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.

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.

Myocardial blood flow and its transit time, oxygen utilization, and efficiency of highly endurance-trained human heart.

Highly endurance-trained athlete's heart represents the most extreme form of cardiac adaptation to physical stress, but its circulatory alterations remain obscure. In the present study, myocardial blood flow (MBF), blood mean transit time (MTT), oxygen extraction fraction (OEF) and consumption (MVO2), and efficiency of cardiac work were quantified in highly trained male endurance athletes and control subjects at rest and during supine cycling exercise using [(15)O]-labeled radiotracers and positron emission tomography. Heart rate and MBF were lower in athletes both at rest and during exercise. OEF increased in response to exercise in both groups, but was higher in athletes (70 ± 21 vs. 63 ± 11 % at rest and 86 ± 13 vs. 73 ± 10 % during exercise). MTT was longer and vascular resistance higher in athletes both at rest and during exercise, but arterial content of 2,3-diphosphoglycerate (oxygen affinity) was unchanged. MVO2 per gram of myocardium trended (p = 0.08) lower in athletes both at rest and during exercise, while myocardial efficiency of work and MVO2 per beat were not different between groups. Arterial levels of free fatty acids were ~twofold higher in athletes likely leading to higher myocardial fatty acid oxidation and hence oxygen cost, which may have blunted the bradycardia-induced decrease in MVO2. Finally, the observed group differences in MBF, OEF, MTT and vascular resistance remained significant also after they were controlled for differences in MVO2. In conclusion, in highly endurance-trained human heart, increased myocardial blood transition time enables higher oxygen extraction levels with a lower myocardial blood flow and higher vascular resistance. These physiological adaptations to exercise training occur independently of the level of oxygen consumption and together with training-induced bradycardia may serve as mechanisms to increase functional reserve of the human heart.

Cerebral blood flow and oxygen metabolism measurements using positron emission tomography on the first day after carotid artery stenting.

BACKGROUND: The aim of the present study is the characterization of hemodynamics to predict hyperperfusion syndrome (HPS) after carotid artery stenting (CAS) with positron emission tomography (PET) obtained before and on the first day after the treatment. METHODS: Cerebral perfusion and oxygen metabolism were evaluated by (15)O-gas PET in 18 patients with symptomatic internal carotid artery (ICA) stenosis before and on the first day after CAS. Regional cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO2), and cerebral blood volume (CBV) were measured in the ipsilateral and contralateral middle cerebral artery territories and compared between before and after CAS. RESULTS: CBF increased in 16 of 18 patients on the first day after CAS and postoperative CBF was significantly higher than preoperative CBF bilaterally. OEF decreased in 15 of 18 patients on the first day after CAS and postoperative OEF was significantly lower than preoperative OEF in the ipsilateral hemisphere. CMRO2 and CBV did not change significantly. None of the patients showed HPS after CAS. All patients who had preoperative OEF of 53% or more (misery perfusion) in the ipsilateral hemisphere showed 50% or more increase in CBF postoperatively. The preoperative OEF value significantly correlated with the rate of postoperative increase in CBF bilaterally. CONCLUSIONS: CAS increases cerebral perfusion and improves hemodynamic compromise in patients with symptomatic ICA stenosis. Although we could not clarify the usefulness of PET before and on the first day after CAS in predicting HPS, a high preoperative OEF is related to postoperative marked CBF increase and might be used as a predictor of HPS. Patients with greater hemodynamic compromise with a high preoperative OEF should be managed carefully to prevent HPS, but they have a greater chance of CBF increase after CAS.

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.

Evaluation of 3'-deoxy-3'-[18F]-fluorothymidine (18F-FLT) kinetics correlated with thymidine kinase-1 expression and cell proliferation in newly diagnosed gliomas.

