Positron Emission Tomography MRI Research Articles

Probing Estrogen Sulfotransferase-Mediated Inflammation with [11C]-PiB in the Living Human Brain.

2-(4'- [11C]Methylaminophenyl)-6-hydroxybenzothiazole ([11C]-PiB), purportedly a specific imaging agent for cerebral amyloid-β plaques, is a specific, high affinity substrate for estrogen sulfotransferase (SULT1E1), an enzyme that regulates estrogen homeostasis. In this work, we use positron emission tomography (PET) imaging with [11C]-PiB to assess the functional activity of SULT1E1 in the brain of moyamoya disease patients. Ten moyamoya subjects and five control patients were evaluated with [11C]-PiB PET and structural MRI scans. Additionally, a patient with relapsing-remitting multiple sclerosis (RRMS) received [11C]-PiB PET scans before and after steroidal and immunomodulatory therapy. Parametric PET images were established to assess SULT1E1 distribution in the inflamed brain tissue. Increased [11C]-PiB SRTM DVR in the thalamus, pons, corona radiata, and internal capsule of moyamoya cohort subjects was observed in comparison with controls (p ≤ 0.01). This was observed in patients without treatment, with collateralization, and also after radiation. The post-treatment [11C]-PiB PET scan in one RRMS patient also revealed substantially reduced subcortical brain inflammation. In validation studies, [11C]-PiB autoradiography signal in the peri-infarct area of the rat middle cerebral arterial occlusion stroke model was shown to correlate with SULT1E1 immunohistochemistry. Strong [11C]-PiB PET signal associated with intracranial inflammation in the moyamoya syndrome cohort and a single RRMS patient appears consistent with functional imaging of SULT1E1 activity in the human brain. This preliminary work offers substantial and direct evidence that significant [11C]-PiB PET focal signals can be obtained from the living human brain with intracranial inflammation, signals not attributable to amyloid-β plaques.

The impact of 18F-FDG PET on initial staging and therapy planning of pediatric soft-tissue sarcoma patients.

Soft-tissue sarcomas in children are a histologically heterogenous group of malignant tumors accounting for approximately 7% of childhood cancers. There is a paucity of data on the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for initial staging and whether PET influenced management of these patients. The aim of this analysis is to assess the use of 18F-FDG PET exclusively, and as a supplement to cross-sectional imaging in comparison to typical imaging protocols (CT and magnetic resonance imaging [MRI]) for initial staging as well as therapy planning in pediatric soft-tissue sarcoma patients. The list of 18F-FDG PET/CT performed for soft-tissue sarcoma between March 2007 and October 2017 was obtained from the Hospital Information System database. Twenty-six patients who had received 18F-FDG PET, MRI and/or CT at initial diagnosis were included in the study. 18F-FDG PET and concurrent diagnostic CT and MRI at initial staging were independently reviewed to note the number of primary and metastatic lesions detected by each modality. A chart review was conducted to collect information on final diagnosis, staging and treatment plan. During the study period, 26 patients (15 females) ages 1.3-17.9years (median age: 6years) had received 18F-FDG PET/CT at initial diagnosis of soft-tissue sarcoma. Diagnostic CT was available for comparison in all 26 patients and MRI was available in 18 patients. The mean interval between cross-sectional imaging and 18F-FDG PET was 5.9days (range: 0-30days). All 26 primary lesions were equally detected by 18F-FDG PET compared to CT and MRI. From 84 metastatic lesions, 16 were detected by PET as well as CT and MRI, 12 by 18F-FDG PET only (included mainly lymph node metastases) and 56 by CT and MRI only (included mainly lung metastases). 18F-FDG PET changed therapy planning in 5 patients out of 26 (19%) by showing additional lesions not detected by CT and MRI. 18F-FDG PET proved to be a valuable tool for precise initial staging of pediatric soft-tissue sarcoma patients, especially in detecting lymph node metastasis, and could be included in their initial work-up. Given the relative rarity and heterogeneity of this group of tumors, additional investigations are required to definitely establish a role for 18F-FDG PET in the initial staging and therapy planning of soft-tissue sarcoma in the pediatric population.

