CMR 2005: 9.05: Magnetic labeling and in vivo tracking of embryonic stem cells: efficacy, biological effects, high‐field detection limits and long‐term results

Abstract

Rationale and Objective: Conventional MRI techniques to track ferumoxide-labeled stem cells rely on the detection of signal voids, which often mimic other image artifacts. Several bright marker imaging techniques have been proposed (1,2), but are either poorly suited for in vivo cardiac imaging or have limited utility owing to reduced signalto-noise ratios. Furthermore, these techniques are not compatible with MR device tracking for transcatheter therapeutics. We present here a novel technique, called Inversion-Recovery with ON water resonance suppression (IRON), to perform positive enhancement of magnetic nanoparticles and also allow the visualization of conventional interventional devices such as stents and catheters. Methods: Mesenchymal stem cells (MSCs) were isolated from bone marrow and MR-labeled with 25 mg Fe/mL ferumoxides and 375 ng/L poly-L-lysine for 24 h as previously described (3,4). IRON imaging of six different concentrations of MR-labeled MSCs, oil and coagulated blood was performed on a 1.5 T MR scanner. The IRON pulse sequence consists of: (i) two non-selective-inversion recovery pulses separated by an interval TI to null fat; (ii) a spatial presaturation radiofrequency pulse centered on the water frequency to suppress all signal except the protons locally dephased by field inhomogeneities created by non-diamagnetic objects; and (iii) a turbo spin-echo image acquisition. This results in an image consisting of bright signal from both devices and magnetic nanoparticles while suppressing all of the surrounding tissue including fat. In vivo studies were performed in dogs with and without myocardial infarction and a New Zealand White rabbit subjected to hindlimb ischemia. In one canine study, labeled MSCs ($7Â10 6 MSCs per injection) were injected transmyocardially using a transcatheter approach under MR fluoroscopy to target MSCs to the infarcted myocardium. IRON imaging of MR-labeled MSCs was compared with conventional gradient-echo (GRE) images. Using a roadmap anatomical image, passive catheter tracking was performed using a real-time IRON gradient and spin-echo (GRASE) sequence in another dog for stent deployment. The volume of tissue enhancement with IRON after direct intramuscular MR-labeled MSCs ($7Â10 6 MSCs per injection) in the rabbit hindlimb was compared with intramyocardial delivery in the dog. Results: A high correlation between MR-labeled MSC concentration and volume of signal enhancement was obtained using in vitro IRON imaging ( y ¼ 149x AE 20, R 2 ¼ 0.99) with adequate fat suppression. Expected dipole enhancement of each MSCs concentration and MSC injection sites in the infarcted heart, but not clotted blood, was demonstrated with a 3D IRON sequence. On 2D IRON images, the volume of signal enhancement could be dynamically altered by altering the bandwidth of the on water suppression pulse. However, in all cases, the volume of positive enhancement from direct skeletal intramuscular injections were larger than that from equivalent intramyocardial injections. Successful iliac stainle...