[68Ga]DOTATOC PET-derived radiomics to predict genetic background of head and neck paragangliomas: a pilot investigation.

PURPOSE: To investigate the [68Ga]DOTATOC PET radiomic profile of head and neck paragangliomas (HNPGLs) and identify radiomic characteristics useful as predictors of succinate dehydrogenase genes (SDHx) pathogenic variants. METHODS: Sporadic and SDHx HNPGL patients, who underwent [68Ga]DOTATOC PET/CT, were retrospectively included. HNPGLs were analyzed using LIFEx software, and extracted features were harmonized to correct for batch effects and confronted testing for multiple comparison. Stepwise discriminant analysis was conducted to remove redundancy and identify best discriminating features. ROC analysis was used to define optimal cut-offs. Multivariate decision-tree analysis was performed using CHAID method. RESULTS: 34 patients harboring 60 HNPGLs (51 SDHx in 25 patients) were included. Three sporadic and nine SDHx HNPGLs were metastatic. At stepwise discriminant analysis, both GLSZM-Zone Size Non-Uniformity (ZSNU, reflecting tumor heterogeneity) and IB-TLSRE (total lesion somatostatin receptor expression) were independent predictors of genetic status, with 96.4% of lesions and 91.6% of patients correctly classified after cross validation (p < 0.001). Among non-metastatic patients, GLSZM-ZSNU and IB-TLSRE were significantly higher in sporadic than SDHx HNPGLs (p < 0.001). No differences were revealed in metastatic patients. Decision-tree analysis highlights multifocality and IB-TLSRE as useful variables, correctly identifying 6/9 sporadic and 24/25 SDHx patients. Model failed to classify one SDHA and three sporadic patients (2 metastatic). CONCLUSION: Radiomics features GLSZM-ZSNU and IB-TLSRE appear to reflect HNPGLs SDHx status and tumor behavior (metastatic vs. non-metastatic). If validated, especially IB-TLSRE might represent a simple and time-efficient radiomic index for SDHx variants early screening and prediction of tumor behavior in HNPGL cases.

Molecular imaging and related therapeutic options for medullary thyroid carcinoma: state of the art and future opportunities.

Due to its rarity and non-specific clinical presentation, accurate diagnosis, and optimal therapeutic strategy of medullary thyroid carcinoma (MTC) remain challenging. Molecular imaging provides valuable tools for early disease detection, monitoring treatment response, and guiding personalized therapies. By enabling the visualization of molecular and cellular processes, these techniques contribute to a deeper understanding of disease mechanisms and the development of more effective clinical interventions. Different nuclear imaging techniques have been studied for assessing MTC, and among them, PET/CT utilizing multiple radiotracers has emerged as the most effective imaging method in clinical practice. This review aims to provide a comprehensive summary of the current use of advanced molecular imaging modalities, with a particular focus on PET/CT, for the management of patients with MTC. It aims to guide physicians towards a rationale for the use of molecular imaging also including theranostic approaches and novel therapeutical opportunities. Overall, we emphasize the evolving role of nuclear medicine in MTC. The integration of diagnostics and therapeutics by in vivo molecular imaging represents a major opportunity to personalize treatment for individual patients, with targeted radionuclide therapy being one representative example.

Texture analysis of 18F-FDG PET/CT and CECT: Prediction of refractoriness of Hodgkin lymphoma with mediastinal bulk involvement.

