High-intensity focused ultrasound (HIFU) for dissolution of clots in a rabbit model of embolic stroke.

It is estimated that only 2-6% of patients receive thrombolytic therapy for acute ischemic stroke suggesting that alternative therapies are necessary. In this study, we investigate the potential for high intensity focused ultrasound (HIFU) to initiate thrombolysis in an embolic model of stroke. Iron-loaded blood clots were injected into the middle cerebral artery (MCA) of New Zealand White rabbits, through the internal carotid artery and blockages were confirmed by angiography. MRI was used to localize the iron-loaded clot and target the HIFU beam for treatment. HIFU pulses (1.5 MHz, 1 ms bursts, 1 Hz pulse repetition frequency, 20 s duration) were applied to initiate thrombolysis. Repeat angiograms and histology were used to assess reperfusion and vessel damage. Using 275 W of acoustic power, there was no evidence of reperfusion in post-treatment angiograms of 3 rabbits tested. In a separate group of animals, 415 W of acoustic power was applied and reperfusion was observed in 2 of the 4 (50%) animals treated. In the last group of animals, acoustic power was further increased to 550 W, which led to the reperfusion in 5 of 7 (∼70%) animals tested. Histological analysis confirmed that the sonicated vessels remained intact after HIFU treatment. Hemorrhage was detected outside of the sonication site, likely due to the proximity of the target vessel with the base of the rabbit skull. These results demonstrate the feasibility of using HIFU, as a stand-alone method, to cause effective thrombolysis without immediate damage to the targeted vessels. HIFU, combined with imaging modalities used to identify and assess stroke patients, could dramatically reduce the time to achieve flow restoration in patients thereby significantly increasing the number of patients which benefit from thrombolysis treatments

Acute ex vivo changes in brain white matter diffusion tensor metrics.

PURPOSE:Diffusion magnetic resonance imaging and tractography has an important role in the visualization of brain white matter and assessment of tissue microstructure. There is a lack of correspondence between diffusion metrics of live tissue, ex vivo tissue, and histological findings. The objective of this study is to elucidate this connection by determining the specific diffusion alterations between live and ex vivo brain tissue. This may have an important role in the incorporation of diffusion imaging in ex vivo studies as a complement to histological sectioning as well as investigations of novel neurosurgical techniques. METHODS:This study presents a method of high angular resolution diffusion imaging and tractography of intact and non-fixed ex vivo piglet brains. Most studies involving ex vivo brain specimens have been formalin-fixed or excised from their original biological environment, processes both of which are known to affect diffusion parameters. Thus, non-fixed ex vivo tissue is used. A region-of-interest based analysis of diffusion tensor metrics are compared to in vivo subjects in a selection of major white matter bundles in order to assess the translatability of ex vivo diffusion measurements. RESULTS:Tractography was successfully achieved in both in vivo and ex vivo groups. No significant differences were found in tract connectivity, average streamline length, or apparent fiber density. Significantly decreased diffusivity (mean, axial, and radial; p0.059) between groups were observed. CONCLUSION:This study validates the extrapolation of non-fixed fractional anisotropy measurements to live tissue and the potential use of ex vivo tissue for methodological development

Summary of recanalization rates following HIFU.

<p>Angiograms taken after clot injection and following HIFU treatment were compared and analyzed. Recanalization was noted if contrast agent was detected in the MCA following the treatment.</p

Schematic of experimental procedure.

<p>The rabbit is placed supine on a FUS positioning system and the head is coupled to the transducer with degassed water. The entire positioning system is placed inside the 3T MRI. The sonication is controlled by a computer software program which sets the function generator. The signal is amplified before reaching the matching circuit and transducer. Single point sonications are performed every 0.75 mm, moving distal to proximal and superior to inferior, to cover the entire clot surface.</p

HIFU (550 W) significantly enhances reperfusion.

<p>Reperfusion was expressed as a proportion of the total animals tested at each power and the values were compared using Fisher's exact test. HIFU treatment with increasing powers was statistically significant (*p<0.05).</p

Establishing a clinical service for the treatment of osteoid osteoma using magnetic resonance-guided focused ultrasound: overview and guidelines.

Recent studies have demonstrated the effectiveness of magnetic resonance-guided focused ultrasound (MRgFUS) in the treatment of osteoid osteoma (OO), a painful, benign bone tumor. As MRgFUS is a noninvasive and radiation-free treatment, it stands to replace the current standard of care, percutaneous radiofrequency, or laser thermal ablation. Within an institution, creation of a clinical OO MRgFUS treatment program would not only provide cutting edge medical treatment at the current time but would also establish the foundation for an MRgFUS clinical service to introduce treatments currently under development into clinical practice in the future. The purpose of this document is to provide information to facilitate creation of a clinical service for MRgFUS treatment of OO by providing (1) recommendations for the multi-disciplinary management of patients and (2) guidelines regarding current best practices for MRgFUS treatment. This paper will discuss establishment of a multi-disciplinary clinic, patient accrual, inclusion/exclusion criteria, diagnosis, preoperative imaging, patient preparation, anesthesia, treatment planning, targeting and treatment execution, complication avoidance, and patient follow-up to assure safety and effectiveness

HIFU (550 W) recanalizes ∼70% of blocked vessels with no arterial injury.

<p>In most animals treated with 550 W, recanalization, similar to what was achieved with 415 W was observed. A) In one animal, a greater extent of recanalization was achieved but was accompanied by an apparent tortuous MCA vessel suggesting some damage occurred to the MCA during sonication. B) Histological analysis from these animals revealed minor bleeding at the base of the brains; however the MCA appeared intact in these sections (inset). C) CD31 immunohistochemistry labeled endothelial cells and confirmed that the arteries and arterioles are viable in the sonicated regions. Scale bar (B inset, C, D) = 500 µm.</p