0883-2897/91 $3.00 + 0.00 Copyright 0 1991 Pergamon Press plc

Nud. Med. Eiol. Vol. 18, No. 6, pp. 569-582, 1991 Int. J. Radial. Appl. Instrum. Part B Printed in Great Britain. All rights reserved

Positron Emission Tomography in the Investigation of Neuropsychiatric Disorders: Update and Comparison with Magnetic Resonance Imaging and Computerized Tomography WILLIAM

A. WEGENER

and ABASS

ALAVI*

Division of Nuclear Medicine, Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, U.S.A. In many neuropsychiatric disorders, PET imaging offers functional insights unavailable from anatomic imaging alone. Functional deficits may be more extensive than structural findings would indicate, may occur before the detection of anatomic changes, or may even occur in the absence of any structural lesions. We contrast the current role of PET with that of MRI and CT in the investigation of neuropsychiatric disorders including stroke, tumor, head trauma, epilepsy, schizophrenia, movement disorders, normal aging and dementia.

Introduction Over the past two decades, new techniques for imaging brain structure and function have allowed remarkable progress toward the understanding and evaluation of neuropsychiatric disorders. Detailed images of anatomic abnormalities were first provided by computed tomography (CT) and, more recently, by magnetic resonance imaging (MRI). Even in cases of well-demarcated anatomic lesions, such as tumor or trauma, due to disruption of interconnecting neuronal pathways the functional consequences may extend to adjacent and distant brain regions not directly involved. Thus, there is a need to evaluate the global and regional state of the brain function in conjunction with the examination of cerebral structure. In other cases, brain dysfunction may precede anatomic changes or even occur in the absence of any identifiable anatomic lesions. At present, positron emission tomography (PET) is the leading technique for imaging brain function and metabolism in a variety of neuropsychiatric disorders (Jolles et al., 1989). The physical principles underlying PET imaging are simple and relatively straightforward. PET radionuclides emit positrons (positively charged electrons) which travel a short distance before annihilating to

*Author to whom all correspondence and reprint requests should be addressed.

produce two 51 I keV gamma rays. These rays travel in nearly opposite directions (1800 apart) to be detected simultaneously by detectors in a PET scanner encircling the organ of interest. After a large number of such pairwise events are detected, the three-dimensional distribution of a particular positron-labeled radiopharmaceutical may be reconstructed by tomographic techniques similar to those used in CT or MRI. Advances made in PET instrumentation now allow image resolution of the order of 3-5 mm (Muehllehner and Karp, 1986). PET imaging has several important advantages over conventional brain imaging with single photon emitting radionuclides. The excellent spatial resolution achievable with current PET systems surpasses that available on most single photon imaging systems. Detection efficiency is high since collimators are not employed and the high energy 511 keV photons suffer less tissue attenuation. Because of the special nature of dual photon detection, attenuation losses are fully correctable particularly by using transmission measurements. This, in turn, allows accurate quantitation of tracer concentration in the brain. Important physiological and biochemical parameters such as blood flow, metabolic rates, substrate extraction fraction, and receptor density can then be determined using appropriately designed models. Since positron emitters include elements found in living systems, most biologically active compounds can in principle be converted into a radiopharmaceutical 569

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with similar biochemical behavior. Useful PET radioisotropes currently available from medical cyclotrons include 250, 13N, “C and 18F (Fowler and Wolf, 1989). PET is clearly moving into the clinical area (Jolles et al., 1989; Wagner et al., 1988; Jamieson et al., 1988; Alavi et al., 1989). A multitude of scanners are being made with larger field of view and continued improvement in image quality. User-friendly software and display packages can be expected, as well as integrated packages that readily allow cross correlation of functional PET images with anatomic images from MRI or CT. More specific agents, such as receptor imaging agents, will add immense power to PET as brain chemistry can be visualized according to neurotransmitter category. In this update, we will focus on the clinical evaluation of common brain abnormalities with examples taken from our own PET investigations.

