Impact of cannabidiol on brain glucose metabolism of C57Bl/6 male mice previously exposed to cocaine.

Despite evidence of the beneficial effects of cannabidiol (CBD) in animal models of cocaine use disorder (CUD), CBD neuronal mechanisms remain poorly understood. This study investigated the effects of CBD treatment on brain glucose metabolism, in a CUD animal model, using [18F]FDG positron emission tomography (PET). Male C57Bl/6 mice were injected with cocaine (20 mg/kg, i.p.) every other day for 9 days, followed by 8 days of CBD administration (30 mg/kg, i.p.). After 48 h, animals were challenged with cocaine. Control animals received saline/vehicle. [18F]FDG PET was performed at four time points: baseline, last day of sensitization, last day of withdrawal/CBD treatment, and challenge. Subsequently, the animals were euthanized and immunohistochemistry was performed on the hippocampus and amygdala to assess the CB1 receptors, neuronal nuclear protein, microglia (Iba1), and astrocytes (GFAP). Results showed that cocaine administration increased [18F]FDG uptake following sensitization. CBD treatment also increased [18F]FDG uptake in both saline and cocaine groups. However, animals that were sensitized and challenged with cocaine, and those receiving only an acute cocaine injection during the challenge phase, did not exhibit increased [18F]FDG uptake when treated with CBD. Furthermore, CBD induced modifications in the integrated density of NeuN, Iba, GFAP, and CB1R in the hippocampus and amygdala. This is the first study addressing the impact of CBD on brain glucose metabolism in a preclinical model of CUD using PET. Our findings suggest that CBD disrupts cocaine-induced changes in brain energy consumption and activity, which might be correlated with alterations in neuronal and glial function.

Impact of baseline and interim quantitative PET parameters on outcomes of classical Hodgkin Lymphoma.

Currently, analysis of interim PET (iPET) according to the Deauville score (DS) is the most important predictive factor in Hodgkin lymphoma (HL); however, there is room for improvement in its prognostic power. This study aimed to evaluate the prognostic value of quantitative PET analysis (maximum standard uptake value [SUVmax], total metabolic tumor volume [TMTV] and total lesion glicolysis [TLG]) at baseline (PET0) and iPET in a retrospective cohort of newly diagnosed classical HL. For positive iPET (+ iPET), the reduction of quantitative parameters in relation to PET0 (ΔSUVmax, ΔTMTV and ΔTLG) was calculated. Between 2011 and 2017, 234 patients treated with ABVD were analyzed. Median age was 30 years-old, 59% had advanced stage disease, 57% a bulky mass and 25% a + iPET (DS 4-5). At baseline, high TLG was associated with an increased cumulative incidence of failure (CIF) (p = 0.032) while neither SUVmax, TMTV or TLG were associated with overall survival (OS) or progression-free survival (PFS). In multivariate analysis, only iPET was associated with CIF (p < 0.001). Among ΔSUVmax, ΔTMTV and ΔTLG, only a ΔSUVmax ≥ 68.8 was significant for PFS (HR: 0.31, CI95%: 0.11-0.86, p = 0.024). A subset of patients with improved PFS amongst + iPET was identified by the quantitative (ΔSUVmax ≥ 68.8%) analysis. In this real-world Brazilian cohort, with prevalent high-risk patients, quantitative analysis of PET0 did not demonstrate to be prognostic, while a dynamic approach incorporating the ΔSUVmax to + iPET succeeded in refining a subset with better prognosis. These findings warrant validation in larger series and indicate that not all patients with + iPET might need treatment intensification.

