Objective Extrusion of the meniscus is known to be a key factor in the development of knee osteoarthritis. Here, we investigate the precise relationship between meniscal extrusion and weight bearing 3-D joint space width (JSW) distribution. Design Weight-bearing computed tomography (WBCT) images were acquired at the 144-month visit in the Multicenter Osteoarthritis Study. For each knee, 3-D JSW maps were created. MRI data from the same visit were assessed for both medial and lateral meniscal extrusion grade determined by the MRI Osteoarthritis Knee Score. Statistical parametric mapping (SPM) was used to test for any significant dependence of 3-D JSW distribution on meniscal extrusion grade by location. Results 568 knees were included in the analysis. SPM demonstrated significant differences in 3-D JSW distribution according to the extent of both medial and anterior extrusion of the medial meniscus in a pattern that suggested a posteromedial shift of the femur on the tibia. Medial extrusion of the medial meniscus was also associated with significantly lower JSW across the central-to-posterior medial joint space. The low prevalence of lateral meniscus extrusion meant that results for this may be underpowered or unrepresentative. Conclusion Establishing links between 3-D JSW and meniscal extrusion is an important step in developing the clinical utility of WBCT for the evaluation of osteoarthritis. Further study is required to establish whether 3-D JSW is sensitive enough to detect meniscal extrusion before articular cartilage damage has occurred, to develop this as a biomarker for early disease.

Purpose: 3-D joint space width (JSW) measured from weight bearing CT (WBCT) has been suggested to be more sensitive than radiographic 2-D measurement in detecting joint space narrowing (JSN), but its diagnostic value in osteoarthritis is yet to be established. The purpose of this study was to determine the predictive validity of 3-D JSW measurement from baseline WBCT compared to 2-D radiographic measures in identifying structural disease progression at the knee.

Joint alignment is an important factor in OA affecting how forces pass through the knee. The increasing use of weight bearing computed tomography (WBCT) in OA research has made the weight bearing stance an important consideration in 3-D imaging analysis, but its influence through biomechanics on the joint and subchondral bone is not fully understood. To investigate the relationship between knee joint alignment and 3-D joint parameters derived from joint space mapping of WBCT imaging in individuals with radiographic OA. WBCT of both knees was acquired at the 144-month visit of the Multicenter Osteoarthritis Study (MOST). Knees with a KLG ≥2 were included in the analysis, taking the side with higher KLG or averaging subsequent results from both sides if equal. Joint space mapping was performed to obtain the 3-D JSW distribution along with femoral (f) and tibial (t) subchondral bone thickness (ST) and trabecular attenuation (TA). Everyone's knee parameter maps were then transferred to a canonical joint surface. Alignment of the knee joint was measured as the angle between the central axis of the distal femur and proximal tibia in a coronal multiplanar reformat slab of the WBCT data: neutral alignment was set as zero with varus signed positive (figure part (a)). Statistical parametric mapping (SPM) was performed using a general linear model to test the dependence of each 3-D parameter distribution on alignment controlling for age, sex, mass, height, and joint space shape modes. SPM results were plotted on the canonical joint surface with unmasked regions representing a significance level of P<0.05. 136 knees were included in the analysis, 84 of which were females. Mean ± SD age was 66.4 ± 9.8 yrs; mass 85.3 ± 17.8 kg; height 1.69 ± 0.1 m. The distribution of radiographic grading was KL2 = 103; KL3 = 32; KL4 = 1. Mean alignment was 0.38 ± 3.80°. For each degree from valgus to varus, JSW was significantly narrower in the medial compartment and wider in the lateral compartment by up to 0.1 mm (figure part (d)). While TA was significantly greater by up to 10 AU in the medial femur (figure part (b)) and medial tibia (figure part (f)), there was up to 0.05 mm significantly thinner ST in the lateral femur (figure part (c)) and lateral tibia (figure part (e)). The opposite effects can be inferred for each degree towards valgus. The same analysis on KLG 0 and 1 knees in the same cohort (mean ± SD alignment 0.66 ± 2.94°) revealed no significant relationships. Subchondral bone plate and trabecular bone appear to behave differently in the medial and lateral compartments when considering knee joint alignment in individuals with OA. Greater subchondral trabecular bone attenuation was seen in the medial compartment with varus alignment, while greater subchondral bone plate thickness was seen in the lateral compartment with valgus alignment. Whether alignment is the cause or effect of OA and any altered biomechanics that may influence bone and joint space behaviour requires further investigation, but this study does establish that the forces associated with alignment appear to have different effects on subchondral bone in different compartments. National Institutes of Health, University of Kansas (R01AR071648), University of Iowa (U01AG18832) and University of California-San Francisco (U01AG19069). NS is a consultant for Integra BioLife, Trice Medical and Pacira Biosciences. TT has been a consultant for Curvebeam AI. The authors would like to thank participants and staff of the MOST study. CORRESPONDENCE ADDRESS: [email protected]

