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Significance of Diffusion Tensor Imaging of Vastus Medialis Oblique in Recurrent Patellar Dislocation

Background: Numerous studies have investigated the influence of osseous factors on patellofemoral joint instability, but research on the influence of dynamic muscle factors in vivo is still in the exploratory stage. This study aimed to use magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to evaluate vastus medialis oblique (VMO) fiber bundles in patients with recurrent patellar dislocation to explore the changes in muscle morphology and function. Methods: This prospective study involved 30 patients (7 males and 23 females; average age, 21.4 ± 3.8 years) clinically diagnosed with recurrent patellar dislocation in Peking University Third Hospital and 30 healthy volunteers matched for age, sex, and body mass index in our medical school between January 2014 and October 2014. None of the patients had a recent history of traumatic patellar dislocation or transient patellar dislocation. All patients underwent conventional MRI and DTI of the knee. The cross-sectional area of the VMO on MRI and the fractional anisotropy (FA), apparent diffusion coefficient (ADC), and primary (λ1), secondary (λ2), and three-level characteristic (λ3) values on DTI were measured. The independent-samples t-test was used to compare these parameters between the two groups. Results: Compared with the control group, the patient group showed significantly higher FA values (0.39 ± 0.05 vs. 0.33 ± 0.03) and significantly lower ADC (1.51 ± 0.13 vs. 1.58 ± 0.07), λ2 (4.96 ± 0.13 vs. 5.04 ± 0.07), and λ3 values (4.44 ± 0.14 vs. 4.58 ± 0.07; t = 5.99, t = –2.58, t = –3.02, and t = –4.88, respectively; all P < 0.05). Cross-sectional VMO area and λ1 values did not differ between the two groups (t = –1.82 and t = 0.22, respectively; both P > 0.05). Conclusions: The functional status of the VMO is closely associated with recurrent patellar dislocation. MRI, especially DTI (FA, ADC, λ2, and λ3), can detect early changes in VMO function and might facilitate the noninvasive monitoring of the functional status of the VMO in patients with recurrent patellar dislocation.


Subjects
This prospective study was conducted on patients with recurrent patellar dislocation that was clinically diagnosed in Peking University Third Hospital between January 2014 and October 2014. The study protocol was approved by the Ethics Committee at our institution (Peking University Third Hospital) (No. 2014165) and written informed consent was obtained from each patient. Patients were eligible for inclusion in this study if they met the following criteria: multiple episodes of patellar dislocation (more than twice); no knee joint fracture, ligamentous injury, or rupture; no history of knee joint trauma within the past month; and nonathletes without a history of strenuous exercise of the lower extremities within the past month.
Healthy controls were recruited from volunteers in our medical school who had no history of knee-joint trauma, operation, or pain. The controls' history, age, height, and weight were recorded, and the individuals were included in the study if their age, sex, and body mass index (BMI) could be matched with those of the patients. All matched healthy volunteers were nonathletes who had no history of strenuous exercise of the lower extremities during the past month. Informed consent was obtained from both patients and controls.

Imaging method
All patients underwent scanning of the knee joint from the superior border of the patella to the tibial tubercle in a supine position with the knee extended. All scans were obtained using a 3.0-T superconductive MRI Scanner (Signa HDxt, GE Medical Systems, LLC, Milwaukee, WI, USA). A special eight-channel knee-joint coil was used during the scanning. The scanning sequences have been listed below.

Evaluation of imaging data
All images were transmitted to a PACS System (Centricity RIS CE 3.0, GE Medical Systems) on an image workstation (Centricity Radiology RA 600, GE Medical Systems). The PACS system was used to measure the cross-section of the VMO on the FSE PDWI scans of the knee joint. The FuncTool software (GE Medical Systems) was used for the postprocessing of DTI data. We evaluated multiple cross-sectional images of the VMO, starting from the superior border of the patella and moving downward until the muscle fiber bundle disappeared (generally 5 or 6 levels). We delineated the region of interest (i.e., the VMO) on every cross-section. We also measured the fractional anisotropy (FA), apparent diffusion coefficient (ADC), and primary (λ1), secondary (λ2), and three-level characteristic values (λ3) of the VMO on each image. The measurement accuracy was to two decimal places. The average values of the measurements taken for different cross-sections were used in the final analysis. All measurements were repeated after an interval of 3 months, by the same researcher.
Statistical analysis SPSS 19.0 software (SPSS, IBM, NY, USA) was used for statistical analysis. All measurement data were expressed as mean ± standard deviation (SD). The independent-samples t-test was used for comparisons between the two groups.

