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1.
BMC Med Imaging ; 22(1): 5, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34986790

RESUMO

Pancreas volume is reduced in individuals with diabetes and in autoantibody positive individuals at high risk for developing type 1 diabetes (T1D). Studies investigating pancreas volume are underway to assess pancreas volume in large clinical databases and studies, but manual pancreas annotation is time-consuming and subjective, preventing extension to large studies and databases. This study develops deep learning for automated pancreas volume measurement in individuals with diabetes. A convolutional neural network was trained using manual pancreas annotation on 160 abdominal magnetic resonance imaging (MRI) scans from individuals with T1D, controls, or a combination thereof. Models trained using each cohort were then tested on scans of 25 individuals with T1D. Deep learning and manual segmentations of the pancreas displayed high overlap (Dice coefficient = 0.81) and excellent correlation of pancreas volume measurements (R2 = 0.94). Correlation was highest when training data included individuals both with and without T1D. The pancreas of individuals with T1D can be automatically segmented to measure pancreas volume. This algorithm can be applied to large imaging datasets to quantify the spectrum of human pancreas volume.

2.
PLoS Comput Biol ; 17(11): e1008845, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34843457

RESUMO

Hybrid multiscale agent-based models (ABMs) are unique in their ability to simulate individual cell interactions and microenvironmental dynamics. Unfortunately, the high computational cost of modeling individual cells, the inherent stochasticity of cell dynamics, and numerous model parameters are fundamental limitations of applying such models to predict tumor dynamics. To overcome these challenges, we have developed a coarse-grained two-scale ABM (cgABM) with a reduced parameter space that allows for an accurate and efficient calibration using a set of time-resolved microscopy measurements of cancer cells grown with different initial conditions. The multiscale model consists of a reaction-diffusion type model capturing the spatio-temporal evolution of glucose and growth factors in the tumor microenvironment (at tissue scale), coupled with a lattice-free ABM to simulate individual cell dynamics (at cellular scale). The experimental data consists of BT474 human breast carcinoma cells initialized with different glucose concentrations and tumor cell confluences. The confluence of live and dead cells was measured every three hours over four days. Given this model, we perform a time-dependent global sensitivity analysis to identify the relative importance of the model parameters. The subsequent cgABM is calibrated within a Bayesian framework to the experimental data to estimate model parameters, which are then used to predict the temporal evolution of the living and dead cell populations. To this end, a moment-based Bayesian inference is proposed to account for the stochasticity of the cgABM while quantifying uncertainties due to limited temporal observational data. The cgABM reduces the computational time of ABM simulations by 93% to 97% while staying within a 3% difference in prediction compared to ABM. Additionally, the cgABM can reliably predict the temporal evolution of breast cancer cells observed by the microscopy data with an average error and standard deviation for live and dead cells being 7.61±2.01 and 5.78±1.13, respectively.

3.
Breast Cancer Res ; 23(1): 110, 2021 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-34838096

RESUMO

BACKGROUND: The purpose of this study was to determine whether advanced quantitative magnetic resonance imaging (MRI) can be deployed outside of large, research-oriented academic hospitals and into community care settings to predict eventual pathological complete response (pCR) to neoadjuvant therapy (NAT) in patients with locally advanced breast cancer. METHODS: Patients with stage II/III breast cancer (N = 28) were enrolled in a multicenter study performed in community radiology settings. Dynamic contrast-enhanced (DCE) and diffusion-weighted (DW)-MRI data were acquired at four time points during the course of NAT. Estimates of the vascular perfusion and permeability, as assessed by the volume transfer rate (Ktrans) using the Patlak model, were generated from the DCE-MRI data while estimates of cell density, as assessed by the apparent diffusion coefficient (ADC), were calculated from DW-MRI data. Tumor volume was calculated using semi-automatic segmentation and combined with Ktrans and ADC to yield bulk tumor blood flow and cellularity, respectively. The percent change in quantitative parameters at each MRI scan was calculated and compared to pathological response at the time of surgery. The predictive accuracy of each MRI parameter at different time points was quantified using receiver operating characteristic curves. RESULTS: Tumor size and quantitative MRI parameters were similar at baseline between groups that achieved pCR (n = 8) and those that did not (n = 20). Patients achieving a pCR had a larger decline in volume and cellularity than those who did not achieve pCR after one cycle of NAT (p < 0.05). At the third and fourth MRI, changes in tumor volume, Ktrans, ADC, cellularity, and bulk tumor flow from baseline (pre-treatment) were all significantly greater (p < 0.05) in the cohort who achieved pCR compared to those patients with non-pCR. CONCLUSIONS: Quantitative analysis of DCE-MRI and DW-MRI can be implemented in the community care setting to accurately predict the response of breast cancer to NAT. Dissemination of quantitative MRI into the community setting allows for the incorporation of these parameters into the standard of care and increases the number of clinical community sites able to participate in novel drug trials that require quantitative MRI.

