- Email: [email protected]
The relationship between MRI findings and the relative signal intensity of retrodiscal tissue in patients with temporomandibular joint disorders
The relationship between MRI findings and the relative signal intensity of retrodiscal tissue in patients with temporomandibular joint disorders Sang-Hwa Lee, DDS, PhD,a and Hyun-Joong Yoon, DDS, PhD,b Seoul, Republic of Korea THE CATHOLIC UNIVERSITY OF KOREA
Objective. The purpose of this study was to evaluate the relationship between magnetic resonance imaging (MRI) findings and the relative signal intensity (RSI) of retrodiscal tissue in patients with temporomandibular joint disorders (TMDs) and to determine the usefulness of RSI as a diagnostic marker. Study design. One hundred and thirty-two temporomandibular joints in 66 TMD patients were analyzed. The signal intensities of regions of interest (ROIs) in retrodiscal tissues were measured using T2-weighted MRI. The RSIs of retrodiscal tissues were referenced to the signal intensities of the ROIs of brain gray matter. The relationships between the RSI of retrodiscal tissue and condylar degenerative change (Wilcoxon rank sum test), joint effusion (Wilcoxon rank sum test), disc position (Kruskal-Wallis test), pain (Wilcoxon rank sum test), and limited mouth opening (Wilcoxon rank sum test) were determined. Results. A strong association was seen between retrodiscal-tissue RSI and disc displacement, joint effusion, condylar degenerative change, and joint pain. Limited mouth opening did not significantly correlate with retrodiscal-tissue RSI. Conclusion. The retrodiscal-tissue RSI for T2-weighted MRI is a valuable noninvasive tool for monitoring the progression of TMD. Additional clinical studies are warranted. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:113-115)
Temporomandibular joint disorder (TMD) not only affects disc and bone tissue, but also can induce inflammation and/or fibrotic adhesion in retrodiscal tissue, and this may affect the clinical symptoms of this disorder. Although magnetic resonance imaging (MRI) is a noninvasive procedure that demonstrates temporomandibular joint (TMJ) structures, there is little information on the relationship between the MRI findings of retrodiscal tissue and clinical symptoms. The purpose of this study was to evaluate the relationship between MRI findings and relative signal intensity (RSI) of retrodiscal tissue in patients with TMD and to determine the usefulness of RSI as a diagnostic marker. PATIENTS AND METHODS The study group consisted of 66 consecutive TMD patients (132 joints) that presented at the Department of Oral and Maxillofacial Surgery, St. Mary’s Hospital, a
Assistant Professor, Department of Oral and Maxillofacial Surgery, St. Mary’s Hospital, the Catholic University of Korea, Seoul, Republic of Korea. b Associate Professor and Director, Department of Oral and Maxillofacial Surgery, St. Mary’s Hospital, the Catholic University of Korea, Seoul, Republic of Korea. Received for publication Nov 14, 2007; returned for revision Feb 20, 2008; accepted for publication Feb 25, 2008. 1079-2104/$ - see front matter © 2009 Mosby, Inc. All rights reserved. doi:10.1016/j.tripleo.2008.02.027
the Catholic University of Korea, Republic of Korea, from May 2003 to December 2006. All patients exhibited more than one of the following TMD symptoms: joint pain, sounds associated with jaw movement, or limited mouth opening. The patients comprised 54 females and 12 males with a mean age of 29 years and an age range from 13 to 65 years. This study protocol was approved by institutional review board of St. Mary’s Hospital, The Catholic University of Korea. MRI was performed with a GE Signa Exite twin speed (GE Medical Systems, Madison, WI). The following parameters of imaging for obtaining T2weighted images were used in the sagittal planes at the closed mouth position: TR-2600, TE-88.6, section thickness of 3 mm and a 320 ⫻ 224 matrix with a field of view of 120 ⫻ 120 mm. Measurements of the signal intensities were made directly on the MR imager for the T2-weighted sagittal closed mouth images. Before starting the study, we tested different sizes of regions of interest (ROIs) to measure the T2 signal. We found a diameter of 0.27 mm was optimal for our study (data not shown). For each measurement, a 0.27-mm (in diameter) ROI was defined and placed over the retrodiscal tissue and in the gray matter of the brain (Fig. 1). This was the largest area that could be consistently used throughout the study without including volume averaging from structures outside of retrodiscal tissue. The ROI in retrodiscal tissue was located adjacent to the posterior border of the disc. The ROI in the gray matter 113
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Table I. Associations between the MRI findings and relative signal intensities (RSIs) of retrodiscal tissues
Fig. 1. A 0.27-mm (in diameter) region of interest was defined and placed over the retrodiscal tissue and in the gray matter of the brain (arrows).
