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Articular Cartilage Imaging by the Use of Phase-Contrast Tomography in a Collagen-Induced Arthritis Mouse Model

Posted Jan 31, 2010 Updated Apr 7, 2023
By Yeom Sik Lee MD , Eun-A. Heo MD , Hong Young Jun MS , Sung Hoon Kang MS , Hun Soo Kim MD PhD , Myung Soo Lee MD PhD , Seung Jae Byun MD , Sang Ho Lee MS , Seong Hoon Park MD , Kwon-Ha Yoon MD PhD
9 min read

Rationale and Objectives

This study was designed to demonstrate the feasibility of the use of phase-contrast computed tomographic (CT) imaging for the identification of articular cartilage abnormalities of the knees in a mouse model of collagen-induced arthritis.

Materials and Methods

Arthritis was induced in nine male DBA/1 J mice by the intradermal injection of collagen. After 50 days, the nine mice were sacrificed, along with four mice that did not receive intradermal injections of collagen. Phase-contrast CT imaging using a microfocus x-ray source of the entire knee was performed. The images were evaluated by two blinded readers, and histopathologic grades were considered the reference standard. The phase-contrast CT images of cartilage were graded 0, I, or II. Evaluation of the grading agreement between the phase-contrast CT images and histopathologic findings was performed using correlation analysis.

Results

Phase-contrast CT images highly reflected the subchondral bone status in the assessment of articular cartilage abnormalities in the mouse model of collagen-induced arthritis. Three-dimensional reformed images showed the articular surface and subchondral bony status of the knee joints. On the basis of the histopathology of the 26 knee joints, 12 joints were grade 0, six joints were grade I, and eight joints were grade II. Grading agreement between the use of the phase-contrast CT images and histopathologic results was high ( r = 0.76).

Conclusions

Phase-contrast CT imaging using a microfocus x-ray source offers a promising tool for the assessment of articular cartilage abnormalities of the knees in a mouse model.

The early diagnosis of arthritis allows patients to begin treatment before disease progression leads to disability. For inflammatory arthritis, the articular cartilage is damaged before the subchondral bone . Many imaging methods have been used to evaluate inflammatory arthritis. Conventional radiography and computed tomographic (CT) imaging are very limited in the depiction and evaluation of articular cartilage directly. Until recently, magnetic resonance imaging has been the most promising tool for cartilage imaging, especially to obtain high-resolution images. However, alternative imaging techniques to evaluate cartilage should provide diagnostic benefits for clinical use and basic research. Thus, a new cartilage imaging method with excellent diagnostic performance and practical utility would be desirable.

Recently, phase-contrast x-ray imaging has been regarded as a new imaging method that provides soft-tissue discrimination at micrometer resolution, with lower radiation doses than required by conventional absorption techniques . Conventional x-ray imaging uses differences in the x-ray absorption coefficients of tissues, but the difference is small for soft tissue, resulting in poor image contrast. Phase-contrast x-ray imaging uses differences in the refractive indexes of different tissues, where the difference in the refractive index is high at the boundaries for different tissues, resulting in an edge enhancement effect . The phase shift cross-section is almost 1,000 times greater than the absorption cross-section, resulting in high image contrast . Several studies have demonstrated high image contrast of phase-contrast x-ray imaging using synchrotron radiation for cartilage and bone ( ), blood vessels , the breast ( ), and the lung . However, these studies remain almost completely restricted to the laboratory, and in particular, the studies have required the use of synchrotron radiation sources. Although a synchrotron radiation source can produce high-resolution images with short exposure times, such sources are available only at restricted facilities and are very inconvenient for users.

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Materials and methods

Murine Model of Collagen-induced Arthritis

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Phase-contrast CT System

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Image Analysis

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Histopathologic Correlation

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Statistical Analysis

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Results

Phantom Study of Phase-contrast CT Imaging

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Figure 1, ( a ) Phase-contrast computed tomographic image of the acetyl phantom at 7× magnification. The phase-contrast effect at the edge of the acetyl phantom is high for the brightness level and low for the darkness level on a gray value profile. ( b ) Gray value profiles at the edge range at 7× magnification ×7. The figure shows approximately 200 (arbitrary units [AU]) of the value of the phase-contrast effect at the edge.

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Phase-contrast CT Imaging of Articular Cartilage of the Arthritis Model

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Figure 2, The normal anatomy of articular cartilage. ( a ) Phase-contrast computed tomographic (CT) image shows the articular cartilage layer (arrows) of the femoral condyle and tibia plateau of the knee joint as homogeneous density with regular thickness. ( b ) A micro-CT image without magnification of the same specimen shows blurred articular surface and poor image contrast (arrows). ( c ) Hematoxylin and eosin stain of the specimen of articular cartilage corresponding to (a) demonstrates chondrocytes surrounded by ground substances and calcified layer of the cartilage anchoring the collagen bundles to the underlying bone (arrows) (magnification, 4.0×).

Figure 3, Grade 0 lesion. ( a ) Phase-contrast computed tomographic image shows a smooth border and homogeneous density with regular thickness of the articular cartilage of the knee joint (arrows). ( b ) Three-dimensional reformed images show a smooth articular surface and subchondral bony status of the knee joint. ( c ) Hematoxylin and eosin stain of the specimen corresponding to (a) confirms the presence of a smooth and regular thickened articular cartilage layer (arrows) without subchondral bone destruction (magnification, 4.0×).

Figure 4, Grade I lesion. ( a ) Phase-contrast computed tomographic image shows a partial defect and irregular thinning of the articular cartilage (arrows) without subchondral bone destruction. ( b ) Three-dimensional reformed image shows partial cartilage defects (arrows) within the articular surface of the knee joint. ( c ) Hematoxylin and eosin stain of the specimen corresponding to (a) confirms the presence of irregular thinning of the articular cartilage layer (arrows) without subchondral bone destruction (magnification, 4.0×).

Figure 5, Grade II lesion. ( a ) Phase-contrast computed tomographic image shows irregular articular surface density with a round or ovoid subchondral bone defect of the articular cartilage (arrows). ( b ) Three-dimensional reformed image shows an irregularly deformed articular surface with subchondral bony destruction in the knee joint (arrow). ( c ) Hematoxylin and eosin stain of the specimen corresponding to (a) confirms the presence of multifocal subchondral destruction (arrows) due to extensive synovial hyperplasia (magnification, 4.0×).

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Phase-contrast CT Images Correlated with Histopathology

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Table 1

Comparison of the Histologic and Phase-contrast CT Imaging Grades of 26 Knee Joints

CT Grade Histologic Grade 0 I II Total 0 12 0 0 12 I 0 4 2 6 II 0 0 8 8 Total 12 4 10 26

CT, computed tomographic.

The correlation coefficient of the two independent measurements was r = 0.76.

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Discussion

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Academic Radiology, Volume 17, Issue 2
Journals General Radiology
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