Mark Lubberink

Misalignment between PET and low-dose CT (LD-CT) can cause severe artifacts in cardiac PET/CT because of attenuation-correction errors, even when using slow or cine LD-CT. Myocardial blood flow (MBF), as measured by ¹⁵O-water, can be determined from the rate of ¹⁵O-water washout from myocardial tissue, which is independent of tissue attenuation. The purpose of the present study was to assess the accuracy of these MBF measurements in the absence of attenuation correction. Methods: Twenty-five patients referred for evaluation of myocardial perfusion underwent 6-min rest and adenosine stress PET scans after the administration of 370 MBq of ¹⁵O-water; both scans were followed by slow LD-CT. Data were acquired on a PET/CT scanner and reconstructed by a 3-dimensional row-action maximum likelihood algorithm both with (CTAC) and without (NAC) attenuation correction. An ascending aorta volume of interest was used as input function. MBF and coronary flow reserve (CFR) were calculated for 17 myocardial segments using nonlinear regression of the standard single-tissue-compartment model with corrections for left and right ventricular spillover and perfusable tissue fraction. Results: High correlation (r² = 0.99 and 0.97, with slopes of 0.96 and 0.91 for rest and stress, respectively) and excellent agreement (intraclass correlation coefficient [ICC], 1.00 and 0.98) between NAC- and CTAC-based MBF values were found. Absolute rest and stress MBF values were 3% and 8%, respectively, lower for NAC scans. The correlation coefficient between all NAC and CTAC CFR values was 0.95 (ICC, 0.95; slope, 0.92) and 0.97 (ICC, 0.99; slope, 1.01) when only CFR values below 2 were considered. Deviations between CTAC and NAC values were smallest for basal segments and increased toward the apex. Conclusion: MBF and CFR can be measured accurately using ¹⁵O-water and PET without correcting for attenuation, reducing the effective dose to the patient to 0.8 mSv for a complete rest–stress protocol. This dose is an order of magnitude lower than typical values for ⁸²Rb, ^99mTc-methoxyisobutylisonitrile, or CT perfusion scans.

Background: In vitro data suggest that changes in myocardial substrate metabolism may contribute to impaired myocardial function in diabetic cardiomyopathy (DCM). The purpose of the present study was to study in a rat model of early DCM, in vivo changes in myocardial substrate metabolism and their association with myocardial function. Methods: Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats underwent echocardiography followed by [¹¹C]palmitate positron emission tomography (PET) under fasting, and [¹⁸F]-2-fluoro-2-deoxy-D-glucose PET under hyperinsulinaemic euglycaemic clamp conditions. Isolated cardiomyocytes were used to determine isometric force development. Results: PET data showed a 66% decrease in insulin-mediated myocardial glucose utilisation and a 41% increase in fatty acid (FA) oxidation in ZDF vs. ZL rats (both p < 0.05). Echocardiography showed diastolic and systolic dysfunction in ZDF vs. ZL rats, which was paralleled by a significantly decreased maximal force (68%) and maximal rate of force redevelopment (69%) of single cardiomyocytes. Myocardial functional changes were significantly associated with whole-body insulin sensitivity and decreased myocardial glucose utilisation. ZDF hearts showed a 68% decrease in glucose transporter-4 mRNA expression (p < 0.05), a 22% decrease in glucose transporter-4 protein expression (p = 0.10), unchanged levels of pyruvate dehydrogenase kinase-4 protein expression, a 57% decreased phosphorylation of AMP activated protein kinase α1/2 (p < 0.05) and a 2.4-fold increased abundance of the FA transporter CD36 to the sarcolemma (p < 0.01) vs. ZL hearts, which are compatible with changes in substrate metabolism. In ZDF vs. ZL hearts a 2.4-fold reduced insulin-mediated phosphorylation of Akt was found (p < 0.05). Conclusion: Using PET and echocardiography, we found increases in myocardial FA oxidation with a concomitant decrease of insulin-mediated myocardial glucose utilisation in early DCM. In addition, the latter was associated with impaired myocardial function. These in vivo data expand previous in vitro findings showing that early alterations in myocardial substrate metabolism contribute to myocardial dysfunction.

