Imitating the respiratory activity of the brain stem by using artificial neural networks: exploratory study on an animal model of lactic acidosis and proof of concept.

Artificial neural networks (ANNs) are versatile tools capable of learning without prior knowledge. This study aims to evaluate whether ANN can calculate minute volume during spontaneous breathing after being trained using data from an animal model of metabolic acidosis. Data was collected from ten anesthetized, spontaneously breathing pigs divided randomly into two groups, one without dead space and the other with dead space at the beginning of the experiment. Each group underwent two equal sequences of pH lowering with pre-defined targets by continuous infusion of lactic acid. The inputs to ANNs were pH, ΔPaCO2 (variation of the arterial partial pressure of CO2), PaO2, and blood temperature which were sampled from the animal model. The output was the delta minute volume (ΔVM), (the change of minute volume as compared to the minute volume the animal had at the beginning of the experiment). The ANN performance was analyzed using mean squared error (MSE), linear regression, and the Bland-Altman (B-A) method. The animal experiment provided the necessary data to train the ANN. The best architecture of ANN had 17 intermediate neurons; the best performance of the finally trained ANN had a linear regression with R2 of 0.99, an MSE of 0.001 [L/min], a B-A analysis with bias ± standard deviation of 0.006 ± 0.039 [L/min]. ANNs can accurately estimate ΔVM using the same information that arrives at the respiratory centers. This performance makes them a promising component for the future development of closed-loop artificial ventilators.

Oxygen-Generating Scaffolds: One Step Closer to the Clinical Translation of Tissue Engineered Products.

The lack of oxygen supply in engineered constructs has been an ongoing challenge for tissue engineering and regenerative medicine. Upon implantation of an engineered tissue, spontaneous blood vessel formation does not happen rapidly, therefore, there is typically a limited availability of oxygen in engineered biomaterials. Providing oxygen in large tissue-engineered constructs is a major challenge that hinders the development of clinically relevant engineered tissues. Similarly, maintaining adequate oxygen levels in cell-laden tissue engineered products during transportation and storage is another hurdle. There is an unmet demand for functional scaffolds that could actively produce and deliver oxygen, attainable by incorporating oxygen-generating materials. Recent approaches include encapsulation of oxygen-generating agents such as solid peroxides, liquid peroxides, and fluorinated substances in the scaffolds. Recent approaches to mitigate the adverse effects, as well as achieving a sustained and controlled release of oxygen, are discussed. Importance of oxygen-generating materials in various tissue engineering approaches such as ex vivo tissue engineering, in situ tissue engineering, and bioprinting are highlighted in detail. In addition, the existing challenges, possible solutions, and future strategies that aim to design clinically relevant multifunctional oxygen-generating biomaterials are provided in this review paper.

Transmission-Based Vertebrae Strength Probe Development: Far Field Probe Property Extraction and Integrated Machine Vision Distance Validation Experiments.

We are developing a transmission-based probe for point-of-care assessment of vertebrae strength needed for fabricating the instrumentation used in supporting the spinal column during spinal fusion surgery. The device is based on a transmission probe whereby thin coaxial probes are inserted into the small canals through the pedicles and into the vertebrae, and a broad band signal is transmitted from one probe to the other across the bone tissue. Simultaneously, a machine vision scheme has been developed to measure the separation distance between the probe tips while they are inserted into the vertebrae. The latter technique includes a small camera mounted to the handle of one probe and associated fiducials printed on the other. Machine vision techniques make it possible to track the location of the fiducial-based probe tip and compare it to the fixed coordinate location of the camera-based probe tip. The combination of the two methods allows for straightforward calculation of tissue characteristics by exploiting the antenna far field approximation. Validation tests of the two concepts are presented as a precursor to clinical prototype development.

Open-Ended Transmission Coaxial Probes for Sarcopenia Assessment.

