On the equivalence of the X-ray scattering retrieval with beam tracking and analyser-based imaging using a synchrotron source.

X-ray phase contrast imaging (XPCI) methods give access to contrast mechanisms that are based on the refractive properties of matter on top of the absorption coefficient in conventional x-ray imaging. Ultra small angle x-ray scattering (USAXS) is a phase contrast mechanism that arises due to multiple refraction events caused by physical features of a scale below the physical resolution of the used imaging system. USAXS contrast can therefore give insight into subresolution structural information, which is an ongoing research topic in the vast field of different XPCI techniques. In this study, we quantitatively compare the USAXS signal retrieved by the beam tracking XPCI technique with the gold standard of the analyzer based imaging XPCI technique using a synchrotron x-ray source. We find that, provided certain conditions are met, the two methods measure the same quantity.

The Minor's test in Frey syndrome treated with botulinum toxin: Methodology and efficacy.

In this paper, we aimed at methodologically presenting a video-case of Frey Syndrome occurred after parotidectomy, assessed by means of Minor's Test and treated with intradermic botulinum toxin A (BoNT-A) injection. Although largely described in the literature, a detailed explanation of both the procedures has not been previously elucidated. In a more original approach, we also highlighted the role of the Minor's test in identifying the most affected skin areas and new insight on the patient-tailored approach provided by multiple injections of botulinum toxin. Six months after the procedure, the patient's symptoms were resolved, and no evident signs of Frey syndrome were detectable through the Minor's test.

Optimization of a customized simultaneous algebraic reconstruction technique algorithm for phase-contrast breast computed tomography.

Objective.To introduce the optimization of a customized GPU-based simultaneous algebraic reconstruction technique (cSART) in the field of phase-contrast breast computed tomography (bCT). The presented algorithm features a 3D bilateral regularization filter that can be tuned to yield optimal performance for clinical image visualization and tissues segmentation.Approach.Acquisitions of a dedicated test object and a breast specimen were performed at Elettra, the Italian synchrotron radiation (SR) facility (Trieste, Italy) using a large area CdTe single-photon counting detector. Tomographic images were obtained at 5 mGy of mean glandular dose, with a 32 keV monochromatic x-ray beam in the free-space propagation mode. Three independent algorithms parameters were optimized by using contrast-to-noise ratio (CNR), spatial resolution, and noise texture metrics. The results obtained with the cSART algorithm were compared with conventional SART and filtered back projection (FBP) reconstructions. Image segmentation was performed both with gray scale-based and supervised machine-learning approaches.Main results.Compared to conventional FBP reconstructions, results indicate that the proposed algorithm can yield images with a higher CNR (by 35% or more), retaining a high spatial resolution while preserving their textural properties. Alternatively, at the cost of an increased image 'patchiness', the cSART can be tuned to achieve a high-quality tissue segmentation, suggesting the possibility of performing an accurate glandularity estimation potentially of use in the realization of realistic 3D breast models starting from low radiation dose images.Significance.The study indicates that dedicated iterative reconstruction techniques could provide significant advantages in phase-contrast bCT imaging. The proposed algorithm offers great flexibility in terms of image reconstruction optimization, either toward diagnostic evaluation or image segmentation.

X-ray Phase-Contrast Radiography and Tomography with a Multiaperture Analyzer.

We present a multiaperture analyzer setup for performing x-ray phase contrast imaging in planar and three-dimensional modalities. The method is based on strongly structuring the x-ray beam with an amplitude modulator, before it reaches the sample, and on a multiaperture analyzing element before detection. A multislice representation of the sample is used to establish a quantitative relation between projection images and the corresponding three-dimensional distributions, leading to successful tomographic reconstruction. Sample absorption, phase, and scattering are retrieved from the measurement of five intensity projections. The method is tested on custom-built phantoms with synchrotron radiation: sample absorption and phase can be reliably retrieved also in combination with strong scatterers, simultaneously attaining high sensitivity and dynamic range.

Towards breast tomography with synchrotron radiation at Elettra: first images.

