Bioimaging in Neurodegeneration.pdf
Bioimaging in Neurodegeneration.pdf
BIOIMAGING IN NEURODEGENERATION
EDITED BY
PATRICIA A. BRODERICK, PhD
Department of Physiology and Pharmacology,
City University of New York Medical School;
Department of Neurology, New York University
School of Medicine; NYU Comprehensive
Epilepsy Center,New York, NY
DAVID N. RAHNI, PhD
Department of Chemistry and Physical Sciences
Pace University, Pleasantville, NY
EDWIN H. KOLODNY, MD
Department of Neurology
New York University School of Medicine
New York, NY
BIOIMAGING IN
NEURODEGENERATION
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Cover design by Patricia F. Cleary.
Cover illustrations: FOREGROUND, TOP: (left) Transaxial slice at the level of the striatum showing uptake of 99m Tc-TRODAT-1 in dopamine
transporters in a normal healthy volunteer; (right) a patient with hemi-PD exhibits a unilateral decrease in the uptake of 99m Tc-TRODAT-1 in
the side contralateral to clinical symptoms, most severely in the putamen (Chapter 2, Figs. 1 and 3; see full captions and discussion on p. 15.)
FOREGROUND, MIDDLE: Regional NAA/Cr decrease in AD (Chapter 9, Fig. 2; see complete caption on p. 98 and discussion on p. 96). FOREGROUND,
BOTTOM: Proton MRS (TE = 144 ms) in Canavan’s disease demonstrating marked elevation in NAA caused by aspartoacylase deficiency (Chapter
21, Fig. 11; see full caption on p. 253 and discussion on p. 251). BACKGROUND: Hippocampal and entorhinal cortex boundary definition (Chapter
9, Fig. 1; see full caption on p. 97 and discussion on p. 96).
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eISBN 1-59259-888-9
Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1
Library of Congress Cataloging-in-Publication Data
Bioimaging in neurodegeneration / edited by Patricia A. Broderick, David N.
Rahni, Edwin H. Kolodny.
p. cm.
Includes bibliographical references and index.
ISBN 1-58829-391-2 (alk. paper)
1. Brain--Degeneration--Imaging. I. Broderick, Patricia A., 1949- II.
Rahni, David N. III. Kolodny, Edwin H.
RC394.D35B55 2005
616.8'04757--dc22
2004026624
v
Preface
Bioimaging is in the forefront of medicine for the diagnosis and
treatment of neurodegenerative disease. Conventional magnetic
resonance imaging (MRI) uses interactive external magnetic fields
and resonant frequencies of protons from water molecules.
However, newer sequences, such as magnetization-prepared rapid
acquisition gradient echo (MPRAGE), are able to seek higher
levels of anatomic resolution by allowing more rapid temporal
imaging. Magnetic resonance spectroscopy (MRS) images
metabolic changes, enabling underlying pathophysiologic
dysfunction in neurodegeneration to be deciphered. Neuro-
chemicals visible with proton 1H MRS include N-acetyl aspartate
(NAA), creatine/phosphocreatine (Cr), and choline (Cho); NAA
is considered to act as an in vivo marker for neuronal loss and/or
neuronal dysfunction. By extending imaging to the study of
elements such as iron—elevated in several neurodegenerative
diseases—laser microprobe studies have become extremely
useful, followed by X-ray absorption fine-structure experiments.
Positron emission tomography (PET) and single-photon emission
tomography (SPECT) have become important tools in the differential
diagnosis of neurodegenerative diseases by allowing imaging of
metabolism and cerebral blood flow. PET studies of cerebral
glucose metabolism use the glucose analog [18F] fluorodeoxyglucose
analog ([18F]FDG) and radioactive water (H215O) and SPECT
tracers use 99mTc-hexamethylpropylene amine oxime, (99mTc-
HMPAO), and 99mTc-ethylcysteinate dimer (99mTc-ECD).
Moreover, direct imaging of the nigrostriatal pathway with 6-[18F]-
fluoro-1-3,4-dihydroxyphenylalanine (FDOPA) in combination
with PET technology, may be more effective at differentiating
neurodegenerative diseases than PET or SPECT alone.
Radioactive cocaine and the tropane analogs directly measure
dopamine (DA) transporter binding sites and 99mTc-TRODAT-1
is a new tracer that could move imaging of the DA neuronal
circuitry from the research environment to the clinic. [123I]
altropane SPECT may equal and further advance FDOPA PET.
Surgical treatments of neurodegenerative diseases are gaining
attention as craniotomies become more routine, and as patients opt
for surgery because they experience intractable responses to
pharmacotherapy for neurodegeneration. These treatments fall into
three categories: lesion ablation, deep brain stimulation (DBS),
and restorative therapies such as nerve growth factor infusion or
DA cell transplantation along the nigrostriatal pathway,
particularly in Parkinson’s disease. Also, electron micrographics
image amyloid β aggregation in Alzheimer’s disease (AD) and
MRI (gadolinium enhanced) has been successfully exploited to
image neuroinflammation in AD. MR-based volumetric imaging
helps to predict the progression of AD via mild cognitive
impairment (MCI) studies.
Novel neuroimaging technologies, such as neuromolecular
imaging (NMI) with a series of newly developed BRODERICK
PROBE® sensors, directly image neurotransmitters, precursors,
and metabolites in vivo, in real time and within seconds, at separate
and selective waveform potentials. NMI, which uses an
electrochemical basis for detection, enables the differentiation of
neurodegenerative diseases in patients who present with mesial
versus neocortical temporal lobe epilepsy. In fact, NMI has some
remarkable similarities to MRI insofar as there is technological
dependence on electron and proton transfer, respectively, and
further dependence is seen in both NMI and MRI on tissue
composition such as lipids. NMI has already been joined with
electrophysiological (EEG) and electromyographic (EMG) studies
to enhance detection capabilities; the integration of NMI with
MRI, PET, and SPECT can be envisioned as the next advance.
The tracer molecule, [11C] α-methyl-L-tryptophan (AMT) is
already used with PET to study serotonin (5-HT) deficiencies,
presumably attributable to kynurenine enhancement in neocortical
epilepsy patients. Moreover, AMT PET, in addition to FDG PET,
provides reliable diagnosis for pediatric epilepsy syndromes such
as West’s syndrome. Important in children with cortical dysplasia
(CD), FDG PET delineates areas of altered glucose, which can be
missed by MRI. The new tracer, [11C] flumazenil used with PET
(FMZ PET), has found utility in the detection of epileptic foci in
CD patients with partial epilepsies, and yet normal structural
imaging is observed. Another new 5-HT1A tracer for PET imaging
in abnormal dysplastic tissue is a carboxamide compound called
[18F]FCWAY.
Diagnosis of neocortical epilepsy has been significantly
advanced by IOS or intrinsic optical signal imaging. IOS has its
basis in the light absorption properties of electrophysiologically
active neural tissue, activity caused by focal alterations in blood
flow, oxygenation of hemoglobin, and scattering of light. IOS can
map interictal spikes, onsets and offsets, and horizontal
propagation lines. Thus, IOS is useful for diagnosing “spreading
epileptiform depression.” As with NMI, IOS holds promise for
intraoperative cortical mapping wherein ictal and interictal
margins can be more clearly defined. As does intraoperative MRI
(iMRI) with neuronavigation, these technologies provide what is
called “guided neurosurgery.” Correlative imaging of general
inhalational anesthetics such as nitrous oxide (N2O) during
intraoperative surgery is made possible by NMI technologies with
nano- and microsensors.
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