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Purpose: To determine 6-month interim safety, effectiveness, and multimodal imageability of imageable glass microsphere yttrium-90 ( 90 Y) radioembolization for unresectable hepatocellular carcinoma (HCC) in a first-in-human trial., Materials and Methods: Imageable microspheres (Eye90 Microspheres; ABK Biomedical, Halifax, Nova Scotia, Canada), a U.S. Food and Drug Administration (FDA) Breakthrough-Designated Device consisting of glass radiopaque 90 Y microspheres visible on computed tomography (CT) and single photon emission CT (SPECT), were used to treat 6 subjects with unresectable HCC. Patients underwent selective (≤2 segments) treatment in a prospective open-label pilot trial. Key inclusion criteria included liver-only HCC, performance status ≤1, total lesion diameter ≤9 cm, and Child-Pugh A status. Prospective partition dosimetry was utilized. Safety (measured by Common Terminology Criteria for Adverse Events [CTCAE] v5), multimodal imageability on CT and SPECT, and 3- and 6-month imaging response by modified Response Evaluation Criteria in Solid Tumors on magnetic resonance (MR) imaging were evaluated., Results: Seven tumors in 6 subjects were treated and followed to 180 days. Administration success was 100%. Microsphere distribution measured by radiopacity on CT correlated with SPECT. Ninety-day target lesion complete response (CR) was observed in 3 of 6 subjects (50%) and partial response (PR) in 2 (33.3%). At 180 days, target lesion CR was maintained in 3 subjects (50%) and PR in 1 (16.7%). Two subjects could not be reassessed, having undergone intervening chemoembolization. All subjects reported adverse events (AEs), and 5 reported AEs related to treatment. There were no treatment-related Grade ≥3 AEs., Conclusions: Radioembolization using imageable microspheres was safe and effective in 6 subjects with unresectable HCC at 6-month interim analysis. Microsphere distribution by radiopacity on CT correlated with radioactivity distribution by SPECT, providing previously unavailable CT-based tumor targeting information., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: Pre-treatment [ 99m Tc]TcMAA-based radioembolization treatment planning using multicompartment dosimetry involves the definition of the tumor and normal tissue compartments and calculation of the prescribed absorbed doses. The aim was to compare the real-world utility of anatomic and [ 99m Tc]TcMAA-based segmentation of tumor and normal tissue compartments., Materials and Methods: Included patients had HCC treated by glass [ 90 Y]yttrium microspheres, ≥ 1 tumor, ≥ 3 cm diameter and [ 99m Tc]TcMAA SPECT/CT imaging before treatment. Segmentation was performed retrospectively using dedicated dosimetry software: (1) anatomic (diagnostic CT/MRI-based), and (2) [ 99m Tc]TcMAA threshold-based (i.e., using an activity-isocontour threshold). CT/MRI was co-registered with [ 99m Tc]TcMAA SPECT/CT. Logistic regression and Cox regression, respectively, were used to evaluate relationships between total perfused tumor absorbed dose (TAD) and objective response rate (ORR) and overall survival (OS). In a subset-analysis pre- and post-treatment dosimetry were compared using Bland-Altman analysis and Pearson's correlation coefficient., Results: A total of 209 patients were enrolled. Total perfused tumor and normal tissue volumes were larger when using anatomic versus [ 99m Tc]TcMAA threshold segmentation, resulting in lower absorbed doses. mRECIST ORR was higher with increasing total perfused TAD (odds ratio per 100 Gy TAD increase was 1.22 (95% CI: 1.01-1.49; p = 0.044) for anatomic and 1.19 (95% CI: 1.04-1.37; p = 0.012) for [ 99m Tc]TcMAA threshold segmentation. Higher total perfused TAD was associated with improved OS (hazard ratio per 100 Gy TAD increase was 0.826 (95% CI: 0.714-0.954; p = 0.009) and 0.847 (95% CI: 0.765-0.936; p = 0.001) for anatomic and [ 99m Tc]TcMAA threshold segmentation, respectively). For pre- vs. post-treatment dosimetry comparison, the average bias for total perfused TAD was + 11.5 Gy (95% limits of agreement: -227.0 to 250.0) with a strong positive correlation (Pearson's correlation coefficient = 0.80)., Conclusion: Real-world data support [ 99m Tc]TcMAA imaging to estimate absorbed doses prior to treatment of HCC with glass [ 90 Y]yttrium microspheres. Both anatomic and [ 99m Tc]TcMAA threshold methods were suitable for treatment planning., Trial Registration Number: NCT03295006., (© 2024. The Author(s).)

