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Cholinergic alterations in dementia with Lewy bodies (DLB) have been widely documented in postmortem studies, whereas in vivo studies are sparse, particularly at the subcortical level. We used 123 I-iodobenzovesamicol, a SPECT radiotracer of the vesicular acetylcholine transporter, to evaluate in vivo in DLB the integrity of the 3 main cholinergic pathways-the Ch1 (septohippocampal), the Ch4 (innominatocortical), and the Ch5 (pontothalamic) cholinergic pathways-as well as the striatal cholinergic interneurons. In addition, we assessed the involvement of the cholinergic system in cognitive and neuropsychiatric disorders in DLB patients., Methods: Twelve healthy volunteers (median age, 72 y; interquartile range, 6.25 y) and 11 DLB patients (median age, 76 y; interquartile range, 10.50 y) underwent a dynamic 123 I-iodobenzovesamicol SPECT scan and an MRI scan. MR images were automatically segmented, providing the volumes of several regions of interest, including the striatum and cholinergic terminals in Ch1 (hippocampus), Ch4 (cortical lobes), and Ch5 (thalamus). For each region of interest and each subject, pharmacokinetic modeling allowed calculation of the nondisplaceable binding potential (BP ND ) values for the binding of 123 I-iodobenzovesamicol to the vesicular acetylcholine transporter. A neuropsychological evaluation of participants was performed with the Mini-Mental State Examination and the Grober-Buschke, Set, visual discrimination, Benton, and Wechsler tests, and cognitive fluctuations and apathy were also assessed., Results: Compared with BP ND values for healthy subjects, BP ND values for DLB patients were significantly lower in the Ch4 terminal regions of the anterior cingulate cortex and the superior and inferior parietal cortices (P = 0.0006, 0.0015, and 0.0023, respectively), in the Ch5 terminal region of the thalamus (P = 0.0003), and in the striatum (P = 0.0042). All of the neuropsychological test scores were significantly lower in DLB patients than in healthy subjects. Four DLB patients with apathy and 4 DLB patients without apathy were identified. For the anterior cingulate cortex, compared with BP ND values in healthy subjects, BP ND values were significantly lower in patients with apathy (P = 0.004) and were unchanged in patients without apathy., Conclusion: Our results confirm the existence in DLB of cholinergic alterations, reaching both cortical and subcortical levels, including the Ch5 pathway and the striatum. Alterations in cholinergic transmission in the anterior cingulate cortex could be closely associated with the development of apathy., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Unlabelled: The performance of an average SUV over a 1-mL-volume sphere within an (18)F-FDG-positive lesion resulting in the highest possible value (SUVpeakW) was compared with that of an average SUV computed from the 40 hottest voxels, irrespective of their location within the lesion (SUVmax-40)., Methods: Dynamic PET performed in 20 lung cancer lesions yielded for each SUV metric its mean value, relative measurement error, and repeatability (MEr-R)., Results: SUVpeakW mean value was significantly 9.66% lower than that of SUVmax-40 (P < 0.0001). SUVpeakW and SUVmax-40 MEr-R were significantly lower than the MEr-R of SUVmax (the hottest voxel): 9.35%-13.21% and 8.84%-12.49% versus 13.86%-19.59%, respectively, (95% confidence limit; P < 0.0001). Although being marginal, SUVpeakW MEr-R was not significantly greater than SUVmax-40 MEr-R (P = 0.086)., Conclusion: SUVmax-40 is more likely to represent the most metabolically active portions of tumors than SUVpeakW, with close variability performance., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: (123)I-iodobenzovesamicol is a SPECT radioligand selective for the vesicular acetylcholine transporter (VAChT) and used to assess the integrity of cholinergic pathways in various neurologic disorders. The current noninvasive method for quantitative analysis of (123)I-iodobenzovesamicol, based on multilinear reference tissue model 2 (MRTM2), requires repeated scans for several hours, limiting its application in clinical trials. Our objective was to validate a simplified acquisition method based on a single (123)I-iodobenzovesamicol static scan preserving the quantification accuracy. Three acquisition times were tested comparatively to a kinetic analysis using MRTM2., Methods: Six healthy volunteers underwent a dynamic SPECT acquisition comprising 14 frames over 28 h and an MR imaging scan. MR images were automatically segmented, providing the volumes of 19 regions of interest (ROIs). SPECT datasets were coregistered with MR images, and regional time-activity curves were derived. For each ROI, a complete MRTM2 pharmacokinetic analysis, using the cerebellar hemispheres as the reference region, led to the calculation of a (123)I-iodobenzovesamicol-to-VAChT binding parameter, the nondisplaceable binding