High-temporal resolution functional PET/MRI reveals coupling between human metabolic and hemodynamic brain response.

PURPOSE: Positron emission tomography (PET) provides precise molecular information on physiological processes, but its low temporal resolution is a major obstacle. Consequently, we characterized the metabolic response of the human brain to working memory performance using an optimized functional PET (fPET) framework at a temporal resolution of 3 s. METHODS: Thirty-five healthy volunteers underwent fPET with [18F]FDG bolus plus constant infusion, 19 of those at a hybrid PET/MRI scanner. During the scan, an n-back working memory paradigm was completed. fPET data were reconstructed to 3 s temporal resolution and processed with a novel sliding window filter to increase signal to noise ratio. BOLD fMRI signals were acquired at 2 s. RESULTS: Consistent with simulated kinetic modeling, we observed a constant increase in the [18F]FDG signal during task execution, followed by a rapid return to baseline after stimulation ceased. These task-specific changes were robustly observed in brain regions involved in working memory processing. The simultaneous acquisition of BOLD fMRI revealed that the temporal coupling between hemodynamic and metabolic signals in the primary motor cortex was related to individual behavioral performance during working memory. Furthermore, task-induced BOLD deactivations in the posteromedial default mode network were accompanied by distinct temporal patterns in glucose metabolism, which were dependent on the metabolic demands of the corresponding task-positive networks. CONCLUSIONS: In sum, the proposed approach enables the advancement from parallel to truly synchronized investigation of metabolic and hemodynamic responses during cognitive processing. This allows to capture unique information in the temporal domain, which is not accessible to conventional PET imaging.

Quantification and Characterization of Fine Plastic Particles as Considerable Components in Atmospheric Fine Particles.

The negative effects of air pollution, especially fine particulate matter (PM2.5, particles with an aerodynamic diameter of ≤2.5 µm), on human health, climate, and ecosystems are causing significant concern. Nevertheless, little is known about the contributions of emerging pollutants such as plastic particles to PM2.5 due to the lack of continuous measurements and characterization methods for atmospheric plastic particles. Here, we investigated the levels of fine plastic particles (FPPs) in PM2.5 collected in urban Shanghai at a 2 h resolution by using a novel versatile aerosol concentration enrichment system that concentrates ambient aerosols up to 10-fold. The FPPs were analyzed offline using the combination of spectroscopic and microscopic techniques that distinguished FPPs from other carbon-containing particles. The average FPP concentrations of 5.6 µg/m3 were observed, and the ratio of FPPs to PM2.5 was 13.2% in this study. The FPP sources were closely related to anthropogenic activities, which pose a potential threat to ecosystems and human health. Given the dramatic increase in plastic production over the past 70 years, this study calls for better quantification and control of FPP pollution in the atmosphere.

Left Ventricular Strain Measurements Derived from MR Feature Tracking: A Head-to-Head Comparison of a Higher Temporal Resolution Method With a Conventional Method.

