical follow-up of ≤15 years, the cumulative rate was 3.4%. These are the second, third, and fifth reported cases of radiation-induced tumors following GKRS for an AVM. CONCLUSIONS: Although radiosurgery is generally considered a safe modality in the treatment of AVMs, radiation-induced neoplasia is a rare but serious adverse event. The possibility of GKRS-induced tumors underscores the necessity of long-term follow-up in AVM patients receiving radiosurgery.

Intraoperative ultrasound guidance for the placement of permanent ventricular cerebrospinal fluid shunt catheters: a single-center historical cohort study.

OBJECTIVE: Despite the frequency with which ventriculoperitoneal shunts are placed, ventricular catheter revision rates remains as high as 30%-40% at 1 year. Many neurosurgeons place ventricular catheters "blindly" depending on anatomical landmarks and personal experience. To determine whether intraoperative ultrasonography is beneficial for ventricular catheter placement, we performed a historical cohort study comparing shunts placed with intraoperative ultrasound (US) guidance to those placed blindly. METHODS: We reviewed all shunts placed by the Department of Neurosurgery at the University of Virginia from January 2005 to January 2007. During that time 211 patients underwent 242 shunts, with US use determined by surgeon's preference. Ninety-two shunts were placed by the use of US guidance, and 150 were placed without US. Adults received 176 shunts, 56 with US. Children received 66 shunts, 36 with US. Mean follow-up was 21.6 months. The primary end points examined were shunt revision, ventricular catheter revision (VCR), and acute VCR (revision within 1 week for an improperly-placed catheter). RESULTS: The use of US was associated with a statistically significant decrease in shunt revisions (odds ratio 0.492; 95% confidence interval 0.253-0.958). Of the shunts placed with US guidance, 21.7% required revision, compared with 29.3% without US. VCRs and acute VCRs occurred in 9.8% and 2.2%, respectively, for US shunts, compared with 14% and 5.3% without US. Pediatric revision rates were 30.6% with US versus 53.3% without, whereas adult rates were 16.1% and 23.3%, respectively. The benefit of US was more profound for occipital shunts. CONCLUSIONS: The use of US for the placement of permanent cerebrospinal fluid shunt catheters is associated with a decreased risk of shunt revision.

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.

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.

Trans-cranial focused ultrasound without hair shaving: feasibility study in an ex vivo cadaver model.

In preparing a patient for a trans-cranial magnetic resonance (MR)-guided focused ultrasound procedure, current practice is to shave the patient's head on treatment day. Here we present an initial attempt to evaluate the feasibility of trans-cranial focused ultrasound in an unshaved, ex vivo human head model. A human skull filled with tissue-mimicking phantom and covered with a wig made of human hair was sonicated using 220- and 710-kHz head transducers to evaluate the feasibility of acoustic energy transfer. Heating at the focal point was measured by MR proton resonance shift thermometry. Results showed that the hair had a negligible effect on focal spot thermal rise at 220 kHz and a 17% drop in temperature elevation when using 710 kHz.

Sliding dichotomy compared with fixed dichotomization of ordinal outcome scales in subarachnoid hemorrhage trials.

OBJECT: In randomized clinical trials of subarachnoid hemorrhage (SAH) in which the primary clinical outcomes are ordinal, it has been common practice to dichotomize the ordinal outcome scale into favorable versus unfavorable outcome. Using this strategy may increase sample sizes by reducing statistical power. Authors of the present study used SAH clinical trial data to determine if a sliding dichotomy would improve statistical power. METHODS: Available individual patient data from tirilazad (3552 patients), clazosentan (the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage trial [CONSCIOUS-1], 413 patients), and subarachnoid aneurysm trials (the International Subarachnoid Aneurysm Trial [ISAT], 2089 patients) were analyzed. Treatment effect sizes were examined using conventional fixed dichotomy, sliding dichotomy (logical or median split methods), or proportional odds modeling. Whether sliding dichotomy affected the difference in outcomes between the several age and neurological grade groups was also evaluated. RESULTS: In the tirilazad data, there was no significant effect of treatment on outcome (fixed dichotomy: OR = 0.92, 95% CI 0.80-1.07; and sliding dichotomy: OR = 1.02, 95% CI 0.87-1.19). Sliding dichotomy reversed and increased the difference in outcome in favor of the placebo over clazosentan (fixed dichotomy: OR = 1.06, 95% CI 0.65-1.74; and sliding dichotomy: OR = 0.85, 95% CI 0.52-1.39). In the ISAT data, sliding dichotomy produced identical odds ratios compared with fixed dichotomy (fixed dichotomy vs sliding dichotomy, respectively: OR = 0.67, 95% CI 0.55-0.82 vs OR = 0.67, 95% CI 0.53-0.85). When considering the tirilazad and CONSCIOUS-1 groups based on age or World Federation of Neurosurgical Societies grade, no consistent effects of sliding dichotomy compared with fixed dichotomy were observed. CONCLUSIONS: There were differences among fixed dichotomy, sliding dichotomy, and proportional odds models in the magnitude and precision of odds ratios, but these differences were not as substantial as those seen when these methods were used in other conditions such as head injury. This finding suggests the need for different outcome scales for SAH.

