Evaluation of dosimetric variance in whole breast forward intensity modulated radiotherapy based on 4D CT and 3D CT.

To explore the dosimetric variance in forward intensity modulated radiotherapy (IMRT) based on 4D CT and 3D CT after breast conserving surgery. Seventeen patients after breast conserving surgery underwent 3D CT simulation scans followed by respiration-synchronized 4D CT simulation scans at free breathing state. The treatment plan constructed using the end inspiration (EI) scan was then copied and applied to the end expiration (EE), and 3D scans and dose distribution were calculated separately. Dose-volume histograms (DVHs) parameters for the CTV, PTV, ipsilateral lung and heart were evaluated and compared. The CTV volume difference was biggest between T0 and 3D CT, and the volume difference was 4.10 cm(3). Mean dose of PTV at EE was lower than that at EI (P = 0.019), but there were no statistically significant difference between 3D and EI, EE (all P > 0.05). The homogeneity index (HI) at EI, EE, 3D plans were 0.149, 0.159 and 0.164, respectively, and a significant difference was only between EI and EE (P = 0.039). The highest conformal index (CI) was at EI phase (P < 0.05), and there was no significant difference between EE and 3D (P = 0.758). The V(40) and V(50) of ipsilateral lung at EE phase were lower than that at EI (P < 0.05). There were no significant differences in all the indexes for heart (P > 0.05). The breast deformation during respiration may be disregarded in whole breast IMRT. PTV dose distribution is significantly changed between EI and EE phases, and the differentiation of the lung high dose area between EI and EE phases may be induced by thorax expansion. 3D treatment planning is sufficient for whole breast forward IMRT, but 4D CT scans assisted by respiratory gating ensures more precise delivery of radiation dose.

Analysis of Whole Breast Displacement Relative to Selected Skin Markers and Surgical Clips using Four-dimensional Computed Tomography

The accuracy of positron emission tomography (PET) quantification and localization can be compromised if a misregistered computed tomography (CT) is used for attenuation correction (AC) in PET/CT. As data-driven gating (DDG) continues to grow in clinical use, these issues are becoming more relevant with respect to solutions for gated CT. In this work, a new automated DDG CT method was developed to provide average CT and DDG CT for AC of PET and DDG PET, respectively. An automatic DDG CT was developed to provide the end-expiratory (EE) and end-inspiratory (EI) phases of images from low-dose cine CT images, with all phases being averaged to generate an average CT. The respiratory phases of EE and EI were determined according to lung region Hounsfield unit (HU) values and body outline contours. The average CT was used for AC of baseline PET and DDG CT at EE phase was used for AC of DDG PET at the quiescent or EE phase. The EI and EE phases obtained with DDG CT were used for assessing the magnitude of respiratory motion. The proposed DDG CT was compared to two commercial CT gating methods: (1) 4D CT (external device based) and (2) D4D CT (DDG based) in 38 patient datasets with respect to respiratory phase image selection, lung HU, lung volume, and image artifacts. In a separate set of twenty consecutive PET/CT studies containing a mix of 18 F-FDG, 68 Ga-Dotatate, and 64 Cu-Dotatate scans, the proposed DDG CT was compared with D4D CT for impacts on registration and quantification in DDG PET/CT. In the EE phase, the images selected by DDG CT and 4D CT were identical 62.5% ± 21.6% of the time, whereas DDG CT and D4D CT were 6.5% ± 9.7%, and 4D CT and D4D CT were 8.6% ± 12.2%. These differences in EE phase image selection were significant (p < 0.0001). In the EI phase, the images selected by DDG CT and 4D CT were identical 68.2% ± 18.9% of the time, DDG CT and D4D CT were 63.9% ± 18.8%, and 4D CT and D4D CT were 61.2% ± 19.8%. These differences were not significant. The mean lung HU and volumes were not statistically different (p > 0.1) among the three methods. In some studies, DDG CT was better than D4D or 4D CT in the appropriate selection of the EE and EI phases, and D4D CT was found to reverse the EE and EI phases or not select the correct images by visual inspection. A statistically significant improvement of DDG CT over D4D CT for AC of DDG PET was also demonstrated with PET quantification analysis. When irregular breath cycles were present in the cine CT, DDG CT could be used to replace average CT for the improved AC of baseline PET. A new automatic DDG CT was developed to tackle the issues of misregistration and tumor motion in PET/CT imaging. DDG CT was significantly more consistent than D4D CT in selecting the EE phase images as the clinical standard of 4D CT. When compared to both commercial gated CT methods of 4D CT and D4D CT, DDG CT appeared to be more robust in the lower lung and upper diaphragm regions where misregistration and tumor motion often occur. DDG CT offered improved AC for DDG PET relative to D4D CT. In cases with irregular respiratory motion, DDG CT improved AC over average CT for baseline PET. The new DDG CT provides the benefits of 4D CT without the need for external device gating.