BACKGROUND: Magnetic resonance feature tracking (MR-FT) is an imaging technique that quantifies both global and regional myocardial strain. Currently, conventional MR-FT provides a superior signal and contrast-to-noise ratio but has a relatively low temporal resolution. A higher temporal resolution MR-FT technique may provide improved results. PURPOSE: To explore the impact of higher temporal resolution on left ventricular (LV) myocardial strain measurements using MR-FT. STUDY TYPE: Prospective. POPULATION: One hundred and fifty-three participants including five healthy subjects and patients with various cardiac diseases referred to MR for cardiac assessment. FIELD STRENGTH: 3 T, balanced steady-state free precession sequence with and without compressed sensing (temporal resolution: 10 msec and 40 msec, respectively). ASSESSMENT: Conventional (40 msec) and higher (10 msec) temporal resolution data were acquired in all subjects during the same scanning session. Global circumferential strain (GCS), global longitudinal strain (GLS), and global radial strain (GRS) as well as peak systolic and diastolic strain rates (SRs) were measured by MR-FT and compared between the two temporal resolutions. We also performed subgroup analyses according to heart rates (HRs) and LV ejection fraction (LVEF). STATISTICAL TESTS: Paired t-test, Wilcoxon signed-rank test, linear regression analyses, Bland-Altman plots. A P value <0.05 was considered to be statistically significant. RESULTS: GCS and GRS were significantly higher in the 10-msec temporal resolution studies compared to the 40-msec temporal resolution studies (GCS: -13.00 ± 6.58% vs. -12.51 ± 5.76%; GRS: 21.97 ± 14.54% vs. 20.62 ± 12.52%). In the subgroup analyses, significantly higher GLS, GCS, and GRS values were obtained in subjects with LVEF ≥50%, and significantly higher GCS and GRS values were obtained in subjects with HRs <70 bpm when assessed with the 10-msec vs. the 40-msec temporal resolutions. All the peak systolic and diastolic SRs were significantly higher in the higher temporal resolution acquisitions. This was also true for all subgroups. DATA CONCLUSIONS: Higher temporal resolution resulted in significantly higher cardiac strain and SR values using MR-FT and could be beneficial, particularly in patients with LVEF ≥50% and HR <70 bpm. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Sub-millisecond 2D MRI of the vocal fold oscillation using single-point imaging with rapid encoding.

OBJECTIVE: The slow spatial encoding of MRI has precluded its application to rapid physiologic motion in the past. The purpose of this study is to introduce a new fast acquisition method and to demonstrate feasibility of encoding rapid two-dimensional motion of human vocal folds with sub-millisecond resolution. METHOD: In our previous work, we achieved high temporal resolution by applying a rapidly switched phase encoding gradient along the direction of motion. In this work, we extend phase encoding to the second image direction by using single-point imaging with rapid encoding (SPIRE) to image the two-dimensional vocal fold oscillation in the coronal view. Image data were gated using electroglottography (EGG) and motion corrected. An iterative reconstruction with a total variation (TV) constraint was used and the sequence was also simulated using a motion phantom. RESULTS: Dynamic images of the vocal folds during phonation at pitches of 150 and 165 Hz were acquired in two volunteers and the periodic motion of the vocal folds at a temporal resolution of about 600 µs was shown. The simulations emphasize the necessity of SPIRE for two-dimensional motion encoding. DISCUSSION: SPIRE is a new MRI method to image rapidly oscillating structures and for the first time provides dynamic images of the vocal folds oscillations in the coronal plane.

Multi-step ahead prediction of hourly influent characteristics for wastewater treatment plants: a case study from North America.

Prediction of influent characteristics, before any treatment takes place, is of great importance to the operation and management of wastewater treatment plants (WWTPs). In this study, four machine-learning models, including multilayer perceptron (MLP), long short-term memory network (LSTM), K-nearest neighbour (KNN), and random forest (RF), are introduced to utilize real-time wastewater data from three WWTPs in North America (i.e., Tres Rios, Woodward, and one confidential plant) for predicting hourly influent characteristics. Input variables are selected using an autocorrelation analysis and a variable importance measure from RF. Both univariate and multivariate analyses are investigated to improve model accuracy. The performances of one- and multiple-step-ahead models are compared. With a short prediction horizon, all the models derived from both univariate and multivariate analyses show excellent performance. It was found that the performance deterioration as the prediction horizon expands could be mitigated significantly by including extra variables, such as meteorological variables. This work can provide valuable support for the high-temporal-resolution prediction of wastewater influent characteristics for WWTPs. The proposed models can also bridge the gap between data and decision-making in the wastewater sector.

Magnetic resonance imaging of the vocal fold oscillations with sub-millisecond temporal resolution.

