T staging esophageal tumors with x rays.

With histopathology results typically taking several days, the ability to stage tumors during interventions could provide a step change in various cancer interventions. X-ray technology has advanced significantly in recent years with the introduction of phase-based imaging methods. These have been adapted for use in standard labs rather than specialized facilities such as synchrotrons, and approaches that enable fast 3D scans with conventional x-ray sources have been developed. This opens the possibility to produce 3D images with enhanced soft tissue contrast at a level of detail comparable to histopathology, in times sufficiently short to be compatible with use during surgical interventions. In this paper we discuss the application of one such approach to human esophagi obtained from esophagectomy interventions. We demonstrate that the image quality is sufficiently high to enable tumor T staging based on the x-ray datasets alone. Alongside detection of involved margins with potentially life-saving implications, staging tumors intra-operatively has the potential to change patient pathways, facilitating optimization of therapeutic interventions during the procedure itself. Besides a prospective intra-operative use, the availability of high-quality 3D images of entire esophageal tumors can support histopathological characterization, from enabling "right slice first time" approaches to understanding the histopathology in the full 3D context of the surrounding tumor environment.

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 effect of a variable focal spot size on the contrast channels retrieved in edge-illumination X-ray phase contrast imaging.

Multi-modal X-ray imaging allows the extraction of phase and dark-field (or "Ultra-small Angle Scatter") images alongside conventional attenuation ones. Recently, scan-based systems using conventional sources that can simultaneously output the above three images on relatively large-size objects have been developed by various groups. One limitation is the need for some degree of spatial coherence, achieved either through the use of microfocal sources, or by placing an absorption grating in front of an extended source. Both these solutions limit the amount of flux available for imaging, with the latter also leading to a more complex setup with additional alignment requirements. Edge-illumination partly overcomes this as it was proven to work with focal spots of up to 100 micron. While high-flux, 100 micron focal spot sources do exist, their comparatively large footprint and high cost can be obstacles to widespread translation. A simple solution consists in placing a single slit in front of a large focal spot source. We used a tunable slit to study the system performance at various effective focal spot sizes, by extracting transmission, phase and dark-field images of the same specimens for a range of slit widths. We show that consistent, repeatable results are obtained for varying X-ray statistics and effective focal spot sizes. As the slit width is increased, the expected reduction in the raw differential phase peaks is observed, compensated for in the retrieval process by a broadened sensitivity function. This leads to the same values being correctly retrieved, but with a slightly larger error bar i.e. a reduction in phase sensitivity. Concurrently, a slight increase in the dark-field signal is also observed.

On the influence of lipid-induced optical anisotropy for the bioimaging of exo- or endocytosis with interference microscopic imaging.

Some implementations of interference microscopy imaging use digital holographic measurements of complex scattered fields to reconstruct three-dimensional refractive index maps of weakly scattering, semi-transparent objects, frequently encountered in biological investigations. Reconstruction occurs through application of the object scattering potential which assumes an isotropic refractive index throughout the object. Here, we demonstrate that this assumption can in some circumstances be invalid for biological imaging due to the presence of lipid-induced optical anisotropy. We show that the nanoscale organization of lipids in the observation of cellular endocytosis with polarized light induces a significant change in far-field scattering. We obtain this result by presenting a general solution to Maxwell's equations describing light scattering of core-shell particles near an isotropic substrate covered with an anisotropic thin film. This solution is based on an extension of the Bobbert-Vlieger solution for particle scattering near a substrate delivering an exact solution to the scattering problem in the near field as well as far field. By applying this solution to study light scattering by a lipid vesicle near a lipid bilayer, whereby the lipids are represented through a biaxial optical model, we conclude through ellipsometry concepts that effective amounts of lipid-induced optical anisotropy significantly alter far-field optical scattering in respect to an equivalent optical model that neglects the presence of optical anisotropy.

Polarization-multiplexed encoding at nanometer scales.

