Cancer Biophysics laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus.
Department of Diagnostic Physics, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
Neuroimage Clin. 2018 Aug 31;20:664-673. doi: 10.1016/j.nicl.2018.08.032. eCollection 2018.
Previous studies to simulate brain tumor progression, often investigate either temporal changes in cancer cell density or the overall tissue-level growth of the tumor mass. Here, we developed a computational model to bridge these two approaches. The model incorporates the tumor biomechanical response at the tissue level and accounts for cellular events by modeling cancer cell proliferation, infiltration to surrounding tissues, and invasion to distant locations. Moreover, acquisition of high resolution human data from anatomical magnetic resonance imaging, diffusion tensor imaging and perfusion imaging was employed within the simulations towards a realistic and patient specific model. The model predicted the intratumoral mechanical stresses to range from 20 to 34 kPa, which caused an up to 4.5 mm displacement to the adjacent healthy tissue. Furthermore, the model predicted plausible cancer cell invasion patterns within the brain along the white matter fiber tracts. Finally, by varying the tumor vascular density and its invasive outer ring thickness, our model showed the potential of these parameters for guiding the timing (83-90 days) of cancer cell distant invasion as well as the number (0-2 sites) and location (temportal and/or parietal lobe) of the invasion sites.
先前的研究为模拟脑肿瘤的进展,通常会调查癌细胞密度的时间变化或肿瘤质量的整体组织水平增长。在这里,我们开发了一个计算模型来连接这两种方法。该模型在组织水平上纳入了肿瘤的生物力学反应,并通过建模癌细胞增殖、浸润周围组织以及入侵远处部位来考虑细胞事件。此外,还在模拟中采用了从解剖磁共振成像、弥散张量成像和灌注成像获得的高分辨率人体数据,以实现更真实和个体化的模型。该模型预测肿瘤内的机械应力范围为 20 至 34kPa,这会导致相邻健康组织发生高达 4.5mm 的位移。此外,该模型还预测了大脑中沿着白质纤维束的可能的癌细胞入侵模式。最后,通过改变肿瘤的血管密度和其侵袭性外环线厚度,我们的模型表明这些参数具有指导癌细胞远处侵袭时间(83-90 天)以及侵袭部位数量(0-2 个部位)和位置(颞叶和/或顶叶)的潜力。