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1.
Nat Med ; 26(3): 398-407, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32161412

RESUMO

Development of tau-based therapies for Alzheimer's disease requires an understanding of the timing of disease-related changes in tau. We quantified the phosphorylation state at multiple sites of the tau protein in cerebrospinal fluid markers across four decades of disease progression in dominantly inherited Alzheimer's disease. We identified a pattern of tau staging where site-specific phosphorylation changes occur at different periods of disease progression and follow distinct trajectories over time. These tau phosphorylation state changes are uniquely associated with structural, metabolic, neurodegenerative and clinical markers of disease, and some (p-tau217 and p-tau181) begin with the initial increases in aggregate amyloid-ß as early as two decades before the development of aggregated tau pathology. Others (p-tau205 and t-tau) increase with atrophy and hypometabolism closer to symptom onset. These findings provide insights into the pathways linking tau, amyloid-ß and neurodegeneration, and may facilitate clinical trials of tau-based treatments.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Padrões de Herança/genética , Proteínas tau/metabolismo , Adulto , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico por imagem , Atrofia , Encéfalo/patologia , Cognição , Progressão da Doença , Feminino , Fluordesoxiglucose F18/química , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Fosforilação , Placa Amiloide/patologia , Solubilidade , Proteínas tau/líquido cefalorraquidiano
2.
PLoS One ; 15(3): e0230292, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32191714

RESUMO

This single-institution cross-sectional study aimed to grasp the prevalence and features of neurocognitive dysfunction in HIV-infected hemophilia patients in Japan. We conducted neuropsychological tests and medical examinations in 56 HIV-infected hemophilia patients who received outpatient treatment at the AIDS Clinical Center, National Center for Global Health and Medicine. A total of 388 HIV-infected non-hemophilia patients who received outpatient treatment at the same institution were included as a control group. To investigate sites responsible for neurocognitive dysfunction in HIV-infected hemophilia patients using brain FDG-PET/CT scans, the accumulation of FDG in each brain region was compared. Approximately 50% of HIV-infected hemophilia patients had neurocognitive dysfunction. The prevalence of asymptomatic neurocognitive impairment was high (34%). Neurocognitive dysfunction was associated with educational level in HIV-infected hemophilia patients. In the symptomatic group, hemophilic arthropathy and history of cerebrovascular disorders were associated with neurocognitive dysfunction. Left temporal lobe function was reduced in the symptomatic group.


Assuntos
Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Fluordesoxiglucose F18/química , Infecções por HIV/complicações , Infecções por HIV/diagnóstico por imagem , Hemofilia A/complicações , Hemofilia A/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
3.
Chem Commun (Camb) ; 55(96): 14442-14445, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31724668

RESUMO

We firstly perpared liposome coated [Ir(pq)2(bpy)]Cl (Ir@liposome) as a transducer for radiopharmaceutical (18F-FDG) excited phosphorescence imaging (REPI). Ir@liposome-based REPI exhibited deep tissue penetration and high signal-to-noise ratio in the tumor.


Assuntos
Complexos de Coordenação/química , Irídio/química , Nanopartículas/química , Imagem Óptica/métodos , Compostos Radiofarmacêuticos/química , Animais , Linhagem Celular Tumoral , Fluordesoxiglucose F18/química , Humanos , Lipossomos/química , Camundongos , Razão Sinal-Ruído
4.
PLoS One ; 14(10): e0223141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31589623

