1-hexyl n-cyanoacrylate compound (Neucrylate™ AN), a new treatment for berry aneurysm. III: Initial clinical results.

INTRODUCTION: As part of an institutionally approved research protocol, patients with cerebral berry aneurysm were enrolled in a clinical trial designed to evaluate the safety of the new moldable liquid embolic agent Neucrylate AN. METHODS: Twelve patients with aneurysms judged to be suboptimal for treatment by standard endovascular or surgical approaches were treated with Neucrylate AN. The agent was injected during temporary balloon occlusion at the neck of the aneurysm. The immediate angiographic percentage of aneurysm occlusion and periprocedural adverse events were assessed for each patient. Six-month follow-up angiographic studies were obtained for nine of the 12 patients. RESULTS: Ten of the 12 aneurysms treated (83%) were large to giant (>1.0 cm in diameter), nine (75%) were wide-necked (dome/neck ratio <2.0) and three (25%) were dissecting aneurysms. There were four (33%) periprocedural neurological events. Immediate aneurysm occlusion of >90% was obtained in nine of the 12 cases (75%). There were five recurrences (55.5%) at 6 months. CONCLUSION: This preliminary clinical series shows that it is feasible to achieve a high percentage of immediate aneurysm occlusion with limited patient morbidity and mortality in the setting of morphologically challenging aneurysms. These preliminary data support larger trials assessing the safety and efficacy of this agent.

Rapid intracranial clot removal with a new device: the alligator retriever.

BACKGROUND AND PURPOSE: Despite availability of an approved drug to treat acute cerebral ischemia, most patients with stroke do not realize a good outcome. A method that would rapidly increase or restore cerebral perfusion before irreversible cell death should improve patient outcomes. MATERIALS AND METHODS: We recently had the opportunity to treat 6 middle-aged-to-elderly patients who presented with signs and symptoms of acute cerebral ischemia, by mechanically removing their (predominantly) middle cerebral artery clots by using a new retrieval device that had been previously approved by the US Food and Drug Administration for intravascular retrieval of foreign bodies. During a 2-month period, the 6 patients were treated in 5 separate institutions. No patient had an unsuccessful attempt at clot removal. The cases were collected by personal communication with each operator. RESULTS: In all instances, use of the device resulted in rapid clot removal. Each patient had a large improvement in National Institutes of Health Stroke Scale score. Two of the 6 patients had experienced failure of another clot retrieval device, and 3 patients required no systemic thrombolytics, reducing the likelihood of one of the most feared complications of stroke therapy, intracranial hemorrhage. SUMMARY: We believe that use of this device may result in improved outcomes for patients with acute ischemic stroke. In our limited experience, it provided a rapid, safe, and effective means for achieving revascularization.

Analysis of complex framing coil stability in a wide-necked aneurysm model.

Appropriately sized 0.010- and 0.018-inch complex framing coils were placed in a wide-necked silicone aneurysm replica, and their stability was evaluated at variable physiologic flow rates using video recording. After detachment, the 0.010-inch coils demonstrated instability/prolapse that was proportional to flow rate. In contrast, 0.018-inch coils held their 3D configuration regardless of flow rate. The findings support the use of 0.018-inch coils (when possible) in aneurysms with unfavorable geometry, particularly in circulations with higher flow rates.

Complex curve microcatheters for berry aneurysm endovascular therapy.

By using images created with 3D rotational angiography or CT angiography as templates, it is possible to place anatomically correct curves on microcatheters, curves that reproduce the complex 3D vascular anatomy of individual patients. Catheters so curved conform to the anatomy of arteries leading to aneurysms and are less likely to be forced out of position as coil packing progresses.

Analysis of slipstream flow in a wide-necked basilar artery aneurysm: evaluation of potential treatment regimens.

SUMMARY: A replica of a lethal wide-necked basilar artery aneurysm was created by casting a deceased patient's brain vessels and then placing the replica in a circuit of pulsating optically clear non-Newtonian fluid. Individual fluid slipstreams were opacified with isobaric dyes, and images were recorded on film. Studies were completed on the vascular replica, then were repeated, first after placement of a stent across the aneurysm neck and then after placement of Guglielmi detachable coils into the aneurysm sac through the stent. The slipstreams entered the untreated aneurysm via the distal aneurysm neck (the inflow zone), impacting against the distal lateral aneurysm wall. When the stent was placed across the aneurysm neck, the slipstreams lost coherence and did not strike the aneurysm sidewall. Placing the coils further disturbed and reduced aneurysmal flow, especially when the coils filled the inflow zone at the distal lateral aneurysm sac.

