The aim of this study was to investigate the feasibility of functional magnetic resonance imaging [blood oxygen level-dependent (BOLD) imaging and T2-Mapping] to monitor the activation of lumbar paraspinal muscles before and after exercise. The ethics committee of the local hospital (the First Affiliated Hospital of Kunming Medical University) approved the study. BOLD and T2-Mapping of paraspinal muscles was performed in 50 healthy young volunteers prior to- and after upper-body extension exercises. The designed movement tasks included upper body flexion and extension movements using a simple Rome chair. Cross-sectional area (CSA), R2*, and T2 values were measured in various lower-back anatomical regions. SPSS22.0 statistical software was used to analyze and compare all the data. BOLD and T2-Mapping are feasible non-invasive and indirect assessments of muscle activation in lumbar paraspinal muscles before and after exercise.
Keywords: BOLD; CSA; fMRI; muscle activation; paraspinal muscle; T2-Mapping
The lumbar paraspinal muscles are involved in motor function and stability of the lower back. Lower-back pain (LBP) is a common clinical problem that can impact quality of life. LBP is caused by the chronic aseptic inflammation of lumbar muscles, muscle degeneration, and lumbar disk protrusion, amongst other causes [1-2]. Early rehabilitation training is the primary treatment for patients with LBP in a clinical setting . Currently, magnetic resonance imaging (MRI) or computed tomography (CT) based cross-sectional area (CSA) of the lumbar paraspinal muscles is used for the assessment of the curative effects of rehabilitation training in LBP [4-7]. However, Motosuneya & Parkkola [7-8] revealed that obvious atrophy of the lumbar paraspinal muscles can occur without a reduction in the total CSA. The atrophied paraspinal muscle tissue may be replaced by fat and fibrous tissue with an insignificant change in total CSA, leading to reduced muscle activation. Microcirculatory blood perfusion (MBP), water metabolism and energy metabolism may also be affected. CSA only detects morphological changes of the paraspinal muscles, but both compositional and functional changes can occur in LBP . Thus, the total CSA of paraspinal muscles is not a suitable marker to evaluate muscle activation.
Blood oxygen level–dependent (BOLD) MRI is a commonly used to assess neuronal activation [10-11]. Since BOLD is based on the principle that the transverse relaxation rate R2* (1/T2*) depends on the ratio of deoxyhemoglobin to oxyhemoglobin in the blood surrounding muscle tissue [10-13], it may be used to assess the peripheral microcirculation in skeletal muscle tissue. T2-Mapping by contrast, is a measure of tissue transverse relaxation time, which can be used as a quantitative index of tissue compositional changes, water metabolism, lactic acid metabolism, fat degeneration, and other indirect biochemical changes . Muscle BOLD and T2-Mapping have been shown to detect disturbances in MBP and biochemical metabolism in some diseases including peripheral arterial occlusive disease, Duchenne muscular dystrophy, cartilage imaging, and ischemic heart disease [15-18]. Whether BOLD/T2-mapping is superior to CSA when evaluating muscle activation after exercise has not been investigated.
The purpose of this preliminary prospective study was to compare the functional MRI (fMRI) parameters (CSA, R2*, and T2 values) of three different paraspinal muscles (iliocostalis, longissimus, and multifidus) between pre-exercise and post-exercise sessions in young healthy volunteers.
Materials and methods
Selection of volunteers
This prospective study was approved by the ethics committee of our local hospital. A total of 50 young healthy volunteers (25 males and 25 females) were recruited from the radiology department of our affiliated hospital (the First Affiliated Hospital of Kunming Medical University). All participants gave written informed consent prior to the study. The average age of the volunteers was 24.81 ± 2.29 years, with an age range of 19–29 years. The clinical baseline characteristics of the study population are shown in Table 1.
All 50 volunteers displayed negative MR lumbar examinations. No subjects showed LBP or clinical signs of lumbar disk herniation. Other exclusion criteria included a history of lumbar surgery, scoliosis, muscle atrophy, professional paraspinal muscle training, and all standard contraindications to MRI examination; including pacemakers, ferromagnetic implants, and claustrophobia.
