Comparison of 3 Different Therapeutic Particles in Radioembolization of Locally Advanced Intrahepatic Cholangiocarcinoma.

Our objective was to compare 3 different therapeutic particles used for radioembolization in locally advanced intrahepatic cholangiocarcinoma. Methods: 90Y-glass, 90Y-resin, and 166Ho-labeled poly(l-lactic acid) microsphere prescribed activity was calculated as per manufacturer recommendations. Posttreatment quantitative 90Y PET/CT and quantitative 166Ho SPECT/CT were used to determine tumor-absorbed dose, whole-normal-liver-absorbed dose, treated-normal-liver-absorbed dose, tumor-to-nontumor ratio, lung-absorbed dose, and lung shunt fraction. Response was assessed using RECIST 1.1 and the [18F]FDG PET-based change in total lesion glycolysis. Hepatotoxicity was assessed using the radioembolization-induced liver disease classification. Results: Six 90Y-glass, 8 90Y-resin, and 7 166Ho microsphere patients were included for analysis. The mean administered activity was 2.6 GBq for 90Y-glass, 1.5 GBq for 90Y-resin, and 7.0 GBq for 166Ho microspheres. Tumor-absorbed dose and treated-normal-liver-absorbed dose were significantly higher for 90Y-glass than for 90Y-resin and 166Ho microspheres (mean tumor-absorbed dose, 197 Gy for 90Y-glass vs. 73 Gy for 90Y-resin and 50 Gy for 166Ho; mean treated-normal-liver-absorbed dose, 79 Gy for 90Y-glass vs. 37 Gy for 90Y-resin and 31 Gy for 166Ho). The whole-normal-liver-absorbed dose and tumor-to-nontumor ratio did not significantly differ between the particles. All patients had a lung-absorbed dose under 30 Gy and a lung shunt fraction under 20%. The 3 groups showed similar toxicity and response according to RECIST 1.1 and [18F]FDG PET-based total lesion glycolysis changes. Conclusion: The therapeutic particles used for radioembolization differed from each other and showed significant differences in absorbed dose, whereas toxicity and response were similar for all groups. This finding emphasizes the need for separate dose constraints and dose targets for each particle.

Corrigendum to "Evaluation of image-guided and surface-guided radiotherapy for breast cancer patients treated in deep inspiration breath-hold: A single institution experience" [Tech. Innov. Patient Support Radiat. Oncol. 21 (2022) 51-57].

[This corrects the article DOI: 10.1016/j.tipsro.2022.02.001.].

Evaluation of image-guided and surface-guided radiotherapy for breast cancer patients treated in deep inspiration breath-hold: A single institution experience.

INTRODUCTION: Nowadays, deep inspiratory breath-hold is a common technique to reduce heart dose in left-sided breast radiotherapy. This study evaluates the evolution of the breath-hold technique in our institute, from portal imaging during dose delivery to continuous monitoring with surface-guided radiotherapy (SGRT). MATERIALS AND METHODS: Setup data and portal imaging results were analyzed for 98 patients treated before 2014, and SGRT data for 228 patients treated between 2018 and 2020. For the pre-SGRT group, systematic and random setup errors were calculated for different correction protocols. Residual errors and reproducibility of breath-holds were evaluated for both groups. The benefit of using SGRT for initial positioning was evaluated for another cohort of 47 patients. RESULTS: Online correction reduced the population mean error from 3.9 mm (no corrections) to 1.4 mm. Despite online setup correction, deviations greater than 3 mm were observed in about 10% and 20% of the treatment beams in ventral-dorsal and cranial-caudal directions, respectively. However, these percentages were much smaller than with offline protocols or no corrections. Mean absolute differences between breath-holds within a fraction were smaller in the SGRT-group (1.69 mm) than in the pre-SGRT-group (2.10 mm), and further improved with addition of visual feedback (1.30 mm). SGRT for positioning did not improve setup accuracy, but slightly reduced the time for imaging and setup correction, allowing completion within 3.5 min for 95% of fractions. CONCLUSION: For accurate radiotherapy breast treatments using deep inspiration breath-hold, daily imaging and correction is required. SGRT provides accurate information on patient positioning during treatment and improves patient compliance with visual feedback.

A compact and mobile hybrid C-arm scanner for simultaneous nuclear and fluoroscopic image guidance.

