Next Generation Biometrics for the Modeling and Detection of Early Soft Tissue Degeneration in Vivo

Soft tissue degeneration, a leading cause of physical pain and disability, is highly prevalent in articular cartilage and intervertebral discs (IVDs). The interplay of collagen and proteoglycans with interstitial fluid, which provides structured load support, can begin to degrade due to trauma or overuse, often leading debilitating pain. Detection of soft tissue degeneration at its earliest stage is paramount, as the degeneration is an ever-worsening positive feedback loop. Conventional magnetic resonance imaging (MRI), an ideal modality for early detection and prediction of soft tissue degeneration, is limited by a lack of specificity to individual components, an inability to analyze functional changes, and a weak correlation between quantitative MRI (qMRI) metrics and early tissue degeneration.

In this thesis, the enhancement of MRI metric sensitivity to in vivo tissue state is investigated by improving sensitivity of structural variation detection, spatially assessing soft tissue function, and creating a novel biomarker for the analysis of structural and functional imaging data. Chapters 1 and 2 cover the necessary anatomy and physiology and MRI fundamentals for the following chapters. Chapter 3 explores the use of a stretched exponential (SE) model to improve sensitivity to structural variations. The SE form shows promise in distinguishing between healthy intervertebral discs (IVDs) of varying location, improving on conventional MRI metrics. Chapter 4 details the first in vivo study of IVD intratissue strain laying the groundwork for future diseased model work. The functional assessment of soft tissue would allow for the detection of intratissue biomechanical changes that accompany the structural variations in soft tissue degeneration. In Chapters 5 and 6, the use of a new biometric, anatomically relevant spatial gradients, is explored with the aim of improving the correlations between structural and functional qMRI data and tissue health. Utilizing the digital nature of MRI data and finite difference methods, the new biometric shows stronger correlations to disease state and can be applied across various different tissues.

The results presented in this thesis have improved the use of MRI as a tool for modeling, detection, and prediction of soft tissue degeneration.

