Role of magnetic resonance spectroscopy for the differentiation of recurrent glioma from radiation necrosis: A systematic review and meta-analysis

PurposeDifferentiating glioma recurrence from radiation necrosis remains a great challenge. We conducted a meta-analysis to evaluate the diagnostic quality of magnetic resonance spectroscopy (MRS) in differentiating glioma recurrence from radiation necrosis.MethodsStudies about evaluation of MRS for the differential diagnosis of glioma recurrence from radiation necrosis were systematically searched in PubMed, Embase and Chinese Biomedical databases up to May 4, 2014. The data were extracted to perform heterogeneity test, threshold effect test and to calculate sensitivity (SEN), specificity (SPE) and areas under summary receiver operating characteristic curve (SROC).ResultsEighteen articles comprising a total sample size of 455 patients (447 lesions) with suspected glioma recurrence after radiotherapy, met all inclusion and exclusion criteria, and were included in our meta-analysis. Quantitative synthesis of studies showed that the pooled SEN and SPE for Cho/Cr ratio were 0.83 (95% CI: 0.77, 0.89) and 0.83 (95% CI: 0.74, 0.90). The area under the curve (AUC) under the SROC was 0.9001. The pooled SEN and SPE for Cho/NAA ratio were 0.88 (95% CI: 0.81, 0.93) and 0.86 (95% CI: 0.76, 0.93). The AUC under the SROC was 0.9185.ConclusionThis meta-analysis shows that MRS alone has moderate diagnostic performance in differentiating glioma recurrence from radiation necrosis using metabolite ratios like Cho/Cr and Cho/NAA ratio. It is strongly recommended that MRS should combine other advanced imaging technologies to improve diagnostic accuracy. This article underlines the importance of implementing multimodal imaging trials and multicentre trials in the future.     

大鼠创伤性轴索损伤后脑代谢质子磁共振波谱分析

目的 使用质子磁共振波谱(1H-MRS)研究大鼠创伤性轴索损伤(traumatic axonal injury,TAI)后组织代谢改变及其空间分布特征.方法 使大鼠头颅发生线加速和角加速运动制作TAI模型.于伤前和伤后24 h采用多体素MRS方法检测大鼠脑内多个部位的组织代谢状态,分析伤后N-乙酰门冬氨酸(NAA)/总肌酸(Cr)、NAA/胆碱类化合物(Cho)和Cho/Cr值变化及NAA/Cr值变化的空间分布特征.采用免疫组化标记β淀粉样蛋白前体蛋白(β-APP)观察轴索损伤情况.结果 与伤前相比,伤后24 h时NAA/Cr、NAA/Cho值显著下降(P<0.05).Cho/Cr值轻度升高(P>0.05);NAA/Cr值出现较大降低幅度的部位依次为脑干、海马、内囊、胼胝体和丘脑.病理学检查示这些部位出现轴索损伤.结论 TAI后脑组织出现严重代谢紊乱,以脑干、海马等部位变化最为显著.

Abstract：

Objective To investigate the brain metabolic changes and evaluate their spatial distributions after traumatic axonal injury (TAI)in rats by using proton magnetic resonance spectroscopy(1H-MRS).Methods The TAI model was made by subjecting the head of the rats to the linear and angular accelerations.The multi-voxel MRS was employed to detect the tissue metabolic state at the levels of hippocampus-caudate and pons prior to injury and at 24 hours after injury.The alterations of NAA/Cr,NAA/Cho and Cho/Cr values as well as the spatial distribution of NAA/Cr reduction were accessed. Immunohistochemical staining for β-APP was used to observe the injured axons. Results A siguificantdecrease in NAA/Cr and NAA/Cho(P<0.05)and subtle increase in Cho/Cr(P>0.05)were observed in rats at 24 hours after TAI in comparison to the pre-injury levels.Notable decrease in NAA/Cr value was observed in the areas including the brain stem,hippocampus,internal capsule,corpus callosum and thalamus,where axonal injuries were confirmed by the histological examination. Conclusion Metabolic imbalances Occur in the brains of rats with TAI.with notable changes in the brain stem and the hippocampus.     

