Four-dimensional Computer Tomography Research Articles

Role of four-dimensional computer tomography (4D-CT) in non-localising and discordant first-line imaging in primary hyperparathyroidism.

Accurate preoperative localisation of parathyroid adenoma is imperative for the success of minimally invasive parathyroidectomy (MIP). Our study aimed to evaluate the role of four-dimensional computer tomography (4D-CT) scan as an imaging modality in patients with failed and discordant localisation reported in the first-line imaging modalities (ultrasonography and 99mTc-MIBI-SPECT/CT). This is a prospective cohort study performed at a university teaching centre from March 2013 to July 2021. All patients with primary hyperparathyroidism who had failed localisation by ultrasonography and 99mTc-MIBI-SPECT/CT (SpCT), or discordance between them, had 4D-CT performed in this study. One hundred and two sporadic cases of pHPT with failed/discordant first-line imaging had 4D-CT imaging prior to parathyroidectomy. In 102 patients, 105 parathyroid adenomas were reported on histopathology. 4D-CT was able to localise 78% of them to the correct side and 64% to the correct quadrant in 102 patients, as compared with US (correct side 21%, correct quadrant 16%) and 99mTc-MIBI-SPECT/CT (correct side 36%, correct quadrant 31%). 4D-CT had a sensitivity, precision, accuracy and F1 score for correct quadrant localisation as 79%, 81%, 66% and 80%; and for correct side localisation as 82%, 98%, 80% and 89%, respectively. 4D-CT was able to identify three ectopic adenomas (two in superior mediastinum and one in the oesophageal wall) which were not detected on US or SpCT. 4D-CT was found to be sensitive and accurate in preoperative localising of the diseased parathyroid glands after failed/discordant US and SpCT. This led to more patients being offered MIP as the primary surgery and improved operative outcomes.

Persistent and Recurrent Primary Hyperparathyroidism: Etiological Factors and Pre-Operative Evaluation.

Primary hyperparathyroidism (pHPT) is the most common cause of hypercalcemia and currently the only definitive treatment is surgery. Although the success rate of parathyroidectomy is over 95% in experienced centers, surgical failure is the most common complication today. Persistent HPT (perHPT) is defined as persistence of hypercalcemia after parathyroidectomy or recurrence of hypercalcemia within the first 6 months, and recurrence of hypercalcemia after a normocalcemic period of more than 6 months is defined as recurrent HPT (recHPT). In the literature, perHPT is reported to be 2-22%, and the rate of recHPT is 1-15%. perHPT is often associated with misdiagnosed pathology or inadequate resection of hyperfunctioning parathyroid tissue, recHPT is associated with newly developing pathology from potentially pathologically natural tissue left in situ at the initial surgery. In the pre-operative evaluation, the initial diagnosis of pHPT and the diagnosis of perHPT or rec HPT should be confirmed in patients who are evaluated with a pre-diagnosis (suspect) of perHPT and recHPT. Surgery is recommended if it meets any of the recommendations in surgical guidelines, as in patients with pHPT, and there are no surgical contraindications. The first preoperative localization studies, surgical notes, operation drawings, if any, intraoperative PTH results, pathological results, and post-operative biochemical results of these patients should be examined. Localization studies with preoperative imaging methods should be performed in all patients with perHPT and recHPT with a confirmed diagnosis and surgical indication. The first-stage imaging methods are ultrasonography and Tc99m sestamibi single photon tomography Tc99mMIBI SPECT or hybrid imaging method, which is combined with both single-photon emission computed tomography and computed tomography (SPECT/CT). The combination of USG and sestamibi scintigraphy increases the localization of the pathological gland. In the secondary stage, Four-Dimensional computer tomography (4D-CT) or dynamic 4-dimensional Magnetic Resonance Imaging (4D-MRI) can be applied. It is focused on as a secondary stage imaging method, especially when the lesion cannot be detected by conventional methods. Positron Emission Tomography (PET) and PET/CT examinations with 11C-choline or 18F-fluorocholine are promising imaging modalities. Invasive examinations can rarely be performed in patients in whom suspicious, incompatible or pathological lesion cannot be detected in noninvasive imaging methods. Bilateral jugular vein sampling, selective venous sampling, parathyroid arteriography, imaging-guided fine-needle aspiration biopsy, and parathormone washout are invasive methods.

