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Diseases of ectopic calcification of the vascular wall range from lethal orphan diseases such as generalized arterial calcification of infancy (GACI), to common diseases such as hardening of the arteries associated with aging and calciphylaxis of chronic kidney disease (CKD). GACI is a lethal orphan disease in which infants calcify the internal elastic lamina of their medium and large arteries and expire of cardiac failure as neonates, while calciphylaxis of CKD is a ubiquitous vascular calcification in patients with renal failure. Both disorders are characterized by vascular Mönckeburg’s sclerosis accompanied by decreased concentrations of plasma inorganic pyrophosphate (PP i ). Here we demonstrate that subcutaneous administration of an ENPP1-Fc fusion protein prevents the mortality, vascular calcifications and sequela of disease in animal models of GACI, and is accompanied by a complete clinical and biomarker response. Our findings have implications for the treatment of rare and common diseases of ectopic vascular calcification. Generalized arterial calcification of infancy (GACI) is a terminal disease caused by the ENPP1 enzyme deficiency. Here, Albrigh et al . show that ENPP1 enzyme replacement therapy prevents the ectopic calcifications and mortality in mice with GACI, suggesting a novel treatment for vascular calcification in humans.

The reasons are clear: (1) topics covered in the Annual Meeting have proliferated (now including multiple aspects of molecular imaging); (2) no one person can attend all of the scientific presentations of interest and still find time to visit posters, exhibitors, and special events as well as attend important meetings; and (3) attendees coming to the Annual Meeting are grateful to receive an overview of the important directions and innovations covered in the summary sessions by experts in their respective fields. With more and more booths displaying instruments and services from a growing international world stage, the Exhibitors' Hall provides a one-of-a-kind current view on the state of the art in preclinical and clinical research and medical care in our field.

PurposeThis joint practice guideline or procedure standard was developed collaboratively by the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). The goal of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of dopaminergic imaging in parkinsonian syndromes.MethodsCurrently nuclear medicine investigations can assess both presynaptic and postsynaptic function of dopaminergic synapses. To date both EANM and SNMMI have published procedural guidelines for dopamine transporter imaging with single photon emission computed tomography (SPECT) (in 2009 and 2011, respectively). An EANM guideline for D2 SPECT imaging is also available (2009). Since the publication of these previous guidelines, new lines of evidence have been made available on semiquantification, harmonization, comparison with normal datasets, and longitudinal analyses of dopamine transporter imaging with SPECT. Similarly, details on acquisition protocols and simplified quantification methods are now available for dopamine transporter imaging with PET, including recently developed fluorinated tracers. Finally, [18F]fluorodopa PET is now used in some centers for the differential diagnosis of parkinsonism, although procedural guidelines aiming to define standard procedures for [18F]fluorodopa imaging in this setting are still lacking.ConclusionAll these emerging issues are addressed in the present procedural guidelines for dopaminergic imaging in parkinsonian syndromes.

Reliable quantitative dopamine transporter imaging is critical for early and accurate diagnosis of Parkinson's disease (PD). Image quantitation is made difficult by the variability introduced by manual interventions during the quantitative processing steps. A fully automated objective striatal analysis (OSA) program was applied to dopamine transporter images acquired from PD subjects with early symptoms of suspected parkinsonism and compared with manual analysis by a trained image-processing technologist. A total of 101 (123)I-beta-CIT SPECT scans were obtained of subjects recruited to participate in the Query-PD Study. Data were reconstructed and then analyzed according to a package of scripts (OSA) that reorients the SPECT brain volume to the standard geometry of an average scan, automatically locates the striata and occipital structures, locates the caudate and putamen, and calculates the background-subtracted striatal uptake ratio (V3''). The striatal uptake ratio calculated by OSA was compared with manual analysis by a trained image-processing technologist. Several parameters were varied in the automated analysis, including the number of summed transverse slices and the size and separation of the regions of interest applied to the caudate and putamen to determine the optimum OSA analysis. The parameters giving V3'' with the closest correlation to the manual analysis were accepted as optimal. The optimal comparison between the V3'' obtained by the human analyst and that obtained by the automated OSA analysis yielded a correlation coefficient of 0.96. Our optimized OSA delivers V3'' evaluations that closely correlate with a similar evaluation manually applied by a highly trained image-processing technologist.

