Search

The aim of this study was to compare the diagnostic performance of the rabbit visual pattern versus the one endorsed by the EANM/SNMMI for the diagnosis of parkinsonian syndromes in PET/MRI.The 18F-DOPA PET images of 129 consecutive patients (65 Park+ and 64 controls) with 1 year of clinical follow-up were reviewed independently by 5 experienced readers on the same imaging workstation, blinded to the final clinical diagnosis. Two visual methods were assessed independently, with several days to months of interval: the criteria endorsed by EANM/SNMMI and the "rabbit" shape of the striate assessed on 3D MIP images. The sensitivities, specificities, likelihood ratios, and predictive values of the 2 diagnostic tests were estimated simultaneously by using the "comparison of 2 binary diagnostic tests to a paired design" method.The estimated 95% confidence interval (CI) of sensitivities and specificities ranged from 49.4% to 76.5% and from 83.2% to 97.7%, respectively. The 95% CI estimates of positive and negative likelihood ratios ranged from 3.8 to 26.7 and from 0.26 to 0.56, respectively. The 95% CI estimates of the positive and negative predictive values ranged from 78.1% to 96.7% and from 60.3% to 81.4%, respectively. For all the parameters, no statistical difference was observed between the 2 methods (P0.05). The rabbit sign reduced the readers' discrepancies by 25%, while maintaining the same performance.The rabbit visual pattern appears at least comparable to the current EANM/SNMMI reference procedure for the assessment of parkinsonian syndromes in daily clinical practice, without the need of any image postprocessing. Further multicenter prospective studies would be of relevance to validate these findings.

Purpose: Hybrid PET/MR is a promising tool in focal drug-resistant epilepsy, however the additional value for the detection of epileptogenic lesions and surgical decision-making remains to be established.Methods: We retrospectively compared 18F-FDG PET/MR images with those obtained by a previous 18F-FDG PET co-registered with MRI (PET+MR) in 25 consecutive patients (16 females, 13-60 year-old) investigated for focal drug-resistant epilepsy. Visual analysis was performed by two readers blinded from imaging modalities, asked to assess the technical characteristics (co-registration, quality of images), confidence in results, location of PET abnormalities and presence of a structural lesion on MRI. The clinical impact on surgical strategy and outcome was assessed independently.Results: The location of epilepsy was temporal in 9 patients and extra-temporal in 16 others. MRI was initially considered negative in 21 of them. PET alone demonstrated metabolic abnormalities in 19 cases (76%), and the co-registration with MRI allowed the detection of 4 additional structural lesions. PET/MR was considered better performing than PET+MR in 56% of patients. The increase in sensitivity was 13% and new structural lesions (mainly focal cortical dysplasias) were detected in 6 patients (24%). Change of surgical decision-making was substantial for 40% of patients, consisting in avoiding invasive monitoring in 6 patients and modifying the planning in 4 others. Seizure-free outcome was obtained in 13/14 patients who underwent a cortical resection.Conclusion: Hybrid PET/MR improves the detection of epileptogenic lesions, allowing to optimize the presurgical work-up and to increase the proportion of successful surgery even in the more complex cases.

International audience; The complex structure of the skull bone, reflected in particular by spatial variations in thickness and density, leads to a heterogeneity of its acoustic properties. This results in a strong attenuation as well as specific phase shifts of the ultrasonic wave during its crossing, leading to a defocusing of the beam. The improvement of the quality of brain ultrasonography requires knowledge of these acoustic heterogeneities to shape the ultrasonic wavefront during the focusing and imaging processes. CT scan realized on a phantom of a human skull associated to a fusion tool available on an ultrafast ultrasound device (Aixplorer, Supersonic Imagine, France) allows the positioning of the phased array in real-time in the CT volume. Then, for a fixed position of the probe, the real geometry of the skull region insonified by the array can be used as input data of the simulation based imaging algorithms. In particular, the Plane Wave Imaging (PWI) and Total Focusing Method (TFM) algorithms exploit a direct model of beam propagation through 3-D complex surfaces in order to simulate and correct the aberrations due to the skull crossing. We illustrate the potential of this technique on several examples of brain echography.

