Discrete Ladders for Parallel Transport in Transformation Groups with an Affine Connection Structure

International audienceModeling the temporal evolution of the tissues of the body is an important goal of medical image analysis, for instance for understanding the structural changes of organs affected by a pathology, or for studying the physiological growth during the life span. For such purposes we need to analyze and compare the observed anatomical differences between follow-up sequences of anatomical images of different subjects. Non-rigid registration is one of the main instruments for modeling anatomical differences from images. The aim of non-rigid registration is to encode the observed structural changes as deformation fields of the image space, which represent the warping required to match observed differences. This way, anatomical changes can be modeled and quantified by analyzing the associated deformations. The comparison of temporal evolutions thus requires the transport (or "normalization") of longitudinal deformations in a common reference frame. Normalization of longitudinal deformations can be done in different ways, depending on the feature of interest. For instance, local volume changes encoded by the scalar Jacobian determinant of longitudinal deformations can be compared by scalar resampling in a common reference frame via inter-subject registration. However, if we consider vector-valued deformation trajectories instead of scalar quantities, the transport is not uniquely defined anymore. Among the different normalization methods for deformation trajectories, the parallel transport is a powerful and promising tool which can be used within the ''diffeomorphic registration'' setting. Mathematically, parallel transporting a vector along a curve consists in translating it across the tangent spaces to the curve by preserving its parallelism according to a given derivative operation called (affine) connection. This chapter focuses on explicitly discrete algorithms for parallel transporting diffeomorphic deformations. Schild's ladder is an efficient and simple method proposed in theoretical Physics for the parallel transport of vectors along geodesics paths by iterative construction of infinitesimal geodesics parallelograms on the manifold. The base vertices of the parallelogram are given by the initial tangent vector to be transported. By iteratively building geodesic diagonals along the path, Schild's Ladder computes the missing vertex which corresponds to the transported vector. In this chapter we first show that the Schild ladder can lead to an effective computational scheme for the parallel transport of diffeomorphic deformations parameterized by tangent velocity fields. Schild's ladder may be however inefficient for transporting longitudinal deformations from image time series of multiple time points, in which the computation of the geodesic diagonals is required several times. We propose therefore a new parallel transport method based on the Schild's ladder, the "pole ladder", in which the computation of geodesics diagonals is minimized. Differently from the Schild's ladder, the pole ladder is symmetric with respect to the baseline-to-reference frame geodesic. From the theoretical point of view, we show that the pole ladder is rigorously equivalent to the Schild's ladder when transporting along geodesics. From the practical point of view, we establish the computational advantages and demonstrate the effectiveness of this very simple method by comparing with standard methods of transport on simulated images with progressing brain atrophy. Finally, we illustrate its application to a clinical problem: the measurement of the longitudinal progression in Alzheimer's disease. Results suggest that an important gain in sensitivity could be expected in group-wise comparisons

A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants

BACKGROUND: The aim of this study was to revise the 2003 Fenton Preterm Growth Chart, specifically to: a) harmonize the preterm growth chart with the new World Health Organization (WHO) Growth Standard, b) smooth the data between the preterm and WHO estimates, informed by the Preterm Multicentre Growth (PreM Growth) study while maintaining data integrity from 22 to 36 and at 50 weeks, and to c) re-scale the chart x-axis to actual age (rather than completed weeks) to support growth monitoring. METHODS: Systematic review, meta-analysis, and growth chart development. We systematically searched published and unpublished literature to find population-based preterm size at birth measurement (weight, length, and/or head circumference) references, from developed countries with: Corrected gestational ages through infant assessment and/or statistical correction; Data percentiles as low as 24 weeks gestational age or lower; Sample with greater than 500 infants less than 30 weeks. Growth curves for males and females were produced using cubic splines to 50 weeks post menstrual age. LMS parameters (skew, median, and standard deviation) were calculated. RESULTS: Six large population-based surveys of size at preterm birth representing 3,986,456 births (34,639 births < 30 weeks) from countries Germany, United States, Italy, Australia, Scotland, and Canada were combined in meta-analyses. Smooth growth chart curves were developed, while ensuring close agreement with the data between 24 and 36 weeks and at 50 weeks. CONCLUSIONS: The revised sex-specific actual-age growth charts are based on the recommended growth goal for preterm infants, the fetus, followed by the term infant. These preterm growth charts, with the disjunction between these datasets smoothing informed by the international PreM Growth study, may support an improved transition of preterm infant growth monitoring to the WHO growth charts

