Association between myocardial ischemia and plaque characteristics in chronic total occlusion.

BACKGROUND: Myocardial ischemia varies in chronic total occlusion (CTO) despite the occluded artery. We analyzed whether it is associated with the plaque characteristics of the occluded segment. METHODS: We retrospectively enrolled 100 patients with CTO who underwent myocardial perfusion single-photon emission computed tomography (SPECT) and coronary computed tomography angiography (CCTA) within 2 months. CTO-related ischemia was classified as moderate to severe (summed difference score [SDS] of the CTO territory ≥ 5) or mild or none (SDS < 5) on SPECT. Using CCTA, the atherosclerotic plaques of the occluded segment were subdivided into low-density (- 100-30 HU), intermediate-density (31-350 HU), and high-density (351-1000 HU) plaques. The plaque composition was compared according to the severity of CTO-related ischemia. RESULTS: Moderate-to-severe CTO-related ischemia (n = 23) showed significantly higher proportion of intermediate-density plaques (72.4% vs. 64.0%), intermediate/low-density (7.10 vs. 3.65) and intermediate-to-high/low-density (7.78 vs. 3.80) plaque ratios, frequent shorter occlusion (30% vs. 6%), and lower volume (26.5 mm3 vs. 58.8 mm3) and proportion (11.4% vs. 20.8%) of low-density plaques. Multivariable analysis revealed significant associations between higher proportion of intermediate-density plaques and moderate-to-severe CTO-related ischemia, independent of occlusion length. CONCLUSION: Higher proportion of intermediate-density plaques in the occluded segment was associated with the moderate-to-severe CTO-related ischemia.

Incidence rate and factors associated with the development of secondary cancers after radioiodine therapy in differentiated thyroid cancer: a multicenter retrospective study.

PURPOSE: The objective of this study was to estimate the incidence of secondary cancers and the factors associated with their development among patients who underwent radioiodine therapy (RIT) with differentiated thyroid cancer. METHODS: We retrospectively collected medical records for patients who underwent first RIT between January 1, 2000, and December 31, 2005, from seven tertiary hospitals in South Korea after total thyroidectomy for differentiated thyroid cancer. Cancer incidence and calculated standardized rate ratio were compared with Korean cancer incidence data. The association between the development of secondary cancers and various parameters was analyzed by Cox-proportional hazard regression. RESULTS: A total of 3106 patients were included in this study. Mean age at the time of diagnosis of thyroid cancer was 45.7 ± 13.3 years old, and 2669 (85.9%) patients were female. The follow-up period was 11.9 ± 4.6 (range, 1.2-19.6) years. A total of 183 secondary cancers, which included 162 solid and 21 hematologic cancers, occurred in 173 patients (5.6%). There was no significant difference between solid cancer incidence in our study population who underwent RIT and the overall Korean population, but the incidence of hematologic cancers and total cancer in our study was significantly higher compared with that of the Korean population. A multivariate analysis identified independent prognostic factors for the development of secondary cancer including age at 1st RIT, male, and total cumulative dose over 200 mCi. CONCLUSION: We need to assess the risk benefit for patients who receive over 200 mCi of a total cumulative dose.

STAT3 phosphorylation inhibition for treating inflammation and new bone formation in ankylosing spondylitis.

