Andrew A. Maudsley

Mapping of brain metabolite distributions by volumetric proton MR spectroscopic imaging (MRSI).

Distributions of proton MR‐detected metabolites have been mapped throughout the brain in a group of normal subjects using a volumetric MR spectroscopic imaging (MRSI) acquisition with an interleaved water reference. Data were processed with intensity and spatial normalization to enable voxel‐based analysis methods to be applied across a group of subjects. Results demonstrate significant regional, tissue, and gender‐dependent variations of brain metabolite concentrations, and variations of these distributions with normal aging. The greatest alteration of metabolites with age was observed for white‐matter choline and creatine. An example of the utility of the normative metabolic reference information is then demonstrated for analysis of data acquired from a subject who suffered a traumatic brain injury. This study demonstrates the ability to obtain proton spectra from a wide region of the brain and to apply fully automated processing methods. The resultant data provide a normative reference for subsequent utilization for studies of brain injury and disease. Magn Reson Med, 2009.

3D phase encoding 1H spectroscopic imaging of human brain

A three-dimensional (3D) phase-encoding proton spectroscopic imaging method is presented for a whole body MRI/MRS system. Metabolite images at 2 T of choline, creatine, and N-acetyl aspartate (NAA) of normal brain were obtained with a spatial resolution of 1.5 cc. With PRESS volume preselection and outer volume suppression pulses, brain regions close to the skull could be studied without significant contamination by lipid and water signals.

Whole-Brain Proton MR Spectroscopic Imaging of Mild-to-Moderate Traumatic Brain Injury and Correlation with Neuropsychological Deficits

Changes in the distribution of the magnetic resonance (MR)-observable brain metabolites N-acetyl aspartate (NAA), total choline (Cho), and total creatine (Cre), following mild-to-moderate closed-head traumatic brain injury (mTBI) were evaluated using volumetric proton MR spectroscopic imaging (MRSI). Studies were carried out during the subacute time period following injury, and associations of metabolite indices with neuropsychological test (NPT) results were evaluated. Twenty-nine subjects with mTBI and Glasgow Coma Scale (GCS) scores of 10-15 were included. Differences in individual metabolite and metabolite ratio distributions relative to those of age-matched control subjects were evaluated, as well as analyses by hemispheric lobes and tissue types. Primary findings included a widespread decrease of NAA and NAA/Cre, and increases of Cho and Cho/NAA, within all lobes of the TBI subject group, and with the largest differences seen in white matter. Examination of the association between all of the metabolite measures and the NPT scores found the strongest negative correlations to occur in the frontal lobe and for Cho/NAA. No significant correlations were found between any of the MRSI or NPT measures and the GCS. These results demonstrate that significant and widespread alterations of brain metabolites occur as a result of mild-to-moderate TBI, and that these measures correlate with measures of cognitive performance.

Reproducibility of Serial Whole-Brain MR Spectroscopic Imaging

The reproducibility of serial measurements using a volumetric proton MR Spectroscopic Imaging (MRSI) acquisition implemented at 3 Tesla and with lipid suppression by inversion‐recovery has been evaluated. Data were acquired from two subjects at five time points, and processed using fully‐automated procedures that included rigid registration between studies. These data were analyzed to determine coefficients of variance (COV) for each metabolite and for metabolite ratio images based on an individual voxel analysis, as well as for average and grey‐matter and white‐matter values from atlas‐defined brain regions. The volumetric MRSI acquisition was found to obtain data of sufficient quality for analysis over 70 ± 6% of the total brain volume, and spatial distributions of the resultant COV values were found to reflect the known distributions of susceptibility‐induced magnetic field inhomogeneity. Median values of the resultant voxel‐based COVs were 6.2%, 7.2%, and 9.7% for N–acetylaspartate, creatine, and choline respectively. The corresponding mean values obtained following averaging over lobar‐scale brain regions within the cerebrum were 3.5%, 3.7%, and 5.2%. These results indicate that longitudinal volumetric MRSI studies with post‐acquisition registration can provide an intra‐subject reproducibility for voxel‐based analyses that is comparable to previously‐reported single‐voxel MRS measurements, while additionally enabling increased sensitivity by averaging over larger tissue volumes. Copyright

Detection and correction of frequency instabilities for volumetric 1H echo-planar spectroscopic imaging.

Spectral quality in 1H magnetic resonance spectroscopic imaging (MRSI) critically depends on the stability of the main magnetic field. For echo‐planar MRSI implemented at 3 T, temperature variation in the passive steel shims of the magnet system can lead to a significant drift in the resonance frequency. A method is presented that incorporates interleaved measurement of the instantaneous resonance frequency of a reference water signal into a volumetric MRSI sequence and allows correction for the drift during postprocessing. Results from normal human brain at 3 T indicate that the correction largely removes lineshape distortions, recovers metabolite signal loss, and improves spectral quality by reducing the width of spectral lines; however, particularly in inferior regions, other sources of distortion may be present that cause broadening of spectral lines. Magn Reson Med 53:465–469, 2005.

An intensity consistent filtering approach to the analysis of deformation tensor derived maps of brain shape.

