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1.
Acta Biomater ; 130: 473-484, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34082102

RESUMEN

Transdermal delivery is an attractive strategy for treating superficial tumors. However, the applications of existing transdermal systems have been limited by low transdermal efficiency and poor therapeutic outcomes. Here, we develop a transdermal nanoplatform (+)T-SiDs, based on superparamagnetic iron oxide core, surface-modified with cationic lipids, transdermal enhanced peptide TD, and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR), and loaded with doxorubicin. The (+)T-SiDs compositions enable MR/NIR dual-modal imaging guided synergistic chemo-photothermal therapy to superficial tumors treatment via transdermal delivery. The (+)T-SiDs exhibit good stability, efficient cellular uptake, pH/photothermal responsive drug release, and high photothermal conversion efficiency (47.45%). Importantly, the transdermal delivery of (+)T-SiDs is significantly enhanced by TD functionalization. In vivo MR/NIR imaging shows that the (+)T-SiDs exhibit high transdermal efficiency and specificity in localization to the tumor site. Moreover, in comparison with individual chemo- or photothermal therapies, the combination of chemo-photothermal therapy exhibits more efficient tumor inhibition effects. This work presents a new transdermal treatment nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors, with efficient tumor eradication and low systemic toxicity thus offering strong potential for clinical adoption. STATEMENT OF SIGNIFICANCE: Transdermal delivery is an attractive strategy for treating superficial tumors. However, a highly efficient transdermal nanoplatform remains to be developed. Herein, we designed a multifunctional transdermal nanoplatform for dual-modal imaging-guided chemo-photothermal therapy of superficial tumors, comprised of a super-paramagnetic iron oxide (SPIO) nanoparticle, which can act as an MRI contrast agent and photothermal agent; a transdermal enhanced peptide (TD) and cationic lipids, which can accelerate skin penetration; and a NIR dye (DiR) and doxorubicin (DOX), which can achieve a synergistic enhanced chemo-photothermal therapy with NIR imaging ability. The transdermal nanoplatform achieved efficient tumor eradication and low systemic toxicity, thus offering strong potential for clinical adoption.


Asunto(s)
Hipertermia Inducida , Nanopartículas , Neoplasias , Animales , Doxorrubicina/farmacología , Nanopartículas Magnéticas de Óxido de Hierro , Ratones , Ratones Endogámicos BALB C , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Fototerapia , Terapia Fototérmica
2.
J Mater Chem B ; 9(24): 4846-4856, 2021 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-34047333

RESUMEN

Psoriasis is one of the most influential and fastest-growing inflammatory diseases of the skin. Curcumin (CRC) is an effective antipsoriatic drug that is often carried by nanoparticles or liposomes mainly administered via the skin. However, the therapeutic effectiveness and bioavailability of this drug are restricted due to the functions of the skin barrier to liposomes. Herein, we proposed a peptide-modified curcumin-loaded liposome (CRC-TD-Lip) to expedite the transdermal delivery of curcumin and enhance the inhibition of psoriasis. CRC-TD-Lip was prepared and dispersed uniformly with high stability and high curcumin encapsulation efficiency. We confirmed the improved intracellular uptake of CRC-TD-Lip, the increased inhibitory effect of CRC-TD-Lip on HaCaT cells, and the heightened transdermal ability of CRC-TD-Lip. Then, the enhanced antipsoriatic ability of CRC-TD-Lip was evaluated in vivo using an imiquimod-induced psoriasis mouse model. The results indicated that the developed CRC-TD-Lip can effectively improve the delivery of curcumin across the skin and enhance the antipsoriasis efficiency. This work can provide a strategy for enhancing the transdermal delivery efficiency of drugs for various skin diseases.


