Evaluation of highly accelerated simultaneous multi-slice EPI for fMRI.

Echo planar imaging (EPI) is the MRI technique that is most widely used for blood oxygen level-dependent (BOLD) functional MRI (fMRI). Recent advances in EPI speed have been made possible with simultaneous multi-slice (SMS) methods which combine acceleration factors M from multiband (MB) radiofrequency pulses and S from simultaneous image refocusing (SIR) to acquire a total of N=S×M images in one echo train, providing up to N times speed-up in total acquisition time over conventional EPI. We evaluated accelerations as high as N=48 using different combinations of S and M which allow for whole brain imaging in as little as 100ms at 3T with a 32 channel head coil. The various combinations of acceleration parameters were evaluated by tSNR as well as BOLD contrast-to-noise ratio (CNR) and information content from checkerboard and movie clips in fMRI experiments. We found that at low acceleration factors (N≤6), setting S=1 and varying M alone yielded the best results in all evaluation metrics, while at acceleration N=8 the results were mixed using both S=1 and S=2 sequences. At higher acceleration factors (N>8), using S=2 yielded maximal BOLD CNR and information content as measured by classification of movie clip frames. Importantly, we found significantly greater BOLD information content using relatively fast TRs in the range of 300ms-600ms compared to a TR of 2s, suggesting that faster TRs capture more information per unit time in task based fMRI.

Effects of image reconstruction on fiber orientation mapping from multichannel diffusion MRI: reducing the noise floor using SENSE.

PURPOSE: To examine the effects of the reconstruction algorithm of magnitude images from multichannel diffusion MRI on fiber orientation estimation. THEORY AND METHODS: It is well established that the method used to combine signals from different coil elements in multichannel MRI can have an impact on the properties of the reconstructed magnitude image. Using a root-sum-of-squares approach results in a magnitude signal that follows an effective noncentral-χ distribution. As a result, the noise floor, the minimum measurable in the absence of any true signal, is elevated. This is particularly relevant for diffusion-weighted MRI, where the signal attenuation is of interest. RESULTS: In this study, we illustrate problems that such image reconstruction characteristics may cause in the estimation of fiber orientations, both for model-based and model-free approaches, when modern 32-channel coils are used. We further propose an alternative image reconstruction method that is based on sensitivity encoding (SENSE) and preserves the Rician nature of the single-channel, magnitude MR signal. We show that for the same k-space data, root-sum-of-squares can cause excessive overfitting and reduced precision in orientation estimation compared with the SENSE-based approach. CONCLUSION: These results highlight the importance of choosing the appropriate image reconstruction method for tractography studies that use multichannel receiver coils for diffusion MRI acquisition.

The Human Connectome Project: a data acquisition perspective.

The Human Connectome Project (HCP) is an ambitious 5-year effort to characterize brain connectivity and function and their variability in healthy adults. This review summarizes the data acquisition plans being implemented by a consortium of HCP investigators who will study a population of 1200 subjects (twins and their non-twin siblings) using multiple imaging modalities along with extensive behavioral and genetic data. The imaging modalities will include diffusion imaging (dMRI), resting-state fMRI (R-fMRI), task-evoked fMRI (T-fMRI), T1- and T2-weighted MRI for structural and myelin mapping, plus combined magnetoencephalography and electroencephalography (MEG/EEG). Given the importance of obtaining the best possible data quality, we discuss the efforts underway during the first two years of the grant (Phase I) to refine and optimize many aspects of HCP data acquisition, including a new 7T scanner, a customized 3T scanner, and improved MR pulse sequences.

Single-shot 3D GRASE with cylindrical k-space trajectories.

Development of GRASE (gradient- and spin-echo) pulse sequences for single-shot 3D imaging has been motivated by physiologic studies of the brain. The duration of echo-planar imaging (EPI) subsequences between RF refocusing pulses in the GRASE sequence is determinant of image distortions and susceptibility artifacts. To reduce these artifacts the regular Cartesian trajectory is modified to a circular trajectory in 2D and a cylindrical trajectory in 3D for reduced echo train time. Incorporation of "fly-back" trajectories lengthened the time of the subsequences and proportionally increased susceptibility artifact but the unipolar readout gradients eliminate all ghost artifacts. The modified cylindrical trajectory reduced susceptibility artifact and distortion artifact while raising the signal-to-noise ratio in both phantom and human brain images.

Facial appearance is a cue to oestrogen levels in women.

