A miniaturized ultrasonic micro-hole perforator for minimally invasive craniotomy

Objective: Micro-hole perforation on skull is urgently desired for minimally invasive insertion of micro-tools in brain for diagnostic or treatment purpose. However, a micro drill bit would easily fracture, making it difficult to safely generate a micro-hole on the hard skull. Methods: In this study, we present a method for ultrasonic vibration assisted micro-hole perforation on skull in a manner similar to subcutaneous injection on soft tissue. For this purpose, a high amplitude miniaturized ultrasonic tool with a 500 μm tip diameter micro-hole perforator was developed with simulation and experimental characterization. In-depth investigation of micro-hole generation mechanism was performed with systematic experiments on animal skull with a bespoke test rig; effects of vibration amplitude and feed rate on hole forming characteristics were systematically studied. It was observed that by exploiting skull bone's unique structural and material properties, the ultrasonic micro-perforator could locally damage bone tissue with micro-porosities, induce sufficient plastic deformation to bone tissue around the micro-hole and refrain elastic recovery after tool withdraw, generating a micro-hole on skull without material. Results : Under optimized conditions, high quality micro-holes could be formed on the hard skull with a force (< 1N) even smaller than that for subcutaneous injection on soft skin. Conclusion: This study would provide a safe and effective method and a miniaturized device for micro-hole perforation on skull for minimally invasive neural interventions

Imaging fast neural activity in the brain during epilepsy with electrical impedance tomography

Electrical impedance tomography (EIT) is a medical imaging technique which reconstructs images of the internal conductivity of an object using boundary measurements obtained by applying current through pairs of non-penetrating surface electrodes. EIT is able to image impedance changes which arise during neural activity at a high spatiotemporal resolution through the rat cerebral cortex and therefore represents a novel method for understanding neuronal network dynamics in epilepsy. Additionally, it holds therapeutic potential for improving the presurgical localisation of epileptogenic foci in individuals with drug-resistant epilepsy. This thesis was aimed at developing EIT for imaging epileptiform activity in vivo and assessing its potential for clinical use. Chapter 1 is a review of existing functional neuroimaging modalities, the principles of EIT and previous studies that have used EIT for imaging epileptic events. In Chapter 2, the safety of continuous current application to the rat cortical surface at 10-100 μA and 1725 Hz, parameters that are representative of fast neural EIT protocols, was verified by histological evaluation. Chapter 3 details the development of two acute rat models of focal epilepsy, the cortical and hippocampal epileptic afterdischarges models, for assessing the feasibility of imaging epileptiform activity with fast neural EIT using epicortical electrode arrays. In Chapter 4, EIT was used to image the propagation of ictal spike-and-wave activity through the cerebral cortex at a resolution of 2 ms and ≤300 µm. In order to enable imaging of epileptiform discharges in deeper subcortical structures, the optimal carrier frequency for current application was determined in Chapter 5. Results demonstrated that the maximal signal-to-noise ratio of fast neural impedance changes during ictal discharges is obtained at 1355 Hz. Finally, in Chapter 6, epileptiform activity in the hippocampus was imaged, with a localisation accuracy of ≤400 µm, using epicortical impedance measurements obtained at this optimised carrier frequency

Smoking and Second Hand Smoking in Adolescents with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children (CKiD) Cohort Study

The goal of this study was to determine the prevalence of smoking and second hand smoking [SHS] in adolescents with CKD and their relationship to baseline parameters at enrollment in the CKiD, observational cohort study of 600 children (aged 1-16 yrs) with Schwartz estimated GFR of 30-90 ml/min/1.73m2. 239 adolescents had self-report survey data on smoking and SHS exposure: 21 [9%] subjects had “ever” smoked a cigarette. Among them, 4 were current and 17 were former smokers. Hypertension was more prevalent in those that had “ever” smoked a cigarette (42%) compared to non-smokers (9%), p\u3c0.01. Among 218 non-smokers, 130 (59%) were male, 142 (65%) were Caucasian; 60 (28%) reported SHS exposure compared to 158 (72%) with no exposure. Non-smoker adolescents with SHS exposure were compared to those without SHS exposure. There was no racial, age, or gender differences between both groups. Baseline creatinine, diastolic hypertension, C reactive protein, lipid profile, GFR and hemoglobin were not statistically different. Significantly higher protein to creatinine ratio (0.90 vs. 0.53, p\u3c0.01) was observed in those exposed to SHS compared to those not exposed. Exposed adolescents were heavier than non-exposed adolescents (85th percentile vs. 55th percentile for BMI, p\u3c 0.01). Uncontrolled casual systolic hypertension was twice as prevalent among those exposed to SHS (16%) compared to those not exposed to SHS (7%), though the difference was not statistically significant (p= 0.07). Adjusted multivariate regression analysis [OR (95% CI)] showed that increased protein to creatinine ratio [1.34 (1.03, 1.75)] and higher BMI [1.14 (1.02, 1.29)] were independently associated with exposure to SHS among non-smoker adolescents. These results reveal that among adolescents with CKD, cigarette use is low and SHS is highly prevalent. The association of smoking with hypertension and SHS with increased proteinuria suggests a possible role of these factors in CKD progression and cardiovascular outcomes