AJP - Heart Information on EB 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 294: H1094-H1100, 2008. First published December 14, 2007; doi:10.1152/ajpheart.01149.2007
0363-6135/08 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
294/2/H1094    most recent
01149.2007v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shinohara, M.
Right arrow Articles by Momose, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shinohara, M.
Right arrow Articles by Momose, A.

INNOVATIVE METHODOLOGY

Atherosclerotic plaque imaging using phase-contrast X-ray computed tomography

Masakazu Shinohara,1 Tomoya Yamashita,1 Hideto Tawa,1 Masafumi Takeda,1 Naoto Sasaki,1 Tomofumi Takaya,1 Ryuji Toh,1 Akihisa Takeuchi,2 Takuji Ohigashi,2 Kunio Shinohara,2 Seinosuke Kawashima,1 Mitsuhiro Yokoyama,1 Ken-ichi Hirata,1 and Atsushi Momose3

1Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe; 2Japan Synchrotron Radiation Research Institute, Hyogo; and 3Department of Advanced Materials Science, Graduate School of Frontier Science, The University of Tokyo, Tokyo, Japan

Submitted 4 October 2007 ; accepted in final form 10 December 2007


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Reliable, noninvasive imaging modalities to characterize plaque components are clinically desirable for detecting unstable coronary plaques, which cause acute coronary syndrome. Although recent clinical developments in computed tomography (CT) have enabled the visualization of luminal narrowing and calcified plaques in coronary arteries, the identification of noncalcified plaque components remains difficult. Phase-contrast X-ray CT imaging has great potentials to reveal the structures inside biological soft tissues, because its sensitivity to light elements is almost 1,000 times greater than that of absorption-contrast X-ray imaging. Moreover, a specific mass density of tissue can be estimated using phase-contrast X-ray CT. Ex vivo phase-contrast X-ray CT was performed using a synchrotron radiation source (SPring-8, Japan) to investigate atherosclerotic plaque components of apolipoprotein E-deficient mice. Samples were also histologically analyzed. Phase-contrast X-ray CT at a spatial resolution of 10–20 µm revealed atherosclerotic plaque components easily, and thin fibrous caps were detected. The specific mass densities of these plaque components were quantitatively estimated. The mass density of lipid area was significantly lower (1.011 ± 0.001766 g/ml) than that of smooth muscle area or collagen area (1.057 ± 0.001407 and 1.080 ± 0.001794 g/ml, respectively). Moreover, the three-dimensional assessment of plaques could provide their anatomical information. Phase-contrast X-ray CT can estimate the tissue mass density of atherosclerotic plaques and detect lipid-rich areas. It can be a promising noninvasive technique for the investigation of plaque components and detection of unstable coronary plaques.

synchrotron radiation; atherosclerotic plaque component; tissue-mass density of plaque component

ATHEROSCLEROSIS IS A SYSTEMIC disease in which the clinical manifestations weakly correlate with its extent and with the severity of luminal stenosis. Coronary plaque disruption and subsequent thrombosis in coronary atherosclerosis lead to a potentially life-threatening disease, acute coronary syndrome (11, 15). Clinical evidence suggests that atherosclerotic plaque components are important predictors of plaque stability and clinical events. The risk of plaque rupture appears to depend on the plaque components rather than the severity of stenosis. Most ruptures occur in "unstable" plaques containing a soft lipid-rich core, covered by a thin and inflamed cap of fibrous tissue (39).

Invasive techniques, such as coronary angiography, intravascular ultrasound, and optical coherent tomography, can reveal the luminal diameter or stenosis, wall thickness, and plaque volume and components (16). However, to detect an unstable plaque that leads to acute coronary syndrome, reliable, noninvasive imaging modalities for the characterization of plaque components are clinically desirable. Currently, two emerging and promising techniques, namely, computed tomography (CT) and magnetic resonance imaging (MRI), are widely accepted by the medical community because they are noninvasive and have the potential to evaluate luminal stenosis and characterize plaque components (8).