Potential intracranial applications of magnetic resonance-guided focused ultrasound surgery.

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) has the potential to create a shift in the treatment paradigm of several intracranial disorders. High-resolution MRI guidance combined with an accurate method of delivering high doses of transcranial ultrasound energy to a discrete focal point has led to the exploration of noninvasive treatments for diseases traditionally treated by invasive surgical procedures. In this review, the authors examine the current intracranial applications under investigation and explore other potential uses for MRgFUS in the intracranial space based on their initial cadaveric studies.

Transcranial magnetic resonance-guided focused ultrasound surgery for trigeminal neuralgia: a cadaveric and laboratory feasibility study.

OBJECT: Transcranial MR-guided focused ultrasound surgery (MRgFUS) is evolving as a treatment modality in neurosurgery. Until now, the trigeminal nerve was believed to be beyond the treatment envelope of existing high-frequency transcranial MRgFUS systems. In this study, the authors explore the feasibility of targeting the trigeminal nerve in a cadaveric model with temperature assessments using computer simulations and an in vitro skull phantom model fitted with thermocouples. METHODS: Six trigeminal nerves from 4 unpreserved cadavers were targeted in the first experiment. Preprocedural CT scanning of the head was performed to allow for a skull correction algorithm. Three-Tesla, volumetric, FIESTA MRI sequences were performed to delineate the trigeminal nerve and any vascular structures of the cisternal segment. The cadaver was positioned in a focused ultrasound transducer (650-kHz system, ExAblate Neuro, InSightec) so that the focus of the transducer was centered at the proximal trigeminal nerve, allowing for targeting of the root entry zone (REZ) and the cisternal segment. Real-time, 2D thermometry was performed during the 10- to 30-second sonication procedures. Post hoc MR thermometry was performed on a computer workstation at the conclusion of the procedure to analyze temperature effects at neuroanatomical areas of interest. Finally, the region of the trigeminal nerve was targeted in a gel phantom encased within a human cranium, and temperature changes in regions of interest in the skull base were measured using thermocouples. RESULTS: The trigeminal nerves were clearly identified in all cadavers for accurate targeting. Sequential sonications of 25-1500 W for 10-30 seconds were successfully performed along the length of the trigeminal nerve starting at the REZ. Real-time MR thermometry confirmed the temperature increase as a narrow focus of heating by a mean of 10°C. Postprocedural thermometry calculations and thermocouple experiments in a phantom skull were performed and confirmed minimal heating of adjacent structures including the skull base, cranial nerves, and cerebral vessels. For targeting, inclusion of no-pass regions through the petrous bone decreased collateral heating in the internal acoustic canal from 16.7°C without blocking to 5.7°C with blocking. Temperature at the REZ target decreased by 3.7°C with blocking. Similarly, for midcisternal targeting, collateral heating at the internal acoustic canal was improved from a 16.3°C increase to a 4.9°C increase. Blocking decreased the target temperature increase by 4.4°C for the same power settings. CONCLUSIONS: This study demonstrates focal heating of up to 18°C in a cadaveric trigeminal nerve at the REZ and along the cisternal segment with transcranial MRgFUS. Significant heating of the skull base and surrounding neural structures did not occur with implementation of no-pass regions. However, in vivo studies are necessary to confirm the safety and efficacy of this potentially new, noninvasive treatment.

Perforator aneurysms of the posterior circulation: case series and review of the literature.

INTRODUCTION: Posterior circulation perforator artery aneurysms are sparsely reported in the literature. The natural history of these rare lesions remains unclear and their diagnosis and management are not well-defined. METHODS: We reviewed our institution's medical records and performed a comprehensive literature search for cases of posterior circulation perforator aneurysms. Diagnostic imaging, management and clinical outcomes were the primary components of interest. RESULTS: Our first case was a 58-year-old patient who developed an infarct after attempted endovascular treatment of a basilar perforator artery aneurysm, the second case was a 55-year-old patient with a posterior cerebral artery perforator aneurysm who did well with conservative management and the third case was a 68-year-old patient who suffered an infarct after successful Onyx embolization of a superior cerebellar artery perforator aneurysm. From the literature we identified four case reports and four case series, all describing aneurysmal lesions of the basilar perforator arteries, giving a total of 17 cases including those from our institution. All cases presented with subarachnoid hemorrhage although 47% of initial vascular imaging studies failed to reveal the aneurysm. Cumulatively, 41% of patients were treated with microsurgery, 35% were treated with endovascular therapy and 24% were managed conservatively with subsequent spontaneous aneurysm resolution at a mean interval of 10 months after rupture. CONCLUSIONS: Perforator aneurysms of the posterior circulation are diagnostic and therapeutic challenges. Both microsurgical and endovascular treatment of posterior circulation perforator aneurysms are technically difficult, necessitating comprehensive management by an experienced cerebrovascular team.