Differentiation of suprasellar meningiomas from non-functioning pituitary macroadenomas by 18F-FDG and 13N-Ammonia PET/CT.

BACKGROUND: Differentiation of suprasellar meningiomas (SSMs) from non-functioning pituitary macroadenomas (NFPMAs) is useful for clinical management. We investigated the utility of 13N-ammonia combined with 18F-FDG positron emission tomography (PET)/computed tomography (CT) in distinguishing SSMs from NFPMAs retrospectively. METHODS: Fourteen NFPMA patients and eleven SSM patients with histopathologic diagnosis were included in this study. Every patient underwent both 18F-FDG and 13N-ammonia PET/CT scans. The tumor to gray matter (T/G) ratios were calculated for the evaluation of tumor uptake. RESULTS: The uptake of 18F-FDG was higher in NFPMAs than SSMs, whereas the uptake of 13N-ammonia was obviously lower in NFPMAs than SSMs. The differences of 18F-FDG and 13N-ammonia uptake between the two groups were significant respectively (0.92[0.46] vs 0.59[0.29], P < 0.05, 18F-FDG; 1.58 ± 0.56 vs 2.80 ± 1.45, P < 0.05, 13N-ammonia). Tumor classification demonstrated a high overall accuracy of 96.0% for differential diagnosis. When the two traces were combined, only 1 SSM was misclassified into the NFPMA group. CONCLUSION: SSMs and NFPMAs have different metabolic characteristics on 18F-FDG and 13N-ammonia PET images. The combination of these two tracers can effectively distinguish SSMs from NFPMAs.

Diagnostic accuracy of 13N-ammonia PET, 11C-methionine PET and 18F-fluorodeoxyglucose PET: a comparative study in patients with suspected cerebral glioma.

BACKGROUND: The treatment of patients with glioma depended on the nature of the lesion and on histological grade of the tumor. Positron emission tomography (PET) using 13N-ammonia (NH3), 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) have been used to assess brain tumors. Our aim was to compare their diagnostic accuracies in patients with suspected cerebral glioma. METHODS: Ninety patients with suspicion of glioma based on previous CT/MRI, who underwent NH3 PET, MET PET and FDG PET, were prospectively enrolled in the study. The reference standard was established by histology or clinical and radiological follow-up. Images were interpreted by visual evaluation and semi-quantitative analysis using the lesion-to-normal white matter uptake ratio (L/WM ratio). RESULTS: Finally, 30 high-grade gliomas (HGG), 27 low-grade gliomas (LGG), 10 non-glioma tumors and 23 non-neoplastic lesions (NNL) were diagnosed. On visual evaluation, sensitivity and specificity for differentiating tumors from NNL were 62.7% (42/67) and 95.7% (22/23) for NH3 PET, 94.0% (63/67) and 56.5% (13/23) for MET PET, and 35.8% (24/67) and 65.2% (15/23) for FDG PET. On semi-quantitative analysis, brain tumors showed significantly higher L/WM ratios than NNL both in NH3 and MET PET (both P < 0.001). The sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic (ROC) analysis, respectively, were 64.2, 100% and 0.819 for NH3; and 89.6, 69.6% and 0.840 for MET. Besides, the L/WM ratios of NH3, MET and FDG PET in HGG all significantly higher than that in LGG (all P < 0.001). The predicted (by ROC) accuracy of the tracers (AUC shown in parentheses) were 86.0% (0.896) for NH3, 87.7% (0.928) for MET and 93.0% (0.964) for FDG. While no significant differences in the AUC were seen between them. CONCLUSION: NH3 PET has remarkably high specificity for the differentiation of brain tumors from NNL, but low sensitivity for the detection of LGG. MET PET was found to be highly useful for detection of brain tumors. However, like FDG, high MET uptake is frequently observed in some NNL. NH3, MET and FDG PET all appears to be valuable for evaluating the histological grade of gliomas.

Exploring Coronary Circulatory Response to Stenosis and Its Association With Invasive Physiologic Indexes Using Absolute Myocardial Blood Flow and Coronary Pressure.

