Quantification of multiple mixed contrast and tissue compositions using photon-counting spectral computed tomography.

Quantitative material decomposition of multiple mixed, or spatially coincident, contrast agent (gadolinium and iodine) and tissue (calcium and water) compositions is demonstrated using photon-counting spectral computed tomography (CT). Material decomposition is performed using constrained maximum likelihood estimation (MLE) in the image domain. MLE is calibrated by multiple linear regression of all pure material compositions, which exhibits a strong correlation ( R 2 > 0.91 ) between the measured x-ray attenuation in each photon energy bin and known concentrations in the calibration phantom. Material decomposition of mixed compositions in the sample phantom provides color material concentration maps that clearly identify and differentiate each material. The measured area under the receiver operating characteristic curve is > 0.95 , indicating highly accurate material identification. Material decomposition also provides accurate quantitative estimates of material concentrations in mixed compositions with a root-mean-squared error < 12 % of the maximum concentration for each material. Thus, photon-counting spectral CT enables quantitative molecular imaging of multiple spatially coincident contrast agent (gadolinium and iodine) and tissue (calcium and water) compositions, which is not possible with current clinical molecular imaging modalities, such as nuclear imaging and magnetic resonance imaging.

Nondestructive, longitudinal measurement of collagen scaffold degradation using computed tomography and gold nanoparticles.

Biodegradable materials, such as collagen scaffolds, are used extensively in clinical medicine for tissue regeneration and/or as an implantable drug delivery vehicle. However, available methods to study biomaterial degradation are typically invasive, destructive, and/or non-volumetric. Therefore, the objective of this study was to investigate a new method for nondestructive, longitudinal, and volumetric measurement of collagen scaffold degradation. Gold nanoparticles (Au NPs) were covalently conjugated to collagen fibrils during scaffold preparation to enable contrast-enhanced imaging of collagen scaffolds. The X-ray attenuation of as-prepared scaffolds increased linearly with increased Au NP concentration such that ≥60 mM Au NPs provided sufficient contrast to measure scaffold degradation. Collagen scaffold degradation kinetics were measured to increase during in vitro enzymatic degradation in media with an increased concentration of collagenase. The scaffold degradation kinetics measured by micro-CT exhibited lower variability compared with gravimetric measurement and were validated by measurement of the release of Au NPs from the same samples by optical spectroscopy. Thus, Au NPs and CT synergistically enabled nondestructive, longitudinal, and volumetric measurement of collagen scaffold degradation.

Exfoliated Graphene Leads to Exceptional Mechanical Properties of Polymer Composite Films.

Polymers with superior mechanical properties are desirable in many applications. In this work, polyethylene (PE) films reinforced with exfoliated thermally reduced graphene oxide (TrGO) fabricated using a roll-to-roll hot-drawing process are shown to have outstanding mechanical properties. The specific ultimate tensile strength and Young's modulus of PE/TrGO films increased monotonically with the drawing ratio and TrGO filler fraction, reaching up to 3.2 ± 0.5 and 109.3 ± 12.7 GPa, respectively, with a drawing ratio of 60× and a very low TrGO weight fraction of 1%. These values represent by far the highest reported to date for a polymer/graphene composite. Experimental characterizations indicate that as the polymer films are drawn, TrGO fillers are exfoliated, which is further confirmed by molecular dynamics (MD) simulations. Exfoliation increases the specific area of the TrGO fillers in contact with the PE matrix molecules. Molecular dynamics simulations show that the PE-TrGO interaction is stronger than the PE-PE intermolecular van der Waals interaction, which enhances load transfer from PE to TrGO and leverages the ultrahigh mechanical properties of TrGO.

The fracture toughness of small animal cortical bone measured using arc-shaped tension specimens: Effects of bisphosphonate and deproteinization treatments.

Small animal models, and especially transgenic models, have become widespread in the study of bone mechanobiology and metabolic bone disease, but test methods for measuring fracture toughness on multiple replicates or at multiple locations within a single small animal bone are lacking. Therefore, the objective of this study was to develop a method to measure cortical bone fracture toughness in multiple specimens and locations along the diaphysis of small animal bones. Arc-shaped tension specimens were prepared from the mid-diaphysis of rabbit ulnae and loaded to failure to measure the radial fracture toughness in multiple replicates per bone. The test specimen dimensions, crack length, and maximum load met requirements for measuring the plane strain fracture toughness. Experimental groups included a control group, bisphosphonate treatment group, and an ex vivo deproteinization treatment following bisphosphonate treatment (5 rabbits/group and 15 specimens/group). The fracture toughness of ulnar cortical bone from rabbits treated with zoledronic acid for six months exhibited no difference compared with the control group. Partially deproteinized specimens exhibited significantly lower fracture toughness compared with both the control and bisphosphonate treatment groups. The deproteinization treatment increased tissue mineral density (TMD) and resulted in a negative linear correlation between the measured fracture toughness and TMD. Fracture toughness measurements were repeatable with a coefficient of variation of 12-16% within experimental groups. Retrospective power analysis of the control and deproteinization treatment groups indicated a minimum detectable difference of 0.1MPa·m1/2. Therefore, the overall results of this study suggest that arc-shaped tension specimens offer an advantageous new method for measuring the fracture toughness in small animal bones.