RESUMO

One of the main technical challenges of PET/MRI is to achieve an accurate PET attenuation correction (AC) estimation. In current systems, AC is accomplished by generating an MRI-based surrogate computed tomography (CT) from which AC-maps are derived. Nevertheless, all techniques currently implemented in clinical routine suffer from bias. We present here a convolutional neural network (CNN) that generated AC-maps from Zero Echo Time (ZTE) MR images. Seventy patients referred to our institution for 18FDG-PET/MR exam (SIGNA PET/MR, GE Healthcare) as part of the investigation of suspected dementia, were included. 23 patients were added to the training set of the manufacturer and 47 were used for validation. Brain computed tomography (CT) scan, two-point LAVA-flex MRI (for atlas-based AC) and ZTE-MRI were available in all patients. Three AC methods were evaluated and compared to CT-based AC (CTAC): one based on a single head-atlas, one based on ZTE-segmentation and one CNN with a 3D U-net architecture to generate AC maps from ZTE MR images. Impact on brain metabolism was evaluated combining voxel and regions-of-interest based analyses with CTAC set as reference. The U-net AC method yielded the lowest bias, the lowest inter-individual and inter-regional variability compared to PET images reconstructed with ZTE and Atlas methods. The impact on brain metabolism was negligible with average errors of -0.2% in most cortical regions. These results suggest that the U-net AC is more reliable for correcting photon attenuation in brain FDG-PET/MR than atlas-AC and ZTE-AC methods.


Assuntos
Algoritmos , Encéfalo/diagnóstico por imagem , Fluordesoxiglucose F18/química , Imagem por Ressonância Magnética , Imagem Multimodal , Redes Neurais de Computação , Tomografia por Emissão de Pósitrons , Idoso , Análise de Variância , Feminino , Humanos , Masculino
5.
BMC Infect Dis ; 19(1): 845, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615426

RESUMO

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) shows great potential for diagnosis and assessing therapeutic response of tuberculous spondylitis. Tuberculous spondylitis required long-term anti-tuberculosis (TB) medication therapy, and the optimal duration of therapy is controversial. There is still no clear way to tell when the anti-TB therapy can safely be discontinued. CASE PRESENTATION: Three patients with tuberculous spondylitis were evaluated for therapeutic response using 18F-FDG PET/magnetic resonance imaging (MRI). Clinical and hematological improvements were achieved after about 12 months of anti-TB medication therapy, and we considered whether to discontinue the therapy. There was no relapse during one year of follow-up after discontinuation of 12 months anti-TB medication based on the low maximum standardized uptake value (SUVmax) of 1.83 in one patient. However, the other two patients continued further anti-TB medication therapy based on the high SUVmax of 4.14 and 7.02, which were suspected to indicate active residual lesions in the abscess or granulation tissues. Continuous TB was confirmed by the bacterial and histological examinations. CONCLUSIONS: 18F-FDG PET/MRI has metabolic and anatomical advantages for assessing therapeutic response in TB spondylitis, and can be considered as a helpful independent and alternative method for determining the appropriate time to discontinue anti-TB medication.


Assuntos
Compostos Radiofarmacêuticos/química , Espondilite/diagnóstico , Tuberculose da Coluna Vertebral/diagnóstico , Adulto , Antituberculosos/uso terapêutico , Feminino , Fluordesoxiglucose F18/química , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Tomografia por Emissão de Pósitrons , Espondilite/diagnóstico por imagem , Espondilite/tratamento farmacológico , Tuberculose da Coluna Vertebral/diagnóstico por imagem , Tuberculose da Coluna Vertebral/tratamento farmacológico
7.
Jpn J Clin Oncol ; 49(10): 895-900, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504700

RESUMO

The Lugano classification was published in 2014 to form the basis for revising the recommendations regarding anatomic staging and evaluation of disease before and after therapy. This staging system was adopted by the eighth edition of the Cancer Staging Manual of the American Joint Committee on Cancer. In this review, we aimed to discuss this updated staging system for malignant lymphomas. The most important change was that fluorodeoxyglucose positron emission tomography/computed tomography became the new standard imaging technique for staging of all fluorodeoxyglucose-avid histologies. Due to the introduction of fluorodeoxyglucose positron emission tomography/computed tomography for staging, the evaluation of not only lymph node involvement but also organ involvement, including liver or spleen, has become simplified. Furthermore, it is possible to eliminate bone marrow biopsies in patients with Hodgkin lymphoma and diffuse large B-cell lymphoma. Although patients were grouped according to the absence (A) or presence (B) of disease-related symptoms based on the previous classification, only the patients with Hodgkin lymphoma need to be assigned the designations A or B in this revision. Hopefully, these revised recommendations will improve patient management and the conduct of clinical trials.


