P. Scifo - Academia.edu (original) (raw)

Papers by P. Scifo

European Journal of Nuclear Medicine and Molecular Imaging

To explore the role of fully hybrid 68Ga-DOTATOC PET/MR imaging and radiomic parameters in predic... more To explore the role of fully hybrid 68Ga-DOTATOC PET/MR imaging and radiomic parameters in predicting histopathological prognostic factors in patients with pancreatic neuroendocrine tumours (PanNETs) undergoing surgery. One hundred eighty-seven consecutive 68Ga-DOTATOC PET/MRI scans (March 2018–June 2020) performed for gastroenteropancreatic neuroendocrine tumour were retrospectively evaluated; 16/187 patients met the eligibility criteria (68Ga-DOTATOC PET/MRI for preoperative staging of PanNET and availability of histological data). PET/MR scans were qualitatively and quantitatively interpreted, and the following imaging parameters were derived: PET-derived SUVmax, SUVmean, somatostatin receptor density (SRD), total lesion somatostatin receptor density (TLSRD), and MRI-derived apparent diffusion coefficient (ADC), arterial and late enhancement, necrosis, cystic degeneration, and maximum diameter. Additionally, first-, second-, and higher-order radiomic parameters were extracted from both PET and MRI scans. Correlations with several PanNETs’ histopathological prognostic factors were evaluated using Spearman’s coefficient, while the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate parameters’ predictive performance. Primary tumour was detected in all 16 patients (15/16 by 68Ga-DOTATOC PET and 16/16 by MRI). SUVmax and SUVmean resulted good predictors of lymphnodal (LN) involvement (AUC of 0.850 and 0.783, respectively). Second-order radiomic parameters GrayLevelVariance and HighGrayLevelZoneEmphasis extracted from T2 MRI demonstrated significant correlations with LN involvement (adjusted p = 0.009), also showing good predictive performance (AUC = 0.992). This study demonstrates the role of the fully hybrid PET/MRI tool for the synergic function of imaging parameters extracted by the two modalities and highlights the potentiality of imaging and radiomic parameters in assessing histopathological features of PanNET aggressiveness.

Journal of Clinical Oncology, 2007

3540 Background: NGRhTNF is a vascular targeting agent (VTA) exploiting a tumour homing peptide (... more 3540 Background: NGRhTNF is a vascular targeting agent (VTA) exploiting a tumour homing peptide (CNGRCG) selectively binding angiogenic vessels in solid tumours where NGRhTNF specific binding relies on dynamic interactions with TNF-receptors and aminopeptidase N (CD13). NGRhTNF combines activity on tumour vascular permeability and direct anticancer activity. Consistently, mouse preclinical data indicate significant synergy between low dose NGRhTNF and cytotoxic agents. Methods: 4 dose levels of NGRhTNF (0.2 up to 1.6 mcg/sqm) have been administered q 3 w in 16 patients. Main end-points included safety, anticancer activity and pharmacokinetic.Measurement of circulating tumor and endothelial cells (CTC and CEC), sTNFRI and s TNFRII, along with plasma cyto-chemokine profile have been performed. Results: 16 patients were enrolled (6F/10M);median age 60,range 43–73). Toxicity was limited to constitutional symptoms, and chills were the most frequent event (40%). Over a median follow-up of...

