Influencing factors of 13C-urea breath test in the diagnosis of Helicobacter pylori infection in children / 中华实用儿科临床杂志

The 13C-urea breath test is the most widely applied non-invasive test to diagnose Helicobacter pylori (Hp) infection in children.The fasting time, dose and formulation of labeled urea, type of test meal, time of breath collection, device to detect breath samples, cut-off value of exhaled 13CO 2/ 12CO 2 breath delta value and the interpretation of results have been modified to improve the accuracy.The 13C-urea breath test possesses a good perfor-mance in diagnosing Hp infection and evaluating the eradication of infection after treatment in children.However, the high false-positive results in young children are caused by oral flora, endogenous CO 2 and fixed dose of labeled urea.In addition, taking proton pump inhibitors, antibiotics and bismuth before test, low bacterial density and peptic ulcer bleeding will lead to false negative results.This study aims to review the influencing factors of 13C-urea breath test in the diagnosis of Hp infection in children.

Thirty years development of ¹³C metabolic flux analysis: a review / 生物工程学报

¹³C metabolic flux analysis (¹³C-MFA) enables the precise quantification of intracellular metabolic reaction rates by analyzing the distribution of mass isotopomers of proteinogenic amino acids or intracellular metabolites through ¹³C labeling experiments. ¹³C-MFA has received much attention as it can help systematically understand cellular metabolic characteristics, guide metabolic engineering design and gain mechanistic insights into pathophysiology. This article reviews the advances of ¹³C-MFA in the past 30 years and discusses its potential and future perspective, with a focus on its application in industrial biotechnology and biomedicine.

15N-NMR spectroscopic studies and investigation of spectral data property relationships of proton pump inhibitors

In this study, the relationships between 15N-NMR and 13C-NMR chemical shifts of omeprazole, lansoprazole, ilaprazole,pantoprazole, and rabeprazole and their physicochemical and pharmacokinetic properties, namely, pKa, half-life,tmax, logP, and protein binding were investigated. This study also presents the first report of 15N-NMR spectroscopicstudies of lansoprazole, pantoprazole, and ilaprazole. It was found that 15N-NMR chemical shifts of the doubly bondedbenzimidazole nitrogen of proton pump inhibitors showed correlation with pKa2, protein binding and logP, while 15NNMR chemical shifts of the pyridine nitrogen correlate with protein binding and tmax. Sum of 15N-NMR chemical shiftsand sum of 13C-NMR chemical shifts, both, exhibit correlation with half-life, logP, and tmax. The sum of 13C chemicalshifts of the pyridine moiety exhibits correlation with pKa1, while the sum of 13C chemical shifts of the benzimidazolemoiety exhibits correlation with half-life. NMR chemical shifts may, hence, be useful as molecular descriptors in thedevelopment of Quantitative Structure/Spectral Data Property Relationship models.

Visual FTBL Generator: Visual Generation Tool for 13C-FLUX File

Abstract 13C metabolic flux analysis (13C-MFA) has achieved increasing significance in quantitative metabolic system analysis in recent years. In 13C metabolic flux analysis, 13C-FLUX software is a major analytical tool. The software's input script is primarily expressed in textual form without visual presentation of the structure of the entire metabolic network, thus error-prone in manual input. To solve this problem, we have developed a visual FTBL generator (VFG, available at http://47.100.98.220/vfg/index.jsp in a Google or Firefox browser)for MFA that eliminates the tedious, error-prone text entry mode and provides a user-friendly graphical interface and simple visual reaction generation functions.

Triterpene saponins in Panax japonicus and their ~(13)C-NMR spectroscopic characteristics / 中国中药杂志

Panax japonicus( PJ) is a valuable medicinal plant belonging to the genus Panax of Araliaceae,the recumbent rhizome of which is widely used in clinic therapy,healthcare products and as cosmetic additives with functions of dissipating stasis,reducing swelling,stanching bleeding,and reinforcing deficiency,etc. PJ contains abundant levels of oleanane-and dammarane-type triterpene saponins,which are considered as the material basis for exerting pharmacodynamic action. Based on the previous researches,more than110 triterpene saponins have been reported from PJ. These triterpene saponins were summarized in this review,and could be classified into dammarenediol Ⅱ,protopanaxadiol,protopanaxatiol,ocotillol,oleanolic acid,ursolic acid and miscellaneous subtypes,according to their molecular skeletons in biosynthesis processes. Further more,the structural features of these triterpene saponins in the seven different subtypes,together with their~(13)C-NMR spectroscopic characteristics were described,hoping to provide available information for chemical diversity research of PJ.

