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Background: Current molecular breast imaging (MBI) images are limited to qualitative evaluation, not absolute measurement, of 99mTc uptake in benign and malignant breast tissues. Purpose: This work assesses the accuracy of previously‐published and newly‐proposed tumor and normal breast tissue 99mTc uptake MBI measurements using simulations of a commercial dual‐headed planar MBI system under typical clinical and acquisition protocols. Methods: Quantification techniques were tested in over 4000 simulated acquisitions of spherical and ellipsoid tumors with clinically relevant uptake conditions using a validated Monte Carlo application of the GE Discovery NM750b system. The evaluated techniques consisted of four tumor total activity methodologies (two single‐detector‐based and two geometric‐mean‐based), two tumor MBI volume methodologies (diameter‐based and ROI‐based), and two normal tissue activity concentration methodologies (single‐detector‐based and geometric‐mean‐based). The most accurate of these techniques were then used to estimate tumor activity concentrations and tumor to normal tissue relative activity concentrations (RC). Results: Single‐detector techniques for tumor total activity quantification achieved mean (standard deviation) relative errors of 0.2% (4.3%) and 1.6% (4.4%) when using the near and far detector images, respectively and were more accurate and precise than the measured 8.1% (5.8%) errors of a previously published geometric‐mean technique. Using these activity estimates and the true tumor volumes resulted in tumor activity concentration and RC errors within 10% of simulated values. The precision of tumor activity concentration and RC when using only MBI measurements were largely driven by the errors in estimating tumor MBI volume using planar images (± 30% inter‐quartile range). Conclusions: Planar MBI images were shown to accurately and reliably be used to estimate tumor total activities and normal tissue activity concentrations in this simulation study. However, volumetric tumor uptake measurements (i.e., absolute and relative concentrations) are limited by inaccuracies in MBI volume estimation using two‐dimensional images, highlighting the need for either tomographic MBI acquisitions or anatomical volume estimates for accurate three‐dimensional tumor uptake estimates. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the accuracy and biases of predicted lung shunt fraction (LSF) and lung dose (LD) calculations via 99mTc‐macro‐aggregated albumin (99mTc‐MAA) planar imaging for treatment planning of 90Y‐microsphere radioembolization. Methods and materials: LSFs in 52 planning and LDs in 44 treatment procedures were retrospectively calculated, in consecutive radioembolization patients over a 2 year interval, using 99mTc‐MAA planar and SPECT/CT imaging. For each procedure, multiple planar LSFs and LDs were calculated using different: (1) contours, (2) views, (3) liver 99mTc‐MAA shine‐through compensations, and (4) lung mass estimations. The accuracy of each planar‐based LSF and LD methodology was determined by calculating the median (range) absolute difference from SPECT/CT‐based LSF and LD values, which have been demonstrated in phantom and patient studies to more accurately and reliably quantify the true LSF and LD values. Results: Standard‐of‐care LSF using geometric mean of lung and liver contours had median (range) absolute over‐estimation of 4.4 percentage points (pp) (0.9 to 11.9 pp) from SPECT/CT LSF. Using anterior views only decreased LSF errors (2.4 pp median, −1.1 to +5.7 pp range). Planar LD over‐estimations decreased when using single‐view versus geometric‐mean LSF (1.3 vs. 2.6 Gy median and 7.2 vs. 18.5 Gy maximum using 1000 g lung mass) but increased when using patient‐specific versus standard‐man lung mass (2.4 vs. 1.3 Gy median and 11.8 vs. 7.2 Gy maximum using single‐view LSF). Conclusions: Calculating planar LSF from lung and liver contours of a single view and planar LD using that same LSF and 1000 g lung mass was found to improve accuracy and minimize bias in planar lung dosimetry. [ABSTRACT FROM AUTHOR]

