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Abstract Background Dipeptidyl peptidase 3 (DPP3) is a ubiquitous cytosolic enzyme released into the bloodstream after tissue injury, that can degrade angiotensin II. High concentrations of circulating DPP3 (cDPP3) have been associated with worse outcomes during sepsis. The aim of this study was to assess the effect of Procizumab (PCZ), a monoclonal antibody that neutralizes cDPP3, in an experimental model of septic shock. Methods In this randomized, open-label, controlled study, 16 anesthetized and mechanically ventilated pigs with peritonitis were randomized to receive PCZ or standard treatment when the mean arterial pressure (MAP) dropped below 50 mmHg. Resuscitation with fluids, antimicrobial therapy, peritoneal lavage, and norepinephrine was initiated one hour later to maintain MAP between 65–75 mmHg for 12 h. Hemodynamic variables, tissue oxygenation indices, and measures of organ failure and myocardial injury were collected. Organ blood flow was assessed using isotopic assessment (99mtechnetium albumin). cDPP3 activity, equilibrium analysis of the renin–angiotensin system and circulating catecholamines were measured. Tissue mRNA expression of interleukin-6 and downregulation of adrenergic and angiotensin receptors were assessed on vascular and myocardial samples. Results PCZ-treated animals had reduced cDPP3 levels and required less norepinephrine and fluid than septic control animals for similar organ perfusion and regional blood flow. PCZ-treated animals had less myocardial injury, and higher PaO2/FiO2 ratios. PCZ was associated with lower circulating catecholamine levels; higher circulating angiotensin II and higher angiotensin II receptor type 1 myocardial protein expression, and with lower myocardial and radial artery mRNA interleukin-6 expression. Conclusions In an experimental model of septic shock, PCZ administration was associated with reduced fluid and catecholamine requirements, less myocardial injury and cardiovascular inflammation, along with preserved angiotensin II signaling. Graphical Abstract

Abstract Background Fibroblast activation protein-α (FAPα) is a marker of activated fibroblasts that can be selectively targeted by an inhibitor (FAPI) and visualised by PET/CT imaging. We evaluated whether the measurement of FAPα in bronchoalveolar lavage fluids (BALF) and the uptake of FAPI by PET/CT could be used as biomarkers of fibrogenesis. Methods The dynamics of lung uptake of 18F-labeled FAPI ([18F]FAPI-74) was assessed in the bleomycin mouse model at various time points and using different concentrations of bleomycin by PET/CT. FAPα was measured in BALFs from these bleomycin-treated and control mice. FAPα levels were also assessed in BALFs from controls and patients with idiopathic pulmonary fibrosis (IPF). Results Bleomycin-treated mice presented a significantly higher uptake of [18F]FAPI-74 during lung fibrinogenesis (days 10 and 16 after instillation) compared to control mice. No significant difference was observed at initial inflammatory phase (3 days) and when fibrosis was already established (28 days). [18F]FAPI-74 tracer was unable to show a dose-response to bleomycin treatment. On the other hand, BALF FAPα levels were steeply higher in bleomycin-treated mice at day 10 and a significant dose-response effect was observed. Moreover, FAPα levels were strongly correlated with lung fibrosis as measured by the modified Aschroft histological analysis, hydroxyproline and the percentage of weight loss. Importantly, higher levels of FAPα were observed in IPF patients where the disease was progressing as compared to stable patients and controls. Moreover, patients with FAPα BALF levels higher than 192.5 pg/mL presented a higher risk of progression, transplantation or death compared to patients with lower levels. Conclusions Our preclinical data highlight a specific increase of [18F]FAPI-74 lung uptake during the fibrotic phase of the bleomycin murine model. The measurement of FAPα in BALF appears to be a promising marker of the fibrotic activity in preclinical models of lung fibrosis and in IPF patients. Further studies are required to confirm the role of FAPα in BALF as biomarker of IPF activity and assess the relationship between FAPα levels in BALF and [18F]FAPI-74 uptake on PET/CT in patients with fibrotic lung disease.

