AGING AND ITS EFFECTS ON THE BRAIN

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AGING AND ITS EFFECTS ON THE BRAIN

• Prepared by
• Seniha Esen Yuksel
• CVIP Lab
• August 2004

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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?

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OUTLINE

• Brain basics
• Effects of aging
• Studies
• Diseases

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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

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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

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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
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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
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Ventricles in MRI
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OUTLINE

• Brain basics
• Effects of aging
• Studies
• Diseases

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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.

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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.

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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!

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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.

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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

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OUTLINE

• Brain basics
• Effects of aging
• Studies
• Diseases

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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

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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.

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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.

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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

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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

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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
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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).

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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

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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.

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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.
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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.
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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.

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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.
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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

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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.
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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.

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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

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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
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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.

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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

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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.

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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

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OUTLINE

• Brain basics
• Effects of aging
• Studies
• Diseases

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Brain Disorders / Diseases

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

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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.

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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.

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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.

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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.
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CONCLUSION

• Information from MRI images will not give the
  answers to these questions
• BUT IT WILL GIVE A CLUE!!!

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• THANK YOU!
• QUESTIONS?