Detectability of Malignant Lesions by Whole-Body Magnetic Resonance Imaging Using Whole-Body Integrated Positron Emission Tomography/Magnetic Resonance Imaging.

To assess the diagnostic ability of whole-body magnetic resonance imaging (MRI) using integrated positron emission tomography/MRI(PET/MRI). Axial T2-weighted image (T2WI), diffusion-weighted imaging (DWI), coronal T1-weighted image (T1WI), axial volumetric interpolated breath-hold examination in the lung field, and 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG-PET) were evaluated in combination with T2WI alone, T2WI + DWI, T2WI + DWI + T1WI, T2WI + DWI + T1WI + volumetric interpolated breath-hold examination (all MRI images), and all MRI + FDG-PET. A total of 370 lesions were observed in 90 (62.5%) of the 144 patients. The lesion-based sensitivities were 62%, 74%, 74%, 76%, and 94%, and the patient-based sensitivities were 70%, 77%, 77%, 77%, and 81% using T2WI, T2WI + DWI, T2WI + DWI + T1WI, all MRI, and all MRI + FDG-PET, respectively. There were significant differences in the lesion-based sensitivity between T2WI and other sequence combinations and between all MRI and all MRI + FDG-PET. No significant differences were observed between any combinations among the patient-based sensitivities. The sensitivity of whole-body MRI was lower when lesion based, but almost equivalent when patient based compared with PET/MRI.

Evidence of diffuse cerebellar neuroinflammation in multiple sclerosis by 11C-PBR28 MR-PET

Background: Activated microglia, which can be detected in vivo by 11C-PBR28 positron emission tomography (PET), represent a main component of MS pathology in the brain. Their role in the cerebellum is still unexplored, although cerebellar involvement in MS is frequent and accounts for disability progression. Objectives: We aimed at characterizing cerebellar neuroinflammation in MS patients compared to healthy subjects by combining 11C-PBR28 MRI-Positron Emission Tomography (MR-PET) with 7 Tesla (T) MRI and assessing its relationship with brain neuroinflammation and clinical outcome measures. Methods: Twenty-eight MS patients and 16 healthy controls underwent 11C-PBR28 MR-PET to measure microglia activation in normal appearing cerebellum and lesions segmented from 7 T scans. Patients were evaluated using the Expanded Disability Status Scale and Symbol Digit Modalities Test. 11C-PBR28 binding was assessed in regions of interest using 60–90 minutes standardized uptake values normalized by a pseudo-reference region in the brain normal appearing white matter. Multilinear regression was used to compare tracer uptake in MS and healthy controls and assess correlations with clinical scores. Results: In all cerebellar regions examined, MS patients showed abnormally increased tracer uptake, which correlated with cognitive and neurological disability. Conclusion: Neuroinflammation is widespread in the cerebellum of patients with MS and related to neurological disability and cognitive impairment.

Visualization of Inflammation After Cryoballoon Ablation in Atrial Fibrillation Patients - Protocol for Proof-of-Concept Feasibility Trial.

Background: Atrial fibrosis and inflammation play important roles in perpetuating and initiating atrial fibrillation (AF). Although the fibrotic area can be visualized as a delayed enhancement area on late gadolinium enhancement magnetic resonance imaging (LGE-MRI), atrial inflammation has not yet been visualized on any imaging modality. We describe the protocol for a feasibility study to visualize atrial inflammation on positron emission tomography/MRI (PET/MRI). Methods and Results: This is a single-arm, prospective, open-label proof-of concept trial, involving AF patients after cryoballoon ablation (CBA). A total of 30 paroxysmal AF patients will be enrolled and undergo simultaneous PET/MRI for the assessment of regional 18F-fluorodeoxyglucose (18F-FDG) uptake 1 day after the CBA. Furthermore, LGE-MRI will be performed before CBA, and at 1 and 4 weeks after assessing the regional LGE area. The main outcome measures will be (1) the feasibility of imaging inflammation in the left atrium on PET/MRI; and (2) the safety of the intervention. Conclusions: There are few data on the visualization of atrial inflammation using PET/MRI. Establishing the visualization methodology will contribute to elucidating the fundamental histopathologic findings of the progress to fibrosis, and to the planning and execution of a larger definitive trial to test the usefulness of PET/MRI.

