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Biomedical subjects

F Fazio

Publications and source records attributed to F Fazio.

At least 145 records · Page 8Linked to original sources

Brain processing of native and foreign languages.

We used positron emission tomography to study brain activity in adults while they were listening to stories in their native language, in a second language acquired after the age of seven, and in a third unknown language. Several areas, similar to those previously observed in monolinguals, were activated by the native but not by the second language. Both the second and the unknown language yielded distinct left-hemispheric activations in areas specialized for phonological processing, which were not engaged by a backward speech control task. These results indicate that some brain areas are shaped by early exposure to the maternal language, and are not necessarily activated by the processing of a second language to which they have been exposed for a limited time later in life.

Adult↗

Exercise-induced ischemic arrhythmias in patients with previous myocardial infarction: role of perfusion and tissue viability.

OBJECTIVES: This study sought to investigate whether residual viability of infarcted myocardium may play a role in the pathogenesis of exercise-induced ventricular arrhythmias. BACKGROUND: We previously showed that transient ischemia within partially infarcted areas often precipitates ventricular arrhythmias during exercise that are consistently obliterated by intravenous nitrates. METHODS: We studied 60 patients with chronic stable angina and a previous myocardial infarction. All underwent at least two consecutive exercise stress tests, coronary angiography and stress/rest myocardial perfusion tomography by Tc-99m 2-methoxy isobutyl isonitrile (MIBI). In the last 26 consecutive patients, residual viability was assessed by single-photon emission computed tomography (SPECT) using fluorine (F)-18 fluorodeoxyglucose. Perfusion and metabolic data were evaluated qualitatively by three independent observers in blinded manner. RESULTS: With exercise, 30 patients (group A) consistently developed ventricular arrhythmias (> 10 ventricular ectopic beats/min, couplets, nonsustained ventricular tachycardia); the remaining 30 patients (group B) did not. The severity of coronary artery disease (Gensini score) was similar in the two groups. Postexercise SPECT showed partial reperfusion of an infarcted area in 28 of 30 patients of group A but in only 9 of 30 of group B (p < 0.0001). Uptake of F-18 fluorodeoxyglucose was observed within the infarcted zone in 10 of 13 and 1 of 13 patients in groups A and B, respectively (p = 0.0003). CONCLUSIONS: In patients with myocardial infarction, exercise-induced ventricular arrhythmias appear to be triggered by transient ischemia occurring within a partially necrotic area containing large amounts of viable myocardium. Therefore, occurrence of arrhythmias during exercise may represent a clue to the presence of residual viability within a previously infarcted area.

Case-Control Studies↗

Varieties of progressive non-fluent aphasia.

We report four patients with progressive aphasia of the non-fluent type as the presenting clinical manifestation. The patients were included in a longitudinal study of focal progressive neuropsychological syndromes, and were periodically submitted to neuropsychological evaluations and neuroimaging studies (TC, MRI, SPET or PET). The pattern of neuropsychological impairment was in good agreement with the results of functional imaging studies, which indicated involvement of the anterior regions of the left hemisphere. The evolution of the clinical picture was extremely heterogeneous in the four patients, ranging from a relatively stable picture of transcortical motor aphasia to a severe progressive frontal lobe syndrome. Progressive non-fluent aphasia appears to be a reliable clinical marker of the localization of the pathological process; whether this is related to specific neuropathological conditions, such as Pick's disease, remains for the moment a matter of speculation.

Adult↗

Functional basis of memory impairment in multiple sclerosis: a[18F]FDG PET study.

