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1.
AAPS PharmSciTech ; 22(3): 90, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33666763

RESUMEN

Contrast-enhanced X-ray computed tomography plays an important role in cancer imaging and disease progression monitoring. Imaging using radiopaque nanoparticle platforms can provide insights on the likelihood of nanoparticle accumulation and can enable image-guided therapies. Perfluorooctyl bromide (PFOB)-loaded nanocapsules designed for this purpose were stabilized using an in-house synthesized PEGylated polycaprolactone-based copolymer (PEG-b-PCL(Ch)) and compared with commercial polycaprolactone employing a Quality-by-Design approach. PFOB is a dense liquid, weakly polarizable, and immiscible in organic and aqueous solvents; thus, carefully designed formulations for optimal colloidal stabilization to overcome settling-associated instability are required. PFOB-loaded nanocapsules exhibited high PFOB loading due to the intrinsic properties of PEG-b-PCL(Ch). Settling and caking are major sources of instability for PFOB formulations. However, the PEG-b-PCL(Ch) copolymer conferred the nanocapsules enough steric impediment and polymer shell elasticity to settle without significant caking, increasing the overall colloidal stability of the formulation. Furthermore, a clear relationship between nanocapsule physical properties and X-ray attenuation was established. Nanocapsules were able to enhance the X-ray contrast in vitro as a function of PFOB loading. This nanocapsule-based platform is promising for future translational studies and image-guided tumor therapy due to its enhanced contrastability and optimal colloidal stability.


Asunto(s)
Medios de Contraste/administración & dosificación , Medios de Contraste/química , Tomografía Computarizada por Rayos X/métodos , Colesterol/química , Coloides , Composición de Medicamentos , Estabilidad de Medicamentos , Excipientes , Fluorocarburos , Hidrocarburos Bromados , Lactonas , Nanocápsulas , Tamaño de la Partícula , Fantasmas de Imagen , Polietilenglicoles
2.
Int J Mol Sci ; 22(4)2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33671448

RESUMEN

Ultrasound imaging is a widely used, readily accessible and safe imaging modality. Molecularly-targeted microbubble- and nanobubble-based contrast agents used in conjunction with ultrasound imaging expand the utility of this modality by specifically targeting and detecting biomarkers associated with different pathologies including cancer. In this study, nanobubbles directed to a cancer biomarker derived from the Receptor Protein Tyrosine Phosphatase mu, PTPmu, were evaluated alongside non-targeted nanobubbles using contrast enhanced ultrasound both in vitro and in vivo in mice. In vitro resonant mass and clinical ultrasound measurements showed gas-core, lipid-shelled nanobubbles conjugated to either a PTPmu-directed peptide or a Scrambled control peptide were equivalent. Mice with heterotopic human tumors expressing the PTPmu-biomarker were injected with PTPmu-targeted or control nanobubbles and dynamic contrast-enhanced ultrasound was performed. Tumor enhancement was more rapid and greater with PTPmu-targeted nanobubbles compared to the non-targeted control nanobubbles. Peak tumor enhancement by the PTPmu-targeted nanobubbles occurred within five minutes of contrast injection and was more than 35% higher than the Scrambled nanobubble signal for the subsequent two minutes. At later time points, the signal in tumors remained higher with PTPmu-targeted nanobubbles demonstrating that PTPmu-targeted nanobubbles recognize tumors using molecular ultrasound imaging and may be useful for diagnostic and therapeutic purposes.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Medios de Contraste/química , Imagen Molecular , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores/metabolismo , Ultrasonografía , Animales , Células Endoteliales/metabolismo , Femenino , Humanos , Riñón/metabolismo , Riñón/patología , Ratones Desnudos , Neoplasias/patología
3.
Nat Commun ; 12(1): 1682, 2021 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-33727562

