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Chronic musculoskeletal pain is among the most highly prevalent diseases worldwide. Managing patients with chronic pain remains very challenging because current imaging techniques focus on morphological causes of pain that can be inaccurate and misleading. Moving away from anatomical constructs of disease, molecular imaging has emerged as a method to identify diseases according to their molecular, physiologic, or cellular signatures that can be applied to the variety of biomolecular changes that occur in nociception and pain processing and therefore have tremendous potential for precisely pinpointing the source of a patient's pain. Several molecular imaging approaches to image the painful process are now available, including imaging of voltage-gated sodium channels, calcium channels, hypermetabolic processes, the substance P receptor, the sigma-1 receptor, and imaging of macrophage trafficking. This article provides an overview of promising molecular imaging approaches for the imaging of musculoskeletal pain with a focus on preclinical methods. [ABSTRACT FROM AUTHOR]

Objective: Infrapatellar fat pad (IPFP) fat-suppressed T2 (T2FS) hyperintense regions on MRI are an important imaging feature of knee osteoarthritis (OA) and are thought to represent inflammation. These regions are also common in non-OA subjects, and may not always be linked to inflammation. Our aim was to evaluate quantitative blood perfusion parameters, as surrogate measure of inflammation, within T2FS-hyperintense regions in patients with OA, with patellofemoral pain (PFP) (supposed OA precursor), and control subjects.Methods: Twenty-two knee OA patients, 35 PFP patients and 43 healthy controls were included and underwent MRI, comprising T2 and DCE-MRI sequences. T2FS-hyperintense IPFP regions were delineated and a reference region was drawn in adjacent IPFP tissue with normal signal intensity. After fitting the extended Tofts pharmacokinetic model, quantitative DCE-MRI perfusion parameters were compared between the two regions within subjects in each subgroup, using a paired Wilcoxon signed-rank test.Results: T2FS-hyperintense IPFP regions were present in 16 of 22 (73%) OA patients, 13 of 35 (37%) PFP patients, and 14 of 43 (33%) controls. DCE-MRI perfusion parameters were significantly different between regions with and without a T2FS-hyperintense signal in OA patients, demonstrating higher Ktrans compared to normal IFPF tissue (0.039 min-1 versus 0.025 min-1, p = 0.017) and higher Ve (0.157 versus 0.119, p = 0.010). For PFP patients and controls no significant differences were found.Conclusions: IPFP T2FS-hyperintense regions are associated with higher perfusion in knee OA patients in contrast to identically appearing regions in PFP patients and controls, pointing towards an inflammatory pathogenesis in OA only.Key Points: • Morphologically identical appearing T2FS-hyperintense infrapatellar fat pad regions show different perfusion in healthy subjects, subjects with patellofemoral pain, and subjects with knee osteoarthritis. • Elevated DCE-MRI perfusion parameters within T2FS-hyperintense infrapatellar fat pad regions in patients with osteoarthritis suggest an inflammatory pathogenesis in osteoarthritis, but not in patellofemoral pain and healthy subjects. [ABSTRACT FROM AUTHOR]

Objective. It has been suggested that repeated overload might sensitize nociceptors, causing local hyperalgesia in patients with patellofemoral pain (PFP). This might also lead to generalized hyperalgesia, indicative of altered central pain processing. This study aimed to investigate differences in pressure pain threshold (PPT) as a measure of pressure hyperalgesia between patients with PFP and healthy controls and in predefined subgroups and to study associations between PPTand patient characteristics. Design. Case-control study. Setting. Physiotherapy, general practices, and sports medicine practices. Subjects. Sixty-four patients with PFP and 70 healthy controls. Methods. Demographics, pain (numerical rating score), and function (anterior knee pain score) were obtained by questionnaire. The PPTwas measured with a handheld dynamometer with algometry tip at the most painful spot of the affected knee (medial facet in controls), the same spot at the contralateral knee, and at the contralateral forearm. Differences between groups were tested using analysis of variance techniques including the variables age, gender, body mass index, and sports participation. Results. Patients had significantly lower PPTs compared with controls at all locations (affected knee: mean difference 5 -12.2, 95% confidence interval [CI] 5 -17.3 to -7.1; contralateral knee: mean difference 5 -4.7, 95% CI 5 -10.1 to 0.52; contralateral arm: mean difference 5 -5.7, 95% CI 5 -10.5 to -0.8). Both male and female patients demonstrated lower PPTs, though a significant subgroup effect was found for female gender (effect size ranging from 0.73 to 0.98). Conclusions. Local and generalized pressure hyperalgesia, suggesting alterations in both peripheral and central pain processing, were present in patients with PFP, though females with PFP were most likely to suffer from generalized hyperalgesia. [ABSTRACT FROM AUTHOR]

