Age-related quantitative MRI changes in healthy cartilage: Preliminary results

IntroductionElevated serum high sensitivity C-reactive protein (hsCRP) has been reported in established osteoarthritis (OA). The aim of this study was to determine whether serum levels of hsCRP are associated with the variation in tibial and patella cartilage volumes in women without evidence of OA.MethodsParticipants were recruited from a database established from the Australian electoral roll, and were aged 40 to 67 years, were not hysterectomized and had no significant knee pain or knee injury in the last 5 years. Tibial and patella cartilage volumes were measured from magnetic resonance imaging (MRI) of each woman's dominant knee and hsCRP measured in serum. Linear regression models were used to explore the major determinants of variation in both tibial and patella cartilage volume and to assess whether serum hsCRP made an independent contribution to variation in the volumes of cartilage in the two knee compartments.ResultsThe mean age of the 176 participants was 52.3 ± 6.6 years. Compared with a standard model for tibial cartilage volume that included bone area, age, smoking and alcohol status, the addition of an hsCRP term made an independent negative contribution to variation in tibial cartilage volume, irrespective of whether body mass index (BMI) was included in the model or not. By contrast, using a similar approach, hsCRP did not contribute independently to variation in patella cartilage volume.ConclusionIn asymptomatic women aged 40 to 67 years, serum hsCRP is independently negatively associated with the volume of tibial but not patella cartilage suggesting that subclinical inflammation may predispose to knee cartilage loss in the tibial compartment. This should be further assessed by a longitudinal study.

To examine whether the femoral trochlear groove angle (TGA) is a determinant of the patellar cartilage volume and patellar cartilage damage. Patellar cartilage was evaluated by MR imaging in 66 patients (22 males and 44 females) with knee pain. Fat-suppressed 3D spoiled gradient-echo images were used to calculate the cartilage volume and to grade the cartilage damage. The proximal and distal TGAs were measured from axial PD-weighted FSE MR images with fat suppression. For every increase in the TGA at the distal femur, the patellar cartilage volume was significantly increased by 6.07 × 10(-3)cm(3) (95% CI: 1.27 × 10(-3), 10.9 × 10(-3)) after adjustment for age, gender, and patellar bone volume (P < 0.05). The MR grade of medial patellar cartilage damage progressed as the distal TGA became narrower, although there was no significant correlation between the distal TGA and the MR grading of patellar cartilage damage. A more flattened distal TGA was associated with increased patellar cartilage volume. However, there was no association between TGA and patellar cartilage defects.

SAT0310 Use of Low Dose Aspirin is Associated with Reduced Medial Tibial Cartilage Loss in Symptomatic Osteoarthritis: Data from a Cohort Study

Tau becomes abnormally hyper-phosphorylated and aggregated in tauopathies like Alzheimers disease (AD). As age is the greatest risk factor for developing AD, it is important to understand how tau protein itself, and the pathways implicated in its turnover, change during aging. We investigated age-related changes in total and phosphorylated tau in brain samples from two cohorts of cognitively normal individuals spanning 19-74 years, without overt neurodegeneration. One cohort utilised resected tissue and the other used post-mortem tissue. Total soluble tau levels declined with age in both cohorts. Phosphorylated tau was undetectable in the post-mortem tissue but was clearly evident in the resected tissue and did not undergo significant age-related change. To ascertain if the decline in soluble tau was correlated with age-related changes in autophagy, three markers of autophagy were tested but only two appeared to increase with age and the third was unchanged. This implies that in individuals who do not develop neurodegeneration, there is an age-related reduction in soluble tau which could potentially be due to age-related changes in autophagy. Thus, to explore how an age-related increase in autophagy might influence tau-mediated dysfunctions in vivo, autophagy was enhanced in a Drosophila model and all age-related tau phenotypes were significantly ameliorated. These data shed light on age-related physiological changes in proteins implicated in AD and highlights the need to study pathways that may be responsible for these changes. It also demonstrates the therapeutic potential of interventions that upregulate turnover of aggregate-prone proteins during aging.