We developed a handheld, side-by-side transmission-based probe for interrogating tissue to diagnose sarcopenia-a condition largely characterized by muscle loss and replacement by fat. While commercial microwave reflection-based probes exist, they can only be used in a lab for a variety of applications. The penetration depth of these probes is only in the order of 0.3 mm, which does not even traverse the skin layer, and minor motion of the coaxial feedlines can completely dismantle the calibration. Our device builds primarily on the transmission-based concept that allows for substantially greater signal penetration depth operating over a very broad bandwidth. Additional features were integrated to further improve the penetration, optimize the geometry for a more focused planar excitation, and juxtapose the coaxial apertures for more controlled interrogation. The larger coaxial apertures further increased the penetration depth while retaining the broadband performance. Three-dimensional printing technology made it possible for the apertures to be compressed into ellipses for interrogation in a near-planar geometry. Finally, fixed side-by-side positioning provided repeatable and reliable performance. The probes were also not susceptible to multipath signal corruption due to the close proximity of the transmitting and receiving apertures. The new concept worked from 100 MHz to over 8 GHz and could sense property changes as deep as 2-3 cm. While the signal changes due to deeper feature aberrations were more subtle than for signals emanating from the skin and subcutaneous fat layers, the large property contrast between muscle and fat is a sarcopenic indication that helps to distinguish even the deepest objects. This device has the potential to provide needed specificity information about the relevant underlying tissue.

QRS dispersion detected in ARVC patients and healthy gene carriers using 252-leads body surface mapping: an explorative study of a potential diagnostic tool for arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: The diagnosis of ARVC remains complex requiring both imaging and electrocardiographic (ECG) techniques. The purpose was therefore to investigate whether QRS dispersion assessed by body surface mapping (BSM) could be used to detect early signs of ARVC, particularly in gene carriers. METHODS: ARVC patients, gene carriers without a history of arrhythmias or structural cardiac changes and healthy controls underwent 12-lead resting ECG, signal-averaged ECG, echocardiographic examination, 24-hours Holter monitoring, and BSM with electrocardiographic imaging. All 252-leads BSM recordings and 12-leads ECG recordings were manually analyzed for QRS durations and QRS dispersion. RESULTS: Eight controls, 12 ARVC patients with definite ARVC and 20 healthy gene carriers were included. The ECG-QRS dispersion was significantly greater in ARVC patients (42 vs. 25 ms, p < .05), but failed to fully differentiate them from controls. The BSM-derived QRS dispersion was also significantly greater in ARVC patients versus controls (65 vs. 29 ms, p < .05) and distinguished 11/12 cases from controls using the cut-off 40msec. The BSM derived QRS dispersion was abnormal (> 40 ms) in 4/20 healthy gene carriers without signs of ARVC, which may indicate early depolarization changes. CONCLUSIONS: QRS dispersion, when assessed by BSM versus 12-lead ECG, seem to better distinguish ARVC patients from controls, and could potentially be used to detect early ARVC in gene carriers. Further studies are required to confirm the value of BSM-QRS dispersion in this respect.

Design of Metamaterial Based Efficient Wireless Power Transfer System Utilizing Antenna Topology for Wearable Devices.

In this article, the design of an efficient wireless power transfer (WPT) system using antenna-based topology for the applications in wearable devices is presented. To implement the wearable WPT system, a simple circular patch antenna is initially designed on a flexible felt substrate by placing over a three-layer human tissue model to utilize as a receiving element. Meanwhile, a high gain circular patch antenna is also designed in the air environment to use as a transmitter for designing the wearable WPT link. The proposed WPT system is built to operate at the industrial, scientific and medical (ISM) band of 2.40-2.48 GHz. In addition, to improve the power transfer efficiency (PTE) of the system, a metamaterial (MTM) slab built with an array combination of 3 × 3 unit cells has been employed. Further, the performance analysis of the MTM integrated system is performed on the different portions of the human body like hand, head and torso model to present the versatile applicability of the system. Moreover, analysis of the specific absorption rate (SAR) has been performed in different wearable scenarios to show the effect on the human body under the standard recommended limits. Regarding the practical application issues, the performance stability analysis of the proposed system due to the misalignment and flexibility of the Rx antenna is executed. Finally, the prototypes are fabricated and experimental validation is performed on several realistic wearable platforms like three-layer pork tissue slab, human hand, head and body. The simulated and measured result confirms that by using the MTM slab, a significant amount of the PTE improvement is obtained from the proposed system.

MAS: Standalone Microwave Resonator to Assess Muscle Quality.

