Superior-inferior Direction Research Articles

Analysis of sagittal plane cine magnetic resonance imaging for measurement of pancreatic tumor residual motion during breath hold and evaluation of gating margins used in radiotherapy treatment.

In pancreatic radiotherapy, residual tumor motion during treatment increases the risk of toxicity. Cine imaging acquired during magnetic resonance guided radiotherapy (MRgRT) enables real-time treatment gating in response to anatomical motion, which can reduce this risk; however, treatment gating can negatively impact the efficiency of treatment. This study aimed to quantify the extent of residual tumor motion during breath hold and evaluate the appropriateness of the treatment gating margins used in current clinical practice. Cine imaging acquired during pancreatic MRgRT of 11 patients on the ViewRay MRIdian was analyzed. The total duration of treatment analyzed was 12 h 13 min. Improved methods for processing and analyzing cine imaging were developed: breath holds were systematically separated with frequency analysis, residual motion was measured with consideration of both the tracking structure contour and centroid, and residual motion measurements were supported by phantom measurements of image scaling, resolution, and noise. Residual motion was measured at angles 0°, 45°, 90°, and 135° to the superior-inferior (SI) direction. Total residual motion was measured by combining directional measurements. The minimum tracking structure displacement resolvable through cine imaging was found to be 1.5mm; therefore, residual motion analysis was limited to 1.5mm spatial resolution. Total residual motion was contained within margins ±1.5, ±3, and ±4.5mm with mean percentage frequencies of 97.0%, 91.1%, and 67.8%. Most residual motion was observed in the SI direction, and significantly more residual motion was measured for the tracking structure contour than the centroid. The results demonstrate that patients are largely able to maintain breath hold positions to within a 3mm margin, thus provide evidence that supports the use of a 3mm gating margin in clinical practice. Residual motion frequently exceeded 1.5mm so a reduction in gating margin would have an undesirable impact on treatment efficiency.

Patient-specific deep learning tracking framework for real-time 2D target localization in MRI-guided radiotherapy

Purpose: We propose a tumor tracking framework for 2D cine MRI based on a pair of deep learning (DL) models relying on patient-specific (PS) training.Methods and materials: The chosen DL models are: 1) an image registration transformer and 2) an auto-segmentation convolutional neural network (CNN). We collected over 1,400,000 cine MRI frames from 219 patients treated on a 0.35 T MRI-linac plus 7,500 frames from additional 35 patients which were manually labelled and subdivided into fine-tuning, validation, and testing sets. The transformer was first trained on the unlabeled data (without segmentations). We then continued training (with segmentations) either on the fine-tuning set or for PS models based on eight randomly selected frames from the first 5 s of each patient's cine MRI. The PS auto-segmentation CNN was trained from scratch with the same eight frames for each patient, without pre-training. Furthermore, we implemented B-spline image registration as a conventional model, as well as different baselines. Output segmentations of all models were compared on the testing set using the Dice similarity coefficient (DSC), the 50% and 95% Hausdorff distance (HD50%/HD95%), and the root-mean-square-error of the target centroid in superior-inferior direction (RMSESI).Results: The PS transformer and CNN significantly outperformed all other models, achieving a median (inter-quartile range) DSC of 0.92 (0.03)/0.90 (0.04), HD50% of 1.0 (0.1)/1.0 (0.4) mm, HD95% of 3.1 (1.9)/3.8 (2.0) mm and RMSESI of 0.7 (0.4)/0.9 (1.0) mm on the testing set. Their inference time was about 36/8 ms per frame and PS fine-tuning required 3 min for labelling and 8/4 min for training. The transformer was better than the CNN in 9/12 patients, the CNN better in 1/12 patients and the two PS models achieved the same performance on the remaining 2/12 testing patients.Conclusion: For targets in the thorax, abdomen and pelvis, we found two PS DL models to provide accurate real-time target localization during MRI-guided radiotherapy.

Intrafraction motion and impact of margin reduction for MR-Linac online adaptive radiotherapy for pancreatic cancer treatments.

