小型化光学超声传感器及其在光声成像中的应用进展(特邀)创刊六十周年特邀
1 引言
在光声成像(PAI)研究中,对成像深度和分辨率需求的不断增长促使了研究者们不断开发出具有高灵敏度、大带宽和宽接收角的超声传感器。在当前的光声显微成像(PAM)和光声计算断层扫描成像(PACT)中,广泛使用的是已经商业化的基于压电材料的超声换能器。从历史的发展来看,压电超声换能器最初被开发用于超声成像时,需要工作在脉冲回波模式中频繁地产生和接收超声波信号。然而PAI与医用超声成像的成像场景不同,超声波通常由脉冲激光或脉冲微波激发产生[1],因此科研者们开始认识到压电超声换能器或许并非PAI的最佳选择。同时,压电超声换能器的不透明性可能会影响PAI中的光学激发,增加光学校准的复杂性并在光声耦合时引起信号损失。此外,超声传感器的微型化也对光声内窥镜(PAE)和PACT等应用较为重要,然而由于压电超声换能器的灵敏度与感应面积的平方根成比例下降[2],直接减小压电超声换能器的尺寸会极大地降低传感器的性能。目前,研究者们或通过研究透明材料[3],或通过开发电容微机械超声换能器[4-5]来尝试解决压电超声换能器面临的这些问题。然而迄今为止,改进后的器件所呈现出的灵敏度和带宽等性能表现仍然无法满足临床应用对PAI的指标要求。
相较于电学探测,光学探测具有高精度和高灵敏度的优势。近数10年来,研究者们积极地开发着光学超声传感器,以期最终替代PAI中的压电超声换能器。与压电超声换能器相比,光学超声传感器具有较大的工作带宽和与尺寸几乎无关的高灵敏度。凭借这些优势,光学超声传感器在推动PAI的应用开展方面具有巨大潜力。迄今为止,多种用于光学超声探测的方法已被提出,与其技术原理相关的综述文章可参见文献[1,6]。本文重点介绍使用微型光学谐振腔的超声传感器,该类型的光学超声传感器具有高灵敏度、微型化等特点,展现出其作为新一代敏感和宽带超声传感器的巨大潜力。接着,对光学超声传感器阵列进行并行寻址的最新方法进行了简要介绍。最后,对这些光学超声传感器在开展PAI的最新应用进行了回顾,并讨论了光学超声传感器的未来发展趋势。
2 基于光学微谐振腔的光学超声传感器
由于光学测量通常具有高灵敏、高准确度的特点,各类光学超声传感器的基本思想均是通过测量光学参数的时域变化来反映超声波的时域信号强度[1]。简要来说,超声波是一种物质波,其存在会引起所处环境光学性质的变化,当具有时变效应的超声波信号存在时,所监测的光学信号也会展现相应的时变特性。相比于压电超声换能器依赖于超声波能量到电能的直接转换,光学超声传感器依赖的是从超声波到光波再到电能的转换。因此,光学超声传感器的探测极限通常由光电探测器的探测极限决定。在光学超声传感器的发展历程中,存在着多种实现形式。例如,通过记录超声波穿过两种不同介质界面时引起的界面反射光强度的波动,能够实现随时间变化的超声波信号强度的探测[7]。为了提高传感器的探测灵敏度,科研者们在界面处镀上金属-介电涂层以激发表面等离子体共振,进而增强光与超声波的相互作用[8-9]。该类型的光学超声传感器的带宽高达180 MPa[10-11],有利于提高PAM的轴向分辨率。除此之外,还可以利用超声波存在时的光束偏转程度来反映超声波信号的强度[12-13]。这种偏转通常出现在声光偏转器中,可以使用对位置敏感的光学探测器定量测量。该探测器能够有效地表征超声波[14-15],除了能够检测超声波引起的位置变化之外,还可以检测超声波引起的相位及偏振变化[16]。
为了提高传感器的探测灵敏度,也可以通过光学干涉系统来测量光路中超声波引起的相位变化。在早期的研究中,迈克尔孙干涉仪和马赫-曾德干涉仪(MZI)已经证明了它们具备探测超声波的能力[17-18]。研究者们也尝试将光学谐振腔与光纤系统耦合来探测超声波信号,搭建了大带宽、高灵敏度的PAI系统[19-21]。光学谐振腔通过将光束限制在较小的空间内以增强光与超声波的相互作用,能够有效提高探测的灵敏度。近年来,微纳加工工艺的发展使得具有高品质因数的微米甚至纳米尺度的光学谐振腔成为可能。因此,结合了微型光学谐振腔和光学干涉测量方法的光学超声传感器通常具有高灵敏度、微型化等优点。接下来,重点描述3种基于不同微型光学谐振腔的光学超声传感器:法布里-珀罗谐振腔[22-27]、π相移布拉格光栅谐振腔(π-BGs)[28-34]和微环谐振器[35-37]。
2.1 法布里-珀罗谐振腔
早期的法布里-珀罗干涉仪将探测光束置于两个平面镜之间,由于超声波的存在会改变谐振腔的光程,造成谐振腔的共振频率随之改变,因此通过记录透射或反射光束的瞬态强度变化就能够实现超声波信号的探测,目前基于该类光学干涉仪的超声传感器可以实现低至50 Pa的探测灵敏度和高达40 MHz的探测带宽[24]。尽管该传感器的设计与制造对其实现阵列化具有一定便利性[23,38],但探测光束的往返振荡会引起横向偏移,导致高度集成的光学约束难以实现,进而降低了光学和超声波的探测灵敏度[27]。
近几年,Guggenheim等[27]设计了一种微型的平凹光学谐振腔,通过使用波前匹配的凹面镜来增强光束在腔体内来回反射时的光学约束来大幅提高超声波探测灵敏度。该光学超声传感器的示意图如