Purpose: There are no published data on organ doses following intra‐hepatic‐arterial administration of 99mTc‐macroaggregated‐albumin (IHA 99mTc‐MAA) routinely used in 90Y‐radioembolization treatment planning to assess intra‐ and extra‐hepatic depositions and calculate lung‐shunt‐fraction (LSF). We propose a method to model the organ doses following IHA 99mTc‐MAA that incorporates three in vivo constituent biodistributions, the 99mTc‐MAA that escape the liver due to LSF, and the 99mTc‐MAA dissociation fraction (DF). Methods: The potential in vivo biodistributions for IHA 99mTc‐MAA are: Liver‐Only MAA with all activity sequestered in the liver (LSF = 0&DF = 0), Intravenous MAA with all activity transferred intravenously as 99mTc‐MAA (LSF = 1&DF = 0), and Intravenous Pertechnetate with all activity is transferred intravenously as 99mTc‐pertechnetate (LSF = 0&DF = 1). Organ doses for Liver‐Only MAA were determined using OLINDA/EXM 2.2, where liver was modeled as the source organ containing 99mTc‐MAA, while those for Intravenous MAA and Intravenous Pertechnetate were from ICRP 128. Organ doses for the general case can be determined as a weighted‐linear‐combination of the three constituent biodistributions depending on the LSF and DF. The maximum‐dose scenario was modeled by selecting the highest dose rate for each organ amongst the three constituent cases. Results: For Liver‐Only MAA, the liver as source organ received the highest dose at 98.6 and 126 mGy/GBq for the adult male and adult female phantoms, respectively; all remaining organs received <27 and <32 mGy/GBq. For Intravenous MAA, the lung as source organ received the highest dose at 66 and 97 mGy/GBq; all remaining organs received <16 and <21 mGy/GBq. The organ with the highest dose for Intravenous Pertechnetate was the upper‐large‐intestinal wall at 56 and 73 mGy/GBq; all remaining organs received <26 and <34 mGy/GBq. The liver and lung doses for the maximum‐dose scenario with 5 mCi (185 MBq) 99mTc‐MAA were estimated at 18.2 and 12.2 mGy, and 23.3 and 17.9 mGy, for the adult male and adult female phantoms, respectively. Conclusion: Organ dose estimates following IHA 99mTc‐MAA based on constituent biodistribution models and patient‐specific LSF and DF values have been derived. Liver and lung were the organs with highest dose, receiving at most 15–25 mGy in the maximum‐dose scenario, following 5 mCi IHA 99mTc‐MAA. [ABSTRACT FROM AUTHOR]

Purpose: 99mTc‐MAA‐SPECT/CT may be used in 90Y‐glass microsphere radioembolization treatment planning to assess perfused liver volumes and absorbed dose distributions. The partition model (PM) offers a more detailed planning dosimetry option beyond the single‐compartment model more traditionally used in 90Y radioembolization. As 90Y radioembolization treatments shift toward activities and doses that aim to achieve tumor control, accurate and reliable treatment planning dosimetry for both tumors and normal liver (NL) becomes more critical. In this work, we explore the accuracy and precision of 90Y dosimetry predictions from pretherapy 99mTc‐MAA and PM. Methods: Both PM and voxel dosimetry models were used to calculate tumor and NL mean doses using both planning 99mTc‐MAA and verification 90Y‐SPECT/CT in this retrospective analysis of hepatocellular carcinoma cases treated with glass microspheres (NCT01900002, n = 32). Linear regression models were developed at first access, and then later correct, the estimates by (a) 99mTc‐MAA for 90Y voxel dosimetry and (b) 99mTc‐MAA PM for voxel dosimetry, separately for both tumors and NL. Bland‐Altman analysis was then used to evaluate the accuracy and precision of the regression model predictions with the mean bias and 95% prediction intervals (PI, ±1.96σ). Two categories of cases were stratified (catheter matched vs catheter unmatched) by establishing the level of 99mTc‐MAA and 90Y catheter position alignment. Only catheter‐matched cases were included in the 99mTc‐MAA vs 90Y voxel dosimetry comparison, while all cases were used to compare dosimetry models (PM vs voxel). Results: Half (16/32) of cases were deemed catheter matched. 99mTc‐MAA could reliably predict NL doses in catheter‐matched cases after application of the linear model, with mean bias (PI) of −1% (±31%). PM was equivalent to voxel dosimetry for NL doses with mean bias (PI) of 0% (±1%). Even among catheter‐matched cases, 99mTc‐MAA planning for 90Y tumor voxel doses was poor, overestimating dose by an average of nearly 40%. Upon application of the linear model, 99mTc‐MAA predictions for 90Y tumor voxel dose were only minimally biased (−4%) but possessed very large PI (±104%). PM predictions for tumor voxel dose using the linear model also showed small bias (−6%) but maintained similarly high PI of ±90%. Cases with tumors representing a large majority (>80%) of the total tumor volume demonstrated the best scenarios for 99mTc‐MAA and PM tumor dose predictions, with mean biases (PI) of −3% (±53%) and −4% (±21%), respectively. Conclusion: The unconditional use of 99mTc‐MAA to predict 90Y dosimetry across all cases is not recommended due to: (a) demonstrated the risk of unmatched catheter positions between procedures, and (b) large bias and uncertainty in 99mTc‐MAA predictions in cases with matched catheter locations. However, NL voxel dose predictions with 99mTc‐MAA are clinically viable and either PM or voxel dosimetry can be used to produce equivalent predictions. Both 99mTc‐MAA and PM can provide