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Published online before print December 21, 2005, 10.1148/radiol.2381041720

(Radiology 2005;238:650.)

A more recent version of this article appeared on December 1, 2005
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© RSNA, 2005

Musculoskeletal Imaging

Steroid Myopathy: Evaluation of Fiber Atrophy with T2 Relaxation Time—Rabbit and Human Study1

Masamitsu Hatakenaka, MD, PhD, Hiroyasu Soeda, MD, Takashi Okafuji, MD, Hidetake Yabuuchi, MD, PhD, Satoshi Shiokawa, MD, PhD, Junji Nishimura, MD, PhD and Hiroshi Honda, MD, PhD

1 From the Department of Clinical Radiology, Graduate School of Medical Sciences (M.H., H.S., T.O., H.Y., H.H.), and Department of Immunology and Neuroscience, Medical Institute of Bioregulation (S.S., J.N.), Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, Japan. From the 2004 RSNA Annual Meeting. Received October 6, 2004; revision requested December 15; revision received January 21, 2005; accepted February 21. Supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Sciences (no. 15500365). Address correspondence to M.H. (e-mail: mhatake{at}radiol.med.kyushu-u.ac.jp).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Purpose: To determine whether muscle fiber atrophy associated with steroid myopathy can be detected with T2 relaxation time.

Materials and Methods: Animal and human studies were approved by the ethics committee. Informed consent was obtained. Twelve rabbits were divided into a group that received 3 mg/kg of triamcinolone subcutaneously each day for 10 consecutive days (n = 6) and a control group that received saline (n = 6). Magnetic resonance (MR) imaging was performed before and after treatment. T2 and fat deposition ratio (FDR) of soleus and gastrocnemius muscles before and after treatment and between control rabbits and rabbits treated with steroids were compared by using two-way repeated analysis of variance and Bonferroni post hoc test to evaluate effects of steroid treatment. After imaging, rabbits were sacrificed. Extracellular space ratio (ECSR) and fiber diameter were examined. Correlation among T2, ECSR, and diameter of type 2 muscle fibers was analyzed with a Pearson correlation test with Bonferroni correction in gastrocnemius to determine factors affecting T2. In humans, T2 relaxation time and FDR of both muscles were compared between volunteers not treated with steroids and patients treated with steroids by using an unpaired t test to evaluate the effects of steroids.

Results: In rabbits, T2 of gastrocnemius muscle was significantly (P < .01) longer after steroid treatment than before steroid treatment and was also significantly (P < .01) longer than after saline administration. T2 of the gastrocnemius showed no significant difference in control rabbits before or after saline administration or in control rabbits and rabbits before steroid administration. T2 of the soleus muscle or FDR of either muscle showed no significant difference. There was a significant correlation (P < .01) among T2, ECSR, and diameter of type 2 muscle fibers in the gastrocnemius. In humans, T2 of the gastrocnemius was significantly (P < .01) longer in patients than in volunteers. T2 of the soleus or FDR of either muscle showed no significant difference.

Conclusion: Muscle fiber atrophy associated with steroid myopathy is detectable as prolongation of T2 relaxation time in the gastrocnemius muscle; the authors believe prolongation of T2 relaxation time is mainly due to increased ECSR reflecting type 2 muscle fiber atrophy.

© RSNA, 2005


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
There are two distinct types of steroid myopathy: acute and chronic. The acute type of steroid myopathy is a rare complication of short-term treatment with high doses of steroids, and it is characterized by generalized muscle atrophy and rhabdomyolysis involving the respiratory system (1). The chronic type of steroid myopathy occurs after prolonged treatment with moderate doses of steroids, and it has a clinical feature of gradual onset of weakness in proximal limb muscles (1). Respiratory insufficiency due to diaphragm muscle weakness is one of the critical complications of steroid treatment (1–4). In animal studies, selective atrophy of fast-twitch (hereafter, type 2) muscle fibers has been reported (3,5–8). Almost the same result (ie, type 2 muscle fiber atrophy) has been reported in humans with chronic steroid myopathy (3,4).