OBJECTIVE: AS is a rheumatic disease characterized by chronic inflammation and bony ankylosis. This study was to evaluate whether a signal transducer and activator of transcription 3 phosphorylation inhibitor (stat3-p Inh) could treat both chronic inflammation and bone formation in AS. METHODS: Primary AS osteoprogenitor cells and spinal entheseal cells were examined for osteogenic differentiation. SF mononuclear cells (SFMCs) and lamina propria mononuclear cells (LPMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analysed using flow cytometry and ELISA. Female SKG mice were treated with stat3-p Inh, IL-17A blocker or vehicle. Inflammation and new bone formation were evaluated using immunohistochemistry, PET and micro-CT. RESULTS: In the SKG mouse model, stat3-p Inh significantly suppressed arthritis, enthesitis, spondylitis and ileitis. In experiments culturing SFMCs and LPMCs, the frequencies of IFN-γ-, IL-17A- and TNF-α-producing cells were significantly decreased after stat3-p Inh treatment. When comparing current treatments for AS, stat3-p Inh showed a comparable suppression effect on osteogenesis to Janus kinase inhibitor or IL-17A blocker in AS-osteoprogenitor cells. Stat3-p Inh suppressed differentiation and mineralization of AS-osteoprogenitor cells and entheseal cells toward osteoblasts. Micro-CT analysis of hind paws revealed less new bone formation in stat3-p Inh-treated mice than vehicle-treated mice (P = 0.005). Hind paw and spinal new bone formation were similar between stat3-p Inh- and anti-IL-17A-treated SKG mice (P = 0.874 and P = 0.117, respectively). CONCLUSION: Stat-3p inhibition is a promising treatment for both inflammation and new bone formation in AS.

Association between FDG uptake in the right ventricular myocardium and cancer therapy-induced cardiotoxicity.

BACKGROUND: The aim of this study was to investigate changes in myocardial uptake evaluated by oncologic 18F-fluorodeoxyglucose (FDG) PET/CT scans and to determine the relationship between myocardial FDG uptake and cancer therapy-induced cardiotoxicity in breast cancer patients who underwent anthracycline or trastuzumab. METHODS: We reviewed 121 consecutive patients who underwent oncologic FDG PET/CT and echocardiography at baseline and post-therapy with anthracyclines or trastuzumab for breast cancer. Grade in LV wall, uptake pattern in LV wall, and the presence of RV wall uptake were assessed by visual analysis, and the mean SUV in the LV and RV walls and the change of SUV (ΔSUV) between baseline and post-therapy PET/CT were measured by quantitative analysis. Multiple logistic regression analyses were performed to evaluate the association between PET parameters and cardiotoxicity. RESULTS: Fifteen patients (12%) showed cardiotoxicity after therapy. The cardiotoxic group tended to show more diffuse LV uptake, higher SUV, and ΔSUV of RV wall than the non-cardiotoxic group following therapy with anthracyclines or trastuzumab. Logistic regression analysis showed that the presence of RV wall uptake, SUV of RV wall (> 1.8), and ΔSUV of RV wall (> 0.4) were significantly associated with cardiotoxicity after controlling for age, radiotherapy, and treatment. CONCLUSIONS: The presence of RV wall uptake and the increase of SUV of RV wall on post-therapy PET/CT were associated with cardiotoxicity in breast cancer patients who underwent anthracycline or trastuzumab. Oncologic FDG PET/CT scans can provide information regarding cancer therapy-induced cardiotoxicity as well as tumor response.

Prediction of coronary artery calcium progression by FDG uptake of large arteries in asymptomatic individuals.

PURPOSE: The purpose of this study is to evaluate whether fluorodeoxyglucose (FDG) uptake of the large arteries can predict coronary artery calcium (CAC) progression in asymptomatic individuals. METHODS: Ninety-six asymptomatic individuals who underwent FDG positron emission tomography (PET) and CAC scoring on the same day for health screening and follow-up CAC scoring ≥1 year after baseline studies (mean 4.3 years) were included. Vascular FDG uptake was measured and corrected for blood pool activity to obtain peak and average target-to-blood pool ratios (TBRpeak and TBRavg, respectively) for the carotid arteries, and ascending and abdominal aorta. CAC scores at baseline and follow-up of each individual were measured and absolute CAC change (ΔCAC), annual CAC change (ΔCAC/year), and annual CAC change rate (ΔCAC%/year) were calculated. CAC progression was defined as ΔCAC >0 for individuals with negative baseline CAC; ΔCAC/year ≥10 for those with baseline CAC of 0

Clinical values of left ventricular mechanical dyssynchrony assessment by gated myocardial perfusion SPECT in patients with acute myocardial infarction and multivessel disease.