To recognize patients at high risk of refractory disease, the identification of novel prognostic parameters improving stratification of newly diagnosed Hodgkin Lymphoma (HL) is still needed. This study investigates the potential value of metabolic and texture features, extracted from baseline 18F-FDG Positron Emission Tomography/Computed Tomography (PET) and Contrast-Enhanced Computed Tomography scan (CECT), together with clinical data, in predicting first-line therapy refractoriness (R) of classical HL (cHL) with mediastinal bulk involvement. We reviewed 69 cHL patients who underwent staging PET and CECT. Lesion segmentation and texture parameter extraction were performed using the freeware software LIFEx 6.3. The prognostic significance of clinical and imaging features was evaluated in relation to the development of refractory disease. Receiver operating characteristic curve, Cox proportional hazard regression and Kaplan-Meier analyses were performed to examine the potential independent predictors and to evaluate their prognostic value. Among clinical characteristics, only stage according to the German Hodgkin Group (GHSG) classification system significantly differed between R and not-R. Among CECT variables, only parameters derived from second order matrices (gray-level co-occurrence matrix (GLCM) and gray-level run length matrix (GLRLM) demonstrated significant prognostic power. Among PET variables, SUVmean, several variables derived from first (histograms, shape), and second order analyses (GLCM, GLRLM, NGLDM) exhibited significant predictive power. Such variables obtained accuracies greater than 70% at receiver operating characteristic analysis and their PFS curves resulted statistically significant in predicting refractoriness. At multivariate analysis, only HISTO_EntropyPET extracted from PET (HISTO_EntropyPET ) and GHSG stage resulted as significant independent predictors. Their combination identified 4 patient groups with significantly different PFS curves, with worst prognosis in patients with higher HISTO_EntropyPET values, regardless of the stage. Imaging radiomics may provide a reference for prognostic evaluation of patients with mediastinal bulky cHL. The best prognostic value in the prediction of R versus not-R disease was reached by combining HISTO_EntropyPET with GHSG stage.

Plasma neurofilament light chain predicts Alzheimer's disease in patients with subjective cognitive decline and mild cognitive impairment: A cross-sectional and longitudinal study.

BACKGROUND AND PURPOSE: We aimed to evaluate the accuracy of plasma neurofilament light chain (NfL) in predicting Alzheimer's disease (AD) and the progression of cognitive decline in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHODS: This longitudinal cohort study involved 140 patients (45 with SCD, 73 with MCI, and 22 with AD dementia [AD-D]) who underwent plasma NfL and AD biomarker assessments (cerebrospinal fluid, amyloid positron emission tomography [PET], and 18 F-fluorodeoxyglucose-PET) at baseline. The patients were rated according to the amyloid/tau/neurodegeneration (A/T/N) system and followed up for a mean time of 2.72 ± 0.95 years to detect progression from SCD to MCI and from MCI to AD. Forty-eight patients (19 SCD, 29 MCI) also underwent plasma NfL measurements 2 years after baseline. RESULTS: At baseline, plasma NfL detected patients with biomarker profiles consistent with AD (A+/T+/N+ or A+/T+/N-) with high accuracy (area under the curve [AUC] 0.82). We identified cut-off values of 19.45 pg/mL for SCD and 20.45 pg/mL for MCI. During follow-up, nine SCD patients progressed to MCI (progressive SCD [p-SCD]), and 14 MCI patients developed AD dementia (progressive MCI [p-MCI]). The previously identified cut-off values provided good accuracy in identifying p-SCD (80% [95% confidence interval 65.69: 94.31]). The rate of NfL change was higher in p-MCI (3.52 ± 4.06 pg/mL) compared to non-progressive SCD (0.81 ± 1.25 pg/mL) and non-progressive MCI (-0.13 ± 3.24 pg/mL) patients. A rate of change lower than 1.64 pg/mL per year accurately excluded progression from MCI to AD (AUC 0.954). CONCLUSION: Plasma NfL concentration and change over time may be a reliable, non-invasive tool to detect AD and the progression of cognitive decline at the earliest stages of the disease.

The role of plasma neurofilament light chain and glial fibrillary acidic protein in subjective cognitive decline and mild cognitive impairment.