Asunto(s)
Curcumina/administración & dosificación , Curcumina/uso terapéutico , Nanopartículas/química , Péptidos/química , Piel/metabolismo , Administración Cutánea , Animales , Curcumina/química , Liposomas , Ratones , Psoriasis/tratamiento farmacológico
3.
Front Neurol ; 12: 813723, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35115998

RESUMEN

INTRODUCTION: Knee osteoarthritis is a common disease in the elderly. Patients suffer from long-term chronic pain and reduced life quality. Acupuncture has been proven to be an effective treatment for KOA. However, the neural mechanism of acupuncture is unclear, so far. Periaqueductal gray (PAG) and raphe nuclei (RPN) are essential structures associated with chronic pain in human brains. This study aims to investigate functional connectivity (FC) changes of PAG and RPN in KOA to interpret the neural mechanism of acupuncture. METHODS: In 15 patients with KOA and 15 healthy controls (HC), we acquired Visual Analog Scale (VAS) scores and resting-state fMRI images of each participant before and after acupuncture stimulation on EX-LE5 acupoint. Then, PAG and RPN were selected as seeds to perform FC analysis based on resting-state fMRI images. Finally, we compared FC patterns of PAG and RPN between patients with KOA and HC, then between pre-acupuncture and post-acupuncture. Correlations between FC values and VAS scores were calculated as well. RESULTS: For PAG, FC of patients with KOA was lower in the right lingual gyrus at post-acupuncture compared with HC (p <0.001, uncorrected). For dorsal RPN, FC of patients with KOA was significantly higher in right putamen at post-acupuncture compared with HC (p <0.001, corrected with FDR), and FC changes were significant between pre-acupuncture and post-acupuncture in patients with KOA. Post-acupuncture FC values between dorsal RPN and right putamen were correlated with VAS scores. For medial RPN, FC of patients with KOA was lower in the right cerebellum at post-acupuncture compared with HC (p <0.001, uncorrected), but no significant FC changes were found between pre-acupuncture and post-acupuncture in patients with KOA. FC values between medial RPN and right cerebellum were not correlated with VAS scores at pre-acupuncture and post-acupuncture. DISCUSSION: Our study demonstrated that acupuncture enhanced FC between dorsal RPN and the right putamen in patients with KOA, which was associated with chronic pain intensity. This result suggests that acupuncture stimulation can enhance FC between dorsal raphe and striatum, illustrating a neural mechanism that acupuncture can drive the patients' brain, with KOA, to perceive pain.

4.
Front Neurosci ; 15: 737993, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35153654

RESUMEN

Acupuncture is recommended for the relief of chronic tinnitus in traditional Chinese medicine, but the underlying neural mechanism remains unclear. The human brain is a dynamic system, and it's unclear about acupuncture's effects on the dynamic functional connectivity (DFC) of chronic tinnitus. Therefore, this study based on resting-state functional magnetic resonance imaging (fMRI) investigates abnormal DFC in chronic tinnitus patients and the neural activity change evoked by acupuncture treatment for tinnitus. In this study, 17 chronic tinnitus patients and 22 age- and sex-matched normal subjects were recruited, and their tinnitus-related scales and hearing levels were collected. The fMRI data were measured before and after acupuncture, and then sliding-window and k-means clustering methods were used to calculate DFC and perform clustering analysis, respectively. We found that, compared with the normal subjects, chronic tinnitus patients had higher temporal variability of DFC between the supplementary motor area and medial part of the superior frontal gyrus, and it positively correlated with hearing loss. Clustering analysis showed higher transition probability (TP) between connection states in chronic tinnitus patients, and it was positively correlated with tinnitus severity. Furthermore, the findings showed that acupuncture treatment might improve tinnitus. DFC between the posterior cingulate gyrus and angular gyrus in chronic tinnitus patients after acupuncture showed significantly decreased, and it positively correlated with the improvement of tinnitus. Clustering analysis showed that acupuncture treatment might promote chronic tinnitus patients under lower DFC state, and it also positively correlated with the improvement of tinnitus. This study suggests that acupuncture as an alternative therapy method might decrease the tinnitus severity by decreasing the time variability of DFC in chronic tinnitus patients.

