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Objective: The current study aimed to investigate the basic principles and clinical applications, including the selection of proper candidates, follow-up strategies, and radiation protection issues relating to peptide receptor radionuclide therapy (PRRT). Data Sources and Study Selection: We searched various scientific databases using specific keywords. Results: Due to the overexpression of somatostatin receptors in neuroendocrine tumors (NETs), PRRT is currently considered an important therapeutic modality for the management of NETs. Conclusion: PRRT incorporates the systemic administration of a tumor-targeting radiolabeled peptide to patients with tumors, allowing for more precise delivery of radiation doses to tumor sites while sparing normal tissues.

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

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

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.

Abstract Purpose We compared hypermetabolic lymphadenopathy (HLN) on 18F-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.

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.

The aim of this study was to update the information on internationally acceptable standards and clinical practice recommendations for the management of patients with primary aldosteronism (PA). The Taiwan Society of Aldosteronism (TSA) Task Force acknowledged the novel issues of PA and reached a group consensus on PA in Taiwan by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. Unilateral adrenalectomy is the preferred treatment for patients with aldosterone-producing adenoma (APA). For medical treatment with mineralocorticoid receptor antagonists (MRAs), spironolactone is the first-line treatment, and eplerenone is a reasonable alternative in PA patients intolerant or contraindicated to spironolactone. The dose of MRAs can be titrated according to plasma renin activity (PRA). For screening PA-related comorbidities, we suggest albuminuria to predict a post-treatment decline in renal function, echocardiography as cardiac evaluation, bone mineral density scan for osteoporosis, and obstructive sleep apnea. In tissue and genetic surveys, we suggest immunohistochemical staining and somatic mutation screening for post-operative adrenal specimens in APA patients. With this consensus, we hope to update the information on PA for clinical physicians to facilitate better identification, management and treatment of patients with PA.

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 (SUVmax), reverse reflux rate constant (k ep), volume transfer constant (K trans), blood plasma volume fraction (v p ), extracellular extravascular volume fraction (v e ), 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 30 cm3 (p = 0.046), K trans > 200 10− 3/min (p = 0.069), and k ep > 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.

Background. [18F]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 [18F]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/μmol (EOS, n=15), respectively. The quality of the [18F]FEPPA synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]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 [18F]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, [18F]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.

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.

Background/Purpose: Even with the increasing recognition of primary aldosteronism (PA) as a cause of refractory hypertension and an issue of public health, the consensus of its optimal surgical or medical treatment in Taiwan has not been reached. Our objective was to develop a clinical practice guideline that is feasible for real-world management of PA patients in Taiwan. Methods: The Taiwan Society of Aldosteronism (TSA) Task Force recognized the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics and constraints into PA management. Results: In patients with lateralized PA, including aldosterone producing adenoma (APA), laparoscopic adrenalectomy is the ‘gold standard’ of treatment. Mini-laparoscopic and laparoendoscopic single-site approaches are feasible only in highly experienced surgeons. Patients with bilateral adrenal hyperplasia or those not suitable for surgery should be treated by mineralocorticoid receptor antagonists. The outcome data of PA patient management from the literature, especially from PA patients in Taiwan, are reviewed. Mental health screening is helpful in early detection and management of psychopathology among PA patients. Conclusion: We hope this consensus will provide a guideline to help medical professionals to manage PA patients in Taiwan to achieve a better quality of care. Keywords: Primary aldosteronism, Guideline, TAIPAI

PurposeSomatic 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.MethodsSixty-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.ResultsTwenty 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).ConclusionPA 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.

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, 18F-T807 tau PET, brain MRI, and plasma tau assay.Results: The global cortical standard uptake value ratio (SUVR) of 18F-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. Asymmetric 18F-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: The 18F-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.

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.

