Quantification Of Physiological Parameters Research Articles

Optimization-derived blood input function using a kernel method and its evaluation with total-body PET for brain parametric imaging

Dynamic PET allows quantification of physiological parameters through tracer kinetic modeling. For dynamic imaging of brain or head and neck cancer on conventional PET scanners with a short axial field of view, the image-derived input function (ID-IF) from intracranial blood vessels such as the carotid artery (CA) suffers from severe partial volume effects. Alternatively, optimization-derived input function (OD-IF) by the simultaneous estimation (SIME) method does not rely on an ID-IF but derives the input function directly from the data. However, the optimization problem is often highly ill-posed. We proposed a new method that combines the ideas of OD-IF and ID-IF together through a kernel framework. While evaluation of such a method is challenging in human subjects, we used the uEXPLORER total-body PET system that covers major blood pools to provide a reference for validation. MethodsThe conventional SIME approach estimates an input function using a joint estimation together with kinetic parameters by fitting time activity curves from multiple regions of interests (ROIs). The input function is commonly parameterized with a highly nonlinear model which is difficult to estimate. The proposed kernel SIME method exploits the CA ID-IF as a priori information via a kernel representation to stabilize the SIME approach. The unknown parameters are linear and thus easier to estimate. The proposed method was evaluated using 18F-fluorodeoxyglucose studies with both computer simulations and 20 human-subject scans acquired on the uEXPLORER scanner. The effect of the number of ROIs on kernel SIME was also explored. ResultsThe estimated OD-IF by kernel SIME showed a good match with the reference input function and provided more accurate estimation of kinetic parameters for both simulation and human-subject data. The kernel SIME led to the highest correlation coefficient (R = 0.97) and the lowest mean absolute error (MAE = 10.5 %) compared to using the CA ID-IF (R = 0.86, MAE = 108.2 %) and conventional SIME (R = 0.57, MAE = 78.7 %) in the human-subject evaluation. Adding more ROIs improved the overall performance of the kernel SIME method. ConclusionThe proposed kernel SIME method shows promise to provide an accurate estimation of the blood input function and kinetic parameters for brain PET parametric imaging.

Unfolded Protein Response in Arabidopsis.

The unfolded protein response (UPR) is a highly regulated signaling pathway that is largely conserved across eukaryotes. It is essential for cell homeostasis under environmental and physiological conditions that perturb the protein folding in the endoplasmic reticulum (ER). Arabidopsis is one of the outstanding multicellular model systems in which to investigate the UPR. Here, we described a protocol to induce the UPR in plants, specifically Arabidopsis, and to estimate their ability to cope with ER stress through the quantification of physiological parameters.

Evaluation of Potential Effects of Increased Outdoor Temperatures Due to Global Warming on Cerebral Blood Flow Rate and Respiratory Function in Chronic Obstructive Disease and Anemia.

Global warming due to increased outdoor carbon dioxide (CO2) levels may cause several health problems such as headaches, cognitive impairment, or kidney dysfunction. It is predicted that further increases in CO2 levels will increase the morbidity and mortality of patients affected by a variety of diseases. For instance, patients with Chronic Obstructive Pulmonary Disease (COPD) may suffer cognitive impairments or intracranial bleeding due to an increased cerebral blood flow rate. Predicting the harmful effects of global warming on human health will help to take measures for potential problems. Therefore, the quantification of physiological parameters is an essential step to investigate the effects of global warming on human health. In this study, the effects of increased outdoor temperatures due to climate change on cerebral blood flow rate and respiratory function in healthy subjects and COPD patients with anemia and respiratory acidosis are evaluated utilizing numerical simulations. The numerical model simulates cardiac function and blood circulation in systemic, pulmonary and cerebral circulations, cerebral autoregulatory functions, respiratory function, alveolar gas exchange, oxygen (O2) and CO2 contents, and hemoglobin levels in the blood. The simulation results show that although the cardiovascular function is not significantly altered, the respiratory function and cerebral blood flow rates are altered remarkably.

