Search

Background and Purpose Carotid artery stenosis or occlusion (CASO) is a causative disease of vascular cognitive impairment (VCI) attributed to cerebral hypoperfusion, even without the development of symptomatic ischemic stroke. Preclinically, resveratrol has been demonstrated to play an important role in improving cognitive function in rodent CASO models. This study investigated the association between long-term resveratrol intake and improvements in cognitive and cerebral hemodynamic impairments in patients with CASO. Methods A retrospective cohort study was conducted on patients with asymptomatic carotid artery stenosis of ≥50% or occlusion who underwent 15O-gas positron emission tomography (15O-gas PET) and neuropsychological tests such as Montreal Cognitive Assessment (MoCA) and Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog) twice between July 2020 and March 2022 allowing >125-day interval. Patients were administered 30 mg/day resveratrol after the first 15O-gas PET and neuropsychological tests were compared with those who were not. Results A total of 79 patients were enrolled in this study; 36 received resveratrol and 43 did not. Over a mean follow-up of 221.2 and 244.8 days, long-term resveratrol treatment significantly improved visuospatial/executive function (P=0.020) in MoCA, and memory domain (P=0.007) and total score (P=0.019) in ADAS-Cog. Cerebral blood flow demonstrated improvement in the right frontal lobe (P=0.027), left lenticular nucleus (P=0.009), right thalamus (P=0.035), and left thalamus (P=0.010) on 15O-gas PET. No adverse events were reported. Conclusion Long-term daily intake of oral resveratrol may prevent or treat VCI by improving the cerebral blood flow in asymptomatic patients with CASO.

BackgroundCarotid artery stenosis or occlusion (CASO) is a major cause of vascular cognitive impairment (VCI). There is currently no effective treatment for VCI induced by CASO. Resveratrol, a type of polyphenol, improves cognitive performance in rat CASO models via pleiotropic effects. Furthermore, we previously reported the longevity gene, SIRT1, which can be activated by resveratrol, improves cognitive and cerebral blood flow impairment in mouse CASO models by activating endothelial nitric oxide synthase. However, clinical evidence remains limited.MethodsThe REsveratrol for VAscular cognitive impairment investigating cerebral Metabolism and Perfusion (REVAMP) trial is a randomized, double-blind, placebo-controlled trial involving patients with asymptomatic CASO. Each participant will receive either 150 mg/day of resveratrol or a placebo for 35 weeks. The primary objective is to determine whether resveratrol improves cognitive impairment, as assessed using the Alzheimer’s disease Assessment Scale–cognitive subscale 13. One of our secondary objectives is to determine whether resveratrol improves cerebral hemodynamic impairment as assessed via 15O-gas positron emission tomography. We will recruit 100 patients (50 per group).DiscussionThe REVAMP trial may provide valuable insights into new therapeutic options, as multitarget neuroprotection could potentially improve cognitive function along with enhancements in cerebral hemodynamic status in patients with asymptomatic CASO.Clinical trial registration: The REVAMP trial was prospectively registered in the Japan Registry of Clinical Trials (jRCTs051230013) on April 13, 2023.

Abstract Background Despite 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. Methods Renal 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 [15 O]H2O PET. Perfusion and Doppler resistance index (RI) of transplants were compared with histology of one-year protocol transplant biopsy. Results Renal cortical perfusion of healthy control subjects and transplant patients were 2.7 (2.4–4.0) ml min− 1 g− 1 and 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− 1 and 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 [15 O]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.

In this review, we will summarize the past and current state-of-the-art developments in attenuation and scatter correction approaches for hybrid positron emission tomography (PET) and magnetic resonance (MR) imaging. The current status of the methodological advances for producing accurate attenuation and scatter corrections on PET/MR systems are described, in addition to emerging clinical and research applications. Future prospects and potential applications that benefit from accurate data corrections to improve the quantitative accuracy and clinical applicability of PET/MR are also discussed. Novel clinical and research applications where improved attenuation and scatter correction methods are beneficial are highlighted.

