A. Scharmga

Definition for Rheumatoid Arthritis Erosions Imaged with High Resolution Peripheral Quantitative Computed Tomography and Interreader Reliability for Detection and Measurement

Objective. High-resolution peripheral quantitative computed tomography (HR-pQCT) sensitively detects erosions in rheumatoid arthritis (RA); however, nonpathological cortical bone disruptions are potentially misclassified as erosive. Our objectives were to set and test a definition for pathologic cortical bone disruptions in RA and to standardize reference landmarks for measuring erosion size. Methods. HR-pQCT images of metacarpophalangeal joints of RA and control subjects were used in an iterative process to achieve consensus on the definition and reference landmarks. Independent readers (n = 11) applied the definition to score 58 joints and measure pathologic erosions in 2 perpendicular multiplanar reformations for their maximum width and depth. Interreader reliability for erosion detection and variability in measurements between readers [root mean square coefficient of variation (RMSCV), intraclass correlation (ICC)] were calculated. Results. Pathologic erosions were defined as cortical breaks extending over a minimum of 2 consecutive slices in perpendicular planes, with underlying trabecular bone loss and a nonlinear shape. Interreader agreement for classifying pathologic erosions was 90.2%, whereas variability for width and depth erosion assessment was observed (RMSCV perpendicular width 12.3%, axial width 20.6%, perpendicular depth 24.0%, axial depth 22.2%; ICC perpendicular width 0.206, axial width 0.665, axial depth 0.871, perpendicular depth 0.783). Mean erosion width was 1.84 mm (range 0.16–8.90) and mean depth was 1.86 mm (range 0.30–8.00). Conclusion. We propose a new definition for erosions visualized with HR-pQCT imaging. Interreader reliability for erosion detection is good, but further refinement of selection of landmarks for erosion size measurement, or automated volumetric methods, will be pursued.

Heterogeneity of Cortical Breaks in Hand Joints of Patients with Rheumatoid Arthritis and Healthy Controls Imaged by High-resolution Peripheral Quantitative Computed Tomography

Objective. Conventional radiographs (CR) of the hands are the gold standard for imaging bone erosions. The presence of bone erosions, reflected by the presence of cortical breaks, is a poor prognostic factor in patients with rheumatoid arthritis (RA). The availability of high-resolution peripheral quantitative computed tomography (HR-pQCT) enables detailed investigation of cortical breaks in rheumatic diseases. The aim of this image review is to show HR-pQCT images of the spectrum of cortical breaks with and without underlying trabecular bone changes in metacarpophalangeal (MCP) joints of healthy controls (HC) and patients with RA, with corresponding images on CR and magnetic resonance imaging (MRI). Methods. Second and third MCP joints of 41 patients (of which 10 were early RA with ≤ 2 years and 24 longstanding RA with ≥ 10 years of disease duration) and 38 HC were imaged by CR, MRI, and HR-pQCT (XtremeCT1, Scanco Medical AG). Representative images of the spectrum of cortical breaks were selected. Results. Cortical breaks were found in early and longstanding RA, but also in HC. They were heterogeneous in size, location, and number per joint, with a variety of surrounding cortical and underlying trabecular bone characteristics. Conclusion. Using HR-pQCT images of MCP joints, heterogeneous cortical breaks with and without surrounding trabecular bone changes were found, not only in RA but also in HC. The underlying mechanisms and significance of this spectrum of cortical breaks as found with high 3-D resolution needs further investigation.

An automated algorithm for the detection of cortical interruptions on high resolution peripheral quantitative computed tomography images of finger joints

