Title: AGING AND ITS EFFECTS ON THE BRAIN
1AGING AND ITS EFFECTS ON THE BRAIN
- Prepared by
- Seniha Esen Yuksel
- CVIP Lab
- August 2004
2Why 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?
3OUTLINE
- Brain basics
- Effects of aging
- Studies
- Diseases
4As 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
5BRAIN 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
6Terms 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
7Ventricles
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
8Ventricles in MRI
9OUTLINE
- Brain basics
- Effects of aging
- Studies
- Diseases
10Evolution 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.
11Evolution 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.
12More 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!
13Why 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.
14What 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
15OUTLINE
- Brain basics
- Effects of aging
- Studies
- Diseases
16Types 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
17Regional 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.
18Regional 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.
19Types 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
20Problems 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
21Segmentation 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
22Segmentation 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).
23Gray 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
24GM 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.
25GM 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.
26GM 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.
27GM 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.
28GM 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.
29Gray 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
30GM 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.
31GM 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.
32Gray 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
33GM 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
34GM 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.
35Gray 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
36Only 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.
37Types 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
38OUTLINE
- Brain basics
- Effects of aging
- Studies
- Diseases
39Brain Disorders / Diseases
- Alzheimer
- Multiple Schlerosis
- Schizophrenia
- Alcoholism and AIDS related dementia
- Corticobasal Degeneration (CBD)
- Progressive Supranuclear Palsy (PSP)
- (possible collaboration with medical school)
40Brain 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.
41Brain 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.
42Possible 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.
43AGING 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.
44CONCLUSION
- Information from MRI images will not give the
answers to these questions - BUT IT WILL GIVE A CLUE!!!
45