Prognostic biomarkers in prodromal α-synucleinopathies: DAT binding and REM sleep without atonia.

BACKGROUND: Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a prodromal state of clinical α-synucleinopathies such as Parkinson's disease and Lewy body dementia. The lead-time until conversion is unknown. The most reliable marker of progression is reduced striatal dopamine transporter (DAT) binding, but low availability of imaging facilities limits general use. Our prospective observational study aimed to relate metrics of REM sleep without atonia (RWA)-a hallmark of RBD-to DAT-binding ratios in a large, homogeneous sample of patients with RBD to explore the utility of RWA as a marker of progression in prodromal α-synucleinopathies. METHODS: DAT single-photon emission CT (SPECT) and video polysomnography (vPSG) were performed in 221 consecutive patients with clinically suspected RBD. RESULTS: vPSG confirmed RBD in 176 patients (162 iRBD, 14 phenoconverted, 45 non-synucleinopathies). Specific DAT-binding ratios differed significantly between groups, but showed considerable overlap. Most RWA metrics correlated significantly with DAT-SPECT ratios (eg, Montreal tonic vs most-affected-region: r=-0.525; p<0.001). In patients taking serotonergic/noradrenergic antidepressants or dopaminergic substances or with recent alcohol abuse, correlations were weaker, suggesting a confounding influence, unlike other possible confounders such as beta-blocker use or comorbid sleep apnoea. CONCLUSIONS: In this large single-centre prospective observational study, we found evidence that DAT-binding ratios in patients with iRBD can be used to describe a continuum in the neurodegenerative process. Overlap with non-synucleinopathies and clinical α-synucleinopathies, however, precludes the use of DAT-binding ratios as a precise diagnostic marker. The parallel course of RWA metrics and DAT-binding ratios suggests in addition to existing data that RWA, part of the routine diagnostic workup in these patients, may represent a marker of progression. Based on our findings, we suggest ranges of RWA values to estimate whether patients are in an early, medium or advanced state within the prodromal phase of α-synucleinopathies, providing them with important information about time until possible conversion.

Benefit of Static FET PET in Pretreated Pediatric Brain Tumor Patients with Equivocal Conventional MRI Results.

BACKGROUND: MRI has shortcomings in differentiation between tumor tissue and post-therapeutic changes in pretreated brain tumor patients. PATIENTS: We assessed 22 static FET-PET/CT-scans of 17 pediatric patients (median age 12 years, range 2-16 years, ependymoma n=4, medulloblastoma n=4, low-grade glioma n=6, high-grade glioma n=3, germ cell tumor n=1, choroid plexus tumor n=1, median follow-up: 112 months) with multimodal treatment. METHOD: FET-PET/CT-scans were analyzed visually by 3 independent nuclear medicine physicians. Additionally quantitative FET-Uptake for each lesion was determined by calculating standardized uptake values (SUVmaxT/SUVmeanB, SUVmeanT/SUVmeanB). Histology or clinical follow-up served as reference. RESULTS: Static FET-PET/CT reliably distinguished between tumor tissue and post-therapeutic changes in 16 out of 17 patients. It identified correctly vital tumor tissue in 13 patients and post-therapeutic changes in 3 patients. SUV-based analyses were less sensitive than visual analyses. Except from a choroid plexus carcinoma, all tumor entities showed increased FET-uptake. DISCUSSION: Our study comprises a limited number of patients but results corroborate the ability of FET to detect different brain tumor entities in pediatric patients and discriminate between residual/recurrent tumor and post-therapeutic changes. CONCLUSIONS: We observed a clear benefit from additional static FET-PET/CT-scans when conventional MRI identified equivocal lesions in pretreated pediatric brain tumor patients. These results warrant prospective studies that should include dynamic scans.

Patient Preferences for Coronary CT Angiography with Stress Perfusion, SPECT, or Invasive Coronary Angiography.

