Exploring the mechanism of 18F-fluorodopa uptake in recurrent high-grade gliomas: A comprehensive histomolecular-positron emission tomography analysis.

BACKGROUND: Dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-FDOPA) positron emission tomography (PET) is a valuable tool for managing high-grade gliomas (HGGs), but there is a lack of literature on its relationship with glioma subtypes since the 2021 reclassification of brain tumors. There is also debate surrounding the mechanism of 18F-FDOPA uptake, particularly after chemoradiation therapy. This study aimed to investigate the correlation between 18F-FDOPA uptake and histomolecular characteristics, particularly L-amino acid transporter 1 (LAT1) expression, in recurrent gliomas, and examine their impact on survival in HGGs. METHODS: Thirty-nine patients with recurrent HGGs (14 isocitrate dehydrogenase [IDH]-mutant, 25 IDH-wildtype) who underwent a brain 18F-FDOPA PET/computed tomography (CT) or PET/magnetic resonance imaging (MRI) followed by surgical resection of the 18F-FDOPA-avid lesion within 6 months, were retrospectively reviewed. PET results were compared with histological examination and for SCL7A5/LAT1 immunostaining. The study also examined the relationship between PET parameters, LAT1 expression, and survival outcomes. RESULTS: Astrocytoma IDH-mutant G4 had higher 18F-FDOPA uptake than glioblastoma IDH-wildtype G4 (maximum tumor-to-normal brain ratio [TBRmax] 5 [3.4-9] vs. 3.8 [2.8-5.9], p = 0.02). IDH-mutant gliomas had higher LAT1 expression than IDH-wildtype gliomas (100 [14-273] vs. 15.5 [0-137], p < 0.05) as well as higher TBRmax (5 [2.4-9] vs. 3.8 [2.8-6], p < 0.05). In survival analysis, LAT1 score >100 was a predictor for longer progression-free survival in IDH-mutant HGGs. CONCLUSIONS: To our knowledge, our study is the first to suggest a link between LAT1 expression and IDH mutation status. We showed that higher TBRmax was associated with higher LAT1 expression and IDH mutation status. Further studies are needed to better understand the mechanisms underlying amino acid PET tracers uptake, especially in the post-radiation and chemotherapy settings.

[18F]FDG PET-MRI provides survival biomarkers in primary central nervous system lymphoma in the elderly: an ancillary study from the BLOCAGE trial of the LOC network.

PURPOSE: Primary central nervous system lymphoma (PCNSL) incidence is rising among elderly patients, presenting challenges due to poor prognosis and treatment-related toxicity risks. This study explores the potential of combining [18F]fluorodeoxyglucose ([18F]FDG) PET scans and multimodal MRI for improving management in elderly patients with de novo PCNSL. METHODS: Immunocompetent patients over 60 years with de novo PCNSL were prospectively enrolled in a multicentric study between January 2016 and April 2021. Patients underwent brain [18F]FDG PET-MRI before receiving high-dose methotrexate-based chemotherapy. Relationships between extracted PET (metabolic tumor volume (MTV), sum of MTV for up to five lesions (sumMTV), metabolic imaging lymphoma aggressiveness score (MILAS)) and MRI parameters (tumor contrast-enhancement size, cerebral blood volume (CBV), cerebral blood flow (CBF), apparent diffusion coefficient (ADC)) and treatment response and outcomes were analyzed. RESULTS: Of 54 newly diagnosed diffuse large B-cell PCNSL patients, 52 had positive PET and MRI with highly [18F]FDG-avid and contrast-enhanced disease (SUVmax: 27.7 [22.8-36]). High [18F]FDG uptake and metabolic volume were significantly associated with low ADCmean values and high CBF at baseline. Among patients, 69% achieved an objective response at the end of induction therapy, while 17 were progressive. Higher cerebellar SUVmean and lower sumMTV at diagnosis were significant predictors of complete response: 6.4 [5.7-7.7] vs 5.4 [4.5-6.6] (p = 0.04) and 5.5 [2.1-13.3] vs 15.9 [4.2-19.5] (p = 0.01), respectively. Two-year overall survival (OS) was 71%, with a median progression-free survival (PFS) of 29.6 months and a median follow-up of 37 months. Larger tumor volumes on PET or enhanced T1-weighted MRI were significant predictors of poorer OS, while a high MILAS score at diagnosis was associated with early death (< 1 year). CONCLUSION: Baseline cerebellar metabolism and sumMTV may predict response to end of chemotherapy in PCNSL. Tumor volume and MILAS at baseline are strong prognostic factors.

