COMS 5483

Neuronal Pathways of
Communication
Session 11 Collaborate
Imaging Techniques; Stem Cells; and Aging Brain/Mind/Emotion

June Levitt, Ph.D., LDT, CCC-SLP

 Topics
Ø Review

Ø Brain Imaging Techniques

Ø Stem Cell and its applications

Ø Aging Brain/Mind/Emotions

Ø Summary

Ø In-Class Activity 10

3
 Our plan for today
ü Learn about various brain imaging
techniques.
ü Know the difference between the imaging
techniques that capture the structures and
functions.
ü Gain knowledge about Stem cells and its
applications.
ü Explore the neurological changes with aging
brain.
4
 Topics
Ø Review

Ø Brain Imaging Techniques

Ø Stem Cell and its applications

Ø Aging Brain/Mind/Emotions

Ø Summary

Ø In-Class Activity 10

5
 Neuroimaging Methods

• Structural • Functional
– Computed Tomography – Single photon emission
computed tomography (SPECT)
(CT)
– Positron emission Tomography
– Magnetic resonance (PET)
imaging (MRI)
– Fluorodeoxyglucose position
emission tomography (FDG
• Molecular and PET)
biochemical
– Cerebrospinal fluid (CSF) – Functional magnetic resonance
analyses imaging (fMRI)
– Amyloid PET – Electroencephalography (EEG)
– Diffusion Tensor Imaging – Magnetoencephalography
(DTI)
(MEG)
 Brain Imaging
• Anatomical/Structural brain imaging:
– CT scan (X-ray computed tomography)
takes several cross-sectional X-rays of the brain
that can be stacked to create a 3-D image.

Betts, J. Gordon, et al. (2014). "Anatomy and physiology." (2014): p. 31

 CT Scanner

https://www.medicalnewstoday.com/articles/153201.php
Computed Axial Tomography
(CAT or CT)

https://radiology.ucsf.edu/blog/uncategorized/exploring-the-brain-how-are-brain-images-made-with-ct
UCSF Department of Radiology & Biomedical Imaging: Christopher Hess, MD, Ph.D.
 Brain Imaging

• Anatomical/Structural brain imaging:

– MRI (magnetic resonance imaging)
uses magnetic fields and radio waves to
provide greater detail and superior
imaging.
MRI is less hazardous than radiation, but
more expensive and less available.
 Magnetic Resonance Imaging (MRI)

Axial cut of brain MRI with a left parietal

Betts, J. Gordon, et al. (2014). "Anatomy glioblastoma (malignant tumor)
and physiology." (2014): p. 31
https://www.rsipvision.com/brain-lesion-detection-in-mri-images/
 MRI: Thalamus

https://commons.wikimedia.org/wiki/
File:Thalamus_small.gif

http://cnsvp.stanford.edu/mri/mri-pictures/hypothalamus.jpg
 MRI: Hypothalamus

https://commons.wikimedia.org/wiki/
File:Hypothalamus_small.gif

http://cnsvp.stanford.edu/mri/mri-pictures/hypothalamus.jpg
CT and MRI: side by side
CT MRI
 CT vs. MRI: Radiation

CT Scan MRI
• Radiation dose ranges • MRI machines do not
from 2 to 10 mSv (similar emit ionizing radiation
to the average person’s
exposure from
background radiation in 3
to 5 years.
• Not recommended for
pregnant women or
young children unless
necessary.
 CT vs. MRI: Cost and Time

CT Scan MRI
COST COST
• Range: $1,200 to $3,200 • Range: $1,200 to $4,000

Time to Complete Time to Complete

• Within 5 minutes in total.
• Varies based on the target
Actual scanning is observation.
commonly less than 30 • Range: 10 minutes to 2
seconds. hours (commonly 20 to
90 minutes)
 CT vs. MRI: Imaging and Methods