BACKGROUND: Although invasive physiological assessment for coronary stenosis has become a standard practice to guide treatment strategy, coronary circulatory response and changes in invasive physiological indexes, according to different anatomic and hemodynamic lesion severity, have not been fully demonstrated in patients with coronary artery disease. METHODS: One hundred fifteen patients with left anterior descending artery stenosis who underwent both 13N-ammonia positron emission tomography and invasive physiological measurement were analyzed. Myocardial blood flow (MBF) measured with positron emission tomography and invasively measured coronary pressures were used to calculate microvascular resistance and stenosis resistance. RESULTS: With progressive worsening of angiographic stenosis severity, both resting and hyperemic transstenotic pressure gradient and stenosis resistance increased (P<0.001 for all) and hyperemic MBF (P<0.001) and resting microvascular resistance (P=0.012) decreased. Resting MBF (P=0.383) and hyperemic microvascular resistance (P=0.431) were not changed and maintained stable. Both fractional flow reserve and instantaneous wave-free ratio decreased as angiographic stenosis severity, stenosis resistance, and transstenotic pressure gradient increased and hyperemic MBF decreased (all P<0.001). When the presence of myocardial ischemia was defined by both low hyperemic MBF and low coronary flow reserve, the diagnostic accuracy of fractional flow reserve and instantaneous wave-free ratio did not differ, regardless of cutoff values of hyperemic MBF and coronary flow reserve. CONCLUSIONS: This study demonstrated how the coronary circulation changes in response to increasing coronary stenosis severity using 13N-ammonium positron emission tomography-derived MBF and invasively measured pressure data. Currently used resting and hyperemic pressure-derived invasive physiological indexes have similar patterns of relationships to the different anatomic and hemodynamic lesion severities. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01366404.

Organ Distribution of 13N Following Intravenous Injection of [13N]Ammonia into Portacaval-Shunted Rats.

Ammonia is neurotoxic, and chronic hyperammonemia is thought to be a major contributing factor to hepatic encephalopathy in patients with liver disease. Portacaval shunting of rats is used as an animal model to study the detrimental metabolic effects of elevated ammonia levels on body tissues, particularly brain and testes that are deleteriously targeted by high blood ammonia. In normal adult rats, the initial uptake of label (expressed as relative concentration) in these organs was relatively low following a bolus intravenous injection of [13N]ammonia compared with lungs, kidneys, liver, and some other organs. The objective of the present study was to determine the distribution of label following intravenous administration of [13N]ammonia among 14 organs in portacaval-shunted rats at 12 weeks after shunt construction. At an early time point (12 s) following administration of [13N]ammonia the relative concentration of label was highest in lung with lower, but still appreciable relative concentrations in kidney and heart. Clearance of 13N from blood and kidney tended to be slower in portacaval-shunted rats versus normal rats during the 2-10 min interval after the injection. At later times post injection, brain and testes tended to have higher-than-normal 13N levels, whereas many other tissues had similar levels in both groups. Thus, reduced removal of ammonia from circulating blood by the liver diverts more ammonia to extrahepatic tissues, including brain and testes, and alters the nitrogen homeostasis in these tissues. These results emphasize the importance of treatment paradigms designed to reduce blood ammonia levels in patients with liver disease.

Effect of acute intravenous beta-blocker administration on myocardial blood flow during same-day hybrid CCTA/PET imaging.

This study aimed to evaluate the impact of acute intravenous beta-blocker administration on myocardial blood flow (MBF) during same-day hybrid coronary computed tomography angiography (CCTA) and 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI). Previous research on the discontinuation of oral beta-blockers before MPI has shown mixed results, with no studies yet exploring the acute intravenous administration in the context of same-day hybrid imaging. This retrospective study included patients with suspected chronic coronary syndromes undergoing same-day hybrid CCTA/13N-ammonia PET MPI. Exclusion criteria comprised coronary artery stenosis ≥ 50% or regional perfusion abnormalities on PET, and baseline oral beta-blocker medication. Intravenous metoprolol (up to 30 mg) was administered as needed for heart rate control before CCTA. MBF measurements were obtained at rest (rMBF) and during stress (sMBF), and myocardial flow reserve (MFR) was calculated. After excluding 281 patients, 154 were eligible for propensity-score matching, resulting in 108 patients divided into two equal groups based on beta-blocker administration. The groups showed no significant differences in baseline characteristics. Among those who received beta-blockers, there was a significant decrease in sMBF (2.21 [IQR 1.72-2.78] versus 2.46 [2.08-2.99] ml∙min-1∙g-1, p = 0.027) and MFR (3.46 [2.70-4.05] versus 3.79 [3.22-4.46], p = 0.030), respectively, compared to those who did not receive beta-blockers. In contrast, rMBF remained unaffected (0.65 [0.54-0.78] versus 0.64 [0.55-0.76] ml∙min-1∙g-1, p = 0.931). Acute intravenous beta-blocker administration significantly impacts MBF, leading to a slight reduction in sMBF and MFR. In contrast, rMBF appears unaffected, suggesting that beta-blockers primarily affect the coronary capacity to respond to vasodilators.

