MRI atlas of the pituitary gland in young female adults.

The probabilistic topography and inter-individual variability of the pituitary gland (PG) remain undetermined. The absence of a standardized reference atlas hinders research on PG volumetrics. In this study, we aimed at creating maximum probability maps for the anterior and posterior PG in young female adults. We manually delineated the anterior and posterior parts of the pituitary glands in 26 healthy subjects using high-resolution MRI T1 images. A three-step procedure and a cost function-masking approach were employed to optimize spatial normalization for the PG. We generated probabilistic atlases and maximum probability maps, which were subsequently coregistered back to the subjects' space and compared to manual delineations. Manual measurements led to a total pituitary volume of 705 ± 88 mm³, with the anterior and posterior volumes measuring 614 ± 82 mm³ and 91 ± 20 mm³, respectively. The mean relative volume difference between manual and atlas-based estimations was 1.3%. The global pituitary atlas exhibited an 80% (± 9%) overlap for the DICE index and 67% (± 11%) for the Jaccard index. Similarly, these values were 77% (± 13%) and 64% (± 14%) for the anterior pituitary atlas and 62% (± 21%) and 47% (± 17%) for the posterior PG atlas, respectively. We observed a substantial concordance and a significant correlation between the volume estimations of the manual and atlas-based methods for the global pituitary and anterior volumes. The maximum probability maps of the anterior and posterior PG lay the groundwork for automatic atlas-based segmentation methods and the standardized analysis of large PG datasets.

Preoperative 11 C-Methionine PET-MRI in Pediatric Infratentorial Tumors.

PURPOSE: MRI is the main imaging modality for pediatric brain tumors, but amino acid PET can provide additional information. Simultaneous PET-MRI acquisition allows to fully assess the tumor and lower the radiation exposure. Although symptomatic posterior fossa tumors are typically resected, the patient management is evolving and will benefit from an improved preoperative tumor characterization. We aimed to explore, in children with newly diagnosed posterior fossa tumor, the complementarity of the information provided by amino acid PET and MRI parameters and the correlation to histopathological results. PATIENTS AND METHODS: Children with a newly diagnosed posterior fossa tumor prospectively underwent a preoperative 11 C-methionine (MET) PET-MRI. Images were assessed visually and semiquantitatively. Using correlation, minimum apparent diffusion coefficient (ADC min ) and contrast enhancement were compared with MET SUV max . The diameter of the enhancing lesions was compared with metabolic tumoral volume. Lesions were classified according to the 2021 World Health Organization (WHO) classification. RESULTS: Ten children were included 4 pilocytic astrocytomas, 2 medulloblastomas, 1 ganglioglioma, 1 central nervous system embryonal tumor, and 1 schwannoma. All lesions showed visually increased MET uptake. A negative moderate correlation was found between ADC min and SUV max values ( r = -0.39). Mean SUV max was 3.8 (range, 3.3-4.2) in WHO grade 4 versus 2.5 (range, 1.7-3.0) in WHO grade 1 lesions. A positive moderate correlation was found between metabolic tumoral volume and diameter values ( r = 0.34). There was no correlation between SUV max and contrast enhancement intensity ( r = -0.15). CONCLUSIONS: Preoperative 11 C-MET PET and MRI could provide complementary information to characterize pediatric infratentorial tumors.

Structure-function relationship of the pituitary gland in anorexia nervosa and intense physical activity.

Patients with Anorexia Nervosa (AN) and athletes share intense physical activity and pituitary hormonal disturbances related to absolute (AN) or relative (athletes) undernutrition. Pituitary gland (PG) structure evaluations in those conditions are scarce, and did not differentiate anterior from posterior lobe. We evaluated the structure-function relationship of anterior and posterior PG in AN and athletes, and potential reversibility of this alteration in a group of weight-recovered patients (AN_Rec). Manual delineation of anterior (AP) and posterior (PP) PG was performed on T1-weighted MR images in 17 women with AN, 15 women with AN_Rec, 18 athletes women and 25 female controls. Anthropometric, hormonal, and psychometric parameters were explored and correlated with PG volumes. AP volume (APV) was lower in AN (448 ± 82 mm3), AN_Rec (505 ± 59 mm3), and athletes (540 ± 101 mm3) vs. Controls (615 ± 61 mm3, p < 0.00001, p < 0.00001 and p = 0.02, respectively); and smaller in AN vs. AN_Rec (p = 0.007). PP volume did not show any differences between the groups. APV was positively correlated with weight (R = 0.36, p = 0.011) in AN, and luteinizing hormone (R = 0.35, p = 0.014) in total group. In AN, mean growth hormone (GH) was negatively correlated with global pituitary volume (R = 0.31, p = 0.031) and APV (R = 0.29, p = 0.037). Absolute and relative undernutrition led to a decreased anterior pituitary gland volume, which was reversible with weight gain, correlated with low bodyweight, and blockade of gonadal hypothalamic-pituitary axis. Intriguing inverse correlation between anterior pituitary gland volume and GH plasma level could suggests a low storage capacity of anterior pituitary gland and increased reactivity to low insulin-like growth factor type 1.

