Magnetic resonance imaging in osteoporosis

EUROPEAN JOURNAL OF RADIOLOGY

ELSEVIER

European Journal of Radiology20 (1995) 193-197

Magnetic resonance imaging in osteoporosis * S h a r m i l a M a j u m d a r , H a r r y K. G e n a n t * Department of Radiology, University of California, San Francisco, CA 94143, USA

Received26 June 1995;accepted 30 June 1995

Keywords: Osteoporosis; Magnetic resonance (MR), osteoporosis

1. Introduction

Magnetic resonance (MR) is a complex technology which has evolved rapidly since its introduction to medical science in the early 1970s. Based upon application of high magnetic fields, transmission of radiofrequency (RF) waves and detection of RF signals from excited hydrogen protons, this technique has revolutionized medical imaging in general. MRI offers unique qualitative capabilities to non-invasively evaluate the musculoskeletal system, including assessment of compositional changes in the bone marrow and structural changes in osseous tissue. Recently, the capabilities of quantitative magnetic resonance (QMR) and magnetic resonance microscopy (MMR) have been explored for assessing osteoporosis in specific. Occult traumatic fractures or subtle atraumatic insufficiency fractures are common occurrences in the elderly osteoporotic population, and conventional radiographs are frequently unrevealing while radionuclide bone scanning shows improved sensitivity but poor specificity. Axial imaging with computed tomography provides improved specificity but only modest sensitivity for assessing occult fractures. MRI provides improved sensitivity and specificity compared to bone scintigraphy, particularly in the first several days following nondisplaced hip fractures when the latter may be negative * Presented at the symposium'Current Assessmentof Osteoporosis', Vienna, 5 March 1995. * Corresponding author.

[1,2]. MRI characteristically demonstrates irregular linear signal alteration at the fracture site, typically low signal on Tl-weighted images with adjacent high signal of normal fatty marrow, and high signal on T2-weighted images contrasted with low signal of adjacent marrow. These MR signal changes reflect the focal hyperemic and reparative processes, or in some cases condensation of trabeculae and callus formation. Of potentially equal importance and perhaps with wider clinical applications, MRI provides excellent capability for distinguishing acute from chronic or benign from malignant vertebral deformities or fractures [3-7]. Since a gold standard does not exist for defining fractures of the spine by qualitative or morphometric criteria, a method such as MRI, which exquisitely demonstrates not only the morphologic changes but also the underlying physio-chemical processes, may facilitate the clear distinction between true acute osteoporotic fractures and chronic vertebral deformities related to congenital or acquired processes. In this application, MRI combines the sensitivity of bone scintigraphy with the specificity of high resolution CT and surpasses both in overall accuracy of diagnosis. The altered marrow MR signal, associated with acute fractures, resolves in several months leaving only the residual deformed vertebra. Furthermore in the elderly, even radiographically apparent vertebral fractures may be either osteoporotic or neoplastic-induced, and MRI may enhance this important distinction [4,5]. While both neoplastic and reparative tissues have similar MR signal

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characteristics, vertebral fractures due to metastatic neoplasm typically show complete replacement of normal marrow signal of the deformed vertebra, often the vertebra showing anterior and posterior convex borders, while the adjacent non-fractured vertebrae frequently show discrete foci of altered signal representing additional neoplastic deposits. Benign osteoporotic fractures generally show marrow signal changes closely paralleling the fractured endplates with preservation of normal marrow signal in the non-deformed portions of the vertebrae. Adjacent non-fractured vertebrae in this setting show normal marrow signal. In the differentiation of acute traumatic versus acute osteoporotic vertebral fractures MRI may be limited because both show focally altered MR signal related to hemorrhage and repair. The degree of deformity and displacement of fragments may favor trauma, while the appearance of chronic deformities with normal marrow signal at other levels favors underlying osteoporosis. These qualitative applications of MRI are currently widely applied and are impacting on the clinical management of patients with osteoporosis. The methods of quantitative MR discussed below are largely research pursuits at this time. 2. Quantitative magnetic resonance To date, most MR imaging techniques have been limited to the study of soft tissue or of gross skeletal structure because the presence of compact bone in MR images results in a total absence of signal. However, newly developed quantitative magnetic resonance (QMR) techniques have been used to study trabecular bone, specifically. The presence of the trabecular bone matrix affects the signal intensity of bone marrow, an effect that is particularly enhanced in specific imaging sequences. The magnetic properties of trabecular bone and bone marrow are significantly different. These differences produce distortions of the magnetic lines of force, which make the local magnetic field within the tissue inhomogeneous and alter the relaxation properties of tissue, such as the apparent transverse relaxation time T2*, in gradient-echo images. From theoretical considerations, such changes in T2* should directly relate to the density of the surrounding trabecular network and its spatial geometry. The resultant shortening of relaxation time becomes greater with an increase in the concentration of trabecular bone in the surrounding homogeneous marrow tissue. Thus, in a normal dense trabecular network, T2* shortening should be more pronounced than in rarefied osteoporotic trabeculae. Experimental studies have confirmed the theoretical predictions, suggesting QMR as a promising tool for studying trabecular bone architecture and assessing osteoporosis. Davis et al. [8] have shown a reduction in the in vitro T2* of both water and cottonseed oil in the

