Visualization of 4D multimodal imaging data and its applications in radiotherapy planning.

PURPOSE: To explore the benefit of using 4D multimodal visualization and interaction techniques for defined radiotherapy planning tasks over a treatment planning system used in clinical routine (C-TPS) without dedicated 4D visualization. METHODS: We developed a 4D visualization system (4D-VS) with dedicated rendering and fusion of 4D multimodal imaging data based on a list of requirements developed in collaboration with radiation oncologists. We conducted a user evaluation in which the benefits of our approach were evaluated in comparison to C-TPS for three specific tasks: assessment of internal target volume (ITV) delineation, classification of tumor location in peripheral or central, and assessment of dose distribution. For all three tasks, we presented test cases for which we measured correctness, certainty, consistency followed by an additional survey regarding specific visualization features. RESULTS: Lower quality of the test ITVs (ground truth quality was available) was more likely to be detected using 4D-VS. ITV ratings were more consistent in 4D-VS and the classification of tumor location had a higher accuracy. Overall evaluation of the survey indicates 4D-VS provides better spatial comprehensibility and simplifies the tasks which were performed during testing. CONCLUSIONS: The use of 4D-VS has improved the assessment of ITV delineations and classification of tumor location. The visualization features of 4D-VS have been identified as helpful for the assessment of dose distribution during user testing.

Comparison of protocols with respiratory-gated (4D) motion compensation in PET/CT: open-source package for quantification of phantom image quality.

BACKGROUND: Patient's breathing affects the quality of chest images acquired with positron emission tomography/computed tomography (PET/CT) studies. Movement correction is required to optimize PET quantification in clinical settings. We present a reproducible methodology to compare the impact of different movement compensation protocols on PET image quality. Static phantom images were set as reference values, and recovery coefficients (RCs) were calculated from motion compensated images for the phantoms in respiratory movement. Image quality was evaluated in terms of: (1) volume accuracy (VA) with the NEMA phantom; (2) concentration accuracy (CA) by six refillable inserts within the electron density CIRS phantom; and (3) spatial resolution (R) with the Jaszczak phantom. Three different respiratory patterns were applied to the phantoms. We developed an open-source package to automatically analyze VA, CA and R. We compared 10 different movement compensation protocols available in the Philips Gemini TF-64 PET/CT (4-, 6-, 8- and 10-time bins, 20%-, 30%-, 40%-window width in Inhale and Exhale). RESULTS: The homemade package provided RC values for VA, CA and R of 102 PET images in less than 5 min. Results of the comparison of the 10 different protocols demonstrated the feasibility of the proposed method for quantifying the variations observed qualitatively. Overall, prospective protocols showed better motion compensation than retrospective. The best performance was obtained for the protocol Exhale 30% (0.3 s after maximum Exhale position and window width of 30%) with RC[Formula: see text], RC[Formula: see text] and RC[Formula: see text]. Among retrospective protocols, 8 Phase protocol showed the best performance. CONCLUSION: We provided an open-source package able to automatically evaluate the impact of motion compensation methods on PET image quality. A setup based on commonly available experimental phantoms is recommended. Its application for the comparison of 10 time-based approaches showed that Exhale 30% protocol had the best performance. The proposed framework is not specific to the phantoms and protocols presented on this study.

Respiratory 4D-Gating F-18 FDG PET/CT Scan for Liver Malignancies: Feasibility in Liver Cancer Patient and Tumor Quantitative Analysis.

