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Published online before print March 27, 2008, 10.1148/radiol.2472070403
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(Radiology 2008;247:409-417.)
© RSNA, 2008

Experimental Studies

Peripheral Nerve Injury: Diagnosis with MR Imaging of Denervated Skeletal Muscle—Experimental Study in Rats1

Eiko Yamabe, MD, Toshiyasu Nakamura, MD, PhD, Koichi Oshio, MD, PhD, Yoshito Kikuchi, MD, PhD, Hiroyasu Ikegami, MD, PhD, and Yoshiaki Toyama, MD, PhD

1 From the Departments of Orthopaedic Surgery (E.Y., T.N., Y.K., H.I., Y.T.) and Diagnostic Radiology (K.O.), School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Received February 28, 2007; revision requested May 9; revision received July 17; accepted August 17; final version accepted October 8. Supported by the General Insurance Association of Japan. Address correspondence to T.N. (e-mail: tosiyasu{at}sc.itc.keio.ac.jp).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Purpose: To prospectively evaluate signal intensity change on T2-weighted magnetic resonance (MR) images and the time course of T2 values and T2 ratios after reinnervation in various nerve injury models in rats.

Materials and Methods: Institutional animal use and care committee approval was obtained. Thirty male rats made up four groups of rats with an injured left posterior tibial nerve (irreversible neurotmesis, reversible neurotmesis, severe axonotmesis, or moderate axonotmesis) and one control group. There were six rats in each group. Signal intensity changes were seen in the gastrocnemius muscle on the T2-weighted MR images. T2 values were also measured in vivo with the Carr-Purcell-Meiboom-Gill method. Gait function was assessed by calculating the print length factor (PLF). T2 ratios and PLFs on the injured side were compared with those on the unaffected side. Ratios of specific acquisition points within groups were compared by using repeated-measures analysis of variance. Comparisons across the five groups at each acquisition point were performed by using one-way analysis of variance with Scheffe post hoc testing. P < .05 indicated a significant difference.

Results: The more severe the nerve damage, the higher the signal intensity on T2-weighted MR images. There were significant differences in T2 ratios between the nerve injury groups and the control group (P < .05). Changes in T2 values and ratios depended on the degree of nerve injury. In the reversible neurotmesis group, T2 values and ratios began to decrease 28 days after surgery. In the severe and moderate axonotmesis groups, T2 values and ratios began to decrease 14 days after surgery. The starting point of functional recovery also depended on the degree of nerve injury.

Conclusion: The degree and prognosis of nerve injury can be evaluated by observing changes in signal intensity on T2-weighted images and the time course of T2 values and ratios.

© RSNA, 2008


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Electromyography (EMG) is a useful tool for diagnosing peripheral nerve injury. The M wave produced by stimulating the nerve at a site proximal to the injured point disappears 4–5 days after the injury. Needle EMG reveals the fibrillation potential or positive sharp wave in the target denervated muscle within 3 weeks after nerve damage in humans and within 1 week after nerve damage in rats (1). However, EMG is associated with some difficulties in the detection of denervated skeletal muscle because it is both invasive and dependent on the skill of the examiner. It is relatively difficult to obtain information that is useful, objective, and reproducible with EMG in children and in situations where the muscle being examined is in a deep location.

Unlike EMG, magnetic resonance (MR) imaging is a noninvasive diagnostic imaging tool that is not reliant on the experience of the examiner. Bryan et al (2) showed that there was a negative correlation between tibialis anterior compound muscle action potential amplitude and muscle T2 in patients with amyotrophic lateral sclerosis, and they concluded that T2 was the best indicator of motor neuron dysfunction. This information is useful in the diagnosis of peripheral nerve injury because T2-weighted MR imaging of denervated skeletal muscle reveals high signal intensity (3–6), which may result from an increase in the extracellular fluid space (3,7). However, the relationship between degree of peripheral nerve injury and signal intensity has yet to be considered fully. The relationship between function and recovery pattern of signal intensity also remains unknown. Knowledge of this relationship may be helpful when predicting the degree and prognosis of peripheral nerve injury. The purpose of our study was to prospectively evaluate signal intensity change on T2-weighted MR images and the time course of T2 values and T2 ratios after reinnervation in various nerve injury models in rats.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Our study was financially supported by a special grant from the General Insurance Association of Japan for the study of trauma after a traffic accident. The authors had control of the data and the information included in this article.

