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Objective: The aim of this study was to determine the prevalence of salivary and lacrimal gland dysfunction and a second primary malignancy in patients from Taiwan with thyroid cancer after radioiodine therapy. Methods: This nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Database from 2000 to 2011. A total of 1,834 thyroid cancer patients treated with I therapy and 1,834 controls (thyroid cancer without I therapy) selected by 1:1 matching on a propensity score were enrolled. The cumulative I dose in each patient was calculated. A Cox proportional hazards model was applied to estimate the effect of radiation from the I therapy on the risk of salivary and lacrimal gland impairment as well as second primary malignancies in terms of hazard ratios (HRs) and 95 % confidence intervals (CIs). Results: In patients treated with I therapy and in controls, the incidence rates of salivary gland dysfunction were 6.76 and 1.01 per 10,000 person-years, respectively (HR 6.81, 95 % CI 0.74 - 55.3), the incidence rates of keratoconjunctivitis sicca (KCS) were 13.6 and 16.3 per 10,000 person-years, respectively (HR 0.84, 95 % CI 0.41 - 1.73), and the incidence rates of second primary malignancy were 76.7 and 62.4 per 10,000 person-years, respectively (HR 1.23, 95 % CI 0.88 - 1.72). The risk of salivary secretion impairment significantly increased with increasing administered doses (HR 14.3, 95 % CI 1.73 - 119.0). However, there was no increase in the incidence of KCS or secondary cancer in patients treated with higher doses. Conclusion: I therapy insignificantly increased the risk of salivary gland dysfunction and second primary malignancy. In patients with higher cumulative doses, an increase in the incidence of salivary gland dysfunction was observed. By contrast, we did not find an association between I treatment and KCS development. [ABSTRACT FROM AUTHOR]

Purpose: Myocardial blood flow (MBF) quantification with dynamic SPECT could lead to widespread utilization of MBF imaging in clinical practice with little cost increase over current standard SPECT myocardial perfusion imaging. This work evaluates the feasibility and operator-dependent variability of MBF and flow reserve measurements with Tc-sestamibi (MIBI) dynamic SPECT imaging using a standard dual-head SPECT camera. Methods: Twenty-eight patients underwent dipyridamole-stress and rest imaging with dynamic SPECT/CT acquisition. Quantitative images were iteratively reconstructed with all physical corrections and then myocardial and arterial blood regions of interest (ROI) were defined semi-automatically. A compartmental model was fitted to these ROI-sampled time-activity-curves, and flow-dependent MIBI extraction correction was applied to derive regional MBF values. Myocardial flow reserve (MFR) was estimated as stress/rest MBF ratio. MBF and MFR in low and high risk populations were evaluated for ability to detect disease. Images were each processed twice (≥7 days apart) by one expert and one novice operator to evaluate intra- and inter-operator variability of MBF and MFR measurement in the three coronary artery vascular territories. Results: Mean rest flow, stress flow, and MFR values were 0.83, 1.82 mL·minute·g, and 2.45, respectively. For stress/rest MFR, the inter-operator reproducibility was r = 0.86 with RPC = 1.1. Stress MBF and MFR were significantly reduced ( P < .05) in high risk (n = 9) vs low risk populations (n = 19), indicating ability to detect disease. For expert and novice operators very good intra-operator correlations of r = 0.98 and 0.95 (n = 168, P < .001) were observed for combined rest and stress regional flow values. Bland-Altman reproducibility coefficients (RPC) were 0.25 and 0.47 mL·minute·g for the expert and novice operators, respectively ( P < .001). Inter-operator correlation was r = 0.91 and Bland-Altman RPC = 0.58 mL·minute·g (n = 336). Conclusions: MBF and reserve measurements using Tc-sestamibi on a traditional, two-headed camera with fast rotation and with quantitative dynamic SPECT appears to be feasible, warranting further investigation. [ABSTRACT FROM AUTHOR]

