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1.  Observed Personality in Childhood: Psychometric and Behavioral Genetic Evidence of Two Broad Personality Factors 
European journal of personality  2012;27(1):96-105.
We examined broad dimensions of children’s personalities (total n = 1056; age = 3.5 to 12 years) based on observers’ perceptions following a few hours of structured interaction. Siblings’ behaviors during a two-hour cognitive assessment in the home were rated separately by two different observers. Exploratory and confirmatory factor analyses clearly revealed a two-factor solution in three different samples. There was correspondence between parent-rated temperament and the observer-rated factors. Cross-sectional analyses indicated lower Plasticity among older children and higher Stability among older children. Sex differences were negligible. Plasticity and Stability were correlated in the .2 to .3 range. Most of the sibling similarity in the Plasticity was due to additive genetic influences, whereas most sibling similarity in Stability was attributable to shared environmental influences. The findings implicate a biometric factor structure to childhood personality that fits well with emerging bio-social theories of personality development.
PMCID: PMC4053248  PMID: 24932065
broad personality factor; observation; childhood; psychometric; behavioral genetics
2.  A robust multi-shot scan strategy for high-resolution diffusion weighted MRI enabled by multiplexed sensitivity-encoding (MUSE) 
NeuroImage  2013;72:41-47.
Diffusion weighted magnetic resonance imaging (DWI) data have been mostly acquired with single-shot echo-planar imaging (EPI) to minimize motion induced artifacts. The spatial resolution, however, is inherently limited in single-shot EPI, even when the parallel imaging (usually at an acceleration factor of 2) is incorporated. Multi-shot acquisition strategies could potentially achieve higher spatial resolution and fidelity, but they are generally susceptible to motion-induced phase errors among excitations that are exacerbated by diffusion sensitizing gradients, rendering the reconstructed images unusable. It has been shown that shot-to-shot phase variations may be corrected using navigator echoes, but at the cost of imaging throughput. To address these challenges, a novel and robust multi-shot DWI technique, termed multiplexed sensitivity-encoding (MUSE), is developed here to reliably and inherently correct nonlinear shot-to-shot phase variations without the use of navigator echoes. The performance of the MUSE technique is confirmed experimentally in healthy adult volunteers on 3 Tesla MRI systems. This newly developed technique should prove highly valuable for mapping brain structures and connectivities at high spatial resolution for neuroscience studies.
PMCID: PMC3602151  PMID: 23370063
diffusion weighted imaging; inherent phase correction; multiplexed sensitivity-encoding; interleaved echo-planar imaging; multi-shot echo-planar imaging
3.  Optimal Continuous-Monitoring Design of Single-arm Phase II Trial Based on the Simulated Annealing Method 
Contemporary clinical trials  2013;35(1):170-178.
Simon’s two-stage design is commonly used in phase II single-arm clinical trials because of its simplicity and smaller sample size under the null hypothesis compared to the one-stage design. Some studies extend this design to accommodate more interim analyses (i.e., three-stage or four-stage designs). However, most of these studies, together with the original Simon’s two-stage design, are based on the exhaustive search method, which is difficult to extend to high-dimensional, general multi-stage designs. In this study, we propose a simulated annealing (SA)-based design to optimize the early stopping boundaries and minimize the expected sample size for multi-stage or continuous monitoring single-arm trials. We compare the results of the SA method, the decision-theoretic method, the predictive probability method, and the posterior probability method. The SA method can reach the smallest expected sample sizes in all scenarios under the constraints of the same type I and type II errors. The expected sample sizes from the SA method are generally 10–20% smaller than those from the posterior probability method or the predictive probability method, and are slightly smaller than those from the decision-theoretic method in almost all scenarios. The SA method offers an excellent alternative in designing phase II trials with continuous monitoring.
