Menopause, postmenopausal hormone use and serum uric acid levels in US women – The Third National Health and Nutrition Examination Survey

Modern imaging modalities, including magnetic resonance imaging (MRI), are valuable diagnostic and therapy monitoring tools in rheumatoid arthritis (RA). This article reviewed how these imaging modalities have greatly improved our understanding of pathogenic mechanisms in RA, namely the link between inflammation and damage. For example, traditional paradigms regarding the mechanisms of joint destruction, including the idea that synovitis and damage are uncoupled, have been challenged. As the power of MRI increases, there is a need to define normality since apparently normal joints occasionally exhibit MRI evidence of synovitis in the absence of symptoms.     

MRI osteitis predicts cartilage damage at the wrist in RA: a three-year prospective 3T MRI study examining cartilage damage

Introduction

Cartilage damage impacts on patient disability in rheumatoid arthritis (RA). The aims of this magnetic resonance imaging (MRI) study were to investigate cartilage damage over three years and determine predictive factors.

Methods

A total of 38 RA patients and 22 controls were enrolled at t = 0 (2009). After 3 years, clinical and MRI data were available in 28 patients and 15 controls. 3T MRI scans were scored for cartilage damage, bone erosion, synovitis and osteitis. A model was developed to predict cartilage damage from baseline parameters.

Results

Inter-reader reliability for the Auckland MRI cartilage score (AMRICS) was high for status scores; intraclass correlation coefficient (ICC), 0.90 (0.81 to 0.95) and moderate for change scores (ICC 0.58 (0.24 to 0.77)). AMRICS scores correlated with the Outcome MEasures in Rheumatoid Arthritis Clinical Trials (OMERACT) MRI joint space narrowing (jsn) and X-Ray (XR) jsn scores (r =0.96, P < 0.0001 and 0.80, P < 0.0001, respectively). AMRICS change scores were greater for RA patients than controls (P = 0.06 and P = 0.04 for the two readers). Using linear regression, baseline MRI cartilage, synovitis and osteitis scores predicted the three-year AMRICS (R² = 0.67, 0.37 and 0.39, respectively). A multiple linear regression model predicted the three-year AMRICS (R² = 0.78). Baseline radial osteitis predicted increased cartilage scores at the radiolunate and radioscaphoid joints, P = 0.0001 and 0.0012, respectively and synovitis at radioulnar, radiocarpal and intercarpal-carpometacarpal joints also influenced three-year cartilage scores (P-values of 0.001, 0.04 and 0.01, respectively).

Conclusions

MRI cartilage damage progression is preceded by osteitis and synovitis but is most influenced by pre-existing cartilage damage suggesting primacy of the cartilage damage pathway in certain patients.     

Magnetic resonance imaging in psoriatic arthritis: a review of the literature

Psoriatic arthritis is a diverse condition that may be characterized by peripheral inflammatory arthritis, axial involvement, dactylitis and enthesitis. Magnetic resonance imaging (MRI) allows visualization of soft tissue, articular and entheseal lesions, and provides a unique picture of the disease process that cannot be gained using other imaging modalities. This review focuses on the literature on MRI in psoriatic arthritis published from 1996 to July 2005. The MRI features discussed include synovitis, tendonitis, dactylitis, bone oedema, bone erosions, soft tissue oedema, spondylitis/sacroiliitis and subclinical arthropathy. Comparisons have been drawn with the more extensive literature describing the MRI features of rheumatoid arthritis and ankylosing spondylitis.     

Dynamic contrast-enhanced magnetic resonance imaging of metacarpophalangeal joints reflects histological signs of synovitis in rheumatoid arthritis

Introduction

Synovial inflammation and joint destruction in rheumatoid arthritis (RA) may progress despite clinical remission. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is increasingly used to detect synovial inflammation in RA. Although small joints such as metacarpophalangeal (MCP) joints are mainly affected by RA, MRI findings have never been directly compared to histological synovitis in MCP synovial tissue. The objective of the current study was therefore to analyse if DCE-MRI relates to histological signs of synovitis small RA joints.

