Value of sonoelastography for diagnosis of breast non-mass lesions and comparison with BI-RADS: A systematic review and meta-analysis.

BACKGROUND: Not all the breast lesions were mass-like, some were non-mass-like at ultrasonography. In these lesions, conventional ultrasonography had a high sensitivity but a low specificity. Sonoelastography can evaluate tissue stiffness to differentiate malignant masses from benign ones. Then what about the non-mass lesions? The aim of this study was to evaluate the current accuracy of sonoelastography in the breast non-mass lesions and compare the results with those of the American College of Radiology breast Imaging-Reporting and Data System (BI-RADS). METHODS: An independent literature search of English medical databases, including PubMed, Web of Science, Embase & MEDLINE (Embase.com) and Cochrane Library, was performed by 2 researchers. The accuracy of sonoelastography was calculated and compared with those of BI-RADS. RESULTS: Fourteen relevant studies including 1058 breast non-mass lesions were included. Sonoelastography showed a pooled sensitivity of 0.74 (95% CI: 0.70-0.78), specificity of 0.89 (95% CI: 0.85-0.91), diagnostic odds ratio (DOR) of 25.22 (95% CI: 17.71-35.92), and an area under the curve of 0.9042. Eight articles included both sonoelastography and BI-RADS. The pooled sensitivity, specificity, DOR and AUC were 0.69 versus 0.91 (P < .01), 0.90 versus 0.68 (P < .01), 19.65 versus 29.34 (P > .05), and 0.8685 versus 0.9327 (P > .05), respectively. CONCLUSIONS: Sonoelastography has a higher specificity and a lower sensitivity for differential diagnosis between malignant and benign breast non-mass lesions compared with BI-RADS, although there were no differences in AUC between them.

Comparison of artificial intelligence, elastic imaging, and the thyroid imaging reporting and data system in the differential diagnosis of suspicious nodules.

Background: Ultrasound is widely used for detecting thyroid nodules in clinical practice. This retrospective study aimed to assess the diagnostic efficacy of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS), S-Detect, and elastography of the carotid artery for suspicious thyroid nodules and to determine the complementary value of artificial intelligence and elastography. Methods: Between January 2021 and November 2021, 101 consecutive patients with 138 thyroid nodules were enrolled in The First Hospital of China Medical University. All nodules were evaluated using ACR-TIRADS categories (TR), S-Detect, and elastography, and then the diagnostic performance of the different methods and the combined assessment were compared. The inclusion criteria were the following: (I) TR3, TR4, and TR5 nodules, which were defined as "suspicious nodules"; (II) patients who had surgical or cytopathological results after ultrasound examination; and (III) voluntary enrollment in this study. Meanwhile, the exclusion criteria were the following: (I) TR1 and TR2 nodules, (II) patients who had undergone fine-needle aspiration before ultrasound examination, and (III) inconclusive cytologic findings. Results: A total of 71 patients (12 men and 59 women) with 94 suspicious thyroid nodules (42 benign nodules and 52 malignant nodules) were finally included in this study. S-Detect had a significantly better sensitivity than did ACR-TIRADS [S-Detect: 98.1%, 95% confidence interval (CI): 89.7-100.0%; ACR-TIRADS: 84.6%, 95% CI: 71.9-93.1%; P=0.036], but its specificity was much lower (S-Detect: 19.0%; 95% CI: 8.6-34.1%; ACR-TIRADS: 40.5%, 95% CI: 25.6-56.7%; P=0.032). The accuracy was not significantly different between S-Detect (62.8%; 95% CI: 52.2-72.5%) and ACR-TIRADS (64.9%; 95% CI: 54.4-74.5%) (P=0.761). The elasticity contrast index (ECI) was not definitively useful in identifying suspicious thyroid nodules (P=0.592). Compared with the use of ACR-TIRADS and S-Detect alone, the specificity (45.2%; 95% CI: 29.8-61.3%), positive predictive value (65.2%; 95% CI: 52.4-76.5%), accuracy (66.0%; 95% CI: 55.5-75.4%), and the area under the receiver operating characteristic curve (0.640; 95% CI: 0.534-0.736) of their combination were higher but not significantly so. Conclusions: At present, S-Detect cannot replace manual diagnosis, and the value of elastography of the carotid artery in diagnosing suspected thyroid nodules remains unclear.