We present a 3-D approach to joint space width (JSW) measurement across the ankle from weight-bearing CT (WBCT) to demonstrate inter-operator reproducibility, test-retest repeatability, and how differences in angulation affect ankle JSW distribution. One side from repeat WBCT imaging of both feet and ankles was analysed from 23 individuals as part of their routine clinical care pathway. Joint space mapping was performed at four facets across the talus: talonavicular, talar dome and medial gutter (dome-medial), lateral gutter, and posterior subtalar. Inter-operator reproducibility was calculated for two users, while test-retest repeatability was calculated by comparing the two visits, both presented as Bland-Altman statistics. Statistical parametric mapping determined any significant relationships between talocrural joint space angulation and 3-D JSW distribution. The average ± standard deviation interval between imaging was 74.0 ± 29.6 days. Surface averaged bias ± limits of agreement were similar for reproducibility and repeatability, the latter being: talonavicular 0.01 ± 0.26 mm, dome-medial 0.00 ± 0.28 mm, lateral gutter − 0.02 ± 0.40 mm, and posterior subtalar 0.02 ± 0.34 mm. Results are presented as 3-D distribution maps, with optimum test–retest repeatability reaching a smallest detectable difference of ± 0.15 mm. Joint space mapping is a robust approach to 3-D quantification of JSW measurement, inter-operator reproducibility, and test–retest repeatability at the ankle, with sensitivity reaching a best value of ± 0.15 mm. Standardised imaging protocols and optimised metal artefact reduction will be needed to further understand the clinical value of these 3-D measures derived from WBCT. Weight-bearing computed tomography is an increasingly important tool in the clinical assessment of orthopaedic ankle disorders. This paper establishes the performance of measuring 3-D joint space width using this technology, which is an important surrogate marker for severity of osteoarthritis. • Joint space width values and error metrics from across the ankle measured from weight-bearing CT can be presented as 3-D maps that show topographic variation. • The best sensitivity for detecting meaningful change in 3-D joint space width at the ankle was ± 0.15 mm, a value less than the isotropic imaging voxel dimensions. • Standardised imaging protocols and optimised metal artefact reduction will be needed to understand the clinical value of 3-D measures from weight-bearing CT.

Purpose: Weight bearing computed tomography (WBCT) has been increasingly used in the imaging of knee osteoarthritis in recent years because of its ability to assess the weight bearing joint space. However, relatively little is known regarding the extent to which this cone beam technology can provide useful information on peri-articular bone. The purpose of this study was to explore the relationships between quantitative WBCT-derived 3-D bone parameters at the distal femur with concurrent joint space narrowing phenotypes as a platform for developing new bone-based biomarkers in knee osteoarthritis.

(1) Background: During a cochlear implant insertion, the mechanical trauma can cause residual hearing loss in up to half of implantations. The forces on the cochlea during the insertion can lead to this mechanical trauma but can be highly variable between subjects which is thought to be due to differing anatomy, namely of the scala tympani. This study presents a systematic investigation of the influence of different geometrical parameters of the scala tympani on the cochlear implant insertion force. The influence of these parameters on the insertion forces were determined by testing the forces within 3D-printed, optically transparent models of the scala tympani with geometric alterations. (2) Methods: Three-dimensional segmentations of the cochlea were characterised using a custom MATLAB script which parametrised the scala tympani model, procedurally altered the key shape parameters (e.g., the volume, vertical trajectory, curvature, and cross-sectional area), and generated 3D printable models that were printed using a digital light processing 3D printer. The printed models were then attached to a custom insertion setup that measured the insertion forces on the cochlear implant and the scala tympani model during a controlled robotic insertion. (3) Results: It was determined that the insertion force is largely unaffected by the overall size, curvature, vertical trajectory, and cross-sectional area once the forces were normalised to an angular insertion depth. A Capstan-based model of the CI insertion forces was developed and matched well to the data acquired. (4) Conclusion: By using accurate 3D-printed models of the scala tympani with geometrical alterations, it was possible to demonstrate the insensitivity of the insertion forces to the size and shape of the scala tympani, after controlling for the angular insertion depth. This supports the Capstan model of the cochlear implant insertion force which predicts an exponential growth of the frictional force with an angular insertion depth. This concludes that the angular insertion depth, rather than the length of the CI inserted, should be the major consideration when evaluating the insertion force and associated mechanical trauma caused by cochlear implant insertion.