PURPOSE: The aim of this study was to evaluate the prognostic value of additional evaluation of left ventricular mechanical dyssynchrony (LVMD) by gated myocardial perfusion single-photon emission computed tomography (GMPS) in patients with acute myocardial infarction (MI) and multivessel disease. METHODS: One hundred and nine acute MI patients with >50 % stenosis in at least one non-culprit artery who underwent GMPS within 2 weeks were enrolled. All patients underwent successful revascularization of the culprit arteries. Those with previous MI, atrial fibrillation, or frequent ventricular premature complexes, cardiac devices, significant patient motion, or procedure-related events were excluded. Phase standard deviation (PSD) and phase histogram bandwidth (PBW) were measured for assessment of LVMD. Patients were followed up for a median of 26 months after index MI, for composite major adverse cardiac events (MACE), which consisted with all-cause death, unplanned hospitalization due to heart failure and severe ventricular arrhythmias (sustained ventricular tachycardia or ventricular fibrillation). Independent predictors of MACE were evaluated. RESULTS: MACE occurred in 22 patients (20 %). Stress PSD (53.3 ± 17.3° vs. 35.3 ± 18.9°; p <0.001), stress PBW (147.6 ± 54.6° vs. 96.8 ± 59.2°; p = 0.001) and resting PBW (126.8 ± 37.5° vs. 96.6 ± 48.9°; p = 0.001) were significantly higher in patients with MACE compared to those without. Multivariate analysis revealed that stress PSD ≥45.5° and stress PBW ≥126.0° were predictive of MACE, as well as suboptimal non-culprit artery revascularization (SNR) and renin-angiotensin system (RAS) blockade medication. Higher stress PSD and stress PBW were associated with poorer prognosis both in patients with and without SNR, and those with RAS blockade medication, but not in those without RAS blockade medication. CONCLUSIONS: LVMD measured by GMPS showed added prognostic value in acute MI with multivessel disease. GMPS could serve as a comprehensive evaluation imaging tool in patients with acute MI and multivessel disease.

18F-FDG PET/CT imaging factors that predict ischaemic stroke in cancer patients.

PURPOSE: 18F-FDG PET/CT can acquire both anatomical and functional images in a single session. We investigated which factors of 18F-FDG PET/CT imaging have potential as biomarkers for an increased risk of ischaemic stroke in cancer patients. METHODS: From among cancer patients presenting with various neurological symptoms and hemiparesis, 134 were selected as eligible for this retrospective analysis. A new infarct lesion on brain MRI within 1 year of FDG PET/CT defined future ischaemic stroke. The target-to-background ratio (TBR) of each arterial segment was used to define arterial inflammation on PET imaging. Abdominal obesity was defined in terms of the area and proportion of visceral adipose tissue (VAT), subcutaneous adipose tissue and total adipose tissue (TAT) on a single CT slice at the umbilical level. RESULTS: Ischaemic stroke confirmed by MRI occurred in 30 patients. Patients with stroke had higher TBRs in the carotid arteries and abdominal aorta (P < 0.001) and a higher VAT proportion (P = 0.021) and TAT proportion (P = 0.041) than patients without stroke. Multiple logistic regression analysis showed that TBRs of the carotid arteries and abdominal aorta, VAT and TAT proportions, and the presence of a metabolically active tumour were significantly associated with future ischaemic stroke. Combining PET and CT variables improved the power for predicting future ischaemic stroke. CONCLUSION: Our findings suggest that arterial FDG uptake and hypermetabolic malignancy on PET and the VAT proportion on CT could be independent predictors of future ischaemic stroke in patients with cancer and could identify those patients who would benefit from medical treatment.

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker, in a porcine model of acute myocardial infarction.

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.

Clinical implication of F-18 FDG PET/CT in patients with secondary hemophagocytic lymphohistiocytosis.

The contribution that F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG) PET/CT makes to the diagnosis of malignancy in patients with hemophagocytic lymphohistiocytosis (HLH) is still uncertain. The aim of this study was to evaluate the diagnostic performance of F-18 FDG PET/CT for the detection of underlying malignancy, to investigate the correlation between PET and laboratory parameters, and to identify prognosis-related factors in patients with secondary HLH. We enrolled 14 patients who were diagnosed with HLH and referred for F-18 FDG PET/CT to exclude malignancy. The diagnostic performance of F-18 FDG PET/CT for malignancy detection was assessed. The correlations between PET and laboratory parameters were determined. The prognostic significance of the following factors was evaluated: PET and laboratory parameters, age in years, presence of underlying malignancy, and fever and splenomegaly. Six of the 14 patients had malignancies (four with lymphoma, one with multiple myeloma, and one with colonic malignancy). Sensitivity, specificity, and diagnostic accuracy of F-18 FDG PET/CT for malignancy detection were 83, 62.5, and 71.4 %, respectively. F-18 FDG uptake in the bone marrow and spleen was positively correlated with neutrophil count and C-reactive protein. All of the PET parameters, but none of the clinical or laboratory parameters, were significantly associated with patient outcome, as determined by univariate analysis. Given the small sample size, F-18 FDG PET/CT was useful for detecting underlying malignancy, and PET parameters correlated with laboratory parameters that reflected inflammatory status. F-18 FDG PET/CT might provide prognostic information for the management of patients with secondary HLH.

Applying Pix2pix to Translate Hyperemia in Blood Pool Image into Corresponding Increased Bone Uptake in Delayed Image in Three-Phase Bone Scintigraphy.

Purpose: Delayed images may not be acquired due to severe pain, drowsiness, or worsening vital signs while waiting after blood pool imaging in three-phase bone scintigraphy. If the hyperemia in the blood pool image contains information from which increased uptake on the delayed images can be inferred, the generative adversarial network (GAN) can generate the increased uptake from the hyperemia. We attempted to apply pix2pix, a type of conditional GAN, to transform hyperemia into increased bone uptake. Methods: We enrolled 1464 patients who underwent three-phase bone scintigraphy for inflammatory arthritis, osteomyelitis, complex regional pain syndrome (CRPS), cellulitis, and recent bone injury. Blood pool images were acquired 10 min after intravenous injection of Tc-99 m hydroxymethylene diphosphonate, and delayed bone images were obtained after 3 h. The model was based on the open-source code of the pix2pix model with perceptual loss. Increased uptake in the delayed images generated by the model was evaluated using lesion-based analysis by a nuclear radiologist in areas consistent with hyperemia in the blood pool images. Results: The model showed sensitivities of 77.8% and 87.5% for inflammatory arthritis and CRPS, respectively. In osteomyelitis and cellulitis, their sensitivities of about 44% were observed. However, in cases of recent bone injury, the sensitivity was only 6.3% in areas consistent with focal hyperemia. Conclusion: The model based on pix2pix generated increased uptake in delayed images matching the hyperemia in the blood pool image in inflammatory arthritis and CRPS.

Tc-99m DMSA SPECT for Follow-Up of Non-Operative Treatments in Renal Injuries: A Prospective Single-Center Study.