Segmental cardiac strain assessment by two-dimensional speckle-tracking echocardiography in surviving MIS-c patients: Correlations with myocardial flow reserve (MFR) by 13 N-ammonia PET-CT.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-c) is associated with severe cardiovascular impairment and eventually death. Pathophysiological mechanisms involved in myocardial injury were scarcely investigated, and cardiovascular outcomes are uncertain. Autopsy studies suggested that microvascular dysfunction may be relevant to LV impairment. OBJECTIVE: We aimed to evaluate segmental LV longitudinal strain by 2DST echocardiography and myocardial flow reserve (MFR) by 13 N-ammonia PET-CT, in six surviving MIS-c patients. METHODS: Each patient generated 34 LV segments for combined 2DST and MRF analysis. MFR was considered abnormal when <2, borderline when between 2 and 2.5 and normal when >2.5. RESULTS: From July 2020 to February 2021, six patients were admitted with MIS-c: three males, aged 9.3 (6.6-15.7) years. Time from admission to the follow-up visit was 6.05 (2-10.3) months. Although all patients were asymptomatic and LV EF was ≥55%, 43/102 (42.1%) LV segments showed MFR <2.5. There was a modest positive correlation between segmental peak systolic longitudinal strain and MFR: r = .36, p = .03 for basal segments; r = .41, p = .022 for mid segments; r = .42, p = .021 for apical segments. Median peak systolic longitudinal strain was different among MRF categories: 18% (12%-24%) for abnormal, 18.5% (11%-35%) for borderline, and 21% (12%-32%) for normal MFR (p = .006). CONCLUSION: We provided preliminary evidence that surviving MIS-c patients may present subclinical impairment of myocardial microcirculation. Segmental cardiac strain assessment 2DST seems useful for MIS-c cardiovascular follow-up, given its good correlation with 13 N-ammonia PET-CT derived MFR.

[18 F]FDG brain uptake of C57Bl/6 male mice is affected by locomotor activity after cocaine use: A small animal positron emission tomography study.

We verified if cocaine-induced peripheral activation might disrupt [18 F]FDG brain uptake after a cocaine challenge and suggested an optimal protocol to measure cocaine-induced brain metabolic alterations in mice. C57Bl/6 male mice were injected with [18 F]FDG and randomly separated into three groups. Groups 1 and 2 were kept conscious after [18 F]FDG administration and after 5 min received saline or cocaine (20 mg/kg). The animals in group 1 (n = 5) were then evaluated in the open field for 30 min and those from group 2 (n = 6) were kept alone in a home cage for the same period. Forty-five minutes after [18 F]FDG administration, images were acquired for 30 min. Group 3 (n = 6) was kept anesthetized and image acquisition started immediately after tracer injection, for 75 min. Saline (Day 1) or cocaine (Day 2) was injected 5 min after starting acquisition. Another set of animals (n = 5) were treated with cocaine every other day for 10 days or saline (n = 6) and were scanned with the dynamic protocol to verify its efficacy. [18 F]FDG uptake increased after cocaine administration when compared to baseline only in animals kept under anesthesia. No brain effect of cocaine was observed in animals submitted to the open field or kept in the home cage. The use of anesthesia is essential to visualize cocaine-induced changes in brain metabolism by [18 F]FDG PET, providing an interesting preclinical approach to investigate naïve subjects and enabling a bidirectional translational science approach for better understanding of cocaine use disorder.

Is positron emission tomography/magnetic resonance imaging a reliable tool for detecting vascular activity in treated childhood-onset Takayasu's arteritis? A multicentre study.

OBJECTIVES: Toassess whether 18F-fluordeoxiglucose (18F-FDG) PET/MRI) with angiographic sequences can contribute to detecting vessel wall inflammation in patients with childhood-onset Takayasu's arteritis (c-TA) under immunosuppressive therapy. METHODS: A three-centre cross-sectional study was conducted. 18F-FDG PET/MRI scans were performed in c-TA patients and in oncologic patients, who served as the control group. Clinical and laboratory characteristics were also analysed. RESULTS: Seventeen c-TA patients (65% females) between the ages of 6 and 21 years with a mean disease duration of 9.4 years were recruited. Only one patient presented clinical disease activity and six (35.6%) had increased ESR and/or CRP levels. The most frequent magnetic resonance angiography (MRA) findings were stenosis and thickening, observed in 82.4 and 70.6% of c-TA patients, respectively. 18F-FDG PET revealed 18F-FDG uptake greater than the liver in at least one arterial segment in 15 (88.2%) patients in a qualitative analysis and a median maximum standardized uptake value (SUVmax) of 3.22 (interquartile range 2.76-3.69) in a semi-quantitative analysis. c-TA patients presented significantly higher SUVmax values than oncologic patients (P < 0.001). A positive correlation between SUVmax and CRP levels (ρ = 0.528, P = 0.029) was seen. CONCLUSION: A state-of-the-art imaging modality was used in c-TA patients and revealed a strong arterial FDG uptake even in patients in apparent remission. We suppose that this finding may represent silent activity in the vessel wall; however, we cannot exclude the possibility of arterial remodelling. Importantly, a negative imaging scan may help in immunosuppression withdrawal in daily clinical practice.

Innate immune cells and myelin profile in multiple sclerosis: a multi-tracer PET/MR study.

