Is abdominal compression useful in lung stereotactic body radiation therapy? A 4DCT and dosimetric lobe-dependent study

PurposeTo determine the usefulness of abdominal compression in lung stereotactic body radiation therapy (SBRT) depending on lobe tumor location.Materials and methodsTwenty-seven non-small cell lung cancer patients were immobilized in the Stereotactic Body Frame? (Elekta). Eighteen tumors were located in an upper lobe, one in the middle lobe and nine in a lower lobe (one patient had two lesions). All patients underwent two four-dimensional computed tomography (4DCT) scans, with and without abdominal compression. Three-dimensional tumor motion amplitude was determined using manual landmark annotation. We also determined the internal target volume (ITV) and the influence of abdominal compression on lung dose-volume histograms.ResultsThe mean reduction of tumor motion amplitude was 3.5 mm (p = 0.009) for lower lobe tumors and 0.8 mm (p = 0.026) for upper/middle lobe locations. Compression increased tumor motion in 5 cases. Mean ITV reduction was 3.6 cm³ (p = 0.039) for lower lobe and 0.2 cm³ (p = 0.048) for upper/middle lobe lesions. Dosimetric gain of the compression for lung sparing was not clinically relevant.ConclusionsThe most significant impact of abdominal compression was obtained in patients with lower lobe tumors. However, minor or negative effects of compression were reported for other patients and lung sparing was not substantially improved. At our institute, patients with upper or middle lobe lesions are now systematically treated without compression and the usefulness of compression for lower lobe tumors is evaluated on an individual basis.     

Application of discrete cosine transform to assess the effect of tumor motion variations on the definition of ITV in lung and liver SBRT

PurposeTo use Discrete Cosine Transform to include tumor motion variations on ITV definition of SBRT patients.MethodsData from 66 patients was collected. 2D planar fluoroscopy images (FI) were available for 54 patients. Daily CBCT projections (CBCTp) from 29 patients were employed to measure interfraction amplitude variability. Systematic amplitude variations were obtained from 17 patients with data from both FI and CBCTp.Tumor motion curves obtained from FI were characterized with a Cosine model (CM), based on cosine functions to the power of 2, 4 or 6, and DCT. Performance of both models was evaluated by means of R² coefficient and by comparing their results on Internal Target Volume (ITV) margins against those calculated from original tumor motion curves.Amplitude variations from CBCTp, as well as estimations of baseline shift variations were added to the DCT model to account for their effect on ITV margins.ResultsDCT replicated tumor motion curves with a mean R² values for all patients of 0.86, 0.91 and 0.96 for the lateral (LAT), anterior-posterior (AP) and cranio-caudal (CC) directions respectively. CM yielded worst results, with R² values of 0.64, 0.61 and 0.74 in the three directions.Interfraction amplitude variation increased ITV margins by a 9%, while baseline shift variability implied a 40% and 80–100% increase for normalized values of baseline shift of 0.2 and 0.4 respectively.ConclusionsProbability distribution functions of tumor positions can be successfully characterized with DCT. This permits to include tumor motion variablilities obtained from patient population into patient specific ITVs.     

Tracking,gating, free-breathing,which technique to use for lung stereotactic treatments? A dosimetric comparison

BackgroundThe management of breath-induced tumor motion is a major challenge for lung stereotactic body radiation therapy (SBRT). Three techniques are currently available for these treatments: tracking (T), gating (G) and free-breathing (FB).AimTo evaluate the dosimetric differences between these three treatment techniques for lung SBRT.Materials and methodsPretreatment 4DCT data were acquired for 10 patients and sorted into 10 phases of a breathing cycle, such as 0% and 50% phases defined respectively as the inhalation and exhalation maximum. GTV_ph, PTV_ph (=GTV_ph + 3 mm) and the ipsilateral lung were contoured on each phase.For the tracking technique, 9 fixed fields were adjusted to each PTV_ph for the 10 phases. The gating technique was studied with 3 exhalation phases (40%, 50% and 60%). For the free-breathing technique, ITV_FB was created from a sum of all GTV_ph and a 3 mm margin was added to define a PTV_FB. Fields were adjusted to PTV_FB and dose distributions were calculated on the average intensity projection (AIP) CT. Then, the beam arrangement with the same monitor units was planned on each CT phase.The 3 modalities were evaluated using DVHs of each GTV_ph, the homogeneity index and the volume of the ipsilateral lung receiving 20 Gy (V_20Gy).ResultsThe FB system improved the target coverage by increasing D_mean (75.87_(T)–76.08_(G)–77.49_(FB)Gy). Target coverage was slightly more homogeneous, too (HI: 0.17_{(T and G)}–0.15_(FB)). But the lung was better protected with the tracking system (V_20Gy: 3.82_(T)–4.96_(G)–6.34_(FB)%).ConclusionsEvery technique provides plans with a good target coverage and lung protection. While irradiation with free-breathing increases doses to GTV, irradiation with the tracking technique spares better the lung but can dramatically increase the treatment complexity.     

