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Biomedical subjects

M I Miller

Publications and source records attributed to M I Miller.

At least 19 recordsLinked to original sources
PubMed2005

Preclinical detection of Alzheimer's disease: hippocampal shape and volume predict dementia onset in the elderly.

Structural deformity of the hippocampus is characteristic of individuals with very mild and mild forms of dementia of the Alzheimer type (DAT). The purpose of this study was to determine whether a similar deformity of the hippocampus can predict the onset of dementia in nondemented elders. Using high dimensional diffeomorphic transformations of a neuroanatomical template, hippocampal volumes and surfaces were defined in 49 nondemented elders; the hippocampal surface was subsequently partitioned into three zones (i.e., lateral, superior and inferior-medial), which were proximal to the underlying CA1 subfield, CA2-4 subfields plus dentate gyrus, and subiculum, respectively. Annual clinical assessments using the Clinical Dementia Rating scale (CDR), where CDR 0 indicates no dementia and CDR 0.5 indicates very mild dementia, were then performed for a mean of 4.9 years (range 0.9-7.1 years) to monitor subjects who converted from CDR 0 to CDR 0.5. Inward variation of the lateral zone and left hippocampal volume significantly predicted conversion to CDR 0.5 in separate Cox proportional hazards models. When hippocampal surface variation and volume were included in a single model, inward variation of the lateral zone of the left hippocampal surface was selected as the only significant predictor of conversion. The pattern of hippocampal surface deformation observed in nondemented subjects who later converted to CDR 0.5 was similar to the pattern of hippocampal surface deformation previously observed to discriminate subjects with very mild DAT and nondemented subjects. These results suggest that inward deformation of the left hippocampal surface in a zone corresponding to the CA1 subfield is an early predictor of the onset of DAT in nondemented elderly subjects.

Aged↗
PubMed2004

Statistics on diffeomorphisms via tangent space representations.

In this paper, we present a linear setting for statistical analysis of shape and an optimization approach based on a recent derivation of a conservation of momentum law for the geodesics of diffeomorphic flow. Once a template is fixed, the space of initial momentum becomes an appropriate space for studying shape via geodesic flow since the flow at any point along the geodesic is completely determined by the momentum at the origin through geodesic shooting equations. The space of initial momentum provides a linear representation of the nonlinear diffeomorphic shape space in which linear statistical analysis can be applied. Specializing to the landmark matching problem of Computational Anatomy, we derive an algorithm for solving the variational problem with respect to the initial momentum and demonstrate principal component analysis (PCA) in this setting with three-dimensional face and hippocampus databases.

Algorithms↗
PubMed2003

Labeled cortical mantle distance maps of the cingulate quantify differences between dementia of the Alzheimer type and healthy aging.

The cingulate gyri in 37 subjects with and without early dementia of the Alzheimer type (DAT) were studied by using MRI at 1.0 mm3 isotropic resolution. Groups were segregated into young controls (n = 10), age-matched normal controls (n = 10), very mild DAT (n = 8), and mild DAT (n = 9). By using automated Bayesian segmentation of the cortex and gray matter/white matter (GM/WM) isosurface generation, tissue compartments were labeled into gray, white, and cerebrospinal fluid as a function of distance from the GM/WM isosurface. Cortical mantle distance maps are generated profiling the GM volume and cortical mantle distribution as a function of distance from the cortical surface. Probabilistic tests based on generalizations of Wilcoxon-Mann-Whitney tests were applied to quantify cortical mantle distribution changes with normal and abnormal aging. We find no significant change between young controls and healthy aging as measured by the GM volume and cortical mantle distribution as a function of distance in both anterior and posterior regions of the cingulate. Significant progression of GM loss is seen in the very mild DAT and mild DAT groups in all areas of the cingulate. Posterior regions show both GM volume loss as well as significant cortical mantle distribution decrease with the onset of mild DAT. The "shape of the cortical mantle" as measured by the cortical mantle distance profiles manifests a pronounced increase in variability with mild DAT.

Adult↗
PubMed2003

Dynamic programming generation of boundaries of local coordinatized submanifolds in the neocortex: application to the planum temporale.