Weight bearing CT (WBCT) technology has been increasingly used in imaging of knee osteoarthritis in recent years because of its ability to assess the weight bearing joint space. However, relatively little is known regarding the extent to which this cone beam technology can provide useful information on peri-articular bone beyond the subchondral regions. To explore relationships between WBCT-derived 3-D cortical bone thickness and trabecular bone attenuation at the distal femur with concurrent joint space narrowing phenotypes. WBCT imaging was obtained ancillary to the Multicenter Osteoarthritis Study at the 144-month visit. After semi-automatic segmentation, femoral cortical thickness (fCT) and trabecular attenuation (fTA) maps were created for each of 663 available distal femurs using cortical bone mapping. A template was registered to each individual distal femur and a 3-D statistical shape model created, followed by transfer of fCT and fTA distribution maps onto the template. A statistical parametric mapping (SPM) general linear model adjusted for age, sex, BMI, and the first 5 shape modes (controlling for effects of systematic misregistration) was used to test the dependence of fCT and fTA in turn on the experimental variables of concurrent radiographic medial and lateral OARSI joint space narrowing (JSN) grade. One knee from each participant was selected for inclusion, taking the side with worse compartmental baseline JSN grade or randomly if equal. 16 knees were excluded due to unachievable registration, with a final study set of a single knee from 386 individuals. 219 were female, mean ± SD age was 63.6 ± 9.6 yrs, mass 82.3 ± 17.7 kg, height 169 ± 9 cm, and BMI 28.5 ± 5.0 kg/m2. SPM significance ROIs according to baseline medial (left, figs 1 & 2) and lateral (right, figs 3 & 4) JSN phenotypes are shown for fCT (top row, figs 1 & 3) and fTA (bottom row, figs 2 & 4). SPM revealed significantly greater fCT by up to ∼0.1mm and fTA by up to ∼40 attenuation units (AU) for each increment in baseline JSN grade along the outer margin of the respective compartments (unmasked blue zones in each figure). Significantly greater fCT by up to ∼0.1mm for each increment in medial JSN grade also spread across the anterior aspect of the medial femoral condyle suggesting a wider regional relationship. 3-D distribution of fCT and fTA follow distinct patterns according to OARSI JSN phenotype, relating to recognised distributions of marginal osteophytosis and subchondral sclerosis. These results indicate that cone beam WBCT can quantify cardinal bony structural features of osteoarthritis and that their distribution is related to specific osteoarthritis OARSI JSN phenotypes. National Institutes of Health, University of Kansas (R01AR071648), University of Iowa. (U01AG18832), University of California-San Francisco (U01AG19069), Boston University (U01AG018820). NS is a consultant for Integra BioLife, Trice Medical and Pacira Biosciences. The authors would like to thank participants and staff of the MOST study. CORRESPONDENCE ADDRESS: [email protected]

3-D joint space width (JSW) measured from weight bearing CT (WBCT) has been suggested to be more sensitive than radiographic 2-D measurement in detecting joint space narrowing (JSN), but its diagnostic value in osteoarthritis is yet to be established. To determine the predictive validity of 3-D JSW measurement from baseline WBCT compared to 2-D radiographic measures in identifying structural disease progression at the knee. WBCT knee imaging was acquired at the 144-month visit of the Multicenter Osteoarthritis Study (MOST) with radiographic Kellgren and Lawrence grade (KLG), medial and lateral tibiofemoral radiographic OARSI JSN grades. Progression in medial and lateral JSN grade was recorded 2 years subsequent. After semi-automatic segmentation of 663 available knees, joint space mapping was performed to create 3-D JSW maps. A template was registered to each individual joint surface, a 3-D statistical shape model created, and JSW measurements transferred to the template. A statistical parametric mapping (SPM) general linear model adjusted for age, sex, BMI, and the first 5 shape modes (controlling for effects of systematic misregistration) was used to test the dependence of baseline 3-D JSW on baseline medial and lateral JSN in turn. One knee per participant was included in the SPM model, when required selecting side according to worst baseline compartmental JSN grade or randomly if equal. Mean JSW values from significantly narrower SPM ROIs were taken for all knees and used in receiver operating characteristic analysis to deliver areas under the curve (AUC) in a leave-one-out cross-validation classifier predictive model for future worsening of medial and lateral JSN at 2 years. This prediction model also tested baseline KLG, medial and lateral JSN grade. All predictive models were controlled by inclusion of age, sex, and BMI and compared against each other. 10 knees did not have radiographic grading, so the study set consisted of 653 knees from 394 individuals. 218 participants were female, mean ± SD age was 63.5 ± 9.6 years, mass 82.7 ± 17.7 kg, height 170 ± 9 cm, and BMI 28. 5 ± 5.0 kg/m2. SPM revealed regions of significantly narrower baseline medial JSW up to ∼0.75 mm per increment in medial JSN grade (unmasked medial compartment red zone in fig. 1) and narrower baseline lateral JSW up to ∼1 mm per increment in baseline lateral JSN grade (unmasked lateral compartment red zone in fig. 2). Mean medial and lateral ROI JSW values were taken at all available knees for predictive modelling. AUC values with 95% confidence limits showed that baseline mean medial ROI JSW (0.68, 0.61-0.74) was worse than baseline KLG (0.75, 0.68-0.81) and no better than medial JSN (0.73, 0.65-0.79) or lateral JSN (0.66, 0.6-0.71) in predicting future medial JSN. However, baseline mean lateral ROI JSW (0.84, 0.72-0.91) was better than medial JSN (0.61, 0.49-0.72) and lateral JSN (0.71, 0.54-0.86) in prediction of future lateral JSN. It was also better than baseline KLG (0.77, 0.76-0.86) but not outside the 95% confidence limits, however combining baseline lateral ROI JSW and KLG in the model further improved the AUC (0.87, 0.78-0.92) beyond the limits for just KLG (0.77, 0.76-0.86). Baseline 3-D lateral compartment JSW from WBCT is better than 2-D radiographic measures at predicting progression in lateral compartment JSN, but the same was not seen for medial JSN. This suggests an important role for 3-D weight bearing JSW in assessment of knee osteoarthritis according to disease phenotype. National Institutes of Health, University of Kansas (R01AR071648), University of Iowa (U01AG18832) and University of California-San Francisco (U01AG19069). NS is a consultant for Integra BioLife, Trice Medical and Pacira Biosciences. The authors would like to thank participants and staff of the MOST study. CORRESPONDENCE ADDRESS: [email protected]

