Cerebral blood flow modulation by transcutaneous cranial electrical stimulation with Limoge's current.

OBJECTIVES: Transcutaneous cranial electrical stimulation (TCES) delivers a high-frequency (166 kHz) pulsed biphasic balanced current with a pulse repetition frequency of 100 Hz with 40% duty cycle through a negative electrode and two positive electrodes over the skull. TCES has a proven ability to potentiate anesthesia and analgesia, although the physiological mechanisms of this effect remain unclear. We hypothesized that the mechanism is a modulation of CBF in the central endogenous opioid system. This study aimed at determining the effects of TCES on CBF to elucidate its physiological mechanism. METHODS: Thirty-six healthy volunteers were randomly assigned to active or placebo TCES, and all assessments were double blind. TCES was performed using the Anesthelec™ device. In the stimulated group, an active cable was used, and in the control group (sham), the cable was inactive. CBF was measured by XeCT™ before and after two hours of TCES. RESULTS: Globally, CBF was unchanged by TCES. However, locally, TCES induced a significant CBF decrease in the brainstem and thalamus, which are structures involved in pain and anxiety (TCES and control CBF decrease were 18.5 and 11.9 mL/100g brain tissue/min, respectively). CONCLUSION: TCES can modulate local CBF but it has no effect on overall CBF. [Clinical Trials. gov number: NCT00273663].

MR imaging of relapsing multiple sclerosis patients using ultra-small-particle iron oxide and compared with gadolinium.

BACKGROUND AND PURPOSE: Inflammatory multiple sclerosis (MS) lesions are characterized by microglia activation and infiltration of T cells, B cells, and macrophages across the blood-brain barrier (BBB). In the experimental autoimmune encephalomyelitis (EAE) rat model of MS, previous MR imaging investigations with a new contrast agent ultra-small-particle iron oxide (USPIO) that accumulates in phagocytic cells revealed in vivo the presence of macrophage brain infiltration. The goal of this study was to characterize MS lesions with the use of this contrast agent. METHODS: A prospective MR imaging study of 10 patients with MS in acute relapses was achieved by using USPIO and gadolinium. RESULTS: Twenty-four hours after USPIO injection, 33 acute MS lesions in 9 patients showed USPIO uptake. Lesions were seen as high signal intensities on T1-weighted images and low signal intensities on T2-weighted images. Gadolinium enhancement was seen in 31 of these lesions in 7 patients. These 7 patients presented 24 gadolinium-enhanced lesions that did not enhance with USPIO. Two patients showed USPIO-enhanced lesions but no gadolinium-enhanced lesions. CONCLUSION: Taken together with earlier findings obtained in experimental models or in human stroke, the visualization of macrophage activity in vivo with USPIO characterize a distinct cellular and inflammatory event of the dynamic process of MS lesion formation. The macrophage activity information obtained with USPIO is distinct and complementary to the increased BBB permeability seen with gadolinium.

Dose and scanning delay using USPIO for central nervous system macrophage imaging.

RATIONALE AND OBJECTIVES: In experimental allergic encephalomyelitis (EAE), central nervous system (CNS) macrophage imaging is achievable by MRI using AMI-227 an ultra-small particle iron oxide contrast agent at a dose of 300 micromol/kg Fe. The objective was to test the feasibility at the human recommended dose of 45 micromol/kg Fe. METHODS: Two groups of EAE rats were tested with AMI-227 using 45 and 300 micromol/kg Fe respectively. Following i.v. injection of AMI-227, they were scanned after a delay of 4-6 and 20-24 h. RESULTS: With a high dose of AMI-227, all animals showed low signal intensity related to iron-loaded macrophages in the CNS. At low dose no abnormalities were found in the CNS. Furthermore, a delay of 4-6 h failed to demonstrate abnormalities even at high dose. CONCLUSIONS: Dose, scanning delay after administration and blood half-life are major parameters for T2* CNS macrophage imaging.