The cerebral deposition of amyloid ␤-peptide, a central event in Alzheimer's disease (AD) pathogenesis, begins several years before the onset of clinical symptoms. Noninvasive detection of AD pathology at this initial stage would facilitate intervention and enhance treatment success. In this study, high-field MRI was used to detect changes in regional brain MR relaxation times in three types of mice: 1) transgenic mice (PS/APP) carrying both mutant genes for amyloid precursor protein (APP) and presenilin (PS), which have high levels and clear accumulation of ␤-amyloid in several brain regions, starting from 10 weeks of age; 2) transgenic mice (PS) carrying only a mutant gene for presenilin (PS), which show subtly elevated levels of A␤-peptide without ␤-amyloid deposition; and 3) nontransgenic Cerebral deposits of the amyloid ␤-peptide and alterations of neurophysiology develop some years before Alzheimer's disease can be diagnosed clinically (1-3). By this stage, brain pathology is extensive and includes irreversible loss of neurons in brain regions essential for normal cognition (3). Because AD therapy is likely to be most successful when intervention occurs before neurons are irreversibly damaged or lost, noninvasive methods to detect early yet subtle changes in the brain would have considerable clinical value. Currently, there are no sensitive and specific biological markers for the preclinical stages of AD.Recent MRI studies of humans with mild cognitive impairment have shown that brain volume losses associated with neurodegeneration in the hippocampus have value in predicting increased risk for developing AD (4,5). Moreover, advances in high field strength MRI technology now raise the possibility that more subtle alterations of morphology or physiology preceding neurodegeneration might be detectable, including, in the case of AD, early effects of ␤-amyloid deposition. Since intrinsic MR parameters, such as transverse (T 2 ) and longitudinal (T 1 ) relaxation times are sensitive to changes in the biophysical environment of water, we hypothesized that the presence of increased deposition of ␤-amyloid in the brain would have an effect on these parameters.To investigate the possibility of early detection of the pathophysiology associated with AD, we studied PS/APP and PS transgenic mice together with nontransgenic (NTg) controls with MRI at 7 T. PS transgenic mice carry only a mutant gene for presenilin-1 (PS), which show subtly elevated levels of A␤-peptide without ␤-amyloid deposition in the brain (6). PS/APP transgenic mice express the human genes for amyloid precursor protein (APP) and presenilin-1 (PS) (7), which harbor mutations, APP K670N,M671L and PS M146V , known to cause familial AD (FAD) in humans. In these mice, ␤-amyloid begins to deposit at 10 -12 weeks of age and progressively accumulates as plaque-like lesions throughout their life span, reaching levels exceeding those in AD brain. Several other features of the human disease are also seen, including dystrophy of some neurites and mild local inf...

The goal of this work is to provide regional T 1 and T 2 values at a field strength of 7 T for the normal mouse brain at 6 weeks and 1 year old. A novel segmented snapshot FLASH sequence was used to measure T 1 in the hippocampus, corpus callosum, and the retrosplenial granular (RSG) cortex; T 2 measurements were made in the same regions using a single spin echo sequence repeated at six separate echo times. Historically, rats have been used routinely as disease models, but with the advent of transgenesis, and the economic advantages of creating transgenic mouse models of diseases, there is an increasing body of literature citing the use of mice in MRI. Much of the work is purely anatomical imaging. While values for T 1 and T 2 are published for normal and ischemic rat brain at 4.7 T (1,2), there is no equivalent study for the mouse brain, although there is a report of relaxation measurements in the hippocampus at 2 T (3) and a report of T 2 in the frontal cortex at 7 T (4). The ultimate aim of the work presented in this note is to characterize the T 1 and T 2 relaxation times in the mouse brain in order to fill a void in the literature for quantitative baseline values in an animal model of increasing importance.In addition, this study was designed to assess if a fast T 1 acquisition method could provide T 1 data comparable with the standard T 1 inversion recovery method. The mice used in the study are from the same background strain (B6/SW) that is (generally) used to generate transgenic mice with Alzheimer's pathology. Thus, this work is intended to provide baseline measurements of T 1 and T 2 in nontransgenic controls. Transgenic mice with Alzheimer's disease overexpress amyloid precursor protein. These animals are not easily maintained in the magnet under anesthesia for long periods, especially as they age. Fast image acquisitions, therefore, were an important criterion in this study but not at the expense of accuracy. Both T 1 and T 2 measurements were validated with phantom studies.Spin echo and inversion recovery methods are considered the workhorses of MRI for T 2 and T 1 measurement, respectively, despite their long acquisition times, especially in the latter case. Faster methods are necessary, particularly for T 1 measurement in vivo at 7 T, where the T 1 of brain tissue is on the order of several seconds. The TR necessary for standard inversion recovery measurements results in unacceptably long scan times. In order to achieve full relaxation, a TR time of approximately 5 T 1 is necessary, for even a low resolution (64 ϫ 64) standard inversion recovery with only a few time points along the recovery curve would require a total acquisition time of several hours.Echo planar Imaging can be used for high-speed and accurate T 1 mapping (5). However, the susceptibility distortion in a mouse brain at 7 T prohibits the use of this technique. A considerable increase in the speed of T 1 mapping can be achieved by implementing the LookLocker method (6). This method uses many low flip angle acquisitions to inspect a...

The apparent diffusion coefficient (ADC) and relaxation times of water were measured by magnetic resonance imaging (MRI) in the isolated turtle cerebellum during osmotic cell volume manipulation. The aim was to study effects of cell volume changes, a factor in ischemia and spreading depression, in isolation from considerations of blood flow and metabolism. Cerebella were superfused at 12–14°C with solutions ranging from 50–200% normal osmolarity. Hypotonic solutions, which are known to cause cell swelling, led to reductions of ADC and increases of T2, while hypertonic solutions had the opposite effect. This supports the concept that ADC varies with the extracellular space fraction and, combined with published data on extracellular ion diffusion, is consistent with fast or slow exchange models with effective diffusion coefficients that are approximately 1.7 times lower in intracellular than in extracellular space. Spin‐spin relaxation can be affected by osmotic disturbance, though such changes are not seen in all pathologies that cause cell swelling. Magn Reson Med 44:427–432, 2000. © 2000 Wiley‐Liss, Inc.