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Biomedical subjects

M I Miller

Publications and source records attributed to M I Miller.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

An enormous testicular sex cord/gonadal stromal tumor.

Testicular sex cord/gonadal stromal tumors are relatively rare non-germ cell neoplasms. The authors describe an unusual case of an enormous unclassified sex cord/gonadal stromal tumor, which histologically appeared benign. The implications of the pathological findings and the surgical management are discussed.

Adolescent↗

Etiology of voiding dysfunction in men less than 50 years of age.

OBJECTIVES: Chronic lower urinary tract symptoms in young men are often attributed to misdiagnosed chronic nonbacterial prostatitis. The purpose of this study was to analyze etiology of chronic voiding dysfunction in men less than 50 years of age. METHODS: The videourodynamic studies of 137 men 50 years of age or less with chronic voiding dysfunction, performed between January 1990 and October 1995, were retrospectively analyzed. RESULTS: The distribution of urodynamic abnormalities included 74 (54%) patients with primary vesical neck obstruction, 33 (24%) with obstruction localized to membranous urethra (pseudodyssnergia), 23 (17%) with impaired bladder contractility, and the remaining 7 (5%) with an acontractile bladder. Detrusor instability was present in 67 men (49%). CONCLUSIONS: Voiding dysfunction among young men is common and is often misdiagnosed. Videourodynamic evaluation is very useful in establishing the correct diagnosis and ultimately in delivery of appropriate therapy.

Adult↗

Hippocampal MR imaging morphometry by means of general pattern matching.

PURPOSE: To determine the repeatability and validity of a pattern-matching method for the segmentation and measurement of hippocampi on magnetic resonance (MR) images. MATERIALS AND METHODS: Comparable two-dimensional MR images obtained in 18 subjects (nine healthy control subjects [six men, three women; aged 24-54 years] and nine patients with schizophrenia [six men, three women; aged 22-61 years]) were twice segmented manually and twice segmented by using pattern matching with digital atlas transformation. The atlas transformation was accomplished in two steps: global followed by local matching. Global matching was performed with use of landmarks; local matching was performed with use of a viscous fluid model. RESULTS: The mean percentage of difference between two atlas-based measurements was 1.33% +/- 1.23 (+/- standard deviation); that between two manual measurements was 4.67% +/- 4.71. The validity of the atlas transformation measurements was demonstrated by means of the high correlation (intraclass correlation coefficient = .96) with manual segmentation measurements. Schizophrenic hippocampal areas tended to be smaller; however, no differences in hippocampal shape were found between patients with schizophrenia and patients with control subjects. CONCLUSION: General pattern matching of a digital brain atlas to an individual MR image is a mathematically robust method of measurement that is reproducible and less variable than manual measurement.

Adult↗

Model-based maximum-likelihood estimation for phase- and frequency-encoded magnetic-resonance-imaging data.

A maximum-likelihood (ML)-based magnetic-resonance-imaging (MRI) reconstruction algorithm is established, based on frequency- and phase-encoded data. The model on which the ML method is based is a superposition of exponentially decaying, sinc-modulated sinusoids, arising from the basic Bloch equations for MR spectroscopy, modified to account for the distribution of resonance frequencies and phases used for spatial localization in the image field. Spatial-localizing gradients are assumed to be known linear functions of spatial coordinate position, with the x-encode (frequency) gradient applied continuously during the full duration of data collection, and the y-encode (phase) gradient applied during varying time periods before data collection. A single-voxel emitter becomes sinc-modulated in the x, y directions at rates proportional to voxel size and gradient strengths in the x-encode and y-encode directions. The full two-dimensional MRI signal becomes a superposition of sinc-modulated, exponentially decaying, single-sinusoid emitters, one for each voxel. The ML estimation of spin-density and spin-spin relaxation decay time images becomes a nonlinear least-squares optimization problem; it is solved using an iterative expectation-maximization algorithm for estimating multiple modulated sinusoids in noise. Phantom studies are presented, demonstrating the accuracy of the model and the application of the algorithm to spin-density and spin-spin relaxation decay time profiles.

Algorithms↗

Laser tissue soldering in urinary tract reconstruction: first human experience.

