Increased transverse relaxivity in ultrasmall superparamagnetic iron oxide nanoparticles used as MRI contrast agent for biomedical imaging.

Synthesis of a contrast agent for biomedical imaging is of great interest where magnetic nanoparticles are concerned, because of the strong influence of particle size on transverse relaxivity. In the present study, biocompatible magnetic iron oxide nanoparticles were synthesized by co-precipitation of Fe2+ and Fe3+ salts, followed by surface adsorption with reduced dextran. The synthesized nanoparticles were spherical in shape, and 12 ± 2 nm in size as measured using transmission electron microscopy; this was corroborated with results from X-ray diffraction and dynamic light scattering studies. The nanoparticles exhibited superparamagnetic behavior, superior T2 relaxation rate and high relaxivities (r1 = 18.4 ± 0.3, r2 = 90.5 ± 0.8 s-1 mM-1 , at 7 T). MR image analysis of animals before and after magnetic nanoparticle administration revealed that the signal intensity of tumor imaging, specific organ imaging and whole body imaging can be clearly distinguished, due to the strong relaxation properties of these nanoparticles. Very low concentrations (3.0 mg Fe/kg body weight) of iron oxides are sufficient for early detection of tumors, and also have a clear distinction in pre- and post-enhancement of contrast in organs and body imaging. Many investigators have demonstrated high relaxivities of magnetic nanoparticles at superparamagnetic iron oxide level above 50 nm, but this investigation presents a satisfactory, ultrasmall, superparamagnetic and high transverse relaxivity negative contrast agent for diagnosis in pre-clinical studies. Copyright © 2016 John Wiley & Sons, Ltd.

Longitudinal changes in the DTI measures, anti-GFAP expression and levels of serum inflammatory cytokines following mild traumatic brain injury.

The majority of human mild traumatic brain injuries (mTBI; 70%) lack radiological evidence of injury, yet may present long term cognitive, and behavioral dysfunctions. With the hypothesis of evident damaged neural tissue and immunological consequences during acute phase of mTBI, we used closed skull weight-drop TBI model to address human mTBI condition. Serum cytokines (TNF-α, IL-10) and glial fibrillary acidic protein (GFAP) expression were examined at day 0 (control, pre-injury), 4h, day 1, day 3 and day 5 post injury (PI). Diffusion tensor imaging (DTI) was performed at similar timepoints to identify neuroinflammation translation into imaging abnormalities and monitor injury progression. DTI indices including mean diffusivity (MD), radial diffusivity (RD), fractional anisotropy and axial diffusivity values were quantified from cortex (CTX), hippocampus and corpus callosum regions. One way ANOVA showed significant increase in TNF-α at 4h and IL-10 at day 1 PI as compared to control. GFAP(+) cells were significantly increased at day 3 and day 5 as compared to control in CTX. Repeated measures ANOVA revealed significant decreases in MD, RD values in CTX at day 3 and day 5 as compared to day 0. A significant, inverse correlation was observed between cortical MD (r=-0.74, p=0.01), AD (r=-0.60, p=0.03) and RD (r=-0.72, p=0.01) values with mean GFAP(+) cells in the cortical region. These findings suggest that mTBI leads to elevated cytokine expression and subsequent hypertrophy of astrocytic processes. The increased numbers of reactive glial cells contribute diffusion restrictions in the CNS leading to reduced MD and RD values. These findings are in line with the deficits and pathologies associated with clinical mTBI, and support the use of mTBI model to address pathology and therapeutic options.

Transgene expression study of CXCR4 active mutants. Potential prospects in up-modulation of homing and engraftment efficiency of hematopoietic stem/progenitor cells.

