Pathways of N2O production by marine ammonia-oxidizing archaea determined from dual-isotope labeling.

The ocean is a net source of the greenhouse gas and ozone-depleting substance, nitrous oxide (N2O), to the atmosphere. Most of that N2O is produced as a trace side product during ammonia oxidation, primarily by ammonia-oxidizing archaea (AOA), which numerically dominate the ammonia-oxidizing community in most marine environments. The pathways to N2O production and their kinetics, however, are not completely understood. Here, we use 15N and 18O isotopes to determine the kinetics of N2O production and trace the source of nitrogen (N) and oxygen (O) atoms in N2O produced by a model marine AOA species, Nitrosopumilus maritimus. We find that during ammonia oxidation, the apparent half saturation constants of nitrite and N2O production are comparable, suggesting that both processes are enzymatically controlled and tightly coupled at low ammonia concentrations. The constituent atoms in N2O are derived from ammonia, nitrite, O2, and H2O via multiple pathways. Ammonia is the primary source of N atoms in N2O, but its contribution varies with ammonia to nitrite ratio. The ratio of 45N2O to 46N2O (i.e., single or double labeled N) varies with substrate ratio, leading to widely varying isotopic signatures in the N2O pool. O2 is the primary source for O atoms. In addition to the previously demonstrated hybrid formation pathway, we found a substantial contribution by hydroxylamine oxidation, while nitrite reduction is an insignificant source of N2O. Our study highlights the power of dual 15N-18O isotope labeling to disentangle N2O production pathways in microbes, with implications for interpretation of pathways and regulation of marine N2O sources.

Effects of increasing atmospheric CO2 on leaf water δ18O values are small and are attenuated in grasses and amplified in dicotyledonous herbs and legumes when transferred to cellulose δ18O values.

The oxygen isotope composition of cellulose (δ18O values) has been suggested to contain information on stomatal conductance (gs) responses to rising pCO2. The extent by which pCO2 affects leaf water and cellulose δ18O values (δ18OLW and δ18OC) and the isotope processes that determine pCO2 effects on δ18OLW and δ18OC are, however, unknown. We tested the effects of pCO2 on gs, δ18OLW and δ18OC in a glasshouse experiment, where six plant species were grown under pCO2 ranging from 200 to 500 ppm. Increasing pCO2 caused a decline in gs and an increase in δ18OLW, as expected. Importantly, the effects of pCO2 on gs and δ18OLW were small and pCO2 effects on δ18OLW were not directly transferred to δ18OC but were attenuated in grasses and amplified in dicotyledonous herbs and legumes. This is likely because of functional group-specific pCO2 effects on the model parameter pxpex. Our study highlights important uncertainties when using δ18OC as a proxy for gs. Specifically, pCO2-triggered gs effects on δ18OLW and δ18OC are possibly too small to be detected in natural settings and a pCO2 effect on pxpex may render the commonly assumed negative linkage between δ18OC and gs to be incorrect, potentially confounding δ18OC based gs reconstructions.

Values for the Digestibility of Pea Protein Isolate or Casein Amino Acids Determined using the Dual Isotope Method Are Not Similar to Those Derived with the Standard Ileal Balance Method in Healthy Volunteers.

BACKGROUND: The measurement of ileal amino acid (AA) digestibility is invasive and inappropriate when applied to vulnerable populations. The dual isotope method has been developed over the past 5 y as an alternative method. OBJECTIVE: The aim of this work was to compare the indispensable amino acid (IAA) digestibility values of 2 different proteins obtained using the dual isotope and the standard ileal balance methods in the same subjects. METHODS: Fifteen healthy adults completed the study. Over 4 h, they ingested 9 successive portions of mashed potatoes containing the test protein (pea protein or casein) labeled intrinsically with 15N and 2H, and a 13C-free AA mixture as a reference for the dual isotope method. Plasma was sampled regularly over the 8-h postprandial period, whereas the ileal digesta was collected continuously via a naso-ileal tube. Isotopic enrichments (15N and 13C) were measured in the digesta for the direct determination of ileal IAA digestibility, whereas plasma enrichments (2H and 13C) were measured to determine IAA digestibility using the dual isotope method. RESULTS: The 4-h repeated meal procedure enabled the almost complete digestion of test proteins at 8 h and the attainment of a plasma isotopic plateau between 2.5 and 4 h. These conditions were necessary to perform the ileal balance and dual isotope methods simultaneously. For pea protein, the mean IAA digestibility was similar between the 2 methods, but significant differences (from 10% to 20%) were observed for individual IAA values. For casein, IAA digestibility was significantly lower with the dual isotope method for all the IAA analyzed. CONCLUSIONS: Under our experimental conditions, the degree of agreement between the dual isotope and ileal balance methods varied among AAs and depended on the protein source. Further research is needed to validate the dual isotope method. This study was registered at clinicaltrials.gov as NCT04072770.