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., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

A new 90 Y 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 90 Y SIR-Spheres activity in the new SIROS kit. Methods: Eight D-vials with initial 90 Y 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 90 Y 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) ( R 2 = 0.985). Conclusion: Dose calibrator settings and exposure-rate-to-activity conversion factor for 90 Y activity assays with new SIROS kit should be updated from legacy V-Vial parameters to avoid an approximately 10% underestimation., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Personalized dosimetry improves overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with glass 90 Y radioembolization. This study evaluated personalized tumor dose (TD) as a predictor of OS, progression-free survival (PFS), and local duration of response (DOR) in patients with surgically unresectable HCC treated with resin 90 Y radioembolization., Patients and Methods: This prospective, single-center, single-arm clinical trial (NCT04172714) evaluated the efficacy of scout activity of resin 90 Y versus 99m Tc-MAA for treatment planning. A secondary aim of this study was to evaluate personalized dosimetry as a predictor of OS, PFS, and DOR. Partition dosimetry model was utilized for nonsegmental therapies with targeted TD >200 Gy and nontumoral liver dose <70 Gy. Single compartment dose of 200 Gy was used for segmentectomies. OS, PFS, and local DOR from 90 Y was estimated using Kaplan-Meier estimation with log-rank analysis used to determine predictors of prolonged survival., Findings: Thirty patients with treatment-naive HCC and 33 tumors (19 segmental and 14 nonsegmental) were included. Overall, 18 patients underwent segmental Y90-RE and 12 underwent non-segmental/lobar therapies. The mean 90 Y TD was 493 Gy. The median follow-up since enrollment into the study was 37 months. The mean OS was 32.2 months for the entire cohort. A total of 5 patients underwent orthotopic liver transplantation post 90 Y and were excluded from further survival analysis. The mean OS for the remainder of the cohort was 30.1 months (median not reached). The mean TD >250 Gy resulted in prolonged mean OS and PFS. The median local DOR was 32.7 months with mean TD 330 Gy predicting prolonged DOR., Interpretation: For patients with surgically unresectable HCC treated with resin 90 Y, there is mean TD threshold predicting prolonged OS, PFS, and local DOR. Therefore, there should be further emphasis on personalized dosimetry for optimization of patient outcomes., Competing Interests: Conflicts of interest and sources of funding: This study was jointly funded by Radiological Society of North America and Sirtex Medical Ltd. The study sponsors had no role in the design, data interpretation, or decision to publish this study. N.K. discloses he works as a consultant for Sirtex Medical Ltd. No other potential conflicts of interest relevant to this article exist., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Personalised multi-compartment dosimetry based on [ 99m Tc]Tc-MAA is a valuable tool for planning 90 Y radioembolization treatments. The establishment and effective application of dose-effect relationships in yttrium-90 ( 90 Y) radioembolization requires [ 99m Tc]Tc-MAA SPECT quantification ideally independent of clinical site. The purpose of this multi-centre phantom study was to evaluate inter-site variability of [ 99m Tc]Tc-MAA imaging and evaluate a standardised imaging protocol. Data was obtained from the TARGET study, an international, retrospective multi-centre study including 14 sites across 8 countries. The impact of imaging related factors was estimated using a NEMA IQ phantom (representing the liver), and a uniformly filled cylindrical phantom (representing the lungs). Imaging was performed using site-specific protocols and a standardized protocol. In addition, the impact of implementing key image corrections (scatter and attenuation correction) in the site-specific protocols was investigated. Inter-site dosimetry accuracy was evaluated by comparing computed Lung Shunt Fraction (LSF) measured using planar imaging of the cylindrical and NEMA phantom, and contrast recovery coefficient (CRC) measured using SPECT imaging of the NEMA IQ phantom., Results: Regarding the LSF, inter-site variation with planar site-specific protocols was minimal, as determined by comparing computed LSF between sites (interquartile range 9.6-10.1%). A standardised protocol did not improve variation (interquartile range 8.4-9.0%) but did improve mean accuracy compared to the site-specific protocols (5.0% error for standardised protocol vs 8.8% error for site-specific protocols). Regarding the CRC, inter-system variation was notable for site-specific SPECT protocols and could not be improved by the standardised protocol (CRC interquartile range for 37 mm sphere 0.5-0.7 and 0.6-0.8 respectively), however the standardised protocol did improve accuracy of sphere:background determination. Implementation of key image corrections did improve inter-site variation (CRC interquartile range for 37 mm sphere 0.6-0.7)., Conclusion: Eliminating sources of variability in image corrections between imaging protocols reduces inter-site variation in quantification. A standardised protocol was not able to improve consistency of LSF or CRC but was able to improve accuracy., (© 2024. The Author(s).)

Background: Current molecular breast imaging (MBI) images are limited to qualitative evaluation, not absolute measurement, of 99m Tc uptake in benign and malignant breast tissues., Purpose: This work assesses the accuracy of previously-published and newly-proposed tumor and normal breast tissue 99m Tc 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., (© 2023 American Association of Physicists in Medicine.)