Homing and engraftment, a determining factor in hematopoietic stem cell transplantation success is defined as a process through which hematopoietic stem/progenitor cells (HSPCs) lodge recipient bone marrow. SDF-1/CXCR4 axis acts as a principle regulator in homing and engraftment, however, CXCR4 signaling is dependent upon expression of CXCR4 and its ligand SDF-1, which is highly dynamic. Hence, present investigation was aimed to explore the potential of CXCR4 constitutive active mutants (CXCR4-CAMs) in overcoming the limitation of CXCR4 signaling and up-modulate its efficiency in homing and engraftment. Regulated transgene expression study of these mutants revealed their significantly enhanced cell adhesion efficiency to endothelium and extracellular matrix protein. This altogether indicates promising prospects of CXCR4-CAMs in research aimed to improve HSPCs engraftment efficiency.

Transparent magnesium aluminate spinel: a prospective biomaterial for esthetic orthodontic brackets.

Adult orthodontics is recently gaining popularity due to its importance in esthetics, oral and general health. However, none of the currently available alumina or zirconia based ceramic orthodontic brackets meet the esthetic demands of adult patients. Inherent hexagonal lattice structure and associated birefringence limits the visible light transmission in polycrystalline alumina and make them appear white and non transparent. Hence focus of the present study was to assess the feasibility of using magnesium aluminate (MgAl2O4) spinel; a member of the transparent ceramic family for esthetic orthodontic brackets. Transparent spinel specimens were developed from commercially available white spinel powder through colloidal shaping followed by pressureless sintering and hot isostatic pressing at optimum conditions of temperature and pressure. Samples were characterized for chemical composition, phases, density, hardness, flexural strength, fracture toughness and optical transmission. Biocompatibility was evaluated with in-vitro cell line experiments for cytotoxicity, apoptosis and genotoxicity. Results showed that transparent spinel samples had requisite physico-chemical, mechanical, optical and excellent biocompatibility for fabricating orthodontic brackets. Transparent spinel developed through this method demonstrated its possibility as a prospective biomaterial for developing esthetic orthodontic brackets.

11C-MET PET/CT and advanced MRI in the evaluation of tumor recurrence in high-grade gliomas.

OBJECTIVES: The purpose of this study was to evaluate the performance of l-[methyl-()11C]methionine (11C-MET) PET/CT and MRI (with the inclusion of advanced imaging techniques, namely, MR spectroscopy and MR perfusion) in the assessment of tumor recurrence in high-grade gliomas. PATIENTS AND METHODS: Twenty-nine patients with high-grade gliomas who underwent surgical resection, external beam radiation therapy, and standard regimens of chemotherapy were subjected to MRI (conventional, MR perfusion, and MR spectroscopy) and 11C-MET PET/CT scans. A definitive diagnosis was made based on histopathology and/or long-term clinical and radiological follow-up. Several indices were obtained for lesion characterization, namely, SUVmean, SUVmax, and mean lesion-to-normal tissue on PET/CT, as well as relative cerebral blood volume and choline-to-creatine ratio on MRI. RESULTS: Histological examination revealed viable tumor cells in 19 cases, whereas the remaining 10 were deemed to be negative based on histology (3 cases) or long-term follow-up (7 cases). All the quantitative indices mentioned previously tended to be higher in patients with tumor recurrence/residual. The sensitivity, specificity, and accuracy of 11C-MET PET/CT in identifying tumor recurrence/residual were 94.7%, 80%, and 89.6%, respectively, whereas that of MRI were 84.2%, 90%, and 86.2%, respectively. CONCLUSIONS: Both 11C-MET PET/CT and MRI (with the inclusion of advanced MRI techniques) demonstrated a high diagnostic performance in the identification of tumor residual/recurrence in high-grade gliomas posttherapy. Although 11C-MET PET/CT seemed to be more sensitive, whereas advanced MRI seemed more specific, there was no statistically significant difference in the diagnostic performance of either modality in the present study. Further studies with a larger group of patients are warranted.

Modification of radiation-induced DNA double strand break repair pathways by chemicals extracted from Podophyllum hexandrum: an in vitro study in human blood leukocytes.

