OBJECTIVE This study aimed to investigate the burden of CSF shunt failure and false alarms on pediatric patients with hydrocephalus, their caregivers, and the healthcare system. METHODS This retrospective longitudinal study examined pediatric patients who underwent CSF shunt procedures at Auckland City Hospital from January 2014 to December 2019. The study included patients aged 18 years or younger living within the hospital’s catchment area. Clinical encounters were recorded from the date of their first shunt insertion until November 1, 2023. Data collected included patient demographics, hospital admissions, acute and elective shunt-related imaging, clinic visits, surgery times, and symptom characteristics. Shunt-related admissions were categorized as either shunt failures or false alarms. RESULTS The cohort comprised 73 patients with follow-up periods ranging from 4 to 18 years. By the 1st year, 71% had been rehospitalized for shunt-related concerns, with 59% experiencing at least 1 false alarm and 38% experiencing at least 1 shunt failure. By the 4th year, 88% of patients had been rehospitalized for shunt-related concerns, 42% had experienced at least 3 false alarms, 60% had at least 1 shunt failure, and 25% had at least 3 shunt failures. The average accumulated hospital stay was 1 month for shunt failures and 2 weeks for false alarms, compared with 22 days for all other admissions. Frequent clinic interactions from multiple specialties highlighted the complex care needs of these patients. The timing of shunt failure or false alarm, but not symptom duration, significantly predicted their overall frequency. CONCLUSIONS This study details the chronic burden and complex care requirements for pediatric patients with CSF shunts. Shunt-related concerns significantly and disproportionately contribute to the patients’ total hospital interactions. The findings highlight the immediate clinical need for novel technologies to enable long-term and accurate detection of shunt failure to optimize patient care. Future efforts should focus on improving shunt systems to lower failure rates.

Abstract High Q coils are required by inductive power transfer (IPT) links to attain reasonable levels of power transfer especially for loosely coupled links such as those used for small, deeply implanted medical devices. However, the high Q feature makes IPT systems strongly dependent on operating frequency which must be matched in the primary and secondary resonant tanks. Consequently, power transfer is sensitive to resonant frequency shifts due to component aging and environmental factors. Here, a switched capacitor (SC) network is developed to maintain tight matching and enhance system robustness. The combination of high voltage and high frequency required to achieve power transfer to deeply implanted devices makes the SC network design challenging. High frequencies require small tuning capacitance and high voltage requires MOSFETS with large output capacitance (COSS) resulting in COSS having a significant effect on tuning frequency. This paper proposes a parameter design method incorporating COSS to eliminate the uncertainty of voltage related COSS. In the experiment, the SC network broadens the effective bandwidth from 37 to 585 kHz at the centre frequency of 6.50 MHz. Across a frequency sweep, the worst case in transfer power drop is −0.43 dB, which demonstrates sufficient immunity to parameter deviations.

Technological advancements in electronics and micromachining now allow the development of discrete wireless brain implantable micro-devices. Applications of such devices include stimulation or sensing and could enable direct placement near regions of interest within the brain without the need for electrode leads or separate battery compartments that are at increased risk of breakage and infection. Clinical use of leadless brain implants is accompanied by novel risks, such as migration of the implant. Additionally, the encapsulation material of the implants plays an important role in mitigating unwanted tissue reactions. These risks have the potential to cause harm or reduce the service of life of the implant. In the present study, we have assessed post-implantation tissue reaction and migration of borosilicate glass-encapsulated micro-implants within the cortex of the brain. Twenty borosilicate glass-encapsulated devices (2 × 3.5 × 20 mm) were implanted into the parenchyma of 10 sheep for 6 months. Radiographs were taken directly post-surgery and at 3 and 6 months. Subsequently, sheep were euthanized, and GFAP and IBA-1 histological analysis was performed. The migration of the implants was tracked by reference to two stainless steel screws placed in the skull. We found no significant difference in fluoroscopy intensity of GFAP and a small difference in IBA-1 between implanted tissue and control. There was no glial scar formation found at the site of the implant’s track wall. Furthermore, we observed movement of up to 4.6 mm in a subset of implants in the first 3 months of implantation and no movement in any implant during the 3–6-month period of implantation. Subsequent histological analysis revealed no evidence of a migration track or tissue damage. We conclude that the implantation of this discrete micro-implant within the brain does not present additional risk due to migration.