Purpose: Conventional dual-head single photon emission computed tomography (SPECT)/CT systems capable of fast dynamic SPECT (DySPECT) imaging have a potential for flow quantitation. This study introduced a new method to quantify myocardial blood flow (MBF) and myocardial flow reserve (MFR) with DySPECT scan and evaluated the diagnostic performance of detecting coronary artery disease (CAD) compared with perfusion using invasive coronary angiography (CAG) as the reference standard. Methods: This study included 21 patients with suspected or known CAD who had received DySPECT, ECG-gated SPECT (GSPECT), and CAG (13 with ≥50 % stenosis in any vessel; non-CAD group: 8 with patent arteries or <50 % stenosis). DySPECT and GSPECT scans were performed on a widely used dual-head SPECT/CT scanner. The DySPECT imaging protocol utilized 12-min multiple back-and-forth gantry rotations during injections of Tc-sestamibi (MIBI) tracer at rest or dipyridamole-stress stages. DySPECT images were reconstructed with full physical corrections and converted to the physical unit of becquerels per milliliter. Stress MBF (SMBF), rest MBF (RMBF), and MFR were quantified by a one-tissue compartment flow model using time-activity curves derived from DySPECT images. Perfusion images were processed for GSPECT scan and interpreted to obtain summed stress score (SSS) and summed difference score (SDS). Receiver-operating characteristic (ROC) analyses were conducted to evaluate the diagnostic performance of flow and perfusion. Results: Using the criteria of ≥50 % stenosis as positive CAD, areas under the ROC curve (AUCs) of flow assessment were overall significantly greater than those of perfusion. For patient-based analysis, AUCs for MFR, SMBF, SSS, and SDS were 0.91 ± 0.07, 0.86 ± 0.09, 0.64 ± 0.12, and 0.59 ± 0.13. For vessel-based analysis, AUCs for MFR, SMBF, SSS, and SDS were 0.81 ± 0.05, 0.76 ± 0.06, 0.62 ± 0.07, and 0.56 ± 0.08, respectively. Conclusion: The preliminary data suggest that MBF quantitation with a conventional SPECT/CT system and the flow quantitation method is a clinically effective approach to enhance CAD detection. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to compare left ventricular (LV) systolic and diastolic dyssynchrony parameters measured by phase analysis on gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with those measured by speckle tracking echocardiography (STE). Materials and methods: Two patient groups were enrolled from the Chang Bing Show Chwan Memorial Hospital. The systolic group consisted of patients with reduced LV ejection fraction (LVEF) of <50 % as assessed by routine echocardiography. The diastolic group consisted of patients with normal LVEF (>50 %) and diastolic dysfunction according to routine echocardiography (E/A <1, E/E′ >8). LV systolic and diastolic dyssynchrony parameters were calculated using STE as the maximal peak-time delay between peak radial strains of two opposing LV walls and as the standard deviation of the time to peak radial strains in 6 mid-LV segments. All of the patients had gated SPECT MPI within 6 ± 11 days post STE. Phase analysis was performed on the resting gated SPECT MPI images to calculate systolic and diastolic phase standard deviation and phase histogram bandwidth as markers of LV systolic and diastolic dyssynchrony, respectively. Results: Fifty-two consecutive patients (40 men, mean age = 66 ± 13 years, LVEF = 34.4 ± 10.2 %) were enrolled in the systolic group, whereas 30 consecutive patients (15 men, mean age = 69 ± 11 years, LVEF = 72.3 ± 4.7 %, E/A all <1, E/E′ = 11.7 ± 2.2) were enrolled in the diastolic group. LV systolic and diastolic dyssynchrony parameters measured by phase analysis of gated SPECT MPI and STE were correlated well in both systolic and diastolic groups, respectively. Conclusion: Phase analysis on gated SPECT MPI showed good correlations with STE and is suitable for the assessment of LV systolic and diastolic dyssynchrony. As assessed with the phase analysis and STE techniques, the patients with severe LV systolic dysfunction had severe LV systolic dyssynchrony, but the patients with LV diastolic dysfunction were not necessarily with LV diastolic dyssynchrony, indicating that the LV diastolic dyssynchrony parameters characterized independent mechanisms of LV regional diastolic function. [ABSTRACT FROM AUTHOR]