PMCID: PMC3741066  PMID: 23545075
Simulated annealing; Simon’s design; Early stopping; Adaptive design; Bayesian inference; Phase II trial; Type I error; Type II error; Optimal design
4.  The Mechanism of Poly-Galloyl-Glucoses Preventing Influenza A Virus Entry into Host Cells 
PLoS ONE  2014;9(4):e94392.
Hemagglutinin (HA) is essential for Influenza A virus infection, but its diversity of subtypes presents an obstacle to developing broad-spectrum HA inhibitors. In this study, we investigated the molecular mechanisms by which poly-galloyl glucose (pGG) analogs inhibit influenza hemagglutinin (HA) in vitro and in silico. We found that (1) star-shaped pGG analogs exhibit HA-inhibition activity by interacting with the conserved structural elements of the receptor binding domain (RBD); (2) HA inhibition depends on the number of galloyl substituents in a pGG analog; the best number is four; and when PGG binds with two HA trimers at their conserved receptor binding domains (loop 130, loop 220, and 190-α-helix), PGG acts as a molecular glue by aggregating viral particles so as to prevent viral entry into host cells (this was revealed via an in silico simulation on the binding of penta-galloyl-glucose (PGG) with HA). pGGs are also effective on a broad-spectrum influenza A subtypes (including H1, H3, H5, H7); this suggests that pGG analogs can be applied to most influenza A subtypes as a prophylactic against influenza viral infections.
PMCID: PMC3981784  PMID: 24718639
5.  Laparoscopic versus Open Hepatectomy with or without Synchronous Colectomy for Colorectal Liver Metastasis: A Meta-Analysis 
PLoS ONE  2014;9(1):e87461.
To compare short-term and long-term results of colorectal patients undergoing laparoscopic and open hepatectomy. Moreover, outcomes of laparoscopic versus open procedures for simultaneous primary colorectal tumor and liver metastasis resection were compared.
A systematic search was conducted in the PubMed and EmBase databases (until Oct. 22. 2013) with no limits. Bibliographic citation management software (EndNote X6) was used for extracted literature management. Quality assessment was performed according to a modification of the Newcastle-Ottawa Scale. The data were analyzed using Review Manager (Version 5.1), and sensitivity analysis was performed by sequentially omitting each study.
Finally, 14 studies, including a total of 975 CLM (colorectal liver metastasis) patients, compared laparoscopic with open hepatectomy. 3 studies of them, including a total of 107 CLM patients, compared laparoscopic with open procedures for synchronous hepatectomy and colectomy. Laparoscopic hepatectomy was associated with a significantly less blood loss, shorter hospitalization time, and less operative transfusion rate. In addition, lower hospital morbidity rate (OR = 0.57, 95%CI:0.42–0.78, P = 0.0005) and better R0 resection (OR = 2.44, 95%CI:1.21–4.94, P = 0.01) were observed in laparoscopic hepatectomy. For long-term outcomes, there were no significant differences between two surgical procedures on recurrence and overall survival. In comparison of synchronous hepatectomy and colectomy, laparoscopic procedure displayed shorter hospitalization (MD = −3.40, 95%CI:−4.37–2.44, P<0.00001) than open procedure. Other outcomes, including surgical time, estimated blood loss, hospital morbidity, and overall survival did not differ significantly in the comparison.
Laparoscopic hepatectomy with or without synchronous colectomy are acceptable for selective CLM patients. We suggest standard inclusion criteria of CLM patients be formulated.
PMCID: PMC3906170  PMID: 24489916
6.  Open resection for lung cancer in right upper lobe 
Journal of Thoracic Disease  2013;5(6):862-863.
An open radical surgery for lung cancer of the right upper lobe is performed under suitable conditions in this case. According to the actual conditions, the horizontal fissure is made a “tunnel” dissociation during the operation to fully expose hilar structures (artery, vein, and bronchus). Since intraoperative frozen section diagnosis shows malignant result, lymph nodes are dissected. Hemostasis, protection of the important peripheral organs and standard postoperative placement of drainage tube should be noted. The observability of this surgery is the clear exposure and brief operation.