Assuntos
Linfoma/classificação , Linfoma/patologia , Fluordesoxiglucose F18/química , Humanos , Linfonodos/patologia , Linfoma/diagnóstico por imagem , Estadiamento de Neoplasias , Especificidade de Órgãos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
8.
J Nucl Med ; 60(10): 1350-1358, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31481573

RESUMO

Prostate cancer is a very heterogeneous disease, and contemporary management is focused on identification and treatment of the prognostically adverse high-risk tumors while minimizing overtreatment of indolent, low-risk tumors. In recent years, imaging has gained increasing importance in the detection, staging, posttreatment assessment, and detection of recurrence of prostate cancer. Several imaging modalities including conventional and functional methods are used in different clinical scenarios with their very own advantages and limitations. This continuing medical education article provides an overview of available imaging modalities currently in use for prostate cancer followed by a more specific section on the value of these different imaging modalities in distinct clinical scenarios, ranging from initial diagnosis to advanced, metastatic castration-resistant prostate cancer. In addition to established imaging indications, we will highlight some potential future applications of contemporary imaging modalities in prostate cancer.


Assuntos
Imagem Multimodal/métodos , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Antígenos de Superfície/metabolismo , Ácidos Carboxílicos/química , Colina/química , Ciclobutanos/química , Progressão da Doença , Fluordesoxiglucose F18/química , Glutamato Carboxipeptidase II/metabolismo , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética Multiparamétrica , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia por Emissão de Pósitrons , Cintilografia , Nanomedicina Teranóstica , Tomografia Computadorizada por Raios X , Imagem Corporal Total
9.
Neurochem Res ; 44(9): 2092-2102, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31377996

RESUMO

The aim of this study was to evaluate the diagnostic efficacy of 18F-FDG PET/MRI in two different peripheral neuropathic pain models using the injured rat sciatic nerves. Twelve rats, with operation on left sciatic nerves, were evenly divided into three groups: sham surgery (control group), crushing injury and chronic constriction injury (CCI) (experimental groups). The nerve damage was assessed at 3 weeks postoperatively using following methods: paw withdrawal threshold values (RevWT), maximum standardized uptake values on PET/MRI images (SUVR), and counting the number of myelinated axons in proximal and distal sites of nerve injury (MAxR). The results were quantified and statistically analyzed. Compared to the control group, the crushing injury demonstrated significant differences in RevWT (p < 0.0001) and SUVR (p = 0.027) and the CCI group demonstrated significant differences in RevWT (p < 0.0001), SUVR (p = 0.001) and MAxR (p = 0.048). There were no significant differences between the two experimental groups for all assessments. Correlation analysis demonstrated that RevWT and SUVR assessments were highly correlated (r = -- 0.710, p = 0.010), and SUVR and MAxR were highly correlated (r = 0.611, p = 0.035). However, there was no significant correlation between RevWT and MAxR. The PET scan may be a valuable imaging modality to enable noninvasive, objective diagnosis of neuropathic pain caused by peripheral nerve injury. Also, MRI fused with PET may help clarify the anatomic location of soft tissue structures, including the peripheral nerves.


Assuntos
Fluordesoxiglucose F18/química , Neuralgia/diagnóstico por imagem , Traumatismos dos Nervos Periféricos/diagnóstico por imagem , Compostos Radiofarmacêuticos/química , Neuropatia Ciática/diagnóstico por imagem , Animais , Radioisótopos de Flúor/química , Imagem por Ressonância Magnética , Masculino , Traumatismos dos Nervos Periféricos/patologia , Tomografia por Emissão de Pósitrons , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Neuropatia Ciática/patologia
10.
PLoS One ; 14(8): e0221516, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31454368