PURPOSE: The thymidine analog 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) has been developed as a positron emission tomography (PET) tracer to assess the proliferation activity of tumors in vivo. The present study investigated the relationship between the kinetic parameters of (18)F-FLT in vivo and thymidine kinase-1 (TK-1) expression and cell proliferation rate in vitro, and blood-brain barrier (BBB) breakdown in human brain gliomas. METHODS: A total of 21 patients with newly diagnosed gliomas were examined by (18)F-FLT PET kinetic analysis. Maximum standardized uptake value (SUVmax) and tumor-to-normal (T/N) ratio of (18)F-FLT in the tumor and (18)F-FLT kinetic parameters in the corresponding contralateral region were determined. The expression levels of TK-1 protein and mRNA were determined by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR), respectively, using surgical specimens. The cell proliferation rate of the tumor was determined in terms of the Ki-67 labeling index. BBB breakdown was evaluated on MR images with contrast enhancement. RESULTS: (18)F-FLT SUVmax and T/N ratio were significantly correlated with the influx rate constant (K (1); P = 0.001 and P < 0.001, respectively), but not with the phosphorylation rate constant (k (3)). IHC and real-time PCR studies demonstrated a significant correlation between K (1) and TK-1 mRNA expression (P = 0.001), but not between k (3) and TK-1 protein and mRNA expression. Linear regression analysis revealed a significant correlation between K (1) and the Ki-67 index (P = 0.003), but not between k (3) and the Ki-67 index. TK-1 mRNA expression was significantly correlated with the Ki-67 index (P = 0.009). (18)F-FLT SUVmax and T/N ratio were significantly correlated with BBB breakdown evaluated by contrast enhancement in MR images (P = 0.003 and P = 0.011, respectively). CONCLUSION: These results indicate that (18)F-FLT uptake in the tumor is significantly related to transport through the disrupted BBB, but not through phosphorylation activity. Although the tissue TK-1 expression reflects tumor proliferation activity, the phosphorylation rate constant k (3) determined by (18)F-FLT PET kinetic analysis does not accurately reflect TK-1 expression in the tissue and should not be used as a surrogate biomarker of cell proliferation activity in human brain gliomas.

Detection of brain amyloid ß deposition in patients with neuropsychological impairment after traumatic brain injury: PET evaluation using Pittsburgh Compound-B.

OBJECTIVE: Traumatic brain injury (TBI) is an epigenetic risk factor for Alzheimer's disease (AD) and amyloid ß (Aß) deposition is observed histopathologically in the traumatized brain. This study was conducted to detect cerebral Aß deposition using amyloid positron emission tomography (PET) in patients with neuropsychological impairment after TBI. METHODS: Twelve patients with post-traumatic neuropsychological impairment (11 men and one woman, age range = 21-78 years) were examined using Pittsburgh Compound B ((11)C-PIB) PET at the chronic stage after TBI (range = 5-129 months). RESULTS: (11)C-PIB was positive in three patients and negative in the other nine patients. There was no correlation between (11)C-PIB deposition and the severity of injury; initial CT findings; elapsed time from the injury; and neuropsychological test scores. CONCLUSIONS: The absence of Aß deposition in many patients with chronic neuropsychological impairment after TBI does not support the premise that Aß pathology progresses over time in the traumatized brain. Early and sequential (11)C-PIB PET examination may clarify the time course of Aß deposition in the traumatized brain and the relationship between traumatic brain insult and subsequent neuropsychological impairment.

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.

Correlation of biological aggressiveness assessed by 11C-methionine PET and hypoxic burden assessed by 18F-fluoromisonidazole PET in newly diagnosed glioblastoma.

