Blood Input Function Research Articles

Differentiation of Glioblastomas from Metastatic Brain Tumors by Tryptophan Uptake and Kinetic Analysis: A Positron Emission Tomographic Study with Magnetic Resonance Imaging Comparison

Differentiating high-grade gliomas from solitary brain metastases is often difficult by conventional magnetic resonance imaging (MRI); molecular imaging may facilitate such discrimination. We tested the accuracy of α[11C]methyl-l-tryptophan (AMT)-positron emission tomography (PET) to differentiate newly diagnosed glioblastomas from brain metastases. AMT-PET was performed in 36 adults with suspected brain malignancy. Tumoral AMT accumulation was measured by standardized uptake values (SUVs). Tracer kinetic analysis was also performed to separate tumoral net tryptophan transport (by AMT volume of distribution [VD]) from unidirectional uptake rates using dynamic PET and blood input function. Differentiating the accuracy of these PET variables was evaluated and compared to conventional MRI. For glioblastoma/metastasis differentiation, tumoral AMT SUV showed the highest accuracy (74%) and the tumor/cortex VD ratio had the highest positive predictive value (82%). The combined accuracy of MRI (size of contrast-enhancing lesion) and AMT-PET reached up to 93%. For ring-enhancing lesions, tumor/cortex SUV ratios were higher in glioblastomas than in metastatic tumors and could differentiate these two tumor types with > 90% accuracy. These results demonstrate that evaluation of tryptophan accumulation by PET can enhance pretreatment differentiation of glioblastomas and metastatic brain tumors. This approach may be particularly useful in patients with a newly diagnosed solitary ring-enhancing mass.

Quantitative PET Imaging Detects Early Metabolic Remodeling in a Mouse Model of Pressure-Overload Left Ventricular Hypertrophy In Vivo

We proposed that metabolic remodeling in the form of increased uptake of the myocardial glucose analog (18)F-FDG precedes and triggers the onset of severe contractile dysfunction in pressure-overload left ventricular hypertrophy in vivo. To test this hypothesis, we used a mouse model of transverse aortic constriction (TAC) together with PET and assessed serial changes in cardiac metabolism and function over 7 d. Scans of 16 C57BL/6 male mice were obtained using a small-animal PET device under sevoflurane anesthesia. A 10-min transmission scan was followed by a 60-min dynamic (18)F-FDG PET scan with cardiac and respiratory gating. Blood glucose levels were measured before and after the emission scan. TAC and sham surgeries were performed after baseline imaging. Osmotic mini pumps containing either propranolol (5 mg/kg/d) or vehicle alone were implanted subcutaneously at the end of surgery. Subsequent scans were taken at days 1 and 7 after surgery. A compartment model, in which the blood input function with spillover and partial-volume corrections and the metabolic rate constants in a 3-compartment model are simultaneously estimated, was used to determine the net myocardial (18)F-FDG influx constant, Ki. The rate of myocardial glucose utilization, rMGU, was also computed. Estimations of the ejection fractions were based on the high-resolution gated PET images. Mice undergoing TAC surgery exhibited an increase in the Ki (580%) and glucose utilization the day after surgery, indicating early adaptive response. On day 7, the ejection fraction had decreased by 24%, indicating a maladaptive response. Average Ki increases were not linearly associated with increases in rMGU. Ki exceeded rMGU by 29% in the TAC mice. TAC mice treated with propranolol attenuated the rate of (18)F-FDG uptake, diminished mismatch between Ki and rMGU (9%), and rescued cardiac function. Metabolic maladaptation precedes the onset of severe contractile dysfunction. Both are prevented by treatment with propranolol. The early detection of metabolic remodeling may offer a metabolic target for modulation of hypertrophy.

