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Spatially resolved assessment of hepatic function using 99mTc-IDA SPECT

Purpose: 99mTc-iminodiacetic acid (IDA) hepatobiliary imaging is usually quantified for hepatic function on the entire liver or regions of interest (ROIs) in the liver. The authors presented a method to estimate the hepatic extraction fraction (HEF) voxel-by-voxel from single-photon emission computed tomography (SPECT)/CT with a 99mTc-labeled IDA agent of mebrofenin and evaluated the spatially resolved HEF measurements with an independent physiological measurement.Methods: Fourteen patients with intrahepatic cancers were treated with radiation therapy (RT) and imaged by 99mTc-mebrofenin SPECT before and 1 month after RT. The dynamic SPECT volumes were with a resolution of 3.9 × 3.9 × 2.5 mm{sup 3}. Throughout the whole liver with approximate 50 000 voxels, voxelwise HEF quantifications were estimated and compared between using arterial input function (AIF) from the heart and using vascular input function (VIF) from the spleen. The correlation between mean of the HEFs over the nontumor liver tissue and the overall liver function measured by Indocyanine green clearance half-time (T1/2) was assessed. Variation of the voxelwise estimation was evaluated in ROIs drawn in relatively homogeneous regions of the livers. The authors also examined effects of the time range parameter on the voxelwise HEF quantification.Results: Mean of the HEFs over the liver estimated using AIF significantly correlated with the physiological measurement T1/2 (r= 0.52, p= 0.0004), and the correlation was greatly improved by using VIF (r= 0.79, p < 0.0001). The parameter of time range for the retention phase did not lead to a significant difference in the means of the HEFs in the ROIs. Using VIF and a retention phase time range of 7–30 min, the relative variation of the voxelwise HEF in the ROIs was 10%± 6% of respective mean HEF.Conclusions: The voxelwise HEF derived from 99mTc-IDA SPECT by the deconvolution analysis is feasible to assess the spatial distribution of hepatic function in the liver.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Implications of CT noise and artifacts for quantitative {sup 99m}Tc SPECT/CT imaging

Purpose: This paper evaluates the effects of computed tomography (CT) image noise and artifacts on quantitative single-photon emission computed-tomography (SPECT) imaging, with the aim of establishing an appropriate range of CT acquisition parameters for low-dose protocols with respect to accurate SPECT attenuation correction (AC). Methods: SPECT images of two geometric and one anthropomorphic phantom were reconstructed iteratively using CT scans acquired at a range of dose levels (CTDI{sub vol} = 0.4 to 46 mGy). Resultant SPECT image quality was evaluated by comparing mean signal, background noise, and artifacts to SPECT images reconstructed using the highest dose CT for AC. Noise injection was performed on linear-attenuation (μ) maps to determine the CT noise threshold for accurate AC. Results: High levels of CT noise (σ ∼ 200–400 HU) resulted in low μ-maps noise (σ ∼ 1%–3%). Noise levels greater than ∼10% in 140 keV μ-maps were required to produce visibly perceptible increases of ∼15% in {sup 99m}Tc SPECT images. These noise levels would be achieved at low CT dose levels (CTDI{sub vol} = 4 μGy) that are over 2 orders of magnitude lower than the minimum dose for diagnostic CT scanners. CT noise could also lower (bias) the expected μ values. The relative error in reconstructed SPECT signal trended linearly with the relative shift in μ. SPECT signal was, on average, underestimated in regions corresponding with beam-hardening artifacts in CT images. Any process that has the potential to change the CT number of a region by ∼100 HU (e.g., misregistration between CT images and SPECT images due to motion, the presence of contrast in CT images) could introduce errors in μ{sub 140} {sub keV} on the order of 10%, that in turn, could introduce errors on the order of ∼10% into the reconstructed {sup 99m}Tc SPECT image. Conclusions: The impact of CT noise on SPECT noise was demonstrated to be negligible for clinically achievable CT parameters. Because CT dose levels that affect SPECT quantification is low (CTDI{sub vol} ∼ 4 μGy), the low dose limit for the CT exam as part of SPECT/CT will be guided by CT image quality requirements for anatomical localization and artifact reduction. A CT technique with higher kVp in combination with lower mAs is recommended when low-dose CT images are used for AC to minimize beam-hardening artifacts.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

On the dose calculation at the cellular level and its implications for the RBE of {sup 99m}Tc and {sup 123}I

Purpose: Based on the authors’ previous findings concerning the radiotoxicity of{sup 99m}Tc, the authors compared the cellular survival under the influence of this nuclide with that following exposure to the Auger electron emitter {sup 123}I. To evaluate the relative biological effectiveness (RBE) of both radionuclides, knowledge of the absorbed dose is essential. Thus, the authors present the dose calculations and discuss the results based on different models of the radionuclide distribution. Both different target volumes and the influence of the uptake kinetics were considered. Methods: Rat thyroid PC Cl3 cells in culture were incubated with either{sup 99m}Tc or {sup 123}I or were irradiated using 200 kV x-rays in the presence or absence of perchlorate. The clonogenic cell survival was measured via colony formation. In addition, the intracellular radionuclide uptake was quantified. Single-cell dose calculations were based on Monte Carlo simulations performed using Geant4. Results: Compared with external radiation using x-rays (D{sub 37} = 2.6 Gy), the radionuclides {sup 99m}Tc (D{sub 37} = 3.5 Gy), and {sup 123}I (D{sub 37} = 3.8 Gy) were less toxic in the presence of perchlorate. In the absence of perchlorate, the amount of activity a{sub 37} that was necessary to reduce the surviving fraction (SF) to 0.37 was 22.8 times lower for {sup 99m}Tc and 12.4 times lower for {sup 123}I because of the dose increase caused by intracellular radionuclide accumulation. When the cell nucleus was considered as the target for the dose calculation, the authors found a RBE of 2.18 for {sup 99m}Tc and RBE = 3.43 for {sup 123}I. Meanwhile, regarding the dose to the entire cell, RBE = 0.75 for {sup 99m}Tc and RBE = 1.87 for {sup 123}I. The dose to the entire cell was chosen as the dose criterion because of the intracellular radionuclide accumulation, which was found to occur solely in the cytoplasm. The calculated number of intracellular decays per cell was (975 ± 109) decays/MBq for {sup 99m}Tc and (221 ± 82) decays/MBq for {sup 123}I. Conclusions: The authors’ data indicate that extra-nuclear targets to Auger electrons exist, which is obvious from our dose calculations. When considering the dose to the cell nucleus, the authors found an enhanced RBE for{sup 99m}Tc and {sup 123}I relative to acute x-ray irradiation and pure extracellular irradiation with both radionuclides. Surprisingly, the authors did not find any radionuclide accumulation in the cell nucleus, indicating that there are additional radiosensitive targets besides the DNA. In addition, the authors demonstrated the necessity of cellular dose calculations in radiobiological experiments using unsealed radionuclides and identified the relevant parameters.

60 APPLIED LIFE SCIENCES↗

Innovative methodology for intercomparison of radionuclide calibrators using short half-life in situ prepared radioactive sources

Purpose: An original radionuclide calibrator method for activity determination is presented. The method could be used for intercomparison surveys for short half-life radioactive sources used in Nuclear Medicine, such as{sup 99m}Tc or most positron emission tomography radiopharmaceuticals. Methods: By evaluation of the resulting net optical density (netOD) using a standardized scanning method of irradiated Gafchromic XRQA2 film, a comparison of the netOD measurement with a previously determined calibration curve can be made and the difference between the tested radionuclide calibrator and a radionuclide calibrator used as reference device can be calculated. To estimate the total expected measurement uncertainties, a careful analysis of the methodology, for the case of{sup 99m}Tc, was performed: reproducibility determination, scanning conditions, and possible fadeout effects. Since every factor of the activity measurement procedure can influence the final result, the method also evaluates correct syringe positioning inside the radionuclide calibrator. Results: As an alternative to using a calibrated source sent to the surveyed site, which requires a relatively long half-life of the nuclide, or sending a portable calibrated radionuclide calibrator, the proposed method uses a source preparedin situ. An indirect activity determination is achieved by the irradiation of a radiochromic film using {sup 99m}Tc under strictly controlled conditions, and cumulated activity calculation from the initial activity and total irradiation time. The irradiated Gafchromic film and the irradiator, without the source, can then be sent to a National Metrology Institute for evaluation of the results. Conclusions: The methodology described in this paper showed to have a good potential for accurate (3%) radionuclide calibrators intercomparison studies for{sup 99m}Tc between Nuclear Medicine centers without source transfer and can easily be adapted to other short half-life radionuclides.

