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AGING AND ITS EFFECTS ON THE BRAIN

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Title: AGING AND ITS EFFECTS ON THE BRAIN


1
AGING AND ITS EFFECTS ON THE BRAIN
  • Prepared by
  • Seniha Esen Yuksel
  • CVIP Lab
  • August 2004

2
Why Aging?
  • Gray hair, wrinkled skin, changes in bone
    structure, discomfort, suffering.
  • Is it going go be possible to define when and
    where the aging starts?
  • Can we develop protective factors to slow down
    the changes?
  • Can we define the patterns of diseases such as
    Alzheimer, Schizophrenia, Multiple Schlerosis,
    Alcoholism and AIDS related dementia, and
    separate these patterns from the aging process?

3
OUTLINE
  • Brain basics
  • Effects of aging
  • Studies
  • Diseases

4
As we get older, we encounter
  • Decrease in the total brain weight volume
  • Cortical thinning
  • Gyral atrophy
  • Widening of sulci
  • Expansion of ventricular volume
  • Neurological disorders

5
BRAIN BASICS
  • Gray matter is the cortex of the brain which
    contains nerve cell bodies.
  • White matter contains lots of nerve fibers that
    are sheathed in a white fatty insulating protein
    called myelin.
  • Cerebrospinal fluid (CSF) is the fluid that
    surrounds the central nervous system, 100-140 ml
    in adults

6
Terms we should remember
  • Gyrification is the folding of the brain.
  • Gyrus is a bump on the cortex (pl gyri)
  • Sulcus is a groove (cut) (pl sulci).

Lobes Frontal thinking, planning Parietal
pressure, pain, touch, taste Occipital Visual
information Temporal Hearing, memory
7
Ventricles
If the brain is cut in cross section, there are 4
Cavities in it the 4 ventricles Lateral
ventricles, 3rd ventricle and 4th ventricle.
Images http//www.epub.org.br/cm/n02/fundamentos/
ventriculos_i.htm
8
Ventricles in MRI
9
OUTLINE
  • Brain basics
  • Effects of aging
  • Studies
  • Diseases

10
Evolution of Aging Problem
  • Until 1984s, aging is related to the loss of
    neurons in the brain.
  • Ex 100.000 neuron loss daily resulting in
    19.7 loss at the age of 80 Brody et al..
  • With the advancements of neuron counting
    technology, Terry et al. found out that there is
    not much age related neural loss in cortex.
  • The small decrease has been explained as the
    cortical thinning or as the structural changes in
    neurons as they lose their dendritic trees and
    spines with age.

11
Evolution of Aging Problem II
  • So the studies were concentrated on areas that
    are more likely to get affected by the aging
    process
  • Frontal Lobe Thinking and planning
  • Temporal Lobe Hearing and memory
  • Gray/white matter loss as the reason for the
    brain shrinkage (atrophy) weight loss
  • Gray matter is where the information processing
    is done.
  • White matter is the communication channel.

12
More about the gray matter.
  • Cerebral cortex is made up of gray matter!
  • Gray matter is composed of the neurons.
  • Gray matter (GM) is the place where the actual
    processing is done.
  • Individuals over 60 years old have 17 lighter
    brains than of young adults due to the shrinking
    of the cerebral cortex, i.e. gray matter loss!

13
Why does GM or WM losses occur?
  • It is believed that the gray matter (GM) loss
    occurs due to the decrease in the size of large
    neurons (rather than a notable decrease in the
    number of neurons).
  • White Matter (WM) loss occurs due to damage of
    myelinated fibers with age.

14
What else happens?
  • As we get older, we encounter
  • Decrease in the total brain weight volume
  • Cortical thinning (Decrease in gray matter)
  • Gyral atrophy (Thinning of gyri)
  • Widening of sulci
  • Expansion of ventricular volume
  • Neurological disorders
  • Image http//w3.ouhsc.edu/pathology/DeptLabs/pick
    .htm

15
OUTLINE
  • Brain basics
  • Effects of aging
  • Studies
  • Diseases

16
Types of studies
  • On the specific parts of the brain such as the
    cerebellum and brain stem.
  • Studies on the segmentation and quantification of
    gray matter and white matter
  • Gray matter studies
  • Gyrification problem Folding of the brain
  • Cortical thinning Distance between gray white
    matter
  • White matter studies

17
Regional Segmentation Brain Stem Cerebellum
Analysis (Luft et al.)
  • First brainstem is segmented, then cerebellum is
    segmented.
  • Both segmentations are composed of 3 steps
  • Structural boundaries not defined by different
    signal intensities are manually traced.
  • For the structural boundaries of the brainstem
    anatomical landmarks and planes are used to make
    the process automatic.
  • For the cerebellum, the boundary was redrawn
    manually on every image.

18
Regional Segmentation Brain Stem Cerebellum
Analysis (Luft et al.)
  • Segmentation contd
  • contrast-defined boundaries are automatically
    segmented using a region-growing algorithm in
    three dimensions
  • A 3D lattice is used to subdivide the cerebellum
    into 11 regions.
  • V1, V2, V3 Vermis 1,2,3
  • IH Lateral Hemisphere
  • MH Medial Hemisphere
  • Results Cerebellum shrinks with age, brain stem
    stays stable.
  • Automatic regional segmentation is not easy.

