Bi-Directional X-Ray Phase-Contrast Mammography

Phase-contrast x-ray imaging is a promising improvement of conventional absorption-based mammography for early tumor detection. This potential has been demonstrated recently, utilizing structured gratings to obtain differential phase and dark-field scattering images. However, the inherently anisotropic imaging sensitivity of the proposed mono-directional approach yields only insufficient diagnostic information, and has low diagnostic sensitivity to highly oriented structures. To overcome these limitations, we present a two-directional x-ray phase-contrast mammography approach and demonstrate its advantages by applying it to a freshly dissected, cancerous mastectomy breast specimen. We illustrate that the two-directional scanning procedure overcomes the insufficient diagnostic value of a single scan, and reliably detects tumor structures, independently from their orientation within the breast. Our results indicate the indispensable diagnostic necessity and benefit of a multi-directional approach for x-ray phase-contrast mammography.     

Lung tumors on multimodal radiographs derived from grating-based X-ray imaging – A feasibility study

PurposeThe purpose of this study was to assess whether grating-based X-ray imaging may have a role in imaging of pulmonary nodules on radiographs.Materials and methodsA mouse lung containing multiple lung tumors was imaged using a small-animal scanner with a conventional X-ray source and a grating interferometer for phase-contrast imaging. We qualitatively compared the signal characteristics of lung nodules on transmission, dark-field and phase-contrast images. Furthermore, we quantitatively compared signal characteristics of lung tumors and the adjacent lung tissue and calculated the corresponding contrast-to-noise ratios.ResultsOf the 5 tumors visualized on the transmission image, 3/5 tumors were clearly visualized and 1 tumor was faintly visualized in the dark-field image as areas of decreased small angle scattering. In the phase-contrast images, 3/5 tumors were clearly visualized, while the remaining 2 tumors were faintly visualized by the phase-shift occurring at their edges. No additional tumors were visualized in either the dark-field or phase-contrast images. Compared to the adjacent lung tissue, lung tumors were characterized by a significant decrease in transmission signal (median 0.86 vs. 0.91, p = 0.04) and increase in dark-field signal (median 0.71 vs. 0.65, p = 0.04). Median contrast-to-noise ratios for the visualization of lung nodules were 4.4 for transmission images and 1.7 for dark-field images (p = 0.04).ConclusionLung nodules can be visualized on all three radiograph modalities derived from grating-based X-ray imaging. However, our initial data suggest that grating-based multimodal X-ray imaging does not increase the sensitivity of chest radiographs for the detection of lung nodules.     

Toward Clinically Compatible Phase-Contrast Mammography

Phase-contrast mammography using laboratory X-ray sources is a promising approach to overcome the relatively low sensitivity and specificity of clinical, absorption-based screening. Current research is mostly centered on identifying potential diagnostic benefits arising from phase-contrast and dark-field mammography and benchmarking the latter with conventional state-of-the-art imaging methods. So far, little effort has been made to adjust this novel imaging technique to clinical needs. In this article, we address the key points for a successful implementation to a clinical routine in the near future and present the very first dose-compatible and rapid scan-time phase-contrast mammograms of both a freshly dissected, cancer-bearing mastectomy specimen and a mammographic accreditation phantom.     

Imaging Liver Lesions Using Grating-Based Phase-Contrast Computed Tomography with Bi-Lateral Filter Post-Processing

X-ray phase-contrast imaging shows improved soft-tissue contrast compared to standard absorption-based X-ray imaging. Especially the grating-based method seems to be one promising candidate for clinical implementation due to its extendibility to standard laboratory X-ray sources. Therefore the purpose of our study was to evaluate the potential of grating-based phase-contrast computed tomography in combination with a novel bi-lateral denoising method for imaging of focal liver lesions in an ex vivo feasibility study. Our study shows that grating-based phase-contrast CT (PCCT) significantly increases the soft-tissue contrast in the ex vivo liver specimens. Combining the information of both signals – absorption and phase-contrast – the bi-lateral filtering leads to an improvement of lesion detectability and higher contrast-to-noise ratios. The normal and the pathological tissue can be clearly delineated and even internal structures of the pathological tissue can be visualized, being invisible in the absorption-based CT alone. Histopathology confirmed the presence of the corresponding findings in the analyzed tissue. The results give strong evidence for a sufficiently high contrast for different liver lesions using non-contrast-enhanced PCCT. Thus, ex vivo imaging of liver lesions is possible with a polychromatic X-ray source and at a spatial resolution of ∼100 µm. The post-processing with the novel bi-lateral denoising method improves the image quality by combining the information from the absorption and the phase-contrast images.     

