Development of a Tetherless Bioimpedance Device That Uses Morphologic Changes to Predict Blood Flow Restrictions Mimicking Peripheral Artery Disease Progression.

A tetherless multi-targeted bioimpedance device was designed, modeled, built, and tested for measuring arterial pulse and, using morphological analysis, its potential for monitoring blood flow restrictions that mimic Peripheral Artery Disease (PAD) was assessed across multiple peripheral arteries. Specifically, we first developed a small form factor, tetherless, bioimpedance device, based on high-frequency structure simulator (HFSS) simulations. After designing and building the device we then tested it in vivo on human subjects on multiple arteries and found that we did not need to modify the gain on the device compared to the bench top system. Further, it was found that changes in the morphology of the bioimpedance signal over time, depicted through the ratio of the first and second harmonic in the signal frequency, could be used to predict blood flow restrictions that mimic peripheral artery disease (PAD). The HFSS simulations helped guide the modulation frequency selection and the placement of the bioimpedance electrodes. We built the device and compared it to two commercially available bioimpedance devices and it was shown to demonstrate a distinct advantage in its multi-target capability, enabling more accurate pulse measurements from different arteries without the need for tuning the circuit for each artery. Comparing the ratio of the 1st and 2nd harmonics as a function of the blood flow restriction, the two commercial devices showed a maximum error across arteries of between 22% and 27% depending on the measurement location, whereas our system consistently displayed a stable value of just below 4%. With this system, there is the potential for comprehensive and personalized medical examinations for PAD at the point of care (POC).

Arterial Pulse Wave Velocity Signal Reconstruction Using Low Sampling Rates.

Pulse Wave Velocity (PWV) analysis is valuable for assessing arterial stiffness and cardiovascular health and potentially for estimating blood pressure cufflessly. However, conventional PWV analysis from two transducers spaced closely poses challenges in data management, battery life, and developing the device for continuous real-time applications together along an artery, which typically need data to be recorded at high sampling rates. Specifically, although a pulse signal consists of low-frequency components when used for applications such as determining heart rate, the pulse transit time for transducers near each other along an artery takes place in the millisecond range, typically needing a high sampling rate. To overcome this issue, in this study, we present a novel approach that leverages the Nyquist-Shannon sampling theorem and reconstruction techniques for signals produced by bioimpedance transducers closely spaced along a radial artery. Specifically, we recorded bioimpedance artery pulse signals at a low sampling rate, reducing the data size and subsequently algorithmically reconstructing these signals at a higher sampling rate. We were able to retain vital transit time information and achieved enhanced precision that is comparable to the traditional high-rate sampling method. Our research demonstrates the viability of the algorithmic method for enabling PWV analysis from low-sampling-rate data, overcoming the constraints of conventional approaches. This technique has the potential to contribute to the development of cardiovascular health monitoring and diagnosis using closely spaced wearable devices for real-time and low-resource PWV assessment, enhancing patient care and cardiovascular disease management.

Optogenetic Targeting of Mouse Vagal Afferents Using an Organ-specific, Scalable, Wireless Optoelectronic Device.

Optogenetics has the potential to transform the study of the peripheral nervous system (PNS), but the complex anatomy of the PNS poses unique challenges for the focused delivery of light to specific tissues. This protocol describes the fabrication of a wireless telemetry system for studying peripheral sensory pathways. Unlike existing wireless approaches, the low-power wireless telemetry offers organ specificity via a sandwiched pre-curved tether, and enables high-throughput analysis of behavioral experiments with a channel isolation strategy. We describe the technical procedures for the construction of these devices, the wireless power transmission (TX) system with antenna coils, and their implementation for in vivo experimental applications. In total, the timeline of the procedure, including device fabrication, implantation, and preparation to begin in vivo experimentation can be completed in ~2-4 weeks. Implementation of these devices allows for chronic (>1 month) wireless optogenetic manipulation of peripheral neural pathways in freely behaving animals navigating homecage environments (up to 8).

AI-enabled, implantable, multichannel wireless telemetry for photodynamic therapy.

Photodynamic therapy (PDT) offers several advantages for treating cancers, but its efficacy is highly dependent on light delivery to activate a photosensitizer. Advances in wireless technologies enable remote delivery of light to tumors, but suffer from key limitations, including low levels of tissue penetration and photosensitizer activation. Here, we introduce DeepLabCut (DLC)-informed low-power wireless telemetry with an integrated thermal/light simulation platform that overcomes the above constraints. The simulator produces an optimized combination of wavelengths and light sources, and DLC-assisted wireless telemetry uses the parameters from the simulator to enable adequate illumination of tumors through high-throughput (<20 mice) and multi-wavelength operation. Together, they establish a range of guidelines for effective PDT regimen design. In vivo Hypericin and Foscan mediated PDT, using cancer xenograft models, demonstrates substantial suppression of tumor growth, warranting further investigation in research and/or clinical settings.

