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Ultrasound Biomicroscopy for the Detection of Early Osteoa rthritis in an Animal Model

Rationale and Objectives

Osteoarthritis (OA) is a common disease, and early diagnosis is essential for preventing further cartilage destruction and decreasing severe complications. Ultrasound biomicroscopy (UBM) is sensitive for detecting minute lesions in tissue because of its higher resolution, but its B-mode characterization of the early stage of OA has not been widely studied. The aim of this study was to determine the usefulness of UBM for detecting the early stage of OA using a rabbit model of early OA.

Materials and Methods

Eighteen adult New Zealand White female rabbits were used in this study, which included 12 rabbits that underwent transections of the left anterior cruciate ligament and six control rabbits. At 2, 4, and 6 weeks after surgery, four experimental rabbits and two control rabbits were euthanized. UBM was performed to evaluate the articular cartilage surfaces of the left knee, using a 55-MHz transducer. All the articular cartilage surfaces were independently assessed in blinded fashion by two radiologists for the severity of OA. The value of UBM, interobserver reliability, and the concordance between UBM and pathologic grades were determined.

Results

For the first radiologist, the sensitivity, specificity, positive predictive value, and negative predictive value of UBM for the diagnosis of OA were 91%, 83%, 89%, and 86%, respectively. For the second radiologist, the sensitivity, specificity, positive predictive value, and negative predictive value of UBM were 93%, 86%, 91%, and 89%, respectively. The concordance between UBM and pathologic grades for both radiologists was high (κ = 0.72 and 0.76), and the interobserver agreement was high (κ = 0.80).

Conclusions

UBM can be used to evaluate cartilage defects in an animal model, and further study is needed to determine whether this technique can be valuable for detecting early OA in humans.

Osteoarthritis (OA) is a common disease that can cause a loss of function and disability in adults . Early diagnosis is essential for preventing further cartilage destruction and decreasing the severe complications of this disease. Unfortunately, early changes in cartilage cannot be determined with radiography. Arthroscopy offers information only on the surface of articular cartilage, while possible degeneration of the deep cartilage and subchondral bone remains undetected. Ultrasound has been widely adopted to assess the articular cartilage, because of its noninvasiveness, easy access, and low cost . However, because the articular cartilage is a very thin tissue, it brings an inherent constraint between imaging spatial resolution and the penetration depth of conventional ultrasound, which is performed externally from the joint surface. Therefore, more and more researchers have become interested in a minimally invasive but more direct measurement of the articular cartilage using arthroscopy-based techniques . Quantitative high-resolution arthroscopic ultrasound imaging could provide a potential technique for the early diagnosis of OA. However, an uncontrolled, nonperpendicular angle of an ultrasound beam and the natural curvature of the cartilage surface may jeopardize the reliability of the ultrasound measurements .

Ultrasound biomicroscopy (UBM) has been shown to be sensitive for detecting minute lesions in tissue because of its higher resolution . But its B-mode characterization of the early stage of OA has not been widely studied . We hypothesized that B-mode UBM could be used for diagnosing early OA. The aim of this study was to determine the usefulness of UBM for detecting the early stage of OA using a standard surgical model of OA in rabbits.

Materials and methods

Animals and OA Model

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UBM

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Figure 1, Picture of the transducer showing how it was applied to the pathologic specimens.

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Reference Standard

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Statistical Analysis

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Results

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Table 1

Detection of OA in Rabbits on Ultrasound Biomicroscopy

First Radiologist Second Radiologist Pathology OA Lesions Normal OA Lesions Normal OA lesions 39 4 40 3 Normal 5 24 4 25

Data are the number of articular cartilage surfaces.

OA, osteoarthritis.

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Figure 2, Normal cartilage of a medial tibial plateau. (a) Normal cartilage was demonstrated as two sharp parallel hyperechoic lines, delimiting a hypoechoic area. (b) The matrix staining was homogeneously colored by safranin O. The long arrow shows the superficial zone of cartilage. The short arrow shows the interface between the bone and cartilage. (c) Matrix staining was homogeneously colored by toluidine blue. The long arrow shows the superficial zone of cartilage. The short arrow shows the interface between the bone and cartilage.

Figure 3, Early stage of osteoarthritis in a lateral femoral condyle. (a) Grade 1 of articular cartilage was demonstrated as a rough superficial interface on ultrasound biomicroscopy. (b) Fibrillation of the superficial layer of cartilage (long arrow) was showed on safranin O–stained section. The short arrow shows the interface between the bone and cartilage. (c) Fibrillation of the superficial layer of cartilage (long arrow) was shown on toluidine blue–stained section. The short arrow shows the interface between the bone and cartilage.

Figure 4, Early stage of osteoarthritis in a lateral femoral condyle. (a) Grade 2 of articular cartilage was demonstrated as diffuse increased echogenicity in the cartilage on ultrasound biomicroscopy. (b) A loss of safranin O staining was found in the superficial layer of cartilage (long arrow), and the superficial surface was uneven on the histologic section. The short arrow shows the interface between the bone and cartilage. (c) A loss of toluidine blue staining in the superficial layer of cartilage (long arrow) was found on the histologic section. The short arrow shows the interface between the bone and cartilage.

Figure 5, Advanced stage of osteoarthritis in a medial femoral condyle. (a) Grade 3 of articular cartilage was demonstrated as a partial cartilage thickness defect on ultrasound microscopy. (b) Histologic examination showed the defect of partial cartilage thickness (long arrow) and loss of safranin O staining in the superficial and mid layers of cartilage. The short arrow shows the interface between the bone and cartilage. (c) Histologic examination showed the defect of partial cartilage thickness (long arrow) and loss of toluidine blue staining in the superficial and mid layers of cartilage. The short arrow shows the interface between the bone and cartilage.

Table 2

Distribution of Ultrasound Biomicroscopy Grades and Pathologic Grades of Articular Cartilage Surfaces

First Radiologist Second Radiologist OARSI Grade Normal Grade 1 Grade 2 Grade 3 Normal Grade 1 Grade 2 Grade 3 Normal 24 5 0 0 25 4 0 0 Grade 1 4 7 3 0 3 9 2 0 Grade 2 0 2 21 0 0 3 20 0 Grade 3 0 0 0 6 0 0 0 6

Data are the number of articular cartilage surfaces.

OARSI, Osteoarthritis Research Society International.

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Discussion

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