Design of study and lower-back exercise protocols
All fifty volunteers who were examined with MRI were given 30 mins rest prior to exercise. To exclude subjects with pathological findings such as lumbar disc herniation, general lumbar sagittal T2 weighted imaging and lumbar disc axial T1 weighted imaging were performed prior to exercise. Following initial BOLD and T2-mapping in the resting state, lower-back exercises were performed for 10 mins outside the scanner room. Lower-back hyperextensions using a 45-degree Roman chair for support were performed, which is an isotonic upper-body extension exercise that works the lower back, specifically the erector spinae muscles. Volunteers could adjust the upper Roman chair pad height, leaving enough room to bend at the waist without restriction. The steps included in the exercises were as follows: (1) hands were crossed behind the head and the body was kept straight; (2) the subject began to slowly bend forward at the waist as far as possible, whilst keeping the back flat; (3) the subject slowly raised their torso back to the original position. Subjects were requested to repeat the combined movements 15 times as one set of actions. The entire task consisted of three sets of actions, with a 30-s interval between the two actions (Fig. 1, 2). After completing all actions, BOLD and T2-Mapping were repeated using identical scanning protocols to those used in the resting state.
Magnetic resonance imaging
MRI scans were performed on a 3.0T whole-body MR scanner (Achieva 3.0T Tx, Philips Healthcare, Best, The Netherlands) using a dedicated sensitivity encoding body coil (Philips Healthcare). Volunteers were requested to compress the abdomen with an abdominal bandage during MR examination to reduce respiratory motion artifacts. Volunteers were placed in a standard prone position, and a wedge-shaped foam pad was placed under the lower limbs. Hands were placed on the chest to avoid potential aliasing artifacts (Fig. 1c).
MRI scans of the lower back were performed twice for each volunteer. The first examination protocol involved sagittal T2-weighted images of lumber spines, axial T1-weighted images of intervertebral disks, and muscle BOLD and T2-Mapping (Fig. 3a, 3b). BOLD multi-echoes fast field echo (mFFE) and T2-Mapping images were acquired in the transverse orientation, and slice positions were aligned perpendicularly to the upper edge of L3–L4 levels of volunteers using sagittal T2-weighted images (Fig. 3c-3f). Muscle BOLD acquisition parameters were as follows: field of view (FOV) = 100 × 218 × 72 mm3; repetition time (TR) = 466 ms; number of excitation (NEX) = 6; Voxel = 1.5 × 1.5 × 4 mm3; slice thickness = 3.0 mm; and slice increment = 0.0 mm. Six echo images with nearly identical increasing echo times (TE) were acquired: TE = 3.7, 10.3, 15.9, 21.5, 27.1, 32.7 ms. T2-mapping was based on a fast spin-echo sequence: FOV = 100 × 211 × 79 mm3; TR = 1974 ms; NEX = 1; Voxel = 0.76 × 0.76 × 0.3 mm3; slice thickness = 3.0 mm; slice increment = 0.7 mm; and TE = 7, 13, 19, 25, 31, and 37 ms (Table 2).
Data measurement and analysis
All image series (twice BOLD images and twice T2-Mapping images before and after exercise) were analysed independently on a commercially available workstation (Advantage Windows 4.4, GE Medical Systems, USA) by two radiologists with 5 years’ experience of MRI and the musculoskeletal system. Exercise time and all personal details (i.e., name, age, and sex) were removed from the images to ensure radiologists were blinded to the patient information and examination time. Muscle CSA, R2*, and T2 values of the bilateral lower-back muscles were obtained on a region of interest (ROI) basis. The radiologists delineated the shape of the muscles manually, which included bilateral iliocostalis muscles, longissimus muscles, and multifidus muscles on the superior margin of the L3–L4 vertebral body (Fig. 4c-4f). Measurements were performed three times and the average quantitative values calculated to improve accuracy. The ROIs were selected to avoid tendon and muscle fat composition during the measurement process. The post-processing threshold of the R2* images was 71–201; confidence levels were 0.05; and the color range was 20–100. The post-processing threshold of T2-Mapping images was 10; confidence levels were 0.05; and the color range was 33–71. The DCSA, DR2*, and DT2 of the muscles were calculated according to the following equation:
DCSA = CSApostexercise – CSApre-exercise, DR2*= R2*post-exercise – R2*pre-exercise, DT2 = T2post-exercise – T2 pre-exercise
CSA total= CSAiliocostalis + CSAlongissimus + CSAmultifidus; R2*total = R2*iliocostalis + R2*longissimus + R2*multifidus; T2total = T2iliocostalis + T2longissimus + T2multifidus
All analyses were performed using the statistical software SPSS II for Windows version 22.0 (IBM SPSS Inc., IL, and USA). A P value <0.05 was considered statistically significant. All measured values were expressed as mean ± standard deviation. A paired Student t test was used to compare differences in the CSA, R2*, and T2 of lumbar paraspinal muscles (multifidus, longissimus, and iliocostalis) before and after exercise. The CSA, R2*, and T2 between males and females, left and right sides, and L3 and L4 levels were compared using the independent-samples t-test. A Pearson’s correlation coefficient (r) was used to evaluate the correlation between CSA and R2*, and CSA and T2 values. The following parameters were set to assess the degree of correlation: 0.9</r/<1.0=very high, 0.7 </r/< 0.9= high, 0.5 </r/< 0.7= moderate, 0.3 </r/< 0.5= low, /r/<0.3 = little correlation.