Cryogenic magnetoencephalography (MEG) enhances the presurgical assessment of refractory focal epilepsy (RFE). Optically pumped magnetometers (OPMs) are cryogen-free sensors that enable on-scalp MEG recordings. Here, we investigate the application of tri-axial OPMs [87Rb (Rb-OPM) and 4He gas (He-OPM)] for the detection of interictal epileptiform discharges (IEDs). IEDs were recorded simultaneously with 4 tri-axial Rb- and 4 tri-axial He-OPMs in a child with RFE. IEDs were identified visually, isolated from magnetic background noise using independent component analysis (ICA) and were studied following their optimal magnetic field orientation thanks to virtual sensors. Most IEDs (>1,000) were detectable by both He- and Rb-OPM recordings. IEDs were isolated by ICA and the resulting magnetic field oriented mostly tangential to the scalp in Rb-OPMs and radial in He-OPMs. Likely due to differences in sensor locations, the IED amplitude was higher with Rb-OPMs. This case study shows comparable ability of Rb-OPMs and He-OPMs to detect IEDs and the substantial benefits of triaxial OPMs to detect IEDs from different sensor locations. Tri-axial OPMs allow to maximize spatial brain sampling for IEDs detection with a limited number of sensors.

Abstract Background Positron emission tomography/computed tomography (PET/CT) using radiotracers that bind to the prostate-specific membrane antigen (PSMA) is mainly used in biochemical recurring prostate cancer. The aim of our study was to assess the usefulness of 18F-JK-PSMA-7 PET/CT for local and nodal staging in patients with intermediate- and high-risk prostate cancer (PCa) prior to radical prostatectomy, as compared to conventional imaging techniques. Methods We enrolled a total of 10 patients with intermediate- and high-risk PCa diagnosed by multiparametric-MRI followed by systematic and targeted biopsies, eligible for radical prostatectomy with extended lymph node dissection. Clinical team was blind to the results of the pre-surgery 18F-JK-PSMA-7 PET/CT at times of clinical decision and surgery. One month post-surgery, 18F-JK-PSMA-7 PET/CT was repeated and the results of both scans were unblinded. A third 18F-JK-PSMA-7 PET/CT could be acquired at a later time point depending on PSA progression. Results All pre-surgery 18F-JK-PSMA-7 PET/CT was positive in the prostatic region, while MRI was negative in the prostate in one patient. We also detected positive pelvic lymph nodes in two patients (one high-risk, one intermediate-risk PCa) on pre-surgery and post-surgery 18F-JK-PSMA-7 PET/CT. No positive pelvic lymph nodes were reported on pre-surgical CT and MRI. 18F-JK-PSMA-7 PET/CT detected bladder involvement in one patient and seminal vesicles involvement in two patients; this malignant extension was undetected by the conventional imaging techniques. SUVmax in prostate lesions had an average value of 11.51 (range 6.90–21.49). SUVmean in prostate lesions had an average value of 7.59 (range 5.26–14.02). Conclusion This pilot study indicates that pre-surgery 18F-JK-PSMA-7 PET/CT provides valuable information in intermediate- and high-risk PCa, for surgery planning with curative intent.

Hypothyroidism is a common condition that cannot always be satisfactorily treated through continued hormone replacement. Here the authors report the generation of transplantable thyroid organoids derived from human embryonic stem cells that can restore plasma thyroid hormone in athyreotic mice.

Abstract Background Digital PET/CT systems make use of a new technology with higher sensitivity and other better technological features than the analog ones. They require adaptation of the trade-off between performance, tracer dose and acquisition time. The aim of the study was to explore the performance of 18F-JK-PSMA-7 imaging when performed on a digital PET/CT with an adapted protocol, in a population of patients with prostate cancer patients (PCa). Influence of previous therapy on PET/CT performance is generally disregarded in PSMA-based imaging, despite potential influence of hormono-chemotherapy on the target expression. This potential influence was also tested in this work. Methods A total of 54 PCa patients experiencing biochemical recurrence were included in the study, in which we analysed the diagnostic performance of digital 18F-JK-PSMA-7 PET/CT. Compared to our protocol applied for acquisition on an analog system, administered dose and acquisition time were reduced by 20% and 50% respectively. We specifically took into consideration the influence of previous treatments on recurrence detection. Results We detected overall 18F-JK-PSMA-7-positive lesions in 38/54 patients (70.3%). There was no statistically significant difference regarding the detection rate between the groups of patients who had hormono-chemotherapy any time after initial diagnosis and those who never got any hormonal or chemotherapeutic treatment. Regarding the SUV max values, there was not significant difference between the two groups of patients neither in pelvic ganglions nor in other metastatic sites or the prostate region. Conclusion 18F-JK-PSMA7 PET/CT with administered dose and acquisition time adapted to the digital technology provides valuable information in PCa patients with biochemical recurrence.

