ABSTRACT
Hemodynamic Changes Reflect Receptor Distributions?...................................... 173
10.1.3. Neurovascular Coupling: Many Neurotransmitters Are Vasoactive..................... 176
10.2. Methodologies ..................................................................................................................... 181
10.2.1. Magnetic Resonance Techniques Used for Collecting Hemodynamic Data ........ 181
10.2.1.1. The Original Technique: First Pass Bolus Mapping of Changes in
rCBV ....................................................................................................... 182
10.2.1.2. CBF-Based Techniques .......................................................................... 182
10.2.1.3. BOLD Techniques .................................................................................. 184
10.2.1.4. IRON CBV Mapping .............................................................................. 185
10.2.2. Advantages and Disadvantages of MR Techniques: Brain-Vein Controversies
Revisited ................................................................................................................. 188
10.2.3. Theoretical Framework for Contrast-to-Noise Ratio............................................. 190
10.2.4. Field Strength Dependencies of BOLD and IRON ............................................... 192
10.2.5. Nonhemodynamic MR Techniques of Potential Use for phMRI.......................... 192
10.2.5.1. Magnetic Resonance Spectroscopy ........................................................ 192
10.2.5.2. Manganese Enhanced MRI..................................................................... 193
10.3. The Confounds of Respiratory Gases and Anesthesia ....................................................... 194
10.4. Basic Drug Challenge Designs ........................................................................................... 197
10.4.1. Acute Model ........................................................................................................... 197
10.4.2. Antagonism and Agonism of Acute Drug Challenges .......................................... 198
10.4.3. The Acute Model for Examining the Effects of Chronic Drug
Administration ........................................................................................................ 199
10.4.4. Pharmacodynamics ................................................................................................. 199
10.4.5. Modeling CBV Changes Induced in the Brain Using a Pharmacologic Model ... 201
10.5. Current Applications of phMRI Techniques ...................................................................... 202
10.5.1. Criteria for Demonstration That the Hemodynamic Effects Are Due to the
Neurotransmitter System in Question .................................................................... 202
10.5.2. Application of the above Criteria to Study the Dopamine System....................... 204
10.5.3. phMRI Studies of Drug Abuse............................................................................... 206
10.5.3.1. Dopaminergic Drugs ............................................................................... 206
10.5.3.2. Nicotine ................................................................................................... 208
10.5.3.3. Heroin...................................................................................................... 208
10.5.4. phMRI Studies of Neurodegeneration ................................................................... 209
10.5.4.1. Rat and Monkey Models of Parkinson’s Disease .................................. 210
Acknowledgments......................................................................................................................... 212
References..................................................................................................................................... 212
The technique of functional magnetic resonance imaging (fMRI) using either relative cerebral
blood volume (rCBV), blood oxygenation level dependent (BOLD) or T
-based cerebral blood flow
(CBF) techniques has led to a revolution in brain mapping [1-3]. This is largely due to the fact that
the advent of a noninvasive tool with reasonable contrast to noise, spatial, and temporal resolution,
allows for studies to be conducted more easily than the prior positron emission tomography (PET)
studies of brain activation. Both fMRI and PET studies of brain activation are based upon the
coupling between neuronal activity, metabolism, and hemodynamics (see also Chapter 11,
Section 2). The possibility that fMRI may help understand the organization and flow of information
in the brain has led to an explosion in the number of centers dedicated to performing the technique.
In addition to the interest in fMRI by the neuroscience community, a number of clinical conditions
has the potential to benefit from the development of fMRI techniques, such as perfusion studies of
stroke, presurgical planning for conservation of eloquent cortex during brain surgery, and
investigation of motor systems in movement disorders. Most fMRI studies have used task
activation, such as photic stimulation or finger movements, or a cognitive challenge to induce
neuronal activity. However, it is also possible to elicit neuronal activity using pharmacologic
ligands. This approach has the potential to generate maps of the metabolic consequences of receptor
stimulation of relevance to a large number of cerebral disorders. Studies of receptor binding can be
performed in vivo using PET imaging, or post mortem with autoradiography. These techniques
allow one to use direct agonists or antagonists to map out the receptor binding parameters or the
density of these sites in the brain. Such studies are of diagnostic value for the examination of
dopamine receptor depletion in Parkinson’s disease (PD) and have great potential for study of
conditions such as drug abuse and schizophrenia.
