Clinical and neuroimaging characterization of the first frontotemporal dementia family carrying the MAPT p.K298E mutation.

We present an in-depth clinical and neuroimaging analysis of a family carrying the MAPT K298E mutation associated with frontotemporal dementia (FTD). Initial identification of this mutation in a single clinical case led to a comprehensive investigation involving four affected siblings allowing to elucidate the mutation's phenotypic expression.A 60-year-old male presented with significant behavioral changes and progressed rapidly, exhibiting speech difficulties and cognitive decline. Neuroimaging via FDG-PET revealed asymmetrical frontotemporal hypometabolism. Three siblings subsequently showed varied but consistent clinical manifestations, including abnormal behavior, speech impairments, memory deficits, and motor symptoms correlating with asymmetric frontotemporal atrophy observed in MRI scans.Based on the genotype-phenotype correlation, we propose that the p.K298E mutation results in early-onset behavioral variant FTD, accompanied by a various constellation of speech and motor impairment.This detailed characterization expands the understanding of the p.K298E mutation's clinical and neuroimaging features, underlining its role in the pathogenesis of FTD. Further research is crucial to comprehensively delineate the clinical and epidemiological implications of the MAPT p.K298E mutation.

A ROI-based quantitative pipeline for 18F-FDG PET metabolism and pCASL perfusion joint analysis: Validation of the 18F-FDG PET line.

In Mild Cognitive Impairment (MCI), the study of brain metabolism, provided by 18F-FluoroDeoxyGlucose Positron Emission Tomography (18F-FDG PET) can be integrated with brain perfusion through pseudo-Continuous Arterial Spin Labeling Magnetic Resonance sequences (MR pCASL). Cortical hypometabolism identification generally relies on wide control group datasets; pCASL control groups are instead not publicly available yet, due to lack of standardization in the acquisition parameters. This study presents a quantitative pipeline to be applied to PET and pCASL data to coherently analyze metabolism and perfusion inside 16 matching cortical regions of interest (ROIs) derived from the AAL3 atlas. The PET line is tuned on 36 MCI patients and 107 healthy control subjects, to agree in identifying hypometabolic regions with clinical reference methods (visual analysis supported by a vendor tool and Statistical Parametric Mapping, SPM, with two parametrizations here identified as SPM-A and SPM-B). The analysis was conducted for each ROI separately. The proposed PET analysis pipeline obtained accuracy 78 % and Cohen's к 60 % vs visual analysis, accuracy 79 % and Cohen's к 58 % vs SPM-A, accuracy 77 % and Cohen's к 54 % vs SPM-B. Cohen's к resulted not significantly different from SPM-A and SPM-B Cohen's к when assuming visual analysis as reference method (p-value 0.61 and 0.31 respectively). Considering SPM-A as reference method, Cohen's к is not significantly different from SPM-B Cohen's к as well (p-value = 1.00). The complete PET-pCASL pipeline was then preliminarily applied on 5 MCI patients and metabolism-perfusion regional correlations were assessed. The proposed approach can be considered as a promising tool for PET-pCASL joint analyses in MCI, even in the absence of a pCASL control group, to perform metabolism-perfusion regional correlation studies, and to assess and compare perfusion in hypometabolic or normo-metabolic areas.

Left and right corticobasal syndrome: comparison of cognitive profiles between metabolic imaging - matched groups.

