Absolute quantitative total-body small-animal SPECT with focusing pinholes.

PURPOSE: In pinhole SPECT, attenuation of the photon flux on trajectories between source and pinholes affects quantitative accuracy of reconstructed images. Previously we introduced iterative methods that compensate for image degrading effects of detector and pinhole blurring, pinhole sensitivity and scatter for multi-pinhole SPECT. The aim of this paper is (1) to investigate the accuracy of the Chang algorithm in rodents and (2) to present a practical Chang-based method using body outline contours obtained with optical cameras. METHODS: Here we develop and experimentally validate a practical method for attenuation correction based on a Chang first-order method. This approach has the advantage that it is employed after, and therefore independently from, iterative reconstruction. Therefore, no new system matrix has to be calculated for each specific animal. Experiments with phantoms and animals were performed with a high-resolution focusing multi-pinhole SPECT system (U-SPECT-II, MILabs, The Netherlands). This SPECT system provides three additional optical camera images of the animal for each SPECT scan from which the animal contour can be estimated. RESULTS: Phantom experiments demonstrated that an average quantification error of -18.7% was reduced to -1.7% when both window-based scatter correction and Chang correction based on the body outline from optical images were applied. Without scatter and attenuation correction, quantification errors in a sacrificed rat containing sources with known activity ranged from -23.6 to -9.3%. These errors were reduced to values between -6.3 and +4.3% (with an average magnitude of 2.1%) after applying scatter and Chang attenuation correction. CONCLUSION: We conclude that the modified Chang correction based on body contour combined with window-based scatter correction is a practical method for obtaining small-animal SPECT images with high quantitative accuracy.

Men versus women on sexual brain function: prominent differences during tactile genital stimulation, but not during orgasm.

Biological differences in male and female sexuality are obvious in the behavioral domain, but the central mechanisms that might explain these behavioral gender differences remain unclear. In this study, we merged two earlier positron emission tomography data sets to enable systematic comparison of the brain responses in heterosexual men and women during sexual tactile genital (penile and clitoral) stimulation and during orgasm. Gender commonalities were most evident during orgasm, a phase which demonstrated activations in the anterior lobe of the cerebellar vermis and deep cerebellar nuclei, and deactivations in the left ventromedial and orbitofrontal cortex in both men and women. During tactile genital stimulation, deactivations in the right amygdala and left fusiform gyrus were found for both genders. Marked gender differences were seen during this phase: left fronto-parietal areas (motor cortices, somatosensory area 2 and posterior parietal cortex) were activated more in women, whereas in men, the right claustrum and ventral occipitotemporal cortex showed larger activation. The only prominent gender difference during orgasm was male-biased activation of the periaqueductal gray matter. From these results, we conclude that during the sexual act, differential brain responses across genders are principally related to the stimulatory (plateau) phase and not to the orgasmic phase itself. These results add to a better understanding of the neural underpinnings of human sexuality, which might benefit treatment of psychosexual disorders.

Phenylketonuria: High plasma phenylalanine decreases cerebral protein synthesis.

Left untreated, phenylketonuria biochemically results in high phenylalanine concentrations in blood and tissues, and clinically especially in severe mental retardation. Treatment consists of severe dietary restriction of phenylalanine with more or less normal intellectual outcome as result when started early enough. It is unclear whether treatment for life is necessary. A clear relationship between plasma phenylalanine concentrations and cerebral outcome exists, but the precise pathophysiological mechanism is not understood. In studies in mice with phenylketonuria, the cerebral protein synthesis rate is decreased when compared to controls. The aim of the present study was to determine the protein synthesis rate in relation to the plasma phenylalanine concentrations in-vivo in patients with phenylketonuria by positron emission tomography brain studies after an intravenous l-[1-(11)C]-tyrosine bolus. Results showed a significant negative relationship (R(2)=0.40, p<0.01) between plasma phenylalanine concentration and the cerebral protein synthesis rate in 19 patients with phenylketonuria. At increased plasma phenylalanine concentrations, i.e. above 600-800micromol/l, the cerebral protein synthesis rate is clearly decreased compared to lower phenylalanine concentrations. These data suggest that cerebral protein metabolism in untreated adults with phenylketonuria can be abnormal due to high plasma phenylalanine concentrations. Hence, we speculate that it is important to continue dietary treatment into adulthood, aiming at plasma phenylalanine concentrations <600-800micromol/l.

Brain activation during human male ejaculation revisited.

In a prior [O]-H2O positron emission tomographic study we reported brain regions involved in human male ejaculation. Here, we used another, more recently acquired data set to evaluate the methodological approach of this previous study, and discovered that part of the reported activation pattern was not related to ejaculation. With a new analysis of these ejaculation data, we now demonstrate ejaculation-related activations in the deep cerebellar nuclei (dentate nucleus), anterior vermis, pons, and ventrolateral thalamus, and, most importantly, ejaculation-related deactivations throughout the prefrontal cortex. This revision offers a new and more accurate insight into the brain regions involved in human male ejaculation.

