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PurposeLoss of brain synapses is an early pathological feature of Alzheimer’s disease. The current study assessed synaptic loss in vivo with positron emission tomography and an 18F-labelled radiotracer of the synaptic vesicle protein 2A, [18F]UCB-H.MethodsTwenty-four patients with mild cognitive impairment or Alzheimer’s disease and positive [18F]Flutemetamol amyloid-PET were compared to 19 healthy controls. [18F]UCB-H brain uptake was quantified with Logan graphical analysis using an image-derived blood input function. SPM12 and regions-of-interest (ROI) analyses were used for group comparisons of regional brain distribution volumes and for correlation with cognitive measures.ResultsA significant decrease of [18F]UCB-H uptake was observed in several cortical areas (11 to 18% difference) and in the thalamus (16% difference), with the largest effect size in the hippocampus (31% difference). Reduced hippocampal uptake was related to patients’ cognitive decline (ROI analysis) and unawareness of memory problems (SPM and ROI analyses).ConclusionsThe findings thus highlight predominant synaptic loss in the hippocampus, confirming previous autopsy-based studies and a recent PET study with an 11C-labelled SV2A radiotracer. [18F]UCB-H PET allows to image in vivo synaptic changes in Alzheimer’s disease and to relate them to patients’ cognitive impairment.

The purpose of this exploratory research is to provide data on synaptopathy in the behavioral variant of frontotemporal dementia (bvFTD). Twelve patients with probable bvFTD were compared to 12 control participants and 12 patients with Alzheimer’s disease (AD). Loss of synaptic projections was assessed with [ 18 F]UCBH-PET. Total distribution volume was obtained with Logan method using carotid artery derived input function. Neuroimages were analyzed with SPM12. Verbal fluency, episodic memory and awareness of cognitive impairment were equally impaired in patients groups. Compared to controls, [ 18 F]UCBH uptake tended to decrease in the right anterior parahippocampal gyrus of bvFTD patients. Loss of synaptic projections was observed in the right hippocampus of AD participants, but there was no significant difference in [ 18 F]UCBH brain uptake between patients groups. Anosognosia for clinical disorder was correlated with synaptic density in the caudate nucleus and the anteromedial prefrontal cortex. This study suggests that synaptopathy in bvFTD targets the temporal social brain and self-referential processes.

Background This study aimed to analyse the quantitative capabilities of cadmium-zinc-telluride (CZT)-based SPECT-CT cameras using 99m Tc, comparable to the analysis performed a decade ago for the sodium iodide (NaI) SPECT-CT systems available on the market at that time. This survey assessed one dual-head (GE Discovery NM870 CZT) and two ring (GE Starguide, Spectrum Dynamics Veriton 200) CZT cameras, as well as a state-of-the-art NaI dual-head system (Siemens Intevo Bold) that served as reference. Attenuation and scatter correction accuracy was explored, contrast recovery for small cold and hot rods measured, as well as the quantification in a large uniform area using user-determined conversion factors. Tomography reconstruction was performed with the manufacturers’ iterative algorithms that allowed for attenuation correction, scatter correction and resolution recovery. Results Using the NEMA NU-2 1994 dedicated phantom, attenuation and scatter corrections seemed to perform very well. Equally, the contrast recovery of cold rods seemed to be superior for the CZT systems. However, the contrast recovery for the hot rods was inferior to the NaI camera, whereas it was comparable without the scatter correction. Finally, a quantification error of less than 5% was shown to be reachable when using adequate user-determined conversion factors. For the NaI camera, all results were similar to those of the past study. Conclusions Without scatter correction, the CZT SPECT systems showed contrast performance similar to the NaI camera. With scatter correction, this held true for cold objects but the contrast of hot objects was not significantly improved or was degraded depending on the system considered and the object size. Quantification errors of less than 5% were achievable. It is hoped that on-going developments at both manufacturers will improve the scatter correction accuracy.

Background This study investigated, mainly for quantitative 99m Tc explorations with a ring CZT SPECT system (GE HealthCare Starguide), the use of a narrow symmetric or a fully asymmetric energy window to reject scattered photons. The results were compared with the manufacturer’s post-acquisition dual energy window approach. Methods Two uniform and two cold and hot rod contrast cylindrical phantoms of various sizes were scanned with the Starguide system to acquire a very high number of counts. After rebinning the list-mode files for different energy windows, data were reconstructed with manufacturer’s iterative algorithm including attenuation correction, resolution recovery and eventually scatter correction, but without any regularization technique. Cold rod residual scatter fraction, hot and cold rod contrast recovery coefficient, coefficient of variation in phantom uniform areas and quantification accuracy using calibration with one of the homogeneous phantoms were, among others, computed. Results Narrow symmetric photopeak-centred windows or fully asymmetric (≥ 140 keV) window led, on one hand, to decreased scatter residual fraction and sensitivity and, on the other hand, to increased noise, cold and hot recovery coefficients when compared to a standard 15–20% wide symmetric window. With a 6–7% wide symmetric window we obtained very comparable results to the dual energy window scatter correction used by the manufacturer for all measured parameters, but larger recovery coefficients especially for small hot objects in a cold background. Similar results were obtained with the fully asymmetric window at the cost of a higher noise level resulting from a drastic reduction of the sensitivity. Conclusions Narrow symmetric or asymmetric energy windows were found an interesting alternative to the standard dual energy window method to reject 99m Tc scattered photons. As a key feature, they allowed to avoid the erasing of small hot objects in a null background that was observed with the standard dual energy window scatter correction.

