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1.
Dig Endosc ; 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32462727

RESUMO

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 diagnosed. In conclusion, 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.

2.
Neuromodulation ; 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32270579

RESUMO

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.

3.
Appl Radiat Isot ; 158: 108871, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32113705

RESUMO

Automated three-step two-pot production of no-carrier-added (NCA) [18F]FDOPA was first implemented in the iPHASE FlexLab module. Decay-corrected radiochemical yield (RCY) of [18F]FDOPA synthesized by this method was 10~14% (n = 7) with a synthesis time of ~110 min [18F]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.

4.
Medicine (Baltimore) ; 99(10): e18988, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150047

RESUMO

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.


Assuntos
Antígeno CA-19-9/sangue , Cisto Dermoide/diagnóstico , Cistos Ovarianos/diagnóstico , Adulto , Biomarcadores Tumorais/sangue , Cisto Dermoide/sangue , Cisto Dermoide/diagnóstico por imagem , Cisto Dermoide/cirurgia , Diagnóstico Diferencial , Feminino , Fluordesoxiglucose F18 , Humanos , Cistos Ovarianos/sangue , Cistos Ovarianos/diagnóstico por imagem , Cistos Ovarianos/cirurgia , Ovariectomia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos
5.
Brain Behav ; 10(3): e01548, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31989779

RESUMO

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 on 11 C-labeled Pittsburgh compound B positron emission tomography (PET). Plasma biomarker measures indicated an AD profile with increased Aß1-42 (18.66 pg/ml; cutoff: 16.42 pg/ml), Aß1-42/Aß1-40 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.

6.
Stroke ; 51(1): 202-208, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31726962

RESUMO

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.


Assuntos
Angiopatia Amiloide Cerebral/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Angiografia por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
J Nucl Cardiol ; 27(1): 269-279, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30109593

RESUMO

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 201Tl 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.

8.
PLoS One ; 14(7): e0217384, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31260447

RESUMO

[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.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Carbolinas/síntese química , Meios de Contraste/síntese química , Compostos Radiofarmacêuticos/síntese química , Proteínas tau/química , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Animais , Disponibilidade Biológica , Carbolinas/sangue , Carbolinas/farmacocinética , Meios de Contraste/farmacocinética , Avaliação Pré-Clínica de Medicamentos , Expressão Gênica , Haplorrinos , Humanos , Injeções Intravenosas , Macaca , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Radiometria , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual , Proteínas tau/genética
9.
Ther Adv Neurol Disord ; 12: 1756286419844113, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31105769

RESUMO

Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease caused by ß -amyloid (Aß) 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.

10.
Strahlenther Onkol ; 195(8): 707-718, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30610356

RESUMO

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 (SUVmax), 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 Ktrans <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.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Aumento da Imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Imagem por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Meios de Contraste , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação
11.
Neurology ; 92(8): e774-e781, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30674594

RESUMO

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 11C-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.


Assuntos
Encéfalo/diagnóstico por imagem , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina , Angiopatia Amiloide Cerebral/complicações , Hemorragia Cerebral/etiologia , Doenças de Pequenos Vasos Cerebrais/complicações , Estudos Transversais , Feminino , Humanos , Hemorragia Intracraniana Hipertensiva/diagnóstico por imagem , Hemorragia Intracraniana Hipertensiva/etiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Taiwan , Tiazóis
12.
J Nucl Cardiol ; 26(5): 1584-1595, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-29484543

RESUMO

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.

13.
Ci Ji Yi Xue Za Zhi ; 30(3): 169-175, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30069126

RESUMO

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 ß-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.

14.
Front Aging Neurosci ; 10: 175, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29967578

RESUMO

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 Aß40 level was positively correlated with the mean cortical thickness of both the PiB+ and PiB- subjects. The plasma Aß40 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 Aß40 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.

15.
Stroke ; 49(6): 1515-1517, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29695464

RESUMO

BACKGROUND AND PURPOSE: We evaluated whether lacunes in centrum semiovale (lobar lacunes) were associated with cerebral amyloid angiopathy (CAA) markers in an Asian intracerebral hemorrhage (ICH) population. METHODS: One hundred ten patients with primary ICH were classified as CAA-ICH (n=24; mean age, 70.9±13.9) or hypertensive ICH (n=86; mean age, 59.3±13.0) according to the presence of strictly lobar (per modified Boston criteria) or strictly deep bleeds (both ICH and cerebral microbleeds), respectively. Lacunes were evaluated in the supratentorial area and classified as lobar or classical deep based on the location. A subgroup of 36 patients also underwent Pittsburgh Compound B positron emission tomography to measure cerebral amyloid deposition and global standardized uptake value ratio were calculated. RESULTS: Lobar lacunes were more frequent in CAA-ICH than hypertensive ICH (29.2 versus 11.6%; P=0.036). In multivariable models, lobar lacunes were associated with lobar cerebral microbleed (odds ratio, 6.8; 95% confidence interval, 1.6-29.9; P=0.011) after adjustment for age, sex, hypertension, and white matter hyperintensity. In 15 CAA-ICH and 21 hypertensive ICH patients with Pittsburgh Compound B positron emission tomography, correlation analyses between lobar lacune counts and global standardized uptake value ratio showed positive association (ρ=0.40; P=0.02) and remained significant after adjustment for age (r=0.34; P=0.04). CONCLUSIONS: Our findings expand on recent work showing that lobar lacunes are more frequent in CAA-ICH than hypertensive ICH. Their independent association with lobar cerebral microbleeds and brain amyloid deposition suggests a relationship with CAA even in an Asian cohort with overall higher hypertensive load.


