Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy.

OBJECTIVES: To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. METHODS: This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. RESULTS: The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P < 0.001) in enhancement between benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. CONCLUSIONS: Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. KEY POINTS: • Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. • Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. • CEUS may be a potentially useful adjunct in assessing thyroid nodules.

Diagnostic imaging in Merkel cell carcinoma: lessons to learn from 16 cases with correlation of sonography, CT, MRI and PET.

OBJECTIVE: The authors report imaging findings in a series of 16 patients with MCC, a rare tumour which is often managed primarily by a dermatologist. To our knowledge, no equivalent series of MCC has been described in the nuclear medicine literature. MATERIAL AND METHODS: In this IRB-approved retrospective noncomparative case series 16 patients with biopsy-proven Merkel cell carcinoma were included between January 1999 and October 2007. Twenty-nine whole body PET scans (18F-FDG n=24, 18F-FDOPA n=5) in 16 patients were retrospectively reviewed with regard to tracer uptake in six anatomical sites per patient. For 127/144 of FDG-PET evaluated regions and 68/144 of regions depicted by conventional imaging methods, a valid standard of reference could be obtained. A combined standard of reference was applied, which consisted of histopathology (lymphadenectomy or biopsy) or clinical or radiological follow-up for at least 12 months. RESULTS: the mean FDG uptake over the clinicopatholigical verified FDG avid areas was 4.7 SUV (1.5-9.9 SUV). The region based assessment of diagnostic value, in consideration of the standard of reference, resulted in a sensitivity of 85.7% and a specificity of 96.2% of FDG-PET (n=127) and in a combined sensitivity of 95.5% and a specificity of 89.1% for morphological imaging methods (n=68). Differences between methods did not reach statistical significance (p=1.00, p=0.18). CONCLUSIONS: FDG-PET is a highly useful whole body staging method of comparable value compared to conventional imaging methods with restricted field of view. The lessons learned from case series are discussed.

SPECT/CT fusion imaging in radionuclide cisternography for localization of liquor leakage sites.

OBJECTIVE: We report our experience with radionuclide cisternography (RC) with 111In-diethylenthriamine penta-acetic acid (DTPA) using a computed tomography (CT) mounted hybrid gamma camera in patients with cerebrospinal liquor leakage. METHODS: SPECT/CT fusion imaging was performed in case of suspected tracer egress on planar or SPECT images in order to obtain a detailed correlation of the leakage site. RESULTS: Leakage was detected in all 3 patients. Using SPECT/CT, the extradural tracer accumulation could be correlated to an anatomical structure, which had not been possible by evaluation of the scintigraphic studies alone. CONCLUSION: Introducing SPECT/CT for radionuclide cisternography seems to be a valuable tool to facilitate the diagnosis of cerebrospinal liquor leakage.

Vascular endothelial growth factor in thyroid cyst fluids.

BACKGROUND: The pathogenesis of cystic thyroid nodules is incompletely understood. Based on the assumption that vascular endothelial growth factor (VEGF) may play an important role in the pathogenesis of thyroid cyst fluid, we investigated the VEGF concentration in cyst fluids of thyroid lesions. DESIGN: Cyst fluids from 24 patients (age 31-84 years) were obtained using ultrasound-guided fine-needle aspiration. The patients' cystic thyroid nodules were of different origins. METHODS: Thyroid and cyst volumes were determined using high-resolution ultrasonography. VEGF concentrations were determined using a solid-phase enzyme-linked immunosorbent assay (ELISA). RESULTS: Differing elevated VEGF concentrations were demonstrated in cyst fluids of thyroid nodules of varied origins. The VEGF concentration in cyst fluid of patients with adenomatous goiter was significantly higher (P < 0.05) than that in thyroid nodules with cystic degeneration. The highest level of VEGF was found in bloody cyst fluid when compared with levels in other cyst fluids (P < 0.05). Interestingly, there was significant correlation (P < 0.01) between thyroid volume and VEGF concentration in cyst fluid, but no significant correlation (P = 0.20) between cyst volume and VEGF concentration. CONCLUSION: Significantly increased VEGF concentrations were found in bloody cyst fluid and in cyst fluid of thyroid adenomatous goiter, compared with VEGF concentrations in degenerative thyroid cysts. Our results suggest that VEGF may play an important role in the pathogenesis of thyroid cyst fluid.

