Nuclear imaging for improved radioembolization treatment planning

Radioembolization is a minimally invasive treatment for liver cancer. During a radioembolization procedure small radioactive spheres (microspheres) are administered in the vasculature of the liver. These microspheres lodge (mostly) in the tumorous tissue, where they locally irradiate liver tumours, whilst (mostly) sparing the healthy liver tissue. Prior to the treatment procedure, a pre-treatment safety procedure is performed in which surrogate particles, technetium-99m labelled macroaggregated albumin (99mTc-MAA), are administered to simulate the distribution of the microspheres. These 99mTc-MAA particles are visualised using nuclear imaging. Based on the amount of 99mTc-MAA shunting to the lungs (lung shunt fraction), the unwanted accumulation of 99mTc-MAA elsewhere outside the liver (extrahepatic depositions), and the distribution of 99mTc-MAA within the liver (intrahepatic dose distribution), a nuclear medicine physician decides whether or not it is safe to proceed with the treatment procedure. When considered safe, the treatment will usually take place 1-2 weeks later. The microspheres that are administered during the radioembolization treatment have a certain level of radioactivity, measured in becquerel (Bq). Deciding where and how much activity needs to be administered for treatment is called treatment planning. The calculation of the amount of activity that needs to be administered is based on physical models, but these are generally not tailored to individual patients. This thesis introduced several ways to improve radioembolization treatment planning using nuclear imaging

Accelerated SPECT image reconstruction with FBP and an image enhancement convolutional neural network

BACKGROUND: Monte Carlo-based iterative reconstruction to correct for photon scatter and collimator effects has been proven to be superior over analytical correction schemes in single-photon emission computed tomography (SPECT/CT), but it is currently not commonly used in daily clinical practice due to the long associated reconstruction times. We propose to use a convolutional neural network (CNN) to upgrade fast filtered back projection (FBP) image quality so that reconstructions comparable in quality to the Monte Carlo-based reconstruction can be obtained within seconds. RESULTS: A total of 128 technetium-99m macroaggregated albumin pre-treatment SPECT/CT scans used to guide hepatic radioembolization were available. Four reconstruction methods were compared: FBP, clinical reconstruction, Monte Carlo-based reconstruction, and the neural network approach. The CNN generated reconstructions in 5 sec, whereas clinical reconstruction took 5 min and the Monte Carlo-based reconstruction took 19 min. The mean squared error of the neural network approach in the validation set was between that of the Monte Carlo-based and clinical reconstruction, and the lung shunting fraction difference was lower than 2 percent point. A phantom experiment showed that quantitative measures required in radioembolization were accurately retrieved from the CNN-generated reconstructions. CONCLUSIONS: FBP with an image enhancement neural network provides SPECT reconstructions with quality close to that obtained with Monte Carlo-based reconstruction within seconds

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

Performance of a dual-layer scanner for hybrid SPECT/CBCT

Fluoroscopic procedures involving radionuclides would benefit from interventional nuclear imaging by obtaining real-time feedback on the activity distribution. We have previously proposed a dual-layer detector that offers such procedural guidance by simultaneous fluoroscopic and nuclear planar imaging. Acquisition of single photon computed tomography (SPECT) and cone beam computed tomography (CBCT) could provide additional information on the activity distribution. This study investigates the feasibility and the image quality of simultaneous SPECT/CBCT, by means of phantom experiments and simulations. Simulations were performed to study the obtained reconstruction quality for (i) clinical SPECT/CT, (ii) a dual-layer scanner configured with optimized hardware, and (iii) our (non-optimized) dual-layer prototype. Experiments on an image quality phantom and an anthropomorphic phantom (including extrahepatic depositions with volumes and activities close to the median values encountered in hepatic radioembolization) were performed with a clinical SPECT/CT scanner and with our dual-layer prototype. Nuclear images were visually and quantitatively evaluated by measuring the tumor/non-tumor (T/N) ratio and contrast-to-noise ratio (CNR). The simulations showed that the maximum obtained CNR was 38.8 ± 0.8 for the clinical scanner, 30.2 ± 0.9 for the optimized dual-layer scanner, and 20.8 ± 0.4 for the prototype scanner. T/N ratio showed a similar decline. The phantom experiments showed that performing simultaneous SPECT/CBCT is feasible. The CNR obtained from the SPECT reconstruction of largest sphere in the image quality phantom was 43.1 for the clinical scanner and 28.6 for the developed prototype scanner. The anthropomorphic phantom showed that the extrahepatic depositions were detected with both scanners. A dual-layer detector is able to simultaneously acquire SPECT and CBCT. Both CNR and T/N ratio are worse than that of a clinical system, but the phantom experiments showed that extrahepatic depositions with volumes and activities close to the median values encountered in hepatic radioembolization could be distinguished

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