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Biomedical subjects

Steven P Miller

Publications and source records attributed to Steven P Miller.

29 records · Page 2Linked to original sources

Diffusion tensor imaging: serial quantitation of white matter tract maturity in premature newborns.

Magnetic resonance diffusion tensor imaging (DTI) enables the discrimination of white matter pathways before myelination is evident histologically or on conventional MRI. In this investigation, 14 premature neonates with no evidence of white matter abnormalities by conventional MRI were studied with DTI. A custom MR-compatible incubator with a novel high sensitivity neonatal head coil and improved acquisition and processing techniques were employed to increase image quality and spatial resolution. The technical improvements enabled tract-specific quantitative characterization of maturing white matter, including several association tracts and subcortical projection tracts not previously investigated in neonates by MR. Significant differences were identified between white matter pathways, with earlier maturing commissural tracts of the corpus callosum, and deep projection tracts of the cerebral peduncle and internal capsule exhibiting lower mean diffusivity (Dav) and higher fractional anisotropy (FA) than later maturing subcortical projection and association pathways. Maturational changes in white matter tracts included reductions in Dav and increases in FA with age due primarily to decreases in the two minor diffusion eigenvalues (lambda2 and lambda3). This work contributes to the understanding of normal white matter development in the preterm neonatal brain, an important step toward the use of DTI for the improved evaluation and treatment of white matter injury of prematurity.

Anisotropy↗

Clinical signs predict 30-month neurodevelopmental outcome after neonatal encephalopathy.

OBJECTIVE: This study was undertaken to determine the value of a neonatal encephalopathy score (ES) and the presence of seizures for predicting 30-month neurodevelopmental outcome. STUDY DESIGN: In a cohort study, 68 term newborn infants with encephalopathy were evaluated with an ES based on alertness, feeding, tone, respiratory status, reflexes, and seizure activity (range: 0-6). Seizures were noted as present or absent clinically. Significant cognitive deficits (Mental Development Index <70), motor disability (spastic triplegia/quadriplegia), or death were abnormal outcomes. RESULTS: Twenty-two newborn infants (32%) had abnormal outcomes. With the use of maximum ES and presence of seizures from days 1 to 3 of life, 87% of newborn infants were correctly classified (area under receiver operating curve 0.93). By using ES and presence of seizures on day 1 only, 87% of newborn infants were correctly classified (area under receiver operating curve 0.89). CONCLUSION: The severity of neonatal encephalopathy and the presence of seizures are valuable predictors of 30-month neurodevelopmental outcome, as early as the first day of life.

Aging↗

Rhodium-catalyzed enantioselective diboration of simple alkenes.

Enantioselective catalytic reactions that operate directly on inexpensive unactivated alkenes are extraordinarily useful for the preparation of chiral organic building blocks and new materials. While a number of such processes have been developed, our ability to meet the intensifying demand for inexpensive stereochemically complex materials will require a significant expansion of practical catalytic asymmetric reaction methodology. In this regard, the rhodium-catalyzed enantioselective diboration reaction has been developed in order to address a number of extant problems in catalytic alkene transformation simultaneously. This process provides an enantiomerically enriched reactive dimetalated intermediate which can be converted to a variety of difunctional reaction products.

Alcohols↗

Intraventricular hemorrhage in term neonates caused by sinovenous thrombosis.

The cause of intraventricular hemorrhage in term neonates is poorly understood. Among 29 neonates of at least 36 weeks' gestation with intraventricular hemorrhage, 9 (31%) had cerebral sinovenous thrombosis. Of the 26 neonates who underwent computed tomography or magnetic resonance studies, those with thalamic hemorrhage were more likely to have sinovenous thrombosis than those without thalamic involvement (4/5 vs 5/21, p = 0.03). Term neonates with intraventricular hemorrhage should undergo neuroimaging to evaluate the presence of sinovenous thrombosis. Ann Neurol 2003

Cerebral Hemorrhage↗

DTI-based three-dimensional tractography detects differences in the pyramidal tracts of infants and children with congenital hemiparesis.

