Breast deformation during the course of radiotherapy: The need for an additional outer margin.

PURPOSE: The aim of this retrospective study was to investigate and quantify the extent of breast deformation during the course of breast cancer (BC) radiotherapy (RT). The magnitude of breast deformation determines the additional outer margin needed for treatment planning to deliver a full dose to the target volume. This is especially important when using inverse planning techniques. METHODS: A total of 93 BC patients treated with RT and with daily CBCT image guidance were selected for this study. Patients underwent either only breast-conserving surgery (BCS) (n = 5), BCS with sentinel node biopsy (n = 57) or BCS with radical axillary node dissection (n = 31). The treatment area included the whole breast and chest wall (54%) or also the axillary lymph nodes (46%). 3D-registration was conducted between 1731 CBCT images and the respective planning CT images to assess the difference in breast surface. RESULTS: The largest maximum breast surface expansion (MBSE) was 15 mm; the average was 2.4 ±â€¯2.1 mm. In 294 fractions (17%), the MBSE was ≥5 mm. An outer margin of 8 mm would have been required to cover the whole breast in 95% of the treated fractions. There was a statistically significant correlation between the MBSE and body mass index (r = 0.38, p = 0.001). CONCLUSIONS: Significant changes in the breast surface occur during the course of BC RT which should be considered in treatment planning. An additional margin outside the breast surface of at least 8 mm is required to take into account the anatomical changes occurring during BC RT.

Transport of Iodine Is Different in Cartilage and Meniscus.

Contrast enhanced computed tomography (CECT) has been proposed for diagnostics of cartilage and meniscus injuries and degeneration. As both tissues may be imaged simultaneously, CECT could provide a method for comprehensive evaluation of knee joint health. Since the composition and structure of cartilage and meniscus are different, we hypothesize that transport characteristics of anionic contrast agents also differ between the tissues. This would affect interpretation of CECT images and warrants investigation. To clarify this, we aimed to determine the transport kinematics of anionic iodine (q = -1, M = 126.9 g/mol), assumed to not be significantly affected by the steric hindrance, thus providing faster transport than large molecule contrast agents (e.g., ioxaglate). Cylindrical samples (d = 6 mm, h = 2 mm) were prepared from healthy bovine (n = 10) patella and meniscus, immersed in isotonic phosphate-buffered NaI solution (20 mgI/mL), and subsequently imaged with a micro-CT at 20 time points up to 23 h. Subsequently, normalized attenuation and contrast agent flux, as well as water, collagen, and proteoglycan (PG) contents in the tissues were determined. Normalized attenuation at equilibrium was higher (p = 0.005) in meniscus. Contrast agent flux was lower (p = 0.005) in the meniscus at 10 min, but higher (p < 0.05) between 30 and 120 min. In both tissues, contrast agent distribution at equilibrium suggested an inverse agreement with the depth-wise PG distribution. In conclusion, iodine transport into cartilage and meniscus was different, especially between the first 2 hours after the immersion. This is an important finding which should be considered during simultaneous CECT of cartilage and meniscus.

Contrast enhanced imaging of human meniscus using cone beam CT.

OBJECTIVE: Meniscal injuries can lead to mechanical overloading of articular cartilage and eventually to knee osteoarthritis. The objective was to evaluate the potential of contrast enhanced computed tomography (CECT) to image contrast agent (CA) diffusion in human menisci with a clinical cone beam CT scanner. DESIGN: Isolated human menisci (n = 26) were imaged using magnetic resonance imaging (MRI) and CECT in situ. Diffusion of anionic CA into the meniscus was imaged for up to 30 h. The results of CECT were compared with water, collagen and proteoglycan (PG) contents, biomechanical properties, age and histological and MR images of the samples. RESULTS: Diffusion of CA required over 25 h to reach equilibrium. The CA partition (the CA concentration in the tissue divided by that in the bath) at the 40 min time point correlated significantly with that at the 30 h time point in both lateral (r = 0.706, P = 0.007) and medial (r = 0.669, P = 0.012) menisci. Furthermore, CA partition in meniscus after 30 h of diffusion agreed qualitatively with the distribution of PGs. CONCLUSION: The cross-sectional distribution of CA was consistent with that reported in a previous µCT study on bovine meniscus. The time required to reach diffusion equilibrium was found impractical for clinical applications. However, based on the present results, shorter delay between injection and imaging (e.g., 40 min) could be feasible in clinical diagnostics of meniscal pathologies.

