Assessing utility of single photon emission computed tomography (SPECT) scan in Alzheimer disease: correlation with cognitive severity

Diagnosis of probable Alzheimer disease (AD) is made by a combination of characteristic clinical findings, when normal laboratory studies reveal no structural or metabolic cause of the dementia. Definite diagnosis of AD, however, can only be made with brain tissue examination. PET scanning reveals parietotemporal decreases in cerebral blood flow (CBF) and glucose metabolism that differentiate AD from normal elderly and from multi-infarct dementia. Preliminary studies suggest that similar defects in CBF are detectable in single photon emission computed tomography (SPECT) in AD. Utilizing the iodinated ligand [123I] HIPDM ([123I] hydroxyiodobenzylpropanediamine), we studied 19 patients with probable AD of varying severity, with emphasis on mild cases, to assess the utility of SPECT as a diagnostic test in AD. Parietotemporal perfusion on SPECT was decreased unilaterally or bilaterally in 16 of 19 AD patients, similar to the defects reported with PET. The degree and extent of decreased CBF on SPECT correlated with AD severity. Strong correlations were obtained between decreases in computer-generated ratios of parietal to cerebellar activity and the level of cognitive function. SPECT was read as normal (on the radiographic film) by the nuclear medicine physician in all cases with Mini-Mental State (MMS) score greater than 24, and showed bilateral parietal perfusion deficits in only 1 of 4 patients with MMS between 22 and 24. Ten of 12 patients with MMS less than or equal to 21 had bilateral parietal abnormalities; the other 2 had unilateral perfusion defects. All patients with MMS less than 15 were bilaterally abnormal. SPECT is less expensive and more widely available than PET, and may have an adjunctive role in diagnosis of AD and other dementias if utilized under the proper circumstances.     

Localized Cerebral Blood Flow Reductions in Patients With Heart Failure: A Study Using 99mTc-HMPAO SPECT

BACKGROUND AND PURPOSE: Reduced resting global cerebral blood flow has been previously detected in association with heart failure (HF), but it is not clear whether there are brain regions that could be specifically affected by those brain perfusion deficits. The authors used a fully automated, voxel-based image analysis method to investigate, across the entire cerebral volume, the presence of resting regional cerebral blood flow (rCBF) abnormalities in HF patients compared to healthy controls. METHODS: rCBF was evaluated with 99mTc-single-photon emission computed tomography in 17 HF patients (New York Heart Association functional class II or III) and 18 elderly healthy volunteers. Voxel-based analyses of rCBF data were conducted using the statistical parametric mapping software. RESULTS: Significant rCBF reductions in HF patients relative to controls (P<.05, corrected for multiple comparisons) were detected in 2 foci, encompassing, respectively, the left and right precuneus and cuneus and the right lateral temporoparietal cortex and posterior cingulated gyrus. In the HF group, there was also a significant direct correlation between the degree of cognitive impairment as assessed using the Cambridge Mental Disorders of the Elderly Examination and rCBF on a voxel cluster involving the right posterior cingulate cortex and precuneus, located closely to the site where between-group rCBF differences had been identified. CONCLUSIONS: These preliminary findings indicate that posterior cortical areas of the brain may be particularly vulnerable to brain perfusion reductions associated with HF and suggest that functional deficits in these regions might be relevant to the pathophysiology of the cognitive impairments presented by HF patients.     

Abnormalities of regional brain metabolism in Alzheimer's disease and their relation to functional impairment

Resting brain metabolism in patients with Alzheimer's disease (AD) has consistently been demonstrated to be reduced. Moreover, the magnitude of the reduction is related to the severity of dementia. Positron emission tomography (PET), which provides regional metabolic rates for glucose in cross-sectional slices of brain, has demonstrated three alterations in AD that are related to functional deficits. First, whole brain metabolic rate is reduced, and these reductions are related to overall severity of dementia. Second, regional metabolic rates in the association cortices demonstrate relatively greater reductions than are observed in the primary sensory and motor cortices, corresponding to marked impairment of higher cognitive function and relative sparing of sensory and motor function. Third, regional metabolic rates in the association cortices demonstrate increased left-right asymmetry relative to controls. Greater metabolic asymmetry is accompanied by disproportionate neuropsychological deficits in either language or visuospatial function, depending on whether the left or right cerebral hemisphere, respectively, has a lower metabolic rate.     

