X-ray-Sensitive Doped CaF2-Based MRI Contrast Agents for Local Radiation Dose Measurement.

Ionizing radiation has become widely used in medicine, with application in diagnostic techniques, such as computed tomography (CT) and radiation therapy (RT), where X-rays are used to diagnose and treat tumors. The X-rays used in CT and, in particular, in RT can have harmful side effects; hence, an accurate determination of the delivered radiation dose is of utmost importance to minimize any damage to healthy tissues. For this, medical specialists mostly rely on theoretical predictions of the delivered dose or external measurements of the dose. To extend the practical use of ionizing radiation-based medical techniques, such as magnetic resonance imaging (MRI)-guided RT, a more precise measurement of the internal radiation dose internally is required. In this work, a novel approach is presented to measure dose in liquids for potential future in vivo applications. The strategy relies on MRI contrast agents (CAs) that provide a dose-sensitive signal. The demonstrated materials are (citrate-capped) CaF2 nanoparticles (NPs) doped with Eu3+ or Fe2+/Fe3+ ions. Free electrons generated by ionizing radiation allow the reduction of Eu3+, which produces a very small contrast in MRI, to Eu2+, which induces a strong contrast. Oxidative species generated by high-energy X-rays can be measured indirectly using Fe2+ because it oxidizes to Fe3+, increasing the contrast in MRI. Notably, in the results, a strong increase in the proton relaxation rates is observed for the Eu3+-doped NPs at 40 kV. At 6 MV, a significant increase in proton relaxation rates is observed using CaF2 NPs doped with Fe2+/Fe3+ after irradiation. The presented concept shows great promise for use in the clinic to measure in vivo local ionizing radiation dose, as these CAs can be intravenously injected in a saline solution.

Material decomposition with a prototype photon-counting detector CT system: expanding a stoichiometric dual-energy CT method via energy bin optimization and K-edge imaging.

Objective.Computed tomography (CT) has advanced since its inception, with breakthroughs such as dual-energy CT (DECT), which extracts additional information by acquiring two sets of data at different energies. As high-flux photon-counting detectors (PCDs) become available, PCD-CT is also becoming a reality. PCD-CT can acquire multi-energy data sets in a single scan by spectrally binning the incident x-ray beam. With this, K-edge imaging becomes possible, allowing high atomic number (high-Z) contrast materials to be distinguished and quantified. In this study, we demonstrated that DECT methods can be converted to PCD-CT systems by extending the method of Bourqueet al(2014). We optimized the energy bins of the PCD for this purpose and expanded the capabilities by employing K-edge subtraction imaging to separate a high-atomic number contrast material.Approach.The method decomposes materials into their effective atomic number (Zeff) and electron density relative to water (ρe). The model was calibrated and evaluated using tissue-equivalent materials from the RMI Gammex electron density phantom with knownρevalues and elemental compositions. TheoreticalZeffvalues were found for the appropriate energy ranges using the elemental composition of the materials.Zeffvaried slightly with energy but was considered a systematic error. Anex vivobovine tissue sample was decomposed to evaluate the model further and was injected with gold chloride to demonstrate the separation of a K-edge contrast agent.Main results.The mean root mean squared percent errors on the extractedZeffandρefor PCD-CT were 0.76% and 0.72%, respectively and 1.77% and 1.98% for DECT. The tissue types in theex vivobovine tissue sample were also correctly identified after decomposition. Additionally, gold chloride was separated from theex vivotissue sample with K-edge imaging.Significance.PCD-CT offers the ability to employ DECT material decomposition methods, along with providing additional capabilities such as K-edge imaging.

Design and CT imaging of casper, an anthropomorphic breathing thorax phantom.

