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Objectives: A previous study reported that a differential diagnosis between glioblastoma progression and radiation necrosis by 4-borono-2-[ 18 F]-fluoro-phenylalanine ([ 18 F]FBPA) PET can be made based on lesion-to-normal ratio of [ 18 F]FBPA accumulation. Two-dimensional data acquisition mode PET alone system, with in-plane resolution of 7.9 mm and axial resolution of 13.9 mm, was used. In the current study, we aimed to confirm the differential diagnostic capability of [ 18 F]FBPA PET/CT with higher PET spatial resolution by three-dimensional visual inspection and by measuring mean standardized uptake value (SUVmean), maximum SUV (SUVmax), metabolic tumor volume (MTV), and total lesion (TL) [ 18 F]FBPA uptake., Methods: Twelve patients of glioma (9), malignant meningioma (1), hemangiopericytoma (1), and metastatic brain tumor (1) were enrolled. All had preceding radiotherapy. High-resolution three-dimensional data acquisition mode PET/CT with in-plane resolution of 4.07 mm and axial resolution of 5.41 mm was employed for imaging. Images were three-dimensionally analyzed using the PMOD software. SUVmean and SUVmax of lesion and normal brain were measured. Lesion MTV and TL FBPA uptake were calculated. The diagnostic accuracy of [ 18 F]FBPA PET/CT in detecting recurrence (n = 6) or necrosis (n = 6) was verified by clinical follow-up., Results: All parameters showed significantly higher values for tumor recurrence than for necrosis. SUVmean in recurrence was 2.95 ± 0.84 vs 1.18 ± 0.24 in necrosis (P = 0.014); SUVmax in recurrence was 4.63 ± 1.23 vs 1.93 ± 0.44 in necrosis (P = 0.014); MTV in recurrence was 44.92 ± 28.93 mL vs 10.66 ± 8.46 mL in necrosis (P = 0.032); and mean TL FBPA uptake in recurrence was 121.01 ± 50.48 g vs 12.36 ± 9.70 g in necrosis (P = 0.0029)., Conclusion: In this preliminary feasibility study, we confirmed the possibility of differentiating tumor recurrence from radiation necrosis in patients with irradiated brain tumors by [ 18 F]FBPA PET/CT using indices of SUVmean, SUVmax, MTV, and TL 18 FBPA uptake.

Objective: Resting-state functional MRI (rs-fMRI) has revealed the existence of a default-mode network (DMN) based on spontaneous oscillations of the blood oxygenation level-dependent (BOLD) signal. The BOLD signal reflects the deoxyhemoglobin concentration, which depends on the relationship between the regional cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO 2 ). However, these two factors cannot be separated in BOLD rs-fMRI. In this study, we attempted to estimate the functional correlations in the DMN by means of quantitative 15 O-labeled gases and water PET, and to compare the contribution of the CBF and CMRO 2 to the DMN., Methods: Nine healthy volunteers (5 men and 4 women; mean age, 47.0 ± 1.2 years) were studied by means of 15 O-O 2 , 15 O-CO gases and 15 O-water PET. Quantitative CBF and CMRO 2 images were generated by an autoradiographic method and transformed into MNI standardized brain template. Regions of interest were placed on normalized PET images according to the previous rs-fMRI study. For the functional correlation analysis, the intersubject Pearson's correlation coefficients (r) were calculated for all pairs in the brain regions and correlation matrices were obtained for CBF and CMRO 2 , respectively. We defined r > 0.7 as a significant positive correlation and compared the correlation matrices of CBF and CMRO 2 ., Results: Significant positive correlations (r > 0.7) were observed in 24 pairs of brain regions for the CBF and 22 pairs of brain regions for the CMRO 2 . Among them, 12 overlapping networks were observed between CBF and CMRO 2 . Correlation analysis of CBF led to the detection of more brain networks as compared to that of CMRO 2 , indicating that the CBF can capture the state of the spontaneous activity with a higher sensitivity., Conclusions: We estimated the functional correlations in the DMN by means of quantitative PET using 15 O-labeled gases and water. The correlation matrix derived from the CBF revealed a larger number of brain networks as compared to that derived from the CMRO 2 , indicating that contribution to the functional correlation in the DMN is higher in the blood flow more than the oxygen consumption.

Background: Although apathy is associated with damage to the frontal and temporal lobes in Alzheimer's disease (AD), the crucial regions for apathy in patients with amnestic mild cognitive impairment (aMCI) are unknown., Objective: To identify brain regions associated with apathy in aMCI patients., Methods: The subjects of this study were 98 aMCI patients who were entered in our dementia registry between March 1, 2009 and April 30, 2015 and who satisfied our criteria for aMCI. The association between the apathy score of the Neuropsychiatric Inventory and regional gray matter volume was analyzed using voxel-based morphometry. The association between apathy score and regional cerebral blood flow (rCBF) measured with single photon emission computed tomography (SPECT) was analyzed using Statistical Parametric Mapping., Results: The aMCI patients were classified into aMCI with and without "SPECT images suggestive of AD" (aMCI-AD+ and aMCI-AD-, respectively) based on the Z-score summation analysis method. In aMCI-AD+ (n = 31), apathy was significantly and negatively correlated with gray matter volume in the right caudate nucleus and with rCBF in five regions (left posterior-medial frontal lobe, right superior frontal lobe, bilateral culmen-fusiform gyri, and left occipital lobe). In aMCI-AD-(n = 67), apathy was significantly and negatively correlated with gray matter volumes in five regions but it was not correlated with rCBF in any regions., Conclusion: In patients with a high probability of being in the aMCI stage of AD, apathy was associated with atrophy of the right caudate nucleus and hypoperfusion in the frontal, temporal and occipital lobes.