Assuntos
Angiopatia Amiloide Cerebral/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Imagem por Ressonância Magnética , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Angiopatia Amiloide Cerebral/complicações , Hemorragia Cerebral/complicações , Diagnóstico Diferencial , Feminino , Humanos , Hemorragia Intracraniana Hipertensiva/diagnóstico por imagem , Hemorragia Intracraniana Hipertensiva/fisiopatologia , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral Lacunar/complicações
16.
Eur J Nucl Med Mol Imaging ; 45(7): 1205-1217, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29476229

RESUMO

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 (18F-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, IAUC 60 , K trans , k ep , v e ), 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.


Assuntos
Imagem por Ressonância Magnética , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Idoso , Biomarcadores , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Prognóstico , Estudos Prospectivos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Carga Tumoral
17.
Sci Rep ; 8(1): 3651, 2018 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-29483544

RESUMO

Autoimmune pancreatitis (AIP) shares overlapping clinical features with pancreatic cancer (PC). Importantly, treatment of the two conditions is different. We investigated the clinical usefulness of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with suspected AIP before treatment. From September 2008 to July 2016, 53 patients with suspected AIP at National Taiwan University Hospital had PET/CT prior to therapy to exclude malignancy and evaluate the extent of inflammation. Their scans were compared with those from 61 PC patients. PET imaging features were analyzed using logistic regression. Significant differences in pancreatic tumor uptake morphology, maximum standardized uptake value, high-order primary tumor texture feature (i.e. high-gray level zone emphasis value), and numbers and location of extrapancreatic foci were found between AIP and PC. Using the prediction model, the area under curve of receiver-operator curve was 0.95 (P < 0.0001) with sensitivity, specificity, positive predictive, and negative predictive values of 90.6%, 84.0%, 87.9%, and 87.5% respectively, in differentiating AIP from PC. FDG PET/CT offers high sensitivity, albeit slightly lower specificity in differentiating AIP from PC. Nonetheless, additional systemic inflammatory foci detected by the whole body PET/CT help confirm diagnosis of AIP in these patients before initiating steroid therapy, especially when biopsy is inconclusive.


Assuntos
Doenças Autoimunes/diagnóstico por imagem , Pancreatite/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Estudos de Casos e Controles , Diagnóstico Diferencial , Fluordesoxiglucose F18 , Humanos , Modelos Logísticos , Neoplasias Pancreáticas/diagnóstico por imagem
18.
Eur J Nucl Med Mol Imaging ; 45(4): 567-574, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29164302

RESUMO

PURPOSE: In patients with stable coronary artery disease (CAD), two main options exist to guide management: initial invasive coronary angiography (CAG), or selective CAG after risk stratification using myocardial perfusion imaging (MPI). This study compared clinical outcomes between these two strategies in a large, real-world population. METHODS: The initial cohort comprised 1,000,000 randomly selected patients who had been entered in the National Health Insurance Research Database of Taiwan between 2000 and 2011. Patients with acute coronary syndromes, prior myocardial infarction (MI) or coronary revascularization, and prior treadmill testing or stress echocardiography were excluded. The remaining patients with suspected or known CAD were divided into those in whom initial CAG had been performed and those in whom initial MPI had been performed, and were followed until the end of 2011 for all-cause mortality, MI, and revascularization. A Cox proportional hazards model was used to estimate the risk of events after adjusting for covariates. RESULTS: The MPI and CAG groups each comprised 4,495 patients after frequency matching, with a similar Charlson comorbidity index (CCI). The MPI group had a significantly and dramatically lower incidence of revascularization (729 vs. 2,380, p < 0.001), MI (268 vs. 1,044, p < 0.001), and all-cause mortality (522 vs. 784, p < 0.001) than the CAG group. Multivariable analysis adjusting for age, gender, CCI, and comorbidities showed that in the MPI group fewer patients had revascularization (HR 0.24, 95% CI 0.22-0.26) and MI (HR 0.23, 95% CI 0.20-0.26), and the rate of all-cause mortality was lower (HR 0.58, 95% CI 0.52-0.64). CONCLUSIONS: In patients with suspected stable CAD, compared with initial invasive CAG, a selective strategy guided by MPI was associated with lower rates of revascularization and MI and improved survival.


Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Imagem de Perfusão do Miocárdio , Estudos de Coortes , Humanos , Taiwan
19.
J Magn Reson Imaging ; 47(1): 191-199, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28480541

RESUMO

PURPOSE: To evaluate the response in patients undergoing SBRT using dynamic contrast-enhanced (DCE) integrated magnetic resonance positron emission tomography (MR-PET). Stereotactic body radiation therapy (SBRT) is efficacious as a front-line local treatment for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We prospectively enrolled 19 lung tumors in 17 nonmetastatic NSCLC patients who were receiving SBRT as a primary treatment. They underwent DCE-integrated 3T MR-PET before and 6 weeks after SBRT. The following image parameters were analyzed: tumor size, standardized uptake value (SUV), apparent diffusion coefficient, Ktrans , kep , ve , vp , and iAUC60 . Chest computed tomography (CT) was performed at 3 months after SBRT. RESULTS: SBRT treatment led to tumor changes including significant decreases in the SUVmax (-61%, P < 0.001), Ktrans mean (-72%, P = 0.005), Ktrans standard deviation (SD; -85%, P = 0.046), kep mean (-53%, P = 0.014), kep SD (-63%, P = 0.001), and vp SD (-58%, P = 0.002). The PET SUVmax was correlated with the MR kep mean (P = 0.002) and kep SD (P < 0.001). The percentage reduction in Ktrans mean (P < 0.001) and kep mean (P = 0.034) at 6 weeks post-SBRT were significantly correlated with the percentage reduction in tumor size, as measured using CT at 3 months after SBRT. Univariate analyses revealed a trend toward disease progression when the initial SUVmax > 10 (P = 0.083). CONCLUSION: In patients with NSCLC who are receiving SBRT, DCE-integrated MR-PET can be used to evaluate the response after SBRT and to predict the local treatment outcome. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:191-199.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Imagem por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Radiocirurgia , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Meios de Contraste/química , Progressão da Doença , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18/química , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Estudos Prospectivos , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
Hepatology ; 67(2): 586-599, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28646552

RESUMO

Several strategies to improve the efficacy of radiation therapy against hepatocellular carcinoma (HCC) have been investigated. One approach is to develop radiosensitizing compounds. Because histone deacetylase 4 (HDAC4) is highly expressed in liver cancer and known to regulate oncogenesis through chromatin structure remodeling and controlling protein access to DNA, we postulated that HDAC4 inhibition might enhance radiation's effect on HCC cells. HCC cell lines (Huh7 and PLC5) and an ectopic xenograft were pretreated with HDAC inhibitor or short hairpin RNA to knock down expression of HDAC4 and then irradiated (2.5-10.0 Gy). We evaluated cell survival by a clonogenic assay; apoptosis by Annexin V immunofluorescence; γH2AX, Rad51, and HDAC4 by immunofluorescence staining; HDAC4, Rad51, and ubiquitin-conjugating enzyme 9 (Ubc9) in HCC cell nuclei by cell fractionation and confocal microscopy; physical interaction between HDAC4/Rad51/Ubc9 by immunoprecipitation; and the downstream targets of HDAC4 knockdown by immunoblotting. Both HDAC4 knockdown and HDAC inhibitor enhanced radiation-induced cell death and reduced homologous recombination repair of DNA double-strand breaks and protein kinase B activation, leading to increased apoptosis. HDAC4 knockdown with or without an HDAC inhibitor significantly delayed tumor growth in a radiation-treated xenograft model. Radiation stimulated nuclear translocation of Rad51 in an HDAC4-dependent manner and the binding of Ubc9 directly to HDAC4, which led to Ubc9 acetylation. Moreover, these effects were accompanied by HDAC4/Ubc9/Rad51 complex dissociation through inhibiting nuclear translocation. Conclusion: HDAC4 signaling blockade enhances radiation-induced lethality in HCC cells and xenografts. These findings raise the possibility that HDAC4/Ubc9/Rad51 complex in DNA repair may be a target for radiosensitization of HCC. (Hepatology 2018;67:586-599).


Assuntos
Carcinoma Hepatocelular/radioterapia , Reparo do DNA/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Neoplasias Hepáticas/radioterapia , Radiossensibilizantes/farmacologia , Proteínas Repressoras/antagonistas & inibidores , Enzimas de Conjugação de Ubiquitina/antagonistas & inibidores , Transporte Ativo do Núcleo Celular , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/metabolismo , Humanos , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Rad51 Recombinase/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
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