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AGING AND ITS EFFECTS ON THE BRAIN

AGING AND ITS EFFECTS ON THE BRAIN. Prepared by: Seniha Esen Yuksel CVIP Lab August 2004. 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?

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AGING AND ITS EFFECTS ON THE BRAIN

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  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. CSF 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. Third ventricle Fourth ventricle 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 1984’s, 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 cont’d: • 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 GM&WM 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 Problems:Partial 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 Problems:Buried 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. Fig:The 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 θ: 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. • Kruggel’s and Zeng’s 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. Figure 10: Regression analysis of fractional brain tissue volume estimates. Models presented indicate the age-related volume estimates throughout adulthood in normal brains. A) %GM B) %WM C) GM/WM ratio 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 one’s 60’s • 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 collaboration:Problem 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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