Quantitative MRI can detect early biochemical changes in cartilage; however, the conventional techniques only measure one parameter (e.g., T1 , T2 , and T1ρ ) at a time while also being comparatively slow. We implemented a 3D magnetic resonance fingerprinting (3D-MRF) technique for simultaneous, volumetric mapping of T1 , T2 , and T1ρ in knee articular cartilage in under 9 min. It is evaluated on 11 healthy volunteers (mean age: 53 ± 9 years), five mild knee osteoarthritis (OA) patients (Kellgren-Lawrence (KL) score: 2, mean age: 60 ± 4 years), and the National Institute of Standards and Technology (NIST)/International Society for Magnetic Resonance in Medicine (ISMRM) system phantom. Proton density image, and T1 , T2, T1ρ relaxation times, and B1 + were estimated in the NIST/ISMRM system phantom as well as in the human knee medial and lateral femur, medial and lateral tibia, and patellar cartilage. The repeatability and reproducibility of the proposed technique were assessed in the phantom using analysis of the Bland-Altman plots. The intrasubject repeatability was assessed with the coefficient of variation (CV) and root mean square CV (rmsCV). The Mann-Whitney U test was used to assess the difference between healthy subjects and mild knee OA patients. The Bland-Altman plots in the NIST/ISMRM phantom demonstrated an average difference of 0.001% ± 015%, 1.2% ±7.1%, and 0.47% ±3% between two scans from the same 3-T scanner (repeatability), and 0.002% ± 015%, 0.62% ±10.5%, and 0.97% ± 14% between the scans acquired on two different 3-T scanners (reproducibility) for T1 , T2 , and T1ρ , respectively. The in vivo knee study showed excellent repeatability with rmsCV less than 1%, 2%, and 1% for T1 , T2 , and T1ρ , respectively. T1ρ relaxation time in the mild knee OA patients was significantly higher (p< 0.05) than in healthy subjects. The proposed 3D-MRF sequence is fast, reproducible, robust to B1 + inhomogeneity, and can simultaneously measure the T1 , T2 , T1ρ , and B1 + volumetric maps of the knee joint in a single scan within a clinically feasible scan time.

Objective: Knee cartilage volume measurement requires significant time and training. Simplifying the measurement may improve feasibility. We investigated whether the area of cartilage shown on the middle slice of the medial and lateral tibial cartilages on sagittal MRI correlates with radiological features of osteoarthritis (OA), cartilage volume, and longitudinal change in cartilage volume.Methods: One hundred and seventy‐three subjects (normal and osteoarthritic), who had serial magnetic resonance imaging (cartilage volume measured) and baseline weight‐bearing antero–posterior radiographs of the same knee were examined.Results: In the lateral compartment, with increasing grade of OA there was a significant reduction in cartilage area. In the medial compartment, this was true for medial joint‐space narrowing (after adjusting for gender). There was a moderate to strong association between cartilage area and volume, especially in those with early or no OA. However, when change over time was examined, the strength of these relationships was weak.Conclusion: Our data suggests that cartilage area may provide a simple surrogate measure of cartilage volume, in cross‐sectional studies, after adjustment for gender: especially in subjects with early disease. However, before it can be widely used, further investigation will be required.

Considering the increase in life expectancy, there is a time-related decline in biological functions. Age-related changes are also observed in the circadian clock which directly leads to appropriate rhythms in the endocrine and metabolic pathways required for organism homeostasis. Circadian rhythms are affected by the sleep/wake cycle, environmental changes, and nutrition. The aim of this review is to show the relationship between age-related changes in circadian rhythms of physiological and molecular processes and nutritional differences in the elderly. Nutrition is an environmental factor that is particularly effective on peripheral clocks. Age-related physiological changes have an impact on nutrient intake and circadian processes. Considering the known effects of amino acid and energy intakes on peripheral and circadian clocks, it is thought that the change in circadian clocks in aging may occur due to anorexia due to physiological changes.

The primary objective of this study was to develop a computer-aided method for the quantification of three-dimensional (3-D) cartilage changes over time in knees with osteoarthritis (OA). We introduced a local coordinate system (LCS) for the femoral and tibial cartilage boundaries that provides a standardized representation of cartilage geometry, thickness, and volume. The LCS can be registered in different data sets from the same patient so that results can be directly compared. Cartilage boundaries are segmented from 3-D magnetic resonance (MR) slices with a semi-automated method and transformed into offset-maps, defined by the LCS. Volumes and thickness are computed from these offset-maps. Further anatomical labeling allows focal volumes to be evaluated in predefined subregions. The accuracy of the automated behavior of the method was assessed, without any human intervention, using realistic, synthetic 3-D MR images of a human knee. The error in thickness evaluation is lower than 0.12 mm for the tibia and femur. Cartilage volumes in anatomical subregions show a coefficient of variation ranging from 0.11% to 0.32%. This method improves noninvasive 3-D analysis of cartilage thickness and volume and is well suited for in vivo follow-up clinical studies of OA knees.

