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A new 90Y SIR-Spheres delivery kit (SIROS D-vial and shield) has been introduced with a different physical form from the legacy V-Vial kit. Here, we establish the dose calibrator settings and exposure-rate–to–activity conversion factor to assay 90Y SIR-Spheres activity in the new SIROS kit. Methods: Eight D-vials with initial 90Y activities from 1.2 to 6.6 GBq within acrylic shields were assayed with dose calibrators and exposure-rate meters until activities decayed to approximately 0.1 GBq. The dose calibrator settings resulting in the lowest median activity errors and the best-fit slope of exposure rate versus activity were identified. Results: SIROS D-vial 90Y activity can be accurately and reliably estimated directly using setting 51 × 10 on both the CRC-15R and the CRC-55tR dose calibrators (errors within ±0.5%) and indirectly with an exposure-rate reading at 30 cm using conversion factor 0.664 ± 0.003 GBq/(mR/h) (R2 = 0.985). Conclusion: Dose calibrator settings and exposure-rate–to–activity conversion factor for 90Y activity assays with new SIROS kit should be updated from legacy V-Vial parameters to avoid an approximately 10% underestimation. [ABSTRACT FROM AUTHOR]

This article is intended to introduce nuclear medicine technologists (NMTs) to the nuances of radiopharmaceutical therapy clinical trials. Here, we outline the potential roles and responsibilities of the NMT in clinical trials and provide context on different aspects of radionuclide therapy. The regulatory process involving investigational therapeutic radiopharmaceuticals is seldom taught to NMT students, nor is it included in the entry-level nuclear medicine certification examinations. Often, NMTs must spend significant time preparing for therapeutic clinical trials on their own, using multiple academic sources, seeking advice from various health care professionals, and reviewing numerous trial-specific manuals to recognize the detailed requirements. The emergence of theranostics has spurred an increase in the development of therapeutic radiopharmaceuticals. Investigators with a robust nuclear medicine background are required to help develop successful therapeutic clinical trials, and well-informed NMTs are crucial to the success of such trials. This article follows a series of previous publications from the Society of Nuclear Medicine and Molecular Imaging Clinical Trials Network research series for technologists and is intended to guide the investigational radiopharmaceutical landscape. [ABSTRACT FROM AUTHOR]

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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. Molecular breast imaging (MBI) of 99mTc-sestamibi with dual-headed, pixelated, cadmium–zinc–telluride (CZT) detectors is increasingly used in breast cancer care for screening/detecting lesions, monitoring response to therapy, and predicting risk of cancer. MBI as a truly quantitative tool in these applications, however, is limited due the lack of absolute 99mTc-sestamibi uptake quantification. To help advance the field of quantitative MBI, we have developed a Monte Carlo simulation application of the GE Discovery NM 750b system. Methods. Our simulation consists of a two-step process using the Geant4 toolkit to model the detector and source geometry and to track photon interactions and a MATLAB script to model the charge transport within the pixelated CZT detector. Simulated detector and detector response model parameters were selected to match measured and simulated standard performance characteristics using various 99mTc point-, line-, and film-sources in air. The final model parameters were verified by comparing the count profiles, energy spectra, and region of interest counts between simulated and measured images of a breast phantom with two spherical lesions in 5 cm thick medium of air or water. Results. Final performance characteristics with 99mTc sources in air were: (1) energy resolution: 6.1% measured versus 5.9% simulated photopeak full-width at half-maximum (FWHM), (2) spatial resolution: mean error between measured and simulated FWHM of 0.08 mm across 4.4–14.0 mm FWHM range, and (3) sensitivity: 572 cpm/μCi measured versus 567 cpm/μCi simulated (<1% error). Good agreement was observed in the breast phantom line profiles through the spherical lesions and overall energy spectra, with <5% difference in sphere counts between simulated and measured data. Conclusion. A pixelated CZT charge transport and induction model was successfully implemented and validated to simulate imaging with the GE Discovery NM 750b system. This work will enable investigations improving MBI image quality and developing algorithms for uptake quantification. [ABSTRACT FROM AUTHOR]