Measurement of True Indispensable Amino Acid Digestibility by the Dual Isotope Tracer Technique: A Methodological Review.

The digestible indispensable amino acid score uses ileal digestibility of each indispensable amino acid (IAA) of a dietary protein to calculate its protein quality. However, true ileal digestibility, which is the exclusive sum of digestion and absorption of a dietary protein up to the terminal ileum, is difficult to measure in humans. It is traditionally measured using invasive oro-ileal balance methods but can be confounded by endogenous secreted protein in the intestinal lumen, although the use of intrinsically labeled protein corrects for this. A recent, minimally invasive dual isotope tracer technique is now available to measure true IAA digestibility of dietary protein sources. This method involves simultaneous ingestion of 2 intrinsically but differently (stable) isotopically labeled proteins, a (2H or 15N-labeled) test protein and (13C-labeled) reference protein whose true IAA digestibility is known. Using a plateau-feeding protocol, the true IAA digestibility is determined by comparing the steady state ratio of blood to meal test protein IAA enrichment to the similar reference protein IAA ratio. The use of intrinsically labeled protein also distinguishes between IAA of endogenous and dietary origin. The collection of blood samples makes this method minimally invasive. As the α-15N and α-2H atoms of AAs of the intrinsically labeled protein are prone to label loss because of transamination, underestimation of digestibility, appropriate correction factors need to be employed when using 15N or 2H labeled test protein. The true IAA digestibility values of highly digestible animal protein by the dual isotope tracer technique are comparable to that measured by direct oro-ileal balance measurements, but no data are yet available for proteins with lower digestibility. A major advantage is that the minimally invasive method allows for true IAA digestibility measurement in humans across different age groups and physiological conditions.

Use of Isotope-Labeled Body or Dietary Proteins to Determine Dietary Amino Acid Digestibility.

Amino acid (AA) digestibility in humans has been determined conventionally based on oro-ileal AA disappearance. With this approach, it is necessary to account for undigested AAs of body origin (endogenous AAs) found in the ileal digesta. Determination of the endogenous AAs under physiological conditions is not straightforward, and the use of isotopes (labeled foods or body tissues) has been pivotal to advancing our understanding. The application of isotopes for determining gut endogenous AAs and AA digestibility is discussed as well as the types of digestibility coefficient generated (apparent, true, real) dependent upon methodology. Recently a new dual isotope-based method for determining ileal AA digestibility in humans has been developed that obviates the collection of ileal digesta. The dual isotope method, which awaits full validation, offers considerable promise for making noninvasive measures of AA digestibility in humans of different ages and physiological states.

Contribution of Ammonium-Induced Nitrifier Denitrification to N2O in Paddy Fields.

Paddy fields are one of the most important sources of nitrous oxide (N2O), but biogeochemical N2O production mechanisms in the soil profile remain unclear. Our study used incubation, dual-isotope (15N-18O) labeling methods, and molecular techniques to elucidate N2O production characteristics and mechanisms in the soil profile (0-60 cm) during summer fallow, rice cropping, and winter fallow periods. The results pointed out that biotic processes dominated N2O production (72.2-100%) and N2O from the tillage layer accounted for 91.0-98.5% of total N2O in the soil profile. Heterotrophic denitrification (HD) was the main process generating N2O, contributing between 53.4 and 96.6%, the remainder being due to ammonia oxidation pathways, which was further confirmed by metagenomics and quantitative polymerase chain reaction (qPCR) assays. Nitrifier denitrification (ND) was an important N2O production source, contributing 0-46.6% of total N2O production, which showed similar trends with N2O emissions. Among physicochemical and biological factors, ammonium content and the ratio of total organic matter to nitrate were the main driving factors affecting the contribution ratios of the ammonia oxidation pathways and HD pathway, respectively. Moisture content and pH affect norC-carrying Spirochetes and thus the N2O production rate. These findings confirm the importance of ND to N2O production and help to elucidate the impact of anthropogenic activities, including tillage, fertilization, and irrigation, on N2O production.

