Accuracy of volumetric bone mineral density measurement in weight bearing, cone beam computed tomography.

BACKGROUND: Weight bearing computed tomography (WBCT) utilizes cone beam CT technology to provide assessments of lower limb joint structures while they are functionally loaded. Grey-scale values indicative of X-ray attenuation that are output from cone beam CT are challenging to calibrate, and their use for bone mineral density (BMD) measurement remains debatable. To determine whether WBCT can be reliably used for cortical and trabecular BMD assessment, we sought to establish the accuracy of BMD measurements at the knee using modern WBCT by comparing them to measurements from conventional CT. METHODS: A hydroxyapatite phantom with three inserts of varying densities was used to systematically quantify signal uniformity and BMD accuracy across the acquisition volume. We evaluated BMD in vivo (n = 5, female) using synchronous and asynchronous calibration techniques in WBCT and CT. To account for variation in attenuation along the height (z-axis) of acquisition volumes, we tested a height-dependent calibration approach for both WBCT and CT images. RESULTS: Phantom BMD measurement error in WBCT was as high as 15.3% and consistently larger than CT (up to 5.6%). Phantom BMD measures made under synchronous conditions in WBCT improved measurement accuracy by up to 3% but introduced more variability in measured BMD. We found strong correlations (R = 0.96) as well as wide limits of agreement (-324 mgHA/cm3 to 183 mgHA/cm3) from Bland-Altman analysis between WBCT and CT measures in vivo that were not improved by height-dependent calibration. CONCLUSION: Whilst BMD accuracy from WBCT was found to be dependent on apparent density, accuracy was independent of the calibration technique (synchronous or asynchronous) and the location of the measurement site within the field of view. Overall, we found strong correlations between BMD measures from WBCT and CT and in vivo measures to be more accurate in trabecular bone regions. Importantly, WBCT can be used to distinguish between anatomically relevant differences in BMD, however future work is necessary to determine the repeatability and sensitivity of BMD measures in WBCT.

Analysis of Hand Joint Space Morphology in Women and Men with Hereditary Hemochromatosis.

Hereditary hemochromatosis (HH) causes unbalanced iron deposition in many organs including the joints leading to severe cartilage loss and bone damage in the metacarpophalangeal joints (MCPJ). High-resolution peripheral quantitative computed tomography (HR-pQCT) and its joint space width (JSW) quantification algorithm quantifies in vivo 3D joint morphology. We therefore aimed to (i) determine feasibility and performance of the JSW algorithm in HH, (ii) quantify joint space morphology, and (iii) investigate the relationship between morphological and clinical parameters in HH. Here, we performed an exploratory study on 24 HH patients and sex- and age-matched controls using HR-pQCT imaging of MCPJ. Mineralized bone structure was automatically segmented from the grayscale image data and periosteal surface bone masks and joint space masks were generated. Mean, minimal, and maximal joint space width (JSW; JSW.MIN; JSW.MAX), JSW heterogeneity (JSW.SD), JSW asymmetry (JSW.AS), and joint space volume (JSV) were computed. Demographics and, for HH patients, disease-specific parameters were recorded. Segmentation of JS was very good with 79.7% of MCPJs successfully segmented at first attempt and 20.3% requiring semi-manual correction. HH men showed larger JSV at all MCPs (+ 25.4% < JSV < + 41.8%, p < 0.05), larger JSW.MAX at MCP 3-4 (+ 14%, 0.006 < p < 0.062), and wider JSW (+ 13%, p = 0.043) at MCP 4 relative to HH women. Compared to controls, both HH men and HH women showed larger JSW.AS and smaller JSW.MIN at all MCP levels, reaching significance for HH men at MCP 2 and 3 (JSW.AS: + 323% < JSW.AS < + 359%, 0.020 < p < 0.043; JSW.MIN: - 216% < JSW.MIN < - 225%, p < 0.043), and for women at MCP 3 (JSW.AS: + 180%, p = 0.025; JSW.MIN: - 41.8%, p = 0.022). Time since HH diagnosis was correlated positively with MCP 4 JSW.AS and JSW.SD (0.463 < ρ < 0.499, p < 0.040), and the number of phlebotomies since diagnosis was correlated with JSW.SD at all MCPs (0.432 < ρ < 0.535, p < 0.050). HR-pQCT-based JSW quantification in MCPJ of HH patients is feasible, performs well even in narrow JS, and allows to define the microstructural joint burden of HH.