Abstract Background 15O-oxygen inhalation PET is unique in its ability to provide fundamental information regarding cerebral hemodynamics and energy metabolism in man. However, the use of 15O-oxygen has been limited in a clinical environment largely attributed to logistical complexity, in relation to a long study period, and the need to produce and inhale three sets of radiopharmaceuticals. Despite the recent works that enabled shortening of the PET examination period, radiopharmaceutical production has still been a limiting factor. This study was aimed to evaluate a recently developed radiosynthesis/inhalation system that automatically supplies a series of 15O-labeled gaseous radiopharmaceuticals of C15O, 15O2, and C15O2 at short intervals. Methods The system consists of a radiosynthesizer which produces C15O, 15O2, and C15O2; an inhalation controller; and an inhalation/scavenging unit. All three parts are controlled by a common sequencer, enabling automated production and inhalation at intervals less than 4.5 min. The gas inhalation/scavenging unit controls to sequentially supply of qualified radiopharmaceuticals at given radioactivity for given periods at given intervals. The unit also scavenges effectively the non-inhaled radioactive gases. Performance and reproducibility are evaluated. Results Using an 15O-dedicated cyclotron with deuteron of 3.5 MeV at 40 μA, C15O, 15O2, and C15O2 were sequentially produced at a constant rate of 1400, 2400, and 2000 MBq/min, respectively. Each of radiopharmaceuticals were stably inhaled at

Abstract Background Microvascular function plays an important role in ARVD (atherosclerotic renovascular disease). RFR (renal flow reserve), the capacity of renal vasculature to dilate, is known to reflect renal microvascular function. In this pilot study, we assessed PET (positron emission tomography)-based RFR values of healthy persons and renal artery stenosis patients. Seventeen patients with ARVD and eight healthy subjects were included in the study. Intravenous enalapril 1 mg was used as a vasodilatant, and the maximum response (blood pressure and RFR) to it was measured at 40 min. Renal perfusion was measured by means of oxygen-15-labeled water PET. RFR was calculated as a difference of stress flow and basal flow and was expressed as percent [(stress blood flow − basal blood flow)/basal blood flow] × 100%. Results RFR of the healthy was 22%. RFR of the stenosed kidneys of bilateral stenosis patients (27%) was higher than that of the stenosed kidneys of unilateral stenosis patients (15%). RFR of the contralateral kidneys of unilateral stenosis patients was 21%. There was no difference of statistical significance between RFR values of ARVD subgroups or between ARVD subgroups and the healthy. In the stenosed kidneys of unilateral ARVD patients, stenosis grade of the renal artery correlated negatively with basal (p = 0.04) and stress flow (p = 0.02). Dispersion of RFR values was high. Conclusions This study is the first to report [15O]H2O PET-based RFR values of healthy subjects and ARVD patients in humans. The difference between RFR values of ARVD patients and the healthy did not reach statistical significance perhaps because of high dispersion of RFR values. [15O]H2O PET is a valuable non-invasive and quantitative method to evaluate renal blood flow though high dispersion makes imaging challenging. Larger studies are needed to get more information about [15O]H2O PET method in evaluation of renal blood flow.

Abstract 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.

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.

Background A significantly lower fractional anisotropy (FA) value has been shown in anterior parts of the corpus callosum in patients with bipolar disorder. Aims We investigated the association between abnormal corpus callosum integrity and interhemispheric functional connectivity (IFC) in patients with bipolar disorder. Methods We examined the association between FA values in the corpus callosum (CC-FA) and the IFC between homotopic regions in the anterior cortical structures of bipolar disorder (n=16) and major depressive disorder (n=22) patients with depressed or euthymic states. Results We found a positive correlation between the CC-FA and IFC values between homotopic regions of the ventral prefrontal cortex and insula cortex, and significantly lower IFC between these regions in bipolar disorder patients. Conclusions The abnormal corpus callosum integrity in bipolar disorder patients is relevant to the IFC between homotopic regions, possibly disturbing the exchange of emotional information between the cerebral hemispheres resulting in emotional dysregulation.