Optical data storage was developed using binary encoding primarily due to signal to noise ratio considerations. We report on a multiplexing method that allows a seven fold storage increase, per storage layer, per side, and propose one that can yield theoretically a 20+ fold increase. Multiplexing is achieved by encoding information in polarization via appropriately oriented nanostructures that emit strongly polarized light when excited by unpolarized light. The storage increase is possible due to the significantly reduced crosstalk that results form using unpolarized light.

Confocal polarization imaging in high-numerical-aperture space.

In this work we describe theoretical and experimental physical aspects of high-resolution imaging polarimetry and its application to polarization-multiplexed encoding. We theoretically demonstrate that it is possible to resolve the orientation of two fixed dipole-like emitters placed significantly below the resolution limit if their emission is uncorrelated. Furthermore, we experimentally demonstrate this phenomenon by illuminating closely spaced asymmetric nanopits with unpolarized light and subsequently determining their individual orientation and position from the measured spatial distributions of the azimuth angle of the polarization and degree of polarization, respectively. Reduction of the optical resolution of the imaging system is also shown to only weakly affect resolution obtainable via polarization measurements.

Low-dose phase contrast tomography with conventional x-ray sources.

PURPOSE: The edge illumination (EI) x-ray phase contrast imaging (XPCi) method has been recently further developed to perform tomographic and, thus, volumetric imaging. In this paper, the first tomographic EI XPCi images acquired with a conventional x-ray source at dose levels below that used for preclinical small animal imaging are presented. METHODS: Two test objects, a biological sample and a custom-built phantom, were imaged with a laboratory-based EI XPCi setup in tomography mode. Tomographic maps that show the phase shift and attenuating properties of the object were reconstructed, and analyzed in terms of signal-to-noise ratio and quantitative accuracy. Dose measurements using thermoluminescence devices were performed. RESULTS: The obtained images demonstrate that phase based imaging methods can provide superior results compared to attenuation based modalities for weakly attenuating samples also in 3D. Moreover, and, most importantly, they demonstrate the feasibility of low-dose imaging. In addition, the experimental results can be considered quantitative within the constraints imposed by polychromaticity. CONCLUSIONS: The results, together with the method's dose efficiency and compatibility with conventional x-ray sources, indicate that tomographic EI XPCi can become an important tool for the routine imaging of biomedical samples.

The heat-shock response co-inducer arimoclomol protects against retinal degeneration in rhodopsin retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of inherited diseases that cause blindness due to the progressive death of rod and cone photoreceptors in the retina. There are currently no effective treatments for RP. Inherited mutations in rhodopsin, the light-sensing protein of rod photoreceptor cells, are the most common cause of autosomal-dominant RP. The majority of mutations in rhodopsin, including the common P23H substitution, lead to protein misfolding, which is a feature in many neurodegenerative disorders. Previous studies have shown that upregulating molecular chaperone expression can delay disease progression in models of neurodegeneration. Here, we have explored the potential of the heat-shock protein co-inducer arimoclomol to ameliorate rhodopsin RP. In a cell model of P23H rod opsin RP, arimoclomol reduced P23H rod opsin aggregation and improved viability of mutant rhodopsin-expressing cells. In P23H rhodopsin transgenic rat models, pharmacological potentiation of the stress response with arimoclomol improved electroretinogram responses and prolonged photoreceptor survival, as assessed by measuring outer nuclear layer thickness in the retina. Furthermore, treated animal retinae showed improved photoreceptor outer segment structure and reduced rhodopsin aggregation compared with vehicle-treated controls. The heat-shock response (HSR) was activated in P23H retinae, and this was enhanced with arimoclomol treatment. Furthermore, the unfolded protein response (UPR), which is induced in P23H transgenic rats, was also enhanced in the retinae of arimoclomol-treated animals, suggesting that arimoclomol can potentiate the UPR as well as the HSR. These data suggest that pharmacological enhancement of cellular stress responses may be a potential treatment for rhodopsin RP and that arimoclomol could benefit diseases where ER stress is a factor.