Combination bone marrow imaging using positron emission tomography (PET)-MRI in plasma cell dyscrasias: correlation with prognostic laboratory values and clinicopathological diagnosis.

Objective:This prospective observational study of positron emission tomography (PET)-MRI findings in 16 consecutive newly diagnosed patients with a plasma cell dyscrasia describes and compares MRI-detected myeloma lesions with 18F-fludeoxyglucose PET-avid myeloma lesions, and correlates quantitative imaging findings to a range of biochemical and prognostic parameters.Methods:Simultaneously acquired whole body PET and MRI images were evaluated qualitatively for the presence of focal or generalised abnormalities of bone marrow (BM) on either modality. Quantitative analysis comprised mean standardised uptake values (SUVmean) and fractional water content of the BM measured from PET and chemical shift MRI images of the second to fourth lumbar vertebrae.Results:Final diagnoses comprised symptomatic myeloma (n = 10), asymptomatic myeloma (n = 4) and monoclonal gammopathy of uncertain significance (n = 2). 8/10 patients with symptomatic myeloma demonstrated BM abnormalities on qualitative assessment of MRI compared to 4/10 on PET. BM SUVmean inversely correlated with serum albumin (r = 0.57, p = 0.017). BM water fraction correlated with trephine cellularity and blood platelet count (r = 0.78, p = 0.00039 and r = 0.61, p = 0.0013 respectively). BM water fraction correlated with SUVmean in patients with low plasma cell burden (r = 0.91, p = 0.0015) but not in patients with high plasma cell burden (r = 0.18, p = 0.61).Conclusion:PET-MRI shows promise in both morphological and functional multiparametric quantitative assessment of myeloma.Advances in knowledge:For the first time, multiparametric imaging in myeloma has been shown to predict BM abnormalities and correlate with known biochemical prognostic markers, moving PET-MRI beyond simple diagnostic applications into potential prognostic and treatment selection applications.

Quantitative volumetric analysis of primary glioblastoma multiforme on MRI and 11C-methionine PET: initial study on five patients.

To investigate the discrepancy between 11C-methionine (MET) positron emission tomography (PET) and MRI results in primary glioblastoma multiforme (GBM) through three-dimensional (3D) volumetric analysis, we retrospectively analysed patients with primary GBM who underwent preoperative 3D MRI and MET PET and were operated between June 2016 and January 2017. Tumour delineation and volumetric analysis were conducted using MRIcron software. Tumour volumes defined by MRI (VMRI) were manually drawn slice by slice in axial and sagittal or coronal images of enhanced T1 sequence, while metabolic tumour volumes were automatically segmented in MET PET (VMET) based on three (frontal, occipital and temporal) 3D reference volumes of interest (VOI). Discrepancies were evaluated in terms of both absolute volume and percentage on the combined images. MET PET contours contained and extended beyond MRI contours in all five patients; in a subset of cases, MET PET contours extended to the contralateral hemisphere. The discrepancy between MET uptake and MRI results was 27.67 cm3 (4.20-51.20 cm3), i.e. approximately 39.0% (17.4-64.3%) of the metabolic tumour volume was located outside the volumes of the Gd-enhanced area. Metabolic tumour volume is substantially underestimated by Gd-enhanced area in patients with primary GBM. Quantitative volumetric information derived from MET uptake is useful in defining tumour targets and designing individualised therapy strategies in primary GBM.

