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O Med Sci Monit, 2005: 115 M133-38 WWW MEDSCIMONIT COM PMD:15874903 2005 02.03 X-ray diffraction-enhanced imaging of uterine 20050 leiomyomas Authors'Contribution: Chenglin Liu1. 2,34B(D, Yuan Zhang n, Xinyi Zhang. 3.BcD, Wentao Yang d A Study Design B Data Collection Weijun Peng d, Daren Shi, Peiping Zhu 5B, Yulian Tiana, Wanxia Huang 5t c Statistical Analysis D 1 Synchrotron Radiation Research Center of Fudan University, Shanghai, China 2 Physics Department of Yancheng Normal College, Yancheng Jiangsu, China E Manuscript Preparation3Physics Department, Surface Physics Laboratory(National Key laboratory)of Fudan University, Shanghai, Chir G Funds Collection Cancer Hospital, Medical Center of Fudan University, Shanghai, China s Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, Source of support: This work was supported by the National Natural Science Foundation of China (N0.10105002) Summary Background: The purpose of this study was to investigate the microstructures of a uterine leiomyoma using a synchrotron-based imaging technique Material/Methods: The tissues of different regions of a uterine leiomyoma were imaged using X-ray diffraction-en- hanced imaging Results: Compared with optical microscopy and conventional X-ray, X-ray diffraction-enhanced imaging an show not only the surface, but also the internal structure of organs or soft tissues with better contrast. Internal hyaline degeneration and the cavum of liquefied uterine leiomyomas are shown very clearly. Some microstructures, such as the myomatous burble, rupture and conglomeration of muscle fiber, and the cavum resulting from red degeneration, can be displayed in X-ray diffrac- tion-enhanced images. These microstructures can show the developmental progress of necrosis in uterine leiomyomas and indicate their potential canceration Conclusions: X-ray diffraction-enhanced imaging can clearly show intemal microstructures of uterine leiomyom making the complex procedure of doing this with a large number of pathology slices avoidable key words: uterine leiomyomas.microstructures X-ray diffraction-enhanced imaging synchrotron radiation Full-textPdf:http://www.medscimONitcom/Pub/vOl1_1/no_5/7006.pdf Word count: 2456 Figures:5 References Authors address: Xinyi Zhang, Synchrotron Radiation Research Center of Fudan University, Shanghai 200433, China -mail:xy-zhang@fudan.edu.cn Current Contents/Clinical Medicine. SCI Expanded. ISI Alerting System Index Medicus/MEDLINE.EMBASE/Excerpta Medica. Chemical Abstracts. Index Copernicus MT33

X-ray diffraction-enhanced imaging of uterine leiomyomas Chenglin Liu1,2,3ABCDEF, Yuan Zhang1BF, Xinyi Zhang1,3ABCDEFG, Wentao Yang4CD, Weijun Peng4D, Daren Shi4D, Peiping Zhu5B, Yulian Tian5B, Wanxia Huang5B 1 Synchrotron Radiation Research Center of Fudan University, Shanghai, China 2 Physics Department of Yancheng Normal College, Yancheng Jiangsu, China 3 Physics Department, Surface Physics Laboratory (National Key laboratory) of Fudan University, Shanghai, China 4 Cancer Hospital, Medical Center of Fudan University, Shanghai, China 5 Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China Source of support: This work was supported by the National Natural Science Foundation of China (No. 10105002) Summary Background: The purpose of this study was to investigate the microstructures of a uterine leiomyoma using a synchrotron-based imaging technique. Material/Methods: The tissues of different regions of a uterine leiomyoma were imaged using X-ray diffraction-en￾hanced imaging. Results: Compared with optical microscopy and conventional X-ray, X-ray diffraction-enhanced imaging can show not only the surface, but also the internal structure of organs or soft tissues with better contrast. Internal hyaline degeneration and the cavum of liquefi ed uterine leiomyomas are shown very clearly. Some microstructures, such as the myomatous burble, rupture and conglomeration of muscle fi ber, and the cavum resulting from red degeneration, can be displayed in X-ray diffrac￾tion-enhanced images. These microstructures can show the developmental progress of necrosis in uterine leiomyomas and indicate their potential canceration. Conclusions: X-ray diffraction-enhanced imaging can clearly show internal microstructures of uterine leiomyomas, making the complex procedure of doing this with a large number of pathology slices avoidable. key words: uterine leiomyomas • microstructures • X-ray diffraction-enhanced imaging • synchrotron radiation Full-text PDF: http://www.MedSciMonit.com/pub/vol_11/no_5/7006.pdf Word count: 2456 Tables: — Figures: 5 References: 16 Author’s address: Xinyi Zhang, Synchrotron Radiation Research Center of Fudan University, Shanghai 200433, China, e-mail: xy-zhang@fudan.edu.cn Authors’ Contribution: A Study Design B Data Collection C Statistical Analysis D Data Interpretation E Manuscript Preparation F Literature Search G Funds Collection Received: 2005.02.02 Accepted: 2005.02.03 Published: 2005.05.05 MT33 Diagnostics and Medical Technology © Med Sci Monit, 2005; 11(5): MT33-38 WWW.MEDSCIMONIT.COM PMID: 15874903 MT Current Contents/Clinical Medicine • SCI Expanded • ISI Alerting System • Index Medicus/MEDLINE • EMBASE/Excerpta Medica • Chemical Abstracts • Index Copernicus