The True Amino Acid Digestibility of 15N-Labelled Sunflower Biscuits Determined with Ileal Balance and Dual Isotope Methods in Healthy Humans.

BACKGROUND: Sunflower is a promising protein source but data on amino acid (AA) digestibility are lacking in humans. Classically, the determination of AA digestibility requires ileal digesta sampling. The dual isotope method is minimally invasive but has not been compared to the conventional approach. OBJECTIVES: This study aimed to determine the true ileal digestibility of sunflower AAs in healthy volunteers who ate biscuits containing 15nitrogen (N) protein isolate, in comparison with the dual isotope method. METHODS: Twelve healthy volunteers (men and women; 40.4 ± 10.5 years old; BMI, 23.7 ± 2.9 kg/m2) were equipped with a naso-ileal tube. For 4 hours, they consumed 9 repeated meals comprising 15N-sunflower protein biscuits together with 13carbon (C)-AAs, carried either in chocolate (SUN + Ch; n = 7) or apple puree (SUN + P; n = 5). Ileal digesta and blood were sampled throughout 8 hours after ingestion of the first meal. The 15N and 13C AA enrichments were measured in digesta to determine ileal digestibility directly and in plasma to determine lysine and threonine digestibility using the dual isotope method. Differences between methods and between vector groups were analyzed using paired and unpaired t-tests, respectively. RESULTS: The ileal digestibility of sunflower indispensable AAs (IAA) was 89% ± 5.3%, with threonine and lysine having the lowest digestibility. In the SUN + Ch meal, IAA digestibility was 3% below that of SUN + P (P < 0.05). The mean free 13C-AA ileal digestibility was 98.1% ± 0.9%. No matter which matrix was used to carry 13C-AAs, plasma 15N and 13C-AA kinetics displayed a 1-hour offset. Digestibility obtained with the dual isotope method (70.4% ± 6.0% for threonine and 75.9% ± 22.3% for lysine) was below the target values. CONCLUSIONS: The ileal digestibility of IAAs from a sunflower isolate incorporated in a biscuit was close to 90% in healthy adults. Under our experimental conditions, the dual isotope method provided lower values than the usual method. Further protocol developments are needed to validate the equivalence between both methods. This trial was registered at clinicaltrials.gov as NCT04024605.

Using the dual isotope method to assess cecal amino acid absorption of goat whey protein in rats, a pilot study.

Measurement of ileal amino acids (AA) bioavailability is recommended to evaluate protein quality. A dual isotope tracer method, based on plasma isotopic enrichment ratios, has been proposed to determine true digestibility in humans. In a pilot study, we aimed to evaluate whether this method could be implemented in rats to determine AA bioavailability based on isotopic enrichment ratios measured in cecal digesta or plasma samples. Goat milk proteins were intrinsically labeled with 15N and 2H. Wistar rats were fed a meal containing the doubly labeled goat whey proteins and a tracer dose of 13C-spirulina. Blood samples were collected 0, 1 h and 3 h after meal ingestion from the tail vein. The rats were euthanized 4 h (n = 6) or 6 h (n = 6) after meal to collect plasma and intestinal contents. True orocecal protein digestibility and AA bioavailability were assessed by means of 15N and 2H enrichment in cecum content and compared with absorption indexes determined at the plasma or cecum level using isotopic ratios. Plasma kinetics of isotopic enrichment could not be completed due to the limited quantity of plasma obtained with sequential blood collection. However, the absorption indexes determined from cecal 15N or 2H/13C ratios gave coherent values with true orocecal AA bioavailability. This dual isotope approach with measurements of isotopic ratios in digestive content could be an interesting strategy to determine true AA bioavailability in ileal digesta of rats.

Source Diversity of Intermediate Volatility n-Alkanes Revealed by Compound-Specific δ13C-δD Isotopes.