Epilepsy PET imaging of brain glucose metabolism using [ i8F]fluorodeoxyglucose (FDG) may play an increasingly important role in studying seizure disorders. Patients with intractable complex partial seizures are candidates for surgical treatment. Partial seizures most frequently arise from a temporal lobe structural lesion. The most common pathology is mesial temporal sclerosis with one or more foci of neuronal loss and gliosis involving the hippocampus, dentate, subiculum and amygdala (Engel et al., 1982a,b). The preoperative localization of the ictal focus includes electroencephalography (EEG), CT, MRI and FDG-PET. Although EEG is essential to the diagnosis and classification of epilepsy, scalp electrodes cannot always differentiate primary cortical activity from that propagated from another site, while stereotactitally implanted depth electrodes are clearly invasive. CT has limited application in the investigation of the temporal lobe because of the presence of bony artifacts. While MRI is very sensitive in the detection of nonsclerotic lesions, it is somewhat insensitive in the detection of sclerotic lesions (Sperling et al., 1986; Fobben et al., 1988). Although MRI is clearly superior for detecting nonsclerotic lesions such as tumors, vascular malformations or tuberous sclerosis, PET appears superior to MRI for detecting seizure foci associated with mesial temporal sclerosis (Sperling et al., 1986). Most PET studies have been performed interictally. The most consistent FDG-PET finding, occurring in about 70% of all patients with partial seizures, is decreased metabolism in the region of the epileptic focus or foci (Fig. 1). The area of interictal hypometabolism is variable, usually extends over the entire temporal lobe, and may include the frontal or parietal lobes, or sometimes the entire ipsilateral hemisphere (Theodore et al., 1983; Engel, 1984).

The extent of FDG-PET abnormality in seizure disorders reflects functional rather than anatomic abnormality. Correlation with histopathology has found the zone of hypometabolism generally larger than the extent of abnormal tissue itself (Engel er al. 1982a). Finally, the hypometabolic zone may become hypermetabolic during a seizure (Engel, 1984). Much remains to be understood about the pathophysiologic and electrophysiologic significance of interictal FDG-PET findings. A recent PET study utilized [ “Clcarfentanil, which has high affinity for mu-opiate receptors, to elucidate the role of opiate receptors and endogenous opioid peptides in complex partial seizures (Frost et al., 1988). Opiate receptor binding was moderately increased in the temporal neocortex on the side of seizure focus, attributed to either increased binding affinity or increased number of unoccupied receptor sites. However, no significant asymmetry of binding was seen in the amygdala or hippocampus, or elsewhere in the brain. Correlative FDG-PET images showed glucose hypometabolism throughout the temporal lobe, including the amygdala and hippocampus, with the decrease directly matching the increased [ “Clcarfentanil binding. The increased activity of the opioid receptor system in the temporal neocortex may represent a tonic anticonvulsant system that limits the spread of seizure activity in the temporal lobe.

Stroke Advances in imaging have clarified the time course of functional and structural changes related to stroke and the pathophysiology of brain ischemia and infarction. CT findings 12-24 h following a stroke frequently include an ill-defined hypodensity with mass effect secondary to edema (Wang et al. 1988). Later on, the affected region may become isodense and then proceed through a stage of contrast enhancement, termed “luxury perfusion”. The end stage of chronic infarction involves a well-defined hypodensity with an enlargement of the adjacent cerebrospinal fluid (CSF) space. MRI has been reported to be more sensitive, showing abnormalities at l-2 h in animal experiments (Spetzler et al., 1983). Typically, there is an area of low signal intensity on Tl-weighted images and high signal intensity on TZweighted images, reflecting increased regional water accumulation due to edema. In the chronic stage, the infarct appears as a cyst-like CSF-space. MRI can also distinctly demonstrate hemorrhagic infarcts, which may be missed on CT. While anatomic imaging provides valuable information about ischemic infarction, PET appears better able to follow the actual sequence of events, particularly in the early stages. PET has been reported to demonstrate abnormalities earlier than CT with metabolic abnormalities often more extensive than would be predicted by either CT or MRI. Also,

Fig. 1. Transaxial interictal FDG-PEG image showing right temporal hypometaholism in a patient with complex partial seizures. (Reproduced with the kind permission of the Journal of Nuclear Medicine.)

