Poster Session



Poster Section III –Biomechanics, Cell/Tissue Engineering, Medical Imaging

Dec. 2, 2018 11:00 AM - 12:00 PM


Shih-Chung Chen, Ia-Chen Tsai, Wei-Lun Chen, Wen-Ting Li and Chung-Min Wu

Abstract-With the rapid development of science and technology, including the development of artificial intelligence and robotic arms, simple and easy-to-operate assistive equipment for caring people has emerged on the market. In addition to helping people with severe disabilities to solve their needs, it also reduces the bur-den of care. The industrial robotic arm can perform visual identification, force sensing, and precise point correction. When there is an error in the position or there is a problem with the mechanical arm status, it can also make an immediate correction or emergency stop to ensure the safety of the user. Therefore, this study uses an industrial robotic arm to capture the pacifier-type input switch of the Morse code controller to the disabled, so that the severe disabled can operate the computer with the help of a pacifier switch alone without other people’s help.


Ichiro Hieda, Yoshiko Nakamura and Ryohei P. Hasegawa

AIST is developing augmentative and alternative communication (AAC) systems for people with severe motor disabilities, who frequently develop the minimal communication state (MCS) or the totally locked-in state (TLS). For the TLS people, we are developing the “Neurocommunicator” (NC), an EEG-based communication aid. In this study, we have applied the core technologies of NC to the “Blinkcommunicator” (BC), a new AAC system for MCS people. This system is applicable to the patients who can blink or at least can excite the eye muscles to blink. The signals associated with blinks have better signal-to-noise ratio than an event-related potential (ERP) that is used by NC. Moreover, it is easy to install the electrodes for BC because only two electrodes should be put on the forehead and the earlobe, respectively. The users can select the target by blinking their eyes when the target pictogram flashes across a LCD. Although the latency of a blink is typically 500ms not as fast as the ERP, BC is designed to detect the signal during the quick flashes of the pictograms (4 or 8 Hz) on behalf of the pattern-matching method. We examined the accuracy of the target detection during the BC operation of 11 healthy adult volunteers. The average accuracy was around 91% for 4Hz cycles of the single flash of each pictogram that was as high as accuracies of NC (around 90-95% for 8Hz). These results suggest that BC is promising to become a practical communication aid for MCS people.


Chia-Wei Min, Yu-Kai Wang and Po-Lei Lee

Analyzing monitoring body posture are importation for rehabilitation evaluation in disabled patients. To accurately acquire subject's postures, measurements of accelerations and rotation using inertial measurement unit (IMU) has been regarded as an effective tool. However, current commercial IMU-posture systems are expensive and not wireless which results in limited space of available moving range. In our research, we have developed a wireless IMU-based posture acquisition system. By placed 11 IMUs on body to detect entire motions from shoulder to foot. Each IMU contains a 9-Axis Gyro-Accel-Magnet meter and a Wi-Fi module. The system collects values from IMUs and analyzed using Quaternion algorithm then corrected by an embedded PI-controller in real-time. The angles and moving distances of different body parts were recorded. This system has been applied to measure posture changes in stroke patients during rehabilitation in Taoyuan hospital. By assessing the posture changes in patients, we hope this proposed system can help physicians to make personal prescription for better rehabilitation effect.


Yu Fang Chen, CHOU KUOFENG, CHIANG YUEH JU and TANG RUI JIE

The motivation of this study is to solve the problem that the passivation of elderly to the pressure source such that pressure ulcers are easily formed in the shoe due to the aging of the tactile receptor, the peripheral nerve atrophy and the peripheral nerve conduction slowing down. The purpose of this study was to create a wearable in-shoe pressure detection system with easy-to-use features. The pressure values of the four in-foot pressure points of the shoe that can easily generate pressure sores were measured, and the device can determine whether it is too high. This design can monitor the pressure in-shoe regardless of the static or walking state. The wearable in-shoe pressure detection system consists of an elastic sock containing four pressure sensors, a micro-processing chip for signal reception and transmission, and a mobile application program. The pressure sensor has a pressure range of 0~2kg and a diameter of 10mm. The four disc-shaped sensors are distributed on the tip of the toe of the sole, the heel, ball of the big toe and the joint of the small toe joint. The research process firstly measured the sensing curve and obtained the characteristic equation. Using Apps Inventor to programming the mobile application to convert the sensor output to the pressure and set the safety threshold. If the pressure is too high, The responded point on the mobile phone would display red color, the responded point is green if the pressure is near the threshold, and if the pressure is below the threshold the responded point would display blue. The sensor signal is filtered by the microprocessor chip, then converted into a digital signal and transmitted to the mobile phone through the Bluetooth module. Experiments were carried out to test three different styles of sample shoes of the same size and other three sample shoes of the same style and different sizes. The in-shoe pressure detection system developed in this study can be applied to select the best fitting shoes for the elderly or patient to keep their foot health.


Su Yaling and Yu-Yao Wang

The AV access is usually evaluated by feeling thrill and pulsa-tion through palpation, listening for the bruit by using a stethoscope, Doppler ultrasound imaging, or angiography, etc. However, these techniques require specific equipment and operator. Phonoangiography is a noninvasive tool for identi-fying vascular diameter change. In this study, a mock model has been set up to simplify the simulation of blood flow condi-tion. Phonographic signal is recorded by electronic stetho-scope and further signal processed. The relationship of pho-nographic signals and stenotic lesions is studied. Early detec-tion of hemodialysis access problems such as stenosis and thrombosis is very important issue. The purpose of this study is to develop a phonographic system to evaluate arteriove-nous shunt (AVS) stenosis of hemodialysis patients. The de-gree of stenosis (DOS) is used as an index to classify the AV access condition, and is determined by the narrowing per-centage of normal vessels. The empirical mode decomposition (EMD) method is applied to analyze the relationship between DOS and spectrogram. After feature extraction, use machine learning to train pre-diction model and classify. Verification is based on Doppler ultrasound which is the golden standard in clinical application. In 22 cases, KNN and SVM show 90.9% and 85.7% accuracy respectively, it proved that empirical mode decomposition is feasible in feature extraction. This noninvasive method may be useful and potential for early detection in home-care use.


Hsin-Chieh Chen, Hai-Ning Ho, Yan-Xiang Zhang, Yi-You Hou and Tsung-Ju Li

According to the Ministry of the Interior statistics, the ageing index of Taiwan reached 105.08% in 2017, so that the ageing population is increasing. The elders who due to degeneration of the body, "muscle weakness" is the main factor affecting the quality of life, so most silver-haired people need care. In order to effectively improve the quality of life and assist in strengthening muscle function, this study will implement a powerful assistive device system combined with Internet of Things (IoT) technology. The developed device can to help the silver-haired people to enhance the palm force. Furthermore, this device collects hand-held information through the IoT technology and application in the palm rehabilitation. It is hoped that the system will analyze the patient's condition online and improve the benefit of rehabilitation. The system is use the microprocessor (Adafruit Feather M0) to send and receive data by Wi-Fi technology. Further, this system builds up the finger aids model by using 3D printing technology, set a pressure sensor get the force data on end of the fingertip, and upload those data to the website through the microprocessor. This finger aids model connected the wire to pull-push the finger joint that performs flexion and extension exercises. Through the experimental results, the effectiveness of system function has confirmed, and it will apply to clinical verification in the future.


Li-Wen Lin and Pao-Hsin Liu

Literatures revealed that mandibular fracture accounted for 19% to 40% of facial fractures which were demonstrated it required treatment urgently. Moreover, the fixation treatment with screw fixations could cause to get hurt in some nerves. Hence, bone screw could be inserted with angle deviation slightly to provide better stability and decrease a risk of nerve injury. The aim of this study is to investigate biomechanical effects of polyaxial screw insertion in the mandibular symphysis fracture by finite element analysis. The model was consisted of fractured mandible, screw, rotator and plate. The muscular forces of close mouth were applied to simulate biting for mandibular fracture fixation to evaluate stability of the polyaxial screw fixation. The parameters in three types of screw-inserted angles and two kinds of length in the plate were studied for this study. The result indicated that the eight-pores-length plate with five degrees of screws insertion could provide the best stability. The fixation of the polyaxial-screw-plate system can reduce stress concentration on the mandibular efficiently.


Ming-Ze Kao, Min-Che Chun, Chien-Chang Chen and Shu-Chen Liu

Purpose: The magnetic fields are widely used in medical devices, particularly in the field of oncology. Yet, mechanisms underlying the biological effects of static magnetic field (SMF) are relatively unexplored. Here, we established an in vitro model system to study the biological effects of SMF in cancer cells. Methods and Materials: The SMF were generated through the arrangement of Halbach magnet arrays with magnitudes ranging from 100mT to 220mT. Each magnet array provided an increasing gradient from center to border by an increment of 6.857mT/mm. The cell line, derived from the nasopharyngeal tumor biopsy, was cultivated for 48 hours for experiments such as flow cytometry, western blotting and time lapse observation. Results: Results of flow cytometry showed that SMF exposure resulted in a higher S-phase accumulation of cells compared to control group after 24-hour continuous exposure (42.95 % vs. 35.08 %). In addition, SMF also caused a delayed G2/M progression (% of G2/M, SMF vs. control: 10.78 % vs. 4.63%). Western blotting data revealed an increased activation of DDR responses which bring about ATM-NBS1-CHK signaling pathway in SMF-treated cancer cells. Moreover, time-lapse proliferation test suggested that cancer cells stimulated with high gradient SMF affected cell proliferation and performed tumor cells regression by means of the combination treatment with 5-flourouracil drug. Conclusions: Our data showed that high gradient SMF caused M-phase arrest, which potentially sensitizes the cancer cells to genotoxic chemodrugs. Further evaluation of the anticancer therapeutic efficacy by utilizing high-gradient magnet fields in combination with genotoxic drugs are undergoing.