Background: Integrated SPECT/CT enables non-uniform attenuation correction (AC) using built-in CT instead of the conventional uniform AC. The effect of CT-based AC on voxel-based statistical analyses of brain SPECT findings has not yet been clarified. Here, we assessed differences in the detectability of regional cerebral blood flow (CBF) reduction using SPECT voxel-based statistical analyses based on the two types of AC methods., Subjects and Methods: N-isopropyl-p-[123I]iodoamphetamine (IMP) CBF SPECT images were acquired for all the subjects and were reconstructed using 3D-OSEM with two different AC methods: Chang's method (Chang's AC) and the CT-based AC method. A normal database was constructed for the analysis using SPECT findings obtained for 25 healthy normal volunteers. Voxel-based Z-statistics were also calculated for SPECT findings obtained for 15 patients with chronic cerebral infarctions and 10 normal subjects. We assumed that an analysis with a higher specificity would likely produce a lower mean absolute Z-score for normal brain tissue, and a more sensitive voxel-based statistical analysis would likely produce a higher absolute Z-score for in old infarct lesions, where the CBF was severely decreased., Results: The inter-subject variation in the voxel values in the normal database was lower using CT-based AC, compared with Chang's AC, for most of the brain regions. The absolute Z-score indicating a SPECT count reduction in infarct lesions was also significantly higher in the images reconstructed using CT-based AC, compared with Chang's AC (P = 0.003). The mean absolute value of the Z-score in the 10 intact brains was significantly lower in the images reconstructed using CT-based AC than in those reconstructed using Chang's AC (P = 0.005)., Conclusions: Non-uniform CT-based AC by integrated SPECT/CT significantly improved sensitivity and the specificity of the voxel-based statistical analyses for regional SPECT count reductions, compared with conventional uniform Chang's AC.

Unlabelled: Genetic or environmental influences on cerebral glucose metabolism are unknown. We attempted to reveal these influences in elderly twins by means of (18)F-FDG PET., Methods: (18)F-FDG uptake was studied in 40 monozygotic and 18 dizygotic volunteer twin pairs aged 30 y or over. We also created 18 control pairs by pairing age- and sex-matched genetically unrelated subjects from dizygotic and monozygotic pairs. SUV images of the brain were reconstructed and analyzed by voxel-based statistical analysis with automated region-of-interest setting. The (18)F-FDG uptake in each cerebral lobe was semiquantified by taking a ratio of SUVmean in each region of interest to whole-brain SUVaverage. We calculated an intraclass correlation coefficient of SUV ratio in each region of interest for monozygotic and dizygotic pairs. By comparing differences in coefficients between monozygotic and dizygotic pairs, genetic and environmental contributions were estimated., Results: The intraclass correlation coefficient in monozygotic pairs was significantly higher than that in dizygotic pairs in the parietal lobes bilaterally (P < 0.001) and in the left temporal lobe (P < 0.05) but was not significantly different in other lobes., Conclusion: The present study indicated that in the right and left parietal lobes and left temporal lobe, cerebral glucose metabolism is influenced more by genetics than by environment, whereas in other brain regions the influence of environment is dominant., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Background: Activation of glial cells is a cardinal feature in multiple sclerosis (MS) pathology, and acetate has been reported to be selectively uptaken by astrocytes in the CNS. The aim of this study was to investigate the efficacy of PET with (11)C-acetate for MS diagnosis., Materials and Methods: Six patients with relapsing-remitting MS and 6 healthy volunteers (HV) were enrolled. The (11)C-acetate brain uptake on PET was measured in patients with MS and HV. Volume-of-interest analysis of cerebral gray and white matter based on the segmentation technique for co-registered MRI and voxel-based statistical parametric analysis were performed. Correlation between 11C-acetate uptake and the lesion number in T1- and T2- weighted MR images were also assessed., Results: The standardized uptake value (SUV) of 11C-acetate was increased in both white and gray matter in MS patients compared to HV. Voxel-based statistical analysis revealed a significantly increased SUV relative to that in the bilateral thalami (SUVt) in a broad area of white matter, particularly in the subcortical white matter of MS patients. The numbers of T2 lesions and T1 black holes were significantly correlated with SUV of (11)C-acetate in white and gray matter., Conclusions: The 11C-acetate uptake significantly increased in MS patients and correlated to the number of MRI lesions. These preliminary data suggest that (11)C-acetate PET can be a useful clinical examination for MS patients.

Purpose: A recently developed technique which reconstructs quantitative images from original projection data acquired using existing single-photon emission computed tomography (SPECT) devices enabled quantitative assessment of cerebral blood flow (CBF) at rest and after acetazolamide challenge. This study was intended to generate a normal database and to investigate its inter-institutional consistency., Methods: The three institutions carried out a series of SPECT scanning on 32 healthy volunteers, following a recently proposed method that involved dual administration of (123)I-iodoamphetamine during a single SPECT scan. Intra-institute and inter-institutional variations of regional CBF values were evaluated both at rest and after acetazolamide challenge. Functional images were pooled for both rest and acetazolamide CBF, and inter-institutional difference was evaluated among these images using two independent software programs., Results: Quantitative assessment of CBF images at rest and after acetazolamide was successfully achieved with the given protocol in all institutions. Intra-institutional variation of CBF values at rest and after acetazolamide was consistent with previously reported values. Quantitative CBF values showed no significant difference among institutions in all regions, except for a posterior cerebral artery region after acetazolamide challenge in one institution which employed SPECT device with lowest spatial resolution. Pooled CBF images at rest and after acetazolamide generated using two software programs showed no institutional differences after equalization of the spatial resolution., Conclusions: SPECT can provide reproducible images from projection data acquired using different SPECT devices. A common database acquired at different institutions may be shared among institutions, if images are reconstructed using a quantitative reconstruction program, and acquired by following a standardized protocol.

Local cerebral perfusion pressure (CPP) is a primary factor controlling cerebral circulation and previous studies have indicated that the ratio of cerebral blood flow (CBF) to cerebral blood volume (CBV) can be used as an index of the local CPP. In this study, we investigated whether the CBF/CBV ratio differs among different brain structures under physiological conditions, by means of (15)O positron emission tomography. Nine healthy volunteers (5 men and 4 women; mean age, 47.0 ± 1.2 years) were studied by H2 (15)O bolus injection for CBF measurement and by C(15)O inhalation for CBV measurement. The CBF/CBV ratio maps were created by dividing the CBF images by the CBV images after anatomical normalization. Regions of interest were placed on the CBF/CBV maps and comparing the regions. The mean CBF/CBV ratio was highest in the cerebellum (19.3 ± 5.2/min), followed by the putamen (18.2 ± 3.9), pons (16.4 ± 4.6), thalamus (14.5 ± 3.3), cerebral cortices (13.2 ± 2.4), and centrum semiovale (11.5 ± 2.1). The cerebellum and putamen showed significantly higher CBF/CBV ratios than the cerebral cortices and centrum semiovale. We created maps of the CBF/CBV ratio in normal volunteers and demonstrated higher CBF/CBV ratios in the cerebellum and putamen than in the cerebral cortices and deep cerebral white matter. The CBF/CBV may reflect the local CPP and should be studied in hemodynamically compromised patients and in patients with risk factors for small-artery diseases of the brain.