Introduction Primary aldosteronism (PA) is a common form of secondary hypertension that has significant cardiovascular events and increased prevalence of metabolic syndrome and diabetics. Although plasma aldosterone concentration is positively correlated with visceral fat area (VFA) in non-PA individuals, the role of visceral adiposity associated with clinical success after surgery is not known.Research design and methods We analyzed patients who underwent adrenalectomy for aldosterone-producing adenoma (APA) at the Taiwan PA Investigator group. VFA was calculated from the abdominal CT scan at APA diagnosis, and all patients received adrenalectomy.Results The study involved 100 consecutive patients with APA (42 males; mean age 49.3 years) matched with 41 essential hypertension (EH) patients. Patients with APA had smaller VFA (p=0.010) than their EH counterparts. Multiple linear regression analysis revealed that the duration of hypertension (p=0.007), but not plasma aldosterone, was negatively correlated with VFA in patients with APA. Logistic regression analysis showed that log VFA (OR=0.065, p

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 18F‐labeled T807 Tau PET in these areas and diffusely increased amyloid deposition based on 11C‐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.

Objectives: Adrenocortical scintigraphy for patients with primary aldosteronism (PA) without discontinuation or modification of antihypertensive medications is of concern because of drug interference with the renin–angiotensin–aldosterone system. We report the surgical outcomes of patients with PA lateralized with adrenocortical scintigraphy without drug discontinuation or modification. Materials and Methods: We retrospectively reviewed 34 patients with PA with computed tomography (CT)-documented adrenal tumors who had undergoing subsequent I-131-6 β-iodomethyl-norcholesterol (NP-59) single photon emission CT (SPECT)/CT followed by unilateral adrenalectomy according to the results of NP-59 uptake between May 2005 and December 2014. All enrolled patients underwent standard confirmatory tests and lateralization with NP-59 SPECT/CT without discontinuation of existing antihypertensive medications, including spironolactone. The pathological findings, hypertension outcomes, and biochemical changes were reported. The accuracy of NP-59 SPECT/CT without drug discontinuation or modification was also evaluated. Results: None of the 34 enrolled patients (M:F = 16:18) had complications such as a hypertensive crisis, life-threatening hypokalemic event, or cardiac arrhythmia. Pathology disclosed 31 (91%) adenomas and three cases of hyperplasia. Hypertension cure and improvement were observed in 12 (35%) and 18 (53%) patients, respectively. All of the 30 patients (100%) without postoperative use of beta-blockers and with an available postoperative aldosterone/renin ratio achieved a biochemical cure. The positive predictive values of NP-59 SPECT/CT were 91%, 88%, and 100% for the pathological findings, hypertension outcomes, and biochemical changes, respectively. Conclusion: Noninvasive NP-59 SPECT/CT without discontinuation or modification of antihypertensive medications not only provided accurate lateralization and safety but also resulted in a high improvement rate for PA-associated hypertension.

Background/Purpose: Even though the increasing clinical recognition of primary aldosteronism (PA) as a public health issue, its heightened risk profiles and the availability of targeted surgical/medical treatment being more understood, consensus in its diagnosis and management based on medical evidence, while recognizing the constraints of our real-world clinical practice in Taiwan, has not been reached. Methods: The Taiwan Society of Aldosteronism (TSA) Task Force acknowledges the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics into the management of PA. Results: When there is suspicion of PA, a plasma aldosterone to renin ratio (ARR) should be obtained initially. Patients with abnormal ARR will undergo confirmatory laboratory and image tests. Subtype classification with adrenal venous sampling (AVS) or NP-59 nuclear imaging, if AVS not available, to lateralize PA is recommended when patients are considered for adrenalectomy. The strengths and weaknesses of the currently available identification methods are discussed, focusing especially on result interpretation. Conclusion: With this consensus we hope to raise more awareness of PA among medical professionals and hypertensive patients in Taiwan, and to facilitate reconciliation of better detection, identification and treatment of patients with PA. Index words: Primary aldosteronism, Guideline, TAIPAI, TSA

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.

[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.