On the evaluation of mobile target trajectory between four-dimensional computer tomography and four-dimensional cone-beam computer tomography.

PurposeFor mobile lung tumors, four‐dimensional computer tomography (4D CT) is often used for simulation and treatment planning. Localization accuracy remains a challenge in lung stereotactic body radiation therapy (SBRT) treatments. An attractive image guidance method to increase localization accuracy is 4D cone‐beam CT (CBCT) as it allows for visualization of tumor motion with reduced motion artifacts. However, acquisition and reconstruction of 4D CBCT differ from that of 4D CT. This study evaluates the discrepancies between the reconstructed motion of 4D CBCT and 4D CT imaging over a wide range of sine target motion parameters and patient waveforms.MethodsA thorax motion phantom was used to examine 24 sine motions with varying amplitudes and cycle times and seven patient waveforms. Each programmed motion was imaged using 4D CT and 4D CBCT. The images were processed to auto segment the target. For sine motion, the target centroid at each phase was fitted to a sinusoidal curve to evaluate equivalence in amplitude between the two imaging modalities. The patient waveform motion was evaluated based on the average 4D data sets.ResultsThe mean difference and root‐mean‐square‐error between the two modalities for sine motion were −0.35 ± 0.22 and 0.60 mm, respectively, with 4D CBCT slightly overestimating amplitude compared with 4D CT. The two imaging methods were determined to be significantly equivalent within ±1 mm based on two one‐sided t tests (p < 0.001). For patient‐specific motion, the mean difference was 1.5 ± 2.1 (0.8 ± 0.6 without outlier), 0.4 ± 0.3, and 0.8 ± 0.6 mm for superior/inferior (SI), anterior/posterior (AP), and left/right (LR), respectively.ConclusionIn cases where 4D CT is used to image mobile tumors, 4D CBCT is an attractive localization method due to its assessment of motion with respect to 4D CT, particularly for lung SBRT treatments where accuracy is paramount.

Development of a markerless tumor-tracking algorithm using prior four-dimensional cone-beam computed tomography.

Respiratory motion management is a huge challenge in radiation therapy. Respiratory motion induces temporal anatomic changes that distort the tumor volume and its position. In this study, a markerless tumor-tracking algorithm was investigated by performing phase recognition during stereotactic body radiation therapy (SBRT) using four-dimensional cone-beam computer tomography (4D-CBCT) obtained at patient registration, and in-treatment cone-beam projection images. The data for 20 treatment sessions (five lung cancer patients) were selected for this study. Three of the patients were treated with conventional flattening filter (FF) beams, and the other two were treated with flattening filter-free (FFF) beams. Prior to treatment, 4D-CBCT was acquired to create the template projection images for 10 phases. In-treatment images were obtained at near real time during treatment. Template-based phase recognition was performed for 4D-CBCT re-projected templates using prior 4D-CBCT based phase recognition algorithm and was compared with the results generated by the Amsterdam Shroud (AS) technique. Visual verification technique was used for the verification of the phase recognition and AS technique at certain tumor-visible angles. Offline template matching analysis using the cross-correlation indicated that phase recognition performed using the prior 4D-CBCT and visual verification matched up to 97.5% in the case of FFF, and 95% in the case of FF, whereas the AS technique matched 83.5% with visual verification for FFF and 93% for FF. Markerless tumor tracking based on phase recognition using prior 4D-CBCT has been developed successfully. This is the first study that reports on the use of prior 4D-CBCT based on normalized cross-correlation technique for phase recognition.

