Radiation dose reduction and image enhancement in biological imaging through equally-sloped tomography

Electron tomography is currently the highest resolution imaging modality available to study the 3D structures of pleomorphic macromolecular assemblies, viruses, organelles and cells. Unfortunately, the resolution is currently limited to 3–5 nm by several factors including the dose tolerance of biological specimens and the inaccessibility of certain tilt angles. Here we report the first experimental demonstration of equally-sloped tomography (EST) to alleviate these problems. As a proof of principle, we applied EST to reconstructing frozen-hydrated keyhole limpet hemocyanin molecules from a tilt-series taken with constant slope increments. In comparison with weighted back-projection (WBP), the algebraic reconstruction technique (ART) and the simultaneous algebraic reconstruction technique (SART), EST reconstructions exhibited higher contrast, less peripheral noise, more easily detectable molecular boundaries and reduced missing wedge effects. More importantly, EST reconstructions including only two-thirds the original images appeared to have the same resolution as full WBP reconstructions, suggesting that EST can either reduce the dose required to reach a given resolution or allow higher resolutions to be achieved with a given dose. EST was also applied to reconstructing a frozen-hydrated bacterial cell from a tilt-series taken with constant angular increments. The results confirmed similar benefits when standard tilts are utilized

dose reduction and image enhancement in biological imaging through equally-sloped tomography [J

a b s t r a c t Electron tomography is currently the highest resolution imaging modality available to study the 3D structures of pleomorphic macromolecular assemblies, viruses, organelles and cells. Unfortunately, the resolution is currently limited to 3-5 nm by several factors including the dose tolerance of biological specimens and the inaccessibility of certain tilt angles. Here we report the first experimental demonstration of equally-sloped tomography (EST) to alleviate these problems. As a proof of principle, we applied EST to reconstructing frozen-hydrated keyhole limpet hemocyanin molecules from a tilt-series taken with constant slope increments. In comparison with weighted back-projection (WBP), the algebraic reconstruction technique (ART) and the simultaneous algebraic reconstruction technique (SART), EST reconstructions exhibited higher contrast, less peripheral noise, more easily detectable molecular boundaries and reduced missing wedge effects. More importantly, EST reconstructions including only twothirds the original images appeared to have the same resolution as full WBP reconstructions, suggesting that EST can either reduce the dose required to reach a given resolution or allow higher resolutions to be achieved with a given dose. EST was also applied to reconstructing a frozen-hydrated bacterial cell from a tilt-series taken with constant angular increments. The results confirmed similar benefits when standard tilts are utilized

Three-dimensional structure determination from a single view

The ability to determine the structure of matter in three dimensions has profoundly advanced our understanding of nature. Traditionally, the most widely used schemes for 3D structure determination of an object are implemented by acquiring multiple measurements over various sample orientations, as in the case of crystallography and tomography (1,2), or by scanning a series of thin sections through the sample, as in confocal microscopy (3). Here we present a 3D imaging modality, termed ankylography (derived from the Greek words ankylos meaning 'curved' and graphein meaning 'writing'), which enables complete 3D structure determination from a single exposure using a monochromatic incident beam. We demonstrate that when the diffraction pattern of a finite object is sampled at a sufficiently fine scale on the Ewald sphere, the 3D structure of the object is determined by the 2D spherical pattern. We confirm the theoretical analysis by performing 3D numerical reconstructions of a sodium silicate glass structure at 2 Angstrom resolution and a single poliovirus at 2 - 3 nm resolution from 2D spherical diffraction patterns alone. Using diffraction data from a soft X-ray laser, we demonstrate that ankylography is experimentally feasible by obtaining a 3D image of a test object from a single 2D diffraction pattern. This approach of obtaining complete 3D structure information from a single view is anticipated to find broad applications in the physical and life sciences. As X-ray free electron lasers (X-FEL) and other coherent X-ray sources are under rapid development worldwide, ankylography potentially opens a door to determining the 3D structure of a biological specimen in a single pulse and allowing for time-resolved 3D structure determination of disordered materials.Comment: 30 page

Tungsten filled 3D printed field shaping devices for electron beam radiation therapy.

PurposeElectron radiotherapy is a labor-intensive treatment option that is complicated by the need for field shaping blocks. These blocks are typically made from casting Cerrobend alloys containing lead and cadmium. This is a highly toxic process with limited precision. This work aims to provide streamlined and more precise electron radiotherapy by 3D using printing techniques.MethodsThe 3D printed electron cutout consists of plastic shells filled with 2 mm diameter tungsten ball bearings. Five clinical Cerrobend defined field were compared to the planned fields by measuring the light field edge when mounted in the electron applicator on a linear accelerator. The dose transmitted through the 3D printed and Cerrobend cutouts was measured using an IC profiler ion chamber array with 6 MeV and 16 MeV beams. Dose profiles from the treatment planning system were also compared to the measured dose profiles. Centering and full width half maximum (FWHM) metrics were taken directly from the profiler software.ResultsThe transmission of a 16MeV beam through a 12 mm thick layer of tungsten ball bearings agreed within 1% of a 15 mm thick Cerrobend block (measured with an ion chamber array). The radiation fields shaped by ball bearing filled 3D printed cutout were centered within 0.4 mm of the planned outline, whereas the Cerrobend cutout fields had shift errors of 1-3 mm, and shape errors of 0.5-2 mm. The average shift of Cerrobend cutouts was 2.3 mm compared to the planned fields (n = 5). Beam penumbra of the 3D printed cutouts was found to be equivalent to the 15 mm thick Cerrobend cutout. The beam profiles agreed within 1.2% across the whole 30 cm profile widths.ConclusionsThis study demonstrates that with a proper quality assurance procedure, 3D-printed cutouts can provide more accurate electron radiotherapy with reduced toxicity compared to traditional Cerrobend methods

A Bayesian approach to real-time 3D tumor localization via monoscopic x-ray imaging during treatment delivery

Purpose: Monoscopic x-ray imaging with on-board kV devices is an attractive approach for real-time image guidance in modern radiation therapy such as VMAT or IMRT, but it falls short in providing reliable information along the direction of imaging x-ray. By effectively taking consideration of projection data at prior times and/or angles through a Bayesian formalism, the authors develop an algorithm for real-time and full 3D tumor localization with a single x-ray imager during treatment delivery