presence of bone powder at a magnetic field strength of 5.9 Tesla (T). Rosenthal et al. [91 have measured a reduction in the T2* of water present in the trabecular spaces compared with extra-trabecular water, using specimens of excised human vertebrae at 0.6 T. Majumdar et al. [10] using specimens of dried human vertebral bodies with varying bone densities, have examined susceptibility mediated relaxation effects. The mean trabecular bone density for each specimen, measured by QCT, was significantly related to the overall relaxation rate l/T2* of intra-trabecular saline. Similar relations in vivo have also been established in the forearm, in the distal femur and proximal tibia sites at which the trabecular bone network shows significant variations as a function of the distance from the joint line, with the bone density and relaxation rate, l/T2*, being greatest in the epiphysis and progressively decreasing towards the metaphysis and diaphysis [11]. In studies on the distal radius, precision errors in measured T2* times were found to range from 1.3 to 2.9 ms, corresponding to 3.8 to 9.5% CV [12]. In a similar fashion, Wehrli et al. [13] have used a QMR method called MR interferometry to assess variations in T2* between osteoporotics and normals. Theoretically and from computer simulations [10,14] and phantom studies [ 151 the relaxtion time T2* of bone marrow is affected not only by the density of the trabecular matrix but also by its spatial architecture. In early experiments with specimens Majumdar et al. [16] have shown correlation between the elastic modulus which reflects the biomechanical properties of trabecular bone with T2*. Chung and Wehrli [17] found a strong correlation (r= 0.91) between the Young's modulus of elasticity and I/T2' in trabecular bone specimens from human lumbar spine, while Jergas et al. [181 have shown similar relationships using specimens of tibial bone. Thus, this measured QMR parameter T2* may enhance the capability for fracture discrimination and fracture risk prediction. This technique has the advantage that it can be performed at medium-to-low resolution, giving decreased acquisition times, and permitting the use of scanners at fields of 1.5 T or less. 3. Magnetic resonance microscopy MR microscopy (MMR) may be an additional MRbased technique to study trabecular microarchitecture in a quantitative manner both in vitro and in vivo. In vitro, using small RF surface coils in high-field scanners, MR microscopy can be performed at resolutions high enough to discriminate individual bone trabeculae [19,20]. In vitro images have been obtained at in plane resolutions as low as 33/~m, while in vivo images range from resolutions of 78 x 78 x 300 tzm through the phalanges [21] to images at a resolution of 156 x 156 x 700/~m in the distal radius [22] and 200 × 234 x 1000

S. Majudar, H.K. Genant/ European Journal of Radiology 20 (1995) 193-197

/~m in the calcaneus [23]. Typically, the image is first segmented into bone and marrow phases, and histomorphometric analysis is then performed on the resulting binary image. Stereological parameters such as the trabecular bone area and volume fraction, mean intercept length, mean trabecular width, mean trabecular spacing and trabecular number can thus be calculated. Wehrli et al. have compared the stereological measures of bone volume fraction derived from MR images obtained at 9.4 T and found good correlations [20], while Antich et al. have conducted similar experiments and found changes in accordance to histomorphometry measures [19]. Sarkar et al. have extended the in vitro techniques to obtain images in an overiectomized rat model and have shown the ability to measure changes in trabecular structure following overiectomy [24]. With the resolution achievable in vivo at clinical field strengths, due to limitations on the signal to noise and total imaging time, individual smaller trabeculae usually cannot be resolved, but the images rather show the larger trabeculae and the texture of the trabecular network. However, using standard techniques of stereology as well as texture analysis tools such as fractal analysis, the trabecular structure can be quantified. In an early study establishing the feasibility of using such images to quantify trabecular structure MR images of the distal radius have been obtained using a modified gradient echo sequence on a 1.5-T imager, at a spatial resolution of 156/~m, and slice thickness of 0.7 mm [22]. In Fig. 1. representative distal radius images in a normal and osteoporotic subject clearly depict the loss of trabecular bone and a sparse network in the osteoporotic subject.