RESUMO

BACKGROUND: The aim of our study is to describe the FDG-PET/CT findings in patients with tuberculosis and to correlate them with the patient's prognosis. METHODS: We retrospectively collected data from patients with tuberculosis, who had an FDG-PET/CT performed prior to treatment initiation from 2010 to 2015. RESULTS: Forty-seven out of 504 patients with active tuberculosis diagnosis (9.33%) underwent an FDG-PET/CT. The reasons for performing the FDG-PET/CT were: characterization of a pulmonary nodule (24; 51.1%), study of fever of unknown origin (12; 25.5%), study of lymph node enlargement (5; 10.6%) and others (6; 12.8%). Median age was 64 (IQR 50-74) years and 31 (66%) patients were male. Twenty-six (55.3%) patients had an immunosuppressant condition. According to the FDG-PET/CT, 48.6% of the patients had more than 1 organ affected and 46.8% had lymph node involvement. Median SUVmax of the main lesion was 5 (IQR 0.28-11.85). We found an association between the FDG accumulation and the size of the main lesion with a correlation coefficient of 0.54 (p<0.002). Patients with an unsuccessful outcome had a higher ratio SUVmax main lesion / SUVmean liver (1.92 vs 7.67, p<0.02). CONCLUSIONS: In our cohort, almost half of the patients had more than 1 organ affected and 46.8% of them had lymph node involvement. FDG uptake was associated with the size of the main lesion and seems to be related to the treatment outcome. The extent of its potential to be used as an early predictor of treatment success still needs to be defined.


Assuntos
Fluordesoxiglucose F18/química , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tuberculose/diagnóstico por imagem , Idoso , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Tuberculose/epidemiologia , Adulto Jovem
11.
Biomed Pharmacother ; 117: 109168, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31334700

RESUMO

Sites of infection and inflammation can be misleading in oncology PET/CT imaging because these areas commonly show 18F-FDG activity. Caution in the interpretation must be taken to avoid the misdiagnosis of malignancy. Utilization of both CT findings as well as patient history can help differentiate benign infectious and inflammatory processes from malignancy, although occasionally additional work-up may be required. This article discusses the mechanism of 18F-FDG uptake in infection and inflammation with illustrative examples.


Assuntos
Fluordesoxiglucose F18/química , Infecções/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Animais , Fluordesoxiglucose F18/metabolismo , Humanos
12.
Interdiscip Sci ; 11(2): 300-306, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31264053

RESUMO

Primary central nervous system lymphomas (PCNSLs) are rare progressive brain tumors, whose managements are significantly different from other solid tumors, especially glioblastomas. Therefore, an early diagnosis is of great significance. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET), which can measure the glucose metabolic rate in the brain, is an increasingly common tool for early diagnosis. Twenty-five immunocompetent patients with PCNSL were reviewed in this study to describe the general characteristics of PCNSL patients' 18F-FDG-PET scans. Quantitative features included a radically enhanced maximum standardized uptake value (SUVmax) with a mean value of 23.8 ± 7.9 and a 5.8 ± 1.8 mean ratio of tumor-to-normal contralateral cortex activity (T/N). Visual characteristics, such as favored locations in the brain, lesion numbers, tumor shape, metabolic inhibition, and structural shift were determined as well. PCNSL was found to favor the cortex, especially the frontal lobe, followed by the basal ganglia and corpus callosum. All PCNSLs were near the lateral ventricular area. Tumor shapes were subdivided into three groups: diffuse, round, and irregular patterns. Reduced radiation was observed in the ipsilateral cortex, the basal ganglia and the contralateral cerebellum. The lateral ventricles were prone to be compressed on the side ipsilateral to the tumor, pushing the midline towards the contralateral side of the brain. In conclusion, aside from SUVmax and T/N values, other visual characteristics are also available to facilitate the differentiation of PCNSLs from other brain conditions on 18F-FDG-PET scans.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Fluordesoxiglucose F18/química , Linfoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade
13.
PLoS One ; 14(6): e0218416, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31237886

