Automated cerebellar segmentation: Validation and application to detect smaller volumes in children prenatally exposed to alcohol

Objective To validate an automated cerebellar segmentation method based on active shape and appearance modeling and then segment the cerebellum on images acquired from adolescents with histories of prenatal alcohol exposure (PAE) and non-exposed controls (NC). Methods Automated segmentations of the total cerebellum, right and left cerebellar hemispheres, and three vermal lobes (anterior, lobules I–V; superior posterior, lobules VI–VII; inferior posterior, lobules VIII–X) were compared to expert manual labelings on 20 subjects, studied twice, that were not used for model training. The method was also used to segment the cerebellum on 11 PAE and 9 NC adolescents. Results The test–retest intraclass correlation coefficients (ICCs) of the automated method were greater than 0.94 for all cerebellar volume and mid-sagittal vermal area measures, comparable or better than the test–retest ICCs for manual measurement (all ICCs > 0.92). The ICCs computed on all four cerebellar measurements (manual and automated measures on the repeat scans) to compare comparability were above 0.97 for non-vermis parcels, and above 0.89 for vermis parcels. When applied to patients, the automated method detected smaller cerebellar volumes and mid-sagittal areas in the PAE group compared to controls (p < 0.05 for all regions except the superior posterior lobe, consistent with prior studies). Discussion These results demonstrate excellent reliability and validity of automated cerebellar volume and mid-sagittal area measurements, compared to manual measurements. These data also illustrate that this new technology for automatically delineating the cerebellum leads to conclusions regarding the effects of prenatal alcohol exposure on the cerebellum consistent with prior studies that used labor intensive manual delineation, even with a very small sample.

[1]  Tim Cootes,et al.  An Introduction to Active Shape Models , 2000 .

[2]  Richard Coppola,et al.  Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test: A positron emission tomography study , 1995, Neuropsychologia.

[3]  E. Riley,et al.  Prenatal exposure to alcohol affects the ability to maintain postural balance. , 1998, Alcoholism, clinical and experimental research.

[4]  A. Streissguth,et al.  Pattern of Malformation in Offspring of Chronic Alcoholic Mothers , 1995, Alcohol health and research world.

[5]  M. Hallett,et al.  Memory in patients with cerebellar degeneration , 1993, Neurology.

[6]  Lindsay M. Squeglia,et al.  Recent binge drinking predicts smaller cerebellar volumes in adolescents , 2013, Psychiatry Research: Neuroimaging.

[7]  Julia A. Scott,et al.  A comprehensive volumetric analysis of the cerebellum in children and adolescents with autism spectrum disorder , 2009, Autism research : official journal of the International Society for Autism Research.

[8]  G. M. Halliday,et al.  Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke's encephalopathy , 1999, Neuroscience.

[9]  Ulla Ruotsalainen,et al.  Automatic cerebral and cerebellar hemisphere segmentation in 3D MRI: Adaptive disconnection algorithm , 2010, Medical Image Anal..

[10]  C. Goodlett,et al.  Alcohol-induced Purkinje cell loss depends on developmental timing of alcohol exposure and correlates with motor performance. , 1998, Brain research. Developmental brain research.

[11]  A. Toga,et al.  Mapping cerebellar vermal morphology and cognitive correlates in prenatal alcohol exposure , 2005, Neuroreport.

[12]  A. Cerasa,et al.  Cerebellar Atrophy in Essential Tremor Using an Automated Segmentation Method , 2009, American Journal of Neuroradiology.

[13]  S E Petersen,et al.  A positron emission tomography study of the short-term maintenance of verbal information , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  Stephen M. Smith,et al.  Bayesian statistical models of shape and appearance for subcortical brain segmentation , 2007 .

[15]  E. Riley,et al.  Neuropsychological Comparison of Children with Heavy Prenatal Alcohol Exposure and an IQ-Matched Comparison Group , 2011, Journal of the International Neuropsychological Society.

[16]  F Debaere,et al.  Cerebellar and premotor function in bimanual coordination: parametric neural responses to spatiotemporal complexity and cycling frequency , 2004, NeuroImage.

[17]  Daniel Rueckert,et al.  Generalised Overlap Measures for Assessment of Pairwise and Groupwise Image Registration and Segmentation , 2005, MICCAI.

[18]  P. Brugger,et al.  Cerebellum and Source Memory , 2010, European Neurology.

