Imaging techniques for guidance of radionuclide therapy

The aim of this thesis is to investigate imaging techniques for guidance of radionuclide therapy. The first part describes the development of instrumentation for guidance of radionuclide therapy. To date, no real-time hybrid imaging modalities for interventional purposes have been developed that combine simultaneously acquired nuclear and anatomic images. Real-time functional imaging in concert with anatomic imaging would provide the physician with valuable information during the procedure, thereby improving therapeutic efficiency. Procedures that can potentially benefit from real-time simultaneous hybrid imaging include liver radioembolization, biopsies. Measurements with our hybrid imaging prototype device have shown that simultaneous fluoroscopic and nuclear imaging of the same field of view is feasible. Accurate determination of the system parameters that describe the position of the x-ray tube, x-ray detector, gamma camera and collimators is crucial to optimize image quality. A calibration method was presented that improves the resolution and co-registration of simultaneously acquired hybrid fluoroscopic and nuclear images by estimating the geometric parameter set. The second part of this thesis concerns the quality of Single Photon Emission Computed Tomography (SPECT) images of high-energy photon-emitting isotopes. Methods to improve the quality of high-energy SPECT images are introduced, and the implications of reduced image quality in clinical practice are discussed. In SPECT using high-energy photon-emitting isotopes, such as 131I, parallel-hole collimators with thick septa are required to limit septal penetration, at the cost of sensitivity and resolution. To this end, we propose a collimator design (the parallel-cone (PC) collimator) consisting of a repetitive grid of parallel cones, capable of improving the image quality of high-energy SPECT. High-energy SPECT imaging with a single slice prototype of the proposed PC collimator has shown the potential for significantly improved image quality in comparison with standard parallel hole collimators. Radioiodine therapy with 131I is used for treatment of suspected recurrence of differentiated thyroid carcinoma. Pretherapeutic 124I Positron Emission Tomography/Computed Tomography (PET/CT) with a low activity (∼1% of 131I activity) can be performed to determine whether uptake of 131I, and thereby the desired therapeutic effect, may be expected. However, false-negative 124I PET/CT results as compared with posttherapeutic 131I SPECT/CT have been reported by several groups. Phantom measurements showed that the reported discrepancies may be ascribed to a difference in lesion detectability between 124I PET/CT and 131I SPECT/CT and, hence, higher 124I activities may be warranted to obtain equal detectability. Quantitative SPECT imaging of high-energy isotopes such as 131I remains a challenge, because of scatter and collimator penetration. The quality of SPECT images can be improved by incorporating scatter and collimator-detector-response (CDR) models in the reconstruction. By performing phantom measurements, it was shown that the reconstruction method incorporating Monte Carlo based scatter correction and simulated CDR modelling produced intrinsically quantitative 131I SPECT images with contrast recovery coefficient similar to the Triple Energy Window scatter correction method, without the use of experimentally determined weighting factors

Accuracy and precision of CPET equipment: a comparison of breath-by-breath and mixing chamber systems

Cardiopulmonary exercise testing (CPET) has become an important diagnostic tool for patients with cardiorespiratory disease and can monitor athletic performance measuring maximal oxygen uptake [Formula: see text]Vo2(; max). The aim of this study is to compare the accuracy and precision of a breath-by-breath and a mixing chamber CPET system, using two methods. First, this study developed a (theoretical) error analysis based on general error propagation theory. Second, calibration measurements using a metabolic simulator were performed. Error analysis shows that the error in oxygen uptake ([Formula: see text]Vo2) and carbon dioxide production (Vco2[Formula: see text]) is smaller for mixing chamber than for breath-by-breath systems. In general, the error of the flow sensor [Formula: see text]δV, the error in temperature of expired air δT(B) and the delay time error δt(delay) are significant sources of error. Measurements using a metabolic simulator show that breath-by-breath systems are less stabile for different values of minute ventilation than mixing chamber systems