BACKGROUND: Corticobasal syndrome (CBS) is typically asymmetric. Case reports suggest that left-hemisphere CBS (lhCBS) is associated with major language impairment, and right-hemisphere CBS (rhCBS) is associated with major visuospatial deficits, but no group study has ever verified these observations. In our study, we enrolled 49 patients with CBS, classified them as lhCBS or rhCBS based on asymmetry of hypometabolism on brain FDG-PET and compared their cognitive and behavioural profiles. METHODS: We defined asymmetry of hypometabolism upon visual inspection of qualitative PET images and confirmed it through paired comparison of left- and right-hemisphere FDG uptake values. The two groups were also matched for severity of hypometabolism within the more affected and more preserved hemispheres, to unravel differences in the cognitive profiles ascribable specifically to each hemisphere's functional specializations. All patients were assessed for memory, language, executive and visuospatial deficits, apraxia, neglect, dyscalculia, agraphia and behavioural disturbances. RESULTS: LhCBS (n. 26) and rhCBS (n. 23) patients did not differ for demographics, disease duration and severity of global cognitive impairment. The two cognitive profiles were largely overlapping, with two exceptions: Digit span forward was poorer in lhCBS, and visual neglect was more frequent in rhCBS. CONCLUSIONS: After balancing out patients for hemispheric hypometabolism, we did not confirm worse language or visuospatial deficits in, respectively, lhCBS and rhCBS. However, verbal short-term memory was more impaired in lhCBS, and spatial attention was more impaired in rhCBS. Both of these functions reflect the functional specialization of the left and right fronto-parietal pathways, i.e. of the main loci of neurodegeneration in CBS.

A cognitive marker for Alzheimer disease pathology in primary progressive aphasia? A validation study in the clinical setting.

We validated in the clinical setting a putative clinical marker for a biological diagnosis of primary progressive aphasia (PPA) due to amyloid previously identified in an autopsy cohort and including impaired (score ≤4) digit span (DS) as index of phonological loop dysfunction and broadened criteria for logopenic PPA. In 29 PPA patients with an amyloid-positive (A+) biomarker and 28 PPA patients with an amyloid-negative (A-) biomarker, Receiver Operating Characteristics (ROC) curve analysis showed moderate specificity (71%) but insufficient sensitivity (41%) for the proposed marker. Specificity was particularly poor (58%) for the discrimination between A+ PPA and the A- subgroup with nonfluent PPA. DS may be compromised in both logopenic and nonfluent PPA, whose loci of neurodegeneration lie at the 2 ends of the left fronto-parieto-temporal system that underpins phonology. An Statistical Parametric Mapping (SPM) correlation analysis between DS score and metabolism on brain 18-fluoro-deoxy-glucose positron emission tomography also showed a major contribution of the left frontal cortex to impaired span.

Depressive Pseudodementia with Reversible AD-like Brain Hypometabolism: A Case Report and a Review of the Literature.

Recent European guidelines recommend using brain FDG-PET to differentiate between Alzheimer's disease (AD) and depressive pseudodementia (DP), with specific hypometabolism patterns across the former group, and typically normal or frontal hypometabolism in the latter. We report the case of a 74 years-old man with DP (MMSE 16/30), whose FDG-PET visual rating and semiquantitative analysis closely mimicked the typical AD pattern, showing severe hypometabolism in bilateral precuneus, parietal and temporal lobes, and sparing frontal areas, suggesting the diagnosis of moderate AD. Shortly after starting antidepressant polytherapy, he underwent formal NPS testing, which revealed moderate impairment of episodic memory and mild impairment on executive and visuospatial tests, judged consistent with neurodegenerative dementia and concomitant depression. Over the following two years, he improved dramatically: repeated NPS assessment did not show significant deficits, and FDG-PET showed restoration of cerebral metabolism. The confirmation of PET findings via semiquantitative analysis, and their reversion to normality with antidepressant treatment, proved the non-neurodegenerative origin of the initial AD-like FDG-PET abnormalities. We review similar cases and provide a comprehensive analysis of their implications, concluding that reversible FDG-PET widespread hypometabolism might represent a biomarker of pseudodementia. Therefore, we suggest caution when interpreting FDG-PET scans of depressed patients with cognitive impairment.

Reduced phonemic fluency in progressive supranuclear palsy is due to dysfunction of dominant BA6.

