Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction.

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome

Feasibility of identifying amyloid and hypertrophic cardiomyopathy with the use of computerized quantitative texture analysis of clinical echocardiographic data

AbstractUltrasound tissue characterization, the evaluation of certain physical properties of a tissue based on its acoustic properties, is an evolving application in echocardiography. The ability to identify acutely and chronically injured tissue has been demonstrated in a number of animal studies, but data in humans are limited. The present study tested the hypothesis that quantitative echocardiographic texture analysis, a method of evaluating the spatial pattern of echoes in echocardiographic images, would differentiate amyloid and hypertrophic cardiomyopathy from normal myocardium. Routine clinical echocardiographic data were obtained on 34 subjects at the Mayo Clinic (10 normal subjects, 10 patients with amyloid heart disease, 8 patients with hypertrophic cardiomyopathy and 6 patients with left ventricular hypertrophy due to hypertension). Standard videotape recordings of these echocardiograms were analyzed at the University of Iowa.Echocardiographic data were digitized with use of a calibrated, 256 gray level digitization system. Quantitative texture analysis was performed on data from the ventricular septum and posterior left ventricular wall in end-diastolic and end-systolic, short-axis and long-axis echocardiographic images. The gray level run length texture variables were able to discriminate hypertrophic cardiomyopathy and amyloid heart disease from normal myocardium and from each other (p < 0.0083 for comparisons of the quantitative texture features of amyloid versus hypertrophic cardiomyopathy versus normal by multivariate analysis of variance). The texture of the myocardium in hypertensive left ventricular hypertrophy not associated with amyloid or hypertrophic cardiomyopathy was in general not significantly different from that of normal myocardium.On the basis of these data, it was concluded that quantitative texture analysis of clinical echocardiographic data has the potential to identify amyloid and hypertrophic cardiomyopathy; false positive results occur rarely in left ventricular hypertrophy due to hypertension. Further prospective studies of this technique are needed to establish its utility in identifying the etiology of clinical cardiomyopathies

Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction☆

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome

Reduction in Overall Occurrences of Ischemic Events with Vorapaxar: Results from TRACER

BACKGROUND: Clinical trials traditionally use time-to-first-event analysis embedded within the composite endpoint of cardiovascular death (CVD), myocardial infarction (MI), or stroke. However, many patients have \u3e1 event, and this approach may not reflect overall experience. We addressed this by analyzing all cardiovascular events in TRACER. METHODS AND RESULTS: TRACER randomized 12 944 patients with non-ST-segment elevation acute coronary syndromes to placebo or to protease-activated receptor 1 antagonist vorapaxar with a median follow-up of 502 days (interquartile range, 349 to 667). Analysis of vorapaxar\u27s effect on recurrent CVD, MI, or stroke was prespecified using the Wei, Lin, and Weissfeld approach. Vorapaxar did not reduce the first occurrence of the primary endpoint of CVD, MI, stroke, revascularization, or rehospitalization for recurrent ischemia, but reduced the secondary composite endpoint of CVD, MI, or stroke (14.7% vorapaxar vs. 16.4% placebo; hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.02; number needed to treat [NNT], 81). Recurrent secondary events occurred in 2.7% of patients. Vorapaxar reduced overall occurrences of ischemic events, first and subsequent (HR, 0.88; 95% CI, 0.80 to 0.98; P=0.02; NNT, 51). Also, there was a trend indicating that vorapaxar reduced the expanded endpoint, including revascularization and rehospitalization for recurrent ischemia (HR, 0.92; 95% CI, 0.84 to 1.01; P=0.09). Vorapaxar increased overall occurrences of moderate and severe Global Use of Strategies to Open Occluded Coronary Arteries bleeding (HR, 1.42; 95% CI, 1.21 to 1.66; PP\u3c0.001). CONCLUSIONS: Vorapaxar reduced overall occurrences of ischemic events, but increased bleeding. These exploratory findings broaden our understanding of vorapaxar\u27s potential and expand our understanding of the value of capturing recurrent events

Tolerability and Efficacy of a Pediatric Granule Formulation of Artesunate-Mefloquine in Young Children from Cameroon with Uncomplicated Falciparum Malaria

A fixed-dose pediatric formulation of artesunate and mefloquine (Artequin Pediatric) has been developed. In this open, non-comparative study in Cameroonian children with uncomplicated falciparum malaria, the safety and efficacy of this formulation was tested, with a particular emphasis on the risk of neuropsychiatric adverse events (AEs). In total, 220 subjects, weighing between 10 and 20 kg, were enrolled; 213 qualified for analysis. Artesunate-mefloquine was given once daily for 3 days. Overall, 13.1% of patients reported mild to moderate neuropsychiatric AEs (elicited through a structured questionnaire or reported spontaneously) out of which 3.8% (mainly insomnia) were considered drug-related. Other drug-related AEs were infrequent (< 3%). Polymerase chain reaction-corrected cure rate (adequate clinical and parasitological response) determined by survival analysis at 28 and 63 days was 96.6%. New infections were observed in 11.2% of evaluable patients at 63 days. The new formulation was well tolerated and efficacious in the population investigated

Computerized assessment of vessel morphological changes during treatment of glioblastoma multiforme: Report of a case imaged serially by MRA over four years

A patient with glioblastoma mutliforme underwent serial computerized analysis of tumor-associated vasculature defined from magnetic resonance angiographic (MRA) scans obtained over almost a four year period. The clinical course included tumor resection with subsequent radiation therapy, a long symptom-free interval, emergence of a new malignant focus, resection of that focus, a stroke, and treatment with chemotherapy and anti-angiogenic therapy. Image analysis methods included segmentation of vessels from each MRA and statistical comparison of vessel morphology over 4 regions of interest (the initial tumor site, the second tumor site, a distant control region, and the entire brain) to the same 4 regions of interest in 50 healthy volunteers (26 females and 24 males; mean age 39 years). Results suggested that following completion of focal radiation therapy (RT) vessel shape abnormalities, if elevated at the time of RT completion, may progressively normalize for months in focal regions, that progressively severe vessel shape abnormalities can precede the emergence of a gadolinium enhancing lesion by months, that lesion resection can produce a dramatic but highly transient drop in abnormal vessel tortuosity both focally and globally, and that treatment with anti-angiogenic agents does not necessarily normalize vessel shape. Quantitative measurements of vessel morphology as defined from MRA may provide useful insights into tumor development and response to therapy

On the origin and magnitude of surface stresses due to metal nanofilms

Metallisation is a vital process for micro- and nanofabrication, allowing the controlled preparation of material surfaces with thin films of a variety of metals. The films are often subjected to further processing, including etching, patterning, chemical modification, and additional lamination. The extensive applications of metallised substrates include chemical sensors and nanoelectronics. Here, we report an experimental study of the metallization of silicon cantilevers with nano-films of chromium and titanium. Analysis of the stress distribution throughout the cantilever showed that metallisation causes a constant stress along the length of the beam, which can be calculated from interferometric quantification of the beam curvature. The structure of the metal/silicon interface was imaged using electron microscopy in an attempt to ascertain the physical origin of the stress. A theoretical model is constructed for the stressed beam system, and it is shown that there is no single parameter that can describe the change in stress. The resultant structure after deposition varies significantly for each metal, which gives rise to a variety of stress directions and magnitudes

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo