Neuroimaging of Alzheimer’s disease and Healthy Aging BY DR WASIM UNDER THE GUIDANCE OF DR R.K.SOLANKI  ANATOMICAL BRAIN IMAGING CT – cerebral tomography MRI – magnetic resonance imaging FUNCTIONAL BRAIN IMAGING SPECT – single photon emission computed tomography PET – FDG – Positron emission tomography BRAIN CHEMISTRY MEASUREMENT MRS (spectroscopy – NAA/Cr: estimate neuronal volume) BRAIN PATHOLOGY IMAGING FDDNP – neurofibrillary pathology Evolution of Neuroimaging in AD Computed Tomography MRI Volumetric MRI Functional MRI FDG Glucose PET Amyloid Imaging FDG-PET in AD and MCI

1. Neuroimaging of Alzheimer’s
disease and Healthy Aging
BY DR WASIM
UNDER THE GUIDANCE OF
DR R.K.SOLANKI

2. ANATOMICAL BRAIN IMAGING
CT – cerebral tomography
MRI – magnetic resonance imaging
FUNCTIONAL BRAIN IMAGING
SPECT – single photon emission computed tomography
PET – FDG – Positron emission tomography
BRAIN CHEMISTRY MEASUREMENT
MRS (spectroscopy – NAA/Cr: estimate neuronal volume)
BRAIN PATHOLOGY IMAGING
FDDNP – neurofibrillary pathology
BRAIN SCANNING TECHNIQUES

3. Evolution of Neuroimaging in AD
• Computed Tomography
• MRI
• Volumetric MRI
• Functional MRI
• FDG Glucose PET
• Amyloid Imaging
FDG Glucose PET
Lab of Neuro Imaging UCLA School of Medicine. www.loni.ucla.edu/~thompson/AD_4D/dynamic.html.
Helmuth L. Science.
2002;297:1260-1262.
Alzheimer Disease Forum.
http://www.alzforum.org/new/det
ail.asp?id=948.

6. MRI-guided SPECT data: (a) rostral anterior
cingulate (blue), caudal anterior cingulate
(green) and posterior cingulate (red); (b)
temporal horn (purple), hippocampus (blue),
and entorhinal cortex (orange); (c) basal
forebrain (blue) and amygdala (yellow); (d)
banks of the superior temporal sulcus (green).

11. CT Scan
• The initial criteria for CT scan diagnosis of Alzheimer
disease includes diffuse cerebral atrophy with
enlargement of the cortical sulci and increased size
of the ventricles.
• This concept was soon challenged because cerebral
atrophy can be present in elderly and healthy
persons, and some patients with dementia may have
no cerebral atrophy, at least in the early stages.

12. Rate of change of brain atrophy-Changes in the rate of atrophy
progression can be useful in diagnosing Alzheimer disease.
Longitudinal changes in brain size are associated with longitudinal
progression of cognitive loss and enlargement of the third and lateral
ventricles is greater in patients with Alzheimer disease than in control
subjects.
Changes in brain structure-Diffuse cerebral atrophy with widened sulci
and dilatation of the lateral ventricles can be observed.
Disproportionate atrophy of the medial temporal lobe, particularly of
the volume of the hippocampal formations (< 50%), can be seen.

13. • Dilatation of the perihippocampal fissure is a useful radiologic marker
for the initial diagnosis of Alzheimer disease (predictive accuracy of
91%)
• The hippocampal fissure is surrounded laterally by the hippocampus,
superiorly by the dentate gyrus and inferiorly by the subiculum.
• These structures are all involved in the early development of
Alzheimer disease and explain the enlargement in the early stages.

14. • At the medial aspect the fissure communicates with the
ambient cistern and its enlargement on CT scans is often
seen as hippocampal lucency or hypoattenuation in the
temporal area medial to the temporal horn.
• The temporal horns of the lateral ventricles may be
enlarged.
• Prominence of the choroid and hippocampal fissures and
enlargement of the sylvian fissure may be noted.
• White matter attenuation is not a feature of Alzheimer
disease.

15. • Degree of confidence-CT scan indices of hippocampal atrophy
are highly associated with Alzheimer disease but the
specificity is not well established.
• Use of a nonquantitative rating scale showed a sensitivity of
81% and a specificity of 67% in differentiating 21 patients with
Alzheimer disease with moderate dementia from 21 age-
matched control subjects.
• Hippocampal volumes in a sample of similar size permitted
correct classification of 85% of control subjects.

16. • Many studies have shown that cerebral atrophy is significantly
greater in patients with Alzheimer disease than in persons
without it. However, the variability of atrophy in the normal aging
process makes it difficult to use MRI as a definitive diagnostic
technique. Alzheimer disease. Brain image reveals hippocampal
atrophy
MRI

17. Axial, T2-weighted magnetic
resonance imaging (MRI) scan
shows dilated sylvian fissure

18. On structural MRI, atrophy of the entorhinal cortex is already present in
MCI.
MRI measurements of the hippocampus, amygdala, cingulate gyrus,
head of the caudate nucleus, temporal horn, lateral ventricles, third
ventricle and basal forebrain yield a prediction rate of 77% for
conversion to Alzheimer disease from questionable Alzheimer disease.
Functional MRI (fMRI) techniques can be used to measure cerebral
perfusion.