OBJECTIVE: The assessment of cortical integrity following renal injuries with planar Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy depends on measuring relatively decreased cortical uptake (i.e., split renal function [SRF]). We analyzed the additive values of the volumetric and quantitative analyses of the residual cortical integrity using single-photon emission computed tomography (SPECT) compared to the planar scintigraphy. MATERIALS AND METHODS: This prospective study included 47 patients (male:female, 32:15; age, 47 ± 22 years) who had non-operatively managed renal injuries and underwent DMSA planar and SPECT imaging 3-6 months after the index injury. In addition to planar SRF, SPECT SRF, cortical volume, and absolute cortical uptake were measured for the injured kidney and both kidneys together. The correlations of planar SRF with SPECT SRF and those of SRF with volumetric/quantitative parameters obtained with SPECT were analyzed. The association of SPECT parameters with renal function, grades of renal injuries, and the risk of renal failure was also analyzed. RESULTS: SPECT SRF was significantly lower than planar SRF, with particularly higher biases in severe renal injuries. Planar and SPECT SRF (dichotomized with a cutoff of 45%) showed 19%-36% of discrepancies with volumetric and quantitative DMSA indices (when dichotomized as either high or low). Absolute cortical uptake of the injured kidney best correlated with glomerular filtration rate (GFR) at follow-up (ρ = 0.687, P < 0.001) with significant stepwise decreases by GFR strata (90 and 60 mL/min/1.73 m²). Total renal cortical uptake was significantly lower in patients with moderate-to-high risk of renal failure than those with low risk. However, SRF did not reflect GFR decrease below 60 mL/min/1.73 m² or the risk of renal failure, regardless of planar or SPECT (count- or volume-based SRF) imaging. CONCLUSION: Quantitative measurements of renal cortical integrity assessed with DMSA SPECT can provide more clinically relevant and comprehensive information than planar imaging or SRF alone.

Whole-body metabolic tumour volume of 18F-FDG PET/CT improves the prediction of prognosis in small cell lung cancer.

PURPOSE: We investigated whether the whole-body metabolic tumour volume (WBMTV) measured by (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) can improve the prediction of prognosis in patients with small cell lung cancer (SCLC). METHODS: We reviewed 106 consecutive patients (mean age 67 years, range 42-89 years, limited stage 45 patients, extensive stage 61 patients) with pathologically proven SCLC who underwent pretreatment FDG PET/CT. WBMTV and maximum standardized uptake value (SUV(max)) were measured in all malignant lesions. The Cox proportional hazards model was used with age, sex, performance status, lactate dehydrogenase (LDH), treatment, stage, SUV(max) and WBMTV to predict overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed using WBMTV combined with conventional staging and tumour node metastasis (TNM) staging. RESULTS: The uni- and multivariate analyses showed that both stage and WBMTV were independent prognostic factors for death and progression. Patients with high WBMTV were associated with poor prognosis compared with patients with low WBMTV [hazard ratio = 2.11 (95% confidence interval 1.31-3.39) for death (p = 0.002) and 1.80 (95% confidence interval 1.16-2.80) for progression (p = 0.009)]. Incorporation of conventional staging and WBMTV could classify four subgroups with different prognoses (log-rank test, p < 0.001). Incorporation of TNM staging and WBMTV could classify six subgroups with different prognoses (log-rank test, p < 0.001). CONCLUSION: WBMTV is an independent predictor for progression and death in patients with SCLC. Incorporation of WBMTV with TNM staging can provide a more detailed prediction of prognosis than WBMTV with conventional staging as well as tumour staging alone.

Evaluation of Non-infarct-Related Arteries Using C-11 Acetate PET in STEMI With Multivessel Disease.

