Andreas Hansch

Cardiac Involvement in Churg-strauss Syndrome: Impact of Endomyocarditis

Cardiac disease is a major contributor to disease-related death in Churg-Strauss syndrome (CSS). We conducted the current study to determine the prevalence and clinical impact of cardiac involvement in CSS patients. We performed a multicenter, cross-sectional analysis of patients diagnosed with CSS. Cardiac workup included electrocardiography, echocardiography, cardiac magnetic resonance imaging (MRI), and endomyocardial biopsy. We analyzed 49 patients with CSS: 22 patients had clinical evidence of cardiac involvement. A negative antineutrophil cytoplasmic antibodies (ANCA) test and much higher eosinophil counts (9947 vs. 3657/&mgr;L, respectively, p < 0.001) distinguished patients with cardiac involvement from those without. Impaired left ventricular function (50%), mild to severe valvular insufficiencies (73%), and pericardial effusions (41%) were common findings in these patients. Endomyocarditis was found in 13 patients (59%) as detected by cardiac MRI, cardiac thrombus formation, and endomyocardial biopsy, and was associated with impaired cardiac function. After a mean follow-up of 47 months, most patients had regained or maintained good cardiac function. However, patients with endomyocarditis had a more severe outcome. Two patients died (61 and 99 mo after diagnosis, respectively), both due to severe cardiomyopathy and heart failure. Cardiac involvement is common in patients with CSS and is associated with the absence of ANCA and high eosinophil counts. Endomyocarditis may represent the most severe manifestation eventually causing fatal outcome. A structured clinical assessment incorporating cardiac imaging with echocardiography and MRI can identify impaired cardiac function and endomyocardial abnormalities. Abbreviations: ANCA = antineutrophil cytoplasmic antibodies, CSS = Churg-Strauss syndrome, ECG = electrocardiography, FFS = Five Factor Score, IgE = immunoglobulin, LVEF = left ventricular ejection fraction, MRI = magnetic resonance imaging.

Diagnosis of Arthritis Using Near-infrared Fluorochrome Cy5.5

Purpose:Near-infrared range fluorescence (NIRF) imaging is a potential tool to diagnose biologic processes in vivo. This applicability study sought to define whether imaging with fluorochrome Cy5.5 can identify arthritis in murine antigen-induced arthritis (AIA). Materials and Methods:On day 7 of AIA (n = 9 mice), fluorescence intensities in inflamed and contralateral knee joints (the latter as internal control) were measured before and after intravenous injection of Cy5.5 (until 72 hours). Cy5.5 joint deposition was verified by confocal laser-scanning microscopy. Dye phagocytosis was evaluated in cultured macrophages (cell line PMJ2-R) by FACS analysis. Cy5.5 binding to serum protein was tested by NIRF scanning and gel electrophoresis. Results:Between 2 and 72 hours, the arthritic knee joints showed significantly higher fluorescence intensities compared with contralateral joints. Microscopy confirmed Cy5.5 deposition in the synovial membrane. Cultured macrophages actively phagocytosed Cy5.5. Cy5.5 bound mainly to albumin as the main serum protein. Conclusion:NIRF imaging with Cy5.5 can identify arthritic joints in vivo, likely due to nonspecific deposition.

Computerized quantification of joint space narrowing and periarticular demineralization in patients with rheumatoid arthritis based on digital x-ray radiogrammetry.

Objectives:The aim of our work was to evaluate digital x-ray radiogrammetry (DXR) for the quantification of disease-related periarticular demineralization and computerized analysis of joint space distances (JSDA) for the measurement of joint space narrowing as a new diagnostic method for the early detection of joint-associated alterations and for monitoring disease progression in patients with rheumatoid arthritis (RA). Materials and Methods:Digital radiographs in 313 patients with varying severity of RA were performed annually and assessed by 2 radiologists using modified Larsen and also the Sharp scores within an observation period of 3 years. The hand radiographs underwent measurements of bone mineral density (BMD) and metacarpal index (MCI) by DXR, as well as computerized JSDA at the metacarpal-phalangeal articulation (JSD-MCP) for a cross-sectional and longitudinal study design. Results:Both DXR-BMD (−29.6%; P < 0.01) and DXR-MCI (−31.0%; P < 0.01) revealed a notable reduction dependent on the severity of RA (from grade 1 to grade 5 of the modified Larsen score); the severity dependent decrease of mean JSD-MCP ranged from –31.9% (P < 0.01; Sharp erosion part) to −39.1% (P < 0.01) for the modified Larsen score. Over an observation period of 3 years, a significant decrease of DXR-BMD (−22.3%) and DXR-MCI (−23.3%) as well as JSD-MCP mean (−17.5%) was observed (P < 0.05), whereas an accentuated decline of DXR and JSDA parameters was verified for patients without disease-modifying antirheumatic drugs or methotrexate therapy. Conclusion:Computerized analysis of hand radiographs by DXR and JSDA is a promising approach to assess the severity and to monitor the progression of RA because DXR and JSDA are timely able to measure periarticular demineralization and also narrowing of JSD-MCP dependent on the severity, the medical treatment and the course of RA.

