validation and quantification of an in vivo model of functional bone adaptation

1
Thread 4. Imaging bone quality and to integrate automatic region of interest (ROI) algorithm in trabecular bone assessment in the region of interest (ROI). Method: Total of 34 human cadaver calcanei, age from 60 to 97 years old, are tested by SCAD, micro-CT and DEXA, as well as mechanical strength. An imaging recognition algorithm is developed, integrated in a newly developed SCAD system. The method is designed for the selection of an irregular ROI in SCAD determined ultrasound attenuation images from bone. When the ROI is automatically determined through programmed ROI seeding and neighboring 500 pixels, broadband ultrasound attenuation (BUA), and ultrasound velocity (UV) in the real body region are evaluated. The SCAD properties are then correlated to the bone mineral density (BMD), ~tCT volume fraction, and bone moduli. Results: Strong correlations have found between BMD (DEXA) and SCAD parameters, yielding R2 =0.83 (BUA), and R2 =0.65 (UV). Correlation between bone volume fraction and BUA shows R2 =0.75, and shows R2 =0.54 (UV). SCAD parameters predict the trabecular bone strength, in which correlation between BUA and elastic modulus is R2=0.54, and correlation between ultimate strength and BUA is R2 =0.60. Discussion: These data have suggested that high resolution bone acous- tic images can be generated at particular ROI sites, e.g., calcaneus. Data have shown that ultrasound measurement significant correlate to ~tCT/DEXA determined bone architecture/density parameters, and particularly to bone's stiffness. These suggest that ultrasound imaging is capable to predict the quality of bone as a portable, noninvasive modality for applications in space and on Earth. Supported by the National Space Biomedical Research Institute (TD00207 & 00405) through NASA Cooperative Agreement NCC 9-58. 7222 We, 12:00-12:15 (P33) Prediction of the mechanical properties of normal and degenerated articular cartilage and trabecular bone using MRI E. Lammentausta 1, P. Kiviranta 1, J. T6yr~s2, M.T. Nieminen3, J.S. Jurvelin 1,2. 1University of Kuopio, Kuopio, Finland, 2Kuopio University Hospital, Kuopio, Finland, 30ulu University Hospital, Oulu, Finland Structural properties of articular cartilage and mineral density (BMD) of tra- becular bone have been assessed by quantitative MRI methods, such as T2 and T2* mapping, respectively [1,2,3]. As bone and cartilage are usually assessed separately, the sequence of earliest tissue changes leading to osteoarthritis remains unknown. Aim of the present study was to determine interrelationships between the mechanical properties of articular cartilage and underlying trabecular bone, and to determine the ability of MRI parameters to quantitatively distinguish healthy and degenerated cartilage. Cadaveric human patellae (n=14, age=55±18) were investigated. From intact patellae, MRI parameters (cartilage T2, bone T2*) were obtained with a 1.5-T clinical scanner. As a reference, BMD was measured with pQCT. Elastic modulus was measured separately for cylindrical samples of cartilage [4] and underlying bone [5]. Mankin scores [6] of the cartilage samples were microscopically evaluated from blind-coded sections and the samples were divided into three groups, representing healthy tissue (Mankin score <3.3), early degeneration (3.3-5.0) and advanced degeneration (>5.0). Healthy samples showed significantly (p<0.05) higher moduli (cartilage 0.76±0.46 MPa vs. 0.28±0.55 MPa, bone 627±319 MPa vs. 325±164 MPa) and BMD (426±102mg/cm 3 vs. 336±105mg/cm3), and lower cartilage T2 (40±5 ms vs 49±8 ms) than samples with advanced degeneration. The linear correlations were significant between T2 and cartilage modulus (r=0.42, p < 0.01) and between BMD and bone modulus (r = 0.44, p < 0.01). However, elastic moduli of cartilage and bone were not significantly interrelated. T2* of bone showed no differences between the groups or correlation with elastic modulus. This study indicates that parallel changes take place in cartilage and bone during cartilage degeneration. However, further research with optimized MRI techniques is required to resolve detailed interrelationships of these changes. References [1] Burstein D., Gray M.J. Bone Joint Surg Am. 2003; 85-A(Suppl 2): 70-7. [2] Grampp S, et al. Radiology 1996; 198: 213-218. [3] Wehrli FW, et al. Top Magn Reson Imaging 2002; 13: 335-35. [4] Jurvelin JS, et al. J Biomech 1997; 30: 235-241. [5] Turner CH, Burr DB. Bone 1993; 14: 595~08. [6] Mankin H J, et al. J Bone Joint Surg Am. 1971; 53: 523-537. T4.7 Quantitative Functional Imaging $451 7140 We, 12:15-12:30 (P33) Characteristic strain distribution on meniscus cross-sections under axial compression T. Augustin 1, O. Kessler 2, M. Bottlang 1. 