Background: The objective of this study was to examine the relationship between the myelination and the psychological trait of openness to experience in young cognitively normal volunteers using regional T1-weighted (T1w)/T2w ratios on magnetic resonance imaging (MRI). It was hypothesized that axonal myelination would be related to openness, thus linking trait creativity and mental illness. Methods: We recruited 37 healthy subjects and administered the NEO Five-Factor Inventory to assess personality factors. Regional T1w/T2w MRI values were computed as surrogate indicators of myelination status and correlations between T1w/T2w values and various personality factors (e.g., trait of openness) were calculated with a voxel-based analysis using statistical parametric mapping. Results: Significant negative correlations were identified between the trait of openness and T1w/T2w values in the medial frontal cortex, anterior cingulate cortex, posterior cingulate cortex, and posterior insula/adjacent putamen. These relationships remained significant even after adjusting for age, sex, and education as covariates. There were no significant correlations between other personality factors and regional volumes. Conclusions: Individual differences in openness may be associated with variations in intra-cortical myelination, specifically in the imaginative network of the brain including the midline core ‘hubs’ of the default mode network (anterior cingulate/medial frontal cortex and posterior cingulate cortex) and regions related to motivational state (posterior insula and adjacent putamen). Signal interference related to decreased myelination may facilitate flexible imagination and the trait of openness. Our findings assist in understanding the relationship between myelination and openness, as a link between creativity and mental illness.

BackgroundExisting 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 ResultsAdult 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. ConclusionsThe 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.

Simultaneous, hybrid MR-PET is expected to improve PET image resolution in the plane perpendicular to the static magnetic field of the scanner. Previous papers have reported this either by simulation or experiment with simple sources and detector arrangements. Here, we extend those studies using a realistic brain phantom in a recently installed MR-PET system comprising a 9.4 T MRI-scanner and an APD-based BrainPET insert in the magnet bore. Point and line sources and a 3D brain phantom were filled with 18F (low-energy positron emitter), 68Ga (medium energy positron emitter) or 120I, a non-standard positron emitter (high positron energies of up to 4.6 MeV). Using the BrainPET insert, emission scans of the phantoms were recorded at different positions inside and outside the magnet bore such that the magnetic field was 0 T, 3 T, 7 T or 9.4 T. Brain phantom images, with the 'grey matter' compartment filled with 18F, showed no obvious resolution improvement with increasing field. This is confirmed by practically unchanged transaxial FWHM and 'grey/white matter' ratio values between at 0T and 9.4T. Field-dependent improvements in the resolution and contrast of transaxial PET images were clearly evident when the brain phantom was filled with 68Ga or 120I. The grey/white matter ratio increased by 7.3% and 16.3%, respectively. The greater reduction of the FWTM compared to FWHM in 68Ga or 120I line-spread images was in agreement with the improved contrast of 68Ga or 120I images. Notwithstanding elongations seen in the z-direction of 68Ga or 120I point source images acquired in foam, brain phantom images show no comparable extension. Our experimental study confirms that integrated MR-PET delivers improved PET image resolution and contrast for medium- and high-energy positron emitters even though the positron range is reduced only in directions perpendicular to the magnetic field.

Understanding cerebral oxygen metabolism is of great importance in both clinical diagnosis and animal experiments because oxygen is a fundamental source of brain energy and supports brain functional activities. Since small animals such as rats are widely used to study various diseases including cerebral ischemia, cerebrovascular diseases, and neurodegenerative diseases, the development of a noninvasive in vivo measurement method of cerebral oxygen metabolic parameters such as oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) as well as cerebral blood flow (CBF) and cerebral blood volume (CBV) has been a priority. Although positron emission tomography (PET) with 15O labeled gas tracers has been recognized as a powerful way to evaluate cerebral oxygen metabolism in humans, this method could not be applied to rats due to technical problems and there were no reports of PET measurement of cerebral oxygen metabolism in rats until an 15O-O2 injection method was developed a decade ago. Herein, we introduce an intravenous administration method using two types of injectable 15O-O2 and an 15O-O2 gas inhalation method through an airway placed in the trachea, which enables oxygen metabolism measurements in rats.