Diagnostics and Medical Technology Med Sci Monit, 2005: 11(5): M133-38 BACKGROUND power of MRI and CT is usually a few millimeters [11, 121, but a resolving power of soft tissues can be attained on the Uterine leiomyomas, which result from hyperplasia of uter- order of um with the DEl technique [13]. It has several ad- he smooth muscle tissues, is a common benign tumor. About vantages in the microscopic imaging of soft tissues such as 0%o of women of reproductive age will develop such leo- uterine leiomyomas, and is of very effective clinical investi- myomas[1]. They are often found during medical examina ative value in medicine. In this paper we investigate uter- tion or laparotomy for other diseases because they are often ine leiomyomas by the DEl method and various microstruc- asymptomatic In imaging diagnoses of uterine leiomyomas, tures are revealed. Image contrast is definitely increased as B-mode ultrasound is normally the initial and convention- different contrast mechanisms are used al examining method with which myomatous liquefaction, necrosis, segregation, and the like might be preferably ob MATERIAL AND METHODS served. It is a convenient, cheap, and multi-posture clinica diagnoses, but has definite limitations due to effects from Uterine leiomyoma samples were prepared at the Cancer ntestinal peristalsis and the changing in uterine leiomy- lospital of the Medical Center of Fudan University. The mas while the patient is being examined [2]. MRI (magnetic uterine leiomyoma was removed from a patient who under- resonance imaging)is an ideal diagnostic method in deter- went myomectomy. The shape of the uterine leiomyoma was lining the relation among the myomatous character, size, ellipsoid, with lubricous surface and some tenacity. After the configuration, and position in uterine space. It can show uterine leiomyoma was cut, its cross-section was a kind of silky the substantive, space-occupying lesion in the wall of uter- muscular layer with clear color. Degeneration could not be us,but it must usually work with a contrast agent [3]. Cr distinctly seen with the naked eye. The experimental samples (computed tomography) is also provided with some char- were taken from different regions of the uterine leiomyoma. acteristics of high spatial resolution, fine definition of im- One was adjacent to the edge of the uterine leiomyoma; the ge, and inner detection of the organs. It has the highest texture was soft and slightly red(sample 1). Sample Ill was resolution for adipose, blood, and calcification composition taken from the center of the uterine leiomyoma and [4]. However, the radiation dose of CT is high; the patient its texture was hard and it had a small portion of transparent must endure long-time radiation of high-intensity X-rays. state. Sample ll was taken from the region between samples In this way it carries a definite risk of injury to patients. CT I and Ill. The specimens were cut into 2-mm-thick sections should be used cautiously especially in young female pa- measuring 12x9 mm and fixed in 10%o buffered formalin. tients to avoid injury of reproductive organs. Figure I is the schematic setup for diffraction-enhanced im- Since the middle of the 1990s, a novel imaging technology aging. The important feature of the DEl setup is the analyz- has progressed: diffractionenhanced imaging(DEl). The er crystal [14]. X-rays from the synchrotron light source pass DEl method produces the image of an object with greater through a monochromator to be translated into monoen- sharpness and clarity than the traditional radiation meth- ergetic light. The monoenergetic X-rays traverse the sam- ods as a result of the combination of one or more contrast ple, undergo diffraction by the analyzer crystal, and are fi- echanisms: absorption, refractive gradient, and small-an- nally recorded by the detector. When the X-rays traverse the gle scattering rejection [5,6]. When the character and the sample, they are refracted by very small angles(in the m structure of a tissue is pathologically altered, its refractive croradian range) due to the tiny variations in refractive index also changes and forms a gradient of refraction in- dexes of the sample. The analyzer crystal can almost elimi- dexes. This gradient can be clearly seen in DEl images; con- nate the X-rays which are scattered within a large angle by quently, the microstructure and pathological changes in the sample. The X-rays emerging from the sample and hit- soft tissue can be distinctly shown in these images. Optical ting the analyzer crystal will satisfy the conditions for Bragg icroscope can usually display the surface, but not show diffraction only for a very narrow range of incident angles he internal structures of a sample, but the DEl technique (typically on the order of a few microradians). If the X-rays is capable of observing the internal microstructures of the hat have been refracted by the sample are within the an- sample because of the high penetrability of X-rays. In re- gular acceptance range of the analyzer, they will be diffract- cent years, DEI makes the conventional characterization of ed to the detector. Otherwise, if the X-rays that have been breast