Protein synthesis in the posterior cingulate cortex in Alzheimer's disease

Background: Neuroimaging studies using ¹⁸F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography (FDG‐PET) and single photon emission computed tomography (SPECT) have shown that the posterior cingulate cortex (PCC) is the primary and most prominent area of cerebral metabolic and perfusional decrement in early Alzheimer's disease (AD). We carried out the present preliminary study to investigate whether a decline of cerebral blood flow (CBF) in the PCC in early to moderate AD was accompanied with that of cerebral protein synthesis (CPS). Methods: We carried out both N‐isopropyl‐p‐[123I] iodoamphetamine SPECT (IMP‐SPECT) and L‐[methyl‐11C] methionine positron emission tomography (MET‐PET) in eight AD patients with apolipoprotein E epsilon 4 allele in the early to moderate stage. We also carried out IMP‐SPECT in eight healthy controls (HC). We located 32 regions of interest (ROI), and values of regional MET or IMP uptakes were averaged in five regions; the frontal lobe (FL), the parietal lobe (PL), the medial temporal lobe (MTL), PCC and the occipital lobe. Furthermore, the values in the FL, PL, MTL and PCC were divided by values in the occipital areas, and normalized values of regional CBF (rCBF) and CPS (rCPS) were calculated. Then, the rCBF in the FL, PL, MTL and PCC were compared between AD and HC. In addition, the rCBF and rCPS were compared in the FL, PL, MTL and PCC of AD. Results: The rCBF in the PCC, but not in the other three regions, was significantly lower in AD than in HC. The rCBF was significantly lower than rCPS in the PCC, but rCBF and rCPS were comparable in the other three regions in AD. Conclusions: The CBF reduction in the PCC in AD was partly caused by neuronal loss in the PCC and partly supported the hypothesis that CBF reduction in the PCC was a result of functional deafferentation by neural degeneration in areas other than the PCC.     

Determination of cerebral blood flow by SPECT: a valuable tool in the investigation of dementia?

Positron emission tomography (PET) studies have demonstrated distinctive abnormalities in Alzheimer's disease (AD), multi-infarct-dementia (MID) and Pick's disease. Since PET is a complicated and expensive technique, its clinical application will be limited in the near future. An important finding in these PET studies is persistent coupling of brain metabolism and regional cerebral blood flow (rCBF). Therefore it should be possible to demonstrate bilateral temporoparietal hypometabolism as seen in patients with clinically diagnosed AD indirectly by measuring cerebral blood flow by Single Photon Emission Computer Tomography (SPECT). We report our first experiences with SPECT in the differential diagnosis of dementia with four case histories. We demonstrated temporoparietal hypoperfusion in AD and frontal hypoperfusion in Pick's disease as shown previously by PET. We could not demonstrate a typical SPECT in MID. The main purpose of SPECT in MID could be exclusion of coexisting AD. Based on current knowledge the possibilities and the limitation of this new technique are discussed. It is concluded that rCBF-SPECT may be of value in the diagnosis of AD and Pick's disease. Before this method can be used in daily clinical routine, its diagnostic value should be established according to principles of clinical decision making.     

Neuroimaging as a marker of the onset and progression of Alzheimer's disease

Several neuroimaging techniques are promising tools as early markers of brain pathology in Alzheimer's disease (AD). On structural MRI, atrophy of the entorhinal cortex is present already in mild cognitive impairment (MCI). In the autosomal dominant forms of AD, the rate of atrophy of medial temporal structures separates affected from control persons even 3 years before the clinical onset of cognitive impairment. The elevated annual rate of brain atrophy offers a surrogate tool for the evaluation of newer therapies using smaller samples, thereby saving time and resources. On functional MRI, activation paradigms activate a larger area of parieto-temporal association cortex in persons at higher risk for AD, whereas the entorhinal cortex activation is lesser in MCI. Similar findings have been detected with activation procedures and water (H(2)(15)O) PET. Regional metabolism in the entorhinal cortex, studied with FDG PET, seems to predict normal elderly who will deteriorate to MCI or AD. SPECT shows decreased regional perfusion in limbic areas, both in MCI and AD, but with a lower likelihood ratio than PET. Newer PET compounds allow for the determination in AD of microglial activation, regional deposition of amyloid and the evaluation of enzymatic activity in the brain of AD patients.     

