Clinical Magnetic Resonance Imaging of Pancreatic Islet Grafts After Iron Nanoparticle Labeling

Abstract

There is a crucial need for noninvasive assessment tools after cell transplantation. This study investigates whether a magnetic resonance imaging (MRI) strategy could be clinically applied to islet transplantation. The purest fractions of seven human islet preparations were labeled with superparamagnetic iron oxide particles (SPIO, 280 lg/mL) and transplanted into four patients with type 1 diabetes. MRI studies (T2 * ) were performed prior to and at various time points after transplantation. Viability and in vitro and in vivo functions of labeled islets were similar to those of control islets. All patients could stop insulin after transplantation. The first patient had diffuse hypointense images on her baseline liver MRI, typical for spontaneous high iron content, and transplant-related modifications could not be observed. The other three patients had normal intensity on pretransplant images, and iron-loaded islets could be identified after transplantation as hypointense spots within the liver. In one of them, i.v. iron therapy prevented subsequent visualization of the spots because of diffuse hypointense liver background. Altogether, this study demonstrates the feasibility and safety of MRI-based islet graft monitoring in clinical practice. Iron overload (spontaneous or induced) represents the major obstacle to the technique.

Magnetic Resonance Imaging of Single Co-Labeled Mesenchymal Stromal Cells after Intracardial Injection in Mice

“…Already to date musculoskeletal MRI at 7.0 T can be carried out with a spatial resolution up to 156 × 156 × 500 μm [48], which is in the range of the 2 D GRE sequence applied for the abdominal imaging in mice. Furthermore, initial studies in patients receiving magnetically labeled cells using clinically approved iron oxide contrast agents have been reported [49,50]. These contrast agents may be also used to label MSC for single cell imaging [51].…”

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

“…By the same token, the influence of cell labeling on the long-term behavior of cells and the course of disease is currently unclear [155] and must be studied more closely in the future [156]. Successful in vivo detection and migration monitoring of SPIO-labeled cells was able to be demonstrated in numerous studies, e. g. in implanted hematopoietic, mesenchymal, or neuronal stem cells in the CNS [157], heart [158], liver [159], spleen [160], bone marrow [160], kidneys [161], joints [162], and muscles [163], endothelial progenitor cells [164], transplanted islet cells [165], and lymphocytic and moncytic cells (natural killer cells in oncological cell therapies [166]). Moreover, the migration of macrophages in apoptotic tissue replacement [167], tumors [168], or vascular aneurysms [169] was able to be visualized in vivo.…”

Improved dynamic response assessment for intra‐articular injected iron oxide nanoparticles

“…dUTE consisted of the acquisition and subtraction of two TEs (ultrashort UTE and short TE2) leading to positive contrast from short T 2 species and reduced signal elsewhere. Parameters here are 3D isotropic resolution matrix of 448 and 80 mm FOV, giving a resolution of 0.18 mm in all three acquired directions allowing freedom of reconstructed image planes, 50,000 radial projections, UTE/TE2 0.07 ms/2.46 ms (for in-phase fat/water image), TR 9.6 ms, and flip angle 10 . Concentrations in microgram of iron per milliliter of solution (in physiological NaCl) ranging from 12.5 to 200 mg/mL were injected for the in vivo experiments using 50 mL per knee.…”

“…Preliminary reports suggest the potential of MR imaging for noninvasive serial monitoring, for example, in animal models of arthritis (3), with cells labeled ex vivo including immune rejection (4) and similar applications (5-7), and in vivo uptake in inflammation and macrophage tracking (8). Despite the clear visibility of signal loss on the images, this cannot easily be quantified (9,10). Problems include similar areas of hypointense signal that can be created by other structures in the same region, inhomogeneous background signal, and complete saturation of the signalto-noise levels after an initial peak in intensity at very low concentrations.…”