cancer clearer, and has latent applications in the ear- scattered by the sample fall outside this angular acceptance ly diagnosis of disease [7, 8] ange, they will not be reflected at all. The relationship of re- flectivity on incident angle is called the rocking curve [15]. The combination of DEl and CT, called DEF-CT, might have a The rocking curve is usually a triangular-shaped curve with articular relation to the pathological histology of cancer and a full width at half maximum(FWHM) of about several m has a great many applications in medicine [9]. In addition, al- roradians. Since the resulting refraction contrast originates though the intensity of synchrotron radiation is several orders from the slope of either shoulder of the triangular-shaped of magnitude higher than medical X-rays, the synchro otron rocking curve, it depends on the FWHM as well as the tun- based DEl method has a low risk of injury to patients because ing angle. We can obtain some images at different positions its exposure time is quite short and the absorbed radiation dose of the rocking curve by tuning the analyzer crystal. These should be low enough [10]. On the other hand, DEI images pictures contain absorption, refraction, and show high contrast for soft tissues, and the microstructure of small-angle scattering is rejected) information. In the DEl the inner part of organs can be clearly viewed as well. The te- experiment, two images must be obtained when the analyzer dium of pathological diagnoses, therefore, is avoided. is tuned to the FWHM positions on either side of the ng curve. These two images contain the same absorption in At present, uterine leiomyomas larger than I cm in diam- formation but opposite refraction information. We can sepa- eter can be shown with B-mode ultrasound. The resolving rate the different information from the two images through M134

BACKGROUND Uterine leiomyomas, which result from hyperplasia of uter￾ine smooth muscle tissues, is a common benign tumor. About 20% of women of reproductive age will develop such leio￾myomas [1]. They are often found during medical examina￾tion or laparotomy for other diseases because they are often asymptomatic. In imaging diagnoses of uterine leiomyomas, B-mode ultrasound is normally the initial and convention￾al examining method with which myomatous liquefaction, necrosis, segregation, and the like might be preferably ob￾served. It is a convenient, cheap, and multi-posture clinical diagnoses, but has defi nite limitations due to effects from intestinal peristalsis and the changing in uterine leiomyo￾mas while the patient is being examined [2]. MRI (magnetic resonance imaging) is an ideal diagnostic method in deter￾mining the relation among the myomatous character, size, confi guration, and position in uterine space. It can show the substantive, space-occupying lesion in the wall of uter￾us, but it must usually work with a contrast agent [3]. CT (computed tomography) is also provided with some char￾acteristics of high spatial resolution, fi ne defi nition of im￾age, and inner detection of the organs. It has the highest resolution for adipose, blood, and calcifi cation composition [4]. However, the radiation dose of CT is high; the patient must endure long-time radiation of high-intensity X-rays. In this way it carries a defi nite risk of injury to patients. CT should be used cautiously especially in young female pa￾tients to avoid injury of reproductive organs. Since the middle of the 1990s, a novel imaging technology has progressed: diffraction-enhanced imaging (DEI). The DEI method produces the image of an object with greater sharpness and clarity than the traditional radiation meth￾ods as a result of the combination of one or more contrast mechanisms: absorption, refractive gradient, and small-an￾gle scattering rejection [5,6]. When the character and the structure of a tissue is pathologically altered, its refractive index also changes and forms a gradient of refraction in￾dexes. This gradient can be clearly seen in DEI images; con￾sequently, the microstructure and pathological changes in soft tissue can be distinctly shown in these images. Optical microscopes can usually display the surface, but not show the internal structures of a sample, but the DEI technique is capable of observing the internal microstructures of the sample because of the high penetrability of X-rays. In re￾cent years, DEI makes the conventional characterization of breast cancer clearer, and has latent applications in the ear￾ly diagnosis of disease [7,8]. The combination of DEI and CT, called DEI-CT, might have a particular relation to the pathological histology of cancer and has a great many applications in medicine [9]. In addition, al￾though the intensity of synchrotron radiation is several orders of magnitude higher than medical X-rays, the synchrotron￾based DEI method has a low risk of injury to patients because its exposure time is quite short and the absorbed radiation dose should be low enough [10]. On the other hand, DEI images show high contrast for soft tissues, and the microstructure of the inner part of organs can be clearly viewed as well. The te￾dium of pathological diagnoses, therefore, is avoided. At present, uterine leiomyomas larger