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PubMed2005

White matter fiber tracts of the human brain: three-dimensional mapping at microscopic resolution, topography and intersubject variability.

The position and extent of individual fiber tracts within the white matter of human brains can be identified in vivo using diffusion tensor imaging (DTI) and fiber tracking methods. Previous to this study, however, the lack of three-dimensional (3-D) probability maps precluded comparing the anatomical precision of MRI studies with microscopically defined fiber tracts in human postmortem brains. The present study provides 3-D registered maps of the topography, course and intersubject variability of major fiber tracts, which were identified at microscopic resolution. The analyzed tracts include the corticospinal tract, optic and acoustic radiations, fornix, cingulum, corpus callosum, superior longitudinal, superior and inferior occipito-frontal and uncinate fascicles; sources and targets of fiber tracts include the lateral and medial geniculate nuclei and mamillary bodies. Tracts and nuclei were identified in serial myelin-stained histological sections of ten postmortem brains. The sections were 3-D reconstructed and registered to a standardized stereotaxic space of an in vivo MR reference brain by means of linear and non-linear, elastic transformations. The individual fiber tracts and nuclei were superimposed in the reference space, and probability maps were generated as a quantitative measure of intersubject variability for each voxel of the stereotaxic space. This study presents the first stereotaxic atlas of the course, location and extent of fiber tracts and related nuclei based on microscopically defined localization and topographic data taken at multiple levels on each of the three orthogonal planes. The maps are useful for evaluating and identifying fiber bundles in DTI, for localizing subcortical lesions visible in anatomical MR images and for studying neuronal connectivity.

Adult↗

PubMed2006

Effect of docosahexaenoic acid on tissue targeting and metabolism of plasma lipoproteins.

We examined the effect of the docosahexaenoic acid (DHA) content of lipoproteins on their metabolism in vivo by a radioisotope labeling and tracking method. Purified HDL and LDL were labeled with (3)H-cholesteryl oleate tracer. To mimic dietary-related changes in fatty acid composition of lipoproteins, we incorporated lipids acylated with either DHA, arachidonic (AA) or oleic (OA) acid to phosphatidylcholine (didocosahexaenoylphosphatidylcholine (di22:6-PC), diarachidonoylphosphatidylcholine (di20:4-PC) and dioleoylphosphatidylcholine (di18:0-PC), respectively) into the purified particles. The lipids, at the amount added, did not cause detectable alterations in the morphology of the lipoproteins. Levels of radiotracers in blood and in several target tissues such as brain, heart, liver, muscle and adipose were determined at 1.5, 3 and 24h after intravenous injection into C57Bl/6J mice. No statistically significant differences were detected in the tissue distribution of tracers introduced into HDL enriched in DHA, compared to particles enriched with OA. In contrast, we found a significantly higher proportion of radiolabel associated with LDL enriched in DHA in heart, brown adipose and brain tissues. The uptake of labels associated with DHA containing LDL nearly doubled for heart and brown adipose tissues at 1.5 and 3h, and it was 30% higher for brain tissues at 24h. The tissue distribution of labels from the same particles enriched in AA or OA did not show a statistically significant difference from unaltered control lipoproteins. These findings point to the possible role of DHA in the regulation of LDL metabolism and involvement of the lipoproteins in transport of n-3 PUFA to target organs.

Adipose Tissue, Brown↗

PubMed1991

Single particle tracking. Analysis of diffusion and flow in two-dimensional systems.

Analysis of the trajectories of small particles at high spatial and temporal resolution using video enhanced contrast microscopy provides a powerful approach to characterizing the mechanisms of particle motion in living cells and in other systems. We present here the theoretical basis for the analysis of these trajectories for particles undergoing random diffusion and/or systematic transport at uniform velocity in two-dimensional systems. The single particle tracking method, based on observations of the trajectories of individual particles, is compared with methods that characterize the motions of a large collection of particles such as fluorescence photobleaching recovery. Determination of diffusion coefficients or transport velocities either from correlation of positions or of velocities of the particles is discussed. A result of practical importance is an analysis of the dependence of the expected statistical uncertainty of these determinations on the number of position measurements. This provides a way of judging the accuracy of the diffusion coefficients and transport velocities obtained using this approach.

Diffusion↗

PubMed2003

Measuring the mechanical stress induced by an expanding multicellular tumor system: a case study.