of the brain was placed just above a portion of the skull base located at the 12 o’clock position relative to the center of the condylar head. The RSI of the retrodiscal tissue was referenced to the signal intensity of the ROI in the gray matter of the brain (RSI of retrodiscal tissue ⫽ signal intensity of ROI in retrodiscal tissue/signal intensity of the ROI in the gray matter of the brain). The MRI studies were assessed in detail in a blinded fashion as to symptoms by one of the investigators using established criteria for normal disc position versus disc displacement. A normal disc position was defined as the posterior band of the disc being located at the superior or 12 o’clock position relative to the condyle. Primary categories of the joint status that were also assessed and tabulated were (1) a normal disc position, (2) anterior disc displacement with reduction, and (3) anterior disc displacement without reduction. Osteoarthrosis was defined by the presence of condylar deformities associated with flattening, subchondral sclerosis, surface irregularity, erosion, and osteophyte presence.1 The criteria of definition of a joint effusion has been previously reported.2 A T2-weighted MRI finding of no high signal or a line of signal along the articular surface was defined as negative, and when more than one line of high signal, such as spot intensity, was present inside the upper or lower joint compartment, it was regarded as joint effusion. The relationships between the RSI of retrodiscal tissue and osteoarthrosis (Wilcoxon rank sum test), joint effusion (Wilcoxon rank sum test), disc position (Kruskal-Wallis test), pain (Wilcoxon rank sum test), and limited mouth opening (Wilcoxon rank sum test) were determined. The TMJ was considered the unit of analysis—that is, each TMJ was considered an independent case.
Joint status Normal Abnormal Osteoarthrosis Normal Present Joint effusion Normal Present Disc position Normal ADWR ADOR
Number of joints
RSI (mean ⫾ SD)
P value
26 106
0.206 ⫾ 0.09 0.338 ⫾ 0.14
⬍.01
97 35
0.284 ⫾ 0.13 0.389 ⫾ 0.14
⬍.01
75 57
0.237 ⫾ 0.09 0.410 ⫾ 0.13
⬍.01
47 55 30
0.217 ⫾ 0.09 0.298 ⫾ 0.12 0.387 ⫾ 0.15
⬍.01
Joint status, osteoarthrosis, and joint effusion: (Wilcoxon rank sums, P ⬍ .01), disc position: (Kruskal-Wallis Test, P ⬍ .01). ADWR, anterior displacement with reduction; ADOR, anterior displacement without reduction.
RESULTS The average RSI of retrodiscal tissue was higher in the abnormal joints (joints that showed osteoarthrosis, joint effusion, or an abnormal disc position by MRI) than in the normal joints (P ⬍ .05). A statistically significant association between the RSI of retrodiscal tissue and the diagnosis of the joint with respect to osteoarthrosis, joint effusion, or disc position (P ⬍ .05, Table I) was seen. The average RSI of retrodiscal tissue was significantly higher in the joint with pain than in the joint without pain (P ⬍ .05) and was not associated significantly with the degree of mouth opening (P ⬍ .05, Table II). DISCUSSION MRI is a noninvasive procedure that demonstrates TMJ structures. Some of the specific MRI findings for the TMJ such as osteoarthrosis, joint effusion, and disc position have been studied to diagnose TMDs. Especially, a relationship between the MRI findings and clinical symptoms in TMD patients has been reported.3,4 Retrodiscal tissue (posterior disc attachment) of the TMJ has attracted extensive interest from both clinicians and researchers because of its possible role as a cause of TMD.5 Morphological changes in the shape and histological composition of retrodiscal tissue have been described in anatomic and surgical specimens and in a few in vivo reports with findings assessed by means of MRI. Histological studies have been performed with retrodiscal tissue removed from patients with painful disc displacement; these studies have demonstrated a
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Table II. Association between clinical symptoms and relative signal intensities (RSIs) of retrodiscal tissues Pain Normal Present Mouth opening Normal (⬎40 mm) Limited (⬍40mm)
Number of joints
RSI (mean ⫾ SD)
P value
77 55
0.284 ⫾ 0.13 0.349 ⫾ 0.15
.01
86 46
0.308 ⫾ 0.14 0.318 ⫾ 0.15
.79
(Wilcoxon rank sums, P ⬍ .05)
