Correction to: Towards clinical grating-interferometry mammography.

The article Towards clinical grating-interferometry mammography, written by Carolina Arboleda, Zhentian Wang, Konstantins Jefimovs, Thomas Koehler, Udo Van Stevendaal, Norbert Kuhn, Bernd David, Sven Prevrhal, Kristina Lång, Serafino Forte, Rahel Antonia Kubik-Huch, Cornelia Leo.

Towards clinical grating-interferometry mammography.

OBJECTIVES: Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, as several research works have demonstrated in a pre-clinical setting, since it is able to provide attenuation, differential phase contrast, and scattering images simultaneously. In order to translate this technique to the clinics, it has to be adapted to cover a large field-of-view within a clinically acceptable exposure time and radiation dose. METHODS: We set up a grating interferometer that fits into a standard mammography system and fulfilled the aforementioned conditions. Here, we present the first mastectomy images acquired with this experimental device. RESULTS AND CONCLUSION: Our system performs at a mean glandular dose of 1.6 mGy for a 5-cm-thick, 18%-dense breast, and a field-of-view of 26 × 21 cm2. It seems to be well-suited as basis for a clinical-environment device. Further, dark-field signals seem to support an improved lesion visualization. Evidently, the effective impact of such indications must be evaluated and quantified within the context of a proper reader study. KEY POINTS: • Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, since it is sensitive to refraction and scattering and thus provides additional tissue information. • The most straightforward way to do grating-interferometry in the clinics is to modify a standard mammography device. • In a first approximation, the doses given with this technique seem to be similar to those of conventional mammography.

Experimental feasibility of spectral photon-counting computed tomography with two contrast agents for the detection of endoleaks following endovascular aortic repair.

OBJECTIVES: After endovascular aortic repair (EVAR), discrimination of endoleaks and intra-aneurysmatic calcifications within the aneurysm often requires multiphase computed tomography (CT). Spectral photon-counting CT (SPCCT) in combination with a two-contrast agent injection protocol may provide reliable detection of endoleaks with a single CT acquisition. METHODS: To evaluate the feasibility of SPCCT, the stent-lined compartment of an abdominal aortic aneurysm phantom was filled with a mixture of iodine and gadolinium mimicking enhanced blood. To represent endoleaks of different flow rates, the adjacent compartments contained either one of the contrast agents or calcium chloride to mimic intra-aneurysmatic calcifications. After data acquisition with a SPCCT prototype scanner with multi-energy bins, material decomposition was performed to generate iodine, gadolinium and calcium maps. RESULTS: In a conventional CT slice, Hounsfield units (HU) of the compartments were similar ranging from 147 to 168 HU. Material-specific maps differentiate the distributions within the compartments filled with iodine, gadolinium or calcium. CONCLUSION: SPCCT may replace multiphase CT to detect endoleaks without sacrificing diagnostic accuracy. It is a unique feature of our method to capture endoleak dynamics and allow reliable distinction from intra-aneurysmatic calcifications in a single scan, thereby enabling a significant reduction of radiation exposure. KEY POINTS: • SPCCT might enable advanced endoleak detection. • Material maps derived from SPCCT can differentiate iodine, gadolinium and calcium. • SPCCT may potentially reduce radiation burden for EVAR patients under post-interventional surveillance.

Evaluation of spectral photon counting computed tomography K-edge imaging for determination of gold nanoparticle biodistribution in vivo.

Spectral photon counting computed tomography (SPCCT) is an emerging medical imaging technology. SPCCT scanners record the energy of incident photons, which allows specific detection of contrast agents due to measurement of their characteristic X-ray attenuation profiles. This approach is known as K-edge imaging. Nanoparticles formed from elements such as gold, bismuth or ytterbium have been reported as potential contrast agents for SPCCT imaging. Furthermore, gold nanoparticles have many applications in medicine, such as adjuvants for radiotherapy and photothermal ablation. In particular, longitudinal imaging of the biodistribution of nanoparticles would be highly attractive for their clinical translation. We therefore studied the capabilities of a novel SPCCT scanner to quantify the biodistribution of gold nanoparticles in vivo. PEGylated gold nanoparticles were used. Phantom imaging showed that concentrations measured on gold images correlated well with known concentrations (slope = 0.94, intercept = 0.18, RMSE = 0.18, R2 = 0.99). The SPCCT system allowed repetitive and quick acquisitions in vivo, and follow-up of changes in the AuNP biodistribution over time. Measurements performed on gold images correlated with the inductively coupled plasma-optical emission spectrometry (ICP-OES) measurements in the organs of interest (slope = 0.77, intercept = 0.47, RMSE = 0.72, R2 = 0.93). TEM results were in agreement with the imaging and ICP-OES in that much higher concentrations of AuNPs were observed in the liver, spleen, bone marrow and lymph nodes (mainly in macrophages). In conclusion, we found that SPCCT can be used for repetitive and non-invasive determination of the biodistribution of gold nanoparticles in vivo.

