Textural features of hypoxia PET predict survival in head and neck cancer during chemoradiotherapy.

PURPOSE: The aim of this study was to investigate whether textural features of tumour hypoxia, assessed with serial [18F]fluoromisonidazole (FMISO)-PET, were able to predict clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC, T1-4, N+, M0) during chemoradiotherapy (CRT). METHODS: In a preliminary evaluation of a prospective trial, tumour hypoxia was evaluated in 29 patients via serial FMISO-PET before and during CRT. All patients received an initial [18F]fluorodeoxyglucose (FDG)-PET before CRT, and tumour regions were defined on this FDG-PET. The first-order metrics tumour-to-background ratio (TBRmean, TBRmax, TBRpeak), coefficient of variation, total lesion uptake and integral non-uniformity were calculated for all scans. Further, 3 second-order (textural) features from two grey-level matrices were calculated, as well as differential non-uniformity (udiff). Prognostic value was examined by median split for group separation (GS) in Kaplan-Meier estimates and correlated with overall survival (OS), quantified via log-rank tests (p ≤ 0.05) and group-relative hazard ratios (HR). RESULTS: Within a median follow-up of 29.6 months (95% CI: 16.8-48.0 months), no first-order metrics predicted OS with a significant GS (all p > 0.05) on any FMISO-PET scan. Only udiff before and in week 2 during CRT (p = 0.03, HR = 10.8 and p = 0.05, HR = 5.2) and non-uniformity from grey-level run length matrix in week 2 separated prognostic groups (p = 0.05, HR = 5.3); lower values were correlated with better OS. Further, the decrease in udiff from before CRT to week 2 was correlated with better OS (p = 0.04, HR = 9.4). FDG-PET before CRT did not predict outcome in any measure. CONCLUSIONS: Textural features on FMISO-PET scans before CRT, in week 2 and, to a limited degree, the change of features during CRT, were able to identify head and neck squamous cell carcinoma patients with better OS, suggesting that a higher homogeneity of the degree of hypoxia in tumours could correlate with a better outcome after CRT.

Comparison of PET/CT and whole-mount histopathology sections of the human prostate: a new strategy for voxel-wise evaluation.

BACKGROUND: Implementation of PET/CT in diagnosis of primary prostate cancer (PCa) requires a profound knowledge about the tracer, preferably from a quantitative evaluation. Direct visual comparison of PET/CT slices to whole prostate sections is hampered by considerable uncertainties from imperfect coregistration and fundamentally different image modalities. In the current study, we present a novel method for advanced voxel-wise comparison of histopathology from excised prostates to pre-surgical PET. Resected prostates from eight patients who underwent PSMA-PET/CT were scanned (ex vivo CT) and thoroughly pathologically prepared. In vivo and ex vivo CT including histopathology were coregistered with three different methods (manual, semi-/automatic). Spatial overlap after CT-based registration was evaluated with dice similarity (DSC). Furthermore, we constructed 3D cancer distribution models from histopathologic information in various slices. Subsequent smoothing reflected the intrinsically limited spatial resolution of PSMA-PET. The resulting histoPET models were used for quantitative analysis of spatial histopathology-PET pattern agreement focusing on p values and coefficients of determination (R 2). We examined additional rigid mutual information (MI) coregistration directly based on PSMA-PET and histoPET. RESULTS: Mean DSC for the three different methods (ManReg, ScalFactReg, and DefReg) were 0.79 ± 0.06, 0.82 ± 0.04, and 0.90 ± 0.02, respectively, while quantification of PET-histopathology pattern agreement after CT-based registration revealed R 2 45.7, 43.2, and 41.3% on average with p < 10-5. Subsequent PET-based MI coregistration yielded R 2 61.3, 55.9, and 55.6%, respectively, while implying anatomically plausible transformations. CONCLUSIONS: Creating 3D histoPET models based on thorough histopathological preparation allowed sophisticated quantitative analyses showing highly significant correlations between histopathology and (PSMA-)PET. We recommend manual CT-based coregistration followed by a PET-based MI algorithm to overcome limitations of purely CT-based coregistrations for meaningful voxel-wise comparisons between PET and histopathology.

Long-term characterization of the Flinders Sensitive Line rodent model of human depression: Behavioral and PET evidence of a dysfunctional entorhinal cortex.