In the past, CT techniques have enabled the visualization of luminal narrowing and calcified plaques in coronary arteries. Because of the small dimensions of the coronary arteries, as well as their rapid motion, imaging is very challenging. Technical developments over the past several years, especially the introduction of multislice CT scanners, have made coronary CT angiography quite reliable for some patient subgroups (1, 3). However, the discrimination of noncalcified plaque components remains difficult. Noncalcified atherosclerotic plaques mainly consist of deposited lipids, inflammatory cells, smooth muscle cells, and collagen (9, 10, 34, 39). The present clinical X-ray CT is based on absorption-contrast X-ray imaging, in which images are generated by the differences in X-ray absorption, as determined by the linear attenuation coefficient. The differences in X-ray absorption by biological soft tissues are very small, and, therefore, the present X-ray CT is not highly sensitive in differentiating plaque components.

MRI can differentiate plaque components with reasonable accuracy based on biophysical and biochemical parameters, such as chemical composition, water content, physical state, molecular motion, and diffusion (8). Thus far, the characterization of plaques in the carotid arteries and aorta by using MRI has proven to be very sensitive and specific (41, 42); however, due to its limitations in temporal and spatial resolutions, MRI cannot effectively characterize coronary arterial plaques.

X-rays have the nature of waves, and the shift of the wave when it passes through an object is called the X-ray phase shift. Phase-contrast X-ray imaging has great potential to reveal the structures inside soft tissues, because the sensitivity of this method to light elements is almost 1,000 times greater than that of the absorption-contrast X-ray method (18, 36). Several X-ray imaging techniques are being developed for the detection of X-ray phase shift (2, 7, 17, 40). Among these methods, the interferometric method using a crystal X-ray interferometer is the most sensitive for detecting the differences in the refractive indexes of soft tissues. For the first time, we applied this method to differentiate atherosclerotic plaque components.

The purpose of this study was to image atherosclerotic lesions by using phase-contrast X-ray CT, and to investigate whether this method could identify differences in plaque components that would lead to the detection of "unstable" atherosclerotic plaques.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Phase-contrast X-ray imaging system. The phase-contrast X-ray imaging system was previously described in detail (19, 38). It consists of a monolithic X-ray interferometer, a phase shifter, an object cell, and an X-ray detector. A sample cell filled with water was inserted into the beam path. Interference patterns were detected using a charge-coupled device detector with a 10-µm luminescent screen and lens coupling. The charge-coupled device chip had 3.14 x 3.14 µm pixels. Experiments were conducted at SPring-8 (BL20XU, JASRI, Harima, Japan) with the approval of the Japan Synchrotron Radiation Research Institute (JASRI) as the Medical-Biology Trial Use (Proposal No. 2006A1811). The X-ray energy was set at 12.4 KeV.

Phase-contrast X-ray projection image and CT. The phase shift {Phi} is given as {Phi} = (2{pi}/{lambda}){int}{delta}dr, where {delta} is the refractive index decrement of the sample, r is a position along the X-ray beam, and {lambda} is an X-ray wavelength. The phase map that describes the spatial distribution of the phase shift within a sample cannot be obtained directly by using the interferometer. Phase-shifting interferometry is used to generate a phase map (17, 20).

The phase map of the sample was obtained from several interference patterns, which were measured sequentially by changing the phase of the reference beam. The phase-contrast X-ray CT images mapped the variation of the d{delta} between the tissue and water at 12.4 KeV, where d{delta} is the difference between the refractive index of the tissue and that of water at 12.4 KeV X-ray energy. Because the X-ray beam was fixed, the samples had to be rotated inside the cell; the number of projections was 400 at 180°. The d{delta} values of specimens were evaluated in seven to eight regions of the phase-contrast X-ray CT images. The d{delta} is proportional to the mass density ({rho}) (21, 22), which is estimated from d{delta} with the following formula: {rho} = (d{delta} + {delta}w)/{delta}w, where the refractive index of water (w) is 1 – {delta}w ({delta}w = 74.0 x 10–8). The CT images were three-dimensionally rendered using the AVS Express software (Advanced Visual Systems).

Animal preparation. Apolipoprotein E (ApoE)-deficient [knockout (KO)] mice (ApoE-KO mice) on a C57BL/6 genetic background were weaned at 4 wk of age and fed a normal diet or a high cholesterol diet (1.25% cholesterol, 7.5% cocoa butter, 7.5% casein, 0.5% sodium cholate; Oriental Yeast Japan) (28). The animals were provided the diet and water ad libitum and maintained on a 12:12-h light-dark cycle. All animal experiments were conducted according to the guidelines for animal experiments of Kobe University Graduate School of Medicine.

