Alexander K. Scheel

For development and test of new optical imaging devices, phantoms are widely used to emulate the tissue to be imaged. Phantom design gets more difficult the more complex the tissue is structured. We report on developing and testing a solid, stable finger joint phantom to simulate transillumination of finger joints in frequency-domain imaging systems. The phantom consists of the bone, capsule, skin, the capsule volume, and the joint gap. Silicone was used to build the solid parts and a glycerol-water solution for the fluid in the capsule volume and joint gap. The system to test the phantom is an optical frequency-domain scanning set-up. Different stages of joint inflammation as they occur in rheumatoid arthritis (BA) were emulated by assembling the phantom with capsule and fluid having different optical properties. Reliability of the phantom measurement was investigated by repeated assembling. The results show clear discrimination between different stages of joints within the signal deviation due to reassembling of the phantom

For development and test of new optical imaging devices, phantoms are widely used to emulate the tissue to be imaged. Phantom design gets more difficult the more complex the tissue is structured. We report on developing and testing a solid, stable finger joint phantom to simulate transillumination of finger joints in frequency-domain imaging systems. The phantom consists of the bone, capsule, skin, the capsule volume, and the joint gap. Silicone was used to build the solid parts and a glycerol-water solution for the fluid in the capsule volume and joint gap. The system to test the phantom is an optical frequency-domain scanning set-up. Different stages of joint inflammation as they occur in rheumatoid arthritis (BA) were emulated by assembling the phantom with capsule and fluid having different optical properties. Reliability of the phantom measurement was investigated by repeated assembling. The results show clear discrimination between different stages of joints within the signal deviation due to reassembling of the phantom

Die Arthrosonographie hat sich in der Rheumatologie als bildgebendes Verfahren insbesondere zur Darstellung früh entzündlicher Veränderungen etabliert. Als Nachteil wird hervorgehoben, dass es sich hierbei um ein stark untersucherabhängiges Verfahren handelt, was jedoch bisher nie systematisch untersucht wurde. Auf der anderen Seite gilt die Magnetresonanztomographie als weniger untersucherabhängig. Entgegen bisheriger Meinungen konnte jedoch kürzlich in Studien gezeigt werden, dass moderate bis gute Übereinstimmung zwischen den Untersuchern vorliegen. Die für die Arthrosonographie erhobenen Kappa-Werte als Ausdruck der Untersucherübereinstimmung waren vergleichbar mit den in Magnetresonanztomographiestudien erhobenen Werten. Die Studien zeigen jedoch auch, dass eine dynamische Untersuchung aller Gelenke vermehrt durchgeführt und die palmare und dorsale Seite der Fingergelenke miteinbezogen werden sollte. Zur arthrosonographischen Differenzierung zwischen gesunden und pathologischen Strukturen ist annäherungsweise der Mittelwert der gesunden Strukturen mit einer 2fachen Standardabweichung anzuwenden, genauer ist eine Differenzierung unter Hinzunahmen von pathologischen Strukturen nach Berechnung mit ROC-Kurven möglich. Musculoskeletal ultrasonography has become an established imaging technique in rheumatology, especially in the detection of early inflammation. It has been stated that the main disadvantage is its examiner-dependency. However, an inter-reader reliability between a larger number of ultrasonographers has not yet been systematically evaluated. Contrary to previous opinions, recent studies showed moderate to good inter-observer reliabilities between ultrasonographers. The kappa values were comparable to those achieved by radiologists evaluating magnetic resonance imaging. However, the studies also show that a dynamic examination of all joints and an inclusion of the palmar and dorsal sides of the finger joints are necessary. In musculoskeletal ultrasonography a differentiation between healthy and pathological tissue can roughly be performed by taking the mean with a 2-fold standard deviation of healthy tissue, a more precise cut-off can be calculated by ROC analysis with the necessity of adding data of pathological tissue.

