Non-Invasive Neuromodulation Using Time-Varying Caloric Vestibular Stimulation.

Caloric vestibular stimulation (CVS) to elicit the vestibulo-ocular reflex has long been used in clinical settings to aid in the diagnosis of balance disorders and to confirm the absence of brainstem function. While a number of studies have hinted at the potential therapeutic applications of CVS, the limitations of existing devices have frustrated that potential. Current CVS irrigators use water or air during short-duration applications; however, this approach is not tenable for longer duration therapeutic protocols or home use. Here, we describe a solid-state CVS device we developed in order to address these limitations. This device delivers tightly controlled time-varying thermal waveforms, which can be programmed through an external control unit. It contains several safety features, which limit patients to the prescribed waveform and prevent the potential for temperature extremes. In this paper, we provide evidence that CVS treatment with time-varying, but not constant temperature waveforms, elicits changes in cerebral blood flow physiology consistent with the neuromodulation of brainstem centers, and we present results from a small pilot study, which demonstrate that the CVS can safely and feasibly be used longitudinally in the home setting to treat episodic migraine. Together, these results indicate that this solid-state CVS device may be a viable tool for non-invasive neuromodulation.

3-D transcranial ultrasound imaging with bilateral phase aberration correction of multiple isoplanatic patches: a pilot human study with microbubble contrast enhancement.

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.

Simultaneous bilateral real-time 3-d transcranial ultrasound imaging at 1 MHz through poor acoustic windows.

Ultrasound imaging has been proposed as a rapid, portable alternative imaging modality to examine stroke patients in pre-hospital or emergency room settings. However, in performing transcranial ultrasound examinations, 8%-29% of patients in a general population may present with window failure, in which case it is not possible to acquire clinically useful sonographic information through the temporal bone acoustic window. In this work, we describe the technical considerations, design and fabrication of low-frequency (1.2 MHz), large aperture (25.3 mm) sparse matrix array transducers for 3-D imaging in the event of window failure. These transducers are integrated into a system for real-time 3-D bilateral transcranial imaging-the ultrasound brain helmet-and color flow imaging capabilities at 1.2 MHz are directly compared with arrays operating at 1.8 MHz in a flow phantom with attenuation comparable to the in vivo case. Contrast-enhanced imaging allowed visualization of arteries of the Circle of Willis in 5 of 5 subjects and 8 of 10 sides of the head despite probe placement outside of the acoustic window. Results suggest that this type of transducer may allow acquisition of useful images either in individuals with poor windows or outside of the temporal acoustic window in the field.

Use of emergency department transcranial Doppler assessment of reperfusion after intravenous tPA for ischemic stroke.

BACKGROUND: Thrombolysis with intravenous recombinant tissue plasminogen activator (IV-tPA) has been associated with significant improvements in clinical outcomes when initiated within 3 h of symptom onset. Although adjunctive therapies for acute stroke have been developed, challenges remain in identifying appropriate patients and therapeutic end-point measurements. OBJECTIVE: To describe the use of transcranial Doppler (TCD) monitoring in the Emergency Department (ED) to guide the decision for advanced reperfusion strategies after failure of IV-tPA. CASE REPORT: A 75-year-old man presented to the ED within 50 min after the acute onset of right-sided hemiparesis and aphasia. After administration of IV-tPA, there was no immediate improvement in neurological symptoms. TCD performed in the ED demonstrated persistent left middle cerebral artery (MCA) occlusion. Based on this information, the patient received intra-arterial tPA followed by mechanical thrombectomy of the MCA occlusion, resulting in clinical improvement of the patient's right hemiparesis and aphasia. CONCLUSION: TCD is a feasible assessment tool for use in the ED to aid in diagnosis and to guide treatment decisions in patients with acute ischemic stroke, including those not responding to IV-tPA therapy.

The ultrasound brain helmet: new transducers and volume registration for in vivo simultaneous multi-transducer 3-D transcranial imaging.

Because stroke remains an important and time-sensitive health concern in developed nations, we present a system capable of fusing 3-D transcranial ultrasound volumes acquired from two sides of the head. This system uses custom sparse array transducers built on flexible multilayer circuits that can be positioned for simultaneous imaging through both temporal acoustic windows, allowing for potential registration of multiple real-time 3-D scans of cerebral vasculature. We examine hardware considerations for new matrix arrays-transducer design and interconnects-in this application. Specifically, it is proposed that SNR may be increased by reducing the length of probe cables. This claim is evaluated as part of the presented system through simulation, experimental data, and in vivo imaging. Ultimately, gains in SNR of 7 dB are realized by replacing a standard probe cable with a much shorter flex interconnect; higher gains may be possible using ribbon-based probe cables. In vivo images are presented, showing cerebral arteries with and without the use of microbubble contrast agent; they have been registered and fused using a simple algorithm which maximizes normalized cross-correlation.

Transcranial Doppler series part v: specialty applications.