Male ApoE-KO mice fed a normal diet were euthanized at the age of 36 wk, and those fed the high cholesterol diet, at the age of 12 wk. After mice were anesthetized with pentobarbital sodium (80 mg/kg intraperitoneally), the aortas were perfused with physiological saline and perfusion-fixed with neutralized buffered formalin. For the phase-contrast CT experiments, the aortic roots and right common carotid arteries were dissected.

Histological analysis of atherosclerotic plaque. After the phase-contrast CT experiments, the arterial samples were embedded in optimum cutting temperature compounds (Tissue-Tek; Sakura Finetechnical, Tokyo, Japan) and sectioned (10 µm thick). The sections corresponding to the phase-contrast CT images were histologically and immunohistochemically analyzed.

An anti-mouse monocyte/macrophage antibody (MOMA-II) and an anti-human smooth muscle actin antibody (1A4) were commercially obtained (BMA Biomedicals and DAKO, respectively). Macrophage- and smooth muscle-containing lesions were immunohistochemically analyzed. For the immunohistochemical staining, biotinylated anti-rat and anti-mouse antibodies (DAKO) were used as secondary antibodies. Incubation with streptavidin peroxidase was followed by the addition of the substrate 3'3'-diaminobenzidine. Lipid-containing lesions were stained with Sudan-III. Collagen contents were stained with Masson's trichrome.

Statistical analysis. The d{delta} data were expressed as means ± SE. The significance of the difference between group means was analyzed by one-way ANOVA, followed by post hoc tests (PRISM 4.0, GraphPad). Values of P < .05 were considered statistically significant.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
Imaging of atherosclerotic plaque differences between normal diet-fed and high-cholesterol died-fed ApoE-KO mice. Atherosclerotic lesions of the aortic sinus were investigated using phase-contrast X-ray CT and histological analysis. Figure 1 shows a representative atherosclerotic plaque in a normal diet-fed ApoE-KO mouse, and Fig. 2, in a high-cholesterol diet-fed ApoE-KO mouse. These atherosclerotic plaques were imaged using phase-contrast X-ray CT under the same gray scale. The phase-contrast X-ray CT image in Fig. 1 shows a relatively homogeneous high-d{delta} lesion; however, that in Fig. 2 shows a lesion with areas of high and low d{delta}.


Figure 1
View larger version (95K):
[in this window]
[in a new window]

  		Fig. 1. Representative atherosclerotic lesion in the aortic sinus of the apolipoprotein E (ApoE)-knockout (KO) mouse (36 wk of age) fed a normal diet. This lesion was investigated using phase-contrast computed tomography (CT); hematoxylin and eosin (HE) staining, Sudan-III, and collagen (Masson's trichrome) staining; and anti-macrophage (MOMA-II) and anti-smooth muscle (1A4) immunohistochemistry. Scale bars = 100 µm; original magnification, x100. The white arrow indicates a low difference between the refractive index of the tissue and that of water at 12.4 KeV X-ray energy (d{delta}) and mass density area in the CT image. The corresponding Masson's trichrome staining shows low collagen content in the same area (black arrow).

 

Figure 2
View larger version (82K):
[in this window]
[in a new window]

  		Fig. 2. Representative atherosclerotic lesion in the aortic sinus of the ApoE-KO mouse (12 wk of age) fed a high-cholesterol diet for 8 wk. This lesion was investigated using phase-contrast CT; HE staining, Sudan-III, and collagen (Masson's trichrome) staining; and anti-macrophage (MOMA-II) and anti-smooth muscle (1A4) immunohistochemistry. Scale bars = 100 µm; original magnification, x100. The arrowheads indicate a thin fibrous cap (15- to 20-µm thick), consisting of smooth muscles (positively stained by 1A4) and collagen (positively stained by Masson's trichrome).

 
The corresponding histological analysis revealed many differences in the plaque components between the ApoE-KO mice fed the two different diets. In the normal diet-fed ApoE-KO mouse (Fig. 1), the lipid plaque component was small and limited to its luminal surface. Immunohistochemical analysis showed only weak MOMA-II staining, indicating only slight macrophage infiltration. Almost the entire plaque area was positively stained by Masson's trichrome, showing that collagen was the main component of this plaque. Immunohistochemical analysis using 1A4 demonstrated infiltration of smooth muscle cells into the plaque.

