Human Morphometry and Function BIRN Testbeds

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Human Morphometry and Function BIRN Testbeds

• Christine Fennema-Notestine, Ph.D.
• Jessica Turner, Ph.D.

CBiO/BIRN Workshop 2006
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MBIRN/FBIRN Ontology Needs

• GOAL User will employ BIRN interface and
  Mediator to perform scientific queries on data
  from
• structural and functional MRI experiments,
• clinical assessments,
• psychiatric interviews,
• and/or behavioral experiments
• BIRN needs for common vocabularies
• Mediator needs to talk across databases to find
  relevant/similar information this requires
  linking of concepts to table columns and values
• Query interface needs semantic network to find
  related information
• Example queries
• Find all datasets of schizophrenics with
  structural and functional imaging data related to
  working memory
• Find the correlation between hippocampal volume
  and working memory performance in AD subjects

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MRI Scanner

• Structural images, such as T1, PD, T2
• Measures of function, e.g., Blood Oxygenation
  Level Dependent (BOLD) signal

• FMRI
• Measures the ratio of oxygenated/deoxygenated
  hemoglobin in the blood
• Neurons fire -gt blood flows in -gt the ratio
  changes

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Slice Terminology
From http//defiant.ssc.uwo.ca/Jody_web/fmri4dumm
ies.htm
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Clinical Neuroimaging Problems of mBIRN

• To develop the capability to analyze as a single
  data set MRI and associated data acquired across
  multiple sites, using tools developed at multiple
  sites
• Examine clinical, demographic, and genetic
  correlates of human neuroanatomical data
• Emphasis on depression, mild cognitive
  impairment, and AD

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Imaging Methods Derived data

• Cortical thickness
• Volumes of subcortical and
  cortical gray and white
  matter
• Shape derived metrics
• Diffusion metrics of anisotropy

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Common studies of structural data

• Examine the relationship between normal aging and
  hippocampal volume
• Using a combination of volumetric measures and
  clinical data, predict classification of
  individuals as healthy controls or individuals
  with AD

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MBIRN priorities

• To relate clinical assessments, cognitive
  function, and neuroanatomy within mBIRNs
  multi-site AD sample, with future branching into
  neuropsychiatric measures (e.g., fBIRN
  schizophrenia interviews, etc.).
• The common acronym for the "California Verbal
  Learning Test" (a neuropsychological assessment
  of learning and memory) "CVLT" needed to be added
  as a synonym.
• More importantly, the CVLT concept only has
  defined relationships with the concept
  "Assessment Scales" and links to other
  assessments scales no meaningful relationships
  are between this measure and the concepts for
  cognitive (memory), anatomical (hippocampus), or
  disease (AD) terms

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Existing neuroanatomical ontology
Brain

• Need to create related function-based
  ontology

Cerebellum
Cerebrum
CVLT
Cerebral white matter

Cerebral cortex

Frontal cortex
Temporal cortex
Memory
Mesial temporal

Superior temporal

Amygdala
Hippocampus
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Assessment
Brain
Neuropsychology
Cerebrum
Amnesia
Cognition
Cerebral cortex
Frontal
Temporal
Cognitive impairment
Memory
Learning
Mesial temporal
CVLT
Hippocampus
Task and score description
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Memory
CVLT
Recognition
Retrieval
Recall
Free recall
Cued Recall
Frontal lobe
Hippocampus
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Functional Imaging Methods

• T2-weighted, gradient-echo echo-planar imaging
  sequence
• TE 40 ms, TR 3 sec, Flip Angle 90
• Acquisition matrix 141 x 64, interpolated to 256
  x 256
• Final in-plane pixel size 0.94 x 0.94 mm2
• Slice thickness 5 mm
• 14-16 axial slices covering the superior half of
  the cortex
• Image acquisitions 70

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Activation Statistics
Functional images
Time
From http//defiant.ssc.uwo.ca/Jody_web/fmri4newbi
es.htm
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Box-car Design Comparing Active to Rest States
Stimulus
(3Hz)...
Tap
Tap
Tap
Task
30s-R
30s-R
30s-R
30s-R
Image
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Individual Time Courses

