Evaluation of Coronary Circulation by 13N-Ammonia Myocardial Perfusion Positron Emission Tomography in Patients with Right Coronary Artery Occlusion Due to Kawasaki Disease.

BACKGROUND: Although occlusion of the right coronary artery (RCA) is common in the remote stages of Kawasaki disease, revascularization of the RCA is challenging in children and is usually managed by observation without intervention. METHODS: Using adenosine-stress 13N-ammonia myocardial perfusion positron emission tomography, we evaluated coronary circulation in 14 patients (12 males) with RCA occlusion to identify ischemia (myocardial flow ratio < 2.0) in the RCA region and examined hemodynamics, cardiac function, and coronary aneurysm diameter. These variables were also compared in patients with/without RCA segmental stenosis (SS). RESULTS: There were five cases of ischemia in the RCA region. RCA myocardial blood flow (MBF) at rest was higher in patients with ischemia than in those without ischemia, but the difference was not significant (1.27 ± 0.21 vs. 0.82 ± 0.16 mL/min/g, p = 0.2053). Nine patients presented with RCA SS, and age at onset of Kawasaki disease tended to be lower in those with SS. The maximum aneurysm diameter of RCA was significantly smaller in patients with SS (10.0 ± 2.8 vs. 14.7 ± 1.6, p = 0.0239). No significant differences in other variables were observed between patients with/without ischemia and SS. CONCLUSIONS: At rest, MBF in the RCA region was relatively well preserved, even in patients with RCA occlusion, and there was no progressive deterioration in cardiac function. Adenosine stress showed microcirculatory disturbances in only half of the patients, indicating that it is reversible in children with Kawasaki disease.

Risk Stratification Using Right Ventricular Longitudinal Strain Ratio Derived from 13N-Ammonia PET in Patients with Ischemic Heart Disease.

Purpose To investigate whether right ventricular (RV) myocardial strain ratio (RVMSR) assessed using nitrogen 13 ammonia (13N-NH3) PET can predict cardiovascular events in patients with ischemic heart disease (IHD). Materials and Methods This retrospective study included 480 consecutive patients (mean age, 66 years ± 12 [SD]; 334 males and 146 females) with IHD who underwent 13N-NH3 PET. RVMSR was defined as the ratio of RV strain during stress to that at rest. The primary end point was major adverse cardiac events (MACEs), defined as cardiac death or heart failure hospitalization. The ability of RVMSR to predict MACE was assessed using receiver operating characteristic (ROC) curve and Kaplan-Meier analyses. Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) with 95% CIs. Results ROC curve analysis identified a sensitivity and specificity of 84% and 82%, respectively, for predicting MACE from RVMSR. Patients with reduced RVMSR (<110.2) displayed a significantly higher rate of MACE than those with a preserved RVMSR (34 of 240 vs four of 240; P < .001). Cox proportional hazards regression analysis of imaging parameters, including myocardial flow reserve, indicated that RVMSR was an independent predictor of MACE (HR, 0.94 [95% CI: 0.92, 0.97]; P < .001). Conclusion RVMSR was an independent predictor of MACE and has potential to aid in the risk stratification of patients with IHD. Keywords: Right Ventricular Myocardial Strain Ratio, Myocardial Flow Reserve, Ischemic Heart Disease, 13N-Ammonia Positron Emission Tomography Supplemental material is available for this article. © RSNA, 2024.

Left ventricular shape index and eccentricity index with ECG-gated Nitrogen-13 ammonia PET/CT in patients with myocardial infarction, ischemia, and normal perfusion.

BACKGROUND: LV geometry with shape index (SI) and eccentricity index (EI) measured by myocardial perfusion positron emission tomography/computed tomography (PET/CT) may allow the evaluation of left ventricular (LV) adverse remodeling. This first study aims to explore the relationship of SI and EI values acquired by Nitrogen-13 ammonia PET/CT in patients with normal perfusion, ischemia, and myocardial infarction. And evaluate the correlations between the variables of LV geometry, and with the variables of LV function. METHODS AND RESULTS: One hundred and forty patients who underwent an electrocardiogram (ECG)-gated PET/CT were selected and classified into 4 groups according to ischemia or infarction burden (normal perfusion, mild ischemia, moderate-severe ischemia, and infarction). The variables were automatically retrieved using dedicated software (QPS/QGS; Cedars-Sinai, Los Angeles, CA, USA). On multicomparison analysis (one-way ANOVA and Dunnett's Test), subjects in the infarction group had significant higher values of SI end-diastolic rest (P < 0.001), and stress (P = 0.003), SI end-systolic rest (P = 0.002) and stress (P < 0.001) as well as statistically significant lower values of EI rest (P < 0.001) and stress (P < 0.001) when compared with all other groups. Regarding Pearson correlation, in the infarcted group all the variables of SI and EI were significantly correlated (P < 0.001) with strong correlation coefficients (>0.60). SI end-systolic correlated significantly with the variables of LV function independently of the group of patients (P < 0.05). CONCLUSIONS: Shape and eccentricity indices differ in patients with myocardial infarction as compared to patients with ischemia or normal perfusion. This encourage further research in their potential for detecting LV adverse remodeling.

