Inflammatory Changes In Joints Research Articles

Computed tomography-current status and future directions for arthritis imaging.

Applications of computed tomography (CT) in arthritis imaging have rapidly expanded in recent years due to ongoing technical developments. Dual-energy CT (DECT) has become indispensable in clinical practice, particularly for diagnosing gouty arthritis and assessing bony structural changes. Technological innovations such as low-dose CT and state-of-the-art reconstruction algorithms reduce radiation exposure while maintaining image quality and short acquisition times. This review explores the growing role of CT in arthritis imaging. Recent innovations have extended DECT's utility beyond gout diagnosis to the detection of inflammatory changes in various arthritic conditions. Postprocessing techniques such as the generation of subtraction images and iodine maps provide valuable insights into tissue perfusion and inflammatory activity, crucial for arthritis management. DECT can distinguish calcium from uric acid crystals, facilitating the differential diagnosis of various crystal arthropathies in a variety of clinical settings. This ability is particularly valuable in distinguishing between different clinical conditions in patients with inflammatory joint changes within a single imaging examination. Moreover, the advent of four-dimensional CT promises a better assessment of dynamic joint instabilities and ligament injuries, especially in the wrist. Overall, DECT offers a comprehensive approach to arthritis imaging, from the detection of structural changes to the assessment of active inflammation in joints and tendons. Continuous advances in CT technology, including photon-counting CT, hold promise for further improving diagnostic accuracy and expanding the role of CT in arthritis imaging and therapy monitoring.

Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of Osteoarthritis.

Progressive articular surface degradation during arthritis causes ongoing pain and hyperalgesia that lead to the development of functional disability. TRPA1 channel significantly contributes to the activation of sensory neurons that initiate neurogenic inflammation and mediates pain signal transduction to the central nervous system. Peptide Ms 9a-1 from the sea anemone Metridium senile is a positive allosteric modulator of TRPA1 and shows significant anti-inflammatory and analgesic activity in different models of pain. We used a model of monosodium iodoacetate (MIA)-induced osteoarthritis to evaluate the anti-inflammatory properties of Ms 9a-1 in comparison with APHC3 (a polypeptide modulator of TRPV1 channel) and non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam and ibuprofen. Administration of Ms 9a-1 (0.1 mg/kg, subcutaneously) significantly reversed joint swelling, disability, thermal and mechanical hypersensitivity, and grip strength impairment. The effect of Ms 9a-1 was equal to or better than that of reference drugs. Post-treatment histological analysis revealed that long-term administration of Ms9a-1 could reduce inflammatory changes in joints and prevent the progression of cartilage and bone destruction at the same level as meloxicam. Peptide Ms 9a-1 showed significant analgesic and anti-inflammatory effects in the model of MIA-induced OA, and therefore positive allosteric modulators could be considered for the alleviation of OA symptoms.

CD10-Bound Human Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles Possess Immunomodulatory Cargo and Maintain Cartilage Homeostasis under Inflammatory Conditions.