• Remove linear trends
• Scale as a percentage of the baseline

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Cognitive working memory task (SIRP)
37.8 .2 at end
1.5 .5
46q block
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Encode
14 probes
Prompt
2 blocks _at_ each WM load 6 blocks 276
0 2 1 3 8 9 7 2 4 . . .
Learn
5t
Learn
2.7 each, 1.1 appearance, 1.6 jitter, minimum
pre .300, response time for each probe 1.5s
7 5 4
3t
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Learn
1t
5t
5t
3t
3t
DDAs (6sec)
1t
1t
fix
fix
fix
fix
fix
fix(14s)
fix
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Sample Run (total time 360, including
DDAs) Order of WM blocks randomized

Average 12, minimum 4, max 20, multiple of
2, randomized total fix time 78
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SIRP Recall Probe Contrasts (N1)
Plt.001, uncorrected, ext Green Set 5 Set
3 Red Set 3 Set 1 Results or derived data
storage still being standardized. --with fMRI,
can analyze a single subject, or groups of
subjects
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Human BIRN data includes

• Participant demographics such as age, gender,
• Clinical and psychiatric information
• Assessments used, data type
• Diagnostic information
• Behavioral data during fMRI tasks
• Need to know how to interpret that (is a button
  1 response a yes or a no?)
• Raw structural and functional images
• Need information about data collection and
  preprocessing methods
• Single-subject and group level analyses and
  results
• Need information about analytic methods used

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Clinical research questions define structure

• Bottom-up
• ? When reviewing data, user questions what a
  given assessment measures and what the score
  means.
• Must include assessment name as a term that will
  link to clinical data provenance information
  (task description and score interpretation)
• Must provide link to term for assessed
  function(s) (cognitive, behavioral, psychiatric
  domain)
• Must provide link to potentially related brain
  regions
• User could then simply enter assessment name to
  find description and related clinical and
  anatomical terms

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• Top-down
• ? User investigates brain-behavior
  relationships, e.g., between the hippocampus and
  memory performance
• Must include cognitive terms such as cognitive
  assessment, memory, recognition, recall
• Link terms to existing assessment terms (e.g.,
  CVLT)
• Link as appropriate to neuroanatomical ontology
  (e.g., hippocampus)
• User could then search via specific cognitive
  domain or through hippocampus to reach relevant
  assessments

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Highly complex assessment example

• California Verbal Learning Test (CVLT)
• Comprehensive assessment of memory and learning
• Widely used, often in head injury including
  frontal lobe damage, amnesia, dementia (e.g.,
  Alzheimers), depression, learning disorders,
  etc.
• Provides numerous measures including
• Recognition discriminability ? memory disorders,
  hippocampus,
• Measurement of retention across time ? amnesia,
  Alzheimers,
• Free recall of information ? retrieval, frontal
  lobe, Huntingtons,
• Cued recall of information ? memory disorders,
  Alzheimers,
• Response bias ? malingering, depression,
  motivation,
• Serial position effects ? short term memory,
  primacy recency effects,
• Single trial learning? learning disorders,
  attention, frontal lobe,
• Learning over several trials ? retention, frontal
  lobe, hippocampus,
• Semantic organization ? association cortex,
  superior temporal lobe,
• and more

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Bottom-up search

• Users dataset contains the CVLT what does it
  measure?
• Search for CVLT
• Related to PARENT concepts like
  Neuropsychological tests or Assessment Scales
  or SIBLING concepts of other tests
• What is the CVLT? This doesnt answer the users
  question.
• Need relationship links to function memory and
  learning
• Addition of terms covered under memory and
  learning such as recognition, recall, attention,
  motivation, serial position effects, episodic
  memory, semantic memory, will be related to
  various subscores of this test
• Need relationship links to structure anatomical
  regions reflected in change of performance on
  this measure ? hippocampus
• Link by subscore and/or by overall measure
• E.g., CVLT can assess recognition memory,
  usually linked to hippocampus, but also
  retrieval of information, often linked to
  frontal lobe function.

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Top-down search

• User interested in studying the relationship
  between hippocampal volume and memory performance
  in Alzheimers disease.
• Search for measures of memory
• Would like to see memory linked to CVLT
• Would like to see memory linked to hippocampus at
  a very basic level
• Would like to see links to potential disorders
  assessed, e.g., amnesia or AD

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Assessment
Brain
Neuropsychology
Cerebrum
Amnesia
Cognition
Cerebral cortex
Frontal
Temporal
Cognitive impairment
Memory
Learning
Mesial temporal
CVLT
Hippocampus
Task and score description
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Memory
CVLT
Recognition
Retrieval
Recall
Free recall
Cued Recall
Frontal lobe
Hippocampus
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Data gathering from federated databases

