同步辐射在显微CT中的应用

计算机X射线断层成像技术（CT）是利用X射线的穿透能力对物体进行扫描,所得信号经过反投影的算法而得到物体二维分布的一种成像方法,已经在医学诊断、工业探伤等领域广泛应用。但是由于实验室光源的低通量,光源点大小及其单色性等限制了其向高分辨发展,通常其分辨率在0．5mm左右。利用微焦点X射线源作为光源的显微CT分辨率可以达到微米量级,但是由于其光通量低且为非单色光,对不同样品有不同程度的束线硬化,影响了其真实分辨率。同步辐射作为一种新兴的光源有高亮度、高光子通量、高准直性、高极化性、高相干性及宽的频谱范围的特点,配合高分辨的X射线探测器,可以发展同步辐射显微CT,其分辨率可达10μm以下。利用同步辐射的高空间相干性开展位相衬度显微CT的研究,对低吸收物质也可以清晰三维成像。新建的上海光源的X射线成像及生物医学应用线站开展了三维显微CT方面的研究,经过初步试验,得到了较好的结果。     

Spectroscopic imaging at compact inverse Compton X-ray sources

While K-edge subtraction (KES) imaging is a commonly applied technique at synchrotron sources, the application of this imaging method in clinical imaging is limited although results have shown its superiority to conventional clinical subtraction imaging. Over the past decades, compact synchrotron X-ray sources, based on inverse Compton scattering, have been developed to fill the gap between conventional X-ray tubes and synchrotron facilities. These so called inverse Compton sources (ICSs) provide a tunable, quasi-monochromatic X-ray beam in a laboratory setting with reduced spatial and financial requirements. This allows for the transfer of imaging techniques that have been limited to synchrotrons until now, like KES imaging, into a laboratory environment. This review article presents the first studies that have successfully performed KES at ICSs. These have shown that KES provides improved image quality in comparison to conventional X-ray imaging. The results indicate that medical imaging could benefit from monochromatic imaging and KES techniques. Currently, the clinical application of KES is limited by the low K-edge energy of available iodine contrast agents. However, several ICSs are under development or already in commissioning which will provide monochromatic X-ray beams with higher X-ray energies and will enable KES using high-Z elements as contrast media. With these developments, KES at an ICS has the ability to become an important tool in pre-clinical research and potentially advancing existing clinical imaging techniques.     

K-edge subtraction synchrotron X-ray imaging in bio-medical research

High contrast in X-ray medical imaging, while maintaining acceptable radiation dose levels to the patient, has long been a goal. One of the most promising methods is that of K-edge subtraction imaging. This technique, first advanced as long ago as 1953 by B. Jacobson, uses the large difference in the absorption coefficient of elements at energies above and below the K-edge. Two images, one taken above the edge and one below the edge, are subtracted leaving, ideally, only the image of the distribution of the target element. This paper reviews the development of the KES techniques and technology as applied to bio-medical imaging from the early low-power tube sources of X-rays to the latest high-power synchrotron sources. Applications to coronary angiography, functional lung imaging and bone growth are highlighted. A vision of possible imaging with new compact sources is presented.     

Functional lung imaging with synchrotron radiation: Methods and preclinical applications

Many lung disease processes are characterized by structural and functional heterogeneity that is not directly appreciable with traditional physiological measurements. Experimental methods and lung function modeling to study regional lung function are crucial for better understanding of disease mechanisms and for targeting treatment. Synchrotron radiation offers useful properties to this end: coherence, utilized in phase-contrast imaging, and high flux and a wide energy spectrum which allow the selection of very narrow energy bands of radiation, thus allowing imaging at very specific energies. K-edge subtraction imaging (KES) has thus been developed at synchrotrons for both human and small animal imaging. The unique properties of synchrotron radiation extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and also to map regional lung ventilation, perfusion, inflammation and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. This review summarizes synchrotron radiation imaging methods and overviews examples of its application in the study of disease mechanisms in preclinical animal models, as well as the potential for clinical translation both through the knowledge gained using these techniques and transfer of imaging technology to laboratory X-ray sources.     