5.
ACS Appl Mater Interfaces ; 12(45): 50260-50274, 2020 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-33108154

RESUMEN

Nanozymes that mimic peroxidase (POD) activity can convert H2O2 into bactericidal free radicals, which is referred to as chemodynamic therapy (CDT). High glutathione (GSH) levels in the infectious tissue severely limit the performance of CDT. Herein, we report a near-infrared-controlled antibacterial nanoplatform that is based on encapsulating tungsten sulfide quantum dots (WS2QDs) and the antibiotic vancomycin in a thermal-sensitive liposome. The system exploits the photothermal sensitivity of the WS2QDs to achieve selective liposome rupture for the targeted drug delivery. We determined that WS2QDs show a strong POD-like activity under physiological conditions and the oxidase-like activity, which can oxidate GSH to further improve the CDT efficacy. Moreover, we found that increased temperature promotes multiple enzyme-mimicking activities of WS2QDs. This platform exerts antibacterial effects against Gram-positive Mu50 (a vancomycin-intermediate Staphylococcus aureus reference strain) and Gram-negative Escherichia coli and disrupts biofilms for improved penetration of therapeutic agents inside biofilms. In vivo studies with mice bearing Mu50-caused skin abscess revealed that this platform confers potent antibacterial activity without obvious toxicity. Accordingly, our work illustrates that the photothermal and nanozyme properties of WS2QDs can be deployed alongside a conventional therapeutic to achieve synergistic chemodynamic/photothermal/pharmaco therapy for powerful antibacterial effects.


Asunto(s)
Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Nanopartículas/química , Temperatura , Staphylococcus aureus Resistente a Vancomicina/efectos de los fármacos , Vancomicina/farmacología , Antibacterianos/química , Biopelículas/efectos de los fármacos , Rayos Infrarrojos , Liposomas/química , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Procesos Fotoquímicos , Puntos Cuánticos/química , Sulfuros/química , Propiedades de Superficie , Compuestos de Tungsteno/química , Vancomicina/química
6.
Biomaterials ; 256: 120219, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32736173

RESUMEN

Encouraging progress in multifunctional nanotheranostic agents that combine photothermal therapy (PTT) and different imaging modalities has been made. However, rational designed and biocompatible multifunctional agents that suitfable for in vivo application is highly desired but still challenging. In this work, we rationally designed novel ultrasmall multifunctional nanodots (FS-GdNDs) by combining the bovine serum albumin (BSA)-based gadolinium oxide nanodots (GdNDs) obtained through a biomineralization process with a small-molecule NIR-II fluorophore (FS). The as-prepared FS-GdNDs with an ultrasmall hydrodynamic diameter of 9.3 nm exhibited prominent NIR-II fluorescence properties, high longitudinal relaxivity (10.11 mM-1 s-1), and outstanding photothermal conversion efficiency (43.99%) and photothermal stability. In vivo studies showed that the FS-GdNDs with enhanced multifunctional characteristics diaplayed satisfactory dual-modal MR/NIR-II imaging performance with a quite low dose. The imaging-guided PTT achieved successful ablation of tumors and effectively extended the survival of mice. Cytotoxicity studies and histological assay demonstrated excellent biocompatibility of the nanodots. Importantly, this novel FS-GdNDs can undergo efficient body clearance through both hepatobiliary and renal excretion pathways. The novel ultrasmall multifunctional FS-GdNDs with excellent features hold tremendous potential in biomedical and clinical applications.


Asunto(s)
Neoplasias , Fototerapia , Animales , Imagen por Resonancia Magnética , Ratones , Nanoestructuras , Neoplasias/terapia , Terapia Fototérmica , Albúmina Sérica Bovina
7.
Artículo en Inglés | MEDLINE | ID: mdl-32148548

RESUMEN

BACKGROUND: Clinical and experimental data suggest that ultrasound stimulation (US) at acupoints can produce similar effective treatment compared to manual acupuncture (MA). Although the brain activation to MA at acupoints is investigated by numerous studies, the brain activation to US at acupoints remains unclear. METHODS: In the present work, we employed task state functional magnetic resonance imaging (fMRI) to explore the human brain's activation to US and MA at ST 36 (Zusanli) which is one of the most commonly used acupoints in acupuncture-related studies. 16 healthy subjects underwent US and MA procedures in an interval of more than one week. On-off block design stimulation was used for the recording of fMRI-related brain patterns. RESULTS: Both US and MA at ST 36 produced activations in somatosensory and limbic/paralimbic regions (postcentral gyrus, insula, middle prefrontal cortex, and anterior cingulate cortex). Only US at ST 36 produced a significant signal increase in the inferior parietal lobule and decrease in the posterior cingulate cortex, whereas MA at ST 36 produced a significant signal increase in the lentiform nucleus and cerebellum. CONCLUSIONS: Our results indicate that US may be a possible noninvasive alternative method to MA due to its similar activation patterns.