On the other hand, in the high-cholesterol diet-fed ApoE-KO mouse (Fig. 2), Sudan-III staining showed that atherosclerotic plaque formed a large lipid pool. Invasion by many macrophages was strongly indicated by MOMA-II immunohistochemistry. Collagen and smooth muscle components were fewer than those in the normal diet-fed mouse (Fig. 1).

Phase-contrast CT images characterized plaque components as well as the histological analyses did. Regarding the atherosclerotic plaque in the normal diet-fed ApoE-KO mouse (Fig. 1), the low-d{delta} area in the CT image (arrow) corresponded to the area of lower collagen content, as revealed by Masson's trichrome staining. With regard to the plaque in the high-cholesterol diet-fed ApoE-KO mouse (Fig. 2), the lower d{delta} area in the CT image also corresponded to the less or no collagen-containing area, and it was filled with a large amount of lipid. Phase-contrast CT imaging can reveal the differences in atherosclerotic plaque components, particularly the lipid component. The arrowheads in Fig. 2 indicate a thin fibrous cap (15- to 20-µm thick), comprising smooth muscles (positively stained by 1A4 immunohistochemistry) and collagen (positively stained by Masson's trichrome). This thin fibrous cap was detectable in the corresponding CT image.

Quantitative analysis of the mass density of atherosclerotic plaque components. Areas containing smooth muscle cells, lipid, and collagen were defined using the corresponding histological analyses. The refractive index d{delta} of these three components was measured. The measured d{delta} values and their association with mass densities are shown in Fig. 3. The lipid area showed the low d{delta} (0.79 ± 0.13 x 10–8) and mass density (1.011 ± 0.001766 g/ml). The d{delta} and mass density of the smooth muscle area were 4.18 ± 0.10 x 10–8 and 1.057 ± 0.001407 g/ml, and those of the collagen area were 5.93 ± 0.13 x 10–8 and 1.080 ± 0.001794 g/ml, respectively. These three d{delta} values and mass densities were found to be significantly different by Tukey's multiple-comparison test. Phase-contrast X-ray CT can directly estimate tissue-mass density and can reveal very small differences in mass density among the atherosclerotic plaque components.


Figure 3
View larger version (10K):
[in this window]
[in a new window]

  		Fig. 3. The mean d{delta} values and specific mass densities of the various components of atherosclerotic plaques. The d{delta} is proportional to the specific mass density ({rho}) (21, 22), which is estimated using the following formula: {rho} = (d{delta} + {delta}w)/{delta}w, where the refractive index of water (w) is 1 – {delta}w({delta}w = 74.0 x 10–8). The lipid area shows a low d{delta} (0.79 ± 0.13 x 10–8) and mass density (1.011 ± 0.001766 g/ml). The smooth muscle and collagen areas show high d{delta} (4.18 ± 0.10 and 5.93 ± 0.13 x 10–8, respectively) and mass density (1.057 ± 0.001407 and 1.08 ± 0.001794 g/ml, respectively). *P < .05; {dagger}P < .01.

 
Imaging of atherosclerotic plaques: visualization of the thin fibrous cap. Figure 4 illustrates a representative atherosclerotic lesion of the right common carotid artery in a high-cholesterol diet-fed ApoE-KO mouse that was investigated using phase-contrast X-ray CT and histological analysis. This lesion showed a large lipid pool and thin fibrous cap. The arrowheads indicate a thin fibrous cap of 15- to 20-µm thickness, and the arrows indicate one of 10- to 15-µm thickness. The spatial resolution of the corresponding phase-contrast X-ray CT image is adequately high to detect these thin fibrous caps.


Figure 4
View larger version (55K):
[in this window]
[in a new window]

  		Fig. 4. Representative atherosclerotic lesion in the right common carotid artery of the ApoE-KO mouse (12 wk of age) that was fed a high-cholesterol diet for 8 wk. This lesion was investigated using phase-contrast CT; and HE staining, Sudan-III, and collagen (Masson's trichrome) staining. Scale bars = 100 µm; original magnification, x100. The arrowheads indicate a thin fibrous cap of 15- to 20-µm thickness, and the arrows indicate a thin fibrous cap of 10- to 15-µm thickness.