Objectives To introduce a fully-automated algorithm for the detection of small cortical interruptions (≥0.246mm in diameter) on high resolution peripheral quantitative computed tomography (HR-pQCT) images, and to investigate the additional value of manual correction of the automatically obtained contours (semi-automated procedure). Methods Ten metacarpophalangeal joints from seven patients with rheumatoid arthritis (RA) and three healthy controls were imaged with HR-pQCT. The images were evaluated by an algorithm according to the fully- and semi-automated procedure for the number and surface of interruptions per joint. Reliability between the fully- and semi-automated procedure and between two independent operators was tested using intra-class correlation coefficient (ICC) and the proportion of matching interruptions. Validity of single interruptions detected was tested by comparing it to visual scoring, as gold standard. The positive predictive value (PPV) and sensitivity were calculated. Results The median number of interruptions per joint was 14 (range 2 to 59) and did not significantly differ between the fully- and semi-automated procedure (p = 0.37). The median interruption surface per joint was significantly higher with the fully- vs. semi-automated procedure (respectively, 8.6mm2 vs. 5.8mm2 and 6.1mm2, p = 0.01). Reliability was almost perfect between the fully- and semi-automated procedure for both the number and surface of interruptions (ICC≥0.95) and the proportion of matching interruptions was high (≥76%). Also the inter-operator reliability was almost perfect (ICC≥0.97, proportion of matching interruptions 92%). The PPV ranged from 27.6% to 29.9%, and sensitivity from 69.7% to 76.3%. Most interruptions detected with the algorithm, did show an interruption on a 2D grayscale image. However, this interruption did not meet the criteria of an interruption with visual scoring. Conclusion The algorithm for HR-pQCT images detects cortical interruptions, and its interruption surface. Reliability and validity was comparable for the fully- and semi-automated procedures. However, we advise the use of the semi-automated procedure to assure quality. The algorithm is a promising tool for a sensitive and objective assessment of cortical interruptions in finger joints assessed by HR-pQCT.

SAT0165 Cortical Breaks and Bone Erosions in the Hand Joints: A Cadaver Study Comparing Conventional Radiography with High-Resolution and Micro-Computed Tomography

Background Conventional radiography (CR) is considered the gold standard for diagnosing bone erosions in rheumatic diseases. However, High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) and microCT (μCT) allow analysis of bone erosions in finger joints at micro level. Objectives To evaluate cortical breaks and erosions in 16 hand joints imaged by CR, HR-pQCT and μCT. Methods Eight female human cadaveric index fingers with unknown medical history were scanned by HR-pQCT (82 μm, XtremeCT, Scanco Medical AG, Switzerland) and μCT (18μm, μCT 80, Scanco Medical AG, Switzerland). Also radiographs were taken. A modified SPECTRA (Study grouP for xtrEme Computed Tomography in Rheumatoid Arthritis) algorithm was used by one reader to assess all cortical breaks and all erosions. A cortical break was defined as an interruption of cortical bone on two consecutive slices on two orthogonal planes on HR-pQCT, and similarly, but on eight consecutive slices, for the μCT. Erosion was defined as a definite cortical break, with irregular shape, and loss of underlying trabecular bone on two consecutive slices on two orthogonal planes for HR-pQCT, and eight consecutive slices on two orthogonal planes for μCT. CRs were independently scored for erosions by two rheumatologists. Descriptives and intraclass correlation coefficients (ICC) were calculated. Results In total, eight metacarpal phalangeal (MCP), four proximal interphalangeal (PIP) and four distal interphalangeal joints of 16 cadaveric index fingers (mean ± SD age 82.6±9.1 years) were imaged by HR-pQCT and μCT. In total, 123 cortical breaks were detected on HR-pQCT (7.0±2.7 per joint) and 237 on μCT (14.5±5.0 per joint). A total of 24 erosions were detected on HR-pQCT (1.3±1.0 per joint) and 72 on μCT (4.0±2.6 per joint). The ICC for total number of cortical breaks was 0.399 (p=0.056), and for number of erosions -0.142 (p=0.706). On CR, twelve joints, eight MCPs and four PIPs, were scored. The total number of erosions scored on CR was four by Reader 1, and two by Reader 2. On the same joints, 16 and 45 erosions were scored on HR-pQCT and μCT, respectively. Conclusions HR-pQCT detected four times more erosions than CR. The μCT detected even three times more erosions than HR-pQCT. Furthermore, almost twice the number of cortical breaks was scored on μCT than HR-pQCT. These results indicate that further research, such as histological and longitudinal studies, will be necessary to reveal the prevalence, incidence and significance of cortical breaks and erosions as found by HR-pQCT and μCT of hand joints. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1851

Structural damage and inflammation on radiographs or magnetic resonance imaging are associated with cortical interruptions on high-resolution peripheral quantitative computed tomography: a study in finger joints of patients with rheumatoid arthritis and healthy subjects.

