Confidence maps for reliable estimation of proton density fat fraction and R 2 * in the liver.

PURPOSE: The objective was to develop a fully automated algorithm that generates confidence maps to identify regions valid for analysis of quantitative proton density fat fraction (PDFF) and R 2 * $$ {R}_2^{\ast } $$ maps of the liver, generated with chemical shift-encoded MRI (CSE-MRI). Confidence maps are urgently needed for automated quality assurance, particularly with the emergence of automated segmentation and analysis algorithms. METHODS: Confidence maps for both PDFF and R 2 * $$ {R}_2^{\ast } $$ maps are generated based on goodness of fit, measured by normalized RMS error between measured complex signals and the CSE-MRI signal model. Based on Cramér-Rao lower bound and Monte-Carlo simulations, normalized RMS error threshold criteria were developed to identify unreliable regions in quantitative maps. Simulation, phantom, and in vivo clinical studies were included. To analyze the clinical data, a board-certified radiologist delineated regions of interest (ROIs) in each of the nine liver segments for PDFF and R 2 * $$ {R}_2^{\ast } $$ analysis in consecutive clinical CSE-MRI data sets. The percent area of ROIs in areas deemed unreliable by confidence maps was calculated to assess the impact of confidence maps on real-world clinical PDFF and R 2 * $$ {R}_2^{\ast } $$ measurements. RESULTS: Simulations and phantom studies demonstrated that the proposed algorithm successfully excluded regions with unreliable PDFF and R 2 * $$ {R}_2^{\ast } $$ measurements. ROI analysis by the radiologist revealed that 2.6% and 15% of the ROIs were placed in unreliable areas of PDFF and R 2 * $$ {R}_2^{\ast } $$ maps, as identified by confidence maps. CONCLUSION: A proposed confidence map algorithm that identifies reliable areas of PDFF and R 2 * $$ {R}_2^{\ast } $$ measurements from CSE-MRI acquisitions was successfully developed. It demonstrated technical and clinical feasibility.

A community-endorsed open-source lexicon for contrast agent-based perfusion MRI: A consensus guidelines report from the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI).

This manuscript describes the ISMRM OSIPI (Open Science Initiative for Perfusion Imaging) lexicon for dynamic contrast-enhanced and dynamic susceptibility-contrast MRI. The lexicon was developed by Taskforce 4.2 of OSIPI to provide standardized definitions of commonly used quantities, models, and analysis processes with the aim of reducing reporting variability. The taskforce was established in February 2020 and consists of medical physicists, engineers, clinicians, data and computer scientists, and DICOM (Digital Imaging and Communications in Medicine) standard experts. Members of the taskforce collaborated via a slack channel and quarterly virtual meetings. Members participated by defining lexicon items and reporting formats that were reviewed by at least two other members of the taskforce. Version 1.0.0 of the lexicon was subject to open review from the wider perfusion imaging community between January and March 2022, and endorsed by the Perfusion Study Group of the ISMRM in the summer of 2022. The initial scope of the lexicon was set by the taskforce and defined such that it contained a basic set of quantities, processes, and models to enable users to report an end-to-end analysis pipeline including kinetic model fitting. We also provide guidance on how to easily incorporate lexicon items and definitions into free-text descriptions (e.g., in manuscripts and other documentation) and introduce an XML-based pipeline encoding format to encode analyses using lexicon definitions in standardized and extensible machine-readable code. The lexicon is designed to be open-source and extendable, enabling ongoing expansion of its content. We hope that widespread adoption of lexicon terminology and reporting formats described herein will increase reproducibility within the field.

The ISMRM Open Science Initiative for Perfusion Imaging (OSIPI): Results from the OSIPI-Dynamic Contrast-Enhanced challenge.

