Mads Ammitzbøll-Danielsen

Aim: To evaluate the reliability and diagnostic performance of artificial intelligence (AI) driven robotic ultrasonography (RUS) compared with human ultrasonography (HUS) performed by a trained rheumatologist for assessing synovitis in the hands of healthy controls and patients with rheumatoid arthritis (RA). Methods: 20 healthy controls and 29 patients with RA eligible for initiation or intensification of disease-modifying anti-rheumatic drugs, with at least one clinically swollen joint in the hands, were included. The ultrasound robot scanned controls and patients twice without interval, whereas HUS was performed once. Synovitis was scored from 0 to 3 for Greyscale (GS) and Doppler (CD) by RUS (using AI software) and HUS according to the European League Against Rheumatism-OMERACT scoring system (range 0–66). Intrarobot and human-robot reliability and agreement were assessed. Furthermore, the diagnostic performance of RUS for detecting arthritis was evaluated using the clinical arthritis diagnosis as reference. Results: Intrarobot reliability was moderate to good, with intraclass correlation coefficients (ICCs) values of 0.65 (GS) and 0.86 (CD) in patients with RA. Human-robot agreement was moderate, with ICCs of 0.59 (GS) and 0.64 (CD). At joint level, RUS obtained higher scores for MCP joints than HUS, while scores were comparable for other joint groups. The diagnostic accuracy of RUS for detecting clinically-detected arthritis was 59%. Conclusion: A moderate to good overall agreement was seen between RUS and HUS in assessing synovitis in RA hands. However, at the joint level, low agreement was observed, particularly for MCP joints in both intrarobot and human-robot comparisons, which affected diagnostic performance.

The objective of this pilot study was to assess the impact of a salivary gland ultrasound (SGUS) atlas for scoring parenchymal changes in Sjögren’s syndrome by assessing the reliability of the scoring system (0–3), without and with the use of the SGUS atlas. Ten participants with varying experience in SGUS contributed to the reliability exercise. Thirty SGUS images of the submandibular and parotid gland with abnormalities ranging from 0 to 3 were scored using the written definitions of the OMERACT SGUS scoring system and using the SGUS atlas based on the OMERACT scoring system. For intra-reader reliability, two rounds were performed without and with the atlas—in the 2nd round the 30 images were rearranged in random order by a physician not included in the scoring. Inter-reader reliability was also determined in both rounds. Without using the atlas, the SGUS OMERACT scoring system showed fair inter-reader reliability in round 1 (mean kappa 0.36; range 0.06–0.69) and moderate intra-reader reliability (mean kappa 0.55; range 0.28–0.81). With the atlas, inter-reader reliability improved in round 1 to moderate (mean kappa 0.52; range 0.31–0.77) and intra-reader reliability to good (mean kappa 0.69; range 0.46–0.86). Higher intra-reader reliability was noted in participants with previous SGUS experience. The SGUS atlas increased both intra- and inter-reader reliability for scoring gland pathology in participants with varying SGUS experience suggesting a possible future role in clinical practice and trials. Key Points• Ultrasonography can detect parenchymal changes in salivary glands in patients with Sjögren’s disease.• An ultrasound atlas may improve reliability of scoring parenchymal changes in salivary glands.

Article: Optimizing the anti-inflammatory strategies in (osteo)arthritis - local or systemic? - The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2022 Jul 15 - Minerva Medica - Journals

