Biomedical subjects

F L Bookstein

Publications and source records attributed to F L Bookstein.

At least 19 recordsLinked to original sources

PubMed2000

Augmented experimental pulse-spray thrombolysis with tissue plasminogen activator, enabling dose reduction by one or more orders of magnitude.

PURPOSE: To critically evaluate and optimize methodologic details of pulse-spray thrombolysis with tissue plasminogen activator (tPA) in a subacute rabbit inferior vena cava thrombosis model. MATERIALS AND METHODS: Occlusive inferior vena cava thrombi were produced in 104 rabbits and 2 days later were treated for 1 hour with pulse-spray thrombolysis using tPA. Methodologic variables included pulse frequency, concentration and amount of tPA, infusion versus pulse therapy, and admixture of heparin. After the rabbits were killed, residual thrombus was weighed. RESULTS: The authors' earlier standard regimen (3 mg of tPA in 6 mL of heparinized saline, 0.2-mL hand pulses, frequency 1 pulse per 2 minutes) produced 60% mean lysis. Optimization involved increasing the pulse frequency to two per minute and decreasing tPA concentration by 98% to 0.01 mg/mL, modifications that produced 22% more thrombolysis, despite 92% reduction in amount of tPA to 0.25 mg. CONCLUSION: Consistent with the in vitro work of other investigators, a roughly bell-shaped dose-response curve was elicited in vivo for pulse-spray with tPA. By diluting tPA to an optimal level, and increasing pulse frequency to two per minute, thrombolysis was markedly augmented. These results suggest that the conventional dose of tPA used for clinical pulse-spray thrombolysis can be reduced by one to two orders of magnitude, possibly markedly reducing procedural risk.

Animals↗

PubMed2000

Creases as local features of deformation grids.

To help identify underlying developmental or pathological processes, biological shape differences often are represented as diffeomorphisms of a Cartesian coordinate grid. The problem addressed here is the extraction of spatially discrete, localized, organized features of such transformation grids. Some features can be identified with variants of the singularity (x, y) --> (x, x2y + y) that are visually evident as creases in suitably enhanced grid diagrams. The crease is a non-generic singularity at which a pair of cusps appears as a function of a parameter for extrapolation. The examples here show how these representations extract statistically informative and scientifically helpful features from deformations that help characterize two brain diseases, schizophrenia and Fetal Alcohol Syndrome, in two dimensions. Under smoothing by relaxation of bending energy against Euclidean distance, one analogue to multiscale analysis for discrete punctate data, creases are robust in location and orientation.

Brain↗

PubMed2000

On categorizations in analyses of alcohol teratogenesis.

In biomedical scientific investigations, expositions of findings are conceptually simplest when they comprise comparisons of discrete groups of individuals or involve discrete features or characteristics of individuals. But the descriptive benefits of categorization become outweighed by their limitations in studies involving dose-response relationships, as in many teratogenic and environmental exposure studies. This article addresses a pair of categorization issues concerning the effects of prenatal alcohol exposure that have important public health consequences: the labeling of individuals as fetal alcohol syndrome (FAS) versus fetal alcohol effects (FAE) or alcohol-related neurodevelopmental disorder (ARND), and the categorization of prenatal exposure dose by thresholds. We present data showing that patients with FAS and others with FAE do not have meaningfully different behavioral performance, standardized scores of IQ, arithmetic and adaptive behavior, or secondary disabilities. Similarly overlapping distributions on measures of executive functioning offer a basis for identifying alcohol-affected individuals in a manner that does not simply reflect IQ deficits. At the other end of the teratological continuum, we turn to the reporting of threshold effects in dose-response relationships. Here we illustrate the importance of multivariate analyses using data from the Seattle, Washington, longitudinal prospective study on alcohol and pregnancy. Relationships between many neurobehavioral outcomes and measures of prenatal alcohol exposure are monotone without threshold down to the lowest nonzero levels of exposure, a finding consistent with reports from animal studies. In sum, alcohol effects on the developing human brain appear to be a continuum without threshold when dose and behavioral effects are quantified appropriately.

Central Nervous System Depressants↗

PubMed2000

Three-dimensional Bolton-Brush Growth Study landmark data: ontogeny and sexual dimorphism of the Bolton standards cohort.