higher density of fibroblasts as compared with normal joints.6 MRI is useful for studying retrodiscal tissue noninvasively in that it allows in vivo characterization of the fine structural details of retrodiscal tissue and permits the separation of normal from the internally deranged temporomandibular joints.7 Decreased MRI signal intensity from retrodiscal tissue is most frequently associated with the later stages of disc displacement; however, its clinical significance remains unclear because there is no appreciable correlation to patient symptoms of pain.5 A possible association between pain and the T2 signal intensity from retrodiscal tissue was suggested in a study for which 4 ⫻ 4 mm areas of interest were placed over the retrodiscal tissues, with the cerebral cortex of the temporal lobe and the lower head of the lateral pterygoid muscle used as control areas. 8 In this study, the average T2 signal from retrodiscal tissue was higher in painful joints than in nonpainful joints, and this might reflect an increased vascularity of the joint tissue.8 In our study, we defined and standardized ROIs to obtain signal intensities. We did this by making measurements from the retrodiscal tissue as well as from the cerebral cortex of the temporal lobe. We made measurements of the temporal lobe to determine if there were any systematic signal differences between the different groups analyzed. RSI was calculated with the signal intensity of retrodiscal tissue and the gray matter. We evaluated the relationship between MRI findings and RSIs of retrodiscal tissues in patients with TMDs. The results demonstrated a statistically significant association between the RSIs of retrodiscal tissues and the diagnoses of joints with respect to osteoarthrosis, joint effusion, and disc position. The average RSI of retrodiscal tissue was significantly higher in the joint with pain than in a joint without pain. For our study of 66 consecutive TMD patients, we treated each of the 132 temporomandibular joints as an independent case. Although this is a violation of the
statistical assumption of independence, we think this is warranted for this preliminary investigation. In conclusion, in this study it was demonstrated that the RSI of retrodiscal tissue of the TMJ may provide a noninvasive method for the evaluation of TMD progression. Future signal-intensity analyses should be focused on retrodiscal-tissue evaluations and the factors that contribute to the signals. REFERENCES 1. Tasaki MM, Westesson PL. Temporomandibular joint: diagnostic accuracy with sagittal and coronal MR imaging. Radiology 1993;186:723-9. 2. Westesson PL, Brooks SL. Temporomandibular joint: relationship between MR evidence of effusion and the presence of pain and disk displacement. Am J Roentogenol 1992;159:559-63. 3. Murakami K, Nishida M, Bessho K, Iizuka T, Tsuda Y, Konishi J. MRI evidence of high signal intensity and temporomandibular arthralgia and relating pain. Does the high signal correlate to the pain? Br J Oral Maxillofac Surg 1996;34:220-4. 4. Manfredini D, Tognini F, Zampa V, Bosco M. Predictive value of clinical findings for temporomandibular joint effusion. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;96:521-6. 5. Westesson PL, Paesani D. MR imaging of the TMJ. Decreased signal from the retrodiskal tissue. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1993;76:631-5. 6. Kurita K, Westesson PL, Sternby NH. Histologic features of the temporomandibular joint disk and posterior disk attachment: comparison of symptom-free persons with normally positioned disks and patients with internal derangement. Oral Surg Oral Med Oral Pathol 1989;67:635-43. 7. Katzberg RW, Tallents RH. Normal and abnormal temporomandibular joint disc and posterior attachment as depicted by magnetic resonance imaging in symptomatic and asymptomatic subjects. J Oral Maxillofac Surg 2005;63:1155-61. 8. Sano T, Westesson PL. Magnetic resonance imaging of the temporomandibular joint. Increased T2 signal in the retrodiskal tissue of painful joints. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79:511-6. Reprint requests: Hyun-Joong Yoon, DDS, PhD Department of Oral and Maxillofacial Surgery St. Mary’s Hospital, the Catholic University of Korea #62 Youido-dong, Yeongdeungpo-gu Seoul, 150-713, Republic of Korea [email protected]
