Focused X-ray Beam Research Articles

Conformal Coating of Orthopedic Plates with X-ray Scintillators and pH Indicators for X-ray Excited Luminescence Chemical Imaging through Tissue.

We describe a pH-indicating material that can be directly implanted or coated on orthopedic implant surfaces to provide high-spatial-resolution pH mapping through tissue by X-ray excited luminescence chemical imaging (XELCI). This is especially useful for detecting local pH changes during treatment of implant-associated infections. The material has two layers: an X-ray scintillator layer with Gd2O2S:Eu in epoxy, which emits 620 and 700 nm light when irradiated with X-rays, and a pH indicator dye layer, which absorbs some of the 620 nm light in a pH-dependent fashion. To acquire each pixel in the image, a focused X-ray beam irradiates a small region of scintillators and the ratio of 620 to 700 nm light is acquired through the tissue. Scanning the X-ray beam across the implant surface generates high-spatial-resolution chemical measurements. Two associated challenges are (1) to make robust sensors that can be implanted in tissue to measure local chemical concentrations specifically for metal orthopedic implants and (2) to conformally coat the implant surface with scintillators and pH indicator dyes in order to make measurements over a large area. Previously, we have physically pressed or glued a pH-sensitive hydrogel sensor onto the surface of an implant, but this is impractical for imaging over large irregular device areas such as an orthopedic plate with holes and edges. Herein, we describe a chemically sensitive and biocompatible XELCI sensor material that can conformally coat the implant surface. A two-part commercial-grade epoxy resin was mixed with Gd2O2S:Eu and adhered to the titanium surface. Sugar and salt particles were added to the surface of the epoxy as it cured to create a roughened surface and increase the surface area. On this roughened surface, a secondary layer of diacrylated polyethylene glycol (PEG) hydrogel, containing a pH sensitive dye, was polymerized. This combination of epoxy-PEG layers was found to adhere well to the metal implant unlike other previously tested polymer surfaces, which delaminated when exposed to water or humidity. The focused X-ray beam enabled 0.5 mm spatial resolution through 1 cm-thick tissue. The pH sensor-coated orthopedic plate was imaged with XELCI, through tissue, with different pH levels to acquire a calibration curve. The plates were also imaged through tissue, with a low pH region on one section due to growth of a Staphylococcus aureus biofilm. A pH sensor-coated stainless-steel rod with two distinct pH regions was inserted in a rabbit tibia specimen, and the pH was imaged through both bone and soft tissue. These studies demonstrate the use of pH sensor-coated orthopedic plates and rods for mapping the local pH through tissue during biofilm formation by XELCI.

Correction of the X-ray wavefront from compound refractive lenses using 3D printed refractive structures.

A refractive phase corrector optics is proposed for the compensation of fabrication error of X-ray optical elements. Here, at-wavelength wavefront measurements of the focused X-ray beam by knife-edge imaging technique, the design of a three-dimensional corrector plate, its fabrication by 3D printing, and use of a corrector to compensate for X-ray lens figure errors are presented. A rotationally invariant corrector was manufactured in the polymer IP-STM using additive manufacturing based on the two-photon polymerization technique. The fabricated corrector was characterized at the B16 Test beamline, Diamond Light Source, UK, showing a reduction in r.m.s. wavefront error of a Be compound refractive Lens (CRL) by a factor of six. The r.m.s. wavefront error is a figure of merit for the wavefront quality but, for X-ray lenses, with significant X-ray absorption, a form of the r.m.s. error with weighting proportional to the transmitted X-ray intensity has been proposed. The knife-edge imaging wavefront-sensing technique was adapted to measure rotationally variant wavefront errors from two different sets of Be CRL consisting of 98 and 24 lenses. The optical aberrations were then quantified using a Zernike polynomial expansion of the 2D wavefront error. The compensation by a rotationally invariant corrector plate was partial as the Be CRL wavefront error distribution was found to vary with polar angle indicating the presence of non-spherical aberration terms. A wavefront correction plate with rotationally anisotropic thickness is proposed to compensate for anisotropy in order to achieve good focusing by CRLs at beamlines operating at diffraction-limited storage rings.

Complete Strain Mapping of Nanosheets of Tantalum Disulfide.

