Surgical target selection in cerebral glioma surgery: linking methionine (MET) PET image fusion and neuronavigation.

OBJECTIVE: The objective of this study was to investigate the histological correlate of (11)C-methionine (MET) PET uptake of brain gliomas by image fusion for navigated surgery. METHODS: Twenty-seven patients (18 male, 9 female; mean age 42 years; range 11-77 years; 8 low-grade and 11 high-grade astrocytomas or mixed gliomas, 8 oligodendrogliomas) underwent MET PET studies preoperatively. RESULTS: MET PET tumor uptake was detected in 26 of 27 patients (96.3%). The quantitative MET tumor standardized uptake value (SUV) ratio was significantly higher in malignant gliomas and oligodendrogliomas than in low-grade gliomas (2.76/2.62 vs. 1.67, p=0.03). Generally, qualitative visual grading of MET uptake revealed 2 main patterns: focal MET uptake in 12 and uniform global MET uptake in 11 patients. Focal uptake corresponded to malignant glioma histology in 66.7%, and uniform global uptake to oligodendroglial histology in 72.7%. In oligodendrogliomas, global MET uptake constituted 81.5% (range 53.8-135%) of the MRI T(1) tumor volume on average and was limited to the MRI FLAIR tumor volume in 86% (7/8) of patients. Tissue samples of focal MET uptake areas correlated with histological anaplasia in 66.6% (8/12 glioma patients), although 62.5% (5/8 patients) lacked MRI contrast enhancement. CONCLUSION: MET PET image fusion may facilitate the targeting of anaplastic foci in homogeneous MRI non-enhancing gliomas for biopsy, may identify oligodendroglial histology preoperatively as well as characterize biologically active tumor volumes within MRI T(1)/FLAIR tumor areas of candidate patients for resection.

EFNS guideline on neuroimaging in acute stroke. Report of an EFNS task force.

Neuroimaging techniques are necessary for the evaluation of stroke, one of the leading causes of death and neurological impairment in developed countries. The multiplicity of techniques available has increased the complexity of decision making for physicians. We performed a comprehensive review of the literature in English for the period 1965-2005 and critically assessed the relevant publications. The members of the panel reviewed and corrected an initial draft, until a consensus was reached on recommendations stratified according to the European Federation of Neurological Societies (EFNS) criteria. Non-contrast computed tomography (CT) scan is the established imaging procedure for the initial evaluation of stroke patients. However, magnetic resonance imaging (MRI) has a higher sensitivity than CT for the demonstration of infarcted or ischemic areas and depicts well acute and chronic intracerebral hemorrhage. Perfusion and diffusion MRI together with MR angiography (MRA) are very helpful for the acute evaluation of patients with ischemic stroke. MRI and MRA are the recommended techniques for screening cerebral aneurysms and for the diagnosis of cerebral venous thrombosis and arterial dissection. For the non-invasive study of extracranial vessels, MRA is less portable and more expensive than ultrasonography but it has higher sensitivity and specificity for carotid stenosis. Transcranial Doppler is very useful for monitoring arterial reperfusion after thrombolysis, for the diagnosis of intracranial stenosis and of right-to-left shunts, and for monitoring vasospasm after subarachnoid hemorrhage. Currently, single photon emission computed tomography and positron emission tomography have a more limited role in the evaluation of the acute stroke patient.

In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram.

BACKGROUND: Escitalopram is a dual serotonin reuptake inhibitor (SSRI) approved for the treatment of depression and anxiety disorders. It is the S-enantiomer of citalopram, and is responsible for the serotonin reuptake activity, and thus for its pharmacological effects. Previous studies pointed out that clinically efficacious doses of other SSRIs produce an occupancy of the serotonin reuptake transporter (SERT) of about 80% or more. The novel radioligand [123I]ADAM and single photon emission computer tomography (SPECT) were used to measure midbrain SERT occupancies for different doses of escitalopram and citalopram. METHODS: Twenty-five healthy subjects received a single dose of escitalopram [5 mg (n=5), 10 mg (n=5), and 20 mg (n=5)] or citalopram [(10 mg (n=5) and 20 mg (n=5)]. Midbrain SERT binding was measured with [(123)I]ADAM and SPECT on two study days, once without study drug and once 6 h after single dose administration of the study drug. The ratio of midbrain-cerebellum/cerebellum was the outcome measure (V3") for specific binding to SERT in midbrain. Subsequently, SERT occupancy levels were calculated using the untreated baseline level for each subject. An Emax model was used to describe the relationship between S-citalopram concentrations and SERT occupancy values. Additionally, four subjects received placebo to determine test-retest variability. RESULTS: Single doses of 5, 10, or 20 mg escitalopram led to a mean SERT occupancy of 60+/-6, 64+/-6, and 75+/-5%, respectively. SERT occupancies for subjects treated with single doses of 10 and 20 mg citalopram were 65+/-10 and 70+/-6%, respectively. A statistically significant difference was found between SERT occupancies after application of 10 and 20 mg escitalopram, but not for 10 and 20 mg citalopram. There was no statistically significant difference between the SERT occupancies of either 10 mg citalopram or 10 mg escitalopram, or between 20 mg citalopram and 20 mg escitalopram. Emax was slightly higher after administration of citalopram (84%) than escitalopram (79%). In the test-retest study, a mean SERT "occupancy" of 4% was found after administration of placebo, the intraclass correlation coefficient was 0.92, and the repeatability coefficient was 0.25. CONCLUSION: SPECT and [123I]ADAM were used to investigate SERT occupancies after single doses of escitalopram or citalopram. The test-retest study revealed good reproducibility of SERT quantification. Similar SERT occupancies were found after administration of equal doses (in respect to mg) of escitalopram and citalopram, giving indirect evidence for a fractional blockade of SERT by the inactive R-citalopram.