PURPOSE: The temporal resolution of the MRI acquisition is intrinsically limited by the duration of the spatial encoding, which is typically on the order of milliseconds. Faster motion such as the vibration of the vocal folds during phonation cannot be imaged with conventional MRI as this would require sampling frequencies in the kilo-Hertz range. Here, a faster MRI acquisition strategy is presented that encodes a 1D periodic motion at a temporal resolution that is an order of magnitude higher compared to conventional MRI. METHODS: The proposed method encodes the position of an object moving along 1 dimension by applying very short phase encoding gradients along the same direction. This reduces the temporal resolution from the repetition time (TR) to the duration of the phase encoding gradients, which in this work was well below 1 ms. The technique is applied to the vocal fold oscillations and the position of the vocal folds is measured simultaneously using electroglottography (EGG). Simulations of the point spread function for regular encoding and the proposed method are performed as well. RESULTS: With this new phase, encoding strategy oscillations of the human vocal folds up to a frequency of 145 Hz could be dynamically imaged at 10 images per cycle. Simulations show the advantage of this method over conventional imaging of fast moving objects. CONCLUSION: A new method for MR imaging of fast moving spins is presented allowing a temporal resolution below 1 ms at a spatial resolution below 1 mm, circumventing TR as the limit for temporal resolution.

Approaches to Exploring Spatio-Temporal Surface Dynamics in Nanoparticles with In Situ Transmission Electron Microscopy.

Many nanoparticles in fields such as heterogeneous catalysis undergo surface structural fluctuations during chemical reactions, which may control functionality. These dynamic structural changes may be ideally investigated with time-resolved in situ electron microscopy. We have explored approaches for extracting quantitative information from large time-resolved image data sets with a low signal to noise recorded with a direct electron detector on an aberration-corrected transmission electron microscope. We focus on quantitatively characterizing beam-induced dynamic structural rearrangements taking place on the surface of CeO2 (ceria). A 2D Gaussian fitting procedure is employed to determine the position and occupancy of each atomic column in the nanoparticle with a temporal resolution of 2.5 ms and a spatial precision of 0.25 Å. Local rapid lattice expansions/contractions and atomic migration were revealed to occur on the (100) surface, whereas (111) surfaces were relatively stable throughout the experiment. The application of this methodology to other materials will provide new insights into the behavior of nanoparticle surface reconstructions that were previously inaccessible using other methods, which will have important consequences for the understanding of dynamic structure-property relationships.

A functional form for a representative individual arterial input function measured from a population using high temporal resolution DCE MRI.

PURPOSE: To measure the arterial input function (AIF), an essential component of tracer kinetic analysis, in a population of patients using an optimized dynamic contrast-enhanced (DCE) imaging sequence and to estimate inter- and intrapatient variability. From these data, a representative AIF that may be used for realistic simulation studies can be extracted. METHODS: Thirty-nine female patients were imaged on multiple visits before and during a course of neoadjuvant chemotherapy for breast cancer. A total of 97 T1 -weighted DCE studies were analyzed including bookend estimates of T1 and model-fitting to each individual AIF. Area under the curve and cardiac output were estimated from each first pass peak, and these data were used to assess inter- and intrapatient variability of the AIF. RESULTS: Interpatient variability exceeded intrapatient variability of the AIF. There was no change in cardiac output as a function of MR visit (mean value 5.6 ± 1.1 L/min) but baseline blood T1 increased significantly following the start of chemotherapy (which was accompanied by a decrease in hematocrit). CONCLUSION: The AIF in an individual patient can be measured reproducibly but the variability of AIFs between patients suggests that use of a population AIF will decrease the precision of tracer kinetic analysis performed in cross-patient comparison studies. A representative AIF is presented that is typical of the population but retains the characteristics of an individually measured AIF.

Feasibility of quantitative regional ventilation and perfusion mapping with phase-resolved functional lung (PREFUL) MRI in healthy volunteers and COPD, CTEPH, and CF patients.