图 1. 基于平凹光学谐振腔的超声传感器[27]。(a)基于平凹光学谐振腔的超声传感器示意图;(b)在单模光纤顶端形成的超声传感器示意图;(c)16 μm腔长的传感器的频率响应曲线;(d)16 μm腔长的传感器的方向角响应分布图;(e)16 μm腔长的传感器的方向角响应与直径为2 mm的圆盘形传感器的理论响应对比图
Fig. 1. Plano-concave optical microresonator optical ultrasound sensor[27]. (a) Schematic of the plano-concave optical microresonator ultrasound sensor; (b) schematic of the sensor formed on the tip of a single mode optical fiber; (c) frequency response plot of the sensor with a cavity thickness of 16 μm; (d) direction angle response diagram of the sensor with a cavity thickness of 16 μm; (e) direction angle response of the sensor with a cavity thickness of 16 μm compared to the theoretical response of a disk-shaped sensor with a 2-mm diameter
2.2 π-BGs谐振腔
基于π-BGs的光学超声传感器本质上是在光纤或波导上加工而成的一维谐振腔体。在这些微型谐振腔中,光被限制在比布拉格光栅物理尺寸更小的维度内。早期该类传感器的灵敏度和带宽分别可达到100 Pa和77 MHz[30-31]。然而,该类传感器是一种线性探测器,相对于点探测器需要更复杂的图像重建算法。
最近,Shnaiderman等[33]基于绝缘硅片工艺开发了近乎理想点状的传感器,该传感器具有光波导上的微型π-BGs,被称为硅波导标准检测器(SWED),感应面积仅为220 nm×500 nm,每面积灵敏度比压电超声换能器高出100000000倍,其示意图及其工作原理如
图 2. 基于π-BGs的点状SWED[33]。(a)SWED读出系统示意图;(b)宽带超声点源线性扫描布拉格光栅侧面波纹深度为40 nm的SWED所获得的SWED3的空间响应图,扫描路径平行于芯片表面的短维度;(c)宽带超声点源线性扫描水听器所获得的直径为0.5 mm的针状水听器的空间响应图;(d)在宽带超声点源作用下,4个不同SWED的时间响应图;(e)与图2(d)信号对应的4个SWED的频谱响应图
Fig. 2. Point-like SWED based on π-BGs[33]. (a) Diagram of the SWED read-out system; (b) spatial response of SWED3 acquired by scanning the SWED with a 40-nm corrugation depth on the sides of the Bragg grating linearly over a broadband ultrasound point source, the scanning trajectory is aligned with the short dimension of the chip facet; (c) spatial response of a needle hydrophone with a diameter of 0.5 mm acquired by scanning the hydrophone over a broadband ultrasound point source; (d) temporal responses of four different SWEDs when subjected to a broadband ultrasound point source; (e) spectral responses of four SWEDs to the signals in Fig. 2 (d)
SWED包含一个硅波导,可分为4个部分:银层、间隔层、腔体和布拉格光栅。当连续泵浦激光被限制在腔体内时,其波长被调谐到非共振最陡斜坡处,当入射的超声波引起腔体的共振变化时,光电二极管所测量的反射光强的变化可表示为时变的超声波信号。该工作中展示了4个间隔长度分别为26 μm、14 μm、9 μm和3.5 μm的SWED的工作性能,其中,
Hazan等[34]在相同的硅光子学平台上开发了一种基于微型化π-BGs的光学超声传感器,如
