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Abstract In Myocardial Perfusion Imaging (MPI) with Positron Emission Tomography/Computed Tomography (PET/CT) systems, accurate quantification is essential. We assessed flow quantification accuracy over various injected activities using a flow phantom. Methods The study was performed on the digital 4-ring Discovery MI (DMI-20) and analog Discovery 690 (D690) PET/CT systems, using 325-1257 MBq of [15O]H2O. PET performance and flow quantification accuracy were assessed in terms of count-rates, dead-time factors (DTF), scatter fractions (SF), time-activity curves (TACs), areas-under-the-curves (AUCs) and flow values. Results On DMI-20, prompts of 12.8 Mcps, DTF of 2.06 and SF of 46.1% were measured with 1257 MBq of activity. On the D690, prompts of 6.85 Mcps, DTF of 1.57 and SF of 32.5% were measured with 1230 MBq of activity. AUC values were linear over all activities. Mean wash-in flow error was − 9% for both systems whereas wash-out flow error was − 5% and − 6% for DMI-20 and D690. With the highest activity, wash-out flow error was − 12% and − 7% for the DMI-20 and D690. Conclusion DMI-20 and D690 preserved accurate flow quantification over all injected activities, with maximum error of − 12%. In the future, flow quantification accuracy over the activities and count-rates evaluated in this study should be assessed.

Perinatal hypoxic ischemic encephalopathy (HIE) results in serious neurological dysfunction and mortality. Clinical trials of multilineage-differentiating stress enduring cells (Muse cells) have commenced in stroke using intravenous delivery of donor-derived Muse cells. Here, we investigated the therapeutic effects of human Muse cells in an HIE model. Seven-day-old rats underwent ligation of the left carotid artery then were exposed to 8% oxygen for 60 min, and 72 hours later intravenously transplanted with 1 × 104 of human-Muse and -non-Muse cells, collected from bone marrow-mesenchymal stem cells as stage-specific embryonic antigen-3 (SSEA-3)+ and −, respectively, or saline (vehicle) without immunosuppression. Human-specific probe revealed Muse cells distributed mainly to the injured brain at 2 and 4 weeks, and expressed neuronal and glial markers until 6 months. In contrast, non-Muse cells lodged in the lung at 2 weeks, but undetectable by 4 weeks. Magnetic resonance spectroscopy and positron emission tomography demonstrated that Muse cells dampened excitotoxic brain glutamatergic metabolites and suppressed microglial activation. Muse cell-treated group exhibited significant improvements in motor and cognitive functions at 4 weeks and 5 months. Intravenously transplanted Muse cells afforded functional benefits in experimental HIE possibly via regulation of glutamate metabolism and reduction of microglial activation.

PET with (18)F-FDG has been increasingly applied, predominantly in the research setting, to study drug effects and pulmonary biology and to monitor disease progression and treatment outcomes in lung diseases that interfere with gas exchange through alterations of the pulmonary parenchyma, airways, or vasculature. To date, however, there are no widely accepted standard acquisition protocols or imaging data analysis methods for pulmonary (18)F-FDG PET/CT in these diseases, resulting in disparate approaches. Hence, comparison of data across the literature is challenging. To help harmonize the acquisition and analysis and promote reproducibility, we collated details of acquisition protocols and analysis methods from 7 PET centers. From this information and our discussions, we reached the consensus recommendations given here on patient preparation, choice of dynamic versus static imaging, image reconstruction, and image analysis reporting.

BackgroundDespite improvement in short-term outcome of kidney transplants, the long-term survival of kidney transplants has not changed over past decades. Kidney biopsy is the gold standard of transplant pathology but it’s invasive. Quantification of transplant blood flow could provide a novel non-invasive method to evaluate transplant pathology. The aim of this retrospective cross-sectional pilot study was to evaluate positron emission tomography (PET) as a method to measure kidney transplant perfusion and find out if there is correlation between transplant perfusion and histopathology.MethodsRenal cortical perfusion of 19 kidney transplantation patients [average time from transplantation 33 (17–54) months; eGFR 55 (47–69) ml/min] and 10 healthy controls were studied by [15O]H2O PET. Perfusion and Doppler resistance index (RI) of transplants were compared with histology of one-year protocol transplant biopsy.ResultsRenal cortical perfusion of healthy control subjects and transplant patients were 2.7 (2.4–4.0) ml min− 1 g− 1and 2.2 (2.0–3.0) ml min− 1 g− 1, respectively (p = 0.1). Renal vascular resistance (RVR) of the patients was 47.0 (36.7–51.4) mmHg mL− 1min− 1g− 1and that of the healthy 32.4 (24.6–39.6) mmHg mL− 1min−1g−1(p = 0.01). There was a statistically significant correlation between Doppler RI and perfusion of transplants (r = − 0.51,p = 0.026). Transplant Doppler RI of the group of mild fibrotic changes [0.73 (0.70–0.76)] and the group of no fibrotic changes [0.66 (0.61–0.72)] differed statistically significantly (p = 0.03). No statistically significant correlation was found between cortical perfusion and fibrosis of transplants (p = 0.56).Conclusions[15O]H2O PET showed its capability as a method in measuring perfusion of kidney transplants. RVR of transplant patients with stage 2–3 chronic kidney disease was higher than that of the healthy, although kidney perfusion values didn’t differ between the groups. Doppler based RI correlated with perfusion and fibrosis of transplants.

Human studies of renal hemodynamics and metabolism in obesity are insufficient. We hypothesized that renal perfusion and renal free fatty acid (FFA) uptake are higher in subjects with morbid obesity compared with lean subjects and that they both decrease after bariatric surgery. Cortical and medullary hemodynamics and metabolism were measured in 23 morbidly obese women and 15 age- and sex-matched nonobese controls by PET scanning of [15O]-H2O (perfusion) and 14( R,S)-[18F]fluoro-6-thia-heptadecanoate (FFA uptake). Kidney volume and radiodensity were measured by computed tomography, cardiac output by MRI. Obese subjects were re-studied 6 mo after bariatric surgery. Obese subjects had higher renal volume but lower radiodensity, suggesting accumulation of water and/or lipid. Both cardiac output and estimated glomerular filtration rate (eGFR) were increased by ~25% in the obese. Total renal blood flow was higher in the obese [885 (317) (expressed as median and interquartile range) vs. 749 (300) (expressed as means and SD) ml/min of controls, P = 0.049]. In both groups, regional blood perfusion was higher in the cortex than medulla; in either region, FFA uptake was ~50% higher in the obese as a consequence of higher circulating FFA levels. Following weight loss (26 ± 8 kg), total renal blood flow was reduced ( P = 0.006). Renal volume, eGFR, cortical and medullary FFA uptake were decreased but not fully normalized. Obesity is associated with renal structural, hemodynamic, and metabolic changes. Six months after bariatric surgery, the hemodynamic changes are reversed and the structural changes are improved. On the contrary, renal FFA uptake remains increased, driven by high substrate availability.

While brown adipose tissue (BAT) activity is known to be associated with both muscle and adipose tissue volumes, the association between BAT and muscle composition remains unclear, especially in adults. Therefore, the present study aimed to examine the association between BAT parameters (glucose uptake and fat-fraction) and muscle volumes and intramuscular adipose tissue contents among healthy young and middle-aged men.BAT glucose uptake was determined using positron emission tomography with [The fat-fraction of BAT was significantly associated with intramuscular adipose tissue content in m. tibialis anterior (n = 13, rThe fat-fraction of BAT increases with skeletal muscle adiposity, especially in the lower leg, among healthy young and middle-aged men.