Proton Beam Therapy for Unresectable Cholangiocarcinoma

To evaluate the treatment outcome and patterns of failure in patients with unresectable cholangiocarcinoma undergoing proton beam therapy (PBT). We retrospectively analyzed 22 patients with pathologically confirmed cholangiocarcinoma who were treated with definitive PBT from November 2015 to August 2017. Four-dimensional computer tomography (4D-CT) with and without intravenous contrast-enhancement was acquired with 2.5 mm slide thickness. A clinical target volume expansion of 5-10 mm was used. The internal target volume was generated based on the 4D-CT images, and respiratory gaiting was adopted in patients with tumor motion >10 mm. Treatment-related toxicities were recorded according to Common Terminology Criteria for Adverse Event version 4.0 (CTCAE v4.0). The study included 11 male and 11 female participants, with a median age of 68 years (range, 46-88 years). Intrahepatic, perihilar and distal extrahepatic, and gallbladder tumors were recorded in 12 (54%), 7 (32%), 1 (5%) and 2 (9%), respectively. The median tumor dimension was 7.0 cm (range, 3.8-18.2 cm). Stage IV, III and II was documented in 15 (68%), 5 (23%) and 2 (9%) patients, respectively. Tumor vascular invasion was observed in 5 (23%) patients, and 19 (86%) patients demonstrated biliary tract obstruction. The median PBT dose was 72.6 cobalt gray equivalent (CGE) (range, 39.6-72.6 CGE). Gemcitabine-based concomitant chemotherapy was administered in 15 (68%) patients. After a median follow-up of 14.3 months, the 1-year overall survival rate was 75%. Fifteen (68%) patients developed disease progression. Among them, one (5%) patients experienced in-field local failure, whereas 4 (18%) patients developed intrahepatic out-field recurrence. Distant metastasis (N = 10, 45%) was the predominant form of treatment failure. The 1-year local control and progression-free survival rates were 100% and 42%, respectively. Among the 19 patients who presented obstructive jaundice, normalization of total bilirubin level was recorded in 14 (74%) patients after PBT with or without biliary drainage. Grade 3 dermatitis and grade 4 duodenal ulcer occurred in 2 (9%) and 2 (9%) patients, respectively. PBT could lead to an excellent local control probability, sustainable relief of biliary tract obstruction and a favorable survival outcome in patients with unresectable cholangiocarcinoma. However, distant recurrence remains the primary reason of failure after PBT.

Prediction of Lung Motion From Four-Dimensional Computer Tomography (4DCT) Images Using Bayesian Registration and Trajectory Modelling

Respiratory motion causes difficulty in locating tumours in the thorax and upper abdomen for image-guided radiotherapy. Precisely predicting the respiratory-induced organ motion is still a challenging problem at present. In this paper, to predict the motion of lungs in a respiratory cycle, we propose a novel method comprising Bayesian registration and trajectory modelling based on cine four-dimensional computer tomography (4DCT) images. Specifically, we take the CT image captured at the end-inhale phase as the source image and those captured at other phases as the moving images. We then align the source image to each moving-phase image to generate the displacement fields using the Bayesian registration method. The lung-motion trajectory is then modelled based on a continuous time-related displacement field by linking the displacement fields at discrete phases. The results indicate that any point in the lungs at any given time is accurately predicted using the proposed method, which provides an alternative method of estimating the lung and tumour motions for radiation therapy.

Treatment of esophageal cancer with radiation therapy -a pan-Chinese survey of radiation oncologists.