Reproducibility and repeatability of a semi-automated pipeline to quantify trapeziometacarpal joint angles using dynamic computed tomography.

BACKGROUND: The trapeziometacarpal (TMC) joint is a mechanically complex joint and is commonly affected by musculoskeletal diseases such as osteoarthritis. Quantifying in vivo TMC joint biomechanics, such as joint angles, with traditional reflective marker-based methods can be difficult due to the joint's location in the hand. Dynamic computed tomography (CT) can facilitate the quantification of TMC joint motion by continuously capturing three-dimensional volumes over time. However, post-processing of dynamic CT datasets can be time intensive and automated methods are needed to reduce processing times to allow for application to larger clinical studies. The purpose of this work is to introduce a fast, semi-automated pipeline to quantify joint angles from dynamic CT scans of the TMC joint and evaluate the associated error in joint angle and translation computation by means of a reproducibility and repeatability study. METHODS: Ten cadaveric hands were scanned with dynamic CT using a passive motion device to move thumbs in a radial abduction-adduction motion. Static CT scans and high-resolution peripheral quantitative CT scans were also acquired to generate high-resolution bone meshes. Abduction-adduction, flexion-extension, and axial rotation angles were computed using a joint coordinate system. Reproducibility and repeatability were assessed using intraclass correlation coefficients, Bland-Altman analysis, and root mean square errors. Target registration errors were computed to evaluate errors associated with image registration. RESULTS: We found good repeatability for flexion-extension, abduction-adduction, and axial rotation angles. Reproducibility was moderate for all three angles. Joint translations exhibited greater repeatability than reproducibility. Specimens with greater joint degeneration had lower repeatability and reproducibility. We found that the difference in resulting joint angles and translations were likely due to differences in segment coordinate system definition between multiple raters, rather than due to registration errors. CONCLUSIONS: The proposed semi-automatic processing pipeline was fast, repeatable, and moderately reproducible when quantifying TMC joint angles and translations. This work provides a range of errors for TMC joint angles from dynamic CT scans using manually selected anatomical landmarks.

Advancements in Osteoporosis Imaging, Screening, and Study of Disease Etiology.

PURPOSE OF REVIEW: The purpose of this review is to inform researchers and clinicians with the most recent imaging techniques that are employed (1) to opportunistically screen for osteoporosis and (2) to provide a better understanding into the disease etiology of osteoporosis. RECENT FINDINGS: Phantomless calibration techniques for computed tomography (CT) may pave the way for better opportunistic osteoporosis screening and the retroactive analysis of imaging data. Additionally, hardware advances are enabling new applications of dual-energy CT and cone-beam CT to the study of bone. Advances in MRI sequences are also improving imaging evaluation of bone properties. Finally, the application of image registration techniques is enabling new uses of imaging to investigate soft tissue-bone interactions as well as bone turnover. While DXA remains the most prominent imaging tool for osteoporosis diagnosis, new imaging techniques are becoming more widely available and providing additional information to inform clinical decision-making.

Evaluating high-resolution computed tomography derived 3-D joint space metrics of the metacarpophalangeal joints between rheumatoid arthritis and age- and sex-matched control participants.

Introduction: Rheumatoid arthritis (RA) is commonly characterized by joint space narrowing. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides unparalleled in vivo visualization and quantification of joint space in extremity joints commonly affected by RA, such as the 2nd and 3rd metacarpophalangeal joints. However, age, sex, and obesity can also influence joint space narrowing. Thus, this study aimed to determine whether HR-pQCT joint space metrics could distinguish between RA patients and controls, and determine the effects of age, sex and body mass index (BMI) on these joint space metrics. Methods: HR-pQCT joint space metrics (volume, width, standard deviation of width, maximum/minimum width, and asymmetry) were acquired from RA patients and age-and sex-matched healthy control participants 2nd and 3rd MCP joints. Joint health and functionality were assessed with ultrasound (i.e., effusion and inflammation), hand function tests, and questionnaires. Results: HR-pQCT-derived 3D joint space metrics were not significantly different between RA and control groups (p > 0.05), despite significant differences in inflammation and joint function (p < 0.05). Joint space volume, mean joint space width (JSW), maximum JSW, minimum JSW were larger in males than females (p < 0.05), while maximum JSW decreased with age. No significant association between joint space metrics and BMI were found. Conclusion: HR-pQCT did not detect group level differences between RA and age-and sex-matched controls. Further research is necessary to determine whether this is due to a true lack of group level differences due to well-controlled RA, or the inability of HR-pQCT to detect a difference.