Online adaptive radiotherapy is well suited for stereotactic ablative radiotherapy (SABR) in pancreatic cancer due to considerable intrafractional tumour motion. This study aimed to assess intrafraction motion and generate adjusted planning target volume (PTV) margins required for online adaptive radiotherapy in pancreatic cancer treatment using abdominal compression on the magnetic resonance linear accelerator (MR-Linac). Motion monitoring images obtained from 67 fractions for 15 previously treated pancreatic cancer patients were analysed. All patients received SABR (50 Gy in five fractions) on the MR-Linac using abdominal compression. The analysis included quantification of intrafraction motion, leading to the development of adjusted PTV margins. The dosimetric impact of implementing the adjusted PTV was then evaluated in a cohort of 20 patients. Intrafraction motion indicated an average target displacement of 1-3 mm, resulting in an adjusted PTV margin of 2 mm in the right-left and superior-inferior directions, and 3 mm in the anterior-posterior direction. Plans incorporating these adjusted margins consistently demonstrated improved dose to target volumes, with improvements averaging 1.5 Gy in CTV D99%, 4.9 Gy in PTV D99% and 1.2 Gy in PTV-high D90%, and better sparing of the organs at risk (OAR). The improved target volume coverage and reduced OAR dose suggest potential for reducing current clinical margins for MR-Linac treatment. However, it is important to note that decreasing margins may reduce safeguards against geographical misses. Nonetheless, the continued integration of gating systems on MR-Linacs could provide confidence in adopting reduced margins.

Investigation of pelvic floor influence on prostate displacement in image-guided radiotherapy.

The uncertainty of target location during prostate cancer radiotherapy plays an important role in accurate dose delivery and radiation toxicity in adjacent organs. This study analyzed displacement correlations between the prostate and pelvic floor. We retrospectively analyzed registration results from 467 daily cone-beam computed tomography (CT) in 12 patients with prostate cancer who received radiation therapy. We analyzed prostate displacement and the pelvic floor relative to the pelvic bone's anatomy in the translational and rotational directions and identified statistical correlations. The systematic (Σ) and random (σ) displacements of the prostate in the three translational directions, anterior-posterior (AP), superior-inferior (SI), and right-left (RL), were 1.49 ± 1.45, 2.10 ± 1.40, and 0.24 ± 0.53 mm, respectively, and in the rotational directions of the pitch, roll, and yaw were 2.10 ± 2.02°, 0.42 ± 0.74°, and 0.42 ± 0.64°, respectively. The pelvic floor displacements were 2.37 ± 1.96, 2.71 ± 2.28, and 0.47 ± 0.84 mm in the AP, SI, and RL directions, respectively, and 0.93 ± 1.49°, 0.98 ± 1.28 °, and 0.87 ± 0.94° in the pitch, roll, and yaw directions, respectively. Additionally, there were statistically significant correlations between the displacement of the prostate and pelvic floor in the AP and SI directions, with correlation coefficients (r) of 0.74 (p < 0.001) and 0.69 (p < 0.001), respectively. The movement of the pelvic floor may be an important factor that causes prostate displacement, affecting the accuracy of radiotherapy. Therefore, it is necessary to take appropriate measures to ensure that the pelvic floor muscle tension is as consistent as possible in the treatment' CT scan and daily treatment.

Vendor-Specific Correction Software for Apparent Diffusion Coefficient Bias Due to Gradient Nonlinearity in Breast Diffusion-Weighted Imaging Using Ice-Water Phantom.

This study aimed to evaluate a vendor-specific correction software for apparent diffusion coefficient (ADC) bias due to gradient nonlinearity in breast diffusion-weighted magnetic resonance imaging using an ice-water phantom. The phantom consists of 5 plastic tubes with a length of 100 mm and a diameter of 15 mm, filled with distilled water and immersed in an ice-water bath. Diffusion-weighted images were acquired by echo-planar imaging sequence on a 3.0-T scanner. ADC maps with and without correction were calculated using 4 b -values (0, 100, 600, and 800 s/mm 2 ). The mean ADCs were measured using a rectangular profile with 5 × 40 pixels in the anterior-posterior (AP) and a square region of interest with 5 × 5 pixels in the right-left (RL) and superior-inferior (SI) directions on the ADC map. ADC was compared with and without correction using a paired t test. Additionally, ADC of the ice-water phantom was measured at the magnet isocenter. ADC increased in the AP and RL directions and decreased in the SI direction with increasing distance from the isocenter before correction. After the correction, ADC at the off-center positions in the AP, RL, and SI directions was reduced to within 5% of the expected value. There were significant differences in the ADC at the off-center positions without and with correction ( P < 0.001); however, ADC at the magnet isocenter did not vary after correction (1.08 ± 0.02 × 10 -3 mm 2 /s). The vendor-specific software corrected the ADC bias due to gradient nonlinearity at the off-center positions in the AP, RL, and SI directions. Therefore, the software will contribute to the accurate ADC assessment in breast DWI.

Association Between Hip Translation and Hip Rotation and Anatomy: A Pilot Quasi-static MRI Study.