RESUMEN

Functional intestinal imaging holds importance for the diagnosis and evaluation of treatment of gastrointestinal diseases. Currently, preclinical imaging of intestinal motility in animal models is performed either invasively with excised intestines or noninvasively under anesthesia, and cannot reveal intestinal dynamics in the awake condition. Capitalizing on near-infrared optics and a high-absorbing contrast agent, we report the Trans-illumination Intestine Projection (TIP) imaging system for free-moving mice. After a complete system evaluation, we performed in vivo studies, and obtained peristalsis and segmentation motor patterns of free-moving mice. We show the in vivo typical segmentation motor pattern, that was previously shown in ex vivo studies to be controlled by intestinal pacemaker cells. We also show the effects of anesthesia on motor patterns, highlighting the possibility to study the role of the extrinsic nervous system in controlling motor patterns, which requires unanesthetized live animals. Combining with light-field technologies, we further demonstrated 3D imaging of intestine in vivo (3D-TIP). Importantly, the added depth information allows us to extract intestines located away from the abdominal wall, and to quantify intestinal motor patterns along different directions. The TIP system should open up avenues for functional imaging of the GI tract in conscious animals in natural physiological states.


Asunto(s)
Motilidad Gastrointestinal/fisiología , Imagenología Tridimensional , Intestinos/diagnóstico por imagen , Intestinos/fisiología , Transiluminación , Anestesia , Animales , Medios de Contraste/química , Femenino , Cabello/diagnóstico por imagen , Humanos , Ratones , Movimiento , Factores de Tiempo
4.
Int J Nanomedicine ; 16: 2271-2282, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33776432

RESUMEN

Background: Contrast-enhanced magnetic resonance imaging (MRI) is a powerful diagnostic tool for many diseases. In many situations, the contrasts are repeatedly administrated in order to monitor and assess the disease progression. Objective: To investigate and compare the biological effects of γ-Fe2O3 nanoparticle (NP) and gadolinium dimeglumine (Gd-DTPA) with high and multiple doses on the kidney of healthy mice. Methods: Polydextrose sorbitol carboxymethyl ether coated γ-Fe2O3 NP with hydrodynamic size of 68.2 nm and clinically applied Gd-DTPA were employed on healthy mice with the repeatedly intravenous administration of high doses. The cell viability of human umbilical vein endothelial cells (HUVEC) in high doses of these two contrast agents were measured using the xCELLigence Real-Time Cell Analysis (RTCA) S16 Instrument. The biological effects of γ-Fe2O3 NP and Gd-DTPA on the kidney were obtained using a biochemical automatic analyzer and multiple proinflammatory factor kit on the serum. Histopathological and immunohistochemistry analysis were taken on kidney tissues. Results: It showed that the proinflammatory responses elicited by the γ-Fe2O3 NPs were weaker than that by Gd-DTPA, evidenced by the relatively much lower level of IL-1ß, IL-6, IL-18, TNF-α, C-reactive protein (CRP) and Ferritin. At the same time, the γ-Fe2O3 NPs did not have the biochemical index elevated, while the Gd-DTPA did. Conclusion: The γ-Fe2O3 NPs induced weaker proinflammatory effects in reference to the Gd-DTPA, indicating better renal safety. Therefore, it is suggested that γ-Fe2O3 NPs should be safer and optional choice when repeated contrast-enhanced MRI is necessary.


Asunto(s)
Medios de Contraste/química , Compuestos Férricos/química , Gadolinio DTPA/química , Inflamación/patología , Riñón/fisiopatología , Nanopartículas/química , Animales , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Proliferación Celular , Supervivencia Celular , Ferritinas/sangre , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Riñón/patología , Imagen por Resonancia Magnética , Masculino , Ratones , Espectrometría por Rayos X , Factor de Crecimiento Transformador beta/metabolismo
5.
Nat Biomed Eng ; 5(3): 252-263, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33686281