The role of musculoskeletal ultrasound (MSUS) in routine care for diagnosing arthritis is not fully elucidated, but US is more sensitive than clinical joint examination for detecting synovitis. Therefore, the use of US may facilitate diagnosis of arthritis. The aim of the study was to assess if MSUS examination of hands and feet in relation to the first clinical visit had an impact on the time to reach a final diagnosis and the number of clinical follow-up visits needed after first consultation. Two cohorts referred to the outpatient arthritis clinic with suspected arthritis were compared with each other, 1. MSUS (October 2017 to June 2018) of hands and feet performed prior to the first clinical visit and 2. MSUS (November 2016 to June 2017) was performed Ad hoc, for following aspects: time to clinical diagnosis, number of clinical visits needed, and number of ultrasound examinations. In total, 163 and 109 patients were included in the MSUS and comparative cohorts, respectively. Adding MSUS to the first clinical visit reduced the time to diagnosis from mean 31(SD ± 32.2) days to 12(±17.3) days(p< 0.01). The number of clinical visits needed was reduced from mean 2.8(±1.1)–2.1(±1.3),(p< 0.01) corresponding to a reduction of 114 visits in the MSUS cohort. A final diagnosis with inflammatory arthritis was found in 76(47%) of patients in the MSUS cohort vs 29(27%) in the comparative cohort(p< 0.01). In patients referred for suspected arthritis, routine MSUS in relation to the first clinical visit significantly reduces time to diagnosis and number of clinical visits needed to reach a final diagnosis.

The novel technique of fluorescence optical imaging (FOI, Xiralite), which is approved in the European Union and the USA for clinical use, has been the object of studies since 2009. Indocyanine green-based FOI can demonstrate an impaired microcirculation caused by inflammation in both hands in one examination. Several studies have investigated FOI for detection of joint inflammation by comparing FOI to magnetic resonance imaging (MRI) and/or musculoskeletal ultrasound (MSUS). The results have shown a generally good agreement (>80%) between FOI and clinical examination, MRI and MSUS by power Doppler in inflammatory joint diseases. Moreover, characteristic enhancements in skin and nails are seen in PsA, which potentially can be useful in the diagnostic process of early undifferentiated arthritis. Furthermore, FOI has been investigated for the visualisation of a disturbed microcirculation in the hands and fingers of patients with systemic sclerosis (SSc), highlighting the potential of monitoring vascular changes in SSc and other vasculopathies. The available data indicate that it is time to consider FOI as a useful part of the imaging repertoire in rheumatology clinical practice, particularly where MSUS and MRI are not easily available.

Objectives: To develop and validate a new semiquantitative fluorescence optical imaging (FOI) scoring system—the FOI Enhancement-Generated RA Score (FOIE-GRAS) for synovitis assessment in the hand. Methods: The development of FOIE-GRAS was based on consensus of four experts in musculoskeletal imaging. Forty-six RA patients, eligible for treatment intensification and with ≥1 clinically swollen joints in the hands, and 11 healthy controls were included. FOI, ultrasound and clinical assessment of both hands were obtained at baseline and for RA patients after 3 and 6 months’ follow-up. Twenty RA patients had an FOI rescan after 4 h. Synovitis was scored using FOIE-GRAS and the OMERACT ultrasound synovitis scoring system. All FOI images were scored by two readers. Inter-scan, inter- and intra-reader reliability were determined. Furthermore, FOIE-GRAS agreement with ultrasound and responsiveness was assessed. Results: FOIE-GRAS synovitis was defined as early enhancement, and scores were based on the degree of coverage of the specific joint region after 3 s (0–3). Inter-scan, intra- and inter-reader intraclass correlations coefficients (ICC) were good to excellent for all baseline scores (0.76–0.98) and moderate to good for change (0.65–76). The FOIE-GRAS had moderate agreement with ultrasound (ICC 0.30–0.54) for total score, a good standardized response mean (>0.80), and moderate correlation with clinical joint assessment and DAS28-CRP. The median (interquartile range) reading time per FOI examination was 133 (109, 161) s. Scores were significantly lower in controls [1 (0, 4)] than RA patients [11 (6, 19)]. Conclusion: The FOIE-GRAS offers a feasible and reliable assessment of synovitis in RA, with a moderate correlation with ultrasound and DAS28-CRP, and good responsiveness.

