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3Purpose: We analyzed the performance of the Inveon for an integrated small-animal PET/SPECT/CT system and compared the imaging capabilities of the SPECT and the PET components.Methods: For SPECT, energy resolution, tomographic spatial resolution, and system sensitivity were evaluated with 99m Tc solution using a single pinhole collimator. For PET, spatial resolution, absolute sensitivity, scatter fraction, and peak noise equivalent count (NEC) were evaluated. A micro-Derenzo phantom, cylindrical phantom, and National Electrical Manufacturers Association NU-4 image quality phantom were scanned to compare SPECT and PET image capabilities, and SPECT and PET bone imaging were performed on a normal rat in vivo.Results: SPECT spatial resolution was 0.84 mm full width at half maximum (FWHM) at a radius of rotation of 25 mm using the 0.5-mm pinhole aperture collimator, while PET spatial resolution was 1.63 mm FWHM at the center. SPECT system sensitivity at a radius of rotation of 25 mm was 35.3 cps/MBq (4 × 10 -3 %) using 0.5-mm pinhole aperture, while PET absolute sensitivity was 3.2% for 350-650 keV and 3.432 ns. Accordingly, the volume sensitivity of PET was three orders of magnitude 4 higher than that of SPECT.Conclusions: This integrated PET/SPECT/CT system provided high system performance with excellent spatial resolution for SPECT and sensitivity for PET.Based on tracer availability and system performance, SPECT and PET have complementary roles for multi-modality small-animal imaging.Key Words: integrated PET/SPECT/CT system; small-animal imaging; performance measurement; instrumentation; molecular imaging 5 INTRODUCTIONMolecular imaging of small laboratory animals using single photon emission tomography (SPECT), positron emission tomography (PET), and x-ray computed tomography (CT) has recently emerged as an important tool for the in vivo study of animal models of human disease. This imaging method enables longitudinal studies to be performed in the same animal, and animals can serve as their own control.SPECT and PET have been used in functional imaging, including brain, heart, gene expression, and oncology studies [1,2]. CT has also been used for anatomical imaging (e.g., bone imaging) because it provides high contrast between bone and soft tissue [3]. The use of SPECT, PET, and CT in combinations such as SPECT/CT, PET/CT, SPECT/PET, and SPECT/PET/CT-so-called "multi-modality imaging"-may enable the development of new and interesting protocols for investigating many biological phenomena more effectively than is possible using SPECT, PET, or CT modalities alone. Using these techniques, lesions visualized by functional imaging can be correlated with anatomic imaging. In general, CT is also used for attenuation and scatter correction of SPECT and PET images. However, in this 6 study, neither attenuation nor scatter correction was performed.Integration of SPECT, PET, and CT images can be achieved by a "software approach" that fuses the images acquired by separate scanners. These techniques, however, are hamper...

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas.Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that 18 F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO PET for the differential diagnosis of GBM from lower grade gliomas. Methods: This prospective study included 23 patients with pathologically confirmed gliomas. All the patients underwent FMISO PET and FDG PET within a week. FMISO images were acquired 4 hours after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion-to-normal tissue ratios and FMISO uptake volume were calculated. Results: Thirteen of the 23 glioma patients were diagnosed as having GBM (grade IV glioma in WHO classification 2007), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all the GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p<0.001). One GBM patient was excluded 2 from FDG PET study because of hyperglycemia. All the GBM patients and 3 of the 9 (33 %) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 % and 100 % for FMISO, and 100 % and 66 % for FDG, respectively. The lesion-to-cerebellum ratio of FMISO uptake was higher in GBM patients (2.74±0.60, range: 1.71 -3.81) than in non-GBM patients (1.22±0.06, range: 1.09 -1.29, p<0.001) with no overlap between the groups. The lesion-to-gray matter ratio of FDG was also higher in GBM patients (1.46±0.75, range: 0.91 -3.79) than in non-GBM patients (1.07±0.62, range: 0.66 -2.95, p<0.05); however, overlap of the ranges did not allow clear differentiation between GBM and non-GBM. Uptake volume of FMISO was larger in GBM (27.18±10.46 %, range: 14.02 -46.67 %) than in non-GBM (6.07±2.50 %, range: 2.12 -9.22 %, p<0.001). Conclusion: These preliminary data suggest that FMISO PET may distinguish GBM from lower grade gliomas.

This study aimed to assess whether 18 F-FDG PET could serially monitor the beneficial effects of bone marrow stromal cells (BMSC) on cerebral glucose metabolism when transplanted into the infarct brain of rats. Methods: The BMSC from green fluorescent protein transgenic rats or vehicle was stereotactically transplanted into the ipsilateral striatum at 7 d after permanent middle cerebral artery occlusion of rats. Local glucose metabolism was semiquantitatively measured at 6 and 35 d after ischemia using 18 F-FDG PET. Motor function was serially evaluated throughout the experiments. At 35 d after ischemia, immunohistochemistry was performed to evaluate the phenotype of BMSC and their effects on the expression of brain-type glucose transporters. Results: BMSC transplantation not only enhanced functional recovery but also promoted the recovery of glucose utilization in the periinfarct area when stereotactically transplanted at 1 wk after ischemia. The engrafted cells were widely distributed, and most expressed a neuron-specific protein, NeuN. BMSC transplantation also prevented the pathologic upregulation of glucose transporters in the periinfarct neocortex. Conclusion: The present findings strongly suggest that the BMSC may enhance functional recovery by promoting the recovery of local glucose metabolism in the periinfarct area when directly transplanted into the infarct brain at clinically relevant timing. The BMSC also inhibit the pathologic upregulation of brain-isoform glucose transporters type 1 and 3. 18 F-FDG PET may be a valuable modality to scientifically prove the beneficial effects of BMSC transplantation on the host brain in clinical situations.

