Measurement of liver blood flow using oxygen-15 labelled water and dynamic positron emission tomography: Limitations of model description

To date no satisfactory method has been available for the quantitative in vivo measurement of the complex hepatic blood flow. In this study two modelling approaches are proposed for the analysis of liver blood flow using positron emission tomography (PET). Five experiments were performed on three foxhounds. The anaesthetised dogs were each given an intravenous bolus injection of oxygen-15 labelled water, and their livers were then scanned using PET. Radioactivity in the blood from the aorta and portal vein was measured directly and simultaneously using closed external circuits. Time-activity curves were constructed from sequential PET data. Data analysis was performed by assuming that water behaves as a freely diffusible tracer and adapting the standard one-compartment blood flow model to describe the dual blood supply of the liver. Two particular modelling approaches were investigated: the dual-input model used both directly measured input functions (i.e. using the hepatic artery and the portal vein input, determined from the radioactivity detected in the aorta and portal vein respectively) whereas the single-input model used only the measured arterial curve and predicted the corresponding portal input function. Hepatic arterial flow, portal flow and blood volume were fitted from the PET data in several regions of the liver. The resulting estimates were then compared with reference blood flow measurements, obtained using a standard microsphere technique. The microspheres were injected in a separate experiment on the same dogs immediately prior to PET scanning. Whilst neither the single- nor the dual-input models accurately reproduced the arterial reference flow values, the flow values from the single-input model were closer to the microsphere flow values. The proposed single-input model would be a good approximation for liver blood flow measurements in man. The observed discrepancies between the PET and microsphere flow values may be due to the inherent temporal and spatial heterogeneity of liver blood flow. The results presented suggest that adaptation of the standard one-compartment blood flow model to describe the dual blood supply of the liver is limited and other flow tracers have to be considered for quantitative PET measurements in the liver.     

Liver kinetics of glucose analogs measured in pigs by PET: importance of dual-input blood sampling.

Metabolic processes studied by PET are quantified traditionally using compartmental models, which relate the time course of the tracer concentration in tissue to that in arterial blood. For liver studies, the use of arterial input may, however, cause systematic errors to the estimated kinetic parameters, because of ignorance of the dual blood supply from the hepatic artery and the portal vein to the liver. METHODS: Six pigs underwent PET after [15O]carbon monoxide inhalation, 3-O-[11C]methylglucose (MG) injection, and [18F]FDG injection. For the glucose scans, PET data were acquired for 90 min. Hepatic arterial and portal venous blood samples and flows were measured during the scan. The dual-input function was calculated as the flow-weighted input. RESULTS: For both MG and FDG, the compartmental analysis using arterial input led to systematic underestimation of the rate constants for rapid blood-tissue exchange. Furthermore, the arterial input led to absurdly low estimates for the extracellular volume compared with the independently measured hepatic blood volume of 0.25 +/- 0.01 mL/mL (milliliter blood per milliliter liver tissue). In contrast, the use of a dual-input function provided parameter estimates that were in agreement with liver physiology. Using the dual-input function, the clearances into the liver cells (K1 = 1.11 +/- 0.11 mL/min/mL for MG; K1 = 1.07 +/- 0.19 mL/min/mL for FDG) were comparable with the liver blood flow (F = 1.02 +/- 0.05 mL/min/mL). As required physiologically, the extracellular volumes estimated using the dual-input function were larger than the hepatic blood volume. The linear Gjedde-Patlak analysis produced parameter estimates that were unaffected by the choice of input function, because this analysis was confined to time scales for which the arterial-input and dual-input functions were very similar. CONCLUSION: Compartmental analysis of MG and FDG kinetics using dynamic PET data requires measurements of dual-input activity concentrations. Using the dual-input function, physiologically reasonable parameter estimates of K1, k2, and Vp were obtained, whereas the use of conventional arterial sampling underestimated these parameters compared with independent measurements of hepatic flow and hepatic blood volume. In contrast, the linear Gjedde-Patlak analysis, being less informative but more robust, gave similar parameter estimates (K, V) with both input functions.     

Estimation of the 18F-FDG input function in mice by use of dynamic small-animal PET and minimal blood sample data.

