High resolution imaging with focused kV x-rays for small animal radio-neuromodulation.

BACKGROUND: High precision radiotherapy with small irradiator size has potential in many treatment applications involving small shallow targets, with small animal radio-neuromodulation as an intriguing example. A focused kV technique based on novel usage of polycapillary x-ray lenses can focus x-ray beams to <0.2 mm in diameter, which is ideal for such uses. PURPOSE: Such an application also requires high resolution CT images for treatment planning and setup. In this work, we demonstrate the feasibility of using a virtual focal spot generated with an x-ray lens to perform high-resolution CBCT acquisition. METHOD: The experiment with x-ray lens was set up on an x-ray tabletop system to generate a virtual focal spot. The flood field images with and without the x-ray lens were first compared. A pinhole image was acquired for the virtual focal spot and compared with the one acquired with the conventional focal spot without the lens. The planar imaging resolution with and without the lens were evaluated using a line pair resolution phantom. The spatial resolution of the two settings were estimated by reconstructing a 0.15-mm wire phantom and comparing its full width half maximum (FWHM). A CBCT scan of a rodent head was also acquired to further demonstrate the improved resolution using the x-ray lens. RESULT: The proposed imaging setup with x-ray lens had a limited exposure area of 5 cm by 5 cm on the detector, which was suitable for guiding radio-neuromodulation to a small target in rodent brain. Compared to conventional imaging acquisition with a measured x-ray focal spot of 0.395 mm FWHM, the virtual focal spot size was measured at 0.175 mm. The reduction in focal spot size with lens leads to an almost doubled planar imaging resolution and a 26% enhancement in 3D spatial resolution. A realistic CBCT acquisition of a rodent head mimicked the imaging acquisition step for radio-neuromodulation and further showed the improved visualization for fine structures. CONCLUSION: This work demonstrated that the focused kV x-ray technique was capable of generating small focal spot size of <0.2 mm, which substantially improved x-ray imaging resolution for small animal imaging.

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.

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.

Prospective Cardiovascular Genetics Evaluation in Spontaneous Coronary Artery Dissection.

BACKGROUND: Previous studies describing genetics evaluation in spontaneous coronary artery dissection (SCAD) have been retrospective in nature or presented as single case reports. As part of a dedicated clinical program, we evaluated patients in cardiovascular genetics clinic to determine the role of genetically triggered vascular disease and genetic testing in SCAD. METHODS AND RESULTS: Patient data were entered prospectively into the Massachusetts General Hospital SCAD registry database from July 2013 to September 2017. Clinically indicated genetic testing was conducted based on patient imaging, family history, physical examination, and patient preference. Of the 107 patients enrolled in the registry, 73 underwent cardiovascular genetics evaluation at our center (average age, 45.3±9.4 years; 85.3% female), and genetic testing was performed for 44 patients. A family history of aneurysm or dissection was not a prevalent feature in the study population, and only 1 patient had a family history of SCAD. Six patients (8.2%) had identifiable genetically triggered vascular disease: 3 with vascular Ehlers-Danlos syndrome (COL3A1), 1 with Nail-patella syndrome (LMX1B), 1 with autosomal dominant polycystic kidney disease (PKD1), and 1 with Loeys-Dietz syndrome (SMAD3). None of these 6 had radiographic evidence of fibromuscular dysplasia. CONCLUSIONS: In this series, 8.2% of the SCAD patients evaluated had a molecularly identifiable disorder associated with vascular disease. The most common diagnosis was vascular Ehlers-Danlos syndrome. Patients with positive gene testing were significantly younger at the time of their first SCAD event. A low threshold for genetic testing should be considered in patients with SCAD.

Design for a coherent-scatter imaging system compatible with screening mammography.

A system using a wide-slot beam and simple antiscatter grids or slots has been designed to provide a localized map of tissue type that could be overlaid on the simultaneous conventional transmission image to provide an inexpensive, low dose adjunct to conventional screening mammography. Depth information is obtainable from the stereoscopic viewing angles. The system was demonstrated to produce observable contrast between adipose tissue and a phantom chosen to mimic carcinoma at an exposure comparable with screening mammography. Imaging data was collected over a range of system parameters to optimize contrast and to allow verification of simulation modeling.

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.