Background: There is an increasing body of evidence indicating Y90 dose thresholds for tumor response and treatment-related toxicity. These thresholds are poorly studied in resin Y90, particularly in hepatocellular carcinoma (HCC)., Purpose: To evaluate the efficacy of prospective voxel-based dosimetry for predicting treatment response and adverse events (AEs) in patients with HCC undergoing resin-based Y90 radioembolization., Materials and Methods: This correlative study was based on a prospective single-arm clinical trial (NCT04172714), which evaluated the efficacy of low/scout (555 MBq) activity of resin-based Y90 for treatment planning. Partition model was used with goal of tumor dose (TD) > 200 Gy and non-tumoral liver dose (NTLD) < 70 Gy for non-segmental therapies. Single compartment dose of 200 Gy was used for segmentectomies. Prescribed Y90 activity minus scout activity was administered for therapeutic Y90 followed by Y90-PET/CT. Sureplan® (MIM Software, Cleveland, OH) was used for dosimetry analysis. Treatment response was evaluated at 3 and 6 months. Receiver operating characteristic curve determined TD response threshold for objective response (OR) and complete response (CR) as well as non-tumor liver dose (NTLD) threshold that predicted AEs., Results: N = 30 patients were treated with 33 tumors (19 segmental and 14 non-segmental). One patient died before the first imaging, and clinical follow-up was excluded from this analysis. Overall, 26 (81%) of the tumors had an OR and 23 (72%) had a CR. A mean TD of 253 Gy predicted an OR with 92% sensitivity and 83% specificity (area under the curve (AUC = 0.929, p < 0.001). A mean TD of 337 Gy predicted a CR with 83% sensitivity and 89% specificity (AUC = 0.845, p < 0.001). A mean NTLD of 81 and 87 Gy predicted grade 3 AEs with 100% sensitivity and 100% specificity in the non-segmental cohort at 3- and 6-month post Y90, respectively., Conclusion: In patients with HCC undergoing resin-based Y90, there are dose response and dose toxicity thresholds directly affecting outcomes., Clinical Trial Number: NCT04172714., (© 2023. The Author(s).)

Purpose: In light of recently published clinical reports and trials, the TheraSphere Global Dosimetry Steering Committee (DSC) reconvened to review new data and to update previously published clinical and dosimetric recommendations for the treatment of hepatocellular carcinoma (HCC)., Methods: The TheraSphere Global DSC is comprised of health care providers across multiple disciplines involved in the treatment of HCC with yttrium-90 (Y-90) glass microsphere-based transarterial radioembolization (TARE). Literature published between January 2019 and September 2021 was reviewed, discussed, and adjudicated by the Delphi method. Recommendations included in this updated document incorporate both the results of the literature review and the expert opinion and experience of members of the committee., Results: Committee discussion and consensus led to the expansion of recommendations to apply to five common clinical scenarios in patients with HCC to support more individualized efficacious treatment with Y-90 glass microspheres. Existing clinical scenarios were updated to reflect recent developments in dosimetry approaches and broader treatment paradigms evolving for patients presenting with HCC., Conclusion: Updated consensus recommendations are provided to guide clinical and dosimetric approaches for the use of Y-90 glass microsphere TARE in HCC, accounting for disease presentation, tumor biology, and treatment intent., (© 2022. The Author(s).)

