Mouse models provide useful tools to examine the genetic basis of disease. The Tennessee Mouse Genome Consortium screen for clinically relevant mouse models identified one mutant (178TNC) with reduced brain weight that was 3-5 standard deviations below the mean. We sought to validate this preliminary result and precisely quantify differences in brain size between mutant and wild-type animals using anatomical MRI scans with volumetric analysis. Freshly fixed age-matched mouse heads were secured within a custom-built T/R TEM RF coil using a locking mouth bar unit, ensuring reproducible head orientation and stabilization. Images were acquired using a proton density-weighted spin echo pulse sequence (TR=5000, TE=8.6, bandwidth=30K, voxel size=100x100x350 microns) on a Magnex 7 Tesla MRI scanner driven by a Varian console running VNMRJ. “Whole brain” regions for analysis were traced in coded data sets using XVOXTRACE. These regions included the olfactory bulbs and cerebellum and were demarcated at the level of ...

Background and Objective: Currently, there is no in vivo detection method for Alzheimer’s Abeta amyloidosis is available clinically. This study is to develop amyloid-specific in vivo imaging compounds for detecting and monitoring Alzheimer's disease Abeta amyloidogenesis. Methods: A novel amyloid-targeting Gadolinium (Gd) metal complex- Gd-XH1 has been designed, synthesized, and chemically characterized. MRI measurements (3T magnetic field strength) were made for solution mixes of Gd-XH1 complex and Abeta40/42 peptides, human serum albumin (HSA), or AD mouse and human brain tissue extracts filled in 4.5-mL hollow polypropylene plastic spheres (phantoms). The effects of Gd-XH1 on longitudinal (T1) magnetic relaxation rates were reported. Gd-DTPA was used as control MRI contrast imaging agent. We have also performed some preliminary studies on rodent models using Gd-XH1. Results: MRI phantom experiment shows that T1 decreases as the Abeta peptide concentration increases. There were little T1 signal changes w...

The phonological awareness, the ability to manipulate the abstract phonological representations of oral language, is crucial for learning process of reading. The developmental dyslexia shows the deficits during both auditory and visually presented phonological awareness tasks, and manipulating phonological representation may be the core deficits of developmental dyslexia. The neuroimaging studies have revealed the contribution of the similar neural substrates to both auditory and visual tasks. The less prevalence of dyslexia in Japanese suggests that Japanese language, which has simple letter-to-syllable relation summarized in Japanese syllabary table, has some advantages for the impaired children. To derive the neural substrates for the phonological manipulation of Japanese, we used functional MRI. The same vowel exchange tasks were performed in auditory (voices) and visual (kana letters) presentation in 19 normal volunteers. Different from previous studies in alphabetic languages, the neural substrates w...

The lateral geniculate nucleus (LGN) is the thalamic station in the retinocortical projection and has been studied extensively using single-cell recordings in nonhuman primates. It has proven difficult to activate the human LGN using fMRI due to its small size and deep location. We developed an fMRI paradigm that reliably activated the LGN to study its functions at the neural population level. Seven subjects were scanned in a 3 T head scanner using gradient echo EPI (TR=2s, TE = 30 ms, flip angle = 90 deg.). Checkerboard stimuli that were modulated in temporal frequency (0.5, 7.5, 20 Hz) or contrast (3 to 100%) were presented in alternation to the left or right hemifield in blocks of 16 seconds while subjects passively viewed a central fixation cross. Contrast response functions (CRFs) and temporal frequency functions (TRFs) were obtained in the LGN and in visual areas V1, V2, V3/VP, V3A, MT/MST and V4/TEO. CRFs increased approximately monotonically in the LGN and in visual cortex with a more rapid saturat...

Fractal geometry has been used to quantify the structure of a wide range of objects in biology and medicine. In this study we measured the fractal dimension of human cerebellum (CB) using MR CB images. Coronal MRI brain images covering the whole CB were collected from healthy adult subjects using a 1.5 T Siemens Vision scanner and 3-D Turboflash imaging sequence (TR/TE = 11.4/4.4ms, flip angle = 10°). Slice thickness was 2 mm, in-plane resolution was 1 x 1 mm2. The CB images were segmented out manually from the collected images, and then were resampled to be 1 mm in thickness. The resulted images were further resampled to a series of image sets with 3-D resolutions (Δ) of 1/4, 1/2, 2, 4 mm. The interfaces between white matter and gray matter in each image set were extracted using a user-modified contour algorithm in Matlab and a histogram-based thresholding. The rendered contour images were then binarized (i.e., voxels within the contours were assigned as 1, otherwise 0). A thinning method was applied to t...