In brain PET/MR applications, accurate attenuation maps are required for accurate PET image quantification. An implemented attenuation correction (AC) method for brain imaging is the single-atlas approach that estimates an AC map from an averaged CT template. As an alternative, we propose to use a zero echo time (ZTE) pulse sequence to segment bone, air and soft tissue. A linear relationship between histogram normalized ZTE intensity and measured CT density in Hounsfield units ([Formula: see text]) in bone has been established thanks to a CT-MR database of 16 patients. Continuous AC maps were computed based on the segmented ZTE by setting a fixed linear attenuation coefficient (LAC) to air and soft tissue and by using the linear relationship to generate continuous μ values for the bone. Additionally, for the purpose of comparison, four other AC maps were generated: a ZTE derived AC map with a fixed LAC for the bone, an AC map based on the single-atlas approach as provided by the PET/MR manufacturer, a soft-tissue only AC map and, finally, the CT derived attenuation map used as the gold standard (CTAC). All these AC maps were used with different levels of smoothing for PET image reconstruction with and without time-of-flight (TOF). The subject-specific AC map generated by combining ZTE-based segmentation and linear scaling of the normalized ZTE signal into [Formula: see text] was found to be a good substitute for the measured CTAC map in brain PET/MR when used with a Gaussian smoothing kernel of [Formula: see text] corresponding to the PET scanner intrinsic resolution. As expected TOF reduces AC error regardless of the AC method. The continuous ZTE-AC performed better than the other alternative MR derived AC methods, reducing the quantification error between the MRAC corrected PET image and the reference CTAC corrected PET image.

18F-DPA-714 is a second-generation tracer for PET imaging of the 18-kDa translocator protein (TSPO), a marker of neuroinflammation. Analysis and interpretation of TSPO PET are challenging, especially because of the basal expression of TSPO. The aim of this study was to evaluate a compartmental model that accounts for the effect of endothelial TSPO binding on the quantification of 18F-DPA-714 PET scans from a cohort of healthy subjects. Methods: Fifteen healthy subjects (9 high-affinity binders and 6 mixed-affinity binders) underwent 18F-DPA-714 PET scans with arterial blood sampling and metabolite analysis. The kinetic parameters were quantified using a 2-tissue compartmental model (2TC) as well as a 2TC with an extra, irreversible, compartment for endothelial binding (2TC-1K). These regional parameters and messenger RNA (mRNA) expression specific to endothelial cells were correlated with regional TSPO mRNA expression. Results: The 2TC-1K model was more appropriate than the 2TC for 81% of fits. The total volume of distribution was significantly reduced by 21% ± 12% across all regions with the 2TC-1K, compared with the 2TC. The endothelial binding parameter Kb varied highly across brain regions. Kb strongly and significantly correlated with all 3 probes extracted for TSPO mRNA expression (r = 0.80, r = 0.79, and r = 0.90), but no correlation was seen with the other binding parameters from the 2TC-1K. For the 2TC, there was a lower but significant correlation between the volume of distribution and one of the TSPO mRNA probes (r = 0.65). A strong, significant correlation was seen between mRNA for TSPO and genes specific to endothelial cells. Conclusion: Accounting for endothelial TSPO in the kinetic model improved the fit of PET data. The high correlation between Kb and TSPO mRNA suggests that the 2TC-1K model reveals more biologic information about the regional density of TSPO than the 2TC. The correlation between TSPO and endothelial cell mRNA supports the relationship between the regional variation of Kb and endothelial TSPO. These results can improve the estimation of binding parameter estimates from 18F-DPA-714 PET, especially in diseases that induce vascular change.