There is little known about translation of the hip and the relationship with hip rotation and morphology in asymptomatic patients. (1) Femoral head would exhibit significant translations in asymptomatic hips, (2) femoral head translations would correlate to femoral rotations, and (3) range of femoral head translations would correlate to hip morphology. Cross-sectional study; Level of evidence, 3. A total of 11 individuals (age, 23-47 years; 64% female) with asymptomatic hips underwent hip magnetic resonance imaging (MRI) in the following postures: neutral (supine), midflexion, maximum-flexion, internal rotation, internal rotation + midflexion, internal rotation + maximum-flexion, adduction, flexion-abduction-external rotation (FABER), extension, and lateral abduction. All rotations were passive. MRI-generated 3-dimensional hip models were used to quantify femoral rotations and translations. Femoral head diameter, acetabular diameter, lateral center-edge angle, alpha angle, femoral anteversion, acetabular version and inclination, and neck-shaft angle were measured from MRI. A t test was used if measured translations were statistically significant. Linear regression was used to assess the associations between translation and rotation. Pearson correlation was used to assess the relationships between hip anatomy and range of femoral head translations. In all tested positions, the femoral head translated anteriorly by 2 ± 1 mm (maximum 5 mm, P < .001), posteriorly by 1 ± 1 mm (maximum 6 mm, P < .001), superiorly by 2 ± 2 mm (maximum 7 mm, P < .001), inferiorly by 2 ± 2 mm (maximum 6 mm, P < .001), laterally by 1 ± 1 mm (maximum 4 mm, P < .001), and medially by 2 ± 1 mm (maximum 5 mm, P < .001), relative to the rested supine position. Femoral flexion was associated with posterior translation of the femoral head (P = .038). Femoral abduction was associated with medial translation of the femoral head (P = .042). Higher femoral anteversion and smaller alpha angle were associated with a higher total magnitude of femoral head translation in the anterior-posterior direction (P < .04). Smaller femoral anteversion, higher acetabular inclination, smaller lateral center-edge angle, and lower neck-shaft angle were associated with a higher total magnitude of femoral head translation in the superior-inferior direction (P ≤ .03). Our study demonstrated that, during passive physiologic movement, asymptomatic hips on average translated up to 2 mm (with up to 7 mm maximum translation in some positions), which is potentially related to hip rotations and morphology. Further investigations are warranted to understand the normal and pathologic hip translations and their impact on hip function (ie, instability and impingement).

Optimization of motion-corrected liver diffusion-weighted imaging at 3 Tesla (3T): incorporating complex averaging and reparametrized sinc fatsat pulse with optimized water excitation pulse.

In liver diffusion-weighted imaging (DWI), single-shot echo-planar imaging (SS-EPI) sequences are susceptible to motion artifacts, resulting in image blurring and decreased lesion detection rates. This study aimed to develop and optimize a motion-corrected (MOCO) technique for liver DWI at 3 Tesla (3T). The technique incorporates motion correction, complex averaging, and a combination of a reparametrized sinc fatsat pulse with an optimized water excitation pulse. This prospective cross-sectional study performed at Fujian Medical University Union Hospital included 42 healthy volunteers who underwent four SS-EPI DWI sequences on a 3T magnetic resonance imaging (MRI) system between January 2023 and March 2023. The sequences included a navigator-triggered (NT) MOCO-DWI, two free-breathing (FB) MOCO-DWI, and an FB conventional DWI (FB cDWI) sequence. Motion correction and complex averaging were performed for both MOCO-DWI sequences, and fat suppression was achieved using either a sinc fatsat pulse with optimized water excitation or a conventional spectral attenuated inversion recovery (SPAIR) pulse. Liver signal-to-noise ratio (SNR) was measured at b=1,000 s/mm2. Qualitative parameters were independently evaluated by three radiologists using 5-point Likert scales. Quantitative parameters were assessed using the Kolmogorov-Smirnov test, and variance homogeneity was assessed using Levene's test. Regarding the qualitative analysis, the Friedman test was used to compare subjective scores among the four techniques. The SNRs of the liver were significantly higher with FB MOCO-DWI compared to the other EPI DWI sequences at b=1,000 s/mm2 (P<0.05). In the superior-inferior direction, the SNRs of the inferior level of the liver were higher than those of the superior level in NT MOCO-DWI. The qualitative results showed significantly higher ratings for NT MOCO-DWI and FB MOCO-DWI compared to the other EPI DWI sequences at b=1,000 s/mm2 (P<0.05). Regarding the apparent diffusion coefficient (ADC) quantification, the ADC values of the left lobe were higher than those of the right lobe in all four techniques. The proposed EPI DWI technique, incorporating motion correction, complex averaging, and a modified fat suppression scheme using spectral fat saturation and binomial water excitation, was found to be clinically feasible for liver MRI. The FB MOCO-DWI sequence, with its superior SNR and excellent image quality, is recommended for liver DW imaging at 3T in clinical routine.