Factors influencing quality of life in multiple sclerosis patients: disability, depressive mood, fatigue and sleep quality.

OBJECTIVES: In a series of 504 patients with multiple sclerosis (MS), quality of life (QOL) and its main clinical and demographic determinants were assessed in comparison with healthy individuals. MATERIALS AND METHODS: A postal questionnaire with self-completed measures of disability (Expanded Disability Status Scale, EDSS), QOL (Quality of Life Index, QLI), depressive mood (Self-rating Depression Scale, SDS), fatigue severity (Fatigue Severity Scale, FSS) and sleep quality (Pittsburgh Sleep Quality Index, PSQI) was sent to this sample of MS patients. RESULTS: Most patients were severely disabled; almost half were mildly to severely depressed, suffering from reduced sleep quality and/or fatigue. The multiple sclerosis patients had significantly lower QLI scores than healthy controls. EDSS and SDS scores were found to be predictors of global QLI score. Regarding the different QLI domains, mean SDS scores remained predictive for all QLI items, while mean EDSS, PSQI and FSS scores were only predictive for physical domains. CONCLUSION: Our study clearly demonstrates that depressive mood is the main factor influencing QOL. The disability status, fatigue and reduced sleep quality have an impact mainly on physical domains of life quality.

Familial hemiplegic migraine: follow-up findings of diffusion-weighted magnetic resonance imaging (MRI), perfusion-MRI and [99mTc] HMPAO-SPECT in a patient with prolonged hemiplegic aura.

Familial hemiplegic migraine (FHM) is a rare inherited autosomal dominant disorder. Migraine aura may last up to several weeks and then resolve without sequel. We report a 21-year-old male with FHM since the age of 3 years. Diffusion-weighted magnetic resonance imaging (DWI), perfusion-MR imaging (P-MRI) and [99mTc] hexamethyl-propyleneamine-oxime-single photon emission tomography (HMPAO-SPECT) were performed on day 2, when he was somnolent with right-sided hemiplegia, on day 9 when a mild hemiparesis was still present and on day 24 after recovery. The right central region showed normal findings in DWI, whereas P-MRI and SPECT revealed hyperperfusion on day 2, less marked on day 9, and normal findings on day 24. In conclusion, this case report indicates for the first time, by means of SPECT, P-MRI and DWI studies, that even extremely long-lasting migraine aura is not associated with cerebral ischaemia. Therefore, it supports the revised International Headache Society criteria where the term 'persistent' aura is proposed.

Normal striatal D2 receptor binding in idiopathic restless legs syndrome with periodic leg movements in sleep.

Dopaminergic treatment is very effective in restless legs syndrome (RLS) and periodic leg movements in sleep (PLMS). However, neuroreceptor imaging studies that addressed altered striatal dopaminergic function have given controversial results. In this present study, 14 patients with idiopathic RLS (iRLS) and PLMS with a good response to dopaminergic and non-dopaminergic treatment and ten healthy sex- and age-matched controls were investigated off-medication by using 123I-IBZM and SPECT. RLS symptoms and sleep disturbances were evaluated using three nights of polysomnography, the Pittsburgh Sleep Quality Index, and the International RLS Study Group (IRLSSG) rating scale. The patients presented with sleep disturbances, a high PLMS index (56.2 +/- 33.1 per h), and severe RLS symptoms during SPECT (IRLSSG rating scale 23.1 +/- 8.0), and showed no significant differences in striatal to frontal IBZM binding to D2 receptors compared to controls (ratio striatum/frontal cortex, right side 1.60 +/- 0.10 vs 1.63 +/- 0.08, P = 0.35, NS; left side 1.61 +/- 0.11 vs 1.63 +/- 0.08, P = 0.51, NS). These findings show normal function of striatal D2 receptors in successfully treated patients with iRLS and PLMS. Dopaminergic and non-dopaminergic pretreatment does not appear to change striatal D2 receptor binding as compared to healthy controls. Structures other than striatal D2 receptors are discussed as possible causes of the treatment effects in RLS.