RESUMO

BACKGROUND: In some patients with metastatic differentiated thyroid cancer, even if they had substantial of radioactive iodine (RAI) uptake, the RAI therapy response was poor. We investigated the usefulness of FDG PET/CT for the early prediction of RAI therapy response in the patients with metastatic differentiated thyroid cancer (DTC). METHODS: The 54 metastatic DTC patients who underwent both RAI therapy scan and FDG PET/CT at the same period were enrolled in the study. Clinical information and several parameters from RAI therapy scan and FDG PET/CT were investigated. Therapeutic response of RAI was assessed as two categories: response rate (RR) and disease control rate (DCR). RESULTS: Twenty-two patients (41%) had therapeutic response to RAI therapy, whereas 32 (59%) patients did not. There were no significant differences in age, sex, stage, histology, metastasis site, stimulated Tg or Tg-Ab, therapeutic doses, and even RAI uptake pattern among two groups. However, there was a significant negative correlation between FDG avidity of metastatic lesions and RR (OR = 0.233; p = 0.016). Although the patient group with only RAI uptake showed a significant correlation with RR (OR = 5.833; p = 0.01), the patient group with both RAI and FDG uptake did not show any significant correlation with RR. In the subgroup analysis, uptake grades of RAI or FDG was well correlated with DCR. CONCLUSIONS: The patient group with FDG uptake in metastatic DTC showed poor response to RAI therapy regardless of the degree of RAI uptake. Therefore, FDG PET/CT may help us identify the patients with radioiodine refractory DTC and establish an appropriate treatment strategy in the early period.


Assuntos
Diferenciação Celular , Fluordesoxiglucose F18/química , Radioisótopos do Iodo/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias da Glândula Tireoide/terapia , Adulto Jovem
14.
Ups J Med Sci ; 124(2): 119-124, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31179853

RESUMO

Aims: The demand for specimen collection for genomic profiling is rapidly increasing in the era of personalized medicine. Percutaneous needle biopsy is recognized as minimally invasive, but the feasibility of comprehensive genomic analysis using next-generation sequencing (NGS) is not yet clear. The purpose of this study was to evaluate the feasibility of genomic analysis using NGS with specimens obtained by image-guided percutaneous needle biopsy with 18-G needles. Patients and methods: Forty-eight patients who participated in a clinical study of genomic profiling with NGS with the specimen obtained by image-guided needle biopsy were included. All biopsies were performed under local anesthesia, with imaging guidance, using an 18-G cutting needle. A retrospective chart review was performed to determine the rate of successful genomic analysis, technical success rate of biopsy procedure, adverse events, rate of success in pathological diagnosis, and cause of failed genomic analysis. Results: The success rate of genomic analysis was 79.2% (38/48). The causes of failure were unprocessed for DNA extraction due to insufficient specimen volume (6/10), insufficient DNA volume (2/10), and deteriorated DNA quality (2/10). The rate of successful genomic analysis excluding NGS analysis that failed for reasons unrelated to the biopsy procedures was 95.2% (40/42). Technical success of biopsy was achieved in all patients without severe adverse events. The rate of success in the pathological diagnosis was 97.9% (47/48). Conclusions: Image-guided needle biopsy specimens using an 18-G cutting needle yielded a successful NGS genomic analysis rate with no severe adverse events and could be an adoptable method for tissue sampling for NGS.


Assuntos
Biópsia por Agulha , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias/genética , Adulto , Idoso , Biópsia , DNA/química , Estudos de Viabilidade , Feminino , Fluordesoxiglucose F18/química , Humanos , Biópsia Guiada por Imagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Agulhas , Neoplasias/metabolismo , Pelve/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
15.
Comput Methods Programs Biomed ; 175: 73-82, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104716

RESUMO

Medical image fusion is important in the field of clinical diagnosis because it can improve the availability of information contained in images. Magnetic Resonance Imaging (MRI) provides excellent anatomical details as well as functional information on regional changes in physiology, hemodynamics, and tissue composition. In contrast, although the spatial resolution of Positron Emission Tomography (PET) provides is lower than that an MRI, PET is capable of depicting the tissue's molecular and pathological activities that are not available from MRI. Fusion of MRI and PET may allow us to combine the advantages of both imaging modalities and achieve more precise localization and characterization of abnormalities. Previous image fusion algorithms, based on the estimation theory, assume that all distortions follow Gaussian distribution and are therefore susceptible to the model mismatch problem. To overcome this mismatch problem, we propose a new image fusion method with multi-resolution and nonparametric density models (MRNDM). The RGB space registered from the source multi-modal medical images is first transformed into a generalized intensity-hue-saturation space (GIHS), and then is decomposed into the low- and high-frequency components using the non-subsampled contourlet transform (NSCT). Two different fusion rules, which are based on the nonparametric density model and the theory of variable-weight, are developed and used to fuse low- and high-frequency coefficients. The fused images are constructed by performing the inverse of the NSCT operation with all composite coefficients. Our experimental results demonstrate that the quality of images fused from PET and MRI brain images using our proposed method MRNDM is higher than that of those fused using six previous fusion methods.