The onset and progression of human inflammatory joint diseases are strongly associated with the activation of resident synovium/infrapatellar fat pad (IFP) pro-inflammatory and pain-transmitting signaling. We recently reported that intra-articularly injected IFP-derived mesenchymal stem/stromal cells (IFP-MSC) acquire a potent immunomodulatory phenotype and actively degrade substance P (SP) via neutral endopeptidase CD10 (neprilysin). Our hypothesis is that IFP-MSC robust immunomodulatory therapeutic effects are largely exerted via their CD10-bound small extracellular vesicles (IFP-MSC sEVs) by attenuating synoviocyte pro-inflammatory activation and articular cartilage degradation. Herein, IFP-MSC sEVs were isolated from CD10High- and CD10Low-expressing IFP-MSC cultures and their sEV miRNA cargo was assessed using multiplex methods. Functionally, we interrogated the effect of CD10High and CD10Low sEVs on stimulated by inflammatory/fibrotic cues synoviocyte monocultures and cocultures with IFP-MSC-derived chondropellets. Finally, CD10High sEVs were tested in vivo for their therapeutic capacity in an animal model of acute synovitis/fat pad fibrosis. Our results showed that CD10High and CD10Low sEVs possess distinct miRNA profiles. Reactome analysis of miRNAs highly present in sEVs showed their involvement in the regulation of six gene groups, particularly those involving the immune system. Stimulated synoviocytes exposed to IFP-MSC sEVs demonstrated significantly reduced proliferation and altered inflammation-related molecular profiles compared to control stimulated synoviocytes. Importantly, CD10High sEV treatment of stimulated chondropellets/synoviocyte cocultures indicated significant chondroprotective effects. Therapeutically, CD10High sEV treatment resulted in robust chondroprotective effects by retaining articular cartilage structure/composition and PRG4 (lubricin)-expressing cartilage cells in the animal model of acute synovitis/IFP fibrosis. Our study suggests that CD10High sEVs possess immunomodulatory miRNA attributes with strong chondroprotective/anabolic effects for articular cartilage in vivo. The results could serve as a foundation for sEV-based therapeutics for the resolution of detrimental aspects of immune-mediated inflammatory joint changes associated with conditions such as osteoarthritis (OA).

Immunosenescence of T cells: a key player in rheumatoid arthritis.

The incidence of rheumatoid arthritis (RA) and its complications are expected to increase with age. Remarkably, RA patients were identified features of accelerated aging, particularly in immunosenescence. As is known, T cells in RA patients readily differentiate into pro-inflammatory phenotypes that maintain chronic and persistent inflammatory changes in joints and many other organ systems. Recent evidence suggests that T cells are most sensitive to aging, and aged CD4+ T cells contribute to inflammaging, which plays a crucial role in accelerating the disease process. In recent years, the molecular mechanisms of T cell immunosenescence were beginning to be understood. Immune aging in RA T cells is associated with thymus insufficiency, metabolic abnormalities, shortened telomere length, and chronic energy stress. Therefore, we summarized the role and mechanism of T cell immunosenescence in RA. A computer-based online search was performed using the PubMed database for published articles concerning T cells aging and rheumatoid arthritis. In this review, we assess the roles of CD4+ T cells in the center of inflammaging especially in RA and emphasize arthritogenic effector functions of senescent T cell; also we discuss the possible molecular mechanisms of senescent T cells and therapeutic targets to intervene T cells immunosenescence for improvement of RA.

Dynamics of synovitis activity after intraarticular administration of xefocam in patients with rheumatoid arthritis

The aim of the study was to assess the efficacy of intra-articular injection of lornoxicam (xefocam, Nycomed) in patients with rheumatoid arthritis. Xefocam was injected into knee joints of 15 patients with rheumatoid arthritis, 8 mg once a week for the period of 3 weeks. The following parameters were assessed: pronouncement of arthralgia, joint tenderness at palpation, circumference of knee joint on the level of the upper patellar margin. Prior and post treatment ultrasonography and thermography were used. Significant clinical improvement was observed in 11 patients. In 3 cases the dynamics was less positive and in 1 patients the effect of single dose drug injection was preserved for less than one week. Arthralgia manifestation (p0.01), joint tenderness at palpation (p0.01) and joint circumference (p0.05) showed reliable decrease. Ultrasonography showed reliable decrease the synovial membrane thickness. Xefocam injection could be successfully used to suppress moderate inflammatory joint changes in patients with rheumatoid arthritis when there are no strict indications to local steroid therapy.