Ming-Tzu Tsai, Shang-Huan Peng, Chia-Wei Hsu, Yu-Ting Wang and Yi-Juan Wang

Mechanical stimulus plays a critical role in the growth and development of osteoblasts and bone tissues. To determine the effect of cyclic stress on the osteogenic gene expression, a novel cyclic stress stimulator with multi channels has been developed and applied to MG-63 cells in this study. The stimulation parameters were designed with a programmable power supplier and different weights of liners, sticked to magnets. To determine whether the cyclic stress affect the osteogenic gene expression in MG-63 cells, total RNA was collected at 1, 6, and 24 h after CS stimulation. Cells were cultured onto a 6-well culture plate at 5105 cells/cm2 and incubated at 37°C in 5% CO2 overnight for the cell attachment. The results showed that CS-treated cells expressed higher gene expression of ALP and Osx at 24 and 1 h after the CS stimualtion. However, BMPR1A, Dlx-5 and BSP gene expression of the CS-treated groups decreased at each assay time point compared to the untreated groups. It revealed that the cyclic stress stimulation may have the capatibility involving in the osteogenic gene expression. Further study is essential for the discussion of the possible mechantransduction.


Yi-Ching Chen, Chien-Ju Lin, Hsiao-Feng Chieh, Li-Chieh Kuo, Po-Ting Wu, I-Ming Jou, Yen-Liang Lai, Chun-Ta Lai and Fong-Chin Su

Patients with carpal tunnel syndrome (CTS) undergo carpal tunnel release (CTR) surgery to relieve the pressure on median nerve by incising the transverse carpal ligament (TCL). However, it is reported that 6.3% to 21.9% of CTR patients develop trigger finger (TF). Absence of the TCL may be the factor for causing TF after CTR. It may lead to excessive volar migration of the flexor tendon and “bowstringing” phenomenon. Therefore, it is hypothesized that applied force on the carpal tunnel may eliminate the bowstringing effect of the tendon. Thus, the purpose of this study is to investigate the effect of different compressive force at the carpal tunnel on the flexor digitorum superficialis (FDS) tendon. Five healthy adults were included. The subject performed slow-ramped maximum voluntary isometric contraction (MVIC) with the middle finger in PIP joint 60° flexion at wrist 30° flexion. The transducer of ultrasound synchronized with a load cell was utilized to apply 2, 4, 6, and 8 N compressive force, respectively, on the carpal tunnel transversely and record images simultaneously. The normalized tendon positions decreased as compressive force increased in the rest condition. It showed a descending tendency in the exerting force condition. The results indicated that applied force on the carpal tunnel eliminates the movement of tendon. The tendons moved volarly, which may cause the tendon force at the carpal tunnel. In the exerting force condition, the normalized tendon migration with 6 and 8 N were much greater than 2 and 4 N. The tendon force in-creased with increasing compressive force. When applying 6 and 8 N force, the increase of tendon force became small. It may be restricted by the TCL and reach the critical value.


Mu-Yi Liu, Po-Liang Lai, Tsung-Ting Tsai, Jin-Kai Chen and Ching-Lung Tai

Background: Pedicle screw fixation in the lumbar spine has been widely accepted as an effective method to treat a wide range of spinal disorders. The traditional trajectory (TT #1) technique is to insert the pedicle screw follow a lateral to medial trajectory (Transverse Plane), in which the sagittal trajectory of the screw is parallel to the superior endplate of the vertebral body. In our pre-vious experience, to lengthen the screw anchoring length, the traditional trajectory technique was further modified to insert the pedicle screw in a way with identical lateral to medial trajectory, but superior to inferior (Sagittal Plane) until near to the lower end plate of vertebral body in the sagittal trajectory (TT # 2). Recently, cortical bone trajectory (CBT) was developed as an alternative to traditional trajectory in the lumbar spine. In contrast to traditional trajectory, CBT follows a caudal to cephalad and medial to lateral trajectory, which takes advantage of a mostly cortical path. Previous reports have demonstrated that numerous factors, such as bone quality, screw design, and screw fixation technique are related to screw anchoring strength. However, until now, few reports are available to systematically assess the biomechanical performance of the aforementioned three different screw trajectories. This study is thus aims to investigate the effects of different screw trajectory (TT # 1, TT # 2, and CBT) on screw stability following screw instrumentation. Methods: Standard synthetic single vertebrae (Model: ERP#3429-4-2; L4) are used as substitute for human bone. To ensure the accuracy of screw placement, computed tomography (CT) images of synthetic vertebra and 3D printing technology were used to create three templates (guide device) with different trajectories as previous described. Following screw insertion, screw pullout tests for each group (six specimens in each group) was performed using a material testing machine. Results: Traditional Trajectory TT #1 presented the lowest pullout strength (589.06±152.33 N) among three groups (P < 0.05). How-ever, no significant difference in pullout strength was observed between Traditional Trajectory TT #2 (589.06±152.33 N) and Cortical Bone Trajectory (629.70±108.29 N) (P > 0.05). Conclusions: We concluded that Traditional Trajectory TT #2 and Cortical Bone Trajectory effectively enhance screw fixation strength.


Fang-Chuan Kuo

Background and Purpose: Squat-to-stand is a type of closed-kinetic chain movement with a small base of support. It requires strong lower extremity strength and dynamic stand-ing balance. This study aimed to investigate postural stability and musculoskeletal control during the squat-to-stand task in older adults. Methods: Twenty-four older adults (OA) and 24 younger adults (YA) were assessed for posture stability during standing up from a squatting postition using a balance system. Electromyography and kinematic data of head, trunk and lower extremity were recorded simultaneously. Results: The OA group had a larger stability index in the anterior-posterior direction than the YA group. The maximal angle displace-ments and angular velocity of the knee joint were significantly lower in the OA group than in the YA group. The OA group also used more head flexion in the first half of the movement cycle but less lateral flexion in the latter half of the cycle than the YA group. The OA group required greater activation of the hip and lower extremity muscles to stand up. The onset of erector spinae muscle activity occurred earlier in the OA group than in the YA group, whereas the onset of the gluteus medius and gastrocnemius muscles was later. Conclusions: Kinematics and neuromuscular modulations are changing with aging. Older adults need to adjust velocities of moving joints and increase the extensor muscles of the back and thigh to provide posture stability.


Yi-Chun Tsai, Chien-Hsien Yeh, Chih-Chun Lin, Kai Chang, Ping-Han Chuang, Li-Chieh Kuo and Fong-Chin Su

Ankle foot orthoses (AFO) that restrict the ankle joint movement were commonly used for stroke patients to prevent from drop foot. This study investigated the kinematics and kinetics effect of customized 3D-printing AFO (3DP AFO) on gait in stroke patients. Three subjects with chronic hemiparetic stroke were recruited in this study. The gait performance of these subjects with and without 3DP AFO was compared using motion capture system and force plates. The 3DP AFO designed in this study have positive effects of preventing drop-foot during swing phase and improving push-off force genera-tion during terminal stance. Further studies needs to be con-structed to recruit more subjects and to analyze the effect of 3DP AFO on different functional subgroup patients.


Shao-Ting Chao

In this study, a complete numerical model was established for the generation and pathogenesis of open-angle glaucoma, and the simulation mechanics analysis was discussed. The open glaucoma of the horn is caused by the lesion of the trabecular meshwork, which causes the drainage of the aqueous humor in the eye to be blocked, so that the increase of the intraocular pressure at the anterior chamber of the anterior chamber af-fects the pressure accumulation in the posterior chamber, and the posterior chamber pressure is transmitted to the optic nerve to cause defects in the visual field. With blur. This study will enable patients with glaucoma to better un-derstand their related morbid conditions and provide future medical information and reference data.


Chia-Kang Chang and Cheng-Lun Tsai

Silicone is a material with flexible, heat resistant, and biocom-patible material properties. Since sensors with a soft touching surface is generally preferable for wearable medical devices, a 3D printer using silicone material allows a fast prototyping of such sensors. The printing speed is mainly determined by the curing time of silicone. Even though silicone sealants generally take over thirty minutes to dry to the touch, a thin line width printing using small nozzle diameter can accelerate the curing process. To have a uniform line width, the inner pressure of silicone is detected to feedback control the compression of silicone paste. The accurate curing time is determined by experiment. Higher environment temperature and high relative humidity are also helpful in saving the curing time.


Shao-Ting Chao

This study explores open-angle glaucoma and its Pathogenesis to create the whole Numerical model and Mechanical analysis. Open-angle glaucoma is caused by pathological changes of trabecular meshwork. Intraocular aqueous fluid will be stuck and intraocular pressure will increase in both anterior and posterior chamber. Then, intraocular pressure of posterior chamber diffuses and oppress optic disc, causes the blurring and disability of sight. This study apply two software, 3D Design software PROE and Finite element method simulation software ANSYS, to create mode and related simulation of open-angle glaucoma. This simulation analysis helps us to understand pressure distribution of glaucoma and where the stress gathers in different Cup-disc ratio. From the analysis of the results of the open-angle glaucoma in this study, it can be clearly seen that the intraocular pressure is too high due to the anterior chamber pressure. From the perspective of the whole eye, the stress and strain at the posterior sclera, optic disc and optic nerve tissue are relatively large, because the three structural tissues are located at the back end of the eyeball, and the pressure will be transmitted through the front direction. It makes it easy to cause stress concentration and serious damage. Think in terms of locality, and then explore the different degrees of cup-to-disk ratio. Different people and age differences, each of the different differences affect the chance of suffering from glaucoma.