The purpose of this study is to perform post-administration dosimetry in yttrium-90 radioembolization through micro-CT imaging of radiopaque microsphere distributions in a porcine renal model and explore the impact of spatial resolution of an imaging system on the extraction of specific dose metrics. Following the administration of radiopaque microspheres to the kidney of a hybrid farm pig, the kidney was explanted and imaged with micro-CT. To produce an activity distribution, 400 MBq of yttrium-90 activity was distributed throughout segmented voxels of the embolized vasculature based on an established linear relationship between microsphere concentration and CT voxel value. This distribution was down-sampled to coarser isotropic grids ranging in voxel size from 2.5 to 15 mm to emulate nominal resolutions comparable to those found in yttrium-90 PET and Bremsstrahlung SPECT imaging. Dose distributions were calculated through the convolution of activity distributions with dose-voxel kernels generated using the GATE Monte Carlo toolkit. Contours were computed to represent normal tissue and target volumes. Dose-volume histograms, dose metrics, and dose profiles were compared to a ground truth dose distribution computed with GATE. The mean dose to the target for all studied voxel sizes was found to be within 5.7% of the ground truth mean dose. was shown to be strongly correlated with image voxel size of the dose distribution (r2 = 0.90). is cited in the literature as an important dose metric and its dependence on voxel size suggests higher resolution dose distributions may provide new perspectives on dose-response relationships in yttrium-90 radioembolization. This study demonstrates that dose distributions with large voxels incorrectly homogenize the dose by attributing escalated doses to normal tissues and reduced doses in high-dose target regions. High-resolution micro-CT imaging of radiopaque microsphere distributions can provide increased confidence in characterizing the absorbed dose heterogeneity in yttrium-90 radioembolization. [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]

Objective: To compare "virtual" unenhanced (VUE) computed tomography (CT) images, reconstructed from rapid kVp-switching dual-energy computed tomography (DECT), to "true" unenhanced CT images (TUE), in clinical abdominal imaging. The ability to replace TUE with VUE images would have many clinical and operational advantages. Methods: VUE and TUE images of 60 DECT datasets acquired for standard-of-care CT of pancreatic cancer were retrospectively reviewed and compared, both quantitatively and qualitatively. Comparisons included quantitative evaluation of CT numbers (Hounsfield Units, HU) measured in 8 different tissues, and 6 qualitative image characteristics relevant to abdominal imaging, rated by 3 experienced radiologists. The observed quantitative and qualitative VUE and TUE differences were compared against boundaries of clinically relevant equivalent thresholds to assess their equivalency, using modified paired t-tests and Bayesian hierarchical modeling. Results: Quantitatively, in tissues containing high concentrations of calcium or iodine, CT numbers measured in VUE images were significantly different from those in TUE images. CT numbers in VUE images were significantly lower than TUE images when calcium was present (e.g. in the spine, 73.1 HU lower, p < 0.0001); and significantly higher when iodine was present (e.g. in renal cortex, 12.9 HU higher, p < 0.0001). Qualitatively, VUE image ratings showed significantly inferior depiction of liver parenchyma compared to TUE images, and significantly more cortico-medullary differentiation in the kidney. Conclusions: Significant differences in VUE images compared to TUE images may limit their application and ability to replace TUE images in diagnostic abdominal CT imaging. [ABSTRACT FROM AUTHOR]

Molecular breast imaging (MBI) is an increasingly recognized nuclear medicine imaging modality to detect breast lesions suspicious for malignancy. Recent advances have allowed the development of tissue sampling of MBI-detected lesions using a single-headed camera (breast-specific gamma imaging system) or a dual-headed camera system (MBI system). In this article, we will review current indications of MBI, differences of the two single- and dual-headed camera systems, the appropriate selection of biopsy equipment, billing considerations, and radiation safety. It will also include practical considerations and guidance on how to integrate MBI and MBI-guided biopsy in the current breast imaging workflow. [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]