INTRODUCTION AND AIM: NfL and GFAP are promising blood-based biomarkers for Alzheimer's disease. However, few studies have explored plasma GFAP in the prodromal and preclinical stages of AD. In our cross-sectional study, our aim is to investigate the role of these biomarkers in the earliest stages of AD. MATERIALS AND METHODS: We enrolled 40 patients (11 SCD, 21 MCI, 8 AD dementia). All patients underwent neurological and neuropsychological examinations, analysis of CSF biomarkers (Aß42, Aß42/Aß40, p-tau, t-tau), Apolipoprotein E (APOE) genotype analysis and measurement of plasma GFAP and NfL concentrations. Patients were categorized according to the ATN system as follows: normal AD biomarkers (NB), carriers of non-Alzheimer's pathology (non-AD), prodromal AD, or AD with dementia (AD-D). RESULTS: GFAP was lower in NB compared to prodromal AD (p = 0.003, d = 1.463) and AD-D (p = 0.002, d = 1.695). NfL was lower in NB patients than in AD-D (p = 0.011, d = 1.474). NfL demonstrated fair accuracy (AUC = 0.718) in differentiating between NB and prodromal AD, with a cut-off value of 11.65 pg/mL. GFAP showed excellent accuracy in differentiating NB from prodromal AD (AUC = 0.901) with a cut-off level of 198.13 pg/mL. CONCLUSIONS: GFAP exhibited excellent accuracy in distinguishing patients with normal CSF biomarkers from those with prodromal AD. Our results support the use of this peripheral biomarker for detecting AD in patients with subjective and objective cognitive decline.

FDG PET in the differential diagnosis of degenerative parkinsonian disorders: usefulness of voxel-based analysis in clinical practice.

BACKGROUND: The early differential diagnosis among neurodegenerative parkinsonian disorders becomes essential to set up the correct clinical-therapeutic approach. The increased utilization of [18F] fluoro-deoxy-glucose positron emission tomography (FDG PET) and the pressure for cost-effectiveness request a systematic evaluation and a validation of its utility in clinical practice. This retrospective study aims to consider the contribution, in terms of increasing accuracy and increasing diagnostic confidence, of voxel-based FDG PET analyses in the differential diagnosis of these disorders, including Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and cortico-basal syndrome. METHOD: Eighty-three subjects with a clinically confirmed diagnosis of degenerative parkinsonian disorders who underwent FDG brain PET/CT were selected. A voxel-based analysis was set up using statistical parametric mapping (SPM) on MATLAB to produce maps of brain hypometabolism and relative hypermetabolism. Four nuclear physicians (two expert and two not expert), blinded to the patients' symptoms, other physicians' evaluations, and final clinical diagnosis, independently evaluated all data by visual assessment and by adopting metabolic maps. RESULTS: In not-expert evaluators, the support of both hypometabolism and hypermetabolism maps results in a significant increase in diagnostic accuracy as well as clinical confidence. In expert evaluators, the increase in accuracy and in diagnostic confidence is mainly supported by hypometabolism maps alone. CONCLUSIONS: In this study, we demonstrated the additional value of combining voxel-based analyses with qualitative assessment of brain PET images. Moreover, maps of relative hypermetabolism can also make their contribution in clinical practice, particularly for less experienced evaluators.

Cerebral amyloid load determination in a clinical setting: interpretation of amyloid biomarker discordances aided by tau and neurodegeneration measurements.