Derivation of the plasma time-activity curve in murine small-animal PET studies is a challenging task when tracers that are sequestered by the myocardium are used, because plasma time-activity curve estimation usually involves drawing a region of interest within the area of the reconstructed image that corresponds to the left ventricle (LV) of the heart. The small size of the LV relative to the resolution of the small-animal PET system, coupled with spillover effects from adjacent myocardial pixels, makes this method reliable only for the earliest frames of the scan. We sought to develop a method for plasma time-activity curve estimation based on a model of tracer kinetics in blood, muscle, and liver. METHODS: Sixteen C57BL/6 mice were injected with (18)F-FDG, and approximately 15 serial blood samples were taken from the femoral artery via a surgically inserted catheter during 60-min small-animal PET scans. Image data were reconstructed by use of filtered backprojection with CT-based attenuation correction. We constructed a 5-compartment model designed to predict the plasma time-activity curve of (18)F-FDG by use of data from a minimum of 2 blood samples and the dynamic small-animal PET scan. The plasma time-activity curve (TACp) was assumed to have 4 exponential components (TAC(P)=A(1)e(lambda(1)t)+A(2)e(lambda(2)t)+A(3)e(lambda(3)t)-(A(1)+A(2)+A(3))e(lambda(4)t)) based on the serial blood samples. Using Bayesian constraints, we fitted 2-compartment submodels of muscle and liver to small-animal PET data for these organs and simultaneously fitted the input (forcing) function to early small-animal PET LV data and 2 blood samples (approximately 10 min and approximately 1 h). RESULTS: The area under the estimated plasma time-activity curve had an overall Spearman correlation of 0.99 when compared with the area under the gold standard plasma time-activity curve calculated from multiple blood samples. Calculated organ uptake rates (Patlak K(i)) based on the predicted plasma time-activity curve had a correlation of approximately 0.99 for liver, muscle, myocardium, and brain when compared with those based on the gold standard plasma time-activity curve. The model was also able to accurately predict the plasma time-activity curve under experimental conditions that resulted in different rates of clearance of the tracer from blood. CONCLUSION: We have developed a robust method for accurately estimating the plasma time-activity curve of (18)F-FDG by use of dynamic small-animal PET data and 2 blood samples.     

Hepatic perfusion CT imaging analyzed by the dual-input one-compartment model

AIM: To improve liver-perfusion imaging by using the dual-input one-compartmental model. METHODS: Single-level dynamic computed tomography (dynamic CT) was taken at the height of the hepatic hilum after a rapid intravenous injection using 40 ml of iodinated contrast material. From the time-density curve of each pixel on CT, we calculated blood-flow rate constants of liver inflow and outflow. For inflow, two constants were calculated at arterial and portal veins. We postulated that blood flow between hepatic vessels and the hepatic parenchyma could be analyzed by using the calculated constants, and made equations for liver perfusion mapping. The perfusion images obtained by this method were compared with those made by the maximum slope method. RESULTS: We applied the method to a patient with hepatolithiasis. On dynamic CT, there was an abnormal enhancement pattern in the posterior segment of the liver. Perfusion CT images made by the dual-input one-compartment model demonstrated abnormal portal perfusion of the liver. In contrast, those made by the maximum-slope method did not represent the perfusion pattern well. CONCLUSION: The dual-input one-compartmental model makes it possible to obtain more detailed information on liver hemodynamics.     

Non-invasive estimation of hepatic glucose uptake from [18F]FDG PET images using tissue-derived input functions

Purpose

The liver is perfused through the portal vein and hepatic artery. Quantification of hepatic glucose uptake (HGU) using PET requires the use of an input function for both the hepatic artery and portal vein. The former can be generally obtained invasively, but blood withdrawal from the portal vein is not practical in humans. The aim of this study was to develop and validate a new technique to obtain quantitative HGU by estimating the input function from PET images.

Methods

Normal pigs (n?=?12) were studied with [¹⁸F]FDG PET, in which arterial and portal blood time-activity curves (TAC) were determined invasively to serve as reference measurements. The present technique consisted of two characteristics, i.e. using a model input function and simultaneously fitting multiple liver tissue TACs from images by minimizing the residual sum of square between the tissue TACs and fitted curves. The input function was obtained from the parameters determined from the fitting. The HGU values were computed by the estimated and measured input functions and compared between the methods.