Experimental Model
We used a total of 30 male Wistar rats, each of which weighed approximately 200 g. The study was approved by our institutional animal use and care committee. The rats were anesthetized with 45 mg of pentobarbital (Nembutal; Abbott Laboratories, North Chicago, Ill) per kilogram of body weight injected intraperitoneally. During microscopic surgery, we created four nerve injury models in the left posterior tibial nerves. There were six rats in each group. In the irreversible neurotmesis model (group A), we transected the nerve and tightly ligated the proximal stump with 5-0 nylon stitches to permanently prevent repair. In the reversible neurotmesis model (group B), we transected the nerve and immediately sutured it with 10-0 nylon stitches. In the severe axonotmesis model (group C), we clipped the nerve for 30 minutes, whereas we clipped the nerve for only 15 minutes in the moderate axonotmesis model (group D). An intracranial aneurysm clip with a closing force of 1.38 N was used (Sugita titanium aneurysm clip mini; Mizuho, Tokyo, Japan) (8,9). We simultaneously performed sham operations (incision and exploration of the nerve only) in the control group (group E, six rats). All surgical procedures were performed by an author (E.Y.) who had 6 years of experience with microsurgical procedures. We performed image acquisition, measurement of T2 values, functional assessment, and EMG studies 3 and 5 days after surgery and 1, 2, 3, 4, 6, 8, 10, and 12 weeks after surgery.

MR Image Acquisition and Evaluation
We anesthetized the six rats in each of the five groups with pentobarbital before fixing them in the prone position on a special mount by holding their fore and hind feet. We obtained MR images of the gastrocnemius muscle, which is the target muscle of the posterior tibial nerve, by using a 1.5-T clinical MR unit (Signa Excite HD, version 12; GE Medical Systems, Milwaukee, Wis). The rats were positioned on a round 3-inch-diameter surface coil, and transverse T2-weighted fast spin-echo images were obtained by using the following sequence parameters: 4000/104 (repetition time msec/echo time msec), 3.0-mm section thickness, 10-cm field of view, and 256 x 256 matrix. We subjectively classified the various signal intensity changes in the denervated gastrocnemius muscle into the following three grades: grade 1, signal was iso- or slightly hyperintense (Fig 1a) compared with that in the control group (Fig 1d); grade 2, intermediate to high signal intensity (Fig 1b) compared with that in the control group; and grade 3, high signal intensity (Fig 1c) compared with that in the control group. Three authors (E.Y., Y.K., and T.N.; 10, 17, and 20 years of experience with musculoskeletal MR imaging, respectively) evaluated the images in consensus.


Figure 1A
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  		Figure 1a: Transverse T2-weighted MR images (4000/104) of the left gastrocnemius muscle obtained with rats in the prone position. (a) Image shows grade 1 signal intensity (ie, signal intensity was isointense or slightly hyperintense compared with that in the control group). (b) Image shows grade 2 signal intensity (ie, intermediate to high signal intensity compared with that in the control group). (c) Image shows grade 3 signal intensity (ie, high and homogeneous signal intensity compared with that in the control group). (d) Image shows the normal signal intensity in a control rat (outlined). A = anterior, L = lateral, M = medial, P = posterior.

 

Figure 1B
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  		Figure 1b: Transverse T2-weighted MR images (4000/104) of the left gastrocnemius muscle obtained with rats in the prone position. (a) Image shows grade 1 signal intensity (ie, signal intensity was isointense or slightly hyperintense compared with that in the control group). (b) Image shows grade 2 signal intensity (ie, intermediate to high signal intensity compared with that in the control group). (c) Image shows grade 3 signal intensity (ie, high and homogeneous signal intensity compared with that in the control group). (d) Image shows the normal signal intensity in a control rat (outlined). A = anterior, L = lateral, M = medial, P = posterior.