American Journal of Physiology-Endocrinology and Metabolism, 2002

Antiretroviral therapy in human immunodeficiency virus (HIV)-positive patients can induce a lipod... more Antiretroviral therapy in human immunodeficiency virus (HIV)-positive patients can induce a lipodystrophy syndrome of peripheral fat wasting and central adiposity, dyslipidemia, and insulin resistance. To test whether in this syndrome insulin resistance is associated with abnormal muscle handling of fatty acids, 12 HIV-1 patients (8 females/4 males , age = 26 ± 2 yr, HIV duratio n = 8 ± 1 yr, body mass index = 22.0 ± 1.0 kg/m2, on protease inhibitors and nucleoside analog RT inhibitors) and 12 healthy subjects were studied. HIV-1 patients had a total body fat content (assessed by dual-energy X-ray absorptiometry) similar to that of controls (22 ± 1 vs. 23 ± 2%; P = 0.56), with a topographic fat redistribution characterized by reduced fat content in the legs (18 ± 2 vs. 32 ± 3%; P < 0.01) and increased fat content in the trunk (25 ± 2 vs. 19 ± 2%; P = 0.03). In HIV-positive patients, insulin sensitivity (assessed by QUICKI) was markedly impaired (0.341 ± 0.011 vs. 0.376 ± 0.007; P...

Introduction:. Standard spherical deconvolution approaches assume that HARDI signal can be modele... more Introduction:. Standard spherical deconvolution approaches assume that HARDI signal can be modeled as a convolution between a common fiber response and a fiber orientation distribution function [1][2]. Recent spherical deconvolution methods improved the quality of the results introducing the non negative constraint of the solution [3][4][5]. It can be verified, however, that instability problems, such as spurious fiber orientations, could be related not only to noise robustness but also to signal contributes, such as from isotropic tissues, that are not properly taken into account. To develop new and more advanced fiber tracking techniques it is essential that fiber orientations are meaningful not only in main white matter (WM) fascicles but also in regions where partial volume effect between WM and isotropic tissue occurs. In this work, we proposed a modified damped version of the Richardson Lucy (RL) spherical deconvolution approach to reduce instabilities and spurious components also in these regions.

Journal of the American College of Cardiology, 2005

To test whether left ventricular (LV) dysfunction affecting type 1 diabetic-uremic patients was a... more To test whether left ventricular (LV) dysfunction affecting type 1 diabetic-uremic patients was associated with abnormal heart high-energy phosphates (HEPs) and to ascertain whether these alterations were also present in recipients of kidney or kidney-pancreas transplantation. BACKGROUND Heart failure is the major determinant of mortality in patients with diabetic uremia. Both uremia and diabetes induce alterations of cardiac HEPs metabolism. METHODS Magnetic resonance imaging and phosphorous magnetic resonance spectroscopy of the LV were performed in the resting state by means of a 1.5-T clinical scanner. Eleven diabeticuremic patients, 5 nondiabetic patients with uremia, 11 diabetic recipients of kidney transplantation, and 16 diabetic recipients of combined kidney-pancreas transplantation were studied in a cross-sectional fashion. Eleven nondiabetic recipients of kidney-only transplant and 13 healthy subjects served as control groups. RESULTS Uremic patients had higher LV mass, diastolic dysfunction, and lower phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio in comparison with recipients of kidney-pancreas or nondiabetic recipients of kidney transplant. In diabetic recipients of kidney transplant the PCr/ATP ratio was higher than in uremic patients but was lower than in the controls. Recipients of combined kidney-pancreas transplant had a higher ratio than uremic patients but no difference was found in comparison with controls. CONCLUSIONS Altered resting myocardial HEPs metabolism may contribute to LV dysfunction in diabetic-uremic patients. In diabetic recipients of kidney transplantation, a certain degree of LV metabolic and functional impairment was found. In combined kidney-pancreas recipients the resting LV metabolism and function were not different than in controls. (

