Introduction: Each whisker corresponds to a single functional column in the Barrel field. In vivo observation of activation induced by whisker stimulation is important for the analysis of the functional linkage. Activity-Induced Manganese-enhanced (AIM) MRI is reported as a hemodynamics independent method in functional MRI study (Lin, et al.). Mn2+ enters neurons through voltage-gated Ca2+ channels during nerve action potential and leads to signal enhancement in active brain areas. The purpose of this study is to detect brain activation during whisker stimulation with high spatial resolution using hemodynamics independent AIM MRI. Materials and Methods: Male SD rats were divided into 3 groups: normal control (n = 5), multi whiskers stimulation (n = 5), and single whisker stimulation (n = 5). Animals were prepared using previously described methods (Aoki I, NMR in Biomed. 2004, 17:1-12). The blood brain barrier was disrupted by 25% D-mannitol. Whisker E1 was stimulated with 2Hz frequency during the MnCl2 in...

Objective: Evidence suggests that inflammatory processes may cause neurodegeneration in Alzheimer's disease (AD). This project assessed a new diffusion-weighted magnetic resonance imaging method, DIFRAD-FSE, in identifying early markers of AD in individuals at risk. DIFRAD can be used to evaluate inflammation and is useful for assessing white matter (WM) integrity. Methods: Subjects were 32 adults (66-87 yrs): 16 with risk for AD and 16 without. Risk was defined as presence of the APOE e4 allele, and/or by presence of a 1st order relative with probable AD. A neuropsychological test battery yielded 2 composite scores for memory and executive function. Using a 3T scanner, 14 coronal sections were acquired from the medial temporal lobe (MTL). Fractional Anisotropy (FA) and Average Diffusion Coefficients (ADC) were determined for: splenium of the corpus callosum, WM of the temporal stem (TStem), and hippocampus (HC). We predicted a drop in brain integrity (increased ADC and decreased FA) in subjects with risk....

The development of manganese as a transneuronally-transported, MRI-visible tract tracer has made in vivo identification of multi-stage anatomical pathways feasible. Using this technique, we can localize sites to which groups of neurons project, and target neuronal recordings from directly connected regions. Because manganese is a known neurotoxin, however, we need to determine to what extent intracerebral injections of this tracer result in neuronal damage. We injected manganese chloride (MnCl2, 0.5uL, 800mM) into the orbitofrontal cortex (OFC) of a rhesus monkey. We obtained high-resolution 3D MR images of the brain at 4.7T, with contrast optimized for Mn. We recorded single neurons in OFC while the monkey performed a color detection task before and after Mn injections. Finally, we processed the brain tissue histochemically for Nissl substance, tyrosine hydroxylase, and parvalbumin. Manganese injection sites were centered in area 13 of OFC. On post-injection day 4, we observed enhancements due to Mn trans...

The subthalamic nucleus (STh) is a small subcortical structure which is involved in regulating motor as well as cognitive functions. Due to its small size and close proximity to other small subcortical structures, it has been a challenge to localize and visualize it using magnetic resonance imaging (MRI). Currently there are several standard atlases available that are used to localize the STh in functional MRI studies and clinical procedures such as deep brain stimulation (DBS). DBS is an increasingly common neurosurgical procedure that has been successfully used to alleviate motor symptoms present in Parkinson's disease. However, current atlases are based on low sample sizes and restricted age ranges ([Schaltenbrand and Wahren, 1977][1]), and hence the use of these atlases effectively ignores the substantial structural brain changes that are associated with aging. In the present study, ultra-high field 7 tesla (T) magnetic resonance imaging (MRI) in humans was used to visualize and segment the STh in youn...

Functional MRI in conscious animals provides a new opportunity in drug discovery to identify patterns of brain activity characteristic of different classes of psychotropic molecules. To this end, rats were tested with functionally different classes of drugs used to treat schizophrenia - atypical (clozapine, respiridone) and typical (chlorpromazine, haloperidol) antipsychotics. Rats showed a dose-dependent (change in brain activity dominated by negative BOLD signal) within 10-15 min of iv injection of drug. Since the efficacy of these drugs is related, in part, to their affinity for dopamine receptors, animals were challenged with an ICV injection of apomorphine following neuroleptic treatment. While several areas of the brain were activated by apomorphine administration alone, the most robust increase in BOLD signal intensity occurred in the prefrontal cortex. The typical antipsychotics, haloperidol and chlorpromazine blocked the action of apomorphine in the prefrontal cortex, while respiradol and clozapin...