Radiation exposure is a serious threat to biomolecules, particularly DNA, proteins and lipids. Various exogenous substances have been reported to protect these biomolecules. In this study we explored the effect of pre-treatment with G-002M, a mixture of three active derivatives isolated from the rhizomes of Podophyllum hexandrum, on DNA damage response in irradiated human blood leukocytes. Blood was collected from healthy male volunteers, preincubated with G-002M and then irradiated with various doses of radiation. Samples were analyzed using flow cytometry to quantify DNA double strand break (DSB) biomarkers including γ-H2AX, P53BP1 and levels of ligase IV. Blood samples were irradiated in vitro and processed to determine time and dose-dependent kinetics. Semiquantitative RT-PCR was performed at various time points to measure gene expression of DNA-PKcs, Ku80, ATM, and 53BP1; each of these genes is involved in DNA repair signaling. Pre-treatment of blood with G-002M resulted in reduction of γ-H2AX and P53BP1 biomarkers levels and elevated ligase IV levels relative to non-G-002M-treated irradiated cells. These results confirm suppression in radiation-induced DNA DSBs. Samples pre-treated with G-002M and then irradiated also showed significant up-regulation of DNA-PKcs and Ku80 and downregulation of ATM and 53BP1 gene expressions, suggesting that G-002M plays a protective role against DNA damage. The protective effect of G-002M may be due to its ability to scavange radiation-induced free radicals or assist in DNA repair. Further studies are needed to decipher the role of G-002M on signaling molecules involved in radiation-induced DNA damage repair pathways.

Laser ionization mass spectrometry in oral squamous cell carcinoma.

Biomarker research in oral squamous cell carcinoma (OSCC) aims for screening/early diagnosis and in predicting its recurrence, metastasis and overall prognosis. This article reviews the current molecular perspectives and diagnosis of oral cancer with proteomics using matrix-assisted laser desorption ionization (MALDI) and surface-enhanced laser desorption ionization (SELDI) mass spectrometry (MS). This method shows higher sensitivity, accuracy, reproducibility and ability to handle complex tissues and biological fluid samples. However, the data interpretation tools of contemporary mass spectrometry still warrant further improvement. Based on the data available with laser-based mass spectrometry, biomarkers of OSCC are classified as (i) diagnosis and prognosis, (ii) secretory, (iii) recurrence and metastasis, and (iv) drug targets. Majority of these biomarkers are involved in cell homeostasis and are either physiologic responders or enzymes. Therefore, proteins directly related to tumorigenesis have more diagnostic value. Salivary secretory markers are another group that offers a favourable and easy strategy for non-invasive screening and early diagnosis in oral cancer. Key molecular inter-related pathways in oral carcinogenesis are also intensely researched with software analysis to facilitate targeted drug therapeutics. The review suggested the need for incorporating 'multiple MS or tandem approaches' and focusing on a 'group of biomarkers' instead of single protein entities, for making early diagnosis and treatment for oral cancer a reality.

High throughput transcriptome profiling of lithium stimulated human mesenchymal stem cells reveals priming towards osteoblastic lineage.

