Small animal PET with spontaneous inhalation of 15O-labelled oxygen gases: Longitudinal assessment of cerebral oxygen metabolism in a rat model of neonatal hypoxic-ischaemic encephalopathy.

Perinatal hypoxic-ischaemic encephalopathy (HIE) is the leading cause of irreversible brain damage resulting in serious neurological dysfunction among neonates. We evaluated the feasibility of positron emission tomography (PET) methodology with 15O-labelled gases without intravenous or tracheal cannulation for assessing temporal changes in cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) in a neonatal HIE rat model. Sequential PET scans with spontaneous inhalation of 15O-gases mixed with isoflurane were performed over 14 days after the hypoxic-ischaemic insult in HIE pups and age-matched controls. CBF and CMRO2 in the injured hemispheres of HIE pups remarkably decreased 2 days after the insult, gradually recovering over 14 days in line with their increase found in healthy controls according to their natural maturation process. The magnitude of hemispheric tissue loss histologically measured after the last PET scan was significantly correlated with the decreases in CBF and CMRO2.This fully non-invasive imaging strategy may be useful for monitoring damage progression in neonatal HIE and for evaluating potential therapeutic outcomes.

Quantitative [99mTc]Tc-MDP SPECT/CT correlated with [18F]NaF PET/CT for bone metastases in patients with prostate cancer.

BACKGROUND: The purpose of the present study was to elucidate the correlation between standardized uptake value (SUV) and volume-based parameters measured by quantitative [99mTc]Tc-methylene diphosphonate (MDP) single photon emission computed tomography (SPECT)/CT and [18F]-sodium fluoride ([18F]NaF) positron emission tomography (PET)/CT in the assessment of bone metastases in patients with prostate cancer. METHODS: The study included 26 male prostate cancer patients with confirmed or suspected bone metastases who underwent both [99mTc]Tc-MDP SPECT/CT and [18F]NaF PET/CT studies. Skeletal lesions visible on both SPECT/CT and PET/CT were classified as benign or metastases. The maximum SUV (SUVmax), peak SUV (SUVpeak), mean SUV (SUVmean), metabolic bone volume (MBV), and total bone uptake (TBU) were calculated for every lesion showing abnormal uptake. RESULTS: A total of 202 skeletal lesions (147 benign and 55 metastases) were detected in the 26 patients. Strong significant correlations were noted between SPECT/CT and PET/CT for the SUV- and volume-based parameters (all P < 0.001). The SUVmax, SUVpeak, SUVmean, and TBU values obtained with SPECT/CT were significantly lower than the corresponding values obtained with PET/CT (all P < 0.001). The MBV in SPECT/CT was significantly higher than that in PET/CT (P < 0.001). All SUV- and volume-based parameters obtained with both SPECT/CT and PET/CT for metastatic lesions were significantly higher than the corresponding parameters for benign lesions (P values from 0.036 to < 0.001). CONCLUSIONS: These preliminary results demonstrate that the SUV- and volume-based parameters for bone uptake obtained with quantitative SPECT/CT and PET/CT are strongly correlated in patients with prostate cancer. The SUV parameters obtained with SPECT/CT were significantly lower than those obtained with PET/CT, whereas the uptake volume obtained with SPECT/CT was significantly higher than that obtained with PET/CT.

Fractal analysis of 11C-methionine PET in patients with newly diagnosed glioma.

BACKGROUND: The present study tested the possible utility of fractal analysis from L-[methyl-11C]-methionine (MET) uptake in patients with newly diagnosed gliomas for differentiating glioma, especially in relation to isocitrate dehydrogenase 1 (IDH1) mutation status, and as compared with the conventional standardized uptake value (SUV) parameters. METHODS: Investigations of MET PET/CT were performed retrospectively in 47 patients with newly diagnosed glioma. Tumors were divided into three groups: lower grade glioma (IDH1-mutant diffuse astrocytoma and IDH1-mutant anaplastic astrocytoma), higher grade glioma (IDH1-wildtype diffuse astrocytoma and IDH1-wildtype anaplastic astrocytoma), and glioblastoma. The fractal dimension for tumor, maximum SUV (SUVmax) for tumor (T) and mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Metabolic tumor volume (MTV) and total lesion MET uptake (TLMU) were also measured. RESULTS: There were significant differences in SUVmax (p = 0.006) and T/N ratio (p = 0.02) between lower grade glioma and glioblastoma. There were no significant differences among any of the three groups in MTV or TLMU. Significant differences were obtained in the fractal dimension between lower grade glioma and higher grade glioma (p = 0.006) and glioblastoma (p < 0.001). CONCLUSIONS: The results of this preliminary study in a small patient population suggest that the fractal dimension using MET PET in patients with newly diagnosed gliomas is useful for differentiating glioma, especially in relation to IDH1 mutation status, which has not been possible with SUV parameters.