Quasi-two-dimensional (quasi-2D) materials hold promise for future electronics because of their unique band structures that result in electronic and mechanical properties sensitive to crystal strains in all three dimensions. Quantifying crystal strain is a prerequisite to correlating it with the performance of the device and calls for high resolution but spatially resolved rapid characterization methods. Here, we show that using fly-scan nano X-ray diffraction, we can accomplish a tensile strain sensitivity below 0.001% with a spatial resolution of better than 80 nm over a spatial extent of 100 μm on quasi-2D flakes of 1T-TaS2. Coherent diffraction patterns were collected from a ∼100 nm thick sheet of 1T-TaS2 by scanning a 12 keV focused X-ray beam across and rotating the sample. We demonstrate that the strain distribution around micron- and submicron-sized "bubbles" that are present in the sample may be reconstructed from these images. The experiments use state-of-the-art synchrotron instrumentation and will allow rapid and nonintrusive strain mapping of thin-film samples and electronic devices based on quasi-2D materials.

Focus characterization of an X-ray free-electron laser by intensity correlation measurement of X-ray fluorescence.

This paper proposes and demonstrates a simple method using the intensity correlation of X-ray fluorescence to evaluate the focused beam size of an X-ray free-electron laser (XFEL). This method was applied to the sub-micrometre focused XFEL beam at the SPring-8 Angstrom Compact Free Electron Laser, and the beam size evaluated using the proposed method was consistent with that measured using the knife-edge scan method. The proposed method is readily applicable to extremely small X-ray spots and can be applied for the precise diagnostics of sub-10 nm focused X-ray beams which have recently emerged.

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

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 4mm 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. 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 ~0.2mm 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 ±0.75mm displacement in the three orthogonal directions and ±5° vertical/horizontal rotation of the eyeball. The simulated CNV treatments by 60-kVp focused x-ray beams show highly conformal delivery of dose to the lesion plus margin (0.75mm) with sharp dose fall-offs and controllable spatial modulation patterns. The 90%-10% isodose penumbra is <0.5mm. With a prescription dose of 16Gy 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. 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.

Iterative X-ray spectroscopic ptychography.

Spectroscopic ptychography is a powerful technique to determine the chemical composition of a sample with high spatial resolution. In spectro-ptychography, a sample is rastered through a focused X-ray beam with varying photon energy so that a series of phaseless diffraction data are recorded. Each chemical component in the material under investigation has a characteristic absorption and phase contrast as a function of photon energy. Using a dictionary formed by the set of contrast functions of each energy for each chemical component, it is possible to obtain the chemical composition of the material from high-resolution multi-spectral images. This paper presents SPA (spectroscopic ptychography with alternating direction method of multipliers), a novel algorithm to iteratively solve the spectroscopic blind ptychography problem. First, a nonlinear spectro-ptychography model based on Poisson maximum likelihood is designed, and then the proposed method is constructed on the basis of fast iterative splitting operators. SPA can be used to retrieve spectral contrast when considering either a known or an incomplete (partially known) dictionary of reference spectra. By coupling the redundancy across different spectral measurements, the proposed algorithm can achieve higher reconstruction quality when compared with standard state-of-the-art two-step methods. It is demonstrated how SPA can recover accurate chemical maps from Poisson-noised measurements, and its enhanced robustness when reconstructing reduced-redundancy ptychography data using large scanning step sizes is shown.

Shaped X-ray beams by channeling in polycapillary optics

Polycapillary optics (polyCO) is an x-ray optical unit used in different instruments in a wide variety of scientific and industrial applications. The optics works utilising the phenomenon of x-ray total external reflection at radiation transmission through the optics micro-channels. The polyCO devices, according to their geometries, are capable to focus x-ray beam, manipulate divergent or quasi parallel beams. Their use may reduce both size and weight of the device resulting in low power compact x-ray instruments. However, matching polyCO parameters is crucial for developing portable, remote or in-line, industrial sensors and novel instruments for materials science, chemical-environmental and bio-medical applications.In this work we present the analyses of x-ray beam formed behind polyCO devices paying attention to the parameters such as the radiation flux, focal spot-size and divergence. X-ray techniques will be also discussed to outline state of the art of world-wide polyCO-based research.

Radiation damage of liquid electrolyte during focused X-ray beam photoelectron spectroscopy

Ambient pressure X-ray photoelectron spectroscopy (APXPS) has evolved into an effective tool to analyze the chemical states of interfaces relevant to realistic environments and operating conditions. Herein we employ a graphene-capped microvolume arrays sample platform for scanning photoelectron spectro-microscopy (SPEM) of electrified liquid-solid electrochemical interfaces. By using highly electron and X-ray transparent graphene membrane as a working electrode, we probed the electronic structure of a model electrochemical system under operando conditions within the first few nanometers of the electrode/liquid electrolyte interface. We report the conditions when highly focused X-ray irradiation affects the chemistry at the liquid–solid interface due to solvent radiolysis by primary radiation, photoelectrons as well as secondary electrons. We recorded radiolytic products by photoemission spectroscopy and characterized their impact on the chemical speciation at the electrified solid-liquid interface. Three different exposure regimes were tested to elucidate the onset and dependence of XPS radiolytic signatures of the dose rate. The observed effects highlight the need for careful consideration of radiolytic processes for artifact-free liquid phase XPS measurements and data interpretation.

