Lecture to introduce neuroimaging informatics for BMI 260, Stanford University, 5/8/2013

1. Neuroimaging Informatics
Vanessa Sochat
05/08/2013

3. Brains, the Final Frontier!
Neuroimaging Informatics

4. Neuroimaging Informatics
computational methods and infrastructure for
understanding the structure and function of the
brain

5. Neuroinformatics
FTW!
I have burning…
questions!
Neuroscience!
tools and databases
methods for analysis
computational models

6. I’ll take any
question to prove
my method!
I just want to
understand the
visual system

7. I will build you a
new spaceship!
I just discovered a
new nebula!

8. Captain’s Log
A Brief History
1989
What to do with
this data?

9. Captain’s Log
A Brief History
1989
What to do with
this data?
Here are some
ideas!
1991

10. Captain’s Log
A Brief History
1989
What to do with
this data?
Here are some
ideas!
1991
Fine! Here’s
grant $$$
1993
Neuroinformatics!

11. Captain’s Log
A Brief History
1989
What to do with
this data?
Here are some
ideas!
1991
Fine! Here’s
grant $$$
1993
Neuroinformatics!
2006
INCF

12. Captain’s Log
A Brief History
1989
What to do with
this data?
Here are some
ideas!
1991
Fine! Here’s
grant $$$
1993
Neuroinformatics!
2006
2013

13. Mission
• The Human Brain
• How do we image brains?
• How do we build tools?
UNCHARTED TERRITORY
HOW TO EXPLORE
NEUROINFORMATICS

14. Mission
• The Human Brain
• How do we image brains?
• How do we build tools?
BACKGROUND
DATA
METHODS

15. The Uncharted Territory:
The Human Brain

16. The Uncharted Territory
BACKGROUND DATA METHODS
Central Nervous System
(CNS)
Peripheral Nervous System
(CNS)

17. The Human Brain
BACKGROUND DATA METHODS

18. The Human Brain
BACKGROUND DATA METHODS
3 pounds <> 109 neurons <> 1015 synaptic connections

19. BACKGROUND DATA METHODS
The Human Brain

20. Anatomical Directions
BACKGROUND DATA METHODS
ANTERIOR POSTERIOR
SUPERIOR
INFERIOR
ROSTRAL
CAUDAL
VENTRAL
DORSAL
DORSAL

21. Slice it up!
BACKGROUND DATA METHODS
CORONAL SAGITTAL AXIAL

22. How to Explore:
Neuroimaging Methods

23. We study brains with Neuroimaging
BACKGROUND DATA METHODS
TEMPORAL RESOLUTION
SPATIALRESOLUTION

24. We don’t want to cut people open!
BACKGROUND DATA METHODS
Oh?

25. structure and function
BACKGROUND DATA METHODS
We collect data to answer a biological question
?
Population Protocol Data
What happens to the structure of region X as we get older?
What is my brain doing when I see pictures of cats?
Which regions are working together?
Public
Repository

26. structure and function
BACKGROUND DATA METHODS
We collect data to answer a biological question
?
Population Protocol Data
Public
Repository

27. BACKGROUND DATA METHODS
We like to identify biomarkers in our images
? Feature
Extraction
Public
Data
Process
Analysis /
Machine
Learning
Disorder diagnosis
Classification of subtypes of disease
Improved filtering methods
Understanding human connectome
Why?

28. We measure structure and function
BACKGROUND DATA METHODS
Invasive Non-invasive
Structure
sMRI
CT
DTI
Function
fMRI
PET
EEG
MEG

29. We measure structure and function
BACKGROUND DATA METHODS
Invasive Non-invasive
Structure
sMRI
CT
DTI
Function
fMRI
PET
EEG
MEG
sMRI
DTI
CT
fMRI EEG
PET
MEG

30. What imaging modalities do we
use to measure structure?

31. Computed Tomography
BACKGROUND DATA METHODS
CT
tumors
bones!
infarction
calcifications

32. Magnetic Resonance Imaging
BACKGROUND DATA METHODS
sMRI
gray matter
white matter
cerebrospinal fluid
T2
T1

33. Diffusion Tensor Imaging
BACKGROUND DATA METHODS
DTI
white matter integrity

34. What imaging modalities do we
use to measure function?

35. Functional Magnetic Resonance Imaging
BACKGROUND DATA METHODS
fMRI
neural activity   blood flow   oxyhemoglobin   MR signal

36. Positron Emission Tomography
BACKGROUND DATA METHODS
PET

37. Electroencephalography
BACKGROUND DATA METHODS
EEG

38. Magnetoencephalography
BACKGROUND DATA METHODS
MEG

39. What data do I need to measure…
BACKGROUND DATA METHODS
I want to measure… Imaging Modality
Some tissue volume sMRI (T1)
Tumor, bone, or fluid CT, sMRI (T2)
Cortical Thickness sMRI (T1)
White Matter Integrity DTI
Brain Function fMRI, with sMRI (T1) for registration
Superficial Activity EEG, MEG
Neurotransmitter-specific Activity PET

40. What does my data look like?

42. What does my data look like?
BACKGROUND DATA METHODS
TIME

43. What does my data look like?
BACKGROUND DATA METHODS
SLICE
VOXEL

44. What does my data look like?
BACKGROUND DATA METHODS
P Files
Imaging Data
Header
Nifti
• .nii (one file)
• .img / .hdr combo
3D
• .nii.gz (compressed file)
• .nii (uncompressed)
• .img/.hdr combos
4D

45. What are those numbers?!
• Structural
– Gray and white matter volume
– White Matter Integrity
– Cortical Thickness
• Functional
– Functional connectivity
– Blood flow

46. How we build tools:
Neuroimaging Informatics Methods

47. computational methods and infrastructure for
understanding the structure and function of the
brain
develop and apply new methods for acquisition,
representation, and analysis of neuroimaging
data and knowledge
BACKGROUND DATA METHODS
“What I want!”
“What I do!”