Bioavailability, toxicity and biotransformation of selenium in midge (Chironomus dilutus) larvae exposed via water or diet to elemental selenium particles, selenite, or selenized algae.

Elemental selenium (Se) is generally considered to be biologically inert due to its insolubility in water. It is a common form of Se in sediment near uranium mining and milling operations in northern Saskatchewan, Canada. Nanosized particles of many materials exhibit different properties compared with their bulk phases, in some cases posing health and ecological risks. Here we investigated the bioavailability and toxicity of Se nanoparticles (SeNPs) using 10-day waterborne and dietary exposures to larvae of Chironomus dilutus, a common benthic invertebrate. For comparison, larvae were also exposed to waterborne dissolved selenite and to dietary selenomethionine as selenized algae. Larval Se accumulation was evaluated using graphite furnace atomic absorption spectroscopy or inductively coupled plasma mass spectroscopy for total Se and X-ray absorption spectroscopy for Se chemical speciation. Exposure to nanoparticulate Se resulted in Se bioaccumulation, at high concentrations, inhibiting larval growth in both waterborne and dietary exposures; larvae predominantly accumulated selenomethionine-like species regardless of uptake route or form of Se tested. Despite the observed Se accumulation, our findings suggest there is little risk of direct SeNP toxicity to benthic invertebrates in Se-contaminated sediments in northern Saskatchewan. Nevertheless, elemental Se in sediments may be biologically available and may contribute directly or indirectly to the risk of Se toxicity to egg-laying vertebrates (fish and piscivorous birds) in Se-contaminated aquatic systems. It thus may be necessary to include elemental Se as a source of potential Se exposure in ecological risk assessments.

Addressing Challenges of Opportunistic Computed Tomography Bone Mineral Density Analysis.

Computed tomography (CT) offers advanced biomedical imaging of the body and is broadly utilized for clinical diagnosis. Traditionally, clinical CT scans have not been used for volumetric bone mineral density (vBMD) assessment; however, computational advances can now leverage clinically obtained CT data for the secondary analysis of bone, known as opportunistic CT analysis. Initial applications focused on using clinically acquired CT scans for secondary osteoporosis screening, but opportunistic CT analysis can also be applied to answer research questions related to vBMD changes in response to various disease states. There are several considerations for opportunistic CT analysis, including scan acquisition, contrast enhancement, the internal calibration technique, and bone segmentation, but there remains no consensus on applying these methods. These factors may influence vBMD measures and therefore the robustness of the opportunistic CT analysis. Further research and standardization efforts are needed to establish a consensus and optimize the application of opportunistic CT analysis for accurate and reliable assessment of vBMD in clinical and research settings. This review summarizes the current state of opportunistic CT analysis, highlighting its potential and addressing the associated challenges.

Erosion Identification in Metacarpophalangeal Joints in Rheumatoid Arthritis using High-Resolution Peripheral Quantitative Computed Tomography.

Bone erosions are a pathological feature of several forms of inflammatory arthritis including rheumatoid arthritis (RA). The increased presence and size of erosions are associated with poor outcomes, joint function, and disease progression. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides unparalleled in vivo visualization of bone erosions. However, at this resolution, discontinuities in the cortical shell (cortical breaks) that are associated with normal physiological processes and pathology are also visible. The Study grouP for xtrEme Computed Tomography in Rheumatoid Arthritis previously used a consensus process to develop a definition of pathological erosion in HR-pQCT: a cortical break detected in at least two consecutive slices, in at least two perpendicular planes, non-linear in shape, with underlying trabecular bone loss. However, despite the availability of a consensus definition, erosion identification is a demanding task with challenges in inter-rater variability. The purpose of this work is to introduce a training tool to provide users with guidance on identifying pathological cortical breaks on HR-pQCT images for erosion analysis. The protocol presented here uses a custom-built module (Bone Analysis Module (BAM) - Training), implemented as an extension to an open-source image processing software (3D Slicer). Using this module, users can practice identifying erosions and compare their results to erosions annotated by expert rheumatologists.

