215 results on '"Yen RF"'
Search Results
2. Correlation of F-18 fluorodeoxyglucose-positron emission tomography maximal standardized uptake value and EGFR mutations in advanced lung adenocarcinoma.
- Author
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Huang CT, Yen RF, Cheng MF, Hsu YC, Wei PF, Tsai YJ, Tsai MF, Shih JY, Yang CH, Yang PC, Huang, Chun-Ta, Yen, Rouh-Fang, Cheng, Mei-Fang, Hsu, Ya-Chieh, Wei, Pin-Fei, Tsai, Yi-Ju, Tsai, Meng-Feng, Shih, Jin-Yuan, Yang, Chih-Hsin, and Yang, Pan-Chyr
- Abstract
Objective: Epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma are involved in the tumorigenesis and regulation of cell metabolism via Akt signaling. F-18 fluorodeoxyglucose-positron emission tomography ([(18)F]FDG PET), a functional imaging modality, can be used to measure tumor cell metabolism. Thus, in this study, we hypothesize that there exist correlations between EGFR mutation status and [(18)F]FDG uptake of advanced lung adenocarcinoma.Methods: From May 2004 to April 2008, patients with stage IIIB or IV lung adenocarcinoma who underwent [(18)F]FDG PET and EGFR mutation analysis before receiving any treatment were eligible to participate in this study. The association of EGFR mutation status with patient characteristics and the SUV(MAX) from the [(18)F]FDG PET was evaluated. Multivariate logistic regression analysis was used to analyze predictors of EGFR mutations.Results: Seventy-seven lung adenocarcinoma patients were included in this study. EGFR mutations were identified in 49 (64%) of the patients. The [(18)F]FDG uptake was significantly higher in EGFR-mutant (mean SUV(MAX) = 10.5 +/- 4.7) than wild-type (8.0 +/- 3.3) lung adenocarcinoma patients (P = 0.008). The median SUV(MAX) was 9.5, and patients with an SUV(MAX) >or= 9.5 were more likely to harbor EGFR mutations (P = 0.009). In the multivariate analysis, an SUV(MAX) >or= 9.5 remained a statistically significant predictor of EGFR mutations (P = 0.005).Conclusions: Among Asian patients with advanced lung adenocarcinoma, those with higher SUV(MAX) on the [(18)F]FDG PET are more likely to carry EGFR mutations. [ABSTRACT FROM AUTHOR]- Published
- 2010
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3. Association of kidney function with residual hypertension after treatment of aldosterone-producing adenoma.
- Author
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Wu VC, Chueh SC, Chang HW, Lin LY, Liu KL, Lin YH, Ho YL, Lin WC, Wang SM, Huang KH, Hung KY, Kao TW, Lin SL, Yen RF, Chen YM, Hsieh BS, Wu KD, and TAIPAI Study Group
- Abstract
BACKGROUND: Autonomous secretion of aldosterone in patients with primary aldosteronism increases glomerular filtration rate and causes kidney damage. The influence of a mild decrease in kidney function on residual hypertension after adrenalectomy is unexplored. STUDY DESIGN: Nonconcurrent prospective study. SETTING & PARTICIPANTS: The study was based on the Taiwan Primary Aldosteronism Investigation (TAIPAI) database. 150 patients (61 men; overall mean age, 47.2 +/- 11.6 years) with a diagnosis of aldosterone-producing adenoma had undergone unilateral adrenalectomy at National Taiwan University Hospital from July 1999 to January 2007. PREDICTOR: Presurgery estimated glomerular filtration rate (eGFR). OUTCOMES & MEASUREMENTS: Residual hypertension after adrenalectomy, defined either as less than 75% of recorded blood pressure measurements with systolic blood pressure less than 140 mm Hg and diastolic blood pressure less than 90 mm Hg or requiring antihypertensive medications during the first year after surgery. RESULTS: Before surgery, 27 (18%), 72 (48%), and 51 (34%) patients had moderately to severely decreased (<60 mL/min/1.73 m(2)), mildly decreased (60
or=90 mL/min/1.73 m(2)), respectively. After surgery, 16 (59.3%), 29 (40.3%), and 10 (19.3%) patients in each category had postsurgery residual hypertension. Compared with patients without decreased eGFR before surgery, adjusted odds ratios for postsurgery residual hypertension were 2.7 (95% confidence interval, 1.03 to 7.0; P = 0.04) and 2.8 (95% confidence interval, 1.05 to 9.3) for mildly and moderately to severely decreased eGFR, respectively. LIMITATIONS: Arbitrary definition for residual hypertension. CONCLUSIONS: Two-thirds of patients with aldosterone-producing adenoma were cured of hypertension by means of unilateral adrenalectomy. Kidney function impairment, even mild, appears to be associated with a high incidence of postsurgery residual hypertension. Copyright © 2009 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR] - Published
- 2009
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4. Hemiballism in a patient with parietal lobe infarction.
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Wu MC, Yen RF, Lin CH, Wu RM, Nita DA, Wu, Meng-Chen, Yen, Ruoh-Fang, Lin, Chin-Hsien, and Wu, Ruey-Meei
- Published
- 2013
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5. Asymmetric intense bilateral adrenal uptake on [18F]fluorodeoxyglucose positron emission tomography/computed tomography in a patient with solitary pulmonary nodule.
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Cheng MF, Lin MW, Wu CT, Shih SR, Wu YW, Tzen KY, Yen RF, Cheng, Mei-Fang, Lin, Mong-Wei, Wu, Chen-Tu, Shih, Shyang-Rong, Wu, Yen-Wen, Tzen, Kai-Yuan, and Yen, Rouh-Fang
- Published
- 2012
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6. Clinical Application of 18F-3'-Fluoro-3'-Deoxy-L-thymidine (18F-FLT) Positron Emission Tomography (PET) in Lung Tumors
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Yen RF
- Published
- 2010
7. 18F-NaF PET in Detecting Metastatic Bone Lesion for Patients With Cancer.
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Far Eastern Memorial Hospital and Yen RF
- Published
- 2009
8. Cerebral tau pathology in cerebral amyloid angiopathy.
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Tsai HH, Liu CJ, Lee BC, Chen YF, Yen RF, Jeng JS, and Tsai LK
- Abstract
Tau, a hallmark of Alzheimer's disease, is poorly characterized in cerebral amyloid angiopathy. We aimed to assess the clinico-radiological correlations between tau positron emission tomography scans and cerebral amyloid angiopathy. We assessed cerebral amyloid and hyperphosphorylated tau in patients with probable cerebral amyloid angiopathy ( n = 31) and hypertensive small vessel disease ( n = 27) using
11 C-Pittsburgh compound B and18 F-T807 positron emission tomography. Multivariable regression models were employed to assess radio-clinical features related to cerebral tau pathology in cerebral amyloid angiopathy. Cerebral amyloid angiopathy exhibited a higher cerebral tau burden in the inferior temporal lobe [1.25 (1.17-1.42) versus 1.08 (1.05-1.22), P < 0.001] and all Braak stage regions of interest ( P < 0.05) than hypertensive small vessel disease, although the differences were attenuated after age adjustment. Cerebral tau pathology was significantly associated with cerebral amyloid angiopathy-related vascular markers, including cortical superficial siderosis ( β = 0.12, 95% confidence interval 0.04-0.21) and cerebral amyloid angiopathy score ( β = 0.12, 95% confidence interval 0.03-0.21) after adjustment for age, ApoE4 status and whole cortex amyloid load. Tau pathology correlated significantly with cognitive score (Spearman's ρ =-0.56, P = 0.001) and hippocampal volume (-0.49, P = 0.007), even after adjustment. In conclusion, tau pathology is more frequent in sporadic cerebral amyloid angiopathy than in hypertensive small vessel disease. Cerebral amyloid angiopathy-related vascular pathologies, especially cortical superficial siderosis, are potential markers of cerebral tau pathology suggestive of concomitant Alzheimer's disease., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)- Published
- 2024
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9. PET/MRI in Endometrial Cancer: Imaging Biomarkers are Associated with Disease Progression and Overall Survival.
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Shih IL, Yen RF, Chen CA, Cheng WF, Chen BB, Zheng QY, Cheng MF, Chen JL, and Shih TT
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- Humans, Female, Radiopharmaceuticals, Prospective Studies, Prognosis, Positron-Emission Tomography methods, Magnetic Resonance Imaging methods, Biomarkers, Disease Progression, Retrospective Studies, Tumor Burden, Positron Emission Tomography Computed Tomography, Fluorodeoxyglucose F18, Endometrial Neoplasms diagnostic imaging
- Abstract
Rationale and Objectives: To evaluate the association between positron emission tomography (PET)/magnetic resonance imaging (MRI) biomarkers and survival outcomes in patients with endometrial cancer., Materials and Methods: Between April 2014 and April 2016, 88 patients with newly diagnosed endometrial cancer participated this prospective study and underwent [
18 F] fluorodeoxyglucose PET/MRI. Sixty-nine patients with measurable tumors on PET/MRI were included in the image analysis. Imaging biomarkers included the minimum and mean apparent diffusion coefficients (ADCmin and ADCmean ), maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors. The log-rank test and Cox proportional hazards model were used to assess the relationship between imaging biomarkers and survival., Results: After a median follow-up of 80 months, 15 (22%) patients had tumor progression and six (9%) patients died. The results of ADCmin , ADCmean , and SUVmax did not show a significant association with progression-free survival (PFS) and overall survival (OS). Significantly shorter PFS was noted in patients with primary tumors with higher MTV (P < 0.001) and TLG (P < 0.001). Significantly shorter OS was also noted in patients with primary tumors with higher MTV (P = 0.048) and TLG (P = 0.034). In the multivariate analysis, MTV was an independent predictor of PFS (hazard ratio = 10.84, P = 0.033)., Conclusion: PET/MRI biomarkers, particularly MTV and TLG, are associated with PFS and OS in patients with endometrial cancer. MTV was an independent predictor of PFS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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10. Differences in lobar microbleed topography in cerebral amyloid angiopathy and hypertensive arteriopathy.
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Kuo PY, Tsai HH, Lee BC, Chiang PT, Liu CJ, Chen YF, Jeng JS, Yen RF, and Tsai LK
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- Humans, Cerebral Hemorrhage complications, Magnetic Resonance Imaging methods, Amyloid, Amyloidogenic Proteins, Arteriolosclerosis complications, Cerebral Amyloid Angiopathy complications, Cerebral Amyloid Angiopathy diagnostic imaging, Hypertension complications, Hypertension diagnostic imaging
- Abstract
Lobar cerebral microbleeds are a characteristic neuroimaging finding in cerebral amyloid angiopathy (CAA) but can also be found in hypertensive arteriolosclerosis. We aimed to investigate whether CAA is more associated with intracortical lobar microbleeds than hypertensive arteriosclerosis. Ninety-one survivors of spontaneous intracerebral hemorrhage with at least one lobar microbleed were included and underwent brain MRI and amyloid PET. We categorized lobar microbleeds as intracortical, juxtacortical, or subcortical. We assessed the associations between the lobar microbleed categories and microangiopathy subtypes or cerebral amyloid load based on the Pittsburgh Compound-B PET standardized uptake value ratio (SUVR). Patients with CAA had a higher prevalence of intracortical lobar microbleeds (80.0% vs. 50.8%, P = 0.011) and lower prevalence of subcortical lobar microbleeds (13.3% vs. 60.1%, P < 0.001) than patients with hypertensive arteriolosclerosis. Strictly intracortical/juxtacortical lobar microbleeds were associated with CAA (OR 18.9 [1.9-191.4], P = 0.013), while the presence of subcortical lobar microbleeds was associated with hypertensive arteriolosclerosis (OR 10.9 [1.8-68.1], P = 0.010). Amyloid retention was higher in patients with strictly intracortical/juxtacortical CMBs than those without (SUVR = 1.15 [1.05-1.52] vs. 1.08 [1.02-1.19], P = 0.039). Amyloid retention positively correlated with the number of intracortical lobar microbleeds (P < 0.001) and negatively correlated with the number of subcortical lobar microbleeds (P = 0.018). CAA and cortical amyloid deposition are more strongly associated with strictly intracortical/juxtacortical microbleeds than subcortical lobar microbleeds. Categorization of lobar microbleeds based on anatomical location may help differentiate the underlying microangiopathy and potentially improve the accuracy of current neuroimaging criteria for cerebral small vessel disease., (© 2024. The Author(s).)
- Published
- 2024
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11. In vivo detection of poststroke cerebral cell proliferation in rodents and humans.