Liquid acrylic adhesive agents in interventional neuroradiology.

Treating patients with brain arteriovenous malformations by the deposition of liquid embolic agents, particularly cyanoacrylates, requires judgment, technical expertise, and experience. Even though the first deposition of cyanoacrylate in human brain arteries occurred more than 25 years ago, the relative rarity of the disease and the high risk for complications has kept this procedure from being universally applied. Physicians are fortunate that, within the past year, new and better catheters have become available, and with the promise of approved cyanoacrylate devices that are now being evaluated, the future looks bright. This article reviews the history, chemistry, and uses of cyanoacrylate.

Flow dynamics in a lethal anterior communicating artery aneurysm.

We describe and analyze the flow dynamics in replicas of a human anterior communicating artery aneurysm. The replicas were placed in a circuit of pulsating non-Newtonian fluid, and flows were adjusted to replicate human physiologic parameters. Individual slipstreams were opacified with isobaric dyes, and images were recorded on film and by CT/MR angiography. When flow in the afferent (internal carotid) and efferent (anterior and middle cerebral) arteries was bilaterally equal, slipstreams rarely entered the aneurysm. When flow in either the afferent or efferent vessels was not symmetrical, however, slipstreams entered the aneurysm neck, impinged upon the aneurysm dome, and swirled within the aneurysm. Unequal flow in carotid or cerebral systems may be necessary to direct pathologic, fluid slipstreams into an aneurysm.

Analysis of slipstream flow in two ruptured intracranial cerebral aneurysms.

Replicas of ruptured posterior communicating and basilar artery aneurysms were created from cadaveric specimens and then were placed in a circuit of pulsating non-Newtonian fluid. Individual fluid slipstreams were opacified with isobaric dyes, and images were recorded on film. The slipstreams entered the distal aneurysm neck with impact against the distal lateral wall of the aneurysm. They then swirled slowly in a reverse vortical pattern within the aneurysm sac. Fluid exited the aneurysm at the proximal neck. The flow pattern clearly shows the impact zone of entering slipstreams (the point of aneurysm rupture) and provides information pertaining to aneurysm growth and formation.

An experimental and angiographic explanation of why ulcerated carotid bulbs embolize.

SUMMARY: The flow dynamics and pressure relationships in an ulcerated atherosclerotic carotid bulb obtained at post-mortem were studied and correlated with angiographic findings in a similar live patient. Using the lost wax technique, we created replicas of an ulcerated atherosclerotic carotid bulb from a fresh cadaver, and placed those replicas in a circuit of pulsating non-Newtonian fluid. Flow profiles were adjusted to replicate human physiologic flows, and flow rates of 400, 600, and 800 milliliters per minute were evaluated. In the replicas, the slipstreams were opacified with isobaric dyes, and images were recorded both on 35 mm film and on SuperVHS high speed video. Data were collected from needles placed radially in the common carotid artery, in the region of the maximal atherosclerotic narrowing, and in the internal carotid artery. Though pressure relationships could not be obtained in the live human for ethical reasons, angiography in a similar stenosis was evaluated for slipstream dynamics. The post-mortem replica had a 55% diameter stenosis (88% area stenosis) of the carotid bulb with a shallow 3 mm ulcer. Flow in the common carotid artery showed undisturbed slipstreams, but as these slipstreams entered the narrow bulb, they crowded together, accelerating dramatically, with a jet continuing distally beyond the maximal narrowing for at least 2 vessel diameters, where flow again became normal. As fluid entered the narrowed bulb, radial pressures decreased and within the ulcer a vortex circulation was found. Similar findings were observed on the angiographic images of the live patient. This combination of events, the slowly swirling fluid in the ulcer, which would allow platelet aggregates to form, and the intermittent low pressure of the Bernoulli effect which could pull the aggregates into the adjacent rapidly flowing blood may help explain how ulcerated carotid plaques lead to embolic stroke.

Pressure Measurements across Vascular Stenoses. Practice and Pitfalls.