Many studies of muscle physiology have been performed with use of magnetic resonance (MR) imaging and relaxation times. Several studies have shown that T2 relaxation time of slow-twitch muscle is longer than that of fast-twitch muscle (9–11). T2-weighted MR imaging has been reported to be useful in the evaluation of denervated and reinnervated muscles (12). T2 relaxation time has also been reported to be useful in the determination of the effects of aging on fast-twitch muscle (13). A similar physiologic mechanism, atrophy of type 2 muscle fibers, has been associated with both steroid myopathy and aging (14–17). Thus, the purpose of our study was to determine whether muscle fiber atrophy due to steroid myopathy can be detected with use of T2 relaxation time.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Animals and Treatment
This animal study was approved by the Committee on Animal Experimentation at Kyushu University Hospital at Beppu (Beppu, Japan). Twelve female Japanese albino rabbits (weight, 3.5–4.5 kg) were divided into two groups. Six rabbits were used as control subjects, and six were treated with steroids. In the group treated with steroids, the first MR examination was performed before treatment; thereafter, 3 mg of triamcinolone per kilogram of body weight was injected subcutaneously each day for 10 consecutive days. The second MR examination was performed within 2 days after completion of steroid injection, and rabbits were sacrificed with an intravenous injection of an overdose of sodium pentobarbital for histopathologic analysis. In the control group, the same procedures were followed, except a corresponding volume of physiologic saline rather than steroid was injected. The dose, frequency, and duration of triamcinolone treatment were determined by referring to previous reports (6,8). One author (M.H.) performed all animal procedures.

Animal MR Examinations and Evaluation
MR examinations were performed by using a 1.5-T whole-body MR imaging system (Signa; GE Medical Systems, Milwaukee, Wis) with a head coil. Images were obtained by using a two-dimensional spin-echo pulse sequence to measure T2 relaxation time and a fast multiplanar gradient-echo pulse sequence with transverse magnetization spoiling to measure fat deposition. Imaging parameters were as follows: matrix, 256 x 128; section thickness, 5 mm; section gap, 1 mm; and field of view, 16 cm.

Rabbits were anesthetized with an intravenous injection of sodium pentobarbital (approximately 50 mg of sodium pentobarbital per kilogram of body weight). Rabbits were then placed in a decubitus position, and transverse images of the hind legs were obtained. To determine the T2 relaxation time, a spin-echo sequence with a repetition time of 2000 msec and echo times of 25, 50, 75, and 100 msec were used. One signal was acquired, and the examination lasted 4 minutes 40 seconds.

T2 relaxation time was calculated with the following method: Regions of interest (ROIs) were designated in both the soleus and the gastrocnemius muscles of the right or left hind leg by two authors working in consensus (M.H. and H.S., both with more than 10 years of experience in musculoskeletal MR imaging) and by avoiding apparent vascular structures or adipose tissue. We chose the gastrocnemius muscle (rich in type 2 muscle fiber) to represent fast-twitch muscle and the soleus muscle (rich in slow-twitch [hereafter, type 1] muscle fiber) to represent slow-twitch muscle because the predominant fiber type of these muscles has been determined in physiologic studies (18–21) and because the two muscles can be seen adjacent to one another on a single transverse MR image. The extent of each ROI was 4–8 mm2 and included 5–10 pixels.

Signal intensity of the ROIs was fitted to the following equation: SI = Me–TE/T2 + A, where SI is the measured signal intensity, Me is the steady-state magnetization, TE is the echo time, T2 is the T2 relaxation time, and A is the noise intensity. The T2 relaxation time was calculated by using a software program (Prism, version 3.02; Graph Pad Software, San Diego, Calif) (13). A representative image is shown in Figure 1. To evaluate fat deposition—which affects T2 relaxation time—in the muscle tissue, chemical shift imaging was performed by using a fast multiplanar gradient-echo sequence with transverse magnetization spoiling, repetition time of 150 msec, echo times of 4.2 msec for in-phase images and 6.3 msec for out-of-phase images, flip angle of 45°, acquisition of two signals, and bandwidth of 15.6 kHz (13,22). Two images (one in-phase image and one out-of-phase image) were obtained sequentially. Transmitter gain and receiver gain were kept constant. The examination duration was 40 seconds. To evaluate the amount of fat deposition, the fat deposition ratio (FDR) was calculated as follows: FDR = Sout/Sin, where Sout is the measured signal intensity of the ROI in the out-of-phase image and Sin is that in the in-phase image. The same ROIs were used to calculate FDR and measure the T2 relaxation time.