The TheraSphere Global Dosimetry Steering Committee was formed in 2017 by BTG International to review existing data and address gaps in knowledge related to dosimetry. This committee is comprised of health care providers with diverse areas of expertise and perspectives on radiation dosimetry. The goal of these recommendations is to optimize glass microspheres radiation therapy for hepatocellular carcinoma while accounting for variables including disease presentation, tumour vascularity, liver function, and curative/palliative intent. The recommendations aim to unify glass microsphere users behind standardized dosimetry methodology that is simple, reproducible and supported by clinical data, with the overarching goal of improving clinical outcomes and advancing the knowledge of dosimetry. [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: To investigate hepatocellular carcinoma tumor dose-response characteristics based on voxel-level absorbed doses (D) and biological effective doses (BED) using quantitative 90Y-single-photon emission computed tomography (SPECT)/computed tomography (CT) after 90Y-radioembilization with glass microspheres. We also investigated the relationship between normal liver D and toxicities.Methods and Materials: 90Y-radioembolization activity distributions for 34 patients were based on quantitative 90Y-bremsstrahlung SPECT/CT. D maps were generated using a local-deposition algorithm. Contrast-enhanced CT or magnetic resonance imaging scans of the liver were registered to 90Y-SPECT/CT, and all tumors larger than 2.5 cm diameter (53 tumors) were segmented. Tumor mean D and BED (Dmean and BEDmean) and dose volume coverage from 0% to 100% in 10% steps (D0-D100 and BED0-BED100) were extracted. Tumor response was evaluated on follow-up using World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and modified RECIST (mRECIST) criteria. Differences in dose metrics for responders and nonresponders were assessed using the Mann-Whitney U test. A univariate logistic regression model was used to determine tumor dose metrics that correlated with tumor response. Correlations among tumor size, tumor Dmean, and tumor dose heterogeneity (defined as the coefficient of variation) were assessed.Results: The objective response rates were 14 of 53, 15 of 53, and 30 of 53 for WHO, RECIST, and mRECIST criteria, respectively. WHO and RECIST response statuses did not correlate with D or BED. For mRECIST responders and nonresponders, D and BED were significantly different for Dmean, D20 to D80, BEDmean, and BED0 to BED80. Threshold doses (and the 95% confidence interval) for 50% probability of mRECIST response (D50%) were 160 Gy (123-196 Gy) for Dmean and 214 Gy (146-280 Gy) for BEDmean. Tumor dose heterogeneity significantly correlated with tumor volume. No statistically significant association between Dmean to normal liver and complications related to bilirubin, albumin, or ascites was observed.Conclusions: Hepatocellular carcinoma tumor dose-response curves after 90Y-radioembolization with glass microspheres showed Dmean of 160 Gy and BEDmean of 214 Gy for D50% with a positive predictive value of ∼70% and a negative predictive value of ∼62%. No complications were observed in our patient cohort for normal liver Dmean less than 44 Gy. [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]

Continuous-bed-motion (CBM) acquisition mode has been made commercially available in PET/CT scanners. CBM mode is designed for whole-body imaging, with a long scan length (multiple axial fields of view [aFOVs]) and short acquisition duration (2-3 min/aFOV). PET/CT has recently been used after 90Y-microsphere therapy to quantify 90Y activity distribution in the liver. Here we compared counting efficiencies along the bed-motion direction (z-axis) between CBM and step-and-shoot (SS) acquisition modes for limited-view organ scans, such as 90Y PET/CT liver studies, that have short scan lengths (≤2 aFOVs) and long acquisition durations (10-30 min/aFOV). Methods: The counting efficiencies, that is, analytic sensitivities, in SS mode (single-aFOV and multiple-aFOV scans) and CBM mode were theoretically derived and experimentally validated using a cylindric 68Ge phantom. The sensitivities along the z-axis were compared between the SS and CBM modes. Results: The analytic and experimental count profiles were in good agreement, validating the analytic models. For fixed scan durations, the overall coincidence counting efficiency in CBM mode was lower (∼60%) than those in SS modes, and the maximum sensitivity in CBM mode was 50% or less of that in 1-aFOV SS mode and 100% or less of that in 2-aFOV SS mode. Conclusion: The ability of CBM mode to tailor-fit the PET/CT scan length and local scan duration is not realized in studies with a short scan length (≤30 cm) and long scan duration (20 min/aFOV for the scanner). SS acquisition mode is preferable to CBM mode for limited-view organ and count-starved scans, such as 90Y PET/CT liver scans, because of the higher counting efficiency of SS mode, which leads to better image quality and quantification precision. [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]