[19]  C. Goodlett,et al.  A single day of alcohol exposure during the brain growth spurt induces brain weight restriction and cerebellar Purkinje cell loss. , 1990, Alcohol.

[20]  Geraldine Dawson,et al.  Cerebellar vermal volumes and behavioral correlates in children with autism spectrum disorder , 2009, Psychiatry Research: Neuroimaging.

[21]  F. Bookstein,et al.  Damage to the human cerebellum from prenatal alcohol exposure: the anatomy of a simple biometrical explanation. , 2006, Anatomical record. Part B, New anatomist.

[22]  B. Cragg,et al.  A CHANGE IN SUSCEPTIBILITY OF RAT CEREBELLAR PURKINJE CELLS TO DAMAGE BY ALCOHOL DURING FETAL, NEONATAL AND ADULT LIFE , 1982, Neuropathology and applied neurobiology.

[23]  Robert M. Haralick,et al.  Textural Features for Image Classification , 1973, IEEE Trans. Syst. Man Cybern..

[24]  E. Riley,et al.  Neuromuscular responses to disturbance of balance in children with prenatal exposure to alcohol. , 1998, Alcoholism, clinical and experimental research.

[25]  S. Petersen,et al.  Practice-related changes in human brain functional anatomy during nonmotor learning. , 1994, Cerebral cortex.

[26]  T. Jernigan,et al.  Abnormal development of the cerebellar vermis in children prenatally exposed to alcohol: size reduction in lobules I-V. , 1996, Alcoholism, clinical and experimental research.

[27]  B. Cragg,et al.  A CHANGE IN SUSCEPTIBILITY OF RAT CEREBELLAR PURKINJE CELLS TO DAMAGE BY ACETALDEHYDE DURING FETAL, NEONATAL AND ADULT LIFE , 1982, Neuropathology and applied neurobiology.

[28]  J. Soares,et al.  Brain anatomy and development in autism: review of structural MRI studies , 2003, Brain Research Bulletin.

[29]  B. Volk,et al.  Alcohol embryo- and fetopathy Neuropathology of 3 children and 3 fetuses , 1979, Journal of the Neurological Sciences.

[30]  George Fein,et al.  Controlling for premorbid brain size in imaging studies: T1-derived cranium scaling factor vs. T2-derived intracranial vault volume , 2004, Psychiatry Research: Neuroimaging.

[31]  Scott T. Grafton,et al.  Automated image registration: I. General methods and intrasubject, intramodality validation. , 1998, Journal of computer assisted tomography.

[32]  T. Heeren,et al.  Age at drinking onset and alcohol dependence: age at onset, duration, and severity. , 2006, Archives of pediatrics & adolescent medicine.

[33]  E. Riley,et al.  Children with heavy prenatal alcohol exposure exhibit deficits when regulating isometric force. , 2012, Alcoholism, clinical and experimental research.

[34]  E. Riley,et al.  Children with heavy prenatal alcohol exposure have different frequency domain signal characteristics when producing isometric force. , 2013, Neurotoxicology and teratology.

[35]  J. West,et al.  Temporal vulnerability of fetal cerebellar Purkinje cells to chronic binge alcohol exposure: ovine model. , 2007, Alcoholism, clinical and experimental research.

[36]  K. Wisniewski,et al.  A clinical neuropathological study of the fetal alcohol syndrome. , 1983, Neuropediatrics.

[37]  Neeraj Sharma,et al.  Automated medical image segmentation techniques , 2010, Journal of medical physics.

[38]  Stephen M. Smith,et al.  Accurate, Robust, and Automated Longitudinal and Cross-Sectional Brain Change Analysis , 2002, NeuroImage.

[39]  Stephanie Powell,et al.  Registration and machine learning-based automated segmentation of subcortical and cerebellar brain structures , 2008, NeuroImage.

[40]  D. Delis,et al.  Fetal alcohol syndrome: a case report of neuropsychological, MRI and EEG assessment of two children. , 1992, Alcoholism, clinical and experimental research.

[41]  Jennifer M. Blackwell,et al.  Fetal alcohol exposure and temporal vulnerability: regional differences in cell loss as a function of the timing of binge-like alcohol exposure during brain development. , 1999, Alcoholism, clinical and experimental research.

[42]  E. Riley,et al.  Children with heavy prenatal alcohol exposure experience reduced control of isotonic force. , 2013, Alcoholism, clinical and experimental research.

