Multispectral photoacoustic imaging of tumours in mice injected with an enzyme-activatable photoacoustic probe
Multispectral photoacoustic imaging of tumours in mice injected with an enzyme-activatable photoacoustic probe
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DOI：
10.1088/2040-8978/19/1/014002
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发表时间：
2017-01-01
影响因子：
2.1
通讯作者：
Ishihara, Miya
中科院分区：
文献类型：
--
作者：
Hirasawa, Takeshi;Iwatate, Ryu J.;Ishihara, Miya
光声（PA）成像提供了具有超声成像空间分辨率的光学吸收体的深度分辨图像。为了增强肿瘤对比度，肿瘤特异性探针被用作造影剂。我们合成了一种无色的PA探针，它在γ-谷氨酰转肽酶（一种癌症相关酶）的存在下被激活，以显示其原始颜色和荧光。我们已经获得了小肿瘤的高特异性荧光图像，使用基于类似酶反应的荧光探针。在这里，我们开发了一种PA成像技术来检测PA探头。在PA成像中，根据探针的浓度和激发波长，探针信号的强度可能低于由固有光吸收体（例如血红蛋白）产生的背景信号的强度。对于在强背景信号存在下的探针成像，评估了多光谱光声（MS-PA）成像。在MS-PA成像中，利用参考谱区分探测信号和背景信号的谱拟合方法得到了广泛的应用。为了补偿由于生物组织中的光学衰减而导致的注量降低，我们使用了一种简化的补偿方法，该方法使用关于生物组织的光学特性的公开数据通过蒙特-卡罗模型计算生物组织内部的注量。该方法的有效性得到了仿组织体模的验证。最后，MS-PA成像的小鼠皮下肿瘤注射的可激活的探针进行了演示。总之，我们的MS-PA成像技术提供了成功的检测激活的探针在肿瘤中，并成功地观察到PA信号的时间增加。
Photoacoustic (PA) imaging offers depth-resolved images of optical absorbers with the spatial resolution of ultrasound imaging. To enhance tumour contrast, tumour-specific probes are used as contrast agents. We synthesised a colourless PA probe that is activated in the presence of gamma-glutamyltranspeptidase, a cancer-associated enzyme, to show its original colour and fluorescence. We have acquired high specificity fluorescence images of small tumours, using a fluorescent probe based on similar enzymatic reactions. Here, we developed a PA imaging technique to detect the PA probe. In PA imaging, depending on the concentration and excitation wavelength of the probe, the intensities of the probe signals may be lower than those of the background signals produced by intrinsic optical absorbers such as haemoglobin. For probe imaging in the presence of strong background signals, multispectral photoacoustic (MS-PA) imaging was evaluated. In MS-PA imaging, the spectral fitting method, which distinguishes the probe signals from background signals using reference spectra, has been widely used. To compensate for the decrease of fluence due to optical attenuation in biological tissue, we used a simplified compensation method that calculates fluence inside biological tissues by the Monte-Carlo model using published data on optical properties of biological tissues. The validity of the method was confirmed using tissue-mimicking phantoms. Finally, MS-PA imaging of a mouse subcutaneous tumour injected with the activatable probe was demonstrated. In conclusion, our MS-PA imaging technique afforded successful detection of the activated probe in the tumour, and time-increase of PA signals were successfully observed.