Erosive Progression by High-Resolution Peripheral Quantitative Computed Tomography and Conventional Radiography in Rheumatoid Arthritis.

OBJECTIVES: To investigate the diagnostic accuracy of high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess erosive progression during one year compared to conventional radiography (CR) in rheumatoid arthritis (RA). METHODS: This prospective study included 359 patients with RA (disease duration ≥ 5 years) between March 2018 and October 2020. HR-pQCT and CR were obtained at inclusion and after one year. Erosive assessment was performed at two metacarpophalangeal joints of the dominant hand using HR-pQCT and progression was defined as an increase in erosion number ≥ 1 or an increase in erosive volume > least significant change. CR of hands, wrists, and feet were evaluated using Sharp/van der Heijde scores and erosive progression was defined as a 1.1-point increase in erosion score according to the smallest detectable change. RESULTS: In paired analyses (n = 310), erosive progression was identified in 30 patients using CR and in 40 patients using HR-pQCT. In the 40 patients with erosive progression on HR-pQCT, progression was not identified by CR in 33 patients. Adding HR-pQCT to CR doubled the proportion of patients identified with progression from 30 (10%) to 63 (20%) patients. Using CR as the reference, the sensitivity (% (95% CI)) of HR-pQCT for identifying erosive progression was 23.3 (9.9-42.3) and the specificity was 88.2 (83.8-91.7). CONCLUSION: A substantial proportion of patients with erosive progression are overlooked using CR only to monitor erosive progression. Adding high-resolution peripheral CT to CR doubles the proportion of patients, who may benefit from individualised therapy targeting erosive progression in RA.

Investigating the Influence of Patient Eligibility Characteristics on the Number of Deferrable Rheumatologist Visits: Planning for a Patient-Initiated Follow-Up 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 having regularly scheduled follow-up. 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 7 rheumatologists' practices at 2 university-based clinics between March 1, 2021, and February 28, 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 4 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 patients with RA (71.5% female, 70% seropositive). Among all criteria sets, the proportion of visits that could be redirected varied between 2.5% and 20.9%. The highest proportion of deferrable visits was achieved when eligibility criteria included only stable disease activity and patients with RA on conventional synthetic disease-modifying antirheumatic 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.

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.

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.

Adapting the Intensity Gradient for Use with Count-Based Accelerometry Data in Children and Adolescents.

The intensity gradient is a new cutpoint-free metric that was developed to quantify physical activity (PA) measured using accelerometers. This metric was developed for use with the ENMO (Euclidean norm minus one) metric, derived from raw acceleration data, and has not been validated for use with count-based accelerometer data. In this study, we determined whether the intensity gradient could be reproduced using count-based accelerometer data. Twenty participants (aged 7-22 years) wore a GT1M, an ActiGraph (count-based), and a GT9X, ActiGraph (raw accelerations) accelerometer during both in-lab and at-home protocols. We found strong agreement between GT1M and GT9X counts during the combined in-lab activities (mean bias = 2 counts) and between minutes per day with different intensities of activity (e.g., sedentary, light, moderate, and vigorous) classified using cutpoints (mean bias < 5 min/d at all intensities). We generated bin sizes that could be used to generate IGs from the count data (mean bias = -0.15; 95% LOA [-0.65, 0.34]) compared with the original IG. Therefore, the intensity gradient could be used to analyze count data. The count-based intensity gradient metric will be valuable for re-analyzing historical datasets collected using older accelerometer models, such as the GT1M.

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.

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.

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.

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.

The Correction of Systematic Error due to Plaster and Fiberglass Casts on HR-pQCT Bone Parameters Measured In Vivo at the Distal Radius.

Due to difficulty assessing healing of distal radius fractures using conventional radiography, there is interest in using high resolution peripheral quantitative computed tomography (HR-pQCT) to track healing at the microarchitectural level. Unfortunately, the plaster-of-Paris and fiberglass casts used to immobilize fractures affect HR-pQCT measurements due to beam hardening, and increased noise. The challenge is compounded because casts have variable thickness, and an individual patient will often have their cast changed 2-3 times during the course of treatment. This study quantifies the effect of casts within a clinically relevant range of thicknesses on measured bone parameters at the distal radius, and establishes conversion equations to correct for systematic error in due to cast presence. Eighteen nonfractured participants were scanned by HR-pQCT in three conditions: no cast, plaster-of-Paris cast, and fiberglass cast. Measured parameters were compared between the baseline scan (no cast) and each cast scan to evaluate if systematic error exists due to cast presence. A linear regression model was used to determine an appropriate conversion for parameters that were found to have systematic error. Plaster-of-Paris casts had a greater range of thicknesses (3.2-9.5 mm) than the fiberglass casts (3.0-5.4 mm), and induced a greater magnitude of systematic error overall. Key parameters of interest were bone mineral density (total, cortical, and trabecular) and trabecular bone volume fraction, all of which were found to have systematic error due to presence of either cast type. Linear correlations between baseline and cast scans for these parameters were excellent (R2 > 0.98), and appropriate conversions could be determined within a margin of error less than a ±6% for the plaster-of-Paris cast, and ±4% for the fiberglass cast. We have demonstrated the effects of cast presence on bone microarchitecture measurements, and presented a method to correct for systematic error, in support of future use of HR-pQCT to study fracture healing.