Background: Structural abnormalities of the patellofemoral joint might play a role in the pathogenesis of patellofemoral pain (PFP), a common knee problem among young and physically active individuals. No previous study has investigated if PFP is associated with structural abnormalities of the patellofemoral joint using high-resolution magnetic resonance imaging (MRI). Purpose: To investigate the presence of structural abnormalities of the patellofemoral joint on high-resolution MRI in patients with PFP compared with healthy control subjects. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients with PFP and healthy control subjects between 14 and 40 years of age underwent high-resolution 3-T MRI. All images were scored using the Magnetic Resonance Imaging Osteoarthritis Knee Score with the addition of specific patellofemoral features. Associations between PFP and the presence of structural abnormalities were analyzed using logistic regression analyses adjusted for age, body mass index (BMI), sex, and sports participation. Results: A total of 64 patients and 70 control subjects were included in the study. Mean ± SD age was 23.2 ± 6.4 years, mean BMI ± SD was 22.9 ± 3.4 kg/m2, and 56.7% were female. Full-thickness cartilage loss was not present. Minor patellar cartilage defects, patellar bone marrow lesions, and high signal intensity of the Hoffa fat pad were frequently seen in both patients (23%, 53%, and 58%, respectively) and control subjects (21%, 51%, and 51%, respectively). After adjustment for age, BMI, sex, and sports participation, none of the structural abnormalities were statistically significantly associated with PFP. Conclusion: Structural abnormalities of the patellofemoral joint have been hypothesized as a factor in the pathogenesis of PFP, but the study findings suggest that structural abnormalities of the patellofemoral joint on MRI are not associated with PFP. [ABSTRACT FROM AUTHOR]

Background: Retropatellar cartilage damage has been suggested as an etiological factor for patellofemoral pain (PFP), a common knee condition among young and physically active individuals. To date, there is no conclusive evidence for an association between cartilage defects and PFP. Nowadays, advanced quantitative magnetic resonance imaging (MRI) techniques enable estimation of cartilage composition. Purpose: To investigate differences in patellofemoral cartilage composition between patients with PFP and healthy control subjects using quantitative MRI. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients with PFP and healthy control subjects underwent 3.0-T MRI including delayed gadolinium-enhanced MRI of cartilage and T1ρ and T2 mapping. Differences in relaxation times of patellofemoral cartilage were compared between groups by linear regression analyses, adjusted for age, body mass index, sex, sports participation, and time of image acquisition. Results: This case-control study included 64 patients and 70 controls. The mean (±SD) age was 23.2 ± 6.4 years and the mean body mass index was 22.9 ± 3.4 kg/m2; 56.7% were female. For delayed gadolinium-enhanced MRI of cartilage, the mean T1GD relaxation times of patellar (657.8 vs 669.4 ms) and femoral cartilage (661.6 vs 659.8 ms) did not significantly differ between patients and controls. In addition, no significant difference was found in mean T1ρ relaxation times of patellar (46.9 vs 46.0 ms) and femoral cartilage (50.8 vs 50.2 ms) and mean T2 relaxation times of patellar (33.2 vs 32.9 ms) and femoral cartilage (36.7 vs 36.6 ms) between patients and controls. Analysis of prespecified medial and lateral subregions within the patellofemoral cartilage also revealed no significant differences. Conclusion: There was no difference in composition of the patellofemoral cartilage, estimated with multiple quantitative MRI techniques, between patients with PFP and healthy control subjects. However, clinically relevant differences could not be ruled out for T1ρ in the adolescent population. Retropatellar cartilage damage has long been hypothesized as an important factor in the pathogenesis of PFP, but study findings suggest that diminished patellofemoral cartilage composition is not associated with PFP. [ABSTRACT FROM AUTHOR]

Chronic knee pain is a common condition. Causes of knee pain include trauma, inflammation, and degeneration, but in many patients the pathophysiology remains unknown. Recent developments in advanced magnetic resonance imaging (MRI) techniques and molecular imaging facilitate more in-depth research focused on the pathophysiology of chronic musculoskeletal pain and more specifically inflammation. The forthcoming new insights can help develop better targeted treatment, and some imaging techniques may even serve as imaging biomarkers for predicting and assessing treatment response in the future. This review highlights the latest developments in perfusion MRI, diffusion MRI, and molecular imaging with positron emission tomography/MRI and their application in the painful knee. The primary focus is synovial inflammation, also known as synovitis. Bone perfusion and bone metabolism are also addressed. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is among the top 10 burdensome diseases, with the knee the most affected joint. Magnetic resonance imaging (MRI) allows whole-knee assessment, making it ideally suited for imaging OA, considered a multitissue disease. Three-dimensional (3D) MRI enables the comprehensive assessment of OA, including quantitative morphometry of various joint tissues. Manual tissue segmentation on 3D MRI is challenging but may be overcome by advanced automated image analysis methods including artificial intelligence (AI). This review presents examples of the utility of 3D MRI for knee OA, focusing on the articular cartilage, bone, meniscus, synovium, and infrapatellar fat pad, and it highlights several applications of AI that facilitate segmentation, lesion detection, and disease classification. [ABSTRACT FROM AUTHOR]