CT Scan MRI
Images Images
• Shows details about • Shows soft tissue details.
skeletal (bone) structures. Methods
• Claustrophobia is common. It
Methods often causes anxiety, fatigue,
or annoyance over having to
• Seldom creates stay still on a hard table for a
claustrophobia long period of time.
• It makes loud noises.
Headphones are used for
protection from the noises
and to hear instructions
 CT vs. MRI: Limitation for Scanning
CT Scan
• Individuals with metal
implants can get CT scan.
• A person over 450 lbs. may
not fit into the opening of a
conventional CT scanner or
may be over the weight
limit for the moving table.
MRI
• Individuals with Cardiac
Pacemakers, tattoos and
metal implants are
contraindicated due to
possible injury to patient or
image distortion (artifact).
• Individuals over 350 lbs.
may be over table's weight
limit.
 Brain Imaging

• Physiological/Functional brain
imaging:
– PET(positron emission tomography)
detects radioactive emissions from
injected material which is most
commonly used to measure metabolic
activity.
Positron Emission Tomography (PET)
Normal Parkinson’s Disease

https://feinsteinneuroscience.org/about-us-2/research
PET imaging - principles
 Brain Imaging
• Physiological/Functional brain imaging:
– SPECT (single photon emission computed
tomography)
detects radioactive emissions from injected
material; different radioactive materials are
used from the PET and results are less
precise and pictures less detailed, but also
less expensive and therefore more
available.
 Functional imaging:
Single Photon Emission Computed Tomography (SPECT)
SPECT IMAGES – example
 EXAMPLE
One imaging technique shows something the other does not…
CASE: Mild TBI: 4 years post

http://www.cmej.org.za/index.php/cmej/article/view/2805/3140
 PET vs. SPECT
PET SPECT
HIGH (5-7 mm LOWER (12-15
Resolution for Cardiac mm for Cardiac
scanning) scanning)
Isotope that the
Rubidium-82: 75 Technetium-
radiopharmaceutical
seconds 99m: 6 hours
tracer uses
Iterative
Reconstruction Good Improving
(IR) software
Radiation Lower Higher
 Brain Imaging

• Physiological/Functional brain imaging:

– Functional MRI (fMRI)
uses software to take the above
anatomical pictures to create a
visualization of changes in local cerebral
blood flow.
Functional Magnetic Resonance Imaging (fMRI)
 fMRI example:
Grossman, Cooke, DeVita, Alsop, Detre, Chen, & Gee (2001)
 Electroencephalography (EEG)

• Electrodes, placed
on or just under the
scalp, are linked to
an amplifier
connected to a
mechanism that
converts electrical
impulses into
recorded images.
 EEG
• Electrode cap, forms
of data display
 Diffusion Tensor Imaging (DTI)

• An MRI technique that often

used to estimate the axonal
(white matter) of the brain.
• DTI shows microstructural
changes or difference with Tractography image of corona radiata

neuropathology and in healthy subject. Color was used to

label tract termination at cortex (the
color sequence blue to yellow
treatment. corresponds to anterior to posterior
location).

Alexander, Lee, Lazar, & Field (2007)

 Diffuse Optical Tomography (DOT)
• Diffuse Optical Tomography (DOT) and
Imaging (DOI) are non-invasive techniques
that utilize light in the near infrared spectral
region to measure the optical properties of
physiological tissue.
https://www.picoquant.com/applications/category/life-science/diffuse-
optical-tomography-and-imaging#papers

Image: Eggebrecht et al, 2012

 Transcranial Doppler (TCD)/
Transcranial Color Doppler (TCCD)
• Doppler ultrasonography
that measure the velocity
of blood flow through the
brain's blood vessels by
measuring the echoes of
ultrasound waves moving
transcranially (through
the cranium).

https://en.wikipedia.org/wiki/Transcranial_Doppler#/media/File:Transcranial_doppler.jpg
 Cerebral Angiography (CA)
• CA involves the injection of contrast
media into the carotid artery by
means of a catheter.
• Radiographs are taken as the dye
works its way through the cerebral
circulation.
• Angiography may be utilized to
identify bleeding aneurysms,
vasospasm, and some
malformations (Adams HP, et al,
1994. Mohr JP, 199).
http://www.strokecenter.org/professionals/stroke-diagnosis/guide-to-imaging-techniques-in-stroke-diagnosis/cerebral-angiography/
 Magnetic Resonance Angiography (MRA)
• Conventional angiography has
been replaced by magnetic
resonance angiography (MRA)
in some patients with
cerebrovascular disease [Bruno
A, 1993].
• MRA permits the visualization
of blood flow in vessels
without the need for catheters
or contrast agents.