One of the challenges of PET/MR is replacing CT-measured attenuation map with a MR-based, especially in the absence of bone signal in MR images. Regular MRI cannot distinguish between different tissue types based on electron density, thus, Zero Echo Time (ZTE) has been used to segment bone, air and soft tissue. In this study, we have evaluated the relationship between bone density measured in CT and signal intensity measured in ZTE on an CT-MR database of 16 patients. A linear relationship has been found on bone voxels between normalized ZTE intensity and CT density in Hounsfield Unit (HU). Using this relationship, we can derive patient-specific pseudo-CT from ZTE images.

The prevalence of neurodegenerative diseases is growing in western countries and PET imaging is increasingly frequently used for clinical and research purposes. However, few PET cameras are dedicated to cerebral imaging. The Biograph 6 (Biograph6) (Siemens Medical Solutions) is a PET/CT dedicated to high throughput whole body studies. Its performance for cerebral imaging has not yet been assessed. The aims of this study were to compare the quantification and detectability of the Biograph for cerebral imaging with those of a well-validated PET camera, the ECAT EXACT HR+ (HR+) (Siemens Medical Solutions). A phantom measuring 19 cm long and 20 cm in diameter was filled with a 18F-fluorodeoxyglucose (18F-FDG) solution. Two 5.7 and 20 ml spheres filled with water (cold-spots), three 0.25 ml spheres (sphere-to-background: 3, 6, and 12), one 1.14 ml sphere (sphere-to-background: 3), and one 11.27 ml sphere (sphere-to-background: 2) filled with a radioactive solution were inserted into the phantom. The activity concentration was chosen so that the count rates for the phantom measurements matched those of typical brain studies on both cameras. Images were reconstructed using FORE and OSEM algorithms. The reconstruction parameters were adjusted to obtain a similar signal-to-noise ratio in images acquired with the two cameras. The contrast recovery (CR) coefficients were similar on the two scanners for the 5.7 and 20 ml spheres (cold spheres) and the 1.14 and 11.27 ml spheres (hot spheres). For the 0.25 ml spheres, the CR values were 35% higher for the sphere-to-background ratio of 12 and 39% higher for the sphere-to-background ratio of 6 on the Biograph6 for the 3 min scan. The variability of measurements was lower on the Biograph6 than on the HR+. The detectability for the smallest spheres on the Biograph6 was close to that on the HR+. The Biograph has similar performances as the HR+ reference tomograph for the detection and quantification of small hot spots and cold spots.

In any domain, simulations are of utmost importance for assessing and predicting the performance of post-processing methods by controlling the truth and all model's parameters. In PET, two simulation methods exist: analytical and Monte Carlo. While not being as realistic as Monte Carlo ones, analytical simulations are fast enough for generating statistical replicates and realistic enough for assessing data-processing methods, especially in regard with noise. In this work, our aim was to produce replicated simulations of dynamic PET brain scans with realistic count rates properties. We extended the methodology of the analytical simulator ASIM [1] to get (i) a different modeling of the partial volume effect (down-sampling and image-based PSF modeling), (ii) a projection model based on real crystal coordinates, (iii) a fan-sum based random distribution and (iv) an intrinsic modeling of the decay and count rates through the dynamic acquisition. Attenuation, normalization (from real crystal efficiencies), scatters (convolution-based) and randoms (fan-sum based) were taken into account. The Zubal brain phantom and the geometry of the Siemens Biograph Hirez 4-rings scanner were used. All other input parameters were extracted from real acquisitions of volunteers with the HRRT: frame durations, time-activity curves, scatter and random fractions and total number of prompts for the whole acquisition. Simulated count rates were compared to those from the acquisitions on a frame-by-frame basis, for three different tracers. Results showed good agreements and realistic reconstructed images. These data will be used for assessing reconstruction and post-processing methods in the context of dynamic PET brain scans.