Positron emission tomography with 15O-labeled gases (15O-PET) is important for in vivo measurement of cerebral oxygen metabolism both in clinical and basic settings. However, there are currently no reports concerning 15O-PET in mice. Here, we developed an 15O-PET method applicable to mice with spontaneous respiration of 15O-gas without a tracheotomy catheter. Sequential 115O-PET was also performed in a mouse model of chronic cerebral hypoperfusion with bilateral common carotid artery stenosis (BCAS) induced by placement of microcoils. 15O-gas with isoflurane was supplied to the nose of mouse with evacuation of excess 15O-gas surrounding the body. 15O-PET was performed on days 3, 7, 14, 21, and 28 after surgery. Cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) were calculated in whole brains. A significant decrease in CBF and compensatory increase in OEF in the BCAS group produced CMRO2 values comparable to that of the sham group at three days post-operation. Although CBF and OEF in the BCAS group gradually recovered over the first 28 days, the CMRO2 showed a gradual decrease to 68% of sham values at 28 days post-operation. In conclusion, we successfully developed a noninvasive 15O-PET method for mice. [ABSTRACT FROM AUTHOR]

Subcortical white matter (WM) is a frequent target of ischemic injury and extensive WM lesions are important substrates of vascular cognitive impairment (VCI) in humans. However, ischemic stroke rodent models have been shown to mainly induce cerebral infarcts in the gray matter, while cerebral hypoperfusion models show only WM rarefaction without infarcts. The lack of animal models consistently replicating WM infarct damage may partially explain why many neuroprotective drugs for ischemic stroke or VCI have failed clinically, despite earlier success in preclinical experiments. Here, we report a novel animal model of WM infarct damage with cognitive impairment can be generated by surgical implantation of different devices to the right and left common carotid artery (CCA) in C57BL/6J mice. Implantation of an ameroid constrictor to the right CCA resulted in gradual occlusion of the vessel over 28 d, whereas placement of a microcoil to the left CCA induced ~50% arterial stenosis. Arterial spin labeling showed a gradual reduction of cerebral blood flow over 28 d post operation. Such reductions were more marked in the right, compared with the left, hemisphere and in subcortical, rather than the cortical, areas. Histopathological analysis showed multiple infarct damage in right subcortical regions, including the corpus callosum, internal capsule, hippocampal fimbria, and caudoputamen, in 81% of mice. Mice displaying such damage performed significantly poorer in locomotor and cognitive tests. The current mouse model replicates the phenotypes of human subcortical VCI, including multiple WM infarcts with motor and cognitive impairment. [ABSTRACT FROM AUTHOR]

Abstract  Myocardial regeneration therapy shows great promise as a treatment for heart failure. We recently introduced combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells as a treatment for human ischemic cardiomyopathy. We report the results of our first clinical trial of this technique, used to treat a patient with severe heart failure caused by ischemic cardiomyopathy who was being managed with a left ventricular assist system (LVAS). After combined cell transplantation, the patient showed signs of improved cardiac performance and angiogenesis, and reduced fibrosis. [ABSTRACT FROM AUTHOR]

We investigated a new method for the synthesis of [15O]CO and [15O]CO2 that did not require heating, which might be useful for rapid supply in clinical use. The target gas, N2 with a small amount of added CO, was irradiated with deuteron to give [15O]CO. The [15O]CO2 was produced by passing a mixture of the purified [15O]CO and dry O2 through a manganese dioxide–cupric oxide (MnO2–CuO) catalyst at room temperature. The chemical yields of [15O]CO and [15O]CO2 of the new method were 4.5±0.1 and 4.0±0.1 MBq/ml, respectively, and were higher than those of conventional methods (1.9±0.1 MBq/ml of [15O]CO and 3.6±0.1 MBq/ml of [15O]CO2). The radiochemical purities of both [15O]CO and [15O]CO2 were over 99.9%. Each quality of [15O]CO and [15O]CO2 was suitable for clinical PET. The new method would remarkably shorten the preparation time for [15O]CO and [15O]CO2 production. Namely, the start of inhalation of the [15O]gases is not restricted by the production procedure of [15O]CO and [15O]CO2. [Copyright &y& Elsevier]