Medicine, material science and security: the versatility of the coded-aperture approach.

The principal limitation to the widespread deployment of X-ray phase imaging in a variety of applications is probably versatility. A versatile X-ray phase imaging system must be able to work with polychromatic and non-microfocus sources (for example, those currently used in medical and industrial applications), have physical dimensions sufficiently large to accommodate samples of interest, be insensitive to environmental disturbances (such as vibrations and temperature variations), require only simple system set-up and maintenance, and be able to perform quantitative imaging. The coded-aperture technique, based upon the edge illumination principle, satisfies each of these criteria. To date, we have applied the technique to mammography, materials science, small-animal imaging, non-destructive testing and security. In this paper, we outline the theory of coded-aperture phase imaging and show an example of how the technique may be applied to imaging samples with a practically important scale.

Evaluation of a new six degrees of freedom couch for radiation therapy.

PURPOSE: The aim of this work is to evaluate the geometric accuracy of a prerelease version of a new six degrees of freedom (6DoF) couch. Additionally, a quality assurance method for 6DoF couches is proposed. METHODS: The main principle of the performance tests was to request a known shift for the 6DoF couch and to compare this requested shift with the actually applied shift by independently measuring the applied shift using different methods (graph paper, laser, inclinometer, and imaging system). The performance of each of the six axes was tested separately as well as in combination with the other axes. Functional cases as well as realistic clinical cases were analyzed. The tests were performed without a couch load and with a couch load of up to 200 kg and shifts in the range between -4 and +4 cm for the translational axes and between -3° and +3° for the rotational axes were applied. The quality assurance method of the new 6DoF couch was performed using a simple cube phantom and the imaging system. RESULTS: The deviations (mean ± one standard deviation) accumulated over all performance tests between the requested shifts and the measurements of the applied shifts were -0.01 ± 0.02, 0.01 ± 0.02, and 0.01 ± 0.02 cm for the longitudinal, lateral, and vertical axes, respectively. The corresponding values for the three rotational axes couch rotation, pitch, and roll were 0.03° ± 0.06°, -0.04° ± 0.12°, and -0.01° ± 0.08°, respectively. There was no difference found between the tests with and without a couch load of up to 200 kg. CONCLUSIONS: The new 6DoF couch is able to apply requested shifts with high accuracy. It has the potential to be used for treatment techniques with the highest demands in patient setup accuracy such as those needed in stereotactic treatments. Shifts can be applied efficiently and automatically. Daily quality assurance of the 6DoF couch can be performed in an easy and efficient way. Long-term stability has to be evaluated in further tests.

Method for automatization of the alignment of a laboratory based x-ray phase contrast edge illumination system.

Here we present a general alignment algorithm for an edge illumination x-ray phase contrast imaging system, which is used with the laboratory systems developed at UCL. It has the flexibility to be used with all current mask designs, and could also be applied to future synchrotron based systems. The algorithm has proved to be robust experimentally, and can be used for the automatization of future commercial systems through automatic alignment and alignment correction.

Low-dose phase contrast mammography with conventional x-ray sources.

PURPOSE: To provide an x-ray phase contrast imaging (XPCI) method working with conventional sources that could be readily translated into clinical practice. XPCI shows potential in synchrotron studies but attempts at translating it for use with conventional sources are subject to limitations in terms of field of view, stability, exposure time, and possibly most importantly, delivered dose. METHODS: Following the adaptation of our "edge-illumination" XPCI technique for use with conventional x-ray sources through the use of x-ray masks, the authors have further modified the design of such masks to allow further reducing the dose delivered to the sample without affecting the phase sensitivity of the method. RESULTS: The authors have built a prototype based on the new mask design and used it to image ex vivo breast tissue samples containing malignant lesions. The authors compared images acquired with this prototype to those obtained with a conventional system. The authors demonstrate and quantify image improvements, especially in terms of microcalcification detection. On calcifications detected also by the conventional system, the authors measure contrast increases from five to nine fold; calcifications and other features were also detected which are completely invisible in the conventional image. Dose measurements confirmed that the above enhancements were achieved while delivering doses compatible with clinical practice. CONCLUSIONS: The authors obtained phase-related image enhancements in mammography by means of a system built with components available off-the-shelf that operates under exposure time and dose conditions compatible with clinical practice. This opens the way to a straightforward translation of phase enhanced imaging methods into clinical practice.