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  		Figure 1a: Representative transverse spin-echo MR images (repetition time msec/echo time msec, 2000/25) obtained in a rabbit (a) before and (b) after steroid treatment. The ROIs (1 and 2) are designated to enable calculation of the T2 relaxation time of the soleus and gastrocnemius muscles, respectively.

 


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  		Figure 1b: Representative transverse spin-echo MR images (repetition time msec/echo time msec, 2000/25) obtained in a rabbit (a) before and (b) after steroid treatment. The ROIs (1 and 2) are designated to enable calculation of the T2 relaxation time of the soleus and gastrocnemius muscles, respectively.

 
Animal Histopathologic Analysis
Rabbits were sacrificed within 3 days after the second MR imaging examination. The soleus and gastrocnemius muscles were dissected carefully and divided along the long axis into several pieces. The diameter of each muscle specimen was approximately 5 mm. The muscle specimens were instantly frozen in liquid nitrogen and stored at –85°C. Serial transverse 10-µm-thick sections were cut with a cryostat and stained with hematoxylin-eosin and nicotinamide adenine dinucleotide tetrazolium reductase (13). More than two slides were made for each stain of each muscle.

The extracellular space ratio (ECSR [the ratio of the amount of extracellular space to the combined amount of intracellular plus extracellular space]), the minimum diameter of type 1 and type 2 muscle fibers, and the fiber number ratio (FNR [the ratio of the number of type 2 muscle fibers to the number of total muscle fibers]) were measured with a public domain image processing and analysis program (NIH Image, version 1.63; National Institutes of Health, Bethesda, Md). Two or more visual fields with x200 magnification were randomly chosen from different parts of the slides of each muscle and evaluated. As there was a difference in density between extracellular spaces and cytoplasm of the muscle fibers (Fig 2), the density section option of this software program was used to calculate ECSR. First, the density range that covered the extracellular space was chosen carefully, and the extent of the extracellular space was measured. Second, the density range was widened to include all visual fields, and the extent of all visual fields was also measured. Two or more visual fields were evaluated for each muscle, and the mean value of ECSR was recorded for each muscle.



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  		Figure 2a: Representative photomicrographs of histologic specimens of the gastrocnemius muscle obtained in (a) control rabbits and (b) rabbits treated with steroids. The extracellular space is greater in rabbits treated with steroids than in control rabbits. (Hematoxylin-eosin stain; original magnification, x100.)

 


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  		Figure 2b: Representative photomicrographs of histologic specimens of the gastrocnemius muscle obtained in (a) control rabbits and (b) rabbits treated with steroids. The extracellular space is greater in rabbits treated with steroids than in control rabbits. (Hematoxylin-eosin stain; original magnification, x100.)

 
To measure muscle fiber diameter, a center point of the fiber was set with the naked eye, and the minimum diameter (the shortest diameter passing the center point) of each fiber was measured with the software program. More than 30 fibers in each muscle were examined, and the mean value was recorded as the fiber diameter of each muscle. For FNR measurement, more than 100 fibers in each muscle were counted. The value of FNR was recorded for each muscle. Hematoxylin-eosin and nicotinamide adenine dinucleotide tetrazolium reductase–stained sections were used for the study of ECSR and for the study of fiber diameter and FNR, respectively.

Findings at histopathologic analysis that were indicative of rhabdomyolysis or abnormal cells were also examined. Histopathologic evaluation was performed by two authors in consensus without treatment information (M.H. and H.S., with 3 and 4 years of pathology experience, respectively). Histopathologic analysis has been used in previous physiologic studies to evaluate both fiber numbers and fiber diameters, as well as extracellular spaces (14–17).