8.
Adv Healthc Mater ; 7(19): e1800322, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30303632

RESUMEN

Multifunctional theranostic nanoagents which realize precise diagnosis and treatment of tumors are attracting increasing interests in recent years. However, efficient and controlled synthesis of ultra-small noble metal nanoagents remains a challenge. Here, monodisperse Gd/Ru@BSA nanodots (GRBNDs) are successfully fabricated via a totally "green", "one-pot" protocol for in situ reduction of Ru(III) and biomineralization of Gd(III) in the presence of albumin. The as-prepared nanoagent possesses the features of being ultra small in size (≈6.7 nm), having strong colloidal stability, and thermal stability as well as high photothermal conversion efficiency (η = 50.7%). As expected, the GRBNDs achieve a significant efficacy of anticancer therapy under LASER activation both in vitro and in vivo. It also exhibits superior T1 -weighted magnetic resonance (MR) imaging ability due to its high longitudinal relaxivity value (r1 = 10.98 × 10-3 m-1 s-1 ). Moreover, it is demonstrated to be renal clearable with negligible systemic toxicity. This work highlights a straightforward and repeatable approach for synthesizing highly effective and multifunctional noble metal nanoagent of great clinical promising for cancer theranostics.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Imagen Multimodal/métodos , Fototerapia/métodos , Albúmina Sérica Bovina/química , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/terapia , Línea Celular Tumoral , Femenino , Ratones , Microscopía Electrónica de Transmisión
9.
Comput Methods Programs Biomed ; 143: 67-74, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28391820

RESUMEN

BACKGROUND AND OBJECTIVE: Automatic osteosarcoma tumor segmentation on computed tomography (CT) images is a challenging problem, as tumors have large spatial and structural variabilities. In this study, an automatic tumor segmentation method, which was based on a fully convolutional networks with multiple supervised side output layers (MSFCN), was presented. METHODS: Image normalization is applied as a pre-processing step for decreasing the differences among images. In the frame of the fully convolutional networks, supervised side output layers were added to three layers in order to guide the multi-scale feature learning as a contracting structure, which was then able to capture both the local and global image features. Multiple feature channels were used in the up-sampling portion to capture more context information, for the assurance of accurate segmentation of the tumor, with low contrast around the soft tissue. The results of all the side outputs were fused to determine the final boundaries of the tumors. RESULTS: A quantitative comparison of the 405 osteosarcoma manual segmentation results from the CT images showed that the average Dice similarity coefficient (DSC), average sensitivity, average Hammoude distance (HM) and F1-measure were 87.80%, 86.88%, 19.81% and 0.908, respectively. It was determined that, when compared with the other learning-based algorithms (for example, the fully convolution networks (FCN), U-Net method, and holistically-nested edge detection (HED) method), the MSFCN had the best performances in terms of DSC, sensitivity, HM and F1-measure. CONCLUSION: The results indicated that the proposed algorithm contributed to the fast and accurate delineation of tumor boundaries, which could potentially assist doctors in making more precise treatment plans.


Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Osteosarcoma/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Algoritmos , Niño , Medios de Contraste , Humanos , Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tomógrafos Computarizados por Rayos X , Adulto Joven
10.
Artículo en Inglés | MEDLINE | ID: mdl-27293461

RESUMEN

Bell's palsy (BP), an acute unilateral facial paralysis, is frequently treated with acupuncture in many countries. However, the mechanism of treatment is not clear so far. In order to explore the potential mechanism, 22 healthy volunteers and 17 BP patients with different clinical duration were recruited. The resting-state functional magnetic resonance imaging scans were conducted before and after acupuncture at LI4 (Hegu), respectively. By comparing BP-induced functional connectivity (FC) changes with acupuncture-induced FC changes in the patients, the abnormal increased FC that could be reduced by acupuncture was selected. The FC strength of the selected FC at various stages was analyzed subsequently. Our results show that FC modulation of acupuncture is specific and consistent with the tendency of recovery. Therefore, we propose that FC modulation by acupuncture may be beneficial to recovery from the disease.

