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1.
Abdom Radiol (NY) ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753211

RESUMO

PURPOSE: This study aimed to assess the predictive efficacy of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in parametrial invasion (PMI) in cervical cancer patients. METHODS: A total of 83 cervical cancer patients (32 PMI-positive and 51 PMI-negative) retrospectively underwent pretreatment IVIM-DWI and DCE-MRI scans. IVIM-DWI parameters included apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*), and perfusion fraction (f). DCE-MRI parameters included volume transfer constant (Ktrans), flux rate constant (Kep), and fractional extravascular extracellular space volume (Ve). Logistic regression analyses were conducted to identify independent variables associated with PMI. Receiver operating characteristic curves were generated to assess the predictive performance of significant parameters. RESULTS: Multivariable analysis revealed that the MRI parameters D (odds ratio [OR]: 7.05; 95% CI 1.78-27.88; P = 0.005), D* (OR 6.58; 95% CI 1.49-29.10; P = 0.01), f (OR 5.12; 95% CI 1.23-21.37; P = 0.03), Ktrans (OR 4.60; 95% CI 1.19-17.81; P = 0.03), and Kep (OR 4.90; 95% CI 1.25-19.18; P = 0.02) were independent predictors of PMI in cervical cancer patients. The combined parameter incorporating these parameters demonstrated the highest performance in predicting PMI, yielding an area under the curve of 0.906, sensitivity of 84.4%, and specificity of 86.3%. CONCLUSION: The proposed combined parameter exhibited favorable performance in identifying PMI in cervical cancer patients.

2.
J Magn Reson Imaging ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37929323

RESUMO

BACKGROUND: Due to their location and growth patterns, retroperitoneal tumors often involve the surrounding blood vessels. Clinical decisions on a proper treatment depend on the information on this condition. Evaluation of blood vessels using non-contrast-enhanced vessel wall MRI may provide noninvasive assessment of the extent of tumor invasion to assist clinical decision-making. PURPOSE: To investigate the performance and potential of non-contrast-enhanced vessel wall MRI in evaluating the degree of vessel wall invasion of retroperitoneal tumors. STUDY TYPE: Prospective. POPULATION: Thirty-seven participants (mean age: 60.59 ± 11.77 years, 59% male) with retroperitoneal tumors close to vessels based on their diagnostic computer tomography. FIELD STRENGTH/SEQUENCES: 3 T; vessel wall MRI sequences: two-dimensional T2-weighted MultiVane XD turbo spin-echo (2D-T2-MVXD-TSE) and three-dimensional T1-weighted motion sensitized driven equilibrium fat suppression turbo spin-echo (3D-T1-MSDE-TSE) sequences; conventional MRI sequences: T2-weighted fat suppression turbo spin-echo (T2-FS-TSE), T2-weighted turbo spin-echo (T2-TSE), modified Dixon T1-weighted fast field echo (T1-mDixon-FFE), and diffusion-weighted echo planar imaging (DWI-EPI) sequences. ASSESSMENT: All patients underwent preoperative imaging using both non-contrast conventional and vessel wall MRI sequences. Images obtained from conventional and vessel wall MRI sequences were evaluated independently by three junior radiologists (3 and 2 years of experience in reading MRI) and reviewed by one senior radiologist (25 years of experience in reading MRI) to assess the degree of vessel wall invasion. MRI were validated results from the clinical standard diagnosis based on surgical confirmation or histopathological reports. Interobserver agreement was determined based on the reports from three readers with similar years of experiences. Intraobserver variability was assessed based on categorizing and recategorizing the vessels of 37 patients 1 month apart. STATISTICAL TESTS: Intra-class correlation efficient (ICC), Chi-square test, McNemar test, area under the receiver-operating characteristic curve (AUC), Delong test, P < 0.05 was considered significant. RESULTS: The accuracy of vessel wall MRI (91.96%, 95% CI: 85.43-95.71; 103 of 112) in detecting the degree of vessel wall invasion was significantly higher than that of conventional MRI (75%, 95% CI: 66.24-82.10; 84 of 112). The interobserver variability or reproducibility in categorization of the degree of vascular wall invasion was good in evaluating images from conventional and vessel wall MRI sequences (ICC = 0.821, 95% CI: 0.765-0.867 and ICC = 0.881, 95% CI: 0.842-0.913, respectively). DATA CONCLUSION: Diagnosis of vessel wall invasion of retroperitoneal tumors and assessment of its severity can be improved by using non-contrast-enhanced vessel wall MRI. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

