Caitlin K. Rollins

Copy number variation plays an important role in clinical epilepsy

To evaluate the role of copy number abnormalities detectable using chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center.

White matter microstructure and cognition in adolescents with congenital heart disease.

OBJECTIVE To describe the relationship between altered white matter microstructure and neurodevelopment in children with dextro-transposition of the great arteries (d-TGA). STUDY DESIGN We report correlations between regional white matter microstructure as measured by fractional anisotropy (FA) and cognitive outcome in a homogeneous group of adolescents with d-TGA. Subjects with d-TGA (n = 49) and controls (n = 29) underwent diffusion tensor imaging and neurocognitive testing. In the group with d-TGA, we correlated neurocognitive scores with FA in 14 composite regions of interest in which subjects with d-TGA had lower FA than controls. RESULTS Among the patients with d-TGA, mathematics achievement correlated with left parietal FA (r = 0.39; P = .006), inattention/hyperactivity symptoms correlated with right precentral FA (r = -0.39; P = .006) and left parietal FA (r = -0.30; P = .04), executive function correlated with right precentral FA (r = -0.30; P = .04), and visual-spatial skills correlated with right frontal FA (r = 0.30; P = .04). We also found an unanticipated correlation between memory and right posterior limb of the internal capsule FA (r = 0.29; P = .047). CONCLUSION Within the group with d-TGA, regions of reduced white matter microstructure are associated with cognitive performance in a pattern similar to that seen in healthy adolescents and adults. Diminished white matter microstructure may contribute to cognitive compromise in adolescents who underwent open-heart surgery in infancy.

Risk-adjusting outcomes of mental health and substance-related care: a review of the literature.

Risk adjustment is increasingly recognized as crucial to refining health care reimbursement and to comparing provider performance in terms of quality and outcomes of care. Risk adjustment for mental and substance use conditions has lagged behind other areas of medicine, but model development specific to these conditions has accelerated in recent years. After describing outcomes of mental health and substance-related care and associated risk factors, we review research studies on risk adjustment meeting the following criteria: (1) publication in a peer-reviewed journal between 1980 and 2002, (2) evaluation of one or more multivariate models used to risk-adjust comparisons of utilization, cost, or clinical outcomes of mental or substance use conditions across providers, and (3) quantitative assessment of the proportion of variance explained by patient characteristics in the model (e.g., R(2) or c-statistic). We identified 36 articles that included 72 models addressing utilization, 74 models of expenditures, and 15 models of clinical outcomes. Models based on diagnostic and sociodemographic information available from administrative data sets explained an average 6.7% of variance, whereas models using more detailed sources of data explained a more robust 22.8%. Results are appraised in the context of the mental health care systems needs for risk adjustment; we assess what has been accomplished, where gaps remain, and directions for future development.

A normative spatiotemporal MRI atlas of the fetal brain for automatic segmentation and analysis of early brain growth

Longitudinal characterization of early brain growth in-utero has been limited by a number of challenges in fetal imaging, the rapid change in size, shape and volume of the developing brain, and the consequent lack of suitable algorithms for fetal brain image analysis. There is a need for an improved digital brain atlas of the spatiotemporal maturation of the fetal brain extending over the key developmental periods. We have developed an algorithm for construction of an unbiased four-dimensional atlas of the developing fetal brain by integrating symmetric diffeomorphic deformable registration in space with kernel regression in age. We applied this new algorithm to construct a spatiotemporal atlas from MRI of 81 normal fetuses scanned between 19 and 39 weeks of gestation and labeled the structures of the developing brain. We evaluated the use of this atlas and additional individual fetal brain MRI atlases for completely automatic multi-atlas segmentation of fetal brain MRI. The atlas is available online as a reference for anatomy and for registration and segmentation, to aid in connectivity analysis, and for groupwise and longitudinal analysis of early brain growth.

