Studies on the Q175 Knock-in Model of Huntington's Disease Using Functional Imaging in Awake Mice: Evidence of Olfactory Dysfunction.

Blood oxygen level dependent (BOLD) imaging in awake mice was used to identify differences in brain activity between wild-type, HETzQ175, and HOMzQ175 genotypes in response to the odor of almond. The study was designed to see how alterations in the huntingtin gene in a mouse model of Huntington's disease would affect the perception and processing of almond odor, an evolutionarily conserved stimulus with high emotional and motivational valence. Moreover, the mice in this study were "odor naïve," i.e., never having smelled almond or any nuts. Using a segmented, annotated MRI atlas of the mouse and computational analysis, 17 out of 116 brain regions were identified as responding differently to almond odor across genotypes. These regions included the glomerulus of the olfactory bulb, forebrain cortex, anterior cingulate, subiculum, and dentate gyrus of the hippocampus, and several areas of the hypothalamus. In many cases, these regions showed a gene-dose effect with HETzQ175 mice showing a reduction in brain activity from wild-type that is further reduced in HOMzQ175 mice. Conspicuously absent were any differences in brain activity in the caudate/putamen, thalamus, CA3, and CA1 of the hippocampus and much of the cortex. The glomerulus of the olfactory bulb in HOMzQ175 mice showed a reduced change in BOLD signal intensity in response to almond odor as compared to the other phenotypes suggesting a deficit in olfactory sensitivity.

Functional magnetic resonance imaging in awake animals.

Awake animal imaging is becoming an important tool in behavioral neuroscience and preclinical drug discovery. Non-invasive ultra-high-field, functional magnetic resonance imaging (fMRI) provides a window to the mind, making it possible to image changes in brain activity across distributed, integrated neural circuits with high temporal and spatial resolution. In theory, changes in brain function, anatomy, and chemistry can be recorded in the same animal from early life into old age under stable or changing environmental conditions. This prospective capability of animal imaging to follow changes in brain neurobiology after genetic or environmental insult has great value to the fields of psychiatry and neurology and probably stands as the key advantage of MRI over other methods in the neuroscience toolbox. In addition, awake animal imaging offers the ability to record signal changes across the entire brain in seconds. When combined with the use of 3D segmented, annotated, brain atlases, and computational analysis, it is possible to reconstruct distributed, integrated neural circuits or 'fingerprints' of brain activity. These fingerprints can be used to characterize the activity and function of new psychotherapeutics in preclinical development and to study the neurobiology of integrated neural circuits controlling cognition and emotion. In this review, we describe the methods used to image awake animals and the recent advances in the radiofrequency electronics, pulse sequences, and the development of 3D segmented atlases and software for image analysis. Results from pharmacological MRI studies and from studies using provocation paradigms to elicit emotional responses are provided as a small sample of the number of different applications possible with awake animal imaging.

Bone mineral imaged in vivo by 31P solid state MRI of human wrists.

PURPOSE: To implement solid state (31)P MRI ((31)P SMRI) in a clinical scanner to visualize bone mineral. MATERIALS AND METHODS: Wrists of seven healthy volunteers were scanned. A quadrature wrist (31)P transmit/receive coil provided strong B(1) and good signal-to-noise ratio (SNR). A (1)H-(31)P frequency converter was constructed to enable detection of the (31)P signal by means of the (1)H channel. Data points lost in the receiver dead time were recovered by a second acquisition with longer dwell time and lower gradient strength. RESULTS: Three-dimensional (31)P images, showing only bone mineral of the wrist, were obtained with a clinical 3 Tesla (T) scanner. In the best overall case an image with isotropic resolution of ∼5.1 mm and SNR of 30 was obtained in 37 min. (31)P NMR properties (resonance line width 2 kHz and T(1) 17-19 s) of in vivo human bone mineral were measured. CONCLUSION: In vivo (31)P SMRI visualization of human wrist bone mineral with a clinical MR scanner is feasible with suitable modifications to circumvent the scanners' limitations in reception of short-T(2) signals. Frequency conversion methodology is useful for implementing (31)P SMRI measurements on scanners which do not have multinuclear capability or for which the multinuclear receiver dead time is excessive.

Helmholtz-pair transmit coil with integrated receive array for high-resolution MRI of trabecular bone in the distal tibia at 7T.

A Helmholtz-pair local transmit RF coil with an integrated four-element receive array RF coil and foot immobilization platform was designed and constructed for imaging the distal tibia in a whole-body 7T MRI scanner. Simulations and measurements of the B(1) field distribution of the transmit coil are described, along with SAR considerations for operation at 7T. Results of imaging the trabecular bone of three volunteers at 1.5T, 3T and 7T are presented, using identical 1.5T and 3T versions of the 7T four-element receive array. The spatially registered images reveal improved visibility for individual trabeculae and show average gains in SNR of 2.8× and 4.9× for imaging at 7T compared to 3T and 1.5T, respectively. The results thus display an approximately linear dependence of SNR with field strength and enable the practical utility of 7T scanners for micro-MRI of trabecular bone.