Texture Indices of 18F-FDG PET/CT for Differentiating Squamous Cell Carcinoma and Non-Hodgkin's Lymphoma of the Oropharynx.

We assessed the role of 18F-FDG PET/CT texture indices for the differentiation of squamous cell carcinoma (SCC) and non-Hodgkin's lymphoma (NHL) in the oropharynx. 18F-FDG PET/CT data for 27 patients with SCC and 25 patients with NHL in the oropharynx were investigated. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and six texture indices (homogeneity, entropy, short-run emphasis, long-run emphasis, low gray-level zone emphasis [LGZE], and high graylevel zone emphasis [HGZE]) were derived from PET images. PET/CT parameters of the SCC patients were compared with those of the NHL patients. The diagnostic accuracy of the indices for differentiating SCC from NHL was calculated by a receiver operating characteristic curve analysis. 18F-FDG uptake in the oropharynx was observed in all of the patients. The SUVmax, MTV, and TLG did not differ significantly between the SCC and NHL groups, but two of the six texture indices (LGZE [p=0.004] and HGZE [p=0.03]) showed significant differences between the groups. LGZE was the best discriminative index for the differentiation of SCC and NHL (55.6% sensitivity, 88.0% specificity). The LGZE and HGZE texture indices derived from 18F-FDG PET/CT images may be useful in differentiating SCC and NHL in the oropharynx.

Effect of quantitative values on shortened acquisition duration in brain tumor 11C-methionine PET/CT.

BACKGROUND: The amount of signal decreases when the acquisition duration is shortened. However, it is not clear how this affects the quantitative values. This study aims to clarify the effect of acquisition time shortening in brain tumor PET/CT using 11C-methionine on the quantitative values. METHOD: This study was a retrospective analysis of 30 patients who underwent clinical 11C-methionine PET/CT examination. PET images were acquired in list mode for 10 min. PET images of acquisition duration from 1 to 10 min with 1-min step were reconstructed. We examined the effect on the quantitative values of acquisition duration. We placed a volume of interest to include the entire tumor and regions of interest in the shape of a large crescent in the contralateral hemisphere in 5 contiguous axial slices as normal tissue. Quantitative values examined were maximum, peak, and mean standardized uptake values (SUVmax, SUVpeak, SUVmean), metabolic tumor volume (MTV), and maximum tumor to normal tissue ratio (TNRmax), with each duration compared to that with 10 min. RESULTS: SUVmax, MTV, and TNRmax showed the highest values due to the effects of statistical noise when the acquisition time was 1 min. These values were stable when the acquisition duration was > 6 min. SUVpeak and SUVmean showed mostly consistent values regardless of duration. CONCLUSIONS: SUVmax, MTV, and TNRmax are affected by acquisition time. If the acquisition duration was > 6 min, the fluctuation could be suppressed within 5% in these quantitative values. However, SUVpeak was suggested to be a robust index regardless of the acquisition duration.

Multiple positron emission tomography tracers for use in the classification of gliomas according to the 2016 World Health Organization criteria.