Longitudinal positron emission tomography (PET) studies of 6-18F-L-dopa uptake in the striatum are used to assess the progression of Parkinson's disease or the survival of neuronal cells grafted in parkinsonian patients. These studies are performed over several years, and data analysis may suffer from the change from old tomographs to new machines with better sensitivity and spatial resolution. Furthermore, such studies on parkinsonian patients may be accomplished in either 2D or 3D acquisition mode. The aforementioned improvements offer great benefits for the study of neurodegenerative diseases, especially those affecting the striatum. However, direct comparison of data is not straightforward owing to variation in scanner characteristics. In this study, we assessed the feasibility of comparing the 6-18F-L-dopa striatal uptake values (Kc) measured in two groups of healthy subjects using two tomographs of different generations. We re-studied and compared acquisitions performed on 14 healthy subjects using 6-18F-L-dopa. Half of these studies had been performed in 2D acquisition mode using an ECAT 953B. The other half had been performed in 3D acquisition mode using an ECAT EXACT HR+. Different reconstruction protocols were used and the Kc values obtained were statistically compared. The results showed that lowering the transverse spatial resolution of images obtained with the scanner having the better spatial resolution, so that it more closely matched that of the other machine, allowed similar KC values to be obtained in healthy subjects. This study shows that quantitative results of 6-18F-L-dopa scans can be matched between different scanners with different intrinsic resolutions. This can be accomplished using adequate modifications of the reconstruction parameters. Such modifications can be used to help in the longitudinal monitoring of parkinsonian patients using different tomographs.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Activated microglia/macrophages play a key role in the immunopathogenesis of MS and its corresponding animal models, experimental autoimmune encephalomyelitis (EAE). Microglia activation begins at early stages of the disease and is associated with elevated expression of the 18 kDa mitochondrial translocator protein (TSPO). Thus, positron emission tomography (PET) imaging of microglial activation using TSPO-specific radioligands could be valuable for monitoring disease-associated neuroinflammatory processes. EAE was induced in rats using a fragment of myelin basic protein, yielding acute clinical disease that reflects extensive spinal cord inflammation. Enhanced TSPO expression in spinal cords of EAE rats versus those of controls was confirmed by Western blot and immunohistochemistry. Biodistribution studies in control and EAE rats were performed using the TSPO radioligand [18F]DPA-714 [N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide]. At 1 h after injection, almost fivefold higher levels of [18F]DPA-714 were measured in spinal cords of EAE rats versus controls. The specific binding of [18F]DPA-714 to TSPO in spinal cords was confirmed in competition studies, using unlabeled (R,S)-PK11195 [(R,S)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide)] or DPA-714 in excess. MicroPET studies affirm that this differential radioactivity uptake in spinal cords of EAE versus control rats could be detected and quantified. Using [18F]DPA-714, neuroinflammation in spinal cords of EAE-induced rats could be visualized by PET, offering a sensitive technique for monitoring neuroinflammatory lesions in the CNS and particularly in the spinal cord. In addition to current MRI protocols, this approach could provide molecular images of neuroinflammation for detection, monitoring, and research in MS.

