Shear wave elastography in the diagnosis of rhabdomyolysis

Abstract

Rhabdomyolysis is a life-threatening skeletal muscle disease, the time of diagnosis and initiation of treatment of which directly affects the likelihood of developing acute kidney injury and the quality of recovery of muscle function. The ultrasound method of diagnostics is accessible and can be used at the stage of primary diagnosis, but it has low sensitivity of 68% and specificity of 57% when using such ultrasound symptoms as a diffuse expressed increase of echogenicity (homogeneous or heterogeneous), disorder of transverse striation of the muscle structure and high volume of the muscular tissue damage (over 30%).

The possibility of ultrasonic elastography in the diagnosis of rhabdomyolysis in 95 patients admitted with suspected damage to muscle tissue are discussed. Comparison of the parameters of shear wave elastography in patients with rhabdomyolysis and patients with other diseases manifested by muscle edema (muscle contusion, inflammatory myopathies, post-exercise muscle edema), as well as with the control group, significant differences were noted (p < 0.01) allows to determine the quantitative ultrasound characteristics of muscle tissue, pathognomonic for rhabdomyolysis. The use of shear wave elastography with obtaining lateral wave velocity of less than 1.64 m/s increased the sensitivity and specificity of the method in the diagnosis of rhabdomyolysis to 75 and 62%, respectively.

A logit model with integrated use of elastography indices was developed, with a diagnostic accuracy of 77%. During muscle recovery, there was an increase in lateral wave velocity to the level of control group values, which can be used as one of the markers of patient recovery.

Full Text

INTRODUCTION

Rhabdomyolysis is a disease characterized by the destruction of skeletal muscles, leading to the release of intracellular contents into the blood, which can cause life-threatening complications. Although most patients with rhabdomyolysis have a favorable prognosis, acute kidney injury develops in 7–10% of cases [1]. Studies by some authors have confirmed that early diagnosis and timely adequate treatment can not only prevent the occurrence of complications of rhabdomyolysis, but also significantly improve the prognosis of patients [2, 3].

In the presence of the classic triad of rhabdomyolysis symptoms, such as myalgia, muscle weakness and brown urine, the diagnosis set quickly and accurately. However, a similar clinical picture is observed in less than 10% of patients at the initial visit. The main complaints in most cases are local or widespread muscle pain and feeling unwell [4]. Thus, the absence of a specific clinical picture in some situations can lead to an underestimation of the severity of the patient and the late appointment of laboratory tests for specific markers of acute muscle damage: creatinephosphokinase (CPK) and blood myoglobin [5].

A number of works list various signs of rhabdomyolysis during ultrasound examinations, such as muscle thickening, changes in echogenicity, the appearance of ground glass, and others [6, 7]. In this case, ultrasound is usually used only to confirm the diagnosis after laboratory data [8]. However, a number of authors present cases where it was ultrasound examination that made it possible to suspect acute damage to skeletal muscles with an erased clinical picture and to conduct a blood test of patients for CPK [9, 10].

The ultrasound picture in rhabdomyolysis can be varied and not differ from other diseases manifested by edema muscle tissue: traumatic injuries, inflammatory myopathies, injuries associated with excessive physical activity and others. Some articles point to the low specificity of ultrasound in detecting muscle edema [7, 11, 12].

An increase in diagnostic characteristics is possible using a quantitative ultrasound technique - shear wave imaging (SWI). Elastography has shown to be effective in examining many organs, such as the liver, mammary glands, blood vessels, and the prostate gland [13, 14]. SWI is used to diagnose diseases of the organs of the musculoskeletal system, for example, tendons [15], some hereditary myopathies [16, 17]. There are isolated works on the use of SWI in skeletal muscle lesions [15, 18, 19].

The aim of the study was to improve the diagnostic efficiency of ultrasound in detecting rhabdomyolysis using quantitative elastography.

MATERIALS AND METHODS

All patients were examined after signing a voluntary informed consent. A total of 95 patients were examined. An ultrasound examination was performed at the stage of primary diagnosis with a clinical picture of skeletal muscle diseases: complaints of myalgia, swelling of the extremities, decreased muscle strength.

