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.

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.

Bcl-2 inhibits retinoic acid-induced apoptosis during the neural differentiation of embryonal stem cells.

We report here that all trans-retinoic acid (RA), a classical morphogen, induces apoptosis during the neural differentiation of the embryonic stem cell line P19. The apoptotic cells showed, in addition to DNA cleavage, typical morphological changes including chromatin condensation, nuclear fragmentation, and cytoplasmic vacuolation. These apoptotic changes became obvious by 12 h after the addition of RA. The endogenous expression of bcl-2 in surviving cells was down-regulated during this process, and the compelled expression of bcl-2 by retroviral vectors reduced the number of apoptotic cells. Apoptosis was partially inhibited by adding antisense oligonucleotides against RA receptors (RARs) simultaneously or by transfecting a plasmid vector flanked with a RA-responsive element. Antisense oligonucleotides against retinoid X receptors (RXRs), the receptors for 9 cis-RA, did not inhibit apoptosis induced by all trans-RA. Cycloheximide and actinomycin D, inhibitors of protein and RNA syntheses, respectively, suppressed apoptosis. No changes were seen in the expression of tumor necrosis factors, their receptors, Fas, FasL, p53, or c-myc, molecules which have been suggested to participate in the apoptotic process. Addition of neurotrophins to the culture medium did not affect apoptosis. These findings suggest that the signals themselves, promote expression of molecules essential for apoptosis. Furthermore, we observed that RA induced apoptosis of cerebral neurons from murine embryos in primary culture, which suggests that RA might participate in cell death which occurs during neural development.

Presenilin 1 suppresses the function of c-Jun homodimers via interaction with QM/Jif-1.

Presenilin 1 (PS1) is the causative gene for an autosomal dominant familial Alzheimer's disease (AD) mapped to chromosome 14. Here we show that QM/Jun-interacting factor (Jif)-1, a negative regulator of c-Jun, is a candidate to mediate the function of PS1 in the cell. We screened for proteins that bind to PS1 from a human embryonic brain cDNA library using the two-hybrid method and isolated one clone encoding the QM/Jif-1 gene. The binding of QM/Jif-1 to full-length PS1 was confirmed in vitro by pull-down assay, and in vivo by immunoprecipitation assays with human samples, including AD brains. Immunoelectronmicroscopic analysis showed that QM/Jif-1 and PS1 are colocalized at the endoplasmic reticulum, and the nuclear matrix in human brain neurons. Chloramphenicol acetyltransferase assays in F9 cells showed that PS1 suppresses transactivation by c-Jun/c-Jun but not by c-Jun/c-Fos heterodimers, consistent with the reported function of QM/Jif-1. By monitoring fluorescent recombinant protein and by gel mobility shift assays, PS1 was shown to accelerate the translocation of QM from the cytoplasm to the nucleus and to thereby suppress the binding of c-Jun homodimer to 12-O-tetradecanoylphorbol-13- acetate (TPA)-responsive element (TRE). PS1 suppressed c-jun-associated apoptosis by retinoic acid in F9 embryonic carcinoma cells, whereas this suppression of apoptosis is attenuated by mutation in PS1. Collectively, the novel function of PS1 via QM/Jif-1 influences c-jun-mediated transcription and apoptosis.

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.

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.

Gene regulation of trkB and trkC in the chick retina by light/darkness exposure.

The trk gene family members; the neurotrophic receptors for neurotrophins, are implicated in the survival and the differentiation of neurons. The roles of these protooncogenes have been argued in the pathological conditions and in the specific developmental stage when the programmed cell death occurs to neurons. Here we studied a physiological role of the trk family members in the retina through observations of their gene regulation by light/darkness exposure. Northern blot analysis and immunohistochemistry demonstrate that trkB and trkC are up-regulated by light exposure and down-regulated by darkness in the rod/cone layer, the outer nuclear layer, and the ganglion cell layer. This physiological regulation suggests that these trk family members play a protective role from the damaging effect of light exposure in the retinal neurons.

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.

Molecular screening of uncoupling protein 2 gene in patients with noninsulin-dependent diabetes mellitus or obesity.

Uncoupling protein 2 (UCP2), a member of the family of mitochondrial carrier proteins, has been implicated in the control of whole-body energy balance. The coding region of the human UCP2 gene has now been shown to comprise six exons, and the sequences of the exon-intron boundaries were determined. With the use of this sequence information, 25 Japanese patients with obesity and noninsulin-dependent diabetes mellitus (NIDDM) and 25 subjects with simple obesity were screened for mutations in the entire coding region of UCP2 by PCR and single-strand conformation polymorphism analysis. Two nucleotide polymorphisms resulting in Ala55 --> Val and Ala232 --> Thr substitutions were detected. With the use of PCR and restriction fragment length polymorphism analysis, the allele frequencies for each of these polymorphisms were determined in 210 Japanese patients with NIDDM, 42 obese individuals, and 218 normal control subjects. The frequency of the Val55 allele did not differ significantly among the NIDDM group (46.0%), the obesity group (48.8%), and the normal control group (48.4%). The Thr232 allele was detected in only three subjects, who were heterozygotes and in the NIDDM group (allele frequency, 0.7%). However, expression in yeast of the human wild-type UCP2 protein and UCP2 containing Thr232 revealed no difference in functional activity. These results indicate that the Ala55 --> Val and Ala232 --> Thr variants of UCP2 do not play an important role in the pathogenesis of NIDDM or obesity in the Japanese population.

Selective cerebral hematocrit decrease in the centrum semiovale after carotid artery occlusion: a PET study.

The centrum semiovale may be susceptible to hypoperfusion as a result of carotid artery occlusion. Recent studies suggest that the cerebral hematocrit decreases with diminished cerebral perfusion pressure. To investigate whether the effect of carotid artery occlusion on the hematocrit in the centrum semiovale is different from that in the cerebral cortex, seven patients with unilateral carotid artery occlusion were studied with positron emission tomography. The distributions of the red blood cell and plasma volumes were assessed using carbon monoxide labeled with oxygen 15 and human serum albumin-dithiosemicarbazone tracers labeled with copper 62, respectively. The CBF and CMRO2 were also measured with the (15)O steady-state technique. The calculated values for the hematocrit in the centrum semiovale ipsilateral to the arterial occlusion were significantly decreased compared with those in any of the other regions examined (the overlying cortical region and the contralateral cortex and centrum semiovale). This decrease in hematocrit, which resulted from a more pronounced increase in plasma volume than in red blood cell volume, was associated with a decrease in CBF and an increase in the oxygen extraction fraction. Hemodynamic disturbance caused by carotid artery occlusion may induce selective decrease of hematocrit limited to the centrum semiovale.

Validation of a less-invasive method for measurement of serotonin synthesis rate with alpha-[11C]methyl-tryptophan.

We tested in normal human subjects a less invasive method to obtain plasma input function required in the calculation of the brain serotonin synthesis rate measured with positron emission tomography (PET) and alpha-[11C]methyl-tryptophan (alpha-MTrp). The synthesis rates derived with the arterial input function were compared to those derived from venous plasma and venous sinus time-radioactivity curves obtained from dynamic PET images. Dynamic PET images were obtained for the lengths up to 90 minutes after an injection of alpha-MTrp (400 to 800 MBq). Input functions were generated from both artery and vein in three subjects, and from artery only in two subjects. Net unidirectional uptake constants of alpha-MTrp (K*; mL/g/min) were calculated in several brain regions graphically using data between 20 and 60 minutes after injection with different input functions. In the five subjects with arterial sampling, we tested two methods for correcting the input functions from the venous samples: (1) normalization to the mean exposure time at 20 minutes from arterial curve; and (2) the use of the venous sinus curve for the first 20 minutes. Venous curves coincided with the arterial ones after about 20 minutes. When the venous curves were used, there was an underestimation of the area under the curves up to 20 minutes, resulting in a 5% to 30% overestimation of K* values. Combined use of the sinus curve up to 20 minutes and venous curve from 20 to 60 minutes as an input function resulted in the K* (mL/g/min) values larger by 7.1 +/- 3.8% than the K* values estimated with the arterial input function. Normalization of the venous curve to the exposure time at 20 minutes obtained from the arterial plasma curve resulted in a bias in the K* of about -0.34 +/- 3.32%. The bias from the K* values was propagated to the serotonin synthesis rates. The use of a combination of the venous blood samples and venous sinus as the input function resulted in an acceptable bias in the serotonin synthesis rates from the tissue time-radioactivity curves generated by PET.

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.

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.

Brain Regional alpha-[11C]methyl-L-tryptophan trapping in impulsive subjects with borderline personality disorder.

OBJECTIVE: Neurotransmission of serotonin (or 5-hydroxytryptamine [5-HT]) is thought to be disturbed in patients exhibiting impulsive behaviors. However, until recently it has not been possible to test this hypothesis in the brains of living humans. METHOD: Unidirectional trapping of the 5-HT precursor analog alpha-[(11)C]methyl-L-tryptophan (alpha-[(11)C]MTrp) has been proposed as an index of 5-HT synthesis capacity. The authors measured brain regional alpha-[(11)C]MTrp trapping with positron emission tomography in medication-free subjects with borderline personality disorder (N=13) and a healthy comparison group (N=11). Impulsivity was assessed by using a laboratory measure of behavioral disinhibition, go/no-go commission errors. RESULTS: Compared to healthy men, the men with borderline personality disorder had significantly lower alpha-[(11)C]MTrp trapping in corticostriatal sites, including the medial frontal gyrus, anterior cingulate gyrus, superior temporal gyrus, and corpus striatum. In the women with borderline personality disorder, significantly lower alpha-[(11)C]MTrp trapping was seen in fewer regions, but in both men and women, negative correlations with impulsivity scores were identified in the medial frontal gyrus, anterior cingulate gyrus, temporal gyrus, and striatum. CONCLUSIONS: Low 5-HT synthesis capacity in corticostriatal pathways may contribute to the development of impulsive behaviors in persons with borderline personality disorder.