Background Patient preference is pivotal for widespread adoption of tests in clinical practice. Patient preferences for invasive versus other noninvasive tests for coronary artery disease are not known. Purpose To compare patient acceptance and preferences for noninvasive and invasive cardiac imaging in North and South America, Asia, and Europe. Materials and Methods This was a prospective 16-center trial in 381 study participants undergoing coronary CT angiography with stress perfusion, SPECT, and invasive coronary angiography (ICA). Patient preferences were collected by using a previously validated questionnaire translated into eight languages. Responses were converted to ordinal scales and were modeled with generalized linear mixed models. Results In patients in whom at least one test was associated with pain, CT and SPECT showed reduced median pain levels, reported on 0-100 visual analog scales, from 20 for ICA (interquartile range [IQR], 4-50) to 6 for CT (IQR, 0-27.5) and 5 for SPECT (IQR, 0-25) (P < .001). Patients from Asia reported significantly more pain than patients from other continents for ICA (median, 25; IQR, 10-50; P = .01), CT (median, 10; IQR, 0-30; P = .02), and SPECT (median, 7; IQR, 0-28; P = .03). Satisfaction with preparation differed by continent and test (P = .01), with patients from Asia reporting generally lower ratings. Patients from North America had greater percentages of "very high" or "high" satisfaction than patients from other continents for ICA (96% vs 82%, respectively; P < .001) and SPECT (95% vs 79%, respectively; P = .04) but not for CT (89% vs 86%, respectively; P = .70). Among all patients, CT was preferred by 54% of patients, compared with 18% for SPECT and 28% for ICA (P < .001). Conclusion For cardiac imaging, patients generally favored CT angiography with stress perfusion, while study participants from Asia generally reported lowest satisfaction. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Woodard and Nguyen in this issue.

Coronary Artery Disease: Analysis of Diagnostic Performance of CT Perfusion and MR Perfusion Imaging in Comparison with Quantitative Coronary Angiography and SPECT-Multicenter Prospective Trial.

Purpose To compare the diagnostic performance of stress myocardial computed tomography (CT) perfusion with that of stress myocardial magnetic resonance (MR) perfusion imaging in the detection of coronary artery disease (CAD). Materials and Methods All patients gave written informed consent prior to inclusion in this institutional review board-approved study. This two-center substudy of the prospective Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-Detector Row Computed Tomography (CORE320) multicenter trial included 92 patients (mean age, 63.1 years ± 8.1 [standard deviation]; 73% male). All patients underwent perfusion CT and perfusion MR imaging with either adenosine or regadenoson stress. The predefined reference standards were combined quantitative coronary angiography (QCA) and single-photon emission CT (SPECT) or QCA alone. Results from coronary CT angiography were not included, and diagnostic performance was evaluated with the Mantel-Haenszel test stratified by disease status. Results The prevalence of CAD was 39% (36 of 92) according to QCA and SPECT and 64% (59 of 92) according to QCA alone. When compared with QCA and SPECT, per-patient diagnostic accuracy of perfusion CT and perfusion MR imaging was 63% (58 of 92) and 75% (69 of 92), respectively (P = .11); sensitivity was 92% (33 of 36) and 83% (30 of 36), respectively (P = .45); and specificity was 45% (25 of 56) and 70% (39 of 56), respectively (P < .01). When compared with QCA alone, diagnostic accuracy of CT perfusion and MR perfusion imaging was 82% (75 of 92) and 74% (68 of 92), respectively (P = .27); sensitivity was 90% (53 of 59) and 69% (41 of 59), respectively (P < .01); and specificity was 67% (22 of 33) and 82% (27 of 33), respectively (P = .27). Conclusion This multicenter study shows that the diagnostic performance of perfusion CT is similar to that of perfusion MR imaging in the detection of CAD. © RSNA, 2017 Online supplemental material is available for this article.

The relationship between structural MRI, FDG-PET, and memory in temporal lobe epilepsy: Preliminary results.

Structural and metabolic abnormalities of the temporal lobe are frequently found in temporal lobe epilepsy (TLE). In the present retrospective study, we investigated whether structural abnormalities evident in magnetic resonance imaging (MRI) and hypometabolism evident in [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) independently influence verbal and nonverbal learning and delayed memory in patients with TLE. Sixty-eight patients with refractory unilateral TLE (35 left TLE, 33 right TLE) were divided into three groups: (1) no evidence of pathology in either MRI or FDG-PET studies (MRI-/PET-, n=15), (2) temporal FDG-PET determined hypometabolism with normal MRI findings (MRI-/PET+, n=21), and (3) evidence of temporal abnormalities in both MRI and FDG-PET studies (MRI+/PET+, n=32). A fourth group (MRI+/PET-, n=4) was too small for further statistical analysis and could not be included. Patients with MRI+/PET+ showed worse verbal memory than patients with MRI-/PET- (p<0.01), regardless of side of seizure focus. Verbal memory performance of patients with MRI-/PET+ was located between patients with MRI+/PET+ and MRI-/PET-, although group differences did not achieve statistical significance (ps>0.1). No group differences were found for nonverbal memory (p=0.27). Our results may suggest an interactive negative effect of metabolic and structural temporal lobe abnormalities on verbal memory. Still, our results are preliminary and need further validation by studies involving larger patient groups and up-to date quantitative imaging analysis methods.