图 3. 基于硅光体系的超声探测器[34]。(a)硅光子层结构及带光栅耦合器的π-BG示意图;(b)光纤粘合前硅光子芯片照片;(c)组装后镀金的硅光子芯片照片;(d)光学读出系统示意图;(e)谐振腔光谱图;(f)超声引起的波长变化图;(g)谐振腔的光学输出信号图;(h)在系统输出处采样的差分电压信号图;(i)点源及其二维切片重建图;(j)分辨两个不同间隔距离点源的模拟图
Fig. 3. Silicon-photonics acoustic detector[34]. (a) Schematic of the layer structure of silicon-photonics and the configuration of π-BG with grating couplers; (b) photograph of the silicon-photonics chip before fiber bonding; (c) photograph of the assembled silicon-photonics chip with a gold coating; (d) schematic of the optical readout system; (e) spectrum plot of the resonant cavity; (f) plot of ultrasound-induced wavelength variation; (g) plot of the optical output signal from the resonator; (h) plot of differential voltage signal, sampled at the output of the system; (i) reconstruction image of the point source and corresponding 2D slices; (j) separation simulation of two point sources at different distances
2.3 微环谐振腔
微环谐振腔具有高品质因子、微型化和光透明等优势[35-36,39-41],迄今为止,文献中已经报道了使用聚合物[36,39]、硅[42],甚至硫化物[43]等材料制备的基于微环的光学超声传感器。在各个性能指标方面,Ling等[44]和Xie等[45]开发的传感器具有高达105的品质因子,Zhang等[46]开发的传感器响应频率带宽高达350 MHz,Westerveld等[42]开发的高灵敏度的传感器NEP低至1.3 mPaHz-1/2,Li等[35]开发的传感器接收角度较大,可达±30°。由于微环谐振腔所具有的众多优点,该类传感器在PAI领域备受研究者们的青睐。
Westerveld等[42]结合硅光技术开发了一种基于微环谐振腔的光学超声传感器,该传感器大小约为20 µm,在3~30 MHz的频率范围内NEP可保持在1.3 mPaHz-1/2以下。基于微环谐振腔的光学超声传感器的工作原理如
图 4. 结合了硅光技术的微环谐振器光学超声传感器[42]。(a)传感器示意图;(b)带有微小间隙的分裂脊波导示意图;(c)不同激光波长下的输出光谱;(d)传感器时间响应曲线;(e)传感器的灵敏度(左轴)和噪声幅度谱密度(右轴)曲线;(f)由10个传感器构成的一维阵列的传输光谱
Fig. 4. Optical ultrasound sensor utilizing the micro-ring resonator in silicon photonics[42]. (a) Schematic of the sensor; (b) schematic of the split-rib waveguide featuring a small gap; (c) output spectrum at different laser wavelengths; (d) temporal response plot of the sensor; (e) plot of the sensor sensitivity (left axis) and noise amplitude spectral density (right axis) of the sensor; (f) transmission spectrum of a one-dimensional array composed of ten sensors
2.4 传感器阵列并行寻址
大多数基于微型谐振腔的光学超声传感器都是单元素的,而在实际应用中多元素的传感器阵列可以极大地提高成像速度、提升成像视场和接收角度。尽管法布里-珀罗干涉仪本身是一个二维传感器阵列[23,38],但该类传感器阵列的并行寻址通常涉及光电探测器阵列的使用,大幅增加了电路复杂性且容易造成信号串扰。类似地,基于光纤光学的探测器阵列也需要相当复杂的寻址系统[47-50]。2008年,Maxwell等[36]开发了首个片上集成的传感器阵列,其包含4个微环。然而由于当时制造的光学谐振腔的品质因子相对较低,相邻共振频率之间存在较大程度的频谱重叠。因此,如何实现4个微环的并行工作仍然是一个挑战。2021年,Westerveld等[42]基于硅光技术开发了具有高品质因数的微环阵列,包含10个微环且相邻元素共振频率之间有明显的间隔。然而,该系统只有一个激光和一个光电探测器,一次只允许单个微环传感器进行工作。为了实现并行寻址,Zhang等[46]设想了一种基于波分复用的寻址方式,该方法相当繁琐,需要足够数量的光源-探测器对[42]或者频率扫描源[48]。Hazan等[50]则使用相位调制脉冲来实现对超声波的多通道并行检测,然而系统最多仅可容纳4个微环,且每个检测通道仍然需要一个光电探测器,极大地增加了系统的复杂性。