 

Figure 1C
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  		Figure 1c: Transverse T2-weighted MR images (4000/104) of the left gastrocnemius muscle obtained with rats in the prone position. (a) Image shows grade 1 signal intensity (ie, signal intensity was isointense or slightly hyperintense compared with that in the control group). (b) Image shows grade 2 signal intensity (ie, intermediate to high signal intensity compared with that in the control group). (c) Image shows grade 3 signal intensity (ie, high and homogeneous signal intensity compared with that in the control group). (d) Image shows the normal signal intensity in a control rat (outlined). A = anterior, L = lateral, M = medial, P = posterior.

 

Figure 1D
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  		Figure 1d: Transverse T2-weighted MR images (4000/104) of the left gastrocnemius muscle obtained with rats in the prone position. (a) Image shows grade 1 signal intensity (ie, signal intensity was isointense or slightly hyperintense compared with that in the control group). (b) Image shows grade 2 signal intensity (ie, intermediate to high signal intensity compared with that in the control group). (c) Image shows grade 3 signal intensity (ie, high and homogeneous signal intensity compared with that in the control group). (d) Image shows the normal signal intensity in a control rat (outlined). A = anterior, L = lateral, M = medial, P = posterior.

 
T2 Values and Ratios
We examined T2 values in vivo by using the Carr-Purcell-Meiboom-Gill imaging sequence (10). A 3 x 3-pixel region of interest was positioned in the gastrocnemius muscle at the midlevel of the calf, and an effort was made to avoid including fatty septa and vessels in the voxel volume. Signal intensity was measured as an average of three measurement points in the region of the gastrocnemius muscle. Signal decay of the gastrocnemius muscle was measured with a stepped echo time (20–160 msec) in eight steps (20-msec echo spacing) and a fixed repetition time (2000 msec). Three authors (E.Y., T.N., and K.O.; all of whom had more than 10 years of experience with musculoskeletal MR imaging) performed T2 value examinations and T2 ratio analyses. T2 values were calculated by fitting the data to the following equation: S(TE) = S(0) · exp(–TE/T2), where S is signal intensity and TE is time to echo. We analyzed the ratios of the T2 values of the denervated gastrocnemius muscles with respect to the contralateral unaffected muscles because functional assessment was performed by comparing lower extremities in which experiments were performed with contralateral lower extremities in which experiments were not performed.

Functional Assessment
We compared paw length on the experimental side with that on the normal side and calculated the print length factor (PLF) to assess gait function (11). PLF was calculated with the following equation: PLF = (EPL – NPL)/NPL, where EPL is the experimental paw length and NPL is the normal paw length. Once the posterior tibial nerve was damaged, the lower extremity appeared as a flat foot, and the experimental paw length became longer than the normal paw length. One author (E.Y.) who had 10 years of experience with this functional assessment method performed the measurements.

EMG Study
In the electrophysiologic study, three rats randomly selected from each group were again anesthetized, and the sciatic nerve was exposed. The sciatic nerve (located proximal to the surgical site) and the posterior tibial nerve were stimulated with two monopolar needle electrodes. Another monopolar needle electrode was inserted into the belly of the lateral head of the gastrocnemius muscle. The reference electrode was placed in the distal tendon, with the ground electrode placed on the tail. We examined whether the M wave, which is the action potential of the muscle induced by electrical stimulation of the nerve, could be detected with an EMG device (Neuropack Four Mini; Nihon Kohden, Tokyo, Japan). An author (E.Y.) who had 10 years of experience with EMG performed the measurements.

