Background
Progressive articular cartilage defects in the knee are a major cause of pain, disability, and medical expenses in the general population and particularly in the elderly [
1]. Precise assessment of cartilaginous abnormality is important to determine the appropriate treatments, e.g., osteotomy, mosaicplasty, drugs, and autologous chondrocyte transplantation [
2]. Ultrasound (US) is widely available and relatively inexpensive and has proven to be a useful modality for the routine clinical assessment of joint diseases [
3]. US is radiation-free and non-invasive and allows dynamic assessment of moving structures [
4]. Previous studies evaluated the feasibility and diagnostic value of US for detecting cartilaginous defects [
5‐
15]. Previous studies reported associations of US with histologic and arthroscopic classifications of cartilage defects [
11,
13], and with an acceptable diagnostic performance [
14], suggesting that knee US is a promising technique for screening degenerative changes of articular cartilage in patients with osteoarthritis (OA) [
14]. Nevertheless, the correlations observed in previous studies were low, with coefficients of 0.262–0.655 [
13,
14] and could be due to the selection of the indicators, the selection of US systems, and the experience of the raters. In addition, negative predictive values (NPV) remained low (23.8–45.8%), implying that a negative finding using US does not rule out cartilage degenerative changes [
14]. Although a positive finding in US is a strong indicator of arthroscopic degenerative changes of cartilage [
14], the technique still needs improvements before routine clinical use.
Previous assessments were performed with a transducer capable of the highest frequency available for routine clinical use, already resulting in the highest sensitivity possible [
13,
14]. The diagnostic accuracy of US is often dependent upon the scanning approach in different US indications [
16‐
18]. Therefore, we hypothesized that improvement of the scanning technique could enhance US diagnostic value. Indeed, previous studies used a fixed flexed knee (e.g., 120°) with transverse scanning only [
13,
14], but the knee flexion angle influences the correlation between US and histologic classification of cartilage defects, although the optimal angle remains unknown [
13]. In addition, since only transverse scanning was applied, it remains unclear whether longitudinal scanning could offer more benefits, especially when depicting the condyle [
14].
Therefore, this study aimed to assess a novel US scanning approach in evaluating knee femoral cartilaginous defects, compared with magnetic resonance imaging (MRI, commonly used for knee imaging) and arthroscopy (gold standard).
Discussion
In this study, we aimed to improve the diagnostic accuracy of US for the diagnosis of knee lesions with the intention of improving the accessibility and decreasing the costs of knee examination associated with MRI and arthroscopy, particularly for outpatients. Nevertheless, MRI and arthroscopy are still necessary. Therefore, this study assessed the diagnostic value of a novel US scanning approach in evaluating knee femoral cartilaginous defects and found that it allows a similar diagnostic performance as routine MRI, but with improved NPV compared with previous US scanning approach, which is of clinical significance. Different articular surfaces of the femur can be accessible with an external US probe by varying the angle range of knee flexion [
23‐
25]. Interestingly, the novel scanning approach had similar sensitivity, specificity, and accuracy compared with MRI for detecting lesions on the whole femoral cartilage and individual articular surfaces. In addition, moderate agreement was obtained between grades assigned by arthroscopy and US.
In the present study, a substantial interobserver agreement was observed, while similar PPVs and higher NPVs were obtained in comparison with recent reports [
13,
14]. The improved NPV (i.e., decreased false-negative rate) could be a consequence of more visibility of the femoral cartilage in the novel scanning approach. The fairly low NPV reported by Saarakkala et al. [
14] is probably not related to an intrinsic limitation of the US itself or a need for higher resolution imaging but rather a lack of thorough observation of the overall femoral cartilage. An available acoustic window is the most important factor for US examination. The difficulty in visualizing the whole femoral cartilage due to the shadow of the patella and tibia is a major disadvantage. By using multiple knee angles, the novel approach markedly decreased false-negative femoral cartilage defect diagnoses.
In full extension (0°), the patella rests over the supratrochlear fat pad and is almost completely proximal to the superior border of the femoral articular cartilage [
22,
23]. In this position, US can show the cartilage of the anterior and posterior femoral condyles but not the trochlear surface and weight-bearing femoral condyles due to the interference of the patella and tibia. In 10°–20° flexion, the patella first hugs the femoral shaft closely then slips distally and always remains in contact with the trochlear surface of the femur [
22,
23], which may lead to poor visibility of most parts of the femoral articular surfaces. At approximately 135° of flexion, the patella reaches as far as the intercondylar notch [
23]. At this time, good exposure of the entire trochlear surface and most parts of the lateral and medial condyles can be achieved. Therefore, scanning on minimum (0°) and maximum (≥ 135°) angles of the knee flexion may provide a more thorough scan of the femoral cartilage than those using only a fixed flexed knee (e.g., 120°).
MRI is considered a method of choice for thorough evaluation of cartilage morphology, but its routine use in all symptomatic patients with clinical suspicion of knee cartilage defects is limited due to unavailability in many district and community hospitals in China and high costs (in terms of money and time) [
26]. Therefore, the application of the simple, widely available, and inexpensive US technique as the initial screening method for femoral cartilage lesions could be more appropriate. The novel US approach proposed here may satisfy the above requirements and can be used as an initial screening modality to provide a morphological assessment of the femoral articular cartilage in outpatient clinics.