Pan等[43]在对光学超声传感器阵列进行并行寻址方面取得了新的进展,开发了数字光学频率梳(DOFC)技术,可以稳定、灵活和可调谐地探测传感器阵列的传输光谱。在实验中该研究团队制备了一个包含15个微环的光学超声传感器阵列,并将该传感器阵列耦合到单总线波导上。这些微环传感器的频率响应带宽高达175 MHz(-6 dB)、NEP低至2.2 mPaHz-1/2或7.1 Pa(20 MHz范围内)、接收角度为±30°(25 MHz时为-3 dB)、尺寸为0.85 μm×40 μm×40 μm。使用传感器阵列实现并行寻址的实验装置如
图 5. 基于微环传感器阵列的并行寻址原理[43]。(a)成像系统的实验设置图;(b)空状态下,传感器阵列随时间变化的传输光谱图;(c)超声波调制传感器阵列时,随时间变化的传输光谱图;(d)每个微环传感器随时间变化的超声波信号强度
Fig. 5. Parallel addressing principle based on micro-ring sensor array[43].(a) Experimental setup of the imaging system; (b) the recorded time-varying transmission spectrum of the sensor array under null conditions; (c) the recorded time-varying transmission spectrum of the sensor array modulated by ultrasound; (d) the time-varying reconstructed ultrasound signal of each micro-ring sensor
3 光学超声传感器的成像应用
凭借其卓越的性能,光学超声传感器已被初步用于PAI应用中,如在PAM及PAE[51-53] 中对单细胞[53]、小鼠耳朵[45,54]和小鼠大脑[55]等进行高分辨率成像,以及在成像深度高达8 mm的深层生物组织中[56]对活体斑马鱼全身的PACT成像[43]。诚然,相比于使用已经商用化的压电超声传感器而言,基于光学超声传感器的活体成像演示仍然较少。这主要是因为该研究仍处于早期工艺摸索和研发阶段,传感器及其成像系统的鲁棒性仍有待提高。我们相信,随着制备工艺不断成熟,未来将会涌现出更多的基于光学超声传感器的活体PAI实验。本小节着重介绍两个特别适合于微型光学超声传感器的代表性成像应用。
3.1 微型前视内窥成像
为了推动PAI的临床应用,目前有大量的工作关注于如何推进PAI的工作深度[57-58]。其中,一个重要的研究热点集中在微型PAE设备的开发上,可在微创情况下评估前列腺癌、结直肠癌和冠状动脉等疾病,亦可在腹腔镜手术中协助指导介入手术[52]。为满足PAE对微型化超声传感器的需求,研究者们开发了一种微型前视三维光学超声传感器,包括一个带有法布里-珀罗传感器的相干光纤束[24,59-60]。具体来说,该传感器由一个刚性的76 mm长、3.2 mm直径的光纤束组成,具有50000个纤芯,可以通过点扫描的方式来实现寻址,如
图 6. 全光学前视PAE传感器[52]。(a)传感器示意图;(b)远端放大图;(c)沉积在光纤束远端的法布里-珀罗传感器,由夹在聚对二氯甲苯间隔层之间的两个介电镜涂层组成
Fig. 6. All-optical forward-viewing photoacoustic endoscopy sensor[52]. (a) Schematic of the sensor; (b) magnified visualization of the distal end; (c) the Fabry-Pérot sensor deposited on the distal end of the fiber bundle consists of two dielectric mirror coatings that are sandwiched between a Parylene C spacer layer
Ansari等[52]利用该PAE传感器,结合590 nm的激发脉冲光源对离体鸭胚进行了成像,如
图 7. 体外鸭胚的光声图像[52]。(a)禽类胚胎脉管系统示意图;(b)(c)同一胚胎在0~200 µm深度范围的两个区域的x-y最大强度投影;(d)(f)在0~1.5 mm深度范围内,分别与图7(b)、(c)相同的x-y最大强度投影;(e)(g)y-z最大强度投影