The ultra high sensitivity blood counter: a compact, MRI-compatible, radioactivity counter for pharmacokinetic studies in μl volumes

Quantification of physiological parameters in preclinical pharmacokinetic studies based on nuclear imaging requires the monitoring of arterial radioactivity over time, known as the arterial input function (AIF). Continuous derivation of the AIF in rodent models is very challenging because of the limited blood volume available for sampling. To address this challenge, an Ultra High Sensitivity Blood Counter (UHS-BC) was developed. The device detects beta particles in real-time using silicon photodiodes, custom low-noise electronics, and 3D-printed plastic cartridges to hold standard catheters. Two prototypes were built and characterized in two facilities. Sensitivities up to 39% for 18F and 58% for 11C-based positron emission tomography (PET) tracers were demonstrated. 99mTc and 125I based Single Photon Emission Computed Tomography (SPECT) tracers were detected with greater than 3% and 10% sensitivity, respectively, opening new applications in nuclear imaging and fundamental biology research. Measured energy spectra show all relevant peaks down to a minimum detectable energy of 20 keV. The UHS-BC was shown to be highly reliable, robust towards parasitic background radiation and electromagnetic interference in the PET or MRI environment. The UHS-BC provides reproducible results under various experimental conditions and was demonstrated to be stable over days of continuous operation. Animal experiments showed that the UHS-BC performs accurate AIF measurements using low detection volumes suitable for small animal models in PET, SPECT and PET/MRI investigations. This tool will help to reduce the time and number of animals required for pharmacokinetic studies, thus increasing the throughput of new drug development.

Effect of daily exposure to Pb-contaminated water on Salvinia biloba physiology and phytoremediation performance

Lead (Pb) removal from water column was evaluated in batch experiments using naturally occurring Salvinia biloba Raddi (S. biloba) specimens collected from Middle Paraná River and exposed every 24 h to a fresh discharge of water contaminated with 2.65 ± 0.07, 12.62 ± 0.02 or 30.57 ± 0.01 mg L−1 Pb, during 10 consecutive days. S. biloba demonstrated a great ability for metal concentration-dependent Pb removal under these stressful conditions. Additionally, Pb toxicity in plants was assessed by the quantification of physiological parameters in root-like modified fronds (named “roots”), and its aerial leaf-like fronds (named “leaves”) of submerged S. biloba. Photosynthetic (carotenoids, chlorophyll a, b, and total) and antioxidant pigments (anthocyanins and flavonoids), soluble carbohydrate content, and membrane stability index of both roots and leaves were affected as the metal concentration increased. In general, root deterioration was more pronounced than that in leaves, suggesting a greater implication of the former organs in Pb removal by S. biloba. All of these deleterious effects were well correlated with qualitative changes observed at plant phenotype during the assay. In conclusion, S. biloba may be considered as a water fern useful in phytoremediation strategies towards management of residual water bodies contaminated with Pb. In addition, these macrophytes could also be valuable for water biomonitoring contributing to improve risk assessments related to metal presence in wastewaters.

Unfolded Protein Response in Arabidopsis.

The unfolded protein response (UPR) is a highly regulated signaling pathway that is largely conserved across eukaryotes. It is essential for cell homeostasis under environmental and physiological conditions that perturb the protein folding in the endoplasmic reticulum (ER). Arabidopsis is one of the outstanding multicellular model systems in which to investigate the UPR. Here, we described a protocol to induce the UPR in plants, specifically arabidopsis, and to estimate their ability to cope with ER stress through the quantification of physiological parameters.