大鼠C6胶质瘤模型的磁共振成像及1H波谱研究

目的 :评价磁共振成像及其波谱技术在大鼠胶质瘤模型研究中的应用价值。方法 :大鼠C6脑胶质瘤细胞体外培养 ,应用立体定向架将肿瘤细胞注入大鼠脑尾状核区域 ,接种后 12～ 18d分别行磁共振成像及其波谱检查 ,观察大鼠脑C6胶质瘤的磁共振成像及其波谱表现 ,并与病理学变化进行对照分析。结果 :2 4只接种大鼠脑内有 16只胶质瘤生长良好 ,磁共振成像表现为长T1、长T2 信号 ,增强后肿瘤强化明显 ,呈均匀强化或环状强化 ;磁共振波谱表现为NAA峰明显下降甚至消失 ,Cho升高为第一高峰 ,NAA/Cr比值明显下降、Cho/Cr比值明显上升 ,部分肿瘤出现乳酸峰 (Lac)或脂质峰(Lip)。病理学显示肿瘤呈浸润性生长 ,边界不清。随着肿瘤增大 ,肿瘤内部坏死明显 ,乳酸峰 (Lac)或脂质峰 (Lip)出现率增加。结论 :大鼠脑C6胶质瘤模型是一种生长稳定、较为理想的脑胶质瘤模型 ;磁共振成像 (MRI)可以准确提供胶质瘤模型的病理形态学信息 ,磁共振波谱 (MRS)则可以提供胶质瘤的代谢及生化信息。     

质子磁共振波谱在脑损伤中的研究与应用

质子磁共振波谱(H-MRS)作为一种可以检测中枢神经系统生化代谢变化的无创性新技术,可广泛用于多种神经系统疾病的评价,本文就其在外伤性脑损伤(TBI)的研究和临床应用现状及进展作一综述。     

大脑胶质瘤病磁共振成像结合磁共振波谱成像的诊断价值

目的：探讨磁共振成像（MRI）结合磁共振波谱成像（MRS）对大脑胶质瘤病的诊断价值。方法对15例经活体组织检查或手术病理证实的大脑胶质瘤病患者的临床表现及MRI平扫、增强,MRS影像学资料进行回顾性分析。MRI常规行T1WI、T2WI及FLAIR序列,采用时间飞跃法（TOF）的磁共振血管成像（MRA）,T1WI增强扫描。氢质子MRS采用单体素STEAM序列,并分析N-乙酰天门冬氨酸（NAA）、肌酸（Cr）、胆碱复合物（Cho）等物质峰值改变。结果所有病例均侵犯2个或2个以上脑叶,以颞叶、枕叶、胼胝体、基底节和丘脑等部位侵犯受累常见。病变区T1WI呈低或等低信号、T2WI呈高或混杂高信号、FLAIR上为高信号,未见明显坏死、钙化,受累区域脑组织肿胀,占位效应轻。注射钆喷酸葡胺增强扫描示10例无明显强化、3例斑片状强化、1例结节状强化、1例线状轻度强化。病变区域MRS表现为不同程度NAA降低,NAA/Cr比值降低;Cho上升,Cho/Cr和Cho/NAA的比值上升。结论 MRI结合MRS对大脑胶质瘤病的诊断及鉴别诊断具有临床价值,是目前诊断大脑胶质瘤病的首选影像学方法。     

Magnetic resonance spectroscopy in recurrent breast masses following conservative surgery and radiation therapy

Purpose

The purpose of our study was to assess the value of functional magnetic resonance spectroscopy (1H MRS) in evaluating patients with recurrent cancer breast after breast conservative therapy (BCT) and radiation therapy by the presence of the choline-containing compounds (Cho) as a marker of malignancy.

Patients and methods

Twenty-six patients were included in the study all the patients were subjected to previous BCT and associated radiation therapy. All of them were suspected to have tumor recurrence by clinical examinations, periodic mammographic examination and or ultrasonography. All the patients were submitted to dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) followed by magnetic resonance spectroscopy (MRS) at 1.5 T MRI machine.