5.
Mol Imaging Biol ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611767

RESUMO

PURPOSE: The reprogramming of cellular metabolism is a hallmark of cancer. The ability to noninvasively assay glucose and lactate concentrations in cancer cells would improve our understanding of the dynamic changes in metabolic activity accompanying tumor initiation, progression, and response to therapy. Unfortunately, common approaches for measuring these nutrient levels are invasive or interrupt cell growth. This study transfected FRET reporters quantifying glucose and lactate concentration into breast cancer cell lines to study nutrient dynamics and response to therapy. PROCEDURES: Two FRET reporters, one assaying glucose concentration and one assaying lactate concentration, were stably transfected into the MDA-MB-231 breast cancer cell line. Correlation between FRET measurements and ligand concentration were measured using a confocal microscope and a cell imaging plate reader. Longitudinal changes in glucose and lactate concentration were measured in response to treatment with CoCl2, cytochalasin B, and phloretin which, respectively, induce hypoxia, block glucose uptake, and block glucose and lactate transport. RESULTS: The FRET ratio from the glucose and lactate reporters increased with increasing concentration of the corresponding ligand (p < 0.005 and p < 0.05, respectively). The FRET ratio from both reporters was found to decrease over time for high initial concentrations of the ligand (p < 0.01). Significant differences in the FRET ratio corresponding to metabolic inhibition were found when cells were treated with glucose/lactate transporter inhibitors. CONCLUSIONS: FRET reporters can track intracellular glucose and lactate dynamics in cancer cells, providing insight into tumor metabolism and response to therapy over time.

6.
Nat Protoc ; 16(11): 5309-5338, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34552262

RESUMO

This protocol describes a complete data acquisition, analysis and computational forecasting pipeline for employing quantitative MRI data to predict the response of locally advanced breast cancer to neoadjuvant therapy in a community-based care setting. The methodology has previously been successfully applied to a heterogeneous patient population. The protocol details how to acquire the necessary images followed by registration, segmentation, quantitative perfusion and diffusion analysis, model calibration, and prediction. The data collection portion of the protocol requires ~25 min of scanning, postprocessing requires 2-3 h, and the model calibration and prediction components require ~10 h per patient depending on tumor size. The response of individual breast cancer patients to neoadjuvant therapy is forecast by application of a biophysical, reaction-diffusion mathematical model to these data. Successful application of the protocol results in coregistered MRI data from at least two scan visits that quantifies an individual tumor's size, cellularity and vascular properties. This enables a spatially resolved prediction of how a particular patient's tumor will respond to therapy. Expertise in image acquisition and analysis, as well as the numerical solution of partial differential equations, is required to carry out this protocol.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética
7.
PLoS One ; 16(8): e0256029, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34428220