tumor dose predictions with potential clinical utility, but only in catheter‐matched cases and with tumors comprising a clear majority (>80%) of the total tumor volume. These findings stratify the predictive fidelity of 99mTc‐MAA‐ and PM‐based treatment planning for 90Y dosimetry in improving treatment outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Current treatment planning for 90Y radioembolization estimates lung mean dose (LMD) by measuring the lung shunt fraction (LSF) from 99mTc‐macroaggregated albumin (MAA) planar imaging and assuming a 1‐kg lung mass. This methodology, however, overestimates LSF and LMD and could therefore unnecessarily limit the dose to target volume(s). We propose an improved LMD calculation that derives LSF from 99mTc‐MAA SPECT/CT and the patient‐specific lung mass from diagnostic chest CT. Furthermore, we investigated the errors in lung mass, LSF, and LMD arising from contour variability in patient data in order to estimate the precision of our proposed methodology. Methods: Our proposed LMD (LMDnew) calculation consisted of the following steps: (a) estimate liver counts from the MAA SPECT/CT liver contour; (b) estimate total lung counts by multiplying density (counts/g) from the MAA SPECT/CT left‐lung contour by the total lung mass (g) from the diagnostic CT lung contours; (c) compute LSFnew from liver and lung counts; (d) calculate LMDnew using LSFnew and the total lung mass from the diagnostic CT (Mnew). LMDnew, LSFnew, and Mnew estimates were compared to standard model values (LMDclin, LSFclin, and 1 kg, respectively) in 52 consecutive patients with hepatocellular carcinoma who underwent radioembolization using 90Y glass microspheres. The precision of our methodology was quantified by varying lung and liver contours in the same patient population and calculating the resulting relative errors in the liver count, lung count, and lung mass measurements. Results: The median Mnew was 839 g (range, 550–1178 g) for men and 731 g (range, 548–869 g) for women. The median LSFnew was 0.02 (range, 0.01–0.11), while the median LMDnew was 4.9 Gy (range, 0.3–25.5 Gy). Mnew, LSFnew, and LMDnew were significantly lower than Mclin, LSFclin, and LMDclin, with respective relative mean (±SD) differences of −20% (±16%) for Mnew, −63% (±15%) for LSFnew, and −53% (±23%) for LMDnew. The estimated 1‐sigma uncertainties in Mnew, LSFnew, and LMDnew were 9%, 10%, and 13%, respectively. Conclusions: We derived a method to calculate lung mass and LSF using routinely available diagnostic chest CT and 99mTc‐MAA SPECT/CT. More importantly, we systematically quantified the errors in our measurements to establish the precision of the estimated lung dose (13%). The proposed methodology provides a more accurate LMD and an estimate of its precision, which will improve treatment and retreatment planning for 90Y radioembolizations. [ABSTRACT FROM AUTHOR]

Purpose: 90Y‐microsphere radioembolization or selective internal radiation therapy is increasingly being used as a treatment option for tumors that are not candidates for surgery and external beam radiation therapy. Recently, volumetric 90Y‐dosimetry techniques have been implemented to explore tumor dose–response on the basis of 3D 90Y‐activity distribution from PET imaging. Despite being a theranostic study, the optimization of quantitative 90Y‐PET image reconstruction still uses the mean activity concentration recovery coefficient (RC) as the objective function, which is more relevant to diagnostic and detection tasks than is to dosimetry. The aim of this study was to optimize 90Y‐PET image reconstruction by minimizing errors in volumetric dosimetry via the dose volume histogram (DVH). We propose a joint optimization of the number of equivalent iterations (the product of the iterations and subsets) and the postreconstruction filtration (FWHM) to improve the accuracy of voxel‐level 90Y dosimetry. Methods: A modified NEMA IEC phantom was used to emulate clinically relevant 90Y‐PET imaging conditions through various combinations of acquisition durations, activity concentrations, sphere‐to‐background ratios, and sphere diameters. PET data were acquired in list mode for 300 min in a single‐bed position; we then rebinned the list mode PET data to 60, 45, 30, 15, and 5 min per bed, with 10 different realizations. Errors in the DVH were calculated as root mean square errors (RMSE) of the differences in the image‐based DVH and the expected DVH. The new optimization approach was tested in a phantom study, and the results were compared with the more commonly used objective function of the mean activity concentration RC. Results: In a wide range of clinically relevant imaging conditions, using 36 equivalent iterations with a 5.2‐mm filtration resulted in decreased systematic errors in volumetric 90Y