Background and Purpose: It has been suggested, on the basis of a previous pilot study conducted in a small number of patients, that MR imaging-based PVE correction in I-123 iomazenil brain SPECT improves the detectability of cortical epileptogenic foci. In the present study, we performed an investigation by using a larger sample size to establish the effectiveness of the PVE correction and to conduct a detailed evaluation based on the histologic classification of lesions., Materials and Methods: Seventy-five patients (male/female, 37/38; age, 28 ± 12 years) with intractable epilepsy who had undergone surgical treatment were enrolled in this study. I-123 iomazenil SPECT and MR imaging examinations were performed before the operation in all patients. I-123 iomazenil SPECT images with and without MR imaging-based PVE correction were assessed visually and by semiquantitative analysis based on the AI(%) of the SPECT count in the resected lesions., Results: The sensitivity, specificity, and accuracy of foci detection by visual assessment were significantly higher after PVE correction compared with the values obtained before the correction. The results of the semiquantitative analysis revealed that the asymmetry of the SPECT counts was significantly increased after the PVE correction in the surgically resected lesions in cases of mesial temporal sclerosis, tumor, and malformations of cortical development., Conclusions: The effectiveness of MR imaging-based PVE correction in I-123 iomazenil brain SPECT in improving the detection of cortical epileptogenic foci with abnormal histologic findings was established by our investigation conducted on a large sample size.

Background and Purpose: CBR imaging is highly susceptible to a PVE produced by morphologic changes in the brain related to aging and brain laterality. We assessed the influence of PVE produced by regional age-related changes in gray matter volume on I-123 iomazenil SPECT and elucidated the age-related changes in human CBR binding by using PVE-corrected SPECT images., Materials and Methods: Nineteen right-handed healthy volunteers (range, 25-82 years; mean, 55 ± 21 years) underwent MR imaging and quantitative I-123 iomazenil SPECT imaging. The influence of age-related changes in rGMC on SPECT images before PVE correction was assessed. PVE correction of the SPECT images was performed by using an MR imaging-based method. Voxel-based linear regression analyses of the PVE-corrected SPECT images were performed by using SPM5., Results: The age-related reductions in rGMC and BP without PVE correction revealed a significant direct proportional correlation. Voxel-based statistical analysis with PVE correction showed no significant age-related changes in BP., Conclusions: PVE correction was indispensable for the analysis of I-123 iomazenil SPECT images. PVE-corrected quantitative I-123 iomazenil SPECT images revealed no age-related changes in CBR binding in right-handed healthy humans.

Purpose: We developed a new type of scintillation detector ring for positron emission tomography (PET). In this device the scintillation detectors were connected with 2.6 m length optic fibers to transport scintillation light to a photomultiplier (PMT) located apart from the detector rings. The present study aimed to test the possibility of simultaneous imaging with PET and magnetic resonance imaging (MRI) by means of the present PET device in ex vivo rat brain., Materials and Methods: The scintillation detector ring of 4 cm diameter was located in a magnetic field of 0.15 T open MRI. Simultaneous measurements of PET and MRI were performed in ex vivo rat brain after injection of (18)F-fluorodeoxyglucose ((18)F-FDG) 37 MBq and (18)F-NaF 37 MBq. Simultaneous data acquisition was performed for 10 min for PET and 5 min for T1-weighted MRI., Results: Simultaneous imaging of PET and MRI was possible without noticeable image distortion in the PET and MRI scans. In the fusion images, high uptake of (18)F-FDG was identified in the Harderian glands and striatum. High uptake of (18)F-NaF was found in the skull base and vault., Conclusions: The present study indicated the possibility of simultaneous imaging of PET and MRI by means of optic fiber-based scintillation detectors.

Objective: A planar positron imaging system (PPIS) enables whole-body dynamic imaging of radiopharmaceuticals labeled with positron-emitting nuclides. We evaluated the difference in the brain and whole-body pharmacokinetics of (11)C-diphenylhydantoin ((11)C-DPH) between intravenous and duodenal administration in rats., Methods: Male Wistar rats (8 weeks old, mean body weight 250 g) were examined under anesthesia. A tracer amount of (11)C-DPH (2 microg or less; about 5 MBq) was injected into the tail vein (n = 3) or duodenum (n = 3). Immediately following the administration, PPIS scans were obtained for 20 min. Regions of interest (ROIs) were set on the brain, heart, liver, intestinal field, and urinary bladder, identified on the integrated images. The relative uptake value (RUV, %) was calculated as the regional count divided by the whole-body count multiplied by 100. Sequential changes in the RUV for each ROI were analyzed for the brain and other organs., Results: Following intravenous injection of (11)C-DPH, the RUV in the brain was 1.59 +/- 0.07%, 1.53 +/- 0.09%, 1.40 +/- 0.09%, and 1.38 +/- 0.08% at 5 min, 10 min, 15 min, and 20 min after the injection, respectively. After duodenal administration, the corresponding values were 0.54 +/- 0.16%, 1.01 +/- 0.12%, 1.43 +/- 0.24%, and 1.52 +/- 0.06%, respectively. The (11)C-DPH distribution was significantly lower at 5 min and 10 min following duodenal administration than after intravenous injection (P < 0.01). Radioactivity in the urinary bladder was identified by 20 min after both intravenous injection and duodenal administration., Conclusions: The present study demonstrated a difference in the brain distribution of (11)C-DPH between intravenous and duodenal administration in rats. Use of the PPIS is feasible for the evaluation of the pharmacokinetics in both the target organ and the whole body in small animals.

