RESUMO
Surgery remains one of the main treatments of cancer and both precise pre- and intraoperative diagnoses are crucial in order to guide the operation. We consider that using an identical probe for both pre- and intra-operative diagnoses would bridge the gap between surgical planning and image-guided resection. Therefore, in this study, we developed gold nanorods (AuNRs) conjugated with radiolabeled anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, and investigated their feasibility as novel HER2-targeted dual-imaging probes for both single photon emission computed tomography (SPECT) (preoperative diagnosis) and photoacoustic (PA) imaging (intraoperative diagnosis). To achieve the purpose, AuNRs conjugated with different amount of trastuzumab (Tra) were prepared, and Tra-AuNRs were labeled with indium-111. After the evaluation of binding affinity to HER2, cell binding assay and biodistribution studies were carried out for optimization. AuNRs with moderate trastuzumab conjugation (Tra2-AuNRs) were proposed as the novel probe and demonstrated significantly higher accumulation in NCI-N87 (HER2 high-expression) tumors than in SUIT2 (low-expression) tumors 96 h post-injection along with good affinity towards HER2. Thereafter, in vitro PA imaging and in vivo SPECT imaging studies were performed. In in vitro PA imaging, Tra2-AuNRs-treated N87 cells exhibited significant PA signal increase than SUIT2 cells. In in vivo SPECT, signal increase in N87 tumors was more notable than that in SUIT2 tumors. Herein, we report that the Tra2-AuNRs enabled HER2-specific imaging, suggesting the potential as a robust HER2-targeted SPECT and PA dual-imaging probe.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Desenvolvimento de Medicamentos/métodos , Nanotubos , Neoplasias/metabolismo , Técnicas Fotoacústicas/métodos , Receptor ErbB-2/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/metabolismo , Linhagem Celular Tumoral , Feminino , Ouro/administração & dosagem , Ouro/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/diagnóstico por imagem , Neoplasias/genética , Ligação Proteica/fisiologia , Receptor ErbB-2/genéticaRESUMO
PURPOSE: This study aimed to elucidate the relationship between diurnal masseter muscle activity and awareness of diurnal awake bruxism (d-AB) by conducting a comparative analysis of electromyographic (EMG) data from individuals with and without awareness of diurnal awake bruxism (d-AB), utilizing EMG data gathered from multiple subjects. METHODS: Unilateral masseter electromyography (EMG) recordings were performed during the daytime using an ultraminiature wearable EMG device. A total of 119 participants (59 with awareness of diurnal tooth clenching [d-TC] and 60 without awareness of d-TC) were included. Waveforms longer than 0.25 s with the two amplitude conditions, exceeding twice the baseline and >5% of maximum voluntary clenching, were extracted. In addition, the number of bursts and episodes (groups of bursts), burst duration, and burst peak amplitude were calculated for each participant. RESULTS: There were no significant differences in the EMG parameters between the groups with and without awareness of d-TC. Additionally, the frequency distribution of the number of EMG waveforms exhibited wide ranges and substantial overlap between the two groups. CONCLUSIONS: The variability in the number of bursts and episodes, burst peak amplitude, and burst duration among subjects suggests the need for an objective classification of d-AB severity based on EMG values. The absence of significant differences and large overlap in frequency distributions between the groups with and without awareness of d-TC indicate difficulty in predicting muscle activity solely based on awareness of d-AB.
