Feasibility Study on Intraoperative Lugol's Iodine Enhanced Micro-CT Imaging Accelerated by Ultrasound for Specimen of Oral Squamous Cell Carcinoma

doi:10.13701/j.cnki.kqyxyj.2023.11.009

Abstract

Abstract: Objective: To evaluate the feasibility of Lugol's iodine enhanced micro-CT imaging accelerated by ultrasound for the oral squamous cell carcinoma (OSCC) samples. Methods: Firstly, ultrasound (3W) was applied to accelerate Lugol's iodine (1%, 3%, and 5%) staining of Cal-27 cell line for 5, 10, and 15 min, respectively. The average optical density (AOD) was used to evaluate the staining difference. Then, thirty-six BALB/C nude mice [8 weeks old, (25±2) g] were randomly divided into ultrasound group and non-ultrasound group, which were stained by 1%, 3%, and 5% Lugol's iodine respectively. Micro-CT imaging and CT quantitative analysis were performed at 0.5 h and 1 h after staining. Finally, four male OSCC patients with buccal mucosa squamous-cell carcinoma were selected and randomly divided into ultrasound group and non-ultrasound group. Micro-CT images were obtained at 0.5 h, 1 h, 2 h, and 4 h after staining with 3% Lugol's iodine, and CNR was used to quantitative analyze the image clarity between tumor and normal tissue. Results: When Cal-27 was exposed to ultrasound for 5 min and 10 min, the AOD of 1% and 3% Lugol's iodine was higher than that of the control group (P<0.05). The value of micro-CT imaging of mouse tongue under ultrasound was higher than that of control group (P<0.05). The OSCC specimen results showed that the tumor and normal tissue boundaries were visible on micro-CT imaging with 3% Lugol's iodine staining for 2 h, while the dividing line was visible on HE sections. Conclusion: Ultrasound-assisted Lugol's iodine accelerates the infiltration of Cal-27, while ultrasound-assisted Lugol's iodine-enhanced micro-CT imaging provides some clinical guidance for intraoperative margin assessment of OSCC specimens.

Key words: ultrasound, micro-CT, Lugol's iodine, oral squamous cell carcinoma, surgical margin

NIU Yanhong, XIA Chengwan, ZHANG Qian, MA Guanyu, WANG Yuxin, HU Qingang, PU Yumei. Feasibility Study on Intraoperative Lugol's Iodine Enhanced Micro-CT Imaging Accelerated by Ultrasound for Specimen of Oral Squamous Cell Carcinoma[J]. Journal of Oral Science Research, 2023, 39(11): 982-987.

