Three-dimensional microanatomy of human nipple visualized by X-ray dark-field computed tomography.

PURPOSE: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: XDFI-CT is useful for exploring the microanatomy of the human nipple and might be used for non-invasive nipple diagnosis in the future.

Improvement of the depth resolution of swept-source THz-OCT for non-destructive inspection.

We construct a terahertz swept source optical coherence tomography system using a continuous-wave diode multiplier source in the 600-GHz band for defect inspection in multilayer objects and evaluate its performance. Using this system, we image a multilayer plastic sample to demonstrate the effectiveness of nondestructive three-dimensional imaging. To enhance the depth resolution, we apply an annihilating filter to the analysis and confirm that two surfaces of a 1-mm-thick plastic plate can be resolved. In addition, the repeatability of measured thicknesses is 0.22 mm. These values are approximately one-half and one-tenth of the resolution achievable by conventional Fourier analysis, respectively.

Limited view reconstruction for differential phase-contrast computed tomography.

This paper describes an algebraic reconstruction algorithm that uses total variation (TV) regularization for differential phase contrast computed tomography (DPC-CT) using a limited number of views. In order to overcome over-flattening inherent in TV regularization, a two-step reconstruction process is used: we first reconstruct tomographic images of gradient refractive index from differential projections with TV regularization; these images are then used to compute tomographic images of refractive index by solving the Poisson equation. We incorporate TV regularization in the reconstruction process because the distribution of gradient refractive index is much more flattened than the refractive index. Simulations of the proposed method demonstrate that it can achieve satisfactory image quality from a much smaller number of projections than is required by the Nyquist sampling theorem. We experimentally prove the feasibility of the proposed method using dark field imaging optics at PF-14C beamline at the Photon Factory, KEK. The differential phase contrast projection data was experimentally acquired from a biological sample and DPC-CT images were reconstructed. We show that far fewer projections are needed when the proposed algorithm is used.

Crystal analyser-based X-ray phase contrast imaging in the dark field: implementation and evaluation using excised tissue specimens.

OBJECTIVES: We demonstrate the soft tissue discrimination capability of X-ray dark-field imaging (XDFI) using a variety of human tissue specimens. METHODS: The experimental setup for XDFI comprises an X-ray source, an asymmetrically cut Bragg-type monochromator-collimator (MC), a Laue-case angle analyser (LAA) and a CCD camera. The specimen is placed between the MC and the LAA. For the light source, we used the beamline BL14C on a 2.5-GeV storage ring in the KEK Photon Factory, Tsukuba, Japan. RESULTS: In the eye specimen, phase contrast images from XDFI were able to discriminate soft-tissue structures, such as the iris, separated by aqueous humour on both sides, which have nearly equal absorption. Superiority of XDFI in imaging soft tissue was further demonstrated with a diseased iliac artery containing atherosclerotic plaque and breast samples with benign and malignant tumours. XDFI on breast tumours discriminated between the normal and diseased terminal duct lobular unit and between invasive and in-situ cancer. CONCLUSIONS: X-ray phase, as detected by XDFI, has superior contrast over absorption for soft tissue processes such as atherosclerotic plaque and breast cancer. KEY POINTS: • X-ray dark field imaging (XDFI) can dramatically increase sensitivity of phase detection. • XDFI can provide enhanced soft tissue discrimination. • With XDFI, abnormal anatomy can be visualised with high spatial/contrast resolution.

A deep-learning-based scatter correction with water equivalent path length map for digital radiography.