https://en.wikipedia.org/wiki/Magnetic_resonance_angiography
 COMBINED USE
PET and CT
Fused one on the other
CASE: HEAD and NECK cancer
A PET-CT head and neck cancer scan
showing various image
reconstructions. The top left image is
the separate CT scan showing the
anatomy. The top right scan shows the
fused PET and CT scans with false color
added to help interpret the image.
https://www.itnonline.com/article/pet-imaging-101

CASE: Brain Tumor

CT, PET, and CT + PET

http://www.scottdalesupplyonline.com/high-detection-rate-tumours-using-pet-ct-scans-india.htm
 Topics
Ø Review

Ø Brain Imaging Techniques

Ø Stem Cell and its applications

Ø Aging Brain/Mind/Emotions

Ø Summary

Ø In-Class Activity 10

38
 Changing the brain
• Neural plasticity
– Limited neurogenesis: Hippocampus
• Reorganization of the brains
 Changing the Brain
• Neuroplasticity
– Neurogenesis?
– Neural connections
• Invasive example:
– stem cell
• Non-Invasive examples:
– Behavioral methods:
• Constraint-induced therapy
• Lee Silverman Voice Treatment (LSVT)
 Let’s review the Stages of
Cellular & Molecular Processes of Neuronal Development

1. Induction
2. Proliferation
3. Migration
4. Aggregation
5. Differentiation
6. Circuit formation
7. Programmed cell death: loss of extra neurons
 5. CELL DIFFERENTIATION
• Big Question: Where do the different cell
types come from?
• All precursor cells look the same: How do
they differentiate into these many types of
neurons and glia found in the mature brain?
– They are differentiated from one another
by the specific genes and their instructions.
 Invasive example: Stem cell
• A cell that has the ability to continuously
divide and differentiate (develop) into various
other kind(s) of cells/tissues

Caption: This image depicts a colony of human embryonic stem cells grown over a period of 10 months in the absence of mouse feeder
cells. The cell nuclei are stained green; the cell surface in red.
Photo Credit: Courtesy Ren-He Xu/University of Wisconsin
 What are stem cells?
• Unspecialized cells that renew themselves
for long periods through cell division.
• Under certain conditions, they can become
cells with special functions - such as the
cells of the cardiac muscle or the insulin-
producing cells of the pancreas.
 Two types of Stem Cells
Embryonic stem cells Adult-derived stem cells
Began with study of mice, Cells in the human body
sometimes includes human which have remained
embryonic stems cells. undifferentiated.
Derived from very early- Normally only differentiate
stage embryos. They can into the cell types found in
differentiate into any of the that tissue
major cell types.

https://www.quora.com/How-many-cells-are-there-in-the-human-body
 Yamanaka (2006): Induced Pluripotency
New approach to making pluripotent stem cells
• Used transcription factors (chemicals that
turn genes on or off) to induce a normal adult
skin cell to revert back into a pluripotent stem
cell.
• These cells are called “induced pluripotent
stem cells.”

http://sitn.hms.harvard.edu/flash/2014/do-it-yourself-stem-cells-the-story-of-induced-pluripotency/
 Shinya Yamanaka (2006)
Transcription factors

Polk, T.A., 2016

 What are the unique properties of all stem cells?
• Stem cells differ from other kinds of cells in
the body.
• All stem cells—regardless of their source—
have three general properties:
1) they are capable of dividing and
renewing themselves for long periods;
2) they are unspecialized (with/without
limitations); and
3) they can give rise to specialized cell
types.
 Human

https://www.quora.com/How-many-cells-are-there-in-the-human-body
Can stem cells become neurons?