Temporal slice registration and robust diffusion-tensor reconstruction for improved fetal brain structural connectivity analysis

&NA; Diffusion weighted magnetic resonance imaging, or DWI, is one of the most promising tools for the analysis of neural microstructure and the structural connectome of the human brain. The application of DWI to map early development of the human connectome in‐utero, however, is challenged by intermittent fetal and maternal motion that disrupts the spatial correspondence of data acquired in the relatively long DWI acquisitions. Fetuses move continuously during DWI scans. Reliable and accurate analysis of the fetal brain structural connectome requires careful compensation of motion effects and robust reconstruction to avoid introducing bias based on the degree of fetal motion. In this paper we introduce a novel robust algorithm to reconstruct in‐vivo diffusion‐tensor MRI (DTI) of the moving fetal brain and show its effect on structural connectivity analysis. The proposed algorithm involves multiple steps of image registration incorporating a dynamic registration‐based motion tracking algorithm to restore the spatial correspondence of DWI data at the slice level and reconstruct DTI of the fetal brain in the standard (atlas) coordinate space. A weighted linear least squares approach is adapted to remove the effect of intra‐slice motion and reconstruct DTI from motion‐corrected data. The proposed algorithm was tested on data obtained from 21 healthy fetuses scanned in‐utero at 22–38 weeks gestation. Significantly higher fractional anisotropy values in fiber‐rich regions, and the analysis of whole‐brain tractography and group structural connectivity, showed the efficacy of the proposed method compared to the analyses based on original data and previously proposed methods. The results of this study show that slice‐level motion correction and robust reconstruction is necessary for reliable in‐vivo structural connectivity analysis of the fetal brain. Connectivity analysis based on graph theoretic measures show high degree of modularity and clustering, and short average characteristic path lengths indicative of small‐worldness property of the fetal brain network. These findings comply with previous findings in newborns and a recent study on fetuses. The proposed algorithm can provide valuable information from DWI of the fetal brain not available in the assessment of the original 2D slices and may be used to more reliably study the developing fetal brain connectome.

White Matter Volume Predicts Language Development in Congenital Heart Disease

Objective To determine whether brain volume is reduced at 1 year of age and whether these volumes are associated with neurodevelopment in biventricular congenital heart disease (CHD) repaired in infancy. Study design Infants with biventricular CHD (n = 48) underwent brain magnetic resonance imaging (MRI) and neurodevelopmental testing with the Bayley Scales of Infant Development‐II and the MacArthur‐Bates Communicative Development Inventories at 1 year of age. A multitemplate based probabilistic segmentation algorithm was applied to volumetric MRI data. We compared volumes with those of 13 healthy control infants of comparable ages. In the group with CHD, we measured Spearman correlations between neurodevelopmental outcomes and the residuals from linear regression of the volumes on corrected chronological age at MRI and sex. Results Compared with controls, infants with CHD had reductions of 54 mL in total brain (P = .009), 40 mL in cerebral white matter (P < .001), and 1.2 mL in brainstem (P = .003) volumes. Within the group with CHD, brain volumes were not correlated with Bayley Scales of Infant Development‐II scores but did correlate positively with MacArthur‐Bates Communicative Development Inventory language development. Conclusions Infants with biventricular CHD show total brain volume reductions at 1 year of age, driven by differences in cerebral white matter. White matter volume correlates with language development, but not broader developmental indices. These findings suggest that abnormalities in white matter development detected months after corrective heart surgery may contribute to language impairment. Trial registration ClinicalTrials.gov: NCT00006183.

Quality measurement in health care: A need for leadership amid a new federalism

Over the past decade, market forces have increasingly reshaped the American health care system. Public and private payers have hired for-profit managed care organizations to approve the utilization of health care services. Purchasers and their employees select among competing health plans. Health care facilities and systems vie for contracts to treat populations of patients. The infusion of market forces into the health care system has outpaced the dissemination of data on the quality of care. Market forces can allocate resources efficiently in the presence of what economists term “perfect information.” But in the health care marketplace, not even imperfect information is available. While employees may receive information about health care benefits to guide their choices among plans, they know little about the intensity and types of care allowed by a plan’s utilization-review criteria. Similarly, consumers, purchasers, and payers lack sufficient information to compare providers based on their quality of the care. Market economics suggest that when purchasers lack information that differentiates products on the basis of quality, they will maximize their utility by seeking the lowest price. If providers and plans are unable to demonstrate higher quality, they will have little financial incentive to expend resources to improve care. In fact, greater resource utiliza-