New Data-Driven Gated (DDG) PET/CT for Radiation Treatment Planning of NSCLC

During gated intensity-modulated radiotherapy (IMRT) treatment for patients with inoperable non-small cell lung cancer (NSCLC), the end-expiration (EE) phase of respiratory is more stable, whereas end-inspiration (EI) spares more normal lung tissue. This study compared the relative plan quality based on dosimetric and biological indices of the planning target volume (PTV) and organs at risk (OARs) between EI and EE in gated IMRT. 16 Stage I NSCLC patients, who were scanned by four-dimensional CT, were recruited and re-planned. An IMRT plan of a prescription dose of 60 Gy per respiratory phase was computed using the iPlan treatment planning system. The heart, spinal cord, both lungs and PTV were outlined. The tumour control probability for the PTV and normal tissue complication probability for all OARs in the EE and EI phases were nearly the same; only the normal tissue complication probability of the heart in EE was slightly lower. Conversely, the conformation number of the PTV, V20 of the left lung, V30 of both lungs, Dmax of the heart and spinal cord, V10 of the heart and D5% of the spinal cord were better in EE, whereas D(mean) of the PTV, V20 of the right lung and maximum doses of both lungs were better in EI. No differences reached statistical significance (p<0.05) except Dmax of the spinal cord (p=0.033). Overall, there was no expected clinical impact between EI and EE in the study. However, based on the practicality factor, EI is recommended for patients who can perform breath-hold; otherwise, EE is recommended.

This study was performed to explore and compare the dosimetric variance caused by respiratory movement in the breast during forward-planned IMRT after breast-conserving surgery. A total of 17 enrolled patients underwent the 3DCT simulation scans followed by 4DCT simulation scans during free breathing. The treatment planning constructed using the 3DCT images was copied and applied to the end expiration (EE) and end inspiration (EI) scans and the dose distributions were calculated separately. CTV volume variance amplitude was very small (11.93 ± 28.64 cm3), and the percentage change of CTV volumes receiving 50 Gy and 55 Gy between different scans were all less than 0.8%. There was no statistically significant difference between EI and EE scans (Z =–0.26, P = 0.795). However, significant differences were found when comparing the Dmean at 3DCT planning with the EI and EE planning (P = 0.010 and 0.019, respectively). The homogeneity index at EI, EE and 3D plannings were 0.139, 0.141 and 0.127, respectively, and significant differences existed between 3D and EI, and between 3D and EE (P = 0.001 and 0.006, respectively). The conformal index (CI) increased significantly in 3D treatment planning (0.74 ± 0.07) compared with the EI and EE phase plannings (P = 0.005 and 0.005, respectively). The V30, V40, V50 and Dmean of the ipsilateral lung for EE phase planning were significantly lower than for EI (P = 0.001–0.042). There were no significant differences in all the DVH parameters for the heart among these plannings (P = 0.128–0.866). The breast deformation during respiration can be disregarded in whole breast IMRT. 3D treatment planning is sufficient for whole breast forward-planned IMRT on the basis of our DVH analysis, but 4D treatment planning, breath-hold, or respiratory gate may ensure precise delivery of radiation dose.