Children have more difficulty perceiving speech in noise than adults. Whether this difficulty relates to an immature processing of prosodic or linguistic elements of the attended speech is still unclear. To address the impact of noise on linguistic processing per se, we assessed how babble noise impacts the cortical tracking of intelligible speech devoid of prosody in school-aged children and adults.Twenty adults and twenty children (7-9 years) listened to synthesized French monosyllabic words presented at 2.5 Hz, either randomly or in 4-word hierarchical structures wherein 2 words formed a phrase at 1.25 Hz, and 2 phrases formed a sentence at 0.625 Hz, with or without babble noise. Neuromagnetic responses to words, phrases and sentences were identified and source-localized.Children and adults displayed significant cortical tracking of words in all conditions, and of phrases and sentences only when words formed meaningful sentences. In children compared with adults, the cortical tracking was lower for all linguistic units in conditions without noise. In the presence of noise, the cortical tracking was similarly reduced for sentence units in both groups, but remained stable for phrase units. Critically, when there was noise, adults increased the cortical tracking of monosyllabic words in the inferior frontal gyri and supratemporal auditory cortices but children did not.This study demonstrates that the difficulties of school-aged children in understanding speech in a multi-talker background might be partly due to an immature tracking of lexical but not supra-lexical linguistic units.

Reaction-diffusion models have been proposed for decades to capture the growth of gliomas. Nevertheless, these models require an initial condition: the tumor cell density distribution over the whole brain at diagnosis time. Several works have proposed to relate this distribution to abnormalities visible on magnetic resonance imaging (MRI). In this work, we verify these hypotheses by stereotactic histological analysis of a non-operated brain with glioblastoma using a 3D-printed slicer. Cell density maps are computed from histological slides using a deep learning approach. The density maps are then registered to a postmortem MR image and related to an MR-derived geodesic distance map to the tumor core. The relation between the edema outlines visible on T2-FLAIR MRI and the distance to the core is also investigated. Our results suggest that (i) the previously proposed exponential decrease of the tumor cell density with the distance to the core is reasonable but (ii) the edema outlines would not correspond to a cell density iso-contour and (iii) the suggested tumor cell density at these outlines is likely overestimated. These findings highlight the limitations of conventional MRI to derive glioma cell density maps and the need for other initialization methods for reaction-diffusion models to be used in clinical practice.

BackgroundOnly a few cases of acute disseminated encephalomyelitis (ADEM) following coronavirus disease 19 (COVID-19) vaccination have been described since the beginning of the vaccination campaign.ResultsHere we report the first case of central nervous system (CNS) demyelination with systemic inflammatory findings on whole body 19-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) following the ChAdOx1 nCoV-19 vaccine.ConclusionsClinicians should stay aware of potential new adverse events after immunization.

A 72-year-old woman, with anti-myeloperoxidase antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), presented with two episodes of spinal pachymeningitis (at two different levels 9 years apart, cervical in 2011 and dorso-lumbar in 2020) associated with aortitis and only demonstrated by F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). This association between aortitis and pachymeningitis in AAV appears exceptional. Moreover, the relapse of aortitis and pachymeningitis in 2020 was not accompanied by an increase in ANCA. This case demonstrates the value of 18F-FDG PET/CT in the management of AAV, providing evidence of the recurrence and distribution of lesions in various organs, including those with unexpected involvement.