Application of motion prediction based on a long short-term memory network for imaging dose reduction in real-time tumor-tracking radiation therapy

PurposeTo demonstrate the possibility of using a lower imaging rate while maintaining acceptable accuracy by applying motion prediction to minimize the imaging dose in real-time image-guided radiation therapy. MethodsTime-series of three-dimensional internal marker positions obtained from 98 patients in liver stereotactic body radiation therapy were used to train and test the long-short-term memory (LSTM) network. For real-time imaging, the root mean squared error (RMSE) of the prediction on three-dimensional marker position made by LSTM, the residual motion of the target under respiratory-gated irradiation, and irradiation efficiency were evaluated. In the evaluation of the residual motion, the system-specific latency was assumed to be 100 ms. ResultsExcept for outliers in the superior–inferior (SI) direction, the median/maximum values of the RMSE for imaging rates of 7.5, 5.0, and 2.5 frames per second (fps) were 0.8/1.3, 0.9/1.6, and 1.2/2.4 mm, respectively. The median/maximum residual motion in the SI direction at an imaging rate of 15.0 fps without prediction of the marker position, which is a typical clinical setting, was 2.3/3.6 mm. For rates of 7.5, 5.0, and 2.5 fps with prediction, the corresponding values were 2.0/2.6, 2.2/3.3, and 2.4/3.9 mm, respectively. There was no significant difference between the irradiation efficiency with and that without prediction of the marker position. The geometrical accuracy at lower frame rates with prediction applied was superior or comparable to that at 15 fps without prediction. In comparison with the current clinical setting for real-time image-guided radiation therapy, which uses an imaging rate of 15.0 fps without prediction, it may be possible to reduce the imaging dose by half or more. ConclusionsMotion prediction can effectively lower the frame rate and minimize the imaging dose in real-time image-guided radiation therapy.

Analysis of intra-fractional positioning correction performed by cone beam computed tomography in SBRT treatments

PurposeThis study aims to evaluate the positioning correction extracted from Intra-fraction Cone Beam (IF-CBCT) images obtained during Stereotactic Body Radiotherapy (SBRT) treatments, and to assess whether its magnitude justifies its acquisition. In addition, the results obtained in lung, liver, and pancreas SBRTs with two deep inspiration breath-hold systems (DIBH), and for prostate with/without ultrasound (US) monitoring were compared. Methods1449 treatments, performed with two linear accelerators (LINACs) were retrospectively analyzed. DIBH were performed either with a spirometry-based device or a surface-guidance system and one LINAC was equipped with US monitoring system for prostate. Significance tests were used to account for differences between units. ResultsGroup systematic error (M) was approximately –0.7 mm for DIBH treatments in superior-inferior (SI) direction with no difference (p > 0.7) between LINACs. Moreover, there was a SI difference of 0.5 mm for prostate treatments (p = 0.008), in favor of the US monitored one. In anterior-posterior (AP) direction, only liver treatments exhibited differences between LINACs, with the spirometer-based system being 0.8 mm inferior (p = 0.003). M<0.4 mm in left–right (LR) direction was found for all locations and LINACs. The spirometer-based system resulted in lower standard deviation of systematic and random errors in most components and locations, with a greater effect observed in liver SBRTs. ConclusionsThe corrections made with IF-CBCT during SBRT treatments were not negligible. Both DIBH systems were effective in managing respiratory movements. However, the spirometry-based system was slightly more accurate. In addition, US monitoring of the prostate appeared to be useful in reducing target shift.

2.5D deep learning based on multi-parameter MRI to differentiate primary lung cancer pathological subtypes in patients with brain metastases

BackgroundBrain metastases (BMs) represents a severe neurological complication stemming from cancers originating from various sources. It is a highly challenging clinical task to accurately distinguish the pathological subtypes of brain metastatic tumors from lung cancer (LC).The utility of 2.5-dimensional (2.5D) deep learning (DL) in distinguishing pathological subtypes of LC with BMs is yet to be determined. MethodsA total of 250 patients were included in this retrospective study, divided in a 7:3 ratio into training set (N=175) and testing set (N=75). We devised a method to assemble a series of two-dimensional (2D) images by extracting adjacent slices from a central slice in both superior-inferior and anterior-posterior directions to form a 2.5D dataset. Multi-Instance learning (MIL) is a weakly supervised learning method that organizes training instances into “bags” and provides labels for entire bags, with the purpose of learning a classifier based on the labeled positive and negative bags to predict the corresponding class for an unknown bag. Therefore, we employed MIL to construct a comprehensive 2.5D feature set. Then we used the single-slice as input for constructing the 2D model. DL features were extracted from these slices using the pre-trained ResNet101. All feature sets were inputted into the support vector machine (SVM) for evaluation. The diagnostic performance of the classification models were evaluated using five-fold cross-validation, with accuracy and area under the curve (AUC) metrics calculated for analysis. ResultsThe optimal performance was obtained using the 2.5D DL model, which achieved the micro-AUC of 0.868 (95% confidence interval [CI], 0.817–0.919) and accuracy of 0.836 in the test cohort. The 2D model achieved the micro-AUC of 0.836 (95 % CI, 0.778–0.894) and accuracy of 0.827 in the test cohort. ConclusionsThe proposed 2.5D DL model is feasible and effective in identifying pathological subtypes of BMs from lung cancer.