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Fig. 2. (A) TZ-weighted MRI image shows region of hyperintensity in the right hemisphere sparing the occipital lobe, and recent hemorrhage in the right frontal lobe. (B) FDG-PET demonstrates marked hypometabolism of the entire right cerebral hemisphere including the occipital lobe, and mild reduction in the left frontal lobe, extending beyond the MRI abnormality. Crossed cerebellar diaschisis is also present. (Reproduced with the kind permission of the Journal of Nuclear Medicine.) 572

Fig. 3. FDG-PET images show a focal hypermetabolic focus in the left thalamus, consistent with a very active tumor. The lack of a surrounding hypometabolism zone suggests the absence of significant edema. (Reproduced with the kind permission of the Journal of Nuclear Medicine.)

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Fig. 4. FDG-PET images of a young patient with schizophrenia. The entire cortex appears to be uniformly afTected by the underlying process resulting in a relative striatal hypermetabolism with increased striatal-to-cortical ratio. (Reproduced with the kind permission of the Journal of Nuclear Medicine.) Fig. 5. FDG-PET study of a normal elderly subject with representative transaxial images from the level of the subcortical structures (upper left) to the cerebellum (lower right). The cortical and subcortical structures are well-delineated and appear relatively symmetric between hemispheres.

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Fig. 6 . (A) MRI image of a moderately early Alzheimer’s disease patient shows significant bilateral tort :ical atropl hy and ventricular enlargement. There are also a few foci of deep white matter hyperintensity. (B) FDG- -PET images show profound bilateral parieto-occipital hypometabolism with additional abnorms tlity in the right temporal lobe. The remainder of the cortical and subcortical structures are relatively int act. 575

Fig. 7. (A) MRf image of a patient with advanced Alzheimer’s disease. There is mild cortical atrophy and moderate ventricular enlargement, with a few foci of deep white matter hyperintensity. These findings are nonspecific and are frequently seen in elderly individuals. (B) Sequential FDG-PET images show marked bilateral parieto-occipital hypometabolism and moderate bilateral fronto-temporal hypometabolism. There is preservation of glucose metabolism in the sensorimotor and calcarine (primary visual) cortices, and in the subcortical nuclei, frequently noted in Alzheimer’s disease. (Reproduced with the kind permission of the Journal of Nuclear Medicine.)

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abnormal metabolic patterns seen on PET have been related to the type of clinical syndrome and to the degree of eventual recovery (Kushner et al., 1987a; Kuhl et al., 1980). PET studies have found that in early infarction, local cerebral blood flow (LCBF) decreases as expected and there is a compensatory rise in the local oxygen extraction fraction (LOEF) (Lassen, 1966). As the stroke evolves to the luxury perfusion stage, LCBF typically increases compared to LOEF. However, diminished LCBF has been reported at this stage in groups of patients with transient ischemic attack and stroke, a finding referred to as “misery perfusion” (Baron et al., 1981b). It remains to be determined if this latter group is at increased risk for infarction (Ackerman et al., 1981; Frackowiak and Wise, 1983). A recent case report describes a patient with a TIA and PET findings of “misery perfusion” who did indeed progress to infarction (Itoh et al., 1988). On PET, a chronic infarct shows diminished LCBF and oxygen/glucose hypometabolism. PET studies show hypometabolic abnormalities distant from the site of infarct (determined from anatomic images), typically occurring in regions which appear normal on CT or MRI (Kuhl et al., 1980; Pappata et al., 1987). These abnormal regions may occur in the ipsilateral or contralateral cerebral hemisphere, or in the contralateral cerebellar hemisphere-a finding termed “crossed cerebellar diaschisis” (Baron et al., 1981a). These findings presumably reflect interruption of neuronal pathways in the brain (Kushner et al., 1987b) and have also been reported in cases of brain tumors and head trauma.

