Habitual side-specific loading leads to structural, mechanical, and compositional changes in the patellar tendon of young and senior lifelong male athletes.

Effects of lifelong physical activity on tendon function have been investigated in cross-sectional studies, but these are at risk of "survivorship" bias. Here, we investigate whether lifelong side-specific loading is associated with greater cross-sectional area (CSA), mechanical properties, cell density (DNA content), and collagen cross-link composition of the male human patellar tendon (PT), in vivo. Nine seniors and six young male lifelong elite badminton players and fencers were included. CSA of the PT obtained by 3-tesla MRI and ultrasonography-based bilateral PT mechanics were assessed. Collagen fibril characteristics, enzymatic cross links, nonenzymatic glycation (autofluorescence), collagen, and DNA content were measured biochemically in PT biopsies. The elite athletes had a ≥15% side-to-side difference in maximal knee extensor strength, reflecting chronic unilateral sport-specific loading patterns. The PT CSA was greater on the lead extremity compared with the nonlead extremity (17%, P = 0.0001). Furthermore, greater tendon stiffness (18%, P = 0.0404) together with lower tendon stress (22%, P = 0.0005) and tendon strain (18%, P = 0.0433) were observed on the lead extremity. No effects were demonstrated from side-to-side for glycation, enzymatic cross link, collagen, and DNA content (50%, P = 0.1160). Moreover, tendon fibril density was 87 ± 28 fibrils/µm2 on the lead extremity and 68 ± 26 fibrils/µm2 on the nonlead extremity (28%, P = 0.0544). Tendon fibril diameter was 86 ± 14 nm on the lead extremity and 94 ± 14 nm on the nonlead extremity (-9%, P = 0.1076). These novel data suggest that lifelong side-specific loading in males yields greater patellar tendon size and stiffness possibly with concomitant greater fibril density but without changes of collagen cross-link composition.NEW & NOTEWORTHY The present data demonstrate that lifelong side-specific loading yields greater patellar tendon structure on the lead extremity without affecting glycation that is associated with aging. These novel data suggest that lifelong side-specific habitual loading induce structural alterations that may serve to improve the mechanical properties of the tendon.

Weight-bearing MRI of the Lumbar Spine: Technical Aspects.

Magnetic resonance imaging (MRI) has an established role in the assessment of degenerative musculoskeletal conditions. However, conventional supine MRI findings often correlate poorly with clinical findings. Some patients experience accentuated back pain in the weight-bearing position. Therefore, supine MRI may underestimate the severity of degenerative spine findings. To try and improve the clinical validity of spine imaging, axial loading devices have been used with conventional supine MR imaging to simulate loading of the upright spine. More recently, upright weight-bearing MRI systems (0.25-0.6 T) were introduced, allowing images to be obtained in the standing or seated weight-bearing position and even during upright flexion or extension, rotation, or bending. Some scanners even enable capturing of real-time spinal movement. This review addresses the technical aspects and potential challenges of weight-bearing MRI, both in clinical practice and research.

Exercise-induced pain changes associate with changes in muscle perfusion in knee osteoarthritis: exploratory outcome analyses of a randomised controlled trial.

BACKGROUND: Exercise therapy is recommended for knee osteoarthritis (OA), but the underlying mechanisms of pain relief are not fully understood. The purpose of this study was to explore the effects of exercise on muscle perfusion assessed by dynamic contrast enhanced MRI (DCE-MRI) and its association with changes in pain in patients with knee OA. METHODS: Exploratory outcome analyses of a randomised controlled study with per-protocol analyses ( ClinicalTrials.gov : NCT01545258) performed at an outpatient clinic at a public hospital in Denmark. We compared 12 weeks of supervised exercise therapy 3 times per week (ET) with a no attention control group (CG). Analyses of covariance (ANCOVA) were used to assess group mean differences in changes from baseline to week 12 in knee muscle perfusion quantified by DCE-MRI, patient-reported pain and function using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, knee extensor and flexor muscle strength tests, and the six-minute walking test (6MWT). Spearman's correlation coefficients were used to determine the correlation between changes in DCE-MRI variables, KOOS, muscle strength, and 6MWT. The potential effect mediation of the DCE-MRI perfusion variables was investigated in a post-hoc mediation analysis. RESULTS: Of 60 participants randomised with knee osteoarthritis, 33 (ET, n = 16, CG, n = 17) adhered to the protocol and had complete DCE-MRI data. At follow-up, there were significant group differences in muscle perfusion changes and clinically relevant group differences in KOOS pain changes (10.7, 95% CI 3.3 to 18.1, P = 0.006) in favor of ET. There were no significant between-group differences on muscle strength and function. The changes in pain and muscle perfusion were significantly correlated (highest Spearman's rho = 0.42, P = 0.014). The mediation analyses were generally not statistically significant. CONCLUSION: The pain-reducing effects of a 12-week exercise program are associated with changes in knee muscle perfusion quantified by DCE-MRI in individuals with knee OA, but whether the effects are mediated by muscle perfusion changes remains unclear. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01545258 , first posted March 6, 2012.