Diffuse optical imaging and spectroscopy of the breast: a brief outline of history and perspectives

Breast cancer is the most common cancer among women in industrialized countries. At present, X-ray mammography is the gold standard for breast imaging, but has limitations, especially when dense breasts are imaged, as typically occurs in young women. Optical imaging can non-invasively provide information on tissue composition, structure and physiology that can be beneficially exploited for breast lesion detection and identification. In the last few decades optical breast imaging has been investigated, using different geometries (projection imaging and tomography) and measurement techniques (continuous wave, frequency resolved and time resolved approaches). Also, data analysis and display varies significantly, ranging from intensity images to maps of the optical properties (absorption and scattering), tissue composition, and physiological parameters (typically blood volume and oxygenation). This paper outlines the historical evolution of optical imaging and spectroscopy of the breast, highlighting potentialities and limitations, and presents an overview of the main applications and perspectives of the field.     

Promising techniques for breast cancer detection,diagnosis, and staging using non-ionizing radiation imaging techniques

Traditional imaging for the diagnosis and staging of breast cancer has relied on the tissue morphology of cancers in the background of normal patterns of fibroglandular breast tissue. X-ray mammography and ultrasound have been the primary modalities for the diagnosis and the work-up of breast cancer. New modalities have been validated including magnetic resonance imaging (MRI) and positron emission tomography (PET). New pulse sequences in MRI combined with contrast enhancement kinetic perfusion curves have greatly enhanced detection of mammographically occult cancers. New modalities on the horizon include optical imaging, exploiting again the differential perfusion properties of cancers in a background of normal glandular tissue. Even more specificity can be ach eved with the addition of ductal or intravenous introduction of optical probes specific to tumor associated antigens such as the HER-2/neu receptor in aggressive breast cancers. Quantum dots and other fluorescent dyes coupled to peptides or other probes will greatly enhance our ability to detect cancers earlier and without ionizing radiation.     

Methodological features of magnetic resonance imaging mammography

By studying 211 females by currently available radiation techniques, such as X-ray study, ultrasonography, and magnetic resonance imaging mammography (MRIM), the authors consider that the specificity of contrast-enhanced MRIM (CE MRIM) is greater than that of MRIM without administering magnetic resonance contrast agents (MRCA). CE MRIM reveals clinically suspicious early-stage breast lesions and defines the stage of a tumorous process, the patients being unexposed to ionizing irradiation. CE MRIM as an auxiliary technique becomes one of the most informative ones, particularly in girls, early reproductive-age females with developed glandular tissue, and pregnant females. In the authors' opinion, the total algorithm of a breast study in this group of patients in specialized medical centers where trained physicians work should differ from the generally accepted algorithm: instead of applying X-ray mammography (XRM) as a basic method of primary diagnosis, ultrasound mammography using Doppler color mapping, followed by MRIM or XRM should be employed.     

Visualizing Typical Features of Breast Fibroadenomas Using Phase-Contrast CT: An Ex-Vivo Study

Background

Fibroadenoma is the most common benign solid breast lesion type and a very common cause for histologic assessment. To justify a conservative therapy, a highly specific discrimination between fibroadenomas and other breast lesions is crucial. Phase-contrast imaging offers improved soft-tissue contrast and differentiability of fine structures combined with the potential of 3-dimensional imaging. In this study we assessed the potential of grating-based phase-contrast CT imaging for visualizing diagnostically relevant features of fibroadenomas.

Materials and Methods

Grating-based phase-contrast CT was performed on six ex-vivo formalin-fixed breast specimens containing a fibroadenoma and three samples containing benign changes that resemble fibroadenomas using Talbot Lau interferometry and a polychromatic X-ray source. Phase-contrast and simultaneously acquired absorption-based 3D-datasets were manually matched with corresponding histological slices. The visibility of diagnostically valuable features was assessed in comparison with histology as the gold-standard.

Results

In all cases, matching of grating-based phase-contrast CT images and histology was successfully completed. Grating-based phase-contrast CT showed greatly improved differentiation of fine structures and provided accurate depiction of strands of fibrous tissue within the fibroadenomas as well as of the diagnostically valuable dilated, branched ductuli of the fibroadenomas. A clear demarcation of tumor boundaries in all cases was provided by phase- but not absorption-contrast CT.

Conclusions

Pending successful translation of the technology to a clinical setting and considerable reduction of the required dose, the data presented here suggest that grating-based phase-contrast CT may be used as a supplementary non-invasive diagnostic tool in breast diagnostics. Phase-contrast CT may thus contribute to the reduction of false positive findings and reduce the recall and core biopsy rate in population-based screening. Phase-contrast CT may further be used to assist during histopathological workup, offering a 3D view of the tumor and helping to identify diagnostically valuable tissue sections within large tumors.     