Background: Neuritic plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer’s disease (AD), while the role of brain amyloid deposition in the clinical manifestation or brain atrophy remains unresolved. We aimed to explore the relation between brain amyloid deposition, cortical thickness, and plasma biomarkers.Methods: We used 11C-Pittsburgh compound B-positron emission tomography to assay brain amyloid deposition, magnetic resonance imaging to estimate cortical thickness, and an immunomagnetic reduction assay to measure plasma biomarkers. We recruited 39 controls, 25 subjects with amnesic mild cognitive impairment (aMCI), and 16 subjects with AD. PiB positivity (PiB+) was defined by the upper limit of the 95% confidence interval of the mean cortical SUVR from six predefined regions (1.0511 in this study).Results: All plasma biomarkers showed significant between-group differences. The plasma Aβ40 level was positively correlated with the mean cortical thickness of both the PiB+ and PiB- subjects. The plasma Aβ40 level of the subjects who were PiB+ was negatively correlated with brain amyloid deposition. In addition, the plasma tau level was negatively correlated with cortical thickness in both the PiB+ and PiB- subjects. Moreover, cortical thickness was negatively correlated with brain amyloid deposition in the PiB+ subjects. In addition, the cut-off point of plasma tau for differentiating between controls and AD was higher in the PiB- group than in the PiB+ group (37.5 versus 25.6 pg/ml, respectively). Lastly, ApoE4 increased the PiB+ rate in the aMCI and control groups.Conclusion: The contributions of brain amyloid deposition to cortical atrophy are spatially distinct. Plasma Aβ40 might be a protective indicator of less brain amyloid deposition and cortical atrophy. It takes more tau pathology to reach the same level of cognitive decline in subjects without brain amyloid deposition, and ApoE4 plays an early role in amyloid pathogenesis.

The association between sarcoidosis and lymphoproliferative diseases is well-recognized. As fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) is increasingly utilized in lymphoma staging, it is important for clinicians to be aware of lymphoma mimickers on FDG-PET. Here we describe two patients with diffuse large B-cell lymphoma who presented with high muscular FDG-uptake. The first patient had histologically proven concomitant muscular sarcoidosis, while the second patient had primary skeletal muscle lymphoma. FDG-PET is of limited utility in discerning sarcoidosis and lymphoma, as both lesions are FDG-avid. Magnetic resonance imaging may provide clues to differentiate these two entities non-invasively. The “3 stripes” and “dark star” signs are characteristic for muscular sarcoidosis, whereas muscular lymphoma usually demonstrates homogenous gadolinium enhancement. Nevertheless, histological examination remains the gold standard in distinguishing hese two diseases. In conclusion, while FDG-PET may be useful in monitoring disease extent and activity of both sarcoidosis and lymphoma, and MRI may provide additional diagnostic information, biopsy is still recommended when clinical decision-making dictates confirmatory diagnosis.

The non-criteria neuropsychiatric manifestations of antiphospholipid syndrome include headache, dizziness, vertigo, seizure, depression and psychosis. There were still no objective methods qualified to detect the early central nervous system involvement in non-criteria antiphospholipid syndrome. We evaluated the effectiveness of Tc-99m ECD SPECT in assessing circulatory insufficiency in the brains of patients with antiphospholipid antibodies and neuropsychiatric symptoms but without thromboembolism.Patients with a history of positive antiphospholipid antibodies and neuropsychiatric symptoms composed the case group; patients without antiphospholipid antibody served as the control group. Subjects with a history of thromboembolism or autoantibodies to extractable nuclear antigens were excluded. All patients received Tc-99m ECD SPECT studies and were classified by the number of positive antiphospholipid antibodies they carried. The heterogeneity of brain perfusion was defined as the coefficient of variation of the SPECT signals. Analysis of variance (ANOVA) was applied to evaluate the differences between the groups.Total 60 adult patients were included in this study. There were 54 patients in the case group and 6 patients in the control group. The mean age was 38.3 ± 11.5 years. There were 52 women and 8 men. There was no significant difference in the mean brain perfusion between groups (P = 0.69). However, Tc-99m ECD SPECT demonstrated significant heterogeneity of brain perfusion in relation to the number of antiphospholipid antibodies (P = 0.01).This is the first study demonstrating that Tc-99m ECD SPECT can early detect the increased heterogeneity of brain circulation in non-criteria antiphospholipid antibody carriers.