Electroacupuncture Zusanli (ST36) Relieves Somatic Pain in Colitis Rats by Inhibiting Dorsal Root Ganglion Sympathetic-Sensory Coupling and Neurogenic Inflammation.

Referred somatic pain triggered by hyperalgesia is common in patients with inflammatory bowel disease (IBD). It was reported that sprouting of sympathetic nerve fibers into the dorsal root ganglion (DGR) and neurogenic inflammation were related to neuropathic pain, the excitability of neurons, and afferents. The purpose of the study was to explore the potential and mechanism of electroacupuncture (EA) at Zusanli (ST36) for the intervention of colon inflammation and hyperalgesia. Sprague-Dawley (SD) was randomly divided into four groups, including control, model, EA, and sham-EA. Our results showed EA treatment significantly attenuated dextran sulfate sodium- (DSS-) induced colorectal lesions and inflammatory cytokine secretion, such as TNF-α, IL-1ß, PGE2, and IL-6. EA also inhibited mechanical and thermal pain hypersensitivities of colitis rats. Importantly, EA effectively abrogated the promotion effect of DSS on ipsilateral lumbar 6 (L6) DRG sympathetic-sensory coupling, manifested as the sprouting of tyrosine hydroxylase- (TH-) positive sympathetic fibers into sensory neurons and colocalization of and calcitonin gene-related peptide (CGRP). Furthermore, EA at Zusanli (ST36) activated neurogenic inflammation, characterized by decreased expression of substance P (SP), hyaluronic acid (HA), bradykinin (BK), and prostacyclin (PGI2) in colitis rat skin tissues corresponding to the L6 DRG. Mechanically, EA treatment reduced the activation of the TRPV1/CGRP, ERK, and TLR4 signaling pathways in L6 DRG of colitis rats. Taken together, we presumed that EA treatment improved colon inflammation and hyperalgesia, potentially by suppressing the sprouting of sympathetic nerve fibers into the L6 DGR and neurogenic inflammation via deactivating the TRPV1/CGRP, ERK, and TLR4 signaling pathways.

Evaluation of Enzyme Inhibitory Activity of Flavonoids by Polydopamine-Modified Hollow Fiber-Immobilized Xanthine Oxidase.

In this study, a polydopamine (PDA)-modified hollow fiber-immobilized xanthine oxidase (XOD) was prepared for screening potential XOD inhibitors from flavonoids. Several parameters for the preparation of PDA-modified hollow fiber-immobilized XOD, including the dopamine concentration, modification time, XOD concentration and immobilization time, were optimized. The results show that the optimal conditions for immobilized XOD activity were a dopamine concentration of 2.0 mg/mL in 10.0 mM Tris-HCl buffer (pH 8.5), a modification time of 3.0 h, an XOD concentration of 1000 µg/mL in 10.0 mM phosphate buffer (pH 7.5) and an immobilization time of 3.0 h. Subsequently, the enzymatic reaction conditions such as the pH value and temperature were investigated, and the enzyme kinetics and inhibition parameters were determined. The results indicate that the optimal pH value (7.5) and temperature (37 °C) of the PDA-modified hollow fiber-immobilized XOD were consistent with the free enzyme. Moreover, the PDA-modified hollow fiber-immobilized XOD could still maintain above 50% of its initial immobilized enzyme activity after seven consecutive cycles. The Michaelis-Menten constant (Km) and the half-maximal inhibitory concentration (IC50) of allopurinol on the immobilized XOD were determined as 0.25 mM and 23.2 µM, respectively. Furthermore, the PDA-modified hollow fiber-immobilized XOD was successfully applied to evaluate the inhibitory activity of eight flavonoids. Quercetin, apigenin, puerarin and epigallocatechin showed a good inhibition effect, and their percentages of inhibition were (79.86 ± 3.50)%, (80.98 ± 0.64)%, (61.15 ± 6.26)% and (54.92 ± 0.41)%, respectively. Finally, molecular docking analysis further verified that these four active compounds could bind to the amino acid residues in the XOD active site. In summary, the PDA-modified hollow fiber-immobilized XOD is an efficient method for the primary screening of XOD inhibitors from natural products.