19
Types of studies
  • On the specific parts of the brain such as the
    cerebellum and brain stem.
  • Studies on the segmentation and quantification of
    gray matter and white matter
  • Gray matter studies
  • Gyrification problem Folding of the brain
  • Cortical thinning Distance between gray white
    matter
  • White matter studies

20
Problems with GMWM Segmentation
  • Partial Volume Effect
  • Buried Cortex
  • Veins and Nerve Fibers
  • Inhomogeneities in the magnetic field in MR
    images.
  • Preservation of the form for surgical purposes

21
Segmentation ProblemsPartial volume effect (PVM)
  • Multiple tissues contribute to a single pixel ?
    called PVM.
  • Resulting intensity is the weighted average of
    the different tissues present.
  • PVM occurs due to the finite resolution of the
    scanner.
  • It can be reduced by decreasing the voxel size
    and by application of sub-voxel techniques

Illustration of partial volume effect a) Ideal
Image b) Acquired image
22
Segmentation ProblemsBuried Cortex
  • Buried cortex is the main problem in measuring
    the gyrification.
  • The edges of gyral crowns touch one another and
    the inside is filled with CSF.
  • Surface rendering programs can distinguish a and
    b, but they will fail to detect atrophy if
  • GM pixels touch one another (c)
  • there is a deep folding due to high gyrification
    (d).

23
Gray Matter White Matter Analysis
  • Three types of studies on GM-WM analysis
  • Gray Matter Studies Gyrification and Thinning of
    Cerebral Cortex
  • GM and WM Segmentation
  • WM Segmentation With Tissue Examination

24
GM Studies Gyrification (Magnotta et al)
  • Folding increases by age to increase surface area
    and functional capacity.
  • Quantitative measurements of gyrification can
    provide important information on aging.
  • Magnotta et al.(1999) has the first study to
    examine the changes in sulcal and gyral shape
    quantitatively.

25
GM Studies Gyrification
  • The main problem in measuring the gyrification is
    the 'problem of buried cortex'.
  • Magnotta et al. solved this problem by
    introducing erosion to the entire brain surface
    so that the gyral crowns don't touch each other.
  • Then GM and WM are segmented by fuzzy and sharp
    classifiers.

Figure An illustration of a normal brain (A) and
an atrophic brain (B), with the sulci and gyri
outlined. Note that in the atrophic brain the
gyri, shown in red, are more steeply curved and
the sulci, shown in blue, are more flattened.
26
GM Studies Gyrification
  • In the third step, a cortical isosurface is
    generated for measurements.
  • To preserve the topology, new vertices are added
    to the existing surface by local
    retriangulations.

Fig The surface visualization. The right image
illustrates how sulci are opened up and buried
cortex is eliminated. Sulci shown in blue and
gyri in red.
FigThe effects of retiling the cortical
iso-surface.
27
GM Studies Gyrification
  • In the fourth step the curvature measure is
    calculated.
  • Curvature measure determines if the triangles are
    convex of concave by the following formulation
    The curvature measure is the average over all j
    of
  • i and j the centers of the neighbor triangles
  • ? the angle between the normal to triangle i and
    the vector from i to j.
  • This formula gives the curvature index. The
    convex (positive) values represent gyri, concave
    (negative) values represent sulci.
  • Finally, the surface area is calculated as the
    sum of the areas of the triangles.
  • The distance between each triangle and GM/WM
    interface gives the cortical thickness.

28
GM Studies Gyrification
  • Results
  • Sulcal curvature index becomes increasingly more
    negative, reflecting a flattening and opening up
    of the sulci
  • Gyral curvature index becomes increasingly more
    positive, reflecting a narrowing of the gyral
    crowns and a sharpening of their curvature
  • And the cortex becomes progressively thinner.

Figure sulcal curvature, gyral curvature,
cortical thickness vs. age plots.
29
Gray Matter White Matter Analysis
  • Three types of studies on GM-WM analysis
  • Gray Matter Studies Gyrification and Thinning of
    Cerebral Cortex
  • GM and WM Segmentation
  • WM Segmentation With Tissue Examination

30
GM Studies Thinning of Cerebral Cortex
  • Dale et al. introduced the first complete,
    automated procedure to make cortical analysis.
  • Sub-cortical regions (extensions of GM) are cut
    out deforming an ellipsoidal template into the
    shape of the inner surface of the skull.
  • White matter is extracted by the use of connected
    components
  • The resulting volume is deformed to form the
    GM/WM surface.
  • But this surface deviates from the spherical
    shape so these topological defects are manually
    corrected.
  • Using this method, Salat et al. found that the
    global cortical thickness and global cortical
    volume declines by increasing age.