11.
Nanoscale ; 8(25): 12826-33, 2016 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-27297334

RESUMEN

T1-T2 dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T1-T2 dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T1-T2 dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual-modal CAs and their application for enhanced T1-T2 MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe3O4/Gd2O3 nanocubes have an r1 value of 45.24 mM(-1) s(-1) and an r2 value of 186.51 mM(-1) s(-1), which were about two folds of those of Gd2O3 nanoparticles and Fe3O4 nanocubes, respectively. In vivo MR imaging of rats showed both T1-positive and T2-negative contrast enhancements in the livers. We envision that our Fe3O4/Gd2O3 nanocubes could be applied as T1-T2 dual modal MR CAs for a wide range of theranostic applications in the near future.

12.
Neuroreport ; 26(1): 6-12, 2015 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-25426823

RESUMEN

Bell's palsy (BP), a unilateral and idiopathic palsy of the facial nerve, is a common disorder generally followed by a good natural recovery. The aim of this study was to investigate the relationship between the functional connectivity of the anterior cingulate cortex (ACC) and the recovery process of BP. Thirty-seven healthy volunteers and 67 patients were studied by functional MRI (fMRI). The seed regions of bilateral ACC were first extracted from the task-state fMRI data of healthy participants performing the task of mouth opening and closing. The connectivity of bilateral ACC was calculated from resting-state fMRI data of patients in whom only resting-state fMRI data were collected. The correlation between the strength of ACC's connectivity with the duration (time course of disease) was computed by analysis of covariance. It was found that the functional connectivity of the ACC ipsilateral to the lesioned side was enforced as the duration increased. The enforced brain areas included the sensorimotor areas and the ACC contralateral to the palsy. It was suggested that enforced functional connectivity of ACC might be related to cortical reorganization, which is important in the process of BP recovery.


Asunto(s)
Parálisis de Bell/fisiopatología , Giro del Cíngulo/fisiopatología , Recuperación de la Función/fisiología , Terapia por Acupuntura , Adulto , Parálisis de Bell/terapia , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Actividad Motora/fisiología , Boca/fisiopatología , Vías Nerviosas/fisiopatología , Descanso , Factores de Tiempo
13.
Neuroreport ; 25(14): 1162-8, 2014 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-25121624

RESUMEN

Bell's palsy is the most common cause of acute facial nerve paralysis. In China, Bell's palsy is frequently treated with acupuncture. However, its efficacy and underlying mechanism are still controversial. In this study, we used functional MRI to investigate the effect of acupuncture on the functional connectivity of the brain in Bell's palsy patients and healthy individuals. The patients were further grouped according to disease duration and facial motor performance. The results of resting-state functional MRI connectivity show that acupuncture induces significant connectivity changes in the primary somatosensory region of both early and late recovery groups, but no significant changes in either the healthy control group or the recovered group. In the recovery group, the changes also varied with regions and disease duration. Therefore, we propose that the effect of acupuncture stimulation may depend on the functional connectivity status of patients with Bell's palsy.


Asunto(s)
Terapia por Acupuntura , Parálisis de Bell/fisiopatología , Corteza Somatosensorial/fisiopatología , Adulto , Anciano , Cara/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Actividad Motora/fisiología , Vías Nerviosas/fisiopatología , Factores de Tiempo , Adulto Joven
14.
PLoS One ; 9(5): e97502, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24821143

