Maria Lucia Calcagni

Abnormal Cardiac Adrenergic Nerve Function in Patients With Syndrome X Detected By [123I]Metaiodobenzylguanidine Myocardial Scintigraphy

BACKGROUND Previous studies have suggested that an abnormal cardiac adrenergic tone may have a pathophysiological role in syndrome X (effort angina, positive exercise testing, angiographically normal coronary arteries). METHODS AND RESULTS To evaluate cardiac adrenergic nerve function, we performed [123I]metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 12 patients with syndrome X and 10 control subjects. Cardiac MIBG uptake was assessed by the heart/mediastinum (H/M) ratio and by an MIBG uptake defect score (higher values=lower uptake). In syndrome X patients, we also correlated MIBG scintigraphic findings with stress myocardial perfusion as assessed by 201Tl scintigraphy. An inferior MIBG defect was observed in only 1 control subject, whereas 9 patients (P<.01) showed MIBG defects. The heart was totally or almost totally invisible on MIBG images in 5 patients, and predominantly regional defects were observed in 4. The H/M ratio was lower (1.70+/-0.6 versus 2.2+/-0.3, P=.03) and MIBG uptake defect score higher (35+/-31 versus 4+/-2, P=.003) in syndrome X patients. Reversible stress thallium perfusion defects were found in 62% of patients with MIBG defects but in no patient with normal MIBG uptake. MIBG defects persisted unchanged in 7 patients at a 5+/-3-month follow-up study. CONCLUSIONS In this study, obvious defects in global and/or regional cardiac MIBG uptake, indicating an abnormal cardiac adrenergic nerve function, were detected in 75% of patients with syndrome X. These findings strongly support the cardiac origin of chest pain in syndrome X, although the mechanisms and the pathophysiological meaning of the abnormal cardiac MIBG uptake in these patients deserve further investigation.

Cognitive Impairment in chronic obstructive pulmonary disease: a neuropsychological and spect study

Abstract. Some analogy exists between cognitive impairment in hypoxemic patients with chronic obstructive pulmonary disease (COPD) and Alzheimers disease (AD). We purposed to verify whether the analogy extends to the cerebral perfusion pattern. Ten normal subjects, 15 COPD patients with and 18 without hypoxemia, and 15 patients with mild AD matched for age and educational level underwent brain perfusion single photon emission computed tomography (SPECT) and neuropsychological assessment. Normal subjects and non hypoxemic COPD patients had comparable perfusion patterns. The average perfusion decreased from non hypoxemic to hypoxemic COPD and, then, to AD patients. Hypoperfusion of associative areas was the hallmark of AD, whereas the average perfusion of anterior cortical and subcortical regions did not distinguish AD and hypoxemic COPD patients. Both COPD groups scored higher than AD patients (p ≤ 0.01) in 13 cognitive tests but below the normal in selected tests of verbal attainment, attention and deductive thinking. Perfusion of anterior cortical and subcortical regions of the dominant hemisphere was directly correlated with the number of correctly performed neuropsychologic tests. In conclusion, anterior cerebral hypoperfusion and selected neuropsychological dysfunctions characterized hypoxemic COPD patients and could herald frontal-type cognitive decline with the worsening of the hypoxemia.

Dynamic O-(2-[18F]fluoroethyl)-L-tyrosine (F-18 FET) PET for glioma grading: assessment of individual probability of malignancy.

Purpose: (1) To investigate the diagnostic value of some O-(2-[18F]fluoroethyl)-L-tyrosine (F-18 FET) indices derived from the dynamic acquisition to differentiate low-grade gliomas from high-grade; (2) to analyze the course of tumor time-activity curves (TACs); and (3) to calculate the individual probability of a high-grade glioma using the logistic regression. Methods: Seventeen low-grade (WHO I–II) and 15 high-grade (WHO III–IV) gliomas were studied with dynamic F-18 FET PET. Regions of interests were drawn over the tumor and contralateral brain, and TACs were analyzed. We considered early standardized uptake value (SUV), middle SUV, late SUV, early-to-middle SUV tumor ratio, early-to-late SUV tumor ratio; time to peak (Tpeak), in minutes, from the beginning of the dynamic acquisition up to the maximum SUV of the tumor; and SoD (sum of the frame-to-frame differences). To assess the individual probability of high-grade, logistic regression was also used. Results: High-grade gliomas showed significantly (P < 0.0001) higher values when compared with low-grade gliomas in early SUV, early-to-middle ratio, early-to-late ratio, Tpeak, and SoD. For the grading of gliomas, the best indices were early-to-middle ratio and Tpeak providing a diagnostic accuracy of 94%. TACs analysis provided an 87% diagnostic accuracy. For individual high-grade diagnosis, the logistic regression provided 93% sensitivity, 100% specificity, and 97% accuracy. Conclusion: Early-to-middle SUV tumor ratio and Tpeak were the best indices for assessing the grading of gliomas. Since early-to-middle ratio derives from the first 35 minutes of the dynamic acquisition, the PET study could last half an hour instead of 1 hour. By logistic regression, it is possible to assess the individual probability of high-grade, useful for prognosis and treatment.