Typical chest pain and normal coronary angiogram: cardiac risk factor analysis versus PET for detection of microvascular disease.

UNLABELLED: Angiography of patients with typical chest pain reveals normal epicardial coronary arteries in about 20%. Coronary flow reserve (CFR) determination is an elaborate, but helpful, task, as only the evidence of microvascular disease enables appropriate therapy. We prospectively evaluated the incidence of a dysfunctional microcirculation and searched for predictive parameters of a reduced CFR. METHODS: In 79 consecutive patients (52 females, 27 males) with typical angina and a normal angiogram and 10 control subjects (6 females, 4 males), CFR was measured by 13N-ammonia rest/dipyridamole PET and correlated with clinical parameters individually and summarized as the number of risk factors (NRF) using an elaborated cardiac risk factor score. RESULTS: Sixty-five percent of patients had a reduced CFR (CFR < 2.5). CFR correlated with NRF (r = 0.55, P < 0.001), systolic blood pressure (r = 0.46, P < 0.001), interventricular septal thickness (r = 0.33, P < 0.01), and age (r = 0.25, P = 0.02). Eighty-five percent of patients with a high risk factor score (NRF > or = 5) had a reduced CFR. In contrast, 100% of our patients with a low risk factor score (NRF < 2) presented a normal CFR. In total, 55% of our patients could be allocated to either one of these groups. CONCLUSION: In about two thirds of patients, anginal pain can be explained by a reduced CFR. Risk factors have a cumulative negative effect on CFR. A clinical cardiac risk factor analysis enables estimation of individual probability of microvascular dysfunction in a significant proportion of these patients. However, CFR measurements are recommended for those with an intermediate NRF.

Calcitonin measurements for early detection of medullary thyroid carcinoma or its premalignant conditions in Hashimoto's thyroiditis.

The measurement of basal serum calcitonin (CT) in patients with evidence of Hashimoto's thyroiditis (HT) has been proposed in a recent study demonstrating an increased prevalence of elevated basal and stimulated CT. The aim of this study was to evaluate the frequency and relevance of elevated CT levels in HT. The basal sera CT were measured in 568 consecutive HT patients using a chemiluminescent immuno-assay. Whenever the serum CT was > 10 pg/ml, a pentagastrin (PG) stimulation test was performed. Two patients with abnormal/pathological PG tests were identified. Total thyroidectomy and lymph node dissection revealed for the first patient medullary thyroid carcinoma (MTC) and for the second patient C cell hyperplasia (CCH), together with papillary thyroid carcinoma. Our data showed a low prevalence of MTC and its premalignant condition CCH in HT patients; nevertheless, the patient with MTC presented lymph node metastasis. The fact that both cases presented without evidence of nodular thyroid disease highlights the persistent diagnostic dilemma of CT screening programs.

Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension.

Primary pulmonary hypertension is a fatal disease causing progressive right heart failure within 3 years after diagnosis. We describe a new concept for treatment of the disease using vasoactive intestinal peptide, a neuropeptide primarily functioning as a neurotransmitter that acts as a potent systemic and pulmonary vasodilator. Our rationale is based on the finding of a deficiency of the peptide in serum and lung tissue of patients with primary pulmonary hypertension, as evidenced by radioimmunoassay and immunohistochemistry. The relevance of this finding is underlined by an upregulation of corresponding receptor sites as shown by Northern blot analysis, Western blot analysis, and immunological techniques. Consequently, the substitution with the hormone results in substantial improvement of hemodynamic and prognostic parameters of the disease without side effects. It decreased the mean pulmonary artery pressure in our eight study patients, increased cardiac output, and mixed venous oxygen saturation. Our data provide enough proof for further investigation of vasoactive intestinal peptide and its role in primary pulmonary hypertension.