Rapid volumetric growth and extensive invasion into brain parenchyma are hallmarks of malignant neuroepithelial tumors in vivo. Little is known, however, about the mechanical impact of the growing brain tumor on its microenvironment. To better understand the environmental mechanical response, we used multiparticle tracking methods to probe the environment of a dynamically expanding, multicellular brain tumor spheroid that grew for 6 days in a three-dimensional Matrigel-based in vitro assay containing 1.0-microm latex beads. These beads act as reference markers for the gel, allowing us to image the spatial displacement of the tumor environment using high-resolution time-lapse video microscopy. The results show that the volumetrically expanding tumor spheroid pushes the gel outward and that this tumor-generated pressure propagates to a distance greater than the initial radius of the tumor spheroid. Intriguingly, beads near the tips of invasive cells are displaced inward, toward the advancing invasive cells. Furthermore, this localized cell traction correlates with a marked increase in total invasion area over the observation period. This case study presents evidence that an expanding microscopic tumor system exerts both significant mechanical pressure and significant traction on its microenvironment.

Brain↗

PubMed1999

Adapting to expansion increases perceived time-to-collision.

We used a tracking method to measure errors in estimating absolute time-to-collision caused by adapting to an expanding target. After adaptation, the estimated time-to-collision was longer than in the baseline condition. This was the case whether estimates were based on binocular information alone or monocular information alone. Estimates of time-to-collision were lengthened by 8-16% when based on binocular information alone, and by 18-25% when based on monocular information alone. These findings are consistent with a previous proposal that changing-size and changing-disparity information converge before the stage at which motion-in-depth signals are generated.

Adaptation, Psychological↗

PubMed2005

New developments in perfusion imaging by bolus tracking.

The author describes the theoretical basis of quantification of cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) by the bolus tracking method: i.e.dynamic susceptibility contrast MRI using very rapid imaging to capture the first pass of intravenously injected paramagnetic contrast agent.

Blood Volume↗

PubMed1993

Histopathologic findings in congenital grouped pigmentation of the retina.

BACKGROUND: Congenital grouped pigmentation of the retina is a condition characterized by multiple, well-circumscribed, flat, pigmented fundus lesions clustered in a fashion resembling "bear tracks." METHODS: Light and electron microscopy was used to study these lesions in an eye of a 2-year-old boy. The eye was enucleated for retinoblastoma. RESULTS: Similar to the classic, solitary, congenital hypertrophy of the retinal pigment epithelium (CHRPE), the involved RPE cells contained an increased number of large pigment granules. Unlike CHRPE, most pigment granules retained the normal ellipsoidal shape. In addition, hypertrophy and hyperplasia of the RPE cells were not significant features by light and electron microscopy. CONCLUSION: Although the lesions in this case superficially resembled CHRPE by light microscopy, ultrastructural differences were identified.

Child, Preschool↗

PubMed1992

Facilitation of agonist motoneurons upon initiation of rapid and slow voluntary movements in man.

The time course of facilitation of the agonist motoneurons upon initiation of voluntary ankle dorsiflexion was investigated in eight healthy subjects. The H-reflex and visually guided tracking methods were used for testing the excitability of the motoneuron pool and for controlling the initiation of movement as well as speed and force. Since the onset of voluntary EMG activity (EMG reaction time: EMGvRT) was delayed and/or obscured by test H-reflexes which were evoked very close to the behavioral responses, the subject was instructed to make response movements bilaterally, and EMGvRT was measured on the side without stimulation. In every subject, the EMGvRT was invariably longer in the ramp movement than in the step movement. The onset of H-reflex facilitation prior to EMG onset, which was regarded as indicating the arrival time of the descending motor command to the motoneuron pool, always started earlier in the ramp movement than in the step movement. The difference in facilitation onset between the two tasks was smaller than that in EMGvRT. Since the amplitude of the H-reflex at the onset of the voluntary EMG was equivalent in both movements, the development of H-reflex towards the behavioral EMG onset was more gradual in the ramp movement than in the step movement. The present results demonstrate that the longer reaction time in the slow ramp task depends on 2 factors: delay in the arrival of descending facilitatory impulses to the agonist motoneuron pool, and its slow recruitment thereafter.

Adult↗

PubMed2000

Molecular markers for the identification and global tracking of whitefly vector-Begomovirus complexes.

