Current Status and Future Direction of Hepatic Radioembolisation.

Radioembolisation is a locoregional treatment modality for hepatic malignancies. It consists of several stages that are vital to its success, which include a pre-treatment angiographic simulation followed by nuclear medicine imaging, treatment activity choice, treatment procedure and post-treatment imaging. All these stages have seen much advancement over the past decade. Here we aim to provide an overview of the practice of radioembolisation, discuss the limitations of currently applied methods and explore promising developments

Impact of Respiratory Motion and Acquisition Settings on SPECT Liver Dosimetry for Radioembolization

PURPOSE: Respiratory motion may impose significant inaccuracies on emission activity estimation in quantitative SPECT. This effect may be a major issue in dosimetry as used in management of liver radioembolization. The purpose of this study was to investigate the impact of respiratory motion on radioembolization liver dosimetry for different SPECT acquisition settings. METHODS: In a series of SPECT/CT Monte Carlo simulations using several digital XCAT phantoms, the following parameters were varied: breathing/non-breathing, liver tumor size (0.3 - 35 ml) and location, patient properties (body mass index ranging from underweight to obese; male and female), acquisition time (10 - 30 seconds/view), collimator setup (High Sensitivity, High Resolution, Ultra High Resolution), tumor VOI. The effect of applying a respiratory gating scheme was examined as well. RESULTS: Breathing decreased activity recovery and tumor/non-tumor (T/N) ratios on average from 90% to 66%. VOIs based on SPECT images instead of breath-hold CT improved T/N values significantly. The most accurate results were obtained using a gating scheme combined with SPECT-based VOIs. Scan duration, body mass index, sex and location all had a minor effect. Lung shunt fraction estimations were relatively unaffected by any of the varied parameters. CONCLUSIONS: Respiratory motion has a large effect on SPECT activity quantitation of liver tumors as used in radioembolization treatment planning and assessment. As compared with the other parameters that were varied in this study, respiration is the predominant degrading effect on image quantitation. Gating alleviates much of this detrimental effect. This article is protected by copyright. All rights reserved

Fast and accurate quantitative determination of the lung shunt fraction in hepatic radioembolization

Radioembolization treatment is preceded by a 99mTc-MAA safety procedure, which is used to estimate the lung shunt fraction (LSF). Normally, the LSF is estimated by using the geometric mean of planar scintigraphy (PS-GM). However, concern has been raised about the potential overestimation of the LSF by PS-GM. Alternatively, SPECT/CT may be used for LSF estimation, but requires lengthy acquisitions, 3D segmentation, and has a limited field of view, which calls for extrapolation of the reconstructed lung counts, which introduces another source of error. We have developed a simplified SPECT/CT protocol for LSF estimation, called the quantitative orthogonal planar (QOP) method that requires only four projections to quantitatively reconstruct liver and lung activity. This mitigates the problems associated with LSF estimations from SPECT/CT. The purpose of this study was to introduce and evaluate QOP by comparing its performance to PS-GM and SPECT/CT in a retrospective patient study, and by supporting simulation experiments. Patients who received at least one 99mTc-MAA safety procedure in our center were included in this study. QOP and PS-GM were compared to SPECT/CT in Bland-Altman analyses. Supporting digital phantom experiments with a known ground-truth were performed to evaluate the performance of this method. Analysis of PS-GM versus SPECT/CT LSF estimates revealed both a larger imprecision and significant bias by PS-GM (limits of agreement: 8.1 percentage points (pp); bias: 2.7 pp). The QOP method agreed better with the SPECT/CT-based estimation (limits of agreement: 2.07 pp; bias: 0.52 pp). This observation was consistent with the digital phantom experiments. We have proposed and evaluated a novel method called QOP for LSF estimation that performs almost as accurate as SPECT/CT, but without the need for lung mass extrapolation, long scan duration, or extensive manual segmentation, making it as fast as current PS-GM

Respiratory motion compensation in interventional liver SPECT using simultaneous fluoroscopic and nuclear imaging