OBJECTIVES: Laser tissue soldering (LTS) in the urinary tract provides an immediate leak-free seal and may avoid complications seen with conventional repair (such as fistula and stricture). We have begun a Phase I clinical trial investigating the use of LTS in performing urologic reconstructive surgery. METHODS: Ten patients (aged 3 months to 38 years) underwent urologic reconstruction using LTS with a protein solder composed of human albumin (42%) and indocyanine green dye. In each case standard microsuture repair preceded laser-soldered suture line reinforcement. Anastomotic closure time and immediate leak pressure were measured. Postoperatively, all patients were evaluated for evidence of complications, including stricture, fistula formation, or impaired healing. RESULTS: Using LTS as an adjunct to suturing added an average of 7.9 +/- 3.0 minutes (28%) to the overall mean anastomotic time of 28.3 +/- 9.4 minutes. Intraoperative leak pressure measurements for laser-soldered anastomoses (> or = 94.2 +/- 24.2 mm Hg) were significantly higher (P < 0.001) than primarily sutured anastomoses (20 +/- 2.9 mm Hg). Two instances of suture disruption (20%) occurred during laser activation, neither of which were repaired with sutures. Average follow-up for all patients was 7.1 + - 2.2 months. There were no intraoperative or postoperative complications, including the 2 patients with suture disruption. CONCLUSIONS: These initial clinical results indicate that LTS is safe, easy to perform, and, contrary to conventional suturing, provides an immediate leak-free closure. Follow-up in these and other patients, as well as those undergoing sutureless and stent-free procedures, will determine whether our method of LTS benefits patients undergoing urologic reconstruction.

Anastomosis, Surgical↗

Laser welding versus suturing in tunica vaginalis and venous patch graft corporoplasty.

Congenital penile curvature may result from corporeal disproportion in nearly 40% of cases, while in adults scarring of the corporeal bodies or periurethral fibrosis accounts for the majority of cases. Some surgeons advocate lengthening the fibrosed corporeal bodies by excising tunica albuginea and grafting such defects to straighten the penis. Tunica vaginalis, dermis, dorsal vein and lyophilized dura have been used for this purpose. Traditionally, these graft biomaterials have been sutured to the tunica albuginea. We assessed the feasibility, short-term safety and efficacy of diode laser tissue welding using albumin based solder and indocyanine green dye to perform patch graft corporoplasty in the dog. Ten animals were subjected to bilateral transverse excision of 1 x 2 cm. sections of tunica albuginea. Corporoplasty was performed using grafts composed of saphenous vein (5) or tunica vaginalis (5). Microsurgical repair with 7-zero polydioxanone suture (10) was compared to contralateral laser welded repair (10) by recording operative time, initial and short-term bursting pressures (mean plus or minus standard deviation) and histological analysis. Operative time on the laser side (9.8 +/- 2.3 minutes) was significantly shorter (p < 0.05) than on the suture side (17.1 +/- 5.1 minutes). Leak pressures, initially (laser 105.7 +/- 23.8 mm. Hg versus suture 35.3 +/- 8.0 mm. Hg), at 3 to 5 days (greater than 333.3 +/- 62.4 mm. Hg versus 136.6 +/- 39.4 mm. Hg) and at 7 to 10 days (greater than 397.8 +/- 39.8 mm. Hg versus 191.5 +/- 46.4 mm. Hg) were higher (p < 0.05) in the laser side compared to controls. Graft failure (necrosis) occurred in 3 repairs (2 laser on day 4 and 1 suture on day 10). Viable tissue with minimal differences in foreign body reaction between groups was observed in the remaining grafts. We conclude that laser welded patch graft corporoplasty using tunica vaginalis or vein is easy to perform, and provides excellent initial and short-term leak pressures. The use of laser welding in conjunction with suturing may be beneficial in corporoplasty for congenital or acquired penile curvature.

Animals↗

The effects of finasteride on hematuria associated with benign prostatic hyperplasia: a preliminary report.

PURPOSE: The efficacy of finasteride was assessed in the treatment of gross hematuria associated with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A retrospective review was done of 18 patients who had been placed on finasteride (5 mg . daily) for the treatment of gross hematuria associated with BPH. A hematuria grading system was devised. RESULTS: Of the 12 patients with longer than 3 months of followup (mean 14) 11 improved according to the grade of hematuria after finasteride therapy. CONCLUSIONS: Finasteride is effective in treating hematuria associated with BPH. This finding is especially relevant for patients with multiple medical problems and anesthetic risks.

Aged↗

Massively parallel computers for 3D single-photon-emission computed tomography.

Since the introduction of the expectation-maximization (EM) algorithm for generating maximum-likelihood (ML) and maximum a posteriori (MAP) estimates in emission tomography, there have been many investigators applying the ML method. However, almost all of the previous work has been restricted to two-dimensional (2D) reconstructions. The major focus and contribution of this paper is to demonstrate a fully three-dimensional (3D) implementation of the MAP method for single-photon-emission computed tomography (SPECT). The 3D reconstruction exhibits an improvement in resolution when compared to the generation of the series of separate 2D slice reconstructions. As has been noted, the iterative EM algorithm for 2D reconstruction is highly computational; the 3D algorithm is far worse. To accommodate the computational complexity, we have extended our previous work in the 2D arena and demonstrate an implementation on the class of massively parallel processors of the 3D algorithm. Using a 16000 processor MasPar machine, the algorithm is demonstrated to execute at 1.24 s/EM iteration for the entire 64 x 64 x 64 cube of 64 planar measurements obtained from the Siemens Orbiter rotating camera operating in the high-resolution mode.

Algorithms↗

3D brain mapping using a deformable neuroanatomy.

