Determination of blood circulation times of superparamagnetic iron oxide nanoparticles by T2* relaxometry using ultrashort echo time (UTE) MRI.

Blood circulation is an important determinant of the biodistribution of superparamagnetic iron oxide nanoparticles. Here we present a magnetic resonance imaging (MRI) technique based on the use of ultrafast echo times (UTE) for the noninvasive determination of blood half-lives at high particle concentrations, when conventional pulse sequences fail to produce a useful MR signal. Four differently coated iron oxide nanoparticles were administered intravenously at a dose of 500 µmol Fe/kg bodyweight and UTE images of C57BL/6 mice were acquired on a 1-T ICON scanner (Bruker). T2* relaxometry was done by acquiring UTE images with echo times of 0.1, 0.8 and 1.6 ms. Blood circulation time was then determined by fitting an exponential curve to the time course of the measured relaxation rates. Circulation time was shortest for particles coated with malic acid (t1/2=23 min) and longest for particles coated with tartaric acid (t1/2=63 min). UTE-based T2* relaxometry allows noninvasive determination of blood circulation time and is especially useful when high particle concentrations are present.

Pulmonary blood flow distribution in stage 1 chronic obstructive pulmonary disease.

We investigated the hypothesis that lung blood flow distribution is modified in stage 1 chronic obstructive pulmonary disease (COPD). We compared patients with stage 1 COPD (n = 11) with restrictive patients with comparable blood gases (n = 7), to patients with low cardiac index with normal lungs (n = 11) and to control subjects (n = 11). Distribution of transit time (DTT) was computed by deconvolution from first pass radioactivity curves (albumin (99m)Tc) reconstructed from right and left ventricular regions of interest. Distribution descriptors, mean transit time (p < 0.05), standard deviation (p < 0.001), relative dispersion (p < 0.001), and kurtosis (p < 0.001) differed between groups (ANOVA). Cardiac index was the same in COPD and low CI groups but lower compared with normal subjects (p < 0.05). After normalization for cardiac output, the DTT of patients with COPD remained different from low CI and restrictive patients (p < 0.001). Therefore changes in DTT in patients with COPD compared with patients without COPD could not be explained on the basis of difference in cardiac output. Because P(O(2)), PC(O(2)), and pH were similar in COPD and restrictive groups, difference in distribution could not be explained either on the basis of blood gas data. We conclude that changes in DTT occurs in stage 1 COPD and cannot be explained by hypoxemia, hypercapnia, or acidosis alone but must relate to other structural or regulatory responses.