Statistical Analysis
All data are presented as mean values ± standard deviations, and changes in T2 ratios and PLFs in the four injury groups and the control group were analyzed for significance. Ratios of specific acquisition points within groups were compared by using repeated-measures analysis of variance. Comparisons across the five groups at each acquisition point were performed by using one-way analysis of variance with the Scheffe post hoc test. A two-sided P value of less than .05 was considered to indicate a significant difference. We used the SigmaStat statistical program (version 3.1; Systat, Richmond, Calif).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Changes in Signal Intensity
In the irreversible neurotmesis group (group A), T2-weighted images showed intermediate to high signal intensity in the gastrocnemius muscle beginning 5 days after surgery, and they showed high signal intensity at 2-week follow-up. For all rats in this group, signal intensity remained high until 12-week follow-up (Table 1).


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  		Table 1. Classification of Signal Intensity Changes for Each Injury Group

 
In the reversible neurotmesis group (group B), the target gastrocnemius muscle displayed intermediate to high signal intensity on T2-weighted images obtained 5 days after surgery, and signal intensity became high at 2-week follow-up in all rats in this group. Signal intensity began to decrease to the intermediate level at 6–8-week follow-up (Table 1).

In the severe (group C) and moderate (group D) axonotmesis groups, intermediate to high signal intensity was seen on T2-weighted images obtained 5 days after surgery and remained until 4 weeks after surgery. At 4-week follow-up, signal intensity began to decrease gradually before it returned completely to grade 1 at 6-week follow-up in the moderate axonotmesis group and at 8-week follow-up in the severe axonotmesis group (Table 1).

T2 Values
In the irreversible neurotmesis group (group A), T2 values increased gradually until 4 weeks after surgery and remained high (approximately 40 msec) throughout the study period (Fig 2a). In the reversible neurotmesis group (group B), T2 values also increased gradually until 4 weeks after surgery; thereafter, they began to decrease (Fig 2b). In the axonotmesis injury models (groups C and D), T2 values increased gradually until 2 weeks after surgery, at which point they began to decrease, eventually reaching approximately 30 msec (Fig 2c, 2d). This value was almost identical to that of the gastrocnemius muscle in the control group at 12-week follow-up (Fig 2e).


Figure 2A
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  		Figure 2a: Graphs show T2 values for the (a) irreversible neurotmesis, (b) re-versible neurotmesis, (c) severe axonotmesis, (d) moderate axonotmesis, and (e) control groups.

 

Figure 2B
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  		Figure 2b: Graphs show T2 values for the (a) irreversible neurotmesis, (b) re-versible neurotmesis, (c) severe axonotmesis, (d) moderate axonotmesis, and (e) control groups.

 

Figure 2C
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  		Figure 2c: Graphs show T2 values for the (a) irreversible neurotmesis, (b) re-versible neurotmesis, (c) severe axonotmesis, (d) moderate axonotmesis, and (e) control groups.

 

Figure 2D
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  		Figure 2d: Graphs show T2 values for the (a) irreversible neurotmesis, (b) re-versible neurotmesis, (c) severe axonotmesis, (d) moderate axonotmesis, and (e) control groups.

 

Figure 2E
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  		Figure 2e: Graphs show T2 values for the (a) irreversible neurotmesis, (b) re-versible neurotmesis, (c) severe axonotmesis, (d) moderate axonotmesis, and (e) control groups.

 
T2 Ratios
The T2 ratio increased gradually until 4 weeks after surgery in the irreversible neurotmesis group (group A) and remained high (mean, approximately 1.33) throughout the remainder of the study period (Table 2). In this group, we observed significant increases in T2 ratios compared with those in the control group 5 days after surgery (P < .001). T2 ratios changed significantly during the periods from 3 days after surgery to 5 days after surgery (P < .001), from 5 days after surgery to 1 week after surgery (P < .001), and from 1 week after surgery to 3 weeks after surgery (P = .002).