OBJECTIVE: The treatment of craniofacial reconstructive surgery patients may benefit from comparison to average referent three-dimensional landmark data. These data may be useful for diagnosis, treatment planning, prosthetic design, or outcomes assessment. With regard to subadult patients, we hypothesize that the pattern of ontogenetic shape change of same sex, same ethnicity, referent populations will show gross uniformity. We present a preliminary shape analysis of 50 three-dimensional landmarks derived from 317 Bolton-Brush Growth Study biorthogonal image pairs. We determine which landmarks can be collected from scanned radiographs reliably by four operators for the precisely locatable points, ontogenetic trends in landmark configuration shape change, and patterns of sexual dimorphism. PARTICIPANTS: Participants were Bolton standards individuals (16 male and 16 female) who contributed biplane cephalograms seven or more times with annual or greater spacing between ages 3 and 18 years. DESIGN: After removing outliers, we searched for ontogenetic heterogeneity, including sexual dimorphism and within sex-specific Procrustes coordinate shape spaces. RESULTS: A cut-off of 4.3-mm interoperator error left 32 landmarks in our analysis. Three different approaches (principal component analysis, age-trend analysis, and principal components of age residuals) all found no patterns of individual variation around sex-specific average trends of shape change. Male shape change peaks at age 15, a correlate of the growth spurt. CONCLUSIONS: Simultaneous frontal and lateral anatomic landmark identification improves three-dimensional localization reliability. Three-dimensional craniodental shape change from ages 8 to 18 within the Bolton standards presents little heterogeneity. Considerations of ethnicity aside, these may be initial grounds for use of these data as a normative referent.

Adolescent↗

PubMed1999

Landmark-based morphometric analysis of first-episode schizophrenia.

BACKGROUND: The goal of this investigation was to utilize landmark-based shape analysis and image averaging to determine the sites and extent of specific structural changes in first-episode schizophrenia. METHODS: Neuroanatomic structures identified on midsagittal magnetic resonance imaging (MRI) scans were compared between 20 patients with schizophrenia and 22 normal control subjects. The difference between averaged landmark configurations in the two groups was visualized as a shape deformation by a thin-plate spline and through averaged MRI images for both groups. RESULTS: A shape difference was found to be statistically significant; by inspection, it is contrast between differences in two closely abutting regions, involving primarily the posterior corpus callosum and upper brain stem--the "focus" is the relation between them. CONCLUSIONS: The findings are consistent with prior studies suggesting involvement in schizophrenia of the corpus callosum and the limbic structures contributing to the corpus callosum; the possibility of local pathology primarily involving the brain stem cannot be excluded. The methods of landmark-based shape analysis and image averaging utilized in this study can complement the "region-of-interest" method of investigating morphometric abnormalities by characterizing the spatial relationships among structural brain abnormalities in schizophrenia.

Adolescent↗

PubMed1999

Three-dimensional magnetic resonance-based morphometrics and ventricular dysmorphology in schizophrenia.

BACKGROUND: Recent methodological refinements in magnetic resonance (MR) imaging have led to brain averaging and morphometric approaches that are sensitive to subtle anatomical distinctions in schizophrenia. METHODS: Using a novel morphometric technique for surface analysis, 48 selected landmarks of the rendered ventricular system were extracted and compared between the ventricles of 20 patients with schizophrenia and 20 normal subjects. RESULTS: There was no significant difference in ventricular shape between groups, but significant (p = .015) and highly localized shape deformity was detected at the foramen of Monro and at the proximal temporal horn of the lateral ventricle of male (but not female) patients relative to controls. CONCLUSIONS: Three-dimensional MR-based morphometrics complements established volumetric approaches and can detect minute shape deformities that may be associated with schizophrenia.

Adolescent↗

PubMed1999

Identification of neural circuits underlying P300 abnormalities in schizophrenia.

Event-related potentials (ERPs) provide a noninvasive method to evaluate neural activation and cognitive processes in schizophrenia. The pathophysiological significance of these findings would be greatly enhanced if scalp-recorded ERP abnormalities could be related to specific neural circuits and/or regions of the brain. Using quantitative approaches in which scalp-recorded ERP components are correlated with underlying neuroanatomy in schizophrenia, we focused on biophysical and statistical procedures (partial least squares) to relate the auditory P300 component to anatomic measures obtained from quantitative magnetic resonance imaging. These findings are consistent with other evidence that temporal lobe structures contribute to the generation of the scalp-recorded P300 component and that P300 amplitude asymmetry over temporal recording sites on the scalp may reflect anatomic asymmetries in the volume of the superior temporal gyrus in schizophrenia.

Brain Mapping↗

PubMed1999

Long-term effects of nasoalveolar molding on three-dimensional nasal shape in unilateral clefts.