Assuntos
Encéfalo/diagnóstico por imagem , Imagem por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Algoritmos , Doença de Alzheimer/diagnóstico por imagem , Mapeamento Encefálico , Neoplasias Encefálicas/diagnóstico por imagem , Fluordesoxiglucose F18/química , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Distribuição Normal , Análise de Componente Principal
16.
J Vis Exp ; (146)2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30985755

RESUMO

In endothermic animals, brown adipose tissue (BAT) is activated to produce heat for defending body temperature in response to cold. BAT's ability to expend energy has made it a potential target for novel therapies to ameliorate obesity and associated metabolic disorders in humans. Though this tissue has been well studied in small animals, BAT's thermogenic capacity in humans remains largely unknown due to the difficulties of measuring its volume, activity, and distribution. Identifying and quantifying active human BAT is commonly performed using 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography and computed tomography (PET/CT) scans following cold-exposure or pharmacological activation. Here we describe a detailed image-analysis approach to quantify total-body human BAT from 18F-FDG PET/CT scans using an open-source software. We demonstrate the drawing of user-specified regions of interest to identify metabolically active adipose tissue while avoiding common non-BAT tissues, to measure BAT volume and activity, and to further characterize its anatomical distribution. Although this rigorous approach is time-consuming, we believe it will ultimately provide a foundation to develop future automated BAT quantification algorithms.


Assuntos
Tecido Adiposo Marrom/anatomia & histologia , Tecido Adiposo Marrom/diagnóstico por imagem , Fluordesoxiglucose F18/química , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Algoritmos , Humanos , Processamento de Imagem Assistida por Computador
17.
Bosn J Basic Med Sci ; 19(2): 195-200, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-30997878

RESUMO

In some non-small cell lung cancer (NSCLC) patients, lipid-poor adrenal adenomas cannot be adequately differentiated from metastases using imaging methods. Invasive diagnostic procedures also have a low negative predictive value (NPV) in such cases. The current study aims to establish a specific and clinically practical metabolic parameter for lipid-poor adrenal lesions (ALs) in NSCLC patients. This diagnostic approach may prevent unnecessary abdominal enhanced computed tomography (CT), magnetic resonance imaging, or invasive diagnostic procedures. Sixty-four NSCLC patients with 69 lipid-poor ALs and 28 control patients with 30 benign lipid-poor ALs, who underwent FDG-PET/CT, were retrospectively reviewed. Two morphological and four metabolic parameters were analyzed in FDG-PET/CT images of NSCLC and control patients. Baseline and post-chemotherapy images of 64 NSCLC patients were re-evaluated according to the PERCIST 1.0. In cases where ALs could not be differentiated, follow-up FDG-PET/CT images were re-examined. The receiver operating characteristic (ROC) curve method was used for the evaluation of diagnostic parameters. Out of 69 ALs, 39 were determined as metastatic lesions (adrenal metastasis), while 30 lesions were considered non-metastatic (adrenal adenomas). The mean attenuation value, SUVmax AL/SUVmax primary tumor, SUVmax, SUVmax AL/liver, and SUVmax AL/SUVmean liver were significantly different between metastatic and benign ALs from NSCLC patients. The SUVmax AL/SUVmean liver ≥1.81 had the best positive (PPV, 94.3%) and negative (NPV, 82.4%) predictive values, and the highest specificity (93.3%), sensitivity (84.6%) and accuracy (86.9%). Lipid-poor ALs with SUVmax AL/SUVmean liver ≥1.81 can be accepted as malignant in NSCLC. However, if SUVmax AL/SUVmean liver is <1.81, a pathologic examination is required. Utilizing this cut-off value to decide on adrenal core biopsy may prevent its unnecessary use. Moreover, this diagnostic approach can save time and reduce the healthcare costs.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/secundário , Idoso , Biópsia , Glicemia/análise , Linhagem Celular Tumoral , Feminino , Fluordesoxiglucose F18/química , Humanos , Lipídeos/química , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
18.
Mol Pharm ; 16(5): 2118-2128, 2019 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-30964298