PURPOSE: To test the hypothesis that there is greater asymmetry in diffusion properties between right and left pyramidal tracts in patients with congenital hemiparesis than in patients with normal motor function. MATERIALS AND METHODS: Four congenitally hemiparetic patients and four age-matched controls underwent magnetic resonance diffusion tensor imaging (DTI)-based three-dimensional tractography of the pyramidal tracts. Relative anisotropy, individual eigenvalues, and directionally averaged apparent diffusion coefficient were measured and degree of asymmetry was calculated. RESULTS: Compared with age-matched controls, congenitally hemiparetic patients had greater asymmetry in all measured diffusion properties. The asymmetry was characterized primarily by lower anisotropy, lower parallel diffusion, higher transverse diffusion, and slightly higher mean diffusivity in the pyramidal tract contralateral to the hemiparesis (i.e., affected pyramidal tract) compared with the unaffected pyramidal tract. CONCLUSIONS: There appears to be greater diffusion asymmetry between the pyramidal tracts in congenitally hemiparetic patients compared to controls. These differences suggest that there are alterations in the microstructure of the pyramidal tract that controls the motor function of the hemiparetic side. Our results suggest that DTI-based three-dimensional tractography is potentially useful in the assessment of motor dysfunction in infants and children with congenital hemiparesis.

Anisotropy↗

Encephalopathy as a predictor of magnetic resonance imaging abnormalities in asphyxiated newborns.

Basal ganglia abnormalities on magnetic resonance imaging predict neurodevelopmental impairment in newborns with perinatal depression. We determined the value of a clinical encephalopathy score as a predictor of abnormal magnetic resonance imaging results in newborns with perinatal depression. We assigned a neonatal encephalopathy score to 101 newborns. The encephalopathy score, based on alertness, feeding, tone, respiratory status, reflexes, and seizure activity, was assigned once daily. The maximum score from the first 3 days of life was compared with abnormal magnetic resonance imaging results present globally or solely in the basal ganglia.Eighty-one percent of patients manifested abnormalities on any magnetic resonance imaging sequence, and 37% manifested abnormalities in the basal ganglia alone. The encephalopathy score correlated well with magnetic resonance imaging abnormalities in the basal ganglia (Spearman Rho = 0.335, P < 0.0001). Newborns with mild and severe encephalopathy had likelihood ratios of 0.41 and 7.4, respectively, for abnormal basal ganglia magnetic resonance imaging results. Newborns with moderate encephalopathy (composing 47% of the cohort) manifested basal ganglia abnormalities with a likelihood ratio of 0.785. Severe clinical encephalopathy correlates with abnormal basal ganglia magnetic resonance imaging results, and mild encephalopathy correlates with a normal magnetic resonance imaging result. However, standard clinical criteria do not alter the prior risk of abnormal basal ganglia magnetic resonance imaging results for newborns with moderate encephalopathy.

Asphyxia Neonatorum↗

Nucleated red blood cell counts: not associated with brain injury or outcome.

The objective was to determine whether an elevated nucleated red blood cell count at birth after perinatal depression is associated with brain injury as measured by (1) proton magnetic resonance spectroscopy and (2) abnormal neurodevelopmental outcome at 30 months of age. The nucleated red blood cell counts from the first 24 hours of life were statistically analyzed in 33 term infants enrolled in a prospective study of the value of magnetic resonance imaging for the determination of neurodevelopmental outcome after perinatal depression. Nucleated red blood cell counts were elevated in 13/33 (39%). Abnormal outcome (19/33, 54%) was associated with Score for Neonatal Acute Physiology-Perinatal Extension (P = 0.04), decreased N-acetylaspartate to choline ratio in the basal ganglia (P = 0.009), and increased lactate to choline ratio in the basal ganglia (P = 0.02), but not with cord pH, Apgar score, or nucleated red blood cell value. In a logistic regression model, increasing nucleated red blood cell counts did not increase the odds of an abnormal outcome at 30 months of age (OR 1.02, P = 0.17). In a population of neonates with perinatal depression, the nucleated red blood cell count at birth does not correlate with magnetic resonance spectroscopy or 30-month neurodevelopmental outcome. The nucleated red blood cell count should not be used as a surrogate marker for subsequent brain injury.

Brain Injuries↗

Comparing the diagnosis of white matter injury in premature newborns with serial MR imaging and transfontanel ultrasonography findings.

