| [Objective]1,To explore the value of hydrogen proton magnetic resonance spectroscopy (1-MRS) and diffusion tensor imaging (DTI) in detecting bilateral temporal lobe brain tissue damage in nasopharyngeal carcinoma after radiotherapy;2,To investigate the H-MRS imaging and DTI changes of temporal lobe brain tissue radiation injury in nasopharyngeal carcinoma after radiotherapy with compare to control group of normal;3,Trough analyze the radiation-induced brain damage in 1H-MRS imaging and DTI changes in nasopharyngeal carcinoma after radiotherapy in patients with different stages, to investigate the application of 1H-MRS imaging and DTI in monitoring brain radiation injury in the long-term follow-up after radiotherapy.[Materials and Methods]1. Investigate objectsConventional and enhanced MRI scan, DTI and 1H-MRS examination were performed in 48 cases of nasopharyngeal carcinoma patients after radiotherapy (radiotherapy group) and 24 volunteers (control group) during March to September of 2009, all of them were the same period in our hospital imaging center routine physical examination. All patients selected for radiotherapy group are as follows:1) nasopharyngeal carcinoma were diagnosed by histopathology; 2) have a clear history of radiotherapy and it's the first time; 3) chemotherapy plan before radiotherapy and radiation treatment are close (including the total dose of radiotherapy, partition number, the total radiotherapy time); 4) pre-radiotherapy imaging examination no clear signs show invasion of the base of skull and brain metastasis, without brain tumors, no history of cerebrovascular disease and intracranial surgery; 5) after radiotherapy MRI examination had no significant temporal lobe brain tissue liquefaction necrosis. Control group were selected as follows:routine health examination for the same period in our hospital imaging center, all the selected volunteers had no clinical symptoms of discomfort, no history of intracranial lesions, no history of serious vascular disease and cancer, no history of exposure to large doses of radiation, no abnormal signal change in brain in MRI examination.2. General information and groupThe radiotherapy group were 48 cases,32 cases were male,16 cases were female, aged 16 to 74 years old, with a median age of 46 years. The control group were 24 cases,13 males and 11 females, aged 26 to 74 years old, with a median age of 44 years. All patients included in the study were fully informed the purpose of testing and notes, and agreed to participate in the test. Radiotherapy group, with clinical symptoms in 18 cases, of which 8 cases of realization of headache,6 patients had hearing loss, tinnitus and decreased visual acuity were 2 cases respectively.-48 cases after radiotherapy were divided into 3 groups in accordance with the method of commonly group used at home and abroad after radiotherapy. Group as following: radiation-induced brain injury in acute and early delayed reaction(the time after the radiotherapy was less than 6 months)were group 1 (16 cases), changes in this period in the brain tissue were edema and mild demyelination mainly; radiation-induced brain injury in late delayed reactions after radiotherapy of 6 to 12 months were group 2 (6 cases), this period changes in brain tissue were gliosis mainly and the functional recovery partly of nerve fibers; After radiotherapy more than 12 months were group 3(26 cases). 3. MRI scanning methodsMRI examination adopt the United States, GE signa excite 3.0T superconductive MRI scanners, image post-processing using software in ancillary ADW 4.3 workstation. Conventional and contrast enhanced MRI scan using eight-channel head coil, receiving T1-weighted images (T1WI), T2-weighted images (T2WI) and water suppression image(FLAIR) respectively.1H-MRS imaging using two-dimensional multi-voxel spectroscopic imaging acquisition mode, the pulse sequences using point resolved spectroscopy (PRESS), TR/TE:1500/144ms, voxel thickness 10mm, spacing 20mm, NEX 1. Located in the the layer of the pons, choose a layer which bilateral temporal lobe white matter showed the greatest regions, VOI size according to specific circumstances, including bilateral temporal lobe white matter as much as possible, to avoid the base of the skull and sphenoid sinus. After positioning start MRI scan when the FWHM< 16, the water suppression (WS)≥98%. The total scan time was 8 min 12 s. DTI scan using ordinary head coil, imaging parameters:TR/TE:8000/87.4 ms, b value was 1000 s/mm2, proliferation-sensitive gradient direction number 25 direction, slice thickness 5 mm, total scan time 3 min 44 s.4. Image post-processing and data measurementUsing GE ADW4.3 workstation to make post-processing, use the software "Functool" open the multi-voxel 1H-MRS signal data and T2WI position image simultaneously,can get chemical shift map, spectral map, metabolism, and-metabolic and anatomical diagram integration map, choose 3 fixed-voxel in the bilateral temporal lobe white matter respectively. The 3 voxel were have higher signal noise ratio(SNR), and the MR spectroscopy curve have straight baseline and significantly narrow spectroscopy peaks. The software can receive the absolute value of the three major metabolites (choline (Cho), N-acetylaspartic acid (NAA) and creatine (Cr)) in the bilateral temporal lobe white matter automatically, and can receive NAA/Cho, NAA/Cr, Cho/Cr ratio simultaneously. Using the average of the 3 ratio value in the bilateral temporal lobe white matter as the final metabolite ratio value.After