Assessing the Sensitivity of Dual-Energy Computed Tomography 3-Material Decomposition for the Detection of Gout.

OBJECTIVES: The aim of this study was to assess the accuracy and precision of a novel application of 3-material decomposition (3MD) with virtual monochromatic images (VMIs) in the dual-energy computed tomography (DECT) assessment of monosodium urate (MSU) and hydroxyapatite (HA) phantoms compared with a commercial 2-material decomposition (2MD) and dual-thresholding (DT) material decomposition methods. MATERIALS AND METHODS: Monosodium urate (0.0, 3.4, 13.3, 28.3, and 65.2 mg/dL tubes) and HA (100, 400, and 800 mg/cm 3 tubes) phantoms were DECT scanned individually and together in the presence of the foot and ankle of 15 subjects. The raw data were decomposed with 3MD-VMI, 2MD, and DT to produce MSU-only and HA-only images. Mean values of 10 × 10 × 10-voxel volumes of interest (244 µm 3 ) placed in each MSU and HA phantom well were obtained and compared with their known concentrations and across measurements with subjects' extremities to obtain accuracy and precision measures. A statistical difference was considered significant if P < 0.05. RESULTS: Compared with known phantom standards, 3MD-VMI was accurate for the detection of MSU concentrations as low as 3.4 mg/dL ( P = 0.75). In comparison, 2MD was limited to 13.3 mg/dL ( P = 0.06) and DT was unable to detect MSU concentrations below 65.2 mg/L ( P = 0.16). For the HA phantom, 3MD-VMI and 2MD were accurate for all concentrations including the lowest at 100 mg/cm 3 ( P = 0.63 and P = 0.55, respectively). Dual-thresholding was not useful for the decomposition of HA phantom. Precision was high for both 3MD-VMI and 2MD measurements for both MSU and HA phantoms. Qualitatively, 3MD-VMI MSU-only images demonstrated reduced beam-hardening artifact and voxel misclassification, compared with 2MD and DT. CONCLUSIONS: Three-material decomposition-VMI DECT is accurate for quantification of MSU and HA concentrations in phantoms and accurately detects a lower concentration of MSU than either 2MD or DT. For concentration measurements of both MSU and HA phantoms, 3MD-VMI and 2MD have high precision, but DT had limitations. Clinical implementation of 3MD-VMI DECT promises to improve the performance of this imaging modality for diagnosis and treatment monitoring of gout.

Internal calibration for opportunistic computed tomography muscle density analysis.

INTRODUCTION: Muscle weakness can lead to reduced physical function and quality of life. Computed tomography (CT) can be used to assess muscle health through measures of muscle cross-sectional area and density loss associated with fat infiltration. However, there are limited opportunities to measure muscle density in clinically acquired CT scans because a density calibration phantom, allowing for the conversion of CT Hounsfield units into density, is typically not included within the field-of-view. For bone density analysis, internal density calibration methods use regions of interest within the scan field-of-view to derive the relationship between Hounsfield units and bone density, but these methods have yet to be adapted for muscle density analysis. The objective of this study was to design and validate a CT internal calibration method for muscle density analysis. METHODOLOGY: We CT scanned 10 bovine muscle samples using two scan protocols and five scan positions within the scanner bore. The scans were calibrated using internal calibration and a reference phantom. We tested combinations of internal calibration regions of interest (e.g., air, blood, bone, muscle, adipose). RESULTS: We found that the internal calibration method using two regions of interest, air and adipose or blood, yielded accurate muscle density values (< 1% error) when compared with the reference phantom. The muscle density values derived from the internal and reference phantom calibration methods were highly correlated (R2 > 0.99). The coefficient of variation for muscle density across two scan protocols and five scan positions was significantly lower for internal calibration (mean = 0.33%) than for Hounsfield units (mean = 6.52%). There was no difference between coefficient of variation for the internal calibration and reference phantom methods. CONCLUSIONS: We have developed an internal calibration method to produce accurate and reliable muscle density measures from opportunistic computed tomography images without the need for calibration phantoms.

Open-source image analysis tool for the identification and quantification of cortical interruptions and bone erosions in high-resolution peripheral quantitative computed tomography images of patients with rheumatoid arthritis.