Background: Selective internal radiation therapy (SIRT) with yttrium-90 (90Y) resin microspheres is an established locoregional treatment option for unresectable hepatocellular carcinoma (HCC), which delivers a lethal dose of radiation to hepatic tumors, while sparing surrounding healthy tissue. DOORwaY90 is a prospective, multicenter, open-label, single arm study, designed to evaluate the safety and effectiveness of 90Y resin microspheres as first-line treatment in patients with unresectable/unablatable HCC. It is unique in that it is the first study with resin microspheres to utilize a personalized 90Y dosimetry approach, and independent review for treatment planning and response assessment.Methods: Eligibility criteria include unresectable/unablatable HCC, Barcelona Clinic Liver Cancer stage A, B1, B2, or C with a maximal single tumor diameter of ≤ 8 cm, and a sum of maximal tumor diameters of ≤ 12 cm, and at least one tumor ≥ 2 cm (long axis) per localized, modified Response Evaluation Criteria in Solid Tumors. Partition model dosimetry is used to determine the optimal dose; the target mean dose to tumor is ≥ 150 Gy. Patients are assessed at baseline and at regular intervals up until 12 months of treatment for response rates, safety, and quality of life (QoL). Post-treatment dosimetry is used to assess dose delivered to tumor and consider if retreatment is necessary. The co-primary endpoints are best objective response rate and duration of response. Secondary endpoints include grade ≥ 3 toxicity, QoL, and incidence of liver resection and transplantation post SIRT. Target recruitment is 100 patients.Discussion: The results of this trial should provide further information on the potential use of SIRT with 90Y resin microspheres as first-line therapy for unresectable HCC.Trial Registration: Clinicaltrials.gov; NCT04736121; date of 1st registration, January 27, 2021, https://clinicaltrials.gov/ct2/show/NCT04736121 . [ABSTRACT FROM AUTHOR]

Thirty-one consecutive patients were included in this study who were planned for parathyroidectomy due to primary hyperparathyroidism. They were studied with US, 4D-CT and dual-phase scintigraphy including SPECT/CT, and possible adenomas were identified in each imaging modality. Imaging data were quantified with US, CT and SPECT. Parathyroidectomies were performed as minimally invasive according to preoperative imaging findings. A total of 16 adenomas were found in 15 patients, and the surgery was negative in four patients. The imaging results were compared with each other and correlated to histology findings and blood biochemistry (S-Ca and P-PTH). Quantitative SPECT found a strong correlation between the quantification methods—Conjugate Gradient with Attenuation and Scatter Correction with a zone map (CGZAS) and Conjugate Gradient with Attenuation and Scatter Correction (CGAS)—measured as SUVmax and kBq/mL. However, a statistically significant correlation between the quantitative parameters (CGZAS and CGAS) and serum biomarkers (S-PTH and S-Ca) was not observed. The sensitivities of the imaging methods were calculated using histopathology as a gold standard. SPECT/CT demonstrated 93% sensitivity, 4D-CT 93% sensitivity and ultrasonography 73% sensitivity. The imaging methods were compared with each other using parathyroid regions because findings and locations varied between the modalities. Our prospective study supports that quantitative SPECT/CT is useful for presurgical assessment of primary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