Brain resting-state connectivity in the development of secondary hyperalgesia in healthy men.

Central sensitization is a condition in which there is an abnormal responsiveness to nociceptive stimuli. As such, the process may contribute to the development and maintenance of pain. Factors influencing the propensity for development of central sensitization have been a subject of intense debate and remain elusive. Injury-induced secondary hyperalgesia can be elicited by experimental pain models in humans, and is believed to be a result of central sensitization. Secondary hyperalgesia may thus reflect the individual level of central sensitization. The objective of this study was to investigate possible associations between increasing size of secondary hyperalgesia area and brain connectivity in known resting-state networks. We recruited 121 healthy participants (male, age 22, SD 3.35) who underwent resting-state functional magnetic resonance imaging. Prior to the scan session, areas of secondary hyperalgesia following brief thermal sensitization (3 min. 45 °C heat stimulation) were evaluated in all participants. 115 participants were included in the final analysis. We found a positive correlation (increasing connectivity) with increasing area of secondary hyperalgesia in the sensorimotor- and default mode networks. We also observed a negative correlation (decreasing connectivity) with increasing secondary hyperalgesia area in the sensorimotor-, fronto-parietal-, and default mode networks. Our findings indicate that increasing area of secondary hyperalgesia is associated with increasing and decreasing connectivity in multiple networks, suggesting that differences in the propensity for central sensitization, assessed as secondary hyperalgesia areas, may be expressed as differences in the resting-state central neuronal activity.

Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial.

Visceral adipose tissue is harmful to metabolic health. Exercise training reduces visceral adipose tissue mass, but the underlying mechanisms are not known. Interleukin-6 (IL-6) stimulates lipolysis and is released from skeletal muscle during exercise. We hypothesized that exercise-induced reductions in visceral adipose tissue mass are mediated by IL-6. In this randomized placebo-controlled trial, we assigned abdominally obese adults to tocilizumab (IL-6 receptor antibody) or placebo during a 12-week intervention with either bicycle exercise or no exercise. While exercise reduced visceral adipose tissue mass, this effect of exercise was abolished in the presence of IL-6 blockade. Changes in body weight and total adipose tissue mass showed similar tendencies, whereas lean body mass did not differ between groups. Also, IL-6 blockade increased cholesterol levels, an effect not reversed by exercise. Thus, IL-6 is required for exercise to reduce visceral adipose tissue mass and emphasizes a potentially important metabolic consequence of IL-6 blockade.

MR Imaging of Joint Infection and Inflammation with Emphasis on Dynamic Contrast-Enhanced MR Imaging.

Contrast-enhanced MR imaging (CE-MR imaging) is recommended for diagnosis and monitoring of infectious and most inflammatory joint diseases. CE-MR imaging clearly differentiates soft and bony tissue from fluid collections and infectious debris. To improve imaging information, a dynamic CE-MR imaging sequence (DCE-MR imaging) sequence can be applied using fast T1-weighted sequential image acquisition during contrast injection. Use of DCE-MR imaging allows robust extraction of quantitative information regarding blood flow and capillary permeability, especially when dedicated analysis methods and software are used to analyze contrast kinetics. This article describes principles of DCE-MR imaging for the assessment of infectious and inflammatory joint diseases.

Significance of arterial spin labeling perfusion and susceptibility weighted imaging changes in patients with transient ischemic attack: a prospective cohort study.

