Isomer-selected ion-molecule reactions of acetylene cations with propyne and allene.

One of the fundamental goals of chemistry is to determine how molecular structure influences interactions and leads to different reaction products. Studies of isomer-selected and resolved chemical reactions can shed light directly on how form leads to function. In the following, we present the results of gas-phase reactions between acetylene cations (C2D2+) with two different isomers of C3H4: propyne (DC3D3) and allene (H2C3H2). Our highly controlled, trapped-ion environment allows for precise determination of reaction products and kinetics. From these results, we can infer details of the underlying reaction dynamics of C2H2+ + C3H4. Through the synergy of experimental results and high-level quantum chemical potential energy surface calculations, we are able to identify distinct reaction mechanisms for the two isomers. We find long-range charge exchange with no complex formation is favored for allene, whereas charge exchange leads to an intermediate reaction complex for propyne and thus, different products. Therefore, this reaction displays a pronounced isomer-selective bi-molecular reactive process.

An ion trap time-of-flight mass spectrometer with high mass resolution for cold trapped ion experiments.

Trapping molecular ions that have been sympathetically cooled with laser-cooled atomic ions is a useful platform for exploring cold ion chemistry. We designed and characterized a new experimental apparatus for probing chemical reaction dynamics between molecular cations and neutral radicals at temperatures below 1 K. The ions are trapped in a linear quadrupole radio-frequency trap and sympathetically cooled by co-trapped, laser-cooled, atomic ions. The ion trap is coupled to a time-of-flight mass spectrometer to readily identify product ion species and to accurately determine trapped ion numbers. We discuss, and present in detail, the design of this ion trap time-of-flight mass spectrometer and the electronics required for driving the trap and mass spectrometer. Furthermore, we measure the performance of this system, which yields mass resolutions of m/Δm ≥ 1100 over a wide mass range, and discuss its relevance for future measurements in chemical reaction kinetics and dynamics.

Analysis of cortical morphometric variability using labeled cortical distance maps.

Morphometric (i.e., shape and size) differences in the anatomy of cortical structures are associated with neurodevelopmental and neuropsychiatric disorders. Such differences can be quantized and detected by a powerful tool called Labeled Cortical Distance Map (LCDM). The LCDM method provides distances of labeled gray matter (GM) voxels from the GM/white matter (WM) surface for specific cortical structures (or tissues). Here we describe a method to analyze morphometric variability in the particular tissue using LCDM distances. To extract more of the information provided by LCDM distances, we perform pooling and censoring of LCDM distances. In particular, we employ Brown-Forsythe (BF) test of homogeneity of variance (HOV) on the LCDM distances. HOV analysis of pooled distances provides an overall analysis of morphometric variability of the LCDMs due to the disease in question, while the HOV analysis of censored distances suggests the location(s) of significant variation in these differences (i.e., at which distance from the GM/WM surface the morphometric variability starts to be significant). We also check for the influence of assumption violations on the HOV analysis of LCDM distances. In particular, we demonstrate that BF HOV test is robust to assumption violations such as the non-normality and within sample dependence of the residuals from the median for pooled and censored distances and are robust to data aggregation which occurs in analysis of censored distances. We recommend HOV analysis as a complementary tool to the analysis of distribution/location differences. We also apply the methodology on simulated normal and exponential data sets and assess the performance of the methods when more of the underlying assumptions are satisfied. We illustrate the methodology on a real data example, namely, LCDM distances of GM voxels in ventral medial prefrontal cortices (VMPFCs) to see the effects of depression or being of high risk to depression on the morphometry of VMPFCs. The methodology used here is also valid for morphometric analysis of other cortical structures.

Macro- and microstructural changes in patients with spinocerebellar ataxia type 6: assessment of phylogenetic subdivisions of the cerebellum and the brain stem.

BACKGROUND AND PURPOSE: Site-specific degeneration patterns of the infratentorial brain in relation to phylogenetic origins may relate to symptoms in patients with spinocerebellar degeneration, but the patterns are still unclear. We investigated macro- and microstructural changes of the infratentorial brain based on phylogenetic origins and their correlation with symptoms in patients with spinocerebellar ataxia type 6. MATERIALS AND METHODS: MR images of 9 patients with spinocerebellar ataxia type 6 and 9 age- and sex-matched controls were obtained. We divided the infratentorial brain on the basis of phylogenetic origins and performed an atlas-based analysis. Comparisons of the 2 groups and a correlation analysis assessed with the International Cooperative Ataxia Rating Scale excluding age effects were performed. RESULTS: A significant decrease of fractional volume and an increase of mean diffusivity were seen in all subdivisions of the cerebellum and in all the cerebellar peduncles except mean diffusivity in the inferior cerebellar peduncle in patients compared with controls (P < .0001 to <.05). The bilateral anterior lobes showed the strongest atrophy. Fractional volume decreased mainly in old regions, whereas mean diffusivity increased mainly in new regions of the cerebellum. Reflecting this tendency, the International Cooperative Ataxia Rating Scale total score showed strong correlations in fractional volume in the right flocculonodular lobe and the bilateral deep structures and in mean diffusivity in the bilateral posterior lobes (r = 0.73 to ±0.87). CONCLUSIONS: We found characteristic macro- and microstructural changes, depending on phylogenetic regions of the infratentorial brain, that strongly correlated with clinical symptoms in patients with spinocerebellar ataxia type 6.

