Biochemical (and Functional) Imaging of Articular Cartilage

Martha L. Gray; Deborah Burstein; Yang Xia

doi:10.1055/s-2001-19043

Seminars in Musculoskeletal Radiology, Table of Contents

Semin Musculoskelet Radiol 2001; 05(4): 329-344
DOI: 10.1055/s-2001-19043

Biochemical (and Functional) Imaging of Articular Cartilage

Martha L. Gray¹ , Deborah Burstein² , Yang Xia³

¹Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge MA; New England Baptist Bone and Joint Center, Boston MA
²Harvard-MIT Division of Health Sciences and Technology, Cambridge MA; New England Baptist Bone and Joint Center, Boston MA; Department of Radiology, Beth Israel, Boston MA
³Department of Physics and Center for Biomedical Research, Oakland University, Rochester, MI

Abstract

ABSTRACT

Over the coming decades nondestructive biochemical imaging by magnetic resonance imaging (MRI) will provide an adjunct or surrogate for the destructive histologic and biochemical assays used today. A number of MRI methods demonstrate image contrast that, although influenced by the biochemical composition, is not normally specific to a particular measure of the biochemical state. The most widely used of these is T2-weighted imaging, which variably reveals collagen ultrastructure, hydration (or collagen content), and, to a lesser extent, glycosaminoglycan (GAG) concentration (each of these biochemical metrics is an important determinant of the functional integrity of cartilage). The lack of specificity of this technique (and others discussed herein) confounds efforts to improve strategies for evaluating cartilage. However, three methods permit a very specific measure of the cartilage biochemical state. Each of these three methods, explored in detail in this article, is rooted in a biophysical theory that relates the image signal intensity to a specific biochemical feature. Proton-density imaging directly measures water content (hydration), a parameter that might increase approximately 5% with significant degeneration. Magic-angle imaging, in which the angle dependence of T2 is measured, can provide a specific measure of collagen (or macromolecular) ultrastructure. The difficulty in getting the angle dependence presently precludes its use clinically. Delayed gadolinium-enhanced MRI of cartilage provides a specific measure of the distribution of GAGs. This method measures the distribution of a charged contrast agent, which in turn reflects the distribution of charge associated with GAG. This technique can be used in a clinical setting, and ongoing studies will explore its utility in monitoring therapeutic efficacy and disease progression. Although none of these techniques are presently in routine clinical use, emerging data provide promise that the future will see patient-specific biochemical analysis of cartilage, an outcome almost unimaginable 20 years ago.

KEYWORD

Cartilage - articular/chemistry/pathology - collagen/chemistry - proteoglycan/glycosaminoglycan - gadolinium DTPA - magnetic resonance imaging/methods - osteoarthritis/diagnosis