Objectives: To study the relationship between structural damage and inflammatory features on magnetic resonance imaging (MRI) or radiography and other risk factors [anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) seropositivity, hand dominance, disease duration] and the presence or number of cortical interruptions in finger joints on high-resolution peripheral quantitative computed tomography (HR-pQCT). Method: Finger joints of 38 healthy subjects and 39 patients with rheumatoid arthritis (RA) were examined through radiographs, MRI, and HR-pQCT. Radiographs were scored according to the Sharp/van der Heijde (SvH) method; MRI for the presence of cortical interruptions, bone marrow oedema (BMO), and synovitis; and HR-pQCT images for cortical interruptions. Descriptive statistics were calculated and associations examined using generalized estimating equations. Results: Cortical interruptions were found in healthy subjects and patients with RA on HR-pQCT (mean ± sd 0.33 ± 0.63 vs 0.38 ± 0.64 per joint quadrant, respectively, p < 0.01). Structural damage on MRI (cortical interruptions) or radiographs (SvH ≥ 1) was associated with the presence of cortical interruptions on HR-pQCT [odds ratio (OR) 12.4, 95% confidence interval (CI) 7.5–21.4, p < 0.01 and OR 4.8, 95% CI 1.9–11.7, respectively, p < 0.01]. The presence of BMO or synovitis was associated with more cortical interruptions on HR-pQCT (β 0.47, 95% CI 0.4–0.6, p < 0.01 and β 1.9, 95% CI 0.6–3.1, p < 0.01). In patients with RA, ACPA, and/or RF seropositivity, hand dominance and disease duration were not associated with more cortical interruptions on HR-pQCT. Conclusion: Structural damage and inflammatory features on MRI and radiographs are associated with cortical interruptions on HR-pQCT. No association between other risk factors and cortical interruptions was demonstrated.

Development of a scoring method to visually score cortical interruptions on high-resolution peripheral quantitative computed tomography in rheumatoid arthritis and healthy controls

Objectives To develop a scoring method to visually score cortical interruptions in finger joints on High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), determine its intra- and inter-reader reliability and test its feasibility. Methods The scoring method was developed by integrating results from in-depth discussions with experts, consensus meetings, multiple reading experiments and the literature. Cortical interruptions were scored by two independent readers in an imaging dataset with finger joints from patients with rheumatoid arthritis (RA) and healthy controls and assessed for adjacent trabecular distortion. Reliability for the total number of cortical interruptions per joint and per quadrant was calculated using intraclass correlation coefficient (ICC). Feasibility was tested by recording the time to analyze one joint. Results In 98 joints we identified 252 cortical interruptions, 17% had trabecular distortion. Mean diameter of the interruptions was significantly larger in patients with RA compared with healthy controls (0.88 vs 0.47 mm, p = 0.03). Intra-reader reliability was ICC 0.88 (95% CI 0.83;0.92) per joint and ICC 0.69 (95% CI 0.65;0.73) per quadrant. Inter-reader reliability was ICC 0.48 (95% CI 0.20;0.67) per joint and ICC 0.56 (95% CI 0.49;0.62) per quadrant. The time to score one joint was mean 9.2 (SD 4.9) min. Conclusions This scoring method allows detection of small cortical interruptions on HR-pQCT imaging of finger joints, which is promising for use in clinical studies.

Robotic (super) microsurgery: Feasibility of a new master-slave platform in an in vivo animal model and future directions: van Mulken et al.

Advanced microsurgical procedures are currently limited by human precision and manual dexterity. The potential of robotics in microsurgery is highlighted, including a general overview of applications of robotic assistance in microsurgery and its introduction in different surgical specialties. A new robotic platform especially designed for (super) microsurgery is presented. Results of an in vivo animal study underline its feasibility and encourage further development toward clinical studies. Future directions of robotic microsurgery are proposed.