Unlabelled: (123)I-Iomazenil brain SPECT has been used for the detection of epileptogenic foci, especially when surgical intervention is considered. Although epileptogenic foci exhibit a decrease in (123)I-iomazenil accumulation, normal cerebral cortices often exhibit similar findings because of thin cortical ribbons, gray matter atrophy, or pathologic brain structures. In the present study, we created (123)I-iomazenil SPECT images corrected for gray matter volume using MRI and tested whether the detectability of the epileptogenic foci improved., Methods: Seven patients (1 male patient and 6 female patients; mean age +/- SD, 34 +/- 17 y) with intractable epilepsy were surgically treated by resecting the cerebral cortex after surface electroencephalography. Histopathologic examination of the resected specimens and a good outcome after surgery indicated that the resected lesions were epileptogenic foci. These patients underwent (123)I-iomazenil SPECT and 3-dimensional T1-weighted MRI examinations before their operations. Each SPECT image was coregistered to the corresponding MR image, and its partial-volume effect (PVE) was corrected on a voxel-by-voxel basis with a smoothed gray matter distribution image. Four nuclear medicine physicians visually evaluated the (123)I-iomazenil SPECT images with and without the PVE correction. The SPECT count ratio of the suspected focus to the contralateral cerebral cortex was evaluated as an asymmetry index (%) based on the volume of interest., Results: The sensitivity, specificity, and accuracy of focus detection by visual assessment were higher after PVE correction (88%, 99%, and 98%, respectively) than before correction (50%, 92%, and 87%, respectively). The mean asymmetry index for the surgically resected lesions was significantly higher on the PVE-corrected SPECT images (22%) than on the PVE-uncorrected ones (16%) (P = 0.006)., Conclusion: MRI-based PVE correction for (123)I-iomazenil brain SPECT improves the sensitivity and specificity of the detection of cortical epileptogenic foci in patients with intractable epilepsy.

Unlabelled: Quantitative PET with (15)O provides absolute values for cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF), which are used for assessment of brain pathophysiology. Absolute quantification relies on physically accurate measurement, which, thus far, has been achieved by 2-dimensional PET (2D PET), the current gold standard for measurement of CBF and oxygen metabolism. We investigated whether quantitative (15)O study with 3-dimensional PET (3D PET) shows the same degree of accuracy as 2D PET., Methods: 2D PET and 3D PET measurements were obtained on the same day on 8 healthy men (age, 21-24 y). 2D PET was performed using a PET scanner with bismuth germanate (BGO) detectors and a 150-mm axial field of view (FOV). For 3D PET, a 3D-only tomograph with gadolinium oxyorthosilicate (GSO) detectors and a 156-mm axial FOV was used. A hybrid scatter-correction method based on acquisition in the dual-energy window (hybrid dual-energy window [HDE] method) was applied in the 3D PET study. Each PET study included 3 sequential PET scans for C(15)O, (15)O(2), and H(2)(15)O (3-step method). The inhaled (or injected) dose for 3D PET was approximately one fourth of that for 2D PET., Results: In the 2D PET study, average gray matter values (mean +/- SD) of CBF, CBV, CMRO(2), and OEF were 53 +/- 12 (mL/100 mL/min), 3.6 +/- 0.3 (mL/100 mL), 3.5 +/- 0.5 (mL/100 mL/min), and 0.35 +/- 0.06, respectively. In the 3D PET study, scatter correction strongly affected the results. Without scatter correction, average values were 44 +/- 6 (mL/100 mL/min), 5.2 +/- 0.6 (mL/100 mL), 3.3 +/- 0.4 (mL/100 mL/min), and 0.39 +/- 0.05, respectively. With the exception of OEF, values differed between 2D PET and 3D PET. However, average gray matter values of scatter-corrected 3D PET were comparable to those of 2D PET: 55 +/- 11 (mL/100 mL/min), 3.7 +/- 0.5 (mL/100 mL), 3.8 +/- 0.7 (mL/100 mL/min), and 0.36 +/- 0.06, respectively. Even though the 2 PET scanners with different crystal materials, data acquisition systems, spatial resolution, and attenuation-correction methods were used, the agreement of the results between 2D PET and scatter-corrected 3D PET was excellent., Conclusion: Scatter coincidence is a problem in 3D PET for quantitative (15)O study. The combination of both the present PET/CT device and the HDE scatter correction permits quantitative 3D PET with the same degree of accuracy as 2D PET and with a lower radiation dose. The present scanner is also applicable to conventional steady-state (15)O gas inhalation if inhaled doses are adjusted appropriately.

Cerebral vascular mean transit time (MTT), defined as the ratio of cerebral blood volume to cerebral blood flow (CBV/CBF), is a valuable indicator of the cerebral circulation. Positron emission tomography (PET) and dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) are useful for the quantitative determination of MTT in the clinical setting. The aim of this study was to establish a normal value set of MTT as determined by PET and by DSC-MRI and to identify differences between these methods. Seven healthy volunteers were studied with (15)O-PET (H(2)(15)O and C(15)O) and gradient-echo echo-planar DSC-MRI at 1.5 T. In the DSC-MRI study with bolus injection of contrast agent, deconvolution analysis was performed. Comparison of gray-to-white matter ratios showed fairly good agreement between PET and DSC-MRI for all parameters (relative CBV, relative CBF, and relative MTT), confirming the validity of relative measurements with DSC-MRI. However, quantitative MTT measured by DSC-MRI was significantly shorter than that measured by PET in cerebral cortical regions (2.8 to 3.0 secs for DSC-MRI versus 3.9 to 4.3 secs for PET) and the centrum semiovale (3.5 secs for DSC-MRI versus 4.8 secs for PET). These discrepancies may be because of the differences in the intrinsic sensitivity of each imaging modality to vascular components; whereas PET measurement of CBV is equally sensitive to all vascular components, measurement with DSC-MRI originates from the microvasculature in the vicinity of the brain parenchyma. This underlying difference may influence interpretation of MTT determined by PET or by DSC-MRI for patients with cerebrovascular disease.