We proposed a new deep learning (DL) model for accurate scatter correction in digital radiography. The proposed network featured a pixel-wise water equivalent path length (WEPL) map of subjects with diverse sizes and 3D inner structures. The proposed U-Net model comprises two concatenated modules: one for generating a WEPL map and the other for predicting scatter using the WEPL map as auxiliary information. First, 3D CT images were used as numerical phantoms for training and validation, generating observed and scattered images by Monte Carlo simulation, and WEPL maps using Siddon's algorithm. Then, we optimised the model without overfitting. Next, we validated the proposed model's performance by comparing it with other DL models. The proposed model obtained scatter-corrected images with a peak signal-to-noise ratio of 44.24 ± 2.89 dB and a structural similarity index measure of 0.9987 ± 0.0004, which were higher than other DL models. Finally, scatter fractions (SFs) were compared with other DL models using an actual phantom to confirm practicality. Among DL models, the proposed model showed the smallest deviation from measured SF values. Furthermore, using an actual radiograph containing an acrylic object, the contrast-to-noise ratio (CNR) of the proposed model and the anti-scatter grid were compared. The CNR of the images corrected using the proposed model are 16% and 82% higher than those of the raw and grid-applied images, respectively. The advantage of the proposed method is that no actual radiography system is required for collecting training dataset, as the dataset is created from CT images using Monte Carlo simulation.

Phase-contrast visualization of human tissues using superimposed wavefront imaging of diffraction-enhanced x-rays.

BACKGROUND: Phase-contrast computed tomography (CT) using high-brilliance, synchrotron-generated x-rays enable three-dimensional (3D) visualization of microanatomical structures within biological specimens, offering exceptionally high-contrast images of soft tissues. Traditional methods for phase-contrast CT; however, necessitate a gap between the subject and the x-ray camera, compromising spatial resolution due to penumbral blurring. Our newly developed technique, Superimposed Wavefront Imaging of Diffraction-enhanced x-rays (SWIDeX), leverages a Laue-case Si angle analyzer affixed to a scintillator to convert x-rays to visible light, capturing second-order differential phase contrast images and effectively eliminating the distance to the x-ray camera. This innovation achieves superior spatial resolution over conventional methods. PURPOSE: In this paper, the imaging principle and CT reconstruction algorithm based on SWIDeX are presented in detail and compared with conventional analyzer-based imaging (ABI). It also shows the physical setup of SWIDeX that provides the resolution preserving second-order differential images for reconstruction. We compare the spatial resolution and the sensitivity of SWIDeX to conventional ABI. METHODS: To demonstrate high-spatial resolution achievable by SWIDeX, the internal structures of four human tissues-ductal carcinoma in situ, normal stomach, normal pancreas, and intraductal papillary mucinous neoplasm of the pancreas-were visualized using an imaging system configured at the Photon Factory's BL14B beamline under the High Energy Accelerator Research Organization (KEK). Each tissue was thinly sliced after imaging, stained with hematoxylin and eosin (H&E) for conventional microscope-based pathology. RESULTS: A comparison of SWIDeX-CT and pathological images visually demonstrates the effectiveness of SWIDeX-CT for biological tissue imaging. SWIDeX could generate clearer 3D images than existing analyzer-based phase-contrast methods and accurately delineate tissue structures, as validated against histopathological images. CONCLUSIONS: SWIDeX can visualize important 3D structures in biological soft tissue with high spatial resolution and can be an important tool for providing information between the disparate scales of clinical and pathological imaging.

THz phase-contrast computed tomography based on Mach-Zehnder interferometer using continuous wave source: proof of the concept.

In this study, we propose a THz computed tomography (CT) method based on phase contrast, which retrieves the phase shift information at each data point through a phase modulation technique using a Mach-Zehnder interferometer with a continuous wave (CW) source. The THz CT is based on first-generation CT, which acquires a set of projections by translational and rotational scans using a thin beam. From the phase-shift projections, we reconstruct a spatial distribution of refractive indices in a cross section of interest. We constructed a preliminary system using a highly coherent CW THz source with a frequency of 0.54 THz to prove the concept and performed an imaging experiment using phantoms to investigate its imaging features such as artifact-immune imaging, quantitative measurement, and selective detection.

Embedded soft-tissue image mechanism of a small animal shell with synchrotron-based micro-CT.