1Biomechanics Laboratory, Legacy Research & Technology Center, Portland, Oregon; USA, 2Stryker Europe, Thalwil, Switzerland. Background: The meniscal ultra-structure is complex, being comprised of a highly oriented and non-homogeneous collagen fiber matrix which dominates its anisotropic behavior. This study aimed to deliver a functional character- ization of the complex meniscus structure using a novel laser-based strain mapping technique. Results of this study describe strain distributions on meniscus cross-sections under axial compression, as well as age-dependent changes thereof. Methods: Eight human medial menisci were harvested from donors with an average age of 52 years (range 27-80 year). One cross-sectional specimen of 5mm thickness was excised from the posterior-medial aspect of each meniscus. A meniscus loading stage was custom designed to subject meniscal cross-sections to incremental unconfined axial compression. Full-field strain distributions over the meniscus cross-section were acquired with an Electronic Speckle Pattern Interferometer (ESPI) system. ESPI in-plane strain reports were analyzed in terms of minimal principal (compressive) strain ~c. To asses the effect of age on strain distribution, specimens were stratified into a 'younger meniscus' group (n =4, 34±9 years), and an 'older meniscus' group (n=4, 71 ±6 years). Differences in ~c between the two groups were statistically analyzed with two-tailed Student t-tests at ~J, = 0.05. Results: Meniscus compression by 10 ~tm generated highly non-uniform strain distributions on cartilage cross-sections. After averaging ~c profiles along a line for all eight specimens, the highest strain of 0.29%±0.08% was found in the mid-region. The lowest strain of 0.04%±0.11% was found at the meniscus surface that articulates with the femoral condyle. Stratifying specimens in two age groups yielded up to 30% higher peak strain in the older meniscus group. Discussion: ESPI strain measurements quantified for the first time continuous, inhomogeneous strain distributions on meniscus cross-section. Our finding of higher compressive strain in the meniscus mid-region suggests that this section has a lower compressive modulus as compared to the surface region. We furthermore found that for older specimens, the strain elevation in the mid- region was more pronounced. 6416 We, 14:00-14:15 (P35) Validation and quantification of an in vivo model of functional bone adaptation C.J. MacKay 1, G.C. Goulet2, D.M.L. Cooper 3, D. Coombe4, R.E Zernicke2,5. 1McCaig Centre for Joint Injury and Arthritis Research, University of Calgary, Canada, 2Schulich School of Engineering, University of Calgary, Canada, 3Department of Orthopaedics, University of British Columbia, Vancouver, Canada, 4Cemputer Modelling Group, Ltd., Calgary, Alberta, Canada, 5Faculties of Kinesiology and Medicine, University of Calgary, Canada Interest in functional adaptation of bone over the past decades has led to the development of numerous experimental models [1-4]. While animal models provide insights into the molecular signaling pathways by which bone senses and adapts to changes in functional demand, there remains ambiguity about the mechanical components contributing to the principal determinants of skeletal morphology. Indeterminate characterization of the functional strain milieu imposed under some experimental loading protocols adds to the ambi- guity. Here, we used multiple triple-rosette and single-element strain gages, attached at a constant transverse plane, to measure the strain generated during a tibial cantilever bending protocol in skeletally mature female rats. Longitudinal normal strains were calculated at anterior, medial, and lateral gage sites. Three-dimensional geometry of the tibia was quantified via micro- computed tomography, which was then used as structural input for a finite element (FE) model. FE boundary conditions correlated with the in vive loading protocol. The mechanical environment acting across the tibial cross section was characterized by relating FE strains at the modelled gage sites to the calculated longitudinal normal strains. Locations of maximal compression, tension, and shear did not coincide with any of the individual gage sites, emphasizing the need for multiple rosette gages. By accurately quantifying the mechanical milieu produced during loading, the interpretation of the resultant osteogenic responses in this model will provide greater insight into the specific mechanical signals that influence dynamic skeletal morphology, as well as the cellular activities associated with mechanotransduction. References [1] Judex et al. J. Bone Min. Res. 1997; 12: 1737-1745. [2] Judex and Zernicke. J. Appl. Physiol. 2000; 88: 2183-2191. [3] Gross et al. J. Biomech. 1992; 25: 1081-1087. [4] Rubin and Lanyon. J. Orthop. Res. 1987; 5: 300-310.