PURPOSE:To determine whether acute kidney injury (AKI) is a risk factor for dementia. METHODS:This nationwide population-based cohort study was based on data from the Taiwan National Health Insurance Research Database for 2000-2011. The incidence and relative risk of dementia were assessed in 207788 patients hospitalized for AKI. The comparison control was selected using the propensity score based on age, sex, index year and comorbidities. RESULTS:During the 12-year follow-up, patients with AKI had a significantly higher incidence for developing dementia than did the controls (8.84 vs 5.75 per 1000 person-y). A 1.88-fold increased risk of dementia (95% confidence interval, 1.76-2.01) was observed after adjustment for age, sex, and several comorbidities (diabetes, hypertension, hyperlipidemia, head injury, depression, stroke, chronic obstructive pulmonary disease, coronary artery disease, congestive heart failure, atrial fibrillation, cancer, liver disease, chronic infection/inflammation, autoimmune disease, malnutrition). CONCLUSIONS:We found that patients with AKI exhibited a significantly increased risk of developing dementia. This study provides evidence on the association between AKI and long-term adverse outcomes. Additional clinical studies investigating the related pathways are warranted.

Background: Inappropriate skin incisions can make sentinel lymph node dissection difficult. A knowledge of the most common locations of the hotspot in the axilla helps in planning the incision. This information also helps to locate the lymph node preoperatively by ultrasound. The aim of this prospective study was to determine the most common location of the sentinel lymph node in the axilla. Methods: From January 2006 to December 2010, 974 consecutive patients who underwent sentinel lymph node dissection guided by 99mTc–sulfur colloid were included and the position of the hotspot in the axilla was recorded prospectively. The location of the hottest spot on the skin of the axilla was categorized into seven areas divided by five landmarks. Results: In 98.4% of our patients, the hotspot detected on the axilla skin before sentinel lymph node dissection was located in the area demarcated by the four landmarks of the hairline, a line tangential to and 2 cm below the center of the hairline, the lateral border of the pectoralis major muscle, and the mid-axillary line. Conclusion: The area between these four landmarks is the most frequent location of the sentinel lymph node identified using the radioisotope method. We suggest that this area should be carefully evaluated preoperatively by ultrasound for appropriate surgical planning. A skin incision in this area is also recommended when sentinel lymph node dissection is guided by blue dye.

Myoclonic astatic epilepsy (MAE) is characterized by multiple seizure types, which are often refractory. Although vagus nerve stimulation (VNS) is an alternative treatment for medically intractable seizures, its exact mechanism of action remains unclear. Herein, we report the case of a 4-year-old boy with intractable MAE who has been in a seizure-free status for 2 years and 3 months since 6 months after the implantation of a vagus nerve stimulator (Model 103, Cyberonics, Inc., Houston, TX). Various test results 6 months after VNS were compared with those before VNS. Results of an electroencephalograph revealed disappearance of epileptiform discharges and an increased beta–gamma spectrum rhythm. The brain diffusion-tensor imaging showed an increased ratio of fraction anisotropy in the right fimbria–fornix, indicating improved diffusion of the white matter tract, and 18F-fluorodeoxyglucose positron emission tomography revealed globally improved cerebral glucose metabolism. His cognitive and social–emotional performances also improved at 2 years after VNS. To the best of our knowledge, this is the first report to describe the effects of VNS on fimbria–fornix and glucose metabolism in MAE.

In the early 1990s, 9-(+)-11C-dihydrotetrabenazine (9-(+)-11C-DTBZ) was shown to be a useful positron emission tomography (PET) imaging agent for various neurodegenerative disorders. Here, we described the radiosynthesis and evaluation of the 9-(+)-11C-DTBZ analog, 10-(+)-11C-DTBZ, as a vesicular monoamine transporter 2 (VMAT2) imaging agent and compare it with 9-(+)-11C-DTBZ. 10-(+)-11C-DTBZ was obtained by 11C-MeI methylation with its 10 hydroxy precursor in the presence of 5 M NaOH. It had a slightly better average radiochemical yield of 35.3 ± 3.6% (decay-corrected to end of synthesis (EOS)) than did 9-(+)-11C-DTBZ (30.5 ± 2.3%). MicroPET studies showed that 10-(+)-11C-DTBZ had a striatum-to-cerebellum ratio of 3.74 ± 0.21 at 40 min post-injection, while the ratio of 9-(+)-11C-DTBZ was 2.50 ± 0.33. This indicated that 10-(+)-11C-DTBZ has a higher specific uptake in VMAT2-rich brain regions, and 10-(+)-11C-DTBZ may be a potential VMAT2 radioligand. Our experiment is the first study of 10-(+)-11C-DTBZ to include dynamic brain distribution in rat brains.