PURPOSE: Neuropathological studies have demonstrated distinct profiles of microglia activation and myelin injury among different multiple sclerosis (MS) phenotypes and disability stages. PET imaging using specific tracers may uncover the in vivo molecular pathology and broaden the understanding of the disease heterogeneity. METHODS: We used the 18-kDa translocator protein (TSPO) tracer (R)-[11C]PK11195 and [11C]PIB PET images acquired in a hybrid PET/MR 3 T system to characterize, respectively, the profile of innate immune cells and myelin content in 47 patients with MS compared to 18 healthy controls (HC). For the volume of interest (VOI)-based analysis of the dynamic data, (R)-[11C]PK11195 distribution volume (VT) was determined for each subject using a metabolite-corrected arterial plasma input function while [11C]PIB distribution volume ratio (DVR) was estimated using a reference region extracted by a supervised clustering algorithm. A voxel-based analysis was also performed using Statistical Parametric Mapping. Functional disability was evaluated by the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Symbol Digit Modality Test (SDMT). RESULTS: In the VOI-based analysis, [11C]PIB DVR differed between patients and HC in the corpus callosum (P = 0.019) while no differences in (R)-[11C]PK11195 VT were observed in patients relative to HC. Furthermore, no correlations or associations were observed between both tracers within the VOI analyzed. In the voxel-based analysis, high (R)-[11C]PK11195 uptake was observed diffusively in the white matter (WM) when comparing the progressive phenotype and HC, and lower [11C]PIB uptake was observed in certain WM regions when comparing the relapsing-remitting phenotype and HC. None of the tracers were able to differentiate phenotypes at voxel or VOI level in our cohort. Linear regression models adjusted for age, sex, and phenotype demonstrated that higher EDSS was associated with an increased (R)-[11C]PK11195 VT and lower [11C]PIB DVR in corpus callosum (P = 0.001; P = 0.023), caudate (P = 0.015; P = 0.008), and total T2 lesion (P = 0.007; P = 0.012), while better cognitive scores in SDMT were associated with higher [11C]PIB DVR in the corpus callosum (P = 0.001), and lower (R)-[11C]PK11195 VT (P = 0.013). CONCLUSIONS: Widespread innate immune cells profile and marked loss of myelin in T2 lesions and regions close to the ventricles may occur independently and are associated with disability, in both WM and GM structures.

Cannabidiol Treatment Improves Glucose Metabolism and Memory in Streptozotocin-Induced Alzheimer's Disease Rat Model: A Proof-of-Concept Study.

An early and persistent sign of Alzheimer's disease (AD) is glucose hypometabolism, which can be evaluated by positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose ([18F]FDG). Cannabidiol has demonstrated neuroprotective and anti-inflammatory properties but has not been evaluated by PET imaging in an AD model. Intracerebroventricular (icv) injection of streptozotocin (STZ) is a validated model for hypometabolism observed in AD. This proof-of-concept study evaluated the effect of cannabidiol treatment in the brain glucose metabolism of an icv-STZ AD model by PET imaging. Wistar male rats received 3 mg/kg of STZ and [18F]FDG PET images were acquired before and 7 days after STZ injection. Animals were treated with intraperitoneal cannabidiol (20 mg/kg-STZ-cannabidiol) or saline (STZ-saline) for one week. Novel object recognition was performed to evaluate short-term and long-term memory. [18F]FDG uptake in the whole brain was significantly lower in the STZ-saline group. Voxel-based analysis revealed a hypometabolism cluster close to the lateral ventricle, which was smaller in STZ-cannabidiol animals. The brain regions with more evident hypometabolism were the striatum, motor cortex, hippocampus, and thalamus, which was not observed in STZ-cannabidiol animals. In addition, STZ-cannabidiol animals revealed no changes in memory index. Thus, this study suggests that cannabidiol could be an early treatment for the neurodegenerative process observed in AD.

Hippocampal subregional volume changes in elders classified using positron emission tomography-based Alzheimer's biomarkers of ß-amyloid deposition and neurodegeneration.

