Patients with late‐stage Kellgren‐Lawrence knee osteoarthritis received a single intra‐articular injection of 1, 10, or 50 million bone marrow mesenchymal stromal cells (BM‐MSCs) in a phase I/IIa trial to assess safety and efficacy using a broad toolset of analytical methods. Besides safety, outcomes included patient‐reported outcome measures (PROMs): Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); contrast‐enhanced magnetic resonance imaging (MRI) for cartilage morphology (Whole Organ MRI Scores [WORMS]), collagen content (T2 scores), and synovitis; and inflammation and cartilage turnover biomarkers, all over 12 months. BM‐MSCs were characterized by a panel of anti‐inflammatory markers to predict clinical efficacy. There were no serious adverse events, although four patients had minor, transient adverse events. There were significant overall improvements in KOOS pain, symptoms, quality of life, and WOMAC stiffness relative to baseline; the 50 million dose achieved clinically relevant improvements across most PROMs. WORMS and T2 scores did not change relative to baseline. However, cartilage catabolic biomarkers and MRI synovitis were significantly lower at higher doses. Pro‐inflammatory monocytes/macrophages and interleukin 12 levels decreased in the synovial fluid after MSC injection. The panel of BM‐MSC anti‐inflammatory markers was strongly predictive of PROMs over 12 months. Autologous BM‐MSCs are safe and result in significant improvements in PROMs at 12 months. Our analytical tools provide important insights into BM‐MSC dosing and BM‐MSC reduction of synovial inflammation and cartilage degradation and provide a highly predictive donor selection criterion that will be critical in translating MSC therapy for osteoarthritis. Stem Cells Translational Medicine 2019;8:746&757

Qualitative and quantitative T2 mapping helped differentiate hyaline cartilage from reparative fibrocartilage after cartilage repair at 1.5-T MR imaging.

Traditional T2-based imaging techniques are geared toward imaging long-T2 species. Traditional techniques are, therefore, not optimal in clinical situations where the information of interest lies in the short-T2 species. T2-selective RF excitation (TELEX) is a technique for obtaining a T2-based contrast that highlights short-T2 values while suppressing long-T2 values-opposite to traditional T2 contrast. Previously, TELEX has been demonstrated qualitatively to highlight only very short-T2 values (T2 approximately 0.001 s). When applied to longer T2 values (T2 > or = 0.01 s), TELEX becomes sensitive to deltaB0 non-uniformities. This restricts its application to problems in which the T2 of interest is very short. In this study, TELEX is characterized quantitatively. Furthermore, a bandwidth broadening scheme is developed that reduces the deltaB0 sensitivity of TELEX. This permits the technique to be applied to longer T2 values. The capabilities and limitations of a practical implementation of TELEX are discussed.

Current applied to wire coils wound at the tip of an endovascular catheter can be used to remotely steer a catheter under magnetic resonance imaging guidance. In this study, we derive and validate an equation that characterizes the relationship between deflection and a number of physical factors: theta/sin(gamma-theta) = nIABL/EI(A) where theta is the deflection angle, n is the number of solenoidal turns, I is the current, A is the cross-sectional area of the catheter tip, B is the magnetic resonance (MR) scanner main magnetic field, L is the unconstrained catheter length, E is Young's Modulus for the catheter material, and I(A) is the area moment of inertia, and y is the initial angle between the catheter tip and B. Solenoids of 50, 100, or 150 turns were wound on 1.8 F and 5 F catheters. Varying currents were applied remotely using a DC power supply in the MRI control room. The distal catheter tip was suspended within a phantom at varying lengths. Images were obtained with a 1.5 T or a 3 T MR scanner using "real-time" MR pulse sequences. Deflection angles were measured on acquired images. Catheter bending stiffess was determined using a tensile testing apparatus and a stereomicroscope. Predicted relationships between deflection and various physical factors were observed (R2 = 0.98-0.99). The derived equation provides a framework for modeling of the behavior of the specialized catheter tip. Each physical factor studied has implications for catheter design and device implementation.