Although many accounts of facial attractiveness propose that femininity in women's faces indicates high levels of oestrogen, there is little empirical evidence in support of this assumption. Here, we used assays for urinary metabolites of oestrogen (oestrone-3-glucuronide, E1G) and progesterone (pregnanediol-3-glucuronide, P3G) to investigate the relationship between circulating gonadal hormones and ratings of the femininity, attractiveness and apparent health of women's faces. Positive correlations were observed between late follicular oestrogen and ratings of femininity, attractiveness and health. Positive correlations of luteal progesterone and health and attractiveness ratings were marginally significant. Ratings of facial attributions did not relate to hormone levels for women wearing make-up when photographed. There was no effect of sex of rater on the relationships between oestrogen and ratings of facial appearance. These findings demonstrate that female facial appearance holds detectable cues to reproductive health that are considered attractive by other people.

Menstrual cycle, pregnancy and oral contraceptive use alter attraction to apparent health in faces.

Previous studies demonstrating changes in women's face preferences have emphasized increased attraction to cues to possible indirect benefits (e.g. heritable immunity to infection) that coincides with periods of high fertility (e.g. the late follicular phase of the menstrual cycle). By contrast, here we show that when choosing between composite faces with raised or lowered apparent health, women's preferences for faces that are perceived as healthy are (i) stronger during the luteal phase of the menstrual cycle than during the late follicular, fertile phase, (ii) stronger in pregnant women than in non-pregnant women and (iii) stronger in women using oral contraceptives than in women with natural menstrual cycles. Change in preference for male faces was greater for short- than long-term relationships. These findings indicate raised progesterone level is associated with increased attraction to facial cues associated with possible direct benefits (e.g. low risk of infection) and suggest that women's face preferences are influenced by adaptations that compensate for weakened immune system responses during pregnancy and reduce the risk of infection disrupting foetal development.

Parameterization of the shape of intracranial saccular aneurysms using Legendre polynomials.

Our recent studies of the nonlinear mechanics of saccular aneurysms suggest that it is unlikely that these lesions enlarge or rupture via material (limit point) or dynamic (resonance) instabilities. Rather, there is a growing body of evidence from both vascular biology and biomechanical analyses that implicate mechanosensitive growth and remodeling processes. There is, therefore, a pressing need to quantify regional multiaxial wall stresses which, because of the membrane-like behavior of many aneurysms, necessitates better information on the applied loads and regional surface curvatures. Herein, we present and illustrate a method whereby regional curvatures can be estimated easily for sub-classes of human aneurysms based on clinically available data from magnetic resonance angiography (MRA). Whereas Legendre polynomials are used to illustrate this approach, different functions may prove useful for different sub-classes of lesions.

Distinct light microscopic changes in human immunodeficiency virus-associated nemaline myopathy.

The purpose of this study was to compare histologic characteristics of congenital nemaline myopathy (CNM), adult-onset nemaline myopathy (AONM), and human immunodeficiency virus-associated adult-onset nemaline myopathy (HAONM). There was no difference between the pathology of CNM and AONM; however, HAONM had distinctive pathologic features by light microscopy. The fibers in HAONM showed marked intrasarcoplasmic changes, including small vacuoles and granular degeneration.

Postural change of forced vital capacity predicts some respiratory symptoms in ALS.

The detection of respiratory muscle weakness in ALS is necessary to plan initiation of noninvasive positive pressure ventilation and begin discussion of advanced directives. The authors measured the erect seated and supine forced vital capacity (FVC) in 38 patients with ALS and 15 controls. The supine FVC is significantly lower and the erect--supine FVC difference is significantly greater in patients with complaints of dyspnea, orthopnea, and daytime fatigue.

Changes in size and magnetic resonance signal intensity of the cerebral CSF spaces during the cardiac cycle as studied by gated, high-resolution magnetic resonance imaging.

In 1966, du Boulay demonstrated the pulsatile nature of CSF flow in the cerebral aqueduct by using air cineventriculography, which disturbs normal CSF dynamics by replacing part of the incompressible CSF with air. To investigate this phenomenon noninvasively, 35 normal volunteers were studied using high-resolution, cardiac-gated MR imaging. Specifically, we wished to document changes in size and configuration of the CSF spaces and the incidence and magnitude of signal loss (an indication of CSF motion) in these spaces as they related to time in the cardiac cycle. Changes in size and configuration were measurable in the third ventricle only (size increased during systole in seven of the 35 volunteers). Except for the lateral ventricles, some loss in signal intensity was seen in all CSF spaces at least during systole in all 35 volunteers--findings consistent with those of du Boulay. However, contrary to du Boulay's observations, asymmetric loss of signal, consistent with pulsatile CSF flow, was demonstrated at the level of the foramen of Monro in 15 of the 35 volunteers. Based on the pattern of flow void at the level of the foramen of Monro and on the expansion of the third ventricle during systole, we propose a theory of synchronous CSF flow at the foramen of Monro and aqueduct, which unifies our MR findings with du Boulay's cineventriculographic observations.

Parent-assisted transfer of children's social skills training: effects on children with and without attention-deficit hyperactivity disorder.