SUMMARY: We describe and analyze pressure measurements across vascular stenoses in an atherosclerotic human carotid bulb replica using catheters of different diameters. Replicas of an atherosclerotic human carotid bulb were created using the lost wax technique, and were placed in a circuit of pulsating nonnewtonian fluid. Flows were adjusted to replicate human physiologic flow profiles. Common carotid artery total flow volume of 600 milliliters/minute was studied. A pressure recording device was calibrated; data were received from catheters placed longitudinally in the common carotid artery and internal carotid artery. The internal carotid artery pressures were obtained both through the stenosis as is usually performed in the angiography suite and through the vessel side-wall beyond the stenosis as a control. Internal carotid artery flow volumes were also measured with and without the catheter through the stenosis. Multiple pressure recordings and volume measurements were obtained in the replica using 7 French, 5 French, and 2.5 French catheters. Measurements of the replica showed a 58% diameter stenosis and an 89% area stenosis of the carotid bulb. All longitudinal pressure measurements in the common carotid artery agreed with control values regardless of the diameter of the catheter used. Pressure measurements were also in agreement with control values in the internal carotid artery using the 2.5 French catheter. However, when larger diameter catheters were employed, pressures measured with the catheter through the stenosis fell when compared to control values. Additionally, internal carotid artery flow volumes were also decreased when the larger diameter catheters were placed across the stenosis. Large diameter catheters when placed across vascular stenoses may cause an occlusive or near-occlusive state and artifactually increase the measured transstenotic vascular pressure gradient as well as decrease forward vascular flow.

Observations on control of N2 and N3 neck disease in squamous cell carcinoma of the head and neck by intra-arterial chemoradiation.

Patients with head and neck squamous cell cancer with N2 and N3 neck disease have a poor prognosis and are at risk to fail regionally despite combined surgery and radiation. Twenty-two patients with N2 and N3 neck disease (and T3-4 primaries) were treated with intra-arterial, high-dose cisplatin (CDDP), 150 mg/m2 per week for 4 weeks, and concurrent radiation. All patients were followed for at least 2 years or until death from any cause. Twenty patients had a complete response at the primary site. Two of the 20 with a complete response later had a neck recurrence and died. Five patients with palpable nodes after treatment underwent fine-needle aspiration (FNA), one of which was positive and two suggestive of cancer. Six neck dissections were performed in this group, only two of which had positive nodes. This chemoradiation protocol may offer reasonable control of N2 and N3 neck disease in advanced head and neck squamous cell cancer. Neck dissection appeared to be necessary in only those patients with nodes 8 weeks after treatment in whom FNA was positive or suggestive of cancer. Because of the relatively small size of this series, additional accrual and monitoring of such patients is planned.

An organ-preserving selective arterial chemotherapy strategy for head and neck cancer.

PURPOSE: Squamous cancer of the upper aerodigestive tract is a disheartening disease. Despite our best efforts, the long-term survival rate remains only 15% to 40%, and surgical cures often decrease the quality of life owing to the loss of swallowing and speech organs. A better understanding of tumor dynamics and the discovery that thiosulfate can neutralize cisplatin led us to develop a treatment plan that combines a rapid superselective high-dose intraarterial delivery of cisplatin (CDDP), simultaneous intravenous infusion of its antagonist, thiosulfate, and radiation therapy. METHODS: Patients with advanced head and neck squamous cancer were entered into the protocol after a multidisciplinary evaluation that included CT or MR imaging. Forty-two patients constituted the first cohort. After baseline angiography, an arterial acceptance test determined the maximum infusion rate that the tumor's nutrient artery would accept. CDDP was then infused at that rate, usually within 3 to 5 minutes, while the antagonist thiosulfate was given intravenously. In the second cohort of 85 patients with stage 3 or 4 previously untreated and unresectable disease, local radiation was added to the treatment plan. The radiation dose (180-200 cGy/d x 35) was delivered regionally on the basis of the known radiosensitizing effect of CDDP. RESULTS: Cohort 1 allowed us to develop the infusion technique and to establish a dose quantity and delivery frequency. When 150 mg/m2 was administered weekly for 4 weeks, no severe toxicity was found. In cohort 2, 72 (92%) of the remaining 78 patients had complete disappearance of their tumor. Seventeen severe toxic events were associated with 323 femoral catheterizations. One patient died of pulmonary embolus, precluding follow-up evaluation. Six patients had neurologic sequelae, three with transient and three with permanent strokes. CONCLUSION: Rapid superselective chemotherapy with CDDP combined with a circulatory systemic antagonist allowed delivery of an antitumoral drug directly into the lesion while protecting the kidneys and bone marrow from the agent's systemic effects. Use of a dose regimen of 150 mg CDDP/m2 per week for 4 weeks resulted in the disappearance of a large percentage of advanced squamous cancers.

