Comparative overview of brain perfusion imaging techniques

Numerous imaging techniques have been developed and applied to evaluate brain hemodynamics. Among these are: Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), Xenon-enhanced Computed Tomography (XeCT), Dynamic Perfusion-computed Tomography (PCT), Magnetic Resonance Imaging Dynamic Susceptibility Contrast (DSC), Arterial Spin-Labeling (ASL), and Doppler Ultrasound. These techniques give similar information about brain hemodynamics in the form of parameters such as cerebral blood flow (CBF) or volume (CBV). All of them are used to characterize the same types of pathological conditions. However, each technique has its own advantages and drawbacks. This article addresses the main imaging techniques dedicated to brain hemodynamics. It represents a comparative overview, established by consensus among specialists of the various techniques. For clinicians, this paper should offers a clearer picture of the pros and cons of currently available brain perfusion imaging techniques, and assist them in choosing the proper method in every specific clinical setting.     

Hypofrontality in schizophrenia: a review of the evidence

This paper reviews the possible role of frontal lobe dysfunction in the pathophysiology of schizophrenia. Pathological, computerized axial tomography (CAT) scan and magnetic resonance imaging (MRI) studies have indicated that a substantial number of schizophrenic patients show structural abnormalities in the frontal lobe areas and other parts of the brain. In some cases, these changes can be correlated with negative symptoms. Attempts to study frontal lobe function with neuropsychological tests, topographic EEG, cerebral blood flow (CBF) and positron emission tomography (PET) scans have also indicated that a substantial number of schizophrenics show abnormalities compared to normal controls. However, these abnormalities can be seen to some degree in other conditions. As well, patients early in the course of their illness tend not to show frontal lobe functional abnormalities. The implications of these findings for current theories of schizophrenia are discussed.     

Structural and functional neuroimaging studies of the suicidal brain

Suicidality is a major challenge for today's health care. Evidence suggests that there are differences in cognitive functioning of suicidal patients but the knowledge about the underlying neurobiology is limited. Brain imaging offers the advantage of a non-invasive in vivo direct estimation of detailed brain structure, regional brain functioning and estimation of molecular processes in the brain.We have reviewed the literature on neuroimaging studies of the suicidal brain. This article contains studies on structural imaging such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) and functional imaging, consisting of Positron Emission Tomography (PET), Single Photon Emission Tomography (SPECT) and functional MRI (fMRI). We classified the results of the different imaging modalities in structural and functional imaging.Within our research, we found no significant differences in the suicidal brain demonstrated by Computed Tomography. Magnetic Resonance Imaging studies in subjects with a history of suicide attempt on the other hand deliver differing results, mostly pointing at a higher prevalence of white (especially deep white matter and periventricular) and grey matter hyperintensities in the frontal, temporal and/or parietal lobe and decreased volumes in the frontal and temporal lobe. There seems to be a trend towards findings of reduced grey matter volume in the frontal lobe. Overall, there is no consensus of opinion on structural imaging of the suicidal brain.Research on functional imaging is further divided into studies in resting state, studies in activation conditions and studies on brain neurotransmitters, transporters and receptors.A common finding in functional neuroimaging in resting conditions is a decreased perfusion in the prefrontal cortex of suicidal patients. During cognitive activation, perfusion deficits in the prefrontal cortex have been observed. After fenfluramine challenge, the prefrontal cortex metabolism seems to be inversely correlated to the lethality of previous suicide attempt.The few studies that examined the serotonin transporter in suicide found no significant differences in binding potential. In suicide attempters there seems to be a negative correlation between impulsivity and SERT binding. Our group found a reduced 5-HT_2A binding in the frontal cortex in patients with a recent suicide attempt. The binding index was significantly lower in the deliberate self injury patients compared to the deliberate self poisoning patients.The few authors that examined DAT binding in suicide found no significant DAT differences between patients and controls. However they demonstrated significant negative correlations between DAT binding potential and mental energy among suicide attempters, but not in healthy control subjects. We did not find studies measuring the binding potential of the noradrenalin or gamma amino butyric acid transporter or receptor in suicidal subjects. Several reports have suggested abnormalities of GABA neurotransmission in depression.During our literature search, we have focused on neuroimaging studies in suicidal populations, but in the absence of evidence in the literature on this group or when further collateral evidence is appropriate, this overview expands to results in impulsive aggressive or in depressed subjects.     