Background and Purpose: We can easily recognize familiar music by listening to only one or 2 of its opening bars, but the brain regions that participate in this cognitive processing remain undetermined. We used positron-emission tomography (PET) to study changes in regional cerebral blood flow (rCBF) that occur during listening to familiar music., Methods: We used a PET subtraction technique to elucidate the brain regions associated with the recognition of familiar melodies such as well-known nursery tunes. Nonmusicians performed 2 kinds of musical tasks: judging the familiarity of musical pieces (familiarity task) and detecting deliberately altered notes in the pieces (alteration-detecting task)., Results: During the familiarity task, bilateral anterior portions of bilateral temporal lobes, superior temporal regions, and parahippocampal gyri were activated. The alteration-detecting task bilaterally activated regions in the precunei, superior/inferior parietal lobules, and lateral surface of frontal lobes, which seemed to show a correlation with the analysis of music., Conclusion: We hypothesize that during the familiarity task, activated brain regions participate in retrieval from long-term memory and verbal and emotional processing of familiar melodies. Our results reinforced the hypothesis reported in the literature as a result of group and case studies, that temporal lobe regions participate in the recognition of familiar melodies.

Background and Purpose: We evaluated the effects of varying tube voltage, current per rotation, and section thickness on detectability of 2- and 4-Hounsfield unit (HU) differences on brain CT between normal and ischemic gray matter within 6 hours of ischemia onset, by using a low-contrast phantom., Methods: The phantom with an attenuation of 36 HU corresponding to normal gray matter contained 2 sets of spheres (34 HU and 32 HU) corresponding to the early CT signs of ischemic brain and complete infarction, respectively. The reproducibility of the CT numbers and the contrast-to-noise ratio (CNR), defined as the CT number difference between the background (36 HU) and the spheres (34 HU or 32 HU) divided by the SD of the background CT number were measured. Five radiologists rated the phantom images for detection of the low-contrast spheres by visual inspection., Results: The CT numbers were reproducible within 1 HU with a tube current of > or =150 mAs at 120 kVp. The CNRs for the 34- and 32-HU spheres were positively correlated with the tube voltage, tube current per rotation, and the section thickness. A CNR of 1.0 was obtained for the 34-HU sphere when scanning was conducted with a section thickness of 10 mm at 120 kVp and 700 mAs, or 135kVp and 450 mAs, respectively. A significant improvement of the accuracy of detection was found with increasing tube current, tube voltage per rotation, and section thickness., Conclusion: Our study indicated that the 2-HU hypoattenuation corresponding to the early CT sign of acute ischemic stroke can be detected by using appropriate parameter settings.

Volume expansion associated with brain infarction occurs in perfusion-diffusion mismatch of magnetic resonance imaging. We aimed at elucidating the metabolic impairment of this phenomenon with (15)O positron emission tomography and perfusion and diffusion magnetic resonance imaging. Eleven patients with acute unilateral embolic occlusion of the internal carotid or middle cerebral artery were studied within 6 hours of onset. Regional cerebral blood flow and cerebral metabolic rate of oxygen (CMRO(2)) were compared with those in the contralateral cerebral hemisphere. The relative apparent diffusion coefficient of water was estimated as a marker of cytotoxic edema. Relative cerebral blood flow and relative CMRO(2) in an evolving infarct (normal diffusion initially, but abnormal on day 3) were significantly (p < 0.05) less than those in the periinfarct area (normal diffusion initially and on day 3). The relative apparent diffusion coefficient between the evolving infarct and periinfarct showed no significant difference. These findings indicated that the initial 3-day volume expansion of an embolic brain infarction was associated with disturbed CMRD(2) but not with cytotoxic edema as early as 6 hours after onset. The "metabolic penumbra" defined as normal water diffusion with depressed CMRO(2) is a target to reduce the volume expansion of brain infarction.

Cerebral blood flow (CBF) and vascular mean transit time (MTT) can be determined by dynamic susceptibility contrast-enhanced magnetic resonance imaging and deconvolution with an arterial input function. However, deconvolution by a singular value decomposition (SVD) method is sensitive to the tracer delay that often occurs in patients with cerebrovascular disease. We investigated the effect of tracer delay on CBF determined by SVD deconvolution. Simulation study showed that underestimation of CBF due to tracer delay was larger for shorter MTTs. We developed a delay correction method that determines tracer delay by means of least-squares fitting pixel-by-pixel. The corrected CBF was determined by SVD deconvolution after time-shifting of the measured concentration curve. The simulations showed that the corrected CBF was insensitive to tracer delay irrespective of the vascular model, although CBF fluctuation increased slightly. We applied the delay correction to the CBF and MTT images acquired for nine patients with hyperacute stroke and unilateral occlusion of the middle cerebral artery. We found in some patients that the delay correction modulated the contrast of CBF and MTT images. For hyperacute stroke patients, tracer delay correction is essential to obtain reliable perfusion image when SVD deconvolution is used.

Purpose: Deconvolution based on truncated singular value decomposition (SVD deconvolution) is a promising method for measuring cerebral blood flow (CBF) with dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI), but it has proved extremely sensitive to tracer delay. The purpose of this study was to investigate the effect of regional tracer delay on CBF determined by SVD deconvolution (SVD-CBF). SVD-CBFs with and without correction for the delay were compared with CBF measured by positron emission tomography (PET-CBF), which is regarded as the gold standard for quantification of CBF., Methods: Perfusion MRI and PET were performed on seven healthy men. In the PET study, the CBF image was obtained with bolus injection of H2(15)O and continuous arterial sampling. In the DSC-MRI study with bolus injection of Gd-based contrast agent, dynamic perfusion data were obtained with a 1.5T scanner at 1-s intervals by means of gradient-echo echo-planar imaging. CBF was determined by the SVD deconvolution method with and without correction for the tracer delay. Region-of-interest measurements were obtained in the gray matter (cerebral cortex in the middle cerebral artery territory) and white matter (centrum semiovale)., Results: Tracer delay was significantly longer in white matter than in gray matter (1.45+/-0.61 s vs. 0.59+/-0.35 s, P<0.01). Correction for the delay increased SVD-CBF in the white matter and consequently reduced the gray-to-white SVD-CBF ratio. The uncorrected gray-to-white SVD-CBF ratio was significantly larger than that of PET-CBF (3.33+/-0.66 vs. 2.54+/-0.49, P<0.01). However, the gray-to-white delay-corrected SVD-CBF ratio did not differ significantly from that of PET-CBF (2.83+/-0.31 vs. 2.54+/-0.49, P=0.10)., Conclusion: The tracer delay in DSC-MRI causes errors in CBF estimates, even in healthy persons, and therefore should be corrected for when delay-sensitive deconvolution, such as SVD deconvolution, is used.