 
Three-dimensional visualization of atherosclerotic plaques. A three-dimensional rendering of the right common carotid artery from the high-cholesterol diet-fed ApoE-KO mouse is shown in Fig. 5. The continuity of the atherosclerotic plaque was easily detectable. Phase-contrast X-ray CT imaging can depict the atherosclerotic lesions from any direction and simultaneously provide anatomical information regarding both luminal stenosis and plaque components.


Figure 5
View larger version (70K):
[in this window]
[in a new window]

  		Fig. 5. Three-dimensional rendering of the right common carotid artery of the ApoE-KO mouse that was fed a high-cholesterol diet. Scale bar = 1 mm.

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
For the first time, we performed the phase-contrast X-ray CT imaging of atherosclerotic plaques by using synchrotron radiation. Quantitative differences in d{delta} and mass density among plaque components were clearly revealed using phase-contrast X-ray CT, owing to its high sensitivity.

We prepared and examined two different atherosclerotic plaques by feeding mice either a normal or a high-cholesterol diet. It has been reported that different compositions of atherogenic diet, especially the cholesterol level and the presence of cholic acid, induced different plaque morphology in ApoE-KO mice (12, 25, 43). In the ApoE-KO mouse that was fed a normal diet for 36 wk, collagen- and smooth muscle-rich plaques were formed (Fig. 1); these plaques had characteristics similar to the stable plaques in humans. On the other hand, the ApoE-KO mouse that was fed a high-cholesterol diet for 8 wk from 4 wk of age developed lipid-rich plaques with thin fibrous caps (Fig. 2). These plaques showed characteristics similar to the unstable plaques in humans. Phase-contrast X-ray CT can detect the differences between these two kinds of plaques by means of the d{delta} values and mass densities of the plaque components.

With regard to light elements, the d{delta} value is proportional to the mass density (21); therefore, the mass densities of the atherosclerotic plaque components were easily estimated using phase-contrast X-ray CT. Phase-contrast X-ray imaging directly yields a very important parameter of biological soft tissues: mass density (Fig. 3). Unstable plaques contain large lipid-rich cores, and this lipid exhibits lower mass density than collagen and smooth muscles. Therefore, it is reasonable that the assessment of specific tissue-mass density at high spatial resolution can detect the lipid-rich core in atherosclerotic plaques. It may be possible to detect the lipid core in the atherosclerotic plaques by setting a threshold level for the d{delta} or mass density. As illustrated in Fig. 3, a d{delta} level of 1 ~ 2 x 10–8 can be used to detect the lipid core of atherosclerotic plaques in mice. The d{delta} or mass density values of human atherosclerotic plaque components may differ from those of mice. Therefore, a phase-contrast X-ray CT investigation of human atherosclerotic plaques is required.

In this experiment, a crystal X-ray interferometer was used to detect the X-ray phase shift. Phase-contrast X-ray CT using the X-ray interferometer has demonstrated rabbit and human cancer lesions (21, 35, 37) and facilitated the quantitative analysis of amyloid plaques in a mouse model of Alzheimer's disease (27). Physiological saline can be used as the contrast agent for angiography. Liver vessels filled with physiological saline were clearly imaged using phase-contrast X-ray imaging (38). Phase-contrast X-ray imaging has the potential to detect small differences in the mass densities between normal tissues and cancer lesions or between normal tissues and physiological saline.

This system requires highly brilliant X-rays, such as synchrotron radiation; therefore, it has not been easily used for clinical purposes thus far. Recently, however, a Talbot-type imaging interferometer raised the possibility of yielding quantitative differential phase-contrast images with conventional X-ray tubes (23, 29). It is highly probable that phase-contrast X-ray imaging can be applied to clinical trials in the near future. Another limitation of the present study is that the imaging targets are limited to only ex vivo samples because of the narrow field of view (5 x 5 mm). With the use of a monolithic X-ray interferometer made from a silicon ingot, the maximum achievable image size is limited by its diameter. The Talbot-type imaging interferometer is currently being developed to obtain a larger field of view and could resolve this problem.

