Cartilage MRI T2∗ relaxation time and perfusion changes of the knee in a 5/6 nephrectomy rat model of chronic kidney disease  C.-Y. Wang, Y.-J. Peng, Y.-J. Hsu, H.-S. Lee, Y.-C. Chang, C.-S. Chang, S.-W. Chiang, Y.-C. Hsu, M.-H. Lin, G.-S. Huang  Osteoarthritis and Cartilage  Volume 25, Issue 6, Pages 976-985 (June 2017) DOI: 10.1016/j.joca.2016.12.019 Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 A schematic illustration of the protocol design in this study. (↓) indicates MRI (⇩); indicates histologic examination. Osteoarthritis and Cartilage 2017 25, 976-985DOI: (10.1016/j.joca.2016.12.019) Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 ROI in a representative knee cartilage. (A) ROIs (white) in the articular cartilage were selected using the DCE first-frame and MRI T2∗ first-echo sagittal images. The lateral and medial articular cartilages were measured in the same manner. (B) The DCE results (amplitude A map) of medial femoral and tibial cartilages of the right knee in 44-week-old control and CKD rats. Significant hypoperfusion in knee articular cartilage can be noted in the CKD group (lower) but not in the control group (upper). Osteoarthritis and Cartilage 2017 25, 976-985DOI: (10.1016/j.joca.2016.12.019) Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 Plots of three perfusion parameters and MRI T2* values (mean ± SD) for the lateral (left) and medial (right) cartilages of the control and CKD groups. (A) Amplitude value A (unit: au) (B) Elimination constant kel (unit: min−1), (C) Permeability rate constant kep (unit: min−1), and (D) T2* (unit: msec) values at weeks 0, 8, 12, 16, 24, 30, 36 and 44 measured in the right knees of all rats. Asterisks indicate significant differences (P < 0.05). Significantly decreased blood volume parameter A and washout parameter kel can be observed starting from week 12 in (A) and (B). No significant difference was shown in permeability rate constant kep (C). Significantly increased MRI T2∗ value can be observed starting from week 16, reflecting the extracellular matrix change of cartilage (D). Osteoarthritis and Cartilage 2017 25, 976-985DOI: (10.1016/j.joca.2016.12.019) Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

Fig. 4 Histologic and immunohistochemical appearance of knee cartilage in the control and CKD groups. (A) Normal appearing vessel wall of the popliteal artery in the control group, but thicker vessel wall and hypertrophic smooth muscle cells were found in the CKD groups (right) (all images in A magnified ×200). (B) The femoral and tibial cartilages stained by safranin O (upper row) and Masson's trichrome (lower row) in the control and CKD groups. In the CKD group, the femoral and tibial cartilages of the right knee show degeneration characterized by proteoglycan loss and surface fibrillation. No significant changes are seen on the femoral and tibial sides of the knee in the control group (magnification ×200). (C) Immunohistochemical stain for alpha-smooth muscle actin of the subchondral bone marrow from a 44-week-old CKD rat (right) and a control rat (left). Images were captured using the dedicated software Image Scope (Aperio®, Leica Microsystems, Nanterre, France). The number of vessels in the subchondral bone marrow was elevated in CKD rats compared to control rats (green spots in upper row). However, the vascular diameter and wall thickness were decreased in CKD group (lower row), arrows: small vessels, arrow head: capillaries. Osteoarthritis and Cartilage 2017 25, 976-985DOI: (10.1016/j.joca.2016.12.019) Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions