Netto Joao Prola, Schwartz Daniel, Varallyay Csanad, Fu Rongwei, Hamilton Bronwyn, Neuwelt Edward A
Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Department of Neuroradiology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Fluids Barriers CNS. 2016 Dec 20;13(1):23. doi: 10.1186/s12987-016-0047-9.
Neovascularization, a distinguishing trait of high-grade glioma, is a target for anti-angiogenic treatment with bevacizumab (BEV). This study sought to use ferumoxytol-based dynamic susceptibility contrast magnetic resonance imaging (MRI) to clarify perfusion and relative blood volume (rCBV) changes in glioma treated with BEV and to determine potential impact on clinical management.
16 high grade glioma patients who received BEV following post-chemoradiation radiographic or clinical progression were included. Ferumoxytol-based MRI perfusion measurements were taken before and after BEV. Lesions were defined at each timepoint by gadolinium-based contrast agent (GBCA)-enhancing area. Lesion volume and rCBV were compared pre and post-BEV in the lesion and rCBV "hot spot" (mean of the highest rCBV in a 1.08 cm area in the enhancing volume), as well as hypoperfused and hyperperfused subvolumes within the GBCA-enhancing lesion.
GBCA-enhancing lesion volumes decreased 39% (P = 0.01) after BEV. Mean rCBV in post-BEV GBCA-enhancing area did not decrease significantly (P = 0.227) but significantly decreased in the hot spot (P = 0.046). Mean and hot spot rCBV decreased (P = 0.039 and 0.007) when post-BEV rCBV was calculated over the pre-BEV GBCA-enhancing area. Hypoperfused pixel count increased from 24% to 38 (P = 0.007) and hyperperfused decreased from 39 to 28% (P = 0.017). Mean rCBV decreased in 7/16 (44%) patients from >1.75 to <1.75, the cutoff for pseudoprogression diagnosis.
Decreased perfusion after BEV significantly alters rCBV measurements when using ferumoxytol. BEV treatment response hinders efforts to differentiate true progression from pseudoprogression using blood volume measurements in malignant glioma, potentially impacting patient diagnosis and management.
新生血管形成是高级别胶质瘤的一个显著特征，是贝伐单抗（BEV）抗血管生成治疗的靶点。本研究旨在利用基于 ferumoxytol 的动态磁敏感对比磁共振成像（MRI）来阐明接受 BEV 治疗的胶质瘤的灌注和相对血容量（rCBV）变化，并确定其对临床管理的潜在影响。
纳入 16 例在放化疗后影像学或临床进展后接受 BEV 治疗的高级别胶质瘤患者。在 BEV 治疗前后进行基于 ferumoxytol 的 MRI 灌注测量。在每个时间点，通过钆基造影剂（GBCA）增强区域定义病变。比较 BEV 治疗前后病变及 rCBV“热点”（增强体积中 1.08 cm 区域内最高 rCBV 的平均值）的病变体积和 rCBV，以及 GBCA 增强病变内的低灌注和高灌注子体积。
BEV 治疗后，GBCA 增强的病变体积减少了 39%（P = 0.01）。BEV 治疗后 GBCA 增强区域的平均 rCBV 没有显著下降（P = 0.227），但在热点区域显著下降（P = 0.046）。当在 BEV 治疗前的 GBCA 增强区域计算 BEV 治疗后的 rCBV 时，平均和热点 rCBV 下降（P = 0.039 和 0.007）。低灌注像素计数从 24%增加到 38%（P = 0.007），高灌注像素计数从 39%下降到 28%（P = 0.017）。16 例患者中有 7 例（44%）的平均 rCBV 从>1.75 降至<1.75，这是假性进展诊断的临界值。
BEV 治疗后灌注减少在使用 ferumoxytol 时会显著改变 rCBV 测量值。BEV 治疗反应阻碍了在恶性胶质瘤中利用血容量测量来区分真正进展与假性进展的努力，可能影响患者的诊断和管理。
