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.

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.

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.

Total liver fat quantification using three-dimensional respiratory self-navigated MRI sequence.

PURPOSE: MRI can produce quantitative liver fat fraction (FF) maps noninvasively, which can help to improve diagnoses of fatty liver diseases. However, most sequences acquire several two-dimensional (2D) slices during one or more breath-holds, which may be difficult for patients with limited breath-holding capacity. A whole-liver 3D FF map could also be obtained in a single acquisition by applying a reliable breathing-motion correction method. Several correction techniques are available for 3D imaging, but they use external devices, interrupt acquisition, or jeopardize the spatial resolution. To overcome these issues, a proof-of-concept study introducing a self-navigated 3D three-point Dixon sequence is presented here. METHODS: A respiratory self-gating strategy acquiring a center k-space profile was integrated into a three-point Dixon sequence. We obtained 3D FF maps from a water-fat emulsions phantom and fifteen volunteers. This sequence was compared with multi-2D breath-hold and 3D free-breathing approaches. RESULTS: Our 3D three-point Dixon self-navigated sequence could correct for respiratory-motion artifacts and provided more precise FF measurements than breath-hold multi-2D and 3D free-breathing techniques. CONCLUSION: Our 3D respiratory self-gating fat quantification sequence could correct for respiratory motion artifacts and yield more-precise FF measurements. Magn Reson Med 76:1400-1409, 2016. © 2015 International Society for Magnetic Resonance in Medicine.

Tilted-grating approach for scanning-mode X-ray phase contrast imaging.

Among the existent X-ray phase-contrast modalities, grating interferometry appears as a very promising technique for commercial applications, since it is compatible with conventional X-ray tubes and is robust from a mechanical point of view. However, since applications such as medical imaging and homeland security demand covering a considerable field of view, the fabrication of large-area gratings, which is known to be challenging and expensive, would be needed. A scanning setup is a good solution for this issue, because it uses cheaper line instead of large-area 2D detectors and, therefore, would require smaller gratings. In such a setup, the phase-retrieval using the conventional phase-stepping approach would be very slow, so having a faster method to record the signals becomes fundamental. To tackle this problem, we present a scanning-mode grating interferometer design, in which a grating is tilted to form Moiré fringes perpendicular to the grating lines. The sample is then translated along the fringes, so each line detector records a different phase step for each slice of the sample. This new approach was tested both in a simulated scenario and in an experimental setting, and its performance was quantitatively satisfactory compared to the traditional phase-stepping method and another existing scanning-mode technique.

Wavelet-based noise-model driven denoising algorithm for differential phase contrast mammography.

Traditional mammography can be positively complemented by phase contrast and scattering x-ray imaging, because they can detect subtle differences in the electron density of a material and measure the local small-angle scattering power generated by the microscopic density fluctuations in the specimen, respectively. The grating-based x-ray interferometry technique can produce absorption, differential phase contrast (DPC) and scattering signals of the sample, in parallel, and works well with conventional X-ray sources; thus, it constitutes a promising method for more reliable breast cancer screening and diagnosis. Recently, our team proved that this novel technology can provide images superior to conventional mammography. This new technology was used to image whole native breast samples directly after mastectomy. The images acquired show high potential, but the noise level associated to the DPC and scattering signals is significant, so it is necessary to remove it in order to improve image quality and visualization. The noise models of the three signals have been investigated and the noise variance can be computed. In this work, a wavelet-based denoising algorithm using these noise models is proposed. It was evaluated with both simulated and experimental mammography data. The outcomes demonstrated that our method offers a good denoising quality, while simultaneously preserving the edges and important structural features. Therefore, it can help improve diagnosis and implement further post-processing techniques such as fusion of the three signals acquired.

Fabrication of X-ray Gratings for Interferometric Imaging by Conformal Seedless Gold Electroplating.