PMCID: PMC3886690  PMID: 24409367
Open resection; lung cancer; right upper lobe
7.  Phase II trial design with Bayesian adaptive randomization and predictive probability 
Journal of the Royal Statistical Society. Series C, Applied statistics  2012;61(2):10.1111/j.1467-9876.2011.01006.x.
We propose a randomized phase II clinical trial design based on Bayesian adaptive randomization and predictive probability monitoring. Adaptive randomization assigns more patients to a more efficacious treatment arm by comparing the posterior probabilities of efficacy between different arms. We continuously monitor the trial by using the predictive probability. The trial is terminated early when it is shown that one treatment is overwhelmingly superior to others or that all the treatments are equivalent. We develop two methods to compute the predictive probability by considering the uncertainty of the sample size of the future data. We illustrate the proposed Bayesian adaptive randomization and predictive probability design by using a phase II lung cancer clinical trial, and we conduct extensive simulation studies to examine the operating characteristics of the design. By coupling adaptive randomization and predictive probability approaches, the trial can treat more patients with a more efficacious treatment and allow for early stopping whenever sufficient information is obtained to conclude treatment superiority or equivalence. The design proposed also controls both the type I and the type II errors and offers an alternative Bayesian approach to the frequentist group sequential design.
PMCID: PMC3832255  PMID: 24259753
Adaptive randomization; Bayesian inference; Clinical trial ethics; Group sequential method; Posterior predictive distribution; Randomized trial; Type I error; Type II error
8.  Autophagy Restricts Proliferation Driven By Oncogenic Phosphatidylinositol 3-Kinase in Three-Dimensional Culture 
Oncogene  2012;32(20):2543-2554.
Autophagy is a tightly regulated lysosomal self-digestion process that can both promote and impede tumorigenesis. Here, we utilize a three-dimensional (3D) culture model to address how interactions between autophagy and the PI3K/Akt/mTOR pathway impact the malignant behavior of cells carrying a tumor-derived, activating mutation in PI3K (PI3K-H1047R). In this model, autophagy simultaneously mediates tumor suppressive and promoting functions within individual glandular structures. In 3D culture, constitutive PI3K activation overcomes proliferation arrest and promotes resistance to anoikis in the luminal space, resulting in aberrant structures with filled lumen. Inhibiting autophagy in PI3K-H1047R structures triggers luminal cell apoptosis, resulting in lumen clearance. At the same time, ATG depletion strongly enhances PI3K-H1047R cell proliferation during 3D morphogenesis, revealing an unexpected role for autophagy in restricting proliferation driven by PI3K activation. Intriguingly, over-expression of the autophagy cargo receptor p62/SQSTM1 in PI3K-H1047R cells is sufficient to enhance cell proliferation, activate the ERK/MAPK pathway, and to promote EGF-independent proliferation in 3D culture. Overall, these results indicate that autophagy antagonizes specific aspects of oncogenic PI3K transformation, with the loss of autophagy promoting proliferation.
PMCID: PMC3470740  PMID: 22777351
Autophagy; oncogenic PI3K; proliferation; 3D culture
9.  Distinct Metabolic Profile of Primary Focal Segmental Glomerulosclerosis Revealed by NMR-Based Metabolomics 
PLoS ONE  2013;8(11):e78531.
Primary focal segmental glomerulosclerosis (FSGS) is pathological entity which is characterized by idiopathic steroid-resistant nephrotic syndrome (SRNS) and progression to end-stage renal disease (ESRD) in the majority of affected individuals. Currently, there is no practical noninvasive technique to predict different pathological types of glomerulopathies. In this study, the role of urinary metabolomics in the diagnosis and pathogenesis of FSGS was investigated.