Psychobiological characteristics of dissociative identity disorder: a symptom provocation study.

BACKGROUND: Dissociative identity disorder (DID) patients function as two or more identities or dissociative identity states (DIS), categorized as 'neutral identity states' (NIS) and 'traumatic identity states' (TIS). NIS inhibit access to traumatic memories thereby enabling daily life functioning. TIS have access and responses to these memories. We tested whether these DIS show different psychobiological reactions to trauma-related memory. METHODS: A symptom provocation paradigm with 11 DID patients was used in a two-by-two factorial design setting. Both NIS and TIS were exposed to a neutral and a trauma-related memory script. Three psychobiological parameters were tested: subjective ratings (emotional and sensori-motor), cardiovascular responses (heart rate, blood pressure, heart rate variability) and regional cerebral blood flow as determined with H(2)(15)O positron emission tomography. RESULTS: Psychobiological differences were found for the different DIS. Subjective and cardiovascular reactions revealed significant main and interactions effects. Regional cerebral blood flow data revealed different neural networks to be associated with different processing of the neutral and trauma-related memory script by NIS and TIS. CONCLUSIONS: Patients with DID encompass at least two different DIS. These identities involve different subjective reactions, cardiovascular responses and cerebral activation patterns to a trauma-related memory script.

Brain activation during human male ejaculation.

Brain mechanisms that control human sexual behavior in general, and ejaculation in particular, are poorly understood. We used positron emission tomography to measure increases in regional cerebral blood flow (rCBF) during ejaculation compared with sexual stimulation in heterosexual male volunteers. Manual penile stimulation was performed by the volunteer's female partner. Primary activation was found in the mesodiencephalic transition zone, including the ventral tegmental area, which is involved in a wide variety of rewarding behaviors. Parallels are drawn between ejaculation and heroin rush. Other activated mesodiencephalic structures are the midbrain lateral central tegmental field, zona incerta, subparafascicular nucleus, and the ventroposterior, midline, and intralaminar thalamic nuclei. Increased activation was also present in the lateral putamen and adjoining parts of the claustrum. Neocortical activity was only found in Brodmann areas 7/40, 18, 21, 23, and 47, exclusively on the right side. On the basis of studies in rodents, the medial preoptic area, bed nucleus of the stria terminalis, and amygdala are thought to be involved in ejaculation, but increased rCBF was not found in any of these regions. Conversely, in the amygdala and adjacent entorhinal cortex, a decrease in activation was observed. Remarkably strong rCBF increases were observed in the cerebellum. These findings corroborate the recent notion that the cerebellum plays an important role in emotional processing. The present study for the first time provides insight into which regions in the human brain play a primary role in ejaculation, and the results might have important implications for our understanding of how human ejaculation is brought about, and for our ability to improve sexual function and satisfaction in men.

rCBF differences between panic disorder patients and control subjects during anticipatory anxiety and rest.

BACKGROUND: Our goal was to identify brain structures involved in anticipatory anxiety in panic disorder (PD) patients compared to control subjects. METHODS: Seventeen PD patients and 21 healthy control subjects were studied with H(2)(15)O positron emission tomography scan, before and after a pentagastrin challenge. RESULTS: During anticipatory anxiety we found hypoactivity in the precentral gyrus, the inferior frontal gyrus, the right amygdala, and the anterior insula in PD patients compared to control subjects. Hyperactivity in patients compared to control subjects was observed in the parahippocampal gyrus, the superior temporal lobe, the hypothalamus, the anterior cingulate gyrus, and the midbrain. After the challenge, the patients showed decreases compared to the control subjects in the precentral gyrus, the inferior frontal gyrus, and the anterior insula. Regions of increased activity in the patients compared to the control subjects were the parahippocampal gyrus, the superior temporal lobe, the anterior cingulate gyrus, and the midbrain. CONCLUSIONS: The pattern of regional cerebral blood flow activations and deactivations we observed both before and after the pentagastrin challenge was the same, although different in intensity. During anticipatory anxiety more voxels were (de)activated than during rest after the challenge.

Activations of "motor" and other non-language structures during sentence comprehension.

In this paper we report the results of an experiment in which subjects read syntactically unambiguous and ambiguous sentences which were disambiguated after several words to the less likely possibility. Understanding such sentences involves building an initial structure, inhibiting the non-preferred structure, detecting that later input is incompatible with the initial structure, and reactivating the alternative structure. The ambiguous sentences activated four areas more than the unambiguous sentences. These areas are the left inferior frontal gyrus (IFG), the right basal ganglia (BG), the right posterior dorsal cerebellum (CB) and the left median superior frontal gyrus (SFG). The left IFG is normally activated when syntactic processing complexity is increased and probably supports that function in the current study as well. We discuss four hypotheses concerning how these areas may support comprehension of syntactically ambiguous sentences. (1) The left IFG, right CB and BG could support articulatory rehearsal used to support the processing of ambiguous sentences. This seems unlikely since the activation pattern associated with articulatory rehearsal in other studies is not similar to that seen here. (2) The CB acts as an error detector in motor processing. Error detection is important for recognizing that the wrong sentence structure has been chosen initially. (3) The BG acts to select and sequence movements in the motor domain and in cognitive domains may serve to inhibit competing and completed plans which is not unlike inhibiting the initially non-preferred structure or "unchoosing" the initial choice when incompatible syntactic input is received. (4) The left median SFG is relevant for the evaluation of plausibility. Evaluating the plausibility of the two possibilities provides an important basis for choosing between them. The notion of the use of domain general cognitive processes to support a linguistic process is in line with recent suggestions that the a given area may subserve a specific cognitive task because it carries out an appropriate sort of computation rather than because it supports a specific cognitive domain.

Phenylketonuria: reduced tyrosine brain influx relates to reduced cerebral protein synthesis.

BACKGROUND: In phenylketonuria (PKU), elevated blood phenylalanine (Phe) concentrations are considered to impair transport of large neutral amino acids (LNAAs) from blood to brain. This impairment is believed to underlie cognitive deficits in PKU via different mechanisms, including reduced cerebral protein synthesis. In this study, we investigated the hypothesis that impaired LNAA influx relates to reduced cerebral protein synthesis. METHODS: Using positron emission tomography, L-[1-11C]-tyrosine (11C-Tyr) brain influx and incorporation into cerebral protein were studied in 16 PKU patients (median age 24, range 16 - 47 years), most of whom were early and continuously treated. Data were analyzed by regression analyses, using either 11C-Tyr brain influx or 11C-Tyr cerebral protein incorporation as outcome variable. Predictor variables were baseline plasma Phe concentration, Phe tolerance, age, and 11C-Tyr brain efflux. For the modelling of cerebral protein incorporation, 11C-Tyr brain influx was added as a predictor variable. RESULTS: 11C-Tyr brain influx was inversely associated with plasma Phe concentrations (median 512, range 233 - 1362 µmol/L; delta adjusted R2=0.571, p=0.013). In addition, 11C-Tyr brain influx was positively associated with 11C-Tyr brain efflux (delta adjusted R2=0.098, p=0.041). Cerebral protein incorporation was positively associated with 11C-Tyr brain influx (adjusted R2=0.567, p<0.001). All additional associations between predictor and outcome variables were statistically nonsignificant. CONCLUSIONS: Our data favour the hypothesis that an elevated concentration of Phe in blood reduces cerebral protein synthesis by impairing LNAA transport from blood to brain. Considering the importance of cerebral protein synthesis for adequate brain development and functioning, our results support the notion that PKU treatment be continued in adulthood. Future studies investigating the effects of impaired LNAA transport on cerebral protein synthesis in more detail are indicated.

Left ventricular volume assessment by planar radionuclide ventriculography evaluated by MRI.

BACKGROUND: Assessment of left ventricular (LV) ejection fraction (LVEF) and LV volume are essential for the evaluation of prognosis in cardiac disease. LVEF and LV volumes can be measured with several imaging modalities, such as magnetic resonance imaging (MRI) or computed tomography; however, these are relatively expensive and time consuming. In contrast, planar radionuclide ventriculography (PRV) for LVEF assessment is a cost-effective, fast, and reliable technique, but PRV for LV volumes calculation is less common. AIM: Evaluation of a new hybrid geometrical count-based method (HGCBM) in comparison with two count-based methods (CBMs) and a geometrical method (GM) for the calculation of LV volumes with PRV using MRI as reference. METHODS: Thirty cardiac patients underwent routine PRV with a standard dose of 500 MBq of Tc-pertechnetate and additional cardiac MRI as reference method. LV volumes of PRV data were calculated by four different methods. The CBMs and GM are based on the assumption that the shape of the LV can be approximated by an ellipsoid or sphere, and the new HGCBM extracts the volume from the projected count rates themselves. RESULTS: All methods underestimated the LV volumes as compared with the MRI-measured volumes. The difference (mean+/-SD) of end-diastolic volume (EDV) between PRV and MRI was 33+/-23 ml for GM, 12+/-26 ml for HGCBM, 50+/-38 ml for CBM1, and 13+/-40 ml for CBM2. The correlation coefficients for EDV between PRV methods and MRI were r = 0.90 for GM and r = 0.85 for HGCBM. The CBMs showed poor correlation r = 0.64 with the MRI data and a high SD. The difference of end-systolic volume (ESV) between PRV and MRI was 23+/-19 ml for GM, 9+/-22 ml for HGCBM, 29+/-29 ml for CBM1, and 9+/-28 ml for CBM2. The correlation coefficients for ESV between PRV methods and MRI were r = 0.955 for GM and r = 0.914 for HGCBM, r = 0.85 for CBM1 and CBM2. Although GM showed a slightly higher correlation than HGCBM, the difference of EDV and ESV between PRV and MRI was much higher for GM in comparison with HGCBM. Both CBMs showed poor agreement with MRI data. CONCLUSION: PRV using the new HGCMB method in comparison with other methods is an easy and accurate method to determine LV volumes. However, all methods underestimate ESV and EDV slightly as compared with MRI.

The diagnostic value of 124I-PET in patients with differentiated thyroid cancer.

BACKGROUND: The purpose of this prospective study was to evaluate the clinical diagnostic value of iodine-124 (124I)-positron emission tomography (PET) in patients with advanced differentiated thyroid carcinoma (DTC) and to compare the 124I-PET imaging results with the 131I whole-body scan (WBS). MATERIALS AND METHODS: Twenty patients with histologically proven advanced DTC (including T4, extra-nodal tumour growth, or distant metastases) underwent diagnostic 131I-WBS, 124I-PET scan, and post-treatment 131I-WBS 4 months after ablation. The findings on the 124I-PET were compared with the findings on the diagnostic and post-therapeutic 131I-WBS and were also correlated with radiologic and/or cytological investigations. RESULTS: 124 I-PET vs diagnostic 131 I-WBS. Eleven patients showed uptake on the 124I-PET. Only 3 of these 11 patients also showed uptake on the diagnostic 131I scan, but the uptake was more clearly visible and the abnormalities were more extensive on the 124I-PET. 124 I-PET vs post-treatment 131 I-WBS. Eleven patients showed uptake on the 124I-PET, which was also visible on the post-treatment scan in nine patients; in the other two patients, no uptake was observed on the post-treatment scan and no anatomical localisation could be confirmed. Two patients showed only uptake on the post-treatment scan without uptake on the 124I-PET: in one, the uptake was confirmed by MRI, and in the other, no anatomical localisation was found. In seven patients, no uptake was observed on both the scans. CONCLUSION: 124I-PET proved to be a superior diagnostic tool as compared to low-dose diagnostic 131I scans and adequately predicted findings on subsequent high-dose post-treatment 131I scans.

Methylphenidate-induced activation of the anterior cingulate but not the striatum: a [15O]H2O PET study in healthy volunteers.

The dopaminergic system has been implicated in the pathogenesis and treatment of a variety of neuropsychiatric disorders, such as schizophrenia, depression, and addiction. (Dys)function of the dopaminergic system may be studied by combining [15O]H2O PET with a dopaminergic drug challenge. In this pilot study we investigated the suitability of the dopamine reuptake blocker methylphenidate (MP) as a dopaminergic probe. Measurements of regional cerebral blood flow (rCBF) were made at 10 and 30 min after placebo and MP (0.25 mg/kg) injection to seven healthy volunteers. During scanning the behavioral condition of the subjects was standardized using a continuous performance task. Growth hormone levels were assessed and subjective ratings were obtained. MP significantly elevated growth hormone levels. After receiving MP, the subjective experience varied from neutral to highly pleasurable. Ten minutes after MP administration, significant relative increases in rCBF were found in the rostral anterior cingulate (AC), temporal poles, and the supplementary motor area. Significant reductions were seen in the superior temporal gyri, right medial frontal gyrus, and right inferior parietal cortex. At 30 min after MP administration, increases were seen in the AC, temporal pole, and right cerebellum. No changes were observed in the striatum. The activation in the right rostral AC was significantly higher in the subjects with the highest euphoria scores compared to the subjects with minimal MP-induced changes in euphoria. We suggest that the combined MP challenge with functional imaging, as described in our study, may be a useful tool to study the functional integrity of the dopaminergic system in psychiatric disorders.

Positron emission tomography: the conceptual idea using a multidisciplinary approach.

Positron emission tomography (PET) is a method for quantitatively measuring biochemical and physiological processes in vivo by using radiopharmaceuticals labeled with positron-emitting radionuclides such as 11C, 13N, 15O, and 18F and by measuring the annihilation radiation using a coincidence technique. This technique is also used for measurement of the pharmacokinetics of labeled drugs and measurement of the effects of drugs on metabolism. Deviations from normal metabolism can be measured and insight into biological processes responsible for diseases can be obtained.