Human mesenchymal stem cells (hMSCs) present in the bone marrow are the precursors of osteoblasts, chondrocytes and adipocytes, and hold tremendous potential for osteoregenerative therapy. However, achieving directed differentiation into osteoblasts has been a major concern. The use of lithium for enhancing osteogenic differentiation has been documented in animal models but its effect in humans is not clear. We, therefore, performed high throughput transcriptome analysis of lithium-treated hMSCs to identify altered gene expression and its relevance to osteogenic differentiation. Our results show suppression of proliferation and enhancement of alkaline phosphatase (ALP) activity upon lithium treatment of hMSCs under non-osteogenic conditions. Microarray profiling of lithium-stimulated hMSC revealed decreased expression of adipogenic genes (CEBPA, CMKLR1, HSD11B1) and genes involved in lipid biosynthesis. Interestingly, osteoclastogenic factors and immune responsive genes (IL7, IL8, CXCL1, CXCL12, CCL20) were also downregulated. Negative transcriptional regulators of the osteogenic program (TWIST1 and PBX1) were suppressed while genes involved in mineralization like CLEC3B and ATF4 were induced. Gene ontology analysis revealed enrichment of upregulated genes related to mesenchymal cell differentiation and signal transduction. Lithium priming led to enhanced collagen 1 synthesis and osteogenic induction of lithium pretreated MSCs resulted in enhanced expression of Runx2, ALP and bone sialoprotein. However, siRNA-mediated knockdown of RRAD, CLEC3B and ATF4 attenuated lithium-induced osteogenic priming, identifying a role for RRAD, a member of small GTP binding protein family, in osteoblast differentiation. In conclusion, our data highlight the transcriptome reprogramming potential of lithium resulting in higher propensity of lithium "primed" MSCs for osteoblastic differentiation.

Individual differences in trait anxiety are associated with white matter tract integrity in fornix and uncinate fasciculus: preliminary evidence from a DTI based tractography study.

Trait anxiety, a personality dimension that measures an individual's higher disposition to anxiety, has been found to be associated with many functional consequences viz. increased distractibility, attentional bias in favor of threat-related information etc. Similarly, volumetric studies have reported morphological changes viz. a decrease in the volume of left uncinate fasciculus (fiber connecting anterior temporal areas including the amygdala with prefrontal-/orbitofrontal cortices) and an increase in the volume of the left amygdala and right hippocampus, to be associated with trait anxiety. The functional and morphological changes associated with trait anxiety might also be associated with the changes in the integrity of WM tracts in relation with the trait anxiety levels of the subjects. Therefore, in the present diffusion tensor tractography (DTT) study, we investigated the possible relationship between the diffusion tensor imaging (DTI) derived indices of a wide array of fiber tracts and the trait anxiety scores in our subject group. A positive correlation between trait anxiety scores and the mean fractional anisotropy (FA) value was obtained in fornix and left uncinate fasciculus. The study provides first account of a positive relation between sub-clinical anxiety levels of subjects and the FA of fornix thereby providing interesting insights into the biological foundation of sub-clinical anxiety.

Differential biochemical response of rat kidney towards low and high doses of NiCl2 as revealed by NMR spectroscopy.

Heavy metals are known for their associated nephrotoxicity and nickel is no exception. An integrated metabonomic approach, based on high-resolution (1) H NMR spectroscopy, was applied to determine the acute biochemical effects of NiCl(2) on the renal tissues of rats. Kidney homogenates from rats treated with NiCl(2) at two dose levels (4 and 20 mg kg(-1) b.w., i.p.) and those from controls were analysed using (1) H NMR spectroscopy and also assessed for antioxidant parameters at days 1, 3 and 5 post-dose. The major metabolite changes corresponding to nickel exposure were related to amino acids, osmolytes and energy metabolites. Differential responses were observed in (1) H NMR spectra with exposure to low and high doses of NiCl(2). For high doses, (1) H NMR spectral analysis revealed alterations in renal tissues, along with damage to the cortical and papillary region and depletion of renal osmolytes such as betaine, trimethyl amine oxide, myo-inositol and taurine, which persisted until day 5 post-dose. The metabolite profile of (1) H NMR spectra obtained from animals treated with lower dose of NiCl(2) initially increased as an immediate stress response and then showed signs of recovery with the passage of time. NMR spectral analysis was well corroborated with histopathological and oxidative stress results. Nickel-induced oxidative stress was observed in both groups of animals with increased levels of antioxidant parameters at initial time points, but continued to increase in the high-dose group. The present study shows a huge potential of metabonomics for mapping organ-based metabolic response during heavy metal toxicity.

Radiation-induced early changes in the brain and behavior: serial diffusion tensor imaging and behavioral evaluation after graded doses of radiation.