Purpose Our objective was to assess a deconvolution and denoising technique based on Legendre polynomials compared to matrix deconvolution on dynamic 18 F-FDG renography of healthy patients. Method The study was carried out and compared to the data of 24 healthy patients from a published study who underwent examinations with 99m Tc-MAG3 planar scintigraphy and 18 F-FDG PET/MRI. Due to corruption issues in some data used in the published article, post-publication measurements were provided. We have been warned that post-publication data were treated differently. The smoothing method switched from Bezier to Savitzky–Golay and the deconvolution from matrix-based (with Tikhonov Regularization) to Richardson–Lucy. A comparison of the split function and mean transit times of the published and post-publication data against our method based on Legendre polynomials was performed. Results For split function, we only observed a good agreement between the processing methods for the 99m Tc-MAG 3 and the post-published data. No correlation was found between the split functions obtained on the 99m Tc-MAG 3 and the 18 F-FDG, contrary to the published study. However, all calculated split function values for 18 F-FDG and 99m Tc-MAG 3 were within the established normal range. For the mean transit time, the correlation was moderate with published data and very good with the post-publication measurements for both 99m Tc-MAG 3 and 18 F-FDG. Bias of the Bland–Altman analysis of the mean transit times for 99m Tc-MAG 3 versus 18 F-FDG was 1.1 min (SD 1.7 min) for the published data, − 0.11 min (SD 1.9 min) for the post-publication results and .05 min (SD 1.9 min) for our method. Conclusions The processing methods used in the original publication and in the post-publication work were quite complex and required adaptation of the fitting parameters for each individual and each type of examination. Our method did not require any specific adjustment; the same unmodified and fully automated algorithm was successfully applied to all data.

The synaptic vesicle protein 2 (SV2) is involved in synaptic vesicle trafficking. The SV2A isoform is the most studied and its implication in epilepsy therapy led to the development of the first SV2A PET radiotracer [18F]UCB-H. The objective of this study was to evaluate in vivo, using microPET in rats, the specificity of [18F]UCB-H for SV2 isoform A in comparison with the other two isoforms (B and C) through a blocking assay. Twenty Sprague Dawley rats were pre-treated either with the vehicle, or with specific competitors against SV2A (levetiracetam), SV2B (UCB5203) and SV2C (UCB0949). The distribution volume (Vt, Logan plot, t* 15 min) was obtained with a population-based input function. The Vt analysis for the entire brain showed statistically significant differences between the levetiracetam group and the other groups (p < 0.001), but also between the vehicle and the SV2B group (p < 0.05). An in-depth Vt analysis conducted for eight relevant brain structures confirmed the statistically significant differences between the levetiracetam group and the other groups (p < 0.001) and highlighted the superior and the inferior colliculi along with the cortex as regions also displaying statistically significant differences between the vehicle and SV2B groups (p < 0.05). These results emphasize the in vivo specificity of [18F]UCB-H for SV2A against SV2B and SV2C, confirming that [18F]UCB-H is a suitable radiotracer for in vivo imaging of the SV2A proteins with PET.

This study investigated, mainly for quantitative Tc explorations with a ring CZT SPECT system (GE HealthCare Starguide), the use of a narrow symmetric or a fully asymmetric energy window to reject scattered photons. The results were compared with the manufacturer's post-acquisition dual energy window approach. Two uniform and two cold and hot rod contrast cylindrical phantoms of various sizes were scanned with the Starguide system to acquire a very high number of counts. After rebinning the list-mode files for different energy windows, data were reconstructed with manufacturer's iterative algorithm including attenuation correction, resolution recovery and eventually scatter correction, but without any regularization technique. Cold rod residual scatter fraction, hot and cold rod contrast recovery coefficient, coefficient of variation in phantom uniform areas and quantification accuracy using calibration with one of the homogeneous phantoms were, among others, computed. Narrow symmetric photopeak-centred windows or fully asymmetric (≥ 140 keV) window led, on one hand, to decreased scatter residual fraction and sensitivity and, on the other hand, to increased noise, cold and hot recovery coefficients when compared to a standard 15-20% wide symmetric window. With a 6-7% wide symmetric window we obtained very comparable results to the dual energy window scatter correction used by the manufacturer for all measured parameters, but larger recovery coefficients especially for small hot objects in a cold background. Similar results were obtained with the fully asymmetric window at the cost of a higher noise level resulting from a drastic reduction of the sensitivity. Narrow symmetric or asymmetric energy windows were found an interesting alternative to the standard dual energy window method to reject Tc scattered photons. As a key feature, they allowed to avoid the erasing of small hot objects in a null background that was observed with the standard dual energy window scatter correction.