Assessment of pain in rheumatoid arthritis. Practical significance

The chief complaint of patients with rheumatoid arthritis (RA) is pain. The latter is one of the main signs of chronic inflammation, which holds a central position in the clinical picture of the disease. Pain is not among the baseline parameters that are used to calculate total disease activity indices. Nevertheless, pain greatly influences the result of RA activity determination using the total indices. However, this assessment system can take into account only the intensity of pain, whereas the clinical significance of pain syndrome is largely determined by its nature. The causes of pain in RA can be different in different patients and even in one patient at early and late stages of the disease, during the periods of exacerbation and attenuation of the inflammatory activity. Pain in RA is not always associated with the active inflammatory process. At the same time, intense non-inflammatory pain can significantly affect the traditional indicators of inflammatory activity, by distorting the result of quantitative determination of disease activity. In turn, an erroneous activity assessment may cause an incorrect choice of treatment policy. Therefore, the clinical use of tools that reliably determine the nature of pain, can contribute to a significant improvement in the quality of care for RA patients. In most cases pain in RA is associated with inflammatory changes in joints or periarticular soft tissues. Therefore along with disease-modifying anti-rheumatic drugs, nonstreroidal anti-inflammatory drugs (NSAIDs) are widely used in the combination therapy of RA. However, their use is limited by a risk of adverse reactions. Etoricoxib is one of the highly effective drugs with a good safety profile. Currently, there are no recommendations for the treatment of neuropathic pain in patients with RA. Investigating the efficacy of tricyclic antidepressants and cannabinoids in RA has failed to prove their advantages over placebo.

Psoriasis vs. psoriatic arthritis : Similarities and differences in the pathophysiology

Psoriasis is achronic inflammatory skin disease with genetic and (auto)immunological backgrounds. Up to 30% of patients with psoriasis also develop amostly oligoarticular arthritis with spinal involvement that is termed psoriatic arthritis (PsA) and shows aspecific joint pattern which differs from that of rheumatoid arthritis (RA). Both Psa and psoriasis share acommon main axis, the interleukin (IL) 23/IL17 pathway as well as major overlaps in the functions of tumor necrosis factor alpha (TNFalpha). Recently acquired knowledge supports the concept that in both diseases, similar genetic dispositions and molecular pathways lead to organ-specific disease patterns. In some types of PsA, genetic predisposition and the relevance of acute inflammatory reactions appear to be greater that in psoriasis, while in the latter exogenous factors and T‑lymphocyte reactions in the skin seem to have a higher impact. Akey difference between PsA and cutaneous psoriasis is the largely irreversible nature of inflammatory joint changes in PsA, whereas cutaneous plaques in psoriasis completely heal. The question of how interdependent both diseases are and whether immunologically primed T‑lymphocytes from cutaneous lesions in PsA may transmit the disease to the synovial membranes and induce acute inflammation is not precisely known. Adetailed analysis of these organ-specific differences may not only provide an explanation for the similar, but partly different efficacy of novel therapeutic strategies but may also lead to the development of personalized therapies that take into account the individually different manifestations of the diseases over time.

Non-invasive dual fluorescence in vivo imaging for detection of macrophage infiltration and matrix metalloproteinase (MMP) activity in inflammatory arthritic joints.

Detection and intervention at an early stage is a critical factor to impede arthritis progress. Here we present a non-invasive method to detect inflammatory changes in joints of arthritic mice. Inflammation was monitored by dual fluorescence optical imaging for near-infrared fluorescent (750F) matrix-metalloproteinase activatable agent and allophycocyanin-conjugated anti-mouse CD11b. Increased intensity of allophycocyanin (indication of macrophage accumulation) and 750F (indication of matrix-metalloproteinase activity) showed a biological relationship with the arthritis severity score and the histopathology score of arthritic joints. Our results demonstrate that this method can be used to detect early stages of arthritis with minimum intervention in small animal models.

Systemic sclerosis - a multi-purpose use of ultrasound: Editorial comment on: G. Pracoń, M. Płaza, M. Walentowska-Janowicz, I. Sudoł-Szopińska The value of ultrasound in the diagnosis of limited scleroderma - a case report.