A novel method for tracking nitrogen kinetics in vivo under hyperbaric conditions using radioactive nitrogen-13 gas and positron emission tomography.

Decompression sickness (DCS) is caused by gaseous nitrogen dissolved in tissues forming bubbles during decompression. To date, no method exists to identify nitrogen within tissues, but with advances in positron-emission tomography (PET) technology, it may be possible to track gaseous radionuclides into tissues. We aimed to develop a method to track nitrogen movement in vivo and under hyperbaric pressure that could then be used to further our understanding of DCS using nitrogen-13 (13N2). A single anesthetized female Sprague-Dawley rat was exposed to 625 kPa, composed of air, isoflurane, and 13N2 for 10 min. The PET scanner recorded 13N2 during the hyperbaric exposure with energy windows of 250-750 keV. The PET showed an increase in 13N2 concentration in the lung, heart, and abdominal regions, which all reached a plateau after ∼4 min. This showed that it is possible to gain noninvasive in vivo measurements of nitrogen kinetics through the body while at hyperbaric pressures. Tissue samples showed radioactivity above background levels in the blood, brain, liver, femur, and thigh muscle when assessed using a γ counter. The method can be used to evaluate an array of challenges to our understanding of decompression physiology by quantifying nitrogen load through γ counts of 13N2, and signal intensity of the PET. Further development of the method will improve the specificity of the measured outcomes, and enable it to be used with larger mammals, including humans.NEW & NOTEWORTHY This article describes a method for the in vivo quantification and tracking of nitrogen through the mammalian body whilst exposed to hyperbaric pressure. The method has the potential to further our understanding of decompression sickness, and quantitatively evaluate the effectiveness of both the treatment and prevention of decompression sickness.

Protocolo de un día para la PET/TC con 18F-FDG y 13N-amonio con escala de desacoplamiento de la captación para diferenciar el glioma de bajo grado no tratado de la inflamación / One-day protocol for 18F-FDG and 13N-ammonia PET/CT with uptake decoupling score in differentiating untreated low-grade glioma from inflammation

PROPÓSITO: La identificación precisa de los gliomas de bajo grado (GBG; grados I y II de la Organización Mundial de la Salud) y su diferenciación de las lesiones por inflamación cerebral (BIL) sigue siendo difícil; sin embargo, es esencial para el tratamiento. Este estudio evaluó si un protocolo de un día para la PET/TC con 18F-FDG y 13N-amonio con análisis de desacoplamiento de la captación podría diferenciar los GBG de las BIL. MATERIALES Y MÉTODOS: Veintiocho pacientes con GBG y 16 pacientes con BIL se sometieron a PET/TC con 18F-FDG y 13N-amonio el mismo día antes de cualquier tipo de terapia. La puntuación de desacoplamiento y la relación tumor/tejido normal (T/N) de 18F-FDG y 13N-amonio se calcularon en cada localización. Se utilizó la prueba t de Student para comparar valores, y el análisis de la curva ROC para establecer un valor de corte para la relación T/N y la puntuación de desacoplamiento. Se calculó el área bajo la curva (AUC) para evaluar la eficacia diferencial. RESULTADOS: Se observaron diferencias significativas en la relación T/N de 13N-amonio (p = 0,018) y en la puntuación de desacoplamiento (p = 0,003) entre los GBG y las BIL; sin embargo, la relación T/N de 18F-FDG no mostró ninguna diferencia (p = 0,413). Los valores de corte óptimos para la relación T/N de 18F-FDG, la relación T/N de 13N-amonio y la puntuación de desacoplamiento fueron 0,73, 0,97 y 2,31, respectivamente, con AUC correspondientes de 0,48, 0,68 y 0,77. Los respectivos parámetros de sensibilidad, especificidad y precisión que utilizan estos valores de corte fueron 53,6%, 62,5% y 56,8%, respectivamente, para 18F-FDG; 50,0%, 75,0% y 59,1%, respectivamente, para 13N-amonio; y 60,7%, 93,8% y 72,7%, respectivamente, para la puntuación de desacoplamiento. CONCLUSIONES: La puntuación de desacoplamiento de la captación de 18F-FDG/13N amonio se puede utilizar para discriminar entre GBG y BIL. El uso de un mapa de desacoplamiento de estos dos trazadores puede mejorar el análisis visual y la precisión del diagnóstico