Background: Electrical stimulation applied to individual organs, peripheral nerves, or specific brain regions has been used to treat a range of medical conditions. In cardiovascular disease, autonomic dysfunction contributes to the disease progression and electrical stimulation of the vagus nerve has been pursued as a treatment for the purpose of restoring the autonomic balance. However, this approach lacks selectivity in activating function- and organ-specific vagal fibers and, despite promising results of many preclinical studies, has so far failed to translate into a clinical treatment of cardiovascular disease. Objective: Here we report a successful application of optogenetics for selective stimulation of vagal efferent activity in a large animal model (sheep). Methods and results: Twelve weeks after viral transduction of a subset of vagal motoneurons, strong axonal membrane expression of the excitatory light-sensitive ion channel ChIEF was achieved in the efferent projections innervating thoracic organs and reaching beyond the level of the diaphragm. Blue laser or LED light (>10 mW mm−2; 1 ms pulses) applied to the cervical vagus triggered precisely timed, strong bursts of efferent activity with evoked action potentials propagating at speeds of ∼6 m s−1. Conclusions: These findings demonstrate that in species with a large, multi-fascicled vagus nerve, it is possible to stimulate a specific sub-population of efferent fibers using light at a site remote from the vector delivery, marking an important step towards eventual clinical use of optogenetic technology for autonomic neuromodulation.

Implanted electronics require protection from the body's fluids to avoid moisture induced failure. This study presents an injection molded liquid crystal polymer (LCP) package to protect active implantable devices for chronic applications, such as in optogenetic research. The technology is applied and assessed through a custom package for a fully implantable optogenetic stimulation system, built on a versatile telemetry system that can incorporate additional stimulating and recording channels. An adapted quasi-steady state model predicts the lifetime of an enclosure, where the definition of the lifetime is the time before the internal relative humidity (RH) reaches a time constant, or 63%RH, a conservative limit to minimize the risk of corrosion. The lifetime of the LCP optogenetic device is 94 days, and can be extended to 326 days with the inclusion of 5% w/v silica gel desiccant. Samples of the LCP optogenetic device containing humidity sensors testing in saline at 38 °C support the RH change predictions. Desiccants inside the implant enclosure can store permeating moisture and prolong the life expectancy of LCP-based implants to years or decades. The results of this study demonstrates the feasibility of providing reliable protection for chronic optogenetic implants, and the technology can be transferred to other applications as an easily-manufactured, cost-effective, radiofrequency compatible alternative to hermetic packaging for chronic studies.

Pressure sensors are routinely used to monitor pressure in different regions of the body. These measurements are generally short-term as current sensors suffer from drift in accuracy, limiting practical use as a chronic implant. We report on the development of an implanted pressure reference for reducing sensor drift through recalibration, whilst the device is in situ. During a recalibration step, the mechanism generates a characteristic response into the pressure signal. The implanted sensor detects this response to perform on-board offset correction adjustments. Calibration is initiated with an external force, such as a simple finger pressing action. ANSYS modeling was used to adjust diaphragm dimensioning and deflection to induce a detectable correction signal. Testing was performed on a benchtop prototype with a ø10-mm titanium diaphragm. The accuracy of a recalibrated pressure sensor was ±0.15 mmHg. This is easily within the accuracy requirement for intracranial pressure monitoring of ±2 mmHg from the NS28 standard.