RESUMO

Hypoxia imaging can guide tumor treatment and monitor changes in hypoxia during treatment. However, there is still no ideal hypoxia imaging agent for clinical applications. In this study, two novel 2-nitromidazole derivatives were synthesized and directly radiolabeled by [18F]FDG in high radiochemical yield and excellent radiochemical purity. Cell experiments, biodistribution, and positron emission tomography (PET) imaging studies were also conducted in mice-bearing S180 or OS732 tumors. [18F]FDG-2NNC2ON [(2 R,3 S,4 R, E)-2-18F-fluoro-3,4,5,6-tetrahydroxyhexanal O-3-(2-(2-nitro-1 H-imidazole-1-yl)ethylamino)-2-oxopropyl oxime] and [18F]FDG-2NNC5ON [(2 R,3 S,4 R, E)-2-18F-fluoro-3,4,5,6-tetrahydroxyhexanal-O-3-(5-(2-nitro-1 H-imidazole-1-yl)pentylamino)-2-oxopropyl oxime] can be cleared from the blood quickly and specifically target hypoxic tumor cells. The uptake of the probes by hypoxic cells gradually increases with time. After 4 h, the uptake value of [18F]FDG-2NNC2ON in hypoxic cells is 3.2 times higher than that in normoxia cells. In contrast, there is no difference in the uptake of [18F]FDG between hypoxic cells and normoxia cells. Biodistribution resulting from two tumor models indicate that the uptake values of the two radiotracers in the tumor are higher at 1 h than those at 2 and 4 h. At 1 and 2 h, the tumors are clearly observed on the PET images and the imaging features of [18F]FDG-2NNC5ON and [18F]FDG-2NNC2ON are distinct from those of [18F]FDG. Compared with [18F]FDG-2NNC5ON, [18F]FDG-2NNC2ON has a higher proportion of renal excretion, lower digestive tract uptake, and better imaging contrast because of its higher hydrophilicity. At 2 h, [18F]FDG-2NNC2ON shows a good tumor-to-blood (T/B) ratio, tumor-to-muscle ratio based on biodistribution (Bio-T/M ratio), and tumor-to-muscle ratio based on regions of interest on the PET images [region of interest (ROI)-T/M ratio] in the two tumor models (T/B, Bio-T/M, and ROI-T/M ratios are 3.2, 2.6, and 3.9 in the S180 tumor model and are 3.4, 4.2, and 4.6 in the OS732 tumor model, respectively). The imaging features visualized with autoradiography mostly coincided with the positive areas of HIF1α staining by immunofluorescence. Meanwhile, the biodistribution study and PET imaging revealed that the uptake of the radiotracers in the tumor cannot be competed by 5% glucose, confirming that [18F]FDG-2NNC2ON targets the hypoxic regions of the tumors instead of targeting tumors through the glucose metabolism pathway. These results suggest that the new 2-nitroimidazole derivative conjugated with [18F]FDG, [18F]FDG-2NNC2ON, has potential as an imaging agent for hypoxia.


Assuntos
Radioisótopos de Flúor/farmacocinética , Fluordesoxiglucose F18/farmacocinética , Nitroimidazóis/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Sarcoma 180/diagnóstico por imagem , Hipóxia Tumoral , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Radioisótopos de Flúor/química , Fluordesoxiglucose F18/química , Glucose/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nitroimidazóis/química , Compostos Radiofarmacêuticos/química , Eliminação Renal , Sarcoma 180/patologia , Distribuição Tecidual
19.
PLoS One ; 14(3): e0214299, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30921388