Changes in hippocampal subfield volumes (HSV) along the Alzheimer's disease (AD) continuum have been scarcely investigated to date in elderly subjects classified based on the presence of ß-amyloid aggregation and signs of neurodegeneration. We classified patients (either sex) with mild dementia compatible with AD (n = 35) or amnestic mild cognitive impairment (n = 39), and cognitively unimpaired subjects (either sex; n = 26) using [11 C]PIB-PET to assess ß-amyloid aggregation (A+) and [18 F]FDG-PET to account for neurodegeneration ((N)+). Magnetic resonance imaging-based automated methods were used for HSV and white matter hyperintensity (WMH) measurements. Significant HSV reductions were found in A+(N)+ subjects in the presubiculum/subiculum complex and molecular layer, related to worse memory performance. In both the A+(N)+ and A+(N)- categories, subicular volumes were inversely correlated with the degree of Aß deposition. The A-(N)+ subgroup showed reduced HSV relative to the A-(N)- subgroup also in the subiculum/presubiculum. Combining all (N)- subjects, HSV were lower in subjects presenting significant cognitive decline irrespective of A+/A- classification (controlling for WMH load); these between-group differences were detected again in the presubiculum, but also involved the CA4 and granular layer. These findings demonstrate that differential HSV reductions are detectable both in (N)+ and (N)- categories along the AD continuum, and are directly related to the severity of cognitive deficits. HSV reductions are larger both in A+(N)+ and A+(N)- subjects in direct proportion to the degree of Aß deposition. The meaningful HSV reductions detected in the A-(N)+ subgroup highlights the strength of biomarker-based classifications outside of the classical AD continuum.

Diagnostic accuracy of FDG-PET/MRI versus pelvic MRI and thoracic and abdominal CT for detecting synchronous distant metastases in rectal cancer patients.

PURPOSE: We compared the diagnostic accuracy of detecting distant metastases for baseline rectal cancer staging between PET/MRI and conventional staging (CS). MATERIALS AND METHODS: This prospective study from November 2016 to April 2018 included 101 rectal adenocarcinoma patients for primary staging. These patients underwent whole-body PET/MRI in addition to CS (pelvic MRI and thoracic and abdominal contrast-enhanced CT). Different readers analyzed CS and PET/MRI findings for primary tumor, nodal, and metastatic staging. The presence, number, and location of metastases were recorded according to the organ involved (non-regional lymph nodes (LNs), liver, lungs, or others). Lesions were defined as positive, negative, or indeterminate. The number of lesions per organ was limited to 10. The McNemar test was used to compare the accuracies. RESULTS: PET/MRI exhibited a higher accuracy in detecting metastatic disease than CS in all patients (88.4% vs. 82.6%, p = 0.003) and in patients with extramural vascular invasion (EMVI) (88.9% vs. 85.5%, p = 0.013). The detection rate of PET/MRI was superior to that of CS for all lesions [84.1% vs. 68.9%, p = 0.001], as well as those in the liver (89.2% vs. 84.2%), non-regional LNs (90.0% vs. 36.7%), and lungs (76.4% vs. 66.9%). PET/MRI correctly classified 19/33 (57.5%) patients with indeterminate lesions on CS. CONCLUSION: PET/MRI yields higher accuracy than CS for detecting distant synchronous metastases in the baseline staging of patients with rectal cancer and EMVI. PET/MRI exhibited a higher detection rate than CS for identifying non-regional LNs, hepatic lesions, and pulmonary lesions as well as correctly classifying patients with indeterminate lesions. TRIAL REGISTRATION: NCT02537340.

FDG-PET Patterns Predict Amyloid Deposition and Clinical Profile in Corticobasal Syndrome.

BACKGROUND: Corticobasal syndrome (CBS) is an atypical parkinsonian syndrome related to multiple underlying pathologies. OBJECTIVE: To investigate if individual brain [18 F]fluorodeoxyglucose-positron emission tomography (FDG-PET) patterns could distinguish CBS due to Alzheimer's disease (AD) from other pathologies based on [11 C]Pittsburgh Compound-B (PIB)-PET. METHODS: Forty-five patients with probable CBS were prospectively evaluated regarding cognitive and movement disorders profile. They underwent FDG-PET and were distributed into groups: likely related to AD (CBS FDG-AD) or likely non-AD (CBS FDG-nonAD) pathology. Thirty patients underwent PIB-PET on a hybrid PET-magnetic resonance imaging equipment to assess their amyloid status. FDG and PIB-PET images were classified individually based on visual and semi-quantitative analysis, blinded to each other. Quantitative group analyses were also performed. RESULTS: CBS FDG-AD group demonstrated worse cognitive performances, mostly concerning attention, memory, visuospatial domains, and displayed more myoclonus and hallucinations. The non-AD metabolic group presented more often limb dystonia, ocular motor dysfunction, motor perseveration, and dysarthria. All patients classified as CBS FDG-AD tested positive at PIB-PET compared to 3 of 20 in the non-AD group. The individual FDG-PET classification demonstrated 76.92% of sensitivity, 100% of specificity and positive predictive value and 88.5% of balanced accuracy to detect positive PIB-PET scans. Individuals with positive and negative PIB-PET showed hypometabolism in posterior temporoparietal areas and in thalamus and brainstem, respectively, mainly contralateral to most affected side, disclosing possible metabolic signatures of CBS variants. CONCLUSION: FDG-PET was useful to predict AD and non-AD CBS variants depicting their specific degeneration patterns, different clinical features, and brain amyloid deposition. © 2020 International Parkinson and Movement Disorder Society.