As matrix metalloproteinases (MMPs), especially MMP-9 and MMP-12 are involved in the pathological processes associated with chronic obstructive pulmonary disease (COPD), we developed a novel radiofluorinated probe, 18F-IPFP, for MMPs-targeted positron emission tomography (PET). 18F-IPFP was designed by iodination of MMP inhibitor to enhance the affinity, and labelled with a compact prosthetic agent, 4-nitrophenyl 2-18F-fluoropropionate (18F-NFP). As a result, IPFP demonstrated the highest affinity toward MMP-12 (IC50 = 1.5 nM) among existing PET probes. A COPD model was employed by exposing mice to cigarette smoke and the expression levels of MMP-9 and MMP-12 were significantly increased in the lungs. Radioactivity accumulation in the lungs 90 min after administration of 18F-IPFP was 4× higher in COPD mice than normal mice, and 10× higher than in the heart, muscle, and blood. Ex vivo PET confirmed the radioactivity distribution in the tissues and autoradiography analysis demonstrated that accumulation differences in the lungs of COPD mice were 2× higher than those of normal mice. These results suggest that 18F-IPFP is a promising probe for pulmonary imaging and expected to be applied to various MMP-related diseases for early diagnosis, tracking of therapeutic effects, and new drug development in both preclinical and clinical applications.

Objective A direct causal relationship of cerebrovascular risk factors/stroke to amyloid β (Aβ) deposition has yet to be shown. We conducted [11 C] Pittsburgh compound B (PiB)-positron emission tomography (PET) analysis on subacute ischemic stroke patients and healthy controls. We hypothesized that subacute ischemic stroke patients would show focal Aβ accumulation in cortical regions, which would increase and extend over time during the chronic phase after stroke onset. Methods Patients were recruited 14 to 28 days after acute subcortical ischemic stroke and examined with [11 C]PiB-PET scans. Regional time-activity data were analyzed with the Logan graphical method. Whole brain voxel-based analysis was conducted to compare stroke patients with healthy controls. We also performed longitudinal comparison of patients with successive [11 C]PiB-PET scans 1 year after stroke. Results Voxel-based analysis revealed a significant increase of [11 C]PiB-BPND of the precuneus/posterior cingulate cortex (PCu/PCC) in stroke patients at the subacute stage. Based on stepwise multiple regression analysis of [11 C]PiB-BP changes during follow-up as the dependent variable, years of education was the best independent correlate. There was a significant negative relationship between changes in [11 C]PiB-BP and years of education. Conclusions Our results suggest that processes before and after the onset of ischemic stroke may trigger Aβ deposition in the PCu/PCC, whereby amyloid deposition begins at an early stage of Alzheimer's disease (AD). Our findings support the existence of a cooperative association between vascular risk factors/stroke and AD progression. Further, educational achievement had a protective effect against the increase in Aβ accumulation.

Positron emission tomography (PET) remains the gold standard for quantitative imaging of the cerebral metabolic rate of oxygen (CMRO2); however, it is an invasive and complex procedure that requires accounting for recirculating [15O]H2O (RW) and the cerebral blood volume (CBV). This study presents a non-invasive reference-based technique for imaging CMRO2 that was developed for PET/magnetic resonance imaging (MRI) with the goal of simplifying the PET procedure while maintaining its ability to quantify metabolism. The approach is to use whole-brain (WB) measurements of oxygen extraction fraction (OEF) and cerebral blood flow (CBF) to calibrate [15O]O2-PET data, thereby avoiding the need for invasive arterial sampling. Here we present the theoretical framework, along with error analyses, sensitivity to PET noise and inaccuracies in input parameters, and initial assessment on PET data acquired from healthy participants. Simulations showed that neglecting RW and CBV corrections caused errors in CMRO2 of less than ±10% for changes in regional OEF of ±25%. These predictions were supported by applying the reference-based approach to PET data, which resulted in remarkably similar CMRO2 images to those generated by analyzing the same data using a modeling approach that incorporated the arterial input functions and corrected for CBV contributions. Significant correlations were observed between regional CMRO2 values from the two techniques (slope = 1.00 ± 0.04, R 2 > 0.98) with no significant differences found for integration times of 3 and 5 min. In summary, results demonstrate the feasibility of producing quantitative CMRO2 images by PET/MRI without the need for invasive blood sampling.

The ratio of signal intensity in T1-weighted (T1w) and T2-weighted (T2w) magnetic resonance imaging (MRI) was recently proposed to enhance the sensitivity of detecting changes in disease-related signal intensity. The objective of this study was to test the effectiveness of T1w/T2w image ratios as an easily accessible biomarker for amyloid beta (Aβ) accumulation. We performed the T1w/T2w analysis in cognitively normal elderly individuals. We applied [11C] Pittsburgh Compound B (PiB)-PET to the same individuals, and Aβ deposition was quantified by its binding potential (PiB-BPND). The subjects were divided into low and high PiB-BPND groups, and group differences in regional T1w/T2w values were evaluated. In the regions where we found a significant group difference, we conducted a correlation analysis between regional T1w/T2w values and PiB-BPND. Subjects with high global cortical PiB-BPND showed a significantly higher regional T1w/T2w ratio in the frontal cortex and anterior cingulate cortex. We found a significant positive relationship between the regional T1w/T2w ratio and Aβ accumulation. Moreover, with a T1w/T2w ratio of 0.55 in the medial frontal regions, we correctly discriminated subjects with high PiB-BPND from the entire subject population with a sensitivity of 84.6% and specificity of 80.0%. Our results indicate that early Aβ-induced pathological changes can be detected using the T1w/T2w ratio on MRI. We believe that the T1w/T2w ratio is a prospective stable biological marker of early Aβ accumulation in cognitively normal individuals. The availability of such an accessible marker would improve the efficiency of clinical trials focusing on the initial disease stages by reducing the number of subjects who require screening by Aβ-PET scan or lumbar puncture., Graphical abstract Image 1, Highlights • We examined the T1w/T2w ratio of MR images in cognitively normal elderly subjects. • Aβ deposition was quantified by [11C] PiB-PET binding potential (PiB-BPND). • The T1w/T2w ratios were positively correlated with PiB-BPND values. • We correctly discriminated subjects with high PIB-BPND using the T1w/T2w ratio. • The T1w/T2w ratio from MRI is a potential biological marker of early Aβ deposition.

Bypass surgery for complex intracranial aneurysms (IAs) results in drastic blood flow changes in intracranial arteries. The aim of the study was to elucidate how vessels adapt to blood flow changes after bypass surgery with phase-contrast magnetic resonance imaging (PC-MRI). This is a prospective observational study to assess changes of the blood flow in intracranial arteries after bypass surgery for IAs. Flow rates and vessel diameters were measured with PC-MRI in 52 intracranial arteries of 7 healthy volunteers and 31 arteries of 8 IA patients who underwent bypass surgery. Wall shear stress (WSS) was calculated with the Hagen-Poiseuille formula. In 18 arteries of 5 patients, the same measurement was performed 1, 3, and 12 months after surgery. PC-MRI showed a strong positive correlation between the flow rate and the third power of vessel diameter in both healthy volunteers (r = 0.82, P

RNF213 is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role of RNF213 in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils on Rnf213 knockout (KO) and vascular endothelial cell-specific Rnf213 mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice. Temporal CBF changes were measured by arterial spin-labelling magnetic resonance imaging. In the cortical area, no significant difference in CBF was found before surgery between the genotypes. Three of eight (37.5%) KO mice died after surgery but all wild-type and EC-Tg mice survived hypoperfusion. KO mice had a significantly more severe reduction in CBF on day 7 than wild-type mice (KO, 29.7% of baseline level; wild-type, 49.3%; p = 0.038), while CBF restoration on day 28 was significantly impaired in both KO (50.0%) and EC-Tg (56.1%) mice compared with wild-type mice (69.5%; p = 0.031 and 0.037, respectively). Changes in the subcortical area also showed the same tendency as the cortical area. Additionally, histological analysis demonstrated that angiogenesis was impaired in both EC-Tg and KO mice. These results are indicative of the essential role of RNF213 in the maintenance of CBF.