Background: Patellofemoral malalignment has been observed among people with patellofemoral pain (PFP) and may be associated with the presence of imaging features of osteoarthritis, symptoms, and function. Purpose: To determine whether patellofemoral joint alignment and bony shape are associated with (1) cartilage, bone, and soft tissue morphological abnormalities defined on magnetic resonance imaging (MRI) and (2) reported symptoms and function among people with PFP. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Participants (mean 6 SD age, 30.2 6 9.5 years; range, 14-50 years; 78 females, 58.6%) completed questionnaires regarding demographics, pain, symptoms, and function and underwent a 3-T MRI scan of their more symptomatic eligible knee. Structural MRI abnormalities were scored with the MOAKS (Magnetic Resonance Imaging Osteoarthritis Knee Score), and MRI alignment and shape were measured with standardized methods. Associations among MOAKS features, PFP symptoms, and alignment and shape measures were evaluated with regression analyses (a = .05). Results: Minor cartilage defects were present in 22 (16.5%) participants, patellar osteophytes in 83 (62.4%), anterior femur osteophytes in 29 (21.8%), Hoffa synovitis in 81 (60.9%), and prefemoral fat pad synovitis in 49 (36.8%). A larger Insall-Salvati ratio was significantly associated with the presence of patellar osteophytes (odds ratio [OR], 51.82; 95% CI, 4.20-640.01), Hoffa synovitis (OR, 60.37; 95% CI, 4.66-782.61), and prefemoral fat pad synovitis (OR, 43.31; 95% CI, 4.28-438.72) in the patellofemoral joint. A larger patellar tilt angle was significantly associated with the presence of minor cartilage defects (OR, 1.10; 95% CI, 1.00- 1.20), the presence of patellar osteophytes (OR 1.12; 95%CI 1.02-1.22), and prefemoral fat pad synovitis (OR, 1.11; 95% CI, 1.03- 1.20) in the patellofemoral joint. Finally, a larger bisect offset was significantly associated with the presence of minor cartilage defects (OR, 1.05; 95% CI, 1.00-1.11) and patellar osteophytes (OR, 1.07; 95% CI, 1.01-1.14) in the patellofemoral joint. The majority of patellofemoral alignment measures were not associated with symptoms or function. Conclusion: For people with PFP, the presence of morphological abnormalities defined on MRI appears to be related to particular patellofemoral alignment measures, including higher Insall-Salvati ratio (indicating patella alta), larger patellar tilt angle (indicating greater lateral tilt), and larger bisect offset (indicating greater lateral displacement). Hardly any associations were found with symptoms or function. So there might be a distinct subgroup of PFP that is more prone to developing patellofemoral osteoarthritis later in life, as particular alignment measures seem to be associated with the presence of patellar osteophytes. Prospective studies are required to investigate the longitudinal relationship between alignment or bony shape and morphological abnormalities defined on MRI in this patient population. [ABSTRACT FROM AUTHOR]

Background: Cam impingement is a well-recognized cause of hip pain and might cause osteoarthritis of the hip. Clinically, cam impingement is mostly observed in young, active male patients, but only a few studies have focused on the manifestation of cam-type deformities during skeletal development.Purpose: To determine the age of onset and prevalence of cam-type deformities in young male soccer players versus controls.Study Design: Cross-sectional study; Level of evidence, 3.Methods: In this study, 89 elite preprofessional soccer players and 92 controls aged 12 to 19 years were included. In the soccer players, range of motion and impingement tests were performed. Both an anteroposterior (AP) pelvic radiograph and a frog-leg lateral radiograph of the hip were obtained according to a standardized protocol. Controls with both an AP pelvic and a frog-leg lateral radiograph and no hip disorders were obtained from radiology databases. The α angle was automatically determined in all radiographs, using a threshold value of 60° to define a cam-type deformity. Further, all radiographs were scored using a 3-point scoring system. The anterosuperior head-neck junction was classified as (1) normal, (2) flattened, or (3) having a prominence. Differences in prevalence were tested using logistic regression. Differences in range of motion were calculated using generalized estimating equations.Results: An α angle >60° was already found at the age of 12 years in some soccer players and controls. A cam-type deformity defined by α angle tended to be more prevalent in soccer players (26%) than in controls (17%; P = .31). In 13% of soccer players, a prominence was visible on radiographs and was first seen at the age of 13 years. The anterosuperior flattening (56% vs 18%, P = .0001) and prominence (13% vs 0%, P < .03) were more prevalent in soccer players than in controls.Conclusion: Cam-type deformities were recognizable and present from the age of 13 years and were more prevalent in soccer players than in their nonathletic peers. Cam-type deformity develops during adolescence and is likely to be influenced by high-impact sports practice. [ABSTRACT FROM PUBLISHER]