Detection and classification of different liver lesions: comparison of Gd-EOB-DTPA-enhanced MRI versus multiphasic spiral CT in a clinical single centre investigation.

OBJECTIVE To compare the diagnostic efficacy of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) vs. multidetector computed tomography (MDCT) for the detection and classification of focal liver lesions, differentiated also for lesion entity and size; a separate analysis of pre- and postcontrast images as well as T2-weighted MRI sequences of focal and exclusively solid lesions was integrated. METHODS Twenty-nine patients with 130 focal liver lesions underwent MDCT (64-detector-row; contrast medium iopromide; native, arterial, portalvenous, venous phase) and MRI (1.5-T; dynamic and tissue-specific phase 20 min after application of Gd-EOB-DTPA). Hepatic lesions were verified against a standard of reference (SOR). CT and MR images were independently analysed by four blinded radiologists on an ordinal 6-point-scale, determining lesion classification and diagnostic confidence. RESULTS Among 130 lesions, 68 were classified as malignant and 62 as benign by SOR. The detection of malignant and benign lesions differed significantly between combined and postcontrast MRI vs. MDCT; overall detection rate was 91.5% for combined MRI and 80.4% for combined MDCT (p<0.05). Considering all four readers together, combined MDCT achieved sensitivity of 66.2%, specificity of 79.0%, and diagnostic accuracy of 72.3%; combined MRI reached superior diagnostic efficacy: sensitivity 86.8%, specificity 94.4%, accuracy 90.4% (p<0.05). Differentiated for lesion size, in particular lesions <20mm revealed diagnostic benefit by MRI. Postcontrast MRI also achieved higher overall sensitivity, specificity, and accuracy compared to postcontrast MDCT for focal and exclusively solid liver lesions (p<0.05). CONCLUSION Combined and postcontrast Gd-EOB-DTPA-enhanced MRI provided significantly higher overall detection rate and diagnostic accuracy, including low inter-observer variability, compared to MDCT in a single centre study.

Combined magnetic resonance imaging of deep venous thrombosis and pulmonary arteries after a single injection of a blood pool contrast agent.

ObjectiveAgreement rate between magnetic resonance imaging (MRI) and Doppler ultrasound (DUS) for the detection of deep vein thrombosis (DVT) in the lower extremities was attempted by using the intravascular MRI contrast agent gadofosveset trisodium. The potential of this method to detect pulmonary embolism (PE) was also evaluated.Material and MethodsForty-three consecutive inpatients with ultrasound-confirmed DVT but no clinical signs of PE were prospectively enrolled in this feasibility study. MRI was performed after a single injection of gadofosveset trisodium. The pulmonary arteries were imaged using a 3D Fast Low Angle Shot (FLASH) gradient recalled echo sequence. Additionally, pulmonary arteries, abdominal veins, pelvic and leg veins were imaged using a fat-suppressed 3D gradient echo Volume Interpolated Breath-hold Examination (VIBE FS).ResultsGadofosveset trisodium-enhanced MRI detected more thrombi in the pelvic region, upper leg and lower leg than the initial DUS. In addition, PE was detected in 16 of the 43 DVT patients (37%).ConclusionThis study shows the feasibility of a combined protocol for the MRI diagnosis of DVT and PE using gadofosveset trisodium. This procedure is not only more sensitive in detecting DVT compared to standard DUS, but is also able to detect PE in asymptomatic patients.

Effect of breast density on computer aided detection.

Purpose: This study was conducted to assess the clinical impact of breast density and density of the lesion’s background on the performance of a computer-aided detection (CAD) system in the detection of breast masses (MA) and microcalcifications (MC). Materials and Methods: A total of 200 screening mammograms interpreted as BI-RADS 1 and suspicious mammograms of 150 patients having a histologically verified malignancy from 1992 to 2000 were selected by using a sampler of tumor cases. Excluding those cases having more than one lesion or a contralateral malignancy attributable to statistical reasons, 127 cases with 127 malignant findings were analyzed with a CAD system (Second Look 5.0, CADx Systems, Inc., Beavercreek, OH). Of the 127 malignant lesions, 56 presented as MC and 101 presented as MA, including 30 cases with both malignant signs. Overall breast density of the mammogram and density of the lesion’s background were determined by two observers in congruence (density a: entirely fatty, density b: scattered fibroglandular tissue, density c: heterogeneously dense, density d: extremely dense). Results: Within the unsuspicious group, 100/200 cases did not have any CAD MA marks and were therefore truly negative (specificity 50%), and 151/200 cases did not have any CAD MC marks (specificity 75.5%). For these 200 cases, the numbers of marks per image were 0.41 and 0.37 (density a), 0.38 and 0.97 (density b), 0.44 and 0.91 (density c), and 0.58 and 0.68 (density d) for MC and MA marks, respectively (Fisher’s t-test: n.s. for MC, p < 0.05 for MA). Malignant lesions were correctly detected in at least one view by the CAD system for 52/56 (92.8%) MC and 91/101 (90.1%) MA. Detection rate versus breast density was: 4/6 (66.7%) and 18/19 (94.7%) (density a), 32/33 (97.0%) and 49/51 (96.1%) (density b), 14/15 (93.3%) and 23/28 (82.1%) (density c), and 2/2 (100%) and 1/3 (33.3%) (density d) for MC and MA, respectively. Detection rate versus the lesion’s background was: 19/21 (90.5%) and 36/38 (94.7%) (density a), 34/36 (94.4%) and 59/62 (95.2%) (density b), 8/9 (88.9%) and 20/24 (83.3%) (density c), and 9/10 (90%) and 4/8 (50%) (density d) for groups 2 and 3, respectively. Detection rates differed significantly for masses in heterogeneously dense and extremely dense tissue (overall or lesion’s background) versus all other densities (Fisher’s t-test: p < 0.05). A significantly lowered FP rate for masses was found on mammograms of entirely fatty tissue. Conclusion: Overall breast density and density at a lesion’s background do not appear to have a significant effect on CAD sensitivity or specificity for MC. CAD sensitivity for MA may be lowered in cases with heterogeneously and extremely dense breasts, and CAD specificity for MA is highest in cases with extremely fatty breasts. The effects of overall breast density and density of a lesion’s background appear to be similar.