The etiology of depression is unknown but has been associated with dysregulation of neuronal activity at numerous loci on the limbic-cortical circuitry. The Flinders Sensitive Line (FSL) is a validated rodent model of human depression with spontaneously emerging behavioral and physiological phenotype, however, the durability and robustness of the phenotypes have not been described. The objective of the current study was to evaluate longitudinal dynamics of the depressive-like symptoms in this animal model. FSL and control rats of both genders were assessed over 8 months, characterizing their performance at different time points on motor, sensorimotor and complex learning/memory based tasks. Changes over time in physiological parameters, such as corticosterone and blood glucose levels, were monitored. Regional glucose metabolism, used as a marker of neuronal activity, was assessed at different time points using F18-FDG Positron Emission Tomography (PET). Results show that certain deficits at 2-3 months--on tests such as the Elevated Plus Maze, Object Recognition, and the Forced Swim Test--were transitory and the phenotype was no longer present when re-testing at 6-7 months of age. However, a stable impairment was detected on a learning and memory task, particularly indicating dysfunction in retention of spatial information. Furthermore, at multiple time points, the PET scan indicated a significate bilateral, hypo-metabolism in the temporal lobes in the FSL rats compared to healthy controls. The data suggests possible alterations of entorhinal cortex metabolism concomitant with specific behavioral changes and supports the importance of understanding the dynamics and the time and gender dependence of the phenotypes present.

[Differential diagnostics of Parkinson's disease with nuclear medicine procedures]. / Differenzialdiagnostik des Parkinson-Syndroms mit nuklearmedizinischen Verfahren.

Early differential diagnosis of parkinsonism is of paramount therapeutic and prognostic importance. In the present review, the diagnostic value of routinely used nuclear medicine procedures is presented and critically discussed. The [(123)I]FP-CIT single-photon emission computed tomography (SPECT) is the method of choice for differentiation between neurodegenerative and non-neurodegenerative parkinsonism. The [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) method provides a very high diagnostic accuracy for differentiating between Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), which is clearly superior to the accuracy of [(123)I]FP-CIT SPECT, [(123)I]IBZM SPECT and [(123)I]MIBG scintigraphy. Furthermore, [(18)F]FDG-PET is the only of the aforementioned techniques that also allows a reliable differentiation between APS subgroups (e.g., multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration). Current studies are investigating the probable value of [(18)F]FDG-PET for risk stratification of dementia in PD.

Transcranial sonography and [18F]fluorodeoxyglucose positron emission tomography for the differential diagnosis of parkinsonism: a head-to-head comparison.

BACKGROUND AND PURPOSE: Brain imaging with positron emission tomography using [(18) F]fluorodeoxyglucose (FDG-PET) and transcranial B-mode sonography (TCS) improves the differential diagnosis of parkinsonism. The diagnostic merits of these approaches in identifying and differentiating atypical parkinsonian syndromes (APS) are compared. METHODS: Data were included from 36 patients with clinically suspected APS who underwent PET and TCS. FDG-PET scans were analyzed by visual assessment (including voxel-based statistical maps) of a priori defined disease-specific metabolic patterns. Sonographers achieved diagnoses according to pre-defined criteria for echogenicities of the substantia nigra and lenticular nucleus, and third ventricle diameter. Patients with APS were identified and allocated to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). RESULTS: After a median follow-up period of 9 months, the final clinical diagnoses (reference standard) were Parkinson's disease, n = 15; MSA, n = 9; PSP, n = 7; and CBD, n = 5 (n = 21 APS in total). Six patients (4 APS) showed an insufficient bone window for TCS. In the remaining 30 patients, sensitivity/specificity for diagnosing APS were 82%/100% and 82%/85% for FDG-PET and TCS, respectively. Diagnostic accuracies did not differ between FDG-PET (90%) and TCS (83%; P = 0.69). Likewise, overall accuracy of subgroup classification (non-APS, MSA, PSP and CBD) did not differ between modalities (FDG-PET 87% and TCS 83%; P = 1.00). CONCLUSIONS: FDG-PET and TCS show comparable accuracies for differential diagnosis of neurodegenerative parkinsonism. This preliminary study supports the use of TCS and warrants further prospective validation.

Ectopic ACTH-syndrome due to a neuroendocrine tumour of the appendix.

Ectopic ACTH production causes 10% of Cushing's syndromes. The diagnostic workup is difficult, can last more than 6 months (> 50% of cases), and the underlying tumour is still frequently not located (12%). Carcinoid tumours of the appendix are frequent and are revealed in 0.3% of patients undergoing routine appendectomy. However, neuroendocrine tumours of the appendix with ACTH production are an extremely rare entity. Here we report the case of a female patient with clinically overt Cushing's syndrome due to ectopic ACTH-production from a carcinoid tumour of the appendix. During the diagnostic workup, repeated endocrine tests, multiple different imaging modalities and frequent and lengthy hospitalisations were necessary. Wrongly, even a neurosurgical pituitary exploration was performed. After 12 months from the initial admission, the tumour was finally detected by an ¹8F-fluoro-L-dihydroxyphenylalanine (¹8FDOPA PET) and an appendectomy followed by right hemicolectomy were performed. The patient recovered rapidly and the symptoms from the hypercortisolism were no more present.In this case, we discuss the multitude of problems, which may delay the diagnosis and the pitfalls, that should be avoided in order to locate the tumour and to initiate adequate therapy as early as possible. Furthermore, our case demonstrates the complexity of diagnostic procedures, which demand most of the times a multidisciplinary approach. In this setting, regular follow-ups in short time intervals and the use of novel imaging techniques can finally cut the diagnostic "Gordian knot".

