[en] Neuroimaging methods have considerably developed over the last decades and offer various noninvasive approaches for measuring cerebral metabolic fluxes connected to energy metabolism, including PET and magnetic resonance spectroscopy (MRS). Among these methods, ³¹P MRS has the particularity and advantage to directly measure cerebral ATP synthesis without injection of labeled precursor. However, this approach is methodologically challenging, and further validation studies are required to establish ³¹P MRS as a robust method to measure brain energy synthesis. In the present study, we performed a multimodal imaging study based on the combination of 3 neuroimaging techniques, which allowed us to obtain an integrated picture of brain energy metabolism and, at the same time, to validate the saturation transfer ³¹P MRS method as a quantitative measurement of brain ATP synthesis. A total of 29 imaging sessions were conducted to measure glucose consumption (CMRglc), TCA cycle flux (VTCA), and the rate of ATP synthesis (VATP) in primate monkeys by using ¹⁸F-FDG PET scan, indirect ¹³C MRS, and saturation transfer ³¹P MRS, respectively. These 3 complementary measurements were performed within the exact same area of the brain under identical physiological conditions, leading to: CMRglc = 0.27 ± 0.07 μmol.g^-1.min^-1, V_TCA = 0.63 ± 0.12 μmol.g^-1.min^-1, and V_ATP = 7.8 ± 2.3 μmol.g^-1.min^-1. The consistency of these 3 fluxes with literature and, more interestingly, one with each other, demonstrates the robustness of saturation transfer ³¹P MRS for directly evaluating ATP synthesis in the living brain. (authors)

[en] Neuroblastoma is the most common extracranial neoplasm in children. This disease has a great heterogeneity in his presentation and prognosis. ¹²³I-MIBG remains currently a key and reference exam for diagnosis, initial staging, prognosis and follow-up of neuroblastoma. SPECT/CT increased the diagnostic certainty of ¹²³I-MIBG scintigraphy interpretation and help to reduce false negative and false positive results. Bone scan is yet not indicated. ¹⁸FDG-PET/CT is not superior to ¹²³I-MIBG in stages 3 and 4. ¹⁸FDG-PET/CT is recommended in case of non-avid ¹²³I-MIBG neuroblastoma. ¹⁸F-FDOPA PET/CT could represent an alternative exam to ¹²³I-MIBG scintigraphy because of better spatial resolution and no interference with therapy. Other PET radiopharmaceuticals as ¹²⁴I-MIBG or ¹⁸F-MFBG could be interesting and particularly ⁶⁸Ga-peptides PET/ CT as a theranostic agent in providing valuable information for pretherapeutic staging of neuroblastoma. (authors)

[en] Complete text of publication follows: Aim/Introduction: besides the neurological diseases, others factors could influence the uptake of ¹⁸F-DOPA in the brain. Knowing their impact could ultimately lead to identify by quantitative measurements the neurological disorders. Therefore the impact of some of the most current physiological and pharmacological parameters has been evaluated in an almost normal population. Materials and Methods: 70 consecutive patients, referred for suspicion of Parkinson disease but by which the striatal F-DOPA uptake was normal on a PET/NMR examination, were included in the study. Age, gender, right- or left-handed, hypertension, diabetes and chronic intake of levodopa were retrospectively collected. For each patient, the SUV of 28 regions of interest of the trunk, the diencephalon and the cortex was measured from an automatic atlas based on the PET/NMR imaging. Briefly, the T1 images of each patient were registered on the T1 images of a reference model where several anatomical regions had been previously identified. The registration was carried out in a progressive way, in non-deformable and then deformable mode, after creation of a mask including the brainstem, the diencephalon and the striatum. The registration parameters were then applied to the ¹⁸F-DOPA images acquired 90 min after injection. The SUV of the 28 regions were finally related to the reticular SUV and the influence of the factors on them was statistically assessed by Student t-test. Results: influence of hypertension was the most prominent factor, increasing the ratio to reticular nuclei of the amygdala (+38%) and hypothalamus (+14%; p=0.009). The asymmetrical SUV of pulvinars decreased (-50%; p=0.004). Difference between SUV of substantia nigra and reticular nuclei increased (+36%; p=0.002). The chronic intake of levodopa reduced the amygdala to reticular ratio (19%; p=5.10-4). In male, the SUV ratio to reticular nuclei was higher in amygdala (+10%; p=0.01) and A8 region (+10%; p=0.005). Age, right-or left-handed and diabetes had no statistical influence in our population. Conclusion: Hypertension gender and the intake of levodopa are factors influencing the SUV to reticular ratio in different brain areas. These factors should be taken into consideration for quantitative discrimination between pathological and normal patients, chiefly for the analysis of the trunk, where the differences between pathology and normality are more subtle than in the striatum