Added value of [18F]FDOPA PET to the management of high-grade glioma patients after their initial treatment: a prospective multicentre study.

BACKGROUND: Diagnostic value of 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine ([18F]FDOPA) PET in patients with suspected recurrent gliomas is recognised. We conducted a multicentre prospective study to assess its added value in the practical management of patients suspected of recurrence of high grade gliomas (HGG). METHODS: Patients with a proven HGG (WHO grade III and IV) were referred to the multidisciplinary neuro-oncology board (MNOB) during their follow-up after initial standard of care treatment and when MRI findings were not fully conclusive. Each case was discussed in 2 steps. For step 1, a diagnosis and a management proposal were made only based on the clinical and the MRI data. For step 2, the same process was repeated taking the [18F]FDOPA PET results into consideration. A level of confidence for the decisions was assigned to each step. Changes in diagnosis and management induced by [18F]FDOPA PET information were measured. When unchanged, the difference in the confidence of the decisions were assessed. The diagnostic performances of each step were measured. RESULTS: 107 patients underwent a total of 138 MNOB assessments. The proposed diagnosis changed between step 1 and step 2 in 37 cases (26.8%) and the proposed management changed in 31 cases (22.5%). When the management did not change, the confidence in the MNOB final decision was increased in 87 cases (81.3%). Step 1 had a sensitivity, specificity and accuracy of 83%, 58% and 66% and step 2, 86%, 64% and 71% respectively. CONCLUSION: [18F]FDOPA PET adds significant information for the follow-up of HGG patients in clinical practice. When MRI findings are not straightforward, it can change the management for more than 20% of the patients and increases the confidence level of the multidisciplinary board decisions.

Differentiating high-grade glioma progression from treatment-related changes with dynamic [18F]FDOPA PET: a multicentric study.

OBJECTIVES: Diagnostic accuracy of amino-acid PET for distinguishing progression from treatment-related changes (TRC) is currently based on single-center non-homogeneous glioma populations. Our study assesses the diagnostic value of static and dynamic [18F]FDOPA PET acquisitions to differentiate between high-grade glioma (HGG) recurrence and TRC in a large cohort sourced from two independent nuclear medicine centers. METHODS: We retrospectively identified 106 patients with suspected glioma recurrences (WHO GIII, n = 38; GIV, n = 68; IDH-mutant, n = 35, IDH-wildtype, n = 71). Patients underwent dynamic [18F]FDOPA PET/CT (n = 83) or PET/MRI (n = 23), and static tumor-to-background ratios (TBRs), metabolic tumor volumes and dynamic parameters (time to peak and slope) were determined. The final diagnosis was either defined by histopathology or a clinical-radiological follow-up at 6 months. Optimal [18F]FDOPA PET parameter cut-offs were obtained by receiver operating characteristic analysis. Predictive factors and clinical parameters were assessed using univariate and multivariate Cox regression survival analyses. RESULTS: Surgery or the clinical-radiological 6-month follow-up identified 71 progressions and 35 treatment-related changes. TBRmean, with a threshold of 1.8, best-differentiated glioma recurrence/progression from post-treatment changes in the whole population (sensitivity 82%, specificity 71%, p < 0.0001) whereas curve slope was only significantly different in IDH-mutant HGGs (n = 25). In survival analyses, MTV was a clinical independent predictor of progression-free and overall survival on the multivariate analysis (p ≤ 0.01). A curve slope > -0.12/h was an independent predictor for longer PFS in IDH-mutant HGGs CONCLUSION: Our multicentric study confirms the high accuracy of [18F]FDOPA PET to differentiate recurrent malignant gliomas from TRC and emphasizes the diagnostic and prognostic value of dynamic acquisitions for IDH-mutant HGGs. KEY POINTS: • The diagnostic accuracy of dynamic amino-acid PET, for distinguishing progression from treatment-related changes, is currently based on single-center non-homogeneous glioma populations. • This multicentric study confirms the high accuracy of static [18F]FDOPA PET images for differentiating progression from treatment-related changes in a homogeneous population of high-grade gliomas and highlights the diagnostic and prognostic value of dynamic acquisitions for IDH-mutant high-grade gliomas. • Dynamic acquisitions should be performed in IDH-mutant glioma patients to provide valuable information for the differential diagnosis of recurrence and treatment-related changes.