Results

Local recurrence was confirmed by histopathology in 19 patients, MRS detected 18 patients with sensitivity of 94.7%, false positive was seen in one patient in whom histopathology revealed inflammatory mastitis (specificity 85.7%). One patient was false negative diagnosed by histopathology as ductal carcinoma in situ (DCIS) with negative predictive value of 85.7% and overall accuracy of 92.3%.

Conclusion

In our study breast MRS using choline (Cho) integral was accurate in evaluating patients with recurrent breast masses after BCT and radiation therapy. It reaches a high level of diagnostic performance.     

磁共振波谱技术在乳腺癌诊断中的应用

乳腺癌是临床常见的恶性肿瘤之一,MR在乳腺癌的诊断中发挥着重要的作用。磁共振波谱技术是能检测体内生化代谢的微创性检查方法,本文介绍磁共振波谱在乳腺癌诊断和评价治疗效果中的应用现状。     

Proton magnetic resonance spectroscopy in disturbances of cortical development

Proton magnetic resonance spectroscopy(¹H-MRS) can be used for looking at cerebral metabolites in vivo. However, measurement of concentrations of cerebral metabolites in patients with disturbances of cerebral development have not been successful. Our purpose was to measure the concentrations of cerebral metabolites in such patients. We carried out quantitative ¹H-MRS in eight patients with cortical dysplasia, four with lissencephaly and three with heterotopic grey matter and six age-matched normal controls. Regions of interest for ¹H-MRS were set over the affected cortex in the patients and the occipital cortex in controls. The calculated concentration of N-acetylaspartate ([NAA]) was significantly lower in the affected cortex in patients with cortical dysplasia (P < 0.05), lissencephaly (P < 0.01), and heterotopia (P < 0.05) than in controls, idnicating a decreased number and/or immaturity or dysfunction of neurones in the affected cortex. The concentration of choline ([Cho]) was significantly lower in patients with lissencephaly (P < 0.01) than in controls, indicating glial proliferation and/or membrane abnormality. Received: 19 April 2000 Accepted: 30 May 2000     

前列腺癌的质子磁共振波谱研究进展

早期诊断对前列腺癌预后至关重要。传统诊断方法均有较大的局限性。磁共振波谱可从代谢水平早期诊断前列腺癌。其技术的进展、可检测代谢物的特点以及对前列腺癌诊断和鉴别诊断、定位和体积估算、分级及侵袭力的评估、治疗后评价的临床研究均显示出明显的优势。     

Proton magnetic resonance spectroscopy in brain tumours: clinical applications

Parallel to the rapid development of clinical MRI, MR spectroscopy (MRS) has, after starting as an analytical tool used in chemistry and physics, evolved to a noninvasive clinical examination. Most common neuroradiological diagnostic indications for MRS are functional inborn errors, neonatal hypoxia, ischaemia, metabolic diseases, white matter and degenerative diseases, epilepsy, inflammation, infections and intracranial neoplasm. Compared to CT and MRI, well-established morphological diagnostic tools, MRS provides information on the metabolic state of brain tissue. We review the clinical impact of MRS in diagnosis of tumours and their differentiation from non-neoplastic lesions. Received: 3 April 2000 Accepted: 1 September 2000     

磁共振在诊断弥漫性轴索损伤中的应用进展

弥漫性轴索损伤是脑外伤的严重类型,也是影像学诊断的难点。随着软硬件的更新和新序列的研发应用,MRI在弥漫性轴索损伤的诊断中起着越来越重要的作用。本文将磁共振成像各个序列对弥漫性轴索损伤的应用情况综述如下。     

Proton magnetic resonance spectroscopy reflects cellular proliferative activity in astrocytomas