Results

The estimated input functions were well reproduced. The HGU values, ranging from 0.005 to 0.02 ml/min per ml, were not significantly different between the two methods (r?=?0.95, p?<?0.001). A Bland-Altman plot demonstrated a small overestimation by the image-derived method with a bias of 0.00052 ml/min per g for HGU.

Conclusion

The results presented demonstrate that the input function can be estimated directly from the PET image, supporting the fully non-invasive assessment of liver glucose metabolism in human studies.     

Quantification of [(18)F]FDG uptake in the normal liver using dynamic PET: impact and modeling of the dual hepatic blood supply.

For quantification of hepatic [(18)F]FDG uptake, the dual blood supply to the liver must be considered. In contrast to the arterial input, however, the portal venous blood supply to the liver cannot be monitored directly by PET because of the inaccessibility of the portal vein on PET scans. In this study, we investigated whether the dual hepatic input can be predicted from the measurable arterial input. Moreover, we assessed the effect of different input models on the rate constants of the standard 3-compartment model describing regional uptake of FDG. METHODS: Dynamic FDG PET scanning was performed on 5 foxhounds. Activity concentrations in blood from the aorta and the portal vein were measured simultaneously using external circuits. After image reconstruction, time--activity courses were determined from the aorta and the liver. The venous input was approximated by convolving the arterial input with a notional system function describing the dispersion of the arterial input on its way through the gastrointestinal tract. On the basis of these data, 5 different hepatic input models, which pertain to a single-input as well as a dual-input scenario, were statistically compared with regard to the adequacy of the model fits to liver data and to differences in the estimated rate constants. RESULTS: Portal venous input to the liver could be approximated by convolving the arterial input function with a system function. From this function, a mean transit time of 25 s was computed for FDG to pass through the gastrointestinal tract. According to the statistical analysis, dual-input models were superior to their single-input counterparts. However, differences in the rate constants estimated for the 5 input models were in the same order as interindividual variations within the different model groups. For the dephosphorylation rate constant, a consistent value of 0.05 +/- 0.01 min(-1) was found. CONCLUSION: Dual-input models proved to be superior to single-input models with respect to the adequacy of FDG model fits to normal liver data. However, the hepatic blood supply may be approximated by the arterial input function as well, especially for the evaluation of liver lesions mainly fed by the hepatic artery.     

Tumor blood flow measured by PET dynamic imaging of first-pass 18F-FDG uptake: a comparison with 15O-labeled water-measured blood flow.

PET molecular imaging of 15O-labeled water is the gold standard for measuring blood flow in humans. However, this requires an on-site cyclotron to produce the short-lived 15O tracer, which is cost-prohibitive for most clinical PET centers. The purpose of this study was to determine if the early uptake of 18F-FDG could be used to measure regional blood flow in tumors in the absence of 15O-water. METHODS: PET scans were obtained in patients being evaluated for tumor perfusion and glucose metabolism in a phase I dose-escalating protocol for endostatin, a novel antiangiogenic agent. A 2-min perfusion scan was performed with a bolus injection of 2,220 MBq (60 mCi) of 15O-water, which was followed by a 370-MBq (10 mCi) dose of 18F-FDG. Four sequential scans of 18F-FDG uptake were acquired, consisting of an early 2-min uptake scan-or first-pass scan-and 3 sequential 15-min late 18F-FDG uptake scans. Regions of interest (ROIs) were drawn on 2 or more tumor sites and on back muscle, as a control ROI, for each patient. Arterial blood concentration was derived from the PET scans by drawing an ROI over a large artery in the field of view. Blood flow was computed with a simple 1-compartment blood flow model using the first 2 min of data after injection. RESULTS: Blood flow estimated from the early uptake of 18F-FDG was linearly correlated with 15O-measured blood flow, with an intercept of 0.01, a slope of 0.86, and an R2 regression coefficient of 0.74 (r = 0.86). The 18F-FDG tumor extraction fraction relative to 15O-water averaged 0.86. A preliminary case study of a patient with prostate cancer confirms the utility of the first-pass 18F-FDG blood flow analysis in tumor diagnosis. CONCLUSION: These results suggest that the first-pass uptake of 18F-FDG may provide an estimate of perfusion in a tumor within the limitations of incomplete extraction of 18F-FDG compared with 15O-water.     