Value of digital X-ray radiogrammetry in the assessment of inflammatory bone loss in rheumatoid arthritis

Introduction Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by progressive joint destruction based on the synovitis of large and small joints (1,2). The small joints of the hands and feet are particularly affected in the majority of RA patients, leading to destruction of articular tissue, including cartilage and bone (2). Osteoporosis, a typical phenomenon of RA, occurs in two forms: periarticular osteoporosis, adjacent to the inflamed joints, and generalized osteoporosis, resulting in an increased risk of fractures. Periarticular osteoporosis is a specific feature of bone involvement in RA (3,4) and is one of the bone involvement criteria in addition to erosions in the American College of Rheumatology criteria for RA (5). The onset of periarticular bone loss in the hands and feet is an early sign of RA (6) and may precede erosions (7). Periarticular bone loss is mainly caused by the local release of inflammatory agents and is a direct consequence of the inflammatory process (8), whereas generalized bone loss is additionally influenced by immobility and treatment effects (e.g., glucocorticoids) (9–11). In the hand, inflammatory bone loss includes not only the direct periarticular region of the joints, but also the cortical bone of the metacarpal diaphysis, indicating that inflammation-induced bone loss is present independent of direct synovial contact (12–14). Immunologic aspects of periarticular bone loss in RA

Photodynamic treatment as a novel approach in the therapy of arthritic joints

Minimal invasive local treatment of joints is a desirable option in the therapy of rheumatoid arthritis (RA). Aim of this study was to evaluate the effects of photodynamic treatment (PDT) with different doses of the photosensitizer meta‐tetra(hydroxyphenyl)chlorin (m‐THPC; or temoporfin) in a murine model of RA (antigen‐induced arthritis, AIA).

Magnetic resonance VIBE venography using the blood pool contrast agent gadofosveset trisodium—An interrater reliability study

PURPOSE In this study, image quality of leg veins and vena cava inferior was scored by independent raters using the new intravascular magnetic resonance imaging (MRI) contrast agent gadofosveset trisodium using fat-suppressed 3D gradient echo Volume Interpolated Breath-hold Examination. MATERIAL AND METHODS The leg venous system without clinical signs of deep venous thrombosis (DVT) and sonography-ruled out DVT were imaged using a fat-suppressed 3D gradient echo Volume Interpolated Breath-hold Examination (VIBE FS). Image interpretation was done independently by two experienced radiologists (raters) using a 5-point scoring system. RESULTS High diagnostic image quality with an overall mean visibility score of 4.8±0.1 was acquired in patients enrolled in the study using gadofosveset trisodium-enhanced MRI for the venous system of the leg. There were no cases with moderate, poor or nondiagnostic image quality. Additionally, an excellent interrater reliability was observed. CONCLUSIONS This study shows the feasibility of acquiring high resolution images with excellent image quality of the venous system of the leg using gadofosveset trisodium.

Noninvasive diagnosis of arthritis by autofluorescence.

Rationale and Objectives:The detection of arthritis by autofluorescence was investigated using an antigen-induced arthritis model. Methods:For autofluorescence investigations of joints, a mobile fluorescence-detector was constructed consisting of a lens/mirror system attached to a conventional spectrofluorometer and optimized fiber optic cables reaching to and from the site of investigation. Autofluorescence measurements were performed at 7 arthritic and 7 healthy mice. Fifteen antigen-induced arthritis and 3 healthy mice were used for histologic examinations. Results:In the exudative stage (day 1), a decrease of emission signal intensities for excitation wavelengths at 300 nm (emission, 355–365 nm) and 360 nm (emission, 475–485 nm) was observed. Signals increased on day 7 (maximum of cellular infiltration). Chronic inflammation (day 14 and 21) led to a decrease of signals again. Conclusion:Arthritis influences autofluorescence signals in vivo. The detected excitation/emission pairs can be assigned to collagen/elastin and NAD(P)H. Signal intensities of NAD(P)H differed significantly from controls at day 1 and 7.