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Page 1: Validation and quantification of an in vivo model of functional bone adaptation

Thread 4. Imaging

bone quality and to integrate automatic region of interest (ROI) algorithm in trabecular bone assessment in the region of interest (ROI). Method: Total of 34 human cadaver calcanei, age from 60 to 97 years old, are tested by SCAD, micro-CT and DEXA, as well as mechanical strength. An imaging recognition algorithm is developed, integrated in a newly developed SCAD system. The method is designed for the selection of an irregular ROI in SCAD determined ultrasound attenuation images from bone. When the ROI is automatically determined through programmed ROI seeding and neighboring 500 pixels, broadband ultrasound attenuation (BUA), and ultrasound velocity (UV) in the real body region are evaluated. The SCAD properties are then correlated to the bone mineral density (BMD), ~tCT volume fraction, and bone moduli. Results: Strong correlations have found between BMD (DEXA) and SCAD parameters, yielding R 2 =0.83 (BUA), and R 2 =0.65 (UV). Correlation between bone volume fraction and BUA shows R 2 =0.75, and shows R 2 =0.54 (UV). SCAD parameters predict the trabecular bone strength, in which correlation between BUA and elastic modulus is R2=0.54, and correlation between ultimate strength and BUA is R 2 =0.60. Discussion: These data have suggested that high resolution bone acous- tic images can be generated at particular ROI sites, e.g., calcaneus. Data have shown that ultrasound measurement significant correlate to ~tCT/DEXA determined bone architecture/density parameters, and particularly to bone's stiffness. These suggest that ultrasound imaging is capable to predict the quality of bone as a portable, noninvasive modality for applications in space and on Earth. Supported by the National Space Biomedical Research Institute (TD00207 & 00405) through NASA Cooperative Agreement NCC 9-58.

7222 We, 12:00-12:15 (P33) Prediction of the mechanical properties of normal and degenerated articular cartilage and trabecular bone using MRI

E. Lammentausta 1 , P. Kiviranta 1 , J. T6yr~s 2, M.T. Nieminen 3, J.S. Jurvelin 1,2. 1University of Kuopio, Kuopio, Finland, 2 Kuopio University Hospital, Kuopio, Finland, 3 0ulu University Hospital, Oulu, Finland

Structural properties of articular cartilage and mineral density (BMD) of tra- becular bone have been assessed by quantitative MRI methods, such as T2 and T2* mapping, respectively [1,2,3]. As bone and cartilage are usually assessed separately, the sequence of earliest tissue changes leading to osteoarthritis remains unknown. Aim of the present study was to determine interrelationships between the mechanical properties of articular cartilage and underlying trabecular bone, and to determine the ability of MRI parameters to quantitatively distinguish healthy and degenerated cartilage. Cadaveric human patellae (n=14, age=55±18) were investigated. From intact patellae, MRI parameters (cartilage T2, bone T2*) were obtained with a 1.5-T clinical scanner. As a reference, BMD was measured with pQCT. Elastic modulus was measured separately for cylindrical samples of cartilage [4] and underlying bone [5]. Mankin scores [6] of the cartilage samples were microscopically evaluated from blind-coded sections and the samples were divided into three groups, representing healthy tissue (Mankin score <3.3), early degeneration (3.3-5.0) and advanced degeneration (>5.0). Healthy samples showed significantly (p<0.05) higher moduli (cartilage 0.76±0.46 MPa vs. 0.28±0.55 MPa, bone 627±319 MPa vs. 325±164 MPa) and BMD (426±102mg/cm 3 vs. 336±105mg/cm3), and lower cartilage T2 (40±5 ms vs 49±8 ms) than samples with advanced degeneration. The linear correlations were significant between T2 and cartilage modulus (r=0.42, p < 0.01) and between BMD and bone modulus (r = 0.44, p < 0.01). However, elastic moduli of cartilage and bone were not significantly interrelated. T2* of bone showed no differences between the groups or correlation with elastic modulus. This study indicates that parallel changes take place in cartilage and bone during cartilage degeneration. However, further research with optimized MRI techniques is required to resolve detailed interrelationships of these changes.

References [1] Burstein D., Gray M.J. Bone Joint Surg Am. 2003; 85-A(Suppl 2): 70-7. [2] Grampp S, et al. Radiology 1996; 198: 213-218. [3] Wehrli FW, et al. Top Magn Reson Imaging 2002; 13: 335-35. [4] Jurvelin JS, et al. J Biomech 1997; 30: 235-241. [5] Turner CH, Burr DB. Bone 1993; 14: 595~08. [6] Mankin H J, et al. J Bone Joint Surg Am. 1971; 53: 523-537.