BACKGROUND: Alzheimer's disease (AD) diagnosis can be hindered by amyloid biomarkers discordances. OBJECTIVE: We aim to interpret discordances between amyloid positron emission tomography (Amy-PET) and cerebrospinal fluid (CSF) (Aß42 and Aß42/40), using Amy-PET semiquantitative analysis, [18F]fluorodeoxyglucose (FDG)-PET pattern, and CSF assays. METHOD: Thirty-six subjects with dementia or mild cognitive impairment, assessed by neuropsychological tests, structural and functional imaging, and CSF assays (Aß42, Aß42/40, p-tau, t-tau), were retrospectively examined. Amy-PET and FDG-PET scans were analyzed by visual assessment and voxel-based analysis. SUVR were calculated on Amy-PET scans. RESULTS: Groups were defined basing on the agreement among CSF Aß42 (A), CSF Aß42/40 Ratio (R), and Amy-PET (P) dichotomic results ( ±). In discordant groups, CSF assays, Amy-PET semiquantification, and FDG-PET patterns supported the diagnosis suggested by any two agreeing amyloid biomarkers. In groups with discordant CSF Aß42, the ratio always agrees with Amy-PET results, solving both false-negative and false-positive Aß42 results, with Aß42 levels close to the cut-off in A + R-P- subjects. The A + R + P- group presented high amyloid deposition in relevant areas, such as precuneus, posterior cingulate cortex (PCC) and dorsolateral frontal inferior cortex at semiquantitative analysis. CONCLUSION: The amyloid discordant cases could be overcome by combining CSF Aß42, CSF ratio, and Amy-PET results. The concordance of any 2 out of the 3 biomarkers seems to reveal the remaining one as a false result. A cut-off point review could avoid CSF Aß42 false-negative results. The regional semiquantitative Amy-PET analysis in AD areas, such as precuneus and PCC, could increase the accuracy in AD diagnosis.

Validation of FDG-PET datasets of normal controls for the extraction of SPM-based brain metabolism maps.

PURPOSE: An appropriate healthy control dataset is mandatory to achieve good performance in voxel-wise analyses. We aimed at evaluating [18F]FDG PET brain datasets of healthy controls (HC), based on publicly available data, for the extraction of voxel-based brain metabolism maps at the single-subject level. METHODS: Selection of HC images was based on visual rating, after Cook's distance and jack-knife analyses, to exclude artefacts and/or outliers. The performance of these HC datasets (ADNI-HC and AIMN-HC) to extract hypometabolism patterns in single patients was tested in comparison with the standard reference HC dataset (HSR-HC) by means of Dice score analysis. We evaluated the performance and comparability of the different HC datasets in the assessment of single-subject SPM-based hypometabolism in three independent cohorts of patients, namely, ADD, bvFTD and DLB. RESULTS: Two-step Cook's distance analysis and the subsequent jack-knife analysis resulted in the selection of n = 125 subjects from the AIMN-HC dataset and n = 75 subjects from the ADNI-HC dataset. The average concordance between SPM hypometabolism t-maps in the three patient cohorts, as obtained with the new datasets and compared to the HSR-HC standard reference dataset, was 0.87 for the AIMN-HC dataset and 0.83 for the ADNI-HC dataset. Pattern expression analysis revealed high overall accuracy (> 80%) of the SPM t-map classification according to different statistical thresholds and sample sizes. CONCLUSIONS: The applied procedures ensure validity of these HC datasets for the single-subject estimation of brain metabolism using voxel-wise comparisons. These well-selected HC datasets are ready-to-use in research and clinical settings.

Imaging biomarkers in the diagnosis of salivary gland tumors: the value of lesion/parenchyma ratio of perfusion-MR pharmacokinetic parameters.