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

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 mum 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.     

GEANT4 Monte Carlo simulations for virtual clinical trials in breast X-ray imaging: Proof of concept

Virtual clinical trials (VCT) are in-silico reproductions of medical examinations, which adopt digital models of patients and simulated devices. They are intended to produce clinically equivalent outcome data avoiding long execution times, ethical issues related to radiation induced risks and huge costs related to real clinical trials with a patient population. In this work, we present a platform for VCT in 2D and 3D X-ray breast imaging. The VCT platform uses Monte Carlo simulations based on the Geant4 toolkit and patient breast models derived from a cohort of high resolution dedicated breast CT (BCT) volume data sets. Projection images of the breast and three-dimensional glandular dose maps are generated for a given breast model, by simulating both 2D full-field digital mammography (DM) and 3D BCT examinations. Uncompressed voxelized breast models were derived from segmented patient images. Compressed versions of the digital breast phantoms for DM were generated using a previously published digital compression algorithm. The Monte Carlo simulation framework has the capability of generating and tracking ~10⁵ photons/s using a server equipped with 16-cores and 3.0 GHz clock speed. The VCT platform will provide a framework for scanner design optimization, comparison between different scanner designs and between different modalities or protocols on computational breast models, without the need for scanning actual patients as in conventional clinical trials.     

Normalized glandular dose coefficients in mammography,digital breast tomosynthesis and dedicated breast CT

PurposeTo provide mean glandular dose (MGD) estimates via Monte Carlo (MC) simulations as a function of the breast models and scan parameters in mammography, digital breast tomosynthesis (DBT) and dedicated breast CT (BCT).MethodsThe MC code was based on GEANT4 toolkit. The simulated compressed breast was either a cylinder with a semi-circular section or ad hoc shaped for oblique view (MLO). In DBT we studied the influence of breast models and exam parameters on the T-factors (i.e. the conversion factor for the calculation of the MGD in DBT from that for a 0-degree projection), and in BCT we investigated the influence on the MGD estimates of the ion chamber volume used for the air kerma measurements.ResultsIn mammography, a model representative of a breast undergoing an MLO view exam did not produce substantial differences (0.4%) in MGD estimates, when compared to a conventional cranio-caudal (CC) view breast model. The beam half value layer did not present a significant influence on T-factors in DBT (<0.8%), while the skin model presented significant influence on MGD estimates (up to 3.3% at 30 degrees scan angle), increasing for larger scan angles. We derived a correction factor for taking into account the different ion chamber volume used in MGD estimates in BCT.ConclusionsA series of MC code modules for MGD estimates in 2D and 3D breast imaging have been developed in order to take into account the most recent advances in breast models.     

Evaluation of the effect of silicone breast inserts on X-ray mammography and breast tomosynthesis images: A Monte Carlo simulation study

PurposeBreast augmentation is one of the most popular cosmetic surgeries worldwide. The aim of this study is to investigate the effect of breast implant insertion on the detectability and visibility of lesions on mammography and breast tomosynthesis (BT) images.Materials and methodsThree software phantoms, composed of a homogeneous background with embedded silicone gel structures, and two types of breast abnormalities, microcalcifications (µCs) and masses, were generated. Two X-ray breast imaging modalities were simulated: mammography and BT with six incident monochromatic X-ray beams with energies in the interval between 20 and 30 keV. Projection images were generated using an in-house developed Monte Carlo simulator. The detectability of mammographic findings adjacent to the implant material and the influence of the incident beam energy and implant thickness on the feature detection were studied.ResultsIt was found that implants thicker than 26 mm for the case of mammography and 14 mm for the case of BT obscured the visibility of underlying structures. Although BT demonstrated a lack of contrast, this modality was able to visualize µCs under considerable depths of implant. Increasing the incident beam energy led to better visualization of small µCs, while in the case of breast masses, their detectability was limited.ConclusionsSilicone gel implants introduce a limitation in the image quality of mammograms resulting in low detectability of features. In addition, silicone gel implants obscure partially or totally parts of the image, depending on the size and the thickness of the implant as well the energy of the X-rays used.     