opened DTI scan data using Functool software on the workstation directly can receive three images automatically, T2WI as the original location map, fractional anisotropy(FA) map and apparent diffusion coefficient (ADC) map respectively. By converting can also received the three eigenvalues (λ1,λ2,λ3) images. Find the layer as close to the spectral location T2WI anatomy firstly, that is the scope of bilateral temporal lobe pons showed better level of white matter in the side of the white matter, then choosing the size of close to 3 regions of interest (ROI), The size of ROI were 30±5mm2.3 ROI positioned on the side of the lower corners of lateral ventricle adjacent to the temporal lobe white matter, and the 3 ROI pitch as far as possible equal, make a symmetrical line, using the software comes with mirror-symmetrical manner can received the three ROI in contra lateral temporal white matter, in some patients the organizational structure is not entirely symmetrical with bilateral brain scan images, make the appropriate adjustments to make ROI in the white matter.5. Statistical analysisAll data obtained are indicate as the mean±standard deviation ((?)±s), SPSS 13.0 software was used for statistical analysis, the level of test a was 0.05, P<0.05 consider that the difference was statistically significant. H-MRS and DTI data obtained using two independent samples t test, analyze the control group and all radiotherapy patients whether the differences between the two groups was statistically significant, and then all after radiotherapy cases were divided into 3 groups, using one-way analysis of variance (one-way ANOVA) compared radiotherapy group and the control group, if differences between the groups is statistically significant, then use LSD-t test to compare their differences two by two. Two-independent samples t test was used to analyze the difference of the age of radiotherapy group and control group, using Pearson x test comparing whether the gender differences between the two groups is statistically significant.[Results]1. Radiotherapy group compared with the control group no statistically significant difference in age (t=.016, P=0.988), compared between the two groups there were no significant gender differences statistically significant (x2=1.067, P=0.302). 2.1H-MRS data results:All radiotherapy in patients with MR examination in bilateral temporal lobe brain tissue were no significant abnormal signal change.(1) NAA/Cho ratio:The control group's NAA/Cho ratio was 1.265±0.102, radiotherapy group 0.997±0.123, the differences between them was significantly (t=11.822, P<0.001). Radiotherapy group was divided into 3 groups, each group NAA/Cho according to the time after radiotherapy were 0.910±0.112,0.972±0.101,1.060±0.095, the one-way analysis of variance shows the differences of them and control group was statistically significance (F=75.442, P< 0.001),4 groups LSD-t test comparison, the 3 groups after radiotherapy were compared with the control group and among them were statistically significant differences (P= 0.000), radiotherapy groups NAA/Cho ratio decreased than those in normal group. Group 3 of the NAA/Cho (after radiotherapy time more than 12 months) compared with the Group 1 and 2, differences were, statistically significant (P values were 0.000,0.014), compared with the previous the ratio of the two groups increased.(2) NAA/Cr ratio:Control group was 1.422±0.183, radiotherapy group 1.188±0.234, the differences between radiotherapy group and the control group was statistically significant (t=5.486, P<0.001). The NAA/Cr ratio of 3 groups after radiotherapy were 1.212±0.237,1.209±0.183,1.229±0.236 respectively, and the one-way ANOVA shows difference between the 4 groups was statistically significant (F=1 1.831, P<0.001).4 groups of comparison, NAA/Cr ratios of each group after radiotherapy decreased than those in control group, the differences were statistically significant (P<0.01). The difference between 0～6 months after radiotherapy (group 1) and the time after radiotherapy more than 12 months (group 3) was statistically significant (P=0.033), NAA/Cr ratio of the time after radiotherapy more than 12 months group increased compared with 0 to 6 months group.(3) Cho/Cr ratio:Control group was 1.374±0.285, radiotherapy group 1.290±0.198, difference of Cho/Cr ratio between radiotherapy group and the control group was no significant (t=1.660, P=0.103). Cho/Cr ratio of 3 groups after radiotherapy according to the time after radiotherapy were 1.280±0.175,1.259±0.222,1.303± 0.209 respectively,4 groups of one-way analysis of variance have no statistically significant difference between groups (F=1.346, P=0.263).3. DTI data results:(1) FA values:The normal control group's FA value was 0.474±0.024, all the radiotherapy group was 0.456±0.023, and difference between normal control group and radiotherapy group was statistically significant (t=4.436, P<0.001). FA values of the three groups after radiotherapy were 0.445±0.017,0.460±0.016,0.461±0.025 respectively. The one-way analysis of variance shows the difference between the 4 groups including control group was statistically significant (F=10.873, P<0.001). The results of LSD-t test was:the FA values of group 1,3 decreased compared with the normal group and the differences between them were statistically significant (P <0.01). The FA value of the Group 2,3 is slightly higher than Group 1 and the differences were statistically significant (P<0.05).