Corticotropin-releasing factor (CRF) is a neuromodulator of brain functions such as learning and anxiety, and is involved in several psychiatric disorders. Targeting CRF binding sites with spatial and temporal resolution by using magnetic resonance imaging (MRI) would greatly facilitate research on the CRF system. Therefore, we synthesized and pharmacologically characterized a CRF analog labeled with gadolinium, the contrast agent most commonly used in MRI. The chelator DOTA was coupled to the N-terminus of human/rat CRF (h/rCRF) under standard solid phase peptide synthesis conditions. The obtained DOTA-h/rCRF was purified and loaded with gadolinium (Gd) in a reaction monitored with mass spectrometry. After purification, Gd-DOTA-h/rCRF was tested for its pharmacological properties using transfected human embryonic kidney (HEK) 293 cells producing either rat CRF receptor (CRFR) 1, mouse CRFR2β or rat CRF binding protein (CRFBP). The affinities of Gd-DOTA-h/rCRF to rat CRFR1 (IC50 = 4.5 nM) and mouse CRFR2β ...

Hypoxia and edema are frequent and serious complications of traumatic brain injury (TBI). Therefore, we examined the effects of hypoxia on edema formation after moderate lateral fluid percussion (LFP) injury using NMR diffusion weighted imaging (DWI). Adult Sprague-Dawley rats were separated into 4 groups: sham uninjured (S), hypoxia alone (H), trauma alone (T), trauma and hypoxia (TH). Rats in Groups T and TH received LFP brain injury, with Groups H and TH undergoing 30 min of severe hypoxia (FiO2 = 0.11) immediately after surgery or TBI (respectively). DWIs were obtained at 2, 4, 24 hours and 1 week postinjury and apparent diffusion coefficient (ADC) maps were constructed. Rats in Groups T and TH showed an early decrease (p<0.001) in ADC values in the ipsilateral cortex 4 hr postinjury, followed one week later by elevated ADCs (p<0.05). No significant differences were seen between T and TH groups in cortex. In contrast, the ipsilateral hippocampus for Group TH showed only increasing ADC values. This hype...

We present a neuroanatomical study of the harbor porpoise (Phocoena phocoena) brain using Magnetic Resonance Imaging (MRI). The specimen is the postmortem brain of a stranded adult harbor porpoise. Magnetic resonance images of the entire brain were acquired in the coronal plane with a 1.5 T Philips NT scanner (Philips Medical System, The Netherlands) at Emory University School of Medicine. Computer-generated 3D reconstructed images were created using the software programs VoxelView and VoxelMath programs (Vital Images, Inc.). The 3D rendered model was then digitally resectioned in orthogonal planes to produce corresponding virtual section series in the horizontal and sagittal planes. Morphometric analyses were conducted using the computer-based program Scion Image. In this poster we present both qualitative and quantitative data on various structures and features of the harbor porpoise brain. This study represents one of a very few studies of the harbor porpoise brain and provides critical data for compara...

The olfactory system is a unique route for uptake and transport of materials to the central nervous system. The purpose of this study is to trace transport of a paramagnetic substance, manganese, in the rat olfactory system using serial magnetic resonance imaging. Sequential magnetic resonance imaging on a 1.5T MR scanner using a rat brain volume coil and 3D SPGR pulse sequence was performed at pre-injection, and 6, 9, 12, 24, 36, and 48 hour post injection of 10 microliter MnCl2 solution via polyethylene catheter into the right nasal cavity in 5 male Sprague Dawley rats under isoflurane anesthesia. Changes in signal intensity were measured by region-of-interest analysis as well as voxel-by-voxel subtraction analysis of post-pre injection images using image coregistration. Signal intensity changes of greater than 1.9 target to muscle ratio were seen progressively in the right olfactory epithelium (post injection), olfactory bulb (< 6 hrs), olfactory tubercle (<9 hrs), piriform cortex (<9 hrs), and entorhin...

