Magnetic resonance imaging of migrating neuronal precursors in normal and hypoxic-ischemic neonatal rat brains by intraventricular MPIO labeling

Proceedings of the IEEE Engineering in Medicine and Biology Society Conference, 2008, p. 363-366In this study, 10-day-old normal rats (n=6) and hypoxic-ischemic (H-I) neonatal rats (n=6) were injected with the micronsized iron oxide particles (MPIOs) into the anterior lateral ventricle. 2D and 3D high-spatial resolution MRI were performed with a 7T animal scanner 1 day before the MPIOs injection and hour 3, day 3, day 7 and day 14 after the MPIOs injection. Intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU) were used to label newly produced cells, and were given thrice daily for 2 days before sacrifice. Immunohistochemistry and Prussian blue staining indicated that iron particles were inside the nestin+ and BrdU+ neural progenitor cells (NPCs), glial-fibrillary-acidic-protein-positive (GFAP+) astrocytes-like progenitor cells, and neuronal-nuclei-positive (NeuN+) mature neurons. Here we demonstrate that, in normal neonatal rat brain, the migrating pathway of the endogenous NPCs with MPIO is mainly along the rostral migratory stream to the olfactory bulb. In H-I neonatal rat brain, the migration of endogenous NPCs with MPIO is mainly towards the ischemic regions. Therefore, in vivo magnetic cell labeling of endogenous NPCs with MPIO and subsequently non-invasive, serial MRI monitoring should open up a new approach to probe into the mechanism of cell migration in the developmental brain under physiological and pathologic conditions. © 2008 IEEE.published_or_final_versio

MRI detection of progenitor cell migrations during postnatal rat brain development by in situ MPIO labeling

Molecules & Cells: Novel Applications - Poster presentationIn this study, micron-sized iron oxide particles (MPIOs) were injected into the left anterior lateral ventricle of 10-day-old normal rats. T2- and T2*-weighted images were acquired using a 7T scanner at day 1, 3, 7 and 14 after the MPIO injection. Histological analyses were then performed to identify MPIOs in different migrating cells, namely, neural progenitor and astrocytes-like progenitor cells. The migrating pathways of the MPIO-labeled endogenous progenitors exhibited a predominantly bidirectional, rostrocaudal pattern in tangential orientation. Such in situ MPIO labeling approach opens the possibility of using MRI to study the mechanism of cell migration in developing brain.published_or_final_versionThe 17th Scientific Meeting & Exhibition of the International Society of Magnetic Resonance in Medicine (ISMRM), Honolulu, HI., 18-24 April 2009. In Proceedings of ISMRM 17th Scientific Meeting & Exhibition, 2009, p. 316

Assessment of iron deposition and white matter maturation in infant brains by using enhanced T2 start weighted angiography (ESWAN): R2* versus phase values

published_or_final_versio

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Evolution of MR DTI changes in neonatal rats after mild hypoxic-ischemic insult

7-day-old mild hypoxic-ischemic (H-I) rats (n=12) were studied at 7T with diffusion tensor imaging (DTIs) in day 1, 3 and 7 post H-I insult. The apparent diffusion coefficient (ADC), fractional anisotropy (FA) and directional diffusivities (¦Ë// and ¦Ë¡Í) values were measured in white matter (WM) and gray matter (GM) lesion and their contralateral side. In day 1, the ADC, FA and ¦Ë// values showed significant decrease in GM lesion whilst WM lesion only showed a significant ADC increase. In day 3, the significant FA decrease and ¦Ë¡Í increase were found in GM lesion. Significant ADC and ¦Ë¡Í increase, and FA decrease were observed in the ipsilateral WM. By day 7, all DTI values were not statistically different between two hemispheres. Thus DTI is a sensitive method to study the early transient GM and WM changes after mild H-I insult by probing the microstructural changes

MRI detection of the migrating neuronal precursors in normal and hypoxic-ischemic neonatal rat brain by in vivo cell label with MPIO

In this study,10-day-old normal rats (n=6) and hypoxic-ischemic (H-I) neonatal rats (n=6) were injected with the micronsized iron oxide particles (MPIOs) into the anterior lateral ventricle. 2D and 3D gradient echo MRI was performed with a 7T animal scanner in hour 3, day 3, day 7 and day 14 after the MPIOs injection. Then animals were sacrificed for double staining with iron and mature neurons. In normal neonatal rat brain, the migrating pathway of the endogenous neural progenitor cells (NPCs) with MPIO is mainly along the rostral migratory stream to the olfactory bulb. In H-I neonatal rat brain, the migration of endogenous NPCs with MPIO is mainly toward injured boundary. MRI can facilely detect the above migrations in 2 weeks. Therefore, in vivo magnetic cell labeling of endogenous NPCs with MPIO and subsequently non-invasive, serial MRI monitoring should open up a new approach to probe into the mechanism of cell migration in the developmental brain under physiological and pathologic states

A free-breathing non-contrast-enhanced pulmonary magnetic resonance angiography at 3 Tesla