An important development in osteoarthritis imaging has been the ability to assess joint space width (JSW) from weight bearing CT (WBCT). The value of combining JSW with subchondral bone parameters in disease assessment is less well understood, particularly with respect to disease phenotype. To investigate associations of worsening medial and lateral tibiofemoral compartment structural disease over 2 years with a multivariate combination of baseline 3-D JSW and bony parameters from WBCT. WBCT knee imaging was acquired at the 144-month visit of the Multicenter Osteoarthritis Study along with same-visit and 2-year follow-up medial and lateral OARSI joint space narrowing (JSN) grade. After semi-automatic segmentation of 663 available knees, joint space mapping delivered 3-D JSW maps. Cortical bone mapping was performed to measure trabecular attenuation (TA), endocortical thickness (ET), and subchondral thickness (ST) at the femoral (f) and tibial (t) surfaces. A template was registered to each individual joint surface, a 3-D statistical shape model created, and all 7 spatially co-located parameters transferred to the template. A statistical parametric mapping (SPM) general linear model adjusted for age, sex, BMI, and the first 5 shape modes (controlling for effects of systematic misregistration) was used to test the dependence of JSW plus each bone parameter in turn on the experimental variables of 2-year medial and lateral OARSI JSN worsening. One knee per participant was used, selecting the side with greater JSN worsening, randomly if equal. 10 knees did not have radiographic grading, so the analysis used single knees from 394 individuals. 218 were female, mean ± SD age was 63.5 ± 9.6 years, mass 82.7 ± 17.7 kg, height 170 ± 9 cm, and BMI 28.5 ± 5.0 kg/m2. SPM results (figs 1-4 below) revealed significant parameter ROIs in the lateral tibiofemoral compartment that were associated with worsening of medial and lateral OARSI JSN grade at 2 years. Baseline lateral compartment JSW was significantly wider by up to ∼1 mm (unmasked lateral compartment blue zone in fig. 1) in combination with lower baseline tTA by up to ∼25 attenuation units (AU) (unmasked lateral compartment red zone in fig. 2) for each increment in future medial JSN over 2 years. The reverse was demonstrated for future lateral JSN with narrower baseline lateral JSW by up to ∼1 mm (unmasked lateral compartment red zone in fig. 3) in combination with higher baseline tTA by up to ∼25 AU (unmasked lateral compartment blue zone in fig. 4) for each grade of future lateral JSN over 2 years. Baseline JSW was significantly narrower at the lateral margin of the lateral compartment by up to ∼1 mm in combination with thicker tST and fST by up to ∼0.2 mm for each grade of future lateral JSN (not shown). Baseline medial 3-D JSW did not relate to any substantial significant future narrowing for any JSW-bone parameter combination for future medial or lateral JSN. ET results (with JSW) were very similar to those for ST at both sides of the joint. 3-D JSW analysed in combination with bone parameters at the lateral (but not medial) tibiofemoral compartment are significantly related to future medial and lateral OARSI JSN grade. Lower lateral compartment tTA (with higher JSW) is related to future medial JSN and may be an effect of trabecular remodelling from reduced lateral loading, while greater thickness of subchondral and endocortical bone in the lateral compartment (alongside lower JSW) can be explained by subchondral sclerosis. These results suggest the lateral compartment warrants closer attention for following both medial and lateral compartmental progression. National Institutes of Health, University of Kansas (R01AR071648), University of Iowa. (U01AG18832), University of California-San Francisco (U01AG19069), Boston University (U01AG018820). NS is a consultant for Integra BioLife, Trice Medical and Pacira Biosciences. The authors would like to thank participants and staff of the MOST study. CORRESPONDENCE ADDRESS: [email protected].