PURPOSE The aim of this study was to evaluate the effects of inaccurate attenuation correction due to the misalignment between the computed tomography (CT)-based μ-map and the positron emission tomography (PET) data on a brain PET. METHODS CT and PET scans were performed on a 3-dimension (3D) brain phantom, in which the grey matter region was filled with 18F-fluorodeoxyglucose (18F-FDG), and the skull region was filled with/without the bone-equivalent solution. The shifted PET images relative to the CT image were generated by the software-based translation of PET data in the cephalad/caudal and right directions, with a magnitude of the shift up to 30 mm and a step size of 5 mm. The regions of interest (ROIs) were drawn on the areas of the temporal lobes, parietal lobes, thalami, and cerebellums in the no-shifted image (reference). For each ROI, the radioactivity concentrations in the shifted images were compared with those of the reference. RESULTS The errors in the radioactivity concentrations were increased with the increasing magnitude of the shift in all brain regions except for thalamus. For a 5 mm shift in the right direction, ± 10% errors were observed in the left/right temporal lobes. The accuracy of the radioactivity concentration in the temporal lobe was very sensitive to misalignment in the right directions. CONCLUSION The misalignment between CT-based μ-map and PET data had larger effects on the surface regions of the brain rather than on deep brain structures.

Subjective cognitive impairment (SCI) is a clinical state characterized by subjective cognitive deficits without cognitive impairment. To test the hypothesis that this state might involve dysfunction of self-referential processing mediated by cortical midline structures, we investigated abnormalities of functional connectivity in these structures in individuals with SCI using resting-state functional magnetic resonance imaging. We performed functional connectivity analysis for 23 individuals with SCI and 30 individuals without SCI. To reveal the pathophysiological basis of the functional connectivity change, we performed magnetic resonance-diffusion tensor imaging. Positron emission tomography-amyloid imaging was conducted in 13 SCI and 15 nonSCI subjects. Individuals with SCI showed reduced functional connectivity in cortical midline structures. Reduction in white matter connections was related to reduced functional connectivity, but we found no amyloid deposition in individuals with SCI. The results do not necessarily contradict the possibility that SCI indicates initial cognitive decrements, but imply that reduced functional connectivity in cortical midline structures contributes to overestimation of the experience of forgetfulness.

Use of 15O labeled oxygen (15O2) and positron emission tomography (PET) allows quantitative assessment of the regional metabolic rate of oxygen (CMRO2) in vivo, which is essential to understanding the pathological status of patients with cerebral vascular and neurological disorders. The method has, however, been challenging, when a 3D PET scanner is employed, largely attributed to the presence of gaseous radioactivity in the trachea and the inhalation system, which results in a large amount of scatter and random events in the PET assessment. The present study was intended to evaluate the adequacy of using a recently available commercial 3D PET scanner in the assessment of regional cerebral radioactivity distribution during an inhalation of 15O2. Systematic experiments were carried out on a brain phantom. Experiments were also performed on a healthy volunteer following a recently developed protocol for simultaneous assessment of CMRO2 and cerebral blood flow, which involves sequential administration of 15O2 and C15O2. A particular intention was to evaluate the adequacy of the scatter-correction procedures. The phantom experiment demonstrated that errors were within 3% at the practically maximum radioactivity in the face mask, with the greatest radioactivity in the lung. The volunteer experiment demonstrated that the counting rate was at peak during the 15O gas inhalation period, within a verified range. Tomographic images represented good quality over the entire FOV, including the lower part of the cerebral structures and the carotid artery regions. The scatter-correction procedures appeared to be important, particularly in the process to compensate for the scatter originating outside the FOV. Reconstructed images dramatically changed if the correction was carried out using inappropriate procedures. This study demonstrated that accurate reconstruction could be obtained when the scatter compensation was appropriately carried out. This study also suggested the feasibility of using a state-of-the-art 3D PET scanner in the quantitative PET imaging during inhalation of 15O labeled oxygen.

The aim of the study was to investigate the existence of microstructural abnormalities in the white matter of the brain in stroke patients, as well as the relationship between these microstructural abnormalities and changes in depressive symptoms over 6 months. Participants were 29 acute ischemic stroke patients and 37 healthy control subjects. Depressive symptoms were assessed in all subjects using the Hamilton Rating Scale for Depression and the Zung Self-rating Depression Scale. Whole brain voxel-based analysis was used to compare diffusion tensor imaging measures of Fractional Anisotropy (FA) between the groups. Six-month follow-up examinations were conducted. Patients showed significantly lower white matter FA values in the left and right anterior limbs of the internal capsule, and 6 months after the stroke they showed significantly increased FA values in these regions. We found a significant negative correlation between the increased ratio of the FA values and the change in depression scale scores at 6-month follow-up. Regional white matter damage may reflect abnormalities in neuroanatomical pathways related to the pathophysiology of depression.

Twenty-one hypertensive vasculopathy patients, without AD and major cerebral arterial stenosis and/or occlusion, were enrolled (9 women, 68 ± 7 years). Regions of WML and NAWM were extracted using magnetization-prepared rapid gradient-echo and fluid-attenuated inversion recovery of magnetic resonance images. Volumes of interest (VOIs) were set in the cortex-subcortex, basal ganglia, and centrum semiovale (CS). BPBP

We hypothesized that cerebral amyloid accumulation is reflected in the periphery in the pre-dementia stage and used flow cytometry to investigate the peripheral lymphocytes as an easily accessible biomarker to observe neuro-inflammation. We aimed to determine whether peripheral lymphocytes are related to the cortical amyloid burden or vice versa in cognitively normal older subjects.We applied [Our results indicated that a specific peripheral immune response, reflected in the increased ratio of cytotoxic T cells, could be regarded as a preclinical sign of AD and could be attributed to the Aβ neuropathological mechanism. Copyright © 2017 John WileySons, Ltd.

Repeated stressful events are associated with the onset of major depressive disorder (MDD). We previously showed oligodendrocyte (OL)-specific activation of the serum/glucocorticoid-regulated kinase (SGK)1 cascade, increased expression of axon-myelin adhesion molecules and elaboration of the oligodendrocytic arbor in the corpus callosum of chronically stressed mice. In the current study, we demonstrate that the nodes and paranodes of Ranvier in the corpus callosum were narrower in these mice. Chronic stress also led to diffuse redistribution of Caspr and Kv 1.1 and decreased the activity in white matter, suggesting a link between morphological changes in OLs and inhibition of axonal activity. OL primary cultures subjected to chronic stress resulted in SGK1 activation and translocation to the nucleus, where it inhibited the transcription of metabotropic glutamate receptors (mGluRs). Furthermore, the cAMP level and membrane potential of OLs were reduced by chronic stress exposure. We showed by diffusion tensor imaging that the corpus callosum of patients with MDD exhibited reduced fractional anisotropy, reflecting compromised white matter integrity possibly caused by axonal damage. Our findings suggest that chronic stress disrupts the organization of the nodes of Ranvier by suppressing mGluR activation in OLs and that specific white matter abnormalities are closely associated with MDD onset.