[en] Complete text of publication follows: Aim/Introduction: to constitute an atlas of FDOPA uptake in the brainstem and diencephalon from images acquired in PET / MRI: the registration of the images on a reference model was carried out in MRI and then applied to PET images, the validation of the results taking place mainly in PET. Materials and Methods: we retrospectively selected 35 patients who underwent FDOPA PET/MRI: 15 considered as positive for dopaminergic denervation (visually decreased putaminal activity), 20 considered as normal (the control group). After reconstruction of the tomographic sections, the T1 images of each patient were registered on the T1 images of a reference model where several anatomical regions had been previously identified. The registration was carried out in a progressive way, in non-deformable and then deformable mode, after creation of a mask including the brainstem, the diencephalon and the striatum. The registration parameters were then applied to the FDOPA images acquired 90 min after injection. The choice of the optimal method of registration was based on the analysis of the dispersion of the activity in the summed image of the control group. A score was created, multiplying each SUV of each voxel of a predefined area by the spatially corresponding SUV in the model. Eight areas of the brainstem were used to create the final score. We finally investigated the correlation between the scores of 70 deformable registrations and the ability of specific brain regions to discriminate, using those registrations, the parkinsonian from the normal patients. Results: visually the images of the brainstem, diencephalon and striatum are correctly replaced after registration in all patients, without deformation. No manual correction was needed. A significant inverse correlation (Pearson's coefficient; p-values less than 0,0001) was found between the 70 scores and the corresponding p-values of a Student t-test comparing the control and patient groups in 5 non-striatal regions: the epiphysis, the hypothalamus, the pulvinar, the raphe nuclei and the substantia nigra. Furthermore, using the registration method with the highest score, two of those regions (the substantia nigra and the hypothalamus) exceeded the level of signification. Those statistical characters were also observed in well validated regions in Parkinson's disease, the caudate and the putamen. Conclusion: using the hybrid PET/MRI technique, it is possible to reliably achieve an automatic analysis of FDOPA uptake in brainstem and diencephalon nuclei. The method is independent of the injected tracer, which broadens its scope

[en] Medical imaging has entered the molecular era with positron emission tomography (PET) using fluorodeoxyglucose (¹⁸F-FDG), a radioactive analogue of glucose, which has been available in hospitals for a decade. Although this technique plays a major role in diagnosing numerous diseases, it is lacking in specificity because glucose hypermetabolism is common to numerous pathological processes. PET offers far greater potential than imaging of ¹⁸F-FDG: any molecule labelled with ¹⁸F (or ¹¹C) can be an imaging bio-marker. The needs for bio-markers are significant: the future of therapeutic innovations - notably targeted therapies and immunotherapy - depends on the ability to identify responsive patients, assess the early response and detect the appearance of treatment resistance. The development of radiopharmaceuticals specific to a pathology or a therapy will enable these challenges to be addressed. The LOTUS project aims at developing an integrated and automated 'on-demand' radiosynthesis system, from the production of the radioisotope to syringe filling for patient injection. (A.C.)

