1. Early detection and diagnosis of ARILI
　　At present comprehensive clinical diagnosis (history of radiotherapy, signs and symptoms , peripheral blood test and imaging examination) and follow-up evaluation are commonly used, where the imaging examination, especially HRCT, provides the most direct evidence for the diagnosis of ARILI [7,8,14]. However, studies indicate that when positive ARILI diagnosis is made by HRCT, the RILI in most patients has progressed into irreversible phase [15]. HRCT visualizes the general morphological changes of lesions. However, according to studies in brain tissue and other organs, morphological changes imaged with CT have relatively low sensitivity and significantly lag behind alterations in perfusion metrics. Therefor, HRCT is mainly useful to detect RILI in the late phase and to evaluate the effectiveness of radiotherapy and the diagnostic and prognostic capabilities of HRCT are very limited. Although ECT can perform lung perfusion and morphological examination [16-17], its specificity, sensitivity and spatial resolution are low, and has disadvantages such as mono-index, complicated computation and radiation pollution that limit its application in RILI diagnosis. The effectiveness of TGF and TNF in peripheral blood for ARILI diagnosis is still controversial and with points of disagreement and opposing conclusions [18-19].
　　Studies of RILI with CTPI, to our knowledge, have been rarely reported in literature, and in this study we attempted to determine the hemodynamic patterns of regional lung tissue using quantitative analysis of regional lung tissue CTPI metrics before and after irradiation. 
2. General trend in CTP parameters at different time point after irradiation
　　In this study, comparison of the perfusion parameters of the non-irradiated lung field, in either ARILI or non ARILI group, showed no statistically significant differences, indicating that radiotherapy did not affect the non-irradiated field. This is concordant with the fact that ARILI occurs in the irradiated field, where radiation induced injuries resulting in direct impairment of cells in the region.
　　In the non-ARILI group, the relative perfusion parameters of irradiated lung field increased along with the dose administered and time of therapy (week 4 to week 8), then decreased gradually after completion of the radiotherapy. On the whole, the perfusion curve demonstrated a pattern of “slow-rise to slow-fall”. Given this pattern, the rrBF and rrBV obtained before and after radiation were compared and statistically significant differences were found. However, rrPS demonstrated no statistically changes. This change likely represents hyperemia seen at the level of capillary vessels, possibly along with mild exudation and mild edema, occurring in lung tissue during the course of radiation in this non-ARILI group. However these mild changes could not be detected by HRCT imaging. At the same time, capillary endothelial cells and alveolar cells also had minor damage[17,20], which most likely lead to the slightly increased rrPS. However, the change in pre- and post-radiotherapy was not statistically significant. The most important point here is that most of these minor changes were reversible, and that tissue repair occurred after radiation (in week 8). The perfusion parameters started to return to normal level and finally became normal, which illustrates that there was no fundamental impairment in capillary endothelial cells or alveolar cells and they were repaired, as the cellular injury was within repair capability of the tissue.
    In this study there were 18 patients in ARILI group, so the incidence of ARILI was 35%, which was consistent with the reports in the literature [21,22]. Using the perfusion values before radiotherapy as the benchmark, in the ARILI group, perfusion parameters demonstrated rapid increase within the first 8 weeks of radiotherapy, and continued increasing slowly in week 12, showing the patterns of “rapid-rise to slow-fall” or “rapid-rise to flat”. By comparing the perfusion parameters before and after the radiotherapy, statistically significant differences were found, particularly for the difference of PS. The pathological process of ARILI includes alveolar epithelial cells and pulmonary capillary endothelial cell injury, causing exposure and damage to pulmonary capillary endothelium, basilar membrane, and alveolar membrane. Ultimately inflammatory exudate formation is gradually induced[17,23]. Pathologically, these changes result in pulmonary congestion and increase in permeability of capillaries. CTPI results in this study were consistent with the pathological process described above, especially the PS index changes. An interesting finding in this study indicates that ARILI did not occur in those patients with the increased BF and BV, but did occur, when PS increased together with BF and BV. This phenomenon suggests that the PS reflects the pathological process of ARILI, and is superior to HRCT in terms of detecting early ARILI. At week 8 and week 12 after radiotherapy, along with the continued impairment of capillary endothelial and alveolar epithelial cells, pulmonary capillary lumen becomes congested with substantial amount of monocytes, erythrocytes and leucocytes. Infiltration of lymphocytes, histiocytes and plasmacytes into the pulmonary interstitium also increases [24-25], and fibrocytes and fibroblasts increase in proliferation and differentiation, therefore at this stage abnormalities can be observed on HRCT images [26]. However, at this stage, RILI has entered the middle phase of pathological process (2 - 9 months after radiotherapy).
3. Value of CTPI for early diagnosis of ARILI
　　In ARILI group, comparison of rrPS in week 4, week 8 and week 12 with rrPS measured before radiation or with rrPS in non-ARILI group demonstrated statistically significant differences. This means that change in permeability of capillaries is the most significant change in ARILI, and the rrPS better reflects this pathological change. As a result, abnormality in rrPS may represent a reliable indicator of ARILI and represents a promising new method for early ARILI detection and prediction.
　　In this study, the sensitivity, specificity, positive predictive value and negative predictive value of ARILI diagnosis was high when using rrPS at half-dose stage of irradiation (week 4 after radiotherapy), which was statistically significantly superior to HRCT. In week 8 and week 12, the percentage of ARILI cases positive on HRCT increased but was still lower than cases positive on CTPI. 6 ARILI cases developed from level 0-1 (in week 4) to level 2-4 (in week 8) and presented typical HRCT manifestations, which indicated diagnostic reliability of CTPI for ARILI diagnosis at the half-dose stage of radiation.  7 cases presented with ARILI in week 8 and week 12 did not show positive CT manifestation in week 4. But the rrPS, rrBF, and rrBV increased to some degree in week 4, most evident in changes of rrPS, wich suggests that CTPI may diagnose and predict ARILI, though this predictive capability needs to be further investigated with a larger number of subjects.

4. CTPI protocols and radiation dose
　　Due to requirements of 3D-CRT, CT imaging is needed for selection of reduced radiation field for therapy, monitoring of short term therapy effectiveness and assessment of response to therapy. CT imaging is necessary at least three times : before, during and after the radiotherapy for patients with thoracic tumor. Non contrast and post contrast CT is usually obtained for this purpose. CT perfusion scan range covers the tumor region, and can serve as a substitute for post contrast CT, as reconstructed images similar to the post contrast CT can be obtained after acquisition of CT perfusion imaging. As a result, the CT examination in this study includes pulmonary parenchyma CT perfusion followed by whole lung CT scan, replacing the conventional non-contrast and post-contrast CT. In this way, hemodynamic parameters and conventional CT images are obtained at the same time. For lung perfusion scanning, the average dose length product (DLP) was 539mGy·cm, and the effective radiation dose was about 9.16 mSv, which are significantly lower than that of conventional examination (non contrast and post contrast CT) for which mean effective radiation dose was 14.21 mSv.
　　In conclusion, values of CTPI parameters may reflect hemodynamic changes in the lungs after radiation therapy, and may detect ARILI earlier than HRCT, representing a promising new technique for early diagnosis of ARILI.