Are “generalized” seizures truly generalized? Generalized tonic–clonic seizures are classified as either secondarily generalized with local onset or primarily generalized, without known focal onset. In both types of generalized seizures widespread regions of the nervous system engage in abnormally synchronous and high-frequency neuronal firing. However, emerging evidence suggests that all neurons are not homogeneously involved; specific nodes within the network may be crucial for the propagation and behavioral manifestations of generalized tonic–clonic seizures. Study of human tonic–clonic seizures has been limited by problems with patient movement and variable seizure types. To circumvent these problems, we imaged generalized tonic–clonic seizures during electroconvulsive therapy, in which seizure type and timing are well controlled. 99mTc-hexamethylpropylene amine oxime injections during seizures provide a “snapshot” of cerebral blood flow that can be imaged by single photon emission computed tomography (SPECT) after seizure termination. Here we show that focal regions of frontal and parietal association cortex show the greatest relative signal increases. Involvement of the higher-order association cortex may explain the profound impairment of consciousness seen in generalized seizures. In addition, focal involvement of the dominant temporal lobe was associated with impaired retrograde verbal memory. Similar focal increases were also seen in imaging of spontaneous secondarily generalized tonic–clonic seizures. Relative sparing of many brain regions during both spontaneous and induced seizures suggests that specific networks may be more important than others in so-called generalized seizures.

The purposes of this study were to develop a method for nonuniform attenuation correction of 123I emission brain images based on transmission imaging with a longer-lived isotope (i.e., 57Co) and to evaluate the relative improvement in quantitative SPECT images achieved with nonuniform attenuation correction. Emission and transmission SPECT scans were acquired on three different sets of studies: a heterogeneous brain phantom filled with 1231 to simulate the distribution of dopamine transporters labeled with 2beta-carbomethoxy-3beta-(4-123I-iodophenyl)tropane (123I-beta-CIT); nine healthy human control subjects who underwent transmission scanning using two separate line sources (57Co and 123I); and a set of eight patients with Parkinson's disease and five healthy control subjects who received both emission and transmission scans after injection of 123I-beta-CIT. Attenuation maps were reconstructed using a Bayesian transmission reconstruction algorithm, and attenuation correction was performed using Chang's postprocessing method. The spatial distribution of errors within the brain was obtained from attenuation correction factors computed from uniform and nonuniform attenuation maps and was visualized on a pixel-by-pixel basis as an error image. For the heterogeneous brain phantom, the uniform attenuation correction had errors of 2%-6.5% for regions corresponding to striatum and background, whereas nonuniform attenuation correction was within 1%. Analysis of 123I transmission images of the nine healthy human control subjects showed differences between uniform and nonuniform attenuation correction to be in the range of 6.4%-16.0% for brain regions of interest (ROIs). The human control subjects who received transmission scans only were used to generate a curvilinear function to convert 57Co attenuation values into those for 123I, based on a pixel-by-pixel comparison of two coregistered transmission images for each subject. These values were applied to the group of patients and healthy control subjects who received transmission 57Co scans and emission 123I scans after injection of 123I-beta-CIT. In comparison to nonuniform attenuation correction as the gold standard, uniform attenuation with the ellipse drawn around the transmission image caused an approximately 5% error, whereas placement of the ellipse around the emission image caused a 15% error. Nonuniform attenuation correction allowed a moderate improvement in the measurement of absolute activity in individual brain ROIs. When images were analyzed as target-to-background activity ratios, as is commonly performed with 123I-beta-CIT, these outcome measures showed only small differences when Parkinson's disease patients and healthy control subjects were compared using nonuniform, uniform or even no attenuation correction.

Changes in regional cerebral glucose metabolism were investigated for varying levels of tissue oxygenation using a dynamic positron autoradiography technique. While incubating fresh rat brain slices with[18F]FDG in an oxygenated solution, serial images of the tissue slices were obtained over a time period of up to 300 min and archived onto over 20 phosphorous imaging plate exposures. In order to properly create time activity curves of the uptake levels, images of the individual tissue samples were automatically located, digitally extracted, and registered with the later images of the same tissue samples. After applying image processing techniques for aligning tissue sample images, time activity curves were extracted for individual substructures in the rat brain and quantitative results were reported using Patlak plots. Since the levels of oxygenation can be controlled for these experiments, [18F]FDG uptakes can be reported representing states of hypoxia, pseudoischemia, and reoxygenation. The image processing techniques developed for this application have enabled more experiments and tissue samples to be acquired and analyzed than would otherwise be possible using manual ROI techniques. The objective spatial registration of tissue samples and automated extraction of data has increased the analysis accuracy and decreased the operator error associated with the interactive handling of the image data. This supports improved kinetic modeling of FDG uptake in animal studies, and can be used for more accurate dosimetry calculations in humans.

Volumes-of-interest (VOIs) were drawn on an average image from the first SPECT scan day, and VOIs included whole brain, cerebellum, brainstem, thalamus, and frontal, temporal, parietal and occipital cortex.