Objective To investigate the correlations of the whole breast displacement in different respiratory cycle during free breathing (FB) following breast-conserving surgery to the displacement of selected skin marker,nipple,and selected surgical clip based on four-dimensional computed tomography (4D-CT).Methods Thirteen breast cancer patients who had undergone breast-conserving surgery received whole breast intensity-modulated radiotherapy (IMRT).Respiration-synchronized 4D-CT image data were gathered during FB and were exported to the Varian Eclipse treatment planning system,and the whole breast target,nipple,superior clip,and metal marker on the skin at the anterior body midline were delineated on the CT images of ten phases of the respiratory cycle by the same radiotherapist based on the same delineating criteria.The displacement distances of the delineated target in the mediolateral (x),anteroposterior (y),and superoinferior (z) axles were achieved,and the correlations of the whole breast target displacement to the displacement of the clip,nipple,and skin marker were analyzed.The ipsilateral lung was delineated on the CT images of every phase of the respiratory cycle,and the changes in ipsilateral lung volume were analyzed during the respiratory cycle relative to the displacement of the breast.Results The maximal displacement distances of the whole breast target in the x,y,and z axles during FB were 0.71,0.76 and 1.29 mm,respectively ( F =5.755,P ＜ 0.05 ).There was no relationship between the three-dimensional (3D) displacement of the whole breast and the volume of the whole breast (r =-0.264,P ＜ 0.05 ),and there was no relationship between the displacemeat of the whole breast and the volume change of the ipsilateral lung ( r =0.346,P ＜ 0.05).There was no significant difference among the mean target displacement distances in 3 axles,and among 2 selected successive end-inspiration (EI) phases and 3 selected successive end-expiration (EE) phases.There was no significant difference between the volumes of the whole breast targets at the selected El and EE phases.There was no relationship between the displacement of the whole breast target and the displacement of the nipple,skin marker or superior clip in the cavity along the x- and z-axles.Along the y-axle,8/13,7/11 and 9/13 of the patients showed displacement of the whole breast target relative to the displacement of the nipple,skin marker and superior clip respectively.However,according to a population-based analysis,the displacement of the whole breast target was only significantly associated with the displacement of the superior clip ( r =0.657,P ＜ 0.05 ).Conclusions The clip registration is more credible and sensitive than a skin marker or the nipple for measuring and correcting the displacement of the whole breast target during radiotherapy. Key words: Breast-conserving treatment, radiotherapy; Target displacement; Fourdimensional computed tomography ; Skin-marker; Silver clip in cavity

Comparison of end normal inspiration and expiration for gated intensity modulated radiation therapy (IMRT) of lung cancer

Data-driven gated (DDG) PET has gained clinical acceptance and has been shown to match or outperform external-device gated (EDG) PET. However, in most clinical applications, DDG PET is matched with helical CT acquired in free breathing (FB) at a random respiratory phase, leaving registration, and optimal attenuation correction (AC) to chance. Furthermore, DDG PET requires additional scan time to reduce image noise as it only preserves 35%-50% of the PET data at or near the end-expiratory phase of the breathing cycle. A new full-counts, phase-matched (FCPM) DDG PET/CT was developed based on a low-dose cine CT to improve registration between DDG PET and DDG CT, to reduce image noise, and to avoid increasing acquisition times in DDG PET. A new DDG CT was developed for three respiratory phases of CT images from a low dose cine CT acquisition of 1.35mSv for a coverage of about 15.4cm: end-inspiration (EI), average (AVG), and end-expiration (EE) to match with the three corresponding phases of DDG PET data: -10% to 15%; 15% to 30%, and 80% to 90%; and 30% to 80%, respectively. The EI and EE phases of DDG CT were selected based on the physiological changes in lung density and body outlines reflected in the dynamic cine CT images. The AVG phase was derived from averaging of all phases of the cine CT images. The cine CT was acquired over the lower lungs and/or upper abdomen for correction of misregistration between PET and FB CT as well as DDG PET and FB CT. The three phases of DDG CT were used for AC of the corresponding phases of PET. After phase-matched AC of each PET dataset, the EI and AVG PET data were registered to the EE PET data with deformable image registration. The final result was FCPM DDG PET/CT which accounts for all PET data registered at the EE phase. We applied this approach to 14 18F-FDG lung cancer patient studies acquired at 2min/bed position on the GE Discovery MI (25-cm axial FOV) and evaluated its efficacy in improved quantification and noise reduction. Relative to static PET/CT, the SUVmax increases for the EI, AVG, EE, and FCPM DDG PET/CT were 1.67±0.40, 1.50±0.28, 1.64±0.36, and 1.49±0.28, respectively. There were 10.8% and 9.1% average decreases in SUVmax from EI and EE to FCPM DDG PET/CT, respectively. EI, AVG, and EE DDG PET/CT all maintained increased image noise relative to static PET/CT. However, the noise levels of FCPM and static PET were statistically equivalent, suggesting the inclusion of all counts was able to decrease the image noise relative to EI and EE DDG PET/CT. A new FCPM DDG PET/CT has been developed to account for 100% of collected PET data in DDG PET applications. Image noise in FCPM is comparable to static PET, while small decreases in SUVmax were also observed in FCPM when compared to either EI or EE DDG PET/CT.