PURPOSE: To evaluate the potential clinical role and effectiveness of respiratory 4D-gating F-18 FDG PET/CT scan for liver malignancies, relative to routine (3D) F-18 FDG PET/CT scan. MATERIALS AND METHODS: This study presented a prospective clinical study of 16 patients who received F-18 FDG PET/CT scan for known or suspected malignant liver lesions. Ethics approvals were obtained from the ethics committees of the Hong Kong Baptist Hospital and The Hong Kong Polytechnic University. Liver lesions were compared between the gated and ungated image sets, in terms of 1) volume measurement of PET image, 2) accuracy of maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and 3) accuracy of total lesion glycoses (TLG). Statistical analysis was performed by using a two-tailed paired Student t-test and Pearson correlation test. RESULTS: The study population consisted of 16 patients (9 males and 7 females; mean age of 65) with a total number of 89 lesions. The SUVmax and SUVmean measurement of the gated PET images was more accurate than that of the ungated PET images, compared to the static reference images. An average of 21.48% (p < 0.001) reduction of the tumor volume was also observed. The SUVmax and SUVmean of the gated PET images were improved by 19.81% (p < 0.001) and 25.53% (p < 0.001), compared to the ungated PET images. CONCLUSIONS: We have demonstrated the feasibility of implementing 4D PET/CT scan for liver malignancies in a prospective clinical study. The 4D PET/CT scan for liver malignancies could improve the quality of PET image by improving the SUV accuracy of the lesions and reducing image blurring. The improved accuracy in the classification and identification of liver tumors with 4D PET image would potentially lead to its increased utilization in target delineation of GTV, ITV, and PTV for liver radiotherapy treatment planning in the future.

FDG-PET Radiomics for Response Monitoring in Non-Small-Cell Lung Cancer Treated with Radiation Therapy.

The aim of this study is to identify clinically relevant image feature (IF) changes during chemoradiation and evaluate their efficacy in predicting treatment response. Patients with non-small-cell lung cancer (NSCLC) were enrolled in two prospective trials (STRIPE, PET-Plan). We evaluated 48 patients who underwent static (3D) and retrospectively-respiratory-gated 4D PET/CT scans before treatment and a 3D scan during or after treatment. Our proposed method rejects IF changes due to intrinsic variability. The IF variability observed across 4D PET is employed as a patient individualized normalization factor to emphasize statistically relevant IF changes during treatment. Predictions of overall survival (OS), local recurrence (LR) and distant metastasis (DM) were evaluated. From 135 IFs, only 17 satisfied the required criteria of being normally distributed across 4D PET and robust between 3D and 4D images. Changes during treatment in the area-under-the-curve of the cumulative standard-uptake-value histogram (δAUCCSH) within primary tumor discriminated (AUC = 0.87, Specificity = 0.78) patients with and without LR. The resulted prognostic model was validated with a different segmentation method (AUC = 0.83) and in a different patient cohort (AUC = 0.63). The quantification of tumor FDG heterogeneity by δAUCCSH during chemoradiation correlated with the incidence of local recurrence and might be recommended for monitoring treatment response in patients with NSCLC.

4D-CT Attenuation Correction in Respiratory-Gated PET for Hypoxia Imaging: Is It Really Beneficial?

Previous literature has shown that 4D respiratory-gated positron emission tomography (PET) is beneficial for quantitative analysis and defining targets for boosting therapy. However the case for addition of a phase-matched 4D-computed tomography (CT) for attenuation correction (AC) is less clear. We seek to validate the use of 4D-CT for AC and investigate the impact of motion correction for low signal-to-background PET imaging of hypoxia using radiotracers such as FAZA and FMISO. A new insert for the Modus Medicals' QUASAR™ Programmable Respiratory Motion Phantom was developed in which a 3D-printed sphere was placed within the "lung" compartment while an additional compartment is added to simulate muscle/blood compartment required for hypoxia quantification. Experiments are performed at 4:1 or 2:1 signal-to-background ratio consistent with clinical FAZA and FMISO imaging. Motion blur was significant in terms of SUVmax, mean, and peak for motion ≥1 cm and could be significantly reduced (from 20% to 8% at 2-cm motion) for all 4D-PET-gated reconstructions. The effect of attenuation method on precision was significant (σ2 hCT-AC = 5.5%/4.7%/2.7% vs σ2 4D-CT-AC = 0.5%/0.6%/0.7% [max%/peak%/mean% variance]). The simulated hypoxic fraction also significantly decreased under conditions of 2-cm amplitude motion from 55% to 20% and was almost fully recovered (HF = 0.52 for phase-matched 4D-CT) using gated PET. 4D-gated PET is valuable under conditions of low radiotracer uptake found in hypoxia imaging. This work demonstrates the importance of using 4D-CT for AC when performing gated PET based on its significantly improved precision over helical CT.

