Objectives – We used high resolution MRI together with an effective magnetic labelling to asses the detection limit, localisation, and migration of transplanted embryonic stem cells (ESC) in a rat model of PD. Additionally the influence of the magnetic label on the biology of the cells was investigated. Materials and Methods - ESC were magnetically labelled in vitro with Very Small Super-Paramagnetic Iron-Oxide-Particles (VSOP). The level of oxidative stress was detected by measuring the level of malonyldialdehyde (MDA). Minimal numbers of cells were transplanted into the striatum of healthy rats and MRI at 17.5 T was conducted. MRI at 7T was performed after transplantation of 1 × 105 magnetically labelled cells into the striatum of 6-OHDA lesioned rats. Results - Incubation of ESC with VSOP leads to a highly significant uptake of iron. However the incubation of cells with iron-oxide-particles also results in a transient augmentation of oxidative stress. The MR detection limit in vivo at 17.5 T ranges belo...

Songbirds share with humans the capacity to produce learned vocalizations (song). The neural substrate for song learning and production, the song control system (SCS), is a bilateral circuit of distinct, strongly ipsilaterally interconnected brain regions which displays a remarkable neuroplasticity. After years of bird sacrifice to study the SCS, we recently (Van der Linden et al., 2002) visualized two major song control nuclei, nucleus robustus arcopalii (RA) and X repeatedly in a living songbird using Manganese Enhanced Magnetic Resonance Imaging (MEMRI). It was our aim to extend this accomplishment and visualize the entire SCS in living songbirds taking advantage of the transsynaptic paramagnetic tract tracing capacities of manganese. To that end we stereotactically injected very small volumes (10 nl) of MnCl2 (minimizing possible neurotoxicity) into HVC of the right and into MAN (nucleus magnocellularis nidopalli anterioris) of the left hemisphere, and monitored the manganese tracing between ipsilatera...

Albinism causes foveal hypoplasia and an abnormally large number of fibres from temporal retina to cross the chiasmatic midline. Previous MRI work (Schmitz et al 2003 IOVS, 44 16-21) has indicated that the dimensions of the optic chiasm are abnormal in human subjects with albinism. The same subjects also showed a narrowing of the optic nerves and tracts and an increased angle between the nerves and tracts. Thus, abnormal crossing of visual fibres and reduced foveal cell numbers appear to have an effect on the gross anatomy of the optic chiasm. We have made a series of anatomical measurements of the optic chiasm, optic nerves and tracts based on T1-weighted (1x0.98x0.98mm) structural MRI scans of 20 control subjects (mean age, 34±11) and 19 subjects with albinism (mean age, 33±11). Similar to the previous study, we found that the dimensions of the chiasm were different for the two groups (albino width=9.3±1.0mm, control width=11.5±1.9mm , albino height=3.7±0.9mm, control height=3.4±0.7mm), but this only rea...

Introduction: Regional correlations in the low frequency oscillations of the BOLD signal in the MRI time series are of considerable interest. While their neural origins are still not well understood it is believed that those correlations provide a new insights into the functional connectivity of the human brain. Correlations observed in steady states series of MRI images seem to connect distant but functionally connected regions of the brain. They have been shown to be modified by activation conditions. The origin of those correlations is not well understood and their neuronal origin has not yet been definitively proven. The authors believe that they are caused by vasomotion (low frequency oscillations in the blood flow) that is affected by neuronal connections between distant but functionally connected regions of the brain. Methods: 5 normal control subjects were scanned in two separate sessions. Each study session contained localizer runs that interleaved blocks of working task with control task. These b...

We combined event-related functional magnetic resonance imaging (fMRI) with olfactory classical conditioning to differentiate the neural responses evoked during appetitive and aversive olfactory learning. Three neutral faces [the conditioned stimuli (CS+)] were repetitively paired with pleasant, neutral, or unpleasant odors [the unconditioned stimuli (UCS)] in a partial reinforcement schedule. A fourth face was never paired to odor [the nonconditioned stimulus (CS−)]. Learning-related neural activity, comparing unpaired (face only) CS+ stimuli with CS−, showed valence-independent activations in rostral and caudal orbitofrontal cortex (OFC). Medial OFC responded to the appetitive (app) CS+, whereas lateral OFC responded to the aversive (av) CS+. Within nucleus accumbens, neural responses showed divergent activation profiles that increased with time in response to the appCS+ but decreased in response to the avCS+. In posterior amygdala, responses were elicited by the appCS+, which habituated over time. In te...