Why do ulcerated atherosclerotic carotid artery plaques embolize? A flow dynamics study.

PURPOSE: We describe and analyze flow dynamics and pressure relationships in an ulcerated atherosclerotic human carotid bulb. METHODS: Replicas of an ulcerated atherosclerotic human carotid bulb were created using the lost wax technique. The resulting replicas were placed in a circuit of pulsating non-Newtonian fluid and flows were adjusted to replicate human physiological flow profiles. Common carotid artery total flow volumes of 400, 600, and 800 mL/min were studied. Slipstreams were opacified with isobaric dyes. Images were recorded on 35 mm film and on super VHS video. A pressure recording device was calibrated; data were received from needles placed radially and longitudinally in the common carotid artery, narrowed bulb/ulcer, and internal carotid artery. Multiple pressure recordings were obtained in the replicas. RESULTS: Measurements of the replica showed a 59% diameter stenosis and an 88% area stenosis of the carotid bulb with a shallow 3.3-mm ulcer. Analysis of flow in the common carotid artery showed undisturbed slipstreams, but as these streams entered the narrowed carotid bulb they crowded together and accelerated significantly. This accelerated jet continued for at least two vessel diameters into the more normal portions of the internal carotid artery, where flow remained disturbed peripherally and often assumed a helical pattern but was nonturbulent. As fluid entered the narrowed bulb, radial pressures decreased. Most important, at peak systole, lower radial pressure with a vortex circulation was found at the ulceration. CONCLUSION: This combination of events (ie, slowly swirling fluid within the ulcer, allowing platelet aggregates to form, and the intermittent Bernoulli effect, pulling the aggregates into the rapidly flowing blood) may help explain how ulcerated carotid plaques lead to embolic stroke.

Arteriovenous malformation model for training and research.

PURPOSE: To develop an arteriovenous malformation (AVM) model for teaching embolization techniques and for researching and developing new interventional devices. METHODS: Open pore cellulose sponges 2 to 5 cm in diameter were coated with a watertight elastomer. One to three afferent tubes (arteries) and one large efferent tube (vein) allowed insertion of the model into a circuit of pulsatile, flowing, non-Newtonian fluid. Using fluoroscopy and angiographic imaging, five neuroradiologists practiced occluding the AVM nidus with a variety of techniques and cyanoacrylate mixtures. RESULTS: The model appeared and behaved like a human brain AVM. Attempts to teach liquid adhesive techniques were successful, and though they were stressful for the trainee, failure had none of the disastrous sequelae that attend training with human subjects. CONCLUSION: The AVM training and research model is of value in introducing physicians to the techniques needed for endovascular cyanoacrylate therapy: it allows users to develop skills at their own rates, and permits safe "failure-mode" learning.

Flow dynamics in a fatal aneurysm of the basilar artery.

PURPOSE: To examine the flow dynamics in a fatal aneurysm of the basilar artery in humans. METHODS: We made transparent elastic replicas of the vertebrobasilar arteries of an elderly patient who died of a ruptured aneurysm in the basilar artery. Using non-Newtonian fluid, physiological pulsatile flow volumes and profiles, and isobaric dyes and particles, we observed and recorded the slipstreams as they entered the aneurysm while changing relative flow in the vertebral arteries. Finally, we placed clips on the aneurysm, leaving residuals (or dog-ears), and observed the slipstreams. RESULTS: The aneurysm originated laterally from the greater curvature of a tortuous basilar artery, measured 19 x 11 x 12 mm, and had a Murphy's teat at the apex, the rupture site. The neck measured 10 x 4 mm, about the diameter of the basilar artery. Slipstreams joined at the confluence of the vertebral arteries, formed helical flow patterns, and entered the aneurysm violently, striking the apex. They then passed proximally around the sac walls, then centrally, and finally reentered the basilar artery to pass distally. Altering the relative flows in the vertebral arteries could modify and prevent slipstream flow into the aneurysm. When a dog-ear was created by incorrect placement of an aneurysm clip, slipstreams entered only dog-ears that lay distal to the clip. Correctly placed clips excluded the aneurysm from the circulation, but did not return the flow dynamics to normal. CONCLUSION: High-velocity slipstreams strike aneurysms at their rupture site and have an impact on distal but not proximal dog-ears. Modifying relative flow may prevent aneurysmal filling. Further, a knowledge of flow dynamics may allow us to predict which aneurysms are at risk of enlarging and rupturing, and may help guide proper therapy.