than 1 cm in diam￾eter can be shown with B-mode ultrasound. The resolving power of MRI and CT is usually a few millimeters [11,12], but a resolving power of soft tissues can be attained on the order of µm with the DEI technique [13]. It has several ad￾vantages in the microscopic imaging of soft tissues such as uterine leiomyomas, and is of very effective clinical investi￾gative value in medicine. In this paper we investigate uter￾ine leiomyomas by the DEI method and various microstruc￾tures are revealed. Image contrast is defi nitely increased as different contrast mechanisms are used. MATERIAL AND METHODS Uterine leiomyoma samples were prepared at the Cancer Hospital of the Medical Center of Fudan University. The uterine leiomyoma was removed from a patient who under￾went myomectomy. The shape of the uterine leiomyoma was ellipsoid, with lubricous surface and some tenacity. After the uterine leiomyoma was cut, its cross-section was a kind of silky muscular layer with clear color. Degeneration could not be distinctly seen with the naked eye. The experimental samples were taken from different regions of the uterine leiomyoma. One was adjacent to the edge of the uterine leiomyoma; the texture was soft and slightly red (sample I). Sample III was taken from the center region of the uterine leiomyoma and its texture was hard and it had a small portion of transparent state. Sample II was taken from the region between samples I and III. The specimens were cut into 2-mm-thick sections measuring 12×9 mm2 and fi xed in 10% buffered formalin. Figure 1 is the schematic setup for diffraction-enhanced im￾aging. The important feature of the DEI setup is the analyz￾er crystal [14]. X-rays from the synchrotron light source pass through a monochromator to be translated into monoen￾ergetic light. The monoenergetic X-rays traverse the sam￾ple, undergo diffraction by the analyzer crystal, and are fi - nally recorded by the detector. When the X-rays traverse the sample, they are refracted by very small angles (in the mi￾croradian range) due to the tiny variations in refractive in￾dexes of the sample. The analyzer crystal can almost elimi￾nate the X-rays which are scattered within a large angle by the sample. The X-rays emerging from the sample and hit￾ting 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 an￾gular acceptance range of the analyzer, they will be diffract￾ed to the detector. Otherwise, if the X-rays that have been scattered by the sample fall outside this angular acceptance range, they will not be refl ected at all. The relationship of re- fl ectivity on incident angle is called the rocking curve [15]. The rocking curve is usually a triangular-shaped curve with a full width at half maximum (FWHM) of about several mi￾croradians. Since the resulting refraction contrast originates from the slope of either shoulder of the triangular-shaped rocking curve, it depends on the FWHM as well as the tun￾ing angle. We can obtain some images at different positions of the rocking curve by tuning the analyzer crystal. These pictures contain absorption, refraction, and extinction (i.e. small-angle scattering is rejected) information. In the DEI experiment, two images must be obtained when the analyzer is tuned to the FWHM positions on either side of the rock￾ing curve. These two images contain the same absorption in￾formation but opposite refraction information. We can sepa￾rate the different information from the two images through Diagnostics and Medical Technology Med Sci Monit, 2005; 11(5): MT33-38 MT34

Med Sci Monit,2005:115}:M33-38 Liu Cet al-DE images of uterine leiomyomas lonization chamber Sample 2 Detector lonization chamber Storage ning Analyzer crystal Figure 1 Schematic experimental setup of the diffraction-enhanced imaging 多断 Figure 2. DEl images of sample l Images taken at the peak of the rocking curve(A), apparent absorption image( B)and refraction image(o) b-burble structure; hd-hyaline degeneration; r-rupture; (-cavum a pixel-by-pixel algorithm [16]. when two images are add- recorded as the analyzer was tuned at the peak position of d, we can obtain the apparent absorption image that has the rocking curve. It contains the information about the ab- only the absorption, with no refraction effect, but with weak sorption and the extinction(small-angle scattering is reject- extinction. When the two images are subtracted we can ob ed), but not the refraction information. It can be considered tain the refraction image in which the edge effect has been as a"pure"absorption imaging of sample I. Two other im enhanced. The refraction image is extraordinarily sensitive ages were also recorded by the CCD when the analyzer was o changes in the refractive index of the sample tuned to the FWHM positions on either side of the rock- ing curve. As mentioned above, these images contain the RESULTS same absorption, but opposite refraction information. The image in Figure 2(B)is called the apparent absorption im- The DEl experiments were carried out at the topography age of sample I, which is produced by the addition of these station from a 4WIA beamline of the Beijing Synchrotron two images. Figure 2(C) is the refraction image of sample I Radiation Facility(BSRF). The X-ray source of