Methods

In 9 RA patients, DCE-MRI (3 Tesla, dynamic 2D T1 weighted turbo-flash sequence) of the hand was performed prior to arthroscopically-guided synovial biopsies from the second MCP of the imaged hand. Maximum enhancement (ME), rate of early enhancement, and maximum rate of enhancement were assessed in the MCP. Synovial biopsies were stained for determination of sublining CD68 and the Synovitis Score. Correlations between MRI and histological data were calculated according to Spearman.

Results

ME of the MCP significantly correlated to sublining CD68 staining (r = 0.750, P = 0.02), the Synovitis Score (r = 0.743, P = 0.02), and the subscores for lining layer hypertrophy (r = 0.789, P = 0.01) and cellular density (r = 0.842; P = 0.004).

Conclusions

Perfusion imaging of synovial tissue in RA finger joints employing DCE-MRI reflects histological synovial inflammation. According to our study, ME is the most closely associated parameter amongst the measures considered.     

VEGF and imaging of vessels in rheumatoid arthritis

Angiogenesis is a prominent feature of rheumatoid synovitis. Formation of new blood vessels permits a supply of nutrients and oxygen to the augmented inflammatory cell mass and so contributes to perpetuation of joint disease. Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific growth factor that is upregulated by proinflammatory cytokines and by hypoxia. Serum VEGF concentrations are elevated in rheumatoid arthritis (RA) and correlate with disease activity. Furthermore, serum VEGF measured at first presentation in RA is highly significantly correlated with radiographic progression of disease over the subsequent year. Power Doppler ultrasonography is a sensitive method for demonstrating the presence of blood flow in small vessels and there is a very close relation between the presence or absence of vascular flow signal on power Doppler imaging and the rate of early synovial enhancement on dynamic gadolinium-enhanced magnetic resonance imaging (MRI) of joints with RA. Images obtained by both dynamic enhanced MRI and power Doppler ultrasonography correlate with vascularity of synovial tissue as assessed histologically. In early RA, there is a striking association between joint erosions assessed on high-resolution ultrasonography and vascular signal in power Doppler mode. Collectively, these findings implicate vascular pannus in the erosive phase of disease and strongly suggest that proangiogenic molecules such as VEGF are targets for novel therapies in RA. Animal model data supports this concept. It seems likely that serological and imaging measures of vascularity in RA will become useful tools in the assessment of disease activity and response to therapy.     

Dynamic magnetic resonance of the wrist in psoriatic arthritis reveals imaging patterns similar to those of rheumatoid arthritis

This dynamic magnetic resonance imaging (MRI) study is concerned with a prospective evaluation of wrist synovitis in patients with psoriatic arthritis (PsA) in comparison with patients with rheumatoid arthritis (RA) and healthy controls. Fifteen consecutive patients with PsA, 49 consecutive patients with RA, 30 RA patients matched for disease severity with those with PsA, and 8 healthy controls were studied. MRI was performed with a low-field (0.2T), extremity-dedicated machine. After an intravenous bolus injection of gadolinium-diethylenetriaminepentaacetic acid, 20 consecutive fast spin-echo axial images of the wrist were obtained every 18 s. The enhancement ratio was calculated both as rate of early enhancement (REE), which shows the slope of the curve of contrast uptake per second during the first 55 s, and as relative enhancement (RE), which indicates the steady state of enhancement. The REE was 1.0 ± 0.6 in patients with PsA, 1.6 ± 0.7 in consecutive patients with RA, and 0.1 ± 0.1 in controls (p <0.001). The RE was 87.1 ± 39.2 in patients with PsA, 125.8 ± 48.0 in consecutive RA patients, and 15.5 ± 19.2 in controls (p <0.001). However, the same figures in matched RA patients were 1.3 ± 0.7 and 107.3 ± 48.2, respectively (not significant in comparison with PsA). Rheumatoid-like PsA and oligoarticular PsA did not differ from each other in terms of synovial enhancement. Dynamic MRI shows the same pattern of synovitis in patients with PsA and RA when the two groups are matched for disease severity. This technique cannot be used to differentiate PsA from RA. However, REE and RE were significantly higher in PsA than in normal controls, with only one instance of overlap between values found for the two groups.     