Journal of Neurology, Neurosurgery & Psychiatry, 2006

Magnetic resonance imaging (MRI) studies have demonstrated that patients with myotonic dystrophy ... more Magnetic resonance imaging (MRI) studies have demonstrated that patients with myotonic dystrophy type 1 (DM1) exhibit gray and white matter abnormalities that are correlated with various genetic and neuropsychological measures. However, few MRI studies have focused on the correlations between brain abnormalities and overall motor function including gait performance. Here, we investigated the correlations between brain abnormalities, as assessed with MRI including diffusion tensor imaging (DTI), and motor performance, as assessed with the Medical Research Council sum score (MRCSS), 6-minute walk test (6MWT), and hand grip power, in patients with DM1. Eighteen patients with DM1 and twenty healthy controls participated in this study. The MRCSS and 6MWT reflect patients' general motor performance, particularly gait, while hand grip reflects the presence of myotonia. We found significant relationships between DTI parameters in the corticospinal tract (CST) and genetic factors and motor performance in patients with DM1. These findings suggest that CST involvement reflecting deterioration of the motor tracts may play a significant role in clinical myotonia. Further, a direct relationship between the cortical gray matter volume and DTI measures in the CST suggests that white matter abnormalities in the CST are strongly associated with volume reductions in the sensorimotor cortex of patients with DM1. Myotonic dystrophy type 1 (DM1; OMIM: #160900) is a multisystem disorder that affects the muscles, eyes, heart, endocrine system, and central nervous system. It is caused by the abnormal expansion of unstable CTG trinucleotide repeats in the 3′-untranslated region of the myotonic dystrophy protein kinase gene (DMPK), which results in the intranuclear accumulation of mutated and mis-spliced transcripts, leading to an RNA gain of toxic function 1,2. Furthermore, recent pathological studies have shown the presence of neurofibrillary tangles, which may explain the brain abnormalities that are observed in patients with DM1 3-5. Many previous magnetic resonance imaging (MRI) studies have revealed the presence of brain abnormalities in patients with DM1, including abnormalities in brain volume, cortical thickness, and white matter; several studies have also found that the structural abnormalities in gray and white matter were correlated with patients' clinical and neuropsychological data 6-17. However, most of these previous MRI studies focused on the correlations

International Journal of Cardiology, 2012

Background: This study was performed to assess left ventricular (LV) energy metabolism and functi... more Background: This study was performed to assess left ventricular (LV) energy metabolism and function in patients with type 1 diabetes with or without overt microvascular complications. Methods: We performed cardiac Magnetic Resonance Imaging (MRI) and 31 P spectroscopy (MRS) in 24 patients with overt microvascular complications and in 15 carefully selected patients without complications in spite of a long duration of the disease (N 20 years) and matched for anthropometric features. 31 healthy subjects served as a control group. Results: Systolic function was preserved in all study subjects. Patients with overt complications showed a higher LV wall mass/end diastolic volume ratio and altered parameters of diastolic function when compared to patients without complications and to controls. They were also characterized by lower PCr/ATP ratio (a recognized marker of energy metabolism). No effect of HbA1c was detected within groups. Conclusions: In patients with type 1 diabetes 1) overt microvascular complications were associated with altered LV geometry, diastolic function and energy metabolism 2) in patients without complications and duration of disease N 20 years no association with these alterations were found despite poor glycemic control. The features of this highly selected subgroup of patients demonstrated that long lasting chronic hyperglycemia per se is not sufficient to induce abnormality of cardiac energy metabolism and that additional yet to be identified (metabolic or genetic) factors must be important contributing factors.

