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In conventional phase-contrast imaging methods, an optimum distance that is essential for x-ray interference and wavefront separation must be maintained between the object and the x-ray detector. This distance determines the apparent focal size of the x-ray source and affects spatial resolution of the system. To improve the spatial resolution, we proposed a phase-contrast imaging method that eliminates the distance required for x-ray interference and wavefront separation by placing a scintillator in close contact with a Laue angle analyzer (LAA). We mathematically described the image formed by superposition of diffracted beams in two directions of LAA and introduced a method to reconstruct tomographic sections from multiple projections captured by this setup. We experimentally demonstrated the validity and the usefulness of the proposed method. Using a physical phantom, we showed that the proposed method provides higher spatial resolution than conventional x-ray dark-field imaging. The proposed method may be useful for studying and elucidating the fine 3D microanatomy and histopathology of various biological specimens.

Our previous study suggests that the cross-sectional morphology of ducts and branching of ducts in the nipple are associated with the presence of breast cancer. In this study, we evaluated whether cross-sectional morphology and duct branching of human nipple obtained by X-ray dark-field imaging tomographic technique (XDFI-CT) could predict the likelihood of the presence of intraductal cancer into the nipple. A total of 51 nipple specimens were obtained from consecutive total mastectomies performed for breast cancer in Nagoya Medical Center. After reconstructing 3D images of the nipple using XDFI-CT, the cross-sectional images and the 3D arrangement of ducts were extracted. These cross-sectional images of ducts were classified into four patterns based on the status of the lumen without being informed of pathology results. Of the four patterns, the distended ducts with heterogenous content were highly correlated with the presence of ductal carcinoma in situ confirmed by histopathology. The total number of orifices identified in the 51 specimens was 1298, and 182 (14%) at the tip and 19 (1.5%) at least 5 mm depth from the tip were composed of two or more ducts. Anatomy of nipple ducts is essential to evaluate risk of local recurrence after nipple-sparing mastectomy because cancerous spread occurs within the duct of the same segment of the mammary duct-lobular system in the in situ stage. The 3D microscale anatomy of nipple ducts revealed by XDFI-CT provides useful information to assess the risk of breast cancer involvement at the preserved portion in nipple-sparing mastectomy.

PURPOSE The integration process used as a pre-processing step in the reconstruction of differential phase-contrast X-ray CT (d-PCCT) causes the measurement noise to propagate throughout the projection image, which is leading to increased ring artifacts (RA) in the reconstructed image. It is difficult to eliminate the RA using conventional RA removal methods that were developed for the absorption-based CT field. We propose an effective method that can remove RA of d-PCCT images. METHODS The proposed method uses Laplacian images reconstructed from second-derivative projections of d-PCCT. This method is based on a conditional generative adversarial network (cGAN), whose loss function is designed by adding the L1- and L2-norm to the original cGAN. The training data were taken from a numerical phantom generated by a d-PCCT imaging simulator. To validate the applicability of the trained network, we tested its RA removal effect on test data from numerical phantoms generated randomly and actual experimental data. RESULTS The results of numerical validation using numerical phantoms showed that the proposed method improved the RA removal effect compared to conventional methods. In addition, image comparison by visual evaluation showed that only the proposed method was able to remove RA while preserving original structures in the actual biological d-PCCT images. CONCLUSION We proposed a cGAN-based method for RA removal that exploits the physical properties of d-PCCT. The proposed method was able to completely remove RA from d-PCCT images on both simulated data and biological data. We believe that this method is useful for the observation of various types of biological soft tissue.

The basic idea of X-ray dark-field imaging (XDFI), first presented in 2000, was based on the concepts used in an X-ray interferometer. In this article, we review 20 years of developments in our theoretical understanding, scientific instrumentation, and experimental demonstration of XDFI and its applications to medical imaging. We first describe the concepts underlying XDFI that are responsible for imparting phase contrast information in projection X-ray images. We then review the algorithms that can convert these projection phase images into three-dimensional tomographic slices. Various implementations of computed tomography reconstructions algorithms for XDFI data are discussed. The next four sections describe and illustrate potential applications of XDFI in pathology, musculoskeletal imaging, oncologic imaging, and neuroimaging. The sample applications that are presented illustrate potential use scenarios for XDFI in histopathology and other clinical applications. Finally, the last section presents future perspectives and potential technical developments that can make XDFI an even more powerful tool.