This study aimed to analyse the quantitative capabilities of cadmium-zinc-telluride (CZT)-based SPECT-CT cameras using Tc, comparable to the analysis performed a decade ago for the sodium iodide (NaI) SPECT-CT systems available on the market at that time. This survey assessed one dual-head (GE Discovery NM870 CZT) and two ring (GE Starguide, Spectrum Dynamics Veriton 200) CZT cameras, as well as a state-of-the-art NaI dual-head system (Siemens Intevo Bold) that served as reference. Attenuation and scatter correction accuracy was explored, contrast recovery for small cold and hot rods measured, as well as the quantification in a large uniform area using user-determined conversion factors. Tomography reconstruction was performed with the manufacturers' iterative algorithms that allowed for attenuation correction, scatter correction and resolution recovery. Using the NEMA NU-2 1994 dedicated phantom, attenuation and scatter corrections seemed to perform very well. Equally, the contrast recovery of cold rods seemed to be superior for the CZT systems. However, the contrast recovery for the hot rods was inferior to the NaI camera, whereas it was comparable without the scatter correction. Finally, a quantification error of less than 5% was shown to be reachable when using adequate user-determined conversion factors. For the NaI camera, all results were similar to those of the past study. Without scatter correction, the CZT SPECT systems showed contrast performance similar to the NaI camera. With scatter correction, this held true for cold objects but the contrast of hot objects was not significantly improved or was degraded depending on the system considered and the object size. Quantification errors of less than 5% were achievable. It is hoped that on-going developments at both manufacturers will improve the scatter correction accuracy.

Our objective was to assess a deconvolution and denoising technique based on Legendre polynomials compared to matrix deconvolution on dynamic F-FDG renography of healthy patients. The study was carried out and compared to the data of 24 healthy patients from a published study who underwent examinations with Tc-MAG3 planar scintigraphy and F-FDG PET/MRI. Due to corruption issues in some data used in the published article, post-publication measurements were provided. We have been warned that post-publication data were treated differently. The smoothing method switched from Bezier to Savitzky-Golay and the deconvolution from matrix-based (with Tikhonov Regularization) to Richardson-Lucy. A comparison of the split function and mean transit times of the published and post-publication data against our method based on Legendre polynomials was performed. For split function, we only observed a good agreement between the processing methods for the Tc-MAG and the post-published data. No correlation was found between the split functions obtained on the Tc-MAG and the F-FDG, contrary to the published study. However, all calculated split function values for F-FDG and Tc-MAG were within the established normal range. For the mean transit time, the correlation was moderate with published data and very good with the post-publication measurements for both Tc-MAG and F-FDG. Bias of the Bland-Altman analysis of the mean transit times for Tc-MAG versus F-FDG was 1.1 min (SD 1.7 min) for the published data, - 0.11 min (SD 1.9 min) for the post-publication results and .05 min (SD 1.9 min) for our method. The processing methods used in the original publication and in the post-publication work were quite complex and required adaptation of the fitting parameters for each individual and each type of examination. Our method did not require any specific adjustment; the same unmodified and fully automated algorithm was successfully applied to all data.

This work aimed to evaluate the image quality and accuracy of attenuation and scatter corrections provided with the microPET Focus 120 scanner using the National Electrical Manufacturers Association NU4-2008 image quality phantom. Attenuation correction was obtained from transmission measurements using either a (68)Ge or a (57)Co point source. Fully corrected emission images were reconstructed using Fourier rebinning (FORE) and filtered backprojection (FBP). For attenuation data obtained with the (57)Co source, fully corrected emission images were also reconstructed using FORE and 2-dimensional (2D) ordered-subset expectation maximization (OSEM), 3-dimensional (3D) filtered backprojection (3DRP), 3D OSEM, and 3D maximum a posteriori methods. The mean activity, the coefficients of variation (COVs) of the uniform slices, the recovery coefficients (RCs) for hot rods, and the spillover ratio (SOR) for nonemitting water and air compartments were measured. For (57)Co-based attenuation correction, the mean activity value differed by less than 3% from the true activity. Measuring the attenuation with (68)Ge resulted in lower reconstructed activity and higher COV. On the basis of (57)Co measurements, the SORs for air and water nonemitting compartments were the closest to zero for attenuation correction. The RC measured on emission images corrected for attenuation but not for scatter did not show any significant difference linked to the transmission method. However, higher RCs were noted for transmission measurement with (68)Ge in coincidence with windowing when emission data were corrected for attenuation and scatter. This resulted from a lower mean value in the uniform area. 2D and 3DRP reconstruction methods showed little effect on the mean activity value, whereas iterative 3D methods gave 7% higher values. Higher RCs were found with iterative reconstruction than with FBP and 3DRP. However, the SOR seemed to be optimal with FBP. SORs were higher with iterative methods and decreased with the number of iterations. For studies of small rodents with the Focus 120, (57)Co transmission seems to be the most suitable method for attenuation correction. FORE and 2D reconstruction methods appear to be a good compromise between overall image quality and reconstruction time: OSEM provides the largest contrasts, but FBP provides superior attenuation and scatter correction.