Impact of reconstruction parameters on quantitative I-131 SPECT

Radioiodine therapy using I-131 is widely used for treatment of thyroid disease or neuroendocrine tumors. Monitoring treatment by accurate dosimetry requires quantitative imaging. The high energy photons however render quantitative SPECT reconstruction challenging, potentially requiring accurate correction for scatter and collimator effects. The goal of this work is to assess the effectiveness of various correction methods on these effects using phantom studies. A SPECT/CT acquisition of the NEMA IEC body phantom was performed. Images were reconstructed using the following parameters: (1) without scatter correction, (2) with triple energy window (TEW) scatter correction and (3) with Monte Carlo-based scatter correction. For modelling the collimator-detector response (CDR), both (a) geometric Gaussian CDRs as well as (b) Monte Carlo simulated CDRs were compared. Quantitative accuracy, contrast to noise ratios and recovery coefficients were calculated, as well as the background variability and the residual count error in the lung insert. The Monte Carlo scatter corrected reconstruction method was shown to be intrinsically quantitative, requiring no experimentally acquired calibration factor. It resulted in a more accurate quantification of the background compartment activity density compared with TEW or no scatter correction. The quantification error relative to a dose calibrator derived measurement was found to be  <1%,-26% and 33%, respectively. The adverse effects of partial volume were significantly smaller with the Monte Carlo simulated CDR correction compared with geometric Gaussian or no CDR modelling. Scatter correction showed a small effect on quantification of small volumes. When using a weighting factor, TEW correction was comparable to Monte Carlo reconstruction in all measured parameters, although this approach is clinically impractical since this factor may be patient dependent. Monte Carlo based scatter correction including accurately simulated CDR modelling is the most robust and reliable method to reconstruct accurate quantitative iodine-131 SPECT images

Impact of reconstruction parameters on quantitative I-131 SPECT

Radioiodine therapy using I-131 is widely used for treatment of thyroid disease or neuroendocrine tumors. Monitoring treatment by accurate dosimetry requires quantitative imaging. The high energy photons however render quantitative SPECT reconstruction challenging, potentially requiring accurate correction for scatter and collimator effects. The goal of this work is to assess the effectiveness of various correction methods on these effects using phantom studies. A SPECT/CT acquisition of the NEMA IEC body phantom was performed. Images were reconstructed using the following parameters: (1) without scatter correction, (2) with triple energy window (TEW) scatter correction and (3) with Monte Carlo-based scatter correction. For modelling the collimator-detector response (CDR), both (a) geometric Gaussian CDRs as well as (b) Monte Carlo simulated CDRs were compared. Quantitative accuracy, contrast to noise ratios and recovery coefficients were calculated, as well as the background variability and the residual count error in the lung insert. The Monte Carlo scatter corrected reconstruction method was shown to be intrinsically quantitative, requiring no experimentally acquired calibration factor. It resulted in a more accurate quantification of the background compartment activity density compared with TEW or no scatter correction. The quantification error relative to a dose calibrator derived measurement was found to be  <1%,-26% and 33%, respectively. The adverse effects of partial volume were significantly smaller with the Monte Carlo simulated CDR correction compared with geometric Gaussian or no CDR modelling. Scatter correction showed a small effect on quantification of small volumes. When using a weighting factor, TEW correction was comparable to Monte Carlo reconstruction in all measured parameters, although this approach is clinically impractical since this factor may be patient dependent. Monte Carlo based scatter correction including accurately simulated CDR modelling is the most robust and reliable method to reconstruct accurate quantitative iodine-131 SPECT images

Dual-head gamma camera system for intraoperative localization of radioactive seeds

Breast-conserving surgery is a standard option for the treatment of patients with early-stage breast cancer. This form of surgery may result in incomplete excision of the tumor. Iodine-125 labeled titanium seeds are currently used in clinical practice to reduce the number of incomplete excisions. It seems likely that the number of incomplete excisions can be reduced even further if intraoperative information about the location of the radioactive seed is combined with preoperative information about the extent of the tumor. This can be combined if the location of the radioactive seed is established in a world coordinate system that can be linked to the (preoperative) image coordinate system. With this in mind, we propose a radioactive seed localization system which is composed of two static ceiling-suspended gamma camera heads and two parallel-hole collimators. Physical experiments and computer simulations which mimic realistic clinical situations were performed to estimate the localization accuracy (defined as trueness and precision) of the proposed system with respect to collimator-source distance (ranging between 50 cm and 100 cm) and imaging time (ranging between 1 s and 10 s). The goal of the study was to determine whether or not a trueness of 5 mm can be achieved if a collimator-source distance of 50 cm and imaging time of 5 s are used (these specifications were defined by a group of dedicated breast cancer surgeons). The results from the experiments indicate that the location of the radioactive seed can be established with an accuracy of 1.6 mm ± 0.6 mm if a collimator-source distance of 50 cm and imaging time of 5 s are used (these experiments were performed with a 4.5 cm thick block phantom). Furthermore, the results from the simulations indicate that a trueness of 3.2 mm or less can be achieved if a collimator-source distance of 50 cm and imaging time of 5 s are used (this trueness was achieved for all 14 breast phantoms which were used in this study). Based on these results we conclude that the proposed system can be a valuable tool for (real-time) intraoperative breast cancer localization