As a non-invasive imaging modality, the novel approach needed further clinical validation. Therefore, the novel approach was compared with MRI, which is probably the most important method for cartilage imaging [
26]. Previous comparative studies [
27,
28] between US and MRI mainly focused on the thickness measurement of femoral cartilage, an important defect indicator, and showed a significant correlation (coefficients = 0.44–0.84). Comparison of US and MRI was further assessed in the present study; although a relatively lower detection rate of grade 1 defects was observed, the novel approach showed similar diagnostic ability for the detection and classification of cartilage defects compared with routine 2D FSE MRI, with a significant agreement for grading lesions.
The first major problem is that although the novel approach allows a significant decrease of false-negative diagnoses, it should be highlighted that the risk of false negatives was still as high as 26.7–30.5%, representing the majority of erroneous diagnoses. This likely results from the inability to visualize the lateral and medial condyles near the intercondylar notch, even at the maximum angle (e.g., 135°) of the knee flexion, due to their continuous articulation with the lateral and odd facet of the patella [
15]. Thus, defects in these locations were the major cause of false negatives, as none of them was detected. Therefore, the blind areas of US have been improved by using varying flexion (0–135°) rather than a fixed flexion (120°), but the novel approach still needs to be improved. Patients suspected to be with cartilage defects should undergo additional diagnostic modalities, e.g., MRI, even with a negative US finding to verify the cartilage status.
The second major problem is that only femoral surfaces can be seen by US, not the patellar and tibial surfaces, which precludes the technique from providing an overall assessment of the knee articular cartilage. Nevertheless, strong correlations (Pearson’s correlation coefficients = 0.75–0.77) between volume changes in femoral cartilage and that in tibial cartilage in OA patients have been reported [
29], indicating that evaluating one of the two features should be adequate. Therefore, US findings from the femoral cartilage might be reliable for evaluating arthritic cartilage changes of the tibial cartilage in clinical practice.
The US systems and technique are possible sources of error in US, as well as the operator. Although similar diagnostic accuracy between the novel approach and MRI was presented here, a substantial number of patients with small or superficial lesions (grade 1 defects) were misdiagnosed or missed by the US. Indeed, the US equipment available for routine clinical use can only assess conspicuous morphological changes of cartilage, not determining its internal characteristics, while MRI can. Therefore, subtle morphological changes in the early stage of cartilage defects might explain the misdiagnoses. More advanced equipment and techniques (e.g., a 50-MHz transducer, which can detect layers in immature cartilage [
30]) may provide a solution. Further studies are necessary to verify this hypothesis. Another issue is operator dependency, a known problem in US examination [
31]. As shown above, the difference in overall sensitivity was obtained between the two radiologists participating in this study. Therefore, a standardized training to learn the correct scanning approach and associated diagnoses is essential to avoid misdiagnoses or missed diagnoses.
There were some limitations to this study. First, although routine 2D FSE MRI sequences were performed as previously described [
32‐
34], it may be argued that this study underestimated the actual diagnostic ability of MRI, as it is not optimal for cartilage evaluation due to anisotropic voxels, section gaps, and partial volume effects [
26]. In addition, several MRI techniques are available to facilitate the assessment of the femoral cartilage for changes of morphology [
35‐
37] and even biochemical composition [
38,
39]. The results of MRI achieved in such sequences may be more favorable than those reported here. Nevertheless, since the cause of pain or disability of the knee is frequently multifactorial or unknown, 2D FSE sequences are most commonly applied in the clinical setting for initial examinations. In this study, we simulated a hypothetical situation of the first-time examination, which optimized the likelihood of screening cartilage defects.
Another limitation is that the same cartilage lesion could be attributed to different sites between US and MRI or arthroscopy. To minimize such discrepancies, the same standard schematic drawing of the femoral cartilage surfaces was used for all techniques. Nevertheless, a lesion located on the very edge of three articular surfaces would be likely assigned to different surfaces in various examination methods. Therefore, an overall assessment of the femoral cartilage from all three sites is necessary before the diagnosis and subsequent treatment of cartilage lesion; this is not affected by the possible misplacement. Further studies regarding treatment evaluation are required to target the precise lesion localization of cartilage.
In addition, the correlation between US findings and other assessment tools was not established. Indeed, in this initial study, we prioritized the associations of US with arthroscopy (gold standard) and MRI (most important imaging modality of cartilage). In the future, the correlation between the novel US scanning approach and clinical assessment should be evaluated for its recommendation in routine clinical use, including evaluation of degenerative changes and therapeutic effects.
The aim of the present study was to investigate the value of US as a screening tool for cartilage defects in patients with a chief complaint of knee pain (without any previous examination and diagnosis). It is indeed possible that some patients were not definitely diagnosed with OA. On the other hand, cartilage degeneration caused by OA may also present as cartilage defect. Therefore, it could be hypothesized that OA will not directly affect the capability of the US detection of cartilage defects, but this specific point will have to be examined in the future.