The long-term hospitalization experience following military service in the 1991 Gulf War among veterans remaining on active duty, 1994–2004

<p>Abstract</p> <p>Background</p> <p>Despite more than a decade of extensive, international efforts to characterize and understand the increased symptom and illness-reporting among veterans of the 1991 Gulf War, concern over possible long-term health effects related to this deployment continue. The purpose of this study was to describe the long-term hospitalization experience of the subset of U.S. Gulf War veterans still on active duty between 1994 and 2004.</p> <p>Methods</p> <p>Gulf War veterans on active duty rosters as of October 1, 1994, were identified (n = 211 642) and compared with veterans who had separated from military service and then assessed for attrition at three-year intervals during a 10-year follow-up period, examining demographic and military service characteristics, Gulf War exposure variables, and hospitalization data. Cox proportional hazard modeling was used to evaluate independent predictors of all-cause hospitalization among those still on active duty and to estimate cumulative probability of hospitalization, 1994–2004, by service branch.</p> <p>Results</p> <p>Members of our 1994 active duty cohort were more likely to be officers, somewhat older, and married compared with those who had separated from the military after serving in the 1991 Gulf War. Selected war-related exposures or experiences did not appear to influence separation with the exception of in-theater presence during the brief ground combat phase. Overall the top three diagnostic categories for hospitalizations were musculo-skeletal, injury and poisoning, and digestive disorders. Diseases of the circulatory system and symptoms, signs, and ill-defined conditions increased proportionately over time. In-theater hospitalization was the only significant independent predictor of long-term hospitalization risk among selected war-related exposures or experiences examined. The cumulative probability of hospitalization was highest for Army and lowest for Marines.</p> <p>Conclusion</p> <p>Our results were generally consistent with a previous hospitalization study of US Gulf War veterans for the period August 1991 to July 1999. Although lack of a comparison group for our study limits interpretation of overall findings, intra-cohort analyses showed no significant associations between long-term hospitalization and war-related exposures or experiences, with the exception of in-theater hospitalization, within our active duty subset of 1991 Gulf War veterans.</p

Caenorhabditis elegans Myotubularin MTM-1 Negatively Regulates the Engulfment of Apoptotic Cells

During programmed cell death, apoptotic cells are recognized and rapidly engulfed by phagocytes. Although a number of genes have been identified that promote cell corpse engulfment, it is not well understood how phagocytosis of apoptotic cells is negatively regulated. Here we have identified Caenorhabditis elegans myotubularin MTM-1 as a negative regulator of cell corpse engulfment. Myotubularins (MTMs) constitute a large, highly conserved family of lipid phosphatases. MTM gene mutations are associated with various human diseases, but the cellular functions of MTM proteins are not clearly defined. We found that inactivation of MTM-1 caused significant reduction in cell corpses in strong loss-of-function mutants of ced-1, ced-6, ced-7, and ced-2, but not in animals deficient in the ced-5, ced-12, or ced-10 genes. In contrast, overexpression of MTM-1 resulted in accumulation of cell corpses. This effect is dependent on the lipid phosphatase activity of MTM-1. We show that loss of mtm-1 function accelerates the clearance of cell corpses by promoting their internalization. Importantly, the reduction of cell corpses caused by mtm-1 RNAi not only requires the activities of CED-5, CED-12, and CED-10, but also needs the functions of the phosphatidylinositol 3-kinases (PI3Ks) VPS-34 and PIKI-1. We found that MTM-1 localizes to the plasma membrane in several known engulfing cell types and may modulate the level of phosphatidylinositol 3-phosphate (PtdIns(3)P) in vivo. We propose that MTM-1 negatively regulates cell corpse engulfment through the CED-5/CED-12/CED-10 module by dephosphorylating PtdIns(3)P on the plasma membrane