Human Participants
This human study was approved by the Committee on Clinical Study at Kyushu University Hospital at Beppu. Sixty-one consecutive patients were admitted to the Department of Immunology and Neuroscience in our hospital to undergo steroid treatment between October 2003 and March 2004. Among them, patients older than 60 years; those having a history of bone, joint, cardiovascular, or neuromuscular disease; and those having problems that precluded MR examination were excluded.

Three female patients gave their consent after the nature of the study had been fully explained, and they participated in the study: One 58-year-old woman had idiopathic thrombocytopenic purpura, one 30-year-old woman had systemic lupus erythematosus, and one 39-year-old woman had malignant lymphoma. All three women presented with muscle weakness, and all were clinically suspected of having steroid myopathy. The cumulative prednisolone doses and medication periods were 3150 mg and 3 months, 8140 mg and 15 months, and 2500 mg and 3 months, respectively. Other medications were used, as follows: (a) famotidine, sennoside, sodium risedronate hydrate, and probucol in the first patient; (b) magnesium oxide, roxatidine acetate hydrochloride, teprenone, alprazolam, sodium risedronate hydrate, and sodium ferrous citrate in the second patient; and (c) teprenone, rituximab, vincristine sulfate, pirarubicin hydrochloride, and cyclophosphamide in the third patient.

The muscle strength of patients was graded by two authors working in consensus (S.S. and J.N., both with more than 20 years of neurology experience) according to the Muscle Research Council grading of strength (23). Serum lactate dehydrogenase values were within the normal range in all three patients. Urine creatine values were not measured.

Subjects who were considered to be in good health at annual medical examinations performed at our institute or because of their past history and findings at physical examination were recruited during the same period. Among them, subjects older than 60 years; subjects with a history of bone, joint, cardiovascular, or neuromuscular disease; subjects with problems that precluded MR examination; and subjects with a history of exercise on a regular basis in the past 3 years were excluded. Male subjects were excluded because all subjects who underwent steroid treatment were female.

Eleven healthy female volunteers (age range, 32–58 years), most of whom were members of our hospital staff, gave informed consent after the nature of the study had been fully explained and agreed to participate in the study. An age limitation was set for the study because it was reported that T2 relaxation time of the gastrocnemius muscle is significantly longer in subjects older than 60 years than in subjects younger than 60 years (13).

Human MR Examinations and Evaluation
MR imaging was performed with the same system, except a knee coil was used. Images were obtained by using a two-dimensional spin-echo pulse sequence to measure T2 relaxation time and a fast multiplanar gradient-echo pulse sequence with transverse magnetization spoiling to measure fat deposition, with a 256 x 128 matrix, a 7-mm section thickness, a 3-mm section gap, and a 20-cm field of view. After resting for 15–20 minutes, subjects were placed in the supine position. Transverse contiguous images of the right leg were obtained from the knee to the ankle to determine the best single transverse section for displaying the soleus and gastrocnemius muscles. The T2 relaxation time and FDR of the right soleus and gastrocnemius muscles were measured for each subject. The methods used to measure T2 relaxation time and FDR were almost the same as those used in the animal study. However, an inversion-recovery sequence with a repetition time of 4500 msec; echo times of 25, 50, 75, and 100 msec; and an inversion time of 150 msec were used to measure T2 relaxation time. The inversion time was chosen to minimize the signal intensity from fat. One signal was acquired, and the examination duration was 10 minutes 30 seconds. ROIs were set by two authors working in consensus (M.H. and H.S.). The extent of each ROI was 20–30 mm2 and included 16–25 pixels. Inversion-recovery sequences were not used in the animal study because of a low signal-to-noise ratio.