Purpose: To compare the accuracy and safety of 0.56 GBq resin yttrium-90 ( 90 Y) (scout 90 Y) microspheres with those of technetium-99m macroaggregated albumin (MAA) in predicting the therapeutic 90 Y (Rx 90 Y) dose for patients with hepatocellular carcinoma (HCC)., Materials and Methods: This prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout 90 Y. Rx 90 Y activity was administered 3 days after mapping. Using paired t test and Pearson correlation, the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), predicted mean tumor dose (TD), and nontumoral liver dose (NTLD) by MAA and scout 90 Y were compared with those by Rx 90 Y. Bland-Altman plots compared the level of agreement between the TNR and LSF of scout 90 Y and MAA with that of Rx 90 Y. The safety of scout 90 Y was evaluated by examining the discrepancy in extrahepatic activity between MAA and scout 90 Y., Results: Thirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx 90 Y. Scout 90 Y had a moderate LSF, strong TNR, strong TD, and very strong NTLD in correlation with those of Rx 90 Y. Furthermore, the TNR and LSF of scout 90 Y had a stronger agreement with those of Rx 90 Y than with those of MAA. In the nonsegmental subgroup, MAA had no significant correlation with the TD and NTLD of Rx 90 Y, whereas scout 90 Y had a very strong correlation with both of these factors. In the segmental subgroup, both MAA and scout 90 Y had a strong linear correlation with the TD and NTLD of Rx 90 Y., Conclusions: Compared with MAA, scout 90 Y is a more accurate surrogate for Rx 90 Y biodistribution for nonsegmental therapies., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the accuracy and biases of predicted lung shunt fraction (LSF) and lung dose (LD) calculations via 99m Tc-macro-aggregated albumin ( 99m Tc-MAA) planar imaging for treatment planning of 90 Y-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 99m Tc-MAA planar and SPECT/CT imaging. For each procedure, multiple planar LSFs and LDs were calculated using different: (1) contours, (2) views, (3) liver 99m Tc-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., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Background: Superficial inguinal (groin) vascularized lymph node transplantation is the most common option for the treatment of lymphedema, particularly in combination with free abdominal flap breast reconstruction. This study examines the utility of single-photon emission computed tomographic (SPECT/CT) lymphoscintigraphy for lower extremity reverse lymphatic mapping in presurgical planning for groin vascularized lymph node transplantation and appraises the physiologic lymphatic drainage to the superficial inguinal lymph nodes., Methods: All patients who underwent bilateral lower extremity SPECT/CT reverse lymphatic mapping over a 5-year period were included. Retrospective case note analysis was performed to collect demographic, surgical, and outcomes data., Results: The study included 84 patients; 56 of these subsequently underwent groin vascularized lymph node transplantation (58 flaps). Fifty-four of these flaps were combined with free abdominal flaps for breast reconstruction (55 flaps). Using SPECT/CT reverse lymphatic mapping investigation of 168 inguinal regions, drainage to at least one superficial inguinal region was visualized in 38.1 percent of patients; in 13.1 percent, drainage was visualized to both superficial inguinal regions. Using this information for presurgical planning, groin vascularized lymph node flap harvest was performed from the contralateral side in 57 of 58 cases (98.3 percent) using intraoperative gamma probe guidance, and no patient developed donor lower extremity lymphedema during follow-up (mean ± SD, 34.5 ± 15.4 months)., Conclusions: The authors' use of presurgical SPECT/CT reverse lymphatic mapping together with limited flap dissection and intraoperative gamma probe guidance resulted in no clinical cases of iatrogenic donor lower extremity lymphedema. The high incidence of drainage from the lower extremity to the superficial inguinal region mandates the use of reverse lymphatic mapping when performing groin vascularized lymph node transplantation., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Purpose: To develop a multidisciplinary consensus for high quality multidisciplinary implementation of brachytherapy using Yttrium-90 ( 90 Y) microspheres transarterial radioembolization ( 90 Y TARE) for primary and metastatic cancers in the liver., Methods and Materials: Members of the American Brachytherapy Society (ABS) and colleagues with multidisciplinary expertise in liver tumor therapy formulated guidelines for 90 Y TARE for unresectable primary liver malignancies and unresectable metastatic cancer to the liver. The consensus is provided on the most recent literature and clinical experience., Results: The ABS strongly recommends the use of 90 Y microsphere brachytherapy for the definitive/palliative treatment of unresectable liver cancer when recommended by the multidisciplinary team. A quality management program must be implemented at the start of 90 Y TARE program development and follow-up data should be tracked for efficacy and toxicity. Patient-specific dosimetry optimized for treatment intent is recommended when conducting 90 Y TARE. Implementation in patients on systemic therapy should account for factors that may enhance treatment related toxicity without delaying treatment inappropriately. Further management and salvage therapy options including retreatment with 90 Y TARE should be carefully considered., Conclusions: ABS consensus for implementing a safe 90 Y TARE program for liver cancer in the multidisciplinary setting is presented. It builds on previous guidelines to include recommendations for appropriate implementation based on current literature and practices in experienced centers. Practitioners and cooperative groups are encouraged to use this document as a guide to formulate their clinical practices and to adopt the most recent dose reporting policies that are critical for a unified outcome analysis of future effectiveness studies., Competing Interests: Conflicts of Interest Dr. Sharma received honoraria, research grant, and is a consultant for SIRTEX Medical Inc. Dr. Kappadath received honoraria and research funding from Boston Scientific, SIRTEX Medical, and ABK Biomedical. Dr. Choung received honoraria from SIRTEX Medical Inc. Dr Jabbour is a consultant for Merck & Co Inc; Syntactx, IMX Medical; and has grant funding from the NIH and Merck & Co, Inc. Dr Jeyarajah is a consultant for Angiodynamics, SIRTEX Medical Inc., Ethicon. Dr. Liu is a consultant for SIRTEX Medical Inc, Eisai Pharmaceuticals, and a speaker for Astra Zeneca and Eisa Pharmaceuticals. Dr. Meyer has a research grant and honorarium from Varian Medical Systems. Dr. Mikell has a research grant funding from Varian. Dr. Patel is a consultant to SIRTEX Medical and Medtronic Inc. and a speaker for Boston Scientific. Drs. Folkert, Kennedey, Gibbs, Yang, and Mourtada report no conflict of interest., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose : Molecular breast imaging (MBI) is used clinically to visualize the uptake of 99m Tc-sestamibi in breast cancers. Here, we use Monte Carlo simulations to develop a methodology to estimate tumor diameter in focal lesions and explore a semi-automatic implementation for clinical data. Methods : A validated Monte Carlo simulation of the GE Discovery NM 750b was used to simulate >75,000 unique spherical/ellipsoidal tumor, normal breast, and image acquisition conditions. Subsets of this data were used to 1) characterize the dependence of the full-width at half-maximum (FWHM) of a tumor profile on tumor, normal breast, and acquisition conditions, 2) develop a methodology to estimate tumor diameters, and 3) quantify the diameter accuracy in a broad range of clinical conditions. Finally, the methodology was implemented in patient images and compared to diameter estimates from physician contours on MBI, mammography, and ultrasound imaging. Results : Tumor profile FWHM was determined be linearly dependent on tumor diameter but independent of other factors such as tumor shape, uptake, and distance from the detector. A linear regression was used to calculate tumor diameter from the FWHM estimated from a background-corrected profile across a tumor extracted from a median-filtered single-detector MBI image, i.e., diameter = 1.2 mm + 1.2 × FWHM, for FWHM ≥ 13 mm. Across a variety of simulated clinical conditions, the mean error of the methodology was 0.2 mm (accuracy), with >50% of cases estimated within 1-pixel width of the truth (precision). In patient images, the semi-automatic methodology provided the longest diameter in 94% (60/64) of cases. The estimated true diameters, for oval lesions with homogeneous uptake, differed by ± 5 mm from physician measurements. Conclusion : This work demonstrates the feasibility of accurately quantifying tumor diameter in clinical MBI, and to our knowledge, is the first to explore its implementation and application in patient data., (© 2022 IOP Publishing Ltd.)