Assuntos
Conscientização , Bruxismo , Eletromiografia , Músculo Masseter , Vigília , Humanos , Músculo Masseter/fisiopatologia , Músculo Masseter/fisiologia , Bruxismo/fisiopatologia , Masculino , Feminino , Adulto , Vigília/fisiologia , Conscientização/fisiologia , Ritmo Circadiano/fisiologia , Adulto Jovem , Pessoa de Meia-IdadeRESUMO
Skin aging caused by ultraviolet light exposure is one of the serious problems from the viewpoint of beauty and healthcare. This is because ultraviolet light can cause age spot, wrinkles, at the worst case, skin cancer and so on. To evaluate skin aging, various modalities are being used, such as histopathological diagnosis, optical coherence tomography, ultrasound examination (B-mode imaging). However, they have disadvantages in terms of invasiveness, penetration depth and tissue specificity, respectively. To overcome these defects, photoacoustic imaging (PAI), a novel modality was used in this work. This modality can sense differences of tissue characteristics non-invasively. In this experiment, human skin tissues in various generations (i.e. various degrees of photoaging) were measured by using acoustic resolution photoacoustic microscopy (AR-PAM). To verify the feasibility of quantitative skin aging evaluation with PA technique, signals from sectioned human skin (cheek and buttock; female from 28 to 95 years old) were measured with PA microscopy. The effects of photoaging progress on the signal intensity were investigated. The results demonstrated that the PA signal from the dermis significantly increases with aging progress (p < 0.05). These analyses demonstrate the feasibility of quantitative skin aging evaluation with a PAI system.
Assuntos
Técnicas Fotoacústicas , Envelhecimento da Pele , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Microscopia Acústica , Pessoa de Meia-Idade , Tomografia de Coerência Óptica , UltrassonografiaRESUMO
In order to completely remove tumors in surgeries, probes are needed both preoperatively and intraoperatively. For tumor diagnosis, magnetic resonance imaging (MRI) has been widely used as a precise preoperative method, and photoacoustic imaging (PAI) is a recently emerged intraoperative (or preoperative) method, which detects ultrasonic waves thermoelastically induced by optical absorbers irradiated by laser. Iron oxide nanoparticles (IONPs) can be used as both MR and PA imaging probes. In order to improve the sensitivity of IONPs as MR/PA imaging probes, we newly prepared liposomes encapsulated with a number of IONPs (Lipo-IONPs). Interestingly, Lipo-IONPs showed 2.6 and 3.8-times higher PA and MR signals, respectively, compared to dispersed IONPs at the same concentration. Furthermore, trastuzumab (Tra) (anti-human epidermal growth factor receptor 2 (EGFR2; HER2) monoclonal antibody) was introduced onto the surface of liposomes for detection of HER2 related to tumor malignancy. In an cellular uptake study, Tra-Lipo-IONPs were taken up by HER2-positive tumor cells and HER2-specific MR/PA dual imaging was achieved. Finally, a biodistribution study using radiolabeled Tra-Lipo-IONPs showed HER2-specific tumor accumulation. In conclusion, we demonstrated the usefulness of Lipo-IONPs as platforms for sensitive MR/PA dual imaging and the possibility of HER2-specific tumor MR/PA imaging using Tra-Lipo-IONPs.
Assuntos
Imageamento por Ressonância Magnética , Linhagem Celular Tumoral , Espectroscopia de Ressonância Magnética , Distribuição Tecidual , TrastuzumabRESUMO
Backscattered light was used to reconstruct cross-sectional images of absorption distributions in diffuse media. For efficient and accurate reconstruction, the inverse problem was solved for one dimension, thereby yielding the absorption distribution in a depth direction. A cross-sectional image or three-dimensional structure is reconstructed by shifting a source-detector pair along the object surface. The object is divided into imaginary layers to solve the inverse problem. This solution's accuracy is further improved by solving the problem for two groups of layers successively instead of solving for all layers simultaneously. The technique's effectiveness was verified using solid phantoms and biological tissues.
