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Imaging and Nervous System Development

Imaging and Nervous System Development. Medical imaging How the nervous system develops How the development can malfunction. Imaging Techniques. Key tool in modern research Non- or minimally-invasive/harmful Mostly based on some sort of radiation Can be anatomical or functional.

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Imaging and Nervous System Development

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  1. Imaging and Nervous System Development • Medical imaging • How the nervous system develops • How the development can malfunction

  2. Imaging Techniques • Key tool in modern research • Non- or minimally-invasive/harmful • Mostly based on some sort of radiation • Can be anatomical or functional

  3. Ionizing Radiation

  4. Ionizing Radiation* X-rays CT scans PET SPECT Structural Imaging X-Rays, CT, MRI, (ultrasound) Non-ionizing Radiation MRI fMRI (Ultrasound) Functional Imaging fMRI, PET, SPECT Non-invasive Medical Imaging * Ionizing radiation can change genes or kill cells

  5. X-Rays • The 1st (1895) medical imaging modality. • Good for structural (bone) imaging. • Disadvantages: • Not great at differentiating soft tissues. • X-radiation is ionizing (dangerous). • Images are projections • Many layers are blurred together and cannot be separated. • Image is distorted so accurate measurement cannot be taken. • Not commonly used for brain imaging. 1st X-ray 1895

  6. X-Rays • Areas of high absorption (bone) show up as white in the final X-ray image. • Areas of medium absorption (tissue) show up as gray. • Areas of low absorption (air) show up as black.

  7. Computed Tomography (CT) • Invented in 1972 by Sir Godfrey Hounsfield • Uses X-rays, so ionizing radiation is a still a problem • Also primarily for structural imaging • Two main advantages over X-rays: • CT images are not projections, so each organ, bone and tissue is clearly separated, and measurements are accurate. • The data obtained at each pixel is meaningful.

  8. CT • A number of X-rays are taken from different angles and combined into one computed image by a massive regression analysis. Combined, they form a 3-D representation of the patient.

  9. CT

  10. Magnetic Resonance Imaging (MRI) • fka Nuclear Magnetic Resonance (NMR) • MRI is much better than CT at differentiating tissue types, so it is better for soft-tissue structural imaging. • There are no known harmful effects at reasonable magnetic fields. • MRI studies are more expensive than CT studies.

  11. MRI • Typical MRI: • A large supercooled magnet • Radio emission coils (in the tube) • Radio detection coils (a head coil is shown)

  12. MRI Midline brain view • Acoustic schwannoma • Dr. P’s neoplasm of cranial nerve 8 myelin sheath

  13. Positron Emission Tomography(PET) • Functional imaging – What areas are working? • The brain is fueled by glucose (sugar). Inject a radioactive form of sugar, and see where it is used the most. • Inject patient with radiopharmaceutical, usually 2-deoxyglucose (2-DG) or FDG. • Give the subject a task, and allow some time for it to collect in some place interesting.

  14. Positron Emission Tomography(PET) • The positrons from the radiopharmaceutical annihilate electrons and send 2 photons in opposite directions. • Take a picture of the patient, only counting photons which have counterparts 180 degrees away. • The radioactive pharmaceuticals have very short (1/2 hour) half-lives. • Advantages: • Radiation levels are low and short-lived, therefore relatively harmless to patient.

  15. Positron Emission Tomography(PET) • Disadvantages: • Short half-life means hospital must have an accelerator on-site (very expensive). • A long exposure is required (40 sec) because of low radiation levels. • Low spatial resolution (4 mm) due to annihilation distance. • Images are projections, no anatomical measurements are possible.

  16. PET • Language areas by PET

  17. SPECT • Functional imaging • Single Photon Emission Computed Tomography • The radiopharmaceutical directly emits single 140 KeV gamma photons. • Half-life of about six hours for Tc-99m • Can be manufactured inexpensively off-site • Less versatile and less detailed than PET, but much less expensive.

  18. Functional MRI (fMRI) • Produces images of the increase in O2 flow in the blood to active areas of the brain. Advantages over PET -- • Nothing has to be injected into subject. • Provides both structural and functional info. • Spatial and time resolution are better.

  19. fMRI • Study of speech area activation in bilingual speakers

  20. DTMRI • Diffusion Tensor MRI • Shows pathways • Previously only available by dissection and staining

  21. Development of the NS • DNA holds the master plan • DNA encodes genes • Genetic is not the same as hereditary • There are critical periods for certain steps • Development is unidirectional • Ever increasing complexity • Ever increasing specialization

  22. Development of the NS • Embryonic phase • Sperm penetrates and fertilizes an ovum. • The two haploid genomes merge. • The resulting cell can now undergo mitosis. • Straight mitotic division (no specialization) until about 32 cells (5 generations). • Specialization starts very early.

  23. Development of the NS • Embryonic phase • Differentiation begins shortly after 32 cells. • Ecto-, Meso-, and Endo-derm differentiation • ecto- = surface • meso- = middle • endo- = inside • -derm = skin • Day 15: Formation of a neural streak in the ectoderm.

  24. Development of the NS • Embryonic phase • Day 18: Neural plate thickens on dorsal surface. • Day 19-20: Neural groove forms. • Day 21: Neural groove joins at dorsal center. • Day 22: Neural tube forms, optic groove. • Day 25: Neural tube closes.