A proof of principle experiment for microbeam radiation therapy at the Munich compact light source

Microbeam radiation therapy (MRT), a preclinical form of spatially fractionated radiotherapy, uses an array of microbeams of hard synchrotron X-ray radiation. Recently, compact synchrotron X-ray sources got more attention as they provide essential prerequisites for the translation of MRT into clinics while overcoming the limited access to synchrotron facilities. At the Munich compact light source (MuCLS), one of these novel compact X-ray facilities, a proof of principle experiment was conducted applying MRT to a xenograft tumor mouse model. First, subcutaneous tumors derived from the established squamous carcinoma cell line FaDu were irradiated at a conventional X-ray tube using broadbeam geometry to determine a suitable dose range for the tumor growth delay. For irradiations at the MuCLS, FaDu tumors were irradiated with broadbeam and microbeam irradiation at integral doses of either 3 Gy or 5 Gy and tumor growth delay was measured. Microbeams had a width of 50 µm and a center-to-center distance of 350 µm with peak doses of either 21 Gy or 35 Gy. A dose rate of up to 5 Gy/min was delivered to the tumor. Both doses and modalities delayed the tumor growth compared to a sham-irradiated tumor. The irradiated area and microbeam pattern were verified by staining of the DNA double-strand break marker γH2AX. This study demonstrates for the first time that MRT can be successfully performed in vivo at compact inverse Compton sources.     

Principles and applications of dual source CT

This article describes the technical principles and clinical applications of dual source CT. A dual source CT (DSCT) is a CT system with two x-ray tubes and two detectors at an angle of approximately 90°. Both measurement systems acquire CT scan data simultaneously at the same anatomical level of the patient (same z-position). DSCT provides temporal resolution of approximately a quarter of the gantry rotation time for cardiac, cardio-thoracic and pediatric imaging. Successful imaging of the heart and the coronary arteries at high and variable heart rates has been demonstrated. DSCT systems can be operated at twice the spiral pitch of single source CT systems (up to pitch 3.2). The resulting high table speed is beneficial for pediatric applications and fast CT angiographic scans, e. g. of the aorta or the extremities. Operating both X-ray tubes at different tube potential (kV) enables the acquisition of dual energy data and the corresponding applications such as monoenergetic imaging and computation of material maps. Spectral separation can be improved by different filtration of the X-ray beams of both X-ray tubes. As a downside, DSCT systems have to cope with some challenges, among them the limited size of the second measurement system, and cross-scattered radiation.     

Laboratory cryo soft X-ray microscopy

Lens-based water-window X-ray microscopy allows two- and three-dimensional (2D and 3D) imaging of intact unstained cells in their near-native state with unprecedented contrast and resolution. Cryofixation is essential to avoid radiation damage to the sample. Present cryo X-ray microscopes rely on synchrotron radiation sources, thereby limiting the accessibility for a wider community of biologists. In the present paper we demonstrate water-window cryo X-ray microscopy with a laboratory-source-based arrangement. The microscope relies on a λ=2.48-nm liquid-jet high-brightness laser-plasma source, normal-incidence multilayer condenser optics, 30-nm zone-plate optics, and a cryo sample chamber. We demonstrate 2D imaging of test patterns, and intact unstained yeast, protozoan parasites and mammalian cells. Overview 3D information is obtained by stereo imaging while complete 3D microscopy is provided by full tomographic reconstruction. The laboratory microscope image quality approaches that of the synchrotron microscopes, but with longer exposure times. The experimental image quality is analyzed from a numerical wave-propagation model of the imaging system and a path to reach synchrotron-like exposure times in laboratory microscopy is outlined.     