PURPOSE: Accurate identification of low-grade gliomas (LGGs; World Health Organization grades I and II) and their differentiation from brain inflammation lesions (BILs) remains difficult; however, it is essential for treatment. This study assessed whether a one-day protocol for voxel-wise 18F-FDG and 13N-ammonia PET/CT with uptake decoupling analysis could differentiate LGGs from BILs. MATERIALS AND METHODS: Twenty-eight patients with LGGs and 16 patients with BILs underwent 18F-FDG and 13N-ammonia PET/CT on the same day before any type of therapy. The decoupling score and tumor-to-normal tissue (T/N) ratio of 18F-FDG and 13N-ammonia were calculated at each location. Student's t-test was used to compare values, and ROC curve analysis was used to establish a cut-off value for the T/N ratio and decoupling score. Area under the curve (AUC) was calculated to evaluate differential efficacy. RESULTS: Significant differences were observed in 13N-ammonia T/N ratio (p = 0.018) and decoupling score (p = 0.003) between LGGs and BILs; however, the 18F-FDG T/N ratio did not show any differences (p = 0.413). Optimal cut-off values for 18F-FDG T/N ratio, 13N-ammonia T/N ratio, and decoupling score were 0.73, 0.97, and 2.31, respectively, with corresponding AUCs of 0.48, 0.68, and 0.77. The respective sensitivity, specificity, and accuracy parameters using these cut-off values were 53.6%, 62.5%, and 56.8%, respectively, for 18F-FDG; 50.0%, 75.0%, and 59.1%, respectively, for 13N-ammonia; and 60.7%, 93.8%, and 72.7%, respectively, for decoupling score. CONCLUSIONS: 18F-FDG/13N-ammonia uptake decoupling score can be used to discriminate between LGGs and BILs. Use of a decoupling map of these two tracers can improve visual analysis and diagnostic accuracy

Modelo de evaluación de metabolismo y perfusión en el miocardio de rata mediante 18F-FDG, 1-11C-acetato, 13N-amoniaco y micro-tomografía por emisión de positrones (micro PET) / Cardiac metabolism and perfusion evaluation in a rat model using 18F-FDG,1- 11C-acetate, 13NH3 and micro-positron emission tomography (microPET)

Objetivos: Estandarizar un protocolo de adquisición para el estudio del metabolismo glucolítico, oxidativo y de perfusión miocárdicos en un modelo de rata. Métodos: Se realizaron estudios con los tres principales radiotrazadores usados para evaluar la función cardiaca: 18F-FDG para evaluar el metabolismo glucolítico en tres protocolos distintos; 1-11C-acetato para el metabolismo oxidativo y 13NH3 para la perfusión cardiaca. (18F-FDG)- cinco ratas Wistar macho en tres diferentes protocolos: con acceso a libre demanda de comida y agua; con ayuno de ocho horas y con ayuno de ocho horas más carga oral de glucosa al 50%. Se adquirieron imágenes del área torácica durante 30 minutos mediante microPET; 30 y 60 minutos post-administración de 370 - 555 MBq de 18F-FDG vía IP. (1-11C-acetato)- Se estudiaron ocho ratas. Cuatro estudios estáticos de 30 minutos y cuatro adquisiciones dinámicas de 30 minutos tras administración de 370 - 555 MBq de1-11C-acetato por vena caudal.(13NH3)- 10 estudios estáticos de 15 minutos después de una dosis IV de 370 - 555 MBq de 13NH3, bajo anestesia inhalada con isofluorano a 1.5% a 2%. Se realizó análisis comparativo y cualitativo de todas las imágenes obtenidas por dos médicos especialistas en el área y un análisis semi-cuantitativo mediante reconstrucciones 3D y selección de ROIs con el programa AMIDE en el caso de 18F-FDG. Resultados: Se determinó que las mejores imágenes para fines de evaluación metabólica del miocardio fueron las correspondientes a los 60 minutos post-administración de la 18F-FDG del protocolo sin ayuno. Se visualizó sin problemas el miocardio de rata de las imágenes estáticas con 1-11C-acetato, y mediante adquisición dinámica, se pudo apreciar la perfusión miocárdica. Las imágenes con 13NH3 permitieron observar una distribución homogénea del radiotrazador en los diferentes segmentos del ventrículo izquierdo en el eje corto, eje largo vertical y eje largo horizontal. Conclusiones: Se logró la estandarización de protocolos de adquisición de imágenes de los tres principales radiotrazadores utilizados para el estudio del metabolismo y perfusión cardiacos, en un modelo animal. Es factible establecer un protocolo válido para la valoración de perfusión, metabolismo glucolítico y oxidativo miocárdicos, con el fin de utilizarlo como punto de referencia para la evaluación de terapias génica, farmacológica o quirúrgica a nivel experimental.