RESUMO

AIM: Characterizing tumor heterogeneity with textural indices extracted from 18F-fluorodeoxyglucose positron emission tomography (FDG PET/CT) is of growing interest in oncology. Several series showed promising results to predict survival in patients with head and neck squamous cell carcinoma (HNSCC), analyzing various tumor segmentation methods and textural indices. This preliminary study aimed at assessing the inter-observer and inter-segmentation method variability of textural indices in HNSCC pre-therapeutic FDG PET/CT. MATERIALS AND METHODS: Consecutive patients with HNSCC referred in our department for a pre-therapeutic FDG PET/CT from January to March 2016 were retrospectively included. Two nuclear medicine physicians separately segmented all tumors using 3 different segmentation methods: a relative standardized uptake value (SUV) threshold (40%SUVmax), a signal-to-noise adaptive SUV threshold (DAISNE) and an image gradient-based method (PET-EDGE). SUV and metabolic tumor volume were recorded. Thirty-one textural indices were calculated using LIFEx software (www.lifexsoft.org). After correlation analysis, selected indices' inter-segmentation method and inter-observer variability were calculated. RESULTS: Forty-three patients (mean age 63.8±9.3y) were analyzed. Due to a too small segmented tumor volume of interest, textural analysis could not be performed in 6, 11 and 15 cases with respectively DAISNE, 40%SUVmax and PET-EDGE segmentation methods. Five independent textural indices were selected (Homogeneity, Correlation, Entropy, Busyness and LZLGE). There was a high inter-contouring method variability for Homogeneity, Correlation, Entropy and LZLGE (p<0.0001 for each index). The inter-observer reproducibility analysis revealed an excellent agreement for 3 indices (Homogeneity, Correlation and Entropy) with an intraclass correlation coefficient higher than 0.90 for the 3 methods. CONCLUSIONS: This preliminary study showed a high variability of 4 out of 5 textural indices (Homogeneity, Correlation, Entropy and LZLGE) extracted from pre-therapeutic FDG PET/CT in HNSCC using 3 different contouring methods. However, for each method, there was an excellent agreement between observers for 3 of these textural indices (Homogeneity, Correlation and Entropy).


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Carcinoma de Células Escamosas/diagnóstico , Feminino , Fluordesoxiglucose F18/química , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Razão Sinal-Ruído , Software
20.
PLoS One ; 14(3): e0213202, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30889184

RESUMO

INTRODUCTION: Increasing evidence indicates that the development of type 2 diabetes is driven by chronic low grade beta-cell inflammation. However, it is unclear whether pancreatic inflammation can be noninvasively visualized in type 2 diabetes patients. We aimed to assess pancreatic 18F-FDG uptake in type 2 diabetes patients and controls using 18F-fluorodeoxylglucose positron emission tomography/computed tomography (18F-FDG PET/CT). MATERIAL AND METHODS: In this retrospective cross-sectional study, we enrolled 20 type 2 diabetes patients and 65 controls who had undergone a diagnostic 18F-FDG PET/CT scan and obtained standardized uptake values (SUVs) of pancreas and muscle. Pancreatic SUV was adjusted for background uptake in muscle and for fasting blood glucose concentrations. RESULTS: The maximum pancreatic SUVs adjusted for background muscle uptake (SUVmax.m) and fasting blood glucose concentration (SUVglucose) were significantly higher in diabetes patients compared to controls (median 2.86 [IQR 2.24-4.36] compared to 2.15 [IQR 1.51-2.83], p = 0.006 and median 2.76 [IQR 1.18-4.34] compared to 1.91 [IQR 1.27-2.55], p<0.001, respectively). In linear regression adjusting for age and body mass index, diabetes remained the main predictor of SUVmax.m and SUVglucose. CONCLUSION: Pancreatic 18F-FDG uptake adjusted for background muscle uptake and fasting blood glucose concentration was significantly increased in type 2 diabetes patients.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Fluordesoxiglucose F18/metabolismo , Pâncreas/metabolismo , Compostos Radiofarmacêuticos/metabolismo , Idoso , Glicemia/análise , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Fluordesoxiglucose F18/química , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Músculos/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/química , Estudos Retrospectivos
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