phMRI is a new tool for studying drug effects on brain activity. The BOLD (blood oxygenation level dependent) contrast is based on changes in blood oxygenation following changes in brain metabolism but is also influenced by systemic cardiovascular and respiratory variables. We evaluated if systemic effects on BOLD can be separated from specific cerebral drug effects. In 3 ventilated rats under isoflurane anesthesia temperature, resp. gases, blood pressure (BP), heart rate, EEG and ECG were measured during MR scans (7T, SE-EPI). Each animal received i.v. saline after 10 min, 50mg/kg of the anxiogenic pentylenetetrazole (PTZ) after 20 min and 1 mg/kg diazepam after 30 min. For data analysis the BOLD time courses were detrended with the CO2 and BP curves. The positive PTZ response became smaller after detrending (obviously, a concomitant BP rise artificially enhanced the BOLD increase). The consecutive diazepam-induced BOLD decrease emerged stronger after detrending (systemic influences tended to mask the cer...

Brain fetal anatomy has been previously studied using echography , 2D MRI and post-mortem pathological examination. Fetus brain 3D MRI can offer a new perspective to study in vivo early stages of cerebral morphogenesis. Therefore, we performed MRI studies in five fetuses aged from 27 to 40 gestational weeks. The MRI was requested for medical reasons. MRI acquisition was performed on a 1.5 Tesla GE with the parameters: Fast Spin Echo T2, TR = 8000, TE = 120, voxel size: 1.4 x 1.4 x 4 mm. Acquisition time was about 2 minutes. No morphological pathology was detected. A semi-automatic cortical mantle detection was applied using a spherical deformable model whose deformations are driven by the contrast between CSF and gray matter. This procedure allows an anatomical 3D coherent reconstruction. An automatic curvature-based recognition of each sulcal roots was performed in each fetus brain and yielded a clear understanding of the dimples that mark the first stages of sulcal folding. The obtained 3D primal sketche...

A number of potential therapeutic approaches have been developed for the in vivo clearance of amyloid (Aβ) lesions, which characterize Alzheimer disease (AD). However, currently the definitive diagnosis of AD requires post-mortem examination. We present for the first time, a novel method for the detection of AD amyloid plaques by magnetic resonance micro-imaging(μMRI) using transgenic mouse models of AD. This method utilizes Aβ1-40 peptides which are labeled with either gadolinium (Gd) or monocrystalline iron oxide nanoparticles (MION). When either of these ligands are injected systemically with mannitol to transiently open the blood-brain barrier, we are able to image the majority of both early preamyloid Aβ deposits and Congo red positive amyloid plaques. A shows detection of amyloid lesions by μMRI, with B showing the corresponding immunohistochemically detected amyloid deposits. This type of approach could be used to make an early definitive diagnosis of AD, as well as allowing for the monitoring of am...

An enhanced response to d-amphetamine’s rewarding effects was found in MDD subjects in a previous study, suggesting the presence of a brain reward system dysfunction. In the present study, we performed f-MRI to localize the neuroanatomical substrates of the altered response to 30 mg d-amph p.o. in 6 depressed patients (mean HAMD=28; 3m, 3f; mean age=31) and 6 controls (3m, 3f; Mean age=32). F-MRI data were acquired at baseline and peak d-amph effect (1.5h to 2h). Subjects performed a battery of tasks at both time-points, followed by drug effect self-report measures (e.g. Addiction Research Centre Inventory). Pre-drug f-MRI data acquired during a simple task (i.e. pressing a button following series of visual cues) were contrasted with post-drug f-MRI data from the same task within each subject. ANOVA tests revealed that the depressed patients showed d-amph induced increased activation relative to controls in the anterior cingulate (rostral ACC/area 32)(t =3.18 uncorrected p < 0.01), a region involved in emo...

The effective connectivity of brain networks can be assessed using functional magnetic resonance imaging (fMRI) to quantify the effects of local electrical microstimulation (EM) on distributed neuronal activity. The delivery of EM to specific brain regions, particularly with layer specificity, requires MRI compatible equipment that provides fine control of a stimulating electrode’s position within the brain while minimizing imaging artifacts. To this end, we developed a microdrive made entirely of MRI compatible materials. The microdrive uses an integrated penetration grid to guide electrodes and relies on a microdrilling technique to eliminate the need for large craniotomies, further reducing implant maintenance and image distortions. The penetration grid additionally serves as a built-in MRI marker, providing a visible fiducial reference for estimating probe trajectories. Following the initial implant procedure, these features allow for multiple electrodes to be inserted, removed, and repositioned with m...