NMR-based metabolomics was applied for the urinary metabolic profile in the patients with FSGS (n = 25), membranous nephropathy (MN, n = 24), minimal change disease (MCD, n = 14) and IgA nephropathy (IgAN, n = 26), and healthy controls (CON, n = 35). The acquired data were analyzed using principal component analysis (PCA) followed by orthogonal projections to latent structure discriminant analysis (OPLS-DA). Model validity was verified using permutation tests.
FSGS patients were clearly distinguished from healthy controls and other three types of glomerulopathies with good sensitivity and specificity based on their global urinary metabolic profiles. In FSGS patients, urinary levels of glucose, dimethylamine and trimethylamine increased compared with healthy controls, while pyruvate, valine, hippurate, isoleucine, phenylacetylglycine, citrate, tyrosine, 3-methylhistidine and β-hydroxyisovalerate decreased. Additionally, FSGS patients had lower urine N-methylnicotinamide levels compared with other glomerulopathies.
NMR-based metabonomic approach is amenable for the noninvasive diagnosis and differential diagnosis of FSGS as well as other glomerulopathies, and it could indicate the possible mechanisms of primary FSGS.
PMCID: PMC3823857  PMID: 24244321
10.  SUMOylation of PPARγ by Rosiglitazone Prevents LPS-Induced NCoR Degradation Mediating Down Regulation of Chemokines Expression in Renal Proximal Tubular Cells 
PLoS ONE  2013;8(11):e79815.
Rosiglitazone (RGL), a synthetic agonist for peroxisome proliferator activated receptor γ (PPARγ), exhibits a potent anti-inflammatory activity by attenuating local infiltration of neutrophils and monocytes in the renal interstitium. To evaluate the mechanisms that account for inhibiting inflammatory cells infiltration, we investigated the effect of RGL on chemokines secretion and nuclear factor-kappa B (NF-κB) activation in human renal proximal tubular cells (PTCs). We demonstrated that RGL significantly inhibited lipopolysaccharide (LPS)-induced interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) production in a dose-dependent manner, without appreciable cytotoxicity. Chromatin immunoprecipitation (ChIP) assays clearly revealed that, RGL inhibited p65 binding to IL-8/MCP-1 gene promoters in LPS-stimulated PTCs. Interestingly, further experiments showed RGL reversed LPS-induced nuclear receptor corepressor (NCoR) degradation. In addition, knockdown of protein inhibitor of activated STAT1 (PIAS1), an indispensable small ubiquitin-like modifier (SUMO) ligase, abrogated the effects of RGL on antagonizing LPS-induced IL-8/MCP-1 overexpression and NCoR degradation. These findings suggest that, RGL activates PPARγ SUMOylation, inhibiting NCoR degradation and NF-κB activation in LPS-stimulated PTCs, which in turn decrease chemokines expression. The results unveil a new mechanism triggered by RGL for prevention of tubular inflammatory injury.
PMCID: PMC3832667  PMID: 24260304
11.  Interlayer interactions in graphites 
Scientific Reports  2013;3:3046.
Based on ab initio calculations of both the ABC- and AB-stacked graphites, interlayer potentials (i.e., graphene-graphene interaction) are obtained as a function of the interlayer spacing using a modified Möbius inversion method, and are used to calculate basic physical properties of graphite. Excellent consistency is observed between the calculated and experimental phonon dispersions of AB-stacked graphite, showing the validity of the interlayer potentials. More importantly, layer-related properties for nonideal structures (e.g., the exfoliation energy, cleave energy, stacking fault energy, surface energy, etc.) can be easily predicted from the interlayer potentials, which promise to be extremely efficient and helpful in studying van der Waals structures.