Diabetic fatty liver disease is associated with specific changes in blood-borne markers.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) can lead to cirrhosis and hepatocellular carcinoma and is strongly associated with obesity and insulin resistance. The aim of this study was to assess if plasma markers associated with NAFLD are increased in people with concomitant diabetes compared with those without. METHODS: A total of 68 participants were recruited from diabetes and liver clinics. Fatty liver disease was indicated by routine blood tests and ultrasonography. Forty-seven participants had type 2 diabetes; of them, 18 had no fatty liver disease as defined previously (DNoFLD) and 29 had fatty liver disease (DFLD); the remaining 21 had fatty liver disease but no diabetes (NonDFLD). Serum samples were analyzed for adiponectin (APN), alanine and aspartate aminotransferases and plasma for cholesterol, triglyceride, hyaluronic acid (HA), procollagen peptide III, alkaline phosphatase and fibrinogen. RESULTS: Hyaluronic acid and procollagen peptide III were significantly higher and adiponectin significantly lower in DFLD than NonDFLD and DNoFLD, the difference being particularly marked for hyaluronic acid and APN. There was no difference in these markers between NonDFLD and DNoFLD and no association between any plasma or serum marker and ultrasound grade of steatosis. CONCLUSION: We have identified markers of hepatic steatosis that appear to be specific for people with type 2 diabetes. A further longitudinal study is merited to assess the role of these markers in understanding the progression of hepatic steatosis and fibrosis in people with and without diabetes.

SU-E-J-39: Minimizing IGRT Imaging Exposures: KV Radiograph Vs. KV-CBCT Vs. MV Portal Images.

PURPOSE: To compare the IGRT doses from MV, kV and CBCT images. METHODS: kV imaging systems integrated into Varian Trilogy and TrueBeam accelerators were modeled using BEAMnrc/DOSXYZnrc Monte Carlo codes and the dose to calibration phantoms for a variety of kV beams(kVp, bow-tie filters, etc.) were calculated. The doses to the same phantoms and kV beams were then measured experimentally using calibrated ion-chambers.The "calibrated" Monte Carlo kV beams were used to calculate dose to CT images of patients. Organ doses were analyzed using DVHs. RESULTS: The doses to the prostate are 0.015 and 2.2cGy using AP kV and MV images; are 0.06 and 2.3cGy using lateral kV and MV images; and, are 1.7 cGy using CBCT images. For head and neck images, the doses to the eye are 0.08 and 0.001 cGy using AP and PA kV images; are 2.3 and 1.8cGy using AP and PA MV images; are 0.001 and 2.4cGy for lateral kV and MV images; and, are 0.2 cGy for CBCT images. For kV radiographs, organ doses can be further reduced, by over 30%, by using bow-tie filters. CBCT doses to the prostate are 1.6 and 0.9cGy for OBI and TrueBeam pelvis scans; a >40% dose reduction for the same image quality. For OBI CBCT head scans the doses to the eye and brain stem are 0.2 and 2.8cGy, respectively. CONCLUSIONS: Due to the low penetration of kV beams,selecting beam angles so that the sensitive organs are near the beam exit, and/or using bow-tie filters, can substantially reduce organ doses when using kV radiographs. For daily positioning of pediatric brain patient with a set of orthogonal kV images, a CBCT scan, or a set of orthogonal MV images, the doses to the eyes are 0.1, 0.2, and 4.7 cGy, respectively.

