these discussions with respect to novel MRI pulse sequences for evaluating ... Key words: Cartilage, MRI, Rapid imaging, dGEMRIC, Sodium, Osteoarthritis.
OsteoArthritis and Cartilage (2006) 14, A76eA86 ª 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.joca.2006.03.010
International Cartilage Repair Society
MRI of articular cartilage in OA: novel pulse sequences and compositional/functional markers Garry E. Goldy*, Deborah Bursteinz, Bernard Dardzinskix, Phillip Langk, Fernando Boada{ and Timothy Mosher# y Stanford University, USA z Massachusetts Institute of Technology, USA x University of Cincinnati, Cincinnati Children’s Hospital Medical Center, USA k Brigham and Women’s Hospital, USA { University of Pittsburgh, USA # Pennsylvania State University, USA Summary Osteoarthritis (OA) is a leading cause of disability worldwide. Magnetic resonance imaging (MRI), with its unique ability to image and characterize soft tissue non-invasively, has proven valuable in assessing cartilage in OA. The development of new, fast imaging methods with high contrast show promise to improve the magnetic resonance (MR) evaluation of this disease. In addition to morphologic MRI methods, MRI contrast mechanisms under development may reveal detailed information about the physiology of cartilage. It is anticipated that these and other MRI techniques will play an increasingly important role in assessing the success or failure of therapies for OA. On December 5 and 6, 2002, OMERACT (Outcome Measures in Rheumatology Clinical Trials) and OARSI (Osteoarthritis Research Society International) held a workshop in Bethesda, MD aiming at providing a state-of-the-art review of imaging outcome measures for OA of the knee to help guide scientists and pharmaceutical companies in the use of MRI in multi-site studies of OA. Applications of MRI were initially reviewed by a multidisciplinary, international panel of expert scientists and physicians from academia, the pharmaceutical industry and regulatory agencies. The findings of the panel were then presented to a wider group of participants for open discussion. The following report summarizes the results of these discussions with respect to novel MRI pulse sequences for evaluating articular cartilage of the knee in OA and notes any additional advances that have been made since. ª 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Key words: Cartilage, MRI, Rapid imaging, dGEMRIC, Sodium, Osteoarthritis.
MRI, with its excellent soft tissue contrast, is the best technique available for assessment of articular cartilage11e15. Imaging of regions of cartilage damage has the potential to provide morphologic information about the region, such as fissuring, and presence of partial or full thickness cartilage defects. The many tissue parameters that can be measured by MRI techniques have the potential to provide biochemical and physiological information about the repair or transplant as well. An ideal MRI study for cartilage should provide accurate assessment of cartilage thickness and volume, demonstrate morphologic changes of the cartilage surface, demonstrate internal cartilage signal changes, and allow evaluation of the subchondral bone for signal abnormalities. Also desirable would be an evaluation of the underlying cartilage physiology, including the status of the proteoglycan and collagen matrices. Unfortunately, conventional MRI sequences are limited in providing a detailed assessment of cartilage, lacking either spatial resolution16, or information about cartilage physiology.
Introduction Osteoarthritis (OA) is an important cause of disability in our society, affecting millions and resulting in loss of time at work and activity limitations1e5. OA is primarily a disease of articular cartilage, either from injury or from degeneration6e8. Magnetic resonance imaging (MRI) offers a non-invasive means of assessing the degree of damage to cartilage and adjacent bone, and effectiveness of treatment. Many imaging methods are available to assess articular cartilage. Conventional radiography can be used to detect gross loss of cartilage evident as narrowing of the distance between the bony components of the joint9, but it does not image cartilage directly. Secondary changes such as osteophyte formation can be seen, but conventional radiography is insensitive to early chondral damage. Arthrography, alone or combined with conventional radiography, Computed Tomography (CT) scanning, or MRI, is also mildly invasive and provides information limited to the contour of the cartilage surface10. *Address correspondence and reprint requests to: Garry E. Gold, M.D., 300 Pasteur Drive S0-68B, Stanford, CA 94305-9510, USA. Tel: 1-650-725-0130; Fax: 1-650-723-7296; E-mail: gold@ stanford.edu Received 17 March 2006; revision accepted 17 March 2006.
