Characterization of serial hyperpolarized 13C metabolic imaging in patients with glioma.,NeuroImage: Clinical

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Characterization of serial hyperpolarized 13C metabolic imaging in patients with glioma.
NeuroImage: Clinical ( IF 3.4 ) Pub Date : 2020-06-24 , DOI: 10.1016/j.nicl.2020.102323
Adam W Autry ₁ , Jeremy W Gordon ₁ , Hsin-Yu Chen ₁ , Marisa LaFontaine ₁ , Robert Bok ₁ , Mark Van Criekinge ₁ , James B Slater ₁ , Lucas Carvajal ₁ , Javier E Villanueva-Meyer ₁ , Susan M Chang ₂ , Jennifer L Clarke ₂ , Janine M Lupo ₁ , Duan Xu ₁ , Peder E Z Larson ₁ , Daniel B Vigneron ₃ , Yan Li ₁

Affiliation

Background

Hyperpolarized carbon-13 (HP-¹³C) MRI is a non-invasive imaging technique for probing brain metabolism, which may improve clinical cancer surveillance. This work aimed to characterize the consistency of serial HP-¹³C imaging in patients undergoing treatment for brain tumors and determine whether there is evidence of aberrant metabolism in the tumor lesion compared to normal-appearing tissue.

Methods

Serial dynamic HP [1-¹³C]pyruvate MRI was performed on 3 healthy volunteers (6 total examinations) and 5 patients (21 total examinations) with diffuse infiltrating glioma during their course of treatment, using a frequency-selective echo-planar imaging (EPI) sequence. HP-¹³C imaging at routine clinical timepoints overlapped treatment, including radiotherapy (RT), temozolomide (TMZ) chemotherapy, and anti-angiogenic/investigational agents. Apparent rate constants for [1-¹³C]pyruvate conversion to [1-¹³C]lactate (k_PL) and [¹³C]bicarbonate (k_PB) were simultaneously quantified based on an inputless kinetic model within normal-appearing white matter (NAWM) and anatomic lesions defined from ¹H MRI. The inter/intra-subject consistency of k_PL-NAWM and k_PB-NAWM was measured in terms of the coefficient of variation (CV).

Results

When excluding scans following anti-angiogenic therapy, patient values of k_PL-NAWM and k_PB-NAWM were 0.020 s⁻¹ ± 23.8% and 0.0058 s⁻¹ ± 27.7% (mean ± CV) across 17 HP-¹³C MRIs, with intra-patient serial k_PL-NAWM/k_PB-NAWM CVs ranging 6.8–16.6%/10.6–40.7%. In 4/5 patients, these values (0.018 s⁻¹ ± 13.4% and 0.0058 s⁻¹ ± 24.4%; n = 13) were more similar to those from healthy volunteers (0.018 s⁻¹ ± 5.0% and 0.0043 s⁻¹ ± 12.6%; n = 6) (mean ± CV). The anti-angiogenic agent bevacizumab was associated with global elevations in apparent rate constants, with maximum k_PL-NAWM in 2 patients reaching 0.047 ± 0.001 and 0.047 ± 0.003 s⁻¹ (±model error). In 3 patients with progressive disease, anatomic lesions showed elevated k_PL relative to k_PL-NAWM of 0.024 ± 0.001 s⁻¹ (±model error) in the absence of gadolinium enhancement, and 0.032 ± 0.008, 0.040 ± 0.003 and 0.041 ± 0.009 s⁻¹ with gadolinium enhancement. The lesion k_PB in patients was reduced to unquantifiable values compared to k_PB-NAWM.

Conclusion

Serial measures of HP [1-¹³C]pyruvate metabolism displayed consistency in the NAWM of healthy volunteers and patients. Both k_PL and k_PB were globally elevated following bevacizumab treatment, while progressive disease demonstrated elevated k_PL in gadolinium-enhancing and non-enhancing lesions. Larger prospective studies with homogeneous patient populations are planned to evaluate metabolic changes following treatment.

中文翻译：

胶质瘤患者的连续超极化13 C代谢成像的表征。

背景

超极化碳13（HP- ¹³ C）MRI是探测脑部新陈代谢的一种非侵入性成像技术，可以改善临床癌症的监测。这项工作旨在表征正在接受脑瘤治疗的患者中连续HP- ¹³ C成像的一致性，并确定与正常出现的组织相比，肿瘤病变中是否存在异常代谢的证据。

方法

串行动态HP [1- ¹³ C]丙酮酸MRI是3名健康志愿者（6个总考试）和5例（21个总检查）弥漫浸润神经胶质瘤其治疗过程期间执行，使用频率选择性回波平面成像（ EPI）序列。常规临床时间点的HP- ¹³ C成像与治疗重叠，包括放疗（RT），替莫唑胺（TMZ）化学疗法和抗血管生成/研究药物。[1- ¹³ C]丙酮酸盐转化为[1-1 ¹³ C]乳酸（k _PL）和[ ¹³ C]碳酸氢盐（k _PB）的表观速率常数）同时根据正常出现的白质（NAWM）和¹ H MRI定义的解剖病变内的无输入动力学模型进行定量。用变异系数（CV）测量k _PL-NAWM和k _PB-NAWM的受试者间/受试者内一致性。

结果

当排除抗血管生成治疗后的扫描结果时，在17项HP- ¹³ C MRI中，k _PL-NAWM和k _PB-NAWM的患者值为0.020 s ^-1 ±23.8％和0.0058 s ^-1 ±27.7％（平均值±CV），患者内串行k _PL-NAWM / k _PB-NAWM CV范围为6.8–16.6％/ 10.6–40.7％。在4/5位患者中，这些值（0.018 s ^-1 ±13.4％和0.0058 s ^-1 ±24.4％；n = 13）与健康志愿者的值更相似（0.018 s ^-1 ±5.0％和0.0043 s ^-1 ±12.6％; n = 6）（平均值±CV）。抗血管生成剂贝伐单抗与表观速率常数的整体升高有关，其中2名患者的最大k _PL-NAWM达到0.047±0.001和0.047±0.003 s ^-1（±模型误差）。在3例进行性疾病，解剖病灶升高ķ _PL相对于ķ _PL-NAWM的0.024±0.001小号^-1（±模型误差）在不存在钆增强的，和0.032±0.008，0.040±0.003 0.041和0.009± − ^-1增强。与k _PB-NAWM相比，患者的病变k _PB降低至无法量化的值。