Systematic and random errors of PET-based 90 Y 3D dose quantification.

PURPOSE: The objective was to characterize both systematic and random errors in Positron Emission Tomography (PET)-based 90 Y three-dimensional (3D) dose quantification. METHODS: A modified NEMA-IEC phantom was used to emulate 90 Y-microsphere PET imaging conditions: sphere activity concentrations of 1.6 and 4.8 MBq/cc, sphere-to-background ratios of 4 and 13, and sphere diameters of 13, 17, and 37 mm. PET data were acquired using a GE D690 PET/CT scanner for 300 min on days 0-11. The data were downsampled to 60-5 min for multiple realizations to evaluate the count starvation effect. The image reconstruction algorithm was 3D-OSEM with PSF + TOF modeling; the parameters were optimized for dose-volume histogram (DVH), as a 90 Y 3D dose quantification. 90 Y-PET images were converted to dose maps using the local deposition method, then the sphere DVHs were calculated. The ground truth for the DVH was calculated using convolution method. Dose linearity was evaluated in decaying 90 Y activity (reduced count rate and total count) and decreasing acquisition durations (reduced total count only). Finally, the impacts of the low 32-ppm positron yield on PET-based 3D 90 Y-dose quantification were evaluated; the bias and variability of resulting DVHs were characterized. RESULTS: We observed nonlinear errors that depended on the 90 Y activity (count rate) and not on the total true prompt counts. These nonlinear errors in mean dose underestimated the measured mean dose by> 20% for a measured dose range of 40-230 Gy; although the shapes of the DVH were not altered. Compensation based on empirical models reduced the nonlinearity errors to be within 5% for measured dose range of 40-230 Gy. In contrast, the errors due to nonuniformity introduced by image noise dominated the systematic errors in the DVH and stretched the DVH on both tails. For the 37-mm sphere, the magnitude of errors in D80 increased from -25% to -36% when acquisition duration was decreased from 300 to 10 min. The effect of image noise on DVH was more extensive in smaller spheres; for the 17-mm sphere, the magnitude of errors in D80 increased from -29% to -45% acquisition duration was decreased from 300 to 10 min. For the 37-mm sphere, the errors in D20 increased from +3.5% to only +10.5% when the acquisition duration was decreased from 300 to 10 min; in the 17-mm sphere, the errors in D20 were 6.5% for both 300- and 10-min sphere images. CONCLUSIONS: Count-starved 90 Y-PET data introduce both systematic and random errors. The systematic error increases the apparent nonuniformity of the DVH, while the random error increases the uncertainty in the DVH. The systematic errors were larger than the random errors. Lower count rate of 90 Y-PET also introduces systematic bias, which is scanner specific. The errors of bias-compensated mean tumor dose were <10% when 90 Y-PET scan time was >15 min/bed for tumors >37 mm. Dmedian and Dmean were the most stable dose metrics. An acquisition duration of 30 min is recommended to keep the random errors < 10% for a typical tumor with sphere equivalent diameter >17 mm and average tumor dose >40 Gy.

Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases After Initial Peptide Receptor Radionuclide Therapy.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) and radioembolization are increasingly used in neuroendocrine neoplasms patients. However, concerns have been raised on cumulative hepatotoxicity. The aim of this sub-analysis was to investigate hepatotoxicity of yttrium-90 resin microspheres radioembolization in patients who were previously treated with PRRT. METHODS: Patients treated with radioembolization after systemic radionuclide treatment were retrospectively analysed. Imaging response according to response evaluation criteria in solid tumours (RECIST) v1.1 and clinical response after 3 months were collected. Clinical, biochemical and haematological toxicities according to common terminology criteria for adverse events (CTCAE) v4.03 were also collected. Specifics on prior PRRT, subsequent radioembolization treatments, treatments after radioembolization and overall survival (OS) were collected. RESULTS: Forty-four patients were included, who underwent a total of 58 radioembolization procedures, of which 55% whole liver treatments, at a median of 353 days after prior PRRT. According to RECIST 1.1, an objective response rate of 16% and disease control rate of 91% were found after 3 months. Clinical response was seen in 65% (15/23) of symptomatic patients after 3 months. Within 3 months, clinical toxicities occurred in 26%. Biochemical and haematological toxicities CTCAE grade 3-4 occurred in ≤ 10%, apart from lymphocytopenia (42%). Radioembolization-related complications occurred in 5% and fatal radioembolization-induced liver disease in 2% (one patient). A median OS of 3.5 years [95% confidence interval 1.8-5.1 years] after radioembolization for the entire study population was found. CONCLUSION: Radioembolization after systemic radionuclide treatments is safe, and the occurrence of radioembolization-induced liver disease is rare. LEVEL OF EVIDENCE: 4, case series.

Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases: International Multicenter Study on Efficacy and Toxicity.