Head Trauma Anatomic imaging has had a dramatic impact upon the diagnosis and management of patients with head trauma. In the acute phase, CT presently remains superior to MRI for detection of subarachnoid hemorrhage, bony fracture, and the differentiation of acute parenchymal hemorrhage from edema (Kelly et al., 1988). However, CT underestimates nonhemorrhagic parenchymal injury. In the subacute and chronic phases, MRI is vastly superior to CT for the detection of intracranial lesions associated with cortical contusion, subcortical gray-matter injury, brain stem injury and diffuse axonal injury (DAI). DA1 most commonly results from shearing stress to white matter tracts, appears multifocal, and carries a poor prognosis (Kelly et al., 1988; Zimmerman et al., 1986). Although MRI is superior to CT for DA1 detection, both techniques appear relatively insensitive to diagnosing these lesions. Also, CT and probably MRI, frequently do not correlate with the degree of neurologic deficit or level of consciousness as assessed by the Glasgow Coma Score (Gentry et al., 1988). PET studies of head trauma are limited to date. FDG-PET cannot distinguish structural lesions from

parenchymal dysfunction, since both appear hypometabolic (LangIitt et al., 1986). Functional changes may extend beyond anatomic lesions seen on CT or MRI, often involving regions adjacent to or remote from the focal damage (Lang&t et al., 1986; Alavi et al., 1987). Cortical contusion, intracranial hematoma and resultant encephalomalacia tend to appear with hypometabolic lesions on PET confined to the associated anatomic lesion seen on CT or MRI. However, subdural and epidural hematomas cause widespread hypometabolism, not infrequently involving the contralateral hemisphere, even when CT and MRI appear unremarkable in these regions (George et al., 1989) (Fig. 2). DA1 may involve widespread cortical hypometabolism as well. The most striking finding in DA1 is profound hypometabolism in the visual cortex (Alavi, 1989a), normally one of the most active regions and usually spared in most neuropsychiatric disorders. Preliminary work from our laboratory suggests that supratentorial lesions in head injury can cause both ipsi- and contralateral cerebellar hypometabolism. Based on comparisons with CT and MRI, approx. 33% of anatomic lesions seen in patients with head injuries were associated with more widespread PET abnormalities and 42% of PET abnormalities had no corresponding anatomic abnormality (Alavi, 1989b). PET-FDG brain activity appears to be a good indicator of functional activity in head injury. Comparison of Glasgow Coma Scale scores versus cerebral (whole brain) glucose metabolic rates showed good correlation in head-injury patients (Alavi, 1989a). Global and regional metabolic rates tend to improve along with clinical recovery (George et al., 1989; Alavi, 1989a). DAI-induced cortical hypometabolism has shown improvement as early as three weeks on serial PET scans (George et al., 1989). Severely injured areas show persistent hypometabolism. There appears to be close correlation of PET with neuropsychologic and language testing in the assessment of site and extent of damage (Rao et al., 1984), although our preliminary data suggest that substantial differences exist between assessment by these approaches.

Oncology CT and more recently MRI are now the principal imaging techniques used to detect and characterize brain tumors. However, cerebral necrosis is a major complication of radiotherapy which neither technique can reliably distinguish from residual tumor recurrence. It appears that FDG-PET imaging is well suited to make this critical distinction. Di Chiro and coworkers (1989) diagnosed radiation necrosis in 10 of 95 patients by noting a focal area of decreased metabolic activity at the involved site. In contrast, tumor recurrence or residual disease appeared as a hypermetabolic focus (Fig. 3). No false positive or false negative diagnoses of radiation necrosis were