BACKGROUND: The molecular diagnosis of gliomas such as isocitrate dehydrogenase (IDH) status (wild-type [wt] or mutation [mut]) is especially important in the 2016 World Health Organization (WHO) classification. Positron emission tomography (PET) has afforded molecular and metabolic diagnostic imaging. The present study aimed to define the interrelationship between the 2016 WHO classification of gliomas and the integrated data from PET images using multiple tracers, including 18F-fluorodeoxyglucose (18F-FDG), 11C-methionine (11C-MET), 18F-fluorothymidine (18F-FLT), and 18F-fluoromisonidazole (18F-FMISO). METHODS: This retrospective, single-center study comprised 113 patients with newly diagnosed glioma based on the 2016 WHO criteria. Patients were divided into 4 glioma subtypes (Mut, Codel, Wt, and glioblastoma multiforme [GBM]). Tumor standardized uptake value (SUV) divided by mean normal cortical SUV (tumor-normal tissue ratio [TNR]) was calculated for 18F-FDG, 11C-MET, and 18F-FLT. Tumor-blood SUV ratio (TBR) was calculated for 18F-FMISO. To assess the diagnostic accuracy of PET tracers in distinguishing glioma subtypes, a comparative analysis of TNRs and TBR as well as the metabolic tumor volume (MTV) were calculated by Scheffe's multiple comparison procedure for each PET tracer following the Kruskal-Wallis test. RESULTS: The differences in mean 18F-FLT TNR and 18F-FMISO TBR were significant between GBM and other glioma subtypes (P < .001). Regarding the comparison between Gd-T1WI volumes and 18F-FLT MTVs or 18F-FMISO MTVs, we identified significant differences between Wt and Mut or Codel (P < .01). CONCLUSION: Combined administration of 4 PET tracers might aid in the preoperative differential diagnosis of gliomas according to the 2016 WHO criteria.

Texture indices of 4'-[methyl-11C]-thiothymidine uptake predict p16 status in patients with newly diagnosed oropharyngeal squamous cell carcinoma: comparison with 18F-FDG uptake.

BACKGROUND: In oropharyngeal squamous cell carcinoma (OPSCC), human papillomavirus (HPV)/p16 status is important as a prognostic biomarker. PURPOSE: We evaluated the relationship between 4'-[methyl-11C]-thiothymidine (11C-4DST) and 18F-FDG PET texture indices and p16 status in patients with newly diagnosed OPSCC. METHODS: We retrospectively reviewed the collected data of 256 consecutive, previously untreated patients with primary head and neck tumors enrolled between November 2011 and October 2019. Complete data on both 11C-4DST and 18F-FDG PET/CT studies before therapy, patients with OPSCC, and p16 status were available for 34 patients. Six of them were excluded because they did not exhibit sufficient 11C-4DST and/or 18F-FDG tumor uptake to perform textural analysis. Finally, 28 patients with newly diagnosed OPSCC were investigated. The maximum standardized uptake value (SUVmax) and 6 texture indices (homogeneity, entropy, short-run emphasis, long-run emphasis, low gray-level zone emphasis, and high gray-level zone emphasis) were derived from PET images. The presence of p16 expression in tumor specimens was examined by immunohistochemistry and compared with the PET parameters. RESULTS: Using 11C-4DST, the expression of p16 was associated with a higher homogeneity (P = 0.012), lower short-run emphasis (P = 0.005), higher long-run emphasis (P = 0.009), and lower high-gray-level-zone emphasis (P = 0.042) values. There was no significant difference between 18F-FDG PET parameters and p16 status. CONCLUSION: Texture indices of the primary tumor on 11C-4DST PET, but not 18F-FDG PET, may be of value in predicting the condition's p16 status in patients with newly diagnosed OPSCC.

68Ga-DOTA chelate, a novel imaging agent for assessment of myocardial perfusion and infarction detection in a rodent model.

BACKGROUND: Magnetic resonance imaging (MRI) with Gadolinium 1,4,7,10-tetraazacyclododecane-N',N″,N''',N″″-tetraacetic acid (Gd-DOTA) enables assessment of myocardial perfusion during first-pass of the contrast agent, while increased retention can signify areas of myocardial infarction (MI). We studied whether Gallium-68-labeled analog, 68Ga-DOTA, can be used to assess myocardial perfusion on positron emission tomography/computed tomography (PET/CT) in rats, comparing it with 11C-acetate. METHODS: Rats were studied with 11C-acetate and 68Ga-DOTA at 24 hours after permanent ligation of the left coronary artery or sham operation. One-tissue compartmental models were used to estimate myocardial perfusion in normal and infarcted myocardium. After the PET scan, hearts were sectioned for autoradiographic detection of 68Ga-DOTA distribution. RESULTS: 11C-acetate PET showed perfusion defects and histology showed myocardial necrosis in all animals after coronary ligation. Kinetic modeling of 68Ga-DOTA showed significantly higher k1 values in normal myocardium than in infarcted areas. There was a significant correlation (r = 0.82, P = 0.001) between k1 values obtained with 68Ga-DOTA and 11C-acetate. After 10 minutes of tracer distribution, the 68Ga-DOTA concentration was significantly higher in the infarcted than normal myocardium on PET imaging and autoradiography. CONCLUSIONS: Our results indicate that acute MI can be detected as reduced perfusion, as well as increased late retention of 68Ga-DOTA.

