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.

Any role for transarterial radioembolization in unresectable intrahepatic cholangiocarcinoma in the era of advanced systemic therapies?

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-independent factors that can influence prognosis. Further research is necessary to identify optimal treatment combinations and predictive factors for a favorable response in iCCA patients.

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.

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.

On the dependence of quantitative diffusion-weighted imaging on scanner system characteristics and acquisition parameters: A large multicenter and multiparametric phantom study with unsupervised clustering analysis.

PURPOSE: The purpose of this multicenter phantom study was to exploit an innovative approach, based on an extensive acquisition protocol and unsupervised clustering analysis, in order to assess any potential bias in apparent diffusion coefficient (ADC) estimation due to different scanner characteristics. Moreover, we aimed at assessing, for the first time, any effect of acquisition plan/phase encoding direction on ADC estimation. METHODS: Water phantom acquisitions were carried out on 39 scanners. DWI acquisitions (b-value = 0-200-400-600-800-1000 s/mm2) with different acquisition plans (axial, coronal, sagittal) and phase encoding directions (anterior/posterior and right/left, for the axial acquisition plan), for 3 orthogonal diffusion weighting gradient directions, were performed. For each acquisition setup, ADC values were measured in-center and off-center (6 different positions), resulting in an entire dataset of 84 × 39 = 3276 ADC values. Spatial uniformity of ADC maps was assessed by means of the percentage difference between off-center and in-center ADC values (Δ). RESULTS: No significant dependence of in-center ADC values on acquisition plan/phase encoding direction was found. Ward unsupervised clustering analysis showed 3 distinct clusters of scanners and an association between Δ-values and manufacturer/model, whereas no association between Δ-values and maximum gradient strength, slew rate or static magnetic field strength was revealed. Several acquisition setups showed significant differences among groups, indicating the introduction of different biases in ADC estimation. CONCLUSIONS: Unsupervised clustering analysis of DWI data, obtained from several scanners using an extensive acquisition protocol, allows to reveal an association between measured ADC values and manufacturer/model of scanner, as well as to identify suboptimal DWI acquisition setups for accurate ADC estimation.

The impact of time-of-flight, resolution recovery, and noise modelling in reconstruction algorithms in non-solid-state detectors PET/CT scanners: - multi-centric comparison of activity recovery in a 68Ge phantom.

The reconstruction algorithms implemented on PET/CT scanners offer gain in activity recovery of small lesions at an extent that is not full known yet. METHODS: A cylindrical phantom with warm background and hot spheres filled with a 68Ge epoxy was acquired with four non-state-solid-detectors PET/CT scanners: mCT, Ingenuity TF, Discovery 710, and IQ. Images were reconstructed switching on and off time-of-flight (TOF), point spread function (PSF) modelling, and Bayesian penalised likelihood (BPL). Images were reconstructed with the default parameters recommended by the manufacturers. The recovery coefficient (RCmax), defined as the ratio of the measured maximum activity concentration in each sphere and the actual one, and the coefficient of variation (CoVBAC) defined as the ratio of the standard deviation and the average of background activity concentration were measured. RESULTS: While with IR alone, complete recovery of the activity concentration is achieved down to the 22 mm diameter's sphere, with TOF, TOF + PSF and BPL it is achieved down to the 17 mm diameter one. At smaller dimensions, the difference among the various studied reconstruction algorithms is substantial for the 13- and 17-mm diameters' spheres for all scanners and for all reconstructions with a considerable gain in RCmax when PSF and BPL are used. At 10 mm diameter's sphere the difference among the algorithms is significantly reduced, except for BPL which still guarantees a gain in RCmax.

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.

Evaluation of PET quantitation accuracy among multiple discovery IQ PET/CT systems via NEMA image quality test.