Characterization of site-specific biomechanical properties of human meniscus-Importance of collagen and fluid on mechanical nonlinearities.

Meniscus adapts to joint loads by depth- and site-specific variations in its composition and structure. However, site-specific mechanical characteristics of intact meniscus under compression are poorly known. In particular, mechanical nonlinearities caused by different meniscal constituents (collagen and fluid) are not known. In the current study, in situ indentation testing was conducted to determine site-specific elastic, viscoelastic and poroelastic properties of intact human menisci. Lateral and medial menisci (n=26) were harvested from the left knee joint of 13 human cadavers. Indentation tests, using stress-relaxation and dynamic (sinusoidal) loading protocols, were conducted for menisci at different sites (anterior, middle, posterior, n=78). Sample- and site-specific axisymmetric finite element models with fibril-reinforced poroelastic properties were fitted to the corresponding stress-relaxation curves to determine the mechanical parameters. Elastic moduli, especially the instantaneous and dynamic moduli, showed site-specific variation only in the medial meniscus (p<0.05 between the sites). The instantaneous and dynamic elastic moduli of the anterior horn were significantly (p<0.05) greater in the medial than lateral meniscus. The phase angle showed no statistically significant variation between the sites (p>0.05). The values for the strain-dependent fibril network modulus (nonlinear behaviour of collagen) were significantly different (p<0.05) between all sites in the medial menisci. Additionally, there was a significant difference (p<0.01) in the strain-dependent fibril network modulus between the lateral and medial anterior horns. The initial permeability was significantly different (p<0.05) in the medial meniscus only between the middle and posterior sites. For the strain-dependent permeability coefficient, only anterior and middle sites showed a significant difference (p<0.05) in the medial meniscus. This parameter demonstrated a significant difference (p<0.05) between lateral and medial menisci at the anterior horns. Our results reveal that under in situ indentation loading, medial meniscus shows more site-dependent variation in the mechanical properties as compared to lateral meniscus. In particular, anterior horn of medial meniscus was the stiffest and showed the most nonlinear mechanical behaviour. The nonlinearity was related to both collagen fibrils and fluid.

Comparison of nonlinear mechanical properties of bovine articular cartilage and meniscus.

Nonlinear, linear and failure properties of articular cartilage and meniscus in opposing contact surfaces are poorly known in tension. Relationships between the tensile properties of articular cartilage and meniscus in contact with each other within knee joints are also not known. In the present study, rectangular samples were prepared from the superficial lateral femoral condyle cartilage and lateral meniscus of bovine knee joints. Tensile tests were carried out with a loading rate of 5mm/min until the tissue rupture. Nonlinear properties of the toe region, linear properties in larger strains, and failure properties of both tissues were analysed. The strain-dependent tensile modulus of the toe region, Young's modulus of the linear region, ultimate tensile stress and toughness were on average 98.2, 8.3, 4.0 and 1.9 times greater (p<0.05) for meniscus than for articular cartilage. In contrast, the toe region strain, yield strain and failure strain were on average 9.4, 3.1 and 2.3 times greater (p<0.05) for cartilage than for meniscus. There was a significant negative correlation between the strain-dependent tensile moduli of meniscus and articular cartilage samples within the same joints (r=-0.690, p=0.014). In conclusion, the meniscus possesses higher nonlinear and linear elastic stiffness and energy absorption capability before rupture than contacting articular cartilage, while cartilage has longer nonlinear region and can withstand greater strains before failure. These findings point out different load carrying demands that both articular cartilage and meniscus have to fulfil during normal physiological loading activities of knee joints.