Objective: To perform a prospective long term follow up study comparing conventional radiography (CR), ultrasonography (US), and magnetic resonance imaging (MRI) in the detection of bone erosions and synovitis in rheumatoid arthritis (RA) finger joints. Methods: The metacarpophalangeal and proximal interphalangeal joints II–V (128 joints) of the clinically dominant hand of 16 patients with RA were included. Follow up joint by joint comparisons for erosions and synovitis were made. Results: At baseline, CR detected erosions in 5/128 (4%) of all joints, US in 12/128 (9%), and MRI in 34/128 (27%). Seven years later, an increase of joints with erosions was found with CR (26%), US (49%) (pConclusion: After 7 years, an increase of bone erosions was detected by all imaging modalities. In contrast, clinical improvement and regression of synovitis were seen only with US and MRI. More than one third of erosions previously detected by MRI were seen by CR 7 years later.

Objective: To evaluate the interobserver reliability among 14 experts in musculoskeletal ultrasonography (US) and to determine the overall agreement about the US results compared with magnetic resonance imaging (MRI), which served as the imaging “gold standard”. Methods: The clinically dominant joint regions (shoulder, knee, ankle/toe, wrist/finger) of four patients with inflammatory rheumatic diseases were ultrasonographically examined by 14 experts. US results were compared with MRI. Overall agreements, sensitivities, specificities, and interobserver reliabilities were assessed. Results: Taking an agreement in US examination of 10 out of 14 experts into account, the overall κ for all examined joints was 0.76. Calculations for each joint region showed high κ values for the knee (1), moderate values for the shoulder (0.76) and hand/finger (0.59), and low agreement for ankle/toe joints (0.28). κ Values for bone lesions, bursitis, and tendon tears were high (κ = 1). Relatively good agreement for most US findings, compared with MRI, was found for the shoulder (overall agreement 81%, sensitivity 76%, specificity 89%) and knee joint (overall agreement 88%, sensitivity 91%, specificity 88%). Sensitivities were lower for wrist/finger (overall agreement 73%, sensitivity 66%, specificity 88%) and ankle/toe joints (overall agreement 82%, sensitivity 61%, specificity 92%). Conclusion: Interobserver reliabilities, sensitivities, and specificities in comparison with MRI were moderate to good. Further standardisation of US scanning techniques and definitions of different pathological US lesions are necessary to increase the interobserver agreement in musculoskeletal US.

Objective: To develop an ultrasonographic (US) synovitis scoring system suitable for evaluation of finger joint inflammation in patients with active rheumatoid arthritis (RA) and to compare semiquantitative US scoring with quantitative US measurements.Methods: US was performed at the palmar and dorsal sides of the second through fifth metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints in 10 healthy subjects and in the clinically more affected hand in 46 RA patients. Ten patients additionally underwent magnetic resonance imaging (MRI). Synovitis was measured, standardized, and scored according to a semiquantitative method. The 2 methods (semiquantitative US scoring, quantitative US) were compared and statistical cutoffs were identified using receiver operating characteristic (ROC) curve analysis. MRI results were compared with semiquantitative US scoring and quantitative US results. The optimal US scoring method from 6 joint combinations was identified (ROC curve analysis).Results: Synovitis was most frequently detected in the palmar proximal area (86% of affected joints). We found no significant differences between individual PIP joints or between individual MCP joints, indicating that all fingers within each of these joint groups should be treated equally for statistical calculations, although each joint group as a whole should be treated separately. The optimal cutoff point to distinguish between “health” and “pathology” was 0.6 mm both for MCP joints (sensitivity 94%, specificity 89%) and for PIP joints (sensitivity 90%, specificity 88%). There was no significant difference between semiquantitative US scores and quantitative US measurements. The best results for joint combinations were achieved using the “sum of 4 fingers” (second through fifth MCP and PIP joints) and “sum of 3 fingers” (second through fourth MCP and PIP joints) methods. Comparison of MRI results with semiquantitative US scores revealed high concordance.Conclusion: US evaluation of finger joint synovitis can be considerably simplified by focusing on the palmar side and by applying semiquantitative grading instead of quantitative measurements. For evaluation of treatment efficacy based on synovitis in RA patients, we recommend using the “sum of 3 fingers” method in longitudinal trials.