Assessment of Cortical Interruptions in the Finger Joints of Patients With Rheumatoid Arthritis Using HR-pQCT, Radiography, and MRI: ASSESSMENT OF CORTICAL INTERRUPTIONS IN FINGER JOINTS OF PATIENTS WITH RA

Small cortical interruptions may be the first sign of an erosion, and more interruptions can be found in patients with rheumatoid arthritis (RA) compared with healthy subjects. First, we compared the number and size of interruptions in patients with RA with healthy subjects using high‐resolution peripheral quantitative CT (HR‐pQCT). Second, we investigated the association between structural damage and inflammatory markers on conventional radiography (CR) and MRI with interruptions on HR‐pQCT. Third, the added value of HR‐pQCT over CR and MRI was investigated. The finger joints of 39 patients with RA and 38 healthy subjects were examined through CR, MRI, and HR‐pQCT. CRs were scored using the Sharp/Van der Heijde method. MRI images were analyzed for the presence of erosions, bone marrow edema, and synovitis. HR‐pQCT images were analyzed for the number, surface area, and volume of interruptions using a semiautomated algorithm. Descriptives were calculated and associations were tested using generalized estimating equations. Significantly more interruptions and both a larger surface area and the volume of interruptions were detected in the metacarpophalangeal joints of patients with RA compared with healthy subjects (median, 2.0, 1.42 mm2, and 0.48 mm3 versus 1.0, 0.69 mm2, and 0.23 mm3, respectively; all p < 0.01). Findings on CR and MRI were significantly associated with more and larger interruptions on HR‐pQCT (prevalence ratios [PRs] ranging from 1.03 to 7.74; all p < 0.01) in all subjects, and were consistent in patients with RA alone. Having RA was significantly associated with more and larger interruptions on HR‐pQCT (PRs, 2.33 to 5.39; all p < 0.01), also after adjustment for findings on CR or MRI. More and larger cortical interruptions were found in the finger joints of patients with RA versus healthy subjects, also after adjustment for findings on CR or MRI, implying that HR‐pQCT imaging may be of value in addition to CR and MRI for the evaluation of structural damage in patients with RA.

FRI0662 Assessment of bone density, structure, and cortical interruptions of finger joints in patients with rheumatoid arthritis using high-resolution peripheral quantitative ct

Background Rheumatoid arthritis (RA) is characterized by peri-articular bone loss. In patients with RA, lower bone density and structural integrity, and an increased number of erosions compared to healthy controls (HCs) has been demonstrated using High-Resolution peripheral Quantitative CT (HR-pQCT) (1,2). To further characterize RA-related changes, we recently introduced a method for quantifying small cortical interruptions in finger joints (3). Objectives To investigate the cortical and trabecular bone density, structure, and cortical interruptions in MCP joints in early and late RA patients compared to HCs using HR-pQCT imaging. Methods The 2nd and 3rd MCP joint of 70 subjects (mean age 53.1 (SD 9.2) years) were evaluated by HR-pQCT (82μm isotropic voxel size): 38 HCs, 10 early RA (diagnosis ≤2 years ago) and 22 late RA (diagnosis ≥10 years ago). Images were analyzed for cortical interruptions, and for cortical and trabecular bone density and structure. Descriptives were analyzed per joint by one-way ANOVA with Bonferroni post-hoc testing or Kruskal-Wallis with Mann-Whitney post-hoc testing, as appropriate. Results Significant differences with respect to all parameters were found across the groups (Table 1). In early and late RA, the percentage of joints with at least 1 interruption was higher, and number of trabeculae, cortical thickness, total density and cortical density were lower than in HC. In addition, in late RA, number of interruptions, interruption volume and trabecular separation were higher, and trabecular density was lower than in HC. Bone loss at the cortical and trabecular bone was primarily observed at the rim of the joint (Figure 1, arrows).Table 1. Comparison of cortical interruptions, and bone density and structure parameters across early RA patients, late RA patients and HCs HC Early RA Late RA p-value Cortical interruption parameters n=82 n=39 n=73  Percentage of joints ≥1 interruption, % 69.5 89.7 * 82.2 0.025  Number of interruptions 1.50 (1.49) 2.64 (2.95) 5.22* (6.32) <0.001  Interruption volume, mm3 1.49 (5.16) 2.05 (6.76) 39.31* (78.51) <0.001 Bone density parameters n=50 n=31 n=68  Total vBMD, mg HA/cm3 327.3 (35.3) 295.8* (38.9) 286.4* (65.1) <0.001  Trabecular vBMD, mg HA/cm3 202.1 (20.6) 185.0 (21.6) 177.3* (42.0) <0.001  Cortical vBMD, mg HA/cm3 685.8 (42.8) 643.7* (58.2) 634.0* (73.3) <0.001 Bone structure parameters n=50 n=31 n=68  Trabecular number, mm1 1.68 (0.31) 1.45* (0.29) 1.52* (0.37) 0.004  Trabecular thickness, μm 102.3 (15.3) 109.1 (17.8) 98.6 (14.7) 0.009  Trabecular separation, μm 513.9 (116.9) 608.4 (132.3) 611.4* (220.6) 0.007  Distribution of trabecular separation, μm 550.6 (287.0) 728.5 (306.1) 689.4 (368.8) 0.029  Cortical thickness, μm 440.0 (99.2) 363.2* (90.2) 357.5* (132.8) <0.001 Values are displayed as mean (SD) or otherwise described. *Significantly different from HC, p<0.05. 1p-value obtained across the groups. vBMD, volumetric bone mineral density. Conclusions Bone density and structural integrity were impaired in early and late RA patients compared to HCs whereas the number of cortical interruptions is increased. The assessment of such parameters using HR-pQCT is, therefore, a promising tool for the follow-up of bone involvement in MCP joints in patients with RA. References Fouque-Aubert et al., ARD 2010. Stach et al., A&R 2010. Peters et al., ACR2016 (abstract). Disclosure of Interest M. Peters: None declared, A. Scharmga: None declared, A. van Tubergen: None declared, D. Loeffen: None declared, R. Weijers: None declared, B. van Rietbergen Consultant for: Scanco Medical AG, P. Geusens: None declared, J. van den Bergh: None declared