Visualizing the internal structure of polyethylene glycol-impregnated wood by digital breast tomosynthesis

This study proposes digital breast tomosynthesis (DBT) as a low-tube-voltage method for imaging wood artifacts treated with polyethylene glycol (PEG). In case of general clinical X-ray Computed Tomography (X-CT), PEG-impregnated wood images typically suffer from low contrast between the PEG and the tree-ring. Because X-CT uses high-tube-voltage X-rays that have high energy, they are transmitted regardless of the X-ray absorption difference of the substance, and therefore, it is not suitable for imaging PEG-impregnated wood. Mammography uses low-tube-voltage X-rays, and therefore, it is suitable for delineating substances with small X-ray absorption differences. However, although mammography can produce high-contrast images of wood, it cannot distinguish three-dimensional (3D) structures such as tree rings, because those are projection images. DBT is a type of mammography used to enhance contrast using low-tube voltage, and it enables imaging 3D structures by exposure X-rays to objects several times changing the exposure angle, and it can obtain quasi-computed tomography. Therefore, we believe that by applying DBT to dendroarchaeology, it would be possible to obtain high-contrast, high-resolution images in the visualization of the internal structure of wood.In this study, we used clinical X-CT, mammography, and DBT to obtain images of wood after PEG impregnation, and we evaluated the internal structure of the wood and the visibility of annual rings. We obtained DBT images as a tomogram with a thickness of 1 mm, which eliminated the distortion of tree rings in the sagittal direction and duplication of the PEG and the tree-ring. Further, tree-rings were easily visualized without a noticeable blur, and the DBT contrast was improved compared to clinical X-CT contrast because DBT was performed at low voltage. Important wooden artifacts excavated from ruins were preserved by PEG. Therefore, this method can be expected to become a very useful tool for dendroarchaeology when used as a complementary tool for microfocus X-CT.     

Iron nanoparticles from animal blood for cellular imaging and targeted delivery for cancer treatment

Background

Iron nanoparticles (INPs) are usually prepared from inorganic sources, but we have prepared it from goat blood using incineration method. These INPs are then coated with chitosan (C) and coupled with folic acid (F) to form bionanocomposite for folate receptors.

Methods

The bionanocomposite was characterized for its physicochemical properties and cancer cell targeting studies using Fourier transform infrared spectroscopy, transmission electron microscopy, Zeta potential analysis, scanning electron microscopy–energy dispersive X-ray spectroscopy and magnetic resonance imaging analyses.

Results

The results have shown that the particle size of the INP-CF was found to be 80–300 nm and confirmed the presence of chitosan and folic acid in the bionanocomposite. Cancer and normal mouse embryonic cell line study confirmed the internalization of INP-CF and this phenomenon was also supported by physicochemical studies.

Conclusion

Thus, nanobiocomposite prepared using natural sources as a raw material will be beneficial compared to commercially available synthetic sources and can be used as receptor targeting agent for cancer treatment. This nanobiocomposite when coupled with substances such as monoclonal antibodies might act as a theranostic nanoagent for cancer therapy in the years to come.

General significance

The prepared novel nanobiocomposite containing INPs isolated from natural source may be used as multifunctional agent due its paramagnetic property apart from its drug delivery effect.     

Potential of compact Compton sources in the medical field

The exceptional improvement of high power lasers and optical cavity finesses in the last fifteen years allows today the development of X-ray sources based on inverse Compton scattering. These compact sources will provide high intensity beams, with a tunable energy in the range 20–100 keV, that can be used in several application including material sciences, structural biology, cultural heritage research and preservation and medical or biomedical preclinical and clinical research. The access to these devices will be easier. Methods currently used only in synchrotron facilities will be available in dedicated work environment such as hospitals, laboratories or museums. Several machines are in design or construction phase, and aim at producing 10¹²–10¹⁴ ph/s. The ThomX machine is the most advanced project and has the potential to be used as the radiation source for biomedical searches, clinical imaging techniques or radiotherapy programs.     

Cryo X-ray microscope with flat sample geometry for correlative fluorescence and nanoscale tomographic imaging