PURPOSE: Glioblastoma multiforme (GBM) is characterized by tissue hypoxia associated with resistance to radiotherapy and chemotherapy. To clarify the biological link between hypoxia and tumour-induced neovascularization and tumour aggressiveness, we analysed detailed volumetric and spatial information of viable hypoxic tissue assessed by (18)F-fluoromisonidazole (FMISO) PET relative to neovascularization in Gd-enhanced MRI and tumour aggressiveness by L-methyl-(11)C-methionine (MET) PET in newly diagnosed GBMs. METHODS: Ten patients with newly diagnosed GBMs were investigated with FMISO PET, MET PET and Gd-enhanced MRI before surgery. Tumour volumes were calculated by performing a three-dimensional threshold-based volume of interest (VOI) analysis for metabolically active volume on MET PET (MET uptake indices of ≥1.3 and ≥1.5) and Gd-enhanced volume on MRI. FMISO PET was scaled to the blood FMISO activity to create tumour to blood (T/B) images. The hypoxic volume (HV) was defined as the region with T/B greater than 1.2. PET and MR images of each patient were coregistered to analyse the spatial location of viable hypoxic tissue relative to neovascularization and active tumour extension. RESULTS: Metabolically active tumour volumes defined using MET uptake indices of ≥1.3 and ≥1.5 and the volumes of Gd enhancement showed a strong correlation (r = 0.86, p < 0.01 for an index of ≥1.3 and r = 0.77, p < 0.05 for an index of ≥1.5). The HVs were also excellently correlated with the volumes of Gd enhancement (r = 0.94, p < 0.01). The metabolically active tumour volumes as defined by a MET uptake index of ≥1.3 and the HVs exhibited a strong correlation (r = 0.87, p < 0.01). On superimposed images, the metabolically active area on MET PET defined by a MET uptake index of ≥1.3 was usually larger than the area of the Gd enhancement and about 20-30% of the MET area extended outside the area of the enhancement. On the other hand, the surface area of viable hypoxic tissue with a T/B cutoff of ≥1.2 on FMISO PET did not substantially differ from the area of the Gd enhancement. CONCLUSION: The volumetric analysis demonstrates that the viable hypoxic tissue assessed by FMISO PET is related to the neovascularization in Gd-enhanced MRI and the tumour aggressiveness by MET PET in newly diagnosed GBMs. The spatial analysis shows that the metabolically active tumour may be substantially underestimated by Gd-enhanced MRI. Complementary use of MET and FMISO to Gd-enhanced MRI may improve the understanding of tumour biology and lead to the most efficient delineation of tumour volume and treatment strategy.

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.

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.

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.

Quantification of regional myocardial oxygen metabolism in normal pigs using positron emission tomography with injectable (15)O-O (2).

PURPOSE: Although (15)O-O(2) gas inhalation can provide a reliable and accurate myocardial metabolic rate for oxygen by PET, the spillover from gas volume in the lung distorts the images. Recently, we developed an injectable method in which blood takes up (15)O-O(2) from an artificial lung, and this made it possible to estimate oxygen metabolism without the inhalation protocol. In the present study, we evaluated the effectiveness of the injectable (15)O-O(2) system in porcine hearts. METHODS: PET scans were performed after bolus injection and continuous infusion of injectable (15)O-O(2) via a shunt between the femoral artery and the vein in normal pigs. The injection method was compared to the inhalation method. The oxygen extraction fraction (OEF) in the lateral walls of the heart was calculated by a compartmental model in view of the spillover and partial volume effect. RESULTS: A significant decrease of lung radioactivity in PET images was observed compared to the continuous inhalation of (15)O-O(2) gas. Furthermore, the injectable (15)O-O(2) system provides a measurement of OEF in lateral walls of the heart that is similar to the continuous-inhalation method (0.71 +/- 0.036 and 0.72 +/- 0.020 for the bolus-injection and continuous-infusion methods, respectively). CONCLUSION: These results indicate that injectable (15)O-O(2) has the potential to evaluate myocardial oxygen metabolism.

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.

Non-invasive diagnosis of acute mesenteric ischaemia using PET.

PURPOSE: Acute mesenteric ischaemia (AMI) is a lethal disease with an increasing incidence. Despite the availability of effective treatment, AMI remains a vascular emergency with over 60% mortality rate mainly due to late diagnosis. The difficulty in diagnosing this fatal condition stems from non-specific clinical and laboratory findings and lack of appropriate imaging study. Our aim was to test a non-invasive method of identifying AMI using PET. METHODS: The study was conducted in normal pigs (n = 14), sham-operated pigs (n = 4) and pigs undergoing ischaemia and reperfusion of intestine (n = 6). Liver blood flow was imaged by H(2) (15)O PET and liver blood content by C(15)O PET. Both scans were performed during intestinal ischaemia and during reperfusion. RESULTS: AMI was identified by PET imaging of hepatic perfusion and blood pool. The H(2) (15)O PET scan during AMI detected a 40% decrease in total liver perfusion, which was caused by a 45% reduction of portal blood flow and no alteration in arterial blood flow. Compromised hepatic perfusion during AMI was accompanied by a 75% decrease in hepatic blood pool recognized by the C(15)O PET scan. The striking reduction of liver blood flow and blood content persisted during reperfusion of intestine. CONCLUSION: Our results demonstrate that AMI can be readily recognized by PET imaging of liver blood flow and blood content. Moreover, PET can be used in detection of perfusion abnormalities after revascularization. This non-invasive imaging tool could represent a novel approach to diagnose AMI.

