高频超声和光学相干断层成像可在体监测裸鼠黑素瘤的动态发展过程
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摘要
目的探讨高频超声和光学相干断层成像(OCT)在监测皮肤黑素瘤生长过程中的成像效果。方法将20只4周龄的裸鼠随机分为实验组(n=16)与对照组(n=4)。实验组:将0.2 mL A375人源皮肤黑素瘤细胞悬液经皮下种植于裸鼠背部;对照组:将等量的培养液经皮下种植于裸鼠背部。自接种后起,每天对裸鼠进行大体观察、小动物高频超声成像以及OCT成像,对所得图像进行量化分析,并记录肿瘤成瘤时间、肿瘤大小、体积、长径、厚径等信息,接种后第24天解剖裸鼠,切取肿瘤块进行病理检查。结果皮肤黑素瘤接种成功率为87.5%,结果经HE染色证实。OCT比高频超声更早探测到肿瘤。随着肿瘤的生长,在高频超声图像中可见点状或带状强回声信号,在OCT图像中出现真皮上层的扁平化,并且在高频超声与OCT中,CNR均逐步增强(P<0.05)。生长曲线图显示,与高频超声相比,OCT对厚径的测量更灵敏,测量结果比较差异有统计学意义(P<0.05)。结论高频超声和OCT可在体监测皮肤黑素瘤的动态发展过程,且在不同发展阶段,成像效果不同。高频超声和OCT在肿瘤生长的不同阶段的影像学表现,可在研究肿瘤动态发展过程中,对不同影像模态的选择提供参考依据。
Objective To investigate the application of high-frequency ultrasound(HFUS) and optical coherence tomography(OCT) for monitoring the progression of cutaneous melanoma(CM) in nude mice. Methods Twenty 4-week-old nude mice were randomly divided into CM group(n=16) and control group(n=4). In CM group, A375 cell suspension were injected subcutaneously on the back of the nude mice, and only culture medium was injected in the control group. The tumor growth was monitored by gross observation and with HFUS and OCT on a daily basis. The tumor formation rate, time, and size were recorded and melanoma visibility was assessed quantitatively using the contrast-to-background-noise ratio(CNR). Twentyfour days after cell implantation, the tumors were dissected for pathological examination. Results The tumor formation rate was 87.5% in CM group. OCT detected tumor formation at an earlier time than HFUS. With the growth of the tumor, HFUS detected spots or bands of strong echoes, and flattening of the upper dermis could be observed in OCT; the of HFUS and OCT were obviously enhanced over time(P<0.05). The tumor growth curve showed that OCT was more sensitive for measurement of the tumor thickness than HFUS. The length, depth and volume of the tumors measured by HFUS were significantly greater than those measured by OCT(P<0.05). Conclusion HFUS and OCT can monitor the dynamic development of cutaneous melanoma in nude mice, and their imaging performance differs in different stages of tumor development.
Objective To investigate the application of high-frequency ultrasound(HFUS) and optical coherence tomography(OCT) for monitoring the progression of cutaneous melanoma(CM) in nude mice. Methods Twenty 4-week-old nude mice were randomly divided into CM group(n=16) and control group(n=4). In CM group, A375 cell suspension were injected subcutaneously on the back of the nude mice, and only culture medium was injected in the control group. The tumor growth was monitored by gross observation and with HFUS and OCT on a daily basis. The tumor formation rate, time, and size were recorded and melanoma visibility was assessed quantitatively using the contrast-to-background-noise ratio(CNR). Twentyfour days after cell implantation, the tumors were dissected for pathological examination. Results The tumor formation rate was 87.5% in CM group. OCT detected tumor formation at an earlier time than HFUS. With the growth of the tumor, HFUS detected spots or bands of strong echoes, and flattening of the upper dermis could be observed in OCT; the of HFUS and OCT were obviously enhanced over time(P<0.05). The tumor growth curve showed that OCT was more sensitive for measurement of the tumor thickness than HFUS. The length, depth and volume of the tumors measured by HFUS were significantly greater than those measured by OCT(P<0.05). Conclusion HFUS and OCT can monitor the dynamic development of cutaneous melanoma in nude mice, and their imaging performance differs in different stages of tumor development.
引文
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[26]Botar-Jid CM,Cosgarea R,Bolboaca SD,et al.Assessment of cutaneous melanoma by use of very-high-frequency ultrasound and real-time elastography[J].AJRAm J Roentgenol,2016,206(4):699-704.