Intermediate volatility organic compounds (IVOCs) are important precursors of secondary organic aerosols, and their sources remain poorly defined. N-alkanes represent a considerable portion of IVOCs in atmosphere, which can be well identified and quantified out of the complex IVOC pool. To investigate the potential source diversity of intermediate volatility n-alkanes (IVnAs, nC12-nC20), we apportioned the sources of IVnAs in the atmosphere of four North China cities, based on their compound-specific δ13C-δD isotope compositions and Bayesian model analysis. The concentration level of IVnAs reached 1195 ± 594 ng/m3. The δ13C values of IVnAs ranged -32.3 to -27.6‰ and δD values -161 to -90‰. The δD values showed a general increasing trend toward higher carbon number alkanes, albeit a zigzag odd-even prevalence. Bayesian MixSIAR model using δ13C and δD compositions revealed that the source patterns of individual IVnAs were inconsistent; the relative contributions of liquid fossil combustion were higher for lighter IVnAs (e.g., nC12-nC13), while those of coal combustion were higher for heavier IVnAs (e.g., nC17-nC20). This result agrees with principal component analysis of the dual isotope data. Overall, coal combustion, liquid fossil fuel combustion, and biomass burning contributed about 47.8 ± 0.1, 35.7 ± 4.0, and 16.3 ± 4.2% to the total IVnAs, respectively, highlighting the importance of coal combustion as an IVnA source in North China. Our study demonstrates that the dual-isotope approach is a powerful tool for source apportionment of atmospheric IVOCs.

Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach.

PURPOSE: Atherosclerotic plaque development and progression signifies a complex inflammatory disease mediated by a multitude of proinflammatory leukocyte subsets. Using single photon emission computed tomography (SPECT) coupled with computed tomography (CT), this study tested a new dual-isotope acquisition protocol to assess each radiotracer's capability to identify plaque phenotype and inflammation levels pertaining to leukocytes expressing leukocyte function-associated antigen-1 (LFA-1) and the leukocyte subset of proinflammatory macrophages expressing somatostatin receptor subtype-2 (SST2). Individual radiotracer uptake was quantified and the presence of corresponding immunohistological cell markers was assessed. METHODS: Human symptomatic carotid plaque segments were obtained from endarterectomy. Segments were incubated in dual-isotope radiotracers [111In]In-DOTA-butylamino-NorBIRT ([111In]In-Danbirt) and [99mTc]Tc-[N0-14,Asp0,Tyr3]-octreotate ([99mTc]Tc-Demotate 2) before scanning with SPECT/CT. Plaque phenotype was classified as pathological intimal thickening, fibrous cap atheroma or fibrocalcific using histology sections based on distinct morphological characteristics. Plaque segments were subsequently immuno-stained with LFA-1 and SST2 and quantified in terms of positive area fraction and compared against the corresponding SPECT images. RESULTS: Focal uptake of co-localising dual-radiotracers identified the heterogeneous distribution of inflamed regions in the plaques which co-localised with positive immuno-stained regions of LFA-1 and SST2. [111In]In-Danbirt and [99mTc]Tc-Demotate 2 uptake demonstrated a significant positive correlation (r = 0.651; p = 0.001). Fibrous cap atheroma plaque phenotype correlated with the highest [111In]In-Danbirt and [99mTc]Tc-Demotate 2 uptake compared with fibrocalcific plaques and pathological intimal thickening phenotypes, in line with the immunohistological analyses. CONCLUSION: A dual-isotope acquisition protocol permits the imaging of multiple leukocyte subsets and the pro-inflammatory macrophages simultaneously in atherosclerotic plaque tissue. [111In]In-Danbirt may have added value for assessing the total inflammation levels in atherosclerotic plaques in addition to classifying plaque phenotype.

Combined Application of Albumin-Binding [177Lu]Lu-PSMA-ALB-56 and Fast-Cleared PSMA Inhibitors: Optimization of the Pharmacokinetics.