Objective. The purpose of this study was to evaluate the relationship between magnetic resonance imaging (MRI) findings and the relative signal intensity (RSI) of retrodiscal tissue in patients with temporomandibular joint disorders (TMDs) and to determine the usefulness of RSI as a diagnostic marker. Study design. One hundred and thirty-two temporomandibular joints in 66 TMD patients were analyzed. The signal intensities of regions of interest (ROIs) in retrodiscal tissues were measured using T2-weighted MRI. The RSIs of retrodiscal tissues were referenced to the signal intensities of the ROIs of brain gray matter. The relationships between the RSI of retrodiscal tissue and condylar degenerative change (Wilcoxon rank sum test), joint effusion (Wilcoxon rank sum test), disc position (Kruskal-Wallis test), pain (Wilcoxon rank sum test), and limited mouth opening (Wilcoxon rank sum test) were determined. Results. A strong association was seen between retrodiscal-tissue RSI and disc displacement, joint effusion, condylar degenerative change, and joint pain. Limited mouth opening did not significantly correlate with retrodiscal-tissue RSI. Conclusion. The retrodiscal-tissue RSI for T2-weighted MRI is a valuable noninvasive tool for monitoring the progression of TMD. Additional clinical studies are warranted. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:113-115)
Temporomandibular joint disorder (TMD) not only affects disc and bone tissue, but also can induce inflammation and/or fibrotic adhesion in retrodiscal tissue, and this may affect the clinical symptoms of this disorder. Although magnetic resonance imaging (MRI) is a noninvasive procedure that demonstrates temporomandibular joint (TMJ) structures, there is little information on the relationship between the MRI findings of retrodiscal tissue and clinical symptoms. The purpose of this study was to evaluate the relationship between MRI findings and relative signal intensity (RSI) of retrodiscal tissue in patients with TMD and to determine the usefulness of RSI as a diagnostic marker. PATIENTS AND METHODS The study group consisted of 66 consecutive TMD patients (132 joints) that presented at the Department of Oral and Maxillofacial Surgery, St. Mary’s Hospital, a
Assistant Professor, Department of Oral and Maxillofacial Surgery, St. Mary’s Hospital, the Catholic University of Korea, Seoul, Republic of Korea. b Associate Professor and Director, Department of Oral and Maxillofacial Surgery, St. Mary’s Hospital, the Catholic University of Korea, Seoul, Republic of Korea. Received for publication Nov 14, 2007; returned for revision Feb 20, 2008; accepted for publication Feb 25, 2008. 1079-2104/$ - see front matter © 2009 Mosby, Inc. All rights reserved. doi:10.1016/j.tripleo.2008.02.027
the Catholic University of Korea, Republic of Korea, from May 2003 to December 2006. All patients exhibited more than one of the following TMD symptoms: joint pain, sounds associated with jaw movement, or limited mouth opening. The patients comprised 54 females and 12 males with a mean age of 29 years and an age range from 13 to 65 years. This study protocol was approved by institutional review board of St. Mary’s Hospital, The Catholic University of Korea. MRI was performed with a GE Signa Exite twin speed (GE Medical Systems, Madison, WI). The following parameters of imaging for obtaining T2weighted images were used in the sagittal planes at the closed mouth position: TR-2600, TE-88.6, section thickness of 3 mm and a 320 ⫻ 224 matrix with a field of view of 120 ⫻ 120 mm. Measurements of the signal intensities were made directly on the MR imager for the T2-weighted sagittal closed mouth images. Before starting the study, we tested different sizes of regions of interest (ROIs) to measure the T2 signal. We found a diameter of 0.27 mm was optimal for our study (data not shown). For each measurement, a 0.27-mm (in diameter) ROI was defined and placed over the retrodiscal tissue and in the gray matter of the brain (Fig. 1). This was the largest area that could be consistently used throughout the study without including volume averaging from structures outside of retrodiscal tissue. The ROI in retrodiscal tissue was located adjacent to the posterior border of the disc. The ROI in the gray matter 113
114
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Table I. Associations between the MRI findings and relative signal intensities (RSIs) of retrodiscal tissues
Fig. 1. A 0.27-mm (in diameter) region of interest was defined and placed over the retrodiscal tissue and in the gray matter of the brain (arrows).