Development of a scanning soft X-ray spectromicroscope to investigate local electronic structures on surfaces and interfaces of advanced materials under conditions ranging from low vacuum to helium atmosphere.

A scanning soft X-ray spectromicroscope was recently developed based mainly on the photon-in/photon-out measurement scheme for the investigation of local electronic structures on the surfaces and interfaces of advanced materials under conditions ranging from low vacuum to helium atmosphere. The apparatus was installed at the soft X-ray beamline (BL17SU) at SPring-8. The characteristic features of the apparatus are described in detail. The feasibility of this spectromicroscope was demonstrated using soft X-ray undulator radiation. Here, based on these results, element-specific two-dimensional mapping and micro-XAFS (X-ray absorption fine structure) measurements are reported, as well as the observation of magnetic domain structures from using a reference sample of permalloy micro-dot patterns fabricated on a silicon substrate, with modest spatial resolution (e.g. ∼500 nm). Then, the X-ray radiation dose for Nafion® near the fluorine K-edge is discussed as a typical example of material that is not radiation hardened against a focused X-ray beam, for near future experiments.

X-ray fluorescence microscopy: A method of measuring ion concentrations in the ear

This technical note describes synchrotron x-ray fluorescence microscopy (XFM) as a method for measuring the concentrations of different elements in cross-sections of the ear at extremely high resolution. This method could be of great importance for addressing many open questions in hearing research. XFM uses synchrotron radiation to evoke emissions from many biologically relevant elements in the tissue. The intensity and wavelength of the emitted radiation provide a fingerprint of the tissue composition that can be used to measure the concentration of the elements in the sampled location. Here, we focus on energies that target biologically-relevant elements of the periodic table between magnesium and zinc. Since a highly focused x-ray beam is used, the spot size is well below 1 μm and the samples can be scanned at a nanometer lateral resolution. This study shows that measurement of the concentrations of different elements is possible in a mid-modiolar cross-section of a mouse cochlea. Images are presented that indicate potassium and chloride “hot spots” in the spiral ligament and the spiral limbus, providing experimental evidence for the potassium recycling pathway and showing the cochlear structures involved. Scans of a section obtained from the incus, one of the middle ear ossicles, in a developing mouse have shown that zinc is not uniformly distributed This supports the hypothesis that zinc plays a special role in the process of ossification. Although limited by sophisticated sample preparation and sectioning, the method provides ample exciting opportunities, to understand the role of genetics and epigenetics on hearing mechanisms in ontogeny and phylogeny.

The Crystallinity of Apatite in Contact with Metamict Pyrochlore from the Silver Crater Mine, ON, Canada

The purpose of this work is to evaluate the long-term effects of radiation on the structure of naturally occurring apatite in the hope of assessing its potential for use as a solid nuclear waste form for actinide sequestration over geologically relevant timescales. When a crystal is exposed to radioactivity from unstable constituent atoms undergoing decay, the crystal’s structure may become damaged. Crystalline materials rendered partially or wholly amorphous in this way are deemed “partially metamict” or “metamict” respectively. Intimate proximity of a non-radioactive mineral to a radioactive one may also cause damage in the former, evident, for example, in pleochroic haloes surrounding zircon inclusions in micas. Radiation damage may be repaired through the process of annealing. Experimental evidence suggests that apatite may anneal during alpha particle bombardment (termed “self-annealing”), which, combined with a low solubility in aqueous fluids and propensity to incorporate actinide elements, makes this mineral a promising phase for nuclear waste storage. Apatite evaluated in this study occurs in a Grenville-aged crustal carbonatite at the Silver Crater Mine in direct contact with U-bearing pyrochlore (var. betafite)—a highly radioactive mineral. Stable isotope analyses of calcite from the carbonatite yield δ18O and δ13C consistent with other similar deposits in the Grenville Province. Although apatite and betafite imaged using cathodoluminescence (CL) show textures indicative of fracture-controlled alteration, Pb isotope analyses of betafite from the Silver Crater Mine reported in previous work are consistent with a model of long term Pb loss from diffusion, suggesting the alteration was not recent. Thus, it is interpreted that these minerals remained juxtaposed with no further metamorphic overprint for ≈1.0 Ga, and therefore provide an ideal opportunity to study the effects of natural, actinide-sourced radiation on the apatite structure over long timescales. Through broad and focused X-ray beam analyses and electron backscatter diffraction (EBSD) mapping, the pyrochlore is shown to be completely metamict—exhibiting no discernible diffraction associated with crystallinity. Meanwhile, apatite evaluated with these methods is confirmed to be highly crystalline with no detectable radiation damage. However, the depth of α-decay damage is not well-understood, with reported depths ranging from tens of microns to just a few nanometers. EBSD, a surface sensitive technique, was therefore used to evaluate the crystallinity of apatite surfaces which had been in direct contact with radioactive pyrochlore, and the entire volume of small apatite crystals whose cores may have received significant radiation doses. The EBSD results demonstrate that apatite remains crystalline, as derived from sharp and correctly-indexed Kikuchi patterns, even on surfaces in direct contact with a highly radioactive source for prolonged periods in natural systems.