SU-E-I-15: Comparison of State-Of-The-Art Interpolation-Based Metal Artifact Reduction (MAR) Algorithms for Cone-Beam Computed Tomography (CBCT).

PURPOSE: To compare four metal-artifact-reduction (MAR) algorithms in their ability to correct the typical streaking artifacts that appear in cone- beam computed tomography (CBCT) images. METHODS: The goal was to compare the strengths and weaknesses of four MAR algorithms, Basic; Wei; Mazin and Meyer, using typical clinical situations where metal is present. Three clinical situations were evaluated: fiducial markers in the abdomen; hip implants and multiple dental fillings. The algorithms take original CBCT projections as input and produce a corrected image. The location of the metal is identified in the CBCT images and a forward projection identifies which pixels in the projections need to be replaced by interpolation of neighboring pixels. The three advanced algorithms extend the Basic technique with more sophisticated interpolation schemes. Wei and Meyer identify the high contrast structures using image segmentation in order to reduce their appearance in the projections before interpolation. Mazin corrects the original projections using a forward projection of the Basic correction. RESULTS: All the algorithms reduced the streak artifacts typical of metal structures. Nevertheless, depending upon the clinical task, the algorithms also added shading and streaks which reduced the overall visual impression. Images containing fiducial markers in the abdomen showed obvious improvements; images containing hip implants were improved but also showed distracting shading artifacts; and, images with multiple dental fillings all appeared visually worse than the uncorrected images. In almost all cases, Mazin outperformed the other approaches and introduced the fewest additional streaks and shading artifacts. CONCLUSIONS: This work indicates that the Mazin algorithm is best suited for clinical usage of MAR. Furthermore the algorithm is fairly simple and can be computational very efficient making it well suited for clinical use. Nevertheless, the overall improvement is highly dependent on the individual characteristics of the original image. For dental implants no correction is recommended.

Effects of signal diffusion on x-ray phase contrast images.

We discuss the problem of signal diffusion among neighbouring pixels in x-ray phase contrast imaging (XPCi) specifically for coded-aperture (CA) XPCi, but many of the discussed observations are directly transferable to other XPCi modalities. CA XPCi exploits the principle of pixel edge illumination by means of two CA masks. The first mask, placed in contact with the detector, creates insensitive regions between adjacent pixels; the second one, placed immediately before the sample, creates individual beams impinging on the boundaries between sensitive and insensitive regions on the detector, as created by the detector mask. In this way, edge illumination is achieved for all pixels of an area detector illuminated by a divergent and polychromatic beam generated by a conventional source. As the detector mask redefines the resolution properties of the detector, sample dithering can be used to effectively increase the system spatial resolution, without having to apply any post-processing procedure (e.g., deconvolution). This however creates artifacts in the form of secondary fringes (which have nothing to do with phase-related secondary fringes) if there is signal diffusion between adjacent pixels. In non-dithered images, signal diffusion between adjacent pixels causes a reduction in image contrast. This effect is investigated both theoretically and experimentally, and its direct implications on image quality are discussed. The interplay with the sample positioning with respect to the detector pixel matrix, which also has an effect on the obtained image contrast, is also discussed.

High prevalence of edin-C encoding RhoA-targeting toxin in clinical isolates of Staphylococcus aureus.

Staphylococcus aureus, a major causative agent of human infection, produces a large array of virulence factors, including various toxins. Among them, the host RhoA GTPase ADP-ribosylating EDIN toxins are considered as potential virulence factors. Using the polymerase chain reaction (PCR) assay, we analyzed the virulence profile of 256 S. aureus isolates from various clinical sites of infections. We developed specific primers to detect the three isoforms of edin-encoding genes. We found a prevalence of 14% (36 bacteria) of edin-encoding genes among these clinical isolates. Strikingly, we found that 90% of all edin-bearing S. aureus isolates carried the type-C allele. Both the spa types and the profile of virulence factors of these edin-positive isolates are highly variable. Notably, we show for the first time that edin-C-positive isolates were more frequently recovered from deep-seated infections than other types of infections. Our present work, thus, strongly suggests that the presence of edin-C is a risk factor of S. aureus dissemination in tissues and, thus, represents a predictive marker for a pejorative evolution of staphylococcal infections.