High-resolution confocal imaging and three-dimensional rendering

Intrinsic opacity and inhomeogeniety of most biological tissues have prevented the efficient light penetration and signal detection for high-resolution confocal imaging of thick tissues. Here, we summarize recent technical advances in high-resolution confocal imaging for visualization of cellular structures and gene expression within intact whole-mount thick tissues. First, we introduce features of the FocusClear technology that render biological tissue transparent and thus improve the light penetration and signal detection. Next, a universal fluorescence staining method that labels all nuclei and membranes is described. We then demonstrate the postrecording image processing techniques for 3D visualization. From these images, regions of interest in the whole-mount brain can be segmented and volume rendered. Together, these technical advances in confocal microscopy allow visualization of structures within whole-mount tissues up to 1mm thick at a resolution similar to that of the observation of single cells in culture. Practical uses and limitations of these techniques are discussed.     

Characterization of the imaging settings in screening mammography using a tracking and reporting system: A multi-center and multi-vendor analysis

A tracking and reporting system was developed to monitor radiation dose in X-ray breast imaging. We used our tracking system to characterize and compare the mammographic practices of five breast imaging centers located in the United States and Brazil. Clinical data were acquired using eight mammography systems comprising three modalities: computed radiography (CR), full-field digital mammography (FFDM), and digital breast tomosynthesis (DBT). Our database consists of metadata extracted from 334,234 images. We analyzed distributions and correlations of compressed breast thickness (CBT), compression force, target-filter combinations, X-ray tube voltage, and average glandular dose (AGD). AGD reference curves were calculated based on AGD distributions as a function of CBT. These curves represent an AGD reference for a particular population and system. Differences in AGD and imaging settings were attributed to a combination of factors, such as improvements in technology, imaging protocol, and patient demographics. The tracking system allows the comparison of various imaging settings used in screening mammography, as well as the tracking of patient- and population-specific breast data collected from different populations.     

Development of high-sensitivity near-infrared fluorescence imaging device for early cancer detection

We have developed a high-sensitivity near-infrared (NIR) optical imaging system for noninvasive cancer detection based on the molecular-labeled fluorescent contrast agents. Recent developments in molecular beacons offer a way to selectively tag various precancer and cancer signatures and provide high tumor-to-background contrast. Near-infrared imaging can deeply probe tissue up to a couple of centimeters; thus, it possesses the potential for noninvasive detection of breast or lymph node cancer. A phase cancellation (in- and antiphase) device is used to increase the sensitivity in detecting fluorescent photons and the accuracy of tumor localization. The optoelectronic system consists of the laser diode sources, fiber optics, interference filter (to select the fluorescent photons), and the high-sensitivity photon detector (photomultiplier tube). The source-detector pair scans the tissue surface in multiple directions, and the localization image can be obtained by angular back-projection reconstruction. Simulations and experimental data demonstrated the feasibility of detection and localization offluorescent object embedded inside the highly scattering media. Tumor-bearing mouse model with injection of fluorescent contrast agents is used to simulate the human breast tumor labeled with molecular beacons. The system can detect fluorescent contrast agents as small as one nanomole at the depth of three centimeters, with a three-millimeter localization error. This instrument has the potential for tumor diagnosis and imaging, and the accuracy of the localization suggests that this system could help guide the clinical fine-needle biopsy. Also, this portable device would be complementary to x-ray mammography and provide add-on information on early diagnosis and localization of breast tumor.     

Mammographic measurements before and after augmentation mammaplasty

Thirty-five augmented women underwent mammography using both the standard implant-compression technique and, when possible, the implant-displacement technique; all had preaugmentation film-screen mammography available for evaluation. The area of mammographically visualized breast tissue before and after augmentation mammaplasty was measured using a transparent grid. Patients with subglandular implants had a mean decrease of 49 percent of measurable tissue area with compression mammography and a 39 percent decrease with displacement mammography. Patients with submuscular implants had a 28 percent decrease in measurable tissue area with compression mammography and a 9 percent decrease with displacement mammography. Anterior breast tissue was seen better with displacement mammography; posterior breast tissue, with compression mammography. Most patients had some degree of parenchymal scarring and lower image quality after augmentation. State-of-the-art mammography was not possible in most patients augmented with silicone-gel-filled implants.     

Hybrid framework for feasible modeling of an edge illumination X-ray phase-contrast imaging system at a human scale

Here, we present a hybrid approach for simulating an edge illumination X-ray phase-contrast imaging (EIXPCi) set-up using graphics processor units (GPU) with a high degree of accuracy. In this study, the applicability of pixel, mesh and non-uniform rational B-splines (NURBS) objects to carry out realistic maps of X-ray phase-contrast distribution at a human scale is accounted for by using numerical anthropomorphic phantoms and a very fast and robust simulation framework which integrates total interaction probabilities along selected X-ray paths. We exploit the mathematical and algorithmic properties of NURBS and describe how to represent human scale phantoms in an edge illumination X-ray phase-contrast model. The presented implementation allows the modeling of a variety of physical interactions of x-rays with different mathematically described objects and the recording of quantities, e.g. path integrals, interaction sites and deposited energies. Furthermore, our efficient, scalable and optimized hybrid Monte Carlo and ray-tracing projector can be used in iterative reconstruction algorithms on multi GPU heterogeneous systems. The preliminary results of our innovative approach show the fine performance of an edge illumination X-ray phase-contrast medical imaging system on various human-like soft tissues with noticeably reduced computation time. Our approach to the EIXPCi modeling confirms that building a true imaging system at a human scale should be possible and the simulations presented here aim at its future development.     

