Improved cerebral blood flow and hippocampal blood flow in stroke-free patients after catheter ablation of atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is a risk factor for reduced cerebral blood flow (CBF) and cognitive dysfunction, even in stroke-free patients. We aimed to test the hypothesis that CBF and hippocampal blood flow (HBF), measured with arterial spin labeling magnetic resonance imaging (MRI), improve after catheter ablation of AF to achieve sinus rhythm (SR). METHODS: A total of 84 stroke-free patients (63.1 ± 9.1 years; paroxysmal AF, n = 50; non-paroxysmal AF, n = 34) undergoing AF catheter ablation were included. MRI studies were done before, 3 months, and 12 months after the procedure with CBF and HBF measurements. RESULTS: Baseline CBF and HBF values in 50 paroxysmal AF patients were used as controls. Baseline CBF was higher in patients with paroxysmal AF than with non-paroxysmal AF (100 ± 32% vs. 86 ± 28%, p = .04). Patients with non-paroxysmal AF had increased CBF 3 months after AF ablation (86 ± 28% to 99 ± 34%, p = .03). Differences in CBF and HBF were greater in the group with AF restored to SR (p < .01). Both CBF and HBF levels at 12 months were unchanged from the 3 months level. Successful rhythm control by catheter ablation was an independent predictor of an increase in CBF > 17.5%. The Mini-Mental State Examination score improved after ablation (p = .02). CONCLUSION: SR restoration with catheter ablation was associated with improved CBF and HBF at 3 months, maintenance of blood flow, and improved cognitive function at 12 months.

In vivo visualization of redox status by high-resolution whole body magnetic resonance imaging using nitroxide radicals.

Various diseases are known to be associated with an imbalance of the redox state, but in vivo detection of free radicals is difficult. The purpose of this study is to establish a method for in vivo visualization of redox status by high-resolution whole-body MRI using nitroxide radicals. A redox-sensitive nitroxide probe, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL), was administered to rats intravenously, and in vivo T1-weighted MRI was performed to virtually visualize the redox status of various organs. In experiments using phantoms, a linear relationship between the MRI signal and the carbamoyl-PROXYL concentration persisted up to 80 mM. Among the phantoms, a sample containing 1 mM carbamoyl-PROXYL was readily identifiable. After intravenous injection of carbamoyl-PROXYL, whole-body T1-weighted MRI of the rat provided clear images with good spatial and temporal resolution. The signal intensities of four selected organs (heart, liver, kidney, and intestine) were analyzed quantitatively. The carbamoyl-PROXYL signal peaked and gradually declined due to reduction after intravenous injection. Among the four organs, the organ-specific reduction rate of carbamoyl-PROXYL was highest in the heart, followed by (in order) the liver, kidney, and intestine, and statistical analysis showed that the inter-organ differences were significant. In conclusion, T1-weighted carbamoyl-PROXYL-enhanced MRI provides excellent spatial and temporal imaging of carbamoyl-PROXYL distribution. Furthermore, it provides important functional information pertaining to blood flow and tissue redox activity in individual organs. MRI in combination with carbamoyl-PROXYL has potential clinical application for evaluation of redox activity in whole organs.

Oxidative stress evaluation of skeletal muscle in ischemia-reperfusion injury using enhanced magnetic resonance imaging.

Acute extremity arterial occlusion requires prompt revascularization. Delayed revascularization induces ischemia-reperfusion injury in the skeletal muscle. Organ injury-induced oxidative stress is widely reported, and oxidative stress is heavily involved in ischemia-reperfusion injury. This study aimed to evaluate oxidative stress in ischemia-reperfusion rat models using 3-carbamoyl PROXYL enhanced magnetic resonance imaging (3-CP enhanced MRI). Ischemia-reperfusion injury was induced through clamping the right femoral artery in rats, with a 4-h ischemia time in all experiments. 3-CP enhanced MRI was performed to evaluate oxidative stress, and the rats were divided into 3 reperfusion time groups: 0.5, 2, and 24 h. Signal intensity was evaluated using 3-CP enhanced MRI and compared in the ischemia-reperfusion and intact limbs in the same rat. Furthermore, the effect of edaravone (radical scavenger) was evaluated in the 4-h ischemia-24-h reperfusion injury rat model. The signal intensity of the ischemia-reperfusion limb was significantly stronger than that of the intact limb, suggesting that oxidative stress was induced in the ischemia-reperfusion muscle. Edaravone administration reduced the oxidative stress in the ischemia-reperfusion limb. The signal intensity of the ischemia-reperfusion limb was stronger than that of the intact limb, presumably reflecting the oxidative stress in the former. 3-CP MRI examination shows promise for effective assessment of oxidative stress and may facilitate early diagnosis of ischemia-reperfusion injury.

In vivo analysis of redox status in organs - from bench to bedside.

Reactive oxygen species (ROS) such as superoxide, hydroxyl radical, and hydrogen peroxide play an important role in the maintenance of life. However, production of excessive ROS and/or deficiency of the antioxidant system lead to oxidative stress and cause a variety of diseases. In the present study, we used electron spin resonance (ESR) to detect ROS in vivo to clarify its roles in redox dynamics and organ damage. However, the limited permeability of microwaves and low anatomic resolution of ESR equipment made it difficult to apply clinically. Nitroxide is widely used as a sensitive redox sensor for in vivo ESR analysis. The unpaired electrons of nitroxide are known to cause the T1 relaxation time-shortening effect of water protons, creating magnetic resonance imaging (MRI) effects. The remarkable development of MRI has facilitated the spatiotemporal analysis of nitroxide, which was previously impossible. In a rat model, we have been able to image and analyze the process of nitroxide reduction using MRI. MRI using nitroxide as a contrast medium is considered to be clinically applicable for evaluation of organ redox, imaging of ROS (which cause organ damage), and evaluation of therapeutic effects. In this review, we describe current advances in the analysis of in vivo redox capacity in animals using ESR and MRI equipment. We consider that redox evaluation using MRI can contribute to advances in clinical medicine.