Ruihao Wang

Comparison of SPECT/CT, MRI and CT in diagnosis of skull base bone invasion in nasopharyngeal carcinoma.

Early detection of skull base invasion in nasopharyngeal carcinoma (NPC) is crucial for correct staging, assessing treatment response and contouring the tumor target in radiotherapy planning, as well as improving the patients prognosis. To compare the diagnostic efficacy of single photon emission computed tomography/computed tomography (SPECT/CT) imaging, magnetic resonance imaging (MRI) and computed tomography (CT) for the detection of skull base invasion in NPC. Sixty untreated patients with histologically proven NPC underwent SPECT/CT imaging, contrast-enhanced MRI and CT. Of the 60 patients, 30 had skull base invasion confirmed by the final results of contrast-enhanced MRI, CT and six-month follow-up imaging (MRI and CT). The diagnostic efficacy of the three imaging modalities in detecting skull base invasion was evaluated. The rates of positive findings of skull base invasion for SPECT/CT, MRI and CT were 53.3%, 48.3% and 33.3%, respectively. The sensitivity, specificity and accuracy were 93.3%, 86.7% and 90.0% for SPECT/CT fusion imaging, 96.7%, 100.0% and 98.3% for contrast-enhanced MRI, and 66.7%, 100.0% and 83.3% for contrast-enhanced CT. MRI showed the best performance for the diagnosis of skull base invasion in nasopharyngeal carcinoma, followed closely by SPECT/CT. SPECT/CT had poorer specificity than that of both MRI and CT, while CT had the lowest sensitivity.

Disturbance of the let-7/LIN28 double-negative feedback loop is associated with radio- and chemo-resistance in non-small cell lung cancer

Radio- and chemo-resistance represent major obstacles in the therapy of non-small-cell lung cancer (NSCLC) and the underlying molecular mechanisms are not known. In the present study, during induction of radio- or chemo-resistance in NSCLC cells, dynamic analyses revealed that decreased expression of let-7 induced by irradiation or cisplatin resulted in increased expression of its target gene LIN28, and increased expression of LIN28 then contributed to further decreased expression of let-7 by inhibiting its maturation and biogenesis. Moreover, we showed that down-regulation of let-7 and up-regulation of LIN28 expression promoted resistance to irradiation or cisplatin by regulating the single-cell proliferative capability of NSCLC cells. Consequently, in NSCLC cells, let-7 and LIN28 can form a double-negative feedback loop through mutual inhibition, and disturbance of the let-7/LIN28 double-negative feedback loop induced by irradiation or chemotherapeutic drugs can result in radio- and chemo-resistance. In addition, low expression of let-7 and high expression of LIN28 in NSCLC patients was associated significantly with resistance to radiotherapy or chemotherapy. Therefore, our study demonstrated that disturbance of the let-7/LIN28 double-negative feedback loop is involved in the regulation of radio- and chemo-resistance, and that let-7 and LIN28 could be employed as predictive biomarkers of response to radiotherapy or chemotherapy in NSCLC patients.

Optimal beam arrangement for pulmonary ventilation image-guided intensity-modulated radiotherapy for lung cancer

BackgroundThe principal aim of this study was to evaluate the feasibility of incorporating four-dimensional (4D)-computed tomography (CT)-based functional information into treatment planning and to evaluate the potential benefits of individualized beam setups to better protect lung functionality in patients with non-small cell lung cancer (NSCLC).MethodsPeak-exhale and peak-inhale CT scans were carried out in 16 patients with NSCLC treated with intensity-modulated radiotherapy (IMRT). 4D-CT-based ventilation information was generated from the two sets of CT images using deformable image registration. Four kinds of IMRT plans were generated for each patient: two anatomic plans without incorporation of ventilation information, and two functional plans with ventilation information, using either five equally spaced beams (FESB) or five manually optimized beams (FMOB). The dosimetric parameters of the plans were compared in terms of target and normal tissue structures, with special focus on dose delivered to total lung and functional lung.ResultsIn both the anatomic and functional plans, the percentages of both the functional and total lung regions irradiated at V5, V10, and V20 (percentage volume irradiated to >5, >10 and >20 Gy, respectively) were significantly lower for FMOB compared with FESB (P < 0.05), but there was no significant difference for V30 (P > 0.05). Compared with FESB, a greater degree of sparing of the functional lung was achieved in functional IMRT plans with optimal beam arrangement, without compromising target volume coverage or the irradiated volume of organs at risk, such as the spinal cord, esophagus, and heart.ConclusionsPulmonary ventilation image-guided IMRT planning with further optimization of beam arrangements improves the preservation of functional lung in patients with NSCLC.