The strategy of using radioligands for targeting the prostate-specific membrane antigen (PSMA) revealed to be promising for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Recently developed albumin-binding PSMA radioligands showed a remarkably increased tumor uptake because of the enhanced blood circulation, but higher accumulation of activity was also observed in off-target organs and tissues. The aim of this study was to investigate the option of using fast-cleared, small-molecular-weight PSMA inhibitors (PSMA-11, 2-PMPA, and ZJ-43) to reduce the kidney uptake of [177Lu]Lu-PSMA-ALB-56, a previously developed albumin-binding PSMA radioligand. Dual-isotope SPECT/CT imaging was performed with tumor-bearing mice coinjected with [177Lu]Lu-PSMA-ALB-56 and a 2.5-fold molar excess of [67Ga]Ga-PSMA-11. At early timepoints after injection, the high renal uptake of [67Ga]Ga-PSMA-11 reduced the accumulation of [177Lu]Lu-PSMA-ALB-56 in the kidneys substantially, whereas the tumor uptake of [177Lu]Lu-PSMA-ALB-56 was only slightly affected. These findings were confirmed in biodistribution studies, which revealed reduced uptake of [177Lu]Lu-PSMA-ALB-56 in the kidneys due to coadministered unlabeled PSMA-11 (9.1 ± 0.8% IA/g vs 46 ± 11% IA/g; 1 h p.i.). The tumor uptake of [177Lu]Lu-PSMA-ALB-56 was almost the same at 1 h p.i., irrespective of whether or not PSMA-11 was coinjected (24 ± 6% IA/g vs 27 ± 7% IA/g). The application of [177Lu]Lu-PSMA-ALB-56 with 2-PMPA or ZJ-43, respectively, showed similar results in biodistribution studies. Among all three tested PSMA inhibitors, 2-PMPA, applied at a 2.5-fold molar excess relative to [177Lu]Lu-PSMA-ALB-56, was most effective to improve the tumor-to-kidney ratios over the first hours after injection of [177Lu]Lu-PSMA-ALB-56. The concept of using a PSMA inhibitor together with [177Lu]Lu-PSMA-ALB-56 appears promising in view of a clinical translation of this and possibly other long-circulating PSMA radioligands.

Feasibility of simultaneous dual isotope acquisition for myocardial perfusion imaging with a cadmium zinc telluride camera.

BACKGROUND: We studied the impact of technetium-99m (99mTc) in the thallium-201 (201Tl) energy window (70 keV) to determine if CZT cardiac cameras allow us to perform simultaneous dual-isotope acquisition for myocardial perfusion imaging. METHODS: We included 117 consecutive patients. We injected 0.7 MBq/kg of 201Tl at stress, performed the first scan (image T1), then injected at rest 2 MBq/kg of 99mTc-tetrofosmin and immediately acquired a second scan with reconstruction in the energy window of thallium (image T2). A corrected thallium image was created by the subtraction of 99mTc downscattered photons (image TS). We compared spectra, image quality, and semiquantitative scores on T1, T2, and TS images. RESULTS: Though T2 images were of worse quality, TS images were of equal quality compared to T1 images in most cases. Scores show an underestimation of abnormalities in 20% of patients on T2 images and in 10% on TS images. CONCLUSIONS: Despite the improved energy resolution of CZT cameras, downscatter of technetium in the 201Tl window leads to an underestimation of the pathological territory in 10% to 20% of cases. It does not allow us to use simultaneous dual-isotope acquisition in clinical practice without additional tools for scatter correction.

Co-ingestion of Black Tea Reduces the Indispensable Amino Acid Digestibility of Hens' Egg in Indian Adults.

BACKGROUND: Tea, a commonly consumed beverage, contains high amounts of polyphenols that can impair protein digestibility, as demonstrated in vitro. There are no human studies examining the inhibitory influence of tea polyphenols (TPP) on high-quality protein digestibility. OBJECTIVE: The aim of this study was to determine the effect of black tea on the true indispensable amino acid (IAA) digestibility of whole boiled egg protein, in healthy adult humans, through use of a dual isotope tracer approach. METHODS: The effect of black TPP (4.6 mg/mL, ingested as a beverage with the meal) on 2H-labeled whole boiled egg protein, administered with ghee rice and tomato curry, was measured with reference to 13C-spirulina protein in healthy Indian adults aged 20-27 y of both sexes with BMI of 22.0 ± 2.8 kg/m2. The results were then compared to previously determined whole egg mean IAA digestibility measured by the same method, without black tea, in the same subjects (n = 5). To correct for any independent effect of TPP on spirulina protein (used as a standard protein), the true IAA digestibility of 13C-spirulina protein was independently measured with reference to a 2H-amino acid mixture, with and without co-ingestion of black tea, in 3 of the same subjects. RESULTS: The true IAA digestibility of whole boiled egg protein significantly decreased by 17% when co-ingested with black tea. However, there was no significant reduction in the true IAA digestibility of spirulina protein when co-ingested with black tea. CONCLUSIONS: TPP protein interactions reduced whole egg digestibility in healthy Indian adults but had minimal effect on spirulina protein digestibility. In populations who are at risk of dietary quality protein inadequacy, the consumption of tea during or after a meal can further increase the risk of inadequacy. This trial was registered at Clinical Trials Registry of India (http://ctri.nic.in) as CTRI/2018/03/012265.