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reported, and the method appears able to recognize a tumoral focus among necrotic changes. Valk et al. (1988) studied 34 patients with malignant gliomas treated with interstitial brachytherapy. Using FDG-PET imaging, they also reported that radiation necrosis can be successfully differentiated from tumor recurrence. A surprising discovery was that histologic examination of surgically resected tissue obtained after the PET study in 18 patients found some apparently viable tumor cells among large areas of necrosis. Anatomic imaging has not been able to reliably grade the degree of malignancy or assess prognosis. Utilizing FDG-PET, Alavi et al. (1988) conducted studies on 29 adults with primary brain tumors, of which 72% had had previous treatment. Metabolic rates were elevated in 16 tumors and decreased in 13. Patients with hypermetabolic tumors had median survival times of 7 months from the time of imaging, compared to 33 months for those with hypometabolic lesions. Even among high-grade gliomas, imaging results allowed separation into good and poor prognostic groups. These results suggest that an FDG-PET scan may be a good prognostic indicator and may complement pathologic grading scales for measuring the degree of malignancy. Unlike CT or MRI, PET is the only imaging modality currently able to reliably distinguish radiation necrosis from tumor recurrence. Correlative three-dimensional imaging of CT, MRI and PET may better define target areas for radiation therapy (Schad et al., 1987). Furthermore, PET may provide a unique and invaluable tool for prognostication and management of these patients.

Schizophrenia Imaging studies of brain morphology and function in schizophrenia have yielded abnormal, but often conflicting results. Ventriculomegaly is the most consistent structural abnormality on CT, but this finding occurs with poor specificity and low frequency (340%) (Andreasen, 1988; Pfefferbaum et al., 1988). As with CT, lateral ventricular dilatation has also been noted with MRI (Kelsoe et al., 1988; Rossi et al., 1988) without any consistent accompanying structural abnormality. Although many other abnormalities have been noted on both CT and MRI, they are less frequent and of variable occurrence, possibly attesting to the heterogeneous nature of the disease. In FDG-PET studies of schizophrenia, the two most frequent findings are frontal lobe hypometabolism (Buchsbaum et al., 1982; Farkas et al., 1984; Volkow et al., 1987; Wolkin et al., 1985) and relative preservation of subcortical structural activity compared to decreased cortical metabolism resulting in relative basal ganglia hypermetabolism (Wolkin et al., 1985; Resnick et al., 1988; Gur et al., 1987a) (Fig. 4). Blood flow studies using H2r50 demonstrated increased flow to the left globus pallidus (Early et al.,

1987). Other findings include left hemisphere hypometabolism, temporal lobe hypometabolism (Wolkin et al., 1985), and a normal anterior to posterior gradient. Some of these differing results may reflect different approaches to regional quantification as well as different patient populations and medication histories. It has been reported that short term neuroleptic treatment does not significantly alter the degree of hypofrontality (Wolkin et al., 1985) or the subcortical-to-cortical ratio (Resnick et al., 1988; Gur et al., 1987b), but does increase global metabolism (Wolkin et al., 1985). Hypofrontality in schizophrenia may be related to chronicity of illness or longstanding treatment with medications (Farkas et al., 1984; Volkow et al., 1987). This finding supports the hypothesis of frontal lobe dysfunction (Andreasen, 1988; Wolkin et al., 1985) which results in disruption at the highest level of integrative, adaptive and executive functions. In addition, FDG studies with specific frontal activation tests of sustained attention have demonstrated reduced activation of the frontal lobe (Andreasen 1988; Volkow et al., 1987; Cohen et al., 1988). However, a recent study failed to demonstrate hypofrontality (Kling et al., 1986). The dopamine hypothesis postulates that schizophrenics have overactive dopaminergic mechanisms (Andreasen, 1988). Neuroleptics cause D2 receptor blockage, while amphetamines, which elevate synaptic dopamine levels, exacerbate schizophrenic symptoms. Post-mortem examinations of drug-free or naive patients have shown an excessive number of D2 receptors in the caudate nucleus, putamen, and nucleus accumbens, while Dl receptor numbers remained normal (Owen et al., 1978; Seeman, 1987). PET imaging using receptor-specific agents allows direct visualization in vivo of the dopaminergic system. Two different agents have been used to investigate this phenomenon in schizophrenic patients: “C or ‘“F labeled N-methylspiperone, which irreversibly binds to the D2 receptors, and [ “Clraclopride, which appears to equilibrate rapidly and bind reversibly to D2 receptors. To date, studies on drug-naive schizophrenics have reached different conclusions depending on the agent used (Andreasen et al., 1988). With N-methylspiperone, the number of D2 receptors appeared increased in the basal ganglia (Wong et al., 1986), while normal levels were found with raclopride (Farde et al., 1987). It is possible that raclopride may be more subject to competitive binding from endogenous dopamine which is significantly elevated in actively psychotic schizophrenics (Seeman et al., 1989). If further studies confirm a definite increase in D2 receptors, this will strongly influence future research.