BACKGROUND AND PURPOSE: The accurate identification of white matter injury in premature neonates is important for counseling parents and for targeting these high risk neonates for appropriate rehabilitation services. The objective of this study was to compare the diagnosis of white matter injury detected by serial MR imaging and ultrasonography of a contemporary cohort of premature neonates. METHODS: Each of the 32 consecutively enrolled neonates was studied with MR imaging at a median postconceptional age of 31.9 weeks (range, 27.6-38.1 weeks) and again at a median postconceptional age of 36.5 weeks (range, 33.4-42.9 weeks) and with serial ultrasonography according to a clinical protocol. Because periventricular echogenicity shown on ultrasonograms evolves over time, both the highest grade of echogenicity and the grade of echogenicity shown on the last neonatal ultrasonogram were used in the analysis to determine the predictive values and correlation (Spearman's rho) of ultrasonography for predicting white matter abnormalities shown on MR images. RESULTS: White matter abnormalities were diagnosed in 18 (56%) neonates based on MR imaging, consisting of foci of scattered T1 hyperintensity in the periventricular white matter, and in 22 (69%) neonates based on ultrasonography, consisting of abnormal periventricular echogenicity. The severity of white matter abnormalities shown by MR imaging was not correlated with the highest grade of white matter abnormalities detected with ultrasonography (rho=0.18, P=.3) or with the grade of white matter abnormalities shown on the last ultrasonogram (rho = 0.16, P=.4). CONCLUSION: Although ultrasonography is commonly used to screen premature neonates for white matter injury, it was not a sensitive predictor of the milder spectrum of MR imaging-defined white matter abnormalities.

Birth Weight↗

Catalytic diastereoselective reductive claisen rearrangement.

[reaction: see text] A catalytic amount of [(cod)RhCl](2) and MeDuPhos initiates an ester enolate Claisen rearrangement with good yields and diastereocontrol. Reaction conditions are mild and tolerant of base-sensitive functionality.

Benzene Derivatives↗

Serial quantitative diffusion tensor MRI of the premature brain: development in newborns with and without injury.

PURPOSE: To determine the change over time of the apparent diffusion coefficient (ADC) and relative anisotropy of cerebral water in a cohort of premature newborns serially studied near birth and again near term. MATERIALS AND METHODS: Newborns were classified as normal (N = 11), minimal white matter injury (N = 7), or moderate white matter injury (N = 5). RESULTS: ADC decreased significantly with age in all brain regions in newborns classified as normal and those with minimal white matter injury. ADC increased with age or failed to decline in widespread areas of white matter in newborns with moderate white matter injury. Anisotropy increased with age in all white matter regions in newborns classified as normal. Anisotropy did not increase in frontal white matter in those with minimal white matter injury, and in widespread white matter areas in those with moderate white matter injury. CONCLUSION: This study demonstrates that serial diffusion tensor magnetic resonance imaging scans of premature newborns can detect differences in white matter maturation in infants with and without white matter injury.

Anisotropy↗

Predictors of 30-month outcome after perinatal depression: role of proton MRS and socioeconomic factors.

The objective was to determine in infants with perinatal depression whether the relative concentrations of N-acetylaspartate and lactate in the neonatal period are associated with (1) neurodevelopmental outcome at 30 mo of age or (2) deterioration in outcome from age 12 to 30 mo; and to determine whether socioeconomic factors are associated with deterioration in outcome. Thirty-seven term neonates were prospectively studied with single-voxel proton magnetic resonance spectroscopy of the basal nuclei and intervascular boundary zones. Thirty-month outcomes were classified as normal [if Mental Development Index of the Bayley Scales of Infant Development (MDI) >85 and neuromotor scores (NMS) <3; n = 15], abnormal [if MDI or=3 at 12 and 30 mo; n = 11], or deteriorated [if normal at 12 mo and abnormal at 30 mo (MDI or=3); n = 11]. Thirty percent (11/37) of our cohort deteriorated between 12 and 30 mo. N-acetylaspartate/choline decreased across the groups ordered as normal, deteriorated, and abnormal [in basal nuclei (p <or= 0.001) and intervascular boundary zones (p = 0.04)], but was not different between the normal and deteriorated groups (p = 0.08). Lactate/choline similarly increased across the groups [in basal nuclei (p = 0.01) and intervascular boundary zones (p = 0.05)]. The odds of deterioration, if normal at 12 mo, increased by a factor of 5.1 (95% confidence interval: 1.3-19.8) with each decrease in one of four household income strata. Infants with perinatal depression are at high risk of developmental deterioration between 12 and 30 mo of age, particularly if in a lower income home or with intermediate values of cerebral metabolites on neonatal proton magnetic resonance spectroscopy.

Apgar Score↗