From the Centre for Imaging Sciences (R.A.L., J.H.N., Y.W., S.C., K.F.H., H.L., D.J.M., G.J.M.P., J.C.W.) and Division of Cancer Sciences (J.I., C.M.L.W., N.W.C., J.P.B.O.), University of Manchester, Manchester, England; Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, England (Y.J., J.K.R.B., S.P.R.); Department of Pathology, Central Manchester University Hospitals NHS Foundation Trust, Manchester, England (G.N.B.); Department of Histology, CRUK Manchester Institute, Manchester, England (G.A.); Tumour Biology Team, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, England (A.R.R.); Department of Urology, Salford Royal Hospitals NHS Foundation Trust, Salford, England (S.M., N.W.C.); Bioxydyn Ltd, Manchester, England (G.J.M.P., J.C.W.); and Department of Radiology, The Christie NHS Foundation Trust, Manchester, England (J.P.B.O.).
Radiology. 2018 Sep;288(3):739-747. doi: 10.1148/radiol.2018171531. Epub 2018 Jun 5.
Purpose To cross-validate T1-weighted oxygen-enhanced (OE) MRI measurements of tumor hypoxia with intrinsic susceptibility MRI measurements and to demonstrate the feasibility of translation of the technique for patients. Materials and Methods Preclinical studies in nine 786-0-R renal cell carcinoma (RCC) xenografts and prospective clinical studies in eight patients with RCC were performed. Longitudinal relaxation rate changes (∆R1) after 100% oxygen inhalation were quantified, reflecting the paramagnetic effect on tissue protons because of the presence of molecular oxygen. Native transverse relaxation rate (R2*) and oxygen-induced R2* change (∆R2*) were measured, reflecting presence of deoxygenated hemoglobin molecules. Median and voxel-wise values of ∆R1 were compared with values of R2* and ∆R2*. Tumor regions with dynamic contrast agent-enhanced MRI perfusion, refractory to signal change at OE MRI (referred to as perfused Oxy-R), were distinguished from perfused oxygen-enhancing (perfused Oxy-E) and nonperfused regions. R2* and ∆R2* values in each tumor subregion were compared by using one-way analysis of variance. Results Tumor-wise and voxel-wise ∆R1 and ∆R2* comparisons did not show correlative relationships. In xenografts, parcellation analysis revealed that perfused Oxy-R regions had faster native R2* (102.4 sec vs 81.7 sec) and greater negative ∆R2* (-22.9 sec vs -5.4 sec), compared with perfused Oxy-E and nonperfused subregions (all P < .001), respectively. Similar findings were present in human tumors (P < .001). Further, perfused Oxy-R helped identify tumor hypoxia, measured at pathologic analysis, in both xenografts (P = .002) and human tumors (P = .003). Conclusion Intrinsic susceptibility biomarkers provide cross validation of the OE MRI biomarker perfused Oxy-R. Consistent relationship to pathologic analyses was found in xenografts and human tumors, demonstrating biomarker translation. Published under a CC BY 4.0 license. Online supplemental material is available for this article.
用内在磁化率 MRI 测量来验证 T1 加权氧增强 (OE) MRI 测量肿瘤缺氧的准确性，并证明该技术在患者中转化应用的可行性。
对 9 例 786-0-R 肾细胞癌 (RCC) 异种移植瘤进行了临床前研究，对 8 例 RCC 患者进行了前瞻性临床研究。定量分析了吸入 100%氧气后组织质子的纵向弛豫率变化 (∆R1)，这反映了由于分子氧的存在对组织质子的顺磁效应。测量了自然横向弛豫率 (R2*) 和氧诱导的 R2变化 (∆R2)，这反映了去氧血红蛋白分子的存在。比较了 ∆R1 的中位数和体素值与 R2和 ∆R2的值。用动态对比剂增强 MRI 灌注区分具有 OE MRI 信号变化抵抗的肿瘤区域（称为灌注氧增强（perfused Oxy-E）和未灌注区域）。用单因素方差分析比较了每个肿瘤亚区的 R2和 ∆R2值。
肿瘤和体素的 ∆R1 和 ∆R2比较没有显示出相关性。在异种移植瘤中，分割分析显示，与灌注氧增强（perfused Oxy-E）和未灌注亚区相比，灌注氧增强抵抗（perfused Oxy-R）区域具有更快的自然 R2（102.4 sec 比 81.7 sec）和更大的负 ∆R2*（-22.9 sec 比-5.4 sec）（均 P <.001）。在人类肿瘤中也存在类似的发现（P <.001）。此外，在异种移植瘤（P =.002）和人类肿瘤（P =.003）中，灌注氧增强抵抗（perfused Oxy-R）有助于确定病理分析中的肿瘤缺氧。
内在磁化率生物标志物对 OE MRI 生物标志物灌注氧增强（perfused Oxy-R）进行了交叉验证。在异种移植瘤和人类肿瘤中均发现与病理分析有一致的关系，证明了生物标志物的转化。
在知识共享署名 4.0 国际许可协议下发布此内容。本文提供了在线补充材料。