Parametric renal blood flow imaging using [15O]H2O and PET.

PURPOSE: The quantitative assessment of renal blood flow (RBF) may help to understand the physiological basis of kidney function and allow an evaluation of pathophysiological events leading to vascular damage, such as renal arterial stenosis and chronic allograft nephropathy. The RBF may be quantified using PET with H(2)(15)O, although RBF studies that have been performed without theoretical evaluation have assumed the partition coefficient of water (p, ml/g) to be uniform over the whole region of renal tissue, and/or radioactivity from the vascular space (V(A). ml/ml) to be negligible. The aim of this study was to develop a method for calculating parametric images of RBF (K(1), k(2)) as well as V(A) without fixing the partition coefficient by the basis function method (BFM). METHODS: The feasibility was tested in healthy subjects. A simulation study was performed to evaluate error sensitivities for possible error sources. RESULTS: The experimental study showed that the quantitative accuracy of the present method was consistent with nonlinear least-squares fitting, i.e. K(1,BFM)=0.93K(1,NLF)-0.11 ml/min/g (r=0.80, p<0.001), k(2,BFM)=0.96k(2,NLF)-0.13 ml/min/g (r=0.77, p<0.001), and V(A,BFM)=0.92V(A,NLF)-0.00 ml/ml (r=0.97, p<0.001). Values of the Akaike information criterion from this fitting were the smallest for all subjects except two. The quality of parametric images obtained was acceptable. CONCLUSION: The simulation study suggested that delay and dispersion time constants should be estimated within an accuracy of 2 s. V(A) and p cannot be neglected or fixed, and reliable measurement of even relative RBF values requires that V(A) is fitted. This study showed the feasibility of measurement of RBF using PET with H(2)(15)O.

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.

Optimal scan time of oxygen-15-labeled gas inhalation autoradiographic method for measurement of cerebral oxygen extraction fraction and cerebral oxygen metabolic rate.

OBJECTIVE: Regional cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) can be estimated from C15O, H(2)15O, and 15O2 tracers and positron emission tomography (PET) using an autoradiographic (ARG) method. Our objective in this study was to optimize the scan time for 15O2 gas study for accurate estimation of OEF and CMRO2. METHODS: We evaluated statistical noise in OEF by varying the scan time and error caused by the tissue heterogeneity in estimated OEF and CMRO2 using computer simulations. The characteristics of statistical noise were investigated by signal-to-noise (S/N) ratio from repeated tissue time activity curves with noise, which were generated using measured averaged arterial input function and assuming CBF=20, 50, and 80 (ml/100 g per minute). Error caused by tissue heterogeneity was also investigated by estimated OEF and CMRO2 from tissue time activity curve with mixture of gray and white matter varying fraction of mixture. In the simulations, three conditions were assumed (i) CBF in gray and white matter (CBFg and CBFw) was 80 and 20, OEF in gray and white matter (Eg and Ew) was 0.4 and 0.3, (ii) CBFg and CBFw decreased by 50%, and Eg and Ew increased by 50% when compared with conditions (i) and (iii). CBFg and CBFw decreased by 80%, and Eg and Ew increased by 50% when compared with condition (i). RESULTS: The longer scan time produced the better S/N ratio of estimated OEF value from three CBF values (20, 50, and 80). Errors of estimated OEF for three conditions owing to tissue heterogeneity decreased, as scan time took longer. Meanwhile in the case of CMRO2, 3 min of scan time was desirable. CONCLUSIONS: The optimal scan time of 15O2 inhalation study with the ARG method was concluded to be 3 min from taking into account for maintaining the S/N ratio and the quantification of accurate OEF and CMRO2.

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.