Recent unprecedented upsurges in populations of the whitefly Bemisia tabaci (Genn.) have drawn much attention to its worldwide importance as an insect pest and as the vector of emergent begomoviruses (Family: Geminiviridae; Genus: Begomovirus). Several begomoviruses that are considered 'new' and others previously regarded as minor pathogens have been linked to recent epidemics. Recent studies have revealed much variation in begomoviruses, despite the view that DNA-containing viruses do not rapidly accumulate mutations. Also, certain B. tabaci 'variants' are known that more effectively or selectively transmit certain begomoviruses and exhibit biotic differences that may influence their spread. Patterns of distribution and dissemination of begomoviruses transmitted by B. tabaci are poorly understood because standardized molecular-based tracking methods have not been available. Understanding virus/whitefly vector/host plant interrelationships in the context of emerging problems can be achieved only by linking predicted evolutionary histories with epidemiology using molecular phylogenetic approaches. Identification and validation of informative molecular sequences are essential initial steps in this process. Genus-wide degenerate polymerase chain reaction (PCR) primers have been developed to amplify and sequence the 'core' region of the coat protein open reading frame (ORF) (V1), permitting 'universal' detection and provisional virus identification by comparisons with described viral genotypes. In subsequent studies reported here, several potentially informative viral ORFs and a non-coding region are explored. Of particular use for expanding diversity studies are group- or virus-specific sequences that can be targeted by utilizing newly available core CP sequences, or additional conserved regions around which broad spectrum primers can be designed to target variable sequences in key ORFs or non-coding regions. Prospective markers under exploration were selected with a basis in the most highly conserved viral ORFs, CP (V1) and a portion of replication-associated protein (REP) (L1/C1), and a key non-coding sequence that contain sufficient variability and/or virus-specific sequences, and are consequently of potential epidemiological relevance. Because B. tabaci occurs as a cryptic species, or species complex, that exhibits biotic polymorphism, yet morphological invariance, traditional morphologically based identification is impossible. An overriding complication to establishing molecular markers for identifying whitefly vector variants is that whitefly sequences in general, have not been available. However, recent work has shown that a partial mitochondria cytochrome oxidase I (mt COI) sequence separates vector variants with a basis in geographical origin, suggesting it is useful for further exploring variability and the phylogenetic history of whiteflies on a large scale. Here, the utility of whitefly mt COI nucleotides (nt) sequences is illustrated for inferring relationships between B. tabaci collected from major world regions. Used collectively, these approaches permit investigations of the patterns of distribution and dissemination of begomovirus-whitefly vector complexes for the first time. Ultimately, more immediate recognition of exotic viruses and whitefly vectors and early detection of upsurges in vector populations and of emerging viruses will be possible.

Amino Acid Sequence↗

PubMedDate not supplied

Radionuclide transport simulation and uncertainty analyses with the saturated-zone site-scale model at Yucca Mountain, Nevada.

Evaluation of radionuclide transport in the saturated zone (SZ) to the accessible environment is an important component of performance assessment for the proposed radioactive waste repository at Yucca Mountain. Simulations of radionuclide migration in the SZ have been performed using the calibrated three-dimensional (3-D) SZ site-scale flow and transport model. An innovative particle-tracking method was used to simulate transport that includes the processes of advection, dispersion, matrix diffusion, and sorption. The uncertainties in groundwater flow and radionuclide transport were quantitatively evaluated to develop uncertainty distributions for key model parameters, and multiple realizations of the SZ system were simulated using the SZ site-scale model. The results of multiple realizations of radionuclide transport indicate significant aggregate uncertainty in transport times through the SZ. The simulated radionuclide mass breakthrough curves in the SZ have been coupled with other components of the repository system in Total System Performance Assessment (TSPA) analyses and constitute the means by which uncertainty in the SZ is incorporated into regulatory analyses. Regression analysis has been used to determine the sensitivity of radionuclide transport simulation results to the uncertainty of individual model input parameters. Results of the sensitivity analysis indicate that median radionuclide transport times were dominantly controlled by uncertainty in the specific discharge in the SZ, with sorption and retardation in the alluvium playing important roles for some radionuclides.

Forecasting↗

PubMedDate not supplied

Performance assessment model development and analysis of radionuclide transport in the unsaturated zone, Yucca Mountain, Nevada.

This paper describes the development and use of a particle-tracking model to perform radionuclide-transport simulations in the unsaturated zone at Yucca Mountain, Nevada. The goal of the effort was to produce a computational model that can be coupled to the project's calibrated 3D site-scale flow model so that the results of that effort could be incorporated directly into the Total System Performance Assessment (TSPA) analyses. The transport model simulates multiple species (typically 20 or more) with complex time-varying and spatially varying releases from the potential repository. Water-table rise, climate-change scenarios, and decay chains are additional features of the model. A cell-based particle-tracking method was employed that includes a dual-permeability formulation, advection, longitudinal dispersion, matrix diffusion, and colloid-facilitated transport. This paper examines the transport behavior of several key radionuclides through the unsaturated zone using the calibrated 3D unsaturated flow fields. Computational results illustrate the relative importance of fracture flow, matrix diffusion, and lateral diversion on the distribution of travel times from the simulated repository to the water table for various climatic conditions. Results also indicate rapid transport through fractures for a portion of the released mass. Further refinement of the model will address several issues, including conservatism in the transport model, the assignment of parameters in the flow and transport models, and the underlying assumptions used to support the conceptual models of flow and transport in the unsaturated zone at Yucca Mountain.

