Non-invasive kinetic modelling of PET tracers with radiometabolites using a constrained simultaneous estimation method: evaluation with 11C-SB201745.

BACKGROUND: Kinetic analysis of dynamic PET data requires an accurate knowledge of available PET tracer concentration within blood plasma over time, known as the arterial input function (AIF). The gold standard method used to measure the AIF requires serial arterial blood sampling over the course of the PET scan, which is an invasive procedure and makes this method less practical in clinical settings. Traditional image-derived methods are limited to specific tracers and are not accurate if metabolites are present in the plasma. RESULTS: In this work, we utilise an image-derived whole blood curve measurement to reduce the computational complexity of the simultaneous estimation method (SIME), which is capable of estimating the AIF directly from tissue time activity curves (TACs). This method was applied to data obtained from a serotonin receptor study (11C-SB207145) and estimated parameter results are compared to results obtained using the original SIME and gold standard AIFs derived from arterial samples. Reproducibility of the method was assessed using test-retest data. It was shown that the incorporation of image-derived information increased the accuracy of total volume of distribution (V T) estimates, averaged across all regions, by 40% and non-displaceable binding potential (BP ND) estimates by 16% compared to the original SIME. Particular improvements were observed in K1 parameter estimates. BP ND estimates, based on the proposed method and the gold standard arterial sample-derived AIF, were not significantly different (P=0.7). CONCLUSIONS: The results of this work indicate that the proposed method with prior AIF information obtained from a partial volume corrected image-derived whole blood curve, and modelled parent fraction, has the potential to be used as an alternative non-invasive method to perform kinetic analysis of tracers with metabolite products

Acute hypoxia increases the cerebral metabolic rate:a magnetic resonance imaging study

The aim of the present study was to examine changes in cerebral metabolism by magnetic resonance imaging of healthy subjects during inhalation of 10% O(2) hypoxic air. Hypoxic exposure elevates cerebral perfusion, but its effect on energy metabolism has been less investigated. Magnetic resonance imaging techniques were used to measure global cerebral blood flow and the venous oxygen saturation in the sagittal sinus. Global cerebral metabolic rate of oxygen was quantified from cerebral blood flow and arteriovenous oxygen saturation difference. Concentrations of lactate, glutamate, N-acetylaspartate, creatine and phosphocreatine were measured in the visual cortex by magnetic resonance spectroscopy. Twenty-three young healthy males were scanned for 60 min during normoxia, followed by 40 min of breathing hypoxic air. Inhalation of hypoxic air resulted in an increase in cerebral blood flow of 15.5% (p = 0.058), and an increase in cerebral metabolic rate of oxygen of 8.5% (p = 0.035). Cerebral lactate concentration increased by 180.3% ([Formula: see text]), glutamate increased by 4.7% ([Formula: see text]) and creatine and phosphocreatine decreased by 15.2% (p [Formula: see text]). The N-acetylaspartate concentration was unchanged (p = 0.36). In conclusion, acute hypoxia in healthy subjects increased perfusion and metabolic rate, which could represent an increase in neuronal activity. We conclude that marked changes in brain homeostasis occur in the healthy human brain during exposure to acute hypoxia

Fritz-Hansen T. Quantification of the effect of water exchange in dynamic contrast MRI perfusion measurements