PURPOSE: This study evaluates the performance of a mobile and compact hybrid C-arm scanner (referred to as IXSI) that is capable of simultaneous acquisition of 2D fluoroscopic and nuclear projections and 3D image reconstruction in the intervention room. RESULTS: The impact of slightly misaligning the IXSI modalities (in an off-focus geometry) was investigated for the reduction of the fluoroscopic and nuclear interference. The 2D and 3D nuclear image quality of IXSI was compared with a clinical SPECT/CT scanner by determining the spatial resolution and sensitivity of point sources and by performing a quantitative analysis of the reconstructed NEMA image quality phantom. The 2D and 3D fluoroscopic image of IXSI was compared with a clinical CBCT scanner by visualizing the Fluorad A+D image quality phantom and by visualizing a reconstructed liver nodule phantom. Finally, the feasibility of dynamic simultaneous nuclear and fluoroscopic imaging was demonstrated by injecting an anthropomorphic phantom with a mixture of iodinated contrast and 99mTc. CONCLUSION: Due to the divergent innovative hybrid design of IXSI, concessions were made to the nuclear and fluoroscopic image qualities. Nevertheless, IXSI realizes unique image guidance that may be beneficial for several types of procedures. KEY POINTS: • IXSI can perform time-resolved planar (2D) simultaneous fluoroscopic and nuclear imaging. • IXSI can perform SPECT/CBCT imaging (3D) inside the intervention room.

Dose-Response and Dose-Toxicity Relationships for Glass 90Y Radioembolization in Patients with Liver Metastases from Colorectal Cancer.

Radioembolization based on personalized treatment planning requires established dose-response and dose-toxicity relationships. The aim of this study was to investigate dose-response and dose-toxicity relationships in patients with colorectal liver metastases (CRLMs) treated with glass 90Y-microspheres. Methods: All CRLM patients treated with glass 90Y-microspheres in our institution were retrospectively analyzed. The tumor-absorbed dose was calculated for each measurable metastasis (i.e.,18F-FDG-positive and more than a 5-cm3 tumor volume) on posttreatment 90Y PET. Metabolic tumor response was determined on 18F-FDG PET/CT by measuring the total lesion glycolysis at baseline and at 3 mo after treatment. The relationship between tumor-absorbed dose and metabolic response was determined on a per-lesion and per-patient basis using a linear mixed-effects regression model. Clinical toxicity and laboratory toxicity were correlated with healthy liver-absorbed dose. Results: Thirty-one patients were included. The median tumor-absorbed dose of 85 measurable metastases was 133 Gy (range, 20-1001 Gy). Per response category, this was 196 Gy for complete response (CR), 177 Gy for partial response (PR), 72 Gy for stable disease, and 95 Gy for progressive disease (PD). A significant dose-response relationship was found on a tumor level, with a significantly higher tumor-absorbed dose in metastases with CR (+94%) and PR (+74%) than in metastases with PD (P < 0.001). A similar relationship was found on a patient level, with PR having a higher tumor-absorbed dose than did PD (+58%, P = 0.044). A tumor-absorbed dose of more than 139 Gy predicted a 3-mo metabolic response with the greatest accuracy (89% specificity and 77% sensitivity), whereas a tumor-absorbed dose of more than 189 Gy predicted response with 97% specificity and 45% sensitivity. The median healthy liver-absorbed dose was 63 Gy (range, 24-113 Gy). Toxicity was limited mostly to grades 1 and 2, with 1 case of radioembolization-induced liver disease in a patient who received the highest healthy liver-absorbed dose. A positive trend was seen for most laboratory parameters in our dose-toxicity analysis. Conclusion: A significant relationship was observed between dose and response in CRLM patients treated with glass 90Y radioembolization.

Interventional respiratory motion compensation by simultaneous fluoroscopic and nuclear imaging: a phantom study.

PURPOSE: A compact and mobile hybrid c-arm scanner, capable of simultaneously acquiring nuclear and fluoroscopic projections and SPECT/CBCT, was developed to aid fluoroscopy-guided interventional procedures involving the administration of radionuclides (e.g. hepatic radioembolization). However, as in conventional SPECT/CT, the acquired nuclear images may be deteriorated by patient respiratory motion. We propose to perform compensation for respiratory motion by extracting the motion signal from fluoroscopic projections so that the nuclear counts can be gated into motion bins. The purpose of this study is to quantify the performance of this motion compensation technique with phantom experiments. METHODS: Anthropomorphic phantom configurations that are representative of distributions obtained during the pre-treatment procedure of hepatic radioembolization were placed on a stage that translated with three different motion patterns. Fluoroscopic projections and nuclear counts were simultaneously acquired under planar and SPECT/CBCT imaging. The planar projections were visually assessed. The SPECT reconstructions were visually assessed and quantitatively assessed by calculating the activity recovery of the spherical inserts in the phantom. RESULTS: The planar nuclear projections of the translating anthropomorphic phantom were blurry when no motion compensation was applied. With motion compensation, the nuclear projections became representative of the stationary phantom nuclear projection. Similar behavior was observed for the visual quality of SPECT reconstructions. The mean error of the activity recovery in the uncompensated SPECT reconstructions was 15.8% ± 0.9% for stable motion, 11.9% ± 0.9% for small variations, and 11.0% ± 0.9% for large variations. When applying motion compensation, the mean error decreased to 1.8% ± 1.6% for stable motion, 2.2% ± 1.5% for small variations, and 5.2% ± 2.5% for large variations. CONCLUSION: A compact and mobile hybrid c-arm scanner, capable of simultaneously acquiring nuclear and fluoroscopic projections, can perform compensation for respiratory motion. Such motion compensation results in sharper planar nuclear projections and increases the quantitative accuracy of the SPECT reconstructions.