BACKGROUND: In a prospective cohort of patients with transient ischemic attack (TIA), we investigated usefulness and feasibility of arterial spin labeling (ASL) perfusion and susceptibility weighted imaging (SWI) alone and in combination with standard diffusion weighted (DWI) imaging in subacute diagnostic work-up. We investigated rates of ASL and SWI changes and their potential correlation to lasting infarction 8 weeks after ictus. METHODS: Patients with TIA underwent 3T-MRI including DWI, ASL and SWI within 72 h of symptom onset. We defined lasting infarction as presence of 8-week MRI T2-fluid attenuated inversion recovery (FLAIR) hyperintensity or atrophy in the area of initial DWI-lesion. RESULTS: We included 116 patients. Diffusion and perfusion together identified more patients with ischemia than either alone (59% vs. 40%, p < 0.0001). The presence of both diffusion and perfusion lesions had the highest rate of 8-week gliosis scars, 65% (p < 0.0001). In white matter, DWI-restriction was the determinant factor for scar development. However, in cortical gray matter half of lesions with perfusion deficit left a scar, while lesions without perfusion change rarely resulted in scars (56% versus 21%, p = 0.03). SWI lesions were rare (6%) and a subset of perfusion lesions. SWI-lesions with DWI-lesions were all located in cortical gray matter and showed high scar rate. CONCLUSIONS: ASL perfusion increased ischemia detection in patients with TIA, and was most useful in conjunction with DWI. ASL was fast, robust and useful in a subacute clinical diagnostic setting. SWI had few positive findings and did not add information. TRIAL REGISTRATION: http://www.clinicaltrials.gov . Unique Identifier NCT01531946 , prospectively registered February 9, 2012.

Delayed gadolinium-enhanced MRI of menisci and cartilage (dGEMRIM/dGEMRIC) in obese patients with knee osteoarthritis: Cross-sectional study of 85 obese patients with intra-articular administered gadolinium contrast.

BACKGROUND: Early cartilage changes in knee osteoarthritis (OA) can be assessed by both intravenous (i.v.) and intra-articular (i.a.) delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). PURPOSE: To examine the relationship between i.a. dGEMRIC and delayed gadolinium-enhanced MRI of menisci (dGEMRIM), and to investigate if the approach can be used to assess the morphological degeneration of menisci in obese patients with knee OA. STUDY TYPE: Cross-sectional. POPULATION: Eighty-five obese patients with knee OA. FIELD STRENGTH/SEQUENCES: 1.5T. Inversion recovery sequence with four inversion times. ASSESSMENT: T1 relaxation times were calculated for posterior weight-bearing femoral cartilage and the posterior horns of the menisci. Meniscus degeneration sum score (0-2) was assessed as increased signal/no signal (1/0) and tear/no tear (1/0). STATISTICAL TESTS: T1 relaxation times were compared using Student's t-test. Comparison of cartilage and meniscus T1 relaxation times was done by regression analysis. Analysis of variance (ANOVA) was used for comparison of meniscal T1 relaxation times among the three summed morphological scores (0-2). Statistical analyses were performed with a level of significance at 0.05. RESULTS: For lateral menisci, morphology sum scores of 0, 1, and 2 were found in 13, 58, and 14 patients and for medial menisci in 2, 30, and 30 patients, respectively. Mean T1 relaxation times were 441 msec, 480 msec, and 497 msec for cartilage, lateral menisci, and medial menisci, respectively. T1 relaxation times for the menisci were similar (P = 0.53), and a weak correlation was found between dGEMRIC and dGEMRIM in the lateral compartments (R = 0.26). Comparing dGEMRIM between different morphology sum scores showed no differences (P > 0.4). DATA CONCLUSION: I.a. dGEMRIM showed no correlation between the degree of meniscal degeneration and meniscus T1 relaxation times. I.a. dGEMRIM do not seem to deliver useful information about meniscus degeneration to be suitable for clinical applications, but i.a. dGEMRIC may still be considered an alternative contrast-saving method for cartilage. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;48:1700-1706.

Small cortical grey matter lesions show no persistent infarction in transient ischaemic attack? A prospective cohort study.

