Spatiotemporal alignment of in utero BOLD-MRI series

Purpose: To present a method for spatiotemporal alignment of in-utero magnetic resonance imaging (MRI) time series acquired during maternal hyperoxia for enabling improved quantitative tracking of blood oxygen level-dependent (BOLD) signal changes that characterize oxygen transport through the placenta to fetal organs. Materials and Methods: The proposed pipeline for spatiotemporal alignment of images acquired with a single-shot gradient echo echo-planar imaging includes 1) signal nonuniformity correction, 2) intravolume motion correction based on nonrigid registration, 3) correction of motion and nonrigid deformations across volumes, and 4) detection of the outlier volumes to be discarded from subsequent analysis. BOLD MRI time series collected from 10 pregnant women during 3T scans were analyzed using this pipeline. To assess pipeline performance, signal fluctuations between consecutive timepoints were examined. In addition, volume overlap and distance between manual region of interest (ROI) delineations in a subset of frames and the delineations obtained through propagation of the ROIs from the reference frame were used to quantify alignment accuracy. A previously demonstrated rigid registration approach was used for comparison. Results: The proposed pipeline improved anatomical alignment of placenta and fetal organs over the state-of-the-art rigid motion correction methods. In particular, unexpected temporal signal fluctuations during the first normoxia period were significantly decreased (P < 0.01) and volume overlap and distance between region boundaries measures were significantly improved (P < 0.01). Conclusion: The proposed approach to align MRI time series enables more accurate quantitative studies of placental function by improving spatiotemporal alignment across placenta and fetal organs.National Institutes of Health (NIH) . Grant Numbers: U01 HD087211 , R01 EB017337 Consejeria de Educacion, Juventud y Deporte de la Comunidad de Madrid (Spain) through the Madrid-MIT M+Vision Consortium

Temporal Registration in In-Utero Volumetric MRI Time Series

We present a robust method to correct for motion and deformations in in-utero volumetric MRI time series. Spatio-temporal analysis of dynamic MRI requires robust alignment across time in the presence of substantial and unpredictable motion. We make a Markov assumption on the nature of deformations to take advantage of the temporal structure in the image data. Forward message passing in the corresponding hidden Markov model (HMM) yields an estimation algorithm that only has to account for relatively small motion between consecutive frames. We demonstrate the utility of the temporal model by showing that its use improves the accuracy of the segmentation propagation through temporal registration. Our results suggest that the proposed model captures accurately the temporal dynamics of deformations in in-utero MRI time series.National Institutes of Health (U.S.) (NIH NIBIB NAC P41EB015902)National Institutes of Health (U.S.) (NIH NICHD U01HD087211)National Institutes of Health (U.S.) (NIH NIBIB R01EB017337)Wistron CorporationMerrill Lynch Wealth Management (Fellowship

Temporal Registration in In-Utero Volumetric MRI Time Series

We present a robust method to correct for motion and deformations in in-utero volumetric MRI time series. Spatio-temporal analysis of dynamic MRI requires robust alignment across time in the presence of substantial and unpredictable motion. We make a Markov assumption on the nature of deformations to take advantage of the temporal structure in the image data. Forward message passing in the corresponding hidden Markov model (HMM) yields an estimation algorithm that only has to account for relatively small motion between consecutive frames. We demonstrate the utility of the temporal model by showing that its use improves the accuracy of the segmentation propagation through temporal registration. Our results suggest that the proposed model captures accurately the temporal dynamics of deformations in in-utero MRI time series.National Institutes of Health (U.S.) (NIH NIBIB NAC P41EB015902)National Institutes of Health (U.S.) (NIH NICHD U01HD087211)National Institutes of Health (U.S.) (NIH NIBIB R01EB017337)Wistron CorporationMerrill Lynch Wealth Management (Fellowship

Molecular and Cellular Mechanisms of Preeclampsia

This Special Issue on the “Molecular and Cellular Mechanisms of Preeclampsia” belongs to the section “Molecular Pathology, Diagnostics, and Therapeutics” of the International Journal of Molecular Sciences. It was a very successful Special Issue as it contains 20 published papers, including one editorial, nine original research papers, and ten reviews on the topic. The original publications cover a wide spectrum of topics, including alterations and involvement of specific factors during preeclampsia, new non-invasive technologies to identify changes, new treatment options, animal models, gender aspects, and effects of the pregnancy pathology later in life. The review publications again cover a wide spectrum of topics, including factors and pathways involved in preeclampsia, effects on the maternal vascular and immune systems, effects on the placenta and the trophoblast, epigenetic changes, new preventive strategies, and new views on the current hypotheses on preeclampsia. Taken together, this Special Issue gives a fantastic overview on a broad spectrum of topics, all of which are important to identify the real etiology of preeclampsia and to finally develop real treatment options

