Early Antiretroviral Therapy in HIV-Infected Children Is Associated with Diffuse White Matter Structural Abnormality and Corpus Callosum Sparing.

BACKGROUND AND PURPOSE: Fractional anisotropy in the frontal white matter, corpus callosum, and internal capsule is abnormal in human immunodeficiency virus-positive (HIV+) adults. We describe the distribution and nature of white matter abnormalities in a cohort of children who started antiretroviral therapy within the first year of life and the benefit of early treatment by using DTI measures (fractional anisotropy and mean, axial, and radial diffusion). MATERIALS AND METHODS: DTI was performed on children in a neurodevelopmental substudy from the Children with HIV Early Antiretroviral trial. Voxel-based group comparisons were obtained to determine regions where fractional anisotropy and mean diffusion differed between HIV+ and uninfected children. Associations of DTI parameters with the timing of antiretroviral therapy initiation were examined. RESULTS: Thirty-nine HIV+ children (15 boys; mean age, 5.4 years) and 13 controls (5 boys; mean age, 5.7 years) were scanned. Two clusters with lower fractional anisotropy and 7 clusters with increased mean diffusion were identified in the HIV+ group, with symmetric distribution predominantly due to increased radial diffusion, suggestive of decreased myelination. Corticospinal tracts rather than the corpus callosum were predominantly involved. Children on early-interrupted antiretroviral therapy had lower fractional anisotropy compared with those receiving continuous treatment. CONCLUSIONS: HIV+ children at 5 years of age have white matter abnormalities measured by fractional anisotropy, despite early antiretroviral therapy, suggesting that early antiretroviral therapy does not fully protect the white matter from either peripartum or in utero infection. In contrast to adults, the corticospinal tracts are predominantly involved rather than the corpus callosum, possibly due to early antiretroviral therapy. Continuous early antiretroviral therapy can limit white matter damage.

Parietal dysfunction during number processing in children with fetal alcohol spectrum disorders.

Number processing deficits are frequently seen in children prenatally exposed to alcohol. Although the parietal lobe, which is known to mediate several key aspects of number processing, has been shown to be structurally impaired in fetal alcohol spectrum disorders (FASD), effects on functional activity in this region during number processing have not previously been investigated. This fMRI study of 49 children examined differences in activation associated with prenatal alcohol exposure in five key parietal regions involved in number processing, using tasks involving simple addition and magnitude comparison. Despite generally similar behavioral performance, in both tasks greater prenatal alcohol exposure was related to less activation in an anterior section of the right horizontal intraparietal sulcus known to mediate mental representation and manipulation of quantity. Children with fetal alcohol syndrome and partial fetal alcohol syndrome appeared to compensate for this deficit by increased activation of the angular gyrus during the magnitude comparison task.

A tensor-based morphometry analysis of regional differences in brain volume in relation to prenatal alcohol exposure.

Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD). Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM) methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6-11.0 years) and controls (n = 16, 9.5-11.0 years). Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1) the thalamus, midbrain, and ventromedial frontal lobe, (2) the superior cerebellum and inferior occipital lobe, (3) the dorsolateral frontal cortex, and (4) the precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA) regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent.

Motion artifact removal for functional near infrared spectroscopy: a comparison of methods.

Near infrared spectroscopy (NIRS) is rapidly gaining popularity for functional brain imaging. It is well suited to studies of patients or children; however, in these populations particularly, motion artifacts can present a problem. Here, we propose the use of imaging channels with negligible distance between light source and detector to detect subject motion, without the need for an additional motion sensor. Datasets containing deliberate motion artifacts were obtained from three subjects. Motion artifacts could be detected in the signal from the co-located channels with a minimum sensitivity of 0.75 and specificity of 0.98. Five techniques for removing motion artifact from the functional signals were compared, namely two-input recursive least squares (RLS) adaptive filtering, wavelet-based filtering, independent component analysis (ICA), and two-channel and multiple-channel regression. In most datasets, the median change in SNR across all channels was the greatest using ICA or multiple-channel regression. RLS adaptive filtering produced the smallest increase in SNR. Where sharp spikes were present, wavelet filtering produced the largest SNR increase. ICA and multiple-channel regression are promising ways to reduce motion artifact in functional NIRS without requiring time-consuming manual techniques.

Abnormal diastolic and systolic septal motion following pericardiectomy demonstrated by ciné DENSE MRI.