OP0130 Radiographic and Magnetic Resonance Imaging Markers Predict Cartilage Volume Loss and Knee Symptoms over 10.7 Years in Older Adults

Poor correlation of clinical signs with patellar cartilaginous changes

Evaluation of Acoustical Parameter Sensitivity to Age-Related and Osteoarthritic Changes in Articular Cartilage Using 50-MHz Ultrasound

1. Presbycusis, age-related hearing loss, is an ever increasing problem in our aging society. It involves changes in both the peripheral and central portions of the auditory system. The inferior colliculus (IC) has been shown to display age-related changes including decreased gamma-aminobutryic acid (GABA) levels, decreased glutamate decarboxylase levels, and decreased binding by GABAB receptors, as well as rearrangement of axon terminals in aging Fischer 344 (F344) rats. Age-related physiological changes have also been noted in the ICs of C57 and CBA mice. 2. Given the age-related alterations in the inhibitory neurotransmitter system, we hypothesized that aged F344 rats would show alterations in the physiological response properties of their IC neurons due to an imbalance in the relative levels of inhibition and excitation affecting the neuronal firing. 3. In vivo extracellular single-unit recordings were made from 297 IC neurons in ketamine/xylazine-anesthetized aged (24 mo) F344 rats. Locations of recorded units were determined from the electrode track marks and horseradish peroxidase marks. Results were compared with those obtained from young adult (3 mo) animals. 4. Average threshold increased from 25.4 dB SPL in young rats to 56.1 dB SPL in aged rats. 5. Although there was a reduction in the percentage of units recorded at either extreme of the frequency range in aged animals, the characteristic frequency (CF) range and mean did not differ between the two groups. 6. For the IC as a whole, no differences were noted in spontaneous activity, first spike latency, dynamic range, percentage of units with nonmonotonic contralateral CF tone rate/intensity functions (RIFs), or percentage of units sensitive to change in CF tone presentation rate. 7. In aged rats, a higher percentage of units was poorly responsive to auditory stimulation. 8. In the aged rat, there was a 12% reduction in the maximum discharge rate, a 12% increase in the percentage of units classified as onset in their temporal response pattern, and an 18% increase in the breadth of the isointensity functions at 30 dB above threshold. 9. Age-related changes in the central nucleus of the IC (CIC) frequently differed from those observed in the external cortex of the IC (ECIC). The percentage of units classified as having nonmonotonic contralateral tone RIFs decreased with age in the CIC but increased with age in the ECIC, and the percentage of units classified as onset in their temporal response pattern increased with age in the CIC but did not change with age in the ECIC. 10. The results of this study support the hypothesis that there is an age-related shift to higher intensities in the working range of most CIC units along with a small, selective deficit in inhibitory processing. When considered in conjunction with the mouse aging studies conducted by other researchers and with the results of a similar study of single units in the visual system (lateral geniculate nucleus) of young and aged rhesus monkeys, these results suggest that compensatory mechanisms are highly active in sensory systems as animals age. Despite deficits that lead to reduced input to the IC and neurochemical changes affecting neurotransmitter levels, IC neurons in aged rats are able to respond to most simple auditory stimuli in a fashion quite similar to that observed in young rats.

Occupational activity is associated with knee cartilage morphology in females

The global society is aging at an increasing rate, with a continually larger proportion of the population consisting of those over the age of 65. Age-related vascular changes have been demonstrated in ocular tissue, and the incidence and prevalence of diseases such as macular degeneration, glaucoma and vascular occlusive diseases increase significantly with age. This article reviews the current body of literature examining age-associated ocular vascular changes, and summarizes the aggregate findings. We discuss the potential role of the aging vasculature in the etiology of age-associated ocular disease, focusing on glaucoma. Our working hypothesis is that although advancing age is a physiological phenomenon, there are stepwise hemodynamic and vascular changes that occur, predisposing the eye and other tissue beds to pathological conditions. Advancing age does not independently give rise to disease, but does generate increasingly vulnerable vascular beds that are susceptible to further insults. These results compel a need for further investigation of age-related changes in ocular physiology and pathophysiology.

Accurate evaluation of morphological changes in articular cartilage are necessary for early detection of osteoarthritis (OA). 3T magnetic resonance imaging (MRI) has highly sensitive contrast resolution and is widely used clinically to detect OA. However, synchrotron radiation phase-contrast imaging computed tomography (SR-PCI) can also provide contrast to tissue interfaces that do not have sufficient absorption differences, with the added benefit of very high spatial resolution. Here, MRI was compared with SR-PCI for quantitative evaluation of human articular cartilage. Medial tibial condyles were harvested from non-OA donors and from OA patients receiving knee replacement surgery. Both imaging methods revealed that average cartilage thickness and cartilage volume were significantly reduced in the OA group, compared to the non-OA group. When comparing modalities, the superior resolution of SR-PCI enabled more precise mapping of the cartilage surface relative to MRI. As a result, MRI showed significantly higher average cartilage thickness and cartilage volume, compared to SR-PCI. These data highlight the potential for high-resolution imaging of articular cartilage using SR-PCI as a solution for early OA diagnosis. Recognizing current limitations of using a synchrotron for clinical imaging, we discuss its nascent utility for preclinical models, particularly longitudinal studies of live animal models of OA.