Grating-free quantitative phase retrieval for x-ray phase-contrast imaging with conventional sources.

X-ray phase-contrast imaging can display subtle differences in low-density materials (e.g. soft tissues) more readily than conventional x-ray imaging. However, producing x-ray phase images requires significant spatial coherence of the beam which in turn requires highly specialized sources such as synchrotrons, small and low power microfocus sources, or complex procedures, such as multiple exposures with several carefully stepped precision gratings. To find appropriate approaches for producing x-ray phase-contrast imaging in a clinically meaningful way, we employed a grating-free method that utilized a low-cost, coarse wire mesh and simple processing. This method relaxes the spatial coherence constraint and allows quantitative phase retrieval for not only monochromatic but also polychromatic beams. We also combined the mesh-based system with polycapillary optics to significantly improve the accuracy of quantitative phase retrieval.

Phase and dark-field imaging with mesh-based structured illumination and polycapillary optics.

PURPOSE: X-ray phase and dark-field (DF) imaging have been shown to improve the diagnostic capabilities of X-ray systems. However, these methods have found limited clinical use due to the need for multiple precision gratings with limited field of view or requirements on X-ray coherence that may not be easily translated to clinical practice. This work aims to develop a practicable X-ray phase and DF imaging system that could be translated and practiced in the clinic. METHODS: This work employs a conventional source to create structured illumination with a simple wire mesh. A mesh-shifting algorithm is used to allow wider Fourier windowing to enhance resolution. Deconvolution of the source spot width and camera resolution improves accuracy. Polycapillary optics are employed to enhance coherence. The effects of incorporating optics with two different focal lengths are compared. Information apparent in enhanced absorption images, phase images, and DF images of fat embedded phantoms were compared and subjected to a limited receiver operator characteristic (ROC) study. The DF images of the moist and dry porous object (sponges) were compared. RESULTS: The mesh-based phase and DF imaging system constructs images with three different information types: scatter-free absorption images, differential phase images, and scatter magnitude/DF images, simultaneously from the same original image. The polycapillary optic enhances the coherence of the beam. The deblurring technique corrects the phase signal error due to geometrical blur and the limitation of the camera modulation transfer function (MTF) and removes image artifacts to improve the resolution in a single shot. The mesh-shifting method allows the use of a wider Fourier processing window, which gives even higher resolution, at the expense of an increased dose. The limited ROC study confirms the efficacy of the system over the conventional system. DF images of moist and dry porous object show the significance of the system in the imaging of lung infections. CONCLUSION: The mesh-based X-ray phase and DF imaging system is an inexpensive and easy setup in terms of alignment and data acquisition and can produce phase and DF images in a single shot with wide field of view. The system shows significant potential for use in diagnostic imaging in a clinical setting.

Dosimetry modeling of focused kV x-ray radiotherapy for wet age-related macular degeneration.

PURPOSE: Wet (neovascular) age-related macular degeneration (AMD) is the leading cause of blindness in the United States. The mainstay treatment requires monthly intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs, associated with multiple visits, high cost, and the risk of procedural injury and infection. Anti-VEGF drugs inhibit the formation of neovasculature but do not directly attack it. Radiotherapy can destroy neovasculature and potentially also inhibit wet-AMD associated inflammation and fibrosis not addressed by VEGF inhibitors. However, the current collimation-based radiotherapy device uses fixed 4 mm beams, which are prone to overtreat or undertreat the choroidal neovascularization (CNV) lesions because of their various sizes and shapes. This simulation study evaluates personalized conformal treatment with focused kV radiation using cutting-edge polycapillary x-ray optics. METHODS: Simulation of the polycapillary optics was achieved via Monte Carlo (MC)-based three-dimensional (3D) geometric ray tracing. Phase-space files modeling the focused photons were generated. The method was previously verified by phantom measurements. The ultrasmall ~0.2 mm beam focal spot perpendicular to the beam direction enables spatially fractionated grid therapy, which has been shown to preferentially damage abnormal neovascular blood vessels vs normal ones. Geant4-based MC simulations of scanning while rotating beam delivery were performed to conformally treat three clinical cases of large, medium, and small CNV lesions with regular and grid deliveries. Dose delivery uncertainties due to positioning errors were analyzed, including ±0.75 mm displacement in the three orthogonal directions and ±5° vertical/horizontal rotation of the eyeball. RESULTS: The simulated CNV treatments by 60-kVp focused x-ray beams show highly conformal delivery of dose to the lesion plus margin (0.75 mm) with sharp dose fall-offs and controllable spatial modulation patterns. The 90%-10% isodose penumbra is <0.5 mm. With a prescription dose of 16 Gy to the lesions, the critical structure doses are well below the tolerance. The average CNV dose varies within 10% (mostly within 4%) due to 0.75-mm linear displacements and 5-degree gaze angle rotation of the eyeball. CONCLUSION: Focused kV technique allows personalized treatment of CNV lesions and reduces unwanted radiation to adjacent healthy tissue. The simulated dose distribution is superior to currently available techniques.