Evaluation of target volume and dose accuracy in intrafractional cases of lung cancer based on 4D-CT and 4D-CBCT images using an in-house dynamic thorax phantom

BackgroundThis study aimed to evaluate the target volume and dose accuracy in intrafraction cases using 4-dimensional imaging modalities and an in-house dynamic thorax phantom. Intrafraction motion can create errors in the definition of target volumes, which can significantly affect the accuracy of radiation delivery. Motion management using 4-dimensional modalities is required to reduce the risk.Materials and methodsTwo variations in both breathing amplitude and target size were applied in this study. From these variations, internal target volume (ITVs) contoured in 10 phases of 4D-CT (ITV₁₀), average intensity projection (AIP), and mid-ventilation (Mid-V) images were reconstructed from all 4D-CT datasets as reference images. Free-breathing (FB), augmentation free-breathing (Aug-FB), and static images were also acquired using the 3D-CT protocol for comparisons. In dose evaluations, the 4D-CBCT modality was applied before irradiation to obtain position correction. Then, the dose was evaluated with Gafchromic film EBT3.ResultsThe ITV₁₀, AIP, and Mid-V provide GTVs that match the static GTV. The AIP and Mid-V reference images allowed reductions in ITVs and PTVs without reducing the range of target movement areas compared to FB and Aug-FB images with varying percentages in the range of 29.17% to 48.70%. In the dose evaluation, the largest discrepancies between the measured and planned doses were 10.39% for the FB images and 9.21% for the Aug-FB images.ConclusionThe 4D-CT modality can enable accurate definition of the target volume and reduce the PTV. Furthermore, 4D-CBCT provides localization images during registration to facilitate position correction and accurate dose delivery.     

Respiratory motion of adrenal gland metastases: Analyses using four-dimensional computed tomography images

PurposeTo evaluate the respiratory motion of adrenal gland metastases in three-dimensional directions using four-dimensional computed tomography (4DCT) images.MethodsFrom January 2013 to May 2016, 12 patients with adrenal gland metastases were included in this study. They all underwent 4DCT scans to assess respiratory motion of adrenal gland metastases in free breathing state. The 4DCT images were sorted into 10 image series according to the respiratory phase from the end inspiration to the end expiration, and then transferred to FocalSim workstation. All gross tumor volumes (GTVs) of adrenal gland metastases were drawn by a single physician and confirmed by a second. Relative coordinates of adrenal gland metastases were automatically generated to calculate adrenal gland metastases motion in different axial directions.ResultsThe average respiratory motion of adrenal gland metastases in left-right (LR), cranial-caudal (CC), anterior-posterior (AP), 3-dimensional (3D) vector directions was 3.4 ± 2.2 mm, 9.5 ± 5.5 mm, 3.8 ± 2.0 mm and 11.3 ± 5.3 mm, respectively. The ratios were 58.6% ± 11.4% and 63.2% ± 12.5% when the volumes of GTV_In0% and GTV _In100% were compared with volume of IGTV_10phase. The volume ratio of IGTV_10phase to GTV_3D was 1.73 ± 0.48.ConclusionsAdrenal gland metastasis is a respiration-induced moving target, and an internal target volume boundary should be provided when designing the treatment plan. The CC motion of adrenal gland metastasis is predominant and >5 mm, thus motion management strategies are recommended for patients undergoing external radiotherapy for adrenal gland metastasis.     