Visual interpretation of brain hypometabolism related to neurological long COVID: a French multicentric experience.

BACKGROUND: This multicentre study aimed to provide a qualitative and consensual description of brain hypometabolism observed through the visual analysis of 18F-FDG PET images of patients with suspected neurological long COVID, regarding the previously reported long-COVID hypometabolic pattern involving hypometabolism in the olfactory bulbs and other limbic/paralimbic regions, as well as in the brainstem and cerebellum. METHODS: From the beginning of August 2021 to the end of October 2021, the brain 18F-FDG PET scans of patients referred for suspected neurological long COVID with positive reverse transcription polymerase chain reaction (RT-PCR) and/or serology tests for SARS-CoV-2 infection were retrospectively reviewed in three French nuclear medicine departments (143 patients; 47.4 years old ± 13.6; 98 women). Experienced nuclear physicians from each department classified brain 18F-FDG PET scans according to the same visual interpretation analysis as being normal, mildly to moderately (or incompletely) affected, or otherwise severely affected within the previously reported long-COVID hypometabolic pattern. RESULTS: On the 143 brain 18F-FDG PET scans performed during this 3-month period, 53% of the scans were visually interpreted as normal, 21% as mildly to moderately or incompletely affected, and 26% as severely affected according to the COVID hypometabolic pattern. On average, PET scans were performed at 10.9 months from symptom onset (± 4.8). Importantly, this specific hypometabolic pattern was similarly identified in the three nuclear medicine departments. Typical illustrative examples are provided to help nuclear physicians interpret long-COVID profiles. CONCLUSION: The proposed PET metabolic pattern is easily identified upon visual interpretation in clinical routine for approximately one half of patients with suspected neurological long COVID, requiring special consideration for frontobasal paramedian regions, the brainstem and the cerebellum, and certainly further adapted follow-up and medical care, while the second half of patients have normal brain PET metabolism on average 10.9 months from symptom onset.

Radiation dose to nuclear medicine technologists when operating PET/MR compared with PET/CT.

Since 2010, positron emission tomography/magnetic resonance (PET/MR) has been increasingly used as clinical routine in nuclear medicine departments. One advantage of PET/MR over PET/computed tomography (CT) is the lower dose of ionising radiation delivered to patients. However, data on the radiation dose delivered to staff operating PET/MR compared with the new generation of PET/CT equipment are still lacking. Our aim was to compare the radiation dose to nuclear medicine technologists performing routine PET/MR and PET/CT in the same department. We retrospectively measured the daily radiation dose received by PET technologists over 13 months by collecting individual dosimetry measurements (from electronic personal dosimeters). Data were analysed taking into account the total number of studies performed with each PET modality (PET/MR with Signa 3T, General Electric Healthcare versus PET/CT with Biograph mCT flow, Siemens), the type of exploration (brain versus whole-body PET), the18F activity injected per day and per patient as well as the time spent in contact with patients after tracer injection. Our results show a significantly higher whole-body exposure to technologists for PET/MR compared with PET/CT (10.3 ± 3.5 nSv versus 4.7 ± 1.2 nSv per18F injected MBq, respectively;p< 0.05). This difference was related to prolonged contact with injected patients during patient positioning with the PET/MR device and MR coil placement, especially in whole-body studies. For an equal injected activity, radiation exposure to PET technologists for PET/MR was twice that of PET/CT. To minimise the radiation dose to staff, efforts should be made to optimise patient positioning, even in departments with extensive PET/CT experience.

Brain 18F-FDG PET for the diagnosis of autoimmune encephalitis: a systematic review and a meta-analysis.