of the brain was placed just above a portion of the skull base located at the 12 o’clock position relative to the center of the condylar head. The RSI of the retrodiscal tissue was referenced to the signal intensity of the ROI in the gray matter of the brain (RSI of retrodiscal tissue ⫽ signal intensity of ROI in retrodiscal tissue/signal intensity of the ROI in the gray matter of the brain). The MRI studies were assessed in detail in a blinded fashion as to symptoms by one of the investigators using established criteria for normal disc position versus disc displacement. A normal disc position was defined as the posterior band of the disc being located at the superior or 12 o’clock position relative to the condyle. Primary categories of the joint status that were also assessed and tabulated were (1) a normal disc position, (2) anterior disc displacement with reduction, and (3) anterior disc displacement without reduction. Osteoarthrosis was defined by the presence of condylar deformities associated with flattening, subchondral sclerosis, surface irregularity, erosion, and osteophyte presence.1 The criteria of definition of a joint effusion has been previously reported.2 A T2-weighted MRI finding of no high signal or a line of signal along the articular surface was defined as negative, and when more than one line of high signal, such as spot intensity, was present inside the upper or lower joint compartment, it was regarded as joint effusion. The relationships between the RSI of retrodiscal tissue and osteoarthrosis (Wilcoxon rank sum test), joint effusion (Wilcoxon rank sum test), disc position (Kruskal-Wallis test), pain (Wilcoxon rank sum test), and limited mouth opening (Wilcoxon rank sum test) were determined. The TMJ was considered the unit of analysis—that is, each TMJ was considered an independent case.
Joint status Normal Abnormal Osteoarthrosis Normal Present Joint effusion Normal Present Disc position Normal ADWR ADOR
Number of joints
RSI (mean ⫾ SD)
P value
26 106
0.206 ⫾ 0.09 0.338 ⫾ 0.14
⬍.01
97 35
0.284 ⫾ 0.13 0.389 ⫾ 0.14
⬍.01
75 57
0.237 ⫾ 0.09 0.410 ⫾ 0.13
⬍.01
47 55 30
0.217 ⫾ 0.09 0.298 ⫾ 0.12 0.387 ⫾ 0.15
⬍.01
Joint status, osteoarthrosis, and joint effusion: (Wilcoxon rank sums, P ⬍ .01), disc position: (Kruskal-Wallis Test, P ⬍ .01). ADWR, anterior displacement with reduction; ADOR, anterior displacement without reduction.
RESULTS The average RSI of retrodiscal tissue was higher in the abnormal joints (joints that showed osteoarthrosis, joint effusion, or an abnormal disc position by MRI) than in the normal joints (P ⬍ .05). A statistically significant association between the RSI of retrodiscal tissue and the diagnosis of the joint with respect to osteoarthrosis, joint effusion, or disc position (P ⬍ .05, Table I) was seen. The average RSI of retrodiscal tissue was significantly higher in the joint with pain than in the joint without pain (P ⬍ .05) and was not associated significantly with the degree of mouth opening (P ⬍ .05, Table II). DISCUSSION MRI is a noninvasive procedure that demonstrates TMJ structures. Some of the specific MRI findings for the TMJ such as osteoarthrosis, joint effusion, and disc position have been studied to diagnose TMDs. Especially, a relationship between the MRI findings and clinical symptoms in TMD patients has been reported.3,4 Retrodiscal tissue (posterior disc attachment) of the TMJ has attracted extensive interest from both clinicians and researchers because of its possible role as a cause of TMD.5 Morphological changes in the shape and histological composition of retrodiscal tissue have been described in anatomic and surgical specimens and in a few in vivo reports with findings assessed by means of MRI. Histological studies have been performed with retrodiscal tissue removed from patients with painful disc displacement; these studies have demonstrated a
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Table II. Association between clinical symptoms and relative signal intensities (RSIs) of retrodiscal tissues Pain Normal Present Mouth opening Normal (⬎40 mm) Limited (⬍40mm)
Number of joints
RSI (mean ⫾ SD)
P value
77 55
0.284 ⫾ 0.13 0.349 ⫾ 0.15
.01
86 46
0.308 ⫾ 0.14 0.318 ⫾ 0.15
.79
(Wilcoxon rank sums, P ⬍ .05)
