Neuroplasticity and Neural Activity Lab, Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal.
Radiology Department, Champalimaud Centre for the Unknown, Lisbon, Portugal.
Cancer Res. 2019 May 1;79(9):2435-2444. doi: 10.1158/0008-5472.CAN-18-3682. Epub 2019 Mar 20.
Noninvasive characterization of lymph node involvement in cancer is an enduring onerous challenge. In rectal cancer, pathologic lymph node status constitutes the most important determinant of local recurrence and overall survival, and patients with involved lymph nodes may benefit from preoperative chemo and/or radiotherapy. However, knowledge of lymph node status before surgery is currently hampered by limited imaging accuracy. Here, we introduce Susceptibility-Perturbation MRI (SPI) as a novel source of contrast to map malignant infiltration into mesorectal lymph nodes. SPI involves multigradient echo (MGE) signal decays presenting a nonmonoexponential nature, which we show is sensitive to the underlying microstructure via susceptibility perturbations. Using numerical simulations, we predicted that the large cell morphology and the high cellularity of tumor within affected mesorectal lymph nodes would induce signature SPI decays. We validated this prediction in mesorectal lymph nodes excised from total mesorectal excision specimens of patients with rectal cancer using ultrahigh field (16.4 T) MRI. SPI signals distinguished benign from malignant nodal tissue, both qualitatively and quantitatively, and our histologic analyses confirmed cellularity and cell size were the likely underlying sources for the differences observed. SPI was then adapted to a clinical 1.5 T scanner, added to patients' staging protocol, and compared with conventional assessment by two expert radiologists. Nonmonoexponential decays, similar to those observed in the study, were demonstrated, and SPI classified lymph nodes more accurately than standard high-resolution T-weighted imaging assessment. These findings suggest this simple, yet highly informative, method can improve rectal cancer patient selection for neoadjuvant therapy. SIGNIFICANCE: These findings introduce an MRI methodology tailored to detect magnetic susceptibility perturbations induced by subtle alterations in tissue microstructure.
非侵入性的癌症淋巴结受累评估一直是一项艰巨的挑战。在直肠癌中，病理淋巴结状态是局部复发和总生存的最重要决定因素，淋巴结受累的患者可能受益于术前化疗和/或放疗。然而，目前手术前的淋巴结状态知识受到成像准确性的限制。在这里，我们引入了磁化率-扰动量 MRI（SPI）作为一种新的对比方法，用于对直肠系膜淋巴结中的恶性浸润进行成像。SPI 涉及多梯度回波（MGE）信号衰减，表现出非单指数性质，我们通过磁化率扰动量显示其对潜在的微观结构敏感。通过数值模拟，我们预测肿瘤在受影响的直肠系膜淋巴结中的大细胞形态和高细胞密度会引起 SPI 衰减的特征。我们使用超高场（16.4T）MRI 验证了这一预测，对来自接受直肠癌全直肠系膜切除术的患者的直肠系膜淋巴结进行了验证。SPI 信号定性和定量地区分了良性和恶性的淋巴结组织，我们的组织学分析证实细胞密度和细胞大小是观察到的差异的可能来源。然后将 SPI 适应于临床 1.5T 扫描仪，添加到患者的分期方案中，并与两位专家放射科医生的常规评估进行比较。与研究中观察到的相似，观察到了非单指数衰减，并且 SPI 比标准高分辨率 T 加权成像评估更准确地分类淋巴结。这些发现表明，这种简单但信息丰富的方法可以改善直肠癌患者对新辅助治疗的选择。意义：这些发现介绍了一种针对检测组织微观结构细微变化引起的磁化率扰动的 MRI 方法。