Relationship of blood flow and metabolism to acoustic processing centers of the dolphin brain.

Odontocete brain tissues associated with auditory processing are hypertrophied and modified relative to their terrestrial counterparts. The relationship between the functional demand on these tissues and metabolic substrate requirements is unknown. Using positron emission tomography (PET), relative cerebral blood flow was measured in a bottlenose dolphin. Approximately 60 mCi (13)NH(3) was administered to the dolphin via a catheter inserted into the hepatic vein and threaded proximate to the vena cava. Radiolabel initially appeared as distributed focal points in the cerebellum. Increasing scan time resulted in an increase in the number of focal regions and in the diffusivity of label activity throughout the brain. The time course and spatial distribution of radiolabel was consistent with a cerebral blood supply dominated by the spinal meningeal arteries. Blood flow was predominantly observed in the cerebellum and neocortex, particularly the auditory and visual cortex. Differential brain glucose uptake, previously measured in a separate dolphin, showed good agreement with the differential supply of blood to brain tissues. Rates of blood supply and glucose uptake in the auditory cortex, inferior colliculus, and cerebellum are consistent with a high metabolic demand of tissues which are important to the integration of auditory and other sensory inputs.

Myocardial bridging of the left anterior descending coronary artery is associated with reduced myocardial perfusion reserve: a 13N-ammonia PET study.

Myocardial Bridging (MB) refers to the band of myocardium that abnormally overlies a segment of a coronary artery. This paper quantitatively evaluates the influence of MB of the left anterior descending artery (LAD) on myocardial perfusion of the entire left ventricle. We studied 131 consecutive patients who underwent hybrid rest/stress 13N-ammonia positron emission tomography (PET) and coronary computed tomography angiography (CCTA) due to suspected myocardial ischemia. Patients with previous myocardial infarction and/or significant coronary artery disease (≥ 50% stenosis) were excluded. Myocardial perfusion measurements were compared between patients with and without LAD-MB. Additionally, we evaluated the relationship between anatomical characteristics (length and depth) of LAD-MB and myocardial perfusion measurements. 17 (13%) patients presented a single LAD-MB. Global myocardial perfusion reserve (MPR) was lower in patients with LAD-MB than in patients without LAD-MB (1.9 ± 0.5 vs. 2.3 ± 0.6, p < 0.01). Global stress myocardial blood flow (MBF) was similar in patients with and without LAD-MB (2.2 ± 0.4 vs. 2.3 ± 0.7 ml/g/min, p = 0.40). Global rest MBF was higher in patients with LAD-MB than in patients without LAD-MB (1.2 ± 0.3 vs. 1.0 ± 0.2 ml/g/min, p < 0.01). Global rest MBF, stress MBF, and MPR quantifications were similar in patients with superficial and deep LAD-MB (all p = NS). We did not find any correlation between length and global rest MBF, stress MBF nor MPR (r = - 0.14, p = 0.59; r = 0.44, p = 0.07; and r = 0.45, p = 0.07 respectively). Quantitative myocardial perfusion suggests that LAD-MB may be related to impaired perfusion reserve, an indicator of microvascular dysfunction. Anatomical characteristics of LAD-MB were not related to changes in myocardial perfusion.

Myocardial Microvascular Dysfunction in Rheumatoid ArthritisQuantitation by 13N-Ammonia Positron Emission Tomography/Computed Tomography.