To compare the position, displacement, degree of inclusion (DI) and matching index (MI) of the gross tumor volume (GTV) for peripheral lung cancer based on 4-dimensional CT (4D CT) and 3-dimensional CT (3D CT) assisted with active breathing control (ABC). Eighteen patients with peripheral lung cancer underwent 4D CT simulation scan during free breathing and 3D CT simulation scans in end-inspiratory hold (CTEIH) and end-expiratory hold (CTEEH) in turn. The 4D CT images from each respiratory cycle were sorted into 10 phases. phase 0 was defined as end-inspiratory phase (CT0), and phase 50 was defined as end-expiratory phase (CT50). The GTVs were delineated separately on CT0, CT50, CTEIH and CTEEH images, and then GTV0, GTV50, GTVEIH and GTVEEH were constructed, respectively. The median distances between the centroids of GTV0 and GTVEIH, GTV50 and GTVEEH were 3.9 mm and 3.4 mm in all patients, 3.2 mm and 3.1 mm in the upper lobe group, and 5.0 mm and 4.7 mm in the lower lobe group, respectively. In the upper lobe group, the GTV0 and GTVEIH were 65.9% and 63.1%, and the median mutual DIs of GTV50 and GTVEEH were 67.5%, 63.1%, respectively. In the lower lobe group, the GTV0 and GTVEIH were 35.3% and 21.4%, and the median mutual DIs of GTV50 and GTVEEH were 27.8% and 24.8%, respectively. In the upper lobe group, the median MI of GTV0 and GTVEIH was 0.5, and the median MI of GTV50 and GTVEEH was 0.6. In the lower lobe group, the median MI of GTV0 and GTVEIH was 0.2, and the median MI of GTV50 and GTVEEH was 0.3. Whether in the upper or lower lobe groups, all the differences between displacements of centroid positions of GTVEIH and GTVEEH (ABC displacement) and GTV0 and GTV50 (4D displacement ) were <1 mm in three dimensional directions (all P>0.05). The target displacement of tumors based on 3D CT scanning in end-inspiratory hold and end-expiration hold can be used to construct internal target volume instead of that based on 4D CT scanning in extreme phase for peripheral lung cancers, but spatital mismatches of GTVs are obvious between extreme phases in 4D CT and corresponding phases in 3D CT assisted with ABC, especially for tumors of smaller volume and with larger motion amplitude.

Misregistration between CT and PET data can result in mis-localization and inaccurate quantification of functional uptake in whole body PET/CT imaging. This problem is exacerbated when an abnormal inspiration occurs during the free-breathing helical CT (FB CT) used for attenuation correction of PET data. In data-driven gated (DDG) PET, the data selected for reconstruction is typically derived from the end-expiration (EE) phase of the breathing cycle, making this potential issue worse. The objective of this study is to develop a deformable image registration (DIR)-based respiratory motion model to improve the registration and quantification between misregistered FB CT and PET. Twenty-two whole-body 18 F-FDG PET/CT scans encompassing 48 lesions in misregistered regions were analyzed in this study. End-inspiration (EI) and EE PET data were derived from -10% to 15% and 30% to 80% of the breathing cycle, respectively. DIR was used to estimate a motion model from the EE to EI phase of the PET data. The model was then used to generate PET images at any phase of up to four times the amplitude of motion between EE and EI for correlation with the misregistered FB CT. Once a matched phase of the FB CT was determined, FB CT was deformed to a pseudo CT at the EE phase (DIR CT). DIR CT was compared with the ground truth DDG CT for AC and localization of the DDG PET. Between DDG PET/FB CT and DDG PET/DIR CT, a significant increase in ∆%SUV was observed (p<0.01), with median values elevating from 26.7% to 42.4%. This new method was most effective for lesions ≤3cm proximal to the diaphragm (p<0.001) but showed decreasing efficacy as the distance increased. When FB CT was severely misregistered with DDG PET (>3cm), DDG PET/DIR CT outperformed DDG PET/FB CT alone (p<0.05). Even when patients showed varied breathing patterns during the PET/CT scan, DDG PET/DIR CT still surpassed the efficiency of DDG PET/FB CT (p<0.01). Though DDG PET/DIR CT couldn't match the performance of the DDG PET/CT ground truth (42.4%vs. 53.6%, p<0.01), it reached 84% of its quantification, demonstrating good agreement and a strong overall correlation (regression coefficient of 0.94, p<0.0001). In some cases, anatomical distortion and blurring, and misregistration error were observed in DIR CT, rendering it still unable to correct inaccurate localization near the boundaries of two organs. Based on the motion model derived from gated PET data, DIR CT can significantly improve the quantification and localization of DDG PET. This approach can achieve a performance level of about 84% of the ground truth established by DDG PET/CT. These results show that self-gated PET and DIR CT may offer an alternative clinical solution to DDG PET and FB CT for quantification without the need for additional cine-CT imaging. DIR CT was at times inferior to DDG CT due to some distortion and blurring of anatomy and misregistration error.