07 ISOTOPE AND RADIATION SOURCES↗

SU-C-9A-04: Alternative Analytic Solution to the Paralyzable Detector Model to Calculate Deadtime and Deadtime Loss

Purpose: Some common methods to solve for deadtime are (1) dual-source method, which assumes two equal activities; (2) model fitting, which requires multiple acquisitions as source decays; and (3) lossless model, which assumes no deadtime loss at low count rates. We propose a new analytic alternative solution to calculate deadtime for paralyzable gamma camera. Methods: Deadtime T can be calculated analytically from two distinct observed count rates M1 and M2 when the ratio of the true count rates alpha=N2/N1 is known. Alpha can be measured as a ratio of two measured activities using dose calibrators or via radioactive decay. Knowledge of alpha creates a system with 2 equations and 2 unknowns, i.e., T and N1. To verify the validity of the proposed method, projections of a non-uniform phantom (4GBq 99mTc) were acquired in using Siemens SymbiaS multiple times over 48 hours. Each projection has >100kcts. The deadtime for each projection was calculated by fitting the data to a paralyzable model and also by using the proposed 2-acquisition method. The two estimates of deadtime were compared using the Bland-Altmann method. In addition, the dependency of uncertainty in T on uncertainty in alpha was investigated for several imaging conditions. Results: The results strongly suggest that the 2-acquisition method is equivalent to the fitting method. The Bland-Altman analysis yielded mean difference in deadtime estimate of ∼0.076us (95%CI: -0.049us, 0.103us) between the 2-acquisition and model fitting methods. The 95% limits of agreement were calculated to be -0.104 to 0.256us. The uncertainty in deadtime calculated using the proposed method is highly dependent on the uncertainty in the ratio alpha. Conclusion: The 2-acquisition method was found to be equivalent to the parameter fitting method. The proposed method offers a simpler and more practical way to analytically solve for a paralyzable detector deadtime, especially during physics testing.

07 ISOTOPE AND RADIATION SOURCES↗

SU-C-9A-05: A Medical Physics Approach to the Evaluation of a New Anti-Reflux Catheter

Purpose: The Surefire Infusion System (SIS) is a coaxial microcatheter system with a pliant expanding tip designed to limit retrograde flow of administered intra-arterial embolic agents and resultant non-target embolization (NTE). A recent study suggests that the SIS may achieve relative arterial hypotension downstream to the catheter tip when compared to an end-hole catheter, potentially altering microsphere distribution. We have used a physics based approach to evaluate particulate distribution using both the SIS and standard end-hole microcatheter via a two-step same-day injection of Tc-99m MAA as a microsphere surrogate. Methods: Informed patient consent and IRB approval were obtained. Four patients with primary or secondary liver cancer underwent two sequential low-particulate infusions of Tc-99m MAA on the same day using both the SIS and a conventional end-hole catheter. Radiopharmaceutical dosages of approximately 1:8 were utilized in the first infusion relative to the second to eliminate the effect of residual activity on the images acquired after each step. SPECT imaging was obtained following each infusion, and MAA distribution was analyzed and compared. Archived fluoroscopic images confirmed near-identical catheter position for both infusions. Results: SPECT images from all four patients demonstrate qualitatively increased penetration of MAA distal to the site of infusion using the SIS when compared to a standard end-hole catheter. Quantitative evaluations corroborate these findings with some distal regions receiving between 33% to more than 200% greater relative activity when SIS was used. No appreciable NTE was identified in either patient subset. Conclusion: These preliminary data demonstrate the validity of this dual-infusion technique. Both qualitative and quantitative assessment of SPECT images and comparison with baseline contrast enhanced CT and PET/CT images indicate an improvement in MAA penetration into the target lesion with the SIS. However, the degree of improvement is highly dependent on tumor type and size. Financial support provided by Surefire Medical.

60 APPLIED LIFE SCIENCES↗

SU-C-9A-07: Fabrication and Calibration of a Novel High-Sensitivity Collimator for Brain SPECT Imaging

