Impact of Anatomical Position Errors on Dose Distribution in Head and Neck Radiotherapy and Robust Image Registration Against Anatomical Changes.

BACKGROUND/AIM: This study pursued two goals: Firstly, to search for anatomical structures strongly correlating with dose deterioration, and secondly to investigate the effectiveness of image registration focusing on critical anatomy by comparing it with a conventional method. The aim was to achieve robust image registration to correct for anatomical changes during treatment. PATIENTS AND METHODS: Twenty patients with head and neck cancer were enrolled, and 68 simulation computed tomography (CT) and rescan CT image sets were retrospectively analyzed. Forty volumetric-modulated arc therapy and intensity-modulated proton therapy plans were generated and recalculated according to the rescan CT to evaluate the dose effects of anatomical changes. Correlation coefficients were calculated for the relationships between the six-axis motion of the anatomy and the dose indices for the clinical target volume (CTV) and organs at risk. In the image registration, we compared a conventional method and target-based registration that limited the registration range to the CTV and vertebrae. RESULTS: The CTV coverage and spinal cord dose were correlated with the position error associated with the pitch and vertical position of the vertebrae, and the parotid gland and oral cavity dose were strongly correlated with the position error associated with the roll of the clivus and mandible. The target registration improved CTV coverage and suppressed the increase in dose to organs at risk compared with conventional methods. CONCLUSION: Monitoring vertebral alignment, the assessment and correction of positioning errors associated with the clivus and mandible position errors are important to ensure the quality of daily treatment. Target-based registration may allow for more robust image registration.

Dosimetric impact of tumor position displacements between photon and proton stereotactic body radiation therapy for lung cancer.

Purpose: To investigate the impact of tumor position displacements (TPDs) on tumor dose coverage in photon and proton stereotactic body radiation therapy (SBRT) treatments for lung cancer patients. Methods: From our institutional database of 2877 fractions from 770 lung cancer patients treated with photon SBRT in 2017-2021, 163 fractions from 88 patients with recorded iso-center shifts of >1.5 cm in any direction under kV-cone-beam CT guidance were identified. By double registrations with bony and tumor alignments, the difference between the iso-center shifts of these two alignments was categorized as TPDs. One fraction from each of 15 patients who had TPD magnitudes >3 mm were selected for this study. For each patient, one proton plan using intensity modulated proton therapy (IMPT) with robust optimization was generated retrospectively. All photon plans had V100%RX>99% of GTVs and V100%RX>98% of ITVs. Proton plans were evaluated with two worse-case scenario (voxelwise worst and worst scenario) using 5mm and 3.5% uncertainty to achieve the same planning goals as the corresponding photon plans. These two evaluation proton plans were named proton-1st and proton-2nd plans. The dosimetric effect of TPD was simulated by shifting tumor contours with the corresponding shift on patient specific planning CT and by recalculating the dose of the original plan. Results: The range of magnitude of TPDs was 3.58-28.71 mm. In photon plans, TPDs did not impact tumor dose coverage, still achieving V100%RX of the GTV≥99% and V100%RX of the ITV≥98%. In proton plans for patients with TPDs>10 mm, inadequate target dose coverage was observed. More specifically, 8 fractions of proton-1st plans and 4 fractions of proton-2nd had V100%RX of the GTV<99% and V100%RX of the ITV<98%. Conclusions: Adequate tumor dose coverage was achieved in photon SBRT for magnitude of TPDs up to 20 mm. TPDs had greater impact in proton SBRT and adaptive planning was needed when the magnitude of TPDs>10 mm to provide adequate tumor dose coverage.

Detection of anatomical changes using two-dimensional x-ray images for head and neck adaptive radiotherapy.