Chronic alcohol intake abolishes the relationship between dopamine synthesis capacity and learning signals in the ventral striatum.

Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such 'hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N = 27). All participants also underwent 6-[(18) F]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation by RPEs nor striatal dopamine synthesis capacity differed between groups. However, ventral striatal coding of RPEs correlated inversely with craving in patients. Furthermore, we found a negative correlation between ventral striatal coding of RPEs and dopamine synthesis capacity in healthy controls, but not in alcohol-dependent patients. Moderator analyses showed that the magnitude of the association between dopamine synthesis capacity and RPE coding depended on the amount of chronic, habitual alcohol intake. Despite the relatively small sample size, a power analysis supports the reported results. Using a multimodal imaging approach, this study suggests that dopaminergic modulation of neural learning signals is disrupted in alcohol dependence in proportion to long-term alcohol intake of patients. Alcohol intake may perpetuate itself by interfering with dopaminergic modulation of neural learning signals in the ventral striatum, thus increasing craving for habitual drug intake.

(18)F-FET-PET guided surgical biopsy and resection in children and adolescence with brain tumors.

PURPOSE: MRI alone has its limitations for target selection in biopsy or resection in newly diagnosed and pretreated pediatric brain tumor patients. (18)F-FET-PET imaging is considered to identify metabolically active tumor tissue and to differentiate it from therapy-associated changes. We retrospectively analyzed our experience with (18)F-FET-PET in targeted surgical interventions for pediatric brain tumors. METHODS: In 26 cases with lesions suspicious of a growing brain tumor on MRI, either newly diagnosed or after antitumoral treatment led to (18)F-FET-PET imaging for target selection prior to stereotactic biopsy, navigated open biopsy or navigated microsurgical tumor resection. Indications for (18)F-FET-PET imaging were visualization of metabolic active tumor tissue within diffuse tumors or pretreated lesions as well as depicting their extent. RESULTS: (18)F-FET-PET integration in surgery was feasible in all patients using stereotaxy or neuronavigation. Sensitivity for tumor detection was 20/24. (18)F-FET-PET was false positive in two pretreated patients. CONCLUSION: (18)F-FET-PET imaging is helpful for target selection and can be integrated in surgical guidance. (18)F-FET-PET image-guided surgical targeting yielded histological diagnosis with decent specificity and high sensitivity in our cohort of pediatric brain tumor patients. Our results warrant further evaluation of (18)F-FET-PET imaging for surgical guidance.

Ventral striatal prediction error signaling is associated with dopamine synthesis capacity and fluid intelligence.

Fluid intelligence represents the capacity for flexible problem solving and rapid behavioral adaptation. Rewards drive flexible behavioral adaptation, in part via a teaching signal expressed as reward prediction errors in the ventral striatum, which has been associated with phasic dopamine release in animal studies. We examined a sample of 28 healthy male adults using multimodal imaging and biological parametric mapping with (1) functional magnetic resonance imaging during a reversal learning task and (2) in a subsample of 17 subjects also with positron emission tomography using 6-[(18) F]fluoro-L-DOPA to assess dopamine synthesis capacity. Fluid intelligence was measured using a battery of nine standard neuropsychological tests. Ventral striatal BOLD correlates of reward prediction errors were positively correlated with fluid intelligence and, in the right ventral striatum, also inversely correlated with dopamine synthesis capacity (FDOPA K inapp). When exploring aspects of fluid intelligence, we observed that prediction error signaling correlates with complex attention and reasoning. These findings indicate that individual differences in the capacity for flexible problem solving relate to ventral striatal activation during reward-related learning, which in turn proved to be inversely associated with ventral striatal dopamine synthesis capacity.