Chi-Chia Liu and Jin-jia Hu

Material testing system is common for quantification of stiffness of material. MTS is lack of inner information because it is usually done by optical camera, and ultrasound system could go through the object. We combine a customized unit-axial tensile test system and ultrasound system with 35 Mhz frequency single element transducer to observe the inner change of material when doing stretching test. We choose poly(vinyl alcohol) gel as phantom, because we can control its stiffness by freeze and thaw cycles. The tensile test sys-tem use step motor to drive ball-screw, and capture ultrasound signal and the strength which is read by load cell at regular dis-tance. Then, we use 2D cross-correlation between frame and frame to calculate the strain. By doing so, we can get stress-strain curve and the Young’s modulus. We also compare the result with commercial VIC-2d system. From this result, we think that it is feasible to quantitate the material’s stiffness measured by the ultrasound and unit-axial ten-sile test system.


Shuen-Wen Chan, Yi-Yun Ke, Che-Min Chiu and Zong-Hong Lin

Pathogenic bacteria are the major organisms responsible for various water-borne and food-borne diseases in the world, thereby causing threat to human life. As a measure to control this problem, we propose self-powered disinfection system composed of a multilayered triboelectric nanogenerator (m-TENG) and conductive fabric which can scavenge energies from daily human activities and convert it to electric energy. This electrical energy can be used to perform electroporation assisted disinfection. The results shows that developed system displays great disinfection performance towards Escherichia coli (E. coli) because of the electroporation effect. In order to improve the disinfection performance, the fibers were coated with gold-coated tellurium nanowires (Au-Te NWs) which can strengthen the local electric field. The increased local electric field enhances the electrical output which further improves the disinfection performance. Furthermore, due to the fiber-based structure of the disinfection device, this system can be incorporated into the commercial textiles to design smart antibacterial clothes which can have a great potential in contributing towards a healthy society.


Jong-Hong Lu, M.T. Cheng, Y.T. Fang, S.C. Huang, Y.M. Kao and D.Y. Wang

At present, there are about 2 billion people in the world have myopia. It's estimated that there will be 4.7 billion people with myopia in 2050, and 900 million of them will be at risk of blindness due to high myopia. The age of occurring age-related retinal macular degeneration is reduced from 60 years old to 40 years old, and the dramatic increase in the exposure of the eye to the artificial light source blue-violet light may be the main cause. Therefore, myopia lenses combined with anti-blue light functions have become a mainstream. However, we still require blue light in daily life, such as the requirement for color perception, eye pupil dilation, and physiological clock, etc., so we can't completely and directly separate the blue light in 400 nm to 500 nm. In this study, based on ISO 8980-3:2013(E), ISO 12609-1:2013(E), and ISO 12609-2:2013(E), we calculated, analyzed and evaluated blue light transmittance (traffic sign recognition) of anti-blue myopia lenses on the market used to protect the eye. In addition, we designed a blue light bandpass filter based on the blue light hazard weighting function through the short-circuit current measured by the photodiode, the blue light hazard-weighted transmittance, and blue light irradiance can be analyzed easily and quickly.


SHUHAN WEN, Shu-Jen Chiang, Ting-Hsuen Wu, Hsu-Cheng Huang, Pei-Jung Lee, Ji Wang, Shih-Chi Chen, Huei-Wen Chen and Chen Yuan Dong

Cancer is a serious disease worldwide and remains is one of the leading causes of death. Therefore, precise and personalized treatment of cancer patients is an im-portant frontier of modern medicine. In this study, we demonstrate the efficacy of the use of precisely cut tu-mor slices for drug testing in the mouse model. We found that the application of drug yielded similar results as in vitro testing using cell lines. The technique we demon-strate may be extended for better drug testing in the future.


Zhu-Xuan Lu, Yen-Zhen Liu, Yu-Yi Wu, Yong-Fang Lin, Ze-Ru Li, Yu-Lun Lyu and Pei-Ru Chen

Scaffoldsthat possess adequate biodegradability, pore size, inter-connectivity, bioactivity and mechanical properties in accordance with the injured tissue are required. This work aimed to develop and characterize three-dimensional(3-D)scaffolds that fulfill the aforementioned requirments. a nozzle-based rapid prototyping system was used to polylactic acid and thermoplastic elastomer to fabricate 3-D biodegradable scaffolds with two patterns (orthogonal and displaced double layer). Contact angle tests were also performed on PLA and TPE to evaluate their hydrophilicity and hydrophobicity.


Ciao-Yi Syu, Cong-Han Xiao, Yu-Lin Shen, Ching-Cheng Huang and Ho-Yi Hung

Supercritical carbon dioxide is a rapidly developing technology in recent years, Supercritical carbon dioxide can provide a benefit of high diffusion ability in nature product extraction process, can preserved the thermo unstable and keep the bioactivity of the extracts. a cell extraction process was used to remove  cellular  components  by porcine dermal.The porcine dermal must remove fat and other impurities almost by supercritical fluid(SCF),  otherwise adipose tissue  will become rot immediately. For collagen scaffold samples, dermis were hydrolyzed by alcohol type of different. In  the  present study, the uniform  porcine dermal with SGS security lable, it was obtained by designed machine. It get dermis exactly and quickly via a machine which was  designed from our team(power-driven dermatome, SIACIN international, SC -GST).


Cong-Han Xiao, Ciao-Yi Syu, Yu-Lin Shen, Ching-Cheng Huang and Hsiao-Chih Hu

This started provide a new method for Preparations of Collagen films with Extra Cellular Matrix via Treatments of Supercritical Carbon Dioxide Fluid and NH4OH.Tissue engineering combines knowledge of engineering materials and medical applications to find more undiscovered things through this knowledge. Extracting bioactive collagen from the skin and bone of animals is a hot topic in recent years. The cell scaffold and collagen are obtained by removing the cell matrix and subcutaneous fat from the porcine dermal and the obtained collagen is mostly insoluble. However, these fat cells are wrapped under collagen fibers to cause difficulty in extraction. This study mainly relies on the effects of supercritical fluid and ammonia on the removal of subcutaneous fat and impurities from porcine dermal. Electron microscopy showed the effect of supercritical fluid and aqueous ammonia at different times on ECM of porcine dermal tissue.


Wei-Che Hong, Wei-Huang Wang, Ming-You Shie, Yi-Wen Chen and Yu-Fang Shen

Cartilage does not have vascular and mature chondrocytes have limited proliferative capacity, so cartilage regeneration is considered to be difficult compared to other tissues. In this study, a cartilage scaffold was prepared by digital light processing (DLP) 3D printing technique, and hydrogels with encapsulated cells were added to the scaffold in combination with bioprinting technologies. Animal studies have shown that this hybrid scaffolds can help to repair the damaged cartilage tissue and help the development of cartilage tissue engineering.


Tie-Kun Peng and Hsin-Yi Lin

In this experiment, a porous scaffold was made by 3D printing. The experiment was divided into control group and experimental group. The control group was alginate scaffold without chitosan coating. The experimental group was alginate scaffold coated with chitosan. Three kinds of antibiotics (Ampicillin, Tetracycline Hydrochloride, Chloramphenicol) with similar molecular weights were used as drug carriers in drug delivery systems to study their drug loading, drug release rate and antibacterial ability (inhibition zone). The chitosan content, mechanical strength, degradation rate, cell activity test were discussed. The experimental results showed that about 1003.5±62.31 μg of chitosan was coated on scaffold in the experimental group. For the mechanical strength test, the young’s modulus and the ultimate tensile strength of the experimental group were 0.43 MPa and 0.22 MPa, respectively, which were higher than the control group of 0.14 MPa and 0.10 MPa. Degradation rate test, the degradation rate of the experimental group was about 12.98%, which was significantly lower than that of the control group (22.47%). Drug release rate test, the release rate of the experimental group was slower than that of the control group, because coated chitosan can slow down drug release. Antibacterial ability test, the experimental group and the control group containing antibiotic scaffolds against Gram-negative bacteria (E. coli), Gram-positive bacteria (S. aureus) bacteriostatic test, found that all have antibacterial effect. Finally, human fibroblasts(CRL-2522) were seeded on the scaffolds of the experimental group and the control group containing antibiotics for 1, 4, and 7 days, and the cells gradually increased with the number of days, and the amount of TypeⅠcollagen also increased. The above results show that the experimental group is coated with chitosan, which enhances the mechanical strength and slows down the degradation rate. After adding antibiotics to the scaffold, not only can slowly release enough antibiotics to inhibit bacteria, and it will not hinder skin repair.