PURPOSE: K trans $$ {K}^{\mathrm{trans}} $$ has often been proposed as a quantitative imaging biomarker for diagnosis, prognosis, and treatment response assessment for various tumors. None of the many software tools for K trans $$ {K}^{\mathrm{trans}} $$ quantification are standardized. The ISMRM Open Science Initiative for Perfusion Imaging-Dynamic Contrast-Enhanced (OSIPI-DCE) challenge was designed to benchmark methods to better help the efforts to standardize K trans $$ {K}^{\mathrm{trans}} $$ measurement. METHODS: A framework was created to evaluate K trans $$ {K}^{\mathrm{trans}} $$ values produced by DCE-MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for K trans $$ {K}^{\mathrm{trans}} $$ quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants' K trans $$ {K}^{\mathrm{trans}} $$ values, the applied software, and a standard operating procedure. These were evaluated using the proposed OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score defined with accuracy, repeatability, and reproducibility components. RESULTS: Across the 10 received submissions, the OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score ranged from 28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively (0-1 = lowest-highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in K trans $$ {K}^{\mathrm{trans}} $$ analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility. CONCLUSIONS: This study reports results from the OSIPI-DCE challenge and highlights the high inter-software variability within K trans $$ {K}^{\mathrm{trans}} $$ estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real-world clinical setting, many of these tools may perform differently with different benchmarking methodology.

Post-traumatic and OA-related lesions in the knee at baseline and 2 years after traumatic meniscal injury: Secondary analysis of a randomized controlled trial.

OBJECTIVE: To assess the presence of early degenerative changes on Magnetic Resonance Imaging (MRI) 24 months after a traumatic meniscal tear and to compare these changes in patients treated with arthroscopic partial meniscectomy or physical therapy plus optional delayed arthroscopic partial meniscectomy. DESIGN: We included patients aged 18-45 years with a recent onset, traumatic, MRI verified, isolated meniscal tear without radiographic osteoarthritis. Patients were randomized to arthroscopic partial meniscectomy or standardized physical therapy with optional delayed arthroscopic partial meniscectomy. MRIs at baseline and 24 months were scored using the MRI Osteoarthritis Knee Score (MOAKS). We compared baseline MRIs to healthy controls aged 18-40 years. The outcome was the progression of bone marrow lesions (BMLs), cartilage defects and osteophytes after 24 months in patients. RESULTS: We included 99 patients and 50 controls. At baseline, grade 2 and 3 BMLs were present in 26% of the patients (n = 26), compared to 2% of the controls (n = 1) (between group difference 24% (95% CI 15% to 34%)). In patients, 35% (n = 35) had one or more cartilage defects grade 1 or higher, compared to 2% of controls (n = 1) (between group difference 33% (95% CI 23% to 44%)). At 24 months MRI was available for 40 patients randomized to arthroscopic partial meniscectomy and 41 patients randomized to physical therapy. At 24 months 30% (n = 12) of the patients randomized to arthroscopic partial meniscectomy showed BML worsening, compared to 22% (n = 9) of the patients randomized to physical therapy (between group difference 8% (95% CI -11% to 27%)). Worsening of cartilage defects was present in 40% (n = 16) of the arthroscopic partial meniscectomy group, compared to 22% (n = 9) of the physical therapy group (between group difference 18% (95% CI -2% to 38%)). Of the patients who had no cartilage defect at baseline, 33% of the arthroscopic partial meniscectomy group had a new cartilage defect at follow-up compared to 14% of the physical therapy group. Osteophyte worsening was present in 18% (n = 7) of the arthroscopic partial meniscectomy group and 15% (n = 6) of the physical therapy group (between group difference 3% (95% CI -13% to 19%)). CONCLUSIONS: Our results might suggest more worsening of BMLs and cartilage defects with arthroscopic partial meniscectomy compared to physical therapy with optional delayed arthroscopic partial meniscectomy at 24-month follow-up in young patients with isolated traumatic meniscal tears without radiographic OA.

Up-and-coming Radiotracers for Imaging Pain Generators.

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.