The goal of this work was to build an anthropomorphic thorax phantom capable of breathing motion with materials mimicking human tissues in x-ray imaging applications. The thorax phantom, named Casper, was composed of resin (body), foam (lungs), glow polyactic acid (bones) and natural polyactic acid (tumours placed in the lungs). X-ray attenuation properties of all materials prior to manufacturing were evaluated by means of photon-counting computed tomography (CT) imaging on a table-top system. Breathing motion was achieved by a scotch-yoke mechanism with diaphragm motion frequencies of 10-20 rpm and displacements of 1 to 2 cm. Casper was manufactured by means of 3D printing of moulds and ribs and assembled in a complex process. The final phantom was then scanned using a clinical CT scanner to evaluate material CT numbers and the extent of tumour motion. Casper CT numbers were close to human CT numbers for soft tissue (46 HU), ribs (125 HU), lungs (-840 HU) and tumours (-45 HU). For a 2 cm diaphragm displacement the largest tumour displacement was 0.7 cm. The five tumour volumes were accurately assessed in the static CT images with a mean absolute error of 4.3%. Tumour sizes were either underestimated for smaller tumours or overestimated for larger tumours in dynamic CT images due to motion blurring with a mean absolute difference from true volumes of 10.3%. More Casper information including a motion movie and manufacturing data can be downloaded from http://web.uvic.ca/~bazalova/Casper/.

Metal artifact correction in photon-counting detector computed tomography: metal trace replacement using high-energy data.

BACKGROUND: Metal artifacts have been an outstanding issue in computed tomography (CT) since its first uses in the clinic and continue to interfere. Metal artifact reduction (MAR) methods continue to be proposed and photon-counting detectors (PCDs) have recently been the subject of research toward this purpose. PCDs offer the ability to distinguish the energy of incident x-rays and sort them in a set number of energy bins. High-energy data captured using PCDs have been shown to reduce metal artifacts in reconstructions due to reduced beam hardening. PURPOSE: High-energy reconstructions using PCD-CT have their drawbacks, such as reduced image contrast and increased noise. Here, we demonstrate a MAR algorithm, trace replacement MAR (TRMAR), in which the data corrupted by metal artifacts in full energy spectrum projections are corrected using the high-energy data captured during the same scan. The resulting reconstructions offer similar MAR to that seen in high-energy reconstructions, but with improved image quality. METHODS: Experimental data were collected using a bench-top PCD-CT system with a cadmium zinc telluride PCD. Simulations were performed to determine the optimal high-energy threshold and to test TRMAR in simulations using the XCAT phantom and a biological sample. For experiments a 100-mm diameter cylindrical phantom containing vials of water, two screws, various densities of Ca(ClO4 )2 , and a spatial resolution phantom was imaged with and without the screws. The screws were segmented in the initial reconstruction and forward projected to identify them in the sinogram space in order to perform TRMAR. The resulting reconstructions were compared to the control and to reconstructions corrected using normalized metal artifact reduction (NMAR). Additionally, a beef short rib was imaged with and without metal to provide a more realistic phantom. RESULTS: XCAT simulations showed a reduction in the streak artifact from -978 HU in uncorrected images to -10 HU with TRMAR. The magnitude of the metal artifact in uncorrected images of the 100-mm phantom was -442 HU, compared to the desired -81 HU with no metal. TRMAR reduced the magnitude of the artifact to -142 HU, with NMAR reducing the magnitude to -96 HU. Relative image noise was reduced from 176% in the high-energy image to 56% using TRMAR. Density quantification was better with NMAR, with the Ca(ClO4 )2 vial affected most by metal artifacts showing 0.8% error compared to 2.1% with TRMAR. Small features were preserved to a greater extent with TRMAR, with the limiting spatial frequency at 20% of the MTF fully maintained at 1.31 lp/mm, while with NMAR it was reduced to 1.22 lp/mm. Images of the beef short rib showed better delineation of the shape of the metal using TRMAR. CONCLUSIONS: NMAR offers slightly better performance compared to TRMAR in streak reduction and image quality metrics. However, TRMAR is less susceptible to metal segmentation errors and can closely approximate the reduction in the streak metal artifact seen in NMAR at 1/3 the computation time. With the recent introduction of PCD-CT into the clinic, TRMAR offers notable potential for fast, effective MAR.

A detective quantum efficiency for spectroscopic X-ray imaging detectors.