3.
Chem Biomed Imaging ; 1(2): 121-139, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37235188

RESUMO

Biomedical imaging, especially molecular imaging, has been a driving force in scientific discovery, technological innovation, and precision medicine in the past two decades. While substantial advances and discoveries in chemical biology have been made to develop molecular imaging probes and tracers, translating these exogenous agents to clinical application in precision medicine is a major challenge. Among the clinically accepted imaging modalities, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) exemplify the most effective and robust biomedical imaging tools. Both MRI and MRS enable a broad range of chemical, biological and clinical applications from determining molecular structures in biochemical analysis to imaging diagnosis and characterization of many diseases and image-guided interventions. Using chemical, biological, and nuclear magnetic resonance properties of specific endogenous metabolites and native MRI contrast-enhancing biomolecules, label-free molecular and cellular imaging with MRI can be achieved in biomedical research and clinical management of patients with various diseases. This review article outlines the chemical and biological bases of several label-free chemically and molecularly selective MRI and MRS methods that have been applied in imaging biomarker discovery, preclinical investigation, and image-guided clinical management. Examples are provided to demonstrate strategies for using endogenous probes to report the molecular, metabolic, physiological, and functional events and processes in living systems, including patients. Future perspectives on label-free molecular MRI and its challenges as well as potential solutions, including the use of rational design and engineered approaches to develop chemical and biological imaging probes to facilitate or combine with label-free molecular MRI, are discussed.

4.
Eur Radiol ; 33(4): 2561-2573, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36350393

RESUMO

OBJECTIVES: This study aims to investigate and develop imaging biomarkers for the diagnosis of cancer-associated cachexia based on the organ and tissue-specific abnormal metabolisms measured by fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT. METHODS: FDG PET/CT data from 390 cancer patients were analyzed retrospectively. Patients were divided into a development cohort and a validation cohort. Cachexia was defined as weight loss > 5% in 6 months or BMI < 20 and weight loss > 2%. According to the above definitions, patients were divided into cachexia and non-cachexia groups. Results of the clinical laboratory tests for metabolic levels and organ and tissue-specific FDG uptake obtained from the cachexia and non-cachexia groups were compared statistically. Logistic regression analysis was performed to identify independent variables associated with cachexia in the development cohort for generating the regression model. The performance of the model was tested using the data from a validation cohort and evaluated by area under the receiver operating characteristic curve (AUC). RESULTS: Based on the data from the development cohort of 286 patients and a validation cohort of 104 patients, it is found that age, white blood cell count, peak standardized uptake value (SUV) of the liver, and minimum SUV of lean body mass of visceral fat and subcutaneous fat were independently associated with cachexia. The model incorporating these variables reached an AUC of 0.777 (95% confidence interval (CI): 0.721, 0.833) in the development cohort and an AUC of 0.729 (95% CI: 0.629, 0.829) in the validation cohort. CONCLUSION: Organ and tissue-specific abnormal glucose metabolism as measured by PET/CT can be used as a biomarker for cancer-associated cachexia. KEY POINTS: • Patients with cancer-associated cachexia have reduced FDG uptake in the liver and increased FDG uptake in visceral fat and subcutaneous fat. • FDG uptake of the liver, visceral fat, and subcutaneous fat can be independent risk factors for identifying cancer-associated cachexia. • Cancer-associated cachexia can be classified using the model that incorporates age, white blood cell count, FDG uptake of the liver, and visceral and subcutaneous fat can diagnose with an AUC of 0.729.


Assuntos
Fluordesoxiglucose F18 , Neoplasias , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Neoplasias/complicações , Biomarcadores , Fígado , Obesidade , Redução de Peso
5.
Nutrients ; 14(15)2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35893867

RESUMO

BACKGROUND: Up to 80% of pancreatic cancer patients suffer from cachexia. White adipose tissue (WAT) browning caused by the tumorigenicity and progression aggravates the cancer-associated cachexia (CAC). Cancer-initiated changes in the protein-38 mitogen-activated protein kinases (p38 MAPK) pathway are likely involved in the development of CAC. METHODS: p38 MAPK inhibitors, VCP979 or SB203580, were used in the in vitro and in vivo models of pancreatic cancer cachexia. Expression of uncoupling protein 1 (UCP1) in the p38 MARK pathway and the properties and level of white adipocytes were analyzed and correlated to browning, followed by immunohistochemistry and Western blotting validations. Changes in the volume and fat fraction of WAT in animals were monitored by magnetic resonance imaging (MRI). RESULTS: The size of white adipocytes was increased after being treated with the p38 MAPK inhibitors, along with increase in the MRI-measured volume and fat fraction of WAT. Comparing two p38 MAPK inhibitors, the p38α subunit-specific inhibitor VCP979 had a better therapeutic effect than SB203580, which targets both p38α and ß subunits. CONCLUSIONS: Blockade of p38 MAPK reduced the WAT browning that contributes to CAC. Thus, p38 MARK inhibitors can potentially be used as a therapy for treating CAC. Non-invasive MRI can also be applied to assess the progression and treatment responses of CAC.


