Publications by Year: 2013

In this paper, we propose a stochastic model of photoplethysmographic signals that is able to synthesize an arbitrary number of other statistically equivalent signals to the one under analysis. To that end, we first preprocess the pulse signal to normalize and time-align pulses. In a second stage, we design a single-pulse model, which consists of ten parameters. In the third stage, the time evolution of this ten-parameter vector is approximated by means of two autoregressive moving average models, one for the trend and one for the residue; this model is applied after a decorrelation step which let us to process each vector component in parallel. The experiments carried out show that the model we here propose is able to maintain the main features of the original signal; this is accomplished by means of both a linear spectral analysis and also by comparing two measures obtained from a nonlinear analysis. Finally, we explore the capability of the model to: 1) track physical activity; 2) obtain statistics of clinical parameters by model sampling; and 3) recover corrupted or missing signal epochs by synthesis.

The purpose of this study was to quantify and model various types of cell death for a small-cell lung cancer (SCLC) cell line (U1690) after exposure to a 137Cs source and as well as to compare the linear-quadratic (LQ) and repairable-conditionally repairable model (RCR). This study is based on four different experiments that were taken place at Cancer Centrum Karolinska (CCK). A human small-cell lung cancer (SCLC) cell line after the exposure to a 137Cs source was used for the extraction of the clonogenic cell survival curve. Additionally, for the determination and quantification of various modes of cell death the method of fluorescence staining was implemented, where the cell deaths were categorized based on morphological characteristics. The percentage of cells in each phase of the cell cycle was investigated with flow cytometry analysis. The quantification of senescent cells was performed by staining the samples with senescence-associated β-galactosidase (SA-β-Gal) solution and then scoring as senescent cells those that had incorporated the substance. These data were introduced into a maximum likelihood fitting to calculate the best estimates of the parameters used by the examined model. In this model, the modes of cell death are divided into three categories: apoptotic, senescent and other types of cell death (necrotic/apoptotic, necrotic, micronuclei and giant). In the clonogenic cell survival assay, the fitting of the RCR model gives a χ(2)-value of 6.10 whereas for the LQ model became 9.61. In the fluorescence microscopy and senescence assay, the probability of the three different modes of cell death on day 2 seems to increases with a dose up to about 10 Gy where there is saturation. On day 7 a significant induction of apoptosis in a dose- and time-dependent manner was evident, whereas senescence was slightly increased in response to dose but not to time. As for the ’other types of cell death’ mode on day 7 showed a higher probability than the one on day 2 and as well as a prominent dose-dependence. The RCR model fits better to the experimental data than the LQ model. On day 2 there is a slight increase of the apoptotic and senescent probability with dose. On the other hand, on day 7 the shape of the curve of apoptosis differs and a sigmoidal increase with dose is observed. At both time-points, the present model fits the data reasonably well. Due to the fact that the clonogenic survival does not coincide with the one extracted from the fluorescence microscopy, a more accurate way to quantify cell death needs to be used, e.g. computerized video time-lapse (CVTL).

Knowledge of microstructural features of nerve fascicles, such as their axon diameter, is crucial for understanding normal function in the central and peripheral nervous systems as well as assessing changes due to pathologies. In this study double-pulsed field gradient (d-PFG) filtered MRI was used to map the average axon diameter (AAD) in porcine spinal cord, which was then compared to AADs measured with optical microscopy of the same specimen, as a way to further validate this new MRI method. A novel 3D d-PFG acquisition scheme was used to obtain AADs in each voxel of a coronal slice of rat brain corpus callosum. AAD measurements were also acquired using optical microscopy performed on histological sections and validated using a glass capillary array phantom.