BACKGROUND AND PURPOSE: Morphologic magnetic resonance imaging (MRI) for characterization of salivary gland tumors has limited utility, and the use of perfusion MRI data in the clinical setting is controversial. We examined the potential of tissue-normalized dynamic contrast-enhanced (DCE) MRI pharmacokinetic parameters of salivary gland tumors as imaging biomarkers for characterization and differentiation between benign and malignant lesions. MATERIALS AND METHODS: DCE-MR images acquired from 60 patients with parotid and submandibular gland tumors were retrospectively reviewed. Pharmacokinetic parameters as transfer constant (Ktrans), rate constant (Kep), extracellular space volume (Ve), fractional plasma volume (Vp), and AEC (area of all times enhancement curve) were measured on both the lesion and the normal contralateral salivary gland parenchyma. Lesion/parenchyma ratio (L/P) for each parameter was calculated. RESULTS: Five groups of lesions were identified (reference: histopathology): pleomorphic adenomas(n = 20), Warthin tumors(n = 16), other benign entities(n = 4), non-Hodgkin lymphomas(n = 4), and malignancies(n = 16). Significant differences were seen for mean values of L/PKtrans (higher in malignancies), L/PKep (lower in adenomas than Warthin tumors), L/PVe (lower in Warthin tumors and lymphomas), L/PVp (higher in Warthin tumors and malignancies than adenomas), and L/PAEC (higher in malignancies). Significant differences were found between benign and malignant (non-lymphoproliferative) lesions in mean value of L/PKtrans (0.485 and 1.581), L/PVp (1.288 and 2.834), and L/PAEC (0.682 and 1.910). ROC analysis demonstrated the highest AUC (0.96) for L/PAEC, with sensitivity and specificity for malignancy of 93.8% and 97.5% (cutoff value = 1.038). CONCLUSION: Lesion/parenchyma ratio of DCE-MRI pharmacokinetic data could be helpful for recognizing the principal types of salivary gland tumors; L/PAEC seems a valuable biomarker for differentiating benign from malignant tumors.

Gastrointestinal neuroendocrine neoplasms (GI-NENs): hot topics in morphological, functional, and prognostic imaging.

Neuroendocrine neoplasms (NENs) are heterogeneous tumours with a common phenotype descended from the diffuse endocrine system. NENs are found nearly anywhere in the body but the most frequent location is the gastrointestinal tract. Gastrointestinal neuroendocrine neoplasms (GI-NENs) are rather uncommon, representing around 2% of all gastrointestinal tumours and 20-30% of all primary neoplasms of the small bowel. GI-NENs have various clinical manifestations due to the different substances they can produce; some of these tumours appear to be associated with familial syndromes, such as multiple endocrine neoplasm and neurofibromatosis type 1. The current WHO classification (2019) divides NENs into three major categories: well-differentiated NENs, poorly differentiated NENs, and mixed neuroendocrine-non-neuroendocrine neoplasms. The diagnosis, localization, and staging of GI-NENs include morphology and functional imaging, above all contrast-enhanced computed tomography (CECT), and in the field of nuclear medicine imaging, a key role is played by 68Ga-labelled-somatostatin analogues (68Ga-DOTA-peptides) positron emission tomography/computed tomography (PET/TC). In this review of recent literature, we described the objectives of morphological/functional imaging and potential future possibilities of prognostic imaging in the assessment of GI-NENs.

Behavioural disorders in Alzheimer's disease: the descriptive and predictive role of brain 18 F-fluorodesoxyglucose-positron emission tomography.

BACKGROUND: Alzheimer's disease (AD) has a high incidence in the elderly. Besides cognitive disorders, patients may also develop behavioural and psychological symptoms of dementia (BPSD), which can be particularly disabling for patients and families. BPSD encompass a wide range of symptoms, among which psychotic symptoms and disruptive behaviours often prompt the first related hospitalization and request for family support. The aetiological mechanism of BPSD has not yet been clarified, and no predictive or risk factors have been identified. The main objectives of our study are to describe the frequency of aggression/agitation and psychotic symptoms, defined 'positive BPSD', in a cohort of 60 AD patients, identify areas of the brain involved in behavioural symptomatology through brain 18 F-fluorodesoxyglucose-positron emission tomography (FDG-PET), and investigate a potential predictive role of brain FDG-PET in BPSD development. METHODS: A cohort of 60 AD patients was retrospectively enrolled and regularly followed for at least 3 years. Each subject underwent brain FDG-PET at the time of diagnosis. Patients were divided into three groups based on the presence of behavioural disturbances: present, absent, and developed later. RESULTS: Of the 60 AD patients in the cohort, 52% had positive BPSD: 17 at baseline and 14 during the 3-year follow-up. FDG-PET identified an association between hypometabolism in the bilateral temporal lobes and the presence of BPSD, and showed initial hypometabolism in the postero-temporal lobes 3 years before symptom onset. CONCLUSIONS: Positive BPSD are frequently manifested in AD. Our study identified the temporal lobes as the neurobiological substrate of positive BPSD and FDG-PET as a potential instument to predict their developement. Temporal lobes are involved in processing facial expression and recognizing emotions; an impairment of these functions could cause delusions and agitated/aggressive behaviour. To confirm the potential predictive role of FDG-PET in the onset of BPSD in AD, further studies are needed.

