In Vivo Contrast-Enhanced Cone Beam CT Provides Quantitative Information on Articular Cartilage and Subchondral Bone.

In post-traumatic osteoarthritis, both articular cartilage and subchondral bone undergo characteristic pathological changes. This study investigates potential of delayed cone beam computed tomography arthrography (dCBCTa) to simultaneously detect variations in cartilage and subchondral bone. The knees of patients (n = 17) with suspected joint injuries were imaged using a clinical CBCT scanner at 5 and 45 min after the intra-articular injection of anionic contrast agent (Hexabrix™) with hydroxyapatite phantoms around the knee. Normalized attenuation (i.e., contrast agent partition, an indicator of tissue composition) in cartilage, bone mineral density (BMD) in subchondral bone plate (SBP), subchondral bone and trabecular bone, and thicknesses of SBP and cartilage were determined. Lesions of cartilage were scored using International Cartilage Repair Society (ICRS) grading. Normalized attenuation in the delayed image (t = 45 min) increased along the increase of ICRS grade (p = 0.046). Moreover, BMD was significantly higher in SBPs under damaged cartilage (ICRS = 1-2 or ICRS ≥ 3; p = 0.047 and p = 0.038, respectively) than in SBP under non-injured tissue (ICRS = 0). For the first time, dCBCTa enabled the detection of articular cartilage injuries and subchondral bone alterations simultaneously in vivo. Significant relations between ICRS grading and both cartilage and bone parameters suggest that dCBCTa has potential for quantitative imaging of the knee joint.

Modeling of interstitial fluid movement in soft tissue under negative pressure--relevance to treatment of tissue swelling.

Exact physiological mechanisms behind the potential positive treatment effects of pathological tissue swelling (edema), such as increased interstitial fluid flow, are poorly understood. Finite-element model was created and the model response was matched with the deformation data from the negative pressure (suction) measurements in human (N = 11) forearm. Two experimental suction protocols were simulated to evaluate their impact on interstitial fluid flow in soft tissues. Simulated continuous suction was up to 27 times more efficient in fluid transportation compared to the cyclic suction. The continuous suction that transports the interstitial fluid effectively may help to decrease soft tissue edema.

Short-term exercise-induced improvements in bone properties are for the most part not maintained during aging in hamsters.

Physical exercise during growth affects composition, structure and mechanical properties of bone. In this study we investigated whether the beneficial effects of exercise during the early growth phase have long-lasting effects or not. Female Syrian golden hamsters (total n=152) were used in this study. Half of the hamsters had access to running wheels during their rapid growth phase (from 1 to 3months of age). The hamsters were sacrificed at the ages of 1, 3, 12, and 15months. The diaphysis of the mineralized humerus was analyzed with microCT and subjected to three-point-bending mechanical testing. The trabecular bone in the tibial metaphysis was also analyzed with microCT. The collagen matrix of the humerus bone was studied by tensile testing after decalcification. The weight of the hamsters as well as the length of the bone and the volumetric bone mineral density (BMDvol) of the humerus was higher in the running group at the early age (3months). Moreover, the mineralized bone showed improved mechanical properties in humerus and had greater trabecular thickness in the subchondral bone of tibia in the runners. However, by the age of 12 and 15months, these differences were equalized with the sedentary group. The tensile strength and Young's modulus of decalcified humerus were higher in the runners at early stage, indicating a stronger collagen network. In tibial metaphysis, trabecular thickness was significantly higher for the runners in the old age groups (12 and 15months). Our study demonstrates that physical exercise during growth improves either directly or indirectly through weight gain bone properties of the hamsters. However, the beneficial effects were for the most part not maintained during aging.

Experimental and computational analysis of soft tissue mechanical response under negative pressure in forearm.