Grandmothers as Change Agents: Developing a Culturally Appropriate Program to Improve Maternal and Child Nutrition in Sierra Leone.

BACKGROUND: Global recommendations on optimal maternal and child nutrition (MCN) practices are clear; however, there is limited literature 1) exploring how roles of family members influence those practices and on 2) designing programs accordingly. Researchers using a family-systems approach in the Global South find that grandmothers often play a vital role in MCN, yet most nutrition programs narrowly target mothers, thereby potentially limiting effectiveness. OBJECTIVES: This article reports on the results of qualitative research exploring the roles and influence of family members on MCN in southern Sierra Leone, the local MCN beliefs and practices, and how those findings informed the design of a culturally appropriate program. METHODS: Focus group discussions (FGDs) were conducted with mothers, fathers, and grandmothers in 9 communities in Bonthe District, Sierra Leone. We used participatory tools to explore family members' roles and local MCN beliefs and practices. Interviews were recorded by notetakers and coded and analyzed using a content analysis approach. RESULTS: A total of 88 mothers, 125 grandmothers, and 79 fathers participated in the FGDs. All groups indicated that 1) grandmothers are the culturally designated advisors and supervisors of women on MCN issues and 2) mothers are not autonomous decision makers and are greatly influenced by grandmothers. The research identified both beneficial MCN practices and gaps between optimal and existing MCN practices-particularly related to maternal diet during pregnancy and exclusive breastfeeding for 6 mo. Research findings were used to design a grandmother-inclusive program. CONCLUSIONS: Our research showed that mothers are embedded in a family system of caring and supervision where grandmothers have primary influence on MCN practices, clearly supporting the need for grandmothers to have a central role in community MCN programs. It also points to the need for increased use of a family-systems approach in designing public health nutrition programs.

An Innovative Grandmother-Inclusive Approach for Addressing Suboptimal Infant and Young Child Feeding Practices in Sierra Leone.

BACKGROUND: Suboptimal infant and young child feeding (IYCF) practices contribute to child undernutrition. Sierra Leone Demographic and Health Survey data show that IYCF practices remain poor despite modest improvements. Recent studies have identified the role of grandmothers as critical to child nutrition; however, in Sierra Leone to date, the potential for grandmothers to influence IYCF practices has not been investigated. OBJECTIVES: We examined how an innovative grandmother-inclusive approach (GMIA) can be used to address suboptimal IYCF practices. METHODS: Using a quasi-experimental design, we compared IYCF beliefs and practices between GMIA intervention communities (receiving monthly dialogue sessions on nutrition, quarterly community praise sessions, and intergenerational forums) and comparison communities (receiving standard nutrition education) in Bum chiefdom from 2013 and 2016. The quantitative endline survey targeted 101 pregnant women, 291 women with children aged <2 y, and 219 grandmothers. Statistical analyses utilized t tests and χ2 tests to examine differences between intervention and comparison communities at endline. Multivariate regression was used to determine the intervention's effect on IYCF outcomes of interest. RESULTS: Awareness of and participation in the GMIA was high among mothers and grandmothers in intervention communities. The percentage of infants and young children aged 0-23 mo (n = 291) exclusively breastfed during the first week of life was significantly higher in the intervention group (90.2% compared with 79.4%, P = 0.01). Among infants aged 6-23 mo (n = 219), the percentage achieving minimum dietary diversity and minimum acceptable diet was significantly higher in the intervention group (77.2% compared with 51.8%, P < 0.001; and 53.8% compared with 22.6%, P < 0.001, respectively). Differences in percentages achieving minimum meal frequency (MMF) were only significant for infants aged 9-23 mo, with the intervention group achieving a higher MMF (54.6% compared with 36.9%, P = 0.02). CONCLUSIONS: Results suggest that a GMIA that recognizes grandmothers' roles and strengthens their knowledge can contribute to improved IYCF practices.

Combined effects of intermittent hyperoxia and intermittent hypercapnic hypoxia on respiratory control in neonatal rats.