Purpose: There are no published data on organ doses following intra-hepatic-arterial administration of 99m Tc-macroaggregated-albumin (IHA 99m Tc-MAA) routinely used in 90 Y-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 99m Tc-MAA that incorporates three in vivo constituent biodistributions, the 99m Tc-MAA that escape the liver due to LSF, and the 99m Tc-MAA dissociation fraction (DF)., Methods: The potential in vivo biodistributions for IHA 99m Tc-MAA are: Liver-Only MAA with all activity sequestered in the liver (LSF = 0&DF = 0), Intravenous MAA with all activity transferred intravenously as 99m Tc-MAA (LSF = 1&DF = 0), and Intravenous Pertechnetate with all activity is transferred intravenously as 99m Tc-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 99m Tc-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) 99m Tc-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 99m Tc-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 99m Tc-MAA., (© 2022 American Association of Physicists in Medicine.)

Purpose: To investigate the relationships between tumor absorbed dose (TAD) or normal tissue absorbed dose (NTAD) and clinical outcomes in hepatocellular carcinoma (HCC) treated with yttrium-90 glass microspheres., Methods: TARGET was a retrospective investigation in 13 centers across eight countries. Key inclusion criteria: liver-dominant HCC with or without portal vein thrombosis, < 10 tumors per lobe (at least one ≥ 3 cm), Child-Pugh stage A/B7, BCLC stages A-C, and no prior intra-arterial treatment. Multi-compartment pre-treatment dosimetry was performed retrospectively. Primary endpoint was the relationship between ≥ grade 3 hyperbilirubinemia (such that > 15% of patients experienced an event) without disease progression and NTAD. Secondary endpoints included relationships between (1) objective response (OR) and TAD, (2) overall survival (OS) and TAD, and (3) alpha fetoprotein (AFP) and TAD., Results: No relationship was found between NTAD and ≥ grade 3 hyperbilirubinemia, which occurred in 4.8% of the 209 patients. The mRECIST OR rate over all lesions was 61.7%; for the target (largest) lesion, 70.8%. Responders and non-responders had geometric mean total perfused TADs of 225.5 Gy and 188.3 Gy (p = 0.048). Probability of OR was higher with increasing TAD (p = 0.044). Higher TAD was associated with longer OS (HR per 100 Gy increase = 0.83, 95% CI: 0.71-0.95; p = 0.009). Increased TAD was associated with higher probability of AFP response (p = 0.046 for baseline AFP ≥ 200 ng/mL)., Conclusion: Real-world data confirmed a significant association between TAD and OR, TAD and OS, and TAD and AFP response. No association was found between ≥ grade 3 hyperbilirubinemia and NTAD., Trial Registration Number: NCT03295006., (© 2022. The Author(s).)

Background: Selective internal radiation therapy (SIRT) with yttrium-90 ( 90 Y) 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 90 Y 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 90 Y 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 90 Y 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 ., (© 2022. The Author(s).)

Purpose: To perform precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model and to compare extracted dose metrics to those produced from conventional PET-based dosimetry., Materials and Methods: A CT calibration phantom was designed containing posts with nominal microsphere concentrations of 0.5 mg/mL, 5.0 mg/mL, and 25.0 mg/mL. The mean Hounsfield unit was extracted from the post volumes to generate a calibration curve to relate Hounsfield units to microsphere concentration. A nominal bolus of 40 mg of microspheres was administered to the livers of eight rabbits, followed by PET/CT imaging. A CT-based activity distribution was calculated through the application of the calibration curve to the CT liver volume. Post-treatment dosimetry was performed through the convolution of yttrium-90 dose-voxel kernels and the PET- and CT-based cumulated activity distributions. The mean dose to the liver in PET- and CT-based dose distributions was compared through linear regression, ANOVA, and Bland-Altman analysis., Results: A linear least-squares fit to the average Hounsfield unit and microsphere concentration data from the calibration phantom confirmed a strong correlation (r 2  > 0.999) with a slope of 14.13 HU/mg/mL. A poor correlation was found between the mean dose derived from CT and PET (r 2  = 0.374), while the ANOVA analysis revealed statistically significant differences (p < 10 -12 ) between the MIRD-derived mean dose and the PET- and CT-derived mean dose. Bland-Altman analysis predicted an offset of 15.0 Gy between the mean dose in CT and PET. The dose within the liver was shown to be more heterogeneous in CT than in PET with an average coefficient of variation equal to 1.99 and 1.02, respectively., Conclusion: The benefits of a CT-based approach to post-treatment dosimetry in yttrium-90 radioembolization include improved visualization of the dose distribution, reduced partial volume effects, a better representation of dose heterogeneity, and the mitigation of respiratory motion effects. Post-treatment CT imaging of radiopaque microspheres in yttrium-90 radioembolization provides the means to perform precision dosimetry and extract accurate dose metrics used to refine the understanding of the dose-response relationship, which could ultimately improve future patient outcomes., (© 2022. The Author(s).)

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.