13C NMR Analysis: Terpenoids, Steroids and Carotenoid from Diospyros soubreana (Ebenaceae)

Phytochemical investigations on bark of trunks and leaves of Diospyros soubreana (Ebenaceae) led to the isolation and characterisation of nine molecules: one monocyclic sesquiterpenoid lactone (1), five pentacyclic triterpenes (2, 3, 4, 5 and 6), two sterols (7 and 8) and one carotenoid alcohol (9), all isolated for the first time from this species. The structural elucidation of these compounds was carried out by 13C NMR spectroscopy.

Correlation between Helicobacter pylori infections and serum lipid abnormality in adult population of healthy physical examination / 重庆医学

Objective To explore the relationship between Helicobacter pylori (HP) infection and dyslipidemia in adult people undergoing the healthy physical examination in Kunming city.Methods The intact population data of adult people undergoing the healthy physical examination and conducting the HP detection by adopting the 13C breath test (13 C-UBT)in the Cadres Physical Examination Center,Yunnan Provincial Second People's Hospital from January 2013 to February 2015 were retrospectively analyzed.The data included the basic information and serum fipids indexes[total cholesterol (TC),triglyceride (TG),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C)].All subjects were divided into the HP positive group and HP negative group according to whether having HP infection.The levels of TC,TG,HDL-C,LDL-C and the incidences of single index of dyslipidemia and total dyslipidemias were compared between 2 groups and Logistic regression analysis was performed for investigating the relationship between HP infection and dyslipidemia.Results A total of 1 354 subjects were included in the study.The HP infection rate was 33.2％.The levels of TC,TG,HDL-C and LDL-C were no statistical significance between positive HP group and negative HP group (P＞0.05).The incidence rate of TC≥6.22 mmol/L of HP positive group was lower than that of HP negative group (P＜0.05).The occurrence rate of TC increase abnormality in the HP positive group was lower than that in the HP negative group (P＜0.05);the occurrence rate of dyslipidemia had no statistical difference between the HP positive group and HP negative group in the stratification according to sex,age and BMI (P＞0.05).The regression analysis showed that the HP infection was an independent influencing factors of TC increase abnormality (OR=0.644,P＜0.05).Conclusion The HP infection affects the incidence of TC increase abnormality,but might not affect the occurrence rate of dyslipidemia.

Determination of asenapine in presence of its inactive metabolites in human plasma by LC-MS/MS / 药物分析学报

A highly selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been described for the determination of asenapine (ASE) in presence of its inactive metabolites N-desmethyl asenapine (DMA) and asenapine-N-glucuronide (ASG). ASE, and ASE 13C-d3, used as in-ternal standard (IS), were extracted from 300 μL human plasma by a simple and precise liquid-liquid extraction procedure using methyl tert-butyl ether. Baseline separation of ASE from its inactive meta-bolites was achieved on Chromolith Performance RP8e(100 mm × 4.6 mm) column using acetonitrile-5.0 mM ammonium acetate-10% formic acid (90:10:0.1, v/v/v) within 4.5 min. Quantitation of ASE was done on a triple quadrupole mass spectrometer equipped with electrospray ionization in the positive mode. The protonated precursor to product ion transitions monitored for ASE and ASE 13C-d3 were m/z 286.1 → 166.0 and m/z 290.0 → 166.1, respectively. The limit of detection (LOD) and limit of quantitation (LOQ) of the method were 0.0025 ng/mL and 0.050 ng/mL respectively in a linear con-centration range of 0.050–20.0 ng/mL for ASE. The intra-batch and inter-batch precision (% CV) and mean relative recovery across quality control levels were ≤5.8% and 87.3%, respectively. Matrix effect, eval-uated as IS-normalized matrix factor, ranged from 1.03 to 1.05. The stability of ASE under different storage conditions was ascertained in presence of the metabolites. The developed method is much simpler, matrix free, rapid and economical compared to the existing methods. The method was suc-cessfully used for a bioequivalence study of asenapine in healthy Indian subjects for the first time.