Background: The breathhold contrast-enhanced three-dimensional magnetic resonance angiography (MRA) using T1-weighted gradient-echo imaging sequence is the standard technique for MRA of the thorax. However, this technique is not desirable for certain patients with respiratory insufficiency, serious renal impairment, or allergy to contrast agents. The objective of this study was to optimize and evaluate a non-contrast-enhanced free-breathing pulmonary MRA protocol at 3 Tesla. Methods: The time-of-flight protocol was based on a two-dimensional T1-weighted turbo field echo sequence with slice-selective inversion recovery and magnetization transfer preparation together with respiratory navigator gating, cardiac gating, and parallel imaging. Optimal values for time of inversion delay, flip angle and slice thickness were experimentally determined and used for all subjects. Results: Excellent pulmonary MRA images, in which the 7th order branches of pulmonary arteries could be reliably identified, were obtained in the 12 free-breathing healthy volunteers. TI of ∼300 ms provides the best suppression of background thoracic and cardiac muscles and effective inflow enhancement. With increasing flip angle, the pulmonary vessels gradually brightened and exhibited optimal contrast at 20°-30°. The 2 mm slice thickness and 0.5 mm slice overlap is suitable for visualization of the peripheral pulmonary vessel. Conclusions: The MRA protocol at 3 Tesla may have clinical significance for pulmonary vascular imaging in patients who are not available for contrast-enhanced 3D MRA and CT angiography examination or are unable to sustain a long breath-hold.link_to_OA_fulltex

MR imaging assessment of lumbar intervertebral disk degeneration and age-related changes: apparent diffusion coefficient versus T2 quantitation

BACKGROUND AND PURPOSE: T2 and ADC mappings are 2 quantitative MR imaging tools for assessing IVDD. This study aimed to compare these 2 measures in detecting IVDD and its age-related changes. MATERIALS AND METHODS: Thirty-seven asymptomatic volunteers and 28 patients with back pain or sciatica were examined, and their lumbar disk T2 and ADC maps were quantified via sagittal imaging protocols at 1.5T. For all participants, the Pfirrmann system was used by 2 radiologists for grading disks. T2 and ADC values in the inner portion of disks were measured, and their variances in different grades were analyzed by 1-way ANOVA testing. The ability of T2 and ADC measures to differentiate IVDD grades was compared on the basis of their ROC curves. For asymptomatic subjects, the correlations between age and the 2 MR imaging measures were assessed by the Pearson correlation test. RESULTS: Both T2 and ADC values were found to decrease with the increasing Pfirrmann grades except T2 in grade V. Significant T2 differences were seen among grades I-IV, but not between grades IV and V. There were no significant ADC differences among grades I-III. Moreover, the areas under the ROC curves differed significantly (0.95 and 0.67 for T2 and ADC, respectively). Linear regression analysis revealed that T2 yielded more significant correlation with age (r = -0.77) than ADC did (r = -0.37). CONCLUSIONS: T2 quantitation provides a more sensitive and robust approach for detecting and characterizing the early stage of IVDD and age-related disk changes.link_to_OA_fulltex

A note on solving real linear systems with the complex schur decompositon

When using the complex Schur decomposition to solve a real linear system, the computed solution generally has a complex component due to roundoff error. It has recently been shown by Moravitz Martin and Van Loan [SIAM J. Matrix Anal., 29 (2007), pp. 177-183.] that the real part of the computed solution solves a nearby real linear system. In this note the properties of sum (and the difference) of the real part and the image part of the computed approximation is examined, we further show that they can be the exact solution of a nearby real linear system, respectively

In vivo MRI of endogenous stem/progenitor cell migration from subventricular zone in normal and injured developing brains

Understanding the alterations of migratory activities of the endogenous neural stem/progenitor cells (NSPs) in injured developing brains is becoming increasingly imperative for curative reasons. In this study, 10-day-old neonatal rats with and without hypoxic-ischemic (HI) insult at postnatal day 7 were injected intraventricularly with micron-sized iron oxide particles (MPIOs), followed by serial high-resolution MRI at 7 T for 2 weeks. MRI findings were correlated to the histological analysis using iron staining and several immunohistochemical double staining. The results indicated that in normal and HI-injured brains the NSPs from the subventricular zone (SVZ) were labeled by MPIOs, and migrated as newly created cells (iron+/BrdU+), neuroblasts (iron+/nestin+), astrocytes or astrocytes-like progenitor cells (iron+/GFAP+), and mature neurons (iron+/NeuN+). In normal brains, the endogenous NSPs mainly exhibited a tangential pattern in both rostral and caudal directions. The NSP radial migratory pattern could be observed in some rats. In the HI-injured brains during the same developmental period, the NSPs mainly migrated towards the HI lesion sites. The tangential, rostrocaudal migrations could be observed but impaired. These findings suggest that the NSP migratory pathways in SVZ change in response to the HI insult, likely due to the self-repairing efforts known in the neonatal brains. The MRI approach demonstrated here is potentially applicable to the in vivo and longitudinal study of NSP cell activities in developing brains under normal and pathological conditions and in therapeutic interventions. © 2009 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex