FDG-PET/MRI with high-resolution DWI characterises the distinct phenotypes of endometrial cancer.

AIM: To evaluate the capability of integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG)-positron-emission tomography (PET)/magnetic resonance imaging (MRI) to characterise the distinct phenotypes of endometrial cancer. MATERIALS AND METHODS: Thirty-one patients with endometrial cancer (23 with type I, including 17 G1 and six G2 endometrioid adenocarcinomas, and eight with type II, including three G3 endometrioid adenocarcinomas, two carcinosarcomas, and three serous carcinomas) underwent pretreatment FDG-PET/MRI with simultaneous reduced field-of-view diffusion-weighted imaging (DWI). The standardised uptake value (SUV), apparent diffusion coefficient (ADC), and SUV-to-ADC ratio were compared between low-risk (type I and stage I and negative for lymph-vascular space invasion [LVSI]) and high-risk cancers. The diagnostic accuracy for discriminating the cancer phenotypes was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: The SUV was not significantly different between low-risk and high-risk endometrial cancers. High-risk cancers had a significantly lower ADC (756±232×10-6) and a greater SUV-to-ADC ratio (21.7±7.7×109) than low-risk cancers (937±154×10-6, p<0.05 and 13.1±4.1×109, p<0.005, respectively). On comparison of the area under the ROC curves (AUCs), the SUV-to-ADC ratio demonstrated the greatest diagnostic accuracy (ratio 0.83, ADC 0.72, and SUV 0.66). The AUCs for the ratios were significantly higher than those for the SUV values (p<0.05). The optimal SUV-to-ADC cut-off value of 16.9×109 for predicting high-risk cancer revealed a sensitivity of 73%, specificity of 81%, and accuracy of 77%, which was significantly higher than the accuracy for SUV. CONCLUSION: The SUV-to-ADC ratio obtained using integrated FDG-PET/MRI with high-resolution DWI reflects tumour aggressiveness including LVSI, and will be useful for lesion characterisation to decide on an appropriate therapeutic strategy for endometrial cancer.

Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

The hnRNP-Htt axis regulates necrotic cell death induced by transcriptional repression through impaired RNA splicing.

In this study, we identify signaling network of necrotic cell death induced by transcriptional repression (TRIAD) by α-amanitin (AMA), the selective RNA polymerase II inhibitor, as a model of neurodegenerative cell death. We performed genetic screen of a knockdown (KD) fly library by measuring the ratio of transformation from pupa to larva (PL ratio) under TRIAD, and selected the cell death-promoting genes. Systems biology analysis of the positive genes mapped on protein-protein interaction databases predicted the signaling network of TRIAD and the core pathway including heterogeneous nuclear ribonucleoproteins (hnRNPs) and huntingtin (Htt). RNA sequencing revealed that AMA impaired transcription and RNA splicing of Htt, which is known as an endoplasmic reticulum (ER)-stabilizing molecule. The impairment in RNA splicing and PL ratio was rescued by overexpresion of hnRNP that had been also affected by transcriptional repression. Fly genetics with suppressor or expresser of Htt and hnRNP worsened or ameliorated the decreased PL ratio by AMA, respectively. Collectively, these results suggested involvement of RNA splicing and a regulatory role of the hnRNP-Htt axis in the process of the transcriptional repression-induced necrosis.

Impaired DNA damage repair as a common feature of neurodegenerative diseases and psychiatric disorders.

Impaired DNA damage repair is a common pathological endophenotype of some types of neurodegenerative diseases, intellectual disabilities, and psychiatric diseases. Dysfunctional DNA repair and DNA damage, including DNA double-stranded breaks, are linked to transcriptional dysfunction and abnormal DNA methylation. Impaired DNA repair in neural stem cells leads to microcephaly or cerebellar ataxia. Furthermore, DNA repair defects and DNA damage in mature neurons lead to progressive cognitive impairment, which might be a common feature of Alzheimer's disease, Huntington's disease, and other polyglutamine diseases. Oxidative DNA damage and altered DNA repair gene expression are observed in GABAergic neurons in schizophrenia. These findings indicate that impaired DNA repair is a common pathological endophenotype of neurological diseases, and that DNA damage might lead to diverse disease symptoms dependent on timing and the affected cell type.