PURPOSE: To develop a system for detecting anatomical changes using two-dimensional (2D) x-ray images. METHODS: Ten patients with head and neck cancer were retrospectively analyzed using 2D x-ray and cone-beam computed tomography (CBCT) images. The 2D x-ray images were acquired daily, whereas the CBCT images were acquired weekly during the treatment period. The developed system imported the 2D x-ray images obtained on the initial treatment day and on another day, and thereafter converted them into the water equivalent thickness (WET) using the conversion table. The difference between the WET images for the first and other treatment days (ΔWET) was calculated as the quantitative value for anatomical changes and visualized to recognize the anatomical change location. We compared ΔWET and the difference in the lateral neck distance (ΔLND) on the corresponding CBCT images. ΔLND was used as the ground truth for anatomical changes. ΔWET and ΔLND were measured at the first cervical vertebra (C1) and the tumor center (TC). C1 and TC were selected to observe the volume changes in the parotid gland and tumor, respectively. Sensitivity and specificity were calculated to evaluate the performance of the 2D-WET system. The cut-off values of WET and LND were set to 2-10 mm. Furthermore, intensity-modulated proton therapy (IMPT) plans for six patients with rescan CT images were generated. The IMPT plans on the rescan CT images were compared to the original plans on simulation CT using the dosimetric parameters for the target and the organs at risk. RESULTS: The mean differences between ΔWET and ΔLND for C1 and TC were -0.62 ± 1.66 mm and -0.93 ± 1.28 mm (mean ± 1 SD), respectively. ΔWET in the proposed system was in good agreement with ΔLND using the CBCT images. In the sensitivity and specificity results for C1 and TC with cut-off values from 2 to 10 mm, the sensitivity was >85% for all cut-off values, while the specificity was >90% at 5-10 mm and <90% at less than 5 mm. The average ΔWET at the time of replanning was 12.8 mm which resulted in maximum dose increase in the spinal cord D1cc by 8.4 Gy, the parotid gland D50 by 26.6 Gy, and the oral cavity D50 by 23.2 Gy. CONCLUSIONS: We developed a new system for detecting anatomical changes using 2D x-ray images. The developed system with ΔWET showed an agreement with ΔLND at C1 and TC with an average difference of less than 1 mm. ΔWET detected anatomical changes with high sensitivity and specificity with a cut-off value of 5-10 mm. This system can monitor daily anatomical changes without causing high exposure to patients and requiring any inefficient work, and it can be applied to daily online adaptive proton beam therapy and triggered adaptive radiotherapy.

Anatomical Increased/Decreased Changes in the Brain Area Following Individuals with Chronic Traumatic Complete Thoracic Spinal Cord Injury.

OBJECTIVES: This study aimed to investigate anatomical changes in the brain following chronic complete traumatic thoracic spinal cord injury (ThSCI) using voxel-based morphometry (VBM). That is, it attempted to examine dynamic physical change following thoracic injury and the presence or absence of regions with decreased and increased changes in whole brain volume associated with change in the manner of how activities of daily living are performed. METHODS: Twelve individuals with chronic traumatic complete ThSCI (age; 21-63 years, American Spinal Injury Association Impairment Scale; grade C-D) participated in this study. VBM was used to investigate the regions with increased volume and decreased volume in the brain in comparison with healthy control individuals. RESULTS: Decreases in volume were noted in areas associated with motor and somatosensory functions, including the right paracentral lobule (PCL)-the primary motor sensory area for lower limbs, left dorsal premotor cortex, and left superior parietal lobule (SPL). Furthermore, increased gray matter volume was noted in the primary sensorimotor area for fingers and arms, as well as in higher sensory areas. CONCLUSIONS: Following SCI both regions with increased volume and regions with decreased volume were present in the brain in accordance with changes in physical function. Using longitudinal observation, anatomical changes in the brain may be used to determine the rehabilitation effect by comparing present cases with cases with cervical SCI or cases with incomplete palsy.

Trend analysis of the dosimetric impact of anatomical changes during proton therapy for maxillary sinus carcinoma.