Preparation of a zirconium terephthalate metal-organic framework coated magnetic nanoparticle for the extraction of berberine prior to high-performance liquid chromatography analysis.

In this study, a zirconium terephthalate metal-organic framework-coated magnetic nanoparticle (UiO-66@PA@PEI@Fe3 O4 ) was synthesized for the extraction of berberine prior to high-performance liquid chromatography analysis. The phytic acid, which could be grafted onto the magnetic nanoparticle through electrostatic interaction with the abundant amino groups of polyethylenimine, possesses outstanding metal ion coordination ability for the immobilization of metal-organic frameworks UiO-66. The physicochemical properties of the obtained nanoparticle were thoroughly investigated by a series of characterization techniques. Then, the factors that will affect the extraction efficiency and recovery of berberine were investigated. Results indicated that the material had good stability and reusability, and high adsorption capacity (50.01 mg/g) to berberine through single-layer adsorption. In addition, a molecular docking study indicated that the interactions between the material and berberine were mainly π-π stacking and hydrophobic interaction. Finally, the material was successfully applied to the extraction of berberine in Rhizoma Coptidis and Cortex Phellodendri extracts with the recoveries of 76.1% and 71.6%, respectively.

Adsorbed hollow fiber immobilized tyrosinase for the screening of enzyme inhibitors from Pueraria lobata extract.

In this study, a method based on adsorbed hollow fiber immobilized tyrosinase (TYR) was developed to screening potential TYR inhibitors from Pueraria lobate extract. Kojic acid and ranitidine were used as positive and negative control to verify the reliability of the proposed method, respectively. Several significant parameters of the screening process, including the amount of P. lobata extract, adsorption time and incubation time, were optimized. After investigating the repeatability of the developed method, seven potential active compounds in P. lobata extract were successfully detected and their chemical structures were tentatively identified by liquid chromatography - mass spectrometry analysis. Furthermore, the inhibitory activity of four identified compounds on TYR was tested in vitro, and three of them, namely, puerarin, puerarin-6″-O-xyloside and puerarin apioside were verified to have good TYR inhibitory activity with IC50 value of 478.5, 513.8, and 877.3 µM, respectively. In addition, the molecular docking results indicated that these compounds could bind to the amino acid residues in TYR catalytic pocket. These results proved that the proposed method is a feasible approach for screening of TYR inhibitors from plant extract.

Antithrombotic effect and action mechanism of Salvia miltiorrhiza and Panax notoginseng herbal pair on the zebrafish.

BACKGROUND: Salvia miltiorrhiza (Danshen, DS) and Panax notoginseng (Sanqi, SQ) are famous traditional Chinese herbs, and their herbal pair (DS-SQ) has been popular used as anti-thrombotic medicines. However, there is still a lack of sufficient scientific evidence to illustrate the optimum combination ratio of these two herbs as well as its action mechanisms. The purpose of this study is to investigate the anti-thrombotic effects of DS-SQ on zebrafish and explore its possible action mechanism. METHODS: Firstly, the chemical components in DS-SQ extract were analyzed by LC-ESI-MS/MS. Then, a phenylhydrazine (PHZ)-induced zebrafish thrombosis model was developed for evaluating the anti-thrombotic effects of DS-SQ extracts with different combination ratios and their nine pure compounds. Followed, Real-time quantitative PCR (RT-qPCR) assays were performed to investigate the potential antithrombotic mechanisms of DS-SQ. RESULTS: Thirty-three components were tentatively identified by LC-MS analysis. DS-SQ at the ratio of 10:1 presented the best anti-thrombotic effect, and rosmarinic acid, lithospermic acid and salvianolic acid B of DS showed good anti-thrombotic activity on zebrafish thrombosis model. The RT-qPCR assays indicated that DS-SQ (10:1) could cure the PHZ-induced thrombosis by downregulating the expression of PKCα, PKCß, fga, fgb, fgg and vWF in zebrafish. CONCLUSIONS: DS-SQ with the combination ratio of 10:1 showed optimum anti-thrombotic effect on PHZ-induced zebrafish thrombosis model, which provided a reference for reasonable clinical applications of DS-SQ herbal pair.