Noradrenergic alterations in Parkinson's disease: a combined 11C-yohimbine PET/neuromelanin MRI study.

Degeneration of the noradrenergic system is now considered a pathological hallmark of Parkinson's disease, but little is known about its consequences in terms of parkinsonian manifestations. Here, we evaluated two aspects of the noradrenergic system using multimodal in vivo imaging in patients with Parkinson's disease and healthy controls: the pigmented cell bodies of the locus coeruleus with neuromelanin sensitive MRI; and the density of α2-adrenergic receptors (ARs) with PET using 11C-yohimbine. Thirty patients with Parkinson's disease and 30 age- and sex-matched healthy control subjects were included. The characteristics of the patients' symptoms were assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Patients showed reduced neuromelanin signal intensity in the locus coeruleus compared with controls and diminished 11C-yohimbine binding in widespread cortical regions, including the motor cortex, as well as in the insula, thalamus and putamen. Clinically, locus coeruleus neuronal loss was correlated with motor (bradykinesia, motor fluctuations, tremor) and non-motor (fatigue, apathy, constipation) symptoms. A reduction of α2-AR availability in the thalamus was associated with tremor, while a reduction in the putamen, the insula and the superior temporal gyrus was associated with anxiety. These results highlight a multifaceted alteration of the noradrenergic system in Parkinson's disease since locus coeruleus and α2-AR degeneration were found to be partly uncoupled. These findings raise important issues about noradrenergic dysfunction that may encourage the search for new drugs targeting this system, including α2-ARs, for the treatment of Parkinson's disease.

The PREMISE database of 20 Macaca fascicularis PET/MRI brain images available for research.

Non-human primate studies are unique in translational research, especially in neurosciences where neuroimaging approaches are the preferred methods used for cross-species comparative neurosciences. In this regard, neuroimaging database development and sharing are encouraged to increase the number of subjects available to the community, while limiting the number of animals used in research. Here we present a simultaneous positron emission tomography (PET)/magnetic resonance (MR) dataset of 20 Macaca fascicularis images structured according to the Brain Imaging Data Structure standards. This database contains multiple MR imaging sequences (anatomical, diffusion and perfusion imaging notably), as well as PET perfusion and inflammation imaging using respectively [15O]H2O and [11C]PK11195 radiotracers. We describe the pipeline method to assemble baseline data from various cohorts and qualitatively assess all the data using signal-to-noise and contrast-to-noise ratios as well as the median of intensity and the pseudo-noise-equivalent-count rate (dynamic and at maximum) for PET data. Our study provides a detailed example for quality control integration in preclinical and translational PET/MR studies with the aim of increasing reproducibility. The PREMISE database is stored and available through the PRIME-DE consortium repository.

Characterisation of a novel [18F]FDG brain PET database and combination with a second database for optimising detection of focal abnormalities, using focal cortical dysplasia as an example.