PURPOSE: Anatomical changes, such as shrinkage and aeration, can affect dose distribution in proton therapy (PT) for maxillary sinus carcinoma (MSC). These changes can affect the dose to the target and organs at risk (OARs); however, when these changes occur during PT is unclear. This study aimed to investigate the dosimetric impact of anatomical changes during PT. MATERIALS AND METHODS: Fifteen patients with MSC were enrolled in this study. Initial PT plans were generated based on initial computed tomography (CT) images. Several repeat CT images were obtained to confirm anatomical changes during PT. Evaluation PT plans were generated by copying initial PT plans to repeat CT images. The dose differences of the target and OARs were evaluated by comparing both the plans. RESULTS: At 3-4 weeks after the initiation of PT, the target volume reduced by approximately 10% as compared with the initial volume. Consequently, the target volumes gradually varied until the end of treatment. The value of V95 (volume that received 95% of the prescription dose) in the clinical target volume of the evaluation PT plan was similar to that of the initial PT plan. However, the dose to OARs, such as the contralateral optic nerve, contralateral eyeball, brainstem, and optic chiasm, increased significantly from the middle to the later phases of the treatment course. In contrast, there was a slight dose difference in the ipsilateral optic apparatus. CONCLUSION: The trend analysis in this study showed that anatomical changes appeared 3-4 weeks after the start of PT, and the dose to the OARs tended to increase. Therefore, it is recommended to check the status of tumor 3-4 weeks after the start of treatment to avoid the deterioration of dose distribution due to these changes.

Physiological and morphoanatomical effects of glyphosate in Eugenia uniflora, a Brazilian plant species native to the Atlantic Forest biome.

The herbicide glyphosate can cause severe ecotoxicological effects on non-target organisms. Eugenia uniflora L. (Myrtaceae) is very important for in situ environmental biomonitoring due to its wide distribution in the Atlantic Forest biome. Thus, this study aimed to evaluate the response of E. uniflora leaves to glyphosate. Eight-month-old plants were exposed to an aerial application of the herbicide at concentrations of 0, 144, 432, 864, and 1440 g a. e. ha-1 (grams of acid equivalent per hectare). Evaluations were performed on the 12th day after the glyphosate application (DAA). An accumulation of shikimic acid in the leaves of E. uniflora was observed. Glyphosate altered the photosynthetic parameters of the treated plants, with a drastic decrease in the photosynthetic rate, stomatal conductance, transpiration, and pigment content. There was an increase in Ci/Ca, lipid peroxidation, and electrolyte extravasation levels. Glyphosate also promoted ultrastructural, anatomical and visible damage to the E. uniflora leaves. Our findings indicate that glyphosate is phytotoxic to the native species E. uniflora at the tested doses. The presence of visible damage suggests that E. uniflora has remarkable potential as a bioindicator of glyphosate in the environment, making it a possible species for future biomonitoring projects.

Robustness of daily dose for each beam angle and accumulated dose for inter-fractional anatomical changes in passive carbon-ion radiotherapy for pancreatic cancer: Bone matching versus tumor matching.

PURPOSE: We aimed to assess the robustness of accumulated dose distributions for inter-fractional changes in passive carbon-ion radiotherapy for pancreatic cancer. METHODS: Ninety-five daily CT image sets acquired after the treatment of eight patients with pancreatic cancer were used in this prospective study. Dose distributions with treatment beam fields were recalculated for bone matching (BM) and tumor matching (TM) positions on all daily CT images, the accumulated doses being calculated using deformable image registration methods. The prescribed dose was 55.2 Gy (relative biological effectiveness [RBE]) in 12 fractions. Dose volume parameters of V95 (%) for CTV and GTV, and D2cc (Gy(RBE)) for the stomach and duodenum were evaluated. RESULTS: The medians (range) of CTV V95 (%) were 91.9 (86.1-100.0), 80.5 (56.1-90.6), and 86.4 (72.5-96.5) for the Plan, accumulated with BM and TM, respectively; GTV values (%) were 98.0 (85.7-100.0), 93.3 (65.7-99.9), and 96.2 (84.8-100.0), respectively. There were significant differences between all combinations apart from the Plan and TM for both targets. The values of stomach D2cc (Gy(RBE)) were 36.0 (16.9-43.4), 36.7 (17.9-45.0), and 35.2 (16.8-43.5), respectively; duodenum values (Gy(RBE)) were 25.2 (21.3-40.3), 30.1 (23.3-48.6), and 28.3 (20.4-50.6), respectively. There was a significant difference between the Plan and BM for duodenum only. CONCLUSIONS: TM is recommended over BM because it can achieve higher target dose coverage than BM. Nevertheless, it is not enough in some cases. Further technical improvements are necessary to improve the target dose coverage.