Volume and dosimetric variations during two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal carcinoma.

The aims of this study were to evaluate the volume and dosimetric variations during IMRT for locally advanced NPC and to identify the benefits of a two-phase adaptive IMRT method. Twenty patients with locally advanced NPC having received IMRT treatment were included. Each patient had both an initial planning CT (CT-1) and a repeated CT scan (CT-2) after treatment at a dose of 40 Gy. Three IMRT planning scenarios were compared: (1) the initial plan on the CT-1 (plan-1); (2) the hybrid plan recalculated the initial plan on the CT-2 (plan-2); (3) the replan generated on the CT-2 being used to complete the course of IMRT (plan-3). The mean gross target volume and mean volumes of the positive neck lymph nodes, high-risk clinical target volume, and the left and right parotid glands significantly decreased by 30.2%, 45.1%, 21.1%, 14.7% and 18.2%, respectively on the CT-2. Comparing plan-2 with plan-1, the dose coverage of the targets remained unchanged, whereas the dose delivered to the parotid glands and spinal cord increased significantly. These patients with locally advanced NPC might benefit from replanning because of the sparing of the parotid glands and spinal cord.

The Feasibility of Mapping Dose Distribution of 4DCT Images with Deformable Image Registration in Lung

Calculating an accurate cumulative dose through individual phases for four-dimensional computed tomography (4DCT) images from the lung is time-consuming. Although the dose distribution of different phases is similar, copying the dose distribution of one phase directly to another phase would yield a dosimetric error of approximately 4% without further optimization. To reduce the dosimetric error, three-dimensional B-spline elastic deformable image registration (DIR) was used to quickly obtain a relatively accurate cumulative dose of 4DCT images acquired from ten lung cancer patients. The dose distribution of the end-expiration phase was mapped to the end-inspiration phase using DIR. The mapped dose in the end-inspiration phase was then compared with the directly copied dose by analysis (3cm/3%) and the t-test. The results showed that optimization using DIR was significantly better in the average pass rate (by 0.6-4.7%). Our results indicate it is feasible to map the dose distribution of 4DCT images in lung with DIR, and that the motion amplitude of individual respiratory and different DIR algorithms affect the differences between the mapped and actual dose.

4D-CT reconstruction based on pulmonary average CT values

To date, commercial 4D-CT systems typically depend on an external respiratory monitoring device. Immobilizing patients in a thermoplastic mask while receiving radiotherapy may result in a failure of 4D-CT reconstruction. The aim of this study is to investigate the feasibility of 4D-CT reconstruction based on a method using pulmonary average CT values (ACV) without an external respiratory monitoring device. The ACV of the whole lung assumes cyclical variation during respiration. Phases of CT images were identified by calculating the ACV over time. Subsequently, five sets of 4D-CT images based on a Real-time Position Management (RPM) system were selected to verify the ACV method. The entire lung CT datasets of another sixteen free-breathing patients were acquired in Cine scan mode for multiple couch positions. The phase of every CT image was identified and re-sorted into different phase 4D-CT volumes by analyzing the time dependence of the corresponding ACVs. This paper demonstrates the ACV method using the 4D-CT data sets based on the RPM system. Convenient and reliable 4D-CT reconstruction can be accomplished without any external respiratory monitoring device using ACVs.