X-ray dark-field imaging (XDFI) utilizing a thin silicon crystal under Laue case enables visualizing three-dimensional (3D) morphological alterations of human tissue. XDFI uses refraction-contrast derived from phase shift rather than absorption as the main X-ray image contrast source to render 2D and 3D images of tissue specimens in unprecedented detail. The unique features of XDFI are its extremely high sensitivity (approximately 1000:1 compared to absorption for soft tissues under X-ray energy of around 20 keV, theoretically) and excellent resolution (8.5 μm) without requiring contrast medium or staining. Thus, XDFI-computed tomography can generate 3D virtual histological images equivalent to those of stained histological sections pathologists observe under low-power light microscopy as far as organs and tissues selected as samples in preliminary studies. This paper reviews the fundamental principles and the potential of XDFI, describes two optical setups for XDFI with examples, illustrates features of XDFI that are salient for histopathology, and presents XDFI examples of refraction-contrast images of atherosclerotic plaques, musculoskeletal tissue, neuronal tissue, and breast cancer specimens. Availability of this X-ray imaging in routine histopathological evaluations of tissue specimens would help guide clinical decision making by highlighting suspicious areas in unstained, thick sections for further sampling and analysis using conventional histopathological techniques. XDFI is a promising tool for 3D virtual histopathology.

Cribriform architecture is a histological pattern reminiscent of Swiss cheese that is commonly recognized in ductal carcinoma in situ (DCIS) of the breast observed by microscope. However, there are only a few three-dimensional studies to elucidate whether each glandular cavities of cribriform pattern are connected or not. The main reason for paucity of three-dimensional studies is that the conventional reconstruction based on histological sections requires laborious and time-consuming works. In this research, we first performed three-dimensional reconstruction of the cribriform pattern using crystal analyzer-based phase contrast technique, X-ray dark field computed tomography (XDFI-CT), which provides high contrast image of biological soft tissue with non-destructive and non-staining approach. Then, we propose a machine-learning-based method to extract the cavity from XDFI-CT images. Finally, we show that the useful information to analyze the cribriform patterns in DCIS such as the density and volume of the cavity can be obtained from the XDFI-CT images.

Purpose This paper describes and experimentally validates a methodology for improving contrast and spatial resolution of the x-ray dark-field imaging (XDFI) by cutting the monochromator-collimator asymmetrically and thinning the Laue angle analyzer. Methods We measure the spatial resolution of our XDFI setup using a test object consisting of wolfram tungsten meshes and compare it with the theoretical prediction. Using x-ray dark-field computed tomography of breast cancer specimens (lobular carcinoma in situ), we demonstrate that the resolution of XDFI is sufficient for histopathologic analysis. Results Our experimental results show that the overall spatial resolution of XDFI can be improved by approximately a factor of 2 when these modifications are implemented. The reconstructed images of breast cancer specimens provide sufficient details for radiologic histopathology. Conclusions By cutting the monochromator-collimator and thinning the Laue angle analyzer, XDFI can achieve the resolution sufficient for radiologic histopathology.

Gold nanoparticles (GNPs) have recently attracted attention in nanomedicine as novel contrast agents for cancer imaging. A decisive tomographic imaging technique has not yet been established to depict the 3-D distribution of GNPs in an object. An imaging technique known as pinhole-based X-ray fluorescence computed tomography (XFCT) is a promising method that can be used to reconstruct the distribution of GNPs from the X-ray fluorescence emitted by GNPs. We address the acceleration of data acquisition in pinhole-based XFCT for preclinical use using a multiple pinhole scheme. In this scheme, multiple projections are simultaneously acquired through a multi-pinhole collimator with a 2-D detector and full-field volumetric beam to enhance the signal-to-noise ratio of the projections; this enables fast data acquisition. To demonstrate the efficacy of this method, we performed an imaging experiment using a physical phantom with an actual multi-pinhole XFCT system that was constructed using the beamline AR-NE7A at KEK. The preliminary study showed that the multi-pinhole XFCT achieved a data acquisition time of 20 min at a theoretical detection limit of approximately 0.1 Au mg/ml and at a spatial resolution of 0.4 mm.

Purpose In this study, we demonstrate a novel imaging technique, based on ultra-small-angle X-ray scattering (USAXS) that uses a Laue-case Si wafer as the angle analyzer. Methods: We utilized the (1 1 1) diffraction plane of a 356 μm thick, symmetrically cut Si wafer as the angle analyzer, denoted by A[L]. With this device, we performed USAXS imaging experiments using 19.8 keV synchrotron X-rays. The objects we imaged were formalin-fixed, paraffin-embedded breast tumors (an invasive carcinoma and an intraductal papilloma). During image acquisition by a charge-coupled device (CCD) camera, we varied the rotation angle of the analyzer in 0.02″ steps from −2.40″ to +2.40″ around the Bragg angle. The exposure time for each image was 2 s. We determined the amount of ultra-small-angle X-ray scattering from the width of the intensity curve obtained for each local pixel during the rotation of the analyzer. Results: We acquired USAXS images of malignant and benign breast tumor specimens using the A[L] analyzer; regions with larger USAXS form brighter areas in the image. We varied the sensitivity of the USAXS image by changing the threshold level of the object rocking curve. Conclusions: The USAXS images can provide information about the internal distribution of closely packed scattering bodies in a sample with reasonable sensitivity. This information differs from that obtainable through refraction-contrast imaging. Although further validation studies will be necessary, we conclude that USAXS imaging using a Laue-case analyzer may have significant potential as a new diagnosis technique.