PURPOSE: In this feasibility study, a phase-resolved functional lung imaging postprocessing method for extraction of dynamic perfusion (Q) and ventilation (V) parameters using a conventional 1H lung MRI Fourier decomposition acquisition is introduced. METHODS: Time series of coronal gradient-echo MR images with a temporal resolution of 288 to 324 ms of two healthy volunteers, one patient with chronic thromboembolic hypertension, one patient with cystic fibrosis, and one patient with chronic obstructive pulmonary disease were acquired at 1.5 T. Using a sine model to estimate cardiac and respiratory phases of each image, all images were sorted to reconstruct full cardiac and respiratory cycles. Time to peak (TTP), V/Q maps, and fractional ventilation flow-volume loops were calculated. RESULTS: For the volunteers, homogenous ventilation and perfusion TTP maps (V-TTP, Q-TTP) were obtained. The chronic thromboembolic hypertension patient showed increased perfusion TTP in hypoperfused regions in visual agreement with dynamic contrast-enhanced MRI, which improved postpulmonary endaterectomy surgery. Cystic fibrosis and chronic obstructive pulmonary disease patients showed a pattern of increased V-TTP and Q-TTP in regions of hypoventilation and decreased perfusion. Fractional ventilation flow-volume loops of the chronic obstructive pulmonary disease patient were smaller in comparison with the healthy volunteer, and showed regional differences in visual agreement with functional small airways disease and emphysema on CT. CONCLUSIONS: This study shows the feasibility of phase-resolved functional lung imaging to gain quantitative information regarding regional lung perfusion and ventilation without the need for ultrafast imaging, which will be advantageous for future clinical translation. Magn Reson Med 79:2306-2314, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Estimating breast tumor blood flow during neoadjuvant chemotherapy using interleaved high temporal and high spatial resolution MRI.

PURPOSE: To evaluate an interleaved MRI sampling strategy that acquires both high temporal resolution (HTR) dynamic contrast-enhanced (DCE) data for quantifying breast tumor blood flow (TBF) and high spatial resolution (HSR) DCE data for clinical reporting, following a single standard injection of contrast agent. METHODS: A simulation study was used to evaluate the performance of the interleaved technique under different conditions. In a prospective clinical study, 18 patients with primary breast cancer, who were due to undergo neoadjuvant chemotherapy (NACT), were examined using interleaved HTR and HSR DCE-MRI at 1.5 Tesla. Tumor regions of interest were analyzed with a two-compartment tracer kinetic model. Paired parameters (n = 10) from the data acquired before and post-cycle 2 of NACT were compared using the nonparametric Wilcoxon signed-rank test. RESULTS: Simulations demonstrated that TBF was reliably estimated using the proposed strategy. The region of interest analysis revealed significant changes in TBF (0.81-0.43 mL/min/mL; P = 0.002) following two cycles of NACT. The HSR data were reported in the normal way and enabled the assessment of tumor volume, which decreased by 53% following NACT (P = 0.065). CONCLUSIONS: TBF can be measured reliably using the proposed strategy without compromising a standard clinical protocol. Furthermore, in our feasibility study, TBF decreased significantly following NACT, whereas capillary permeability surface-area product did not. Magn Reson Med 79:317-326, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

[Optimization of Scan Parameters for Patient without Breath Hold in Chest by Computed Tomography].

This study aims to establish optimal scan parameters by high temporal resolution computed tomography (CT) scan for emergency patients who cannot hold their breath. First, we investigated scan parameters that can reduce the effect of motion by evaluating motion artifacts from the moving phantom scan and the temporal sensitivity profile (TPS) measurement. Second, we confirmed the standard deviation (SD) of the CT values as well as the operating time and exposure dose. As the results, plan C [rotation time: 0.275 s, detector rows: 80, pitch factor (PF): 1.100] and plan E (rotation time: 0.275 s, detector rows: 100, PF: 0.880) demonstrated high temporal resolution. The difference between the two is PF. The noise of plan C increased because PF is higher than plan E. This is also evident from the results of SD measurement. Our study demonstrates that the optimal parameters for patients who cannot hold their breath in the emergency care are plan C and plan E. In conclusion, we clarified necessary optimal scan parameters to provide clinical image that has more diagnostic information by reducing the effect of breath motion for emergency patients.

Direct comparison of high-temporal-resolution CINE MRI with Doppler ultrasound for assessment of diastolic dysfunction in mice.

