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With stroke currently the second-leading cause of death globally, and 87% of all strokes classified as ischemic, the development of a fast, accessible, cost-effective approach for imaging occlusive stroke could have a significant impact on health care outcomes and costs. Although clinical examination and standard computed tomography alone do not provide adequate information for understanding the complex temporal events that occur during an ischemic stroke, ultrasound imaging is well suited to the task of examining blood flow dynamics in real time and may allow for localization of a clot. A prototype bilateral 3-D ultrasound imaging system using two matrix array probes on either side of the head allows for correction of skull-induced aberration throughout two entire phased array imaging volumes. We investigated the feasibility of applying this custom correction technique in five healthy volunteers with Definity microbubble contrast enhancement. Subjects were scanned simultaneously via both temporal acoustic windows in 3-D color flow mode. The number of color flow voxels above a common threshold increased as a result of aberration correction in five of five subjects, with a mean increase of 33.9%. The percentage of large arteries visualized by 3-D color Doppler imaging increased from 46% without aberration correction to 60% with aberration correction., (Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

We present the first correction of refraction in three-dimensional (3D) ultrasound imaging using an iterative approach that traces propagation paths through a two-layer planar tissue model, applying Snell's law in 3D. This approach is applied to real-time 3D transcranial ultrasound imaging by precomputing delays offline for several skull thicknesses, allowing the user to switch between three sets of delays for phased array imaging at the push of a button. Simulations indicate that refraction correction may be expected to increase sensitivity, reduce beam steering errors, and partially restore lost spatial resolution, with the greatest improvements occurring at the largest steering angles. Distorted images of cylindrical lesions were created by imaging through an acrylic plate in a tissue-mimicking phantom. As a result of correcting for refraction, lesions were restored to 93.6% of their original diameter in the lateral direction and 98.1% of their original shape along the long axis of the cylinders. In imaging two healthy volunteers, the mean brightness increased by 8.3% and showed no spatial dependency.

Purpose: To investigate the performance of different reconstruction methods for monitoring temperature changes during transcranial magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS)., Materials and Methods: Four different temperature reconstruction methods were compared in volunteers (without heating) and patients undergoing transcranial MRgFUS: single baseline subtraction, multibaseline subtraction, hybrid single baseline/referenceless reconstruction, and hybrid multibaseline/referenceless reconstruction. Absolute temperature error and temporal temperature uncertainty of the different reconstruction methods were analyzed and compared., Results: Absolute temperature errors and temporal temperature uncertainty were highest with single baseline subtraction and lowest with hybrid multibaseline/referenceless reconstruction in all areas of the brain. Pulsation of the brain and susceptibility changes from tongue motion or swallowing caused substantial temperature errors when single or multibaseline subtraction was used, which were much reduced when the referenceless component was added to the reconstruction., Conclusion: Hybrid multibaseline/referenceless thermometry accurately measures temperature changes in the brain with fewer artifacts and errors due to motion than pure baseline subtraction methods., (Copyright © 2013 Wiley Periodicals, Inc.)

The goal was to test the effects of various combinations of pulse widths (PW) and duty cycles (DC) on high-intensity focused ultrasound (HIFU)-induced sonothrombolysis efficacy using an in vitro flow model. An ExAblate™ 4000 HIFU headsystem (InSightec, Inc., Israel) was used. Artificial blood clots were placed into test tubes inside a human calvarium and exposed to pulsatile flow. Four different duty cycles were tested against four different pulse widths. For all study groups, an increase in thrombolysis efficacy could be seen in association with increasing DC and/or PW (p < 0.0001). Using transcranial HIFU, significant thrombolysis can be achieved within seconds and without the use of lytic drugs in vitro. Longer duty cycles in combination with longer pulse widths seem to have the highest potential to optimize clot lysis efficacy.

