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Washington State FAS Diagnostic & Prevention Network (FAS DPN) University of Washington Susan J. Astley Ph.D. Professor PowerPoint Presentation
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MRI, MRS, and fMRI in Children with FAS/D. Washington State FAS Diagnostic & Prevention Network (FAS DPN) University of Washington Susan J. Astley Ph.D. Professor and Director www.fasdpn.org. FASD MRI, MRS, fMRI Study. Institution:

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slide1

MRI, MRS, and fMRI in Children with FAS/D

Washington State

FAS Diagnostic & Prevention Network

(FAS DPN)

University of Washington

Susan J. Astley Ph.D.

Professor and Director

www.fasdpn.org

slide2

FASD MRI, MRS, fMRI Study

Institution:

University of Washington, FAS Diagnostic & Prevention Network

Investigators

Susan Astley Ph.D., Principal Investigator

Elizabeth Aylward, PhD, neuroimaging psychologist

Todd Richards, PhD, physicist

Ken Maravilla, MD, radiologist

Julian Davies, MD, pediatrician

Heather Carmichael Olson, PhD, psychologist

Kimberly Kerns, PhD, neuropsychologist

Allison Brooks, PhD, psychologist

Susan Dorn, MS, school psychologist

Tracy Jirikowic, OT, PhD, occupational therapist

Truman Coggins, PhD, speech language pathologist

Funding Agency

NIAAA

slide3

FASD MRI, MRS, fMRI Study: Hypotheses

  • Primary Hypotheses
  • The following will differ between children with FAS/D and typically developing children:
    • neuro-structure (size of specific brain structures)
    • neuro-function (as measured by psychological, psychiatric, and fMRI assessment)
    • neuro-chemistry (neurometabolites: choline and n-acetyl-aspartate)
  • Long-range Clinical Question
  • Can MRI, MRS, and/or fMRI improve the accuracy of a FASD diagnostic evaluation?
slide4

FASD MRI, MRS, fMRI Study: Population

  • STUDY POPULATION
  • Four groups (8-15 years old)
  • FAS / Partial FAS (n = 20)
  • Static Encephalopathy / Alcohol Exposed(SE/AE) (n = 24)(Severe “ARND” with no FAS face)
  • Neurobehavioral Disorder / Alcohol Exposed(ND/AE) (n = 21)(Mild “ARND” with no FAS face)
  • Controls (n = 16)(typical development, No alcohol exposure)
diagnostic method fasd 4 digit diagnostic code

CNS Damage

Diagnostic Method: FASD 4-Digit Diagnostic Code

Training4-Digit Online CourseDiagnostic Team Training

All Diagnostic Tools and Courses available on the web.www.fasdpn.org

slide6

3 4 4 4

significant severe definite 4

moderate moderate probable 3

mild mild possible 2

none none unlikely 1

Growth FAS Facial CNS

DeficiencyFeatures Damage

4 high risk

3 some risk

2 unknown

1 no risk

Prenatal

Alcohol

Growth Face CNS Alcohol

The FASD 4-Digit Diagnostic Code

Function

slide7

FASD MRI, MRS, fMRI Study: Population

Increasing severity of FASD across the 4 study groups

slide8

FAS

The Three FAS Facial Features

  • Short PFL <= -2 SD
  • 2) Smooth Philtrum Rank 4 or 5
  • 3) Thin Upper Lip Rank 4 or 5
slide9

FASD MRI, MRS, fMRI Study: Methods

  • METHODS
  • Five days of participation over the course of 1 month
  • Comprehensive psychological / psychiatric assessment
  • MRI, MRS, fMRI in scanner
slide10

FASD MRI, MRS, fMRI Study: Methods

PSYCHOLOGICAL / PSYCHIATRIC ASSESSMENTS:

Cognition, executive function, language, memory, achievement, attention, sensory-motor, inhibitory control, adaptive and maladaptive behavior.

Neuropsych.LanguageExperimentalBehavioral/Parent Report

WISC-III TLC Arrows Game BRIEF

CVLT-C TOLD Colored Boxes CBCL

DKEFS TOWK Fire Fighting Game C-DISC

RCFT Letters Game VABS

WCST Shapes Game

Key Math Child Size Ordering Test

QNST N-Back Faces

IVA CPT

VMI

slide11

FASD MRI, MRS, fMRI Study: Methods

MRI: Structure

Volumes

caudate

putamen

hippocampus

frontal lobe

frontal gray matter

frontal white matter

total brain

Midsaggital Area

corpus callosum

cerebellar vermis

total brain

slide12

FASD MRI, MRS, fMRI Study: Methods

  • fMRI: Functional Assessment in the Scanner
  • Whole brain scan for activity levels while child is participating in a N-back working memory task.
  • Child is presented photos of faces while in the scanner.
  • Child responds to task by pushing a button.
  • 0-Back Task
    • Push the button when you see a man’s face.
  • 1-Back Task
    • Push the button when the face you are looking at matches the face you saw one slide back.
  • 2-Back Task
    • Push the button when the face you are looking at matches the face you saw two slides back.
slide13

white matter voxel

FASD MRI, MRS, fMRI Study: Methods

  • MRS: Spectroscopy
  • Three locations scanned.
  • White matter voxel (1 cm cube)
  • Hippocampus voxel (1 cm cube)
  • Whole brain slice above the ventricles
  • Choline , N-acetyl-aspartate , Creatine
slide15