In utero gene therapy rescues microcephaly caused by Pqbp1-hypofunction in neural stem progenitor cells.

Human mutations in PQBP1, a molecule involved in transcription and splicing, result in a reduced but architecturally normal brain. Examination of a conditional Pqbp1-knockout (cKO) mouse with microcephaly failed to reveal either abnormal centrosomes or mitotic spindles, increased neurogenesis from the neural stem progenitor cell (NSPC) pool or increased cell death in vivo. Instead, we observed an increase in the length of the cell cycle, particularly for the M phase in NSPCs. Corresponding to the developmental expression of Pqbp1, the stem cell pool in vivo was decreased at E10 and remained at a low level during neurogenesis (E15) in Pqbp1-cKO mice. The expression profiles of NSPCs derived from the cKO mouse revealed significant changes in gene groups that control the M phase, including anaphase-promoting complex genes, via aberrant transcription and RNA splicing. Exogenous Apc4, a hub protein in the network of affected genes, recovered the cell cycle, proliferation, and cell phenotypes of NSPCs caused by Pqbp1-cKO. These data reveal a mechanism of brain size control based on the simple reduction of the NSPC pool by cell cycle time elongation. Finally, we demonstrated that in utero gene therapy for Pqbp1-cKO mice by intraperitoneal injection of the PQBP1-AAV vector at E10 successfully rescued microcephaly with preserved cortical structures and improved behavioral abnormalities in Pqbp1-cKO mice, opening a new strategy for treating this intractable developmental disorder.

Brain imaging for oxidative stress and mitochondrial dysfunction in neurodegenerative diseases.

Oxidative stress, one of the most probable molecular mechanisms for neuronal impairment, is reported to occur in the affected brain regions of various neurodegenerative diseases. Recently, many studies showed evidence of a link between oxidative stress or mitochondrial damage and neuronal degeneration. Basic in vitro experiments and postmortem studies demonstrated that biomarkers for oxidative damage can be observed in the pathogenic regions of the brain and the affected neurons. Model animal studies also showed oxidative damage associated with neuronal degeneration. The molecular imaging method with positron emission tomography (PET) is expected to delineate oxidatively stressed microenvironments to elucidate pathophysiological changes of the in vivo brain; however, only a few studies have successfully demonstrated enhanced stress in patients. Radioisotope copper labeled diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) may be the most promising candidate for this oxidative stress imaging. The tracer is usually known as a hypoxic tissue imaging PET probe, but the accumulation mechanism is based on the electron rich environment induced by mitochondrial impairment and/or microsomal over-reduction, and thus it is considered to represent the oxidative stress state correlated with the degree of disease severity. In this review, Cu-ATSM PET is introduced in detail from the basics to practical methods in clinical studies, as well as recent clinical studies on cerebrovascular diseases and neurodegenerative diseases. Several other PET probes are also introduced from the point of view of neuronal oxidative stress imaging. These molecular imaging methods should be promising tools to reveal oxidative injuries in various brain diseases.

Positron emission tomography radiopharmaceuticals for sex steroid hormone receptor imaging.

Understanding the expression of tumor specific receptors is important not only for tumor diagnosis but also for planning the strategy for patient treatment. Tumor receptor has been one of the most critical targets for treatment in cancer such as breast, prostate and thyroid cancers. Positron emission tomography (PET) is a part of molecular imaging techniques based on detecting the radiopharmaceuticals that can capture functional or phenotypic changes associated with pathology. The advantages of detecting tumor specific receptors by PET are its non-invasiveness, providing comprehensive information about receptor expression, avoiding the sampling errors, selecting strategy for the treatment of patients and monitoring tumor response to therapy. Hormonal therapy plays a major role in cancer treatment. Therefore, we review the PET radiopharmaceuticals for sex steroid hormone receptor imaging in this article.

Oestrogen-related tumour phenotype: positron emission tomography characterisation with ¹8F-FDG and ¹8F-FES.

This article outlines the role of 16α-[(18)F]fluoro-17ß-oestradiol ((18)F-FES) positron emission tomography (PET) combined with 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)F-FDG) in patients with oestrogen-related tumours for evaluating tumour phenotype. (18)F-FES-PET combined with (18)F-FDG is helpful in characterising the distinct phenotypic features of oestrogen-related tumours; that is, inter- and intrapatient tumour heterogeneity, which indicates its great potential as a determinant of individualised treatment and a prognostic predictor for patients with oestrogen-related tumours.

Pattern of collaterals, type of infarcts, and haemodynamic impairment in carotid artery occlusion.

BACKGROUND: In internal carotid artery (ICA) occlusion, increased oxygen extraction fraction (OEF) indicates inadequate collateral blood flow distal to the occlusion, which may be caused by poor function of collateral pathways. In ICA occlusion, the circle of Willis may be the major collateral pathway, while the collaterals through the ophthalmic artery and leptomeningeal vessels may be recruited when collateral flow through the circle of Willis is inadequate. Conversely, ischaemic lesions may affect the adequacy of collateral blood flow by reducing the metabolic demand of the brain. OBJECTIVE: To determine whether the pattern of collateral pathways and the type of infarcts are independent predictors of OEF in ICA occlusion. METHODS: We studied 42 patients with symptomatic ICA occlusion. The presence of Willisian, ophthalmic, or leptomeningeal collaterals was evaluated by conventional four vessel angiography. The infarcts on magnetic resonance imaging were categorised as territorial, border zone (external or internal), striatocapsular, lacunar, and other white matter infarcts. The value of OEF in the affected hemisphere was measured with positron emission tomography as an index of haemodynamic impairment. RESULTS: Using multivariate analysis, the presence of any ophthalmic or leptomeningeal collaterals and the absence of striatocapsular infarcts were significant and independent predictors of increased OEF. CONCLUSIONS: In patients with symptomatic ICA occlusion, the supply of collateral flow, which is affected by the pattern of collateral pathways, and the metabolic demand of the brain, which is affected by the type of infarct, may be important factors determining the severity of haemodynamic impairment.

Oxygen extraction fraction and acetazolamide reactivity in symptomatic carotid artery disease.

OBJECTIVE: It has been proposed that cerebral blood flow (CBF) response to acetazolamide may be reduced according to the degree of autoregulatory vasodilation in regions with normal oxygen extraction fraction (OEF), whereas the CBF response may be absent in regions with increased OEF where vasodilation may be maximal in response to reduced perfusion pressure. The objective of this study was to test this hypothesis. METHODS: Positron emission tomography (PET) was used to study 30 symptomatic patients with carotid artery steno-occlusive lesions. CBF at baseline and 10 minutes after an intravenous injection of 1 g acetazolamide was measured. The correlation between the change in CBF during acetazolamide administration and the baseline value of OEF in the affected hemisphere was examined. RESULTS: The baseline OEF value was inversely and non-linearly correlated with the percentage change in CBF during acetazolamide administration (R(2) = 0.25, p = 0.02). There was an upward trend of OEF with diminishing acetazolamide response below a critical level around zero response. Acetazolamide response less than 6.65% over baseline (sensitivity 100%, specificity 89%, positive predictive value 50%, negative predictive value 100%) was established as most helpful in predicting abnormally high OEF. CONCLUSIONS: The inverse, non-linear relationship between OEF and CBF response to acetazolamide suggests that these two measurements may not identify haemodynamic impairment in the same patients.

Polyglutamine diseases: a transcription disorder?

Various molecular processes including unfolded protein response, protein transport, synaptic transmission and transcription are implicated in the pathology of polyglutamine diseases caused by the expanded polyglutamine-containing proteins. More than 20 transcription-related factors have been reported to interact with disease proteins, and the pathological interaction is known to repress gene expression. The whole shape of nuclear events evoked by disease proteins is now emerging with information on these transcription-related factors and with findings on the similarity between nuclear bodies and pathological inclusion bodies. This article reviews 'transcription theory', a rapidly growing hypothesis in polyglutamine diseases.

Identification of a single nucleotide polymorphism showing no insulin-mediated suppression of the promoter activity in the human insulin receptor substrate 2 gene.

AIMS/HYPOTHESIS: To understand the transcriptional regulation and to investigate the pathological influence upon Type II (non-insulin-dependent) diabetes mellitus of insulin receptor substrate 2 ( IRS2), the 5' flanking region of the human IRS2 gene was cloned and screened in Japanese diabetic patients. METHODS: Luciferase reporter assay and electrophoretic mobility shift assay (EMSA) were combined in HepG2, Fao, RINm5F, and HeLa cells to characterise the human IRS2 promoter region. Single nucleotide polymorphisms (SNPs) were identified in Japanese Type II diabetic patients by sequencing and were genotyped. RESULTS: The proximal 2399 bp of the 5' flanking region of the human IRS2 gene was cloned. A core promoter region was extended between nucleotide positions -834 and -557 (relative to the translation initiation site). The region [(-758)AGGGGGAGGG(-749)] that appears important in the positive regulation of IRS2transcription was identified by EMSA with (32)P-labelled double-stranded oligonucleotides encompassing regions protected from DNase I digestion by nuclear extract of HepG2 cells. Two SNPs (-765 C/ T and -2062 T/ C), identified by screening Japanese Type II diabetic patients, were not associated with Type II diabetes. IRS2-driven reporter activity in the plasmid containing thymine at -765 was not suppressed by insulin when measured in Fao cells. CONCLUSION/INTERPRETATION: The 5' flanking sequence of the human IRS2 was investigated and two SNPs were identified. The SNP at -765 was suggested to be involved in the insulin-mediated regulation of the transcriptional activity of IRS2.

PQBP-1 increases vulnerability to low potassium stress and represses transcription in primary cerebellar neurons.

PQBP-1 is a polyglutamine tract binding protein implicated in transcription. We previously reported that PQBP-1 and mutant ataxin-1, product of the spinocerebellar atrophy type 1 (SCA1) causative gene, cooperatively induce cell death in culture cells. Simultaneously, we showed that mutant ataxin-1 promoted interaction between PQBP-1 and RNA polymerase II and enhanced repression of the basal transcription by PQBP-1. In this study, we have examined the effects of overexpression of PQBP-1 to the primary-cultured cerebellar neurons. Our results indicate that overexpression of PQBP-1 inhibits the basal transcription in cerebellar neurons and increases their vulnerability to low potassium conditions.

Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na+)-channel alpha 1 subunit gene, SCN1A.

Evidence that febrile seizures have a strong genetic predisposition has been well documented. In families of probands with multiple febrile convulsions, an autosomal dominant inheritance with reduced penetrance is suspected. Four candidate loci for febrile seizures have been suggested to date; FEB1 on 8q13-q21, FEB2 on 19p, FEB3 on 2q23-q24, and FEB4 on 5q14-15. A missense mutation was identified in the voltage-gated sodium (Na(+))-channel beta 1 subunit gene, SCN1B at chromosome 19p13.1 in generalized epilepsy with the febrile seizures plus type 1 (GEFS+1) family. Several missense mutations of the (Na(+))-channel alpha 1 subunit (Nav1.1) gene, SCN1A were also identified in GEFS+2 families at chromosome 2q23-q24.3. The aim of this report is precisely to describe the phenotypes of Japanese patients with novel SCN1A mutations and to reevaluate the entity of GEFS+. Four family members over three generations and one isolated (phenotypically sporadic) case with SCN1A mutations were clinically investigated. The common seizure type in these patients was febrile and afebrile generalized tonic-clonic seizures (FS+). In addition to FS+, partial epilepsy phenotypes were suspected in all affected family members and electroencephalographically confirmed in three patients of two families. GEFS+ is genetically and clinically heterogeneous, and associated with generalized epilepsy and partial epilepsy as well. The spectrum of GEFS+ should be expanded to include partial epilepsies and better to be termed autosomal dominant epilepsy with febrile seizures plus (ADEFS+).

Reduction in serotonin synthesis following acute and chronic treatments with paroxetine, a selective serotonin reuptake inhibitor, in rat brain: an autoradiographic study with alpha-[14C]methyl-L-tryptophan(2).