Dynamic programming is used to define boundaries of cortical submanifolds with focus on the planum temporale (PT) of the superior temporal gyrus (STG), which has been implicated in a variety of neuropsychiatric disorders. To this end, automated methods are used to generate the PT manifold from 10 high-resolution MRI subvolumes ROI masks encompassing the STG. A procedure to define the subvolume ROI masks from original MRI brain scans is developed. Bayesian segmentation is then used to segment the subvolumes into cerebrospinal fluid, gray matter (GM), and white matter (WM). 3D isocontouring using the intensity value at which there is equal probability of GM and WM is used to reconstruct the triangulated graph representing the STG cortical surface, enabling principal curvature at each point on the graph to be computed. Dynamic programming is used to delineate the PT manifold by tracking principal curves from the retro-insular end of the Heschl's gyrus (HG) to the STG, along the posterior STG up to the start of the ramus and back to the retro-insular end of the HG. A coordinate system is then defined on the PT manifold. The origin is defined by the retro-insular end of the HG and the y-axis passes through the point on the posterior STG where the ramus begins. Automated labeling of GM in the STG is robust with L(1) distances between Bayesian and manual segmentation in the range 0.001-0.12 (n = 20). PT reconstruction is also robust with 90% of the vertices of the reconstructed PT within about 1 voxel (n = 20) from semiautomated contours. Finally, the reliability index (based on interrater intraclass correlation) for the surface area derived from repeated reconstructions is 0.96 for the left PT and 0.94 for the right PT, thus demonstrating the robustness of dynamic programming in defining a coordinate system on the PT. It provides a method with potential significance in the study of neuropsychiatric disorders.

Algorithms↗
PubMed2001

Statistical analysis of hippocampal asymmetry in schizophrenia.

The asymmetry of brain structures has been studied in schizophrenia to better understand its underlying neurobiology. Brain regions of interest have previously been characterized by volumes, cross-sectional and surface areas, and lengths. Using high-dimensional brain mapping, we have developed a statistical method for analyzing patterns of left-right asymmetry of the human hippocampus taken from high-resolution MR scans. We introduce asymmetry measures that capture differences in the patterns of high-dimensional vector fields between the left and right hippocampus surfaces. In 15 pairs of subjects previously studied (J. G. Csernansky et al., 1998, Proc. Natl. Acad. Sci. USA 95, 11406-11411). we define the difference in hippocampal asymmetry patterns between the groups. Volume analysis indicated a large normative asymmetry between left and right hippocampus (R > L), and shape analysis allowed us to visualize the normative asymmetry pattern of the hippocampal surfaces. We observed that the right hippocampus was wider along its lateral side in both schizophrenia and control subjects. Also, while patterns of hippocampal asymmetry were generally similar in the schizophrenia and control groups, a principal component analysis based on left-right asymmetry vector fields detected a statistically significant difference between the two groups, specifically related to the subiculum.

Brain Mapping↗
PubMed2001

Validating cortical surface analysis of medial prefrontal cortex.

This paper describes cortical analysis of 19 high resolution MRI subvolumes of medial prefrontal cortex (MPFC), a region that has been implicated in major depressive disorder. An automated Bayesian segmentation is used to delineate the MRI subvolumes into cerebrospinal fluid (CSF), gray matter (GM), white matter (WM), and partial volumes of either CSF/GM or GM/WM. The intensity value at which there is equal probability of GM and GM/WM partial volume is used to reconstruct MPFC cortical surfaces based on a 3-D isocontouring algorithm. The segmented data and the generated surfaces are validated by comparison with hand segmented data and semiautomated contours, respectively. The L(1) distances between Bayesian and hand segmented data are 0.05-0.10 (n = 5). Fifty percent of the voxels of the reconstructed surface lie within 0.12-0.28 mm (n = 14) from the semiautomated contours. Cortical thickness metrics are generated in the form of frequency of occurrence histograms for GM and WM labelled voxels as a function of their position from the cortical surface. An algorithm to compute the surface area of the GM/WM interface of the MPFC subvolume is described. These methods represent a novel approach to morphometric chacterization of regional cortex features which may be important in the study of psychiatric disorders such as major depression.

Adult↗
PubMed2001

Mapping visual cortex in monkeys and humans using surface-based atlases.

We have used surface-based atlases of the cerebral cortex to analyze the functional organization of visual cortex in humans and macaque monkeys. The macaque atlas contains multiple partitioning schemes for visual cortex, including a probabilistic atlas of visual areas derived from a recent architectonic study, plus summary schemes that reflect a combination of physiological and anatomical evidence. The human atlas includes a probabilistic map of eight topographically organized visual areas recently mapped using functional MRI. To facilitate comparisons between species, we used surface-based warping to bring functional and geographic landmarks on the macaque map into register with corresponding landmarks on the human map. The results suggest that extrastriate visual cortex outside the known topographically organized areas is dramatically expanded in human compared to macaque cortex, particularly in the parietal lobe.