Analysis of CSA, R2*, and T2 before and after exercise
Significant differences were observed in the CSA, R2*, and T2 values of the iliocostalis, longissimus, and multifidus muscles before and after exercise sessions (Tables 3–5 and Fig. 4-6). The CSA of the lower-back muscles on the L3–L4 levels significantly differed between sessions; CSA values on the L3 level were in the following order: iliocostalis > longissimus > multifidus; for the L4 level iliocostalis > multifidus > longissimus. The CSA of the post-exercise session was higher than the pre-exercise session for all lower-back muscles and total muscle area (all P <0.001; Table 3, Fig. 5).
After exercise, the R2* values decreased for all lower-back muscles in both the L3 and L4 levels (all P <0.001; Table 4, Fig. 6); however, these decreases were not significant. The T2 of the paraspinal muscles significantly increased following exercise; the order was multifidus > longissimus = iliocostalis. Similarly, the T2 values following exercise were statistically higher than those of the pre-exercise session (all P <0.001; Table 5, Fig. 7-9).
The differences in pre- and post-exercise CSAs (DCSA) of the iliocostalis were higher than those of multifidus and longissimus (iliocostalis: 84.46 ± 44.05, multifidus: 63.79 ± 50.26, longissimus: 53.89 ± 51.15; Fig. 8) (all P <0.05). However, no significant differences were observed in the DR2* and DT2 values (all P >0.05).
Partial correlation coefficients among the total DCSA, DR2*, and DT2 were obtained by the summation of all values across all muscles). A negative partial correlation coefficient was obtained between the total DCSA and total DR2* (r = 0.3747, P =0.0095; illustrated in Fig. 9). However, partial correlations between total DCSA and DT2 values revealed positive relationships for the paraspinal muscles (r = 0.3445, P =0.0177; illustrated in Fig. 9).
Comparison of CSA, R2*, and T2 with respect to gender, levels, and sides
Comparison of the pre- and post-exercise CSA, R2*, and T2 regarding gender, L3–L4 levels, and left and right sides are shown in Figures 7–9 and demonstrate that changes occurred in the iliocostalis, longissimus, and multifidus muscles after exercise. In all investigated muscles, higher post-exercise CSA and T2 levels and lower post-exercise R2*levels were observed in males and females, L3 and L4 levels, and both left and right sides (P all<0.05). Males displayed larger CSA and lower R2* values on all spinal levels both at-rest and after exercise (all P <0.001) (Figs. 7 and 8). No significant differences between the T2 values of males and females were observed (Fig. 9).
Differences in DCSA, DR2* and DT2 values were evident for the iliocostalis muscles between males and females. Between pre- and post-exercise sessions, the multifidus CSA of the L4 level was larger than that of L3 level (P < 0.05), and longissimus CSA on the L3 level was larger than that the L4 level (P < 0.001). Similar to gender and L3–L4 levels, significant differences were observed in the CSA, R2*, and T2 of both left and right muscles following exercise (P < 0.05). However, no significant difference between the left and right muscles of all quantitative parameters, pre- and post-exercise were observed (P > 0.05) (Figs. 7–9).