A non-invasive isotope dilution technique for quantifying hepatic blood flow using radiolabelled red blood cells

Clinically significant changes in hepatic haemodynamics accompany the development of portal hypertension, hepatocellular carcinoma, liver metastases and liver cirrhoses, and after major liver resection. Hepatic blood flow parameters, such as hepatic arterial flow (HAF), hepatic portal flow (HPF), total hepatic blood flow (THBF) and hepatic perfusion index (HPI), are useful adjuncts to the diagnosis of liver pathology, the evaluation of disease progress and prognostication. Here, we describe a non-invasive method that combines the measurement of these parameters in a single study in real time. Red blood cells from eight pigs were labelled with 99Tc(m) using an in-vitro method and re-injected into the pigs. Data acquisition over the heart, lungs, liver and kidneys was started immediately and a blood sample was obtained 15 min post-injection. Hepatic arterial flow was determined from the ratio of the maximum gradients between the integrated time-activity curve of the left ventricle and the first-pass time-activity curve of the liver before the peak of the kidneys time-activity curve. The hepatic perfusion index was determined by comparing the slope of the liver time-activity curve before and after the kidney peak. Hepatic portal flow was determined from the hepatic arterial flow and the hepatic perfusion index, and total hepatic blood flow was determined as the sum of arterial and portal flow. The results were compared against those obtained from a clearance method using 99Tc(m)-DISIDA. The average hepatic perfusion index was 0.38, and the average hepatic arterial flow and hepatic portal flow were 168.3 +/- 52.9 and 274.6 +/- 60.1 ml x min(-1) respectively. The average total hepatic blood flow was 442.8 +/- 53.5 ml x min(-1), while the total hepatic flow determined by 99Tc(m)-DISIDA clearance was 419.7 +/- 62.6 ml x min(-1). No significant difference in total hepatic blood flow was found between the two methods. The results of this study show that it is possible to obtain all hepatic haemodynamics data in a single study using a non-invasive method.     

多层面螺旋CT对肝移植术后肝动脉狭窄肝灌注的研究

目的　利用动态单层CT扫描对原位肝移植术后肝动脉狭窄肝灌注与未行肝移植、无肝脏病变者进行比较。资料与方法　对 30例肝移植术后肝动脉狭窄患者选取肝门 (包括肝、门静脉、主动脉和脾 )层面行动态单层CT扫描。高压注射器经肘静脉注射非离子型对比剂欧乃派克 4 0ml,流率 3ml/s,注射对比剂时即进行扫描 ,每间隔1s扫 1层 ,共扫描 35层。通过每一层面选定的ROI作CT值测量 ,绘制出时间 密度曲线 ,从而计算出相应灌注值并与未行肝移植、无肝脏病变者进行对照。结果　肝移植术后肝动脉狭窄 <5 0 %组 ,肝动脉灌注 (t=0 .5 ,P >0 .0 5 )、门静脉灌注 (t=1 ,P >0 .0 5 )与对照组间无显著差异 ;肝动脉狭窄≥ 5 0 % ,肝动脉灌注与对照组存在差异 (t =2 .1 4 ,P <0 .0 5 ) ,低于对照组 ,门静脉灌注与对照组有差异 (t=2 .6 3,P <0 .0 5 ) ,高于对照组。结论　肝移植术后肝动脉狭窄≥ 5 0 % ,肝动脉灌注降低而门静脉灌注升高。动态单层CT扫描对于评价肝移植术后肝脏灌注是有帮助的     

Dynamic CT scanning of the normal canine liver: interpretation of time density curves resulting from an intravenous bolus injection of contrast material