Full Text

References

REFERENCES

1 Freeman M. Adult Articular Cartilage. Freeman M, ed. London: Pitman Medical; 1979
2 Pelletier J P, Martel-Pelletier J, Howell D S. Etiopathogenesis of osteoarthritis. In: Koopman WJ, ed. Arthritis and Allied Conditions: A Textbook of Rheumatology Philadelphia: Lippincott, Williams & Wilkins 2000: 2195-2245
3 Nuki G. Role of mechanical factors in the aetiology, pathogenesis and progression of osteoarthritis. In: Reninster JY, Pelletier JP, Martel-Pelletier J, Henrotin Y, eds. Osteoarthritis: Clinical and Experimental aspects Berlin: Springer-Verlag 1999: 101-114
4 Poole A R. Cartilage in health and disease. In: Koopman W, ed. Arthritis and Allied Conditions Baltimore: Williams & Wilkins 1997: 255-308
5 Kempson G, Muir H, Swanson S, Freeman M. Correlations between stiffness and the chemical constituents of cartilage on the femoral head. Biochimica et Biophysica Acta . 1976; 428 741-746
6 Treppo S, Koepp H, Quan E C, Cole A A, Kuettner K E, Grodzinsky A J. Comparison of biomechanical and biochemical properties of cartilage from human knee and ankle pairs. J Orthop Res . 2000; 18 739-748
7 Jurvelin J S, Arokoski J P, Hunziker E B, Helminen H J. Topographical variation of the elastic properties of articular cartilage in the canine knee. J Biomech . 2000; 33 669-675
8 Guilak F, Ratcliffe A, Lane N, Rosenwasser M P, Mow V C. Mechanical and biochemical changes in the superficial zone of articular cartilage in canine experimental osteoarthritis. J Orthop Res . 1994; 12 474-484
9 Roberts S, Weightman B, Urban J, Chappell D. Mechanical and biochemical properties of human articular cartilage in osteoarthritic femoral heads and in autopsy specimens. J Bone Joint Surg Br . 1986; 68 278-288
10 Hoch D H, Grodzinsky A J, Koob T J, Albert M L, Eyre D R. Early changes in material properties of rabbit articular cartilage after meniscectomy. J Orthop Res . 1983; 1 4-12
11 Armstrong C G, Mow V C. Variations in the intrinsic mechanical properties of human articular cartilage with age, degeneration, and water content. J Bone Joint Surg Am . 1982; 64 88-94
12 Allen R G. Mechanical properties of selectively degraded cartilage explants; correlation to the spaciotemporal distribution of glycosaminoglycans. S.M. published thesis Mechanical Engineering. Cambridge: MIT 1996
13 Grodzinsky A J. Electromechanical and physicochemical properties of connective tissue. Crit Rev Biomed Eng . 1983; 9 133-199
14 Buckwalter J A, Martin J. Degenerative joint disease. Clin Symp . 1995; 47 1-32
15 Maroudas A I. Balance between swelling pressure and collagen tension in normal and degenerate cartilage. Nature . 1976; 260 808-809
16 Venn M, Maroudas A. Chemical composition and swelling of normal and osteoarthrotic femoral head cartilage. I. Chemical composition. Ann Rheum Dis . 1977; 36 121-129
17 Billinghurst R C, Dahlberg L, Ionescu M. Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. J Clin Invest . 1997; 99 1534-1545
18 Dodge G R, Pidoux I, Poole A R. The degradation of type II collagen in rheumatoid arthritis: an immunoelectron microscopic study. Matrix . 1991; 11 330-338
19 Hollander A P, Heathfield T F, Webber C. Increased damage to type II collagen in osteoarthritic articular cartilage detected by a new immunoassay. J Clin Invest . 1994; 93 1722-1732
20 Hollander A P, Pidoux I, Reiner A, Rorabeck C, Bourne R, Poole A R. Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration. J Clin Invest . 1995; 96 2859-2869
21 Bank R A, Krikken M, Beekman B. A simplified measurement of degraded collagen in tissues: application in healthy, fibrillated and osteoarthritic cartilage. Matrix Biol . 1997; 16 233-243
22 Chen M H, Broom N. On the ultrastructure of softened cartilage: a possible model for structural transformation. J Anat . 1998; 192 329-341
23 Eisenberg S R, Grodzinsky A J. Swelling of articular cartilage and other connective tissues: electromechanochemical forces. J Orthop Res . 1985; 3 148-159