Objective To evaluate the results of endoscopic transnasal resection of tuberculum sellae meningiomas (TSMs) as compared with transcranial approaches. Design We retrospectively analyzed five patients who underwent endoscopic endonasal resection of TSM and performed a comprehensive review of articles published between 2000 and 2012 describing the operative treatment of TSMs. Results Gross total resection (GTR) was achieved in four patients (80%). Transient diabetes insipidus occurred in three patients (60%). Preoperative visual field deficit resolved in all patients. Cerebrospinal fluid (CSF) leak occurred in one patient. Analysis of published studies included 1,026 transcranial and 144 transnasal cases. GTR was achieved in 85% of transcranial and 72% of transnasal cases. Visual field deficit improved in 65% of transcranial and 82% of transnasal cases. Rate of diabetes insipidus and CSF leak was higher in the transnasal series. Rate of GTR and visual improvement was higher in endoscopic endonasal as compared with microsurgical transnasal series. Conclusion The literature supports transsphenoidal surgery for the resection of TSMs with significant optic nerve compromise and limited lateral extension. This approach may have an equivalent if not superior outcome over transcranial surgery in visual outcome. CSF leaks are still a challenge but may improve with the use of vascularized nasoseptal flaps.

A woman with severe, refractory bulimia nervosa (BN) underwent treatment for comorbid depression using repetitive transcranial magnetic stimulation (rTMS) of the dorsomedial prefrontal cortex (DMPFC) using a novel technique. Unexpectedly, she showed a rapid, dramatic remission from BN. For 5 months pre-treatment, she had reported two 5-h binge-purge episodes per day. After rTMS session 2 the episodes stopped entirely for 1 week; after session 10 there were no further recurrences. Depression scores improved more gradually to remission at session 10. Full remission from depression and binge-eating/purging episodes was sustained more than 2 months after treatment completion. In neuroimaging studies, the DMPFC is important in impulse control, and is underactive in BN. DMPFC-rTMS may have enhanced the patient's ability to deploy previously acquired strategies to avoid binge-eating and purging via a reduction in her impulsivity. A larger sham-controlled trial of DMPFC-rTMS for binge-eating and purging behavior may be warranted.

We present an innovative microfluidic approach to transcranial delivery of small quantities of drugs in brief time pulses for neurobiological studies. The approach is based on a two-stage process of consecutive drug dispensing and delivery, demonstrated by a device featuring a fully planar design in which the microfluidic components are integrated in a single layer. This 2-D configuration offers ease in device fabrication and is compatible to diverse actuation schemes. A compliance-based and normally closed check valve is used to couple the microchannels that are responsible for drug dispensing and delivery. Brief pneumatic pressure pulses are used to mobilize buffer and drug solutions, which are injected via a cannula into brain tissue. Thus, the device can potentially allow transcranial drug delivery and can also be potentially extended to enable transdermal drug delivery. We have characterized the device by measuring the dispensed and delivered volumes under varying pneumatic driving pressures and pulse durations, the standby diffusive leakage, and the repeatability in the delivery of multiple pulses of drug solutions. Results demonstrate that the device is capable of accurately dispensing and delivering drug solutions 5 to 70 nL in volume within time pulses as brief as 50 ms, with negligible diffusive drug leakage over a practically relevant time scale. Furthermore, testing of pulsatile drug delivery into intact mouse brain tissue has been performed to demonstrate the potential application of the device to neurobiology.