Bo Wei Chen and Hsin-Yi Lin

This experiment produced a double-layer composite scaffold to repair damaged cartilage tissue and subchondral bone. Using the rapid prototyping system to make a porous scaffold with chitosan and pectin as a material to imitate the subchondral bone , and then the dense nanowire-like structure is covered by electrospinning with chitosan, pectin and polyvinyl alcohol as materials to imitate cartilage tissue. In order to maintain the nanofiber structure of the electrospinning layer of the composite scaffold for a long time, the composite scaffold strengthens its nanofiber structure by cross-linking with glutaraldehyde , and the physical properties test and cell culture in vitro are discussed the effect of the composite scaffold on cartilage tissue and subchondral bone repair. The results of the degradation test showed that the nanofibers of the electrospun layer of the composite scaffold were immersed in the salt buffer solution, and remained nanofibrous after 21 days. The electrospun nanofiber structure was similar to the natural extracellular matrix. Maintain the structure and properties of chondrocytes. When the osteoblasts are implanted on the rapid prototyping scaffold layer of the composite scaffold, the intensity of compression increases with time, indicating that the osteoblast secretes the medullary protein osteocalcin, and the cells gradually deposit calcium ions and phosphate ions, resulting in the deposition of calcium ions and phosphate ions. The compressive strength of the stent is increased. The interactions between chitosan–pectin networks were studied using Fourier Transform Infrared Spectroscopy (FTIR). In the biocompatible part, observing the osteoblasts by scanning electron microscopy revealed that the cells were stacked on the scaffold on the 21st day, and the chondrocytes remained in the electrospinning layer on the 21st day. It does not have a large number of forms that become fibroblasts. The results of DNA showed that osteoblasts and chondrocytes could proliferate smoothly on the composite scaffold. The alkaline phosphatase activity of osteoblasts was highest at 14 days, and collagen quantification is getting lower and lower with the number of days of experimentation. Calcium Quantification was highest on day 21, and these results showed that the osteoblasts gradually differentiated into bone cells as the number of days of the experiment increased. Glycosaminoglycan quantification of chondrocytes revealed a significant increase from day 4 to day 21, indicating that the chondrocytes remained globular and normally secreted glycosaminoglycans.


Ching-Wei Lang, Jui-Kang Kuo and Po-Ling Kuo

Both physical and chemical factors can have a great influence on the change in extracellular matrix (ECM) which is a highly dynamic structure that undergoes continuously remodeling. Cell-ECM interactions have critical roles in many physiological and pathological conditions. Hydrostatic pressure (HP) and interstitial fluid pressure (IFP) both are important physiological factors that cause great effect on cell-ECM interaction. A polymethylmethacrylate (PMMA)-based 3D cell culture device which applies HP and IFP with tunable pressure drop generating controllable interstitial flow velocity is used in our study. The shear-wave elasticity image (SWEI) system is also used to quantify the tissue elasticity and record in real-time with a non-invasive way. In this study we demonstrate how HP and IFP play roles in 3D cell-matrix interaction and quantify the effect caused by them.


Hui-Chun Huang, Ting-Yun Wang, Jeng-Jiann Chiu, Yi-Shuan Li, Yingxiao Wang, Shu Chien and Chia-Ching Wu

Vein graft failure is triggered by the loss of venous endothelial cells (vEC) after venous-to-arterial flow transition. Focal ad-hesion kinase (FAK) is important for assembling the focal adhesion (FA) for cell anchorage, but the mechanoresponses of vEC under arterial flow in regulating FAK remains unknown. We transfected vEC with GFP-FAK or FRET-Src plasmids prior to subjecting them to arterial laminar shear stress (ALSS, 12 dyne/cm2). Each cell was divided into upstream and downstream region by a line drawn perpendicularly to flow through the central nucleus, and the spatial-temporal FA dynamics for FAK assembly/disassembly and Src activations were quantified. In comparison to arterial EC (aEC), vEC showed smaller FA size and higher FA number with delaying FAK assembly/disassembly under ALSS. The ALSS-induced spatial activation of FRET-Src at cellular upstream region also was not seen in vEC. Inhibiting FAK in arterial cells abolished the ALSS-induced FA dynamics and resulted in vEC phenotype with cells peeling off. Application of epithelial growth factor to vEC activated Src and FAK to rescue FA dynamics and the loss of vEC. This study highlights the importance of FAK-Src dynamics in vEC as a crucial factor for mechanoresponses to prevent graft failure.


Yu-Yi Wu, Yong-Fang Lin, Zhu-Xuan Lu, Yen-Zhen Liu, Ze-Ru Li, Yu-Lun Lyu and Pei-Ru Chen

Neuroengineering is a study that everyone focuses on in recent year due to nerve repair is always a difficult target. Silk fibroin(SF) is a biocompatible and slowly biodegradable biomaterial with excellent mechanical properties that could meet the above stated requirements, the main function is to support our scaffold. Moreover, Chitosan(CS) is a widely exist chitin in natural environment, and partially deacetylated to get chitin.it has also been shown to have wound healing property, to be nontoxic,and to have minimal foreign body response with accelerated angiogenesis. In this study, we used SF solution combined with CS solution in several concentration and loaded in suitable molds than freeze-dried to produce SF-CS scaffold. After that, we will cultured PC12 cell on the scaffold than investigated up to 8 weeks in phosphate buffer saline(PBS) solution at 37°C and some examinations.


Szu-Ching Chen, Yi-Jen Hsueh, Hung-Chi Chen and Chieh-Cheng Huang

Human corneal endothelial cells (CECs) possess extremely limited regenerative potential. Dramatic loss of CECs results in endothelial dysfunction, thus leading to corneal edema and opacity and can be sight-threatening. Currently, corneal transplantation remains the only solution to improve patients’ visual acuity. However, worldwide shortage of donors continues. Additionally, the endothelial density of the harvested donor cornea can be reduced owing to various factors and thereby less than the threshold required for transplantation. Typically, a high pre-operative endothelial cell density is required in order to offset the postoperative cell loss and ensure graft survival. Biomaterial-based culture platform with enhanced structural support may provide a route for increasing the cell density of donor corneas or engineering artificial corneas. In this work, a three-dimensional (3D) stimuli-responsive fibrin gel with customizable stiffness is developed as a scaffold for cultivation of corneas. The converting enzyme thrombin is encapsulated into gelatin carrier system before mixing with fibrinogen and various amounts of porogen particles. Films that are formed by direct mixing of thrombin and fibrinogen are used as control. By adjusting the ratio between thrombin and fibrinogen, the mechanical property of the fabricated fibrin gel can be modulated. Our in vitro results demonstrated that the as-prepared fibrin gel exhibits suitable biocompatibility. A rabbit model of corneal endothelial dysfunction for penetrating keratoplasty will be established to determine if the primary or artificial corneal buttons treated by the aforementioned protocol can effectively reduce the rate of primary graft failure.


Xiang-Yu Gao, Meng-Hsuan Hsieh, Song-Yi Wu, Jun Wu, Shu-Hong Li, Hao-Ji Wei, Ren-Ke Li and Hsing-Wen Sung

Myocardial infarction (MI) is generally caused by the occlu-sion of coronary artery, inducing fibrosis scar formation around the infarction, leading to abnormal electrical signal propagation and cardiac arrhythmia. In this work, a self-doping conductive polymer was synthesized by grafting the conductive poly-3-amino-4-methoxybenzoic acid (PAMB) onto the biocompatible gelatin and then chemically crosslinked by EDC/NHS to form a hydrogel (PAMB-G), which can be inject-ed into the MI tissues to support electric conduction, thus improving cardiac function. The results of the in vitro study demonstrated that PAMB-G facilitated electrical signaling propagation and enhanced field potential, as confirmed through the calcium signaling analysis and microelectrode (MEA). An ex vivo Langendorff-perfused beating heart was developed to evaluate the biological conduction through the synthesized PAMB-G hydrogel. The obtained data suggested that PAMB-G hydrogel may support conduction between tissues at a distance, implying its potential capability to rebuild electrical impulse propagation across the scarred tissue in an in vivo setting. The PAMB-G was injected into the MI area of rats, and the results showed that a significant improvement of heart functions, such as reduced induced arrhythmia and spontaneous arrhythmia, improved conduction velocity, and increased fractional shortening, was achieved. The above results clearly demonstrated that the PAMB-G hydrogel can improve electrical impulse propagation across the scarred tissue and electrically bridge the scar barrier between healthy myocardium, thus, resulting in better preservation of ventricu-lar function.


Wen-Chien Hsu, Ting-Yuan Tu, Wen-Tai Chiu, Chia-Hsuan Cheng and Ping-Ching Wu

Today, the fatality rate of cancer has remained higher and higer. However, the methods commonly used to treat cancer patients include surgical resection, traditional chemotherapy, and radiation therapy. These treatments are directed at cancer cells, but always ignore the environment maybe promotes the cancer cell growth through the the other pathways. This study established a 3D tumor microenvironment model in vitro. In this model, tumor cell invasion or migration is inhibited by modulating the phenotype of macrophages. Breast cancer tumor spheroids were cultured using a low-attached round-bottom 96-well plate, and co-cultured macrophages and breast cancer cells into spheroids in the same way. Embed the sphere into the collagen to create a simple 3D tumor microenvironment model. By transfecting pEGFP-N1 into 4T1 cells and allowing breast cancer cells to have green fluorescence, cancer cell invasion can be observed in a microenvironment model. Our results showed the effects of macrophages on cancer cells in different co-culture models, including cancer cell invasion and migration. This study investigated the effects of different phenotypes of macrophages (M0, M1 and M2 phenotypes) on cancer cells in co-culture models, including cancer cell invasion and migration.