Relationship between 18F-FDG PET metabolic parameters and MRI intravoxel incoherent motion (IVIM) histogram parameters and their correlations with clinicopathological features of cervical cancer: evidence from integrated PET/MRI

To explore the relationship between positron-emission tomography (PET) and intravoxel incoherent motion (IVIM) histogram parameters and their correlations with the clinicopathological features of cervical squamous cell cancer (CSCC). Forty-four patients with CSCC underwent pelvic combined PET/magnetic resonance imaging (MRI) including IVIM sequences. The maximum/mean standardized uptake value (SUVmax/SUVmean), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) of PET, histogram parameters of apparent diffusion coefficient (ADC), IVIM biomarkers of tissue diffusivity (D), and perfusion fraction (F) were calculated. Correlations between SUV and IVIM (including ADC) histogram parameters, imaging parameters and clinicopathological features were evaluated. SUV showed weak or no correlations with most histogram parameters of ADC, D, and F, except for a moderate correlation between SUVmax or SUVmean and ADCmin (r=-0.69, p<0.001; r=-0.66, p=0.005). MTV, TLG were significantly higher (p<0.05) in tumours with larger diameters, advanced stages, and higher squamous cell carcinoma antigen (SCC-ag). SkewnessADC, kurtosisADC, entropyADC, and kurtosisD for tumour diameters, skewnessF and kurtosisF for tumour stages, kurtosisADC and entropyADC for SCC-ag were statistically significant (p<0.05). MTV (p=0.003), TLG (p=0.004), P10ADC (p=0.001), P25ADC (p=0.021), P10D (p<0.001) and P75F (p=0.014) were significantly different between G1/2 and G3 tumours. The receiver operating characteristic (ROC) curve indicated that P10D had the largest area under curve (AUC=0.868). No universal correlations between SUV and IVIM parameters were found in this study, and further investigation of PET and IVIM parameters as independent potential biomarkers should be investigated for evaluating the clinicopathological characteristics of cervical cancer.

Association of deposition of tau and amyloid-β proteins with structural connectivity changes in cognitively normal older adults and Alzheimer's disease spectrum patients.

IntroductionAlzheimer's disease (AD) is characterized by accumulation of extracellular amyloid‐β and intracellular tau neurofibrillary tangles. The recent advent of tau positron emission tomography (PET) has enabled in vivo assessment of tau pathology. The aim of this study was to explore whether tau deposition influences the structural connectivity in amyloid‐negative and amyloid‐positive groups, and further explore the difference between the groups.MethodsWe investigated 18 patients with amnestic mild cognitive impairment/mild AD (AD‐spectrum group) and 35 cognitively normal older adults (CN group) using diffusion MRI, amyloid, and tau PET imaging. Diffusion connectometry was performed to identify white matter pathways correlated with each of the six variables of tau deposition in the bilateral hippocampi, temporal lobes, posterior and anterior cingulate cortices, precunei, orbitofrontal lobes, and entire cerebrum.ResultsThe CN group showed increased connectivity along with an increased tau deposition in the bilateral hippocampi, temporal lobes, and entire cerebrum, whereas the AD‐spectrum group showed decreased connectivity in the bilateral hippocampi, temporal lobes, anterior and posterior cingulate cortices, precunei, and entire cerebrum.ConclusionThese findings suggest that tau deposition in the CN group seems to induce a compensatory response against early neuronal injury or chronic inflammation associated with normal aging, whereas the coexistence of amyloid and tau in the AD‐spectrum group seems to outweigh the compensatory response leading to decreased connectivity, suggesting that amyloid plays a crucial role in alternating structural connectivity.

Altered connectivity between striatal and extrastriatal regions in patients with schizophrenia on maintenance antipsychotics: an [18 F]fallypride PET and functional MRI study.