Performance of the 13C-urea breath test for the diagnosis of H. pylori infection using a substrate synthesized in Brazil: A preliminary study

OBJECTIVE: The 13C-urea breath test is the main non-invasive test for the diagnosis of Helicobacter pylori infection. The availability of this test throughout the country is limited, mainly due to the difficulty in obtaining the labeled isotope from abroad. Recently, researchers from the Nuclear Energy Center in Agriculture at the University of São Paulo (CENA/USP) succeeded in synthesizing 13C-enriched urea for Helicobacter pylori diagnosis. The aim of the study was to compare the performance of the 13C-urea breath test using 13C-urea acquired abroad with that of a test using 13C-urea synthesized in Brazil. METHOD: Sixty-four dyspeptic patients participated in the study (24 men and 40 women). Initially, the patients performed the 13C-urea breath test using the imported substrate (Euriso-Top, France). Seven to fourteen days later, all the patients repeated the test using the Brazilian substrate. The samples from both examinations were processed in an infrared isotope analyzer (IRIS, Wagner Analisen Technik, Germany), and all delta over baseline (DOB) [%] values above four were considered positive results. RESULTS: Twenty-seven patients (42%) exhibited negative results for Helicobacter pylori infection, and thirty-seven patients (58%) exhibited positive results when tested using the foreign substrate (gold standard). There was a 100% concordance regarding the presence or absence of infection when the gold standard results were compared with those obtained using the Brazilian substrate. CONCLUSIONS: Similar performance in the diagnosis of Helicobacter pylori infection was demonstrated when using the 13C-urea breath test with the Brazilian 13C-urea substrate and the test with the substrate produced abroad. This validation represents an important step toward increasing the availability of the 13C-urea breath test throughout the country, which will have a positive influence on the management of Helicobacter pylori infection.

Chemical composition of the leaf oil of Artabotrys jollyanus from Côte d'Ivoire

ABSTRACT One oil sample isolated from leaves of Artabotrys jollyanus Pierre, Annonaceae, from Côte d'Ivoire has been analyzed by GC(RI), GC-MS and 13C NMR. In total, thirty-seven compounds accounting for 96.9% of the relative composition have been identified. The composition of the essential oil was dominated by trans-calamenene (15.7%), α-copaene (14.8%), α-cubebene (10.4%), cadina-3,5-diene (10.3%), (E)-β-caryophyllene (6.3%) and cadina-1,4-diene (6.1%). 13C NMR spectroscopy was very useful in the identification of trans-calamenene, 7-hydroxycalamenene, cadina-3,5-diene and cadina-1,4-diene. Moreover, monitoring the evolution of the leaf essential oil composition and the yield on a 12-month period (one sample per month) was achieved. The twelve essential oil samples exhibited a chemical homogeneity but the yield varied from sample to sample (0.26-0.60%).

Analysis of the current infection status and risk factors of Helicobacter pylori among people taken physical examination in Miyun area of Beijing / 中国综合临床

Objective To analyze the infection status and possible risk factors of Helicobacter pylori among people taken physical examination in Miyun area of Beijing,so as to establish effective intervention measures scientifically.Methods From January 2012 to December 2016,eleven thousand physical examinees in Beijing MIyun Hospital were enrolled in this study,13C-urea breath test was used to detect Helicobacter pylori infection and a face to face questionnaire survey was applied.The data colleted was analyzed based on sex,age, living habits.Results The overall infection rate of Hp was 46.72%(5139/11000),the rate of male infection was higher than that of female(49.74%(2826/5682)vs.43.49%(2313/5318)),and the difference was statistically significant(χ2=43.000,P<0.000).The physical examinees were divided into 4 groups by 20 years for age.The infection rates of Hp in the<20 years old group,20—39 years old group,40-59 years old group,>60 years old group were 36.17%,47.28%,48.04%,43.59%,respectively.The infection rate before the age of 60 was on the rise,and the infection rate was the highest in the 40-59 year group,the lowest in the<20 years old group.There was significant difference among the 4 groups(χ2=23.694,P=0.000).The Hp infection rate in people who smoked,had a large number of family members and preferred a hot diet,a dinner party and no hand washing habits was significantly higher than those without related habits,the differences were statistically significant(P<0.05).Conclusion The infection rate of Hp infection in the MIyun area is lower than that of the national average.The infection distribution is closely related with sex,age and living habits.Health education should be strengthened and the occurrence of food-borne disease should be prevented to reduce the Hp infection rate.