Presents a study that investigated the effects of attenuation correction and scatter correction on regional cerebral blood flow values with [sup99]Tc-Ethyl cysteinate dimer (ECD) single photon emission computed tomography. Evaluation of the applicability of uniform attenuation maps (UAM); Technique used for scatter correction; Adequacy of using a UAM generated with ECD images.

Monte Carlo simulation is widely applied to evaluate the performance of three-dimensional positron emission tomography (3D-PET). For accurate scatter simulations, all components that generate scatter need to be taken into account. The aim of this work was to identify the components that influence scatter. The simulated geometries of a PET scanner were: a precisely reproduced configuration including all of the components; a configuration with the bed, the tunnel and shields; a configuration with the bed and shields; and the simplest geometry with only the bed. We measured and simulated the scatter fraction using two different set-ups: (1) as prescribed by NEMA-NU 2007 and (2) a similar set-up but with a shorter line source, so that all activity was contained only inside the field-of-view (FOV), in order to reduce influences of components outside the FOV. The scatter fractions for the two experimental set-ups were, respectively, 45% and 38%. Regarding the geometrical configurations, the former two configurations gave simulation results in good agreement with the experimental results, but simulation results of the simplest geometry were significantly different at the edge of the FOV. From the simulation of the precise configuration, the object (scatter phantom) was the source of more than 90% of the scatter. This was also confirmed by visualization of photon trajectories. Then, the bed and the tunnel were mainly the sources of the rest of the scatter. From the simulation results, we concluded that the precise construction was not needed; the shields, the tunnel, the bed and the object were sufficient for accurate scatter simulations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cerebral blood flow (CBF) obtained by dynamic susceptibility contrast MRI (DSC-MRI) often provides an abnormal contrast between normal and ischemic areas, as compared with those from positron emission tomography (PET) or SPECT. A linear relationship is normally assumed in the transverse relaxation rate change in relation to the regional concentration of the contrast agent. This study was intended to evaluate this assumption. The impact of an alternative, non-linear model based on a realistic capillary structure was also evaluated in the assessment of CBV and CBF by use of DSC-MRI. DSC-MRI and 15O-PET were carried out on 13 patients with chronic cerebrovascular disease. Regions-of-interest (ROI) were selected both in the ischemic and unaffected hemispheres, and the left-to-right (L/R) ratios of CBF and CBV were compared between PET and DSC-MRI. When assuming the linear relationship, the contrast of CBF by DSC-MRI was lower than that by PET (CBFL/R,MRI=0.60CBFL/R,PET+0.40, r=0.63, p<0.0216), and the contrast of CBV by DSC-MRI greater than that by PET (CBVL/R,MRI=1.34CBVL/R,PET-0.33, r=0.84, p=0.0003). Disagreement of CBF was particularly apparent in the area of enhanced CBV. The employment of the non-linear model improved the agreement between DSC-MRI and PET for both CBF and CBV (CBFL/R,MRI=0.89CBFL/R,PET+0.08, r=0.93, p<0.0001; CBVL/R,MRI=1.03CBVL/R,PET-0.04, r=0.79, p=0.0014). These results suggest that the linear model has limited accuracy in the assessment of CBF and CBV in patients with chronic cerebrovascular disease, and that the non-linear correction is essential in order to provide accurate quantitation with DSC-MRI. [Copyright &y& Elsevier]