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Chiang PT, Tsai HH, Yen RF, Tsai YC, Wu CH, Chiu CH, and Tsai LK
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- Humans, United States, Rats, Animals, Dideoxynucleosides, Cell Proliferation, Cerebral Infarction, Infarction, Rodentia, Stroke diagnostic imaging
- Abstract
Objective: F-18-fluorothymidine (FLT) is a positron emission tomography (PET) tracer for imaging cell proliferation in vivo. We aimed to assess FLT uptake as a marker for cerebral cell proliferation in a rat model of ischemic stroke and patients with cerebral infarct, correlating with disease severity and outcomes., Methods: Cerebral FLT PET was performed in rats subjected to transient middle cerebral artery occlusion (MCAO) and patients with cerebral infarct. PET data were analyzed and expressed as average standardized uptake value ratios (SUVRs) using cerebellar cortex as reference. Infarct volume was analyzed by 2,3,5-triphenyltetrazolium chloride staining in rats and by magnetic resonance imaging in patients. Neurological function was assessed using modified Neurological Severity Score (mNSS) for rats and National Institutes of Health Stroke Scale (NIHSS) for patients., Results: Seven days post-MCAO, rats' FLT PET displayed higher SUVRs in the infarcted brain, declining gradually until Day 28. FLT-binding ratio (SUVR in the infarcted brain divided by that in contralateral side) correlated positively with stroke severity (p < 0.001), and to early mNSS decline in rats with mild to moderate stroke severity (p = 0.031). In 13 patients with cerebral infarct, FLT PET showed high SUVR in the infarcted regions. FLT-binding ratio correlated positively with infarct volume (p = 0.006). Age-adjusted initial NIHSS (p = 0.035) and early NIHSS decline (p = 0.076) showed significance or a trend toward positive correlation with the FLT-binding ratio., Interpretation: In vivo FLT PET detects poststroke cerebral cell proliferation, which is associated with stroke severity and/or outcomes in MCAO rats and patients with cerebral infarct., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
- Published
- 2024
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12. Clinical practice consensus for the diagnosis and management of melanoma in Taiwan.
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Wu CE, Liao YH, Wu CL, Yen RF, Lin CC, Yang MH, Yen CC, Su WC, Yen CJ, Chang YF, Wu MF, Yang Y, Lin CY, Yang WC, Wang HC, Li CY, Ho YY, Chang YY, Wu CS, Hsu HC, Chen KH, Huang Y, Chen CJ, Chuang PJ, Lai YC, Huang YY, Tseng NC, Huang YT, Chu CY, and Wen-Cheng Chang J
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- Humans, Taiwan, Immunotherapy, Consensus, Melanoma diagnosis, Melanoma therapy, Skin Neoplasms diagnosis, Skin Neoplasms therapy, Skin Neoplasms genetics
- Abstract
Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)
- Published
- 2024
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13. Comparison of post-COVID-19 vaccination hypermetabolic lymphadenopathy on 18 F-fluorodeoxyglucose PET/CT between virus-vector vaccine and mRNA vaccine.
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Chiang MT, Wang JT, Lin WY, Yen RF, Huang JY, and Lu CC
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- Humans, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography methods, mRNA Vaccines, COVID-19 Vaccines adverse effects, 2019-nCoV Vaccine mRNA-1273, Retrospective Studies, Lymph Nodes diagnostic imaging, Vaccination, Glucose, COVID-19 prevention & control, Lymphadenopathy diagnostic imaging, Lymphadenopathy etiology, Vaccines
- Abstract
Purpose: We compared hypermetabolic lymphadenopathy (HLN) on
18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) after virus-vector and mRNA vaccines for coronavirus disease 2019 (COVID-19)., Methods: This retrospective study included 573 participants who underwent FDG PET/CT after receiving a virus-vector vaccine (ChAdOx1, AstraZeneca [AZ] group) or an mRNA vaccine (mRNA-1273, Moderna [M] group) from July 2021 to October 2021. The incidence and avidity of HLN were evaluated and correlated with clinical features and vaccine type. The final analysis was conducted with 263 participants in the AZ group and 310 participants in the M group., Results: The HLN incidence was significantly lower in the AZ group than in the M group (38/263 [14%] vs. 74/310 [24%], p = 0.006). The FDG avidity of HLN was comparable between the two groups. The HLN incidence in both groups was significantly higher within 4 weeks after the vaccination compared with more than 4 weeks. The HLN incidence within 4 weeks of the vaccination was significantly higher in the M group than in the AZ group (p = 0.008), whereas a difference in HLN incidence between the two groups was not observed after the same duration (p = 0.11)., Conclusions: The mRNA mRNA-1273 COVID-19 vaccine was found to be associated with higher glucose hypermetabolism in regional lymph nodes within the first 4 weeks compared with the virus-vector vaccine, as indicated by the presence of HLN on FDG PET/CT. The degree of glucose hypermetabolism was comparable between the two vaccines., (© 2023. The Author(s).)- Published
- 2023
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14. Cerebral amyloid deposition predicts long-term cognitive decline in hemorrhagic small vessel disease.
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Tsai YC, Tsai HH, Liu CJ, Lin SS, Chen YF, Jeng JS, Tsai LK, and Yen RF
- Abstract
Background: To investigate the association between cerebral amyloid deposition and long-term cognitive outcomes in patients with hemorrhagic small vessel disease (SVD) and survivors of intracerebral hemorrhage (ICH)., Methods: Patients experiencing an ICH without overt dementia were prospectively recruited (n = 68) for brain MRI and Pittsburgh compound B (PiB) positron emission tomography scans at baseline. Cognitive function was assessed using the mini-mental status examination (MMSE) and clinical dementia rating after an overall median follow-up of 3.8 years. A positive amyloid scan was defined as a global PiB standardized uptake value ratio >1.2. Associations between follow-up cognitive outcomes and neuroimaging markers were explored using multivariable Cox regression models., Results: PiB(+) patients were older (72.1 ± 7.8 vs. 59.9 ± 11.7, p = .002) and more frequently had cerebral amyloid angiopathy (CAA) (63.6% vs. 15.8%, p = .002) than PiB(-) patients. PiB(+) was associated with a higher risk of dementia conversion (32.9 vs. 4.0 per 100-person-years, hazard ratio [HR] = 15.7 [3.0-80.7], p = .001) and MMSE score decline (58.8 vs. 9.9 per 100-person-years, HR = 6.2 [1.9-20.0], p = .002). In the non-CAA subgroup (n = 52), PiB(+) remained an independent predictor of dementia conversion, p = .04). In the Cox models, PiB(+) was an independent predictor of dementia conversion (HR = 15.8 [2.6-95.4], p = .003) and MMSE score decline (HR = 5.7 [1.6-20.3], p = .008) after adjusting for confounders., Conclusions: Cerebral amyloid deposition potentially contributes to long-term cognitive decline in SVD-related ICH., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)
- Published
- 2023
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15. Myocardial Flow Assessment After Heart Transplantation Using Dynamic Cadmium-Zinc-Telluride Single-Photon Emission Computed Tomography With 201 Tl and 99m Tc Tracers and Validated by 13 N-NH 3 Positron Emission Tomography.
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Ko KY, Ko CL, Lee CM, Cheng JS, Wu YW, Hsu RB, Chen YS, Wang SS, Yen RF, and Cheng MF
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- Humans, Tomography, Emission-Computed, Single-Photon methods, Positron-Emission Tomography methods, Cadmium, Technetium Tc 99m Sestamibi, Heart Transplantation adverse effects, Myocardial Perfusion Imaging methods, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease surgery
- Abstract
Background: Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse form of vasculopathy and is the most common cause of long-term cardiovascular mortality in heart transplant patients. This study aimed to investigate the diagnostic performance of
99m Tc and201 Tl tracers in the assessment of CAV using cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) for myocardial blood flow (MBF) and myocardial flow reserve (MFR) quantification, which was further validated using13 N-NH3 positron emission tomography (PET)., Methods: Thirty-eight patients with prior heart transplantation who underwent CZT SPECT and13 N-NH3 PET dynamic scans were included in this study. CZT SPECT with99m Tc-sestamibi was used in the first 19 patients and201 Tl-chloride for the remaining patients. To determine the diagnostic accuracy of angiographically defined moderate-to-severe CAV, the analysis included patients who underwent angiographic examinations within 1 year of their second scan., Results: There were no significant differences in the patient characteristics between the201 Tl and99m Tc tracer groups. Both201 Tl and99m Tc CZT SPECT-derived stress MBF and MFR values globally and in 3 coronary territories showed good correlations with13 N-NH3 PET. The201 Tl and99m Tc cohorts did not differ significantly in the correlation coefficients of CZT SPECT versus PET for MBF and MFR, except for stress MBF (201 Tl:0.95 versus99m Tc:0.80, P =0.03).201 Tl and99m Tc CZT SPECT were satisfactory for detecting PET MFR <2.0 (201 Tl area under the curve, 0.92 [0.71-0.99],99m Tc area under the curve, 0.87 [0.64-0.97]) and angiographically defined moderate-to-severe CAV, and CZT SPECT results were comparable to that of13 N-NH3 PET (CZT area under the curve, 0.90 [0.70-0.99], PET area under the curve, 0.86 [0.64-0.97])., Conclusions: This small study suggests that CZT SPECT using201 Tl and99m Tc tracers showed comparable MBF and MFR, and the results correlated well with those of13 N-NH3 PET. Hence, CZT SPECT with201 Tl or99m Tc tracers can be used to detect moderate-to-severe CAV in patients with prior heart transplantation. However, validation using larger studies is warranted., Competing Interests: Disclosures None.- Published
- 2023
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16. Pretherapy 18 F-FDG PET/CT in Predicting Disease Relapse in Patients With Immunoglobulin G4-Related Disease: A Prospective Study.
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Cheng MF, Guo YL, Yen RF, Wu YW, and Wang HP
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- Male, Female, Humans, Middle Aged, Aged, Positron Emission Tomography Computed Tomography, Prospective Studies, Radiopharmaceuticals, Positron-Emission Tomography methods, Steroids, Prognosis, Retrospective Studies, Fluorodeoxyglucose F18, Immunoglobulin G4-Related Disease diagnostic imaging, Immunoglobulin G4-Related Disease drug therapy
- Abstract
Objective: To investigate whether the levels of inflammation detected by
18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) can predict disease relapse in immunoglobulin G4-related disease (IgG4-RD) patients receiving standard induction steroid therapy., Materials and Methods: This prospective study analyzed pretherapy FDG PET/CT images from 48 patients (mean age, 63 ± 12.9 years; 45 males and 3 females) diagnosed with IgG4-RD between September 2008 and February 2018, who subsequently received standard induction steroid therapy as the first-line treatment. Multivariable Cox proportional hazards models were used to identify the potential prognostic factors associated with relapse-free survival (RFS)., Results: The median follow-up time for the entire cohort was 1913 days (interquartile range [IQR], 803-2929 days). Relapse occurred in 81.3% (39/48) patients during the follow-up period. The median time to relapse was 210 days (IQR, 140-308 days) after completion of standardized induction steroid therapy. Among the 17 parameters analyzed, Cox proportional hazard analysis identified whole-body total lesion glycolysis (WTLG) > 600 on FDG-PET as an independent risk factor for disease relapse (median RFS, 175 vs. 308 days; adjusted hazard ratio, 2.196 [95% confidence interval: 1.080-4.374]; P = 0.030)., Conclusion: WTLG on pretherapy FDG PET/CT was the only significant factor associated with RFS in IgG-RD patients receiving standard steroid induction therapy., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 The Korean Society of Radiology.)- Published
- 2023
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17. Cerebral Venous Reflux and Cerebral Amyloid Angiopathy: An Magnetic Resonance Imaging/Positron Emission Tomography Study.
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Lee BC, Tsai HH, Liu CJ, Chen YF, Tsai LK, Jeng JS, and Yen RF
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- Humans, Cross-Sectional Studies, Magnetic Resonance Imaging, Cerebral Hemorrhage diagnostic imaging, Cerebral Hemorrhage complications, Positron-Emission Tomography, Cerebral Amyloid Angiopathy diagnostic imaging, Cerebral Amyloid Angiopathy complications
- Abstract
Background: Cerebral venous outflow alterations contribute to central nervous system pathology in aging and neurodegenerative disorders and are potentially linked to underlying cerebral microangiopathy. We investigated whether cerebral venous reflux (CVR) is more closely associated with cerebral amyloid angiopathy (CAA) than hypertensive microangiopathy in intracerebral hemorrhage (ICH) survivors., Methods: This cross-sectional study included 122 patients of spontaneous ICH with magnetic resonance and positron emission tomography imaging studies (2014-2022) in Taiwan. The presence of CVR was defined as abnormal signal intensity in the dural venous sinus or internal jugular vein on magnetic resonance angiography. Cerebral amyloid load was measured using the Pittsburgh compound B standardized uptake value ratio. Clinical and imaging characteristics associated with CVR were evaluated in univariable and multivariable analyses. In the subset of patients with CAA, we applied univariable and multivariable linear regression analyses to evaluate the association between CVR and cerebral amyloid retention., Results: Compared with patients without CVR (n=84, 64.5±12.1 years), patients with CVR (n=38, 69.4±11.5 years) were significantly more likely to have CAA-ICH (53.7% versus 19.8%; P< 0.001) and had a higher cerebral amyloid load (standardized uptake value ratio [interquartile range], 1.28 [1.12-1.60] versus 1.06 [1.00-1.14]; P< 0.001). In a multivariable model, CVR was independently associated with CAA-ICH (odds ratio, 4.81 [95% CI, 1.74-13.27]; P =0.002) after adjustment for age, sex and conventional small vessel disease markers. In CAA-ICH, higher PiB retention was observed in patients with CVR than patients without CVR (standardized uptake value ratio [interquartile range], 1.34 [1.08-1.56] versus 1.09 [1.01-1.26]; P <0.001). In multivariable analysis after adjustment for potential confounders, the presence of CVR was independently associated with a higher amyloid load (standardized β=0.40; P =0.001)., Conclusions: In spontaneous ICH, CVR is associated with CAA and a higher amyloid burden. Our results suggest venous drainage dysfunction potentially plays a role in CAA and cerebral amyloid deposition.