the topogra- and is obtained after the two above images are subtracted. phy station uses wiggler radiation with a wide energy range (3-22 ke V) which is approximately coherent at 48 m from Figure 3(A)is the optical microscope picture of sample I, in the source. The radiation is made monochromatic by Si which only some surface configurations of uterine leiomy (1 11)single crystals in the experiment. The energy of the ma tissue are shown. Only when the inside hyaline degen- monochromatic X-ray is 8 kev when the incident angle of eration and the cavum of the tissues have made the surface the radiation is 14.3. The analyzer is also a Si(1 11)crys- dingy can the internal pathological changes be observed in tal that can be fixed at an axis in order that it can be tuned the optical microscope. Figures 3(B),(C), and(D)are the at different positions of the rocking curve. The D nplificatory images of the different regions of the es are recorded with a Microphotonics CCD or Fuji IX80 DEl image recorded by industry X-ray films at the peak po- industry X-ray films, their resolving power being 10.9 Hm sition of the rocking curve and 2.3 Hm, respectively. In the imaging process, the sam- ple is positioned on the stage, the maximum light spot on Figures 4(A)and 5(A)are the X-ray DEl images of samples the sample is approximately 15x12 mm, and the distance II and Ill, respectively, recorded by the CCD at the peak of between the specimen and detector is about I m. The over- the rocking curve Figures 4(B)and 5(B) are the partially all exposure is controlled as a constant. magnified images of Figure 4(A)and Figure 5(A), respec tively. A few microstructures, but not many, can be seen In the DEl experiment, we tuned the analyzer at the var- for sample ll, as shown in Figure 4(A), but some irregul iant positions of the rocking curve and recorded the DEI structures forming the agglomerate of the muscle fiber are nages by the CCD. Figure 2(A)is the image of sample I shown for sample Ill(Figure 5(A)) MI35

a pixel-by-pixelalgorithm [16]. When two images are add￾ed, we can obtain the apparent absorption image that has only the absorption, with no refraction effect, but with weak extinction. When the two images are subtracted, we can ob￾tain the refraction image in which the edge effect has been enhanced. The refraction image is extraordinarily sensitive to changes in the refractive index of the sample. RESULTS The DEI experiments were carried out at the topography station from a 4W1A beamline of the Beijing Synchrotron Radiation Facility (BSRF). The X-ray source of the topogra￾phy station uses wiggler radiation with a wide energy range (3-22 keV) which is approximately coherent at 43 m from the source. The radiation is made monochromatic by Si (1 1 1) single crystals in the experiment. The energy of the monochromatic X-ray is 8 keV when the incident angle of the radiation is 14.3°. The analyzer is also a Si (1 1 1) crys￾tal that can be fi xed at an axis in order that it can be tuned at different positions of the rocking curve. The DEI imag￾es are recorded with a Microphotonics CCD or Fuji IX80 industry X-ray fi lms, their resolving power being 10.9 µm and 2.3 µm, respectively. In the imaging process, the sam￾ple is positioned on the stage, the maximum light spot on the sample is approximately 15×12 mm2 , and the distance between the specimen and detector is about 1 m. The over￾all exposure is controlled as a constant. In the DEI experiment, we tuned the analyzer at the var￾iant positions of the rocking curve and recorded the DEI images by the CCD. Figure 2(A) is the image of sample I recorded as the analyzer was tuned at the peak position of the rocking curve. It contains the information about the ab￾sorption and the extinction (small-angle scattering is reject￾ed), but not the refraction information. It can be considered as a “pure” absorption imaging of sample I. Two other im￾ages were also recorded by the CCD when the analyzer was tuned to the FWHM positions on either side of the rock￾ing curve. As mentioned above, these images contain the same absorption, but opposite refraction information. The image in Figure 2(B) is called the apparent absorption im￾age of sample I, which is produced by the addition of these two images. Figure 2(C) is the refraction image of sample I and is obtained after the two above images are subtracted. Figure 3(A) is the optical microscope picture of sample I, in which only some surface confi gurations of uterine leiomyo￾ma tissue are shown. Only when the inside hyaline degen￾eration and the cavum of the tissues have made the surface dingy can the internal pathological changes be observed in the optical microscope. Figures 3(B), (C), and (D) are the partial amplifi catory images of the different regions of the DEI image recorded by industry X-ray fi lms at the peak po￾sition of the rocking curve. Figures 4(A) and 5(A) are the X-ray DEI images of samples II and III, respectively, recorded by the CCD at the peak of the rocking curve. Figures 4(B) and 5(B) are the partially magnifi ed images of Figure 4(A) and Figure 5(A), respec￾tively. A few microstructures, but not many, can be seen for sample II, as shown in Figure 4(A), but some irregular structures forming the agglomerate of the muscle fi ber are shown for sample III (Figure 5(A)). Figure 1. Schematic experimental setup of the diff raction-enhanced imaging. Figure 2. DEI images of sample I. Images taken at the peak of the rocking curve (A); apparent absorption image (B) and refraction image (C). b – burble structure; hd – hyaline degeneration; r – rupture; c – cavum. A B C Med Sci Monit, 2005; 11(5): MT33-38 Liu C et al – DEI images of uterine leiomyomas MT35 MT