BACKGROUND: Brain [18F]FDG PET is used clinically mainly in the presurgical evaluation for epilepsy surgery and in the differential diagnosis of neurodegenerative disorders. While scans are usually interpreted visually on an individual basis, comparison against normative cohorts allows statistical assessment of abnormalities and potentially higher sensitivity for detecting abnormalities. Little work has been done on out-of-sample databases (acquired differently to the patient data). Combination of different databases would potentially allow better power and discrimination. We fully characterised an unpublished healthy control brain [18F]FDG PET database (Marseille, n = 60, ages 21-78 years) and compared it to another publicly available database (MRXFDG, n = 37, ages 23-65 years). We measured and then harmonised spatial resolution and global values. A collection of patient scans (n = 34, 13-48 years) with histologically confirmed focal cortical dysplasias (FCDs) obtained on three generations of scanners was used to estimate abnormality detection rates using standard software (statistical parametric mapping, SPM12). RESULTS: Regional SUVs showed similar patterns, but global values and resolutions were different as expected. Detection rates for the FCDs were 50% for comparison with the Marseille database and 53% for MRXFDG. Simply combining both databases worsened the detection rate to 41%. After harmonisation of spatial resolution, using a full factorial design matrix to accommodate global differences, and leaving out controls older than 60 years, we achieved detection rates of up to 71% for both databases combined. Detection rates were similar across the three scanner types used for patients, and high for patients whose MRI had been normal (n = 10/11). CONCLUSIONS: As expected, global and regional data characteristics are database specific. However, our work shows the value of increasing database size and suggests ways in which database differences can be overcome. This may inform analysis via traditional statistics or machine learning, and clinical implementation.

3D-printed dual holder system for simultaneous rat PET scanning: design and influence on quantification.

BACKGROUND: The low throughout of small animal positron emission tomography (PET) images acquisitions represents a substantial limitation. The aims of this study were (i) to design a low-cost support for simultaneous dynamic PET scanning of two lying rats and (ii) to study its impact on brain image quantification. RESULTS: Accuracy of concentration measurement was 5.5% for one phantom in the field of view, and 5.7% for two phantoms measured simultaneously. Ratio concentration between phantoms showed an error of 6.7% ± 5.1% for Solo upper position, 6.7% ± 3.7% for Solo lower position, 5.9% ± 4.3% for Duo upper position, and 7.4% ± 6% for Duo lower position 6.7% for separated measures, and 6.6% for simultaneous measures. In vivo distribution profiles showed no difference between solo and duo uptakes. Region of Interest quantification in the whole brain showed 4.4% variability solo and 3.5% duo. The quantified test-retest bias was 8% in solo and 5% in duo, and the Intraclass Correlation Coefficient was comparable in solo and duo (0.969 vs. 0.966). CONCLUSIONS: Our results showed that simultaneous scans of two rats in INVEON do not affect quantification. The dual support system will allow us to reduce protocol costs and duration.

Deep-learning predicted PET can be subtracted from the true clinical fluorodeoxyglucose PET co-registered to MRI to identify the epileptogenic zone in focal epilepsy.

OBJECTIVE: Normal interictal [18 F]FDG-PET can be predicted from the corresponding T1w MRI with Generative Adversarial Networks (GANs). A technique we call SIPCOM (Subtraction Interictal PET Co-registered to MRI) can then be used to compare epilepsy patients' predicted and clinical PET. We assessed the ability of SIPCOM to identify the Resection Zone (RZ) in patients with drug-resistant epilepsy (DRE) with reference to visual and statistical parametric mapping (SPM) analysis. METHODS: Patients with complete presurgical work-up and subsequent SEEG and cortectomy were included. RZ localisation, the reference region, was assigned to one of eighteen anatomical brain regions. SIPCOM was implemented using healthy controls to train a GAN. To compare, the clinical PET coregistered to MRI was visually assessed by two trained readers, and a standard SPM analysis was performed. RESULTS: Twenty patients aged 17-50 (32 ± 7.8) years were included, 14 (70%) with temporal lobe epilepsy (TLE). Eight (40%) were MRI-negative. After surgery, 14 patients (70%) had a good outcome (Engel I-II). RZ localisation rate was 60% with SIPCOM vs 35% using SPM (P = 0.015) and vs 85% using visual analysis (P = 0.54). Results were similar for Engel I-II patients, the RZ localisation rate was 64% with SIPCOM vs 36% with SPM. With SIPCOM localisation was correct in 67% in MRI-positive vs 50% in MRI-negative patients, and 64% in TLE vs 43% in extra-TLE. The average number of false-positive clusters was 2.2 ± 1.3 using SIPCOM vs 2.3 ± 3.1 using SPM. All RZs localized with SPM were correctly localized with SIPCOM. In one case, PET and MRI were visually reported as negative, but both SIPCOM and SPM localized the RZ. SIGNIFICANCE: SIPCOM performed better than the reference computer-assisted method (SPM) for RZ detection in a group of operated DRE patients. SIPCOM's impact on epilepsy management needs to be prospectively validated.