Purpose: Quantitative accuracy of the single photon emission computed tomography (SPECT) reconstruction of the pretreatment procedure of liver radioembolization is crucial for dosimetry; visual quality is important for detecting doses deposited outside the planned treatment volume. Quantitative accuracy is limited by respiratory motion. Conventional gating eliminates motion by count rejection but increases noise, which degrades the visual reconstruction quality. Motion compensation using all counts can be performed if the motion signal and motion vector field over time are known. The measurement of the motion signal of a patient currently requires a device (such as a respiratory belt) attached to the patient, which complicates the acquisition. The motion vector field is generally extracted from a previously acquired four-dimensional scan and can differ from the motion in the scan performed during the intervention. The simultaneous acquisition of fluoroscopic and nuclear projections can be used to obtain both the motion vector field and the projections of the corresponding (moving) activity distribution. This eliminates the need for devices attached to the patient and provides an accurate motion vector field for SPECT reconstruction. Our approach to motion compensation would primarily be beneficial for interventional SPECT because the time-critical setting requires fast scans and no inconvenience of an external apparatus. The purpose of this work is to evaluate the performance of the motion compensation approach for interventional liver SPECT by means of simulations. Methods: Nuclear and fluoroscopic projections of a realistic digital human phantom with respiratory motion were generated using fast Monte Carlo simulators. Fluoroscopic projections were sampled at 1–5 Hz. Nuclear data were acquired continuously in list mode. The motion signal was extracted from the fluoroscopic projections by calculating the center-of-mass, which was then used to assign each photon to a corresponding motion bin. The fluoroscopic projections were reconstructed per bin and coregistered, resulting in a motion vector field that was used in the SPECT reconstruction. The influence of breathing patterns, fluoroscopic imaging dose, sampling rate, number of bins, and scanning time was studied. In addition, the motion compensation method was compared with conventional gating to evaluate the detectability of spheres with varying uptake ratios. Results: The liver motion signal was accurately extracted from the fluoroscopic projections, provided the motion was stable in amplitude and the sampling rate was greater than 2 Hz. The minimum total fluoroscopic dose for the proposed method to function in a 5-min scan was 10 µGy. Although conventional gating improved the quantitative reconstruction accuracy, substantial background noise was observed in the short scans because of the limited counts available. The proposed method similarly improved the quantitative accuracy, but generated reconstructions with higher visual quality. The proposed method provided better visualization of low-contrast features than when using gating. Conclusion: The proposed motion compensation method has the potential to improve SPECT reconstruction quality. The method eliminates the need for external devices to measure the motion signal and generates an accurate motion vector field for reconstruction. A minimal increase in the fluoroscopic dose is required to substantially improve the results, paving the way for clinical use

Respiratory motion compensation in interventional liver SPECT using simultaneous fluoroscopic and nuclear imaging