类风湿性关节炎活动性病变MRI征象及其与FIB、FDP、D-D的相关性研究

摘要 目的：探讨类风湿性关节炎（RA）活动性病变磁共振成像（MRI）征象及其与纤维蛋白原（FIB）、纤维蛋白(原)降解产物（FDP）、D-二聚体（D-D）的相关性研究。方法：选取2020年1月-2021年2月期间我院诊治的61例RA患者,根据28个关节疾病活动指数（DAS28）评分将其分为活动组（35例）和稳定组（26例）。对比两组MRI征象,血清FIB、FDP、D-D水平。采用Spearman相关性分析RA活动期患者MRI各征象间的相关性及MRI各征象与血清FIB、FDP、D-D水平间的相关性。结果：活动组滑膜增厚或滑膜炎、骨髓水肿、软骨及骨侵蚀、腱鞘炎或周围软组织受累、关节腔积液征象人数占比均高于稳定组（P＜0.05）。活动组患者血清FIB、FDP、D-D水平均高于稳定组（P＜0.05）。Spearman相关性分析结果显示,RA活动期患者滑膜增厚或滑膜炎征象与骨髓水肿、软骨及骨侵蚀、关节腔积液征象均呈正相关（P＜0.05）,骨髓水肿征象与软骨及骨侵蚀征象呈正相关（P＜0.05）;RA活动期患者滑膜增厚或滑膜炎、骨髓水肿、关节腔积液征象与血清FIB、FDP、D-D水平均呈正相关（P＜0.05）,软骨及骨侵蚀征象与FIB呈正相关（P＜0.05）。结论：MRI征象可清晰显示RA患者的滑膜、骨质、关节腔及周围肌腱、软组织等异常改变,且MRI征象之间具有相关性,可在一定程度上反映RA的病理改变;血清FIB、FDP、D-D的检测有助于反映RA活动情况;MRI征象与血清FIB、FDP、D-D水平间具有相关性,二者联合应用有助于进一步评估RA活动情况。     

Subclinical inflammation on MRI of hand and foot of anticitrullinated peptide antibody–negative arthralgia patients at risk for rheumatoid arthritis

Introduction

It is known that anticitrullinated peptide antibody (ACPA)–positive rheumatoid arthritis (RA) has a preclinical phase. Whether this phase is also present in ACPA-negative RA is unknown. To determine this, we studied ACPA-negative arthralgia patients who were considered prone to progress to RA for local subclinical inflammation observed on hand and foot magnetic resonance imaging (MRI) scans.

Methods

We studied a total of 64 ACPA-negative patients without clinically detectable arthritis and with arthralgia of the small joints within the previous 1 year. Because of the character of the patients’ symptoms, the rheumatologists considered these patients to be prone to progress to RA. For comparisons, we evaluated 19 healthy, symptom-free controls and 20 ACPA-negative RA patients, who were identified according to the 1987 American Rheumatism Association criteria. All participants underwent MRI of unilateral wrist, metacarpophalangeal and metatarsophalangeal joints. Synovitis and bone marrow oedema (BME) were scored according to the OMERACT rheumatoid arthritis magnetic resonance imaging scoring system, and the scores were summed to yield the ‘MRI inflammation score’. Scores were compared between groups. Among the ACPA-negative arthralgia patients, MRI inflammation scores were related to C-reactive protein (CRP) levels and the tenderness of scanned joints.

Results

MRI inflammation scores increased progressively among the groups of controls and ACPA-negative arthralgia and RA patients (median scores = 0, 1 and 10, respectively; P < 0.001). The MRI inflammation scores of ACPA-negative arthralgia patients were significantly higher than those of controls (P = 0.018). In particular, the synovitis scores were higher in ACPA-negative arthralgia patients (P = 0.046). Among the ACPA-negative arthralgia patients, inflammation was observed predominantly in the wrist (53%). The synovitis scores were associated with CRP levels (P = 0.007) and joint tenderness (P = 0.026). Despite the limited follow-up duration, five patients developed clinically detectable arthritis. These five patients had higher scores for MRI inflammation (P = 0.001), synovitis (P = 0.002) and BME (P = 0.003) compared to the other patients.