A number of cardiovascular diseases are characterised by increased levels of sympathetic nerve activity. However, the driving force behind this increase remains unclear. Studies have suggested that, in some of these diseases, reduced cerebral perfusion may cause a sympathetically mediated increase in arterial pressure in an effort to rectify the reduced cerebral perfusion e.g. Selfish Brain Hypothesis (Paton et al 2009). The objective of this research was to determine a) if physiological increases in intracranial pressure (ICP) will cause a reflex increase in arterial blood pressure to maintain cerebral perfusion pressure and b) if the response is driven by increased sympathetic nerve activity. Using an instrumented conscious sheep model, we measured intracranial pressure (subdural) and arterial pressure (carotid) using solid‐state Millar catheters. Saline was infused into the lateral ventricle through an intracerebroventricular catheter to increase intracranial pressure in a ramp‐like fashion. The ICP ramp was repeated after 2 hours of ganglionic blocker hexamethonium. The ramp increase in ICP led to a reflex linear increase in arterial pressure even when ICP remained within normal physiological levels (0–20 mmHg) (n=6, p<0.01). For example: a 10 mmHg increase in ICP lead to a 6.5 ± 1.4mmHg (n=6) increase in arterial pressure. Ganglionic blockade significantly reduced or abolished this increase in arterial pressure, suggesting mediation by increased sympathetic nerve activity. This is supported by preliminary direct renal sympathetic nerve recordings. We believe that this increase in arterial pressure is via an active control mechanism to try to correct reduced cerebral perfusion caused by the increased intracranial pressure. We speculate that alterations in this response may lead to increased sympathetic nerve activity and worsen prognosis in cardiovascular disease. Our preliminary data indicate that this response is active at physiological levels of intracranial pressure and not just at extreme levels where other reflexes such as the Cushing's response would be active. We propose that this response is an important novel addition to other known mechanisms protecting the brain from under‐perfusion. Support or Funding Information Supported by the Health Research Council of New Zealand

Feasibility of the novel utilization of a pressure switch mechanism for re-calibrating drifted implanted pressure sensors in-situ is demonstrated. We have designed and characterized the pressure response of a system, which can quantify the offset of a sensor after it has been implanted. The benchtop device is constructed of a 25 pm thick titanium diaphragm with 10 mm working diameter. An optimization algorithm detected a characteristic change in the pressure response produced by the activation of a pressure switch. The repeatability of detection across three sensors is within ±0.23 mmHg over 8 pressurization cycles.

Optogenetics allows control of neuronal activity with unprecedented spatiotemporal precision, and has enabled both significant advances in neuroscience and promising clinical prospects for some neurological, cardiac, and sensory disorders. The ability to chronically stimulate light-sensitive excitable cells is crucial for developing useful research tools and viable long-term treatment strategies. Popular optogenetic stimulation devices often rely on bench-top light-sources tethered via an optical fibre to the research animal, or significant componentry protruding externally from animal. These approaches are prone to infection, vulnerable to damage and restrict the experimental approaches that can be conducted. An ideal optogenetic stimulator would be contained entirely within the animal and provide precisely controlled optical output. However, existing prototypes of fully implantable devices rely on amplitude tuning of wireless power, which can vary strongly with environmental conditions. Here we show that pulse-width modulation (PWM) of the intensity of a light-emitting diode (LED) can enable control of photo-stimulation intensity equivalent to direct amplitude modulation. This result has significant implications for fully implantable light delivery tools, as PWM can be implemented with simple and miniaturized circuit architectures. We have modified a telemeter device previously developed by our group to include a small form-factor LED capable of generating sufficient optical power with manageable electrical power requirements and minimal heat generation. We have tested key device components in an in vitro mouse brain slice preparation and shown that pulse-width-modulation is an alternative method to modulate photo-stimulation intensity using a miniature circuit and providing easy control.

A relative deficiency in kidney oxygenation, i.e., renal hypoxia, may contribute to the initiation and progression of acute and chronic kidney disease. A critical barrier to investigate this is the lack of methods allowing measurement of the partial pressure of oxygen in kidney tissue for long periods in vivo. We have developed, validated, and tested a novel telemetric method that can do this. Here we provide details on the calibration, implantation, implementation for data recording, and reuse of this telemetry-based technology for measurement of medullary tissue oxygen tension in conscious, unrestrained rats. This technique provides an important additional tool for investigating the impact of renal hypoxia in biology and pathophysiology.