Respiratory Gating and the Performance of PET/CT in Pulmonary Lesions.

BACKGROUND: Motion artifacts related to the patient's breathing can be the cause of underestimation of the lesion uptake and can lead to missing of small lung lesions. The respiratory gating (RG) technology has demonstrated a significant increase in image quality. OBJECTIVE: The aim of this paper was to evaluate the advantages of RG technique on PET/CT performance in lung lesions. The impact of 4D-PET/CT on diagnosis (metabolic characterization), staging and re-staging lung cancer was also assessed, including its application for radiotherapy planning. Finally, new technologies for respiratory motion management were also discussed. METHODS: A comprehensive electronic search of the literature was performed by using Medline database (PubMed) searching "PET/CT", "gated" and "lung". Original articles, review articles, and editorials published in the last 10 years were selected, included and critically reviewed in order to select relevant articles. RESULTS: Many papers compared Standardized Uptake Value (SUV) in gated and ungated PET studies showing an increase in SUV of gated images, particularly for the small lesions located in medium and lower lung. In addition, other features as Metabolic Tumor Volume (MTV), Total Lesion Glycolysis (TLG) and textural-features presented differences when obtained from gated and ungated PET acquisitions. Besides the increase in quantification, gating techniques can determine an increase in the diagnostic accuracy of PET/CT. Gated PET/CT was evaluated for lung cancer staging, therapy response assessment and for radiation therapy planning. CONCLUSION: New technologies able to track the motion of organs lesion directly from raw PET data, can reduce or definitively solve problems (i.e.: extended acquisition time, radiation exposure) currently limiting the use of gated PET/CT in clinical routine.

Quantitative 4D-PET reconstruction for small animal using SMEIR-reconstructed 4D-CBCT.

Respiratory motions in small animals PET cause image degradation during reconstruction. This work aims to develop a motion compensated 4D-PET reconstruction method using accurate motion corrections and attenuation corrections from 4D-CBCT images reconstructed using a simultaneous motion estimation and image reconstruction (SMEIR) method. Projections of 4D-CBCT were calculated using a ray-tracing method on a digital 4D rat phantom, and list-mode data of 4D-PET with matched respiratory phases were simulated using the GATE Monte Carlo package. The respiratory rate was set at 1.0 second per cycle with 10 phases of 30 projection images each. 4D-CBCT images were reconstructed using the SMEIR method and motion information and linear attenuation from 4D-CBCT were subsequently used for motion compensated 4D-PET reconstruction and attenuation corrections. We quantitatively evaluate the reconstructed 4D-PET using the errors of tumor volume and standard uptake values of tumors with different sizes. The tumor motion was successfully reconstructed and showed good agreement with the original phantom. The proposed method reduced tumor volume errors and standard uptake value errors. For tumor diameters of 3.0, 4.5, and 6.0 mm, the tumor volume errors are 32.5%, 29.2% and 19.4% respectively with motion compensation and 45.1%, 37.5% and 20.2% respectively without compensation.

Accelerated PET kinetic maps estimation by analytic fitting method.

In this work, we propose and test a new approach for non-linear kinetic parameters' estimation from dynamic PET data. A technique is discussed, to derive an analytical closed-form expression of the compartmental model used for kinetic parameters' evaluation, using an auxiliary parameter set, with the aim of reducing the computational burden and speeding up the fitting of these complex mathematical expressions to noisy TACs. Two alternative algorithms based on numeric calculations are considered and compared to the new proposal. We perform a simulation study aimed at (i) assessing agreement between the proposed method and other conventional ways of implementing compartmental model fitting, and (ii) quantifying the reduction in computational time required for convergence. It results in a speed-up factor of ∼120 when compared to a fully numeric version, or ∼38, with respect to a more conventional implementation, while converging to very similar values for the estimated model parameters. The proposed method is also tested on dynamic 3D PET clinical data of four control subjects. The results obtained supported those of the simulation study, and provided input and promising perspectives for the application of the proposed technique in clinical practice.