Evaluation of the target dose coverage of stereotactic body radiotherapy for lung cancer using helical tomotherapy: A dynamic phantom study

AimTo evaluate the target dose coverage for lung stereotactic body radiotherapy (SBRT) using helical tomotherapy (HT) with the internal tumor volume (ITV) margin settings adjusted according to the degree of tumor motion.BackgroundLung SBRT with HT may cause a dosimetric error when the target motion is large.Materials and methodsTwo lung SBRT plans were created using a tomotherapy planning station. Using these original plans, five plans with different ITV margins (4.0–20.0 mm for superior-inferior [SI] dimension) were generated. To evaluate the effects of respiratory motion on HT, an original dynamic motion phantom was developed. The respiratory wave of a healthy volunteer was used for dynamic motion as the typical tumor respiratory motion. Five patterns of motion amplitude that corresponded to five ITV margin sizes and three breathing cycles of 7, 14, and 28 breaths per minute were used. We evaluated the target dose change between a static delivery and a dynamic delivery with each motion pattern.ResultsThe target dose difference increased as the tumor size decreased and as the tumor motion increased. Although a target dose difference of <5 % was observed at ≤10 mm of tumor motion for each condition, a maximum difference of -9.94 % ± 7.10 % was observed in cases of small tumors with 20 mm of tumor motion under slow respiration.ConclusionsMinimizing respiratory movement is recommended as much as possible for lung SBRT with HT, especially for cases involving small tumors.     

Perturbation analysis of 4D dose distribution for scanned carbon-ion beam radiotherapy

PurposeTo evaluate the patients’ set-up error-induced perturbation effects on 4D dose distributions (4DDD) of range-adapted internal target volume-based (raITV) treatment plan using lung and liver 4DCT data sets.MethodsWe enrolled 20 patients with lung and liver cancer treated with respiratory-gated carbon-ion beam scanning therapy. PTVs were generated by adding a 2 mm range-adapted set-up margin on the raITVs. Set-up errors were simulated by shifting the beam isocenter in three translational directions of ±2 mm, ±4 mm, and ±6 mm. 4DDDs were calculated for both nominal and isocenter-shifted situations. Dose metrics of CTV dose coverage (D95) and normal tissue sparing were evaluated. Statistical significance with p < 0.01 was considered by Wilcoxon signed rank test.ResultsThe CTV dose coverage was more sensitive to set-up errors for lung cases than for liver cases, and more serious in superior-inferior direction. The sufficient CTV-D95 > 98% could be achieved with set-up errors less than ±2 mm in all shift directions both for lung and liver cases. With the increase of set-up error, the CTV dose coverage decreased gradually. The clinical criterial of CTV-D95 > 95% could not be fulfilled with set-up error reached to ±4 mm for lung cases, and ±6 mm for liver cases. OAR doses did not have a significant difference with each set-up error for both lung and liver cases.ConclusionsThe range-adapted set-up margin successfully prevented dose degradation of 4DDDs in the presence of the same magnitude of set-up error for raITV-based carbon-ion beam scanning therapy.     

Gated carbon-ion scanning treatment for pancreatic tumour with field specific target volume and organs at risk

ObjectiveTo assess the feasibility of treatment planning for pancreatic tumours subject to respiratory motion using field-specific target volumes (FTV) and field-specific organs at risk (FOAR) using four-dimensional computed tomography (4DCT).MethodsFourteen pancreatic cancer patients underwent 4DCT. Radiation oncologists contoured the gross tumour volume (GTV), clinical target volume (CTV), spinal cord, duodenum, kidneys, and stomach. The gating duty cycle was set to 30 % around exhalation. FTV and FOAR were calculated using the 4DCT dataset. Planning target volumes (PTV) and planning organs at risk volumes (PRV) were defined as equal to FTV and FOAR, respectively. A dose of 55.2 Gy relative biological effectiveness (RBE) was planned to target the PTV from four beam angles. A single field uniform dose (SFUD) plan was selected. The dose distribution, including intrafractional motion changes, was generated.ResultsThe mean volume of target receiving 95 % of the planned doses was 96.4 ± 4.1 % to the GTV and 94.7 ± 0.9 % to the CTV. The highest dose to 2 cc of duodenal volume was 27.5 Gy (RBE). The volume of the stomach receiving ⩾30 Gy (RBE) was <7.0 cc in all patients. All metrics for OARs satisfied dose constraints.ConclusionDose to the CTV was covered sufficiently by the 4DCT-generated FTV, and dose to OARs was reduced by 4DCT-generated FOAR. This methodology may prevent adverse reactions while preserving local tumour control.     

