Protocol to Induce the Temporary Opening of the Blood-Brain Barrier with Short-Time Focused Ultrasound in Rats.

Brain neurodegenerative diseases are central nervous system (CNS) affections typically common in older adults. A new therapeutic approach for them consists of providing specific drugs to the CNS through blood circulation; however, the Blood-Brain Barrier (BBB) prevents almost 100% of neurotherapeutics from reaching the brain. There are indications that Focused Ultrasound (FUS), temporarily placed in the BBB, can achieve a controlled increase in temperature at its focus, allowing temporary, localized, and reversible opening of this barrier, which facilitates the temporary delivery of specific drugs. This work presents a FUS-based protocol for the local, temporary, and reversible opening of the BBB in Wistar rats. The proposed protocol specifies certain power, treatment times, and duty cycle to controllably increase the temperature at the region of interest, i.e., the substantia nigra. Numerical simulations using commercial software based on the finite element method were carried out to determine the optimal size of the craniotomies for nearly full-acoustic transmission. Experiments in rats were performed with the parameters used during computational simulations to determine the adequate opening of the BBB. For this, craniotomies of different sizes were made at coordinates of the substantia nigra, and FUS was applied from the exterior. The opening of the BBB was evaluated using Evans Blue (EB) as an indicator of the crossing of the dye from the blood vessels to brain tissue. Numerical simulations demonstrated a major distance reached by the ultrasound focus with a bigger diameter. Experimental results show the local, temporary, and reversible opening of the BBB through a 10 mm diameter craniotomy, which effectively allowed placing the ultrasound focus over the substantia nigra, unlike a 6 mm diameter craniotomy in which there is a deviation of the focus through that window. Moreover, from these results, it was also determined that the disruption of the BBB was reversible, with an opening duration of 6 h after FUS application. The experimental work developed in this study resulted in a minimally invasive method for the temporary opening of the BBB.

Personalized protocol and scoring scale for functional electrical stimulation of the hand: A pilot feasibility study.

BACKGROUND: Complex personalized Functional Electrical Stimulation (FES) protocols for calibrating parameters and electrode positioning have been proposed, most being time-consuming or technically cumbersome for clinical settings. Therefore, there is a need for new personalized FES protocols that generate comfortable, functional hand movements, while being feasible for clinical translation. OBJECTIVE: To develop a personalized FES protocol, comprising electrode placement and parameter selection, to generate hand opening (HO), power grasp (PW) and precision grip (PG) movements, and compare in a pilot feasibility study its performance to a non-personalized protocol based on standard FES guidelines. METHODS: Two FES protocols, one personalized (P1) and one non-personalized (P2), were used to produce hand movements in twenty-three healthy participants. FES-induced movements were assessed with a new scoring scale which comprises items for selectivity, functionality, and comfort. RESULTS: Higher FES-HSS scores were obtained with P1 for all movements: HO (p= 0.00013), PW (p= 0.00007), PG (p= 0.00460). Electrode placement time was significantly shorter for P2 (p= 0.00003). Comfort scores were similar for both protocols. CONCLUSIONS: The personalized protocol for electrode placement and parameter selection enabled functional FES-induced hand movements and presented advantages over a non-personalized protocol. This protocol warrants further investigation to confirm its suitability for developing upper-limb rehabilitation interventions with clinical translational potential.

Novel Cranial Implants of Yttria-Stabilized Zirconia as Acoustic Windows for Ultrasonic Brain Therapy.

Therapeutic ultrasound can induce changes in tissues by means of thermal and nonthermal effects. It is proposed for treatment of some brain pathologies such as Alzheimer's, Parkinson's, Huntington's diseases, and cancer. However, cranium highly absorbs ultrasound reducing transmission efficiency. There are clinical applications of transcranial focused ultrasound and implantable ultrasound transducers proposed to address this problem. In this paper, biocompatible materials are proposed for replacing part of the cranium (cranial implants) based on low porosity polycrystalline 8 mol% yttria-stabilized-zirconia (8YSZ) ceramics as acoustic windows for brain therapy. In order to assess the viability of 8YSZ implants to effectively transmit ultrasound, various 8YSZ ceramics with different porosity are tested; their acoustic properties are measured; and the results are validated using finite element models simulating wave propagation to brain tissue through 8YSZ windows. The ultrasound attenuation is found to be linearly dependent on ceramics' porosity. Results for the nearly pore-free case indicate that 8YSZ is highly effective in transmitting ultrasound, with overall maximum transmission efficiency of ≈81%, compared to near total absorption of cranial bone. These results suggest that 8YSZ polycrystals could be suitable acoustic windows for ultrasound brain therapy at 1 MHz.