Abstract Objective Friedreich ataxia (FRDA) is the commonest hereditary ataxia in Caucasians. Most patients are homozygous for expanded GAA triplet repeats in the first intron of the frataxin (FXN) gene, involved in mitochondrial iron metabolism. Here, we used magnetoencephalography (MEG) to characterize the main determinants of FRDA‐related changes in intrinsic functional brain architecture. Methods Five minutes of MEG signals were recorded at rest from 18 right‐handed FRDA patients (mean age 27 years, 9 females; mean SARA score: 21.4) and matched healthy individuals. The MEG connectome was estimated as resting‐state functional connectivity (rsFC) matrices involving 37 nodes from six major resting state networks and the cerebellum. Source‐level rsFC maps were computed using leakage‐corrected broad‐band (3–40 Hz) envelope correlations. Post hoc median‐split was used to contrast rsFC in FRDA patients with different clinical characteristics. Nonparametric permutations and Spearman rank correlation test were used for statistics. Results High rank correlation levels were found between rsFC and age of symptoms onset in FRDA mostly between the ventral attention, the default‐mode, and the cerebellar networks; patients with higher rsFC developing symptoms at an older age. Increased rsFC was found in FRDA with later age of symptoms onset compared to healthy subjects. No correlations were found between rsFC and other clinical parameters. Conclusion Age of symptoms onset is a major determinant of FRDA patients' intrinsic functional brain architecture. Higher rsFC in FRDA patients with later age of symptoms onset supports compensatory mechanisms for FRDA‐related neural network dysfunction and position neuromagnetic rsFC as potential marker of FRDA neural reserve.

Primary angiitis of the central nervous system (PACNS) is a rare inflammatory disease affecting central nervous system vessels. The diagnosis, which requires confirmation by brain biopsy, remains challenging due to unspecific clinical presentation and low specificity of imaging and laboratory exams. In these two pediatric biopsy-proven cases of svPACNS we demonstrate that brain positron emission tomography (PET) show a high metabolic activity that extends beyond brain MRI abnormalities. Therefore, combining MRI and PET abnormalities to adequately guide brain biopsy might increase the diagnostic yield of this rare condition.

Abstract This case report demonstrates the possible subclinical adrenal and pancreatic involvement in immunocompromised patients (in particular those with lymphoma) with a CMV infection and the role of whole‐body 18F‐FDG PET/CT in detecting these lesions.

Children with developmental coordination disorder (DCD) present lower abilities to acquire and execute coordinated motor skills. DCD is frequently associated with visual perceptual (with or without motor component) impairments. This magnetoencephalography (MEG) study compares the brain resting-state functional connectivity (rsFC) and spectral power of children with and without DCD.29 children with DCD and 28 typically developing (TD) peers underwent 2 × 5 min of resting-state MEG. Band-limited power envelope correlation and spectral power were compared between groups using a functional connectome of 59 nodes from eight resting-state networks. Correlation coefficients were calculated between fine and gross motor activity, visual perceptual and visuomotor abilities measures on the one hand, and brain rsFC and spectral power on the other hand. Nonparametric statistics were used.Significantly higher rsFC between nodes of the visual, attentional, frontoparietal, default-mode and cerebellar networks was observed in the alpha (maximum statistics, p = .0012) and the low beta (p = .0002) bands in children with DCD compared to TD peers. Lower visuomotor performance (copying figures) was associated with stronger interhemispheric rsFC within sensorimotor areas and power in the cerebellum (right lobule VIII).Children with DCD showed increased rsFC mainly in the dorsal extrastriate visual brain system and the cerebellum. However, this increase was not associated with their coordinated motor/visual perceptual abilities. This enhanced functional brain connectivity could thus reflect a characteristic brain trait of children with DCD compared to their TD peers. Moreover, an interhemispheric compensatory process might be at play to perform visuomotor task within the normative range.

Since nucleoside-modified mRNA vaccines strongly activate T follicular helper cells, it is important to explore the possible impact of approved SARS-CoV-2 mRNA vaccines on neoplasms affecting this cell type. Herein, we report and discuss unexpected rapid progression of lymphomatous lesions after administration of a BNT162b2 mRNA vaccine booster in a man recently diagnosed with AITL.