The patients were divided into two groups. The main group (n=54) included cases with proven acute damage to muscle tissue (increased levels of CPK and blood myoglobin, the presence of changes in the images of radiation diagnostic methods). The rest of the patients were included in the control group. In the main group, two subgroups were distinguished: cases of confirmed rhabdomyolysis (n=18) and other diseases accompanied by muscle edema (muscle bruises, inflammatory myopathies, delayed muscle pain syndrome, post-exercise edema). Verification of rhabdomyolysis was carried out on the basis of the detection of myoglobinemia more than 72 ng/ml.

Patients were examined on an ultrasound diagnostic expert class Logiq E9 scanner (General Electric, USA). A linear high-frequency transducer for superficial tissues was used. Patient preparation was not required. Scanning was performed in a two-dimensional mode in the area of ​​damage and adjacent, as well as opposite areas.

A gel pad was used to eliminate the effect of sensor compression on muscle tissue. SWI was performed with the patient lying on his back in a state of relaxation of all skeletal muscles. For visual assessment, a color scale was used, where dark blue color meant the minimum elasticity, and red color - the maximum. Areas of interest were identified in the middle sections of the muscles without the involvement of tendons and muscle sheaths. To obtain more accurate results, the measurement was carried out at several levels with the calculation of the average value. ESW parameters were expressed as side wave velocity (V) in m/s and stiffness values ​​(Young's modulus, E) in kPa.

Statistical processing of experimental data was carried out using MedCalc software (version 18.2.1). The normality of distribution was determined using the D'Agostino-Pearson test. The quantitative results of morphometric analysis were expressed as “Me [1st quartile; 3rd quartile]". The Mann-Whitney U-test was used to compare groups of SWI values. To determine the cut-off thresholds for side wave velocity and stiffness, ROC analysis and comparison of AUC using the DeLong method were carried out. The complex use of quantitative characteristics was carried out using the construction of a binary logistic regression equation.

RESULTS

Ultrasound signs of rhabdomyolysis included a diffuse pronounced increase in echogenicity (homogeneous or heterogeneous), a violation of the transverse striation of the muscle structure, and a large amount of muscle tissue damage (more than 30%) (Fig. 1). The conclusion "rhabdomyolysis" was made in cases of detection of all the listed ultrasound symptoms.

Fig. 1. Echograms of rhabdomyolysis of skeletal muscles of various anatomical regions: a - back extensor muscle, b - medial and lateral heads of the triceps brachii muscle 

Twenty-seven cases met the ultrasound criteria for rhabdomyolysis. After laboratory verification of rhabdomyolysis, the following diagnostic efficiency of ultrasound was determined: sensitivity - 68%, specificity - 57%, accuracy - 62%. At the same time, despite the low sensitivity of the method in the diagnosis of rhabdomyolysis, the sensitivity of ultrasound in detecting nonspecific edematous changes in muscle tissue (patients of the main group) was 74%.

Thus, ultrasound examination makes it possible to detect muscle edema, however, the absence of ultrasound signs and a subjective assessment of the echogenicity of the muscle structure leads to a large number of type I and II errors. To increase the effectiveness of the ultrasound method in the diagnosis of rhabdomyolysis, a quantitative assessment of the elasticity of muscle tissue was carried out.

When comparing the stiffness coefficients of muscle tissue in m/s and in kPa, it was found that the values ​​for rhabdomyolysis are statistically significantly different from other diseases manifested by muscle edema (U- the Mann-Whitney test with Bonferroni correction, p < 0.0001), and from the control group (Mann-Whitney U-test with Bonferroni correction, p < 0.0001) downwards (Fig. 2). At the same time, the lateral wave velocity and stiffness in muscle edema did not statistically significantly differ from the control group: p = 0.5833 and p = 0.1168, respectively (Mann-Whitney U-test with Bonferroni correction).

Fig. 2. Echograms with the measurement of the SWI parameter, the upper row - with rhabdomyolysis, the lower row - in the control group: a - back extensor muscles, b - wide external thigh muscle, c - pectoralis major muscles 

Thus, it can be concluded that SWI allows the diagnosis of rhabdomyolysis, but does not allow differentiation of other forms of muscle edema from normal muscle.