Conventional MRI methods One of the major advantages of MRI is the ability to manipulate contrast to highlight tissue types. The common A76
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Osteoarthritis and Cartilage Vol. 14, Supplement A contrast mechanisms used in MRI are two-dimensional or multi-slice T1-weighted, proton-density (PD), and T2weighted imaging. The appearance of these has changed over time with the introduction of fast or turbo spin-echo imaging and the use of fat saturation and water excitation. While the tissue relaxation times and imaging parameters are the major determinants of contrast between cartilage and fluid, lipid suppression increases contrast between non-lipid and lipid-containing tissues and affects how the magnetic resonance (MR) scanner sets the overall dynamic range of the image. The most common type of lipid suppression includes fat saturation, in which fat spins are excited then dephase prior to imaging. Another option is spectralespatial excitation, in which only water spins in a slice are excited17. Finally, in areas of magnetic field inhomogeneity, inversion recovery provides a way to suppress lipids at the expense of signal-to-noise. The type of contrast used in cartilage imaging is critical to the visibility of lesions and the signal-to-noise of the cartilage itself. While T2-weighted imaging creates contrast between cartilage and synovial fluid, it does so at the expense of cartilage signal. These scans are also often two-dimensional in nature, leaving a small gap between slices. Three-dimensional spoiled gradient recalled echo imaging with fat suppression (3D-SPGR) produces high cartilage signal, but low signal from adjacent joint fluid. Currently, this technique is the standard for morphologic imaging of cartilage14,18,19. MRI of OA requires close attention to the spatial resolution used. In order to see degenerative cartilage, imaging with resolution on the order of 0.2e0.4 mm is required16. The ultimate resolution achievable is governed by the signal-to-noise ratio (SNR) possible within a given imaging time and with a given radiofrequency coil. Ultimately, a high-resolution imaging technique that combines morphologic and physiologic information would be ideal in the evaluation of OA. Given current techniques, however, it is likely a combination of high-resolution morphologic imaging and some form of matrix evaluation will be most useful.
accuracy for cartilage lesions has been shown with 3DSPGR imaging20e22. There are two main disadvantages to this approach: lack of reliable contrast between cartilage and fluid that outlines surface defects, and long imaging times (about 8 min). In addition, SPGR uses spoiling at the end of each repetition time (TR) to reduce artifacts and achieve near T1-weighting. This reduces the overall signal compared with steady-state techniques. Faster morphologic imaging techniques are desirable for several reasons. First, shorter scan times equate to less patient motion and more accurate measurements. Patient discomfort and compliance are improved, which can be important in longitudinal studies. Second, a shorter overall scan can be improved in terms of spatial resolution while the SNR in the images can be brought back through averaging. Finally, less time spent on imaging morphology may allow for longitudinal studies looking at cartilage physiology and biochemistry. DEFT IMAGING
Driven equilibrium Fourier transform (DEFT) has been used in the past as a method of signal enhancement in
Advanced morphologic imaging of articular cartilage SPGR IMAGING
Considerable work in OA has been devoted to screening patients with high-resolution 3D imaging techniques. High
Fig. 1. Axial Driven Equilibrium Fourier Transform (DEFT) image of the patellofemoral joint of a normal volunteer. The contrast in DEFT enhances signal in synovial fluid while preserving cartilage signal. Excellent cartilage detail is seen. Reproduced with permission from Gold et al.46.
Fig. 2. Two sagittal images from the knee of a normal volunteer. (A) FEMR, scan time 2:43. (B) SPGR, scan time 8:56. Both scans were done at the same spatial resolution (512 256, 2 mm slice thickness), and have similar SNR. The higher SNR efficiency of FEMR allows a similar morphologic scan to be acquired in a much shorter time. Reproduced with permission from Gold et al.31.
