| Part one:Dynamic MRS study on radiation-induced brain injury in nasopharyngeal carcinomaObjectiveThrough the dynamic MRS follow-up of the received radiotherapy for nasopharyngeal carcinoma patients with bilateral temporal lobe of the brain tissue to radiotherapy during and after radiotherapy within 12 months, to monitor the change of the major metabolite content process and trend, and compare elderly group and young group in the metabolite content variations in the process of radiotherapy.From July 2013 to December 2015,80 patients of the Hainan Provincial People’s Hospital were initially diagnosed with nasopharyngeal cancer through imaging examination and nasopharyngeal lesion biopsy (excluding other brain and systemic diseases). Conventional magnetic resonance imaging (MRI) and MRS imaging were performed before radiotherapy and at the radiotherapy doses of 20,40, and 60 Gy. Of the 80 patients,47 underwent MRS follow-up 6 and 12 months after radiotherapy (the other 33 cases were excluded from this group owing to the long follow-up interval time or loss to follow-up, including 36 males and 11 females, aged 37 to 63 years old).61 cases were male,19 female, age ranged from 28 to 72 years, of which 55 cases with elderly patients (age more than 45 years old), average age (60±4), youth groups (age less than 45 years old) in 25 cases, with an average age of (37±8)years. Radiation therapy involved the face-neck joint portal, nasopharynx, and neck. The lower part of the bilateral temporal lobe was included in the radiation field. The conventional fractionation method was 2 Gy/day,5 times a week. This study was conducted in accordance with the Declaration of Helsinki and with approval from the Ethics Committee of People’s Hospital of Hainan Province. Written informed consent was obtained from all participants.MRS scanning used the high resolution 3D T2WI positioning on MPRAGE sequence. Each spectral scanning range as much as possible of the same, referred to their respective first scanned bitmap, bilateral temporal lobes and hippocampus of a symmetrical front within the scanning range.The data collected were sent to the equipment processing workstation. The Functool software was used in post-processing and analysis. The small voxel within spectral scanning with the size of about 30 ± 5 mm2 was automatically analyzed by the software. In the bilateral tem-poral lobe,2 small voxels with the highest signal-to-noise ratios and ideal spectral curves were selected for analysis. The bilateral concentration ratios of the major metabolites, N-acetyl aspartate (NAA), creatine (Cr), and choline (Cho), and the average of NAA/Cr, Cho/Cr, and Cho/NAA were determined to analyze the change trends of the metabolite concentration ratios during the early period of reaction.Statistical analysis was performed using SPSS 18.0 statistical software. Spectral data are reported as means ± SD. The data before radiotherapy were regarded as covariates. At different time points during the early delayed reaction phase, the NAA/Cr, Cho/Cr, and NAA/Cho values were subjected to repeated measures analysis of variance. P< 0.05 was considered to be statistically significant, and Receiver operating characteristic (ROC) curve were used for statistical analysis.ResultOf the 80 nasopharyngeal cancer cases with initial radiotherapy,47 cases underwent MRS follow-up up to the 12th month after therapy. During this period, the use of neurotrophic drugs, vasodilator, and hormones were not allowed.The trends of the concentration ratios of the 3 main metabolites were described. 1) Compared with those before radiotherapy, NAA/Cr, Cho/Cr, and NAA/Cho values were reduced during and after radiotherapy.2) Three months after radiotherapy, the 3 ratios were further reduced, and the amplitude was less than that during the radiation process, the three values reached to the lowest level,compared with the data after radiotherapy, the differences were statistically significant (t=-8.298,-9.596,-9.957, P=0.000,0.000,0.000), the area of the NAA/Cr, Cho/Cr and NAA/Cho values under the ROC curve were 0.547,0.582 and 0.500.3) Increasing trends were observed from the 4th to the 12th month after radiotherapy. On the 12th month, the 3 ratios were higher than those after radiotherapy to varying degrees. The Cho/Cr and NAA/ Cho values were close to but still lower than the pre-radiotherapy values.4)The ratios of NAA/Cr, Cho/Cr before radiotherapy were 1.94 ±0.15,1.87+0.20 in the elderly group, and 1.95 ±0.22,1.83±0.24 in the young group respectively, but the difference was not statistically significant (t=-0.221,0.612, P=0.826,0.543). At the radiation with dosages of 20,40,and 60 Gy, the ratios of NAA/Cr were 1.92±0. 26,1.54±0.16,1.07±0.08 in the elderly group respectively, and were 1.94±0. 