Impact of subcortical white matter lesions on dopamine transporter SPECT.

Subcortical arteriosclerotic encephalopathy (SAE) can affect the nigrostriatal system and presumably cause vascular parkinsonism (VP). However, in patients with SAE, the differentiation of VP from idiopathic Parkinson's disease (IPS) is challenging. The aim of the present study was to examine the striatal dopamine transporter (DAT) density in patients with parkinsonism and SAE. Fifteen consecutive patients with parkinsonian symptoms displayed SAE, as detected by magnetic resonance imaging (MRI). Fifteen retrospectively chosen, matched patients with diagnosis of IPS without any abnormalities in MRI served as a reference group. DAT SPECT was performed using the tracer ¹²³I-FP-CIT. Scans were acquired on a triple-head SPECT system (Multispect 3, Siemens) and analysed using the investigator-independent BRASS™ software (HERMES). In the SAE group, a DAT deficit was observed in 9/15 patients. In contrast, all patients from the IPS group showed a reduced DAT binding (p = 0.008). The specific binding ratios (BR) of putamen contralateral to the side of the more affected limb versus occipital lobe were in trend higher in patients with SAE versus patients in the IPS-group (p = 0.053). Indices for putaminal asymmetry (p = 0.036) and asymmetry caudate-to-putamen (p = 0.026) as well as the ratio caudate-to-putamen (p = 0.048) were significantly higher in IPS patients having no SAE. DAT deficit was less pronounced in patients with SAE and parkinsonism than in patients with IPS without any abnormalities in the MRI. A potential role of DAT SPECT in the differential diagnosis of VP and IPS requires more assessments within prospective studies.

Decline in prefrontal catecholamine synthesis explains age-related changes in cognitive speed beyond regional grey matter atrophy.

PURPOSE: Age-related decline in cognitive speed has been associated with prefrontal dopamine D1 receptor availability, but the contribution of presynaptic dopamine and noradrenaline innervation to age-related changes in cognition is unknown. METHODS: In a group of 16 healthy participants aged 22-61 years, we used PET and the radioligand FDOPA to measure catecholamine synthesis capacity (K (in) (app); millilitres per gram per minute) and the digit symbol substitution test to measure cognitive speed, a component of fluid IQ. RESULTS: Cognitive speed was associated with the magnitude of K (in) (app) in the prefrontal cortex (p < 0.0005). Both cognitive speed (p = 0.003) and FDOPA K (in) (app) (p < 0.0005) declined with age, both in a standard voxel-wise analysis and in a volume-of-interest analysis with partial volume correction, and the correlation between cognitive speed and K (in) (app) remained significant beyond the effects of age (p = 0.047). MR-based segmentation revealed that these age-related declines were not attributable to age-related alterations in grey matter density. CONCLUSION: Our findings indicate that age-related changes in the capacity of the prefrontal cortex to synthesize catecholamines, irrespective of cortical atrophy, may underlie age-related decline in cognitive speed.

No correlation of substantia nigra echogenicity and nigrostriatal degradation in Parkinson's disease.

BACKGROUND: Substantia nigra hyperechogenicity assessed by transcranial sonography is a typical finding in up to 90% of patients with idiopathic Parkinson's disease, although its value as a surrogate marker for disease progression in Parkinson's disease is controversial. (123) I-FP-CIT-single photon emission computed tomography (SPECT) represents an established paraclinical surrogate marker to quantify the nigrostriatal dopaminergic deficit in Parkinson's disease. Whereas most studies found no correlation between extent of substantia nigra echogenicity and the putaminal FP-CIT binding ratio, a more recent analysis reported opposite results. METHODS: In 92 patients with Parkinson's disease the substantia nigra echogenicity was compared with the putaminal FP-CIT binding ratio using an investigator-independent SPECT analysis protocol and with several clinical parameters. RESULTS: No correlation was found between the substantia nigra hyperechogenicity and the FP-CIT binding ratio or the disease severity. CONCLUSIONS: Substantia nigra hyperechogenicity does not reflect the degree of the nigrostriatal degeneration or the clinical state of the disease progression.

Potential impact of (68)Ga-DOTATOC PET/CT on stereotactic radiotherapy planning of meningiomas.