PMCID: PMC3818654  PMID: 24192753
12.  Investigation of the PSF-Choice method for reduced lipid contamination in prostate MRSI 
The purpose of this work was to evaluate a previously proposed approach that aims to improve the point-spread-function (PSF) of MR spectroscopic imaging (MRSI) in order to avoid corruption by lipid signal arising from neighboring voxels. Retrospective spatial filtering can be used to alter the PSF, however, this either reduces spatial resolution or requires extending the acquisition in k-space at the cost of increased imaging time. Alternatively, the method evaluated here, PSF-Choice, can modify the PSF localization to reduce the contamination from adjacent lipids by conforming the signal response more closely to the desired MRSI voxel grid. This is done without increasing scan time or degrading SNR of important metabolites. PSF-Choice achieves improvements in spatial localization through modifications to the RF excitation pulses. An implementation of this method is reported for MRSI of the prostate, where it is demonstrated that, in 13 of 16 pilot prostate MRSI scans, intra-voxel spectral contamination from lipid was significantly reduced when using PSF-Choice. Phantom studies were also performed that demonstrate, compared to MRSI with standard Fourier phase encoding, out-of-voxel signal contamination of spectra was significantly reduced in MRSI with PSF-Choice.
PMCID: PMC3435467  PMID: 22648701
point-spread-function (PSF); MR spectroscopic imaging (MRSI); prostate imaging; truncation artifact
13.  Inherent Correction of Motion-Induced Phase Errors in Multi-Shot Spiral Diffusion-Weighted Imaging 
Multi-shot spiral imaging is a promising alternative to echo-planar imaging for high-resolution diffusion-weighted imaging and diffusion tensor imaging. However, subject motion in the presence of diffusion-weighting gradients causes phase inconsistencies among different shots, resulting in signal loss and aliasing artifacts in the reconstructed images. Such artifacts can be reduced by using a variable-density spiral trajectory or a navigator echo, however at the cost of a longer scan time. Here, a novel iterative phase correction method is proposed to inherently correct for the motion-induced phase errors without requiring any additional scan time. In this initial study, numerical simulations and in vivo experiments are performed to demonstrate that the proposed method can effectively and efficiently correct for spatially linear phase errors caused by rigid-body motion in multi-shot spiral diffusion-weighted imaging of the human brain.
PMCID: PMC3323687  PMID: 22222689
inherent; motion correction; multi-shot; spiral; diffusion-weighted imaging
14.  Maternal Executive Function, Harsh Parenting, and Child Conduct Problems 
Maternal executive function and household regulation both are critical aspects of optimal childrearing, but their interplay is not understood. We tested the hypotheses that 1) the link between challenging child conduct problems and harsh parenting would be strongest for mothers with poorer executive function and weakest among those with better executive function, and 2) this mechanism would be further moderated by the degree of household chaos.
The socioeconomically diverse sample included 147 mothers of 3-to-7 year old children. Mothers completed questionnaires and a laboratory assessment of executive function.
Consistent with hypotheses, harsh parenting was linked with child conduct problems only among mothers with poorer executive function. This effect was particularly strong in calm, predictable environments, but was not evident in chaotic environments.
Maternal executive function is critical to minimizing harsh parenting in the context of challenging child behavior, but this self-regulation process may not operate well in chaotic environments.
PMCID: PMC3460037  PMID: 22764829
parenting; executive function; emotion regulation; conduct problems
15.  Functional MRI Using Regularized Parallel Imaging Acquisition 
Parallel MRI techniques reconstruct full-FOV images from undersampled k-space data by using the uncorrelated information from RF array coil elements. One disadvantage of parallel MRI is that the image signal-to-noise ratio (SNR) is degraded because of the reduced data samples and the spatially correlated nature of multiple RF receivers. Regularization has been proposed to mitigate the SNR loss originating due to the latter reason. Since it is necessary to utilize static prior to regularization, the dynamic contrast-to-noise ratio (CNR) in parallel MRI will be affected. In this paper we investigate the CNR of regularized sensitivity encoding (SENSE) acquisitions. We propose to implement regularized parallel MRI acquisitions in functional MRI (fMRI) experiments by incorporating the prior from combined segmented echo-planar imaging (EPI) acquisition into SENSE reconstructions. We investigated the impact of regularization on the CNR by performing parametric simulations at various BOLD contrasts, acceleration rates, and sizes of the active brain areas. As quantified by receiver operating characteristic (ROC) analysis, the simulations suggest that the detection power of SENSE fMRI can be improved by regularized reconstructions, compared to unregularized reconstructions. Human motor and visual fMRI data acquired at different field strengths and array coils also demonstrate that regularized SENSE improves the detection of functionally active brain regions.