BACKGROUND: The goal of this study was to assess the prevalence of myocardial microvascular dysfunction in rheumatoid arthritis (RA) patients without clinical cardiovascular disease and its association with RA characteristics and measures of cardiac structure and function. METHODS: Participants with RA underwent rest and vasodilator stress N-13 ammonia positron emission tomography and echocardiography. Global myocardial blood flow was quantified at rest and during peak hyperemia. Myocardial flow reserve (MFR) was calculated as peak stress myocardial blood flow/rest myocardial blood flow. A small number of asymptomatic and symptomatic non-RA controls were also evaluated. RESULTS: In RA patients, mean±SD MFR was 2.9±0.8, with 29% having reduced MFR (<2.5). Male sex and higher interleukin-6 were significantly associated with lower MFR, while the use of tumor necrosis factor inhibitors was associated with higher MFR. Lower MFR was associated with higher left ventricle mass index and higher left ventricle volumes but not with ejection fraction or diastolic dysfunction. RA and symptomatic controls had comparable MFR (mean±SD: 2.9±0.8 versus 2.55±0.6; P=0.48). In contrast, MFR was higher in the asymptomatic controls (mean±SD: 3.25±0.7) although not statistically different. CONCLUSIONS: Reduced MFR was observed in a third of RA patients without clinical cardiovascular disease and was associated with a measure of inflammation and with higher left ventricle mass and volumes. MFR in RA patients was similar to controls referred for clinical scans (symptomatic controls). Whether reduced MFR contributes to the increased risk for heart failure in RA remains unknown.

Diagnostic Performance of Resting and Hyperemic Invasive Physiological Indices to Define Myocardial Ischemia: Validation With 13N-Ammonia Positron Emission Tomography.

OBJECTIVES: The authors sought to compare the diagnostic performance of fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), and resting distal coronary artery pressure/aortic pressure (Pd/Pa) using 13N-ammonia positron emission tomography (PET). BACKGROUND: The diagnostic performance of invasive physiological indices was reported to be different according to the reference to define the presence of myocardial ischemia. METHODS: A total of 115 consecutive patients with left anterior descending artery stenosis who underwent both 13N-ammonia PET and invasive physiological measurement were included. Optimal cutoff values and diagnostic performance of FFR, iFR, and resting Pd/Pa were assessed using PET-derived coronary flow reserve (CFR) and relative flow reserve (RFR) as references. To compare discrimination and reclassification ability, each index was compared with integrated discrimination improvement (IDI) and category-free net reclassification index (NRI). RESULTS: All invasive physiological indices correlated with CFR and RFR (all p values <0.001). The overall diagnostic accuracies of FFR, iFR, and resting Pd/Pa were not different for CFR <2.0 (FFR 69.6%, iFR 73.9%, and resting Pd/Pa 70.4%) and RFR <0.75 (FFR 73.9%, iFR 71.3%, and resting Pd/Pa 74.8%). Discrimination and reclassification abilities of invasive physiological indices were comparable for CFR. For RFR, FFR showed better discrimination and reclassification ability than resting indices (IDI = 0.170 and category-free NRI = 0.971 for iFR; IDI = 0.183 and category-free NRI = 1.058 for resting Pd/Pa; all p values <0.001). CONCLUSIONS: The diagnostic performance of invasive physiological indices showed no differences in the prediction of myocardial ischemia defined by CFR. Using RFR as a reference, FFR showed a better discrimination and reclassification ability than resting indices.

Myocardial Blood Flow and Inflammatory Cardiac Sarcoidosis.

