John G. Sled

A nonparametric method for automatic correction of intensity nonuniformity in MRI data

A novel approach to correcting for intensity nonuniformity in magnetic resonance (MR) data is described that achieves high performance without requiring a model of the tissue classes present. The method has the advantage that it can be applied at an early stage in an automated data analysis, before a tissue model is available. Described as nonparametric nonuniform intensity normalization (N3), the method is independent of pulse sequence and insensitive to pathological data that might otherwise violate model assumptions. To eliminate the dependence of the field estimate on anatomy, an iterative approach is employed to estimate both the multiplicative bias field and the distribution of the true tissue intensities. The performance of this method is evaluated using both real and simulated MR data.

Quantitative imaging of magnetization transfer exchange and relaxation properties in vivo using MRI

We describe a novel imaging technique that yields all of the observable properties of the binary spin‐bath model for magnetization transfer (MT) and demonstrate this method for in vivo studies of the human head. Based on a new model of the steady‐state behavior of the magnetization during a pulsed MT‐weighted imaging sequence, this approach yields parametric images of the fractional size of the restricted pool, the magnetization exchange rate, the T2 of the restricted pool, as well as the relaxation times in the free pool. Validated experimentally on agar gels and samples of uncooked beef, we demonstrate the methods application on two normal subjects and a patient with multiple sclerosis. Magn Reson Med 46:923–931, 2001.

Standing-wave and RF penetration artifacts caused by elliptic geometry: an electrodynamic analysis of MRI

Motivated by the observation that the diagonal pattern of intensity nonuniformity usually associated with linearly polarized radio-frequency (RF) coils is often present in neurological scans using circularly polarized coils, a theoretical analysis has been conducted of the intensity nonuniformity inherent in imaging an elliptically shaped object using 1.5-T magnets and circularly polarized RF coils. This first principle analysis clarifies, for the general case of conducting objects, the relationship between the excitation field and the reception sensitivity of circularly and linearly polarized coils. The results, validated experimentally using a standard spin-echo imaging sequence and an in vivo B/sub 1/ field mapping technique, are shown to be accurate to within 1%-2% root mean square, suggesting that these electromagnetic interactions with the object account for most of the intensity nonuniformity observed.

Qualitative and quantitative evaluation of six algorithms for correcting intensity nonuniformity effects.

The desire to correct intensity nonuniformity in magnetic resonance images has led to the proliferation of nonuniformity-correction (NUC) algorithms with different theoretical underpinnings. In order to provide end users with a rational basis for selecting a given algorithm for a specific neuroscientific application, we evaluated the performance of six NUC algorithms. We used simulated and real MRI data volumes, including six repeat scans of the same subject, in order to rank the accuracy, precision, and stability of the nonuniformity corrections. We also compared algorithms using data volumes from different subjects and different (1.5T and 3.0T) MRI scanners in order to relate differences in algorithmic performance to intersubject variability and/or differences in scanner performance. In phantom studies, the correlation of the extracted with the applied nonuniformity was highest in the transaxial (left-to-right) direction and lowest in the axial (top-to-bottom) direction. Two of the six algorithms demonstrated a high degree of stability, as measured by the iterative application of the algorithm to its corrected output. While none of the algorithms performed ideally under all circumstances, locally adaptive methods generally outperformed nonadaptive methods.

Three-dimensional cerebral vasculature of the CBA mouse brain: a magnetic resonance imaging and micro computed tomography study.

Studies of mouse cerebral vasculature to date have focused on the circle of Willis without examining the morphological distribution of blood vessels through the rest of the brain. Since mouse models are frequently used in brain-related studies, there is a need for a comprehensive cerebral vasculature atlas for the mouse with an emphasis on the location of vessels with respect to neuroanatomical structures, the watershed regions associated with specific arteries, as well as a consistent nomenclature of the cerebral vessels. This article describes such an atlas, based on a combination of magnetic resonance and computed tomography technology to yield high-resolution volumetric and vasculature data on CBA mouse. This three-dimensional vasculature dataset provides an anatomical resource for future mouse studies.

Longitudinal neuroanatomical changes determined by deformation-based morphometry in a mouse model of Alzheimer's disease.

