Validation of an automated punctate mechanical stimuli delivery system designed for fMRI studies in rodents.

Functional magnetic resonance imaging (fMRI) is increasingly being used for animal studies studying the transmission of nociceptive information. Application of noxious mechanical stimuli is widely used for animal and human assessment of pain processing. Any accessory hardware used in animal imaging studies must, however, be sufficiently small to fit in the magnet bore diameter and be non-magnetic. We have developed a system that can apply mechanical stimuli simultaneously with fMRI. This system consists of a standardized instrument to deliver mechanical stimuli (VonFrey monofilament) and a gas-pressured mechanical transducer. These components were integrated with a computer console that controlled the period of stimuli to match acquisition scans. Preliminary experiments demonstrated that the force-stimulus transducer did not influence MRI signal to noise ratio. Mechanical stimulation of the hindpaw significantly increased blood oxygen level dependent (BOLD) signal intensity in several midbrain regions involved in the processing of nociceptive information in the rat (p<0.001, uncorrected for multiple comparisons). This system can be applied to both animal and human imaging studies and has a wide range of applications for studies of nociceptive processing.

Optimisation of T2*-weighted MRI for the detection of small veins in multiple sclerosis at 3 T and 7 T.

T2*-weighted magnetic resonance imaging at 7 T has recently been shown to allow differentiation between white-matter multiple sclerosis lesions and asymptomatic white-matter lesions, by the presence or absence of a detectable central blood vessel. The aim of the present work is to improve the technique by increasing the sensitivity to veins at both 3 T and 7 T, and to assess the benefit of ultra-high-field imaging. Signal-to-noise ratio (SNR) measurements and simulations are used to compare the sensitivity of magnitude T2*-weighted and susceptibility-weighted images for the detection of small veins (<1 pixel in diameter), both with and without the use of gadolinium. The simulations are used to predict the optimal scanning parameters in order to increase the sensitivity to these veins at both field strengths, and to reduce the inherent dependence on vessel orientation. The sensitivities of the sequences at both field strengths are compared, theoretically and experimentally, in order to quantify the benefit of imaging at ultra-high-field. Subjects with multiple sclerosis (MS) are scanned at both field strengths, using the optimised sequence parameters, as well as those used in previously published work, and the optimisation is shown to improve the detection of veins within lesions.

Capsaicin-evoked brain activation and central sensitization in anaesthetised rats: a functional magnetic resonance imaging study.

Functional magnetic resonance imaging (fMRI) of blood oxygen level dependent (BOLD) haemodynamic responses was used to study the effects of the noxious substance capsaicin on whole brain activation in isofluorane anaesthetised rats. Rats (n=8) received intradermal injection of capsaicin (30 microg/5 microl), or topical cream (0.1%) capsaicin and BOLD responses were acquired for up to 120 min. Effects of capsaicin versus placebo cream treatment on the BOLD response to a 15 g mechanical stimulus applied adjacent to the site of cream application were also studied. Both injection and cream application of capsaicin activated brain areas involved in pain processing, including the thalamus and periaqueductal grey (PAG) (p<0.05, corrected for multiple comparisons). Capsaicin also produced increases in BOLD signal intensity in other regions that contribute to pain processing, such as the parabrachial nucleus and superior colliculus. Mechanical stimulation in capsaicin-treated rats, but not placebo-treated rats, induced a significant decrease in BOLD signal intensity in the PAG (p<0.001). These data demonstrate that the noxious substance capsaicin produces brain activation in the midbrain regions and reveals the importance of the PAG in central sensitization.