Core Laboratory

CORE LABORATORY

In order to successfully carry out the research projects mentioned above, we plan to establish 6 core facilities to provide technical platforms for all research teams in HARC.

	Metabolomic Core

	Metabolomics is a newly emerging field concerned with the comprehensive characterization of low-molecular-weight (LMW) metabolites in biological systems. Information obtained from metabolomics approach may provide a global view of the metabolic pathways, network, and their interactions in normal and pathophysiological states. Accordingly, metabolomics-based information may help to detect disease progression, monitor response to treatment, and identify new targets for drug design. Since a global, unbiased approach is undertaken, metabolomics is most applicable to human degenerative diseases including diabetes, cardiovascular disease, and neurodegenerative diseases, which involve the interactions of multiple risk factors in disease pathogenesis and progression. Metabolomics approach relies on nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) as the key tools for untargeted metabolite profiling and target metabolite identification. Plasma, urine, CSF, cells and biospecimens are samples for analysis. Precise determination of metabolite concentration is not always necessary in an early stage. If specific metabolites (target metabolites) turn out to be important, the information of their concentrations becomes instructive.



	Biomedical Imaging Core

	The Biomedical Imaging Core will support research projects that utilize imaging modalities in human and animals. Core members, including faculties of Department of Medical Imaging and Radiological Sciences (MIRS) and Department of Electrical Engineering (EE) of Chang Gung University (CGU), will assist the development of imaging protocols and coordinate and the image acquisition using modalities in the Department of Medical Imaging and Intervention, the Department of Nuclear Medicine and the Molecular Imaging Center (MIC) of the Chang Gung Memorial Hospital (CGMH). Human imaging modalities that may be useful for the Research Center For Gerontology include magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single photon emission computed tomography (SPECT), ultrasound and angiography systems. Animal imaging modalities include MRI, CT, microPET, nanoSPECT/CT and others in the MIC. Radiopharmaceutical facilities in both MIRS of CGU and MIC of CGMH may be used to produce tracers for nuclear medicine imaging in human and animals. Imaging processing and display facilities will be established at CGU and supported by EE and MIRS members to satisfy the needs from all the related research projects. Core members will also develop novel biomedical imaging acquisition and processing methods as well as implement start-of-the-art techniques for researches in gerontology. The followings provide brief descriptions of the basic specification and capability of each modality or unit related to the Core: Human and Animal MRI 3T clinical MRI scanners will be used for imaging patients and human volunteers. Anatomical and functional information can be obtained from different types of scans of the brain and body. They include lesion detection, local volume measurement and morphometric analysis from the anatomical scans, neural fiber integrity from diffusion tensor imaging, tissue blood flow and vessel density from the perfusion scan, functional connectivity from resting-state neural functional MRI (fMRI) and task-induced brain activation from task fMRI. Most of them can be quantified as indices for the purposes of diagnosis and evaluation of treatment response. The spatial resolution can reach approximately 0.5 mm for the anatomical scans and 2 mm for the functional scans. A 7T animal MRI scanner with 30-cm bore size will be used for small animal imaging (including rats and mice). Same information as from the above-mentioned human scans may be obtained in vivo. The spatial resolution can reach approximately 50 mm for the anatomical scans and 200 mm for the functional scans. Human and Animal CT A 320-row CT scanner with 16-cm coverage will be used for imaging patients and human volunteers. A 0.5-mm isotropic resolution can be reached with a speed of 0.3 s for imaging any parts of the body. These features are particular valuable for evaluation of coronary artery and heart imaging. The micro CT system is a major imaging modality in small animal experiments for translational researches. High spatial resolution at the order of 1 mm and high contrast images can be obtained. Applications of micro CT in small animals include anatomical imaging of bone and vascular network. Osteoporosis related problems have been a major aging related topic in humans. In small animal models, micro CT provides detail quantitative analysis for morphological assessment in tibia bones and bone regeneration with scaffolds in tissue engineering. Various indices and quantities such as bone mineral density and dimensional fractal can be calculated. Human PET/CT and Animal PET A Siemens Biograph TruePoint PET/CT scanner with capability to acquire time-of-flight (TOF) data will be used for imaging human subjects. The PET