Synthesis and Evaluation of 11C-LY2795050 as a κ-Opioid Receptor Antagonist Radiotracer for PET Imaging

Kappa-opioid receptors (KOR) are believed to be involved in the pathophysiology of depression, anxiety disorders, drug abuse, and alcoholism. To date, only 1 tracer, the KOR agonist (11)C-GR103545, has been reported to be able to image KOR in primates. The goal of the present study was to synthesize the selective KOR antagonist (11)C-LY2795050 and evaluate its potential as a PET tracer to image KOR in vivo. The in vitro binding affinity of LY2795050 was measured in radioligand competition binding assays. Ex vivo experiments were conducted using microdosing of the unlabeled ligand in Sprague-Dawley rats and in wild-type and KOR knockout mice, to assess the ligand's potential as a tracer candidate. Imaging experiments with (11)C-LY2795050 in monkeys were performed on the Focus-220 scanner with arterial blood input function measurement. Binding parameters were determined with kinetic modeling analysis. LY2795050 displays full antagonist activity and high binding affinity and selectivity for KOR. Microdosing studies in rodents and ex vivo analysis of tissue concentrations with liquid chromatography-tandem mass spectrometry identified LY2795050 as an appropriate tracer candidate able to provide specific binding signals in vivo. (11)C-LY2795050 was prepared in an average yield of 12% and greater than 99% radiochemical purity. In rhesus monkeys, (11)C-LY2795050 displayed a moderate rate of peripheral metabolism, with approximately 40% of parent compound remaining at 30 min after injection. In the brain, (11)C-LY2795050 displayed fast uptake kinetics (regional activity peak times of <20 min) and an uptake pattern consistent with the distribution of KOR in primates. Pretreatment with naloxone (1 mg/kg, intravenously) resulted in a uniform distribution of radioactivity. Further, specific binding of (11)C-LY2795050 was reduced by the selective KOR antagonist LY2456302 in a dose-dependent manner. (11)C-LY2795050 displayed favorable pharmacokinetic properties and binding profiles in vivo and therefore is a suitable ligand for imaging the KOR in primates. This newly developed KOR antagonist tracer has since been advanced to PET imaging of KOR in humans and constitutes the first successful KOR antagonist radiotracer.

Non-Negative Matrix Factorization Based Input Function Extraction for Mouse Imaging in Small Animal PET ? Comparison with Arterial Blood Sampling and Factor Analysis

Objectives: Retrieving the accurate time-tracer activity concentration curve of the blood (arterial input function) is mandatory for performing bio kinetic model analysis of dynamic PET data. Especially in small rodents, gathering the input function remains an active area of research as no generally applicable solution was found so far. While surgically catheterizing blood vessels of rodents is possible, it is labour intensive and time resolution of blood sampling is restricted due to the limited amount of overall blood and the procedure of blood withdrawal itself. Obtaining the input function from the PET images themselves seems thus to be favourable, but suffers from several factors, one of them being spill-in of adjacent tissues. Particularly in mice and for [18F]FDG, the spill-in complicates using the time-activity curve (TAC) from a region of interest (ROI) over the left ventricle (LV) because the signal of the ROI contains contributions from both, myocardial uptake as well as arterial blood activity. We propose non-negative matrix factorization (NMF) as an image based algorithm for separating myocardial tracer concentration from the blood input function. The aim of this study was to evaluate the potential of NMF as an image based algorithm for retrieving the input function by comparison with blood sampling and Factor Analysis (FA). Method: The femoral arteries of eight mice were surgically catheterized. With the injection of [18F]FDG, a 60 minute PET scan was started during which arterial blood samples were manually drawn from the catheter. For analysis, NMF and FA were performed in a ROI placed over the LV. The NMF algorithm shares similarities with principal component analysis and FA, the advantage over the later two being its non-negativity constraint. For normalization of the NMF extracted curve, the peak value of tracer activity in an early image of the LV and a late blood sample was used. The normalized NMF curve was visually compared to the TAC retrieved from the blood samples and to the FA retrieved TAC. For a quantitative comparison of performance, Pearson correlation and square-root of sum of squares (RSS) between NMF/FA and blood sampling curves was calculated. Results: TAC based on NMF, FA and arterial blood samples were obtained and compared in all 8 mice. The NMF derived curves described the blood sampling based curves visually significantly better than FA. Pearson correlation between NMF and blood sampling curves ranged from 0.21 to 0.92 with an average of 0.69. Pearson correlation for FA ranged from 0.46 to 0.81 with an average of 0.65. Mean RSS was 2.70E + 006 for NMF and 3.40E + 006 for FA. Conclusion: In the examined parameters, visual accordance, Pearson correlation and RSS, NMF performs superior to FA and seems to be a promising method for the extraction of the input function from PET images of small rodents without the need for arterial blood sampling.