Fig. 7. Photoacoustic images of an ex vivo duck embryo[52]. (a) Schematic of an avian embryonic vasculature; (b)(c) maximum intensity projections of x-y cross-sectional images, covering a depth range from 0 to 200 µm, generated for two distinct regions of the same embryo; (d)(f) maximum intensity projections of x-y cross-sectional images, covering a depth range from 0 to 1.5 mm, generated for the same two regions as in Fig. 7 (b),(c) respectively; (e) (g) maximum intensity projections of y-z cross-sectional images
该PAE传感器还被用于对五周大的小鼠腹部皮肤微血管进行成像。三维图像数据集在两个不同区域的x-y和x-z的最大强度投影如
图 8. 小鼠腹部皮肤微血管的光声图像[52]。(a)(b)0~2 mm深度范围的两个区域的x-y最大强度投影;(c)(d)同一区域的x-z最大强度投影
Fig. 8. Photoacoustic images of mouse abdominal skin microvasculature[52]. (a) (b) The maximum intensity projection of x-y in two areas within a depth range of 0‒2 mm; (c) (d) maximum intensity projection of x-z in the same region
与直径数毫米的光纤束比起来,使用直径较小的多模光纤(MMFs)来开发微型PAE传感器更具前景。Zhao等[61]通过使用直径为140 µm的MMF来传递激发光,结合高灵敏度的光学超声传感器来探测光声信号。通过数字微镜器件进行波前调控,科研者们实现了MMF末端焦点光斑的快速扫描,获取了小鼠红细胞的光声图像。其中,对于100 µm直径大小的图像,采集速度约为3 frame/s,图像分辨率达到系统光学衍射极限,约为1.2 µm。由于该传感器可提供亚细胞的空间分辨率图像,包含了组织丰富的功能、分子和微观结构等信息,可以被用来实时协助和指导微创手术。
3.2 植入式光学超声传感器的体内皮质成像
微型光学超声传感器在植入活体动物的大脑中时具有优势。2019年,Li等[55]开发了一种低成本的软纳米压印光刻方法,制造了基于微环谐振腔的一次性光学超声传感器。通过将传感器安置到慢性颅窗(CCW)的内表面,实现了超声传感CCW(usCCW),并对活体小鼠的皮质血管结构进行了超过28天的监测。
图 9. 使用usCCW进行体内PAM皮质成像[55]。(a)小鼠开颅后在颅骨上植入usCCW的示意图;(b)通过usCCW进行光学扫描的示意图;(c)沿图9(b)突出显示的横截面进行光学激发和超声检测的结构图;(d)微环谐振器获得的皮质区域的明场PAM图像;(e)同一区域的深度编码的PAM最大强度投影图;(f)血管方向和皮质曲率的3D PAM图像;(g)图9(d)和图9(e)中虚线框指定的出血区域的PAM图像;(h)沿图9(g)中绿色虚线的B扫描PAM图像;(i)出血区域下隐藏的血管的PAM图像,比例尺,(a)(b)0.5 mm,(g)(i)200 µm
Fig. 9. In vivo PAM cortical imaging using a usCCW[55]. (a) Schematic of the mouse skull with the usCCW implantation following craniotomy; (b) schematic of optical scanning conducted through the usCCW; (c) optical excitation and ultrasonic detection configuration along the delineated cross-sectional region shown in Fig. 9(b); (d) brightfield optical microscopy image obtained through the micro-ring resonator in the cortical region; (e) depth-encoded maximum intensity projection image captured via PAM of the identical