Purpose: To demonstrate an MRI method for directly visualizing amyloid-␤ (A␤) plaques in the APP/PS1 transgenic (tg) mouse brain in vivo, and show that T 1 relaxation rate increases progressively with Alzheimer's disease (AD)-related pathology in the tg mouse brain. Materials and Methods:We obtained in vivo MR images of a mouse model of AD (APP/PS1) that overexpresses human amyloid precursor protein, and measured T 1 via quantitative relaxometric maps.Results: A significant decrease in T 1 was observed in the cortex and hippocampus of 12-and 18-month-old animals compared to their age-matched controls. There was also a correlation between changes in T 1 and the age of the animals. ALZHEIMER'S DISEASE (AD) is the most common form of dementia in the elderly (1). Over 4 million people are affected by AD in the United States alone, and as the aging population increases, this number is expected to double by 2025 (2). The classic clinical symptoms of AD include memory loss and confusion. The neuropathological features are neurofibrillary tangles (NFTs) formed by paired helical filaments composed of tau protein, senile plaques (SPs) resulting from A␤ deposits, and neuron loss in the limbic and neocortical regions (3,4). Neuronal loss associated with early AD eventually leads to brain dysfunction and atrophy. Volumetric assessment methods are the current state of the art in magnetic resonance imaging (MRI) of AD in humans and in animal models of AD pathologies. These methods measure gross morphological changes and track disease progression, but do not provide information about biochemical changes. Conventional MRI of the brain, which relies on contrast generated by the variation of T 1 and T 2 or T 2 * relaxation times of water in tissue, has proven inadequate for observing authentic SPs and NFTs in vivo. This is primarily due to the high resolution and thin section (ϳ10 m) images required to visualize SPs, which currently are not achievable with MRI. However, interactions between macromolecules and bulk water, and changes in macromolecular content can be indirectly quantified by spatially mapping MR relaxation times. In these relaxometric maps, any change in relaxation times due to the presence of SPs will be reflected over an entire volume-averaged pixel, thereby providing an indirect method of detection without the need for very-high-resolution images. ConclusionIntriguing data suggesting that plaques can be detected in brain tissue specimens by T 2 *-weighted MRI have been reported (5); however, another study using similar methods failed to confirm this (6). Both studies were performed on formalin-fixed brain tissue specimens, and the MR characteristics of fixed tissue differ from those in vivo. T 2 -weighted MRI was employed to visualize plaques in a transgenic (tg) mouse model of AD ex vivo (7,8). Recent work has shown the possibility of detecting A␤ deposits in vivo in the APP/PS1 tg mouse model of AD using T 2 -and T 2 *-weighted MRI (9,10). The presence of iron in these plaques also exaggerates the actual size o...

A reduced specific absorption rate (SAR) version of the T 1 -weighted MR pulse sequence was designed and implemented. The reduced SAR method employs a partial k-space acquisition approach in which a full power spin-lock pulse is applied to only the central phase-encode lines of k-space, while the remainder of k-space receives a low-power spin-lock pulse. Acquisition of high-and low-power phase-encode lines are interspersed chronologically to minimize average power deposition. In this way, the majority of signal energy in the central portion of k-space receives full T 1 -weighting, while the average SAR of the overall acquisition can be reduced, thereby lowering the minimum safely allowable TR. The pulse sequence was used to create T 1 maps of a phantom, an in vivo mouse brain, and the brain of a human volunteer. In the images of the human brain, SAR was reduced by 40% while the measurements of T T 1 , the spin-lattice relaxation in the rotating frame of reference, provides an additional means of generating contrast in MR images that is unlike conventional proton density, T 1 -, or T 2 -weighting. T 1 -weighted MRI has been used for many applications, including imaging of muscle (1,2), breast (3), liver (4), brain (5,6), tumors (7,8), cartilage (9 -12), and perfusion studies (13,14). In general, T 1 -weighting can be added to a pulse sequence by including a pre-encoded pulse cluster consisting of a pair of nonselective 90°pulses separated by an on-resonance, long duration, low-power "spin-lock" (SL) pulse (Fig. 1). The amplitude of the SL pulse is commonly referred to in terms of its nutation frequency (␥B 1 ), generally on the order of hundreds of Hz. By setting the amplitude of the SL pulse to coincide with the prevailing frequencies of interaction between water and macromolecules, the T 1 parameter becomes dominated by effects of the macromolecular processes. The dependence of T 1 on the SL pulse amplitude introduces dispersion in the T 1 parameter, with T 1 approaching T 2 at low SL amplitudes and T 1 at high SL amplitudes (15). During the SL pulse, the magnetization decays exponentially according to T 1 , resulting in a T 1 -weighted signal. By collecting a series of T 1 -weighted images at varying durations of the SL pulse, T 1 can be measured using linear regression on a pixel-by-pixel basis to create a quantitative spatial map of T 1 values.The amount of RF energy per unit mass per unit time deposited into the sample during an imaging experiment is known as the specific absorption rate (SAR). The U.S. Food and Drug Administration (FDA) has established guidelines to regulate the allowable amount of SAR for an imaging experiment (16). In a T 1 -weighted sequence, the addition of the SL pulse cluster significantly increases SAR, thereby hindering the application of the technique for routine clinical use. With the increasing prevalence of high field (1.5 T or greater) scanners, SAR becomes more of a concern due to the quadratic dependence of SAR on Larmor frequency (␥B 0 ). The SAR constraint is most restrict...

In this work, the feasibility of using T 2 weighting as an MR contrast mechanism is evaluated. Axial images of a human brain were acquired using a single-slice spin-lock T 2 -weighted pulse sequence and compared to analogous T 2 -weighted images of the same slice. The contrast between white matter and gray matter in T 2 -weighted images was approximately 40% greater than that from T 2 -weighted data. These preliminary data suggest that the novel contrast mechanism of T 2 can be used to yield high-contrast T 2 -like images.

The high accuracy required in traditional ellipsometric measurements necessitates the absolute calibration of both the source and the detector. We demonstrate that these requirements can be circumvented by using a nonclassical source of light, namely, a twin-photon polarization-entangled source that produces type-II spontaneous parametric down-conversion, in conjunction with a novel polarization interferometer and coincidence-counting detection scheme. Our scheme exhibits two features that obviate the requirements of a calibrated source and detector. The first is the twin-photon nature of the source; we are guaranteed, on the detection of a photon in one of the arms of the setup, that its twin will be in the other, effectively serving as calibration of the source. The second is that the polarization entanglement of the source serves as an interferometer, thereby alleviating the need for calibrating the detector. The net result is that absolute ellipsometric data from a sample may be obtained. We present preliminary experimental results showing how the technique operates.