Diagnostic value of stress thallium-201/rest technetium-99m-sestamibi sequential dual isotope high-speed myocardial perfusion imaging for the detection of haemodynamically relevant coronary artery stenosis.

BACKGROUND: The aim of this study was to determine the diagnostic accuracy of stress thallium-201/rest technetium-99m-sestamibi sequential dual-isotope high-speed myocardial perfusion imaging (DI-HS-MPI) against invasively determined fractional flow reserve (FFR). METHODS: Fifty-four consecutive patients prospectively underwent DI-HS-MPI before invasive coronary angiography. Perfusion was scored visually by summed stress score on a patient and coronary territory basis. Significant coronary artery disease (CAD) was defined by the presence of ≥ 90% stenosis/occlusion or fractional flow reserve ≤ 0.80 for coronary stenosis ≥ 50%. RESULTS: FFR was measured in 69 of 162 coronary vessels, with 1.28 ± 0.56 vessels assessed/patient. Sensitivity, specificity, and diagnostic accuracy of MPI for the detection of significant CAD were 92.8%, 69.2%, and 81.4%, on a patient basis, and 83.7%, 90.4%, and 88.8% by coronary territory. CONCLUSIONS: DI-HS-MPI accurately detects functionally significant CAD as defined by using FFR.

Low-dose dual-isotope procedure planed for myocardial perfusion CZT-SPECT and assessed through a head-to-head comparison with a conventional single-isotope protocol.

PURPOSE OF THE REPORT: This study aimed at assessing an original low-dose dual-isotope procedure in which the abnormal stress Tc-99m Sestamibi SPECT is followed by rest Tl-201 SPECT, along with a head-to-head comparison with a single-isotope procedure. METHODS AND RESULTS: One hundred two patients, referred for a low-dose stress-SPECT with Sestamibi (123 ± 20 MBq) on a CZT camera and for whom a rest Sestamibi SPECT was warranted, had an additional Tl-201 rest-SPECT (52 ± 5 MBq) between stress and rest Sestamibi SPECT recordings. Tl-201 images were processed for spill-over and scatter corrections, and uptake differences with stress Sestamibi SPECT were analyzed: (1) for rest acquisitions from Tl-201 (dual-isotope procedure) and from Sestamibi (single-isotope procedure) and (2) in segments for which a diagnosis of ischemia, infarct, or normal perfusion was achieved. Mean effective dose was 8.3 mSv for dual-isotope but would decrease to 5.7 mSv for an expected rate of 37% of patients for whom rest-SPECT is not warranted. After a further background correction of Tl-201 images, the rest-stress difference in myocardial uptake was equivalent between dual- and single-procedures for identifying ischemic segments (respective areas-under-curves: 0.83 ± 0.03 and 0.81 ± 0.03). CONCLUSION: This original dual-isotope procedure provides acceptable radiation doses and consistent results, as compared with conventional single-isotope.

First assessment of simultaneous dual isotope (123I/99mTc) cardiac SPECT on two different CZT cameras: A phantom study.