High-resolution gamma-camera for molecular breast imaging: First clinical results

Scintimair mography is a molecular breast imaging technique using tumour-seeking radiopharmaceuticals; with standard gamma-cameras, is proved of value especially when mammography is indeterminate and in women with dense breasts; nevertheless, this technique shows a high sensitivity only for cancers >1 cm. The issue of detecting small cancers is critical for the future development and clinical usefulness of breast imaging with radiopharmaceuticals, because other modalities are increasingly employed for early identification of small abnormalities. The use of high-resolution dedicated cameras for breast imaging is the best option to improve small cancers' detection: they allow greater flexibility in patient positioning, and the availability of projections similar to those of mammography. Moreover, the detector can be placed directly against the breast, and a mild compression is possible, with the results of reducing breast thickness, increasing the target-to-background ratio and the sensitivity. Our first clinical findings using the dedicased camera Lumagem 3200S (Gamma Medica, Inc., Northridge, USA) are very satisfactory. Till now, 29 patients with BI-RADS category III and IV lesions ≤1 cm were prospectively evaluated using a conventional gamma-camera and the dedicated device. Four out nine (44%) of the malignant lesions were detected with the standard gamma-camera, whereas the high-resolution camera visualized all the breast cancers. The standard gamma-camera and the dedicated one showed the same specificity: 19 out of 20 (95%) benign lesions were negative. Our results indicate that molecular breast imaging with this dedicated camera is able to detect small cancers in patients with probably benign or low-suspicion to indeterminate mammographic findings.     

Imaging of Metastatic Lymph Nodes by X-ray Phase-Contrast Micro-Tomography

Invasive cancer causes a change in density in the affected tissue, which can be visualized by x-ray phase-contrast tomography. However, the diagnostic value of this method has so far not been investigated in detail. Therefore, the purpose of this study was, in a blinded manner, to investigate whether malignancy could be revealed by non-invasive x-ray phase-contrast tomography in lymph nodes from breast cancer patients. Seventeen formalin-fixed paraffin-embedded lymph nodes from 10 female patients (age range 37–83 years) diagnosed with invasive ductal carcinomas were analyzed by X-ray phase-contrast tomography. Ten lymph nodes had metastatic deposits and 7 were benign. The phase-contrast images were analyzed according to standards for conventional CT images looking for characteristics usually only visible by pathological examinations. Histopathology was used as reference. The result of this study was that the diagnostic sensitivity of the image analysis for detecting malignancy was 100% and the specificity was 87%. The positive predictive value was 91% for detecting malignancy and the negative predictive value was 100%. We conclude that x-ray phase-contrast imaging can accurately detect density variations to obtain information regarding lymph node involvement previously inaccessible with standard absorption x-ray imaging.     

Approaches to improving breast cancer diagnosis using a high resolution,breast specific gamma camera

Mammography remains the gold standard in breast cancer detection, although there remains a challenge for improvement in sensitivity of breast cancer detection and diagnosis. Although mammography is the most frequently utilized examination to screen for breast cancer, which has resulted in a reduction of breast cancer mortality, still some cancers are unable to be visualized on mammographic images. Mammography films are interpreted using an anatomic approach. A new approach to breast cancer diagnosis utilizes a breast specific gamma camera to measure radiotracer uptake of abnormal tissue in the breast in patients with an abnormal mammogram or palpble mass using technetium sestamibi. Images are taken using the same positioning techniques as mammography for comparison of both types of images. Multi-Institutional trials using a traditional gamma camera demonstrated potential for this approach. However, the inability of traditional gamma camera intrinsic resolution and non-optinuized breast imaging limited scintimammography. Therefore, a breast specific, high resolution gamma camera was developed to overcome these limitations.Results of clinical studies evaluating BSGI are promising and are increasingly being used. Additionally, means for minimally invasive imaging-guided acquisition of tissue are being developed so that biopsies will be avaibles for areas of interest based on radiotracer uptake.Breast specific gamma camera nuclear imaging of the breast is a developing and increasingly utilized approach to improving breast cancer detection and diagnosis.