48. BACKGROUND DATA METHODS
IMAGE
ACQUISITION
PREPROCESSING PROCESSING ANALYSIS
Neuroimaging Informatics Pipeline
Data + Knowledge Representation + Infrastructure = Sharing, Knowledge, Tools
1 2 3

49. BACKGROUND DATA METHODS
IMAGE
ACQUISITION
PREPROCESSING PROCESSING ANALYSIS
Neuroimaging Informatics Pipeline
Data + Knowledge Representation + Infrastructure = Sharing, Knowledge, Tools
1 2 3

50. Segment
Realign and
Reslice
Coregister Normalize Smooth Segment
BACKGROUND DATA METHODS
Pre/Processing Prepares for Analysis

51. Realign and
Reslice
Coregister Normalize Smooth Segment
METHODS
Realignment for Motion Correction
DATABACKGROUND
translation rotation zooming shearingtranslation rotation

52. Realign and
Reslice
Coregister Normalize Smooth Segment
METHODS
Coregistration
DATABACKGROUND

53. Realign and
Reslice
Coregister Normalize Smooth Segment
METHODS
Normalization
DATABACKGROUND

54. Realign and
Reslice
Coregister Normalize Smooth Segment
METHODS
Smoothing
DATABACKGROUND
No smoothing 4 mm kernel

55. Realign and
Reslice
Coregister Normalize Smooth Segment
METHODS
Segmentation
DATABACKGROUND
Brain/skullCSFWMGM
Priors
Tissue Types

56. Realign and
Reslice
Coregister Normalize Smooth Segment
METHODS
Segmentation
DATABACKGROUND

57. BACKGROUND DATA METHODS
IMAGE
ACQUISITION
PREPROCESSING PROCESSING ANALYSIS
Neuroimaging Informatics Pipeline
Data driven approaches
Hypothesis drive approaches
1 2 3

58. ?
I’m getting
bigger!
BACKGROUND DATA METHODS
Two Analysis Approaches
Can we address my burning
question now?

59. What are commonly used apriori
methods?

60. BACKGROUND DATA METHODS
What are structural characteristics (e.g. gray matter volume,
density) within a brain region of interest in a subject
population?
?
VOXEL BASED MORPHOMETRY (VBM)
SEGMENT
NORMALIZE
MODULATE
SMOOTH
VOXEL-WISE STATISTICS
sMRI

61. BACKGROUND DATA METHODS
How are two or more brain regions of interest connected
anatomically in a subject population?
?
TRACTOGRAPHY (DTI)

62. BACKGROUND DATA METHODS
Which brain regions show neural activity during a function of
interest?
?
GENERAL LINEAR MODEL (GLM)
Brain regions responding “active”
to biological motion
REALIGN AND RESLICE
SEGMENT
REGISTER
NORMALIZE
FIT to GLM
sMRI and fMRI

63. BACKGROUND DATA METHODS
What is the brain network underlying a function of interest?
?
CORRELATIONS
Brain network underlying
hand movement
IDENTIFY ROI
EXTRACT SIGNAL
NETWORK
CONNECTIVITY

64. What are commonly used data-
driven methods?

65. BACKGROUND DATA METHODS
What is the brain network underlying a function of interest?
?
INDEPENDENT COMPONENT ANALYSIS (ICA)
X = A SX
n x m n x n
n x m
S = A-1 XX

66. BACKGROUND DATA METHODS
How and which set of brain regions cumulatively represent an
experimental stimuli?
?
MULTI VOXEL PATTERN ANALYSIS (MVPA)
fMRI

67. How do I use informatics to
extend my analyses?

68. Databases to Distribute Resources
BACKGROUND DATA METHODS
Publicly available Brain DBs:
fMRIDC
Allen Brain Atlas
BIRN
Neurosynth
ADNI
NDAR
Human Connectome
Demographics
Imaging
Protocol
Raw Images
Processed
Images

69. Atlas: Terms for Spatial Characteristics
BACKGROUND DATA METHODS
Brodmann Atlas ICBM Atlas

70. Knowledge Representation
BACKGROUND DATA METHODS
FMA
NIFSTD
XCEDE

71. Challenges, Captain!
BACKGROUND DATA METHODS
Complex, noisy
data! Arg!
Take that, poor
resolution!
Where are the
standards?!

72. BACKGROUND DATA METHODS
The Journey Continues…
PRESENTPAST FUTURE

74. I have questions…
vsochat@stanford.edu