Tendinosis is a broad term encompassing pain and disability at the site of tendons associated with the histopathological findings of failed tendon healing response and no classical signs of inflammation. The most common sites of tendinosis involve the rotator cuff tendons (
Several minimally invasive treatments with application of different medication have been introduced, providing good patient outcome.3,4 Platelet rich plasma (PRP) injection therapy is effective in improving symptoms in supraspinatus tendinopathy and lateral epicondylitis.5,6 It is a good treatment option for patients with chronic changes of supraspinatus tendon and lateral epicondylitis who do not meet criteria for surgical management and are not content with the results of conservative treatments.7 Platelet-rich plasma is currently one of the most used and investigated therapeutic options in clinical practice to target symptomatic tendinosis, however its effect was mostly monitored only clinically.8,9 PRP can be delivered directly into the lesion site and, once activated, the platelet concentrate becomes a gel allowing the secretion of the bioactive molecules in situ and stimulates tendon fibrillar remodulation. PRP is an autologous biotechnology that relies on the local delivery of a wide range of growth factors and cytokines with the aim of enhancing tissue healing.10
Gray-scale ultrasound (US) is the most commonly used diagnostic tool to assess tendon pathology, particularly in superficial tendons. It has high level of evidence in shoulder and elbow examination.11 It is easily accessible, noninvasive and it has excellent spatial and contrast tissue resolution. It also enables dynamic assessment of tissues as well as can be used repeatedly without potentially harmful effects to the observed tissues. Additionally, it can also be used to guide and assess different treatments applied to tissues.12 However, US is a qualitative method and is entirely dependent on the performer with high interobserver variability ranging from poor to good.13,14 In order to overcome these limitations and to quantitatively assess tendon structure after specific treatment (
The aim of this study was to quantify short-term effect of PRP therapy in symptomatic supraspinatus and elbow common extensors tendinosis using texture analysis of ultrasound images.
Thirteen patients (7 male and 6 female), age 36–60 years (mean age 51.2 ± 5.2) were initially treated with PRP injection therapy for tendinosis at Institute of Radiology, University Clinical Center Ljubljana from March 2019 till March 2020. Four supraspinatus tendons and nine common extensor tendons of the forearm were treated in this study. The inclusion criteria for patients with supraspinatus tendinopathy was confirmed on MRI and persisting pain with disability for at least 3 months in the shoulder after at least one cycle of physiotherapy. The inclusion criteria for patients with lateral epicondylitis was confirmed by common extensor tendinopathy with US and persisting pain with disability for at least 3 months after at least one cycle of physiotherapy. The exclusion criteria were rheumatoid arthritis, known malignancy, other joint injuries found on imaging, bleeding disorders, pregnancy and use of nonsteroidal anti-inflammatory drugs 7 days before PRP treatment as well as previous invasive treatments of the tendons. Patients were evaluated on the day of the PRP injection therapy and at 3 months follow up. The study was approved by the National Medical Ethics Committee of the Republic of Slovenia (approval number 0120 – 115/2018/4). Written informed consent was obtained from the patients or their authorized representatives in accordance with the Declaration of Helsinki.
Standardized questionnaires were used for the assessment of patient clinical outcome. Patients with lateral epicondylitis completed a Patient-rated tennis elbow evaluation (PRTEE) questionnaire, while patients with supraspinatus tendinopathy completed Shoulder pain and disability index questionnaire (SPADI).17,18 Both questionnaires were translated into Slovenian language and the scale was adjusted so that 0 points was assessed as the best score (
Real-time US examinations of the affected tendons were performed by one of three radiologists subspecialized in musculoskeletal imaging with at least 5 years of experience. US examinations were performed using a 13–15 MHz electronic linear-array transducer on a ProSound F75 scanner (Hitachi Aloka Medical, Ltd. Tokyo, Japan). The imaging resolution was approximately 1 mm in the longitudinal plane, scan width 38 mm and depth of field approximately 50 mm. Six consecutive US images of the tendons were acquired comprising the most affected regions of tendinosis. Probe was placed longitudinally along the course of the tendon fibers with minimal probe movement to acquire the images. At the follow up, the second set of US images were acquired in the same manner. Patient's bony and soft tissue landmarks were used to obtain comparable imaging location, angle and plane.