OBJECTIVES: This study sought to evaluate the effects of inflammatory sarcoid disease on coronary circulatory function and the response to immune-suppressive treatment. BACKGROUND: Although positron emission tomography assessment of myocardial inflammation is increasingly applied to identify active cardiac sarcoidosis, its effect on coronary flow and immune-suppressive treatment remains to be characterized. METHODS: Thirty-two individuals, who were referred for positron emission tomography/computed tomography, were evaluated for known or suspected cardiac sarcoidosis applying 18F-fluorodeoxyglucose to determine inflammation and 13N-ammonia to assess for perfusion deficits following a high-fat/low-carbohydrate diet and fasting state >12 h to suppress myocardial glucose uptake. Inflammation was quantified with standardized uptake value and regional myocardial blood flow at rest and during regadenoson-stimulated hyperemia was determined in ml/g/min. Positron emission tomography studies were repeated in 18 cases with a median follow-up of 2.5 years (interquartile range [IQR]:1.3 to 3.4 years). RESULTS: Twenty-five exams had normal perfusion but evidence of regional inflammation (group 1), and 21 exams presented a regional perfusion deficit associated with inflammation (group 2). Median myocardial blood flow did not differ between inflamed and noninflamed myocardium in both groups (0.86 ml/g/min [IQR: 0.66 to 1.11 ml/g/min] vs. 0.83 ml/g/min [IQR: 0.64 to 1.12 ml/g/min] and 0.74 ml/g/min [IQR: 0.60 to 0.93 ml/g/min] vs. 0.77 ml/g/min [IQR: 0.59 to 0.95 ml/g/min], respectively). As regards median hyperemic myocardial blood flows, they were significantly lower in the inflamed than in the remote regions in group 1 and 2 (2.31 ml/g/min [IQR: 1.81 to 2.95 ml/g/min] vs. 2.70 ml/g/min [IQR: 2.07 to 3.30 ml/g/min] and 1.61 ml/g/min [IQR: 1.17 to 2.18 ml/g/min] vs. 1.94 ml/g/min [IQR: 1.49 to 2.39 ml/g/min]; p < 0.001, respectively). Immune-suppression-mediated decrease in inflammation was associated with preserved myocardial flow reserve (MFR) at follow-up, whereas MFR significantly worsened in regions without changes or even increases in inflammation (median ΔMFR: 0.07 [IQR: -0.29 to 0.45] vs. -0.24 [IQR: -0.84 to 0.21]; p < 0.001). There was an inverse correlation between pronounced alterations in myocardial inflammation (Δ regional myocardial volume with standardized uptake value >4.1) and ΔMFR (r = -0.47; p = 0.048). CONCLUSIONS: Sarcoid-mediated myocardial inflammation is associated with a regional impairment of coronary circulatory function. The association between immune-suppressive treatment-related alterations in myocardial inflammation and changes in coronary vasodilator capacity suggests direct adverse effect of inflammation on coronary circulatory function in cardiac sarcoidosis.

Integrated Myocardial Perfusion Imaging Diagnostics Improve Detection of Functionally Significant Coronary Artery Stenosis by 13N-ammonia Positron Emission Tomography.

BACKGROUND: Recent evidence suggests that the diagnostic accuracy of myocardial perfusion imaging is improved by quantifying stress myocardial blood flow (MBF) in absolute terms. We evaluated a comprehensive quantitative (13)N-ammonia positron emission tomography ((13)NH3-PET) diagnostic panel, including stress MBF, coronary flow reserve (CFR), and relative flow reserve (RFR) in conjunction with relative perfusion defect (PD) assessments to better detect functionally significant coronary artery stenosis. METHODS AND RESULTS: A total of 130 patients (307 vessels) with coronary artery disease underwent both (13)NH3-PET and invasive coronary angiography with fractional flow reserve (FFR) measurement. Diagnostic accuracy, optimal cut points, and discrimination indices of respective (13)NH3-PET quantitative measures were compared, with FFR as standard reference. The capacity to discern disease with stepwise addition of stress MBF, CFR, and RFR to qualitatively assessed relative PD was also gauged, using the category-free net reclassification index. All quantitative measures showed significant correlation with FFR (PET-derived CFR, r=0.388; stress MBF, r=0.496; and RFR, r=0.780; all P<0.001). Optimal respective cut points for FFR ≤0.8 and ≤0.75 were 1.99 and 1.84 mL/min per g for stress MBF and 2.12 and 2.00 for PET-derived CFR. Discrimination indices of quantitative measures that correlated with FFR ≤0.8 were all significantly higher than that of relative PD (area under the curve: 0.626, 0.730, 0.806, and 0.897 for relative PD, CFR, stress MBF, and RFR, respectively; overall comparison P<0.001). The capacity for functionally significant coronary stenosis was incrementally improved by the successive addition of CFR (net reclassification index=0.629), stress MBF (net reclassification index=0.950), and RFR (net reclassification index=1.253; all P<0.001) to relative PD. CONCLUSIONS: Integrating quantitative (13)NH3-PET measures with qualitative myocardial perfusion assessment provides superior diagnostic accuracy and improves the capacity to detect functionally significant coronary artery stenosis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01621438 and NCT01366404.