27,1.93±0.21,1.76±0.18 in the young group respectively. There were statistical differences between two groups (t=-0.261,-7.187,-19.241,respectively, P=0.795, 0.000,=0.000).ConclusionThe cure dose of radiation therapy induces the risk of damage to normal tissue surrounding the radiation field. The effect of radiotherapy positively correlates with the radiation dose. Increasing the dose also increases the risk of normal brain tissue damage. Neuronal damage exhibits functional and metabolic disorders after radio-therapy. MRS monitors the changes in metabolite concentration during radiation-induced brain injury in the early delayed reaction period. Thus, MRS is beneficial in the assessment of the extent of repair and prognosis of radiation-induced brain damage. The neurons of aged patients with nasopharyngeal carcinoma have weak tolerance to the radiation, brain injury occurr earlier and heaver related to young patients. Since the injury is smallest at the dose of 20 Gy among the doses evaluated, the intervention conducted in the elderly patients at this dose may help to minimize the injury to the neurons.Part two:Diffusion tensor imaging study on radiation-induced brain injury in nasopharyngeal carcinoma during and after radiotherapyObjectiveThe aim of this study was to monitor the mircostructure change of temporal lobe during the acute and subacute stage of radiation-induced brain injury using magnetic resonance diffusion tensor imaging (DTI) in nasopharyngeal carcinoma patients.Materials and MethodsPatients were all as the same as the first part.Patients with nasopharyngeal carcinoma combined with other brain diseases, systemic metabolic diseases,immune disorders, or temporal lobe defect were excluded. Cases with upward growth nasopharyngeal carcinomawere selected in this study and the radiation beam was mainly concentrated in the temporal lobe. All patients were treated with the first radiotherapy through the faciocervical field. The irradiated sites included the nasopharynx, neck, and bilateral temporal lobe. A standard fractionation radiotherapy (2.0 Gy/d,5 days per week) was performed. Informed consent was obtained from patients before therapy and examination. Routine brain MRI and DTI were conducted in all patients before and during radiotherapy (radiation dose was 20 Gy,40 Gy, and 60 Gy, respectively). For 47 cases of 80 patients, the examinations were also performed in the 3rd,6th, and 12th month after radiotherapy, respectively.All the examinations were performed in the same superconductive MRI scanner (Siemens Verio 3.0T). The routine MRI sequences included axial plane T1-weighted imaging,T2-weighted imaging,and T2 fluidattenuated inversion recovery (FLAIR), Axial plane echoplanar imaging was used for DTI, with scope and layer in line with T2 FLAIR.The imaging parameters were as follows:TR,6000 ms; TE,40 ms; layer thickness,5.0 mm; interval,0; field of view,24 cm x 24 cm; resolution,128× 128; number of excitations,1; b value,1000 s/mm2. The DTI map was obtained from the diffusion sensitive gradient of 25 linear directions.On the DTI map, the bilateral anterior temporal lobe was selected as region of interest to measure the average diffusion coefficient (ADC) and fractional anisotropy (FA) value, respectively. In order to avoid overlap between brain tissue and target region, the location and voxel size of each measurement were the same. The skull base sclerotin and bilateral ventricular temporal horn were avoided.Statistical analysis was performed using SPSS 18.0 statistical software. Data are expressed as mean ± SD. One-way analysis of variance and Student t test were performed to determine the statistically significant differences among different groups. p<0.05 was considered as statistically significant, and Receiver operating characteristic (ROC) curve were used for statistical analysis.ResultNo patients were treated with hormone, neurotrophic drug, or vasodilator during the observation stage. No obvious cerebral edema, intracranial hypertension, or nerve injury was detected by routine brain MRI. The colors of bilateral anterior temporal lobe on ADC and FA pseudocolor image were close. There was no obvious color difference between anterior and posterior parts of the bilateral temporal lobe.The ADC values were increased and the FA values were decreased with the increase of radiation dose (20,40, and 60 Gy) during the radiotherapy, but there was no significant difference of ADC value or FA value between before radiotherapy and during radiotherapy (p>0.05). Compared with before radiotherapy, the ADC values were significantly increased and the FA values were significantly decreased at the 3rd month after radiotherapy (t=-25.152,-4.227,P=0.000,0.000), and the area of ADC and FA value under the ROC curve were 0.737,0.172 respectively. At the end of radiotherapy after 6-12 months ADC and FA value gradually returned to the trend before radiotherapy, but were higher and lower than before the treatment respectively.At the end of radiotherapy (80 cases) and the 3th,6th,12th month after radiotherapy (47 cases in 80 cases), DTT imaging were compared with itself before and after radiotherapy respectively, by 2 professional radiology diagnosis of doctors consultation and confirmation. According to the distribution of fiber bundle, shape and continuity of the state is divided into 3 grades:Grade 1, fiber the continuous beam, the natural shape, without interruption and loss; Grade 2, the fiber bundle is complete, sparse, shape shift, not the nature; Grade 3, part of the fiber beam local interruption loss. At the end of radiotherapy,1 grade and 2 grade were 47 cases and 43 cases after radiotherapy,and had no significant difference; the third month after radiotherapy,16 cases of grade 1, grade 2 in 23 cases, grade 3 in 8 cases among them, cases of grade 2 and 3 increased after radiotherapy completed in the 6th month and the 12th month in some cases of fiber bundle shape tended to be minority