This study examined exercise-induced changes in muscle tissue and activation following equal exercise intensities in different lower-back muscles. Analysis was performed using T2-weighted MRI data based CSAs. Using this approach, we obtained new insights on the activation of lower-back muscles after exercise, through exploring the associations between the parameters of muscle MRI (BOLD and T2-Mapping) and traditional CSA. To avoid any undesirable effects of exercise-related movements on non-paraspinal muscles, lower back hyperextensions were performed using a 45-degree Roman chair to evoke muscle activation. MRI data were acquired in the supine position before and after the exercise.
BOLD imaging has been used to assess neuronal activity, but the activation paradigm of muscles differs from that of brain tissue. A complex cognitive test on any motor or sensory task leads to brain tissue activation. However, drugs, exercise, and oxygen were used to accomplish muscle activation . In addition, dynamic changes in muscle MBP, blood flow, and biological metabolism are difficult to understand as real-time spatial and temporal data are difficult to obtain in moving muscle. Changes in BOLD and T2-Mapping of muscle following exercise in this study provided insight into the changes of muscle activation, but R2* and T2 values can be affected by numerous biological factors in human muscle.
MBP is an important indicator of the muscle microcirculatory reserve capacity, which is important in the assessment of muscle activation of an athlete. Muscle microcirculatory reserve capacity is defined as the difference between the MBP when muscle is in the maximum diastolic state (when the muscle temperature reaches 44°C) to when the muscle is resting . Laser Doppler flowmeter is a relatively accurate method to assess muscle MBP, but its application is confined to skin and shallow muscle tissue. BOLD is primarily dependent on the deoxyhemoglobin content, a paramagnetic substance that allows BOLD to indirectly measure the oxygenation status and MBP of a tissue, through the detection of R2* changes [10, 13]. Compared to laser Doppler flowmeter, BOLD allows the assessment of biological metabolic changes in deep muscle tissue, and also allows accurate anatomical mapping when superimposed onto high-resolution anatomical MRI , a technique also employed in brain, myocardial ischemia, liver cancer, and skeletal muscle studies [10,15,17,22,23].
In this study with healthy volunteers, following regional paraspinal muscle stimulation via lower back hyperextensions, several types of signal changes were observed. All groups (males/females, L3/L4 levels, right/left sides) displayed higher CSA and T2 values and lower R2* values in all lower-back muscles following exercise. However, no significant differences were found for the DR2* and DT2 values between L3 and L4 levels or right and left sides.
Activity-related changes in T2-mapping reflect increased T2 relaxation times of skeletal muscle . In addition, T2-mapping can be used as a quantitative metric for the evaluation of various muscle functions. Hiepe et al. reported that the increase in T2 following spinal muscle movements was related to changes in muscle metabolism [25-26], the number of capillaries, and the degree of fat infiltration in the muscle.
Following skeletal muscle exercise, osmotic pressure in the muscle cells increases due to increased levels of muscle cell metabolites (for example lactic acid), resulting in increased water content in the extracellular space. Moreover, the increase in muscle T2 was related to the degree of muscle stimulation and contraction. Mayer showed that T2 values are higher in spinal muscle during increased exercise intensity . In this study, the increased T2 of the upper margin of L3-L4 following exercise may be related to the presence of lactic acid and water following muscle activation. This may also explain the increase in muscle CSA we observed.
The correlation between total DCSA and total DR2* or total DT2 indicated a low-negative and positive-correlation, respectively. This could be explained by the fact that each quantity was influenced by differing and complex biological information. CSA reflects the overall change in muscle morphology after exercise; R2* and T2 values can be affected by muscle microcirculatory blood perfusion, blood volume, extracellular water content and other biological factors. The specific effects of these different factors warrant further investigation.
The present study had some limitations. Firstly, the number of participants was limited which may impact the observations. Secondly, BOLD and T2-mapping cannot be accomplished simultaneously following paraspinal muscle exercise, meaning there was a lag time between measurements. Thirdly, only young healthy volunteers with an age range of 19-29 years were enrolled. Thus, our data may not extend to other subject groups.
In conclusion, BOLD and T2-mapping provides useful functional information over that available from morphological imaging alone. These techniques may be used to evaluate muscle activation of paraspinal muscles and can provide deeper insights into muscle physiology, in addition to the use of CSA.
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