Alessandro Giordano

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.

Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis

Gallium-68 somatostatin receptor (SMSR) positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) are valuable diagnostic tools for patients with neuroendocrine tumours (NETs). To date, a meta-analysis about the diagnostic accuracy of these imaging methods is lacking. Aim of our study is to meta-analyse published data about the diagnostic performance of SMSR PET or PET/CT in patients with thoracic and/or gastroenteropancreatic (GEP) NETs. A comprehensive computer literature search of studies published in PubMed/MEDLINE, Scopus and Embase databases through October 2011 and regarding SMSR PET or PET/CT in patients with NETs was carried out. Only studies in which SMSR PET or PET/CT were performed in patients with thoracic and/or GEP NETs were selected (medullary thyroid tumours and neural crest derived tumours were excluded from the analysis). Pooled sensitivity, pooled specificity and area under the ROC curve were calculated to measure the diagnostic accuracy of SMSR PET and PET/CT in NETs. Results: Sixteen studies comprising 567 patients were included in this meta-analysis. The pooled sensitivity and specificity of SMSR PET or PET/CT in detecting NETs were 93% (95% confidence interval [95% CI]: 91–95%) and 91% (95% CI: 82–97%), respectively, on a per patient-based analysis. The area under the ROC curve was 0.96. In patients with suspicious thoracic and/or GEP NETs, SMSR PET and PET/CT demonstrated high sensitivity and specificity. These accurate techniques should be considered as first-line diagnostic imaging methods in patients with suspicious thoracic and/or GEP NETs.

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.

Development and external validation of a predictive model for pathological complete response of rectal cancer patients including sequential PET-CT imaging

PURPOSE To develop and validate an accurate predictive model and a nomogram for pathologic complete response (pCR) after chemoradiotherapy (CRT) for rectal cancer based on clinical and sequential PET-CT data. Accurate prediction could enable more individualised surgical approaches, including less extensive resection or even a wait-and-see policy. METHODS AND MATERIALS Population based databases from 953 patients were collected from four different institutes and divided into three groups: clinical factors (training: 677 patients, validation: 85 patients), pre-CRT PET-CT (training: 114 patients, validation: 37 patients) and post-CRT PET-CT (training: 107 patients, validation: 55 patients). A pCR was defined as ypT0N0 reported by pathology after surgery. The data were analysed using a linear multivariate classification model (support vector machine), and the models performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS The occurrence rate of pCR in the datasets was between 15% and 31%. The model based on clinical variables (AUC(train)=0.61±0.03, AUC(validation)=0.69±0.08) resulted in the following predictors: cT- and cN-stage and tumour length. Addition of pre-CRT PET data did not result in a significantly higher performance (AUC(train)=0.68±0.08, AUC(validation)=0.68±0.10) and revealed maximal radioactive isotope uptake (SUV(max)) and tumour location as extra predictors. The best model achieved was based on the addition of post-CRT PET-data (AUC(train)=0.83±0.05, AUC(validation)=0.86±0.05) and included the following predictors: tumour length, post-CRT SUV(max) and relative change of SUV(max). This model performed significantly better than the clinical model (p(train)<0.001, p(validation)=0.056). CONCLUSIONS The model and the nomogram developed based on clinical and sequential PET-CT data can accurately predict pCR, and can be used as a decision support tool for surgery after prospective validation.

Comparison of 18F-DOPA, 18F-FDG and 68Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma

PurposeTo retrospectively evaluate and compare 18F-FDG, 18F-DOPA and 68Ga-somatostatin analogues for PET/CT in patients with residual/recurrent medullary thyroid carcinoma (MTC) suspected on the basis of elevated serum calcitonin levels.MethodsIncluded in the study were 18 patients with recurrent MTC in whom functional imaging with the three tracers was performed. The PET/CT results were compared on a per-patient basis and on a per-lesion-basis.ResultsAt least one focus of abnormal uptake was observed on PET/CT in 13 patients with 18F-DOPA (72.2% sensitivity), in 6 patients with 68Ga-somatostatin analogues (33.3%) and in 3 patients with 18F-FDG (16.7%) (p < 0.01). There was a statistically significant difference in sensitivity between 18F-DOPA and 18F-FDG PET/CT (p < 0.01) and between 18F-DOPA and 68Ga-somatostatin analogue PET/CT (p = 0.04). Overall, 72 lesions were identified on PET/CT with the three tracers. 18F-DOPA PET/CT detected 85% of lesions (61 of 72), 68Ga-somatostatin analogue PET/CT 20% (14 of 72) and 18F-FDG PET/CT 28% (20 of 72). There was a statistically significant difference in the number of lymph node, liver and bone lesions detected with the three tracers (p < 0.01). In particular, post-hoc tests showed a significant difference in the number of lymph node, liver and bone lesions detected by 18F-DOPA PET/CT and 18F-FDG PET/CT (p < 0.01 for all the analyses) and by 18F-DOPA PET/CT and 68Ga-somatostatin analogue PET/CT (p < 0.01 for all the analyses). The PET/CT results led to a change in management of eight patients (44%).Conclusion18F-DOPA PET/CT seems to be the most useful imaging method for detecting recurrent MTC lesions in patients with elevated serum calcitonin levels, performing better than 18F-FDG and 68Ga-somatostatin analogue PET/CT. 18F-FDG may complement 18F-DOPA in patients with an aggressive tumour.