Monte Carlo-based scatter correction for the SMARTZOOM collimator.

BACKGROUND: Myocardial perfusion imaging is a commonly performed SPECT protocol and hence it would be beneficial if its scan duration could be shortened. For traditional gamma cameras, two developments have separately shown to allow for a shortened scan duration: (i) reconstructing with Monte Carlo-based scatter correction instead of dual-energy window scatter correction and (ii) acquiring projections with the SMARTZOOM collimator instead of a parallel-hole collimator. This study investigates which reduction in scan duration can be achieved when both methods are combined in a single system. RESULTS: The SMARTZOOM collimator was implemented in a Monte Carlo-based reconstruction package and the implementation was validated through image quality phantom experiments. The potential for scan duration reduction was evaluated with a phantom configuration that is realistic for myocardial perfusion imaging. The original reconstruction quality was achieved in 76 ± 8% of the original scan duration when switching from dual-energy window scatter correction to Monte Carlo-based scatter correction. The original reconstruction quality was achieved in 56 ± 13% of the original scan duration when switching from the parallel-hole to the SMARTZOOM collimator. After combining both methods in a single system, the original reconstruction quality was achieved in 34 ± 7% of the original scan duration. CONCLUSIONS: Monte Carlo-based scatter correction combined with the SMARTZOOM collimator can further decrease the scan duration in myocardial perfusion imaging.

Comparison of the Biograph Vision and Biograph mCT for quantitative 90Y PET/CT imaging for radioembolisation.

BACKGROUND: New digital PET scanners with improved time of flight timing and extended axial field of view such as the Siemens Biograph Vision have come on the market and are expected to replace current generation photomultiplier tube (PMT)-based systems such as the Siemens Biograph mCT. These replacements warrant a direct comparison between the systems, so that a smooth transition in clinical practice and research is guaranteed, especially when quantitative values are used for dosimetry-based treatment guidance. The new generation digital PET scanners offer increased sensitivity. This could particularly benefit 90Y imaging, which tends to be very noisy owing to the small positron branching ratio and high random fraction of 90Y. This study aims to determine the ideal reconstruction settings for the digital Vision for quantitative 90Y imaging and to evaluate the image quality and quantification of the digital Vision in comparison with its predecessor, the PMT-based mCT, for 90Y imaging in radioembolisation procedures. METHODS: The NEMA image quality phantom was scanned to determine the ideal reconstruction settings for the Vision. In addition, an anthropomorphic phantom was scanned with both the Vision and the mCT, mimicking a radioembolisation patient with lung, liver, tumour, and extrahepatic deposition inserts. Image quantification of the anthropomorphic phantom was assessed by the lung shunt fraction, the tumour to non-tumour ratio, the parenchymal dose, and the contrast to noise ratio of extrahepatic depositions. RESULTS: For the Vision, a reconstruction with 3 iterations, 5 subsets, and no post-reconstruction filter is recommended for quantitative 90Y imaging, based on the convergence of the recovery coefficient. Comparing both systems showed that the noise level of the Vision is significantly lower than that of the mCT (background variability of 14% for the Vision and 25% for the mCT at 2.5·103 MBq for the 37 mm sphere size). For quantitative 90Y measures, such as needed in radioembolisation, both systems perform similarly. CONCLUSIONS: We recommend to reconstruct 90Y images acquired on the Vision with 3 iterations, 5 subsets, and no post-reconstruction filter for quantitative imaging. The Vision provides a reduced noise level, but similar quantitative accuracy as compared with its predecessor the mCT.

Adaptive scan duration in SPECT: Evaluation for radioembolization.