Background: Reduced phonemic fluency is extremely frequent in progressive supranuclear palsy (PSP), but its neural correlate is yet to be defined. Objective: We explored the hypothesis that poor fluency in PSP might be due to neurodegeneration within a dominant frontal circuit known to be involved in speech fluency, including the opercular area, the superior frontal cortex (BA6), and the frontal aslant tract connecting these two regions. Methods: We correlated performance on a letter fluency task (F, A, and S, 60 s for each letter) with brain metabolism as measured with Fluoro-deoxy-glucose Positron Emission Tomography, using Statistical Parametric Mapping, in 31 patients with PSP. Results: Reduced letter fluency was associated with significant hypometabolism at the level of left BA6. Conclusion: Our finding is the first evidence that in PSP, as in other neurogical disorders, poor self-initiated, effortful verbal retrieval appears to be linked to dysfunction of the dominant opercular-aslant-BA6 circuit.

Clinical and metabolic imaging features of late-onset and early-onset posterior cortical atrophy.

BACKGROUND AND PURPOSE: Late-onset (LO) and early-onset (EO) dementia show neurobiological and clinical differences. Clinical and 18 fluoro-deoxy-glucose positron emission tomography (FDG-PET) features of LO and EO posterior cortical atrophy (LO_PCA, EO_PCA), the visual variant of Alzheimer's disease (AD), were compared. LO_PCA patients were also compared with a group of patients with LO typical AD (tAD). METHODS: Thirty-seven LO_PCA patients (onset age ≥ 65 years), 29 EO_PCA patients and 40 tAD patients who all underwent a standard neuropsychological battery were recruited; PCA patients were also assessed for the presence of posterior signs and symptoms. Brain FDG-PET was available in 32 LO_PCA cases, 23 EO_PCA cases and all tAD cases, and their scans were compared with scans from 30 healthy elderly controls. Within the entire PCA sample FDG uptake was also correlated with age at onset as a continuous variable. RESULTS: The main difference between the two PCA groups was a higher prevalence of Bálint-Holmes symptoms in EO cases, which was associated with the presence of severe bilateral occipito-temporo-parietal hypometabolism, whilst LO_PCA patients showed reduction of FDG uptake mainly in the right posterior regions. The latter group also showed mesial temporal hypometabolism, similarly to the tAD group, although with a right rather than left lateralization. Correlation analysis confirmed the association between older age and decreased limbic metabolism and between younger age and decreased left parietal metabolism. CONCLUSIONS: The major involvement of the temporal cortex in LO cases and of the parietal cortex in EO cases reported previously within the AD spectrum holds true also for the visual variant of AD.

The "digital biopsy" in non-small cell lung cancer (NSCLC): a pilot study to predict the PD-L1 status from radiomics features of [18F]FDG PET/CT.

PURPOSE: The present pilot study investigates the putative role of radiomics from [18F]FDG PET/CT scans to predict PD-L1 expression status in non-small cell lung cancer (NSCLC) patients. METHODS: In a retrospective cohort of 265 patients with biopsy-proven NSCLC, 86 with available PD-L1 immunohistochemical (IHC) assessment and [18F]FDG PET/CT scans have been selected to find putative metabolic markers that predict PD-L1 status (< 1%, 1-49%, and ≥ 50% as per tumor proportion score, clone 22C3). Metabolic parameters have been extracted from three different PET/CT scanners (Discovery 600, Discovery IQ, and Discovery MI) and radiomics features were computed with IBSI compliant algorithms on the original image and on images filtered with LLL and HHH coif1 wavelet, obtaining 527 features per tumor. Univariate and multivariate analysis have been performed to compare PD-L1 expression status and selected radiomic features. RESULTS: Of the 86 analyzed cases, 46 (53%) were negative for PD-L1 IHC, 13 (15%) showed low PD-L1 expression (1-49%), and 27 (31%) were strong expressors (≥ 50%). Maximum standardized uptake value (SUVmax) demonstrated a significant ability to discriminate strong expressor cases at univariate analysis (p = 0.032), but failed to discriminate PD-L1 positive patients (PD-L1 ≥ 1%). Three radiomics features appeared the ablest to discriminate strong expressors: (1) a feature representing the average high frequency lesion content in a spherical VOI (p = 0.009); (2) a feature assessing the correlation between adjacent voxels on the high frequency lesion content (p = 0.004); (3) a feature that emphasizes the presence of small zones with similar grey levels inside the lesion (p = 0.003). The tri-variate linear discriminant model combining the three features achieved a sensitivity of 81% and a specificity of 82% in the test. The ability of radiomics to predict PD-L1 positive patients was instead scarce. CONCLUSIONS: Our data indicate a possible role of the [18F]FDG PET radiomics in predicting strong PD-L1 expression; these preliminary data need to be confirmed on larger or single-scanner series.