Movement Disorders The most significant PET studies of movement disorders have involved Huntington’s disease and

PET imaging of neuropsychiatric disorders disease. Huntington’s disease (HD) is characterized by progressive chorea and dementia following midlife onset. CT and MRI studies show no abnormality early on, but after several years of progression of the disease, both reveal a marked loss of volume in the caudate nucleus and putamen (Kuhl et al., 1982; Lukes et al., 1983). FDG-PET studies have revealed significant caudate and putamen hypometabolism in early HD before structural atrophy has appeared (Mazziotta et al., 1987; Young et al., 1987). Although controversial, some studies suggest that PET may be able to detect asymptomatic HD carriers and may indicate the onset of symptoms at a future date (Mazziotta et al., 1987; Kuhl, 1984b; Hayden, 1987). Regardless of disease severity, duration or medications, HD subjects show normal global and local cortical metabolism (Kuhl et af., 1984b). These PET results which show abnormalities confined to the subcortical nuclei in HD are in contrast to the global cortical dysfunction evident in dementia due to Alzheimer’s disease even in early stages of disease. Parkinson’s disease (PD) is characterized by bradykinesia, tremor and rigidity with 20-30% of patients progressing to dementia. PD occurs with a loss of dopaminergic neurons in the substantia nigra and locus coerulus. CT plays little role in diagnosing PD, while the major finding on MRI appears to be decreased width of substantia nigra (Braffman et al., 1989). FDG-PET studies have shown conflicting results in the striatum, which may reflect the degree of upregulation as the disease progresses (Kuhl et al., 1984a,b; Rougemont et al., 1986). Levodopa therapy does not affect local or global metabolic rates, despite significant clinical improvement. In general, there is also a mild, uniform decreased cerebral metabolism, the cause of which remains unclear. This uniform hypometabolism is unrelated to disease duration but worsens with the development of dementia and, in severe cases, may be indistinguishable from the appearance of Alzheimer’s disease on FDG-PET (Rougemont et al., 1986). In vivo neurotransmitter studies should aid in further understanding and the assessment of response to therapy. These studies are underway in several centres at this time.

Parkinson’s

Normal Aging and Dementia Changes that accompany aging have been extensively investigated. Pathologic studies in the normal elderly population reveal regional neuron loss in the frontal, parietal and temporal lobes (Brody, 1955; Tomlinson et al., 1968; Anderson et al., 1983). Generalized ventricular enlargement and cortical sulcal atrophy are typical .anatom.ic findings. Common white matter abnormalities include periventricular and/or focal deep white matter hyperintensities on MRI or hypodensities on CT. Most studies report that these white matter changes increase with aging and may represent ischemia or infarct, with hyper-