Radiosynthesis of 18F-labeled d-allose.

Rare sugars are defined as monosaccharides that exist in nature but are only present in limited quantities. d-Allose is a rare sugar that has been reported to have some unique physiological effects. The present study describes suitable synthetic procedures for novel rare sugars of d-allose that are 18F-labeled at the C-3 and C-6 positions and the preparation of the appropriate labeling precursors. The goal is to facilitate in vivo, noninvasive positron emission tomography (PET) investigation of the behavior of rare sugar analogs of d-allose in organs. We found five precursors that were practical for labeling, three for 3-deoxy-3-[18F]fluoro-d-allose ([18F]3FDA) and two for 6-deoxy-6-[18F]fluoro-d-allose ([18F]6FDA). With manual operation synthesis, the highest radiochemical conversion rates were 75% for [18F]3FDA with a precursor of 1,2,4,6-tetra-O-acetyl-3-O-trifluoromethanesulfonyl-ß-d-glucopyranose and 69% for [18F]6FDA with a precursor of 1,2,3,4-tetra-O-acetyl-6-O-trifluoromethanesulfonyl-ß-d-allopyranose. Furthermore, the practical yields of [18F]3FDA and [18F]6FDA using an automated synthesizer were also investigated. Radiochemical yields of 67% and 49% were obtained for [18F]3FDA and [18F]6FDA, respectively, in an automated synthesizer. As basic assessment of stability for use in PET scanning, high performance liquid chromatography analysis showed no decomposition of [18F]3FDA and [18F]6FDA after up to 6 h in rabbit blood plasma.

Myocardial Blood Flow and Metabolic Rate of Oxygen Measurement in the Right and Left Ventricles at Rest and During Exercise Using 15O-Labeled Compounds and PET.

Aims: Simultaneous measurement of right (RV) and left ventricle (LV) myocardial blood flow (MBF), oxygen extraction fraction (OEF), and oxygen consumption (MVO2) non-invasively in humans would provide new possibilities to understand cardiac physiology and different patho-physiological states. Methods: We developed and tested an optimized novel method to measure MBF, OEF, and MVO2 simultaneously both in the RV and LV free wall (FW) using positron emission tomography in healthy young men at rest and during supine bicycle exercise. Results: Resting MBF was not significantly different between the three myocardial regions. Exercise increased MBF in the LVFW and septum, but MBF was lower in the RV compared to septum and LVFW during exercise. Resting OEF was similar between the three different myocardial regions (~70%) and increased in response to exercise similarly in all regions. MVO2 increased approximately two to three times from rest to exercise in all myocardial regions, but was significantly lower in the RV during exercise as compared to septum LVFW. Conclusion: MBF, OEF, and MVO2 can be assessed simultaneously in the RV and LV myocardia at rest and during exercise. Although there are no major differences in the MBF and OEF between LV and RV myocardial regions in the resting myocardium, MVO2 per gram of myocardium appears to be lower the RV in the exercising healthy human heart due to lower mean blood flow. The presented method may provide valuable insights for the assessment of MBF, OEF and MVO2 in hearts in different pathophysiological states.

Liver blood dynamics after bariatric surgery: the effects of mixed-meal test and incretin infusions.

AIMS/HYPOTHESIS: The mechanisms for improved glycemic control after bariatric surgery in subjects with type 2 diabetes (T2D) are not fully known. We hypothesized that dynamic hepatic blood responses to a mixed-meal are changed after bariatric surgery in parallel with an improvement in glucose tolerance. METHODS: A total of ten morbidly obese subjects with T2D were recruited to receive a mixed-meal and a glucose-dependent insulinotropic polypeptide (GIP) infusion before and early after (within a median of less than three months) bariatric surgery, and hepatic blood flow and volume (HBV) were measured repeatedly with combined positron emission tomography/MRI. Ten lean non-diabetic individuals served as controls. RESULTS: Bariatric surgery leads to a significant decrease in weight, accompanied with an improved ß-cell function and glucagon-like peptide 1 (GLP-1) secretion, and a reduction in liver volume. Blood flow in portal vein (PV) was increased by 1.65-fold (P = 0.026) in response to a mixed-meal in subjects after surgery, while HBV decreased in all groups (P < 0.001). When the effect of GIP infusion was tested separately, no change in hepatic arterial and PV flow was observed, but HBV decreased as seen during the mixed-meal test. CONCLUSIONS/INTERPRETATION: Early after bariatric surgery, PV flow response to a mixed-meal is augmented, improving digestion and nutrient absorption. GIP influences the post-prandial reduction in HBV thereby diverting blood to the extrahepatic sites.