Assuntos
Proteína Quinase 14 Ativada por Mitógeno , Neoplasias Pancreáticas , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Caquexia/tratamento farmacológico , Caquexia/etiologia , Caquexia/metabolismo , Imageamento por Ressonância Magnética , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
J Clin Endocrinol Metab ; 107(4): e1699-e1709, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-34747996

RESUMO

CONTEXT: The current clinical methods for detecting skeletal muscle complications of type 2 diabetes mellitus (T2DM) are invasive and insensitive. There is an urgent need for noninvasive assessment of skeletal muscle microstructure changes during the disease progression and treatment to assist the clinical management. OBJECTIVE: This work aimed to investigate the T2DM caused changes in the fast-twitch tibialis anterior (TA) and slow-twitch soleus (SOL) skeletal muscles using T1ρ magnetic resonance imaging (MRI). METHODS: This cross-sectional study took place from December 2014 to December 2020 at Zhongda Hospital Southeast University. A total of 26 new-onset and 15 long-term T2DM patients were enrolled, with the addition of 20 young and 13 older healthy volunteers as age-matched controls. T1ρ relaxation times of SOL and TA muscles in different groups were measured. Parametric and nonparametric tests were used to analyze the relationship between the T1ρ values in SOL and TA muscles and the length of illness, level of fasting blood glucose, and status of homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: T1ρ relaxation times of SOL and TA muscles both of new-onset and long-term T2DM patients were significantly higher than those of the young (P < .01, P < .05) and older healthy controls (P < .05, P < .01). Positive correlations were observed between the T1ρ relaxation times of the TA or SOL and the duration of T2DM (R2 = 0.420, R2 = 0.326), the level of fasting blood glucose (R2 = 0.253, R2 = 0.071) and HOMA-IR (R2 = 0.232, R2 = 0.414). CONCLUSION: Quantitative MRI measurement of T1ρ provides a noninvasive tool to assess T2DM-induced changes in the skeletal muscles of T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2 , Glicemia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Humanos , Perna (Membro)/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia
7.
Exp Biol Med (Maywood) ; 246(14): 1597-1606, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33882700

RESUMO

This study aimed to track and evaluate the effect of low-dose irisin on the browning of white adipose tissue (WAT) in mice using magnetic resonance imaging (MRI) noninvasively in vivo. Mature white adipocytes extracted from mice were cultured, induced and characterized before being treated by irisin. The volume and fat fraction of WAT were quantified using MRI in normal chow diet and high fat mice after injection of irisin. The browning of cultured white adipocytes and WAT in mice were validated by immunohistochemistry and western blotting for uncoupling protein 1 (UCP1) and deiodinase type II (DIO2). The serum indexes were examined with high fat diet after irisin intervention. UCP1 and DIO2 in adipocytes showed increases responding to the irisin treatment. The size of white adipocytes in mice receiving irisin intervention was reduced. MRI measured volumes and fat fraction of WAT were significantly lower after Irisin treatment. Blood glucose and cholesterol levels were reduced in high fat diet mice after irisin treatment. Irisin intervention exerted browning of WAT, resulting reduction of volume and fat fraction of WAT as measured by MRI. Furthermore, it improved the condition of mice with diet-induced obesity and related metabolic disorders.


Assuntos
Adipócitos/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Fibronectinas/farmacologia , Adipócitos/metabolismo , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Branco/diagnóstico por imagem , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Dieta Hiperlipídica , Fibronectinas/metabolismo , Iodeto Peroxidase/metabolismo , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Desacopladora 1/metabolismo , Iodotironina Desiodinase Tipo II
8.
Int J Nanomedicine ; 13: 1819-1829, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29606873

RESUMO

BACKGROUND: Endothelial progenitor cells (EPCs) play an important role in repairing ischemia tissues. However, the survival, migration and therapeutic efficacy of EPCs after transplantation need to be better understood for further cell therapy. PURPOSE: This study investigated the migration effect of EPCs labeled with a multimodal imaging agent in a murine ischemic hindlimb model, using magnetic resonance imaging (MRI) and optical imaging after transplantation. METHODS: EPCs derived from mouse bone marrow were labeled with a multimodal imaging agent and were administered through intracardiac delivery to mice with ischemic hindlimbs. The injected EPCs and their migration effect were observed via MRI and optical imaging in vivo, and then compared to a reference standard based on histological data. The quantification of gadolinium in tissue samples was done using inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Using in vivo MRI and optical imaging, the labeled EPCs were observed to migrate to ischemic muscle on days 3-5 after injection, while ex vivo, the EPCs were observed in the capillary vessels of the injured tissue. There were significant linear correlations between the Gd contents measured using ICP-MS in samples from the ischemic hindlimbs and livers and T1 relaxation times calculated using MRI, as well as the average fluorescence signal intensities recorded in optical images (T1 relaxation time: r=0.491; average signal from optical imaging: r=0.704, P<0.01). EPC treatment upregulated the levels of C-X-C chemokine receptor 4 and vascular endothelial growth factor (VEGF) receptor 2 and enhanced the expression of stromal cell-derived factor-1 and VEGF. CONCLUSION: Transplanted EPCs can be monitored with noninvasive MRI and optical imaging in vivo and were found to enhance the paracrine secretion of angiogenic factors.