• Find all the schizophrenic subjects with fMRI
  data doing a working memory task.
• This involves
• Demographics Find database tables which contain
  Age, Gender, Handedness, Diagnosis, etc.
• Clinical aspects What clinical assessments were
  used to measure schizophrenia symptoms?
• Cognitive taxonomies Which tasks are working
  memory tasks?
• Scanning parameters
• Type of scan structural, functional
• If structural, what kind of scan SPGR? Other?
• If functional Transversal of k-space Linear?
  Spiral? Other?
• And other imaging parameters, e.g. TR, TE,
  Number of slices? (whole brain or single-slab?),
  Slice thickness/gap thickness, Slice acquisition
  order (interleaved or serial)

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Taxonomy of fMRI Experiments (from BrainMap)
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Taxonomy of Experiments
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Brain
Behavioral Paradigm
Assessment

Cerebellum
Cerebrum
SIRP
CVLT
Cerebral white matter

Cerebral cortex

Frontal cortex
Temporal cortex
Memory
Mesial temporal

Superior temporal

Amygdala
Hippocampus
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Behavioral Paradigm
Assessment
SCID-Patient
SIRP
CVLT
Breathhold
Long Term memory
Working memory
Memory
Attention
Cognitive Process
Action
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The issue of multiple identifiers

• A cerebellum cannot be a thalamus
• But a cognitive task can be
• a measure of both working memory and attention
  (e.g., SIRP)
• a measure of both recognition memory and
  executive retrieval (e.g., CVLT)
• and reflected then by more than one anatomical
  region
• Other issues crossing domains
• memory is associated with the hippocampus,
  generically, but is much more complex requiring
  neural circuits
• working memory activation patterns from the SIRP
  are not found in the hippocampus (and everyone
  knows that)

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Ontology Experiences

• Derived fMRI data Mean activations or some such
  summary data (z-scores, e.g.) for various
  cortical regions (ROIs) may be stored as a result
  of single-subject analysis.
• That way, the activation in various cortical
  areas can be summarized and data mining and
  other techniques then can be applied.
• In the short-term, users will probably download
  the data or analyses and extract the results
  using their preferred methods.
• In the long term, however, that will become
  infeasible
• the databases will have to be made interoperable
  with standard datamining software.
• This is where the neuroanatomy ontologies come
  in.
• We will need to know what the ROI is and which
  naming scheme it came from (e.g., a Brodmanns
  area, or a sulcal/gyral area, etc.). Well need
  to know how it was defined (Talairach atlas? MNI
  atlas? LONI atlas? Or subject-specific regions?)
  and what the statistic is.

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Basic clinical assessment example

• Mini-mental State Examination (MMSE Folstein et
  al., 1975 )
• Brief standardized measure of cognitive status
• to monitor progression/stabilization in medical
  setting
• to screen research participants
• Often used in cognitive disorders and dementia
  (e.g., Alzheimers) or other illnesses not
  disease specific
• Relatively non-specific relationship to general
  brain changes
• Usually reflected as a single score
• Based on brief assessment of orientation,
  attention, immediate recall, short term recall,
  language, ability to follow simple verbal
  commands

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Bottom-up search

• Users resultant dataset contains the MMSE the
  user asks what does it measure?
• Search for MMSE concept
• Related to PARENT concepts like
  Neuropsychological tests or Assessment Scales
  or SIBLING concepts of other tests
• What is the MMSE? This doesnt answer the users
  question.
• Need relationship links to function general
  cognitive ability, cognitive impairment, dementia
  severity, brain damage
• Need relationship links to structure anatomical
  regions reflected in change of performance on
  this measure, although a relatively non-specific
  measure ? brain

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Top-down search

• What variables exist that would provide a measure
  of general cognitive function and dementia
  severity?
• Search for measures of (general) cognitive
  function
• Would like to see general cognitive ability,
  cognitive impairment, dementia severity linked to
  MMSE
• Would like to see general cognitive ability,
  cognitive impairment, dementia severity linked to
  neuroanatomical regions, simply brain in this
  case
• Would like to see links to potential disorders
  measured, e.g., AD

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Assessment
Brain
Cognition
Neuropsychology
Cerebrum
Cerebral cortex
Alzheimers
Temporal cortex
Dementia severity
Cognitive impairment
Mesial temporal
MMSE
Hippocampus
Task and score description