The aim of the SYRMA-CT collaboration is to set-up the first clinical trial of phase-contrast breast CT with synchrotron radiation (SR). In order to combine high image quality and low delivered dose a number of innovative elements are merged: a CdTe single photon counting detector, state-of-the-art CT reconstruction and phase retrieval algorithms. To facilitate an accurate exam optimization, a Monte Carlo model was developed for dose calculation using GEANT4. In this study, high isotropic spatial resolution (120 µm)(3) CT scans of objects with dimensions and attenuation similar to a human breast were acquired, delivering mean glandular doses in the range of those delivered in clinical breast CT (5-25 mGy). Due to the spatial coherence of the SR beam and the long distance between sample and detector, the images contain, not only absorption, but also phase information from the samples. The application of a phase-retrieval procedure increases the contrast-to-noise ratio of the tomographic images, while the contrast remains almost constant. After applying the simultaneous algebraic reconstruction technique to low-dose phase-retrieved data sets (about 5 mGy) with a reduced number of projections, the spatial resolution was found to be equal to filtered back projection utilizing a four fold higher dose, while the contrast-to-noise ratio was reduced by 30%. These first results indicate the feasibility of clinical breast CT with SR.

Objective measurements of image quality in synchrotron radiation phase-contrast imaging versus digital mammography.

PURPOSE: Phase-contrast mammography with synchrotron radiation is an innovative X-ray imaging practice that improves the identification of breast lesions. Previous studies have proven the superiority of the mammography images taken in the phase-contrast modality using synchrotron radiation beams as compared with images taken in conventional mammography by subjective analyses. However, to our knowledge, no previous study has compared different acquisition systems in order to quantify this improvement by means of objective robust indicators. In this research, we intend to quantify the superiority of phase-contrast imaging by means of objective metrics of image quality. METHODS: Images from the American College of Radiology Mammographic Accreditation Phantom were obtained at hospitals, in two digital mammography equipment and at the Elettra synchrotron radiation facility (Trieste, Italy), using free space propagation phase-contrast modality. Regions of interest were selected to analyze image quality at the fibers (phase object) and masses (area object) simulated on the phantom by means of the signal-to-noise ratio, the figure of merit, the contrast and the edge visibility. RESULTS: The image contrast and edge visibility were significantly higher at the phase-contrast modality as compared with digital mammography equipment. The figure of merit using phase-contrast modality was higher for the fibers and comparable for the masses. CONCLUSION: The results showed an improvement of the contrast and edge visibility in phase-contrast images. These improvements may be important in the detection of small lesions and details.

Evaluation of microbubble contrast agents for dynamic imaging with x-ray phase contrast.

X-rays are commonly used as a means to image the inside of objects opaque to visible light, as their short wavelength allows penetration through matter and the formation of high spatial resolution images. This physical effect has found particular importance in medicine where x-ray based imaging is routinely used as a diagnostic tool. Increasingly, however, imaging modalities that provide functional as well as morphological information are required. In this study the potential to use x-ray phase based imaging as a functional modality through the use of microbubbles that can be targeted to specific biological processes is explored. We show that the concentration of a microbubble suspension can be monitored quantitatively whilst in flow using x-ray phase contrast imaging. This could provide the basis for a dynamic imaging technique that combines the tissue penetration, spatial resolution, and high contrast of x-ray phase based imaging with the functional information offered by targeted imaging modalities.

Theory and preliminary experimental verification of quantitative edge illumination x-ray phase contrast tomography.

X-ray phase contrast imaging (XPCi) methods are sensitive to phase in addition to attenuation effects and, therefore, can achieve improved image contrast for weakly attenuating materials, such as often encountered in biomedical applications. Several XPCi methods exist, most of which have already been implemented in computed tomographic (CT) modality, thus allowing volumetric imaging. The Edge Illumination (EI) XPCi method had, until now, not been implemented as a CT modality. This article provides indications that quantitative 3D maps of an object's phase and attenuation can be reconstructed from EI XPCi measurements. Moreover, a theory for the reconstruction of combined phase and attenuation maps is presented. Both reconstruction strategies find applications in tissue characterisation and the identification of faint, weakly attenuating details. Experimental results for wires of known materials and for a biological object validate the theory and confirm the superiority of the phase over conventional, attenuation-based image contrast.

Comparison of single distance phase retrieval algorithms by considering different object composition and the effect of statistical and structural noise.

