Evaluation of laser bacterial anti-fouling of transparent nanocrystalline yttria-stabilized-zirconia cranial implant.

Background and objectiveThe development and feasibility of a novel nanocrystalline yttria-stabilized-zirconia (nc-YSZ) cranial implant has been recently established. The purpose of what we now call "window to the brain (WttB)" implant (or platform), is to improve patient care by providing a technique for delivery and/or collection of light into/from the brain, on demand, over large areas, and on a chronically recurring basis without the need for repeated craniotomies. WttB holds the transformative potential for enhancing light-based diagnosis and treatment of a wide variety of brain pathologies including cerebral edema, traumatic brain injury, stroke, glioma, and neurodegenerative diseases. However, bacterial adhesion to the cranial implant is the leading factor for biofilm formation (fouling), infection, and treatment failure. Escherichia coli (E. coli), in particular, is the most common isolate in gram-negative bacillary meningitis after cranial surgery or trauma. The transparency of our WttB implant may provide a unique opportunity for non-invasive treatment of bacterial infection under the implant using medical lasers.Study design/materials and methodsA drop of a diluted overnight culture of BL21-293 E. coli expressing luciferase was seeded between the nc-YSZ implant and the agar plate. This was followed by immediate irradiation with selected laser. After each laser treatment the nc-YSZ was removed, and cultures were incubated for 24 hours at 37 °C. The study examined continuous wave (CW) and pulsed wave (PW) modes of near-infrared (NIR) 810 nm laser wavelength with a power output ranging from 1 to 3 W. During irradiation, the temperature distribution of nc-YSZ surface was monitored using an infrared thermal camera. Relative luminescence unit (RLU) was used to evaluate the viability of bacteria after the NIR laser treatment.ResultsAnalysis of RLU suggests that the viability of E. coli biofilm formation was reduced with NIR laser treatment when compared to the control group (P < 0.01) and loss of viability depends on both laser fluence and operation mode (CW or PW). The results demonstrate that while CW laser reduces the biofilm formation more than PW laser with the same power, the higher surface temperature of the implant generated by CW laser limits its medical efficacy. In contrast, with the right parameters, PW laser produces a more moderate photothermal effect which can be equally effective at controlling bacterial growth.ConclusionsOur results show that E. coli biofilm formation across the thickness of the nc-YSZ implant can be disrupted using NIR laser treatment. The results of this in vitro study suggest that using nc-YSZ as a cranial implant in vivo may also allow for locally selective, non-invasive, chronic treatment of bacterial layers (fouling) that might form under cranial implants, without causing adverse thermal damage to the underlying host tissue when appropriate laser parameters are used. Lasers Surg. Med. 48:782-789, 2016. © 2016 Wiley Periodicals, Inc

Characterization of ageing resistant transparent nanocrystalline yttria-stabilized zirconia implants.

The "Window to the Brain" is a transparent cranial implant under development, based on nanocrystalline yttria-stabilized zirconia (nc-YSZ) transparent ceramic material. Previous work has demonstrated the feasibility of this material to facilitate brain imaging over time, but the long-term stability of the material over decades in the body is unknown. In this study, the low-temperature degradation (LTD) of nc-YSZ of 3, 6, and 8 mol % yttria is compared before and after accelerated ageing treatments following ISO standards for assessing the ageing resistance of zirconia ceramics. After 100 hr of accelerated ageing (equivalent to many decades of ageing in the body), the samples do not show any signs of phase transformation to monoclinic by X-ray diffraction and micro-Raman spectroscopy. Moreover, the mechanical hardness of the samples did not decrease, and changes in optical transmittance from 500 to 1000 nm due to ageing treatments was minimal (below 3% for all samples), and unlikely to be due to phase transformation of surface crystals to monoclinic. These results indicate the nc-YSZ has excellent ageing resistance and can withstand long-term implantation conditions without exhibiting LTD

Enhanced near infrared optical access to the brain with a transparent cranial implant and scalp optical clearing.

We report on the enhanced optical transmittance in the NIR wavelength range (900 to 2400 nm) offered by a transparent Yttria-stabilized zirconia (YSZ) implant coupled with optical clearing agents (OCAs). The enhancement in optical access to the brain is evaluated upon comparing ex-vivo transmittance measurements of mice native skull and the YSZ cranial implant with scalp and OCAs. An increase in transmittance of up to 50% and attenuation lengths of up to 2.4 mm (i.e., a five-fold increase in light penetration) are obtained with the YSZ implant and the OCAs. The use of this ceramic implant and the biocompatible optical clearing agents offer attractive features for NIR optical techniques for brain theranostics

Selection of endurance capabilities and the trade-off between pressure and volume in the evolution of the human heart