Unlabelled: A method for relative measurement of cerebral blood flow (CBF), oxygen extraction fraction (OEF), and metabolic rate of oxygen (CMRO2) using positron emission tomography (PET) without arterial sampling in patients with hyperacute ischemic stroke was presented., Methods: The method requires two PET scans, one for H2(15)O injection and one for 15O2 inhalation, and calculates regional CBF, CMRO2, and OEF relative to those at the reference brain region by means of table-lookup method. In this study, we calculated "relative lookup-tables" which relate relative CBF to relative H2(15)O count, relative CMRO2 to relative 15O2 count, and relative OEF to relative 15O2/H2(15)O count. Two assumptions were applied to the lookup-table calculation: 1) In the reference region. CBF and OEF were assumed to be 50.0 ml/min/100 ml and 0.40, respectively, 2) Cerebral blood volume (CBV) was assumed to be constant at 4.0 ml/100 ml over the whole brain. Simulation studies were done to estimate the error of the present method derived from the assumptions., Results: For relative CBF measurements, 20% variation in reference CBF gave about +/- 10% error for measured relative CBF at maximum. Changes in CBV caused relatively large errors in measured OEF and CMRO2 when relative CBF and OEF decreased. Errors for measured relative OEF caused by 50% variation in CBV were within +/- 8% at 0.8 of relative CBF and +/- 12% at 0.4 of relative CBF when relative OEF was greater than 1.0., Conclusion: CBV effects caused larger errors in estimated OEF and CMRO2 in the region of the ischemic core with decreasing relative CBF and/or OEF but only slight errors in the region of "misery perfusion" with relative OEF values greater than 1.0. The present method makes PET measurements simpler than with the conventional method and increases understanding of the cerebral circulation and oxygen metabolism in patients with hyperacute stroke of several hours after onset.

Hypercapnia and hypocapnia produce cerebral vasodilation and vasoconstriction, respectively. However, regional differences in the vascular response to changes in Paco2 in the human brain are not pronounced. In the current study, these regional differences were evaluated. In each of the 11 healthy subjects, cerebral blood flow (CBF) was measured using 15O-water and positron emission tomography at rest and during hypercapnia and hypocapnia. All CBF images were globally normalized for CBF and transformed into the standard brain anatomy. t values between rest and hypercapnia or hypocapnia conditions were calculated on a pixel-by-pixel basis. In the pons, cerebellum, thalamus, and putamen, significant relative hyperperfusion during hypercapnia was observed, indicating a large capacity for vasodilatation. In the pons and putamen, a significant relative hypoperfusion during hypocapnia, that is, a large capacity for vasoconstriction, was also observed, indicating marked vascular responsiveness. In the temporal, temporo-occipital, and occipital cortices, significant relative hypoperfusion during hypercapnia and significant relative hypoperfusion during hypocapnia were observed, indicating that cerebral vascular tone at rest might incline toward vasodilatation. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve by hypercapnia and in the correction of CBF measurements for variations in subjects' resting Paco2.

Pathophysiology of cerebrovascular disease has been studied by measuring cerebral blood flow and energy metabolism using single photon emission computed tomography (SPECT) and positron emission tomography (PET). These parameters are measures for brain tissue consisting of heterogeneous components such as neurons, glial cells, and blood vessels. It is still difficult to evaluate brain damages specifically involving either neurons or other components. Several trials were recently conducted to visualize neuron-specific injury in cerebrovascular disease by means of 11C flumazenil for PET and 123I-iomazenil for SPECT. These tracers selectively bind to central benzodiazepine receptor which is purely neuronal. A reduced accumulation of these ligands was found in the area surrounding the complete infarction and in the cortex remote from putaminal hemorrhage, indicating the existence of neuron specific injury not visualized by CT and MR. Neurological deficits were well correlated with the loss of cortical accumulation of these ligands. These preliminary studies indicated a potential of neurochemical imaging in cerebrovascular disease. Vulnerability to ischemia which may differ among brain tissue components, among subpopulations of neurons, and among pre-synaptic and post-synaptic functions can be more precisely examined. Neurochemical imaging can be also applied to reveal releases and re-organization of each neurotransmitter-acceptor system after stroke.

Background and Purpose: We examined whether hemodynamic and metabolic abnormalities in the cerebral white matter, basal ganglia, and thalamus are associated with asymptomatic white matter lesions (WML) depicted on MR images., Methods: A positron emission tomographic study with H2(15)O, C15O, and 15O2 was performed in eight normal control subjects without any WML (mean +/- 1 SD age, 68.5 +/- 10.2 years) and in 15 asymptomatic subjects with WML (71.3 +/- 8.5 years) to measure regional cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and oxygen metabolic rate., Results: In the cerebral white matter in the asymptomatic subjects with WML, significantly lower CBF (20.3 +/- 3.9 mL/100 mL per minute; P < .05) and significantly higher OEF (0.43 +/- 0.08; P < .05) were found compared with those for control subjects (23.5 +/- 2.6 mL/100 mL per minute and 0.37 +/- 0.06, respectively). The severity of WML was not related to the magnitude of hypoperfusion. In the basal ganglia, significantly lower CBF (44.9 +/- 6.9 mL/100 mL per minute; P < .01) and significantly higher OEF (0.54 +/- 0.08; P < .01) were found in the WML group than in control subjects (70.1 +/- 12.0 mL/100 mL/min and 0.39 +/- 0.03, respectively). In the thalamus, there was no significant difference in CBF and OEF between the control and WML groups., Conclusions: Hypoperfusion of the cerebral white matter and basal ganglia in asymptomatic WML subjects may be induced by the arteriosclerosis of long penetrating medullary arteries and lenticulostriate arteries but may not be directly related to the production of WML. The role of hypoperfusion in the production of WML and acceleration of its development remains to be elucidated.