OBJECTIVE: To consolidate current understanding of detection sensitivity of brain 18F-FDG PET scans in the diagnosis of autoimmune encephalitis and to define specific metabolic imaging patterns for the most frequently occurring autoantibodies. METHODS: A systematic and exhaustive search of data available in the literature was performed by querying the PubMed/MEDLINE and Cochrane databases for the search terms: ((PET) OR (positron emission tomography)) AND ((FDG) OR (fluorodeoxyglucose)) AND ((encephalitis) OR (brain inflammation)). Studies had to satisfy the following criteria: (i) include at least ten pediatric or adult patients suspected or diagnosed with autoimmune encephalitis according to the current recommendations, (ii) specifically present 18F-FDG PET and/or morphologic imaging findings. The diagnostic 18F-FDG PET detection sensitivity in autoimmune encephalitis was determined for all cases reported in this systematic review, according to a meta-analysis following the PRISMA method, and selected publication quality was assessed with the QUADAS-2 tool. RESULTS: The search strategy identified 626 articles including references from publications. The detection sensitivity of 18F-FDG PET was 87% (80-92%) based on 21 publications and 444 patients included in the meta-analysis. We also report specific brain 18F-FDG PET imaging patterns for the main encephalitis autoantibody subtypes. CONCLUSION AND RELEVANCE: Brain 18F-FDG PET has a high detection sensitivity and should be included in future diagnostic autoimmune encephalitis recommendations. Specific metabolic 18F-FDG PET patterns corresponding to the main autoimmune encephalitis autoantibody subtypes further enhance the value of this diagnostic.

The cerebral network of COVID-19-related encephalopathy: a longitudinal voxel-based 18F-FDG-PET study.

PURPOSE: Little is known about the neuronal substrates of neuropsychiatric symptoms associated with COVID-19 and their evolution during the course of the disease. We aimed at describing the longitudinal brain metabolic pattern in COVID-19-related encephalopathy using 18F-FDG-PET/CT. METHODS: Seven patients with variable clinical presentations of COVID-19-related encephalopathy were explored thrice with brain 18F-FDG-PET/CT, once in the acute phase, 1 month later and 6 months after COVID-19 onset. PET images were analysed with voxel-wise and regions-of-interest approaches in comparison with 32 healthy controls. RESULTS: Patients' neurological manifestations during acute encephalopathy were heterogeneous. However, all of them presented with predominant cognitive and behavioural frontal disorders. SARS-CoV-2 RT-PCR in the CSF was negative for all patients. MRI revealed no specific abnormalities for most of the subjects. All patients had a consistent pattern of hypometabolism in a widespread cerebral network including the frontal cortex, anterior cingulate, insula and caudate nucleus. Six months after COVID-19 onset, the majority of patients clinically had improved but cognitive and emotional disorders of varying severity remained with attention/executive disabilities and anxio-depressive symptoms, and lasting prefrontal, insular and subcortical 18F-FDG-PET/CT abnormalities. CONCLUSION: The implication of this widespread network could be the neural substrate of clinical features observed in patients with COVID-19, such as frontal lobe syndrome, emotional disturbances and deregulation of respiratory failure perception. This study suggests that this network remains mildly to severely impaired 6 months after disease onset.

Simultaneously acquired PET and ASL imaging biomarkers may be helpful in differentiating progression from pseudo-progression in treated gliomas.

OBJECTIVES: The aim of this work was investigating the methods based on coupling cerebral perfusion (ASL) and amino acid metabolism ([18F]DOPA-PET) measurements to evaluate the diagnostic performance of PET/MRI in glioma follow-up. METHODS: Images were acquired using a 3-T PET/MR system, on a prospective cohort of patients addressed for possible glioma progression. Data were preprocessed with statistical parametric mapping (SPM), including registration on T1-weighted images, spatial and intensity normalization, and tumor segmentation. As index tests, tumor isocontour maps of [18F]DOPA-PET and ASL T-maps were created and metabolic/perfusion abnormalities were evaluated with the asymmetry index z-score. SPM map analysis of significant size clusters and semi-quantitative PET and ASL map evaluation were performed and compared to the gold standard diagnosis. Lastly, ASL and PET topography of significant clusters was compared to that of the initial tumor. RESULTS: Fifty-eight patients with unilateral treated glioma were included (34 progressions and 24 pseudo-progressions). The tumor isocontour maps and T-maps showed the highest specificity (100%) and sensitivity (94.1%) for ASL and [18F]DOPA analysis, respectively. The sensitivity of qualitative SPM maps and semi-quantitative rCBF and rSUV analyses were the highest for glioblastoma. CONCLUSION: Tumor isocontour T-maps and combined analysis of CBF and [18F]DOPA-PET uptake allow achieving high diagnostic performance in differentiating between progression and pseudo-progression in treated gliomas. The sensitivity is particularly high for glioblastomas. KEY POINTS: • Applied separately, MRI and PET imaging modalities may be insufficient to characterize the brain glioma post-therapeutic profile. • Combined ASL and [18F]DOPA-PET map analysis allows differentiating between tumor progression and pseudo-progression.