Distribution of α2-Adrenergic Receptors in the Living Human Brain Using [11C]yohimbine PET.

The neurofunctional basis of the noradrenergic (NA) system and its associated disorders is still very incomplete because in vivo imaging tools in humans have been missing up to now. Here, for the first time, we use [11C]yohimbine in a large sample of subjects (46 healthy volunteers, 23 females, 23 males; aged 20-50) to perform direct quantification of regional alpha 2 adrenergic receptors' (α2-ARs) availability in the living human brain. The global map shows the highest [11C]yohimbine binding in the hippocampus, the occipital lobe, the cingulate gyrus, and the frontal lobe. Moderate binding was found in the parietal lobe, thalamus, parahippocampus, insula, and temporal lobe. Low levels of binding were found in the basal ganglia, the amygdala, the cerebellum, and the raphe nucleus. Parcellation of the brain into anatomical subregions revealed important variations in [11C]yohimbine binding within most structures. Strong heterogeneity was found in the occipital lobe, the frontal lobe, and the basal ganglia, with substantial gender effects. Mapping the distribution of α2-ARs in the living human brain may prove useful not only for understanding the role of the NA system in many brain functions, but also for understanding neurodegenerative diseases in which altered NA transmission with specific loss of α2-ARs is suspected.

Design of a generic method for single dual-tracer PET imaging acquisition in clinical routine.

Using different tracers in positron emission tomography (PET) imaging can bring complementary information on tumor heterogeneities. Ideally, PET images of different tracers should be acquired simultaneously to avoid the bias induced by movement and physiological changes between sequential acquisitions. Previous studies have demonstrated the feasibility of recovering separated PET signals or parameters of two or more tracers injected (quasi-)simultaneously in a single acquisition. In this study, a generic framework in the context of dual-tracer PET acquisition is proposed where no strong kinetic assumptions nor specific tuning of parameters are required. The performances of the framework were assessed through simulations involving the combination of [18F]FCH and [18F]FDG injections, two protocols (90 and 60 min acquisition durations) and various activity ratios between the two injections. Preclinical experiments with the same radiotracers were also conducted. Results demonstrate the ability of the method both to extract separated arterial input functions (AIF) from noisy image-derived input function and to separate the dynamic signals and further estimate kinetic parameters. The compromise between bias and variance associated with the estimation of net influx rateKishows that it is preferable to use the second injected radiotracer with twice the activity of the first for both 90 min [18F]FCH+[18F]FDG and 60 min [18F]FDG+[18F]FCH protocols. In these optimal settings, the weighted mean-squared-error of the estimated AIF was always less than 7%. TheKibias was similar to the one of single-tracer acquisitions; below 5%. Compared to single-tracer results, the variance ofKiwas twice more for 90 min dual-tracer scenario and four times more for the 60 min scenario. The generic design of the method makes it easy to use for other pairs of radiotracers and even for more than two tracers. The absence of strong kinetic assumptions and tuning parameters makes it suitable for a possible use in clinical routine.

Spatio-Temporal Characterization of Brain Inflammation in a Non-human Primate Stroke Model Mimicking Endovascular Thrombectomy.

Reperfusion therapies in acute ischemic stroke have demonstrated their efficacy in promoting clinical recovery. However, ischemia/reperfusion injury and related inflammation remain a major challenge in patient clinical management. We evaluated the spatio-temporal evolution of inflammation using sequential clinical [11C]PK11195 PET-MRI in a non-human primate (NHP) stroke model mimicking endovascular thrombectomy (EVT) with a neuroprotective cyclosporine A (CsA) treatment. The NHP underwent a 110-min transient endovascular middle cerebral artery occlusion. We acquired [11C]PK11195 dynamic PET-MR imaging at baseline, 7 and 30 days after intervention. Individual voxel-wise analysis was performed thanks to a baseline scan database. We quantified [11C]PK11195 in anatomical regions and in lesioned areas defined on per-occlusion MR diffusion-weighted imaging and perfusion [15O2]H2OPET imaging. [11C]PK11195 parametric maps showed a clear uptake overlapping the lesion core at D7, which further increased at D30. Voxel-wise analysis identified individuals with significant inflammation at D30, with voxels located within the most severe diffusion reduction area during occlusion, mainly in the putamen. The quantitative analysis revealed that thalamic inflammation lasted until D30 and was significantly reduced in the CsA-treated group compared to the placebo. In conclusion, we showed that chronic inflammation matched ADC decrease at occlusion time, a region exposed to an initial burst of damage-associated molecular patterns, in an NHP stroke model mimicking EVT. We described secondary thalamic inflammation and the protective effect of CsA in this region. We propose that major ADC drop in the putamen during occlusion may identify individuals who could benefit from early personalized treatment targeting inflammation.