higher density of fibroblasts as compared with normal joints.6 MRI is useful for studying retrodiscal tissue noninvasively in that it allows in vivo characterization of the fine structural details of retrodiscal tissue and permits the separation of normal from the internally deranged temporomandibular joints.7 Decreased MRI signal intensity from retrodiscal tissue is most frequently associated with the later stages of disc displacement; however, its clinical significance remains unclear because there is no appreciable correlation to patient symptoms of pain.5 A possible association between pain and the T2 signal intensity from retrodiscal tissue was suggested in a study for which 4 ⫻ 4 mm areas of interest were placed over the retrodiscal tissues, with the cerebral cortex of the temporal lobe and the lower head of the lateral pterygoid muscle used as control areas. 8 In this study, the average T2 signal from retrodiscal tissue was higher in painful joints than in nonpainful joints, and this might reflect an increased vascularity of the joint tissue.8 In our study, we defined and standardized ROIs to obtain signal intensities. We did this by making measurements from the retrodiscal tissue as well as from the cerebral cortex of the temporal lobe. We made measurements of the temporal lobe to determine if there were any systematic signal differences between the different groups analyzed. RSI was calculated with the signal intensity of retrodiscal tissue and the gray matter. We evaluated the relationship between MRI findings and RSIs of retrodiscal tissues in patients with TMDs. The results demonstrated a statistically significant association between the RSIs of retrodiscal tissues and the diagnoses of joints with respect to osteoarthrosis, joint effusion, and disc position. The average RSI of retrodiscal tissue was significantly higher in the joint with pain than in a joint without pain. For our study of 66 consecutive TMD patients, we treated each of the 132 temporomandibular joints as an independent case. Although this is a violation of the
statistical assumption of independence, we think this is warranted for this preliminary investigation. In conclusion, in this study it was demonstrated that the RSI of retrodiscal tissue of the TMJ may provide a noninvasive method for the evaluation of TMD progression. Future signal-intensity analyses should be focused on retrodiscal-tissue evaluations and the factors that contribute to the signals. REFERENCES 1. Tasaki MM, Westesson PL. Temporomandibular joint: diagnostic accuracy with sagittal and coronal MR imaging. Radiology 1993;186:723-9. 2. Westesson PL, Brooks SL. Temporomandibular joint: relationship between MR evidence of effusion and the presence of pain and disk displacement. Am J Roentogenol 1992;159:559-63. 3. Murakami K, Nishida M, Bessho K, Iizuka T, Tsuda Y, Konishi J. MRI evidence of high signal intensity and temporomandibular arthralgia and relating pain. Does the high signal correlate to the pain? Br J Oral Maxillofac Surg 1996;34:220-4. 4. Manfredini D, Tognini F, Zampa V, Bosco M. Predictive value of clinical findings for temporomandibular joint effusion. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;96:521-6. 5. Westesson PL, Paesani D. MR imaging of the TMJ. Decreased signal from the retrodiskal tissue. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1993;76:631-5. 6. Kurita K, Westesson PL, Sternby NH. Histologic features of the temporomandibular joint disk and posterior disk attachment: comparison of symptom-free persons with normally positioned disks and patients with internal derangement. Oral Surg Oral Med Oral Pathol 1989;67:635-43. 7. Katzberg RW, Tallents RH. Normal and abnormal temporomandibular joint disc and posterior attachment as depicted by magnetic resonance imaging in symptomatic and asymptomatic subjects. J Oral Maxillofac Surg 2005;63:1155-61. 8. Sano T, Westesson PL. Magnetic resonance imaging of the temporomandibular joint. Increased T2 signal in the retrodiskal tissue of painful joints. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79:511-6. Reprint requests: Hyun-Joong Yoon, DDS, PhD Department of Oral and Maxillofacial Surgery St. Mary’s Hospital, the Catholic University of Korea #62 Youido-dong, Yeongdeungpo-gu Seoul, 150-713, Republic of Korea [email protected]