Habituation of auditory startle reflex is a new sign of minimally conscious state.

Neurological examination of non-communicating patients relies on a few decisive items that enable the crucial distinction between vegetative state (VS)-also coined unresponsive wakefulness syndrome (UWS)-and minimally conscious state. Over the past 10 years, this distinction has proven its diagnostic value as well as its important prognostic value on consciousness recovery. However, clinicians are currently limited by three factors: (i) the current behavioural repertoire of minimally conscious state items is limited and restricted to a few cognitive domains in the goldstandard revised version of the Coma Recovery Scale; (ii) a proportion of ∼15-20% clinically VS/UWS patients are actually in a richer state than VS/UWS as evidenced by functional brain imaging; and (iii) the neurophysiological and cognitive interpretation of each minimally conscious state item is still unclear and debated. In the current study we demonstrate that habituation of the auditory startle reflex (hASR) tested at bedside constitutes a novel, simple and powerful behavioural sign that can accurately distinguish minimally conscious state from VS/UWS. In addition to enlarging the minimally conscious state items repertoire, and therefore decreasing the low sensitivity of current behavioural measures, we also provide an original and rigorous description of the neurophysiological basis of hASR through a combination of functional (high density EEG and 18F-fluorodeoxyglucose PET imaging) and structural (diffusion tensor imaging MRI) measures. We show that preservation of hASR is associated with the functional and structural integrity of a brain-scale fronto-parietal network, including prefrontal regions related to control of action and inhibition, and meso-parietal areas associated with minimally conscious and conscious states. Lastly, we show that hASR predicts 6-month improvement of consciousness. Taken together, our results show that hASR is a cortically-mediated behaviour, and suggest that it could be a new clinical item to clearly and accurately identify non-communicating patients who are in the minimally conscious state.

Use of FDG-PET/CT for systemic assessment of suspected primary central nervous system lymphoma: a LOC study.

INTRODUCTION: Primary Central Nervous System Lymphoma (PCNSL) is a rare disease with different therapeutic implications than systemic lymphoma. In this study, we evaluated whole-body 18FDG-PET/CT for pre-chemotherapy imaging of suspected PCNSL. METHODS: One hundred and thirty consecutive immunocompetent patients were retrospectively included. The results of initial 18FDG-PET/CT, contrast-enhanced CT (CeCT) and bone marrow biopsy (BMB) when available were compared to a gold standard based on pathological diagnosis or follow-up. RESULTS: CNS lesion pathology showed large B-cell lymphoma in 95% of patients, including 11 patients with primary vitro-retinal lymphoma. Ten patients (8%) where ultimately diagnosed with systemic lymphoma involvement, including five pathologically confirmed cases, all of which were detected by 18FDG-PET/CT. 18FDG-PET/CT showed incidental systemic findings unrelated to lymphoma in 14% of patients. An SUVmax threshold of nine enabled good discrimination between systemic lymphoma and other lesions (sensitivity 92% and specificity 89%). CeCT and BMB performed in 108 and 77 patients respectively revealed systemic lesions in only three patients. CONCLUSION: 18FDG-PET/CT detected concomitant occult systemic involvement in a non-negligible proportion of suspected PCNSL cases (8%). In this setting its sensitivity is higher than that of CeCT. All of our patients ultimately diagnosed with concomitant systemic involvement had positive 18FDG-PET/CT. We believe it constitutes a safe one-stop shop evaluation for the systemic pre-treatment imaging of suspected PCNSL.