Background: Vulnerable and inflamed plaques in the carotid artery are at high risk of ischemic stroke, suggesting the importance of diagnostic modalities to detect them in patients with carotid stenosis with high sensitivity and specificity. Although many investigators have reported that magnetic resonance imaging (MRI) is a useful tool to predict the vulnerable components of carotid plaque, its validity is not established. On the other hand, ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) may be an alternative modality to directly identify the inflamed plaque in carotid artery stenosis. Therefore, this study aimed at evaluating the validity of MRI and FDG-PET to predict vulnerable and inflamed carotid plaque. Methods: This prospective study totally included 25 patients who underwent carotid endarterectomy (CEA) for carotid artery stenosis at our institute between January 2009 and January 2012. Prior to CEA, FDG-PET, black-blood T1-weighted imaging (BB-T1WI), and 3-dimensional time-of-flight (TOF) imaging were performed. The specimens were stained with hematoxylin-eosin to assess the different plaque components (lipid, hemorrhage, calcification, and fibrous tissue). In addition, they were stained with primary antibodies against CD68 (activated macrophages) and matrix metalloproteinase (MMP)-9. Results: High FDG uptake was detected in 13 (52.0%) of 25 patients. All of them had lipid-rich plaque. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to identify the lipid-rich plaques were all 100% for FDG-PET. More importantly, all of the FDG-positive plaques had strong immunoreactivity against both CD68 and MMP-9. There was a significant correlation between the findings on FDG-PET and those on immunohistochemistry against CD68 and MMP-9 (p = 0.006 and 0.004, respectively). On the other hand, 16 (64.0%) of 25 patients had high signal intensity plaque on BB-T1WI. In 7 of these 16 patients, the lesions also showed high signal intensity on TOF imaging. All of them had a large intraplaque hemorrhage. The sensitivity, specificity, PPV, and NPV to identify a large intraplaque hemorrhage were 70, 100, 100, and 83%, respectively, for MRI. Conclusions: These findings suggest that FDG-PET and MRI are complementary to predict high-risk carotid plaque, such as lipid-rich or hemorrhagic plaque. FDG-PET can accurately predict the lipid-rich and inflamed plaque. MRI is valuable to identify unstable plaque with a large intraplaque hemorrhage. The combination of these two modalities may play an important role in predicting carotid plaque at high risk of ischemic stroke.

For better characterization of gliomas and for risk assessment, the results of metabolic PET imaging should be revised after obtaining the pathological report, because oligodendroglial differentiation may positively influence the substrate metabolism and thus complicated the preoperative evaluation.

See an invited perspective on this article on page 781.Diastolic dysfunction is important in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Sympathetic nervous hyperactivity may contribute to the development of diastolic dysfunction. The aim of this study was to determine the relationship between myocardial sympathetic innervation quantified by 11 C-hydroxyephedrine PET and diastolic dysfunction in HFpEF patients. Methods: Forty-one HFpEF patients having an echocardiographic left ventricular ejection fraction of 40% or greater and 12 age-matched volunteers without heart failure underwent the echocardiographic examination and 11 C-hydroxyephedrine PET. Diastolic dysfunction was classified into grades 0-3 by Doppler echocardiography. Myocardial sympathetic innervation was quantified using the 11 C-hydroxyephedrine retention index (RI). The coefficient of variation of 17-segment RIs was derived as a measure of heterogeneity in myocardial 11 C-hydroxyephedrine uptake. Results: Grade 2-3 diastolic dysfunction (DD 2-3 ) was found in 19 HFpEF patients (46%). They had a significantly lower global RI (0.075 6 0.018 min 21 ) than volunteers (0.123 6 0.028 min 21 , P , 0.001) and HFpEF patients with grade 0-1 diastolic dysfunction (DD 0-1 ) (0.092 6 0.024 min 21 , P 5 0.046). HFpEF patients with DD 2-3 had the largest coefficient of variation of 17-segment RIs of the 3 groups (18.4% 6 7.7% vs. 14.1% 6 4.7% in HFpEF patients with DD 0-1 , P 5 0.042 for post hoc tests). In multivariate logistic regression analysis, a lower global RI (odds ratio, 0.66 per 0.01 min 21 ; 95% confidence interval, 0.38-0.99; P 5 0.044) was independently associated with the presence of DD 2-3 in HFpEF patients. Conclusion: Myocardial sympathetic innervation was impaired in HFpEF patients and was associated with the presence of advanced diastolic dysfunction in HFpEF.

FDG-PET/CT demonstrated limited areas of abnormality allowing accurate delineation, and is thus useful to narrow the surgical fields. Since overall diagnostic accuracy of FDG-PET/CT was superior to that of MRI, FDG-PET/CT is a useful technique to narrow the surgical field for successful less invasive surgery.