Diastolic dysfunction is a sensitive early indicator of heart failure and can provide additional data to conventional measures of systolic function. Transmitral Doppler ultrasound, which measures the one-dimensional flow of blood through the mitral valve, is currently the preferred method for the measurement of diastolic function, but the measurement of the left ventricular volume changes using high-temporal-resolution cinematic magnetic resonance imaging (CINE MRI) is an alternative approach which is emerging as a potentially more robust and user-independent technique. Here, we investigated the performance of high-temporal-resolution CINE MRI and compared it with ultrasound for the detection of diastolic dysfunction in a mouse model of myocardial infarction. An in-house, high-temporal-resolution, retrospectively gated CINE sequence was developed with a temporal resolution of 1 ms. Diastolic function in mice was assessed using a custom-made, open-source reconstruction package. Early (E) and late (A) left ventricular filling phases were easily identifiable, and these measurements were compared directly with high-frequency, pulsed-wave, Doppler ultrasound measurements of mitral valve inflow. A repeatability study established that high-temporal-resolution CINE MRI and Doppler ultrasound showed comparable accuracy when measuring E/A in normal control mice. However, when applied in a mouse model of myocardial infarction, high-temporal-resolution CINE MRI indicated diastolic heart failure (E/A = 0.94 ± 0.11), whereas ultrasound falsely detected normal cardiac function (E/A = 1.21 ± 0.11). The addition of high-temporal-resolution CINE MRI to preclinical imaging studies enhances the library of sequences available to cardiac researchers and potentially identifies diastolic heart failure early in disease progression.

Comparison of conventional DCE-MRI and a novel golden-angle radial multicoil compressed sensing method for the evaluation of breast lesion conspicuity.

PURPOSE: To compare a novel multicoil compressed sensing technique with flexible temporal resolution, golden-angle radial sparse parallel (GRASP), to conventional fat-suppressed spoiled three-dimensional (3D) gradient-echo (volumetric interpolated breath-hold examination, VIBE) MRI in evaluating the conspicuity of benign and malignant breast lesions. MATERIALS AND METHODS: Between March and August 2015, 121 women (24-84 years; mean, 49.7 years) with 180 biopsy-proven benign and malignant lesions were imaged consecutively at 3.0 Tesla in a dynamic contrast-enhanced (DCE) MRI exam using sagittal T1-weighted fat-suppressed 3D VIBE in this Health Insurance Portability and Accountability Act-compliant, retrospective study. Subjects underwent MRI-guided breast biopsy (mean, 13 days [1-95 days]) using GRASP DCE-MRI, a fat-suppressed radial "stack-of-stars" 3D FLASH sequence with golden-angle ordering. Three readers independently evaluated breast lesions on both sequences. Statistical analysis included mixed models with generalized estimating equations, kappa-weighted coefficients and Fisher's exact test. RESULTS: All lesions demonstrated good conspicuity on VIBE and GRASP sequences (4.28 ± 0.81 versus 3.65 ± 1.22), with no significant difference in lesion detection (P = 0.248). VIBE had slightly higher lesion conspicuity than GRASP for all lesions, with VIBE 12.6% (0.63/5.0) more conspicuous (P < 0.001). Masses and nonmass enhancement (NME) were more conspicuous on VIBE (P < 0.001), with a larger difference for NME (14.2% versus 9.4% more conspicuous). Malignant lesions were more conspicuous than benign lesions (P < 0.001) on both sequences. CONCLUSION: GRASP DCE-MRI, a multicoil compressed sensing technique with high spatial resolution and flexible temporal resolution, has near-comparable performance to conventional VIBE imaging for breast lesion evaluation. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;45:1746-1752.

High-Temporal-Resolution High-Spatial-Resolution Spaceborne SAR Based on Continuously Varying PRF.