Diagnostics and Medical Technology Med Sci Monit, 2005: 11(5): M133-38 Figure 3. The microstructure picture of sample l. Picture a shows the surface of sample l with an optical microscope Pictures B, C, and D are DEl images recorded in the regions B, C, and D of sample l, denoted by the rectangles in picture(A). They show the burble structure of uterine leiomyomas(B), rupture of musde fiber(q), and conglomeration(black arrows) and cavum (white arrow )(D) Figure 4. X-ray DEl image of sample ll, the microstructure picture(A)and the partially magnified image( B)of the small rectangle area in picture A DISCUSSION Figure 2(A) contains only the absorption information of the sample, but Figure 2(B) contains the absorption in Apparent absorption image and refraction image formation as well as the small-angle scattering, which de- creases the image contrast. The image recorded from the The apparent absorption image of sample I(Figure 2(B)) top position of the rocking curve is therefore more useful is similar to the conventional X-ray image and it is difficult than the conventional medical image. Furthermore, the to distinguish the structure of soft tissue. Because the tis- refraction image is even more valuable in that we can di- sue of the uterine leiomyoma shows hyaline degeneration ectly observe the inside structure of the sample with higl X-ray absorption is weakened and there is large brilliant contrast and do not need large numbers of pathology slic s, pot in the Figure 2(B). Figure 2(B)includes less micro- es. The concrete detail of the microstructure can be seen ructure information than Figure 2(A). The reason is that very well in Figure 2(C), in which the hyaline degenera- M136

DISCUSSION Apparent absorption image and refraction image The apparent absorption image of sample I (Figure 2(B)) is similar to the conventional X-ray image and it is diffi cult to distinguish the structure of soft tissue. Because the tis￾sue of the uterine leiomyoma shows hyaline degeneration, X-ray absorption is weakened and there is large brilliant spot in the Figure 2(B). Figure 2(B) includes less micro￾structure information than Figure 2(A). The reason is that Figure 2(A) contains only the absorption information of the sample, but Figure 2(B) contains the absorption in￾formation as well as the small-angle scattering, which de￾creases the image contrast. The image recorded from the top position of the rocking curve is therefore more useful than the conventional medical image. Furthermore, the refraction image is even more valuable in that we can di￾rectly observe the inside structure of the sample with high contrast and do not need large numbers of pathology slic￾es. The concrete detail of the microstructure can be seen very well in Figure 2(C), in which the hyaline degenera￾Figure 3. The microstructure picture of sample I. Picture A shows the surface of sample I with an optical microscope. Pictures B, C, and D are DEI images recorded in the regions B, C, and D of sample I, denoted by the rectangles in picture (A). They show the burble structure of uterine leiomyomas (B), rupture of muscle fi ber (C), and conglomeration (black arrows) and cavum (white arrow) (D). A B C D Figure 4. X-ray DEI image of sample II, the microstructure picture (A) and the partially magnifi ed image (B) of the small rectangle area in picture A. A B Diagnostics and Medical Technology Med Sci Monit, 2005; 11(5): MT33-38 MT36

Med Sci Monit,2005:115}:M33-38 Liu Cet al-DE images of uterine leiomyomas Figure 5. X-ray DEl image of sample l, the microstructure picture(A)and the partially magnified image(B)of the small rectangular area in picture A tion and the cavum of liquefied uterine leiomyomas are ation of the center region of the uterine leiomyoma is more ery clearly seen. serious than in other regions. There is an extraordinarily large cavum with irregular shape as shown in Figure 5(B),a partially magnified image of Figure 5(A). The large cavum forms the inside angiorrhexis of the uterine leiomyoma. The burble structure of uterine leiomyomas can be distinct- These can show the developmental progress of the necrosis ter. At the same time, a small cavum(denoted by an arrow bodings of uterine leiomyoma canceration as wey al fore. ly seen in Figure 8(B). Their fiber is about 20 um in diame- of uterine leiomyoma. They are one of the potenti in Figure 3(B))obviously appears due to the liquid degen- eration In Figure 3(C), the bundle-shaped myomatous fib- CONCLUSIONS an be distinctly seen in the left part of this picture; thei size is about 50 um in diameter and they are packed togeth- DEI images can clearly show the internal microstructures er closely. There is also the fiber rupture which results from of uterine leiomyomas, including the burble structure, hy- the