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新型光声传感及成像系统探测乳腺癌前哨淋巴结的基础研究
Basic research on photoacoustic sensing and imaging system for detecting sentinel lymph node in breast cancer
- 中国癌症杂志 2022年32卷第2期 页码：106-117
- 作者机构：
1. 山东第一医科大学（山东省医学科学院）, 山东 济南 250062
2. 山东省肿瘤防治研究院（山东省肿瘤医院）乳腺病中心,山东 济南 250117
3. 上海科技大学,信息科学与技术学院,混合成像系统实验室,上海 201210
4. 中国科学院上海微系统所与信息技术研究所,上海 200050
5. 中国科学院大学,北京 100049
- 作者简介：
[ "王永胜,二级教授、博士研究生导师,山东省肿瘤医院乳腺病中心主任,中国抗癌协会乳腺癌专业委员会副主任委员,中国抗癌协会国际医疗交流分会副主任委员;中国临床肿瘤学会乳腺癌专家委员会常委,中国医师协会肿瘤分会乳腺癌学组副组长,中华医学会肿瘤学分会乳腺癌学组委员,国家卫健委乳腺癌诊疗规范专家组成员,全球乳腺癌大会国际指导专家委员会成员,山东省抗癌协会靶向治疗分会主任委员。于国内率先开展乳腺癌保留乳房手术、前哨淋巴结活检替代腋窝淋巴结清扫术、乳腺病变微创诊断等研究,作为组长单位和首席专家,牵头开展了“中国临床早期乳腺癌前哨淋巴结活检替代腋窝清扫术的多中心研究”“乳腺癌内乳区前哨淋巴结活检术的多中心前瞻性临床验证研究”和“新型示踪技术引导乳腺癌内乳前哨淋巴结活检的多中心前瞻性临床研究”,研究成果已达到国际领先水平,并参与多项国际和国内乳腺癌Ⅲ期临床研究。以第一作者/通信作者发表论文100余篇,其中在SCI收录期刊上发表论文30余篇,出版专著（译著等）共4部,授权国家发明专利2项,获奖成果共5项,其中国家级1项、部（省）级4项,作为主要负责人承担国家级项目4项、部（省）级项目3项。" ]
- 基金信息：国家自然科学基金(81672638);山东省自然科学基金(ZR2021QH164)
DOI：10.19401/j.cnki.1007-3639.2022.02.002
中图分类号： R737.9收稿：2021-12-24，
纸质出版：2022-02-28
- 稿件说明：
移动端阅览
赵家贤, 江道淮, 丛斌斌, 等. 新型光声传感及成像系统探测乳腺癌前哨淋巴结的基础研究[J]. 中国癌症杂志, 2022,32(2):106-117.
Jiaxian ZHAO, Daohuai JIANG, Binbin CONG, et al. Basic research on photoacoustic sensing and imaging system for detecting sentinel lymph node in breast cancer[J]. China Oncology, 2022, 32(2): 106-117.
赵家贤, 江道淮, 丛斌斌, 等. 新型光声传感及成像系统探测乳腺癌前哨淋巴结的基础研究[J]. 中国癌症杂志, 2022,32(2):106-117. DOI： 10.19401/j.cnki.1007-3639.2022.02.002.
Jiaxian ZHAO, Daohuai JIANG, Binbin CONG, et al. Basic research on photoacoustic sensing and imaging system for detecting sentinel lymph node in breast cancer[J]. China Oncology, 2022, 32(2): 106-117. DOI： 10.19401/j.cnki.1007-3639.2022.02.002.
