Accurate effective atomic number determination with polychromatic grating-based phase-contrast computed tomography.

The demand for quantitative medical imaging is increasing in the ongoing digitalization. Conventional computed tomography (CT) is energy-dependent and therefore of limited comparability. In contrast, dual-energy CT (DECT) allows for the determination of absolute image contrast quantities, namely the electron density and the effective atomic number, and is already established in clinical radiology and radiation therapy. Grating-based phase-contrast computed tomography (GBPC-CT) is an experimental X-ray technique that also allows for the measurement of the electron density and the effective atomic number. However, the determination of both quantities is challenging when dealing with polychromatic GBPC-CT setups. In this paper, we present how to calculate the effective atomic numbers with a polychromatic, laboratory GBPC-CT setup operating between 35 and 50\,kVp. First, we investigated the accuracy of the measurement of the attenuation coefficients and electron densities. For this, we performed a calibration using the concept of effective energy. With the reliable experimental quantitative values, we were able to evaluate the effective atomic numbers of the investigated materials using a method previously shown with monochromatic X-ray radiation. In detail, we first calculated the ratio of the electron density and attenuation coefficient, which were experimentally determined with our polychromatic GBPC-CT setup. Second, we compared this ratio with tabulated total attenuation cross sections from literature values to determine the effective atomic numbers. Thus, we were able to calculate two physical absolute quantities -- the electron density and effective atomic number -- that are in general independent of the specific experimental conditions like the X-ray beam spectrum or the setup design.

Analysis and correction of bias induced by phase stepping jitter in grating-based X-ray phase-contrast imaging.

Grating-based X-ray phase-contrast (gbPC) is an X-ray phase-contrast imaging method involving optical gratings that typically employs the Talbot self-imaging effect. X-ray phase contrast is known to provide significant benefits for biomedical imaging. To investigate these benefits for gbPC, a high-sensitivity gbPC micro-CT setup for small biological samples has been constructed. A gbPC projection measurement simultaneously retrieves the transmittance, differential-phase and dark-field modalities of a sample. Phase stepping, the most common gbPC acquisition technique, involves several acquisitions at different lateral positions of one of the gratings. The three modalities can then be retrieved by least-squares- or FFT-based methods. Unfortunately, increasing differential-phase sensitivity also leads to an increased magnitude of artifacts introduced during retrieval of the modalities from the phase-stepping data, which limits image quality. Most importantly, processing of phase-stepping data with incorrect stepping positions (i.e., spatial sampling jitter) can introduce artifacts to the modalities. Using data from the high-sensitivity gbPC setup, as well as simulations, we show that an artifact is introduced by the jitter which is correlated with the phase of the stepping curve. We present a theoretical explanation for this correlation by introducing small deviations to an equidistant sampling of a stepping curve and approximating the effect on the calculation of the three gbPC modalities with a first-order Taylor approximation. Finally, we present an algorithm for the detection and removal of these artifacts that exploits these correlations. We show that this algorithm is able to eliminate these artifacts without degrading true image information.

Hard X-ray phase-contrast tomography of non-homogeneous specimens: grating interferometry versus propagation-based imaging.

X-ray phase-contrast imaging is an effective approach to drastically increase the contrast and sensitivity of microtomographic techniques. Numerous approaches to depict the real part of the complex-valued refractive index of a specimen are nowadays available. A comparative study using experimental data from grating-based interferometry and propagation-based phase contrast combined with single-distance phase retrieval applied to a non-homogeneous sample is presented (acquired at beamline ID19-ESRF). It is shown that grating-based interferometry can handle density gradients in a superior manner. The study underlines the complementarity of the two techniques for practical applications.

AHA classification of coronary and carotid atherosclerotic plaques by grating-based phase-contrast computed tomography.

