Using iron oxide nanoparticles to diagnose CNS inflammatory diseases and PCNSL.

OBJECTIVE: The study goal was to assess the benefits and potential limitations in the use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles in the MRI diagnosis of CNS inflammatory diseases and primary CNS lymphoma. METHODS: Twenty patients with presumptive or known CNS lesions underwent MRI study. Eighteen patients received both gadolinium-based contrast agents (GBCAs) and 1 of 2 USPIO contrast agents (ferumoxytol and ferumoxtran-10) 24 hours apart, which allowed direct comparative analysis. The remaining 2 patients had only USPIO-enhanced MRI because of a renal contraindication to GBCA. Conventional T1- and T2-weighted MRI were acquired before and after contrast administration in all patients, and perfusion MRI for relative cerebral blood volume (rCBV) assessment was obtained in all 9 patients receiving ferumoxytol. RESULTS: USPIO-enhanced MRI showed an equal number of enhancing brain lesions in 9 of 18 patients (50%), more enhancing lesions in 2 of 18 patients (11%), and fewer enhancing lesions in 3 of 18 patients (17%) compared with GBCA-enhanced MRI. Four of 18 patients (22%) showed no MRI enhancement. Dynamic susceptibility-weighted contrast-enhanced perfusion MRI using ferumoxytol showed low rCBV (ratio <1.0) in 3 cases of demyelination or inflammation, modestly elevated rCBV in 5 cases of CNS lymphoma or lymphoproliferative disorder (range: 1.3-4.1), and no measurable disease in one case. CONCLUSIONS: This study showed that USPIO-enhanced brain MRI can be useful in the diagnosis of CNS inflammatory disorders and lymphoma, and is also useful for patients with renal compromise at risk of nephrogenic systemic fibrosis who are unable to receive GBCA.

Fetuin-A serum levels in patients with aortic aneurysms of Marfan syndrome and atherosclerosis.

BACKGROUND: Fetuin-A is a glycoprotein that inhibits extraosseous and vascular calcification. Its serum level is lower in patients with atherosclerosis compared with healthy controls, but its role is unknown in aneurysmal diseases. The aim of our study was to investigate the association of serum fetuin-A levels with aortic aneurysms of different aetiology: Marfan syndrome and atherosclerosis. MATERIAL AND METHODS: In a single centre cross-sectional observational study, 105 patients (30 with atherosclerotic aortic aneurysm, 15 with Marfan syndrome, 30 with peripheral arterial disease and 30 healthy controls) were examined; sera were analysed for fetuin-A, standard markers of possible inflammation, lipid profile, kidney and hepatic disease and diabetes. Systemic atherosclerosis was assessed by carotid intima-media thickness (IMT) measurement and arterial calcification score of cardiac valves, carotids, aorta and femoral arteries determined by ultrasound. RESULTS: Serum fetuin-A levels (median and IQR) were significantly lower in the atherosclerotic aneurysm cohort than in patients with Marfan syndrome: 708 µg mL⁻¹ (612-780) and 756 µg mL⁻¹ (708-816), respectively, (P = 0·0428). Fetuin-A levels were 754 µg mL⁻¹ (713-777) in the control group and 654 µg mL⁻¹ (600-756) in patients with peripheral arterial disease. Mean and maximum IMT, ACS values and homocysteine levels were significantly higher in patients with atherosclerosis: P < 0·0001, P < 0·0001, P < 0·0001 and P = 0·0034, respectively. There was no significant difference between aneurysm groups analysing the results of lipid profile and acute-phase markers. CONCLUSIONS: The significantly lower serum level of fetuin-A in the atherosclerotic aneurysm group supports the protective role of fetuin-A in the evolution of arterial calcification.

Serum level of soluble Hsp70 is associated with vascular calcification.

It has been previously reported that serum levels of 70-kDa heat shock protein (Hsp70) are elevated in peripheral artery disease. The aim of the present study was to examine whether increased serum Hsp70 levels are related to the extent of arterial calcification and standard laboratory parameters of patients with peripheral artery disease, as well as to markers of inflammation (C-reactive protein), atherosclerosis (homocysteine), and calcification (fetuin-a). One hundred eighty chronic atherosclerotic patients with significant carotid stenosis and/or lower extremity vascular disease were enrolled in this cross-sectional study. Systemic atherosclerosis and calcification was assessed by ultrasound (carotid intima-media thickness (IMT), presence of calcification at the abdominal aorta, carotid and femoral bifurcations, and aortic and mitral cardiac valves). Standard serum markers of inflammation, diabetes, renal function, ankle-brachial indexes, and traditional risk factors for atherosclerosis were noted. Serum Hsp70 levels were measured with enzyme-linked immunosorbent assay. Standard laboratory parameters (clinical chemistry), C-reactive protein (CRP), and homocysteine levels were determined by an autoanalyzer using the manufacturer's kits. Fetuin-a levels were measured by radial immunodiffusion. Patients' median age was 64 (57-71) years, 69% were men, and 34.5% had diabetes. Serum heat shock protein 70 levels were significantly higher in patients with more severe arterial calcification (p < 0.02) and showed significant positive correlations with serum bilirubin (r = 0.23, p = 0.002) and homocysteine levels (r = 0.18, p = 0.02). Serum Hsp70 did not correlate with body mass index, IMT, CRP, or fetuin-a levels in this cohort. Logistic regression analysis confirmed the association between sHsp70 and calcification score (OR, 2.189; CI, 1.156-4.144, p = 0.016) and this correlation remained significant (OR, 2.264; CI, 1.021-5.020, p = 0.044) after the adjustment for age, sex, eGFR, smoking, CRP, and homocysteine levels. Our data show that serum Hsp70 levels correlate with the severity of atherosclerosis in patients with carotid artery disease and chronic lower limb ischemia. These data support a putative role for plasma Hsp70 in the development of arterial calcification. Nevertheless, further studies are required to investigate the usefulness of circulating Hsp70 level as a marker of atherosclerotic calcification.