Spectral editing with CP and INEPT in (13)C MAS NMR enables identification of rigid and mobile molecular segments in concentrated assemblies of surfactants, lipids, and/or proteins. In order to get stricter definitions of the terms "rigid" and "mobile", as well as resolving some ambiguities in the interpretation of CP and INEPT data, we have developed a theoretical model for calculating the CP and INEPT intensities as a function of rotational correlation time τc and C-H bond order parameter SCH, taking the effects of MAS into account. According to the model, the range of τc can at typical experimental settings (5kHz MAS, 1ms ramped CP at 80-100kHz B1 fields) be divided into four regimes: fast (τc0.1ms). In the fast regime, the CP and INEPT intensities are independent of τc, but strongly dependent on |SCH|, with a cross-over from dominating INEPT to dominating CP at |SCH|>0.1. In the intermediate regime, neither CP nor INEPT yield signal on account of fast T1ρ and T2 relaxation. In both the fast-intermediate and slow regimes, there is exclusively CP signal. The theoretical predictions are tested by experiments on the glass-forming surfactant n-octyl-β-d-maltoside, for which τc can be varied continuously in the nano- to millisecond range by changing the temperature and the hydration level. The atomistic details of the surfactant dynamics are investigated with MD simulations. Based on the theoretical model, we propose a procedure for calculating CP and INEPT intensities directly from MD simulation trajectories. While MD shows that there is a continuous gradient of τc from the surfactant polar headgroup towards the methyl group at the end of the hydrocarbon chain, analysis of the experimental CP and INEPT data indicates that this gradient gets steeper with decreasing temperature and hydration level, eventually spanning four orders of magnitude at completely dry conditions.

Despite recognition that nearly one-third of the 6300 amphibian species are threatened with extinction, our understanding of the general ecology and population status of many amphibians is relatively poor. A widely-used method for monitoring amphibians involves injecting captured individuals with unique combinations of colored visible implant elastomer (VIE). We compared VIE identification to a less-invasive method - computer-assisted photographic identification (photoID) - in endangered Jollyville Plateau salamanders (Eurycea tonkawae), a species with a known range limited to eight stream drainages in central Texas. We based photoID on the unique pigmentation patterns on the dorsal head region of 1215 individual salamanders using identification software Wild-ID. We compared the performance of photoID methods to VIEs using both ’high-quality’ and ’low-quality’ images, which were taken using two different camera types and technologies. For high-quality images, the photoID method had a false rejection rate of 0.76% compared to 1.90% for VIEs. Using a comparable dataset of lower-quality images, the false rejection rate was much higher (15.9%). Photo matching scores were negatively correlated with time between captures, suggesting that evolving natural marks could increase misidentification rates in longer term capture-recapture studies. Our study demonstrates the utility of large-scale capture-recapture using photo identification methods for Eurycea and other species with stable natural marks that can be reliably photographed.

There is increasing evidence regarding the importance of the hypothalamus for understanding sex differences in relation to neurological, psychiatric, endocrine and sleep disorders. Although different in histology, physiology, connections and function, multiple hypothalamic nuclei subserve non-voluntary functions and are nodal points for the purpose of maintaining homeostasis of the organism. Thus, given the critical importance of hypothalamic nuclei and their key multiple roles in regulating basic functions, it is important to develop the ability to conduct in vivo human studies of anatomic structure, volume, connectivity, and function of hypothalamic regions represented at the level of its nuclei. The goals of the present study were to develop a novel method of semi-automated volumetric parcellation for the human hypothalamus that could be used to investigate clinical conditions using MRI and to demonstrate its applicability. The proposed new method subdivides the hypothalamus into five parcels based on visible anatomic landmarks associated with specific nuclear groupings and was confirmed using two ex vivo hypothalami that were imaged in a 7 T (7 T) scanner and processed histologically. Imaging results were compared with histology from the same brain. Further, the method was applied to 44 healthy adults (26 men; 18 women, comparable on age, handedness, ethnicity, SES) to derive normative volumes and assess sex differences in hypothalamic regions using 1.5 T MRI. Men compared to women had a significantly larger total hypothalamus, relative to cerebrum size, similar for both hemispheres, a difference that was primarily driven by the tuberal region, with the sex effect size being largest in the superior tuberal region and, to a lesser extent, inferior tuberal region. Given the critical role of hypothalamic nuclei in multiple chronic diseases and the importance of sex differences, we argue that the use of the novel methodology presented here will allow for critical investigations of these disorders and further delineation of potential treatments, particularly sex-specific approaches to gene and drug discoveries that involve hypothalamic nuclei.