Impact of Inter-fractional Anatomical Changes on Dose Distributions in Passive Carbon-Ion Radiotherapy for Prostate Cancer: Comparison of Vertical and Horizontal Fields.

Purpose: We quantified the inter-fractional changes associated with passive carbon-ion radiotherapy using vertical and horizontal beam fields for prostate cancer. Methods: In total, 118 treatment-room computed tomography (TRCT) image sets were acquired from 10 patients. Vertical (anterior-posterior) and horizontal (left-right) fields were generated on the planning target volume identified by treatment planning CT. The dose distribution for each field was recalculated on each TRCT image set at the bone-matching position and evaluated using the dose-volume parameters for the prostate and rectum V95 values. To confirm adequate margins, we generated vertical and horizontal fields with 0-, 2-, 4-, and 6-mm isotropic margins from the prostate and recalculated the dose distributions on all TRCT image sets. Sigmoid functions were fitted to a plot of acceptable ratios (that is, when prostate V95 > 98%) vs. the isotropic margin size to identify the margin at which this ratio was achieved in 95% of patients with a vertical or horizontal field. Results: The prostate V95 values (mean ± standard deviation) were 99.89 ± 0.62% and 99.99 ± 0.00% with vertical and horizontal fields, respectively; this difference was not statistically significant (p = 0.067). The rectum V95 values were 1.93 ± 1.25 and 1.88 ± 0.96 ml with vertical and horizontal fields, respectively; the difference was not statistically significant (p = 0.432). The estimated adequate margins were 2.2 and 3.0 mm for vertical and horizontal fields, respectively. Conclusions: Although there is no significant difference, horizontal fields offer higher reproducibility for prostate dosing than vertical fields in our clinical setting, and 3.0 mm was found to be an adequate margin for inter-fractional changes.

External validation of a hidden Markov model for gamma-based classification of anatomical changes in lung cancer patients using EPID dosimetry.

PURPOSE: To externally validate a hidden Markov model (HMM) for classifying gamma analysis results of in vivo electronic portal imaging device (EPID) measurements into different categories of anatomical change for lung cancer patients. Additionally, the relationship between HMM classification and deviations in dose-volume histogram (DVH) metrics was evaluated. METHODS: The HMM was developed at CHU de Québec (CHUQ), and trained on features extracted from gamma analysis maps of in vivo EPID measurements from 483 fractions (24 patients, treated with three-dimensional 3D-CRT or intensity modulated radiotherapy), using the EPID measurement of the first treatment fraction as reference. The model inputs were the average gamma value, standard deviation, and average value of the highest 1% of gamma values, all averaged over all beams in a fraction. The HMM classified each fraction into one of three categories: no anatomical change (Category 1), some anatomical change (no clinical action needed, Category 2) and severe anatomical change (clinical action needed, Category 3). The external validation dataset consisted of EPID measurements from 263 fractions of 30 patients treated at Maastro with volumetric modulated arc therapy (VMAT) or hybrid plans (containing both static beams and VMAT arcs). Gamma analysis features were extracted in the same way as in the CHUQ dataset, by using the EPID measurement of the first fraction as reference (γQ), and additionally by using an EPID dose prediction as reference (γM). For Maastro patients, cone beam computed tomography (CBCT) scans and image-guided radiotherapy (IGRT) classification of these images were available for each fraction. Contours were propagated from the planning CT to the CBCTs, and the dose was recalculated using a Monte Carlo dose engine. Dose-volume histogram metrics for targets and organs-at-risk (OARs: lungs, heart, mediastinum, spinal cord, brachial plexus) were extracted for each fraction, and compared to the planned dose. HMM classification of the external validation set was compared to threshold classification based on the average gamma value alone (a surrogate for clinical classification at CHUQ), IGRT classification as performed at Maastro, and differences in DVH metrics extracted from 3D dose recalculations on the CBCTs. RESULTS: The HMM achieved 65.4%/65.0% accuracy for γQ and γM, respectively, compared to average gamma threshold classification. When comparing HMM classification with IGRT classification, the overall accuracy was 29.7% for γQ and 23.2% for γM. Hence, HMM classification and IGRT classification of anatomical changes did not correspond. However, there is a trend towards higher deviations in DVH metrics with classification into higher categories by the HMM for large OARs (lungs, heart, mediastinum), but not for the targets and small OARs (spinal cord, brachial plexus). CONCLUSION: The external validation shows that transferring the HMM for anatomical change classification to a different center is challenging, but can still be valuable. The HMM trained at CHUQ cannot be used directly to classify anatomical changes in the Maastro data. However, it may be possible to use the model in a different capacity, as an indicator for changes in the 3D dose based on two-dimensional EPID measurements.