Identification of bone erosions and quantification of erosion volume is important for rheumatoid arthritis diagnosis, and can add important information to evaluate disease progression and treatment effects. High-resolution peripheral quantitative computed tomography (HR-pQCT) is well suited for this purpose, however analysis methods are not widely available. The purpose of this study was to develop an open-source software tool for the identification and quantification of bone erosions using images acquired by HR-pQCT. The collection of modules, Bone Analysis Modules (BAM) - Erosion, implements previously published erosion analysis techniques as modules in 3D Slicer, an open-source image processing and visualization tool. BAM includes a module to automatically identify cortical interruptions, from which erosions are manually selected, and a hybrid module that combines morphological and level set operations to quantify the volume of bone erosions. HR-pQCT images of the second and third metacarpophalangeal (MCP) joints were acquired in patients with RA (XtremeCT, n = 14, XtremeCTII, n = 22). The number of cortical interruptions detected by BAM-Erosion agreed strongly with the previously published cortical interruption detection algorithm for both XtremeCT (r2 = 0.85) and XtremeCTII (r2 = 0.87). Erosion volume assessment by BAM-Erosion agreed strongly (r2 = 0.95) with the Medical Image Analysis Framework. BAM-Erosion provides an open-source erosion analysis tool that produces comparable results to previously published algorithms, with improved options for visualization. The strength of the tool is that it implements multiple image processing algorithms for erosion analysis on a single, widely available, open-source platform that can accommodate future updates.

Use of Soller slits to remove reference foil fluorescence from transmission spectra.

Measurement of X-ray absorption spectroscopy (XAS) in transmission is the method of choice for strong or concentrated samples. In a typical XAS experiment above 5 keV the sample is placed between the first (I(0)) and second (I(1)) ion chambers and a standard foil is placed between the second (I(1)) and third (I(2)) ion chambers for simultaneous calibration of energy during sample analysis. However, some fluorescence from the foil may be registered in I(1), causing anomalies in the transmission signal of the sample, especially when the sample edge jump is relatively small. To remedy this, Soller slits were constructed and placed between the foil and I(1) to minimize back-fluorescence from the foil. A comparison of blank and standard samples, measured with or without Soller slits or under a worst-case scenario, demonstrates the advantages of Soller slits when analyzing weak signal samples via transmission XAS.

Evaluating the trophic transfer of selenium in aquatic ecosystems using caged fish, X-ray absorption spectroscopy and stable isotope analysis.

This research evaluated the dominant exposure pathways with regard to the bioaccumulation and trophic transfer of selenium (Se) in caged small-bodied fish inhabiting the receiving waters of a uranium-processing mill in northern Saskatchewan, Canada. A 21-day cage study was conducted using wild naïve lake chub (Couesius plumbeus) collected from a reference lake and caged in a reference and an exposure lake downstream of the mill discharge. Caged fish were fed commercially produced Chironomus spp. diets of 1.5 (basal - commercial food) and 5.5 (lab reared in Se-spiked water) µgSe/g (dry weight) at a feeding ration of 10 percent percent body weight/day. Lake chub fed the Se-spiked diet and caged in the reference lake showed increased whole-body Se concentrations compared to chub fed the basal diet after 21 days. Lake chub caged in the exposure lake from both the elevated Se and basal diet groups had significantly greater whole-body Se concentrations compared to the reference lake, and were not significantly different from each other. The use of stable carbon (C), nitrogen (N), and sulphur (S) isotope analyses indicated that alternate benthic food sources native to the exposure lake were likely consumed in conjunction with the controlled diets. Stable isotope analysis of both wild and caged lake chub indicated that the N and S isotopic signatures decreased with increasing Se exposure, which was reflective of the differences in isotopic signatures of the food sources. Dose-dependent substitution of Se for S in methionine as a consequence of dietary Se exposure was illustrated by a decreasing whole-body S isotope signature and an increasing proportion of selenomethionine-like compounds (as measured by synchrotron-based X-ray absorption spectroscopy) with increasing Se exposure. Speciation results from caged lake chub indicated that Se substituted for S in methionine was the dominant Se species found in caged lake chub exposed to dietary sources of Se.

A quantitative assessment of dual energy computed tomography-based material decomposition for imaging bone marrow edema associated with acute knee injury.