We present a method to produce small pitch gratings for X-ray interferometric imaging applications, allowing the phase sensitivity to be increased and/or the length of the laboratory setup to be minimized. The method is based on fabrication of high aspect ratio silicon microstructures using deep reactive ion etching (Bosch technique) of dense grating arrays and followed by conformal electroplating of Au. We demonstrated that low resistivity Si substrates (<0.01 Ohm·cm) enable the metal seeding layer deposition step to be avoided, which is normally required to initiate the electroplating process. Etching conditions were optimized to realize Si recess structures with a slight bottom tapering, which ensured the void-free Au filling of the trenches. Vapor HF was used to remove the native oxide layer from the Si grating surface prior to electroplating in the cyanide-based Au electrolyte. Fabrication of Au gratings with pitch in the range 1.2-3.0 µm was successfully realized. A substantial improved aspect ratio of 45:1 for a pitch size of 1.2 µm was achieved with respect to the prior art on 4-inch wafer-based technology. The fabricated Au gratings were tested with X-ray interferometers in Talbot-Laue configuration with measured visibility of 13% at an X-ray design energy of 26 keV.

The trigonometric orthogonality of phase-stepping curves in grating-based x-ray phase-contrast imaging: Integral property and its implications for noise optimization.

PURPOSE: Grating-based x-ray phase-contrast imaging (GPCI) is a promising technique for clinical applications as it can provide two newly emerging imaging modalities (differential phase-contrast and dark-field contrast) in addition to the conventional absorption contrast. As far, phase-stepping strategy is the most commonly used approach in GPCI to indirectly acquire differential phase-contrast and dark-field contrast. It is known that the obtained phase-stepping curves (PSCs) have the cosine property and the convolution property, leading to two types of information retrieval approaches in literature: the Fourier component analysis and the multi-order moment analysis. The purpose of this paper is to derive a new property of PSCs and apply the property to noise optimization for information retrieval. METHODS: Based on the cosine expression of the flat PSC without the sample and the well-established convolution relationship between the flat PSC and the sample PSC, we reveal an important integral property of PSCs: the inner product of PSCs and an arbitrary function contains only zero-order and first-order components in the Fourier series. Furthermore, we apply the property to the direct multi-order moment analysis and propose a set of generalized forms including an optimal one in the presence of noise. RESULTS: To validate the effectiveness of our analysis, we compared the simulated and real experiment results retrieved by the original direct multi-order moment analysis with the ones retrieved by our proposed noise-optimal form. A significant improvement of noise performance by our method is observed and the improvement ratio in differential phase-contrast is consistent with our theoretical calculation (39.2%). CONCLUSIONS: In this paper, we reveal a new integral property of the acquired PSCs with and without samples in GPCI, which can be applied to information retrieval approaches like the direct multi-order moment analysis. Then we optimize these approaches to improve the noise performance, offering great potentials of dose reduction in practical applications.

Can grating interferometry-based mammography discriminate benign from malignant microcalcifications in fresh biopsy samples?

PURPOSE: In addition to absorption imaging, grating interferometry-based mammography (GIM) is capable of detecting differential-phase and scattering signals. In particular, the scattering signal can enable a quantifiable characterization of breast lesions. The purpose of this study was to determine if suspicious microcalcifications associated with benign or malignant lesions can be discriminated based on their absorption and scattering properties. MATERIALS AND METHODS: In this prospective, ethically approved study, 62 patients (mean age 60 y, range 39-89) with suspicious microcalcifications, who underwent stereotactic biopsies, were included. Biopsies were measured with an experimental GIM device and the ratios of the scattering and absorption signal (R-value) for microcalcifications were calculated. The mean R-values for benign and malignant lesions associated with microcalcifications were compared with the final histopathological diagnosis using a t-test. RESULTS: Twenty of the 62 participants had microcalcifications associated with malignancy. Comparing the two largest histopathological sub-groups of fibrosis (n = 23) vs. ductal carcinoma in situ (n = 15) resulted in an average R-value of 4.08 for benign and 2.80 for malignant lesions; p = 0.07. All microcalcifications associated with malignancy had an R-value below 4.71. Excluding microcalcifications with an R-value above this threshold would result in an 11 % reduction of false positives. CONCLUSION: The novel GIM modality has the potential to non-invasively characterize microcalcifications and might aid in the discrimination of benign from malignant lesions in fresh biopsy samples.

Microbubbles as a contrast agent in grating interferometry mammography: an ex vivo proof-of-mechanism study.