OBJECTIVES: To evaluate the potential of grating-based phase-contrast computed-tomography (gb-PCCT) to classify human carotid and coronary atherosclerotic plaques according to modified American Heart Association (AHA) criteria. METHODS: Experiments were carried out at a laboratory-based set-up consisting of X-ray tube (40 kVp), grating-interferometer and detector. Eighteen human carotid and coronary artery specimens were examined. Histopathology served as the standard of reference. Vessel cross-sections were classified as AHA lesion type I/II, III, IV/V, VI, VII or VIII plaques by two independent reviewers blinded to histopathology. Conservative measurements of diagnostic accuracies for the detection and differentiation of plaque types were evaluated. RESULTS: A total of 127 corresponding gb-PCCT/histopathology sections were analyzed. Based on histopathology, lesion type I/II was present in 12 (9.5 %), III in 18 (14.2 %), IV/V in 38 (29.9 %), VI in 16 (12.6 %), VII in 34 (26.8 %) and VIII in 9 (7.0 %) cross-sections. Sensitivity, specificity and positive and negative predictive value were ≥0.88 for most analyzed plaque types with a good level of agreement (Cohen's kappa = 0.90). Overall, results were better in carotid (kappa = 0.97) than in coronary arteries (kappa = 0.85). Inter-observer agreement was high with kappa = 0.85, p < 0.0001. CONCLUSIONS: These results indicate that gb-PCCT can reliably classify atherosclerotic plaques according to modified AHA criteria with excellent agreement to histopathology. KEY POINTS: • Different atherosclerotic plaque types display distinct morphological features in phase-contrast CT. • Phase-contrast CT can detect and differentiate AHA plaque types. • Calcifications caused streak artefacts and reduced sensitivity in type VI lesions. • Overall agreement was higher in carotid than in coronary arteries.

Regularized iterative integration combined with non-linear diffusion filtering for phase-contrast x-ray computed tomography.

Phase-contrast x-ray computed tomography has a high potential to become clinically implemented because of its complementarity to conventional absorption-contrast.In this study, we investigate noise-reducing but resolution-preserving analytical reconstruction methods to improve differential phase-contrast imaging. We apply the non-linear Perona-Malik filter on phase-contrast data prior or post filtered backprojected reconstruction. Secondly, the Hilbert kernel is replaced by regularized iterative integration followed by ramp filtered backprojection as used for absorption-contrast imaging. Combining the Perona-Malik filter with this integration algorithm allows to successfully reveal relevant sample features, quantitatively confirmed by significantly increased structural similarity indices and contrast-to-noise ratios. With this concept, phase-contrast imaging can be performed at considerably lower dose.

Quantitative differentiation of minimal-fat angiomyolipomas from renal cell carcinomas using grating-based x-ray phase-contrast computed tomography: An ex vivo study.

BACKGROUND: The differentiation of minimal-fat-or low-fat-angiomyolipomas from other renal lesions is clinically challenging in conventional computed tomography. In this work, we have assessed the potential of grating-based x-ray phase-contrast computed tomography (GBPC-CT) for visualization and quantitative differentiation of minimal-fat angiomyolipomas (mfAMLs) and oncocytomas from renal cell carcinomas (RCCs) on ex vivo renal samples. MATERIALS AND METHODS: Laboratory GBPC-CT was performed at 40 kVp on 28 ex vivo kidney specimens including five angiomyolipomas with three minimal-fat (mfAMLs) and two high-fat (hfAMLs) subtypes as well as three oncocytomas and 20 RCCs with eight clear cell (ccRCCs), seven papillary (pRCCs) and five chromophobe RCC (chrRCC) subtypes. Quantitative values of conventional Hounsfield units (HU) and phase-contrast Hounsfield units (HUp) were determined and histogram analysis was performed on GBPC-CT and grating-based attenuation-contrast computed tomography (GBAC-CT) slices for each specimen. For comparison, the same specimens were imaged at a 3T magnetic resonance imaging (MRI) scanner. RESULTS: We have successfully matched GBPC-CT images with clinical MRI and histology, as GBPC-CT presented with increased soft tissue contrast compared to absorption-based images. GBPC-CT images revealed a qualitative and quantitative difference between mfAML samples (58±4 HUp) and oncocytomas (44±10 HUp, p = 0.057) and RCCs (ccRCCs: 40±12 HUp, p = 0.012; pRCCs: 43±9 HUp, p = 0.017; chrRCCs: 40±7 HUp, p = 0.057) in contrast to corresponding laboratory attenuation-contrast CT and clinical MRI, although not all differences were statistically significant. Due to the heterogeneity and lower signal of oncocytomas, quantitative differentiation of the samples based on HUp or in combination with HUs was not possible. CONCLUSIONS: GBPC-CT allows quantitative differentiation of minimal-fat angiomyolipomas from pRCCs and ccRCCs in contrast to absorption-based imaging and clinical MRI.

Assessment of intraductal carcinoma in situ (DCIS) using grating-based X-ray phase-contrast CT at conventional X-ray sources: An experimental ex-vivo study.