Efficacy and auditory biomarker analysis of fronto-temporal transcranial direct current stimulation (tDCS) in targeting cognitive impairment associated with recent-onset schizophrenia: study protocol for a multicenter randomized double-blind sham-controlled trial.

BACKGROUND: In parallel to the traditional symptomatology, deficits in cognition (memory, attention, reasoning, social functioning) contribute significantly to disability and suffering in individuals with schizophrenia. Cognitive deficits have been closely linked to alterations in early auditory processes (EAP) that occur in auditory cortical areas. Preliminary evidence indicates that cognitive deficits in schizophrenia can be improved with a reliable and safe non-invasive brain stimulation technique called tDCS (transcranial direct current stimulation). However, a significant proportion of patients derive no cognitive benefits after tDCS treatment. Furthermore, the neurobiological mechanisms of cognitive changes after tDCS have been poorly explored in trials and are thus still unclear. METHOD: The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, multicenter trial. Sixty participants with recent-onset schizophrenia and cognitive impairment will be randomly allocated to receive either active (n=30) or sham (n=30) tDCS (20-min, 2-mA, 10 sessions during 5 consecutive weekdays). The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left auditory cortex. Cognition, tolerance, symptoms, general outcome and EAP (measured with EEG and multimodal MRI) will be assessed prior to tDCS (baseline), after the 10 sessions, and at 1- and 3-month follow-up. The primary outcome will be the number of responders, defined as participants demonstrating a cognitive improvement ≥Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score at 1-month follow-up. Additionally, we will measure how differences in EAP modulate individual cognitive benefits from active tDCS and whether there are changes in EAP measures in responders after active tDCS. DISCUSSION: Besides proposing a new fronto-temporal tDCS protocol by targeting the auditory cortical areas, we aim to conduct a randomized controlled trial (RCT) with follow-up assessments up to 3 months. In addition, this study will allow identifying and assessing the value of a wide range of neurobiological EAP measures for predicting and explaining cognitive deficit improvement after tDCS. The results of this trial will constitute a step toward the use of tDCS as a therapeutic tool for the treatment of cognitive impairment in recent-onset schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05440955. Prospectively registered on July 1st, 2022.

[18F]F13640: a selective agonist PET radiopharmaceutical for imaging functional 5-HT1A receptors in humans.

PURPOSE: F13640 (a.k.a. befiradol, NLX-112) is a highly selective 5-HT1A receptor ligand that was selected as a PET radiopharmaceutical-candidate based on animal studies. Due to its high efficacy agonist properties, [18F]F13640 binds preferentially to functional 5-HT1A receptors, which are coupled to intracellular G-proteins. Here, we characterize brain labeling of 5-HT1A receptors by [18F]F13640 in humans and describe a simplified model for its quantification. METHODS: PET/CT and PET-MRI scans were conducted in a total of 13 healthy male volunteers (29 ± 9 years old), with arterial input functions (AIF) (n = 9) and test-retest protocol (n = 8). Several kinetic models were compared (one tissue compartment model, two-tissue compartment model, and Logan); two models with reference region were also evaluated: simplified reference tissue model (SRTM) and the logan reference model (LREF). RESULTS: [18F]F13640 showed high uptake values in raphe nuclei and cortical regions. SRTM and LREF models showed a very high correlation with kinetic models using AIF. As concerns test-retest parameters and the prolonged binding kinetics of [18F]F13640, better reproducibility, and reliability were found with the LREF method. Cerebellum white matter and frontal lobe white matter stand out as suitable reference regions. CONCLUSION: The favorable brain labeling and kinetic profile of [18F]F13640, its high receptor specificity and its high efficacy agonist properties open new perspectives for studying functionally active 5-HT1A receptors, unlike previous radiopharmaceuticals that act as antagonists. [18F]F13640's kinetic properties allow injection outside of the PET scanner with delayed acquisitions, facilitating the design of innovative longitudinal protocols in neurology and psychiatry. TRIAL REGISTRATION: Trial Registration EudraCT 2017-002,722-21.