We hypothesised that both exogenous and endogenous angiotensin-II (AngII) can decrease the partial pressure of oxygen (PO2) in the renal cortex of unrestrained rats, which might in turn contribute to the progression of chronic kidney disease. Rats were instrumented with telemeters equipped with a carbon paste electrode for continuous measurement of renal cortical tissue PO2. The method reproducibly detected acute changes in cortical oxygenation induced by systemic hyperoxia and hypoxia. In conscious rats, renal cortical PO2 was dose-dependently reduced by intravenous AngII. Reductions in PO2 were significantly greater than those induced by equi-pressor doses of phenylephrine. In anaesthetised rats, renal oxygen consumption was not affected, and filtration fraction was increased only in the AngII infused animals. Oxygen delivery decreased by 50% after infusion of AngII and renal blood flow (RBF) fell by 3.3mlmin(-1). Equi-pressor infusion of phenylephrine did not significantly reduce RBF or renal oxygen delivery. Activation of the endogenous renin-angiotensin system in Cyp1a1Ren2 transgenic rats reduced cortical tissue PO2. This could be reversed within minutes by pharmacological angiotensin-II receptor type 1 (AT(1)R) blockade. Thus AngII is an important modulator of renal cortical oxygenation via AT(1) receptors. AngII had a greater influence on cortical oxygenation than did phenylephrine. This phenomenon appears to be attributable to the profound impact of AngII on renal oxygen delivery. We conclude that the ability of AngII to promote renal cortical hypoxia may contribute to its influence on initiation and progression of chronic kidney disease.

The brain is an exceptionally energetically demanding organ with little metabolic reserve, and multiple systems operate to protect and preserve the brain blood supply. But how does the brain sense its own perfusion? In this review, we discuss how the brain may harness the cardiovascular system to counter threats to cerebral perfusion sensed via intracranial pressure (ICP), cerebral oxygenation and ischaemia. Since the work of Cushing over 100 years ago, the existence of brain baroreceptors capable of eliciting increases in sympathetic outflow and blood pressure has been hypothesized. In the clinic, this response has generally been thought to occur only in extremis, to perfuse the severely ischaemic brain as cerebral autoregulation fails. We review evidence that pressor responses may also occur with smaller, physiologically relevant increases in ICP. The incoming brain oxygen supply is closely monitored by the carotid chemoreceptors; however, hypoxia and other markers of ischaemia are also sensed intrinsically by astrocytes or other support cells within brain tissue itself and elicit reactive hyperaemia. Recent studies suggest that astrocytic oxygen signalling within the brainstem may directly affect sympathetic nerve activity and blood pressure. We speculate that local cerebral oxygen tension is a major determinant of the mean level of arterial pressure and discuss recent evidence that this may be the case. We conclude that intrinsic intra- and extra-cranial mechanisms sense and integrate information about hypoxia/ischaemia and ICP and play a major role in determining the long-term level of sympathetic outflow and arterial pressure, to optimize cerebral perfusion.

Traumatic brain injury is a leading cause of death and permanent disability throughout the world. Over the past 15 years, basic science has made important advances in the understanding of this condition. These advances have not, however, translated into treatment of clinically proven benefit. It has been suggested that individualized care for brain injured patients should include improved monitoring of brain function. For clinical gains to be made, clinicians and researchers require appropriate diagnostic and monitoring tools. In this paper, we describe the novel method of acquiring temperature measurement from a pressure sensor. The method allows concurrent measurements of pressure and temperature. The temperature measurement has a sensitivity of 85.08 mV/°C, across the measurement range 20 °C-45 °C. The time constant of the temperature sensor is 610 ± 55 ms. The mean cross-sensitivity of the temperature signal to changes in pressure is 0.74 m°C/mmHg within the typical physiological pressure range (0-160 mmHg). A method to compensate for this pressure-related error is described. We have evaluated the accuracy of the temperature measurement and the long-term stability of 13 sensors over a period of 28 days. The mean difference between temperature measurements made from the sensors and those made from the reference sensor was <;0.2 °C.