RESUMEN

Most previous studies of brain responses to acupuncture were designed to investigate the acupuncture instant effect while the cumulative effect that should be more important in clinical practice has seldom been discussed. In this study, the neural basis of the acupuncture cumulative effect was analyzed. For this experiment, forty healthy volunteers were recruited, in which more than 40 minutes of repeated acupuncture stimulation was implemented at acupoint Zhusanli (ST36). Three runs of acupuncture fMRI datasets were acquired, with each run consisting of two blocks of acupuncture stimulation. Besides general linear model (GLM) analysis, the cumulative effects of acupuncture were analyzed with analysis of covariance (ANCOVA) to find the association between the brain response and the cumulative duration of acupuncture stimulation in each stimulation block. The experimental results showed that the brain response in the initial stage was the strongest although the brain response to acupuncture was time-variant. In particular, the brain areas that were activated in the first block and the brain areas that demonstrated cumulative effects in the course of repeated acupuncture stimulation overlapped in the pain-related areas, including the bilateral middle cingulate cortex, the bilateral paracentral lobule, the SII, and the right thalamus. Furthermore, the cumulative effects demonstrated bimodal characteristics, i.e. the brain response was positive at the beginning, and became negative at the end. It was suggested that the cumulative effect of repeated acupuncture stimulation was consistent with the characteristic of habituation effects. This finding may explain the neurophysiologic mechanism underlying acupuncture analgesia.


Asunto(s)
Terapia por Acupuntura/métodos , Encéfalo/fisiopatología , Habituación Psicofisiológica , Imagen por Resonancia Magnética , Manejo del Dolor/métodos , Dolor/psicología , Adulto , Femenino , Humanos , Masculino , Factores de Tiempo , Adulto Joven
15.
Acupunct Med ; 31(4): 404-8, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23956382

RESUMEN

OBJECTIVE: To evaluate the MR compatibility of three metal acupuncture needles (a standard stainless steel needle, a gold needle and an austenitic stainless steel needle) by comparing their imaging artefacts, radiofrequency heating effects and ease of operation. METHODS: The MRI artefacts of the three metal needles were first evaluated by placing them in an agar gel phantom and performing MRI of the phantom. The increase in temperature during MRI was recorded using an MR-compatible fibreoptic thermometer. MRI of acupuncture at SP6 was performed using the MR-compatible gold needle and the austenitic stainless steel needle. RESULTS: The standard stainless steel acupuncture needle produced large imaging artefacts on MRI. The gold needle was superior for MRI but not rigid enough for some clinical applications such as scalp acupuncture. The austenitic stainless steel needle is non-ferromagnetic and compatible with MRI. None of these acupuncture needles introduced radiofrequency heating during MRI. CONCLUSIONS: The evaluation of MR compatibility showed that gold and austenitic stainless steel needles are MR-compatible and therefore can be used for MRI of acupuncture.


Asunto(s)
Terapia por Acupuntura/instrumentación , Agujas/normas , Puntos de Acupuntura , Humanos , Imagen por Resonancia Magnética , Control de Calidad
16.
Acad Radiol ; 13(4): 526-30, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16554234

RESUMEN

RATIONALE AND OBJECTIVES: We evaluated the potential of using intravascular magnetic resonance (MR)/radiofrequency (RF) to enhance vascular endothelial growth factor (VEGF) gene therapy of in-stent neointimal hyperplasia. MATERIALS AND METHODS: By using a catheter-based approach, VEGF/lentivirus was locally transferred into 10 (five paired) bilateral femoral-iliac arteries of five hypercholesterolemic pigs, whereas the right arteries were heated up to approximately 41 degrees C by using an intravascular MR/RF system. Then, identical stents were placed immediately into the bilateral VEGF-targeted arteries to create in-stent neointimal hyperplasia. At day 60 after gene/stent interventions, the targeted arteries were harvested for histological correlation. RESULTS: X-Ray angiography-detectable in-stent stenoses were found in three of the arteries treated with VEGF genes only, whereas there were no in-stent stenoses in arteries treated by using MR/RF-heated VEGF genes. Correlative histological examination confirmed a 138% reduction in average thickness of neointimal hyperplasia in VEGF/RF-treated arteries compared with VEGF-only-treated arteries (P < .01). CONCLUSION: We report a potential method of using an intravascular MR/RF heating technique to enhance gene therapy of in-stent restenosis.


