Clinical Application Of MR Functional Techniques In The Evaluation Of Cerebral Glioma Invasiveness And Comparison With Immunohistochemical Study

PrefaceGlioma is the most common primary brain tumor. The clinical course and treatment method are different according to various grade of the tumor. Astrocytomas account for the majority of gliomas. Oligodendrocytomas and oligoastrocytomas are the second common gliomas. The clinical symptom is less severe and there is longer survival time for oligodendrocytoma and oligoastrocytoma comparing with astrocytoma. They are very allergic to the radiotherapy and chemotherapy. Presurgical determination of malignancy degree and the type of histology of cerebral gliomas plays an important role in clinical work. The morphologic changes of the tumor cells are the golden standard of glioma grading. But the histological specimen can only be obtained by invasive surgery or biopsy. It is difficult to get the accurate malignant degree of the glioma because of inevitable sampling error. How to judge the invasiveness of the tumor accurately is a tough problem for clinical doctors. Routine MR imaging plays a very important role in the morphological diagnosis of gliomas. The application of MR functional techniques makes the diagnosis of glioma to the microscopic scale which provides both morphological changes and biochemical functions. They can also provide the quantitative analysis in some degree and become the necessary complementary methods for routine MR examinations.Our studies begin with the metabolism of gliomas. We use the most commonly used ratios of metabolism that been got from proton MR spectroscopy (¹HMRS) to differentiate astrocytomas and oligodendroglioma or oligodendroastrocytoma. We also use them to investigate various enhanced area of glioma. For the first time, we compared MRS with PCNA (proliferating cell nuclear antigen) and survivin of astrocytomas in order to get the theoretic proof of the ability that MRS can assess the malignancy and invasiveness of gliomas. Meanwhile, DTI was studied in the assessment of malignancy of supra-tentorial gliomas. The correlation between DTI manifestations and clinical manisfestations was performed to evaluate the invasion of gliomas to the pyramidal tracts. We engaged in the study of the metabolism and histopathologic study noninva-sively. The morphologic and functional studis are equally emphasized. It may offer the objective criterion to the therapy and prognosis of gliomas.Materials and MethodsThe study group was composed of two sub-groups. The first sub-group included 50 patients of astrocytoma (29 men and 21 women, age range 11-74 years, with a median age of 45.18 years): Low-grade astrocytoma (WHO gradeâ…¡) in 10 patients, anaplastic astrocytoma (WHO gradeâ…¢) in 21 patents and glioma multiform (WHO gradeâ…£) in 19 patients. The second sub-group included 10 patients (5 men and 5 women; age range from 13 to 47 years, with a median age of 31.50 years): oligoden-droglioma (WHO gradeâ…¡) in 3 patients, oligodendroastrocytoma (WHO gradeâ…¡) in 1 patient, anaplastic oligodendroglioma (WHO gradeâ…¢) in 3 patients, anaplastic oligodendroastrocytoma (WHO gradeâ…¢) in 3 patients. The control group included 20 healthy volunteers. All the studies were informed to all the subjects and acceptances were obtained from all of them. The examinations included routine precontrast T₁ weighted spin-echo imaging (T₁WI), T₂ weighted spin-echo imaging (T2WI), ¹HMRS examination and postcontrast T₁WI. They were performed with GE Signa MR/ior Excite HD 1.5 T superconductive MR system. The raw data was imported to GE workstation. MRS images and met-anatomic images were obtained with Functiontool software. The maximal values of Cho/NAA and Cho/Cr and the minimal value of NAA/Cr in the tumor parenchyma, peri-tumorous region and contralateral brain were recorded. The ratios of tumour Cho,NAA,Cr to the contralateral side(Cho/nCho,NAA/nNAA,Cr/nCr) were also recorded. The immunohistochemical stainings of PCNA and survivin were performed for all the astrocytomas. The proliferative index(PI) of PCNA and im-munoreactive score(IRS) of survivin were obtained. The metabolism ratios of astrocytomas were compared by one way ANOVA. Independent- samples t test was used for the comparison between astrocytomas and gliomas with oligodendrocyte. Pared-samples t test was used for analysis between the strongest enhanced regions and the less enhanced or non-enhanced regions of the high grade gliomas. Separate statistical comparisons of the three MRS parameters (met-ratios of Cho/NAA,Cho/Cr and NAA/Cr) with PI values of tumors, the met-ratios with IRS values were made using Pearson correlation analysis. Statistical software (SPSS 13.0) was used for analysis and P values of less than 0.05 were considered to indicate a statistically significant difference.Twenty-three patients with supra-tentorial gliomas confirmed by surgery were also included in this study (12 men and 11 women; age range from 22 to 71 years, with a median age of 45.91 years). This group included low-grade glioma (WHO gradeâ…¡) in 7 patients and high-grade glioma in 16 patients (WHO gradeâ…¢in seven patients and WHO grade IV in nine patients). Eleven patients experienced preoperative sensorimo-tor deficits (low-grade glioma in 1 patient, anaplastic glioma in 3 patients, glioblastoma in 7 patients). The rest 12 cases didn't suffer from sensorimotor deficits. Conventional gadolinium-DTPA enhanced T₁WI, and diffusion-tensor imaging (DTI) were performed before surgical resection using GE Signa Exicite HD 1.5 T superconductive MR machine with a 8-channel phased-array head and neck coil. A single-shot spin-echo echo-planar sequence with axial-plane was