Conclusion

Subclinical synovitis was observed in the small joints of ACPA-negative arthralgia patients, and especially in patients whose conditions progressed to clinically detectable arthritis. This finding suggests the presence of a preclinical phase in ACPA-negative RA. Further longitudinal studies of these lesions and patients are required to confirm this hypothesis.     

Synovial explant inflammatory mediator production corresponds to rheumatoid arthritis imaging hallmarks: a cross-sectional study

Introduction

Despite the widespread use of magnetic resonance imaging (MRI) and Doppler ultrasound for the detection of rheumatoid arthritis (RA) disease activity, little is known regarding the association of imaging-detected activity and synovial pathology. The purpose of this study was to compare site-specific release of inflammatory mediators and evaluate the corresponding anatomical sites by examining colour Doppler ultrasound (CDUS) and MRI scans.

Methods

RA patients were evaluated on the basis of CDUS and 3-T MRI scans and subsequently underwent synovectomy using a needle arthroscopic procedure of the hand joints. The synovial tissue specimens were incubated for 72 hours, and spontaneous release of monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), macrophage inflammatory protein 1β (MIP-1β) and IL-8 was measured by performing multiplex immunoassays. Bone marrow oedema (BME), synovitis and erosion scores were estimated on the basis of the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Mixed models were used for the statistical analyses. Parsimony was achieved by omitting covariates with P > 0.1 from the statistical model.

Results

Tissue samples from 58 synovial sites were obtained from 25 patients. MCP-1 was associated with CDUS activity (P = 0.009, approximate Spearman’s ρ = 0.41), RAMRIS BME score (P = 0.01, approximate Spearman’s ρ = 0.42) and RAMRIS erosion score (P = 0.03, approximate Spearman’s ρ = 0.31). IL-6 was associated with RAMRIS synovitis score (P = 0.04, approximate Spearman’s ρ = 0.50), BME score (P = 0.04, approximate Spearman’s ρ = 0.31) and RAMRIS erosion score (P = 0.03, approximate Spearman’s ρ = 0.35). MIP-1β was associated with CDUS activity (P = 0.02, approximate Spearman’s ρ = 0.38) and RAMRIS synovitis scores (P = 0.02, approximate Spearman’s ρ = 0.63). IL-8 associations with imaging outcome measures did not reach statistical significance.

Conclusions

The association between imaging activity and synovial inflammatory mediators underscores the high sensitivity of CDUS and MRI in the evaluation of RA disease activity. The associations found in our present study have different implications for synovial mediator releases and corresponding imaging signs. For example, MCP-1 and IL-6 were associated with both general inflammation and bone destruction, in contrast to MIP-1β, which was involved solely in general synovitis. The lack of association of IL-8 with synovitis was likely underestimated because of a large proportion of samples above assay detection limits among the patients with the highest synovitis scores.     

Inflammatory lesions in the bone marrow of rheumatoid arthritis patients: a morphological perspective

