BME PhD Prospectus Defense - Lauren Mangano

10:00 am on Wednesday, April 30, 2014
110 Cummington Mall, Room 245
Prof Elise Morgan, ME (Advisor, Chair)
Prof Dimitrije Stamenovic, BME
Prof Mark Grinstaff, BME
Prof Louis Gerstenfeld, School of Medicine, Orthopaedic Surgery

Title: "Non-invasive assessment of cartilaginous tissues in small animal models of injury and disease"

Cartilage is integral to skeletal function, in development, growth, healing, and homeostasis. While micro-computed tomography (ÁCT) provides three-dimensional, non-destructive information about the microstructure, morphology, and composition of bone, this imaging modality has been unable to provide similar information about cartilage. Because of its low x-ray attenuation, cartilage is instead traditionally characterized by histology, a method that is inherently two-dimensional and destructive, or by magnetic resonance imaging (MRI), a method that has inadequate resolution for small animal studies and limited ability to characterize bone.
Recently, a cationic contrast agent specific to cartilage whose attenuation is correlated to content of glycosaminoglycan (GAG), a molecule abundant in healthy cartilage, has been developed. Using contrast enhanced ÁCT (CECT), the morphology and composition of bone and cartilage can be characterized simultaneously. This method has the potential to provide information about cartilage composition and morphology that is otherwise not available using non-destructive methods. CECT can therefore be used to study a range of animal models of injury and disease. Thus far, CECT has been used to study the fracture callus in mice, and to study articular cartilage in the context of osteoarthritis.

In this project, I will study two additional injury and disease models involving cartilage that are yet to be explored using CECT, growth plate injury and rheumatoid arthritis, and build upon previous work on fracture healing. Injury to the cartilaginous growth plate in children results in formation of bony bridges and disturbance of growth. Rheumatoid arthritis, an inflammatory autoimmune disease, results in destruction of cartilage and bone in the joints. ÁCT-based finite element models of the fracture callus are limited by estimates of callus stiffness. CECT of the fracture callus can provide the composition information to fill this gap in knowledge.

The goal of this project is to apply CECT to understand how the morphology and composition of cartilage responds to injury and disease. The project will consist of three aims, each focused on an injury or disease model in mice. First, I will quantify the response of the growth plate cartilage to a pinhole injury, using CECT to detect changes in growth plate morphology, including formation of bony bridges. In this aim, I will use histology as a comparison to CECT results. Second, I will determine the role of the A2B adenosine receptor in rheumatoid arthritis by quantifying bone and cartilage degradation via ÁCT and CECT in a collagen antibody-induced model. In this aim, I will use a both transgenic mice and pharmacological inhibitors to elucidate the role the A2B adenosine receptor’s role. Third, I will develop a finite element model of the fracture callus based on measures of callus stiffness, composition, and morphology from CECT and microindentation. In this aim, CECT will be applied in vivo.

This research will address a range of clinically relevant questions related to cartilage using a three-dimensional, non-destructive method. Moreover, the CECT methods developed as part of this research can be applied to additional cartilage injury and disease models.