Controlling Nutritional Status (CONUT) Score as a New Indicator of Prognosis in Patients With Hilar Cholangiocarcinoma Is Superior to NLR and PNI: A Single-Center Retrospective Study.

BACKGROUND: Currently, many nutritional indicators, including controlling nutritional status score (CONUT), can be used to assess a patient's nutritional status and have been reported as reliable predictors of multiple malignancies. However, the value of CONUT score in predicting postoperative outcomes in patients with hilar cholangiocarcinoma has not been explored. In this study, its predictive value will be discussed and compared with the known predictors the neutrophil lymphocyte ratio (NLR) and prognostic nutritional index (PNI). METHODS: Preoperative CONUT scores, PNI and NLR levels of 94 Hilar cholangiocarcinoma (HCCA) patients who underwent radical-intent resection of hepatobiliary surgery in our hospital from March 2010 to April 2019 were retrospectively collected and analyzed. They were grouped according to their optimal cutoff value and the prognostic effects of patients in each group were compared respectively. RESULTS: CONUThigh was more frequent in patients with Clavien-Dindo classification of ≥IIIa (P = 0.008) and Bile leakage presence (P = 0.011). Kaplan-Meier curves analyzing the relationship between CONUT, PNI, and NLR values and HCCA patient survival (including total survival (OS) and recurrence-free survival (RFS) showed significant differences between groups (P <0.001). Meanwhile, multi-factor analysis found that Degree of cure, PNI, NLR, and preoperative CONUT score were independent prognostic factors for OS and RFS. The predictive power of CONUT score was higher than that of NLR and PNI based on time-dependent receiver operating Characteristic (ROC) analysis and the net reclassification index (NRI) and integrated discriminatory index (IDI) values (P < 0.05). CONCLUSION: CONUT score may be of some clinical reference value in evaluating postoperative prognosis of HCCA patients.

Expression of Smo in pancreatic cancer CD44+CD24+cells and construction of a lentiviral expression vector to silence Smo.

The present study focused on the roles of members of the Hedgehog (Hh) signaling pathway in the maintenance of malignant biological characteristics, such as tumorigenesis, similar to that of pancreatic tumor cells. Cluster of differentiation (CD)44+CD24+/CD44-CD24- cells were isolated from three different pancreatic cancer cell lines by flow cytometry. Among the three pancreatic cancer cell lines, the SW1990 cell line exhibited the highest percentage of CD44+CD24+ cells, which accounted for 39.9% of the total. The expression of members of the Hh signaling pathway in CD44+CD24+/CD44-CD24- cells was detected using reverse transcription-polymerase chain reaction and western blot analysis. The results demonstrated that members of the Hh signaling pathway were differentially expressed in CD44+CD24+ cells compared with CD44-CD24-, normal pancreatic duct cells and unsorted SW1990 cells. In addition, lentiviral expression vectors expressing Smoothened (Smo) small interfering RNA (siRNA) were constructed. Following transfection with the lentiviral expression vectors, Smo expression was markedly reduced in CD44+CD24+ cells. The present study represents a preliminary investigation into the biological characteristics of CD44+CD24+ pancreatic cancer cells.

[Analysis of clinical effects of anterior segmental decompression for multi-segment cervical spondylotic myelopathy].