The nuclear arsenal and the use of nuclear technologies have enhanced the likelihood of whole-body/partial-body radiation exposure. The central nervous system is highly susceptible to even low doses of radiation. With the aim of detecting and monitoring the pathologic changes of radiation-induced damage in brain parenchyma, we used serial diffusion tensor magnetic resonance imaging (DTI) with a 7T magnetic resonance unit and neurobehavioral assessments mice irradiated with 3-, 5-, and 8-Gy doses of radiation. Fractional anisotropy (FA) and mean diffusivity (MD) values at each time point (baseline, day 1, day 5, and day 10) were quantified from hippocampus, thalamus, hypothalamus, cudate-putamen, frontal cortex, sensorimotor cortex, corpus callosum, cingulum, and cerebral peduncle. Behavioral tests were performed at baseline, day 5, and day 10. A decrease in FA values with time was observed in all three groups. At day 10, dose-dependent decreases in FA and MD values were observed in all of the regions compared with baseline. Behavioral data obtained in this study correlate with FA values. Radiation-induced affective disorders were not radiation dose dependent, insofar as the anxiety-like symptoms at the lower dose (3 Gy) mimics to the symptoms with the higher dose (8 Gy) level but not with the moderate dose. However, there was a dose-dependent decline in cognitive function as well as FA values. Behavioral data support the DTI indices, so it is suggested that DTI may be a useful tool for noninvasive monitoring of radiation-induced brain injury.

F-18 FDG and C-11 methionine PET/CT in intracranial dural metastases.

A 58-year-old woman with breast carcinoma, after mastectomy, radiotherapy, and chemotherapy, underwent a whole-body F-18 FDG PET/CT for restaging, which revealed multiple skeletal metastasis. Hypometabolism was noted in the right frontal lobe. The patient subsequently underwent a C-11 methionine brain scan, which demonstrated multiple dural-based metastatic foci confirmed on contrast-enhanced MR. FDG PET has limitations in brain tumor detection. Amino acid tracers are particularly attractive for imaging of brain tumors because of relatively high tumor to brain activity ratios.

Principal eigenvector field segmentation for reproducible diffusion tensor tractography of white matter structures.

The study was aimed to test the feasibility of utilizing an algorithmically determinable stable fiber mass (SFM) map obtained by an unsupervised principal eigenvector field segmentation (PEVFS) for automatic delineation of 18 white matter (WM) tracts: (1) corpus callosum (CC), (2) tapetum (TP), (3) inferior longitudinal fasciculus (ILF), (4) uncinate fasciculus (UNC), (5) inferior fronto-occipital fasciculus (IFO), (6) optic pathways (OP), (7) superior longitudinal fasciculus (SLF), (8) arcuate fasciculus (AF), (9) fornix (FX), (10) cingulum (CG), (11) anterior thalamic radiation (ATR), (12) superior thalamic radiation (STR), (13) posterior thalamic radiation (PTR), (14) corticospinal/corticopontine tract (CST/CPT), (15) medial lemniscus (ML), (16) superior cerebellar peduncle (SCP), (17) middle cerebellar peduncle (MCP) and (18) inferior cerebellar peduncle (ICP). Diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) and the principal eigenvector field have been used to create the SFM consisting of a collection of linear voxel structures which are grouped together by color-coding them into seven natural classes to provide PEVFS signature segments which greatly facilitate the selection of regions of interest (ROIs) for fiber tractography using just a single mouse click, as compared with a manual drawing of ROIs in the classical approach. All the 18 fiber bundles have been successfully reconstructed, in all the subjects, using the single ROIs provided by the SFM approach, with their reproducibility characterized by the fact that the ROI selection is user independent. The essentially automatic PEVFS method is robust, efficient and compares favorably with the classical ROI methods for diffusion tensor tractography (DTT).

Radical scavenging and radiomodulatory effects of Psoralea corylifolia Linn. substantiated by in vitro assays and EPR spectroscopy.