Analysis of the current infection status and risk factors of Helicobacter pylori among people taken physical examination in Miyun area of Beijing / 中国综合临床

Objective To analyze the infection status and possible risk factors of Helicobacter pylori among people taken physical examination in Miyun area of Beijing,so as to establish effective intervention measures scientifically.Methods From January 2012 to December 2016,eleven thousand physical examinees in Beijing MIyun Hospital were enrolled in this study,13C-urea breath test was used to detect Helicobacter pylori infection and a face to face questionnaire survey was applied.The data colleted was analyzed based on sex,age, living habits.Results The overall infection rate of Hp was 46.72%(5139/11000),the rate of male infection was higher than that of female(49.74%(2826/5682)vs.43.49%(2313/5318)),and the difference was statistically significant(χ2=43.000,P<0.000).The physical examinees were divided into 4 groups by 20 years for age.The infection rates of Hp in the<20 years old group,20—39 years old group,40-59 years old group,>60 years old group were 36.17%,47.28%,48.04%,43.59%,respectively.The infection rate before the age of 60 was on the rise,and the infection rate was the highest in the 40-59 year group,the lowest in the<20 years old group.There was significant difference among the 4 groups(χ2=23.694,P=0.000).The Hp infection rate in people who smoked,had a large number of family members and preferred a hot diet,a dinner party and no hand washing habits was significantly higher than those without related habits,the differences were statistically significant(P<0.05).Conclusion The infection rate of Hp infection in the MIyun area is lower than that of the national average.The infection distribution is closely related with sex,age and living habits.Health education should be strengthened and the occurrence of food-borne disease should be prevented to reduce the Hp infection rate.

Accurate Detemination of Isotopic Abundance of Intracellular Metabolites of Saccharopolysporaerythraea Based on Ultra Performance Liquid Chromatography-Triple Quadrupole Mass Spectrometry / 分析化学

A method for measuring 13C isotopic abundance of intracellular metabolites of Saccharopolysporaerythraea by ultra-high performance liquid chromatography (UPLC)-triple quadrupole mass spectrometry was established.First, the chromatographic conditions of UPLC were optimized, and then the MS conditions such as unique tube lens voltage, collision energy, and ion pair were optimized.On the bases of length of the parent and daughter ions carbon chains and whether the daughter ions contain 13C atoms, the one-to-one method, one-to-many method and SIM method were established for measuring 13C isotopic abundance.Then these methods were used to measure naturally labeled intracellular metabolite standards and 13C labeled samples, and according to the gap between the experimental value and the theoretical value, the best method was established for each metabolite of different characteristics.The results showed that one-to-one method was most effective for measuring the metabolites of daughter ions not containing 13C atoms represented by sugar phosphates, one-to-many method was the best for measuring the metabolites of both parent and daughter ions containing 13C short carbon chains represented by carboxylic acids, SIM method could play a role in measuring the metabolites of both parent and daughter ions containing 13C long carbon chains represented by coenzyme A.This method had a good measurement precision and could be applied to the measurement of Saccharopolysporaerythraea intracellular metabolites, which contributed to the consequent study of metabolic mechanism and the efficient expression of erythromycin.

Rate of active Helicobacter pylori infection among symptomatic patients of Pakistan

Only few epidemiological studies have examined the rate of active H. pylori infection in the symptomatic population in Pakistan. This retrospective study presents the laboratory data collected during the past 13 years (2002 to 2015) from 2315 symptomatic patients referred to the BreathMAT Lab, Nuclear Medicine, Oncology and Radiotherapy Institute, Islamabad for the diagnosis of active H. pylori infection using the 13C Urea Breath Test. Rate of infection and its association with gender and age were evaluated. The overall rate of active H. pylori infection was 49.5% and there was no association of this rate of infection with gender. An increase in rate of infection was observed with increasing age with significant difference (p < 0.05). The patients that tested negative for this infection might be having symptoms due to stress and indiscriminate use of non-steroidal antiinflammatory drugs (NSAIDs) in this community. The fact that half of the symptomatic patients were negative needs to be highlighted and further suggests that symptomatic patients should be tested by the 13C UBT before prescribing antibiotic treatment for H. pylori eradication. In addition, there is a need to educate this community about the harmful and side effects of self medication and overuse of NSAIDs.