Statistical Analysis
All statistical processing was performed with Statview, version 5.0, software (Hulinks, Tokyo, Japan) by four of the authors in consensus (M.H., H.S., T.O., and H.Y.). All results are expressed as means ± standard deviations, unless stated otherwise. In the animal experiment, T2 relaxation time and FDR of the soleus and gastrocnemius muscles were compared before and after treatment and between control rabbits and rabbits treated with steroids by using a two-way repeated analysis of variance and the Bonferroni post hoc test to determine whether the steroid treatment affected T2 relaxation time, fat deposition, or both. The relationship between the change in T2 relaxation time (T2 relaxation time after treatment minus T2 relaxation time before treatment) and the change in FDR (FDR after treatment minus FDR before treatment) was analyzed with the Pearson correlation test in the gastrocnemius muscle to evaluate the effect of fat deposition on T2 relaxation time change. ECSR, fiber diameter, and FNR of the soleus and gastrocnemius muscles were compared between control rabbits and rabbits treated with steroids by using an unpaired t test to determine the histopathologic changes associated with steroid treatment. The relationships between (a) T2 relaxation time after treatment and ECSR, (b) T2 relaxation time after treatment and the diameter of type 2 muscle fibers, and (c) ECSR and the diameter of type 2 muscle fibers were analyzed with the Pearson correlation test, with use of the Bonferroni correction, in the gastrocnemius muscle to evaluate the factors that affect T2 relaxation time. Prior to the start of the animal study, we estimated a linear correlation coefficient of about 0.8 between T2 and ECSR according to the previous study (13). Assuming a two-sided {alpha} value of .01 and a power of 80%, our study population had to include a total of approximately nine rabbits on the basis of the linear-correlation coefficient table. We decided that each group should include six rabbits; thus, we added one rabbit to each group in case a rabbit did not survive until the completion of the study.

In the human study, T2 relaxation time and FDR of the soleus and gastrocnemius muscles were compared between volunteers and patients who received steroids by using an unpaired t test to determine whether the steroid treatment affected T2 relaxation time, fat deposition, or both.

A P value of less than .01 was considered to indicate a statistically significant difference. The statistical analysis procedures were chosen in consultation with a statistician.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
Regarding results of the animal experiments (Tables 1, 2), T2 relaxation time of the gastrocnemius muscle was significantly longer (P < .01) in rabbits after treatment with steroids than before treatment with steroids. T2 relaxation time of the gastrocnemius muscle was significantly longer (P < .01) after treatment with steroids than after administration of saline. However, T2 relaxation time of the gastrocnemius muscle showed no significant difference between values obtained before administration of saline and values obtained after administration of saline in control rabbits or between values obtained in rabbits prior to administration of saline and values obtained in rabbits prior to steroid treatment (Table 1).


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  		Table 1. Comparison of T2 Relaxation Time and FDR in Rabbits

 

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  		Table 2. Comparison of ECSR, Fiber Diameter, and FNR

 
T2 relaxation time of the soleus muscle or FDR of either the soleus or the gastrocnemius muscle showed no significant difference. There was no significant correlation between the change in T2 relaxation time and the change in FDR (r = 0.006, P = .986) in the gastrocnemius muscle. ECSR of the gastrocnemius muscle was significantly greater (P < .01) in rabbits treated with steroids than in control rabbits (Table 2, Fig 2). ECSR of the soleus muscle showed no significant difference between control rabbits and rabbits treated with steroids. The diameter of type 2 muscle fibers in the gastrocnemius muscle was significantly smaller (P < .01) in rabbits treated with steroids than in control rabbits (Table 2). Neither the diameter of type 1 muscle fibers in the soleus or gastrocnemius muscles nor the FNR of the gastrocnemius muscle was significantly different between control rabbits and rabbits treated with steroids. Type 2 muscle fibers were not detected in the soleus muscle. There was a significant correlation (P < .01) between (a) T2 relaxation time and ECSR (r = 0.813) (Fig 3), (b) T2 relaxation time and the diameter of type 2 muscle fibers (r = 0.758), and (c) ECSR and the diameter of type 2 muscle fibers (r = 0.777) in the gastrocnemius muscle. Findings were normal, with the exception of type 2 muscle fiber atrophy in the gastrocnemius muscle of rabbits treated with steroids.