Improved visual [(123)I]FP-CIT SPECT interpretation for evaluation of parkinsonism by visual rating of parametric distribution volume ratio images.

AIM: Imaging of presynaptic dopamine transporters (DAT) by single-photon emission computed tomography (SPECT) and [(123)I]FP-CIT is an established method for differentiating between neurodegenerative and non-neurodegenerative parkinsonism. Whereas a region-of-interest (ROI) analysis is the method of choice for analyzing [(123)I]FP-CIT SPECT studies, visual image interpretations can also provide highly accurate results. The present study was undertaken to validate a visual reading system for parametric volume of distribution (DVR) [(123)I]FP-CIT SPECT images that combines the quantitative nature of ROI analyses and the simplicity of visual readings. METHODS: A 9-step linear visual rating template for semi-quantitative DVR ratings of caudate nucleus and putamen was developed (VRDVR). The conventional 4-step visual reading system that is mainly based on the [(123)I]FP-CIT uptake pattern was used for comparison (VRP method). Six independent observers retrospectively rated the [(123)I]FP-CIT scans of 30 consecutive parkinsonism and tremor patients (N.=16 neurodegenerative, N.=14 non-neurodegenerative) using VRDVR and VRP. In addition, a highly trained investigator performed manual ROI analyses. RESULTS: The ROI analysis provided complete separation of both patient groups by comparing the lower DAT binding of both putamina (i.e., putamen contralateral to clinically most affected side in neurodegenerative parkinsonism). Using VRP, the two most experienced observers correctly classified all patients while 20 false-positive ratings occurred in the less experienced observers (mean area under the receiver operating characteristic curve [AUCROC] of all observers 0.93±0.07). The VRDVR ratings of the two most experienced observers did not overlap between patient groups, although at different VRDVR score cut-offs. Using the same VRDVR score cut-off for all observers, only six false-negative and one false-positive ratings occurred in total (AUCROC 0.99±0.01). Inter-observer agreement was good for VRP and VRDVR. Moreover, semi-quantitative VRDVR and quantitative ROI analyses showed a strong correlation in all observers (Spearman's rho, 0.85-0.91). CONCLUSIONS: The proposed VRDVR method offers a very promising visual analysis method for [(123)I]FP-CIT SPECT studies in parkinsonism. The accuracy of VRDVR readings was found to be superior to conventional VRP, while it provided a diagnostic accuracy in less experienced observers that is comparable to manual ROI analyses by a highly trained investigator.

Evaluation of FDG-PET for detecting lymph node metastasis in uterine corpus cancer.

BACKGROUND: In order to decrease surgery-related morbidity, we evaluated the reliability of the evaluation of lymph node metastasis in patients with uterine corpus cancer by positron-emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) before surgical staging. MATERIALS AND METHODS: Patients with newly diagnosed uterine corpus cancer scheduled for surgical staging, including lymphadenectomy, underwent PET imaging within 30 days before surgery. PET results and postoperative histopathology were compared for each patient and each nodal site. Sensitivity, specificity, positive and negative predictive value (PPV/NPV) as well as accuracy of FDG-PET in predicting nodal disease was determined by joined meta-analysis of the present data and the data available in the literature. RESULTS: Of 21 patients examined, 13 patients were eligible to enter this pilot study. Only one patient had lymph node metastasis, which was preoperatively detected by FDG-PET scan. Additionally, another patient was considered to have lymph node metastasis according to increased focal FDG uptake; however, all lymph nodes were free of malignant disease upon final pathology. In contrast, all other patients without lymph node metastasis upon final pathology showed negative preoperative FDG-PET scans. The meta-analysis yielded a sensitivity, specificity, PPV, NPV and accuracy of 0.53, 0.91, 0.57, 0.90 and 0.84, respectively. CONCLUSION: In patients with uterine corpus cancer, FDG-PET had an insufficient positive predictive value in detecting lymph node metastases, indicating that this method cannot replace surgical staging. However, due to its high NPV, FDG-PET might be beneficial in selected patients who are poor candidates for surgical staging.

[Neuroimaging in medicine]. / Wissenschaftliche Neurobildgebung in der Medizin.