RESUMO

Magnetic resonance imaging (MRI) has detected changes in pancreas volume and other characteristics in type 1 and type 2 diabetes. However, differences in MRI technology and approaches across locations currently limit the incorporation of pancreas imaging into multisite trials. The purpose of this study was to develop a standardized MRI protocol for pancreas imaging and to define the reproducibility of these measurements. Calibrated phantoms with known MRI properties were imaged at five sites with differing MRI hardware and software to develop a harmonized MRI imaging protocol. Subsequently, five healthy volunteers underwent MRI at four sites using the harmonized protocol to assess pancreas size, shape, apparent diffusion coefficient (ADC), longitudinal relaxation time (T1), magnetization transfer ratio (MTR), and pancreas and hepatic fat fraction. Following harmonization, pancreas size, surface area to volume ratio, diffusion, and longitudinal relaxation time were reproducible, with coefficients of variation less than 10%. In contrast, non-standardized image processing led to greater variation in MRI measurements. By using a standardized MRI image acquisition and processing protocol, quantitative MRI of the pancreas performed at multiple locations can be incorporated into clinical trials comparing pancreas imaging measures and metabolic state in individuals with type 1 or type 2 diabetes.

8.
Tomography ; 7(3): 253-267, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201654

RESUMO

This study characterizes the error that results when performing quantitative analysis of abbreviated dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data of the breast with the Standard Kety-Tofts (SKT) model and its Patlak variant. More specifically, we used simulations and patient data to determine the accuracy with which abbreviated time course data could reproduce the pharmacokinetic parameters, Ktrans (volume transfer constant) and ve (extravascular/extracellular volume fraction), when compared to the full time course data. SKT analysis of simulated abbreviated time courses (ATCs) based on the imaging parameters from two available datasets (collected with a 3T MRI scanner) at a temporal resolution of 15 s (N = 15) and 7.23 s (N = 15) found a concordance correlation coefficient (CCC) greater than 0.80 for ATCs of length 3.0 and 2.5 min, respectively, for the Ktrans parameter. Analysis of the experimental data found that at least 90% of patients met this CCC cut-off of 0.80 for the ATCs of the aforementioned lengths. Patlak analysis of experimental data found that 80% of patients from the 15 s resolution dataset and 90% of patients from the 7.27 s resolution dataset met the 0.80 CCC cut-off for ATC lengths of 1.25 and 1.09 min, respectively. This study provides evidence for both the feasibility and potential utility of performing a quantitative analysis of abbreviated breast DCE-MRI in conjunction with acquisition of current standard-of-care high resolution scans without significant loss of information in the community setting.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste , Feminino , Humanos , Imageamento por Ressonância Magnética
9.
Eur J Radiol ; 136: 109534, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33454460

RESUMO

PURPOSE: This study assesses the rate of enhancement of breast fibroglandular tissue after administration of a magnetic resonance imaging (MRI) gadolinium-based contrast agent and determines its relationship with response to neoadjuvant therapy (NAT) in women with breast cancer. METHOD: Women with locally advanced breast cancer (N = 19) were imaged four times over the course of NAT. Dynamic contrast-enhanced (DCE) MRI was acquired after administration of a gadolinium-based contrast agent with a temporal resolution of 7.27 s. The tumor, fibroglandular tissue, and adipose tissue were semi-automatically segmented using a manually drawn region of interest encompassing the tumor followed by fuzzy c-means clustering. The rate and relative intensity of signal enhancement were calculated for each voxel within the tumor and fibroglandular tissue. RESULTS: The rate of fibroglandular tissue enhancement after contrast agent injection declined by an average of 29 % over the course of NAT. This decline was present in 16 of the 19 patients in the study. The rate of enhancement is significantly higher in women who achieve pathological complete response (pCR) after both 1 cycle (68 % higher, p < 0.05) and after 3-5 cycles of NAT (58 % higher; p < 0.05). The relative intensity of fibroglandular enhancement correlates with the rate of enhancement (R2 = 0.64, p < 0.001) and is higher in women who achieve pCR after both 1 cycle and after 3-5 cycles of NAT (p < 0.05, both timepoints). CONCLUSION: The rate of fibroglandular tissue enhancement declines over the course of therapy, provides novel information not reflected by tumoral measures, and may predict pathological response early in the course of therapy, with smaller declines in enhancement in women who achieve favorable response.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Meios de Contraste , Feminino , Humanos , Imageamento por Ressonância Magnética
10.
Front Endocrinol (Lausanne) ; 11: 592349, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343509