The role of positron emission tomography using carbon-11 and fluorine-18 choline in tumors other than prostate cancer: a systematic review

To systematically review published data on the role of positron emission tomography (PET) or PET/computed tomography (PET/CT) using either Carbon-11 (11C) or Fluorine-18 (18F) choline tracer in tumors other than prostatic cancer. A comprehensive literature search of studies published in PubMed/MEDLINE and Embase databases through January 2012 and regarding 11C-choline or 18F-choline PET or PET/CT in patients with tumors other than prostatic cancer was carried out. Fifty-two studies comprising 1800 patients were included and discussed. Brain tumors were evaluated in 15 articles, head and neck tumors in 6, thoracic tumors (including lung and mediastinal neoplasms) in 14, liver tumors (including hepatocellular carcinoma) in 5, gynecologic malignancies (including breast tumors) in 5, bladder and upper urinary tract tumors in 5, and musculoskeletal tumors in 7. Radiolabeled choline PET or PET/CT is useful to differentiate high-grade from low-grade gliomas and malignant from benign brain lesions, to early detect brain tumor recurrences and to guide the stereotactic biopsy sampling. The diagnostic accuracy of radiolabeled choline PET is superior compared to Fluorine-18 fluorodeoxyglucose (18F-FDG) PET in this setting. Radiolabeled choline PET or PET/CT seems to be accurate in differential diagnosis between malignant and benign thoracic lesions and in staging lung tumors; nevertheless, a superiority of radiolabeled choline compared to 18F-FDG has not been demonstrated in this setting, except for the detection of brain metastases. Few but significant studies on radiolabeled choline PET and PET/CT in patients with hepatocellular carcinoma (HCC) and musculoskeletal tumors are reported in the literature. The combination of radiolabeled choline and 18F-FDG PET increases the detection rate of HCC. The diagnostic accuracy of radiolabeled choline PET or PET/CT seems to be superior compared to 18F-FDG PET or PET/CT and conventional imaging methods in patients with bone and soft tissue tumors. Limited experience exists about the role of radiolabeled choline PET and PET/CT in patients with head and neck tumors, bladder cancer and gynecologic malignancies including breast cancer.

Clinical significance of incidental focal colorectal (18)F-fluorodeoxyglucose uptake: our experience and a review of the literature.

Aim  The aims of the present study were: (i) to evaluate the focal incidental colorectal uptake of 18F‐fluorodeoxyglucose ([18F]FDG) and to correlate it with colonoscopy and histological findings; (ii) to evaluate the relationship between the presence/absence of neoplastic disease and clinical data and the anatomical site of [18F]FDG uptake; and (iii) to compare our results with those reported for incidental colorectal uptake of [18F]FDG in the literature and those obtained from various screening programmes for colorectal cancer.

Dopamine transporter binding in depressed patients with anhedonia

Central dopaminergic dysfunction has been widely proposed as a common neurobiological correlate of the psychopathological expression of anhedonia. The dopamine transporter (DAT) is a predominantly presynaptic receptor that may play a critical role in the pathophysiology of dopaminergic transmission. The aim of our study was to evaluate DAT binding in a population of depressed patients with anhedonia. Single photon emission computed tomography (SPECT) with the radiotracer DATSCAN was used to evaluate DAT binding in 11 depressed patients with anhedonia and 9 healthy comparison subjects. Compared with healthy subjects, patients showed significantly lower DAT binding. No significant correlation was found between DAT binding ratios and scores on administered psychometric tests. These findings suggest an alteration in DAT density in depressed patients with anhedonia that may be a primary susceptibility factor or a secondary phenomenon to reduced dopamine concentration in the synaptic cleft.

Comparison of 123I-MIBG SPECT-CT and 18F-DOPA PET-CT in the evaluation of patients with known or suspected recurrent paraganglioma.