PURPOSE: Radioembolization of liver metastases of neuroendocrine neoplasms (NEN) has shown promising results; however, the current literature is of limited quality. A large international, multicentre retrospective study was designed to address several shortcomings of the current literature. MATERIALS: 244 NEN patients with different NEN grades were included. METHODS: Primary outcome parameters were radiologic response 3 and 6 months after treatment according to RECIST 1.1 and mRECIST. Secondary outcome parameters included clinical response, clinical and biochemical toxicities. RESULTS: Radioembolization resulted in CR in 2%, PR in 14%, SD in 75% and PD 9% according to RECIST 1.1 and in CR in 8%, PR in 35%, SD in 48% and PD in 9% according to mRECIST. Objective response rates improved over time in 20% and 26% according to RECIST 1.1. and mRECIST, respectively. Most common new grade 3-4 biochemical toxicity was lymphocytopenia (6.7%). No unexpected clinical toxicities occurred. Radioembolization-specific complications occurred in < 4%. In symptomatic patients, improvement and resolution of symptoms occurred in 44% and 34%, respectively. Median overall survival from first radioembolization was 3.7, 2.7 and 0.7 years for G1, G2 and G3, respectively. Objective response is independent of NEN grade or primary tumour origin. Significant prognostic factors for survival were NEN grade/Ki67 index, ≥ 75% intrahepatic tumour load, the presence of extrahepatic disease and disease control rate according to RECIST 1.1. CONCLUSION: Safety and efficacy of radioembolization in NEN patients was confirmed with a high disease control rate of 91% in progressive patients and alleviation of NEN-related symptoms in 79% of symptomatic patients. LEVEL OF EVIDENCE: 4.

Effects of image noise, respiratory motion, and motion compensation on 3D activity quantification in count-limited PET images.

The aims of this study were to evaluate the effects of noise, motion blur, and motion compensation using quiescent-period gating (QPG) on the activity concentration (AC) distribution-quantified using the cumulative AC volume histogram (ACVH)-in count-limited studies such as 90Y-PET/CT. An International Electrotechnical Commission phantom filled with low 18F activity was used to simulate clinical 90Y-PET images. PET data were acquired using a GE-D690 when the phantom was static and subject to 1-4 cm periodic 1D motion. The static data were down-sampled into shorter durations to determine the effect of noise on ACVH. Motion-degraded PET data were sorted into multiple gates to assess the effect of motion and QPG on ACVH. Errors in ACVH at AC90 (minimum AC that covers 90% of the volume of interest (VOI)), AC80, and ACmean (average AC in the VOI) were characterized as a function of noise and amplitude before and after QPG. Scan-time reduction increased the apparent non-uniformity of sphere doses and the dispersion of ACVH. These effects were more pronounced in smaller spheres. Noise-related errors in ACVH at AC20 to AC70 were smaller (<15%) compared to the errors between AC80 to AC90 (>15%). The accuracy of ACmean was largely independent of the total count. Motion decreased the observed AC and skewed the ACVH toward lower values; the severity of this effect depended on motion amplitude and tumor diameter. The errors in AC20 to AC80 for the 17 mm sphere were -25% and -55% for motion amplitudes of 2 cm and 4 cm, respectively. With QPG, the errors in AC20 to AC80 of the 17 mm sphere were reduced to -15% for motion amplitudes <4 cm. For spheres with motion amplitude to diameter ratio >0.5, QPG was effective at reducing errors in ACVH despite increases in image non-uniformity due to increased noise. ACVH is believed to be more relevant than mean or maximum AC to calculate tumor control and normal tissue complication probability. However, caution needs to be exercised when using ACVH in post-therapy 90Y imaging because of its susceptibility to image degradation from both image noise and respiratory motion.

Practical reconstruction protocol for quantitative (90)Y bremsstrahlung SPECT/CT.

PURPOSE: To develop a practical background compensation (BC) technique to improve quantitative (90)Y-bremsstrahlung single-photon emission computed tomography (SPECT)/computed tomography (CT) using a commercially available imaging system. METHODS: All images were acquired using medium-energy collimation in six energy windows (EWs), ranging from 70 to 410 keV. The EWs were determined based on the signal-to-background ratio in planar images of an acrylic phantom of different thicknesses (2-16 cm) positioned below a (90)Y source and set at different distances (15-35 cm) from a gamma camera. The authors adapted the widely used EW-based scatter-correction technique by modeling the BC as scaled images. The BC EW was determined empirically in SPECT/CT studies using an IEC phantom based on the sphere activity recovery and residual activity in the cold lung insert. The scaling factor was calculated from 20 clinical planar (90)Y images. Reconstruction parameters were optimized in the same SPECT images for improved image quantification and contrast. A count-to-activity calibration factor was calculated from 30 clinical (90)Y images. RESULTS: The authors found that the most appropriate imaging EW range was 90-125 keV. BC was modeled as 0.53× images in the EW of 310-410 keV. The background-compensated clinical images had higher image contrast than uncompensated images. The maximum deviation of their SPECT calibration in clinical studies was lowest (<10%) for SPECT with attenuation correction (AC) and SPECT with AC + BC. Using the proposed SPECT-with-AC + BC reconstruction protocol, the authors found that the recovery coefficient of a 37-mm sphere (in a 10-mm volume of interest) increased from 39% to 90% and that the residual activity in the lung insert decreased from 44% to 14% over that of SPECT images with AC alone. CONCLUSIONS: The proposed EW-based BC model was developed for (90)Y bremsstrahlung imaging. SPECT with AC + BC gave improved lesion detectability and activity quantification compared to SPECT with AC only. The proposed methodology can readily be used to tailor (90)Y SPECT/CT acquisition and reconstruction protocols with different SPECT/CT systems for quantification and improved image quality in clinical settings.