Deformation tensor morphometry makes use of the derivatives of spatial transformations between anatomies, to provide highly localized volumetric maps of relative anatomical size. The analysis of such maps, however, has the challenge of describing the data in a way that allows the spatial scale and extent of the local shape properties to match those induced by the disease process being studied. This study examines an approach to the spatial filtering of transformation Jacobian maps created in multisubject studies of brain anatomy, which constrains the filter neighborhood within common structural boundaries present in the spatially normalized image data. The filtering incorporates information derived from the spatial normalization process, using a statistical framework to introduce a measure of uncertainty in local regional intensity correspondence following spatial normalisation. The proposed filtering approach is compared to the use of spatially invariant Gaussian filtering in the analysis of Jacobian determinant maps of brain shape and shape change in Alzheimers disease and normal aging. Results show significantly improved delineation of fine scale patterns of shape difference (in cross-sectional studies) and shape change (from multiple serial magnetic resonance imaging studies).

A Scalable Framework For Segmenting Magnetic Resonance Images

A fast, accurate and fully automatic method of segmenting magnetic resonance images of the human brain is introduced. The approach scales well allowing fast segmentations of fine resolution images. The approach is based on modifications of the soft clustering algorithm, fuzzy c-means, that enable it to scale to large data sets. Two types of modifications to create incremental versions of fuzzy c-means are discussed. They are much faster when compared to fuzzy c-means for medium to extremely large data sets because they work on successive subsets of the data. They are comparable in quality to application of fuzzy c-means to all of the data. The clustering algorithms coupled with inhomogeneity correction and smoothing are used to create a framework for automatically segmenting magnetic resonance images of the human brain. The framework is applied to a set of normal human brain volumes acquired from different magnetic resonance scanners using different head coils, acquisition parameters and field strengths. Results are compared to those from two widely used magnetic resonance image segmentation programs, Statistical Parametric Mapping and the FMRIB Software Library (FSL). The results are comparable to FSL while providing significant speed-up and better scalability to larger volumes of data.

Accurate template-based correction of brain MRI intensity distortion with application to dementia and aging

This paper examines an alternative approach to separating magnetic resonance imaging (MRI) intensity inhomogeneity from underlying tissue-intensity structure using a direct template-based paradigm. This permits the explicit spatial modeling of subtle intensity variations present in normal anatomy which may confound common retrospective correction techniques using criteria derived from a global intensity model. A fine-scale entropy driven spatial normalisation procedure is employed to map intensity distorted MR images to a tissue reference template. This allows a direct estimation of the relative bias field between template and subject MR images, from the ratio of their low-pass filtered intensity values. A tissue template for an aging individual is constructed and used to correct distortion in a set of data acquired as part of a study on dementia. A careful validation based on manual segmentation and correction of nine datasets with a range of anatomies and distortion levels is carried out. This reveals a consistent improvement in the removal of global intensity variation in terms of the agreement with a global manual bias estimate, and in the reduction in the coefficient of intensity variation in manually delineated regions of white matter.

Comparison of inversion recovery preparation schemes for lipid suppression in 1H MRSI of human brain

To reduce contamination from subcutaneous lipid regions in MR spectroscopic imaging (MRSI) of whole brain, lipid signals are often suppressed using T1 nulling methods. If a range of lipid T1 values is present, the suppression efficiency will be improved using multiple inversion recovery (MIR) preparation. This study compared single IR (SIR) and double IR (DIR) applied with a volumetric MRSI sequence at 1.5 T based on experimental measurement of lipid T1 and T2 relaxation rates. At short and medium echo times (TEs), an approximately 28–47% improvement in lipid suppression was achieved with DIR compared to SIR. However, it also led to a loss of 37–43% in signal‐to‐noise ratio (SNR) for metabolites. Thus, SIR appears to be the better choice for suppressing lipid signals and maintaining metabolite sensitivity. Magn Reson Med 49:903–908, 2003.

1H MRS of basal ganglia and thalamus in amyotrophic lateral sclerosis.

Previous studies have evaluated motor and extramotor cerebral cortical regions in patients with amyotrophic lateral sclerosis (ALS) using 1H MRS, but none have evaluated the thalamus or basal ganglia. The objective of this exploratory study was to evaluate the subclinical involvement of the basal ganglia and thalamus in patients with ALS using 1H MRS. Fourteen patients (52 ± 7 years) with sporadic definite ALS and 17 age‐matched controls were studied using volumetric MRSI on a 3‐T scanner. The concentration of the metabolites N‐acetylaspartate (NAA), choline (Cho) and their ratio (NAA/Cho) were obtained bilaterally from the basal ganglia (lentiform nucleus, caudate) and thalamus. The maximum rates of finger and foot tap and lip and tongue movements were obtained to assess extrapyramidal and pyramidal tract function. In patients with ALS, relative to controls, the NAA concentration was significantly lower (p < 0.02) in the basal ganglia and thalamus, and the Cho concentration was higher (p < 0.01) in these structures, except in the caudate (p = 0.04). Correspondingly, the NAA/Cho ratio was significantly lower (p < 0.01) in these structures, except in the caudate (p = 0.03), in patients than in controls. There were mild to strong correlations (r = 0.4–0.7) between the metabolites of the basal ganglia and finger tap, foot tap and lip and tongue movement rates. In conclusion, decreased NAA in the basal ganglia and thalamus and increased Cho and decreased NAA/Cho in the lentiform nucleus and thalamus are indicative of neuronal loss or dysfunction and alterations in choline‐containing membranes in these structures. Copyright