- Published
- 2023
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18. Predicting Treatment Response in Primary Aldosteronism Using 11 C-Metomidate Positron Emission Tomography.
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Lu CC, Chen CJ, Peng KY, Chueh JS, Chang CC, Yen RF, and Wu VC
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- Etomidate analogs & derivatives, Fluorodeoxyglucose F18, Humans, Positron-Emission Tomography methods, Prospective Studies, Adosterol, Hyperaldosteronism drug therapy, Hyperaldosteronism therapy
- Abstract
Background: Appropriate treatment of primary aldosteronism (PA) depends on accurate lateralization. 11 C-metomidate (MTO) is a tracer used in PET that provides functional information about the adrenal cortex. We aimed to perform MTO PET for patients with PA who are managed according to the guideline and to verify its correlation with other lateralization modalities and usefulness in outcome prediction., Methods: Seventeen patients with PA who underwent MTO PET and had ≥1 lateralization modality (adrenal venous sampling and/or NP-59 adrenal scintigraphy) were included. SUV max of each adrenal gland (higher uptake side, HSUV max ; lower uptake side, LSUV max ) and the ratio of HSUV max to LSUV max (contrast) were compared with lateralization modalities, postsurgical outcomes, and medical treatment outcomes. Cutoff values were used as outcome predictors., Results: HSUV max and LSUV max increased in the order of bilateral, unilateral, and negative findings of CT, with opposite order of contrast. High discordant rate between MTO PET and other lateralization modalities was noted. Biochemical responders (n = 8) had significantly lower HSUV max and LSUV max than nonresponders, and clinical responders (n = 6) had borderline lower HSUV max than nonresponders. By optimal cutoff values of HSUV max and LSUV max , MTO PET was able to predict biochemical and clinical outcomes in patients with medical treatment., Conclusion: According to adrenal CT findings, MTO PET presented different uptake patterns. Patients with PA under medical treatment showed significantly lower tracer uptake in responders. Thus, MTO PET may be a useful imaging biomarker to predict medical treatment outcome. Multicenter prospective study with a larger number of patients is needed for further validation., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflicts of interest. The study was funded by the Ministry of Science and Technology, Taiwan (106-2314-B-002-067)., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2022
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19. Neuroinflammation in Low-Level PM2.5-Exposed Rats Illustrated by PET via an Improved Automated Produced [ 18 F]FEPPA: A Feasibility Study.
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Cheng MF, Cheng TJ, Guo YL, Chiu CH, Wu HM, Yen RF, Huang YY, Huang WS, and Shiue CY
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- Animals, Feasibility Studies, Fluorine Radioisotopes, Particulate Matter toxicity, Rats, Reproducibility of Results, Neuroinflammatory Diseases, Positron-Emission Tomography methods
- Abstract
Background: [
18 F]FEPPA is a potent TSPO imaging agent that has been found to be a potential tracer for imaging neuroinflammation. In order to fulfill the demand of this tracer for preclinical and clinical studies, we have developed a one-pot automated synthesis with simplified HPLC purification of this tracer, which was then used for PET imaging of neuroinflammation in fine particulate matter- (PM2.5-) exposed rats., Results: Using this automated synthesis method, the RCY of the [18 F]FEPPA was 38 ± 4% ( n = 17, EOB) in a synthesis time of 83 ± 8 min from EOB. The radiochemical purity and molar activities were greater than 99% and 209 ± 138 GBq/ μ mol (EOS, n = 15), respectively. The quality of the [18 F]FEPPA synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18 F]FEPPA was stable at 21 ± 2°C for up to 4 hr after the end of synthesis (EOS). Moreover, microPET imaging showed that increased tracer activity of [18 F]FEPPA in the brain of PM2.5-exposed rats ( n = 6) were higher than that of normal controls ( n = 6) and regional-specific., Conclusions: Using the improved semipreparative HPLC purification, [18 F]FEPPA has been produced in high quantity, high quality, and high reproducibility and, for the first time, used for PET imaging the effects of PM2.5 in the rat brain. It is ready to be used for imaging inflammation in various clinical or preclinical studies, especially for nearby PET centers without cyclotrons., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Mei-Fang Cheng et al.)- Published
- 2022
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20. [Normal and Near Normal Myocardial Perfusion Imaging Data Analysis: Two-Year Major Adverse Cardiac Event].
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Tang LH, Huang YH, Chen CJ, Yen RF, Tsai MH, and Chen CC
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- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Retrospective Studies, Stroke Volume, Ventricular Function, Left, Coronary Artery Disease diagnostic imaging, Myocardial Perfusion Imaging methods
- Abstract
Background: Myocardial perfusion imaging (MPI) is the method most commonly used to assess patients with suspected coronary artery disease for the presence of myocardial ischemia and risk of subsequent adverse cardiac events. Studies are limited on the incidence of major adverse cardiac event (MACE) in patients with normal MPI results., Purpose: The aim of this study was to investigate the incidence and risk factors of MACE in patients with normal or near-normal MPI results., Methods: In this single-center retrospective chart review study, patients who had received MPI tests at a nuclear medicine department of a medical center in 2017 were consecutively enrolled. All of the participants in this study were patients with normal or near-normal MPI results, and were followed for two years to assess the incidence of MACE (death, hospitalized for percutaneous coronary intervention; CABG, heart failure and stroke). Participants with or without MACE were compared to determine whether demographic, comorbidity, and MPI data were significant risk factors., Results: Of the 1,629 participants (age = 70.4 ± 11.3 years, 49.4% male) enrolled, 387 (23.8%) were classified into the normal MPI group and 1,242 (76.2%) were classified into the near-normal MPI group. Notably, 61 participants (15.8%) in the normal MPI group and 206 (16.6%) in the near-normal MPI group experienced MACE events during the two-year follow-up. The risk factors of MACE identified in this study included being older in age, being male, and having poor myocardial perfusion parameters (i.e., ejection fraction) during MPI., Conclusions / Implications for Practice: Over the two-year study period, 15.8% of the participants with normal MPI results and 16.6% of those with near-normal MPI results experienced major adverse cardiac events. Thus, it is critical to inform patients regarding the potential risk of MACE risk and to educate them on how to mitigate this risk by actively managing their hyperlipidemia level and left ventricular ejection fraction.
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- 2022
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21. Prognostic Value of Interim 18F-DOPA and 18F-FDG PET/CT Findings in Stage 3-4 Pediatric Neuroblastoma.
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Ko KY, Yen RF, Ko CL, Chou SW, Chang HH, Yang YL, Jou ST, Hsu WM, and Lu MY
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- Child, Dihydroxyphenylalanine, Humans, Positron Emission Tomography Computed Tomography, Prognosis, Retrospective Studies, Fluorodeoxyglucose F18, Neuroblastoma diagnostic imaging
- Abstract
Purpose: This retrospective study aimed to determine the prognostic value of imaging parameters derived from midtherapy 18F-fluorodihydroxyphenylalanine (18F-DOPA) and 18F-FDG PET in pediatric patients with stage 3-4 neuroblastoma., Methods: We enrolled 32 stage 3-4 pediatric neuroblastoma patients who underwent 18F-DOPA and 18F-FDG PET/CT scans before and after 3 chemotherapy cycles. We measured metabolic and volumetric parameters and applied a metabolic burden scoring system to evaluate the primary tumor extent and soft tissue metastases and that of bone/bone marrow involvement. The associations between these parameters and clinical outcomes were investigated., Results: Over a median follow-up period of 47 months (range, 3-137 months), 16 patients experienced disease progression, and 13 died. After adjustment for clinical factors, multivariate Cox proportional hazard models showed that interim tumor FDG/FDOPA SUVmax (hazard ratio [HR], 5.94; 95% confidence interval [CI], 1.10-34.98) and interim FDOPA whole-body metabolic burden scores (WBMB) (HR, 7.30; 95% CI, 1.50-35.50) were significant prognostic factors for overall survival (OS). Only interim FDOPA WBMB scores (HR, 7.05; 95% CI, 1.02-48.7) were predictive of progression-free survival. Based on median cutoff values, prognosis (OS and progression-free survival) was significantly associated with an interim FDOPA WBMB score ≥21.92 (all P < 0.05) and interim tumor FDG/FDOPA (SUVmax) score ≥0.57 with poor OS (P < 0.05)., Conclusions: Our results indicate that midtreatment FDG and FDOPA PET/CT could serve as prognostic markers in stage 3-4 neuroblastoma patients., Competing Interests: Conflicts of interest and sources of funding: This study was funded by the Ministry of Science and Technology, Taiwan under grant MOST 106-2314-B-002-185-MY2. The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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22. Plasma soluble TREM2 is associated with white matter lesions independent of amyloid and tau.
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Tsai HH, Chen YF, Yen RF, Lo YL, Yang KC, Jeng JS, Tsai LK, and Chang CF
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- Aged, Alzheimer Disease blood, Amyloid metabolism, Biomarkers blood, Cerebral Amyloid Angiopathy blood, Cerebral Small Vessel Diseases blood, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Positron-Emission Tomography, tau Proteins metabolism, Alzheimer Disease pathology, Cerebral Amyloid Angiopathy pathology, Cerebral Small Vessel Diseases pathology, Membrane Glycoproteins blood, Receptors, Immunologic blood, White Matter pathology
- Abstract
Cerebral small vessel disease is one of the most common causes of cognitive decline and stroke. While several lines of evidence have established a relationship between inflammation and cerebrovascular pathology, the mechanistic link has not yet been elucidated. Recent studies suggest activation of immune mediators, including the soluble form of triggering receptor expressed on myeloid cells 2 (TREM2), may be critical regulators. In this study, we compared the plasma levels of soluble TREM2 and its correlations with neuroimaging markers and cerebral amyloid load in 10 patients with Alzheimer's disease and 66 survivors of spontaneous intracerebral haemorrhage with cerebral amyloid angiopathy or hypertensive small vessel disease, two of the most common types of sporadic small vessel disease. We performed brain MRI and 11C-Pittsburgh compound B PET for all participants to evaluate radiological small vessel disease markers and cerebral amyloid burden, and 18F-T807 PET in a subgroup of patients to evaluate cortical tau pathology. Plasma soluble TREM2 levels were comparable between patients with Alzheimer's disease and small vessel disease (P = 0.690). In patients with small vessel disease, plasma soluble TREM2 was significantly associated with white matter hyperintensity volume (P < 0.001), but not with cerebral amyloid load. Among patients with Alzheimer's disease and cerebral amyloid angiopathy, plasma soluble TREM2 was independently associated with a tau-positive scan (P = 0.001) and white matter hyperintensity volume (P = 0.013), but not amyloid load (P = 0.221). Our results indicate plasma soluble TREM2 is associated with white matter hyperintensity independent of amyloid and tau pathology. These findings highlight the potential utility of plasma soluble TREM2 as a strong predictive marker for small vessel disease-related white matter injury and hold clinical implications for targeting the innate immune response when treating this disease., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
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23. Factors predicting one or two sentinel lymph nodes to be accepted for sentinel lymph node biopsy alone after neoadjuvant therapy in initially node-positive breast cancer patients.