before radiotherapy, and a few minority interrupted of fiber beam hah no eye changes.ConclusionDTI can showed microstructure changes of brain tissue before monitoring the abnormalities in conventional MRI.especially changes in the cerebral white matter microstructure.FA value, ADC value changes appeared in the process of radiotherapy, especially the FA value is more sensitive, further highlighted in the subacute phase with cell derived water swollen and aggravated vasogenic edema. DTI results consistent with the 1H-MRS results in the delayed response period. DTT can show the fiber bundle out of shape, form, etc. But it cannot be quantitatively compared, just to use visual observation for judging, it inevitably exist subjectivity. With brain tissue necrosis occurred in severe radiation-induced brain injury cases, DTT displaying the change of the number and morphology of the fiber bundle could be more intuitive, and its vdue can be better presented.Part there:MR dynamic susceptibility contrast perfusion study on radiation-induced brain injury in nasopharyngeal carcinomaObjectiveThis section is to study on the use of perfusion changes in patients with nasopharyngeal carcinoma on the basis of magnetic resonance spectroscopy MRS and DTI tensor imaging, to explore the characteristics of different stages during radiotherapy and after radiotherapy of bilateral temporal lobe brain tissue hemodynamic, to seek the role of vascular damage in NPC brain radiation injury, to provide an objective theory from the perspective of vascular injury for dynamic monitoring and evaluation radiation injury.Materials and MethodsThe inclusion and exclusion criteria is as same as the first part.PWI imaging was performed after MRS and DTI scanning.DSC-PWI was conducted in all patients before and during radiotherapy (radiation dose was 20 Gy,40 Gy, and 60 Gy, respectively). For 47 cases of 80 patients, the examinations were also performed in the 3rd,6th, and 12th month after radiotherapy, respectively. All the examinations were performed in the same superconductive MRI scanner (Siemens Verio 3.0T). GRE-EPI sequence parameters were as follows:TE=40 ms; TR=2000 ms; the flip angle is 90 degrees; the vision of 24; the thickness of 6 mm; the interval of 0.3 mm; incentive for 1. dynamic perfusion scanning parallel to the joint line the plane, including bilateral temporal lobe. The contrast agent was 469.01 mg/15 ml GD DTPA, the injection dosage is 0.20 mmol/kg, double tube high pressure syringed after bolus injection, the injection rate was 4 ml/s, after injection of contrast agent at the same rate 20.0ml normal saline was injected. MRI conventional scan pipeline in DSC-PWI after the acquisition performed:the scanning sequence including whole brain OSag-fsT1WI, OCor-fsT1WI and OAxi-fsT1WI. The data of DSC-PWI transmission sent to the device comes, its built-in functool software package was used for post processing, adjustment of CBV value of pseudo color pictures, in location map of the cerebral peduncle level bilateral temporal lobe and in the drawing two ROI in the bilateral temporal lobe, a total of four ROI data mean value for the analysis, to as much as possible to reduce the man-made factors with the error. The perfusion software could automatically get the cerebral blood flow, cerebral blood flow(CBF) and cerebral blood volume in cerebral blood volume (CBV) of graph parameters and the corresponding data.Statistical analysis was performed using SPSS 18.0 statistical software. Data are expressed as mean ± SD. One-way analysis of variance and Student t test were performed to determine the statistically significant differences among different stages. P< 0.05 was considered as statistically significant.Result1) Before radiotherapy, radiotherapy and radiotherapy after the 3th,6th and 12th month, bilateral temporal lobe cerebral blood flow high signal area approximately symmetrical, in part of cases observed asymmetry, and there were no significant changes in high sign area.2) Perfusion curve:inflow outflow portion substantially parallel with the baseline deep inverted peak before radiotherapy, after radiation therapy dose of 40Gy, perfusion curve can be observed change.3) Before radiotherapy CBV and CBF value were 1146.0±73.5(ml/min*100g),325.2±29.7 (ml/min*100g) respectively, at the end of radiotherapy were 1128.3±71.1, 314.9±47.5, there was no statistically significant difference (P> 0.05); there months after the end of radiotherapy, CBV and CBF were 709.5±66.6,171.6±22.7,respectively, compared with before radiotherapy, the difference was statistically significant (t=31.087,29.580,P=0.000.0.000); and the area of CBV and CBF value under the ROC curve were 0.867,0.856 respectively. From the 3th month to the 12th month after the end of radiotherapy, CBV and CBF values increased in different degrees, were 910.3±61.9,284.3±30.7 respectively at the end of the 12th month after radiotherapy, and lower than before treatment.ConclusionThe CBV and CBF perfusion index of MR dynamic magnetic susceptibility contrast perfusion imaging can reflect and embody microcirculation and tissue function, suggesting that bilateral temporal lobe at the edge of the radiation effects of radiation, target cerebral vascular structure and function of the corresponding changes involved in radiation brain injury. |
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