BACKGROUND: We analyzed whether C-11 acetate positron emission tomography (PET) can be used for the evaluation of non-infarct-related artery (NIRA) in patients with ST-elevation myocardial infarction (STEMI) and multivessel disease. METHODS: We prospectively enrolled 31 patients with STEMI and at least one NIRA stenosis (diameter stenosis [DS] ≥ 50%). C-11 acetate PET was performed after successful revascularization for the infarct-related artery (IRA). Myocardial blood flow (MBF) and oxidative metabolism (kmono) were measured and compared between NIRA vs. IRA, stenotic (DS ≥ 50%) vs. non-stenotic (DS < 50%) NIRAs, and NIRAs with significant stenosis (DS ≥ 70% or fractional flow reserve [FFR] ≤ 0.80) vs. those without (neither DS ≥ 70% nor FFR ≤ 0.80). The correlations between PET and angiographic parameters were also analyzed. RESULTS: MBF and kmono were significantly higher in NIRAs than those in IRAs. Stenotic NIRAs showed significantly reduced stress MBF, myocardial flow reserve (MFR), relative flow reserve (RFR) (0.72 ± 0.12 vs. 0.82 ± 0.14; p = 0.001), and stress kmono, as compared to those in non-stenotic NIRAs. NIRAs with significant stenosis had significantly lower stress MBF, MFR, and RFR (0.70 ± 0.10 vs. 0.80 ± 0.14; p = 0.001). RFR showed the best, but modest linear correlation with DS of NIRA stenosis (r = -0.429, p = 0.001). RFR > 0.81 could effectively exclude the presence of significant NIRA stenosis. CONCLUSIONS: C-11 acetate PET could be a feasible alternative noninvasive modality in patients with STEMI and multivessel disease, by excluding the presence of significant NIRA stenosis.

Precise characterization of a solitary pulmonary nodule using tumor shadow disappearance rate-corrected F-18 FDG PET and enhanced CT.

ABSTRACT: We aimed to characterize solitary pulmonary nodule (SPN) using imaging parameters for F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) or enhanced CT corrected by tumor shadow disappearance rate (TDR) to reflect the tissue density.We enrolled 51 patients with an SPN who underwent PET/CT and chest CT with enhancement. The FDG uptake of SPN was evaluated using maximum standardized uptake value (SUVmax) on PET/CT. The mean Hounsfield unit (HU) for each SPN was evaluated over the region of interest on nonenhanced and enhanced CT images. The change in mean HU (HUpeak-pre) was quantified by subtracting the mean HU of the preenhanced CT from that of the post-enhanced CT. TDR was defined as the ratio of the tumor area, which disappears at a mediastinal window, to the tumor area of the lung window. We investigated which parameters (SUVmax or HUpeak-pre) could contribute to the characterization of SPN classified by TDR value and whether diagnostic performance could be improved using TDR-corrected imaging parameters.For SPN with higher tissue density (TDR <42%, n = 22), high value of SUVmax (≥3.1) was a significant factor to predict malignancy (P = .006). High value of HUpeak-pre (≥38) was a significant factor to characterize SPN (P = .002) with lower tissue density (TDR ≥42%, n = 29). The combined approach using TDR-corrected parameters had better predictive performance to characterize SPN than SUVmax only (P = .031).Applying imaging parameters such as SUVmax or HUpeak-pre in consideration of tissue density calculated with TDR could contribute to accurate characterization of SPN.

Diagnostic Blood Biomarkers in Alzheimer's Disease.

Potential biomarkers for Alzheimer's disease (AD) include amyloid ß1-42 (Aß1-42), t-Tau, p-Tau181, neurofilament light chain (NFL), and neuroimaging biomarkers. Their combined use is useful for diagnosing and monitoring the progress of AD. Therefore, further development of a combination of these biomarkers is essential. We investigated whether plasma NFL/Aß1-42 can serve as a plasma-based primary screening biomarker reflecting brain neurodegeneration and amyloid pathology in AD for monitoring disease progression and early diagnosis. We measured the NFL and Aß1-42 concentrations in the CSF and plasma samples and performed correlation analysis to evaluate the utility of these biomarkers in the early diagnosis and monitoring of AD spectrum disease progression. Pearson's correlation analysis was used to analyse the associations between the fluid biomarkers and neuroimaging data. The study included 136 participants, classified into five groups: 28 cognitively normal individuals, 23 patients with preclinical AD, 22 amyloid-negative patients with amnestic mild cognitive impairment, 32 patients with prodromal AD, and 31 patients with AD dementia. With disease progression, the NFL concentrations increased and Aß1-42 concentrations decreased. The plasma and CSF NFL/Aß1-42 were strongly correlated (r = 0.558). Plasma NFL/Aß1-42 was strongly correlated with hippocampal volume/intracranial volume (r = 0.409). In early AD, plasma NFL/Aß1-42 was associated with higher diagnostic accuracy than the individual biomarkers. Moreover, in preclinical AD, plasma NFL/Aß1-42 changed more rapidly than the CSF t-Tau or p-Tau181 concentrations. Our findings highlight the utility of plasma NFL/Aß1-42 as a non-invasive plasma-based biomarker for early diagnosis and monitoring of AD spectrum disease progression.

