Two decades of SPECT/CT - the coming of age of a technology: An updated review of literature evidence.

PURPOSE: Single-photon emission computed tomography (SPECT) combined with computed tomography (CT) was introduced as a hybrid SPECT/CT imaging modality two decades ago. The main advantage of SPECT/CT is the increased specificity achieved through a more precise localization and characterization of functional findings. The improved diagnostic accuracy is also associated with greater diagnostic confidence and better inter-specialty communication. METHODS: This review presents a critical assessment of the relevant literature published so far on the role of SPECT/CT in a variety of clinical conditions. It also includes an update on the established evidence demonstrating both the advantages and limitations of this modality. CONCLUSIONS: For the majority of applications, SPECT/CT should be a routine imaging technique, fully integrated into the clinical decision-making process, including oncology, endocrinology, orthopaedics, paediatrics, and cardiology. Large-scale prospective studies are lacking, however, on the use of SPECT/CT in certain clinical domains such as neurology and lung disorders. The review also presents data on the complementary role of SPECT/CT with other imaging modalities and a comparative analysis, where available.

Voiding cystourethrography and 99MTC-MAG3 renal scintigraphy in pediatric vesicoureteral reflux: what is the role of indirect cystography?

BACKGROUND: Primary vesicoureteral reflux (VUR) is the most common urological anomaly in children. Voiding cystourethrography (VCUG) is considered the reference standard for the diagnosis of VUR. Even if it is a secure and standardized technique, it is still an invasive method, hence, the effort to find an alternative method to diagnose VUR. The aim of the study is to evaluate the diagnostic accuracy of 99mTC-MAG3 scintigraphy with indirect cystography in detecting VUR and to estimate any interobserver variability in 99mTC-MAG3 scintigraphy interpretation. METHODS: The authors retrospectively reviewed all the pediatric patients who underwent both a VCUG and a 99mTC-MAG3 renal scintigraphy at the study institution between 2012 and 2016. RESULTS: A total of 86 children (and 168 renal units) were included. MAG3 scan revealed a sensitivity of 54% and a specificity of 90% with positive predictive value of 79% and negative predictive value of 73%. Each MAG3 scintigraphy was then independently and blindly evaluated by a pediatric urologist and two nuclear physicians. After revision, the concordance between VCUG and MAG3 in reflux cases dropped from 54% to 27% (on average), and the reviewers reclassified most examinations as non-conclusive. CONCLUSIONS: 99mTC-MAG3 renal scintigraphy with indirect cystography showed low sensitivity in detecting VUR of any grade and cannot, therefore, be proposed as completely alternative to VCUG in the diagnosis of VUR. Moreover, MAG3 scintigraphy interpretation for the diagnosis of VUR has a very high interobserver variability, mostly because of the lack of a correct and complete voiding phase.

Percutaneous Lung Tumor Biopsy Under CBCT Guidance with PET-CT Fusion Imaging: Preliminary Experience.

PURPOSE: The aim of this study is to evaluate the feasibility of percutaneous lung tumor biopsy under cone beam-computed tomography (CBCT) with PET-CT imaging fusion. MATERIALS AND METHODS: Eleven patients (four women and seven men) underwent C-arm CBCT lung biopsy with PET-CT fusion imaging. A preprocedural PET-CT scan was manually fused with procedural CBCT based on anatomical landmarks; using real-time fluoroscopy, the coregistered PET-CT and CBCT images were overlaid to guide the needle trajectory. Technical success, accuracy, sensibility and specificity were evaluated. Mean total procedure time and time required for image elaboration were recorded. RESULTS: Technical success, diagnostic accuracy, sensitivity and specificity were 100%. The mean procedure time was 38 min. The average time of PET-CT/CBCT image fusion elaboration was 3.53 min for planning and 3.42 min for needle positioning check. CONCLUSION: CBCT-guided percutaneous lung biopsy with PET-CT fusion imaging is a feasible and effective procedure, with the potential to further improve diagnostic yield by targeting the most metabolically active portion of a lesion, whether it is morphologically altered or normal.

Yttrium-90 radioembolization treatment for unresectable hepatocellular carcinoma: a single-centre prognostic factors analysis.