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  		Table 2. T2 Ratios for Each Injury Group

 
In the reversible neurotmesis group (group B), T2 ratios increased gradually until 4 weeks after surgery; thereafter, they decreased gradually but did not completely return to normal, with a ratio of 1.065 ± 0.018 at 12-week follow-up (Table 2). T2 ratios were significantly higher in this group than in the control group 5 days after injury (P < .001). In this group, T2 ratios changed significantly during the periods from 3 days after surgery to 5 days after surgery (P < .001), from 5 days after surgery to 2 weeks after surgery (P < .001), from 4 weeks after surgery to 6 weeks after surgery (P < .001), and from 6 weeks after surgery to 10 weeks after surgery (P < .001).

In the severe axonotmesis group (group C), T2 ratios increased gradually until 2 weeks after surgery; thereafter, they decreased and were essentially normalized 6 weeks after surgery (Table 2). T2 ratios in the severe axonotmesis group were significantly higher than those in the control group during the periods from 5 days after surgery to 6 weeks after surgery (P < .001). T2 ratios changed significantly during the periods from 3 days after surgery to 5 days after surgery (P < .001), from 3 weeks after surgery to 4 weeks after surgery (P = .012), and from 4 weeks after surgery to 6 weeks after surgery (P = .019). After 6 weeks, there were no significant differences between T2 ratios in this group and those in the control group.

In the moderate axonotmesis group (group D), T2 ratios increased gradually until 2 weeks after surgery, at which point they decreased gradually, and they became almost normal 4 weeks after surgery (Table 2). There were significant differences between T2 ratios in this group and those in the control group from 1 week after surgery to 3 weeks after surgery (P < .001). In this group, T2 ratios changed significantly during the periods from 3 days after surgery to 2 weeks after surgery (P < .001), from 2 weeks after surgery to 3 weeks after surgery (P = .011) and from 3 weeks after surgery to 4 weeks after surgery (P = .028).

T2 ratios depended on the degree of nerve injury (Fig 3). (Injury was most severe in group A and least severe in group D.) There were significant differences between groups A, B, and D 2 weeks after surgery (P < .001); between groups B and C (P = .006) and C and D (P = .011) 3 weeks after surgery; between groups B and C (P < .001) 4 weeks after surgery; between groups A and B (P < .001), B and C (P < .001), and C and D (P = .02) 6 weeks after surgery; between groups A and B (P < .001) and B and C (P = .004) 8 weeks after surgery, and between groups A and B and groups B and C (P < .001) 10 weeks after surgery.


Figure 3
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  		Figure 3: Graph shows the time course of T2 ratio for each injury group. The T2 ratio depends on the degree of nerve injury. There were significant differences between the irreversible ({square}) and reversible ({blacksquare}) neurotmesis groups and the severe ({blacktriangleup}) and moderate (bullet) axonotmesis groups 3 weeks after surgery (P < .05). There were also significant differences between the irreversible neurotmesis group and the reversible neurotmesis group 6 weeks after surgery (P < .05). x = Control group, * = P < .001.

 
PLF Values
In the irreversible neurotmesis group (group A), PLFs remained high throughout the study period, with a mean of approximately 0.613 (Table 3). PLF values were significantly higher in group A than in the control group throughout the study (P < .001).


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  		Table 3. PLFs for Each Injury Group

 
In the reversible neurotmesis group (group B), PLFs remained high until 3 weeks after surgery, at which point they gradually decreased for the remainder of the study, and they eventually reached a mean value of 0.164 ± 0.06 at 12-week follow-up (Table 3). There were significant differences between the PLFs 3 days after surgery and the PLFs 4 weeks after surgery (P < .001), between the PLFs 5 days after surgery and the PLFs 2 weeks after surgery (P = .001), between the PLFs 1 week after surgery and the PLFs 4 weeks after surgery (P = .002), between the PLFs 3 weeks after surgery and the PLFs 6 weeks after surgery (P < .001), and between the PLFs 4 weeks after surgery and the PLFs 8 weeks after surgery (P < .001). Throughout the study period, the PLFs in group B increased significantly compared with the PLFs in the control group (P < .001).