Optimal Correction Strategy of Image Guided Radiation Therapy Including the Paraortic Lymph Node Region in Patients With Cervical Cancers

The clinically accepted planning target volume margin for radiation therapy to the paraortic nodal region in cervical cancer patients is 5 mm. However, the comprehensive alignment and variability from the pelvic bone to all lumbar vertebrae are undetermined. This study aims to quantify the residual setup errors between the pelvic bone and lumbar vertebrae and determine the optimal correction strategy for patients with cervical cancer. Fifteen patients underwent pretreatment mega-voltage computed tomography scans (375 total fractions). Residual setup errors and required margins for each lumbar vertebra were calculated based on registrations accounting for pelvic rotation and translation. The systematic residual errors (1 SD) at L1, L2, L3, L4, and L5 using pelvic bone registration were 6.5, 4.9, 3.1, 1.5, and 0.6 mm in the anterior-posterior (AP) direction, 3.1, 2.3, 1.4, 0.6, and 0.3 mm in the right-left direction, and 2.7, 2.2, 1.7, 1.0, and 0.5 mm in the superior-inferior direction, respectively. The residual setup errors were the largest in the AP direction. Registration based on the pelvic bone required margins in the AP direction of 16.0, 12.1, 7.7, 3.6, and 1.3 mm for L1, L2, L3, L4, and L5, respectively, whereas registration based on L3 required margins of 8.8, 4.8, 4.4, 7.1, and 7.7 mm for L1, L2, L4, L5, and pelvic bone, respectively. Considerable local setup variability was found in patients with cervical cancer. After reviewing the corrective strategies, we determined that L3-based registration effectively minimized the required margins.

Potential anatomical triggers for plan adaptation of cervical cancer external beam radiotherapy.

This study aimed to identify potential anatomical variation triggers using magnetic resonance imaging for plan adaption of cervical cancer patients to ensure dose requirements were met over an external beam radiotherapy course. Magnetic resonance images (MRIs) acquired before and during treatment were rigidly registered to a pre-treatment computerised tomography (CT) image for 11 retrospective cervix cancer datasets. Target volumes (TVs) and organs at risk (OARs) were delineated on both MRIs and propagated onto the CT. Treatment plans were generated based on the pre-treatment contours and applied to the mid-treatment contours. Anatomical and dosimetric changes between each timepoint were assessed. The anatomical changes included the change in centroid position and volume size. Dosimetric changes included the V30Gy and V40Gy for the OARs, and V95%, V100%, D95% and D98% for the TVs. Correlation with dosimetric and anatomical changes were assessed to determine potential replan triggers. Changes in the bowel volume and position in the superior-inferior direction, and the high-risk CTV anterior posterior position were highly correlated with a change in dose to the bowel and target, respectively. Hence changes in bowel and high-risk CTV could be used as a potential replan triggers.

Development and first implementation of a novel multi-modality cardiac motion and dosimetry phantom for radiotherapy applications.