RESUMEN

Contrast agents for magnetic resonance imaging (MRI) improve anatomical visualizations. However, owing to poor image resolution in whole-body MRI, resolving fine structures is challenging. Here, we report that a nanoparticle with a polysaccharide supramolecular core and a shell of amorphous-like hydrous ferric oxide generating strong T1 MRI contrast (with a relaxivity coefficient ratio of ~1.2) facilitates the imaging, at resolutions of the order of a few hundred micrometres, of cerebral, coronary and peripheral microvessels in rodents and of lower-extremity vessels in rabbits. The nanoparticle can be synthesized at room temperature in aqueous solution and in the absence of surfactants, has blood circulation and renal clearance profiles that prevent opsonization, and leads to better imaging performance than Dotarem (gadoterate meglumine), a clinically approved gadolinium-based MRI contrast agent. The nanoparticle's biocompatibility and imaging performance may prove advantageous in a broad range of preclinical and clinical applications of MRI.


Asunto(s)
Dextranos/química , Compuestos Férricos/química , Imagen por Resonancia Magnética/métodos , Nanopartículas/química , Animales , Materiales Biocompatibles/química , Medios de Contraste/química , Gadolinio/química , Meglumina/química , Ratones , Ratones Endogámicos BALB C , Microvasos/patología , Compuestos Organometálicos/química , Tamaño de la Partícula , Polisacáridos/química , Conejos , Ratas , Ratas Sprague-Dawley
6.
Yonsei Med J ; 62(3): 200-208, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33635009

RESUMEN

PURPOSE: To compare image quality in selective intracoronary contrast-injected computed tomography angiography (Selective-CTA) with that in conventional intravenous contrast-injected CTA (IV-CTA). MATERIALS AND METHODS: Six pigs (35 to 40 kg) underwent both IV-CTA using an intravenous injection (60 mL) and Selective-CTA using an intracoronary injection (20 mL) through a guide-wire during/after percutaneous coronary intervention. Images of the common coronary artery were acquired. Scans were performed using a combined machine comprising an invasive coronary angiography suite and a 320-channel multi-slice CT scanner. Quantitative image quality parameters of CT attenuation, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), mean lumen diameter (MLD), and mean lumen area (MLA) were measured and compared. Qualitative analysis was performed using intraclass correlation coefficient (ICC), which was calculated for analysis of interobserver agreement. RESULTS: Quantitative image quality, determined by assessing the uniformity of CT attenuation (399.06 vs. 330.21, p<0.001), image noise (24.93 vs. 18.43, p<0.001), SNR (16.43 vs. 18.52, p=0.005), and CNR (11.56 vs. 13.46, p=0.002), differed significantly between IV-CTA and Selective-CTA. MLD and MLA showed no significant difference overall (2.38 vs. 2.44, p=0.068, 4.72 vs. 4.95, p=0.078). The density of contrast agent was significantly lower for selective-CTA (13.13 mg/mL) than for IV-CTA (400 mg/mL). Agreement between observers was acceptable (ICC=0.79±0.08). CONCLUSION: Our feasibility study in swine showed that compared to IV-CTA, Selective-CTA provides better image quality and requires less iodine contrast medium.


Asunto(s)
Angiografía por Tomografía Computarizada , Medios de Contraste/química , Angiografía Coronaria , Aumento de la Imagen , Animales , Vasos Coronarios , Estudios de Factibilidad , Femenino , Procesamiento de Imagen Asistido por Computador , Dosis de Radiación , Porcinos
7.
J Vis Exp ; (167)2021 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-33554963

