Artificial intelligence of imaging and clinical neurological data for predictive, preventive and personalized (P3) medicine for Parkinson Disease: The NeuroArtP3 protocol for a multi-center research study.

BACKGROUND: The burden of Parkinson Disease (PD) represents a key public health issue and it is essential to develop innovative and cost-effective approaches to promote sustainable diagnostic and therapeutic interventions. In this perspective the adoption of a P3 (predictive, preventive and personalized) medicine approach seems to be pivotal. The NeuroArtP3 (NET-2018-12366666) is a four-year multi-site project co-funded by the Italian Ministry of Health, bringing together clinical and computational centers operating in the field of neurology, including PD. OBJECTIVE: The core objectives of the project are: i) to harmonize the collection of data across the participating centers, ii) to structure standardized disease-specific datasets and iii) to advance knowledge on disease's trajectories through machine learning analysis. METHODS: The 4-years study combines two consecutive research components: i) a multi-center retrospective observational phase; ii) a multi-center prospective observational phase. The retrospective phase aims at collecting data of the patients admitted at the participating clinical centers. Whereas the prospective phase aims at collecting the same variables of the retrospective study in newly diagnosed patients who will be enrolled at the same centers. RESULTS: The participating clinical centers are the Provincial Health Services (APSS) of Trento (Italy) as the center responsible for the PD study and the IRCCS San Martino Hospital of Genoa (Italy) as the promoter center of the NeuroartP3 project. The computational centers responsible for data analysis are the Bruno Kessler Foundation of Trento (Italy) with TrentinoSalute4.0 -Competence Center for Digital Health of the Province of Trento (Italy) and the LISCOMPlab University of Genoa (Italy). CONCLUSIONS: The work behind this observational study protocol shows how it is possible and viable to systematize data collection procedures in order to feed research and to advance the implementation of a P3 approach into the clinical practice through the use of AI models.

Spontaneous unilateral spatial neglect recovery after brain tumour resection: A multimodal diffusion and rs-fMRI case report.

Patients with unilateral spatial neglect (USN) are unable to explore or to report stimuli presented in the left personal and extra-personal space. USN is usually caused by lesion of the right parietal lobe: nowadays, it is also clear the key role of structural connections (the second and the third branch of the right Superior Longitudinal Fasciculus, respectively, SLF II and III) and functional networks (Dorsal and Ventral Attention Network, respectively, DAN and VAN) in USN. In this multimodal case report, we have merged those structural and functional information derived from a patient with a right parietal lobe tumour and USN before surgery. Functional, structural and neuropsychological data were also collected 6 months after surgery, when the USN was spontaneously recovered. Diffusion metrics and Functional Connectivity (FC) of the right SLF and DAN, before and after surgery, were compared with the same data of a patient with a tumour in a similar location, but without USN, and with a control sample. Results indicate an impairment in the right SLF III and a reduction of FC of the right DAN in patients with USN before surgery compared to controls; after surgery, when USN was recovered, patient's diffusion metrics and FC showed no differences compared to the controls. This single case and its multimodal approach reinforce the crucial role of the right SLF III and DAN in the development and recovery of egocentric and allocentric extra-personal USN, highlighting the need to preserve these structural and functional areas during brain surgery.

Non-lesional white matter in relapsing-remitting multiple sclerosis assessed by multicomponent T2 relaxation.

INTRODUCTION: The purpose of the study is to investigate, by T2 relaxation, non-lesional white matter (WM) in relapsing-remitting (RR) multiple sclerosis (MS). METHODS: Twenty stable RR MS patients underwent 1.5T Magnetic Resonance Imaging (MRI) with 3D Fluid-Attenuated Inversion-Recovery (FLAIR), 3D-T1-weighted, and T2-relaxation multi-echo sequences. The Lesion Segmentation Tool processed FLAIR images to identify focal lesions (FLs), whereas T1 images were segmented to identify WM and FL sub-volumes with T1 hypo-intensity. Non-lesional WM was obtained as the segmented WM, excluding FL volumes. The multi-echo sequence allowed decomposition into myelin water, intra-extracellular water, and free water (Fw), which were evaluated on the segmented non-lesional WM. Correlation analysis was performed between the non-lesional WM relaxation parameters and Expanded Disability Status Scale (EDSS), disease duration, patient age, and T1 hypo-intense FL volumes. RESULTS: The T1 hypo-intense FL volumes correlated with EDSS. On the non-lesional WM, the median Fw correlated with EDSS, disease duration, age, and T1 hypo-intense FL volumes. Bivariate EDSS correlation of FL volumes and WM T2-relaxation parameters did not improve significance. CONCLUSION: T2 relaxation allowed identifying subtle WM alterations, which significantly correlated with EDSS, disease duration, and age but do not seem to be EDSS-predictors independent from FL sub-volumes in stable RR patients. Particularly, the increase in the Fw component is suggestive of an uninvestigated prodromal phenomenon in brain degeneration.