In addition to probing regional differences in receptor availability, molecular positron emission tomography (PET) is proving useful for investigating perturbations in neurotransmitter networks using interregional correlation analyses. In a multi-modal imaging study, we examined interregional correlationsof dopamine D2/3 receptor availability between striatal and extrastriatal regions using [18 F]fallypride high-resolution PET in 11 patients with schizophrenia receiving low-dose maintenance atypical antipsychotics and 14 healthy control subjects, and investigated resting-state functional connectivity in the same subjects using seed-based functional magnetic resonance imaging (fMRI) analysis. In the healthy control group, there were no significant correlations of [18 F]fallypride binding potential (BPND ) between striatal regions and any cortical areas, whereas the patient group showed significant and widespread inter-correlations. Correlations between BPND in striatum, amygdala and insula with cortex were significantly higher in patients than in controls. In seed-based resting-state fMRI analysis, the healthy controls revealed positive and negative functional connectivity patterns, while patients exhibited a pattern of exclusively positive connectivity. Functional connectivity was significantly higher between striatal regions and extrastriatal areas including cortical regions in patients compared to controls. In this first such report, molecular and functional connectivity between striatal and extrastriatal regions was primarily characterized by increased interregional relationships in treated patients with schizophrenia. The results suggest that the spatial organization of D2/3 receptor availability and related functional connectivity are significantly perturbed in stable outpatients on maintenance antipsychotics. Future studies should include antipsychotic-naïve patients to determine if these relationships are illness-related characteristics, or arising due to chronic antipsychotic treatment.

68Ga-PSMA-PET: added value and future applications in comparison to the current use of choline-PET and mpMRI in the workup of prostate cancer.

Positron emission tomography (PET) has been commonly and successfully used, in combination with computed tomography (CT) and more recently magnetic resonance (MRI), in the workup of intermediate or high-risk prostate cancer (PCa). Nowadays, new specific receptor targeted PET tracers in prostate cancer imaging have been introduced; one of the most used is 68Ga-PSMA, that evaluates the expression of prostate-specific membrane antigen (PSMA). This tracer has been rapidly taken into account for its better sensitivity and specificity compared to lipid metabolism tracers, such as 11C/18F labelled fluorocholine. Besides, in the era of theranostics, this tracer is having a useful application not only for imaging but also for therapeutic purposes. The aim of this review article is, in the first part, to give an overview of the main indications and future development of 68Ga-PSMA imaging, using PET/CT or PET/MRI, according to the clinical course of the disease and in view of the current use of multiparametric MRI (mpMRI) and choline PET in the management of PCa. In the second part, a brief overview of the promising 18F-labelled PSMA tracers and the current use of PSMA radionuclide therapy will be provided.

Comparison of time curves from dynamic 18F-fluciclovine positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging for primary prostate carcinomas.

Multimodal imaging is increasingly included in the assessment of prostate cancer patients, and there is a need to study whether different techniques provide similar or complementary information. In the initial perfusion phase contrast agents and radioactive labelled tracers act as blood-pool agents and may show similar characteristics. The purpose of the current work was to compare time-activity- and time-concentration-curves (TCs) of dynamic 18F-fluciclovine (18F-anti-1-amino-2-[F]-fluorocyclobutane-1-carboxylic acid, FACBC) positron emission tomography (PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). Dynamic FACBC PET and DCE MRI were performed on 22 patients with intermediate or high-risk prostate cancer within 23 days prior to robot-assisted laparoscopic prostatectomy. Index tumour was delineated in the images using whole mount tissue sections as reference standard. Tumour TCs from PET and MRI were compared visually and quantitatively by calculating correlation coefficients between the curves at different time points after injection. For the first minute post injection, the mean correlation coefficient between the TCs from PET and MRI was 0.92 (range; 0.75-0.99). After the first minute, MRI showed washout while PET showed plateau kinetics. Dynamic FACBC and DCE MRI showed similar wash-in time curve characteristics. At later time points, FACBC plateaued whereas MR contrast medium washed out. In DCE MRI, the usefulness of wash-in information is well documented. Whether wash-in information from dynamic FACBC can provide added value remains to be documented.