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.

New trends in parathyroid scintigraphy

Abstract. The paper focusses on the recent advances in parathyroid imaging in both diagnostic and surgical fields which justify the present favourable trend towards a considerable expansion of nuclear medicine applications in this area. The main methodological advances in parathyroid scintigraphy are the rebirth of the dual-tracer (subtraction) technique with technetium-99m sestamibi, the possibility of also using 99mTc-tetrofosmin within a dual-tracer (subtraction) methodology and the more extensive use of single-photon emission tomography, which the authors believe will become the standard methodology. The indications for parathyroid scintigraphy have been affected by advances in hyperparathyroidism surgery, including wider use of unilateral neck exploration and of minimally invasive radioguided surgery. As these techniques can only be performed in hyperparathyroid patients with a single adenoma, careful pre-operative assessment is required, and parathyroid scintigraphy undoubtedly is the most accurate localisation method. To date, the majority of papers have also demonstrated the cost-effectiveness of scintigraphically guided limited neck surgery. The authors conclude that: (1) parathyroid scintigraphy can be recommended not only in persistent or recurrent hyperparathyroidism but also in hyperparathyroid patients prior to first surgery; (2) scintigraphy should always be performed by applying the most accurate technique available because reliable scintigraphy gains or reinforces the surgeons trust, reliably guides cost-effective operative strategies and justifies the recognition of new potential diagnostic indications.

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.

MIBG scintigraphy in differential diagnosis of Parkinsonism: a meta-analysis

ObjectiveDifferential diagnosis between Parkinson’s disease (PD) and other Parkinsonism using clinical criteria or imaging methods is often difficult. The purpose of this study is to systematically review and meta-analyze published data about the diagnostic performance of myocardial innervation imaging using 123I-metaiodobenzylguanidine (MIBG) scintigraphy in differential diagnosis between PD and other Parkinsonism.MethodsA comprehensive computer literature search of studies published through March 2011 regarding MIBG scintigraphy in patients with PD and other Parkinsonism was performed in PubMed/MEDLINE and Embase databases. Only studies in which MIBG scintigraphy was performed for differential diagnosis between PD and other Parkinsonism were selected. Pooled sensitivity, pooled specificity and area under the ROC curve were calculated to measure the accuracy of MIBG scintigraphy in differential diagnosis between PD and other Parkinsonism.ResultsNineteen studies comprising 1,972 patients (1,076 patients with PD, 117 patients with other Lewy body diseases and 779 patients with other diseases) were included in this meta-analysis. The pooled sensitivity of MIBG scintigraphy in detecting PD was 88% (95% CI 86–90%); the pooled specificity of MIBG scintigraphy in discriminating between PD and other Parkinsonism was 85% (95% CI 81–88%). The area under the ROC curve was 0.93.ConclusionsIn patients with clinically suspected PD, myocardial innervation imaging demonstrated high sensitivity and specificity. MIBG scintigraphy is an accurate test in this setting. Nevertheless, possible causes of false-negative and false-positive results should be kept in mind when interpreting the scintigraphic results.

Usefulness of whole-body fluorine-18-fluorodeoxyglucose positron emission tomography in patients with large-vessel vasculitis: a systematic review

The objective of this study is to systematically review the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) with fluorine-18-fluorodeoxyglucose (FDG) in patients with large-vessel vasculitis (LVV). A comprehensive literature search of published studies through April 2011 in PubMed/MEDLINE and Scopus databases regarding whole-body FDG-PET and PET/CT in patients with LVV was performed. We identified 32 studies including 604 LVV patients. The main findings of these studies are presented. The conclusions are the following: (1) FDG-PET and PET/CT are useful imaging methods in the initial diagnosis and in the assessment of activity and extent of disease in patients with LVV; (2) the correlation between FDG-PET findings and serological levels of inflammatory markers, as well as the usefulness of FDG-PET and PET/CT in evaluating treatment response, remains unclear; (3) it appears that there is a superiority of FDG-PET and PET/CT over conventional imaging methods in the diagnosis of LVV, but not in assessing disease activity under immunosuppressive treatment, in predicting relapse or in evaluating vascular complications; and (4) given the heterogeneity between studies with regard to PET analysis and diagnostic criteria, a standardization of the technique is needed.