Assuntos
Movimento Celular , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/transplante , Isquemia/terapia , Imagem Multimodal , Músculos/irrigação sanguínea , Músculos/patologia , Animais , Células da Medula Óssea/citologia , Forma Celular , Terapia Baseada em Transplante de Células e Tecidos , Citosina Desaminase/metabolismo , Membro Posterior/irrigação sanguínea , Membro Posterior/patologia , Raios Infravermelhos , Isquemia/patologia , Fígado/patologia , Imageamento por Ressonância Magnética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Neovascularização Fisiológica , Imagem Óptica , Fenótipo , Polilisina/química
9.
Radiology ; 286(1): 129-139, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28777704

RESUMO

Purpose To test the feasibility of using blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging to measure alterations in renal oxygenation in a mouse model with experimental myocardial infarctions (MIs) of different sizes. Materials and Methods The study was approved by the local animal ethics committee. One hundred eighty-nine male C57BL/6 J mice were randomly subjected to MI surgery (with different locations of left anterior descending coronary artery occlusion) or sham surgery, defined as the exposure of the heart but no ligation. Mice with MI underwent late gadolinium enhancement imaging 1 day after occlusion to confirm infarct size. Mice were sorted into three groups: those with large MI (n = 48), those with small MI (n = 48), and those with sham operation (n = 36). Renal BOLD MR imaging was performed before and 1, 7, 14, 28, and 60 days after MI, and histologic analysis of renal hypoxia-inducible factor-1α (HIF-1α) and kidney injury molecule-1 (KIM-1) was performed to evaluate tissue hypoxia and kidney injury in subgroups imaged at each time point. The relationships between the BOLD R2* and HIF-1α expression and between HIF-1α and KIM-1 expression were assessed. Statistical analyses were performed with one-way analysis of variance or the Kruskal-Wallis test and Spearman correlation test. Results A significant elevation in R2* was detected in the MI groups compared with the sham group in the cortex (P < .001 for large MI vs sham group; P = .007 for small MI vs sham group) and medulla (P < .001 for large MI vs sham group; P = .003 for small MI vs sham group) on day 60, and R2* was higher in the large MI group than in the small MI group (P < .001). Renal HIF-1α expression was increased after MI and showed linear correlation with R2* in the cortex (R2 = 0.56) and medulla (R2 = 0.63). In addition, an increase in renal KIM-1 was observed in the MI groups compared with the sham group on day 60 (sham group, 53.9 × 103 arbitrary units [au] ± 35.2; large MI group, 389.3 × 103 au ± 99.8; and small MI group, 185.8 × 103 au ± 91.9; P < .001 for large MI group vs sham group; P = .037 for small MI group vs sham group), and renal KIM-1 showed a positive correlation with HIF-1α (R2 = 0.68). Conclusion The magnitude of renal hypoxia with MIs of different sizes can be noninvasively measured with BOLD MR imaging, and increased renal hypoxia is a potential risk factor for progressive tubulointerstitial injury in mouse kidneys. © RSNA, 2017 Online supplemental material is available for this article.


Assuntos
Isquemia/diagnóstico por imagem , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio/diagnóstico por imagem , Animais , Modelos Animais de Doenças , Coração/diagnóstico por imagem , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Oxigênio/sangue
10.
Colloids Surf B Biointerfaces ; 150: 261-270, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28029547

RESUMO

Detecting circulating tumor cells (CTCs) with high sensitivity and specificity is critical to management of metastatic cancers. Although immuno-magnetic technology for in vitro detection of CTCs has shown promising potential for clinical applications, the biofouling effect, i.e., non-specific adhesion of biomolecules and non-cancerous cells in complex biological samples to the surface of a device/probe, can reduce the sensitivity and specificity of cell detection. Reported herein is the application of anti-biofouling polyethylene glycol-block-allyl glycidyl ether copolymer (PEG-b-AGE) coated iron oxide nanoparticles (IONPs) to improve the separation of targeted tumor cells from aqueous phase in an external magnetic field. PEG-b-AGE coated IONPs conjugated with transferrin (Tf) exhibited significant anti-biofouling properties against non-specific protein adsorption and off-target cell uptake, thus substantially enhancing the ability to target and separate transferrin receptor (TfR) over-expressed D556 medulloblastoma cells. Tf conjugated PEG-b-AGE coated IONPs exhibited a high capture rate of targeted tumor cells (D556 medulloblastoma cell) in cell media (58.7±6.4%) when separating 100 targeted tumor cells from 1×105 non-targeted cells and 41 targeted tumor cells from 100 D556 medulloblastoma cells spiked into 1mL blood. It is demonstrated that developed nanoparticle has higher efficiency in capturing targeted cells than widely used micron-sized particles (i.e., Dynabeads®).