19. • Studies have been performed using MRI with echo-planar imaging
and signal targeting with attenuation radiofrequency (EPISTAR) in
patients with Alzheimer disease.
• Focal areas of hypoperfusion were in the posterior
temporoparietooccipital regions.
• On fMRI paradigms activate a larger area of parietotemporal
association cortex in persons at high risk for Alzheimer disease
than in others.
• The entorhinal cortex activation is relatively low in MCI.

20. Degree of confidence-MRI findings of hippocampal atrophy are highly
associated with Alzheimer disease (Alzheimer's disease), but the
specificity is not well established.
In patients with Alzheimer disease and moderate dementia
hippocampal volumes permitted correct classification in 85% of
patients.
In Alzheimer disease and mild dementia, sensitivity was 77% and
specificity, 80%.
Hippocampal volume was the best discriminator, although a number of
medical temporal-lobe structures were studied, including the amygdala
and the parahippocampal gyrus.

21. Bilateral medial temporal lobe atrophy (right hippocampus illustrated with
arrows) in the same subject with Alzheimer’s disease demonstrated on
coronal images acquired with: (A) 64 detector row computed tomography
scanning; (B) 1.5 tesla MRI volumetric T1 weighted sequence
ANATOMICAL BRAIN IMAGING
CT – cerebral tomography
MRI – magnetic resonance imaging

22. Coronal T1WI of the hippocampus demonstrating progressive atrophy in familial AD

23. NORMAL ALZHEIMER

24. Hippocampus outline Entorhinal Cortex outline

26. PET Scanning-
PET scan with fluorodeoxyglucose used for
1. Early diagnosis
2. Differentiation of Alzheimer disease from other types of dementia.
In Alzheimer's low activity is mostly in the back part (parietal,
posterior temporal and posterior cingulate cortices) of the brain; in
FTD low activity is mostly in the front of the brain.
3. Detection of persons at risk for Alzheimer disease even before the
onset of symptoms

27. It is likely to be caused by a combination of neuronal cell loss and
decreased synaptic activity.
Individuals at high risk for Alzheimer disease (asymptomatic carriers of
the APOE*E4 allele) exhibit a pattern of glucose hypometabolism similar
to that of patients with Alzheimer disease.
PET with ligand PK11195 labeled with11 C showed increased binding in
the entorhinal, temporoparietal and cingulate cortices.
This finding corresponded to the postmortem distribution of Alzheimer
disease pathology
Degree of confidence- PET scanning is more sensitive than SPECT
scanning.
FDG-PET has a sensitivity of 94% and a specificity of 73%.

29. Courtesy of S. Minoshima, University of Washington
FDG-PET in AD and MCI

30. Different amyloid-binding PET scan agents—Pittsburgh Compound-B
and FDDNP ‘’2-(1-(6-[(2-[18F]fluoroethyl)(methyl)amino]-2-
naphthyl)ethylidene)malononitrile’’ amyloid imaging agents may be
useful in the diagnosis of early onset dementia

31. Fibrillar A
Amyloid Imaging with
Positron Emission Tomography (PET)
PET Imaging
Amyloid Plaques

32. Alzheimer’s Disease
Normal Aging (Amyloid Negative)
Normal Aging (Amyloid Positive)
Amyloid PET Imaging in Aging
30% of normal older
people are amyloid
positive

33. Single-photon emission computed tomography- Early SPECT studies of
blood flow replicated findings of functional reductions in the posterior
tempoparietal cortex.
The severity of temporoparietal hypofunction has been correlated with
the severity of dementia in a number of studies.
Reductions of blood flow and oxygen use can be found in the
temporoparietal cortex in patients with Alzheimer disease and
moderate to severe symptoms.
Early reductions of glucose metabolism are seen in the posterior
cingulate cortex.
SPECT

34. Degree of confidence validated SPECT scan studies showing differences
between patients with Alzheimer disease (Alzheimer's disease) and
control subjects reveal high sensitivities and specificities of 80-90%.

35. Magnetic resonance spectroscopy (MRS) is a means
of noninvasive physiologic imaging of the brain that
measures relative levels of various tissue
metabolites
Decrease NAA/Cr
Decrease NAA/ Cho
Increase Myo/NAA

36. MRS in Alzheimer Disease Axial T2-weighted images from an AD patient (L, left) and
a healthy control (R, right). These images show the left elevated NAA, Cr/PCr, Cho
containing compounds, Glu and mI. Most authors have opted for following up AD .

37. Reduced NAA and NAA / Cr (reduction of neuronal population); Increased mI and
mI / Cr (presence of glial repairers phenomena); The reason mI / NAA is considered
the most reliable in the assessment of metabolites in Alzheimer's disease.

38. Magnetic resonance spectroscopy (MRS) in Alzheimer's disease.
•T1W image shows
reduction in the volume of
the hippocampus.
•Proton MRS in
hippocampal region shows
MI peak, decreased NAA
and elevated MI/Cr ratio
•Dx - Alzheimer’s Disease

39. BRAIN PATHOLOGY IMAGING
FDDNP – neurofibrillary pathology

40. FDDNP-PET scans in the parietal region (top) and the temporal region (bottom) in
one control subject and
one subject with mild cognitive impairment who was reclassified on follow-up as
having Alzheimer's disease.
Scans of the subject with mild cognitive impairment, who was reclassified as having
Alzheimer's disease,
showed increased binding in the frontal (8.6%), parietal (8.9%), and lateral temporal
(6.6%) regions.
Red and yellow areas correspond to high FDDNP binding values.

41. Thank You.