[27]Andrekute K,Linkeviute G,Raitis R,et al.Automatic differential diagnosis of melanocytic SkinTumors using ultrasound data[J].UltrasoundMed Biol,2016,42(12):2834-43.
[28]Gambichler T,Regeniter P,Bechara FG,et al.Characterization of benign and malignant melanocytic skin lesions using optical coherence tomography in vivo[J].JAmAcad Dermatol,2007,57(4):629-37.
[29]Moraes PT,Cohen MP,Gomes EE,et al.Optical coherence tomography(OCT)features of nevi and melanomas and their association with intraepidermal or dermal involvement:apilot study[J].JAmAcad Dermatol,2015,73(2):315-7.
[30]Welzel J,Reinhardt C,Lankenau E,et al.Changes in function and morphology of normal human skin:evaluation using optical coherence tomography[J].Br J Dermatol,2004,150(2):220-5.
[31]许建树,龚玮,邹健,等.皮肤光学相干成像技术[J].中国激光医学杂志,2016(2):97-102.
[32]Meyer N,Lauwers-Cances V,Lourari S,et al.High-frequency ultrasonography but not 930-nm optical coherence tomography reliably evaluates melanoma thickness in vivo:a prospective validation study[J].Br J Dermatol,2014,171(4):799-805.
[33]Malik B,Terry R,Wiskin J,et al.Quantitative transmission ultrasound tomography:imaging andperformance characteristics[J].Med Phys,2018,45(7):3063-75.
[34]Bhatt KD,Tambe S,Jerajani HR,et al.Utility of high-frequency ultrasonography in the diagnosis ofbenign and malignant skin tumors[J].Indian J DermatolVenereol Leprol,2016,83(2):162-82.
[2]Li Z,Wang CF,Deng HH,et al.Robust photodynamic therapy using5-ALA-Incorporated nanocomplexes cures metastatic melanoma through priming of CD4(+)CD8(+)double positive T cells[J].Advanced Sci,2019,6(5):1802057.
[3]CSCO Melanoma expert committee.Guidelines for the diagnosis and treatment of melanoma in China(2011)[J].Chin clin Oncol,2012,17(2):159-71.
[4]Siegel RL,Miller KD,Jemal A.Cancer statistics,2016[J].CACancer J Clin,2016,66(1):7-30.
[5]Kucinskiene V,Samuleniene D,Gineikiene AA,et al.Preoperative assessment of skin tumor thickness and structure using 14-MHz ultrasound[J].Medicina(Kaunas),2014,50(3):150-5.
[6]Jasaitiene D,Valiukeviciene S,Linkeviciute G,et al.Principles of high-frequency ultrasonography for investigation of skin pathology[J].J EurAcad DermatolVenereol,2011,25(4):375-82.
[7]Jid CB,Bolboaca SD,Cosgarea RA,et al.Doppler ultrasound and strain elastography in the assessment of cutaneous melanoma:preliminary results[J].Med Ultrason,2015,17(4):509-14.
[8]Pilat P,Borzecki A,Jazienicki MA.Skin melanoma imaging using ultrasonography:a literature review[J].Postepy Dermatolog,2018,35(3):238-42.
[9]于瑞星,薛珂,沈雪,等.高频超声在皮肤黑素瘤的临床应用价值[J].皮肤科学通报,2018,35(2):216-20.
[10]Huang D,Swanson EA,Lin CP,et al.Optical coherence tomography[J].Science,1991,254(5035):1178-81.
[11]Schmitz L,Reinhold U,Bierhoff E,et al.Optical coherence tomography:its role in daily dermatological practice[J].J Dtsch Dermatol Ges,2013,11(6):499-507.
[12]Boone M,Suppa M,Dhaenens F,et al.In vivo assessment of optical properties of melanocytic skin lesions and differentiation of melanoma from non-malignant lesions by high-definition optical coherence tomography[J].Arch Dermatol Res,2016,308(1):7-20.
[13]Wijesinghe RE,Park K,Kim D,et al.In vivo imaging of melanomaimplanted magnetic nanoparticles using contrast-enhanced magnetomotive optical Doppler tomography[J].J Biomed Opt,2016,21(6):64001.