Chronic exposure to intermittent hyperoxia causes abnormal carotid body development and attenuates the hypoxic ventilatory response (HVR) in neonatal rats. We hypothesized that concurrent exposure to intermittent hypercapnic hypoxia would influence this plasticity. Newborn rats were exposed to alternating bouts of hypercapnic hypoxia (10% O2/6% CO2) and hyperoxia (30-40% O2) (5 cycles h-1, 24 h d-1) through 13-14 days of age; the experiment was run twice, once in a background of 21% O2 and once in a background of 30% O2 (i.e., "relative hyperoxia"). Hyperoxia had only small effects on carotid body development when combined with intermittent hypercapnic hypoxia: the carotid chemoafferent response to hypoxia was reduced, but this did not affect the HVR. In contrast, sustained exposure to 30% O2 reduced carotid chemoafferent activity and carotid body size which resulted in a blunted HVR. When given alone, chronic intermittent hypercapnic hypoxia increased carotid body size and reduced the hypercapnic ventilatory response but did not affect the HVR. Overall, it appears that intermittent hypercapnic hypoxia counteracted the effects of hyperoxia on the carotid body and prevented developmental plasticity of the HVR.

Monte Carlo dosimetry modeling of focused kV x-ray radiotherapy of eye diseases with potential nanoparticle dose enhancement.

PURPOSE: Eye plaque brachytherapy is the most common approach for intraocular cancer treatment. It is, however, invasive and subject to large setup uncertainty due to the surgical operation. We propose a novel-focused kV x-ray technique with potential nanoparticle (NP) enhancement and evaluate its application in treating choroidal melanoma and iris melanoma by Monte Carlo (MC) dosimetry modeling. METHODS: A polycapillary x-ray lens was used to focus 45 kVp x rays to achieve pinpoint accuracy of dose delivery to small tumors near critical structures. In addition to allowing for beam focusing, the use of kV x rays takes advantage of the strong photoelectric absorption of metallic NPs in that energy regime and hence strong radiosensitization. We constructed an MC simulation program that takes into account the x-ray optic modeling and used GEANT4 for dosimetric calculation. Extensive phantom measurements using a prototype-focused x-ray system were carried out. The MC simulation of simple geometry phantom irradiation was first compared to measurements to verify the x-ray optic lens modeling in conjunction with the Geant4 dosimetric calculation. To simulate tumor treatment, a geometric eye model and two tumor models were constructed. Dose distributions of the simulated treatments were then calculated. NP radiosensitization was also simulated for two concentrations of 2 nm gold NP (AuNP) uniformly distributed in the tumor. RESULTS: The MC-simulated full width at half maximum (FWHM) and central-axis depth dose of the focused kV x-ray beam match those measured on EBT3 films within ~10% around the depth of focus of the beam. Dose distributions of the simulated ocular tumor treatments show that focused x-ray beams can concentrate the high-dose region in or close to the tumor plus margin. For the simulated posterior choroidal tumor treatment, with sufficient tumor coverage, the doses to the optic disc and fovea are substantially reduced with focused x-ray therapy compared to eye plaque treatment (3.8 vs 39.8 Gy and 11.1 vs 53.8 Gy, respectively). The eye plaque treatment was calculated using an Eye Physics plaque with I-125 seeds under TG43 assumption. For the energy spectrum used in this study, the average simulated dose enhancement ratios (DERs) are roughly 2.1 and 1.1 for 1.0% and 0.1% AuNP mass concentration in the tumor, respectively. CONCLUSION: Compared to eye plaque brachytherapy, the proposed focused kV x-ray technique is noninvasive and shows great advantage in sparing healthy critical organs without sacrificing the tumor control. The NP radiation dose enhancement is considerable at our proposed kV range even with a low NP concentration in the tumor, providing better critical structure protection and more flexibility for treatment planning.

Coherent scatter imaging Monte Carlo simulation.

Conventional mammography can suffer from poor contrast between healthy and cancerous tissues due to the small difference in attenuation properties. Coherent scatter slot scan imaging is an imaging technique which provides additional information and is compatible with conventional mammography. A Monte Carlo simulation of coherent scatter slot scan imaging was performed to assess its performance and provide system optimization. Coherent scatter could be exploited using a system similar to conventional slot scan mammography system with antiscatter grids tilted at the characteristic angle of cancerous tissues. System optimization was performed across several parameters, including source voltage, tilt angle, grid distances, grid ratio, and shielding geometry. The simulated carcinomas were detectable for tumors as small as 5 mm in diameter, so coherent scatter analysis using a wide-slot setup could be promising as an enhancement for screening mammography. Employing coherent scatter information simultaneously with conventional mammography could yield a conventional high spatial resolution image with additional coherent scatter information.