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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.

Intrahepatic cholangiocarcinoma (iCCA) is recognized as the second most frequently diagnosed liver malignancy, following closely after hepatocellular carcinoma. Its incidence has seen a global upsurge in the past several years. Unfortunately, due to the lack of well-defined risk factors and limited diagnostic tools, iCCA is often diagnosed at an advanced stage, resulting in a poor prognosis. While surgery is the only potentially curative option, it is rarely feasible. Currently, there are ongoing investigations into various treatment approaches for unresectable iCCA, including conventional chemotherapies, targeted therapies, immunotherapies, and locoregional treatments. This study aims to explore the role of transarterial radioembolization (TARE) in the treatment of unresectable iCCA and provide a comprehensive review. The findings suggest that TARE is a safe and effective treatment option for unresectable iCCA, with a median overall survival (OS) of 14.9 months in the study cohort. Studies on TARE for unresectable iCCA, both as a first-line treatment (as a neo-adjuvant down-staging strategy) and as adjuvant therapy, have reported varying median response rates (ranging from 34% to 86%) and median OS (12-16 mo). These differences can be attributed to the heterogeneity of the patient population and the limited number of participants in the studies. Most studies have identified tumor burden, portal vein involvement, and the patient’s performance status as key prognostic factors. Furthermore, a phase 2 trial evaluated the combination of TARE and chemotherapy (cisplatin-gemcitabine) as a first-line therapy for locally advanced unresectable iCCA. The results showed promising outcomes, including a median OS of 22 mo and a 22% achievement in down-staging the tumor. In conclusion, TARE represents a viable treatment option for unresectable iCCA, and its combination with systemic chemotherapy has shown promising results. However, it is important to consider treatment-independe

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.

Background: The foreseeable clinical availability in Europe of disease-modifying drugs effective in early phases of some neurodegenerative diseases (such as Alzheimer’s disease), shifts the focus to the etiological diagnosis of pre-dementia stages, such as Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD). Current diagnostic approaches employ costly and limited methods such as PET-FDG. Pseudo-continuous Arterial Spin Labeling (pCASL) is emerging as a promising non-invasive alternative, offering rapid, radiation-free brain perfusion measurements through MRI. Recent research demonstrates pCASL's comparable performance to PET-FDG in neurodegenerative dementias, revealing aligned affected brain regions. However, pCASL's suitability for diagnosing MCI and SCD remains unexplored. The CAPE study (NCT05756270) aims to evaluate pCASL's diagnostic potential in MCI and SCD during initial assessments, by correlating cerebral blood flow patterns from pCASL and PET-FDG and comparing their accuracy. Methods: CAPE primary objective will be to compare brain cerebral blood flow and glucose metabolism patterns among MCI and SCD subjects both in general and across ATN classifications of CSF biomarkers. Secondary objectives will encompass evaluating pCASL's potential in distinguishing various subgroups of SCD and MCI, examining correlations between pCASL/PET-FDG and neuropsychological tests, predicting conversion to dementia using pCASL and PET-FDG, and exploring associations between pCASL and diverse fluid biomarkers. The study will recruit up to 150 MCI and SCD subjects, with CDR ≤ 0.5 and age ≤ 80. The research will span 36 months (24-month recruitment phase, and partially overlapping 24-month follow-up). Participants will undergo baseline brain MRI, PET-FDG, neuropsychological tests, lumbar puncture, and blood tests. Neuropsychological tests will be repeated annually twice to evaluate progression to dementia. A customized pipeline for joint quantitative analysis

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 of phonological impairment 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.

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.

Background and purpose: Late-onset (LO) and early-onset (EO) dementia show neurobiological and clinical differences. Clinical and 18fluoro-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.

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. Method: 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). Result: 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.