Neuroimaging has in recent years greatly contributed to our understanding of a wide range of aspects of central neurological diseases. These include the classification and localization of disease (e.g., in headache), the understanding of pathology (e.g., in Parkinson's disease), mechanisms of reorganization (e.g., in stroke), and the subclinical progress of disease (e.g., in degenerative diseases). Apart form presurgical mapping, clinical applications of fMRI are limited. However, functional imaging enables the formulation of neurobiological hypotheses that can be tested clinically and is suited to test classical clinical hypotheses about how the brain works. Understanding the mechanisms and the site of pathology, e.g., in cluster headaches, will lead and has led to new therapeutic strategies. New methodological developments for neuroscientific applications are aimed at the integration of functional and morphological connectivity through a combination of magnetic resonance techniques (fMRI, DTI) and electrophysiological (EEG, MEG) recordings. In addition to stimulus-dependent activations, resting state activity has found increasing interest, for example, in sleep research and various psychiatric diseases (e.g., schizophrenia, borderline).

IBZM SPECT and FDG PET in the differential diagnosis of Parkinsonian syndromes: comparison with respect to inter-rater agreement.

AIM: Both IBZM SPECT and FDG PET may be used for differentiation between Parkinson's disease (PD) and atypical neurodegenerative parkinsonian syndromes (APS). However, there are only very limited data of both modalities in the same subjects. The present study compared both modalities with respect to inter-rater agreement in 30 patients with neurodegenerative parkinsonian syndromes (PS) confirmed by FP-CIT SPECT. METHODS: IBZM SPECT and FDG PET were categorized as PD or APS by visual inspection of standardized report pages and statistical parametric maps (SPMs). Categorization was performed independently by five readers. Inter-rater agreement was quantified using Cohen's kappa kappa. RESULTS: IBZM SPECT resulted in PD and APS in 11 and 19 cases, respectively (majoritarian categorization). Inter-rater agreement was kappa=0.64+/-0.10. FDG PET resulted in PD and APS in 12 and 18 cases, respectively (majoritarian categorization). Inter-rater agreement was kappa=0.68+/-0.07. Majoritarian diagnosis disagreed between IBZM SPECT and FDG PET in 13 cases (43%). Semi-quantitative analysis of IBZM SPECT using the striatum-to-reference distribution volume ratio was in good agreement with visual categorization (area under ROC curve 0.92). CONCLUSION: In neurodegenerative PS, inter-rater agreement of visual analysis is substantial in both IBZM SPECT and FDG PET. Furthermore, (I) visual analysis of IBZM SPECT is reliable if adequate standardized image display is used, (II) visual analysis of FDG SPMs allows unique categorization as either PD or APS in most subjects, and (III) IBZM SPECT and FDG PET are discordant in a significant fraction of cases.

[Stunning in radioiodine therapy of benign thyroid disease. Quantification and therapeutic relevance]. / Stunning in der Radioiodtherapie benigner Schilddrüsenerkrankungen: Effektquantifizierung und therapeutische Relevanz.

UNLABELLED: In radioiodine therapy of benign thyroid disease, a reduction of radioiodine uptake is known for consecutive administrations of 131I, which needs to be considered in therapy planning. AIM: Analysis of uptake reduction with regard on the time interval between radioiodine administration and the delivered dose to the thyroid tissue. PATIENTS, METHODS: 200 patients were enrolled in the study and distributed into two groups (matched for diagnoses), each containing 32 patients with Graves' disease (target dose 250 Gy), 24 with focal (400 Gy), 44 with disseminated thyroid autonomy (150 Gy). In one group, a second fraction of radioiodine was given after 48 h (2d) due to an unexpected low radioiodine uptake or effective half-life, whereas in the other group the second fraction was given after 96 h (4d). RESULTS: There was no significant difference between delivered doses due to the first fraction after four days: 2d: 86+/-48 Gy (extrapolated) vs. 4d: 87+/-41 Gy, p>0.05. In 2d, delivered dose at time of second administration was significantly lower (51+/-29 Gy) than in 4d (p<0.01). The radioiodine uptake of the second fraction relative to the initial uptake was significantly lower in the 4d (4d: 63+/-25% vs. 2d: 82+/-24%, p<0.01). In addition, a correlation between uptake reduction and delivered dose and an influence of the time interval between radioiodine administrations could be shown. CONCLUSIONS: Relative uptake of subsequent radioiodine fractions decreases with time after first administration and with increasing delivered dose to the thyroid. If a second fraction of 131I is given at an earlier time, the same therapeutic effect can be reached using lower amounts of activity, minimising radiation exposure and increasing efficiency of radioiodine therapy.