Robust, wireless gastric optogenetic implants for the study of peripheral pathways and applications in obesity.

Optogenetics has the potential to transform the study of organ functions in the peripheral nervous system via relatively easy access to the nerves and a direct link between the brain and organ systems. Implementation typically requires a static skeletal feature for the securement of a fiber. Unfortunately, the soft nature of peripheral nervous systems makes the wired fiber-optic approach less ideal for the study of the peripheral nervous system. Existing wireless approaches could bypass some constraints associated with optical fibers and thereby offer organ specificity. However, they suffer from durability loss due to considerable biological strains and unable to perform longitudinal experiments. Here, we propose a new class of wireless gastric optogenetic implant for identifying signaling pathways, in particular viscerosensory pathways, that can regulate food intake to treat obesity. Robust, wireless gastric optogenetic implants with a tubing-assisted U-shaped tether directly interface with nerve endings in the stomach with chronic stability in operation (> 100 kilocycles) and allows for optogenetic stimulations of vagus nerves in a freely behaving animal. We demonstrated utilities of the proposed wireless device in in vivo experiments. Results suggest the potential for identifying interventions for the treatment of obesity.Clinical Relevance - Identification of the roles of subpopulations in viscerosensory pathways would provide the platform for the development of better therapeutics for the treatment of obesity.

Multimodal Sensing Capabilities for the Detection of Shunt Failure.

Hydrocephalus is a medical condition characterized by the abnormal accumulation of cerebrospinal fluid (CSF) within the cavities of the brain called ventricles. It frequently follows pediatric and adult congenital malformations, stroke, meningitis, aneurysmal rupture, brain tumors, and traumatic brain injury. CSF diversion devices, or shunts, have become the primary therapy for hydrocephalus treatment for nearly 60 years. However, routine treatment complications associated with a shunt device are infection, obstruction, and over drainage. Although some (regrettably, the minority) patients with shunts can go for years without complications, even those lucky few may potentially experience one shunt malfunction; a shunt complication can require emergency intervention. Here, we present a soft, wireless device that monitors distal terminal fluid flow and transmits measurements to a smartphone via a low-power Bluetooth communication when requested. The proposed multimodal sensing device enabled by flow sensors, for measurements of flow rate and electrodes for measurements of resistance in a fluidic chamber, allows precision measurement of CSF flow rate over a long time and under any circumstances caused by unexpected or abnormal events. A universal design compatible with any modern commercial spinal fluid shunt system would enable the widespread use of this technology.

Organ-specific, multimodal, wireless optoelectronics for high-throughput phenotyping of peripheral neural pathways.

The vagus nerve supports diverse autonomic functions and behaviors important for health and survival. To understand how specific components of the vagus contribute to behaviors and long-term physiological effects, it is critical to modulate their activity with anatomical specificity in awake, freely behaving conditions using reliable methods. Here, we introduce an organ-specific scalable, multimodal, wireless optoelectronic device for precise and chronic optogenetic manipulations in vivo. When combined with an advanced, coil-antenna system and a multiplexing strategy for powering 8 individual homecages using a single RF transmitter, the proposed wireless telemetry enables low cost, high-throughput, and precise functional mapping of peripheral neural circuits, including long-term behavioral and physiological measurements. Deployment of these technologies reveals an unexpected role for stomach, non-stretch vagal sensory fibers in suppressing appetite and demonstrates the durability of the miniature wireless device inside harsh gastric conditions.

Fully Implantable Low-Power High Frequency Range Optoelectronic Devices for Dual-Channel Modulation in the Brain.

Wireless optoelectronic devices can deliver light to targeted regions in the brain and modulate discrete circuits in an animal that is awake. Here, we propose a miniaturized fully implantable low-power optoelectronic device that allows for advanced operational modes and the stimulation/inhibition of deep brain circuits in a freely-behaving animal. The combination of low power control logic circuits, including a reed switch and dual-coil wireless power transfer platform, provides powerful capabilities for the dissection of discrete brain circuits in wide spatial coverage for mouse activity. The actuating mechanism enabled by a reed switch results in a simplified, low-power wireless operation and systematic experimental studies that are required for a range of logical operating conditions. In this study, we suggest two different actuating mechanisms by (1) a magnet or (2) a radio-frequency signal that consumes only under 300 µA for switching or channel selection, which is a several ten-folds reduction in power consumption when compared with any other existing systems such as embedded microcontrollers, near field communication, and Bluetooth. With the efficient dual-coil transmission antenna, the proposed platform leads to more advantageous power budgets that offer improved volumetric and angular coverage in a cage while minimizing the secondary effects associated with a corresponding increase in transmitted power.