Advanced Magnetic Resonance Imaging and Molecular Imaging of the Painful Knee.

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.

3D MRI in Osteoarthritis.

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.

Quantitative DCE-MRI demonstrates increased blood perfusion in Hoffa's fat pad signal abnormalities in knee osteoarthritis, but not in patellofemoral pain.

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.

Patellofemoral alignment and geometry and early signs of osteoarthritis are associated in patellofemoral pain population.

BACKGROUND: Patellofemoral pain (PFP) patients show increased prevalence of patellar malalignment. Structural and alignment abnormalities of the patellofemoral joint (PFJ) may play a role in development of PFP and patellofemoral osteoarthritis (PFOA). OBJECTIVES: Evaluating associations of patellofemoral alignment and femoral geometry with bony and cartilaginous abnormalities in PFP patients and healthy control subjects. METHODS: Data from a case-control study were used (64 PFP subjects, 70 control subjects, 57% female, age 23.2 (6.4)). Alignment and femoral geometry measures in the PFJ were determined using MRI. Structural abnormalities in the PFJ associated with OA (bone marrow lesions, osteophytes, minor cartilage defects and Hoffa-synovitis), quantified cartilage composition (T1ρ relaxation times) in the PFJ and perfusion within the patellar bone were examined using different MRI techniques. Associations were analyzed using regression analyses, adjusted for potential confounders. RESULTS: Lateral patellar tilt was negatively associated with presence of osteophytes on both patella (OR 0.91; 95% CI 0.84 to 0.98), anterior femur (OR 0.92; 95% CI 0.84 to 0.99) and minor cartilage defects on patella (OR 0.91; 95% CI 0.84 to 0.99). Patella alta was positively associated with the presence of bone marrow lesions in the patella and minor cartilage defects (OR 48.33; 95% CI 4.27 to 547.30 and OR 17.51; 95% CI 1.17 to 262.57, respectively). Patella alta and medial patellar translation were positively associated with T1ρ relaxation times within trochlear cartilage (ß 5.2; 95% CI 0.77 to 9.58, and 0.36; 95% CI 0.08 to 0.64, respectively). None of the alignment and geometry measures were associated with bone perfusion. CONCLUSION: Our study implies that associations between patellofemoral alignment and geometry and structural joint abnormalities linked to OA are already present in both PFP patients and healthy control subjects.

Dynamic contrast-enhanced MRI of the patellar bone: How to quantify perfusion.

PURPOSE: To identify the optimal combination of pharmacokinetic model and arterial input function (AIF) for quantitative analysis of blood perfusion in the patellar bone using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: This method design study used a random subset of five control subjects from an Institutional Review Board (IRB)-approved case-control study into patellofemoral pain, scanned on a 3T MR system with a contrast-enhanced time-resolved imaging of contrast kinetics (TRICKS) sequence. We systematically investigated the reproducibility of pharmacokinetic parameters for all combinations of Orton and Parker AIF models with Tofts, Extended Tofts (ETofts), and Brix pharmacokinetic models. Furthermore, we evaluated if the AIF should use literature parameters, be subject-specific, or group-specific. Model selection was based on the goodness-of-fit and the coefficient of variation of the pharmacokinetic parameters inside the patella. This extends previous studies that were not focused on the patella and did not evaluate as many combinations of arterial and pharmacokinetic models. RESULTS: The vascular component in the ETofts model could not reliably be recovered (coefficient of variation [CV] of vp >50%) and the Brix model parameters showed high variability of up to 20% for kel across good AIF models. Compared to group-specific AIF, the subject-specific AIF's mostly had higher residual. The best reproducibility and goodness-of-fit were obtained by combining Tofts' pharmacokinetic model with the group-specific Parker AIF. CONCLUSION: We identified several good combinations of pharmacokinetic models and AIF for quantitative analysis of perfusion in the patellar bone. The recommended combination is Tofts pharmacokinetic model combined with a group-specific Parker AIF model. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:848-858.

