Development of an Image-Based System for Assessment of Bone Density, Geometry, and Micro-Architecture Suitable for Human Studies

Osteoporosis is a common age-related disease characterized by reduced bone mineral density (BMD), micro-structural deterioration, and enhanced fracture-risk. There is compelling evidence that bone micro-structural properties are strong determinants of bone strength and fracture-risk. Valid and reliable measures of effective trabecular bone (Tb) micro-structural features are of paramount significance in early detection of osteoporosis and accurate assessment of fracture-risk. It has been shown using biomechanical modelling that transverse trabeculae are important players in arresting the buckling of longitudinal trabeculae that causes compressive fractures. One of the aims of my PhD research was to develop and validate a new method of characterizing transverse and longitudinal trabeculae at in vivo imaging resolution and retrospectively examine its application using existing human study data. A set of cadaveric ankle specimens (n = 19) were collected, prepared, and scanned using CT and micro-CT imaging protocols, to validate new methods.

Emerging in vivo imaging technologies allow us to collect bone data at the hip. A major challenge in this research approach is related to selection of standardized anatomic ROIs in hip scans of individual subjects. The second aim of my PhD research was to develop and validate an active-shape-model (ASM) based method to automatically generate anatomically standardized ROIs that will adjust for subject-specific variations in femur geometry and shape. Also, the ASM may be used to compute effective geometric features from individual femur shape instances. To overcome the challenges of building the ASM of the complex three-dimensional (3-D) shape of the femur, a novel geodesic-editor graphical-user-interface (GUI) has been designed and developed that allows drawing and manipulating lines and landmarks on arbitrary curved surfaces as compared to 2-D planes used by conventional GUIs. Also, a new theory and algorithm of shape- based smoothing have been developed to smooth image-based femur shape and reduce digital artifacts.

The third aim of my PhD research program was to develop a comprehensive manual quality control protocol for quantitative in vivo bone micro-structural imaging cascades for human studies. The purpose of this aim is to identify and resolve failure points in the large and complex image processing protocol for quantitative in vivo bone micro-structural imaging, developed in our laboratory, which uses several study-specific assumptions to optimize and automate the overall computational system.