Application of medicated oils on scalp had been practiced for centuries in the Ayurvedic system of medicine in diseases associated with the central nervous system. It is possible that the effectiveness of the therapy may be a result of targeted delivery of active compounds to the brain transcranially. Evidence also comes from two previous studies with positive results on brain targeted transcranial delivery of methadone base and diazepam on rat models. Possibility of transcranial drug delivery was investigated in healthy human volunteers using electroencephalography techniques by assessing the ability of transcranially administered diazepam in bringing about β activity in the electroencephalographic wave patterns and shortening of the sleep latency period. Non polar drug molecules dissolved in a non-aqueous sesame oil based vehicle is a significant feature in the transcranial dosage design. The study was under taken in two phases. In the Phase-I study scalp application of a single dose of 2 mg/3 ml of the oil was employed and in the Phase-II study repeat application of three doses 24 h apart were employed. Sleep latency changes were monitored with Multiple Sleep Latency Tests with 5 naps employing the standard electroencephalography, electroocculography and electromyography electrodes. Sleep onset was identified with the first epoch of any sleep stage non rapid eye movement 1, 2, 3, 4 or rapid eye movement using electroencephalography, electroocculography and electromyography criteria. In both phases of the study there was significant reduction in the sleep latencies. It was much more pronounced in the Phase-II study. None of the subjects however displayed beta activity in the electroencephalography. Sleep latency reduction following scalp application in both the phases are suggestive of transcranial migration of diazepam molecules to the receptor sites of the nerve tissue of the brain eliciting its pharmacological effect of sedation. Transcranial brain targeted dosage design is therefore feasible.

We sought to quantify the mean surface area of the exposed diaphragma sellae and the mean sellar volume in the subfrontal and anterolateral approaches to pituitary adenomas and to detail our expansion of the superficial and deep window in the anterolateral approach. We performed a retrospective data analysis and cadaveric study in a clinical and skull base laboratory. We studied eight patients who had anterolateral approach for transcranial resection of pituitary macroadenoma and seven cadaveric specimens. Main outcome measures were degree of tumor resection, cerebrospinal fluid (CSF) leak, cranial nerve outcome, and quantification of the exposed sella via the anterior (subfrontal) and anterolateral approach. We observed complete resection in one; visual outcome: stable in three, improved in four, worsened in one; CSF leakage in two; transient CN III palsy in three; mean surface area (mm(2)) of exposed diaphragma sellae,115.3 (subfrontal approach) versus 94.7 (anterolateral approach; p = 0.1); mean sellar volume (mm(3)) exposed, 224.8 (subfrontal approach) versus 569.3 (anterolateral approach; p < 0.0001). Our technical note supports the increased exposure of sellar volume via the anterolateral approach. Despite the relatively high complication rate, complex cranial surgeons should maintain the skills and knowledge of transcranial approaches. Indeed, the rapid expansion of transsphenoidal techniques will continue to decrease the number of cases but will also continue to increase the complexity of those adenomas that are referred for transcranial resection.

Objective: Various transcranial and transfacial approaches have been described and each claims to provide the best exposure to the anterior skull base. Similarly, each approach claims the best outcomes following the resection of anterior skull base malignancies. We have always advocated a combined neurorhinological approach for the management of paranasal sinus malignancies that infiltrate the skull base, such as esthesioneuroblastomas., Materials and Methods: At the outset, the technique was developed on cadaver specimens, imitating the limitations that might be imposed in the real-life situation when undertaking endoscopic sinus surgery. Additional exposure of the anterior cerebral fossa was achieved using a classical bifrontal approach. Starting with endoscopic or microscopic unroofing of the ethmoids, all relevant landmarks were identified. The frontal, sphenoid, and maxillary sinuses were then opened using endoscopic techniques., Results: The dissections proved that a broad exposure of the anterior skull base could be combined with clear endoscopic visualization of the nasal cavity and of all the paranasal sinuses from above. This facilitated complete eradication of lesions from the sinuses cavities, their walls, and the intracranial tumor., Discussion: The combined neurorhinosurgical transcranial approach to the anterior skull base and nasal and paranasal sinuses, avoiding trans-facial approaches, enables a multidiciplinary team to resect malignant tumors of the anterior skull base directly without unnecessary destruction of facial structures. It appears to provide better access than other more destructive methods like midfacial degloving or subfrontal approaches. Our single-stage approach also facilitates safe and effective reconstruction of the skull base. The technique can be employed for tumors of all sizes and is also used for orbital resections and decompression of the optic nerve and chiasma.