An Environmental Scan and Appraisal of Patient Online Resources for Managing Rheumatoid Arthritis Flares.

OBJECTIVE: To conduct an environmental scan and appraisal of online patient resources to support rheumatoid arthritis (RA) flare self-management. METHODS: We used the Google search engine (last search March 2023) using the terms "rheumatoid arthritis" and "flare management." Additional searches targeted major arthritis organizations, as well as regional, national, and international resources. Appraisal of the resources was conducted by 2 research team members and 1 patient partner to assess the understandability and actionability of the resource using the Patient Education Materials Assessment Tool (PEMAT). Resources rating ≥ 60% in both domains by either the research team or the patient partner were further considered for content review. During content review, resources were excluded if they contained product advertisements, inaccurate information, or use of noninclusive language. If content review criteria were met, resources were designated as "highly recommended" if both patient partners and researchers' PEMAT ratings were ≥ 60%. If PEMAT ratings were divergent and had a rating ≥ 60% from only 1 group of reviewers, the resource was designated "acceptable." RESULTS: We identified 44 resources; 12 were excluded as they did not pass the PEMAT assessment. Fourteen resources received ratings ≥ 60% on understandability and actionability from both researchers and patient partners; 10 of these were retained following content review as "highly recommended" flare resources. Of the 18 divergent PEMAT ratings, 8 resources were retained as "acceptable" following content review. CONCLUSION: There is high variability in the actionability and understandability of online RA flare materials; only 23% of resources were highly recommended by researchers and patient partners.

Investigating the influence of patient eligibility characteristics on the number of deferrable rheumatologist visits: planning for a patient-initiated follow-up (PIFU) strategy.

OBJECTIVE: Patient-initiated follow-up (PIFU) for rheumatoid arthritis (RA) is a model of care delivery wherein patients contact the clinic when needed instead of regularly scheduled followups. Our objective was to investigate the influence of different patient eligibility characteristics on the number of potentially deferred visits to inform future implementation of a PIFU strategy. METHODS: We conducted a retrospective chart review of seven rheumatologists' practices at two university-based clinics between 01/03/2021-28/02/2022. Data extracted included the type and frequency of visits, disease management, comorbidities, and care complexities. Stable disease was defined as remission or low-disease activity with no medication changes at all visits. The influence of patient characteristics on the number of deferrable visits in patients with stable disease was explored in four criteria sets that were based on: early disease duration, medication prescribed, presence of care complexity elements, and comorbidity burden. RESULTS: Records from 770 visits were reviewed from 365 RA patients (71.5% female, 70.0% seropositive). Among all criteria sets, the proportion of visits that could be redirected varied between 2.5%-20.9%. The highest proportion of deferrable visits was achieved when eligibility criteria included only stable disease activity and RA patients on conventional synthetic disease modifying drugs or no medications (n=161, 20.9%). CONCLUSION: PIFU may result in a more efficient use of specialist healthcare resources. However, the applicability of such models of care and the number of deferred visits is highly dependent on patient characteristics used to establish eligibility criteria for that model. These findings should be considered when planning implementation trials.

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.

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.

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.

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.

Hip Fractures in Older Adults Are Associated With the Low Density Bone Phenotype and Heterogeneous Deterioration of Bone Microarchitecture.

Femoral neck areal bone mineral density (FN aBMD) is a key determinant of fracture risk in older adults; however, the majority of individuals who have a hip fracture are not considered osteoporotic according to their FN aBMD. This study uses novel tools to investigate the characteristics of bone microarchitecture that underpin bone fragility. Recent hip fracture patients (n = 108, 77% female) were compared with sex- and age-matched controls (n = 216) using high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging of the distal radius and tibia. Standard morphological analysis of bone microarchitecture, micro-finite element analysis, and recently developed techniques to identify void spaces in bone microarchitecture were performed to evaluate differences between hip fracture patients and controls. In addition, a new approach for phenotyping bone microarchitecture was implemented to evaluate whether hip fractures in males and females occur more often in certain bone phenotypes. Overall, hip fracture patients had notable deterioration of bone microarchitecture and reduced bone mineral density compared with controls, especially at weight-bearing sites (tibia and femoral neck). Hip fracture patients were more likely to have void spaces present at either site and had void spaces that were two to four times larger on average when compared with non-fractured controls (p < 0.01). Finally, bone phenotyping revealed that hip fractures were significantly associated with the low density phenotype (p < 0.01), with the majority of patients classified in this phenotype (69%). However, female and male hip fracture populations were distributed differently across the bone phenotype continuum. These findings highlight how HR-pQCT can provide insight into the underlying mechanisms of bone fragility by using information about bone phenotypes and identification of microarchitectural defects (void spaces). The added information suggests that HR-pQCT can have a beneficial role in assessing the severity of structural deterioration in bone that is associated with osteoporotic hip fractures. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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.

Diagnostic accuracy of a dual-energy computed tomography-based post-processing method for imaging bone marrow edema following an acute ligamentous knee injury.