The effects of antipsychotic treatment on cerebral structure and function in schizophrenia

This paper analyses the effects of antipsychotic drug treatment on cerebral structure and function in schizophrenia reviewing qualitatively some of the relevant literature on the issue. Magnetic resonance imaging (MRI) studies of brain morphology in patients at different stages of illness and after varying times of neuroleptic exposure and longitudinal studies show possible different effects of first and second generation antipsychotics. This is true also for functional parameters, such as regional cerebral blood flow and metabolism, analysed, both in resting condition and after specific activation paradigms, with such diverse techniques as positron emission tomography (PET), single photon emission computed tomography (SPECT), functional MRI and MR spectroscopy. The possible molecular mechanisms underlying such differences and whether they represent direct drug effects or indirect consequences of their different and specific interactions with the 'natural' pathophysiological trajectory of brain abnormalities in schizophrenia are matter of present research and debate.     

The effects of antipsychotic treatment on cerebral structure and function in schizophrenia

This paper analyses the effects of antipsychotic drug treatment on cerebral structure and function in schizophrenia reviewing qualitatively some of the relevant literature on the issue. Magnetic resonance imaging (MRI) studies of brain morphology in patients at different stages of illness and after varying times of neuroleptic exposure and longitudinal studies show possible different effects of first and second generation antipsychotics. This is true also for functional parameters, such as regional cerebral blood flow and metabolism, analysed, both in resting condition and after specific activation paradigms, with such diverse techniques as positron emission tomography (PET), single photon emission computed tomography (SPECT), functional MRI and MR spectroscopy. The possible molecular mechanisms underlying such differences and whether they represent direct drug effects or indirect consequences of their different and specific interactions with the ‘natural’ pathophysiological trajectory of brain abnormalities in schizophrenia are matter of present research and debate.     

Spatial patterns of atrophy,hypometabolism, and amyloid deposition in Alzheimer's disease correspond to dissociable functional brain networks

Recent neuroimaging studies of Alzheimer's disease (AD) have emphasized topographical similarities between AD‐related brain changes and a prominent cortical association network called the default‐mode network (DMN). However, the specificity of distinct imaging abnormalities for the DMN compared to other intrinsic connectivity networks (ICNs) of the limbic and heteromodal association cortex has not yet been examined systematically. We assessed regional amyloid load using AV45‐PET, neuronal metabolism using FDG‐PET, and gray matter volume using structural MRI in 473 participants from the Alzheimer's Disease Neuroimaging Initiative, including preclinical, predementia, and clinically manifest AD stages. Complementary region‐of‐interest and voxel‐based analyses were used to assess disease stage‐ and modality‐specific changes within seven principle ICNs of the human brain as defined by a standardized functional connectivity atlas. Amyloid deposition in AD dementia showed a preference for the DMN, but high effect sizes were also observed for other neocortical ICNs, most notably the frontoparietal‐control network. Atrophic changes were most specific for an anterior limbic network, followed by the DMN, whereas other neocortical networks were relatively spared. Hypometabolism appeared to be a mixture of both amyloid‐ and atrophy‐related profiles. Similar patterns of modality‐dependent network specificity were also observed in the predementia and, for amyloid deposition, in the preclinical stage. These quantitative data confirm a high vulnerability of the DMN for multimodal imaging abnormalities in AD. However, rather than being selective for the DMN, imaging abnormalities more generally affect higher order cognitive networks and, importantly, the vulnerability profiles of these networks markedly differ for distinct aspects of AD pathology. Hum Brain Mapp 37:35–53, 2016. © 2015 Wiley Periodicals, Inc.     

Functional imaging of vegetative state applying single photon emission tomography and positron emission tomography

Nuclear medicine techniques, such as single photon emission tomography (SPECT) and positron emission tomography (PET) have been applied in patients in a vegetative state to investigate brain function in a non-invasive manner. Parameters investigated include glucose metabolism, perfusion at rest, variations of regional perfusion after stimulation, and benzodiazepine receptor density. Compared to controls, patients in a vegetative state show a substantial reduction of glucose metabolism and perfusion. While patients post-anoxia exhibit a rather homogenous cortical reduction of glucose metabolism, patients after head trauma often show severe cortical and sub-cortical reductions at the site of primary trauma. To distinguish reduced glucose metabolism due to neuronal inactivation from neuronal loss, flumazenil-PET, an indicator of benzodiazepine receptor density, could add valuable information on the extent of brain damage. Activation studies focus on the evaluation of residual brain network, looking for processing in secondary projection fields. So far the predictive strength concerning possible recovery for the individual patient is limited, and PET and SPECT are not routine procedures in the assessment of patients in a vegetative state.     