Evaluation of acute skin toxicity in breast radiotherapy with a new quantitative approach

Background and purposeCurrent criteria to evaluate acute radiodermatitis are highly subjective so quantification of physiological parameters is needed. We describe a non-invasive method of assessing skin microcirculation in breast cancer patients treated with hypofractionated radiotherapy and correlate them with the CTCAE scale. MethodsProspective study of 63 patients where blood flow was measured with real-time laser Doppler flowmetry (LDF) at baseline, weekly, and 3-months post-radiotherapy. Skin toxicity was assessed with the microcirculation index (MCI), a novel index based on blood flow parameters obtained via LDF. ResultsMCI was positively correlated (R=0.647; p<0.001) with the dose. Changes in MCI from baseline to the end of radiotherapy and at 3-months post-radiotherapy were significant (p<0.001). All CTCAE groups experienced a significant increase in MCI values from baseline to end of radiotherapy (p<0.001 for CTCAE grades 0 and 1; and p=0.028 for the grade 2 group). Significant differences in MCI values were observed among CTCAE groups at the end of radiotherapy (p=0.016). ConclusionsLDF is an accurate and objective measure of changes in blood flow. The comparison with the CTCAE shows the limitations of this subjective way of classifying patients. LDF is the first step for future studies of radiodermatitis treatments and prevention.

Comparison of non-linearity correction methods for quantitative myocardial perfusion MRI

Background Quantification of physiological parameters, including myocardial blood flow (MBF), by perfusion MRI relies on analysis of data that describes temporal variation of relative contrast agent concentration following bolus administration. At doses required for sufficient SNR, signal enhancement cannot be used directly as the relationship between signal intensity (SI) and the resulting concentrations in blood and myocardium is non-linear. Proposed solutions to this include separation of the AIF and myocardial data acquisition, or model based non-linearity correction.

Global-two-stage filtering of clinical PET parametric maps: Application to [11C]-(R)-PK11195

IntroductionIn Positron Emission Tomography (PET) quantification of physiological parameters at the voxel level may result in unreliable estimates due to the high noise of voxel time activity curves. Global-Two-Stage (GTS), an estimation technique belonging to the group of “population approaches”, can be used to tackle this problem. GTS was previously tested on simulated PET data and yielded substantial improvements when compared to standard estimation approaches such as Weighted NonLinear Least Squares (WNLLS) and Basis Function Method (BFM). In this work GTS performance is assessed in a clinical context using the neuroinflammation marker [11C]-(R)-PK11195 applied to a cohort of Huntington's disease (HD) patients with and without symptoms. Materials and methodsParametric maps of binding potential (BPND) of 12 normal controls (NC), 9 symptomatic and 9 presymptomatic HD patients were generated by applying a modified reference tissue model that accounts for tracer vascular activity in both reference and target tissues (SRTMV). GTS was then applied to SRTMV maps and its performance compared with that of SRTMV. Three smoothed versions of SRTMV, obtained by filtering the original SRTMV maps with Gaussian filters of 3mm, 5mm and 7mm Full Width Half Maximum (FWHM), were also included in the comparison. Since striatal degeneration is the hallmark of HD, sensitivity was assessed for all methods by computing the mean of z-scores in caudate, putamen and globus pallidus in the voxel-by-voxel statistical comparison of BPND between HD and NC. ResultsApplication of GTS to parametric maps brought a substantial qualitative improvement to SRTMV maps to the extent that anatomical structures often became visible. In addition, most parameter estimates that were outside the physiological range with SRTMV were corrected by GTS. GTS yielded a 2.3-fold increase in sensitivity with respect to SRTMV for the symptomatic cohort (mean of striatal z-scores of 0.76 for SRTMV and 1.79 for GTS) and an even more substantial increase for the presymptomatic cohort (mean of striatal z-scores of 0.34 for SRTMV and 0.96 for GTS). The sensitivity of GTS was similar to the one obtained with a filter of 7mm FWHM applied to the initial SRTMV maps but GTS images were not characterized by the notable loss of resolution typical of smoothed maps. GTS, additionally, does not require to change/define settings according to the tracer and level of noise, whereas the choice of the FWHM value of the Gaussian filter normally employed in the smoothing procedure is typically arbitrary. ConclusionsGTS is a powerful and robust tool for improving the quality of parametric maps in PET. The method is particularly appealing in that it can be applied to any tracer and estimation method, provided that initial estimates of the parameter vector and of its covariance are available. Although the benefits of GTS are far from being exhaustively assessed, the significant improvements obtained both on real and simulated data suggest that it could become an important tool for dynamic PET in the future.