Synchrotron-based micro-CT was utilized to image the embedded biological soft-tissue of a small animal shell. Micro-CT images of the biological soft-tissue were acquired using 20, 25, and 27 keV synchrotron X-rays with contrast agents, such as water, physiological saline and iodine. Visualized the complex features of the animal at the above energies with water, physiological saline and iodine. The choice of the optimum energy was chosen based on the contrast mechanisms to know more about soft-matter and the associated internal complex biological features of the small animal shell. This way, the images at 27 keV (optimum energy) was reasonably acceptable for better visualization of the interior micro-architecture, such as soft-anatomy, physiology and internal organs of the animal with better visibility. The introduction of water, physiological, or iodine as contrast agents is shown to enhance minute image features in synchrotron-based tomographic imaging.

Crystal optics simulations for delineation of the three-dimensional cellular nuclear distribution using analyzer-based refraction-contrast computed tomography.

Refraction-contrast computed tomography (RCT) using a refractive angle analyzer of Si perfect crystal can reconstruct the three-dimensional structure of biological soft tissue with contrast comparable to that of stained two-dimensional pathological images. However, the blurring of X-ray beam by the analyzer has prevented improvement of the spatial resolution of RCT, and the currently possible observation of tissue structure at a scale of approximately 20 µm provides only limited medical information. As in pathology, to differentiate between benign and malignant forms of cancer, it is necessary to observe the distribution of the cell nucleus, which is approximately 5-10 µm in diameter. In this study, based on the X-ray dynamical diffraction theory using the Takagi-Taupin equation, which calculates the propagation of X-ray energy in crystals, an analyzer crystal optical system depicting the distribution of cell nuclei was investigated by RCT imaging simulation experiments in terms of the thickness of the Laue-case analyzer, the camera pixel size and the difference in spatial resolution between the Bragg-case and Laue-case analyzers.

Convolution reconstruction algorithm for refraction-contrast computed tomography using a Laue-case analyzer for dark-field imaging.

We derive a reconstruction algorithm for refraction-contrast computed tomography (CT) using dark-field imaging (DFI) optics, which can extract refraction information by a single shot, from the ray equation in geometrical optics. The proposed algorithm is similar to the convolution reconstruction technique widely used in conventional CT. Thus, this algorithm can be implemented simply while also being fast and stable. To demonstrate its validity, we constructed the imaging system based on DFI optics composed of a transmission Laue-type angular analyzer at the vertical wiggler beamline BL-14C in KEK and performed a preliminary imaging experiment using a physical phantom to successfully obtain the DFI-CT image using the proposed algorithm.

Usefulness of X-ray dark-field imaging in the evaluation of local recurrence after nipple-sparing mastectomy.

PURPOSE: 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. METHODS: 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. 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. CONCLUSIONS: 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.

Ring artifact removal for differential phase-contrast X-ray computed tomography using a conditional generative adversarial network.

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.

X-ray Dark-Field Imaging (XDFI)-a Promising Tool for 3D Virtual Histopathology.

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.

Synchrotron-based scattered radiation from phantom materials used in X-ray CT.

Synchrotron-based scattered radiation form low-contrast phantom materials prepared from polyethylene, polystyrene, nylon, and Plexiglas is used as test objects in X-ray CT was examined with 8, 10 and 12 keV X-rays. These phantom materials of medical interest will contains varying proportions of low atomic number elements. The assessment will allowed us to estimate the fluorescence to total scattered radiation. Detected the fluorescence spectra and the associated scattered radiation from calcium hydroxyapatite phantom with 8, 10 and 12 keV synchrotron X-rays. Samples with Bonefil (60% and 70% of calcium hydroxyapatite) and Bone cream (35 approximately 45% of calcium hydroxyapatite), were used. Utilized the X-ray micro-spectroscopy beamline facility, X27A, available at NSLS, BNL, USA. The primary beam with a spot size of the order of approximately 10 mum, has been used for focusing. With this spatial resolution and high flux throuput, the synchrotron-based scattered radiation from the phantom materials were measured using a liquid-nitrogen-cooled 13-element energy-dispersive high-purity germanium detector.