OBJECTIVES: To find determining factors for persistent infarction signs in patients with transient ischaemic attack (TIA), herein initial diffusion lesion size, visibility on apparent diffusion coefficient (ADC) or fluid-attenuated inversion recovery (FLAIR) and location. DESIGN: Prospective cohort study of patients with clinical TIA receiving 3T-MRI within 72 hours of symptom onset and at 8-week follow-up. SETTING: Clinical workflow in a single tertiary stroke centre between February 2012 and June 2014. PARTICIPANTS: 199 candidate patients were recruited, 64 patients were excluded due to non-TIA discharge diagnosis or no 8-week MRI. 122 patients completed the study. PRIMARY OUTCOME MEASURES: The primary outcome was visible persistent infarction defined as 8-week FLAIR hyperintensity or atrophy corresponding to the initial diffusion-weighted imaging (DWI) lesion. RESULTS: 50 patients showed 84 initial DWI lesions. 29 (35%) DWI lesions did not result in infarction signs on 8-week FLAIR. 26 (90%, P<0.0001) reversing lesions were located in the cortical grey matter (cGM). cGM location (vs any other location) strongly predicted no 8-week infarction sign development (OR 0.02, 95% CI 0.001 to 0.17) or partial lesion area decrease (>30% of initial DWI-area, OR 14.10, 95% CI 3.61 to 54.72), adjusted for FLAIR-visibility, DWI-area, ADC-confirmation and time to scan (TTS) from symptom onset to baseline MRI. Acute FLAIR-visibility was a strong associated factor for persistent infarction signs (OR 33.06, 95% CI 2.94 to 1432.34). For cGM lesions area size was sole associated factor for persistent infarction signs with a 0.31 cm2 (area under the curve (AUC), 0.97) threshold. In eight (16%) DWI-positive patients, all lesions reversed fully. CONCLUSIONS: 16% of DWI-positive patients and one-third of acute DWI lesions caused no persistent infarction signs, especially small cGM lesions were not followed by development of persistent infarction signs. Late MRI after TIA is likely to be less useful in the clinical setting, and it is dubious if the absence of old vascular lesions can be taken as evidence of no prior ischaemic attacks. TRIAL REGISTRATION NUMBER: NCT01531946; Results.

Are Movement Artifacts in Magnetic Resonance Imaging a Real Problem?-A Narrative Review.

Movement artifacts compromise image quality and may interfere with interpretation, especially in magnetic resonance imaging (MRI) applications with low signal-to-noise ratio such as functional MRI or diffusion tensor imaging, and when imaging small lesions. High image resolution has high sensitivity to motion artifacts and often prolongs scan time that again aggravates movement artifacts. During the scan fast imaging techniques and sequences, optimal receiver coils, careful patient positioning, and instruction may minimize movement artifacts. Physiological noise sources are motion from respiration, flow and pulse coupled to cardiac cycles, from the swallowing reflex and small spontaneous head movements. Par example, in resting-state functional MRI spontaneous neuronal activity adds 1-2% of signal change, even under optimal conditions signal contributions from physiological noise remain a considerable fraction hereof. Movement tracking during imaging may allow for prospective correction or postprocessing steps separating signal and noise.

Comparison of 3- and 20-Gradient Direction Diffusion-Weighted Imaging in a Clinical Subacute Cohort of Patients with Transient Ischemic Attack: Application of Standard Vendor Protocols for Lesion Detection and Final Infarct Size Projection.

OBJECTIVE: Diffusion tensor imaging may aid brain ischemia assessment but is more time consuming than conventional diffusion-weighted imaging (DWI). We compared 3-gradient direction DWI (3DWI) and 20-gradient direction DWI (20DWI) standard vendor protocols in a hospital-based prospective cohort of patients with transient ischemic attack (TIA) for lesion detection, lesion brightness, predictability of persisting infarction, and final infarct size. METHODS: We performed 3T-magnetic resonance imaging including diffusion and T2-fluid attenuated inversion recovery (FLAIR) within 72 h and 8 weeks after ictus. Qualitative lesion brightness was assessed by visual inspection. We measured lesion area and brightness with manual regions of interest and compared with homologous normal tissue. RESULTS: 117 patients with clinical TIA showed 78 DWI lesions. 2 lesions showed only on 3DWI. No lesions were uniquely 20DWI positive. 3DWI was visually brightest for 34 lesions. 12 lesions were brightest on 20DWI. The median 3DWI lesion area was larger for lesions equally bright, or brightest on 20DWI [median (IQR) 39 (18-95) versus 18 (10-34) mm2, P = 0.007]. 3DWI showed highest measured relative lesion signal intensity [median (IQR) 0.77 (0.48-1.17) versus 0.58 (0.34-0.81), P = 0.0006]. 3DWI relative lesion signal intensity was not correlated to absolute signal intensity, but 20DWI performed less well for low-contrast lesions. 3DWI lesion size was an independent predictor of persistent infarction. 3-gradient direction apparent diffusion coefficient areas were closest to 8-week FLAIR infarct size. CONCLUSION: 3DWI detected more lesions and had higher relative lesion SI than 20DWI. 20DWI appeared blurred and did not add information. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique Identifier NCT01531946.

Can positional MRI predict dynamic changes in the medial plantar arch? An exploratory pilot study.