Blood perfusion of patellar bone measured by dynamic contrast-enhanced MRI in patients with patellofemoral pain: A case-control study.

BACKGROUND: Altered perfusion might play an important role in the pathophysiology of patellofemoral pain (PFP), a common knee complaint with unclear pathophysiology. PURPOSE: To investigate differences in dynamic contrast-enhanced (DCE)-MRI perfusion parameters between patients with PFP and healthy control subjects. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: Thirty-five adult patients with PFP and 44 healthy adult control subjects. FIELD STRENGTH/SEQUENCE: 3T DCE-MRI consisting of a sagittal, anterior-posterior, frequency-encoded, fat-suppressed 3D spoiled gradient-echo sequence with intravenous contrast administration. ASSESSMENT: Patellar bone volumes of interest (VOIs) were delineated by a blinded observer. Quantitative perfusion parameters (kep and ktrans ) were calculated from motion-compensated DCE-MRI data by fitting Tofts' model. Weighted mean and unweighted median values of kep and ktrans were computed within the patellar bone VOIs. STATISTICAL TESTS: Differences in patellar bone perfusion parameters were compared between groups by linear regression analyses, adjusted for confounders. RESULTS: Mean differences of weighted mean and unweighted median were 0.0039 (95% confidence interval [CI] -0.0013; 0.0091) and 0.0052 (95% CI -0.0078; 0.018) for ktrans , and 0.046 (95% CI -0.021; 0.11) and 0.069 (95% CI -0.017; 0.15) for kep , respectively. All perfusion parameters were not significantly different between groups (P-values: 0.32; 0.47 for ktrans , and 0.24; 0.15) for kep . However, a significant difference in variance between populations was observed for ktrans (P-value 0.007). DATA CONCLUSION: Higher patellar bone perfusion parameters were found in patients with PFP when compared to healthy control subjects, but these differences were not statistically significant. This result, and the observed significant difference in ktrans variance, warrant further research. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1344-1350.

Lower Pressure Pain Thresholds in Patellofemoral Pain Patients, Especially in Female Patients: A Cross-Sectional Case-Control Study.

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 PPT and 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 PPT was 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 = -12.2, 95% confidence interval [CI] = -17.3 to -7.1; contralateral knee: mean difference = -4.7, 95% CI = -10.1 to 0.52; contralateral arm: mean difference = -5.7, 95% CI = -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.

Exercise for treating patellofemoral pain syndrome.