PURPOSE: It may be challenging to select the optimal scan duration for single-photon emission computed tomography (SPECT) protocols because the activity distribution characteristics can differ in every scan. Using simulations and experiments, we investigated whether the scan duration can be optimized for every scan separately by evaluating the activity distribution during scanning. We refer to this as adaptive scanning. METHODS: The feasibility of adaptive scanning was evaluated for the detection of extrahepatic depositions in the pretreatment procedure of radioembolization, in which 99m Tc-labeled macroaggregated albumin (99m Tc-MAA) is injected into the liver. We simulated fast 1-min detector rotations and updated the reconstruction with the newly collected counts after every rotation. The scan was terminated when one of the two criteria was met: (a) when the mask difference of the detected extrahepatic deposition between two consecutive rotations was lower than 5%; or (b) when the reconstructed extrahepatic activity was negligible with respect to the total reconstructed activity (<0.075%). The performance of adaptive scanning was evaluated using a digital phantom with various activity distributions, a physical phantom experiment, and simulations based on 129 patient activity distributions. RESULTS: The digital phantom data showed that the scan termination times substantially depended on the activity distribution characteristics. The experimental phantom data showed the feasibility of adaptive scanning with physical scanner measurements and illustrated that fast detector motion was not limiting the adaptive scanning performance. The patient data showed a large spread in the scan terminations times. By adaptive scanning, the mean scan duration of the patient distributions was shortened from 20 min (current clinical protocol) to 4.8 ± 0.2 min. The detection accuracy of extrahepatic depositions was unaffected and the mean difference in the extrahepatic deposition masks (compared with the 20-min scan) was only 7.0 ± 1.0%. CONCLUSION: Our study suggests that the SPECT scan duration can be personalized by assessing the activity distribution characteristics during scanning for the detection of extrahepatic depositions in the pretreatment procedure of radioembolization. The adaptive scanning approach might also be of benefit for other SPECT protocols, as long as a measure of interest is available for optimization.

Feasibility of imaging 90 Y microspheres at diagnostic activity levels for hepatic radioembolization treatment planning.

PURPOSE: Prior to 90 Y hepatic radioembolization, a dosage of 99m Tc-macroaggregated albumin (99m Tc-MAA) is administered to simulate the distribution of the 90 Y-loaded microspheres. This pretreatment procedure enables lung shunt estimation, detection of potential extrahepatic depositions, and estimation of the intrahepatic dose distribution. However, the predictive accuracy of the MAA particle distribution is often limited. Ideally, 90 Y microspheres would also be used for the pretreatment procedure. Based on previous research, the pretreatment activity should be limited to the estimated safety threshold of 100 MBq, making imaging challenging. The purpose of this study was to evaluate the quality of intra- and extrahepatic imaging of 90 Y-based pretreatment positron emission tomography/computed tomography (PET/CT) and quantitative single photon emission computed tomography (SPECT)/CT scans, by means of phantom experiments and a patient study. METHODS: An anthropomorphic phantom with three extrahepatic depositions was filled with 90 Y chloride to simulate a lung shunt fraction (LSF) of 5.3% and a tumor to nontumor ratio (T/N) of 7.9. PET /CT (Siemens Biograph mCT) and Bremsstrahlung SPECT/CT (Siemens Symbia T16) images were acquired at activities ranging from 1999 MBq down to 24 MBq, representing post- and pretreatment activities. PET/CT images were reconstructed with the clinical protocol and SPECT/CT images were reconstructed with a quantitative Monte Carlo-based reconstruction protocol. Estimated LSF, T/N, contrast to noise ratio of all extrahepatic depositions, and liver parenchymal and tumor dose were compared with the phantom ground truth. A clinically reconstructed SPECT/CT of 150 MBq 99m Tc represented the current clinical standard. In addition, a 90 Y pretreatment scan was simulated for a patient by acquiring posttreatment PET/CT and SPECT/CT data with shortened acquisition times. RESULTS: At an activity of 100 MBq 90 Y, PET/CT overestimated LSF [+10 percentage point (pp)], underestimated liver parenchymal dose (-3 Gy/GBq), and could not detect the extrahepatic depositions. SPECT/CT more accurately estimated LSF (-0.7 pp), parenchymal dose (-0.3 Gy/GBq) and could detect all three extrahepatic depositions. 99m Tc SPECT/CT showed similar accuracy as 90 Y SPECT/CT (LSF: +0.2 pp, parenchymal dose: +0.4 Gy/GBq, all extrahepatic depositions visible), although the noise level in the liver compartment was considerably lower for 99m Tc SPECT/CT compared to 90 Y SPECT/CT. The patient's SPECT/CT simulating a pretreatment 90 Y procedure accurately represented the posttreatment 90 Y microsphere distribution. CONCLUSIONS: Quantitative SPECT/CT of 100 MBq 90 Y could accurately estimate LSF, T/N, parenchymal and tumor dose, and visualize extrahepatic depositions.