Simple Summary: We report a local control prediction model for patients undergoing MRgFUS ablation, and provide promising guidance for clinicians to identify a suitable treatment strategy for bone metastatic lesions. We propose a few-shot learning approach to establish the quick prediction of clinical and radiographic responses. On the basis of demographic data, pre-/post-treatment immune-related cytokine change, and MRI imaging, the most suitable parameters were selected to assess potential treatment outcomes during the acute inflammatory stages within 24 h. Traditional logistic regression and few-shot learning models were compared to identify the best model on an independent test. The best predictive few-shot learning model (accuracy of 85.2%, sensitivity of 88.6%, and AUC of 0.95) was achieved by combining the clinical features with the levels of significant cytokines IL-6, IL-13, IP-10, and eotaxin. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) constitutes a noninvasive treatment strategy to ablate deep-seated bone metastases. However, limited evidence suggests that, although cytokines are influenced by thermal necrosis, there is still no cytokine threshold for clinical responses. A prediction model to approximate the postablation immune status on the basis of circulating cytokine activation is thus needed. IL-6 and IP-10, which are proinflammatory cytokines, decreased significantly during the acute phase. Wound-healing cytokines such as VEGF and PDGF increased after ablation, but the increase was not statistically significant. In this phase, IL-6, IL-13, IP-10, and eotaxin expression levels diminished the ongoing inflammatory progression in the treated sites. These cytokine changes also correlated with the response rate of primary tumor control after acute periods. The few-shot learning algorithm was applied to test the correlation between cytokine levels and local control (p = 0.036). The best-fitted model included IL-6, IL-13, IP-10, and eotaxin as cytokine parameters from the few-shot selection, and had an accuracy of 85.2%, sensitivity of 88.6%, and AUC of 0.95. The acceptable usage of this model may help predict the acute-phase prognosis of a patient with painful bone metastasis who underwent local MRgFUS. The application of machine learning in bone metastasis is equivalent or better than the current logistic regression. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the feasibility of using 4-[F]-ADAM as a brain SERT imaging agent in humans. Methods: Enrolled in the study were 19 healthy Taiwanese subjects (11 men, 8 women; age 33 ± 9 years). The PET data were semiquantitatively analyzed and expressed as specific uptake ratios (SUR) and distribution volume ratios (DVR) using the software package PMOD. The SUR and DVR of 4-[F]-ADAM in the raphe nucleus (RN), midbrain (MB), thalamus (TH), striatum (STR) and prefrontal cortex (PFC) were determined using the cerebellum (CB) as the reference region. Results: 4-[F]-ADAM bound to known SERT-rich regions in human brain. The order of the regional brain uptake was MB (RN) > TH > STR > PFC > CB. The DVR ( n = 4, t* = 60 min) in the RN, TH, STR and PFC were 3.00 ± 0.50, 2.25 ± 0.45, 2.05 ± 0.31 and 1.40 ± 0.13, respectively. The optimal time for imaging brain SERT with 4-[F]-ADAM was 120-140 min after injection. At the optimal imaging time, the SURs ( n = 15) in the MB, TH, STR, and PFC were 2.25 ± 0.20, 2.28 ± 0.20, 2.12 ± 0.18 and 1.47 ± 0.14, respectively. There were no significant differences in SERT availability between men and women ( p < 0.05). Conclusion: The results of this study showed that 4-[F]-ADAM was safe for human studies and its distribution in human brain appeared to correlate well with the known distribution of SERT in the human brain. In addition, it had high specific binding and a reasonable optimal time for imaging brain SERT in humans. Thus, 4-[F]-ADAM may be feasible for assessing the status of brain SERT in humans. [ABSTRACT FROM AUTHOR]

BACKGROUND Water ingestion elicits an osmopressor response in patients with impaired baroreflexes. In young, healthy subjects, water elicits sympathetic vasoconstriction. This study investigated the effect of water on the lower body negative pressure (LBNP)–induced vasovagal reaction and also analyzed its effect on the change of regional cerebral blood flow during LBNP. METHODS Twelve young healthy subjects underwent LBNP (40mm Hg) tolerance testing for 45 minutes or until presyncopal symptoms occurred. Subjects received either LBNP or no LBNP with or without prior water ingestion. The severity of vasovagal reaction was determined by participant self-report rating of orthostatic symptoms during the LBNP test. Changes of regional cerebral blood flow (rCBF) between LBNP and water ingestion with LBNP groups were assessed using statistical parametrical mapping analyses. RESULTS Water ingestion attenuated the severity of symptomatic scores during LBNP (P = 0.004). Water ingestion increased Total peripheral vascular resistance (P < 0.001) and attenuated the blood pressure drop (P < 0.001) at the cessation of study. LBNP decreased rCBF over the left superior prefrontal gyrus, limbic-parahippocampal gyrus, left sublobar-caudate body, and hypothalamus (P < 0.001). Water increased rCBF significantly over the right frontal lobe, including the inferior and medial prefrontal gyrus, subcallosal, and sublobar insula, during LBNP stimulation (P < 0.001). CONCLUSIONS Water ingestion strongly reduces symptomatic burden of the vasovagal reaction induced by LBNP stimulation. The cortical activation of limbic and prefrontal cortex likely indicates the involvement of osmopressor response in central autonomic cardiovascular physiology. The central cortical activation of osmopressor response might provide insight into the mechanisms by which water ingestion reduces the vasovagal reaction. [ABSTRACT FROM PUBLISHER]