A revised monitor source method for practical deadtime count loss compensation in clinical planar and SPECT studies.

The aim of the study is to verify the fundamental assumption in the monitor source method, i.e. uniform fractional count loss across the field of view (FOV), and to introduce a revised monitor source method for SPECT deadtime correction that minimally interferes with the clinical protocol. SPECT images of non-uniform phantoms (4GBq (99m)Tc) with and without monitor sources (2 × 20MBq (99m)Tc) attached to each detector were acquired nine times over 48 h in the photopeak energy window and the scatter energy window. Fractional count loss uniformity across the FOV was evaluated by correlating count rates in different regions of interest on projection images at different deadtime loss levels. The correction factors were calculated as the ratios of monitor source count rates with and without the phantom. Such factors were applied to the phantom images acquired without the monitor sources. The counting efficiency (count rate per unit activity) of the camera was calculated as a function of activity in the FOV both prior to and after the deadtime count-loss correction. The deadtime correction effectiveness was assessed by the independence of the efficiency on the activity in the FOV. Methods to interpolate the projection deadtime loss, based on limited projections, were also investigated. The fractional deadtime count loss was uniform across the FOV (r > 0.99). After the deadtime correction, the efficiency was largely independent of the activity in the FOV. The median and maximum absolute errors after the deadtime count loss correction were ≤1% and ~2%, respectively. Measured deadtime loss from five views per detector can be used to estimate deadtime count loss with errors ≤1% for all SPECT projections. The revised monitor source method can effectively correct planar and SPECT deadtime loss. Sparse sampling of the projection deadtime loss allows the acquisition of high monitor source counts with minimal time added while preserving the entire useful FOV.

Implications of CT noise and artifacts for quantitative 99mTc 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 (CTDIvol = 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 (99m)Tc SPECT images. These noise levels would be achieved at low CT dose levels (CTDIvol = 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 µ140 keV on the order of 10%, that in turn, could introduce errors on the order of ∼ 10% into the reconstructed (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 (CTDIvol ∼ 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.

MO-A-217BCD-02: Yttrium-90 Microsphere Therapy Planning and Dose Calculations.

Yttrium-90 microsphere therapy, a form of radiation therapy, is an increasingly popular option for care of patients with liver metastases or unresectable hepatocellular carcinoma. The therapy directly delivers Yttrium-90 microspheres via the hepatic artery to specifically targeted disease sites. Following Yttrium-90 microsphere therapy, a vast majority of Yttrium-90 microspheres preferentially lodge in neoplastic tissue due to their embolic size (mean diameter 32 μm) and targeted trans-arterial delivery. Once embolized the microspheres do not migrate but deposits up to 90% of its energy in the first 5 mm of tissue. Prior to Yttrium-90 microsphere therapy, a 99mTc-MAA examination is conducted to evaluate catheter placement and lung-shunt fraction. The lung shunt fraction and absorbed dose estimates for lung and liver that guide Yttrium-90 administered activity are based on nuclear medicine imaging. A review of the pre- and post-therapy imaging procedures underlying Yttrium-90 microsphere therapy will be presented. Calculation of the lung shunt fraction and dosimetry models to estimate radiation absorbed doses will be discussed. Radiation safety issues will be also be reviewed. LEARNING OBJECTIVES: 1. To understand the imaging sequence for Yttrium-90 microsphere therapy planning and dose calculations 2. To understand calculation of lung shunt fraction and estimation of absorbed dose for lung and liver 3. To become familiar with radiation safety and regulations surrounding Yttrium-90 microsphere therapy.

The local neutron flux at low Earth-orbiting altitudes.

The COMPTEL instrument onboard the Compton Gamma Ray Observatory (CGRO) has been used to measure the variation of the atmospheric neutron flux below 5 MeV as a function of vertical cutoff rigidity and spacecraft orientation at an altitude of 450 km. The instrumental 2.2 MeV background line, resulting from thermal neutron capture on hydrogen, was used for the measurement. The dependence of the 2.2 MeV rate on rigidity and geocentre zenith can be described by an analytic function: the line rate decreases linearly with geocentre zenith, and decreases exponentially with the vertical cutoff rigidity. The flux varies on average by about a factor of 3.7 between the extremes in rigidity, and by a factor of 1.7 between the extremes of spacecraft orientation with respect to the Earth. We believe that mass shielding is more important in attenuating the atmospheric albedo than as a source of secondary neutrons. The COMPTEL instrument is well suited for a long-duration study of the dependence of the neutron flux on the vertical cutoff rigidity and the solar cycle.