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

BRAIN SCANNING TECHNIQUES

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/detail.asp?id=948.

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).

CT Scan

• The initial criteria for CT scan diagnosis of Alzheimerdisease includes diffuse cerebral atrophy withenlargement of the cortical sulci and increased sizeof the ventricles.

• This concept was soon challenged because cerebralatrophy can be present in elderly and healthypersons, and some patients with dementia may haveno cerebral atrophy, at least in the early stages.

Rate of change of brain atrophy-Changes in the rate of atrophyprogression can be useful in diagnosing Alzheimer disease.

Longitudinal changes in brain size are associated with longitudinalprogression of cognitive loss and enlargement of the third and lateralventricles is greater in patients with Alzheimer disease than in controlsubjects.

Changes in brain structure-Diffuse cerebral atrophy with widened sulciand dilatation of the lateral ventricles can be observed.

Disproportionate atrophy of the medial temporal lobe, particularly ofthe volume of the hippocampal formations (< 50%), can be seen.

• Dilatation of the perihippocampal fissure is a useful radiologic markerfor the initial diagnosis of Alzheimer disease (predictive accuracy of91%)

• 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 ofAlzheimer disease and explain the enlargement in the early stages.

• At the medial aspect the fissure communicates with theambient cistern and its enlargement on CT scans is oftenseen as hippocampal lucency or hypoattenuation in thetemporal area medial to the temporal horn.

• The temporal horns of the lateral ventricles may beenlarged.

• Prominence of the choroid and hippocampal fissures andenlargement of the sylvian fissure may be noted.

• White matter attenuation is not a feature of Alzheimerdisease.

• Degree of confidence-CT scan indices of hippocampal atrophyare highly associated with Alzheimer disease but thespecificity is not well established.

• Use of a nonquantitative rating scale showed a sensitivity of81% and a specificity of 67% in differentiating 21 patients withAlzheimer disease with moderate dementia from 21 age-matched control subjects.

• Hippocampal volumes in a sample of similar size permittedcorrect classification of 85% of control subjects.

• Many studies have shown that cerebral atrophy is significantlygreater in patients with Alzheimer disease than in personswithout it. However, the variability of atrophy in the normal agingprocess makes it difficult to use MRI as a definitive diagnostictechnique. Alzheimer disease. Brain image reveals hippocampalatrophy

MRI

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

On structural MRI, atrophy of the entorhinal cortex is already present inMCI.

MRI measurements of the hippocampus, amygdala, cingulate gyrus,head of the caudate nucleus, temporal horn, lateral ventricles, thirdventricle and basal forebrain yield a prediction rate of 77% forconversion to Alzheimer disease from questionable Alzheimer disease.

Functional MRI (fMRI) techniques can be used to measure cerebralperfusion.

• 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 parietotemporalassociation cortex in persons at high risk for Alzheimer disease than in others.

• The entorhinal cortex activation is relatively low in MCI.

Degree of confidence-MRI findings of hippocampal atrophy are highlyassociated with Alzheimer disease (Alzheimer's disease), but thespecificity is not well established.

In patients with Alzheimer disease and moderate dementiahippocampal volumes permitted correct classification in 85% ofpatients.

In Alzheimer disease and mild dementia, sensitivity was 77% andspecificity, 80%.

Hippocampal volume was the best discriminator, although a number ofmedical temporal-lobe structures were studied, including the amygdalaand the parahippocampal gyrus.

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 IMAGINGCT – cerebral tomographyMRI – magnetic resonance imaging

Coronal T1WI of the hippocampus demonstrating progressive atrophy in familial AD

NORMAL ALZHEIMER

Hippocampus outline Entorhinal Cortex outline

PET Scanning-

PET scan with fluorodeoxyglucose used for1. Early diagnosis2. 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; inFTD low activity is mostly in the front of the brain.

3. Detection of persons at risk for Alzheimer disease even before theonset of symptoms

It is likely to be caused by a combination of neuronal cell loss anddecreased synaptic activity.Individuals at high risk for Alzheimer disease (asymptomatic carriers ofthe APOE*E4 allele) exhibit a pattern of glucose hypometabolism similarto that of patients with Alzheimer disease.PET with ligand PK11195 labeled with11 C showed increased binding inthe entorhinal, temporoparietal and cingulate cortices.This finding corresponded to the postmortem distribution of Alzheimerdisease pathology

Degree of confidence- PET scanning is more sensitive than SPECTscanning.

FDG-PET has a sensitivity of 94% and a specificity of 73%.

Courtesy of S. Minoshima, University of Washington

FDG-PET in AD and MCI

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

Fibrillar A

Amyloid Imaging with

Positron Emission Tomography (PET)

PET Imaging

Amyloid Plaques

Alzheimer’s Disease

Normal Aging (Amyloid Negative)

Normal Aging (Amyloid Positive)

Amyloid PET Imaging in Aging

30% of normal older

people are amyloid

positive

Single-photon emission computed tomography- Early SPECT studies ofblood flow replicated findings of functional reductions in the posteriortempoparietal cortex.

The severity of temporoparietal hypofunction has been correlated withthe severity of dementia in a number of studies.

Reductions of blood flow and oxygen use can be found in thetemporoparietal cortex in patients with Alzheimer disease andmoderate to severe symptoms.

Early reductions of glucose metabolism are seen in the posteriorcingulate cortex.

SPECT

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

Magnetic resonance spectroscopy (MRS) is a means of noninvasive physiologic imaging of the brain that

measures relative levels of various tissue metabolites

Decrease NAA/CrDecrease NAA/ ChoIncrease Myo/NAA

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 .

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.

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

BRAIN PATHOLOGY IMAGINGFDDNP – neurofibrillary pathology

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.

Thank You.