Before Surgery After Surgery

(N Eng J Med 2001;344 (10) p. 710.)
 Regulation
• No federal law ever did ban stem cell research
in the United States, but placed restrictions on
funding and use.
• States interested in providing their own
funding support of embryonic and adult stem
cell research.
– Connecticut, Florida, Illinois,
Massachusetts, Missouri, New Hampshire,
New York, Pennsylvania, Texas, Washington,
and Wisconsin.
Possible Uses of Stem Cell Technology
• Replaceable tissues/organs
• Repair of defective cell types
• Delivery of genetic therapies
• Delivery chemotherapeutic agents
 The first mammal to be cloned
Dolly (1996-2003)

Dolly the sheep on display at the National

Museum of Scotland. Image by Toni
https://askabiologist.asu.edu/content/story-dolly Barros via Wikimedia Commons.
Stem cell treatment: Trials underway
• Cardiac disease
• Diabetes
• Multiple Sclerosis
• Muscular Dystrophy
• Parkinson’s disease
• Spinal cord injury
• Stroke
• Autism
 Future stem cell application
• Alzheimer’s Disease
• Lupus
• Rheumatoid arthritis
• Growing various organs that could be
transplanted, replacing, diseased or
failing organs?
 Stem Cell Research…
• …is advancing knowledge about how an organism
develops from a single cell and how healthy cells
replace damaged cells in adult organisms.

• …is leading scientists to investigate the possibility

of cell-based therapies to treat disease, which is
often referred to as regenerative medicine or
reparative medicine.
 Topics
Ø Review

Ø Brain Imaging Techniques

Ø Stem Cell and its applications

Ø Aging Brain/Mind/Emotions

Ø Summary

Ø In-Class Activity 10

57
 Aging: General changes
• Forgetful
• Distracted easily
• Need extra time to process information
• More susceptible to certain illness:
– Alzheimer’s disease,
– Dementia,
– Stroke,
– Parkinson’s disease…
 Aging: Relatively stable areas

• Learned knowledge

• Memory of knowledge

• Emotional processing
 Aging: Areas generally deteriorate

• Executive function:
– tied to working memory
• Processing speed:
– decline starts in the 20s
• Episodic memories:
– tied to a specific time and place.
– Remembered from a “first-person” perspective.

Park, D. et al., 2000

Anatomical structures
involved in episodic
memory:
a: gyri of the temporal
lobe;
b and c: hippocampal
formation and
entorhinal cortex;
d: frontal lobe.

García-Lázaro et al. (2012)

 Aging: Areas generally intact

• Procedural memory
– Memory for skills and habits
– Muscle memory
• Implicit memories:
– Such as typing on a keyboard, once we become
proficient in typing.
• Semantic memories:
– Knowledge-based (such as vocabulary tasks).

Park, D. et al., 2000

Anatomical structures
involved in semantic
memory:
a, b, and c: frontal,
temporal, and occipital
lobes;
d: Proposed semantic
memory network
within the temporal
lobe, modified from
Patterson et al. (2007).
García-Lázaro et al. (2012)
Aging: Fluid vs. Crystallized intelligence
• Fluid Intelligence
– Relatively independent of what you know.
– Requires ability to think to solve the problems.
– Example: brain teasers and puzzles

• Crystallized Intelligence
– Depend on knowledge, experience, and
acquired skills.
– Example: crossword puzzles
Cattell, R., 1940
 Aging: Emotion
• Older people tend to be more positive than
the younger people.
– Positive emotions are easier to process than
negative emotions?
– Social network becomes smaller as people
age, and they tend to interact with a group
of close friends and family members?
– Life is too short to focus on the negative
side?
 Aging: Depression – Risk of being unnoticed

• Depressed advanced age people tend NOT to

feel sad.
• They tend to:
– Feel de-motivated, hopeless, or empty.
– Unexplained aches and pains.
– Lose interest in socializing and hobbies.
– Anxiety, irritability.
– Slowed movement of speech.
– Memory problems.
 Topics
Ø Review

Ø Brain Imaging Techniques

Ø Stem Cell and its applications

Ø Aging Brain/Mind/Emotions

Ø Summary

Ø In-Class Activity 10

67
 Now we know…
• Imaging techniques:
– Structural
– Functional
• Neural development
– Seven phases
• Stem cell research
– Hope and risk
– Pluripotent vs. Omnipotent
• Areas of the brain that are affected/not affected by
aging
 Topics
Ø Review

Ø Brain Imaging Techniques

Ø Stem Cell and its applications

Ø Aging Brain/Mind/Emotions

Ø Summary

Ø In-Class Activity 10

69