Microwave-based sensing for tissue analysis is recently gaining interest due to advantages such as non-ionizing radiation and non-invasiveness. We have developed a set of transmission sensors for microwave-based real-time sensing to quantify muscle mass and quality. In connection, we verified the sensors by 3D simulations, tested them in a laboratory on a homogeneous three-layer tissue model, and collected pilot clinical data in 20 patients and 25 healthy volunteers. This report focuses on initial sensor designs for the Muscle Analyzer System (MAS), their simulation, laboratory trials and clinical trials followed by developing three new sensors and their performance comparison. In the clinical studies, correlation studies were done to compare MAS performance with other clinical standards, specifically the skeletal muscle index, for muscle mass quantification. The results showed limited signal penetration depth for the Split Ring Resonator (SRR) sensor. New sensors were designed incorporating Substrate Integrated Waveguides (SIW) and a bandstop filter to overcome this problem. The sensors were validated through 3D simulations in which they showed increased penetration depth through tissue when compared to the SRR. The second-generation sensors offer higher penetration depth which will improve clinical data collection and validation. The bandstop filter is fabricated and studied in a group of volunteers, showing more reliable data that warrants further continuation of this development.

Gelatin-methacryloyl hydrogel based in vitro blood-brain barrier model for studying breast cancer-associated brain metastasis.

Breast cancer is one of the leading causes of brain metastasis. Metastasis to the brain occurs if cancer cells manage to traverse the 'blood-brain barrier' (BBB), which is a barrier with a very tight junction (TJ) of endothelial cells between blood circulation and brain tissue. It is highly important to develop novel in vitro BBB models to investigate breast cancer metastasis to the brain to facilitate the screening of chemotherapeutic agents against it. We herein report the development of gelatin methacryloyl (GelMA) modified transwell insert based BBB model composed of endothelial and astrocyte cell layers for testing the efficacy of anti-metastatic agents against breast cancer metastasis to the brain. We characterized the developed model for the morphology and in vitro breast cancer cell migration. Furthermore, we investigated the effect of cisplatin, a widely used chemotherapeutic agent, on the migration of metastatic breast cancer cells using the model. Our results showed that breast cancer cells migrate across the developed BBB model. Cisplatin treatment inhibited the migration of cancer cells across the model. Findings of this study suggest that our BBB model can be used as a suitable tool to investigate breast cancer-associated brain metastasis and to identify suitable therapeutic agents against this.

Development of titanium dioxide nanowire incorporated poly(vinylidene fluoride-trifluoroethylene) scaffolds for bone tissue engineering applications.

Critical size bone defects that do not heal spontaneously are among the major reasons for the disability in majority of people with locomotor disabilities. Tissue engineering has become a promising approach for repairing such large tissue injuries including critical size bone defects. Three-dimension (3D) porous scaffolds based on piezoelectric polymers like poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) have received a lot of attention in bone tissue engineering due to their favorable osteogenic properties. Owing to the favourable redox properties, titanium dioxide (TiO2) nanostructures have gained a great deal of attention in bone tissue engineering. In this paper, tissue engineering scaffolds based on P(VDF-TrFE) loaded with TiO2 nanowires (TNW) were developed and evaluated for bone tissue engineering. Wet-chemical method was used for the synthesis of TNW. Obtained TNW were thoroughly characterized for the physicochemical and morphological properties using techniques such as X-Ray diffraction (XRD) analysis and transmission electron microscopy (TEM). Electrospinning was used to produce TNW incorporated P(VDF-TrFE) scaffolds. Developed scaffolds were characterized by state of art techniques such as Scanning Electron Microscopy (SEM), XRD and Differential scanning calorimetry (DSC) analyses. TEM analysis revealed that the obtained TiO2 nanostructures possess nanofibrous morphology with an average diameter of 26 ± 4 nm. Results of characterization of nanocomposite scaffolds confirmed the effective loading of TNW in P(VDF-TrFE) matrix. Fabricated P(VDF-TrFE)/TNW scaffolds possessed good mechanical strength and cytocompatibility. Osteoblast like cells showed higher adhesion and proliferation on the nanocomposite scaffolds. This investigation revealed that the developed P(VDF-TrFE) scaffolds containing TNW can be used as potential scaffolds for bone tissue engineering applications.