Recent developments in clinical CT have provided a great amount of information about atherosclerotic diseases. Luminal stenosis and plaque calcifications in the coronary arteries can be detected by absorption-contrast clinical CT imaging with high sensitivity and specificity. However, fundamentally, absorption-contrast X-ray imaging is not highly sensitive to detect noncalcified soft plaque components. Previous observations have shown that the CT attenuation within "fibrous" plaques (mean attenuation values of 91–116 Hounsfield units) is greater than within "lipid-rich" plaques (mean attenuation values of 47–71 Hounsfield units) (5, 6, 13, 14, 24, 26, 32). However, because of the large variability of the measured density values within the plaques (5, 30) and the substantial influence of contrast density within the coronary lumen on these values (4, 31), the classification of coronary atherosclerotic plaques using CT is difficult. In an ex vivo experiment on human atherosclerotic plaques, the present X-ray CT technique could not display an adequate difference in the mean attenuation values to identify noncalcified plaque components (33). To overcome this limitation of absorption-contrast X-ray imaging, the application of phase-contrast X-ray imaging in the cardiovascular field is very promising.

The phase-contrast X-ray CT technique can achieve higher sensitivity compared with absorption-contrast X-ray CT imaging for the evaluation of biological soft tissues and provide a new quantitative parameter: the "tissue-mass density." Moreover, it appears to be a promising technique for the investigation of plaque components and the detection of unstable plaques.


   GRANTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This study was supported in part by health science research grants from the Ministry of Health, Labor, and Welfare, Tokyo, Japan.


   ACKNOWLEDGMENTS
 
We greatly appreciate Dr. Yoshihiko Takeda's kind technical support (data analyses and reconstruction of CT images).