Dosimetric study of the deformable image registration based lung cancer adaptive radiotherapy

The purpose of this study is to evaluate the dosimetric gain of the adaptive radiotherapy (ART) over conventional intensity modulated radiation therapy (IMRT) by using as the deformable image registration technique for dose mapping and summation to assess the dosimetric difference on target and organs at risk (OARs) dose. We retrospectively collected planning CT images and fractional CT images from nine lung cancer patients who were treated with adaptive IMRT. During fractional treatments, new tumor and organ contours are generated using the deformable image registration and a new IMRT plan is generated for the follow up treatments for each patient. The resulting deformation moving vector fields are also used to map and accumulate dose from the first 20 fractions to the sequential 10 fractions for final total dose calculation. The organs at risk (OARs) and the tumor of dosimetric parameters are compared between the ART and conventional IMRT plan. The evaluation results showed that when using the ART technique, the mean GTV volume is reduced by 53.2%, the mean tumor dose is increased by 0.41Gy, the mean lung V20 and V30 are decreased by 2.17% and 3.32%, the mean heart V30 and V40 are decreased by 1.14% and 2.98%, respectively, and the maximum dose of spinal cord is decreased by 1.21Gy when compared with the conventional IMRT. This work demonstrated the feasibility of ART to achieve better target coverage and OARs sparing over the conventional IMRT, and it will potentially reduce the radiation side effect and increase the local control rate.

An anthropomorphic abdominal phantom for deformable image registration accuracy validation in adaptive radiation therapy

Purpose To design and construct a three‐dimensional (3D) anthropomorphic abdominal phantom for geometric accuracy and dose summation accuracy evaluations of deformable image registration (DIR) algorithms for adaptive radiation therapy (ART). Method Organ molds, including liver, kidney, spleen, stomach, vertebra, and two metastasis tumors, were 3D printed using contours from an ovarian cancer patient. The organ molds were molded with deformable gels made of different mixtures of polyvinyl chloride (PVC) and the softener dioctyl terephthalate. Gels with different densities were obtained by a polynomial fitting curve that described the relation between the Hounsfield unit (HU) and PVC‐softener blending ratio. The rigid vertebras were constructed by molding of white cement and cellulose pulp. The final abdominal phantom was assembled by arranging all the fabricated organs inside a hollow dummy according to their anatomies, and sealed by deformable gel with averaged HU of muscle and fat. Fiducial landmarks were embedded inside the phantom for spatial accuracy and dose accumulation accuracy studies. Two channels were excavated to facilitate ionization chamber insertion for dosimetric measurements. Phantom properties such as deformable gel elasticity and HU stability were studied. The dosimetric measurement accuracy in the phantom was performed, and the DIR accuracies of three DIR algorithms available in the open source DIR toolkit‐DIRART were also validated. Results The constructed deformable gel showed elastic behavior and was stable in HU values over times, proving to be a practical material for the deformable phantom. The constructed abdominal phantom consisted of realistic anatomies in terms of both anatomical shapes and densities when compared with its reference patient. The dosimetric measurements showed a good agreement with the calculated doses from the treatment planning system. Fiducial‐based accuracy analysis conducted on the constructed phantom demonstrated the feasibility of applying the phantom for organ‐wise DIR accuracy assessment. Conclusions We have designed and constructed an anthropomorphic abdominal deformable phantom with satisfactory elastic property, realistic organ density, and anatomy. This physical phantom can be used for routine validations of DIR geometric accuracy and dose accumulation accuracy in ART.

Reduction in stray radiation dose using a body‐shielding device during external radiation therapy

&NA; With the purpose of reducing stray radiation dose (SRD) in out‐of‐field region (OFR) during radiotherapy with 6 MV intensity‐modulated radiation therapy (IMRT), a body‐shielding device (BSD) was prepared according to the measurements obtained in experimental testing. In experimental testing, optimal shielding conditions, such as 1 mm lead, 2 mm lead, and 1 mm lead plus 10 mm bolus, were investigated along the medial axis of a phantom using thermoluminescent dosimeters (TLDs). The SRDs at distances from field edge were then measured and analyzed for a clinical IMRT treatment plan for nasopharyngeal carcinoma before and after shielding using the BSD. In addition, SRDs in anterior, posterior, left and right directions of phantom were investigated with and without shielding, respectively. Also, the SRD at the bottom of treatment couch was measured. SRD decreased exponentially to a constant value with increasing distance from field edge. The shielding rate was 50%‐80%; however, there were no significant differences in SRDs when shielded by 1 mm lead, 2 mm lead, or 1 mm lead plus 10 mm bolus (P>0.05). Importantly, the 10 mm bolus absorbed back‐scattering radiation due to the interaction between photons and lead. As a result, 1 mm lead plus 10 mm bolus was selected to prepare the BSD. After shielding with BSD, total SRDs in the OFR decreased to almost 50% of those without shielding when irradiated with IMRT beams. Due to the effects of treatment couch and gantry angle, SRDs at distances were not identical in anterior, posterior, left and right direction of phantom without BSD. As higher dose in anterior and lower dose in posterior, SRDs were substantial similarities after shielding. There was no significant difference in SRDs for left and right directions with or without shielding. Interestingly, SRDs in the four directions were similar after shielding. From these results, the BSD developed in this study may significantly reduce SRD in the OFR during radiotherapy, thus decreasing the risk of secondary cancers.