Bone metastases are common in prostate cancer (PCa). Fluorocholine-18 (FCH) and sodium fluoride-18 (NaF) have been used to assess PCa associated skeletal disease in thousands of patients by demonstrating different mechanism of uptake-cell membrane (lipid) synthesis and bone mineralization. Here, this difference is characterized quantitatively in detail. Our study cohort consisted of 12 patients with advanced disease (> 5 lesions) (M) and of five PCa patients with no skeletal disease (N). They had routine PET/CT with FCH and NaF on consecutive days. Skeletal regions in CT were used to co-register the two PET/CT scans. Bone 3-D volume of interest (VOI) was defined on the CT of PET with a threshold of HU > 150, and sclerotic/dense bone as HU > 600, respectively. Additional VOIs were defined on PET uptake with the threshold values on both FCH (SUV > 3.5) and NaF (SUV > 10). The pathologic skeletal volumes for each technique (CT, HU > 600), NaF (SUV > 10) and FCH (SUV > 3.5) were developed and analyzed. The skeletal VOIs varied from 5.03 L to 7.31 L, whereas sclerotic bone VOIs were from 0.88 L to 2.99 L. Total choline kinase (cell membrane synthesis) activity for FCH (TCA) varied from 0.008 to 4.85 [kg] in M group and from 0.0006 to 0.085 [kg] in N group. Total accelerated osteoblastic (bone demineralization) activity for NaF (TBA varied from 0.25 to 13.6 [kg] in M group and varied from 0.000 to 1.09 [kg] in N group. The sclerotic bone volume represented only 1.86 ± 1.71% of the pathologic FCH volume and 4.07 ± 3.21% of the pathologic NaF volume in M group, and only 0.08 ± 0.09% and 0.18 ± 0.19% in N group, respectively. Our results suggest that CT alone cannot be used for the assessment of the extent of active metastatic skeletal disease in PCa. NaF and FCH give complementary information about the activity of the skeletal disease, improving diagnosis and disease staging. [ABSTRACT FROM AUTHOR]

Radioembolization is an established treatment for chemoresistant and unresectable liver cancers. Currently, treatment planning is often based on semi-empirical methods, which yield acceptable toxicity profiles and have enabled the large-scale application in a palliative setting. However, recently, five large randomized controlled trials using resin microspheres failed to demonstrate a significant improvement in either progression-free survival or overall survival in both hepatocellular carcinoma and metastatic colorectal cancer. One reason for this might be that the activity prescription methods used in these studies are suboptimal for many patients.In this review, the current dosimetric methods and their caveats are evaluated. Furthermore, the current state-of-the-art of image-guided dosimetry and advanced radiobiological modeling is reviewed from a physics’ perspective. The current literature is explored for the observation of robust dose-response relationships followed by an overview of recent advancements in quantitative image reconstruction in relation to image-guided dosimetry.This review is concluded with a discussion on areas where further research is necessary in order to arrive at a personalized treatment method that provides optimal tumor control and is clinically feasible. [ABSTRACT FROM AUTHOR]

We have previously developed a dual-energy digital mammography (DEDM) technique for calcification imaging under full-field imaging conditions using a commercially available flat-panel based digital mammography system. Although dual-energy (DE) imaging could suppress the obscuration of calcifications by tissue-structure background, it also increases the intrinsic noise in the DE images. Here we report on the effects of three different noise reduction techniques on DE calcification images: a simple smoothing (boxcar) filter applied to the DE image, a median filter applied to the HE image prior to the computation of the DE image and an adaptation of the Kalender's correlated-noise reduction (KNR) technique for DEDM. We compared the different noise reduction techniques by evaluating their effects on DE calcification images of a 5 cm thick breast-tissue-equivalent slab with continuously varying glandular-tissue ratio superimposed with calcium carbonate crystals of various sizes that simulate calcifications. Evaluations of different noise reducing techniques were performed by comparison of the root-mean-square signal in background regions (no calcifications present) of the DE calcification images and the contrast-to-noise ratios (CNR) of the calcifications in the DE calcification images. Amongst the different noise reduction techniques evaluated in this study, the KNR method was found to be most effective in reducing the image noise and increasing the calcification visibility (or CNR), closely followed by the HE median filter technique. Although the simple smoothing (boxcar) filter reduced the noise, it did not improve calcification visibility. The visible calcification threshold size with DEDM over smoothly varying background at screening mammography doses, assuming a CNR threshold of 4, was estimated to be around 250 µm with both the HE median filter and the KNR techniques. The quality of DE images with noise reduction techniques based on phantom studies were verified with DE images of an animal-tissue phantom that consisted of calcifications superimposed over more realistic tissue structures. [ABSTRACT FROM AUTHOR]