A78 spectroscopy23. The sequence uses a 90( pulse to return magnetization to the z-axis, resulting in enhanced signal from tissue with long T1 relaxation times such as synovial fluid. Unlike conventional T1- or T2-weighted MRI, the contrast in DEFT is dependent on the ratio of T1/T2 of a given tissue. For cartilage imaging, DEFT produces contrast by enhancing the signal from synovial fluid rather than attenuation of cartilage signal as in T2-weighted sequences. This results in bright synovial fluid at short TR. At short TR, DEFT shows much greater cartilage to fluid contrast than SPGR, PD-FSE, or T2-weighted FSE24. A 3D MR technique that produces contrast while preserving cartilage signal would be ideal. DEFT imaging has been combined with a 3D echo-planar readout to make it an efficient 3D cartilage imaging technique. In DEFT there is no blurring of high spatial frequencies such as in proton-density FSE25. Unlike T2-weighted FSE, cartilage signal is preserved due to the short echo times (TE). A high-resolution 3D data set of the entire knee using 512 192 matrix, 14 cm field-of-view (FOV) and 3 mm slices can be acquired in about 6 min26,27. An example of a 3D-DEFT image in the patella is shown in Fig. 1.
BALANCED STEADY-STATE FREE PRECESSION IMAGING
Balanced steady-state free precession (BSSFP) MRI is an efficient, high signal method for obtaining 3D MR images28. This method has also been called True fast imaging with steady precession (FISP) imaging29. With recent advances in MR gradient hardware, it is now possible to use
G. E. Gold et al.: MRI of articular cartilage in OA BSSFP without suffering from the banding or off-resonance artifacts that have been a problem with this method. The best immunity to off-resonance artifacts using BSSFP is found when the TR is equal to the chemical shift between water and fat (2.2 ms at 1.5 T). Unfortunately, resolution adequate for cartilage imaging is not possible with such a short TR and current gradient hardware. Odd multiple cycles of this TR, such as 6.6 ms at 1.5 T, can be used with careful shimming. Fluctuating equilibrium magnetic resonance (FEMR) is a variant of BSSFP that may be useful in imaging cartilage in the knee30. FEMR may be useful for detecting cartilage defects in the knee. In scanning the entire knee, FEMR can produce 3D images with a 2 mm slice thickness, 512 256 matrix over a 16 cm FOV in about 2 min and 30 s31. An example of water images using high-resolution FEMR is shown in Fig. 2, compared with a 3D-SPGR image that took almost 9 min to acquire. The contrast produced in BSSFP sequences like FEMR is also favorable for cartilage imaging. Similar to DEFT, FEMR produces contrast based on the ratio of T1/T2 in tissues. This results in bright fluid signal while preserving cartilage signal. Other BSSFP approaches that may provide more reliable fat suppression at high resolution are to use linear combination BSSFP32, or fat-suppressed BSSFP. An example comparing FEMR, fat-suppressed BSSFP, linear combinations of BSSFP, and 3D-SPGR in a patient with knee pain is shown in Fig. 333. The largest disadvantage of FEMR and other BSSFPbased techniques is sensitivity to off-resonance artifacts. With modern shimming technology to improve field homogeneity, this is less of a problem. Another approach that is
Fig. 3. Axial images of the patella in a patient with knee pain. (A) Fast spin-echo image. (B) 3D fat-suppressed steady-state image. (C) Linear combinations of steady-state imaging. (D) FEMR image. Reproduced with permission from Hargreaves et al.33.
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Osteoarthritis and Cartilage Vol. 14, Supplement A relatively insensitive to field variations combines a fatewater separating technique known IDEAL (Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation) method with BSSFP34. An example of knee images using this technique is shown in Fig. 4. Excellent separation of fat and water are seen, with little off-resonance artifact. High-field MRI may enable the acquisition of morphologic images at resolution that cannot be achieved in a reasonable scan time at 1.5 T. Currently, 3.0 T scanners are becoming available that theoretically have twice the SNR of 1.5 T scanners. IDEAL fatewater separation is also available at 3.0 T35e38. An example of this is shown in Fig. 5. IDEAL SPGR and IDEAL gradient echo (GRE) techniques both produce excellent quality images with high resolution (0.3 0.6 1.5 mm). The SPGR method suppresses signal from joint fluid, while the GRE method accentuates it. These methods are less SNR efficient than BSSFP, but also less sensitive to field inhomogeneity. Also available are fat, water, and combined images that are corrected for chemical
Fig. 5. IDEAL imaging of cartilage at 3.0 T. Water images are shown, but fat and combined images are reconstructed with this method. (A) IDEAL SPGR. (B) IDEAL GRE with bright synovial fluid. Resolution in these images is 0.3 0.6 1.5 mm.