applied for DTI. Diffusion gradients encoding in 25 directions with b=1000s/mm² and 0 s/mm² were performed. Statistic analysis was made by using Mann-Whitney U test and 2-sided pared t test.Results1. Application of ¹HMRS in the human brain gliomasThe met ratios of Cho/Cr and Cho/NAA in the low-grade astrocytomas were lower than high-grade astrocytomas (WHO gradeâ…¢and gradeâ…£) (P<0.05) and the met ratio of NAA/Cr was higher than high-grade astrocytomas (P<0.05), but there were no significant deviations of the met ratios within high-grade astrocytomas (P>0.05). The ratios of Cho/NAA and Cho/Cr in the peri-tumorous region in low grade astroctyomas were lower than that in high grade astrocytomas (P<0.05) and NAA/Cr was higher than that of high grade astrocytoma (P<0.05). The ratio of Cho/NAA in astrocytomas gradeâ…¢in the peri-tumorous region was lower than that of gradeâ…£(P<0.05), but there was no significant deviation of Cho/Cr and NAA/Cr between gradeâ…¢and gradeâ…£astro- cytomas (P>0.05).The met ratios of Cho/Cr and Cho/NAA were higher in oligodendrogliomas and oligodendroastrocytomas than astrocytomas of the same grade (P<0.05), but there was no significant difference of NAA/Cr between them (P>0.05). The ratios of Cho/nCho,Cr/nCr and NAA/nNAA were higher in the less or non-enchanced region than the most significant enhanced region(P<0.05).2.¹HMRS manifestation of astrocytomas in patients and the compare study with the PCNA and survivin of the post-surgery specimenThe IRS of survivin and PI of PCNA were higher accompanying the higher grade of gliomas. There was a strongly positive correlation between the ratio of Cho/Cr and IRS (r=0.745, P<0.01), and also between the ratio of Cho/NAA and IRS (r=0.753, P<0.01). We found strongly positive correlation between the ratio of Cho/Cr and PI (r=0.818, P<0.01), and between the ratio of Cho/NAA and PI (r=0.760, P<0.01). There was a weak negative correlation of NAA/Cr with IRS (r=-0.374, P<0.01) and PI(r=-0.436, P<0.01).3. Application of DTI in the grading and evaluation of invasiveness of supra-tentorial gliomasThe MD value in the peritumoural region of low grade glioma was higher than the solid part of the glioma and lower than the necrotic and cystic region, but the FA value was higher than those region (P<0.01). The MD value in the peri-tumoural region of high grade glioma was higher than the tumour parenchyma (P<0.01), but there was no significant difference of FA values between them (P>0.05). There were significant differences in MD and FA values of the peri-tumoural regions within the high grade gliomas (P<0.01), but there were no differences in the FA values of parenchyma and cystic region between them (P>0.05).There were no significant deviations for the MD and FA values of pyramidal tracts in the plane of posterior limb of internal capsule,cerebral peduncle and pons of low grade glioma between the two sides(P>0.05). The FA value in the ipsilateral side was lower than contralateral location in the section of posterior limb of internal capsule (P<0.01). There was no significant difference in the other two planes. The MD values in all the planes were similar between the two sides (P>0.05). In patients suffering sensorimotor deficits, we found significantly decreased FA and increased MD for the ipsilateral pyramidal tracts in the plane of internal capsule, but for the patients without deficits, there were no differences in the MD and FA values on all the planes between two sides (P>0.05).All the pyramidal tracts were clearly showed by the diffusion tensor tractography. There were 12 patients (WHO gradeâ…¡in six patients, gradeâ…¢in four patients and gradeâ…£in two patients) had normal or approximately normal fiber tracts (type one). There were shifts of the pyramidal tracts with abnormal pseudo-color of MD and FA (type two) in the 10 cases. There was obvious invasion and interruption of some fibers in the rest one case. We didn't find completely interruption of the fibers in all the group of patients. All of the patients suffering sensorimotor deficients had the pyramidal tract changes of type two and three and the symptoms relieved or disappeared postsurgery.ConclusionMRS examination is very helpful for astrocytomas in grading and discrimination with oligodendroglioms and ologodendroastrocytomas. The contents of metabolisms are different in the nonhomogeneous enhanced gliomas. The biopsy of the weak enhanced or non-enhanced region is suggested respecting there is more Cho,Cr and NAA in that region.MRS has strongly correlation with the protein manifestation of PCNA and sur-vivin of astrocytomas. MRS provides a helpful and noninvasive method in the preop-erative assessment of apoptosis,reproductive activity,invasive activity and predicting the prognosis of astrocytomas. The ratios of Cho/Cr and Cho/NAA are more useful than NAA/Cr.Measurements of MD and FA values from DTI in the tumor parenchyma and peri-tumoural region are assisted in differentiation between high-grade and low-grade gliomas. We have found changes of FA and MD values outside the tumor abnormal-appearing region on T2WI. The measurements of FA and MD values of pyramidal tracts on different sections are very helpful in revealling the pathologic changes of the deficient patients which are not detectable on conventional MR imaging. The reconstruction of pyramidal tracts shows us the three-dimensional relationship of the fiber bundles and gliomas. In addition, it can show us the micro changes of the pyramidal tracts by adding the pseudo-colour of MD and FA values. DTI in combination with fiber tracking can provide more important imformations which are very helpful in making the plan of surgery and prognostic assessment of the patient with glioma.