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Synchrotron Radiation X-ray Imaging And Spectroscopy Of Tumor Tissues

Posted on:2007-10-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:C L LiuFull Text:PDF
GTID:1104360212484654Subject:Condensed matter physics
Abstract/Summary:PDF Full Text Request
The cancer is one of the illnesses seriously harming human health and lift. At the present time, conventional clinic diagnoses of cancer are mainly the histopathology, imaging and so on. At recent years, many kinds of new diagnosing techniques are continually developed, and make the diagnosis of cancer to its early stage, more exact and precise or no hurting. In this paper, the X-ray imaging and several spectroscopy techniques based on synchrotron radiation are used to study the micro-structures of various breast tissues and uterine leiomyomas. The importance of these methods in distinguishing the normal, benign or cancerous tissues is evaluated, and the basis for medical applications of synchrotron radiation is also discussed.At first, the microstructures of breast tumors and uterine leiomyomas are studied by the X-ray imaging, such as diffraction enhanced imaging (DEI). On the basis of the DEI's principle, the processes and character of DEI are analyzed by a simple experimental model. The key point of the DEI setup is the analyzer which is a perfect crystal. X-rays from the synchrotron light source pass through a monochromator and are translated into monoenergetic lights. The monoenergetic X-rays traverse a sample and undergo diffraction by the analyzer crystal, and are finally recorded by the detector. When the X-rays traverse the sample, they are refracted by very small angles (around microradians) due to the tiny variation of refractive indexes in the sample. The analyzer crystal can almost eliminate the X-rays scattered within a large angle by the sample. The X-rays emerging from the sample and hitting the analyzer crystal will satisfy the conditions for Bragg diffraction only for a very narrow range of incident angles (typically on the order of a few microradians). If the X-rays that have been refracted by the sample are within the angular acceptance range of the analyzer, they will be diffracted to the detector. Otherwise, if the X-rays that have been scattered by the sample will fall outside this angular acceptance range, they will not be reflected at all. The relationship of reflectivity on incident angle is called rocking curve. The rocking curve is usually a triangular-shaped one whose full width of half maximum (FWHM) is about several microradians. Since the resulting refraction contrast originates from the slope of either shoulder of the triangular-shaped rocking curve, it depends on its FWHM as well as the tuning angle. We can obtain various images at different positions of rocking curve with tuning the analyzer crystal. These pictures contain the absorption, therefraction and the extinction (that is to say, the small angle scattering is rejected) information. In the DEI experiment, three kinds of images can be obtained. One is recoded at the peak of rocking curve, which is usually called diffraction image because the analyzer is in Bragg angle position, the diffraction images have higher contrast than the absorption images and can show also micro-structures inside the breast tissues. Other two images can be obtained when the analyzer is tuned to the FWHM positions on either side of the rocking curve. These two images contain the same absorption information but the opposite refraction information. Consequently the different information from two images can be separated through pixel-by-pixel algorithm. When two images are added, we can obtain the apparent absorption image that has only absorption, no refraction effect, but with weak extinction. The apparent absorption image is similar to the conventional X-ray image. When two images are subtracted, we can obtain the refraction image in which the edge effect has been enhanced. The refraction image is extraordinarily sensitive to the change of the refractive index of the sample, and can clearly display edges of organic tissues having different refractive indexes. Furthermore, the background of the analyzer crystal shall affect the quality of the imaging, but does not affect the refraction image. There is aesthetically consistent relationship between the object and the refraction image. So, the refraction image has very good reliability in distinguishing normal or disease tissues, as well as for industry examining.We have also recorded the images by X-ray films and read by an optical microscope. In this case two different methods were used. One of them is to place the X-ray film about 1 cm behind the sample and no analyzer crystal will be used, then to record the image called absorption image, resembling the conventional mammography. For the another method the X-ray film is just placed behind the analyzer crystal which is in the top position of its rocking curve, then the so called diffraction images are obtained. These images can display more abundant microstructures of various tissues when they are read by the optical microscope, but its imaging process is not as convenient as use of CCD.The changes of rocking curves are also carefully studied as various breast tissues are inserted. The differences of the integrated intensity of rocking curves are also possible to distinguish the normal, benign or malignant breast tissues.The relations between the contrast of different DEI