dosimetry, quantified as image‐based DVH, in 90Y‐PET images reconstructed using the ordered subset expectation maximization (OSEM) iterative reconstruction algorithm with time of flight (TOF) and point spread function (PSF) modeling. Our proposed objective function of minimizing errors in DVH, which allows for joint optimization of 90Y‐PET iterations and filtration for volumetric quantification of the 90Y dose, was shown to be superior to conventional RC‐based optimization approaches for image‐based absorbed dose quantification. Conclusion: Our proposed objective function of minimizing errors in DVH, which allows for joint optimization of iterations and filtration to reduce errors in the PET‐based volumetric quantification 90Y dose, is relevant to dosimetry in therapy procedures. The proposed optimization method using DVH as the objective function could be applied to any imaging modality used to assess voxel‐level quantitative information. [ABSTRACT FROM AUTHOR]

Purpose: 90Y‐microsphere selective internal radiation therapy (90Y‐SIRT or 90Y‐radioembolization) is used in the management of unresectable liver tumors. 90Y‐SIRT presents a unique situation where the total 90Y activity inside the liver can be determined with high accuracy (> 95%). 90Y bremsstrahlung single‐photon emission computed tomography (SPECT)/computed tomography (CT) can be self‐calibrated to provide quantitative images that facilitate voxel‐level absorbed dose calculations. We investigated the effects of different approaches for 90Y‐SPECT self‐calibration on the quantification of absorbed doses following 90Y‐SIRT. Methods: 90Y bremsstrahlung SPECT/CT images of 31 patients with hepatocellular carcinoma, collected following 90Y‐SIRT, were analyzed, yielding 48 tumor and 31 normal liver contours. We validated the accuracy of absorbed doses calculated by a commercial software against those calculated using Monte Carlo‐based radiation transport. The software package was used to analyze the following definitions of SPECT volume of interest used for 90Y‐SPECT self‐calibration: (a) SPECT field‐of‐view (FOV), (b) chest‐abdomen contour, (c) total liver contour, (d) total liver contour expanded by 5 mm, and (e) total liver contour contracted by 5 mm. Linear correlation and Bland–Altman analysis were performed for tumor and normal liver tissue absorbed dose volume histogram metrics between the five different approaches for 90Y‐SPECT self‐calibration. Results: The mean dose calculated using the commercial software was within 3% of Monte Carlo for tumors and normal liver tissues. The tumor mean dose calculated using the chest‐abdomen calibration was within 2% of that calculated using the SPECT FOV, whereas the doses calculated using the total liver contour, expanded total liver contour, and contracted total liver contour were within 68%, 47%, and 107%, respectively, of doses calculated using the SPECT FOV. The normal liver tissue mean dose calculated using the chest‐abdomen contour was within 1.3% of that calculated using the SPECT FOV, whereas the doses calculated using the total liver contour, expanded total liver contour, and contracted total liver contour were within 73%, 50%, and 114%, respectively, of doses calculated using the SPECT FOV. Conclusions: The mean error of < 3% for commercial software can be considered clinically acceptable for 90Y‐SIRT dosimetry. Absorbed dose quantification using 90Y‐SPECT self‐calibration with the chest‐abdomen contour was equivalent to that calculated using the SPECT FOV, but self‐calibration with the total liver contour yielded substantially higher (~70%) dose values. The large biases revealed by our study suggest that consistent absorbed dose calculation approaches are essential when comparing 90Y‐SIRT dosimetry between different clinical studies. [ABSTRACT FROM AUTHOR]

Purpose We developed scatter and attenuation-correction techniques for quantifying images obtained with Molecular Breast Imaging (MBI) systems. Methods To investigate scatter correction, energy spectra of a 99mTc point source were acquired with 0-7-cm-thick acrylic to simulate scatter between the detector heads. System-specific scatter correction factor, k, was calculated as a function of thickness using a dual energy window technique. To investigate attenuation correction, a 7-cm-thick rectangular phantom containing 99mTc-water simulating breast tissue and fillable spheres simulating tumors was imaged. Six spheres 10-27 mm in diameter were imaged with sphere-to-background ratios (SBRs) of 3.5, 2.6, and 1.7 and located at depths of 0.5, 1.5, and 2.5 cm from the center of the water bath for 54 unique tumor scenarios (3 SBRs × 6 sphere sizes × 3 depths). Phantom images were also acquired in-air under scatter- and attenuation-free conditions, which provided ground truth counts. To