Designing phantoms to accurately replicate circular depolarization in biological scattering media.

We introduce an iterative method for designing optical phantoms that are able to replicate the depolarization profiles of various target media, including colloidal suspensions of Intralipid, bovine milk, and ex vivo samples of ovine kidney cortex tissue. The designed phantoms comprise spherical scattering particles with fine-tuned size distributions and are capable of simultaneously reproducing spatially resolved intensity measurements and depolarization measurements of target media when illuminated with circularly polarized light.

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.

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.

A Dual-layer Detector for Simultaneous Fluoroscopic and Nuclear Imaging.

Purpose To develop and evaluate a dual-layer detector capable of acquiring intrinsically registered real-time fluoroscopic and nuclear images in the interventional radiology suite. Materials and Methods The dual-layer detector consists of an x-ray flat panel detector placed in front of a γ camera with cone beam collimator focused at the x-ray focal spot. This design relies on the x-ray detector absorbing the majority of the x-rays while it is more transparent to the higher energy γ photons. A prototype was built and dynamic phantom images were acquired. In addition, spatial resolution and system sensitivity (evaluated as counts detected within the energy window per second per megabecquerel) were measured with the prototype. Monte Carlo simulations for an improved system with varying flat panel compositions were performed to assess potential spatial resolution and system sensitivity. Results Experiments with the dual-layer detector prototype showed that spatial resolution of the nuclear images was unaffected by the addition of the flat panel (full width at half maximum, 13.6 mm at 15 cm from the collimator surface). However, addition of the flat panel lowered system sensitivity by 45%-60% because of the nonoptimized transmission of the flat panel. Simulations showed that an attenuation of 27%-35% of the γ rays in the flat panel could be achieved by decreasing the crystal thickness and housing attenuation of the flat panel. Conclusion A dual-layer detector was capable of acquiring real-time intrinsically registered hybrid images, which could aid interventional procedures involving radionuclides. Published under a CC BY-NC-ND 4.0 license. Online supplemental material is available for this article.

The physics of radioembolization.

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.

Radioembolization lung shunt estimation based on a 90 Y pretreatment procedure: A phantom study.

PURPOSE: Prior to 90 Y radioembolization, a pretreatment 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 pretreatment 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 pretreatment scan, using an anthropomorphic phantom: (a) positron emission tomography/computed tomography (PET/CT), (b) Bremsstrahlung single photon emission tomography/computed tomography (SPECT/CT), and (c) 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 pretreatment procedure using a theoretically safe 90 Y activity as low as 70 MBq, when reconstructed with an MC-based model.

Technical Advances in Image Guidance of Radionuclide Therapy.

Internal radiation therapy with radionuclides (i.e., radionuclide therapy) owes its success to the many advantages over other, more conventional, treatment options. One distinct advantage of radionuclide therapies is the potential to use (part of) the emitted radiation for imaging of the radionuclide distribution. The combination of diagnostic and therapeutic properties in a set of matched radiopharmaceuticals (sometimes combined in a single radiopharmaceutical) is often referred to as theranostics and allows accurate diagnostic imaging before therapy. The use of imaging benefits treatment planning, dosimetry, and assessment of treatment response. This paper focuses on a selection of advances in imaging technology relevant for image guidance of radionuclide therapy. This involves developments in nuclear imaging modalities, as well as other anatomic and functional imaging modalities. The quality and quantitative accuracy of images used for guidance of radionuclide therapy is continuously being improved, which in turn may improve the therapeutic outcome and efficiency of radionuclide therapies.

Application of circularly polarized light for non-invasive diagnosis of cancerous tissues and turbid tissue-like scattering media.

Polarization-based optical techniques have become increasingly popular in the field of biomedical diagnosis. In the current report we exploit the directional awareness of circularly and/or elliptically polarized light backscattered from turbid tissue-like scattering media. We apply circularly and elliptically polarized laser light which illuminates the samples of interest, and a standard optical polarimeter is used to observe the polarization state of light backscattered a few millimeters away from the point of incidence. We demonstrate that the Stokes vector of backscattered light depicted on a Poincaré sphere can be used to assess a turbid tissue-like scattering medium. By tracking the Stokes vector of the detected light on the Poincaré sphere, we investigate the utility of this approach for characterization of cancerous and non-cancerous tissue samples in vitro. The obtained results are discussed in the framework of a phenomenological model and the results of a polarization tracking Monte Carlo model, developed in house. Schematic illustration of the experimental approach utilizing circularly and elliptically polarized light for probing turbid tissue-like scattering media.