Sysyemic sclerosis (SSc) is a chronic connective tissue disease characterized by multi-organ involvement. In its variants, SSc may affect the skin, vessels, the heart, joints and the lungs. As such, it is potentially available for ultrasound examination in a wide field of applications. With the most modern linear high-frequency transducers, it has become feasible to examine the skin in patients with SSc. US makes it possible to measure the thickness of the skin and subcutaneous tissue thereby helping determine the potential skin involvement and its range, and differentiate the localized from diffuse forms of SSc(1). Moreover, the examination of dermal thickness and echogenicity may be helpful in stratifying SSc into the edematous, fibrotic and atrophic phases of skin involvement(2). Elastosonography, a method combining the assessment of ultrasound and elastic properties of the tissue, is also shown to be a promising technique in SSc(3). Raynaud phenomenon and vascular involvement in SSc may be the primary events, even preceding skin affection. The assessment of the vessels is therefore of cardinal significance in SSc. A Doppler analysis of flow in patients suspected of SSc may reveal if Raynaud phenomenon is of primary or secondary character(4). The anatomical features of vessels may also help in the analysis of Raynaud phenomenon(5). Furthermore, as atherosclerosis is more prevalent in patients with SSc, the assessment of carotid plaques with US(6) may induce earlier prophylaxis in this group of patients. This assumption is strengthened by more frequent subclinical heart involvement in patients with SSc compared with healthy controls, as assessed with echocardiography(7), yet another application of US in this disease. In the rheumatologic world, it is obviously the musculoskeletal system that receives the most attention. And it is also like that in rheumatology-related US. Pain in the musculoskeletal system is frequently reported in patients with SSc. Until recently, it has been considered neither to be inflammatory nor leading to erosive joint disease. US supports though that the reason for pain can be detected and visualized. In studies comparing patients with SSc, rheumatoid arthritis (RA) and healthy controls, it has been shown that inflammatory joint changes occur as often as in joints of patients with RA(8). Synovial proliferation, joint effusion and tendinitis were reported, and only Doppler signal and erosive joint disease were more frequent in patients with RA. In a study by Chitale et al., US findings in the hands of patients with SSc were compared with magnetic resonance imaging (MRI)(9). The latter showed both more inflammatory changes than US and bone erosions, which were not detected with US. Tendon involvement was assessed in a study by Elhai et al. and signs of tendinitis were more frequent in patients with SSc in comparison with RA patients(10). Another study by Cuomo et al. also presented characteristic features of tendon and retinaculum involvement showing a hyperechoic pattern(11). In many SSc patients, interstitial pulmonary fibrosis (IPF) is a significant manifestation of the disease and a frequent cause of death. The method of choice for assessment and follow-up of IPF is high-resolution computed tomography (HRCT). The need for frequent assessments and the increasing radiation dose of SSc patients with lung affection makes the use of US, with a potential support of HRCT, particularly attractive in long-term monitoring as a non-radiation method. A significant correlation of findings in US, HRCT score and diffusion capacity of the lungs to carbon monoxide test in a study by Tardella et al.(12), as well as other authors(13, 14), makes the possibility feasible. The elementary lesions in US assessment of patients with IPF are B-lines, i.e. vertical reverberation artifacts, also called comet tails, generated by the reflection of the US beam from thickened subpleural interlobular septa detectable in the lung intercostal spaces. But still, the skin is the most dominant and frequently affected organ in SSc. The authors of the paper in “Journal of Ultrasonography” deal with an aspect of SSc that is seldom investigated(15). Grzegorz Pracon et al. report on characteristic ultrasound features of hydroxyapatite deposits in a finger of a patient with limited SSc. It is an original finding which, when applied in practice, may lead to a quick surgical intervention and alleviation of the patient's symptoms. The present study, seen in relation to the available research results, stresses the need for further and more detailed assessment of patients with SSc in the hope of quicker diagnosis, detecting complications and potential monitoring of the disease and its treatment.