Structural neuroimaging has been used to correlate lesional patterns with the cognitive profile of patients with multiple sclerosis (MS), especially for "frontal" dysfunction. However, a clear-cut anatomical explanation has yet to be found for the long-term memory deficit which is a hallmark of MS cognitive impairment. We have used PET to measure regional cerebral glucose metabolism (rCMRglc) in a group of 15 MS patients with involvement of verbal and/or spatial long-term memory. These patients were compared with 10 normal controls and 13 MS patients unimpaired on all neuropsychological tests. Relative to the controls, MS patients with memory deficits showed a significant bilateral reduction of rCMRglc in the hippocampus, cingulate gyrus, thalamus, associative occipital cortex, and cerebellum. Direct comparisons between patients with memory deficits and the group of unimpaired MS patients showed a metabolic reduction in the left thalamus and in both hippocampi. Seven of the memory-impaired patients also had neuropsychological signs of frontal dysfunction. These patients were compared with patients who had isolated memory deficit. Here we observed a further metabolic reduction in a number of brain regions including bilateral prefrontal cortex, inferior parietal cortex, and basal ganglia. Our findings indicate that hypometabolism of thalamic and deep cortical gray structures of the temporal lobe is associated with episodic memory dysfunction in MS. On the other hand, pathological performance on tests designed to assess frontal functions was associated with widespread reduction of glucose metabolism.

Adult↗

Localization of grasp representations in humans by PET: 1. Observation versus execution.

Positron emission tomography (PET) was used to localize brain regions that are active during the observation of grasping movements. Normal, right-handed subjects were tested under three conditions. In the first, they observed grasping movements of common objects performed by the experimenter. In the second, they reached and grasped the same objects. These two conditions were compared with a third condition consisting of object observation. On the basis of monkey data, it was hypothesized that during grasping observation, activations should be present in the region of the superior temporal sulcus (STS) and in inferior area 6. The findings in humans demonstrated that grasp observation significantly activates the cortex of the middle temporal gyrus including that of the adjacent superior temporal sulcus (Brodmann's area 21) and the caudal part of the left inferior frontal gyrus (Brodmann's area 45). The possible functional homologies between these areas and the monkey STS region and frontal area F5 are discussed.

Adult↗

Single-photon emission tomographic quantification in spherical objects: effects of object size and background.

A method was set up for single-photon emission tomographic (SPET) quantification of radioactivity concentration in small anatomical structures. The method is based on the theoretical model proposed by Kessler et al. (J. Comput Assist Tomogr 1984; 8: 514-522) describing the effects of spatial resolution (partial volume effect and spillover) on the quantification of radioactivity concentration in small spherical objects. The model was validated here in SPET, by phantom experimental measurements, in relation to object size and source/background contrast. Good agreement was found between model-predicted and SPET-measured radioactivity concentration ratios in hot spots in hot background experiments. Accuracy of the method was assessed for comparison of model-corrected and true radioactivity concentration ratios and was found to be within 8.5% over the full range of object size (9.4-36.5 mm). The good agreement found indicates that the model can be used to correct for partial volume effect and spillover in specific clinical situations, when the anatomical structure under study can be approximated by a sphere of known size (e.g. neuroreceptor and tumour studies). The method was applied to a representative SPET monoclonal antibody patient study for the quantification of radioactivity concentration in ocular melanoma.

Eye Neoplasms↗

In vivo imaging of chromogranin A-positive endocrine tumours by three-step monoclonal antibody targeting.

The detection of chromogranins (Cg) by immunohistochemistry and serology represents a new in vitro diagnostic tool for endocrine tumours. We have recently reported on the feasibility of targeting chromogranin A (CgA) for in vivo detection of pituitary adenomas by immunoscintigraphy (ISG). The scintigraphic procedure, based on an anti-CgA monoclonal antibody and on the avidin-biotin three-step method (Cg-3S-ISG), was evaluated on a group of 29 consecutive patients with known or suspected endocrine tumours other than pituitary adenomas, i.e. medullary thyroid carcinoma, carcinoid, insulinoma and parathormone- or ACTH-producing tumours. Primary tumours (10) and recurrences (16) were visualised in 26 patients, whereas conventional imaging techniques (planar radiography, computerised tomography, magnetic resonance imaging and ultrasonography) failed to detect the tumour sites in ten of the same (Cg-3S-ISG-positive) patients. Therefore, these preliminary results indicate that Cg-3S-ISG, the first immunological method able to detect endocrine tumours in vivo, has a higher diagnostic accuracy than conventional imaging techniques (93.1% compared with 65.5%).