References

[1] Cristaldi M, Mauceri R, Di Fede O, et al. Salivary biomarkers for oral squamous cell carcinoma diagnosis and follow-up: Current status and perspectives[J]. Front Physiol, 2019, 10:1476.
[2] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3):209-249.
[3] Tu IW, Shannon NB, Thankappan K, et al. Risk stratification in oral cancer: A novel approach[J]. Front Oncol, 2022, 12:836803.
[4] van Houten V, Leemans C, Kummer J, et al. Molecular diagnosis of surgical margins and local recurrence in head and neck cancer patients: a prospective study[J]. Clin Cancer Res, 2004, 10(11):3614-3620.
[5] Sunkara PR, Graff JT, Cramer JD. Association of surgical margin distance with survival in patients with resected head and neck squamous cell carcinoma: A secondary analysis of a randomized clinical trial[J]. JAMA Otolaryngol Head Neck Surg, 2023 , 149(4):317-326.
[6] Coutu B, Ryan E, Christensen D, et al. Positive margins matter regardless of subsequent resection findings[J]. Oral Oncol, 2022, 128:105850.
[7] Xia CW, Gan RL, Pan JR, et al. Lugol's iodine-enhanced micro-CT: A potential 3-D imaging method for detecting tongue squamous cell carcinoma specimens in surgery[J]. Front Oncol, 2020, 10:550171.
[8] Callahan S, Crowe-Riddell JM, Nagesan RS, et al. A guide for optimal iodine staining and high-through put diceCT scanning in snakes[J]. Ecol Evol, 2021 , 11(17):11587-11603.
[9] Heimel P, Swiadek NV, Slezak P, et al. Iodine-enhanced micro-CT imaging of soft tissue on the example of peripheral nerve regeneration[J]. Contrast Media Mol Imaging, 2019, 2019:7483745.
[10] Llambrich S, Wouters J, Himmelreich U, et al. ViceCT and whiceCT for simultaneous high-resolution visualization of craniofacial, brain and ventricular anatomy from micro-computed tomography[J]. Sci Rep, 2020, 10(1):18772.
[11] Ma Y, Chen X, Zhu W, et al. Speckle noise reduction in optical coherence tomography images based on edge-sensitive cGAN[J]. Biomed Opt Express, 2018, 9(11): 5129-5146.
[12] Liu K, Shen C, Chen X. Expression of androgen receptor in coronary artery in the cases of sudden coronary death[J]. Int J Clin Exp Pathol, 2015, 8(4):3742-3747.
[13] Vahdani N, Moudi E, Ghobadi F, et al. Evaluation of the metal artifact caused by dental implants in cone beam computed tomography images[J]. Maedica (Bucur), 2020,15(2):224-229.
[14] Slooter MD, Handgraaf HJM, Boonstra MC, et al. Detecting tumour-positive resection margins after oral cancer surgery by spraying a fluorescent tracer activated by gamma-glutamyltranspeptidase[J]. Oral Oncol, 2018, 78:1-7.
[15] Manhoobi IP, Bodilsen A, Nijkamp J, et al.Diagnostic accuracy of radiography, digital breast tomosynthesis, micro-CT and ultrasound for margin assessment during breast surgery: A systematic review and meta-analysis[J]. Acad Radiol, 2022, 29(10):1560-1572.
[16] DiCorpo D, Tiwari A, Tang R, et al.The role of Micro-CT in imaging breast cancer specimens[J]. Breast Cancer Res Treat, 2020, 180(2):343-357.
[17] Yoshida M, Cesmecioglu E, Firat C, et al. Pathological evaluation of rectal cancer specimens using micro-computed tomography[J]. Diagnostics (Basel), 2022, 12(4):984.
[18] Apps JR, Hutchinson JC, Arthurs OJ, et al. Imaging invasion: Micro-CT imaging of adamantinomatous craniopharyngioma highlights cell type specific spatial relationships of tissue invasion[J]. Acta Neuropathol Commun,2016, 4(1): 57.
[19] Heimel P, Swiadek NV, Slezak P, et al. Iodine-enhanced micro-CT imaging of soft tissue on the example of peripheral nerve regeneration[J]. Contrast Media Mol Imaging, 2019, 2019:7483745.
[20] Datta S, Mishra A, Chaturvedi P, et al. Frozen section is not cost beneficial for the assessment of margins in oral cancer[J]. Indian J Cancer, 2019, 56(1):19-23.
[21] Nentwig K, Unterhuber T, Wolff KD, et al.The impact of intraoperative frozen section analysis on final resection margin status, recurrence, and patient outcome with oral squamous cell carcinoma[J]. Clin Oral Investig, 2021, 25(12):6769-6777.
[22] Chang KW, Noh SH, Park JY, et al. Retrospective study on accuracy of intraoperative frozen section biopsy in spinal tumors[J]. World Neurosurg, 2019, 129:e152-e157.
[23] Hegde P, Gunishetty V, Shetty V, et al. Intraoperative evaluation of the resected bone margin in mandibular cancers using a trephine drill and frozen section analysis[J]. Int J Oral Maxillofac Surg, 2023, 52(4):409-412.
[24] Long SM, Mclean T, Valero Mayor C, et al. Use of intraoperative frozen section to assess final tumor margin status in patients undergoing surgery for oral cavity squamous cell carcinoma[J]. JAMA Otolaryngol Head Neck Surg, 2022, 148(10):911-917.
[25] Kubik MW, Sridharan S, Varvares MA, et al. Intraoperative margin assessment in head and neck cancer: A case of misuse and abuse?[J]. Head Neck Pathol,2020, 14(2):291-302.
[26] Zaw Thin M, Moore C, Snoeks T, et al. Micro-CT acquisition and image processing to track and characterize pulmonary nodules in mice[J]. Nat Protoc, 2023, 18(3):990-1015.
[27] Yang C, Li Y, Du M, et al. Recent advances in ultrasound-triggered therapy[J]. J Drug Target, 2019, 27(1):33-50.
[28] Yang C, Li Y, Du M, et al. Recent advances in ultrasound-triggered therapy[J]. J Drug Target, 2019, 27(1):33-50.
[29] Humphrey VF. Ultrasound and matter--physical interactions[J]. Prog Biophys Mol Biol, 2007, 93(1-3):195-211.
[30] Komarov S, Yamamoto T, Sun J. Fabrication of Al-Bi frozen emulsion alloys due to high-intense ultrasound irradiation[J]. J Alloys Compd, 2021, 859: 158231.
[31] Lin C, Chen YZ, Wu B, et al. Advances and prospects of ultrasound targeted drug delivery systems using biomaterial-modified micro/nanobubbles for tumor therapy[J]. Curr Med Chem, 2022, 29(30):5062-5075.
[32] Pinto R, Matula J, Gomez-Lazaro M, et al. High-resolution micro-CT for 3D infarct characterization and segmentation in mice stroke models[J]. Sci Rep, 2022, 12(1):17471.