Characterization of articular syndrome under conditions of psoriatic arthropathy, opportunities of different imaging techniques

The variability of the clinical picture of psoriatic arthritis, commonality with other diseases of the joints creates great difficulties in the way of timeous diagnostics of this pathology. Objective: To study peculiarities of articular syndrome, the diagnostic value of radiography, magnetic resonance imaging and ultrasonography in patients with psoriatic arthropathy. Methods: 100 patients with psoriatic arthritis with severe articular syndrome, combined with the typical lesions of the skin, scalp or psoriatic onihodystrophy were included in this study. Patients underwent radiological, ultrasound and magnetic resonance imaging of the joints. Results: It was found that distal parts of the hands and feet are the most common localizations of articular syndrome in patients with psoriatic arthritis. In men, the number of affected joints was reliably higher than that of women, and psoriatic arthritis predominates. In patients under 40 years lesion of the distal portions of the hands and feet dominates, and for patients over 60 years polyarthritic option is more typical. According to the radiological study in 72 % of patients fitted inflammatory changes in joints, and in 28 % of them — associated degenerative-dystrophic and inflammatory changes. Magnetic resonance imaging and ultrasonography diagnosed thinning or thickening of the hyaline cartilage as well as tendons on the background of tendovaginitis. Advantages of magnetic resonance imaging comparing to sonography has not been established. Conclusions: In patients with psoriatic arthropathy screening method is radiography. To assess the state of hyaline cartilage and tendons an MRI or sonography of joints should be given although magnetic resonance imaging has no any advantages comparing to ultrasonography.

EXPERIENCE OF THE ADALIMUMAB APPLICATION FOR THE PATIENT WITH EARLY DEBUT OF JUVENILE IDIOPATHIC ARTHRITIS AND UVEITIS

The case of early debut and heavy course of juvenile idiopathic arthritis in the patient at the age of 1 year and 8 months, associated with uveitis refractory to the therapy by methotrexate and nonsteroid antiinflammatory preparations is presented. The given clinical example shows high therapeutic efficiency of the adalimumab. To the 8th week of treatment inflammatory changes in conjunctiva were stopped, to the 12th week the stage of inactive illness was registered, i.e. the patient had no inflammatory changes in joints, uveitis activity signs, increase of laboratory indicators of illness activity. Duration of remission of articulate syndrome and uveitis made 9 months.

GENNO-INZhENERNYE BIOLOGIChESKIE PREPARATY V TERAPII OSTEOPOROZA U BOL'NYKhREVMATOIDNYM ARTRITOM

The authors review the current literature data on the influence of the genetically engineered biological drugs on the bone mineral density, bone exchange and remodeling of bone are submitted. Due to high efficiency these drugs received the deserved popularity in spite of the fact that are applied in rheumatology rather recently. The leading role in pathogenesis of local and generalized bone resorption and destruction in rheumatoid arthritis is realized by mediators of immune and inflammatory processes (pro-inflammatory cytokinins): tumor necrosis factor a, interleukin 1, 2, 12, 17, interferon γ, and also prostaglandins, proteolytic enzymes (a collagenase, other proteases), etc. There are described RANKL — dependent and RANKL — independent mechanisms of activation the osteoclastogenesis. In recent years it is established that the inhibition of pro-inflammatory cytokinins not only reduces inflammatory changes of joints, but also constrains destruction development, interferes with development of bone erosions and generalized bone loss. In the present review results of these works are discussed and questions for future researches are brought up.

AB1295 Ultrasound assessment at patients with late onset of rheumatoid arthritis: Higher scores of inflammation activity of joint compared to early onset of rheumatoid arthritis

BackgroundGrowing evidence supports the hypothesis that in elderly onset of rheumatoid arthritis (RA) patients (pts) showed higher sonographic scores of inflammation despite similar clinical disease activity compared to in young...