Platelet-rich plasma preparation was obtained from patient autologous blood. Approximately 30 mL of blood was drawn from patient's non-treated arm and mixed with 1 ml of anticoagulant solution (citrat dextrose). Centrifugation was performed using Harvest SmartPrep 2 (Terumo BCT, USA), which yielded approximately 3 mL of PRP. PRP injection therapy was performed under US guidance into the affected tendon. Patients were in supine position, surgical disinfection was performed and sterile probe sleeve was used. 3 mL of local anesthetic (XylocaineTM) was infiltrated in subacromialsubdeltoid bursae in patients treating supraspinatus tendinosis and in subcutaneous tissue around common extensor tendons in patients treating lateral epicondylitis.19,20 Approximately 2 ml of PRP was injected in the most heterogeneous area of the tendon on B mode. Small amount of PRP, which was not applied into the treated tendons, was analyzed in the Laboratory for Haemostasis and Atherothrombosis (University Medical Centre, Ljubljana, Slovenia) for PRP compounds (
Open source program for image processing, ImageJ (NIH programs, USA) was used. Region of interest (ROI) was selected in each 8-bit DICOM gray scale image from the set of 6 consecutive slices of each affected tendon as shown in Figure 1. Extracted ROI were then analyzed within statistical program R v4.1.2 (R Core Team, Austria). Texture features extraction based on gray level run length matrix (GLRLM) were done with radiomics Image Processing Toolbox inside the R (Radiomics v 0.1.3) Statistical analysis involved mixed effect statistical modeling with the help of R package NLME
All patients stated at least some improvement of symptoms after PRP injection therapy. Laboratory analysis of PRP showed, that applied PRP consisted of average platelet concentration of 1954 × 103/μL (range 1524 × 103/μL – 2163 × 103/μL) and average leukocyte concentration of 24 × 103/μL (range 15,6 × 103/μL – 31,5 × 103/μL). Median score at PRTEE questionnaire for patients with epicondylitis before treatment was 65 (range 36 – 79), after treatment 26 (range 3 – 57) with a median improvement in score of 28. Median score at SPADI questionnaire for patients with shoulder problems before treatment was 47 (range 16 – 75), after treatment 12 (range 0–70) with a median improvement in score of 18.
Figure 2 shows detailed statistical analysis of eight GLRLM features in treated tendons (
Correlations according to the mixed effect model between clinical evaluation and changes in GLRLM features are shown in Figure 3. In the analysis it is seen that between among all used features GLRLM-LRLGLE has moderate positive and statistically significant correlation with clinical evaluation after PRP (
This study aimed to perform texture analysis of symptomatic tendinosis US images of supraspinatus and elbow common extensors tendons after PRP treatment. Several GLRLM features were analyzed and found that almost all used features were significantly improved after PRP treatment.
Computer-aided diagnosis tools (
In our study most of the values of GLRLM features were significantly altered already in short-time interval (
So far, several studies have been performed to follow-up the effect of various treatment options of tendinopathies. However, mostly these were semi-quantitative evaluations based on standard US criteria for tendinopathy, such as focal or diffuse loss of uniform tendon echotexture, thickening of the tendon, loss of fibrillar structure and neovascularity.22 In our study GLRLM avoids semi-quantitative assessment of tendinopathy based on “classic” US features and enabled to quantify properties of the tendon by their texture content. This approach enabled us to analyze tissue imaging and clinical outcome after PRP more objectively.
Despite still uncertain steps of PRP effects, in the short-term the factors released by the platelets most likely lower tissue inflammation and modulate the pain receptors sensibility.23 Afterwards, PRP favors the cell proliferation with collagen and matrix deposition, as well as tissue remodeling. The final outcome is tissue scar formation, which can help to restore tendon function.
In the study, two groups of tendons were treated (
All treated patients improved of tendinosis symptoms in rather short time prior to complete tendon remodeling. This effect could be associated also with high leukocyte concentration of the obtained PRP. We assumed that the leukocyte-rich content of PRP influenced the concentration of various cytokines and modulate local immune and inflammatory response similar as reported in previous studies.24
The study had several limitations. Firstly, the studied sample in this pilot study is rather small since some of the treated patients did not return to the follow up. Secondly, the observation period was relatively short. Although we observed clinical improvements after three months, remodulation of the treated tendons was probably not yet completed in this short period of time by means of texture analysis. Therefore, the next step would be to perform a similar study in a larger group with intermediate as well as longer observation time period using a comparable concept of texture analysis and clinical questionnaires. In the study the intraobserver variability was also addressed. It was lowered as much as possible by taking multiple consecutive slices of each tendon and placing the US probe in the similar positions regarding bony and soft tissue landmarks at the initial and posttreatment imaging. Finally, we studied only the effect of leukocyte-rich PRP compound and did not make any comparison between different PRP compound,
In conclusion, computer aided texture analysis of US tendinosis enabled to quantify tendon remodeling in short time period after PRP treatment, with the most pronounced effect in features, sensitive to changes in longitudinal tissue orientation. Features of GLRLM analysis have the potential to become useful imaging biomarkers to monitor spatial and time limited tissue response, however larger studies with similar protocols are needed.