The superior predictive value of 166Ho-scout compared with 99mTc-macroaggregated albumin prior to 166Ho-microspheres radioembolization in patients with liver metastases

Purpose: As an alternative to technetium-99m-macroaggregated albumin ( 99mTc-MAA), a scout dose of holmium-166 ( 166Ho) microspheres can be used prior to 166Ho-radioembolization. The use of identical particles for pre-treatment and treatment procedures may improve the predictive value of pre-treatment analysis of distribution. The aim of this study was to analyze the agreement between 166Ho-scout and 166Ho-therapeutic dose in comparison with the agreement between 99mTc-MAA and 166Ho-therapeutic dose. Methods: Two separate scout dose procedures were performed ( 99mTc-MAA and 166Ho-scout) before treatment in 53 patients. First, qualitative assessment was performed by two blinded nuclear medicine physicians who visually rated the agreement between the 99mTc-MAA, 166Ho-scout, and 166Ho-therapeutic dose SPECT-scans (i.e., all performed in the same patient) on a 5-point scale. Second, agreement was measured quantitatively by delineating lesions and normal liver on FDG-PET/CT. These volumes of interest (VOIs) were co-registered to the SPECT/CT images. The predicted absorbed doses (based on 99mTc-MAA and 166Ho-scout) were compared with the actual absorbed dose on post-treatment SPECT. Results: A total of 23 procedures (71 lesions, 22 patients) were included for analysis. In the qualitative analysis, 166Ho-scout was superior with a median score of 4 vs. 2.5 for 99mTc-MAA (p < 0.001). The quantitative analysis showed significantly narrower 95%-limits of agreement for 166Ho-scout in comparison with 99mTc-MAA when evaluating lesion absorbed dose (− 90.3 and 105.3 Gy vs. − 164.1 and 197.0 Gy, respectively). Evaluation of normal liver absorbed dose did not show difference in agreement between both scout doses and 166Ho-therapeutic dose (− 2.9 and 5.5 Gy vs − 3.6 and 4.1 Gy for 99mTc-MAA and 166Ho-scout, respectively). Conclusions: In this study, 166Ho-scout was shown to have a superior predictive value for intrahepatic distribution in comparison with 99mTc-MAA

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 superior predictive value of 166Ho-scout compared with 99mTc-macroaggregated albumin prior to 166Ho-microspheres radioembolization in patients with liver metastases

Purpose: As an alternative to technetium-99m-macroaggregated albumin ( 99mTc-MAA), a scout dose of holmium-166 ( 166Ho) microspheres can be used prior to 166Ho-radioembolization. The use of identical particles for pre-treatment and treatment procedures may improve the predictive value of pre-treatment analysis of distribution. The aim of this study was to analyze the agreement between 166Ho-scout and 166Ho-therapeutic dose in comparison with the agreement between 99mTc-MAA and 166Ho-therapeutic dose. Methods: Two separate scout dose procedures were performed ( 99mTc-MAA and 166Ho-scout) before treatment in 53 patients. First, qualitative assessment was performed by two blinded nuclear medicine physicians who visually rated the agreement between the 99mTc-MAA, 166Ho-scout, and 166Ho-therapeutic dose SPECT-scans (i.e., all performed in the same patient) on a 5-point scale. Second, agreement was measured quantitatively by delineating lesions and normal liver on FDG-PET/CT. These volumes of interest (VOIs) were co-registered to the SPECT/CT images. The predicted absorbed doses (based on 99mTc-MAA and 166Ho-scout) were compared with the actual absorbed dose on post-treatment SPECT. Results: A total of 23 procedures (71 lesions, 22 patients) were included for analysis. In the qualitative analysis, 166Ho-scout was superior with a median score of 4 vs. 2.5 for 99mTc-MAA (p < 0.001). The quantitative analysis showed significantly narrower 95%-limits of agreement for 166Ho-scout in comparison with 99mTc-MAA when evaluating lesion absorbed dose (− 90.3 and 105.3 Gy vs. − 164.1 and 197.0 Gy, respectively). Evaluation of normal liver absorbed dose did not show difference in agreement between both scout doses and 166Ho-therapeutic dose (− 2.9 and 5.5 Gy vs − 3.6 and 4.1 Gy for 99mTc-MAA and 166Ho-scout, respectively). Conclusions: In this study, 166Ho-scout was shown to have a superior predictive value for intrahepatic distribution in comparison with 99mTc-MAA