Measurement of myocardial and brain perfusion when using exogenous contrast agents (CAs) such as gadolinium-DTPA (Gd-DTPA) and MRI is affected by the diffusion of water between compartments. This water exchange may have an impact on signal enhancement, or, equivalently, on the longitudinal relaxation rate, and could therefore cause a systematic error in the calculation of perfusion (F) or the perfusionrelated parameter, the unidirectional influx constant over the capillary membranes (K i ). The aim of this study was to quantify the effect of water exchange on estimated perfusion (F or K i ) by using a realistic simulation. These results were verified by in vivo studies of the heart and brain in humans. The conclusion is that water exchange between the vascular and extravascular extracellular space has no effect on K i estimation in the myocardium when a normal dose of Gd-DTPA is used. Water exchange can have a significant effect on perfusion estimation (F) in the brain when using Gd-DTPA, where it acts as an intravascular contrast agent. Measurement of perfusion when using exogenous contrast agents (CAs) and MRI is affected by the diffusion of water between compartments. Several studies have indicated that this could affect the results of such perfusion measurements (1-6). However, contrast-enhanced MRI using T 1 -weighted imaging has been developed in order to measure perfusion or perfusion-related parameters of the heart in vivo without explicitly considering the effect of water exchange. Models of perfusion in animals and humans when using extravascular CAs such as gadolinium-DTPA (Gd-DTPA) or intravascular CA have been presented (7-12). These measurements are often based on inversion recovery turboFLASH (IR-turboFLASH) or saturation recovery turboFLASH (SAT-turboFLASH) imaging. Most of these studies measure the tissue enhancement curve and the arterial input function and rely on basic tracer kinetic models as formulated by Kety (13). In the ideal case, this approach gives the unidirectional influx constant K i (ml/100 g/min) for CA diffusion over the capillary membrane when extravascular CA is used and the perfusion F (ml/100 g/min) when intravascular CA is used. For extravascular CA, the perfusion and the unidirectional influx constant are related by K i ϭ EF There is now growing evidence that K i in particular provides valuable and clinically useful information related to perfusion (7-12,15). For example, it has been shown previously that infusion of dipyridamole in humans resulted in an increase of K i by a factor of 2-3 in the heart of healthy subjects. In patients with ischemic heart disease, K i was either unaffected or decreased after infusion of dipyridamole in areas supplied by an insufficient coronary artery Many assumptions need to be investigated in order to clearly associate directly the MRI-determined K i with the physiological parameter, the unidirectional influx constant of the CA diffusion over the capillary membrane in the heart. One of the main concerns is related to the fact that CA is measured indirectly through water relaxation. Water diffuses between compartments and this exchange of water between compartments can modify the MR signal enhancement of the tissue (1) and, therefore, influence the measured K i . Hence, water exchange can potentially affect the results obtained with both extravascular and intravascular CA. This study investigates quantitatively the effect of water exchange between intravascular and extravascular compartments and focuses on the effect on K i when using an extravascular CA and the effect on perfusion (F) when using an intravascular CA. The effect of water exchange was quantified by computer simulations. First, a simple approach was used by simulating two extreme situations: the fast water exchange regime, defined as 1/ ӷ ͉1/T 1b Ϫ 1/T 1myo ͉ and the no (or very slow) water exchange regime, defined as 1/ Ӷ ͉1/T 1b Ϫ 1/T 1myo ͉, where 1/ ϭ 1/ b ϩ 1/ myo with b and myo being the average residence times of water in the vascular and extravascular compartments, respectively, T 1b denotes blood longitudinal relaxation time, and T 1myo denotes myocardial longitudinal relaxation time (2). Second, using a specified MR sequence a two-site exchange model was incorporated into the perfusion model, allowing us to estimate how dependent K i or F was on the water exchange rate between compartments. In order to validate the predicted results of this model, we performed perfusion measurements using Gd-DTPA in the heart, where Gd-DTPA acts as an extravascular CA, and in the brain, where Gd-DTPA acts as an intravascular CA in normal volunteers (we did not have access to intravascular CA for the heart). The nomenclature in MR tracer kinetic models is somewhat confusing and in the following we will define transfer constants and concentrations carefully and adhere a

Non-invasive kinetic modelling of PET tracers with radiometabolites using a constrained simultaneous estimation method: evaluation with 11C-SB201745.

BACKGROUND: Kinetic analysis of dynamic PET data requires an accurate knowledge of available PET tracer concentration within blood plasma over time, known as the arterial input function (AIF). The gold standard method used to measure the AIF requires serial arterial blood sampling over the course of the PET scan, which is an invasive procedure and makes this method less practical in clinical settings. Traditional image-derived methods are limited to specific tracers and are not accurate if metabolites are present in the plasma. RESULTS: In this work, we utilise an image-derived whole blood curve measurement to reduce the computational complexity of the simultaneous estimation method (SIME), which is capable of estimating the AIF directly from tissue time activity curves (TACs). This method was applied to data obtained from a serotonin receptor study (11C-SB207145) and estimated parameter results are compared to results obtained using the original SIME and gold standard AIFs derived from arterial samples. Reproducibility of the method was assessed using test-retest data. It was shown that the incorporation of image-derived information increased the accuracy of total volume of distribution (V T) estimates, averaged across all regions, by 40% and non-displaceable binding potential (BP ND) estimates by 16% compared to the original SIME. Particular improvements were observed in K1 parameter estimates. BP ND estimates, based on the proposed method and the gold standard arterial sample-derived AIF, were not significantly different (P=0.7). CONCLUSIONS: The results of this work indicate that the proposed method with prior AIF information obtained from a partial volume corrected image-derived whole blood curve, and modelled parent fraction, has the potential to be used as an alternative non-invasive method to perform kinetic analysis of tracers with metabolite products

Hybrid PET/MRI imaging in healthy unsedated newborn infants with quantitative rCBF measurements using ¹⁵O-water PET

In this study, a new hybrid PET/MRI method for quantitative regional cerebral blood flow (rCBF) measurements in healthy newborn infants was assessed and the low values of rCBF in white matter previously obtained by arterial spin labeling (ASL) were tested. Four healthy full-term newborn subjects were scanned in a PET/MRI scanner during natural sleep after median intravenous injection of 14 MBq15O-water. Regional CBF was quantified using a one-tissue-compartment model employing an image-derived input function (IDIF) from the left ventricle. PET rCBF showed the highest values in the thalami, mesencephalon and brain stem and the lowest in cortex and unmyelinated white matter. The average global CBF was 17.8 ml/100 g/min. The average frontal and occipital unmyelinated white matter CBF was 10.3 ml/100 g/min and average thalamic CBF 31.3 ml/100 g/min. The average white matter/thalamic ratio CBF was 0.36, significantly higher than previous ASL data. The rCBF ASL measurements were all unsuccessful primarily owing to subject movement. In this study, we demonstrated for the first time, a minimally invasive PET/MRI method using low activity15O-water PET for quantitative rCBF assessment in unsedated healthy newborn infants and found a white/grey matter CBF ratio similar to that of the adult human brain.</jats:p

Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study

Neuro Imaging Researc