Erosive and inflammatory joint changes in hereditary hemochromatosis arthropathy detected by low-field magnetic resonance imaging

The aim of the article is to describe and characterize the hemochromatosis arthropathy of the hand by low-field MRI in symptomatic and asymptomatic patients. Forty-nine patients with hereditary hemochromatosis (37 with and twelve without arthropathy) were examined clinically and by low-field MRI of the hands. The examination showed heterogeneous degenerative and inflammatory joint changes such as erosions (in 84% of all symptomatic patients), synovitis (77%), bone marrow edema (38%), subchondral cysts (30%), tenosynovitis (30%), joint space narrowing (73%) and osteophytes (59%) including hook-shaped osteophytes at MCP joints (32%). Mild joint changes were also seen in a lower percentage of asymptomatic patients. This is the first larger study addressing the joint changes of the hand in hereditary hemochromatosis using low-field MRI. Our study emphasizes the inflammatory and destructive character of the arthropathy besides the well-known degenerative joint changes described in conventional X-ray. The impact of joint changes in asymptomatic patients deserves further investigation.

Improved detection of synovial boundaries in ultrasound examination by using a cascade of active-contours

Rheumatoid arthritis (RA) is a chronic multisystemic autoimmune disease, with an unclear etiopathogenesis. Its early diagnosis and activity assessment are essential to adjust the proper therapy. Among the different imaging techniques, ultrasonography (US) allows direct visualization of early inflammatory joint changes as synovitis, being also rapidly performed and easily accepted by patients. We propose an algorithm to semi-automatically detect synovial boundaries on US images, requiring minimal user interaction. In order to identify the synovia-bone and the synovia-soft tissues interfaces, and to tackle the morphological variability of diseased joints, a cascade of two different active contours is developed, whose composition corresponds to the whole synovial boundary.The algorithm was tested on US images acquired from proximal interphalangeal (PIP) and metacarpophalangeal (MCP) finger joints of 34 subjects. The results have been compared with a consensus manual segmentation. We obtained an overall mean sensitivity of 85±13%, and a mean Dice's similarity index of 80±8%, with a mean Hausdorff distance from the manual segmentation of 28±10 pixels (approximately 1.4±0.5mm), that are a better performance than those obtained by the raters with respect to the consensus.

EXPERIENCE OF ADALIMUMAB TREATMENT IN PATIENT WITH JUVENILE ANKYLOSING SPONDYLITIS AND UVEITIS

научный биометрический журнал, который знакомит читателя с клиническими рекомендациями и особенностями применения лекарственных и вакцинных средств у детей, предоставляет исчерпывающую информацию о воздействии лекарственных средств на плод, о проводимых в

MRI quantification of rheumatoid arthritis: Current knowledge and future perspectives

The international consensus on treatment of rheumatoid arthritis (RA) involves early initiation of disease modifying anti-rheumatic drugs (DMARDs) for which a reliable identification of early disease is mandatory. Conventional radiography of the joints is considered the standard method for detecting and quantifying joint damage in RA. However, radiographs only show late disease manifestations as joint space narrowing and bone erosions, whereas it cannot detect synovitis and bone marrow oedema, i.e., inflammation in the synovium or the bone, which may be visualized by magnetic resonance imaging (MRI) months to years before erosions develop. Furthermore, MRI allows earlier visualization of bone erosions than radiography. In order to allow early treatment initiation and optimal guidance of the therapeutic strategy, there is a need for methods which are capable of early detection of inflammatory joint changes. In this review, we will discuss available data, advantages, limitations and potential future of MRI in RA.