D2-receptor imaging with [123I]IBZM and Single Photon Emission Tomography in psychiatry: a survey of current status

Summary D₂-dopamine receptors can be visualized in the human brain in vivo by Single Photon Emission Tomography (SPECT) and the radiolabeled benzamide [¹²³I]IBZM. The present paper reviews the current status of this type of functional brain imaging with respect to basic methodological aspects, data analysis and quantification. The results from published clinical studies in different psychiatric patient populations and normal controls with [¹²³I]IBZM are reviewed. [¹²³I]IBZM-SPECT is a powerful tool for the investigation of D₂-dopamine receptor status in psychiatric disorders, different types of drug treatment as well as therapeutic and side effects of pharmacologic agents. However, there still is a need for standardized imaging times and image-processing procedures. Advantages and disadvantages of SPECT with special regard to Positron Emission Tomography (PET) are also discussed.     

Functional and morphological abnormalities in temporal lobe epilepsy: a comparison of interictal and ictal EEG,CT, MRI,SPECT and PET

Summary Ten patients suffering from drug-resistant complex partial seizures, with EEG abnormalities in the temporal region, were studied by means of non-invasive electrophysiological techniques (video-monitored, 16-channel, prolonged surface and sphenoidal EEG) as well as by imaging techniques (CT, MRI, SPECT and PET). Analysis of interictal and ictal EEG indicated the localization of epileptic activity in one side in eight cases. CT demonstrated focal abnormalities in three, SPECT in five unequivocally (in another four questionably, with the same lateralization as indicated by PET), MRI in eight, and PET in all cases. While only EEG provided specific diagnostic information, the focus definition was consistently good on PET images, poor on CT scans, and generally good but less consistent on MRI.     

Functional neuroimaging strategy in temporal lobe epilepsy: a comparative study of 18FDG-PET and 99mTc-HMPAO-SPECT.

We performed 99mTc-hexamethylpropyleneamineoxime-single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose-positron emission tomography (PET) in 20 epileptic patients with well-lateralized temporal electroencephalographic focus, normal computed tomographic scan, and brain magnetic resonance imaging (MRI) either normal (n = 10) or showing nonspecific changes in the epileptogenic temporal lobe (n = 10). In patients with a normal MRI, PET exhibited focal hypometabolism in 80%, whereas SPECT showed corresponding hypoperfusion in only 20%. In patients with an abnormal MRI, PET and SPECT yielded 100% and 90% sensitivity, respectively. The metabolic and regional cerebral blood flow disturbances were topographically concordant with electroencephalographic and MRI findings in all these patients. Only patients with a large and pronounced hypometabolism on PET images exhibited hypoperfusion on SPECT. Spatial resolution appeared to be the critical factor responsible for the higher sensitivity of PET. However, this superiority of PET did not prove clinically useful in patients whose SPECT was abnormal, particularly when brain MRI showed nonspecific changes in the epileptogenic temporal lobe.     

Asymmetric Neuroimaging in Creutzfeldt-Jakob Disease: A Ruse

Creutzfeldt-Jakob disease (CJD) causes diffuse neurological symptoms, but asymmetric lesions have been found on conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI). Less often, position emission tomography (PET) scanning can also reveal asymmetric lesions in patients with CJD. Such imaging may mislead clinicians. The authors present a case of a woman with CJD who was diagnosed as having suffered a stroke because she had asymmetric T2-weighted imaging (T2WI) MRI abnormalities that were interpreted as a stroke. It was noted that the patient had clinical features consistent with CJD, including rapidly progressive dementia, myoclonus, cerebellar dysfunction, and pyramidal and extrapyramidal signs. This diagnosis was supported by periodic epileptiform discharges on the electroencephalogram (EEG) and by elevated 14-3-3 protein in the cerebrospinal fluid. MRI T2WI and DWI showed dramatically asymmetric abnormalities involving the left cortex. A PET study found decreased metabolism in the left cerebral and right cerebellar hemispheres. The patient's clinical, EEG, and laboratory data were all consistent with CJD, not other diseases, but the MRI and PET had atypical, asymmetric findings. This case demonstrates that CJD should be considered in the differential diagnosis of patients with rapidly progressive neurological decline, even if they have asymmetric imaging findings.     

Brain imaging in functional mental disorders

The application of brain imaging techniques to psychiatry is reviewed with respect to computerized tomography (CT), EEG topography, positron emission tomography (PET), and magnetic resonance imaging (MRI). While early computerized tomography studies have suggested structural abnormalities in schizophrenia, more recent studies have shown that most schizophrenics and patients with other disorders have normal CT scans. EEG topography and positron emission tomography have not been evaluated as fully as computerized tomography. However, preliminary studies indicate some functional abnormalities in schizophrenia and affective disorders compared to normal controls. Magnetic resonance imaging shows promise but has had only a limited application to date in psychiatry.     