Assuntos
Luz , Espalhamento de Radiação , Tomografia Óptica , Abdome , Absorção , Animais , Galinhas , Estudos de Viabilidade , Rim/efeitos da radiação , Camundongos , Modelos Biológicos , Imagens de Fantasmas , Suínos , Fatores de TempoRESUMO
For early diagnosis of rheumatoid arthritis (RA), it is important to visualize its potential marker, vascularization in the synovial membrane of the finger joints. Photoacoustic (PA) imaging, which can image blood vessels at high contrast and resolution, is expected to be a potential modality for earlier diagnosis of RA. In previous studies of PA finger imaging, different acoustic schemes, such as linear-shaped arrays, have been utilized, but these have limited detection views, rendering inaccurate reconstruction, and most of them require rotational detection. We are developing a PA system for finger vascular imaging using a ring-shaped array ultrasound (US) transducer. By designing the ring-array sensor based on simulations, using phantom experiments, it was demonstrated that we have created a system that can image small objects around 0.1 to 0.5 mm in diameter. The full width at half maximum of the slice direction of the system was within 2 mm and corresponded to that of the simulation. Moreover, we could clearly visualize healthy index finger vasculature and the location of the distal interphalangeal and proximal interphalangeal joints by PA and US echo images. In the future, this system could be used as a method for visualizing the three-dimensional vascularization of RA patients' fingers.
Assuntos
Artrite Reumatoide/diagnóstico por imagem , Dedos , Interpretação de Imagem Assistida por Computador/métodos , Técnicas Fotoacústicas/métodos , Desenho de Equipamento , Dedos/irrigação sanguínea , Dedos/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Imagens de Fantasmas , Técnicas Fotoacústicas/instrumentação , TransdutoresRESUMO
To realize three-dimensional (3D) optical imaging of the internal structure of an animal body, we have developed a new technique to reconstruct optical computed tomography (optical CT) images from two-dimensional (2D) transillumination images. In transillumination imaging of an animal body using near-infrared light, the image is blurred because of the strong scattering in the tissue. To overcome this problem, we propose a novel technique to apply the point spread function (PSF) for a light source located inside the medium to the transilluminated image of light-absorbing structure. The problem of the depth-dependence of PSF was solved in the calculation of the projection image in the filtered back-projection method. The effectiveness of the proposed technique was assessed in the experiments with a model phantom and a mouse. These analyses verified the feasibility of the practical 3D imaging of the internal light-absorbing structure of a small animal.
RESUMO
To find an early symptom of postprandial hyperlipidemia, we developed a technique to measure the change in triglyceride noninvasively. We examined the feasibility to measure the change in the triglyceride concentration as the change in the scattering coefficient of the blood. In an experiment, good correlation was obtained between the change in the triglyceride after a meal and the optical change. This suggested the feasibility of the noninvasive measurement of the triglyceride in blood.
Assuntos
Hiperlipidemias/sangue , Hiperlipidemias/diagnóstico , Pele/patologia , Triglicerídeos/sangue , Adulto , Desenho de Equipamento , Jejum , Humanos , Luz , Masculino , Óptica e Fotônica , Período Pós-Prandial , Reprodutibilidade dos Testes , Espalhamento de RadiaçãoRESUMO
In transillumination imaging of an animal body with near-infrared light, the shallower structure appears clearer. Therefore, we can reconstruct the three dimensional (3D) image of the shallow structure using the transillumination images as the projection images. In the 3D reconstruction, it may be better to use the projection images of limited observation-angle range rather than those from 360° range. We investigated this possibility and devised a new technique to reconstruct the 3D image of the light absorbing structure in shallow region of a turbid medium. This technique is applicable to the turbid object without any a priori knowledge on the angular position of the absorbing structure. The feasibility of the proposed technique was verified in experiments.
Assuntos
Imageamento Tridimensional/métodos , Animais , Humanos , Imagens de Fantasmas , Transiluminação/métodosRESUMO
In transillumination imaging of an animal body using near-infrared light, the image is blurred due to the strong scattering in the tissue. We have devised the depth-dependent point spread function (PSF) to suppress the scattering effect in fluorescent imaging. In this study, we applied this principle and developed a technique to reconstruct the absorbing structure in turbid medium without using fluorescent material. In experiments, the feasibility and effectiveness of the proposed technique were verified.