Accuracy of cardiac PET imaging using post-injection transmission scan.

UNLABELLED: The purpose of this study was to investigate the accuracy of cardiac PET with post-injection transmission scans. METHODS: We performed a phantom study using 18F solution as well as 13N-ammonia PET study of ten patients. The average activities of no myocardial defect phantom model were estimated, and myocardial defect sizes of 12 phantom models were measured by pre- and post-injection transmission methods at various 18F activities. In 13N-ammonia PET at rest and during adenosine triphosphate (ATP) stress studies, measured defect sizes were compared between both methods. RESULTS: The ratios of average activity estimated by both methods (post/pre value) were almost 1.00 at each 18F activity and segment. Measured defect sizes by both methods showed an excellent correlation with true defect sizes (r = 0.98, p < 0.01 for pre vs. true value: r = 0.98, p < 0.01 for post vs. true value). The mean absolute errors of measurements were minimal up to 3.5% LV, and were similar between both methods. In 13N-ammonia PET, measured defect sizes by both methods also showed a good correlation (r = 0.97, p < 0.01). CONCLUSION: The results indicate that cardiac PET imaging with post-injection transmission scan provides information on myocardial tracer activity as well as myocardial defect size as does conventional pre-injection transmission method.

13N-ammonia combined with 18F-FDG could discriminate between necrotic high-grade gliomas and brain abscess.

PURPOSE: Accurate prediction of brain abscess is beneficial for timely management. In this study, we investigated the utility of 13N-ammonia and its combination with 18F-FDG in differentiating brain abscess from necrotic high-grade gliomas. PATIENTS AND METHODS: Thirteen patients with ring-like enhancement high-grade gliomas and 11 patients with brain abscess were recruited in our study. All of them underwent both 18F-FDG and 13N-ammonia PET imaging. Lesion uptake was evaluated by lesion to normal gray matter ratio (L/N). Histopathology diagnosis was obtained for all the patients after PET imaging. RESULTS: The L/N values of 18F-FDG were not significantly different between brain abscess and necrotic high-grade gliomas (P = 0.35). The uptake of 13N-ammonia in gliomas was higher than that in abscess lesions (L/N: 1.38 ± 0.31 vs 0.84 ± 0.18, P < 0.001). The receiver operating characteristic curve analysis determined the optimal L/N cutoff value (13N-ammonia) of 1.0 with the area under the curve of 0.94 and the overall accuracy of 87.5%. Discriminant analysis demonstrated that the combination of 18F-FDG and 13N-ammonia could distinguish the 2 clinical entities with higher accuracy of 95%, and only 1 necrotic glioma lesion was misclassified into the abscess group. CONCLUSIONS: 13N-ammonia is effective in distinguishing brain abscess from necrotic high-grade gliomas, and its combination with 18F-FDG could further elevate the diagnostic accuracy.

Imaging of the human heart after administration of L-(N-13)glutamate.

In normal volunteers and cancer patients, studies using L-(N-13)glutamate as an imaging agent showed localization of N-13 activity in the heart. Other organs that were well visualized include the liver, pancreas, and salivary glands. In ten subjects the average myocardial uptake after intravenous injection of labeled glutamate was (5.7 +/- 0.39)% (s.e.m.) of injected dose, as determined by a quantitative scanning system. The concentration of N-13 activity in the human heart could not be predicted from previous studies involving myocardial uptake in dogs and rodents after administration of L-(N-13)glutamate.

Advantages of short-lived positron-emitting radioisotopes for intracoronary radiation therapy with liquid-filled balloons to prevent restenosis.