The present study is the first report of the radiomodulatory effects of Psoralea corylifolia Linn. The extract (IBG-RA-26) prepared from P. corylifolia was chemically analysed by HPLC, LC-MS/MS and NMR. The total polyphenolic content of IBG-RA-26 was 0.287 mg/ml of quercetin equivalents. IBG-RA-26 exhibited a dose-dependent increase in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. It exhibited comparable (> 50%) site-specific and non-site-specific hydroxyl radical scavenging activity in higher concentration ranges (500-1000 microg/ml), while at lower concentrations (5-50 microg/ml) it exhibited significantly (p < 0.05) higher non-site-specific scavenging ability compared to site-specific activity. Nitric oxide scavenging activity of IBG-RA-26 (5-1000 microg/ml) increased in a concentration-dependent manner, while maximum superoxide ion scavenging ability (79%) was observed at 50 microg/ml. The electron donation potential of IBG-RA-26 was found to be higher than that of ascorbic acid at lower concentrations (up to 5 microg/ml). Analysis of the ability of IBG-RA-26 to protect membranes against gamma-radiation, utilizing an artificial membrane system (liposome), revealed a significant (p < 0.05) decrease in the formation of malondialdehyde (MDA) as a function of the concentration of IBG-RA-26. Radiation-induced lysis of human erythrocytes was monitored and efficacy of IBG-RA-26 was tested in the concentration range 25-1000 microg/ml, with significant protective efficacy observed in the range 25-50 microg/ml. IBG-RA-26 rendered significant (p < 0.05) protection against radiation (0.25 kGy)-induced DNA damage. EPR spectroscopy was used to investigate the DPPH radical scavenging capacity of IBG-RA-26. IBG-RA-26 exhibited a good DPPH radical scavenging capacity in a concentration-dependent manner. By direct EPR spectroscopy we have also demonstrated the possible formation of free radical species in a solution of IBG-RA-26. The wide spectrum of radioprotective and antioxidant properties exhibited by IBG-RA-26 indicate that P. corylifolia has potential as a radiomodulatory agent.

Study of acute biochemical effects of thallium toxicity in mouse urine by NMR spectroscopy.

Thallium (Tl) is a toxic heavy metal and its exposure to the human body causes physiological and biochemical changes due to its interference with potassium-dependent biological reactions. A high-resolution (1)H NMR spectroscopy based metabonomic approach has been applied for investigating acute biochemical effects caused by thallium sulfate (Tl(2)SO(4)). Male strain A mice were divided in three groups and received three doses of Tl(2)SO(4) (5, 10 and 20 mg kg(-1) b.w., i.p.). Urine samples collected at 3, 24, 72 and 96 h post-dose time points were analyzed by (1)H NMR spectroscopy. NMR spectral data were processed and analyzed using principal components analysis to represent biochemical variations induced by Tl(2)SO(4). Results showed Tl-exposed mice urine to have distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of treated groups. The metabolic signature of urine analysis from Tl(2)SO(4)-treated animals exhibited an increase in the levels of creatinine, taurine, hippurate and ß-hydroxybutyrate along with a decrease in energy metabolites trimethylamine and choline. These findings revealed Tl-induced disturbed gut flora, membrane metabolite, energy and protein metabolism, representing physiological dysfunction of vital organs. The present study indicates the great potential of NMR-based metabonomics in mapping metabolic response for toxicology, which could ultimately lead to identification of potential markers for Tl toxicity.

Intra-cavitary course of right coronary artery: what the cardiologists should be aware of!

We report an unusual case of an anomalous intra-cavitary course of the right coronary artery (RCA) that was detected on multislice computed tomography (CT) angiography. Albeit rare, this anomaly is being picked up with increasing frequency owing to the widespread use of coronary CT angiography (CCTA). Although this entity does not produce symptoms per se, it can result in potentially catastrophic complications during interventional procedures or bypass surgeries if not recognized in time.