Attenuation correction in 4D-PET using a single-phase attenuation map and rigidity-adaptive deformable registration.

PURPOSE: Four-dimensional positron emission tomography (4D-PET) imaging is a potential solution to the respiratory motion effect in the thoracic region. Computed tomography (CT)-based attenuation correction (AC) is an essential step toward quantitative imaging for PET. However, due to the temporal difference between 4D-PET and a single attenuation map from CT, typically available in routine clinical scanning, motion artifacts are observed in the attenuation-corrected PET images, leading to errors in tumor shape and uptake. We introduced a practical method to align single-phase CT with all other 4D-PET phases for AC. METHODS: A penalized non-rigid Demons registration between individual 4D-PET frames without AC provides the motion vectors to be used for warping single-phase attenuation map. The non-rigid Demons registration was used to derive deformation vector fields (DVFs) between PET matched with the CT phase and other 4D-PET images. While attenuated PET images provide useful data for organ borders such as those of the lung and the liver, tumors cannot be distinguished from the background due to loss of contrast. To preserve the tumor shape in different phases, an ROI-covering tumor was excluded from nonrigid transformation. Instead the mean DVF of the central region of the tumor was assigned to all voxels in the ROI. This process mimics a rigid transformation of the tumor along with a nonrigid transformation of other organs. A 4D-XCAT phantom with spherical lung tumors, with diameters ranging from 10 to 40 mm, was used to evaluate the algorithm. The performance of the proposed hybrid method for attenuation map estimation was compared to (a) the Demons nonrigid registration only and (b) a single attenuation map based on quantitative parameters in individual PET frames. RESULTS: Motion-related artifacts were significantly reduced in the attenuation-corrected 4D-PET images. When a single attenuation map was used for all individual PET frames, the normalized root-mean-square error (NRMSE) values in tumor region were 49.3% (STD: 8.3%), 50.5% (STD: 9.3%), 51.8% (STD: 10.8%) and 51.5% (STD: 12.1%) for 10-mm, 20-mm, 30-mm, and 40-mm tumors, respectively. These errors were reduced to 11.9% (STD: 2.9%), 13.6% (STD: 3.9%), 13.8% (STD: 4.8%), and 16.7% (STD: 9.3%) by our proposed method for deforming the attenuation map. The relative errors in total lesion glycolysis (TLG) values were -0.25% (STD: 2.87%) and 3.19% (STD: 2.35%) for 30-mm and 40-mm tumors, respectively, in proposed method. The corresponding values for Demons method were 25.22% (STD: 14.79%) and 18.42% (STD: 7.06%). Our proposed hybrid method outperforms the Demons method especially for larger tumors. For tumors smaller than 20 mm, nonrigid transformation could also provide quantitative results. CONCLUSION: Although non-AC 4D-PET frames include insignificant anatomical information, they are still useful to estimate the DVFs to align the attenuation map for accurate AC. The proposed hybrid method can recover the AC-related artifacts and provide quantitative AC-PET images.

4-Dimensional MRI and Attenuation Map Generation in PET/MRI with 4-Dimensional PET-Derived Deformation Matrices: Study of Feasibility for Lung Cancer Applications.