Purpose: We have designed a novel collimator for brain SPECT imaging that yields greatly increased sensitivity near the center of the brain without loss of resolution. The collimator was manufactured and initial evaluation has been completed. Methods: The collimator was time-consuming and challenging to build. Because our desired hole pattern required substantial variations in hole angle, we designed two supporting plates to securely position about 34,000 hexagonal, slightly tapered, 75-mm long steel pins. The holes in the plates were modeled to yield the desired focal length, hole length and septal thickness. Molten lead was poured in between the plates, and all pins were removed after cooling. The sensitivity gain compared to a fan-beam collimator was measured using a point source placed along the central ray at several distances from the collimator face. Visual inspection of the holes was not possible as the collimator was sealed so it could be safely mounted on a SPECT system. Therefore, we prepared a 2D array of 768, ∼48μCi Tc-99m point sources, separated by 1.6 cm. The array was imaged for 10 minutes at 4 shifted locations to reduce sampling distance to 8 mm. Results: The sensitivity of the novel cone-beam collimator varied with distance from the detector face; it was higher than that of the fan-beam collimator by factors ranging from 3 to 176. Examination of the projections of the 4×768 point sources revealed that fewer than 2% of the holes were fully or partially blocked, which indicates that the intensive manual fabrication process was very successful. Conclusion: We have designed and manufactured a novel collimator for brain SPECT imaging. As expected, the sensitivity is much higher than that of a fan-beam collimator. Because of differences between the manufactured collimator and its design, reconstruction of the data will require a measured system function.

60 APPLIED LIFE SCIENCES↗

SU-E-T-116: Dose Response in the Treatment of Unresectable Cholangiocarcinoma with Yttrium-90 Microspheres

Purpose: The purpose of this study is to assess the dose response of radioembolization using yttrium-90 (Y-90) microspheres in patients treated for unresectable cholangiocarcinoma. This study utilized partition dosimetry model for the dose calculation. The results show survival benefit with dose escalation. Methods: Between February 2009 and March 2013, ten patients with pathology proven unresectable cholangiocarcinoma were radioembolized with Y-90 microspheres. Patients underwent initial pre-treatment angiographic assessment for blood flow and 99mTc- MAA for lung shunt evaluation. Activity of Y-90 administration was calculated using the Body Surface Area (BSA) and target volumes which were determined by contouring the pre-treatment MRI/CT images using a radiation therapy treatment planning system. Medical Internal Radiation Dose (MIRD) method was used to assess the dosimetric results of Y90. Partition model based on the tumor to-liver activity uptake estimated from pretreatment 99mTc- MAA study was used to calculate the dose delivered to the target. The variables assessed included: administered dose, toxicity based on clinical changes, imaging based tumor response, and survival. Results: Ten patients were radioembolized with Y-90 microspheres to either one hepatic lobe or both left and right lobes. Patients were stratified by dose. Four patients who received dose greater than 140Gy (p < 0.05) all survived. The corresponding activity they received was greater than 35 mCi. Six out of ten patients died of disease with median survival of 18 weeks (range 12–81wks). Conclusion: Given the growing body of data for Y-90 microspheres in the context of cholangiocarcinoma, radioembolization may become an important treatment modality for an appropriately selected group of patients. Our study further substantiates past studies and shows additional evidence of a survival benefit with dose escalation.

60 APPLIED LIFE SCIENCES↗

SU-E-T-402: Y-90 Microspheres (SIR Spheres) for Treatment of Liver Metastasis : Technique

Purpose: The purpose of this presentation is to discuss the radiation safety and dosimetric technique used for the therapeutic procedure using Y-90 microspheres through intra -arterial administration on patients with liver metastasis Methods: The radiation dosimetry, technique and safety aspects of 14 patients with primary and metastatic liver cancer, treated with Y-90 microsphere (SIR spheres) are discussed. The liver and tumor volumes were determined using the CT and MR scans . The images were imported into the treatment planning system and the liver and tumor volumes and the volume of the liver affected were outlined and the volume calculation was performed using the software. The lung shunt fraction (LSF) and tumor to liver uptake ratio (TLR) were determined using the nuclear medicine SPECT imaging with Tc-99m MAA. The absorbed dose to the target volume in liver was calculated using the following equation:Dose ? (Gy) = C x E? x 5.92 x 10-6 (Gy/s) x T(1/2)(days) x 1.44 x 8.64 x 104 (s) The distribution of activity in the tumor bed was confirmed by post Y-90 administration imaging using the Bremsstrahlung peak at 30% window. The patient and the procedure room were surveyed and radiation safety instructions were given to the patient Results: The tumor volume ranged from 77 cc to 700 cc, tumor to liver uptake ranged from 3 to 12. The lung shunt fraction varied from 1.08% to 9.0%. The activity administered ranged from 1.0GBq to 2.5 GBq, . The radiation survey in contact with the patient ranged from 1.8 mR/hr to 2.5 mR/hr and reading at 1 meter was less than 0.2 mR/hr Conclusion: The technique for radiation dosimetry and radiation safety for Y-90 microsphere therapy is established. The post treatment imaging helped to confirm the distribution of Y-90 microspheres inside the tumor bed.