Cardiac applications in radiation therapy are rapidly expanding including magnetic resonance guided radiation therapy (MRgRT) for real-time gating for targeting and avoidance near the heart or treating ventricular tachycardia (VT). This work describes the development and implementation of a novel multi-modality and magnetic resonance (MR)-compatible cardiac phantom. The patient-informed 3D model was derived from manual contouring of a contrast-enhanced Coronary Computed Tomography Angiography scan, exported as a Stereolithography model, then post-processed to simulate female heart with an average volume. The model was 3D-printed using Elastic50A to provide MR contrast to water background. Two rigid acrylic modules containing cardiac structures were designed and assembled, retrofitting to an MR-safe programmable motor to supply cardiac and respiratory motion in superior-inferior directions. One module contained a cavity for an ion chamber (IC), and the other was equipped with multiple interchangeable cavities for plastic scintillation detectors (PSDs). Images were acquired on a 0.35 T MR-linac for validation of phantom geometry, motion, and simulated online treatment planning and delivery. Three motion profiles were prescribed: patient-derived cardiac (sine waveform, 4.3mm peak-to-peak, 60 beats/min), respiratory (cos4 waveform, 30mm peak-to-peak, 12 breaths/min), and a superposition of cardiac (sine waveform, 4mm peak-to-peak, 70 beats/min) and respiratory (cos4 waveform, 24mm peak-to-peak, 12 breaths/min). The amplitude of the motion profiles was evaluated from sagittal cine images at eight frames/s with a resolution of 2.4mm × 2.4mm. Gated dosimetry experiments were performed using the two module configurations for calculating dose relative to stationary. A CT-based VT treatment plan was delivered twice under cone-beam CT guidance and cumulative stationary doses to multi-point PSDs were evaluated. No artifacts were observed on any images acquired during phantom operation. Phantom excursions measured 49.3±25.8%/66.9±14.0%, 97.0±2.2%/96.4±1.7%, and 90.4±4.8%/89.3±3.5% of prescription for cardiac, respiratory, and cardio-respiratory motion profiles for the 2-chamber (PSD) and 12-substructure (IC) phantom modules respectively. In the gated experiments, the cumulative dose was<2% from expected using the IC module. Real-time dose measured for the PSDs at 10Hz acquisition rate demonstrated the ability to detect the dosimetric consequences of cardiac, respiratory, and cardio-respiratory motion when sampling of different locations during a single delivery, and the stability of our phantom dosimetric results over repeated cycles for the high dose and high gradient regions. For the VT delivery, high dose PSD was<1% from expected (5-6 cGy deviation of 5.9Gy/fraction) and high gradient/low dose regions had deviations<3.6% (6.3 cGy less than expected 1.73Gy/fraction). A novel multi-modality modular heart phantom was designed, constructed, and used for gated radiotherapy experiments on a 0.35 T MR-linac. Our phantom was capable of mimicking cardiac, cardio-respiratory, and respiratory motion while performing dosimetric evaluations of gated procedures using IC and PSD configurations. Time-resolved PSDs with small sensitive volumes appear promising for low-amplitude/high-frequency motion and multi-point data acquisition for advanced dosimetric capabilities. Illustrating VT planning and delivery further expands our phantom to address the unmet needs of cardiac applications in radiotherapy.

Planar biaxial testing of CXL strengthening effects

The stiffening effect of corneal crosslinking (CXL) treatment, a therapeutic approach for managing the progression of keratoconus, has been primarily investigated using uniaxial tensile experiments. However, this testing technique has several drawbacks and is unable to measure the mechanical response of cornea under a multiaxial loading state. In this work, we used biaxial mechanical testing method to characterize biomechanical properties of porcine cornea before and after CXL treatment. We also investigated the influence of preconditioning on measured properties and used TEM images to determine microstructural characteristics of the extracellular matrix. The conventional method of CXL treatment was used for crosslinking the porcine cornea. The biaxial experiments were done by an ElectroForce TestBench system at a stretch ratio of 1:1 and a displacement rate of 2 mm/min with and without preconditioning. The experimental measurements showed no significant difference in the mechanical properties of porcine cornea along the nasal temporal (NT) and superior inferior (SI) direction. Furthermore, the CXL therapy significantly enhanced the mechanical properties along both directions without creating anisotropic response. The samples tested with preconditioning showed significantly stiffer response than those tested without preconditioning. The TEM images showed that the CXL therapy did not increase the diameter of collagen fibers but significantly decreased their interfibrillar spacing, consistent with the mechanical property improvement of CXL treated samples.

Fully automated determination of robotic pedicle screw accuracy and precision utilizing computer vision algorithms

Historically, pedicle screw accuracy measurements have relied on CT and expert visual assessment of the position of pedicle screws relative to preoperative plans. Proper pedicle screw placement is necessary to avoid complications, cost and morbidity of revision procedures. The aim of this study was to determine accuracy and precision of pedicle screw insertion via a novel computer vision algorithm using preoperative and postoperative computed tomography (CT) scans. Three cadaveric specimens were utilized. Screw placement planning on preoperative CT was performed according to standard clinical practice. Two experienced surgeons performed bilateral T2–L4 instrumentation using robotic-assisted navigation. Postoperative CT scans of the instrumented levels were obtained. Automated segmentation and computer vision techniques were employed to align each preoperative vertebra with its postoperative counterpart and then compare screw positions along all three axes. Registration accuracy was assessed by preoperatively embedding spherical markers (tantalum beads) to measure discrepancies in landmark alignment. Eighty-eight pedicle screws were placed in 3 cadavers’ spines. Automated registrations between pre- and postoperative CT achieved sub-voxel accuracy. For the screw tip and tail, the mean three-dimensional errors were 1.67 mm and 1.78 mm, respectively. Mean angular deviation of screw axes from plan was 1.58°. For screw mid-pedicular accuracy, mean absolute error in the medial–lateral and superior–inferior directions were 0.75 mm and 0.60 mm, respectively. This study introduces automated algorithms for determining accuracy and precision of planned pedicle screws. Our accuracy outcomes are comparable or superior to recent robotic-assisted in vivo and cadaver studies. This computerized workflow establishes a standardized protocol for assessing pedicle screw placement accuracy and precision and provides detailed 3D translational and angular accuracy and precision for baseline comparison.