The synovial tissue stands at the epicenter of joint pathology in rheumatoid arthritis (RA). As a primary target of the disease, studies on the synovium have provided invaluable insights into the mechanisms involved in disease pathogenesis. Recent work has, however, revealed the importance of a previously unseen anatomic compartment in direct contact with the joint space, namely the subchondral bone marrow. Bone marrow edema (BME) visible on magnetic resonance imaging (MRI) is clinically meaningful in both early and late RA as it associates with future development of bone erosions and poor functional outcomes. Although the histopathologic correlates of MRI-based BME in early RA remain obscure, studies in advanced disease are consistent in describing lymphocytic inflammatory infiltrates within the subchondral marrow cavity of affected joints. In this review, we discuss the nature of bone marrow lesions in patients with RA, analyze their relationship with synovitis, and explore their potential contribution to the pathological processes of the disease.Rheumatoid arthritis (RA) is traditionally regarded as an archetypal disease of the synovial tissue. The synovial membrane indeed undergoes early inflammatory changes, which include increased vascularity as well as intimal lining layer hyperplasia and accumulation of macrophages, plasma cells, T cells, B cells, dendritic cells, natural killer cells and mast cells in the sublining, among other changes [1]. Collectively, localization of inflammation to the synovium is primarily responsible for the dysregulated cellular and molecular mechanisms that ultimately lead to the typical signs and symptoms of RA, including joint pain, stiffness, swelling and structural changes. Although the pathogenic and clinical importance of synovitis is beyond question, it is becoming increasingly apparent that a ''synovio-centric'' model of RA could be limiting. Indeed, other anatomic compartments appear to be involved at all stages of the disease. The most important example comes from the recognition that clinical arthritis and subclinical synovitis are anticipated by a pre-articular immunologic phase possibly developing in lymphoid tissues as well as in the lungs [2,3]. Full-blown joint disease itself spreads well beyond synovial tissue inflammation. Established arthritis can be characterized by the involvement of at least two other compartments that are in direct contact with the joint space. These include the draining lymph nodes (LNs) [4,5] and, of special relevance, the subchondral bone marrow (BM) [6].As dysregulated B cell responses are central pathogenic events in RA and B-cell autoreactivity originates, at least in part, from defective checkpoints within the BM (a primary lymphoid organ) [7], the role of this compartment in the immunopathogenesis of RA has attracted great attention over the years. Data supporting the existence of BM abnormalities were mainly derived from studies on marrow aspirates/biopsies from the sternum and the iliac crest, which are primary hematopoietic and immunologic sites in adult life. The role that the ''red marrow'' might play in the immunologic disturbances of RA thus appears interesting but not completely unexpected. Less predictably, evidence has accumulated supporting the additional involvement of the BM adjacent to inflamed joints at peripheral sites. This is normally a fat-rich tissue (''yellow marrow'') where hematopoiesis is not prominent. In RA, the fat can be replaced by a vascularized, cell-rich inflammatory tissue. Combined with imaging data coming from magnetic resonance imaging (MRI) studies, histopathologic changes described within the subchondral BM have been postulated to be intimately involved in the pathological processes producing local inflammation and tissue remodeling in RA joints [6,8-10]. Here we will discuss the most relevant findings related to BM alterations in RA, focusing on their morphological characteristics and pathologic significance. In view of the clinical relevance of MRI findings, special emphasis is given to the subchondral BM.     

Imaging modalities in hand osteoarthritis - status and perspectives of conventional radiography, magnetic resonance imaging, and ultrasonography

Hand osteoarthritis (OA) is very frequent in middle-aged and older women and men in the general population. Currently, owing to high feasibility and low costs, conventional radiography (CR) is the method of choice for evaluation of hand OA. CR provides a two-dimensional picture of bony changes, such as osteophytes, erosions, cysts, and sclerosis, and joint space narrowing as an indirect measure of cartilage loss. There are several standardized scoring methods for evaluation of radiographic hand OA. The scales have shown similar reliability, validity, and sensitivity to change, and no conclusion about the preferred instrument has been drawn. Patients with hand OA may experience pain, stiffness, and physical disability, but the associations between radiographic findings and clinical symptoms are weak to moderate and vary across studies. OA is, indeed, recognized to involve the whole joint, and modern imaging techniques such as ultrasound (US) and magnetic resonance imaging (MRI) could be valuable tools for better evaluation of hand OA. Standardized scoring methods have been proposed for both modalities. Several studies have examined the validity of US features in hand OA, whereas knowledge of the validity of MRI is more limited. However, both synovitis (detected by either US or MRI) and MRI-defined bone marrow lesions have been associated with pain, indicating that treatment of inflammation is important for pain management in hand OA. Both US and MRI have shown better sensitivity than CR in detection of erosions, and this may indicate that erosive hand OA may be more common than previously thought.     