X-ray imaging offers a new 3-D view into cells. With its ability to penetrate whole hydrated cells it is ideally suited for pairing fluorescence light microscopy and nanoscale X-ray tomography. In this paper, we describe the X-ray optical set-up and the design of the cryo full-field transmission X-ray microscope (TXM) at the electron storage ring BESSY II. Compared to previous TXM set-ups with zone plate condenser monochromator, the new X-ray optical layout employs an undulator source, a spherical grating monochromator and an elliptically shaped glass capillary mirror as condenser. This set-up improves the spectral resolution by an order of magnitude. Furthermore, the partially coherent object illumination improves the contrast transfer of the microscope compared to incoherent conditions. With the new TXM, cells grown on flat support grids can be tilted perpendicular to the optical axis without any geometrical restrictions by the previously required pinhole for the zone plate monochromator close to the sample plane. We also developed an incorporated fluorescence light microscope which permits to record fluorescence, bright field and DIC images of cryogenic cells inside the TXM. For TXM tomography, imaging with multi-keV X-rays is a straightforward approach to increase the depth of focus. Under these conditions phase contrast imaging is necessary. For soft X-rays with shrinking depth of focus towards 10nm spatial resolution, thin optical sections through a thick specimen might be obtained by deconvolution X-ray microscopy. As alternative 3-D X-ray imaging techniques, the confocal cryo-STXM and the dual beam cryo-FIB/STXM with photoelectron detection are proposed.     

Biological applications of synchrotron radiation infrared spectromicroscopy

Extremely brilliant infrared (IR) beams provided by synchrotron radiation sources are now routinely used in many facilities with available commercial spectrometers coupled to IR microscopes. Using these intense non-thermal sources, a brilliance two or three order of magnitude higher than a conventional source is achievable through small pinholes (< 10 μm) with a high signal to-noise ratio. IR spectroscopy is a powerful technique to investigate biological systems and offers many new imaging opportunities. The field of infrared biological imaging covers a wide range of fundamental issues and applied researches such as cell imaging or tissue imaging. Molecular maps with a spatial resolution down to the diffraction limit may be now obtained with a synchrotron radiation IR source also on thick samples. Moreover, changes of the protein structure are detectable in an IR spectrum and cellular molecular markers can be identified and used to recognize a pathological status of a tissue. Molecular structure and functions are strongly correlated and this aspect is particularly relevant for imaging. We will show that the brilliance of synchrotron radiation IR sources may enhance the sensitivity of a molecular signal obtained from small biosamples, e.g., a single cell, containing extremely small amounts of organic matter. We will also show that SR IR sources allow to study chemical composition and to identify the distribution of organic molecules in cells at submicron resolution is possible with a high signal-to-noise ratio. Moreover, the recent availability of two-dimensional IR detectors promises to push forward imaging capabilities in the time domain. Indeed, with a high current synchrotron radiation facility and a Focal Plane Array the chemical imaging of individual cells can be obtained in a few minutes. Within this framework important results are expected in the next years using synchrotron radiation and Free Electron Laser (FEL) sources for spectro-microscopy and spectral-imaging, alone or in combination with Scanning Near-field Optical Microscopy methods to study the molecular composition and dynamic changes in samples of biomedical interest at micrometric and submicrometric scales, respectively.     

Application of MOSFET detectors for dosimetry in small animal radiography using short exposure times

Digital subtraction angiography (DSA) X-ray imaging for small animals can be used for functional phenotyping given its ability to capture rapid physiological changes at high spatial and temporal resolution. The higher temporal and spatial requirements for small-animal imaging drive the need for short, high-flux X-ray pulses. However, high doses of ionizing radiation can affect the physiology. The purpose of this study was to verify and apply metal oxide semiconductor field effect transistor (MOSFET) technology to dosimetry for small-animal diagnostic imaging. A tungsten anode X-ray source was used to expose a tissue-equivalent mouse phantom. Dose measurements were made on the phantom surface and interior. The MOSFETs were verified with thermoluminescence dosimeters (TLDs). Bland-Altman analysis showed that the MOSFET results agreed with the TLD results (bias, 0.0625). Using typical small animal DSA scan parameters, the dose ranged from 0.7 to 2.2 cGy. Application of the MOSFETs in the small animal environment provided two main benefits: (1) the availability of results in near real-time instead of the hours needed for TLD processes and (2) the ability to support multiple exposures with different X-ray techniques (various of kVp, mA and ms) using the same MOSFET. This MOSFET technology has proven to be a fast, reliable small animal dosimetry method for DSA imaging and is a good system for dose monitoring for serial and gene expression studies.     