Model-based Roentgen Stereophotogrammetric Analysis (RSA) of polyethylene implants

Model-based Roentgen Stereophotogrammetric Analysis (RSA) is able to measure the migration of metallic prostheses with submillimeter accuracy through contour-detection and 3D surface model matching techniques. However, contour-detection is only possible if the prosthesis is clearly visible in the radiograph; consequently Model-based RSA cannot be directly used for polymeric materials due to their limited X-ray attenuation; this is especially clinically relevant for all-polyethylene implants. In this study the radiopacity of unicompartmental Ultra-High Molecular Weight Polyethylene (UHMWPE) knee bearings was increased by diffusing an oil-based contrast agent into the surface to create three different levels of surface radiopacity. Model-based RSA was performed on the bearings alone, the bearings alongside a metallic component held in position using a phantom, the bearings cemented into a Sawbone tibia, and the bearings at different distances from the femoral component. For each condition the precision and accuracy of zero motion of Model-based RSA were assessed. The radiopaque bearings could be located in the stereo-radiographs using Model-based RSA an accuracy comparable to metallic parts for translational movements (0.03 mm to 0.50 mm). For rotational movements, the accuracy was lower (0.1∘ to 3.0∘). The measurement accuracy was compared for all the radiopacity levels and no significant difference was found (p=0.08). This study demonstrates that contrast enhanced radiopaque polyethylene can be used for Model-based RSA studies and has equivalent translational measurement precision to metallic parts in the superior-inferior direction.

Comparing immobilisation devices in gynaecological external beam radiotherapy: improving inter-fraction reproducibility of pelvic tilt.

The aim was to determine which immobilisation device improved inter-fraction reproducibly of pelvic tilt and required the least pre-treatment setup and planning interventions. Sixteen patients were retrospectively reviewed, eight immobilised using the BodyFIX system (BodyFIX®, Elekta, Stockholm, Sweden) and eight using the Butterfly Board (BB) (Bionix Radiation Therapy, Toledo, OH, USA). The daily pre-treatment images were reviewed to assess setup variations between each patient and groups for pelvic tilt, pubic symphysis, sacral promontory and the fifth lumbar spine (L5). Compared with the planning CT, pelvic tilt for most patients was within ±2° using the BodyFIX and ± 4° for the BB. The Butterfly Board had a slightly higher variance both for patient-to-patient (standard deviation of the systematic error) and day-to-day error (standard deviation of the random error). Variance in position between individual patients and the two stabilisation devices were minimal in the anterior-posterior (AP) and superior-inferior (SI) direction for the pubic symphysis, sacral promontory and L5 spine. Re-imaged fractions due to pelvic tilt reduced by about half when BodyFIX was used (39.1% BB, 19.4% BodyFIX). One patient treated with the BB required a re-scan for pelvic tilt. Three patients required a re-scan for body contour variations (two using BodyFIX and one with the BB). BodyFIX resulted in a more accurate inter-fraction setup and efficient treatment and is used as the standard stabilisation for gynaecological patients at our centre. It reduced the pelvic tilt variance and reduced the need for re-imaging pre-treatment by half.

Evaluating intra-fractional tumor motion in lung stereotactic radiotherapy with deep inspiration breath-hold.