Combination of transjugular intrahepatic portosystemic shunt and antegrade through-the-TIPS coil embolization for bleeding mixed-type ectopic ileal varices.

A 61-year-old man with alcoholic cirrhosis and a history of severe cholecystitis leading to secondary thrombosis of the recanalized paraumbilical vein was admitted to our hospital for recurrent gastrointestinal bleeding and severe anemia. Capsule endoscopy and CT angiography detected profuse bleeding in the proximal ileum from ectopic ileal varices. Hepatic venous-portal gradient (HVPG) measurement was consistent with severe portal hypertension. Persistent bleeding despite transjugular intrahepatic portosystemic shunt (TIPS) placement required a combined approach with antegrade through-the-TIPS coil embolization of the ileal varices.

The role of cardiac imaging before and after left atrial appendage standalone thoracoscopic exclusion.

AIMS: To assess the characteristics of left atrial appendage (LAA) stump and left atrial (LA) volume after standalone totally thoracoscopic LAA exclusion in 40 patients with nonvalvular atrial fibrillation (NVAF) and contraindications to oral anticoagulation (OAC), using cardiac computed tomography (CCT) and transoesophageal echocardiography (TOE). METHODS: Using CCT and TOE, we evaluated correct AtriClip Pro II positioning, the presence and characteristics of the LAA stump and the postprocedural LA volume, at 3 months' follow-up. Stump depth was measured with both CCT and TOE using a new method, based on left circumflex artery (LCX) course. RESULTS: After placement of AtriClip, all 40 patients discontinued OAC, and no stroke occurred. LAA exclusion was achieved in 40/40 patients at 3 months' follow-up. LAA stump (depth <10 mm in 12/18 stump, 67%) was observed in 18 patients. The overall (LA + LAA) volume and isolated LA volume were statistically different when comparing cases with and without LAA stump (P < 0.02). LAA ostium dimensions (perimeter and area) and LAA volume correlate with stump depth (P < 0.02). There was a high correlation between CCT and TOE in stump identification and depth measurement (P < 0.02). Compared with the baseline, CCT LA volume increased (P < 0.01) at 3 months' follow-up. CONCLUSION: Preprocedural and postprocedural CCT and TOE are useful and comparable in patients undergoing standalone totally thoracoscopic exclusion of LAA, because these imaging methods can identify anatomical LAA and LA characteristics predisposing for a postprocedural residual stump.

A Novel Nomogram Based on Initial Features to Predict BPH Progression.

Objectives: The aim of this study was to establish a tool to identify patients at risk for pharmaceutical and surgical interventions for benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS) over a 10 year follow-up. Methods: The data of patients with mild to moderate male LUTS undergoing phytotherapy from January to December 2010 were reviewed. Patients were followed for 10 years through medical visits and telephone consultations. The outcomes were (1) treatment switch from phytotherapy or no therapy to alpha-blockers or 5α-reductase inhibitors (5-ARI), and (2) clinical progression (acute urinary retention or need for surgery). Two calibrated nomograms (one for each outcome) were constructed on significant predictors at multivariate analysis. Results: A total of 107 patients with a median age of 55 years at presentation were included; 47% stopped or continued phytotherapy, while 53% switched to alpha-blockers and/or 5-ARI after a median time of 24 months. One-third in the second group experienced clinical progression after a median time of 54 months. Age, symptom score, peak flow rate (Qmax), prostate-specific antigen (PSA), and post-void residual volume were significantly associated with the outcomes. According to our nomograms, patients switching therapy or progressing clinically had average scores of 75% and 40% in the dedicated nomograms, respectively, as compared to 25% and <5% in patients who did not reach any outcome. Conclusions: We developed a nomogram to predict the risk of pharmaceutical or surgical interventions for BPH-related LUTS at 10 years from presentation. On the basis of our models, thresholds of >75% and >40% for high risk and <25% and <5% for low risk of pharmaceutical or surgical interventions, respectively, can be proposed.