Prone position decreases acute lung inflammation measured by [11C](R)-PK11195 positron emission tomography in experimental acute respiratory distress syndrome.

Whether prone positioning (PP) modulates acute lung inflammation by the modulation of biomechanical forces of ventilator-induced lung injuries (VILIs) remains unclear. We aimed to demonstrate that PP decreases acute lung inflammation in animals with experimental acute respiratory distress syndrome (ARDS). Animals were under general anesthesia and protective ventilation (tidal volume 6 mL·kg-1, PEEP 5 cmH2O). ARDS was induced by intratracheal instillation of chlorohydric acid. Animals were then randomized to PP, or to supine position (SP). After 4 h, a positron emission tomography (PET) acquisition with [11C](R)-PK11195 was performed coupled with computerized tomography (CT) acquisitions, allowing the CT quantification of VILI-associated parameters. [11C](R)-PK11195 lung uptake was quantified using pharmacokinetic multicompartment models. Analyses were performed on eight lung sections distributed along the antero-posterior dimension. Six animals were randomized to PP, five to SP (median [Formula: see text]/[Formula: see text] [interquartile range]: 164 [102-269] mmHg). The normally aerated compartment was significantly redistributed to the posterior lung regions of animals in PP, compared with SP. Dynamic strain was significantly increased in posterior regions of SP animals, compared with PP. After 4 h, animals in PP had a significantly lower uptake of [11C](R)-PK11195, compared with SP. [11C](R)-PK11195 regional uptake was independently associated with the study group, dynamic strain, tidal hyperinflation, and regional respiratory system compliance in multivariate analysis. In an experimental model of ARDS, 4 h of PP significantly decreased acute lung inflammation assessed with PET. The beneficial impact of PP on acute lung inflammation was consecutive to the combination of decreased biomechanical forces and changes in the respiratory system mechanics.NEW & NOTEWORTHY Prone position decreases acute lung macrophage inflammation quantified in vivo with [11C](R)-PK11195 positron emission tomography in an experimental acute respiratory distress syndrome. Regional macrophage inflammation is maximal in the most anterior and posterior lung section of supine animals, in relation with increased regional tidal strain and hyperinflation, and reduced regional lung compliance.

PET image enhancement using artificial intelligence for better characterization of epilepsy lesions.

Introduction: [18F]fluorodeoxyglucose ([18F]FDG) brain PET is used clinically to detect small areas of decreased uptake associated with epileptogenic lesions, e.g., Focal Cortical Dysplasias (FCD) but its performance is limited due to spatial resolution and low contrast. We aimed to develop a deep learning-based PET image enhancement method using simulated PET to improve lesion visualization. Methods: We created 210 numerical brain phantoms (MRI segmented into 9 regions) and assigned 10 different plausible activity values (e.g., GM/WM ratios) resulting in 2100 ground truth high quality (GT-HQ) PET phantoms. With a validated Monte-Carlo PET simulator, we then created 2100 simulated standard quality (S-SQ) [18F]FDG scans. We trained a ResNet on 80% of this dataset (10% used for validation) to learn the mapping between S-SQ and GT-HQ PET, outputting a predicted HQ (P-HQ) PET. For the remaining 10%, we assessed Peak Signal-to-Noise Ratio (PSNR), Structural Similarity Index Measure (SSIM), and Root Mean Squared Error (RMSE) against GT-HQ PET. For GM and WM, we computed recovery coefficients (RC) and coefficient of variation (COV). We also created lesioned GT-HQ phantoms, S-SQ PET and P-HQ PET with simulated small hypometabolic lesions characteristic of FCDs. We evaluated lesion detectability on S-SQ and P-HQ PET both visually and measuring the Relative Lesion Activity (RLA, measured activity in the reduced-activity ROI over the standard-activity ROI). Lastly, we applied our previously trained ResNet on 10 clinical epilepsy PETs to predict the corresponding HQ-PET and assessed image quality and confidence metrics. Results: Compared to S-SQ PET, P-HQ PET improved PNSR, SSIM and RMSE; significatively improved GM RCs (from 0.29 ± 0.03 to 0.79 ± 0.04) and WM RCs (from 0.49 ± 0.03 to 1 ± 0.05); mean COVs were not statistically different. Visual lesion detection improved from 38 to 75%, with average RLA decreasing from 0.83 ± 0.08 to 0.67 ± 0.14. Visual quality of P-HQ clinical PET improved as well as reader confidence. Conclusion: P-HQ PET showed improved image quality compared to S-SQ PET across several objective quantitative metrics and increased detectability of simulated lesions. In addition, the model generalized to clinical data. Further evaluation is required to study generalization of our method and to assess clinical performance in larger cohorts.