BACKGROUND: The extent of intraductal carcinoma in situ (DCIS) is commonly underestimated due to the discontinuous growth and lack of microcalcifications. Specimen radiography has been established to reduce the rate of re-excision. However, the predictive value for margin assessment with conventional specimen radiography for DCIS is low. In this study we assessed the potential of grating-based phase-contrast computed tomography (GBPC-CT) at conventional X-ray sources for specimen tomography of DCIS containing samples. MATERIALS AND METHODS: GBPC-CT was performed on four ex-vivo breast specimens containing DCIS and invasive carcinoma of non-specific type. Phase-contrast and absorption-based datasets were manually matched with corresponding histological slices as the standard of reference. RESULTS: Matching of CT images and histology was successful. GBPC-CT showed an improved soft tissue contrast compared to absorption-based images revealing more histological details in the same sections. Non-calcifying DCIS exceeding the invasive tumor could be correlated to areas of dilated bright ducts around the tumor. CONCLUSIONS: GBPC-CT imaging at conventional X-ray sources offers improved depiction quality for the imaging of breast tissue samples compared to absorption-based imaging, allows the identification of diagnostically relevant tissue details, and provides full three-dimensional assessment of sample margins.

3D grating-based X-ray phase-contrast computed tomography for high-resolution quantitative assessment of cartilage: An experimental feasibility study with 3T MRI, 7T MRI and biomechanical correlation.

OBJECTIVE: Aim of this study was, to demonstrate the feasibility of high-resolution grating-based X-ray phase-contrast computed tomography (PCCT) for quantitative assessment of cartilage. MATERIALS AND METHODS: In an experimental setup, 12 osteochondral samples were harvested from n = 6 bovine knees (n = 2 each). From each knee, one cartilage sample was degraded using 2.5% Trypsin. In addition to PCCT and biomechanical cartilage stiffness measurements, 3T and 7T MRI was performed including MSME SE T2 and ME GE T2* mapping sequences for relaxationtime measurements. Paired t-tests and receiver operating characteristics (ROC) curves were used for statistical analyses. RESULTS: PCCT provided high-resolution images for improved morphological cartilage evaluation as compared to 3T and 7T MRI. Quantitative analyses revealed significant differences between the superficial and the deep cartilage layer for T2 mapping as well as for PCCT (P<0.05). No significant difference was detected for PCCT between healthy and degraded samples (P>0.05). MRI and stiffness measurements showed significant differences between healthy and degraded osteochondral samples. Accuracy in the prediction of cartilage degradation was excellent for MRI and biomechanical analyses. CONCLUSION: In conclusion, high-resolution grating-based X-ray PCCT cartilage imaging is feasible. In addition to MRI and biomechanical analyses it provides complementary, water content independent, information for improved morphological and quantitative characterization of articular cartilage ultrastructure.

Qualitative and Quantitative Evaluation of Structural Myocardial Alterations by Grating-Based Phase-Contrast Computed Tomography.

OBJECTIVES: Grating-based phase-contrast computed tomography (gb-PCCT) relies on x-ray refraction instead of absorption to generate high-contrast images in biological soft tissue. The aim of this study was to evaluate the potential of gb-PCCT for the depiction of structural changes in heart disease. MATERIALS AND METHODS: Four human heart specimens from patients with hypertensive disease, ischemic disease, dilated heart disease, and cardiac lipomatosis were examined. The gb-PCCT setup consisted of an x-ray tube (40 kV, 70 mA), grating-interferometer, and detector, and allowed simultaneous acquisition of phase- and absorption-contrast data. With histopathology as the standard of reference, myocardium (MC), fibrotic scar (FS), interstitial fibrosis (IF), and fatty tissue (FT) were visually and quantitatively evaluated. Systematic differences in absorption- and phase-contrast Hounsfield units (HUabs and HUp) were assessed. RESULTS: Thirteen corresponding cross-sections were included, and MC, FS, IF, and FT were found in 13 (100%), 4 (30.8%), 7 (53.8%), and 13 (100%) cross-sections, respectively. Mean HUp/HUabs were 52.5/54.1, 86.6/69.7, 62.4/62.3, and -38.6/-258.9 for MC, FS, IF, and FT, respectively. An overlap in HUabs was observed for MC and IF (P = 0.84) but not for HUp (P < 0.01). Contrast-to-noise ratios were significantly higher in phase- than in absorption-contrast for MC/FT (35.4 vs 7.8; P < 0.01) and for MC/FS (12.3 vs 0.2; P < 0.01). CONCLUSIONS: Given its superior soft tissue contrast, gb-PCCT is able to depict structural changes in different cardiomyopathies, which can currently not be obtained by x-ray absorption-based imaging methods. If current technical limitations can be overcome, gb-PCCT may evolve as a powerful tool for the anatomical assessment of cardiomyopathy.