Synthetic Aperture Radar (SAR) is a well-established and powerful imaging technique for acquiring high-spatial-resolution images of the Earth's surface. With the development of beam steering techniques, sliding spotlight and staring spotlight modes have been employed to support high-spatial-resolution applications. In addition to this strengthened high-spatial-resolution and wide-swath capability, high-temporal-resolution (short repeat-observation interval) represents a key capability for numerous applications. However, conventional SAR systems are limited in that the same patch can only be illuminated for several seconds within a single pass. This paper considers a novel high-squint-angle system intended to acquire high-spatial-resolution spaceborne SAR images with repeat-observation intervals varying from tens of seconds to several minutes within a single pass. However, an exponentially increased range cell migration would arise and lead to a conflict between the receive window and 'blind ranges'. An efficient data acquisition technique for high-temporal-resolution, high-spatial-resolution and high-squint-angle spaceborne SAR, in which the pulse repetition frequency (PRF) is continuously varied according to the changing slant range, is presented in this paper. This technique allows echo data to remain in the receive window instead of conflicting with the transmitted pulse or nadir echo. Considering the precision of hardware, a compromise and practical strategy is also proposed. Furthermore, a detailed performance analysis of range ambiguities is provided with respect to parameters of TerraSAR-X. For strong point-like targets, the range ambiguity of this technique would be better than that of uniform PRF technique. For this innovative technique, a resampling strategy and modified imaging algorithm have been developed to handle the non-uniformly sampled echo data. Simulations are performed to validate the efficiency of the proposed technique and the associated imaging algorithm.

Estimation of tile drainage contribution to streamflow and nutrient loads at the watershed scale based on continuously monitored data.

Nitrogen losses from artificially drained watersheds degrade water quality at local and regional scales. In this study, we used an end-member mixing analysis (EMMA) together with high temporal resolution water quality and streamflow data collected in the 122 km2 Otter Creek watershed located in northeast Iowa. We estimated the contribution of three end-members (groundwater, tile drainage, and quick flow) to streamflow and nitrogen loads and tested several combinations of possible nitrate concentrations for the end-members. Results indicated that subsurface tile drainage is responsible for at least 50% of the watershed nitrogen load between April 15 and November 1, 2015. Tiles delivered up to 80% of the stream N load while providing only 15-43% of the streamflow, whereas quick flows only marginally contributed to N loading. Data collected offer guidance about areas of the watershed that should be targeted for nitrogen export mitigation strategies.

A microdialysis and enzymatic reactor sensing procedure for the simultaneous registration of online glutamate measurements at high temporal resolution during epileptiform activity.

Glutamate measurement in microdialysis samples has primarily been determined using HPLC methods, and several attempts have been made to establish a relationship between this neurotransmitter and EEG activity during altered brain function, such as epilepsy. However, classic microdialysis methods lack high temporal resolution. In this study, a new alternative is proposed to improve the time resolution and thus obtain a better understanding of the dynamics of Glu and its relationship with epileptiform activity. A new setup was designed to measure Glu online in microdialysates using enzymatic reactors and fluorescence detection. In this study, we performed EEG recordings and Glu measurements simultaneously in the hippocampus to establish their relationship with the epileptiform events that are induced by pentylenetetrazole in intact and epileptic rats. Basal Glu levels in intact and animals with spontaneous seizures were not significantly different. However, a significant increase in Glu levels was detected during the first pentylenetetrazole-induced seizure in both groups. EEG analysis showed that the amplitude of epileptiform activity was higher in rats with spontaneous seizures and that the frequency of this activity did not change. The results showed that this method can be used to determine Glu changes at high temporal resolution and that these changes can be related to seizure activity. In addition, this method can also be used to measure other neurotransmitters that generate fluorescent derivatives. Moreover, this new technique has the following advantages compared with classical neurochemical methods: easy setup, low training requirements, no need for separation, rapidity, and the experimental data can be obtained and analysis performed in a single session.

Sequential evolution of cortical activity and effective connectivity of swallowing using fMRI.