BACKGROUND: Patellofemoral pain syndrome (PFPS) is a common knee problem, which particularly affects adolescents and young adults. PFPS, which is characterised by retropatellar (behind the kneecap) or peripatellar (around the kneecap) pain, is often referred to as anterior knee pain. The pain mostly occurs when load is put on the knee extensor mechanism when climbing stairs, squatting, running, cycling or sitting with flexed knees. Exercise therapy is often prescribed for this condition. OBJECTIVES: To assess the effects (benefits and harms) of exercise therapy aimed at reducing knee pain and improving knee function for people with patellofemoral pain syndrome. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (May 2014), the Cochrane Central Register of Controlled Trials (2014, Issue 4), MEDLINE (1946 to May 2014), EMBASE (1980 to 2014 Week 20), PEDro (to June 2014), CINAHL (1982 to May 2014) and AMED (1985 to May 2014), trial registers (to June 2014) and conference abstracts. SELECTION CRITERIA: Randomised and quasi-randomised trials evaluating the effect of exercise therapy on pain, function and recovery in adolescents and adults with patellofemoral pain syndrome. We included comparisons of exercise therapy versus control (e.g. no treatment) or versus another non-surgical therapy; or of different exercises or exercise programmes. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials based on pre-defined inclusion criteria, extracted data and assessed risk of bias. Where appropriate, we pooled data using either fixed-effect or random-effects methods. We selected the following seven outcomes for summarising the available evidence: pain during activity (short-term: ≤ 3 months); usual pain (short-term); pain during activity (long-term: > 3 months); usual pain (long-term); functional ability (short-term); functional ability (long-term); and recovery (long-term). MAIN RESULTS: In total, 31 heterogeneous trials including 1690 participants with patellofemoral pain are included in this review. There was considerable between-study variation in patient characteristics (e.g. activity level) and diagnostic criteria for study inclusion (e.g. minimum duration of symptoms) and exercise therapy. Eight trials, six of which were quasi-randomised, were at high risk of selection bias. We assessed most trials as being at high risk of performance bias and detection bias, which resulted from lack of blinding.The included studies, some of which contributed to more than one comparison, provided evidence for the following comparisons: exercise therapy versus control (10 trials); exercise therapy versus other conservative interventions (e.g. taping; eight trials evaluating different interventions); and different exercises or exercise programmes. The latter group comprised: supervised versus home exercises (two trials); closed kinetic chain (KC) versus open KC exercises (four trials); variants of closed KC exercises (two trials making different comparisons); other comparisons of other types of KC or miscellaneous exercises (five trials evaluating different interventions); hip and knee versus knee exercises (seven trials); hip versus knee exercises (two studies); and high- versus low-intensity exercises (one study). There were no trials testing exercise medium (land versus water) or duration of exercises. Where available, the evidence for each of seven main outcomes for all comparisons was of very low quality, generally due to serious flaws in design and small numbers of participants. This means that we are very unsure about the estimates. The evidence for the two largest comparisons is summarised here. Exercise versus control. Pooled data from five studies (375 participants) for pain during activity (short-term) favoured exercise therapy: mean difference (MD) -1.46, 95% confidence interval (CI) -2.39 to -0.54. The CI included the minimal clinically important difference (MCID) of 1.3 (scale 0 to 10), indicating the possibility of a clinically important reduction in pain. The same finding applied for usual pain (short-term; two studies, 41 participants), pain during activity (long-term; two studies, 180 participants) and usual pain (long-term; one study, 94 participants). Pooled data from seven studies (483 participants) for functional ability (short-term) also favoured exercise therapy; standardised mean difference (SMD) 1.10, 95% CI 0.58 to 1.63. Re-expressed in terms of the Anterior Knee Pain Score (AKPS; 0 to 100), this result (estimated MD 12.21 higher, 95% CI 6.44 to 18.09 higher) included the MCID of 10.0, indicating the possibility of a clinically important improvement in function. The same finding applied for functional ability (long-term; three studies, 274 participants). Pooled data (two studies, 166 participants) indicated that, based on the 'recovery' of 250 per 1000 in the control group, 88 more (95% CI 2 fewer to 210 more) participants per 1000 recovered in the long term (12 months) as a result of exercise therapy. Hip plus knee versus knee exercises. Pooled data from three studies (104 participants) for pain during activity (short-term) favoured hip and knee exercise: MD -2.20, 95% CI -3.80 to -0.60; the CI included a clinically important effect. The same applied for usual pain (short-term; two studies, 46 participants). One study (49 participants) found a clinically important reduction in pain during activity (long-term) for hip and knee exercise. Although tending to favour hip and knee exercises, the evidence for functional ability (short-term; four studies, 174 participants; and long-term; two studies, 78 participants) and recovery (one study, 29 participants) did not show that either approach was superior. AUTHORS' CONCLUSIONS: This review has found very low quality but consistent evidence that exercise therapy for PFPS may result in clinically important reduction in pain and improvement in functional ability, as well as enhancing long-term recovery. However, there is insufficient evidence to determine the best form of exercise therapy and it is unknown whether this result would apply to all people with PFPS. There is some very low quality evidence that hip plus knee exercises may be more effective in reducing pain than knee exercise alone.Further randomised trials are warranted but in order to optimise research effort and engender the large multicentre randomised trials that are required to inform practice, these should be preceded by research that aims to identify priority questions and attain agreement and, where practical, standardisation regarding diagnostic criteria and measurement of outcome.