RESUMEN

Efficient intracellular delivery of biomolecules is required for a broad range of biomedical research and cell-based therapeutic applications. Ultrasound-mediated sonoporation is an emerging technique for rapid intracellular delivery of biomolecules. Sonoporation occurs when cavitation of gas-filled microbubbles forms transient pores in nearby cell membranes, which enables rapid uptake of biomolecules from the surrounding fluid. Current techniques for in vitro sonoporation of cells in suspension are limited by slow throughput, variability in the ultrasound exposure conditions for each cell, and high cost. To address these limitations, a low-cost acoustofluidic device has been developed which integrates an ultrasound transducer in a PDMS-based fluidic device to induce consistent sonoporation of cells as they flow through the channels in combination with ultrasound contrast agents. The device is fabricated using standard photolithography techniques to produce the PDMS-based fluidic chip. An ultrasound piezo disk transducer is attached to the device and driven by a microcontroller. The assembly can be integrated inside a 3D-printed case for added protection. Cells and microbubbles are pushed through the device using a syringe pump or a peristaltic pump connected to PVC tubing. Enhanced delivery of biomolecules to human T cells and lung cancer cells is demonstrated with this acoustofluidic system. Compared to bulk treatment approaches, this acoustofluidic system increases throughput and reduces variability, which can improve cell processing methods for biomedical research applications and manufacturing of cell-based therapeutics.


Asunto(s)
Acústica/instrumentación , Células/metabolismo , Fluoresceína/metabolismo , Trehalosa/metabolismo , Células A549 , Células Cultivadas , Medios de Contraste/química , Humanos , Microburbujas , Linfocitos T/citología , Ultrasonido
8.
Korean J Radiol ; 22(4): 513-524, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33543842

RESUMEN

OBJECTIVE: To assess the noncontrast two-dimensional single-shot balanced turbo-field-echo magnetic resonance angiography (b-TFE MRA) features of the abdominal aortic aneurysm (AAA) status following endovascular aneurysm repair (EVAR) and evaluate to detect endoleaks (ELs). MATERIALS AND METHODS: We examined four aortic stent-grafts in a phantom study to assess the degree of metallic artifacts. We enrolled 46 EVAR-treated patients with AAA and/or common iliac artery aneurysm who underwent both computed tomography angiography (CTA) and b-TFE MRA after EVAR. Vascular measurements on CTA and b-TFE MRA were compared, and signal intensity ratios (SIRs) of the aneurysmal sac were correlated with the size changes in the AAA after EVAR (AAA prognoses). Furthermore, we examined six feasible b-TFE MRA features for the assessment of ELs. RESULTS: There were robust intermodality (r = 0.92-0.99) correlations and interobserver (intraclass correlation coefficient = 0.97-0.99) agreement. No significant differences were noted between SIRs and aneurysm prognoses. Moreover, "mottled high-intensity" and "creeping high-intensity with the low-band rim" were recognized as significant imaging findings suspicious for the presence of ELs (p < 0.001), whereas "no signal black spot" and "layered high-intensity area" were determined as significant for the absence of ELs (p < 0.03). Based on the two positive features, sensitivity, specificity, and accuracy for the detection of ELs were 77.3%, 91.7%, and 84.8%, respectively. Furthermore, the k values (0.40-0.88) displayed moderate-to-almost perfect agreement. CONCLUSION: Noncontrast MRA could be a promising imaging modality for ascertaining patient follow-up after EVAR.


Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Endofuga/diagnóstico por imagen , Angiografía por Resonancia Magnética , Anciano , Anciano de 80 o más Años , Implantación de Prótesis Vascular , Medios de Contraste/química , Endofuga/diagnóstico , Endofuga/etiología , Procedimientos Endovasculares , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Stents , Tomografía Computarizada por Rayos X
9.
PLoS One ; 16(1): e0244079, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33481820

