Imaging System For Medical Applications Research Articles

High-Content Analysis of Single Cells Using a Wide-Field Imaging Sensor

Introduction Single cell analysis can highlight the heterogeneity of individual cells that conventional bulk analysis cannot address, and thus has attracted much attention from a broad range of scientific fields. A number of techniques have emerged in order to separate, array, and detect single cells, however, conventional microscopy is an almost only choice to visualize biological phenomena in single cells. There is no doubt that microscopy is a powerful tool for the single cell analysis, while the inherent low throughput hampers the analysis of very rare cells or biological events. To address this issue, we have proposed a high-content analysis based on a wide-field imaging sensor that visualizes the area of several mm2 in one-shot. Since a complementary metal oxide semiconductor (CMOS) image sensor is employed as a detector, a space-saving and inexpensive platform can be designed. By taking these advantages, we have demonstrated a variety of cell analyses. In this presentation, after introducing the basic principle of our imaging sensor, detection of single cells for human immunodeficiency virus (HIV) testing and tumor evaluation, and microbial identification by lens-less imaging of microcolonies will be introduced. CD4 testing with a wide-field imaging sensor for detection of HIV infection Approximately 35 million people world-wide carry HIV, which causes acquired immune deficiency syndrome (AIDS). Because HIV infection causes decrease in T-cells expressing cluster of differentiation (CD) antigen, CD4, the number of CD4-positive T-cells in patient blood samples is a useful indicator of therapeutic effect of the antiviral treatment. Flow cytometry is used for this CD4 testing, however its high cost, lack of portability and difficulty in operation limit widespread use in resource-limited areas. To overcome this limitation, wide-field imaging sensor-based CD4 testing was developed with the aid of a cell arraying device (referred to as microcavity array) on which single T-cells can be trapped and arrayed. Immuno-stained CD4-positive T-cells on the microcavity array were visualized by the sensor, indicating the usefulness of this imaging system for medical applications. Detection of circulating tumor cells with a wide-field imaging sensor Circulating tumor cells (CTC) are tumor cells circulating in peripheral blood, and involved in metastasis. Since CTCs provide useful information such as malignancy and metastatic property of primary tumor, development of fundamental techniques for recovery, counting and analysis of CTCs is important for clinical purposes. We have developed a CTC-recovery technology using microcavity array by which very rare CTCs in blood can be captured. For subsequent analysis, we combined the microcavity array system with a wide-field imaging sensor, so that efficient recovery and detailed observation of rare CTCs can be performed in all-in-one system. Furthermore genome analysis of single cells captured on the microcavity array will be also discussed in the presentation. Microbial identification based on lens-less imaging of microcolonies with a wide-field imaging sensor Identification of microbial species is routinely performed in a wide range of industries, including production of beverages, foods, cosmetics and pharmaceuticals. It is also of great importance in clinical diagnosis. A number of methods based on phenotypic and genotypic analyses have been proposed for microbial identification, however such methods need expensive reagents and long assay time. Rather than analyzing chemical components (e.g., DNA, proteins and lipids) of the detected microbes, observation of colony morphology has long been employed to identify microbial species although it requires high expertise. We deskilled the colony morphology-based microbial identification by observing microcolonies with a wide-field imaging sensor which are free from optical lens systems (lens-less imaging). Microcolony growth was monitored with high time-resolution, and various parameters were extracted from the acquired images. Based on the cluster analysis, we succeeded in identification of microbial species with high accuracy.

Terahertz Imaging System for Medical Applications and Related High Efficiency Terahertz Devices

A terahertz (THz) imaging system and high efficient terahertz sources and detectors for medical applications were developed. A fiber laser based compact time domain terahertz tomography system was developed with a high depth resolution of less than 20 μm. Three-dimensional images of porcine skin were obtained including some physical properties such as applied skin creams. The discrimination between healthy human tissue and tumor tissue has been achieved using reflection spectra.