PURPOSE: This study developed methods to quantify and improve the accuracy of dual-energy CT (DECT)-based bone marrow edema imaging using a clinical CT system. Objectives were: (a) to quantitatively compare DECT with gold-standard, fluid-sensitive MRI for imaging of edema-like marrow signal intensity (EMSI) and (b) to identify image analysis parameters that improve delineation of EMSI associated with acute knee injury on DECT images. METHODS: DECT images from ten participants with acute knee injury were decomposed into estimated fractions of bone, healthy marrow, and edema based on energy-dependent differences in tissue attenuation. Fluid-sensitive MR images were registered to DECT for quantitative, voxel-by-voxel comparison between the two modalities. An optimization scheme was developed to find attenuation coefficients for healthy marrow and edema that improved EMSI delineation, compared to MRI. DECT method accuracy was evaluated by measuring dice coefficients, mutual information, and normalized cross correlation between the DECT result and registered MRI. RESULTS: When applying the optimized three-material decomposition method, dice coefficients for EMSI identified through DECT vs MRI were 0.32 at the tibia and 0.13 at the femur. Optimization of attenuation coefficients improved dice coefficient, mutual information, and cross-correlation between DECT and gold-standard MRI by 48%-107% compared to three-material decomposition using non-optimized parameters, and improved mutual information and cross-correlation by 39%-58% compared to the manufacturer-provided two-material decomposition. CONCLUSIONS: This study quantitatively evaluated the performance of DECT in imaging knee injury-associated EMSI and identified a method to optimize DECT-based visualization of complex tissues (marrow and edema) whose attenuation parameters cannot be easily characterized. Further studies are needed to improve DECT-based EMSI imaging at the femur.

Multi-Modal Imaging to Assess the Interaction Between Inflammation and Bone Damage Progression in Inflammatory Arthritis.

Combining results from multiple imaging techniques (i.e., multi-modal imaging) through image registration can result in the better characterization of joint tissue characteristics. In the context of inflammatory arthritis conditions, high-resolution peripheral quantitative computed tomography (HR-pQCT) provides excellent bone contrast while magnetic resonance imaging (MRI) provides superior contrast and resolution of soft tissue and inflammatory characteristics. Superimposing these imaging results upon each other provides a robust characterization of the joint. In a preliminary study of nine rheumatoid arthritis (RA) participants in clinical remission, we acquired HR-pQCT and MR images of their 2nd and 3rd metacarpophalangeal (MCP) joints at two timepoints 6 months apart. We present the benefits of a multi-modal imaging approach, in which we demonstrate the ability to localize regions of inflammation with subtle changes in bone erosion volume. Using HR-pQCT and MRI to visualize bone damage and inflammation, respectively, will improve our understanding of the impact that subclinical inflammation has on bone damage progression, and demonstrating if bone repair occurs where inflammation is resolved. The presented multi-modal imaging technique has the potential to study the progression of bone damage in relation to inflammation that otherwise would not be possible with either imaging technique alone. The multi-modal image registration technique will be helpful to understanding the development and pathogenesis of RA-associated bone erosions. Additionally, multi-modal imaging may provide a technique to probe the tissue-level changes that occur as a result of treatment regimes.

High-Resolution Peripheral Quantitative Computed Tomography for Bone Evaluation in Inflammatory Rheumatic Disease.

High resolution peripheral quantitative computed tomography (HR-pQCT) is a 3-dimensional imaging modality with superior sensitivity for bone changes and abnormalities. Recent advances have led to increased use of HR-pQCT in inflammatory arthritis to report quantitative volumetric measures of bone density, microstructure, local anabolic (e.g., osteophytes, enthesiophytes) and catabolic (e.g., erosions) bone changes and joint space width. These features may be useful for monitoring disease progression, response to therapy, and are responsive to differentiating between those with inflammatory arthritis conditions and healthy controls. We reviewed 69 publications utilizing HR-pQCT imaging of the metacarpophalangeal (MCP) and/or wrist joints to investigate arthritis conditions. Erosions are a marker of early inflammatory arthritis progression, and recent work has focused on improvement and application of techniques to sensitively identify erosions, as well as quantifying erosion volume changes longitudinally using manual, semi-automated and automated methods. As a research tool, HR-pQCT may be used to detect treatment effects through changes in erosion volume in as little as 3 months. Studies with 1-year follow-up have demonstrated progression or repair of erosions depending on the treatment strategy applied. HR-pQCT presents several advantages. Combined with advances in image processing and image registration, individual changes can be monitored with high sensitivity and reliability. Thus, a major strength of HR-pQCT is its applicability in instances where subtle changes are anticipated, such as early erosive progression in the presence of subclinical inflammation. HR-pQCT imaging results could ultimately impact decision making to uptake aggressive treatment strategies and prevent progression of joint damage. There are several potential areas where HR-pQCT evaluation of inflammatory arthritis still requires development. As a highly sensitive imaging technique, one of the major challenges has been motion artifacts; motion compensation algorithms should be implemented for HR-pQCT. New research developments will improve the current disadvantages including, wider availability of scanners, the field of view, as well as the versatility for measuring tissues other than only bone. The challenge remains to disseminate these analysis approaches for broader clinical use and in research.