Non-invasive quantification of acute macrophagic lung inflammation with [11C](R)-PK11195 using a three-tissue compartment kinetic model in experimental acute respiratory distress syndrome.

PURPOSE: Imaging of acute lung inflammation is pivotal to evaluate innovative ventilation strategies. We aimed to develop and validate a three-tissue compartment kinetic model (3TCM) of [11C](R)-PK11195 lung uptake in experimental acute respiratory distress syndrome (ARDS) to help quantify macrophagic inflammation, while accounting for the impact of its non-specific and irreversible uptake in lung tissues. MATERIAL AND METHODS: We analyzed the data of 38 positron emission tomography (PET) studies performed in 21 swine with or without experimental ARDS, receiving general anesthesia and mechanical ventilation. Model input function was a plasma, metabolite-corrected, image-derived input function measured in the main pulmonary artery. Regional lung analysis consisted in applying both the 3TCM and the two-tissue compartment model (2TCM); in each region, the best model was selected using a selection algorithm with a goodness-of-fit criterion. Regional best model binding potentials (BPND) were compared to lung macrophage presence, semi-quantified in pathology. RESULTS: The 3TCM was preferred in 142 lung regions (62%, 95% confidence interval: 56 to 69%). BPND determined by the 2TCM was significantly higher than the value computed with the 3TCM (overall median with interquartile range: 0.81 [0.44-1.33] vs. 0.60 [0.34-0.94], p < 0.02). Regional macrophage score was significantly associated with the best model BPND (p = 0.03). Regional BPND was significantly increased in the hyperinflated lung compartment, compared to the normally aerated one (median with interquartile range: 0.8 [0.6-1.7] vs. 0.6 [0.3-0.8], p = 0.03). CONCLUSION: To assess the intensity and spatial distribution of acute macrophagic lung inflammation in the context of experimental ARDS with mechanical ventilation, PET quantification of [11C](R)-PK11195 lung uptake was significantly improved in most lung regions using the 3TCM. This new methodology offers the opportunity to non-invasively evaluate innovative ventilatory strategies aiming at controlling acute lung inflammation.

Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid 18F-NaF PET/MRI.

BACKGROUND: Previous studies have suggested the role of microcalcifications in plaque vulnerability. This exploratory study sought to assess the potential of hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) using 18F-sodium fluoride (18F-NaF) to check simultaneously 18F-NaF uptake, a marker of microcalcifications, and morphological criteria of vulnerability. METHODS AND RESULTS: We included 12 patients with either recently symptomatic or asymptomatic carotid stenosis. All patients underwent 18F-NaF PET/MRI. 18F-NaF target-to-background ratio (TBR) was measured in culprit and nonculprit (including contralateral plaques of symptomatic patients) plaques as well as in other arterial walls. Morphological criteria of vulnerability were assessed on MRI. Mineral metabolism markers were also collected. 18F-NaF uptake was higher in culprit compared to nonculprit plaques (median TBR 2.6 [2.2-2.8] vs 1.7 [1.3-2.2]; P = 0.03) but was not associated with morphological criteria of vulnerability on MRI. We found a positive correlation between 18F-NaF uptake and calcium plaque volume and ratio but not with circulating tissue-nonspecific alkaline phosphatase (TNAP) activity and inorganic pyrophosphate (PPi) levels. 18F-NaF uptake in the other arterial walls did not differ between symptomatic and asymptomatic patients. CONCLUSIONS: 18F-NaF PET/MRI may be a promising tool for providing additional insights into the plaque vulnerability.

PET Metabolic Imaging of Time-Dependent Reorganization of Olfactory Cued Fear Memory Networks in Rats.