Transcranial Doppler (TCD) is well known for its usefulness in diagnosing vasospasm in patients with subarachnoid hemorrhage and vasculopathy in children with sickle cell disease. However there are some lesser known TCD studies. Bubble studies detect right to left shunts. Head rotation studies evaluate for extrinsic compression of the vertebral arteries. CO2 challenge and breath holding studies evaluate vasomotor reserve. Reactive hyperemia studies help diagnose subclavian steal. Emboli monitoring detects any particulates that might be present in the cerebral blood flow.

Transcranial Doppler series part III: interpretation.

Transcranial Doppler (TCD) is a quick, non-invasive, and inexpensive way to evaluate the blood flow in the basal cerebral arteries. TCD is most commonly used to evaluate for vasospasm in patients with subarachnoid hemorrhage and for vasculopathy in children with sickle cell anemia. It may also be used to evaluate intracranial vessel narrowing and occlusion; collateral flow due to extracranial vessel occlusion, arteriovenous malformations, and cavernous carotid fistulas; and to help confirm cerebral circulatory arrest. Systolic upstroke, velocity, pulsatility index, and direction of flow aid in the interpretation of TCD.

Transcranial Doppler series part II: performing a transcranial Doppler.

Because of its portability, low cost, and quick, noninvasive nature, transcranial Doppler (TCD) has become a widely utilized exam to evaluate the basal cerebral arteries for various disease processes. The test is considered a "blind" and very difficult study by most vascular labs. Neurologists commonly order TCD, so the performance of it is slowly being adopted by neurodiagnostic labs. To perform a quality TCD, the technologist must be extremely skilled. The technologist must know where to place and how to angle the probe in order to insonate the vessels and must be familiar with the TCD equipment. The technologist should also have an understanding of what each vessel's waveform should look like under normal circumstances.

Transcranial Doppler series part IV: case studies.

Transcranial Doppler (TCD) is considered one of the most difficult ultrasound studies to perform. Knowledge of cerebral hemodynamics is essential to the interpretation of the TCD study. The most common uses for TCD are the evaluation for vasospasm after subarachnoid hemorrhage and for sickle cell vasculopathy. Other uses are the detection of vessel narrowing or occlusion, collateral flow secondary to internal carotid artery occlusion, arteriovenous malformations, and to confirm cerebral circulatory arrest. Case studies are presented to demonstrate the hemodynamic parameters that are used to interpret the TCD study.

The ultrasound brain helmet: feasibility study of multiple simultaneous 3D scans of cerebral vasculature.

We describe early stage experiments to test the feasibility of an ultrasound brain helmet to produce multiple simultaneous real-time three-dimensional (3D) scans of the cerebral vasculature from temporal and suboccipital acoustic windows of the skull. The transducer hardware and software of the Volumetrics Medical Imaging (Durham, NC, USA) real-time 3D scanner were modified to support dual 2.5 MHz matrix arrays of 256 transmit elements and 128 receive elements which produce two simultaneous 64 degrees pyramidal scans. The real-time display format consists of two coronal B-mode images merged into a 128 degrees sector, two simultaneous parasagittal images merged into a 128 degrees x 64 degrees C-mode plane and a simultaneous 64 degrees axial image. Real-time 3D color Doppler scans from a skull phantom with latex blood vessel were obtained after contrast agent injection as a proof of concept. The long-term goal is to produce real-time 3D ultrasound images of the cerebral vasculature from a portable unit capable of internet transmission thus enabling interactive 3D imaging, remote diagnosis and earlier therapeutic intervention. We are motivated by the urgency for rapid diagnosis of stroke due to the short time window of effective therapeutic intervention.

Real-time 3-D contrast-enhanced transcranial ultrasound and aberration correction.

Contrast-enhanced (CE) transcranial ultrasound (US) and reconstructed 3-D transcranial ultrasound have shown advantages over traditional methods in a variety of cerebrovascular diseases. We present the results from a novel ultrasound technique, namely real-time 3-D contrast-enhanced transcranial ultrasound. Using real-time 3-D (RT3D) ultrasound and microbubble contrast agent, we scanned 17 healthy volunteers via a single temporal window and nine via the suboccipital window and report our detection rates for the major cerebral vessels. In 71% of subjects, both of our observers identified the ipsilateral circle of Willis from the temporal window, and in 59% we imaged the entire circle of Willis. From the suboccipital window, both observers detected the entire vertebrobasilar circulation in 22% of subjects, and in 44%, the basilar artery. After performing phase aberration correction on one subject, we were able to increase the diagnostic value of the scan, detecting a vessel not present in the uncorrected scan. These preliminary results suggest that RT3D CE transcranial US and RT3D CE transcranial US with phase aberration correction have the potential to greatly impact the field of neurosonology.

Transcranial Doppler series. Part I: Understanding neurovascular anatomy.

Transcranial Doppler (TCD) is an ultrasound study that evaluates the blood flow in the brain and is considered by many to be the most difficult vascular study to perform. The circle of Willis is the group of vessels that are insonated with TCD. Knowledge of the arteries that comprise the circle of Willis, the origins of these vessels, and their vessel segments can make the test easier to perform. The technologist performing the TCD must also be aware that the circle of Willis is not complete in approximately 50% of all cases. Knowledge of the various anomalies will help a technologist understand why they may not be able to insonate a vessel.