This paper presents two different mathematical methods that can be used separately or in conjunction to accommodate shape variabilities between normal human neuroanatomies. Both methods use a digitized textbook to represent the complex structure of a typical normal neuroanatomy. Probabilistic transformations on the textbook coordinate system are defined to accommodate shape differences between the textbook and images of other normal neuroanatomies. The transformations are constrained to be consistent with the physical properties of deformable elastic solids in the first method and those of viscous fluids in the second. Results presented in this paper demonstrate how a single deformable textbook can be used to accommodate normal shape variability.

Algorithms↗

Mathematical textbook of deformable neuroanatomies.

Mathematical techniques are presented for the transformation of digital anatomical textbooks from the ideal to the individual, allowing for the representation of the variabilities manifest in normal human anatomies. The ideal textbook is constructed on a fixed coordinate system to contain all of the information currently available about the physical properties of neuroanatomies. This information is obtained via sensor probes such as magnetic resonance, as well as computed axial and emission tomography, along with symbolic information such as white- and gray-matter tracts, nuclei, etc. Human variability associated with individuals is accommodated by defining probabilistic transformations on the textbook coordinate system, the transformations forming mathematical translation groups of high dimension. The ideal is applied to the individual patient by finding the transformation which is consistent with physical properties of deformable elastic solids and which brings the coordinate system of the textbook to that of the patient. Registration, segmentation, and fusion all result automatically because the textbook carries symbolic values as well as multisensor features.

Algorithms↗

A new stochastic model for auditory-nerve discharge.

This paper investigates the mechanisms for history-dependent probability of eight-nerve discharge, which is modeled as the probability that the excitatory postsynaptic potential (EPSP) process crosses afferent membrane threshold, with the discharge history dependence due to the dependence of postsynaptic threshold voltage on time since previous action potential. The model parameters are the Poisson intensity alpha t of vesicle release, the duration epsilon and probability density PV(upsilon) of single-vesicle EPSP's, and the threshold voltage curve theta (tau) for spiking. It is proven that the infinitesimal conditional probabilities of discharge exhibit two distinct behaviors. The first is associated with the time tau = T D, exactly the time the neuron releases from absolute refractory where there is no intensity [theta(tau) = infinity, for tau < T D]. At this time the neuron has a nonzero probability of discharge [symbol:see text] (T D) = lim delta-->0 Pr(Nt,t+delta = 1/t - wNt = T D). The second regime corresponds to the time since previous spike being greater than dead time, tau > T D, during which time the intensity exists lambda t(tau) = lim delta-->0(1/delta) Pr(Nt,t+delta = 1/t - wNt = tau > T D). The fact that there is a nonzero probability of discharge following passage from the absolute refractory period predicts the nonmonotonic hazard intensity seen in high spontaneous neurons [R. P. Gaumond, Ph.D. thesis, Washington University, St. Louis (1980)] and high driven rate neurons. It is shown that for the lowest range of vesicle release intensities where the vesicle-release-rate/membrane-integration-time product alpha t epsilon small, the nonzero probability of discharge at a point is approximately equal to 0. The discharge intensity is dominated by a term linear in vesicle release intensity: lambda t(tau) approximately alpha t exp(-integral of t-epsilon t alpha sigma d sigma) integral of theta (tau) infinity Pv(upsilon)d upsilon. This is precisely the Siebert-Gaumond intensity product form with monotonic recovered discharge probability. At high vesicle release rates, such as for driven rate responses, the nonzero probability of discharging at a point becomes of nonsignificant size, and the intensity of discharge grows nonlinearly with alpha t, implying the product model does not hold. The model is demonstrated via the analysis of auditory nerve fibers from the cat.

Animals↗

Maximum a posteriori estimation with Good's roughness for three-dimensional optical-sectioning microscopy.

The three-dimensional image-reconstruction problem solved here for optical-sectioning microscopy is to estimate the fluorescence intensity lambda(x), where x epsilon R3, given a series of Poisson counting process measurements [Mj(dx)]jJ = 1, each with intensity [formula: see text] with [formula: see text] being the point spread of the optics focused to the jth plane and sj(y) the detection probability for detector point y at focal depth j. A maximum a posteriori reconstruction generated by inducing a prior distribution on the space of images via Good's three-dimensional rotationally invariant roughness penalty [formula: see text] It is proven that the sequence of iterates that is generated by using the expectation maximization algorithm is monotonically increasing in posterior probability, with stable points of the iteration satisfying the necessary maximizer conditions of the maximum a posteriori solution. The algorithms were implemented on the DECmpp-SX, a 64 x 64 parallel processor, running at < 2 s/(64(3), 3-D iteration). Results are demonstrated from simulated as well as amoebae and volvox data. We study performance comparisons of the algorithms for the missing-data problems corresponding to fast data collection for rapid motion studies in which every other focal plane is removed and for imaging with limited detector areas and efficiency.

Algorithms↗