Positron emission tomography study of regional cerebral blood flow and flow-metabolism coupling during general anaesthesia with xenon in humans.

BACKGROUND: The effects of xenon on regional cerebral blood flow (rCBF) are controversial. Moreover, the precise sites of action at which xenon exerts its effects in the human brain remain to be established. METHODS: rCBF was sequentially assessed by H(2)(15)O positron emission tomography in six volunteers. rCBF was determined at baseline and during general anaesthesia induced with propofol and maintained with one minimum alveolar concentration xenon. rCBF measurements were started after the calculated plasma concentration of propofol had decreased to subanaesthetic levels (<1.0 microg ml(-1)). Changes in rCBF were calculated for 13 cerebral volumes of interest by measurement of a semi-quantitative perfusion index (PI). In addition, voxel-wise changes in rCBF were analysed using statistical parametric mapping. RESULTS: Xenon had only minor effects on PI in grey matter volumes of interest. In contrast, PI was increased in white matter [from 1.01 (0.11) to 1.24 (0.15) kcnt ml(-1) MBq(-1), P=0.05, mean (SD)]. Voxel-based analysis showed an increase of rCBF in white matter and a relative decrease of rCBF during xenon anaesthesia in distinct grey matter regions, particularly the orbito- and mesiofrontal cortex, cingulate gyrus, thalamus, hippocampus and bilateral cerebellum (P<0.05 corrected). When correlating PI with cerebral metabolic rate of glucose (previously obtained in another group of six volunteers using (18)F-fluorodeoxyglucose as tracer), the flow-metabolism coupling was preserved during xenon anaesthesia. CONCLUSIONS: Xenon exerted distinct regional effects on CBF: relative decreases in several cortical, subcortical, and cerebellar areas were accompanied by an increase in white matter. Flow-metabolism coupling was not impaired during xenon anaesthesia.

Preoperative motor system brain mapping using positron emission tomography and statistical parametric mapping: hints on cortical reorganisation.

OBJECTIVES: This study investigated the applicability of statistical parametric mapping (SPM) for analysing individual preoperative brain mapping studies in patients with cerebral mass lesions for neurosurgical planning. The study further investigated if hints on functional reorganisation processes can be found. METHODS: Nine adult patients with cerebral mass lesions underwent activation [(15)O]water-PET under stimulation by finger (n=9) and foot (n=4) movement. Individual SPM-t-maps were computed without anatomical normalisation and coregistered to the individual magnetic resonance imaging. Relative cerebral blood flow change maps were calculated for comparison. RESULTS: The spatial relation between the sensorimotor cortex and the lesion could be determined in all cases. Additional activations covered the ipsilateral sensorimotor cortex and the bilateral cerebellum, premotor cortices and supplementary motor areas. Patients with motor symptoms of the stimulated hand (paresis, focal seizures) activated the ipsilateral premotor cortices and contralateral cerebellum more often than patients without motor symptoms. The SPM results for p<0.005 and cerebral blood flow change maps showed considerably overlapping motor area activations. For p<0.001, SPM missed three sensorimotor cortex activations depicted by cerebral blood flow change maps and by SPM for p<0.005 in typical localisation. SPM analyses showed less activations probably unrelated to task performance. CONCLUSION: It is concluded that SPM provides an efficient method for analysing individual preoperative PET activation studies. Activations of the ipsilateral premotor cortices and contralateral cerebellum may indicate an enhanced recruitment of ipsilateral motor pathways evoked by functional reorganisation processes. However, this changed activation pattern was not necessarily associated with a better neurological status.

Functional MRI and 18F FDG-positron emission tomography for presurgical planning: comparison with electrical cortical stimulation.

BACKGROUND: In patients with mass lesions near "eloquent" cortical areas different preoperative mapping techniques can be used. Two of the most widely used approaches include positron emission tomography (PET) and functional MRI (fMRI). We employed both methods in the same patients undergoing presurgical evaluation and compared the results to those obtained by direct electrical cortical stimulation (DECS). METHOD: 22 patients with tumours of different aetiology near the central region were investigated. FMRI was performed using a T2(*)-weighted gradient-echo BOLD sequence at 1.5 T, PET was performed after injection of 122-301 MBq (18)F-Fluorodeoxyglucose (18-FDG) under rest and activation conditions. DECS was performed in all patients with recordings of muscles primarily involved in the investigated tasks. FINDINGS: In 19 patients all three modalities could be compared, 1 patient demonstrated discordance between fMRI and PET with DECS speaking in favour of fMRI, 6 patients had neighbouring results of PET and fMRI (between 1-2 cm distance), 12 patients had overlapping results. INTERPRETATION: The high incidence of neighbouring results is presumably related to fMRI specific artefacts. Advantages of fMRI are: Higher spatial and temporal resolution, more and different functional runs, shorter examination time, wider availability, longitudinal examinations, non-invasiveness and cost-effectiveness, easy registration to anatomical images. Advantages of PET are: higher signal-to-noise ratio, lesser susceptibility to artefacts (motion, draining veins), evaluation of tumour metabolism. It is our opinion that the neurosurgeon has to decide on a case-by-case basis which study suits his specific needs in the presurgical evaluation of his patient.