Purpose: Quantitative accuracy of the single photon emission computed tomography (SPECT) reconstruction of the pretreatment procedure of liver radioembolization is crucial for dosimetry; visual quality is important for detecting doses deposited outside the planned treatment volume. Quantitative accuracy is limited by respiratory motion. Conventional gating eliminates motion by count rejection but increases noise, which degrades the visual reconstruction quality. Motion compensation using all counts can be performed if the motion signal and motion vector field over time are known. The measurement of the motion signal of a patient currently requires a device (such as a respiratory belt) attached to the patient, which complicates the acquisition. The motion vector field is generally extracted from a previously acquired four-dimensional scan and can differ from the motion in the scan performed during the intervention. The simultaneous acquisition of fluoroscopic and nuclear projections can be used to obtain both the motion vector field and the projections of the corresponding (moving) activity distribution. This eliminates the need for devices attached to the patient and provides an accurate motion vector field for SPECT reconstruction. Our approach to motion compensation would primarily be beneficial for interventional SPECT because the time-critical setting requires fast scans and no inconvenience of an external apparatus. The purpose of this work is to evaluate the performance of the motion compensation approach for interventional liver SPECT by means of simulations. Methods: Nuclear and fluoroscopic projections of a realistic digital human phantom with respiratory motion were generated using fast Monte Carlo simulators. Fluoroscopic projections were sampled at 1–5 Hz. Nuclear data were acquired continuously in list mode. The motion signal was extracted from the fluoroscopic projections by calculating the center-of-mass, which was then used to assign each photon to a corresponding motion bin. The fluoroscopic projections were reconstructed per bin and coregistered, resulting in a motion vector field that was used in the SPECT reconstruction. The influence of breathing patterns, fluoroscopic imaging dose, sampling rate, number of bins, and scanning time was studied. In addition, the motion compensation method was compared with conventional gating to evaluate the detectability of spheres with varying uptake ratios. Results: The liver motion signal was accurately extracted from the fluoroscopic projections, provided the motion was stable in amplitude and the sampling rate was greater than 2 Hz. The minimum total fluoroscopic dose for the proposed method to function in a 5-min scan was 10 µGy. Although conventional gating improved the quantitative reconstruction accuracy, substantial background noise was observed in the short scans because of the limited counts available. The proposed method similarly improved the quantitative accuracy, but generated reconstructions with higher visual quality. The proposed method provided better visualization of low-contrast features than when using gating. Conclusion: The proposed motion compensation method has the potential to improve SPECT reconstruction quality. The method eliminates the need for external devices to measure the motion signal and generates an accurate motion vector field for reconstruction. A minimal increase in the fluoroscopic dose is required to substantially improve the results, paving the way for clinical use

Radioembolization lung shunt estimation based on a 90Y pre-treatment procedure : a phantom study

PURPOSE: Prior to 90 Y radioembolization, a pre-treatment procedure is performed, in which 99m Tc-macroaggerated albumin (99m Tc-MAA) is administered to estimate the amount of activity shunting to the lungs. A high lung shunt fraction (LSF) may impose lower prescribed treatment activity or even impede treatment. Accurate LSF measurement is therefore important, but is hampered by the use of MAA particles, which differ from 90 Y microspheres. Ideally, 90 Y microspheres would also be used for the pre-treatment procedure, but this would require the activity to be lower than an estimated safety threshold of about 100 MBq to avoid unintended radiation damage. However, 90 Y is very challenging to image, especially at low activities (<100 MBq). The purpose of this study was to evaluate the performance of three nuclear imaging techniques in estimating the LSF in a low activity 90 Y pre-treatment scan, using an anthropomorphic phantom: (i) positron emission tomography/computed tomography (PET/CT), (ii) Bremsstrahlung single photon emission tomography/computed tomography (SPECT/CT), and (iii) planar imaging. METHODS: The lungs and liver of an anthropomorphic phantom were filled with 90 Y chloride to acquire an LSF of 15%. Several PET/CT (Siemens Biograph mCT), Bremsstrahlung SPECT/CT (Siemens Symbia T16) and planar images (Siemens Symbia T16) were acquired at a range of 90 Y activities (1586 MBq down to 25 MBq). PET images were reconstructed using a clinical protocol (attenuation correction, TOF, scatter and random correction, OP-OSEM), SPECT images were reconstructed using both a clinical protocol (attenuation correction, OSEM) and a Monte Carlo (MC) based reconstruction method (MC-based detector, scatter, and attenuation modeling, OSEM), for planar images the geometric mean was calculated. In addition, in all cases except clinical SPECT, background correction was included. The LSF was calculated by assessing the reconstructed activity in the lungs and in the liver, as delineated on the CT images. In addition to the 15% LSF, an extra 'cold' region was included to simulate an LSF of 0%. RESULTS: PET reconstructions accurately estimated the LSF (absolute difference <2 percent point (pp)) when total activity was over 200 MBq, but greatly overestimated the LSF (up to 25pp) when activity decreased. Bremsstrahlung SPECT clinical reconstructions overestimated the LSF (up to 13pp) when activity was both high and low. Similarly, planar images overestimated the LSF (up to 23pp). MC-based SPECT reconstructions accurately estimated the LSF with an absolute difference of less than 1.3pp for activities as low as 70 MBq. CONCLUSIONS: Bremsstrahlung SPECT/CT can accurately estimate the LSF for a 90 Y pre-treatment procedure using a theoretically safe 90 Y activity as low as 70 MBq, when reconstructed with an MC-based model. This article is protected by copyright. All rights reserved

