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NIH MRI Study of Normal Brain Development

NIH MRI Study of Normal Brain Development AC Evans Ph.D. Brain Development Cooperative Group Pediatric Functional Neuroimaging: a Trans-NIH Workshop May 25, 2004 Contrast changes over time Problems with previous studies Sample sizes too small to detect subtle signals

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NIH MRI Study of Normal Brain Development

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  1. NIH MRI Study of Normal Brain Development AC Evans Ph.D. Brain Development Cooperative Group Pediatric Functional Neuroimaging: a Trans-NIH Workshop May 25, 2004

  2. Contrast changes over time

  3. Problems with previous studies • Sample sizes too small to detect subtle signals • Heterogeneity of subject population • Little longitudinal data • Lack of demographic representativeness • Limited behavioral data for brain-behaviour correlation • Limited MRI data (typically T1 only) • Usually limited analysis techniques

  4. The National Institute on Drug Abuse MRI Study of Normal Brain Development(N=500) Create a database of behavioral and brain MRI development data for 0-18 years Analyze structural-behavioural relationships Develop technique for dissemination of results

  5. Rationale for Project Design • Problem: Existing normative databases limited in size Pooling of databases difficult. Existing databases incompatible in • Slice thickness • Pulse sequence • Demographics • Behavioural tests One centre cannot collect large dataset fast enough to keep pace with technology • Solution: Clinical trial model: multi-centre acquisition, uniform protocol

  6. MRI Objectives • Objective 1: Anatomical MRI/Behavior (5-18) • Objective 2: Anatomical MRI/Behaviour (0-4) • Ancillary A: MR Spectroscopy • Ancillary B: Diffusion Tensor Imaging, Relaxometry

  7. Pediatric Study Centers (PSCs) • Neuropsychiatric Institute and Hospital, UCLA McCracken • Children’s Hospital, Boston Rivkin • Children’s Hospital of Philadelphia Wang • University of Texas-Houston Medical School Brandt • Children’s Hospital Medical Center, Cincinnati Ball • Washington University, St. Louis McKinstry

  8. Data Coordinating Center (DCC) • Overall Direction Evans • Database Zijdenbos, Vins, Charlet, Harlap, Das • Behavioral Liaison Leonard, Milovan • MRI Acquisition Pike, Arnaoutelis • MRI Analysis Collins, Kitching, Lerch • Sampling Plan Lange (Harvard) • Data Transfer Zeffiro, Van Meter (Georgetown) • Scientific Liaison Paus • Clinical Liaison Ad-Dab’bagh, Webster

  9. Clinical Coordinating Center (CCC) – St. Louis Recruitment, behavioral measures selection/certification, exclusions etc. for Obj 1,2 – Botteron, Almli Behavioral QC – Rainey, Henderson, Singer, Smith, Dubois, Warren, Edwards DTI Processing Center (DPC) - NIH Pierpaoli, Basser, Rohde, Chang MRS Processing Center (MPC) – UCLA (?) Alger, O’Neill

  10. NIH MRI Study of Normal Brain Development DCC CCC DPC

  11. Recruitment Procedure • Representative sample based on US 2002 census • Zip code demographic data • Telephone brief screener at recruitment • Telephone long screener for inclusion criteria • DISC, FIGS, CBCL • Hospital Visit (Neuro exam, Behaviour, MRI) • Objective 1 scans 3 times, every 2 years • Objective 2 scans 3-6 times • SES (3 levels) X age (0-18 yrs) X gender X ethnicity

  12. 60 50 40 30 20 10 0 4.5 6 7 8 9 10 11 12 13 14 15 16 17 18 Accrual by Age (Objective 1)

  13. Family Income (Raw) N = 409

  14. Parental Education N = 409 NIH MRI Study of Normal Pediatric Development US Population

  15. Ethnicity N = 409

  16. Behavioral Maturation is multi-dimensional

  17. MRI BEHAVIORAL T1W (Obj1+2+fallbacks) Full Interview T2W (Obj1+2+fallbacks) Bayley Mental Handedness PDW (Obj1+2+fallbacks) Bayley Motor JTCI MRS (Obj1+2) Bayley Behavioral Nepsy fluency MRSI (Obj1+2) Brief Interview Neurologicals DTI (Obj1+2) BRIEF Parent PSI Dual-contrast T2 (Obj2) CANTAB Pregnancy T1 Relaxometry (Obj2) Carey Purdue peg board T2 Relaxometry (Obj2) CBCL Tanner CVLT (C and II) TCI DAS Urine and Saliva DISC Digit span and coding DPS4 WASI Exclusion (Obj2) FIGS Woodcock-Johnson III Test Battery

  18. Study Organization Study Subject n-1 Subject n Subject n+1 Visit 1 Visit 2 … Visit n Exclusionary Screening Behavioral Instruments MRI Procedures CBCL DISC CBCL DPS4 JTCI CANTAB WJ3 WASI MRI MRI