T4.7 Quantitative Functional Imaging $451

7140 We, 12:15-12:30 (P33) Characteristic strain distribution on meniscus cross-sections under axial compression

T. Augustin 1 , O. Kessler 2, M. Bottlang 1 . 1Biomechanics Laboratory, Legacy Research & Technology Center, Portland, Oregon; USA, 2 Stryker Europe, Thalwil, Switzerland.

Background: The meniscal ultra-structure is complex, being comprised of a highly oriented and non-homogeneous collagen fiber matrix which dominates its anisotropic behavior. This study aimed to deliver a functional character- ization of the complex meniscus structure using a novel laser-based strain mapping technique. Results of this study describe strain distributions on meniscus cross-sections under axial compression, as well as age-dependent changes thereof. Methods: Eight human medial menisci were harvested from donors with an average age of 52 years (range 27-80 year). One cross-sectional specimen of 5mm thickness was excised from the posterior-medial aspect of each meniscus. A meniscus loading stage was custom designed to subject meniscal cross-sections to incremental unconfined axial compression. Full-field strain distributions over the meniscus cross-section were acquired with an Electronic Speckle Pattern Interferometer (ESPI) system. ESPI in-plane strain reports were analyzed in terms of minimal principal (compressive) strain ~c. To asses the effect of age on strain distribution, specimens were stratified into a 'younger meniscus' group (n =4, 3 4 ± 9 years), and an 'older meniscus' group (n=4, 71 ± 6 years). Differences in ~c between the two groups were statistically analyzed with two-tailed Student t-tests at ~J, = 0.05. Results: Meniscus compression by 10 ~tm generated highly non-uniform strain distributions on cartilage cross-sections. After averaging ~c profiles along a line for all eight specimens, the highest strain of 0.29%±0.08% was found in the mid-region. The lowest strain of 0.04%±0.11% was found at the meniscus surface that articulates with the femoral condyle. Stratifying specimens in two age groups yielded up to 30% higher peak strain in the older meniscus group. Discussion: ESPI strain measurements quantified for the first time continuous, inhomogeneous strain distributions on meniscus cross-section. Our finding of higher compressive strain in the meniscus mid-region suggests that this section has a lower compressive modulus as compared to the surface region. We furthermore found that for older specimens, the strain elevation in the mid- region was more pronounced.

6416 We, 14:00-14:15 (P35) Validation and quantification of an in vivo model of functional bone adaptation

C.J. MacKay 1 , G.C. Goulet 2, D.M.L. Cooper 3, D. Coombe 4, R.E Zernicke 2,5. 1McCaig Centre for Joint Injury and Arthritis Research, University of Calgary, Canada, 2 Schulich School of Engineering, University of Calgary, Canada, 3Department of Orthopaedics, University of British Columbia, Vancouver, Canada, 4Cemputer Modelling Group, Ltd., Calgary, Alberta, Canada, 5Faculties of Kinesiology and Medicine, University of Calgary, Canada

Interest in functional adaptation of bone over the past decades has led to the development of numerous experimental models [1-4]. While animal models provide insights into the molecular signaling pathways by which bone senses and adapts to changes in functional demand, there remains ambiguity about the mechanical components contributing to the principal determinants of skeletal morphology. Indeterminate characterization of the functional strain milieu imposed under some experimental loading protocols adds to the ambi- guity. Here, we used multiple triple-rosette and single-element strain gages, attached at a constant transverse plane, to measure the strain generated during a tibial cantilever bending protocol in skeletally mature female rats. Longitudinal normal strains were calculated at anterior, medial, and lateral gage sites. Three-dimensional geometry of the tibia was quantified via micro- computed tomography, which was then used as structural input for a finite element (FE) model. FE boundary conditions correlated with the in vive loading protocol. The mechanical environment acting across the tibial cross section was characterized by relating FE strains at the modelled gage sites to the calculated longitudinal normal strains. Locations of maximal compression, tension, and shear did not coincide with any of the individual gage sites, emphasizing the need for multiple rosette gages. By accurately quantifying the mechanical milieu produced during loading, the interpretation of the resultant osteogenic responses in this model will provide greater insight into the specific mechanical signals that influence dynamic skeletal morphology, as well as the cellular activities associated with mechanotransduction.

References [1] Judex et al. J. Bone Min. Res. 1997; 12: 1737-1745. [2] Judex and Zernicke. J. Appl. Physiol. 2000; 88: 2183-2191. [3] Gross et al. J. Biomech. 1992; 25: 1081-1087. [4] Rubin and Lanyon. J. Orthop. Res. 1987; 5: 300-310.