shift. This method could be used to measure subchondral bone thickness. The combination of advanced BSSFP-based imaging techniques and advanced fatewater separation techniques with high-field MRI shows promise to reduce scan times for morphologic imaging at the current resolutions used to create cartilage thickness maps and volume measurements. Alternatively, we can use a similar scan time to that done now on a 1.5 T system with 3D-SPGR and improve the resolution of the images, yielding greater accuracy of the measurements. The combination of the advanced morphologic imaging techniques with cartilage physiology and matrix measurements will be a powerful tool to evaluate OA.
Physiologic MRI of articular cartilage Fig. 4. Steady-state images of the knee of a normal volunteer acquired using an IDEAL technique for fat-water separation. (A) Water image. (B) Fat image. Note that joint fluid is bright in (A) using this BSSFP technique. Reproduced with permission from Gold et al.31.
ARTICULAR CARTILAGE COMPOSITION
Articular cartilage is approximately 70% water by weight. The remainder of the tissue consists predominately of type II collagen fibers and proteoglycans. The proteoglycans
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Fig. 6. Axial T2 map of the patella of a normal volunteer. Normal T2 relaxation times range from 20 to 70 ms, with the higher values closer to the superficial layers of the cartilage. High T2 relaxation times indicate disruption of the collagen network.
contain negative charges, therefore, mobile ions such as sodium (Naþ) or the MRI charged contrast agent Gd (DTPA)2 will distribute in cartilage in relation to the proteoglycan concentration. The collagen fibers have an ordered structure, making the water associated with them exhibit both magnetization transfer and magic-angle effects. Physiologic MRI of articular cartilage takes advantage of these characteristics to explore whether the collagen and proteoglycan matrices are intact.
measurements have also been shown to be anisotropic with respect to orientation in the main magnetic field44e46. Focal increases in T2 relaxation times within cartilage have been associated with matrix damage, particularly loss of collagen integrity42. Fig. 7 shows an example of this T2 mapping technique in a patient with cartilage damage and arthroscopic confirmation.
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T2 RELAXATION TIME MAPPING
MRI is characterized by excitation of water molecules and relaxation of the molecules back to an equilibrium state. The exponential time constants describing this relaxation are referred to as T1 and T2 relaxation times, and are constant for a given tissue at a given MR field strength. Changes in these relaxation times can be due to tissue pathology or introduction of a contrast agent. The T2 relaxation time of articular cartilage is a function of the water content, and collagen ultra structure of the tissue. Measurement of the spatial distribution of the T2 relaxation time may reveal areas of increased or decreased water content, correlating with cartilage damage. In order to measure the T2 relaxation time with a high degree of accuracy, attention must be taken with the MR technique39. Typically, a multi-echo spin-echo technique is used and signal levels are fitted to one or more decaying exponentials, depending upon whether it is felt that there is more than one distribution of T2 within the sample40. However, for TE used in conventional MRI a single exponential fit is adequate. An image of the T2 relaxation time is then generated with either a color or a grayscale map representing the relaxation time. Several investigators have measured the spatial distribution of T2 relaxation times within articular cartilage41,42. Fig. 6 shows the color-coded normal distribution of articular cartilage T2 relaxation times in the patella. Aging appears to be associated with a symptomatic increase in T2 relaxation times in the transitional zone43. Relaxation time
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Fig. 7. (A) Axial MRI with corresponding arthroscopy in a patient with cartilage damage. (B) Corresponding color-coded T2 map in the patella of the same patient.