Segregated circuits for phonemic and semantic fluency: A novel patient-tailored disconnection study.

Phonemic and semantic fluency are neuropsychological tests widely used to assess patients' language and executive abilities and are highly sensitive tests in detecting language deficits in glioma patients. However, the networks that are involved in these tasks could be distinct and suggesting either a frontal (phonemic) or temporal (semantic) involvement. 42 right-handed patients (26 male, mean age = 52.5 years, SD=±13.3) were included in this retrospective study. Patients underwent awake (54.8%) or asleep (45.2%) surgery for low-grade (16.7%) or high-grade-glioma (83.3%) in the frontal (64.3%) or temporal lobe (35.7%) of the left (50%) or right (50%) hemisphere. Pre-operative tractography was reconstructed for each patient, with segmentation of the inferior fronto-occipital fasciculus (IFOF), arcuate fasciculus (AF), uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), third branch of the superior longitudinal fasciculus (SLF-III), frontal aslant tract (FAT), and cortico-spinal tract (CST). Post-operative percentage of damage and disconnection of each tract, based on the patients' surgical cavities, were correlated with verbal fluencies scores at one week and one month after surgery. Analyses of differences between fluency scores at these timepoints (before surgery, one week and one month after surgery) were performed; lesion-symptom mapping was used to identify the correlation between cortical areas and post-operative scores. Immediately after surgery, a transient impairment of verbal fluency was observed, that improved within a month. Left hemisphere lesions were related to a worse verbal fluency performance, being a damage to the left superior frontal or temporal gyri associated with phonemic or semantic fluency deficit, respectively. At a subcortical level, disconnection analyses revealed that fluency scores were associated to the involvement of the left FAT and the left frontal part of the IFOF for phonemic fluency, and the association was still present one month after surgery. For semantic fluency, the correlation between post-surgery performance emerged for the left AF, UF, ILF and the temporal part of the IFOF, but disappeared at the follow-up. This approach based on the patients' pre-operative tractography, allowed to trace for the first time a dissociation between white matter pathways integrity and verbal fluency after surgery for glioma resection. Our results confirm the involvement of a frontal anterior pathway for phonemic fluency and a ventral temporal pathway for semantic fluency. Finally, our longitudinal results suggest that the frontal executive pathway requires a longer interval to recover compared to the semantic one.

The role of the default mode network in longitudinal functional brain reorganization of brain gliomas.

The study of patients after glioma resection offers a unique opportunity to investigate brain reorganization. It is currently unknown how the whole-brain connectomic profile evolves longitudinally after surgical resection of a glioma and how this may be associated with tumor characteristics and cognitive outcome. In this longitudinal study, we investigate the impact of tumor lateralization and grade on functional connectivity (FC) in highly connected networks, or hubs, and cognitive performance. Twenty-eight patients (17 high-grade, 11 low-grade gliomas) underwent longitudinal pre/post-surgery resting-state fMRI scans and neuropsychological assessments (73 total measures). FC matrices were constructed considering as functional hubs the default mode (DMN) and fronto-parietal networks. No-hubs included primary sensory functional networks and any other no-hubs nodes. Both tumor hemisphere and grade affected brain reorganization post-resection. In right-hemisphere tumor patients, regardless of grade and relative to left-hemisphere gliomas, FC increased longitudinally after the intervention, both in terms of FC within hubs (phubs = 0.0004) and FC between hubs and no-hubs (phubs-no-hubs = 0.005). Regardless of tumor side, only lower-grade gliomas showed longitudinal FC increases relative to high-grade tumors within a precise hub network, the DMN. The neurocognitive profile was longitudinally associated with spatial features of the connectome, mainly within the DMN. We provide evidence that clinical glioma features, such as lateralization and grade, affect post-surgical longitudinal functional reorganization and cognitive recovery. The data suggest a possible role of the DMN in supporting cognition, providing useful information for prognostic prediction and surgical planning.

Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives.

Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have always been considered rare tumors, their incidence has risen over the past few decades. They represent a highly heterogeneous group of neoplasms with several prognostic factors, including disease stage, proliferative index (Ki67), and tumor differentiation. Most of these neoplasms express somatostatin receptors on the cell surface, a feature that has important implications in terms of prognosis, diagnosis, and therapy. Although International Guidelines propose algorithms aimed at guiding therapeutic strategies, GEP-NEN patients are still very different from one another, and the need for personalized treatment continues to increase. Radical surgery is always the best option when feasible; however, up to 80% of cases are metastatic upon diagnosis. Regarding medical treatments, as GEP-NENs are characterized by relatively long overall survival, multiple therapy lines are adopted during the lifetime of these patients, but the optimum sequence to be followed has never been clearly defined. Furthermore, although new molecular markers aimed at predicting the response to therapy, as well as prognostic scores, are currently being studied, their application is still far from being part of daily clinical practice. As they represent a complex disease, with therapeutic protocols that are not completely standardized, GEP-NENs require a multidisciplinary approach. This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.

Quantitative Multicomponent T2 Relaxation Showed Greater Sensitivity Than Flair Imaging to Detect Subtle Alterations at the Periphery of Lower Grade Gliomas.

PURPOSE: To demonstrate that quantitative multicomponent T2 relaxation can be more sensitive than conventional FLAIR imaging for detecting cerebral tissue abnormalities. METHODS: Six patients affected by lower-grade non-enhancing gliomas underwent T2 relaxation and FLAIR imaging before a radiation treatment by proton therapy (PT) and were examined at follow-up. The T2 decay signal obtained by a thirty-two-echo sequence was decomposed into three main components, attributing to each component a different T2 range: water trapped in the lipid bilayer membrane of myelin, intra/extracellular water and cerebrospinal fluid. The T2 quantitative map of the intra/extracellular water was compared with FLAIR images. RESULTS: Before PT, in five patients a mismatch was observed between the intra/extracellular water T2 map and FLAIR images, with peri-tumoral areas of high T2 that typically extended outside the area of abnormal FLAIR hyper-intensity. Such mismatch regions evolved into two different types of patterns. The first type, observed in three patients, was a reduced extension of the abnormal regions on T2 map with respect to FLAIR images (T2 decrease pattern). The second type, observed in two patients, was the appearance of new areas of abnormal hyper-intensity on FLAIR images matching the anomalous T2 map extension (FLAIR increase pattern), that was considered as asymptomatic radiation induced damage. CONCLUSION: Our preliminarily results suggest that quantitative T2 mapping of the intra/extracellular water component was more sensitive than conventional FLAIR imaging to subtle cerebral tissue abnormalities, deserving to be further investigated in future clinical studies.

Clinical results of active scanning proton therapy for primary liver tumors.

BACKGROUND: Evidence for the efficacy of radiation therapy for primary liver cancer is growing. In this context, proton therapy (PT) can potentially improve the therapeutic ratio, as demonstrated by recent clinical studies. Here we report the first European clinical experience on the use of PT for primary liver cancer. METHODS: All patients treated for primary liver cancer in our center entered the analysis. Patients were simulated during deep expiration breath-hold. A 15-fraction treatment schedule was adopted using active scanning PT. Clinical outcome and toxicity were retrospectively analyzed. RESULTS: Between January 2018 and December 2019, 18 patients were treated. Fourteen patients had hepatocellular carcinoma (HCC), three patients had intrahepatic cholangiocarcinoma (ICC), and one patient had synchronous ICC-HCC. The Child-Pugh score was A5 in the majority of patients with HCC (71.4%). Median prescription dose was 58.05 Gy (range, 50.31-67.5). Median follow-up was 10 months (range, 1-19). The majority of deaths occurred from liver tumor progression. One-year overall survival (OS) was 63%. A significant correlation between worse OS and patient performance status, vascular invasion, and tumor stage was recorded. One-year local control was 90%. Toxicity was low, with a decrease in Child-Pugh score ⩾2 points detected in one patient. No cases of classic radiation-induced liver disease occurred. CONCLUSIONS: Our initial results of active scanning PT for primary liver cancer demonstrated the feasibility, safety, and effectiveness of this advanced technique in this setting. The potential of the combination of PT with other locoregional therapies is under evaluation.

Planning Brain Tumor Resection Using a Probabilistic Atlas of Cortical and Subcortical Structures Critical for Functional Processing: A Proof of Concept.