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.     

Multi‐modal brain imaging showing brain damage to the orbitofrontal cortex and left hemisphere,in a case of prolonged hypoglycemia‐induced transient hemiplegia followed by persistent encephalopathy

A 21‐year‐old left‐handed male patient was admitted with a 19‐h history of coma after substantial insulin injection for suicide attempt. Although the patient recovered from coma 3 days after injury, he experienced transient hemiplegia followed by permanent brain damage. Electroencephalogram (EEG), brain magnetic resonance imaging (MRI), and brain single‐photon emission computed tomography (SPECT) identified the localization of this dysfunction, but consistency between clinical symptoms and brain images changed depending on the course of treatment. Transient hemiplegia corresponded to abnormal waveforms on EEG and decreased cerebral blood flow on SPECT, whereas persistent dysfunctions corresponded to abnormal brain regions on MRI and SPECT.     

Interictal PET and ictal subtraction SPECT: Sensitivity in the detection of seizure foci in patients with medically intractable epilepsy

Purpose: Interictal positron emission tomography (PET) and ictal subtraction single photon emission computed tomography (SPECT) of the brain have been shown to be valuable tests in the presurgical evaluation of epilepsy. To determine the relative utility of these methods in the localization of seizure foci, we compared interictal PET and ictal subtraction SPECT to subdural and depth electrode recordings in patients with medically intractable epilepsy. Methods: Between 2003 and 2009, clinical information on all patients at our institution undergoing intracranial electroencephalography (EEG) monitoring was charted in a prospectively recorded database. Patients who underwent preoperative interictal PET and ictal subtraction SPECT were selected from this database. Patient characteristics and the findings on preoperative interictal PET and ictal subtraction SPECT were analyzed. Sensitivity of detection of seizure foci for each modality, as compared to intracranial EEG monitoring, was calculated. Key Findings: Fifty‐three patients underwent intracranial EEG monitoring with preoperative interictal PET and ictal subtraction SPECT scans. The average patient age was 32.7 years (median 32 years, range 1–60 years). Twenty‐seven patients had findings of reduced metabolism on interictal PET scan, whereas all 53 patients studied demonstrated a region of relative hyperperfusion on ictal subtraction SPECT suggestive of an epileptogenic zone. Intracranial EEG monitoring identified a single seizure focus in 45 patients, with 39 eventually undergoing resective surgery. Of the 45 patients in whom a seizure focus was localized, PET scan identified the same region in 25 cases (56% sensitivity) and SPECT in 39 cases (87% sensitivity). Intracranial EEG was concordant with at least one study in 41 cases (91%) and both studies in 23 cases (51%). In 16 (80%) of 20 cases where PET did not correlate with intracranial EEG, the SPECT study was concordant. Conversely, PET and intracranial EEG were concordant in two (33%) of the six cases where the SPECT did not demonstrate the seizure focus outlined by intracranial EEG. Thirty‐three patients had surgical resection and >2 years of follow‐up, and 21 of these (64%) had Engel class 1 outcome. No significant effect of imaging concordance on seizure outcome was seen. Significance: Interictal PET and ictal subtraction SPECT studies can provide important information in the preoperative evaluation of medically intractable epilepsy. Of the two studies, ictal subtraction SPECT appears to be the more sensitive. When both studies are used together, however, they can provide complementary information.     

Neuropsychological impairment correlates with hypoperfusion and hypometabolism but not with severity of white matter lesions on MRI in patients with cerebral microangiopathy

BACKGROUND AND PURPOSE: Cerebral microangiopathy, indicated on MRI by lacunar infarctions (LI) and deep white matter lesions (DWML), is said to lead to vascular dementia. METHODS: Fifty-seven patients with proven cerebral microangiopathy were assessed for changes in regional cerebral blood flow (rCBF) and glucose metabolism (rMRGlu) and compared with 19 age-matched controls. The findings were correlated with results of extensive neuropsychological testing, as well as with MRI findings. A special head holder ensured reproducibility of positioning during rCBF (single-photon emission CT [SPECT]), rMRGlu (positron emission tomography [PET]), and MR imaging. White matter and cortex were quantified with regions of interest defined on MRI and superimposed to corresponding PET/SPECT slices. LI and DWML were graded by number and extent. RESULTS: Even with severe DWML and multiple LI, rCBF and rMRGlu values were not reduced. ANOVAs identified brain atrophy and neuropsychological deficits as the main determinants for reduced rCBF and rMRGlu values in both cortex and white matter. Neuropsychological deficits correlated well with decreased rCBF and rMRGlu, whereas MRI patterns such as LI and DWML did not. Factor analysis revealed no correlation of LI and DWML with rCBF, rMRGlu, atrophy, and neuropsychological deficits, showing instead positive correlations between rCBF, rMRGlu, and neuropsychological performance and negative correlations of the latter 3 with brain atrophy. CONCLUSIONS: From these data, we conclude that LI and DWML are epiphenomena that may morphologically characterize cerebral microangiopathy but do not in themselves indicate cognitive impairment. Dementia or neuropsychological deficits, by contrast, are reflected exclusively by functional imaging parameters (rCBF, rMRGlu) and cerebral atrophy.     