Multislice cardiac arterial spin labeling using improved myocardial perfusion quantification with simultaneously measured blood pool input function

Myocardial blood flow (MBF) is an important indicator of cardiac tissue health, which can be measured using arterial spin labeling. This study aimed to develop a new method of MBF quantification with blood pool magnetization measurement ("bpMBF quantification") that allows multislice cardiac arterial spin labeling. A multislice segmented ECG-gated Look-Locker T1 mapping sequence was validated. Quantification of multislice arterial spin labeling is not straightforward due to the large volume of blood inverted following slice-selective inversion. For bpMBF quantification, a direct measurement of the left-ventricle blood pool magnetization was used to approximate the blood input function into the Bloch equations. Simulations and in vivo measurements in the mouse heart were performed to evaluate the bpMBF method. Measurements indicated that blood pool magnetization requires ∼3 s to return to equilibrium following slice-selective inversion. Simulation and in vivo results show that bpMBF quantification is robust to variations in slice-selective thickness and therefore applicable to multislice acquisition, whereas traditional methods are likely to underestimate multislice perfusion. In vivo, single and multislice perfusion values matched well when quantified using bpMBF. The first multislice cardiac arterial spin labeling technique has been presented, which can be used for accurate perfusion measurements in studies of cardiac disease.

Noninvasive parametric blood flow imaging of head and neck tumours using [15O]H2O and PET/CT

The aim of this study was to develop a simple noninvasive method for measuring blood flow using [15O]H2O PET/CT for the head and neck area applicable in daily clinical practice. Fifteen dynamic [15O]H2O PET emission scans with simultaneous online radioactivity measurements of radial arterial blood [Blood-input functions (IFs)] were performed. Two noninvasively obtained population-based input functions were calculated by averaging all Blood-IF curves corrected for patients' body mass and injected dose [standardized uptake value (SUV)-IF] and for body surface area (BSA-IF) and injected dose. Parametric perfusion images were calculated for each set of IFs using a linearized two-compartment model, and values for several tissues were compared using Blood-IF as the gold standard. On comparing all tissues, the correlation between blood flow obtained with the invasive Blood-IF and both SUV-IF and BSA-IF was significant (R2=0.785 with P<0.001 and R2=0.813 with P<0.001, respectively). In individual tissues, the performance of the two noninvasive methods was most reliable in resting muscle and slightly less reliable in tumour and cerebellar regions. In these two tissues, only BSA-IF showed a significant correlation with Blood-IF (R2=0.307 with P=0.032 in tumours and R2=0.398 with P<0.007 in the cerebellum). The BSA-based noninvasive method enables clinically relevant delineation between areas of low and high blood flow in tumours. The blood flow of low-perfusion tissues can be reliably quantified using either of the evaluated noninvasive methods.

Quantification of regional myocardial blood flow estimation with three-dimensional dynamic rubidium-82 PET and modified spillover correction model

PurposeMyocardial blood flow (MBF) estimation with 82Rubidium (82Rb) positron emission tomography (PET) is technically difficult because of the high spillover between regions of interest, especially due to the long positron range. We sought to develop a new algorithm to reduce the spillover in image-derived blood activity curves, using non-uniform weighted least-squares fitting. MethodsFourteen volunteers underwent imaging with both 3-dimensional (3D) 82Rb and 15O-water PET at rest and during pharmacological stress. Whole left ventricular (LV) 82Rb MBF was estimated using a one-compartment model, including a myocardium-to-blood spillover correction to estimate the corresponding blood input function Ca(t)whole. Regional K1 values were calculated using this uniform global input function, which simplifies equations and enables robust estimation of MBF. To assess the robustness of the modified algorithm, inter-operator repeatability of 3D 82Rb MBF was compared with a previously established method. ResultsWhole LV correlation of 82Rb MBF with 15O-water MBF was better (P < .01) with the modified spillover correction method (r = 0.92 vs r = 0.60). The modified method also yielded significantly improved inter-operator repeatability of regional MBF quantification (r = 0.89) versus the established method (r = 0.82) (P < .01). ConclusionA uniform global input function can suppress LV spillover into the image-derived blood input function, resulting in improved precision for MBF quantification with 3D 82Rb PET.