Bilateral Asymmetry of Radius and Tibia Bone Macroarchitecture and Microarchitecture: A High-Resolution Peripheral Quantitative Computed Tomography Study.

Studies assessing bone health often select the dominant or nondominant limb to scan, but not both, for efficiency reasons. New scanning technology allows 3-dimensional (3D) visualization of the microarchitecture in bone, but it is not well understood whether there are differences between the dominant and nondominant limbs. Using 3D high-resolution peripheral quantitative computed tomography (HR-pQCT), the aim of this study is to investigate the effect of limb dominance on bone macroarchitecture and microarchitecture. Healthy male and female participants (N=100; 59 female, 41 male), mean age 30.7±12.1 years, were scanned at both radii and tibiae using HR-pQCT. Hand and foot dominance were determined by the participant's self-report. Most participants were right hand dominant (94.0%) and right foot dominant (91.0%). In the pooled cohort, the dominant radius had significantly greater cortical area (2.11%; p=0.002) and failure load (3.00%; p=0.001). At the tibia, the dominant foot had significantly lower bone mineral density (-0.77%; p=0.042), cortical area (-1.05%; p=0.031), and thickness (-1.51%; p=0.017). For females, there were no differences at the radius, but at the tibia, the dominant side had greater cross-sectional area (1.03%; p=0.044). Our data suggest that dominance has a small yet significant effect on macroarchitecture at both the ultradistal radius and tibia but not microarchitecture. This work emphasizes that it is important to be consistent in the selection of either dominant or nondominant limbs for HR-pQCT cohort studies; however, in the case where the opposite limb needs to be scanned, there would be small differences in macroarchitecture and no significant differences in microarchitecture anticipated.

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.

Assessment of the efficacy of MRI for detection of changes in bone morphology in a mouse model of bone injury.

PURPOSE: To determine whether magnetic resonance imaging (MRI) could be used to track changes in skeletal morphology during bone healing using high-resolution micro-computed tomography (µCT) as a standard. We used a mouse model of bone injury to compare µCT with MRI. MATERIALS AND METHODS: Surgery was performed to induce a burr hole fracture in the mouse tibia. A selection of biomaterials was immediately implanted into the fractures. First we optimized the imaging sequences by testing different MRI pulse sequences. Then changes in bone morphology over the course of fracture repair were assessed using in vivo MRI and µCT. Histology was performed to validate the imaging outcomes. RESULTS: The rapid acquisition with relaxation enhancement (RARE) sequence provided sufficient contrast between bone and the surrounding tissues to clearly reveal the fracture. It allowed detection of the fracture clearly 1 and 14 days postsurgery and revealed soft tissue changes that were not clear on µCT. In MRI and µCT the fracture was seen at day 1 and partial healing was detected at day 14. CONCLUSION: The RARE sequence was the most suitable for MRI bone imaging. It enabled the detection of hard and even soft tissue changes. These findings suggest that MRI could be an effective imaging modality for assessing changes in bone morphology and pathobiology.

Increasing the Number of Unloading/Reambulation Cycles does not Adversely Impact Body Composition and Lumbar Bone Mineral Density but Reduces Tissue Sensitivity.

A single exposure to hindlimb unloading leads to changes in body mass, body composition and bone, but the consequences of multiple exposures are not yet understood. Within a 18wk period, adult C57BL/6 male mice were exposed to one (1x-HLU), two (2x-HLU) or three (3x-HLU) cycles of 2 wk of hindlimb unloading (HLU) followed by 4 wk of reambulation (RA), or served as ambulatory age-matched controls. In vivo µCT longitudinally tracked changes in abdominal adipose and lean tissues, lumbar vertebral apparent volumetric bone mineral density (vBMD) and upper hindlimb muscle cross-sectional area before and after the final HLU and RA cycle. Significant decreases in total adipose tissue and vertebral vBMD were observed such that all unloaded animals reached similar values after the final unloading cycle. However, the magnitude of these losses diminished in mice undergoing their 2nd or 3rd HLU cycle. Irrespective of the number of HLU/RA cycles, total adipose tissue and vertebral vBMD recovered and were no different from age-matched controls after the final RA period. In contrast, upper hindlimb muscle cross-sectional area was significantly lower than controls in all unloaded groups after the final RA period. These results suggest that tissues in the abdominal region are more resilient to multiple bouts of unloading and more amenable to recovery during reambulation than the peripheral musculoskeletal system.

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.

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).

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.

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.