BACKGROUND: Instrumentation, relying on the use of negative pressure (suction), has been introduced to reduce pathological tissue swelling. Then, relative contribution of skin, adipose tissue and muscle, to the overall mechanical response is not known. METHODS: Under suction, stretch of soft tissues in the forearm of human subjects (N = 11) was experimentally measured at rest and under venous occlusion. Three dimensional, fibril-reinforced hyperelastic finite element (FE) model was constructed, the model response was matched with the experimental measurement and the mechanical characteristics of each tissue were derived. Parametric analyses were conducted to evaluate the impact of different tissues on the total stretch. RESULTS: The model suggested that, at large strains, the stretch response was more sensitive to changes in the elastic modulus of skin than those in adipose tissue. During venous occlusion, reduction of the stretch of forearm tissues was related to stiffening of the skin and adipose tissue, as evidenced by increased modulus of 27 ± 21% and 35 ± 26%, respectively. CONCLUSION: The method based on suction may be used to diagnose and monitor changes in properties of soft tissues, especially those of skin, as well as tissue swelling typical to pathological conditions such as oedema.

Experimental and computational analysis of soft tissue stiffness in forearm using a manual indentation device.

A hand held stiffness meter can be used to measure indentation stiffness of human soft tissues, sensitively altered, e.g., by pathological tissue swelling. Under indentation load, the relative contribution of each soft tissue component (i.e., skin, adipose tissue and muscle) to the biomechanical response is not known. In the present study, we evaluated the biomechanical role of different soft tissues in relaxed, physically stressed and oedemic human forearm. Soft tissue stiffness of the forearms of nine healthy human subjects was measured under four different test protocols: (1) forearm at rest, (2) forearm under isometric flexor loading, (3) forearm under isometric extensor loading, and (4) forearm under venous occlusion. In (2) and (3) the loading forces were monitored using a dynamometer, and in (4) the soft tissue swelling was induced by venous occlusion using a pressure cuff. At the site of indentation, thickness of different tissue layers (skin, adipose tissue and muscle) was measured using B-mode ultrasound imaging. Layered, hyperelastic finite element (FE) model of the indentation measurement was created and the model response was matched with that of the stiffness meter to determine the elastic modulus for each tissue in the model. Optimized values of the elastic modulus for skin and adipose tissue at rest were 210 kPa and 1.9 kPa, respectively. Further, significance of the variations in stiffness of different tissues on the indentation response was tested. Experimentally, indentation stiffness of the forearm increased during isometric extensor and flexor loads as well as under venous occlusion by 53, 91 and 15%, respectively. The FE model could reproduce the experimental responses primarily by the increased modulus of skin; 112% (446 kPa), 210% (651 kPa) and 21% (254 kPa) under flexor and extensor loading as well as during venous occlusion, respectively. The indentation response was 9-16 times more sensitive to changes in the mechanical properties of skin than those of adipose tissue and muscle. In conclusion, the present stiffness meter may be used to quantify in vivo mechanical properties of soft tissues in the forearm, sensitively modulated by soft tissue swelling and muscle loading.

Effects of growth and exercise on composition, structural maturation and appearance of osteoarthritis in articular cartilage of hamsters.

Articular cartilage composition and structure are maintained and remodeled by chondrocytes under the influence of loading. Exercise-induced changes in the composition, structure, mechanical properties and tissue integrity of growing and aging hamster articular cartilage were investigated. Articular cartilage samples (n = 191) were harvested from the proximal tibiae of hamsters aged 1, 3, 6, 12 and 15 months. The hamsters were divided into runners and controls. The runners had free access to a running wheel between 1 and 3 months (runner groups 3-, 12- and 15-month-old hamsters) or 1 and 6 months (runner group 6-month-old hamsters) of age. Control animals were subjected to a sedentary lifestyle. Mechanical indentation tests and depth-wise compositional and structural analyses were performed for the cartilage samples. Furthermore, the integrity of articular cartilage was assessed using histological osteoarthritis grading. Exercise affected the collagen network organization after a 5-month exercise period, especially in the middle and deep zones. However, no effect on the mechanical properties was detected after exercise. Before the age of 12 months, the runners showed less osteoarthritis than the controls, whereas at 15 months of age the situation was reversed. It is concluded that, in hamsters, physical exercise at a young age enhances cartilage maturation and alters the depth-wise cartilage structure and composition. This may be considered beneficial. However, exercise at a young age demonstrated adverse effects on cartilage at a later age with a significant increase in the incidence of osteoarthritis.