Objective: To standardize an acquisition protocol for the study of myocardial glucolitic and oxidative metabolism and perfusion in a rat model. Methods: Studies were carried out with the three main radiopharmaceuticals used to assess heart function:[18F]-FDG for glucolitic metabolism; [1-11C]-acetate for oxidative metabolism and [13N]-NH3for myocardial perfusion.[18F]-FDG -Five Wistar adult male rats were studied in three different protocols: non-fasting group, fasting group,8 h before the study with water provided ad libitum, and a fasting group by the same time receiving an oral 50%-glucose solution. Thirty-minute scans were performed with a microPET Focus 120, 30 and 60 min after the administration of 370-555 MBq 18F-FDG. [1-11C]-Acetate -Eight rats were studied. Four static and four dynamic 30 min acquisitions after a 370-555 MBq of [1-11C]-acetate caudal vein administration.[13N]-NH3-Ten static studies were acquired 15 min post-administration of 370555 MBqof13NH3, under 1.5-2% isofluorane anesthesia. Comparative and visual analyses were performed by two experts in the field. A semi-quantitative analysis was performed using 3D reconstructions and ROI selections with AMIDE software. Results: The best images were those obtained from the non-fasting group, especially those taken at 60 min after the [18F]-FDG administration. High quality myocardial, static images were obtained with [1-11C]-acetate, and the dynamic acquisitions allowed the identification of myocardial perfusion. The 13NH3images showed a homogeneous distribution of the radiotracer in different segments of the short, long and horizontal axes in the left ventricle. Conclusions: It is possible to standardize the microPET acquisition protocols for the three main radiopharmaceuticals to evaluate the heart function in a rat model. It is feasible to establish a valid protocol for measuring glucolitic and oxidative myocardial metabolism and perfusion for gene, drug or surgical therapy assessment.

Breeding of high lipid producing strain of Geotrichum robustum by ion beam implantation

To obtain an industrial strain with high lipid yield, the wild strain G0 of Geotrichum robustum was mutated by means of nitrogen ions implantation. Mutagenic effects of strain G0 by low energy N+ ion implantation were studied. The experimental results indicated that the survival rate curve took a "saddle" shape, and the positive mutation rate was increased to 22.00 percent at the dose of nitrogen ions 2.0 x 10(15) ions/cm² when the survival rate was 28.60 percent. By repeated screening, a high lipid producing strain G9 was obtained. The biomass, lipid content and lipid yield of the mutant can reach 40.25 g/L, 71.14 percent and 28.63 g/L after cultured in a 5L fermenter for 8 days, increasing by 52.81 percent, 68.82 percent and 157.93 percent to those of wild strain, respectively. Analysis results on fatty acids composition and relative content by gas chromatography and mass spectrometry showed that the lipid in strain G9 was mainly composed of 16-carbon and 18-carbon fatty acids, including 37.360 percent oleic acid, 23.631 percent palmitic acid, 4.458 percent linoleic acid and 26.465 percent stearic acid. Such compositional features were quite similar to plant oil. Geotrichum robustum strain G9 may be an ideal high lipid producing strain for biodiesel production.