Objective: To identify classifiers in images obtained with sagittal laser optical tomography (SLOT) that can be used to distinguish between joints affected and not affected by synovitis. Methods: 78 SLOT images of proximal interphalangeal joints II–IV from 13 patients with rheumatoid arthritis were compared with ultrasound (US) images and clinical examination (CE). SLOT images showing the spatial distribution of scattering and absorption coefficients within the joint cavity were generated. The means and standard errors for seven different classifiers (operator score and six quantitative measurements) were determined from SLOT images using CE and US as diagnostic references. For classifiers showing significant differences between affected and non-affected joints, sensitivities and specificities for various cut off parameters were obtained by receiver operating characteristic (ROC) analysis. Results: For five classifiers used to characterise SLOT images the mean between affected and unaffected joints was statistically significant using US as diagnostic reference, but statistically significant for only one classifier with CE as reference. In general, high absorption and scattering coefficients in and around the joint cavity are indicative of synovitis. ROC analysis showed that the minimal absorption classifier yields the largest area under the curve (0.777; sensitivity and specificity 0.705 each) with US as diagnostic reference. Conclusion: Classifiers in SLOT images have been identified that show statistically significant differences between joints with and without synovitis. It is possible to classify a joint as inflamed with SLOT, without the need for a reference measurement. Furthermore, SLOT based diagnosis of synovitis agrees better with US diagnosis than CE.

Anamnese und klinischer Befund: Bei einer 55-jährigen Patientin bestanden seit Jahren Schmerzen und Schwäche im Bereich beider unterer Extremitäten. Aufgrund einer hypothalamischen Raumforderung unklarer Ätiologie entwickelten sich ein therapiebedürftiger zentraler Diabetes insipidus, eine gonadotrope und somatotrope Insuffizienz sowie eine partielle kortikotrope Insuffizienz. Untersuchungen: Laborchemisch bestand eine Entzündungskonstellation (Erhöhung von BSG, CRP, Fibrinogen und Thrombozyten). Serologische Parameter, die für eine rheumatische Systemerkrankung gesprochen hätten, waren nicht nachweisbar. Bei der konventionellen Röntgenuntersuchung ergaben sich osteolytisch-osteoblastische Knochenstrukturveränderungen im distalen Bereich beider Femora sowie in den proximalen Tibiae mit Signalalterationen im MRT und skelettszintigraphisch einer massiven Anreicherung von ^99mTechnetium. Histopathologisch wurden in einer Knochenbiopsie von der linken Tibia multifokale kleinherdige Infiltrate aus schaumzelligen Histiozyten als morphologisches Substrat einer Erdheim-Chester-Krankheit (ECD) nachgewiesen. Therapie und Verlauf: Unter einer Therapie mit Kortikosteroiden besserten sich die muskuloskelettalen Beschwerden, die sich jedoch nach Dosisreduktion erneut verstärkten. Ein Therapieversuch mit Methotrexat brachte keine Befund- oder Beschwerdebesserung. Folgerung: Das Erdheim-Chester-Syndrom wird den Erkrankungen mit einer Proliferation des monozytär-histiozytären und dendritischen Zellsystems zugerechnet. Bei Vorliegen symmetrischer muskuloskelettaler Beschwerden mit gemischten osteosklerotischen und osteolytischen Veränderungen vor allem der langen Röhrenknochen der unteren Extremitäten sollte bei gleichzeitiger Erhöhung der Entzündungswerte differenzialdiagnostisch auch an eine ECD gedacht werden. Eine gesicherte Therapie gibt es derzeit nicht. History and clinical findings: A 55-year-old female was admitted complaining of musculoskeletal pain and weakness of both lower extremities for a number of years. Due to a hypothalamic mass of unknown aetiology a diabetes insipidus, a gonadotrophic, somatotrophic and a partially corticotrophic insufficiency had developed. Investigations: Laboratory investigations yielded elevated levels of several inflammatory parameters (C-reactive protein, blood sedimentation rate, fibrinogen and thrombocytes). Serological parameters indicating a systemic rheumatic disorder were absent. X-ray examination revealed combined osteolytic and osteoblastic lesions within the distal parts of both femora and within the proximal portions of both tibiae. MRI showed signal alterations and ^99mTechnetium bone scan exhibited a considerably increased uptake. Histopathologically, a biopsy of the left tibia showed multifocal small infiltrates of foamy histiocytes indicating Erdheim-Chester disease (ECD). Treatment and course: Under treatment with glucocorticosteroids musculoskeletal complaints improved, but re-appeared following dose reduction. A therapeutic trial using methotrexat did not affect the complaints. Conclusion: The Erdheim-Chester syndrome is considered to belong to diseases with a proliferation of the monocytic-histiocytic and dendritic cellular system. In the presence of symmetric musculoskeletal symptoms associated with osteosclerotic and osteolytic lesions particularly occurring in the long bones of the lower extremities and concomitant with elevated serum markers of inflammation, the Erdheim-Chester disease should be taken into account. To date, no validated therapy exists.

