K. C. C. de Bie, R. A. A. van Kollenburg, L. A. M. J. G. van Riel, M. Almasian, J. E. Freund, P. R. Bloemen, R. Zweije, J. Crezee, B. F. Coolen, G. J. Strijkers, T. M. de Reijke, J. R. Oddens, A. G. J. M. van Leeuwen, D. M. de Bruin
{"title":"CEM43 在可控体内外实验中预测病灶激光消融引起的热损伤的结果:与组织学和 MRI 的比较。","authors":"K. C. C. de Bie, R. A. A. van Kollenburg, L. A. M. J. G. van Riel, M. Almasian, J. E. Freund, P. R. Bloemen, R. Zweije, J. Crezee, B. F. Coolen, G. J. Strijkers, T. M. de Reijke, J. R. Oddens, A. G. J. M. van Leeuwen, D. M. de Bruin","doi":"10.1002/lsm.23834","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Focal laser ablation (FLA) serves as a targeted therapy for prostate cancer (PCa). Clinical studies have demonstrated significant variations in ablation volumes with consistent fiber configurations. Consequently, a prediction model is needed for the safe application of FLA in treating PCa.</p>\n </section>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>This study aimed to evaluate the reproducibility of FLA–induced temperature profiles in controlled ex vivo experiments using clinical laser treatment protocols. Additionally, it sought to examine the effectiveness of the CEM43 model in predicting the zone of irreversible damage (ZID) and to compare these findings with outcomes derived from the Arrhenius model.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Freshly excised postmortem human prostate and porcine liver specimens were used for controlled ex vivo ablation. Tissues were secured in a Perspex sample holder for precise placement of the laser fiber and thermocouples. FLA was conducted with a 1064-nm Nd:YAG laser at 3 W in continuous-wave mode for 10 min. Pre– and post–FLA 3D T1-weighted 7 T MRI scans were obtained to assess the treatment area. Whole-mount hematoxylin and eosin histological slides were prepared and digitized. On histology, the ZID was defined as the total of vaporized, carbonized, and coagulated tissue. A 2D thermal development map was created from temperature data, using bi-cubic interpolation. The cumulative equivalent thermal isoeffect dose at 43°C in minutes (CEM43) model was applied to predict the ZID, with 240 equivalent minutes (240-CEM43) used as the damage threshold. Additionally, the Arrhenius thermal model was used for comparison of CEM43 results. Predicted ZIDs were compared to MRI and histology.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>FLA treatment was performed on ex vivo human prostate samples (<i>n</i> = 2) and porcine liver specimens (<i>n</i> = 5). For human prostate tissue, FLA did not result in an identifiable ZID upon histological macroscopic examination or a lesion on MRI. Ex vivo porcine liver samples showed a clearly demarcated oval-shaped hyperintense lesion surrounding the laser fiber tip on post–FLA MRI. The MRI lesion (range 1.6–2.1 cm<sup>2</sup>) corresponded with the shape and location of the ZID on histology, but was smaller (median 1.7 vs. 3.2, <i>p</i> = 0.02). Histological examination of porcine liver samples revealed ZIDs ranging from 2.1 to 4.1 cm<sup>2</sup>, whereas 240-CEM43–predicted ZIDs ranged from 3.3 to 3.8 cm<sup>2</sup>. Although the median 240-CEM43–predicted ZID was not significantly larger than the histology ZID (3.8 vs. 3.2 cm<sup>2</sup>, <i>p</i> = 0.22), it tended to overpredict the histological results in most experiments. The median Arrhenius-predicted ZID was similar to the histological ZID (3.2 vs. 3.2 cm<sup>2</sup>, <i>p</i> = 0.56), but varied in size when comparing individual experiments (range 2.5–3.2 cm<sup>2</sup>).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>FLA on ex vivo human prostate showed no thermal damage on histopathology or MRI. Ex vivo porcine liver FLA resulted in identifiable ZID on histology and lesions on MRI. 240-CEM43 generally overestimated the ZID and had less variability compared to histology. Results from the Arrhenius model were in better agreement with the histology findings, but still did not predict the individual FLA–induced histological thermal damage. Inter-experiment ZID variability underlines the need for developing a more comprehensive predictive dosimetry model for FLA in PCa treatment.