Phase retrieval is a technique for extracting quantitative phase information from X-ray propagation-based phase-contrast tomography (PPCT). In this paper, the performance of different single distance phase retrieval algorithms will be investigated. The algorithms are herein called phase-attenuation duality Born Algorithm (PAD-BA), phase-attenuation duality Rytov Algorithm (PAD-RA), phase-attenuation duality Modified Bronnikov Algorithm (PAD-MBA), phase-attenuation duality Paganin algorithm (PAD-PA) and phase-attenuation duality Wu Algorithm (PAD-WA), respectively. They are all based on phase-attenuation duality property and on weak absorption of the sample and they employ only a single distance PPCT data. In this paper, they are investigated via simulated noise-free PPCT data considering the fulfillment of PAD property and weakly absorbing conditions, and with experimental PPCT data of a mixture sample containing absorbing and weakly absorbing materials, and of a polymer sample considering different degrees of statistical and structural noise. The simulation shows all algorithms can quantitatively reconstruct the 3D refractive index of a quasi-homogeneous weakly absorbing object from noise-free PPCT data. When the weakly absorbing condition is violated, the PAD-RA and PAD-PA/WA obtain better result than PAD-BA and PAD-MBA that are shown in both simulation and mixture sample results. When considering the statistical noise, the contrast-to-noise ratio values decreases as the photon number is reduced. The structural noise study shows that the result is progressively corrupted by ring-like artifacts with the increase of structural noise (i.e. phantom thickness). The PAD-RA and PAD-PA/WA gain better density resolution than the PAD-BA and PAD-MBA in both statistical and structural noise study.

Image quality evaluation of breast tomosynthesis with synchrotron radiation.

PURPOSE: This study investigates the image quality of tomosynthesis slices obtained from several acquisition sets with synchrotron radiation using a breast phantom incorporating details that mimic various breast lesions, in a heterogeneous background. METHODS: A complex Breast phantom (MAMMAX) with a heterogeneous background and thickness that corresponds to 4.5 cm compressed breast with an average composition of 50% adipose and 50% glandular tissue was assembled using two commercial phantoms. Projection images using acquisition arcs of 24°, 32°, 40°, 48°, and 56° at incident energy of 17 keV were obtained from the phantom with the synchrotron radiation for medical physics beamline at ELETTRA Synchrotron Light Laboratory. The total mean glandular dose was set equal to 2.5 mGy. Tomograms were reconstructed with simple multiple projection algorithm (MPA) and filtered MPA. In the latter case, a median filter, a sinc filter, and a combination of those two filters were applied on the experimental data prior to MPA reconstruction. Visual inspection, contrast to noise ratio, contrast, and artifact spread function were the figures of merit used in the evaluation of the visualisation and detection of low- and high-contrast breast features, as a function of the reconstruction algorithm and acquisition arc. To study the benefits of using monochromatic beams, single projection images at incident energies ranging from 14 to 27 keV were acquired with the same phantom and weighted to synthesize polychromatic images at a typical incident x-ray spectrum with W target. RESULTS: Filters were optimised to reconstruct features with different attenuation characteristics and dimensions. In the case of 6 mm low-contrast details, improved visual appearance as well as higher contrast to noise ratio and contrast values were observed for the two filtered MPA algorithms that exploit the sinc filter. These features are better visualized at extended arc length, as the acquisition arc of 56° with 15 projection images demonstrates the highest image reconstruction quality. For microcalcifications, filtered MPA implemented with a combination of median and sinc filters indicates better feature appearance due to efficient suppression of background tissue. The image quality of these features is less sensitive to the acquisition arc. Calcifications with size ranging from 170 to 500 µm, like the ones presently studied, are well identified and visualized for all arcs used. The comparison of single projection images obtained under different beam conditions showed that the use of monochromatic beam can produce an image with higher contrast and contrast to noise ratio compared to an image corresponding to a polychromatic beam even when the latter is acquired with double incident exposure. CONCLUSIONS: Filter optimization in respect to the type of feature characteristics is important before the reconstruction. The MPA combined with median and sinc filters results in improved reconstruction of microcalcifications and low-contrast features. The latter are better visualized at extended arc length, while microcalcifications are less sensitive to this acquisition parameter. Use of monochromatic beams may result in tomographic images with higher contrast acquired at lower incident exposures.

LGI1 microdeletion in autosomal dominant lateral temporal epilepsy.

OBJECTIVES: To characterize clinically and genetically a family with autosomal dominant lateral temporal epilepsy (ADLTE) negative to LGI1 exon sequencing test. METHODS: All participants were personally interviewed and underwent neurologic examination. Most affected subjects underwent EEG and neuroradiologic examinations (CT/MRI). Available family members were genotyped with the HumanOmni1-Quad v1.0 single nucleotide polymorphism (SNP) array beadchip and copy number variations (CNVs) were analyzed in each subject. LGI1 gene dosage was performed by real-time quantitative PCR (qPCR). RESULTS: The family had 8 affected members (2 deceased) over 3 generations. All of them showed GTC seizures, with focal onset in 6 and unknown onset in 2. Four patients had focal seizures with auditory features. EEG showed only minor sharp abnormalities in 3 patients and MRI was unremarkable in all the patients examined. Three family members presented major depression and anxiety symptoms. Routine LGI1 exon sequencing revealed no point mutation. High-density SNP array CNV analysis identified a genomic microdeletion about 81 kb in size encompassing the first 4 exons of LGI1 in all available affected members and in 2 nonaffected carriers, which was confirmed by qPCR analysis. CONCLUSIONS: This is the first microdeletion affecting LGI1 identified in ADLTE. Families with ADLTE in which no point mutations are revealed by direct exon sequencing should be screened for possible genomic deletion mutations by CNV analysis or other appropriate methods. Overall, CNV analysis of multiplex families may be useful for identifying microdeletions in novel disease genes.