BACKGROUND: Functional preoperative planning for resection of intrinsic brain tumors in eloquent areas is still a challenge. Predicting subcortical functional framework is especially difficult. Direct electrical stimulation (DES) is the recommended technique for resection of these lesions. A reliable probabilistic atlas of the critical cortical epicenters and subcortical framework based on DES data was recently published. OBJECTIVE: To propose a pipeline for the automated alignment of the corticosubcortical maps of this atlas with T1-weighted MRI. METHODS: To test the alignment, we selected 10 patients who underwent resection of brain lesions by using DES. We aligned different cortical and subcortical functional maps to preoperative volumetric T1 MRIs (with/without gadolinium). For each patient we quantified the quality of the alignment, and we calculated the match between the location of the functional sites found at DES and the functional maps of the atlas. RESULTS: We found an accurate brain extraction and alignment of the functional maps with both the T1 MRIs of each patient. The matching analysis between functional maps and functional responses collected during surgeries was 88% at cortical and, importantly, 100% at subcortical level, providing a further proof of the correct alignment. CONCLUSION: We demonstrated quantitatively and qualitatively the reliability of this tool that may be used for presurgical planning, providing further functional information at the cortical level and a unique probabilistic prevision of distribution of the critical subcortical structures. Finally, this tool offers the chance for multimodal planning through integrating this functional information with other neuroradiological and neurophysiological techniques.

Cardiac-CT and cardiac-MR cost-effectiveness: a literature review.

Cardiovascular diseases are still among the first causes of death worldwide with a huge impact on healthcare systems. Within these conditions, the correct diagnosis of coronary artery disease with the most appropriate imaging-based evaluations is of utmost importance. The sustainability of the healthcare systems, considering the high economic burden of modern cardiac imaging equipments, makes cost-effective analysis an important tool, currently used for weighing different costs and health outcomes, when policy makers have to allocate funds and to prioritize interventions, getting the most out of their financial resources. This review aims at evaluating cost-effective analysis in the more recent literature, focused on the role of Calcium Score, coronary computed tomography angiography and cardiac magnetic resonance.

Unusual diagnostic findings in temporal lobe epilepsy: A combined MRI and 18F-dopa case study.

Temporal lobe epilepsy is the most common focal epilepsy in adults and often causes pharmacoresistant seizures. Magnetic resonance imaging (MRI) and PET studies have widely demonstrated a number of morphological and molecular abnormalities in epilepsy. However, considering the dopaminergic system, only a bilateral 18F-DOPA uptake reduction within the basal ganglia has been described. We report the unusual finding of increased 18F-DOPA uptake in a patient with focal recurrent seizures and "deja vu" experiences in the setting of cortical swelling detected at MRI exam. The final diagnosis was in in keeping with hippocampal sclerosis, confirmed during follow-up MR exams. In this case 18F-DOPA uptake may represent increased dopamine transport induced by seizures. Nuclear medicine physicians and radiologists should be aware of clinical and electroencephalographic findings when interpreting brain areas of tracer uptake, which are not always related to malignancy.

Effects of supra-total resection in neurocognitive and oncological outcome of high-grade gliomas comparing asleep and awake surgery.

PURPOSE: Awake surgery is an established technique for resection of low-grade gliomas, while its possible benefit for resection of high-grade gliomas (HGGs) needs further confirmations. This retrospective study aims to compare overall survival, extent of resection (EOR) and cognitive outcome in two groups of HGGs patients submitted to asleep or awake surgery. METHODS: Thirty-three patients submitted to Gross Total Resection of contrast-enhancing area of HGGs were divided in two homogeneous groups: awake (AWg; N = 16) and asleep surgery (ASg; N = 17). All patients underwent to an extensive neuropsychological assessment before surgery (time_1), 1-week (time_2) and 4-months (time_3) after surgery. We performed analyses to assess differences in cognitive performances between groups, cognitive outcomes in each group and EOR. A comparison of overall survival (OS) between the two groups was conducted. RESULTS: Statistical analyses showed no differences between groups at time_2 and time_3 in each cognitive domain, excluding selective attention that resulted higher in the AWg before surgery. Regarding cognitive outcomes, we found a reversible worsening of memory and constructional praxis, and a significant recovery at time_3, similar for both groups. Assessment of time_3 in respect to time_1 never showed differences (all ps > .074). Moreover we found a significant lower level of tumor infiltration after surgery for AWg (p < .05), with an influence on OS (p < .05). Indeed, patients of AWg showed a significant longer OS in comparison to those in the ASg (p < .01). This result was confirmed even considering only wildtype Glioblastoma (p < .05). CONCLUSION: These results indicate that awake surgery, and in general a supra-total resection of enhancing area, can improve OS in HGGs patients, preserving neuro-cognitive profile and quality of life.