In the severe axonotmesis group (group C), PLFs began to decrease rapidly 3 days after surgery before they returned to almost normal values at 1-week follow-up (0.188 ± 0.034) (Table 3). PLF values changed significantly during the period from 5 days after surgery to 1 week after surgery (P < .001) and from 2 weeks after surgery to 3 weeks after surgery (P = .003). There were significant differences between PLF values in this group and those in the control group at 3- and 5-day follow-up (P < .001 for differences at both follow-up periods).

PLFs in the moderate axonotmesis group (group D) also began to decrease rapidly 3 days after surgery, and they returned to a normal value at 1 week (0.188 ± 0.072) (Table 3). PLFs changed significantly during the period from 3 days to 5 days after surgery (P < .001), from 5 days to 1 week after surgery (P = .009), from 5 days to 2 weeks after surgery (P < .001), and from 1 week to 3 weeks after surgery (P < .001). There were significant differences between the PLF values in this group and those in the control group at 3- and 5-day follow-up (P < .001 for differences at both follow-up periods).

Regarding the time courses of PLFs in all groups (Fig 4), there were significant differences between group C and both group A and group B (P < .001) and between group D and both group A and group B (P < .001) at 3-day follow-up; between group C and both group A and group B (P < .001), between group D and both group A and group B (P < .001), and between groups C and D (P = .001) at 5-day follow-up; between group C and both group A and group B (P < .001) and between group D and both group A and group B (P < .001) at 1-week follow-up; and between groups A and B (P < .001) and between groups C and D and both group A and group B (P < .001) during the period from 2-week follow-up to the end of the study.


Figure 4
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  		Figure 4: Graph shows the time course of PLFs for each injury group. PLF depends on the degree of nerve injury. There were significant differences between the irreversible ({square}) and reversible ({blacksquare}) neurotmesis groups and the severe ({blacktriangleup}) and moderate (bullet) axonotmesis groups throughout the study period (P < .05). There were also significant differences between the irreversible neurotmesis group and the reversible neurotmesis group 2 weeks after surgery (P < .05). x = Control group, * = P < .001.

 
The time course of T2 ratios was compared with that of PLF values. The resulting graph is shown in Figure 5.


Figure 5
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  		Figure 5: Graphs show comparison of time courses between T2 ratios (top) and PLFs (bottom). If the T2 ratio in period 2 is lower than that in period 1, functional recovery is expected. If the T2 ratio in period 2 is almost identical to or higher than that in period 1, functional recovery is not expected. {square} = irreversible neurotmesis group, {blacksquare} = reversible neurotmesis group, bullet = moderate axonotmesis group, {blacktriangleup} = severe axonotmesis group.

 
EMG Study
No M waves were detected throughout the study period in the irreversible neurotmesis group (group A). In the reversible neurotmesis group (group B), M waves were detected 4 weeks after surgery; however, the waveforms showed temporal dispersion. Eight weeks after surgery, the shape of the M wave became biphasic and was almost identical to that seen in the normal state. M waves were detected at 2-week follow-up in the severe (group C) and moderate (group D) axonotmesis groups.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Although fat infiltration may be seen in chronic degenerative muscle (5), denervated skeletal muscle in the acute and subacute phases characteristically shows high signal intensity on T2-weighted MR images and normal signal intensity on T1-weighted MR images (3–6,12–15). This phenomenon might reflect an increase in extracellular fluid (3,7); however, to our knowledge, the relationship between degree of nerve injury and MR signal intensity is not yet completely understood.

In our study, changes in T2 values, T2 ratios, and PLFs among the various nerve injury models were dependent on the degree of injury. T2-weighted MR images had high signal intensity that started 1 week after surgery in the reversible neurotmesis group (group B) and 2 weeks after surgery in all the axonotmesis groups (groups C and D). For all injury models, no obvious increase in signal intensity on the T2-weighted MR images was observed within 1 week after surgery. In the case of severe nerve damage or irreversible neurotmesis, high-signal-intensity changes were seen on T2-weighted images over a long period. We believe that the degrees of morphologic and metabolic changes caused by denervation were influenced by the degree of nerve injury; therefore, we can detect differences in the degree of nerve injury by using T2 values and ratios at T2-weighted MR imaging, which reflect the extracellular fluid in the denervated target muscle.