Irregular breathing during 4DCT scanning of lung cancer patients: Is the midventilation approach robust?

BackgroundWith 4DCT the risk of introducing positional systematic errors in lung cancer radiotherapy can be minimised. A common approach is to plan on the phase bin of the 4DCT best representing the tumour's time-weighted mean position also called the midventilation scan. However breathing irregularities can introduce uncertainties and potentially misrepresent both the tumour trajectory and the determination of the midventilation phase. In this study we evaluated the robustness of the midventilation approach in the presence of irregular breathing patterns.MethodsA LEGO Mindstorms^® phantom with compact balls simulating lung tumours was constructed. The breathing curves loaded in the phantom were either acquired from a human volunteer or constructed with various magnitudes (ranging from 12 to 29 mm) as well as various irregularities of motion pattern. Repeated 4DCT scans were performed while tumour trajectories were recorded with two motion tracking systems.ResultsThe time-weighted mean tumour position is accurately represented in 4DCT scans, even for irregular breathing patterns: the position presentation in the midventilation scan was always within in one standard deviation of the global position presentation (3 mm and 2 mm for regular and irregular breathing patterns, respectively). The displacement representation tended to be underestimated in 4DCT scans.ConclusionThe midventilation approach is robust even in the presence of breathing irregularity. The representation of the tumour trajectory in 4DCT scans is affected by breathing irregularity and the extent of tumour motion can be underestimated, which will affect the calculation of patient-individualised margins based on the 4DCT scan.     

Dose warping performance in deformable image registration in lung

PurposeIt is unclear that spatial accuracy can reflect the impact of deformed dose distribution. In this study, we used dosimetric parameters to compare an in-house deformable image registration (DIR) system using NiftyReg, with two commercially available systems, MIM Maestro (MIM) and Velocity AI (Velocity).MethodsFor 19 non-small-cell lung cancer patients, the peak inspiration (0%)-4DCT images were deformed to the peak expiration (50%)-4DCT images using each of the three DIR systems, which included computation of the deformation vector fields (DVF). The 0%-gross tumor volume (GTV) and the 0%-dose distribution were also then deformed using the DVFs. The agreement in the dose distributions for the GTVs was evaluated using generalized equivalent uniform dose (gEUD), mean dose (D_mean), and three-dimensional (3D) gamma index (criteria: 3 mm/3%). Additionally, a Dice similarity coefficient (DSC) was used to measure the similarity of the GTV volumes.ResultsD_mean and gEUD demonstrated good agreement between the original and deformed dose distributions (differences were generally less than 3%) in 17 of the patients. In two other patients, the Velocity system resulted in differences in gEUD of 50.1% and 29.7% and in D_mean of 11.8% and 4.78%. The gamma index comparison showed statistically significant differences for the in-house DIR vs. MIM, and MIM vs. Velocity.ConclusionsThe finely tuned in-house DIR system could achieve similar spatial and dose accuracy to the commercial systems. Care must be taken, as we found errors of more than 5% for D_mean and 30% for gEUD, even with a commercially available DIR tool.     

Occurrence of Fumonisin B<Subscript>1</Subscript> in Corn from the Main Corn-Producing Areas of China

Fumonisin B₁ (FB₁) is the most abundant of the fumonisin mycotoxins, mainly produced in maize by F. verticillioides and F. proliferatum. A total of 282 corn samples harvested in 2005 from six provinces, the main corn-producing areas of China, were analyzed for FB₁ using high-performance liquid chromatography. All samples except one were (99.6%) positive for FB₁ at levels varying from 3 to 71,121 ng/g with mean and median levels for all samples of 6,662 and 1,569 ng/g, respectively. During an analysis of the distribution pattern for FB₁, it became apparent that 43.6% of tested samples had FB₁ concentrations below 1,000 ng/g, while 25.2% contained in excess of 5,000 ng/g. The average exposure to FB₁ (1.1 μg/kg body weight/day) is within the provisional maximum tolerable daily intake of 2 μg/kg body weight/day set by the Joint FAO/WHO Expert Committee on Food Additives.     