Image-Derived Blood Input Function from FDG-PET Images in Mice

In a dynamic Positron Emission Tomography (PET) scan, the blood pool (BP) time activity curve forms the input function in a compartmental model technique for evaluation of rate constants to measure myocardial glucose uptake and utilization in vivo. Several methods have been described in the literature for arterial blood sampling, which is the accepted gold standard for measurement of the blood input function [1-3]. A major problem with image-derived blood input function (IDIF) method is that it is susceptible to Spillover (SP) and Partial Volume (PV) effects more so at the early time points due to rapid metabolism and also at the late time points due to cellular trapping of 2-[18F] fluoro-2deoxy-D-glucose (FDG) .

Blood compatible microfluidic system for pharmacokinetic studies in small animals

New radiotracer developments for nuclear medicine imaging require the analysis of blood as a function of time in small animal models. A microfluidic device was developed to monitor the radioactivity concentration in the blood of rats and mice in real time. The microfluidic technology enables a large capture solid angle and a reduction in the separation distance between the sample and detector, thus increasing the detection efficiency. This in turn allows a reduction of the required detection volume without compromising sensitivity, an important advantage with rodent models having a small total blood volume (a few ml). A robust fabrication process was developed to manufacture the microchannels on top of unpackaged p-i-n photodiodes without altering detector performance. The microchannels were fabricated with KMPR, an epoxy-based photoresist similar to SU-8 but with improved resistance to stress-induced fissuring. Surface passivation of the KMPR enables non-diluted whole blood to flow through the channel for up to 20 min at low speed without clotting. The microfluidic device was embedded in a portable blood counter with dedicated electronics, pumping unit and computer control software for utilisation next to a small animal nuclear imaging scanner. Experimental measurements confirmed model predictions and showed a 4- to 19-fold improvement in detection efficiency over existing catheter-based devices, enabling a commensurate reduction in sampled blood volume. A linear dose-response relationship was demonstrated for radioactivity concentrations typical of experiments with rodents. The system was successfully used to measure the blood input function of rats in real time after radiotracer injection.

FDG-PET Quantification of Lung Inflammation with Image-Derived Blood Input Function in Mice

Dynamic FDG-PET imaging was used to study inflammation in lungs of mice following administration of a virulent strain of Klebsiella (K.) pneumoniae. Net whole-lung FDG influx constant (K i) was determined in a compartment model using an image-derived blood input function. Methods. K. pneumoniae (~3 x 105 CFU) was intratracheally administered to six mice with 6 other mice serving as controls. Dynamic FDG-PET and X-Ray CT scans were acquired 24 hr after K. pneumoniae administration. The experimental lung time activity curves were fitted to a 3-compartment FDG model to obtain K i. Following imaging, lungs were excised and immunohistochemistry analysis was done to assess the relative presence of neutrophils and macrophages. Results. Mean K i for control and K. pneumoniae infected mice were (5.1 ± 1.2) ×10−3 versus (11.4 ± 2.0) ×10−3 min−1, respectively, revealing a 2.24 fold significant increase (P = 0.0003) in the rate of FDG uptake in the infected lung. Immunohistochemistry revealed that cellular lung infiltrate was almost exclusively neutrophils. Parametric K i maps by Patlak analysis revealed heterogeneous inflammatory foci within infected lungs. Conclusion. The kinetics of FDG uptake in the lungs of mice can be noninvasively quantified by PET with a 3-compartment model approach based on an image-derived input function.