Endograft Conformability in Fenestrated Endovascular Aneurysm Repair for Complex Abdominal Aortic Aneurysms.

Purpose: To compare the impact of 2 commercially available custom-made fenestrated endografts on patient anatomy. Materials and Methods: The records of 234 patients who underwent fenestrated endovascular aneurysm repair for abdominal aortic aneurysm from March 2002 to July 2016 in 2 hospitals were screened to identify those who had pre- and postoperative computed tomography angiography assessments with a slice thickness of ≤2 mm. The search identified 145 patients for further analysis: 110 patients (mean age 72.4±7.1 years; 94 men) who had been treated with the Zenith Fenestrated (ZF) endograft and 35 patients (mean age 72.3±7.3 years; 30 men) treated with the Fenestrated Anaconda (FA) endograft. Measurements included aortic diameters at the level of the superior mesenteric artery (SMA) and renal arteries, target vessel angles, target vessel clock positions, and the target vessel tortuosity index. Variables were tested for inter- and intraobserver agreement. Results: There was a good agreement between observers in all tested variables. The native anatomy changed in both groups after endograft implantation. In the ZF group, changes were seen in the angles of the celiac artery (p=0.012), SMA (p=0.022), left renal artery (LRA) (p<0.001), and the right renal artery (RRA) (p<0.001); the aortic diameter at the SMA level (p<0.001); and the LRA (p<0.001) and RRA (p<0.001) clock positions. In the FA group, changes were seen in the angles of the LRA (p=0.001) and RRA (p<0.001) and in the SMA tortuosity index (p=0.044). Between group differences in changes were seen for the aortic diameters at the SMA and renal artery levels (p<0.001 for both) and the LRA clock position (p=0.019). Conclusion: Both custom-made fenestrated endografts altered vascular anatomy. The data suggest a higher conformability of the Fenestrated Anaconda endograft compared with the Zenith Fenestrated.

Comparison between bone matching and marker matching for evaluation of intra- and inter-fractional changes in accumulated dose of carbon ion radiotherapy for hepatocellular carcinoma.

BACKGROUND AND PURPOSE: To determine whether bone matching (BM) or marker matching (MM) is the better positioning technique for carbon ion radiotherapy (CIRT) of primary hepatocellular carcinoma (HCC), we prospectively evaluated accumulated dose distributions with respect to intra- and inter-fractional anatomical changes. MATERIALS AND METHODS: The accumulated doses in ten patients with HCC were evaluated, with the doses being calculated with respect to inter-fractional changes (InterDose) on treatment-room CT images on day 1 or day 2 of therapy (RefCT). This was accomplished by warping 3-day CT dose distributions to the RefCT through deformable registration. The accumulated doses were also calculated with respect to intra-fractional change (IntraDose) calculated by warping dose distributions for three 4DCT phases to the RefCT. Each dose was evaluated using dose-volume parameters for the clinical target volume (CTV) percentages receiving greater than 95% of the prescription dose (V95). RESULTS: The InterDose CTV V95 values (mean [range]) were BM: 98.74% (95.62-100%), MM: 99.79% (98.55-100%), and the IntraDose values were BM: 99.46% (98.10-100%), MM: 99.74% (98.91-100%). Although all cases were acceptable with either matching method, MM provided better values than BM. CONCLUSION: MM is a better positioning technique than BM for ensuring the target dose during and between fractions of CIRT. However, further analysis is required as our study included only a low number of cases.

