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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
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↗
PubMed1997

Volumetric transformation of brain anatomy.

This paper presents diffeomorphic transformations of three-dimensional (3-D) anatomical image data of the macaque occipital lobe and whole brain cryosection imagery and of deep brain structures in human brains as imaged via magnetic resonance imagery. These transformations are generated in a hierarchical manner, accommodating both global and local anatomical detail. The initial low-dimensional registration is accomplished by constraining the transformation to be in a low-dimensional basis. The basis is defined by the Green's function of the elasticity operator placed at predefined locations in the anatomy and the eigenfunctions of the elasticity operator. The high-dimensional large deformations are vector fields generated via the mismatch between the template and target-image volumes constrained to be the solution of a Navier-Stokes fluid model. As part of this procedure, the Jacobian of the transformation is tracked, insuring the generation of diffeomorphisms. It is shown that transformations constrained by quadratic regularization methods such as the Laplacian, biharmonic, and linear elasticity models, do not ensure that the transformation maintains topology and, therefore, must only be used for coarse global registration.

Animals↗
PubMed1997

Three-dimensional hippocampal MR morphometry with high-dimensional transformation of a neuroanatomic atlas.

PURPOSE: To test automated three-dimensional magnetic resonance (MR) imaging morphometry of the human hippocampus, to determine the potential gain in precision compared with conventional manual morphometry. MATERIAL AND METHODS: A canonical three-dimensional MR image atlas was used as a deformable template and automatically matched to three-dimensional MR images of 10 individuals (five healthy and five schizophrenic subjects). A subvolume containing the hippocampus was defined by using 16 landmarks that constrained the automated search for hippocampal boundaries. Transformation of the hippocampus template was automatically performed by using global pattern matching through a sequence of low-then high-dimensional translations, rotations, and scalings. RESULTS: The average test-retest volume difference measured with the automatic method was 3.1%, compared with the manual test-retest difference of 7.1%. Correlation between automated and manually determined volumes demonstrated the validity of the automated technique (intraclass correlation coefficient = .86). CONCLUSION: The automated method estimates hippocampal volumes with less variability (ie, lower variance) than that of manual out-lining.

Adult↗
PubMed1997

Stochastic threshold characterization of the intensity of active channel dynamical action potential generation.

Stochastic threshold characterization of the intensity of active channel dynamical action potential generation. J. Neurophysiol. 78: 2616-2630, 1997. This paper develops a stochastic intensity description for action potential generation formulated in terms of stochastic processes, which are direct analogues of the physiological processes of the pre- and postsynaptic complex of the cochlear nerve: 1) neurotransmitter release is modeled as an inhomogeneous Poisson counting process with release intensity mu t, 2) the excitatory postsynaptic conductance (EPSC) process is modeled as a marked, linearly filtered Poisson process resulting from the linear superposition of standard shaped postsynaptic conductances of size G, and 3) action potential generation is modeled as resulting from the EPSC exceeding a random threshold determined by active channel dynamics of the Hodgkin-Huxley type. The random threshold is defined to be the least upper bound in the size of a standard-shaped neurotransmitter release injected at time t given the previous action potential time and the number of releases occurring in a short preconditioning time increment. The action potential process is modeled as a self-exciting point process with stochastic intensity resulting from the probability that the random threshold process crosses the threshold in some small time increment that is a function of time since previous action potential, release intensity, and the probability that a single synaptic event exceeds the stochastic threshold. The stochastic intensity model is consistent with a direct simulation of the nonlinear Hodgkin-Huxley differential equations over a variety of parameters for the vesicle release intensity, vesicle size, vesicle duration, and temperatures. Results are presented showing that the regularity properties seen in the vestibular primary afferent in the lizard, Calotes versicolor, associated with a slow-to-activate potassium channel resulting in a long afterhyperpolarization can be accommodated directly by the stochastic intensity description. The stimulus dependence of the model is attributed to synaptic transmission and the probabilistic nature to the threshold conductance process, which is dependent upon the EPSC process. The stochastic intensity is seen to have a form consistent with the phenomenologically based Siebert-Gaumond model, a stimulus-related function of time multiplied by a refractory-related function of time since previous action potential.

Action Potentials↗
PubMed1997

Apoptosis in the rat penis after penile denervation.

PURPOSE: Despite the advances in nerve sparing prostatectomy for prostate cancer, some patients develop impotence or subjectively complain of a decrease in penile size. We hypothesized that these clinical observations may be explained by injury to the cavernous nerves resulting in programmed cell death (apoptosis) within the penis. We utilized a rat model of penile denervation in order to demonstrate apoptosis after denervation. METHODS AND MATERIALS: Fifteen male Sprague Dawley rats underwent abdominal exploration and bilateral cavernous neurotomy. Fifteen sham operations were performed as normal controls. The rats were sacrificed on postoperative day 1,2,3,6, and 10 and their penises were harvested. Messenger RNA was extracted and probed on a northern blot for sulfated glycoprotein-2 (SGP-2). SGP-2 is a gene product reported to be elevated in apoptotic tissues. Separate denervated and sham rats were used for DNA extraction (sacrificed postoperative day #2) in order to demonstrate the internucleosomal DNA fragmentation (laddering) found in apoptotic tissues. In addition, in situ histology was performed with ISEL techniques (in situ end labeling) to stain for apoptotic nuclei in denervated rats. RESULTS: Northern blot analysis showed a large increase in SGP-2 mRNA expression in the denervated rats with little detected in the sham operated group. DNA extraction studies revealed the presence of internucleosomal DNA fragmentation on agarose gel (a marker for apoptosis) in the denervated group versus intact high molecular weight DNA in the sham rats. In addition, in situ staining of denervated penile erectile tissue demonstrated apoptotic nuclei in the cavernous tissue. CONCLUSION: Apoptosis of penile erectile tissue occurs after denervation of the rat penis. This has not been previously described in the literature and may offer some explanation at the molecular level concerning the mechanism of impotence and/or decrease in penile size after radical prostatectomy.

Animals↗