Effects of calibration methods on quantitative material decomposition in photon-counting spectral computed tomography using a maximum a posteriori estimator.

PURPOSE: Advances in photon-counting detectors have enabled quantitative material decomposition using multi-energy or spectral computed tomography (CT). Supervised methods for material decomposition utilize an estimated attenuation for each material of interest at each photon energy level, which must be calibrated based upon calculated or measured values for known compositions. Measurements using a calibration phantom can advantageously account for system-specific noise, but the effect of calibration methods on the material basis matrix and subsequent quantitative material decomposition has not been experimentally investigated. Therefore, the objective of this study was to investigate the influence of the range and number of contrast agent concentrations within a modular calibration phantom on the accuracy of quantitative material decomposition in the image domain. METHODS: Gadolinium was chosen as a model contrast agent in imaging phantoms, which also contained bone tissue and water as negative controls. The maximum gadolinium concentration (30, 60, and 90 mM) and total number of concentrations (2, 4, and 7) were independently varied to systematically investigate effects of the material basis matrix and scaling factor calibration on the quantitative (root mean squared error, RMSE) and spatial (sensitivity and specificity) accuracy of material decomposition. Images of calibration and sample phantoms were acquired using a commercially available photon-counting spectral micro-CT system with five energy bins selected to normalize photon counts and leverage the contrast agent k-edge. Material decomposition of gadolinium, calcium, and water was performed for each calibration method using a maximum a posteriori estimator. RESULTS: Both the quantitative and spatial accuracy of material decomposition were most improved by using an increased maximum gadolinium concentration (range) in the basis matrix calibration; the effects of using a greater number of concentrations were relatively small in magnitude by comparison. The material basis matrix calibration was more sensitive to changes in the calibration methods than the scaling factor calibration. The material basis matrix calibration significantly influenced both the quantitative and spatial accuracy of material decomposition, while the scaling factor calibration influenced quantitative but not spatial accuracy. Importantly, the median RMSE of material decomposition was as low as ~1.5 mM (~0.24 mg/mL gadolinium), which was similar in magnitude to that measured by optical spectroscopy on the same samples. CONCLUSION: The accuracy of quantitative material decomposition in photon-counting spectral CT was significantly influenced by calibration methods which must therefore be carefully considered for the intended diagnostic imaging application.

Hafnia (HfO2) nanoparticles as an X-ray contrast agent and mid-infrared biosensor.

The interaction of hafnium oxide (HfO2) nanoparticles (NPs) with X-ray and mid-infrared radiation was investigated to assess the potential as a multifunctional diagnostic probe for X-ray computed tomography (CT) and/or mid-infrared biosensing. HfO2 NPs of controlled size were prepared by a sol-gel process and surface functionalized with polyvinylpyrrolidone, resulting in relatively spherical and monodispersed NPs with a tunable mean diameter in the range of ∼7-31 nm. The X-ray attenuation of HfO2 NPs was measured over 0.5-50 mM concentration and compared with Au NPs and iodine, which are the most prominent X-ray contrast agents currently used in research and clinical diagnostic imaging, respectively. At clinical CT tube potentials >80 kVp, HfO2 NPs exhibited superior or similar X-ray contrast compared to Au NPs, while both exhibited significantly greater X-ray contrast compared to iodine, due to the favorable location of the k-shell absorption edge for hafnium and gold. Moreover, energy-dependent differences in X-ray attenuation enabled simultaneous quantitative molecular imaging of each agent using photon-counting spectral (multi-energy) CT. HfO2 NPs also exhibited a strong mid-infrared absorption in the Reststrahlen band from ∼250-800 cm(-1) and negative permittivity below 695 cm(-1), which can enable development of mid-infrared biosensors and contrast agents, leveraging surface enhanced mid-infrared and/or phonon polariton absorption.

Fabrication and Short-Term in Vivo Performance of a Natural Elastic Lamina-Polymeric Hybrid Vascular Graft.

Although significant advances have been made in the development of artificial vascular grafts, small-diameter grafts still suffer from excessive platelet activation, thrombus formation, smooth muscle cell intimal hyperplasia, and high occurrences of restenosis. Recent discoveries demonstrating the excellent blood-contacting properties of the natural elastic lamina have raised the possibility that an acellular elastic lamina could effectively serve as a patent blood-contacting surface in engineered vascular grafts. However, the elastic lamina alone lacks the requisite mechanical properties to function as a viable vascular graft. Here, we have screened a wide range of biodegradable and biostable medical-grade polymers for their ability to adhere to the outer surface of the elastic lamina and allow cellular repopulation following engraftment in the rat abdominal aorta. We demonstrate a novel method for the fabrication of elastic lamina-polymeric hybrid small-diameter vascular grafts and identify poly(ether urethane) (PEU 1074A) as ideal for this purpose. In vivo results demonstrate graft patency over 21 days, with low thrombus formation, mild inflammation, and the general absence of smooth muscle cell hyperplasia on the graft's luminal surface. The results provide a new direction for developing small-diameter vascular grafts that are mass-producible, shelf-stable, and universally compatible due to a lack of immune response and inhibit the in-graft restenosis response that is common to nonautologous materials.