PET/MRI Characterization of Mucinous Versus Nonmucinous Components of Rectal Adenocarcinoma: A Comparison of Tumor Metabolism and Cellularity.

OBJECTIVE. The purpose of this study was to evaluate whether FDG PET/MRI can be used to differentiate the mucinous from the nonmucinous components of primary rectal tumors and to compare the glycolytic metabolism on PET with tumor cellularity on DWI in both components. SUBJECTS AND METHODS. Ninety-nine patients who underwent FDG PET/MRI for staging of primary rectal cancer were included in this prospective analysis. MRI depicted the mucin component through the tumor volume. Separate volumes of interest were drawn on both mucinous and nonmucinous components and propagated to PET and apparent diffusion coefficient (ADC) mapping. Maximum and mean standardized uptake values (SUVmax, SUVmean) and maximum, mean, and minimum ADC values (ADCmax, ADCmean, ADCmin) were recorded and compared between areas with mucinous and nonmucinous components. Whole-body PET/MRI was also used to evaluate for the presence of distant metastases. Nonparametric testing was used to compare the two groups of patients: those with tumors with a mucinous component and those with tumors without a mucinous component. Logistic regression analysis was performed to calculate the association risk between mucinous component and metastatic disease. RESULTS. Seventeen patients (17.2%) had a mucinous component within the tumor on T2-weighted MRI. Most of these patients had advanced disease, the mucinous component tumors being in significantly higher T categories than the tumors without a mucinous component (88.2% vs 61.0%; p = 0.032). SUVmax (7.4 vs 16.7; p = 0.002) and SUVmean (5.4 vs 13.4; p = 0.001) were significantly lower in tumors with a mucinous component than in those without a mucinous component. Tumor ADC measurements were not different between tumors with and those without a mucinous component (ADCmean, 1.4 vs 1.6; p = 0.361). There was no association between presence of a mucinous component within the primary rectal tumor and presence of synchronous metastases (odds ratio, 1.1 [0.4-3.0]; p = 0.904). Moreover, the occurrence of metastases in patients with mucinous component tumors (7/17 [41.2%]) was not different from that in patients with tumors without a mucinous component (28/82 [34.1%]) (p = 0.887). CONCLUSION. PET/MRI can be used to differentiate the mucinous and nonmucinous components within primary rectal adenocarcinoma on the basis of metabolic status. The FDG uptake is significantly lower in the mucinous component, but tumor cellularity based on MRI and DWI findings is not. Despite being associated with a higher T category in the sample of patients in this study, the presence of a mucinous component seems not to be associated with increased risk of synchronous metastases.

Reassessing Patterns of Response to Immunotherapy with PET: From Morphology to Metabolism.

Cancer demands precise evaluation and accurate and timely assessment of response to treatment. Imaging must be performed early during therapy to allow adjustments to the course of treatment. For decades, cross-sectional imaging provided these answers, showing responses to the treatment through changes in tumor size. However, with the emergence of immune checkpoint inhibitors, complex immune response patterns were revealed that have quickly highlighted the limitations of this approach. Patterns of response beyond tumor size have been recognized and include cystic degeneration, necrosis, hemorrhage, and cavitation. Furthermore, new unique patterns of response have surfaced, like pseudoprogression and hyperprogression, while other patterns were shown to be deceptive, such as unconfirmed progressive disease. This evolution led to new therapeutic evaluation criteria adapted specifically for immunotherapy. Moreover, inflammatory adverse effects of the immune checkpoint blockade were identified, many of which were life threatening and requiring prompt intervention. Given complex concepts like tumor microenvironment and novel therapeutic modalities in the era of personalized medicine, increasingly sophisticated imaging techniques are required to address the intricate patterns of behavior of different neoplasms. Fluorine 18-fluorodeoxyglucose PET/CT has rapidly emerged as one such technique that spans both molecular biology and immunology. This imaging technique is potentially capable of identifying and tracking prognostic biomarkers owing to its combined use of anatomic and metabolic imaging, which enables it to characterize biologic processes in vivo. This tailored approach may provide whole-body quantification of the metabolic burden of disease, providing enhanced prediction of treatment response and improved detection of adverse events. ©RSNA, 2020.