BACKGROUND: Positional MRI (pMRI) allows for three-dimensional visual assessment of navicular position. In this exploratory pilot study pMRI was validated against a stretch sensor device, which measures movement of the medial plantar arch. We hypothesized that a combined pMRI measure incorporating both vertical and medial displacement of the navicular bone induced by loading would be correlated with corresponding stretch sensor measurements. METHODS: 10 voluntary participants were included in the study. Both pMRI and subsequent stretch sensor measurements were performed in a) supine, b) standing and c) standing position with addition of 10 % body weight during static loading of the foot. Stretch sensor measurements were also performed during barefoot walking. RESULTS: The total change in navicular position measured by pMRI was 10.3 mm (CI: 7.0 to 13.5 mm). No further displacement occurred when adding 10 % bodyweight (mean difference: 0.7 mm (CI: -0.7 to 2.0 mm), P = 0.29). The total navicular displacement correlated with stretch sensor measurement under static loading conditions (Spearman's rho = 0.66, P = 0.04) but not with measurements during walking (Spearman's rho = 0.58, P = 0.08). CONCLUSIONS: Total navicular bone displacements determined by pMRI showed concurrent validity with stretch sensor measurements but only so under static loading conditions. Although assessment of total navicular displacement by combining concomitant vertical and medial navicular bone movements would appear advantageous compared to monoplanar measurement the combined measure did not seem to predict dynamic changes of the medial foot arch during walking, which are among several possible factors depending on different walking patterns.

Is the Volume of the Caudate Nuclei Associated With Area of Secondary Hyperalgesia? - Protocol for a 3-Tesla MRI Study of Healthy Volunteers.

BACKGROUND: Experience and development of pain may be influenced by a number of physiological, psychological, and psychosocial factors. In a previous study we found differences in neuronal activation to noxious stimulation, and microstructural neuroanatomical differences, when comparing healthy volunteers with differences in size of the area of secondary hyperalgesia following a standardized burn injury. OBJECTIVE: We aim to investigate the degree of association between the volume of pain-relevant structures in the brain and the size of the area of secondary hyperalgesia following brief thermal sensitization. METHODS: The study consists of one experimental day, in which whole-brain magnetic resonance imaging (MRI) scans will be conducted including T1-weighed three-dimensional anatomy scan, diffusion tensor imaging, and resting state functional MRI. Before the experimental day, all included participants will undergo experimental pain testing in a parallel study (Clinicaltrials.gov Identifier: NCT02527395). Results from this experimental pain testing, as well as the size of the area of secondary hyperalgesia from the included participants, will be extracted from this parallel study. RESULTS: The association between the volume of pain-relevant structures in the brain and the area of secondary hyperalgesia will be investigated by linear regression of the estimated best linear unbiased predictors on the individual volumes of the pain relevant brain structures. CONCLUSIONS: We plan to investigate the association between experimental pain testing parameters and the volume, connectivity, and resting state activity of pain-relevant structures in the brain. These results may improve our knowledge of the mechanisms responsible for the development of acute and chronic pain. CLINICALTRIAL: Danish Research Ethics Committee (identifier: H-15010473). Danish Data Protection Agency (identifier: RH-2015-149). Clinicaltrials.gov NCT02567318; http://clinicaltrials.gov/ct2/show/NCT02567318 (Archived by WebCite at http://www.webcitation.org/6i4OtP0Oi).

A computer-based method for precise detection and calculation of affected skin areas.

BACKGROUND: The aim of this study was to describe and validate a method to obtain reproducible and comparable results concerning extension of a specific skin area, unaffected by individual differences in body surface area. METHODS: A phantom simulating the human torso was equipped with three irregular areas representing the increasing extension of an affected skin area over time. A large sheet of flexible calques paper was placed at the phantom, and five clinicians copied the three irregular shapes two times, resulting in 60 copies. Subsequently, a digital photograph was taken of the calques papers with a clinical ruler placed at the margin. The images were postprocessed and measured in the program 'ImageJ' by two observers. An exact area measurement of the three irregular shapes was performed for comparison. RESULTS: We found an interobserver variation of 0·36% when comparing the measurements of all three areas. Comparing observer measurements with the exact areas size, we found an underestimate of 2·52%. We observed a tendency that the discrepancy in measurement increases when the measured area decreases. CONCLUSION: We find this method accurate, reproducible and easy to use. The presented method can be of help when documenting psoriasis and other dermatologic conditions as well as when exploring the effects of new types and variations of ultrasound-guided peripheral nerve blocks - especially in study volunteers.