The aim of this study was to evaluate the efficacy and the safety of Y90 radioembolization (Y90-RE) in patients with unresectable hepatocellular carcinoma (HCC) analysing our results and correlating them with independent prognostic factors for overall survival (OS) and for complications. Forty-three patients with advanced inoperable HCC including those with multiple bilobar lesions or portal vein thrombosis (PVT) treated with Y90-RE were reviewed. Treatment efficacy and safety were evaluated. Survival was calculated by the Kaplan-Meier method. Univariate analyses were performed for identifying potential prognostic factors. Radiologic response was evaluated with the modified Response Evaluation Criteria in Solid Tumours (mRECIST) criteria. Clinical toxicities were prospectively recorded. Median overall progression-free survival and OS were 27.7 and 16.8 months, respectively. Longer median OS was revealed in those without PVT (p = 0.0241) and those whose pre-treatment haemoglobin values was higher (p = 0.0471). According with mRECIST criteria, we observed a disease control rate of 69.2 and 61.9% at 3- and 6-month follow-up, respectively. Complications developed in 28 patients (65.1%), among which grade 2-3 events were reported in 17 patients. We noted that activity administered dose presented a correlation with intra-procedural toxicity (p = 0.039259) while common hepatic artery use as release site was associated with a most frequent presentation of remote adverse events. Y90-RE is an alternative treatment with a promising outcome for poor-risk advanced inoperable HCC. PVT and pre-treatment haemoglobin values can be predictors of efficacy. Activity administered dose and arterial release site can be predictors of safety.

Prevalence of simple nodular goiter and Hashimoto's thyroiditis in current, previous, and never smokers in a geographical area with mild iodine deficiency.

Simple nodular goiter and Hashimoto's thyroiditis are 2 frequent nonmalignant thyroid diseases. Tobacco smoking has detrimental effects on the endocrine system and in particular on thyroid function and morphology. The objective of this cross-sectional study, involving 1800 Caucasian adults from a geographical area with mild iodine deficiency, was to evaluate the relationship between tobacco smoking, smoking cessation, and the prevalence of simple nodular goiter and Hashimoto's thyroiditis. Thyroid status was evaluated by ultrasonic exploration of the neck, measurement of FT3, FT4, TSH, antibodies against thyroid peroxidase and thyroglobulin, and urinary iodine excretion. The fine-needle aspiration biopsy of significant nodules was also performed. Smoking habits were evaluated by a specific questionnaire and the calculation of number of pack years. Both current and previous smokers showed an increased risk of simple nodular goiter compared to never smokers after adjustment for potential confounders and known goitrogen factors. Interestingly, the simple nodular goiter risk was similar for never smokers and for previous smokers declaring a time since cessation of smoking for more than 69 months. Smoking habit was not associated to an increased risk of Hashimoto's thyroiditis.Smoking appears to be an independent risk factor for simple nodular goiter but not for Hashimoto's thyroiditis in an area with mild iodine deficiency. A prolonged withdrawal of smoking dramatically reduces the risk of simple nodular goiter occurrence.

Renal radionuclide imaging, an evergreen forty years old.

Urinary tract congenital abnormalities (UCA) and febrile infections (UTI) are, respectively, 2 of the commonest congenital and acquired health problems in childhood. In both, radionuclide imaging still represent a cornerstone of diagnostic imaging, although the involved techniques are more or less the same from the early '80 s. During the last 2 decades, published papers focused on a deep revision about the optimal use and usefulness of such imaging tools in affected children, with the aim of reducing invasiveness, radiation burden and costs without losing efficacy. This approach leads to different results. In UCA, no consensus for a diagnostic algorithm was up to now reached, whilst, about febrile UTIs, guidelines were published in 2007 by the UK's National Institute for Clinical Excellence (NICE) and by the European Society of Paediatric Radiology (ESPR), in 2011 by the American Academy of Paediatrics (AAP), and in 2012 by the Italian Society of Paediatric Nephrology (SINP). Nevertheless, new data continuously arise and the scientific debate always revives. Every imaging tool now available has its own strengths and weaknesses, and so all published guidelines. All this body of knowledge must be critically analysed for obtaining a complete, up-to-date and flexible overview about these "always hot" topics.

Hyperleptinemia is associated with hypertension, systemic inflammation and insulin resistance in overweight but not in normal weight men.