High-resolution x-ray luminescence computed tomography.

High-resolution imaging modalities play a critical role for advancing biomedical sciences. Recently, x-ray luminescence computed tomography (XLCT) imaging was introduced as a hybrid molecular imaging modality that combines the high-spatial resolution of x-ray imaging and molecular sensitivity of optical imaging. The narrow x-ray beam based XLCT imaging has been demonstrated to achieve high spatial resolution, even at depth, with great molecular sensitivity. Using a focused x-ray beam as the excitation source, orders of magnitude of increased sensitivity has been verified compared with previous methods with a collimated x-ray beam. In this work, we demonstrate the high-spatial resolution capabilities of our focused x-ray beam based XLCT imaging system by scanning two sets of targets, differing in the target size, embedded inside of two tissue-mimicking cylindrical phantoms. Gd2O2S:Eu3+ targets of 200 µm and 150 µm diameters were created and embedded with the same edge-to-edge distances as their diameters respectively. We scanned and reconstructed a single transverse section and successfully demonstrated that a focused x-ray beam with an average dual-cone size of 125 µm could separate the targets in both phantoms with good shape and location accuracy. We have also improved the current XLCT imaging system to make it feasible for fast three-dimensional XLCT scanning.

Imaging of transient magnetization dynamics of Co/Pt multilayer dots with X-ray magnetic circular dichroism excited by microwaves

We investigated the magnetization dynamics of Co/Pt multilayer dots with diameters in the micron scale by X-ray magnetic circular dichroism (XMCD) with a focused beam with submicron dimensions. XMCD measurement with soft and hard X-rays revealed that the magnetic moments of Co and Pt strongly couple and precess with the same cone angle in ferromagnetic resonance conditions. The transient magnetization behavior of Co/Pt multilayer dots was investigated by pump–probe XMCD measurement with a scanning focused X-ray beam. A non-uniform magnetization distribution with concentric geometry including the phase of magnetization precession was visualized with excitation frequencies up to 3.05 GHz.

A direct solver for the phase retrieval problem in ptychographic imaging

Measurements achieved with ptychographic imaging are a special case of diffraction measurements. They are generated by illuminating small parts of a sample with, e.g., a focused X-ray beam. By shifting the sample, a set of far-field diffraction patterns of the whole sample is then obtained. From a mathematical point of view those measurements are the squared modulus of the windowed Fourier transform of the sample. Thus, we have a phase retrieval problem for local Fourier measurements. A direct solver for this problem was introduced by Iwen, Viswanathan and Wang in 2016 and improved by Iwen, Preskitt, Saab and Viswanathan in 2018. Motivated by the applied perspective of ptychographic imaging, we present a generalization of this method and compare the different versions in numerical experiments. The new method proposed herein turns out to be more stable, particularly in the case of missing data.

Alignment of sample position and rotation during in situ synchrotron X-ray micro-diffraction experiments using a Laue cross-correlation approach

Laue micro-diffraction has proven to be able to reveal material properties at the sub-grain scale for many polycrystalline materials and is now routinely available at several synchrotron facilities, providing an approach for nondestructive three-dimensional probing of the microstructures and mechanical states of materials. However, for in situ experiments, maintaining the positioning of the sample throughout the experiment, to achieve a good alignment of the characterized volumes, is a challenging issue. The aim of the present work is to address this problem by developing an approach based on digital image correlation of focused-beam Laue diffraction patterns. The method uses small changes in the diffraction signal as a focused X-ray beam is scanned over a surface region to allow corrections to be made for both sample lateral movement and rotation. The method is demonstrated using a tensile deformation experiment on an Al sample with 2.5 µm average grain size. The results demonstrate an accuracy of 0.5 µm for sample position registration and a precision in sample rotation of ∼0.01°. The proposed method is fast to implement and does not require the use of additional surface markers.