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  		Figure 3: Scatterplot of T2 relaxation time versus ECSR in the gastrocnemius muscle. T2 relaxation time correlates well with ECSR. The r and P values are 0.813 and .0013, respectively. {circ} = control rabbits, {bullet} = rabbits treated with steroids.

 
In the human study, T2 relaxation time of the gastrocnemius muscle was significantly longer (P < .01) in patients treated with steroids than in volunteers (Table 3). However, T2 relaxation time of the soleus muscle showed no significant difference between volunteers and patients. There was no significant difference in FDR, either in the soleus muscle or in the gastrocnemius muscle, between volunteers and patients. Muscle strength was graded as 4 for all patients.


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  		Table 3. Comparison of T2 Relaxation Time and FDR in Humans

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
Results from our animal study show that muscle fiber atrophy associated with steroid myopathy can be detected by using the T2 relaxation time of the gastrocnemius muscle. T2 relaxation time of the gastrocnemius muscle showed a significant increase in rabbits treated with steroids, but it showed no significant difference in control rabbits.

We were concerned that differences of fat deposition in muscles may have affected the results; thus, we measured FDR. However, FDR showed no significant change between pre- and posttreatment status. There was no significant correlation (r = 0.006) between the change in T2 relaxation time and the change in FDR in the gastrocnemius muscle. We concluded, therefore, that differences of fat deposition in muscles did not cause prolongation of T2 relaxation time. Although FDR is not used to measure fat fraction directly and other factors—such as susceptibility effects, differential T2 relaxation time, and gross chemical shift—might have influenced the FDR values, we considered these factors to have had a slight or negligible effect. Histopathologic analysis showed that the ECSR of the gastrocnemius muscle was significantly greater in subjects treated with steroids than in control subjects and that the diameter of type 2 muscle fibers in the gastrocnemius muscle was significantly smaller in subjects treated with steroids than in control subjects. We presume that the prolongation of T2 relaxation time is mainly due to the increase in ECSR because T2 relaxation time of extracellular fluid is about four times longer than that of intracellular fluid in muscle tissue (12,24), and atrophic change of type 2 muscle fibers is the primary cause of the increase in ECSR. The significant correlations (P < .01) between (a) T2 relaxation time and ECSR, (b) T2 relaxation time and diameter of type 2 fibers, and (c) ECSR and diameter of type 2 fibers in the gastrocnemius muscle support our hypothesis.

The mechanisms of prolongation of T2 relaxation time in steroid myopathy are similar to those in aging and denervation. Kikuchi et al (12) reported that increased signal intensity on T2-weighted images and prolongation of T2 relaxation time in denervated muscles can be attributed to an increase in extracellular fluid spaces. Hatakenaka et al (13) reported that T2 relaxation time of fast-twitch muscle fiber increases as age increases, mainly because of increased extracellular space, which reflects age-related atrophy of type 2 muscle fibers. Although it was possible that muscle cells that were abnormal because of steroid treatment may have contributed to the prolongation of T2 relaxation time, no abnormal findings—with the exception of atrophy of type 2 muscle fibers—were observed in the gastrocnemius muscle of subjects treated with steroids. A change in total water content, which we did not measure in this study, might have affected T2 relaxation time. We believe, however, that this is unlikely or is not the main reason for prolongation of T2 relaxation time because it has been reported that total water content is unchanged in denervated muscles, despite the fact that signal intensity on T2-weighted images and T2 relaxation time increase (12).

In our human study, we were concerned that the different methods of steroid administration between the animal and human studies might have affected the results. Chronic steroid myopathy in humans who undergo steroid treatment may be different from that in animals that undergo steroid treatment. However, the results from the human study were in concordance with those from the animal experiment. One of the problems was the uncertainty of whether the prolongation of T2 relaxation time in the gastrocnemius muscle observed in patients was attributable to steroid treatment. Other factors, such as bed rest, may have affected the results. We believe, however, that this is unlikely, since bed rest has been reported to affect soleus muscle fibers instead of gastrocnemius muscle fibers and to result in atrophy of type 1 muscle fibers (25,26). Other problems were the fact that the number of patients and volunteers was small and the potential influence of other drugs (eg, anticancer drugs) on T2 relaxation time of muscles. Further studies will be needed to clarify details, and attention should be paid to extrapolate the findings in animal experiments to the findings in human studies.