RESUMEN

To assess the objective and subjective image quality, and respiratory motion of hepatocellular carcinoma with portal vein tumor thrombosis (PVTT) using the contrast-enhanced four-dimensional dual-energy computed tomography (CE-4D-DECT). For twelve patients, the virtual monochromatic image (VMI) derived from the CE-4D-DECT with the highest contrast to noise ratio (CNR) was determined as the optimal VMI (O-VMI). To assess the objective and subjective image quality, the CNR and five-point score of the O-VMI were compared to those of the standard VMI at 77 keV (S-VMI). The respiratory motion of the PVTT and diaphragm was measured based on the exhale and inhale phase images. The VMI at 60 keV yielded the highest CNR (4.8 ± 1.4) which was significantly higher (p = 0.02) than that in the S-VMI (3.8 ± 1.2). The overall image quality (4.0 ± 0.6 vs 3.1 ± 0.5) and tumor conspicuity (3.8 ± 0.8 vs 2.8 ± 0.6) of the O-VMI determined by three radiation oncologists was significantly higher (p < 0.01) than that of the S-VMI. The diaphragm motion in the L-R (3.3 ± 2.5 vs 1.2 ± 1.1 mm), A-P (6.7 ± 4.0 vs 1.6 ± 1.3mm) and 3D (8.8 ± 3.5 vs 13.1 ± 4.9 mm) directions were significantly larger (p < 0.05) compared to the tumor motion. The improvement of objective and subjective image quality was achieved in the O-VMI. Because the respiratory motion of the diaphragm was larger than that of the PVTT, we need to be pay attention for localizing target in radiotherapy.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Tomografía Computarizada Cuatridimensional , Interpretación de Imagen Asistida por Computador/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Trombosis/diagnóstico por imagen , Anciano , Carcinoma Hepatocelular/complicaciones , Medios de Contraste/química , Diafragma/diagnóstico por imagen , Diafragma/fisiología , Femenino , Humanos , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Vena Porta/diagnóstico por imagen , Vena Porta/patología , Estudios Retrospectivos , Relación Señal-Ruido , Trombosis/complicaciones
10.
Methods Mol Biol ; 2216: 205-227, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33476002

RESUMEN

Dynamic contrast-enhanced (DCE) MRI monitors the transit of contrast agents, typically gadolinium chelates, through the intrarenal regions, the renal cortex, the medulla, and the collecting system. In this way, DCE-MRI reveals the renal uptake and excretion of the contrast agent. An optimal DCE-MRI acquisition protocol involves finding a good compromise between whole-kidney coverage (i.e., 3D imaging), spatial and temporal resolution, and contrast resolution. By analyzing the enhancement of the renal tissues as a function of time, one can determine indirect measures of clinically important single-kidney parameters as the renal blood flow, glomerular filtration rate, and intrarenal blood volumes. Gadolinium-containing contrast agents may be nephrotoxic in patients suffering from severe renal dysfunction, but otherwise DCE-MRI is clearly useful for diagnosis of renal functions and for assessing treatment response and posttransplant rejection.Here we introduce the concept of renal DCE-MRI, describe the existing methods, and provide an overview of preclinical DCE-MRI applications to illustrate the utility of this technique to measure renal perfusion and glomerular filtration rate in animal models.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction is complemented by two separate publications describing the experimental procedure and data analysis.


Asunto(s)
Biomarcadores/análisis , Medios de Contraste/química , Imagen de Difusión por Resonancia Magnética/métodos , Tasa de Filtración Glomerular , Aumento de la Imagen/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Riñón/fisiología , Animales , Humanos , Monitoreo Fisiológico/métodos , Perfusión , Circulación Renal , Programas Informáticos
11.
Methods Mol Biol ; 2216: 229-239, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33476003

RESUMEN

The kidney is a complex organ involved in the excretion of metabolic products as well as the regulation of body fluids, osmolarity, and homeostatic status. These functions are influenced in large part by alterations in the regional distribution of blood flow between the renal cortex and medulla. Renal perfusion is therefore a key determinant of glomerular filtration. Therefore the quantification of regional renal perfusion could provide important insights into renal function and renal (patho)physiology. Arterial spin labeling (ASL) based perfusion MRI techniques, can offer a noninvasive and reproducible way of measuring renal perfusion in animal models. This chapter addresses the basic concept of ASL-MRI.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.