Metabolic and electrophysiological validation of functional MRI.

OBJECTIVES: Although functional MRI is widely used for preoperative planning and intraoperative neuronavigation, its accuracy to depict the site of neuronal activity is not exactly known. Experience with methods that may validate fMRI data and the results obtained when coregistering fMRI with different preoperative and intraoperative mapping modalities including metabolically based (18)F-fluorodeoxyglucose PET, electrophysiologcally based transcranial magnetic stimulation (TMS), and direct electrical cortical stimulation (DECS) are described. METHODS: Fifty patients were included. PET was performed in 30, TMS in 10, and DECS in 41 patients. After coregistration using a frameless stereotactic system, results were grouped into overlapping (<1 cm distance), neighbouring (<2 cm), or contradictory (>2 cm). RESULTS: Comparing fMRI with PET, 18 overlapping, seven neighbouring, and one contradictory result were obtained. In four patients no comparison was possible (because of motion artefacts, low signal to noise ratio, and unusual high tumour metabolism in PET). The comparison of TMS and fMRI showed seven overlapping and three neighbouring results. In three patients no DECS results could be obtained. Of the remaining 38 patients, fMRI hand motor tasks were compared with DECS results of the upper limb muscles in 36 patients, and fMRI foot motor tasks were compared with DECS results of the lower limb on 13 occasions. Of those 49 studies, overlapping results were obtained in 31 patients, and neighbouring in 14. On four occasions fMRI did not show functional information (because of motion artefacts and low signal to noise). CONCLUSIONS: All validation techniques have intrinsic limitations that restrict their spatial resolution. However, of 50 investigated patients, there was only one in whom results contradictory to fMRI were obtained. Although it is not thought that fMRI can replace the intraoperatively updated functional information (DECS), it is concluded that fMRI is an important adjunct in the preoperative assessment of patients with tumours in the vicinity of the central region.

Localisation of motor areas in brain tumour patients: a comparison of preoperative [18F]FDG-PET and intraoperative cortical electrostimulation.

Assessment of the exact spatial relation between tumour and adjacent functionally relevant brain areas is a primary tool in the presurgical planning in brain tumour patients. The purpose of this study was to compare a preoperative fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) activation protocol in patients with tumours near the central area with the results of intraoperative direct cortical electrostimulation, and to determine whether non-invasive preoperative PET imaging can provide results equivalent to those achieved with the invasive neurosurgical "gold standard". In this prospective study, we examined 20 patients with various tumours of the central area, performing two PET scans (each 30 min after i.v. injection of 134-341 MBq [18F]FDG) in each patient: (1) a resting baseline scan and (2) an activation scan using a standardised motor task (finger tapping, foot stretching). Following PET/MRI realignment and normalisation to the whole brain counts, parametric images of the activation versus the rest study were calculated and pixels above categorical threshold values were projected to the individual MRI for bimodal assessment of morphology and function (PET/MRI overlay). Intraoperative direct cortical electrostimulation was performed using a Viking IV probe (5 pulses, each of 100 micros) and documented using a dedicated neuro navigation system. Results were compared with the preoperative PET findings. PET revealed significant activation of the contralateral primary motor cortex in 95% (19/20) of the brain tumour patients (hand activation 13/13, foot activation 6/7), showing a mean increase in normalised [18F]FDG uptake of 20.5% +/- 5.2% (hand activation task) and 17.2% +/- 2.5% (foot activation task). Additionally detected activation of the ipsilateral primary motor cortex was interpreted as a metabolic indication for interhemispheric compensational processes. Evaluation of the PET findings by cortical stimulation yielded a 94% sensitivity and a 95% specificity for identification of motor-associated brain areas. In conclusion, the findings indicate that a relatively simple and clinically available [18F]FDG PET activation protocol enables a sufficiently precise assessment of the local relation between the intracranial tumour and the adjacent motor cortex areas and may facilitate the presurgical planning of tumour resection.

Inter-modality comparisons of seizure focus lateralization in complex partial seizures.