Objective:Computed tomography (CT) can deliver multiple parameters relevant to osteoarthritis. In this study we demonstrate that a 3-D multiparametric approach at the weight bearing knee with cone beam CT is feasible, can include multiple parameters from across the joint space, and can reveal stronger relationships with disease status in combination. Design:33 participants with knee weight bearing CT (WBCT) were analysed with joint space mapping and cortical bone mapping to deliver joint space width (JSW), subchondral bone plate thickness, endocortical thickness, and trabecular attenuation at both sides of the joint. All data were co-localised to the same canonical surface. Statistical parametric mapping (SPM) was applied in uni- and multivariate models to demonstrate significant dependence of parameters on Kellgren & Lawrence grade (KLG). Correlation between JSW and bony parameters and 2-week test-retest repeatability were also calculated. Results:SPM revealed that the central-to-posterior medial tibiofemoral joint space was significantly narrowed by up to 0.5 mm with significantly higher tibial trabecular attenuation up to 50 units for each increment in KLG as single features, and in a wider distribution when combined (p<0.05). These were also more strongly correlated with worsening KLG grade category. Test-retest repeatability was subvoxel (0.37 mm) for nearly all thickness parameters. Conclusions:3-D JSW and tibial trabecular attenuation are repeatable and significantly dependent on radiographic disease severity at the weight bearing knee joint not just alone, but more strongly in combination. A quantitative multiparametric approach with WBCT may have potential for more sensitive investigation of disease progression in osteoarthritis.

Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analyzed the data from a study collecting lumbar computed tomography (CT) spine scans at enrollment and 12 months post-treatment with romosozumab (210 mg sc monthly, n = 17), open-label daily teriparatide (20 mu g sc, n = 19), or placebo (sc monthly, n = 20). For each of the 56 women, cortical thickness (Ct.Th), endocortical thickness (Ec.Th), cortical bone mineral density (Ct.bone mineral density (BMD)), cancellous BMD (Cn.BMD), and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, color maps of the changes in the lumbar vertebrae structure were statistically analyzed and then visualized on the bone surface. At 12 months, romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral Ct.Th increase of 10.3% versus 4.3% for teriparatide, an Ec.Th increase of 137.6% versus 47.5% for teriparatide, a Ct.BMD increase of 2.1% versus a -0.1% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements, the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab-associated Cn.BMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared with the change in the placebo group (-4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture-prone areas of the vertebral shell, walls, and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. (c) 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

There is considerable interpersonal variation in the size and shape of the human cochlea, with evident consequences for cochlear implantation. The ability to characterize a specific cochlea, from preoperative computed tomography (CT) images, would allow the clinician to personalize the choice of electrode, surgical approach and postoperative programming. In this study, we present a fast, practicable and freely available method for estimating cochlear size and shape from clinical CT. The approach taken is to fit a template surface to the CT data, using either a statistical shape model or a locally affine deformation (LAD). After fitting, we measure cochlear size, duct length and a novel measure of basal turn non-planarity, which we suggest might correlate with the risk of insertion trauma. Gold-standard measurements from a convenience sample of 18 micro-CT scans are compared with the same quantities estimated from low-resolution, noisy, pseudo-clinical data synthesized from the same micro-CT scans. The best results were obtained using the LAD method, with an expected error of 8-17% of the gold-standard sample range for non-planarity, cochlear size and duct length.

Background Imaging of structural disease in osteoarthritis has traditionally relied on MRI and radiography. Joint space mapping (JSM) can be used to quantitatively map joint space width (JSW) in three dimensions from CT images. Purpose To demonstrate the reproducibility, repeatability, and feasibility of JSM of the knee using weight-bearing CT images. Materials and Methods Two convenience samples of weight-bearing CT images of left and right knees with radiographic Kellgren-Lawrence grades (KLGs) less than or equal to 2 were acquired from 2014 to 2018 and were analyzed retrospectively with JSM to deliver three-dimensional JSW maps. For reproducibility, images of three sets of knees were used for novice training, and then the JSM output was compared against an expert's assessment. JSM was also performed on 2-week follow-up images in the second cohort, yielding three-dimensional JSW difference maps for repeatability. Statistical parametric mapping was performed on all knee imaging data (KLG, 0-4) to show the feasibility of a surface-based analysis in three dimensions. Results Reproducibility (in 20 individuals; mean age, 58 years ± 7 [standard deviation]; mean body mass index, 28 kg/m2 ± 6; 14 women) and repeatability (in nine individuals; mean age, 53 years ± 6; mean body mass index, 26 kg/m2 ± 4; seven women) reached their lowest performance at a smallest detectable difference less than ±0.1 mm in the central medial tibiofemoral joint space for individuals without radiographically demonstrated disease. The average root mean square coefficient of variation was less than 5% across all groups. Statistical parametric mapping (33 individuals; mean age, 57 years ± 7; mean body mass index, 27 kg/m2 ± 6; 23 women) showed that the central-to-posterior medial joint space was significantly narrower by 0.5 mm for each incremental increase in the KLG (threshold P < .05). One knee (KLG, 2) demonstrated a baseline versus 24-month change in its three-dimensional JSW distribution that was beyond the smallest detectable difference across the lateral joint space. Conclusion Joint space mapping of the knee using weight-bearing CT images is feasible, demonstrating a relationship between the three-dimensional joint space width distribution and structural joint disease. It is reliably learned by novice users, can be personalized for disease phenotypes, and can be used to achieve a smallest detectable difference that is at least 50% smaller than that reported to be achieved at the highest performance level in radiography. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Roemer in this issue.

