Three-Dimensional Quantitative Magnetic Resonance Imaging of Epiphyseal Cartilage Vascularity Using Vessel Image Features: New Insights into Juvenile Osteochondritis Dissecans

Abstract

We introduce a quantitative measure of epiphyseal cartilage vascularity and examine vessel networks during human skeletal maturation. Understanding early morphological changes in the distal femoral condyle is expected to provide information on the pathogenesis of developmental diseases such as juvenile osteochondritis dissecans.

Methods: Twenty-two cadaveric knees from donors ranging from 1 month to 10 years of age were included in the study. Images of bone, cartilage, and vascularity were acquired simultaneously with a 3-dimensional gradient-recalled-echo magnetic resonance imaging (MRI) sequence. The secondary ossification center volume and total epiphysis cartilage volume ratio and articular-epiphyseal cartilage complex and epiphyseal cartilage widths were measured. Epiphyseal cartilage vascularity was visualized for 9 data sets with quantitative susceptibility mapping and vessel filtering, resulting in 3-dimensional data to inform vessel network segmentation and to calculate vascular density.

Results: Three distinct, non-anastomosing vascular networks (2 peripheral and 1 central) supply the distal femoral epiphyseal cartilage. The central network begins regression as early as 3 months and is absent by 4 years. From 1 month to 3 years, the ratio of central to peripheral vascular area density decreased from 1.0 to 0.5, and the ratio of central to peripheral vascular skeletal density decreased from 0.9 to 0.6. A narrow, peripheral vascular rim was present at 8 years but had disappeared by 10 years. The secondary ossification center progressively acquires the shape of the articular-epiphyseal cartilage complex by 8 years of age, and the central areas of the medial and lateral femoral condyles are the last to ossify.

Conclusions: Using cadaveric pediatric knees, we provide quantitative, 3-dimensional measures of epiphyseal cartilage vascular regression during skeletal development using vessel image features. Central areas with both early vascular regression and delayed ossification correspond to predilection sites of juvenile osteochondritis dissecans in this limited case series. Our findings highlight specific vascular vulnerabilities that may lead to improved understanding of the pathogenesis and better-informed clinical management decisions in developmental skeletal diseases.

Clinical relevance: This paradigm shift in understanding of juvenile osteochondritis dissecans etiology and disease progression may critically impact future patient management. Our findings highlight specific vascular vulnerabilities during skeletal maturation in a group of active young patients seen primarily by orthopaedic surgeons and sports medicine professionals.

Fig. 1

Figs. 1-A and 1-B Anatomical and vascular MRI scans of a 1-month postnatal knee joint. Fig. 1-A A representative magnitude image from the 3-dimensional GRE sequence depicts the femur and tibia of a knee joint in the coronal orientation. Epiphyseal cartilage (EC) and articular cartilage (AC) are of high signal intensity and together encompass the articular-epiphyseal cartilage complex where low-intensity vascular canals (indicated by an asterisk) traverse the EC only. There is a small, low-intensity secondary ossification center (SOC). The popliteus tendon (P) marks the lateral aspect of the knee. Fig. 1-B The corresponding quantitative susceptibility mapping post-processed maximum intensity projection demonstrates the vascular network of the EC in both the femur and tibia. S = superior, L = lateral, M = medial, and I = inferior.

Fig. 2

Secondary ossification center development with age. Representative stages of the development of the secondary ossification center in the axial plane at the level of the maximal trochlear depth. The shape of the secondary ossification center changes from round (1 month), to oval (3 months), to congruent ovals (2 years), to aviator glasses (5 years), to finally assuming the asymmetric (about the midline) contour of the overlying cartilage template of the adult distal femur (8 years). A = anterior, L = lateral, M = medial, and P = posterior.

Fig. 3

The secondary ossification center (SOC) and total epiphysis volume (TEV) change with age. The percentage of volume ratio of the SOC (bone) to TEV (cartilage) increases linearly with age for both sexes.

Fig. 4

Figs. 4-A, 4-B, and 4-C Epiphyseal cartilage vascular visualization with MRI. A = anterior, L = lateral, M = medial, and P = posterior. A representative slice of the 3-dimensional GRE MRI data set shows the magnitude anatomical image (Fig. 4-A) and vasculature (Fig. 4-B) after quantitative susceptibility mapping post-processing. Vessel-enhancement filters and semiautomatic segmentation allows for the vascular supply of the distal femoral epiphyseal cartilage to be visualized as a color-coded vascular network image (Fig. 4-C) (lateral peripheral = green vessels, central = white vessels, and medial peripheral = red vessels).

Fig. 5

Distal femoral epiphysis vascular canals at 3-month postnatal development. A volume rendering demonstrates the 2 distinct segmental distributions of the vascular canals with an intervening avascular zone (indicated by the asterisks) surrounding the small secondary ossification center (SOC). The peripheral vascular network consists of the lateral and medial vascular canals, and the central vascular network (arrows) consists of the intercondylar vessels. The inset of a higher-magnification image shows a group of regularly spaced vessels that extend from the periphery to the avascular zone (indicated by the asterisk) in a cluster of terminating small sinusoidal buds (carets). The avascular zone is interposed between the peripheral and central vascular networks; no anastomoses are observed between these 2 sources of blood supply. A = anterior, L = lateral, M = medial, and P = posterior.

Fig. 6

Visualizations and density changes in vascular network with age. Maximum-intensity projections of the quantitative susceptibility mapping-post-processed, vessel-enhanced maps from 6 selected cadaveric specimens with increasing age are shown in the top 2 rows. The vasculature is color-coded according to the vascular network (lateral peripheral = green vessels, central = white, and medial peripheral = red). The embedded table summarizes the density ratio measurements (vascular area density and vascular skeletal density) of the central network to the peripheral (medial and lateral) network. No central network was observed in the specimens from donors who were ≥4 years of age. By 8 years of age, there was a small, residual peripheral vascular network. At 10 years of age, no epiphyseal cartilage vascularity could be detected. A = anterior, L = lateral, M = medial, P = posterior, and n/a = not available.

Fig. 7

Vascular density compared with specimen age. Quantitative vascular density measurements (displayed as a ratio of the central vascular network to the peripheral vascular network) for the selected 6 specimens containing a central vascular network (<3 years of age). A linear fit showed a decreasing trend in the central and peripheral vascular area density (VAD) and vascular skeletal density (VSD) ratios with specimen age up to 3 years. a.u. = arbitrary units.

Fig. 8

MRI visualization of the vascular supply to the predilection site. A representative axial slice of the distal part of the femur from the 3-dimensional GRE MRI data set from a 5-year-old specimen shows the magnitude image (gray scale) overlaid with the vascular post-processed image (red scale). The central vascular supply has vanished. The ossification front has reached the central aspect of the intercondylar notch and grew wider in the transverse than the anteroposterior dimension leaving the thickest not-yet-ossified cartilage at the weight-bearing aspect of the joint. The articular cartilage (denoted by a light blue dotted line) is free of vessels; therefore, the subarticular epiphyseal cartilage vascular supply has to travel from the peripheral extra-articular perichondrium in parallel to the articular surface to reach the central aspect of the medial and lateral femoral condyles. This leaves these areas at the central aspect of the medial femoral condyle (wider), and to a lesser degree the lateral femoral condyle, most distant to the origin of their peripheral vascular supply. The predilection site of juvenile osteochondritis dissecans (highlighted) and a medial-lateral running vascular canal from the peripheral vascular supply is marked (denoted by an asterisk). A = anterior, L = lateral, M = medial, and P = posterior.