Background Existing rodent models of vascular cognitive impairment (VCI) show abrupt changes in cerebral blood flow (CBF) and do not reliably replicate the clinical pathogenesis of VCI. We therefore aimed to develop a mouse model of VCI where CBF is gradually reduced, followed by subsequent progressive motor and cognitive impairment, after surgical intervention. Methods and Results Adult C57BL/6J male mice were subjected to gradual common carotid artery stenosis (GCAS) surgery by using an ameroid constrictor vessel‐constricting device with an inner diameter of 0.75 mm. The common carotid arteries narrowed gradually after gradual constriction of ameroid constrictors over 28 days after GCAS, with subsequent 79.3% area stenosis as a result of smooth muscle cell proliferation and macrophage infiltration in the tunica intima. The 28‐day survival rate was 91%. Arterial spin labeling demonstrated gradual and continuous reduction of cortical and subcortical CBF (ratio to the preoperative value) to 54.6% and 51.5%, respectively, over 28 days. However, magnetic resonance angiography showed increment of collateral flow signals in the leptomeningeal artery. Rarefaction and proliferation of astrocytes and microglia, with loss of oligodendrocytes, were found in the white matter at 32 days. Hippocampal neuronal loss was observed in only 25% of GCAS mice, consistent with lack of abnormalities in the Morris water maze test. The rotarod test showed motor impairment, and the Y‐maze test showed working memory deficits. Conclusions The GCAS model successfully generated gradual and continuous CBF reduction over 28 days, with replication of key histological, radiological, and behavioral features associated with cerebral hypoperfusion leading to VCI.

In clinical cardiac positron emission tomography using (15)O-water, significant tracer accumulation is observed not only in the heart but also in the liver and lung, which are partially outside the field-of-view. In this work, we investigated the effects of scatter on quantitative myocardium blood flow (MBF) and perfusable tissue fraction (PTF) by a precise Monte Carlo simulation (Geant4) and a numerical human model. We assigned activities to the heart, liver, and lung of the human model with varying ratios of organ activities according to an experimental time activity curve and created dynamic sinograms. The sinogram data were reconstructed by filtered backprojection. By comparing a scatter-corrected image (SC) with a true image (TRUE), we evaluated the accuracy of the scatter correction. TRUE was reconstructed using a scatter-eliminated sinogram, which can be obtained only in simulations. A scatter-uncorrected image (W/O SC) and an attenuation-uncorrected image (W/O AC) were also constructed. Finally, we calculated MBF and PTF with a single tissue-compartment model for four types of images. As a result, scatter was corrected accurately, and MBFs derived from all types of images were consistent with the MBF obtained from TRUE. Meanwhile, the PTF of only the SC was in agreement with the PTF of TRUE. From the simulation results, we concluded that quantitative MBF is less affected by scatter and absorption in 3D-PET using (15)O-water. However, scatter correction is essential for accurate PTF.

Objectives 15O-water-perfusable tissue fraction (PTF) has been shown to be a potential index for assessing myocardial viability in PET, an alternative to 18F-fluorodeoxyglucose (FDG). This study aimed to directly compare these two independent methods in assessing myocardial viability in patients with abnormal wall motion. Methods PET study was performed on 16 patients with previous myocardial infarction, before coronary artery bypass graft operation (CABG). The protocol included a 15O-carbonmonoxide static, a 15O-water dynamic and an 18F-FDG dynamic scan, during the euglycemic hyperinsulinemic clamp. Echocardiography was performed at the time of PET and 5–12 months after the CABG, and the wall motion recovery was evaluated on segmental and global bases. Consistency between PTF and 18F-FDG was evaluated visually and also in a quantitative manner. Predictive values for the wall motion recovery were also compared between the two approaches. Results The image quality of 18F-FDG was superior to that of 15O-water. The qualitative PTF showed significantly smaller defects than 18F-FDG, and the quantitative PTF showed slightly greater values than 18F-FDG in the infarcted region. The two methods were, however, consistent visually and also quantitatively. The predictive values of the wall motion recovery were almost equal between the two approaches. The absolute 18F-FDG uptake was varied in normal segments, and predictive values for the wall motion recovery by the absolute 18F-FDG was less (accuracy: 80 %) compared with those by the relative 18F-FDG (accuracy: 87 %) and the quantitative PTF (accuracy: 89 %). Conclusion Despite the small sample size, PTF appears to give consistent results with the 18F-FDG approach, and might be an alternative viability assessment.

Background Patient movement has been considered an important source of errors in cardiac PET. This study was aimed at evaluating the effects of such movement on myocardial blood flow (MBF) and perfusable tissue fraction (PTF) measurements in intravenous 15O-water PET. Methods Nineteen 15O-water scans were performed on ten healthy volunteers and three patients with severe cardiac dysfunction under resting conditions. Motions of subjects during scans were estimated by monitoring locations of markers on their chests using an optical motion-tracking device. Each sinogram of the dynamic emission frames was corrected for subject motion. Variation of regional MBF and PTF with and without the motion corrections was evaluated. Results In nine scans, motions during 15O-water scan (inter-frame (IF) motion) and misalignments relative to the transmission scan (inter-scan (IS) motion) larger than the spatial resolution of the PET scanner (4.0 mm) were both detected by the optical motion-tracking device. After correction for IF motions, MBF values changed from 0.845 ± 0.366 to 0.780 ± 0.360 mL/minute/g (P

In a typical single photon emission computed tomography (SPECT) system, intrinsic spatial resolution depends on the accuracy of the identification of an interacting point, which is dominated by propagation of the scintillation photons in the detector block. This study was intended to establish a Monte Carlo simulation-based evaluation tool taking into account the propagation of scintillation photons to estimate the intrinsic spatial and energy resolutions of the position-sensitive scintillator block in a SPECT detector.We employed Geant4 Monte Carlo simulation library which incorporated the optical photon processes for two different designs of the position-sensitive scintillator blocks. The validation of the simulation code was performed for a monolithic NaI(Tl) scintillator (251 × 147 × 6.4 mm(3)) coupled to 15 flat-panel type multi-anode photo multiplier tubes (PMT) (H8500: Hamamatsu) and results were compared with those obtained experimentally. The code was then applied to a LaBr(3)(Ce) scintillator of 120 mm square with varied thicknesses for designing high-resolution detector.The simulation resulted in 2.6 mm full width at half maximum (FWHM) of spatial resolution and 9.0% FWHM of energy resolution for the NaI(Tl)-based detector, which were in a good agreement of the experimental results, i.e., 2.7 mm and 10%, respectively. These findings suggest that Geant4 simulation including optical photon processes enables to predict the spatial and energy resolutions of a SPECT detector block accurately. The simulation also demonstrated that 2 mm spatial resolution can be obtained for a 6 mm thickness of the LaBr(3)(Ce), which is a significant improvement in performance as compared to existing gamma camera system that employs the scintillation detector fitted with PMTs.The Monte Carlo simulation-based evaluation tool was established to estimate the intrinsic spatial and energy resolutions of SPECT detector with position sensitive PMTs. This simulation may be useful to provide an optimal design of a SPECT detector without physical experiments.

The authors report a rare case of slowly progressive neuronal death associated with postischemic hyperperfusion in cortical laminar necrosis after radial artery/external carotid artery–middle cerebral artery bypass graft surgery for an intracavernous carotid artery aneurysm. Under barbiturate protection, a 69-year-old man underwent high-flow bypass surgery combined with carotid artery sacrifice for a symptomatic intracavernous aneurysm. The patient became restless postoperatively, and this restlessness peaked on postoperative Day (POD) 7. Diffusion-weighted and FLAIR MR images obtained on PODs 1 and 7 revealed subtle cortical hyperintensity in the temporal cortex subjected to temporary occlusion. On POD 13, 123I-iomazenil (123I-IMZ) SPECT clearly showed increased distribution on the early image and mildly decreased binding on the delayed image with count ratios of the affected–unaffected corresponding regions of interest of 1.23 and 0.84, respectively, suggesting postischemic hyperperfusion. This was consistent with the finding on 123I-iodoamphetamine SPECT. Of note, neuronal density in the affected cortex on the delayed 123I-IMZ image further decreased to the affected/unaffected ratio of 0.44 on POD 55 during the subacute stage when characteristic cortical hyperintensity on T1-weighted MR imaging, typical of cortical laminar necrosis, was emerging. The affected cortex showed marked atrophy 8 months after the operation despite complete neurological recovery. This report illustrates, for the first time, dynamic neuroradiological correlations between slowly progressive neuronal death shown by 123I-IMZ SPECT and cortical laminar necrosis on MR imaging in human stroke.