Collagen and mineral deposition in rabbit cortical bone during maturation and growth: effects on tissue properties.

We characterized the composition and mechanical properties of cortical bone during maturation and growth and in adult life in the rabbit. We hypothesized that the collagen network develops earlier than the mineralized matrix. Growth was monitored, and the rabbits were euthanized at birth (newborn), and at 1, 3, 6, 9, and 18 months of age. The collagen network was assessed biochemically (collagen content, enzymatic and non-enzymatic cross-links) in specimens from the mid-diaphysis of the tibia and femur and biomechanically (tensile testing) from decalcified whole tibia specimens. The mineralized matrix was analyzed using pQCT and 3-point bend tests from intact femur specimens. The collagen content and the Young's modulus of the collagen matrix increased significantly until the rabbits were 3 months old, and thereafter remained stable. The amount of HP and LP collagen cross-links increased continuously from newborn to 18 months of age, whereas PEN cross-links increased after 6 months of age. Bone mineral density and the Young's modulus of the mineralized bone increased until the rabbits were at least 6 months old. We concluded that substantial changes take place during the normal process of development in both the biochemical and biomechanical properties of rabbit cortical bone. In cortical bone, the collagen network reaches its mature composition and mechanical strength prior to the mineralized matrix.

Long-term voluntary exercise of male mice induces more beneficial effects on cancellous and cortical bone than on the collagenous matrix.

The effects of lifelong physical exercise on the composition, structure and mechanical properties of bone are not well understood. Earlier, we found that voluntary physical exercise improved various properties of bone in maturing male mice up to 6 months of age. In this study, we extended the previous study to 18 months. Half of the mice (total N=144) had access to running wheels while half were kept sedentary. The collagen network was assessed biochemically and by tensile testing of decalcified bone. The mineralized femur was analyzed with pQCT and three-point-bending of the diaphysis and neck-strength-test. The proximal tibia was analyzed with microCT. The bone collagen revealed inferior tensional properties with aging and the mineralized femur demonstrated decreased stiffness with age. In the running mice, tensile properties and the BMD were reduced at 18 months of age compared to the sedentary mice. In contrast, the stiffness of both the diaphysis and femoral neck was higher, and trabecular architecture and structure were improved in the running mice. In summary, the results suggest that lifelong exercise training of male mice results in more beneficial effects on intact mineralized bone in both the diaphysis and epiphysis than on bone collagenous matrix.

Physical exercise improves properties of bone and its collagen network in growing and maturing mice.

This study characterized bone structure, composition, and mechanical properties in growing male mice. The development of the collagen network during maturation was monitored, and the effect of voluntary physical exercise was investigated. We hypothesized that increased bone loading from exercise would increase the amount and improve the properties of the collagen network during growth and maturation. Half of the mice (total n = 168) had access to running wheels, while half were kept sedentary. Weight and running activity were recorded, and groups of mice were killed at 1, 2, 4, and 6 months of age. The collagen network was assessed by biochemical evaluation of collagen content and cross-links and by tensile testing of decalcified bone. Mineralized femur was analyzed with pQCT and three-point-bending and femoral neck-strength tests. After 6 months, the exercising mice had 10% lower body weight than the sedentary group. There was no difference in the amount of collagen or collagen cross-links, while tensile testing had higher breaking force and stiffness of the collagen network in runners after 4 months but not after 6 months. The bone mineral density and cross-sectional area were higher in the running group after 6 months. Runners also showed higher breaking force and stiffness of the diaphysis and the femoral neck at 2 and 6 months. The significant modulation of mechanical properties of the collagen network without any change in collagen content indicates that physical exercise improves properties of the collagen network in maturing bone. The improvement after exercise of the properties of mineralized bone appears to be more pronounced and long-lasting compared to the early improved properties of the collagen network.