Chao-Lin Chen, How-Ran Guo and Jin-Jia Hu

Atherosclerosis and its sequela including stenosis of coronary artery or peripheral artery are the major causes of morbidity and mortality among people in the modern society. Following battles to find the “Holy Grail” of applicable functional vascular grafts for over 50 years, small-caliber(<6mm) ones are still craving in many clinical applications. Here we introduce a concept of cultivating tubular tissue with cyclic mechanics in vivo – dynamically generated intraperitoneal tubular tissue, which might be a new hope for various clinical applications. Rats were purchased from the animal center of NCKU. All experimental protocols had been reviewed and approved by the Institutional Animal Care and Use Committee of NCKU. Rats over 4 months old were implanted a custom-made silicone tube, with a segment in peritoneal cavity and two openings left on the skin. After a 7-day recovery period after surgery, they were connected to syringe pumps which generated cyclic pressurization and resulted in a inflation/deflation effect of implanted silicone tubes. Pressure were monitored by detectors and recorded using a custom software. Connections with pumps for mechanical stimulation were set 8hr/day, with different pumping speed/frequencies. After 1-month of incubation, animals were sacrificed for tubular tissue analysis and mechanical tests, including burst pressure, pressure-compliance, and suture retention force. An optimal burst pressure of over 50 psi (3.5kg/cm2) was measured for those with cyclic mechanical stimulation, and differences between pumping and control group were significant. Suture retention force ranged from 50g to over 100g. We observed a significant association between wall thickness and the mechanical test results. Despite some limitations, this pilot experiment showed a new method to generate autologous tissues inside the recipient’s own body with no risk of rejection. We are now working on further studies to make it more practical .


Tzu-Chieh Huang and Chia-Ching Wu

Excessive inflammation within damaged tissue usually leads to delayed and insufficient regeneration. The macrophages are recently categorized into pro-inflammatory type1 macrophages (M1) and anti-inflammatory type2 macrophage (M2). In peripheral nervous system, modulating the inflammatory response to promote nerve regeneration has become more and more promising. Thrombomodulin (TM) is a transmembrane glycoprotein containing five domains. The lectin-like domain of TM shows ability in suppressing inflammatory response. However, the effectiveness of TM application for immune modulation to promote nerve regeneration is still unknown. Here, we investigated the profile expression of M1 and M2 macrophages on transected sciatic nerve and evaluated the therapeutic effect of TM for nerve regeneration via immune modulation. We discovered that TM treatment allowed a better nerve regeneration and further preserved effector muscle function. A decrease in the number of infiltrating macrophage with TM treatment indicated the anti-inflammatory capacity of TM at the injury site of nerve. We also revealed decrease of M1 macrophage marker CD86 and increase of M2 macrophage marker CD206 after the application of TM. The role of TM for switching M1 to M2 was confirmed by in vitro administrating TM to THP1 cell. In light of these results, we conclude the anti-inflammatory ability of TM as a potential drug to promote peripheral nerve regeneration through convergence of M1 to M2 for achieving better functional recovery.


Chia-Wei Huang, Shih-Yu Lu, Tzu-Chieh Huang, Liming Bian and Chia-Ching Wu

Schwann cells (SCs) play an important role in myelinating and supporting the axon in peripheral nerves. The seeding of adipose-derived stem cells (ASCs) on chitosan-coated microenvironment was demonstrated to promote sphere formation and differentiate ASCs into a mixed population of neural lineage cells (NLCs) that contains nestin, neural filament heavy chain, and glial fibrillary acidic protein (GFAP) positive cells. Here, we discovered the profiles of fibroblast growth factor receptor (FGFR) during sphere formation were significantly increased for FGFR2 and FGFR4, but decreased for FGFR3. Since fibroblast growth factor 9 (FGF9) regulates neural cell fate during embryo development, the effect of FGF9 on ASC-derived NLCs was tested by adding FGF9 peptide during NLC induction. FGF9 reduced sphere size and switched the NLCs toward SCs by increasing the GFAP and specific SC marker, S100. Transient Akt phosphorylation was observed at 6 hr in FGF9-induced NLCs (FGF9-NLCs). By specifically knocking-down each FGFR using shRNA, the silencing of FGFR2 diminished Akt phosphorylation and inhibited the SC fate commitment. The FGF9 or fate committed FGF9-NLCs were applied into the nerve conduit to test the therapeutic potential on the sciatic nerve of rat. Direct FGF9 injection caused severe scar formation and blocked nerve regeneration. However, transplantation of FGF9-NLCs participated and formed myelin sheath-like structure that promotes axon regrowth. Knockdown of FGFR2 in FGF9-NLCs prohibited cell participation which caused nerve regeneration to fail. Therefore, this study reveals the importance of FGF9 in Schwann cell fate determination via the FGF9-FGFR2-Akt pathway and demonstrates the therapeutic benefit of FGF9-NLCs.


Wei-Cheng Hsu, Yueh-Sheng Chen, Ming-You Shie and Chun-Hsu Yao

In our previous study, we found that gelatin-based materials exhibit good conductivity and are non-cytotoxic. In this study, gelatin was cross-linked with bisvinyl sulfonemethyl (BVSM) to fabricate a biodegradable conduit for peripheral nerve repair. First, BVSM on the prepared conduit was character-ized to determine its mechanical properties and contact angle. The maximum tensile strength and water contact angle of the gelatin-BVSM conduits were 23 ± 4.8 MPa and 74.7 ± 9°, which provided suffi-cient mechanical strength to resist muscular contraction; additionally, the surface was hydrophilic. Cyto-toxicity and apoptosis assays using Schwann cells demonstrated that the gelatin-BVSM conduits are non-cytotoxic. Next, we examined the neuronal electrophysiology, animal behavior, neuronal connectivi-ty, macrophage infiltration, calcitonin gene-related peptide localization and expression, as well as the expression levels of nerve regeneration-related proteins. The number of fluorogold-labelled cells and histological analysis of the gelatin-BVSM nerve conduits was similar to that observed with the clinical use of silicone rubber conduits after 8 weeks of repair. Therefore, our results demonstrate that gelatin-BVSM conduits are promising substrates for application as bioengineered grafts for nerve tissue regen-eration.


Lee Kai Xing Alvin, YEN-HONG LIN, MING-YOU SHIE and YI-WEN CHEN

There is a need for development of novel and op-timal bone substitutes to overcome increasing cases of bone defects and disorders. In recent years, bioactive calcium sili-cate (CS) cements have been introduced as a potential candi-date for bone substitutes. Calcium silicate have excellent bioac-tivity and is known to be able to induce bone-like apatite formation which enhances osteogenesis. A recent self assem-bled polyphenol modification of calcium silicate surfaces has further prove to enhance cellular behaviors. Inspired by the natural properties of plants, this modification was prepared by polymerization of polyphenol onto calcium silicate surface to mimic chemical compositions found in plaque-substrate inter-face. In this study, caffeic acid (CA) was chemically immobi-lized onto the surfaces of CS scaffolds to investigate whether CA surface modified CS scaffolds were able to provide a suita-ble micro-environment for cellular activities. Initial results showed that our 3D-printed CA-CS scaffolds not only exhibit-ed excellent mechanical properties under compressive strain tests, but also displayed enhanced cellular adhesion and supe-rior apatite formation when compared to neat CS scaffolds. In addition, in-vivo studies displayed superior bone regeneration and in-growth of bone tissues into scaffolds. These initial re-sults support the premise that such CA surface modified scaf-folds had the potential to be used as a biomaterial for applica-tion in bone tissue engineering in the future.


Tai-En Hsieh, Sheng-Ju Lin, Chun-Chieh Chen, Po-Liang Lai and Chieh-Cheng Huang

Clinically, insufficient blood perfusion after fracture and the resultant tissue hypoxia can lead to delayed bone healing or even nonunion. As a crucial molecule to life, oxygen is required in several cellular processes, such as aerobic respiration, en-zyme activation, cell differentiation, collagen synthesis, that are involved in fracture healing. Therefore, a major hurdle in pro-moting bone regeneration is to provide sufficient oxygen to support the survival and function of the newly formed tissue. In this work, a composite oxygen-generating system consisting calcium peroxide (CaO2), manganese dioxide (MnO2), citric acid encapsulated poly lactic-co-glycolic acid (PLGA) for im-proving local oxygenation and enhancing fracture healing. Once exposed to water, solid CaO2 particles can generate hy-drogen peroxide (H2O2), which can be further converted into oxygen under the catalysis of MnO2. According to our experi-mental results, this composite oxygen-generating system can surely produce oxygen,and the release time can sustain up to over 3 days. In the future, we will o further test to encapsulate the different amount of CaO2, MnO2, citric acid and optimize the data of the system.