General information
We enrolled 30 patients and 30 matched controls in this study. All patients underwent routine MRI and DTI of the knee joint. The patient group consisted of 7 males (3 left knees, 4 right knees) and 23 females (11 left knees, 12 right knees). The average age of the patients was 21.4 ± 3.8 years (range, 15-29 years), and their average BMI was 21.2 ± 3.2 kg/m 2 . The control group also included 7 males (3 left knees, 4 right knees) and 23 females (11 left knees, 12 right knees). The average age of the controls was 21.9 ± 3.1 years (range, 15-29 years), and their average BMI was 20.8 ± 2.6 kg/m 2 . There were no statistically significant differences in age and BMI between the two groups (t = -0.64 and t = 0.50, respectively; both P > 0.05).

Cross-sectional area of the vastus medialis oblique
The average cross-sectional area of the VMO was 3.79 ± 1.03 cm 2 in the patient group and 4.41 ± 1.57 cm 2 in the control group. No significant difference was present in this area between the two groups (t = −1.82, P = 0.07).
dynamic soft-tissue forces that interact in a complex way. Ligamentous and bony anatomy of the knee is the primary stabilizer, and the quadriceps musculature is the secondary stabilizer. The influence of dynamic soft-tissue constraints on the stability at the patellofemoral joint remains controversial. [4] The vastus medialis muscle can be divided into a long head and the VMO. The VMO originates from the medial part of the distal end of the femur and adductor tubercle and attaches to the medial patellar retinaculum and superomedial border of the patella. The VMO is considered to be the main dynamic patellar-stability device against the acting force of the vastus lateralis muscle. Dysfunction of the VMO can reduce the binding force of the medial patella and forms part of the pathological basis of recurrent lateral patellar dislocation. [5][6][7] However, due to the complex etiology of patellar dislocation, with abnormal bony structure considered as the main responsible factor, it is unclear whether or not structural and functional abnormalities of the VMO are causally linked to recurrent patellar dislocation. [8][9][10] Skeletal muscle consists of multinucleated fiber cells.
Muscle atrophy leads to the geometric distortion of the cell membrane and decreases the diameter of the muscle fiber, eventually resulting in a reduced muscle cross-sectional area.
In this study, the cross-sectional area of the VMO in patients with recurrent patellar dislocation showed a decreasing trend but was not significantly different from the area in healthy volunteers. It has been speculated that early changes in the muscle fibers are mainly manifested as changes in muscle strength; gross structural abnormalities only occur once the early changes have accumulated to a certain degree. [11] As conventional MRI is unable to quantitatively assess

Diffusion tensor imaging findings
Good consistency was observed between the baseline and 3-month measurements (ICC > 0.9). We, therefore, used the average of the two values for the final analysis. The DTI findings are presented in Table 1. The FA value was significantly higher and the ADC, λ2, and λ3 values were significantly lower among the patients than among the controls [ Figures 1-3]. The λ1 value was higher among the patients than among the controls, but the difference was not statistically significant.

dIscussIon
The present study revealed that the ADC, λ2, and λ3 values of the VMO were significantly lower while the FA value was significantly higher in patients with recurrent patellar dislocation than that in healthy matched controls.

Dynamic factors related to recurrent patellar dislocation
The stability of the patellofemoral joint depends on the underlying morphology and the balance of static and   changes in muscle strength, and as DTI parameters show some correlation with these changes, [12] we speculated that changes in relevant DTI parameters would be more sensitive than changes in the cross-sectional area of VMO.

Sensitivity of diffusion tensor imaging in detecting muscle fiber changes
Since muscle fiber bundles have high anisotropy, the muscle microenvironment can cause changes in the microstructure of muscle fibers, which lead to further changes in DTI parameters; therefore, DTI can have good diagnostic value. [13,14] The FA values of muscles vary with conditions such as edema, muscle damage, and tears; therefore, it is feasible to quantitatively assess the internal micromolecular pathological changes in skeletal muscles by calculating DTI parameters such as FA and ADC values. These values can be used to evaluate skeletal muscle damage, denervation atrophy, ischemia, nutritional disorders, inflammatory lesions, etc., and can sensitively detect changes in the tissue microstructure. [15][16][17] FA values range from 0 to 1. An FA value of 0 represents an absolute isotropic tensor, like a ball, while a value of 1 indicates absolute linear tensors that only spread in one vector direction. ADC values have been associated with cell morphology and mainly reflect diffusion across the cell membrane in the skeletal muscle fibers. The ADC value is decreased when diffusion is limited. The λ1, λ2, and λ3 values represent diffusivity along the long axis of a muscle fiber, along the muscle bundle in the direction of the endomysium, and along the cross-section of the muscle fiber, respectively. [18,19] Okamoto et al. [20] explored the diffusion properties of motion-related changes in calf muscle structure using DTI technology and found changes in ADC, λ1, λ2, and λ3 values among different muscle groups. The authors believed that these changes were caused by cell deformation due to increased intracellular space as well as extracellular components.