  25. Development of the NS • Embryonic phase • Day 28: Neural tube forms 3 swellings: • Prosencephalon (forebrain) • Mesencephalon (midbrain) • Rhombencephalon (hindbrain) • Weeks 3-8: Brain most sensitive to teratogens.

  26. Development of the NS • Embryonic phase • Day 35: Cerebellum starts forming from rhombencephalon. • Weeks 6-18: Cerebrum starts forming from prosencephalon.

  27. Development of the NS • Embryonic phase • Week 12: Limbic system structures form, myelination begins, swallow reflex. • Week 14: Longitudinal and lateral fissures form. • Weeks 16-39: Gyri form. • Week 24: Sucking reflex. • Week 28: Synaptogenesis starts. • Myelination begins before birth, but isn’t finished until about puberty.

  28. Development of the NS • Infant phase • Week 39: Birth – cortex is about 2/3 of brain. • 3 months: Right and left “Broca’s” areas are developing equally fast. Visual neuron myelination completes. • 3-12 months: Right “Broca’s” area grows faster. Gestures and prosody appear. • 12-15 months: Left Broca’s area overtakes right. Speech emerges.

  29. Development of the NS • Infant phase • 9-10 months: Motor neuron myelination completes. Hands start using pincer action, locomotion emerges. Rapid synaptic density increase in frontal lobe. • 2-4 years: Occipital lobe fully developed • 5-6 years: Lateralization complete. Recovery prospects are minimal. • 12-16 years: Frontal lobe fully developed.

  30. Development of the NS • Piaget’s Development Stages • Sensorimotor Stage, 0-2 years • Child changes from a reflexive reactor to an operator, and develops object permanence. • Emergence of language • Myelination of visual, sensory, and motor systems • Rapid frontal lobe synaptic density increase • Preoperational Stage, 2-7 years • Child develops mental representations of objects, and uses words and/or pictures to express these. • Maturation of language, lateralization completes

  31. Development of the NS • Piaget’s Development Stages • Concrete Operational Stage, 7-11 years • Child develops logical thinking • Continued development of frontal lobe • Formal Operational Stage, 11+ years • Child develops abstract thinking • Frontal lobe is close to being mature

  32. Cortical Development • Cortex develops from the inside out. • Neural precursors divide near ventricles. • Immature daughter cells migrate to cortex along radial glia. • Cells specialize in subplate and migrate to their final positions. • Chemo-attractors and –repellants guide neural migration.

  33. Development Pathologies • Causes: • Genetic • Non-46, microdeletions, mutations, Fragile X • Environmental: anoxia, malnutrition, trauma • Toxins: drugs, lead, mercury • Infections: rubella, mumps, flu, CMV, herpes • Metabolic: PKU

  34. Development Pathologies • Embryonic phase critical periods • Dorsal induction phase, 3-4 weeks • Neural tube closure • Ventral induction phase, 5-6 weeks • Major brain segmentation, facial abnormalities • Proliferation phase, 2-4 months • Variations in numbers of neurons • Migration phase, 3-5 months • Anomalous formation of cortex • Organization/Differentiation, 6 mo – 3 years • Synaptic abnormalities • Myelination, 6 mo. – adulthood • Neural conduction

  35. Dorsal Induction Pathologies • Non-closure of neural tube • Always fatal

  36. Dorsal Induction Pathologies • Spina Bifida • “Split spine” • Incomplete closure of inferior end of neural tube • Opening can be microscopic • Rarely fatal

  37. Dorsal Induction Pathologies • Anencephaly • “No brain” • Neural tube fails to close at superior end • Almost always stillborn

  38. Dorsal Induction Pathologies • Encephalo-meningocele • Pouch in brain coverings • Often external

  39. Dorsal Induction Pathologies • Hydrocephalus • Abnormally large ventricles

  40. Ventral Induction Pathologies • Holoprosencephaly • Brain does not divide into two hemispheres • Possible cyclopia

  41. Proliferation Pathologies • Microcephaly • Small head and brain • Smaller number of neurons 13 year old μ Normal 11 year old

  42. Migration Pathologies • Defects at start of neural migration at 11-13 weeks. • Agyria or lissencephaly • No gyri, smooth brain • SX: severe mental retardation, microcephaly & seizures • Pachygyria • “Elephant gyri”, fewer and oversized • SX: spasms, epilepsy, developmental delays

  43. Migration Pathologies • Polymicrogyria • Migrational anomoly at 12-14 weeks. • Many too small gyri • Usually starts at 5-6 weeks, often from a uterine infection. • SX: MR, CP, seizures

  44. Migration Pathologies • Heterotopia • Migrational anomoly at 2-5 months. • White and gray matter are homogenous instead of separated. • Males usually stillborn. • Females generally normal, but with seizures.

  45. Pervasive Developmental Disorders Compulsions • Broad spectrum of disorders: • Autistic Disorder • Asperger’s Disorder • Rett’s Disorder • Childhood Disintegrative Disorder • PDD, NOS • SX Triad: social & language impairments, stereotypical movements. • Related changes in the medial temporal, orbital frontal lobes, & prefrontal cortex. Social Language

  46. Pervasive Developmental Disorders • Autistic Disorder • 1:2500, M = 4xF • MZ = 36-96%, DZ = 0-24% • Onset prior to age 3. • 1. Social impairment. • 2. Impaired verbal and non-verbal communications. • 3. Restricted repetitive and stereotyped behaviors, interests and activities. • Mild to profound MR.

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