PURPOSE: Since meningiomas show a high expression of somatostatin receptor subtype 2, PET with (68)Ga-DOTATOC was proposed as an additional imaging modality beside CT and MRI for planning radiotherapy. We investigated the input of (68)Ga-DOTATOC-PET/CT on the definition of the "gross tumour volume" (GTV) in meningiomas, in order to assess the potential value of this method. METHODS: Prior to radiotherapy, 42 patients with meningiomas (26 f, 16 m, mean age 55) underwent MRI and (68)Ga-DOTATOC-PET/CT examinations. HISTORY: operated n = 24, radiotherapy n = 1, operation and radiotherapy n = 8, no treatment n = 9. PET/CT and MRI data were co-registered using a BrainLAB workstation. For comparison, the GTV was defined first under consideration of CT and MRI data, then using PET data. RESULTS: 3/42 patients were excluded from the analysis (two with negative PET results, one with an extensive tumour, not precisely delineable by MRI or PET/CT). The average GTV(CT/MRI) was 22(+/-19)cm(3); GTV(PET) was 23(+/-20)cm(3). Additional GTV, obtained as a result of PET was 9(+/-10)cm(3) and was observed in patients with osseous infiltration. In some pre-treated patients there were intratumoural areas (as identified in CT/MRI) without SR-expression (7(+/-11)cm(3)). Common GTV as obtained by both CT/MRI and PET was 15(+/-14)cm(3). The mean bi-directional difference between the GTV(CT/MRI) and GTV(PET) accounted to 16(+/-15)cm(3) (93%, p < 0.001). In a subgroup of seven patients with multiple meningiomas, PET showed a total of 19 lesions; nine of them were not recognizable by CT or MRI. CONCLUSION: (68)Ga-DOTATOC-PET enables delineation of SR-positive meningiomas and delivers additional information to both CT and MRI regarding the planning of stereotactic radiotherapy. The acquisition on a PET/CT scanner helps to estimate the relation of PET findings to anatomical structures and is especially useful for detection of osseous infiltration. (68)Ga-DOTATOC-PET also allows detection of additional lesions in patients with multiple meningiomas.

Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters.

PURPOSE: The objective of this study was to evaluate positron emission tomography (PET) using (18)F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients. METHODS: FDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n = 16; osteosarcoma (OS), n = 11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik. RESULTS: FDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population (SUV, p = 0.005; SUV2, p = 0.011) as well as in the subgroup of OS patients (SUV, p = 0.009; SUV2, p = 0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p = 0.170) or in both subgroups (EWS, p = 0.950; OS, p = 1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS. CONCLUSION: FDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment.

Continuous low-dose temozolomide and celecoxib in recurrent glioblastoma.

Even after gross tumor resection and combined radiochemotherapy, glioblastomas recur within a few months. Salvage therapy often consists of rechallenging with temozolomide in a dose-intensified schedule. Previously, low-dose metronomic temozolomide in combination with cyclo-oxigenase 2 inhibitors has had a beneficial effect as first-line treatment for glioblastoma. We report our experience with this procedure in recurrent glioblastomas after standard treatment. From June 2007 to April 2009, 28 patients with recurrent glioblastoma received continuous low-dose temozolomide of 10 mg/m(2) twice daily and 200 mg celecoxib. Before therapy the recurrent tumor was resected in 19 of 28 patients. Microvessel density (MVD) was determined by immunohistochemistry in 19 patients, and MGMT promoter methylation status, using the pyrosequencing method, was determined in 17 patients. In 14/28 patients, positron emission tomography with [F-18]-fluoroethyl)-L-tyrosine (FET-PET) was performed. Tumor progression was defined by the Macdonald criteria on MRI every 8-12 weeks or by clinical deterioration. The median time to progression was 4.2 months. Progression-free survival (PFS) after 6 months was 43%. Except for a lymphopenia in one patient, there was no grade 3 or 4 toxicity. PFS did not correlate with MVD or MGMT status. A high FET uptake correlated with tumor control after 6 months under therapy (P = 0.041, t-test). Low-dose continuous temozolomide in combination with celecoxib seems to have activity in recurrent glioblastoma without relevant toxicity. High FET uptake correlated with a better outcome under metronomic therapy.

Comparison of F-18 FET-PET with F-18 FDG-PET for biopsy planning of non-contrast-enhancing gliomas.

