We are developing fMRI to characterise common homeostatic and reward pathways of drugs and natural regulators of appetite. As a proof of concept, an anorexic dose of the 5-HT2C/1B receptor agonist m-chlorophenylpiperazine (mCPP; 3mg/kg s.c.) was used to compare fMRI with expression of the c-Fos protein. mCPP was injected into satiated male Sprague-Dawley rats, which were then anaesthetised and perfused transcardially 90 min later to allow immunocytochemistry. In a separate experiment, rats underwent fMRI in a 7 Tesla magnet for 70 min under α-chloralose anaesthesia. A T2* weighted gradient echo was used to record brain volumes every 70 s. Results, analysed using SPM99 software, determined brain areas with significant changes in Blood Oxygenation Level Dependent (BOLD) contrast. Both methods detected activity in areas of the limbic system: nucleus accumbens, medial hypothalamus, bed nucleus of the stria terminalis, and thalamus. fMRI detected activation in the pontine nuclei, the hippocampal formation and s...

The rabbit is an ideal animal for fMRI imaging research. It is uniquely tolerant of restraint for prolonged time periods without the need for any anaesthetic to immobilize the animal. The visual pathways and central mechanisms of both pattern and movement vision are well explored. In addition the associative conditioning of the rabbit nictitating membrane has long been a major animal model for studying neural mechanisms of associative learning. The purpose of the present study is to determine the concordance between MRI assessment of the extent of experimentally induced brain lesions with postmortem histological reconstruction of the lesions. Using sterile procedure discrete sections of the corpus callosum were made in the rabbit brain. Assessment of tissue damage was undertaken both after 1 hour and 72 hours following surgery. Magnetic field images (6 Tesla) of lesion damage are described and compared with detailed histological reconstruction for both fiber and cellular damage.

The purpose of this study was to detect the uptake and distribution of oligodeoxynucleotides (ODN) delivered to the brain using high-resolution magnetic resonance imaging (MRI) in live animals. We used a phosphorothioated ODN (s-ODN) of 26-mer, which interfered the expression of Fos/AP-1 activities after stroke of rats [J. Neuroscience 19:2784; Brain Res 832:112-117]. Monocrystalline iron oxide nanoparticles (MION) were covalently bound to the s-ODN as a novel MR contrast agent. MION is a MR T2 agent, which reduces the signal intensity of its surrounding medium in the T2*-weighted MR images. We investigated two groups of animals in this study: control animals with MION only and animals with the novel conjugate, MION-s-ODN (2 ug MION in 2 ul artificial CSF per animal). MION or MION-s-ODN was delivered to the brain of C57bB6 mice (20 gm) via intracerrebroventricular route. Immediately following infusion, we observed a significant, bilateral signal reduction within the ventricular space of all animals in the ...

We describe a frameless stereotaxic method for guiding recording electrode position. This involves two steps; Stereotaxic mapping of the brain to position a recording chamber, and subsequent stereotaxic mapping of the brain beneath the chamber expressed in chamber coordinates. Prior to surgery the animal undergoes T1 weighted 3D MR imaging, providing an anatomical dataset of 0.7mm resolution. The monkey is anesthetized for the MRI using a cocktail of ketamine, xylazine and atropine. Only light anesthesia is needed as the method requires no rigid stereotaxic fixation. Images are post-processed using AFNI software. The 3D image is rotated into the standard stereotaxic plane using skull/brain anatomy, and stereotaxic zero is set in the midline at the extended horizontal convergence of the external auditory meatii (to coincide with the surgical stereotaxic unit). This MRI is used to determine the optimal center and angle for surgically placing the recording chamber. Following attachment of the chamber the monk...

In order to understand the kinematics of the musculature controlling feeding in the marine mollusk Aplysia californica, we have developed a series of increasingly realistic kinematic models of the feeding apparatus, the buccal mass (Drushel et al., JEB, 1998; Chiel et al., Soc. Neurosci. Abstr., 1998, 1999). Using high spatial resolution MRI scans of freshly dissected buccal masses, a realistic external shape of the radula/odontophore at rest has been determined, which is approximated by modified ellipsoid octants. The surface of the radula is approximated by two planes that intersect the volume of the odontophore. By extracting parameters from high temporal resolution MRI taken of the buccal mass during swallowing movements in intact animals, it is possible to generate realistic shapes and positions for the radula/odontophore during the entire swallowing cycle, subject to the biological constraints that the total surface of the radula and the total volume of the odontophore are kept constant. To validate ...