State of the art positron emission tomography (PET) systems allow for scatter and attenuation correction. However, the size of the structure being studied and the region of interest (ROI) chosen also influence the accuracy of measurements of radioactive concentration. Furthermore, the limited spatial resolution of PET tomographs, which depends, among other factors, on the range of positrons in matter, can also contribute to a loss in quantitation accuracy. In this paper we address the influence of positron range, structure size and ROI size on the quantitation of radioactive concentration using PET. ECAT EXACT HR+ (HR+) and ECAT 953B/31 (ECAT 953B) PET systems were used in phantom acquisitions performed with two radioisotopes with different positron ranges. The 3D Hoffman phantom was scanned on both scanners with both radioisotopes, to visually analyse the image quality. A resolution phantom having six spheres of different diameters in a Plexiglas cylinder was used to calculate the values of the contrast recovery coefficient or hot spot recovery coefficient and of the spill-over or cold spot recovery coefficient under different imaging conditions used in clinical routine at our institution. Activity ratios were varied between 2 and 30 or between 0.4 and 200 by filling the spheres with fluorine-18 or bromine-76 respectively and the cylinder with 11C. Dynamic scans were performed on each scanner. Data were reconstructed using the same parameters as are used in clinical protocols. The variations in sphere and cylinder activities with time were fitted using the function M(t)=k1·A(t)+k2.B(t), where M(t) is the radioactivity concentration measured in an ROI placed on each sphere and A(t) and B(t) represent the true radioactivity concentrations present at time t in the spheres and in the cylinder respectively. k1 and k2 are factors representing the contrast recovery coefficient and the spill-over from surrounding activity on measurements respectively. The visual analysis of images obtained using a 3D Hoffman phantom showed that image resolution and image contrast between different regions are radioisotope dependent and clearly better when using 18F. Linear profiles taken on these images confirmed the visual assessment. For a given scanner, the k1 values obtained with 18F were systematically higher than those measured using 76Br in the same machine (especially for the smaller spheres) when using the same ROI. For a sphere of a particular diameter, the use of a wider ROI resulted in lower quantitative accuracy when using the same isotope and the same camera. Lower quantitative accuracy was found for smaller spheres for all ROI sizes used in image analysis. For the same scanner and for a similar imaging situation (same sphere and same ROI), it was found that k1 and k2 values depend on the radioisotope used. For the same isotope and tomograph, the k1 values obtained decreased with the size of the structures imaged, as well as with the increase in ROI size. The use of a tomograph with better spatial resolution (HR+, rather than ECAT 953B) greatly increased the k1 values for 18F while only a mild improvement in these values was observed for 76Br. The use of 76Br led to k2 values that were slightly higher than those measured using 18F. These differences may have been due to the difference in the range of the positrons emitted by the radioisotopes used in this study. The measurements performed in this study show that the comparison of studies obtained on the same camera depends on the radioisotope used and may require the adaptation of ROI size between examinations. Marked differences are visible if the positron ranges of such radioisotopes are very different. Therefore, when employing commercially available tomographs and imaging protocols used in clinical routine, the effects of differences in positron range on image quality and quantitation are noticeable and correction for these effects may be of importance. With the arrival of PET imaging systems with better spatial resolution (close to 2 mm full-width at half-maximum for animal PET systems), positron range will have an increasing influence on the image quality and on the choice of radioisotope for a given application.

We present the results from various phantom measurements conducted on the ECAT 953B at Orsay. In particular we emphasize the potentials for quantitation and examine the effects of scatter and limited resolution.

We implemented a hybrid scatter-correction method for 3D PET that combines two scatter-correction methods in a complementary way. The implemented scheme uses a method based on the discrimination of the energy of events (the estimation of trues method (ETM)) and an auxiliary method (the single scatter simulation method (SSS1) or the convolution–subtraction method (CONV)) in an attempt to increase the accuracy of the correction over a wider range of acquisitions. The ETM takes into account the scatter from outside the field-of-view (FOV), which is not estimated with the auxiliary method. On the other hand, the auxiliary method accounts for events that have scattered with small angles, which have an energy that cannot be discriminated from that of unscattered events using the ETM. The ETM uses the data acquired in an upper energy window above the photopeak (550–650 keV) to obtain a noisy estimate of the unscattered events in the standard window (350–650 keV). Our implementation uses the auxiliary method to correct the residual scatter in the upper window. After appropriate scaling, the upper window data are subtracted from the total coincidences acquired in the standard window, resulting in the final scatter estimate, after smoothing. In this work we compare the hybrid method with the corrections used by default in the 2D and 3D modes of the ECAT EXACT HR+ using phantom measurements. Generally, the contrast was better with the hybrid method, although the relative errors of quantification were similar. We conclude that hybrid techniques such as the one implemented in this work can provide an accurate, general-purpose and practical way to correct the scatter in 3D PET, taking into account the scatter from outside the FOV.