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Normalized Distance Fig. 8. Intra-subject Z-score mapping of T2 relaxation time maps in articular cartilage. (A) Color-coded T2 map in patellar cartilage with increased focal T2 relaxation time in the median ridge at the subchondral bone interface. (B) Corresponding region-of-interest (ROI) and sample locations of four computer-generated profiles across the patellar cartilage. (C) Average T2 relaxation time plot (n ¼ 40 profiles) across the patellar cartilage, from subchondral bone (normalized distance of 0 is the subchondral bone, 1 is the articular surface). (D) Intra-subject Zscore map with a voxel cluster size of 4 and color-coded T2 relaxation time values 2 standard deviations from the average profile (P ¼ 0.018, Monte Carlo simulation). (E) Intra-subject Z-score map with cluster size increased to 5 voxels, 2 standard deviations greater than the corresponding average T2 relaxation time (P ¼ 0.002, Monte Carlo simulation). These same techniques can be applied to create inter-subject Z-score maps for population comparison studies.
Statistical analysis of T2 relaxation time data for both intra- and inter-subject variability is important for clinical trials and for longitudinal studies in OA. An intra-subject comparison of T2 mapping in articular cartilage is depicted in Fig. 8. This technique essentially compares each computer-generated profile through the articular cartilage with the average T2 relaxation time profile. Pixels that are statistically different from the average T2 relaxation time profile are colorcoded based on cluster size and the user chosen standard deviation. This technique can also be applied to compare populations of T2 maps with the Z-score now representing the inter-subject variability with a reference group. DIFFUSION-WEIGHTED IMAGING (DWI)
Imaging the diffusion of water through articular cartilage is also possible with MRI. DWI of cartilage has been demonstrated in vitro to be sensitive to early cartilage degradation47,48. The apparent diffusion coefficient (ADC) decreases at long diffusion times, indicative of the water molecules being restricted by cartilage components. At the diffusion times typically used, this restriction is related to the collagen network in cartilage49. Diffusion measurements are accomplished through application of diffusion-sensitizing gradients. These gradients cause phase accrual in the spins of the tissue, which is then reversed and reduced to
zero if the spins are stationary. Water undergoing diffusion, however, accrues a random amount of phase and does not refocus, resulting in signal loss in tissue undergoing diffusion. The amount of diffusion weighting applied depends on the amplitude and timing of the diffusion-sensitizing gradients and is termed the b-value. A map of the amount of diffusion that has occurred is usually constructed from images with and without diffusion gradients applied, and this map is called the ADC map. The term apparent is used since the diffusion coefficient is not that of bulk water since tissue membranes restrict water protons. In vivo DWI of cartilage poses several challenges. The T2 relaxation time of cartilage varies from 10 to 50 ms so the TE must be short to maximize cartilage signal. Diffusionsensitizing gradients increase the TE and render the sequence sensitive to motion. Single-shot techniques have been used for DWI, but these suffer from relatively low SNR and spatial resolution. Multiple acquisitions improve the SNR and resolution, but motion correction is required for accurate reconstruction50. Articular cartilage measurements done in vivo in healthy volunteers show that ADC ranges from 1.5 to 2 103 mm2/s. These values compare well with reported results obtained on cartilage/bone plug specimens51. Fig. 9 shows in vivo DWI results on a normal volunteer using a navigated DWI technique based on BSSFP52.