Learning From Mistakes: Cognitive and Metabolic Correlates of Errors on Picture Naming in the Alzheimer's Disease Spectrum.

BACKGROUND: Analysis of subtypes of picture naming errors produced by patients with Alzheimer's disease (AD) have seldom been investigated yet may clarify the cognitive and neural underpinnings of naming in the AD spectrum. OBJECTIVE: To elucidate the neurocognitive bases of picture naming in AD through a qualitative analysis of errors. METHODS: Over 1000 naming errors produced by 70 patients with amnestic, visuospatial, linguistic, or frontal AD were correlated with general cognitive tests and with distribution of hypometabolism on FDG-PET. RESULTS: Principal component analysis identified 1) a Visual processing factor clustering visuospatial tests and unrecognized stimuli, pure visual errors and visual-semantic errors, associated with right parieto-occipital hypometabolism; 2) a Concept-Lemma factor grouping language tests and anomias, circumlocutions, superordinates, and coordinates, correlated with left basal temporal hypometabolism; 3) a Lemma-Phonology factor including the digit span and phonological errors, linked with left temporo-parietal hypometabolism. Regression of brain metabolism on individual errors showed that errors due to impairment of basic and higher-order processing of object visual attributes, or of their interaction with semantics, were related with bilateral occipital and left occipito-temporal dysfunction. Omissions and superordinates were linked to degradation of broad and basic concepts in the left basal temporal cortex. Semantic-lexical errors derived from faulty semantically- and phonologically-driven lexical retrieval in the left superior and middle temporal gyri. Generation of nonwords was underpinned by impairment of phonology within the left inferior parietal cortex. CONCLUSION: Analysis of individual naming errors allowed to outline a comprehensive anatomo-functional model of picture naming in classical and atypical AD.

Validity of cingulate-precuneus-temporo-parietal hypometabolism for single-subject diagnosis of biomarker-proven atypical variants of Alzheimer's Disease.

The aim of our study was to establish empirically to what extent reduced glucose uptake in the precuneus, posterior cingulate and/or temporo-parietal cortex (PCTP), which is thought to indicate brain amyloidosis in patients with dementia or MCI due to Alzheimer's Disease (AD), permits to distinguish amyloid-positive from amyloid-negative patients with non-classical AD phenotypes at the single-case level. We enrolled 127 neurodegenerative patients with cognitive impairment and a positive (n. 63) or negative (n. 64) amyloid marker (cerebrospinal fluid or amy-PET). Three rating methods of FDG-PET scan were applied: purely qualitative visual interpretation of uptake images (VIUI), and visual reading assisted by a semi-automated and semi-quantitative tool: INLAB, provided by the Italian National Research Council, or Cortex ID Suite, marketed by GE Healthcare. Fourteen scans (11.0%) patients remained unclassified by VIUI or INLAB procedures, therefore, validity values were computed on the remaining 113 cases. The three rating approaches showed good total accuracy (77-78%), good to optimal sensitivity (81-93%), but poorer specificity (62-75%). VIUI showed the highest sensitivity and the lowest specificity, and also the highest proportion of unclassified cases. Cases with asymmetric temporo-parietal hypometabolism and a progressive aphasia or corticobasal clinical profile, in particular, tended to be rated as AD-like, even if biomarkers indicated non-amyloid pathology. Our findings provide formal support to the value of PCTP hypometabolism for single-level diagnosis of amyloid pathophysiology in atypical AD, but also highlight the risk of qualitative assessment to misclassify patients with non-AD PPA or CBS underpinned by asymmetric temporo-parietal hypometabolism.