Year	Entry
2006	Khosla S, Riggs BL, Atkinson EJ, Oberg AL, McDaniel LJ, Holets M, .Peterson JM, Melton LJ III. Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. J Bone Miner Res. January 2006;21(1):124-131.
1996	Saha PK, Chaudhuri BB. 3D digital topology under binary transformation with applications. Comput Vis Image Und. May 1996;63(3):418-429.
1997	Saha PK, Chaudhuri BB, Dutta Majumder D. A new shape preserving parallel thinning algorithm for 3D digital images. Patt Recogn. December 1997;30(2):1939-1955.
2021	Saha PK, Oweis RR, Zhang X, Letuchy E, Eichenberger-Gilmore JM, Burns TL, Warren JJ, Janz KF, Torner JC, Snetselaar LG, Levy SM. Effects of fluoride intake on cortical and trabecular bone microstructure at early adulthood using multi-row detector computed tomography (MDCT). Bone. May 2021;146:115882.
1997	Silva MJ, Gibson LJ. Modeling the mechanical behavior of vertebral trabecular bone: effects of age-related changes in microstructure. Bone. 1997;21(2):191-199.
2002	Wehrli F, Saha P, Gomberg B, Song H, Snyder P, Benito M, Wright A, Weening R. Role of magnetic resonance for assessing structure and function of trabecular bone. Top Magn Reson Imaging. October 2002;13(5):335-355.
2001	Wehrli FW, Gomberg BR, Saha PK, Song HK, Hwang SN, Snyder PJ. Digital topological analysis of in vivo magnetic resonance microimages of trabecular bone reveals structural implications of osteoporosis. J Bone Miner Res. October 2001;16(8):1520-1531.
2001	Hernandez CJ, Beaupré GS, Keller TS, Carter DR. The influence of bone volume fraction and ash fraction on bone strength and modulus. Bone. July 2001;29(1):74-78.
2000	Saha PK, Gomberg BR, Wehrli FW. Three-dimensional digital topological characterization of cancellous bone architecture. Int J Imaging Syst Technol. 2000;11(1):81-90.
1985	Kleerekoper M, Villanueva AR, Stanciu J, Rao DS, Parfitt AM. The role of three-dimensional trabecular microstructure in the pathogenesis of vertebral compression fractures. Calcif Tiss Int. 1985;37(6):594-597.
2005	Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab. December 2005;90(12):6508-6515.
1992	Cooper C, Campion G, Melton LJ III. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. November 1992;2(6):285-289.
1997	Hildebrand T, Rüegsegger P. Quantification of bone microarchitecture with the structure model index. Comput Methods Prog Biomed. 1997;1(1):15-23.
1992	Hahn M, Vogel M, Pompesius-Kempa M, Delling G. Trabecular bone pattern factor: a new parameter for simple quantification of bone microarchitecture. Bone. 1992;13(4):327-330.
1988	Melton LJ III. Epidemiology of fractures. In: Riggs BL, Melton LJ III, eds. Osteoporosis: Etiology, Diagnosis, and Management. New York, NY: Raven Press; 1988:133-154.
2020	Bon J, Nouraie SM, Smith KJ, Dransfield MT, McDonald M, Hoffman EA, Newell JD Jr, Comellas AP, Saha PK, Bowler RP, Regan EA. Lung‐specific risk factors associated with incident hip fracture in current and former smokers. J Bone Miner Res. October 2020;35(10):1952-1961.
1998	Link TM, Majumdar S, Augat P, Lin JC, Newitt D, Lu Y, Lane NE, Genant HK. In vivo high resolution MRI of the calcaneus: differences in trabecular structure in osteoporosis patients. J Bone Miner Res. July 1998;13(7):1175-1182.
1989	Vesterby A, Gundersen H, Melsen F. Star volume of marrow space and trabeculae of the first lumbar vertebra: sampling efficiency and biological variation. Bone. 1989;10(1):7-13.
2006	Stauber M, Müller R. Volumetric spatial decomposition of trabecular bone into rods and plates: a new method for local bone morphometry. Bone. 2006;38(4):475-484.
2016	Chen C. Mechanical and Micro-Structural Modeling of Trabecular Bone by in Vivo Imaging [PhD thesis]. University of Iowa; December 2016.
2008	Liu XS, Sajda P, Saha PK, Wehrli FW, Bevill G, Keaveny TM, Guo XE. Complete volumetric decomposition of individual trabecular plates and rods and its morphological correlations with anisotropic elastic moduli in human trabecular bone. J Bone Miner Res. February 2008;23(2):223-235.
2002	Cummings SR, Melton LJ III. Epidemiology and outcomes of osteoporotic fractures. Lancet. May 18, 2002;359(9319):1761-1767.
1989	Feldkamp LA, Goldstein SA, Parfitt MA, Jesion G, Kleerekoper M. The direct examination of three‐dimensional bone architecture in vitro by computed tomography. J Bone Miner Res. 1989;4(1):3-11.
2006	Liu XS, Sajda P, Saha PK, Wehrli FW, Guo XE. Quantification of the roles of trabecular microarchitecture and trabecular type in determining the elastic modulus of human trabecular bone. J Bone Miner Res. October 2006;21(10):1608-1617.
1996	Majumdar S, Newitt D, Mathur A, Osman D, Gies A, Chiu E, Lotz J, Kinney J, Genant H. Magnetic resonance imaging of trabecular bone structure in the distal radius: relationship with X-ray tomographic microscopy and biomechanics. Osteoporos Int. September 1996;6(5):376-385.
2006	Seeman E, Delmas PD. Bone quality: the material and structural basis of bone strength and fragility. NEJM. May 25, 2006;354(21):2250-2261.
2008	Boyd SK. Site-specific variation of bone micro-architecture in the distal radius and tibia. J Clin Densitom. July–September 2008;11(3):424-430.
1992	Melton LJ III, Chrischilles EA, Cooper C, Lane AW, Riggs BL. How many women have osteoporosis? J Bone Miner Res. September 1992;7(9):1005-1010.
2010	Liu XS, Cohen A, Shane E, Stein E, Rogers H, Kokolus SL, Yin PT, McMahon DJ, Lappe JM, Recker RR, Guo XE. Individual trabeculae segmentation (ITS)–based morphological analysis of high‐resolution peripheral quantitative computed tomography images detects abnormal trabecular plate and rod microarchitecture in premenopausal women with idiopathic osteoporosis. J Bone Miner Res. July 2010;25(7):1496-1505.
2002	Riggs BL, Melton LJ III. Bone turnover matters: the raloxifene treatment paradox of dramatic decreases in vertebral fractures without commensurate increases in bone density. J Bone Miner Res. January 2002;17(1):11-14.
1993	Recker RR. Architecture and vertebral fracture. Calcif Tiss Int. 1993;53(suppl 1):S139-S142.
2012	Liu XS, Stein EM, Zhou B, Zhang CA, Nickolas TL, Cohen A, Thomas V, McMahon DJ, Cosman F, Nieves J, Shane E, Guo XE. Individual trabecula segmentation (ITS)‐based morphological analyses and microfinite element analysis of HR‐pQCT images discriminate postmenopausal fragility fractures independent of DXA measurements. J Bone Miner Res. February 2012;27(2):263-272.

Year

Entry

2006

Khosla S, Riggs BL, Atkinson EJ, Oberg AL, McDaniel LJ, Holets M, .Peterson JM, Melton LJ III. Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. J Bone Miner Res. January 2006;21(1):124-131.

1996

Saha PK, Chaudhuri BB. 3D digital topology under binary transformation with applications. Comput Vis Image Und. May 1996;63(3):418-429.

1997

Saha PK, Chaudhuri BB, Dutta Majumder D. A new shape preserving parallel thinning algorithm for 3D digital images. Patt Recogn. December 1997;30(2):1939-1955.

2021

Saha PK, Oweis RR, Zhang X, Letuchy E, Eichenberger-Gilmore JM, Burns TL, Warren JJ, Janz KF, Torner JC, Snetselaar LG, Levy SM. Effects of fluoride intake on cortical and trabecular bone microstructure at early adulthood using multi-row detector computed tomography (MDCT). Bone. May 2021;146:115882.

1997

Silva MJ, Gibson LJ. Modeling the mechanical behavior of vertebral trabecular bone: effects of age-related changes in microstructure. Bone. 1997;21(2):191-199.