RESUMO

Magnetic resonance imaging (MRI) has the potential to improve our understanding of diabetes and improve both diagnosis and monitoring of the disease. Although the spatial resolution of MRI is insufficient to directly image the endocrine pancreas in people, the increasing awareness that the exocrine pancreas is also involved in diabetes pathogenesis has spurred new MRI applications. These techniques build upon studies of exocrine pancreatic diseases, for which MRI has already developed into a routine clinical tool for diagnosis and monitoring of pancreatic cancer and pancreatitis. By adjusting the imaging contrast and carefully controlling image acquisition and processing, MRI can quantify a variety of tissue pathologies. This review introduces a number of quantitative MRI techniques that have been applied to study the diabetic pancreas, summarizes progress in validating and standardizing each technique, and discusses the need for image analyses that account for spatial heterogeneity in the pancreas.


Assuntos
Diabetes Mellitus/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Neoplasias Pancreáticas/patologia , Pancreatite/patologia , Humanos
11.
Neoplasia ; 22(12): 820-830, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33197744

RESUMO

The ability to accurately predict response and then rigorously optimize a therapeutic regimen on a patient-specific basis, would transform oncology. Toward this end, we have developed an experimental-mathematical framework that integrates quantitative magnetic resonance imaging (MRI) data into a biophysical model to predict patient-specific treatment response of locally advanced breast cancer to neoadjuvant therapy. Diffusion-weighted and dynamic contrast-enhanced MRI data is collected prior to therapy, after 1 cycle of therapy, and at the completion of the first therapeutic regimen. The model is initialized and calibrated with the first 2 patient-specific MRI data sets to predict response at the third, which is then compared to patient outcomes (N = 18). The model's predictions for total cellularity, total volume, and the longest axis at the completion of the regimen are significant within expected measurement precision (P< 0.05) and strongly correlated with measured response (P < 0.01). Further, we use the model to investigate, in silico, a range of (practical) alternative treatment plans to achieve the greatest possible tumor control for each individual in a subgroup of patients (N = 13). The model identifies alternative dosing strategies predicted to achieve greater tumor control compared to the standard of care for 12 of 13 patients (P < 0.01). In summary, a predictive, mechanism-based mathematical model has demonstrated the ability to identify alternative treatment regimens that are forecasted to outperform the therapeutic regimens the patients clinically. This has important implications for clinical trial design with the opportunity to alter oncology care in the future.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Imageamento por Ressonância Magnética , Modelos Teóricos , Terapia Neoadjuvante , Medicina de Precisão , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Análise de Dados , Gerenciamento Clínico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Método de Monte Carlo , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Medicina de Precisão/métodos , Resultado do Tratamento
12.
J Clin Med ; 9(5)2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32370195

RESUMO

Optimal control theory is branch of mathematics that aims to optimize a solution to a dynamical system. While the concept of using optimal control theory to improve treatment regimens in oncology is not novel, many of the early applications of this mathematical technique were not designed to work with routinely available data or produce results that can eventually be translated to the clinical setting. The purpose of this review is to discuss clinically relevant considerations for formulating and solving optimal control problems for treating cancer patients. Our review focuses on two of the most widely used cancer treatments, radiation therapy and systemic therapy, as they naturally lend themselves to optimal control theory as a means to personalize therapeutic plans in a rigorous fashion. To provide context for optimal control theory to address either of these two modalities, we first discuss the major limitations and difficulties oncologists face when considering alternate regimens for their patients. We then provide a brief introduction to optimal control theory before formulating the optimal control problem in the context of radiation and systemic therapy. We also summarize examples from the literature that illustrate these concepts. Finally, we present both challenges and opportunities for dramatically improving patient outcomes via the integration of clinically relevant, patient-specific, mathematical models and optimal control theory.