Deficits in short-term memory binding are detectable in individuals with brain amyloid deposition in the absence of overt neurodegeneration in the Alzheimer's disease continuum.

The short-term memory binding (STMB) test involves the ability to hold in memory the integration between surface features, such as shapes and colours. The STMB test has been used to detect Alzheimer's disease (AD) at different stages, from preclinical to dementia, showing promising results. The objective of the present study was to verify whether the STMB test could differentiate patients with distinct biomarker profiles in the AD continuum. The sample comprised 18 cognitively unimpaired (CU) participants, 30 mild cognitive impairment (MCI) and 23 AD patients. All participants underwent positron emission tomography (PET) with Pittsburgh compound-B labelled with carbon-11 ([11C]PIB) assessing amyloid beta (Aß) aggregation (A) and 18fluorine-fluorodeoxyglucose ([18F]FDG)-PET assessing neurodegeneration (N) (A-N- [n = 35]); A+N- [n = 11]; A+ N+ [n = 19]). Participants who were negative and positive for amyloid deposition were compared in the absence (A-N- vs. A+N-) of neurodegeneration. When compared with the RAVLT and SKT memory tests, the STMB was the only cognitive task that differentiated these groups, predicting the group outcome in logistic regression analyses. The STMB test showed to be sensitive to the signs of AD pathology and may represent a cognitive marker within the AD continuum.

The Role of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis of Left-sided Endocarditis: Native vs Prosthetic Valves Endocarditis.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) has emerged as a useful diagnostic tool for suspected infective endocarditis (IE) in patients with prosthetic valves or implantable devices. However, there is limited evidence regarding use of 18F-FDG-PET/CT for the diagnosis of native valve endocarditis (NVE). METHODS: Between 2014 and 2017, 303 episodes of left-sided suspected IE (188 prosthetic valves/ascending aortic prosthesis and 115 native valves) were studied. 18F-FDG-PET/CT accuracy was determined in the subgroups of patients with NVE and prosthetic valve endocarditis (PVE)/ascending aortic prosthesis infection (AAPI). Associations between inflammatory infiltrate patterns and 18F-FDG-PET/CT uptake were investigated in an exploratory ad hoc histological analysis. RESULTS: Among 188 patients with PVE/AAPI, the sensitivity, specificity, and positive and negative predictive values of 18F-FDG-PET/CT focal uptake were 93%, 90%, 89%, and 94%, respectively, while among 115 patients with NVE, the corresponding values were 22%, 100%, 100%, and 66%. The inclusion of abnormal 18F-FDG cardiac uptake as a major criterion at admission enabled a recategorization of 76% (47/62) of PVE/AAPI cases initially classified as "possible" to "definite" IE. In the histopathological analysis, a predominance of polymorphonuclear cell inflammatory infiltrate and a reduced extent of fibrosis were observed in the PVE group only. CONCLUSIONS: Use of 18F-FDG-PET/CT at the initial presentation of patients with suspected PVE increases the diagnostic capability of the modified Duke criteria. In patients who present with suspected NVE, the use of 18F-FDG-PET/CT is less accurate and could only be considered a complementary diagnostic tool for a specific population of patients with NVE.

Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters.