This magnetoencephalography (MEG) study investigates how procedural sequence learning performance is related to prior brain resting-state functional connectivity (rsFC), and to what extent sequence learning induces rapid changes in brain rsFC in school-aged children.Procedural learning was assessed in 30 typically developing children (mean age ± SD: 9.99 years ± 1.35) using a serial reaction time task (SRTT). During SRTT, participants touched as quickly and accurately as possible a stimulus sequentially or randomly appearing in one of the quadrants of a touchscreen. Band-limited power envelope correlation (brain rsFC) was applied to MEG data acquired at rest pre- and post-learning. Correlation analyses were performed between brain rsFC and sequence-specific learning or response time indices.Stronger pre-learning interhemispheric rsFC between inferior parietal and primary somatosensory/motor areas correlated with better subsequent sequence learning performance and faster visuomotor response time. Faster response time was associated with post-learning decreased rsFC within the dorsal extra-striate visual stream and increased rsFC between temporo-cerebellar regions.In school-aged children, variations in functional brain architecture at rest within the sensorimotor network account for interindividual differences in sequence learning and visuomotor performance. After learning, rapid adjustments in functional brain architecture are associated with visuomotor performance but not sequence learning skills.

The Free and Cued Selective Reminding Test (FCSRT) is a largely validated neuropsychological test for the identification of amnestic syndrome from the early stage of Alzheimer’s disease (AD). Previous electrophysiological data suggested a slowing down of the alpha rhythm in the AD-continuum as well as a key role of this rhythmic brain activity for episodic memory processes. This study therefore investigates the link between alpha brain activity and alterations in episodic memory as assessed by the FCSRT. For that purpose, 37 patients with altered FCSRT performance underwent a comprehensive neuropsychological assessment, supplemented by 18F-fluorodeoxyglucose positron emission tomography/structural magnetic resonance imaging (18FDG-PET/MR), and 10 min of resting-state magnetoencephalography (MEG). The individual alpha peak frequency (APF) in MEG resting-state data was positively correlated with patients’ encoding efficiency as well as with the efficacy of semantic cues in facilitating patients’ retrieval of previous stored word. The APF also correlated positively with patients’ hippocampal volume and their regional glucose consumption in the posterior cingulate cortex. Overall, this study demonstrates that alterations in the ability to learn and store new information for a relatively short-term period are related to a slowing down of alpha rhythmic activity, possibly due to altered interactions in the extended mnemonic system. As such, a decreased APF may be considered as an electrophysiological correlate of short-term episodic memory dysfunction accompanying pathological aging.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is characterized by a progressive and irreversible respiratory failure. Non-invasive markers of disease activity are essential for prognosis and evaluation of early response to anti-fibrotic treatments. Objectives The aims of this study were to determine whether fluorodeoxyglucose ([18F]-FDG) lung uptake is reduced after initiation of pirfenidone or nintedanib and to assess its possible use as a prognostic factor. Methods [18F]-FDG PET/CT was performed in IPF patients and in a murine model of pulmonary fibrosis. PET/CTs were performed at day 8 and day 15 post-instillation of bleomycin in pirfenidone- or vehicule-treated mice. In IPF patients, PET-CT was performed before and 3 months after the initiation of pirfenidone or nintedanib. Results In bleomycin-treated mice, pirfenidone significantly reduced the [18F]-FDG uptake compared to vehicule-treated mice at day 15 (p

In multiple sclerosis, the interplay of neurodegeneration, demyelination and inflammation leads to changes in neurophysiological functioning. This study aims to characterize the relation between reduced brain volumes and spectral power in multiple sclerosis patients and matched healthy subjects.During resting-state eyes closed, we collected magnetoencephalographic data in 67 multiple sclerosis patients and 47 healthy subjects, matched for age and gender. Additionally, we quantified different brain volumes through magnetic resonance imaging (MRI).First, a principal component analysis of MRI-derived brain volumes demonstrates that atrophy can be largely described by two components: one overall degenerative component that correlates strongly with different cognitive tests, and one component that mainly captures degeneration of the cortical grey matter that strongly correlates with age. A multimodal correlation analysis indicates that increased brain atrophy and lesion load is accompanied by increased spectral power in the lower alpha (8–10 Hz) in the temporoparietal junction (TPJ). Increased lower alpha power in the TPJ was further associated with worse results on verbal and spatial working memory tests, whereas an increased lower/upper alpha power ratio was associated with slower information processing speed.In conclusion, multiple sclerosis patients with increased brain atrophy, lesion and thalamic volumes demonstrated increased lower alpha power in the TPJ and reduced cognitive abilities.