Background: Subclinical synovitis by ultrasound is a frequent finding in rheumatoid arthritis (RA) patients in remission and has been shown to be related to erosive progression, risk of flare and unsuccessful drug tapering, but it has not been investigated how a DAS28 T2T-steered strategy in routine care affects the presence of subclinical synovitis in RA patients in remission. The aim of the current study was to investigate the presence of ultrasound-detected subclinical inflammation in RA patients in long-term remission receiving either biological or conventional disease-modifying anti-rheumatic drugs (bDMARD/csDMARD) and, finally, to investigate the presence of ultrasound remission using different ultrasound remission criteria. Methods: Eighty-seven RA patients (42 patients receiving bDMARD and 45 csDMARD) received DAS28-CRP-steered treatment in routine care and had achieved DAS28-CRP-remission for > 1 year without radiographic progression. Twenty-four joints were scored 0–3 by ultrasound (elbows, wrists, knees, ankles, metacarpophalangeal and metatarsophalangeal joints 2–5) for grey-scale synovial hypertrophy (GS) and colour Doppler activity (CD) using the OMERACT scoring system. Ultrasound remission was defined as strict (GS score = 0 and CD score = 0), semi-strict (GS score < 1 and Doppler score = 0) and Doppler remission (Doppler score = 0). Results: No differences between treatment groups were found for GS sum score and Doppler sum score (median (range) 6 (0–19) and 0 (0–12), respectively). A Doppler score > 0 in at least 1 joint was seen in 44%, a GS score > 1 in at least 1 joint in 93% and a GS score > 2 in at least 1 joint in 54% of patients. Strict ultrasound remission was only observed in bDMARD patients (7%; p = 0.01). Thirty-seven per cent were in semi-strict ultrasound remission and 56% in Doppler remission (no significant difference between groups) with similar results across the subgroups of patients who also fulfilled the ACR-EULAR Boolean-, CDAI- and SDAI-remission criteria. Conclusions: Ultrasound frequently detected subclinical synovitis in RA patients in longstanding DAS28-remission obtained through a DAS28-CRP-steered strategy. This was independent of treatment and applied ultrasound remission criteria. Strict ultrasound remission was rare.

Rheumatod arthritis is a chronic systemic autoimmune disease, characterized by inflammation in joints and tendon sheaths, which frequently leads to permanent and serious disability due to joint destruction, but also tendon and ligament ruptures. Clinical management of rheumatoid arthritis has traditionally been supported by biochemical and radiographic findings. However, imaging modalities like ultrasound and magnetic resonance imaging (MRI) have improved the possibility for better management of rheumatoid arthritis patients, due to higher sensitivity and specificity for detecting ongoing inflammation, this thesis is focusing on tenosynovitis as recent studies have shown that inflammation in tendon sheaths, i.e. tenosynovitis, is a very common manifestation of rheumatoid arthritis and may often be mistaken for synovitis. Furthermore, presence of ultrasonographic tenosynovitis may predict clinical flare and erosive progression. The main aim of this PhD thesis was to further develop and validate ultrasound as a tool for diagnosis, monitoring and treatment of tenosynovitis. This was investigated in four studies: Study I: 3D Doppler Ultrasound findings in healthy wrist and finger tendon sheaths - Can feeding vessels lead to misinterpretation in Doppler-detected tenosynovitis? Study II: Image fusion of Ultrasound and MRI and B-flow evaluation of tenosynovitis - A pilot study on new imaging techniques in rheumatoid arthritis patients. Study III: Validity and sensitivity to change of the semi-quantitative Outcome Measures in Rheumatology Clinical Trials (OMERACT) ultrasound scoring system for tenosynovitis in patients with rheumatoid arthritis and for the quantitative scoring system, pixel index. Study IV: Intramuscular versus ultrasound guided intratenosynovial glucocorticoid injection for tenosynovitis in patients with rheumatoid arthritis A randomised, double-blind, controlled study with ultrasound and clinical follow up at 4 and 12 weeks.

Objective.: To test the sensitivity to change of the Outcome Measures in Rheumatology Clinical Trials (OMERACT) ultrasound (US) scoring system for tenosynovitis when applied in a multicenter design.Methods.: RA patients with US-verified tenosynovitis were recruited when scheduled for treatment intensification. Tenosynovitis was assessed at baseline, and 3 and 6 months followup, using the semiquantitative OMERACT scoring system.Results.: Expressed in median (25th; 75th percentiles), the overall greyscale and Doppler score decreased significantly from baseline at 4 (2; 7) and 3 (2; 6), to 6 months at 2 (0; 3) and 0 (0; 1, p < 0.01), respectively, and showed high responsiveness (standardized response mean ≥ 0.8).Conclusion.: The OMERACT US scoring system for tenosynovitis showed high responsiveness, supporting its use for diagnosing and monitoring tenosynovitis in multicenter trials.

