Magnetic resonance imaging and computer image analysis in human clinical studies effectively identify abnormal neuroanatomy in disease populations. As more mouse models of neurological disorders are discovered, such an approach may prove useful for translational studies. Here, we demonstrate the effectiveness of a similar strategy for mouse neuroscience studies by phenotyping mice with the cerebellar deficient folia ( cdf ) mutation. Using in vivo multiple-mouse magnetic resonance imaging for increased throughput, we imaged groups of cdf mutant, heterozygous, and wild-type mice and made an atlas-based segmentation of the structures in 15 individual brains. We then performed computer automated volume measurements on the structures. We found a reduced cerebellar volume in the cdf mutants, which was expected, but we also found a new phenotype in the inferior colliculus and the olfactory bulbs. Subsequent local histology revealed additional cytoarchitectural abnormalities in the olfactory bulbs. This demonstra...

The early antecedents of cerebral palsy (CP) are unknown but are suspected to be due to hypoxia-ischemia (H-I). In our rabbit model of CP, the MRI biomarker, apparent diffusion coefficient (ADC) on diffusion-weighted imaging, predicted which fetuses will develop postnatal hypertonia. Surviving H-I fetuses experience reperfusion-reoxygenation but a subpopulation manifested a continued decline of ADC during early reperfusion-reoxygenation, which possibly represented greater brain injury (RepReOx). We hypothesized that oxidative stress in reperfusion-reoxygenation is a critical trigger for postnatal hypertonia. We investigated whether RepReOx predicted postnatal neurobehavior, indicated oxidative stress, and whether targeting antioxidants at RepReOx ameliorated motor deficits, which included testing of a new superoxide dismutase mimic (MnTnHex-2-PyP). Rabbit dams, 79% gestation (E25), were subjected to 40 min uterine ischemia. Fetal brain ADC was followed during H-I, immediate reperfusion-reoxygenation, and 4...

The brightness and color of a surface depends on its contrast with nearby surfaces. For example, a gray surface can appear very light when surrounded by a black surface or dark when surrounded by a white surface. Some theories suggest that perceived surface brightness and color is represented explicitly by neural signals in cortical visual field maps; these neural signals are not initiated by the stimulus itself but rather by the contrast signals at the borders. Here, we use functional magnetic resonance imaging (fMRI) to search for such neural “filling-in” signals. Although we find the usual strong relationship between local contrast and fMRI response, when perceived brightness or color changes are induced by modulating a surrounding field, rather than the surface itself, we find there is no corresponding local modulation in primary visual cortex or other nearby retinotopic maps. Moreover, when we model the obtained fMRI responses, we find strong evidence for contributions of both local and long-range edg...

Administration of adenosine receptor agonists increases cerebral blood flow (CBF,Van Wylen et al, 1989). We previously used arterial spin labeled magnetic resonance imaging (MRI) to map changes in CBF early after injection of the non-selective adenosine receptor agonist 2-chloroadenosine (2-CA) into rat brain (Kochanek et al, 2001). 2-4-fold increases in local and hemispheric CBF were seen. We now report the duration and receptor specificity of these effects. Anesthetized male Sprague-Dawley rats were injected with either saline vehicle (2 μl) or 2-CA (12 nmoles in 2 μl) into left dorsal hippocampus. At the NMR center, rats were anesthetized with pentobarbital and imaged at either ~3.5h or 1 day. MRI (perfusion, T1obs) was performed at 4.7T. CBF (ml/100g/min) in ipsilateral hippocampus was 217±50 (mean±SD) at ~3.5h after 2-CA injection vs 296±36 and 65±21 at ~24h in 2-CA and sham, respectively (p<0.05 for 2-CA vs sham at either time point). In cortex, CBF was 136±50 at ~3.5h after 2-CA injection vs 261±71 ...

We developed a fully automated method using iterative principal component analysis (PCA) to compute whole brain atrophy rates from sequential magnetic resonance images (MRI) of an individual subject. Baseline and follow-up MRI voxel intensities are treated as paired variables and brain locations with significant intensity differences between the two scans are identified using their distance from the PCA major axis. We compared the PCA method to the established but partly manual digital subtraction (DS) method in characterizing whole brain atrophy rates in patients with Alzheimer's dementia (AD) and normal controls. Baseline and follow-up MRI from 8 AD patients (54±8 years of age, Mini-Mental State Exame (MMSE) scores of 20±7.15) and 8 normal controls (54±8 years of age, MMSE scores of 29.5 ±0.8) were co-registered using SPM99 and analyzed, blind to group, using both the PCA and DS methods. The AD patients had significantly higher whole brain atrophy rates (percent change/year) than the normal controls usin...