Functional magnetic resonance imaging (fMRI) allowed the spatial characterization of the resting-state verbal language network (vLN). While other resting-state networks (RSNs) were matched with their electrophysiological equivalents at rest and could be spectrally defined, such correspondence is lacking for the vLN. This magnetoencephalography (MEG) study aimed at defining the spatio-spectral characteristics of the neuromagnetic intrinsic functional architecture of the vLN. Neuromagnetic activity was recorded at rest in 100 right-handed healthy adults (age range: 18–41 years). Band-limited power envelope correlations were performed within and across frequency bands (θ, α, β, and low γ) from a seed region placed in the left Broca’s area, using static orthogonalization as leakage correction. K-means clustering was used to segregate spatio-spectral clusters of resting-state functional connectivity (rsFC). Remarkably, unlike other RSNs, within-frequency long-range rsFC from the left Broca’s area was not driven by one main carrying frequency but was characterized by a specific spatio-spectral pattern segregated along the ventral (predominantly θ and α) and dorsal (β and low-γ bands) vLN streams. In contrast, spatial patterns of cross-frequency vLN functional integration were spectrally more widespread and involved multiple frequency bands. Moreover, the static intrinsic functional architecture of the neuromagnetic human vLN involved clearly left-hemisphere-dominant vLN interactions as well as cross-network interactions with the executive control network and postero-medial nodes of the DMN. Overall, this study highlighted the involvement of multiple modes of within and cross-frequency power envelope couplings at the basis of long-range electrophysiological vLN functional integration. As such, it lays the foundation for future works aimed at understanding the pathophysiology of language-related disorders.

Introduction: Lymph node metastases (LNM) represent a proven prognostic factor for biochemical recurrence (BCR)-free survival, metastatic free survival and overall survival in prostate cancer (PCa). Although pelvic node dissection remains the gold standard for the detection of LNM, novel imaging techniques are entering clinical practice, in the effort to improve LNM detection and spare unnecessary surgeries. Aim of the current review is to describe such imaging techniques and explore their advantages and limitations.Evidence Acquisition: The National Library of Medicine Database was searched for relevant articles published between January 2013 and August 2018. A wide search was performed including the combination of following words: “Prostate” and “Cancer” and “staging” and “Lymph Node” and “imaging” and (“MRI” or “PET”). The initial list of selected papers was enriched by individual suggestions of the authors of the present review.Evidence Synthesis: DWI-MRI in detection of lymph node invasion has a sensitivity and specificity of 41 and 94%, respectively. For SPIO MRI using ferumoxtran-10, the sensitivity for detection of LNM with short axis diameter of 5–10 mm is reported at 96.4%, compared to 28.5% with MRI alone. PSMA PET/CT is growing exponentially, both in the initial detection of LNM and for BCR evaluation. Fluciclovine PET could improve detection of subcentimetric pathologic lymph nodes. Sentinel lymph node techniques remain experimental and not validated in the field of PCa.Conclusions: Molecular imaging, particularly PSMA ligand PET imaging, present interesting diagnostic accuracy in LN diagnosis even in subcentimetric LN. DWI-MRI yields good results in LN involvement evaluation and the use of contrast agent such SPIO may improve the detection rate. The SLN technique is limited to experimental protocols and for intermediate or high-risk PCa. Prospective trials are awaited to evaluate the true clinical impact of these imaging techniques on PCa oncologic outcomes.

Non-invasive imaging and quantification of human beta cell mass remains a major challenge. We performed pre-clinical in vivo validation of a peptide previously discovered by our group, namely, P88 that targets a beta cell specific biomarker, FXYD2γa. We conjugated P88 with DOTA and then complexed it with GdCl3 to obtain the MRI (magnetic resonance imaging) contrast agent (CA) Gd-DOTA-P88. A scrambled peptide was used as a negative control CA, namely Gd-DOTA-Scramble. The CAs were injected in immunodeficient mice implanted with EndoC-βH1 cells, a human beta cell line that expresses FXYD2γa similarly to primary human beta cells. The xenograft-bearing mice were analyzed by MRI. At the end, the mice were euthanized and the CA biodistribution was evaluated on the excised tissues by measuring the Gd concentration with inductively coupled plasma mass spectrometry (ICP-MS). The MRI and biodistribution studies indicated that Gd-DOTA-P88 accumulates in EndoC-βH1 xenografts above the level observed in the background tissue, and that its uptake is significantly higher than that observed for Gd-DOTA-Scramble. In addition, the Gd-DOTA-P88 showed good xenograft-to-muscle and xenograft-to-liver uptake ratios, two potential sites of human islets transplantation. The CA shows good potential for future use to non-invasively image implanted human beta cells.