Serotonin (5-HT) synthesis rates were calculated on the basis of the assumption that trapping of alpha-[14C]methyl-L-tryptophan (alpha-[14C]MTrp) is directly related to brain 5-HT synthesis. In the first series of experiments, an acute intraperitoneal injection of paroxetine (10 mg/kg) produced a significant reduction in 5-HT synthesis in brain structures containing serotonergic cell bodies (the dorsal, median, and pallidum raphe nuclei), as well as in most projection areas: the ventral tegmental area, median forebrain bundle, hippocampus CA3 region, and nigrostriatal structures (substantia nigra, lateral and medial caudate nuclei). The reductions in the projection areas were greater (between 25 and 53%) than in those areas containing serotonergic cell bodies (between 18 and 23%). In the cerebral cortex, 5-HT synthesis rates were not modified by acute paroxetine treatment. In a second series of experiments, rats were treated with paroxetine (10 mg/kg/day, s.c., delivered by osmotic minipumps) for 14 days. There was a marked decrease (39-69%) in 5-HT synthesis in every structure examined. In conclusion, the present data suggest that the effects of paroxetine on 5-HT synthesis in the cerebral cortex are different from its effects in the cell body area of the brainstem.

Effects of acetazolamide on cerebral blood flow, blood volume, and oxygen metabolism: a positron emission tomography study with healthy volunteers.

To evaluate changes in cerebral hemodynamics and metabolism induced by acetazolamide in healthy subjects, positron emission tomography studies for measurement of cerebral perfusion and oxygen consumption were performed. Sixteen healthy volunteers underwent positron emission tomography studies with 15O-gas and water before and after intravenous administration of acetazolamide. Dynamic positron emission tomography data were acquired after bolus injection of H2[15O] and bolus inhalation of 15O2. Cerebral blood flow, metabolic rate of oxygen, and arterial-to-capillary blood volume images were calculated using the three-weighted integral method. The images of cerebral blood volume were calculated using the bolus inhalation technique of C[15O]. The scans for cerebral blood flow and volume and metabolic rate of oxygen after acetazolamide challenge were performed at 10, 20, and 30 minutes after drug injection. The parametric images obtained under the two conditions at baseline and after acetazolamide administration were compared. The global and regional values for cerebral blood flow and volume and arterial-to-capillary blood volume increased significantly after acetazolamide administration compared with the baseline condition, whereas no difference in metabolic rate of oxygen was observed. Acetazolamide-induced increases in both blood flow and volume in the normal brain occurred as a vasodilatory reaction of functioning vessels. The increase in arterial-to-capillary blood volume made the major contribution to the cerebral blood volume increase, indicating that the raise in cerebral blood flow during the acetazolamide challenge is closely related to arterial-to-capillary vasomotor responsiveness.

Localizing value of alpha-methyl-L-tryptophan PET in intractable epilepsy of neocortical origin.

BACKGROUND: [(11)C] alpha-methyl-L-tryptophan (alpha-MTrp) has been developed as a tracer for the study of the synthesis of serotonin in the brain with PET. However, it has been shown that in pathologic conditions the tracer may reflect the activation of kynurenine metabolism. Increased levels of serotonin and quinolinic acid have been described in resected epileptogenic cortex, raising the possibility that alpha-MTrp can localize seizure foci in patients with intractable partial epilepsy. The authors assessed the uptake of alpha-MTrp in 18 patients (11 men, mean +/- SD age 27.1 +/- 10.1 years, range 13 to 54) with intractable partial epilepsy to correlate the PET findings with the epileptogenic area defined by electroclinical and neuroimaging data. METHOD: Seven patients with cortical dysplasia (CD) and 11 with partial epilepsy in which conventional MRI and fluorine-18-deoxyglucose ((18)FDG)-PET studies failed to detect any abnormality were studied. All underwent scalp EEG monitoring during the PET scan to exclude ictal events and estimate the interictal epileptic activity. RESULTS: In seven patients (39%; CD four and cryptogenic partial epilepsy three), PET showed focal increased uptake of alpha-MTrp corresponding to the epileptogenic area. alpha-MTrp uptake in the epileptic focus correlated with the frequency of interictal spikes (r = 0.7, p < 0.05). CONCLUSIONS: alpha-MTrp-PET may be of value in the localization of the epileptogenic area not only in patients with visible dysplastic lesions, but also in those with cryptogenic partial epilepsy.