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Tsai LW, Lee YH, Lo C, Lien HC, Wang MY, Jan IS, Yen RF, Hu FC, and Huang CS
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- Adult, Aged, Aged, 80 and over, Breast Neoplasms drug therapy, Breast Neoplasms surgery, Bridged-Ring Compounds therapeutic use, Databases, Factual, Female, Humans, Middle Aged, Neoadjuvant Therapy, Risk Assessment methods, Sensitivity and Specificity, Taiwan, Taxoids therapeutic use, Young Adult, Breast Neoplasms pathology, Sentinel Lymph Node pathology, Sentinel Lymph Node Biopsy statistics & numerical data
- Abstract
Background: Current guidelines recommend harvesting ≥3 sentinel nodes if sentinel lymph node biopsy (SLNB) alone is considered after neoadjuvant therapy (NAT) for initially node-positive (cN+) breast cancer. We attempted to investigate factors predicting one or two sentinel lymph nodes harvested to be accepted for SLNB alone after NAT in initially cN + patients., Methods: Overall, 157 patients who received NAT (clinically T1-3/N1-2/M0) and underwent SLNB were identified from a prospectively maintained database. Significant factors were identified using a multiple logistic regression model., Results: The overall SLN identification rate was 83.4%. Failed SLN identification was associated with a 2-day protocol using a single tracer (odds ratio: 0.331 [95% confidence interval {CI}: 0.132-0.830], p = 0.018), age >52 years (0.345 [0.131-0.913], p = 0.032), and lobular histology (0.156 [0.026-0.944], p = 0.043). The overall false-negative SLNB rate was 14.7%. Its increased risk was associated with radioactivity count >530 for any SLN during SLNB (96.4 [4.00-2320], p = 0.005), age ≥57 years (34.2 [1.92-610], p = 0.016), and taxane use (105 [1.02-10700], p = 0.049); its decreased risk was associated with more harvested SLNs (0.191 [0.054-0.669], p = 0.01) and dual tracers (0.101 [0.012-0.843], p = 0.034). A predictive model using these factors achieved an area under the curve of 0.935 (95% CI: 0.878-0.991)., Conclusion: When taxane was administered during NAT, the false-negative rate was predicted at <5% for patients aged <57 years, if 1-2 SLNs were harvested using dual tracers, and when the count of every SLN was lower than 530 after NAT in cN + breast cancer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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24. Diagnostic Performance of Proton Magnetic Resonance Spectroscopy and 18F-Fluorocholine PET to Differentiate Benign From Malignant Breast Lesions.
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Wu LA, Yen RF, Shih TT, Chen KL, and Wang J
- Subjects
- Female, Humans, Positron-Emission Tomography, Proton Magnetic Resonance Spectroscopy, Sensitivity and Specificity, Breast Neoplasms diagnostic imaging, Choline analogs & derivatives
- Abstract
Purpose: The aim of this study was to evaluate the diagnostic performance of the proton magnetic resonance spectroscopy (MRS) and 18F-fluorocholine (FCH) PET for suspicious breast findings on conventional imaging (mammography and breast ultrasound)., Methods: From September 2012 to December 2015, 37 women with 39 breast lesions on conventional imaging were enrolled and underwent proton MRS and FCH PET. The MRS parameters of choline signal-to-noise ratio (SNR), choline integral (I(cho)), and the PET parameters including SUVmax in the prone (SUV1) and supine (SUV2) positions were analyzed. Receiver operating characteristic curves with the area under the curve, sensitivity, and specificity under the optimal cutoff points for the different parameters were determined., Results: Twenty-three lesions (59%) were malignant, and 16 (41.0%) were benign. The malignant lesions tended to show significantly higher MRS and PET parameters than benign lesions (choline SNR, P = 0.007; I(cho), P = 0.003; SUV1 and SUV2, P < 0.0001). Fair to moderate correlations were noted between the choline SNR and PET parameters (SUV1, Spearman rank correlation coefficient, ρ = 0.477; SUV2, ρ = 0.483), as well as I(cho) and PET parameters (SUV1, ρ = 0.493; SUV2, ρ = 0.549). The SUV2 showed the highest diagnostic performance (area under the curve, 0.918). Using 2.5 as the optimal cutoff point, the SUV2 yields 89.5% sensitivity and 87.5% specificity for differentiating malignant from benign lesions., Conclusion: The MRS parameters were fairly to moderately correlated with FCH PET parameters, and both could differentiate malignant from benign breast lesions with SUV2 showing best diagnostic performance., Competing Interests: Conflicts of interest and sources of funding: The study was partially funded by the Ministry of Science and Technology, Taiwan (grant 101-2314-B-002-147-)., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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25. Long-term prognostic value of computed tomography-based attenuation correction on thallium-201 myocardial perfusion imaging: A cohort study.
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Huang JY, Yen RF, Huang CK, Liu CJ, Cheng MF, Chien KL, and Wu YW
- Subjects
- Aged, Coronary Artery Disease mortality, Female, Humans, Male, Middle Aged, Prognosis, Survival Rate, Thallium Radioisotopes, Coronary Artery Disease diagnostic imaging, Myocardial Perfusion Imaging, Tomography, X-Ray Computed
- Abstract
Background: Myocardial perfusion imaging (MPI) is a well-established diagnostic tool to evaluate coronary artery disease (CAD) and also an effective prognostic tool for patients with CAD. However, few studies investigated the prognostic value of attenuation correction (AC) in MPI, and the results were controversial., Objectives: To investigate the prognostic value of computed tomography (CT)-based AC thallium-201 (Tl-201) MPI., Methods: A total of 108 consecutive patients who underwent Tl-201 MPI and received coronary angiography within 90 days were included. Medical records were reviewed and missing information was completed after telephone contact. The prognostic value was evaluated by Kaplan-Meier analysis, univariable and multivariable Cox proportional hazards model., Results: After a mean follow-up of 7.72 ± 3.72 years, 27 patients had died, 41 had been readmitted for cardiovascular (CV)-related events and 44 had reached the composite of death plus CV-related re-admission. Kaplan-Meier curves for all-cause mortality for SSS with a cutoff value of 13 for AC and 16 for non-AC (NAC) images showed a significant difference between the two curves for both AC and NAC images (p = 0.011 for AC and p = 0.021 for NAC). In the multivariable model, SSS and SRS showed similar independent predictive values in predicting all-cause mortality and composite of all-cause mortality plus CV-related re-admission, in both AC and NAC images. Subgroup analysis implicated that AC MPI possibly provided better risk stratification in obese patients., Conclusion: CT-based AC and NAC MPI showed similar value and were the only significant predictors for the composite of mortality and CV events., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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26. Diagnostic Effect of Attenuation Correction in Myocardial Perfusion Imaging in Different Coronary Arteries: A Systematic Review and Meta-Analysis.
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Huang JY, Huang CK, Yen RF, Chien KL, and Wu YW
- Abstract
Background: The aim of this study was to determine whether, and if so how, attenuation correction (AC) improves the diagnostic performance of myocardial perfusion imaging (MPI) in different coronary artery-supplied territories, using coronary angiography as the reference standard. Methods: PubMed and EMBASE were searched until December 2020 for studies evaluating AC MPI for the diagnosis of coronary artery disease (CAD) with vessel-based data. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. For each study, the sensitivity, specificity, diagnostic odds ratios and areas under summary receiver operating characteristic curves (AUC) with 95% confidence intervals were calculated to determine the diagnostic accuracy of AC compared to non-AC MPI. A bivariate mixed-effects model was used to pool the data. Subgroup analyses considering the type of radiotracer and type of AC were performed. Results: A total of 264 articles were screened, of which 22 studies (2,608 patients) were enrolled. Significant improvements in specificity [0.78 vs. 0.58 in overall CAD, 0.87 vs. 0.61 in right coronary artery (RCA)] and diagnostic odds ratios (16 vs. 8 in overall CAD, 18 vs. 7 in RCA) after AC were shown in overall CAD at a patient level and RCA stenosis. Improvements in AUC were also noted. MPI had a similar diagnostic performance for detecting left anterior descending and left circumflex coronary artery stenosis with or without AC. There were trends of decreased sensitivity after AC, but none were significant. Diagnostic odds ratio showed significant improvement after AC only in the technetium-99m subgroup. Conclusion: The results of this study suggest that AC should be applied to MPI to improve the diagnosis of CAD regardless of which type of radiotracer, and that AC MPI can improve the specificity of detecting RCA stenosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Huang, Yen, Chien and Wu.)
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- 2021
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27. Preoperative 2-[ 18 F]FDG PET-CT aids in the prognostic stratification for patients with primary ampullary carcinoma.
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Chuang PJ, Wang HP, Lin YJ, Chen CC, Tien YW, Hsieh MS, Yang SH, Yen RF, Ko CL, Wu YW, and Cheng MF
- Subjects
- Female, Fluorodeoxyglucose F18, Humans, Male, Neoplasm Recurrence, Local, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Prognosis, Radiopharmaceuticals, Retrospective Studies, Tomography, X-Ray Computed, Tumor Burden, Ampulla of Vater diagnostic imaging, Lung Neoplasms
- Abstract
Objectives: We sought to investigate whether preoperative dual-phase 2-[
18 F]FDG PET-CT identify predictors for poor survival in patients with ampullary carcinoma receiving pancreaticoduodenectomy., Methods: The preoperative PET-CT images of patients with resected ampullary carcinoma from June 2007 to July 2017 were analyzed. Survival curves were analyzed using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard model was used to identify potential prognostic factors associated with disease-free survival (DFS) and overall survival (OS)., Results: Fifty-four subjects (26 men, 28 women) were enrolled with a median tumor size of 20 mm. All patients were followed for a median period of 36.9 months with 3- and 5-year DFS of 50.3% and 44.2%, and OS of 77.0% and 68.2%, respectively. Parameters associated with DFS in multivariate analysis were lymphovascular invasion (hazard ratio [HR]: 9.45, p < 0.001), involved margin in pathology (HR: 7.67, p < 0.001), and tumor retention index (RI) from the dual-phase PET (HR: 2.41, p = 0.03), whereas involved margin (HR: 13.14, p < 0.001), post-recurrence chemotherapy (HR: 0.10, p < 0.001), and metabolic tumor volume (MTV) (HR: 4.62, p = 0.009) emerged as independent prognostic factors for OS., Conclusions: Preoperative 2-[18 F]FDG PET-CT offered independent prognostic biomarkers in patients with ampullary carcinoma receiving standard surgical resection., Key Points: • 2-[18 F]FDG PET-CT offers good survival prediction before operation in primary malignant neoplasms at ampulla of Vater. • Dual-phase PET scan with bowel distention can better delineate Ampulla of Vater and characterize tumor physiology. • Preoperative risk stratification might aid in better treatment planning., (© 2021. European Society of Radiology.)- Published
- 2021
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28. Effects of Focal Radiation on [ 18 F]-Fluoro-D-Glucose Positron Emission Tomography in the Brains of Miniature Pigs: Preliminary Findings on Local Metabolism.
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Yeh CI, Cheng MF, Xiao F, Chen YC, Liu CC, Chen HY, Yen RF, Ju YT, Chen Y, Bodduluri M, Yu PH, Chi CH, Chong NS, Wu LH, Adler JR Jr, and Schneider MB
- Subjects
- Animals, Brain diagnostic imaging, Fluorodeoxyglucose F18, Positron-Emission Tomography, Swine, Swine, Miniature, Tomography, X-Ray Computed, Glucose, Positron Emission Tomography Computed Tomography
- Abstract
Objectives: It would be a medically important advance if durable and focal neuromodulation of the brain could be delivered noninvasively and without ablation. This ongoing study seeks to elucidate the effects of precisely delivered ionizing radiation upon focal brain metabolism and the corresponding cellular integrity at that target. We hypothesize that focally delivered ionizing radiation to the brain can yield focal metabolic changes without lesioning the brain in the process., Materials and Methods: We used stereotactic radiosurgery to deliver doses from 10 Gy to 120 Gy to the left primary motor cortex (M1) of Lee Sung miniature pigs (n = 8). One additional animal served as a nonirradiated control. We used positron emission tomography-computed tomography (PET-CT) to quantify radiation dose-dependent effects by calculating the ratio of standard uptake values (SUV) of 2-deoxy-2-[
18 F]-fluoro-D-glucose (18 F-FDG) between the radiated (left) and irradiated (right) hemispheres across nine months., Results: We found that the FDG-PET SUV ratio at the targeted M1 was significantly lowered from the pre-radiation baseline measurements for animals receiving 60 Gy or higher, with the effect persisting at nine months after radiosurgery. Only at 120 Gy was a lesion suggesting ablation visible at the M1 target. Animals treated at 60-100 Gy showed a reduced signal in the absence of an identifiable lesion, a result consistent with the occurrence of neuromodulation., Conclusion: Focal, noninvasive, and durable changes in brain activity can be induced without a magnetic resonance imaging (MRI)-visible lesion, a result that may be consistent with the occurrence of neuromodulation. This approach may provide new venues for the investigation of neuromodulatory treatments for disorders involving dysfunctional brain circuits. Postmortem pathological analysis is needed to elucidate whether there have been morphological changes not detected by MRI., (© 2020 International Neuromodulation Society.)- Published
- 2021
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29. Centrum Semiovale Perivascular Space and Amyloid Deposition in Spontaneous Intracerebral Hemorrhage.