Antibodies, Monoclonal↗

Double-blind stereo-EEG and FDG PET study in severe partial epilepsies: are the electric and metabolic findings related?

The aim of this study was to evaluate, in 16 patients with drug-resistant partial epilepsy who were waiting to undergo surgical treatment, the relation between positron emission tomography (PET) findings with fluorine-18 fluorodeoxyglucose ([18F]FDG) in the interictal state and the different stereo-electroencephalography (SEEG) patterns that characterize: (a) the epileptogenic zone (low-voltage fast-activity discharge before or concurrent with ictal clinical symptoms), (b) the irritative zone (spikes, spikes and waves, isolated or grouped in short bursts) and (c) the lesional zone (continuous, sometimes polyrhythmic slow waves or continuous delta waves or very important voltage depression). SEEG was performed following an individually defined electrode implantation strategy. Whereas at least one area of hypometabolism was detected by visual interpretation of PET/[18F]FDG images in all the subjects in the study, there was poor agreement between PET/[18F]FDG quantitative measures of regional metabolism and SEEG findings. Normal metabolic rates were found in up to 62% of the areas with abnormal SEEG activity, independent of the type of electrical activity, i.e. epileptogenic, irritative, or lesional, while abnormal metabolic rates were found in up to 23% of the areas with normal SEEG activity. In conclusion, whereas the visual interpretation of interictal studies of glucose utilization in our series of drug-resistant epileptic patients consistently allowed the localization of an area of temporal hypometabolism, the quantitative and regional metabolic analysis demonstrated that such a finding is not specifically related to any of the three very different SEEG patterns (epileptogenic, irritative, lesional) or combinations thereof. These results complement those of previous interictal and ictal single-photon emission tomographic studies and of receptor studies in epileptics, suggesting functional and biochemical heterogeneity within the interictal hypoperfused/hypometabolic area in epileptic patients, and contribute to the debate on the use and interpretation of interictal PET/[18F]FDG studies in patients with medically refractory partial seizures.

Adult↗

A procedure for wall detection in [18F]FDG positron emission tomography heart studies.

Quantitative positron emission tomography (PET) heart studies require the accurate localization of regions of interest (ROIs) on the myocardial wall (MW) and left ventricle (LV). The procedure is often inaccurate, especially when there is low tracer uptake. We implemented a data processing technique to improve the accuracy of the localization of ROIs on the MW and LV in fluorine-18 labelled deoxyglucose ([18F]FDG) PET heart studies. This technique combines transmission data, acquired before tracer administration and used for attenuation correction, and dynamic emission data (DY), acquired to obtain myocardial time-activity curves and used to calculate regional myocardial glucose utilization, to generate a new set of "transmission" images (TRDY) with enhanced contrast between MW and LV. These new transmission images identify the extravascular myocardial tissue and can be used for ROI placement. Validation of the method was performed in 25 patients, studied after an oral glucose load, by drawing irregular ROIs on three transaxial slices outlining the septum and anterior-apical and lateral wall on the last frame of the DY images (steady state) and then on the TRDY images. Two kinds of analysis were performed on a total of 225 myocardial segments: (1) mean counts per pixel in the DY images from ROIs independently drawn on DY and TRDY images were compared; (2) TRDY ROIs were copied onto DY images and repositioned in the event of mismatch between ROIs and myocardial tissue edge. Mean counts per pixel in the DY images from the original and the repositioned TRDY ROIs were compared. An excellent correlation was found in both cases (using TRDY and DY ROIs: y=0.908 x+0.068, r=0.97; using TRDY ROIs alone: y=0.975 x+0.006, r=0.99). This technique can be used for clinical applications in physiological and pathological conditions in which the myocardial [18F]FDG uptake is reduced or minimal, including diabetes and myocardial infarction.