Unlabelled: Discordant findings of 99mTc-methyl cysteinate dimer (99mTc-ECD) brain distribution have been reported when brain tissue is supplied by excess blood flow. We evaluated changes in 99mTc-ECD brain activity in the opposing pathological state, in which cerebral blood flow (CBF) is more profoundly impaired than metabolism, and analyzed the relationship of 99mTc-ECD activity with CBF and metabolism to investigate the dominant regulating factor on 99mTc-ECD distribution., Methods: Twelve patients with unilateral intracranial steno-occlusive diseases were evaluated using dynamic and static 99mTc-ECD SPECT. Relative 99mTc-ECD activities and the retention ratio of the affected and unaffected cortices were compared with CBF and oxygen metabolism obtained by PET. Change in the relationships until 1 hr after tracer injection were also analyzed., Results: Relative 99mTc-ECD activity was significantly correlated with CBF, and the highest correlation was obtained for the first minute of imaging (r = 0.674, p < 0.0010. Fifteen minutes after injection, the correlation coefficient with CBF decreased, whereas higher correlation was observed with the parameter of oxygen metabolism (r = 0.758-0.815, p < 0.001). Changes in the retention ratio were dependent on changes in oxygen metabolism, and the retention ratio for the high oxygen extraction fraction (OEF) area was the same as that for the normal OEF area., Conclusion: In addition to CBF, brain distribution on 99mTc-ECD SPECT images is affected by brain metabolism, especially on delayed images after injection. The degree of discrepancy between CBF and metabolism should be considered when interpreting images of the misery perfusion state.

Unlabelled: This study evaluates ischemic damage to central benzodiazepine (BZD) receptor binding in the brain with [123]iomazenil SPECT in relation to CT hypodense lesions and blood flow abnormalities., Methods: Nine patients with middle cerebral artery territory infarction were studied. Iomazenil images obtained 180 min postinjection were analyzed for BZD receptor binding. The cortical infraction, visualized as CT hypodense area on CT, the peri-infarct area, visualized as normodensity surrounding the infarction on CT, the intrahemispheric remote area and the cerebellum were analyzed by taking the ratio of the lesion to contralateral mirror region (L/C ratio). CT during the chronic stage and perfusion images obtained during the smallest time difference between the two studies were used for comparative analysis., Results: The mean L/C ratio of iomazenil uptake was 0.53 +/&#95; 0.08, 0.79 +/- 0.07, 0.98 +/- 0.03 and 1.00 +/- 0.04 in the infarct, peri-infarct and remote areas and the cerebellum, respectively. The infarct and peri-infarct areas showed significant decrease compared with unity. The corresponding mean L/C ratio for blood flow was 0.52 +/- 0.08, 0.73 +/- 0.07, 0.83 +/- 0.09, and 0.80 +/- 0.07, respectively. In all areas, the ratios were significantly decreased compared with unity. There was significant difference between the L/C ratio for blood flow and iomazenil in the remote area and the cerebellum., Conclusion: Iodine-123-iomazenil SPECT imaging may provide new information on ischemic damage to the brain, particularly neurons.

Three patients with subacute ischemic cerebral infarction examined by SPECT with 99mTc-ECD and PET within the same day showed signs of luxury perfusion in the subacute phase, which is between 9 to 20 days after the onset. A 99mTc-HMPAO SPECT study was also performed within 2 days of the ECD-SPECT study. ECD-SPECT images of three patients displayed a focal decreased uptake in the infarcted lesions, while in infarcted foci, there was almost equivalent or increased CBF compared to normal and unaffected areas, decreased CMRO2, and high HMPAO uptake. The ECD-SPECT results were similar to those of CMRO2 rather than CBF, though the HMPAO-SPECT image was similar to that of CBF. In one patient, HMPAO images revealed hyperfixation of the tracer. In the chronic phase and in the acute phase before 5 days after the onset, there were no discrepancies among the ECD-SPECT, CBF, HMPAO-SPECT, and CMRO2 images. These observations indicated that 99mTc-ECD is a good indicator of damaged brain tissues in subacute ischemic infarction. They also suggested that 99mTc-ECD is a potential agent with which to evaluate cerebral tissue viability in some pathological states of cerebrovascular disease. The characteristics may be suitable for confirming the effects of thrombolytic therapy in acute ischemia, because these conditions often show signs of luxury perfusion when the therapy is successful.

The degree of collateral circulation in patients with unilaterally chronic internal carotid artery occlusion was estimated by mean transit time of contrast material in rapid sequence carotid angiography (Angiographic MTT), and compared with cerebral blood flow and oxygen metabolism measured by PET. In normal density region on X-ray CT, a significant negative correlation was observed between Angiographic MTT and cerebral blood flow (CBF). This indicates that cerebral blood flow can be estimated by Angiographic MTT. It has been reported that the ratio of cerebral blood volume (CBV) to CBF (CBV/CBF), i.e., mean transit time determined by PET well agreed with OEF, and is good indicator for brain circulation reserve. In this study, no significant correlation was observed between Angiographic MTT and CBV/CBF. However, a significant positive correlation was observed between Angiographic MTT and oxygen extraction fraction (OEF), and no significant correlation was observed between Angiographic MTT and oxygen consumption rate (CMRO2). These indicates that Angiographic MTT may be indicator for brain circulation reserve.

Unlabelled: Technetium-99m-HMPAO can be used to evaluate abnormal brain perfusion in the hyperacute stage of stroke., Methods: We investigated cerebral blood flow using 99mTc-HMPAO SPECT in 31 patients within 6 hr after the onset of cerebral infarction and analyzed the relationship between abnormal perfusion and morphological changes on follow-up CT scans. Patients were classified into an infarct group and a noninfarct group, and the lesions on SPECT images were divided into infarct and peri-infarct regions., Results: Among a total of 30 infarct regions, three lesions studied at 1.5, 2.5 and 5 hr after the ictus showed local hyperperfusion suggestive of early postischemic hyperemia, while the other 27 lesions demonstrated local hypoperfusion. All of the peri-infarct regions showed moderate hypoperfusion. The noninfarct group consisted of five patients, four of whom showed no perfusion abnormalities. The lesion-to-contralateral radioactivity ratios for the infarct and peri-infarct regions were respectively 0.48 +/- 0.14 and 0.75 +/- 0.10 in the patients with hypoperfusion, while the right-to-left ratio in the noninfarct group was 0.97 +/- 0.10., Conclusion: This SPECT study of cerebral blood flow demonstrates that local hyperperfusion occurs in some infarcts even within 6 hr of onset and that infarcted and morphological viable brain can be distinguished by a lesion-to-contralateral radioactivity ratio of 0.6 within this time range.