potential (BP(ND-MRTM2)). A simplified analysis was also performed at 5, 8, and 28 h after injection, providing a simplified BP(ND), given as BP(ND-t) = C(ROI) - C(cerebellar hemispheres)/C(cerebellar hemispheres), with C being the averaged radioactive concentration., Results: No significant difference was found among BP(ND-5 h), BP(ND-8 h), and BP(ND-MRTM2) in any of the extrastriatal regions explored. BP(ND-28 h) was significantly higher than BP(ND-5 h), BP(ND-8 h), and BP(ND-MRTM2) in 9 of the 17 regions explored (P < 0.05). BP(ND-5 h), BP(ND-8 h), and BP(ND-28 h) correlated significantly with BP(ND-MRTM2) (P < 0.05; ρ = 0.99, 0.98, and 0.92, respectively). In the striatum, BP(ND-28 h) was significantly higher than BP(ND-5 h) and BP(ND-8 h). BP(ND-5 h) differed significantly from BP(ND-MRTM2) (P < 0.05), with BP(ND-5 h) being 43.6% lower., Conclusion: In the extrastriatal regions, a single acquisition at 5 or 8 h after injection provides quantitative results similar to a pharmacokinetic analysis. However, with the highest correlation and accuracy, 5 h is the most suitable time to perform an accurate (123)I-iodobenzovesamicol quantification. In the striatum, none of the 3 times has led to an accurate quantification., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: Respiratory motion can potentially reduce accuracy in anatomic and functional image fusion from multimodality systems. It can blur the uptake of small lesions and lead to significant activity underestimation. Solutions presented to date include respiration-synchronized anatomic and functional acquisitions. To increase the signal-to-noise ratio of the synchronized PET images, methods using nonrigid transformations during the reconstruction process have been proposed. In most of these methods, 4-dimensional (4D) CT images were used to derive the required deformation matrices. However, variations between acquired 4D PET and corresponding CT image series due to differences in respiratory conditions during PET and CT acquisitions have been reported. In addition, the radiation dose burden resulting from a 4D CT acquisition may not be justifiable for every patient., Methods: In this paper, we present a method for the generation of dynamic CT images from the combination of one reference CT image and deformation matrices obtained from the elastic registration of 4D PET images not corrected for attenuation. On the one hand, our approach eliminates the need for the acquisition of dynamic CT. On the other hand, it also ensures a good match between CT and PET images, allowing accurate attenuation correction to be performed for respiration-synchronized PET acquisitions., Results: The proposed method was first validated on Monte Carlo-simulated datasets, and then on patient datasets (n = 4) by comparing generated 4D CT images with the corresponding acquired original CT images. Different levels of PET image statistical quality were considered in order to investigate the impact of image noise in the derivation of the 4D CT series., Conclusion: Our results suggest that clinically relevant PET acquisition times can be used for the implementation of such an approach, making this an even more attractive solution considering the absence of the extra dose given by a standard 4D CT acquisition. Finally, this approach may be applicable to other multimodality devices such as PET/MR.

Unlabelled: We investigated whether PET/CT angiography using 11C-(R)-PK11195, a selective ligand for the translocator protein (18 kDa) expressed in activated macrophages, could allow imaging and quantification of arterial wall inflammation in patients with large-vessel vasculitis., Methods: Seven patients with systemic inflammatory disorders (3 symptomatic patients with clinical suspicion of active vasculitis and 4 asymptomatic patients) underwent PET with 11C-(R)-PK11195 and CT angiography to colocalize arterial wall uptake of 11C-(R)-PK11195. Tissue regions of interest were defined in bone marrow, lung parenchyma, wall of the ascending aorta, aortic arch, and descending aorta. Blood-derived and image-derived input functions (IFs) were generated. A reversible 1-tissue compartment with 2 kinetic rate constants and a fractional blood volume term were used to fit the time-activity curves to calculate total volume of distribution (VT). The correlation between VT and standardized uptake values was assessed., Results: VT was significantly higher in symptomatic than in asymptomatic patients using both image-derived total plasma IF (0.55±0.15 vs. 0.27±0.12, P=0.009) and image-derived parent plasma IF (1.40±0.50 vs. 0.58±0.25, P=0.018). A good correlation was observed between VT and standardized uptake value (R=0.79; P=0.03)., Conclusion: 11C-(R)-PK11195 imaging allows visualization of macrophage infiltration in inflamed arterial walls. Tracer uptake can be quantified with image-derived IF without the need for metabolite corrections and evaluated semiquantitatively with standardized uptake values.