Associations Between Histogram Analysis DCE MRI Parameters and Complex 18F-FDG-PET Values in Head and Neck Squamous Cell Carcinoma.

To analyze associations between parameters of positron-emission tomography (PET) and histogram analysis values of dynamic contrast-enhanced (DCE) imaging in patients with head and neck squamous cell carcinoma (HNSCC). Overall, 28 patients with primary HNSCC of different localizations were involved. 18F-FDG-PET/CT and DCE MR imaging were performed for all patients. Histogram analysis parameters of DCE MRI were calculated. Spearman's correlation coefficient was used to analyze the associations between investigated parameters. In the overall cohort, SUVmax correlated with Kep P10 (ρ=0.43, p=0.027), Kep P25 (0.40, p=0.035), and had a tendency to correlate with median Kep (ρ=0.33, p=0.098). TLG tended to correlate with Kep P25 (0.33, p=0.09) and P10 Ktrans (ρ=0.35, p=0.07). In G1/2 tumors, SUVmax correlated with Kep P10 (ρ=0.645, p=0.032), and tended to correlate with Ktrans mean (ρ=0.54, p=0.089), Ktrans min (ρ=0.58, p=0.06), Ktrans P10 (ρ=0.56, p=0.07), Ktrans P25 (ρ=0.59, p=0.056), and Ktrans median (ρ=0.054, p=0.089), as well with Kep min (ρ=0.56, p=0.07). SUVmean tended to correlate with Kep kurtosis (ρ=0.56, p=0.07). In G3 tumors, no tendencies or statistically significant correlations between the PET and DCE MRI parameters were identified. Tumor metabolism and perfusion show complex associations in HNSCC. These associations depend on tumor grading.

Tau-PET imaging with [18F]AV-1451 in primary progressive apraxia of speech

Apraxia of speech is a motor speech disorder characterized by combinations of slow speaking rate, abnormal prosody, distorted sound substitutions, and trial-and-error articulatory movements. Apraxia of speech is due to abnormal planning and/or programming of speech production. It is referred to as primary progressive apraxia of speech (PPAOS) when it is the only symptom of a neurodegenerative condition. Past reports suggest an association of PPAOS with primary 4-repeat (4R) tau (e.g., progressive supranuclear palsy, corticobasal degeneration), rather than amyloid, pathology. The goal of the current study was to investigate the distribution of tau tracer uptake using [18F]AV-1451 positron emission tomography (PET) imaging in patients with PPAOS. Fourteen PPAOS patients underwent [18F]AV-1451 PET (tau-PET) imaging, [C11] Pittsburgh Compound B (PiB) PET and structural MRI and were matched 3:1 by age and sex to 42 cognitively normal controls. Tau-PET uptake was assessed at the region-of-interest (ROI) level and at the voxel-level. The PPAOS group (n = 14) showed increased tau-PET uptake in the precentral gyrus, supplementary motor area and Broca's area compared to controls. To examine whether tau deposition in Broca's area was related to the presence of aphasia, we examined a subgroup of the PPAOS patients who had predominant apraxia of speech, with concomitant aphasia (PPAOSa; n = 7). The PPAOSa patients showed tau-PET uptake in the same regions as the whole group. However, the remaining seven patients who did not have aphasia showed uptake only in superior premotor and precentral cortices, with no uptake observed in Broca's area. This cross-sectional study demonstrates that elevated tau tracer uptake is observed using [18F]AV-1451 in PPAOS. Further, it appears that [18F]AV-1451 is sensitive to the regional distribution of tau deposition in different stages of PPAOS, given the relationship between tau signal in Broca's area and the presence of aphasia.