Magnetic resonance imaging (MRI) of transgenic mice has the potential to provide valuable insight into the complex mechanisms underlying Alzheimers disease (AD). Quantification of pathological changes is typically performed using manual segmentation methods, and requires a priori hypotheses about anatomical structures for volumetric measurement. Alternatively, deformation-based morphometry (DBM) has been shown to be a powerful, automated technique for detecting anatomical differences between populations by examining the deformation fields used to nonlinearly warp MR images. In this multiple timepoint, in vivo study, we have applied an automated, unbiased technique for the creation of a nonlinear, population-specific reference space from which robust DBM analysis can be performed. A general, linear mixed-effects model framework was developed to follow the evolution of structural changes in mouse brain from 2.5 to 9 months of age, and to examine neuroanatomical differences between a transgenic (TG) APP/PS1 murine model of AD and wild-type (WT) littermates. Morphometric abnormalities in the TG group were localized to regions of the hippocampus, cortex, olfactory bulbs, stria terminalis, brain stem, cerebellum, and ventricles. Although volumetric reductions were detected in TG mice, no general brain atrophy was found, suggesting a developmental, rather than a degenerative, pathological process. Finally, we established a strong correlation between a DBM summary measure and manually segmented volumes for each image in the dataset. These results support the utility of DBM to study longitudinal morphological changes in mouse models of central nervous system diseases in an automated and exploratory fashion.

Automatic Quantification of Multiple Sclerosis Lesion Volume Using Stereotaxic Space

The quantitative analysis of MRI data is becoming increasingly important in the evaluation of therapies for the treatment of MS. This paper describes a processing environment for the automatic quantification of lesion load from large ensembles of MR volume data. The main components of this approach are stereotaxic transformation and multispectral classification, supported by pre- and postprocessing techniques to reduce noise and correct for intensity non-uniformities. The results of the automated approach are compared with those obtained by manual lesion delineation, showing a significant lesion volume correlation of 0.94.

Mutation I810N in the α3 isoform of Na+,K+-ATPase causes impairments in the sodium pump and hyperexcitability in the CNS

In a mouse mutagenesis screen, we isolated a mutant, Myshkin (Myk), with autosomal dominant complex partial and secondarily generalized seizures, a greatly reduced threshold for hippocampal seizures in vitro, posttetanic hyperexcitability of the CA3-CA1 hippocampal pathway, and neuronal degeneration in the hippocampus. Positional cloning and functional analysis revealed that Myk/+ mice carry a mutation (I810N) which renders the normally expressed Na+,K+-ATPase α3 isoform inactive. Total Na+,K+-ATPase activity was reduced by 42% in Myk/+ brain. The epilepsy in Myk/+ mice and in vitro hyperexcitability could be prevented by delivery of additional copies of wild-type Na+,K+-ATPase α3 by transgenesis, which also rescued Na+,K+-ATPase activity. Our findings reveal the functional significance of the Na+,K+-ATPase α3 isoform in the control of epileptiform activity and seizure behavior.

Cortical thickness measured from MRI in the YAC128 mouse model of Huntington's disease

A recent study found differences in localised regions of the cortex between the YAC128 mouse model of Huntingtons Disease (HD) and wild-type mice. There are, however, few tools to automatically examine shape differences in the cortices of mice. This paper describes an algorithm for automatically measuring cortical thickness across the entire cortex from MRI of fixed mouse brain specimens. An analysis of the variance of the method showed that, on average, a 50 microm (0.05 mm) localised difference in cortical thickness can be measured using MR scans. Applying these methods to 8-month-old YAC128 mouse model mice representing an early stage of HD, we found an increase in cortical thickness in the sensorimotor cortex, and also revealed regions wherein decreasing striatal volume correlated with increasing cortical thickness, indicating a potential compensatory response.

Magnetization transfer ratio in mild cognitive impairment and dementia of Alzheimer's type.

Almost half of the elderly subjects that are diagnosed with mild cognitive impairment (MCI) go on to develop dementia of Alzheimers type (DAT) over a 5-year follow-up. MCI and DAT subjects show regional decreases in the volume of brain structures, which correlate with the cognitive decline among these groups. Volumetric changes are found more consistently in the DAT group than in the MCI group. Since not all MCI subjects demonstrate volumetric decline, we propose that the underlying changes in the structural integrity of the brain, measured using magnetization transfer ratio (MTR), may be used as an additional predictor for abnormal cognitive decline in the elderly. Magnetic resonance (MR) images were obtained in 15 DAT, MCI, and elderly control subjects. Using automatic tissue classification, the brain region of each MR volume was segmented into gray matter and white matter. Mean and standard error of the mean MTR measured within the gray matter was found to be significantly lower in the MCI (30.77 +/-0.29; P = 0.037) and the DAT (29.37 +/-0.41; P = 0.000) group compared to the control group (32.11 +/-0.20). The MTR of white matter was significantly lower only in the DAT group. The gray matter volume was significantly lower (P = 0.000) in the DAT (387.29 +/-26.04 cm(3)) group compared to controls (532.93 +/-20.53 cm(3)) and MCI (464.64 +/-16.93 cm(3)). No significant differences were found in the white matter volume between the three groups. We conclude that changes in MTR are measurable even in the absence of detectable volumetric changes in gray and white matter in the MCI group. Furthermore, MTR changes may present a novel MRI measure for the early diagnosis of dementia of Alzheimers type.