- Author
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Tsai HH, Pasi M, Tsai LK, Huang CC, Chen YF, Lee BC, Yen RF, Gurol ME, and Jeng JS
- Subjects
- Aged, Aged, 80 and over, Cerebral Amyloid Angiopathy epidemiology, Cerebral Amyloid Angiopathy metabolism, Cerebral Cortex metabolism, Cerebral Hemorrhage epidemiology, Cerebral Hemorrhage metabolism, Female, Glymphatic System metabolism, Humans, Magnetic Resonance Imaging methods, Male, Middle Aged, Positron-Emission Tomography methods, Prospective Studies, White Matter metabolism, Cerebral Amyloid Angiopathy diagnostic imaging, Cerebral Cortex diagnostic imaging, Cerebral Hemorrhage diagnostic imaging, Glymphatic System diagnostic imaging, White Matter diagnostic imaging
- Abstract
Background and Purpose: We explored whether high-degree magnetic resonance imaging–visible perivascular spaces in centrum semiovale (CSO) are more prevalent in cerebral amyloid angiopathy (CAA) than hypertensive small vessel disease and their relationship to brain amyloid retention in patients with primary intracerebral hemorrhage (ICH)., Methods: One hundred and eight spontaneous ICH patients who underwent magnetic resonance imaging and Pittsburgh compound B were enrolled. Topography and severity of enlarged perivascular spaces were compared between CAA-related ICH (CAA-ICH) and hypertensive small vessel disease–related ICH (non-CAA ICH). Clinical and image characteristics associated with high-degree perivascular spaces were evaluated in univariate and multivariable analyses. Univariate and multivariable models were performed to evaluate associations between the severity of perivascular spaces in CSO and amyloid retention in CAA-ICH and non–CAA-ICH cases., Results: Patients with CAA-ICH (n=29) and non–CAA-ICH (n=79) had similar prevalence of high-degree perivascular spaces in CSO (44.8% versus 36.7%; P=0.507) and in basal ganglia (34.5% versus 51.9%; P=0.131). High-degree perivascular spaces in CSO were independently associated with the presence of lobar microbleed (odds ratio, 3.0 [95% CI, 1.1–8.0]; P=0.032). The amyloid retention was higher in those with high-degree than those with low-degree CSO-perivascular spaces in CAA-ICH (global Pittsburgh compound B standardized uptake value ratio, 1.55 [1.33–1.61] versus 1.13 [1.01–1.48]; P=0.003) but not in non–CAA-ICH. In CAA-ICH, the association between cerebral amyloid retention and the degree of perivascular spaces in CSO remained significant after adjustment for age and lobar microbleed number (P=0.004)., Conclusions: Although high-degree magnetic resonance imaging–visible perivascular spaces are equally prevalent between CAA-ICH and non–CAA-ICH in the Asian cohort, the severity of magnetic resonance imaging–visible CSO-perivascular spaces may be an indicator of higher brain amyloid deposition in patients with CAA-ICH.
- Published
- 2021
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30. A Double-Blind, Randomized, Controlled Trial of Lovastatin in Early-Stage Parkinson's Disease.
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Lin CH, Chang CH, Tai CH, Cheng MF, Chen YC, Chao YT, Huang TL, Yen RF, and Wu RM
- Subjects
- Double-Blind Method, Follow-Up Studies, Humans, Lovastatin therapeutic use, Mental Status and Dementia Tests, Parkinson Disease diagnostic imaging, Parkinson Disease drug therapy
- Abstract
Background: Recent evidence indicates that lipophilic statins have a neuroprotective benefit in animal models of Parkinson's disease (PD). The objective of this study was to evaluate whether lovastatin has the potential to slow motor symptom progression in patients with early-stage PD., Methods: This double-blind, randomized, placebo-controlled trial enrolled 77 patients with early-stage PD between May 23, 2017, and July 12, 2018, with follow-up ending September 1, 2019. Lovastatin 80 mg/day or placebo with 1:1 randomization was administered for 48 weeks. Mean change in the parts I-III scores of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), changes in the striatal dopamine uptake ratio measured by
18 F-dopa PET scan, and changes in PD medications between baseline and the week 48 visit were measured., Results: Of the 77 randomized patients, 70 (90.9%) completed the study. There was a slightly beneficial trend of the MDS-UPDRS motor score in the lovastatin group (-3.18 ± 5.50) compared with the placebo group (-0.50 ± 6.11); P = 0.14 adjusted for age, sex, disease duration, and baseline LEDD. Mean percentage change in the striatal18 F-dopa uptake ratio deteriorated less in the lovastatin group than in the placebo group on the dominant side of caudate (1.2% ± 7.3% vs -7.1% ± 8.2%, P < 0.01) and putamen (2.3% ± 7.1% vs -6.4% ± 8.1%, P < 0.01). We found no between-group differences in the change in part I or part II MDS-UPDRS scores. Lovastatin was generally well tolerated., Conclusions: Lovastatin treatment in patients with early-stage PD was associated with a trend of less motor symptom worsening and was well tolerated. A future larger long-term follow-up study is needed to confirm our findings. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)- Published
- 2021
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31. 2021 Advocacy Statements for the Role of 99m Tc-Pyrophosphate Scintigraphy in the Diagnosis of Transthyretin Cardiac Amyloidosis: A Report of the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China.
- Author
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Huang YH, Lin YH, Yen RF, Hou CJ, Wang SY, Tsai SC, Ho KC, Lin MH, Tsao CH, Chang CY, Huang JL, Cheng MF, and Wu YW
- Abstract
Transthyretin cardiac amyloidosis (ATTR-CM) is an increasingly recognized cause of heart failure with preserved ejection fraction. Favorable prognosis depends on early diagnosis and correct treatment strategy. Among patients for whom there is a high clinical suspicion of cardiac amyloidosis,
99m Tc-labeled bone avid scintigraphy including99m Tc-pyrophosphate (PYP) scintigraphy may be of diagnostic and prognostic importance. Various international guidelines support the non-biopsy diagnosis of ATTR-CM using99m Tc-PYP scintigraphy, yet emphasize the gap in standardization of acquisition and imaging analysis protocols, as well as the appropriateness of its clinical use. Therefore, a joint expert consensus has been reached by the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China, to advocate for the application of99m Tc-PYP scintigraphy in the diagnosis of ATTR-CM. This article aims to highlight the recommendations on image acquisition, qualitative and quantitative assessments of cardiac99m Tc-PYP uptake, and diagnostic algorithms. We hope the implementation of these recommendations in Taiwan will facilitate the process and enhance the diagnostic rate of ATTR-CM.- Published
- 2021
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32. NP-59 Adrenal Scintigraphy as an Imaging Biomarker to Predict KCNJ5 Mutation in Primary Aldosteronism Patients.
- Author
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Lu CC, Yen RF, Peng KY, Huang JY, Wu KD, Chueh JS, and Lin WY
- Subjects
- Adrenal Cortex Neoplasms diagnostic imaging, Adrenal Cortex Neoplasms metabolism, Adrenal Glands metabolism, Adrenalectomy, Adrenocortical Adenoma diagnostic imaging, Adrenocortical Adenoma metabolism, Adult, Female, Humans, Hyperaldosteronism metabolism, Male, Middle Aged, Mutation, Phenotype, Point Mutation, Precision Medicine, Predictive Value of Tests, ROC Curve, Tomography, Emission-Computed, Single-Photon, Adosterol pharmacology, Adrenal Glands diagnostic imaging, G Protein-Coupled Inwardly-Rectifying Potassium Channels biosynthesis, Hyperaldosteronism diagnostic imaging, Radionuclide Imaging methods
- Abstract
Purpose: Somatic KCNJ5 mutation occurs in half of unilateral primary aldosteronism (PA) and is associated with more severe phenotype. Mutation status can only be identified by tissue sample from adrenalectomy. NP-59 adrenal scintigraphy is a noninvasive functional study for disease activity assessment. This study aimed to evaluate the predictive value of NP-59 adrenal scintigraphy in somatic KCNJ5 mutation among PA patients who received adrenalectomy., Methods: Sixty-two PA patients who had NP-59 adrenal scintigraphy before adrenalectomy with available KCNJ5 mutation status were included. Two semiquantitative parameters, adrenal to liver ratio (ALR) and lesion to contralateral ratio of bilateral adrenal glands (CON) derived from NP-59 adrenal scintigraphy, of mutated and wild-type patients were compared. Cutoff values calculated by receiver-operating characteristic (ROC) analysis were used as a predictor of KCNJ5 mutation., Results: Twenty patients had KCNJ5 mutation and 42 patients were wild type. Patients harboring KCNJ5 mutation had both higher ALR and CON (p = 0.0031 and 0.0833, respectively) than wild-type patients. With ALR and CON cutoff of 2.10 and 1.95, the sensitivity and specificity to predict KCNJ5 mutation were 85%, 57% and 45%, 93%, respectively. Among 20 patients with KCNJ5 mutation, 16 showed G151R point mutation ( KCNJ5 - G151R) and 4 showed L168R point mutation ( KCNJ5 -L168R), which former one had significantly lower ALR (p=0.0471)., Conclusion: PA patients harboring somatic KCNJ5 mutation had significantly higher NP-59 uptake regarding to ALR and CON than those without mutation. APAs with KCNJ5- L168R point mutation showed significantly higher ALR than those with KCNJ5 -G151R point mutation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lu, Yen, Peng, Huang, Wu, Chueh and Lin.)
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- 2021
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33. Assessing tumor angiogenesis using dynamic contrast-enhanced integrated magnetic resonance-positron emission tomography in patients with non-small-cell lung cancer.
- Author
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Huang YS, Chen JL, Chen HM, Yeh LH, Shih JY, Yen RF, and Chang YC
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung mortality, Cohort Studies, Female, Humans, Lung Neoplasms mortality, Male, Middle Aged, Prospective Studies, Survival Analysis, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Lung Neoplasms diagnostic imaging, Magnetic Resonance Imaging methods, Positron-Emission Tomography methods, Precision Medicine methods, Tomography, X-Ray Computed methods
- Abstract
Background: Angiogenesis assessment is important for personalized therapeutic intervention in patients with non-small-cell lung cancer (NSCLC). This study investigated whether radiologic parameters obtained by dynamic contrast-enhanced (DCE)-integrated magnetic resonance-positron emission tomography (MR-PET) could be used to quantitatively assess tumor angiogenesis in NSCLC., Methods: This prospective cohort study included 75 patients with NSCLC who underwent DCE-integrated MR-PET at diagnosis. The following parameters were analyzed: metabolic tumor volume (MTV), maximum standardized uptake value (SUV
max ), reverse reflux rate constant (kep ), volume transfer constant (Ktrans ), blood plasma volume fraction (vp ), extracellular extravascular volume fraction (ve ), apparent diffusion coefficient (ADC), and initial area under the time-to-signal intensity curve at 60 s post enhancement (iAUC60 ). Serum biomarkers of tumor angiogenesis, including vascular endothelial growth factor-A (VEGF-A), angiogenin, and angiopoietin-1, were measured by enzyme-linked immunosorbent assays simultaneously., Results: Serum VEGF-A (p = 0.002), angiogenin (p = 0.023), and Ang-1 (p < 0.001) concentrations were significantly elevated in NSCLC patients compared with healthy individuals. MR-PET parameters, including MTV, Ktrans , and kep , showed strong linear correlations (p < 0.001) with serum angiogenesis-related biomarkers. Serum VEGF-A concentrations (p = 0.004), MTV values (p < 0.001), and kep values (p = 0.029) were significantly higher in patients with advanced-stage disease (stage III or IV) than in those with early-stage disease (stage I or II). Patients with initial higher values of angiogenesis-related MR-PET parameters, including MTV > 30 cm3 (p = 0.046), Ktrans > 200 10- 3 /min (p = 0.069), and kep > 900 10- 3 /min (p = 0.048), may have benefited from angiogenesis inhibitor therapy, which thus led to significantly longer overall survival., Conclusions: The present findings suggest that DCE-integrated MR-PET provides a reliable, non-invasive, quantitative assessment of tumor angiogenesis; can guide the use of angiogenesis inhibitors toward longer survival; and will play an important role in the personalized treatment of NSCLC.- Published
- 2021
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34. Integrated 18 F-T807 Tau PET, Structural MRI, and Plasma Tau in Tauopathy Neurodegenerative Disorders.