Enhancement of wanlongmycin production by nitrogen ion beam implantation / Mejora de la producción de wanlongmycin por implantación de haces iónicos de nitrógeno

In an attempt to obtain an industrial strain with higher yield of wanlongmycin, the wild strain Streptomyces griseovariabilis GAAS2507 was mutated by a novel mutagen, nitrogen ion beam with energy of 20 kilo electron volts (KeV) and dose ranging from 7.80 x 10(14) to 2.86 x 10(15) ions/cm². One mutant strain WN939 was obtained. Its yield of wanlongmycin reached 271.24 µg/mL, which was 82.10 percent higher than that of the wild strain. The mutant strain WN939 was relatively stable for the production of wanlongmycin through six successive transfers of cultures and a repeat fermentation in a 30 L fermentor. In addition, the mutant strains were investigated and divided into five types by their colony phenotypes and production of wanlongmycin. Among them, three types mutant strains exhibited positive mutation, while the other two types mutant strains exhibited negative mutation.

Nitrogen metabolism in the rat

The intermediary metabolism of 6 isotopic amino acids, 15N-aspartic acid, 15N-glutamic acid, 15N-alanine, 15N-glutamine (amide-15N), 15N-glycine and 15N-lysine (O-15N), and 15N-ammonium chloride were investigated. The aim of this study was to establish the precursor-product relationships existing between these amino acids, ammonia and urea in the amino-N pools of the major organs and tissue beds of the normal postprandial rat with the specific objective of following the movement of nitrogen to urea synthesis. It was hoped to ascertain whether glutamic acid played a central role in providing nitrogen for urea synthesis and whether there existed any relationship between 15N distribution patterns of the different isotopes and WBTP rates calculated from hepatic and renal urea-N enrichments. The method employed involved the administration of tracer quantities of the isotopes by the constant infusion technique and measuring the 15N excess of ammonia-N, glutamine amide-N, alanine-N, glutamate-N, aspartate-N and urea-N. It was found that nitrogen from 15N-alanine, 15N-aspartic acid and 15N-glutamic acid was distributed evenly in most of the amino-N pools studied. Nitrogen from the other four isotopes was distributed unevenly, preferentially to ammonia, glutamine amide and urea. 15N-glycine and 15N-lysine were only sparingly metabolised. WBPT rates obtained from urea-N enrichments were not affected by the nitrogen distribution patterns of the isotopes but by the extent to which they metabolised. WBPT rates calculated from ammonia-N enrichments were unduly affected by the extent to which each isotope contributed nitrogen to ammoniagenesis. Glutamic acid does not seem to be the precursor of both nitrogens used for urea synthesis. It supplies only one nitrogen. It is possible that urea is synthesised from an amino-N received via the glutamate to aspartate pathway and an amide-N received via the glutamine to ammonia to carbamyl phosphate pathway. Free ammonia entering the liver is first fixed as glutamine amide before being used for urea synthesis. (AU)

Comparison of 15N-labelled glycine, aspartate, valine and leucine for measurement of whole-body protein turnover

Whole-body protein turnover was measured in rats by constant infusion of 15N-labelled glycine, aspartate, valine and leucine and measuring the enrichment of hepatic and renal urea and ammonia nitrogen. The values obtained with [15N] glycine were comparable with values reported with methods based on different assumptions. [15N] Aspartate gave rise to an increased enrichment of urea and ammonia and hence to lower protein-turnover rates. [15N] Valine and [15N] leucine gave low enrichments of nitrogenous end products and hence to high protein-turnover rates. All 15N-labelled amino acids are not equally suitable for measuring whole-body protein turnover by the end-product method. The relative amounts of 15N going to the end products can be prodicted from the known individual metabolism of aspartate and the branched-chain amino acids (AU)

Protein turnover in man measured with 15N: comparison of end products and dose regimes

Whole-body protein synthesis was measured with [15N]glycine in malnourished and recovered infants and in obese patients. Comparisons were made: 1) between results obtained with single (S) and repeated (R) oral dosage of tracer; and 2) between urea and ammonia as end products. In the infants S and R gave similar values for the synthesis rate. With NH3 as end product were about two-thirds of those with urea. It is suggested that the cause of this result is that glycine contributes preferentially to the formation of urinary NH3 with NH3 as end product, a collection period of 12 h has been found to be suitable. With urea it is not possible to define an appropriate collection period. The combination of single dose of [15N] glycine with urinary NH3 as end product provides a simple method for measuring whole-body protein synthesis under clinical and field conditions. It can be repeated at short intervals and can give useful comparative information provided that conditions are carefully standardized. The reproducibility so far is ñ 13 percent. (AU)