Cut-off thresholds for ESV for rhabdomyolysis were determined using ROC analysis based on the Youden criterion (Fig. 3). When comparing the AUC of the obtained curves, no significant differences were found (DeLong method, p = 0.9761).

Fig. 3. Diagrams of ROC-analysis of SWI data separately and comparative analysis of ROC-curves. The dots indicate the optimal values ​​of the cut-off thresholds determined by the Youden criterion

The dots indicate the optimal values ​​of the cutoff thresholds determined by the Youden criterion For stiffness, a value of E = 6.38 kPa was obtained with a sensitivity of 51%, a specificity of 92%, and an accuracy of 70%. Evaluation of SWI means separately allowed to improve the efficiency of ultrasound diagnosis of rhabdomyolysis compared to the native study, however, this increase was insignificant.

For the complex use of SWI means, a binary logistic regression model was built. The method of sequential introduction of variables into the model was used with the coefficients checked for significance (p < 0.05) at each stage.

The resulting SWI model shows a satisfactory coefficient of determination (Nagelkerke R2 = 0.38). The formula of the final model is presented below:

P+ =1/(1+e^(-(-0.22391*E-1.45259*V+3.87874))),

where P+ is the probability of rhabdomyolysis (P+ > 0,5 - positive probability);

e - base of the natural logarithm;

E - elastographic stiffness, expressed in kPa;

V - side wave velocity, expressed in m / s.

The SWI model made it possible to classify cases of rhabdomyolysis with a diagnostic accuracy of 77%. In the ROC analysis of the predicted values ​​at the optimal point, the sensitivity and specificity were 84% and 65%, respectively.

When evaluating the data in the control group, an abnormal distribution of SWI means was noted. medians values ​​and interquartile range for side wave velocity were V = 2.03 [1.72; 2.64] m/s, for stiffness E = 13.22 [10.09; 22.41] kPa.

In five cases, the muscle tissue of patients with rhabdomyolysis was assessed before discharge. At the same time, the means of the velocity of the lateral wave of damaged muscles in all patients after recovery were included in the interquartile range of the values ​​of the control group.

DISCUSSION

Ultrasound is highly accessible in the diagnosis of muscle tissue diseases both during the initial examination and in the dynamics of the disease. With regard to rhabdomyolysis, the speed and accuracy of diagnosis are critical to the prognosis and recovery of the patient [3]. Despite the relatively low diagnostic capabilities, even a native ultrasound study provides information about the state of muscle tissue, and knowledge of the semiotics of rhabdomyolysis makes it possible to suspect acute damage to skeletal muscles and prescribe specific laboratory tests to confirm or exclude it [8].

The study demonstrated that the capabilities of native ultrasound in the detection of rhabdomyolysis is insufficient, but the method can detect undifferentiated muscle edema with a sensitivity of 74%. At the same time, it is worth noting the advantages of the method: a short examination time, the ability to perform in patients in serious condition without transportation to other rooms and the absence of exposure to ionizing radiation. In addition to the primary diagnosis, ultrasound made it possible to monitor the state of muscle tissue in patients for the entire period of stay in the intensive care unit.

SWI, expressed in the speed of the lateral wave, made it possible to improve the main diagnostic characteristics of ultrasound in the detection of rhabdomyolysis, first of all, sensitivity. A decrease in the speed of the lateral wave in muscle edema is noted in the work on the diagnosis of inflammatory myopathies [20] and the description of a clinical case of rhabdomyolysis [18]. The decrease in elastographic stiffness is explained by an increase in the volume of extracellular and intracellular water during tissue edema, which leads to a decrease in the propagation velocity of the lateral wave from the central ultrasound ray.