OBJECTIVE: This objective of this study was to determine the effect of presurgical nasoalveolar molding on long-term nasal shape in complete unilateral clefts. DESIGN: The study was retrospective, and the subjects were chosen at random. Nasal casts of the subjects were scanned in three dimensions. Each nose was best fit to its mirror image, and a numerical asymmetry score was determined. SETTING: All patients were treated at the Institute of Reconstructive Plastic Surgery, NYU Medical Center, New York, New York. PATIENTS: The study subjects (n = 10) were selected from a group that had undergone presurgical nasal molding in conjunction with alveolar molding. The control subjects (n = 10) were selected from a group that had undergone presurgical alveolar molding alone. INTERVENTIONS: All subjects underwent presurgical orthopedic treatment until the age of approximately 4 months at which time the primary surgery was performed. MAIN OUTCOME MEASURE: The nasal shape following nasal molding should be more symmetrical than if molding had not been done. RESULTS: The mean asymmetry index for the nasoalveolar molding group was 0.74, and the control group was 1.21. This difference was statistically significant (p < .05). CONCLUSIONS: Presurgical nasoalveolar molding significantly increases the symmetry of the nose. The increase in symmetry is maintained long term into early childhood. The limitations of this study include (1) asymmetry alone is not an adequate shape result in most situations, (2) the children evaluated in this study were not fully grown, and (3) the control group was not age matched.

Alveolar Process↗

PubMed1999

Individual differences in auditory and visual attention among fetal alcohol-affected adults.

BACKGROUND: Deficits in attention are commonly identified among patients who have been prenatally exposed to alcohol, and they often affect the ability of the patients to function appropriately in society. METHODS: Eleven adult patients with fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE) were compared with nine adult subjects with no history of prenatal alcohol exposure, using four tests of visually and auditorially mediated attention. RESULTS: In relation to the comparison group, patients with FAS/FAE exhibited substantial deficits in both auditory and visual attention; the auditory deficits were greater. We observed two predominant patterns of deficits among patients with FAS/FAE, one involving both auditory and visual attention problems and the other involving less severe auditory problems and even fewer visual problems. Most subjects with FAS or FAE had some manifestations of attention problems in at least one of the tests of attention used in this study. We present a new graphical representation of individual auditory Continuous Performance Test data across a 6-min period, which, compared with conventional scores, more clearly reveals the markedly disrupted and variable attention patterns displayed by some individuals with FAS or FAE. CONCLUSIONS: These findings suggest that detailed analysis of the pattern of individual performance for each subject is an important aspect of Continuous Performance Test assessment. Our findings further suggest that intellectual performance (intelligence quotient score) alone is not sufficient to account for the patterns of disrupted attention for individuals with FAS/FAE. Assessment of individuals with FAS or FAE should include measurement of attentional functioning in both the visual and auditory modalities.

Adult↗

PubMed1998

Average African American three-dimensional computed tomography skull images: the potential clinical importance of ethnicity and sex.

The production of average 'normative' three-dimensional (3D) computed tomography surface images of the bony skull has only recently been explored. The authors wish to determine the effect of using sex- and ethnicity-specific adult average 3D skull images for comparisons with patient images at various stages of craniofacial surgical management (i.e., diagnosis, treatment planning, prosthetic design, image-guided operative procedures, and outcomes assessment). Craniofacial surgical reconstruction for abnormal patterns of development, cancer resection, or trauma are most likely to benefit from these comparisons. To morphometrically test the significance of separating normative 3D skull data by sex and ethnicity, the authors collected 52 3D, anatomical landmarks from 3D computed tomography scans of dry skulls of 20 Americans of European ethnicity and 20 Americans of primarily African (i.e., primarily African and some European) ethnicity. A Procrustes-based morphometric analysis of shape detects 1.2 times as much interethnic variance as intersex variance. The African American sample presents 4.2% more dolichocephaly, wider orbits, flatter nasal area, larger gnathic anatomy, and more procumbent dentition. Pooling the sexes across both groups, it is seen that men tend to have less bulbous crania, more protruding brows, noses, and masticatory muscle attachments, and relatively less protrusive palettes and anterior mandibles. Despite a small sample size (N = 40), the authors' results are statistically significant (P approximately 0.001 overall) for both of the main factors, sex and ethnicity, separately.

Adolescent↗

PubMed1998

A fetal alcohol behavior scale.

This research aimed to develop a Fetal Alcohol Behavior Scale (FABS) that describes the behavioral essence of fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE), regardless of age, race, sex, and IQ. Using a reference sample of 472 diagnosed patients with FAS or FAE, ages 2 to 51, five studies are described. The FABS demonstrates high item-to-scale reliability (Cronbach's alpha = 0.91) and good test-retest reliability (r = 0.69) over an average interval of 5 years. It identifies many of the subjects with known or presumed prenatal alcohol exposure in detection studies using both prison and general samples. FABS scores also predict dependent living among adult patients with FAS/FAE. The FABS is uncorrelated with IQ, sex, age, race, and diagnosis (FAS versus FAE). We outline areas of further work to define the specificity and utility of this FABS.