To evaluate the intra-fractional tumor motion in lung stereotactic body radiotherapy (SBRT) with deep inspiration breath-hold (DIBH), and to investigate the adequacy of the current planning target volume (PTV) margins. Twenty-eight lung SBRT patients with DIBH were selected in this study. Among the lesions, twenty-three were at right or left lower lobe, two at right middle lobe, and three at right or left upper lobe. Post-treatment gated cone-beam computed tomography (CBCT) was acquired to quantify the intra-fractional tumor shift at each treatment. These obtained shifts were then used to calculate the required PTV margin, which was compared with the current applied margin of 5mm margin in anterior-posterior (AP) and right-left (RL) directions and 8mm in superior-inferior (SI) direction. The beam delivery time was prolonged with DIBH. The actual beam delivery time with DIBH (Tbeam_DIBH) was compared with the beam delivery time without DIBH (Tbeam_wo_DIBH) for the corresponding SBRT plan. A total of 113 treatments were analyzed. At six treatments (5.3%), the shifts exceeded the tolerance defined by the current PTV margin. The average shifts were 0.0±1.9mm, 0.1±1.5mm, and -0.5±3.7mm in AP, RL, and SI directions, respectively. The required PTV margins were determined to be 4.5, 3.9, and 7.4mm in AP, RL, and SI directions, respectively. The average Tbeam_wo_DIBH and Tbeam_DIBH were 2.4±0.4 min and 3.6±1.5 min, respectively. The average treatment slot for lung SBRT with DIBH was 25.3±7.9 min. Intra-fractional tumor motion is the predominant source of treatment uncertainties in CBCT-guided lung SBRT with DIBH. The required PTV margin should be determined based on data specific to each institute, considering different techniques and populations. Our data indicate that our current applied PTV margin is adequate, and it is possible to reduce further in the RL direction. The time increase of Tbeam_DIBH, relative to the treatment slot, is not clinically significant.

Navigator-based motion compensation for liver BOLD measurement with five-echo SAGE EPI and breath-hold task.

The purpose of this work is to apply multi-echo spin- and gradient-echo (SAGE) echo-planar imaging (EPI) combined with a navigator-based (NAV) prospective motion compensation method for a quantitative liver blood oxygen level dependent (BOLD) measurement with a breath-hold (BH) task. A five-echo SAGE sequence was developed to quantitatively measure T2 and T2* to depict function with sufficient signal-to-noise ratio, spatial resolution and sensitivity to BOLD changes induced by the BH task. To account for respiratory motion, a navigator was employed in the form of a single gradient-echo projection readout, located at the diaphragm along the inferior-superior direction. Prior to each transverse imaging slice of the spin-echo EPI-based readouts, navigator acquisition and fat suppression were incorporated. Motion data was obtained from the navigator and transmitted back to the sequence, allowing real-time adjustments to slice positioning. Six healthy volunteers and three patients with liver carcinoma were included in this study. Quantitative T2 and T2* were calculated at each time point of the BH task. Parameters of t value from first-level analysis using a general linear model and hepatovascular reactivity (HVR) of Echo1, T2 and T2* were calculated. The motion caused by respiratory activity was successfully compensated using the navigator signal. The average changes of T2 and T2* during breath-hold were about 1% and 0.7%, respectively. With the help of NAV prospective motion compensation whole liver t values could be obtained without motion artifacts. The quantified liver T2 (34.7 ± 0.7 ms) and T2* (29 ± 1.2 ms) values agreed with values from literature. In healthy volunteers, the distribution of statistical t value and HVR was homogeneous throughout the whole liver. In patients with liver carcinoma, the distribution of t value and HVR was inhomogeneous due to metastases or therapy. This study demonstrates the feasibility of using a NAV prospective motion compensation technique in conjunction with five-echo SAGE EPI for the quantitative measurement of liver BOLD with a BH task.

Deformable vector fields warping for modelling of irregular breathing.

Purpose&#xD;4D computed tomography (4DCT) is the clinical standard to image organ motion in radiotherapy, although it is limited in imaging breathing variability. We propose a method to transfer breathing motion across longitudinal imaging datasets to include intra-patient variability and verify its performance in lung cancer patients. &#xD;Methods &#xD;Five repeated control 4DCTs for 6 non-small cell lung cancer patients were combined into multi-breath datasets (m4DCT) by merging stages of deformable image registration to isolate respiratory motion. The displacement of the centre of mass of the primary tumour and its volume changes were evaluated to quantify intra-patient differences. Internal target volumes defined on the m4DCT were compared with those conventionally drawn on the 4DCT.&#xD;Results &#xD;Motion analysis suggests no discontinuity at the junction between successive breaths, confirming the method's ability to merge repeated imaging into a continuum. Motion (variability) is primarily in superior-inferior direction and goes from 14.4 mm (8.7 mm) down to 0.1 mm (0.6 mm), respectively for tumours located in the lower lobes or most apical ones. On average, up to 65% and 74% of the tumour volume was subject to expansion or contraction in the inhalation and exhalation phases. These variations lead to an enlargement of the ITV up to 8% of its volume in our dataset.&#xD;Conclusion &#xD;4DCT can be extended to model variable breathing motion by adding synthetic phases from multiple time-resolved images. The inclusion of this improved knowledge of patients' breathing allows better definition of treatment volumes and their margins for radiation therapy.&#xD.