Radioembolization, also known as selective internal radiation therapy (SIRT), is an established treatment for the management of patients with unresectable liver tumors. Advances in liver dosimetry and new knowledge about tumor dose-response relationships have helped promote the well-tolerated use of higher prescribed doses, consequently transitioning radioembolization from palliative to curative therapy. Lung dosimetry, unfortunately, has not seen the same advances in dose calculation methodology and renewed consensus in dose limits as normal liver and tumor dosimetry. Therefore, the efficacy of curative radioembolization may be compromised in patients where the current lung dose calculations unnecessarily limit the administered activity. The field is thus at a stage where a systematic review and update of lung dose limits is necessary to advance the clinical practice of radioembolization. This work summarizes the historical context and literature for origins of the current lung dose limits following radioembolization, that is, the 25-year-old, single institution, small patient cohort series that helped establish the lung shunt fraction and dose limits. Newer clinical evidence based on larger patient cohorts that challenges the historical data on lung dose limits are then discussed. We conclude by revisiting the rationale for current lung dose limits and by proposing a staged approach to advance the field of lung dosimetry and thus the practice of radioembolization as a whole., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The most common cause of death in advanced/metastatic hepatocellular carcinoma (HCC) is liver failure due to tumor progression. While retrospective studies and meta-analyses of systemic therapy combined with liver-directed therapy have been performed, prospective studies of safety/efficacy of antiangiogenesis followed by intra-arterial therapies are lacking. We tested our hypothesis that sorafenib followed by yttrium 90 glass microspheres ( 90 Y GMs) is safe and that survival outcomes may improve by controlling hepatic tumors., Methods: We enrolled 38 Child-Pugh A patients with advanced/metastatic HCC. In sum, 34 received sorafenib, followed after 4 weeks by 90 Y GMs. Analysis of safety and survival outcomes was performed to assess adverse events, median progression-free survival, and overall survival., Results: A total of 34 patients were evaluable: 14 (41.2%) with chronic hepatitis, nine (26.5%) with vascular invasion, and eleven (32.4%) with extrahepatic diseases. Safety analysis revealed that the combination therapy was well tolerated. Grade III-IV adverse events comprised fatigue (n=3), diarrhea (n=2), nausea (n=1), vomiting (n=2), hypertension (n=4), thrombocytopenia (n=1), hyperbilirubinemia (n=1), proteinuria (n=1), hyponatremia (n=1), and elevated alanine or aspartate aminotransferase (n=5). Median progression-free and overall survival were 10.4 months (95% CI 5.8-14.4) and 13.2 months (95% CI 7.9-18.9), respectively. Twelve patients (35.3%) achieved partial responses and 16 (47.0%) stable disease. Median duration of sorafenib was 20 (3-90) weeks, and average dose was 622 (466-800) mg daily. Dosimetry showed similar mean doses between planned and delivered calculations to normal liver and tumor:normal liver uptake ratio, with no significant correlation with adverse events at 3 and 6 months post- 90 Y treatment., Conclusion: This is the first prospective study to evaluate sorafenib followed by 90 Y in patients with advanced HCC. The study validated our hypothesis of safety with encouraging efficacy signals of the sequencing treatment, and provides proof of concept for future combination modalities for patients with advanced or metastatic HCC., Clinical Trial Registration Number: NCT01900002., Competing Interests: SCK has received research grants from Boston Scientific and ABK Biomedical and served as a consultant for Sirtex Medical, Boston Scientific, ABK Biomedical, and Terumo Medical. JK reports personal fees from Johnson and Johnson, Boston Scientific and grants from LungLife AI outside the submitted work. AM reports grants and personal fees from BTG, Sirtex Medical, and ABK Biomedical outside the submitted work. The authors declare no other potential conflicts of interest., (© 2021 Kaseb et al.)

Purpose . Molecular breast imaging (MBI) of 99m Tc-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 99m Tc-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 99m Tc 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 99m Tc 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/ μ Ci measured versus 567 cpm/ μ Ci 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., (© 2021 Institute of Physics and Engineering in Medicine.)

Purpose: A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 ( 90 Y)-resin microspheres., Methods: A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90 Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%-79%, no agreement ≤ 49%)., Results: Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99m Tc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90 Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100-120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90 Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement)., Conclusion: Practitioners are encouraged to work towards adoption of these recommendations.

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.D70was shown to be strongly correlated with image voxel size of the dose distribution ( r 2  = 0.90).D70is 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., (© 2021 Institute of Physics and Engineering in Medicine.)

Radioembolization, also known as selective internal radiation therapy (SIRT), is firmly established in the management of patients with unresectable liver cancers. Advances in normal and tumor liver dosimetry and new knowledge about tumor dose response relationships have helped promote the safe use of higher prescribed doses, consequently transitioning radioembolization from palliative to curative therapy. The lungs are considered a critical organ of risk for radioembolization treatment planning. Unfortunately, lung dosimetry has not achieved similar advances in dose calculation methodology as liver dosimetry. Current estimations of lung dose are dependent on a number of parameters associated with data acquisition and processing algorithms, leading to poor accuracy and precision. Therefore, the efficacy of curative radioembolization may be compromised in patients for whom the lung dose derived using currently available methods unnecessarily limits the desired administered activity to the liver. We present a systematic review of the various methods of determining the lung shunt fraction (LSF) and lung mean dose (LD). This review encompasses pretherapy estimations and post-therapy assessments of the LSF and LD using both 2D planar and 3D SPECT/CT based calculations. The advantages and limitations of each of these methods are deliberated with a focus on accuracy and practical considerations. We conclude the review by presenting a lexicon to precisely describe the methodology used for the estimation of LSF and LD; specifically, category, agent, modality, contour and algorithm, in order to aid in their interpretation and standardization in routine clinical practice.

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.