ABSTRACT: Objective: Insulinoma is the most frequent cause of hyperinsulinemic hypoglycemia in adults, but its preoperative localization may be challenging.Methods: We report on a patient with a remarkably long history of persistent hypoglycemia due to an insulinoma, which was finally localized after 18 years using glucagon-like peptide-1 receptor (GLP-1R) imaging.Results: The patient was admitted in 1995 for hypoglycemia. A fasting test documented inadequate insulin suppression. She had given birth to a baby who was small for gestational age a few weeks earlier. The patient underwent surgery for a pancreatic tail nodule, which histologically proved to be normal tissue. Hypoglycemia recurred postoperatively. Diazoxide initially controlled symptoms, but over the years, the patient had recurrent hypoglycemic seizures and coma. The patient underwent repeated pancreatic magnetic resonance imaging (MRI), indium-111 (111In)-octreotide scintigraphy, galladium-68 (68Ga)-DOTATATE-positron emission tomography (PET) scan, 18F-DOPA-PET scan and arterial calcium stimulation with hepatic venous sampling; all were negative. Finally, a SPECT-CT with indium-111 diethylene triamine pentaacetic acid (111In-DTPA)-exendin-4, a radioligand with high affinity to the GLP-1R, showed focally increased tracer uptake in the pancreas tail. Endoscopic ultrasound (US) and fine-needle aspiration confirmed the endocrine origin of the tumor. The patient underwent laparoscopic tail pancreatectomy and was cured after 18 years of hyper-insulinemic hypoglycemia. Ex vivo studies of the insulinoma confirmed elevated insulin secretion at low glucose concentrations and abundant GLP-1R expression.Conclusion: GLP-1R imaging is a highly valuable tool in the localization of insulinoma when other conventional methods fail to identify the tumor. This new imaging tool will enable timely localization and cure for insulinoma patients.Abbreviations: ASVS selective arterial calcium stimulation and hepatic venous sampling 11C carbon 11 CT computed tomography DTPA diethylene triamine penta-acetic acid 18F-DOPA 18F-3,4-dihydroxyphenylalanine GLP-1R glucagonlike peptide-1 receptor 111In indium-111 KATP channels adenosine triphosphate-sensitive potassium channels MRI magnetic resonance imaging PET positron emission tomography SPECT single-photon-emission computed tomography SST2R somatostatin receptor type 2 SST5R somatostatin receptor type 5 US ultrasound

PURPOSE: Investigating the steadiness of the phase-coupling between the time-course of the reader's voice and brain signals of subjects with autism spectrum disorder (ASD) passively listening to connected speech using magnetoencephalography (MEG). In typically developed subjects, such coupling occurs at the right posterior temporal sulcus (pSTS) for frequencies below 1 Hz, and reflects the neural processing of sentence-level rhythmic prosody at the prelexical level. METHODS: Cortical neuromagnetic signals were recorded with MEG (Elekta Oy, Finland) while seven right-handed and native French-speaking ASD subjects (six males, one female, range: 13-20 years) listened to live (Live) or recorded (Recorded) voices continuously reading a text in French for five minutes. Coherence was computed between the reader's voice time-course and ASD subjects' MEG signals. Coherent neural sources were subsequently reconstructed using a beamformer. KEY FINDINGS: Significant coupling was found at 0.5 Hz in all ASD subjects in Live and in six subjects in Recorded. Coherent sources were located close to the right pSTS in both conditions. No significant difference was found in coherence levels between Live and Recorded, and between ASD subjects and ten typically developed subjects (right-handed, native French-speaking adults, 5 males, 5 females, age range: 21-38 years) included in a previous study. SIGNIFICANCE: This study discloses a preserved coupling between the reader's voice and ASD subjects' cortical activity at the right pSTS. These findings support the existence of preserved neural processing of sentence-level rhythmic prosody in ASD. The preservation of early cortical processing of prosodic elements in verbal language might be exploited in therapeutic interventions in ASD.