   FOOTNOTES
 

Address for reprint requests and other correspondence: T. Yamashita, Division of Cardiovascular Medicine, Dept. of Internal Medicine, Kobe Univ. Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan (e-mail: tomoya{at}med.kobe-u.ac.jp)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. Achenbach S. Computed tomography coronary angiography. J Am Coll Cardiol 48: 1919–1928, 2006.[Abstract/Free Full Text]
  2. Bonse U, Hart M. An X-ray interferometer. Appl Phys Lett 6: 155–156, 1965.[CrossRef]
  3. Budoff MJ, Achenbach S, Blumenthal RS, Carr JJ, Goldin JG, Greenland P, Guerci AD, Lima JA, Rader DJ, Rubin GD, Shaw LJ, Wiegers SE. Assessment of coronary artery disease by cardiac computed tomography: a scientific statement from the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology. Circulation 114: 1761–1791, 2006.[Free Full Text]
  4. Cademartiri F, Mollet NR, Runza G, Bruining N, Hamers R, Somers P, Knaapen M, Verheye S, Midiri M, Krestin GP, de Feyter PJ. Influence of intracoronary attenuation on coronary plaque measurements using multislice computed tomography: observations in an ex vivo model of coronary computed tomography angiography. Eur Radiol 15: 1426–1431, 2005.[CrossRef][Web of Science][Medline]
  5. Carrascosa PM, Capunay CM, Garcia-Merletti P, Carrascosa J, Garcia MF. Characterization of coronary atherosclerotic plaques by multidetector computed tomography. Am J Cardiol 97: 598–602, 2006.[CrossRef][Web of Science][Medline]
  6. Caussin C, Ohanessian A, Ghostine S, Jacq L, Lancelin B, Dambrin G, Sigal-Cinqualbre A, Angel CY, Paul JF. Characterization of vulnerable nonstenotic plaque with 16-slice computed tomography compared with intravascular ultrasound. Am J Cardiol 94: 99–104, 2004.[CrossRef][Web of Science][Medline]
  7. Davis T, Gao D, Gureyev T. Phase-contrast imaging of weakly absorbing materials using hard X-rays. Nature 373: 595–598, 1995.[CrossRef]
  8. Fayad ZA, Fuster V, Nikolaou K, Becker C. Computed tomography and magnetic resonance imaging for noninvasive coronary angiography and plaque imaging: current and potential future concepts. Circulation 106: 2026–2034, 2002.[Free Full Text]
  9. Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes (1). N Engl J Med 326: 242–250, 1992.[Web of Science][Medline]
  10. Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes (2). N Engl J Med 326: 310–318, 1992.[Web of Science][Medline]
  11. Fuster V, Moreno PR, Fayad ZA, Corti R, Badimon JJ. Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol 46: 937–954, 2005.[Abstract/Free Full Text]
  12. Getz GS, Reardon CA. Diet and murine atherosclerosis. Arterioscler Thromb Vasc Biol 26: 242–249, 2006.[Abstract/Free Full Text]
  13. Leber AW, Becker A, Knez A, von Ziegler F, Sirol M, Nikolaou K, Ohnesorge B, Fayad ZA, Becker CR, Reiser M, Steinbeck G, Boekstegers P. Accuracy of 64-slice computed tomography to classify and quantify plaque volumes in the proximal coronary system: a comparative study using intravascular ultrasound. J Am Coll Cardiol 47: 672–677, 2006.[Abstract/Free Full Text]
  14. Leber AW, Knez A, Becker A, Becker C, von Ziegler F, Nikolaou K, Rist C, Reiser M, White C, Steinbeck G, Boekstegers P. Accuracy of multidetector spiral computed tomography in identifying and differentiating the composition of coronary atherosclerotic plaques: a comparative study with intracoronary ultrasound. J Am Coll Cardiol 43: 1241–1247, 2004.[Abstract/Free Full Text]
  15. Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 104: 365–372, 2001.[Free Full Text]
  16. MacNeill BD, Lowe HC, Takano M, Fuster V, Jang IK. Intravascular modalities for detection of vulnerable plaque: current status. Arterioscler Thromb Vasc Biol 23: 1333–1342, 2003.[Abstract/Free Full Text]
  17. Momose A. Demonstration of phase-contrast X-ray computed tomography using an x-ray interferometer. Nucl Instrum Methods A352: 622–628, 1995.[CrossRef]
  18. Momose A, Fukuda J. Phase-contrast radiographs of nonstained rat cerebellar specimen. Med Phys 22: 375–379, 1995.[CrossRef][Web of Science][Medline]
  19. Momose A, Koyama I, Hamaishi Y, Yoshikawa H, Takeda T, Wu J, Itai Y, Takai K, Uesugi K, Suzuki Y. Phase-contrast microtomography using an X-ray interferometer having a 40-µm analyzer. J Phys IV France 104: 599–602, 2003.
  20. Momose A, Takeda T, Itai Y. Blood vessels: depiction at phase-contrast X-ray imaging without contrast agents in the mouse and rat-feasibility study. Radiology 217: 593–596, 2000.[Abstract/Free Full Text]
  21. Momose A, Takeda T, Itai Y, Hirano K. Phase-contrast X-ray computed tomography for observing biological soft tissues. Nat Med 2: 473–475, 1996.[CrossRef][Web of Science][Medline]
  22. Momose A, Takeda T, Itai Y, Hirano K. Tomographic image reconstruction using x-ray phase information. Proc Soc Photo Opt Instrum Eng 2708: 674–684, 1996.
  23. Momose A, Yashiro W, Takeda Y, Suzuki Y, Hattori T. Phase tomography by X-ray Talbot interferometry for biological imaging. Jpn J Appl Phys 45: 52–54, 2006.