Purpose: Joint space mapping (JSM) is an image analysis tool that can measure, display, and set up for analysis of joint space width (JSW) distribution in 3D. It has been applied successfully at the hip and knee and is now demonstrated at the ankle using weight bearing cone beam computed tomography (CBCT). Our objective was to demonstrate: (1) feasibility of JSM at this site of complex anatomy in the presence of metalwork; (2) the effect of talocrural joint angulation on 3D JSW distribution; (3) JSM test-retest repeatability; and (4) JSM interoperator reproducibility. Methods: A convenience sample of 25 individuals with repeat weight bearing CBCT imaging of both feet and ankles performed within 4 months between 2013 and 2017 were retrospectively selected with no prior constraints on joint positioning. Imaging was acquired with a Curvebeam pedCAT scanner, 120 kVp, 0.37 mm isotropic voxels, FOV diameter 35 cm x height 20 cm, with a sharp reconstruction kernel. 2 individuals with metal-induced artefact were excluded because of failure of the JSM measurement algorithm. The mean ± sd age of the 23 study individuals was 52.7 ± 14.7 years, with 16 females and 7 males. Sides for analysis were selected to provide a mixture of pathology (13 left, 10 right). 11 ankles had no metalwork, 6 various metalwork fusions in the ipsilateral foot, 6 in the contralateral foot. The mean ± sd interval between imaging visits was 74.0 ± 29.6 days. JSM was performed by a single blinded operator at the medial talocrural (MTC, blue patch in first figure), lateral talocrural (LTC, purple), talonavicular (TN, red), and posterior subtalar (PST, orange) articular surfaces at both visits. A second operator trained on 6 opposite ankles, then performed JSM patch segmentation at each of the 23 baseline ankles. All results were registered to a set of average joint surfaces. Talocrural joint angulation was measured by a single blinded operator at each ankle from 3D reconstructions as the angle set by the lines connecting landmarks at the centre of the distal tibial diaphysis, the centre of the talar dome, and the centre of the talar head articular surface. The paired t-test was used to determine whether mean angle difference between visits significantly differed from 0°. Dependence of 3D JSW on angle difference and the null hypothesis of no difference in 3D JSW between visits were tested using statistical parametric mapping (SPM). Baseline and follow-up maps were used to show test-retest repeatability, while comparison of baseline maps was used to show interoperator reproducibility, both as Bland-Altman statistics. Results: Mean JSW values at visit 1 are shown in 3D on the average set of joint surfaces (second figure). The difference in angulation between visits was not significantly different from zero (2.7 ± 17.7°, p=0.30). SPM showed no significant dependence of difference between baseline and follow up 3D JSW on joint angulation nor any significant difference in 3D JSW difference from zero for between visits (threshold p<0.05). Global bias was 0.0 mm across all surfaces for test-retest repeatability and reproducibility. Repeatability limits of agreement at individual surfaces were: TN ±0.26 mm, MTC ±0.28 mm, ST ±0.34 mm, and LTC ±0.40 mm. Optimum sensitivity was less than ±0.2 mm at each central joint surface. Reproducibility limits of agreement at individual surfaces were: TN ±0.27 mm, MTC ±0.24 mm, ST ±0.31 mm, and LTC ±0.37 mm. 3D maps show the distribution of repeatability (third figure) and reproducibility (fourth figure) metrics across each joint surface.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conclusions: This is the first report of 3D surface-based measurement and analysis of JSW at this particular set of complex articular surfaces. JSM is feasible, reproducible, and sensitive in 3D JSW measurement from weight bearing CBCT to at least ±0.2mm across the ankle articular surfaces, which is subvoxel performance at nearly half of the isotropic voxel dimension. Uncontrolled angulation of the talocrural joint also appears not to be significantly different between baseline and follow-up imaging nor have any significant effect on 3D JSW distribution. Although there is a limit, if tolerated then JSM can still be performed in the presence of metalwork, which is a common feature for this particular patient population.