The regional brain uptake of 99mTc-N,N'-(1,2-ethylenediyl)bis-L-cysteine diethyl ester (99mTc-bicisate) measured by single photon emission computed tomography (SPECT) was compared with the regional CBF and CMRO2 measured by positron emission tomography in patients with cerebrovascular disease. Nine patients with the diagnosis of cerebral ischemic disorders (n = 7) or cerebral hemorrhage (n = 2) were studied. 99mTc-Bicisate brain uptake correlated with CBF and CMRO2. However, 99mTc-bicisate uptake did not reflect CBF in the single lesion showing luxury perfusion, which seemed to resemble a CMRO2 image. Though quantitative analysis showed the nonlinear correspondence of 99mTc-bicisate brain uptake with CBF and CMRO2, this correspondence could be corrected into a more linear relationship using a correction factor. 99mTc-Bicisate washout from the brain had no correlation to CBF and CMRO2. This diffuse decreasing washout rate was approximately 15% during the first hour after injection. By using the lipophilic fraction of arterial blood and a linearized correction of 99mTc-bicisate SPECT images, the feasibility of obtaining a factor-related CBF and CMRO2 was suggested from our data. These results suggested that 99mTc-bicisate had good characteristics for routine clinical use with SPECT to display the brain function in patients with neurological disorders.

Objective: MR imaging has a high sensitivity for detecting ischemic brain parenchyma. The aim of this study was to evaluate the changes in the signal intensity of infarcted brain parenchyma on MR images obtained within the first 3 hr after the onset of signs and symptoms in patients with embolic cerebral infarction., Materials and Methods: We studied MR images of 16 patients who had a diagnosis of embolic cerebral infarction (highly probable according to criteria of the National Institute of Neurological and Communicative Disorders and Stroke). T1-weighted, T2-weighted, and proton density-weighted MR images were obtained within 3 hr after the onset of symptoms. Two neuroradiologists who had no knowledge of the diagnoses reviewed the MR images of these 16 patients and 20 control subjects in random order and evaluated signal-intensity changes in the gray and white matter., Results: On proton density-weighted images, the central and cortical gray matter showed increased signal intensity in 63-69% and 88-94% of the patients, respectively. No abnormalities of the brain parenchyma were apparent on T1-weighted and T2-weighted images obtained within 3 hr after the onset of symptoms. The adjacent white matter appeared hyperintense on long TR images in only a few cases., Conclusion: An increased signal intensity in the gray matter on proton density-weighted images was the most characteristic parenchymal change seen on MR images of the brain obtained within 3 hr after embolic cerebral infarction.

Technetium-99m ethyl cysteinate dimer (ECD) has recently developed for SPECT imaging in assessment of cerebral perfusion. We evaluated the arterial blood clearance and the regional brain uptake of Tc-99m ECD compared with the regional CBF measured by PET in patients with cerebrovascular disease. Nine patients with diagnosis of cerebral ischemic disorders (N = 7) and cerebral hemorrhage (N = 2) were studied. PET study was performed with HEADTOME IV by O-15 steady state inhalation method. Immediately after the PET study, 555-740 MBq (5-20 mCi) of Tc-99m ECD was injected intravenously. After injection arterial blood sampling was performed sequentially, and we separated lipophilic fraction from whole blood using ethyl acetate in two cases. The SPECT imaging with Tc-99m ECD (ECD-SPECT) was started 5 min (first imaging) and 60 min (second imaging) after the administration using a high resolution ring type SPECT system (HEADTOME II). Several ROIs were placed on practically the same anatomical location on both SPECT and PET images. Clearance of the tracer in arterial whole blood and lipophilic fraction was rapid. Concerning to the distribution pattern of ECD-SPECT images there was no differences between the 1st imaging and the 2nd imaging, although about 15% of diffuse decrease of Tc-99m ECD uptake was shown in the 2nd images. The brain distribution of ECD-SPECT was comparable to the pattern of CBF image by PET. The regional relative counts of ECD-SPECT corresponded closely to the CBF value by PET, but it was no linear correlation between brain uptake of ECD-SPECT and PET-CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

In quantitative functional neuroimaging with positron emission tomography (PET) and magnetic resonance imaging (MRI), cerebral blood volume (CBV) and its three components, arterial, capillary, and venous blood volumes are important factors. The arterial fraction for systemic circulation of the whole body has been reported to be 20-30%, but there is no report of this fraction in the brain. In the present study, we estimated the arterial fraction of CBV with PET in the living human brain. C(15)O and dynamic H2(15)O PET studies were performed in each of seven healthy subjects to determine the CBV and arterial blood volume (Va), respectively. A two-compartment model (influx: K1, efflux: k2) that takes Va into account was applied to describe the regional time-activity curve of dynamic H2(15)O PET. K1, k2 and Va were calculated by a non-linear least squares fitting procedure. The Va and CBV values were 0.011 +/- 0.004 ml/ml and 0.031 +/- 0.003 ml/ml (mean +/- SD), respectively, for cerebral cortices. The arterial fraction of CBV was 37%. Considering the limited first-pass extraction fraction of H2(15)O, the true arterial fraction of CBV is estimated to be about 30%. The estimated arterial fraction of CBV was quite similar to that of the systemic circulation, whereas it was greater than that (16%) widely used for the measurement of cerebral metabolic rate of oxygen (CMRO2) using PET. The venous plus capillary fraction of CBV was 63-70% which is a important factor for the measurement of CMRO2 with MRI. [ABSTRACT FROM AUTHOR]