Analysis of setup error based on CTVision for nasopharyngeal carcinoma during IGRT

The aim of the present study was to investigate the role of CTVision in interfractional setup errors during intensity‐modulated radiation therapy (IMRT) in 12 nasopharyngeal carcinoma (NPC) patients. The trend of setup errors as a function of time during a fractionated radiotherapy course was investigated, and the influence of reconstructive thickness on image reconstruction for setup errors was analyzed. The appropriate planning target volume (PTV) margin and planning risk volume (PRV) margin were defined to provide a reference for the design of IMRT for NPC. Based on CTVision, online CT was performed weekly for each patient. Setup errors were measured by registration between the CT reconstructed image and reference image. Mean of setup errors, estimated population systematic (:), and population random (σ) errors were calculated using SPSS (v15.0). Optimum PTV and PRV margins were calculated. In the clinical data, for the LR (left–right), SI (superior–inferior), and AP (anterior–posterior) directions, : was 0.8, 0.8, and 1.0 mm, respectively, and σ was 1.0, 1.3, and 0.8 mm, respectively. In the LR, SI, and AP directions, PTV margins were at least 2.7, 2.9, and 3.0 mm, respectively, and PRV margins were at least 1.5, 1.7, and 1.7 mm, respectively. No significant differences in setup errors were observed during the fractionated radiotherapy course (p>0.05). However, CT image reconstruction with different thicknesses affected the accuracy of measurements for setup errors, particularly in the SI direction. The application of CTVision to correct setup errors is important and can provide reasonable margins to guarantee the coverage of PTVs and spare organs at risk. A thickness of 3 mm in the reconstructed image is appropriate for the measurement of setup errors by image registration. PACS number(s): 87.55.QrThe aim of the present study was to investigate the role of CTVision in interfractional setup errors during intensity-modulated radiation therapy (IMRT) in 12 nasopharyngeal carcinoma (NPC) patients. The trend of setup errors as a function of time during a fractionated radiotherapy course was investigated, and the influence of reconstructive thickness on image reconstruction for setup errors was analyzed. The appropriate planning target volume (PTV) margin and planning risk volume (PRV) margin were defined to provide a reference for the design of IMRT for NPC. Based on CTVision, online CT was performed weekly for each patient. Setup errors were measured by registration between the CT reconstructed image and reference image. Mean of setup errors, estimated population systematic (:), and population random (σ) errors were calculated using SPSS (v15.0). Optimum PTV and PRV margins were calculated. In the clinical data, for the LR (left-right), SI (superior-inferior), and AP (anterior-posterior) directions, : was 0.8, 0.8, and 1.0 mm, respectively, and σ was 1.0, 1.3, and 0.8 mm, respectively. In the LR, SI, and AP directions, PTV margins were at least 2.7, 2.9, and 3.0 mm, respectively, and PRV margins were at least 1.5, 1.7, and 1.7 mm, respectively. No significant differences in setup errors were observed during the fractionated radiotherapy course (p>0.05). However, CT image reconstruction with different thicknesses affected the accuracy of measurements for setup errors, particularly in the SI direction. The application of CTVision to correct setup errors is important and can provide reasonable margins to guarantee the coverage of PTVs and spare organs at risk. A thickness of 3 mm in the reconstructed image is appropriate for the measurement of setup errors by image registration. PACS number(s): 87.55.Qr.