Cardiac (15)O-water PET studies provide an accurate quantitation of regional myocardial blood flow (rMBF). We developed a motion correction system using an optical motion-tracking device to detect a subject's global movement for cardiac study.PET studies were carried out on a cardiac phantom and a healthy volunteer at rest. The three-dimensional locations of the markers attached to the subjects during scans were measured using an optical motion-tracking system. In the phantom study, we performed a transmission scan and seven (18)F emission scans of a baseline and with artificial misalignment of shifts and rotations. The correlation coefficients between the baseline and the other images before and after the corrections for the misalignment were calculated. In the human study, we performed a (15)O-water dynamic scan with a transmission and axially 30 mm-shifted transmission scans. Motion of the subject was estimated by the information from the system, and was corrected on each sinogram using attenuation maps realigned to dynamic frames. Reconstructed dynamic images were then realigned to the transmission data. We calculated rMBF values for nine segments and myocardial images from the emission images, which were reconstructed with the first attenuation map (reference) and with the misaligned attenuation map before and after our corrections.In the phantom study, the correlation coefficients were improved from 0.929 +/- 0.022 to 0.987 +/- 0.010 (mean +/- SD) after the corrections. In the human study, the global and cyclic movements were detected. The cyclic movement due to respiration was smoothed by frame-averaging, and reasonable information of the global movement was obtained. The rMBF value (mean +/- SD) was 0.94 +/- 0.12 mL/min/g for the reference. The rMBF values using the misaligned attenuation map changed from 1.03 +/- 0.21 to 0.93 +/- 0.11 mL/min/g after the correction, and spurious defects in myocardial images were also recovered.Our technique provided reasonable information for correcting the global movement of the subject. It was shown that this system was applicable to detect and correct subject movement in cardiac PET studies at rest.

Cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO(2)), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) are quantitatively measured with PET with (15)O gases. Kudomi et al. developed a dual tracer autoradiographic (DARG) protocol that enables the duration of a PET study to be shortened by sequentially administrating (15)O(2) and C(15)O(2) gases. In this protocol, before the sequential PET scan with (15)O(2) and C(15)O(2) gases ((15)O(2)-C(15)O(2) PET scan), a PET scan with C(15)O should be preceded to obtain CBV image. C(15)O has a high affinity for red blood cells and a very slow washout rate, and residual radioactivity from C(15)O might exist during a (15)O(2)-C(15)O(2) PET scan. As the current DARG method assumes no residual C(15)O radioactivity before scanning, we performed computer simulations to evaluate the influence of the residual C(15)O radioactivity on the accuracy of measured CBF and OEF values with DARG method and also proposed a subtraction technique to minimize the error due to the residual C(15)O radioactivity.In the simulation, normal and ischemic conditions were considered. The (15)O(2) and C(15)O(2) PET count curves with the residual C(15)O PET counts were generated by the arterial input function with the residual C(15)O radioactivity. The amounts of residual C(15)O radioactivity were varied by changing the interval between the C(15)O PET scan and (15)O(2)-C(15)O(2) PET scan, and the absolute inhaled radioactivity of the C(15)O gas. Using the simulated input functions and the PET counts, the CBF and OEF were computed by the DARG method. Furthermore, we evaluated a subtraction method that subtracts the influence of the C(15)O gas in the input function and PET counts.Our simulations revealed that the CBF and OEF values were underestimated by the residual C(15)O radioactivity. The magnitude of this underestimation depended on the amount of C(15)O radioactivity and the physiological conditions. This underestimation was corrected by the subtraction method.This study showed the influence of C(15)O radioactivity in DARG protocol, and the magnitude of the influence was affected by several factors, such as the radioactivity of C(15)O, and the physiological condition.

Purpose Quantitative estimates of dopamine transporter availability, determined with [123I]FP-CIT SPECT, depend on the SPECT equipment, including both hardware and (reconstruction) software, which limits their use in multicentre research and clinical routine. This study tested a dedicated reconstruction algorithm for its ability to reduce camera-specific intersubject variability in [123I]FP-CIT SPECT. The secondary aim was to evaluate binding in whole brain (excluding striatum) as a reference for quantitative analysis. Methods Of 73 healthy subjects from the European Normal Control Database of [123I]FP-CIT recruited at six centres, 70 aged between 20 and 82 years were included. SPECT images were reconstructed using the QSPECT software package which provides fully automated detection of the outer contour of the head, camera-specific correction for scatter and septal penetration by transmission-dependent convolution subtraction, iterative OSEMreconstruction including attenuation correction, and camera-specific Bto kBq/ml^ calibration. LINK and HERMES reconstruction were used for head-to-head comparison. The specific striatal [123I]FP-CIT binding ratio (SBR) was computed using the Southampton method with binding in the whole brain, occipital cortex or cerebellum as the reference. The correlation between SBR and age was used as the primary quality measure. Results The fraction of SBR variability explained by age was highest (1) with QSPECT, independently of the reference region, and (2) with whole brain as the reference, independently of the reconstruction algorithm. Conclusion QSPECT reconstruction appears to be useful for reduction of camera-specific intersubject variability of [123I]FP-CIT SPECT in multisite and single-site multicamera settings. Whole brain excluding striatal binding as the reference provides more stable quantitative estimates than occipital or cerebellar binding.

Background and Purposes— Recent clinical evidences indicate that statins may have beneficial effects on the functional recovery after ischemic stroke. However, the effect of delayed postischemic treatment with statins is still unclear. In the present study, we evaluated the effects of fluvastatin in the chronic stage of cerebral infarction in a rat model. Methods— Rats exposed to permanent middle cerebral artery occlusion were treated for 3 months with fluvastatin beginning from 7 days after stroke. MRI, behavioral analysis, and immunohistochemistry were performed. Results— Two months of treatment with fluvastatin showed the significant recovery in spatial learning without the decrease in serum total cholesterol level and worsening of infarction. Microangiography showed a significant increase in capillary density in the peri-infarct region in fluvastatin-treated rats after 3 months of treatment. Consistently, BrdU/CD31-positive cells were significantly increased in fluvastatin-treated rats after 7 days of treatment. MAP1B-positive neurites were also increased in the peri-infarct region in fluvastatin-treated rats. In addition, rats treated with fluvastatin showed the reduction of superoxide anion after 7 days of treatment and the reduction of Aβ deposits in the thalamic nuclei after 3 months of treatment. Conclusions— Thus, delayed postischemic administration of fluvastatin had beneficial effects on the recovery of cognitive function without affecting the infarction size after ischemic stroke. Pleiotropic effects of fluvastatin, such as angiogenesis, neuritogenesis, and inhibition of superoxide production and Aβ deposition, might be associated with a favorable outcome.

Background The resolution of a gamma camera is depth-dependent and worsens with increasing distance to the camera resulting in a loss of fine details in SPECT images. A common approach to reduce the effects of this resolution loss is to utilize body-contour acquisition orbits. Even though body-contour orbits can improve resolution of reconstructed images their effect on lesion detection is not well known. Objective To investigate whether body-contour orbits offer better defect detection performance than circular orbits in cardiac SPECT. Methods The mathematical cardiac torso (MCAT) phantom was used to model 99mTc-sestamibi uptake. A total of four phantoms (two male and two female) with eight defects (four locations and two sizes) were generated and projection data were simulated using an analytical projector with attenuation, scatter, collimator response and acquisition orbit modelling. The circular and body-contour projections were reconstructed using the OSEM algorithm with/without collimator response compensation. Defect detection performance was assessed by calculating area under the receiver operating characteristic (ROC) curve for channelized Hotelling observer. Results The defect detection performance of circular and body-contour acquisition was very similar and the difference in the area under the ROC curve between the orbits was not statistically significant with or without collimator response compensation. The collimator response compensation, on the other hand, was noticed to be valuable and it provided significantly better defect detection performance than reconstruction without it regardless of the acquisition orbit type. Conclusions We conclude that by replacing circular orbit with more complex body-contour orbit will not lead to statistically significant increase in defect detection performance in cardiac SPECT.