[en] Complete text of publication follows: Aim/Introduction: FDOPA PET/CT is commonly used for the investigation of dopaminergic denervation, the diagnosis being based on striatal uptake. But other brain structures, including monoaminergic neurons of the brainstem and diencephalon, metabolize FDOPA and are likely to be affected. Using the values automatically generated by a homemade PET / MRI atlas, we looked for alterations in the FDOPA uptake in parkinsonian syndromes. We retrospectively selected 120 patients who underwent FDOPA PET/MRI examination, 49 with Parkinson's syndrome according to clinical and scintigraphic data, 71 others considered very unlikely to have this condition (the control group). Materials and Methods: the T1 images of each patient were registered on the T1 images of a model where 28 anatomical regions had been previously identified. The adjustment parameters were then applied to FDOPA images acquired 90 min after injection. In each region VOIs of different sizes were then generated: 1 voxel (1mm³), 27 voxels or a volume adapted to the size of the region to be studied. The mean SUV, alone or compared to that of the other regions, was used to distinguish the 2 groups, by the way of a Student's test. Results: the results were similar, using different sizes of VOIS. In the parkinsonian group, a significant reduction in SUV was observed in the substantia nigra (p = 0.002), amygdala (p = 0.01) and pulvinar (p = 0.03). We did not observe any significant difference in the A8 zone, the reticular or the raphe nuclei. In the supratentorial area, the occipital region was unaffected too, in contrast to the striatum. The best discriminations between parkinsonian and control groups, obtained by combining the activities of the whole regions, were provided by the difference between the SUV of, on the one hand, the putamen and, on the other hand, the A8 area, the hypothalamus, the pulvinar, the substantia nigra and the caudate nucleus, all with p less than 10-20. Conclusion: for the first time in nuclear medicine, we think we have been able to automatically demonstrate the involvement of nuclei of the brainstem and diencephalon in Parkinson's syndrome. This opens perspectives in terms of early detection, staging and differential diagnosis of this disease

[en] Five years ago, PET/MRI hybrid imaging emerged. But, if PET/CT has become a worldwide imaging tool, the clinical usefulness of PET/MRI remains an open question, and its position beside PET/CT needs to be established. Many hurdles need to be overcome, like MRI-based attenuation correction or workflow considerations. The physical parameters provided by MRI applied to PET may significantly improve quantification and tissue characterisation, but this imaging revolution highly depends on the level of relevance that we expect from this type of hybrid imaging. (authors)

[en] Complete text of publication follows: Purpose: PET tumour segmentation is currently an active research topic in the field of radiotherapy planning and multi-parametric data quantification. Although being efficient on homogeneous spheroid-shaped tumours, classical threshold-based approaches are of limited value for heterogeneous or complex-shaped tumours, still making expert-based manual delineation the reference standard for tumour imaging, despite several limitations. In this context, the aim of this study was to assess the performances of an active contour-based approach for the PET segmentation of complex-shaped lung tumours, in comparison to an optimized expert-based manual reference standard. Subjects and Methods: Seventy-five thoracic tumours were segmented using the same graphical user interface (GUI) ITK snap software. For each tumour, an optimized expert-based reference standard was generated from the set of six independent expert-based manual segmentation results using the Simultaneous Truth And Performance Level Estimate (STAPLE) algorithm. In addition, four raters semi-automatically segmented the 75 PET tumours twice using the active contour based-procedure of the GUI software, with a delay time of one week between two segmentation sessions. For the 75 tumours, accuracy of the semi-automatic segmentations against the optimized expert-based reference standard was assessed using the DICE similarity coefficient (DSC). Inter-rater and intra-rater reliability analyses were performed using the intra class correlation coefficients (ICC) estimates of the output volumes, along with their 95% confidence intervals (two-way mixed-model, individual-rating, absolute-agreement). For all tumours segmentation procedures, average time per procedure was also estimated. Results: Overall accuracy of the semi-automatic procedure was excellent with a DSC of 0.835 (95%CI = 0.775-0.895). Inter-rater reliabilities provided the following results: ICC = 0.941 (95%CI = 0.913-0.961) for the first session and ICC = 0.935 (95%CI = 0.906- 0.956) for the second session. Intra-rater reliabilities provided the following results: ICC = 0.993 (95%CI = 0.990-0.996) for the rater 1; ICC = 0.987 (95%CI = 0.976-0.993) for the rater 2; ICC = 0.972 (95%CI = 0.956-0.982) for the rater 3; and ICC = 0.977 (95%CI = 0.964-0.985) for the rater 4. Average time was 631 seconds for manual segmentation procedure and 130 seconds for active contour-based. Conclusions: Compared to the state of the art expert-based manual segmentation, the GUI-based active contour procedure provided excellent accuracy and reliability, with a mean procedure duration almost five-times faster than the manual reference procedure. ITK snap software is robust, fast, and easy enough to be routinely applied as a powerful alternative to the manual reference standard in this setting