Radioembolization lung shunt estimation based on a 90Y pre-treatment procedure : a phantom study

PURPOSE: Prior to 90 Y radioembolization, a pre-treatment procedure is performed, in which 99m Tc-macroaggerated albumin (99m Tc-MAA) is administered to estimate the amount of activity shunting to the lungs. A high lung shunt fraction (LSF) may impose lower prescribed treatment activity or even impede treatment. Accurate LSF measurement is therefore important, but is hampered by the use of MAA particles, which differ from 90 Y microspheres. Ideally, 90 Y microspheres would also be used for the pre-treatment procedure, but this would require the activity to be lower than an estimated safety threshold of about 100 MBq to avoid unintended radiation damage. However, 90 Y is very challenging to image, especially at low activities (<100 MBq). The purpose of this study was to evaluate the performance of three nuclear imaging techniques in estimating the LSF in a low activity 90 Y pre-treatment scan, using an anthropomorphic phantom: (i) positron emission tomography/computed tomography (PET/CT), (ii) Bremsstrahlung single photon emission tomography/computed tomography (SPECT/CT), and (iii) planar imaging. METHODS: The lungs and liver of an anthropomorphic phantom were filled with 90 Y chloride to acquire an LSF of 15%. Several PET/CT (Siemens Biograph mCT), Bremsstrahlung SPECT/CT (Siemens Symbia T16) and planar images (Siemens Symbia T16) were acquired at a range of 90 Y activities (1586 MBq down to 25 MBq). PET images were reconstructed using a clinical protocol (attenuation correction, TOF, scatter and random correction, OP-OSEM), SPECT images were reconstructed using both a clinical protocol (attenuation correction, OSEM) and a Monte Carlo (MC) based reconstruction method (MC-based detector, scatter, and attenuation modeling, OSEM), for planar images the geometric mean was calculated. In addition, in all cases except clinical SPECT, background correction was included. The LSF was calculated by assessing the reconstructed activity in the lungs and in the liver, as delineated on the CT images. In addition to the 15% LSF, an extra 'cold' region was included to simulate an LSF of 0%. RESULTS: PET reconstructions accurately estimated the LSF (absolute difference <2 percent point (pp)) when total activity was over 200 MBq, but greatly overestimated the LSF (up to 25pp) when activity decreased. Bremsstrahlung SPECT clinical reconstructions overestimated the LSF (up to 13pp) when activity was both high and low. Similarly, planar images overestimated the LSF (up to 23pp). MC-based SPECT reconstructions accurately estimated the LSF with an absolute difference of less than 1.3pp for activities as low as 70 MBq. CONCLUSIONS: Bremsstrahlung SPECT/CT can accurately estimate the LSF for a 90 Y pre-treatment procedure using a theoretically safe 90 Y activity as low as 70 MBq, when reconstructed with an MC-based model. This article is protected by copyright. All rights reserved

The physics of radioembolization

Abstract Radioembolization is an established treatment for chemoresistant and unresectable liver cancers. Currently, treatment planning is often based on semi-empirical methods, which yield acceptable toxicity profiles and have enabled the large-scale application in a palliative setting. However, recently, five large randomized controlled trials using resin microspheres failed to demonstrate a significant improvement in either progression-free survival or overall survival in both hepatocellular carcinoma and metastatic colorectal cancer. One reason for this might be that the activity prescription methods used in these studies are suboptimal for many patients. In this review, the current dosimetric methods and their caveats are evaluated. Furthermore, the current state-of-the-art of image-guided dosimetry and advanced radiobiological modeling is reviewed from a physics’ perspective. The current literature is explored for the observation of robust dose-response relationships followed by an overview of recent advancements in quantitative image reconstruction in relation to image-guided dosimetry. This review is concluded with a discussion on areas where further research is necessary in order to arrive at a personalized treatment method that provides optimal tumor control and is clinically feasible