The values of cerebral blood flow (CBF) and vascular volume (V0) can be estimated using H215O dynamic PET and the two-compartment model. In this study, we present a method that can generate parametric images of both CBF and V0, with improvement of image quality, by a single computational procedure. This method is based on the two-compartment model, and employs linear least square algorithm and cluster analysis for parameter estimation and suppressing noise on image data, respectively. The results in computer simulation showed that this method could provide the reduction of error in parameter estimation, as well as noise on parametric images of both CBF and V0, and the smaller effect of changes of CBF and V0 on the estimation of both parameters. In the PET study, this method could provide the images of CBF and V0 with improvement in quality, compared with those without clustering by showing the clear location of arterial vascular components on the V0 image. In the simulation, the error in parameter estimation was sufficiently small for K1, but not for V0. These results reveal that the presented method has the potential to make a contribution to the improved diagnosis of cerebral vascular disease and activation. [Copyright &y& Elsevier]

Recently, techniques for converting site-specific normal databases to other databases have been required for SPECT image statistical analysis. To implement scatter correction, we developed an image conversion technique named image-based scatter correction (IBSC). Furthermore, we evaluated the applicability of IBSC for SPM analysis. SPECT studies were performed on 28 normal volunteers and 10 patients with Alzheimer''s disease (AD) using 123I-IMP. Two sets of scatter uncorrected images, IACμb, and a corrected image by TEW, ITEW, were reconstructed with attenuation correction using Chang''s method. Scatter corrected images by IBSC, IIBSC, were generated from IACμb. Normal databases of IACμb, ITEW and IIBSC were compared by SPM analysis. The Z-score (=(mean-AD)/S.D.) of ITEW was compared with that of IACμb. Significant differences (p<0.05) between normal databases of IACμb and ITEW observed at the global posterior cingulate and precuneus regions almost disappeared when ITEW and IIBSC were compared. The Z-score at the posterior cingulate by ITEW was increased compared with that of IACμb. We conclude that for SPM analysis of IMP-SPECT, IBSC can convert a normal database of scatter uncorrected images into corrected images, which is equivalent to correction by a conventional TEW method. Scatter correction may improve the ability to detect AD. [Copyright &y& Elsevier]

The rupture of atherosclerotic plaques and the resultant thrombus formation are mainly responsible for myocardial and cerebral infarctions. Thus, the detection of vulnerable plaques in atherosclerotic lesions has been desired, and attempts to image them with [18F]FDG are ongoing. Intimal thickening can be observed both in stable and vulnerable plaques; however, in vulnerable plaque, the lesion is inflamed, and the infiltrated macrophages cause the rupture of such plaques. In this study, we investigated whether [18F]FDG-PET could specifically detect the vulnerable plaque, other than stable plaque, or not using an animal model of atherosclerosis, the Watanabe heritable hyperlipidemic (WHHL) rabbit. A helical CT angiogram was acquired at 180 min postinjection of [18F]FDG, and PET scanning was carried out for 15 min from 210 min postinjection of [18F]FDG. At 4 h postinjection of the radiotracer, the aortas were removed, and the radioactivity was measured. Then, each arterial segment was embedded in paraffin, and consecutive 5-μm-thick slices were prepared. They were subjected to Azan–Mallory staining or immunohistochemical staining for measurement of intimal thickness and macrophage number. In the aortas of the WHHL rabbits, intense [18F]FDG radioactivity was detected with PET, while little radioactivity was seen in the aortas of control rabbits. Actually, in the removed aortic segments [18F]FDG accumulated significantly higher in the aortas of the WHHL rabbits than in those of the control rabbits. Furthermore, in the atherosclerotic lesions of the WHHL rabbits, the [18F]FDG uptake was well correlated with macrophage number. On the other hand, the correlation between [18F]FDG uptake and the area ratio of the intima to the whole cross-section was poor. These results suggest that the detected radioactivity with [18F]FDG-PET in the atherosclerotic lesion is associated with macrophage density. Since macrophages are responsible for plaque vulnerability, [18F]FDG imaging should be useful for selective detection of vulnerable plaques. [Copyright &y& Elsevier]