Anterior temporal lobectomy offers a high chance of seizure-free outcome in patients suffering from drug-refractory complex partial seizure (CPS) originating from the temporal lobe. Other than EEG, several functional and morphologic imaging methods are used to define the spatial seizure origin. The present study was undertaken to compare the merits of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), magnetic resonance imaging (MRI) and single-voxel proton MR spectroscopy (MRS) for the lateralization of temporal lobe seizure foci. The clinical charts and imaging data of 43 consecutive CPS patients were reviewed. Based on surface EEG, 31 patients were classified with temporal lobe epilepsy (TLE; 25 lateralized, 6 not lateralized) and 12 with non-temporal lobe epilepsy. All were examined by FDG-PET, MRS and MRI within 6 weeks. FDG-PET and MRI were interpreted visually, while the N-acetyl-aspartate to creatine ratio was used for MRS interpretation. One FDG-PET scan was invalid due to seizure activity post injection. The MR spectra could not be evaluated in five cases bilaterally and three cases unilaterally for technical reasons. A total of 15 patients underwent anterior temporal lobectomy. All showed a beneficial postoperative outcome. When the proportions of agreement between FDG-PET (0.77), MRI (0.58) and MRS (0.56) and surface EEG in TLE cases were compared, there were no significant differences (P>0.10). However, FDG-PET showed a significantly higher agreement (0.93) than MRI (0.60; P=0.03) with the side of successful temporal lobectomy. The concordance of MRS with the side of successful temporal lobectomy was intermediate (0.75). When the results of functional and morphologic imaging were combined, no significant differences were found between the rates of agreement of FDG-PET/MRI and MRS/MRI with EEG (0.80 vs 0.68; P=0.50) and with the side of successful temporal lobectomy (0.87 vs 0.92; P=0.50) in TLE cases. However, MRS/MRI showed significantly more lateralized temporal lobe abnormalities in non-temporal lobe epilepsy cases than FDG-PET/MRI (0.90 vs. 0.17; P<0.01). Although FDG-PET seems to be the most reliable and stable method for this purpose, we conclude that in TLE cases it may be justified to perform MRS, which is less expensive, faster and has no radiation exposure, in combination with MRI before FDG-PET, since FDG-PET offers little additional diagnostic information if MRS and MRI indicate the same seizure focus lateralization.

Detection of mesial temporal lobe hypoperfusion in patients with temporal lobe epilepsy by use of arterial spin labeled perfusion MR imaging.

BACKGROUND AND PURPOSE: Interictal hypometabolism has lateralizing value in cases of temporal lobe epilepsy and positive predictive value for seizure-free outcome after surgery to treat epilepsy. Alterations in regional cerebral metabolism can also be inferred from measurements of regional cerebral perfusion. The purpose of this study was to determine the feasibility of detecting cerebral blood flow (CBF) asymmetries in the mesial temporal lobes using continuous arterial spin labeling perfusion MR imaging, which is a noninvasive method for calculating regional CBF. METHODS: Twelve patients with medically refractory temporal lobe epilepsy who underwent preoperative evaluation for temporal lobectomy and 12 normal control participants were studied retrospectively. Absolute and normalized mesial temporal CBF measurements were compared between the patient and control groups. Lateralization based on a perfusion asymmetry index was compared with metabolic ((18)[F]-fluorodeoxyglucose positron emission tomography) and hippocampal volumetric asymmetry indices and with clinical lateralization. RESULTS: Mesial temporal CBF was more asymmetric in patients with temporal lobe epilepsy than in normal control participants, although asymmetric mesial temporal CBF was also found in normal participants, with the left side dominant. Ipsilateral mesial temporal CBF was significantly decreased compared with contralateral mesial temporal CBF in patients with temporal lobe epilepsy. Global CBF measurements were significantly decreased in patients compared with control participants. Asymmetry in mesial temporal blood flow in patients persisted after normalization to global CBF. Lateralization using continuous arterial spin labeling perfusion MR imaging asymmetry index significantly correlated with lateralization based on (18)[F]-fluorodeoxyglucose positron emission tomography hypometabolism, hippocampal volumes, and clinical evaluation. CONCLUSION: Continuous arterial spin labeling perfusion MR imaging can detect interictal asymmetries in mesial temporal lobe perfusion in patients with temporal lobe epilepsy. This technique is readily combined with routine structural assessment and potentially offers an inexpensive and noninvasive means of screening for asymmetries in interictal mesial temporal lobe function.

Comparison of visual and ROI-based brain tumour grading using 18F-FDG PET: ROC analyses.