ZTE MR-based attenuation correction in brain FDG-PET/MR: performance in patients with cognitive impairment.

OBJECTIVE: One of the main challenges of integrated PET/MR is to achieve an accurate PET attenuation correction (AC), especially in brain acquisition. Here, we evaluated an AC method based on zero echo time (ZTE) MRI, comparing it with the single-atlas AC method and CT-based AC, set as reference. METHODS: Fifty patients (70 ± 11 years old, 28 men) underwent FDG-PET/MR examination (SIGNA PET/MR 3.0 T, GE Healthcare) as part of the investigation of suspected dementia. They all had brain computed tomography (CT), 2-point LAVA-flex MRI (for atlas-based AC), and ZTE-MRI. Two AC methods were compared with CT-based AC (CTAC): one based on a single atlas, one based on ZTE segmentation. Impact on brain metabolism was evaluated using voxel and volumes of interest-based analyses. The impact of AC was also evaluated through comparisons between two subgroups of patients extracted from the whole population: 15 patients with mild cognitive impairment and normal metabolic pattern, and 22 others with metabolic pattern suggestive of Alzheimer disease, using SPM12 software. RESULTS: ZTE-AC yielded a lower bias (3.6 ± 3.2%) than the atlas method (4.5 ± 6.1%) and lowest interindividual (4.6% versus 6.8%) and inter-regional (1.4% versus 2.6%) variabilities. Atlas-AC resulted in metabolism overestimation in cortical regions near the vertex and cerebellum underestimation. ZTE-AC yielded a moderate metabolic underestimation mainly in the occipital cortex and cerebellum. Voxel-wise comparison between the two subgroups of patients showed that significant difference clusters had a slightly smaller size but similar locations with PET images corrected with ZTE-AC compared with those corrected with CT, whereas atlas-AC images showed a notable reduction of significant voxels. CONCLUSION: ZTE-AC performed better than atlas-AC in detecting pathologic areas in suspected neurodegenerative dementia. KEY POINTS: • The ZTE-based AC improved the accuracy of the metabolism quantification in PET compared with the atlas-AC method. • The overall uptake bias was 21% lower when using ZTE-based AC compared with the atlas-AC method. • ZTE-AC performed better than atlas-AC in detecting pathologic areas in suspected neurodegenerative dementia.

Radiation dose of nuclear medicine technicians performing PET/MR.

Since october 2015, PET/MR has been used extensively for clinical routine in the nuclear medicine department of the Pitié-Salpêtrière Hospital (Paris, France) with a throughput of 11 to 15 patients each day. While many studies have been conducted to investigate dose reduction strategies to patients with hybrid PET/MR devices, no study has focused on staff radiation safety. Knowing that patient positioning within the scanner takes longer in PET/MR than in PET/CT because of the placement of several local MR receive coils, a retrospective study was carried out to measure the radiation doses to nuclear medicine technologists from the patient. The analysis was conducted during one year on 1332 clinical PET/MR studies performed with the Signa PET/MR system (General Electric Healthcare) in our department. The whole-body exposure of the technologist staff was on average for all PET/MR exams10.3 ± 4 nSv per injected MBq of 18 F. When performing brain PET/MR exams only, the whole-body exposure was on average 8.7 ± 2 nSv per injected MBq of 18 F. Brain PET/MR provides lower radiation dose than whole-body examinations for cancer screening due to a lower injected activity (2 vs. 3 MBq kg-1) and shorter patient positioning (5 vs. 15 min). When starting PET/MR in a nuclear medicine department, an important step is to optimise patient positionning within the scanner to minimise radiation dose received by the technical staff from patients.

Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects.