Metastatic intracranial solitary fibrous tumors/hemangiopericytomas: description of two cases with radically different behaviors and review of the literature.

Solitary fibrous tumor/hemangiopericytoma with primary tumor location in the central nervous system accounts for less than 1% of all central nervous system tumors. Despite the relatively indolent clinical course, extracranial metastases are reported in 28% of cases. In recent years, NAB2-STAT6 gene fusion has been recognized as the pathognomonic molecular feature of solitary fibrous tumor/hemangiopericytoma and STAT6 immunohistochemistry has been shown to be a sensitive and specific surrogate for the identification of the gene fusion in these patients. Here we report two cases of patients who experienced occurrence of diffuse extracranial metastases several years after successful surgery for an intracranial solitary fibrous tumor/hemangiopericytoma. In the first patient, the metastases had maintained similar histological features to the primary tumor; in contrast, in the second case, a dedifferentiation occurred with loss of expression of CD34 and Bcl-2. These different histological features were associated with radically different behaviors. Whereas the first case experienced an indolent course of the disease, the second patient had a rapid disease progression and deterioration of clinical conditions. The molecular imaging findings in these two cases and the role of functional imaging for tumor detection, disease staging and monitoring in this rare cancer are also discussed. Recurrences and metastases maintained high expression of somatostatin receptors confirmed by somatostatin receptor imaging in the first case. In contrast, in the second patient, the abrupt transition into a highly aggressive form was associated with the absence of somatostatin receptors at 111In Pentetreotide scan and intense hypermetabolism at 18F-FDG PET.

Diagnostic imaging of typical lung carcinoids: relationship between MDCT, 111In-Octreoscan and 18F-FDG-PET imaging features with Ki-67 index.

AIMS: This study analyses the capability of contrast-enhanced multi-detector computed tomography (MDCT) and spectrum of molecular imaging to characterize typical carcinoids (TCs) of lung and their relationship with Ki-67 index. MATERIALS AND METHODS: We analysed 68 patients with histological diagnosis of pulmonary TC, which underwent both MDCT and nuclear molecular imaging (somatostatin receptor scintigraphy/SPECT with 111In-pentetreotide and 18F-FDG-PET/CT) at staging evaluation before surgery. The MDCT scan was reviewed for the following features: size, margins, contrast enhancement, presence of calcifications, bronchial obstruction, lymph nodes and metastases. In 111In-pentetreotide SPECT, tumour/non-tumour ratio was measured at 4- and 24-h post-injection and the per cent difference was calculated (T/NT%). FDG uptake was measured as the ratio between lesion SUVmax and liver SUVmean (SUV ratio). All imaging features were correlated between them and with Ki-67 index. RESULTS: Forty-four of the 68 lesions (65%) were in the right lung. In MDCT, scan lesions appeared as a well-defined nodule in 44 patients (65%) and irregular mass in 24 patients (35%). Contrast intense enhancement was present in 53 patients (78%), calcifications in 20 patients (29%) and bronchial obstruction in 24 patients (35%). Lymph nodes and metastasis were present in 13 (19%) and 15 (22%) patients. Ki-67 index was negatively correlated with T/NT% and positively with SUV ratio; T/NT% and SUV ratio were inversely correlated. The presence of irregular margins and metastases was negatively related to T/NT%. The presence of a mass, irregular margins, bronchial obstruction, lymph nodes and metastasis was positively related to higher SUV ratio. The presence of irregular margins, bronchial obstruction, lymph nodes and metastases was significantly correlated with a higher grade of Ki-67 index. CONCLUSIONS: MDCT and nuclear molecular imaging are important to characterize lung TCs. The majority of TCs appear as a well-defined nodule generally not associated with extra-thorax signs. We found a significant correlation between some MDCT aspects, nuclear medicine features and Ki-67 index. The association of MDCT and nuclear medicine imaging may be useful in predicting proliferative activity and prognosis of lung TCs.