Background Patients undergoing chemotherapy (CHT) for breast cancer (BC) need a monitoring of cardiac function due to the possible onset of cardiotoxicity. Cardiotoxicity may occur with heart failure but is often asymptomatic and is detectable only by assessing an increase in cardiac volumes (left ventricular end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes) and/or by a reduction of the left ventricular ejection fraction (LV-EF). The primary purpose of this study was to evaluate the role of gated SPECT myocardial perfusion imaging in this setting. Dosimetric evaluation was also assessed. Methods Seventeen BC patients (mean age 55.93 ± 11.04 years)with invasive ductal carcinoma HER2 + treated with surgery and with an anthracycline-based adjuvant CHT, were enrolled. The trend of cardiac function was assessed by evaluation of LV-EF, LV-EDV and LV-ESV using gSPECT in baseline conditions and at 12, 15 and 52 weeks during treatment and then at 6, 12, 24 and 48 months during follow-up. Each patient was studied 15-20 min after injection of 555 MBq of 99mTc-Tetrofosmin with gSPECT (16 frames/cardiac cycle) using an Infinia Hawkeye IV gamma-camera. Dosimetry was assed according to ICRP reports. Results Two out of the 17 patients enrolled left the protocol: one because of a second tumor and the other due to the appearance of cardiotoxicity. 15 patients completed the study: mean LVEF at baseline was 70.67 ± 5.68. The greatest modification occurred after 15th week of treatment, when mean LV-EF showed a significant decrease to 65.67 ± 8.27, while mean LV-EDV and mean LV-ESV increased from 73.60 ± 16.72 up to 84.73 ± 21.11 and from 21.93 ± 7.17 up to 30.27 ± 14.16, respectively. All parameters progressively returned similar to baseline values at the final examination (after 48th month): mean LV-EF 70.20 ± 5.65, LV-EDV 73.40 ± 16.15 and ESV 22.07 ± 7.50. In one case cardiotoxicity occurred at 15th week: LV-EF decreased from 69 to 47%, LV-EDV increased from 92 up to 142 ml a

Background and Objective: Motion due to patient’s breathing can introduce heavy bias in PET/CT, both in image quality and quantitation. This paper is a review of the main technical solutions available to manage movement in PET/CT studies: a) Respiratory Gated (RG), b) Motion Free (MF), c) End Expiration (EE), d) Banana Artefact Management (BAM) and e) Data Driven Gating (DDG). Methods: The most diffused solutions (RG, MF and EE) are based on LIST mode acquisition of a PET Field of View (4D FOV), centered on the anatomical region of interest; to link PET data not only to time and to spatial position but also to the corresponding breathing phase, the synchronized acquisition of the patient’s breathing curve is performed by an external tracking device. Different commercial tools to track and to record patient breathing cycle are available to associate the internal organ motion with a measurable external parameter; for example these systems can measure the pressure on a chest elastic belt, the air flow trough patient nose, the breath-in and breath-out air temperature or the markers movement on the thorax/ abdominal region. Recently DDG techniques are developed to correct respiratory motion without the help of external motion tracking devices and to obtain a comparable result to that based on standard RG protocols. Results: The final result of an RG or DDG protocol is a sequence of 3D images showing organs and lesions movement; using the other motion management options a single 3D motion-free image is obtained without motion artefacts and degradation. Compared to the previously described options the BAM solution is not a real motion management protocol but just a Banana Artefact correction technique obtained using an Attenuation Correction Map calculated merging the Whole Body Helical CT with a Cine CT on the diaphragm area. Conclusion: The motion management in PET/CT imaging shows benefits in terms of image quality, quantification and lesion detectability and it is usef

Background and purpose: Cognitively stimulating life experiences and activities are deemed to moderate the clinical impact of brain damage progressively building a neural and cognitive reserve (CR). CR has been studied extensively in various neurodegenerative disorders, but not in corticobasal degeneration (CBD). Methods: Using Statistical Parametric Mapping 8, years of education, as a determinant of CR, was correlated with tracer uptake on positron emission tomography with 18 F-fluorodeoxyglucose, as a marker of neurodegeneration, in 35 patients with various phenotypes of CBD, including a cognitive–motor composite score or symptoms duration as covariates for controlling disease stage. Results: A cluster of relative hypometabolism was found associated with higher education in the left inferior regions of pre- and post-rolandic gyri and insula, which represent typical loci of neurodegeneration in CBD regardless of clinical presentation. Conclusions: The present findings extend to CBD the evidence gathered in other neurodegenerative disorders that a higher CR has a protective effect against the clinical manifestations of brain degeneration.

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.