Abstract: 4-[18F]F-ADAM (1a), 2-[18F]F-ADAM (2a), N-Desmethyl-4-[18F]F-ADAM (3a) and [18F]F-AFM (4a ) were synthesized in 1.7, 3.9, 2.9 and 0.6% yield (EOS), respectively, in a synthesis time of ∼120min from EOB. PET studies in rats showed that the maximum specific uptake ratios of 1a, 2a, 3a and 4a in midbrain were 3.86, 0.73, 0.35 and 2.23, respectively. Thus, in terms of radiochemical yield, specific binding and in vivo stability, 4-[18F]F-ADAM may be the most appropriate SERT imaging agent for human studies. [Copyright &y& Elsevier]

Abstract: Introduction: Serotonin transporter (SERT) has been associated with many psychiatric diseases. This study investigated the biodistribution of a serotonin transporter imaging agent, N,N-dimethyl-2-(2-amino-4-18F-fluorophenylthio)benzylamine (4-[18F]-ADAM), in nonhuman primate brain using positron emission tomography (PET). Methods: Six and four Macaca cyclopis monkeys were used to determine the transit time (i.e., time necessary to reach biodistribution equilibrium) and the reproducibility of 4-[18F]-ADAM biodistribution in the brain, respectively. The sensitivity and specificity of 4-[18F]-ADAM binding to SERT were evaluated in one monkey challenged with different doses of fluoxetine and one monkey treated with 3,4-methylendioxymethamphetamine (MDMA). Dynamic PET imaging was performed for 3 h after 4-[18F]-ADAM intravenous bolus injection. The specific uptake ratios (SURs) in the midbrain (MB), thalamus (TH), striatum (ST) and frontal cortex (FC) were calculated. Results: The distribution of 4-[18F]-ADAM reached equilibrium 120–150 min after injection. The mean SURs were 2.49±0.13 in MB, 1.59±0.17 in TH, 1.35±0.06 in ST and 0.34±0.03 in FC, and the minimum variability was shown 120–150 min after 4-[18F]-ADAM injection. Using SURs and intraclass coefficient of correlation, the test/retest variability was under 8% and above 0.8, respectively, in SERT-rich areas. Challenge with fluoxetin (0.75–2 mg) dose-dependently inhibited the SURs in various brain regions. 4-[18F]-ADAM binding was markedly reduced in the brain of an MDMA-treated monkey compared to that in brains of normal controls. Conclusion: 4-[18F]-ADAM appears to be a highly selective radioligand for imaging SERT in monkey brain. [Copyright &y& Elsevier]

Objectives. Evidence has suggested that the serotonin transporter (SERT) plays a role in the pathogenesis of alcohol dependence, anxiety and depression and that polymorphisms of the serotonin-transporter-linked promoter region (5-HTTLPR) may influence the SERT. This study evaluated the differences in SERT availability between healthy controls and alcoholic patients and the impact of 5-HTTLPR polymorphisms on SERT availability. Methods. Eleven healthy controls and 28 alcoholic patients were recruited. SERT availability was measured in vivo with single photon emission computed tomography and 123I-labelled 2-((2-((dimethyl-amino)methyl)phenyl)thio)-5-iodophenylamine in the midbrain, thalamus and striatum. Each subject was genotyped for the 5-HTTLPR polymorphism. Results. Compared to healthy controls, there was a significantly lower availability of SERT in the midbrain among patients with pure alcohol dependence (pure ALC). Of patients with anxiety, depression and alcohol dependence (ANX/DEPALC), the carriers of one LA allele showed a significantly higher availability of SERT in the striatum compared to non-LA carriers. After Bonferroni correction, these significances vanished. There were no significant differences in SERT availability between controls and ANX/DEP ALC. Conclusions. The results suggest that pure alcoholics may have lower SERT availability in the midbrain; the 5HTTLPR polymorphism may influence SERT availability in ANX/DEP ALC. These findings may serve as a springboard for future large-scale studies. [ABSTRACT FROM AUTHOR]