Comparison of ¹³¹I whole-body imaging, ¹³¹I SPECT/CT, and ¹8F-FDG PET/CT in the detection of metastatic thyroid cancer.

PURPOSE: The aim of this study was to compare (131)I whole-body scintigraphy (WBS), WBS with (131)I single photon emission computed tomography/computed tomography (SPECT/CT), and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in the detection of distant metastases of differentiated thyroid cancer (DTC). METHODS: A total of 140 patients with 258 foci of suspected distant metastases were evaluated. (131)I WBS, (131)I SPECT/CT, and (18)F-FDG PET/CT images were interpreted separately. The final diagnosis was obtained from histopathologic study, serum thyroglobulin level, other imaging modalities, and/or clinical follow-up. RESULTS: Of the 140 patients with 258 foci, 46 patients with 166 foci were diagnosed as positive for distant metastasis. The sensitivity, specificity, and diagnostic accuracy of each imaging modality were 65, 55, and 59%, respectively, for (131)I WBS; 65, 95, and 85% for (131)I SPECT/CT, respectively; and 61, 98, and 86%, respectively, for (18)F-FDG PET/CT in patient-based analyses. Lesion-based analyses demonstrated that both SPECT/CT and PET/CT were superior to WBS (p<0.001) in all patient groups. SPECT/CT was superior to WBS and PET/CT (p<0.001) in patients who received a single challenge of radioiodine therapy, whereas PET/CT was superior to WBS (p=0.005) and SPECT/CT (p=0.013) in patients who received multiple challenges. CONCLUSION: Both SPECT/CT and PET/CT demonstrated high diagnostic performance in detecting metastatic thyroid cancer. SPECT/CT was highly accurate in patients who underwent a single challenge of radioiodine therapy. In contrast, (18)F-FDG PET/CT presented the highest diagnostic performance in patients who underwent multiple challenges of radioiodine therapy.

Change of Therapeutic Response Classification According to Recombinant Human Thyrotropin-Stimulated Thyroglobulin Measured at Different Time Points in Papillary Thyroid Carcinoma.

PURPOSE: We investigated whether response classification after total thyroidectomy and radioactive iodine (RAI) therapy could be affected by serum levels of recombinant human thyrotropin (rhTSH)-stimulated thyroglobulin (Tg) measured at different time points in a follow-up of patients with papillary thyroid carcinoma (PTC). METHODS: A total of 147 PTC patients underwent serum Tg measurement for response assessment 6 to 24 months after the first RAI therapy. Serum Tg levels were measured at 24 h (D1Tg) and 48-72 h (D2-3Tg) after the 2nd injection of rhTSH. Responses were classified into three categories based on serum Tg corresponding to the excellent response (ER-Tg), indeterminate response (IR-Tg), and biochemical incomplete response (BIR-Tg). The distribution pattern of response classification based on serum Tg at different time points (D1Tg vs. D2-3Tg) was compared. RESULTS: Serum D2-3Tg level was higher than D1Tg level (0.339 ng/mL vs. 0.239 ng/mL, P < 0.001). The distribution of response categories was not significantly different between D1Tg-based and D2-3Tg-based classification. However, 8 of 103 (7.8%) patients and 3 of 40 (7.5%) patients initially categorized as ER-Tg and IR-Tg based on D1Tg, respectively, were reclassified to IR-Tg and BIR-Tg based on D2-3Tg, respectively. The optimal cutoff values of D1Tg for the change of response categories were 0.557 ng/mL (from ER-Tg to IR-Tg) and 6.845 ng/mL (from IR-Tg to BIR-Tg). CONCLUSION: D1Tg measurement was sufficient to assess the therapeutic response in most patients with low level of D1Tg. Nevertheless, D2-3Tg measurement was still necessary in the patients with D1Tg higher than a certain level as response classification based on D2-3Tg could change.