Age- and transgene-related changes in regional cerebral metabolism in PSAPP mice

In parallel to imaging studies in humans with Alzheimer's disease (AD), we have mapped brain metabolic activity in transgenic mouse models of AD. Our aim in both is to provide new surrogate markers of progression to help clarify disease mechanisms and rapidly screen candidate therapeutics. Since previous findings of preferential reductions in posterior cingulate glucose metabolism may have been confounded by morphological abnormalities in previously studied "PDAPP" transgenic mice, we first assessed hippocampal and callosal anatomy in PSAPP (PS1xAPP) mice, another transgenic mouse model of AD, and found no major abnormalities. We then used fluorodeoxyglucose (FDG) autoradiography in older and younger PSAPP and wildtype mice to assess the functional state of 56 regions-of-interest across group, age and increasing amyloid load. Reductions in FDG uptake in aged transgenic mice, with significant interactions between group and age, were found in retrosplenial cingulate gyrus, found to be metabolically affected in persons affected by or at risk for AD, and in brain regions known to participate with retrosplenial cingulate in networks contributing to spatial learning deficits found in these animals. Like patients with AD, PSAPP mice have age-related metabolic reductions in posterior cingulate cortex, a finding that does not appear to be related to morphological abnormalities. If longitudinal studies support these progressive and preferential reductions in retrosplenial metabolism in PSAPP mice, these reductions could provide an indicator of disease progression, help bridge the gap between human and animal studies of AD, and aid in clarification of disease mechanisms and screening of promising treatments.     

Future Directions in Imaging Neurodegeneration

Neuroimaging comprises a powerful set of instruments to diagnose various neurodegenerative disorders, clarifies their neurobiology, and monitors their treatment. Magnetic resonance imaging depicts volume changes, as well as abnormalities in functional and structural connectivity. Positron emission tomography (PET) allows for the quantification of regional cerebral metabolism, characteristically altered in Alzheimer’s disease, amyotrophic lateral sclerosis, diffuse Lewy-body disease, and the frontotemporal dementias. PET is also used to measure several neurotransmitters, such as dopamine, which is abnormal in Parkinson’s disease, and to determine the abnormal brain deposition of amyloid-β and tau, as well as brain inflammation. These instruments allow for the quantification in vivo and the longitudinal follow-up of key neurobiological events in neurodegeneration. For instance, amyloid imaging is being used not only to determine who has excess amyloid in the brain but also to investigate whether removing it may slow the deposition of tau and delay cognitive impairment in Alzheimer’s disease.     

Comparison of [99mTc]HMPAO SPECT with [18F]fluoromethane PET in cerebrovascular disease

Positron emission tomography (PET) of [18F]fluoromethane (FM) and single-photon emission tomography (SPECT) of [99mTc]hexamethylpropyleneamine oxime (HMPAO) were performed under identical conditions within 2 h in 22 patients suffering from cerebrovascular disease (8 ischemic infarction, 2 intracerebral hemorrhages, 7 transient ischemic attacks, and 5 multi-infarct syndrome). While gross pathological changes could be seen in the images of either procedure, focal abnormalities corresponding to transient ischemic deficits or to lesions in multi-infarct syndrome and areas of functional deactivation were sometimes missed on SPECT images. Overall, HMPAO SPECT images showed less contrast between high and low activity regions than the FM PET images, and differences between lesions and contralateral regions were less pronounced (6.4 vs 13.3% difference). Regional cerebral blood flow (rCBF) was calculated from FM PET studies in 14 large territorial regions and the pathological lesion, and the regional values relative to mean flow were compared to the relative HMPAO uptake in an identical set of regions defined on the SPECT images. Among individual patients, the Spearman rank-correlation coefficient between relative rCBF and HMPAO uptake varied between 0.48 and 0.89, with a mean of 0.70. While an underestimation of high flow with SPECT--which was demonstrated in a curvilinear relationship between all relative regional PET and SPECT values--could be corrected by linearization taking into account HMPAO efflux from the brain before metabolic trapping, correspondence of SPECT data with PET rCBF values was not improved since this procedure also increased the variance in high flow areas. In the cerebellum, however, a high HMPAO uptake in SPECT always overestimated CBF in relation to forebrain values; this finding might be due to high capillary density in the cerebellum. The differences observed between SPECT and PET data may be explained by technical and physical properties of the methods and by the incomplete first-pass extraction of HMPAO. Additionally, HMPAO or its metabolites may leak through a damaged blood-brain barrier (as observed in one infarct and in the surrounding of hemorrhages), impairing the contrast between lesion and normal tissue. The presented data indicate that the quantification of rCBF by HMPAO SPECT is limited.     