13.
Sci Rep ; 10(1): 4767, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-32179809

RESUMO

Reduced pancreas volume, as measured by non-contrast magnetic resonance imaging (MRI), is observed in individuals with newly-diagnosed type 1 diabetes (T1D) and declines over the first year after diagnosis. In this study, we determined the repeatability and inter-reader reproducibility of pancreas volume measurements by MRI. Test-retest scans in individuals with or without T1D (n = 16) had an intraclass correlation coefficient (ICC) of 0.985 (95% CI 0.961 to 0.995) for pancreas volume. Independent pancreas outlines by two board-certified radiologists (n = 30) yielded an ICC of 0.945 (95% CI 0.889 to 0.973). The mean Dice coefficient, a measurement of the degree of overlap between pancreas regions of interest between the two readers, was 0.77. Prandial state did not influence pancreatic measurements, as stomach volume did not correlate with pancreas volume. These data demonstrate that MRI measurements of pancreas volume between two readers are repeatable and reproducible with ICCs that correspond to excellent clinical significance (ICC > 0.9), are not related to changes in stomach volume, and could be a useful tool for clinical investigation of diabetes and other pancreas pathologies.


Assuntos
Diabetes Mellitus Tipo 1/diagnóstico por imagem , Diabetes Mellitus Tipo 1/patologia , Imageamento por Ressonância Magnética/métodos , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Tamanho do Órgão , Reprodutibilidade dos Testes , Adulto Jovem
15.
Cancer ; 125(21): 3828-3835, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31328273

RESUMO

BACKGROUND: The incidence of colorectal cancer (CRC) in adults younger than 50 years has increased in the United States over the past decades according to Surveillance, Epidemiology, and End Results data. National guidelines conflict over beginning screening at the age of 45 or 50 years. METHODS: This was a retrospective study of National Cancer Data Base data from 2004 to 2015. The Cochran-Armitage test for trend was used to assess changes in the proportion of cases diagnosed at an age younger than 50 years. RESULTS: This study identified 130,165 patients diagnosed at an age younger than 50 years and 1,055,598 patients diagnosed at the age of 50 years or older. The proportion of the total number of patients diagnosed with CRC at an age younger than 50 years rose (12.2% in 2015 vs 10.0% in 2004; P < .0001). Younger adults presented with more advanced disease (stage III/IV; 51.6% vs 40.0% of those 50 years old or older). Among men, diagnosis at ages younger than 50 years rose only in non-Hispanic whites (P < .0001), whereas among women, Hispanic and non-Hispanic whites had increases in younger diagnoses over time (P < .05). All income quartiles had a proportional increase in younger adults over time (P < .001), with the highest income quartile having the highest proportion of younger cases. The proportion of younger onset CRC cases rose in urban areas (P < .001) but did not rise in rural areas. CONCLUSIONS: The proportion of persons diagnosed with CRC at an age younger than 50 years in the United States has continued to increase over the past decade, and younger adults present with more advanced disease. These data should be considered in the ongoing discussion of screening guidelines.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Programa de SEER/estatística & dados numéricos , Adulto , Fatores Etários , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etnologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia , /estatística & dados numéricos
16.
Tomography ; 5(1): 44-52, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30854441

RESUMO

Repeatability and reproducibility of magnetization transfer magnetic resonance imaging of the breast, and the ability of this technique to assess the response of locally advanced breast cancer to neoadjuvant therapy (NAT), are determined. Reproducibility scans at 3 different 3 T scanners, including 2 scanners in community imaging centers, found a 16.3% difference (n = 3) in magnetization transfer ratio (MTR) in healthy breast fibroglandular tissue. Repeatability scans (n = 10) found a difference of ∼8.1% in the MTR measurement of fibroglandular tissue between the 2 measurements. Thus, MTR is repeatable and reproducible in the breast and can be integrated into community imaging clinics. Serial magnetization transfer magnetic resonance imaging performed at longitudinal time points during NAT indicated no significant change in average tumoral MTR during treatment. However, histogram analysis indicated an increase in the dispersion of MTR values of the tumor during NAT, as quantified by higher standard deviation (P = .005), higher full width at half maximum (P = .02), and lower kurtosis (P = .02). Patients' stratification into those with pathological complete response (pCR; n = 6) at the conclusion of NAT and those with residual disease (n = 9) showed wider distribution of tumor MTR values in patients who achieved pCR after 2-4 cycles of NAT, as quantified by higher standard deviation (P = .02), higher full width at half maximum (P = .03), and lower kurtosis (P = .03). Thus, MTR can be used as an imaging metric to assess response to breast NAT.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Adulto , Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Centros Comunitários de Saúde , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasia Residual/patologia , Projetos Piloto , Reprodutibilidade dos Testes , Resultado do Tratamento
17.
J Magn Reson Imaging ; 50(5): 1377-1392, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30925001