Electrospun polyvinyl alcohol membranes incorporated with green synthesized silver nanoparticles for wound dressing applications.

Electrospun membranes have the potential to act as an effective barrier for wounds from the external environment to prevent pathogens. In addition, materials with good antibacterial properties can effectively fight off the invading pathogens. In this paper, we report the development of a novel electrospun polyvinyl alcohol (PVA) membrane containing biosynthesized silver nanoparticle (bAg) for wound dressing applications. Plant extract from a medicinal plant Mimosa pudica was utilized for the synthesis of bAg. Synthesized bAg were characterized by Ultraviolet-Visible (UV) Spectroscopy and Fourier Transform Infrared Spectroscopy (FTIR). The morphology of bAg was obtained from Transmission Electron Microscopy (TEM) and found that they were spherical in morphology with average particle size 7.63 ± 1.2 nm. bAg nanoparticles incorporated PVA membranes were characterized using several physicochemical techniques such as Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDS) and X-Ray Diffraction (XRD) analysis. Experimental results confirmed the successful incorporation of bAg in PVA fibers. PVA nanofiber membranes incorporated with bAg showed good mechanical strength, excellent exudate uptake capacity, antibacterial activity, blood compatibility and cytocompatibility.

Characterization of the Fat Channel for Intra-Body Communication at R-Band Frequencies.

In this paper, we investigate the use of fat tissue as a communication channel between in-body, implanted devices at R-band frequencies (1.7⁻2.6 GHz). The proposed fat channel is based on an anatomical model of the human body. We propose a novel probe that is optimized to efficiently radiate the R-band frequencies into the fat tissue. We use our probe to evaluate the path loss of the fat channel by studying the channel transmission coefficient over the R-band frequencies. We conduct extensive simulation studies and validate our results by experimentation on phantom and ex-vivo porcine tissue, with good agreement between simulations and experiments. We demonstrate a performance comparison between the fat channel and similar waveguide structures. Our characterization of the fat channel reveals propagation path loss of ∼0.7 dB and ∼1.9 dB per cm for phantom and ex-vivo porcine tissue, respectively. These results demonstrate that fat tissue can be used as a communication channel for high data rate intra-body networks.

Split-Ring Resonator Sensor Penetration Depth Assessment Using In Vivo Microwave Reflectivity and Ultrasound Measurements for Lower Extremity Trauma Rehabilitation.

In recent research, microwave sensors have been used to follow up the recovery of lower extremity trauma patients. This is done mainly by monitoring the changes of dielectric properties of lower limb tissues such as skin, fat, muscle, and bone. As part of the characterization of the microwave sensor, it is crucial to assess the signal penetration in in vivo tissues. This work presents a new approach for investigating the penetration depth of planar microwave sensors based on the Split-Ring Resonator in the in vivo context of the femoral area. This approach is based on the optimization of a 3D simulation model using the platform of CST Microwave Studio and consisting of a sensor of the considered type and a multilayered material representing the femoral area. The geometry of the layered material is built based on information from ultrasound images and includes mainly the thicknesses of skin, fat, and muscle tissues. The optimization target is the measured S11 parameters at the sensor connector and the fitting parameters are the permittivity of each layer of the material. Four positions in the femoral area (two at distal and two at thigh) in four volunteers are considered for the in vivo study. The penetration depths are finally calculated with the help of the electric field distribution in simulations of the optimized model for each one of the 16 considered positions. The numerical results show that positions at the thigh contribute the highest penetration values of up to 17.5 mm. This finding has a high significance in planning in vitro penetration depth measurements and other tests that are going to be performed in the future.

Technical Aspects and Validation of a New Biofeedback System for Measuring Lower Limb Loading in the Dynamic Situation.

BACKGROUND: A variety of techniques for measuring lower limb loading exists, each with their own limitations. A new ambulatory biofeedback system was developed to overcome these limitations. In this study, we described the technical aspects and validated the accuracy of this system. METHODS: A bench press was used to validate the system in the static situation. Ten healthy volunteers were measured by the new biofeedback system and a dual-belt instrumented treadmill to validate the system in the dynamic situation. RESULTS: Bench press results showed that the sensor accurately measured peak loads up to 1000 N in the static situation. In the healthy volunteers, the load curves measured by the biofeedback system were similar to the treadmill. However, the peak loads and loading rates were lower in the biofeedback system in all participants at all speeds. CONCLUSIONS: Advanced sensor technologies used in the new biofeedback system resulted in highly accurate measurements in the static situation. The position of the sensor and the design of the biofeedback system should be optimized to improve results in the dynamic situation.