Imaging Liver Lesions Using Grating-Based Phase-Contrast Computed Tomography with Bi-Lateral Filter Post-Processing

X-ray phase-contrast imaging shows improved soft-tissue contrast compared to standard absorption-based X-ray imaging. Especially the grating-based method seems to be one promising candidate for clinical implementation due to its extendibility to standard laboratory X-ray sources. Therefore the purpose of our study was to evaluate the potential of grating-based phase-contrast computed tomography in combination with a novel bi-lateral denoising method for imaging of focal liver lesions in an ex vivo feasibility study. Our study shows that grating-based phase-contrast CT (PCCT) significantly increases the soft-tissue contrast in the ex vivo liver specimens. Combining the information of both signals – absorption and phase-contrast – the bi-lateral filtering leads to an improvement of lesion detectability and higher contrast-to-noise ratios. The normal and the pathological tissue can be clearly delineated and even internal structures of the pathological tissue can be visualized, being invisible in the absorption-based CT alone. Histopathology confirmed the presence of the corresponding findings in the analyzed tissue. The results give strong evidence for a sufficiently high contrast for different liver lesions using non-contrast-enhanced PCCT. Thus, ex vivo imaging of liver lesions is possible with a polychromatic X-ray source and at a spatial resolution of ∼100 µm. The post-processing with the novel bi-lateral denoising method improves the image quality by combining the information from the absorption and the phase-contrast images.     

CZT gamma camera for scintimammography

A high performance prototype gamma camera based on the semiconductor radiation detector Cd(Zn)Te is described. The camera features high spatial resolution, high-energy resolution, a reduced dead space on the edge of the field of view, and a compact format. The camera performance was first examined by comparison of small field of view examinations with those from an Elscint SP6HR standard clinical gamma camera. The new camera was found to give equal or improved image quality. The camera was then used for a systematic phantom study of small lesions in a background as would be found in breast cancer imaging. In this study the camera was able to systematically detect smaller, deeper, and fainter lesions. The camera is presently being used in a clinical trial aimed to assess its value in scintimammography where previous limitations of image quality and detector size have restricted the use of the functional imaging techniques. Preliminary results from 40 patients show high sensitivity and specificity with respect to X-ray mammography and surgery.     

Lead sulfide near-infrared quantum dot bioconjugates for targeted molecular imaging

In this paper, we report the use of lead sulfide quantum dot (PbS QD) bioconjugates as near infrared (NIR) contrast agents for targeted molecular imaging with expanded emission wavelengths beyond 1000 nm. The red-shifted emission band, coupled with the small particle size, which will facilitate clearance, both afford PbS QDs unique properties for noninvasive, high resolution in vivo NIR imaging applications. We have performed imaging experiments at the molecular level using surface-modified PbS NIR QDs, together with our lab-built NIR imaging system. This novel instrumentation and fluorescent contrast agent have enabled us to study the relatively unexplored NIR biomedical imaging spectral region of 900-1200 nm. Preliminary experimental results indicate that PbS-QD/antibody bioconjugates are promising candidates for targeted NIR molecular imaging and future in vivo NIR tissue imaging applications.     

Scanning Microfocus Small Angle X-ray Scattering Study of the Avian Eggshell

Synchrotron microfocus small angle X-ray scattering was used to investigate the nanostructure and microscopic variation of eggshells. It uses a microbeam allowing the ability to probe interactions between the organic and inorganic components at nanometer level and is ideal for mapping over small areas to obtain a detailed analysis of structural variations. Thin sections of eggshells were scanned from the shell membrane （inner） to the cuticle （outer） surface. The data collected was used to produce two-dimensional maps showing microscopic changes within the different layers of the eggshell. The structural alterations ap- parently could have implications at the macroscopic level of the resulting eggshell. As the organic matrix is embedded within the eggshell this may contribute to the variations observed in calcite crystal form and texture, Structural information obtained about a biomaterial at different length scales is important in relating the structure to its functional properties. This knowledge and the principles behind the formation of biomaterials could be used in the attempt of bioengineering new systems.     