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Fig. 9. 3D BSSFP DWI. The b-values correspond to the degree of diffusion weighting. Diffusion imaging gives a sense of translational water mobility within the articular cartilage. Reproduced with permission from Miller et al.52. SODIUM MRI
Atoms with an odd number of protons and/or neutrons possess a nuclear spin momentum, and therefore exhibit the MR phenomenon. 23Na is an example on a nucleus other than 1H that is useful in cartilage imaging. The Larmor frequency of 23Na is 11.262 MHz/T, compared with 1H at 42.575 MHz/T. This means at 1.5 T, the resonant frequency of 23Na is 16.9 MHz, whereas it is 63 MHz for 1H. The concentration of 23Na in normal human cartilage is about 320 mM, with T2 relaxation times between 2 and 10 ms53. The combination of lower resonant frequency, lower concentration, and shorter T2 relaxation times than 1H make in vivo imaging of 23Na challenging. Sodium imaging requires the use of special transmit and receive coils as well as relatively long imaging times to achieve adequate signal-to-noise. Sodium MRI has recently shown some promising results in the imaging of articular cartilage. This is based on the ability of sodium imaging to depict regions of proteoglycan depletion54. 23Na atoms are associated with the high fixed-charge density present in proteoglycan sulfate and carboxylate groups. Some spatial variation in 23Na concentration is present within normal cartilage53. Fig. 10 shows an example of a sodium image through the patellar cartilage of a healthy volunteer done with a twisted-projection technique at 3.0 T55. High sodium concentration is seen throughout the normal cartilage. In cartilage samples, sodium imaging has been shown to be sensitive to small changes in proteoglycan concentration56. This method shows promise to be sensitive to early decreases in proteoglycan concentration in OA. It is also possible to do triple-quantum-filtered imaging of sodium in cartilage, which may be even more sensitive to early changes57. CONTRAST ENHANCED IMAGING (dGEMRIC)
The proteoglycan component of cartilage has glycosaminoglycan (GAG) side chains with abundant negatively
charged carboxyl and sulfate groups. Therefore, if mobile ions are allowed time to distribute in cartilage, they will distribute in relation to the negative fixed-charge density of the cartilage, or effectively in relation to the GAG concentration. One of the most common MRI contrast agents, Magnevist (Berlex, NJ), or Gd(DTPA)2, has a negative charge. If Gd(DTPA)2 is allowed to penetrate into cartilage, it will distribute in higher concentration in areas of cartilage in which the GAG content is relatively low and will distribute in lower concentration in areas rich in GAG. Subsequent T1 imaging (which is reflective of Gd(DTPA)2 concentration) will therefore yield an image depicting GAG distribution. This technique is referred to as delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) (the ‘‘delay’’ referring to the time required to allow the Gd(DTPA)2 to penetrate the cartilage tissue). The dGEMRIC technique has been validated in both basic science and clinical studies as being a reflection of the GAG concentration of cartilage in that the dGEMRIC measurement corresponds to ‘‘gold standard’’ measures for GAG of biochemistry and histology49,58,59. Clinical studies have demonstrated that dGEMRIC images show ‘‘lesions’’ in cartilage which are not observable in the presence of the nonionic contrast agent ProHance (Bracco Diagnostics, NJ)60, further validating that the dGEMRIC image corresponds to the distribution of the charged GAG molecules. An example of a dGEMRIC image showing lower GAG in the medial tibial plateau is shown in Fig. 11. The dGEMRIC technique allows one to track the distribution of GAG across cartilage over time in culture with high resolution, thereby enabling long-term in vitro studies of the evolution of repair and of factors that might be involved. For example, using dGEMRIC, bovine cartilage plugs were monitored over time with the observation that chondrocytes were able to replenish GAG after trypsin depletion of GAG61 and following interleukin-1 (IL-1) treatment62. Several pilot clinical studies have also been initiated using dGEMRIC to demonstrate the level of repair in cartilage implants in vivo33,63,64.
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Fig. 11. dGEMRIC image demonstrates lower dGEMRIC index (GAG) in the medial tibial plateau (shown in red) relative to the other articular cartilage surfaces. The variation of GAG in morphologically intact cartilage may yield information relative to early cartilage degeneration and possible repair.
of dGEMRIC, these include the issue of the conditions under which Gd(DTPA)2 fully penetrates cartilage, assumptions inherent in the conversion of T1 to Gd(DTPA)2 concentration (and hence GAG concentration), tissue cellularity in young or tissue engineered samples (since the Gd(DTPA)2 does not enter cells, and thus cellular volume needs to be corrected for), and better T1 sequences which can cover the knee in a reasonable time frame. These practical issues need to be investigated further in conjunction with further bench and clinical studies. However, the biophysical basis of the technique, coupled with the validation studies and demonstration of sensitivity to physiologic and pathologic processes in vitro and in vivo, lends support to the premise that this is a potentially valuable approach in investigating cartilage health, disease, and repair. Fig. 10. Twisted-projection imaging sodium images of the knee of a healthy volunteer done at 3.0 T. (A) Single-quantum images. (B) Triple-quantum images. Sodium content in the patellofemoral cartilage is well seen in both cases.