Microwave Vertebrae Strength Probe Development: Robust and Fast Phase Unwrapping Technique.

We have developed a new transmission-based, open-ended coaxial probe for assessing vertebrae strength during spinal fusion surgery. The approach exploits the fact that the probes are within the far field of each other implying that the phase varies linearly with respect to propagation distance. Determining the absolute phase is critical for recovering the associated tissue dielectric properties from which bone strength will be determined. Unfortunately, unwanted multi-path signals corrupt the signals at the lower end of the operating frequency range from which our conventional unwrapping strategy depends. Our new approach requires only three measurements within the prime frequency range and can be determined robustly with a minimum of computations. This will be vital to developing a commercial device since the signal levels will be extremely low power requiring longer than usual data acquisition times, which will be mitigated by measuring the data at only a few frequencies. Fast and efficient operation will be critical for clinical success.

Histopathology-driven prostate cancer identification: A VBIR approach with CLAHE and GLCM insights.

Efficient extraction and analysis of histopathological images are crucial for accurate medical diagnoses, particularly for prostate cancer. This research enhances histopathological image reclamation by integrating Visual-Based Image Reclamation (VBIR) techniques with contrast-limited adaptive Histogram Equalization (CLAHE) and the Gray-Level Co-occurrence Matrix (GLCM) algorithm. The proposed method leverages CLAHE to improve image contrast and visibility, crucial for regions with varying illumination, and employs a non-linear Support Vector Machine (SVM) to incorporate GLCM features. Our approach achieved a notable success rate of 89.6%, demonstrating significant improvement in image analysis. The average execution time for matched tissues was 41.23 s (standard deviation 36.87 s), and for unmatched tissues, 21.22 s (standard deviation 29.18 s). These results underscore the method's efficiency and reliability in processing histopathological images. The findings from this study highlight the potential of our method to enhance image reclamation processes, paving the way for further research and advancements in medical image analysis. The superior performance of our approach signifies its capability to significantly improve histopathological image analysis, contributing to more accurate and efficient diagnostic practices.

Rotation insensitive implantable wireless power transfer system for medical devices using metamaterial-polarization converter.

This article introduces an innovative approach for creating a circular polarization (CP) antenna-based rotation-insensitive implantable wireless power transfer (WPT) system for medical devices. The system is constructed to work in the industrial, scientific, and medical (ISM) frequency band of 902-928 MHz. Initially, a flexible, wide-band, and bio-compatible open-ended CP slot antenna is designed within a single-layer human skin tissue model to serve as the receiving (Rx) element. To form the implantable WPT link, a circular patch antenna is also constructed in the free-space to use as a transmitting (Tx) source. Further, a new metamaterial-polarization converter (MTM-PC) structure is developed and incorporated into the proposed system to enhance the power transfer efficiency (PTE). Furthermore, the rotational phenomenon of the Rx implant has been studied to show how the rotation affects the system's performance. Moreover, a numerical analysis of the specific absorption rate (SAR) is conducted to confirm compliance with safety regulations and prioritize human safety from electromagnetic exposure. Finally, to validate the introduced concept, prototypes of the different elements of the proposed WPT system were fabricated and tested using skin-mimicking gel and porcine tissue. The measured results confirm the feasibility of the introduced approach, exhibiting improved efficiency due to use of the MTM-PC. The amplitude of the transmission coefficient ( | S 21 | ) has improved by 6.94 dB in the simulation, whereas the enhancement of 7.04 dB and 6.76 dB is obtained from the experimental study due to the integration of MTM-PC. As a result, the PTE of the proposed MTM-PC integrated implantable WPT system is increased significantly compared to the system without MTM-PC.