PMCID: PMC3779863  PMID: 16032694
fMRI; SENSE; EPI; parallel MRI; brain
Outcome-adaptive randomization (AR) allocates more patients to the better treatments as the information accumulates in the trial. Is it worth to apply outcome-AR in clinical trials? Different views permeate the medical and statistical communities. We provide additional insights to the question by conducting extensive simulation studies. Trials are designed to maintain the type I error rate, achieve a specified power, and provide better treatment to patients. Generally speaking, equal randomization (ER) requires a smaller sample size and yields a smaller number of non-responders than AR by controlling type I and type II errors. Conversely, AR produces a higher overall response rate than ER with or without expanding the trial to the same maximum sample size. When there exist substantial treatment differences, AR can yield a higher overall response rate as well as a lower average sample size and a smaller number of non-responders. Similar results are found for the survival endpoint. The differences between AR and ER quickly diminish with early stopping of a trial due to efficacy or futility. In summary, ER maintains balanced allocation throughout the trial and reaches the specified statistical power with a smaller number of patients in the trial. If the trial’s result is positive, ER may lead to early approval of the treatment. AR focuses on treating patients best in the trial. AR may be preferred when the difference in efficacy between treatments is large or when limited patients are available.
PMCID: PMC3495976  PMID: 22753588
Adaptive and fixed randomization; Bayesian clinical trial design; Efficacy and futility early stopping; Type I error and statistical power; Patient population; Sample size
18.  Functional Brain Connectivity and Cognition: Effects of Adult Age and Task Demands 
Neurobiology of aging  2013;34(8):1925-1934.
Previous neuroimaging research has documented that patterns of intrinsic (resting-state) functional connectivity (FC) among brain regions covary with individual measures of cognitive performance. Here, we examined the relation between intrinsic FC and a reaction time (RT) measure of performance, as a function of both age group and task demands. We obtained filtered, event-related functional magnetic resonance imaging (fMRI) data, and RT measures of visual search performance, from 21 younger adults (19–29 years) and 21 healthy, older adults (60–87 years). Age-related decline occurred in the connectivity strength in multiple brain regions, consistent with previous findings. Among eight pairs of regions, across somatomotor, orbitofrontal, and subcortical networks, increasing FC was associated with faster responding (lower RT). Relative to younger adults, older adults exhibited a lower strength of this RT-connectivity relation and greater disruption of this relation by a salient but irrelevant display item (color singleton distractor). Age-related differences in the covariation of intrinsic FC and cognitive performance vary as a function of task demands.
PMCID: PMC3674832  PMID: 23523269
brain connectivity; fMRI; resting state; default mode; behavior-based connectivity analysis; aging; attention; cognition; visual search; reaction time
20.  Association of intercellular adhesion molecular-1 gene polymorphism in ischemic stroke patients 
Ischemic stroke (IS) is a prevalent disease causing a body disability, the third leading cause of death in Taiwan. It shows that the level of intercellular adhesion molecular-1 (ICAM-1) in IS patients is higher than control subjects.
This study is to investigate the possible association of ICAM-1 (G1548A) polymorphism in IS patients.
Materials and Methods:
A total of 646 subjects were enrolled in this study, including 312 IS patients, and 334 controls without a history of symptomatic IS. The ICAM-1 (G1548A) polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. Clinical factors were also determined.