In the songbird brain, HVc and its two monosynaptic targets RA and area X are useful models to study brain plasticity. Thus far the volume of these nuclei was determined by histological procedures that obviously make repeated measures impossible. We recently showed that in vivo injection of Mn2+-ions into HVc allows visualizing and accurately delineating RA and area X by Manganese Enhanced-MRI. The present study analyzed the effect of testosterone (T) on the volume of RA and area X and axonal transport dynamics of Mn2+ in female starlings that were implanted with a cannula in the right HVc. Repeated visualization of RA and area X detected a marked volume increase in T-treated birds. The dynamics of axonal transport was altered after T-treatment in the area X, but not in RA. Subsequent analysis of the Mn2+-accumulation based on individual pixels of the MRI images showed an inside-out uptake in RA of both T-treated and controls birds. Mn2+-accumulation was observed in both the medial and lateral parts of are...

Functional magnetic resonance imaging (fMRI) of primary olfactory cortex (POC) has yielded inconsistent results. Odorant-induced POC activity is present at times and absent at others even within the same lab using the same task. Most statistical models used in analysis of fMRI data rely on two assumptions: 1. a monotonic transform from quantity of stimulus to quantity of neural activity, and 2. a linear transform from quantity of neural activity to quantity of MR signal. Whereas the latter has been demonstrated for MR (Boynton et al., 1996), the former has not been demonstrated for POC. Models of temporal encoding, unlike rate-encoding models of olfaction, imply no monotonic transform from quantity of stimulus to quantity of neural activity in POC. Thus, fMRI is potentially invalid as a measure of POC activity under temporal encoding models. To address this we set out to quantify the stimulus intensity-dependence in POC. An olfactometer was used to generate high and low concentrations of the odorants citra...

The good coverage and high resolution afforded by functional magnetic resonance imaging (fMRI) make it an excellent tool for the noninvasive imaging of the human brain. Equally interesting, however, is the use of this technique in animal studies using high magnetic fields. In the latter case, highly

Previous functional neuroimaging studies have not determined cortical areas of selective somatosensory processing of stimulus attributes or location. To address this, we studied 20 subjects trained in two tactile tasks. For both tasks, a set of domes with gratings was used. Gratings were delivered to the immobilized finger. For each trial, a grating was first applied distally with the bars/grooves parallel to the long axis of the finger. Subjects were either required to judge if the grating orientation (GOT) or stimulation site (location task (LOT) changed during a 2nd presentation. Subjects attended to either orientation or location while activations were measured using block design fMRI at 3T. Group performance was very similar for the GOT (74% correct responses) and LOT (74%). Similar activations for both tasks were seen in the primary and secondary somatosensory cortices. The intraparietal sulcus (IPS) was preferentially activated bilaterally in most subjects during the GOT. However, there were signifi...

The capacity to attend to task demands while viewing nontask-related emotional stimuli undergoes profound development during adolescence. However, researchers are only beginning to explore neurobiological correlates of this cognitive process. In the present investigation, 17 adolescents (9-17 years of age) and 17 adults (25-36 years of age) were scanned using event-related fMRI at 3T. Subjects viewed neutral and emotional faces (angry, fearful and happy) passively and also while attending to emotional and physical features. In the initial analysis, three main results emerged. (1) Adolescents showed greater amygdala and prefrontal cortex activation than adults during passive viewing of angry vs. neutral faces. (2) Both adults and adolescents engaged ventral lateral and dorsal prefrontal regions while attending to internal fear state during angry vs neutral face viewing. (3) Greater discriminant activation emerged in adults vs. adolescents within the contrast of internal fear rating to angry faces vs. physic...

Considering the close phylogenetic relationship between humans and chimpanzees, it is of particular interest to characterize the age-related changes of the chimpanzee brain that correspond to key foci of pathologic brain aging in humans such as hippocampus, entorhinal cortex, and basal ganglia. Recently, we reported that, unlike aged humans with neurodegenerative pathology, aged great apes have preserved neuron number and cellular volume in layer II neurons of the entorhinal cortex. In the present study, we measured the volume of the hippocampus, caudate nucleus, and putamen from magnetic resonance images (MRIs) of a cross-sectional age-graded sample of postmortem chimpanzee brains. Volumes of interest (VOIs) were measured from either axial T1 weighted or coronal T2 weighted scans, using MRIcro software. VOI measurements were normalized for whole brain volume. Whole brain, raw VOI, and normalized VOI volumes were not correlated with age. ANOVA found no differences in any VOI between age cohorts (19-27 and ...