- Author
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Li CH, Chen TF, Chiu MJ, Yen RF, Shih MC, and Lin CH
- Abstract
Background and Objective: Tau-specific positron emission topography (PET) imaging enables in vivo assessment of Alzheimer's disease (AD). We aimed to investigate its performance in combination with plasma tau levels in patients with non-AD tauopathy. Methods: A total of 47 participants were enrolled, including 10 healthy controls, 16 with tauopathy parkinsonism syndromes (9 with corticobasal syndrome [CBS], 7 with progressive supranuclear palsy [PSP]), 9 with frontotemporal dementia (FTD), 4 with AD, and 8 with Parkinson's disease (PD). All participants underwent clinical assessments,
18 F-T807 tau PET, brain MRI, and plasma tau assay. Results: The global cortical standard uptake value ratio (SUVR) of18 F-T807 PET was comparable between PD and control ( p = 0.088). The cortical SUVR was significantly higher in AD group ( p = 0.002) but was modestly increased in PSP group compared to the PD group ( p = 0.044), especially in parietal and pallidal regions. Asymmetric18 F-T807 uptake at the pallidum was noted in patients with CBS and FTD. Cortical tau tracer uptake was associated with increased plasma total tau level ( p = 0.016), especially in frontal and parietal regions. Regional tracer uptake was correlated with cortical thinning in patients with CBS and PSP (CBS: r = -0.092, p = 0.025; PSP: r = -0.114, p = 0.015). Conclusions: The18 F-T807 tau tracer uptake was only modestly increased in patients with PSP. Although the cortical tau tracer uptake correlated with regional cortical atrophy and plasma tau levels, a four-repeated tau-specific tracer is needed for future classifying tauopathy parkinsonism syndromes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Chen, Chiu, Yen, Shih and Lin.)- Published
- 2021
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35. Endoscopic ultrasound ablation in a patient with multiple metastatic pancreatic tumors from adrenocorticotropic hormone-producing thymic neuroendocrine neoplasm.
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Chang LK, Chen KC, Cheng MF, Lin CC, Wang HP, Sung CT, Chen JH, Yen RF, Hsu CL, and Shih SR
- Subjects
- Adrenocorticotropic Hormone, Endosonography, Female, Humans, Middle Aged, Pancreas, Neuroendocrine Tumors diagnostic imaging, Neuroendocrine Tumors surgery, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms surgery
- Abstract
Adrenocorticotropic hormone (ACTH)-producing neuroendocrine neoplasm (NEN) of the thymus is rare. Lymph nodes and bones are the most common metastatic sites. Most cases present with florid Cushing's syndrome (CS). Here, we reported a 58-year-old woman, who presented with intermittent flush and weight loss. Imaging studies revealed tumors in the mediastinum, pancreas, and bones. Contrast-enhanced harmonic endoscopic ultrasound (EUS) of the pancreatic tumors showed heterogeneous and hyperenhancing characteristics. EUS elastography revealed a heterogeneous stiff pattern. EUS-fine needle biopsy to the pancreatic lesion confirmed the NEN nature. Serum ACTH and cortisol levels were abnormally high. Immunohistochemical staining of the thymic and pancreatic specimens was positive for ACTH. However, the patient did not have obvious CS appearance. The patient underwent surgery, radiation, EUS-guided ethanol injection, and anti-cancer medications, but the disease still progressed. The patient died from infection 16 months after NEN was diagnosed. In conclusion, the pancreas can be a metastatic site for ACTH-producing thymic NEN. EUS-associated procedures can help in the diagnosis and treatment of pancreatic metastatic NEN., (© 2020 Japan Gastroenterological Endoscopy Society.)
- Published
- 2021
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36. PET/MRI in Cervical Cancer: Associations Between Imaging Biomarkers and Tumor Stage, Disease Progression, and Overall Survival.
- Author
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Shih IL, Yen RF, Chen CA, Cheng WF, Chen BB, Chang YH, Cheng MF, and Shih TT
- Subjects
- Biomarkers, Disease Progression, Female, Humans, Magnetic Resonance Imaging, Positron-Emission Tomography, Prognosis, Prospective Studies, Radiopharmaceuticals, Retrospective Studies, Tumor Burden, Fluorodeoxyglucose F18, Uterine Cervical Neoplasms diagnostic imaging
- Abstract
Background: Positron emission tomography (PET)/MRI biomarkers have been shown to have prognostic significance in patients with cervical cancer. Their associations with progression-free survival (PFS) and overall survival (OS) merit further investigation., Purpose: To evaluate the association between PET/MRI biomarkers and tumor stage, PFS, and OS in patients with cervical cancer., Study Type: Prospective cohort study., Population: In all, 54 patients with newly diagnosed cervical cancer and measurable tumors (>1 cm) were included in the image analysis., Field Strength/sequence: 3.0T integrated PET/MRI including diffusion-weighted echo-planar imaging (b = 50 and 1000 s/mm
2 ) and [18F]fluorodeoxyglucose PET., Assessment: Two radiologists measured the minimum and mean apparent diffusion coefficient (ADCmin and ADCmean ), maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors., Statistical Tests: A Mann-Whitney U-test was used to evaluate the association between the imaging biomarkers and tumor stage. A Cox proportional hazards model was used to assess the relationships between the imaging biomarkers and survival., Results: In advanced tumors (T ≥ 1b2, M1, stage ≥ IB3), ADCmin was significantly lower and MTV, TLG, MTV/ADCmin , and TLG/ADCmin were significantly higher (P values between <0.001 and 0.036). In N1 tumors, ADCmin was significantly lower and MTV and MTV/ADCmin were significantly higher (P values between 0.005 and 0.016). In survival analysis, SUVmax was an independent predictor of PFS (hazard ratio [HR] = 4.57, P < 0.05), and ADCmin was an independent predictor of OS (HR = 0.02, P < 0.05). In subgroup analysis of patients with different stages, MTV/ADCmin was a predictor of PFS in stage I disease (P = 0.003), ADCmin (P = 0.038), and MTV (P = 0.020) in stage II, SUVmax (P = 0.006), and TLG (P = 0.006) in stage IV; and ADCmin was a predictor of OS in stage III disease (P = 0.008)., Data Conclusion: PET/MRI biomarkers of cervical cancer are associated with tumor stage and survival. SUVmax and ADCmin are independent predictors of PFS and OS, respectively., Level of Evidence: 1 TECHNICAL EFFICACY: 3., (© 2020 International Society for Magnetic Resonance in Medicine.)- Published
- 2021
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37. Synthesis and analysis of 4-(3-fluoropropyl)-glutamic acid stereoisomers to determine the stereochemical purity of (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) for clinical use.
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Shih KT, Huang YY, Yang CY, Cheng MF, Tien YW, Shiue CY, Yen RF, and Hsin LW
- Subjects
- Chromatography, High Pressure Liquid, Crystallization, Humans, Injections, Stereoisomerism, Glutamates chemical synthesis, Glutamates chemistry
- Abstract
(4S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid ([18F]FSPG) is a positron emission tomography (PET) imaging agent for measuring the system xC- transporter activity. It has been used for the detection of various cancers and metastasis in clinical trials. [18F]FSPG is also a promising diagnostic tool for evaluation of multiple sclerosis, drug resistance in chemotherapy, inflammatory brain diseases, and infectious lesions. Due to the very short half-life (110 min) of 18F nuclide, [18F]FSPG needs to be produced on a daily basis; therefore, fast and efficient synthesis and analytical methods for quality control must be established to assure the quality and safety of [18F]FSPG for clinical use. To manufacture cGMP-compliant [18F]FSPG, all four nonradioactive stereoisomers of FSPG were prepared as reference standards for analysis. (2S,4S)-1 and (2R,4R)-1 were synthesized starting from protected L- and D-glutamate derivatives in three steps, whereas (2S,4R)-1 and (2R,4S)-1 were prepared in three steps from protected (S)- and (R)-pyroglutamates. A chiral HPLC method for simultaneous determination of four FSPG stereoisomers was developed by using a 3-cm Chirex 3126 column and a MeCN/CuSO4(aq) mobile phase. In this method, (2R,4S)-1, (2S,4S)-1, (2R,4R)-1, and (2S,4R)-1 were eluted in sequence with sufficient resolution in less than 25 min without derivatization. Scale-up synthesis of intermediates for the production of [18F]FSPG in high optical purity was achieved via stereo-selective synthesis or resolution by recrystallization. The enantiomeric excess of intermediates was determined by HPLC using a Chiralcel OD column and monitored at 220 nm. The nonradioactive precursor with >98% ee can be readily distributed to other facilities for the production of [18F]FSPG. Based on the above accomplishments, cGMP-compliant [18F]FSPG met the acceptance criteria in specifications and was successfully manufactured for human use. It has been routinely prepared and used in several pancreatic ductal adenocarcinoma metastasis-related clinical trials., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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38. Mitochondrial UQCRC1 mutations cause autosomal dominant parkinsonism with polyneuropathy.
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Lin CH, Tsai PI, Lin HY, Hattori N, Funayama M, Jeon B, Sato K, Abe K, Mukai Y, Takahashi Y, Li Y, Nishioka K, Yoshino H, Daida K, Chen ML, Cheng J, Huang CY, Tzeng SR, Wu YS, Lai HJ, Tsai HH, Yen RF, Lee NC, Lo WC, Hung YC, Chan CC, Ke YC, Chao CC, Hsieh ST, Farrer M, and Wu RM
- Subjects
- Age of Onset, Aged, Animals, Antiparkinson Agents therapeutic use, Cell Line, Chromosome Aberrations, Drosophila, Electron Transport Complex III genetics, Female, Frameshift Mutation, Gene Knock-In Techniques, Genes, Dominant, Humans, Levodopa therapeutic use, Male, Mice, Middle Aged, Mutation genetics, Parkinsonian Disorders complications, Parkinsonian Disorders drug therapy, Pedigree, Polyneuropathies etiology, Exome Sequencing, Mitochondria genetics, Parkinsonian Disorders genetics, Polyneuropathies genetics
- Abstract
Parkinson's disease is a neurodegenerative disorder with a multifactorial aetiology. Nevertheless, the genetic predisposition in many families with multi-incidence disease remains unknown. This study aimed to identify novel genes that cause familial Parkinson's disease. Whole exome sequencing was performed in three affected members of the index family with a late-onset autosomal-dominant parkinsonism and polyneuropathy. We identified a novel heterozygous substitution c.941A>C (p.Tyr314Ser) in the mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) gene, which co-segregates with disease within the family. Additional analysis of 699 unrelated Parkinson's disease probands with autosomal-dominant Parkinson's disease and 1934 patients with sporadic Parkinson's disease revealed another two variants in UQCRC1 in the probands with familial Parkinson's disease, c.931A>C (p.Ile311Leu) and an allele with concomitant splicing mutation (c.70-1G>A) and a frameshift insertion (c.73_74insG, p.Ala25Glyfs*27). All substitutions were absent in 1077 controls and the Taiwan Biobank exome database from healthy participants (n = 1517 exomes). We then assayed the pathogenicity of the identified rare variants using CRISPR/Cas9-based knock-in human dopaminergic SH-SY5Y cell lines, Drosophila and mouse models. Mutant UQCRC1 expression leads to neurite degeneration and mitochondrial respiratory chain dysfunction in SH-SY5Y cells. UQCRC1 p.Tyr314Ser knock-in Drosophila and mouse models exhibit age-dependent locomotor defects, dopaminergic neuronal loss, peripheral neuropathy, impaired respiratory chain complex III activity and aberrant mitochondrial ultrastructures in nigral neurons. Furthermore, intraperitoneal injection of levodopa could significantly improve the motor dysfunction in UQCRC1 p.Tyr314Ser mutant knock-in mice. Taken together, our in vitro and in vivo studies support the functional pathogenicity of rare UQCRC1 variants in familial parkinsonism. Our findings expand an additional link of mitochondrial complex III dysfunction in Parkinson's disease., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2020
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39. Three-step two-pot automated production of NCA [ 18 F]FDOPA with FlexLab module.
- Author
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Huang YY, Poniger S, Tsai CL, Tochon-Danguy HJ, Ackermann U, and Yen RF
- Abstract
Automated three-step two-pot production of no-carrier-added (NCA) [
18 F]FDOPA was first implemented in the iPHASE FlexLab module. Decay-corrected radiochemical yield (RCY) of [18 F]FDOPA synthesized by this method was 10~14% (n = 7) with a synthesis time of ~110 min [18 F]FDOPA was obtained in > 95% of radiochemical purity with a molar activity of ~431 GBq/μmol. With the method successfully implementing on the commercial FlexLab module and its built-in step-by-step activity monitoring, further processes optimization would be achieved., (Copyright © 2019. Published by Elsevier Ltd.)- Published
- 2020
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40. Dermoid cyst with secretion of CA 19-9 detected by 18F-FDG PET/CT: A case report.