The frequencies of the ICAM-1 (G1548A) polymorphism for G/G, G/A, and A/A were 74.8%, 23.9%, and 0.3%, respectively, in healthy controls, and 62.8%, 32.1%, and 5.1%, respectively, in patients. The frequency of the ICAM-1 (G1548A) A allele (21.2% versus 13.2%, respectively; P = 0.007) and the carriers of the ICAM-1 (G1548A) A allele (37.2% versus 25.2%; P = 0.019, OR 1.76, 95% CI 1.1-2.83) are great in IS patients compared with healthy controls. There is a higher risk of IS associated with homozygosity for the ICAM-1 (G1548A) A allele (AA genotype) compared with the control population (5.1% vs. 0.3%, respectively, P = 0.04; OR 5.1, 95% CI 1.19-21.66). We also observed both hypertension and diabetes has shown a positive association with IS.
The ICAM-1 (G1548A) polymorphism was associated with independent risk factor for the development of IS.
PMCID: PMC3788285  PMID: 24101821
Allele; intercellular adhesion molecular-1; ischemic stroke; polymorphism
21.  Socioeconomic Risk Moderates the Link between Household Chaos and Maternal Executive Function 
Journal of Family Psychology  2012;26(3):391-399.
We examined the link between household chaos (i.e., noise, clutter, disarray, lack of routines) and maternal executive function (i.e., effortful regulation of attention and memory), and whether it varied as a function of socioeconomic risk (i.e., single parenthood, lower mother and father educational attainment, housing situation, and father unemployment). We hypothesized that: 1) higher levels of household chaos would be linked with poorer maternal executive function, even when controlling for other measures of cognitive functioning (e.g., verbal ability), and 2) this link would be strongest in the most socioeconomically distressed or lowest-socioeconomic status households. The diverse sample included 153 mothers from urban and rural areas who completed a questionnaire and a battery of cognitive executive function tasks and a verbal ability task in the laboratory. Results were mixed for hypothesis 1, and consistent with hypothesis 2. Two-thirds of the variance overlapped between household chaos and maternal executive function, but only in families with high levels of socioeconomic risk. This pattern was not found for chaos and maternal verbal ability, suggesting that the potentially deleterious effects of household chaos may be specific to maternal executive function. The findings implicate household chaos as a powerful statistical predictor of maternal executive function in socioeconomically distressed contexts.
PMCID: PMC3368074  PMID: 22563703
parenting; executive function; environment; socioeconomic status
22.  Alterations in Brain Transition Metals in Huntington Disease 
Archives of neurology  2012;69(7):887-893.
Aberrant accumulation of transition metals in the brain may have an early and important role in the pathogenesis of several neurodegenerative disorders, including Huntington disease (HD).
To comprehensively evaluate and validate the distribution of metal deposition in the brain using advanced magnetic resonance imaging methods from the premanifest through symptomatic stages of HD.
Observational study.
University imaging center.
Twenty-eight HD expanded gene carriers, 34 patients with symptomatic HD, and 56 age- and sex-matched healthy control subjects were included in the study.
Participants underwent magnetic resonance imaging for the quantification of the phase evolution of susceptibility-weighted images.
Main Outcome Measures
To verify the identity of the metals responsible for the changes in the phase evolution of the susceptibility signal in the brain and to assess correlations with systemic levels. Inductively coupled plasma mass spectrometry was used to measure transition metal concentrations in postmortem brains.
In the basal ganglia, progressive increases in the phase evolution were found in HD, beginning in pre-manifest individuals who were far from expected onset and increasing with proximity to expected onset and thereafter. Increases in the cerebral cortex were regionally selective and present only in symptomatic HD. Increases were verified by excessive deposition of brain iron, but a complex alteration in other transition metals was found.
An important and early role of altered metal homeostasis is suggested in the pathogenesis of HD.