Chimpanzees and gorillas, when not inactive, engage primarily in short bursts of resistance physical activity (RPA), such as climbing and fighting, that creates pressure stress on the cardiovascular system. In contrast, to initially hunt and gather and later to farm, it is thought that preindustrial human survival was dependent on lifelong moderate-intensity endurance physical activity (EPA), which creates a cardiovascular volume stress. Although derived musculoskeletal and thermoregulatory adaptations for EPA in humans have been documented, it is unknown if selection acted similarly on the heart. To test this hypothesis, we compared left ventricular (LV) structure and function across semiwild sanctuary chimpanzees, gorillas, and a sample of humans exposed to markedly different physical activity patterns. We show the human LV possesses derived features that help augment cardiac output (CO) thereby enabling EPA. However, the human LV also demonstrates phenotypic plasticity and, hence, variability, across a wide range of habitual physical activity. We show that the human LV’s propensity to remodel differentially in response to chronic pressure or volume stimuli associated with intense RPA and EPA as well as physical inactivity represents an evolutionary trade-off with potential implications for contemporary cardiovascular health. Specifically, the human LV trades off pressure adaptations for volume capabilities and converges on a chimpanzee-like phenotype in response to physical inactivity or sustained pressure loading. Consequently, the derived LV and lifelong low blood pressure (BP) appear to be partly sustained by regular moderate-intensity EPA whose decline in postindustrial societies likely contributes to the modern epidemic of hypertensive heart disease

A pilot study evaluating use of a computer-assisted neurorehabilitation platform for upper-extremity stroke assessment

<p>Abstract</p> <p>Background</p> <p>There is a need to develop cost-effective, sensitive stroke assessment instruments. One approach is examining kinematic measures derived from goal-directed tasks, which can potentially be sensitive to the subtle changes in the stroke rehabilitation process. This paper presents the findings from a pilot study that uses a computer-assisted neurorehabilitation platform, interfaced with a conventional force-reflecting joystick, to examine the assessment capability of the system by various types of goal-directed tasks.</p> <p>Methods</p> <p>Both stroke subjects with hemiparesis and able-bodied subjects used the force-reflecting joystick to complete a suite of goal-directed tasks under various task settings. Kinematic metrics, developed for specific types of goal-directed tasks, were used to assess various aspects of upper-extremity motor performance across subjects.</p> <p>Results</p> <p>A number of metrics based on kinematic performance were able to differentiate subjects with different impairment levels, with metrics associated with accuracy, steadiness and speed consistency showing the best capability. Significant differences were also shown on these metrics between various force field settings.</p> <p>Conclusion</p> <p>The results support the potential of using UniTherapy software with a conventional joystick system as an upper-extremity assessment instrument. We demonstrated the ability of using various types of goal-directed tasks to distinguish between subjects with different impairment levels. In addition, we were able to show that different force fields have a significant effect on the performance across subjects with different impairment levels in the trajectory tracking task. These results provide motivation for studies with a larger sample size that can more completely span the impairment space, and can use insights presented here to refine considerations of various task settings so as to generalize and extend our conclusions.</p

The Feasibility of a Transparent Cranial Implant for Chronic Structural and Functional Brain Imaging

A variety of medical conditions (e.g., traumatic brain injury, cerebral edema, stroke, brain tumors) necessitate surgical craniectomy to access the brain, followed by the placement of a cranial implant to replace the excised cranial bone. Cranial implants provide mechanical protection to the brain, and are made from a variety of materials ranging from polymers to metals and ceramics. Despite this variety of implant options, all current cranial implants for patient use lack optical transparency which could allow for brain imaging or therapy without additional open-skull procedures. The “Window to the Brain” is a novel transparent cranial implant made from a tough, biocompatible ceramic called nanocrystalline-Yttria Stabilized Zirconia. Preliminary studies have shown that this material allows for acute brain imaging in vivo, but its suitability for chronic use has not been established. In this dissertation, I investigated (1) the stability of the optical access provided by the window for chronic brain imaging in vivo; (2) functional and structural imaging techniques across the window; (3) laser bacterial antifouling strategies for use with the window; (4) characterization of the window’s optical properties which impact imaging. This work provides answers to some of the key remaining questions regarding the feasibility of a transparent cranial implant for chronic structural and functional brain imaging based on nc-YSZ

The Feasibility of a Transparent Cranial Implant for Chronic Structural and Functional Brain Imaging

A variety of medical conditions (e.g., traumatic brain injury, cerebral edema, stroke, brain tumors) necessitate surgical craniectomy to access the brain, followed by the placement of a cranial implant to replace the excised cranial bone. Cranial implants provide mechanical protection to the brain, and are made from a variety of materials ranging from polymers to metals and ceramics. Despite this variety of implant options, all current cranial implants for patient use lack optical transparency which could allow for brain imaging or therapy without additional open-skull procedures. The “Window to the Brain” is a novel transparent cranial implant made from a tough, biocompatible ceramic called nanocrystalline-Yttria Stabilized Zirconia. Preliminary studies have shown that this material allows for acute brain imaging in vivo, but its suitability for chronic use has not been established. In this dissertation, I investigated (1) the stability of the optical access provided by the window for chronic brain imaging in vivo; (2) functional and structural imaging techniques across the window; (3) laser bacterial antifouling strategies for use with the window; (4) characterization of the window’s optical properties which impact imaging. This work provides answers to some of the key remaining questions regarding the feasibility of a transparent cranial implant for chronic structural and functional brain imaging based on nc-YSZ