A pharmacokinetic PET study of NK1 receptor occupancy

There is growing recognition of the importance of integrating drug occupancy data acquired by positron emission tomography (PET) with the plasma pharmacokinetics of the drug, in order to establish proper dose selection in subsequent clinical trials. Here we present a study in human subjects of the occupancy of NK(1) receptors achieved following different doses of casopitant, a selective NK(1) antagonist. Two PET scans were carried out in each of eight human subjects, with the PET radioligand [(11)C]GR205171, a high-affinity and selective NK(1) receptor antagonist. The first scan was under baseline conditions and the second 24 h after a single oral dose of casopitant (2-120 mg). Arterial blood was collected throughout the scans for determination of plasma and whole blood input functions. Venous blood samples were taken prior to and following oral dosing up to 24 h for a pharmacokinetic study of casopitant concentration in plasma. It was first necessary to establish a suitable kinetic model for the estimation of [(11)C]GR205171 NK(1) receptor binding parameters in human brain tissue. A three-tissue compartment model with simultaneous estimation of multiple regions sharing common variables across regions was found suitable for the analysis. Because of the injected cold mass of the tracer and the high affinity of [(11)C]GR205171 a correction for tracer occupancy effects was also incorporated into the analysis. We then developed a pharmacokinetic-receptor occupancy (PK-RO) model of the relationship between casopitant plasma concentrations and receptor binding, using a population approach. These results indicate that after chronic dosing, casopitant can achieve a degree of NK(1) receptor occupancy higher than those that have previously been tested in studies of clinical depression.

Development of a 4D Digital Phantom for Tracer Kinetic Modeling and Analysis of Dynamic Perfusion PET and SPECT Simulation Studies.

The goal is to develop a 4D digital perfusion cardiac-torso (PCAT) phantom, a tracer kinetic extension of the XCAT phantom, by modeling the time activity curves (TACs) of individual organ regions in the phantom for dynamic perfusion PET and SPECT simulation studies. The PCAT phantom is based on a generalized compartmental model, which accepts the blood input function, multiple series or parallel compartments, the bidirectional rate constants between the compartments, the blood volume in the tissue, the extraction curves, and other properties of a specific tracer. Based on the kinetic differential equations of the compartmental model, the TACs of the targeted organ regions were determined. For a specific time point, a voxelized anatomical realistic phantom, which with or without the cardiac and respiratory motions, was generated and the activity concentrations in the organ regions were assigned according to the corresponding TACs. According to the dynamic scanning protocol, multiple phantoms at different acquisition time points, which could have uniform or non-uniform time intervals, were generated. When combining the dynamic phantoms with realistic projection simulator, realistic dynamic projection data could be generated by easily adopting to various scanning protocols and imaging systems. With the availability of the "known truth", the activity map of the targeted organ regions, the TACs, the estimated rate constants and other kinetic parameters, from the projection data and the reconstructed images could be quantitatively evaluated. We demonstrate the usefulness of the 4D PCAT phantom in initial simulation studies in dynamic myocardial perfusion PET imaging with different tracers. The PCAT phantom was found to be an important bridge between the creation of TACs and the generation of simulated projection data. It is a useful simulation tool to study different kinetic analysis methods, acquisition protocols, reconstruction methods, and imaging parameter settings.

Validation of reference tissue modelling for [11C]flumazenil positron emission tomography following head injury

[(11)C]Flumazenil ([(11)C]FMZ) positron emission tomography (PET) can be used as a measure of neuronal loss. The purpose of this study was to validate reference tissue kinetic modelling of [(11)C]FMZ PET within a group of patients with head injury. Following earlier studies, the pons was used as the reference region. PET scans were performed on 16 controls and 11 patients at least 6months following injury, each of whom also had arterial blood sampling to provide whole blood and metabolite-corrected plasma input functions. Regional non-displaceable binding potentials (BP(ND)) were calculated from five reference tissue models and compared to BP(ND) from arterial input models. For the patients, the regions included a peri-lesional region of interest (ROI). Total distribution volume of the pons was not significantly different between control and patient groups (P=0.24). BP(ND) from all the reference tissue approaches correlated well with BP(ND) from the plasma input models for both controls (r (2)=0.98-1.00; P<0.001) and patients (r (2)=0.99-1.00; P<0.001). For the peri-lesional regions (n=11 ROI values), the correlation was also high (r (2)=0.91). These results indicate that reference tissue modelling with the pons as the reference region is valid for [(11)C]FMZ PET in head-injured patients at 6months following injury within both normal appearing and peri-lesional brain regions.