OBJECTIVE: To evaluate the clinical effects of anterior segmental decompression for the treatment of multi-segment cervical spondylotic myelopathy. METHODS: The clinical data of 84 patients with multi-segment cervical spondylotic myelopathy treated between August 2005 to March 2016 were retrospectively analyzed. According to different operative methods the patients were divided into control group and observation group, with 42 cases in each group. In the control group, including 26 males and 16 females, the age was (56.87±11.89) years old and course of disease was(7.91±3.71) years on average, the lesion segment occurred on C3-C6 of 36 cases and on C4-C7 of 6 cases. There were 24 males and 18 females in observation group, with the mean age of (54.58±12.56) years old, and the course of disease was(8.03±3.52) years, the lesion segment occurred on C3-C6 of 34 cases, and on C4-C7 of 8 cases. The patients in control group were treated with posterior laminoplasty, and the patients in observation group underwent anterior segmental decompression. Operation time, intraoperative blood loss, hospitalization time, bone graft fusion time and complication rate were observed between two groups. JOA scores and Cobb angle of fusion segment were compared before operation and 3, 6, 9 months after operation. RESULTS: Operation time, intraoperative blood loss, hospitalization time and complication rate in observation group were significantly lower than in control group(P<0.05); the bone fusion time in observation group was significantly lower than in control group(P<0.01);3, 6, 9 months after surgery, JOA score and the segment Cobb angle in observation group were significantly higher than in control group(P<0.01). CONCLUSIONS: Anterior segmental decompression for the treatment of multi-segment cervical spondylotic myelopathy has obvious advantages of less vertebral resection, thorough decompression, good stability, less postoperative complications, which can effectively promote the recovery of the spinal cord function and vertebral stability.

Digital radiography image denoising using a generative adversarial network.

Statistical noise may degrade the x-ray image quality of digital radiography (DR) system. This corruption can be alleviated by extending exposure time of detectors and increasing the intensity of radiation. However, in some instances, such as the security check and medical imaging examination, the system demands rapid and low-dose detection. In this study, we propose and test a generative adversarial network (GAN) based x-ray image denoising method. Images used in this study were acquired from a digital radiography (DR) imaging system. Promising results have been obtained in our experiments with x-ray images for the security check application. The Experiment results demonstrated that the proposed new image denoising method was able to effectively remove the statistical noise from x-ray images, while kept sharp edge and clear structure. Thus, comparing with the traditional convolutional neural network (CNN) based method, the proposed new method generates more plausible-looking images, which contains more details.

Enhancement of digital radiography image quality using a convolutional neural network.

Digital radiography system is widely used for noninvasive security check and medical imaging examination. However, the system has a limitation of lower image quality in spatial resolution and signal to noise ratio. In this study, we explored whether the image quality acquired by the digital radiography system can be improved with a modified convolutional neural network to generate high-resolution images with reduced noise from the original low-quality images. The experiment evaluated on a test dataset, which contains 5 X-ray images, showed that the proposed method outperformed the traditional methods (i.e., bicubic interpolation and 3D block-matching approach) as measured by peak signal to noise ratio (PSNR) about 1.3 dB while kept highly efficient processing time within one second. Experimental results demonstrated that a residual to residual (RTR) convolutional neural network remarkably improved the image quality of object structural details by increasing the image resolution and reducing image noise. Thus, this study indicated that applying this RTR convolutional neural network system was useful to improve image quality acquired by the digital radiography system.

Possible Involvement of F1F0-ATP synthase and Intracellular ATP in Keratinocyte Differentiation in normal skin and skin lesions.

The F1F0-ATP synthase, an enzyme complex, is mainly located on the mitochondrial inner membrane or sometimes cytomembrane to generate or hydrolyze ATP, play a role in cell proliferation. This study focused on the role of F1F0-ATP synthase in keratinocyte differentiation, and its relationship with intracellular and extracellular ATP (InATP and ExATP). The F1F0-ATP synthase ß subunit (ATP5B) expression in various skin tissues and confluence-dependent HaCaT differentiation models was detected. ATP5B expression increased with keratinocyte and HaCaT cell differentiation in normal skin, some epidermis hyper-proliferative diseases, squamous cell carcinoma, and the HaCaT cell differentiation model. The impact of InATP and ExATP content on HaCaT differentiation was reflected by the expression of the differentiation marker involucrin. Inhibition of F1F0-ATP synthase blocked HaCaT cell differentiation, which was associated with a decrease of InATP content, but not with changes of ExATP. Our results revealed that F1F0-ATP synthase expression is associated with the process of keratinocyte differentiation which may possibly be related to InATP synthesis.