Imaging modalities in hand osteoarthritis--and perspectives of conventional radiography, magnetic resonance imaging, and ultrasonography

Hand osteoarthritis (OA) is very frequent in middle-aged and older women and men in the general population. Currently, owing to high feasibility and low costs, conventional radiography (CR) is the method of choice for evaluation of hand OA. CR provides a two-dimensional picture of bony changes, such as osteophytes, erosions, cysts, and sclerosis, and joint space narrowing as an indirect measure of cartilage loss. There are several standardized scoring methods for evaluation of radiographic hand OA. The scales have shown similar reliability, validity, and sensitivity to change, and no conclusion about the preferred instrument has been drawn. Patients with hand OA may experience pain, stiffness, and physical disability, but the associations between radiographic findings and clinical symptoms are weak to moderate and vary across studies. OA is, indeed, recognized to involve the whole joint, and modern imaging techniques such as ultrasound (US) and magnetic resonance imaging (MRI) could be valuable tools for better evaluation of hand OA. Standardized scoring methods have been proposed for both modalities. Several studies have examined the validity of US features in hand OA, whereas knowledge of the validity of MRI is more limited. However, both synovitis (detected by either US or MRI) and MRI-defined bone marrow lesions have been associated with pain, indicating that treatment of inflammation is important for pain management in hand OA. Both US and MRI have shown better sensitivity than CR in detection of erosions, and this may indicate that erosive hand OA may be more common than previously thought.     

Bone marrow edema and osteitis in rheumatoid arthritis: the imaging perspective

Magnetic resonance imaging bone marrow edema is an imaging feature that has been described in many conditions, including osteomyelitis, overuse syndromes, avascular necrosis, trauma, and inflammatory arthritides. In rheumatoid arthritis (RA), bone edema has special significance as it has been shown to be a common and widespread lesion that is often apparent at the hands and wrists but has also been described elsewhere, including the feet. It may occur in early or late disease and has been shown in several large cohort studies to have major negative implications for prognosis. It is the strongest predictor of erosive progression yet to be identified and characteristically occurs in those patients with the most aggressive and potentially disabling disease. In patients with undifferentiated arthritis, bone edema also predicts progression to criteria-positive RA, both independently and to a greater extent when combined with anti-cyclic citrullinated peptide status or rheumatoid factor positivity. Its histological correlate in the late stages of RA has been shown to be osteitis, in which the bone marrow beneath the joint is invaded by an inflammatory and vascular lymphoplasmacytic infiltrate. This lies adjacent to trabecular bone, where increased numbers of osteoclasts have been observed within resorption lacunae, suggesting a mechanistic link between inflammation and erosive bone damage. This could lead to erosion both of the overlying cortex, leading to classic radiographic rheumatoid erosions, and of local trabecular bone, possibly contributing to periarticular osteopenia and cyst formation. In addition to synovitis, osteitis is now regarded as a major rheumatoid lesion that is responsive to therapeutic intervention.     

Three Groups in the 28 Joints for Rheumatoid Arthritis Synovitis – Analysis Using More than 17,000 Assessments in the KURAMA Database

Rheumatoid arthritis (RA) is a joint-destructive autoimmune disease. Three composite indices evaluating the same 28 joints are commonly used for the evaluation of RA activity. However, the relationship between, and the frequency of, the joint involvements are still not fully understood. Here, we obtained and analyzed 17,311 assessments for 28 joints in 1,314 patients with RA from 2005 to 2011 from electronic clinical chart templates stored in the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Affected rates for swelling and tenderness were assessed for each of the 28 joints and compared between two different sets of RA patients. Correlations of joint symptoms were analyzed for swellings and tenderness using kappa coefficient and eigen vectors by principal component analysis. As a result, we found that joint affected rates greatly varied from joint to joint both for tenderness and swelling for the two sets. Right wrist joint is the most affected joint of the 28 joints. Tenderness and swellings are well correlated in the same joints except for the shoulder joints. Patients with RA tended to demonstrate right-dominant joint involvement and joint destruction. We also found that RA synovitis could be classified into three categories of joints in the correlation analyses: large joints with wrist joints, PIP joints, and MCP joints. Clustering analysis based on distribution of synovitis revealed that patients with RA could be classified into six subgroups. We confirmed the symmetric joint involvement in RA. Our results suggested that RA synovitis can be classified into subgroups and that several different mechanisms may underlie the pathophysiology in RA synovitis.     