Patellofemoral alignment, morphology and structural features are not related to sitting pain in individuals with patellofemoral pain.

BACKGROUND: Sitting-related pain is a common feature of patellofemoral pain (PFP). However, little is known regarding features associated with sitting-related PFP. The aim of this study was to determine whether sitting-related PFP is associated with patellofemoral alignment, morphology and structural magnetic resonance imaging (MRI) features of the patellofemoral joint (cartilage lesions, bone marrow lesions, fat pad synovitis). METHODS: 133 individuals with PFP were included from two unique but similar cohorts. Participants were classified into one of three groups based on their response to item 8 of the Anterior Knee Pain Scale: (i) problems with sitting; (ii) sitting pain after exercise; and (iii) no difficulty with sitting. All participants underwent 3T Magnetic Resonance Imaging (MRI) to enable: (i) scoring of structural features of the patellofemoral joint with MRI Osteoarthritis Knee Score (MOAKS); and (ii) patellofemoral alignment and morphology measurements using standardised methods. The association of sitting pain to bony alignment, morphology and MOAKS features were evaluated using multinomial logistic regression (adjusted for age, sex, BMI; reference group = no difficulty with sitting). RESULTS: 82 (61.7%) participants reported problems with sitting, and 24 (18%) participants reported sitting pain after exercise. There were no significant associations between the presence of sitting pain and any morphology, alignment or structural characteristics. CONCLUSIONS: Findings indicate that PFP related to sitting is not associated with patellofemoral alignment, morphology, or structural MRI features of the patellofemoral joint. Further research to determine mechanisms of sitting-related PFP, and inform targeted treatments, are required.

Quantitative volume and dynamic contrast-enhanced MRI derived perfusion of the infrapatellar fat pad in patellofemoral pain.

BACKGROUND: Patellofemoral pain (PFP) is a common knee condition and possible precursor of knee osteoarthritis (OA). Inflammation, leading to an increased perfusion, or increased volume of the infrapatellar fat pad (IPFP) may induce knee pain. The aim of the study was to compare quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters, as imaging biomarkers of inflammation, and volume of the IPFP between patients with PFP and controls and between patients with and without IPFP edema or joint effusion. METHODS: Patients with PFP and healthy controls were included and underwent non-fat suppressed 3D fast-spoiled gradient-echo (FSPGR) and DCE-MRI. Image registration was applied to correct for motion. The IPFP was delineated on FSPGR using Horos software. Volume was calculated and quantitative perfusion parameters were extracted by fitting extended Tofts' pharmacokinetic model. Differences in volume and DCE-MRI parameters between patients and controls were tested by linear regression analyses. IPFP edema and effusion were analyzed identically. RESULTS: Forty-three controls and 35 PFP patients were included. Mean IPFP volume was 26.04 (4.18) mL in control subjects and 27.52 (5.37) mL in patients. Median Ktrans was 0.017 (0.016) min-1 in control subjects and 0.016 (0.020) min-1 in patients. None of the differences in volume and perfusion parameters were statistically significant. Knees with effusion showed a higher perfusion of the IPFP compared to knees without effusion in patients only. CONCLUSIONS: The IPFP has been implicated as source of knee pain, but higher DCE-MR blood perfusion, an imaging biomarker of inflammation, and larger volume are not associated with PFP. Patient's knees with effusion showed a higher perfusion, pointing towards inflammation.

Quantitative subchondral bone perfusion imaging in knee osteoarthritis using dynamic contrast enhanced MRI.