Increased Liver Fatty Acid Uptake Is Partly Reversed and Liver Fat Content Normalized After Bariatric Surgery.

OBJECTIVE: Changes in liver fatty acid metabolism are important in understanding the mechanisms of diabetes remission and metabolic changes after bariatric surgery. RESEARCH DESIGN AND METHODS: Liver fatty acid uptake (LFU), blood flow, and fat content (LFC) were measured in 25 obese subjects before bariatric surgery and 6 months after using positron emission tomography/computed tomography and MRS; 14 lean individuals served as the control subjects. RESULTS: The increased LFU in obese subjects was associated with body adiposity. LFU was reduced postoperatively but was still high compared with the control subjects. LFC was normalized. Liver blood flow (per unit volume) was higher in obese subjects than in the control subjects at baseline and was further increased postoperatively; however, the total organ blood flow was unchanged as the liver volume decreased. CONCLUSIONS: The findings suggest that in a postoperative state, intrahepatic fatty acids are not stored in the liver but are used for oxidation to provide energy. Changes in perfusion may contribute to improved liver metabolism postoperatively.

Reconstruction of input functions from a dynamic PET image with sequential administration of 15O2 and [Formula: see text] for noninvasive and ultra-rapid measurement of CBF, OEF, and CMRO2.

CBF, OEF, and CMRO2 images can be quantitatively assessed using PET. Their image calculation requires arterial input functions, which require invasive procedure. The aim of the present study was to develop a non-invasive approach with image-derived input functions (IDIFs) using an image from an ultra-rapid O2 and C15O2 protocol. Our technique consists of using a formula to express the input using tissue curve with rate constants. For multiple tissue curves, the rate constants were estimated so as to minimize the differences of the inputs using the multiple tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects ( n = 24). The estimated IDIFs were well-reproduced against the measured ones. The difference in the calculated CBF, OEF, and CMRO2 values by the two methods was small (<10%) against the invasive method, and the values showed tight correlations ( r = 0.97). The simulation showed errors associated with the assumed parameters were less than ∼10%. Our results demonstrate that IDIFs can be reconstructed from tissue curves, suggesting the possibility of using a non-invasive technique to assess CBF, OEF, and CMRO2.

Fully parametric imaging with reversible tracer 18F-FLT within a reasonable time.

PET enables quantitative imaging of the rate constants K 1, k 2, k 3, and k 4, with a reversible two tissue compartment model (2TCM). A new method is proposed for computing all of these rates within a reasonable time, less than 1 min. A set of differential equations for the reversible 2TCM was converted into a single formula consisting of differential and convolution terms. The validity was tested on clinical data with 18F-FLT PET for patients with glioma (n = 39). Parametric images were generated with the formula that was developed. Parametric values were extracted from regions of interest (ROIs) for glioma from the images generated, and they were compared with those obtained with the non-linear fitting method. We performed simulation studies for testing accuracy by generating simulated images, assuming clinically expected ranges of the parametric values. The computation time was about 20 s, and the quality of the images generated was acceptable. The values obtained for K 1 for grade IV tumor were 0.24 ± 0.23 and 0.26 ± 0.25 ml-1 min-1 g-1 for the image-based and ROI-based methods, respectively. The values were 0.21 ± 0.12 and 0.21 ± 0.12 min-1 for k 2, 0.13 ± 0.07 and 0.13 ± 0.07 min-1 for k 3, and 0.052 ± 0.020 and 0.054 ± 0.021 min-1 for k 4. The differences between the methods were not significant. Regression analysis showed correlations of r = 0.94, 0.86, 0.71, and 0.52 for these parameters. Simulation demonstrated that the accuracy was within acceptable ranges, namely, the correlations were r = 0.99, r = 0.97, r = 0.99, and r = 0.91 for K 1, k 2, k 3, and k 4, respectively, between estimated and assumed values. This results suggest that parametric images can be obtained fully within reasonable time, accuracy, and quality.