Updates on the role of imaging in the assessment of crohn's disease

As initial studies reported that magnetic resonance imaging (MRI) was useful for the evaluation of the small intestine, this modality has become increasingly important in the diagnosis, assessment and exclusion of small bowel disease. The use of MRI for the assessment of inflammatory bowel disease is increasing, at the expense of the current primary imaging modality and computed tomography (CT) enterography. MRI has many advantages over CT, including a lack of radiation exposure, lower prevalence of adverse events, availability of dynamic information, higher resolution and better soft-tissue contrast. New MRI techniques, including diffusion-weighted imaging, spectroscopy, motility study, positron-emission tomography-MRI and molecular imaging, are currently under investigation to improve the diagnosis, follow-up and management of the disease.

Flortaucipir tau PET imaging in semantic variant primary progressive aphasia

ObjectiveThe semantic variant of primary progressive aphasia (svPPA) is typically associated with frontotemporal lobar degeneration (FTLD) with longTAR DNA-binding protein (TDP)-43-positive neuropil threads and dystrophic neurites (type C), and is...

Effect of Citalopram on Emotion Processing in Humans: A Combined 5-HT1A [11C]CUMI-101 PET and Functional MRI Study

A subset of patients started on a selective serotonin reuptake inhibitor (SSRI) initially experience increased anxiety, which can lead to early discontinuation before therapeutic effects are manifest. The neural basis of this early SSRI effect is not known. Presynaptic dorsal raphe neuron (DRN) 5-HT1A receptors are known to have a critical role in affect processing. Thus we investigated the effect of acute citalopram on emotional processing and the relationship between DRN 5-HT1A receptor availability and amygdala reactivity. Thirteen (mean age 48±9 years) healthy male subjects received either a saline or citalopram infusion intravenously (10 mg over 30 min) on separate occasions in a single-blind, random order, crossover design. On each occasion, participants underwent a block design face-emotion processing task during fMRI known to activate the amygdala. Ten subjects also completed a positron emission tomography (PET) scan to quantify DRN 5-HT1A availability using [11C]CUMI-101. Citalopram infusion when compared with saline resulted in a significantly increased bilateral amygdala responses to fearful vs neutral faces (left p=0.025; right p=0.038 FWE-corrected). DRN [11C]CUMI-101 availability significantly positively correlated with the effect of citalopram on the left amygdala response to fearful faces (Z=2.51, p=0.027) and right amygdala response to happy faces (Z=2.33, p=0.032). Our findings indicate that the initial effect of SSRI treatment is to alter processing of aversive stimuli and that this is linked to DRN 5-HT1A receptors in line with evidence that 5-HT1A receptors have a role in mediating emotional processing.

Brain PET and functional MRI: why simultaneously using hybrid PET/MR systems?

In the last 20 years growing attention has been devoted to multimodal imaging. The recent literature is rich of clinical and research studies that have been performed using different imaging modalities on both separate and integrated positron emission tomography (PET) and magnetic resonance (MR) scanners. However, today, hybrid PET/MR systems measure signals related to brain structure, metabolism, neurochemistry, perfusion, and neuronal activity simultaneously, i.e. in the same physiological conditions. A frequently raised question at meeting and symposia is: "Do we really need a hybrid PET/MR system? Are there any advantages over acquiring sequential and separate PET and MR scans?" The present paper is an attempt to answer these questions specifically in relation to PET combined with functional magnetic resonance imaging (fMRI) and arterial spin labeling. We searched (last update: June 2017) the databases PubMed, PMC, Google Scholar and Medline. We also included additional studies if they were cited in the selected articles. No language restriction was applied to the search, but the reviewed articles were all in English. Among all the retrieved articles, we selected only those performed using a hybrid PET/MR system. We found a total of 17 papers that were selected and discussed in three main groups according to the main radiopharmaceutical used: 18F-fluorodeoxyglucose (18F-FDG) (N.=8), 15O-water (15O-H2O) (N.=3) and neuroreceptors (N.=6). Concerning studies using 18F-FDG, simultaneous PET/fMRI revealed that global aspects of functional organization (e.g. graph properties of functional connections) are partially associated with energy consumption. There are remarkable spatial and functional similarities across modalities, but also discrepant findings. More work is needed on this point. There are only a handful of papers comparing blood flow measurements with PET 15O-H2O and MR arterial spin label (ASL) measures, and they show significant regional CBF differences between these two modalities. However, at least in one study the correlation at the level of gray, white matter, and whole brain is rather good (r=0.94, 0.8, 0.81 respectively). Finally, receptor studies show that simultaneous PET/fMRI could be a useful tool to characterize functional connectivity along with dynamic neuroreceptor adaptation in several physiological (e.g. working memory) or pathological (e.g. pain) conditions, with or without drug administrations. The simultaneous acquisition of PET (using a number of radiotracers) and functional MRI (using a number of sequences) offers exciting opportunities that we are just beginning to explore. The results thus far are promising in the evaluation of cerebral metabolism/flow, neuroreceptor adaptation, and network's energetic demand.