BACKGROUND: We studied the impact of simultaneous dual-isotope acquisition on 123I/99mTc mismatch assessment using two CZT cameras (DNM 530c, GE Healthcare and DSPECT, Biosensors International). METHODS: We used an anthropomorphic torso phantom (respectively filled with a solution of 123I alone, 99mTc alone, and a mixture of 123I and 99mTc) and its cardiac insert with two defects mimicking two matched and mismatched defects. Mismatch extent and reconstructed image contrast were evaluated. RESULTS: The acquisition mode (single vs dual) significantly impacted (i) 99mTc (but not 123I) reconstructed segmental activities using both camera (P < .001), and (ii) image contrast (using 123I and DNM 530c, P < .0001; and using both 123I and 99mTc with DSPECT, P < .0001). However, the defect and mismatch size were not impacted by the type of acquisition. With both DNM 530c and DSPECT, Lin's concordance correlation coefficient and Bland-Altman analysis demonstrated an almost perfect concordance and agreement between single- and simultaneous dual-isotope segmental activity (123I and 99mTc). CONCLUSIONS: This study found no impact of the acquisition mode (single vs dual) or the type of camera (DSPECT vs DNM 530c) on 123I and 99mTc defect size and mismatch, providing a new step toward simultaneous dual-isotope acquisition for combined innervation and perfusion assessment.

Relationships between left ventricular sympathetic innervation and diastolic dysfunction: the role of myocardial innervation/perfusion mismatch.

BACKGROUND: A possible relationship between cardiac sympathetic denervation and left ventricular (LV) diastolic dysfunction has been suggested. However, an evaluation of the interactions between myocardial adrenergic tone and LV perfusion and diastolic function is lacking. METHODS AND RESULTS: Seventy-two patients underwent 99mTc-tetrofosmin/123I-metaiodobenzylguanidine (123I-MIBG) cardiac Cadmium-Zinc-Telluride (CZT) imaging. The summed rest score (SRS) and summed 123I-MIBG score (SS-MIBG) were computed as measures of regional perfusion and innervation heterogeneities. LV segments showing an impaired innervation, despite a relatively preserved perfusion (99mTc-tetrofosmin-123I-MIBG tracers' uptake ≥25%), were individuated (innervation/perfusion mismatch). The peak filling rate (PFR) was computed as a measure of LV diastolic function. Nineteen of the 72 (26%) patients presented a normal LV diastolic function, while 29 (40%) and 24 (34%) had a mild and overt diastolic dysfunction. Subjects with diastolic dysfunction showed more abnormal SRS and SS-MIBG values (P < 0.001). In the global population, 502/1224 (41%) LV segments showed an innervation/perfusion mismatch. A modest correlation between the extent of cardiac innervation/perfusion mismatch and PFR values was evident (R = -0.27, P = 0.029). On multivariate analysis, the extent of regional innervation/perfusion mismatch remained an independent predictor of overt LV diastolic abnormalities (P = 0.017). CONCLUSIONS: The burden of LV regions showing an innervation/perfusion mismatch associates with the occurrence of overt diastolic dysfunction.

Diagnostic Performance of the Simultaneous Acquisition Rest 99 mTc-Tetrofosmin/Stress 201Tl Dual-Isotope Protocol With a Semiconductor Camera　- Comparison With the Rest-Stress 99 mTc-Tetrofosmin Protocol.

BACKGROUND: This study compared the diagnostic value of myocardial perfusion imaging (MPI) between the rest-stress 99 mTc-tetrofosmin protocol (Tc/Tc protocol) and simultaneous acquisition rest 99 mTc-tetrofosmin/stress 201Tl dual-isotope protocol (SDI protocol) with a semiconductor camera.Methods and Results: We retrospectively studied 147 patients who underwent stress MPI using a cadmium-zinc-telluride camera and invasive coronary angiography within a 3-month interval. The Tc/Tc and SDI protocols were used in 59 and 88 patients, respectively. The sensitivity, specificity, and accuracy of the summed difference score in per-patient analysis were 56%, 85%, and 69%, respectively, for the Tc/Tc protocol and 89%, 82%, and 85%, respectively, for the SDI protocol. The area under the receiver operating characteristic curve was significantly better for the SDI than Tc/Tc protocol for the left anterior descending artery (0.836 vs. 0.674; P=0.0380), the left circumflex artery (0.754 vs. 0.599; P=0.0441), and in per-patient analysis (0.875 vs. 0.707; P=0.0135). There was no significant difference in the diagnostic accuracy of the summed stress score for any vessel or in per-patient analysis between the 2 protocols. CONCLUSIONS: The SDI protocol had a higher diagnostic accuracy for the detection of coronary ischemia than the Tc/Tc protocol.