Electronic processing of digital panoramic radiography for the detection of apical periodontitis.

INTRODUCTION: This study aimed to evaluate the accuracy of both digital complete and small portion of panoramic radiography (PAN) in the detection of clinically/surgically confirmed asymptomatic apical periodontitis (AP) lesions with and without endodontic treatment. METHODS: A total of 480 patients/teeth including 120 AP with and without endodontic treatment, and 120 healthy periapex with and without endodontic treatment were detected via CBCT using the periapical index system. Each diseased and healthy patient underwent PAN first and a CBCT scan within 40 days. All 480 cases were assessed by four different methods, as follows: complete PAN with clinical examination of each tooth available and not available, respectively, and small portion of PAN in which a root with crown and root without crown were displayed, respectively. Periapical index system was also used to assess AP by PAN. Accuracy for both complete and small portion of PAN with respect to CBCT was analyzed. RESULTS: The overall accuracy of the four methods for teeth with endodontic treatment (73.4) was higher than teeth without endodontic treatment (66.6). Accuracy of complete PAN and portion of PAN was 71.3 and 68.7, respectively. As regards teeth without endodontic treatment, accuracy was higher for complete PAN in the upper/lower incisive area and for small portion of PAN in the upper molar area. No difference was found in teeth with endodontic treatment. CONCLUSION: Complete and small portion of PAN showed greater accuracy in the upper/lower incisive area and upper molar area of untreated teeth, respectively, whereas no difference was found in treated teeth.

Primary Progressive Aphasia: Natural History in an Italian Cohort.

BACKGROUND/AIMS: Few longitudinal studies have explored the progression of cognitive and functional impairment of patients with primary progressive aphasia (PPA). The aims of the study were to describe the clinical, neuroimaging, and genetic features of a cohort of 68 PPA patients, and to outline the natural history of the disease. MATERIALS AND METHODS: A sample of 23 patients with the logopenic variant, 26 with the nonfluent/agrammatic variant, and 19 with the semantic variant was retrospectively collected and followed-up for a maximum of 6 years. Clinical-neuropsychological assessment, fluorodeoxyglucose positron emission tomographic imaging, and genetic analyses were acquired at baseline. Disease progression was evaluated in terms of language impairment, global cognitive decline, and functional dependency. RESULTS: During follow-up, one third of subjects presented total language loss, and 20% severe functional dependency. Global cognitive decline after the first year (hazard ratio, 5.93; confidence interval, 1.63-21.56) and high schooling (hazard ratio, 0.07; confidence interval, 0.008-0.74) represented risk factors for functional impairment. The apolipoprotein E status was associated with the progression of cognitive decline. Positive family history for dementia was frequent and 3 genetic autosomal dominant mutations were identified. CONCLUSIONS: There were no differences in the progression of PPA subtypes. Genetics plays an important role in disease onset and progression.

CT assessment of tumor heterogeneity and the potential for the prediction of human papillomavirus status in oropharyngeal squamous cell carcinoma.