FNR was not considered to be the reason for the change in T2 relaxation time. Kuno et al (27,28) reported that there is a positive relationship between T2 relaxation time and the ratio of type 2 muscle fibers; therefore, we examined FNR. No significant difference in FNR of the gastrocnemius muscle between the control rabbits and the rabbits treated with steroids was observed, and the effect size was small. No type 2 muscle fiber was detected in the soleus muscle in our experiments; this result was consistent with the findings of previous studies (18,19).

According to our presumption that the change in T2 relaxation time was mainly due to the change in ECSR, T2 relaxation time of the soleus muscle would not be affected because ECSR and fiber diameter of the soleus muscle were unaffected in rabbits treated with steroids. T2 relaxation time of the soleus muscle showed no significant change. FDR of the soleus muscle also showed no significant change.

We believe that our results concerning the change in fiber diameter and fiber distribution associated with steroid treatment are valid because they are consistent with the findings of previous studies. Steroids have been found to cause atrophy of type 2 muscle fibers (4–6,8), but they do not affect either the cross-sectional area of type 1 muscle fibers or fiber proportions (7).

Our study has some limitations. We used four echo times (ie, 25, 50, 75, and 100 msec) to measure T2 relaxation time, which was the maximum number of settings available on our MR system. The accuracy of the absolute T2 relaxation time value obtained with this method may be limited when compared with other methods that make use of multiple echo times. However, it is still possible to compare T2 relaxation time values obtained with our method, regardless of the accuracy of the absolute values. Inversely, our method of measuring T2 relaxation time requires no specific application; thus, it is suited to most clinical MR imaging systems. This may be an advantage for clinical practice. Another limitation of our study was that the number of volunteers and patients who received steroids was small. Further study will be needed to draw definitive conclusions about the clinical usefulness of T2 relaxation time in the evaluation of steroid myopathy.

Measurement of muscle force is a useful method in the evaluation of muscle function, and it may provide useful information on steroid myopathy. Such measurement, however, includes subjective factors. Measuring muscle force objectively is especially difficult in elderly people or patients with joint pain. Although histopathologic examination of muscle specimens is an objective method, muscle biopsy is an invasive procedure, and repeated examination or biopsy of several muscles would be difficult to perform. MR imaging may provide objective information for each muscle regarding the muscle fiber atrophy associated with steroid myopathy; this information cannot be obtained by measuring muscle force or urine creatine levels, and the noninvasive nature of this modality allows for repeat follow-up examinations. Our method of measuring T2 relaxation time requires no specific application; thus, it may be suited to any hospital with a clinical MR imaging system.

In conclusion, our results suggest that muscle fiber atrophy associated with steroid myopathy in type 2 muscle fibers can be detected by determining T2 relaxation time in the gastrocnemius muscle and that prolongation of T2 relaxation time is probably associated with an increase in extracellular spaces that reflects atrophy of type 2 muscle fibers.


   ACKNOWLEDGMENTS
 
We thank Tomomi Yamada, MS, a medical statistician at Kyushu University Hospital, for her guidance in performing the statistical analysis.


   FOOTNOTES
 

Abbreviations: ECSR = extracellular space ratio • FDR = fat deposition ratio • FNR = fiber number ratio • ROI = region of interest

Authors stated no financial relationship to disclose.

Author contributions: Guarantors of integrity of entire study, M.H., H.H.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, M.H., H.Y., H.H.; clinical studies, M.H., H.S., S.S., J.N.; experimental studies, M.H., H.S., T.O.; statistical analysis, M.H., H.S., T.O., H.Y.; and manuscript editing, M.H., H.Y., H.H.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

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