- Author
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Lin SC, Yen RF, and Chen YK
- Subjects
- Adult, Biomarkers, Tumor blood, Dermoid Cyst blood, Dermoid Cyst diagnostic imaging, Dermoid Cyst surgery, Diagnosis, Differential, Female, Fluorodeoxyglucose F18, Humans, Ovarian Cysts blood, Ovarian Cysts diagnostic imaging, Ovarian Cysts surgery, Ovariectomy, Positron Emission Tomography Computed Tomography, Radiopharmaceuticals, CA-19-9 Antigen blood, Dermoid Cyst diagnosis, Ovarian Cysts diagnosis
- Abstract
Introduction: Carbohydrate antigen 19-9 (CA 19-9) is a tumor glycolipid, frequently elevated in the serum of patients due to malignancies from gastrointestinal organs; in particular, the pancreas. This carbohydrate antigen is also expressed in benign diseases., Patient Concerns: A case of a 27-year-old female who has an unknown origin CA 19-9 elevation for 2 years., Diagnosis: After the left ovarian cystectomy and microscopic examination, the final diagnosis is a dermoid cyst. The dermoid cyst shows increased F-fluorodeoxyglucose (F-FDG) uptake in the F-FDG positron emission tomography (PET)/computed tomography (CT) study., Intervention and Outcomes: The laparoscopic oophorocystectomy was performed. It was observed that the patient's CA 19-9 level returned to normal after the surgery 6 months later. This showed that the dermoid cyst was responsible for the abnormal CA 19-9 level., Conclusion: In this case, we can learn that the F-FDG PET/CT scan has potential use in patients with unknown origin of elevation CA 19-9.
- Published
- 2020
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41. Frontal variant of Alzheimer's disease with asymmetric presentation mimicking frontotemporal dementia: Case report and literature review.
- Author
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Li CH, Fan SP, Chen TF, Chiu MJ, Yen RF, and Lin CH
- Subjects
- Aged, Alzheimer Disease diagnostic imaging, Alzheimer Disease metabolism, Amyloid beta-Peptides metabolism, Biomarkers metabolism, Diagnosis, Differential, Executive Function physiology, Frontotemporal Dementia diagnostic imaging, Frontotemporal Dementia metabolism, Humans, Male, Middle Aged, Neuroimaging, Neuropsychological Tests, Phosphorylation, Positron-Emission Tomography methods, tau Proteins metabolism, Alzheimer Disease diagnosis, Brain diagnostic imaging, Frontotemporal Dementia diagnosis
- Abstract
Introduction: Frontal variant of Alzheimer's disease (fvAD) is a rare nonamnestic syndrome of Alzheimer's disease (AD). Differentiating it from behavior variant of frontotemporal dementia (bvFTD), which has implications for treatment responses and prognosis, remains a clinical challenge., Methods: Molecular neuroimaging and biofluid markers were performed for the index patient for accurate premortem diagnosis of fvAD. The clinical, neuroimaging, and biofluid characteristics of the patient were compared to those reported in previous studies of fvAD from 1999 to 2019., Results: A 66-year-old man presented with progressive executive dysfunction, personality and behavioral changes, and memory decline since age 59. He had no family history of neurodegenerative disorders. A stimulus-sensitive myoclonus was noted over his left upper extremity. Neuropsychological assessment revealed moderate dementia with a Mini-Mental State Exam score of 10/30 and compromised executive and memory performance. Brain imaging showed asymmetrical atrophy and hypometabolism over the right frontal and temporal areas, mimicking bvFTD. However, we observed increased tau depositions based on
18 F-labeled T807 Tau PET in these areas and diffusely increased amyloid deposition based on11 C-labeled Pittsburgh compound B positron emission tomography (PET). Plasma biomarker measures indicated an AD profile with increased Aβ1-42 (18.66 pg/ml; cutoff: 16.42 pg/ml), Aβ1-42/Aβ1-40 ratio (0.45; cutoff: 0.30), total tau (29.78 pg/ml; cutoff: 23.89 pg/ml), and phosphorylated tau (4.11 pg/ml; cutoff: 3.08 pg/ml). These results supported a diagnosis of fvAD., Conclusions: Our results with asymmetrical presentations extend current knowledge about this rare AD variant. Application of biofluid and molecular imaging markers could assist in early, accurate diagnosis., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)- Published
- 2020
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42. Clinical significance of quantitative assessment of glucose utilization in patients with ischemic cardiomyopathy.
- Author
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Ko KY, Wang SY, Yen RF, Shiau YC, Hsu JC, Tsai HY, Lee CL, Chiu KM, and Wu YW
- Subjects
- Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Humans, Male, Middle Aged, Positron-Emission Tomography, Tomography, Emission-Computed, Single-Photon, Fluorodeoxyglucose F18 pharmacokinetics, Glucose metabolism, Myocardial Ischemia diagnostic imaging, Myocardial Ischemia metabolism, Myocardium metabolism, Radiopharmaceuticals pharmacokinetics
- Abstract
Background: The aim of this study was to prospectively quantify the rate of myocardial glucose uptake (MRGlu) in myocardium with different perfusion-metabolism patterns and determine its prognostic value in patients with ischemic cardiomyopathy., Methods and Results: 79 patients with ischemic cardiomyopathy were prospectively enrolled for dynamic cardiac FDG PET, and then followed for at least 6 months. Perfusion-metabolism patterns were determined based on visual score analysis of
201 Tl SPECT and FDG PET. MRGlu was analyzed using the Patlak kinetic model. The primary end-point was cardiovascular mortality. Significantly higher MRGlu was observed in viable compared with non-viable areas. Negative correlations were found between MRGlu in transmural match and a history of hyperlipidemia, statin usage, and triglyceride levels. Diabetic patients receiving dipeptidyl peptidase-4 inhibitors (DPP4i) had a significantly lower MRGlu in transmural match, mismatch, and reverse mismatch. Patients with MRGlu in transmural match ≥ 23.40 or reverse mismatch ≥ 36.90 had a worse outcome., Conclusions: Myocardial glucose utilization was influenced by substrates and medications, including statins and DPP4i. MRGlu could discriminate between viable and non-viable myocardium, and MRGlu in transmural match and reverse mismatch may be prognostic predictors of cardiovascular death in patients with ischemic cardiomyopathy.- Published
- 2020
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43. Superficial Cerebellar Microbleeds and Cerebral Amyloid Angiopathy: A Magnetic Resonance Imaging/Positron Emission Tomography Study.
- Author
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Tsai HH, Pasi M, Tsai LK, Chen YF, Chen YW, Tang SC, Gurol ME, Yen RF, and Jeng JS
- Subjects
- Aged, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Cerebral Amyloid Angiopathy diagnostic imaging, Cerebral Hemorrhage diagnostic imaging, Magnetic Resonance Angiography, Positron-Emission Tomography
- Abstract
Background and Purpose- The differentiation between cerebral amyloid angiopathy (CAA) and hypertensive small vessel disease in primary intracerebral hemorrhage is mainly based on hemorrhagic neuroimaging markers in the supratentorial regions, and the cause for cerebellar microbleeds remains unknown. Our aim was to investigate whether superficial cerebellar microbleeds are more likely to be related to CAA rather than hypertensive small vessel disease. Methods- Two hundred seventy-five consecutive patients with intracerebral hemorrhage were retrospectively reviewed from a prospectively maintained hospital-based stroke registry. Eighty-five (33.1%) patients had cerebellar microbleeds and were categorized into superficial (gray matter, vermis), deep (white matter, deep nucleus, cerebellar peduncle), or mixed type based on the location of cerebellar hemorrhagic lesions. Amyloid imaging was obtained using 11C-Pittsburgh Compound B-positron emission tomography in a subgroup of patients. The associations between cerebellar microbleed locations and the type of small vessel disease (CAA versus hypertensive small vessel disease) based on distribution of supratentorial hemorrhagic lesions as well as other magnetic resonance imaging and positron emission tomography markers were analyzed. Results- The presence of cerebellar microbleed was independently associated with supratentorial microbleed and lacunar infarcts (both P <0.01). Strictly superficial cerebellar microbleeds were significantly related to CAA-intracerebral hemorrhage, cortical superficial siderosis and high-grade enlarged perivascular space in centrum semiovale (all P <0.05); deep or mixed cerebellar microbleeds were related to hypertension and deep microbleed (all P <0.05). In multivariable models, superficial cerebellar microbleeds were independently associated with CAA-intracerebral hemorrhage ( P =0.03). Of 33 patients assessed by amyloid positron emission tomography, cerebral and cerebellar amyloid load (standardized uptake value ratio) was higher in patients with superficial cerebellar microbleeds compared with deep/mixed cerebellar microbleeds (cerebrum standardized uptake value ratio [reference: cerebellum] 1.33±0.24 versus 1.05±0.09, P <0.001; cerebellum standardized uptake value ratio [reference: pons] 0.58±0.08 versus 0.51±0.09, P =0.03). Conclusions- Patients with strictly superficial cerebellar microbleeds are associated with a clinicoradiological diagnosis of CAA as well as increased cerebral and cerebellar amyloid deposition on Pittsburgh Compound B-positron emission tomography, suggesting underlying CAA pathology.
- Published
- 2020
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44. Improved diagnostic accuracy of thallium-201 myocardial perfusion single-photon emission computed tomography with CT attenuation correction.
- Author
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Huang JY, Yen RF, Lee WC, Huang CK, Hsu PY, Cheng MF, Lu CC, Lin YH, Chien KL, and Wu YW
- Subjects
- Aged, Area Under Curve, Coronary Angiography, Coronary Artery Disease diagnostic imaging, Coronary Vessels diagnostic imaging, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Obesity complications, ROC Curve, Reference Standards, Reproducibility of Results, Retrospective Studies, Sensitivity and Specificity, Sex Factors, Myocardial Perfusion Imaging, Single Photon Emission Computed Tomography Computed Tomography, Thallium Radioisotopes chemistry
- Abstract
Background: The benefits of attenuation correction (AC) in technetium-99m myocardial perfusion imaging (MPI) have been well established. However, the value of thallium (Tl-201) AC and routine computed tomography AC (CTAC) were less well established. The aims of this study were to evaluate the diagnostic performance of thallium (Tl-201) MPI with additional CTAC and to determine which participants would benefit most., Methods and Results: A total of 108 consecutive patients who underwent Tl-201 MPI and received coronary angiography within 3 months were enrolled. Diagnostic performance was determined by sensitivity, specificity, and receiver operating characteristic curve analysis. Subgroup analyses were performed using gender and obesity. CTAC improved the area under the curve (0.84 vs. 0.77, P = 0.037 at patient level), primarily due to a significant improvement in specificity (0.78 vs. 0.57, P = 0.013) and no significant difference in sensitivity (0.79 vs. 0.82, P = 0.75). In subgroup analysis, CTAC was most helpful in obese subjects, men, and especially right coronary artery lesions., Conclusions: CTAC significantly improved diagnostic performance primarily by increasing the specificity, and the improvements were significantly greater in obese patients and male patients. These findings suggest that CTAC should be applied to Tl-201 MPI as routine clinical practice.
- Published
- 2019
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45. Predicting tumor responses and patient survival in chemoradiotherapy-treated patients with non-small-cell lung cancer using dynamic contrast-enhanced integrated magnetic resonance-positron-emission tomography.
- Author
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Huang YS, Chen JL, Chen JY, Lee YF, Huang JY, Kuo SH, Yen RF, and Chang YC
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Contrast Media, Female, Humans, Lung Neoplasms mortality, Lung Neoplasms pathology, Male, Middle Aged, Neoplasm Staging, Predictive Value of Tests, Prognosis, Prospective Studies, Survival Rate, Treatment Outcome, Tumor Burden drug effects, Tumor Burden radiation effects, Carcinoma, Non-Small-Cell Lung therapy, Chemoradiotherapy methods, Image Enhancement, Lung Neoplasms diagnostic imaging, Lung Neoplasms therapy, Magnetic Resonance Imaging methods, Positron-Emission Tomography methods
- Abstract
Purpose: We investigated whether radiologic parameters by dynamic contrast-enhanced (DCE) integrated magnetic resonance-positron-emission tomography (MR-PET) predicts tumor response to treatment and survival in non-metastatic non-small-cell lung cancer (NSCLC) patients receiving chemoradiotherapy (CRT)., Methods: Patients underwent DCE integrated MR-PET imaging 1 week before CRT. The following parameters were analyzed: primary tumor size, gross tumor volume, maximal standardized uptake value (SUV
max ), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC), volume transfer constant (Ktrans ), reverse reflux rate constant (kep ), extracellular extravascular volume fraction (ve ), blood plasma volume fraction (vp ), and initial area under the time-concentration curve defined over the first 60 s post-enhancement (iAUC60 ). CRT responses were defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)., Results: Thirty patients were included. Non-responders demonstrated higher baseline TLG (p = 0.012), and lower baseline Ktrans (p = 0.020) and iAUC60 (p = 0.016) compared to responders, indicating the usefulness of DCE integrated MR-PET to predict treatment responses. Receiver operating characteristic curve indicated that TLG has the best differentiation capability to predict responders. By setting the threshold of TLG to 277, the sensitivity, specificity, and accuracy were 66.7%, 83.3%, and 75.0%, respectively, with an area under the curve of 0.776. The median follow-up time was 19.6 (range 7.8-32.0) months. In univariate analyses, baseline TLG >277 (p = 0.005) and baseline Kt rans <254 (10-3 min-1 ; p = 0.015) correlated with poor survival after CRT. In multivariate analysis, baseline TLG >277 remained the significant factor in predicting progression (p = 0.012) and death (p = 0.031)., Conclusions: The radiologic parameters derived from DCE integrated MR-PET scans are useful for predicting treatment response in NSCLC patients treated with CRT; furthermore, these parameters are correlated with clinical and survival outcomes including tumor progression and death.- Published
- 2019
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46. An one-pot two-step automated synthesis of [18F]T807 injection, its biodistribution in mice and monkeys, and a preliminary study in humans.