PQBP-1 (Np/PQ): a polyglutamine tract-binding and nuclear inclusion-forming protein.

Polyglutamine(Q) tract binding protein-1 (PQBP-1) was isolated on the basis of its interaction with polyglutamine tracts and localizes predominantly to the nucleus where it suppresses transcriptional activation by a neuron-specific transcription factor, Brn-2. Its C-terminal domain is highly conserved and binds to a component of the spliceosome. PQBP-1 possesses unique repetitive sequences that may fold as polar zippers. Interestingly, PQBP-1 also forms nuclear inclusion bodies, which are similar to those nucleated by the protein products of polyglutamine disease genes. Furthermore, because PQBP-1 is highly conserved in simple animal metazoans and plants (Caenorhabditis elegans and Arabidopsis), it may perform a basic function in cells. By the same token, disruption of the basic function could be critical to the disease process. Collectively, PQBP-1 might be a candidate molecule involved in the pathology of polyglutamine diseases. In this review, we discuss the structure and function of the PQBP-1 protein, the relevance of its aggregation and possible roles in normal and disease processes.

Quantitative comparison of the bolus and steady-state methods for measurement of cerebral perfusion and oxygen metabolism: positron emission tomography study using 15O-gas and water.

To evaluate a new simplified bolus method for measurement of cerebral perfusion and metabolism, the parametric images with that method were compared with those obtained from the conventional steady-state method with 15O-gas. The new method also provided images of arterial blood volume (V0), which is a different parameter from cerebral blood volume (CBV) obtained using a C15O technique. Seven healthy volunteers and 10 patients with occlusive cerebrovascular diseases underwent positron emission tomography (PET) scans with both methods. Three-weighted integration was applied to calculate regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2) in the bolus method. Global and regional CBF and CMRO2 in volunteers were compared between the two methods and used as control data. Regional values in patients also were evaluated to observe differences between the bilateral hemispheres. Both rCBF and rCMRO2 were linearly well correlated between the two methods, although global difference in CMRO2 was significant. The difference in each parametric image except for V0 was significant between the bilateral hemispheres in patients. The bolus method can simplify oxygen metabolism studies and yield parametric images comparable with those with the steady-state method, and can allow for evaluation of V0 simultaneously. Increase in CBV without a change in V0 suggested the increase might mainly be caused by venous dilatation in the ischemic regions.

Effect of vascular radioactivity on regional values of cerebral blood flow: evaluation of methods for H(2)(15)O PET to distinguish cerebral perfusion from blood volume.

UNLABELLED: To evaluate the appropriate model for calculating regional cerebral blood flow (rCBF) with PET and H(2)(15)O, the values obtained from 1- and 2-compartment analyses were compared. METHODS: Dynamic PET scans were performed on 12 healthy volunteers after injection of H(2)(15)O in 2 conditions of baseline and visual stimulation. Calculation of rCBF was performed using the 2-weighted integral (WI) and autoradiographic methods for the 1-compartment analysis, and the 3-WI method was followed for the 2-compartment analysis. Arterial blood radioactivity was counted continuously and corrected for delay and dispersion. The rCBF images were transformed into the Talairach space and analyzed by statistical parametric mapping to identify regional differences in the 2 methods. The values obtained from regions of interest also were compared. RESULTS: Although the difference in global CBF between the 2 models was not significant, rCBF values in the large arteries and neighbor areas were significantly greater in the 2-WI method than in the 3-WI method. However, regional differences in the activation studies were not affected when the 2 methods were compared. The images of cerebral arterial blood volume (V(0)) obtained by the 3-WI method showed a significant increase in V(0) in the visual cortex during visual stimulation. CONCLUSION: These results suggest that the rCBF values in the 1-compartment analysis were affected by radioactivity in the vessels. The 3-WI method could provide rCBF values that are less influenced by vascular radioactivity and also show differences in V(0) in PET activation studies.