Assuntos
Incrustação Biológica , Compostos Férricos/química , Nanopartículas de Magnetita/química , Neoplasias/metabolismo , Polímeros/química , Adsorção , Animais , Biomarcadores/química , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Humanos , Ligantes , Luz , Macrófagos/metabolismo , Magnetismo , Camundongos , Microscopia de Fluorescência , Células Neoplásicas Circulantes , Polietilenoglicóis/química , Receptores da Transferrina/química , Sensibilidade e Especificidade , Propriedades de Superfície , Transferrina/química
11.
J Magn Reson Imaging ; 46(1): 61-70, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27862560

RESUMO

PURPOSE: To prospectively investigate age- and gender-related changes in the fast-twitch (tibialis anterior, TA) and slow-twitch (soleus, SOL) skeletal muscle of healthy rats and volunteers and to compare the exercise-related difference in health volunteers with T1 ρ magnetic resonance imaging (MRI). MATERIALS AND METHODS: In all, 18 rats and 70 humans were involved in this study. For the animal study, T1 ρ relaxation times were measured in the TA and SOL rat muscle with a 3.0T MRI scanner and compared to histological data. For the human study, three groups (young, middle-aged, and elderly) of volunteers underwent T1 ρ MRI scans (3.0T) of their calves. To further differentiate the human scans, 18 volunteers were recruited, half of them (n = 9) routinely trained with high-intensity sports, while the other half (n = 9) with no physical training. Statistical analysis was performed via paired t-test, independent-sample t-test, and analysis of variance (ANOVA). Correlations between T1 ρ and age/gender/physical endurance were calculated. RESULTS: The average T1 ρ relaxation times of the TA and SOL of female rats were higher than that of male rats (P < 0.001). The T1 ρ relaxation time of TA was significantly lower compared to SOL (P < 0.001). A significant linear correlation was observed between T1 ρ and the type I slow-twitch fiber proportion (%) in SOL (R2 = 0.837, P < 0.001). Similarly, in human studies the average T1 ρ relaxation times of TA were significantly lower than SOL for all age groups (P < 0.001). The higher T1 ρ relaxation times of TA and SOL in the elderly volunteers (P < 0.001) and in the females (P < 0.05) indicated significant age- and gender-dependent differences. In high-intensity sports groups, the higher T1 ρ in SOL (P < 0.01) and lower in TA (P < 0.05) were observed compared with the control group. CONCLUSION: This study demonstrated that T1 ρ MRI can be used to display the differences in fast- and slow-twitch skeletal muscle as well as potentially age-, gender-, and exercise-related differences. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:61-70.


Assuntos
Envelhecimento/fisiologia , Exercício Físico/fisiologia , Imageamento por Ressonância Magnética/métodos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Condicionamento Físico Humano/métodos , Adulto , Animais , Feminino , Humanos , Perna (Membro)/diagnóstico por imagem , Perna (Membro)/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Fatores Sexuais
12.
Stem Cells Int ; 2016: 3641401, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27656214

RESUMO

Endothelial progenitor cells (EPCs) play an important role in repairing ischemia tissues. Diffusion tensor imaging (DTI) was applied to detect the architectural organization of skeletal muscle. This study investigated the feasibility and accuracy of using the DTI to evaluate effectiveness of EPCs treatment. Mouse bone marrow-derived EPCs were isolated, cultured, characterized, and transplanted to hindlimb ischemia mice model. DTI was performed on the hindlimb at postischemia time points. The edema regions of diffusion restriction (high signal in diffusion weighted imaging) were decreased in the ischemic muscle of EPCs treated mice after 14 days compared with the controls. These results from DTI show the lower apparent diffusion coefficient and eigenvalues (λ1, λ2, and λ3) and the higher fractional anisotropy and fiber counts of ischemic muscle on 7 and 14 days after EPCs treatment compared to the controls. There was a significant correlation between fiber counts calculated by DTI and survival fibers evaluated by histological section (r = 0.873, P < 0.01). Our study demonstrated that the time frame for muscle fiber regeneration after EPCs transplantation was significantly shortened in vivo. DTI could be a useful tool for noninvasive evaluation of muscle tissue damage and repair in animal models and patient with ischemic diseases.

13.
Mol Med Rep ; 13(4): 3475-81, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26956080

RESUMO

Platelet­rich plasma (PRP) is a promising strategy for intervertebral disc degeneration (IDD). However, the short half­life of growth factors released from PRP cannot continuously stimulate the degenerated discs. Thus, the present study hypothesized that the combined use of PRP and bone marrow­derived mesenchymal stem cells (BMSCs) may repair the early degenerated discs in the long term for their synergistic reparative effect. In the present study, following the induction of early IDD by annular puncture in rabbits, PRP was prepared and mixed with BMSCs (PRP­BMSC group) for injection into the early degenerated discs. As controls, phosphate­buffered saline (PBS; PBS group) and PRP (PRP group) were similarly injected. Rabbits without any intervention served as a control group. At 8 weeks following treatment, histological changes of the injected discs were assessed. Magnetic resonance imaging (MRI) was used to detect the T2­weighted signal intensity of the targeted discs at weeks 1, 2 and 8 following treatment. Annular puncture resulted in disc narrowing and decreased T2­weighted signal intensity. At weeks 1 and 3, MRI examinations showed regenerative changes in the PRP­BMSC group and PRP group, whereas the PBS group exhibited a continuous degenerative process of the discs. At 8 weeks post­injection, the PRP­BMSCs induced a statistically significant restoration of discs, as shown by MRI (PRP­BMSCs, vs.PRP and PBS; P<0.05), which was also confirmed by histological evaluations. Thus, compared with PRP, the administration of PRP­containing BMSCs resulted in a superior regenerative effect on the early degenerated discs, which may be a promising therapeutic strategy for the restoration of early degenerated discs.