Type II focal cortical dysplasia: electroclinical phenotype and surgical outcome related to imaging

Purpose: Type II focal cortical dysplasia (TTFCD), a highly epileptogenic lesion with severe epilepsy curable by surgery, is missed by magnetic resonance imaging (MRI) in about one third of cases. Little is known about the electroclinical presentation in these MRI‐negative patients and a poor surgical outcome is frequently reported. We compared the clinical and neurophysiologic features in MRI‐negative and MRI‐positive cases in order to better identify candidates for surgery. Methods: Among 62 consecutive TTFCD patients (38 male, 24 female; 7–52 years old; 22 children) operated for intractable epilepsy, 25 (40%) presented negative MRI findings. We compared the history of epilepsy; the type, frequency, and distribution of seizures; neurologic examination cognitive and psychiatric impairment; interictal‐ictal electroencephalography (EEG) and stereo‐EEG (SEEG) data, fluorodeoxyglucose positron emission tomography (FDG‐PET) data, neuropathologic findings; and surgical outcome in the MRI‐negative and the MRI‐positive groups. Key Findings: Severe partial epilepsy beginning in childhood, high seizure frequency including status epilepticus, stereotyped seizures suggestive of precise brain localization, extratemporal location and functional area involvement were characteristic and similarly found in both groups. On EEG, pseudorhythmic activity was found in about 40% of patients in each group. SEEG recordings demonstrated the typical pattern characterizing TTFCD in both groups. FDG‐PET had a localization value in 84% of the MRI‐negative cases and helped to delineate the dysplastic cortex in 65% of the MRI‐positive cases. The combination of imaging and neurophysiologic data allowed us to perform safe and restricted resections, limited to a single gyrus in more than half of all cases. In addition, we were able to avoid invasive monitoring in most MRI‐positive cases and even in some selected MRI‐negative cases. The proportion of patients with a favorable surgical outcome was comparable in both groups (88% in MRI‐negative and 94% in MRI‐positive cases). The main difference between the groups was a significantly higher frequency of sleep‐related epilepsy in the MRI‐negative group (p = 0.028). This phenotypic characteristic provides a new argument for TTFCD in MRI‐negative extratemporal epilepsy. Significance: These results lead us to consider that children or adult patients in whom electroclinical data suggest TTFCD, are highly suitable for surgery, especially for cryptogenic sleep‐related epilepsy.     

Presurgical epilepsy localization with interictal cerebral dysfunction

Localization of interictal cerebral dysfunction with 2-[(18)F]fluoro-2-D-deoxyglucose (FDG) positron emission tomography (PET) and neuropsychological examination usefully supplements electroencephalography (EEG) and brain magnetic resonance imaging (MRI) in planning epilepsy surgery. In MRI-negative mesial temporal lobe epilepsy, correlation of temporal lobe hypometabolism with extracranial ictal EEG can support resection without prior intracranial EEG monitoring. In refractory localization-related epilepsies, hypometabolic sites may supplement other data in hypothesizing likely ictal onset zones in order to intracranial electrodes for ictal recording. Prognostication of postoperative seizure freedom with FDG PET appears to have greater positive than negative predictive value. Neuropsychological evaluation is critical to evaluating the potential benefit of epilepsy surgery. Cortical deficits measured with neuropsychometry are limited in lateralizing and localizing value for determination of ictal onset sites, however. Left temporal resection risks iatrogenic verbal memory deficits and dysnomia, and neuropsychological findings are useful in predicting those at greatest risk. Prognostication of cognitive risks with resection at other sites is less satisfactory.     

Brain injury: analysis of imaging modalities.