OBJECTIVE: The management of non-contrast-enhancing brain tumours largely depends on biopsy, which allows a differentiation of low-grade gliomas (LGG) from high-grade gliomas (HGG). The aim of this study was to compare positron emission tomography using 2-[(18)F]-fluoro-2-deoxy-D: -glucose (FDG-PET) and O-(2-[(18)F]-fluoroethyl)-L: -tyrosine (FET-PET) in terms of providing target regions for biopsies. MATERIALS AND METHODS: Fifteen consecutive patients with newly diagnosed brain tumours (n = 11) or suspected recurrence of a known LGG (n = 4), in whom MRI demonstrated no contrast enhancement, were studied by both FET-PET and FDG-PET. FET-PET, FDG-PET and MRI data were fused, and then transferred to the neurosurgical navigation system, prior to neurosurgical interventions. RESULTS: Histology showed HGG (WHO grade III) in 6/15 and LGG (WHO grade II) in 9/15 patients. FET-PET revealed an increased intratumoural tracer uptake in 8/9 LGG and in 5/6 HGG. FDG-PET depicted hypermetabolic spots in 2/9 LGG and in 4/6 HGG. In 6 patients we observed an increased intratumoural uptake of both tracers. In 4 of them, the area of highest FET accumulation in the tumour corresponded to the focus of increased FDG uptake. CONCLUSIONS: FET-PET appears to be superior to FDG-PET for biopsy planning in non-contrast-enhancing brain tumours. FDG-PET does not provide any additional information in this issue.

Combined correction of recovery effect and motion blur for SUV quantification of solitary pulmonary nodules in FDG PET/CT.

OBJECTIVE: We evaluate a fully data-driven method for the combined recovery and motion blur correction of small solitary pulmonary nodules (SPNs) in F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). METHODS: The SPN was segmented in the low-dose CT using a variable Hounsfield threshold and morphological constraints. The combined effect of limited spatial resolution and motion blur in the SPN's PET image was then modelled by an effective Gaussian point-spread function (psf). Both isotropic and non-isotropic psfs were used. To validate the method, PET/CT measurements of the NEMA/IEC spheres phantom were performed. The method was applied to 50 unselected SPNs or=30%) SUV increase in 47 SPNs (94%). CONCLUSIONS: Correction of both recovery and motion blur is mandatory for accurate SUV quantification of SPNs.

Tumour perfusion assessment during regional hyperthermia treatment: comparison of temperature probe measurement with H(2)(15)O-PET perfusion.

PURPOSE: Hyperthermia treatment might increase tumour oxygenation and perfusion, as has been reported for experimental tumours. The present study was performed to investigate this hypothesis in patients undergoing regional hyperthermia treatment. METHODS: Thirteen patients with primary or recurrent pelvic tumours were included in this study. Prior to and up to one hour after regional hyperthermia, perfusion was quantitatively determined by H(2)(15)O-PET. The fused CT-PET images were used to extract tumour time-activity curves and to identify the catheter position. Perfusion was calculated from the total tumour time-activity curves and for the time-activity curves at the catheter site. Additionally, perfusion was calculated from the temperature-time curves measured using temperature probes. RESULTS: Perfusion values calculated using H(2)(15)O-PET and those deduced from temperature probe measurements are significantly correlated with a correlation coefficient, R = 0.21. The perfusion values deduced from the temperature measured in a body cavity do not provide information about average tumour perfusion. Perfusion values deduced from the temperature are overestimated for very poorly perfused tissues and underestimated for highly perfused tissues. CONCLUSIONS: Temperature measurement during hyperthermia may allow only determination of intermediate perfusion values.

[Quality control in PET/CT systems: experiences and requirements]. / Qualitätskontrolle an PET/CT-Systemen: Erfahrungen und Erfordernisse.