Clinical Application of a High Sensitivity BGO PET/CT Scanner: Effects of Acquisition Protocols and Reconstruction Parameters on Lesions Quantification.

AIMS: The aim of this retrospective study was to investigate SUVs variability with respect to lesion size, administered dose, and reconstruction algorithm. BACKGROUND: SUVmax and SUVpeak are influenced by technical factors as count statistics and reconstruction algorithms. OBJECTIVE: To fulfill the aim, we evaluated the SUVs variability with respect to lesion size, administered dose, and reconstruction algorithm (ordered - subset expectation maximization plus point spread function option - OSEM+PSF, regularized Bayesian Penalized Likelihood - BPL) in a 5 - rings BGO PET/CT scanner. METHODS: Discovery IQ scanner (GE Healthcare, Milwaukee, Wisconsin, US) was used for list mode acquisition of 25 FDG patients, 12 injected with 3.7 MBq/kg (Standard Dose protocol - SD) and 13 injected with 1.8 MBq/kg (Low Dose protocol - LD). Each acquisition was reconstructed at different time/FOV with both OSEM+PSF algorithm and BPL using seven different beta factors. SUVs were calculated in 70 lesions and analysed in function of time/FOV and Beta. Image quality was evaluated as a coefficient of variation of the liver (CV - liver). RESULTS: SUVs were not considerably affected by time/FOV. However, SUVs were influenced by beta: differences were higher in small lesions (37% for SUVmax, 15% for SUVpeak) compared to larger ones (14% and 6%). CV - liver ranged from 6% with Beta-500 (LD and SD) to 13% with Beta- 200 (LD). CV - liver of BPL with Beta-350 (optimized for clinical practice in our institution) in LD was lower than CV - liver of OSEM+PSF in SD. CONCLUSION: When a high sensitivity 5 - rings BGO PET/CT scanner is used with the same reconstruction algorithm, quantification by means of SUVmax and SUVpeak is a robust standard compared to the activity and scan duration. However, both SUVs and image quality are influenced by reconstruction algorithms and the related parameters should be considered to obtain the best compromise between detectability, quantification, and noise.

Metabolic Parameters as Biomarkers of Response to Immunotherapy and Prognosis in Non-Small Cell Lung Cancer (NSCLC): A Real World Experience.

Immune-checkpoint inhibitors (ICIs) have been proven to have great efficacy in non-small cell lung cancer (NSCLC) as single agents or in combination therapy, being capable to induce deep and durable remission. However, severe adverse events may occur and about 40% of patients do not benefit from the treatment. Predictive factors of response to ICIs are needed in order to customize treatment. The aim of this study is to evaluate the correlation between quantitative positron emission tomography (PET) parameters defined before starting ICI therapy and responses to treatment and patient outcome. We retrospectively analyzed 92 NSCLC patients treated with nivolumab, pembrolizumab or atezolizumab. Basal PET/computed tomography (CT) scan parameters (whole-body metabolic tumor volume-wMTV, total lesion glycolysis-wTLG, higher standardized uptake volume maximum and mean-SUVmax and SUVmean) were calculated for each patient and correlated with outcomes. Patients who achieved disease control (complete response + partial response + stable disease) had significantly lower MTV median values than patients who had not (progressive disease) (77 vs. 160.2, p = 0.039). Furthermore, patients with MTV and TLG values lower than the median values had improved OS compared to patients with higher MTV and TLG (p = 0.03 and 0.05, respectively). No relation was found between the other parameters and outcome. In conclusion, baseline metabolic tumor burden, measured with MTV, might be an independent predictor of treatment response to ICI and a prognostic biomarker in NSCLC patients.