OBJECTIVE: Subchondral bone changes, characterized by increased bone turnover and vascularity, are believed to stimulate progression and pain in knee osteoarthritis (OA). The objective of this study was to evaluate the bone perfusion in knee OA using quantitative dynamic contrast enhanced MRI (DCE-MRI). DESIGN: Unicompartmental knee OA patients were included and underwent 3 Tesla DCE-MRI and T2-weighted MRI. Quantitative DCE-MRI analysis of Ktrans and Kep, representing perfusion parameters, was performed to evaluate differences between the most and least affected knee compartment. First, DCE-MRI parameter differences between epimetaphyseal and subchondral bone in both femur and tibia were assessed. Second, DCE-MRI parameters in subchondral bone marrow lesions (BMLs) were compared to surrounding subchondral bone without BMLs. RESULTS: Twenty-three patients were analyzed. Median Ktrans and Kep in epimetaphyseal bone were significantly higher (p < 0.05) in the most affected (Ktrans: 0.014; Kep: 0.054 min-1) compared to least affected (Ktrans: 0.010; Kep: 0.016 min-1) compartment. For subchondral bone, DCE-MRI parameters were significantly higher (p < 0.05) in the most affected (Ktrans: 0.019; Kep: 0.091 min-1) compared to least affected (Ktrans: 0.014; Kep: 0.058 min-1) compartment as well. Subchondral BMLs detected on fat-saturated T2-weighted images were present in all patients. Median Ktrans (0.091 vs 0.000 min-1) and Kep (0.258 vs 0.000 min-1) were significantly higher within subchondral BMLs compared to surrounding subchondral bone without BMLs (p < 0.001). CONCLUSIONS: Increased perfusion parameters in epimetaphyseal bone, subchondral bone and BMLs are observed in unicompartmental knee OA. BMLs likely account for most of the effect of the higher bone perfusion in knee OA.

Association Between Self-reported Measures, Physical Examination, and Early Magnetic Resonance Imaging Signs of Osteoarthritis in Patients With Patellofemoral Pain.

BACKGROUND: Structural abnormalities associated with osteoarthritis (OA) are found in some patients with patellofemoral pain (PFP). OBJECTIVES: To investigate the association between early signs of OA on magnetic resonance imaging (MRI) and characteristics from self-reported measures and physical examination in patients with PFP. METHODS: This exploratory study included data from patients with PFP from a previously published cross-sectional case-control study (n = 64; 55% female; mean ± SD age, 23.4 ± 7.0 years). Structural OA features (osteophytes, bone marrow lesions, cartilage defects, Hoffa synovitis, patellar tendon abnormalities) and quantitative T2 measurements of cartilage composition were extracted from MRI. Associations between characteristics from self-reported measures (pain at rest, pain during stair walking, knee function, duration of complaints, hours of sports participation each week), physical examination (crepitus, quadriceps strength), and early MRI signs of OA were assessed. RESULTS: Symptom duration was associated with bone marrow lesions in the patella (odds ratio [OR] = 1.1; 95% confidence interval [CI]: 1.0, 1.2). Sports participation (hours per week) was inversely associated with patellar tendon abnormalities on MRI (OR = 0.8; 95% CI: 0.6, 1.0). Crepitus and bilateral nature of the complaints were associated with minor patellar cartilage defects (OR = 12.0; 95% CI: 2.3, 63.6 and OR = 7.6; 95% CI: 1.1, 53.8, respectively). There were no significant associations between clinical characteristics and cartilage T2 relaxation time. CONCLUSION: Presence of crepitus, bilateral complaints, a long PFP symptom duration, and reduced weekly sport participation were associated with early signs of OA in a young PFP population. LEVEL OF EVIDENCE: Etiology, level 2c. J Orthop Sports Phys Ther 2019;49(9):634-639. Epub 10 Jul 2019. doi:10.2519/jospt.2019.8889.

Are Patellofemoral Joint Alignment and Shape Associated With Structural Magnetic Resonance Imaging Abnormalities and Symptoms Among People With Patellofemoral Pain?

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 ± SD age, 30.2 ± 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 (α = .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.