Phase retrieval in quantitative x-ray microtomography with a single sample-to-detector distance.

Phase retrieval extracts quantitative phase information from x-ray propagation-based phase-contrast images. Notwithstanding inherent approximations, phase retrieval using a single sample-to-detector distance (SDD) is very attractive, because it imposes no setup complications or additional radiation dose compared to absorption-based imaging. Considering the phase-attenuation duality (ε=δ/ß, where ε is constant), a simple absorption correction factor is proposed for the modified Bronnikov algorithm in x-ray propagation-based phase-contrast computed tomography (PPCT). Moreover, a practical method for calculating the optimal ε value is proposed, which requires no prior knowledge of the sample. Tests performed on simulation and experimental data successfully distinguished different materials in a quasihomogeneous and weakly absorbing sample from a single SDD-PPCT data point.

Familial temporal lobe epilepsy with psychic auras associated with a novel LGI1 mutation.

BACKGROUND: Autosomal dominant lateral temporal epilepsy (ADLTE) is characterized by focal seizures with auditory features or aphasia. Mutations in the LGI1 gene have been reported in up to 50% of ADLTE pedigrees. We report a family with temporal lobe epilepsy characterized by psychic symptoms associated with a novel LGI1 mutation. METHODS: All participants were personally interviewed and underwent neurologic examination and video-EEG recordings. LGI1 exons were sequenced by standard methods. Mutant cDNA was transfected into human embryonic kidney 293 cells; both cell lysates and media were analyzed by Western blot. In silico modeling of the Lgi1 protein EPTP domain was carried out using the structure of WD repeat protein and manually refined. RESULTS: Three affected family members were ascertained, 2 of whom had temporal epilepsy with psychic symptoms (déjà vu, fear) but no auditory or aphasic phenomena, while the third had complex partial seizures without any aura. In all patients, we found a novel LGI1 mutation, Arg407Cys, which did not hamper protein secretion in vitro. Mapping of the mutation on a 3-dimensional protein model showed that this mutation does not induce large structural rearrangements but could destabilize interactions of Lgi1 with target proteins. CONCLUSIONS: The Arg407Cys is the first mutation with no effect on Lgi1 protein secretion. The uncommon, isolated psychic symptoms associated with it suggests that ADLTE encompasses a wider range of auras of temporal origin than hitherto reported.

Measurement of the linear attenuation coefficients of breast tissues by synchrotron radiation computed tomography.

The measurement of the linear attenuation coefficients of breast tissues is of fundamental importance in the field of breast x-ray diagnostic imaging. Different groups have evaluated the linear attenuation coefficients of breast tissues by carrying out direct attenuation measurements in which the specimens were thin and selected as homogeneous as possible. Here, we use monochromatic and high-intensity synchrotron radiation computed tomography (SR CT) to evaluate the linear attenuation coefficients of surgical breast tissues in the energy range from 15 to 26.5 keV. X-ray detection is performed by a custom digital silicon micro-strip device, developed in the framework of the PICASSO INFN experiment. Twenty-three human surgical breast samples were selected for SR CT and histological study. Six of them underwent CT, both as fresh tissue and after formalin fixation, while the remaining 17 were imaged only as formalin-fixed tissues. Our results for fat and fibrous tissues are in good agreement with the published values. However, in contrast to the published data, our measurements show no significant differences between fibrous and tumor tissues. Moreover, our results for fresh and formalin-fixed tissues demonstrate a reduction of the linear attenuation coefficient for fibrous and tumor tissues after fixation.

Microbubbles as x-ray scattering contrast agents using analyzer-based imaging.