Calibration↗

PubMed2001

Myocardial rapid velocity distribution.

Myocardial motion exhibits frequency components of up to 100 Hz, as found by a phased tracking method. To simultaneously measure the rapid and minute velocity signals at multiple points along the surface of the left ventricle (LV), in this study, conventional ultrasonic diagnosis equipment was modified to allow 10 scan lines from a sector scanner to be arbitrarily selected in real-time for analysis. By considering the maximum value of the velocity in the heart wall and the maximum depth from the chest surface, the number of transmission directions of the ultrasonic pulses should be carefully confirmed to be 10 to avoid aliasing, which is much less than the number employed in conventional tissue Doppler imaging (TDI). By applying the system, the velocity signals at about 240 points in the heart walls were simultaneously measured for three healthy volunteers. During a short period of 35 ms around end-diastole, the velocity signals varied spatially in the heart wall. At the end of systole, in the wavelets near the base of the interventricular septum (IVS), the slow pulse continued for about 30 ms, just before the radiation timing of the second heart sound. Then, a steep pulse occurred just at the timing of the closure of the aortic valve. The steep pulse at the base preceded that at the apex by several ms. By Fourier transforming each wavelet, the spatial distribution of the phase of the steep pulse components were clearly displayed. By applying the measurement method to two patients with aortic stenosis (AS), irregular vibration signals, which correspond to the murmur of the heart sound, could be directly detected during the ejection period. In conventional TDI, only the large slow movements due to the heartbeat are displayed, but these rapid and minute velocity components cannot be displayed. In this study, moreover, the phase components were detected for the first time from each of the velocity signals simultaneously measured at multiple points along the 10 scan lines. This measurement and method of analysis offer potential for new diagnostic techniques in cardiac dysfunction.

Aged↗

PubMed2002

Auditory temporal gap detection for noise markers with partially overlapping and non-overlapping spectra.

Temporal gap detection thresholds were obtained from six listeners using an adaptive tracking method and constant spectrum-level noises. In separate blocks of trials, the markers bounding the gap were systematically varied in their spectral overlap or separation (expressed in equivalent rectangular bandwidths, ERBs). In the same listeners, gap thresholds were also obtained for noises of the same bandwidths as those constituting the overlap in the overlap conditions (in the presence of a wideband notched noise masker: 'mask' conditions). For the spectral overlap/separation conditions, gap thresholds were a systematic, linear function of spectral dissimilarity in four of six listeners. In the mask conditions, gap thresholds were inversely related to bandwidth in all listeners. For the three-, four- and five-ERB conditions, gap thresholds in the same listeners for the spectral overlap conditions were higher than those for mask stimuli with the same available within-channel bandwidth and spectrum levels. These data suggest that the spectral dissimilarity between the markers over-rode the availability of within-channel information in the recovery of the temporal gap.

Adult↗

PubMed2004

Basal nitric oxide production contributes to membrane potential and vasotone regulation of guinea pig in vitro spiral modiolar artery.

Nitric oxide (NO) is a potent vasodilating agent implicated in cochlear blood flow regulation. We recently demonstrated that exogenously applied NO donor DPTA-NONOate hyperpolarizes both endothelial and smooth muscle cells of in vitro spiral modiolar artery (SMA) via activation of ATP-sensitive K+ channels (K(ATP)). Also, NO was detected in the SMA cells by NO indicator dye in the in vitro basal condition. Using intracellular recording techniques, electrochemical NO-sensing measurement, and a vaso-diameter video tracking method, we investigated the basal release of NO from the in vitro SMA and its role in the vascular function. We found that (1) 300 microM L-NAME, a NO synthase inhibitor, and 3 microM glipizide caused a depolarization of approximately 4.5 and approximately 3.2 mV, respectively, in cells with a resting potential less negative than -60 mV; (2) NO sensor in the close vicinity of the SMA detected a NO concentration of approximately 50 nM that was suppressed by L-NAME and enhanced by L-arginine (1-1000 microM); (3) NO donor DPTA-NONOate (0.1-30 microM) applications produced about 8-245 nM of NO in the recording bath. These data indicate a NO concentration-hyperpolarization relation, with an EC50 of 22 nM. (4) Finally, L-NAME but not glipizide produced a 4.8% reduction in SMA diameter (approximately 50 microm) in the majority of SMAs, whereas NONOate (10 microM) always caused a dilation. Both the induced constriction and dilation were not significantly affected by 3 microM glipizide. We conclude that a significant amount of NO (> 50 nM) is tonically released from the in vitro SMA, which is above the EC50 for activation of K(ATP), and thus contributes to the membrane polarization. The basal release of NO also contributes to vasotone relaxation, but the K(ATP) activation appears to play little role in the relaxation of the in vitro SMA.