area; (f) three-dimensional PAM image showcasing the vascular directions and cortical curvature; (g) PAM image showcasing the hemorrhage area delineated by the dashed box in Fig. 9(d), (e); (h) PAM B-scan image showcasing the area delineated by the green dashed line in Fig. 9(g); (i) PAM image showcasing the concealed blood vessels underneath the hemorrhage region, scale bars, (a) (b) 0.5 mm, (g) (i) 200 µm
研究者们还使用usCCW对活体小鼠大脑进行了长期活体PAM成像,如
图 10. 通过usCCW对皮质区域进行长期的PAM成像[55]。(a)植入透明usCCW后,在饲养笼中自由活动的小鼠照片;(b)成像期间被固定在显微镜下的小鼠照片;(c)植入了透明usCCW后的大脑皮层的放大图;(d)28天内测得的品质因数,基本没有下降;(e)28天内同一区域的大脑皮质血管的PAM图像的最大幅度投影;(f)(g)(h)第0天和第2天、第0天和第14天、第14天和第28天的皮质脉管系统的比较
Fig. 10. PAM cortical imaging through the usCCW over an extended period[55]. (a) Photograph of a mouse inside a rearing cage, at liberty to move following the implantation of transparent usCCW; (b) photograph obtained during imaging of the mouse fixed under the microscope; (c) magnified image of the cerebral cortex after the implantation of transparent usCCW; (d) hardly reduced quality factors measured during a span of 28 days; (e) maximum amplitude projections of PAM images of cortical vasculature captured in the identical region during a span of 28 days; (f) (g) (h) comparison of the measured cortical vasculature between day 0 and day 2, day 0 and day 14, and day 14 and day 28
4 结论
PAI在超声探测方面面临的挑战与机遇,极大地引起了研究者们对光学超声探测方案的兴趣。与压电超声传感器相比,基于微型谐振腔的光学超声传感器的主要优势在于保持微小尺寸的同时,而不牺牲灵敏度。然而,近期也有研究者们评论道[62],光学超声传感器目前所展现出来的性能优势并不足以让其在各个PAI领域都替代已商业化的压电超声传感器。诚然,由于PAM成像深度较浅且多数时候仅需要单个传感器,光学超声传感器的大带宽优势能够通过提供更优的轴向分辨率而得到体现。然而,PACT通常需要使用传感器阵列来实现高速成像,光学超声传感器在并行寻址方面的缺失和问题此时便展现出来。同时,PACT由于成像深度较深的原因仅需对低频超声波进行探测,光学超声传感器的大带宽优势此时显得毫无用武之地。此外,由于超声波的探测通常处于远场,传感器阵列中的元素只需跟超声波远场时的半波长相匹配,并没有对于微米甚至纳米尺度片上传感器的需求。
不管怎样,研究者们在光学超声传感器方面取得的创新成果不断突破着超声波的探测极限,尽管仍然存在着许多问题和不确定因素,这些研究成果最终定将在推动PAI在实现更深和更高分辨率成像方面取得巨大的成果。
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Article Outline
邱显坤, 赵佳玉, 沈乐成. 小型化光学超声传感器及其在光声成像中的应用进展(特邀)[J]. 激光与光电子学进展, 2024, 61(2): 0211032. Xiankun Qiu, Jiayu Zhao, Yuecheng Shen. Miniaturized Optical Ultrasound Sensors and their Applications in Photoacoustic Imaging (Invited)[J]. Laser & Optoelectronics Progress, 2024, 61(2): 0211032.