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

Purpose: The aim of the present study was to evaluate the added diagnostic value of respiratory-gated 4D18F–FDG PET/CT in liver lesion detection and characterization in a European multicenter retrospective study. Methods: Fifty-six oncological patients (29 males and 27 females, mean age, 61.2 ± 11.2 years) from five European centers, submitted to standard 3D–PET/CT and liver 4D–PET/CT were retrospectively evaluated. Based on visual analysis, liver PET/CT findings were scored as positive, negative, or equivocal both in 3D and 4D PET/CT. The impact of 4D–PET/CT on the confidence in classifying liver lesions was assessed. PET/CT findings were compared to histology and clinical follow-up as standard reference and diagnostic accuracy was calculated for both techniques. At semi-quantitative analysis, SUVmax was calculated for each detected lesion in 3D and 4D–PET/CT. Results: Overall, 72 liver lesions were considered for the analysis. Based on visual analysis in 3D–PET/CT, 32/72 (44.4%) lesions were considered positive, 21/72 (29.2%) negative, and 19/72 (26.4%) equivocal, while in 4D–PET/CT 48/72 (66.7%) lesions were defined positive, 23/72 (31.9%) negative, and 1/72 (1.4%) equivocal. 4D–PET/CT findings increased the confidence in lesion definition in 37/72 lesions (51.4%). Considering 3D equivocal lesions as positive, sensitivity, specificity, and accuracy were 88.9, 70.0, and 83.1%, respectively, while the same figures were 67.7, 90.0, and 73.8% if 3D equivocal findings were included as negative. 4D–PET/CT sensitivity, specificity, and accuracy were 97.8, 90.0, and 95.4%, respectively, considering equivocal lesions as positive and 95.6, 90.0, and 93.8% considering equivocal lesions as negative. The SUVmax of the liver lesions in 4D–PET (mean ± SD, 6.9 ± 3.2) was significantly higher (p < 0.001) than SUVmax in 3D–PET (mean ± SD, 5.2 ± 2.3). Conclusions: Respiratory-gated PET/CT technique is a valuable clinical tool in diagnosing liver lesions, reducing 3D undetermined fi

The aim of the study was to investigate the association between postoperative delirium (POD) and in vivo markers of Alzheimer's disease pathology in nondemented hip fracture surgery patients. POD was assessed with the Confusion Assessment Method. Amyloid load was quantified on 18F-Flutemetamol positron emission tomography images as standardized uptake value ratio. Secondary outcome measures were gray matter volumes, white matter integrity, and functional connectivity at rest. All the patients with POD (POD+, N = 5) were amyloid negative (standardized uptake value ratio <0.59), whereas 6 out of 11 patients without POD (POD−) showed brain amyloid positivity. POD+ compared to POD− displayed: lower gray matter volumes in the amygdala (p = 0.003), in the middle temporal gyrus and in the anterior cingulate cortex (p < 0.001), increased diffusivity in the genu of the corpus callosum and in the anterior corona radiata (p < 0.05), and higher functional connectivity within the default mode network (p < 0.001). POD patients showed altered gray and white matter integrity in the fronto-limbic regions in absence of brain amyloidosis. Based on this preliminary investigation, delirium pathophysiology might be independent of Alzheimer's disease. Future studies on larger samples are needed to confirm this hypothesis.

Objective. The aim of this work was to assess robustness and reliability of an adaptive thresholding algorithm for the biological target volume estimation incorporating reconstruction parameters. Method. In a multicenter study, a phantom with spheres of different diameters (6.5-57.4 mm) was filled with 18F-FDG at different target-to-background ratios (TBR: 2.5-70) and scanned for different acquisition periods (2-5 min). Image reconstruction algorithms were used varying number of iterations and postreconstruction transaxial smoothing. Optimal thresholds (TS) for volume estimation were determined as percentage of the maximum intensity in the cross section area of the spheres. Multiple regression techniques were used to identify relevant predictors of TS. Results. The goodness of the model fit was high (R2: 0.74-0.92). TBR was the most significant predictor of TS. For all scanners, except the Gemini scanners, FWHM was an independent predictor of TS. Significant differences were observed between scanners of different models, but not between different scanners of the same model. The shrinkage on cross validation was small and indicative of excellent reliability of model estimation. Conclusions. Incorporation of postreconstruction filtering FWHM in an adaptive thresholding algorithm for the BTV estimation allows obtaining a robust and reliable method to be applied to a variety of different scanners, without scanner-specific individual calibration.

Although breathing movement can introduce heavy bias in both image quality and quantitation, currently there is lack of interest for the respiratory motion management in PET/CT imaging. The respiratory gating technology has shown significant benefits on image quality, reducing motion related artifacts and increasing quantification. Indeed, many papers have demonstrated that there is a consistent increase of the Standardized Uptake Value (SUV) in gated PET images when compared to ungated ones, particularly for the small lesions located both in liver and in lung. Beside the increase in quantification, respiratory gating can also increase sensitivity, specificity and accuracy of PET/CT. Finally, gated PET/CT can be used for radiation therapy planning, reducing the uncertainty in target definition, optimizing the volume to be treated and reducing the possibility of "missing" during the dose delivery. New technologies, able to define the movement of lesions and organs directly from the PET sinogram, can solve some problems (i.e.: extended acquisition time, radiation exposure) that currently are limiting the clinical use of gated PET/CT. If these new technical improvements for motion compensation will be clinically validated, gated technique could be applied routinely in any PET/CT scan.