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tension often an underlying condition (Braffman et al., 1988; Drayer, 1988). However, since such changes have been found in subjects without hypertension or other identifiable vascular risk factors, the actual pathologic mechanism may be multifactorial. Our preliminary data suggest that deep white matter lesions noted in normal aging do not significantly affect regional or global metabolic rates. PET findings in normal aging remain somewhat controversial. Several reports indicate that there is no significant decrease in whole brain glucose metabolism using FDG (Dura et al., 1983; de Leon et al., 1985; Alavi, 1989a) although other reports show a decline (Dastur, 1985; Kuhl et al., 1982). In contrast, most investigators have reported diminished regional glucose metabolism in healthy elderly subjects in the temporal, parietal, somatosensory and especially the frontal regions (Kuhl et al., 1982; Chawluk, 1987b, 1985; De Leon et al., 1987; Alavi et al., 1986) (Fig. 5). Metabolic rates in the posterior structures, particularly in the calcarine cortex, appear well preserved (Chawluk, 1985; Alavi et al., 1986). Anatomic and functional changes that occur with dementia have been extensively studied using imaging techniques. Alzheimer’s disease (AD) is the most common cause of dementia and accounts for more than half of the cases. Other causes include multiple infarctions (multi-infarct dementia; MID), combined AD and MID, and less common etiologies such as normal pressure hydrocephalus, mass lesions, infections, AIDS and metabolic/nutritional disorders (Beck et al., 1982; Jellinger, 1976; Ho et al.. 1985; Tomlinson et al., 1970). In AD, ventricular and cortical sulcal enlargement appears greater than that seen in normal aging. However, these findings are nonspecific and may occur in other dementias. Focal temporal lobe atrophy with enlargement of the surrounding cerebrospinal fluid (CSF) space has been described in AD patients using CT (George et al., 1987). This finding appears to be the only reported anatomic imaging abnormality which is said to distinguish AD from normal aging with an 80-90% accuracy. Although controversial, the data suggest that AD patients cannot be reliably distinguished from normal elderly controls by the number of focal deep white matter lesions. However, the presence of periventricular hyperintensity (PVH) on MRI might aid in making such a distinction (Fazekas et al., 1987): normal elderly subjects have normal caps, pencil-thin or absent PVH, while MID patients show extensive focal and confluent white matter abnormalities, associated with “classical” infarcts. The diagnostic significance of these findings remains to be clarified. FDG-PET studies appear particularly promising in the evaluation of dementias, with characteristic patterns having been reported in several types of disorders (Jamieson et al., 1988; Alavi, 1989a). In AD patients, diminished regional glucose metabolism has been described in the parietal and temporal lobes; the

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frontal lobes may also demonstrate hypometabolic changes, particularly in severe cases (Figs 6 and 7). Relatively preserved glucose metabolism has been noted in the primary visual and sensorimotor cortices, as well as the cerebellum. The visual cortex glucose metabolism especially remains stable during different stages of AD. Global and regional cerebral metabolic rate for oxygen (CMRO?) decreases, particularly in the temporal and parietal regions, have been reported in AD; substantially diminished CMROz has been noted in severe cases. An associated CBF decrease has also been reported (Frackowiak et al., 198la,b). AD patients with progressive decrease in glucose metabolism have been shown to display corresponding cognitive loss (Jamieson et al., 1987). Hemispheric asymmetry may also be present, with more severe hypometabolism on the left compared to the right (Alavi, 1989a). This finding may explain the language difficulties seen in certain advanced AD patients. PET may distinguish other types of dementia from AD. MID patients tend to exhibit scattered focal regions of diminished glucose metabolism, instead of the predominantly parietal and temporal hypometabolism seen in AD (Benson et al., 1983). This pattern, along with characteristic multiple lesions particularly in white matter seen on MRI, is usually sufficient to establish the diagnosis of MID. Reports of individuals with Pick’s disease indicate a more profound glucose hypometabolism in the frontal regions than in the temporal and parietal regions (Kamo et al., 1987). Although a number of controversies exist, studies to date demonstrate a potential for PET to characterize and further the understanding of dementing disorders. A standardized method for quantification of metabolic data remains to be established, while the need for atrophy correction of metabolic rates is being addressed (Chawluk et al., 1987a). Selective stimulation/activation studies may also provide greater sensitivity by enhancing the contrast between the sites of involvement compared to relatively spared regions.

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