SWI, expressed in stiffness, in the diagnosis of rhabdomyolysis showed an extremely low sensitivity value of 51%, which does not allow the use of this technique. With an empirical selection of the cut-off threshold with a balance between sensitivity and specificity, the results obtained did not differ from the capabilities of a qualitative method. This is explained by the fact that the Young's modulus is calculated from the speed of the side wave and, therefore, is less accurate than the initially measured value [13]. However, the specificity and accuracy of stiffness were higher than that of the side wave velocity.

The combined use of side wave velocity and stiffness using a logistic regression model made it possible to compensate for the heterogeneity of the distribution of sensitivity and specificity of SWI means separately and form a formula for determining the probability of rhabdomyolysis with a fairly high accuracy of 77%.

The SWI method, expressed as lateral wave velocity, has been able to assess muscle tissue recovery during recovery, which is consistent with the scientific studies of Botar-Jid C. et al. [21] and Alfuraih A.M. et al. [20], which show an increase in SWI values ​​up to standard values ​​in some edematous and inflammatory lesions with positive dynamics of the course of diseases.

CONCLUSION

Thus, the developed logit model with the complex use of elastography values ​​allows increasing the diagnostic accuracy of ultrasound in determining rhabdomyolysis from 62% to 77%. Increasing the speed of the side wave to the standard values ​​V = 2.03 [1.72; 2.64] m/s indicates the restoration of muscle tissue after the disease.

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About the authors

Aleksandr A. Emelyantsev

Military Medical Academy

Author for correspondence.
Email: yemelyantsev@gmail.com
ORCID iD: 0000-0001-5723-7058
SPIN-code: 6895-7818
Scopus Author ID: 57223387651

M.D., Ph.D. (Medicine), Senior Lecturer of the Radiology and Radiology Department with a course of ultrasound diagnostics

Russian Federation, 6, Akademika Lebedeva str., Saint Petersburg, 194044

Sergey N. Bardakov

Military Medical Academy

Email: epistaxis@mail.ru
ORCID iD: 0000-0002-3804-6245
SPIN-code: 2351-4096
Scopus Author ID: 57193732211

M.D., Ph.D. (Medicine), Lecturer at the Nephrology and Efferent Therapy Department

Russian Federation, Saint Petersburg

Igor’ V. Boikov

Military Medical Academy

Email: qwertycooolt@mail.ru
SPIN-code: 1453-8437

M.D., D.Sc. (Medicine), Professor, Deputy Head of the Radiology and Radiology Department with a Course in Ultrasound Diagnostics

Russian Federation, Saint Petersburg

Vladimir N. Malakhovskiy

Military Medical Academy

Email: malakhovskyvova@gmail.com
SPIN-code: 2014-6335

M.D., D.Sc. (Medicine), Professor, Lecturer at the Radiology and Radiology Department with a course in ultrasound diagnostics

Russian Federation, Saint Petersburg

Tamara E. Rameshvili

Military Medical Academy

Email: rentgenvma@mail.ru
SPIN-code: 3034-3209

M.D., D.Sc. (Medicine), Professor, Senior Lecturer of the Radiology and Radiology Department with a course of ultrasound diagnostics

Russian Federation, Saint Petersburg

Vadim A. Tsargush

Military Medical Academy

Email: tsargushvmf@mail.ru
ORCID iD: 0000-0002-5459-986X
SPIN-code: 2599-1515
Scopus Author ID: 57214886746

M.D., Ph.D. (Medicine), radiologist

Russian Federation, Saint Petersburg

Gennadiy G. Romanov

Military Medical Academy

Email: romanov_gennadiy@mail.ru
ORCID iD: 0000-0001-5987-8158
SPIN-code: 9298-4494
Scopus Author ID: 56024998000

M.D., Ph.D. (Medicine), Associate Professor of the Radiology and Radiology Department with a course of ultrasound diagnostics

Russian Federation, Saint Petersburg

Anna A. Bagrova

Military Medical Academy

Email: annieba@mail.ru
SPIN-code: 6969-7667

the Head of the medical department

Russian Federation, Saint Petersburg

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Copyright (c) 2022 Emelyantsev A.A., Bardakov S.N., Boikov I.V., Malakhovskiy V.N., Rameshvili T.E., Tsargush V.A., Romanov G.G., Bagrova A.A.

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