Neurological Applications in Diagnosis and Treatment

CEREBROVASCULAR DISEASE

Cerebrovascular disease is the third leading cause of death in the United States. The ability to rapidly diagnose

acute stroke has both therapeutic and prognostic value. Acute intra-arterial thrombolysis of a recently formed thrombus is a new pioneering procedure that may significantly decrease the morbidity and mortality of cerebrovascular disease. PET is able to demonstrate a rise in regional oxygen extraction fraction indicating an evolving stroke. These changes are often demonstrated earlier and show a more extensive tissue damage than what is predicted by CT or MRI. However, work with diffusion-weighted MRI suggests that this may be the most sensitive imaging study for acute stroke. y In patients with reversible ischemic injury there is a decrease in regional cerebral blood flow that is termed misery perfusion. These patients would have a false-positive PET and SPECT scan. Areas of chronic infarction generally demonstrate decreased regional cerebral blood flow and oxygen and glucose metabolism.

SPECT scanning can identify areas of decreased blood flow in patients with acute infarcts that were not seen on CT. A diagnostic test to identify high-risk patients who would benefit from surgical intervention of an arteriosclerotic lesion within the carotid bifurcation would be of great value. A pharmacological stress test with acetazolamide, which causes cerebrovascular dilatation and increased regional cerebral blood flow, has been investigated. y Others have investigated the prognostic value of the ratio of regional cerebral blood flow to regional cerebral blood volume. y The regional cerebral blood volume can be determined with technetium-99m-labeled red blood cells. As the regional cerebral blood flow decreases, the regional cerebral blood volume increases to maintain perfusion. This procedure has been described as an indicator of cerebral perfusion reserve, thus defining a patient's risk for infarction. SPECT and PET have also demonstrated "luxury perfusion," which represents the areas of subacute stroke that receive increased blood flow in relation to the nonaffected brain. This is most likely due to an increase in an aerobic metabolism in the region of infarction. SPECT has also demonstrated hypoperfusion of the contralateral cerebellum in patients with cortical strokes termed crossed cerebellar diaschisis. This is believed to be secondary to disruption of the corticopontine tracts uniquely seen by SPECT.

BRAIN TUMORS

The majority of tumor investigation imaging has been with PET. FDG is the primary positron emitter used today. In general, high-grade neoplasms demonstrate increased metabolism whereas low-grade neoplasms demonstrate relatively decreased activity. There has been high correlation between metabolic activity determined by PET and histological grade of the neoplasm. y , y One of the many uses of PET scanning is to distinguish tumor recurrence from radiation necrosis. Areas of radiation necrosis are diagnosed by focal areas of decreased metabolic activity, whereas tumor recurrence shows increased metabolic activity. PET remains one of the most sensitive tests to differentiate between these two entities.

SPECT has a more limited role in the evaluation of brain tumors. Some enthusiasm has been displayed with the use of SPECT to differentiate a lymphoma from toxoplasmosis in immunocompromised patients. Imaging with thallium-labeled gamma emitters demonstrates increased activity within lymphomas and decreased activity within toxoplasmosis^1 ( ..Fig, 2.3.-2.8.).

DEMENTIA

There have been numerous studies that have described decreased regional glucose metabolism in healthy older subjects within the frontal, parietal, and temporal lobe regions. y Current PET normalizes regional values using internal standards such as the cerebellum or calcarine fissure region.

Within the past decade there has been much excitement about the use of PET and SPECT to evaluate dementia. Alzheimer's disease is the most common cause of dementia

Figure 23-28 A 30-year-old HIV-positive male presents with mental status changed, MR (post-contrast T1W1) demonstrates a focal masslike lesion with ring enhancement within the right frontoparietal area. The primary differential diagnosis is between lymphoma and toxoplasmosisB, Thallium SPECT scan shows abnormal increased uptake representing a primary CNS lymphoma.