Targeted infusions of supradose Cisplatin with systemic neutralization for carcinomas invading the temporal bone.

In an attempt to improve the dismal prognosis for patients with advanced cancer involving the temporal bone, a regional chemotherapy technique was piloted as part of the multimodality therapy for such patients. Rapid supradose cisplatin infusions selectively delivered to the lesion were given to 14 patients with carcinoma involving the temporal bone. Concurrent systemic cisplatin neutralization was achieved with sodium thiosulfate which permitted the use of cisplatin dose intensity regimens equivalent to fivefold the conventional amount. Four patients received chemotherapy alone, four had concomitant irradiation, and six had subsequent irradiation and/or temporal bone surgery. All patients tolerated the chemotherapy without significant complications or toxicity.All three of the patients with previously untreated disease responded to chemotherapy (2 Crs, 1 PR); three of the seven patients with recurrent disease responded to chemotherapy; and all four patients treated with chemoradiation had a complete response (including one patient with recurrent disease). The median follow-up time was 19 months (range, 5 to 63 months). Nine of the 14 patients are alive, including the 4 who were treated with targeted chemoradiation.The use of targeted high-dose chemotherapy for patients with malignant skull base lesions offers hope for improved outcome, particularly when this regimen is given simultaneously with radiation.

Design and evaluation of a flow phantom.

RATIONALE AND OBJECTIVES: We constructed a near-anatomically correct large-vessel phantom to perform repeatable flow dynamics research examinations by angiography, magnetic resonance (MR) angiography, and computed tomography (CT) angiography. METHODS: An internal carotid artery was constructed within a head phantom. The internal carotid artery branches into a middle and an anterior cerebral artery; the former trifurcates and ends in the superior sagittal sinus, and the latter ends in the inferior sagittal sinus. A transverse and sigmoid sinus drains the model. All four vessels connecting the arterial and venous vessels have variable flow-constricting ligatures placed around them. These ligatures are accessible on the skull surface. The skull cavity is filled with a silicone polymer that is isodense to brain on CT scans and isointense on most MR images. RESULTS: The flow in the phantom's vessels may be varied in a repeatable manner. Multiple scan sequences may be performed without the image degradation caused by patient motion. The homogeneity of the filler polymer allows visualization of flow-related artifacts that may be hidden by complex human anatomy. CONCLUSION: Preliminary images of each modality show promise for use of the phantom in imaging research on large-vessel flow dynamics.

Flow dynamics for radiologists. II. Practical considerations in the live human.

Although the rules about flows seem complex and even at times suggest chaos, some general principles can be extracted and used by the radiologist. Normal arteries damp disturbances, tolerate our catheters well, and generally cause the blood's slipstreams to swirl. It seems that the swirls and the energy that accompanies the passage of those swirls are prime determiners of the development of degenerative changes, most importantly of atherosclerosis and berry aneurysms. Knowing this, we now must direct our research to look beyond today's practical applications and this simplistic summary. Radiologists who trained during the angiography era are often incredulous when they see the richness of information found in physiologic flow models. For years, contrast agents have hidden the elegant complexity of blood flow. Now, however, we have two new powerful machines: the Doppler gray-scale ultrasound and the MR scanner. These machines routinely demonstrate flow data that we do not as yet use. As angiographers we have a natural and unconscious bias to make images produced by our new machines look like the classic angiogram. It is a powerful and pervasive bias. We still call angiography our "gold standard." We must overcome that bias. As valuable as angiography has been to radiology, it may no longer be our benchmark. A new standard is ready to be developed. The MR scanner even now not only allows calculation of global flow in vessels but also analyzes individual slipstreams. The images shown here are only the beginning. Keep our old mindset, and the limits and utility of the MR scanner will not be explored by radiologists. However, if we physicians, especially radiologists, reenter the field of fluid dynamics, all of science and our patients will benefit. We have broad shoulders to stand on and see into the future. Harvey, Hales, Galen, and Poiseuille: all were physicians; they added immeasurably to the foundations of rheology and our understanding of flowing blood. We must be willing to do likewise.