UNLABELLED: Balloon catheters filled with liquid radioisotopes provide excellent dose homogeneity for intracoronary radiation therapy but are associated with risk for rupture or leakage. We hypothesized that the safety of liquid-filled balloons may be improved once positron emitters with half-lives below 2 h are used instead of the high-energy beta-emitters 166Ho, 186Re, or 188Re, all of which have a longer half-life of at least 17 h. METHODS: To support this concept, the suitability of 18F (half-life, 109.8 min), 68Ga (half-life, 67.6 min), 11C (half-life, 20.4 min), 13N (half-life, 9.97 min), and 15O (half-life, 2.04 min) for intracoronary radiation therapy was evaluated. Potential tissue penetration of positron radiation was assessed in a series of phantom experiments using Gafchromic film. Antiproliferative efficacy of positrons emitted by 68Ga was investigated in vitro using cultured bovine aortic smooth muscle cells (BASMCs), and was compared with gamma-radiation emitted by 137Cs. To characterize the remaining risk, we estimated radiotoxicity after accidental intravascular balloon rupture on the basis of tabulated isotope-specific doses (ICRP 53) and compared these values with 188Re. RESULTS: Half-dose depth of tissue penetration measured in phantom experiments was 0.29 mm for 18F, 0.42 mm for 11C, 0.54 mm for 13N, 0.79 mm for 15O, and 0.9 mm for 68Ga. Irradiation of cultured BASMCs with positron radiation (68Ga) induced dose-dependent inhibition of proliferation with complete proliferative arrest at doses exceeding 6 Gy. ED(50) and ED(80) were 2.5 +/- 0.4 Gy (mean +/- SD) and 4.4 +/- 0.8 Gy, respectively. Antiproliferative efficacy was equal to that of the 662-keV gamma-radiation emitted by 137Cs (ED(50), 3.8 +/- 0.2 Gy; ED(80), 8.0 +/- 0.3 Gy). Estimates made for patient whole-body and organ doses were generally below 50 mSv/1.85 GBq for all investigated positron emitters. The same dose estimates for 188Re were 6-20 fold higher. CONCLUSION: Among the studied radioisotopes, 68Ga is the most attractive source for liquid-filled balloons because of its convenient half-life, sufficient positron energy (2.92 MeV), documented antiproliferative efficacy, and uncomplicated availability from a radioisotope generator. The safety profile for 68Ga is significantly better than that of 188Re, which suggests this radioisotope should be evaluated further in preclinical studies.

Effects of surfactant depletion on regional pulmonary metabolic activity during mechanical ventilation.

Inflammation during mechanical ventilation is thought to depend on regional mechanical stress. This can be produced by concentration of stresses and cyclic recruitment in low-aeration dependent lung. Positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) allows for noninvasive assessment of regional metabolic activity, an index of neutrophilic inflammation. We tested the hypothesis that, during mechanical ventilation, surfactant-depleted low-aeration lung regions present increased regional (18)F-FDG uptake suggestive of in vivo increased regional metabolic activity and inflammation. Sheep underwent unilateral saline lung lavage and were ventilated supine for 4 h (positive end-expiratory pressure = 10 cmH(2)O, tidal volume adjusted to plateau pressure = 30 cmH(2)O). We used PET scans of injected (13)N-nitrogen to compute regional perfusion and ventilation and injected (18)F-FDG to calculate (18)F-FDG uptake rate. Regional aeration was quantified with transmission scans. Whole lung (18)F-FDG uptake was approximately two times higher in lavaged than in nonlavaged lungs (2.9 ± 0.6 vs. 1.5 ± 0.3 10(-3)/min; P < 0.05). The increased (18)F-FDG uptake was topographically heterogeneous and highest in dependent low-aeration regions (gas fraction 10-50%, P < 0.001), even after correction for lung density and wet-to-dry lung ratios. (18)F-FDG uptake in low-aeration regions of lavaged lungs was higher than that in low-aeration regions of nonlavaged lungs (P < 0.05). This occurred despite lower perfusion and ventilation to dependent regions in lavaged than nonlavaged lungs (P < 0.001). In contrast, (18)F-FDG uptake in normally aerated regions was low and similar between lungs. Surfactant depletion produces increased and heterogeneously distributed pulmonary (18)F-FDG uptake after 4 h of supine mechanical ventilation. Metabolic activity is highest in poorly aerated dependent regions, suggesting local increased inflammation.

Measurement of regional specific lung volume change using respiratory-gated PET of inhaled 13N-nitrogen.