Technetium-99m methylene diphosphonate (Tc-99m MDP) whole-body bone scintigraphy (BS) has been widely used for detecting bone metastases. The aim of this study is to investigate the diagnostic accuracy of BS in detecting skeletal metastases for hepatocellular carcinoma (HCC) patients. In addition, the anatomic distribution of the metastatic bone lesions and the prognoses of the HCC patients are also analyzed. Methods: We retrospectively reviewed BS results of 179 consecutive HCC patients from January 2005 to December 2006 in our institution. The false negative (FN) rate, sensitivity, and specificity of BS were evaluated by patient-based and region-based analyses. Results: A total of 59 patients (33.0%) were confirmed of bone metastases. A total of 25 of these 59 patients (46.3%) had at least one lesion categorized as BS FN, and the bone metastatic status for 10 patients (17.0%) was underestimated by BS. The most observed metastatic site was spine while the most observed sites with FN of BS were the lower extremity. In total, there were 122 metastatic regions and 33 regions (27.0%) were FN of BS. Patients without any metastases survived significantly longer than any of other groups with metastases. Conclusion: High FN rate of Tc-99m MDP BS in detecting metastatic bone lesions for HCC patients was observed. In our opinion, careful history taking, meticulous examination, and a high index of suspicion are important for HCC patients with unexplained progressive pain in the musculoskeletal system. Even with negative results from Tc-99m MDP BS, the possibility of skeletal metastases cannot be indiscriminately excluded.

Niemann-Pick type C disease (NPC) is a rare autosomal recessive lipid storage disorder caused by impaired cellular functions in processing and transporting low-density lipoprotein-cholesterol. In this report, we present magnetic resonance imaging (MRI), magnetic resonance spectrography (MRS) and 18-fluoro-2-deoxyglucose positron emission tomography (PET) imaging results for a 22-year-old male NPC patient. The patient's two MRI studies (at age 19 years and 22 years) demonstrated progressive changes of brain atrophy that were more prominent at the frontal lobes, and hyperintense signals in bilateral parietal-occipital periventricular white matter. MRS (at age 19 years) revealed no significant decrease in N-acetyl aspartate/choline ratio in the left frontal central white matter. PET (at age 22 years) showed significant bilateral hypometabolism in the prefrontal cortex and dorsomedial thalamus, and hypermetabolism in the parietal-occipital white matter, lenticular nucleus of the basal ganglia, cerebellum and pons. The imaging findings noted by MRI, MRS and 18-fluoro-2-deoxyglucose PET offered a possible supplementary explanation for the clinical neurological symptoms of this NPC patient.

Thymic carcinoma is a rare anterior mediastinal malignancy. Most patients present initially with chest pain, cough or dyspnea. Asymptomatic patients account for less than one third of the total cases. Thymic carcinoma is aggressive and tends to metastasize to the lymph nodes, lungs, and bones, and less commonly to the liver, spleen, brain, and adrenal glands. We present a 49-year-old man who received abdominal ultrasound and magnetic resonance imaging for a health checkup, during which, a necrotic hepatic tumor was found incidentally. Fluorodeoxyglucose (FDG) positron emission tomography was performed to search for the primary site of malignancy, and lobulated FDG hypermetabolic lesions in the anterior mediastinum were found. The diagnosis of thymic carcinoma with liver metastasis was then confirmed after morphological and immunohistochemical studies of hepatic and mediastinal biopsy specimens.

Clinical decision-making in coronary artery disease requires integrated information on myocardial viability and coronary arteries, and cross-modality registration could facilitate this process. The recent emergence of hybrid positron emission tomography (PET)/computed tomography (CT) allows acquisition of this information in one study session; however, clinically useful software capable of presenting three-dimensional (3D) fused images to assess the relationship between myocardium and coronary arteries is limited. Methods: Patients with prior myocardial infarction were examined using electrocardiographically gated 18F-fluorodeoxyglucose PET and 16-slice CT. Results: There were seven patients; mean age was 59 ±15 years and six were male. Using 3D reconstruction, coregistration and interactive display, the topographical relationship between myocardial viability and coronary arteries was clearly identified. Conclusion: We present a protocol to acquire CT coronary angiography and PET data and to visualize 3D fused images with an interactive visualization interface. This image coregistration is potentially useful to facilitate the process of image interpretation and decision-making.