Jheng-Yang Wang, Szu-Han Chen, Yuan-Yu Hsueh and Chia-Ching Wu

Surgical nerve decompression for compressive neuropathy is the widespread standard procedure and most patients have satisfied outcomes for symptom relief. However, the patients still suffered from neuropathic pain resulting from new, residual or recurrent compression neuropathy after surgeries. The severity of mechanical compression plays an important role for peripheral neuropathy. By means of reviewing previous animal models published for compressive neuropathy, there were no reproducible results in terms of tension-controlled. Therefore, we established a modified animal model of tension-controlled compressive neuropathy in rat sciatic nerve in order to analyze resultant functional nerve outcomes. We established a modified animal model for compressive neuropathy under different tension stretch and then evaluate the behavioral function of injured sciatic nerve. The muscle atrophy and nerve degeneration were measured by histological assessments. We would also survey the neuro-inflammation and vascular disturbance in the regenerated nerve by using immunohistochemical (IHC) staining. We observed peripheral compressive neuropathy made behavior exchanged on the affected leg of rat including sensory dysfunction and muscle atrophy. If the mechanical force compressed stronger, nerve degeneration and muscle weakness made more severe. Those behavior results in the new animal model of peripheral compressive neuropathy were similar to clinical findings in humans. In our findings, we also found the mechanical compression proportional to nerve degeneration and neuro-inflammation. In the future, we will confirm the new mechanism-based treatment by surgery or medication on the animal model to provide more efficient outcomes with lower side effect. We hope to make benefit mankind and science with our research.


yinghsiu lin and Po-Hsiang Tsui

Nonalcoholic fatty liver disease (NAFLD) is a type of hepatic steatosis that results in advanced liver diseases. Ultrasound imaging provides fast screening and qualitative descriptions of NAFLD. To assist in the diagnosis by physicians, quantitative evaluation of NAFLD is highly required clinically. Note that liver steatosis results in changes in several sonofeatures, in-cluding echo intensity, attenuation, and speckle pattern. Therefore, compared to using the individual feature, combina-tion of the above three sonofeatures may provide more clues and physical meanings to improve the accuracy for NAFLD examinations. In this study, we proposed a machine learning-based diagnostic approach based on ultrasound multifeatures for the assessment of NAFLD. The patients with different degree of steatosis were recruited and divided into two groups: Groups A (n=111) and B (n=74) were used for training and testing in the analysis of machine learning, respectively. For each patient, the percentage of liver steatosis was estimated using pathological section images (>10% was used to identify diseased cases). A commercial ultrasound scanner equipped with a 3-MHz convex transducer was used to acquire envelope data for calculating the parameters, including the integrated backscatter (IB, a measure of echo intensity), Q factor (pro-posed as a new estimate of frequency downshift due to attenu-ation), and homogeneity factor (HF, a new parameter pro-posed to describe the speckle pattern). Support vector ma-chine (SVM) based on different kernel functions (linear, radial basis function (RBF), and polynomial) was used to com-bine the above three parameters for comparisons of accuracies between single- and multifeatures in NAFLD as-sessment. Each parameter is able to discriminate between normal and fatty patients. Importantly, SVM-based multifeatures ap-proach allows characterization of NAFLD with the highest accuracy (86.49%) and area under the receiver operating characteristic curve (AUROC; 0.8899). Ultrasound multifea-tures based on machine learning improve the accuracy for NAFLD diagnosis.


Jheng-Ru Chen

Ultrasound scattering occurs when the wavelength of an incident ultrasound signal is greater than the sizes of scatterers in a tissue, and the scattering results in a speckle pattern in a B-mode image. A lot of statistical models were proposed to describe the statistical distributions of backscattered signals for tissue characterization. One constraint to employing physically based statistical models for fitting the distribution of backscattered statistics is that the distribution of the backscatter envelope data must conform to the used distribution. The mentioned condition renders statistical models inapplicable to ultrasound tissue characterization. Among all possibilities, information entropy demonstrates the highest potential and flexibility for analyzing ultrasound backscattering. Compared with the distribution parameters, estimating entropy does not require the backscattered data to follow a specific distribution, thus providing the opportunity to establish methods that are more flexible in practical applications. Recently, some literature reported that sample entropy is a modification of approximate entropy, used for assessing the complexity of time-series signals, diagnosing diseased states without significant dependency on the data length. To explore the ability of sample entropy in detecting the properties of scatterers, phantom experiments were performed to investigate sample entropy as a function of scatterer concentration. The experimental results showed that sample entropy is able to differentiate changes in the number density of scatterers. In particular, the optimal dimension and tolerance used for estimating sample entropy were also confirmed in this study. This report is the first to reveal the potential of sample entropy in ultrasound tissue characterization.


Chiao-Shan Hsieh

Previous studies have confirmed that the statistical distribution of ultrasound backscattered signals is consistent with the Nakagami model theory, and thus the Nakagami statistical model is often used to identify the arrangement and concentration of the scatterers in the tissue. A lot of literature further explored the algorithm of ultrasound Nakagami parametric imaging, which has been successfully applied to the description of tissue microstructure properties. Recently, AmCAD Biomed Corporation commercialized Nakagami imaging technology as the AmCAD-US software that has obtained FDA approval for listing. The purpose of this study was to evaluate the performance of AmCAD-US software on detecting the variation of the scatterer concentration by exploring the relationship between the Nakagami parameter (m value) and the scatterer concentration. Phantom experiments were performed for validations of the software. The results show that with the increase of the scatterer concentration, the m-parameter value obtained by the AmCAD-US software analysis rises and approaches 1, indicating that the statistical distribution of the backscattered signals gradually approaches the Rayleigh distribution. In particular, the correlation coefficient between the m parameter value and the scatterer concentration is 0.99. This study confirmed that the AmCAD-US software performs well in characterizing the scatterers. Due to the launch of AmCAD-US software, the quantitative analysis of ultrasound images will play a key role in the field of clinical diagnostic assistance and radiology research.


Kun Yang

High-intensity focused ultrasound (HIFU) has been widely applied to noninvasive thermal therapy. To control the quality of HIFU treatment, localization of the heating point in tissues is necessary. Among all possibilities, ultrasound imaging is able to provide useful clues associated with the temperature information; in particular, changes in backscattered energy (CBE) constructed using time-domain signals allow parametric imaging to visualize temperature distribution of tissue. However, conventional time-domain CBE imaging is insensitive to visualizing the HIFU heating point. In this study, we developed single-phase and frequency-domain CBE imaging to improve the sensitivity of conventional CBE imaging.Phantom experiments were conducted. A clinical ultrasound scanner equipped with a convex array transducer of 3 MHz was used to collect radiofrequency signals during HIFU for B-mode and CBE imaging based on time-domain, single-phase, and frequency-domain technique. The sensitivity to localize the HIFU heating point was evaluated by calculating the image contrasts and correlation coefficients between temperature and magnitude of pixels in each kind of image.The experiment results showed that frequency-domain CBE imaging produced the highest image contrast (12.06 ± 3.33 dB) in visualizing the heating point of HIFU compared to the other types of CBE images. The magnitude of CBE obtained from the frequency-domain CBE image also highly correlated with the temperature change (correlation coefficient = 0.88).Ultrasound frequency-domain CBE imaging may be considered as a useful technique to enhance the sensitivity to localize the treatment point during HIFU.


T.S. Hsieh, C.F. Lu, C.Y. Chen and Y.C.J. Kao

Independent component analysis (ICA) has become an important analytical method of data-driven analysis for functional MRI (fMRI). In human, the effect of IC number has been proposed. However, there is lack of consensus on selection of the optimal IC number for rodent fMRI. Group ICA (gICA) was performed in 22 rats underwent high-resolution rsfMRI protocol. IC number of 10 to 100 were used to evaluate the effect on functional segmentation in the somatosensory cortex and thalamus. The functional network in the somatosensory cortex was detected under low IC number (IC number = 10), while the network in the thalamus appeared at IC number larger than 40. Most of regions in the somatosensory pathway segregated with larger IC numbers. The maximum value of Z also increased as the function of IC numbers. Our finding with systemic evaluation of IC number effect on rats fMRI suggests that the more subnetworks in the cortex can be detected using larger IC number. IC number over 40 is essential to detect reliable thalamic networks using data-driven ICA in rats.


Cheng-Yu WU, Jenn-Lung Su, Lung Chan and Yao-Hsun Tein

Alzheimer's disease (AD) is caused by the deterioration of the brain nerves. Due to the irreversible of AD, it’s important to diagnose accurately as early as possible. In this work, a computer-aided detection (CAD) system was developed to not only predict the Clinical Dementia Rating(CDR) of patients, but provide physicians with more objective quantitative data from CT images to assess the degree of deterioration of AD. This CAD system was developed based on the correlation between Clinical Dementia Rating (CDR) and the brain atrophy ratio. Volume of brain parenchyma, specific sulcus, volume ratio of ventricle to skull from CT images were calculated through image pre-processing, region growing, threshold, image enhancement, and morphological skeleton. All of these parameter was then used in Support Vector Machine(SVM) to interpreting CDR scores. 60 sets of CT images were used (40 sets as training groups & 20 sets as test groups) to train and test this system. Effectiveness of the system and classifiers was performed by using the comparison with CDR and MRI images of patients, and receiver operating characteristic(ROC)analysis. SVM classifiers were trained in 11 groups of parameters such as brain parenchyma ratio, left and right brain parietal sulcus, left and right brain central sulcus, left and right lateral sulcus, cerebral ventricle, third ventricle, cerebral cistern and whole ventricle. 20 groups of testing data were used to test the efficiency of the classifier. The accuracy, sensitivity, specificity, and Kappa value of the obtained classifier were 80%, 86.6%, 84.6%, and 0.547, respectively; if the cases with significant difference in brain parenchymal volume ratio and CDR level were excluded, the efficiency could up to 88%, 100%, 84.6% and 0.699, respectively. Results show that the system not only has a grate diagnosis performance, but also has similar system performance compared to mainstream MRI-based algorithms.


