## 6 Application to Biomedical Research  
Several imaging modalities, such as X-ray CT, magnetic resonance imaging (MRI), ultrasonography, optical imaging, and positron emission tomography, are widely used in biomedical studies. Imaging modalities with high spatial resolution on a micrometer scale are needed for biological research using small animals, a critical need in the field of pathology in particular. Conventional absorption-based micro-X-ray CT yields high contrast for strongly mineralized tissues such as bones and teeth [35], but it usually provides insufficient contrast for soft tissues composed of light elements. High-spatial-resolution phase-contrast X-ray CT imaging has the potential to overcome this problem [24; 36; 37; 38]. Among the many PCXI methods developed for biomedical imaging, CXI has the greatest sensitivity for the observation of biological soft tissues. Phase-contrast X-ray CT using CXI enables visualization of the fine morphological structures of biological soft tissues such as cancerous lesions in humans [36], rabbits [24], mice [39], and rats [40; 41; 42] and noncancerous organs (e.g., hepatic vessels) of rats [43]. It also enables visualization of the micro-structures of the vessels and glomeruli in the kidneys [44], heart, and spleen [45]. In addition, CXI enables assessment of the pathological hallmarks of [PERSON]'s disease, namely, amyloid  
Figure 6: Sectional (**a**,**b**) and three-dimensional (**c**) volume rendering images of mouse brain. Reprinted with permission from Ref. [32]. Copyright 2013, IOP Publishing. plaques, which are not visible with conventional absorption-based X-ray imaging because of their very small size and low density differences [46]. While MRI is widely used for accurate diagnosis and characterization of soft tissue tumors, CXI is more suitable for visualizing soft tissue tumors. A previous study of CXI compared with MRI using ex-vivo imaging of a formalin-fixed colon cancer implanted tumor demonstrated that CXI affords higher image quality than 4.74-T MRI (Table 4) [39]. Thus, for imaging at high spatial resolution, CXI is the most suitable method. CXI shows minute density differences caused by various morphological structures within soft tissue tumors, such as solid cancerous masses, cystic and fibrous necrotic lesions, hemorrhages, and tumor vessels [39; 40; 41; 42]. The resultant CT images resemble pathological pictures (magnification \(\times\)20) and clearly show the pathological features of tumors [42] (Figure 7). Minutely differing densities within tumors visualized using CXI correspond especially well to the different types of neoplastic cells in soft tissue tumors observed in pathological images [42]. Moreover, CXI provides three-dimensional (3D) information, yielding volume data with a density resolution of 0.3 mg/cm\({}^{3}\). Furthermore, it is not labor-intensive and time-consuming such as histopathological staining. These 3D information capabilities enable the imaging of entire organs, which in turn enables the localization and size determination of various pathological lesions [42] (Figure 8). 3D images of tumor micro-vessels reconstructed from PX-CXI images without the use of contrast media enable evaluation of the vascular architecture (Figure 9) [40]. This ability to visualize pathological details and tumor vessels on the basis of density differences is an important breakthrough in the field of preclinical anticancer research. \begin{table}
\begin{tabular}{l l l} \hline \hline  & **CXI** & **4.74-T MRI** \\ \hline Volumetric resolution & (0.018)\({}^{3}\) mm\({}^{3}\) & (0.075)\({}^{3}\) mm\({}^{3}\) \\ Acquisition time & 2 h & 1.8 h \\ SNR * in nonnecrotic cancer lesions & 48.4 & 12.1 \\ \hline \hline \end{tabular}  
* SNR: Signal-to-noise ratio.  
\end{table} 
Table 4: Comparative study with CXI and MRI using colon cancer specimen [39]. Figure 7: Tumor-bearing rat testis: (**A**) sectional CT image obtained by CXI; (**B**) corresponding histopathological (HE-stained) gray-scale image and (**C**) color image.