Computer algorithms exist to remove non-brain tissue from structural MRIs. Each algorithm possesses strengths and weaknesses dependent on scanner, protocol, and subjects, and produces different results for the same data. Simultaneous use of multiple algorithms with a combination step builds on the strengths of the individual extractors yielding a meta-algorithm that produces more accurate and robust results. The meta-algorithm incorporates information from four different extractors, BET (Smith, 2002), BSE (Shattuck et al., 2001), 3dIntracranial (in AFNI; Ward, 1999), and Watershed (in FreeSurfer; Segonne et al., 2003), and a registration procedure, FLIRT (Jenkinson et al., 2002). A trainer program analyzes results from the four extractors aligned to an atlas space against manually traced gold-standards of brain. For each region in the atlas space it selects a four input boolean function that produces the best results across the gold-standards. It outputs a combination-key that stores the proper combination...

In the perinatal period, human brain growth is most rapid and the parameters of growth are greatly sensitive to deleterious influences upon brain development. Standard MRI-based morphometric techniques are of limited application at this age because the perinatal brain is minimally myelinated and lack the marked differences in tissue contrast upon which standard approaches depend. The goal of the present study is to develop an accurate, reliable and reproducible method for segmentation and volumetric analysis of the minimally myelinated brains in the range of 34 to 42 weeks gestational age. The emphasis is placed upon the forebrain where highly reliable criteria allow segmentation of the external contour, the separate boundaries of the hippocampus and amygdala and en bloc basal nuclear structures including caudate, diencephalon, striatum and pallidum. It is intended that a series of perinatal brains segmented in terms of these boundaries will serve as a training set for the automated segmentation algorithm,...

Cycad (Cycas micronesica K.D. Hill) feeding has been shown to induce neurodegeneration in vivo that mimics the progressive neurological disease, ALS-PDC (Wilson et al., 2002). Previously, specific cortical and subcortical cell loss was measured with stained 2D sections. In this study, MRI images were used to examine neurodegeneration in 3D. Mice were fed washed cycad as part of their normal diet for 2 months and showed progressive motor and cognitive behavioral deficits resembling human ALS-PDC. Animals were perfused and CNS tissue was scanned using a 750MHZ MRI with a 17.6T magnet. T2* and diffusion tensor scans were conducted on both spinal cord and brain samples. MRI data files were then analyzed using Amira 3.0 software to segment out areas of interest and measure volumes and cortical thickness. Resolution of the scans was ~40µm. Cycad-fed mice showed significantly decreased substantia nigra, striatum, and olfactory bulb (granular layer) volumes. Cycad-fed mice that received stem cell injections displa...

The main goal of this MRI study was to determine if longitudinal structural changes occurring in ALS could be mapped using high-resolution tensor-based serial morphometry. Eleven ALS Patients (54 ±12yrs), 5 presenting with upper-limb symptoms and 6 with lower-limb symptoms underwent two MRI scans (coronal 3D T1 MPRAGE with 1x1 mm in-plane resolution) with intervals of 9-18 months. Each subject’s images were co-registered, small-scale changes between longitudinal MRIs were captured and local tissue volume changes over time were mapped. To allow comparisons between groups, each individual was registered to a common reference MRI. Both the upper and lower limb group showed atrophy in different regions of motor cortex. Upper limb patients had tissue loss in lateral motor cortex while patients with lower limb onset had tissue loss in medial motor cortex. This distribution is consistent with the expected anatomical distribution of pathology in ALS. In addition, both groups had bilateral frontal lobe atrophy cons...

Based on its neuronal uptake and axonal transport in analogy to calcium ions, manganese (Mn2+) has been introduced as a paramagnetic contrast agent for neuroaxonal tract tracing using magnetic resonance imaging (MRI). Extending previous work on murine brain in situ, this study demonstrates mapping of the visual pathway in living rats (n=6) at 2.35 T (Bruker, DBX). Multiple follow-up examinations at high spatial resolution (195 x 195 x 125μm3) were performed with use of T1-weighted 3D gradient-echo MRI (TR/TE=15/4.2ms, flip angle 25°) at 8h, 24h, 48h, and 72h after intraocular Mn2+ injection (0.1μl of 1M aqueous MnCl2). Best results were obtained at 24h post-injection revealing a continuous pattern of anterograde labeling from the retina, optic nerve, and chiasm to the contralateral optic tract, the dorsal and ventral lateral geniculate nucleus, the superior colliculus and its brachium, the olivary pretectal nucleus, the nucleus of the optic tract, and the suprachiasmatic nucleus. The approach is expected t...