Tilted grating phase-contrast computed tomography using statistical iterative reconstruction.

Grating-based phase-contrast computed tomography (GBPC-CT) enables increased soft tissue differentiation, but often suffers from streak artifacts when performing high-sensitivity GBPC-CT of biomedical samples. Current GBPC-CT setups consist of one-dimensional gratings and hence allow to measure only the differential phase-contrast (DPC) signal perpendicular to the direction of the grating lines. Having access to the full two-dimensional DPC signal can strongly reduce streak artefacts showing up as characteristic horizontal lines in the reconstructed images. GBPC-CT with gratings tilted by 45° around the optical axis, combining opposed projections, and reconstructing with filtered backprojection is one method to retrieve the full three-dimensional DPC signal. This approach improves the quality of the tomographic data as already demonstrated at a synchrotron facility. However, additional processing and interpolation is necessary, and the approach fails when dealing with cone-beam geometry setups. In this work, we employ the tilted grating configuration with a laboratory GBPC-CT setup with cone-beam geometry and use statistical iterative reconstruction (SIR) with a forward model accounting for diagonal grating alignment. Our results show a strong reduction of streak artefacts and significant increase in image quality. In contrast to the prior approach our proposed method can be used in a laboratory environment due to its cone-beam compatibility.

Revising the lower statistical limit of x-ray grating-based phase-contrast computed tomography.

Phase-contrast x-ray computed tomography (PCCT) is currently investigated as an interesting extension of conventional CT, providing high soft-tissue contrast even if examining weakly absorbing specimen. Until now, the potential for dose reduction was thought to be limited compared to attenuation CT, since meaningful phase retrieval fails for scans with very low photon counts when using the conventional phase retrieval method via phase stepping. In this work, we examine the statistical behaviour of the reverse projection method, an alternative phase retrieval approach and compare the results to the conventional phase retrieval technique. We investigate the noise levels in the projections as well as the image quality and quantitative accuracy of the reconstructed tomographic volumes. The results of our study show that this method performs better in a low-dose scenario than the conventional phase retrieval approach, resulting in lower noise levels, enhanced image quality and more accurate quantitative values. Overall, we demonstrate that the lower statistical limit of the phase stepping procedure as proposed by recent literature does not apply to this alternative phase retrieval technique. However, further development is necessary to overcome experimental challenges posed by this method which would enable mainstream or even clinical application of PCCT.

Ex vivo characterization of pathologic fluids with quantitative phase-contrast computed tomography.

PURPOSE: X-ray phase-contrast imaging (PCI) provides additional information beyond absorption characteristics by detecting the phase shift of the X-ray beam passing through material. The grating-based system works with standard polychromatic X-ray sources, promising a possible clinical implementation. PCI has been shown to provide additional information in soft-tissue samples. The aim of this study was to determine if ex vivo quantitative phase-contrast computed tomography (PCCT) may differentiate between pathologic fluid collections. MATERIALS AND METHODS: PCCT was performed with the grating interferometry method. A protein serial dilution, human blood samples and 17 clinical samples of pathologic fluid retentions were imaged and correlated with clinical chemistry measurements. Conventional and phase-contrast tomography images were reconstructed. Phase-contrast Hounsfield Units (HUp) were used for quantitative analysis analogously to conventional HU. The imaging was analyzed using overall means, ROI values as well as whole-volume-histograms and vertical gradients. Contrast to noise ratios were calculated between different probes and between imaging methods. RESULTS: HUp showed a very good linear correlation with protein concentration in vitro. In clinical samples, HUp correlated rather well with cell count and triglyceride content. PCI was better than absorption imaging at differentiating protein concentrations in the protein samples as well as at differentiating blood plasma from cellular components. PCI also allowed for differentiation of watery samples (such as lymphoceles) from pus. CONCLUSION: Phase-contrast computed tomography is a promising tool for the differentiation of pathologic fluids that appear homogenous with conventional attenuation imaging.

Dark-field imaging in coronary atherosclerosis.