Temporal lobe dysfunction in late-onset epilepsy of unknown origin.

OBJECTIVE: Epilepsy with onset in the adulthood is an increasing health problem, due to the progressive aging of the worldwide population. Whether the causes remain undetermined, the disease is defined as Late-Onset Epilepsy of Unknown origin (LOEU). The aim of this study was to evaluate the semiological, electroencephalographic, metabolic, and neuropsychological features of LOEU. METHODS: We selected patients with late-onset epilepsy (LOE) (≥55 years), whose causes of the disease have been excluded with a deep clinical-instrumental characterization, including brain MRI, EEG, 18F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET), and neuropsychological assessment. RESULTS: Twenty-three LOEU cases were retrospectively recruited. Half presented focal-onset seizures (FOS), the others focal to bilateral tonic-clonic seizures (FBTCS). All demonstrated a mild phenotype, with no recurrence of seizures on single antiseizure treatment at prolonged follow-up. Brain MRI scans were normal in 12 patients (52.3%) and showed nonspecific gliosis or mild atrophy in ten (43.5%); hippocampal sclerosis (HS) was observed in one. In 17/23 (73.9%), the EEG showed slow and/or epileptiform activity of the temporal areas. Brain FDG-PET revealed temporal lobe hypometabolism, mostly ipsilateral to EEG abnormal activity, or multifocal temporal and extra-temporal (cortical, subcortical and subtentorial) clusters of hypometabolism. The neuropsychological analysis demonstrated three different profiles: normal (43.5%), with focal deficits (39.1%) or mild multidomain impairment (17.4%). SIGNIFICANCE: Late-Onset Epilepsy of Unknown origin can present as FOS or FBTCS, both with good prognosis. The application of metabolic imaging and neurophysiology techniques in these patients points to the dysfunction of the temporal structures, whose role in the pathogenetic process of the disease remains to be clarified.

A Metabolic Imaging Study of Lexical and Phonological Naming Errors in Alzheimer Disease.

Patients with Alzheimer disease (AD) produce a variety of errors on confrontation naming that indicate multiple loci of impairment along the naming process in this disease. We correlated brain hypometabolism, measured with 18fluoro-deoxy-glucose positron emission tomography, with semantic and formal errors, as well as nonwords deriving from phonological errors produced in a picture-naming test by 63 patients with AD. Findings suggest that neurodegeneration leads to: (1) phonemic errors, by interfering with phonological short-term memory, or with control over retrieval of phonological or prearticulatory representations, within the left supramarginal gyrus; (2) semantic errors, by disrupting general semantic or visual-semantic representations at the level of the left posterior middle and inferior occipitotemporal cortex, respectively; (3) formal errors, by damaging the lexical-phonological output interface in the left mid-anterior segment of middle and superior temporal gyri. This topography of semantic-lexical-phonological steps of naming is in substantial agreement with dual-stream neurocognitive models of word generation.

Respiratory Gating and the Performance of PET/CT in Pulmonary Lesions.

BACKGROUND: Motion artifacts related to the patient's breathing can be the cause of underestimation of the lesion uptake and can lead to missing of small lung lesions. The respiratory gating (RG) technology has demonstrated a significant increase in image quality. OBJECTIVE: The aim of this paper was to evaluate the advantages of RG technique on PET/CT performance in lung lesions. The impact of 4D-PET/CT on diagnosis (metabolic characterization), staging and re-staging lung cancer was also assessed, including its application for radiotherapy planning. Finally, new technologies for respiratory motion management were also discussed. METHODS: A comprehensive electronic search of the literature was performed by using Medline database (PubMed) searching "PET/CT", "gated" and "lung". Original articles, review articles, and editorials published in the last 10 years were selected, included and critically reviewed in order to select relevant articles. RESULTS: Many papers compared Standardized Uptake Value (SUV) in gated and ungated PET studies showing an increase in SUV of gated images, particularly for the small lesions located in medium and lower lung. In addition, other features as Metabolic Tumor Volume (MTV), Total Lesion Glycolysis (TLG) and textural-features presented differences when obtained from gated and ungated PET acquisitions. Besides the increase in quantification, gating techniques can determine an increase in the diagnostic accuracy of PET/CT. Gated PET/CT was evaluated for lung cancer staging, therapy response assessment and for radiation therapy planning. CONCLUSION: New technologies able to track the motion of organs lesion directly from raw PET data, can reduce or definitively solve problems (i.e.: extended acquisition time, radiation exposure) currently limiting the use of gated PET/CT in clinical routine.