Development of a PET/SPECT agent for amyloid imaging in Alzheimer’s disease

In the search for a cure for Alzheimer’s disease (AD), efforts have been focused on preventing or reversing amyloid deposition in the brain. Efficacy evaluation of these antimyloid therapies would greatly benefit from development of a tool for the in vivo detection and quantitation of amyloid deposits in the brain. Toward this goal, we have developed a series of benzothiazole derivatives as amyloid-imaging agents for positron emission tomography (PET). To extend the potential of these amyloid-imaging agents for routine clinical studies, we also set out to develop iodinated benzothiazole derivatives that could be used as dual agents for either PET or the complementary single photon emission computed tomography (SPECT). Such dual agents would permit PET or SPECT studies using radiotracers with the same chemical identity but labeled with different radionuclides. This would facilitate the validation of clinical SPECT studies, based on quantitative PET studies. In this work we report the synthesis and biological evaluation of a potent, selective, and brain-permeable benzothiazole compound, 2-(3′-iodo-4′-methylaminophenyl)-6-hydroxy-benzothialzole, termed 6-OH-BTA-1-3′-I (4), which can be radiolabeled with either positron-emitting carbon-11 or single photon-emitting iodine-125/iodine-123. The synthesis and radiolabeling of [¹²⁵I]4 or [¹¹C]4 were achieved through direct iodination with sodium [¹²⁵I]iodide in the presence of chloramine T or through radiomethylation with [¹¹C]CH₃I. In vitro amyloid binding assays indicated that [¹²⁵I]4 bound to amyloid deposits in a saturable manner and exhibited affinities in the nanomolar concentration range. Binding studies of [¹²⁵I]4 to postmortem human brain homogenates also showed preference of binding to frontal cortex in the AD homogenates relative to age-matched control homogenates or cerebellum from either AD or control. In vivo pharmacokinetic studies in normal mice following iv injection of [¹¹C]4 indicated that the radioligand entered the brain readily at early time points and cleared from the brain rapidly at later time points with a 2- to 30-min ratio >3. These results suggest that the new radioiodinated benzothiazole ligand might be useful as a surrogate marker for the in vivo quantitation of mayloid deposition in human brain for use with either PET or SPECT.     

Viability of neocortical function shown in behavioral activation state PET studies in Alzheimer disease.

Twenty subjects with mildly to moderately severe Alzheimer disease (AD) and 14 normal elderly control subjects were studied using [18F]fluorodeoxyglucose and positron emission tomography (PET) to investigate regional cerebral glucose metabolism during both a resting state and a behavioral activation state, utilizing a reading memory task (RMT). The RMT produced significant global metabolic activation of 15 +/- 15% in normal subjects and 11 +/- 13% in AD subjects. The occipital regions were preferentially activated, but all regions in both groups were also significantly activated. The RMT did not allow a better discrimination of AD patients from normal controls on the basis of regional metabolic deficits. Regions in the AD group that were individually classified as hypometabolic during rest also exhibited metabolic activation. The apparent viability of hypometabolic regions in AD patients challenges current hypotheses regarding the cause of abnormal metabolism in AD.     

New Techniques in Magnetic Resonance and Epilepsy

Summary: Developments in magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and single photon emission tomography (SPECT) have opened new opportunities for noninvasive brain investigation. Functional imaging methods involving noninvasive MRI and minimally invasive PET and SPECT are available that allow investigation of brain abnormality in intractable epilepsy patients. Noninvasive techniques enable the investigation of many aspects of the underlying neuropathologic basis of intractable seizures and of the relationship of functional abnormalities both to structural abnormalities and to the seizure focus. New MRI techniques demonstrate the structure of the brain in fine detail (especially the hippocampus), provide information about the underlying metabolism of brain regions, and demonstrate functional activity of the brain with high spatial and temporal resolution. The clinical impact of this noninvasive information cannot be overstated and these techniques provide indispensable information to neurologists specializing in epi-leptology. The proper use and interpretation of the findings provided by these new technologies will be a major challenge to epilepsy programs in the next few years.     

