The aim of this study was to assess a possible association between breast malignancy and ipsilateral higher vascularity on gadolinium-enhanced MR angiography. One hundred six patients were examined by dynamic gadolinium-enhanced 3D MR imaging. Magnetic resonance angiographic views were generated by image subtraction and maximum intensity projection. The study included 85 patients with unilateral malignant breast neoplasms and 21 with unilateral benign lesions. Three blinded readers independently reviewed the MR angiograms after masking the lesions and the corresponding contralateral sites. The readers were asked to determine whether vascularity was higher on the right side, higher on the left side, or equal on both sides. The results were analyzed by the Kappa statistic and Pearson's chi-square test. The blood vessels of the breasts were clearly seen in all cases. There was good agreement among the observers (kappa > 0.54) in assessing vascularity on both sides. Breasts harboring malignant neoplasms were found to have a higher vascularity than the contralateral breasts (p < 0.005). This sign of malignancy had a sensitivity of 76.5%, a specificity of 57%, and an accuracy of 72.6%. Blood vessels of the breast can be depicted by MR angiography. Unilateral malignant neoplasms are associated with a higher ipsilateral vascularity. In conjunction with other indications of malignancy on gadolinium-enhanced MR images, a higher ipsilateral vascularity may serve as an additional sign of malignancy.
Fiber type distribution within a skeletal muscle, i.e. the quantification of the relative amount of type 1 (slow-twitching) and type 2 (fast-twitching) muscle fibers, is of great interest for the monitoring of the effects of training or the treatment of muscle diseases. The purpose of this study was to determine the feasibility of diffusion tensor imaging (DTI) as a tool for noninvasive fiber type quantification in human skeletal muscle. The right calves of 12 healthy volunteers were examined using DTI at 1.5 T. Standard DTI parameters, including fractional anisotropy (FA), and mean, radial and parallel diffusivity (MD, RD and PD, respectively), were determined in the soleus muscle. Fiber type proportion and mean fiber diameter within the soleus muscle were quantified from tissue specimens obtained via a fine needle biopsy. Linear regression analysis tested for associations between DTI and biopsy results. FA values were correlated significantly with fiber type proportion, such that higher FA values indicated a higher proportion of type 1 fibers (R(2) = 0.5, p = 0.01). This was based on lower diffusivity perpendicular to the main axis of the fiber in subjects with a higher type 1 fiber proportion (RD: R(2) = 0.52, p = 0.008). MD was also correlated with the proportion of type 1 fibers (R(2) = 0.37, p = 0.037), whereas PD showed no significant correlation. DTI is a promising method for the noninvasive estimation of fiber type proportion in skeletal muscle. This technique may be used to monitor training effects or may be further developed as a biomarker in certain muscle diseases.
Magnetic resonance imaging (MRI) of a target in vivo depends on the surface, size, and particle relaxivity of the target-specific nanoparticles for MRI. Here a new method for decorating very small iron oxide particles (VSOPs) with target-specific ligands is described. The method is based on the electrostatic attraction of the strongly positively charged peptide protamine to the anionic citrate shell of the electrostatically stabilized VSOPs. The protamine coat allows linkage chemistry and chimera technology to functionalize VSOPs or other negative charged surfaces with biologics. Annexin A5 (anxA5)-VSOP utilizing thiol chemistry was generated to couple biologically active anxA5 to VSOPs for in vivo MRI of apoptosis. Annexin A5-VSOP comprises five anxA5 molecules per iron oxide nanoparticle with a high R2 particle relaxivity of 180 000 mM(-1) s(-1) yet small hydrodynamic diameter of only 14.7+/-2.9 nm beneficial for in vivo MRI of extravascular targets.
Extracellular vesicles (EV) function as messengers between endothelial cells (EC) and vascular smooth muscle cells (VSMC). Since chronic kidney disease (CKD) increases the risk for vascular calcifications, we investigated whether EV derived from uraemic milieu‐stimulated EC and derived from uraemic rats impact the osteogenic transdifferentiation/calcification of VSMC. For that purpose, human EC were treated with urea and indoxyl sulphate or left untreated. Experimental uraemia in rats was induced by adenine feeding. ‘Uraemic’ and control EV (EVUR; EVCTRL) were isolated from supernatants and plasma by using an exosome isolation reagent. Rat VSMC were treated with a pro‐calcifying medium (CM) with or without EV supplementation. Gene expressions, miRNA contents and protein expressions were determined by qPCR and Western blots, respectively. Calcifications were determined by colorimetric assays. Delivery of miRNA inhibitors/mimics to EV and siRNA to VSMC was achieved via transfection. EVCTRL and EVUR differed in size and miRNA contents. Contrary to EVCTRL, EC‐ and plasma‐derived EVUR significantly increased the pro‐calcifying effects of CM, including altered gene expressions of osterix, runx2, osteocalcin and SM22α. Further, EVUR enhanced the protein expression of the phosphate transporter PiT‐1 in VSMC and induced a phosphorylation of AKT and ERK. Knock down of PiT‐1 and individual inhibition of AKT and ERK signalling in VSMC blocked the pro‐calcifying effects of EVUR. Similar effects were achieved by inhibition of miR‐221/‐222 and mimicking of miR‐143/‐145 in EVUR. In conclusion, EVUR might represent an additional puzzle piece of the complex pathophysiology of vascular calcifications in CKD.
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