</p>\n </section>\n </div>","PeriodicalId":17961,"journal":{"name":"Lasers in Surgery and Medicine","volume":"56 8","pages":"723-733"},"PeriodicalIF":2.2000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/lsm.23834","citationCount":"0","resultStr":"{\"title\":\"Outcomes of CEM43 in Predicting Thermal Damage Induced by Focal Laser Ablation in Controlled Ex Vivo Experiments: A Comparison to Histology and MRI\",\"authors\":\"K. C. C. de Bie, R. A. A. van Kollenburg, L. A. M. J. G. van Riel, M. Almasian, J. E. Freund, P. R. Bloemen, R. Zweije, J. Crezee, B. F. Coolen, G. J. Strijkers, T. M. de Reijke, J. R. Oddens, A. G. J. M. van Leeuwen, D. M. de Bruin\",\"doi\":\"10.1002/lsm.23834\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Focal laser ablation (FLA) serves as a targeted therapy for prostate cancer (PCa). Clinical studies have demonstrated significant variations in ablation volumes with consistent fiber configurations. Consequently, a prediction model is needed for the safe application of FLA in treating PCa.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>This study aimed to evaluate the reproducibility of FLA–induced temperature profiles in controlled ex vivo experiments using clinical laser treatment protocols. 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The cumulative equivalent thermal isoeffect dose at 43°C in minutes (CEM43) model was applied to predict the ZID, with 240 equivalent minutes (240-CEM43) used as the damage threshold. Additionally, the Arrhenius thermal model was used for comparison of CEM43 results. Predicted ZIDs were compared to MRI and histology.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>FLA treatment was performed on ex vivo human prostate samples (<i>n</i> = 2) and porcine liver specimens (<i>n</i> = 5). For human prostate tissue, FLA did not result in an identifiable ZID upon histological macroscopic examination or a lesion on MRI. Ex vivo porcine liver samples showed a clearly demarcated oval-shaped hyperintense lesion surrounding the laser fiber tip on post–FLA MRI. The MRI lesion (range 1.6–2.1 cm<sup>2</sup>) corresponded with the shape and location of the ZID on histology, but was smaller (median 1.7 vs. 3.2, <i>p</i> = 0.02). Histological examination of porcine liver samples revealed ZIDs ranging from 2.1 to 4.1 cm<sup>2</sup>, whereas 240-CEM43–predicted ZIDs ranged from 3.3 to 3.8 cm<sup>2</sup>. Although the median 240-CEM43–predicted ZID was not significantly larger than the histology ZID (3.8 vs. 3.2 cm<sup>2</sup>, <i>p</i> = 0.22), it tended to overpredict the histological results in most experiments. The median Arrhenius-predicted ZID was similar to the histological ZID (3.2 vs. 3.2 cm<sup>2</sup>, <i>p</i> = 0.56), but varied in size when comparing individual experiments (range 2.5–3.2 cm<sup>2</sup>).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>FLA on ex vivo human prostate showed no thermal damage on histopathology or MRI. Ex vivo porcine liver FLA resulted in identifiable ZID on histology and lesions on MRI. 240-CEM43 generally overestimated the ZID and had less variability compared to histology. 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引用次数: 0
摘要
背景:病灶激光消融术(FLA)是一种治疗前列腺癌(PCa)的靶向疗法。临床研究表明,在光纤配置一致的情况下,消融量存在很大差异。因此,需要建立一个预测模型,以便安全应用 FLA 治疗 PCa:本研究旨在利用临床激光治疗方案,在受控体外实验中评估 FLA 诱导的温度曲线的可重复性。此外,研究还试图检验 CEM43 模型在预测不可逆损伤区(ZID)方面的有效性,并将这些结果与阿伦尼乌斯模型得出的结果进行比较:方法: 新鲜切除的死后人类前列腺和猪肝标本用于受控体外消融。组织被固定在一个 Perspex 样品支架上,以便精确放置激光光纤和热电偶。在连续波模式下使用 1064 纳米 Nd:YAG 激光器以 3 瓦功率进行 FLA,持续 10 分钟。在进行 FLA 之前和之后,均进行了 3D T1 加权 7 T MRI 扫描,以评估治疗区域。制备并数字化整张苏木精和伊红组织切片。在组织学上,ZID 被定义为汽化、碳化和凝固组织的总和。利用双立方插值法,根据温度数据绘制出二维热显影图。应用 43°C 时的累积等效热等效应剂量(CEM43)模型来预测 ZID,并以 240 等效分钟(240-CEM43)作为损伤阈值。此外,还使用阿伦尼乌斯热模型对 CEM43 结果进行比较。预测的 ZID 与核磁共振成像和组织学进行了比较:在体外人体前列腺样本(n = 2)和猪肝样本(n = 5)上进行了 FLA 处理。对于人体前列腺组织,FLA 在组织学宏观检查中未发现可识别的 ZID,在核磁共振成像中也未发现病变。活体猪肝样本在FLA后核磁共振成像上显示,激光光纤尖端周围有一个界限清晰的椭圆形高强度病变。核磁共振成像病灶(范围为 1.6-2.1 平方厘米)与组织学上 ZID 的形状和位置一致,但更小(中位数为 1.7 vs. 3.2,p = 0.02)。猪肝样本的组织学检查显示 ZID 为 2.1 至 4.1 平方厘米,而 240-CEM43 预测的 ZID 为 3.3 至 3.8 平方厘米。虽然 240-CEM43 预测的 ZID 中位数并不比组织学 ZID 大很多(3.8 对 3.2 平方厘米,p = 0.22),但在大多数实验中,它往往会高估组织学结果。Arrhenius预测的ZID中值与组织学ZID相似(3.2 vs. 3.2 cm2,p = 0.56),但在比较单个实验时,ZID的大小有所不同(范围为2.5-3.2 cm2):结论:体外人体前列腺 FLA 在组织病理学或核磁共振成像上未显示热损伤。猪肝体外 FLA 在组织病理学上导致可识别的 ZID,在核磁共振成像上导致病变。240-CEM43 通常会高估 ZID,但与组织病理学相比,其变异性较小。阿伦尼乌斯模型的结果与组织学结果的一致性较好,但仍无法预测 FLA 诱导的单个组织学热损伤。实验之间的 ZID 变异性突出表明,有必要为 PCa 治疗中的 FLA 建立一个更全面的预测剂量模型。
Outcomes of CEM43 in Predicting Thermal Damage Induced by Focal Laser Ablation in Controlled Ex Vivo Experiments: A Comparison to Histology and MRI
Background
Focal laser ablation (FLA) serves as a targeted therapy for prostate cancer (PCa). Clinical studies have demonstrated significant variations in ablation volumes with consistent fiber configurations. Consequently, a prediction model is needed for the safe application of FLA in treating PCa.