PURPOSE: Spectroscopic X-ray detectors (SXDs) are under development for X-ray imaging applications. Recent efforts to extend the detective quantum efficiency (DQE) to SXDs impose a barrier to experimentation and/or do not provide a task-independent measure of detector performance. The purpose of this article is to define a task-independent DQE for SXDs that can be measured using a modest extension of established DQE-metrology methods. METHODS: We defined a task-independent spectroscopic DQE and performed a simulation study to determine the relationship between the zero-frequency DQE and the ideal-observer signal-to-noise ratio (SNR) of low-frequency soft-tissue, bone, iodine, and gadolinium signals. In our simulations, we used calibrated models of the spatioenergetic response of cadmium telluride (CdTe) and cadmium-zinc-telluride (CdZnTe) SXDs. We also measured the zero-frequency DQE of a CdTe detector with two energy bins and of a CdZnTe detector with up to six energy bins for an RQA9 spectrum and compared with model predictions. RESULTS: The spectroscopic DQE accounts for spectral distortions, energy-bin-dependent spatial resolution, interbin spatial noise correlations, and intrabin spatial noise correlations; it is mathematically equivalent to the squared SNR per unit fluence of the generalized least-squares estimate of the height of an X-ray impulse in a uniform noisy background. The zero-frequency DQE has a strong linear relationship with the ideal-observer SNR of low-frequency soft-tissue, bone, iodine, and gadolinium signals, and can be expressed in terms of the product of the quantum efficiency and a Swank noise factor that accounts for DQE degradation due to, for example, charge sharing (CS) and electronic noise. The spectroscopic Swank noise factor of the CdTe detector was measured to be 0.81 ± 0.04 and 0.83 ± 0.04 with and without anticoincidence logic for CS suppression, respectively. The spectroscopic Swank noise factor of the CdZnTe detector operated with four energy bins was measured to be 0.82 ± 0.02 which is within 5% of the theoretical value. CONCLUSIONS: The spectroscopic DQE defined here is (1) task-independent, (2) can be measured using a modest extension of existing DQE-metrology methods, and (3) is predictive of the ideal-observer SNR of soft-tissue, bone, iodine, and gadolinium signals. For CT applications, the combination of CS and electronic noise in CdZnTe spectroscopic detectors will degrade the zero-frequency DQE by 10 %-20 % depending on the electronic noise level and pixel size.

Temporary Membrane Permeabilization via the Pore-Forming Toxin Lysenin.

Pore-forming toxins are alluring tools for delivering biologically-active, impermeable cargoes to intracellular environments by introducing large conductance pathways into cell membranes. However, the lack of regulation often leads to the dissipation of electrical and chemical gradients, which might significantly affect the viability of cells under scrutiny. To mitigate these problems, we explored the use of lysenin channels to reversibly control the barrier function of natural and artificial lipid membrane systems by controlling the lysenin's transport properties. We employed artificial membranes and electrophysiology measurements in order to identify the influence of labels and media on the lysenin channel's conductance. Two cell culture models: Jurkat cells in suspension and adherent ATDC5 cells were utilized to demonstrate that lysenin channels may provide temporary cytosol access to membrane non-permeant propidium iodide and phalloidin. Permeability and cell viability were assessed by fluorescence spectroscopy and microscopy. Membrane resealing by chitosan or specific media addition proved to be an effective way of maintaining cellular viability. In addition, we loaded non-permeant dyes into liposomes via lysenin channels by controlling their conducting state with multivalent metal cations. The improved control over membrane permeability might prove fruitful for a large variety of biological or biomedical applications that require only temporary, non-destructive access to the inner environment enclosed by natural and artificial membranes.

Stochastic sensing of Angiotensin II with lysenin channels.

The ability of pore-forming proteins to interact with various analytes has found vast applicability in single molecule sensing and characterization. In spite of their abundance in organisms from all kingdoms of life, only a few pore-forming proteins have been successfully reconstituted in artificial membrane systems for sensing purposes. Lysenin, a pore-forming toxin extracted from the earthworm E. fetida, inserts large conductance nanopores in lipid membranes containing sphingomyelin. Here we show that single lysenin channels may function as stochastic nanosensors by allowing the short cationic peptide angiotensin II to be electrophoretically driven through the conducting pathway. Long-term translocation experiments performed using large populations of lysenin channels allowed unequivocal identification of the unmodified analyte by Liquid Chromatography-Mass Spectrometry. However, application of reverse voltages or irreversible blockage of the macroscopic conductance of lysenin channels by chitosan addition prevented analyte translocation. This investigation demonstrates that lysenin channels have the potential to function as nano-sensing devices capable of single peptide molecule identification and characterization, which may be further extended to other macromolecular analytes.