Seven adult male mongrel dogs were monitored by electromagnetic flow probes and string occluders around the hepatic artery and portal vein. Then, time density curves of the liver, aorta and portal vein were recorded using dynamic CT scanning following the bolus injection of contrast material into a peripheral vein (n = 7) and a mesenteric vein branch (n = 5). Information on total hepatic blood flow could not be obtained from the mesenteric vein injection. The hepatic time density curve could, however, be broken into its two components, hepatic arterial and portal venous flow contribution, by selective ligation of the hepatic artery or portal vein. It could be demonstrated that the arterial component of liver enhancement reached its peak at the end of the aortic wash-out of contrast material. Thus, the hepatic time-density curve could be broken in its two components by superimposing the aortic time density curve onto the hepatic curve. An attempt was made to estimate relative portal venous blood flow by using the slopes or the peaks of both components of the hepatic curve. Using the slopes of the hepatic curve resulted in a consistent underestimation of portal venous blood flow, whereas the peaks gave an estimate of portal venous flow with an accuracy within +/- 8%.     

Minimally invasive method of determining blood input function from PET images in rodents.

For cardiovascular research on rodents, small-animal PET has limitations because of the inherent spatial resolution of the system and because of cardiac motion. A factor analysis (FA) technique for extracting the blood input function and myocardial time-activity curve from dynamic small-animal PET images of the rodent heart has been implemented to overcome these limitations. METHODS: Six Sprague-Dawley rats and 6 BALB/c mice underwent dynamic imaging with 18F-FDG (n = 6) and 1-11C-acetate (n = 6). From the dynamic images, blood input functions and myocardial time-activity curves were extracted by the FA method. The accuracy of input functions derived by the FA method was compared with that of input functions determined from serial blood samples, and the correlation coefficients were calculated. RESULTS: Factor images (right ventricle, left ventricle, and myocardium) were successfully extracted for both 18F-FDG and 1-11C-acetate in rats. The correlation coefficients for the input functions were 0.973 for 18F-FDG and 0.965 for 1-11C-acetate. In mice, the correlation coefficients for the input functions were 0.930 for 18F-FDG and 0.972 for 1-11C-acetate. CONCLUSION: The FA method enables minimally invasive extraction of accurate input functions and myocardial time-activity curves from dynamic microPET images of rodents without the need to draw regions of interest and without the possible complications of surgery and repeated blood sampling.     

Assessment of hepatic perfusion parameters with dynamic MRI.

Quantification of hepatic perfusion parameters greatly contributes to the assessment of liver function. The purpose of this study was to describe and validate the use of dynamic MRI for the noninvasive assessment of hepatic perfusion parameters. The signal from a fast T(1)-weighted spoiled gradient-echo sequence preceded by a nonslice-selective 90 degrees pulse and a spoiler gradient was calibrated in vitro with tubes filled with various gadolinium concentrations. Dynamic images of the liver were obtained after intravenous bolus administration of 0.05 mmol/kg of Gd-DOTA in rabbits with normal liver function. Hepatic, aortic, and portal venous signal intensities were converted to Gd-DOTA concentrations according to the in vitro calibration curve and fitted with a dual-input one-compartmental model. With MRI, hepatic blood flow was 100 +/- 35 mL min(-1) 100 mL(-1), the arterial fraction 24 +/- 11%, the distribution volume 13.0 +/- 3.7%, and the mean transit time 8.9 +/- 4.1 sec. A linear relationship was observed between perfusion values obtained with MRI and with radiolabeled microspheres (r = 0.93 for hepatic blood flow [P < 0.001], r = 0.79 for arterial blood flow [P = 0.01], and r = 0.91 for portal blood flow [P < 0.001]). Our results indicate that hepatic perfusion parameters can be assessed with dynamic MRI and compartmental modeling.     

The effect of methodology and tracer identity on a non-invasive index of liver blood flow

There are a number of clinical conditions in which quantification of the relative flow in the arterial and portal vessels supplying the liver may be of diagnostic use. The hepatic perfusion index has been proposed as a non-invasive indicator of relative blood flows. The technique involves analysis of first-pass time-activity curves over the liver and kidney with the calculations of an index which is derived from the slopes of the hepatic curve before and after the renal peak. In previously published studies, the methodology adopted has been variable, both in the analysis and in tracer identity. This study examines the effect of both physical and physiological variables on the index. The results indicate that in addition to relative arterial and portal flows, the index is dependent on bolus quality, the length of time over which the slopes are averaged, transit times through the liver and splenic and mesenteric circulations, and the degree of tracer extraction. Furthermore, the data suggest that values in the currently considered abnormal range may be poor indicators of relative arterial and portal venous flows.     