PURPOSE: To investigate epilepsy-induced changes in effective connectivity between the non-epileptic amygdalo-hippocampal complex (AHC) and the rest of the brain in patients with unilateral mesiotemporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS). METHODS: Thirty-three patients with unilateral MTLE associated with HS (20 females, mean age: 36 years, 19 left HS) and 33 adult controls matched for age and gender underwent (18)F-Fluorodeoxyglucose positron emission tomography (FDG-PET). Right-HS patients' FDG-PET data were flipped to obtain a left-epileptic-focus-lateralized group of patients. Voxels of interest (VOI) were selected within the cytoarchitectonic probabilistic maps of the non-epileptic AHC (probability level = 100%, SPM8 Anatomy toolbox v1.7). Patients and controls were compared using VOI metabolic activity as covariate of interest to search for epilepsy-induced changes in the contribution of the non-epileptic AHC to the level of metabolic activity in other brain areas. Age, gender, duration of epilepsy, seizure type and frequency were used as covariates of no-interest for connectivity analyses. KEY FINDINGS: Significant decrease in effective connectivity was found between the non-epileptic AHC and ventral prefrontal cortical areas bilaterally, as well as with the temporal pole and the posterior cingulate cortex contralateral to HS. Significant increase in connectivity was found between the non-epileptic AHC and midline structures, such as the anterior cingulate and dorsal medial prefrontal cortices, as well as the temporo-parietal junction bilaterally. Connectivity analyses also revealed a preserved positive connectivity between the non-epileptic and the epileptic AHC in the patients' group. SIGNIFICANCE: This study evidences epilepsy-induced changes in connectivity between the non-epileptic AHC and some limbic and default mode network areas. These changes in connectivity probably account for emotional, cognitive and decision-making impairments frequently observed in MTLE patients. The preserved neurometabolic connectivity between the non-epileptic and the epileptic AHC in MTLE patients is pivotal to explain the epilepsy-induced changes found in this study.

Ankylosing spondylitis is a chronic inflammatory disorder affecting mainly the axial skeleton. Here we report a case of a man with a clinical suspicion of ankylosing spondylitis but with a persistence of increased inflammatory markers. In this case, 18F-FDG-PET/CT revealed multiple hypermetabolic lesions in axial skeleton, lymph nodes, and the lung, suggestive of either disseminated tuberculosis or lymphoma. Histological analysis of the pulmonary lesion revealed mycobacterium tuberculosis. This case highlights, firstly, the importance of excluding other diagnoses in the presence of clinical picture of ankylosing spondylitis and high inflammatory markers and, secondly, the determining role of PET/CT.

Food sharing is vital for a large number of species, either solitary or social, and is of particular importance within highly integrated societies, such as in colonial organisms and in social insects. Nevertheless, the mechanisms that govern the distribution of food inside a complex organizational system remain unknown. Using scintigraphy, a method developed for medical imaging, we were able to describe the dynamics of food-flow inside an ant colony. We monitored the sharing process of a radio-labelled sucrose solution inside a nest of Formica fusca. Our results show that, from the very first load that enters the nest, food present within the colony acts as negative feedback to entering food. After one hour of the experiments, 70% of the final harvest has already entered the nest. The total foraged quantity is almost four times smaller than the expected storage capacity. A finer study of the spatial distribution of food shows that although all ants have been fed rapidly (within 30 minutes), a small area representing on average 8% of the radioactive surface holds more than 25% of the stored food. Even in rather homogeneous nests, we observed a strong concentration of food in few workers. Examining the position of these workers inside the nest, we found heavily loaded ants in the centre of the aggregate. The position of the centre of this high-intensity radioactive surface remained stable for the three consecutive hours of the experiments. We demonstrate that the colony simultaneously managed to rapidly feed all workers (200 ants fed within 30 minutes) and build up food stocks to prevent food shortage, something that occurs rather often in changing environments. Though we expected the colony to forage to its maximum capacity, the flow of food entering the colony is finely tuned to the colony's needs. Indeed the food-flow decreases proportionally to the food that has already been harvested, liberating the work-force for other tasks.