PURPOSE: [18F]FDG-PET and [11C]PIB-PET are validated as neurodegeneration and amyloid biomarkers of Alzheimer's disease (AD). We used a PET staging system based on the 2018 NIA-AA research framework to compare the proportion of amyloid positivity (A+) and hypometabolism ((N)+) in cases of mild probable AD, amnestic mild cognitive impairment (aMCI), and healthy controls, incorporating an additional classification of abnormal [18F]FDG-PET patterns and investigating the co-occurrence of such with A+, exploring [18F]FDG-PET to generate hypotheses in cases presenting with clinical-biomarker "mismatches." METHODS: Elderly individuals (N = 108) clinically classified as controls (N = 27), aMCI (N = 43) or mild probable AD (N = 38) were included. Authors assessed their A(N) profiles and classified [18F]FDG-PET neurodegenerative patterns as typical or non-typical of AD, performing re-assessments of images whenever clinical classification was in disagreement with the PET staging (clinical-biomarker "mismatches"). We also investigated associations between "mismatches" and sociodemographic and educational characteristics. RESULTS: AD presented with higher rates of A+ and (N)+. There was also a higher proportion of A+ and (N)+ individuals in the aMCI group in comparison to controls, however without statistical significance regarding the A staging. There was a significant association between amyloid positivity and AD (N)+ hypometabolic patterns typical of AD. Non-AD (N)+ hypometabolism was seen in all A- (N)+ cases in the mild probable AD and control groups and [18F]FDG-PET patterns classified such individuals as "SNAP" and one as probable frontotemporal lobar degeneration. All A- (N)- cases in the probable AD group had less than 4 years of formal education and lower socioeconomic status (SES). CONCLUSION: The PET-based staging system unveiled significant A(N) differences between AD and the other groups, whereas aMCI and controls had different (N) staging, explaining the cognitive impairment in aMCI. [18F]FDG-PET could be used beyond simple (N) staging, since it provided alternative hypotheses to cases with clinical-biomarker "mismatches." An AD hypometabolic pattern correlated with amyloid positivity. Low education and SES were related to dementia in the absence of biomarker changes.

Correction to: Brain PET amyloid and neurodegeneration biomarkers in the context of the 2018 NIA-AA research framework: an individual approach exploring clinical-biomarker mismatches and sociodemographic parameters.

In the last paragraph of the subsession "Recruitment of the study population and clinical Evaluation" (Material and methods session).

Prostate-specific Membrane Antigen PET: Therapy Response Assessment in Metastatic Prostate Cancer.

Therapy response assessment is a critical step in cancer management, leading clinicians to optimize the use of therapeutic options during the course of the disease. Imaging is a pivotal biomarker for therapy response evaluation in oncology and has gained wider use through the development of reproducible data-based guidelines, of which the Response Evaluation Criteria in Solid Tumors is the most successful example. Disease-specific criteria have also been proposed, and the Prostate Cancer Working Group 3 criteria are the mainstay for prostate cancer (PC). However, conventional imaging evaluation in metastatic PC has several limitations, including (a) the inability to detect small-volume disease, (b) the high prevalence of bone (nonmeasurable) lesions at imaging, and (c) the established role of serum prostate-specific antigen (PSA) levels as the biomarker of choice for response assessment and disease progression. In addition, there are an increasing number of newer treatment options with various effects on imaging features. Prostate-specific membrane antigen (PSMA) PET has improved patient selection for newer treatments, such as metastasis-directed therapy (MDT) or radionuclide therapy. The role of PSMA PET in response assessment for many metastatic PC therapeutic options (MDT, androgen deprivation therapy, chemotherapy, radionuclide therapy, and immunotherapy) is an evolving issue, with emerging data showing good correlation with PSA levels and clinical outcome. However, there are specific implications of each therapy (especially androgen deprivation therapy and immunotherapy) on PSMA expression by PC cells, leading to potential pitfalls and inaccuracies that must be known by radiologists. Despite some limitations, PSMA PET is addressing gaps left by conventional imaging methods (eg, CT and bone scanning) and nonimaging biomarkers (PSA levels) in metastatic PC therapy response assessment, a role that can be improved with advances like refinement of interpretation criteria and whole-body tumor burden quantification.© RSNA, 2020See discussion on this article by Barwick and Castellucci.

Theranostics in Nuclear Medicine: Emerging and Re-emerging Integrated Imaging and Therapies in the Era of Precision Oncology.

Theranostics refers to the pairing of diagnostic biomarkers with therapeutic agents that share a specific target in diseased cells or tissues. Nuclear medicine, particularly with regard to applications in oncology, is currently one of the greatest components of the theranostic concept in clinical and research scenarios. Theranostics in nuclear medicine, or nuclear theranostics, refers to the use of radioactive compounds to image biologic phenomena by means of expression of specific disease targets such as cell surface receptors or membrane transporters, and then to use specifically designed agents to deliver ionizing radiation to the tissues that express these targets. The nuclear theranostic approach has sparked increasing interest and gained importance in parallel to the growth in molecular imaging and personalized medicine, helping to provide customized management for various diseases; improving patient selection, prediction of response and toxicity, and determination of prognosis; and avoiding futile and costly diagnostic examinations and treatment of many diseases. The authors provide an overview of theranostic approaches in nuclear medicine, starting with a review of the main concepts and unique features of nuclear theranostics and aided by a retrospective discussion of the progress of theranostic agents since early applications, with illustrative cases emphasizing the imaging features. Advanced concepts regarding the role of fluorine 18-fluorodeoxyglucose PET in theranostics, as well as developments in and future directions of theranostics, are discussed. ©RSNA, 2020 See discussion on this article by Greenspan and Jadvar.