Adolescent↗

PubMed1998

Prenatal alcohol exposure and family history of alcoholism in the etiology of adolescent alcohol problems.

OBJECTIVE: To examine the relative importance of prenatal alcohol exposure and family history of alcoholism for the prediction of adolescent alcohol problems. METHOD: In 1974-75, a population-based, longitudinal prospective study of alcohol and pregnancy began with self-report of alcohol use by pregnant women. In a 14-year follow-up, 439 parents provided information on the family history of alcohol problems for these adolescent offspring. The 14-year-old adolescents provided information on the frequency and quantity of their own alcohol consumption within the past month, on the consequences of their drinking over the past 3 years, and on their age at first intoxication. Additional covariates were assessed prenatally and at follow-up. RESULTS: Prenatal alcohol exposure was more predictive of adolescent alcohol use and its negative consequences than was family history of alcohol problems. Prenatal exposure retained a significant predictive effect even after adjustment for family history and other prenatal and environmental covariates. By contrast, the nominally significant correlation of family history with adolescent drinking is weaker after adjustment for prenatal alcohol exposure and disappears entirely after adjustment for other relevant covariates. We observed no evidence for an interactive effect of fetal exposure and family history in predicting adolescent alcohol use. CONCLUSIONS: Fetal alcohol exposure is a risk factor for adolescent alcohol involvement and alcohol-related problems and may account for variance in prediction of problems otherwise attributed to family history of alcoholism. Studies of alcoholism etiology and family history need to include consideration of even modest levels of fetal alcohol exposure.

Adolescent↗

PubMed1998

Neuropsychological deficits in adolescents with fetal alcohol syndrome: clinical findings.

Understanding the nature of cognitive deficits among adolescent patients with fetal alcohol syndrome (FAS) can direct future research on assessment and intervention. In an exploratory study, nine nonretarded teenagers with FAS were administered tests of IQ and adaptive behavior, and neuropsychological tests presumed sensitive to alcohol effects. Their performance was compared with psychometric norms and to data from a sample of 174 adolescents with minimal or no prenatal alcohol exposure. These nonretarded FAS patients commonly showed behavior problems, decreased social competence, and poor school performance. Neuropsychological testing revealed significant deficits, although no one neuropsychological profile characterized all patients and not all tests revealed problems. Relatively intact performance was observed in procedural memory, some measures of reaction time, and some reading measures. Deficits were seen on attentional and memory tasks tapping visual-spatial skills, short-term auditory attention and memory, declarative learning, and cognitive flexibility and planning. Difficulties in processing speed and accuracy were also seen. Comparison with a subgroup of 52 nonalcohol-exposed or minimally alcohol-exposed adolescents with a similar range of IQ scores demonstrated that deficits among these FAS patients were not fully explained by a general lowering of IQ.

Adolescent↗

PubMed1997

Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder.

We critique published incidences for fetal alcohol syndrome (FAS) and present new estimates of the incidence of FAS and the prevalence of alcohol-related neurodevelopmental disorder (ARND). We first review criteria necessary for valid estimation of FAS incidence. Estimates for three population-based studies that best meet these criteria are reported with adjustment for underascertainment of highly exposed cases. As a result, in 1975 in Seattle, the incidence of FAS can be estimated as at least 2.8/1000 live births, and for 1979-81 in Cleveland, approximately 4.6/1,000. In Roubaix, France (for data covering periods from 1977-1990), the rate is between 1.3 and 4.8/1,000, depending on the severity of effects used as diagnostic criteria. Utilizing the longitudinal neurobehavioral database of the Seattle study, we propose an operationalization of the Institute of Medicine's recent definition of ARND and estimate its prevalence in Seattle for the period 1975-1981. The combined rate of FAS and ARND is thus estimated to be at least 9.1/1,000. This conservative rate--nearly one in every 100 live births--confirms the perception of many health professionals that fetal alcohol exposure is a serious problem.

Female↗

PubMed1997

Landmark methods for forms without landmarks: morphometrics of group differences in outline shape.