Hepatic metastases: in vivo assessment of perfusion parameters at dynamic contrast-enhanced MR imaging with dual-input two-compartment tracer kinetics model

This study was institutional review board approved, with waived patient consent for retrospective analysis of the data. The hepatic perfusion at dynamic contrast material-enhanced magnetic resonance (MR) imaging was commonly described and assessed by using a dual-input one-compartment tracer kinetics model. Although the tracer kinetics in normal liver parenchyma can be described by using a single compartment, functional changes in the tumor microenvironment can result in distinctly different tracer behavior that entails a second tissue compartment. A dual-input two-compartment model is proposed to describe the tracer behavior in hepatic metastases. The authors applied this model to the dynamic MR imaging data obtained in three patients. Perfusion parameter maps and region-of-interest analysis revealed that tracer behavior in hepatic metastases-in contrast to that in surrounding normal liver tissue, which effectively involves one compartment-can be described by using two compartments.     

基于人工免疫网络的小动物PET分子影像动力学参数估计方法

目的基于人工免疫网络提出无需设定初值的示踪剂动力学模型参数估计算法,以提高PET分子影像动力学模型分析方法的可靠性。方法对18F—FDG小鼠PET显像实验中有关数据,用ROI技术获取肝和左心室示踪剂的时间一放射性曲线（TAC）,同时经小鼠尾静脉多点采血获取尾静脉血TAC。对动物实验数据进行示踪剂药代动力学建模,设计人工免疫网络算法估计模型参数,并计算小鼠肝葡萄糖代谢率参数Ki。结果获得肝、左心室和尾静脉血TAC。对小动物实验数据建模,应用基于人工免疫网络的药代动力学参数优化方法（PKAIN）求解模型参数,实现无需设定初始值的模型参数估计,并计算3只小鼠K值,平均值分别为0．0024,0．0417和0．0047。PKAIN算法求出对输出模型参数估计的最大加权残差平方和的平均值小于0．0745,标准差最大为0．0084,表明能够获得准确稳定的模型参数。结论人工免疫网络智能计算方法可提高PET分子影像动力学建模方法的可靠性、实用性提供了新型的智能信息处理技术。     

肝脏灌注成像的CT扫描方法及应用价值

目的:探讨单层CT动态增强扫描测定肝硬化肝脏血流量的扫描方法及其应用价值。方法:15例经临床、实验室及B超检查诊断为肝硬化的患者,其中ChildB级患者10例,ChildC级患者5例。对照组为13例无肝脏疾病的患者。所有患者均选取同时含有肝脏、脾脏、主动脉和门静脉的层面进行单层CT动态增强扫描,绘制感兴趣区时间密度曲线,计算各血流灌注参数。结果:单层CT动态增强扫描测量肝组织的肝动脉灌注量(HAP)、门静脉灌注量(PVP)、总肝血流量(THBF)和肝动脉灌注指数(HPI)。正常组的HAP、PVP、THBF和HPI分别为(0.28±0.10)ml/min·ml、(1.18±0.40)ml/min·ml、(1.46±0.44)ml/min·ml和(19.73±5.81)%;肝硬化组的HAP、PVP、THBF和HPI分别为(0.23±0.11)ml/min·ml、(0.61±0.25)ml/min·ml、(0.84±0.32)ml/min·ml和(27.16±12.75)%。结论:肝脏单层CT灌注成像,可定量测定各项肝脏血流灌注参数,对肝硬化患者的量化诊断有一定的参考价值。     

Tracer input for kinetic modelling of liver physiology determined without sampling portal venous blood in pigs

Purpose  

Quantification of hepatic tracer kinetics by PET requires measurement of tracer input from the hepatic artery (HA) and portal vein (PV). We wished to develop a method for estimating dual tracer input without the necessity to sample PV blood.     