Nuclear magnetic resonance spectroscopy-based metabonomic investigation of biochemical effects in serum of γ-irradiated mice.

PURPOSE: Radiation exposure induces change in many biological compounds. It is important to assess the physiological and biochemical response to an absorbed dose of ionising radiation due to intentional or accidental event and to predict medical consequences for medical management. In the present study, nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling was used in mice serum for identification of radiation-induced changes at metabolite level. MATERIALS AND METHODS: Mice were irradiated with 3, 5 and 8 Gray of γ-radiation dose and serum samples collected at day 1, 3 and 5 post irradiation were analysed by proton nuclear magnetic resonance (¹H NMR) spectroscopy. ¹H NMR spectra of serum were analysed by pattern recognition using principal component analysis. RESULTS: Irradiated mice serum showed distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of irradiated groups. ¹H NMR spectral analysis exhibited increased lactate, amino acids, choline and lipid signals as well as decreased glucose signals. These findings indicate radiation-induced disturbed energy, lipid and protein metabolism. CONCLUSIONS: The information obtained from this study reflects multiple physiological dysfunctions. The study promises the application of NMR-based metabonomics in the field of radiobiology, for development of metabolic-based markers for screening of risk populations and medical management in these cases.

Stromal-derived factor-1/CXCR4 signaling: indispensable role in homing and engraftment of hematopoietic stem cells in bone marrow.

Homing and engraftment of hematopoietic stem/progenitor cells (HSPCs) in bone marrow is the major determining factor in success of hematopoietic stem cell transplantation. This is a complex, multistep process orchestrated by the coordinated interplay between adhesion molecules, cytokines, growth factors, and regulatory cofactors, many of which remain to be defined. Recent studies have highlighted the pivotal role of unique stromal-derived factor-1 (SDF-1)/CXCR4 signaling in the regulation of HSPC homing and subsequent engraftment. In addition, studies suggest that SDF-1/CXCR4 signaling acts as an essential survival-promoting factor of transplanted HSPCs as well as maintenance of quiescent HSCs in bone marrow niche. These pleiotropic effects exerted by SDF-1/CXCR4 axis make this unique signaling initiator very promising, not only for optimal hematopoietic reconstitution but also for the development of innovative approaches to achieve restoration, regeneration, or repair of other damaged tissues potentially amendable to reversal by stem cell transplantation. This goal can only be achieved when the role of SDF-1/CXCR4 axis in hematopoietic transplantation is clearly defined. Hence, this review presents current knowledge of the mechanisms through which SDF-1/CXCR4 signaling promotes restoration of hematopoiesis by regulating the homing and engraftment of HSPCs.

Understanding development and lateralization of major cerebral fiber bundles in pediatric population through quantitative diffusion tensor tractography.

Region of interest based morphometric diffusion tensor imaging analysis, has been used extensively for the assessment of age-related changes in human brain, is limited to two dimensions and does not reflect the whole fiber bundle; however, diffusion tensor tractography (DTT) offers an overall view of individual fiber bundle in three-dimensional spaces. Quantitative DTT was performed on 51 healthy subjects of pediatric age range and young adults to compare age-related fractional anisotropy (FA) changes in corpus callosum, sensory and motor pathways, limbic tracts [cingulum (CNG) and fornix (Fx)], and superior and inferior longitudinal fascicules. In corpus callosum, inferior longitudinal fascicules, limbic tracts (CNG and Fx), sensory pathways, and motor pathways, an initial sharp increase in FA was observed up to the age of 2 y followed by a gradual increase up to 21 y. In superior longitudinal fascicules, sharp increase in FA was observed up to 3 y followed by a gradual increase. The FA value of the left CNG (p = 0.01, sign test) was observed to be significantly greater than that of the right CNG. We conclude that white matter fiber tracts mature with age and can be assessed by using DTT that may greatly improve our understanding of the human brain development.