Swallowing consists of a hierarchical sequence of primary motor and somatosensory processes. The temporal interplay of different phases is complex and clinical disturbances frequent. Of interest was the temporal interaction of the swallowing network. Time resolution optimized functional magnetic resonance imaging was used to describe the temporal sequence of representation sites of swallowing and their functional connectivity. Sixteen young healthy volunteers were investigated who swallowed 2 ml of water 20 times per run with a repetition time for functional imaging of 514 ms. After applying the general linear model approach to identify activation magnitude in preselected regions of interest repeated measures analysis of variance (rmANOVA) was used to detect relevant effects on lateralization, time, and onset. Furthermore, dynamic causal modeling (DCM) was applied to uncover where the input enters the model and the way in which the cortical regions are connected. The temporal analysis revealed a successive activation starting at the premotor cortex, supplementary motor area (SMA), and bilateral thalamus, followed by the primary sensorimotor cortex, the posterior insula, and cerebellum and culminating with activation in the pons shortly before subsiding. The rmANOVA revealed that activation was lateralized initially to the left hemisphere and gradually moved to the right hemisphere over time. The group random effects DCM analysis resulted in a most likely model that consisted of inputs to SMA and M1S1, bidirectionally connected, and a one-way connection from M1S1 to the posterior insula.

High-Temporal-Resolution Kinetic Modeling of Lung Tumors with Dual-Blood Input Function Using Total-Body Dynamic PET.

The lungs are supplied by both the pulmonary arteries carrying deoxygenated blood originating from the right ventricle and the bronchial arteries carrying oxygenated blood downstream from the left ventricle. However, this effect of dual blood supply has never been investigated using PET, partially because the temporal resolution of conventional dynamic PET scans is limited. The advent of PET scanners with a long axial field of view, such as the uEXPLORER total-body PET/CT system, permits dynamic imaging with high temporal resolution (HTR). In this work, we modeled the dual-blood input function (DBIF) and studied its impact on the kinetic quantification of normal lung tissue and lung tumors using HTR dynamic PET imaging. Methods: Thirteen healthy subjects and 6 cancer subjects with lung tumors underwent a dynamic 18F-FDG scan with the uEXPLORER for 1 h. Data were reconstructed into dynamic frames of 1 s in the early phase. Regional time-activity curves of lung tissue and tumors were analyzed using a 2-tissue compartmental model with 3 different input functions: the right ventricle input function, left ventricle input function, and proposed DBIF, all with time delay and dispersion corrections. These models were compared for time-activity curve fitting quality using the corrected Akaike information criterion and for differentiating lung tumors from lung tissue using the Mann-Whitney U test. Voxelwise multiparametric images by the DBIF model were further generated to verify the regional kinetic analysis. Results: The effect of dual blood supply was pronounced in the high-temporal-resolution time-activity curves of lung tumors. The DBIF model achieved better time-activity curve fitting than the other 2 single-input models according to the corrected Akaike information criterion. The estimated fraction of left ventricle input was low in normal lung tissue of healthy subjects but much higher in lung tumors (∼0.04 vs. ∼0.3, P < 0.0003). The DBIF model also showed better robustness in the difference in 18F-FDG net influx rate [Formula: see text] and delivery rate [Formula: see text] between lung tumors and normal lung tissue. Multiparametric imaging with the DBIF model further confirmed the differences in tracer kinetics between normal lung tissue and lung tumors. Conclusion: The effect of dual blood supply in the lungs was demonstrated using HTR dynamic imaging and compartmental modeling with the proposed DBIF model. The effect was small in lung tissue but nonnegligible in lung tumors. HTR dynamic imaging with total-body PET can offer a sensitive tool for investigating lung diseases.

Quantitative Total-Body Imaging of Blood Flow with High Temporal Resolution Early Dynamic 18F-Fluorodeoxyglucose PET Kinetic Modeling.