Content Determination of Urea in Urea [13C] Capsules by High Performance Cation-exchange Chromatogra-phy / 中国药房

OBJECTIVE:To determine the content of urea in Urea [13C] capsules by high performance cation-exchange chroma-tography (HPCEC). METHODS:The determination was performed on Zorbax 300 SCX column with mobile phases consisting of acetonitrile-0.1% phosphoric acid (20:80,V/V) at the flow rate of 1.0 mL/min. The detection wavelength was set at 200 nm and column temperature was 35 ℃. The sample size was 20 μL. RESULTS:The linear range of urea was 0.0039-1.0030 mg/ml(r=0.9997). The limit of quantitation was 3.918 μg/mL and the limit of detection was 0.975 μg/mL. RSDs of precision,stability and repetitive test were all lower than 2.0%. The recovery ranged 99.3%-101.0%(RSD=0.67%,n=9). CONCLUSIONS:The meth-od is simple,rapid,sensitive and suitable for the content determination of urea in Urea [13C] capsules.

Dual Component Analysis for In Vivo T₂* Decay of Hyperpolarized ¹³C Metabolites

PURPOSE: To investigate the exchange and redistribution of hyperpolarized ¹³C metabolites between different pools by temporally analyzing the relative fraction of dual T₂* components of hyperpolarized ¹³C metabolites. MATERIALS AND METHODS: A dual exponential decay analysis of T₂* is performed for [1-¹³C] pyruvate and [1-¹³C] lactate using nonspatially resolved dynamic ¹³C MR spectroscopy from mice brains with tumors (n = 3) and without (n = 4) tumors. The values of shorter and longer T₂* components are explored when fitted from averaged spectrum and temporal variations of their fractions. RESULTS: The T₂* values were not significantly different between the tumor and control groups, but the fraction of longer T₂* [1-¹³C] lactate components was more than 10% in the tumor group over that of the controls (P < 0.1). The fraction of shorter T₂* components of [1-¹³C] pyruvate showed an increasing tendency while that of the [1-¹³C] lactate was decreasing over time. The slopes of the changing fraction were steeper for the tumor group than the controls, especially for lactate (P < 0.01). In both pyruvate and lactate, the fraction of the shorter T₂* component was always greater than the longer T₂* component over time. CONCLUSIONS: The exchange and redistribution of pyruvate and lactate between different pools was investigated by dual component analysis of the free induction decay signal from hyperpolarized ¹³C experiments. Tumor and control groups showed differences in their fractions rather than the values of longer and shorter T₂* components. Fraction changing dynamics may provide an aspect for extravasation and membrane transport of pyruvate and lactate, and will be useful to determine the appropriate time window for acquisition of hyperpolarized ¹³C images.

13C-methacetin breath test for evaluating of children's liver disorder / 中华实用儿科临床杂志

Objective To explore the clinical value of 13C-methacetin breath test for the assessment of liver disorder and to analyze its predictive value to the severity of liver function injury in children.Methods Eighteen healthy children served as healthy control group,and 40 patients with different etiology and severity served as experimental group,and then the latter were divided into 2 subgroups,28 patients in Child-Pugh classification A,and 12 cases in below B(11 cases in B and 1 case in C).An oral dose of 2 mg/kg tracer 13C-methacetin was administered to each subject for the 13 C-methacetin breath test.At the same time,serum liver function markers including serum transaminase,bilirubin,albumin and prothrombin time were measured.The acquired data were analyzed by SPSS 17.0 software.Results (1) Metabolisation velocity (MV) max30 and cumulated dose (CUM) 120 in experimental group (46.64 ± 27.93,59.29 ± 30.73) were much lower than those of the healthy control group(73.56 ± 26.03,102.97 ± 41.80) (t =2.450,3.165,all P ＜0.05);(2) MVmax30 and CUM120 were closely correlated with the liver function markers of albumin,total bilirubin,direct bilirubin,prothrombin time (P ＜ 0.05);(3) MVmax30 and CUM120 could predict liver diseases in children,especially the CUM120.With CUM120 =85.80 as a cut-off value to predict liver diseases,the Youden index was 0.578 at its maximum,and the sensitivity and specificity were 77.8％ and 80.0％;(4) Compared with the Child-Pugh classification A,the CUM120 in Child-Pugh classification B and lower B was significantly lower(P ＜ 0.001);(5) CUM120 could predict the severity of liver diseases.With CUM120 =56.15 as a cut off value to predict the severity of liver diseases,the Youden index was 0.857 at its maximum,and the sensitivity and specificity were 85.7％ and 100.0％.Conclusion 13C-methacetin breath test index of CUM120 could predict liver diseases in children and the severity of liver function.