Promising techniques for breast cancer detection,diagnosis, and staging using non-ionizing radiation imaging techniques

Traditional imaging for the diagnosis and staging of breast cancer has relied on the tissue morphology of cancers in the background of normal patterns of fibroglandular breast tissue. X-ray mammography and ultrasound have been the primary modalities for the diagnosis and the work-up of breast cancer. New modalities have been validated including magnetic resonance imaging (MRI) and positron emission tomography (PET). New pulse sequences in MRI combined with contrast enhancement kinetic perfusion curves have greatly enhanced detection of mammographically occult cancers. New modalities on the horizon include optical imaging, exploiting again the differential perfusion properties of cancers in a background of normal glandular tissue. Even more specificity can be ach eved with the addition of ductal or intravenous introduction of optical probes specific to tumor associated antigens such as the HER-2/neu receptor in aggressive breast cancers. Quantum dots and other fluorescent dyes coupled to peptides or other probes will greatly enhance our ability to detect cancers earlier and without ionizing radiation.     

Quantitative assessment of synovitis in patients with rheumatoid arthritis using fluorescence optical imaging

Introduction

To prospectively evaluate quantitative assessment of fluorescence optical imaging (FOI) for differentiation of synovitic from non-synovitic joints in patients suffering from rheumatoid arthritis (RA).

Methods

FOI of the hands was performed in patients with active RA, and a stratified quantitative fluorescence readout (FLRO) of 3 phases (1-120 s; 121-240 s; 241-360 s) was generated for 5 individual joints of the clinical predominant hand (carpal joint, metacarpophalangeal and proximal interphalangeal joints of digits II & III). To dissect the effect of the overall perfusion of the hand from the perfusion due to synovitis, a fluorescence ratio (FLRA) was additionally calculated, dividing each FLRO by the readout of the eponychium of digit II. The mean FLRO and FLRA were compared between joints with absent vs. present synovitis determined by clinical examination, grayscale, color Doppler ultrasonography, or magnetic resonance imaging (MRI).

Results

The analysis for 90 individual joints from 18 patients yielded FLRO ranging from 4.4 to 49.0 × 10³, and FLRAs ranging from 0.37 to 2.27. Overall, the analyses based on the FLRA revealed a higher discrimination than the analyses related to the FLRO, demonstrating most significant differences in phases 2 and 3. A sensitivity of 26/39 (67%) and a specificity of 31/40 (77%) were calculated for FLRA of phase 3 using a cut-off value of more than 1.2 to detect MRI-confirmed synovitis with FOI.

Conclusions

FOI has a potential for visualizing synovitis in subjects with RA. For adequate FOI interpretation, quantitative analysis should be based on the novel FLRA calculated for phases 2 and 3.     

Physiotherapy in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic and painful clinical condition that leads to progressive joint damage, disability, deterioration in quality of life, and shortened life expectancy. Even mild inflammation may result in irreversible damage and permanent disability. The clinical course according to symptoms may be either intermittent or progressive in patients with RA. In most patients, the clinical course is progressive, and structural damage develops in the first 2 years. The aim of RA management is to achieve pain relief and prevent joint damage and functional loss. Physiotherapy and rehabilitation applications significantly augment medical therapy by improving the management of RA and reducing handicaps in daily living for patients with RA. In this review, the application of physiotherapy modalities is examined, including the use of cold/heat applications, electrical stimulation, and hydrotherapy. Rehabilitation treatment techniques for patients with RA such as joint protection strategies, massage, exercise, and patient education are also presented.     