Ho-Chiao Chuang

In the study, we developed a tumor motion model to detect the tumor position in the lung with real-time ultrasound. The tumor motion model was made using the Ultrasound Image Tracking Algorithm (UITA) with a 4-Dimensional Planning Computed Tomography (4DCT). This method could be applied to radiotherapy about the tumor position compensation technology. In the experiment, we made the three different tumor motion models before the tracking error verification experiment. We made the tumor motion models by the 4DCT. The verification experiment used the Cone Beam Computed Tomography (CBCT). In the validation experiment, the each tumor motion model did five signal sports (four pre-recorded human respiratory signals and one Sin wave). The tumor motion model was created by using UITA to monitor the superior-inferior (SI) trajectory of the diaphragm and using 4DCT to monitor the tumor in SI and medial-lateral (ML) at the same time. The model parameter include center position, amplitude ratio, and phase. The tracking error verification experiment was compare the estimated tumor trajectories and the real tumor trajectories. The estimated tumor trajectories was the UITA uses model transformations to predict tumor position in SI and ML. The actual tumor trajectories was CBCT records the actual tumor position. The CBCT image is record the tumor position in the phantom. The ultrasonic image records the diaphragm position. The diaphragm displacement is converted into the tumor displacement by the prior tumor motion model. About 90 seconds of simultaneous acquisition of CBCT and UITA were analyzed. The error parameter analyze in the most error model. The phase error deviation does not exceed 12% of the length of the respiratorycycle.


Hsin-Hua Chen, Yi-Ming Chen, Yu-Wen Fu and Hsian-Min Chen

Introduction: Psoriasis is a chronic, immune-mediated inflammatory skin disease and affecting about 125 million people worldwide. It ranges in severity from a few scattered red, scaly plaques to involve-ment of almost the entire body surface. Currently, clinicians use visual and haptic methods for diag-nosis the disease severity. This does not help them in stratification and risk assessment of the lesion stage and grade. Further, current methods add complexity during monitoring and follow-up phase. The current diagnostic tools lead to subjectivity in decision making and are unreliable and laborious. For these reasons, we need a more objective, precise, and reproducible method to assess skin in-volvement. In this paper, we present a new snapshot hyperspectral imaging approach to real time processing algorithms for evaluation of skin involvement. Our goal is to lay out the benefits of this technique for quantitative evaluations of skin features. Materials and Methods : Snapshot HSI was obtained using the Hyperspectral imager (OCI-2000™, BaySpec, California 95131 USA). Wave length coverage ranged from 600nm to 1000nm with 25 spectral bands. Image resolution was 210 x 410 pixels in each spectral band. In this study, Spectral Angle Mapper (SAM) was used to calculate the difference between two reflectance spectra of healthy skin and psoriasis. To establish a HSI database of normal skin, we enrolled 39 healthy controls (HC). In total, 19 males and 20 females with median age 48 years (range, 22-66 years) and no apparent skin diseases were enrolled as a reference group. Additionally, one patient with psoriasis was also recruited. Results and Conclusions : In this paper, three preliminary conclusions can be obtained: First, there is a great difference in spectral waveforms between the areas of psoriasis, uninvolved psoriasis and HC skin from the SAM value measured by spectral similarity. Second, standardized spectral profiles from the HC group along with healthy skin from a psoriasis patient demonstrate an increased signal at wavelengths of 706 to 850 nm. However, the standardized spectral profile from the psoriasis patient has a large vari-ation at 700 to 850nm. The spectral profile after 850nm was also different from that in the HC group. Finally, colored Visualized Spectral Profile Mapping (VSPM) figures of intra- and inter-variance analysis clearly demonstrate the areas of increased SAM changes. We could identify the area of pso-riasis lesion through use of VSPM. In conclusion, our preliminary results shed light on the potential clinical application of snapshot HSI when diagnosing and treating psoriasis skin disease.


Nai-Yuan Chiang, Chuan-Yi Lin, Shou-I Chen and Szu-Wei Huang

Lanyu Miniature pigs are widely accepted as an animal model in Brain science research and brain medical device testing. Most medical devices like surgical guidance system require animal testing before clinical testing in the same environment and peripherals. However, there is neither standard nor protocol on clinical MR (Magnetic Resonance Imaging) for Lanyu Miniature pig. Literature on the MR parameters of Lanyu Miniature Pig is sparse. Therefore, it was the purpose of this study to generate MR parameters of the normal brain of Lanyu Miniature Pig by the use of a 3T Magnet. In this study, 3 Lanyu Miniature Pigs weight in 30-50 Kg provided by National Laboratory Animal Center, NARLabs was chosen as subjects. All experiments were performed in accordance with the National Laboratory Animal Center Ani-mal Experiments Guidance. The Philips 3.0T magnetic reso-nance scanner (Philips, Achieva X Series, Amsterdam, Nether-lands) was used to take T2W imaging in fixed FOV (80mm* 80mm) mode. Adjust the main MR parameters TR, TE, and voxel size to find the optimal parameters. Results showed that using the parameters recommended by the original manufacturer for clinical use (voxel size=0.6*0.8*1, TR=3000, TE=90), images were blurred and could not show the structure of thalamus and pons. According to our experi-ment, the parameters were set to: voxel size=0.4*0.4*2, TR=3000, and TE=80 as optimal parameters which result showed clear thalamus, pons and cerebral nerve bundle. The MR parameters of Lanyu Miniature pigs established in this experiment can provide better image quality for the research team to acquire more accurate data for the validation and evaluation of medical device development.


Chi-Ho Tseng, Men-Tzung Lo and Yi-Syuan Sung

Otitis media (OM) is a disease prevalent among pediat-ric, and adult population as well. The diagnosis of otitis media in children is sometimes not easy. It requires the alertness of the parents and the clinical experience of the doctor. It must also be coordinated with some in-struments, equipment, and other objective inspection, in order to provide accurate diagnosis. With the advance-ment of computer vision and Internet of things, it is possible to do real time analysis for aiding the OM di-agnosis by using a digitized otoscope. Professional ENT (Otolaryngology) doctors can use the digitized otoscope to capture a favorable eardrum image for analysis and diagnosis. However, it is not suitable for common home user. Due to lack of anatomical structure knowledge of the middle ear, users may capture an image without the eardrum on it, resulting in bad analysis outcomes. Therefore, we want to add a semi-automatic eardrum tracking program to the device, which can be used to capture the complete eardrum based on the ear-drum illustration diagram and a guided arrow. Our results demonstrated that this semi-automatic eardrum track-ing algorithm has acceptable accuracy of 90.43 % for total images. Among them, the accuracy of 95.66 % for normal images, the accuracy of 84.92 % for AOM, the accuracy of 87.88 % for COM and the accuracy of 84.11 % for OME. The cost-effective algorithm can assist parents for early detection and continuous monitoring at home to decrease consequence of the disease.


JyhWen Chai, Hung-Chieh Chen, Yi-Hsin Tsai, Hsin Tung, Hsian-Min Chen and Clayton Chi-Chang Chen

Background and Purpose: Spontaneous intracranial hypotension (SIH) has historically been understood to be a direct manifestation of low CSF pressure caused by leaks of spinal CSF and as an important cause of orthostatic headache (OHA). Currently, magnetic resonance imaging (MRI) has revolutionized the diagnosis of SIH confidently instead of invasive procedures. Although SIH is usually described as benign, it can lead to severe complications and even multiple arterial strokes with deaths in the situations of a delayed diagnosis. The reason would be that the radiological presentations, as well as the clinical manifestations, are highly diverse and the initial misdiagnosis is common. Based on measurements of pulsatile cerebral blood and oscillating CSF flow, the MR-based intracranial pressure (MR-ICP) method has been proposed for noninvasively estimating the cerebral hemodynamics and intracranial hydrodynamics. The aim of our proposal is attempted to detect changes in cerebral hemodynamics and CSF hydrodynamics in patients with clinical manifestations of typical OHA, with and without typical MR imaging patterns of SIH. using MRI flow studies, in an effort to improve diagnostic sensitivity and further investigate the pathophysiology. Materials and Methods: The subject consisted of 35 SIH patients with typical OHA and 10 patients with typical OHA due to CSF leakage after lumbar puncture and spinal operations. 20 healthy young volunteers were also recruited for comparison. In 32 equally divided frames of cardiac cycle, the blood flows of internal carotid arteries, vertebral arteries, internal jugular veins, and CSF flow in cervical spinal canal were obtained using phase-contrast MRI. The intracranial volume change (ICVC) was obtained by summing all flows before a cardiac frame, and the peak-to-peak CSF pressure gradient (PGcsf-pp) was deduced using the Navier-Stokes equations. The intracranial elastance (IE) was then derived from the ratio of PG and ICVC. Results: 35 SIH patients with the typical OHA were divided into 2 groups with and without the presence of epidural venous dilatation (EVD) in the high cervical spine. The EVD-positive group had significantly higher IE than those of the SIH patients without EVD and the normal volunteers. Contrarily, the EVD-negative group had significantly lower IE and PGcsf-pp than the normal volunteers and the EVD-positive group. The OHA patients with CSF leakage after lumbar puncture and spinal operation had no decrease in IE or PGcsf-pp as compared with the normal volunteers. Additionally, the MRI flow study showed significant decrease in transcranial inflow and outflow of SIH patients. Conclusions: MR-flow study is potentially more sensitive than the morphological MRI in early diagnosis and useful in understanding the pathogenesis of SIH. Contrary to common belief, our results suggested that an abnormal cerebrospinal elastance might be the cause of SIH, instead of CSF leak.