Conventional contrast agents utilized in diagnostic radiology are based on x-ray absorption properties; alternative physical principles capable of providing a contrast enhancement in radiographs have never been applied. This study exploits the possibility of using a novel type of contrast media based on x-ray scattering. The contrast agents consist of microbubble echo-enhancing agents, usually applied in ultrasound examinations, which are invisible with conventional x-ray absorption techniques. The experiment was carried out at the medical beamline of the synchrotron radiation laboratory ELETTRA in Trieste, Italy. A flat silicon analyzer crystal typically used for diffraction-enhanced imaging was utilized as a tool for detecting the scattering properties of the contrast agents. In analyzer-based imaging, it is possible to detect the scattering properties of the sample by shifting the analyzer crystal to selected positions of its reflectivity curve. In particular, when the sample consists of a large number of micro-particles an overall effect can be observed. Phantoms containing contrast agents based on microbubbles were imaged at different angular positions of the analyzer crystal. High visibility of the details was demonstrated, and a strong contrast enhancement was measured compared to normal x-ray absorption techniques.

Phase contrast imaging of breast tumours with synchrotron radiation.

Even though the potential of phase contrast (PC) imaging has been demonstrated in a number of biological tissue samples, the availability of free-space propagation phase contrast images of real breast tumours is still limited. The aim of this study was to obtain phase contrast images of two different pathological breast specimens containing tumours of differing morphological type at two synchrotron radiation (SR) facilities, and to assess any qualitative improvements in the evaluation and characterisation of the masses through the use of phase contrast imaging. A second aim was to assess the effects of parameters such as detector resolution, beam energy and sample-to-detector distance on image quality using the same breast specimens, as to date these effects have been modelled and discussed only for geometric phantoms. At each synchrotron radiation facility a range of images was acquired with different detectors and by varying the above parameters. Images of the same samples were also acquired with the absorption-based approach to allow a direct comparison and estimation of the advantages specifically ascribable to the PC technique.

Synchrotron-based in vivo tracking of implanted mammalian cells.

We have developed an X-ray imaging protocol that permits 3D visualisation of a small number of implanted cells within bulk tissue. The cells are marked using natural endocytosis of inert gold nano-particles. The resulting local increase in electron density allows high imaging contrast to be obtained from small clusters of these marked cells. Using this technique we have imaged C6 glioma cells within the brain of a model animal. The cells were marked by exposing them to colloidal gold incorporated in the growth media. Gold-loaded glioma cells were implanted into the brains of adult male Wistar rats. After tumours had been allowed to develop for up to 2 weeks, the animals were sacrificed and images of the intact cranium were acquired at the SYRMEP imaging station on the Elettra synchrotron in Italy. Computed tomography was performed using mixed absorption and phase contrast techniques at an X-ray energy of 24 keV. In the resulting volume datasets the tumour bulk is clearly visible and the infiltrating nature of the malignant growth is well demonstrated. Although the protocol was developed using this particular model of malignant brain tumour, it is believed that it will be possible to use it with other cell lines.

The mammography project at the SYRMEP beamline.

A clinical program for X-ray phase contrast (PhC) mammography with synchrotron radiation (SR) has been started in March 2006 at the SYRMEP beamline of Elettra, the SR facility in Trieste, Italy. The original beamline layout has been modified substantially and a clinical facility has been realized. In order to fulfill all security requirements, dedicated systems have been designed and implemented, following redundancy criteria and "fail safe" philosophy. Planar radiographic images are obtained by scanning simultaneously the patient and the detector through the stationary and laminar SR beam. In this first phase of the project a commercial screen-film system has been used as image receptor. Upon approval by the respective authorities, the mammography program is about half way to conclusion. Up to now about 50 patients have been examined. The patients are volunteers recruited by the radiologist after conventional examinations at the hospital resulted in an uncertain diagnosis. As an example one case of PhC SR mammography is shown and compared to conventional digital mammography. Preliminary analysis shows the high diagnostic quality of the PhC SR images that were acquired with equal or less delivered dose compared to the conventional ones.

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging.

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

The effects of the imaging system on the validity limits of the ray-optical approach to phase contrast imaging.

A theoretical analysis of the x-ray phase contrast imaging and its validation via synchrotron radiation imaging is here presented. Two different mathematical models have been followed: the simpler ray-optical approach and the more rigorous Fresnel-Kirchoff diffraction theory. Subsequently, the conditions upon which the x-ray optical approximation can be used to describe the image formation mechanism have been analyzed, taking into account also the effects due to the finite source size and detector resolution. It is possible to demonstrate that the ray-optics results can also be obtained by opportunely developing the diffraction formalism only with some restrictions on the spatial frequencies present in the final image, without any limitation on the maximum phase shift. The conditions allowing the use of the simplified ray-optical approach to describe the phase contrast images have been here defined and their validation has been proved by means of computer simulations and phantom experiments.