estimate true counts, T, from each tumor, the geometric mean (GM) of the counts within a prescribed region of interest (ROI) from the two projection images was calculated as [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to develop and validate a mathematical model to describe narrow-beam attenuation of kilovoltage x-ray beams for the intended applications of half-value layer (HVL) and quarter-value layer (QVL) estimations, patient organ shielding, and computer modeling. Methods: An empirical model, which uses the Lambert W function and represents a generalized Lambert-Beer law, was developed. To validate this model, transmission of diagnostic energy x-ray beams was measured over a wide range of attenuator thicknesses [0.49-33.03 mm Al on a computed tomography (CT) scanner, 0.09-1.93 mm Al on two mammography systems, and 0.1-0.45 mm Cu and 0.49-14.87 mm Al using general radiography]. Exposure measurements were acquired under narrow-beam geometry using standard methods, including the appropriate ionization chamber, for each radiographic system. Nonlinear regression was used to find the best-fit curve of the proposed Lambert W model to each measured transmission versus attenuator thickness data set. In addition to validating the Lambert W model, we also assessed the performance of two-point Lambert W interpolation compared to traditional methods for estimating the HVL and QVL [i.e., semilogarithmic (exponential) and linear interpolation]. Results: The Lambert W model was validated for modeling attenuation versus attenuator thickness with respect to the data collected in this study (R2 > 0.99). Furthermore, Lambert W interpolation was more accurate and less sensitive to the choice of interpolation points used to estimate the HVL and/or QVL than the traditional methods of semilogarithmic and linear interpolation. Conclusions: The proposed Lambert W model accurately describes attenuation of both monoenergetic radiation and (kilovoltage) polyenergetic beams (under narrow-beam geometry). [ABSTRACT FROM AUTHOR]

An alternative to the conventional method of performing the AAPM Report 52 rotational uniformity and sensitivity test has been developed. In contrast to the conventional method in which a Co-57 sheet source is fastened to the collimator, this new point-source method acquires the images intrinsically using a Tc-99m point source placed near the isocenter of gantry rotation. As with the conventional method, the point-source method acquires 5×106 count flood images at four distinct gantry positions to calculate the maximum sensitivity variation (MSV)—a quantitative metric of rotational uniformity and sensitivity variation. The point-source method incorporates corrections for the decay of Tc-99m between acquisitions, the curvature in the image intensity due to variation in photon flux across the detector from a near-field source, and the source-to-detector distance variations between views. The raw point-source images were fitted with an analytic function in order to compute curvature- and distance-corrected images prior to analysis. Five independent MSV measurements were performed using both conventional and point-source methods on a single detector of a dual-headed SPECT system to estimate the precision of each method. The precision of the point-source method was further investigated by performing ten independent measurements of MSV on six different detectors. Correlation between the MSV calculated by the two methods was investigated by performing the test on nine different detectors using both methods. Different levels of sensitivity variations were also simulated on four detectors to generate 40 additional paired points for correlation analysis. The effect of the total image counts on the MSV estimated with the new method was evaluated by acquiring image sequences with 5×106, 10×106, and 20×106 count images. The MSV calculated using the conventional and point-source methods exhibited a high degree of correlation and consistency with equivalence. The precision of the point-source method (0.145%) is lower than the conventional method (0.04%) but sufficient to test MSV. No statistically significant dependence of MSV with the point-source method on the total image counts over a range of (5–20)×106 counts was observed. Curvature correction of the images prior to the generation of difference images renders images more conducive to qualitative inspection for structured, nonrandom patterns. The advantages of the new methodology are that multiple detectors of a gamma camera can be evaluated simultaneously which substantially reduces the time required for MSV testing and the reduced risk of accidental damage to the collimators and patient proximity detection system from having to mount a sheet source on each of the detectors. [ABSTRACT FROM AUTHOR]