Respiratory motion may reduce accuracy in the fusion of functional and anatomic images from combined PET/MRI systems. Methodologies for the correction of respiratory motion in PET acquisitions with such systems are mostly based on the use of respiration-synchronized MRI acquisitions to derive motion fields. Existing approaches based on tagging acquisitions may introduce artifacts in MR images, whereas motion model approaches require the acquisition of training datasets. The objective of this work was to investigate the possibility of generating 4-dimensional (4D) MR images and associated attenuation maps (AMs) from the combination of a single static MR image and motion fields obtained from simultaneously acquired 4D non-attenuation-corrected (NAC) PET images. Methods: Four-dimensional PET/MRI datasets were acquired for 11 patients on a simultaneous PET/MRI system. The 4D PET datasets were retrospectively binned into 4 motion amplitude frames corresponding to the simultaneously acquired T1-weighted 4D MR images. A T1-weighted 3-dimensional MRI sequence with Dixon-based fat and water separation was also acquired at the end of expiration for PET attenuation correction purposes. All reconstructed 4D NAC PET images were then elastically registered to the single end-of-expiration NAC PET image. The derived motion fields were subsequently applied to the end-of-expiration frame of the acquired 4D MRI volume and the AM derived from the Dixon MR image to generate respiration-synchronized MR images and corresponding AMs. Results: The accuracy of the proposed method was assessed by comparing the generated and acquired images according to metrics such as overall correlation coefficients and differences in distances of anatomic landmarks on the generated and acquired MRI datasets. High correlation coefficients (mean ± SD: 0.93 ± 0.03) and small differences (2.69 ± 0.5 mm) were obtained. Moreover, small tissue classification differences (2.23% ± 0.68%) between generated and 4D MRI-extracted AMs were observed. Conclusion: Our results confirm the feasibility of using 4D NAC PET images for accurate PET attenuation correction and respiratory motion correction in PET/MRI, without the need for patient-specific 4D MRI acquisitions.

A novel 3D-printed phantom insert for 4D PET/CT imaging and simultaneous integrated boost radiotherapy.

PURPOSE: To construct a 3D-printed phantom insert designed to mimic the variable PET tracer uptake seen in lung tumor volumes and a matching dosimetric insert to be used in simultaneous integrated boost (SIB) phantom studies, and to evaluate the design through end-to-end tests. METHODS: A set of phantom inserts was designed and manufactured for a realistic representation of gated radiotherapy steps from 4D PET/CT scanning to dose delivery. A cylindrical phantom (φ80 × 120 mm) holds inserts for PET/CT scanning. The novel 3D printed insert dedicated to 4D PET/CT mimics high PET tracer uptake in the core and low uptake in the periphery. This insert is a variable density porous cylinder (φ44.5 × 70.0 mm), ABS-P430 thermoplastic, 3D printed by fused deposition modeling an inner (φ11 × 42 mm) cylindrical void. The square pores (1.8 × 1.8 mm2 each) fill 50% of outer volume, resulting in a 2:1 PET tracer concentration ratio in the void volume with respect to porous volume. A matching cylindrical phantom insert is dedicated to validate gated radiotherapy. It contains eight peripheral holes and one central hole, matching the location of the porous part and the void part of the 3D printed insert, respectively. These holes accommodate adaptors for Farmer-type ion chamber and cells vials. End-to-end tests were designed for imaging, planning, and dose measurements. RESULTS: End-to-end test were performed from 4D PET/CT scanning to transferring data to the planning system, target volume delineation, and dose measurements. 4D PET/CT scans were acquired of the phantom at different respiratory motion patterns and gating windows. A measured 2:1 18F-FDG concentration ratio between inner void and outer porous volume matched the 3D printed design. Measured dose in the dosimetric insert agreed well with planned dose on the imaging insert, within 3% for the static phantom and within 5% for most breathing patterns. CONCLUSIONS: The novel 3D printed phantom insert mimics variable PET tracer uptake typical of tumors. Obtained 4D PET/CT scans are suitable for segmentation and treatment planning and delivery in SIB gated treatments. Our experiments demonstrate the feasibility of this set of phantom inserts serving as end-to-end quality-assurance phantoms of SIB radiotherapy.

First clinical investigation of a 4D maximum likelihood reconstruction for 4D PET-based treatment verification in ion beam therapy.