components have a 21.8 cm axial field-of-view with a 70 cm patient port. The measured system TOF resolution is less than 600 ps and the acquired list mode data provide the possibility for dynamic study. An animal microPET system (Inveon PET, Siemens) with 10×12cm FOV made of LSO crystals will be used for animal studies. The spatial resolution is 1.2 mm in the CFOV, and with list-mode and 3D data acquisition capability for dynamic study as well as transmission source for attenuation and scatter corrections. Human SPECT and Animal SPECT/CT A Siemens e.cam dual-head gamma camera will be used for imaging human subjects. The scanner has Flash 3D reconstruction technology available for optimizing acquisition time and image quality. The dual-head detectors allows for 180, 90 and 76 detector angle configurations to optimize image quality for whole body, cardiac and general SPECT study. The scanner also equipped multiple-line source array to produce a profiled transmission source shape, effectively correcting myocardial perfusion SPECT studies for non-uniform attenuation from organs surrounding the heart. A high-resolution NanoSPECT/CT (Bioscan Inc. USA), including a multi-pinhole SPECT, and CT will be used for the animal study. The multipinhole SPECT system is equipped with exchangeable aperture plates for both mice and rats. For the mouse apertures plates, there are 1.0 mm and 1.5 mm multi-pinholes with spatial resolutions of 0.8mm and 1.0 mm, respectively. For the rat apertures plates, there are 2.5 mm multi-pinholes with spatial resolutions of 1.6mm. Dynamic and dual tracer studies are available with special collimators. Ultrasound Two advanced ultrasonic imaging devices (Aplio XV and Nemio, Toshiba) are available for real-time B-mode sonography of the abdomen, pelvis and small parts. Each of these ultrasonic systems has at least two array transducers/probes with ultrasound frequencies ranging from 2 MHz to 9 MHz. These different probes are able to delineate the anatomical structures and abnormalities over the superficial part, small part, deeper structures and abdominal viscera. Moreover, the facilities also have the Doppler imaging mode (color Doppler scan and power Doppler scan) to evaluate not only the anatomic structures but also the haemodynamics of blood vessels. Angiography There are two state-of-art angiographic systems (Bransist Safire VF17, Shimadzu) that were recently installed. These systems are floor-mounted digital angiography systems. A 17x17-inch direct-conversion flat-panel detector (amorphous selenium, a-Se) is equipped as standard acquisition device, and a high heat capacity X-ray tube of 3.0 MHU is used for clinical angiography. The advanced imaging techniques, including DSA (digital subtracted angiography), RSM-DSA and CT-like, provide unique and outstanding functionalities in both clinical and research applications for the evaluation of the cardiovascular system. Radiotracers The radiochemistry facility of the core will prepare a variety of radiotracers to support the imaging studies with PET and SPECT. With the supply of positron emitters from the cyclotron facility (Sumitomo HM-12S) at CGMH, we will provide N-13-ammonia (for imaging myocardial perfusion), C-11-acetate (for imaging myocardial oxidative metabolism), F-18-FDG (for imaging myocardial glucose metabolism), F-18-AV-45 (for imaging b-amyloid plaques in the brain of Alzheimer’s disease patients and animal model), and F-18-AV-133 (for mapping the vesicular monoamine transporters subtype 2 in CNS and the pancreas). These tracers for PET studies in human will be prepared in accordance with the current good manufacturing practice (CGMP) guidance. Other radiotracers (such as F-18-FEBM for imaging serotonin transporters in CNS, and I-123-labeled tracers for imaging sigma receptors in CNS and the pancreas) will be supplemented by the radiochemistry laboratory at MIRS of CGU. Image Processing and Display The facility will contain high-performance PC workstations and up-to-date image processing software systems for medical image processing, storage, data analysis and image display. Hardware and software will be established to ensure high-speed calculation and handling of large array image data, such as 4-dimentional high-resolution images. The main processing functions will include image segmentation, image registration and fusion from different image modalities, 3D visualization, functional imaging analysis, image quantifications, statistical parametric mapping, and pharmacokinetic modeling for tracer studies.



	Physical Indices Assessment Core

	Human and Animal MRI To create “Physiologic Aging” markers for improvingperformances in animal study and clinical human trials, further establishing the integrated research platform. To develop “Functional Aging” markers for systematically evaluating aging-related decline of physical function, further applying more precision and efficiency in medical decisions. To integrated analyze and construct “Models of Aging Indices” by multimodal information fusion, further designing novel wearable device for the elderly. To establish “Robot-Assisted Therapy” that represents an interactive motion technology applied in elderly populations.