The development of a population of 4D pediatric XCAT phantoms for imaging research and optimization.

PURPOSE: We previously developed a set of highly detailed 4D reference pediatric extended cardiac-torso (XCAT) phantoms at ages of newborn, 1, 5, 10, and 15 yr with organ and tissue masses matched to ICRP Publication 89 values. In this work, we extended this reference set to a series of 64 pediatric phantoms of varying age and height and body mass percentiles representative of the public at large. The models will provide a library of pediatric phantoms for optimizing pediatric imaging protocols. METHODS: High resolution positron emission tomography-computed tomography data obtained from the Duke University database were reviewed by a practicing experienced radiologist for anatomic regularity. The CT portion of the data was then segmented with manual and semiautomatic methods to form a target model defined using nonuniform rational B-spline surfaces. A multichannel large deformation diffeomorphic metric mapping algorithm was used to calculate the transform from the best age matching pediatric XCAT reference phantom to the patient target. The transform was used to complete the target, filling in the nonsegmented structures and defining models for the cardiac and respiratory motions. The complete phantoms, consisting of thousands of structures, were then manually inspected for anatomical accuracy. The mass for each major tissue was calculated and compared to linearly interpolated ICRP values for different ages. RESULTS: Sixty four new pediatric phantoms were created in this manner. Each model contains the same level of detail as the original XCAT reference phantoms and also includes parameterized models for the cardiac and respiratory motions. For the phantoms that were 10 yr old and younger, we included both sets of reproductive organs. This gave them the capability to simulate both male and female anatomy. With this, the population can be expanded to 92. Wide anatomical variation was clearly seen amongst the phantom models, both in organ shape and size, even for models of the same age and sex. The phantoms can be combined with existing simulation packages to generate realistic pediatric imaging data from different modalities. CONCLUSIONS: This work provides a large cohort of highly detailed pediatric phantoms with 4D capabilities of varying age, height, and body mass. The population of phantoms will provide a vital tool with which to optimize 3D and 4D pediatric imaging devices and techniques in terms of image quality and radiation-absorbed dose.

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.

Multiple myeloma presenting with primary meningococcal arthritis.

A 64-year-old white man presented with Neisseria meningitidis primary septic arthritis. Further evaluation revealed multiple myeloma. Increased susceptibility to infection occurs early in multiple myeloma; thus, a rare cause of primary septic arthritis, such as N. meningitidis, warrants a full evaluation for immunocompromise.

A personal computer based implementation of the maximum-likelihood method of analysis of electron microscope autoradiographs.

The maximum-likelihood (ML) method for the quantitative analysis of electron-microscopic autoradiographs has been shown to be substantially superior to the conventional crossfire (CF) method. It can generate reliable and accurate tracer concentration estimates with far fewer micrographs and produce valid estimates even at counts low enough to preclude the use of the crossfire method while eliminating the need for special ad hoc treatment of narrow membranous structures as well as the secondary verification of the tracer concentration estimates. Despite these significant advantages, the large computational requirements of the ML method has to date hampered its widespread use. In this paper, we present a new line-integration method that allows us to reduce the computational requirements of the ML method to a point where it becomes feasible to implement it on a small computer system of the type typically available to a laboratory user of EM autoradiography. We present the complete line-integration method for the particular case of EM autoradiography with tritium, and show how it can be adapted to other isotopes. We have constructed a software package that implements the complete maximum-likelihood method on the IBM PC class of machines using our line-integration method. Features of this software package which are of particular importance to the research community are device independence, which makes it usable with a large variety of currently available laboratory equipment, and easy portability of the software and data between different computer systems.

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.

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.

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.

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.

Maximum a posteriori estimation for SPECT using regularization techniques on massively parallel computers.

Single photon emission computed tomography (SPECT) reconstructions performed using maximum a posteriori (penalized likelihood) estimation with the expectation maximization algorithm are discussed. Due to the large number of computations, the algorithms were performed on a massively parallel single-instruction multiple-data computer. Computation times for 200 iterations, using I.J. Good and R.A. Gaskins's (1971) roughness as a rotationally invariant roughness penalty, are shown to be on the order of 5 min for a 64x64 image with 96 view angles on an AMT-DAP 4096 processor machine and 1 min on a MasPar 4096 processor machine. Computer simulations performed using parameters for the Siemens gamma camera and clinical brain scan parameters are presented to compare two regularization techniques-regularization by kernel sieves and penalized likelihood with Good's rotationally invariant roughness measure-to filtered backprojection. Twenty-five independent sets of data are reconstructed for the pie and Hoffman brain phantoms. The average variance and average deviation are examined in various areas of the brain phantom. It is shown that while the geometry of the area examined greatly affects the observed results, in all cases the reconstructions using Good's roughness give superior variance and bias results to the two alternative methods.