Iodine-124 is a positron-emitting iodine isotope, enabling measurement of iodine uptake using positron emission tomography (PET). There is a number of situations where the use of (124)I-PET/computed tomography (CT) can improve the current clinical practice in the diagnosis and treatment of thyroid cancer. Firstly, (124)I-PET/CT can aid in the staging of patients, because of better detection of metastatic disease and measurement of metabolic tumour volume, and thus separate low-risk from high risk patients. Secondly, the much higher sensitivity and spatial resolution of PET compared to gamma scintigraphy can also improve detection of recurrent disease. Furthermore, (124)I-PET can be used for patient-specific radioiodine therapy radiation dosimetry. Simultaneous administration of the therapeutic dose of (131)I and a tracer dose of (124)I allows for accurate measurement of iodine uptake during therapy. The decay scheme of (124)I, with few positrons and many gamma rays emitted per decay, often simultaneously, poses a challenge to quantitative PET imaging. Improved correction methods and the use of last-generation PET/CT scanners with faster electronics and better energy resolution can overcome this.

Diminished P-glycoprotein ( P-gp)-mediated transport across the Blood–brain barrier may play an important role in several neurodegenerative disorders. In previous studies, a racemic mixture of ( R)-[¹¹C]verapamil and ( S)-[¹¹C]verapamil has been used as tracer for assessing P-gp function using positron emission tomography (PET). Quantification, however, is compromised by potential differences in kinetics between these two isomers. The aim of the present study was to evaluate the kinetics of pure ( R)-[¹¹C]verapamil in humans and to develop a tracer kinetic model for the analysis of P-gp-mediated transport of ( R)-[¹¹C]verapamil, including the putative contribution of its radioactive metabolites. Dynamic ( R)-[¹¹C]verapamil PET scans of 10 male volunteers were analysed with various single- or two-tissue compartment models, with separate compartments for N-dealkylated and N-demethylated metabolites, assuming that either ( R)-[¹¹C]verapamil alone or ( R)-[¹¹C]verapamil and any combination of metabolites cross the BBB. In addition, six of the subjects underwent two ( R)-[¹¹C]verapamil scans to evaluate test–retest reliability. One hour after injection, 50% of total plasma radioactivity consisted of labelled metabolites. Most models fitted the data well and the analysis did not point to a definite ‘best’ model, with differences in optimal model between subjects. The lowest mean test–retest variability (2.9%) was found for a single-tissue model without any metabolite correction. Models with separate metabolite compartments lead to high test–retest variability. Assuming that differences in kinetics of ( R)-[¹¹C]verapamil and N-dealkylated metabolites are small, a one input, one-tissue model with correction for N-demethylated metabolites only leads to a good compromise between fit quality and test–retest variability.

Radiation dosimetry of thyroid cancer therapy with 131I can be performed by coadministration of 124I followed by longitudinal PET scans over several days. The photons emitted by 131I may affect PET image quality. The aim of this study was to assess the influence of large amounts of 131I on PET image quality and accuracy with various acquisition settings. Noise equivalent count (NEC) rates of 124I only were measured with a standard clinical PET scanner. Apart from the standard 350- to 650-keV energy window, 425- to 650-keV and 460- to 562-keV windows were used and data were acquired both with (2-dimensional) and without (3-dimensional [3D]) septa. A phantom containing 6 hot spheres, filled with a combination of 131I and 124I and with a sphere-to-background ratio of 18:1, was scanned repeatedly with energy window settings as indicated and emission and transmission scan durations of 7 and 3 min, respectively. NEC rates were calculated and compared with those measured with the phantom filled with only 124I. Sphere-to-background ratios in the reconstructed images were determined. One patient with known metastatic thyroid cancer was scanned using energy window settings and scan times as indicated 3 and 6 d after administration of 5.5 GBq of 131I and 75 MBq of 124I. The highest 124I-only NEC rates were obtained using a 425- to 650-keV energy window in 3D mode. In the presence of (131)I, the settings giving the highest NEC rate and contrast were 425-650 keV and 460-562 keV in 3D mode, with the clinical scans giving the highest quality images with the same settings. Acquisition in 3D mode with a 425- to 650-keV or 460- to 562-keV window leads to the highest image quality and contrast when imaging 124I in the presence of large amounts of 131I using a standard clinical PET scanner.

