3.0 T单体素磁共振波谱成像离体及在体检测2-羟基戊二酸效能初探

Efficiency of 2-hydroxyglutarate quantification by long-echo proton magnetic resonance spectroscopy at 3.0 T in vitro and in vivo

目的通过氢质子磁共振波谱技术(proton magnetic resonance spectroscopy,^1H-MRS)离体及在体检测异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)突变后产生的代谢物2-羟基戊二酸(2-hydroxyglutarate,2HG),探索临床3.0 T核磁共振机应用长回波时间(echo time,TE)单体素不对称自旋回波点解析波谱(point-resolved spectroscopy,PRESS)序列检测2HG的效能。材料与方法配制包含不同代谢物的两组体外水模,于T2WI液体衰减反转恢复序列(fluid attenuated inversion recovery,FLAIR)像上对各水模中心位置进行MRS感兴趣定位,采用长TE PRESS序列进行MRS成像。使用相同扫描参数,结合患者T1WI、T1WI增强图像,对拟诊为低级别胶质瘤的4例患者进行脑MRS成像,以术后基因检测获得的IDH基因突变状态作为金标准。水模及在体波谱中代谢物的绝对浓度值均通过LC model软件拟合后获得。结果体外水模扫描结果显示,当2HG配制浓度在2~16 mmol/L时,均能有效检测出2HG,相比2HG配制的真实浓度值,通过LC model计算得到的2HG绝对浓度值降低,而水模中2HG/谷氨酸(glutamate,Glu)的浓度比值与实际比值接近。在体扫描结果显示,在符合入组标准的3例患者中,2例IDH突变型胶质瘤患者均有效检测出2HG蓄积,1例IDH野生型胶质瘤未检测出2HG蓄积。结论水模扫描结果表明,临床环境中通过长TE PRESS序列检测2HG浓度水平时,低浓度2HG会被掩盖,从而增加假阴性的结果。而2HG/Glu的比值与实际比值较为接近,提示用比值替代绝对浓度可能更具准确性。结合在体扫描结果表明,临床环境中,在常规胶质瘤影像序列中加入长TE PRESS序列检测2HG蓄积水平,从而间接预测IDH基因突变状态具有较好的可行性,这对于胶质瘤分子分型的术前无创诊断、指导治疗策略及预后评估具有重要意义。

Objective:Mutated isocitrate dehydrogenase(IDH)produce high accumulation levels of 2-hydroxyglutarate(2 HG)that can be quantitatively detected by proton magnetic resonance spectroscopy(^1H-MRS).Through in vitro and in vivo studies,the purpose of our study was to explore the efficacy of using long-echo(TE)point-resolved spectroscopy(PRESS)MRS to detect 2 HG at 3.0 T in clinical setting.Materials and Methods:Two phantoms were set up,the first is a spherical phantom(diameter of about 6 cm plastic ball),which containing a range of known concentrations of 2 HG 9 mmol/L,Glutamate(Glu)12.5 mmol/L,Glutamine(Gln)12.5 mmol/L,γ-Aminobutyric Acid(GABA)2.0 mmol/L,N-acetylaspartate(NAA)12.5 mmol/L,Creatine(Cr)10.0 mmol/L,Choline(Cho)3.0 mmol/L;The second includes six cylindrical gradient phantoms(both 60 mL plastic test tubes),and Glu 10 mmol/L,Cr 10 mmol/L,and 2 HG 0.5,1,2,4,8,16 mmol/L,respectively.Point-resolved spectroscopy(PRESS)sequence with long echo time(TE=97 ms,TE1=26 ms,TE2=71 ms)MRS was used to analyze for all the set phantoms.In addition,combined with T1 WI and T1 WI enhanced images,long TE PRESS MRS was performed on 4 subjects with suspected diagnosis of low-grade glioma in our study.IDH mutation status obtained by postoperative genetic testing was taken as the gold standard.The absolute concentration values of metabolites were acquired by LC model software fitting.Results:Phantoms results showed that 2 HG could be detected effectively when the concentration of 2 HG was 2-16 mmol/L.Compared with the real concentration of 2 HG,the absolute concentration of 2 HG obtained by LC model software was lower,while the concentration ratio of 2 HG/Glu was close to the actual ratio.Three subjects were subsequently diagnosed histologically as gliomas,of which 2 were IDH mutant gliomas and 1 was IDH wild-type glioma.By long TE PRESS,the accumulation of 2 HG was detected effectively in IDH mutant glioma,while there is no accumulation of 2 HG in IDH wild-type glioma.Conclusions:The results of phantoms suggest that 2 HG at low concentration can be masked and thus increase the false negative result.However,the ratio of 2 HG/Glu is closer to the actual ratio,indicating that it may be more accurate to replace the absolute concentration value with the ratio.Combined with the results of scanning in vivo shows that it was feasible to use long TE PRESS sequence in the conventional glioma imaging protocol to detect 2 HG accumulation and indirectly predict IDH mutation status.It is of great significance for the preoperative non-invasive diagnosis,guiding treatment strategy and prognosis evaluation of glioma.