Lots of controversies were found about the treatment in relation to radiation therapy (RT) for esophageal squamous cell carcinoma (ESCC). We designed a questionnaire of these controversies to do a pan-Chinese survey of radiation oncologists (ROs). For operable ESCC, 53% ROs chose surgery plus postoperative chemoradiotherapy (CRT), while 40% chose preoperative CRT plus surgery. For target volume of postoperative RT, most ROs (92%) would delineate tumor bed plus involved lymph nodes region before surgery. For definitive RT, most ROs (81%) would give patients higher RT dose to 60–65Gy. For radiation target volume, most ROs would give patients prophylactic irradiation of the bilateral superclavicular-lymph nodes region for cervical ESCC (93%), and the left gastric lymph nodes region for lower thoracic ESCC (72%). For the treatment of mediastinal lymph nodes, 72% ROs preferred elective nodal irradiation, while 28% did the involved nodal irradiation. For concurrent chemotherapy regimen, PF (5-Fu + cisplatin) and TP (cisplatin + paclitaxel) were used widely (49% and 46%, respectively). During simulation, four-dimensional computer tomography (4D CT) was not widely used (48%), even for cervical or lower thoracic ESCC (52%). For daily RT delivery, only 66% ROs would perform imaging guidance RT daily. In summary, more controversies existed in the treatment of ESCC with RT in China, including treatment strategy, radiation dose and target contour. Future goals include standardization of treatment strategy, radiation dose, and target contour, and application of 4D CT and daily imaging guidance, and pursuit of randomized trials in Chinese population.

Contour propagation using non-uniform cubic B-splines for lung tumor delineation in 4D-CT.

Accurate target delineation is a critical step in radiotherapy. In this study, a robust contour propagation method is proposed to help physicians delineate lung tumors in four-dimensional computer tomography (4D-CT) images efficiently and accurately. The proposed method starts with manually delineated contours on the reference phase. Each contour is fitted by a non-uniform cubic B-spline curve, and its deformation on the target phase is achieved by moving its control vertexes such that the intensity similarity between the two contours is maximized. Since contour is usually the boundary of lesion or tissue which may deform quite differently from the tissues outside the boundary, the proposed method treats each contour as a deformable entity, a non-uniform cubic B-spline curve, and focuses on the registration of contour entity instead of the entire image to avoid the deformation of contour to be smoothed by its surrounding tissues, meanwhile to greatly reduce the time consumption while keeping the accuracy of the contour propagation. Eighteen 4D-CT cases with 444 gross tumor volume (GTV) contours manually delineated slice by slice on the maximal inhale and exhale phases are used to verify the proposed method. The Jaccard similarity coefficient (JSC) between the propagated GTV and the manually delineated GTV is 0.885±0.026, and the Hausdorff distance (HD) is [Formula: see text] mm. In addition, the time for propagating GTV to all the phases is 3.67±3.41 minutes. The results are better than fast adaptive stochastic gradient descent (FASGD) B-spline method, 3D+t B-spline method and diffeomorphic Demons method. The proposed method is useful to help physicians delineate target volumes efficiently and accurately.

Resolution enhancement of lung 4D‐CT data using multiscale interphase iterative nonlocal means

Four-dimensional computer tomography (4D-CT) has been widely used in lung cancer radiotherapy due to its capability in providing important tumor motion information. However, the prolonged scanning duration required by 4D-CT causes considerable increase in radiation dose. To minimize the radiation-related health risk, radiation dose is often reduced at the expense of interslice spatial resolution. However, inadequate resolution in 4D-CT causes artifacts and increases uncertainty in tumor localization, which eventually results in extra damages of healthy tissues during radiotherapy. In this paper, the authors propose a novel postprocessing algorithm to enhance the resolution of lung 4D-CT data. The authors' premise is that anatomical information missing in one phase can be recovered from the complementary information embedded in other phases. The authors employ a patch-based mechanism to propagate information across phases for the reconstruction of intermediate slices in the longitudinal direction, where resolution is normally the lowest. Specifically, the structurally matching and spatially nearby patches are combined for reconstruction of each patch. For greater sensitivity to anatomical details, the authors employ a quad-tree technique to adaptively partition the image for more fine-grained refinement. The authors further devise an iterative strategy for significant enhancement of anatomical details. The authors evaluated their algorithm using a publicly available lung data that consist of 10 4D-CT cases. The authors' algorithm gives very promising results with significantly enhanced image structures and much less artifacts. Quantitative analysis shows that the authors' algorithm increases peak signal-to-noise ratio by 3-4 dB and the structural similarity index by 3%-5% when compared with the standard interpolation-based algorithms. The authors have developed a new algorithm to improve the resolution of 4D-CT. It outperforms the conventional interpolation-based approaches by producing images with the markedly improved structural clarity and greatly reduced artifacts.