Asunto(s)
Terapia Genética/métodos , Oclusión de Injerto Vascular/prevención & control , Magnetismo/uso terapéutico , Terapia por Radiofrecuencia , Stents/efectos adversos , Transfección/métodos , Factor A de Crecimiento Endotelial Vascular/administración & dosificación , Animales , Oclusión de Injerto Vascular/etiología , Porcinos , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/genética
17.
Radiology ; 236(3): 939-44, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16040894

RESUMEN

PURPOSE: To evaluate the feasibility of radiofrequency (RF)-enhanced vascular gene transduction and expression by using a magnetic resonance (MR) imaging-heating guidewire as an intravascular heating vehicle during MR imaging-guided therapy. MATERIALS AND METHODS: The institutional committee for animal care and use approved the experimental protocol. The study included in vitro evaluation of the use of RF energy to enhance gene transduction and expression in vascular cells, as well as in vivo validation of the feasibility of intravascular MR imaging-guided RF-enhanced vascular gene transduction and expression in pig arteries. For in vitro experiments, approximately 10(4) vascular smooth muscle cells were seeded in each of four chambers of a cell culture plate. Next, 1 mL of a green fluorescent protein gene (gfp)-bearing lentivirus was added to each chamber. Chamber 4 was heated at approximately 41 degrees C for 15 minutes by using an MR imaging-heating guidewire connected to a custom RF generator. At day 6 after transduction, the four chambers were examined and compared at confocal microscopy to determine the efficiency of gfp transduction and expression. For the in vivo experiments, a lentivirus vector bearing a therapeutic gene, vascular endothelial growth factor 165 (VEGF-165), was transferred by using a gene delivery balloon catheter in 18 femoral-iliac arteries (nine artery pairs) in domestic pigs and Yucatan pigs with atherosclerosis. During gene infusion, one femoral-iliac artery in each pig was heated to approximately 41 degrees C with RF energy transferred via the intravascular MR imaging-heating guidewire, while the contralateral artery was not heated (control condition). At day 6, the 18 arteries were harvested for quantitative Western blot analysis to compare VEGF-165 transduction and expression efficiency between RF-heated and nonheated arterial groups. RESULTS: Confocal microscopy showed gfp expression in chamber 4 that was 293% the level of expression in chamber 1 (49.6% +/- 25.8 vs 16.8% +/- 8.0). Results of Western blot analysis showed VEGF-165 expression for normal arteries in the RF-heated group that was 300% the level of expression in the nonheated group (70.4 arbitrary units [au] +/- 107.1 vs 23.5 au +/- 29.8), and, for atherosclerotic arteries in the RF-heated group, 986% the level in the nonheated group (129.2 au +/- 100.3 vs 13.1 au +/- 4.9). CONCLUSION: Simultaneous monitoring and enhancement of vascular gene delivery and expression is feasible with the MR imaging-heating guidewire.


Asunto(s)
Cateterismo/métodos , Terapia Genética , Hipertermia Inducida/métodos , Imagen por Resonancia Magnética , Terapia por Radiofrecuencia , Enfermedades Vasculares/terapia , Animales , Western Blotting , Estudios de Factibilidad , Vectores Genéticos , Proteínas Fluorescentes Verdes , Lentivirus/genética , Músculo Liso Vascular/citología , Porcinos
18.
Magn Reson Med ; 54(1): 226-30, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15968681

RESUMEN

Previous studies have confirmed the possibility of using an intravascular MR imaging guidewire (MRIG) as a heating source to enhance vascular gene transfection/expression. This motivated us to develop a new intravascular system that can perform MR imaging, radiofrequncy (RF) heating, and MR temperature monitoring simultaneously in an MR scanner. To validate this concept, a series of mathematical simulations of RF power loss along a 0.032-inch MRIG and RF energy spatial distribution were performed to determine the optimum RF heating frequency. Then, an RF generator/amplifier and a filter box were built. The possibility for simultaneous RF heating and MR thermal mapping of the system was confirmed in vitro using a phantom, and the obtained thermal mapping profile was compared with the simulated RF power distribution. Subsequently, the feasibility of simultaneous RF heating and temperature monitoring was successfully validated in vivo in the aorta of living rabbits. This MR imaging/RF heating system offers a potential tool for intravascular MR-mediated, RF-enhanced vascular gene therapy.


Asunto(s)
Aorta Abdominal/anatomía & histología , Aorta Abdominal/fisiología , Cateterismo/métodos , Hipertermia Inducida/métodos , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Terapia por Radiofrecuencia , Termografía/métodos , Animales , Conejos , Integración de Sistemas
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