Tinkering and the Origins of Heritable Anatomical Variation in Vertebrates.

Evolutionary change comes from natural and other forms of selection acting on existing anatomical and physiological variants. While much is known about selection, little is known about the details of how genetic mutation leads to the range of heritable anatomical variants that are present within any population. This paper takes a systems-based view to explore how genomic mutation in vertebrate genomes works its way upwards, though changes to proteins, protein networks, and cell phenotypes to produce variants in anatomical detail. The evidence used in this approach mainly derives from analysing anatomical change in adult vertebrates and the protein networks that drive tissue formation in embryos. The former indicate which processes drive variation-these are mainly patterning, timing, and growth-and the latter their molecular basis. The paper then examines the effects of mutation and genetic drift on these processes, the nature of the resulting heritable phenotypic variation within a population, and the experimental evidence on the speed with which new variants can appear under selection. The discussion considers whether this speed is adequate to explain the observed rate of evolutionary change or whether other non-canonical, adaptive mechanisms of heritable mutation are needed. The evidence to hand suggests that they are not, for vertebrate evolution at least.

Assessment of prior image induced nonlocal means regularization for low-dose CT reconstruction: Change in anatomy.

PURPOSE: Repeated computed tomography (CT) scans are prescribed for some clinical applications such as lung nodule surveillance. Several studies have demonstrated that incorporating a high-quality prior image into the reconstruction of subsequent low-dose CT (LDCT) acquisitions can either improve image quality or reduce data fidelity requirements. Our proposed previous normal-dose image induced nonlocal means (ndiNLM) regularization method for LDCT is an example of such a method. However, one major concern with prior image based methods is that they might produce false information when the prior image and the current LDCT image show different structures (for example, if a lung nodule emerges, grows, shrinks, or disappears over time). This study aims to assess the performance of the ndiNLM regularization method in situations with change in anatomy. METHOD: We incorporated the ndiNLM regularization into the statistical image reconstruction (SIR) framework for reconstruction of subsequent LDCT images. Because of its patch-based search mechanism, a rough registration between the prior image and the current LDCT image is adequate for the SIR-ndiNLM method. We assessed the performance of the SIR-ndiNLM method in lung nodule surveillance for two different scenarios: (a) the nodule was not found in a baseline exam but appears in a follow-up LDCT scan; (b) the nodule was present in a baseline exam but disappears in a follow-up LDCT scan. We further investigated the effect of nodule size on the performance of the SIR-ndiNLM method. RESULTS: We found that a relatively large search-window (e.g., 33 × 33) should be used for the SIR-ndiNLM method to account for misalignment between the prior image and the current LDCT image, and to ensure that enough similar patches can be found in the prior image. With proper selection of other parameters, experimental results with two patient datasets demonstrated that the SIR-ndiNLM method did not miss true nodules nor introduce false nodules in the lung nodule surveillance scenarios described above. We also found that the SIR-ndiNLM reconstruction shows improved image quality when the prior image is similar to the current LDCT image in anatomy. These gains in image quality might appear small upon visual inspection, but they can be detected using quantitative measures. Finally, the SIR-ndiNLM method also performed well in ultra-low-dose conditions and with different nodule sizes. CONCLUSIONS: This study assessed the performance of the SIR-ndiNLM method in situations in which the prior image and the current LDCT image show substantial anatomical differences, specifically, changes in lung nodules. The experimental results demonstrate that the SIR-ndiNLM method does not introduce false lung nodules nor miss true nodules, which relieves the concern that this method might produce false information. However, there is insufficient evidence that these findings will hold true for all kinds of anatomical changes.