Implantable wireless battery recharging system for bladder pressure chronic monitoring.

This paper presents an implantable wireless battery recharging system design for bladder pressure chronic monitoring. The wireless recharging system consists of an external 15 cm-diameter 6-turn powering coil and a silicone-encapsulated implantable rectangular coil with a dimension of 7 mm × 17 mm × 2.5 mm and 18 turns, which further encloses a 3 mm-diameter and 12 mm-long rechargeable battery, two ferrite rods, an ASIC, and a tuning capacitor. For a constant recharging current of 100 µA, an RF power of 700 µW needs to be coupled into the implantable module through the tuned coils. Analyses and experiments confirm that with the two coils aligned coaxially or with a 6 cm axial offset and a tilting angle of 30°, an external power of 3.5 W or 10 W is required, respectively, at an optimal frequency of 3 MHz to cover a large implant depth of 20 cm.

Design and validation of a fully implantable, chronic, closed-loop neuromodulation device with concurrent sensing and stimulation.

Chronically implantable, closed-loop neuromodulation devices with concurrent sensing and stimulation hold promise for better understanding the nervous system and improving therapies for neurological disease. Concurrent sensing and stimulation are needed to maximize usable neural data, minimize time delays for closed-loop actuation, and investigate the instantaneous response to stimulation. Current systems lack concurrent sensing and stimulation primarily because of stimulation interference to neural signals of interest. While careful design of high performance amplifiers has proved useful to reduce disturbances in the system, stimulation continues to contaminate neural sensing due to biological effects like tissue-electrode impedance mismatch and constraints on stimulation parameters needed to deliver therapy. In this work we describe systematic methods to mitigate the effect of stimulation through a combination of sensing hardware, stimulation parameter selection, and classification algorithms that counter residual stimulation disturbances. To validate these methods we implemented and tested a completely implantable system for over one year in a large animal model of epilepsy. The system proved capable of measuring and detecting seizure activity in the hippocampus both during and after stimulation. Furthermore, we demonstrate an embedded algorithm that actuates neural modulation in response to seizure detection during stimulation, validating the capability to detect bioelectrical markers in the presence of therapy and titrate it appropriately. The capability to detect neural states in the presence of stimulation and optimally titrate therapy is a key innovation required for generalizing closed-loop neural systems for multiple disease states.

A translational platform for prototyping closed-loop neuromodulation systems.

While modulating neural activity through stimulation is an effective treatment for neurological diseases such as Parkinson's disease and essential tremor, an opportunity for improving neuromodulation therapy remains in automatically adjusting therapy to continuously optimize patient outcomes. Practical issues associated with achieving this include the paucity of human data related to disease states, poorly validated estimators of patient state, and unknown dynamic mappings of optimal stimulation parameters based on estimated states. To overcome these challenges, we present an investigational platform including: an implanted sensing and stimulation device to collect data and run automated closed-loop algorithms; an external tool to prototype classifier and control-policy algorithms; and real-time telemetry to update the implanted device firmware and monitor its state. The prototyping system was demonstrated in a chronic large animal model studying hippocampal dynamics. We used the platform to find biomarkers of the observed states and transfer functions of different stimulation amplitudes. Data showed that moderate levels of stimulation suppress hippocampal beta activity, while high levels of stimulation produce seizure-like after-discharge activity. The biomarker and transfer function observations were mapped into classifier and control-policy algorithms, which were downloaded to the implanted device to continuously titrate stimulation amplitude for the desired network effect. The platform is designed to be a flexible prototyping tool and could be used to develop improved mechanistic models and automated closed-loop systems for a variety of neurological disorders.

Emerging technology for advancing the treatment of epilepsy using a dynamic control framework.

