David Lavan Henderson

High-field magnetic resonance imaging of brain iron in Alzheimer disease.

Objectives: Increased iron deposition in the brain may occur in several neurodegenerative diseases, including Alzheimer disease (AD). Iron deposits shorten T2 relaxation times on T2-weighted magnetic resonance (MR) images. Iron-dependent contrast increases with magnetic field strength. We hypothesized that T2 mapping using 3 T MR imaging (MRI) can disclose differences between normal controls and AD subjects. Methods: High-resolution brain imaging protocols were developed and applied to 24 AD patients and 20 age-matched controls using 3 T MRI. Eight anatomical regions of interest were manually segmented, and T2 histograms were computed. A visual analysis technique, the heat map, was modified and applied to the large image data sets generated by these protocols. Results: A large number (163) of features from these histograms were examined, and 38 of these were significantly different (P < 0.05) between the groups. In the hippocampus, evidence was found for AD-related increases in iron deposition (shortened T2) and in the concentration of free tissue water (lengthened T2). Imaging of a section of postmortem brain before and after chemically extracting the iron established the presence of MRI-detectable iron in the hippocampus, cortex, and white matter in addition to brain regions traditionally viewed as containing high iron concentrations.

Microscopy image focus quality assessment by overlapping tile analysis

Digital microscopy is a field that is becoming increasingly popular for tissue imaging. Most digital microscopes have a limited field-of-view, requiring the acquisition of multiple tiles across the tissue that are then stitched together in software. During the acquisition, however, the microscope may intermittently fail to focus correctly, which will result in out-of-focus images that no longer provide diagnostic value. While many approaches have been proposed to address this using absolute measures of focus quality, we here introduce a novel approach that instead operates on the overlap regions between acquired images. This provides a relative measure that is independent of tissue type and staining protocol. These automatic measures can then be used to identify failed images that need to be re-acquired. Our quantitative and qualitative results on large datasets demonstrate the accuracy and robustness of the approach.

Evaluation of different multi-pinhole imaging geometries for SPECT imaging of Parkinsonian disorders

Focusing multi-pinhole (MP) collimators are increasingly being used for small animal as well as targeted VOI imaging. We use focused MP collimators to improve the resolution and sensitivity of photons detected from the striatal region of the brain. Simulations were based on activity distributions derived from clinical SPECT images of normal and Parkinson’s Disease patients injected with 99mTc-Trodat. Radioactive counts extracted from the clinical images were mapped onto regions of the Zubal brain phantom for input into the SPECT simulator. Simulated images were then generated modeling single pinhole (SP), nine pinhole (9PH) and 21 pinhole (21PH) collimators attached to one of the heads of a clinical SPECT scanner. The images were reconstructed using OSEM and evaluated after every iteration. The resulting image quality was evaluated using the ideal VOIs from the Zubal phantom for metrics such as contrast to noise ratio (CNR), bias, mean Uptake Ratio and standard error of the mean. In addition, for cross validation an automated feature detection and analysis tool was used for the detection and stratification of the simulated PD images. The CNR for the 9PH and 21PH was observed to increase by 66% and 81% while the corresponding noise levels dropped by 71% and 84%. Similarly the absolute bias was 64%, 28% and 22% for the SP, 9PH and 21PH respectively. Our results showed an improved performance of the MP collimators over the SP collimator configuration. The 21PH case performed well in terms of CNR and absolute bias, while the 9PH case resulted in the most accurate estimate of the true Uptake Ratio. The MP configurations were consistently observed to be superior to the single pinhole. In conclusion, focusing MP collimators were found to give improved quantification and better resolution compared to traditional SPECT acquisitions. The improved CNR enables more refined 3D visualization of the striatum, which could translate to better stratification of Parkinsonain disorders.

P2-104: Rapid T2-mapping of brain atrophy using a Talairach atlas correlates with neuropsychometric measures in classifying normal aging, mild cognitive impairment and stages of Alzheimer's disease

with lower levels of hippocampal neuronal metabolism as measured by MRS neurochemistry, but not hippocampal volume. Furthermore, decreased stride length is associated with smaller hippocampal volumes, but not hippocampal neurochemistry. If confirmed in larger samples, this pattern of results suggests that distinct neurobiological substrates may support decreased stride length and increased variability in older adults. Additional investigation is necessary to examine the longitudinal sequence of motor, cognitive, neurochemical and neuroanatomic changes in normal aging and dementia.

IC-P2-160: Rapid T2-mapping of brain atrophy using a Talairach atlas correlates with neuropsychometric measures in classifying normal aging, MCI and stages of Alzheimer's disease

Background: Quantitative MRI holds promise for early detection of AD. While it is well established that measures of hippocampal atrophy correlate with early diagnosis, its measurement is technically difficult and usually requires time consuming manual procedures. Semi-automated techniques are being developed which may speed this process and in combination with regional mapping of long T2 and thereby more water, one might develop a faster analysis of regional atrophy. Methods: T1 and T2, 3T MRI images were collected for 33 normal controls, 33 MCI (6 progressed over 3-5 years), 23 mild AD and 30 moderate AD. T1-weighted images were mapped to Talairach-Tournoux coordinates by manually defined landmarks using the AFNI image analysis package. Regional T2 measures were extracted from the co-registered T2 images using the atlas as a mask. Regions with increases in fluid vs. tissue were measured by analysis of the percentage of voxels where T2 was above 80ms. The subjects were tested by a neuropsychometric battery which included the Boston Naming Test, Visual Reproduction Fluency and the Hopkins Verbal Learning Test. Results: Significantly higher numbers to high T2 voxels were found in hippocampal and parahippocampal gyri in AD vs. normal aging. A subgroup of MCI (6) who progressed during the study showed a trend towards AD (Figure 1).