In terms of clinical studies, a number of cross-sectional studies of a specified population have provided interesting observations. For example, a recent study reported that individuals who exercise on a regular basis have higher dGEMRIC indices (denoting higher GAG) than individuals who are sedentary65. In a finding that is consistent with previous ex vivo biochemical studies, the medial compartment, in comparison with the lateral compartment, has generally lower values for the dGEMRIC index66 possibly reflecting a response to the different mechanical environment for the different compartments. In a relatively large cross-sectional study of patients with hip dysplasia, measures of severity of dysplasia (the radiographically-determined lateral center edge angle) and of pain both correlated with the dGEMRIC index, but not with the standard radiological parameter of joint space narrowing67. In another study, lesions in patients with OA were more apparent with the dGEMRIC technique relative to standard MRI scans68. As in all measuring techniques, there are assumptions and possible errors underlying the technique. In the case
Discussion and conclusions MRI provides a powerful tool for the imaging and understanding of OA. Improvements have been made in morphologic imaging of cartilage, in terms of contrast, resolution, and acquisition time. This allows detailed maps of the cartilage surface to be developed, quantifying both thickness and volume. Much progress has been made in the understanding of cartilage physiology, and the ability to detect changes in proteoglycan content and collagen ultra structure. Improvements still need to be made, however. The fundamental trade-off between image resolution and SNR still limits our ability to image cartilage in vivo with high resolution in an efficient manner. Patient motion may ultimately limit the resolution achievable at 1.5 T, so higher field systems may be required. New techniques based of BSSFP may allow more time in longitudinal studies to explore important questions about cartilage physiology and biochemistry. Ideally, the combination of these techniques will lead to an MRI examination for OA that is brief and well tolerated but contains important morphologic and physiologic data. MRI is a powerful tool for evaluation of OA. New methods under development promise to further refine and enhance
A84 our ability to characterize both the morphology and biochemical content of cartilage lesions. Application of these methods in a clinical environment is challenging but holds promise to evaluate cartilage function as well. Overall, MRI is a flexible and important tool with which to study the evolution and progression of OA, evaluate new therapies, and provide new insight into the pathogenesis of this disease.
Recent updates Since the consensus meeting, there have been several important developments in cartilage imaging. In the area of morphologic imaging, advances have been made in DEFT imaging26,27, BSSFP imaging69,70, and in fatewater separation35. These sequences show promise to produce rapid and accurate information about cartilage morphology. Recent effort has also produced images of cartilage under physiologic loads in vivo71. In the area of physiologic cartilage imaging, several investigations have been published regarding the application of these techniques to different patient populations. Specifically, studies on T2 relaxation times documenting the effects of age72, gender73, and activity74 have been published. Recent publications also show the potential for diffusion imaging of cartilage52,75. Imaging with dGEMRIC has also been a very active area of research, with studies on early OA in hip dysplasia67, molecular and functional cartilage imaging76, and studies looking at the effects of gadolinium on measurement of T2 relaxation times77,78. A recent study relevant to OA showed that dGEMRIC correlated with Kellgren/Lawerence radiographic grading of OA79. Other studies have also shown dGEMRIC to be a promising method for monitoring GAG in patients with OA65,80. Continued interest in T1r imaging of articular cartilage has resulted in several studies on this method81e83. Sodium MRI continues to show promise for detection of GAG in cartilage as well84,85. Overall, advances continue to occur in morphologic and functional imaging of cartilage in OA, and these promise to improve our ability to study and understand this important disease.
Acknowledgments The authors would like to acknowledge the support of NIH grants AR46904, AR47179, AR47784, AR47363, EB002524, EB 005790, and AR-42773. We would also like to acknowledge the generous support of the Whitaker Foundation and Arthritis Foundation.
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