Animals↗
PubMed2000

Early DAT is distinguished from aging by high-dimensional mapping of the hippocampus. Dementia of the Alzheimer type.

OBJECTIVE: To determine the feasibility of using high-dimensional brain mapping (HDBM) to assess the structure of the hippocampus in older human subjects, and to compare measurements of hippocampal volume and shape in subjects with early dementia of the Alzheimer type (DAT) and in healthy elderly and younger control subjects. BACKGROUND: HDBM represents the typical structures of the brain via the construction of templates and addresses their variability by probabilistic transformations applied to the templates. Local application of the transformations throughout the brain (i.e., high dimensionality) makes HDBM especially valuable for defining subtle deformities in brain structures such as the hippocampus. METHODS: MR scans were obtained in 18 subjects with very mild DAT, 18 healthy elderly subjects, and 15 healthy younger subjects. HDBM was used to obtain estimates of left and right hippocampal volume and eigenvectors that represented the principal dimensions of hippocampal shape differences among the subject groups. RESULTS: Hippocampal volume loss and shape deformities observed in subjects with DAT distinguished them from both elderly and younger control subjects. The pattern of hippocampal deformities in subjects with DAT was largely symmetric and suggested damage to the CA1 hippocampal subfield. Hippocampal shape changes were also observed in healthy elderly subjects, which distinguished them from healthy younger subjects. These shape changes occurred in a pattern distinct from the pattern seen in DAT and were not associated with substantial volume loss. CONCLUSIONS: Assessments of hippocampal volume and shape derived from HDBM may be useful in distinguishing early DAT from healthy aging.

Aged↗
PubMed2000

Bayesian construction of geometrically based cortical thickness metrics.

This paper describes the construction of cortical metrics quantifying the probabilistic occurrence of gray matter, white matter, and cerebrospinal fluid compartments in their correlation to the geometry of the neocortex as measured in 0.5-1.0 mm magnetic resonance imagery. These cortical profiles represent the density of the tissue types as a function of distance to the cortical surface. These metrics are consistent when generated across multiple brains indicating a fundamental property of the neocortex. Methods are proposed for incorporating such metrics into automated Bayes segmentation.

Anthropometry↗
PubMed2000

Mesial temporal sclerosis and temporal lobe epilepsy: MR imaging deformation-based segmentation of the hippocampus in five patients.

In five patients with mesial temporal sclerosis, the authors verified the precision and reproducibility of hippocampal segmentations with deformation-based magnetic resonance (MR) imaging. The overall percentage overlap between automated segmentations was 92.8% (SD, 3.5%), between manual segmentations was 73.1% (SD, 9.5%), and between automated and manual segmentations was 74.8% (SD, 10.3%). Deformation-based hippocampal segmentations provided a precise method of hippocampal volume measurement in this patient population.

Adult↗
PubMed1999

Brain segmentation and the generation of cortical surfaces.

This paper describes methods for white matter segmentation in brain images and the generation of cortical surfaces from the segmentations. We have developed a system that allows a user to start with a brain volume, obtained by modalities such as MRI or cryosection, and constructs a complete digital representation of the cortical surface. The methodology consists of three basic components: local parametric modeling and Bayesian segmentation; surface generation and local quadratic coordinate fitting; and surface editing. Segmentations are computed by parametrically fitting known density functions to the histogram of the image using the expectation maximization algorithm [DLR77]. The parametric fits are obtained locally rather than globally over the whole volume to overcome local variations in gray levels. To represent the boundary of the gray and white matter we use triangulated meshes generated using isosurface generation algorithms [GH95]. A complete system of local parametric quadratic charts [JWM+95] is superimposed on the triangulated graph to facilitate smoothing and geodesic curve tracking. Algorithms for surface editing include extraction of the largest closed surface. Results for several macaque brains are presented comparing automated and hand surface generation.

Algorithms↗
PubMed1998

Hippocampal morphometry in schizophrenia by high dimensional brain mapping.