Alternating Acquisition Technique for Quantification of in vitro Hyperpolarized 1-13C Pyruvate Metabolism

PURPOSE: To develop a technique for quantifying the 13C-metabolites by performing frequency-selective hyperpolarized 13C magnetic resonance spectroscopy (MRS) in vitro which combines simple spectrally-selective excitation with spectrally interleaved acquisition. METHODS: Numerical simulations were performed with varying noise level and K(p) values to compare the quantification accuracies of the proposed and the conventional methods. For in vitro experiments, a spectrally-selective excitation scheme was enabled by narrow-band radiofrequency (RF) excitation pulse implemented into a free-induction decay chemical shift imaging (FIDCSI) sequence. Experiments with LDH / NADH enzyme mixture were performed to validate the effectiveness of the proposed acquisition method. Also, a modified two-site exchange model was formulated for metabolism kinetics quantification with the proposed method. RESULTS: From the simulation results, significant increase of the lactate peak signal to noise ratio (PSNR) was observed. Also, the quantified K(p) value from the dynamic curves were more accurate in the case of the proposed acquisition method compared to the conventional non-selective excitation scheme. In vitro experiment results were in good agreement with the simulation results, also displaying increased PSNR for lactate. Fitting results using the modified two-site exchange model also showed expected results in agreement with the simulations. CONCLUSION: A method for accurate quantification of hyperpolarized pyruvate and the downstream product focused on in vitro experiment was described. By using a narrow-band RF excitation pulse with alternating acquisition, different resonances were selectively excited with a different flip angle for increased PSNR while the hyperpolarized magnetization of the substrate can be minimally perturbed with a low flip angle. Baseline signals from neighboring resonances can be effectively suppressed to accurately quantify the metabolism kinetics.

Multi-components compatibility theory of Chinese materia medica and IGD 13C-NMR coupling fingerprint / 中草药

Multi-components compatibility theory of Chinese materia medica (CMM) has been more and more mature and perfect, because of the efforts of many scientific and technological workers for nearly 20 years. Omics, compatibility, and fingerprint are the three key words of the multi-components compatibility theory. Namely in multi-components compatibility theory, modern "omics" and traditional "compatibility" are closely combined through "fingerprint". The modernization of CMM has developed to such a stage that the fingerprint (especially IGD 13C-NMR coupling fingerprint) method could be used to study morden CMM under the guidance of multi-components compatibility theory.

Determination of Optimal Scan Time for the Measurement of Downstream Metabolites in Hyperpolarized 13C MRSI

PURPOSE: For a single time-point hyperpolarized 13C magnetic resonance spectroscopy imaging (MRSI) of animal models, scan-time window after injecting substrates is critical in terms of signal-to-noise ratio (SNR) of downstream metabolites. Prescans of time-resolved magnetic resonance spectroscopy (MRS) can be performed to determine the scan-time window. In this study, based on two-site exchange model, protocol-specific simulation approaches were developed for 13C MRSI and the optimal scan-time window was determined to maximize the SNR of downstream metabolites. MATERIALS AND METHODS: The arterial input function and conversion rate constant from injected substrates (pyruvate) to downstream metabolite (lactate) were precalibrated, based on pre-scans of time-resolved MRS. MRSI was simulated using twosite exchange model with considerations of scan parameters of MRSI. Optimal scantime window for mapping lactate was chosen from simulated lactate intensity maps. The performance was validated by multiple in vivo experiments of BALB/C nude mice with MDA-MB-231 breast tumor cells. As a comparison, MRSI were performed with other scan-time windows simply chosen from the lactate signal intensities of prescan time-resolved MRS. RESULTS: The optimal scan timing for our animal models was determined by simulation, and was found to be 15 s after injection of the pyruvate. Compared to the simple approach, we observed that the lactate peak signal to noise ratio (PSNR) was increased by 230%. CONCLUSIONS: Optimal scan timing to measure downstream metabolites using hyperpolarized 13C MRSI can be determined by the proposed protocol-specific simulation approaches.