Memory consolidation involves reorganization at both the synaptic and system levels. The latter involves gradual reorganization of the brain regions that support memory and has been mostly highlighted using hippocampal-dependent tasks. The standard memory consolidation model posits that the hippocampus becomes gradually less important over time in favor of neocortical regions. In contrast, this reorganization of circuits in amygdala-dependent tasks has been less investigated. Moreover, this question has been addressed using primarily lesion or cellular imaging approaches thus precluding the comparison of recent and remote memory networks in the same animals. To overcome this limitation, we used microPET imaging to characterize, in the same animals, the networks activated during the recall of a recent versus remote memory in an olfactory cued fear conditioning paradigm. The data highlighted the drastic difference between the extents of the two networks. Indeed, although the recall of a recent odor fear memory activates a large network of structures spanning from the prefrontal cortex to the cerebellum, significant activations during remote memory retrieval are limited to the piriform cortex. These results strongly support the view that amygdala-dependent memories also undergo system-level reorganization, and that sensory cortical areas might participate in the long-term storage of emotional memories.

CERMEP-IDB-MRXFDG: a database of 37 normal adult human brain [18F]FDG PET, T1 and FLAIR MRI, and CT images available for research.

We present a database of cerebral PET FDG and anatomical MRI for 37 normal adult human subjects (CERMEP-IDB-MRXFDG). Thirty-nine participants underwent static [18F]FDG PET/CT and MRI, resulting in [18F]FDG PET, T1 MPRAGE MRI, FLAIR MRI, and CT images. Two participants were excluded after visual quality control. We describe the acquisition parameters, the image processing pipeline and provide participants' individual demographics (mean age 38 ± 11.5 years, range 23-65, 20 women). Volumetric analysis of the 37 T1 MRIs showed results in line with the literature. A leave-one-out assessment of the 37 FDG images using Statistical Parametric Mapping (SPM) yielded a low number of false positives after exclusion of artefacts. The database is stored in three different formats, following the BIDS common specification: (1) DICOM (data not processed), (2) NIFTI (multimodal images coregistered to PET subject space), (3) NIFTI normalized (images normalized to MNI space). Bona fide researchers can request access to the database via a short form.

Modeling [11C]yohimbine PET human brain kinetics with test-retest reliability, competition sensitivity studies and search for a suitable reference region.

Previous work introduced the [11C]yohimbine as a suitable ligand of central α2-adrenoreceptors (α2-ARs) for PET imaging. However, reproducibility of [11C]yohimbine PET measurements in healthy humans estimated with a simplified modeling method with reference region, as well as sensitivity of [11C]yohimbine to noradrenergic competition were not evaluated. The objectives of the present study were therefore to fill this gap. METHODS: Thirteen healthy humans underwent two [11C]yohimbine 90-minute dynamic scans performed on a PET-MRI scanner. Seven had arterial blood sampling with metabolite assessment and plasmatic yohimbine free fraction evaluation at the first scan to have arterial input function and test appropriate kinetic modeling. The second scan was a simple retest for 6 subjects to evaluate the test-retest reproducibility. For the remaining 7 subjects the second scan was a challenge study with the administration of a single oral dose of 150 µg of clonidine 90 min before the PET scan. Parametric images of α2-ARs distribution volume ratios (DVR) were generated with two non-invasive models: Logan graphical analysis with Reference (LREF) and Simplified Reference Tissue Method (SRTM). Three reference regions (cerebellum white matter (CERWM), frontal white matter (FLWM), and corpus callosum (CC)) were tested. RESULTS: We showed high test-retest reproducibility of DVR estimation with LREF and SRTM regardless of reference region (CC, CERWM, FLWM). The best fit was obtained with SRTMCC (r2=0.94). Test-retest showed that the SRTMCC is highly reproducible (mean ICC>0.7), with a slight bias (-1.8%), whereas SRTMCERWM had lower bias (-0.1%), and excellent ICC (mean>0.8). Using SRTMCC, regional changes have been observed after clonidine administration with a significant increase reported in the amygdala and striatum as well as in several posterior cortical areas as revealed with the voxel-based analysis. CONCLUSION: The results add experimental support for the suitability of [11C]yohimbine PET in the quantitative assessment of α2-ARs occupancy in vivo in the human brain. Trial registration EudraCT 2018-000380-82.