[en] Complete text of publication follows: Aim/Introduction: To assess the feasibility of a fully integrated dynamic PET-MRI approach applied to the characterization of lung lesions specifically. Materials and Methods: A total of 9 patients underwent a one-hour dynamic PET-MRI imaging protocol for suspected lung cancer. FDG PET and DCE MRI full kinetic analyses (Sokoloff and extended Toft models respectively), together with DWI-ADC and T1/T2-mapping were performed. All the PET-MRI data were warped into the same isotropic reference space before analyses. For each lung lesion, voxel-wise 3D maps of 14 biological features / 4 main categories were computed using an in-house fully integrative multimodal post-processing pipeline developed for this purpose specifically : perfusion/vascularization (K_trans, K_ep, V_e and V_p); metabolism (SUV, k1, k2, k3, Ki, V_b, and MRGlu); diffusion (ADC); and tissular characterization (T1 and T2 mapping). For each lesion, voxel-wise monotonic relationships between all the PET-MRI features were explored (Spearman correlations). Finally, all the lesions were partitioned by using multidimensional unsupervised gaussian mixture approach, and features profiles/relationships were explored at the supervoxel regional level. Results: Relationships between the perfusion/vascularization, metabolism, diffusion and tissular feature categories differed among the lesions. At the feature level, strong correlations (absolute r value superior to 0.5) were observed for the perfusion/vascularization features pairs and the metabolic feature pairs. At the category level, absolute r values were inferior to 0.5 for the vast majority of the feature pairs. Combining the 14 features together, unsupervised clustering provided 2 to 4 supervoxels depending on the lesion. At the supervoxel regional levels, feature profiles differed, as well as their monotonic relationships. Conclusion: Our one-stop-shop fully integrative dynamic PETMRI protocol provided 14 biological features (4 main categories) in the same examination. For all lesions, the heterogeneity of features profiles/relationships at the regional supervoxel level highlights the unique capability of PET-MRI to get better insight of the biological characterization of lung masses

[en] Complete text of publication follows: Aim/Introduction: To evaluate the impact of geometric distortions inherent to diffusion weighted imaging (DWI) in the field of PET-MRI lung oncology. Materials and Methods: 10 patients were prospectively recruited and underwent an ¹⁸F-FDG PET-MRI for lung oncology purpose. For all patients, the imaging protocol included several thoracic PET-MRI acquisitions: a PET acquisition performed one hour after the intra veinous injection of ¹⁸F-FDG; a set of DWI acquisitions with anteroposterior phase encoding (b values of 0,500, 800 s/mm²) and reverse-phase encoding polarity (b value = 0 s/mm²); a high resolution post contrast-enhanced 3DT1-weighted FSPGR sequence. DWI data were corrected for geometric distortions using the reverse phase encoding method. All the DWI data (non corrected and corrected from the distortion) were warped to the same T1 weighted PET-MRI isotropic reference space before analyses. Quality of the co-registrations to the reference T1 PET-MRI was quantitatively assessed using mutual information metric. The percentage gain compared to non-warped DWI data was also computed. ADC feature maps of each lung lesion were computed from the DWI data non-corrected and corrected from the distortion, and voxel-wise percent differences together with paired t-test were computed. Finally, regional ADC-SUV monotonic correlations were explored from optimal realigned DWI-PET data. Results: Quality of the co-registration between DWI and T1 PET-MRI data was significantly improved by the reverse phase encoding method (relative gain on mutual information compared to non-warped DWI data : 4-46%, vs 0.4-27% for warped data without distortion correction, p inferior to 0.05). The between-ADC feature maps regional differences ranged from -100% to more than +150%. Regional correlations between ADC and SUV computed from optimal realigned DWIPET data revealed only weak monotonic relationships between the two features at the voxel level (Spearman coefficients inferior to 0.5 in all the cases). Conclusion: DWI-related distortions are significant in thoracic PET-MRI, and should be corrected for accurate DWI-PET multimodal analyses. ADC and SUV showed weak monotonic relationship at the voxel level, emphasizing their complementarity