BACKGROUND AND AIM: High leptin (LPT) is associated with high blood pressure (BP), insulin resistance and systemic inflammation but also excess body weight and adiposity. To disentangle these multiple relations, we analyzed BP, HOMA and circulating C-reactive protein concentration (hs-CRP) in white male adults with different LPT levels but similar age, body mass index (BMI) and body fat distribution. The novel aspect is the different statistical approach used to investigate the relation between LPT and the other alterations present in obesity. METHODS AND RESULTS: 972 Olivetti Heart Study participants were stratified according to the median LPT distribution (2.97 ng/ml) into low LPT (l-LPT) and high LPT (h-LPT). The two groups were then carefully matched for age and BMI. We identified two groups of 207 h-LPT and 207 l-LPT individuals with overlapping age, BMI and waist/hip ratio. The two groups had different BP (132.9 ± 16.2/85.7 ± 9.0 vs 128.7 ± 18.2/82.8 ± 9.8 mmHg, p = 0.014 for SBP and p = 0.002 for DBP) and prevalence of hypertension (57% vs 43%, p = 0.027). Upon separate evaluation of untreated individuals with BMI < 25 or BMI ≥ 25, within the latter subgroup h-LPT compared with l-LPT participants (n = 133 each group) had higher BP (p = 0.0001), HOMA index (p = 0.013), hs-CRP (p = 0.002) and heart rate (p = 0.008) despite similar age and BMI. By contrast, within the normal weight subgroup, h-LPT individuals did not differ from l-LPT (n = 37 each) for any of these variables. CONCLUSIONS: High LPT is associated with higher BP, HR, hs-CRP and HOMA index independently of BMI and fat distribution but only among overweight individuals.

High-circulating leptin levels are associated with greater risk of hypertension in men independently of body mass and insulin resistance: results of an eight-year follow-up study.

BACKGROUND: We previously reported a significant association between plasma leptin (LPT) concentration and blood pressure (BP), which was partly independent of serum insulin levels and insulin resistance. The aims of this study were to detect whether serum LPT levels predict the development of hypertension (HPT) in the 8-yr follow-up investigation of a sample of an adult male population (the Olivetti Heart Study), and to evaluate the role of body mass index (BMI) and insulin resistance in this putative association. PATIENTS AND METHODS: The study population was made up of 489 untreated normotensive subjects examined in 1994-1995 (age: 50.1 +/- 6.7 yr; BMI: 26.3 +/- 2.8 kg/m(2); BP: 120 +/- 10/78 +/- 6 mm Hg; and homeostatic model assessment index: 2.1 +/- 1.6). RESULTS: The HPT incidence over 8 yr was 35%. The participants with incident HPT had similar age but higher BMI (P < 0.001), serum LPT (P < 0.001), and BP (P < 0.01) at baseline. One sd positive difference in baseline serum LPT log was associated at univariate analysis with a 49% higher rate of HPT [95% confidence interval (CI) 22-83; P < 0.001]). In three different models of multivariable logistical regression analysis, LPT was respectively associated with a 41% greater risk to develop HPT (95% CI 15-74; P < 0.001) upon adjustment for age and baseline BP, with a 48% (95% CI 20-81) greater risk when adding the homeostatic assessment model index to the model, and with 33% greater risk (95% CI 6-67; P < 0.02) upon adjustment for BMI. CONCLUSIONS: In this sample of originally normotensive men, circulating LPT level was a significant predictor of the risk to develop HPT over 8 yr, independently of BMI and insulin resistance.

Changes in autonomic modulation to the heart and intracellular catecholamines. A longitudinal study in differentiated thyroid carcinoma during short-term hypothyroidism and thyroid hormone replacement.

BACKGROUND: The effects of thyroid deprivation on the autonomic modulation to the heart remain controversial. METHODS: In this study in patients followed for thyroid carcinoma, we investigated (1) heart rate variability parameters and the baroreflex gain and (2) intracellular catecholamine levels in circulating lymphocytes during short-term hypothyroidism (phase 1) and after reinstitution of TSH-suppressive thyroid hormone replacement (phase 2). RESULTS: The RR interval value (p < 0.01) and systolic blood pressure (p < 0.05) were higher in phase 1 than in phase 2. The low-frequency/high-frequency (LF/HF) ratio was significantly lower in the hypothyroid state (p < 0.05), with a higher HF component (p < 0.05). After adjusting for mean RR interval in the regression model, the difference between the power of RR interval oscillations calculated in the two states was greater for the LF band (p = 0.005) and it was borderline significant for the HF band (p = 0.052). The baroreflex gain alpha(LF) index was similar in the two phases. The stimulus-induced cellular production of norepinephrine and epinephrine in peripheral blood mononuclear cells was significantly higher in phase 2. CONCLUSION: The neurally-mediated influences on the sinus node and the study of intracellular catecholamine production suggest a reduced sympathoexcitation in hypothyroidism compared with the treatment phase. The early increase in blood pressure observed after thyroid hormone withdrawal is not due to impaired sensitivity of the baroreflex arc.

Thyroid hormone and thyrotropin regulate intracellular free calcium concentrations in human polymorphonuclear leukocytes: in vivo and in vitro studies.