BACKGROUND: Whether African Americans (AA) are more susceptible to COPD than non-Hispanic Whites (NHW) and whether racial differences in disease phenotype exist is controversial. The objective is to determine racial differences in the extent of emphysema and airway remodeling in COPD. METHODS: First, 2,500 subjects enrolled in the COPDGene study were used to evaluate racial differences in quantitative CT (QCT) parameters of% emphysema, air trapping and airway wall thickness. Independent variables studied included race, age, gender, education, BMI, pack-years, smoking status, age at smoking initiation, asthma, previous work in dusty job, CT scanner and center of recruitment.

Biophysical models that describe the outcome of white matter diffusion MRI experiments have various degrees of complexity. While the simplest models assume equal-sized and parallel axons, more elaborate ones may include distributions of axon diameters and axonal orientation dispersions. These microstructural features can be inferred from diffusion-weighted signal attenuation curves by solving an inverse problem, validated in several Monte Carlo simulation studies. Model development has been paralleled by microscopy studies of the microstructure of excised and fixed nerves, confirming that axon diameter estimates from diffusion measurements agree with those from microscopy. However, results obtained in vivo are less conclusive. For example, the amount of slowly diffusing water is lower than expected, and the diffusion-encoded signal is apparently insensitive to diffusion time variations, contrary to what may be expected. Recent understandings of the resolution limit in diffusion MRI, the rate of water exchange, and the presence of microscopic axonal undulation and axonal orientation dispersions may, however, explain such apparent contradictions. Knowledge of the effects of biophysical mechanisms on water diffusion in tissue can be used to predict the outcome of diffusion tensor imaging (DTI) and of diffusion kurtosis imaging (DKI) studies. Alterations of DTI or DKI parameters found in studies of pathologies such as ischemic stroke can thus be compared with those predicted by modelling. Observations in agreement with the predictions strengthen the credibility of biophysical models; those in disagreement could provide clues of how to improve them. DKI is particularly suited for this purpose; it is performed using higher b-values than DTI, and thus carries more information about the tissue microstructure. The purpose of this review is to provide an update on the current understanding of how various properties of the tissue microstructure and the rate of water exchange between microenvironments are reflected in diffusion MRI measurements. We focus on the use of biophysical models for extracting tissue-specific parameters from data obtained with single PGSE sequences on clinical MRI scanners, but results obtained with animal MRI scanners are also considered. While modelling of white matter is the central theme, experiments on model systems that highlight important aspects of the biophysical models are also reviewed.

Based on high-resolution diffusion tensor magnetic resonance imaging (DTI) tractographic analyses in 39 healthy adult subjects, we derived patterns of connections and measures of volume and biophysical parameters, such as fractional anisotropy (FA) for the human middle longitudinal fascicle (MdLF). Compared to previous studies, we found that the cortical connections of the MdLF in humans appear to go beyond the superior temporal (STG) and angular (AG) gyri, extending to the temporal pole (TP), superior parietal lobule (SPL), supramarginal gyrus, precuneus and the occipital lobe (including the cuneus and lateral occipital areas). Importantly, the MdLF showed a striking lateralized pattern with predominant connections between the TP, STG and AG on the left and TP, STG and SPL on the right hemisphere. In light of the results of the present study, and of the known functional role of the cortical areas interconnected by the MdLF, we suggested that this fiber pathway might be related to language, high order auditory association, visuospatial and attention functions.

We hypothesized that atomoxetine (ATMX) would produce similar brain effects in attention-deficit/hyperactivity disorder (ADHD) as those of methylphenidate (MPH). Eleven ADHD adults performed the Multi-Source Interference Task (MSIT) during functional magnetic resonance imaging (fMRI) at baseline and after 6 weeks of ATMX treatment. ATMX was associated with increased fMRI activation of dorsolateral prefrontal cortex, parietal cortex and cerebellum but not dorsal anterior midcingulate cortex (daMCC). These results suggest that ATMX and MPH have similar but not identical brain effects.