24 Frank E H, Grodzinsky A J. Cartilage electromechanics, I. Electrokinetic transduction and the effects of electrolyte pH and ionic strength. J Biomech . 1987; 20 615-627
25 Hohe J, Faber S, Stammberger T, Reiser M, Englmeier K H, Eckstein F. A technique for 3D in vivo quantification of proton density and magnetization transfer coefficients of knee joint cartilage. Osteoarth Cartil . 2000; 8 426-433
26 Xia Y. Relaxation anisotropy in cartilage by NMR microscopy (μMRI) at 14-micron resolution. Magn Reson Med . 1998; 39 941-949
27 Xia Y, Moody J B, Burton-Wurster N, Lust G. Quantitative in situ correlation between microscopic MRI and polarized light microscopy studies of articular cartilage. Osteoarth Cartil . 2001; 9 393-406
28 Lesperance L M, Gray M L, Burstein D. Determination of fixed charge density in cartilage using nuclear magnetic resonance. J Orthop Res . 1992; 10 1-13
29 Bashir A, Gray M L, Hartke J, Burstein D. Nondestructive imaging of human cartilage glycosaminoglycan concentration by MRI. Magn Reson Med . 1999; 41 857-865
30 Insko E K, Reddy R, Leigh J S. High resolution, short echo time sodium imaging of articular cartilage. J Magn Reson Imag . 1997; 7 1056-1059
31 Reddy R, Insko E K, Noyszewski E A, Dandora R, Kneeland J B, Leigh J S. Sodium MRI of human articular cartilage in vivo. Magn Reson Med . 1998; 39 697-701
32 Granot J. Sodium imaging of human body organs and extremities in vivo. Radiology . 1988; 167 547-550
33 Regatte R R, Kaufman J H, Noyszewski E A, Reddy R. Sodium and proton MR properties of cartilage during compression. J Magn Reson Imag . 1999; 10 961-967
34 Shapiro E M, Borthakur A, Dandora R, Kriss A, Leigh J S, Reddy R. Sodium visibility and quantitation in intact bovine articular cartilage using high field (23)Na MRI and MRS. J Magn Reson . 2000; 142 24-31
35 Jelicks L A, Paul P K, O'Byrne E, Gupta R K. Hydrogen-1, sodium-23, and carbon-13 MR spectroscopy of cartilage degradation in vitro. J Magn Reson Imag . 1993; 3 565-568
36 Bashir A. Sodium NMR relaxation parameters in cartilage: implications for MR imaging. S.M. Thesis. Electrical engineering and computer science Cambridge: MIT, 1995: 134
37 Bashir A, Gray M L, Burstein D. Gd-DTPA2- as a measure of cartilage degradation. Magn Reson Med . 1996; 36 665-673
38 Bashir A, Gray M L, Boutin R D, Burstein D. Glycosaminoglycan in articular cartilage: in vivo assessment with delayed Gd(DTPA)(2-)-enhanced MR imaging. Radiology . 1997; 205 551-558
39 Trattnig S, Mlynarik V, Breitenseher M. MRI visualization of proteoglycan depletion in articular cartilage via intravenous administration of Gd-DTPA. Magn Reson Imag . 1999; 17 577-583
40 Allen R G, Burstein D, Gray M L. Monitoring glycosaminoglycan replenishment in cartilage explants with gadolinium-enhanced magnetic resonance imaging. J Orthop Res . 1999; 17 430-436
41 Xia Y. Magic-angle effect in magnetic resonance imaging of articular cartilage: a review. Invest Radiol. 2000a; 35 602-621
42 Grunder W, Wagner M, Werner A. MR-microscopic visualization of anisotropic internal cartilage structures using the magic angle technique. Magn Reson Med . 1998; 39 376-382
43 Goodwin D W, Wadghiri Y Z, Dunn J F. Micro-imaging of articular cartilage: T2, proton density, and the magic angle effect. Acad Radiol . 1998; 5 790-798
44 Foster J E, Maciewicz R A, Taberner J. Structural periodicity in human articular cartilage: comparison between magnetic resonance imaging and histological findings. Osteoarth Cart . 1999; 7 480-485
45 Dardzinski B J, Mosher T J, Li S, Van Slyke A M, Smith M B. Spatial variation of T2 in human articular cartilage. Radiology . 1997; 205 546-550
46 Fragonas E, Mlynarik V, Jellus V. Correlation between biochemical composition and magnetic resonance appearance of articular cartilage. Osteoarth Cartil . 1998; 6 24-32
47 Weidenbaum M, Foster R J, Best B A. Correlating magnetic resonance imaging with the biochemical content of the normal human intervertebral disc. J Orthop Res . 1992; 10 552-561