OBJECTIVE It is difficult to distinguish between bipolar disorder and major depressive disorder (MDD) in patients lacking a clear history of mania. There is an urgent need for an objective biomarker for differential diagnosis. Using diffusion tensor imaging, this study investigated the differences in the brain white matter microstructure between patients with bipolar disorder and MDD. METHODS Participants included 16 patients with bipolar disorder and 23 patients with MDD having depressed or euthymic states based on DSM-IV-TR criteria and 23 healthy volunteers. Whole-brain voxel-based morphometric analysis was used to detect any significant differences in fractional anisotropy between patients with bipolar disorder and MDD. The study was conducted between August 2011 and July 2015. RESULTS We found a significant decrease in fractional anisotropy values in the anterior part of the corpus callosum in patients with bipolar disorder compared with MDD (P < .001), which did not depend on the patients' affective state. This decrease was associated with increased radial diffusivity values (P < .05), which was also found in patients with bipolar disorder when compared with healthy volunteers (P < .05). We predicted bipolar disorder and MDD in all patients using the fractional anisotropy values, with a correct classification rate of 76.9%. CONCLUSIONS The present study revealed that patients with bipolar disorder have microstructural abnormalities in the corpus callosum during depressed or euthymic states, which may deteriorate the exchange of emotional information between the cerebral hemispheres, resulting in emotional dysregulation. Our results indicate the possible use of diffusion tensor imaging as a differential diagnostic tool.

A new method has been developed for diffusible tracers, to quantify CBF at rest and after pharmacological stress from a single session of dynamic scans with dual bolus administration of a radiotracer. The calculation process consisted of three steps, including the procedures of incorporating background radioactivity contaminated from the previous scan. Feasibility of this approach was tested on clinical SPECT studies on 16 subjects. Two sequential SPECT scans, 30 min apart, were carried out on each subject, after each of two split-dose administrations of 111 MBq IMP. Of these, 11 subjects received acetazolamide at 10 min before the second IMP injection. Additional PET scans were also carried out on 6 subjects on a separate day, at rest and after acetazolamide administration. The other 5 subjects were scanned only at rest during the whole study period. Quantitative CBF obtained by this method was in a good agreement with those determined with PET (y(ml/100 g/min) = 1.07 × (ml/100 g/min) − 1.14, r = 0.94). Vasareactivity was approximately 40% over the whole cerebral area on healthy controls, which was consistent with a literature value. Reproducibility of CBF determined in the rest–rest study was 1.5 ± 5.7%. Noise enhancement of CBF images, particularly the second CBF, was reduced, providing reasonable image quality. Repeat assessment of quantitative CBF from a single session of scans with split-dose IMP is accurate, and may be applied to clinical research for assessing vascular reactivity in patients with chronic cerebral vascular disease.

BACKGROUND AND OBJECTIVES: Statistical reconstruction methods allow resolution recovery in tomographic reconstruction. Even though resolution recovery has the potential to improve overall image quality, pinhole SPECT images are still often reconstructed using simplified models of the acquisition geometry in order to reduce reconstruction time. This paper investigates the benefits of two resolution recovery methods, multi-ray and point-spread function based, in pinhole SPECT by comparing them to uncorrected reconstruction. METHODS: Resolution recovery was incorporated into ordered subsets expectation maximization reconstruction algorithm. The first of the correction methods used a simple but very fast multiple projection ray approach, whereas the second, much slower, method modelled the acquisition geometry more accurately using the analytical point-spread function of the pinhole collimator. Line source, Jaszczak and contrast phantom studies were performed and used for comparison. RESULTS: Resolution recovery improved resolution, contrast and visual quality of the images when compared to reconstructions without it. The method based on the point-spread function performed slightly better, but was almost 50 times slower than the much simpler multi-ray approach. CONCLUSION: The multiple projection ray approach is a promising method for very fast and easy resolution recovery in pinhole SPECT. It has a profound effect on image quality and can markedly improve the resolution-sensitivity trade-off.

There is no specific treatment to improve the functional recovery in the chronic stage of ischemic stroke. To provide the new therapeutic options, we examined the effect of overexpression of hepatocyte growth factor (HGF) in the chronic stage of cerebral infarction by transferring the HGF gene into the brain using hemagglutinating virus of Japan envelope vector. Sixty rats were exposed to permanent middle cerebral artery occlusion (day 1). Based on the sensorimotor deficits at day 7, the rats were divided equally into control vector or HGF-treated rats. At day 56, rats transfected with the HGF gene showed a significant recovery of learning and memory in Morris water maze tests (control vector 50±4 s; HGF 33±5 s; P P

Objective Nicotinic acetylcholine receptors have close interactions with the dopaminergic system and play critical roles in cognitive function. The purpose of this study was to compare these receptors between living PD patients and healthy subjects. Methods Nicotinic acetylcholine receptors were imaged in 10 nondemented Parkinson's disease patients and 15 age-matched healthy subjects using a single-photon emission computed tomography ligand [123I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine. Using an arterial input function, we measured the total distribution volume (V; specific plus nondisplaceable), as well as the delivery (K1). Results Parkinson's disease showed a widespread significant decrease (approximately 10%) of V in both cortical and subcortical regions without a significant change in K1. Interpretation These results indicate the importance of extending the study to demented patients. Ann Neurol 2006;59:174–177

Prior studies with anthropomorphic phantoms and single, static in vivo brain images have demonstrated that scatter correction significantly improves the accuracy of regional quantitation of single-photon emission tomography (SPET) brain images. Since the regional distribution of activity changes following a bolus injection of a typical neuroreceptor ligand, we examined the effect of scatter correction on the compartmental modeling of serial dynamic images of striatal and extrastriatal dopamine D(2) receptors using [(123)I]epidepride. Eight healthy human subjects [age 30+/-8 (range 22-46) years] participated in a study with a bolus injection of 373+/-12 (354-389) MBq [(123)I]epidepride and data acquisition over a period of 14 h. A transmission scan was obtained in each study for attenuation and scatter correction. Distribution volumes were calculated by means of compartmental nonlinear least-squares analysis using metabolite-corrected arterial input function and brain data processed with scatter correction using narrow-beam geometry micro (SC) and without scatter correction using broad-beam micro (NoSC). Effects of SC were markedly different among brain regions. SC increased activities in the putamen and thalamus after 1-1.5 h while it decreased activity during the entire experiment in the temporal cortex and cerebellum. Compared with NoSC, SC significantly increased specific distribution volume in the putamen (58%, P=0.0001) and thalamus (23%, P=0.0297). Compared with NoSC, SC made regional distribution of the specific distribution volume closer to that of [(18)F]fallypride. It is concluded that SC is required for accurate quantification of distribution volumes of receptor ligands in SPET studies.