in the United States. Characteristic patterns of decreased regional glucose metabolism within the parietal and temporal lobes have been described in patients with AD.y In these patients there is a relative preservation of the calcarine fissure region, sensory motor region, cerebellum, and the basal ganglion region. Decreased metabolic rates for oxygen have also been reported in the same regions that demonstrate areas of decreased glucose metabolism in patients with Alzheimer's disease.^ Patients with progressive Parkinson's disease have a similar pattern, as seen in patients with Alzheimer's disease. Multiple-infarct dementia occurs after multiple lacunar infarctions. PET generally demonstrates multifocal regions of decreased glucose metabolism y that typically correlate to focal lesions demonstrated on CT scans and MR images. A significant decrease in glucose metabolism within the frontal and temporal lobes has been described in patients with Pick's disease. y Patients with Huntington's chorea, a disorder of the extrapyramidal system, have shown a decrease in glucose metabolism within the caudate nuclei. y These findings may present before atrophy of the caudate nuclei demonstrated on CT or MRI.

Decreased regional cerebral blood flow demonstrated with SPECT has shown a similar pattern of decreased glucose metabolism in comparison to PET. Most investigators believe that SPECT is a test of equal sensitivity to characterize dementia.

CEREBRAL TRAUMA

In severe head trauma there is a strong association between a diffuse axonal injury and decreased metabolism within the brain. It has been demonstrated that diffuse and focal areas of decreased metabolism improve over time as a patient recovers from head trauma. Correlations have been found between post-traumatic decreases in glucose metabolism identified by PET and decreased regional cerebral blood flow identified with SPECT. Focal lesions identified on CT demonstrate a larger area of abnormal regional cerebral blood flow by SPECT. y A goal of SPECT research in head trauma has been to use this method to characterize prognosis of focal lesions as well as diffuse axonal injury.

SEIZURE DISORDERS

SPECT and PET have been investigated as complementary noninvasive studies for localization of a seizure focus. CT, MRI, and electroencephalography (EEG) are the primary noninvasive methods used to localize a seizure focus but do not always identify a lesion. These patients quite often require invasive placement of intracerebral depth electrodes. SPECT has demonstrated decreased regional cerebral blood flow within a seizure focus between seizures and increased regional cerebral blood flow ictally. PET studies have shown decreased metabolism between seizures within a seizure focus and increased metabolic activity ictally. In both SPECT and PET, up to approximately 80 percent of patients who demonstrated a focal EEG abnormality also demonstrated an associated perfusion or metabolic activity defect within the same region. y The rapid availability of cyclotron-produced nucleotides is, in general, a limiting factor for the use of PET again for the ictal stage. HMPAO is the SPECT radionucleotide of choice. This tracer is taken up by the brain during the first vascular pass and does not redistribute after the first few minutes. Imaging may be obtained up to 3 to 4 hours after the seizure ictus. There is an additional increased sensitivity if an ictal SPECT scan can be obtained. SPECT has been a major noninvasive imaging modality to help localize a seizure focus. Research suggests that a more stable SPECT imaging agent, ethyl cystinate dimer, which is chemically more stable than HMPAO, will become the radionucleotide of choice.

DEGENERATIVE DISORDERS: PARKINSON'S DISEASE AND HUNTINGTON'S DISEASE

PET can use a number of ligands other than glucose, and these applications are of particular interest in neurological disorders involving neurotransmitter abnormalities. Parkinson's disease and Huntington's disease are the prototypical examples (see Chapter3,4 ) of such conditions, but dystonias and other movement disorders have also been studied with PET. To study the activity of the nigrostriatal dopaminergic system, fluorodopa, a derivative of levodopa, is usually used. Receptor agonists can be used to study postsynaptic function of the same system. Whereas these ligand "probes" remain research tools at the present time, increasing experience may lead to their use in regular clinical neurological practice. In animal models of Parkinson's disease, there is a good correlation between fluorodopa uptake and striatal dopamine content. An even higher correlation exists between uptake and the number of dopamine cells in the substantia nigra zona compacta, the area specifically affected in Parkinson's disease. In patients with severe clinical disability from Parkinson's disease, their fluorodopa scans show lower uptake than those of patients with mild disease. Possible future applications may be the use of such scans in patients with tremors in whom the diagnosis of Parkinson's disease is clinically unclear. It may also prove useful in monitoring the success of such therapies as tissue transplants. In Huntington's disease, most PET attention has focused on its putative utility in preclinical detection and the monitoring of clinical progression.

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