ObjectivesDetection of recurrent disease is essential for treatment planning in patients with paraganglioma. The aim of this study was to compare 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy [whole-body and single-photon emission computed tomography (SPECT) computed tomography (CT) scanning] and fluorine-18-L-dihydroxyphenylalanine positron emission tomography CT (18F-DOPA PET-CT) in the re-staging of patients with known or suspected recurrent paraganglioma. MethodsTwelve patients with known or suspected recurrent paraganglioma after initial surgery were included in the study. 18F-DOPA PET-CT and 123I-MIBG scintigraphy (whole-body and SPECT-CT scanning) were performed in all patients; the results were compared on a per patient and a per lesion basis. Cytohistology (when available) and a combination of laboratory and imaging studies and follow-up were used as reference standard; any modification in treatment planning was recorded. In all cases recurrent disease (local or distant) was confirmed by cytohistology (four cases) or at subsequent follow-up (eight cases). ResultsAll patients had positive 18F-DOPA studies (100% sensitivity) whereas nine had positive 123I-MIBG studies (75% sensitivity; P=not significant). 18F-DOPA detected 98% of lesions, whereas 38% were detected with 123I-MIBG (P=0.04). 18F-DOPA showed more lesions than 123I-MIBG in eight patients; both techniques showed the same number of lesions in two cases whereas in two patients 123I-MIBG showed a greater number of lesions. A change in treatment planning was suggested by 18F-DOPA in one patient. ConclusionThese data support the superiority of 18F-DOPA PET-CT over 123I-MIBG scintigraphy to assess disease extension in patients with recurrent paraganglioma; however, in cases with inoperable disease, 123I-MIBG maintains a unique role in allowing the selection of patients suitable for 131I-MIBG therapy.

imaging of peritoneal carcinomatosis with FDG PET-CT: diagnostic patterns, case examples and pitfalls

Early diagnosis of peritoneal spread in malignant disease is essential to prevent unnecessary laparotomies and to select the patients in whom complete cytoreduction is feasible. Although anatomic imaging is the mainstay for evaluating peritoneal seeding, small neoplastic implants can be difficult to detect with CT and MR imaging. FDG PET-CT has the potential to improve detection of peritoneal metastases as lesion conspicuity is high at PET due to low background activity and fused PET-CT offers the combined benefits of anatomic and functional imaging. Correlation of uptake modalities with the pathogenesis of intraperitoneal spread of malignancies, provides a rational system of analysis and is essential to define disease. Distinct patterns appear to predict the presence of either nodular or diffuse peritoneal pathology. Main pitfalls are related to normal physiologic activity in bowel loops and blood vessels or focal retained activity in ureters and urinary bladder. PET-CT is most suitable in patients with high tumor markers and negative or uncertain conventional imaging data and in selecting patients for complete cytoreduction. FDG PET-CT adds to conventional imaging in the detection and staging of peritoneal carcinomatosis and is a useful diagnostic tool in monitoring response to therapy and in long term follow-up.

Rhinoscintigraphy: A Simple Radioisotope Technique To Study the Mucociliary System

PURPOSE This was a radioisotope study of nasal mucociliary clearance of total and subtotal nasal obstruction. METHODS Rhinoscintigraphy was performed by insufflating 1.85 MBq (69 mCi) Tc-99m MAA in 20 patients. Six cases were regarded as the control group, because the presence of small spurs does not affect nasal patency. The remaining 14 patients had various rhinopathic conditions. Two regions of interest were selected, one in the nasal cavity and one in the pharynx. Mucociliary transport speed was calculated. RESULTS This parameter appeared to be a sensitive index for the assessment of the degree of mucociliary alteration. It showed that polyposis impairs mucociliary transport most severely, thus confirming the results of other published studies. CONCLUSIONS Rhinoscintigraphy proved to be a reliable, easily reproducible, and harmless method, so it may be used for follow-up examinations in patients who have had surgery of the nose and paranasal sinuses, and for drug therapy of rhinopathic conditions.

Prevalence of spinocerebellar ataxia type 2 mutation among Italian Parkinsonian patients

We evaluated the prevalence of the SCA2 mutation among 224 Italian patients affected by typical Parkinsonism, including 145 sporadic and 79 familial forms. Pink1, Parkin, and LRRK2 gene mutations had been excluded previously. Molecular testing for the CAG expansion at the SCA 2 locus was performed on leukocyte DNA. Cloning and sequencing of the expanded allele was performed in patients positive for the SCA2 expansion. A 38 CAG expansion was detected in 1 of 79 families studied. The proband, a male age 67, and his sister, age 69, were both affected by a benign form of L‐dopa–responsive Parkinsonism not associated with cerebellar signs. The inheritance was autosomal dominant. The CAG expansion was stable through meiotic transmission: sequence analysis showed that the CAG stretch was interrupted by 3 CAA. Our study shows that CAG expansion at the SCA 2 locus may represent a genetic cause of familial L‐dopa–responsive Parkinsonism among Italian patients. The stability of the pathological CAG expansion detected in this family was related to the presence of CAA interruptions. These findings, together with literature data, suggest that the molecular intrinsic structure of the expanded allele may modulate the phenotypic expression of the SCA2 mutation.