Imaging in early-onset juvenile idiopathic arthritis: ultrasonography (US) and MRI favours conventional radiography in detecting early inflammatory changes in joints

Results Synovitis in affected joints was detected by US and MRI but not by X-ray. Conclusion US and MRI favours conventional radiography in detecting early inflammatory changes in smaller children with EO-JIA. Although detailed information is given by MRI, the use of MRI is limited to one anatomical region and the smaller children it cannot be performed without general anaesthesia. Thus, US seem most helpful in detecting early inflammatory changes in EO-JIA. from 15th Paediatric Rheumatology European Society (PreS) Congress London, UK. 14–17 September 2008

Skelettszintigraphie im Vergleich mit MRT und Sonographie beim Frühnachweis der Arthritis

Eine Arthritis des rheumatischen Formenkreises wird spezifisch an knöchernen Erosionen erkannt, die durch den charakteristischen Pannus hervorgerufen werden. In den Fingergelenken weist die dynamische Niedrig-Tesla-MRT Erosionen mit nahezu doppelter, aber nicht hundertprozentiger Sensitivität nach als die konventionelle Röntgendiagnostik, die Sonographie nimmt eine Mittelstellung ein. Beim Nachweis der wenig spezifischen Synovialitis und Tendovaginitis in den Fingergelenken sind die Mehrphasen-Skelettszintigraphie und die Sonographie gleichermaßen hochsensitiv, MRT ist deutlich unterlegen. Allerdings sagt die klassische Entzündungskonstellation in der Skelettszintigraphie - positive Befunde in der Früh- und Spätphase - nur etwas über die Entzündungsaktivität aus, die Sensitivität dieser Befundkonstellation ist erstaunlich gering. Vielmehr muss jeder Einzelbefund sowohl in der Früh- als auch Spätphase als positiv gewertet werden. Die Spezifität dieser Einzelbefunde ist trotzdem ausreichend hoch, Entzündungszeichen und auch Erosionen finden sich selbst mit MRT bei klinisch Gesunden. Nur mit der Zwei-Phasen-Skelettszintigraphie kann problemlos ein Ganzkörper-Gelenkstatus erstellt werden, der mit einem Höchstmaß an Sensitivität eine Synovialitis und/oder Tendovaginitis aufzeigen kann. Das Verfahren eignet sich deshalb besonders für die Ausschluss- aber auch für die Primärdiagnostik, eine Spezifizierung muss dann durch andere Verfahren (Bildgebung, Labor) erfolgen.

Assessment of Unspecific Near-Infrared Dyes in Laser-Induced Fluorescence Imaging of Experimental Arthritis

The aim of the study is to evaluate in vivo fluorescence imaging of experimental inflammatory joint disease by applying two different near-infrared (NIR) dyes in a model of Borrelia-induced Lyme arthritis. Forty mice, 20 with Lyme arthritis and 20 controls, were examined. Two nonspecific NIR carbocyanine dyes, indocyanine green (ICG) and a hydrophilic carbocyanine derivative (1,1'-bis-[4-sulfobutyl] indotricarbocyanine-5,5'-dicarboxylic acid diglucamide monosodium salt [SIDAG]), were administered intravenously at two doses. Fluorescence images were acquired before and during 120 seconds after injection of cyanine dyes. For both dyes, the area under the curve (AUC) was determined for the interval between 40 and 80 seconds after injection. In addition, the slope of the signal decrease was compared among animal groups. Results were compared with histological findings. The general temporal fluorescence intensity course for ICG was characterized by a rapid increase, with a peak at 40-50 seconds followed by a decrease; conversely for SIDAG, by a slow increase. AUC analysis for both dyes showed that the fluorescence signal differed significantly between controls and arthritic animals (P < .05). Within these groups, there were significant differences between the two doses investigated. ICG differed significantly between control and arthritic animals in the slope of the signal decrease for both doses investigated (P < .05). Histological examination showed early stages of inflammation in arthritic animals. NIR fluorescence imaging based on the pharmacokinetic behavior of ICG or SIDAG is a promising approach to detect inflammatory joint changes of experimental arthritis. Moreover, SIDAG is suited to differentiate inflammatory and noninflammatory joints 24 hours after dye application.