48 Goodwin D W, Dunn J F. High-resolution magnetic resonance imaging of articular cartilage: correlation with histology and pathology. Top Magn Reson Imaging . 1998; 9 337-347
49 Gahunia H K, Lemaire C, Babyn P S, Cross A R, Kessler M J, Pritzker K P. Osteoarthritis in rhesus macaque knee joint: quantitative magnetic resonance imaging tissue characterization of articular cartilage. J Rheumatol . 1995; 22 1747-1756
50 Watrin A, Ruaud J P, Olivier P T. T2 mapping of rat patellar cartilage. Radiology . 2001; 219 395-402
51 Antoniou J, Pike G B, Steffen T. Quantitative magnetic resonance imaging in the assessment of degenerative disc disease. Magn Reson Med . 1998; 40 900-907
52 Liu A K. The dependence of NMR-measured diffusion, magnetization transfer, and T2 relaxation on fractional water content in bovine articular cartilage. Thesis. Electr Eng Comput Sci Cambridge: MIT 1995
53 Burstein D, Bashir A, Gray M L. MRI techniques in early stages of cartilage disease. Invest Radiol . 2000; 35 622-638
54 Lusse S, Claassen H, Gehrke T. Evaluation of water content by spatially resolved transverse relaxation times of human articular cartilage. Magn Reson Imaging . 2000; 18 423-430
55 Kim D K, Ceckler T L, Hascall V C, Calabro A, Balaban R S. Analysis of water-macromolecule proton magnetization transfer in articular cartilage. Magn Reson Med . 1993; 29 211-215
56 Seo G S, Aoki J, Moriya H. Hyaline cartilage: in vivo and in vitro assessment with magnetization transfer imaging. Radiology . 1996; 201 525-530
57 Gray M L, Burstein D, Lesperance L M, Gehrke L. Magnetization transfer in cartilage and its constituent macromolecules. Magn Reson Med . 1995; 34 319-325
58 Wachsmuth L, Juretschke H P, Raiss R X. Can magnetization transfer magnetic resonance imaging follow proteoglycan depletion in articular cartilage?. Magma . 1997; 5 71-78
59 Potter K, Butler J J, Horton W E, Spencer R G. Response of engineered cartilage tissue to biochemical agents as studied by proton magnetic resonance microscopy. Arthritis Rheum . 2000; 43 1580-1590
60 Bageac A C, Gray M L, Zhang M, Poole A R, Burstein D. Development of an MRI surrogate for immunohistochemical staining of collagen damage in cartilage. 5th International conference on magnetic resonance microscopy. Heidelberg, Germany; 1999
61 Hsu E W, Setton L A. Diffusion tensor microscopy of the intervertebral disc anulus fibrosus. Magn Reson Med . 1999; 41 992-999
62 Duvvuri U, Reddy R, Patel S D, Kaufman J H, Kneeland J B, Leigh J S. T1 rho-relaxation in articular cartilage: effects of enzymatic degradation. Magn Reson Med . 1997; 38 863-867
63 Duvvuri U, Charagundla S R, Kudchodkar S B. Human knee: in vivo t1(rho)-weighted mr imaging at 1.5 t preliminary experience. Radiology . 2001; 220 822-826
64 Mlynarik V, Trattnig S, Huber M, Zembsch A, Imhof H. The role of relaxation times in monitoring proteoglycan depletion in articular cartilage. J Magn Reson Imag . 1999; 10 497-502
65 Lehner K B, Rechl H P, Gmeinwieser J K, Heuck A F, Lukas H P, Kohl H P. Structure, function, and degeneration of bovine hyaline cartilage: assessment with MR imaging in vitro. Radiology . 1989; 170 495-499
66 Hayes C W, Sawyer R W, Conway W F. Patellar cartilage lesions: in vitro detection and staging with MR imaging and pathologic correlation. Radiology . 1990; 176 479-483
67 Modl J M, Sether L A, Haughton V M, Kneeland J B. Articular cartilage: correlation of histologic zones with signal intensity at MR imaging. Radiology . 1991; 181 853-855
68 Rubenstein J D, Kim J K, Morova-Protzner I, Stanchev P L, Henkelman R M. Effects of collagen orientation on MR imaging characteristics of bovine articular cartilage. Radiology . 1993; 188 219-226
69 Xia Y, Farquhar T, Burton-Wurster N, Lust G. Origin of cartilage laminae in MRI. J Magn Reson Imag . 1997; 7 887-894
70 Hayes C W, Parellada J A. The magic angle effect in musculoskeletal MR imaging. Top Magn Reson Imag . 1996; 8 51-56
71 Rubenstein J, Recht M, Disler D G, Kim J, Henkelman R M. Laminar structures on MR images of articular cartilage. Radiology . 1997; 204 15-18