  24. Moselewski F, Ropers D, Pohle K, Hoffmann U, Ferencik M, Chan RC, Cury RC, Abbara S, Jang IK, Brady TJ, Daniel WG, Achenbach S. Comparison of measurement of cross-sectional coronary atherosclerotic plaque and vessel areas by 16-slice multidetector computed tomography versus intravascular ultrasound. Am J Cardiol 94: 1294–1297, 2004.[CrossRef][Web of Science][Medline]
  25. Nakashima Y, Plump AS, Raines EW, Breslow JL, Ross R. ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb 14: 133–140, 1994.[Abstract/Free Full Text]
  26. Nikolaou K, Sagmeister S, Knez A, Klotz E, Wintersperger BJ, Becker CR, Reiser MF. Multidetector-row computed tomography of the coronary arteries: predictive value and quantitative assessment of non-calcified vessel-wall changes. Eur Radiol 13: 2505–2512, 2003.[CrossRef][Web of Science][Medline]
  27. Noda-Saita K, Yoneyama A, Shitaka Y, Hirai Y, Terai K, Wu J, Takeda T, Hyodo K, Osakabe N, Yamaguchi T, Okada M. Quantitative analysis of amyloid plaques in a mouse model of Alzheimer's disease by phase-contrast X-ray computed tomography. Neuroscience 138: 1205–1213, 2006.[CrossRef][Web of Science][Medline]
  28. Paigen B, Morrow A, Holmes PA, Mitchell D, Williams RA. Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis 68: 231–240, 1987.[CrossRef][Web of Science][Medline]
  29. Pfeiffer F, Weitkamp T, Bunk O, David C. Phase retrieval and differential phase-contrast imaging with low-brilliance X-ray sources. Nature Physics 2: 258–261, 2006.[CrossRef][Web of Science]
  30. Pohle K, Achenbach S, Macneill B, Ropers D, Ferencik M, Moselewski F, Hoffmann U, Brady TJ, Jang IK, Daniel WG. Characterization of non-calcified coronary atherosclerotic plaque by multi-detector row CT: comparison to IVUS. Atherosclerosis 190: 174–180, 2007.[CrossRef][Web of Science][Medline]
  31. Schroeder S, Flohr T, Kopp AF, Meisner C, Kuettner A, Herdeg C, Baumbach A, Ohnesorge B. Accuracy of density measurements within plaques located in artificial coronary arteries by X-ray multislice CT: results of a phantom study. J Comput Assist Tomogr 25: 900–906, 2001.[CrossRef][Web of Science][Medline]
  32. Schroeder S, Kopp AF, Baumbach A, Meisner C, Kuettner A, Georg C, Ohnesorge B, Herdeg C, Claussen CD, Karsch KR. Noninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography. J Am Coll Cardiol 37: 1430–1435, 2001.[Abstract/Free Full Text]
  33. Schroeder S, Kuettner A, Wojak T, Janzen J, Heuschmid M, Athanasiou T, Beck T, Burgstahler C, Herdeg C, Claussen CD, Kopp AF. Non-invasive evaluation of atherosclerosis with contrast enhanced 16 slice spiral computed tomography: results of ex vivo investigations. Heart 90: 1471–1475, 2004.[Abstract/Free Full Text]
  34. Stary HC. Natural history and histological classification of atherosclerotic lesions: an update. Arterioscler Thromb Vasc Biol 20: 1177–1178, 2000.[Free Full Text]
  35. Takeda T, Momose A, Hirano K, Haraoka S, Watanabe T, Itai Y. Human carcinoma: early experience with phase-contrast X-ray CT with synchrotron radiation–comparative specimen study with optical microscopy. Radiology 214: 298–301, 2000.[Abstract/Free Full Text]
  36. Takeda T, Momose A, Itai Y, Wu J, Hirano K. Phase-contrast imaging with synchrotron X-rays for detecting cancer lesions. Acad Radiol 2: 799–803, 1995.[CrossRef][Web of Science][Medline]
  37. Takeda T, Momose A, Ueno E, Itai Y. Phase-contrast X-ray CT image of breast tumor. J Synchrotron Radiat 5: 1133–1135, 1998.[CrossRef][Web of Science][Medline]
  38. Takeda T, Momose A, Wu J, Yu Q, Zeniya T, Thet Thet L, Yoneyama A, Itai Y. Vessel imaging by interferometric phase-contrast X-ray technique. Circulation 105: 1708–1712, 2002.[Abstract/Free Full Text]
  39. Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 20: 1262–1275, 2000.[Free Full Text]
  40. Wilkins S, Gureyev T, Gao D. Phase-contrast imaging using polychromatic hard x-rays. Nature 384: 335–338, 1996.[CrossRef]
  41. Worthley SG, Helft G, Fuster V, Fayad ZA, Rodriguez OJ, Zaman AG, Fallon JT, Badimon JJ. Noninvasive in vivo magnetic resonance imaging of experimental coronary artery lesions in a porcine model. Circulation 101: 2956–2961, 2000.[Abstract/Free Full Text]
  42. Yuan C, Zhang SX, Polissar NL, Echelard D, Ortiz G, Davis JW, Ellington E, Ferguson MS, Hatsukami TS. Identification of fibrous cap rupture with magnetic resonance imaging is highly associated with recent transient ischemic attack or stroke. Circulation 105: 181–185, 2002.[Abstract/Free Full Text]
  43. Zhang SH, Reddick RL, Burkey B, Maeda N. Diet-induced atherosclerosis in mice heterozygous and homozygous for apolipoprotein E gene disruption. J Clin Invest 94: 937–945, 1994.[Web of Science][Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
294/2/H1094    most recent
01149.2007v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shinohara, M.
Right arrow Articles by Momose, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shinohara, M.
Right arrow Articles by Momose, A.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2008 by the American Physiological Society.