Plexiform neurofibromas in patients with neurofibromatosis type I (NF1) typically involve deep or named nerves, can become very large, may cause serious functional impairment and have a risk of malignant progression. In developing an animal model to study plexiform neurofibromas, we have shown that human NF1 neurofibrosarcoma-derived Schwann cells (SC) can be successfully xenografted into the sciatic nerves of scid mice. The histogenesis of engrafted neurofibrosarcoma SC was consistent with that of established human plexiform neurofibromas. The tumors invaded and degenerated the host nerve structure and proliferated in a slow, sustained manner without apparent malignancy. In addition, we observed angiogenic markers in xenografted nerves. We performed MRI to study the formation and progression of these tumors in our model. Using a 17.6 tesla, 89mm bore magnet we performed H-1 MRI at 750MHz on excised, fixed xenografted mouse sciatic nerves. We then compared the T1 weighted images to immunostaining of the sa...

Event-related functional magnetic resonance imaging was used to measure blood oxygenation level-dependent responses in 13 young healthy human volunteers during performance of a probabilistic reversal-learning task. The task allowed the separate investigation of the relearning of stimulus–reward associations and the reception of negative feedback. Significant signal change in the right ventrolateral prefrontal cortex was demonstrated on trials when subjects stopped responding to the previously relevant stimulus and shifted responding to the newly relevant stimulus. Significant signal change in the region of the ventral striatum was also observed on such reversal errors, from a region of interest analysis. The ventrolateral prefrontal cortex and ventral striatum were not significantly activated by the other, preceding reversal errors, or when subjects received negative feedback for correct responses. Moreover, the response on the final reversal error, before shifting, was not modulated by the number of prece...

The primary somatosensory cortex (SI) is widely appreciated for its somatotopic organization of responses to innocuous mechanical stimuli; however, little is known regarding the possible organization of SI responses to noxious stimulation. This within-subject fMRI study compares the spatial distribution of SI responses to innocuous and noxious stimuli presented to the fingers during psychophysical discrimination tasks. Functional MRI data were recorded during 2 separate sessions–one involving innocuous and noxious thermal stimuli (44.0°& 53.0°C) applied to digits 1 and 5, and another in which innocuous vibrotactile stimuli (75, 100, and 125Hz) were applied to the same digits. Initial experiments demonstrate significant activation in SI for both noxious thermal and innocuous vibrotactile stimuli (p< 0.0001). Comparison of data within experimental runs demonstrates significant spatial separation of SI responses evoked by stimulation of digits 1 and 5 for both innocuous vibrotactile (X²; p< 0.0001) and noxiou...

It has previously been shown that Mn2+ is taken up through Ca2+ channels and can be transported along axons. Because Mn2+ ion is also paramagnetic, these combined properties of Mn2+ allow for the use of the ion as an effective MRI detectable, neuronal tract tracer. A previous study has demonstrated Mn2+ tract tracing along the olfactory and visual pathways in live mice. Whereas the previous study traced from sensory pathways leading into the brain, the purpose of the present study was to delineate tract tracings from focal points located within the brain. Nanoliter injections of 5 mM MnCl2 into either the striatum or the amygdala demonstrated contrast enhancement along the correct neuronal circuitry. Furthermore, enhancement of homotopic connections was observed in both cases. In the amygdala tracings, a total of six synapses was traversed as evidenced by positive contrast enhancement due to Mn2+ accumulation (figure). Ten days post injection, the Mn2+ appeared to wash out as enhancement within the brain w...

A characteristic pattern of behavioral and physiological effects is produced by marijuana and its principal psychoactive component, THC, in humans. However, THC’s sites of action in the human brain and their relationships to the drug’s actions are not well described. We have now studied in frequent marijuana users, the effects of two doses of THC (1 and 3 mg iv over 1 min) that produce effects similar to those seen with marijuana use in a social situation, on regional brain activity using BOLD fMRI. The subjects reported that the intensity of the “high” produced by the 3 mg dose was twice that of the lower dose (8/10 vs. 4.5/10). A modest dose-related tachycardia was also observed.Both increases and decreases in brain activity as measured by BOLD fMRI were seen in discrete brain regions. The 3 mg dose of THC produced time-related decreases in fMRI signal in the cerebellum including the region of the dentate nucleus, the middle temporal gyrus and the orbitofrontal region. Decreases were also seen in several...