OBJECTIVE: This study evaluated the ability of a custom dual-energy CT (DECT) post-processing material decomposition method to image bone marrow edema after acute knee injury. Using an independent validation cohort, the DECT method was compared to gold-standard, fluid-sensitive MRI. By including both quantitative voxel-by-voxel validation outcomes and semi-quantitative radiologist scoring-based assessment of diagnostic accuracy, we aimed to provide insight into the relationship between quantitative metrics and the clinical utility of imaging methods. MATERIALS AND METHODS: Images from 35 participants with acute anterior cruciate ligament injuries were analyzed. DECT material composition was applied to identify bone marrow edema, and the DECT result was quantitatively compared to gold-standard, registered fluid-sensitive MRI on a per-voxel basis. In addition, two blinded readers rated edema presence in both DECT and fluid-sensitive MR images for evaluation of diagnostic accuracy. RESULTS: Semi-quantitative assessment indicated sensitivity of 0.67 and 0.74 for the two readers, respectively, at the tibia and 0.55 and 0.57 at the femur, and specificity of 0.87 and 0.89 for the two readers at the tibia and 0.58 and 0.89 at the femur. Quantitative assessment of edema segmentation accuracy demonstrated mean dice coefficients of 0.40 and 0.16 at the tibia and femur, respectively. CONCLUSION: The custom post-processing-based DECT method showed similar diagnostic accuracy to a previous study that assessed edema associated with ligamentous knee injury using a CT manufacturer-provided, built-in edema imaging application. Quantitative outcome measures were more stringent than semi-quantitative scoring methods, accounting for the low mean dice coefficient scores.

Independent changes in bone mineralized and marrow soft tissues following acute knee injury require dual-energy or high-resolution computed tomography for accurate assessment of bone mineral density and stiffness.

Musculoskeletal injuries often induce local accumulation of blood and/or fluid within the bone marrow, which is detected on medical imaging as edema-like marrow signal intensities (EMSI). In addition to its biological effects on post-injury recovery, the displacement of low-attenuating, largely adipocytic marrow by EMSI may introduce errors into quantitative computed tomography (QCT) measurements of bone mineral density (vBMD) and resulting bone stiffness estimates from image-based finite element (FE) analysis. We aimed to investigate the impact of post-injury changes in marrow soft tissue composition on CT-based bone measurements by applying CT imaging at multiple spatial resolutions. To do so, dual energy QCT (DECT) material decomposition was used to detect EMSI in the tibiae of nineteen participants with a recent anterior cruciate ligament tear. We then measured bone density and FE-based apparent modulus within the EMSI region and in a matched volume in the uninjured contralateral knee. Three measurement methods were applied: 1.) standard, QCT density calibration and density-based FEM; 2.) a DECT density calibration that provides density measurements adjusted for marrow soft tissues; and 3.) high-resolution peripheral QCT (HR-pQCT) density and microFE analyses. When measured using standard, single-energy QCT, vBMD and apparent modulus were elevated in the EMSI compared to the contralateral. After adjusting for marrow soft tissue composition using DECT, these measurements were no longer different between the two regions. By allowing for high-resolution, localized density analysis, HR-pQCT indicated that trabecular tissue mineral density was 9 mgHA/cm3 lower, while density of marrow soft tissues was 18 mgHA/cm3 higher, in the EMSI than the contralateral region, suggesting that EMSI have opposite effects on the measured density of trabecular bone and the underlying soft marrow. Thus, after an acute injury, altered composition of marrow soft tissues may artificially inflate overall measurements of bone density and apparent modulus obtained using standard QCT. This can be corrected by accounting for marrow soft tissue attenuation, either by using DECT-based density calibration or HR-pQCT microFE and measurements of local density of trabeculae.

Health-Related Outcomes 3-15 Years Following Ankle Sprain Injury in Youth Sport: What Does the Future Hold?

BACKGROUND: This study examined the association between youth sport-related ankle sprain injury and health-related outcomes, 3-15 years postinjury. METHODS: A historical cohort study in which uninjured controls were cluster-matched with injured cases. The primary outcome was self-reported Foot and Ankle Outcome Score (FAOS). Secondary outcomes included measures of adiposity, validated questionnaires for physical activity, athletic identity, fear of pain, and tests of strength, balance, and function. RESULTS: We recruited 86 participants (median age of 23 years; 77% female); 50 with a time-loss ankle sprain, median of 8 years postinjury, and 36 uninjured controls cluster-matched by sex and sport. Based on mixed effects multivariable regression models, previously injured participants demonstrated poorer outcomes than controls on all 5 FAOS subscales regardless of sex and time since injury, with the largest differences observed in symptoms (-20.9, 99% CI: -29.5 to -12.3) and ankle-related quality of life (-25.3, 99% CI: -34.7 to -15.9) subscales. Injured participants also had poorer unipedal dynamic balance (-1.9, 99% CI: 3.5 to -0.2) and greater fear of pain (7.2, 99% CI: 0.9-13.4) compared with controls. No statistically significant differences were found for other secondary outcomes. CONCLUSION: At 3-15 years following time-loss ankle sprain injury in youth sport, previously injured participants had more pain and symptoms, poorer self-reported function, ankle-related quality of life, reduced sport participation, balance, and greater fear of pain than controls. This underlines the need to promote the primary prevention of ankle sprains and secondary prevention of potential health consequences, including posttraumatic osteoarthritis. LEVEL OF EVIDENCE: Level III, historical cohort study.