Intratumoral heterogeneity of 18F-FLT uptake predicts proliferation and survival in patients with newly diagnosed gliomas.

BACKGROUND: The nucleoside analog 3'-deoxy-3'-18F-fluorothymidine (FLT) has been investigated for evaluating tumor proliferating activity in brain tumors. We evaluated FLT uptake heterogeneity using textural features from the histogram analysis in patients with newly diagnosed gliomas and examined correlation of the results with proliferative activity and patient prognosis, in comparison with the conventional PET parameters. METHODS: FLT PET was investigated in 37 patients with newly diagnosed gliomas. The conventional parameters [tumor-to-contralateral normal brain tissue (T/N) ratio and metabolic tumor volume (MTV)] and textural parameters (standard deviation, skewness, kurtosis, entropy, and uniformity) were derived from FLT PET images. Linear regression analysis was used to compare PET parameters and the proliferative activity as indicated by the Ki-67 index. The associations between parameters and overall survival (OS) were tested by Cox regression analysis. RESULTS: Median OS was 662 days. For the conventional parameters, linear regression analysis indicated a significant correlation between T/N ratio and Ki-67 index (p = 0.02) and MTV and Ki-67 index (p = 0.02). Among textural parameters, linear regression analysis indicated a significant correlation for kurtosis (p = 0.003), entropy (p < 0.001), and uniformity (p < 0.001) as compared to Ki-67 index, exceeding those of the conventional parameters. The results of univariate analysis suggested that skewness and kurtosis were associated with OS (p = 0.03 and 0.02, respectively). Mean survival for patients with skewness values less than 0.65 was 1462 days, compared with 917 days for those with values greater than 0.65 (p = 0.02). Mean survival for patients with kurtosis values less than 6.16 was 1616 days, compared with 882 days for those with values greater than 6.16 (p = 0.006). CONCLUSIONS: Based on the results of this preliminary study in a small patient population, textural features reflecting heterogeneity on FLT PET images seem to be useful for the assessment of proliferation and for the potential prediction of survival in newly diagnosed gliomas.

Reconstruction of an input function from a dynamic PET water image using multiple tissue curves.

Quantification of cerebral blood flow (CBF) is important for the understanding of normal and pathologic brain physiology. When CBF is assessed using PET with [Formula: see text] (15)O or C(15)O2, its calculation requires an arterial input function, which generally requires invasive arterial blood sampling. The aim of the present study was to develop a new technique to reconstruct an image derived input function (IDIF) from a dynamic [Formula: see text] (15)O PET image as a completely non-invasive approach. Our technique consisted of using a formula to express the input using tissue curve with rate constant parameter. For multiple tissue curves extracted from the dynamic image, the rate constants were estimated so as to minimize the sum of the differences of the reproduced inputs expressed by the extracted tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects (n = 29) and was compared to the blood sampling method. Simulation studies were performed to examine the magnitude of potential biases in CBF and to optimize the number of multiple tissue curves used for the input reconstruction. In the PET study, the estimated IDIFs were well reproduced against the measured ones. The difference between the calculated CBF values obtained using the two methods was small as around <8% and the calculated CBF values showed a tight correlation (r = 0.97). The simulation showed that errors associated with the assumed parameters were <10%, and that the optimal number of tissue curves to be used was around 500. Our results demonstrate that IDIF can be reconstructed directly from tissue curves obtained through [Formula: see text] (15)O PET imaging. This suggests the possibility of using a completely non-invasive technique to assess CBF in patho-physiological studies.

Correlation of 4'-[methyl-(11)C]-thiothymidine uptake with Ki-67 immunohistochemistry and tumor grade in patients with newly diagnosed gliomas in comparison with (11)C-methionine uptake.