RESUMO

The complexity of modern in vivo magnetic resonance imaging (MRI) methods in oncology has dramatically changed in the last 10 years. The field has long since moved passed its (unparalleled) ability to form images with exquisite soft-tissue contrast and morphology, allowing for the enhanced identification of primary tumors and metastatic disease. Currently, it is not uncommon to acquire images related to blood flow, cellularity, and macromolecular content in the clinical setting. The acquisition of images related to metabolism, hypoxia, pH, and tissue stiffness are also becoming common. All of these techniques have had some component of their invention, development, refinement, validation, and initial applications in the preclinical setting using in vivo animal models of cancer. In this review, we discuss the genesis of quantitative MRI methods that have been successfully translated from preclinical research and developed into clinical applications. These include methods that interrogate perfusion, diffusion, pH, hypoxia, macromolecular content, and tissue mechanical properties for improving detection, staging, and response monitoring of cancer. For each of these techniques, we summarize the 1) underlying biological mechanism(s); 2) preclinical applications; 3) available repeatability and reproducibility data; 4) clinical applications; and 5) limitations of the technique. We conclude with a discussion of lessons learned from translating MRI methods from the preclinical to clinical setting, and a presentation of four fundamental problems in cancer imaging that, if solved, would result in a profound improvement in the lives of oncology patients. Level of Evidence: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:1377-1392.


Assuntos
Imageamento por Ressonância Magnética/métodos , Oncologia/tendências , Neoplasias/diagnóstico por imagem , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Concentração de Íons de Hidrogênio , Hipóxia , Processamento de Imagem Assistida por Computador , Imunoterapia , Substâncias Macromoleculares , Metástase Neoplásica , Transplante de Neoplasias , Oxigênio/metabolismo , Reprodutibilidade dos Testes , Nanomedicina Teranóstica , /tendências
18.
Cell Metab ; 29(3): 745-754.e4, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30449685

RESUMO

Identification of cell-surface markers specific to human pancreatic ß cells would allow in vivo analysis and imaging. Here we introduce a biomarker, ectonucleoside triphosphate diphosphohydrolase-3 (NTPDase3), that is expressed on the cell surface of essentially all adult human ß cells, including those from individuals with type 1 or type 2 diabetes. NTPDase3 is expressed dynamically during postnatal human pancreas development, appearing first in acinar cells at birth, but several months later its expression declines in acinar cells while concurrently emerging in islet ß cells. Given its specificity and membrane localization, we utilized an NTPDase3 antibody for purification of live human ß cells as confirmed by transcriptional profiling, and, in addition, for in vivo imaging of transplanted human ß cells. Thus, NTPDase3 is a cell-surface biomarker of adult human ß cells, and the antibody directed to this protein should be a useful new reagent for ß cell sorting, in vivo imaging, and targeting.