Broadband Mid-Infrared Super-Resolution Imaging with Metallic Nanorod-Bridged Dimer Array

We propose a broadband mid-infrared super-resolution imaging system comprising a metallic nanorod-bridged dimer array. The imaging array enables super-resolution imaging of shaped dipole sources in the near field. A charge transfer plasmon (CTP) appears in a metallic nanorod-bridged dimer. By varying the radius of the junction, the plasmon resonance wavelength of CTP mode can be tuned into the mid-infrared region. Here, we investigate the broadband super-resolution imaging of the incoherent and coherent dipole sources at mid-infrared wavelengths. With the array pitch varying, we calculate the cross-sectional field intensity distributions at the source plane and the image plane by using the finite element method. The simulation results indicate that the broadband incoherent and coherent super-resolution imaging can be realized at mid-infrared wavelengths with the imaging array. The image quality is sensitively dependent on the source coherent, the array pitch, and the distance from the image plane to the array. In the same structural parameters, the image quality of coherent source of in-phase is lower than that of incoherent source. Increasing the array pitch improves the image quality but it also increases the size of the array. By reasonably choosing the array pitch of the array, the spatial resolution of ～λ/109 and ～λ/73 is obtained corresponding to the incoherent imaging case and coherent imaging case at the mid-infrared wavelength of 4390 nm. Moreover, the larger image-array distance results in the lower image quality.     

Hybrid framework for feasible modeling of an edge illumination X-ray phase-contrast imaging system at a human scale

Here, we present a hybrid approach for simulating an edge illumination X-ray phase-contrast imaging (EIXPCi) set-up using graphics processor units (GPU) with a high degree of accuracy. In this study, the applicability of pixel, mesh and non-uniform rational B-splines (NURBS) objects to carry out realistic maps of X-ray phase-contrast distribution at a human scale is accounted for by using numerical anthropomorphic phantoms and a very fast and robust simulation framework which integrates total interaction probabilities along selected X-ray paths. We exploit the mathematical and algorithmic properties of NURBS and describe how to represent human scale phantoms in an edge illumination X-ray phase-contrast model. The presented implementation allows the modeling of a variety of physical interactions of x-rays with different mathematically described objects and the recording of quantities, e.g. path integrals, interaction sites and deposited energies. Furthermore, our efficient, scalable and optimized hybrid Monte Carlo and ray-tracing projector can be used in iterative reconstruction algorithms on multi GPU heterogeneous systems. The preliminary results of our innovative approach show the fine performance of an edge illumination X-ray phase-contrast medical imaging system on various human-like soft tissues with noticeably reduced computation time. Our approach to the EIXPCi modeling confirms that building a true imaging system at a human scale should be possible and the simulations presented here aim at its future development.     

CdTe compact gamma camera for coded aperture imaging in radioguided surgery

The aim of this work was to assess the performance of a prototype compact gamma camera (MediPROBE) based on a CdTe semiconductor hybrid pixel detector, for coded aperture imaging. This probe can be adopted for various tasks in nuclear medicine such as preoperative sentinel lymph node localization, breast imaging with ^99mTc radiotracers and thyroid imaging, and in general in radioguided surgery tasks. The hybrid detector is an assembly of a 1-mm thick CdTe semiconductor detector bump-bonded to a photon-counting CMOS readout circuit of the Medipix2 series or energy-sensitive Timepix detector. MediPROBE was equipped with a set of two coded aperture masks with 0.07-mm or 0.08-mm diameter holes. We performed laboratory measurements of field of view, system spatial resolution, and signal-difference-to-noise ratio, by using gamma-emitting radioactive sources (¹⁰⁹Cd, ¹²⁵I, ²⁴¹Am, ^99mTc). The system spatial resolution in the lateral direction was 0.56 mm FWHM (coded aperture mask with holes of 0.08 mm and a 60 keV source) at a source-collimator distance of 50 mm and a field of view of 40 mm by side. Correspondingly, the longitudinal resolution in 3D source localization tasks was about 3 mm. MediPROBE showed a significant improvement in terms of spatial resolution when equipped with the high-resolution coded apertures, with respect to the performance previously reported with 1–2 mm pinhole apertures as well as with respect to adopting a 0.35 mm pinhole aperture.