Assuntos
Imageamento Tridimensional/métodos , Transiluminação/métodos , Algoritmos , Animais , Fluorescência , Imagens de FantasmasRESUMO
The depth of fluorescent source is required to suppress the scattering effect in transcutaneous fluorescent imaging. We have developed a technique to estimate the depth using two light sources. However, with this technique, the reduced scattering coefficient (µs') and the absorption coefficient (µa) of the scattering medium have to be known a priori. To eliminate this requirement, we devised a technique that uses three excitation sources. The feasibility of the proposed technique was verified in both computer simulation and experiment. It was demonstrated that we could estimate the depth of the fluorescent source and improve the fluorescent image even with µs' and µa variation.
Assuntos
Aumento da Imagem , Fenômenos Ópticos , Espalhamento de Radiação , Absorção de Radiação , Calibragem , Simulação por Computador , Fluorescência , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The size of lipoprotein particles is relevant to the risk of coronary artery disease (CAD). METHODS: We investigated the feasibility of atomic force microscopy (AFM) for evaluating the size of large low-density lipoprotein (LDL) and small dense LDL (sd-LDL) separated by ultracentrifugation. The measurements by AFM in tapping mode were compared to those by electron microscopy (EM). RESULTS: There was a significant difference in particle sizes determined by AFM between large LDL (20.6 ± 1.9 nm, mean ± SD) and sd-LDL (16.2 ± 1.4 nm) obtained from six healthy volunteers (P < 0.05). The particle sizes determined by EM for the same samples were 23.2 ± 1.4 nm for large LDL and 20.4 ± 1.4 nm for sd-LDL. The difference between large LDL and sd-LDL detected by EM was also statistically significant (P < 0.05). In addition, the particle sizes of each lipoprotein fraction were significantly different between AFM and EM: P < 0.05 for large LDL and P < 0.05 for sd-LDL. CONCLUSIONS: AFM can differentiate between sd-LDL and large LDL particles by their size, and might be useful for evaluating risk for CAD.
Assuntos
Análise Química do Sangue/métodos , Lipoproteínas LDL/sangue , Microscopia de Força Atômica/métodos , Adulto , Estudos de Viabilidade , Humanos , Lipoproteínas LDL/química , Masculino , Tamanho da Partícula , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND: A simple method for the measurement of LDL particle sizes is needed in clinical laboratories because a predominance of small, dense LDL (sd LDL) has been associated with coronary heart disease. We applied dynamic light scattering (DLS) to measure lipoprotein particle sizes, with special reference to sd LDL. METHODS: Human serum lipoproteins isolated by a combination of ultracentrifugation and gel chromatography, or by sequential ultracentrifugation, were measured for particle size using DLS. RESULTS: The sizes of polystyrene beads, with diameters of 21 and 28 nm according to the manufacturer, were determined by DLS as 19.3 +/- 1.0 nm (mean +/- SD, n = 11) and 25.5 +/- 1.0 nm, respectively. The coefficients of variation for the 21 and 28 nm beads were 5.1% and 3.8% (within-run, n = 11), and 2.9% and 6.2% (between-run, n = 3), respectively. The lipoprotein sizes determined by DLS for lipoprotein fractions isolated by chromatography were consistent with the elution profile. Whole serum, four isolated lipoprotein fractions (CM + VLDL + IDL, large LDL, sd LDL and HDL) and a non-lipoprotein fraction isolated by sequential ultracentrifugation were determined by DLS to be 13.1 +/- 7.5, 37.0 +/- 5.2, 21.5 +/- 0.8, 20.3 +/- 1.1, 8.6 +/- 1.5 and 8.8 +/- 2.0 nm, respectively. CONCLUSIONS: The proposed DLS method can differentiate the sizes of isolated lipoprotein particles, including large LDL and sd LDL, and might be used in clinical laboratories in combination with convenient lipoprotein separation.