The aim of this study is to find a correlation between tumoral heterogeneity of squamous cell carcinoma of the oropharynx and human papillomavirus (HPV) status and to determine whether analysis of texture features of primary lesion on contrast-enhanced CT (CECT) images can be useful in predicting the HPV positivity. Fifty patients with diagnosis of oropharyngeal carcinoma and pre-treatment CECT were included; tumoral heterogeneity of each lesion was evaluated by extracting quantitative texture parameters of first and higher orders. T test and logistic regression were conducted to evaluate the effects of different textural characteristics. There were 35 HPV+ and 15 HPV- lesions. Statistically significant (p < 0.05) differences were seen in multiple higher-order extracted parameters. The logistic regression model correctly classified lesions with an accuracy of 95.2%. CT texture analysis of primary oropharyngeal cancer may be used as a tool for predicting the HPV status.

Biomarkers study in atypical dementia: proof of a diagnostic work-up.

BACKGROUND: An early differentiation between Alzheimer's Disease (AD) and other dementias is crucial for an adequate patients' management, albeit it may result difficult for the occurrence of "atypical presentations." Current diagnostic criteria recognize the importance of biomarkers for AD diagnosis, but still an optimal diagnostic work-up isn't available. OBJECTIVE: Evaluate the utility and reproducibility of biomarkers and propose an "optimal" diagnostic work-up in atypical dementia. METHODS: (1) a retrospective selection of "atypical dementia cases"; (2) a repetition of diagnostic assessment by two neurologists following two different diagnostic work-ups, each consisting of multiple steps; (3) a comparison between diagnostic accuracy and confidence reached at each step by both neurologists and evaluation of the inter-rater agreement. RESULTS: In AD, regardless of the undertaken diagnostic work-up, a significant gain in accuracy was reached by both neurologists after the second step, whereas in frontotemporal dementia (FTD), adding subsequent steps was not always sufficient to increase significantly the baseline accuracy. A relevant increment in diagnostic confidence was detectable after studying pathophysiological markers in AD, and after assessing brain metabolism in FTD. The inter-rater agreement was higher at the second step for the AD group when the pathophysiological markers were available and for the FTD group when the results of FDG-PET were accessible. CONCLUSIONS: In atypical cases of dementia, biomarkers significantly raise diagnostic accuracy, confidence, and agreement. This study introduces a proof of diagnostic work-up that combines imaging and CSF biomarkers and suggests distinct ways to proceed on the basis of a greater diagnostic likelihood.

Segmental quantitative myocardial perfusion with PET for the detection of significant coronary artery disease in patients with stable angina.

PURPOSE: The goal of this study is to determine the technical accuracy of segmental perfusion parameters assessed with quantitative cardiac PET imaging in the evaluation of coronary artery disease (CAD) in patients with stable angina. METHODS: A cohort of patients who participated in the EVINCI protocol underwent an evaluation of coronary anatomy by invasive coronary angiography (ICA) and/or coronary computed tomography angiography (CCTA) and PET myocardial perfusion imaging with H2 (15)O, (13)NH3 or (82)Rb. PET studies were analyzed by two independent observers blinded to clinical and instrumental data, and classified as positive or negative for significant CAD using only segmental perfusion measurements and cut-off values from literature. RESULTS: On a per-patient basis, the overall inter-observer agreement on PET results was 90 % (kappa = 0.79), indicating substantial agreement. On a per-vessel basis, the inter-observer agreement on PET results was 88 % (kappa = 0.74) in the RCA territory, 94 % (kappa = 0.84) in the LAD territory and 94 % (kappa = 0.85) in the LCX territory. Segmental PET measurements correctly identified 85 % of the patients, resulting in a global sensitivity of 86 %, a specificity of 84 %, a positive predictive value (PPV) of 69 % and a negative predictive value (NPV) of 93 %. In vessel-based analyses, quantitative perfusion parameters had a sensitivity, specificity, PPV and NPV of 92 %, 82 %, 42 % and 99 %, respectively, for the detection of significant coronary stenoses in all major coronary arteries. CONCLUSIONS: The assessment of absolute myocardial perfusion parameters measured at a segment level lead to reliable and accurate identification of patients with significant coronary stenosis at ICA and/or CCTA.