European Urology, 2003

Objectives: To evaluate the in vivo effect of apomorphine sublingual versus placebo on cortical a... more Objectives: To evaluate the in vivo effect of apomorphine sublingual versus placebo on cortical and subcortical brain activation during video sexual stimulation. Methods: Ten patients with psychogenic erectile dysfunction and six potent controls underwent functional magnetic resonance of the brain during video sexual stimulation after the administration of either apomorphine sublingual 4 mg or placebo following a randomized, double blind design. Functional magnetic resonance sessions were performed with a 7-day interval. Results: In potent controls, viewing erotic versus neutral films induced bilateral activations in a network of occipitoparietal and temporal inferior regions, in dorsolateral and premotor frontal cortex, in anterior temporal limbic areas and the thalamus, which were comparable to the patient activations during erotic stimulation in the placebo condition. However, a striking difference was found in patients, who demonstrated a significant and extended activation in the cingulate gyrus, frontal mesial and frontal basal cortex, bilaterally, in comparison with potent controls. These activated neural systems were modulated by apomorphine administration which produced a picture that was similar to the one seen in potent controls. In patients with psychogenic erectile dysfunction apomorphine sublingual caused an increase in the extension of the activated networks, plus additional activation foci in subcortical and deep structures, namely in the nucleus accumbens, hypothalamus and mesencephalon: this activation was greater than that seen with placebo. Interestingly, a down-regulation in the frontal basal and temporal limbic cortex was present as shown by a decrease of functional magnetic resonance imaging signal reflecting a deactivation of these regions. Conclusions: Apomorphine significantly enhances the activation of cortical and subcortical brain function during video sexual stimulation. Patients with psychogenic erectile dysfunction may have an underlying functional abnormality of the brain acting as a previously unrecognised aetiological factor.

Diabetes Care, 2004

OBJECTIVE—This study was performed to ascertain whether insulin resistance with respect to protei... more OBJECTIVE—This study was performed to ascertain whether insulin resistance with respect to protein metabolism is an additional primary metabolic abnormality affecting insulin-resistant offspring of type 2 diabetic parents, along with insulin resistance with respect to glucose and lipid metabolism. RESEARCH DESIGN AND METHODS—We studied 18 young, nonobese offspring of type 2 diabetic parents and 27 healthy matched (by means of dual-energy X-ray absorption) individuals with the bolus plus continuous infusion of [6,6-2H2]glucose and [1-13C]leucine in combination with the insulin clamp (40 mU · m–2 · min−1). RESULTS—Fasting plasma leucine, phenylalanine, alanine, and glutamine concentrations, as well as the glucose and leucine turnover (reciprocal pool model: 155 ± 10 vs. 165 ± 5 μmol · kg lean body mass–1 · h−1 in offspring of type 2 diabetic patients and healthy matched individuals, respectively), were also not different. During the clamp, glucose turnover rates were significantly red...

Cerebral Cortex, 2007

Grammatical class is a fundamental property of language, and all natural languages distinguish be... more Grammatical class is a fundamental property of language, and all natural languages distinguish between nouns and verbs. Brain activation studies have provided conflicting evidence concerning the neural substrates of noun and verb processing. A major limitation of many previous imaging studies is that they did not disentangle the impact of grammatical class from the differences in semantic correlates. In order to tease apart the role of semantic and grammatical factors, we performed a functional magnetic resonance imaging study presenting Italian speakers with pictures of events and asked them to name them as 1) Infinitive Verb (e.g., mangiare [to eat]); 2) Inflected Verb (e.g., mangia [she/he eats]); and 3) Action Noun (e.g., mangiata [the eating]). We did not find any verb-specific activation. However, reliable left inferior frontal gyrus (IFG) activations were found when contrasting the Action Noun with the Infinitive Verb condition. A second-level analysis indicated then that activation in left IFG was greatest for Action Nouns, intermediate for Inflected Verbs, and least for Infinitive Verbs. We conclude that, when all other factors are controlled, nouns and verbs are processed by a common neural system. In the present case, differences in left IFG activation emerge as a consequence of increasing linguistic and/or general processing demands.

BOLLETTINO-LEGA ITALIANA CONTRO L EPILESSIA, 2003

Cerebral Cortex, 2004

Using transcranial magnetic stimulation (TMS), we addressed the contribution of both hemispheres ... more Using transcranial magnetic stimulation (TMS), we addressed the contribution of both hemispheres to the visuomotor control of each hand. The subjects had to press one of two buttons as quickly as possible after the go-signal. A precue preceding this conveyed full, partial or no advance information (hand and/or button), such that reaction time (RT) shortened with increasing amount of information. We gave TMS over each hemisphere at various time intervals (100-350 ms) after the go-signal and before the expected onset of response, and measured its effect on RT, movement time (MT) and error rate. At short intervals (100-200 ms), left hemisphere TMS delayed RT and prolonged MT of both hands, while right hemisphere TMS delayed RT only of the right hand, without affecting error rates. At long intervals (250-350 ms), TMS produced slightly more pronounced RT delays of the contralateral hand. RT was delayed more if the precues were less informative. The results suggest the importance of interhemispheric transmission of visuomotor information for motor implementation. The right hemisphere may play a role mainly in calculating target and effector information, determining RT, while the left hemisphere may play a role in elaborating the motor program and determining MT.