Simulated four-dimensional CT for markerless tumor tracking using a deep learning network with multi-task learning

IntroductionOur markerless tumor tracking algorithm requires 4DCT data to train models. 4DCT cannot be used for markerless tracking for respiratory-gated treatment due to inaccuracies and a high radiation dose. We developed a deep neural network (DNN) to generate 4DCT from 3DCT data.MethodsWe used 2420 thoracic 4DCT datasets from 436 patients to train a DNN, designed to export 9 deformation vector fields (each field representing one-ninth of the respiratory cycle) from each CT dataset based on a 3D convolutional autoencoder with shortcut connections using deformable image registration. Then 3DCT data at exhale were transformed using the predicted deformation vector fields to obtain simulated 4DCT data. We compared markerless tracking accuracy between original and simulated 4DCT datasets for 20 patients. Our tracking algorithm used a machine learning approach with patient-specific model parameters. For the training stage, a pair of digitally reconstructed radiography images was generated using 4DCT for each patient. For the prediction stage, the tracking algorithm calculated tumor position using incoming fluoroscopic image data.ResultsDiaphragmatic displacement averaged over 40 cases for the original 4DCT were slightly higher (<1.3 mm) than those for the simulated 4DCT. Tracking positional errors (95th percentile of the absolute value of displacement, “simulated 4DCT” minus “original 4DCT”) averaged over the 20 cases were 0.56 mm, 0.65 mm, and 0.96 mm in the X, Y and Z directions, respectively.ConclusionsWe developed a DNN to generate simulated 4DCT data that are useful for markerless tumor tracking when original 4DCT is not available. Using this DNN would accelerate markerless tumor tracking and increase treatment accuracy in thoracoabdominal treatment.     

Retrospective assessment of a single fiducial marker tracking regimen with robotic stereotactic body radiation therapy for liver tumours

AimTo investigate tumour motion tracking uncertainties in the CyberKnife Synchrony system with single fiducial marker in liver tumours.BackgroundIn the fiducial-based CyberKnife real-time tumour motion tracking system, multiple fiducial markers are generally used to enable translation and rotation corrections during tracking. However, sometimes a single fiducial marker is employed when rotation corrections are not estimated during treatment.Materials and methodsData were analysed for 32 patients with liver tumours where one fiducial marker was implanted. Four-dimensional computed tomography (CT) scans were performed to determine the internal target volume (ITV). Before the first treatment fraction, the CT scans were repeated and the marker migration was determined. Log files generated by the Synchrony system were obtained after each treatment and the correlation model errors were calculated. Intra-fractional spine rotations were examined on the spine alignment images before and after each treatment.ResultsThe mean (standard deviation) ITV margin was 4.1 (2.3) mm, which correlated weakly with the distance between the fiducial marker and the tumour. The mean migration distance of the marker was 1.5 (0.7) mm. The overall mean correlation model error was 1.03 (0.37) mm in the radial direction. The overall mean spine rotations were 0.27° (0.31), 0.25° (0.22), and 0.23° (0.26) for roll, pitch, and yaw, respectively. The treatment time was moderately associated with the correlation model errors and weakly related to spine rotation in the roll and yaw planes.ConclusionsMore caution and an additional safety margins are required when tracking a single fiducial marker.     

Dosimetric impact of 4DCT artifact in carbon-ion scanning beam treatment: Worst case analysis in lung and liver treatments

IntroductionWe evaluated the impact of 4DCT artifacts on carbon-ion pencil beam scanning dose distributions in lung and liver treatment.Methods & materials4DCT was performed in 20 liver and lung patients using area-detector CT (original 4DCT). 4DCT acquisition by multi-detector row CT was simulated using original 4DCT by selecting other phases randomly (plus/minus 20% phases). Since tumor position can move over the respiratory range in original 4DCT, mid-exhalation was set as reference phase. Total prescribed dose of 60 Gy (RBE) was delivered to the clinical target volume (CTV). Reference dose distribution was calculated with the original CT, and actual dose distributions were calculated with treatment planning parameters optimized using the simulated CT (simulated dose). Dose distribution was calculated by substituting these parameters into the original CT.ResultsFor liver cases, CTV-D95 and CTV-Dmin values for the reference dose were 97.6 ± 0.5% and 89.8 ± 0.6% of prescribed dose, respectively. Values for the simulated dose were significantly degraded, to 88.6 ± 14.0% and 46.3 ± 26.7%, respectively. Dose assessment results for lung cases were 84.8 ± 12.8% and 58.0 ± 24.5% for the simulated dose, showing significant degradation over the reference dose of 95.1 ± 1.5% and 87.0 ± 2.2%, respectively.Conclusions4DCT image quality should be closely checked to minimize degradation of dose conformation due to 4DCT artifacts. Medical staff should pay particular attention to checking the quality of 4DCT images as a function of respiratory phase, because it is difficult to recognize 4DCT artifact on a single phase in some cases     