Intracellular free calcium concentrations (Ca++i) were studied in polymorphonuclear leukocytes (PMNs) from 13 athyreotic patients who had been previously treated by total thyroidectomy and radioiodine therapy for differentiated thyroid carcinoma, and from age- and sex-matched euthyroid healthy controls. Patients were studied twice, when hypothyroid (visit 1) and after restoration of euthyroidism by L-T4 TSH-suppressive therapy (visit 2). PMNs from patients at visit 1 had significantly lower resting (Ca++)i levels compared to both visit 2 and controls. Values at visit 2 did not differ from those of the controls. Stimulus-induced (Ca++)i rise was also significantly blunted at visit 1 and normalized at visit 2, possibly through a differential contribution of distinct intracellular Ca++ stores, as suggested by the response pattern to the chemotactic agent, N-formyl-Met-Leu-Phe (fMLP), to the selective SERCA pump inhibitor, thapsigargine, and to the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP). In vitro treatment of PMNs from healthy subjects with high TSH concentrations impaired intracellular Ca++ store function. Both resting (Ca++)i levels and fMLP-induced (Ca++)i rise increased in the presence either of low-concentration TSH or of T4, but effects of TSH and T4 were not additive. T3, rT3, and TRIAC had no effect. In conclusion, this study provides evidence for a direct relationship between thyroid status and (Ca++)i homeostasis in human PMNs, mainly related to direct actions of TSH and T4 on these cells.

[Radioiodine treatment of hyperthyroidism using a simplified dosimetric approach. Clinical results]. / Terapia radiometabolica dell'ipertiroidismo con approccio dosimetrico semplificato. Risultati clinici.

PURPOSE: To evaluate the clinical effectiveness of a simplified dosimetric approach to the iodine-131 treatment of hyperthyroidism due to Graves' disease or uninodular and multinodular toxic goiter. MATERIAL AND METHODS: We enrolled 189 patients with biochemically confirmed hyperthyroidism and performed thyroid ultrasonography and scintigraphy obtaining the diagnosis of Graves' disease in 43 patients, uninodular toxic goiter in 57 patients and multinodular toxic goiter in 89 patients. In 28 patients we found cold thyroid nodules and performed fine-needle aspiration with negative cytology for thyroid malignancy in all cases. Antithyroid drugs were stopped 5 days till radioiodine administration and, if necessary, restored 15 days after the treatment. Radioiodine uptake test was performed in all patients and therapeutic activity calculated to obtain a minimal activity of 185 MBq in the thyroid 24 hours after administration. The minimal activity was adjusted based on clinical, biochemical and imaging data to obtain a maximal activity of 370 MBq after 24 hours. RESULTS: Biochemical and clinical tests were scheduled at 3 and 12 months posttreatment and thyroxine treatment was started when hypothyroidism occurred. In Graves' disease patients a mean activity of 370 MBq (distribution 259-555 MBq) was administered. Three months after treatment and at least 15 days after methimazole discontinuation 32 of 43 (74%) patients were hypothyroid, 5 of 43 (11%) euthyroid and 6 of 43 (15%) hyperthyroid. Three of the latter were immediately submitted to a new radioiodine administration while 32 hypothyroid patients received thyroxine treatment. One year after the radioiodine treatment no patient had hyperthyroidism; 38 of 43 (89%) were on a replacement treatment while 5 (11%) remained euthyroid. In uni- and multinodular toxic goiter a mean activity of 444 MBq (distribution 259-555 MBq) was administered. Three months posttreatment 134 of 146 (92%) patients were euthyroid and 12 of 146 (8%) patients hyperthyroid. Two patients were immediately submitted to a new radioiodine administration. One year posttreatment 142 of 146 (97%) patients were euthyroid while only 4 of 146 (3%) patients showed TSH levels above the normal range. Only 2 of them required thyroxine treatment. CONCLUSIONS: The simplified dosimetric method illustrated in our paper is very effective in clinical practice because it permits to avoid resorting to sophisticated but also imprecise quantitative methods. Hypothyroidism should not be considered as a major collateral effect of radioiodine treatment, particularly in Graves' disease. In fact, the pathogenesis of the disease requires an ablative treatment with both surgery and radioidine treatment and the control of hyperthyroidism and the prevention of relapse are the major clinical targets. Vice versa, hypothyroidism was very uncommon in uni- and multinodular toxic goiter when our dosimetric approach was applied.

Uptake of In-111 pentetreotide by normally functioning nodular goiters.

After the intravenous administration of a radiolabeled somatostatin analogue (octreotide), normal thyroid and neoplastic and nonneoplastic thyroid lesions can be visualized. The authors present the cases of two patients who underwent somatostatin receptor scintigraphy (SSRS) using In-111 pentetreotide: one for the study of suspected paraneoplastic ACTH hypersecretion, and the other for a restaging of breast carcinoma with neuroendocrine features. In both patients, SSRS revealed increased uptake in the thyroid, corresponding to "cold" nodules on Tc-99m pertechnetate imaging. Cytologic and histologic examinations showed the typical features of thyroid goiters without lymphocytic infiltration.