High spatial and temporal resolution is critical to most research utilizing brain imaging techniques. Electroencephalography (EEG) offers high temporal resolution, but poor spatial information whereas functional magnetic resonance imaging (fMRI) yields little temporal information, but has a high spatial and true 3d-volume resolution. Therefore, many researchers utilize both techniques (sometimes even simultaneously) when conducting brain imaging experiments. The fact that fMRI scanners produce a loud pulsing noise during data acquisition is an obvious problem in studies that involve auditory stimuli. This sound cannot be completely shielded from the subjects and necessarily leads to different brain activation as compared to a silent environment hence contaminating the fMRI signal. The problem has been worked around by the development of the sparse sampling technique in which single volumes are acquired with long pauses between them before and after stimulus presentation. This technique is thought to minimi...

Stem cells are a promising source of neuro-regeneration for devastating brain injuries such as stroke. Stem cells labeled with a paramagnetic tracer have been visualized in the brain using magnetic resonance imaging (MRI). Stereotaxic implantation of cells allows precise localization but it is invasive and cannot deliver stem cells to the entire stroke area. In this study, we investigated the migration of intravenously delivered neural stem cells (NSCs) to the stroke area using MRI after transient middle cerebral artery occlusion (MCAO). Rat NSCs were isolated from the fetal striatum on embryonic day 16 and labeled with Feridex, a superparamagnetic iron oxide-containing nanoparticle that decreases T2*-weighted MRI signal intensity, using hemagglutinating virus of Japan envelopes to maximize labeling efficiency. Six rats received a MCAO for 60 min, and three of these rats received an intravenous injection of labeled NSCs 48 hours after MCAO while the other three rats acted as controls. MRI was performed on ...

Introduction: Most previous pharmacological MRI (phMRI) studies have used hypothesis-driven approaches for data analysis. However, the temporal pattern of brain response to a drug injection is not precisely known and head motion associated with drug administration can confound the results. Independent component analysis (ICA) is a data-driven method that does not require a priori knowledge about signal response patterns. In this study, we used group ICA to analyze phMRI BOLD data following cocaine and methylphenidate (MP) administration. Methods: Nine cocaine users received 3 IV drug injections (20mg/70kg cocaine, 10 and 20mg/70kg MP injected over 30sec). During each of 3 scan sessions, subjects received one IV injection of drug and 1 of saline. Whole brain BOLD images were acquired from 4 minutes before to 34 minutes after injection using a modified EPI sequence. A fast ICA algorithm was utilized to analyze the temporally concatenated functional data. An image voxel in an ICA component map was considered ...

Monitoring metabolic changes during ischemia with 1H-MRS may provide additional insights into the efficacy and the mechanism of potential neuroprotective agents. Pyruvate is an endogenous glucose metabolite, which shows substantial neuroprotective effects against several brain insults. However, the mechanism is still not fully understood. As an attempt to gain some insights, in the present study, we examined with MRS the effect of pyruvate in a rat model of permanent MCAO. Under general anesthesia, MCA was permanently occluded with fire-polished suture materials. Ischemic and non-ischemic contralateral brain regions (3 x 3 mm square with 2.5 mm thickness) were subjected to 1H-MRS. Pyruvate (125 mg/kg) was given intraperitoneally 30 min after the occlusion of MCA. In addition to MRS measurements, MR imagings, including diffusion-weighted imaging and T2-weighted imaging, were evaluated at 1, 2, and 6 hours following the ischemic onset. 24 h after MCAO, rats were sacrificed and their brains were stained with ...

The KIBRA gene has been associated with episodic memory in several recent reports; carriers of the T-allele show enhanced episodic memory performance relative to noncarriers. Gene expression studies in human and rodent species show high levels of KIBRA in the hippocampus, particularly in the subfields. The goal of the present study was to determine whether the KIBRA C→T polymorphism is also associated with volume differences in the human hippocampus and whether specific subfields are differentially affected by KIBRA genotype. High-resolution magnetic resonance imaging (T2-weighted, voxel size = 0.4 × 0.4 mm, in-plane) was used to manually segment hippocampal cornu ammonis (CA) subfields, dentate gyrus (DG), and the subiculum as well as adjacent medial temporal lobe cortices in healthy carriers and noncarriers of the KIBRA T-allele (rs17070145). Overall, we found that T-carriers had a larger hippocampal volume relative to noncarriers. The structural differences observed were specific to the CA fields and DG...