We examined whether proton magnetic resonance spectroscopy (MRS) could provide accurate information on histological grade and cell proliferation in astrocytomas. We studied 23 patients with astrocytomas: five grade II, 10 grade III and eight with grade IV (glioblastoma multiforme). We performed proton MRS and determined the Ki-67 labeling index (LI), a tumour proliferation marker, in the same areas of the astrocytomas, and examined the statistical relationship between proton MRS and Ki-67 LI. The N-acetylaspartate (NAA)/creatine-phosphocreatine (Cr) and NAA/choline (Cho)-containing compound ratios were always significantly lower and the Cho/Cr ratios significantly higher than those for normal brain. The Cho/Cr ratio correlated positively and the NAA/Cho ratio inversely with Ki-67 LI. These findings suggest that the Cho signal in proton MRS reflects cellular proliferation. In Kaplan-Meier survival analysis, there was no significant difference between high (> 2.0, 14 cases) and low (< 2.0, 9 cases) Cho/cr ratio groups. Received: 24 December 1998/Accepted: 11 August 1999     

Differentiation between high-grade glioma and metastatic brain tumor using single-voxel proton MR spectroscopy

The purpose of this study was to clarify the efficacy of single-voxel proton magnetic resonance spectroscopy (MRS) in differentiating high-grade glioma from metastasis. Thirty-one high-grade gliomas (11 anaplastic gliomas and 20 glioblastomas) and 25 metastases were studied. Proton MRS was performed using point-resolved spectroscopy with echo times (TEs) of both 136 and 30 ms. The peaks for lipid were evaluated at short TE, and those for N-acetyl-aspartate (NAA), creatine (Cr), and choline-containing compounds (Cho) were assessed at long TE. All the tumors exhibited a strong Cho peak at long TE. Twenty-one of 25 metastases showed no definite Cr peak. The remaining 4 metastases showed NAA and Cr peaks; however, the presence of NAA and relatively high NAA/Cr ratio (1.58+/-0.56) indicated normal brain contamination. All the gliomas, except for a single glioblastoma, showed a Cr peak with (n=16) or without (n=14) NAA. At short TE all metastases and glioblastomas showed definite lipid or lipid/lactate mixture, but anaplastic gliomas showed no definite lipid signal. Intratumoral Cr suggests glioma. Absence of Cr indicates metastasis. Definite lipid signal indicates cellular necrosis in glioblastoma and metastasis, and no lipid signal may exclude metastases.     

小儿流行性乙型脑炎磁共振波谱特征及随访研究

目的：探讨磁共振氢质子波谱（1H-MRS）对小儿流行性乙型脑炎预后评价的价值。方法：对17例常规MRI有信号异常的乙脑患儿行1H-MRS扫描,并选择15例同龄健康志愿者对照。病例组在3个月内进行随访并复查MRI,根据随访结果将患者分治愈组和未治愈组,回顾性分析两组患儿首次1H-MRS特征。结果：病灶在T1WI呈斑片状等或稍低信号、T2WI及FLAIR呈稍高或高信号,其中累及灰质核团13例,均呈对称性分布,边界清晰。17例患儿中1H-MRS均见不同高度Lac峰,7例NAA峰有明显下降,2例Cho峰轻度降低,1例出现Cr峰下降,3例出现MI峰。病例组与对照组之间NAA/（Cr＋Cho）值差异有显著性意义（t=5.98,P〈0.05）。根据随访结果,治愈组11例,未治愈组6例,两组NAA/（Cho＋Cr）差异有显著性意义（t=3.45,P〈0.05）。结论：乙脑患儿病变易累及灰质核团,1H-MRS多见Lac双峰,NAA明显下降往往提示患儿病情较重,预后不良。1H-MRS能反映乙脑严重程度并判断预后,是常规MRI有益补充。     