Mild ARND Severe ARND FAS / PFAS

Control ND/AE SE/AE FAS/PFAS

FASD MRI, MRS, fMRI Study: Results

Key Structural Findings

All brain regions become progressively smaller (absolute size) as you advance across the 4 Diagnostic Groups from Controls to FAS / PFAS.

slide16

Frontal Lobe (adjusted for brain size) Across 4 Groups

FAS/PFAS SE/AE ND/AE Control

FASD MRI, MRS, fMRI Study: Results

Key Structural Findings

The frontal lobe is significantly smaller in FAS/PFAS relative to Severe ARND, Mild ARND, and Controls, even after adjustment for overall brain size.

slide17

Caudate Size (adjusted for brain size) across the 4 Groups

FAS/PFAS SE/AE ND/AE Control

FASD MRI, MRS, fMRI Study: Results

Key Structural Findings

The caudate is significantly smaller in both FAS/PFAS and Severe ARND, relative to Mild ARND and Controls, even after adjustment for overall brain size.

slide18

FASD MRI, MRS, fMRI Study: Results

Key Structural Findings

NO significant group differences between 4 study groups for mean midsagittal area of corpus callosum.

Mean corpus callosum lengthdiffered between FAS/pFAS and Control groups

Of 207 FASD with clinical MRIs, only 2 cases (1%) with hypogenesis or agenesis of corpus callosum.

Variability in Shape of CC among Controls

slide19

FASD MRI, MRS, fMRI Study: Results

Key Structural Findings

Percent of subjects with one or more brain regions

significantly smaller than control group:

▪ FAS/PFAS (CNS Rank 3-4 with FAS facial features)70 %

▪SE/AE (CNS Rank 3, No FAS facial features) 58 %

▪ND/AE (CNS Rank 2, No FAS facial features) 43 %

▪Controls (CNS Rank 1, No FAS facial features) 0 %

Even subjects with neurobehavioral disorder (ND/AE)

have underlying structural alterations!

slide20

When will MR technology enter the FASD Diagnostic Clinic?

Before MRI can be used diagnostically,

we need population-based norms

(not research study norms)

to compare against.

What is the normal size of a frontal lobe in a 10 yr old boy?

If the frontal lobe is small, are there functional consequences?

The NIH MRI Study of Normal Brain Development.

Documenting normal MRI, MRS, and neuropsychological development in a population-based sample of healthy individuals (birth to 18 years old).

Waber et al., 2007 J Internationall Neuropsychological Society

slide21

FASD MRI, MRS, fMRI Study: Results

  • Key Structural-Functional Findings
  • Brain function decreases with decreasing size of brain regions.
  • One global measure of brain function is the 4-Digit CNS Ranks:
    • Rank 1 (normal function)
    • Rank 2 (mild impairment)
    • Rank 3 (severe impairment)
slide22

FASD MRI, MRS, fMRI Study: Results

Key Structural-Functional Findings

Some functional impairments appear correlated with reduction in size of specific brain regions.

slide23

FASD MRI, MRS, fMRI Study: Results

  • Key Structural-Functional Findings
  • Hippocampal volume
  • significantly smaller in all FASD groups
  • significantly correlated with performance on CVLT-C (r = .336, p < 0.01)
slide24

5 week 10 week

FASD MRI, MRS, fMRI Study: Results

Key Facial Findings

The frontal lobe decreases in size as the 4-Digit FAS face becomes more severe.

Frontal lobe and the FAS face both share the same embryologic origin (frontonasal prominence).

slide25

FASD MRI, MRS, fMRI Study: Results

Key Facial Findings

The more severe the FAS facial features, the more severe the impairment in brain function.

slide26

FASD MRI, MRS, fMRI Study: Results

One of Several Key Alcohol Findings

The frontal lobe volume decreases significantly with increasing duration of prenatal alcohol exposure.

Trimester of Exposure

slide27

FASD MRI, MRS, fMRI Study: Results

  • Key MR Spectroscopy Finding
  • Choline is significantly lower among FAS / PFAS (may be marker for white matter deficit).
  • Choline lower among those with alcohol exposure through the 2nd or 3rd trimester.

Choline and Group Choline and Trimester of Alcohol

slide28

Number of Correct Responses on N-Back

Level of Activation in Dorsolateral Prefrontal Cortex

Key:

1-Back (simple task)

2-Back (difficult task)

FASD MRI, MRS, fMRI Study: Results

One of Several fMRI Findings: Activation and Working Memory

fasd mri mrs fmri study
FASD MRI, MRS, fMRI Study:

Key Outcomes

  • Three clinically distinct groups can be constructed with the FASD 4-Digit Code (FAS, SE/AE, ND/AE). FAS is unique from ARND. ARND has 2 distinct subgroups (SE/AE and ND/AE).
  • Children across the full spectrum of FASD have evidence of structural brain alterations, not just those with FAS.
  • The FAS facial phenotype (as defined by the 4-Digit Code) is an external biomarker for underlying alteration in brain structure / function.
  • As dysfunction increases from mild, moderate, to severe, the prevalence / severity of underlying structural brain alteration increases linearly.
  • Frontal lobe, caudate, and hippocampus appeared most impacted.
  • Choline is significantly lower in FAS. May be a marker for white matter deficits.
  • Poor working memory performance was associated with lower activation on fMRI among FASD.
slide30

For Further Information

FASD Screening, Surveillance, Diagnosis, Intervention, Prevention, Training, Research, PublicationsGo to our websitewww.fasdpn.orgOr contact Susan Astley, Ph.D. astley@u.washington.edu