Molecular cloning and expression of a novel truncated form of chicken trkC.

The trk family of tyrosine protein kinase genes serves crucial roles for the development of the nervous system and the survival of neurons. The members of this gene family, trk, trkB and trkC, bind a distinct neurotrophin of the nerve growth factor (NGF) gene family, and trigger the intracellular signals which elicit trophic and differentiating effects on neurons. Adding to these neurotrophic receptor kinases, the truncated forms without the tyrosine kinase domain have been cloned and characterized. It has been thought that the existence of truncated forms is limited to trkB; however, very recently the truncated trkC has been cloned in rat [(1993) Neuron 10, 963-974; (1993) Neuron 10, 975-990]. We independently approached and molecularly cloned a truncated form which belongs to the chicken trkC. The truncated trkC possesses the binding and the transmembrane domains but not the tyrosine kinase domain. Northern blot analysis shows that the truncated form is preferentially expressed in the adult central nervous system. The truncated form is scarcely expressed during the embryonic stages. The conservation of the truncated trkC beyond species suggests they have specific functions.

Dopaminergic stimulation up-regulates the in vivo expression of brain-derived neurotrophic factor (BDNF) in the striatum.

We investigated the effect of dopamine on the in vivo expression of brain-derived neurotrophic factor (BDNF) in the striatum of mouse. BDNF mRNA expression in the striatum, which was quantified with the reverse transcriptase polymerase chain reaction, was up-regulated from 2 h after oral administration of levodopa, a precursor of dopamine. The increase was sustained for 16 h. Co-administration of haloperidol partially inhibited dopamine-induced BDNF enhancement. These data suggest that dopaminergic stimulation directly promotes the expression of BDNF in the striatum in vivo.

Long-term changes of hemodynamics and metabolism after carotid artery occlusion.

OBJECTIVE: To investigate whether in selected patients with internal carotid artery (ICA) occlusion and initially normal oxygen extraction fraction (OEF) measured with PET, subsequent changes of cerebral hemodynamics and metabolism occur during long-term follow-up and, if so, whether the changes are associated with atrophy of the corpus callosum or subsequent ischemic strokes. BACKGROUND: The course of the changes in cerebral hemodynamics and metabolism after ICA occlusion remain unclear. After ICA occlusion, an increase in OEF may increase the risk of cerebral ischemia, and an increase in cortical ischemia would cause progression of callosal atrophy. METHODS: The authors used PET and MRI to examine twice seven medically treated patients with unilateral ICA occlusion and initially normal OEF at intervals ranging from 24 to 64 (mean +/- SD, 42 +/- 17) months. No intervening ischemic attacks occurred between the two examinations. RESULTS: In the hemisphere with ICA occlusion, OEF increased and blood flow decreased during follow-up. At the follow-up evaluation, abnormally increased OEF values were found in three patients, in whom ipsilateral ischemic strokes occurred during subsequent follow-up (18 +/- 6 months). A decrease in oxygen metabolism also occurred and was significantly correlated with the decrease of callosal size. CONCLUSIONS: These preliminary findings in a small, selected patient sample suggest that in patients with ICA occlusion and initially normal OEF, deteriorations of cerebral hemodynamics and metabolism during long-term follow-up may be associated with callosal atrophy or subsequent ischemic strokes.

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.

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.

Delayed data acquisition for optimal PET activation studies with oxygen-15-water in cerebral arteriovenous malformation.

UNLABELLED: In the clinical application of activation PET studies with 15O-water, optimal PET images are required when the high activity of a nearby lesion might affect the activated area. METHODS: To determine the optimal time for data acquisition of PET images, we performed serial dynamic PET measurements in five patients with cerebral arteriovenous malformation (AVM). All AVMs were closest to the motor cortices, and the activation task was opponent finger movement contralateral to the AVM. Activation PET and MR images were coregisterated for localization of activated foci. RESULTS: Time-activity curves of the nidus and normal cortex from the dynamic PET data demonstrated a discrepancy in peak time and significant radioactivity increase in the nidus during the early phase. Elimination of the initial PET data provided better contrast in activated foci without affecting the calculated cerebral blood flow of other areas. CONCLUSION: Delayed data acquisition can avoid interference of the AVM nidus with the activated area.