Corrigendum to "Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging".

[This corrects the article DOI: 10.1155/2017/7368384.].

Dual-energy computed tomography using a gantry-based preclinical cone-beam microcomputed tomography scanner.

Dual-energy microcomputed tomography (DECT) can provide quantitative information about specific materials of interest, facilitating automated segmentation, and visualization of complex three-dimensional tissues. It is possible to implement DECT on currently available preclinical gantry-based cone-beam micro-CT scanners; however, optimal decomposition image quality requires customized spectral shaping (through added filtration), optimized acquisition protocols, and elimination of misregistration artifacts. We present a method for the fabrication of customized x-ray filters-in both shape and elemental composition-needed for spectral shaping. Fiducial markers, integrated within the sample holder, were used to ensure accurate co-registration between sequential low- and high-energy image volumes. The entire acquisition process was automated through the use of a motorized filter-exchange mechanism. We describe the design, implementation, and evaluation of a DECT system on a gantry-based-preclinical cone-beam micro-CT scanner.

Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging.

Micro-computed tomography (micro-CT) facilitates the visualization and quantification of contrast-enhanced microvessels within intact tissue specimens, but conventional preclinical vascular contrast agents may be inadequate near dense tissue (such as bone). Typical lead-based contrast agents do not exhibit optimal X-ray absorption properties when used with X-ray tube potentials below 90 kilo-electron volts (keV). We have developed a high-atomic number lanthanide (erbium) contrast agent, with a K-edge at 57.5 keV. This approach optimizes X-ray absorption in the output spectral band of conventional microfocal spot X-ray tubes. Erbium oxide nanoparticles (nominal diameter < 50 nm) suspended in a two-part silicone elastomer produce a perfusable fluid with viscosity of 19.2 mPa-s. Ultrasonic cavitation was used to reduce aggregate sizes to <70 nm. Postmortem intact mice were perfused to investigate the efficacy of contrast agent. The observed vessel contrast was >4000 Hounsfield units, and perfusion of vessels < 10 µm in diameter was demonstrated in kidney glomeruli. The described new contrast agent facilitated the visualization and quantification of vessel density and microarchitecture, even adjacent to dense bone. Erbium's K-edge makes this contrast agent ideally suited for both single- and dual-energy micro-CT, expanding potential preclinical research applications in models of musculoskeletal, oncological, cardiovascular, and neurovascular diseases.

Compound speckle model detects anti-angiogenic tumor response in preclinical nonlinear contrast-enhanced ultrasonography.

PURPOSE: This paper proposes a method for analyzing the first-order speckle statistics of nonlinear contrast-enhanced ultrasound images from tumors. METHODS: Contrast signal intensity is modeled as a compound distribution of exponential probability density functions with a gamma weighting function. The gamma probability weighting function serves as an approximation for log-normally distributed flow velocities in a vascular network. The model was applied to sub-harmonic bolus-injection images acquired from a mouse breast cancer xenograft model treated with murine version bevacizumab. RESULTS: The area under curve produced using the compound statistical model could more accurately discriminate anti-VEGF-treated tumors from untreated tumors than conventional contrast-enhanced ultrasound image processing. This result was validated with gold standard histological measures of microvascular density. Fractal vessel geometry was estimated using the gamma weighting function and tested against micro-CT perfusion casting. Treated tumors had a significantly lower vascular fractal dimension than control tumors. Vascular complexity estimated using the ultrasound compound statistical model performed similarly to micro-CT fractal dimension for discriminating treated from control tumors. CONCLUSION: The proposed technique can quantify tumor perfusion and provide an index of vascular complexity, making it a potentially useful addition for clinical detection of vascular normalization in anti-angiogenic trials.