Assuntos
Degeneração do Disco Intervertebral/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Plasma Rico em Plaquetas , Animais , Células da Medula Óssea/citologia , Diferenciação Celular , Células Cultivadas , Colágeno Tipo II/metabolismo , Modelos Animais de Doenças , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Imageamento por Ressonância Magnética , Masculino , Células-Tronco Mesenquimais/metabolismo , Microscopia de Fluorescência , Coelhos
14.
CNS Neurosci Ther ; 21(11): 877-86, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26384586

RESUMO

AIMS: We tested the hypothesis that endothelial progenitor cell (EPC)-mediated functional recovery after stroke may be associated with the endothelial nitric oxide synthase (eNOS)/brain-derived neurotrophic factor (BDNF) signaling pathway. METHODS: Mice were infused with either EPCs or saline after being subjected to middle cerebral artery occlusion. The EPC-treated mice also received intravenous injections of either Nω-nitro-l-arginine methyl ester (L-NAME, the NOS inhibitor) or saline. RESULTS: The activation of eNOS and the expression of BDNF were significantly increased in ischemic brain of the EPC-treated mice, along with increased angiogenesis and neurogenesis. On diffusion tensor imaging (DTI), significant increases in fractional anisotropy and fiber count were observed in white matter, indicating axonal growth stimulated by EPCs. However, the EPC-treated mice that were received an L-NAME injection failed to exhibit the observed increases in angiogenesis, neurogenesis, and axonal growth. In addition, the neurons cocultured with EPCs in vitro exhibited the increased expression of BDNF and decreased apoptosis after oxygen-glucose deprivation compared with the control group. This EPC-induced protective effect was virtually absent in the L-NAME treatment group. CONCLUSION: The eNOS/BDNF pathway may be involved in the EPC-mediated functional recovery of stroke mice. DTI is feasible for dynamically tracking the orientation of axonal projections after EPC treatment.


Assuntos
Transplante de Medula Óssea/métodos , Células Progenitoras Endoteliais/fisiologia , Células Progenitoras Endoteliais/transplante , Infarto da Artéria Cerebral Média/cirurgia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células Cultivadas , Técnicas de Cocultura , Modelos Animais de Doenças , Inibidores Enzimáticos/uso terapêutico , Proteína Glial Fibrilar Ácida/metabolismo , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NG-Nitroarginina Metil Éster/uso terapêutico , Neovascularização Patológica/etiologia , Neovascularização Patológica/terapia , Doenças do Sistema Nervoso/etiologia , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Neurônios/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfopiruvato Hidratase/metabolismo , Fatores de Tempo
15.
Zhonghua Yi Xue Za Zhi ; 95(7): 537-40, 2015 Feb 17.
Artigo em Chinês | MEDLINE | ID: mdl-25916933

RESUMO

OBJECTIVE: To explore the correlation between liver T(2)(*) value and bone mineral density (BMD) in ovariectomized (OVX) rats. METHODS: A total of 60 rats, including sham (n = 25) and OVX (n = 35) groups, underwent dual-energy X-ray absorptiometry (DEXA) and liver magnetic resonance (MR)-T(2)(*) mapping for lumbar vertebra BMD and T(2)(*) values before and after operation monthly for 4 timepoints. Also micro-computed tomography (micro-CT) and biochemical measurements were performed. The sensitivity of liver T(2)(*) relaxation time detecting early osteoporosis were estimated and the correlation between liver T(2)(*) values and BMD analyzed. RESULTS: BMD of lumber vertebra in OVX group decreased compared to control group at Month 2 postoperation ((554 ± 27) mg/cm³ vs (722 ± 19) mg/cm³, P < 0.05) in synchrony with an elevation of serum ferritin concentration ((521 ± 41) ng/ml vs (441 ± 29) ng/ml, P < 0.01) and liver iron concentration ((291 ± 18) µg/g vs (237 ± 27) µg/g, P < 0.01). A significant inter-group difference of liver T(2)(*) was detected at Month 1 postoperation ((13.2 ± 0.7) ms vs (13.9 ± 0.4) ms, P < 0.01). Liver T(2)(*) was significant positively correlated with BMD in sham group (r = 0.410, P < 0.01) and OVX group (r = 0.434, P < 0.01). CONCLUSION: Liver T(2)(*) relaxation time may a valuable detection tool of assessing pathophysiological changes of osteoporosis in early stage.