BACKGROUND AND PURPOSE: In clinical applications of Positron Emission Tomography (PET)-based treatment verification in ion beam therapy (PT-PET), detection and interpretation of inconsistencies between Measured PET and Expected PET are mostly limited by Measured PET noise, due to low count statistics, and by Expected PET bias, especially due to inaccurate washout modelling in off-line implementations. In this work, a recently proposed 4D Maximum Likelihood (ML) reconstruction algorithm which considers Measured PET and Expected PET as two different motion phases of a 4D dataset is assessed on clinical 4D PET-CT datasets acquired after carbon ion therapy. MATERIAL AND METHODS: The 4D ML reconstruction algorithm estimates: (1) Measured PET of enhanced image quality with respect to the conventional Measured PET, thanks to the exploitation of Expected PET; (2) the deformation field mapping the Expected PET onto the Measured PET as a measure of the occurred displacements. RESULTS: Results demonstrate the desired sensitivity to inconsistencies due to breathing motion and/or setup modification, robustness to noise in different count statistics scenarios, but a limited sensitivity to Expected PET washout inaccuracy. CONCLUSIONS: The 4D ML reconstruction algorithm supports clinical 4D PT-PET in ion beam therapy. The limited sensitivity to washout inaccuracy can be detected and potentially overcome.

Comparative evaluation of respiratory-gated and ungated FDG-PET for target volume definition in radiotherapy treatment planning for pancreatic cancer.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of respiratory-gated positron emission tomography (4D-PET) in pancreatic cancer radiotherapy treatment planning (RTTP). MATERIALS AND METHODS: Fourteen patients with 18F-fluorodeoxyglucose (FDG)-avid pancreatic tumours were evaluated between December 2013 and March 2015. Two sets of volumes were contoured for the pancreatic tumour of each patient. The biological target volume in three-dimensional RTTP (BTV3D) was contoured using conventional respiratory un-gated PET. The BTV3D was then expanded using population-based margins to generate a series of internal target volume 3D (ITV3D) values. The ITV 4D (ITV4D) was contoured using 4D-PET. Each of the five phases of 4D-PET was used for 4D contouring, and the ITV4D was constructed by summing the volumes defined on the five individual 4D-PET images. The relative volumes and normalized volumetric overlap were computed between ITV3D and ITV4D. RESULTS: On average, the FDG-avid tumour volumes were 1.6 (range: 0.8-2.3) fold greater in the ITV4D than in the BTV3D. On average, the ITV3D values were 2.0 (range: 1.1-3.4) fold larger than the corresponding ITV4D values. CONCLUSION: The ITV generated from 4D-PET can be used to improve the accuracy or reduce normal tissue irradiation compared with conventional un-gated PET-based ITV.

The impact of audiovisual biofeedback on 4D functional and anatomic imaging: Results of a lung cancer pilot study.

BACKGROUND AND PURPOSE: The impact of audiovisual (AV) biofeedback on four dimensional (4D) positron emission tomography (PET) and 4D computed tomography (CT) image quality was investigated in a prospective clinical trial (NCT01172041). MATERIAL AND METHODS: 4D-PET and 4D-CT images of ten lung cancer patients were acquired with AV biofeedback (AV) and free breathing (FB). The 4D-PET images were analyzed for motion artifacts by comparing 4D to 3D PET for gross tumor volumes (GTVPET) and maximum standardized uptake values (SUVmax). The 4D-CT images were analyzed for artifacts by comparing normalized cross correlation-based scores (NCCS) and quantifying a visual assessment score (VAS). A Wilcoxon signed-ranks test was used for statistical testing. RESULTS: The impact of AV biofeedback varied widely. Overall, the 3D to 4D decrease of GTVPET was 1.2±1.3cm(3) with AV and 0.6±1.8cm(3) for FB. The 4D-PET increase of SUVmax was 1.3±0.9 with AV and 1.3±0.8 for FB. The 4D-CT NCCS were 0.65±0.27 with AV and 0.60±0.32 for FB (p=0.08). The 4D-CT VAS was 0.0±2.7. CONCLUSION: This study demonstrated a high patient dependence on the use of AV biofeedback to reduce motion artifacts in 4D imaging. None of the hypotheses tested were statistically significant. Future development of AV biofeedback will focus on optimizing the human-computer interface and including patient training sessions for improved comprehension and compliance.