uniformity or asymmetric liquefaction of the uterine lei- aline degeneration and rupture of muscle fibers, red de- omyoma as shown in Figure 3(C)by the arrow. In the cent- generation, and cavum of myomatous inside uterine leia- er of the uterine leiomyoma there is large-scale degenera- as. The internal hyaline degeneration and the cavum tion Blurry and disordered muscle fiber is shown in Figure of liquefied uterine leiomyomas can be shown very clear 3(D). There are a few uterine leiomyoma fibers which are ly in the refraction image. The burble structure of uterine about several hundreds um length and about 30 um in di- leiomyomas, the rupture of muscle fiber, conglomeration ameter. Some fibers have been assembled and form the con- and cavum can be displayed in images which were record- glomeration, whose size is unclear (the black arrow posi- ed at the top of the rocking curve. Therefore, DEI is a very tions in Figure 3(D). At the same time there is a big cavum valuable diagnostic method in that we can directly observ (the white arrow position in Figure 3(D)). Furthermore, the internal microstructures of organs or soft tissues, and the microstructure of a myomatous fiber with a diameter the complexity of performing a large number of patholo- of about 30 um can be distinctly shown inside the cavum. All these irregular structures are special symptoms of uter- myoma and can be very useful in finding malignant REFERENCES: pathological changes in uterine leiomyomas. sson M et al: Expression of Bcl-2, Bcl-x, For sample lI there are some small bright spots which are McL-l Bax and Bak in human leiomyomas and myometrium calcification of the uterine leiomyoma because of the cal- Biochemistry Molecular Biology, 2002: 80: 77-83 cium salt deposition in it over a long time( Figure 4(A) There are also several smooth muscle fibers which are blur- and the bundle of fibers cannot be gdd4919:15145 4(A). The partially magnified image Figure 4(B)enables us 3. Xu J. Yu Z, Jiang W: CT diagnosis value of hysteromyoma(add 71 to see some irregular microstructures of uterine leiomyo- ma tissue. These structures have pole or petal shape with a 4. Liu L, Zhou S: Image diagnosis of broad ligament leiomyoma length of approximately a few hundred micrometers. They J China Radiology, 2000: 34: 118-21(in Chinese) are red degeneration resulted from congestion, thrombo 5. Suortti P, Thomlinson W: Medical application of synchrotron radiation. Phys Med BioL, 2003; 48: Rl-R35 sis, hemolysis, and red-cell exosmosis. The spread of the 6. Zhong Z, Thomlinson w, Chapman D et al: Implementation of petal-shape structure is the most distinct characteristic of enhanced imaging experiments: at the NSLS and AsP Nue Instrum Meth Phys Res, 2000: 450: 556-b8 There are some small calcified substances to be seen in sam trast techniques: diffraction enhanced imaging and propagation. Proc of SPlE.2003:5030:26673 ple Ill, as shown in Figure 5(A). This shows that the degener- MI37

tion and the cavum of liquefi ed uterine leiomyomas are very clearly seen. Microstructures The burble structure of uterine leiomyomas can be distinct￾ly seen in Figure 3(B). Their fi ber is about 20 µm in diame￾ter. At the same time, a small cavum (denoted by an arrow in Figure 3(B)) obviously appears due to the liquid degen￾eration. InFigure 3(C), the bundle-shaped myomatous fi b￾er can be distinctly seen in the left part of this picture; their size is about 50 µm in diameter and they are packed togeth￾er closely. There is also the fi ber rupture which results from the uniformity or asymmetric liquefaction of the uterine lei￾omyoma as shown in Figure 3(C) by the arrow. In the cent￾er of the uterine leiomyoma there is large-scale degenera￾tion. Blurry and disordered muscle fi ber is shown in Figure 3(D). There are a few uterine leiomyoma fi bers which are about several hundreds µm length and about 30 µm in di￾ameter. Some fi bers have been assembled and form the con￾glomeration, whose size is unclear (the black arrow posi￾tions in Figure 3(D)). At the same time there is a big cavum (the white arrow position in Figure 3(D)). Furthermore, the microstructure of a myomatous fi ber with a diameter of about 30 µm can be distinctly shown inside the cavum. All these irregular structures are special symptoms of uter￾ine leiomyoma and can be very useful in fi nding malignant pathological changes in uterine leiomyomas. For sample II there are some small bright spots which are calcifi cation of the uterine leiomyoma because of the cal￾cium salt deposition in it over a long time (Figure 4(A)). There are also several smooth muscle fi bers which are blur￾ry and the bundle of fi bers cannot be seen clearly inFigure 4(A). The partially magnifi ed image Figure 4(B) enables us to see some irregular microstructures of uterine leiomyo￾ma tissue. These structures have pole or petal shape with a length of approximately a few hundred micrometers. They are red degeneration resulted from congestion, thrombo￾sis, hemolysis, and red-cell exosmosis. The spread of the petal-shape structure is the most distinct characteristic of red degeneration. There are some small calcifi ed substances to be seen in sam￾ple III, as shown in Figure 5(A). This shows that the degener￾ation of