Sentinel lymph node (LN) biopsy has been widely adopted in the axillary staging of clinical node-negative breast cancer patients. This study aimed to evaluate the accuracy of radio-guided sentinel LN (SLN) biopsy (SLNB) using the periareolar injection technique for predicting the histopatho-logic status of axillary LNs in early breast cancer patients. Methods: Between November 2003 and November 2004 in the National Taiwan University Hospital, radio-guided SLNB using the periareolar injection technique was consecutively performed in 213 female patients with early breast cancer (stage T1 and T2) but without clinically palpable axillary LN and previous chemotherapy. Two mCi of filtered (0.22 mm) 99mTc-sulfur colloid were injected in the afternoon 1 day before surgery (2-day protocol) or 1 mCi of the same radiopharmaceutical was injected on the morning of the surgery (1-day protocol). During surgery, a handheld gamma probe was used to identify the LNs with radioactivity in the axilla. A node was deemed a SLN if its radioactivity was > 10% of the hottest node. All the SLNs identified were removed for histology. Results: Radioactive SLN was identified at surgery in 207 patients. The SLN identification rate was 97.2% (207/213). Of these 207 patients, 163 patients had received both SLNB and axillary LN dissection. Among these 163 patients, 77 patients had LN metastases and four had negative SLN but positive non-SLN. The false-negative rate of SLNB for the detection of axillary LN metastases was 5.2% (4/77). There were no statistical differences between false-negative and SLN positive groups for all factors. Conclusion: Our study suggests that SLNB with periareolar injection of radiocolloid provides valuable information on the axillary nodal status in patients with early breast cancer. [J Formos Med Assoc 2007; 106(1):44-50]

Myocardial perfusion imaging (MPI) using gated single-photon emission tomography (gSPECT) may underestimate the severity of coronary artery disease (CAD). This study aimed to evaluate the significance of combined parameters derived from gSPECT, as well as treadmill stress test parameters, in the detection of severe CAD.A total of 211 consecutive patients referred for exercise MPI between June 2011 and June 2013 (who received invasive coronary angiography within six months after MPI) were retrospectively reviewed. Exercise MPI was performed with Bruce protocol and 201Tl injected at peak exercise. Gated SPECT was performed using a cadmium-zinc-telluride camera and processed by QPS/QGS software. Perfusion defect abnormalities such as sum stress score (SSS); sum difference score, algorithm-derived total perfusion deficits, transient ischemic dilatation ratios of end-diastolic volumes and end-systolic volumes, post-stress changes in ejection fraction, and lung/heart ratio (LHR) were calculated. Treadmill parameters, including ST depression (STD) at the 1st and 3rd minutes of recovery stage (1'STD and 3'STD), maximal STD corrected by heart rate increment (ST/HR), heart rate decline in 1st and 3rd minutes of recovery stage, recovery heart rate ratio (HR ratio), systolic and mean blood pressure ratios (SBP ratio and MAP ratio) during recovery phase were recorded. Diagnostic performances of these parameters were analyzed with receiver operating characteristic (ROC) analysis and logistic regression for detection of left main (≥ 50%) or 3-vessel disease (all ≥ 70% luminal stenosis) on invasive angiography.Among various MPI and treadmill parameters used for detection of severe CAD, SSS and ST/HR had the highest AUC (0.78, 0.73, p = NS) and best cut-off values (SSS > 6, ST/HR > 17.39 10-2mV/bpm), respectively. By univariate logistic regression, all parameters except 1'HRR, 3'HRR, SBP and MAP ratios increased the odds ratio of severe CAD. Only increased L/H ratio, 3'STD, and HR ratio remained significant after multivariate regression. The predicted values of combined MPI and treadmill parameters (LHR, 3'STD, and HR ratio) gave the best ROC (AUC: 0.91) than any individual parameter or parameter combination.Of all treadmill and gSPECT parameters, the combination of MPI and treadmill parameters can offer better diagnostic performance for severe CAD.