Objectives:To explore in-vivo innate immune cell activation as a function of the distance from ventricular CSF in patients with Multiple Sclerosis (MS) using [18F]-DPA714 PET, and to investigate its relationship with periventricular microstructural damage, evaluated by magnetization transfer ratio (MTR), and with trajectories of disability worsening.Methods:Thirty-seven MS patients and nineteen healthy controls underwent MRI and [18F]-DPA714 TSPO dynamic PET, from which individual maps of voxels characterized by innate immune cell activation (DPA+) were generated. White matter (WM) was divided in 3mm-thick concentric rings radiating from the ventricular surface toward the cortex, and the percentage of DPA+ voxels and mean MTR were extracted from each ring. Two-year trajectories of disability worsening were collected to identify patients with and without recent disability worsening.Results:The percentage of DPA+ voxels was higher in patients compared to controls in the periventricular WM (p=6.10e-6), and declined with increasing distance from ventricular surface, with a steeper gradient in patients compared to controls (p=0.001). This gradient was found both in periventricular lesions and normal-appearing WM. In the total WM, it correlated with a gradient of microstructural tissue damage measured by MTR (rs=-0.65, p=1.0e-3). When compared to clinically stable patients, patients with disability worsening were characterized by a higher percentage of DPA+ voxels in the periventricular normal-appearing WM (p=0.025).Conclusions:Our results demonstrate that in MS the innate immune cell activation predominates in periventricular regions and associates with microstructural damage and disability worsening. This could result from the diffusion of pro-inflammatory CSF-derived factors into surrounding tissues.

Background To evaluate FCH‐PET/CT and parathyroid 4D‐CT so as to guide surgery in patients with primary hyperparathyroidism (pHPT) and prior neck surgery. Methods Medical records of all patients referred for a FCH‐PET/CT in our institution were systematically reviewed. Only patients with pHPT, a history of neck surgery (for pHPT or another reason) and an indication of reoperation were included. All patients had parathyroid ultrasound (US) and Tc‐99m‐sestaMIBI scintigraphy, and furthermore, some patients had 4D‐CT. Gold standard was defined by pathological findings and/or US‐guided fine‐needle aspiration with PTH level measurement in the washing liquid. Results Twenty‐nine patients were included in this retrospective study. FCH‐PET/CT identified 34 abnormal foci including 19 ectopic localizations. 4D‐CT, performed in 20 patients, detected 11 abnormal glands at first reading and 6 more under FCH‐PET/CT guidance. US and Tc‐99m‐sestaMIBI found concordant foci in 8/29 patients. Gold standard was obtained for 32 abnormal FCH‐PET/CT foci in 27 patients. On a per‐lesion analysis, sensitivity, specificity, positive and negative predictive values were, respectively, 96%, 13%, 77% and 50% for FCH‐PET/CT, 75%, 40%, 80% and 33% for 4D‐CT. On a per‐patient analysis, sensitivity was 85% for FCH‐PET/CT and 63% for 4D‐CT. FCH‐PET/CT results made it possible to successfully remove an abnormal gland in 21 patients, including 12 with a negative or discordant US/Tc‐99m‐sestaMIBI scintigraphy result, with a global cure rate of 73%. Conclusion FCH‐PET/CT is a promising tool in the challenging population of reoperative patients with pHPT. Parathyroid 4D‐CT appears as a confirmatory imaging modality.

To develop a novel approach to generate individual maps of white matter (WM) innate immune cell activation using 18 F-DPA-714 translocator protein (TSPO) positron emission tomography (PET), and to explore the relationship between these maps and individual trajectories of disability worsening in patients with multiple sclerosis (MS). Methods: Patients with MS (n=37), whose trajectories of disability worsening over the 2 years preceding study entry were calculated, and healthy controls (n=19) underwent magnetic resonance magnetic and 18 F-DPA-714 PET. A threshold of significant activation of 18 F-DPA-714 binding was calculated with a voxel-wise randomized permutation-based comparison between patients and controls, and used to classify each WM voxel in patients as characterized by a significant activation of innate immune cells (DPA+) or not. Individual maps of innate immune cell activation in the WM were employed to calculate the extent of activation in WM regions-of-interests and to classify each WM lesion as "DPA-active", "DPA-inactive" or "unclassified". Results: Compared with the WM of healthy controls, patients with MS had a significantly higher percentage of DPA+ voxels in the normal-appearing WM, (NAWM in patients=24.99.7%; WM in controls=14.07.8%, p<0.001). In patients with MS, the percentage of DPA+ voxels showed a significant increase from NAWM, to perilesional areas, T2 hyperintense lesions and T1 hypointense lesions (38.113.5%, 45.017.9%, and 51.922.9%, respectively, p<0.001). Among the 1379 T2 lesions identified, 512 were defined as DPAactive and 258 as DPA-inactive. A higher number of lesions classified as DPA-active (OR=1.13, p=0.009), a higher percentage of DPA+ voxels in the NAWM (OR=1.16, p=0.009) and in T1-spin-echo lesions (OR=1.06, p=0.036), were significantly associated by Imperial College London Library on February 11, 2020. For personal use only. jnm.snmjournals.org Downloaded from 2 with a retrospective more severe clinical trajectory in patients with MS. Conclusion: A more severe trajectory of disability worsening in MS is associated with an innate immune cells activation inside and around WM lesions. 18 F-DPA-714 PET may provide a promising biomarker to identify patients at risk of severe clinical trajectory.