The clinical use of 99m-Tc-labeled WBC scintigraphy in critically ill surgical and trauma patients with occult sepsis.

OBJECTIVE: To evaluate the clinical use of radionuclide-labeled white blood cell scintigraphy in the detection of focal sepsis. DESIGN: Prospective clinical study. SETTING: A medical/surgical 12-bed intensive care unit (ICU) in a university hospital. PATIENTS: 26 trauma and surgical patients affected by sepsis of unknown origin were studied. MEASUREMENTS AND RESULTS: After the usual diagnostic approach, patients were submitted to a total body scan by using the patient's leukocytes labeled with technetium-99m (99m-Tc) HMPAO; three scintigraphy were performed within 20 h of tracer injection; the result of scan was completed with all clinical and instrumental data, including ultrasound (US) arnd computed tomography (CT), and the diagnostic efficacy was demonstrated for each patient on discharge from the ICU. The scan was able to detect 20 sites of infection; it was possible to rule out 11 suspected sites; only in two cases was the result considered to be false positive or false negative; in two cases the result was considered to be uncertain. These results show the high sensitivity (95%), specificity (91%) and accuracy (94%) of the method. CONCLUSIONS: In ICU patients with sepsis, nuclear medicine can provide additional data, as the injection of radionuclide-labeled white blood cells (WBCs) allows the imaging of sites of infection. Analysis of our results suggests that scintigraphy with 99m-Tc-labeled WBCs can be considered a useful tool in the detection of the source of infection.

TSH circadian secretions in aged men and effect of phosphatidylserine treatment.

In 20 euthyroid aged men (from 65 to 85 years of age) no significant circadian periodicity of thyrotropin (TSH) secretion has been shown by the population mean cosinor method. At the end of a period of 30 days of hospitalization the cosinor evaluation of TSH secretion showed a restored highly significant (p less than 0.001) circadian rhythmicity in phosphatidylserine (PS) (400 mg/daily) treated group (10 aged subjects). By contrast, hospitalization seems to further deteriorate the periodicity of the hormone secretion in 10 placebo-treated subjects.

Cluster headache in the male: sex steroid pattern and gonadotropic response to luteinizing hormone releasing hormone.

Serum testosterone, dihydrotestosterone, delta 4-androstendione and 17 beta-estradiol, sex hormone binding globulin (SHBG) and gonadotropic response to luteinizing hormone releasing hormone (LHRH) were studied in 34 male subjects with episodic or chronic cluster headache (CH). The sex steroid free fractions and those bound to SHBG and albumin were determined by a simulatory computerized method based on the mass action law. Individual steroid values were dispersed over a wide range in CH patients. Total, free and carrier protein-bound testosterone levels were significantly diminished only in chronic CH, where luteinizing hormone (LH) peak values after intravenous administration of LHRH were also decreased. Basal and peak follicle stimulating hormone (FSH) levels were significantly increased in episodic and in chronic CH groups, in comparison to healthy controls.

Thyrotropin and prolactin responses to different doses of thyrotropin-releasing hormone in depression.

The effects of low doses of thyrotropin-releasing hormone (TRH, 50 and 200 micrograms) on thyrotropin (TSH) and prolactin levels have been studied in depressed women and compared with the depressive condition and with the results of the dexamethasone suppression test (DST). TRH administration elicited blunted hormonal responses that were not correlated either with the age of the patients or with DST results. Different effects were observed in subgroups of depressive patients classified according to DSM III and ICD. No correlation was found between hormone responses and the scores of Hamilton Rating Scale and Montgomery Depression Scale. The effects of 50 micrograms on TSH were significant and inversely correlated with Anxiety Rating Scale scores. No dose-response effect was apparent of prolactin and TSH in depressed patients, suggesting an impaired function of pituitary TRH receptors.

Thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone in common migraine.

Intravenous administration of 50 micrograms or 200 micrograms thyrotropin-releasing hormone (TRH) to men with common migraine elicited blunted prolactin (PRL) responses, when compared with healthy controls. The thyroid-stimulating hormone (TSH) response was enhanced after 50 micrograms TRH in the migraineurs, but not after 200 micrograms. The physiologic TSH dose-response relationship was abolished in migraine sufferers. The data may be interpreted in the light of dopaminergic and noradrenergic supersensitivity, for PRL and TSH, respectively. The TSH response in migraine differs from the one that occurs in depression.