PMCID: PMC3652228  PMID: 22393169
23.  PROPELLER EPI: An MRI Technique Suitable for Diffusion Tensor Imaging at High Field Strength With Reduced Geometric Distortions 
A technique suitable for diffusion tensor imaging (DTI) at high field strengths is presented in this work. The method is based on a periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) k-space trajectory using EPI as the signal readout module, and hence is dubbed PROPELLER EPI. The implementation of PROPELLER EPI included a series of correction schemes to reduce possible errors associated with the intrinsically higher sensitivity of EPI to off-resonance effects. Experimental results on a 3.0 Tesla MR system showed that the PROPELLER EPI images exhibit substantially reduced geometric distortions compared with single-shot EPI, at a much lower RF specific absorption rate (SAR) than the original version of the PROPELLER fast spin-echo (FSE) technique. For DTI, the self-navigated phase-correction capability of the PROPELLER EPI sequence was shown to be effective for in vivo imaging. A higher signal-to-noise ratio (SNR) compared to single-shot EPI at an identical total scan time was achieved, which is advantageous for routine DTI applications in clinical practice.
PMCID: PMC3602792  PMID: 16206142
PROPELLER imaging; EPI; geometric distortions; specific absorption rate; diffusion tensor imaging
24.  Diffusion Tensor Imaging of Cerebral White Matter Integrity in Cognitive Aging 
Biochimica et Biophysica Acta  2011;1822(3):386-400.
In this article we review recent research on diffusion tensor imaging (DTI) of white matter (WM) integrity and the implications for age-related differences in cognition. Neurobiological mechanisms defined from DTI analyses suggest that a primary dimension of age-related decline in WM is a decline in the structural integrity of myelin, particularly in brain regions that myelinate later developmentally. Research integrating behavioral measures with DTI indicates that WM integrity supports the communication among cortical networks, particularly those involving executive function, perceptual speed, and memory (i.e., fluid cognition). In the absence of significant disease, age shares a substantial portion of the variance associated with the relation between WM integrity and fluid cognition. Current data are consistent with one model in which age-related decline in WM integrity contributes to a decreased efficiency of communication among networks for fluid cognitive abilities. Neurocognitive disorders for which older adults are at risk, such as depression, further modulate the relation between WM and cognition, in ways that are not as yet entirely clear. Developments in DTI technology are providing new insight into both the neurobiological mechanisms of aging WM and the potential contribution of DTI to understanding functional measures of brain activity.
PMCID: PMC3241892  PMID: 21871957
Magnetic resonance imaging; Brain; Behavior; Adult development; Neuroaxonal damage
25.  Investigation of long-term reproducibility of intrinsic connectivity network mapping: A resting-state fMRI study 
Connectivity mapping based on resting-state fMRI is rapidly developing and this methodology has great potential for clinical applications. However, before resting-state fMRI can be applied for diagnosis, prognosis, and monitoring treatment for an individual patient with neurologic or psychiatric diseases, it is essential to assess its long-term reproducibility and between-subject variations among healthy individuals. The purpose of the study is to (1) quantify the long-term test-retest reproducibility of intrinsic connectivity network (ICN) measures derived from resting-state fMRI, and (2) assess the between-subject variation of ICN measures across the whole brain.
Longitudinal resting-state fMRI data of six healthy volunteers were acquired from nine scan sessions over a period of more than one year. The within-subject reproducibility and between-subject variation of ICN measures, across 1) the whole brain and 2) major nodes of the default mode network, were quantified with intraclass correlation coefficient (ICC) and coefficient of variance (COV).
Our data show that the long-term test-retest reproducibility of ICN measures is outstanding, with over 70% of the connectivity networks showing an ICC greater than 0.60. COV across six healthy volunteers in this sample was greater than 0.2, suggesting significant between-subject variation.
Our data indicate that resting-state ICN measures (e.g., the correlation coefficients between fMRI signal profiles from two different brain regions) are potentially suitable as biomarkers for monitoring disease progression and treatment effects in clinical trials and individual patients. Because between-subject variation is significant, it may be difficult to use quantitative ICN measures, in their current state, as a diagnostic tool.
PMCID: PMC3584561  PMID: 22268094

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