Background: Positron emission tomography (PET) is a powerful imaging technique with the potential of obtaining functional or biochemical information by measuring distribution and kinetics of radiolabelled molecules in a biological system, bothin vitroandin vivo. PET images can be used directly or after kinetic modelling to extract quantitative values of a desired physiological, biochemical or pharmacological entity. Because such images are generally noisy, it is essential to understand how noise affects the derived quantitative values. A pre-requisite for this understanding is that the properties of noise such as variance (magnitude) and texture (correlation) are known.Methods: In this paper we explored the pattern of noise correlation in experimentally generated PET images, with emphasis on the angular dependence of correlation, using the autocorrelation function (ACF). Experimental PET data were acquired in 2D and 3D acquisition mode and reconstructed by analytical filtered back projection (FBP) and iterative ordered subsets expectation maximisation (OSEM) methods. The 3D data was rebinned to a 2D dataset using FOurier REbinning (FORE) followed by 2D reconstruction using either FBP or OSEM. In synthetic images we compared the ACF results with those from covariance matrix. The results were illustrated as 1D profiles and also visualized as 2D ACF images.Results: We found that the autocorrelation images from PET data obtained after FBP were not fully rotationally symmetric or isotropic if the object deviated from a uniform cylindrical radioactivity distribution. In contrast, similar autocorrelation images obtained after OSEM reconstruction were isotropic even when the phantom was not circular. Simulations indicated that the noise autocorrelation is non-isotropic in images created by FBP when the level of noise in projections is angularly variable. Comparison between 1D cross profiles on autocorrelation images obtained by FBP reconstruction and covariance matrices produced almost identical results in a simulation study.Conclusion: With asymmetric radioactivity distribution in PET, reconstruction using FBP, in contrast to OSEM, generates images in which the noise correlation is non-isotropic when the noise magnitude is angular dependent, such as in objects with asymmetric radioactivity distribution. In this respect, iterative reconstruction is superior since it creates isotropic noise correlations in the images.

The aim of this work was to compare the quantitative accuracy of iteratively reconstructed cardiac (18)F-FDG PET with that of filtered backprojection for both 2-dimensional (2D) and 3-dimensional (3D) acquisitions and to establish an optimal procedure for imaging myocardial viability with (18)F-FDG PET. Eight patients underwent dynamic cardiac (18)F-FDG PET using an interleaved 2D/3D scan protocol, enabling comparison of 2D and 3D acquisitions within the same patient and study. A 10-min transmission scan was followed by a 10-min, 25-frame dynamic 3D scan and then by a series of 10 alternating 5-min 3D and 2D scans. Images were reconstructed with filtered backprojection (FBP) or attenuation-weighted ordered-subsets expectation maximization (OSEM), combined with Fourier rebinning (FORE) for 3D acquisitions, applying all usual corrections. Regions of interest (ROIs) were drawn in the myocardium, left ventricle, and ascending aorta, with the last 2 being used to define image-derived input functions (IDIFs). Patlak graphical analysis was used to compare net (18)F-FDG uptake in the myocardium, calculated from either 2D or 3D data, after reconstruction with FBP or OSEM. Either IDIFs or arterial sampling was used as the input function. The same analysis was performed on parametric images. A good correlation (r(2) > 0.99) was found between net (18)F-FDG uptake values for a myocardium ROI determined using each acquisition and reconstruction method and blood-sampling input functions. A similar result was found for parametric images. The ascending aorta was the best choice for IDIF definition. Good correlation and no bias of net (18)F-FDG uptake in relation to that based on FBP images, combined with less image noise, make 3D acquisition with FORE plus attenuation-weighted OSEM reconstruction the preferred choice for cardiac (18)F-FDG PET studies.

A spatially variant convolution subtraction scatter correction was developed for a Hamamatsu SHR-7700 animal PET scanner. This scanner, with retractable septa and a gantry that can be tilted 90°, was designed for studies of conscious monkeys. The implemented dual-exponential scatter kernel takes into account both radiation scattered inside the object and radiation scattered in gantry and detectors. This is necessary because of the relatively large contribution of gantry and detector scatter in this scanner. The correction is used for scatter correction of emission as well as transmission data. Transmission scatter correction using the dual-exponential kernel leads to a measured attenuation coefficient of 0.096 cm⁻¹ in water, compared to 0.089 cm⁻¹ without scatter correction. Scatter correction on both emission and transmission data resulted in a residual correction error of 2.1% in water, as well as improved image contrast and hot spot quantification.