Dose delivery accuracy on helical tomotherapy for 4-dimensional tumor motion — a phantom study

BackgroundThe advances in image guidance and capability of highly conformal dose deliveries made possible the use of helical tomotherapy (HT) for lung cancer treatment. To determine the effect of respiratory motion on the delivered dose in HT, film dosimetry using a dynamic phantom was performed. This was a phantom study to determine the effect of motion on the delivered dose in HT.Materials and methods4D computed tomography (4DCT) was acquired for various target motions of CIRS dynamic phantom (CIRS Inc., Norfolk, USA) with 2.5cm diameter spherical target of volume 8.2 cc moving in the COS⁴ motion pattern. AveIP images and treatment plans were generated in the HT planning system. Target excursions during treatment delivery were changed in the superior-inferior, anteroposterior and lateral directions. The breathing cycle time was varied from 4 to 5 sec. and also the delivery interruptions were introduced. A film was exposed for each delivery and gamma analysis was performed.ResultsThe gamma pass rate (GPR) with 3%, 2 mm criteria for the target motion in the S-I direction showed a significant reduction from 97.5% to 54.4% as the motion increased from 3 mm to 8 mm (p = 0.03). For the target motion in S-I = 8 mm, L-R = A-P = 3 mm, the percentage decrease in the GPR was 74% (p = 0.001) for three interruptions.ConclusionThe ITV based approach in HT is ideal for a shallow breathing situation when the tumor excursions were confined to 5 mm in the S-I and 3 mm in L-R and A-P directions.     

Sampling intraspecific variability in leaf functional traits: Practical suggestions to maximize collected information

The choice of the best sampling strategy to capture mean values of functional traits for a species/population, while maintaining information about traits’ variability and minimizing the sampling size and effort, is an open issue in functional trait ecology. Intraspecific variability (ITV) of functional traits strongly influences sampling size and effort. However, while adequate information is available about intraspecific variability between individuals (ITV_BI) and among populations (ITV_POP), relatively few studies have analyzed intraspecific variability within individuals (ITV_WI). Here, we provide an analysis of ITV_WI of two foliar traits, namely specific leaf area (SLA) and osmotic potential (π), in a population of Quercus ilex L. We assessed the baseline ITV_WI level of variation between the two traits and provided the minimum and optimal sampling size in order to take into account ITV_WI, comparing sampling optimization outputs with those previously proposed in the literature. Different factors accounted for different amount of variance of the two traits. SLA variance was mostly spread within individuals (43.4% of the total variance), while π variance was mainly spread between individuals (43.2%). Strategies that did not account for all the canopy strata produced mean values not representative of the sampled population. The minimum size to adequately capture the studied functional traits corresponded to 5 leaves taken randomly from 5 individuals, while the most accurate and feasible sampling size was 4 leaves taken randomly from 10 individuals. We demonstrate that the spatial structure of the canopy could significantly affect traits variability. Moreover, different strategies for different traits could be implemented during sampling surveys. We partially confirm sampling sizes previously proposed in the recent literature and encourage future analysis involving different traits.     