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.

Locomotory behaviour of early tetrapods from Blue Beach, Nova Scotia, revealed by novel microanatomical analysis.

Evidence for terrestriality in early tetrapods is fundamentally contradictory. Fossil trackways attributed to early terrestrial tetrapods long predate the first body fossils from the Late Devonian. However, the Devonian body fossils demonstrate an obligatorily aquatic lifestyle. Complicating our understanding of the transition from water to land is a pronounced gap in the fossil record between the aquatic Devonian taxa and presumably terrestrial tetrapods from the later Early Carboniferous. Recent work suggests that an obligatorily aquatic habit persists much higher in the tetrapod tree than previously recognized. Here, we present independent microanatomical data of locomotor capability from the earliest Carboniferous of Blue Beach, Nova Scotia. The site preserves limb bones from taxa representative of Late Devonian to mid-Carboniferous faunas as well as a rich trackway record. Given that bone remodels in response to functional stresses including gravity and ground reaction forces, we analysed both the midshaft compactness profiles and trabecular anisotropy, the latter using a new whole bone approach. Our findings suggest that early tetrapods retained an aquatic lifestyle despite varied limb morphologies, prior to their emergence onto land. These results suggest that trackways attributed to early tetrapods be closely scrutinized for additional information regarding their creation conditions, and demand an expansion of sampling to better identify the first terrestrial tetrapods.

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.

Reliability and Change in Erosion Measurements by High-resolution Peripheral Quantitative Computed Tomography in a Longitudinal Dataset of Rheumatoid Arthritis Patients.

OBJECTIVE: The aim of this multireader exercise was to assess the reliability and change over time of erosion measurements in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: HR-pQCT scans of 23 patients with RA were assessed at baseline and 12 months. Four experienced readers examined the dorsal, palmar, radial, and ulnar surfaces of the metacarpal head (MH) and phalangeal base (PB) of the second and third digits, blinded to time order. In total, 368 surfaces (23 patients´ 16 surfaces) were evaluated per timepoint to characterize cortical breaks as pathological (erosion) or physiological, and to quantify erosion width and depth. Reliability was evaluated by intraclass correlation coefficients (ICC), percentage agreement, and Light k; change over time was defined by means ± SD of erosion numbers and dimensions. RESULTS: ICC for the mean measurements of width and depth of the pathological breaks ranged between 0.819-0.883, and 0.771-0.907, respectively. Most physiological cortical breaks were found at the palmar PB, whereas most pathological cortical breaks were located at the radial MH. There was a significant increase in both the numbers and the dimensions of erosions between baseline and follow-up (P = 0.0001 for erosion numbers, width, and depth in axial plane; P = 0.001 for depth in perpendicular plane). CONCLUSION: This exercise confirmed good reliability of HR-pQCT erosion measurements and their ability to detect change over time.

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.

The utility of multi-stack alignment and 3D longitudinal image registration to assess bone remodeling in rheumatoid arthritis patients from second generation HR-pQCT scans.

BACKGROUND: Medical imaging plays an important role in determining the progression of joint damage in rheumatoid arthritis (RA). High resolution peripheral quantitative computed tomography (HR-pQCT) is a sensitive tool capable of evaluating bone microarchitecture and erosions, and 3D rigid image registration can be used to visualize and quantify bone remodeling over time. However, patient motion during image acquisition can cause a "stack shift" artifact resulting in loss of information and reducing the number of erosions that can be analyzed using HR-pQCT. The purpose of this study was to use image registration to improve the number of useable HR-pQCT scans and to apply image-based bone remodeling assessment to the metacarpophalangeal (MCP) joints of RA patients. METHODS: Ten participants with RA completed HR-pQCT scans of the 2nd and 3rd MCP joints at enrolment to the study and at a 6-month follow-up interval. At 6-months, an additional repeat scan was acquired to evaluate reliability. HR-pQCT images were acquired in three individual 1 cm acquisitions (stacks) with a 25% overlap. We completed analysis first using standard evaluation methods, and second with multi-stack registration. We assessed whether additional erosions could be evaluated after multi-stack registration. Bone remodeling analysis was completed using registration and transformation of baseline and follow-up images. We calculated the bone formation and resorption volume fractions with 6-month follow-up, and same-day repositioning as a negative control. RESULTS: 13/57 (23%) of erosions could not be analyzed from raw images due to a stack shift artifact. All erosions could be volumetrically assessed after multi-stack registration. We observed that there was a median bone formation fraction of 2.1% and resorption fraction of 3.8% in RA patients over the course of 6 months. In contrast to the same-day rescan negative control, we observed median bone formation and resorption fractions of 0%. CONCLUSIONS: Multi-stack image registration is a useful tool to improve the number of useable scans when analyzing erosions using HR-pQCT. Further, image registration can be used to longitudinally assess bone remodeling. These methods could be implemented in future studies to provide important pathophysiological information on the progression of bone damage.