Pulmonary rehabilitation following lung transplantation.

Pulmonary rehabilitation (PR) following lung transplantation (LT) is regarded as part of best practice management; however, the optimal duration and composition of PR programs for LT patients is unknown. This study aimed to describe changes in functional outcomes of LT patients who participated in our standard outpatient post-LT PR program. A prospective, repeated measures design was used. Functional exercise capacity (6-minute walk distance [6MWD]), lung function (forced expiratory volume in 1 second [FEV(1)], forced vital capacity [FVC]) and quality of life (Short Form 34 [SF-36]) were assessed at 1, 2, and 3 months following LT. All subjects attended a 1-hour outpatient group exercise training class 3 days per week until 12 weeks post-LT and education sessions facilitated by the multidisciplinary team. Patients with postoperative complications (mechanical ventilation, major myopathy) were excluded. Data were analyzed using descriptive statistics and analysis of variance with repeated measures. Thirty-six subjects (50% men), 81% bilateral LT, mean age 46 +/- 14 years were included. Significant improvements were demonstrated in 6MWD (451 +/- 126 m to 543 +/- 107 m, P < .001), FEV(1) (71% +/- 18% to 81% +/- 4%, P < .0001), FVC (69% +/- 14% to 81% +/- 18%, P < .0001), and all SF36 domains (P < .05). Large improvements were seen in the first month of rehabilitation, with smaller but clinically significant improvements continuing in the second month. Further prospective, longitudinal studies are required to determine whether a longer period of pulmonary rehabilitation would result in additional improvements.

Rehabilitation and transition after lung transplantation in children.

We describe the key components of an outpatient pediatric recovery and rehabilitation program set up within the adult lung transplant service at the Alfred Hospital, Melbourne. Following discharge, pediatric lung transplant recipients and their families participated in an intensive 3-month outpatient rehabilitation program. Weekly sessions included education regarding transplant issues, physiotherapy, and occupational therapy sessions. The overall aim of the program was to comprehensively address physical rehabilitation and psychosocial and educational needs. Sessions tailored to meet the individual needs of the child were presented at an appropriate cognitive level. Education sessions for both the children and parents focused on medications, identification of infection and rejection, nutrition, physiotherapy/rehabilitation, occupational roles and stress management, donor issues, psychosocial readjustment, and transition issues. Physiotherapy included a progressive aerobic and strength training program, postural reeducation, and core stability. We incorporate Age-appropriate play activities: running, dancing, jumping, ball skills, and so on. Occupational therapy sessions addressed the primary roles of patient, students, and player. Transitions such as returning to school, friends, and the community were explored. Issues discussed included adjustment to new health status, strategies to manage side effects of medications, and altered body image issues. Weekly multidisciplinary team meetings were used to discuss and plan the rehabilitation progress. School liaison and visits occurred prior to school commencement with follow-up offered to review the ongoing transition process. Both patients and parents have reported a high level of satisfaction with the rehabilitation program. We plan to formally evaluate the program in the future.

Properties of high-numerical-aperture Mueller-matrix polarimeters.

To our knowledge there has been very little work done to establish the theoretical basis of high-NA Mueller matrix polarimetry. We consider how high-NA polarimetry differs from traditional wide-field polarimetry. We show that confocal polarimetry leads to an averaging of the sample Jones matrices, each of which is associated with one of the incident plane waves comprising the incident focused field and that a conventional polarimeter leads to an averaging of sample Mueller matrices. We conclude with an example.