Safety, Efficacy and Clinical Applications of Focused Ultrasound-Mediated Blood Brain Barrier Opening in Alzheimer's Disease: A Systematic Review.

Alzheimer's disease is a neurodegenerative disorder marked by cognitive decline and brain pathology involving amyloid plaques and neurofibrillary tangles. Current drug development focuses on disease-modifying therapies, primarily antibodies targeting amyloid or tau. However, the blood-brain barrier (BBB) poses a challenge for drug delivery to the brain. Pre- and early clinical data suggests that Focused Ultrasound (FUS) technology safely enhances BBB permeability without damaging brain tissue, enabling drug delivery. This systematic review discusses the application of FUS to open the BBB for the treatment of Alzheimer's disease (AD). We review the safety, efficacy, and potential biological effects of FUS-mediated BBB opening in AD patients.

Active MR-temperature feedback control of dynamic interstitial ultrasound therapy in brain: in vivo experiments and modeling in native and coagulated tissues.

PURPOSE: The recent clinical emergence of minimally invasive image-guided therapy has demonstrated promise in the management of brain metastasis, although control over the spatial pattern of heating currently remains limited. Based on experience in other organs, the delivery of high-intensity contact ultrasound energy from minimally invasive applicators can enable accurate spatial control of energy deposition, large treatment volumes, and high treatment rate. In this acute study, the feasibility of active MR-Temperature feedback control of dynamic ultrasound heat deposition for interstitial thermal ablation in brain was evaluatedin vivo. METHODS: A four-element linear ultrasound transducer (f=8.2 MHz) originally developed for transurethral ultrasound therapy was used in a porcine model for generating thermal ablations in brain interstitially. First, the feasibility of treating and retreating preciselyin vivo brain tissues using stationary (non-rotating device) ultrasound exposures was studied in two pigs. Experimental results were compared to numerical simulations for maximum surface acoustic intensities ranging from 5 to 20 W cm(-2). Second, active MRT feedback-controlled ultrasound treatments were performed in three pigs with a rotating device to coagulate target volumes of various shapes. The acoustic power and rotation rate of the device were adjusted in real-time based on MR-thermometry feedback control to optimize heat deposition at the target boundary. Modeling of in vivo treatments were performed and compared to observed experimental results. RESULTS: Overall, the time-space evolution of the temperature profiles observedin vivo could be well estimated from numerical simulations for both stationary and dynamic interstitial ultrasound exposures. Dynamic exposures performed under closed-loop temperature control enabled accurate elevation of the brain tissues within the targeted region above the 55 °C threshold necessary for the creation of irreversible thermal damage. Treatment volumes ranging from 1 to 9 cm3 were completed within 8±3 min with a radial targeting error<2 mm on average (treatment rate: 0.7±0.5 cm3/min). Tissue changes were visible on T1-weighted contrast-enhanced (T1w-CE) images immediately after treatment. These changes were also evident on T2-weighted (T2w) images acquired 2 h after the 1st treatment and correlated well with the MR-thermometry measurements. CONCLUSIONS: These results support the feasibility of active MRT feedback control of dynamic interstitial ultrasound therapy ofin vivo brain tissues and confirm the feasibility of using simulations to predict spatial heating patterns in the brain.

A psychiatric primer for the functional neurosurgeon.

There is increasing attention in the neurosurgical literature towards surgery, specifically deep brain stimulation (DBS), for psychiatric indications. Several positive trials have spurred intense investigation and research in this area, owing to rapid advances in the neurosciences. As a result, the scope of neurosurgical practice is evolving to now include disorders that weren't traditionally in the purview of the average functional neurosurgeon. Further, functional neurosurgeons are now being charged with taking care of patients as part of a multi-disciplinary group that includes psychologists and psychiatrists. As DBS for psychiatry continues to evolve, and as further indications are explored, it is incumbent on neurosurgeons who treat these disorders to familiarize themselves with current standards of diagnosis and treatment. Just as the movement disorder surgeon should be familiar with the biology, physiology, diagnosis and treatment of Parkinson's disease, so they should become familiar with similar aspects of commonly referred psychiatric conditions. Specifically, much of the interest in the DBS literature currently surrounds major depression, obsessive-compulsive disorder and Tourette's syndrome. Here, we review the epidemiology, diagnostic criteria, hypothesized neurocircuitry and current treatments, both medical and surgical of each of these conditions to serve as a centralized, introductory primer for the practicing functional neurosurgeon.