Translational and rotational localization errors in cone-beam CT based image-guided lung stereotactic radiotherapy

PurposeAccurate localization is crucial in delivering safe and effective stereotactic body radiation therapy (SBRT). The aim of this study was to analyse the accuracy of image-guidance using the cone-beam computed tomography (CBCT) of the VERO system in 57 patients treated for lung SBRT and to calculate the treatment margins.Materials and methodsThe internal target volume (ITV) was obtained by contouring the tumor on maximum and mean intensity projection CT images reconstructed from a respiration correlated 4D-CT. Translational and rotational tumor localization errors were identified by comparing the manual registration of the ITV to the motion-blurred tumor on the CBCT and they were corrected by means of the robotic couch and the ring rotation. A verification CBCT was acquired after correction in order to evaluate residual errors.ResultsThe mean 3D vector at initial set-up was 6.6 ± 2.3 mm, which was significantly reduced to 1.6 ± 0.8 mm after 6D automatic correction. 94% of the rotational errors were within 3°. The PTV margins used to compensate for residual tumor localization errors were 3.1, 3.5 and 3.3 mm in the LR, SI and AP directions, respectively.ConclusionsOn-line image guidance with the ITV–CBCT matching technique and automatic 6D correction of the VERO system allowed a very accurate tumor localization in lung SBRT.     

Life without tRNAArg–adenosine deaminase TadA: evolutionary consequences of decoding the four CGN codons as arginine in Mycoplasmas and other Mollicutes

In most bacteria, two tRNAs decode the four arginine CGN codons. One tRNA harboring a wobble inosine (tRNA^Arg_ICG) reads the CGU, CGC and CGA codons, whereas a second tRNA harboring a wobble cytidine (tRNA^Arg_CCG) reads the remaining CGG codon. The reduced genomes of Mycoplasmas and other Mollicutes lack the gene encoding tRNA^Arg_CCG. This raises the question of how these organisms decode CGG codons. Examination of 36 Mollicute genomes for genes encoding tRNA^Arg and the TadA enzyme, responsible for wobble inosine formation, suggested an evolutionary scenario where tadA gene mutations first occurred. This allowed the temporary accumulation of non-deaminated tRNA^Arg_ACG, capable of reading all CGN codons. This hypothesis was verified in Mycoplasma capricolum, which contains a small fraction of tRNA^Arg_ACG with a non-deaminated wobble adenosine. Subsets of Mollicutes continued to evolve by losing both the mutated tRNA^Arg_CCG and tadA, and then acquired a new tRNA^Arg_UCG. This permitted further tRNA^Arg_ACG mutations with tRNA^Arg_GCG or its disappearance, leaving a single tRNA^Arg_UCG to decode the four CGN codons. The key point of our model is that the A-to-I deamination activity had to be controlled before the loss of the tadA gene, allowing the stepwise evolution of Mollicutes toward an alternative decoding strategy.     

A quantitative evaluation of deformable image registration based on MV cone beam CT images: Impact of deformation magnitudes and image modalities

Background and purposeTo evaluate the impact of deformation magnitude and image modality on deformable-image-registration (DIR) accuracy using Halcyon megavoltage cone beam CT images (MVCBCT).Materials and methodsPlanning CT images of an anthropomorphic Head phantom were aligned rigidly with MVCBCT and re-sampled to achieve the same resolution, denoted as pCT. MVCBCT was warped with twenty simulated pre-known virtual deformation fields (T_i, i = 1–20) with increasing deformation magnitudes, yielding warped CBCT (wCBCT). The pCT and MVCBCT were registered to wCBCT respectively (Multi-modality and Uni-modality DIR), generating deformation vector fields V_i and V_i′ (i = 1–20). V_i and V_i′ were compared with T_i respectively to assess the DIR accuracy geometrically. In addition, V_i, T_i, and V_i′ were applied to pCT, generating deformed CT (dCT_i), ground-truth CT (G_i) and deformed CT′ (dCT_i′) respectively. The Hounsfield Unit (HU) on these virtual CT images were also compared.ResultsThe mean errors of vector displacement increased with the deformation magnitude. For deformation magnitudes between 2.82 mm and 7.71 mm, the errors of uni-modality DIR were 1.16 mm ~ 1.73 mm smaller than that of multi-modality (p = 0.0001, Wilcoxon signed rank test). DIR could reduce the maximum signed and absolute HU deviations from 70.8 HU to 11.4 HU and 208 HU to 46.2 HU respectively.ConclusionsAs deformation magnitude increases, DIR accuracy continues to deteriorate and uni-modality DIR consistently outperformed multi-modality DIR. DIR-based adaptive radiotherapy utilizing the noisy MVCBCT images is only conditionally applicable with caution.