Sensitivity-based optimization for the design of a grating interferometer for clinical X-ray phase contrast mammography.

An X-ray grating interferometer (GI) suitable for clinical mammography must comply with quite strict dose, scanning time and geometry limitations, while being able to detect tumors, microcalcifications and other abnormalities. Such a design task is not straightforward, since obtaining optimal phase-contrast and dark-field signals with clinically compatible doses and geometrical constraints is remarkably challenging. In this work, we present a wave propagation based optimization that uses the phase and dark-field sensitivities as figures of merit. This method was used to calculate the optimal interferometer designs for a commercial mammography setup. Its accuracy was validated by measuring the visibility of polycarbonate samples of different thicknesses on a Talbot-Lau interferometer installed on this device and considering some of the most common grating imperfections to be able to reproduce the experimental values. The optimization method outcomes indicate that small grating pitches are required to boost sensitivity in such a constrained setup and that there is a different optimal scenario for each signal type.

Spectral Photon-counting CT: Initial Experience with Dual-Contrast Agent K-Edge Colonography.

Purpose To investigate the feasibility of using spectral photon-counting computed tomography (CT) to differentiate between gadolinium-based and nonionic iodine-based contrast material in a colon phantom by using the characteristic k edge of gadolinium. Materials and Methods A custom-made colon phantom was filled with nonionic iodine-based contrast material, and a gadolinium-filled capsule representing a contrast material-enhanced polyp was positioned on the colon wall. The colon phantom was scanned with a preclinical spectral photon-counting CT system to obtain spectral and conventional data. By fully using the multibin spectral information, material decomposition was performed to generate iodine and gadolinium maps. Quantitative measurements were performed within the lumen and polyp to quantitatively determine the absolute content of iodine and gadolinium. Results In a conventional CT section, absorption values of both contrast agents were similar at approximately 110 HU. Contrast material maps clearly differentiated the distributions, with gadolinium solely in the polyp and iodine in the lumen of the colon. Quantitative measurements of contrast material concentrations in the colon and polyp matched well with those of actual prepared mixtures. Conclusion Dual-contrast spectral photon-counting CT colonography with iodine-filled lumen and gadolinium-tagged polyps may enable ready differentiation between polyps and tagged fecal material. © RSNA, 2016.

Slit-scanning differential x-ray phase-contrast mammography: proof-of-concept experimental studies.

PURPOSE: The purpose of this work is to investigate the feasibility of grating-based, differential phase-contrast, full-field digital mammography (FFDM) in terms of the requirements for field-of-view (FOV), mechanical stability, and scan time. METHODS: A rigid, actuator-free Talbot interferometric unit was designed and integrated into a state-of-the-art x-ray slit-scanning mammography system, namely, the Philips MicroDose L30 FFDM system. A dedicated phase-acquisition and phase retrieval method was developed and implemented that exploits the redundancy of the data acquisition inherent to the slit-scanning approach to image generation of the system. No modifications to the scan arm motion control were implemented. RESULTS: The authors achieve a FOV of 160 × 196 mm consisting of two disjoint areas measuring 77 × 196 mm with a gap of 6 mm between them. Typical scanning times vary between 10 and 15 s and dose levels are lower than typical FFDM doses for conventional scans with identical acquisition parameters due to the presence of the source-grating G0. Only minor to moderate artifacts are observed in the three reconstructed images, indicating that mechanical vibrations induced by other system components do not prevent the use of the platform for phase contrast imaging. CONCLUSIONS: To the best of our knowledge, this is the first attempt to integrate x-ray gratings hardware into a clinical mammography unit. The results demonstrate that a scanning differential phase contrast FFDM system that meets the requirements of FOV, stability, scan time, and dose can be build.

Clinical boundary conditions for grating-based differential phase-contrast mammography.

Research in grating-based differential phase-contrast imaging (DPCI) has gained increasing momentum in the past couple of years. The first results on the potential clinical benefits of the technique for X-ray mammography are becoming available and indicate improvements in terms of general image quality, the delineation of lesions versus the background tissue and the visibility of microcalcifications. In this paper, we investigate some aspects related to the technical feasibility of DPCI for human X-ray mammography. After a short introduction to state-of-the-art full-field digital mammography in terms of technical aspects as well as clinical aspects, we put together boundary conditions for DPCI. We then discuss the implications for system design in a comparative manner for systems with two-dimensional detectors versus slit-scanning systems, stating advantages and disadvantages of the two designs. Finally, focusing on a slit-scanning system, we outline a possible concept for phase acquisition.

A study on mastectomy samples to evaluate breast imaging quality and potential clinical relevance of differential phase contrast mammography.