Purpose: 99m Tc-MAA-SPECT/CT may be used in 90 Y-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 90 Y radioembolization. As 90 Y 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 90 Y dosimetry predictions from pretherapy 99m Tc-MAA and PM., Methods: Both PM and voxel dosimetry models were used to calculate tumor and NL mean doses using both planning 99m Tc-MAA and verification 90 Y-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) 99m Tc-MAA for 90 Y voxel dosimetry and (b) 99m Tc-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 99m Tc-MAA and 90 Y catheter position alignment. Only catheter-matched cases were included in the 99m Tc-MAA vs 90 Y 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. 99m Tc-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, 99m Tc-MAA planning for 90 Y tumor voxel doses was poor, overestimating dose by an average of nearly 40%. Upon application of the linear model, 99m Tc-MAA predictions for 90 Y 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 99m Tc-MAA and PM tumor dose predictions, with mean biases (PI) of -3% (±53%) and -4% (±21%), respectively., Conclusion: The unconditional use of 99m Tc-MAA to predict 90 Y 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 99m Tc-MAA predictions in cases with matched catheter locations. However, NL voxel dose predictions with 99m Tc-MAA are clinically viable and either PM or voxel dosimetry can be used to produce equivalent predictions. Both 99m Tc-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 99m Tc-MAA- and PM-based treatment planning for 90 Y dosimetry in improving treatment outcomes., (© 2020 American Association of Physicists in Medicine.)

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., Competing Interests: CSN is a consultant to GE Healthcare. This study was funded by GE Healthcare. The other authors have declared that no competing interests exist. The commercial funder, General Electric Healthcare, does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: To assess the overall survival (OS) and progression-free survival (PFS) of unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass-microsphere transarterial radioembolization (TARE) with and without concurrent sorafenib., Methods: OS and PFS were analyzed in 55 patients with an intrahepatic tumor (IHT) ≤50% without advanced or aggressive disease features (ADFs), which was referred to presence of infiltrative/ill-defined HCC, macrovascular invasion, or extrahepatic disease treated with only TARE (TARE&#95;alone) and in 74 patients with IHT ≤50% with ADFs or IHT >50% treated with TARE and sorafenib (TARE&#95;sorafenib). Prognostic factors for OS and PFS were identified using univariate and multivariate analyses., Results: Median OS and PFS of TARE&#95;alone patients were 21.6 (95% CI 6.1-37.1) and 9.1(95% CI 5.2-13.0) months, respectively, and for TARE&#95;sorafenib patients 12.4 (95% CI 9.1-15.6) and 5.1 (95% CI 2.6-7.5) months, respectively. Better OS was associated with serum AFP <400 (HR 0.27, p =0.02) in TARE&#95;alone, and IHT ≤50% (HR 0.39, p =0.004) and AFP <400 (HR 0.5, p =0.027) in TARE&#95;sorafenib. Unilobar involvement (HR 0.43, p =0.029) and AFP <400 ng/mL (HR 0.52, p =0.015) correlated with better PFS in TARE&#95;alone and TARE&#95;sorafenib, respectively. Adverse events (AEs) were more frequent in TARE&#95;sorafenib than TARE&#95;alone (92.4 vs 80.3%), but only 9.3% were grade 3 or higher AEs., Conclusion: TARE&#95;alone provided the most prominent survival benefit in IHT ≤50%-without ADF patients who had unilobar HCC and serum AFP <400 ng/mL. TARE and sorafenib yielded the best outcomes in patients with IHT ≤50% and serum AFP <400 ng/mL, with some additional grade 1-2 AEs compared to TARE only., Competing Interests: AM has received research grants from BTG International, Sirtex Medical, and ABK Medical and serves as a consultant for BTG, Sirtex, and Boston Scientific. JDK has received a research grant from Cynvenio Biosystems and is on a speaker bureau of Angiodynamics. He reports personal fees from BTG and Argon, and serves on an advisory board for Boston Scientific. BC serves on an advisory board for Advanced Accelerator Applications and Clovis Oncology. BCO. has received a research grant from Siemens Healthineers and serves as a consultant for Koo Foundation. SCK has received research grants from BTG International and GE Healthcare and serves as a consultant for BTG International, Terumo Medical, Sirtex Medical, and ABK Biomedical. The authors report no other conflicts of interest in this work., (© 2020 Teyateeti et al.)

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., (© Society of Breast Imaging 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Temporary balloon occlusion techniques have been described to redirect blood flow during hepatic chemo- and radioembolization. A 69 years old male with pathologically proven multifocal hepatocellular carcinoma involving all the liver segments except segments 2 and 3. We temporarily occlude segment 2/3 branch with the microvascular plug (MVP) to safely deliver the Y90 glass microspheres through the multiple small segment 4 branches. Distal occlusion using MVP may provide a valuable, cheaper and readily available tool in cases of unfavorable anatomy to divert blood flow and avoid non target delivery of Chemo or Radioembolic agents., (Published by Elsevier Inc. on behalf of University of Washington.)