Constrictive pericarditis can lead to paradoxical interventricular septal motion. Displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) provides a method for quantifying myocardial motion and strain. A case of constrictive pericarditis is presented and the diastolic 'septal bounce' is clearly evident in both anatomical and DENSE ciné MRI images. (See video link to full-text electronic article). The postoperative systolic septal wall-motion abnormality of cardiac surgery is portrayed with greater precision by DENSE than anatomical ciné MRI images.

Tracking myocardial motion from cine DENSE images using spatiotemporal phase unwrapping and temporal fitting.

Displacement encoding with stimulated echoes (DENSE) encodes myocardial tissue displacement into the phase of the MR image. Cine DENSE allows for rapid quantification of myocardial displacement at multiple cardiac phases through the majority of the cardiac cycle. For practical sensitivities to motion, relatively high displacement encoding frequencies are used and phase wrapping typically occurs. In order to obtain absolute measures of displacement, a two-dimensional (2-D) quality-guided phase unwrapping algorithm was adapted to unwrap both spatially and temporally. Both a fully automated algorithm and a faster semi-automated algorithm are proposed. A method for computing the 2-D trajectories of discrete points in the myocardium as they move through the cardiac cycle is introduced. The error in individual displacement measurements is reduced by fitting a time series to sequential displacement measurements along each trajectory. This improvement is in turn reflected in strain maps, which are derived directly from the trajectories. These methods were validated both in vivo and on a rotating phantom. Further measurements were made to optimize the displacement encoding frequency and to estimate the baseline strain noise both on the phantom and in vivo. The fully automated phase unwrapping algorithm was successful for 767 out of 800 images (95.9%), and the semi-automated algorithm was successful for 786 out of 800 images (98.3%). The accuracy of the tracking algorithm for typical cardiac displacements on a rotating phantom is 0.24 +/- 0.15 mm. The optimal displacement encoding frequency is in the region of 0.1 cycles/mm, and, for 2 scans of 17-s duration, the strain noise after temporal fitting was estimated to be 2.5 +/- 3.0% at end-diastole, 3.1 +/- 3.1% at end-systole, and 5.3 +/- 5.0% in mid-diastole. The improvement in intra-myocardial strain measurements due to temporal fitting is apparent in strain histograms, and also in identifying regions of dysfunctional myocardium in studies of patients with infarcts.

Eye feature extraction for diagnosing the facial phenotype associated with fetal alcohol syndrome.

Victims of fetal alcohol syndrome (FAS) exhibit a unique facial phenotype that is emphasised in diagnosis. Among the characteristic facial features, several occurring in the region of the orbits can be evaluated quantitatively using distance measurements. An algorithm is described for automatic extraction and measurement of eye features from stereo photographs. The algorithm was applied to photographs of 46 six-seven-year-old children. The approach relies on peak and valley maps and integral projection functions, to locate the eyes and extract the iris, and genetic algorithms to fit cubic splines to the upper and lower eyelids. Measurements obtained automatically using this algorithm were compared with measurements obtained manually from the photographs. Mean absolute differences between automatic and manual measurements were less than 1 mm for palpebral fissure length (PFL) and interpupillary distance (IPD). Absolute differences were less than 1 mm for 80.4% of PFLs and 100% of IPDs. Inner canthal distance and outer canthal distance did not compare favourably with manual measurements.

A stereo-photogrammetric method to measure the facial dysmorphology of children in the diagnosis of fetal alcohol syndrome.

In diagnosing a child with fetal alcohol syndrome (FAS), anthropometric measurements of the face are conventionally performed by highly trained dysmorphologists using a hand-held ruler. This renders the screening of large populations of children for the facial features characteristic of FAS very time-consuming and costly. This study proposes a new, cost-effective, and non-intrusive method to measure in three dimensions the facial dysmorphology of children using stereo-photogrammetry. The face of each child is photographed in a control frame simultaneously by a pair of high-resolution digital cameras mounted 1.04 m from the child and 0.26 m apart. Software has been developed to calibrate the images and to compute the three-dimensional object-space coordinates of any point on the face from a measurement of the point on each of the images. The palpebral fissure lengths, inner canthal-, and interpupillary distances of 44 subjects were measured in this manner independently by two investigators and compared with measurements obtained by clinical specialists in the conventional manner. There was found to be no statistically significant difference between palpebral fissure lengths determined using the two techniques (paired Student's t-test p-values are 0.29 and 0.18, respectively). It has also been demonstrated that facial measurements can be performed with greater consistency from a pair of stereo photographs than direct measurements from live subjects.