Assuntos
Sobrecarga de Ferro , Osteoporose , Absorciometria de Fóton , Animais , Densidade Óssea , Feminino , Vértebras Lombares , Espectroscopia de Ressonância Magnética , Ovariectomia , Ratos , Coluna Vertebral , Tomografia Computadorizada por Raios X , Microtomografia por Raio-X
16.
Biomaterials ; 40: 43-50, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25433605

RESUMO

Endogenous endothelial progenitor cells (EPCs) are functionally impaired in hyperglycemia through the p38 MAPK signaling pathway. However, the number and function of transplanted exogenous EPCs in diabetic animals remains unclear. The objectives of this study were to establish a non-invasive imaging strategy to monitor the homing of transplanted EPCs in diabetic stroke mice and to assess the effect of RWJ 67657, an inhibitor of p38 MAPK, on the homing ability of exogenous EPCs. Bone marrow-derived EPCs were labeled in vitro with a multi-functional nanoprobe modified with paramagnetic chelators and fluorophores before being infused into stroke mice. The signal of the nanoprobe reached its peak on day 5 in both magnetic resonance imaging and near-infrared fluorescence imaging after EPC transplantation in wild-type stroke models. The signal enhancement of diabetic stroke models was significantly lower than that of wild-type controls. However, the signal intensity of diabetic stroke models significantly increased after oral administration of RWJ 67657, indicating that more transplanted EPCs migrated to the ischemic brain. Furthermore, the increased exogenous EPCs induced remarkably greater angiogenesis after stroke. These results suggest that this dual-modal imaging strategy is feasible for non-invasively monitoring transplanted cells in vivo.


Assuntos
Isquemia Encefálica/terapia , Diabetes Mellitus Experimental/terapia , Células Progenitoras Endoteliais/transplante , Acidente Vascular Cerebral/terapia , Animais , Isquemia Encefálica/complicações , Células Cultivadas , Diabetes Mellitus Experimental/complicações , Modelos Animais de Doenças , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Imidazóis/farmacologia , Imageamento por Ressonância Magnética , Masculino , Camundongos Endogâmicos C57BL , Nanopartículas/química , Neovascularização Fisiológica/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Piridinas/farmacologia , Coloração e Rotulagem , Acidente Vascular Cerebral/complicações , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Theranostics ; 4(8): 787-97, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24955140

RESUMO

PURPOSE: The efficacy of pro-angiogenic therapy is difficult to evaluate with current diagnostic modalities. The objectives were to develop a non-invasive imaging strategy to define the temporal characteristics of angiogenesis and to evaluate the response to pro-angiogenic therapy in diabetic stroke mouse models. METHODS: A home-made ανß3 integrin-targeted multi-modal nanoprobe was intravenously injected into mouse models at set time points after photothrombotic stroke. Magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging were carried out at 24 h post-injection. Bone marrow-derived endothelial progenitor cells (EPCs) were infused into the mouse models of ischemic stroke to stimulate angiogenesis. RESULTS: The peak signal intensity in the ischemic-angiogenic area of diabetic and wild-type mouse models was achieved on day 10, with significantly lower signal enhancement observed in the diabetic models. Although the signal intensity was significantly higher after EPC treatment in both models, the enhancement was less pronounced in the diabetic animals compared with the wild-type controls. Histological analysis revealed that the microvessel density and expression of ß3 integrin were correlated with the signal intensity assessed with MRI and NIRF imaging. CONCLUSIONS: The non-invasive imaging method could be used for early and accurate evaluation of the response to pro-angiogenic therapy in diabetic stroke models.


Assuntos
Indutores da Angiogênese/metabolismo , Complicações do Diabetes/terapia , Diagnóstico por Imagem/métodos , Nanopartículas , Neovascularização Fisiológica , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Animais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Endocitose/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Integrina alfaV/metabolismo , Integrina beta3/metabolismo , Imageamento por Ressonância Magnética , Masculino , Camundongos Endogâmicos C57BL , Microvasos/efeitos dos fármacos , Microvasos/patologia , Nanopartículas/química , Nanopartículas/toxicidade , Espectrometria de Fluorescência , Distribuição Tecidual/efeitos dos fármacos
18.
Eur Radiol ; 24(7): 1715-24, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24770554

RESUMO

OBJECTIVE: To explore the correlation between liver iron overload and bone mineral density (BMD) in an ovariectomy (OVX) rat model, using liver magnetic resonance (MR)-T2* and dual-energy X-ray absorptiometry (DEXA). METHODS: Sprague-Dawley rats received deferoxamine (DFO) or phosphate-buffered saline 3 months after bilateral OVX. MRI and DEXA were performed pre- and postoperatively. Five rats per group were killed every month for micro-CT, histopathology and biochemical examinations. Statistical analysis was performed with independent-samples t tests, box plots and Pearson's correlation analysis. RESULTS: At 2 months postoperatively, BMD was significantly lower in the OVX group than in the control group (P < 0.01), corresponding to the increased serum ferritin concentration (SFC; P < 0.01) and liver iron concentration (LIC; P < 0.01). Liver T2* values significantly differed between the two groups at 1 month postoperatively (P < 0.001) and improved 1 month after DFO injection (P < 0.05). These values were significantly and positively correlated with BMD in the control (r = 0.527, P < 0.001) and OVX (r = 0.456, P < 0.001) groups. CONCLUSION: Liver MRI T2* changed markedly earlier than BMD, LIC and SFC, and correlated well with osteoporosis; it may thus be a valuable early indicator of osteoporosis. KEY POINTS: • Iron overload plays a vital role in the pathogenesis of postmenopausal osteoporosis. • Liver T2* relaxation time is a sensitive value in reflecting iron overload. • Liver T2* mapping elucidates changes in postmenopausal osteoporosis earlier than BMD. • Iron chelation increases BMD in ovariectomized rats. • Liver T2* has a moderate positive correlation with BMD.