Quantitative total-body PET imaging of blood flow can be performed with freely diffusible flow radiotracers such as 15O-water and 11C-butanol, but their short half-lives necessitate close access to a cyclotron. Past efforts to measure blood flow with the widely available radiotracer 18F-fluorodeoxyglucose (FDG) were limited to tissues with high 18F-FDG extraction fraction. In this study, we developed an early-dynamic 18F-FDG PET method with high temporal resolution kinetic modeling to assess total-body blood flow based on deriving the vascular transit time of 18F-FDG and conducted a pilot comparison study against a 11C-butanol reference. Methods: The first two minutes of dynamic PET scans were reconstructed at high temporal resolution (60×1 s, 30×2 s) to resolve the rapid passage of the radiotracer through blood vessels. In contrast to existing methods that use blood-to-tissue transport rate ( K 1 ) as a surrogate of blood flow, our method directly estimates blood flow using a distributed kinetic model (adiabatic approximation to the tissue homogeneity model; AATH). To validate our 18F-FDG measurements of blood flow against a flow radiotracer, we analyzed total-body dynamic PET images of six human participants scanned with both 18F-FDG and 11C-butanol. An additional thirty-four total-body dynamic 18F-FDG PET scans of healthy participants were analyzed for comparison against literature blood flow ranges. Regional blood flow was estimated across the body and total-body parametric imaging of blood flow was conducted for visual assessment. AATH and standard compartment model fitting was compared by the Akaike Information Criterion at different temporal resolutions. Results: 18F-FDG blood flow was in quantitative agreement with flow measured from 11C-butanol across same-subject regional measurements (Pearson R=0.955, p<0.001; linear regression y=0.973x-0.012), which was visually corroborated by total-body blood flow parametric imaging. Our method resolved a wide range of blood flow values across the body in broad agreement with literature ranges (e.g., healthy cohort average: 0.51±0.12 ml/min/cm3 in the cerebral cortex and 2.03±0.64 ml/min/cm3 in the lungs, respectively). High temporal resolution (1 to 2 s) was critical to enabling AATH modeling over standard compartment modeling. Conclusions: Total-body blood flow imaging was feasible using early-dynamic 18F-FDG PET with high-temporal resolution kinetic modeling. Combined with standard 18F-FDG PET methods, this method may enable efficient single-tracer flow-metabolism imaging, with numerous research and clinical applications in oncology, cardiovascular disease, pain medicine, and neuroscience.

High-Temporal-Resolution Lung Kinetic Modeling Using Total-Body Dynamic PET with Time-Delay and Dispersion Corrections.

Tracer kinetic modeling in dynamic PET has the potential to improve the diagnosis, prognosis, and research of lung diseases. The advent of total-body PET systems with much greater detection sensitivity enables high-temporal-resolution (HTR) dynamic PET imaging of the lungs. However, existing models may become insufficient for modeling the HTR data. In this paper, we investigate the necessity of additional corrections to the input function for HTR lung kinetic modeling. Methods: Dynamic scans with HTR frames of as short as 1 s were performed on 13 healthy subjects with a bolus injection of about [Formula: see text] of 18F-FDG using the uEXPLORER total-body PET/CT system. Three kinetic models with and without time-delay and dispersion corrections were compared for the quality of lung time-activity curve fitting using the Akaike information criterion. The impact on quantification of 18F-FDG delivery rate [Formula: see text], net influx rate [Formula: see text] and fractional blood volume [Formula: see text] was assessed. Parameter identifiability analysis was also performed to evaluate the reliability of kinetic quantification with respect to noise. Correlation of kinetic parameters with age was investigated. Results: HTR dynamic imaging clearly revealed the rapid change in tracer concentration in the lungs and blood supply (i.e., the right ventricle). The uncorrected input function led to poor time-activity curve fitting and biased quantification in HTR kinetic modeling. The fitting was improved by time-delay and dispersion corrections. The proposed model resulted in an approximately 85% decrease in [Formula: see text], an approximately 75% increase in [Formula: see text], and a more reasonable [Formula: see text] (∼0.14) than the uncorrected model (∼0.04). The identifiability analysis showed that the proposed models had good quantification stability for [Formula: see text], [Formula: see text], and [Formula: see text] The [Formula: see text] estimated by the proposed model with simultaneous time-delay and dispersion corrections correlated inversely with age, as would be expected. Conclusion: Corrections to the input function are important for accurate lung kinetic analysis of HTR dynamic PET data. The modeling of both delay and dispersion can improve model fitting and significantly impact quantification of [Formula: see text], [Formula: see text], and [Formula: see text].