  19. PSC DCC Mass Storage System Backup System Internet & DBMS Server(s) Study Work Station Data Warehouse MRI Scanner BVL BVL MRI INTERNET MRI MRI Data Marts MRI Console BVL Behavioral PC (laptop) Scientific Community Data Analysis Pipeline System Architecture

  20. New technology never works first time

  21. DCC-ID identifiedby candidate for each PSCID personal member of contains data on multiple visits recruited by SessionID Gender ethnic VisitNo psc DoB visit Objective EthnicID Weight CenterID Age stores data for a battery of administered MRI procedures & behavioral instruments Height ObjectiveID Objective MRI procedures behavioral battery of instruments bio figs apib das tanner psi cantab Screening Type DICOM T2W3D wisc exclus disc carey neuro wasi purdue cvltc MRS waisr MINC TestID brief int dps4 hand pls3 wj3 saliva cvlt2 MRSI header CommentID full int cbcl nepsy pregn bayley jtci urine T1W3D PD ScoreID Test ID Candidate Profile are identified by

  22. DBMS Software Platform • MySQL DBMS: • Cross-platform, open source • Robustness, speed, reliability • Low development cost • - Remote management • Graphical User Interface: • Cross platform, Internet enabled application • PHP-based application, complemented by • JavaScript, Java, and Perl for data • manipulation tasks. • Remote management, customizable

  23. Database GUI

  24. Database Summary • Low-cost, extensible, secure • 61 tests, approx. • 20,000 possible data fields (~1000 filled/subject) • Laptop-based behavioral test battery • Automatic MRI data transfer • Web-based behavioral GUI • Interactive 3D MRI web viewer • Automatic QC procedures • Project web site

  25. N=449 N=56 N=188 Obj 1 Obj 2 DTI

  26. Behavioral Instrument Status Total # of Instruments = 9827 Objective 1 = 9029 Objective 2 = 798 Total # in Database = 9827 As of May 20, 2004.

  27. 40 30 20 10 Std. Dev = 12.50 Mean = 110.6 N = 248.00 0 75.0 85.0 95.0 105.0 115.0 125.0 135.0 145.0 80.0 90.0 100.0 110.0 120.0 130.0 140.0 FIQ IQ Scores (n=248) FIQ: 110.7+0.8 VIQ: 109.9+08 PIQ: 108.9+0.8

  28. Summary of Behavioral QC

  29. W-J: Passage Comprehension (n=278) r=0.85, p=0.000

  30. WASI: Vocabulary (n=248) r=0.86, p=0.000

  31. Spatial Working Memory (CANTAB): Errors (n=250) r=-0.75, p=0.000

  32. Objective 1

  33. Objective 1 – MRS/I Objective 1 – DTI *Corrected to exclude the early Cincinnati and St. Louis 1 subjects since the DTI product was not available.

  34. Objective 2

  35. QC Overview • Goal: quick turn-around time • mean time for expedited review 1.5 days • median time over all subjects 7.0 days • Concentrated mostly on subject QC

  36. Inter-packet movement • Separate volume into packets • Register each packet to target • Resample and interpolate to 1mm slice thickness After Before

  37. Structural Probability Maps Functional Probability Maps Data Flow for Brain Mapping Data Acquisition : Reconstruction : Conversion to MINC Image Format PET fMRI aMRI Registration aMRI - ePET aMRI - tPET Frame alignment Inter-slice normalization T1/T2/PD/… alignment Registration aMRI - fMRI Partial volume correction Intensity non-uniformity correction Voxel-based model fitting Voxel-based coherence analysis 3D segmentation Stereotaxic Spatial Normalization Inter-volume normalization GLM analysis in 3, 4, or 5D

  38. Anatomical MRI analysis pipeline ASP

  39. Manual Auto INSECT ANIMAL SEAL ASP

  40. Objective 1 – classification

  41. Obj 1 – Tissue SPAMs (n=337)

  42. Age-related changes in WM density Paus et al, Science 1999; n=111 NIHPD; n=204; 16 1 0 t=10.5

  43. WM density and Spatial Working Memory: Between Errors (Age removed) NIHPD; n=188; 7 -1 66 t=-4.0

  44. Cortical Surface Extraction(Kim, Hanyang U.)

  45. Cortical Surface Extraction(Kim, Hanyang U.)

  46. Automated extraction of both cortical surfaces using CLASP algorithm (5 different brains)

  47. Analysis of detection limits • 19 T1 MRIs of the same subject (Colin Holmes) with 1mm isotropic sampling. • Computation of standard deviations across cortex. • Across blurring kernels. • Across metrics. • Power analysis: • N needed to recover change of 0.5 mm • Change required at N=25 in each group.

  48. Colin’s 19 Brains Average

  49. Required N to recover 0.5 mm Unblurred 5mm 10mm 20mm 200 0

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