60 APPLIED LIFE SCIENCES↗

SU-E-CAMPUS-I-05: Internal Dosimetric Calculations for Several Imaging Radiopharmaceuticals in Preclinical Studies and Quantitative Assessment of the Mouse Size Impact On Them. Realistic Monte Carlo Simulations Based On the 4D-MOBY Model

Purpose: Commonly used radiopharmaceuticals were tested to define the most important dosimetric factors in preclinical studies. Dosimetric calculations were applied in two different whole-body mouse models, with varying organ size, so as to determine their impact on absorbed doses and S-values. Organ mass influence was evaluated with computational models and Monte Carlo(MC) simulations. Methods: MC simulations were executed on GATE to determine dose distribution in the 4D digital MOBY mouse phantom. Two mouse models, 28 and 34 g respectively, were constructed based on realistic preclinical exams to calculate the absorbed doses and S-values of five commonly used radionuclides in SPECT/PET studies (18F, 68Ga, 177Lu, 111In and 99mTc).Radionuclide biodistributions were obtained from literature. Realistic statistics (uncertainty lower than 4.5%) were acquired using the standard physical model in Geant4. Comparisons of the dosimetric calculations on the two different phantoms for each radiopharmaceutical are presented. Results: Dose per organ in mGy was calculated for all radiopharmaceuticals. The two models introduced a difference of 0.69% in their brain masses, while the largest differences were observed in the marrow 18.98% and in the thyroid 18.65% masses.Furthermore, S-values of the most important target-organs were calculated for each isotope. Source-organ was selected to be the whole mouse body.Differences on the S-factors were observed in the 6.0–30.0% range. Tables with all the calculations as reference dosimetric data were developed. Conclusion: Accurate dose per organ and the most appropriate S-values are derived for specific preclinical studies. The impact of the mouse model size is rather high (up to 30% for a 17.65% difference in the total mass), and thus accurate definition of the organ mass is a crucial parameter for self-absorbed S values calculation.Our goal is to extent the study for accurate estimations in small animal imaging, whereas it is known that there is a large variety in the anatomy of the organs.

60 APPLIED LIFE SCIENCES↗

MO-G-17A-04: Internal Dosimetric Calculations for Pediatric Nuclear Imaging Applications, Using Monte Carlo Simulations and High-Resolution Pediatric Computational Models

Purpose: Our purpose is to evaluate the administered absorbed dose in pediatric, nuclear imaging studies. Monte Carlo simulations with the incorporation of pediatric computational models can serve as reference for the accurate determination of absorbed dose. The procedure of the calculated dosimetric factors is described, while a dataset of reference doses is created. Methods: Realistic simulations were executed using the GATE toolkit and a series of pediatric computational models, developed by the “IT'IS Foundation”. The series of the phantoms used in our work includes 6 models in the range of 5–14 years old (3 boys and 3 girls). Pre-processing techniques were applied to the images, to incorporate the phantoms in GATE simulations. The resolution of the phantoms was set to 2 mm3. The most important organ densities were simulated according to the GATE “Materials Database”. Several used radiopharmaceuticals in SPECT and PET applications are being tested, following the EANM pediatric dosage protocol. The biodistributions of the several isotopes used as activity maps in the simulations, were derived by the literature. Results: Initial results of absorbed dose per organ (mGy) are presented in a 5 years old girl from the whole body exposure to 99mTc - SestaMIBI, 30 minutes after administration. Heart, kidney, liver, ovary, pancreas and brain are the most critical organs, in which the S-factors are calculated. The statistical uncertainty in the simulation procedure was kept lower than 5%. The Sfactors for each target organ are calculated in Gy/(MBq*sec) with highest dose being absorbed in kidneys and pancreas (9.29*10{sup 10} and 0.15*10{sup 10} respectively). Conclusion: An approach for the accurate dosimetry on pediatric models is presented, creating a reference dosage dataset for several radionuclides in children computational models with the advantages of MC techniques. Our study is ongoing, extending our investigation to other reference models and evaluating the results with clinical estimated doses.