Assuntos
Adenosina Trifosfatases/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Pâncreas/metabolismo , Adulto , Animais , Biomarcadores/metabolismo , Células Cultivadas , Humanos , Células Secretoras de Insulina/patologia , Ilhotas Pancreáticas/patologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Pâncreas/patologia , Adulto Jovem
19.
Diabetes Care ; 42(2): 248-257, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30552135

RESUMO

OBJECTIVE: This study investigated the temporal dynamics of pancreas volume and microstructure in children and adolescents with recent-onset type 1 diabetes (T1D) and individuals without diabetes, including a subset expressing autoantibodies associated with the early stages of T1D. RESEARCH DESIGN AND METHODS: MRI was performed in individuals with recent-onset stage 3 T1D (n = 51; median age 13 years) within 100 days after diagnosis (mean 67 days), 6 months, and 1 year postdiagnosis. Longitudinal MRI measurements were also made in similarly aged control participants (n = 57) and in autoantibody-positive individuals without diabetes (n = 20). The MRI protocol consisted of anatomical imaging to determine pancreas volume and quantitative MRI protocols interrogating tissue microstructure and composition. RESULTS: Within 100 days of diabetes onset, individuals with T1D had a smaller pancreas (median volume 28.6 mL) than control participants (median volume 48.4 mL; P < 0.001), including when normalized by individual weight (P < 0.001). Longitudinal measurements of pancreas volume increased in control participants over the year, consistent with adolescent growth, but pancreas volume declined over the first year after T1D diagnosis (P < 0.001). In multiple autoantibody-positive individuals, the pancreas volume was significantly larger than that of the T1D cohort (P = 0.017) but smaller than that of the control cohort (P = 0.04). Diffusion-weighted MRI showed that individuals with recent-onset T1D had a higher apparent diffusion coefficient (P = 0.012), suggesting a loss of cellular structural integrity, with heterogeneous pancreatic distribution. CONCLUSIONS: These results indicate that pancreas volume is decreased in stages 1, 2, and 3 of T1D and decreases during the first year after diabetes onset and that this loss of pancreatic volume is accompanied by microstructural changes.


Assuntos
Diabetes Mellitus Tipo 1/diagnóstico , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Adolescente , Adulto , Atrofia/diagnóstico , Atrofia/etiologia , Autoanticorpos/análise , Autoanticorpos/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/patologia , Feminino , Teste de Tolerância a Glucose , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Pâncreas/ultraestrutura , Fatores de Tempo , Adulto Jovem
20.
J Magn Reson Imaging ; 2018 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-29570895

RESUMO

BACKGROUND: Quantitative diffusion-weighted MRI (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) have the potential to impact patient care by providing noninvasive biological information in breast cancer. PURPOSE/HYPOTHESIS: To quantify the repeatability, reproducibility, and accuracy of apparent diffusion coefficient (ADC) and T1 -mapping of the breast in community radiology practices. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: Ice-water DW-MRI and T1 gel phantoms were used to assess accuracy. Normal subjects (n = 3) and phantoms across three sites (one academic, two community) were used to assess reproducibility. Test-retest analysis at one site in normal subjects (n = 12) was used to assess repeatability. FIELD STRENGTH/SEQUENCE: 3T Siemens Skyra MRI quantitative DW-MRI and T1 -mapping. ASSESSMENT: Quantitative DW-MRI and T1 -mapping parametric maps of phantoms and fibroglandular and adipose tissue of the breast. STATISTICAL TESTS: Average values of breast tissue were quantified and Bland-Altman analysis was performed to assess the repeatability of the MRI techniques, while the Friedman test assessed reproducibility. RESULTS: ADC measurements were reproducible across sites, with an average difference of 1.6% in an ice-water phantom and 7.0% in breast fibroglandular tissue. T1 measurements in gel phantoms had an average difference of 2.8% across three sites, whereas breast fibroglandular and adipose tissue had 8.4% and 7.5% average differences, respectively. In the repeatability study, we found no bias between first and second scanning sessions (P = 0.1). The difference between repeated measurements was independent of the mean for each MRI metric (P = 0.156, P = 0.862, P = 0.197 for ADC, T1 of fibroglandular tissue, and T1 of adipose tissue, respectively). DATA CONCLUSION: Community radiology practices can perform repeatable, reproducible, and accurate quantitative T1 -mapping and DW-MRI. This has the potential to dramatically expand the number of sites that can participate in multisite clinical trials and increase clinical translation of quantitative MRI techniques for cancer response assessment. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

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