Imaging increased glutamate in children with Sturge–Weber syndrome: Association with epilepsy severity

BackgroundSturge–Weber syndrome (SWS) is strongly associated with epilepsy. Brain tissue studies have suggested that epileptic activity in SWS is driven by glutamatergic synaptic activity. Here, we used proton magnetic resonance spectroscopic imaging (MRSI) to test if glutamate (GLU) concentrations are increased in the affected hemisphere and if such increases are associated with severity of epilepsy in children with SWS. We also studied the metabolic correlates of MRSI abnormalities, using glucose positron emission tomography (PET) imaging. Methods3T MRI and glucose PET were performed in 10 children (age: 7–78 months) with unilateral SWS and a history of epilepsy. MRSI data were acquired from the affected (ipsilateral) and non-affected (contralateral) hemispheres. GLU, N-acetyl-aspartate (NAA) and creatine (Cr) were quantified in multiple voxels; GLU/Cr and NAA/Cr ratios were calculated and compared to seizure frequency as well as glucose PET findings. ResultsThe highest GLU/Cr ratios were found in the affected hemisphere in all children except one with severe atrophy. The maximum ipsilateral/contralateral GLU/Cr ratios ranged between 1.0 and 2.5 (mean: 1.6). Mean ipsilateral/contralateral GLU/Cr ratios were highest in the youngest children and showed a strong positive correlation with clinical seizure frequency scores assessed at the time of the scan (r=0.88, p=0.001) and also at follow-up (up to 1 year, r=0.80, p=0.009). GLU increases in the affected hemisphere coincided with areas showing current or previous increases of glucose metabolism on PET in 5 children. NAA/Cr ratios showed no association with clinical seizure frequency. ConclusionsIncreased glutamate concentrations in the affected hemisphere, measured by MRSI, are common in young children with unilateral SWS and are associated with frequent seizures. The findings lend support to the role of excess glutamate in SWS-associated epilepsy.

Quantitative agreement between [(15)O]H2O PET and model free QUASAR MRI-derived cerebral blood flow and arterial blood volume.

The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [(15)O]H2O positron emission tomography (PET) and model-free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r(2): 0.28-0.60, P < 0.05), although QUASAR significantly underestimated CBF by 30% (P < 0.001). CBVA was moderately correlated (r(2): 0.28-0.43, P < 0.05), with QUASAR yielding values that were only 27% of the [(15)O]H2O-derived values (P < 0.001). Group-wise voxel statistics identified minor areas with significant contrast differences between [(15)O]H2O PET and QUASAR MRI, indicating similar qualitative CBVA and CBF information by both modalities. In conclusion, the results of this study demonstrate that QUASAR MRI and [(15)O]H2O PET provide similar CBF and CBVA information, but with systematic quantitative discrepancies.