3-D maximum a posteriori estimation for single photon emission computed tomography on massively-parallel computers.

A fully three-dimensional (3-D) implementation of the maximum a posteriori (MAP) method for single photon emission computed tomography (SPECT) is demonstrated. The 3-D reconstruction exhibits a major increase in resolution when compared to the generation of the series of separate 2-D slice reconstructions. As has been noted, the iterative EM algorithm for 2-D reconstruction is highly computational; the 3-D algorithm is far worse. To accommodate the computational complexity, previous work in the 2-D arena is extended, and an implementation on the class of massively parallel processors of the 3-D algorithm is demonstrated. Using a 16000- (4000-) processor MasPar/DECmpp-Sx machine, the algorithm is demonstrated to execute at 2.5 (7.8) s/EM-iteration for the entire 64x64x64 cube of 96 planar measurements obtained from the Siemens Orbiter rotating camera operating in the high-resolution mode.

Maximum likelihood SPECT in clinical computation times using mesh-connected parallel computers.

Extending the work of A.W. McCarthy et al. (1988) and M.I. Miller and B. Roysam (1991), the authors demonstrate that a fully parallel implementation of the maximum-likelihood method for single-photon emission computed tomography (SPECT) can be accomplished in clinical time frames on massively parallel systolic array processors. The authors show that for SPECT imaging on 64x64 image grids, with 96 view angles, the single-instruction, multiple data (SIMD) distributed array processor containing 64(2) processors performs the expectation-maximization (EM) algorithm with Good's smoothing at a rate of 1 iteration/1.5 s. This promises for emission tomography fully Bayesian reconstructions including regularization in clinical computation times which are on the order of 1 min/slice. The most important result of the implementations is that the scaling rules for computation times are roughly linear in the number of processors.

Parallel algorithms for maximum a posteriori estimation of spin density and spin-spin decay in magnetic resonance imaging.

A maximum a posteriori (MAP) algorithm is presented for the estimation of spin-density and spin-spin decay distributions from frequency and phase-encoded magnetic resonance imaging data. Linear spatial localization gradients are assumed: the y-encode gradient applied during the phase preparation time of duration tau before measurement collection, and the x-encode gradient applied during the full data collection time t>/=0. The MRI signal model developed in M.I. Miller et al., J. Magn. Reson., ser. B (Apr. 1995) is used in which a signal resulting from M phase encodes (rows) and N frequency encode dimensions (columns) is modeled as a superposition of MN sinc-modulated exponentially decaying sinusoids with unknown spin-density and spin-spin decay parameters. The nonlinear least-squares MAP estimate of the spin density and spin-spin decay distributions solves for the 2MN spin-density and decay parameters minimizing the squared-error between the measured data and the sine-modulated exponentially decay signal model using an iterative expectation-maximization algorithm. A covariance diagonalizing transformation is derived which decouples the joint estimation of MN sinusoids into M separate N sinusoid optimizations, yielding an order of magnitude speed up in convergence. The MAP solutions are demonstrated to deliver a decrease in standard deviation of image parameter estimates on brain phantom data of greater than a factor of two over Fourier-based estimators of the spin density and spin-spin decay distributions. A parallel processor implementation is demonstrated which maps the N sinusoid coupled minimization to separate individual simple minimizations, one for each processor.

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.

An evaluation of maximum likelihood reconstruction for SPECT.

A reconstruction method for SPECT (single photon emission computerized tomography) that uses the maximum likelihood (ML) criterion and an iterative expectation-maximization (EM) algorithm solution is examined. The method is based on a model that incorporates the physical effects of photon statistics, nonuniform photon attenuation, and a camera-dependent point-spread response function. Reconstructions from simulation experiments are presented which illustrate the ability of the ML algorithm to correct for attenuation and point-spread. Standard filtered backprojection method reconstructions, using experimental and simulated data, are included for reference. Three studies were designed to focus on the effects of noise and point-spread, on the effect of nonuniform attenuation, and on the combined effects of all three. The last study uses a chest phantom and simulates Tl-201 imaging of the myocardium. A quantitative analysis of the reconstructed images is used to support the conclusion that the ML algorithm produces reconstructions that exhibit improved signal-to-noise ratios, improved image resolution, and image quantifiability.

Noise and edge artifacts in maximum-likelihood reconstructions for emission tomography.

Images produced in emission tomography with the expectation-maximization algorithm have been observed to become more noisy and to have large distortions near edges as iterations proceed and the images converge towards the maximum-likelihood estimate. It is our conclusion that these artifacts are fundamental to reconstructions based on maximum-likelihood estimation as it has been applied usually; they are not due to the use of the expectation-maximization algorithm, which is but one numerical approach for finding the maximum-likelihood estimate. In this paper, we develop a mathematical approach for suppressing both the noise and edge artifacts by modifying the maximum-likelihood approach to include constraints which the estimate must satisfy.

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.