An Amphioxus Gli Gene Reveals Conservation of Midline Patterning and the Evolution of Hedgehog Signalling Diversity in Chordates

Background. Hedgehog signalling, interpreted in receiving cells by Gli transcription factors, plays a central role in the development of vertebrate and Drosphila embryos. Many aspects of the signalling pathway are conserved between these lineages, however vertebrates have diverged in at least one key aspect: they have evolved multiple Gli genes encoding functionally-distinct proteins, increasing the complexity of the hedgehog-dependent transcriptional response. Amphioxus is one of the closest living relatives of the vertebrates, having split from the vertebrate lineage prior to the widespread gene duplication prominent in early vertebrate evolution. Principal findings. We show that amphioxus has a single Gli gene, which is deployed in tissues adjacent to sources of hedgehog signalling derived from the midline and anterior endoderm. This shows the duplication and divergence of the Gli family, and hence the origin of vertebrate Gli functional diversity, was specific to the vertebrate lineage. However we also show that the single amphioxus Gli gene produces two distinct transcripts encoding different proteins. We utilise three tests of Gli function to examine the transcription regulatory capacities of these different proteins, demonstrating one has activating activity similar to Gli2, while the other acts as a weak repressor, similar to Gli3. Conclusions. These data show that the vertebrates and amphioxus have evolved functionally-similar repertoires of Gli proteins using parallel molecular routes; vertebrates via gene duplication and divergence, and amphioxus via alternate splicing of a single gene. Our results demonstrate that similar functional complexity of intercellular signalling can be achieved via different evolutionary pathways

Impact of Age on the Cerebrovascular Proteomes of Wild-Type and Tg-SwDI Mice

The structural integrity of cerebral vessels is compromised during ageing. Abnormal amyloid (Aβ) deposition in the vasculature can accelerate age-related pathologies. The cerebrovascular response associated with ageing and microvascular Aβ deposition was defined using quantitative label-free shotgun proteomic analysis. Over 650 proteins were quantified in vessel-enriched fractions from the brains of 3 and 9 month-old wild-type (WT) and Tg-SwDI mice. Sixty-five proteins were significantly increased in older WT animals and included several basement membrane proteins (nidogen-1, basement membrane-specific heparan sulfate proteoglycan core protein, laminin subunit gamma-1 precursor and collagen alpha-2(IV) chain preproprotein). Twenty-four proteins were increased and twenty-one decreased in older Tg-SwDI mice. Of these, increases in Apolipoprotein E (APOE) and high temperature requirement serine protease-1 (HTRA1) and decreases in spliceosome and RNA-binding proteins were the most prominent. Only six shared proteins were altered in both 9-month old WT and Tg-SwDI animals. The age-related proteomic response in the cerebrovasculature was distinctly different in the presence of microvascular Aβ deposition. Proteins found differentially expressed within the WT and Tg-SwDI animals give greater insight to the mechanisms behind age-related cerebrovascular dysfunction and pathologies and may provide novel therapeutic targets

A new data analysis approach for measuring longitudinal changes of metabolism in cognitively normal elderly adults