Morphometrics, a new branch of statistics, combines tools from geometry, computer graphics and biometrics in techniques for the multivariate analysis of biological shape variation. Although medical image analysts typically prefer to represent scenes by way of curving outlines or surfaces, the most recent developments in this associated statistical methodology have emphasized the domain of landmark data: size and shape of configurations of discrete, named points in two or three dimensions. This paper introduces a combination of Procrustes analysis and thin-plate splines, the two most powerful tools of landmark-based morphometrics, for multivariate analysis of curving outlines in samples of biomedical images. The thin-plate spline is used to assign point-to-point correspondences, called semi-landmarks, between curves of similar but variable shape, while the standard algorithm for Procrustes shape averages and shape coordinates is altered to accord with the ways in which semi-landmarks formally differ from more traditional landmark loci. Subsequent multivariate statistics and visualization proceed mainly as in the landmark-based methods. The combination provides a range of complementary filters, from high pass to low pass, for effects on outline shape in grouped studies. The low-pass version is based on the spectrum of the spline, the high pass, on a familiar special case of Procrustes analysis. This hybrid method is demonstrated in a comparison of the shape of the corpus callosum from mid-sagittal sections of MRI of 25 human brains, 12 normal and 13 with schizophrenia.

Algorithms↗

PubMed1997

Association of prenatal alcohol exposure with behavioral and learning problems in early adolescence.

OBJECTIVE: To examine the association of moderate levels of prenatal alcohol exposure with learning and behavior in early adolescence. METHOD: A population-based cohort of 464 children were followed longitudinally from birth to age 14 years. Alcohol exposure was assessed via in-depth maternal self-report in the fifth month of pregnancy. At age 14, learning and behavior were assessed with multiple measures, tapping parent, teenager, and psychologist viewpoints, drawn from adolescent laboratory examination and parent phone interview. The underlying pattern of association between prenatal alcohol and adolescent outcome was detected using partial least-squares statistical techniques; confounding factors were dealt with by regression methods. RESULTS: Analyses revealed a statistically significant, subtle relationship between greater prenatal alcohol use and increased behavior/learning difficulties during adolescence, even after accounting for other developmental influences. "Binge" maternal drinking and exposure early in pregnancy were associated with a profile of adolescent antisocial behavior, school problems, and self-perceived learning difficulties. CONCLUSIONS: Fetal alcohol exposure (even at "social drinking" levels) is associated with developmental difficulties in adolescence that are consistent with problems seen earlier in life. Clinicians should understand the potential role prenatal alcohol exposure plays in behavioral and cognitive problems.

Adolescent↗

PubMed1996

Spatial relationships of neuroanatomic landmarks in schizophrenia.

Two new morphometric techniques, landmark-based shape analysis and landmark-based image averaging, were applied to magnetic resonance images (MRIs) to investigate the sites and extent of structural neuropathology in schizophrenia. These analyses allow the identification of averaged anatomy through joint registration on multiple landmarks simultaneously. MRI scans obtained in the midsagittal plane were compared between 14 patients with schizophrenia and 14 normal subjects. The relation between averaged landmark configuration in the two groups was visualized as a deformation. There were no large-scale shape abnormalities noted, although the patients had significantly smaller brains. The data suggest that the neuroanatomic abnormality associated with schizophrenia, in the midsagittal plane, is circumscribed (focal), involving primarily the region of the posterior corpus callosum, upper brainstem, and quadrigeminal cistern. Also, the thickness of the corpus callosum is reduced all along its length. The findings are consistent with prior studies suggesting involvement in schizophrenia of the cerebellum, the corpus callosum and, possibly, the limbic structures contributing to the corpus callosum. The methods of image averaging and shape analysis used in this study complement the 'region of interest' method of investigating morphometric abnormalities by characterizing the precise locations and spatial relationships among relevant structural brain abnormalities in schizophrenia.

Adult↗

PubMed1996

Spatial pattern analysis of functional brain images using partial least squares.

This paper introduces a new tool for functional neuroimage analysis: partial least squares (PLS). It is unique as a multivariate method in its choice of emphasis for analysis, that being the covariance between brain images and exogenous blocks representing either the experiment design or some behavioral measure. What emerges are spatial patterns of brain activity that represent the optimal association between the images and either of the blocks. This process differs substantially from other multivariate methods in that rather than attempting to predict the individual values of the image pixels, PLS attempts to explain the relation between image pixels and task or behavior. Data from a face encoding and recognition PET rCBF study are used to illustrate two types of PLS analysis: an activation analysis of task with images and a brain-behavior analysis. The commonalities across the two analyses are suggestive of a general face memory network differentially engaged during encoding and recognition. PLS thus serves as an important extension by extracting new information from imaging data that is not accessible through other currently used univariate and multivariate image analysis tools.

Algorithms↗