Proton magnetic resonance spectroscopy of brain tumors correlated with pathology

RATIONALE AND OBJECTIVES: Evaluate proton magnetic resonance spectroscopy ((1)H-MRS) for assessing and grading brain tumors. MATERIALS AND METHODS: The research was done at Detroit Medical Center in a 1.5-T Siemens MR magnet using single-voxel or multivoxel MRS. This study consisted of 27 patients: 10 females and 17 males ages 22-83 years (average age 43.8). The data were recorded for three peaks-N-acetyl aspartate (NAA), choline (Cho), creatine (Cr)-which were used to calculate the ratios Cho/NAA and Cho/Cr. RESULTS: Abnormal spectra were seen in 25 patients and normal spectra in 2. In 16 patients with brain astrocytoma of various grades, the pathology grading was correlated with Cho/NAA and Cho/Cr. These values were 6.53 and 3.35 for nine patients with Grade 4 astrocytoma; 1.85 and 1.62 for three patients with Grade 3 astrocytoma; 2.21 and 1.50 for three patients with Grade 2 astrocytoma; and 1.45 and 1.49 for one patient with Grade 1 astrocytoma. The remaining nine patients with abnormal spectra were also correlated with pathology. CONCLUSION: MRS ratios can be used to differentiate malignant and nonmalignant lesions from normal brain tissue. In general, high-grade astrocytoma have higher Cho/NAA and Cho/Cr ratios compared with low-grade astrocytoma.     

Role of brain magnetic resonance spectroscopy in the evaluation of suspected mitochondrial diseases in children: Experience in 30 pediatric cases

Introduction

Mitochondrial diseases are a group of inherited disorders caused by derangement of mitochondrial respiration. MR spectroscopy (MRS) has been shown to detect abnormal accumulation of lactate in brain parenchyma and CSF in patients with mitochondrial disorders, but the frequency of detection is largely unknown.

Aim of the work

To evaluate the role of brain MR spectroscopy in the assessment of suspected mitochondrial diseases in the pediatric age group.

Patients and methods

Thirty children with suspected mitochondrial diseases were examined by MRS. Examination was done using multisection technique and multiple echo times mainly short (35 ms) and intermediate (144 ms). Mitochondrial disease criteria scoring system was used to confirm the suspected diagnosis.

Results

All patients showed elevated lactate peak with the CSF being the most sensitive (100%). Among the 30 patients, 26 (86.7%) had elevated levels of blood lactate/pyruvate ratio. Conventional MRI showed highly suggestive features in 15 patients while non specific findings were detected in 11 patients and 4 showed normal appearing brain.

Conclusions

MRS provides a noninvasive tool for the diagnosis of mitochondrial diseases, especially in children with non specific findings on MRI, normal appearing MRI or a normal blood lactate/pyruvate ratio.     

Diagnosing dural metastases: the value of 1H magnetic resonance spectroscopy

The purpose of this study was to assess the value of MRI, MR spectroscopy (MRS) and intra-arterial angiography in the preoperative diagnosis of extra-axial dural-based masses. We prospectively studied 54 patients who underwent preoperative MRI, MRS and angiography. Histologically there were 50 meningiomas and four dural metastases. MRI and angiography did not allow reliable differentiation between meningiomas and metastases. MRS showed elevated choline/creatine ratios in both meningiomas and metastases, but there were prominent lipid signals in all metastases and a lactate peak in two. This spectroscopic pattern was not found in meningiomas. However, following embolisation, they showed similar spectra, due to ischaemia and necrosis. We therefore believe MRS to be valuable in differential diagnosis of dural metastases and meningiomas prior to embolisation. Received: 4 April 2000 Accepted: 6 October 2000     

Phosphorus-31 magnetic resonance spectroscopy of experimentally induced arthritis in rats

Phosphorus-31 magnetic resonance spectroscopy (MRS) of the hind paws of rats was performed at 1.5 Tesla before and during the course of an experimentally-induced inflammatory arthritis. Arthritis was induced by daily subcutaneous administration of 6-sulfanilamidoindazole, an antibacterial sulfa known to produce an acute, self-limited arthritis and periarthritis in the hind paws of rats.Phosphorus-31 spectra obtained after the development of clinical arthritis showed a significant (p<0.01) increase in the intensity of a group of resonances occurring downfiled from phosphocreatine as compared to spectra obtained before treatment. In all rats, this increase correlated well with histological evidence of inflammation as well as with the degree of inflammation judged clinically (r=0.89, p<0.001), and was present before roentgenographic evidence of bony involvement. The use of ³¹P MRS may permit evaluation of the severity of an inflammatory arthritis with greater accuracy than the bony changes definable by plain roentgenograms.This article is the award-winning Resident Paper of the International Skeletal Society for the year 1986. Support for its presentation at the annual meeting was contributed by the Department of Radiology of the University of British Columbia