Advances in imaging have had a significant impact not only on the diagnosis of but also on the management of patients with brain injury. Various modalities are available to image the brain; however, it is not always clear which imaging modality (CT, MRI, SPECT, PET, etc.) is optimal for a specific aspect of traumatized brain. The purpose of this paper is to analyze the over 20,000 imaging studies done in brain injury and to compare the results with the experience in the literature. A detailed comparison has been done relative to CT, MRI, SPECT and PET in traumatic brain injury.     

Interictal hyperemia correlates with epileptogenicity in polymicrogyric cortex

OBJECTIVE: To investigate pathophysiological factors underlying the presence of interictal hyperperfusion within the limits of the polymicrogyric (PMG) cortex in epileptic patients. METHODS: Retrospective observational study on interictal perfusion by Single Photon Emission Computed Tomography (SPECT) in 16 patients with PMG and its correlations with a number of clinical and neurophysiological variables. Patients underwent video-EEG monitoring, neurological and psychiatric assessments, invasive EEG, and the interictal SPECT coregistered to Magnetic Resonance Imaging (MRI). RESULTS: Patients with interictal hyperperfusion within the PMG cortex had a significantly higher spike rate on interictal EEG than patients with normal perfusion. Interictal hyperperfusion was not correlated to sex, age at epilepsy onset, age at evaluation, number of seizures per month, presence of initial precipitating insult (IPI), abnormal neurological examination, EEG findings, ictal semiology, and seizure outcome. The high interictal spike rate did not correlate to a high frequency of seizures per month. CONCLUSIONS: Our work provides further evidences for an intrinsic epileptogenesis of the PMG cortex during the interictal state, which accounts for the major role of PMG tissue in seizure generation. These results might help to increase our understanding about epileptogenesis related to the PMG cortex, providing new tools for more tailored epilepsy surgery in PMG patients.     

Psychomotor disturbances in psychiatric patients as a possible basis for new attempts at differential diagnosis and therapy

Parts I–III of this series established signs of disturbed motor performance-the “psychotic motor syndrome” (PMS) — in schizophrenic and endogenous depressed patients, which was not found in neurotic/reactive depressed nor healthy persons. Part IV yielded EEG signs of concomitant brain dysfunction in these patients, which were demonstrated by other (SPECT/PET) neuroimaging methods also. In part V we engaged in the development of motor-training programs applied both actively and mentally, using the PMS as target syndrome in depressed patients. We hypothesized that motor training would not only improve disturbed motor behaviour, but ameliorate other symptoms of psychopathology additionally, which was supported for these patients. Part VI is the final paper of this series demonstrating favourable results of our motor-training programs in 96 schizophrenic inpatients in two separate investigations. A general discussion to the whole series attempts to link motor symptoms to neuroimaging findings of brain dysfunction during motor challenge and to modern three-and four-factor models of schizophrenic symptomatology. A final version of our complete training programs will be published as an appendix to this paper along with information regarding the abbreviated test battery.     

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.     

Brain SPECT in the pre-surgical evaluation of epileptic patients. Preliminary results.

Pre-surgical evaluation of epileptic patients consists of neurological examination, intensive electroencephalographic (EEG) monitoring and anatomical studies (CT and MRI). Functional methods such as PET and SPECT imaging are now used more frequently. We have studied pre-operatively 15 adult epileptic patients (8 female, 7 male) using a rotational scintillation camera interfaced to a dedicated computer. The tomographic images were obtained 15 minutes after intravenous injection of 99mTc-HMPAO. All had MRI scanning and intensive EEG monitoring which generally included seizure recording. Five patients had progressive lesions (3 meningiomas, 2 astrocytomas). In 10 patients, neuroradiological studies did not show the presence of progressive lesions (2 normal scans and 8 cases with inactive lesions). Two patients with meningioma showed hypoperfusion at the lesion site while the third patient had a marked hyperperfusion which might correlate with the clinical diagnosis of epilepsia partialis continua. In the astrocytoma patients SPECT scans showed hypoperfusion at the lesion site. Data obtained from the 10 patients without progressive CNS lesions showed: (a) in 4, SPECT findings correlated well with the anatomical findings; (b) in 5 instances, SPECT was able to disclose additional functional deficits; (c) in one case, there was no SPECT correlate of a discrete anatomical lesion. In 5 of these cases with no progressive lesions (n = 10) SPECT findings were useful as a complementary tool in determining the clinical or surgical management of these patients. Despite the small number and heterogenicity of the present sample, SPECT seems to be an useful tool as part of the clinical workup of epileptic patients who are candidates for epilepsy surgery.     

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.