Laser Ablation of Benign Thyroid Nodules: A Prospective Pilot Study With a Preliminary Analysis of the Employed Energy.

BACKGROUND AND OBJECTIVES: To assess the effectiveness of ultrasound (US)-guided laser ablation of benign thyroid nodules (TNs) under different amounts of applied energy. STUDY DESIGN/MATERIALS AND METHODS: Thirty-four euthyroid patients with 5-18 ml TNs were enrolled: 21 (laser ablation) and 13 (clinical follow up) patients with a mean age of 56.2 ± 12.0 and 54.7 ± 14.7 years, respectively. The laser ablation protocol used a 1.064 mm wavelength diode laser source; 3.5 W output power; 1,100-1,500 J and 5-8 min/illumination; and one or two fibers/session. Clinical, laboratory, and US data were obtained immediately before treatment and at 6 and 12 months follow-up and were analyzed by Student's t test and Fisher's exact test. Low- and high-energy subgroups were subsequently defined, and the receiver operating characteristic (ROC) curves were calculated. RESULTS: Laser ablation follow-up showed an overall nodule volume reduction of more than 50%; improvement of symptoms and cosmetic complaints (P = 0.001); and stable laboratory data compared with the baseline and control groups. Minor complications were 9.5% ( n = 2). One or two fibers/session resulted in a similar nodule volume reduction among 10-18 ml nodules. Analysis of the applied energy suggested a 398.8 J/ml inferior cutoff (ROC curve: 0.889 sensitivity; 0.545 specificity) for the high-energy subgroup ( n = 14, mean 599.9 ± 136.5 J/ml) to reduce the nodule volume over time (-55.1% vs. -58.4%, P = 0.55). The low-energy subgroup ( n = 7, mean 240.2 ± 74.6 J/ml) did not show a persistent volume reduction ( P < 0.05) from the 6- to 12-month follow-ups (-56.6% vs. -53.7%). CONCLUSIONS: Laser ablation of benign TNs achieved technique efficacy at 12 months posttreatment, with clinical improvement and few minor side effects. A single fiber in a single session with a high deployed energy (>398.8 J/ml) may be associated with improved results, a finding to be confirmed with a larger series. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Therapeutic Efficiency of Multiple Applications of Magnetic Hyperthermia Technique in Glioblastoma Using Aminosilane Coated Iron Oxide Nanoparticles: In Vitro and In Vivo Study.

Magnetic hyperthermia (MHT) has been shown as a promising alternative therapy for glioblastoma (GBM) treatment. This study consists of three parts: The first part evaluates the heating potential of aminosilane-coated superparamagnetic iron oxide nanoparticles (SPIONa). The second and third parts comprise the evaluation of MHT multiple applications in GBM model, either in vitro or in vivo. The obtained heating curves of SPIONa (100 nm, +20 mV) and their specific absorption rates (SAR) stablished the best therapeutic conditions for frequencies (309 kHz and 557 kHz) and magnetic field (300 Gauss), which were stablished based on three in vitro MHT application in C6 GBM cell line. The bioluminescence (BLI) signal decayed in all applications and parameters tested and 309 kHz with 300 Gauss have shown to provide the best therapeutic effect. These parameters were also established for three MHT applications in vivo, in which the decay of BLI signal correlates with reduced tumor and also with decreased tumor glucose uptake assessed by positron emission tomography (PET) images. The behavior assessment showed a slight improvement after each MHT therapy, but after three applications the motor function displayed a relevant and progressive improvement until the latest evaluation. Thus, MHT multiple applications allowed an almost total regression of the GBM tumor in vivo. However, futher evaluations after the therapy acute phase are necessary to follow the evolution or tumor total regression. BLI, positron emission tomography (PET), and spontaneous locomotion evaluation techniques were effective in longitudinally monitoring the therapeutic effects of the MHT technique.