[PET and SPECT investigations in Alzheimer's disease]. / Nuklearmedizin und Demenz--Anwendung bei Morbus Alzheimer.

Nuclear medicine offers a wide range of possibilities to investigate dementia. Various SPECT and PET tracers will be introduced in this article first. Different questions concerning evaluation of dementia are discussed taking Alzheimer's disease (AD) as an example. It is important to perform nuclear medicine investigations on high technical level, using standardized methods as statistical parametric mapping (SPM) for evaluation. If neuroprotective therapies are available, an early diagnosis, the determination of risk factors and longitudinal investigations will be the focus of interest and the main goal of nuclear medicine. Apart from measuring cerebral perfusion and glucose metabolism the development of new ligands, concerning the cholinergic system and the visualization of amyloid plaques, is of great importance.

Sequential MRI in a case of Creutzfeldt-Jakob disease.

A 48-year-old man suddenly developed clinically and electroencephalographically nonspecific dementia. On MRI sequences, only diffusion-weighted images (DWI) of the cortex were unequivocally pathological. Obvious atrophy and basal ganglia signal changes appeared only 9 months after the onset. Brain biopsy confirmed Creutzfeldt-Jakob disease (CJD). In rapidly progressive dementia, we recommend DWI for early diagnosis of CJD.

Dopamine transporter availability in symptomatic depressed patients with seasonal affective disorder and healthy controls.

BACKGROUND: During recent years hypotheses about the pathophysiology of seasonal affective disorder/winter type (SAD) have focused monoaminergic mechanisms. There is substantial evidence that serotonergic systems play an important role. The potential role of catecholaminergic pathways has not been fully explored. METHODS: Eleven drug-free, symptomatic depressed patients with SAD and 11 healthy age- and gender-matched healthy controls were invited to participate in a 123Ibeta-CIT single photon emission computed tomography (SPECT) study to assess striatal density of dopamine transporters (DATs). The cerebellum was used as reference region. Ratios were calculated between mean counts in left and right striatum and cerebellum. These ratios minus I represent specific/non-displaceable binding and are assumed to be directly related to DAT availability at the time of binding equilibrium. RESULTS: Displaceable 153Ibeta-CIT binding in the area corresponding to the left striatum was significantly reduced in SAD patients compared to healthy controls (10.49+/-0.91 v. 1195+/-1.54, respectively; 2-tailed P = 0.017, Mann-Whitney U test). CONCLUSIONS: These data suggest reductions in the availability of striatal DAT binding sites in untreated symptomatic depressed SAD patients. It remains unclear whether these reductions represent a primary defect or an attempt to overcome a state of possible lowered dopamine availability in the synaptic cleft during a depressive episode of SAD. However, these findings provide evidence that brain dopaminergic systems may be involved in the pathophysiology of SAD.

In vivo (123)I IBZM SPECT imaging of striatal dopamine 2 receptor occupancy in schizophrenic patients.

RATIONALE: Single photon emission computed tomography (SPECT) using (123)I iodobenzamide (IBZM) as tracer substance has been shown to be a useful tool to visualize dopamine 2 (D2) receptor occupancy. OBJECTIVES: We investigated the striatal D2 receptor occupancy of zotepine which is referred to the class of atypical antipsychotic drugs. METHODS: (123)I IBZM and SPECT were used to visualize striatal dopamine 2 (D2) receptor occupancy in zotepine-treated schizophrenic patients. Two groups of schizophrenic patients receiving either 150 mg/day zotepine (n=6) or 300 mg/day (n=6) underwent examination. For the quantification of striatal D2 receptor occupancy, striatal IBZM binding in patients treated with antipsychotics was compared to untreated healthy controls (n=8) reported earlier. RESULTS: Zotepine led to a mean overall striatal D2 receptor occupancy of 73%. Patients with 150 mg daily showed a significantly lower occupancy (65.8%, SD=6.2) than patients with 300 mg/day (77.8%, SD=10.7; P<0.05). No clinically relevant extrapyramidal side effects occurred during treatment with zotepine. CONCLUSIONS: There was no correlation between the degree of striatal D2 receptor occupancy and clinical improvement.

Nuclear medicine in the preoperative evaluation of epilepsy.