Divided attention and metabolic brain dysfunction in mild dementia of the Alzheimer's type

The relationship between reaction time (RT) measures under single-task and dual-task conditions and resting levels of brain metabolism, as measured by positron emission tomography (PET), was examined in patients with mild dementia of the Alzheimer type (DAT) and age- and educationally-matched controls. Slowing of RT in dual-task but not single-task conditions correlated with reductions in brain metabolism in right premotor and right parietal association areas only for the mild DAT patients. The results suggest a relation between divided attention deficits and metabolic dysfunction of right frontal and parietal lobes in mild DAT patients.     

Amyloid load and cerebral atrophy in Alzheimer's disease: an 11C-PIB positron emission tomography study

To determine the relationship between cerebral amyloid plaque load and rates of cerebral atrophy in Alzheimer's disease. (11)C-PIB((11)C-6-OH benzothiazole)PET (positron emission tomography) findings were correlated with volumetric magnetic resonance imaging (MRI) measurements in nine subjects with mild to moderate AD. Analysis revealed a positive correlation between rates of whole brain atrophy and whole brain (p = 0.019) and regional (11)C-PIB uptake. This provides support for the central role of amyloid deposition in the pathogenesis of AD.     

Covarying alterations in Aβ deposition,glucose metabolism,and gray matter volume in cognitively normal elderly

β‐Amyloid (Aβ), a feature of Alzheimer's disease (AD) pathology, may precede reduced glucose metabolism and gray matter (GM) volume and cognitive decline in patients with AD. Accumulation of Aβ, however, has been also reported in cognitively intact older people, although it remains unresolved whether and how Aβ deposition, glucose metabolism, and GM volume relate to one another in cognitively normal elderly. Fifty‐two cognitively normal older adults underwent Pittsburgh Compound B–positron emission tomography (PIB‐PET), [¹⁸F]fluorodeoxyglucose‐PET, and structural magnetic resonance imaging to measure whole‐brain amyloid deposition, glucose metabolism, and GM volume, respectively. Covariance patterns of these measures in association with global amyloid burden measured by PIB index were extracted using principal component analysis–based multivariate methods. Higher global amyloid burden was associated with relative increases of amyloid deposition and glucose metabolism and relative decreases of GM volume in brain regions collectively known as the default mode network including the posterior cingulate/precuneus, lateral parietal cortices, and medial frontal cortex. Relative increases of amyloid deposition and glucose metabolism were also noted in the lateral prefrontal cortices, and relative decreases of GM volume were pronounced in hippocampus. The degree of expression of the topographical patterns of the PIB data was further associated with visual memory performance when controlling for age, sex, and education. The present findings suggest that cognitively normal older adults with greater amyloid deposition are relatively hypermetabolic in frontal and parietal brain regions while undergoing GM volume loss in overlapping brain regions. Hum Brain Mapp 35:297–308, 2014. © 2012 Wiley Periodicals, Inc.     

The Relative Contributions of MRI, SPECT, and PET Imaging in Epilepsy

Summary: Functional and structural neuroimaging techniques are increasingly indispensable in the evaluation of epileptic patients for localization of the epileptic area as well as for understanding pathophysiology, propagation, and neurochemical correlates of chronic epilepsy. Although interictal single photon emission computed tomography (SPECT) imaging of cerebral blood flow is only moderately sensitive, ictal SPECT markedly improves yield. Positron emission tomography (PET) imaging of interictal cerebral metabolism is more sensitive than measurement of blood flow in temporal lobe epilepsy. Furthermore, PET has greater spatial resolution and versatility in that multiple tracers can image various aspects of cerebral function. Interpretation of all types of functional imaging studies is difficult and requires knowledge of time of most recent seizure activity and structural correlates. Only magnetic resonance imaging (MRI) can image the structural changes associated with the underlying epileptic process, and quantitative evidence of hippocampal volume loss has been highly correlated with seizure onset in medial temporal structures. Improved resolution and interpretation have made quantitative MRI more sensitive in temporal lobe epilepsy, as judged by pathology. When judged by electroencephalography (EEG), ictal SPECT and interictal PET have the highest sensitivity and specificity for temporal lobe epilepsy; these neuroimaging techniques have lower sensitivity and higher specificity for extratemporal EEG abnormalities. Regardless of the presence of structural abnormalities, functional imaging by PET or SPECT provides complementary information. Ideally these techniques should be used and interpreted together to improve the localization and understanding of epileptic brain.