摘要
背景与目的：
前哨淋巴结活检（sentinel lymph node biopsy
SLNB）是临床淋巴结（lymph nodes
LN）阴性早期乳腺癌患者的标准分期技术
蓝染法联合核素法作为SLNB的标准方法仍有一定的局限性。应用新型荧光靶向示踪剂吲哚菁绿（indocyanine green
ICG）与利妥昔单抗（rituximab
RIT）偶联物（indocyanine green-rituximab
ICG-RIT）
搭建手持式光声信号传感系统（photoacoustic signal sensing s
ystem
PASS）及手持式光声成像（photoacoustic imaging
PAI）系统
探索其探测富集ICG-RIT的淋巴组织穿透深度
研究其定位前哨淋巴结的可行性。
方法
为探索PASS及PAI的组织穿透能力及定位能力
通过仿体实验将鸡胸组织覆盖于ICG-RIT染色的明胶仿体上模拟体内LN
通过PASS探测不同深度下ICG-RIT仿体的光声信号强度;同时设计人体组织试验—术前于患乳外上象限注射ICG-RIT
取荧光显像的LN于腋窝脂肪下
对比PASS、PAI及超声成像深度区别。通过SD大鼠后肢淋巴引流模型探索该技术作为SLNB的可行性
在SD大鼠后肢足垫皮下注射ICG-RIT
比较SD大鼠腘LN及髂LN的PASS及PAI定位区别。
结果
仿体实验结果显示
PASS探测鸡胸组织下ICG-RIT仿体呈现特征性单峰信号
且信号强度与组织深度成反比
最大探测深度平均达52.42 mm。人体组织试验结果显示
PASS探测腋窝脂肪下ICG-RIT染色LN最大探测深度达32.72 mm
对比鸡胸组织下6.25%浓度ICG-RIT染色仿体最大探测深度达39.72 mm;PAI探测腋窝脂肪下ICG-RIT染色LN深度达25 mm。SD大鼠模型结果显示
ICG-RIT停留于SD大鼠腘LN
在PASS中光声信号呈现特征性单峰曲线
PAI呈现特征性
&
#x0201C;热点
&
#x0201D;图
而髂LN未见明显光声信号
对比亚甲蓝则同时染色腘LN及髂LN。
结论
利用ICG-RIT的光声效应及靶向LN特性
通过手持式PASS及手持式PAI能准确定位SLN
同时有良好的组织穿透深度
具备良好的应用前景
但仍需进一步临床试验数据证实。
Abstract
Background and purpose:
Sentinel lymph node biopsy (SLNB) is a standard staging technique for patients with clinical lymph nodes (LNs) negative early breast cancer. Blue staining combined with radionuclide method as the standard method of SLNB still has certain limitations. In this study
a new fluorescent targeted tracer indocyanine green-rituximab (ICG-RIT) was applied
and a handheld photoacoustic signal sensing (PASS) system and a handheld photoacoustic imaging (PAI) system were built to explore the tissue penetration depth of LNs enriched with ICG-RIT
and to study the feasibility of the new system locating LNs.
Methods:
In order to study the tissue penetration ability of ICG-RIT and localization ability of PASS and PAI
three experiments were designed. For the phantom experiment
the PASS was used to detect the ICG-RIT dyed gelatin phantom which was covered with chicken breast tissue to simulate LNs
in vivo
. For the human tissue experiment
after ICG-RIT was injected into the breast before operation
the LNs enriched with ICG-RIT were excised during the surgery and detected by the fluorescence imaging system and gamma
probe detection system. The axillary LNs were covered with the axillary fat and detected by PASS
PAI and ultrasound imaging in sequence to compare the performance. For the rat lymph drainage model experiment
ICG-RIT was subcutaneously injected into the hind paw pad of SD rats to compare the PASS and PAI detection differences between popliteal LNs and iliac LNs.
Results:
The results of phantom experiment showed that ICG-RIT phantom under PASS detection showed the characteristic single-peak signal
and the signal amplitude was inversely proportional to the tissue depth
and the maximum detection depth was 52.42 mm on average. The human tissue experiment results showed that the maximum detection depth of ICG-RIT stained LNs under axillary fat detected by PASS was 32.72 mm
and the maximum detection depth of ICG-RIT stained phantom under 6.25% concentration of chicken breast tissue was 39.72 mm. The PAI detected ICG-RIT stained LNs in axillary fat up to 25 mm in depth. The results of SD rat model showed that ICG-RIT was collected by the popliteal LNs of SD rats
showing a monopolar curve on the PASS and a characteristic ‘hot spot’ on the PAI
and no obvious photoacoustic signal was found in iliac LNs. On the contrary
the methylene blue simultaneously stained popliteal LNs and iliac LNs.
Conclusion:
Taking advantage of the photoacoustic effect and targeting LNs characteristics of ICG-RIT
SLN can be accurately located by handheld PASS and handheld PAI with good penetration depth in tissue
showing potentials in clinical application. However
further clinical trial data are still needed to validate its clinical values.
关键词
Keywords
references
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