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根据光声效应,光声成像的原理如图 1所示。当使用短脉冲激光照射生物组织时,入射激光的能量会被组织中的吸收子(如血细胞、血红蛋白、黑色素等)吸收并转换为热能,从而导致组织产生瞬时热弹性膨胀并挤压周围组织从而产生超声信号,用超声换能器接收该光声信号,经扫描后最终成像。
光声信号强度与入射光脉冲强度和观测对象的光吸收系数成正比:
$ {P_0}\left( z \right) = \mathit{\Gamma }{\mu _{\rm{a}}}{F_0}{\rm{exp}}( - {\mu _0}z) $
(1) 式中, P0(z)为光声信号的强度,μa是光吸收系数,F0是入射光波强度,μ0为超声衰减系数,z为传播距离,Γ为比例常数。
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根据光声成像的原理,对其激励光源的要求主要为热限制τth和压力限制τs[28-29]:
$ \left\{ \begin{array}{l} {\tau _{{\rm{th}}}} \approx {L_{\rm{p}}}^2/(4{D_{\rm{t}}})\\ {\tau _{\rm{s}}} = {L_{\rm{p}}}/c \end{array} \right. $
(2) 式中,Lp是组织吸收结构的尺寸,Dt是热扩散系数,c是超声波在组织中的传播速度。通常软组织的Dt=1.4×10-3cm2/s,c=1540m/s,设Lp=150μm,则根据公式可得:τth=40.2ms,τs=97.4ns。可见,热限制τth要求光声光源脉宽必须小于40.2ms,一般脉冲光源都能符合;而压力限制τs则要求光源脉宽小于97.4ns,这就决定了光声激励光源的脉宽要小于97.4ns。如此,光源的脉冲持续时间就会比组织吸收体的热扩散和压力扩散的时间还要小,进而在光声成像中热扩散和压力扩散的影响便可忽略[30]。因此,目前光声成像中应用的多为脉宽小于100ns的短脉冲激光器。
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由(1)式可知,为了获得更高的光声信号,激光的入射功率或光强应越大越好。但考虑其对探测目标尤其是生物组织的伤害,因此对于光声激励光源功率或光强的要求主要是基于安全考虑。以美国国家标准(American National Standard Z136.1-2000)定义的生物组织最大辐射剂量(maximum permissible exposure,MPE)为例,在光声常用的可见光和近红外区域(400nm~1400nm),对皮肤组织来说,光声所使用短脉冲激光(1ns~100ns)的MPE(单位:mJ/cm2)为[31]:
$ \left\{ \begin{array}{l} 20, (400{\rm{nm}} < \mathit{\lambda } < 700{\rm{nm}})\\ 20 \times {10^{2(\lambda - 0.7)}}, (700{\rm{nm}} < \mathit{\lambda } < 1050{\rm{nm}})\\ 100, (1050{\rm{nm}} < \mathit{\lambda } < 1400{\rm{nm}}) \end{array} \right. $
(3) 因此,在进行显微光声成像等过程中,需要注意控制聚焦激光的能量密度,使其控制在组织可以接受的范围内。如果超出MPE要求,则可以使用调制激光输出能量或使用光衰减片等方法来进行控制。
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首先,根据光声成像的原理公式(1)式可以看出,光声信号的强度除了与入射激光器的强度有关外,还与组织的光吸收系数μa成线性关系,即在同等条件下,μa越大,光声信号强度越大。因此,在光声成像时,应根据探测目标的吸收光谱,选取最为有利地强吸收峰对应波长作为光声激励的波长,以达到最佳的功能检测效果。例如常用的光声成像造影剂ICG, 由于其在血液中的吸收光谱主要在650nm~850nm范围内,因此多使用在该吸收光谱范围的波长作为其光声探测的光源,尤其是最强吸收峰的805nm。在多波长光声成像时,也应尽量选取多个吸收光谱峰值波长作为成像的波长。
同时,由于光波的特性(如频率、波长、能量密度等)、生物组织结构及其生物物理化学的多样性导致光与生物组织的相互作用十分复杂,光在组织中的穿透深度也受到较大的限制,进而限制了光声成像的探测深度。研究发现,在700nm~1400nm的近红外光波段内,生物组织对光的吸收和散射都是最小的,被称作组织光窗[32]。因此,在考虑组织吸收光谱特性的同时,应尽量选取在近红外波段内的吸收谱峰值波长来作为光声激励光源的波长,从而获得较高的探测深度。
光声成像激励光源的现状及选用
Status and selection of photoacoustic imaging exciting laser sources
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摘要: 随着光声成像技术研究的迅猛发展,其越来越多地被应用于生物医学成像及检测的各个方面。由于现有光声成像产品多受限于其激励光源,导致结构复杂、体积庞大、价格昂贵,限制了其进一步普及和推广。分析了光声成像对光源的限制和要求,总结了现有Nd:YAG、光学参量振荡器、半导体激光器及发光二极管等不同种类光声光源的现状和优劣,为光声成像技术研究和光声成像产品研制中对光声光源的选择提供相应的参考和指导。Abstract: With the rapid development of photoacoustic imaging, it is increasingly used in aspects of biomedical imaging and diagnosis. The existing photoacoustic imaging products are limited to further popularization and promotion because of the excitation light sources, which lead to complex structure, large volume and high cost. The limitations and requirements of light source in photoacoustic imaging were analyzed. The present situation, advantages and disadvantages of different types of photoacoustic sources, including Nd:YAG, optical parametric oscillator, semiconductor lasers and light-emitting diode were summarized. This work should be helpful to select appropriate light source for photoacoustic imaging technology research and photoacoustic imaging product development.
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Key words:
- lasers /
- exciting light source /
- photoacoustic imaging /
- semiconductor laser /
- LED
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图 3 利用OPO激光器获取的不同波长下的心血管图像[38]
图 4 多个脉冲调制半导体激光器集成的光声光源模块[42]
图 5 多波长LED光声成像系统原理示意图[48]
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