Grating interferometry mammography (GIM) is an experimental breast imaging method at the edge of being clinically implemented. Besides attenuation, GIM can measure the refraction and scattering of x-rays resulting in differential phase contrast (DPC) and dark-field (DF) images. In this exploratory study, we assessed the feasibility of using microbubbles as a contrast agent in GIM. Two millilitres of microbubbles and iodine were respectively injected into ex vivo breast phantoms, consisting of fresh chicken breasts. Native and postcontrast images were acquired with a clinically compatible GIM setup, operated at 38 kVp, 14-s acquisition time, and with a dose of 1.3 mGy. The visibility of the contrast agents was analysed in a side-by-side comparison by three radiologists. The contrast-to-noise-ratio (CNR) was calculated for each contrast agent. We found that both contrast agents were judged to be visible by the readers. The mean CNR was 3.1 ± 1.9 for microbubbles in DF and 24.2 ± 6.5 for iodine in attenuation. In conclusion, this is a first proof-of-mechanism study that microbubbles could be used as a contrast agent in clinically compatible GIM, due to their scattering properties, which implies the potential use of a contrast agent with a high safety profile in x-ray-based breast imaging.

Elimination of bisphenol a and triclosan using the enzymatic system of autochthonous colombian forest fungi.

Bisphenol A (BPA) and triclosan (TCS) are known or suspected potential endocrine disrupting chemicals (EDCs) which may pose a risk to human health and have an environmental impact. Enzyme preparations containing mainly laccases, obtained from Ganoderma stipitatum and Lentinus swartzii, two autochthonous Colombian forest white rot fungi (WRF), previously identified as high enzyme producers, were used to remove BPA and TCS from aqueous solutions. A Box-Behnken factorial design showed that pH, temperature, and duration of treatment were significant model terms for the elimination of BPA and TCS. Our results demonstrated that these EDCs were extensively removed from 5 mg L(-1) solutions after a contact time of 6 hours. Ninety-four percent of TCS and 97.8% of BPA were removed with the enzyme solution from G. stipitatum; 83.2% of TCS and 88.2% of BPA were removed with the L. swartzii enzyme solution. After a 6-hour treatment with enzymes from G. stipitatum and L. swartzii, up to 90% of the estrogenic activity of BPA was lost, as shown by the yeast estrogen screen assay. 2,2-Azino-bis-(3-ethylthiazoline-6-sulfonate) (ABTS) was used as a mediator (laccase/mediator system) and significantly improved the laccase catalyzed elimination of BPA and TCS. The elimination of BPA in the absence of a mediator resulted in production of oligomers of molecular weights of 454, 680, and 906 amu as determined by mass spectra analysis. The elimination of TCS in the same conditions produced dimers, trimers, and tetramers of molecular weights of 574, 859, and 1146 amu. Ecotoxicological studies using Daphnia pulex to determine lethal concentration (LC50) showed an important reduction of the toxicity of BPA and TCS solutions after enzymatic treatments. Use of laccases emerges thus as a key alternative in the development of innovative wastewater treatment technologies. Moreover, the exploitation of local biodiversity appears as a potentially promising approach for identifying new efficient strains for biotechnological applications.

In vitro anti-HIV-1 activity of the enzymatic extract enriched with laccase produced by the fungi Ganoderma sp. and Lentinus sp / Actividad anti-VIH-1 in vitro del extracto enzimático enriquecido con lacasa producido por los hongos Ganoderma sp. y Lentinus sp

Background: Natural compounds are a good source for the development of antiretroviral drugs with low cytotoxicity. The laccase enzyme, produced by fungi of the genera Ganoderma sp. and Lentinus sp., inhibits the reverse transcriptase (RT) of the human immunodeficiency virus 1 (HIV-1), in cell-free models in vitro. Objetives: In this study we evaluated the anti-HIV-1 activity of the enzymatic extracts (EE) enriched with laccase, produced by two native species of fungi of the same genera in an in vitro cell culture model. Methods: The inhibition of viral replication was performed using the U373-MAGI cell line infected with recombinant viruses in the presence/absence of the EE and 48 hpi, the percentage of infected cells was evaluated by flow cytometry for green fluorescent protein ­GFP­ and ELISA for p24. The inhibition of the RT was determined by quantification of early and late products of reverse transcription using quantitative PCR. Results: The EEs from Ganoderma sp. and Lentinus sp. inhibited the replication of HIV-1 between 80 and 90% and decreased the production of early and late transcripts between 55,5%-91,3% and 82,1%-93,6% respectively. The EE from Lentinus sp. had the best selectivity index (SI: 8.3). Conclusions: These results suggest the potential anti-HIV-1 activity of the EE for the exploration of an alternative therapy against HIV-1 infection.