a

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It is well known that the amount of trabecular bone is the greater at distal sites of the radius and decreases proximally and this is readily seen in the MR images. Similar images obtained in the calcaneus of a normal subject is shown in Fig. 2. The orientation of the trabeculae are significantly different in the sub-talar region compared to the posterior region for example. As seen in the figure the ellipse of the mean intercept length shows a preferred orientation and hence maps the anisotropy of trabecular structure. In preliminary in vivo studies in the calcaneus, gray-scale reference values from fat, muscle, and tendon were used to calculate a reproducible threshold value. This approach gave a long-term in vivo precision of - 3 - 5 % CV for trabecular width and spacing [25]. In MR the image appearance depends on several factors apart from image resolution. The sequence used to obtain the image, whether it is a spin-echo or gradient echo, the echo time, the magnetic field strength are all important factors that may modify the trabecular dimensions depicted in an MR image [26]. Furthermore, when the image resolution is comparable to the trabecular dimensions a small error is manifested as a large relative error, and hence the stereological measures from MR images are likely to be subject to these effects. In the image analysis of such images the threshold is also shown to have a significant effect on the estimated parameters [22]. However, despite these technical challenges by standardizing the image acquisition, analysis and by understanding the processes underlying image formation MR is a potential tool for assessing trabecular bone structure in vivo. It is a non-invasive,

b

Fig. i. High resolution magnetic resonance images of the distal radius in the axial plane. The image resolution is 156/~m in plane and 700/~m in slice thickness. The echo time is minimized to 8.4 ms and the total scan time is 19 rain. In these images the marrow is bright and the trabeculae appear as dark striations. (a) Osteoporotic subject, (b) Normal subject. Note the dense network in the normal subject and the parse trabecular network in the osteoporotic subject. [22]. In Fig. 1 representative distal radius images in a normal and osteoporotic subject cleanly depict the loss of trabecular bone and a sparse network in the osteoporotic subject.

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Fig. 2. High resolution magnetic resonance image through the sagittal plane in the calcaneus. The anisotropy of trabeculae (dark striations in bright marrow) are clearly seen. The mean intercept length, a measure of the mean trabecular width as a function of angle is shown in the figure. The major axis of the ellipse defines the preferred trabecular orientation. As is seen the anisotropy of trabeculae is most pronounced in the sub-talar region as is also demonstrated by the elliptical plot of the mean intercept length. The ellipses are scaled identically, thus from the figure it can also be seen that the thickest trabeculae are found in the sub-talar region.

non-ionizing technique and can provide three dimensional images in arbitrary orientations, and can depict trabecular structure. Although it is a relatively expensive technique to use for primary screening for osteoporosis it provides a potential platform for identifying particularly high risk patients after initial bone densitometry and perhaps assigning these patients tmore aggressive therapies. Furthermore, it provides a platform for in vivo monitoring of trabecular structural changes and understanding the pathophysiology of various disease processes and the action of various therapeutic regimes. References [1]

[2]

[3]

[4]

Rizzo PF, Gould ES, Lyden JP, Asnis SE. Diagnosis of occult fractures about the hip. Magnetic resonance imaging compared with bone-scanning. J Bone Joint Surg 1993; 75A: 395-401. Matin P. The appearance of bone scans following fractures, ineluding immediate and long term studies. J Nucl Med 1979: 20: 1227. Santoris D, Clopton P, Nemcek A, Dowd C, Resnick D. Vertebral-body collapse in focal and diffuse disease: patterns of pathologic processes. Radiology 1986; 160: 479-483. Yuh WT, Zachar CK, Barloon T J, Sato Y, Sickels W J, Hawes