OBJECTIVE: Previous research has demonstrated that peer rejection is a significant part of the clinical presentation of many children with attention-deficit hyperactivity disorder (ADHD). Outcome studies of treatment interventions have typically failed to show generalization of treatment gains to the home and classroom. This has been especially true for children who have comorbid oppositional defiant disorder (ODD). The present study was intended to demonstrate generalization of an outpatient social skills training program when parents were trained in skills relevant to their child's social adjustment. METHOD: Thirty-five children with ADHD and 14 children without ADHD were given 12 sessions of treatment (treatment group). Outcome was compared with 12 children with ADHD and 12 children without ADHD who were on a waitlist for treatment (waitlist group). Nineteen children with ODD were in the treatment group and five in the waitlist. Stimulant medication was prescribed for all children with ADHD. RESULTS: Subjects with ADHD showed improvement comparable with that of subjects without ADHD on all teacher- and parent-reported measures of peer adjustment and social skills, except teacher-reported withdrawal. Children with ODD had outcome comparable with that of children without ODD. Effect sized ranged from 0.93 to 1.34 indicating that the average treatment group subject was better off than 83.4% of waitlist subjects on outcome measures. CONCLUSIONS: The present results suggest that children with ADHD are best heiped by a combination of social skills training for themselves, collateral training for their parents and stimulant medication.

Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial.

OBJECTIVE: To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression. METHOD: After a 7- to 14-day screening period, 275 adolescents with major depression began 8 weeks of double-blind paroxetine (20-40 mg), imipramine (gradual upward titration to 200-300 mg), or placebo. The two primary outcome measures were endpoint response (Hamilton Rating Scale for Depression [HAM-D] score < or = 8 or > or = 50% reduction in baseline HAM-D) and change from baseline HAM-D score. Other depression-related variables were (1) HAM-D depressed mood item; (2) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version (K-SADS-L); (3) Clinical Global Impression (CGI) improvement scores of 1 or 2; (4) nine-item depression subscale of K-SADS-L; and (5) mean CGI improvement scores. RESULTS: Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score < or = 8, HAM-D depressed mood item, K-SADS-L depressed mood item, and CGI score of 1 or 2. The response to imipramine was not significantly different from placebo for any measure. Neither paroxetine nor imipramine differed significantly from placebo on parent- or self-rating measures. Withdrawal rates for adverse effects were 9.7% and 6.9% for paroxetine and placebo, respectively. Of 31.5% of subjects stopping imipramine therapy because of adverse effects, nearly one third did so because of adverse cardiovascular effects. CONCLUSIONS: Paroxetine is generally well tolerated and effective for major depression in adolescents.

Do stimulants improve self-esteem in children with ADHD and peer problems?

The self-esteem of children with Attention Deficit Hyperactivity Disorder (ADHD) has been shown to be low. The effects of stimulant medication upon their self-esteem have not been systematically studied. The present study employed a reliable self-report instrument to measure the self-esteem of children with ADHD medicated with stimulants vs. those who were unmedicated. Results showed that stimulants were associated with significantly higher self-esteem. Children with ADHD prescribed stimulants reported feeling more intelligent and more popular than unmedicated children with ADHD. Children with ADHD and Oppositional Defiant Disorder (ODD) prescribed stimulants reported feeling better behaved. Significant correlations indicated that higher doses were associated with higher self-esteem. The present results suggest a need for a well-controlled study to determine if stimulants were responsible for the observed differences in self-esteem.

Functional magnetic resonance imaging. Application to degenerative brain disease and hydrocephalus.

Magnetic resonance (MR) imaging, in addition to its excellent depiction of neuroanatomy, is being developed as a major technique for functional imaging of cerebrospinal fluid motion and for measurement of velocity, strain, and diffusional processes within the brain parenchyma. Functional MR imaging studies are revealing basic physiology of blood flow interactions with CSF motion and dynamic processes of brain parenchyma. Normal pressure hydrocephalus and degenerative brain disease are current focuses of functional MR imaging studies.

Use of the Child Behavior Checklist and DSM-III-R diagnosis in predicting outcome of children's social skills training.

A standardized 12-week cognitive-behavioral social skills package in which parents assisted children with socialization homework assignments, was presented to 52 nonpsychotic outpatient boys, many of whom were diagnosed with DSM-III-R Attention Deficit-Hyperactivity Disorder and Oppositional Defiant Disorder. Results demonstrated that the Thought Problems factor of the mother-completed Child Behavior Checklist aided in predicting changes in teacher-rated aggression. DSM-III-R diagnosis of Oppositional Defiant Disorder predicted changes in teacher-rated withdrawal subsequent to treatment. The need for research to determine which children benefit from which treatment was discussed.