OBJECTIVES: Differential phase contrast and scattering-based x-ray mammography has the potential to provide additional and complementary clinically relevant information compared with absorption-based mammography. The purpose of our study was to provide a first statistical evaluation of the imaging capabilities of the new technique compared with digital absorption mammography. MATERIALS AND METHODS: We investigated non-fixed mastectomy samples of 33 patients with invasive breast cancer, using grating-based differential phase contrast mammography (mammoDPC) with a conventional, low-brilliance x-ray tube. We simultaneously recorded absorption, differential phase contrast, and small-angle scattering signals that were combined into novel high-frequency-enhanced images with a dedicated image fusion algorithm. Six international, expert breast radiologists evaluated clinical digital and experimental mammograms in a 2-part blinded, prospective independent reader study. The results were statistically analyzed in terms of image quality and clinical relevance. RESULTS: The results of the comparison of mammoDPC with clinical digital mammography revealed the general quality of the images to be significantly superior (P < 0.001); sharpness, lesion delineation, as well as the general visibility of calcifications to be significantly more assessable (P < 0.001); and delineation of anatomic components of the specimens (surface structures) to be significantly sharper (P < 0.001). Spiculations were significantly better identified, and the overall clinically relevant information provided by mammoDPC was judged to be superior (P < 0.001). CONCLUSIONS: Our results demonstrate that complementary information provided by phase and scattering enhanced mammograms obtained with the mammoDPC approach deliver images of generally superior quality. This technique has the potential to improve radiological breast diagnostics.

The first analysis and clinical evaluation of native breast tissue using differential phase-contrast mammography.

OBJECTIVES: Phase-contrast and scattering-based x-ray imaging are known to provide additional and complementary information to conventional, absorption-based methods, and therefore have the potential to play a crucial role in medical diagnostics. We report on the first mammographic investigation of 5 native, that is, freshly dissected, breasts carried out with a grating interferometer and a conventional x-ray tube source. Four patients in this study had histopathologically proven invasive breast cancer. One male patient, without the presence of any malignant formations within the resected breast, was included as a control specimen. MATERIALS AND METHODS: We used a Talbot-Lau grating setup installed on a conventional, low-brilliance x-ray source; the interferometer operated at the fifth Talbot distance, at a tube voltage of 40 kVp with mean energy of 28 keV, and at a current of 25 mA. The device simultaneously recorded absorption, differential phase and small-angle scattering signals from the native breast tissue. These quantities were then combined into novel color- and high-frequency-enhanced radiographic images. Presurgical images (conventional mammography, ultrasonography, and magnetic resonance imaging) supported the findings and clinical relevance was verified. RESULTS: Our approach yields complementary and otherwise inaccessible information on the electron density distribution and the small-angle scattering power of the sample at the microscopic scale. This information can be used to potentially answer clinically relevant, yet unresolved questions such as unequivocally discerning between malignant and premalignant changes and postoperative scars and distinguishing cancer-invaded regions within healthy tissue. CONCLUSIONS: We present the first ex vivo images of fresh, native breast tissue obtained from mastectomy specimens using grating interferometry. This technique yields improved diagnostic capabilities when compared with conventional mammography, especially when discerning the type of malignant conversions and their breadth within normal breast tissue. These promising results advance us toward the ultimate goal, using grating interferometry in vivo on humans in a clinical setting.

Focal cystic high-attenuation lesions: characterization in renal phantom by using photon-counting spectral CT--improved differentiation of lesion composition.

PURPOSE: To evaluate the capability of spectral computed tomography (CT) to improve the characterization of cystic high-attenuation lesions in a renal phantom and to test the hypothesis that spectral CT will improve the differentiation of cystic renal lesions with high protein content and those that have undergone hemorrhage or malignant contrast-enhancing transformation. MATERIALS AND METHODS: A renal phantom that contained cystic lesions grouped in nonenhancing cyst and hemorrhage series and an iodine-enhancing series was developed. Spectral CT is based on new detector designs that may possess energy-sensitive photon-counting abilities, thereby facilitating the assessment of quantitative information about the elemental and molecular composition of tissue or contrast materials. Imaging of the renal phantom was performed with a prototype scanner at 20 mAs and 70 keV, allowing characterization of x-ray photons at 25-34, 34-39, 39-44, 44-49, 49-55, and more than 55 keV. Region of interest analysis was used to determine lesion attenuation values at various x-ray energies. Statistical analysis was performed to assess attenuation patterns and identify distinct levels of attenuation on the basis of curve regression analysis with analysis of variance tables. RESULTS: Spectral CT depicted linear clusters for the cyst (P < .001, R(2) > 0.940) and hemorrhage (P < .001, R(2) > 0.962) series without spectral overlap. A distinct linear attenuation profile without spectral overlap was also detected for the iodine-enhancing series (P < .001, R(2) > 0.964), with attenuation values attained in the 34-39-keV energy bin statistically identified as outliers (mean slope variation, >37%), corresponding with iodine k-edge effects at 33.2 keV. CONCLUSION: Spectral CT has the potential to enable distinct characterization of hyperattenuating fluids in a renal phantom by helping identify proteinaceous and hemorrhagic lesions through assessment of their distinct levels of attenuation as well as by revealing iodine-containing lesions through analysis of their specific k-edge discontinuities.