Sepideh Shokouhi,1 William R Riddle,1,&dagger; Hakmook Kang2 1Department of Radiology &amp; Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA; 2Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA &dagger;Dr William R Riddle passed away on June 8, 2016 Introduction: Previously, we discussed several critical barriers in including [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging of preclinical Alzheimer&rsquo;s disease (AD) subjects. These factors included the reference region selection and intensity normalization of PET images and the within- and across-subject variability of affected brain regions. In this study, we utilized a novel FDG-PET analysis, the regional FDG time correlation coefficient, rFTC, that can address and resolve these barriers and provide a more sensitive way of monitoring longitudinal changes in metabolism of cognitively normal elderly adults. The rFTC analysis captures the within-subject similarities between baseline and follow-up regional radiotracer distributions. Methods: The rFTC trajectories of 27 cognitively normal subjects were calculated to identify 1) trajectories of rFTC decline in individual cognitively normal subjects; 2) how these trajectories correlate with the subjects&rsquo; cognitive test scores, baseline cerebrospinal fluid (CSF) levels of amyloid beta (A&beta;), and apolipoprotein E4 (APOE-E4) status; and 3) whether similar trajectories are observed in regional/composite standardized uptake value ratio (SUVR) values. Results: While some of the subjects maintained a stable rFTC trajectory, other subjects had declining and fluctuating rFTC values. We found that the rFTC decline was significantly higher in APOE-E4 carriers compared to noncarriers (p=0.04). We also found a marginally significant association between rFTC decline and cognitive decline measured by Alzheimer&rsquo;s Disease Assessment Scale &ndash; cognitive subscale (ADAS_cog) decline (0.05). In comparison to the rFTC trajectories, the composite region of interest (ROI) SUVR trajectories did not change in any of the subjects. No individual/composite ROI SUVR changes contributed significantly to explaining changes in ADAS_cog, conversion to mild cognitive impairment (MCI), or any general changes in clinical symptoms. Conclusion: The rFTC decline may serve as a new biomarker of early metabolic changes before the MCI stage. Keywords: positron emission tomography, FDG, reference tissue normalization, regional FDG time correlation, metabolis

Modeling clustered activity increase in amyloid-beta positron emission tomographic images with statistical descriptors

Sepideh Shokouhi,1 Baxter P Rogers,1 Hakmook Kang,2 Zhaohua Ding,1 Daniel O Claassen,3 John W Mckay,1 William R Riddle1On behalf of the Alzheimer&rsquo;s Disease Neuroimaging Initiative1Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, 2Department of Biostatistics, 3Department of Neurology, Vanderbilt University, Nashville, TN, USABackground: Amyloid-beta (A&beta;) imaging with positron emission tomography (PET) holds promise for detecting the presence of A&beta; plaques in the cortical gray matter. Many image analyses focus on regional average measurements of tracer activity distribution; however, considerable additional information is available in the images. Metrics that describe the statistical properties of images, such as the two-point correlation function (S2), have found wide applications in astronomy and materials science. S2 provides a detailed characterization of spatial patterns in images typically referred to as clustering or flocculence. The objective of this study was to translate the two-point correlation method into A&beta;-PET of the human brain using 11C-Pittsburgh compound B (11C-PiB) to characterize longitudinal changes in the tracer distribution that may reflect changes in A&beta; plaque accumulation.Methods: We modified the conventional S2 metric, which is primarily used for binary images and formulated a weighted two-point correlation function (wS2) to describe nonbinary, real-valued PET images with a single statistical function. Using serial 11C-PiB scans, we calculated wS2 functions from two-dimensional PET images of different cortical regions as well as three-dimensional data from the whole brain. The area under the wS2 functions was calculated and compared with the mean/median of the standardized uptake value ratio (SUVR). For three-dimensional data, we compared the area under the wS2 curves with the subjects&rsquo; cerebrospinal fluid measures.Results: Overall, the longitudinal changes in wS2 correlated with the increase in mean SUVR but showed lower variance. The whole brain results showed a higher inverse correlation between the cerebrospinal A&beta; and wS2 than between the cerebrospinal A&beta; and SUVR mean/median. We did not observe any confounding of wS2 by region size or injected dose.Conclusion: The wS2 detects subtle changes and provides additional information about the binding characteristics of radiotracers and A&beta; accumulation that are difficult to verify with mean SUVR alone.Keywords: amyloid-beta plaques, positron emission tomography, 11C-Pittsburgh compound B, statistical descriptors, two-point correlation functio