Animals↗

PubMed1997

Analysis of tracer transit in rat brain after carotid artery and femoral vein administrations using linear system theory.

Determination of tissue perfusion rates by MRI bolus tracking methods relies on the central volume principle which states that tissue blood flow is given by the tissue blood volume divided by the mean tracer transit time (MTT). Accurate determination of the MTT requires knowledge of the arterial input function which in MRI experiments is usually not known, especially when using small animals. The problem of unknown arterial input can be circumvented in animal experiments by directly injecting the contrast agent into a feeding artery of the tissue of interest. In the present article the passage of magnetite nanoparticles through the rat cerebral cortex is analyzed after injection into the internal carotid artery. The results are discussed in the framework of linear system theory using a one-compartment model for brain tissue and by using the well characterized gamma-variate function to describe the tissue concentration profile of the contrast agent. The results obtained from the intra-arterial tracer administration experiments are then compared with the commonly used intra-venous injection of the contrast agent in order to estimate the contribution of the peripheral circulation to the MTT values in the latter case. The experiments were analyzed using a two-compartment model and the gamma-variate function. As an application perfusion rates in normal and ischemic cerebral cortex of hypertensive rats were estimated in a model of focal cerebral ischemia. The results indicate that peripheral circulation has a significant influence on the MTT values and thus on the perfusion rates, which cannot be neglected.

Animals↗

PubMed2001

Stem cells: is there a future in plastics?

The concept that ostensibly tissue-specific stem cells can give rise to cells of heterologous lineages has gained support from studies using purified hematopoietic stem cells and sensitive donor-cell tracking methods. The ability to exploit these findings in clinical settings will probably depend on new insights into the mechanisms by which such stem cells or their progeny migrate to sites of organ damage and differentiate to cell types competent to participate in tissue regeneration.

Animals↗

PubMed2001

Fast extraction of minimal paths in 3D images and applications to virtual endoscopy.

The aim of this article is to build trajectories for virtual endoscopy inside 3D medical images, using the most automatic way. Usually the construction of this trajectory is left to the clinician who must define some points on the path manually using three orthogonal views. But for a complex structure such as the colon, those views give little information on the shape of the object of interest. The path construction in 3D images becomes a very tedious task and precise a priori knowledge of the structure is needed to determine a suitable trajectory. We propose a more automatic path tracking method to overcome those drawbacks: we are able to build a path, given only one or two end points and the 3D image as inputs. This work is based on previous work by Cohen and Kimmel [Int. J. Comp. Vis. 24 (1) (1997) 57] for extracting paths in 2D images using Fast Marching algorithm. Our original contribution is twofold. On the first hand, we present a general technical contribution which extends minimal paths to 3D images and gives new improvements of the approach that are relevant in 2D as well as in 3D to extract linear structures in images. It includes techniques to make the path extraction scheme faster and easier, by reducing the user interaction. We also develop a new method to extract a centered path in tubular structures. Synthetic and real medical images are used to illustrate each contribution. On the other hand, we show that our method can be efficiently applied to the problem of finding a centered path in tubular anatomical structures with minimum interactivity, and that this path can be used for virtual endoscopy. Results are shown in various anatomical regions (colon, brain vessels, arteries) with different 3D imaging protocols (CT, MR).

Algorithms↗

PubMed1983

Demonstration of presbycusis across repeated measures in a nonhuman primate species.

The progress of age-related hearing loss in three 31-yr-old, two 24-yr-old, and two 9-yr-old rhesus monkeys (Macaca mulatta) was repeatedly examined over a period of 3 yr. Pure-tone audiograms for seven frequencies, .125, .500, 2.000, 4.000, 16.000, 22.667, and 32.000 kHz, were obtained through the use of the psychophysical tracking method. Analysis indicated the presence of presbycusis in the older animals. Animals demonstrating presbycusis showed a progressive decrement in the ability to detect higher frequencies and an overall hearing loss at all frequencies.

Aging↗