Expanding the armamentarium for the spondyloarthropathies

Ankylosing spondylitis (AS) is a member of the family of spondyloarthropathies, which are inflammatory arthritides largely involving the axial skeleton and commonly accompanied by peripheral arthritis. Genetic factors, particularly the presence of HLA-B27, are major contributors to the susceptibility for AS. Despite some therapeutic advances, the treatment options for patients with AS and related disorders have been limited. Several lines of evidence have led to the hypothesis that patients with AS might benefit from treatment with tumor necrosis factor (TNF). Specifically, TNF concentrations are known to be significantly elevated in the synovium of patients with rheumatoid arthritis (RA), in the inflamed gut of patients with inflammatory bowel disease, and in the inflamed sacroiliac joints of patients with AS. The anti-TNF agents have been shown to be of benefit in, and currently have indications for, RA (etanercept, infliximab, adalimumab), Crohn's disease (infliximab), and psoriatic arthritis (etanercept). Because the spondyloarthropathies share pathogenetic mechanisms with the above-specified disease states, studies have been conducted to evaluate the effectiveness of anti-TNF agents in several disorders, including AS. Data from clinical trials so far with infliximab and etanercept show that patients with AS and related disorders achieve significant improvement in clinical signs and symptoms based on validated outcomes measures. Computed tomography and magnetic resonance imaging (MRI) can facilitate the early diagnosis of AS. Studies with infliximab using MRI together with updated scoring methods demonstrated significant decreases in associated spinal inflammation. TNF antagonist therapy is well tolerated in patients with AS, with a side effect profile consistent with the prior experience of patients with RA.     

Biofunctionalized Prussian Blue Nanoparticles for Multimodal Molecular Imaging Applications

Multimodal, molecular imaging allows the visualization of biological processes at cellular, subcellular, and molecular-level resolutions using multiple, complementary imaging techniques. These imaging agents facilitate the real-time assessment of pathways and mechanisms in vivo, which enhance both diagnostic and therapeutic efficacy. This article presents the protocol for the synthesis of biofunctionalized Prussian blue nanoparticles (PB NPs) - a novel class of agents for use in multimodal, molecular imaging applications. The imaging modalities incorporated in the nanoparticles, fluorescence imaging and magnetic resonance imaging (MRI), have complementary features. The PB NPs possess a core-shell design where gadolinium and manganese ions incorporated within the interstitial spaces of the PB lattice generate MRI contrast, both in T₁ and T₂-weighted sequences. The PB NPs are coated with fluorescent avidin using electrostatic self-assembly, which enables fluorescence imaging. The avidin-coated nanoparticles are modified with biotinylated ligands that confer molecular targeting capabilities to the nanoparticles. The stability and toxicity of the nanoparticles are measured, as well as their MRI relaxivities. The multimodal, molecular imaging capabilities of these biofunctionalized PB NPs are then demonstrated by using them for fluorescence imaging and molecular MRI in vitro.     

Towards omni-tomography--grand fusion of multiple modalities for simultaneous interior tomography

We recently elevated interior tomography from its origin in computed tomography (CT) to a general tomographic principle, and proved its validity for other tomographic modalities including SPECT, MRI, and others. Here we propose "omni-tomography", a novel concept for the grand fusion of multiple tomographic modalities for simultaneous data acquisition in a region of interest (ROI). Omni-tomography can be instrumental when physiological processes under investigation are multi-dimensional, multi-scale, multi-temporal and multi-parametric. Both preclinical and clinical studies now depend on in vivo tomography, often requiring separate evaluations by different imaging modalities. Over the past decade, two approaches have been used for multimodality fusion: Software based image registration and hybrid scanners such as PET-CT, PET-MRI, and SPECT-CT among others. While there are intrinsic limitations with both approaches, the main obstacle to the seamless fusion of multiple imaging modalities has been the bulkiness of each individual imager and the conflict of their physical (especially spatial) requirements. To address this challenge, omni-tomography is now unveiled as an emerging direction for biomedical imaging and systems biomedicine.