SAT0531 Can Histologically Defined Peri-Articular Vascular Channels Be Identified on High-Resolution Computed Tomography? A Study in Cadaveric Finger Joints

Background Several studies have indicated that High Resolution peripheral CT (HR-pQCT) scanning is more sensitive than radiography in detecting cortical breaks in destructive joint diseases like rheumatoid arthritis (RA)[1–3]. Cortical breaks are also seen in healthy controls, but the exact nature of these breaks is not known, and might represent vascular channels (VCs). No previous study has compared histology to HR-pQCT images in finger joints. We hypothesized that VCs seen on histology can also be detected by HR-pQCT imaging. Objectives To identify histologically defined VCs in cadaveric hand joints on HR-pQCT imaging. Methods Based on HR-pQCT, three regions in metacarpophalangeal joints from female cadavers with an unknown medical history (mean age 84.7, SD 5.5 years) were selected. These regions were extracted, embedded undecalcified in methylmetacrylate and histologically sectioned (thickness 15μm) parallel to the axial plane. Every second section (n=450) was stained with Goldner Trichrome. VCs were identified as a cortical break in one histological section which contained one or more vessels. HR-pQCT images (thickness 82μm) were independently scored by two trained readers for the presence of cortical breaks and if applicable categorized as VC. A break on HR-pQCT was defined as an interruption of the cortex seen on 2 consecutive slices in at least 2 orthogonal planes. A VC was defined as a break that is linear in shape with parallel lining. Finally, the histological sections were matched visually to corresponding axial HR-pQCT images. Results A total of 56 VCs were identified on histology. On HR-pQCT 20 breaks were identified, of which 7 were categorized as VC. Only 3 VCs matched with VCs on histology. Of the remaining 53 histologically identified VCs, 34 could be detected on HR-pQCT, but the interruption of the cortex was not seen on 2 consecutive slices therefore they were not classified as a break. Eight histologically VCs fulfilled the definition of a break on HR-pQCT, but were not categorized as a VC. Eleven histologically VCs could not be identified on HR-pQCT. Figure 1 demonstrates histology and HR-pQCT images. Conclusions VCs were frequently seen on histology. Only a minority of histologically defined VCs is interpreted as VC using a pre-specified definition on HR-pQCT images. Small histological VCs were often identified as an interruption but rarely considered a break according to the current definition of a VC on HR-pQCT. Therefore, additional criteria in order to diagnose the presence of VCs on HR-pQCT are warranted. References Stach CM, A&R.2010 Feb; 62(2):330–339. Srikhum W, JRheum.2013 Apr; 40(4):408–416. Fouque-Aubert A, ARD.2010 Sep; 69(9):1671–1676. Disclosure of Interest A. Scharmga: None declared, K. Keller: None declared, M. Peters: None declared, A. van Tubergen: None declared, J. van den Bergh: None declared, B. van Rietbergen Consultant for: Scanco Medical AG, R. Weijers: None declared, D. Loeffen: None declared, E. M. Hauge: None declared, P. Geusens: None declared