DW-MRS showed a reduction in tCr diffusivity in the normal-appearing brain of patients with MS, which might reflect a state of ongoing energy dysregulation affecting neurons and/or glial cells. Reversing this energy dysregulation before neuro-axonal degeneration arises may become a key objective in future neuroprotective strategies.

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Kleine-Levin syndrome is a rare disorder characterized by relapsing-remitting episodes of severe hypersomnia, cognitive impairment, apathy, derealization and behavioural disturbances. Between episodes, most patients experience normal sleep, mood and behaviour, but they may have some residual abnormalities in brain functional imaging; however, the frequency, localisation and significance of abnormal imaging is unknown, as brain functional imaging have been scarce and heterogenous (including scintigraphy, [18F] fluorodeoxyglucose positron emission tomography/computerized tomography [FDG-PET/CT] and functional MRI during resting state and cognitive effort) and based on case reports or on group analysis in small groups. Using visual individual analysis of FDG-PET/CT at the time of Kleine-Levin syndrome diagnosis, we examined the frequency, localisation and clinical determinants of hypo- and hypermetabolism in a cross-sectional study. Among 179 patients with Kleine-Levin syndrome who underwent FDG-PET/CT, the visual analysis was restricted to the 138 untreated patients studied during asymptomatic periods. As many as 70% of patients had hypometabolism, mostly affecting the posterior associative cortex and the hippocampus. Hypometabolism was associated with younger age, recent (&lt;3 y) disease course, and a higher number of episodes during the preceding year. The hypometabolism was more extensive (from the left temporo-occipital junction to the entire homolateral and then the bilateral posterior associative cortex) at the beginning of the disorder. In contrast, there was hypermetabolism in the prefrontal dorsolateral cortex in half of the patients (almost all having concomitant hypometabolism in the posterior areas), which was also associated with younger age and shorter disease course. The cognitive performances (including episodic memory) were similar in patients with vs. without hippocampus hypometabolism. In conclusion, hypometabolism is frequently observed upon individual visual analysis of FDG-PET/CT during asymptomatic Kleine-Levin syndrome periods; it is mostly affecting the posterior associative cortex and the hippocampus and is mostly in young patients with recent onset disease. Hypometabolism provides a trait marker during the first years of Kleine-Levin syndrome, which could help clinicians during the diagnosis process.

BACKGROUND AND PURPOSE: PET/MRI with 18 F-FDG has demonstrated the advantages of simultaneous PET and MR imaging in head and neck cancer imaging, MRI allowing excellent soft-tissue contrast, while PET provides metabolic information. The aim of this study was to evaluate the added value of gadolinium contrast-enhanced sequences in the tumor delineation of head and neck cancers on 18 F-FDG-PET/MR imaging. MATERIALS AND METHODS:Consecutive patients who underwent simultaneous head and neck 18 F-FDG-PET/MR imaging staging or restaging followed by surgery were retrospectively included. Local tumor invasion and lymph node extension were assessed in 45 head and neck anatomic regions using 18 F-FDG-PET/MR imaging by 2 rater groups (each one including a radiologist and a nuclear medicine physician). Two reading sessions were performed, one without contrast-enhanced sequences (using only T1WI, T2WI, and PET images) and a second with additional T1WI postcontrast sequences. The results were compared with the detailed histopathologic analysis, used as reference standard. The k concordance coefficient between the reading sessions and sensitivity and specificity for each region were calculated.

Semantic variant of primary progressive aphasia (svPPA) is typically associated with non-Alzheimer's disease (AD) pathology. However, some anatomopathological studies have found AD lesions in those patients. We compared brain perfusion SPECT of 18 svPPA patients with CSF biomarkers indicative of non-Alzheimer pathology (svPPA-nonAD) and three svPPA patients with CSF biomarkers indicative of underlying AD (svPPA-AD). All svPPA patients had severe left temporopolar hypoperfusion. SvPPA-nonAD had additional anterior cingulate and mediofrontal hypoperfusion, whereas svPPA-AD had greater left parietal and posterior cingulate involvement. Parietal damage in svPPA constitutes a biomarker for underlying Alzheimer pathology thus refining the classification of this PPA variant.