Calibration↗

Persistent post-traumatic retrograde amnesia: a neuropsychological and (18F)FDG PET study.

We report the case of a 48-year old woman who, after a severe closed head injury, developed a severe and persistent disruption of retrograde memory, associated with a mild impairment of learning abilities. The patient's dense amnesia spared only the childhood period and included both explicit memory (autobiographical and semantic) and procedural skills. Because of her partially spared learning ability and intact language, intensive training by family members resulted in the reacquisition and retention of many autobiographical events and of some skills she had lost after the accident. Brain CT scan and MRI were normal; a PET study with (18F)FDG revealed a significant bilateral reduction of metabolism in the hippocampus and anterior cingulate cortex, suggesting a role for these structures in memory for past events.

Amnesia↗

99mTc-2GAM: a tracer for renal imaging.

We propose a renal imaging agent, the 99mTc complex of the bidentate-N,S chelate N-(mercaptoacetyl)glycine (99mTc-2GAM), with the imaging characteristics of 99mTc-DMSA but a faster kidney uptake; chemical evidence supports the formulation of 99mTc-2GAM as [Tc(v)(O)(GAM)2]-. After biodistribution and toxicity studies in animals, 99mTc-2GAM was evaluated in five normal volunteers. 99mTc-2GAM is rapidly cleared from the blood (t1/2 = 9 min) and 50% of the ID is excreted in the urine in the first 2 h. Dynamic data show a rapid renal uptake that increases up to 1 h with no significant wash-out between 1 and 8 h. The uptake in each kidney ranges from 11.3% to 20.7% ID. Low, stable liver uptake is observed. No significant activity is detected in other organs. We showed no differences between 99mTc-2GAM and 99mTc-DMSA compared in three patients with unilateral kidney disease. We conclude that 99mTc-2GAM has good practical and dosimetric features for renal imaging.

Adult↗

Pretargeted immunoscintigraphy in patients with medullary thyroid carcinoma.

To evaluate the use of pretargeted immunoscintigraphy (ISG) in the diagnosis and follow-up of patients with medullary thyroid carcinoma (MTC), we studied 25 patients with histologically proven disease; ISG was repeated after surgery in two patients. The antibody, either an anticarcinoembryonic antigen (CEA) or an antichromogranin A (CgA) biotinylated monoclonal antibody (MAb) or a cocktail of the two biotinylated MAbs was first injected. After 24 h, avidin was administrated i.v., followed by 111In-labelled biotin 24 h later. Fifty-two lesions were visualised. Six primary tumours, diagnosed by increased calcitonin levels, were all correctly diagnosed; 47 recurrences, also suspected by blood tumour markers, were detected and confirmed by cytology or histology. In one case, single photon emission tomography allowed the detection of small lymph nodes with a diameter of 4-7 mm. These lesions, not judged neoplastic by ultrasound, were confirmed to be neoplastic by fine needle aspiration. Pretargeted ISG correctly localises primary tumours and recurrences in MTC patients, when the only marker of relapse is serum elevation of calcitonin. With this three-step pretargeting method, cocktails of potentially useful MAbs can be used, avoiding false-negative studies that may occur when CEA or CgA are not expressed.

Adolescent↗

High prevalence of the thallium-201 reverse redistribution phenomenon in patients with syndrome X.