We briefly describe a dynamic control system framework for neuromodulation for epilepsy, with an emphasis on its practical challenges and the preliminary validation of key prototype technologies in a chronic animal model. The current state of neuromodulation can be viewed as a classical dynamic control framework such that the nervous system is the classical "plant", the neural stimulator is the controller/actuator, clinical observation, patient diaries and/or measured bio-markers are the sensor, and clinical judgment applied to these sensor inputs forms the state estimator. Technology can potentially address two main factors contributing to the performance limitations of existing systems: "observability," the ability to observe the state of the system from output measurements, and "controllability," the ability to drive the system to a desired state. In addition to improving sensors and actuator performance, methods and tools to better understand disease state dynamics and state estimation are also critical for improving therapy outcomes. We describe our preliminary validation of key "observability" and "controllability" technology blocks using an implanted research tool in an epilepsy disease model. This model allows for testing the key emerging technologies in a representative neural network of therapeutic importance. In the future, we believe these technologies might enable both first principles understanding of neural network behavior for optimizing therapy design, and provide a practical pathway towards clinical translation.

Micro package of short term wireless implantable microfabricated systems.

Package is a critical part in biomedical implantable systems. Many factors affecting the host body and the life time of implantable systems need to be considered. Package becomes more critical for microfabricated systems with wireless charging and communication. This paper presents the first phase study on micro package techniques for short term (30 to 90 days) implantable systems. A MEMS implantable telemetry model system was designed for packaging evaluation. The transmitter was custom designed and fabricated using MOSIS processes and an external receiver was designed and built for data collection. For short term implantable systems, medical grade silicone outer coating is used for "tissue compatibility"; while multilayer polymeric and nanometer-thin metal or ceramic films were used for inner coatings to provide mechanical strength and to block vapor and moisture penetration. The total coating thickness is less than 0.6 mm. The electrical performances (leakage resistance) of test board and model devices coated with various package materials and processes are evaluated in 40 degrees C saline. This paper presents: the model system; the evaluation methods and analysis of failure modes of polymeric coating on test boards; the solution to the failures and suggested coating techniques of polymeric materials; and the evaluation of model systems packaged with multi-layer coatings in 40 degrees C saline. The expected performance of developed packaging method was verified by experiments. Implantable wireless MEMS system can be packaged with thin multilayer materials to have an expected life time greater than 30 days.

An implantable bi-directional brain-machine interface system for chronic neuroprosthesis research.

An implantable bi-directional brain-machine interface (BMI) prototype is presented. With sensing, algorithm, wireless telemetry, and stimulation therapy capabilities, the system is designed for chronic studies exploring closed-loop and diagnostic opportunities for neuroprosthetics. In particular, we hope to enable fundamental chronic research into the physiology of neurological disorders, define key electrical biomarkers related to disease, and apply this learning to patient-specific algorithms for therapeutic stimulation and diagnostics. The ultimate goal is to provide practical neuroprosthetics with adaptive therapy for improved efficiency and efficacy.

Novel long-term implantable blood pressure monitoring system with reduced baseline drift.

A novel long-term less-invasive blood pressure monitoring system with fluid-filled cuff is proposed for advanced biological research. The system employs an instrumented elastic cuff attached with a rigid isolation ring on the outside wall of the cuff. The cuff is wrapped around a blood vessel for real-time blood pressure monitoring. The elastic cuff is made of bio-compatible soft silicone material and is filled with bio-compatible insulating silicone oil with an immersed MEMS pressure sensor. This technique avoids vessel penetration and substantially minimizes vessel restriction due to the soft cuff elasticity, thus attractive for long-term monitoring. A rigid isolation ring is used to isolate the cuff from environmental variations to suppress baseline drift in the measured waveform inside the monitoring cuff. The prototype monitoring cuff is wrapped around the right carotid artery of a laboratory rat to measure real-time blood pressure waveform. The measured in vivo blood waveform is compared with a reference waveform recorded simultaneously by using a commercial catheter-tip transducer inserted into the left carotid artery, showing matched waveforms with a scaling factor about 0.03 and a baseline drift of 0.6 mm Hg. The measured baseline drift is three times smaller compared to using a cuff without a rigid isolation ring.