OBJECTIVES: Dark-field imaging based on small angle X-ray scattering has been shown to be highly sensitive for microcalcifications, e.g. in breast tissue. We hypothesized (i) that high signal areas in dark-field imaging of atherosclerotic plaque are associated with microcalcifications and (ii) that dark-field imaging is more sensitive for microcalcifications than attenuation-based imaging. METHODS: Fifteen coronary artery specimens were examined at an experimental set-up consisting of X-ray tube (40kV), grating-interferometer and detector. Tomographic dark-field-, attenuation-, and phase-contrast data were simultaneously acquired. Histopathology served as standard of reference. To explore the potential of dark field imaging in a full-body CT system, simulations were carried out with spherical calcifications of different sizes to simulate small and intermediate microcalcifications. RESULTS: Microcalcifications were present in 10/10 (100%) cross-sections with high dark-field signal and without evidence of calcifications in attenuation- or phase contrast. In positive controls with high signal areas in all three modalities, 10/10 (100%) cross-sections showed macrocalcifications. In negative controls without high signal areas, no calcifications were detected. Simulations showed that the microcalcifications generate substantially higher dark-field than attenuation signal. CONCLUSIONS: Dark-field imaging is highly sensitive for microcalcifications in coronary atherosclerotic plaque and might provide complementary information in the assessment of plaque instability.

Qualitative and Quantitative Imaging Evaluation of Renal Cell Carcinoma Subtypes with Grating-based X-ray Phase-contrast CT.

Current clinical imaging methods face limitations in the detection and correct characterization of different subtypes of renal cell carcinoma (RCC), while these are important for therapy and prognosis. The present study evaluates the potential of grating-based X-ray phase-contrast computed tomography (gbPC-CT) for visualization and characterization of human RCC subtypes. The imaging results for 23 ex vivo formalin-fixed human kidney specimens obtained with phase-contrast CT were compared to the results of the absorption-based CT (gbCT), clinical CT and a 3T MRI and validated using histology. Regions of interest were placed on each specimen for quantitative evaluation. Qualitative and quantitative gbPC-CT imaging could significantly discriminate between normal kidney cortex (54 ± 4 HUp) and clear cell (42 ± 10), papillary (43 ± 6) and chromophobe RCCs (39 ± 7), p < 0.05 respectively. The sensitivity for detection of tumor areas was 100%, 50% and 40% for gbPC-CT, gbCT and clinical CT, respectively. RCC architecture like fibrous strands, pseudocapsules, necrosis or hyalinization was depicted clearly in gbPC-CT and was not equally well visualized in gbCT, clinical CT and MRI. The results show that gbPC-CT enables improved discrimination of normal kidney parenchyma and tumorous tissues as well as different soft-tissue components of RCCs without the use of contrast media.

Quantitative Three-Dimensional Imaging of Lipid, Protein, and Water Contents via X-Ray Phase-Contrast Tomography.

X-ray phase-contrast computed tomography is an emerging imaging technology with powerful capabilities for three-dimensional (3D) visualization of weakly absorbing objects such as biological soft tissues. This technique is an extension of existing X-ray applications because conventional attenuation-contrast images are simultaneously acquired. The complementary information provided by both the contrast modalities suggests that enhanced material characterization is possible when performing combined data analysis. In this study, we describe how protein, lipid, and water concentrations in each 3D voxel can be quantified by vector decomposition. Experimental results of dairy products, porcine fat and rind, and different human soft tissue types are presented. The results demonstrate the potential of phase-contrast imaging as a new analysis tool. The 3D representations of protein, lipid, and water contents open up new opportunities in the fields of biology, medicine, and food science.

Experimental Realisation of High-sensitivity Laboratory X-ray Grating-based Phase-contrast Computed Tomography.

The possibility to perform high-sensitivity X-ray phase-contrast imaging with laboratory grating-based phase-contrast computed tomography (gbPC-CT) setups is of great interest for a broad range of high-resolution biomedical applications. However, achieving high sensitivity with laboratory gbPC-CT setups still poses a challenge because several factors such as the reduced flux, the polychromaticity of the spectrum, and the limited coherence of the X-ray source reduce the performance of laboratory gbPC-CT in comparison to gbPC-CT at synchrotron facilities. In this work, we present our laboratory X-ray Talbot-Lau interferometry setup operating at 40 kVp and describe how we achieve the high sensitivity yet unrivalled by any other laboratory X-ray phase-contrast technique. We provide the angular sensitivity expressed via the minimum resolvable refraction angle both in theory and experiment, and compare our data with other differential phase-contrast setups. Furthermore, we show that the good stability of our high-sensitivity setup allows for tomographic scans, by which even the electron density can be retrieved quantitatively as has been demonstrated in several preclinical studies.