Antecedentes: Los compuestos naturales son una buena fuente para el desarrollo de fármacos antirretrovirales con baja citotoxicidad. La enzima lacasa, producida por hongos del género Ganoderma sp. y Lentinus sp., inhibe la transcriptasa reversa (TR) del virus de la inmunodeficiencia humana tipo 1 (VIH-1), en modelos in vitro, libres de células. Objetivos: En este estudio se evaluó la actividad anti-VIH-1 del extracto enzimático (EE) enriquecido con lacasa, producida por dos especies nativas de hongos de los mismos géneros en un modelo in vitro de cultivo celular. Métodos: La inhibición de la replicación viral se realizó usando la línea celular U373-MAGI infectada con virus recombinantes en la presencia/ ausencia del EE y 48 hpi, el porcentaje de células infectadas se evaluó mediante citometría de flujo para GFP y ELISA para p24. La inhibición de la TR se determinó mediante la cuantificación de los productos tempranos y tardíos de la transcripción reversa utilizando una PCR cuantitativa. Resultados: El EE de Ganoderma sp. y Lentinus sp. inhibió la replicación del VIH-1 entre el 80 y 90% y disminuyó la producción de transcriptos tempranos y tardíos entre el 55,5% -91,3% y 82,1% -93,6%, respectivamente. El EE de Lentinus sp. mostró el mejor índice de selectividad (IS: 8.3). Conclusiones: Estos resultados sugieren el potencial anti-VIH-1 del EE para la exploración de una terapia alternativa contra la infección por el VIH-1.

P300-based brain computer interface experimental setup.

A Brain-Computer interface (BCI) is a communication system that enables the generation of a control signal from brain signals such as sensorymotor rhythms and evoked potentials; therefore, it constitutes a novel communication option for people with severe motor disabilities (such as Amyotrophic Lateral Sclerosis patients). This paper presents the development of a P300-based BCI. This prototype uses a homemade six-channel electroencephalograph for the acquisition of the signals, and a visual stimulation matrix; since this matrix contains letters of the alphabet as well as images associated to them, it permits word-writing and the elaboration of messages with the images. To process the signals the software BCI2000 and MATLAB 7.0 were used. The latter was used to program three linear translation algorithms (Stepwise Linear Discriminant Analysis, Lineal Discriminant Analysis and Least Squares) to convert the brain signals into communication signals. These algorithms had a classification accuracy of 90.73 %, 95.75 % and 89.45 % respectively, when using raw data; and of 90.78%, 49.48 % and 53.9 %, when data was previously common-average filtered. The experimental setup was tested in ten healthy volunteers; 5 of them got a 100% success, 1 a 90% success, 2 an around 70% success and 2 a 50% success, in the online free-spelling tests.

Enzymatic transformation of crystalline structure of copolymer poly (ethylene-co-vinyl alcohol) (EVOH)

Changes in the crystalline structure of the copolymer poly(ethylene-co-vinyl alcohol) (EVOH) that occurs during the enzymatic fermentation system with the fungus Phanerochaete chrysosoporium were studied. This fungus has a powerful group of oxidative enzymes that had been used for several processes of environmental pollutants degradation. In order to use the enzymatic system of the fungus to improve degradation, films of the copolymer are inoculated and maintained in a solid state fermentation (SSF) system using as substrate a mixture of agroindustrial corn wastes with an initial humidity of 90 por ciento, during forty days. Analyses of the films were made at different times of fermentation. The effect on the chemical structure of the polymer was studied by using FTIR-spectroscopy with attenuated total reflection (ATR) and changes in the crystalline structure were determined by differential scan calorimetry DSC and X-ray diffraction technique. The lignin peroxidase (LiP) activity was followed by UV-spectrophotometry. We concluded that after 20 days of fermentation the copolymer has lost 50 percent of the initial crystalline structure.