The clinical usefulness of nuclear medicine in the preoperative evaluation of epilepsy is highlighted with regard to non-lesional temporal lobe epilepsy, extratemporal epilepsy, bitemporal interictal epileptiform discharges (IEDs) and in dual pathology and cortical dysgenesis. Ictal single photon emission computed tomography (SPECT) shows good sensitivities in the correct lateralization of an electroencephalogram-defined epileptic focus in lesional and, to a lesser extent, non-lesional epilepsy. Positron emission tomography (PET) using 18F-fluorodeoxyglucose or 11C-flumazenil gives a good detection rate of the seizure onset zone in non-lesional cases and extratemporal epilepsy. The investigation of patients with bitemporal IEDs can confirm the existence of bitemporal seizure onset. For patients with a dual pathology or cortical dysgenesis nuclear medicine offers the opportunity to delineate the existence or extension of abnormalities possibly responsible for the seizure disorder.

No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism.

BACKGROUND: A polymorphism in the serotonin transporter promoter gene region (5-HTTLPR) has been shown to influence the quantity of serotonin transporter expressed in human cell lines: the 5-HTTLPR short allele (s) has been associated with reduced 5-HTT expression when compared to cells carrying the 5-HTTLPR long allele (l). We performed a single photon emission computed tomography (SPECT) study using the ligand [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT) to measure 5-HTT availability in 16 healthy subjects genotyped for 5-HTTLPR. METHODS: SPECT scans were performed 24 hours after tracer injection, regions of interest anatomically corresponding to the thalamus-hypothalamus and mesencephalon-pons areas were compared to the binding in the cerebellum, representing the nondisplaceable [(123)I]-beta-CIT-binding (results expressed as target activity minus cerebellum activity/cerebellum activity). DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods. RESULTS: Specific binding ratios in the thalamus-hypothalamus were 2.65 +/- 0.4 in subjects with the l/l genotype (n = 3), 2.76 +/- 0.5 in subjects with the l/s genotype (n = 9), and 2.77 +/- 0.4 in subjects with the s/s genotype (n = 4). Binding ratios in the mesencephalon-pons were 1.43 +/- 0.3 (l/l; n = 3), 1.37 +/- 0.3 (l/s; n = 9), and 1.28 +/- 0.3 (s/s; n = 4). None of these differences was statistically significant. CONCLUSIONS: Our data provide no evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects.

A medial to lateral shift in pre-movement cortical activity in hemi-Parkinson's disease.

OBJECTIVE: Recent evidence suggests that cortical activity associated with voluntary movement is relatively shifted from medial to lateral premotor areas in Parkinson's disease. This shift occurs bilaterally even for unilateral responses. It is not clear whether the shift in processing reflects an overall change in movement strategy, thereby involving alternate cortical areas, or reflects a compensatory change whereby, given the appropriate conditions, less impaired cortical areas are able to provide a similar function in compensation for those areas which are more impaired. This issue was examined in patients with hemi-Parkinson's disease, in whom basal ganglia impairment is most pronounced in one hemisphere. METHODS: Fourteen patients with hemi-Parkinson's disease and 15 age-matched control subjects performed a Go/NoGo finger movement task and the contingent negative variation (CNV) was recorded from 21 scalp positions. RESULTS AND CONCLUSIONS: Maximal CNV amplitudes were found over central medial regions for control subjects, but were shifted more frontally for Parkinson's disease patients, reduced in amplitude over the midline and lateralized towards the side ipsilateral to the greatest basal ganglia impairment. This shift in cortical activity from medial to lateral areas in Parkinson's disease patients appears to reflect a compensatory mechanism operating predominantly on the side of greatest basal ganglia impairment.

[123I] beta-CIT and single photon emission computed tomography reveal reduced brain serotonin transporter availability in bulimia nervosa.

BACKGROUND: Impaired serotonin transmission has been implicated in the pathophysiology of eating disorders. We investigated the in vivo availability of brain serotonin transporters and dopamine transporters in bulimia nervosa patients. METHODS: Approximately 24 hours after injection of [123I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I] beta-CIT), single photon emission computed tomography scans were performed in 10 medication-free, female bulimic patients and 10 age-matched, healthy females. For quantification of brain serotonin transporter and dopamine transporter availability, a ratio of specific to nonspecific [123I] beta-CIT brain binding was used (V(3)" = target region - cerebellum/cerebellum). RESULTS: Drug-free bulimia nervosa patients showed a 17% reduced brain serotonin transporter availability in the hypothalamus and thalamus, as compared with healthy control subjects (2.4 +/- 0.4 vs. 2.9 +/- 0.4, p =.026), and a similar reduction in striatal dopamine transporter availability. There was a negative correlation of illness duration and serotonin transporter availability (r = -.65; p =.042) and a strong positive correlation between hypothalamic/thalamic and striatal V(3)" (r =.80, p <.001). CONCLUSIONS: This first report of reduced [123I] beta-CIT binding in a relatively small group of patients with bulimia nervosa suggests a reduced hypothalamic and thalamic serotonin transporter availability in bulimia, which is more pronounced with longer duration of illness.