Several studies have suggested that the use of simple visual interpretation criteria for the investigation of brain tumours by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) might be similarly or even more accurate than quantitative or semi-quantitative approaches. We investigated this hypothesis by comparing the accuracy of FDG-PET brain tumour grading using a proposed six-step visual grading scale (VGS; applied by three independent observers unaware of the clinical history and the results of histopathology) and three different region of interest (ROI) ratios (maximal tumour uptake compared with contralateral tissue [Tu/Tis], grey matter [Tu/GM] and white matter [Tu/WM]). The patient population comprised 47 patients suffering from 17 benign (7 gliomas of grade II, 10 non-gliomatous tumours) and 30 malignant (23 gliomas of grade III-IV, 7 non-gliomatous tumours) tumours. The VGS results were highly correlated with the different ROI ratios (R=0.91 for Tu/GM, R=0.82 for Tu/WM, and R=0.79 for Tu/Tis), and high inter-observer agreement was achieved (kappa=0.63, 0.76 and 0.81 for the three observers). The mean ROI ratios and VGS readings of gliomatous and non-gliomatous lesions were not significantly different. For all measures, high-grade lesions showed significantly higher FDG uptake than low-grade lesions (P<0.005 to P<0.0001, depending on the measure used). Nominal logistic regressions and receiver operating characteristic (ROC) analyses were used to calculate cut-off values to differentiate low- from high-grade lesions. The predicted (by ROC) diagnostic sensitivity/specificity of the different tests (cut-off ratios shown in parentheses) were: Tu/GM: 0.87/0.85 (0.7), Tu/WM: 0.93/0.80 (1.3). Tu/Tis: 0.80/0.80 (0.8) and VGS: 0.84/0.95 (uptake < GM, but >> WM). The VGS yielded the highest Az (+/-SE) value (i.e. area under the ROC curve as a measure of predicted accuracy), 0.97+/-0.03, which showed a strong tendency towards being significantly greater than the Az of Tu/Tis (0.88+/-0.06; P=0.06). Tu/GM (0.92+/-0.04) and Tu/WM (0.91+/-0.05) reached intermediate Az values (not significantly different from any other value). We conclude that the VGS represents a measure at least as accurate as the Tu/GM and Tu/WM ratios. The Tu/Tis ratio is less valid owing to the high dependence on the location of the lesion. Depending on the investigator's experience and the structure of the lesions, the easily used VGS might be the most favourable grading criterion.

Simplified quantification of dopamine transporters in humans using [99mTc]TRODAT-1 and single-photon emission tomography.

Quantification of dopamine transporters (DAT) using [99mTc]TRODAT-1 and single-photon emission tomography (SPET) requires full kinetic modeling of the data, using complex and invasive arterial blood sampling to provide an input function to the model. We have shown previously that a simpler reference tissue model provides accurate quantitative results, using a reference region devoid of DAT as the input to the model and thereby obviating the need for blood sampling. We now extend this work into humans, and develop further simplifications to make the imaging protocol much more practical as a routine procedure. Fourteen healthy subjects (age 29.8 +/- 8.4 years, range 18.7-45.5 years) underwent dynamic SPET for 6 h following injection of 752 +/- 28 MBq [99mTc]TRODAT-1. The kinetic data were analyzed using nonlinear regression analysis (NLRA) and Logan-Patlak graphical analysis. In addition, simple average ratios of striatal-to-background counts were obtained for three 1-h periods (3-4 h, 4-5 h, 5-6 h), and compared against the kinetic models. All methods gave an index of specific binding, proportional to the binding potential, known as the distribution volume ratio (DVR). The reference tissue NLRA gave mean values of k3=0.013 +/- 0.003 min(-1), k4=0.011 +/- 0.002 min(-1), and DVR=2.29 +/- 0.17. Graphical analysis gave a value of DVR=2.28 +/- 0. 16, and the three ratio values of DVR were: 3-4 h, 2.18 +/- 0.15; 4-5 h, 2.34 +/- 0.13; and 5-6 h, 2.46 +/- 0.19. Graphical analysis was highly correlated with NLRA (R2=0.91, slope=0.90 +/- 0.08). The ratio methods correlated well with NLRA (3-4 h, R2=0.71, slope= 0.73 +/- 0.13; 4-5 h, R2=0.86, slope=0.73 +/- 0.09; 5-6 h, R2=0.80, slope=1.00 +/- 0.15), and also with graphical analysis (3-4 h, R2=0.65, slope=0.74 +/- 0.16; 4-5 h, R2=0.85, slope=0.78 +/- 0.09; 5-6 h, R2=0.88, slope=1.11 +/- 0.12). The optimum equilibrium time point for obtaining a simple ratio was approximately 4.5-5.5 h. In conclusion, the simple ratio techniques for obtaining a quantitative measure of specific binding correlated well with the reference tissue kinetic models, using both NLRA and graphical analysis. The optimum time for obtaining a ratio appeared to be in the range 4.5-5.5 h. Earlier time points, while still relatively accurate, had a lower sensitivity and may not be optimized for measuring small changes in DAT concentrations.