OBJECTIVE: A novel radiopharmaceutical, 4'-[methyl-(11)C]thiothymidine ((11)C-4DST), has been developed as an in vivo cell proliferation marker based on the DNA incorporation method. The purpose of this study was to evaluate (11)C-4DST uptake in patients with newly diagnosed glioma and to correlate the results with proliferative activity and tumor grade, in comparison with L-[methyl-(11)C]-methionine ((11)C-MET). METHODS: Investigations of (11)C-4DST and (11)C-MET PET/CT were performed retrospectively in 23 patients with newly diagnosed glioma. The maximum standardized uptake value (SUVmax) for tumor (T) and the mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Metabolic tumor volume (MTV) was defined as the volume with a threshold of 40% of the SUVmax. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. RESULTS: Of 23 gliomas examined, (11)C-4DST PET/CT and (11)C-MET PET/CT detected 20 and 22, respectively. Linear regression analysis between (11)C-4DST and (11)C-MET indicated a weak correlation for SUVmax (r = 0.54, P < 0.008), for T/N ratio (r = 0.56, P < 0.006), and for MTV (r = 0.60, P < 0.003). Linear regression analysis indicated a weak correlation between (11)C-4DST and Ki-67 index for SUVmax (r = 0.46, P < 0.03), for T/N ratio (r = 0.43, P < 0.05), and for MTV (r = 0.68, P < 0.001) and between (11)C-MET MTV and Ki-67 index (r = 0.43, P < 0.04). Using (11)C-4DST, there was a significant difference in SUVmax between grades II and IV (P < 0.03) and in MTV between grades II and IV (P < 0.009) and grades III and IV (P < 0.02). Using (11)C-MET, there was a significant difference in SUVmax (P < 0.009) and T/N ratio (P < 0.02) between grades II and IV and in MTV between grades II and IV (P < 0.03) and grades III and IV (P < 0.02). CONCLUSION: (11)C-4DST PET/CT is feasible for imaging of brain gliomas, as well as (11)C-MET PET/CT. Especially, it showed the highest correlation coefficient between (11)C-4DST MTV and Ki-67 index in newly diagnosed gliomas.

Applicability of emission-based attenuation map for rapid CBF, OEF, and CMRO2 measurements using gaseous (15)O-labeled compounds.

BACKGROUND: Cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) images have facilitated understanding of the pathophysiological basis of cerebrovascular disorders. Such parametric images can be rapidly, measured within around 15 min, using positron emission tomography (PET) with sequentially administered (15)O-labeled oxygen and water. For further shortening, one option is to eliminate the transmission scan by applying an emission-based attenuation correction. METHODS: The validity of the present method was tested by comparing parametric values with emission-based attenuation correction to those with transmission-based correction. This was applied to 27 subjects who were diagnosed with or without cerebrovascular disorders. All subjects received the rapid CBF/OEF/CMRO2 PET measurements. An emission-based attenuation map was generated by estimating the edge of the brain tissue contour on an obtained sinogram and by assuming the uniform tissue coefficient to be 0.1 cm(-1). Then images were reconstructed, and parametric images were computed. RESULTS: No difference was apparent between the emission- and transmission-based methods. Paired t-test showed no significant differences in CBF, OEF, or CMRO2 values between the emission- and transmission-based methods, except in the parietal and occipital and cerebellum and occipital regions, and the differences were less than 10%. The regression analysis showed a close correlation of r = 0.89 to 0.99. CONCLUSIONS: The present study revealed that the attenuation correction can be performed by the emission-based estimation method and clinical PET duration can be shortened for the CBF, OEF, and CMRO2 gas study.

Image accuracy and quality test in rate constant depending on reconstruction algorithms with and without incorporating PSF and TOF in PET imaging.

OBJECTIVE: Positron emission tomography allows imaging of patho-physiological information as a form of rate constants from scanned and reconstructed dynamic image. Some reconstruction algorithms incorporated with time of flight and point spread function have been developed, and quantitative accuracy and quality in the image have been investigated. However, feasibility of the rate constants from the dynamic image has not been directly investigated. We investigated the accuracy and quality in the rate constant by scanning a phantom filled simultaneously with (11)C and (18)F. METHOD: We utilized a phantom filled with (18)F-F(-) solution in the main cylinder and with (11)C-flumazenil solution in seven sub-cylinders. The phantom was scanned by a Biograph mCT and the scanned data were reconstructed with FBP- and OSEM-based algorithms incorporating with and without TOF and/or PSF corrections. Decay rate images as kinetic rate constant were computed for all the reconstructed images and quantitative accuracy and quality in the rate images were investigated. RESULTS: The obtained decay rates were not significantly different from the reference values for both isotopes for all applied algorithms when noise on image was not large. Respective SD was smaller in OSEM with TOF in the (11)C-filled region. CONCLUSION: The present study suggests that OSEM incorporating with TOF provides reasonable quantitative accuracy and image quality regarding decay rates.