Longitudinal Evaluation of Fatty Acid Metabolism in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic MicroSPECT Imaging

The goal of this project is to develop radionuclide molecular imaging technologies using a clinical pinhole SPECT/CT scanner to quantify changes in cardiac metabolism using the spontaneously hypertensive rat (SHR) as a model of hypertensive-related pathophysiology. This paper quantitatively compares fatty acid metabolism in hearts of SHR and Wistar-Kyoto normal rats as a function of age and thereby tracks physiological changes associated with the onset and progression of heart failure in the SHR model. The fatty acid analog, 123I-labeled BMIPP, was used in longitudinal metabolic pinhole SPECT imaging studies performed every seven months for 21 months. The uniqueness of this project is the development of techniques for estimating the blood input function from projection data acquired by a slowly rotating camera that is imaging fast circulation and the quantification of the kinetics of 123I-BMIPP by fitting compartmental models to the blood and tissue time-activity curves.

Propagation of Blood Function Errors to the Estimates of Kinetic Parameters with Dynamic PET

Dynamic PET, in contrast to static PET, can identify temporal variations in the radiotracer concentration. Mathematical modeling of the tissue of interest in dynamic PET can be simplified using compartment models as a linear system where the time activity curve of a specific tissue is the convolution of the tracer concentration in the plasma and the impulse response of the tissue containing kinetic parameters. Since the arterial sampling of blood to acquire the value of tracer concentration is invasive, blind methods to estimate both blood input function and kinetic parameters have recently drawn attention. Several methods have been developed, but the effect of accuracy of the estimated blood function on the estimation of the kinetic parameters is not studied. In this paper, we present a method to compute the error in the kinetic parameter estimates caused by the error in the blood input function. Computer simulations show that analytical expressions we derive are sufficiently close to results obtained from numerical methods. Our findings are important to observe the effect of the blood function on kinetic parameter estimation, but also useful to evaluate various blind methods and observe the dependence of kinetic parameter estimates to certain parts of the blood function.

Simplified [ 18 F]FDG Image-Derived Input Function Using the Left Ventricle, Liver, and One Venous Blood Sample

A relatively simple, almost entirely noninvasive imaging-based method is presented for deriving arterial blood input functions for quantitative [(18)F]2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomographic (PET) studies in rodents. It requires only one venous blood sample at the end of the scan. MicroPET images and arterial blood time-activity curves (TACs) were downloaded from the Mouse Quantitation Program database at the University of California, Los Angeles. Three-dimensional regions of interest were drawn around the blood-pool region of the left ventricle and within the liver to derive their respective TACs. To construct the "hybrid" image-derived input function (IDIF), the initial part of the left ventricle TAC, containing the peak concentration of [(18)F]FDG in the arterial blood, was corrected for spillout (ie, partial-volume effect yielding a recovery coefficient < 1) and then joined to the liver TAC (normalized to the 60-minute arterial blood sample) immediately after it peaks. To validate our method, the [(18)F]FDG influx constant (K(i)) was estimated using a two-tissue compartment model and compared to estimates of K(i) obtained using measured arterial blood TACs. No significant difference in the K(i) estimates was obtained with the arterial blood input function and our hybrid IDIF. We conclude that the normalized hybrid IDIF can be used in practice to obtain reliable K(i) estimates.

Comparison of Tumor Volumes Derived from Glucose Metabolic Rate Maps and SUV Maps in Dynamic 18F-FDG PET

Tumor delineation using noninvasive medical imaging modalities is important to determine the target volume in radiation treatment planning and to evaluate treatment response. It is expected that combined use of CT and functional information from 18F-FDG PET will improve tumor delineation. However, until now, tumor delineation using PET has been based on static images of 18F-FDG standardized uptake values (SUVs). 18F-FDG uptake depends not only on tumor physiology but also on blood supply, distribution volume, and competitive uptake processes in other tissues. Moreover, 18F-FDG uptake in tumor tissue and in surrounding healthy tissue depends on the time after injection. Therefore, it is expected that the glucose metabolic rate (MRglu) derived from dynamic PET scans gives a better representation of the tumor activity than does SUV. The aim of this study was to determine tumor volumes in MRglu maps and to compare them with the values from SUV maps. Twenty-nine lesions in 16 dynamic 18F-FDG PET scans in 13 patients with non-small cell lung carcinoma were analyzed. MRglu values were calculated on a voxel-by-voxel basis using the standard 2-compartment 18F-FDG model with trapping in the linear approximation (Patlak analysis). The blood input function was obtained by arterial sampling. Tumor volumes were determined in SUV maps of the last time frame and in MRglu maps using 3-dimensional isocontours at 50% of the maximum SUV and the maximum MRglu, respectively. Tumor volumes based on SUV contouring ranged from 1.31 to 52.16 cm3, with a median of 8.57 cm3. Volumes based on MRglu ranged from 0.95 to 37.29 cm3, with a median of 3.14 cm3. For all lesions, the MRglu volumes were significantly smaller than the SUV volumes. The percentage differences (defined as 100% x (V MRglu - V SUV)/V SUV, where V is volume) ranged from -12.8% to -84.8%, with a median of -32.8%. Tumor volumes from MRglu maps were significantly smaller than SUV-based volumes. These findings can be of importance for PET-based radiotherapy planning and therapy response monitoring.