Neurodevelopmental Outcomes in Congenital Heart Disease

As improved treatments for congenital heart disease (CHD) have increased life expectancy, neurodevelopmental impairments have been observed in many survivors. These impairments include developmental delays, difficulty in school, and challenges living independently. Understanding the causes of these impairments and minimizing their impact are important goals to allow survivors to have the best possible quality of life. CHD may affect the brain in several ways. First, the heart pumps blood that carries nutrients and oxygen to the brain to allow it to grow and develop. Some types of CHD may reduce the amount of blood reaching the brain or the oxygen content of the blood. Starting in the fetal period, reduced blood flow and oxygen content may impede brain maturation. Indeed, full-term babies with some types of heart defects have brain maturity that is about 1 month delayed (ie, similar to those of premature babies born at 36 weeks).1 Brain injury may also occur in CHD. Brain immaturity increases the risk of brain injury with stresses such as labor and delivery, blood pressure instability, or infection. White matter, a tissue connecting different regions of the brain, is particularly vulnerable to injury. White matter injury …

Quantitative Folding Pattern Analysis of Early Primary Sulci in Human Fetuses with Brain Abnormalities

BACKGROUND AND PURPOSE: Aberrant gyral folding is a key feature in the diagnosis of many cerebral malformations. However, in fetal life, it is particularly challenging to confidently diagnose aberrant folding because of the rapid spatiotemporal changes of gyral development. Currently, there is no resource to measure how an individual fetal brain compares with normal spatiotemporal variations. In this study, we assessed the potential for automatic analysis of early sulcal patterns to detect individual fetal brains with cerebral abnormalities. MATERIALS AND METHODS: Triplane MR images were aligned to create a motion-corrected volume for each individual fetal brain, and cortical plate surfaces were extracted. Sulcal basins were automatically identified on the cortical plate surface and compared with a combined set generated from 9 normal fetal brain templates. Sulcal pattern similarities to the templates were quantified by using multivariate geometric features and intersulcal relationships for 14 normal fetal brains and 5 fetal brains that were proved to be abnormal on postnatal MR imaging. Results were compared with the gyrification index. RESULTS: Significantly reduced sulcal pattern similarities to normal templates were found in all abnormal individual fetuses compared with normal fetuses (mean similarity [normal, abnormal], left: 0.818, 0.752; P < .001; right: 0.810, 0.753; P < .01). Altered location and depth patterns of sulcal basins were the primary distinguishing features. The gyrification index was not significantly different between the normal and abnormal groups. CONCLUSIONS: Automated analysis of interrelated patterning of early primary sulci could outperform the traditional gyrification index and has the potential to quantitatively detect individual fetuses with emerging abnormal sulcal patterns.

Disorganized Patterns of Sulcal Position in Fetal Brains with Agenesis of Corpus Callosum

Fetuses with isolated agenesis of the corpus callosum (ACC) are associated with a broad spectrum of neurodevelopmental disability that cannot be specifically predicted in prenatal neuroimaging. We hypothesized that ACC may be associated with aberrant cortical folding. In this study, we determined altered patterning of early primary sulci development in fetuses with isolated ACC using novel quantitative sulcal pattern analysis which measures deviations of regional sulcal features (position, depth, and area) and their intersulcal relationships in 7 fetuses with isolated ACC (27.1 ± 3.8 weeks of gestation, mean ± SD) and 17 typically developing (TD) fetuses (25.7 ± 2.0 weeks) from normal templates. Fetuses with ACC showed significant alterations in absolute sulcal positions and relative intersulcal positional relationship compared to TD fetuses, which were not detected by traditional gyrification index. Our results reveal altered sulcal positional development even in isolated ACC that is present as early as the second trimester and continues throughout the fetal period. It might originate from altered white matter connections and portend functional variances in later life.