X-ray dark-field phase-contrast imaging: Origins of the concept to practical implementation and applications.

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.

Improving contrast and spatial resolution in crystal analyzer-based x-ray dark-field imaging: Theoretical considerations and experimental demonstration.

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.

Cardiac fiber tracking on super high-resolution CT images: a comparative study.

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 ( µ CT ) is another commercially available imaging modality. Approach: We evaluate the usefulness of µ CT 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 µ CT volume caused incorrect tracking around the boundaries caused by stitching scanning. Conclusions: Our experimental results demonstrated that µ CT scanning can be used for cardiac fiber analysis, although further investigation is required in the differences of fiber analysis results on RCT and µ CT .

Imaging renal structures by X-ray phase-contrast microtomography.

X-ray crystal interferometer-based X-ray phase-contrast microtomography (phase-contrast microtomography) is able to image microstructures within soft tissue without the use of a contrast agent. Here we determined the feasibility of using this technique in the non-destructive inspection of formalin-fixed kidney tissue from certain hamsters that spontaneously develop mesangial thickening with focal and segmental glomerulosclerosis, and from age-matched Syrian hamsters. We used a triple Laue-case X-ray interferometer with a 40 microm-thick analyzer, a sample cell, and an X-ray charge-coupled-device camera with a 4.34 microm pixel size. Images of glomeruli and tubular structures were similar to those seen using 40-100 x magnification on an optical microscope. In samples from two female glomerulosclerotic hamsters, seven scattered lesions were detected. The wedge-shaped pathological lesions included mild atrophic tubular walls, markedly dilated tubular lumen, high-density glomeruli, and widening of Bowman's space. The microvasculature was distinctly visualized in the specimens without any contrast agents. Hence, phase-contrast microtomography can detect small scattered lesions in diseased kidney tissue and is a powerful auxiliary tool for pre-histological evaluations.

Depth-resolving THz imaging with tomosynthesis.

We demonstrated a depth-resolved 3D imaging technique based on absorption contrast using tomosynthesis. Tomosynthesis is similar to computed tomography except that the number of projections is much smaller. We constructed a tomosynthesis imaging system, which detects a transmitted continuous THz wave. We applied a backprojection method that was suitable for the constructed detection configuration, to reconstruct an image. Using this system, we imaged a test sample made from paper and reproduced characters written by pencil.

3-D reconstruction and virtual ductoscopy of high-grade ductal carcinoma in situ of the breast with casting type calcifications using refraction-based X-ray CT.

Stereomicroscopic observations of thick sections, or three-dimensional (3-D) reconstructions from serial sections, have provided insights into histopathology. However, they generally require time-consuming and laborious procedures. Recently, we have developed a new algorithm for refraction-based X-ray computed tomography (CT). The aim of this study is to apply this emerging technology to visualize the 3-D structure of a high-grade ductal carcinomas in situ (DCIS) of the breast. The high-resolution two-dimensional images of the refraction-based CT were validated by comparing them with the sequential histological sections. Without adding any contrast medium, the new CT showed strong contrast and was able to depict the non-calcified fine structures such as duct walls and intraductal carcinoma itself, both of which were barely visible in a conventional absorption-based CT. 3-D reconstruction and virtual endoscopy revealed that the high-grade DCIS was located within the dichotomatous branches of the ducts. Multiple calcifications occurred in the necrotic core of the continuous DCIS, resulting in linear and branching (casting type) calcifications, a hallmark of high-grade DCIS on mammograms. In conclusion, refraction-based X-ray CT approaches the low-power light microscopic view of the histological sections. It provides high quality slice data for 3-D reconstruction and virtual ductosocpy.