92 Mb/s Fat-Intrabody Communication (Fat-IBC) With Low-Cost WLAN Hardware.

The human subcutaneous fat layer, skin and muscle together act as a waveguide for microwave transmissions and provide a low-loss communication medium for implantable and wearable body area networks (BAN). In this work, fat-intrabody communication (Fat-IBC) as a human body-centric wireless communication link is explored. To reach a target 64 Mb/s inbody communication, wireless LAN in the 2.4 GHz band was tested using low-cost Raspberry Pi single-board computers. The link was characterized using scattering parameters, bit error rate (BER) for different modulation schemes, and IEEE 802.11n wireless communication using inbody (implanted) and onbody (on the skin) antenna combinations. The human body was emulated by phantoms of different lengths. All measurements were done in a shielded chamber to isolate the phantoms from external interference and to suppress unwanted transmission paths. The BER measurements show that, except when using dual on-body antennas with longer phantoms, the Fat-IBC link is very linear and can handle modulations as complex as 512-QAM without any significant degradation of the BER. For all antenna combinations and phantoms lengths, link speeds of 92 Mb/s were achieved using 40 MHz bandwidth provided by the IEEE 802.11n standard in the 2.4 GHz band. This speed is most likely limited by the used radio circuits, not the Fat-IBC link. The results show that Fat-IBC, using low-cost off-the-shelf hardware and established IEEE 802.11 wireless communication, can achieve high-speed data communication within the body. The obtained data rate is among the fastest measured with intrabody communication.

Stem Cells in Bone Tissue Engineering: Progress, Promises and Challenges.

Bone defects from accidents, congenital conditions, and age-related diseases significantly impact quality of life. Recent advancements in bone tissue engineering (TE) involve biomaterial scaffolds, patient-derived cells, and bioactive agents, enabling functional bone regeneration. Stem cells, obtained from numerous sources including umbilical cord blood, adipose tissue, bone marrow, and dental pulp, hold immense potential in bone TE. Induced pluripotent stem cells and genetically modified stem cells can also be used. Proper manipulation of physical, chemical, and biological stimulation is crucial for their proliferation, maintenance, and differentiation. Stem cells contribute to osteogenesis, osteoinduction, angiogenesis, and mineralization, essential for bone regeneration. This review provides an overview of the latest developments in stem cell-based TE for repairing and regenerating defective bones.

Scaffolds with high oxygen content support osteogenic cell survival under hypoxia.

Regeneration of large bone defects is a significant clinical challenge with variable success, but tissue engineering strategies are promising for rapid and effective bone regeneration. Maintaining an adequate oxygen level within implanted scaffolds is a major obstacle in bone tissue engineering. We developed a new oxygen-generating scaffold by electrospinning polycaprolactone with calcium peroxide (CaO2) nanocuboids (CPNCs) and characterized the physical, chemical, and biological properties of the resulting composites. Our scaffolds are highly porous and composed of submicron fibers that include CPNC as confirmed with XRD and FTIR analyses. Scaffolds containing CPNC provided controlled oxygen release for 14-days and supported cell proliferation while protecting preosteoblasts from hypoxia-induced cell death. Oxygen-generating scaffolds also facilitated bone mimetic defect contraction in vitro. The results suggest that our approach can be used to develop tissue-engineered products which target bone defects.

Harnessing the potential of oxygen-generating materials and their utilization in organ-specific delivery of oxygen.

The limited availability of transplantable organs hinders the success of patient treatment through organ transplantation. In addition, there are challenges with immune rejection and the risk of disease transmission when receiving organs from other individuals. Tissue engineering aims to overcome these challenges by generating functional three-dimensional (3D) tissue constructs. When developing tissues or organs of a particular shape, structure, and size as determined by the specific needs of the therapeutic intervention, a tissue specific oxygen supply to all parts of the tissue construct is an utmost requirement. Moreover, the lack of a functional vasculature in engineered tissues decreases cell survival upon implantation in the body. Oxygen-generating materials can alleviate this challenge in engineered tissue constructs by providing oxygen in a sustained and controlled manner. Oxygen-generating materials can be incorporated into 3D scaffolds allowing the cells to receive and utilize oxygen efficiently. In this review, we present an overview of the use of oxygen-generating materials in various tissue engineering applications in an organ specific manner as well as their potential use in the clinic.