	Cognitive & Social Behavior Assessment Core

	This core lab coordinates research support and training for group projects regarding the cognitive and behavioral indices of aging in both health and in illness, for a neurodegenerative disease and for other projects measuring the cognitive and behavioral aspects of human as well as animals. This lab interfaces with our university's existing core facilities to develop research, educational and clinical programs that support and expand research in aging. The goal of the Cognitive & Social Behavior Assessment Core (CSBAC) program is to provide support and to enhance involvement and collaboration among researchers and faculty members at our university's 3 colleges, and to expand the interdisciplinary research in gerontology through the collaboration between investigators in aging research at Chang Gung University and the Chang Gung Memorial Hospitals. The mission of the CSBAC is to create, facilitate and expand interdisciplinary collaboration among investigators to further the academic excellence in the cognitive and behavioral aspects of clinical, epidemiological, basic-biomedical, mental health, legal-ethical, health services and population-based research on aging. Doing so will amplify and enrich these areas of research on aging, provide outstanding research training and educational opportunities to students, trainees and health professionals, and enhance the delivery of multi-disciplinary geriatric care to the elderly. The mouse behavioral phenotyping center will provide a set of behavioral monitoring equipments in order to establish a standard platform to globally screen genetically engineered mice or other disease models. The center equipments, along with analyses from animal imaging center and metabolomic center will grant a thorough phenotype investigation and strengthen the research in-depth. There are two separate parts to this CSBAC: the Human Cognitive and Behavioral Core and the Animal Cognitive and Behavioral core. The Human Cognitive and Behavioral Core consists of 3 parts: 1) magnetic navigated brain stimulator to improve the prognosis of stroke patients, 2) cognitive and behavioral measurement and analysis component to provide support for obtaining and developing measurements for cognitive and behavioral aspects of older adults and to provide assistance with measurement model testing, trajectory clustering and modeling., and 3) bio-behavioral assessment component to provide support for assessing and quantifying human activity and energy level.



	Intelligent Healthcare Devices Core

	This lab will establish the non-invasive physical detectors and the health care service network. This lab will also build up qualitative and quantitative database for healthy elders and elders with degenerative diseases, and these data could serve as a platform for future research.



	Three-dimensional Anthropometric Database and Welfare Design Core

	The core laboratory will provide methodological support for study cohort construction and anthropometric measurement, as well as offer both hardware and software for data management and statistical analysis. The key features are (a) establishment of community study and health examination data warehouse: with the adoption of methods from epidemiological design and biospeciman/questionnaire management, this core laboratory will help to explore prognostic/diagnostic markers for diseases associated with aging; (b) 3D whole body scanning and 3D whole body scanning and establishment of 3D human body surface measurement data bank: the core laboratory will assist in collection of human body feature data, biophysiological indicators, cognitive and behavioral measures, and health/medical history of the elders; (c) provision of digitalized manikins and simulation systems for assessment of the safety and health efficacy of wellbeing products under simulated environment; (d) Wellbeing design and applicability assessment: R&D and designs for health care and wellbeing products feasible to aging population. This core laboratory interfaces with our University's existing core facilities to develop research, clinical application and practical design that support and expand research in aging. 3D whole body scanning, which provides a detailed body shape, has been proposed as a sophisticated tool for accurately measuring obesity status, allowing for the identification of those most at risk of metabolic syndrome (MetS), hypertension, Type 2 diabetes, and cardiovascular diseases (CVD). Body surface dimensions should not therefore be regarded as a primitive approach for describing fat distribution, rather that 3D body scanning has a potential major role to play in both epidemiological studies of risk of the MetS, and the monitoring of individual subjects in response to intervention. Digital human model (DHM) simulation systems have been utilized as an effective design tool to visualize the interaction of a human and artifact system and to evaluate the human-artifact interaction from ergonomic aspects. The wellbeing design methodology using DHM makes the iterative process of design evaluation, diagnosis and revision more rapid and economical. The research team has published dozens of international journal papers in the related fields during the past few years. The core laboratory derived from epidemiological studies will be useful for future researches in gerontology and molecular medicine. The cross validations of biomarkers from basic medicine to epidemiological studies will further the researches in etiology, prognosis, and nature history of major diseases. Health examination data bank provides support for biomarkers of aging in MetS and CVD. 3D surface anthropometric data bank provide support for physical indices of aging, cognitive & behavior indices of aging, social & economical indices of aging, and improvement of aging indices by herbal medicine. A DHM simulation system has been used as an effective tool for wellbeing design and evaluation of products and workplaces in virtual environment. The DHM generation method proposed in the present study is of use to efficiently generate a group of DHM representing the elderly population. DHM simulation system & usability assessment provide support for physical, cognitive & behavior, social & economical, and herbal medicine related wellbeing devices/services design study.

Metabolomics Core Laboratory

Biomedical Imaging Core Laboratory