Flow quantitation with nitrogen-13 ammonia ((13)NH(3)) and positron emission tomography (PET) is dependent on an accurate blood time-activity curve. This is conveniently derived from the PET images by drawing a region of interest in the left ventricular cavity. The blood time-activity curve obtained in this way, however, may contain spillover from the myocardial wall. The purpose of this study was to analyse the effect of wall to blood pool spillover. Additionally, we analysed the application of a left atrial input function. Using computer simulations, we investigated the effect of spillover from the myocardial wall to the left ventricular input function and the effect of time delay on the left ventricular input function. An oxygen-15 carbon monoxide PET study of seven normal volunteers was used to investigate possible recovery issues regarding the left atrial input function. Finally, (13)NH(3) studies of 31 normal volunteers during rest and dipyridamole stimulation were analysed using either a left atrial or a left ventricular input function. The simulation studies showed that myocardial wall to blood pool spillover causes a considerable underestimation of the regional blood flow values in hyperaemic flow studies. Neither time delay nor recovery issues prevent flow quantitation with a left atrial input function. The (13)NH(3) studies revealed no significant difference between the resting blood flow values, whereas the hyperaemic blood flow values were underestimated by 8% (P0.01) on average (up to 40% individually) when using a left ventricular input function compared with a left atrial input function. Spillover of activity from the left ventricular wall to the blood time-activity curve is of importance in hyperaemic flow studies using (13)NH(3). Application of a left atrial input function is a possible solution to these issues.

Repetitive transcranial magnetic stimulation (rTMS) recently has been assessed as a noninvasive treatment modality for movement and psychiatric disorders, whereas the mechanism underlying the therapeutic effects is not fully understood. Studies in rodents showed lasting functional changes in some selected regions, such as limbic-associated structures, but unfocused brain stimulation did not clarify the regional effects. To address the topographical and temporal profiles of the effects on glucose metabolism in primate brain, we performed rTMS and repeated (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) before, during, and up to 16 days after rTMS in anesthetized cynomologous monkeys. We delivered a total of 2,000 pulses of 5 Hz-rTMS over the right precentral gyrus using a small-sized eight-figured coil that induced a localized electrical field. Voxel-based analysis in a standard space of the macaque brain showed statistically robust changes in FDG uptake: a decrease in the motor/premotor cortices and an increase in the limbic-associated areas involving the anterior/posterior cingulate, and orbitofrontal cortices. Interestingly, these uptake changes continued for at least 8 days and the magnitude of the lasting effects in the limbic-related areas was negatively correlated across subjects with those in the motor/premotor cortices. The results demonstrate that motor rTMS has a long-term lasting effect on motor-related regions and distant limbic-related areas via functional connections.

When the relationship between ageing and changes in personality traits is considered, it is important to know how they are influenced by biological and environmental factors. The present study examined the relationships between various factors associated with the effect of ageing on personality traits, including structural changes of the brain and environmental factors such as education.We recruited 41 healthy subjects. We administered the NEO Five-Factor Inventory to assess personality factors. Magnetic resonance imaging was performed, and regional grey matter (GM) volumes were obtained. We identified associations in the correlation analysis of age, cerebral GM volume, years of education, and the personality trait of openness. Path analysis was used to estimate the relationships among these factors.The path analysis model of age, GM volume, years of education, and the personality trait of openness revealed that age has an indirect negative association with openness through GM volume and years of education. Ageing was related to a decrease in GM volume, which was in turn related to a decrease in the openness score. Older subjects generally had fewer years of education, which was related to a lower openness score.Maintaining openness against the effects of ageing is desirable, and our results imply that interventions against age-related cerebral atrophy and the promotion of opportunities for higher education may contribute to the development and stability of a healthy personality during the adult life course.

Several epidemiological studies have found a lower incidence of Alzheimer's disease in highly educated populations, but the protective mechanism of education against the disease is still unclear. Our objective was to investigate the association between education and (11) C-labeled Pittsburgh Compound B (PIB) uptake with positron emission tomography in participants with normal cognitive ability.We performed (11) C-labeled PIB positron emission tomography and neuropsychological testing in 30 cognitively normal older participants. Of the participants, 16 had a period of education less than 12 years (low-education group) and 14 had more than 13 years (high-education group). Amyloid-β deposition was quantified by binding potential (BPND ) in several brain regions and was compared between the groups with different education levels.We found significantly higher cortical PIB-BPND in the cognitively normal participants with low education compared with the ones with high education. None of the brain regions in low-education group showed significantly lower BPND values. This finding was not affected by the inclusion of possible confounding variables such as age, sex, and general intelligence. Our findings indicated a reduced amyloid pathology in highly educated, cognitively normal, participants.Our findings lead to the proposal that early-life education has a negative association with Alzheimer's disease pathology. This proposal is not in opposition to the brain reserve hypothesis. People with more education might be prone to a greater inhibitory effect against amyloid-β deposition before the preclinical stage. At the same time, they have a greater reserve capacity, and greater pathological changes are required for dementia to manifest.

A few studies have been performed on chronic structural changes after stroke. The primary purpose of the present study was to investigate regional cortical volume changes after the onset of stroke and to examine how the cortical volume changes affected neuropsychiatric symptoms.Participants were 20 stroke patients and 14 control subjects. T1-MRI was performed twice, once at the subacute stage and again 6 months later, and whole brain voxel-based morphometric (VBM) analysis was used to detect significant cortical gray matter volume changes in patients. We also assessed the correlation between changes in cortical volumes and changes in neuropsychiatric symptoms during the 6 months following a stroke.In the present study, we found significant volume reductions in the anterior part of the posterior cingulate cortex (PCC) over the 6 months following a stroke by exploratory VBM analysis. We also found that the amount of volume change was significantly correlated with the change in apathy-scale scores during the 6 months poststroke.The present study suggests that delayed atrophic change is evident in the PCC 6 months after a stroke. There was greater apathetic change in the stroke patients with the larger volume reductions. The delayed atrophy of the PCC may reflect degeneration secondary to neuronal loss due to stroke. Such degeneration might have impaired control of goal-directed behavior, leading to the observed increase in apathy.

Increased carotid artery wall thickness and lipoprotein oxidation are key early events in atherosclerosis. To test the hypothesis that reduced myocardial flow reserve is a marker of subclinical atherosclerosis, we examined the relationships between flow reserve and carotid artery intima-media thickness (IMT) in young men free from coronary heart disease. Basal and dipyridamole stimulated coronary blood flow was measured using positron emission tomography (PET) in 55 healthy men aged 36+/-4 years. Myocardial flow reserve was calculated as the ratio of stimulated flow to basal flow. The mean carotid artery IMT was measured using high-resolution ultrasound. Oxidised LDL was measured as baseline LDL diene conjugation. Myocardial flow reserve decreased across the quartiles of increasing IMT (P=0.006), and was 5.2+/-1.9 in the lowest quartile for IMT and 3.7+/-1.2 in the highest (P=0.04, I vs. IV quartile). In univariate analysis, oxidised LDL correlated inversely with flow reserve (r=-0.35, P=0.01) and directly with IMT (r=0.51, P

PURPOSE The aim of this study was to investigate the clinical value of coregistration of interictal SPECT and magnetic resonance imaging (MRI) in patients with partial epilepsy. MATERIALS AND METHODS Seventeen patients with partial epilepsy were examined with I-123 IMP or Tc-99m ethyl cysteinate dimer SPECT during the interictal phase. The SPECT images were automatically coregistered to axial T1 weighted MRIs. Asymmetry indexes (AIs) were calculated in both nonregistered images and coregistered images. RESULTS SPECT images showed areas of decreased tracer uptake in 12 patients. In two patients, the relation between the tumor and the extent of decreased uptake became more accurate in the coregistered images. In five cases, the coregistered images clearly showed that the decreased uptake was located in the sulcus. The AIs were significantly reduced from 14.29 +/- 7.23 to 5.86 +/- 3.48 (P < 0.001) after the images were coregistered in these cases. In five cases, the coregistered images indicated that the decreased areas were in agreement with the cortical findings. No significant differences in the AIs were observed in these cases (16.50 +/- 6.19 versus 17.83 +/- 4.45). Thus, the coregistered images were useful not only to differentiate actual hypoperfusion from artificial hypoperfusion resulting from partial volume effects but also to improve the accuracy of AIs. CONCLUSION The coregistration of interictal perfusion SPECT and MRI is useful not only to provide precise functional and anatomic mapping but also to improve the accuracy of calculations of the semiquantitative analysis of regional cerebral blood flow parameters during the interictal state of epilepsy.