Objective
This study aimed to evaluate the reproducibility of FLA–induced temperature profiles in controlled ex vivo experiments using clinical laser treatment protocols. Additionally, it sought to examine the effectiveness of the CEM43 model in predicting the zone of irreversible damage (ZID) and to compare these findings with outcomes derived from the Arrhenius model.
Methods
Freshly excised postmortem human prostate and porcine liver specimens were used for controlled ex vivo ablation. Tissues were secured in a Perspex sample holder for precise placement of the laser fiber and thermocouples. FLA was conducted with a 1064-nm Nd:YAG laser at 3 W in continuous-wave mode for 10 min. Pre– and post–FLA 3D T1-weighted 7 T MRI scans were obtained to assess the treatment area. Whole-mount hematoxylin and eosin histological slides were prepared and digitized. On histology, the ZID was defined as the total of vaporized, carbonized, and coagulated tissue. A 2D thermal development map was created from temperature data, using bi-cubic interpolation. The cumulative equivalent thermal isoeffect dose at 43°C in minutes (CEM43) model was applied to predict the ZID, with 240 equivalent minutes (240-CEM43) used as the damage threshold. Additionally, the Arrhenius thermal model was used for comparison of CEM43 results. Predicted ZIDs were compared to MRI and histology.
Results
FLA treatment was performed on ex vivo human prostate samples (n = 2) and porcine liver specimens (n = 5). For human prostate tissue, FLA did not result in an identifiable ZID upon histological macroscopic examination or a lesion on MRI. Ex vivo porcine liver samples showed a clearly demarcated oval-shaped hyperintense lesion surrounding the laser fiber tip on post–FLA MRI. The MRI lesion (range 1.6–2.1 cm2) corresponded with the shape and location of the ZID on histology, but was smaller (median 1.7 vs. 3.2, p = 0.02). Histological examination of porcine liver samples revealed ZIDs ranging from 2.1 to 4.1 cm2, whereas 240-CEM43–predicted ZIDs ranged from 3.3 to 3.8 cm2. Although the median 240-CEM43–predicted ZID was not significantly larger than the histology ZID (3.8 vs. 3.2 cm2, p = 0.22), it tended to overpredict the histological results in most experiments. The median Arrhenius-predicted ZID was similar to the histological ZID (3.2 vs. 3.2 cm2, p = 0.56), but varied in size when comparing individual experiments (range 2.5–3.2 cm2).
Conclusion
FLA on ex vivo human prostate showed no thermal damage on histopathology or MRI. Ex vivo porcine liver FLA resulted in identifiable ZID on histology and lesions on MRI. 240-CEM43 generally overestimated the ZID and had less variability compared to histology. Results from the Arrhenius model were in better agreement with the histology findings, but still did not predict the individual FLA–induced histological thermal damage. Inter-experiment ZID variability underlines the need for developing a more comprehensive predictive dosimetry model for FLA in PCa treatment.
期刊介绍:
Lasers in Surgery and Medicine publishes the highest quality research and clinical manuscripts in areas relating to the use of lasers in medicine and biology. The journal publishes basic and clinical studies on the therapeutic and diagnostic use of lasers in all the surgical and medical specialties. Contributions regarding clinical trials, new therapeutic techniques or instrumentation, laser biophysics and bioengineering, photobiology and photochemistry, outcomes research, cost-effectiveness, and other aspects of biomedicine are welcome. Using a process of rigorous yet rapid review of submitted manuscripts, findings of high scientific and medical interest are published with a minimum delay.