Purpose: High-resolution cardiac imaging and fiber analysis methods are required to understand cardiac anatomy. Although refraction-contrast x-ray CT (RCT) has high soft tissue contrast, it cannot be commonly used because it requires a synchrotron system. Microfocus x-ray CT (μCT) is another commercially available imaging modality. Approach: We evaluate the usefulness of μCT for analyzing fibers by quantitatively and objectively comparing the results with RCT. To do so, we scanned a rabbit heart by both modalities with our original protocol of prepared materials and compared their image-based analysis results, including fiber orientation estimation and fiber tracking. Results: Fiber orientations estimated by two modalities were closely resembled under the correlation coefficient of 0.63. Tracked fibers from both modalities matched well the anatomical knowledge that fiber orientations are different inside and outside of the left ventricle. However, the μCT volume caused incorrect tracking around the boundaries caused by stitching scanning. Conclusions: Our experimental results demonstrated that μCT scanning can be used for cardiac fiber analysis, although further investigation is required in the differences of fiber analysis results on RCT and μCT.

The three-dimensional (3D) structure of the human nipple has not been fully clarified. However, its importance has increased in recent years because it has become common practice to preoperatively explore the spread of breast cancer to the nipple with needle biopsy, ductoscopy, and/or ductal lavage for nipple-sparing mastectomy. Here, we demonstrated that X-ray dark-field computed tomography (XDFI-CT) is a powerful tool for reconstructing the 3D distribution pattern of human lactiferous ducts non-destructively, without contrast agent, and with high tissue contrast. Nipples amputated from mastectomy specimens of 51 patients with breast cancer were visualized three-dimensionally by XDFI-CT. First, CT images and conventionally stained tissue sections were compared to demonstrate that XDFI-CT provides 3D anatomical information. Next, the number of ducts in the nipple and the number of ducts sharing an ostium near the tip of the nipple were measured from the volume set of XDFI-CT. Finally, the 3D distribution pattern of the ducts was determined. XDFI-CT can provide images almost equivalent to those of low-magnification light microscopy of conventional hematoxylin–eosin-stained histological sections. The mean number of ducts in all cases was 28.0. The total number of ducts sharing an ostium near the tip of the nipple was 525 of 1428. The 3D distribution patterns of the ducts were classified into three types that we defined as convergent (22%), straight (39%), or divergent (39%). XDFI-CT is useful for exploring the microanatomy of the human nipple and might be used for non-invasive nipple diagnosis in the future.

Bone scintigraphy is difficult to understand the anatomical structure and quantitatively evaluate functions due to two-dimensional image, especially in the region such as sternum and pelvis, while bone SPECT providing three-dimensional image is useful for them. However, the imaging time of SPECT using many projection data is long. Shortening of the SPECT imaging time is desired. The aim of this study is to apply the image reconstruction method using total variation (TV) regularization to bone SPECT, and to examine the feasibility of bone SPECT from a small number of projections. In the image reconstruction, we used the expectation maximization-TV (EM-TV) algorithm consisting of the L1 norm regularization called TV, one of the methods of compressed sensing, and the maximum likelihood-expectation maximization (ML-EM) method, which is a statistical iterative image reconstruction method. First, it was validated by numerical phantom simulation that EM-TV algorithm could reconstruct a small number of projection data successfully. Next, bone SPECT imaging with 99mTc-MDP was performed using clinical SPECT-CT scanner, and image reconstruction was performed with equally spaced 12 out of 72 directions as projection data of a small number, and comparison with the conventional method, ML-EM, was performed. From results of bone SPECT study, the artifact which appears on the image reconstructed by ML-EM was dramatically improved by EM-TV reconstruction. In addition, EM-TV reconstruction significantly improved the quantitative accuracy in the region such as the pelvis. In conclusion, this study suggested the feasibility of bone SPECT with a small number of projections by EM-TV image reconstruction method.

We present a depth super-resolved 3D imaging method for inspection of defects in walls using terahertz swept-source optical coherence tomography. A depth profile analysis based on an annihilating filter method with noise reduction was applied for signal processing, and the results were compared with those of conventional inverse fast Fourier transform (IFFT) analysis. To evaluate the depth resolution, we measured a plastic step sample with 1 mm thickness, and its front and back surfaces were discriminated. This is corresponding to about 1/3 of the theoretical depth resolution of the conventional IFFT analysis. Moreover, we demonstrated 3D imaging of the void with a 10 mm width behind a ceramic tile and succeeded in reconstructing a significantly sharper cross-sectional void image than in the conventional analysis.

We proposed a highly sensitive transillumination imaging method with THz CW sources based on the heterodyne detection. The method was applied to tomosynthesis imaging of a 5-mm-thick wooden board to reproduce the depth information.