Diabetes Care, 2007

OBJECTIVE—Fatty liver may be involved in the pathogenesis of type 2 diabetes. Physical exercise i... more OBJECTIVE—Fatty liver may be involved in the pathogenesis of type 2 diabetes. Physical exercise is a tool to improve insulin sensitivity, but little is known about its effect on intrahepatic fat (IHF) content. The purpose of this study was to examine the association of habitual physical activity, insulin resistance, and adiponectin with IHF content. RESEARCH DESIGN AND METHODS—Participants were 191 (77 female and 114 male) apparently healthy, nonalcoholic individuals (aged 19–62 years; BMI 17.0–35.5 kg/m2). IHF content was assessed in a quantitative fashion and noninvasively as a continuous variable by means of 1H magnetic resonance spectroscopy (MRS), and habitual physical activity was assessed by means of a questionnaire. Fatty liver was defined as IHF content of >5% wet weight, and insulin sensitivity was estimated using the computer homeostasis model assessment (HOMA)-2 indexes. RESULTS—A reduced prevalence of fatty liver in the quartile of the most physically active individu...

NeuroImage, 2003

We report a presurgical fMRI study and a longitudinal behavioral and structural MRI study in a 26... more We report a presurgical fMRI study and a longitudinal behavioral and structural MRI study in a 26-year-old right-handed woman with drug-resistant epilepsy of the supplementary motor region with cytoarchitectural dysplasia and minimal cortico-subcortical gliotic damage. fMRI scans were acquired during a silent phonemic verbal fluency task (VF), an automatic counting task (CT), and a finger-tapping motor task (MT). These were all compared with rest. Presurgical neuropsychological assessment was substantially normal with only a minor deficit in the domain of visuo-constructive and complex motor-planning skills. Noticeably, performance on phonemic verbal fluency was normal. Presurgical fMRI results revealed a normal specialization of left SMA and pre-SMA, including a fine-grained somatotopy for mouth and hand representations despite epilepsy. Immediately after surgical removal of the epileptogenic zone (the posterior third of the superior and middle frontal gyri including pre-SMA and part of SMA, and part of the anterior cingulate region-all of which were active presurgically at the fMRI tests), the patient suffered from transcortical motor aphasia temporarily. One year after surgery, she still showed impaired performance in the verbal fluency tasks while naming and comprehension were recovered. The patient was now free from seizures. This fMRI study supports the case that repeated seizures per se may not be sufficient to alter the distribution of neural representations of cognitive function. Selective behavioral impairment after surgical removal of brain areas that were activated during presurgical fMRI permits us to establish a causal link between these activations and task performance. This link could not have been made on the basis of activation patterns or lesion data taken on their own. These findings support the case that some epileptic patients may represent a unique opportunity for cognitive neuroscience studies.

Sleep, 2014

Study Objectives: Obstructive sleep apnea (OSA) is commonly associated with cognitive and functio... more Study Objectives: Obstructive sleep apnea (OSA) is commonly associated with cognitive and functional deficits, some of which are resolved after continuous positive airway pressure (CPAP) treatment. The investigation of brain structural changes before and after treatment could provide deep insights into the pathogenesis and the reversibility of this disorder. We hypothesized that severe OSA patients would have altered white matter (WM) integrity and cognition and that treatment would improve both the structural damage and the cognitive impairment. Design: Prospective clinical study.