TH-A-141-07: Characterization of X-Ray Source and Detector Geometry for the Compton Backscatter Imaging System for Medical Applications

Purpose: Clinical applicability of Compton backscatter imaging (CBI) systems for medical purposes was previously demonstrated using a CBI system optimized for industrial purposes. In order to optimize CBI for medical imaging, two key CBI system parameters were characterized: 1) x‐ray source and 2) detector geometry. This data can be used to help design systems with optimal spatial resolution, subject contrast, and SNR across clinical imaging applications. Methods: Phantoms of different dimensions and compositions, as well as segmented detectors, were simulated using MCNP‐X, a Monte Carlo transport code. With each set of simulations, a different energy between 20 keV and 1.5 MeV was evaluated. To maximize the potential of MCNP‐X, multiple in‐house C++ and MATLAB algorithms were created to extract and evaluate relevant data from the plethora of MCNP‐X generated information. An analytical model of the system was created to verify the Monte Carlo results. Results: The best subject contrast was observed at lower incident energies, between 30 and 40 keV, and also for smaller detectors. The SNR peaked at higher energies, between 65 and 75 keV, and at detector pixels adjacent to the source. As expected, the penetration power of the beam increased with energy. The spatial resolution of the system became worse (larger PSF) as the size of the detector increased. The absorbed doses to the phantom, per starting particle, increased with the energy, but were either equivalent to or lower than doses observed in transmission imaging at energies of interest. Conclusion: As part of the optimization of a medical CBI system, potential for better images was shown. The ability to design optimal medical CBI systems with x‐ray tubes within diagnostic energy ranges and detectors compatible with diagnostic spatial constraints was demonstrated. CBI can provide single‐sided imaging capability with equivalent or lower absorbed dose.

A high-resolution three-dimensional far-infrared thermal and true-color imaging system for medical applications

As the needs for various kinds of body surface information are wide-ranging, we developed an imaging-sensor integrated system that can synchronously acquire high-resolution three-dimensional (3D) far-infrared (FIR) thermal and true-color images of the body surface. The proposed system integrates one FIR camera and one color camera with a 3D structured light binocular profilometer. To eliminate the emotion disturbance of the inspector caused by the intensive light projection directly into the eye from the LCD projector, we have developed a gray encoding strategy based on the optimum fringe projection layout. A self-heated checkerboard has been employed to perform the calibration of different types of cameras. Then, we have calibrated the structured light emitted by the LCD projector, which is based on the stereo-vision idea and the least-squares quadric surface-fitting algorithm. Afterwards, the precise 3D surface can fuse with undistorted thermal and color images. To enhance medical applications, the region-of-interest (ROI) in the temperature or color image representing the surface area of clinical interest can be located in the corresponding position in the other images through coordinate system transformation. System evaluation demonstrated a mapping error between FIR and visual images of three pixels or less. Experiments show that this work is significantly useful in certain disease diagnoses.

Development of a multi-spectral imaging system for medical applications

We describe the development of a multi-spectral imaging (MSI) system based on a rapid-scanning solid-state device, an acousto-optic tunable filter (AOTF), for wavelength selection and a two-dimensional charge-coupled device for detection. The MSI device is designed for in vivo optical detection in medical diagnostic applications. Unlike conventional grating spectrometers, the AOTF is a miniature solid-state device that has no moving parts, and can be rapidly tuned to any wavelength within its operating range. The large aperture of the AOTF and its high spatial resolution allows the optical image from an imaging fibre optic probe to be recorded by the detector. These characteristics, combined with their small size, make AOTFs important new alternatives to conventional monochromators, especially for spectral imaging in biomedical applications. The MSI can also be used for dual-modality diagnostics to detect both fluorescence and diffuse reflectance images. The usefulness and potential of the MSI system is illustrated in several applications of biomedical interest, such as reflectance fluorescence imaging of skin and brain tissues.