DR. Vertebral compression fractures: distinction between benign and malignant causes with MR imaging. Radiology 1989; 172: 215-218. [5] Baker LL, Goodman SB, Perkash I, Lane B, Enzmann DR. Benign versus pathologic compression fractures of vertebral bodies: assessment with conventional spin-echo, chemical-shift, and STIR MR imaging. Radiology 1990; 174: 495-502. [6] Allgayer B vd, Flierdt yon GS, Heuck A, Matzner M, Lukas PI, Luttke G. NMR tomography compared to skeletal scintigraphy after traumatic vertebral body fractures. RoFo 1990; 152: 677-681. 17] Wiener SN, Neumann DR, Rzeszotarski MS. Comparison of magnetic resonance imaging and radionuclide bone imaging of vertebral fractures. Clin Nucl Med 1989; 14: 666-670. [8] Davis CA, Genant HK, Dunham JS. The effects of bone on proton NMR relaxation times of surrounding liquids. Invest Radiol 1986; 21: 472-477. [9] Rosenthal H, Thulborn KR, Rosenthal DI, Rosen BR. Magnetic susceptibility effects of trabecular bone on magnetic resonance bone marrow imaging. Invest Radiol 1990; 25: 173-178. [10] Majumdar S. Magnetic field inhomogeneity effects induced by inherent tissue susceptibility differences in gradient echo magnetic resonance imaging: computer simulations. Magn Reson Med 1991; 22: 101-110. [1 l l Majumdar S, G-enant H K. In vivo relationship between marrow T2* and trabecular bone density determined with a chemical shift-selective asymmetric spin-echo sequence. J Magn Reson Imaging 1992; 2: 209-219.

S. Majudar, H.K. Genant/ European Journal of Radiology 20 (1995) 193-197 [12] Grampp S, Majumdar S, Jergas M, Lang P, Gies A, Genant HK. MRI of bone marrow in the distal radius: in vivo precision of effective transverse relaxation times. Eur Radiol 1995; 5: 43-48. [13] Wehrli FW, Ford JC, Attic M, Kressel HY, Kaplan FS. Trabecular structure: preliminary application of MR interferometry. Radiology 1991; 179: 615-621. [14] Ford JC, Wehrli FW, Chung H. Magnetic Field Distribution in Models of Trabecular bone. Magn Reson Med 1993; 30: 373-379. [15] Engelke K, Majumdar S, Genant HK. Impact of trabecular structure on marrow relaxation time, T2*: phantom studies. Magn Reson Med 1994; 31: 380-387. [161 Majumdar S, Keyak J, Lee I, Genant HK, Skinner H. Relationship between marrow relaxation time T2* and elastic modulus. Berlin: Society of Magnetic Resonance in Medicine, 1992. [17] Chung H, Wehrli FW, Williams JL, Kugeimass SD. Relationship between NMR transverse relaxation, trabecular bone architecture, and strength. Proc Nati Acad Sci USA 1993; 90: 10250- !0254. [18] Jergas M, Majumdar S, Keyak JH, Lee IY, Newitt I)(2, Grampp S, Skinner HB, Genant HK. Relationships between Young's modulus of elasticity, ash density and magnetic resonance imaging (MRI) derived effective transverse relaxation time T2* in human tibial specimens. J Comput Assist Tomogr 1995. In press. [19] Antich P, Mason R, McColl R, Zerwech J, Pak C. Trabecular architecture studies by 3D MRI microscopy in bone biopsies. J Bone Miner Res 1994; 9-S1: 327.

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[20] Chung H, Wehrli F, Williams J, Kugelmass S, Wehrli S. Quantitative analysis of trabecular microstructure by 400 MHz Nuclear Magnetic Resonance Imaging. J Bone Miner Res 1995; 10:803-81 i.

[21] Jara H, Wehrli FW, Chung H, Ford JC. High-resolution variable flip angle 3D MR imaging of trabecular microstructure in vivo. Magn Reson Med 1993; 29: 528-539. [22] Majumdar S, Genant HK, Grampp S, Jergas M, Newitt D, Gies A. Analysis of trabecular bone structure in the distal radius using high resolution MRI. Eur Radiol 1994; 4: 517-524. [23] Majumdar S, Genant HK, Gies A, Guglielimi G. Regional variations in trabeeular structure in the caleaneus assessed using high resolution magnetic resonance images and quantitative image analysis. J Bone Miner Res 1993; 8S: 351. [241 Kapadia RD, High W, Bertolini D, Sarkar SK. MR microscopy: a novel diagnostic tool in osteoporosis research. 4th International Symposium on Osteoporosis and Consensus Development Conference, 1993: Hong Kong; 38. [251 Ouyang X, Lang P, Sclby K, Zucconi F, Gindele A, Klifa C, Engelke K, Majumdar S, Genant HK. Analysis of high resolution mri images of calcaneus: gray-level thresholding and trabeeular quantification. Society of Magnetic Resonance Third Scientific Meeting, 1995: Nice, France. [26] Majumdar S, Newitt 13(2,Jergas M, Gies AA, Chiu EC, Osman D, Keltner J, Keyak J, Genant HK. Evaluation of technical factors affecting the quantification of trabecular bone structure using magnetic resonance imaging. Bone 1995. In press.