Theories of the pathophysiology of schizophrenia have implicated the hippocampus, but controversy remains regarding hippocampal abnormalities in patients with schizophrenia. In vivo studies of hippocampal anatomy using high resolution magnetic resonance scanning and manual methods for volumetric measurement have yielded inconclusive results, perhaps because of the normal variability in hippocampal volume and the error involved in manual measurement techniques. To resolve this controversy, high dimensional transformations of a computerized brain template were used to compare hippocampal volumes and shape characteristics in 15 matched pairs of schizophrenia and control subjects. The transformations were derived from principles of general pattern matching and were constrained according to the physical properties of fluids. The analysis and comparison of hippocampal shapes based on these transformations were far superior to the comparison of hippocampal volumes or other global indices of hippocampal anatomy in showing a statistically significant difference between the two groups. In the schizophrenia subjects, hippocampal shape deformations were found to be localized to subregions of the structure that send projections to prefrontal cortex. The results of this study demonstrate that abnormalities of hippocampal anatomy occur in schizophrenia and support current hypotheses that schizophrenia involves a disturbance of hippocampal-prefrontal connections. These results also show that comparisons of neuroanatomical shapes can be more informative than volume comparisons for identifying individuals with neuropsychiatric diseases, such as schizophrenia.

Brain Mapping↗
PubMed1998

Functional and structural mapping of human cerebral cortex: solutions are in the surfaces.

The human cerebral cortex is notorious for the depth and irregularity of its convolutions and for its variability from one individual to the next. These complexities of cortical geography have been a chronic impediment to studies of functional specialization in the cortex. In this report, we discuss ways to compensate for the convolutions by using a combination of strategies whose common denominator involves explicit reconstructions of the cortical surface. Surface-based visualization involves reconstructing cortical surfaces and displaying them, along with associated experimental data, in various complementary formats (including three-dimensional native configurations, two-dimensional slices, extensively smoothed surfaces, ellipsoidal representations, and cortical flat maps). Generating these representations for the cortex of the Visible Man leads to a surface-based atlas that has important advantages over conventional stereotaxic atlases as a substrate for displaying and analyzing large amounts of experimental data. We illustrate this by showing the relationship between functionally specialized regions and topographically organized areas in human visual cortex. Surface-based warping allows data to be mapped from individual hemispheres to a surface-based atlas while respecting surface topology, improving registration of identifiable landmarks, and minimizing unwanted distortions. Surface-based warping also can aid in comparisons between species, which we illustrate by warping a macaque flat map to match the shape of a human flat map. Collectively, these approaches will allow more refined analyses of commonalities as well as individual differences in the functional organization of primate cerebral cortex.

Anatomy, Cross-Sectional↗
PubMed1998

Effects of finasteride on hematuria associated with benign prostatic hyperplasia: long-term follow-up.

OBJECTIVES: To report long-term follow-up in 18 patients with gross hematuria associated with benign prostatic hyperplasia (BPH) who have been treated with finasteride and to report preliminary follow-up in an additional 10 patients. METHODS: The charts of the 18 original patients, and 10 additional patients who had been placed on finasteride (5 mg daily) for intermittent gross hematuria associated with BPH, were reviewed. All had evaluations that were negative for tumor. A hematuria grading system was devised using grades 0, 1, 2, and 3 (grade 0 the least severe, grade 3 the most severe hematuria). RESULTS: Sixteen of 18 patients have continued finasteride therapy. Mean follow-up is 31 months (range 10 to 47). Twelve had undergone prior prostatectomy. In this group, 3 patients had grade 1, 5 grade 2, and 4 grade 3 hematuria prior to treatment with finasteride. During finasteride therapy, 9 patients had grade 0, 2 grade 1 (pretreatment grades 2 and 3), and 1 grade 3 (pretreatment grade 3) hematuria. Of the 4 patients without prior prostate surgery, 2 had grade 0 (pretreatment grades 1 and 3), and 2 had grade 1 (pretreatment grade 2) hematuria. In summary, 14 of 16 patients improved according to their hematuria grade. We have since added another 10 patients to our study, with a mean follow-up of 11 months. Six of 7 patients who had previous prostatectomies in this group now have grade 0 hematuria. Overall, 8 of the 10 have improved according to hematuria grade. CONCLUSIONS: Long-term follow-up has confirmed the efficacy of finasteride in treating gross hematuria associated with BPH and we now recommend finasteride as first line therapy in the treatment of BPH-associated gross hematuria. reserved.

Aged↗
PubMed1998

Curve matching on brain surfaces using Frenet distances.

This paper describes methods for diffeomorphic matching of curves on brain surfaces. Distances between curves are defined by Frenet representation via speed, curvature, and torsion. The curvematching algorithm is based on bipartite graph matching, with weights defined by the Frenet distance over diffeomorphic maps of one curve onto the other (Sedgewick [1983]: Algorithms). We follow Khaneja ([1996]: Statistics and Geometry of Cortical Features) and define fundus curves on the brain surfaces as extremal curvature lines generated using dynamic programming. Examples are shown for fundus curve matchings on macaque brain surfaces.

Algorithms↗