Objectives: The purpose of the present study is to investigate the cortical changes in pain perception when applying different kind of conditioning sensory stimuli, namely acupuncture (Meridian) and acupuncture-like (Sham) stimuli and to show that these stimuli are essentially those of the stress-inducing stimuli and the results are the consequence of the HPA axis reflexes. Methods: Brain activation was observed with functional magnetic resonance imaging (fMRI) using a set of thermal stimuli as pain stimulus which induced by immersing the index finger into a hot water bath, approximately 51~52°C for 30 seconds. The experiment is performed by applying the pain following Meridian acupuncture and Sham acupuncture which applying needling to the traditionally known acupuncture points and points nearby but not those. These stimuli were manually twirling or rotating of a needle with approximately 1 Hz for a period of 30 seconds and rest period of 30 seconds with repetition of 5 times. Results: The results were co...

Pups reinforcing properties are so robust that they compete with self-administration of cocaine (Hecht et al., Dev Psychobiol 35:136,1999). Indeed, postpartum dams bar press for pups in an operant response paradigm (Lee et al., Behav Brain Res 108:215, 2000). The present studies use fMRI and 3D computational analyses to compare pup-induced vs cocaine-induced changes in brain activity in lactating dams. Mothers were imaged for postnatal days 4 – 8 in response to pups (n=6) or ICV cocaine (20ug/10 ul) (n=6). A third group (n=6), imaged virgin females in response to ICV cocaine. A multi-slice fast spin echo sequence acquired twelve 1.2mm slices in 6s. All imaging consisted of 3 min (30 rep.) of control followed by 5 min (50 rep.) of stimulus. A 4.7T/40cm horiz. magnet was used. The results for n subjects in each group were presented individually and as group composites. The analysis involved three major steps registration, segmentation and statistical analysis. Subjects were registered to a fully segmented 3D...

Stereotactic placement of deep brain stimulation (DBS) leads for the treatment of movement disorders has traditionally been guided by microrecording and macrostimulation in awake patients, with subsequent confirmation by MRI after the lead’s stylet has been removed. When placement errors occur, the surgery must be repeated and the lead replaced. Visual guidance by concurrent MRI would improve placement accuracy and reduce the need for repeated surgeries. An MRI-compatible trajectory guidance system (IGN) has been developed to fix DBS leads in place without removing the stylet, and allow remote adjustment of the lead position as needed. In preparation for clinical applications, we performed safety tests of this device in a 1.5-Tesla Siemens Sonata MR system. We evaluated local temperature changes using clinically relevant and ¨worst-case¨ MRI sequences in a semi-solid, gel-filled phantom. The lead tip (Medtronic), with stylet in place, was immersed into the phantom using the trajectory guide and remote intr...

Previously, we have demonstrated that fMRI can be used to map age-associated changes in nigrostriatal system with dopaminergic stimulation in normal rhesus monkeys (NeuroImage 14: 1159-1167, 2001). In the present study, fMRI was used to map dopamine (DA) receptor-mediated blood oxygen level dependent (BOLD) changes indicative of neuronal activity in the basal ganglia of hemiparkinsonian rhesus monkeys. Unilateral infusion of MPTP via the right carotid artery was used to induce unilateral parkinsonian features in 12 monkeys; 3 age-matched normal monkeys served as controls. Apomorphine (APO, 0.1mg/kg s.c.), a mixed dopamine D1/D2 receptor agonist, evoked strong activation in the MPTP-lesioned caudate nucleus, putamen, globus pallidus (GP) and substantia nigra (SN) with little change detected on the intact side of these structures. The activation on the lesioned side persisted in the GP until administration 15 min later of the D1 receptor antagonist (SCH-23390, 0.1mg/kg i.m.). APO-induced activation was rever...

Deep brain stimulation (DBS) is used increasingly in the field of movement disorders. The implanted electrodes create not only a priori risk to patient safety during MR imaging, but also a unique opportunity in the collection of functional MRI (fMRI) data conditioned by direct neural stimulation. We performed safety tests of commercially available bilateral neurostimulation systems (Soletra® 7482, Medtronic), extensions, and leads in a clinical 1.5 T MR system (Siemens, Germany) across a range of MR acquisitions of typical and worst case scenarios. The primary safety risk arises from RF induction of current through the electrode leads. It depends on the RF energy deposited during specific imaging sequences, on physical properties of the electrodes, and on the low impedance and/or resonant paths within the lead geometry. In vitro testing was performed using a phantom filled with a semisolid gel simulating the thermal convection and dielectric properties of human tissues. Each DBS electrode was positioned wi...