Noninvasively Imaging pH at the Surface of Implanted Orthopedic Devices with X-ray Excited Luminescence Chemical Imaging.

Implanted medical device-associated infections are a leading cause of fixation failure, and early diagnosis is the key to successful treatment. During infection, acidosis near the implant plays a role in antibiotic resistance and low pH is a potential infection indicator. Herein, we describe a pH sensor which attaches to the implants to noninvasively image local pH with high spatial resolution. The sensor has two layers: a scintillator layer which emits 620 and 700 nm light upon X-ray irradiation and a pH indicator layer containing bromocresol green dye that absorbs 620 nm luminescence in neutral/basic pH and passes 700 nm light at all pHs. We also developed a dedicated imaging system capable of scanning relatively large specimens through thick tissues. A focused X-ray beam irradiates one spot on the sensor, and the 620to 700 nm peak ratio is measured to determine the local pH; images are acquired by scanning the X-ray beam across the surface and measuring the pH point-by-point. The sensor was covered with varying thickness slices of chicken breast tissue (0-19 mm) to evaluate how the tissue affects the peak intensity and ratio. Thick tissues attenuated both 620 and 700 nm light, with more attenuation at 620 nm than 700 nm. Although this spectral distortion shifted the pH calibration curve, the effect could be corrected for using a scintillator film region with no pH indicator layer as a spectral reference. The sensor was attached to an orthopedic plate affixed to a human cadaveric tibia and imaged through tissue. This approach provides both high spatial resolution from focused X-ray excitation and surface chemical specificity from the indicator dye, providing a tool for imaging local pH through tissue.

X-ray reflecto-interferometer based on compound refractive lenses.

An X-ray amplitude-splitting interferometer based on compound refractive lenses, which operates in the reflection mode, is proposed and realized. The idea of a reflecto-interferometer is to use a very simplified experimental setup where a focused X-ray beam reflected from parallel flat surfaces creates an interference pattern in a wide angular range. The functional capabilities of the interferometer were experimentally tested at the European Synchrotron Radiation Facility (ESRF) ID06 beamline in the X-ray energy range from 10 keV to 15 keV. The main features of the proposed approach, high spatial and temporal resolution, were demonstrated experimentally. The reflections from free-standing Si3N4 membranes, gold and resist layers were studied. Experimentally recorded interferograms are in good agreement with our simulations. The main advantages and future possible applications of the reflecto-interferometer are discussed.

3D printed nozzles on a silicon fluidic chip.

Serial femtosecond crystallography is a new method for protein structure determination utilizing intense and destructive X-ray pulses generated by free-electron lasers. The approach requires the means to deliver hydrated protein crystals to a focused X-ray beam and replenish them at the repetition rate of the pulses. A liquid-jet sample delivery system where a gas dynamic virtual nozzle is printed directly on a silicon-glass microfluidic chip using a 2-photon-polymerization 3D printing process is implemented. This allows for rapid prototyping and high-precision production of nozzles to suit the characteristics of a particular sample and opens up the possibility for high-throughput and versatile sample delivery systems that can integrate microfluidic components for sample detection, characterisation, or control. With the hybrid system described here, stable liquid jets with diameters between 1.5 µm at liquid flow rate of 1.5 µl/min and more than 20 µm at liquid flow rate of 100 µl/min under atmospheric and vacuum conditions are generated. The combination of 2D lithography with direct 3D printing may streamline the integration of free-form-features and also facilitate scale-up production of such integrated microfluidic devices that may be useful in many other applications such as flow cytometry and optofluidics.

Focused x-ray luminescence computed tomography: experimental studies.

X-ray luminescence computed tomography (XLCT) is an emerging hybrid molecular imaging modality and has shown great promises in overcoming the strong optical scattering in deep tissues. Though the narrow x-ray beam based XLCT imaging has been demonstrated to obtain high spatial resolution at depth, it suffers from a relatively long measurement time, hindering its practical applications. Recently, we have designed a focused x-ray beam based XLCT imaging system and have successfully performed imaging in about 7.5 seconds per section for a mouse sized object. However, its high spatial resolution capacity has not been fully implemented yet. In this paper, with a superfine focused x-ray beam we design a focused-x-ray luminescence tomography (FXLT) system for spatial resolution up to 94 μm. First, we have described our design in details. Then, we estimate the performance of the designed FXLT imaging system. Lastly, we have found that the spatial resolution of FXLT can be further improved by reducing the scan step size, which has been demonstrated by numerical simulations.

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

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. 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. 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. 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.