60 APPLIED LIFE SCIENCES↗

TU-F-12A-04: Differential Radiation Avoidance of Functional Liver Regions Defined by 99mTc-Sulfur Colloid SPECT/CT with Proton Therapy

Purpose: Radiotherapy for hepatocellular carcinoma patients is conventionally planned without consideration of spatial heterogeneity in hepatic function, which may increase risk of radiation-induced liver disease. Pencil beam scanning (PBS) proton radiotherapy (pRT) plans were generated to differentially decrease dose to functional liver volumes (FLV) defined on [{sup 99m}Tc]sulfur colloid (SC) SPECT/CT images (functional avoidance plans) and compared against conventional pRT plans. Methods: Three HCC patients underwent SC SPECT/CT scans for pRT planning acquired 15 min post injection over 24 min. Images were reconstructed with OSEM following scatter, collimator, and exhale CT attenuation correction. Functional liver volumes (FLV) were defined by liver:spleen uptake ratio thresholds (43% to 90% maximum). Planning objectives to FLV were based on mean SC SPECT uptake ratio relative to GTV-subtracted liver and inversely scaled to mean liver dose of 20 Gy. PTV target coverage (V{sub 95}) was matched between conventional and functional avoidance plans. PBS pRT plans were optimized in RayStation for single field uniform dose (SFUD) and systematically perturbed to verify robustness to uncertainty in range, setup, and motion. Relative differences in FLV DVH and target dose heterogeneity (D{sub 2}-D{sub 98})/D50 were assessed. Results: For similar liver dose between functional avoidance and conventional PBS pRT plans (D{sub mean}≤5% difference, V{sub 18Gy}≤1% difference), dose to functional liver volumes were lower in avoidance plans but varied in magnitude across patients (FLV{sub 70%max} D{sub mean}≤26% difference, V{sub 18Gy}≤8% difference). Higher PTV dose heterogeneity in avoidance plans was associated with lower functional liver dose, particularly for the largest lesion [(D{sub 2}-D{sub 98})/D{sub 50}=13%, FLV{sub 90%max}=50% difference]. Conclusion: Differential avoidance of functional liver regions defined on sulfur colloid SPECT/CT is feasible with proton therapy. The magnitude of benefit appears to be patient specific and dependent on tumor location, size, and proximity to functional volumes. Further investigation in a larger cohort of patients may validate the clinical utility of functional avoidance planning of HCC radiotherapy.

60 APPLIED LIFE SCIENCES↗

TH-C-17A-02: New Radioluminescence Strategies Based On CRET (Cerenkov Radiation Energy Transfer) for Imaging and Therapy

Purpose: Cerenkov photons are produced when charged particles, emitted from radionuclides, travel through a media with a speed greater than that of the light in the media. Cerenkov radiation is mostly in the UV/Blue region and, thus, readily absorbed by biological tissue. Cerenkov Radiation Energy Transfer (CRET) is a wavelength-shifting phenomenon from blue Cerenkov light to more penetrating red wavelengths. We demonstrate the feasibility of in-depth imaging of CRET light originating from radionuclides realized by down conversion of gold nanoclusters (AuNCs, a novel particle composed of few atoms of gold coated with serum proteins) in vivo. Methods: Bovine Serum Albumin, Human Serum Albumin and Transferrin conjugated gold nanoclusters were synthesized, characterized and examined for CRET. Three different clinically used radiotracers: 18F-FDG, 90Y and 99mTc were used. Optical spectrum (440–750 nm) was recorded by sensitive bioluminescence imaging system at physiological temperature. Dose dependence (activity range from 0.5 up to 800uCi) and concentration dependence (0.01 to 1uM) studies were carried out. The compound was also imaged in a xenograft mouse model. Results: Only β+ and β--emitting radionuclides (18F-FDG, 90Y) are capable of CRET; no signal was found in 99mTc (γ-emitter). The emission peak of CRET by AuNCs was found to be ∼700 nm and was ∼3 fold times of background. In vitro studies showed a linear dependency between luminescence intensity and dose and concentration. CRET by gold nanoclusters was observed in xenografted mice injected with 100uCi of 18F-FDG. Conclusion: The unique optical, transport and chemical properties of AuNCs (gold nanoclusters) make them ideal candidates for in-vivo imaging applications. Development of new molecular imaging probes will allow us to achieve substantially improved spatiotemporal resolution, sensitivity and specificity for tumor imaging and detection.