UNLABELLED: Regional specific lung volume change (sVol), defined as the regional tidal volume divided by the regional end-expiratory gas volume, is a key variable in lung mechanics and in the pathogenesis of ventilator-induced lung injury. Despite the usefulness of PET to study regional lung function, there is no established method to assess sVol with PET. We present a method to measure sVol from respiratory-gated PET images of inhaled (13)N-nitrogen ((13)NN), validate the method against regional specific ventilation (sV), and study the effect of region-of-interest (ROI) volume and orientation on the sVol-sV relationship. METHODS: Four supine sheep were mechanically ventilated (tidal volume V(T) = 8 mL/kg, respiratory rate adjusted to normocapnia) at low (n = 2, positive end-expiratory pressure = 0) and high (n = 2, positive end-expiratory pressure adjusted to achieve a plateau pressure of 30 cm H(2)O) lung volumes. Respiratory-gated PET scans were obtained after inhaled (13)NN equilibration both at baseline and after a period of mechanical ventilation. We calculated sVol from (13)NN-derived regional fractional gas content at end-inspiration (F(EI)) and end-expiration (F(EE)) using the formula sVol = (F(EI) - F(EE))/(F(EE)[1 - F(EI)]). sV was computed as the inverse of the subsequent (13)NN washout curve time constant. ROIs were defined by dividing the lung field with equally spaced coronal, sagittal, and transverse planes, perpendicular to the ventrodorsal, laterolateral, and cephalocaudal axes, respectively. RESULTS: sVol-sV linear regressions for ROIs based on the ventrodorsal axis yielded the highest R(2) (range, 0.71-0.92 for mean ROI volumes from 7 to 162 mL), the cephalocaudal axis the next highest (R(2) = 0.77-0.88 for mean ROI volumes from 38 to 162 mL), and the laterolateral axis the lowest (R(2) = 0.65-0.83 for mean ROI volumes from 8 to 162 mL). ROIs based on the ventrodorsal axis yielded lower standard errors of estimates of sVol from sV than those based on the laterolateral axis or the cephalocaudal axis. CONCLUSION: sVol can be computed with PET using the proposed method and is highly correlated with sV. Errors in sVol are smaller for larger ROIs and for orientations based on the ventrodorsal axis.

Electrocardiographic gating in positron emission computed tomography.

Electrocardiographic (ECG) synchronized multiple gated data acquisition was employed with positron emission computed tomography (ECT) to obtain images of myocardial blood pool and myocardium. The feasibility and requirements of multiple gated data acquisition in positron ECT were investigated for 13NH3, (18F)-2-fluoro-2-D-deoxyglucose, and (11C)-carboxyhemoglobin. Examples are shown in which image detail is enhanced and image interpretation is facilitated when ECG gating is employed in the data collection. Analysis of count rate data from a series of volunteers indicates that multiple, statistically adequate images can be obtained under a multiple gated data collection format without an increase in administered dose.

Recovery of (15)n in the body, urine, and gas phase of piglets infused intravenously with (15)n L-alanine from 12-72 hours of age.

Previous studies of nitrogen metabolism provided evidence suggesting that nitrogen excretory product(s) not measured by standard methods of analysis escape detection. To determine whether (15)N could be recovered quantitatively in the body, urine, or expired gas, newborn piglets (n = 16; 1.47 +/- 0.27 kg) were infused intravenously with (15)N L-alanine from 12 to 72 h of age at a rate providing 25% of the piglets' resting energy expenditure and a (15)N abundance of 2.3 (n = 4), 2.8 (n = 10), or 3.3 (n = 2) atom percent. To investigate the possibility of gaseous nitrogen excretion, 4 piglets infused with (15)N L-alanine were housed in a closed circuit respiration system initially flushed with an 80% argon:20% O(2) mixture. The gas composition of the system was monitored at 12-h intervals throughout the experiment. Mean total recovery of (15)N was 93.3 +/- 2.8% and was significantly different from 100% (P < 0.001). To determine whether (15)N recovery was altered by metabolism, 2 piglets (1.34 +/- 0.13 kg) were killed 6 min after a bolus i.v. infusion of (15)N L-alanine (97.96 +/- 1.13 atom percent). Mean recovery of (15)N in the bodies of these piglets was 101.5 +/- 1.6% and was not different from 100%. No change in chamber gas (28)N(2) (P = 0.0969) or (29)N(2) (P = 0.08565) over 72 h was evident. The inability to recover 6.7 +/- 2.8% of infused (15)N suggests that a nitrogen-containing excretory product or metabolite may be escaping detection, but the discrepancy cannot be explained by gaseous nitrogen ((28)N(2), (29)N(2), or (30)N(2)) excretion.