All Hands Meeting 2005 Human Morphometry and Function BIRN Testbeds Christine Fennema-Notestine,...
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Transcript of All Hands Meeting 2005 Human Morphometry and Function BIRN Testbeds Christine Fennema-Notestine,...
All Hands Meeting 2005
Human Morphometry and Function BIRN Testbeds
Christine Fennema-Notestine, Ph.D.
Jessica Turner, Ph.D.
CBiO/BIRN Workshop 2006
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”
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 -> blood flows in -> the ratio changes
Slice Thicknesse.g., 6 mm
Number of Slicese.g., 10
SAGITTAL SLICE IN-PLANE SLICE
Field of View (FOV)e.g., 19.2 cm
VOXEL(Volumetric Pixel)
3 mm
3 mm6 mm
Slice Terminology
Matrix Sizee.g., 64 x 64
In-plane resolutione.g., 192 mm / 64
= 3 mm
From: http://defiant.ssc.uwo.ca/Jody_web/fmri4dummies.htm
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
Normal Elderly Control Alzheimer’s IndividualNormal Elderly Control Alzheimer’s Individual
Imaging Methods Derived data:
• Cortical thickness• Volumes of subcortical and
cortical gray and white matter• Shape derived metrics • Diffusion metrics of anisotropy
Bayesian segmentation using Gibbs priors. Temporal Lobe Left: coronal, right: sagittal.
Ventricle Thalamus Pallidum
Putamen
Cortical WM Amygdala
Hippocampus
Cortical GM
Cerebellar GM
Cerebellar WM
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
UCSDMGH/BWHWashU
Site
60 70 80 90
AGE
2000
3000
4000
5000
Lef
t-H
ipp
oca
mp
us
Hippocampal Volume Loss in Normal Aging
MBIRN priorities
To relate clinical assessments, cognitive function, and neuroanatomy within mBIRN’s 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
Existing neuroanatomical ontology
Need to create related “function”-based ontology
Brain
Cerebellum Cerebrum
Cerebral white matter …
Frontal cortex Temporal cortex
Superior temporal Mesial temporal
Amygdala Hippocampus
…
Cerebral cortex
…
…
…
Memory
CVLT
Brain
Cerebrum
Temporal
Mesial temporal
Hippocampus
Cerebral cortex
CVLT
Task and score description
Frontal Cognitiveimpairment
Cognition
Assessment
Neuropsychology
Amnesia
Memory Learning
Memory
Recognition
Recall
Free recall Cued Recall
CVLT
Retrieval
Hippocampus Frontal lobe
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
Statistical Mapsuperimposed on
anatomical MRI image
~2s
Functional images
Time
Condition 1
Condition 2 ...
~ 5 min
Time
fMRISignal
(% change)
ROI Time Course
Condition
Activation Statistics
Region of interest (ROI)
From http://defiant.ssc.uwo.ca/Jody_web/fmri4newbies.htm
30s-R30s-R30s-R30s-R Tap Tap TapTask
Image
Box-car Design: Comparing Active to Rest States
Stimulus (3Hz)...
Individual Time Courses
• Remove linear trends
• Scale as a percentage of the baseline
Learn
3t
1t
5t
3t
5t
1t
Encode 14 probes
37.8 + .2 at end”
Sample Run……(total time = 360”, including DDAs)Order of WM blocks randomized
0 2 1 3 8 9 7 2 4 . . .
7 * 5 * 4
* * 9 * *
Prompt
1.5” + .5”
Learn5t
3t
1t
+ + +…
Learn
fixfixfix fix fix
6”
2.7” each, 1.1 appearance, 1.6 jitter,minimum pre .300,response time for each probe =~1.5s
Average 12”, minimum 4”, max 20”,multiple of 2’’, randomized
total fix time = 78”
= 46”q block
2 blocks @ each WM load6 blocks = 276”
DDAs (6sec)
fix(14s)fix6
Cognitive working memory task (SIRP)
SIRP Recall Probe Contrasts (N=1)
P<.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
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
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
Clinical research questions define structure
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
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., Alzheimer’s), depression, learning disorders, etc.
• Provides numerous measures including: Recognition discriminability memory disorders, hippocampus, … Measurement of retention across time amnesia, Alzheimer’s, … Free recall of information retrieval, frontal lobe, Huntington’s,… Cued recall of information memory disorders, Alzheimer’s, … 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…
Highly complex assessment example
Bottom-up search:
User’s 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 doesn’t answer the user’s 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.
Top-down search:
User interested in studying the relationship between hippocampal volume and memory performance in Alzheimer’s 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
Brain
Cerebrum
Temporal
Mesial temporal
Hippocampus
Cerebral cortex
CVLT
Task and score description
Frontal Cognitiveimpairment
Cognition
Assessment
Neuropsychology
Amnesia
Memory Learning
Memory
Recognition
Recall
Free recall Cued Recall
CVLT
Retrieval
Hippocampus Frontal lobe
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)
Taxonomy of fMRI Experiments (from BrainMap)
Taxonomy of Experiments
Brain
Cerebellum Cerebrum
Cerebral white matter …
Frontal cortex Temporal cortex
Superior temporal Mesial temporal
Amygdala Hippocampus
…
Cerebral cortex
…
…
…
Memory
CVLT SIRP
Assessment
Behavioral Paradigm
Memory
CVLT SIRP
Assessment
Behavioral Paradigm
Cognitive Process
Attention
Working memory Long Term memory
SCID-Patient
Breathhold
Action
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)
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 Brodmann’s area, or a sulcal/gyral area, etc.). We’ll need to know how it was defined (Talairach atlas? MNI atlas? LONI atlas? Or subject-specific regions?) and what the statistic is.
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., Alzheimer’s) 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
Bottom-up search:
User’s 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 doesn’t answer the user’s 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
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
Brain
Cerebrum
Temporal cortex
Mesial temporal
Hippocampus
Cerebral cortex
MMSE
Cognitiveimpairment
Dementiaseverity
Cognition
Assessment
Neuropsychology
Alzheimer’s
Task and score description