In 1901, Cushing described a 'simple and definite law' where experimentally increasing ICP produces matching increases in BP, in order to maintain cerebral perfusion. In the ensuing years, the char...

To investigate the potential patient risk and interactions between a prototype implantable pressure monitoring device and a 3T clinical magnetic resonance imaging (MRI) machine to guide device design towards MR Conditional safety approval.

Hydrocephalus is the single most common pediatric neurosurgical problem worldwide. Current treatment of this life-threatening disorder involves diverting excess fluid from the ventricles of the brain via a prosthetic shunt. While many hydrocephalus sufferers rely heavily on their ventriculo-distal shunt to maintain a healthy intracranial pressure, shunts carry a high risk of failure. Current methods of assessing shunt patency are performed within the hospital, and many patients and their families feel bound to remaining within close proximity of a hospital in order to receive timely medical intervention in the event of a shunt failure. There is a need for a system which can detect shunt malfunction, simply and reliably. We present a novel method of obtaining flow measurements from a piezoresistive pressure transducer. This builds on an earlier development of obtaining simultaneous temperature and pressure measurement from the single ultra-miniature solid-state transducer. The flow measurement system is capable of measurements in the range 0-35 ml/h, typical of the fluid flow rates through a hydrocephalus shunt. Within the flow range 0-14 ml/hour the resolution is 2 ml/hour. For flow rates greater than 16 ml/hour the resolution is 5 ml/hour. Employing a thermal flow sensing technique, the maximum heating of the local fluid is 0.65 ± 0.02 °C. The flow signal is independent of ambient temperature. The sensor would be implanted in the shunt to allow the detection of the flow rate of fluid through it, enabling the clinician to measure the patency of a shunt in real time.

Recent advances in multimodal sensing technology and sensor miniaturization technologies are paving the way for a new era in physiological measurement. Traditional approaches have integrated several transducers on a single silicon chip or packaged several sensing elements within a biocompatible catheter. Thermal and electrical cross-talk between sensors, time-lag between parallel measurements, lower yields associated with the increased complexity, and restrictions on the minimum size are challenges presented by these approaches. We present an alternative method which enables simultaneous measurement of temperature, pressure and heart rate to be obtained from a single ultra-miniature solid-state transducer. For the first time multimodal data were obtained from the sensor located within the abdominal aortas of five rats. The catheter-tip sensor interfaces with a fully implanted and inductively powered telemetry device capable of operating for the lifetime of the animal. Results of this study demonstrate good agreement between the core-temperature measurement from the catheter-tip sensor and the reference sensor with mean difference between the two sensors of 0.03 °C ± 0.02 °C (n = 5, 7 days). Real-time data obtained in the undisturbed rat, revealed fluctuations associated with the rest-activity cycle, in temperature, mean arterial pressure and heart rate. The stress response was shown to elicit an elevation in the core temperature of 1.5 °C. This was heralded by an elevation in mean arterial pressure of 35 mmHg and heart rate of 160 bpm. Obtaining multiple parameters from a single transducer goes a considerable way towards overcoming challenges of the prior art.

We have developed a fully implantable telemetry device for use in mice.The telemeter is able to measure biopotential signals (EEG, EMG, ECG) at a sampling rate of 2000 Hz. The device has a volume of 1.45 cc with a unique contour design for subcutaneous implantation in mice over 20 gm in weight. A novel aspect to the device is that it contains no battery. Power to run the telemeter is provided by a wireless power pad placed under the cage of the animal. This provides continual operation of the telemeter (>90% data collection in a 24 hour period) during a range of normal animal behaviours. We have assessed the ability of this device to record biopotential signals for up to 3 months. We believe this technology offers new experimental paradigms to be explored.