Development of optical instrumentation and methods to monitor brain oxygen metabolism: application to neonatal brain injury

Hypoxic ischemic encephalopathy (HIE) is a relatively common and potentially devastating form of perinatal brain injury, associated with neurodevelopmental problems and mortality. HIE is an evolving process. There is a need for real-time, in-vivo measurements of brain oxygenation and metabolism for clinical assessment in the first days of life, to detect those at risk of further brain injury who may benefit from redirection of care. This thesis describes the development of a broadband near-infrared spectroscopy (NIRS) system to monitor changes in metabolism and haemodynamics in HIE infants at the cotside. This system uses multiple wavelengths (λ=136,770-905nm) to monitor changes in concentration of the oxidation state of cytochrome-c-oxidase (oxCCO) as well as haemoglobin oxygenation. Changes in oxCCO are indicative of CCO redox state changes within mitochondria and therefore represent oxygen utilization. The 2-channel system incorporates a broadband source, optical fibres, spectrograph and CCD. This set up is flexible and robustly monitors changes in haemoglobin and oxCCO. The system was developed specifically for the neonatal intensive care unit (NICU) and has been demonstrated on 38 brain-injured newborn infants (28 with HIE). Data was continuously collected over the frontal lobe simultaneously with systemic data for multimodal analysis. This allows the study of cerebral changes in response to global pathophysiological events. HIE was assessed by magnetic resonance spectroscopy measurement of lactate to NAA ratio (Lac/NAA), the gold standard for neurodevelopmental outcome. Initially the analysis focussed on spontaneous hypoxias. The relationship between haemoglobin oxygenation and oxCCO during hypoxic events was significantly associated with Lac/NAA (n=22,r=0.51,p=0.02). Further investigation of the dynamics of the cerebral changes during hypoxias found oxCCO differences with injury severity (not observed in haemoglobins). Finally, the relationship between cerebral signals and systemic physiology was investigated with a multivariate statistical technique. A strong relationship between oxCCO and systemic changes indicated severe brain injury (n=12,p=0.04)

Antioxidant and DPPH-Scavenging Activities of Compounds and Ethanolic Extract of the Leaf and Twigs of Caesalpinia bonduc L. Roxb.

Antioxidant effects of ethanolic extract of Caesalpinia bonduc and its isolated bioactive compounds were evaluated in vitro. The compounds included two new cassanediterpenes, 1α,7α-diacetoxy-5α,6β-dihydroxyl-cass-14(15)-epoxy-16,12-olide (1)and 12α-ethoxyl-1α,14β-diacetoxy-2α,5α-dihydroxyl cass-13(15)-en-16,12-olide(2); and others, bonducellin (3), 7,4’-dihydroxy-3,11-dehydrohomoisoflavanone (4), daucosterol (5), luteolin (6), quercetin-3-methyl ether (7) and kaempferol-3-O-α-L-rhamnopyranosyl-(1Ç2)-β-D-xylopyranoside (8). The antioxidant properties of the extract and compounds were assessed by the measurement of the total phenolic content, ascorbic acid content, total antioxidant capacity and 1-1-diphenyl-2-picryl hydrazyl (DPPH) and hydrogen peroxide radicals scavenging activities.Compounds 3, 6, 7 and ethanolic extract had DPPH scavenging activities with IC50 values of 186, 75, 17 and 102 μg/ml respectively when compared to vitamin C with 15 μg/ml. On the other hand, no significant results were obtained for hydrogen peroxide radical. In addition, compound 7 has the highest phenolic content of 0.81±0.01 mg/ml of gallic acid equivalent while compound 8 showed the highest total antioxidant capacity with 254.31±3.54 and 199.82±2.78 μg/ml gallic and ascorbic acid equivalent respectively. Compound 4 and ethanolic extract showed a high ascorbic acid content of 2.26±0.01 and 6.78±0.03 mg/ml respectively.The results obtained showed the antioxidant activity of the ethanolic extract of C. bonduc and deduced that this activity was mediated by its isolated bioactive compounds

Drug Discovery

Natural products are a constant source of potentially active compounds for the treatment of various disorders. The Middle East and tropical regions are believed to have the richest supplies of natural products in the world. Plant derived secondary metabolites have been used by humans to treat acute infections, health disorders and chronic illness for tens of thousands of years. Only during the last 100 years have natural products been largely replaced by synthetic drugs. Estimates of 200 000 natural products in plant species have been revised upward as mass spectrometry techniques have developed. For developing countries the identification and use of endogenous medicinal plants as cures against cancers has become attractive. Books on drug discovery will play vital role in the new era of disease treatment using natural products