Today, in most cases PET examinations are performed using PET/CT hybrid systems. While acceptance testing and routine control of the basic modalities PET and CT, respectively, are described by appropriate regulations, corresponding instructions with regard to the interface connecting both are still missing. This interface includes the adjustment of gantries and patient bed to each other as well as the energy scaling of attenuation coefficients from CT energy to 511 keV. Measurements checking the mechanical adjustment (determination of off-set parameters) are performed following manufacturer's recommendation, with a typical frequency twice a year. On a Biograph 16 (Siemens, Inc.), these measurements were systematically extended to a weekly frequency over an observation period of 10 months, supplemented by measurements with additional load to the patient bed (up to 135 kg), and different vertical bed positions. The results show, that for the construction tested additional off-set measurements for routine control extending well beyond manufacturer's recommendation are not necessary. The energy scaling of attenuation coefficients is depending on methodological aspects and software implementation, and therefore is not part of routine control. On the contrary, the development of appropriate methods for acceptance testing to assess and to determine the mechanical adjustment in all its degrees of freedom as well as the accuracy of attenuation corrected emission data is urgently needed.

Association of F18-fluoro-ethyl-tyrosin uptake and 5-aminolevulinic acid-induced fluorescence in gliomas.

PURPOSE: Malignant gliomas are highly infiltrative tumours with a fatal prognosis. F18-fluoroethyl-tyrosine (FET)-positron emission tomography (PET) often reveals a broader extension of these tumours compared with contrast-enhanced magnetic resonance imaging (MRI). Complete resection of the contrast-enhancing lesion is aspired. Fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) improved the extent of resection. In this study, we investigated whether the FET uptake correlates with the extent of resection using 5-ALA-induced fluorescence. METHODS: Thirteen patients who underwent preoperative and postoperative MRI, FET-PET and fluorescence-guided neuronavigated resection were included in this study. The areas in which intraoperative fluorescence terminated the resection were marked. After fusion of PET and MRI, the standardized uptake value (SUV) of FET related to normal brain (SUV(R)) was measured in regions of interest corresponding to resected and remaining tissue, respectively. Receiver-operating characteristic (ROC) curve analysis determined the optimal threshold of the relative SUV anticipating 5-ALA-induced fluorescence. RESULTS: During resection a vivid fluorescence was present in all patients. Histology revealed glioblastomas in 11 cases, an anaplastic astrocytoma in one case and a low-grade astrocytoma in one case. The median FET SUV(R) was higher in areas corresponding to the fluorescent tumour compared with the non-fluorescent normal brain (2.321 vs 1.142, p < 0.0001, t-test). A SUV(R) greater than 1.374 predicted the fluorescence with a sensitivity of 0.87 [95% confidence interval (CI): 0.74-0.94] and a specificity of 0.94 (CI: 0.84-0.99). The area under the ROC curve was 0.9656 (CI: 0.9364-0.9948). CONCLUSIONS: FET uptake predicts the 5-ALA-induced fluorescence in glioma patients. Thus, FET-PET provides useful information for planning glioma resection.

Brain parenchyma sonography and 123I-FP-CIT SPECT in Parkinson's disease and essential tremor.

We aimed to investigate the accuracy of transcranial brain parenchyma sonography (TCS) for differentiation between idiopathic Parkinson's disease (PD) and essential tremor (ET) in comparison to (123)I-FP-CIT SPECT (FP-CIT SPECT). Seventy-four patients, in whom PD or ET was suspected on the basis of clinical criteria, were analyzed. The echogenicity of the substantia nigra (SN) and the striatal binding of dopamine transporters (DAT) were evaluated by TCS and FP-CIT SPECT, respectively. Three patients were excluded due to an insufficient transtemporal bone window using TCS. Forty-six and 25 patients were clinically classified as PD and ET. SPECT revealed a reduced DAT binding in 42 of all 71 included patients. Thirty-six of the 42 patients with abnormal FP-CIT SPECT findings had a pathological SN hyperechogenicity, whereas TCS findings in the remaining 6 patients were normal. In 27 of 29 patients with normal SPECT findings the SN echogenicity was regular. Referring to FP-CIT SPECT, the sensitivity and specificity of TCS for detection of PD were 86 and 93%; the positive and negative predictive values were 95 and 82%, respectively. Sensitivity and specificity in detection of clinically diagnosed PD patients were 78 and 92% for TCS and 91 and 100% for FP-CIT SPECT, respectively. In patients with pathological FP-CIT SPECT and pathological TCS, the extent of SN hyperechogenicity did not correlate with the degree of reduction in dopamine transporter binding on the side opposite of the more affected limb. TCS allows a reliable differentiation of PD and ET. The TCS SN hyperechogenicity does not correlate with the extent of dopaminergic neuron degeneration.