Asunto(s)
Biomarcadores/análisis , Medios de Contraste/química , Imagen de Difusión por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Riñón/fisiología , Circulación Renal , Marcadores de Spin , Animales , Arterias , Velocidad del Flujo Sanguíneo , Humanos , Aumento de la Imagen/métodos , Riñón/irrigación sanguínea , Monitoreo Fisiológico/métodos , Perfusión , Programas Informáticos
12.
Methods Mol Biol ; 2216: 241-256, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33476004

RESUMEN

Magnetic Resonance Imaging (MRI) has been actively explored in the last several decades for assessing renal function by providing several physiological information, including glomerular filtration rate, renal plasma flow, tissue oxygenation and water diffusion. Within MRI, the developing field of chemical exchange saturation transfer (CEST) has potential to provide further functional information for diagnosing kidney diseases. Both endogenous produced molecules as well as exogenously administered CEST agents have been exploited for providing functional information related to kidney diseases in preclinical studies. In particular, CEST MRI has been exploited for assessing the acid-base homeostasis in the kidney and for monitoring pH changes in several disease models. This review summarizes several CEST MRI procedures for assessing kidney functionality and pH, for monitoring renal pH changes in different kidney injury models and for evaluating renal allograft rejection.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.


Asunto(s)
Biomarcadores/análisis , Medios de Contraste/química , Procesamiento de Imagen Asistido por Computador/métodos , Riñón/fisiología , Imagen por Resonancia Magnética/métodos , Monitoreo Fisiológico/métodos , Fantasmas de Imagen , Animales , Humanos , Concentración de Iones de Hidrógeno , Programas Informáticos
13.
Methods Mol Biol ; 2216: 455-471, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33476017

RESUMEN

Chemical exchange saturation transfer (CEST) is recognized as one of the premier methods for measuring pH with this environmental variable expected to be an excellent biomarker for kidney diseases. Here we describe step-by-step CEST MRI experimental protocols for producing pH and perfusion maps for monitoring kidney pH homeostasis in rodents after administering iopamidol as contrast agent. Several CEST techniques, acquisition protocols and ratiometric approaches are described. The impact of length of acquisition time on the quality of the maps is detailed. These methods may be useful for investigating progression in kidney disease in vivo for rodent models.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol is complemented by two separate chapters describing the basic concepts and data analysis.


Asunto(s)
Medios de Contraste/química , Procesamiento de Imagen Asistido por Computador/métodos , Riñón/fisiología , Imagen por Resonancia Magnética/métodos , Monitoreo Fisiológico/métodos , Fantasmas de Imagen , Animales , Concentración de Iones de Hidrógeno , Ratones , Ratones Endogámicos C57BL , Programas Informáticos
14.
Methods Mol Biol ; 2216: 591-610, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33476026

RESUMEN

Renal hypoxia is generally accepted as a key pathophysiologic event in acute kidney injury of various origins and has also been suggested to play a role in the development of chronic kidney disease. Here we describe step-by-step data analysis protocols for MRI monitoring of renal oxygenation in rodents via the deoxyhemoglobin concentration sensitive MR parameters T2* and T2-a contrast mechanism known as the blood oxygenation level dependent (BOLD) effect.This chapter describes how to use the analysis tools provided by vendors of animal and clinical MR systems, as well as how to develop an analysis software. Aspects covered are: data quality checks, data exclusion, model fitting, fitting algorithm, starting values, effects of multiecho imaging, and result validation.This chapter is based upon work from the PARENCHIMA COST Action, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by two separate chapters describing the basic concept and data analysis.


Asunto(s)
Biomarcadores/análisis , Medios de Contraste/química , Procesamiento de Imagen Asistido por Computador/métodos , Riñón/fisiología , Imagen por Resonancia Magnética/métodos , Monitoreo Fisiológico/métodos , Oxígeno/sangre , Algoritmos , Animales , Consumo de Oxígeno , Programas Informáticos
15.
Methods Mol Biol ; 2216: 637-653, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33476028

RESUMEN

Here we present an analysis protocol for dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data of the kidneys. It covers comprehensive steps to facilitate signal to contrast agent concentration mapping via T1 mapping and the calculation of renal perfusion and filtration parametric maps using model-free approaches, model free analysis using deconvolution, the Toft's model and a Bayesian approach.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.