Combining positron emission tomography/computed tomography, radiomics, and sentinel lymph node mapping for nodal staging of endometrial cancer patients.

OBJECTIVE: To evaluate the combination of positron emission tomography/computed tomography (PET/CT) and sentinel lymph node (SLN) biopsy in women with apparent early-stage endometrial carcinoma. The correlation between radiomics features extracted from PET images of the primary tumor and the presence of nodal metastases was also analyzed. METHODS: From November 2006 to March 2019, 167 patients with endometrial cancer were included. All women underwent PET/CT and surgical staging: 60/167 underwent systematic lymphadenectomy (Group 1) while, more recently, 107/167 underwent SLN biopsy (Group 2) with technetium-99m +blue dye or indocyanine green. Histology was used as standard reference. PET endometrial lesions were segmented (n=98); 167 radiomics features were computed inside tumor contours using standard Image Biomarker Standardization Initiative (IBSI) methods. Radiomics features associated with lymph node metastases were identified (Mann-Whitney test) in the training group (A); receiver operating characteristic (ROC) curves, area under the curve (AUC) values were computed and optimal cut-off (Youden index) were assessed in the test group (B). RESULTS: In Group 1, eight patients had nodal metastases (13%): seven correctly ridentified by PET/CT true-positive with one false-negative case. In Group 2, 27 patients (25%) had nodal metastases: 13 true-positive and 14 false-negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for pelvic nodal metastases were 87%, 94%, 93%, 70%, and 98% in Group 1 and 48%, 97%, 85%, 87%, and 85% in Group 2, respectively. On radiomics analysis a significant association was found between the presence of lymph node metastases and 64 features. Volume-density, a measurement of shape irregularity, was the most predictive feature (p=0001, AUC=0,77, cut-off 0.35). When testing cut-off in Group B to discriminate metastatic tumors, PET false-negative findings were reduced from 14 to 8 (-43%). CONCLUSIONS: PET/CT demonstrated high specificity in detecting nodal metastases. SLN and histologic ultrastaging increased false-negative PET/CT findings, reducing the sensitivity of the technique. PET radiomics features of the primary tumor seem promising for predicting the presence of nodal metastases not detected by visual analysis.

Role of 18 F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in malignant ovarian germ cell tumors: a single-center experience with long term follow-up.