INTRODUCTION: Quantitative imaging biomarkers are becoming usual in oncology for assessing therapy response. The harmonization of image quantitation reporting has become of utmost importance due to the multi-center trials increase. The NEMA image quality test is often considered for the evaluation of quantitation and is more accurate with a radioactive solid phantom that reduces variability. The goal of this project is to determine the level of variability among imaging centers if acquisition and imaging protocol parameters are left to the center's preference while all other parameters are fixed including the scanner type. METHODS: A NEMA-IQ phantom filled with radioactive 68Ge solid resin was imaged in five clinical sites throughout Europe. Sites reconstructed data with OSEM and BSREM algorithms applying the sites' clinical parameters. Images were analyzed according with the NEMA-NU2-2012 standard using the manufacturer-provided NEMA tools to calculate contrast recovery (CR) and background variability (BV) for each sphere and the lung error (LE) estimation. In addition, a 18F-filled NEMA-IQ phantom was also evaluated to obtain a gauge for variability among centers when the sites were provided with identical specific instructions for acquisition and reconstruction protocol (the aggregate of data from 12 additional sites is presented). RESULTS: The data using the 68Ge solid phantom showed no statistical differences among different sites, proving a very good reproducibility among the PET center models even if dispersion of data is higher with OSEM compared to BSREM. Furthermore, BSREM shows better CR and comparable BV, while LE is slightly reduced. Two centers exhibit significant differences in CR and BV values for the 18F NEMA NU2-2012 experiments; these outlier results are explained. CONCLUSION: The same PET system type from the various sites produced similar quantitative results, despite allowing each site to choose their clinical protocols with no restriction on data acquisition and reconstruction parameters. BSREM leads to lower dispersion of quantitative data among different sites. A solid radioactive phantom may be recommended to qualify the sites to perform quantitative imaging.

Model observers for Low Contrast Detectability evaluation in dynamic angiography: A feasible approach.

PURPOSE: To evaluate the feasibility of spatio-temporal generalisation of mathematical methods for protocol optimisation in interventional radiology. MATERIALS AND METHODS: Two model observers were considered:Furthermore, Low Contrast Detectability (LCD) was evaluated with a generalised statistical method by taking into account the noise integration capability of the human eye. A series of two alternative force choices (2AFC) experiments performed by four observers were used to evaluate the reliability of the proposed models. The evaluation of the mathematical methods was performed by comparing their results to the human observer performances in two steps: 1. Firstly, a series of simulated images were used to tune the models 2. In the second phase, tuned models were applied both to simulated images and actual images obtained with a commercial phantom to evaluate detectability scores. RESULTS: Evaluation with simulated images shows a good agreement with 2AFC results (RMSE < 10%). Phantom-based evaluations show a general decrease of such agreement, characterized by an RMSE lower than 16%. CONCLUSIONS: The agreement with human observer experiments supports the feasibility of the proposed generalisations. Thus, they could be introduced in quality control programmes for a deeper protocol-characterisation or for clinical protocol-optimization when dynamic images are involved.

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.

A straightforward multiparametric quality control protocol for proton magnetic resonance spectroscopy: Validation and comparison of various 1.5 T and 3 T clinical scanner systems.

PURPOSE: The aim of this study was to propose and validate across various clinical scanner systems a straightforward multiparametric quality assurance procedure for proton magnetic resonance spectroscopy (MRS). METHODS: Eighteen clinical 1.5 T and 3 T scanner systems for MRS, from 16 centres and 3 different manufacturers, were enrolled in the study. A standard spherical water phantom was employed by all centres. The acquisition protocol included 3 sets of single (isotropic) voxel (size 20 mm) PRESS acquisitions with unsuppressed water signal and acquisition voxel position at isocenter as well as off-center, repeated 4/5 times within approximately 2 months. Water peak linewidth (LW) and area under the water peak (AP) were estimated. RESULTS: LW values [mean (standard deviation)] were 1.4 (1.0) Hz and 0.8 (0.3) Hz for 3 T and 1.5 T scanners, respectively. The mean (standard deviation) (across all scanners) coefficient of variation of LW and AP for different spatial positions of acquisition voxel were 43% (20%) and 11% (11%), respectively. The mean (standard deviation) phantom T2values were 1145 (50) ms and 1010 (95) ms for 1.5 T and 3 T scanners, respectively. The mean (standard deviation) (across all scanners) coefficients of variation for repeated measurements of LW, AP and T2 were 25% (20%), 10% (14%) and 5% (2%), respectively. CONCLUSIONS: We proposed a straightforward multiparametric and not time consuming quality control protocol for MRS, which can be included in routine and periodic quality assurance procedures. The protocol has been validated and proven to be feasible in a multicentre comparison study of a fairly large number of clinical 1.5 T and 3 T scanner systems.