Year	Entry
1982	Armstrong CG, Mow VC. Variations in the intrinsic mechanical properties of human articular cartilage with age, degeneration, and water content. J Bone Joint Surg. 1982;64A(1):88-94.
1983	Muir H. Proteoglycans as organizers of the intercellular matrix. Biochem Soc Trans. December 1983;11(6):613-622.
1988	Urban JPG, McMullin JF. Swelling pressure of the lumbar intervertebral discs influence of age, spinal level, composition, and degeneration. Spine. February 1988;13(2):179-187.
2006	Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine. August 15, 2006;31(18):2151-2161.
2008	Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: part II. Arthritis Rheum. January 2008;58(1):26-35.
2005	Mow VC, Huiskes R, eds. Basic Orthopaedic Biomechanics & Mechano-Biology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
1990	Thompson JP, Pearce RH, Schechter MT, Adams ME, Tsang IK, Bishop PB. Preliminary evaluation of a scheme for grading the gross morphology of the human intervertebral disc. Spine. May 1990;15(5):411-415.
1996	Antoniou J, Steffen T, Nelson F, Winterbottom N, Hollander AP, Poole RA, Aebi M, Alini M. The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. J Clin Invest. August 15, 1996;98(4):996-1003.
1968	Maroudas A, Bullough P. Permeability of articular cartilage. Nature. September 21, 1968;219(5160):1260-1261.
1992	Hardingham TE, Fosang AJ. Proteoglycans: many forms and many functions. FASEB J. February 1992;6(3):861-870.
2002	Yeh W-C, Li P-C, Jeng Y-M, Hsu H-C, Kuo P-L, Li M-L, Yang P-M, Lee PH. Elastic modulus measurements of human liver and correlation with pathology. Ultrasound Med Biol. April 2002;28(4):467-474.
1998	Iatridis JC, Setton LA, Foster RJ, Rawlins BA, Weidenbaum M, Mow VC. Degeneration affects the anisotropic and nonlinear behaviors of human anulus fibrosus in compression. J Biomech. June 1998;31(6):535-544.
1984	Armstrong CG, Lai WM, Mow VC. An analysis of the unconfined compression of articular cartilage. J Biomech Eng. May 1984;106(2):165-173.
2000	Race A, Broom ND, Robertson P. Effect of loading rate and hydration on the mechanical properties of the disc. Spine. March 15, 2000;25(6):662-669.
2003	Wong M, Carter DR. Articular cartilage functional histomorphology and mechanobiology: a research perspective. Bone. July 2003;33(1):1-13.
1998	Lotz JC, Colliou OK, Chin JR, Duncan NA, Liebenberg E. Compression-induced degeneration of the intervertebral disc: an in vivo mouse model and finite-element study. Spine. December 1, 1998;23(23):2493-2506.
1984	Myers ER, Lai WM, Mow VC. A continuum theory and an experiment for the ion-induced swelling behavior of articular cartilage. J Biomech Eng. May 1984;106(2):151-158.
1993	Shapiro F, Koide S, Glimcher MJ. Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J Bone Joint Surg. April 1993;75A(4):532-553.
1997	Iatridis JC, Setton LA, Weidenbaum M, Mow VC. Alterations in the mechanical behavior of the human lumbar nucleus pulposus with degeneration and aging. J Orthop Res. March 1997;15(2):318-322.
1986	Hodge WA, Fijan RS, Carlson KL, Burgess RG, Harris WH, Mann RW. Contact pressures in the human hip joint measured in vivo. Proc Natl Acad Sci USA. May 1986;83(9):2879-2883.
1999	Iatridis JC, Mente PL, Stokes IAF, Aronsson DD, Alini M. Compression-induced changes in intervertebral disc properties in a rat tail model. Spine. May 15, 1999;24(10):996-1002.
2008	Raj PP. Intervertebral disc: anatomy-physiology-pathophysiology-treatment. Pain Pract. January–February 2008;8(1):18-44.
1987	Pearce RH, Grimmer BJ, Adams ME. Degeneration and the chemical composition of the human lumbar intervertebral disc. J Orthop Res. 1987;5(2):198-205.
1994	Best BA, Guilak F, Setton LA, Zhu W, Saed-Nejad F, Ratcliffe A, Weidenbaum M, Mow VC. Compressive mechanical properties of the human anulus fibrosus and their relationship to biochemical composition. Spine. January 15, 1994;19(2):212-221.
2006	Pritzker KPH, Gay S, Jimenez SA, Ostergaard K, Pelletier J-P, Revell PA, Salter D, van den Berg WB. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage. January 2006;14(1):13-29.
1981	Lyons G, Eisenstein SM, Sweet MBE. Biochemical changes in intervertebral disc degeneration. Biochim Biophys Acta. 1981;673:443-453.
1995	Drost MR, Willems P, Snijders H, Huyghe JM, Janssen JD, Huson A. Confined compression of canine annulus fibrosus under chemical and mechanical loading. J Biomech Eng. November 1995;117(4):390-396.
1998	Gu WY, Lai WM, Mow VC. A mixture theory for charged-hydrated soft tissues containing multi-electrolytes: passive transport and swelling behaviors. J Biomech Eng. April 1998;120(2):169-180.
2009	Fox AJS, Bedi A, Rodeo SA. The basic science of articular cartilage: structure, composition, and function. Sports Health. November–December 2009;1(6):461-468.
1995	Buckwalter JA. Aging and degeneration of the human intervertebral disc. Spine. June 1995;20(11):1307-1314.

Year

Entry

1982

Armstrong CG, Mow VC. Variations in the intrinsic mechanical properties of human articular cartilage with age, degeneration, and water content. J Bone Joint Surg. 1982;64A(1):88-94.

1983

Muir H. Proteoglycans as organizers of the intercellular matrix. Biochem Soc Trans. December 1983;11(6):613-622.

1988

Urban JPG, McMullin JF. Swelling pressure of the lumbar intervertebral discs influence of age, spinal level, composition, and degeneration. Spine. February 1988;13(2):179-187.

2006

Adams MA, Roughley PJ. What is intervertebral disc degeneration, and what causes it? Spine. August 15, 2006;31(18):2151-2161.

2008

Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG, Jordan JM, Katz JN, Kremers HM, Wolfe F; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: part II. Arthritis Rheum. January 2008;58(1):26-35.