Department of Clinical Radiology, University Hospital Muenster, Albert-Schweitzer-Str. 33, D-48149 Münster, Germany.
Radiology. 2010 Jun;255(3):781-9. doi: 10.1148/radiol.10090832.
To evaluate a susceptibility-corrected multiecho magnetic resonance (MR) relaxometry technique for an accurate and robust determination of DeltaR2* as a noninvasive surrogate parameter of the perfused tumor blood volume.
All experiments were approved by the institutional animal care committee. In a glass tube phantom with different superparamagnetic iron oxide (SPIO) particle concentrations and at tumor mice xenografts with DU-4475, HT-1080, and MDA-MB-435 tumors (n = 15 total, n = 5 per model) with different degrees of neovascularization after injection of different ultrasmall SPIO (USPIO) doses changes of the transverse relaxation rate (DeltaR2*) were determined by using a fixed echo time (TE) of 22 msec and a susceptibility-corrected multigradient-echo technique. The mean DeltaR2* value and the vascular volume fraction (VVF) of each tumor was determined and compared with independent in vivo fluorescent tumor perfusion measurements and histologic analysis helped determine microvessel density (MVD). Statistical differences were tested by using analysis of variance and linear correlations.
For the phantom study, DeltaR2* maps calculated with a fixed TE of 22 msec showed a higher standard deviation of the noise index compared with the susceptibility-corrected multiecho technique. For the xenograft model, mean tumor DeltaR2* values (+/- standard error of the mean) showed significant differences between the various tumors (eg, DU-4475: 12.3 sec(-1) +/- 2.67, HT-1080: 36.47 sec(-1) +/- 5.84, and MDA-MB-435: 64.01 sec(-1) +/- 8.87 at 80 mumol of iron per kilogram; P < .05). DeltaR2* values increased dose dependently and in a linear fashion, resulting in reproducibly stable VVF measurements. Fluorescent tumor perfusion measurements and MVD counts corroborated the MR results.
Susceptibility-corrected multiecho MR relaxometry allows a highly accurate and robust determination of DeltaR2* and VVF with an excellent dynamic range for tumor characterization at clinically relevant doses of USPIO.
评估一种校正磁化率的多回波磁共振(MR)弛豫度技术,以便准确、稳健地测定 DeltaR2*,作为一种无创的肿瘤血流灌注量替代参数。
所有实验均获得机构动物护理委员会批准。在玻璃管模型中,对超顺磁性氧化铁(SPIO)粒子浓度不同的模型,以及在注射不同超小超顺磁性氧化铁(USPIO)剂量后,有不同程度新生血管形成的 DU-4475、HT-1080 和 MDA-MB-435 肿瘤的荷瘤鼠中(共 15 只,每种模型 5 只),采用固定回波时间(TE)为 22 毫秒和校正磁化率的多梯度回波技术,测定横向弛豫率(DeltaR2*)的变化。测定每个肿瘤的平均 DeltaR2*值和血管体积分数(VVF),并与独立的体内荧光肿瘤灌注测量和组织学分析确定微血管密度(MVD)进行比较。采用方差分析和线性相关性检验进行统计学差异检验。
在模型研究中,采用固定 TE 为 22 毫秒计算的 DeltaR2图,其噪声指数的标准偏差高于校正磁化率的多回波技术。在荷瘤鼠模型中,各种肿瘤的平均肿瘤 DeltaR2值(均数 +/- 标准误)差异有统计学意义(例如,DU-4475:12.3 秒(-1) +/- 2.67,HT-1080:36.47 秒(-1) +/- 5.84,MDA-MB-435:64.01 秒(-1) +/- 8.87,在 80 微摩尔/千克的铁剂量下;P<.05)。DeltaR2*值呈剂量依赖性和线性增加,导致 VVF 测量结果稳定。荧光肿瘤灌注测量和 MVD 计数与 MR 结果一致。
校正磁化率的多回波 MR 弛豫度技术可在临床上相关的 USPIO 剂量下,对肿瘤进行高精确、稳健的 DeltaR2*和 VVF 测定,并具有出色的动态范围。