Fig Intersection of the tesselated white matter
surface and pial surfaces with the skull-stripped
MRI volume.
31
GM Studies Thinning of Cerebral Cortex II
  • Xu et al. , Kruggel et al., Zeng et al. also give
    automated methods but they are not applied to the
    aging problem.
  • Zeng applied a level set method with coupled
    surfaces to segment both boundaries in a single
    step.
  • Kruggel used marching tetrahedra algorithm to
    compute the surface of the WM.
  • Marching tetrahedra algorithm is a method where
    triangulated surface meshes are used.
  • Then he used deformable models to obtain an
    improved model of WM.
  • He calculated the cortical thickness by
    projecting a vertex of GM mesh onto the triangles
    of WM mesh along its plane normal.
  • Kruggels and Zengs results are not consistent
    with each other.

32
Gray Matter White Matter Analysis
  • Three types of studies on GM-WM analysis
  • Gray Matter Studies Gyrification and Thinning of
    Cerebral Cortex
  • GM and WM Segmentation
  • WM Segmentation With Tissue Examination

33
GM WM Segmentation
  • Ge et al. supports both the GM and the WM
    contributes to the brain atrophy.
  • GM, WM and intracranial space volumes were each
    identified as individual 3D fuzzy connected
    objects according to their
  • Affinity
  • Fuzzy adjacency
  • Hanging togetherness

Figure A) Original dual-echo FSE proton
density-weighted image. B) T2-weighted MR image.
C) Total intracranial volume image.
D) CSF volume image. E) GM volume image. F) WM
volume image
34
GM WM Segmentation
  • Results
  • To predict WM and GM as quadratic functions of
    age, least-squares regression was implemented
  • WM decreases in a quadratic fashion with a
    greater rate in the adult midlife
  • GM volume loss appears as linear function of age
    throughout adult life.

35
Gray Matter White Matter Analysis
  • Three types of studies on GM-WM analysis
  • Gray Matter Studies Gyrification and Thinning of
    Cerebral Cortex
  • GM and WM Segmentation
  • WM Segmentation With Tissue Examination

36
Only WM matters in aging
  • Peters et al. explains the conflicts in many of
    the papers as segmentation errors partial
    volume effect.
  • This study examines the tissue sections from the
    same brains.
  • Partial volume effect is reduced by decreasing
    the voxel size to 0.7mm (previous studies used
    1-1.5mm).
  • Results
  • No loss of gray matter (consistent with the fact
    that there is no or little neuron loss with age)
  • Significant loss of white matter especially in
    frontal lobes, and a decrease in ventricular
    size.
  • Conclusion
  • Loss in the brain comes from the loss of
    myelinated nerve fibers.
  • These changes in white matter could result in a
    disconnection syndrome and contribute to the
    cognitive decline in normal aging.
  • If alterations in myelin and myelinated nerve
    fibers could be decreased, than some of the
    cognitive decline associated with normal aging
    can be avoided.

37
Types of studies
  • On the specific parts of the brain
  • On quantification of gray matter and white matter
  • Gray matter studies
  • Gyrification problem Folding of the brain
  • Cortical thinning Distance between gray white
    matter
  • GM and WM Segmentation
  • White Matter Segmentation With Tissue Examination

38
OUTLINE
  • Brain basics
  • Effects of aging
  • Studies
  • Diseases

39
Brain Disorders / Diseases
  • Alzheimer
  • Multiple Schlerosis
  • Schizophrenia
  • Alcoholism and AIDS related dementia
  • Corticobasal Degeneration (CBD)
  • Progressive Supranuclear Palsy (PSP)
  • (possible collaboration with medical school)

40
Brain disorders Progressive Supranuclear Palsy
(PSP)
  • PSP is an under-recognized brain disorder.
  • Symptoms Slowing of movement and reduced control
    of walking, balance, swallowing, speaking and eye
    movement.
  • Typically begin in ones 60s
  • No effective medication.
  • Causes are not known. A brain protein called tau
    accumulates in brain cells in the brainstem
    causing the cells to die.

41
Brain disorders Corticobasal Degeneration (CBD)
  • CBD is a progressive neurological disorder.
  • Initial symptoms begin around age 60.
  • Symptoms Poor coordination, absence of
    movements, impaired balance, abnormal muscle
    postures, cognitive and visual-spatial
    impairments, difficulty in speech, difficulty
    swallowing.
  • Characterized by nerve cell loss and atrophy
    (shrinkage) of multiple areas of the brain
    including the cerebral cortex and the basal
    ganglia.
  • No effective medication.

42
Possible collaborationProblem definition
  • There is an overlap between PSP and CBD (Feany et
    al., 1996), and it would be helpful to
    distinguish these two pathologies.
  • Are they the opposite ends of the same disease?
  • By comparison, CBD is less common, and usually
    displays a more severe cortical atrophy with
    fronto-parietal predominance partly sparing the
    central area.

43
AGING STILL REMAINS AS AN UNSOLVED PROBLEM!
Many Studies Have Shown Contradictory Results
Because Of The Difficulties Of The Problem And
Many Studies Have Evolved In Time With The
Advancements Of The Technologies.
44
CONCLUSION
  • Information from MRI images will not give the
    answers to these questions
  • BUT IT WILL GIVE A CLUE!!!

45
  • THANK YOU!
  • QUESTIONS?
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