[43]  O. Salonen,et al.  MRI findings in children with school problems who had been exposed prenatally to alcohol , 2002, Developmental medicine and child neurology.

[44]  J. Troendle,et al.  A prospective cohort study of the prevalence of growth, facial, and central nervous system abnormalities in children with heavy prenatal alcohol exposure. , 2012, Alcoholism, clinical and experimental research.

[45]  Colin Studholme,et al.  Differential effects of intraventricular hemorrhage and white matter injury on preterm cerebellar growth. , 2011, The Journal of pediatrics.

[46]  D. Timmann,et al.  Evaluation of a new approach for semi-automatic segmentation of the cerebellum in patients with multiple sclerosis , 2012, Journal of Neurology.

[47]  J. Altman,et al.  Ethanol-induced reductions in cerebellar growth of infant rats , 1975, Experimental Neurology.

[48]  J. Holton,et al.  Selective damage to the cerebellar vermis in chronic alcoholism: a contribution from neurotoxicology to an old problem of selective vulnerability , 1997, Neuropathology and applied neurobiology.

[49]  Robert Peharz,et al.  Fidgety movements - tiny in appearance, but huge in impact. , 2016, Jornal de pediatria.

[50]  HyunWook Park,et al.  An automatic cerebellum extraction method in T1-weighted brain MR images using an active contour model with a shape prior. , 2011, Magnetic resonance imaging.

[51]  C. Goodlett,et al.  Regional differences in the timing of dendritic outgrowth of Purkinje cells in the vermal cerebellum demonstrated by MAP2 immunocytochemistry. , 1990, Brain research. Developmental brain research.

[52]  Adolf Pfefferbaum,et al.  The SRI24 multichannel atlas of normal adult human brain structure , 2009, Human brain mapping.

[53]  Stefan Klein,et al.  Automated Brain Structure Segmentation Based on Atlas Registration and Appearance Models , 2012, IEEE Transactions on Medical Imaging.

[54]  T. Jernigan,et al.  A decrease in the size of the basal ganglia following prenatal alcohol exposure: a preliminary report. , 1994, Neurotoxicology and Teratology.

[55]  H. Rusinek,et al.  Functional magnetic resonance imaging of human brain activity in a verbal fluency task , 1998, Journal of neurology, neurosurgery, and psychiatry.

[56]  Andrew D Arenson,et al.  Collaborative initiative on fetal alcohol spectrum disorders: methodology of clinical projects. , 2010, Alcohol.

[57]  E. Sowell,et al.  Further development of a neurobehavioral profile of fetal alcohol spectrum disorders. , 2013, Alcoholism, clinical and experimental research.

[58]  E. Riley,et al.  Motor response programming and movement time in children with heavy prenatal alcohol exposure. , 2010, Alcohol.

[59]  Timothy F. Cootes,et al.  Active Appearance Models , 2001, IEEE Trans. Pattern Anal. Mach. Intell..

[60]  Sarah N. Mattson,et al.  Fetal Alcohol Spectrum Disorders: Neuropsychological and Behavioral Features , 2011, Neuropsychology Review.

[61]  Brian Patenaude,et al.  Bayesian statistical models of shape and appearance for subcortical brain segmentation , 2007 .

[62]  J. West,et al.  The effects of the timing of ethanol exposure during the brain growth spurt on the number of cerebellar Purkinje and granule cell nuclear profiles. , 1993, Alcoholism, clinical and experimental research.

[63]  F. Bookstein,et al.  Effects of prenatal alcohol exposure on fine motor coordination and balance: A study of two adult samples , 2006, Neuropsychologia.

[64]  B. B. Andersen.  Reduction of Purkinje cell volume in cerebellum of alcoholics , 2004, Brain Research.

[65]  Jörn Diedrichsen,et al.  A probabilistic MR atlas of the human cerebellum , 2009, NeuroImage.

[66]  E P Riley,et al.  Brain dysmorphology in individuals with severe prenatal alcohol exposure , 2001, Developmental medicine and child neurology.

[67]  E. Riley,et al.  Accuracy of the Diagnosis of Physical Features of Fetal Alcohol Syndrome by Pediatricians After Specialized Training , 2006, Pediatrics.

[68]  S. M. Sumi,et al.  Brain malformations related to prenatal exposure to ethanol. , 1978, The Journal of pediatrics.