Aims Levosimendan, a novel calcium-dependent calcium sensitizer of the myocardial contractile proteins, also enhances diastolic relaxation and induces peripheral vasodilation by opening potassium channels. To assess the combined energetical effects of levosimendan infusion in vivo, we performed positron emission tomography in patients with decompensated chronic heart failure. Methods And Results Eight hospitalized patients with New York Heart Association functional class III or IV heart failure received levosimendan or placebo intravenously in a randomized double-blind cross-over study. During steady-state, dynamic positron emission tomography with [11C]acetate was used to assess myocardial oxygen consumption and [15O]H2O to measure myocardial blood flow. Cardiac performance and dimensions were assessed by pulmonary artery catheterization and echocardiography. Compared with healthy volunteers, myocardial oxygen consumption during placebo was elevated in the right ventricle but comparable in the left ventricle. During administration of levosimendan, cardiac output increased by 32% (P = .002) mainly because of higher stroke volume. Coronary, pulmonary, and systemic vascular resistance values were significantly reduced. Mean myocardial blood flow increased from 0.76 to 1.02 mL/min/g (P = .033). Levosimendan was neutral on myocardial oxygen consumption and left ventricular efficiency, but it improved right ventricular mechanical efficiency by 24% (P = .012). Conclusions Levosimendan has an energetically favorable short-term profile in the treatment of congestive heart failure. It enhances cardiac output without oxygen wasting, particularly by improving efficiency in the right ventricle. Clinical Pharmacology & Therapeutics (2000) 68, 522–531; doi: 10.1067/mcp.2000.110972

One of the most limiting factors for the accurate quantification of physiologic parameters with positron emission tomography (PET) is the partial volume effect (PVE). To assess the magnitude of this contribution to the measurement of regional cerebral blood flow (rCBF), the authors have formulated four kinetic models each including a parameter defining the perfusable tissue fraction (PTF). The four kinetic models used were 2 one-tissue compartment models with (Model A) and without (Model B) a vascular term and 2 two-tissue compartment models with fixed (Model C) or variable (Model D) white matter flow. Furthermore, rCBF based on the autoradiographic method was measured. The goals of the study were to determine the following in normal humans: (1) the optimal model, (2) the optimal length of fit, (3) the model parameters and their reproducibility, and (4) the effects of data acquisition (2D or 3D). Furthermore, the authors wanted to measure the activation response in the occipital gray matter compartment, and in doing so test the stability of the PTF, during perturbations of rCBF induced by visual stimulation. Eight dynamic PET scans were acquired per subject (n = 8), each for a duration of 6 minutes after IV bolus injection of H215O. Four of these scans were performed using 2D and four using 3D acquisition. Visual stimulation was presented in four scans, and four scans were during rest. Model C was found optimal based on Akaike's Information Criteria (AIC) and had the smallest coefficient of variance after a 6-minute length of fit. Using this model the average PVE corrected rCBF during rest in gray matter was 1.07 mL·min−1·g−1 (0.11 SD), with an average coefficient of variance of 6%. Acquisition mode did not affect the estimated parameters, with the exception of a significant increase in the white matter rCBF using the autoradiographic method (2D: 0.17 mL·min−1·g−1 (0.02 SD); 3D: 0.21 mL·min−1·g−1 (0.02 SD)). At a 6-minute fit the average gray matter CBF using Models C and D were increased by 100% to 150% compared with Models A and B and the autoradiographic method. There were no significant changes in the perfusable tissue fraction by the activation induced rCBF increases. The largest activation response was found using Model C (median = 39.1%). The current study clearly demonstrates the importance of PVE correction in the quantitation of rCBF in normal humans. The potential use of this method is to cost-effectively deliver PVE corrected measures of rCBF and tissue volumes without reference to imaging modalities other than PET.

The transmission dependent convolution subtraction method which is one of the methods for scatter correction of SPECT was applied to the assessment of CBF using SPECT and I-123-IMP. The effects of scatter correction on regional distribution of CBF were evaluated on a pixel by pixel basis by means of an anatomic standardization technique. SPECT scan was performed on six healthy men. Image reconstruction was carried out with and without the scatter correction. All reconstructed images were globally normalized for the radioactivity of each pixel, and transformed into a standard brain anatomy. After anatomic standardization, the average SPECT images were calculated for scatter corrected and uncorrected groups, and these groups were compared on pixel by pixel basis. In the scatter uncorrected group, a significant overestimation of CBF was observed in the deep cerebral white matter, pons, thalamus, putamen, hippocampal region and cingulate gyrus as compared with scatter corrected group. A significant underestimation was observed in all neocortical regions, especially in the occipital and parietal lobes, and the cerebellar cortex. The regional distribution of CBF obtained by scatter corrected SPECT was similar to that obtained by O-15 water PET. The scatter correction is needed for the assessment of CBF using SPECT.

Background and Purpose —Dipyridamole increases the concentration of circulating adenosine, which is a potent vasodilator, by inhibition of uptake of adenosine into the erythrocytes, and hence produces coronary vasodilation. However, the effects of dipyridamole on cerebral circulation is not pronounced. This study investigates the effects of intravenous dipyridamole on cerebral blood flow (CBF) in humans with use of positron emission tomography (PET). Methods —In each of 13 healthy subjects, CBF was measured using 15 O-labeled water and PET at rest and during hypercapnia, hypocapnia, and dipyridamole stress; corresponding CBF values were then compared. Results —CBF values during dipyridamole stress were significantly lower than those measured at rest. The dipyridamole stress Pa co 2 was also significantly lower than the resting Pa co 2 . The change in CBF during dipyridamole stress relative to Pa co 2 closely followed the relationship between CBF and Pa co 2 during hypocapnia. Conclusions —These results indicate that the observed decrease in CBF during dipyridamole stress was caused by a decrease in Pa co 2 rather than by any direct action of dipyridamole on CBF. The decrease in Pa co 2 during dipyridamole stress was most likely due to hyperventilation, which was a side effect of adenosine. These results support the hypothesis that circulating adenosine is largely prevented from binding to adenosine receptors of cerebral vessels by the blood-brain barrier.

OBJECTIVE To determine whether insulin-stimulated blood flow in patients with mild essential hypertension is altered. SUBJECTS Eleven untreated mildly hypertensive patients [aged 35 +/- 2 years, body mass index 25.1 +/- 0.4 kg/m2, mean arterial pressure 110 +/- 2 mmHg (means +/- SEM) and 10 matched normotensive subjects (mean arterial pressure 94 +/- 3 mmHg). METHODS Blood flow was quantitated directly in skeletal muscle both basally and during supraphysiologic hyperinsulinemia (serum insulin approximately = 450 mU/l) using radiowater ([15O]H2O) and positron emission tomography. Whole-body and femoral muscle glucose uptakes were determined using the euglycemic insulin clamp technique, [18F]-2-fluoro-2-deoxy-D-glucose and positron emission tomography. RESULTS Rates of whole-body and femoral muscle glucose uptake were significantly lower in the hypertensive than in the normotensive group. Insulin increased muscle blood flow by 91% in the normotensive group, but only by 33% in the hypertensive group. CONCLUSIONS The ability of insulin to stimulate blood flow in patients with mild essential hypertension is impaired.

PLoS one 9(4), e95250 (2014). doi:10.1371/journal.pone.0095250, Published by PLoS [u.a.], Lawrence, Kan.