60 APPLIED LIFE SCIENCES↗

TH-C-17A-06: A Hardware Implementation and Evaluation of Robotic SPECT: Toward Molecular Imaging Onboard Radiation Therapy Machines

Purpose: To construct a robotic SPECT system and demonstrate its capability to image a thorax phantom on a radiation therapy flat-top couch. The system has potential for on-board functional and molecular imaging in radiation therapy. Methods: A robotic SPECT imaging system was developed utilizing a Digirad 2020tc detector and a KUKA KR150-L110 robot. An imaging study was performed with the PET CT Phantom, which includes 5 spheres: 10, 13, 17, 22 and 28 mm in diameter. Sphere-tobackground concentration ratio was 6:1 of Tc99m. The phantom was placed on a flat-top couch. SPECT projections were acquired with a parallel-hole collimator and a single pinhole collimator. The robotic system navigated the detector tracing the flat-top table to maintain the closest possible proximity to the phantom. For image reconstruction, detector trajectories were described by six parameters: radius-of-rotation, x and z detector shifts, and detector rotation θ, tilt ϕ and twist γ. These six parameters were obtained from the robotic system by calibrating the robot base and tool coordinates. Results: The robotic SPECT system was able to maneuver parallel-hole and pinhole collimated SPECT detectors in close proximity to the phantom, minimizing impact of the flat-top couch on detector-to-COR (center-ofrotation) distance. In acquisitions with background at 1/6th sphere activity concentration, photopeak contamination was heavy, yet the 17, 22, and 28 mm diameter spheres were readily observed with the parallel hole imaging, and the single, targeted sphere (28 mm diameter) was readily observed in the pinhole region-of-interest (ROI) imaging. Conclusion: Onboard SPECT could be achieved by a robot maneuvering a SPECT detector about patients in position for radiation therapy on a flat-top couch. The robot inherent coordinate frame could be an effective means to estimate detector pose for use in SPECT image reconstruction. PHS/NIH/NCI grant R21-CA156390-01A1.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Comparison of internal dose estimates obtained using organ-level, voxel S value, and Monte Carlo techniques

Purpose: The authors’ objective was to compare internal dose estimates obtained using the Organ Level Dose Assessment with Exponential Modeling (OLINDA/EXM) software, the voxel S value technique, and Monte Carlo simulation. Monte Carlo dose estimates were used as the reference standard to assess the impact of patient-specific anatomy on the final dose estimate. Methods: Six patients injected with{sup 99m}Tc-hydrazinonicotinamide-Tyr{sup 3}-octreotide were included in this study. A hybrid planar/SPECT imaging protocol was used to estimate {sup 99m}Tc time-integrated activity coefficients (TIACs) for kidneys, liver, spleen, and tumors. Additionally, TIACs were predicted for {sup 131}I, {sup 177}Lu, and {sup 90}Y assuming the same biological half-lives as the {sup 99m}Tc labeled tracer. The TIACs were used as input for OLINDA/EXM for organ-level dose calculation and voxel level dosimetry was performed using the voxel S value method and Monte Carlo simulation. Dose estimates for {sup 99m}Tc, {sup 131}I, {sup 177}Lu, and {sup 90}Y distributions were evaluated by comparing (i) organ-level S values corresponding to each method, (ii) total tumor and organ doses, (iii) differences in right and left kidney doses, and (iv) voxelized dose distributions calculated by Monte Carlo and the voxel S value technique. Results: The S values for all investigated radionuclides used by OLINDA/EXM and the corresponding patient-specific S values calculated by Monte Carlo agreed within 2.3% on average for self-irradiation, and differed by as much as 105% for cross-organ irradiation. Total organ doses calculated by OLINDA/EXM and the voxel S value technique agreed with Monte Carlo results within approximately ±7%. Differences between right and left kidney doses determined by Monte Carlo were as high as 73%. Comparison of the Monte Carlo and voxel S value dose distributions showed that each method produced similar dose volume histograms with a minimum dose covering 90% of the volume (D90) agreeing within ±3%, on average. Conclusions: Several aspects of OLINDA/EXM dose calculation were compared with patient-specific dose estimates obtained using Monte Carlo. Differences in patient anatomy led to large differences in cross-organ doses. However, total organ doses were still in good agreement since most of the deposited dose is due to self-irradiation. Comparison of voxelized doses calculated by Monte Carlo and the voxel S value technique showed that the 3D dose distributions produced by the respective methods are nearly identical.