PURPOSE: [18F]MK6240 was developed for PET imaging of tau aggregates, which are implicated in Alzheimer's disease. The goal of this work was to evaluate the kinetics of [18F]MK6240 and to investigate different strategies for in-vivo quantification of tau aggregates in humans. METHODS: Thirty-five subjects, consisting of 18 healthy controls (CTRL), 11 subjects with mild cognitive impairment (MCI) and six with Alzheimer's Disease (AD), underwent dynamic [18F]MK6240 PET scans. Arterial blood measurements were collected in 16 subjects (eight CTRLs, six MCIs and two AD) to measure whole blood and plasma concentration time courses. Radiometabolite analysis was performed on a subset of plasma samples. Various compartmental model configurations as well as the Logan and multilinear analysis (MA1) graphical methods with arterial plasma input function were tested. Simplified reference tissue methods were investigated, including Logan distribution volume ratio (DVR), multilinear reference tissue method (MRTM2), and static SUV ratio using the cerebellum as a reference region. RESULTS: Whole blood:plasma ratio stabilized to 0.66 ± 0.01 after 15 min. Percent parent in plasma (%PP) followed a single exponential and ranged from 0 to 10% at 90 min. [18F]MK6240 in gray matter peaked quickly (SUV > 2 at ~3 min). The preferred compartmental model was a reversible two-tissue compartment model, with the blood contribution included as a model parameter (2T4k1v). Compartmental and graphical analysis methods with arterial input functions yielded concordant results, but rapid metabolism raised challenges for blood-based quantification. MCI and AD subjects demonstrated a broad range of VT as compared to CTRL subjects. DVR from MRTM2 and Logan reference tissue methods correlated with DVR calculated indirectly from compartmental modeling, but underestimation was observed in data sets with very high binding (DVR > 3). SUVR also underestimated indirect DVR from blood-based analyses in high binding regions, although a non-linear relationship was exhibited. CONCLUSIONS: [18F]MK6240 exhibited a wide dynamic range of uptake, with binding patterns in MCI/AD subjects consistent with neurofibrillary tau deposition patterns. Linearized reference tissue methods using an estimated average tissue-to-plasma efflux constant [Formula: see text] and static SUVR agreed well with blood-based methods for most data sets; however, discrepancies were noted in the highest binding cases. Caution should therefore be exercised in application of simplified methods to such data sets, and in quantitative interpretation of corresponding outcomes.

Dopaminergic denervation using [123I]-FPCIT and pain in Parkinson's disease: a correlation study.

In patients with Parkinson's disease (PD), abnormal activations of nociceptive brain areas and lowered pain thresholds were reported, probably reflecting a central modification of pain processing. The aim of this study was to investigate the possible correlation between the striatal and extrastriatal dopaminergic system and pain threshold in PD patients. We included 25 PD patients with various intensities of central pain (visual analog scale). Subjective pain threshold (thermotest) and a motor examination (UPDRS III) were performed. Patients underwent SPECT imaging with [123I]-FP-CIT. We analyzed the correlation between [123I]-FP-CIT binding and subjective pain threshold, using a simple linear regression model for striatal uptake and a voxel-based approach for extrastriatal uptake. The covariables were age, sex, duration of PD, and UPDRS motor score. A pain matrix mask was also used to identify clusters in relation with pain matrix. Striatal analysis revealed that [123I]-FP-CIT binding was negatively correlated with age (p = 0.02), duration of PD (p = 0.0002) and UPDRS motor score (p = 0.006), but no correlation with pain threshold was observed. The extrastriatal analysis showed a positive correlation between [123I]-FP-CIT binding and subjective heat pain threshold for the left posterior cingulate cortex (PCC) (p < 0.001) and negative correlations for the right secondary visual cortex (p < 0.001) and left insula (p < 0.001). When applying the pain matrix mask, correlations remained significant only in the left PCC and the left insula. We suggest that pain perception abnormalities in PD are not directly related to striatal dopaminergic dysfunction. Painful sensations may be related to extrastriatal monoaminergic systems.

18F-Fluorocholine PET/CT and Parathyroid 4D Computed Tomography for Primary Hyperparathyroidism: The Challenge of Reoperative Patients.

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.

A New Fire Hazard for MR Imaging Systems: Blankets-Case Report.