Aim The aim of this study was to compare the assessment of tenosynovitis by ultrasound (US) and magnetic resonance imaging (MRI) using the image fusion technique and to investigate whether US B-flow imaging (BFI) is an alternative to Doppler US when assessing tenosynovitis. Materials and Methods 15 patients with rheumatoid arthritis (RA) had US-verified tenosynovitis in the wrist/hand. An MRI was performed of the wrist/hand with subsequent repeated US and image fusion. Images were compared in three steps: 1. Visual image comparison, 2. Quantitative measurement of transverse areas of the affected tendon and tendon sheath, using two tendon measures on MRI, area 1 and area 2, excluding and including partial volume artifacts, respectively, 3. Assessment using the OMERACT semi-quantitative scoring systems for US and MRI. Furthermore, BFI was assessed as: 0: No flow, 1: Focal flow, 2: Multifocal flow, 3: Diffuse flow, in the tendon sheath. Results The median areas on US and MRI (areas 1 and 2) were 0.16 cm² (25;75 pctl: 0.10; 0.25), 0.9 cm² (0.06; 0.18) and 0.13 cm² (0.10; 0.25), respectively, for included tendons and 0.18 cm² (0.13; 0.26), 0.27 cm² (0.20; 0.45) and 0.23 cm² (0.16; 0.40) for tendon sheaths. No statistically significant difference was found between US tendon area and MRI tendon area 2 (Wilcoxon’s test; p = 0.47). Overall, the agreement between grayscale and color Doppler (CD) US and MRI tenosynovitis visualization and scoring was good, but not between CD and BFI. Conclusion US and MRI have high agreement using image fusion for the assessment of tenosynovitis when partial volume artifacts are taken into account. BFI is not an alternative to CD for the measurement of slow flow in tenosynovitis. Ziel Das Ziel dieser Studie war es, die Beurteilung der Tenosynovitis mittels Ultraschall (US) und Magnetresonanztomografie (MRT) mittels Bildfusionsverfahren zu vergleichen und zu untersuchen, ob das sonografische B-Flow-Imaging (BFI) eine Alternative zur Dopplersonografie bei der Einstufung der Tenosynovitis darstellt. Material und Methoden 15 Patienten mit rheumatoider Arthritis (RA) hatten eine sonografisch bestätigte Sehnenscheidenentzündung des Handgelenks/der Hand. Eine MRT wurde am Handgelenk/der Hand durchgeführt gefolgt von wiederholten US-Untersuchungen und Bildfusion. Ergebnisse Die medianen Bereiche im US und MRT (Regionen 1 und 2) betrugen für eingeschlossene Sehen 0,16 cm² (25; 75 Perz.: 0,10; 0,25), 0,9 cm² (0,06; 0,18) und 0,13 cm² (0,10; 0,25), und für Sehnenscheiden 0,18 cm² (0,13; 0,26), 0,27 cm² (0,20; 0,45) und 0,23 cm² (0,16; 0,40). Kein statistisch signifikanter Unterschied wurde zwischen dem Sehnenbereich im US und der Sehnenregion 2 in der MRT beobachtet (Wilcoxon-Test; p = 0,47). Schlussfolgerung Insgesamt ergab sich eine gute Übereinstimmung zwischen Graustufen- und Farbdoppler (CD)-US und MRT bei der Darstellung der Tenosynovitis und das Scoring war gut. Allerdings traf dies für CD und BFI nicht zu. Schlussfolgerung: US und MRT zeigen ein hohe Übereinstimmung bei der Anwendung der Bildfusion zur Bewertung der Tenosynovitis, wenn partielle Volumenartefakte mit berücksichtigt werden. BFI ist keine Alternative zum CD bei der Bestimmung des langsamen Flusses bei Tenosynovitis.