Volume Modulated Arc Therapy (VMAT) for pulmonary Stereotactic Body Radiotherapy (SBRT) in patients with lesions in close approximation to the chest wall

Purpose: Chest wall pain and discomfort has been recognized as a significant late effect of radiation therapy in historical and modern treatment models. Stereotactic Body Radiotherapy (SBRT) is becoming an important treatment tool in oncology care for patients with intrathoracic lesions. For lesions in close approximation to the chest wall with motion management, SBRT techniques can deliver high dose to the chest wall. As an unintended target of consequence, there is possibility of imposing significant chest wall pain and discomfort as a late effect of therapy. The purpose of this paper is to evaluate the potential role of Volume Modulated Arc Therapy (VMAT) technologies in decreasing chest wall dose in SBRT treatment of pulmonary lesions in close approximation to the chest wall.Materials and Methods: Ten patients with pulmonary lesions of various sizes and tomography in close approximation to the chest wall were selected for retrospective review. All volumes including tumor target, chest wall, ribs, and lung were contoured with maximal intensity projection maps and four-dimensional computer tomography planning. Radiation therapy planning consisted of static techniques including Intensity Modulated Radiation Therapy compared to VMAT therapy to a dose of 60 Gy in 12 Gy fraction dose. Dose volume histogram to rib, chest wall, and lung were compared between plans with statistical analysis.Results: In all patients, dose and volume were improved to ribs and chest wall using VMAT technologies compared to static field techniques. On average, volume receiving 30 Gy to the chest wall was improved by 74%; the ribs by 60%. In only one patient did the VMAT treatment technique increase pulmonary volume receiving 20 Gy (V20).Conclusions: VMAT technology has potential of limiting radiation dose to sensitive chest wall regions in patients with lesions in close approximation to this structure. This would also have potential value to lesions treated with SBRT in other body regions where targets abut critical structures.

Patient-specific respiratory models using dynamic 3D MRI: Preliminary volunteer results

Organ and tumour motion has a significant impact on the planning and delivery of radiotherapy treatment. At present imaging modality such as four-dimensional computer tomography (4DCT) cannot be used to measure the variability of motion between different respiratory cycles. To create reliable motion models, one needs to acquire volumetric data sets of the lungs with sufficient sampling of the breathing cycle. In this paper we investigate the use of highly parallel MRI to acquire such data. A 32 channel coil in conjunction with a balanced SSFP sequence and a SENSE factor of 6 were used to acquire volumetric data sets in five healthy volunteers. The acquisition was repeated for seven series of different breathing patterns. The data acquired was of sufficient spatial resolution (5 × 5 × 5 mm3) and image quality to carry out automated non-rigid registration. The acquisition rate (c.a. 2 volumes per second) allowed for a meaningful sampling of the different respiratory curves that were automatically obtained from the skin surface motion. This acquisition technique should provide images of high enough quality to create statistical respiratory models.

4D CT image acquisition errors in SBRT of liver identified using correlation

In the AAPM Report 80,( 1 ) the imaging modality of 4D CT and respiration‐correlated CT was declared a “promising solution for obtaining high‐quality CT data in the presence of respiratory motion”. To gather anatomically correct data over time, the existence of correlation between the internal organ movement and an external surrogate has to be assumed. For the in‐house evaluation of such correlation, we retrospectively analyzed 21 four‐dimensional computer tomography (4D CT) scans of five patients, out of which the artifacts experienced in three patients are shown here. To provide context and a baseline for the analysis of patient motion, a real‐tissue liver phantom was used with a solid water block and liver tissue. The superior–inferior motion of fiducials in phantom and patients was correlated to the recorded anterior–posterior motion of an external surrogate marker on the chest. The use of a solid water block yielded a measurable correlation coefficient of 0.98 or better using a sinusoidal animation pattern. With sinusoidally‐animated liver tissue, the minimum correlation observed was 0.96. Comparing this to retrospective patient data, we found three cases of a change in the correlation coefficient, or simply a low correlation. The source of this low correlation was investigated by careful examination of the breathing traces and the CT‐phase assignments used to reconstruct the datasets. Consequences of nonregular breathing are elaborated on. We demonstrate the impact of wrong phase assignments and missing image information in the 4D CT phase sampling processes. We also show how daily patient‐based correlation analysis can indicate changes in breathing traces, which can be significant enough to decrease, or completely eliminate, previously existing correlation.PACS numbers: 87.57.‐s, 87.57.Q‐, 87.57.cp, 87.57.N‐, 87.55.Qr