In this report, a case of fire in a positron emission tomography (PET)/magnetic resonance (MR) imaging system due to blanket combustion is discussed. Manufacturing companies routinely use copper fibers for blanket fabrication, and these fibers may remain within the blanket hem. By folding a blanket with these copper fibers within an MR imaging system, one can create an electrical current loop with a major risk of local excessive heating, burn injury, and fire. This hazard applies to all MR imaging systems. Hybrid PET/MR imaging systems may be particularly vulnerable to this situation, because blankets are commonly used for fluorodeoxyglucose PET to maintain a normal body temperature and to avoid fluorodeoxyglucose uptake in brown adipose tissue. © RSNA, 2017.

Cortical areas involved in behavioral expression of external pallidum dysfunctions: A PET imaging study in non-human primates.

The external pallidum (GPe) is a component of the indirect pathway centrally placed in the basal ganglia. Studies already demonstrated that the pharmacological disinhibition of the sensorimotor, associative, and limbic GPe produced dyskinesia, hyperactivity, and compulsive behaviors, respectively. The aim of this study was to investigate the cortical regions altered by the disinhibition of each GPe functional territory. Thus, 5 macaques were injected with bicuculline in sensorimotor, associative, and limbic sites of the GPe producing dyskinesia, hyperactivity, and compulsive behaviors, and underwent in vivo positron tomography with 18F-2-fluoro-2-deoxy-D-glucose to identify cortical dysfunctions related to GPe disinhibition. Blood cortisol levels were also quantified as a biomarker of anxiety for each condition. Our results showed that pallidal bicuculline injections in anesthetized animals reproducibly modified the activity of specific ipsilateral and contralateral cortical areas depending on the pallidal territory targeted. Bicuculline injections in the limbic GPe led to increased ipsilateral activations in limbic cortical regions (anterior insula, amygdala, and hippocampus). Injections in the associative vs. sensorimotor GPe increased the activity in the ipsilateral midcingulate vs. somatosensory and parietal cortices. Moreover, bicuculline injections increased blood cortisol levels only in animals injected in their limbic GPe. These are the first functional results supporting the model of opened cortico-striato-thalamo-cortical loops where modifications in a functional pallidal territory can impact cortical activities of the same functional territory but also cortical activities of other functional territories. This highlights the importance of the GPe as a crucial node in the top-down control of the cortico-striato-thalamo-cortical circuits from the frontal cortex to influence the perception, attention, and emotional processes at downstream (or non-frontal) cortical levels. Finally, we showed the implication of the ventral pallidum with the amygdala and the insular cortex in a circuit related to aversive processing that should be crucial for the production of anxious disorders.

Direct current stimulation over the anterior temporal areas boosts semantic processing in primary progressive aphasia.

OBJECTIVE: Noninvasive brain stimulation in primary progressive aphasia (PPA) is a promising approach. Yet, applied to single cases or insufficiently controlled small-cohort studies, it has not clarified its therapeutic value. We here address the effectiveness of transcranial direct current stimulation (tDCS) on the semantic PPA variant (sv-PPA), applying a rigorous study design to a large, homogeneous sv-PPA cohort. METHODS: Using a double-blind, sham-controlled counterbalanced cross-over design, we applied three tDCS conditions targeting the temporal poles of 12 sv-PPA patients. Efficiency was assessed by a semantic matching task orthogonally manipulating "living"/"nonliving" categories and verbal/visual modalities. Conforming to predominantly left-lateralized damage in sv-PPA and accounts of interhemispheric inhibition, we applied left hemisphere anodal-excitatory and right hemisphere cathodal-inhibitory tDCS, compared to sham stimulation. RESULTS: Prestimulation data, compared to 15 healthy controls, showed that patients had semantic disorders predominating with living categories in the verbal modality. Stimulation selectively impacted these most impaired domains: Left-excitatory and right-inhibitory tDCS improved semantic accuracy in verbal modality, and right-inhibitory tDCS improved processing speed with living categories and accuracy and processing speed in the combined verbal × living condition. INTERPRETATION: Our findings demonstrate the efficiency of tDCS in sv-PPA by generating highly specific intrasemantic effects. They provide "proof of concept" for future applications of tDCS in therapeutic multiday regimes, potentially driving sustained improvement of semantic processing. Our data also support the hotly debated existence of a left temporal-pole network for verbal semantics selectively modulated through both left-excitatory and right-inhibitory brain stimulation. Ann Neurol 2016;80:693-707.