Asunto(s)
Algoritmos , Medios de Contraste/química , Tasa de Filtración Glomerular , Procesamiento de Imagen Asistido por Computador/métodos , Riñón/fisiología , Imagen por Resonancia Magnética/métodos , Circulación Renal , Animales , Aumento de la Imagen , Riñón/irrigación sanguínea , Monitoreo Fisiológico , Perfusión , Programas Informáticos
16.
Methods Mol Biol ; 2216: 689-696, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33476031

RESUMEN

The signal acquired in sodium (23Na) MR imaging is proportional to the concentration of sodium in a voxel, and it is possible to convert between the two using external calibration phantoms. Postprocessing, and subsequent analysis, of sodium renal images is a simple task that can be performed with readily available software. Here we describe the process of conversion between sodium signal and concentration, estimation of the corticomedullary sodium gradient and the procedure used for quadrupolar relaxation analysis.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.


Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Riñón/fisiología , Imagen por Resonancia Magnética/métodos , Monitoreo Fisiológico/métodos , Fantasmas de Imagen , Isótopos de Sodio/análisis , Animales , Medios de Contraste/química , Imagenología Tridimensional , Ratas , Programas Informáticos
17.
Methods Mol Biol ; 2216: 667-688, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33476030

RESUMEN

The kidney plays a major role in maintaining body pH homeostasis. Renal pH, in particular, changes immediately following injuries such as intoxication and ischemia, making pH an early biomarker for kidney injury before the symptom onset and complementary to well-established laboratory tests. Because of this, it is imperative to develop minimally invasive renal pH imaging exams and test pH as a new diagnostic biomarker in animal models of kidney injury before clinical translation. Briefly, iodinated contrast agents approved by the US Food and Drug Administration (FDA) for computed tomography (CT) have demonstrated promise as novel chemical exchange saturation transfer (CEST) MRI agents for pH-sensitive imaging. The generalized ratiometric iopamidol CEST MRI analysis enables concentration-independent pH measurement, which simplifies in vivo renal pH mapping. This chapter describes quantitative CEST MRI analysis for preclinical renal pH mapping, and their application in rodents, including normal conditions and acute kidney injury.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concepts and experimental procedure.


Asunto(s)
Medios de Contraste/química , Procesamiento de Imagen Asistido por Computador/métodos , Riñón/fisiología , Imagen por Resonancia Magnética/métodos , Monitoreo Fisiológico/métodos , Fantasmas de Imagen , Animales , Concentración de Iones de Hidrógeno , Programas Informáticos
18.
Int J Nanomedicine ; 16: 201-211, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33447035

RESUMEN

Objective: PEGylated superparamagnetic iron oxide (SPIO) is the most promising alternatives to gadolinium-based contrast agents (GBCAs) in MRI. This paper is to explore the imaging effects of PEGylated SPIO, which is influenced by particle sizes and surface polyethylene glycol (PEG) coating, using as MRI contrast agents at different magnetic field intensities. Methods: Firstly, nine PEGylated monocrystalline SPIO nanoparticles with different nanocrystal sizes and different molecular weights PEG coating were prepared, and then physical and biological properties were analyzed. Finally, MRI imaging in vivo was performed to observe the imaging performance. Results: Nine PEGylated monocrystalline SPIO nanoparticles have good relaxivities, serum stability, and biosecurity. At the same time, they show different imaging characteristics at different magnetic field intensities. Eight-nanometer SPIO@PEG5k is an effective T 2 contrast agent at 3.0 T (r 2/r 1 = 14.0), is an ideal T 1-T 2 dual-mode contrast agent at 1.5 T (r 2/r 1 = 6.52), and is also an effective T 1 contrast agent at 0.5 T (r 2/r 1 = 2.49), while 4-nm SPIO@PEG5k is a T 1-T 2 dual-mode contrast agent at 3.0 T (r 2/r 1 = 5.24), and is a useful T 1 contrast agent at 0.5 T (r 2/r 1 = 1.74) and 1.5 T (r 2/r 1 = 2.85). MRI studies in vivo at 3.0 T further confirm that 4-nm SPIO@PEG5k displays excellent T 1-T 2 dual-mode contrast enhancement, whereas 8-nm SPIO@PEG5k only displays T 2 contrast enhancement. Conclusion: PEGylated SPIOs with different nanocrystal sizes and PEG coating can be used as T 1, T 2, or T 1-T 2 dual-mode contrast agents to meet the clinical demands of MRI at specific magnetic fields.


