Browsing by Author "Roth, Bradley J"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Cerebral Waste Clearance: Measurements and Applications
    (2023-01-01) Kaur, Jasleen; Xia, Yang; Roth, Bradley J; Zhang, Li; Zhang, Zhenggang; Chopp, Michael
    Cerebral Waste clearance (CWC) is an essential process for brain homeostasis, which is required for the healthy functioning of all cerebrovascular and parenchymal brain cells. This dissertation features our current understanding of CWC, both within and external to the brain parenchyma. We describe the role of the cerebrospinal fluid (CSF) and its exit routes in mediating CWC. Recent discoveries of the glymphatic system and meningeal lymphatic vessels (mLVs), and their relevance to CWC and various neurological conditions are highlighted. Controversies related to CWC research and potential future directions are presented. This dissertation is divided into seven chapters that discuss investigations that used magnetic resonance imaging (MRI) and confocal microscopy imaging to evaluate the recently identified CWC routes, namely the glymphatic system and the mLVs. The dissertation begins with an introduction (Chapter- 1). It proceeds with background (Chapter- 2) based on two published peer-reviewed ‘review’ articles, and three research projects based on one submitted, one published ‘original research’ articles (Chapters- 3, 4) and one project with negative results (Chapter- 5). Among the three projects described in this dissertation, the first project (Chapter- 3) aimed to investigate the controversy of glymphatic convective bulk flow in the interstitial spaces and explore the association of perivascular macrophages (PVMs) in assisting the glymphatic system for CWC. Our findings solidify the glymphatic system hypothesis and indicate the interaction of PVMs with the glymphatic CSF influx along the arteries and glymphatic CSF efflux along the veins. The second project (Chapter- 4) aimed to examine the changes in the glymphatic system in rats with glioblastoma multiforme (GBM) and our results identify reduced glymphatic influx and clearance due to GBM. The third project (Chapter- 5) aimed to assess the mLVs as a potential efflux pathway of the glymphatic system under healthy and diabetic mellitus (DM) conditions. Our results suggest that mLVs are not the major efflux pathway of the glymphatic system, which is a negative result. The dissertation then discusses a translational issue for clinical MRI evaluation of the glymphatic system (Chapter- 6) based on a submitted ‘review’ article and concludes with a summary and future directions (Chapter- 7).
  • Thumbnail Image
    Item
    Multi-Resolution Study of Topographical and Zonal Properties of Osteoarthritis in Articular Cartilage Using Microscopic MRI and Polarized Light Microscopy
    (2022-03-22) Badar, Farid-Ahmed Wajihuddin; Xia, Yang; Roth, Bradley J; Khain, Evgeniy; Jiang, Quan; Bowyer, Susan M
    Articular cartilage is a thin layer of connective tissue found in diarthrodial joints that overlay the opposing ends of bones and acts as lubricating surfaces to distribute stress and reduce friction with the help of synovial fluid. Hyaline cartilage contains an abundance of water molecules that are essential to the behavior and function of cartilage, the negatively charged proteoglycans that influence the biomechanical properties of the tissue, and the collagen fibers that act as the rebar or reinforcement bars to preserve the structural integrity of the tissue. Cartilage supports the applied load and distributes stress based on its intrinsic material properties, together with its underlying bone. At different surface locations of any single diarthrodial joint, the properties of cartilage are prone to have many morphological and molecular variations topographically, which are mainly due to the patterns of mechanical loading for any specific joint. Any change in the morphological and molecular properties of the cartilage and bone is likely to directly impact the clinical diagnoses of joint diseases such as osteoarthritis (OA). In addition to the topographical variations, cartilage also has a number of depth-dependent variations over its thin thickness, which begins in the non-calcified cartilage with articular laminae and the unequal thickness of sub-tissue zones. Conceptually, the non-calcified cartilage is commonly subdivided based on the orientations of collagen fibers and chondrocytes, into three histological zones. They are the superficial (SZ), transitional (TZ), and radial (RZ) zones. The non-calcified cartilage interfaces with the calcified cartilage and subchondral bone plate (SBP) through the tidemark (TM). This dissertation has seven chapters, which describe a number of multi-resolution projects that use high-resolution imaging to determine the topographical and depth-dependent variations in cartilage, in order to diagnose OA at its earliest stages. The dissertation begins with a brief introduction of background and literature review (Chapters 1-2), continues with the description of the materials and methods (Chapter 3), and summarizes three published peer-reviewed journal articles (Chapters 4-6). The dissertation ends with a summary and comments on future directions (Chapter 7). Among the three research projects described in this dissertation, the first project (Chapter 4) investigates the improvement in the OA detection in cartilage by the interpolation of T2 images, in the situation when the native MRI resolution is insufficient to resolve the depth-dependent T2 characteristics in articular cartilage. The second project (Chapter 5) establishes the topographical and zonal T2 patterns of multi-resolution MRI in medial tibial cartilage in a canine model of OA, initiated by an anterior cruciate ligament (ACL) transection surgery, which was studied after 8-weeks and 12-weeks post-surgery. The third project (Chapter 6) quantifies the interface region between the non-calcified cartilage and the subchondral bone plate, which includes the deep portion of the non-calcified articular cartilage and the zone of calcified cartilage (ZCC) using a dual-modality microscopic imaging study.