Objectives: To evaluate the correlation of MRI and [¹⁸F]FDG-PET scans with the clinical course and inflammatory markers in patients with aortitis. Methods: Eight patients with aortitis presenting with unspecific GCA-like symptoms were examined. Aortitis was diagnosed and followed up by [¹⁸F]FDG-PET and MRI. The aorta was divided into three vascular regions (ascending aorta, aortic arch, and descending aorta) to localise the aortic inflammation and compare both imaging techniques. Results were correlated with clinical and laboratory examinations. Results: At diagnosis, 20/24 vascular regions from eight patients were positive by [¹⁸F]FDG-PET scan and 15/21 aortic regions by MRI. Patients were treated with corticosteroids and followed up for a mean (SD) of 13.3 (4.7) months. In [¹⁸F]FDG-PET, 11/20 (55%) initially pathological aortic regions returned to normal in the follow up examination, which correlated closely with the clinical and laboratory follow up examination. Conversely, in MRI, 14/15 initially affected vascular regions were unchanged. Conclusions: [¹⁸F]FDG-PET and MRI are both effective techniques for detecting early aortitis and have a high correlation with laboratory inflammatory measures. However, during the follow up examination, [¹⁸F]FDG-PET uptake decreased in line with the clinical symptoms and inflammatory serum markers, whereas MRI scans gave more static results.

Muskuläre Hyperkinesen lassen sich sonographisch darstellen: Am besten untersucht ist die sonographische Erfassung von Faszikulationen, aber auch so genannte ripplings, Myoklonien, choreatische Hyperkinesen und Tremores können sonographisch erfasst werden. Die Myosonographie hat sich besonders für den Nachweis von Faszikulationen als sehr geeignetes Verfahren herausgestellt. Faszikulationen zeigen sich sonographisch als 0,2 bis 0,5 Sekunden andauernde lokalisierte Muskelzuckungen. Einige Myoklonien ähneln sonographisch den Faszikulationen, andere zeigen eine längere Zuckungsdauer. Die Sonographie erlaubt eine sehr einfache und zuverlässige Bestimmung von Tremorfrequenzen. Die vorliegende Arbeit fasst den aktuellen Kenntnisstand zur sonographischen Detektion muskulärer Hyperkinesen zusammen und zeigt Zukunftsperspektiven auf. Muscular hyperkinesias can be visualized by means of ultrasound (US): Ultrasonographic detection of fasciculations has been best evaluated. However, so-called ripplings, myoclonias and choreatic hyperkinesias as well as tremores can also be visualized by US. Muscular US has proven as a precise imaging technique for the detection of fasciculations. Fasciculations are brief, localized muscle twitches, usually lasting for 0.2 - 0.5 seconds. Some myoklonias may present similar in US, others present with a longer duration. In addition, muscle US allows a very easy and reliable detection of tremor frequency. This article reviews the present ultrasonographic facilities in the detection of muscular hyperkinesias and gives future perspectives.