A comparative study of the target volume definition in radiotherapy with «Slow CT Scan¼ vs. 4D PET/CT Scan in early stages non-small cell lung cancer. / Estudio comparativo en la definición del volumen de tratamiento en radioterapia con «Slow TC Scan¼ vs. 4D PET/TC Scan en estadios iniciales de cáncer de pulmón de célula no pequeña.

OBJECTIVES: To evaluate the use of 4D PET/CT to quantify tumor respiratory motion compared to the «Slow¼-CT (CTs) in the radiotherapy planning process. MATERIAL AND METHODS: A total of 25 patients with inoperable early stage non small cell lung cancer (NSCLC) were included in the study. Each patient was imaged with a CTs (4s/slice) and 4D PET/CT. The adequacy of each technique for respiratory motion capture was evaluated using the volume definition for each of the following: Internal target volume (ITV) 4D and ITVslow in relation with the volume defined by the encompassing volume of 4D PET/CT and CTs (ITVtotal). The maximum distance between the edges of the volume defined by each technique to that of the total volume was measured in orthogonal beam's eye view. RESULTS: The ITV4D showed less differences in relation with the ITVtotal in both the cranio-caudal and the antero-posterior axis compared to the ITVslow. The maximum differences were 0.36mm in 4D PET/CTand 0.57mm in CTs in the antero-posterior axis. 4D PET/CT resulted in the definition of more accurate (ITV4D/ITVtotal 0.78 vs. ITVs/ITVtotal 0.63), and larger ITVs (19.9 cc vs. 16.3 cc) than those obtained with CTs. CONCLUSION: Planning with 4D PET/CT in comparison with CTs, allows incorporating tumor respiratory motion and improving planning radiotherapy of patients in early stages of lung cancer.

Reconstruction-Incorporated Respiratory Motion Correction in Clinical Simultaneous PET/MR Imaging for Oncology Applications.

UNLABELLED: Simultaneous PET and MR imaging is a promising new technique allowing the fusion of functional (PET) and anatomic/functional (MR) information. In the thoracic-abdominal regions, respiratory motion is a major challenge leading to reduced quantitative and qualitative image accuracy. Correction methodologies include the use of gated frames that lead to low signal-to-noise ratio considering the associated low statistics. More advanced correction approaches, previously developed for PET/CT imaging, consist of either registering all the reconstructed gated frames to the reference frame or incorporating motion parameters into the iterative reconstruction process to produce a single motion-compensated PET image. The goal of this work was to compare these two­previously implemented in PET/CT­correction approaches within the context of PET/MR motion correction for oncology applications using clinical 4-dimensional PET/MR acquisitions. Two different correction approaches were evaluated comparing the incorporation of elastic transformations extracted from 4-dimensional MR imaging datasets during PET list-mode image reconstruction to a postreconstruction image-based approach. METHODS: Eleven patient datasets acquired on a PET/MR system were used. T1-weighted 4D MR images were registered to the end-expiration image using a nonrigid B-spline registration algorithm to derive deformation matrices accounting for respiratory motion. The derived matrices were subsequently incorporated within a PET image reconstruction of the original emission list-mode data (reconstruction space [RS] method). The corrected images were compared with those produced by applying the deformation matrices in the image space (IS method) followed by summing the realigned gated frames, as well as with uncorrected motion-averaged images. RESULTS: Both correction techniques led to significant improvement in accounting for respiratory motion artifacts when compared with uncorrected motion-averaged images. These improvements included signal-to-noise ratio (mean increase of 28.0% and 24.2% for the RS and IS methods, respectively), lesion size (reduction of 60.4% and 47.9%, respectively), lesion contrast (increase of 70.1% and 57.2%, respectively), and lesion position (changes of 60.9% and 46.7%, respectively). CONCLUSION: Our results demonstrate significant respiratory motion compensation using both methods, with superior results from a 4D PET RS approach.

First Steps Toward Ultrasound-Based Motion Compensation for Imaging and Therapy: Calibration with an Optical System and 4D PET Imaging.