60 APPLIED LIFE SCIENCES↗

Sci—Thur PM: Imaging — 01: Position-sensitive noise characteristics in multi-pinhole cardiac SPECT imaging

Myocardial perfusion imaging (MPI) with Single Photon Emission Computed Tomography (SPECT) is invaluable in the diagnosis and management of heart disease. It provides essential information on myocardial blood flow and ischemia. Multi-pinhole dedicated cardiac-SPECT cameras offer improved count sensitivity, and spatial and energy resolutions over parallel-hole camera designs however variable sensitivity across the field-of-view (FOV) can lead to position-dependent noise variations. Since MPI evaluates differences in the signal-to-noise ratio, noise variations in the camera could significantly impact the sensitivity of the test for ischemia. We evaluated the noise characteristics of GE Healthcare's Discovery NM530c camera with a goal of optimizing the accuracy of our patient assessment and thereby improving outcomes. Theoretical sensitivity maps of the camera FOV, including attenuation effects, were estimated analytically based on the distance and angle between the spatial position of a given voxel and each pinhole. The standard deviation in counts, σ was inferred for each voxel position from the square root of the sensitivity mapped at that position. Noise was measured experimentally from repeated (N=16) acquisitions of a uniform spherical Tc-99m-water phantom. The mean (μ) and standard deviation (σ) were calculated for each voxel position in the reconstructed FOV. Noise increased ∼2.1× across a 12 cm sphere. A correlation of 0.53 is seen when experimental noise is compared with theory suggesting that ∼53% of the noise is attributed to the combined effects of attenuation and the multi-pinhole geometry. Further investigations are warranted to determine the clinical impact of the position-dependent noise variation.

60 APPLIED LIFE SCIENCES↗

Sci—Thur PM: Imaging — 04: An iterative triple energy window (TEW) approach to cross talk correction in quantitative small animal Tc99m and In111 SPECT

Dual isotope SPECT allows simultaneous measurement of two different tracers in vivo. With In111 (emission energies of 171keV and 245keV) and Tc99m (140keV), quantification of Tc99m is degraded by cross talk from the In111 photons that scatter and are detected at an energy corresponding to Tc99m. TEW uses counts recorded in two narrow windows surrounding the Tc99m primary window to estimate scatter. Iterative TEW corrects for the bias introduced into the TEW estimate resulting from un-scattered counts detected in the scatter windows. The contamination in the scatter windows is iteratively estimated and subtracted as a fraction of the scatter-corrected primary window counts. The iterative TEW approach was validated with a small-animal SPECT/CT camera using a 2.5mL plastic container holding thoroughly mixed Tc99m/In111 activity fractions of 0.15, 0.28, 0.52, 0.99, 2.47 and 6.90. Dose calibrator measurements were the gold standard. Uncorrected for scatter, the Tc99m activity was over-estimated by as much as 80%. Unmodified TEW underestimated the Tc99m activity by 13%. With iterative TEW corrections applied in projection space, the Tc99m activity was estimated within 5% of truth across all activity fractions above 0.15. This is an improvement over the non-iterative TEW, which could not sufficiently correct for scatter in the 0.15 and 0.28 phantoms.

60 APPLIED LIFE SCIENCES↗

Sci—Thur PM: Imaging — 05: Calibration of a SPECT/CT camera for quantitative SPECT with {sup 99m}Tc

While quantitation is the norm in PET, it is not widely available yet in SPECT. This work's aim was to calibrate a commercially available SPECT/CT system to perform quantitative SPECT. Counting sensitivity, dead-time (DT) constant and partial volume effect (PVE) of the system were assessed. A dual-head Siemens SymbiaT6 SPECT/CT camera equipped with low energy high-resolution collimators was studied. {sup 99m}Tc was the radioisotope of interest because of its wide usage in nuclear medicine. First, point source acquisitions were performed (activity: 30–990MBq). Further acquisitions were then performed with a uniform Jaszczak phantom filled with water at high activity (25–5000MBq). PVE was studied using 6 hot spheres (diameters: 9.9–31.2 mm) filled with {sup 99m}Tc (2.8MBq/cc) in the Jaszczak phantom, which was: (1) empty, (2) water-filled and (3) water-filled with low activity (0.1MBq/cc). The data was reconstructed with the Siemens's Flash3D iterative algorithm with 4 subsets and 8 iterations, attenuation-correction (AC) and scatter-correction (SC). DT modelling was based on the total spectrum counting rate. Sensitivity was assessed using AC-SC reconstructed SPECT data. Sensitivity and DT for the sources were 99.51±1.46cps/MBq and 0.60±0.04µs. For the phantom, sensitivity and DT were 109.9±2.3cps/MBq and 0.62±0.13µs. The recovery-coefficient varied from 5% for the 9.9mm, to 80% for the 31.2mm spheres. With our calibration methods, both sensitivity and DT constant of the SPECT camera had little dependence on the object geometry and attenuation. For small objects of known size, recovery-coefficient can be applied to correct PVE. Clinical quantitative SPECT appears to be possible and has many potential applications.

07 ISOTOPE AND RADIATION SOURCES↗