(2) ADC values:The normal control group's ADC value was 8.686±0.570×10-4mm2/s, the value of all the radiotherapy group was 8.449±0.370×10-4mm2/s, t test shows statistically significant differences between the two groups (t=2.623, P=0.011). ADC values of the three groups after radiotherapy were 8.510±0.429×10-4mm2/s,8.483±0.337×10-4mm/s,8.404±0.338×10-4mm2/s, with the normal group, the difference of four groups were compared between groups was statistically significant (F=3.399, P=0.020), LSD-t test in between control group and the Group 3 shows statistically significant difference (P<0.05), the control group compared with the Group 1 was no statistically significant difference. ADC values displays a steady decline compared with the control group with the extension of time after radiotherapy.(3) The eigenvalue date:the maximum eigenvalueλ1 of the control group was 1.350±0.091×10-5mm2/s, radiotherapy group 1.296±0.077×10-5mm2/s, differences between the two groups was statistically significant (t=3.749, P<0.001).λ1 of the three groups after radiotherapy were 1.252±0.062×10-5mm2/s,1.293±0.052×10-5mm2/s,1.323±0.078×10-5mm2/s. The difference between the 4 groups was statistically significant (F=10.660, P< 0.001), the maximum eigenvalue in each group after radiotherapy significantly decreased compared with the control group, and its change trend with close to the FA value changes, that is Group 1 decreased significantly compare with the control group (P= 0.000), the Group 2,3 have recovered than Group 1 but still slightly lower than control group (P value is 0.121,0.000 respectively). The differences between control group and 3 groups after radiotherapy was statistically significant in the middle eigenvaluesλ2 and minimum eigenvalueλ3 (F values were 3.608,2.855 and P values were 0.015,0.039 respectively).The value of group 1 higher than the control group inλ2 andλ3.[Conclusion]1. DTI and 1H-MRS examination are more sensitive than conventional MRI on detecting radiation-induced injury of bilateral temporal lobe brain tissue in nasopharyngeal carcinoma after radiotherapy. In all selected radiotherapy group, conventional MRI imaging including T1WI, T2WI and FLAIR in bilateral temporal lobe brain tissue were no obvious abnormal signal, DTI examination can measured significant changes in FA values, ADC value and eigenvalue, The ratios between NAA, Cho, Cr three metabolites of 1H-MRS examination have changed also.2. Contrast the normal group, radiation injury of the nasopharyngeal carcinoma after radiotherapy of bilateral temporal lobe brain tissue performance the NAA/Cho ratio decreased significantly, NAA/Cr ratio slightly decreased in'H-MRS imaging, both compare with the control group, difference was statistically significant. While the Cho/Cr is a slight drop but have no statistical difference; The FA value decreased and ADC value of slight drop in DTI imaging, the maximum eigenvalueλ1 reduced and the minimum eigenvalueλ3 lightly raised.3.1H-MRS changes and significance in different stages of radiation-induced injury after radiotherapy:In the early radiation-induced brain injury, NAA/Cho were significantly reduced, the MR spectroscopy curve showed the NAA peak lower than Cho, indicating an early change was NAA decline, which reflects the major changes of neuronal cell dysfunction and some axonal structural damage in early white matter radiation-induced injury; NAA/Cho ratio shows a slight recovery late, but compare with the control group remained lower, and after radiotherapy long period of time can not be restored, it reflects that though acute and sub-acute phase of radiation brain injury can partly recovered, but some axonal structural damage can not be remodeling in the long-term; Cho/Cr ratio of radiotherapy groups and the control group comparison have no significant difference, perhaps because of Cho changes more complex, radiation-induced vascular injury and tissue ischemia caused cell membrane synthesis reduced, which makes Cho concentration decreased, while the glial cells hyperplasia reactively and cell membrane structural damage and collapse, can lead to Cho increased.4. DTI changes and significance in different stages of radiation-induced injury after radiotherapy:radiation-induced brain injury in acute and early delayed reaction period, the FA value decreased obviously, and accompanied by the maximum eigenvalueλ1 decline, the minimum eigenvalueλ3 and the middle eigenvalueλ2 raise, indicating the main changes of after radiotherapy within 6 months of radiation brain injury is demyelination, nerve fibers and axon integrity destroyed and reduction of the number, at the same time with a certain degree of glial cells proliferation response to radiotherapy; 6-12 months after radiotherapy FA values start to rise, the maximum eigenvalueλ1 has also been increased, indicating that early damage in whiter matter can be self-healing partly, while declination ofλ2 andλ3 note of demyelination was slightly alleviated, oligodendrocytes have begun to replace and the nerve axon function was partially restored; But after radiotherapy more than 12 months ever for a longer time, FA values continued to rise but can not restored to normal level, it was still slightly lower than the control group, indicating a late axonal damage and neuronal cell number reduction were difficult to restore. ADC value decreased compared with the control group may be related to radiotherapy bring about vascular endothelial cells increased, cells edema, and glial cell reactive hyperplasia, inflammatory cell infiltration.
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