Advanced qualitative and quantitative MRI methods can be utilized to study unique aspects of the developing skeleton that are important for diagnosis and better treatment of musculoskeletal diseases of pediatric and young adult patients.
INTRODUCTION: Currently musculoskeletal imaging of pediatric and young adult patients is underutilized in clinical practice and research applications. There are objective hurdles that markedly limit MSK imaging for this patient population. These limitations include the lack of appropriate radiofrequency coils for pediatric needs, specific requirements of fast, motion insensitive sequences are challenging to meet.
Normal tissue composition as well as injury patterns in the pediatric musculoskeletal system differ from adults. One of the most striking differences is the presence of vascularity within epiphyseal cartilage in children whereas adult articular cartilage is always avascular. Growth and development during skeletal maturation involves gradual replacement of the highly vascular epiphyseal cartilage (EC) with bone through a process called enchondral ossification. Epiphyseal vascular canals contain both arterioles and venules that provide nutrition and osteogenic cells [1, 2]. At the ends of long bones, the subarticular EC, adjacent to the secondary ossification center (SOC), and the overlying articular cartilage (AC) are together referred to as the articular-epiphyseal cartilage complex (AECC). While the AC is avascular, the extra-articular EC receives nutrients from a dense network of vascular supply. There is longstanding evidence that osteochondrosis (OC) in animals, is caused by an insult to the vascular supply of the EC and subsequent focal failure of enchondral ossification [3, 4] in the knee. The pathogenesis of the human equivalent disease called Juvenile Osteochondritis Dissecans (JOCD) is incompletely understood. Similarly for the hip, diseases of the developing hip such as Femoral Acetabular Impingement (FAI) and Legg-Calvé-Perthes disease (LCPD) are two examples of serious disorder that occur during skeletal maturation and are likely caused by abnormal physeal closure (FAI) and by interruption of blood supply to the developing femoral head in LCPD that leads to osteonecrosis.
MATERIALS & METHODS: Recent noninvasive MRI techniques, 3D susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM), use tissue-inherent phase information to visualize EC vascularity [5, 6]. SWI and QSM enable detection of the osseous, cartilaginous and vascular components of the developing skeleton within a single acquisition. “Vesselness” post-processing enabled quantitative vascular density measurements. This allowed for new studies on species comparisons and application of this technique to pediatric patients [5, 7, 8]. In an animal model of LCPD ischemia was induced and quantitative T1, T2 and T1ρ maps were acquired using a magnetization-prepared 2D FSE sequence. Relaxation time maps were generated in Matlab to assess femoral head osteonecrosis. Median relaxation times of T1, T2 and T1ρ for the (i) secondary ossification center SOC; (ii) epiphyseal cartilage (EC); and (iii) articular cartilage (AC).
RESULTS: This novel application of SWI and QSM - MRI allows detection of all components of the developing skeleton, the osseous, cartilaginous and vascular. We found that the distal femoral epiphyseal cartilage of the knee is supplied by two groups of vessels, peripheral and central, that do not anastomose. During gradual replacement of epiphyseal cartilage with bone, the asymmetrically thicker central medial femoral condyle and the lateral trochlear ridge are last to ossify. The central epiphyseal vascular bed regresses early during development, leaving these thicker areas of epiphyseal cartilage with progressively diminished vascular supply. Our results demonstrate the vascular development over time and highlight possible vulnerable regions that provide important information in the context of diseases of children and young adults, such as Osteochondrosis / Juvenile Osteochondritis Dissecans [9]. We found in a piglet model of LCPD that as early as 48 hours after induction of ischemia the T1ρ relaxation time maps showed pronounced increase in T1ρ in the SOC of the ischemic femoral head. In the SOC, T1ρ had the greatest percent increase, while T2 had the greatest percent increase in the epiphyseal and articular cartilage. Histological evaluation found evidence of ischemic injury to the SOC in the operated femoral heads. SWI and QSM allowed for detection of clinically relevant first repair response by visualizing neovascularization in the epiphyseal cartilage [10, 11].
SIGNIFICANCE/CLINICAL RELEVANCE: Our systematic basic science MRI studies on osteochondrosis and osteonecrosis in the developing skeleton as well as clinical pilot studies on young patients highlight the importance of attention to specific aspects of pediatric MSK imaging not applicable to adults, it demonstrates clinical feasibility and further technical development is needed to implement these studies into clinical practice.
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