Berrington Adam, Voets Natalie L, Larkin Sarah J, de Pennington Nick, Mccullagh James, Stacey Richard, Schofield Christopher J, Jezzard Peter, Clare Stuart, Cadoux-Hudson Tom, Plaha Puneet, Ansorge Olaf, Emir Uzay E
FMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
NMR Biomed. 2018 Mar;31(3). doi: 10.1002/nbm.3886. Epub 2018 Jan 5.
Abnormally high levels of the 'oncometabolite' 2-hydroxyglutarate (2-HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. In vivo measurement of 2-HG in patients, using magnetic resonance spectroscopy (MRS), has largely been carried out at 3 T, yet signal overlap continues to pose a challenge for 2-HG detection. To combat this, several groups have proposed MRS methods at ultra-high field (≥7 T) where theoretical increases in signal-to-noise ratio and spectral resolution could improve 2-HG detection. Long echo time (long-TE) semi-localization by adiabatic selective refocusing (semi-LASER) (TE = 110 ms) is a promising method for improved 2-HG detection in vivo at either 3 or 7 T owing to the use of broad-band adiabatic localization. Using previously published semi-LASER methods at 3 and 7 T, this study directly compares the detectability of 2-HG in phantoms and in vivo across nine patients. Cramér-Rao lower bounds (CRLBs) of 2-HG fitting were found to be significantly lower at 7 T (6 ± 2%) relative to 3 T (15 ± 7%) (p = 0.0019), yet were larger at 7 T in an IDH wild-type patient. Although no increase in SNR was detected at 7 T (77 ± 26) relative to 3 T (77 ± 30), the detection of 2-HG was greatly enhanced through an improved spectral profile and increased resolution at 7 T. 7 T had a large effect on pairwise fitting correlations between γ-aminobutyric acid (GABA) and 2-HG (p = 0.004), and resulted in smaller coefficients. The increased sensitivity for 2-HG detection using long-TE acquisition at 7 T may allow for more rapid estimation of 2-HG (within a few spectral averages) together with other associated metabolic markers in glioma.
“肿瘤代谢物”2-羟基戊二酸（2-HG）水平异常升高在许多II级和III级胶质瘤中出现，且与异柠檬酸脱氢酶（IDH）亚型基因的突变相关。利用磁共振波谱（MRS）对患者体内的2-HG进行测量，大多是在3T下进行的，但信号重叠仍然给2-HG的检测带来挑战。为应对这一问题，多个团队提出了在超高场（≥7T）下的MRS方法，理论上信噪比和光谱分辨率的提高可以改善2-HG的检测。通过绝热选择性重聚焦实现的长回波时间（long-TE）半定位（semi-LASER）（TE = 110ms）是一种很有前景的方法，由于使用了宽带绝热定位，可在3T或7T下改善体内2-HG的检测。本研究采用先前发表的3T和7T下的semi-LASER方法，直接比较了2-HG在体模和9例患者体内的可检测性。发现2-HG拟合的克莱姆-拉奥下界（CRLB）在7T时（6±2%）显著低于3T时（15±7%）（p = 0.0019），但在一名IDH野生型患者中7T时的CRLB更大。尽管相对于3T（77±30），在7T时未检测到信噪比增加（77±26），但通过改善光谱轮廓和提高7T时的分辨率，2-HG的检测得到了极大增强。7T对γ-氨基丁酸（GABA）和2-HG之间的成对拟合相关性有很大影响（p = 0.004），并导致系数更小。在7T下使用long-TE采集提高2-HG检测的灵敏度，可能允许在胶质瘤中更快速地估计2-HG（在几个光谱平均值内）以及其他相关代谢标志物。