Phase-Contrast Hounsfield Units of Fixated and Non-Fixated Soft-Tissue Samples.

X-ray phase-contrast imaging is a novel technology that achieves high soft-tissue contrast. Although its clinical impact is still under investigation, the technique may potentially improve clinical diagnostics. In conventional attenuation-based X-ray computed tomography, radiological diagnostics are quantified by Hounsfield units. Corresponding Hounsfield units for phase-contrast imaging have been recently introduced, enabling a setup-independent comparison and standardized interpretation of imaging results. Thus far, the experimental values of few tissue types have been reported; these values have been determined from fixated tissue samples. This study presents phase-contrast Hounsfield units for various types of non-fixated human soft tissues. A large variety of tissue specimens ranging from adipose, muscle and connective tissues to liver, kidney and pancreas tissues were imaged by a grating interferometer with a rotating-anode X-ray tube and a photon-counting detector. Furthermore, we investigated the effects of formalin fixation on the quantitative phase-contrast imaging results.

X-ray phase-contrast computed tomography of human coronary arteries.

OBJECTIVE: The objective of this study was to assess the potential of grating-based phase-contrast computed tomography (gb-PCCT) for the detection and characterization of human coronary artery disease in an experimental ex vivo validation study. MATERIALS AND METHODS: The study was approved by the institutional review board, and informed consent was obtained from all patients. Specimens were examined using a conventional low-coherence x-ray tube (40 kV) and a Talbot-Lau grating interferometer. Histopathologic assessment was used as the standard of reference. Signal characteristics of calcified, fibrous (FIB), and lipid-rich (LIP) tissue were visually and quantitatively assessed by phase-contrast Hounsfield units (HU). Conventional absorption-based HU values were also measured. Conservative measurements of diagnostic accuracy for the detection and differentiation of plaque components as well as quantitative measurements of vessel dimensions were obtained, and receiver operating characteristic curve analysis for plaque differentiation was performed. RESULTS: A total of 15 coronary arteries from 5 subjects were available for analysis (386 sections). Calcified, FIB, and LIP displayed distinct gb-PCCT signal criteria. The diagnostic accuracy of gb-PCCT was high with sensitivity, specificity, and negative and positive predictive values of 0.89 or greater for all plaque components with good interrater agreement (к ≥ 0.88). In addition, quantitative measurements of vessel dimensions in gb-PCCT were strongly correlated with measurements obtained from histopathology (Pearson R ≥ 0.86). Finally, phase-contrast Hounsfield units were superior to conventional HU in differentiating FIB and LIP (receiver operating characteristic analysis, 0.86 vs. 0.77, respectively; P < 0.05). CONCLUSIONS: In an ex vivo setting, gb-PCCT provides improved differentiation and quantification of coronary atherosclerotic plaque and may thus serve as a tool for nondestructive histopathology.

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.

FMT-PCCT: hybrid fluorescence molecular tomography-x-ray phase-contrast CT imaging of mouse models.

The implementation of hybrid fluorescence molecular tomography (FMT) and X-ray computed tomography (CT) has been shown to be a necessary development, not only for combining anatomical with functional and molecular contrast, but also for generating optical images of high accuracy. FMT affords highly sensitive 3-D imaging of fluorescence bio-distribution, but in stand-alone form it offers images of low resolution. It was shown that FMT accuracy significantly improves by considering anatomical priors from CT. Conversely, CT generally suffers from low soft tissue contrast. Therefore utilization of CT data as prior information in FMT inversion is challenging when different internal organs are not clearly differentiated. Instead, we combined herein FMT with emerging X-ray phase-contrast CT (PCCT). PCCT relies on phase shift differences in tissue to achieve soft tissue contrast superior to conventional CT. We demonstrate for the first time FMT-PCCT imaging of different animal models, where FMT and PCCT scans were performed in vivo and ex vivo, respectively. The results show that FMT-PCCT expands the potential of FMT in imaging lesions with otherwise low or no CT contrast, while retaining the cost benefits of CT and simplicity of hybrid device realizations. The results point to the most accurate FMT performance to date.