Diffusion tensor imaging parameters related to changes in vastus medialis oblique in recurrent patellar dislocation
Muscle relaxation and VMO weakness are congenital factors leading to recurrent patellar dislocation. Human skeletal muscles are mainly divided into two types: Type-1 fibers, which maintain permanent endurance mainly through aerobic metabolism, and Type-2 fibers, which provide maximal mechanical power mainly through anaerobic metabolism. The two types of fibers have different diameters and intracellular microstructures. Type-2 fiber bundles have a larger radius and lower mitochondrial density than Type-1 fiber bundles. Under physiological conditions, the number of muscle fibers in the axial plane and the average diffusivity increase as the muscle contracts; the λ2 and λ3 values decrease as the muscle relaxes. The muscle size and strength gradually decrease with age, mainly due to changes in muscle fiber type and diameter. Type-2 rapid-contraction fibers will begin to atrophy first, leading to decreased muscle fiber diameter and increased extracellular components. [12,18] This study showed that in patients with recurrent patellar dislocation, the ADC, λ2, and λ3 values of the VMO were decreased, while the FA value was increased. The λ2 and λ3 values represent the diffusion tensor perpendicular to the long axis of muscle fiber bundles. Thus, these values are directly proportional to the diffusion direction of the muscle fiber diameter. A decrease in muscle strength may result in the reduction of these two parameters, especially λ3, because it reflects the cross-sectional diffusion tensor of water molecules within individual muscle fibers. [18,19] In addition, the decrease in ADC values observed in this study was mainly attributable to lower λ2 and λ3 values, further illustrating that muscle fibers with a smaller diameter, fewer internal components, and increased extracellular tissue can lead to limited diffusion. Decreased λ2 and λ3 values can result in asymmetric diffusion, reduced radial dispersion coefficient, and higher anisotropy, eventually leading to higher FA values.
Studies have shown that DTI parameters are closely associated with the pathology of muscle lesions and internal tissue structure changes. Scheel et al. [12] reported that FA values are negatively correlated with maximal muscle strength: the weaker is the muscle strength, the greater is the FA value, and the corresponding muscle fiber type also changes. These results are consistent with the findings of the present study. Saotome et al. [21] evaluated mice in which skeletal muscle atrophy was induced by denervation; the authors found that in atrophic muscle tissue, FA values were increased, while λ2 and λ3 values were decreased. This is because λ2 and λ3 reflect the sparse muscle fiber density in the cross-sectional direction, which is caused by a decrease in the diameter of the muscle fibers. The λ1 values were not obviously changed, as λ1 represents the anisotropy of the muscle fibers in the long axis direction. These results are consistent with the findings of the present study. Muscle atrophy is manifested as reduced muscle volume, increased connective tissue, or fat components among muscle bundles on histomorphology, as well as weakened muscle tension. Changes in relevant anisotropy and diffusion function parameters on DTI might be caused by changes in muscle fiber diameter and intracellular diffusion coefficients. In addition, different types of fiber composition, number of water molecules in the intercellular space, and cell membrane permeability also affect DTI parameters. [22,23] The study had two deficiencies. First, the sample size was not large enough. The cross-sectional area of the VMO showed a decreasing trend in patients with recurrent patellar dislocation but without significant differences from healthy volunteers; this result might be different when the sample size is increased. Second, muscle atrophy, in addition to reducing the muscle volume, can also lead to increased connective tissue or fat components among the muscle bundles. Quantitative measurement of the fat components in the intramuscular spaces would have improved the quality of this study and should be pursued in future experiments.
In conclusion, when compared with healthy volunteers, patients with patellofemoral joint instability showed increased FA values and decreased ADC, λ2, and λ3 values in the VMO muscle, implying that a decrease in the diameter of the muscle fibers resulted in decreased muscle strength, which might be a factor causing patellofemoral joint instability. In addition, the cross-sectional area of the VMO showed a decreasing trend, but the difference was not significant. This finding might imply that microstructural changes in the muscle fibers precede morphological changes in the muscles. Thus, relevant DTI parameters can be used to assess the early microstructural changes in skeletal muscles in patients with patellofemoral instability.

Financial support and sponsorship
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Conflicts of interest
There are no conflicts of interest.