An efficient method for calculating kinetic parameters in a dual-input single-compartment model

Quantitative measurement of hepatic perfusion has the potential to provide important information in the assessment and management of various liver diseases. The utility of hepatic perfusion characterization relies on the resolution of each component of its dual blood supply, i.e. the hepatic artery and portal vein. In this study, a linear equation was derived by integrating the differential equation describing the kinetic behaviour of contrast agent (CA) in a dual-input single-compartment model, from which the kinetic parameters can be easily obtained using the linear least-squares method. The usefulness of this method was investigated using computer simulations, in comparison with the non-linear least-squares (NLSQ) method. This method calculated the kinetic parameters faster than the NLSQ method by a factor of approximately 10, with almost the same accuracy as the NLSQ method. This method will be useful for analysing the kinetic behaviour of CA in the unique liver environment, especially by generating the functional images of kinetic parameters.     

Comparison of methods to quantitate 18F-FDG uptake with PET during experimental acute lung injury.

PET with 18F-FDG may be useful for quantifying neutrophilic activation. We previously demonstrated that pulmonary neutrophil sequestration could be detected during acute lung injury (ALI), even without migration into the alveolar compartment. Using the influx constant Ki as the method to quantify lung 18F-FDG uptake, we also showed that Ki correlated positively with in vitro assays of 3H-deoxyglucose (3H-DG) uptake in cells harvested via bronchoalveolar lavage. In the present study, we have reanalyzed data from that study to determine if simpler nonkinetic methods of quantifying the pulmonary uptake of 18F-FDG could be as powerful as calculating Ki. METHODS: 18F-FDG uptake was quantified as Ki, calculated by 3-compartmental model analysis (used as the gold standard) and Patlak graphical analysis, with and without normalization for initial volume of tracer distribution; the standardized uptake value; and the tissue-to-plasma activity ratio (TPR). RESULTS: Values for Ki, determined either from a 3-compartmental model analysis of the time-activity data or by Patlak graphical analysis, were highly correlated (R2 = 0.97). The correlation was worse if these variables were normalized for the initial volume of tracer distribution. TPR was highly correlated with Ki determined by the compartmental model (R2 = 0.96) and with in vitro measurements of 3H-DG uptake (R2 = 0.63). CONCLUSION: The TPR is a simple and equally effective alternative to dynamic imaging in determining net 18F-FDG uptake during ALI. Normalization of the kinetic data for differences in the initial volume of tracer distribution does not contribute significantly to signal interpretation during ALI.     

Non-invasive estimation of hepatic blood perfusion from H2 15O PET images using tissue-derived arterial and portal input functions

Purpose  The liver is perfused through the portal vein and the hepatic artery. When its perfusion is assessed using positron emission tomography (PET) and ¹⁵O-labeled water (H₂ ¹⁵O), calculations require a dual blood input function (DIF), i.e., arterial and portal blood activity curves. The former can be generally obtained invasively, but blood withdrawal from the portal vein is not feasible in humans. The aim of the present study was to develop a new technique to estimate quantitative liver perfusion from H₂ ¹⁵O PET images with a completely non-invasive approach. Methods  We studied normal pigs (n = 14) in which arterial and portal blood tracer concentrations and Doppler ultrasonography flow rates were determined invasively to serve as reference measurements. Our technique consisted of using model DIF to create tissue model function and the latter method to simultaneously fit multiple liver time–activity curves from images. The parameters obtained reproduced the DIF. Simulation studies were performed to examine the magnitude of potential biases in the flow values and to optimize the extraction of multiple tissue curves from the image. Results  The simulation showed that the error associated with assumed parameters was <10%, and the optimal number of tissue curves was between 10 and 20. The estimated DIFs were well reproduced against the measured ones. In addition, the calculated liver perfusion values were not different between the methods and showed a tight correlation (r = 0.90). Conclusion  In conclusion, our results demonstrate that DIF can be estimated directly from tissue curves obtained through H₂ ¹⁵O PET imaging. This suggests the possibility to enable completely non-invasive technique to assess liver perfusion in patho-physiological studies.