In the reversible neurotmesis group (group B) and all axonotmesis groups (groups C and D), the functional recoveries indicated by PLFs occurred faster than the normalization of T2 ratios. Compared with EMG findings, the recovery point of the T2 ratio was almost identical to the detection of M waves in the reversible neurotmesis group and the axonotmesis groups. It may be possible to predict the prognosis of injury from the MR findings. We compared the time course of T2 ratios with that of PLFs, as shown in Figure 5, and we believe that the first critical point occurred 14 days after surgery, when T2 ratios began to decrease in the axonotmesis groups. The second critical point occurred 28 days after surgery, when T2 ratios recovered in the reversible neurotmesis group. We defined period 1 as the time between 14 and 28 days after surgery. This period was followed immediately by period 2. If the T2 ratios in period 2 were lower than those in period 1, we expected functional recovery; however, if the T2 ratios in period 2 were almost identical to or higher than those in period 1, functional recovery was not expected. In the latter case, surgical treatment, such as neurolysis, must be performed as soon as possible. Although there may be some differences in the process of nerve recovery between rats and humans, we consider our results to be consistent with those expected in human skeletal muscles.

We could not determine the degree of injury in the early period after initial injury, typically up to 1 week, although the damage and prognosis of the nerve injury could be predicted from long-term investigations of T2-weighted MR imaging, T2 values, and T2 ratios. High signal intensity of denervated muscle can be detected on T2-weighted MR images 2–8 weeks after injury (3,12–15). Further experimental study with use of recently developed techniques (ie, diffusion MR imaging, which depicts the acute increase of extracellular fluid better than does T2-weighted MR imaging) (16–20) is needed.

Our study had limitations. Rat skeletal muscles were used for sequential MR imaging, in vivo T2 measurements, functional assessments, and EMG studies. Furthermore, sacrifice of the animals was needed. Although there may be some differences in the process of nerve recovery between rats and humans, we consider the reported experiment results to be generally consistent with changes at MR imaging in human skeletal muscles.

Practical application: MR imaging can depict signal intensity changes directly and objectively. Denervated muscle shows high signal intensity on T2-weighted MR images. The more severe the nerve damage, the higher the T2 values and signal intensity on T2-weighted images. We can use MR findings to predict nerve damage. MR imaging is a noninvasive tool that can be used to diagnose peripheral nerve injury, and it is particularly useful when EMG is difficult to perform. Although further investigations are needed in human subjects, MR imaging—in addition to EMG—may enable the examination of denervated muscle.


   ADVANCES IN KNOWLEDGE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
IMPLICATION FOR PATIENT CARE
 References
 


   IMPLICATION FOR PATIENT CARE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
References
 


   ACKNOWLEDGMENTS
 
The authors thank Toshio Watanabe, Chief Technologist, Department of Radiology, School of Medicine, Keio University, for his assistance with image acquisition. We also thank Yukio Horiuchi, MD, PhD, Chief Director, Department of Orthopaedic Surgery, Kawasaki Municipal Hospital, for his advice during our study.


   FOOTNOTES
 

Abbreviations: EMG = electromyography • PLF = print length factor

See also Science to Practice in this issue.