images and the X-ray energies are discussed. The results show that the contrasts of diffraction image or apparent absorption image keep unchanged when different X-ray energies are used. The contrast of refraction image trends to be weakened when the X-ray energy is increased. As a result, it seems the DEI method fits for imaging light elements.The uterine leiomyomas are imaged using synchrotron radiation. The results show the optical microscope can only observe the surface morphology of the sample, but not the inner structures. The DEI images can clearly show inside micro-structures of uterine leiomyomas, including the burble structure, hyaline degeneration and rupture of muscle fibers, red degeneration and cavum of myomatous in the inner of uterine leiomyomas. The inside hyaline degeneration and the cavum of liquefied uterine leiomyomas can be shown very clearly in the refraction image. And the burble structure of uterine leiomyomas, rupture of muscle fiber, conglomeration and cavum can be displayed in images which were recorded at the top of rocking curve. Therefore, the DEI is more valuable diagnoses method that we can directly observe the inside micro-structures of organs or soft tissues and the complexity of doing with a large number of pathology slices is avoid.The phase-contrast imaging (in-line holography) is used to study the structures of breast tissues, too. The absorption image of normal breast tissue has better definition than that of phase-contrast image because the normal breast tissues are compact, and the absorption of X-ray is very intensive. However, the superiority of phase-contrast imaging is obvious in the tissues of tumor. Some microstructures, which can reflect the differences of normal, benign and malignant breast tissues, are distinctly shown in phase-contrast images. The contrast of image, and the resolving power as well, are related to the distance from the sample to the detector in phase-contrast imaging. According to the contrast transfer function, the sizes of micro-calcifications are estimated to be approximately 30μm in breast cancer tissues. These results are consistent to the experimental results of DEI technique.In addition, various breast tissues are studied by synchrotron-based Fourier transform infrared spectrum (SR-FTIR). In SR-FTIR absorption spectra, there are obvious differences of spectral structures among normal, benign and malignant breast tissues. Having analyzed carefully the whole IR absorption spectrum in energy range of 900-3600 cm-1, we have a general impression: the IR absorption spectrum varies from to be featured abundantly to faint from normal breast tissue to benign tumors; while it develops from relatively smooth spectrum to much more complicated one in progression to cancer of the diseased tissue. On the other hand, the high resolving power of SR-FTIR can make closer peaks, such as the double peak at 1464 and 1474 cm-1 be visible. Some specific absorption peaks are found by SR-FTIR method, which may help us distinguish the kinds of breast tissues.At last, the kinds, relative contents and chemical state of trace elements in normal breast tissues, benign breast tumor tissues and breast cancer tissues are studied by theX-ray fluorescence (SR-XRF) and X-ray absorption fine structure (XAFS) techniques. According to the results of SR-XRF, there are same kinds of trace elements in various breast tissues, but their relative contents are different in normal breast tissue, benign breast tumor tissue and breast cancer tissue. The differences of Ca, Fe and Zn are especially obvious between the normal breast tissues and the breast tumor tissues. Comparing the contents of elements in breast tumor tissue to normal tissue, S, Cr, Mn, Ni, Cu and Se is of positive relativity, i.e. their contents in tumor tissues are increased to ones in normal tissues, but negative to K and Ca element. The contents of P in normal breast tissues are as same as in benign tissues, but a little decreasing in malignant tissues. However, Fe and Zn are of positive relativity in malignant breast tumor tissues, and negative in benign tissues.The results of the X-rays absorption near edge structure of Ca, Fe and Zn in various breast tissues show there are pre-edge structures in Fe K-edge absorption spectrum, but not in that of Ca and Zn. The change rules of Ca and Zn behind their K-edge in tumor tissues are similar, but not as same as in normal tissues. The change rule of Fe behind their K-edge in normal breast tissues is similar to that in breast cancer tissue, but not in benign tissue. The differences of radial distribution function of three elements in the tissues are definite, but the rule is not specific. These results show the circumstances of Ca, Fe and Zn are very complex in tissues, the scattering of light elements affect experimental results especially.In summary, the differences of normal tissues and tumor tissues in X-ray imaging and spectroscopy are very distinct. The results obtained by various methods are basically coincident. They can confirm and reinforce each other. DEI images can show the inside micro-structures of various breast tissues but not need a large number of pathology slices, so the DEI method could be valuable in diagnosing the cancerous tissues in their early stage. Hence, the synchrotron-based methods have definite feasibility in early diagnosis of cancer.
Keywords/Search Tags:tumor tissues, X-ray imaging, spectroscopy, synchrotron radiation
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