Differences in diagnostic impact of dual-tracer PET/computed tomography according to the extrahepatic metastatic site in patients with hepatocellular carcinoma.

OBJECTIVES: We compared the diagnostic performance of C-11 acetate and F-18 fluorodeoxyglucose (FDG) PET/computed tomography (CT) for the detection of extrahepatic metastasis in patients with hepatocellular carcinoma (HCC) and evaluated whether the improvement in the diagnostic performance of dual tracer PET/CT differs by the metastatic site. METHODS: Fifty-eight patients who had extrahepatic metastasis on either C-11 acetate or F-18 FDG PET/CT were enrolled, and 193 metastatic lesions were analyzed in this retrospective study. The metastatic lesions were categorized based on six sites of involvement. According to each involved site, the tracer avidity of the metastatic lesions was compared using the maximum standardized uptake value (SUVmax). RESULTS: Bone was the most frequent categorized metastatic site (44.8%), followed by lymph node (39.7%), lung (34.5%), soft tissue (27.6%), adrenal gland (6.9%), and vascular category (3.4%). C-11 acetate PET/CT showed a higher SUVmax than F-18 FDG PET/CT in metastatic bone lesions (P = 0.003). F-18 FDG uptake was significantly higher than C-11 acetate uptake in metastatic lymph node lesions (P < 0.001). The detection rate of dual tracer PET/CT was significantly higher in the metastatic lung (93.6%) and soft tissue (100%) lesions. However, the diagnostic performance of dual tracer PET/CT was limited in the metastatic bone and lymph node lesions because each tracer's detection rate was very high (bone: 94.6% in C-11 acetate, lymph node: 94.1% in F-18 FDG). CONCLUSIONS: The tracer avidity of metastatic lesions differed according to the involved site. This difference affected the complementary role of dual tracer PET/CT in the diagnosis of extrahepatic metastases in patients with HCC.

Clonorchis sinensis-Derived Protein Attenuates Inflammation and New Bone Formation in Ankylosing Spondylitis.

Helminth infections and their components have been shown to have the potential to modulate and attenuate immune responses. The objective of this study was to evaluate the potential protective effects of Clonorchis sinensis-derived protein (CSp) on ankylosing spondylitis (AS). Cytotoxicity of CSp at different doses was assessed by MTS and flow cytometry before performing experiments. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analyzed using flow cytometry. The levels of INF- γ , IL-17A, TNF-α, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). SKG mice were treated with CSp or vehicles. Inflammation and new bone formation were evaluated using immunohistochemistry, positron emission tomography (PET), and micro-computed tomography (CT). Treatment with CSp resulted in no reduced cell viability of PBMCs or SFMCs until 24 h. In experiments culturing PBMCs and SFMCs, the frequencies of IFN- γ and IL-17A producing cells were significantly reduced after CSp treatment. In the SKG mouse model, CSp treatment significantly suppressed arthritis, enthesitis, and enteritis. Micro-CT analysis of hind paw revealed reduced new bone formation in CSp-treated mice than in vehicle-treated mice. We provide the first evidence demonstrating that CSp can ameliorate clinical signs and cytokine derangements in AS. In addition, such CSp treatment could reduce the new bone formation of AS.