OBJECTIVE: To evaluate the stress-myocardial perfusion pattern in patients with angina, positive exercise test and angiographically smooth coronary arteries (syndrome X). DESIGN: Prospective study. PATIENTS AND METHODS: Twenty-five consecutive patients (seven males, mean age 54 +/- 8 years) with typical angina, positive exercise test, normal coronary arteries and no inducible spasm, underwent stress-redistribution thallium-201 myocardial perfusion scintigraphy. Thirty-two consecutive patients (14 males, mean age 49 +/- 7 years) with atypical chest pain and negative exercise test, undergoing stress-redistribution thallium scan, served as controls. RESULTS: Exercise was discontinued for angina and/or ST-segment depression after 12 +/- 3 min. Thallium stress images revealed 40 hypoperfused segments in 27 patients (77%); after 4 h, 16 of these segments had completely normalized, 10 remained unchanged, six exhibited partial reperfusion and eight worsened. Twenty-four patients (69%) exhibited thallium reverse redistribution in 33 segments. Thirty-four patients (97%) had at least one hypoperfused segment in one of the two scintigraphic phases. Of the 24 patients with reverse redistribution, eight also underwent stress-rest 99m Tc-MIBI SPECT: six exhibited reduced tracer uptake that was present at rest, but not on stress images, in the same segments showing thallium reverse redistribution. Thallium stress images revealed four hypoperfused segments in three controls (9%); at redistribution, one segment normalized, two remained unchanged and one exhibited partial reperfusion. Additionally, there were four new underperfused segments appearing on redistribution in four patients (13%). Overall, there were seven controls (22%) with at least one hypoperfused myocardial segment in one of the two scintigraphic phases. CONCLUSIONS: Our study confirms that perfusion abnormalities are present in most syndrome X patients. Additionally, the data show that reverse redistribution (a perfusion defect that develops or becomes more evident on delayed imaging) is a common finding in these patients. The mechanisms of the phenomenon remain obscure: we suggest that it is due to inhomogeneous perfusion, and the hyperaemic response induced by exercise masks resting underperfusion of certain areas.

Adult↗

Reverse perfusion pattern of Tc-99m MIBI heralding the development of myocardial infarction.

In a patient with sporadic atypical chest pain associated with dyspnea, stress Tc-99m MIBI imaging showed normal perfusion and inferoposterior hypoperfusion on the resting study. Although this reverse perfusion pattern was considered artifactual, the patient later had an acute myocardial infarction involving the same areas. Postinfarction stress Tc-99m MIBI imaging showed a nonreversible defect in the same area that, in the earlier study, showed a reverse perfusion pattern. The authors hypothesize that partial stenosis of the related artery with some nontransmural myocardial necrosis at the time of the initial study may be a possible cause of this peculiar Tc-99m MIBI perfusion pattern.

Aged↗

Glucose metabolism and pathological findings in uveal melanoma: preliminary results.

The aims of this study were to assess the sensitivity of positron emission tomography (PET) using [18F]fluorodeoxyglucose (18F-FDG) in the detection of uveal melanoma, and to establish the relationship between pre-operative 18F-FDG uptake and a number of pathological features of uveal melanoma. Twenty consecutive patients with a clinical diagnosis of uveal melanoma were enrolled in the study. 18F-FDG uptake was assessed in all subjects and the following parameters were assessed in 11 enucleated subjects: the mitotic index, the MIB-1 proliferating cell index, number of epithelioid cells, largest tumour diameter, tumoral necrosis and inflammatory infiltration. Tumours with a diameter less than 7.5 mm were not detected by PET, possibly because of limited spatial resolution, and only 7 of 12 tumours with a diameter greater than 7.5 mm were detected. With tumours greater than 7.5 mm in diameter, PET and 18F-FDG allow two subgroups to be distinguished: those with high and those with low glucose consumption. Apart from tumour size, 18F-FDG uptake was not related to the pathological features examined. We hypothesize that 18F-FDG uptake may be related to the ratio of viable to non-viable cells, or to the hypoxic cell fraction within the tumour.

Adult↗

Basal ganglia and thalamo-cortical hypermetabolism in patients with spasmodic torticollis.