Assuntos
Sobrecarga de Ferro/diagnóstico , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Osteoporose Pós-Menopausa/diagnóstico , Absorciometria de Fóton , Animais , Densidade Óssea , Modelos Animais de Doenças , Feminino , Humanos , Ovariectomia , Ratos , Ratos Sprague-Dawley
19.
Radiology ; 269(3): 748-57, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23901127

RESUMO

PURPOSE: To determine the relationship between renal lipid content and intrarenal oxygenation in diabetic nephropathy by using noninvasive chemical shift-selective (CSS) imaging and blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study was approved by the institutional Committee on Animal Research. Lipid and water phantoms for CSS imaging were made, and BOLD MR imaging phantoms from arterial and venous blood samples were collected from rats. CSS imaging and BOLD imaging were performed to measure lipid contents and T2* in phantoms and kidneys of diabetic gene (db) db/db mice and wild-type mice after exposure to nitrogen (four per group) and injection of furosemide (four per group). Results of MR imaging-measured lipid contents and oxygen tension were compared with known values in phantoms and reference standard from mice with histologic data. Statistical analysis was performed with independent sample and paired sample t tests and Pearson correlation test. RESULTS: Renal lipid content in db/db mice was significantly higher compared with that in control mice (9.40% ± 1.89 and 3.11% ± 0.57, respectively; P < .001). In addition, the lipid content in the cortex of db/db mice was significantly higher than that in medulla (12.73% ± 0.94 and 3.16% ± 0.50, respectively; P < .001). Correlation was significant between T2* measured with BOLD and oxygen tension in blood phantoms (r = 0.958; P < .001). Lower baseline T2* in diabetic kidney suggested lower oxygenation that reserved excess oxygen supply. Lower oxygenation in diabetic kidney cortex was observed after nitrogen exposure and furosemide injection. CONCLUSION: Noninvasive CSS imaging and MR imaging of db/db diabetic mice revealed the relationship between the renal lipid content and intrarenal oxygenation in diabetic kidney. Lipid accumulation in diabetic kidney compromises the oxygenation of the renal tissue and made it more susceptible to renal hypoxia. Online supplemental material is available for this article.


Assuntos
Nefropatias Diabéticas/metabolismo , Rim/metabolismo , Metabolismo dos Lipídeos , Imageamento por Ressonância Magnética/métodos , Oxigênio/sangue , Animais , Diabetes Mellitus Experimental , Furosemida , Masculino , Camundongos , Imagens de Fantasmas
20.
Am J Physiol Endocrinol Metab ; 304(2): E160-7, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23149622

RESUMO

Brown adipose tissue (BAT) plays a key role in thermogenesis to protect the body from cold and obesity. White adipose tissue (WAT) stores excess energy in the form of triglycerides. To better understand the genetic effect on regulation of WAT and BAT, we investigated the fat fraction (FF) in two types of adipose tissues in ob/ob, human BSCL2/seipin gene knockout (SKO), Fsp27 gene knockout (Fsp27(-/-)), and wild-type (WT) mice in vivo using chemical shift selective imaging and (1)H-MR spectroscopy. We reported that the visceral fat volume in WAT was significantly larger in ob/ob mice, but visceral fat volumes were lower in SKO and Fsp27(-/-) mice compared with WT mice. BAT FF was significantly higher in ob/ob mice than the WT group and similar to that of WAT. In contrast, WAT FFs in SKO and Fsp27(-/-) mice were lower and similar to that of BAT. The adipocyte size of WAT in ob/ob mice and the BAT adipocyte size in ob/ob, SKO, and Fsp27 mice were significantly larger compared with WT mice. However, the WAT adipocyte size was significantly smaller in SKO mice than in WT mice. Positive correlations were observed between the adipocyte size and FFs of WAT and BAT. These results suggested that smaller adipocyte size correlates with lower FFs of WAT and BAT. In addition, the differences in FFs in WAT and BAT measured by MR methods in different mouse models were related to the different regulation effects of ob, seipin, or Fsp27 gene on developing WAT and BAT.


Assuntos
Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Branco/diagnóstico por imagem , Proteínas Heterotriméricas de Ligação ao GTP/genética , Leptina/genética , Proteínas/genética , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Animais , Distribuição da Gordura Corporal/métodos , Subunidades gama da Proteína de Ligação ao GTP , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Prótons , Radiografia
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