- Author
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Huang YY, Chiu MJ, Yen RF, Tsai CL, Hsieh HY, Chiu CH, Wu CH, Hsin LW, Tzen KY, Cheng CY, Ma KH, and Shiue CY
- Subjects
- Alzheimer Disease genetics, Alzheimer Disease pathology, Animals, Biological Availability, Carbolines blood, Carbolines pharmacokinetics, Contrast Media pharmacokinetics, Drug Evaluation, Preclinical, Gene Expression, Haplorhini, Humans, Injections, Intravenous, Macaca, Male, Mice, Mice, Inbred ICR, Middle Aged, Positron-Emission Tomography methods, Radiometry, Radiopharmaceuticals blood, Radiopharmaceuticals pharmacokinetics, Tissue Distribution, tau Proteins genetics, Alzheimer Disease diagnostic imaging, Carbolines chemical synthesis, Contrast Media chemical synthesis, Radiopharmaceuticals chemical synthesis, tau Proteins chemistry
- Abstract
[18F]T807 is a potent tau protein imaging agent. In order to fulfill the demand from preclinical and clinical studies, we developed an automated one-pot two-step synthesis of this potent tau imaging agent and studied its stability, and dosimetry in mice and monkeys. We also conducted a preliminary study of this imaging agent in humans. Using this one-pot two-step method, the radiochemical yield (RCY) of [18F]T807 was 20.5 ± 6.1% (n = 15) at the end of bombardment (EOB) in a synthesis time of 70±5 min. The chemical and radiochemical purities were >90% and the specific activities were 151 ± 52 GBq/μmol. The quality of [18F]T807 synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]T807 injection was stable at room temperature for up to 4 h after the end of synthesis (EOS). The estimated effective dose of the [18F]T807 injection extrapolated from monkeys was 19 μSv/MBq (n = 2), while the estimated effective doses of the [18F]T807 injection extrapolated from fasted and non-fasted mice were 123 ± 27 (n = 3) and 94 ± 19 (n = 4) μSv/MBq, respectively. This one-pot two-step automated method produced the [18F]T807 injection with high reproducibility and high quality. PET imaging and radiation dosimetry evaluation in mice and Formosan rock monkeys suggested that the [18F]T807 injection synthesized by this method is suitable for use in human PET imaging studies. Thus, this method could fulfill the demand for the [18F]T807 injection in both preclinical and clinical studies of tauopathies, especially for nearby study sites without cyclotrons., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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47. Advances in cerebral amyloid angiopathy imaging.
- Author
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Chen SJ, Tsai HH, Tsai LK, Tang SC, Lee BC, Liu HM, Yen RF, and Jeng JS
- Abstract
Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease caused by β -amyloid (Aβ) deposition at the leptomeningeal vessel walls. It is a common cause of spontaneous intracerebral hemorrhage and a frequent comorbidity in Alzheimer's disease. The high recurrent hemorrhage rate in CAA makes it very important to recognize this disease to avoid potential harmful medication. Imaging studies play an important role in diagnosis and research of CAA. Conventional computed tomography and magnetic resonance imaging (MRI) methods reveal anatomical alterations, and remains as the most reliable tool in identifying CAA according to modified Boston criteria. The vascular injuries of CAA result in both hemorrhagic and ischemic manifestations and related structural changes on MRI, including cerebral microbleeds, cortical superficial siderosis, white matter hyperintensity, MRI-visible perivascular spaces, and cortical microinfarcts. As imaging techniques advance, not only does the resolution of conventional imaging improve, but novel skills in functional and molecular imaging studies also enable in vivo analysis of vessel physiological changes and underlying pathology. These modern tools help in early detection of CAA and may potentially serve as sensitive outcome markers in future clinical trials. In this article, we reviewed past studies of CAA focusing on utilization of various conventional and novel imaging techniques in both research and clinical aspects., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.
- Published
- 2019
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48. Prospective comparison of (4S)-4-(3- 18 F-fluoropropyl)-L-glutamate versus 18 F-fluorodeoxyglucose PET/CT for detecting metastases from pancreatic ductal adenocarcinoma: a proof-of-concept study.
- Author
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Cheng MF, Huang YY, Ho BY, Kuo TC, Hsin LW, Shiue CY, Kuo HC, Jeng YM, Yen RF, and Tien YW
- Subjects
- Cell Line, Tumor, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Positron Emission Tomography Computed Tomography adverse effects, Prospective Studies, Safety, Adenocarcinoma diagnostic imaging, Adenocarcinoma pathology, Fluorodeoxyglucose F18, Glutamates, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms pathology, Positron Emission Tomography Computed Tomography methods
- Abstract
Purpose: (4S)-4-(3-
18 F-Fluoropropyl)-L-glutamate (FSPG) positron emission tomography (PET) reflects system xC - transporter (xCT) expression. FSPG PET has been used to detect brain, lung, breast and liver cancer with only modest success. There is no report on the use of FSPG PET in pancreatic ductal adenocarcinoma (PDAC), presumably because of normal xCT expression in the pancreas. Nonetheless, the tissue-specific expression of xCT in the pancreas suggests that FSPG PET may be ideal for identifying metastasized PDAC., Methods: The performance of FSPG in detecting PDAC metastases was compared with that of18 F-fluorodeoxyglucose (FDG) in small-animal PET studies in seven PDAC tumour-bearing mice and in prospective PET/computed tomography (CT) studies in 23 patients with tissue-confirmed PDAC of stage III or stage IV. All PET/CT results were correlated with the results of histopathology or contrast-enhanced CT (ceCT) performed 3 and 6 months later., Results: In the rodent model, FSPG PET consistently found more PDAC metastases earlier than FDG PET. FSPG PET showed a trend for a higher sensitivity, specificity and diagnostic accuracy than FDG PET in detecting PDAC metastases in a patient-based analysis: 95.0%, 100.0% and 95.7%, and 90.0%, 66.7% and 90.0%, respectively. In a lesion-based analysis, FSPG PET identified significantly more PDAC metastases, especially in the liver, than FDG PET (109 vs. 95; P = 0.0001, 95% CI 4.9-14.6). The tumour-to-background ratios for FSPG and FDG uptake on positive scans were similar (FSPG 4.2 ± 4.3, FDG 3.6 ± 3.0; P = 0.44, 95% CI -1.11 to 0.48), despite a lower tumour maximum standardized uptake value in FSPG-avid lesions (FSPG 4.2 + 2.3, FDG 7.7 + 5.7; P = 0.002, 95% CI 0.70-4.10). Because of the lower physiological activity of FSPG in the liver, FSPG PET images of the liver are more easy to interpret than FDG PET images, and therefore the use of FSPG improves the detection of liver metastasis., Conclusion: FSPG PET is superior to FDG PET in detecting metastasized PDAC, especially in the liver.- Published
- 2019
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49. Microangiopathy underlying mixed-location intracerebral hemorrhages/microbleeds: A PiB-PET study.
- Author
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Tsai HH, Pasi M, Tsai LK, Chen YF, Lee BC, Tang SC, Fotiadis P, Huang CY, Yen RF, Jeng JS, and Gurol ME
- Subjects
- Aged, Aged, 80 and over, Aniline Compounds, Cerebral Amyloid Angiopathy complications, Cerebral Hemorrhage etiology, Cerebral Small Vessel Diseases complications, Cross-Sectional Studies, Female, Humans, Intracranial Hemorrhage, Hypertensive diagnostic imaging, Intracranial Hemorrhage, Hypertensive etiology, Magnetic Resonance Imaging, Male, Middle Aged, Positron-Emission Tomography, Taiwan, Thiazoles, Brain diagnostic imaging, Cerebral Amyloid Angiopathy diagnostic imaging, Cerebral Hemorrhage diagnostic imaging, Cerebral Small Vessel Diseases diagnostic imaging
- Abstract
Objective: To test the hypothesis that patients with concomitant lobar and deep intracerebral hemorrhages/microbleeds (mixed ICH) have predominantly hypertensive small vessel disease (HTN-SVD) rather than cerebral amyloid angiopathy (CAA), using in vivo amyloid imaging., Methods: Eighty Asian patients with primary ICH without dementia were included in this cross-sectional study. All patients underwent brain MRI and
11 C-Pittsburgh compound B (PiB)-PET imaging. The mean cortical standardized uptake value ratio (SUVR) was calculated using cerebellum as reference. Forty-six patients (57.5%) had mixed ICH. Their demographic and clinical profile as well as amyloid deposition patterns were compared to those of 13 patients with CAA-ICH and 21 patients with strictly deep microbleeds and ICH (HTN-ICH)., Results: Patients with mixed ICH were younger (62.8 ± 11.7 vs 73.3 ± 11.9 years in CAA, p = 0.006) and showed a higher rate of hypertension than patients with CAA-ICH ( p < 0.001). Patients with mixed ICH had lower PiB SUVR than patients with CAA (1.06 [1.01-1.13] vs 1.43 [1.06-1.58], p = 0.003). In a multivariable logistic regression model, mixed ICH was associated with hypertension (odds ratio 8.9, 95% confidence interval 1.4-58.4, p = 0.02) and lower PiB SUVR (odds ratio 0.03, 95% confidence interval 0.001-0.87, p = 0.04) compared to CAA after adjustment for age. Compared to HTN-ICH, mixed ICH showed a similar mean age (62.8 ± 11.7 vs 60.1 ± 14.5 years in HTN-ICH) and risk factor profile (all p > 0.1). Furthermore, PiB SUVR did not differ between mixed ICH (values presented above) and HTN-ICH (1.10 [1.00-1.16], p = 0.45)., Conclusions: Patients with mixed ICH have much lower amyloid load than patients with CAA-ICH, while being similar to HTN-ICH. Overall, mixed ICH is probably caused by HTN-SVD, an important finding with clinical relevance., (© 2019 American Academy of Neurology.)- Published
- 2019
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50. Multiparametric PET/MR imaging biomarkers are associated with overall survival in patients with pancreatic cancer.
- Author
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Chen BB, Tien YW, Chang MC, Cheng MF, Chang YT, Yang SH, Wu CH, Kuo TC, Shih IL, Yen RF, and Shih TT
- Subjects
- Aged, Biomarkers, Female, Fluorodeoxyglucose F18, Humans, Male, Middle Aged, Pancreatic Neoplasms mortality, Prognosis, Prospective Studies, Radiopharmaceuticals, Retrospective Studies, Tumor Burden, Magnetic Resonance Imaging, Pancreatic Neoplasms diagnostic imaging, Positron-Emission Tomography
- Abstract
Purpose: To correlate the overall survival (OS) with the imaging biomarkers of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy, and glucose metabolic activity derived from integrated fluorine 18 fluorodeoxyglucose positron emission tomography (
18 F-FDG PET)/MRI in patients with pancreatic cancer., Methods: This prospective study was approved by the institutional review board and informed consent was obtained from all participants. Sixty-three consecutive patients (mean age, 62.7 ± 12 y; men/women, 40/23) with pancreatic cancer underwent PET/MRI before treatment. The imaging biomarkers were comprised of DCE-MRI parameters (peak, IAUC60 , Ktrans , kep , ve ), the minimum apparent diffusion coefficient (ADCmin ), choline level, standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) of the tumors. The relationships between these imaging biomarkers with OS were evaluated with the Kaplan-Meier and Cox proportional hazard models., Results: Seventeen (27%) patients received curative surgery, with the median follow-up duration being 638 days. Univariate analysis showed that patients at a low TNM stage (≦3, P = 0.041), high peak (P = 0.006), high ADCmin (P = 0.002) and low TLG (P = 0.01) had better OS. Moreover, high TLG/peak ratio was associated with poor OS (P = 0.016). Multivariate analysis indicated that ADCmin (P = 0.011) and TLG/peak ratio (P = 0.006) were independent predictors of OS after adjustment for age, gender, tumor size, and TNM stage. The TLG/peak ratio was an independent predictor of OS in a subgroup of patients who did not receive curative surgery (P = 0.013)., Conclusion: The flow-metabolism mismatch reflected by the TLG/peak ratio may better predict OS than other imaging biomarkers from PET/MRI in pancreatic cancer patients.- Published
- 2018
- Full Text
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