Purpose: Quantitative multiparametric analysis is usually only considered in the setting of magnetic resonance imaging. In this study we used multiparametric methods applied to cone beam computed tomography (CBCT) imaging to assess the knee joint during weight bearing, taking a surface-based approach to the measurement, display, and analysis of key 3D structures relevant to osteoarthritis. Methods: A convenience sample of 33 individuals with weight-bearing CBCT of both knees acquired between 2014 and 2018 and a full range of Kellgren and Lawrence grades (KLG) was used for this study. The mean ± SD age of participants at the time of imaging was 57.4 ± 7.2 years with 23 women and 10 men. The KLG breakdown for all 66 knees included in the analysis was KLG0 = 31, KLG1 = 12, KLG2 = 14, KLG3 = 7, and KLG4 = 2. All participants had both knees imaged simultaneously in a 20 degree fixed-flexion position with a CBCT imaging system. Imaging data were reconstructed with 0.37 mm isotropic voxels in a 200 x 350 mm axial field of view. All knees were analysed with joint space mapping (JSM) and cortical bone mapping (CBM). These techniques are able to measure joint space width (JSW) and bony parameters of trabecular density (TD), endocortical bone thickness (ET) and subchondral bone plate thickness (ST) in 3D at the distal femur (f) and proximal tibia (t) from a single CBCT acquisition. After registration of an average joint surface to each individual's surface, data can be analysed and presented on this average surface model. Horn's parallel analysis performed on the results of principal component analysis of the registration vectors showed that the first three shape modes were responsible for shape mode variation above background noise. In order to look at the dependence of each parameter on KLG with statistical parametric mapping (SPM), a general linear model was used with an experimental term of KLG and confounding terms of age, BMI, and these three shape modes to control for effects of systematic misregistration. Sex was not used in the model because of the correlation with the first shape mode (r = 0.80). Feature mean maps, correlation maps for bony parameters with JSW, and results of SPM for dependence of each parameter on KLG are displayed on the average surface model. An example of this model is shown here displaying mean JSW from across the study at the right knee superimposed on the grey distal femur (viewed from below). Results: Mean maps for each feature are displayed on the average model broken down by KLG<2, KLG=2, and KLG>2 categories. Bony parameters for the femur are presented here: Bony parameters for the tibia are presented here: JSW results are presented in the final figure alongside correlation results. SPM revealed that the central-to-posterior medial tibiofemoral joint space was significantly narrowed by up to 0.5 mm with significantly higher tTD by up to 50 attenuation units for each increment in KLG (p<0.05) both as single features (left) and together in multivariate analysis (right). A small patch at the medial aspect of the lateral tibiofemoral joint space also showed significance for JSW alone and JSW/tTD in combination (p<0.05). No other single features showed convincing significance with SPM, although there were similar but smaller patches of medial and lateral joint space significance for JSW in combination with tST and tET. Vertexwise correlation maps showed that JSW and tTD were more closely correlated with higher KLG category, with the percentage of joint space vertices correlating at r > |0.50| increasing from 2%, to 11%, to 30% for KLG<2, KLG=2, and KLG>2 respectively. Conclusions: These findings support that 3D JSW and tTD are significantly dependent on structural disease severity at the weight-bearing knee joint both alone and in combination. These parameters also show increased spatial correlation with worse radiological disease. Applying JSM and CBM techniques to much larger numbers of knees from the Multicenter Osteoarthritis Study to predict disease progression and patient-reported outcomes will advance knowledge regarding the clinical significance of these findings.

Osteoarthritis is an increasingly important health problem for which the main treatment remains joint replacement. Therapy developments have been hampered by a lack of biomarkers that can reliably predict disease, while 2D radiographs interpreted by human observers are still the gold standard for clinical trial imaging assessment. We propose a 3D approach using computed tomography-a fast, readily available clinical technique-that can be applied in the assessment of osteoarthritis using a new quantitative 3D analysis technique called joint space mapping (JSM). We demonstrate the application of JSM at the hip in 263 healthy older adults from the AGES-Reykjavík cohort, examining relationships between 3D joint space width, 3D joint shape, and future joint replacement. Using JSM, statistical shape modelling, and statistical parametric mapping, we show an 18% improvement in prediction of joint replacement using 3D metrics combined with radiographic Kellgren & Lawrence grade (AUC 0.86) over the existing 2D FDA-approved gold standard of minimum 2D joint space width (AUC 0.73). We also show that assessment of joint asymmetry can reveal significant differences between individuals destined for joint replacement versus controls at regions of the joint that are not captured by radiographs. This technique is immediately implementable with standard imaging technologies.