Asunto(s)
Medios de Contraste/química , Imagen por Resonancia Magnética , Nanocompuestos/química , Polietilenglicoles/química , Animales , Campos Magnéticos , Masculino , Ratones , Nanocompuestos/ultraestructura , Nanopartículas/química , Nanopartículas/ultraestructura , Tamaño de la Partícula , Células RAW 264.7 , Ratas Sprague-Dawley , Suero/metabolismo
19.
Nat Commun ; 12(1): 34, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397947

RESUMEN

Colloidal gold nanoparticles (GNPs) serve as promising contrast agents in photoacoustic (PA) imaging, yet their utility is limited due to their absorption peak in the visible window overlapping with that of hemoglobin. To overcome such limitation, this report describes an ultrapure chain-like gold nanoparticle (CGNP) clusters with a redshift peak wavelength at 650 nm. The synthesized CGNP show an excellent biocompatibility and photostability. These nanoparticles are conjugated with arginine-glycine-aspartic acid (RGD) peptides (CGNP clusters-RGD) and validated in 12 living rabbits to perform multimodal photoacoustic microscopy (PAM) and optical coherence tomography (OCT) for visualization of newly developed blood vessels in the sub-retinal pigment epithelium (RPE) space of the retina, named choroidal neovascularization (CNV). The PAM system can achieve a 3D PAM image via a raster scan of 256 × 256 pixels within a time duration of 65 s. Intravenous injection of CGNP clusters-RGD bound to CNV and resulted in up to a 17-fold increase in PAM signal and 176% increase in OCT signal. Histology indicates that CGNP clusters could disassemble, which may facilitate its clearance from the body.


Asunto(s)
Oro/química , Nanopartículas del Metal/química , Microscopía , Imagen Molecular , Técnicas Fotoacústicas , Tomografía de Coherencia Óptica , Animales , Neovascularización Coroidal/diagnóstico por imagen , Neovascularización Coroidal/patología , Medios de Contraste/química , Femenino , Pruebas de Función Renal , Pruebas de Función Hepática , Masculino , Nanopartículas del Metal/ultraestructura , Ratones , Oligopéptidos/química , Conejos , Distribución Tisular
20.
Angew Chem Int Ed Engl ; 60(8): 3923-3927, 2021 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-33325142

RESUMEN

Olsalazine (Olsa) is a broad-spectrum anti-cancer agent acting as a DNA-methylation inhibitor. When conjugated to 2-cyano-6-aminobenzothiazole and a peptide substrate specific for the tumor-overexpressed enzyme furin, it can self-assemble into nanoparticles that can be detected by chemical-exchange saturation-transfer magnetic-resonance imaging (CEST MRI). We report here that these nano-assemblies can also be detected with high specificity in furin-overexpressing tumor cells by Raman spectroscopy with a distinct scattering signature and demonstrate the utility of this sensing mechanism in vitro and in vivo. Our findings suggest that Raman spectroscopy could be used for high-resolution image-guided surgery to precisely delineate tumor margins during and after resection in real-time as well as to determine microscopic tumor invasion and multifocal locoregional tumor spread, which are currently impossible to visualize with available imaging technologies, including CEST MRI.


Asunto(s)
Ácidos Aminosalicílicos/química , Imagen por Resonancia Magnética/métodos , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Animales , Medios de Contraste/química , Células HCT116 , Humanos , Ratones , Ratones SCID , Microscopía Fluorescente , Neoplasias/patología , Espectrometría Raman , Trasplante Heterólogo
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