Wang Chiao-Yin, Chih-Horng Wu and Po-Hsiang Tsui

Radiofrequency ablation (RFA) has been widely applied to liver tumor treatments. Monitoring temperature during ablation is im-portant to avoid harming healthy tissues. Among all guidance tools, ultrasound not only provides real-time feedback of the electrode location for RFA guidance but also enables visualization of the tissue temperature. Changes in the backscattered energy (CBE) has been investigated for detecting variations in temperature distribution in the tissue. However, when RFA electrodes are inserted into tissues, some artifacts occur to degrade the quality of CBE imaging. In this study, we proposed freehand single-phase CBE imaging for monitoring clinical RFA without influences of CBE artifacts. Clinical experiments on the patients that were scheduled to undergo RFA treating liver tumors were conducted in Taiwan University Hospital. During RFA, a commercial ultrasound machine equipped with a convex transducer of 3 MHz was used to ac-quire backscattered signals every one minute in a freehand manner. The results were further compared with those obtained from computed tomography. The preliminary results showed that freehand single-phase CBE imaging is able to depict temperature distribution of the ablation zone. In particular, no significant CBE artifacts occurred to affect monitoring thermal dose. These findings suggested that freehand single-phase CBE imaging has potential in evaluating clinical RFA outcome in the periablation period.


Chiang Hsien-Wen, Tzu-Chao Chuang, Hsu-Ting Yen, Xiaoming Zheng, Hsien-Jen Chiang, Jung-Hui Li and Li-Han Lin

Open surgery has been gradually replaced by endovascular surgery in recent decades in treating patients with aortic pathology such as aneurysmal formation, aortic dissection or rupture that are associated with high mortality rates. As endovascular surgery has to be performed under X-ray fluoroscopy, it is unavoidable that surgeons will be exposed to ionizing radiation. The aim of this study is to evaluate the radiation dosages received by surgeons when performing these operations. Simulation experiments have been carried out by employing ATOM human prosthesis as patient and mannequin as surgeon under realistic surgical conditions. Radiations doses were recorded at locations of lenses, thyroid gland, chest and limbs under exposure modes of fluoroscopy and DSA (digital subtraction angiography). The effective doses received by the cardiovascular surgeons during aortic stent implantations were found to be 5.29 µSv or 5.62 µSv wearing protective lead clothing and glasses which is safe under current legislations of radiation protection. It is recommended that surgeons should wear protective devices at all time during surgical operations.


Hung-Yi Chen, Hsien-Yi Chiu, Kaun Yu Hsieh, Sheng-Jen Cheng, Han-Chun Tsai and Guan-Yu Chen

Clinically, dermatologists usually use Nail Psoriasis Severity Index (abbreviate as NAPSI) to diagnose and assess the severi-ty of nail psoriasis. However, due to the convenience and sub-sidy of health insurance in Taiwan, outpatient clinical usually needs to face hundreds of patients every day, doctors are lack-ing in time to diagnose each patient firmly. Therefore, we pre-sent a simple, fast and automatically NAPSI system by using one of the deep learning frameworks, mask R-CNN. In addi-tion, we design a standard photographic system that could capture patients’ clinical signs, setting up our own normalize datasets so we do not have to do the pre-process before train-ing our model. We hope our system could reduce plenty of diagnosis time on each patient and gain more information about the disease simultaneously, support dermatologists to make more precisely treatment.


Chun-Tai Chen and Bao-Yu Hsieh

Based on the dramatic difference of acoustic impedance between the bone and the surrounding soft tissue, the acoustic energy is partially reflected and scattered at the boundary, which can clearly show the contour of the bone. However, due to the irregular anatomy of the spine, the conventional B-mode image is difficult to show the complete spinal contour. In this study, the angle compounding imaging was used to enhance the contour of the spine in the image. Different imaging acquisition of the number of synthetic images and the acquiring angle of the image are compared. The optimized condition is with 13 images with the interval of 2.5° to show the high quality spine image.


Hong Jin Su, Deepa, Yashbir Singh, Shi Yi Wu and Wei-Chih Hu

Atrial fibrillation is a quivering of heartbeat that can lead to blood clots, stroke, heart failure, and other heart-related complications. It can affect adults of any age group, but it is very frequent in older people. It affects about 7 in 100 people aged over 65. More men than women have atrial fibrillation. In this work, we used CT images of ten different frames at ten different time axis and applied precise transformations to make dynamic internal heart pumping system that shows the dynamic structure of each atrium and ventricle. Before performing, The CT scan, we injected contrast media into the blood for the visibility of blood flow in the heart to obtain the images. Moreover, the resulting images are obtained from different time axis which is equivalent to the 4Din respect to original 3D. This study also suggests to find the dynamic of heart function, total compliance of vascular tree, observe stroke volume change atrial of appendix and evaluation of the outcome of radio ablation of fibrillation by this technique.


ZhongXuan Zhang, Liang-Xin Wang, Chia-Yen Lee and Yi-Chen Yeh

Clinically, pathological sections are used to discriminate the state of the tumor. Such as tumor size, degree of invasion, cancer staging, and provide the doctor to choose the appropriate treatment, so pathologists are crucial for the interpretation of the slice. However, pathologists mostly analyze pathological sections manually. Increased pathologist's misjudgment due to prolonged observation, so it is important to develop a computer-aided diagnostic system to count all the cells on the slice. Traditionally, counting cells must identify and divide the cell boundaries by image features. During this process, problems such as cell overlap, uneven staining, and inconspicuous cell boundaries occur. Deep learning can extract target features by analyzing a large amount of data, which is more accurate than the features extracted by observation in traditional algorithms. In this study, the deep learning model Faster-RCNN and Mask-RCNN were applied to the ki-67 pathological section for counting. Obtain the boundary type and number of pathologically sliced cells. The feature matrix extraction network for object detection uses ResNet to adjust the parameters and use the original image of the pathological tissue slice for network training. We adjusted the parameters and used the original image of the pathological tissue section for network training. The results show that Ki-67 stained slice cell detection with the existing deep learning network can achieve 90% accuracy, and more importantly, the computation time can be greatly reduced. This method drastically reduces the computation time, including training phase and testing phase. This study confirms the feasibility of using the same deep learning network for cell counting in Ki-67 pathological sections. We expect to build a more efficient cell counting method by adding image pre-processing and modifying the network architecture.


Hsin-Yu Chen, Ze Wang, Ming-Wei Lee, Sheng-Pin Tseng, Hui-Yu Tsai and Meei-Ling Jan

Prompt-gamma Compton imaging (PGCI) is a potential method for real-time proton range verification. Usually scintillation detectors with thick, high atomic number crystals are chosen as Compton absorbers to get higher efficiency to absorb full energy of Compton scattered photons. However, an absorber with the thicker crystals will cause a Compton camera the worse spatial resolution, if the absorber is without depth-of-interaction (DOI) capability. Continuous DOI detectors are usually using LSO or LYSO scintillators with crystal length <20 mm for 0.511 MeV positron imaging applications. But for the PGCC imaging, the specific PG energy lines interested are 4.44, 5.21, 6.13 MeV or even higher. Therefore, an absorber with LSO/LYSO crystal length thicker than 20 mm shall be more appropriate. In this work, effects of surface treatment and light sharing on depth-encoding absorbers using thick crystals with dual-ended readouts were studied. The detector module comprised a 3 × 3 array of polished and unpolished LYSO crystals with the cross section 1.8×1.8 mm2 LYSO arrays with lengths of 20 and 50 mm were constructed. Each pixelated crystal was fully and partially covered by enhanced specular reflector (ESR). To obtain the DOI responses, the long axis of crystal arrays were irradiated by electronically gamma rays from an F-18 radioactive source and the coincidence detector. The DOI positions with dual-ended readout were determined using energy-dispersion method. The DOI resolutions, energy resolutions, and PVRs of the detector configurations are obtained from 4.37 mm to 48.88 mm FWHM, 20.03 % to 28.47 % FWHM, and 4.84 to 12.15, respectively. The results show that the effects of crystal surface treatment and reflector covered area on DOI resolution, energy resolution and PVR performances are quite different in 20 mm- and 50 mm-long LYSO detectors. The unpolished, fully-reflector-covered detector configuration using 50 mm-long LYSO could be a suitable design for PGCI absorbers with depth-encoding capability, although this configuration design might degrade the PVR performance.


Nai-Yun Chang, Chih-Yi Ho, Tzung-Dau Wang, Wen-Jeng Lee and Chia-Yen Lee

Erectile dysfunction(ED) has been confirmed as one of the precursor of cardiovascular disease. The treatment and tracking of ED is one of the quite worth noting therapeutic indicators for patients with cardiovascular disease. At present, the medical team of National Taiwan University Hospital has pro-posed an innovative and effective therapy for ED. Simultaneously, experiments show that the three-dimensional pelvic vascular model can be established by using MSCT pelvic angiography images, which can be applied to the clinical diagnosis and tracking of ED patients. The software which purchased by the hospital can't accurately reconstruct the three-dimensional vascular model of the pelvic vascular, moreover the establishment of the vascular model requires the physician to perform complicated manual parameter adjustments, which is very time consuming and laborious. The MSCT pelvic vascular has the characteristics of complex HU value, low target segmentation vascular intensity, tiny blood vessels, multiple tortuosity, similar to surrounding soft tissues, lack of connectivity in the narrow segment. The above reasons make it difficult to segment accurately and quantify the vessels in pelvic vascular. So far, the current research can’t be applied to pelvic vascular reconstruction effectively. To assist physicians in clinical diagnosis and postoperative evaluation, this paper develops an automated pelvic vascular reconstruction and stenosis analysis algorithm. This paper develops a multi-scale modified Sato filter to calculate the vascular structural response value based on the Sato filter, increasing the vascular weight, and uses the adaptive parameter region growing method for vascular reconstruction. Utilize the resulting of pelvic vascular tree calculates simple path extraction, tube cross-sectional area quantification analysis and assessment of vascular stenosis based on the concept of graph theory. According to the branch calculation criteria given by the physicians, the average accuracy of the vessel segmentation result is 82%.