Purpose: To compare quantitative 3D joint analysis of computed tomography (CT) imaging data using joint space mapping (JSM) against current gold standard 2D radiographic criteria in a predictive model for future total hip replacement (THR). Methods: We undertook a nested case-control study within the prospective AGES-REYKJAVIK cohort of 3133 healthy older adults. Standard clinical CT of both hips was performed at study baseline with 1mm slice thickness. After initial 2:1 matching of THR cases for age and gender, exclusion criteria applied were THR for fracture rather than osteoarthritis (16 hips), movement artefact (6 hips), incomplete joint coverage (2 hips), and joint ankylosis (1 hip), leaving 80 case individuals with THR performed in the subsequent 5 years and 187 controls. There was no significant difference between the two groups in age (74.3 ± 4.7 vs 74.4 ± 4.9 yrs), sex (30:50 vs 69:118 male:female), nor BMI (27.9 ± 4.3 vs 27.5 ± 4.2 kg/m2). Kellgren and Lawrence (KL) grade and minimum 2D joint space width (JSW) were recorded for each hip from digitally reconstructed radiographs (Fig. 1). Joint space mapping was performed on CT imaging data from each hip to measure JSW in 3D between opposing joint surfaces. Resulting measurements presented on an average acetabular surface to which all individual surfaces were registered surface (Fig. 2). Statistical shape modelling used to determine shape modes. Horn’s parallel analysis showed that the first 16 shape modes were greater than noise in the principal component analysis coefficient matrix, the first 7 accounting for more than 90% of shape variation.Statistical parametric mapping (SPM) was performed on the 80 case THR and 187 control individuals to demonstrate significant regions of difference in 3D JSW between the two groups; paired hips were averaged to model the effect of coming from the same individual. The SPM generalised linear model included THR outcome, age, BMI, and the first 7 shape modes; sex highly correlated with shape mode 1 (scale) and was therefore removed from the model. ROC curves with AUC values were calculated using a leave-one-out cross-validation classifier predictive model for THR with hip pain (HP - any pain in the index hip for more than one month in the last year), KL grade, minimum 2D JSW (min2D), minimum 3D JSW within the SPM significance region of interest (ROI) divided by mean global JSW (min3D), and shape mode coefficients (SM). Results: SPM revealed a large area across the superior joint space in which JSW was dependent on future THR, significantly narrower in THR cases compared to controls by up to 1 mm (Fig. 3). This area was used as the ROI from which minimum 3D JSW was taken.Figure 4Shows the average shape of THR hips compared to non-THR controls.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Hip pain was the poorest predictor model (AUC = 0.69), while KL grade (0.72) and minimum 2D JSW (0.73) were outperformed by the first 7 shape modes (0.74) and minimum ROI 3D joint space width relative to the global mean (0.79). The AUC increased for the combination of 3D JSW and shape mode data (0.81), and was maximal when KL was also included (0.86) (Fig. 5). Conclusions: 3D joint space mapping of standard clinical CT imaging results in better prediction of future THR than current 2D radiographic gold standards in healthy older individuals. These results strongly advocate the use of JSM in clinical trials, with further exploration warranted into its clinical utility in stratification, monitoring, and prediction of joint diseases such as osteoarthritis.

Purpose: To demonstrate the feasibility of quantitative 3D joint space mapping (JSM) at the knee in a sample of standing computed tomography (CT) imaging from the Multicenter Osteoarthritis (MOST) Study . Methods: A convenience sample of 23 standing knee CT data sets covering both knees from MOST participants was sourced to include the full range of Kellgren and Lawrence (KL) grades. This had a mean age of 59.4 ± 6.8 yrs, BMI of 27.3 ± 6.1 kg/m2, and a female:male count of 16:7. A prototype of a commercial CT scanner (LineUp, CurveBeam, Warrington, PA) was used to acquire bilateral, weight-bearing images of both knees in a fixed-flexed stance. 3D datasets (isotropic voxels 0.37mm; field of view 350mm) were reconstructed from cone beam projections. JSM was performed on imaging data at each knee to measure JSW in 3D at the medial and lateral tibiofemoral compartments using a hybrid full-width-half-maximum (FWHM)-threshold technique on patches cut from the distal femur (Fig. 1). Femoral and tibial joint surface location and JSW (the distance between the two) were defined by the JSM measurement algorithm; we chose ‘halfway’ between the two surfaces as the surface representation of the whole 3D joint space (Fig. 2). Each of the ‘halfway’ joint space patches were registered to a canonical (average) surface created from both knees from all individuals (Fig. 3), with JSW data mapped onto these for presentation of mean and standard deviation (SD) JSW data and performing statistical analysis. An index knee side with the worse KL grade was selected from each individual, or randomly if equal, resulting in 23 single knees for analysis (Table 1). Statistical parametric mapping (SPM) was performed on these to look for any dependence of 3D JSW on KL grade, age, sex, and BMI. The same strategy was used to select index knees according to WOMAC pain score from the day of imaging, again using SPM to demonstrate any dependence of 3D JSW on pain (Table 1).Tabled 1KL grades and WOMAC pain scores for index knees in the respective SPM analyses.Score0123456789N for KL grade135221-----N for WOMACpain score10521310001 Open table in a new tab Results: Mean and SD of 3D JSW from all 46 sample knees are presented on the canonical patches (Fig. 4). SPM demonstrated that for each increase in KL grade (assuming linearity), there was a significant reduction in JSW of up to 0.75 mm at the medial compartment (statistically significant at P<0.05), and a non-significant trend for an increase in JSW up to 0.5 mm at the lateral tibiofemoral compartment (P>0.05). These results are presented alongside the mean JSW for the 18 knees with a KL grade <2 versus the 18 with a KL grade ≥2 (Fig. 5). There was no significance for dependence of 3D JSW on sex, BMI, age, or pain score, but there was a trend for joint space to be wider across both compartments in males compared to females. Conclusions: JSM is feasible at the knee using fixed positioning standing CT data from a cone beam acquisition, with the first such analysis in 3D showing that significant results can be achieved when related to the current 2D radiographic gold standard of KL grading. Further study is currently being undertaken to establish the reliability and sensitivity of JSM at the knee joint. We propose that JSM should then be applied in a larger cohort with known clinical outcome measures such as joint replacement and pain and with follow-up imaging in order to test predictive ability against current gold standard. This will help determine the suitability of JSM at the knee for use in clinical trials and the clinic setting.