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

The liver is perfused through the portal vein and the hepatic artery. When its perfusion is assessed using positron emission tomography (PET) and (15)O-labeled water (H(2) (15)O), 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 H(2) (15)O PET images with a completely non-invasive approach. 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. 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). In conclusion, our results demonstrate that DIF can be estimated directly from tissue curves obtained through H(2) (15)O PET imaging. This suggests the possibility to enable completely non-invasive technique to assess liver perfusion in patho-physiological studies.

An investigation of temporal regularization techniques for dynamic PET reconstructions using temporal splines

The use of a temporal B-spline basis for the reconstruction of dynamic positron emission tomography data was investigated. Maximum likelihood (ML) reconstructions using an expectation maximization framework and maximum A-posteriori (MAP) reconstructions using the generalized expectation maximization framework were evaluated. Different parameters of the B-spline basis of such as order, number of basis functions and knot placing were investigated in a reconstruction task using simulated dynamic list-mode data. We found that a higher order basis reduced both the bias and variance. Using a higher number of basis functions in the modeling of the time activity curves (TACs) allowed the algorithm to model faster changes of the TACs, however, the TACs became noisier. We have compared ML, Gaussian postsmoothed ML and MAP reconstructions. The noise level in the ML reconstructions was controlled by varying the number of basis functions. The MAP algorithm penalized the integrated squared curvature of the reconstructed TAC. The postsmoothed ML was always outperformed in terms of bias and variance properties by the MAP and ML reconstructions. A simple adaptive knot placing strategy was also developed and evaluated. It is based on an arc length redistribution scheme during the reconstruction. The free knot reconstruction allowed a more accurate reconstruction while reducing the noise level especially for fast changing TACs such as blood input functions. Limiting the number of temporal basis functions combined with the adaptive knot placing strategy is in this case advantageous for regularization purposes when compared to the other regularization techniques.

T1 measurement of flowing blood and arterial input function determination for quantitative 3D T1‐weighted DCE‐MRI

To propose a simple, accurate method for measuring T(1) in flowing blood and the arterial input function (AIF), and to evaluate the impact on dynamic contrast-enhanced MRI (DCE-MRI) quantification of pharmacokinetic parameters. A total of 10 rabbits were scanned at 1.5 Tesla and administered a bolus of Gadomer. Preinjection T(1) and AIF measurements were acquired in the iliac arteries using a rapid three-dimensional (3D) spoiled gradient recalled echo (SPGR) approach. Correction was made for imperfect B(1) fields, in-flow, and partial volume effects. DCE-MRI parameters blood volume (v(b)) and endothelial transfer constant (K(trans)) in resting skeletal muscle were estimated from pharmacokinetic analysis using individually measured AIFs. Literature comparisons were made to assess accuracy. Blood T(1) was more accurate and precise after correction for B(1) and partial volume errors (1267 +/- 72 msec). Measured AIFs followed reported biexponential decay characteristics for Gadomer clearance in rabbits. Parameters v(b) (2.47 +/- 0.65%) and K(trans) (3.6 +/- 1.0 x 10(-3) minute(-1)) derived from AIFs based on corrected blood T(1)s were more reproducible and in better agreement with literature values. The proposed method enables accurate in vivo blood T(1) and AIF measurements and can be easily implemented in a range of DCE-MRI applications to improve both the accuracy and reproducibility of pharmacokinetic parameters.