Dependence of apparent diffusion coefficient measurement on diffusion gradient direction and spatial position - A quality assurance intercomparison study of forty-four scanners for quantitative diffusion-weighted imaging.

PURPOSE: To propose an MRI quality assurance procedure that can be used for routine controls and multi-centre comparison of different MR-scanners for quantitative diffusion-weighted imaging (DWI). MATERIALS AND METHODS: 44 MR-scanners with different field strengths (1 T, 1.5 T and 3 T) were included in the study. DWI acquisitions (b-value range 0-1000 s/mm2), with three different orthogonal diffusion gradient directions, were performed for each MR-scanner. All DWI acquisitions were performed by using a standard spherical plastic doped water phantom. Phantom solution ADC value and its dependence with temperature was measured using a DOSY sequence on a 600 MHz NMR spectrometer. Apparent diffusion coefficient (ADC) along each diffusion gradient direction and mean ADC were estimated, both at magnet isocentre and in six different position 50 mm away from isocentre, along positive and negative AP, RL and HF directions. RESULTS: A good agreement was found between the nominal and measured mean ADC at isocentre: more than 90% of mean ADC measurements were within 5% from the nominal value, and the highest deviation was 11.3%. Away from isocentre, the effect of the diffusion gradient direction on ADC estimation was larger than 5% in 47% of included scanners and a spatial non uniformity larger than 5% was reported in 13% of centres. CONCLUSION: ADC accuracy and spatial uniformity can vary appreciably depending on MR scanner model, sequence implementation (i.e. gradient diffusion direction) and hardware characteristics. The DWI quality assurance protocol proposed in this study can be employed in order to assess the accuracy and spatial uniformity of estimated ADC values, in single- as well as multi-centre studies.

Motion Management in PET/CT: Technological Solutions.

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 useful both in diagnostic and radiotherapy planning.

Added diagnostic value of respiratory-gated 4D 18F-FDG PET/CT in the detection of liver lesions: a multicenter study.

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 findings, improving diagnostic accuracy, and confidence in reporting. 4D-PET/CT also improved the quantification of SUVmax of liver lesions.

Association of postoperative delirium with markers of neurodegeneration and brain amyloidosis: a pilot study.

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.

Respiratory Motion Management in PET/CT: Applications and Clinical Usefulness.

BACKGROUND AND OBJECTIVE: Breathing movement can introduce heavy bias in both image quality and quantitation in PET/CT. The aim of this paper is a review of the literature to evaluate the benefit of respiratory gating in terms of image quality, quantification and lesion detectability. METHODS: A review of the literature published in the last 10 years and dealing with gated PET/CT technique has been performed, focusing on improvement in quantification, lesion detectability and diagnostic accuracy in neoplastic lesion. In addition, the improvement in the definition of radiotherapy planning has been evaluated. RESULTS: There is a consistent increase of the Standardized Uptake Value (SUV) in gated PET images when compared to ungated ones, particularly for lesions located in liver and in lung. Respiratory gating can also increase sensitivity, specificity and accuracy of PET/CT. 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. Moreover, new technologies, able to define the movement of lesions and organs directly from the PET sinogram, can solve some problems that currently are limiting the clinical use of gated PET/CT (i.e.: extended acquisition time, radiation exposure). CONCLUSION: The published literature demonstrated that respiratory gating PET/CT is a valid technique to improve quantification, lesion detectability of lung and liver tumors and can better define the radiotherapy planning of moving lesions and organs. If new technical improvements for motion compensation will be clinically validated, gated technique could be applied routinely in any PET/CT scan.