Target motion, particularly in the abdomen, due to respiration or patient movement is still a challenge in many diagnostic and therapeutic processes. Hence, methods to detect and compensate this motion are required. Diagnostic ultrasound (US) represents a non-invasive and dose-free alternative to fluoroscopy, providing more information about internal target motion than respiration belt or optical tracking. The goal of this project is to develop an US-based motion tracking for real-time motion correction in radiation therapy and diagnostic imaging, notably in 4D positron emission tomography (PET). In this work, a workflow is established to enable the transformation of US tracking data to the coordinates of the treatment delivery or imaging system - even if the US probe is moving due to respiration. It is shown that the US tracking signal is equally adequate for 4D PET image reconstruction as the clinically used respiration belt and provides additional opportunities in this concern. Furthermore, it is demonstrated that the US probe being within the PET field of view generally has no relevant influence on the image quality. The accuracy and precision of all the steps in the calibration workflow for US tracking-based 4D PET imaging are found to be in an acceptable range for clinical implementation. Eventually, we show in vitro that an US-based motion tracking in absolute room coordinates with a moving US transducer is feasible.

Optimized PET imaging for 4D treatment planning in radiotherapy: the virtual 4D PET strategy.

The purpose of the study is to evaluate the performance of a novel strategy, referred to as "virtual 4D PET", aiming at the optimization of hybrid 4D CT-PET scan for radiotherapy treatment planning. The virtual 4D PET strategy applies 4D CT motion modeling to avoid time-resolved PET image acquisition. This leads to a reduction of radioactive tracer administered to the patient and to a total acquisition time comparable to free-breathing PET studies. The proposed method exploits a motion model derived from 4D CT, which is applied to the free-breathing PET to recover respiratory motion and motion blur. The free-breathing PET is warped according to the motion model, in order to generate the virtual 4D PET. The virtual 4D PET strategy was tested on images obtained from a 4D computational anthropomorphic phantom. The performance was compared to conventional motion compensated 4D PET. Tests were also carried out on clinical 4D CT-PET scans coming from seven lung and liver cancer patients. The virtual 4D PET strategy was able to recover lesion motion, with comparable performance with respect to the motion compensated 4D PET. The compensation of the activity blurring due to motion was successfully achieved in terms of spill out removal. Specific limitations were highlighted in terms of partial volume compensation. Results on clinical 4D CT-PET scans confirmed the efficacy in 4D PET count statistics optimization, as equal to the free-breathing PET, and recovery of lesion motion. Compared to conventional motion compensation strategies that explicitly require 4D PET imaging, the virtual 4D PET strategy reduces clinical workload and computational costs, resulting in significant advantages for radiotherapy treatment planning.

Motion-specific internal target volumes for FDG-avid mediastinal and hilar lymph nodes.

BACKGROUND AND PURPOSE: To quantify the benefit of motion-specific internal target volumes for FDG-avid mediastinal and hilar lymph nodes generated using 4D-PET, vs. conventional internal target volumes generated using non-respiratory gated PET and 4D-CT scans. MATERIALS AND METHODS: Five patients with FDG-avid tumors metastatic to 11 hilar or mediastinal lymph nodes were imaged with respiratory-correlated FDG-PET (4D-PET) and 4D-CT. FDG-avid nodes were contoured by a radiation oncologist in two ways. Standard-of-care volumes were contoured using conventional un-gated PET, 4D-CT, and breath-hold CT. A second, motion-specific, set of volumes were contoured using 4D-PET.Contours based on 4D-PET corresponded directly to an internal target volume (ITV(4D)), whereas contours based on un-gated PET were expanded by a series of exploratory isotropic margins (from 5 to 13 mm) based on literature recommendations on lymph node motion to form internal target volumes (ITV(3D)). RESULTS: A 13 mm expansion of the un-gated PET nodal volume was needed to cover the ITV(4D) for 10 of 11 nodes studied. The ITV(3D) based on a 13 mm expansion included on average 45 cm(3) of tissue that was not included in the ITV(4D). CONCLUSIONS: Motion-specific lymph-node internal target volumes generated from 4D-PET imaging could be used to improve accuracy and/or reduce normal-tissue irradiation compared to the standard-of-care un-gated PET based internal target volumes.