INTRODUCTION: 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a diagnostic tool widely used in oncology, but to date there are no established recommendations for its use in malignant ovarian germ cell tumors. The aim of this study was to evaluate the role of 18F-FDG PET/CT in the clinical management of patients with malignant ovarian germ cell tumors. METHODS: This was a retrospective review of 18F-FDG PET/CT scans performed in patients diagnosed with malignant ovarian germ cell tumors treated at the gynecology department of San Gerardo Hospital (Monza, Italy) from June 2006 to December 2016. Data collected included clinical history, radiological, biochemical and pathological evaluation, treatment, follow-up, outcome, and clinical indication for the PET/CT scan. PET/CT findings were categorized as negative/normal (no abnormal FDG uptake or physiological uptake), positive/abnormal (FDG uptake considered to indicate active germ cell malignancy), or equivocal (FDG uptake of uncertain significance, not clearly correlated to neoplastic disease). RESULTS: A total of 69 PET/CT scans in 37 patients were evaluated. The mean age at diagnosis was 25 years (range 20-48). The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage I (22/37) disease and had a diagnosis of dysgerminomas (18/37). Imaging indications were initial staging before treatment (4/69, 6%), staging after inadequate staging surgery (24/69, 35%), restaging after adjuvant chemotherapy (17/69, 25%), relapse suspect (9/69, 13%), and follow-up (15/69, 21%). Pathology confirmation of PET/CT results was available in 28/69 (40.5%) studies. All negative PET/CT (15/28) cases were confirmed with laparoscopy as true negative; among 13/28 positive PET cases, histopathology confirmed 7 (54%) as true positive and 6 (46%) as false positive (5 inflammatory and 1 mature teratoma implants). Patient-based analysis showed 100% sensitivity, 71% specificity, 54% positive predictive value, 100% negative predictive value, and 79% accuracy. Clinical follow-up was available in 41 (59.4%) of 69 PET/CT images: 28/41 studies were negative and 13/41 positive. A mean follow-up of 28 months (median 15, range 5-102) confirmed negative PET/CT studies. A total of 13 positive PET/CT patients underwent chemotherapy with subsequent evidence of disease response. DISCUSSION: PET/CT in malignant ovarian germ cell tumors was mainly performed for staging after inadequate staging surgery or for restaging after adjuvant chemotherapy. PET/CT was associated with high sensitivity and negative predictive value.

18F-FDG PET/CT in a Case of Metastatic Breast Cancer to the Vulva.

A 56-year-old woman, previously treated for breast cancer, presented to gynecologists with a lump of the left labium major of the vulva. The FDG pattern resembled as a cIV stage vulvar cancer, whereas biopsy indicated metastases from breast cancer. Metastatic disease to the vulva is particularly uncommon, representing 5% to 8% of all vulvar cancer lesions. However, gynecological uptakes, including vulvar site, have to be kept in mind as a possible site of metastatic lesions from breast cancer.

Treatment response assessment in [18F]FDG-PET/CT oncology scans: Impact of count statistics variation and reconstruction protocol.

PURPOSE: To investigate influences of reconstruction algorithms and count statistics variation on quantification and treatment response assessment in cancer patients, by using a large field of view-FOV scanner. METHODS: 54 cancer patients underwent PET/CT scan: 1) at baseline: 1.5 min/FOV, reconstructed by ordered-subset expectation maximization + point-spread-function-OSEM-PSF and bayesian penalised-likelihood-BPL algorithm 2) at restaging: 2 min/FOV, reconstructed also at 1.5 and 1 min/FOV, using OSEM-PSF and BPL. SUL (lean-body mass SUV) peak and max were measured for each target-lesion (n = 59). Differences in quantification obtained from datasets with different reconstruction algorithms and different time/FOV were evaluated. For any pair of PET datasets, metabolic response was assessed by using SULpeak, with a threshold of 30% in variation considered as significant. RESULTS: Both at baseline and restaging, SULpeak and max values were higher in BPL reconstructions than in OSEM-PSF (p < 0.0001). SULpeak at different time/FOV reconstructions showed no statistically significant differences both with OSEM-PSF and BPL; SULmax depended on acquisition time (p < 0.05). In 56/59 lesions (95%) therapy response was concordant regardless count statistics variation and reconstruction algorithm; 2/59 (3%) showed different responses according to count statistics, both for OSEM-PSF and BPL; in 1/59 lesion (2%) response was different depending on reconstruction algorithm used. CONCLUSIONS: BPL provided higher SULpeak and max than OSEM-PSF. With a large FOV/high sensitivity scanner, variation of time/FOV in restaging PET scans gave stable and reproducible results in terms of SULpeak, both for OSEM-PSF and BPL. Thus, metabolic response defined by SULpeak variation proved to be quite independent from count statistics.