A three‐dimensional (3D) optical flow program that includes a multi‐resolution feature has been developed and applied to 3D anatomic structure and gross tumor volume (GTV) contour mapping for four‐dimensional computed tomography (4D CT) data. The present study includes contour mapping for actual CT data sets from 3 patients and also for a thoracic phantom in which the displacement for each voxel was known. Of the CT data sets for the actual patients, one set was used to map lung and GTV contours over all respiration phases, and the other two were studied using only the end inspiration and end expiration phases, in which the displacements between phases were the largest. Including the residual motion in the 4D CT data and motion from table shaking, the optical flow calculation agrees with the known displacement to within 1 mm. Excluding errors not introduced by the optical flow algorithm, agreement for a displacement magnitude of 24 mm can be within 0.1 mm. The mapped contours in 4D CT images of lungs, liver, esophagus, GTV, and other structures for actual patients were acceptable to clinicians. The 3D optical flow program is a good tool for contour mapping of anatomic structure and tumor volume across 4D CT scans.PACS numbers: 87.55.D‐, 87.59.bd

Comparison of the Dosimetry of Spinal Fields in Craniospinal Irradiation using Two Dimensional, Three Dimensional and Intensity Modulated Radiation Therapy Planning Techniques

Purpose: In this study, we developed and evaluated a method for predicting lung surface deformation vector fields (SDVFs) based on surrogate signals such as chest and abdomen motion at selected locations and spirometry measurements. Methods: A Patient-specific 3D triangular surface mesh of the lung region at end-expiration (EE) phase was obtained by threshold-based segmentation method. For each patient, a spirometer recorded the flow volume changes of the lungs; and 192 selected points at a regular spacing of 2cm X 2cm matrix points over a total area of 34cm X 24cm on the surface of chest and abdomen was used to detect chest wall motions. Preprocessing techniques such as QR factorization with column pivoting (QRCP) were employed to remove redundant observations of the chest and abdominal area. To create a statistical model between the lung surface and the corresponding surrogate signals, we developed a predictive model based on canonical ridge regression (CRR). Two unique weighting vectors were selected for each vertex on the surface of the lung, and they were optimized during the training process using the all other phases of 4D-CT except the end-inspiration (EI) phase. These parameters were employed to predict the vertices locations of a testing data set, which was the EI phase of 4D-CT. Results: For ten lung cancer patients, the deformation vector field of each vertex of lung surface mesh was estimated from the external motion at selected positions on the chest wall surface plus spirometry measurements. The average estimation of 98th percentile of error was less than 1 mm (AP= 0.85, RL= 0.61, and SI= 0.82). Conclusion: The developed predictive model provides a non-invasive approach to derive lung boundary condition. Together with personalized biomechanical respiration modelling, the proposed model can be used to derive the lung tumor motion during radiation therapy accurately from non-invasive measurements.

Objective To explore the correlation between the respiration-induced clinical target volume (CTV) motion and volume variation and the dosimetric variation of planning target volume (PTV) and organs at risk (OAR) during free-breathing (FB) with whole breast intensity-modulated radiotherapy (IMRT).Methods Seventeen patients with breast conserving surgery underwent respiration-synchronized four-dimentional computed tomography (4DCT) simulation scans on the state of FB.The treatment plan was constructed using the end-inspiration phase scan,then copied and applied to the other respiratory phases.The dose distribution was calculated separately to evaluate the dose-volume histograms parameters for the PTV,ipsilateral lung and heart.Results During FB,the CTV motion vector was (2.09 ±0.74) mm,and the volume variation was (3.05 ± 0.94) ％.There was no correlation between the volume variation of CTV and dosimetric variation of PTV/OAR ( r =-0.390 -0.480,P =0.182 -0.775 ).In anteroposterior (AP),superoinferior (SI) and vector directions,the CTV movement correlated well with the PTV mean dose,conformal index,and the lung volume receiving high dose (V20,V30,V40,and V50;r=-0.975-0.791,P =0.000 -0.041 ).In SI and vector directions,the CTV displacement only correlated with the heart volume receiving ＞ 5 Gy ( V5 ) ( r =-0.795,0.687,P =0.006,0.028 ).The lung volume variation and the lung volume receiving high dose correlated reasonably well (r=0.655 -0.882,P=0.001-0.04 0).The heart volume variation only correlated with the V5 of heart (r =-0.701,P =0.024).Conclusions During free-breathing,the effect of breast volume variation can be ignored for whole breast IMRT,and whole breast IMRT assisted with breath-hold may improve the accuracy of dose delivery during radiotherapy. Key words: Radiotherapy,whole breast; Radiotherapy,intensity-modulated; Dosimetry