Influence of increased target dose inhomogeneity on margins for breathing motion compensation in conformal stereotactic body radiotherapy

BackgroundBreathing motion should be considered for stereotactic body radiotherapy (SBRT) of lung tumors. Four-dimensional computer tomography (4D-CT) offers detailed information of tumor motion. The aim of this work is to evaluate the influence of inhomogeneous dose distributions in the presence of breathing induced target motion and to calculate margins for motion compensation.MethodsBased on 4D-CT examinations, the probability density function of pulmonary tumors was generated for ten patients. The time-accumulated dose to the tumor was calculated using one-dimensional (1D) convolution simulations of a 'static' dose distribution and target probability density function (PDF). In analogy to stereotactic body radiotherapy (SBRT), different degrees of dose inhomogeneity were allowed in the target volume: minimum doses of 100% were prescribed to the edge of the target and maximum doses varied between 102% (P102) and 150% (P150). The dose loss due to breathing motion was quantified and margins were added until this loss was completely compensated.ResultsWith the time-weighted mean tumor position as the isocentre, a close correlation with a quadratic relationship between the standard deviation of the PDF and the margin size was observed. Increased dose inhomogeneity in the target volume required smaller margins for motion compensation: margins of 2.5 mm, 2.4 mm and 1.3 mm were sufficient for compensation of 11.5 mm motion range and standard deviation of 3.9 mm in P105, P125 and P150, respectively. This effect of smaller margins for increased dose inhomogeneity was observed for all patients. Optimal sparing of the organ-at-risk surrounding the target was achieved for dose prescriptions P105 to P118. The internal target volume concept over-compensated breathing motion with higher than planned doses to the target and increased doses to the surrounding normal tissue.ConclusionTreatment planning with inhomogeneous dose distributions in the target volume required smaller margins for compensation of breathing induced target motion with the consequence of lower doses to the surrounding organs-at-risk.

An optical flow based method for improved reconstruction of 4D CT data sets acquired during free breathing

Respiratory motion degrades anatomic position reproducibility and leads to issues affecting image acquisition, treatment planning, and radiation delivery. Four-dimensional (4D) computer tomography (CT) image acquisition can be used to measure the impact of organ motion and to explicitly account for respiratory motion during treatment planning and radiation delivery. Modern CT scanners can only scan a limited region of the body simultaneously and patients have to be scanned in segments consisting of multiple slices. A respiratory signal (spirometer signal or surface tracking) is used to reconstruct a 4D data set by sorting the CT scans according to the couch position and signal coherence with predefined respiratory phases. But artifacts can occur if there are no acquired data segments for exactly the same respiratory state for all couch positions. These artifacts are caused by device-dependent limitations of gantry rotation, image reconstruction times and by the variability of the patient's respiratory pattern. In this paper an optical flow based method for improved reconstruction of 4D CT data sets from multislice CT scans is presented. The optical flow between scans at neighboring respiratory states is estimated by a non-linear registration method. The calculated velocity field is then used to reconstruct a 4D CT data set by interpolating data at exactly the predefined respiratory phase. Our reconstruction method is compared with the usually used reconstruction based on amplitude sorting. The procedures described were applied to reconstruct 4D CT data sets for four cancer patients and a qualitative and quantitative evaluation of the optical flow based reconstruction method was performed. Evaluation results show a relevant reduction of reconstruction artifacts by our technique. The reconstructed 4D data sets were used to quantify organ displacements and to visualize the abdominothoracic organ motion.