[14]Pires L,Demidov V,Vitkin IA,et al.Optical clearing of melanoma in vivo:characterization by diffuse reflectance spectroscopy and optical coherence tomography[J].J Biomed Opt,2016,21(8):81210.
[15]夏扬.基于频域光学相干层析术的人体皮肤高分辨率光学断层成像研究[D].南京:南京理工大学,2010.
[16]Hinz T,Ehler LK,Voth H,et al.Assessment of tumor thickness in melanocytic skin lesions:comparison of optical coherence tomography,20-MHz ultrasound and histopathology[J].Dermatology,2011,223(2):161-8.
[17]Ud-Din S,Foden P,Stocking K,et al.Objective assessment of dermal fibrosis in cutaneous scarring:using optical coherence tomography,high frequency ultrasound and immuno-histo-morphometry of human skin[J].Br J Dermatol,2019,25(3):17739.
[18]Sassaroli E,Crake C,Scorza A,et al.Image quality evaluation of ultrasound imaging systems:advanced B-modes[J].J Appl Clin Med Phys,2019,20(3):115-24.
[19]Mishra T,Mohan M,Chakravarty M,et al.Zinc oxide nanoparticles(ZnONPs)as contrast agent for imaging of animal tissue using swept source optical coherence tomography(SSOCT)[J].Optik(Stuttg),2019,176(2):302-8.
[20]Wassef C,Rao BK.Uses of non-invasive imaging in the diagnosis of skin cancer:an overview of the currently available modalities[J].Int J Dermatol,2013,52(12):1481-9.
[21]Marghoob AA,Swindle LD,Moricz CZ,et al.Instruments and new technologies for the in vivo diagnosis of melanoma[J].J Am Acad Dermatol,2003,49(5):777-97.
[22]Guitera P,Menzies SW.State of the art of diagnostic technology for early-stage melanoma[J].Expert Rev Anticancer Ther,2011,11(5):715-23.
[23]谢雄风,高金平,张学军.高频超声在皮肤科的应用[J].中华皮肤科杂志,2017,50(10):768.
[24]Wortsman X,Wortsman J.Clinical usefulness of variable-frequency ultrasound in localized lesions of the skin[J].J Am Acad Dermatol,2010,62(2):247-56.
[25]周璟.高频超声的常见皮肤肿瘤表现及在基底细胞癌术前评估的应用研究[D].天津:天津医科大学,2016.
[26]Botar-Jid CM,Cosgarea R,Bolboaca SD,et al.Assessment of cutaneous melanoma by use of very-high-frequency ultrasound and real-time elastography[J].AJRAm J Roentgenol,2016,206(4):699-704.
[27]Andrekute K,Linkeviute G,Raitis R,et al.Automatic differential diagnosis of melanocytic SkinTumors using ultrasound data[J].UltrasoundMed Biol,2016,42(12):2834-43.
[28]Gambichler T,Regeniter P,Bechara FG,et al.Characterization of benign and malignant melanocytic skin lesions using optical coherence tomography in vivo[J].JAmAcad Dermatol,2007,57(4):629-37.
[29]Moraes PT,Cohen MP,Gomes EE,et al.Optical coherence tomography(OCT)features of nevi and melanomas and their association with intraepidermal or dermal involvement:apilot study[J].JAmAcad Dermatol,2015,73(2):315-7.
[30]Welzel J,Reinhardt C,Lankenau E,et al.Changes in function and morphology of normal human skin:evaluation using optical coherence tomography[J].Br J Dermatol,2004,150(2):220-5.
[31]许建树,龚玮,邹健,等.皮肤光学相干成像技术[J].中国激光医学杂志,2016(2):97-102.
[32]Meyer N,Lauwers-Cances V,Lourari S,et al.High-frequency ultrasonography but not 930-nm optical coherence tomography reliably evaluates melanoma thickness in vivo:a prospective validation study[J].Br J Dermatol,2014,171(4):799-805.
[33]Malik B,Terry R,Wiskin J,et al.Quantitative transmission ultrasound tomography:imaging andperformance characteristics[J].Med Phys,2018,45(7):3063-75.
[34]Bhatt KD,Tambe S,Jerajani HR,et al.Utility of high-frequency ultrasonography in the diagnosis ofbenign and malignant skin tumors[J].Indian J DermatolVenereol Leprol,2016,83(2):162-82.
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