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

See Materials and Methods for pertinent disclosures.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 

  1. Thesleff S, Ward MR. Studies on the mechanism of fibrillation potentials in denervated muscle. J Physiol 1975;244(2):313–323.[Abstract/Free Full Text]
  2. Bryan WW, Reisch JS, McDonald G, Herbelin LL, Barohn RJ, Fleckenstein JL. Magnetic resonance imaging of muscle in amyotrophic lateral sclerosis. Neurology 1998;51(1):110–113.[Abstract/Free Full Text]
  3. Kikuchi Y, Nakamura T, Takayama S, Horiuchi Y, Toyama Y. MR imaging in the diagnosis of denervated and reinnervated skeletal muscles: experimental study in rats. Radiology 2003;229(3):861–867.[Abstract/Free Full Text]
  4. Bendszus M, Koltzenburg M. Visualization of denervated muscle by gadolinium-enhanced MRI. Neurology 2001;57(9):1709–1711.[Abstract/Free Full Text]
  5. May DA, Disler DG, Jones EA, Balkissoon AA, Manaster BJ. Abnormal signal intensity in skeletal muscle at MR imaging: patterns, pearls, and pitfalls. RadioGraphics 2000;20(Spec Issue):S295–S315.[Abstract/Free Full Text]
  6. Grant GA, Britz GW, Goodkin R, Jarvik JG, Maravilla K, Kliot M. The utility of magnetic resonance imaging in evaluating peripheral nerve disorders. Muscle Nerve 2002;25(3):314–331.[CrossRef][Medline]
  7. Polak JF, Jolesz FA, Adams DF. Magnetic resonance imaging of skeletal muscle: prolongation of T1 and T2 subsequent to denervation. Invest Radiol 1988;23(5):365–369.[Medline]
  8. Sano S, Nagano T, Imai T, Gotoh M, Kojima T, Nishijima H. An experimental study on entrapment neuropathy by sciatic nerve compression in the rat. J Jpn Soc Surg Hand 1985;2:565–568.
  9. Bridge PM, Ball DJ, Mackinnon SE, et al. Nerve crush injuries: a model for axonotmesis. Exp Neurol 1994;127(2):284–290.[CrossRef][Medline]
  10. Mulkern RV, Wong ST, Jakab P, Bleier AR, Sandor T, Jolesz FA. CPMG imaging sequences for high field in vivo transverse relaxation studies. Magn Reson Med 1990;16(1):67–79.[Medline]
  11. George LT, Myckatyn TM, Jensen JN, Hunter DA, Mackinnon SE. Functional recovery and histomorphometric assessment following tibial nerve injury in the mouse. J Reconstr Microsurg 2003;19(1):41–48.[CrossRef][Medline]
  12. Shabas D, Gerard G, Rossi D. Magnetic resonance imaging examination of denervated muscle. Comput Radiol 1987;11(1):9–13.[CrossRef][Medline]
  13. Fleckenstein JL, Watumull D, Conner KE, et al. Denervated human skeletal muscle: MR imaging evaluation. Radiology 1993;187(1):213–218.[Abstract/Free Full Text]
  14. Uetani M, Hayashi K, Matsunaga N, Imamura K, Ito N. Denervated skeletal muscle: MR imaging—work in progress. Radiology 1993;189(2):511–515.[Abstract/Free Full Text]
  15. West GA, Haynor DR, Goodkin R, et al. Magnetic resonance imaging signal changes in denervated muscles after peripheral nerve injury. Neurosurgery 1994;35(6):1077–1086.[Medline]
  16. Henkelman RM, Stanisz GJ, Kim JK, Bronskill MJ. Anisotropy of NMR properties of tissues. Magn Reson Med 1994;32(5):592–601.[Medline]
  17. Pierpaoli C, Basser PJ. Toward a quantitative assessment of diffusion anisotropy. Magn Reson Med 1996;36(6):893–906.[Medline]
  18. Basser PJ, Mattiello J, LeBihan D. MR diffusion tensor spectroscopy and imaging. Biophys J 1994;66(1):259–267.[Medline]
  19. Hajnal JV, Doran M, Hall AS, et al. MR imaging of anisotropically restricted diffusion of water in the nervous system: technical, anatomic and pathologic considerations. J Comput Assist Tomogr 1991;15(1):1–18.[Medline]
  20. Pierpaoli C, Jezzard P, Basser PJ, Barnett A, Di Chigro G. Diffusion tensor imaging of the human brain. Radiology 1996;201(3):637–648.[Abstract/Free Full Text]

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