UNLABELLED: The basal ganglia are thought to be involved in the primary dystonias, largely because of the repeated demonstration of neuropathological changes in these nuclei in the secondary dystonias. A hyperactivity of a network involving basal ganglia has been suggested in experimental animal dystonia. To test this hypothesis in humans, we studied the functional correlates of primary cervical dystonia using [18F]FDG and PET. MATERIAL AND METHODS: Regional cerebral glucose metabolism (rCMRglc) was measured in 10 patients with idiopathic torticollis (6 drug-free and 4 drug-naive) and in 15 normal controls, using 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET). RESULTS: A significant hypermetabolism in the basal ganglia, thalamus, premotor-motor cortex and cerebellum in the patients compared with normal controls was found. The patients were correctly assigned to their clinical category by a discriminant function analysis with a total accuracy of 96%. CONCLUSION: The results support the hypothesis that a dysfunction of a subcortical-cortical motor network may play a role in the pathogenesis of focal dystonia, in agreement with the experimental dystonia models.

Adult↗

Three-step immunoscintigraphy with anti-chromogranin A monoclonal antibody in tumours of the pituitary region.

In the present paper we evaluated the ability of pretargeted immunoscintigraphy (ISG) with antichromogranin A (CgA) monoclonal antibody (Mc-ab A11) in visualizing pituitary masses. The results obtained in 23 patients are described along with those of [111In]pentetreotide scintigraphy (Octreoscan) in 18 cases. Positive ISG was obtained in 9/11 (82%) non-functioning, 1/4 growth hormone-, 1/2 prolactin-, 1/2 thyrotropin-, 1/1 follicle-stimulating hormone-, 0/1 adrenocortico-trophin-secreting pituitary adenomas. In one patient with a positive ISG scan of a non-functioning pituitary adenoma, an associated neurinoma of the acoustic nerve was not imaged. The same occurred in one patient with a pituitary deposit from a mammary carcinoma and in another one with a cyst of the Rathke's pouch. Chromogranin A immunohistochemistry, carried out in 10 tumours, was positive in eight pituitary adenomas and negative in two non-adenomatous lesions. A concordant ISG occurred in all cases except for two pituitary adenomas: one cystic and necrotized and one post-operative remnant very small in size. In 18 patients with pituitary adenoma both ISG and Octreoscan were positive in 61% of cases but with a different distribution among tumours. At variance with ISG, Octreoscan visualized only 5/10 (50%) non-functioning pituitary adenomas and all (4/4) somatotropinomas. In conclusion, ISG is able to image pituitary tumours and particularly non-functioning pituitary adenomas. In this respect, it may be helpful in discriminating non-neuroendocrine masses of the pituitary region from non-functioning pituitary adenomas.

Adolescent↗

Detection of prosthetic vascular graft infection using avidin/indium-111-biotin scintigraphy.

UNLABELLED: Prosthetic vascular graft infection, though rare, carries high morbidity and mortality rates; therefore, timely diagnosis is important. Patients, however, often present with vague symptoms, and radiological investigations are frequently inconclusive. These factors may lead to prolonged periods of observation and hospitalization, with the resultant increase in costs and complication rates, before reaching a final diagnosis. This prospective study evaluates the use of nonspecific avidin/111In-biotin imaging in diagnosing prosthetic vascular graft infection. METHODS: Twenty-five patients with a total of 29 grafts were investigated. Eighteen patients (19 grafts) had low probability of disease, whereas the remaining 7 patients (10 grafts) warranted surgical exploration based on clinical, laboratory or radiological evidence. Avidin was first injected intravenously and then followed 24 hr later by administration of 111In-biotin. Whole-body images were obtained 10 min and 2 hr postinjection of 111In-labeled biotin. SPECT imaging was performed 1 hr postinjection. Increased uptake along part or the whole length of the graft was considered evidence of graft infection. RESULTS: Avidin/111In-biotin scintigraphy correctly identified all infected grafts, as confirmed by culturing surgical specimens. In contrast, infection was correctly excluded in all but one of the grafts, and long-term follow-up was used to assess the presence of infection in patients who did not undergo surgical intervention. CONCLUSION: Avidin/111In-biotin scintigraphy is a simple and accurate imaging method for the routine diagnosis of vascular graft infection, and it may have a role in identifying the disease process in its initial stages, thus improving prognosis.

Aged↗