72 Cova M, Toffanin R, Frezza F. Magnetic resonance imaging of articular cartilage: ex vivo study on normal cartilage correlated with magnetic resonance microscopy. Eur Radiol . 1998; 8 1130-1136
73 Xia Y. Heterogeneity of cartilage laminae in MR imaging. J Magn Reson Imag. 2000b; 11 686-693
74 Goodwin D W, Zhu H, Dunn J F. In vitro MR imaging of hyaline cartilage: correlation with scanning electron microscopy. Am J Roentgenol . 2000; 174 405-409
75 Weiss C, Rosenberg L, Helfet A J. An ultrastructural study of normal young adult human articular cartilage. J Bone Joint Surg Am . 1968; 50 663-674
76 Hacker S A, Healey R M, Yoshioka M, Coutts R D. A methodology for the quantitative assessment of articular cartilage histomorphometry. Osteoarth Cartil . 1997; 5 343-355
77 Mosher T J, Smith H, Dardzinski B J, Schmithorst V J, Smith M B. MR imaging and t2 mapping of femoral cartilage: in vivo determination of the magic angle effect. Am J Roentgenol . 2001; 177 665-669
78 Maroudas A. Physicochemical properties of cartilage in the light of ion exchange theory. Biophys J . 1968; 8 575-595
79 Maroudas A, Muir H, Wingham J. The correlation of fixed negative charge with glycosaminoglycan content of human articular cartilage. Biochim Biophys Acta . 1969; 177 492-500
80 Maroudas A. Distribution and diffusion of solutes in articular cartilage. Biophys J . 1970; 10 365-379
81 Maroudas A, Thomas H. A simple physicochemical micromethod for determining fixed anionic groups in connective tissue. Biochim Biophys Acta . 1970; 215 214-216
82 Maroudas A. A study of ionic equilibria in cartilage. Connect Tiss Res . 1972; 1 69-77
83 Maroudas A. Physicochemical properties of articular cartilage. In: Adult Articular Cartilage London: Pitman 1979: 215-290
84 Maroudas A, Weinberg P D, Parker K H, Winlove C P. The distributions and diffusivities of small ions in chondroitin sulphate, hyaluronate and some proteoglycan solutions. Biophys Chem . 1988; 32 257-270
85 Donahue K M, Burstein D, Manning W J, Gray M L. Studies of Gd-DTPA relaxivity and proton exchange rates in tissue. Magn Reson Med . 1994; 32 66-76
86 Shane O RS, Williams S NO, Obradovic B, Burstein D. MRI measurements of fixed charge density as a measure of glycosaminoglycan content and distribution in tissue engineered cartilage (Abstract). New Orleans: Orthopaedic Research Society, March 16-19 1998
87 Tiderius C, Olsson L, deVerdier H, Leander P, Ekberg O, Dahlberg L. Gadolinium enhanced MRI of knee joint cartilage in osteoarthritis, Orthopaedic Research Society. Orlando, FL: March 12-15 2000
88 Tiderius C J, Olsson L-E, Leander P, DeVerdier H, Dahlberg L. Gadolineum (Gd-DTPA2-) enhanced MRI can differentiate between arthroscopically healthy and degenerated human knee joint cartilage. Orthopaedic Research Society. Anaheim, CA: February 1-4 1999
89 Gillis A, Bashir A, McKeon B, Scheller A, Gray M L, Burstein D. MR Imaging of relative glycosaminoglycan distribution in patients with autologous chondrocyte transplants. Invest Radiol . 2001; 36(12) 743-748
90 Stanisz G J, Henkelman R M. Gd-DTPA relaxivity depends on macromolecular content. Magn Reson Med . 2000; 44 665-667
91 Gillis A, Gray M L, Burstein D. Relaxivity of gadolinium agents in cartilage at 2T: effects on dGEMRIC imaging, International Society of Magnetic Resonance in Medicine. Glasgow, Scotland: April 21-27 2001
92 Nieminen M T, Toyras J, Rieppo J. Quantitative MR microscopy of enzymatically degraded articular cartilage. Magn Reson Med . 2000; 43 676-681
93 Nieminen M T, Toyras J, Laasanen M S. MRI quantitation of proteoglycans predicts cartilage stiffness in bovine humeral head, Orthopaedic Research Society. San Francisco, CA: February 25-28 2001
94 Samosky J, Burstein D, Martin S, Grimson E, Gray M. Spatially-localized GAG mapping with dGEMRIC predicts the compressive load response of the articular cartilage surface to in situ indentation testing, Orthopaedic Research Society. Dallas, TX: February 10-13 2002