the center region of the uterine leiomyoma is more serious than in other regions. There is an extraordinarily large cavum with irregular shape as shown in Figure 5(B), a partially magnifi ed image of Figure 5(A). The large cavum forms the inside angiorrhexis of the uterine leiomyoma. These can show the developmental progress of the necrosis of uterine leiomyoma. They are one of the potential fore￾bodings of uterine leiomyoma canceration as well. CONCLUSIONS DEI images can clearly show the internal microstructures of uterine leiomyomas, including the burble structure, hy￾aline degeneration and rupture of muscle fi bers, red de￾generation, and cavum of myomatous inside uterine leio￾myomas. The internal hyaline degeneration and the cavum of liquefi ed uterine leiomyomas can be shown very clear￾ly in the refraction image. The burble structure of uterine leiomyomas, the rupture of muscle fi ber, conglomeration and cavum can be displayed in images which were record￾ed at the top of the rocking curve. Therefore, DEI is a very valuable diagnostic method in that we can directly observe the internal microstructures of organs or soft tissues, and the complexity of performing a large number of patholo￾gy slices is avoided. REFERENCES: 1. Wu X, Blanck A, Olovsson M et al: Expression of Bcl-2, Bcl-x, Mcl-1, Bax and Bak in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause. Journal of Steroid Biochemistry & Molecular Biology, 2002; 80: 77–83 2. Ueda H, Togashi K, Konishi I et al: Unusual appearances of uter￾ine leiomyomas: MR imaging fi ndings and their histopathologic back￾grounds. Radiographics, 1999; 19: S131–S145 3. Xu J, Yu Z, Jiang W: CT diagnosis value of hysteromyoma (add 71 example analysis ). Radiology Practice, 2000; 15: 187–189 (in Chinese) 4. Liu L, Zhou S: Image diagnosis of broad ligament leiomyoma. J China Radiology, 2000; 34: 118–21 (in Chinese) 5. Suortti P, Thomlinson W: Medical application of synchrotron radiation. Phys Med Biol, 2003; 48: R1–R35 6. Zhong Z, Thomlinson W, Chapman D et al: Implementation of diffraction enhanced imaging experiments: at the NSLS and ASP. Nucl Instrum Meth Phys Res, 2000; 450: 556–68 7. Fiedler S, Pagot E, Cloetens P et al: Evaluation of two phase con￾trast techniques: diffraction enhanced imaging and propagation. Proc of SPIE, 2003; 5030: 266–73 Figure 5. X-ray DEI image of sample III, the microstructure picture (A) and the partially magnifi ed image (B) of the small rectangular area in picture A. A B Med Sci Monit, 2005; 11(5): MT33-38 Liu C et al – DEI images of uterine leiomyomas MT37 MT

Diagnostics and Medical Technology Med Sci Monit, 2005: 11(5): M133-38 8. Hasnah MO, Zhong Z, Oltulu O et al: Diffraction enhanced im- 12. Dai Z: The pathology of hysteromyoma. Chinese Joumal of Medicine, east cancer specimens. Med Phys, 2002; 2002:37(4):13-14( in Chinese) 13. Lewis RA, Rogers KD, Hall C et al: Diffraction enhanced imaging: im- 9. Fiedler S, Bravin A, Keyrilainen J et al: Imaging lobular breast proved contrast, lower dose X-ray. Proc of SPIE, 2002; 4682: 286-97 arcinoma:comparison of synchrotron radiation DEN-CT technique with clinical CT, mammography and histology. Phys. Med. Biol. 2004; 14. Kiss MZ, Sayers DE, Zhong Z: Measurement of imaging contrast using diffraction enhanced imaging. Phys Med Biol, 2005: 48: 325- 0. Arfelli F, Assante M, Bonvicini V et al: Low-dose phase contrast X-ray medical imaging, Phys Med Biol, 1998: 43: 2845-52 crystal reflections at Elettra and NSLS. Proc of SPIE, 2002 4682:255-66 11. Yamashita Y, Torashima M, Takahashi M et al: Hyperintense oma at T, weighted MR imaging: differentiation with dynamic enhanced 16. Chapman D, Thomlinson w, Johnston RE et al: Diffraction enhanced X-ray imaging, Phys Med Biol, 1997; 42: 2015-25 993:189:721 MT38

8. Hasnah MO, Zhong Z, Oltulu O et al: Diffraction enhanced im￾aging contrast mechanisms in breast cancer specimens. Med Phys, 2002; 29: 2216–21 9. Fiedler S, Bravin A, Keyrilainen J et al: Imaging lobular breast carcinoma: comparison of synchrotron radiation DEI-CT technique with clinical CT, mammography and histology. Phys. Med. Biol, 2004; 49: 175–88 10. Arfelli F, Assante M, Bonvicini V et al: Low-dose phase contrast X-ray medical imaging, Phys Med Biol, 1998; 43: 2845–52 11. Yamashita Y, Torashima M, Takahashi M et al: Hyperintense uterine leiomy￾oma at T2 weighted MR imaging: differentiation with dynamic enhanced MR imaging and clinical implications. Radiology, 1993; 189: 721 12. Dai Z: The pathology of hysteromyoma. Chinese Journal of Medicine, 2002; 37(4): 13–14 (in Chinese) 13. Lewis RA, Rogers KD, Hall CJ et al: Diffraction enhanced imaging: im￾proved contrast, lower dose X-ray. Proc of SPIE, 2002; 4682: 286–97 14. Kiss MZ, Sayers DE, Zhong Z: Measurement of imaging contrast using diffraction enhanced imaging. Phys Med Biol, 2003; 48: 325–40 15. Rigon L, Zhong Z, Arfelli F et al: Diffraction enhanced imaging utiliz￾ing different crystal refl ections at Elettra and NSLS. Proc of SPIE, 2002; 4682: 255–66 16. Chapman D, Thomlinson W, Johnston RE et al: Diffraction enhanced X-ray imaging, Phys Med Biol, 1997; 42: 2015–25 Diagnostics and Medical Technology Med Sci Monit, 2005; 11(5): MT33-38 MT38

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