Purpose: To report outcomes of yttrium-90 ( 90 Y) radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC)., Materials and Methods: Retrospective review was performed of 115 patients at 6 tertiary care centers; 92 were treated with resin microspheres (80%), 22 were treated with glass microspheres (19%), and 1 was treated with both. Postintervention outcomes were compared between groups with χ 2 tests. Survival after diagnosis and after treatment was assessed by Kaplan-Meier method., Results: Grade 3 laboratory toxicity was observed in 4 patients (4%); no difference in toxicity profile between resin and glass microspheres was observed (P = .350). Clinical toxicity per Society of Interventional Radiology criteria was noted in 29 patients (25%). Partial response per Response Evaluation Criteria In Solid Tumors 1.1 was noted in 25% of patients who underwent embolization with glass microspheres and 3% of patients who were treated with resin microspheres (P = .008). Median overall survival (OS) from first diagnosis was 29 months (95% confidence interval [CI], 21-37 mo) for all patients, and 1-, 3-, and 5-year OS rates were 85%, 31%, and 8%, respectively. Median OS after treatment was 11 months (95% CI, 8-13 mo), and 1- and 3-year OS rates were 44% and 4%, respectively. These estimates were not significantly different between resin and glass microspheres (P = .730 and P = .475, respectively). Five patients were able to undergo curative-intent resection after 90 Y radioembolization (4%)., Conclusions: This study provides observational data of treatment outcomes after 90 Y radioembolization in patients with unresectable ICC., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: Current treatment planning for 90 Y radioembolization estimates lung mean dose (LMD) by measuring the lung shunt fraction (LSF) from 99m Tc-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 99m Tc-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 (LMD new ) 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 LSF new from liver and lung counts; (d) calculate LMD new using LSF new and the total lung mass from the diagnostic CT (M new ). LMD new , LSF new , and M new estimates were compared to standard model values (LMD clin , LSF clin , and 1 kg, respectively) in 52 consecutive patients with hepatocellular carcinoma who underwent radioembolization using 90 Y 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 M new was 839 g (range, 550-1178 g) for men and 731 g (range, 548-869 g) for women. The median LSF new was 0.02 (range, 0.01-0.11), while the median LMD new was 4.9 Gy (range, 0.3-25.5 Gy). M new , LSF new , and LMD new were significantly lower than M clin , LSF clin , and LMD clin , with respective relative mean (±SD) differences of -20% (±16%) for M new , -63% (±15%) for LSF new , and -53% (±23%) for LMD new . The estimated 1-sigma uncertainties in M new , LSF new , and LMD new were 9%, 10%, and 13%, respectively., Conclusions: We derived a method to calculate lung mass and LSF using routinely available diagnostic chest CT and 99m Tc-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 90 Y radioembolizations., (© 2019 American Association of Physicists in Medicine.)

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.

Purpose: 90 Y-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 90 Y-dosimetry techniques have been implemented to explore tumor dose-response on the basis of 3D 90 Y-activity distribution from PET imaging. Despite being a theranostic study, the optimization of quantitative 90 Y-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 90 Y-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 90 Y dosimetry., Methods: A modified NEMA IEC phantom was used to emulate clinically relevant 90 Y-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 90 Y dosimetry, quantified as image-based DVH, in 90 Y-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 90 Y-PET iterations and filtration for volumetric quantification of the 90 Y 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 90 Y 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., (© 2018 American Association of Physicists in Medicine.)

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.

Purpose: To investigate hepatocellular carcinoma tumor dose-response characteristics based on voxel-level absorbed doses (D) and biological effective doses (BED) using quantitative 90 Y-single-photon emission computed tomography (SPECT)/computed tomography (CT) after 90 Y-radioembilization with glass microspheres. We also investigated the relationship between normal liver D and toxicities., Methods and Materials: 90 Y-radioembolization activity distributions for 34 patients were based on quantitative 90 Y-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 90 Y-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 (D 50% ) 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 90 Y-radioembolization with glass microspheres showed Dmean of 160 Gy and BEDmean of 214 Gy for D 50% 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: 90 Y-microsphere selective internal radiation therapy ( 90 Y-SIRT or 90 Y-radioembolization) is used in the management of unresectable liver tumors. 90 Y-SIRT presents a unique situation where the total 90 Y activity inside the liver can be determined with high accuracy (> 95%). 90 Y 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 90 Y-SPECT self-calibration on the quantification of absorbed doses following 90 Y-SIRT., Methods: 90 Y bremsstrahlung SPECT/CT images of 31 patients with hepatocellular carcinoma, collected following 90 Y-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 90 Y-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 90 Y-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 90 Y-SIRT dosimetry. Absorbed dose quantification using 90 Y-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 90 Y-SIRT dosimetry between different clinical studies., (© 2017 American Association of Physicists in Medicine.)

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 90 Y-microsphere therapy to quantify 90 Y 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 90 Y 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 68 Ge 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 90 Y PET/CT liver scans, because of the higher counting efficiency of SS mode, which leads to better image quality and quantification precision., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

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 99m Tc 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 99m Tc-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 T=C1C2eμtF, where C are counts within the square ROI circumscribing each sphere on detectors 1 and 2, μ is the linear attenuation coefficient of water, t is detector separation, and the factor F accounts for background activity. Four unique F definitions-standard GM, background-subtraction GM, MIRD Primer 16 GM, and a novel "volumetric GM"-were investigated. Error in T was calculated as the percentage difference with respect to in-air. Quantitative accuracy using the different GM definitions was calculated as a function of SBR, depth, and sphere size. Sensitivity of quantitative accuracy to ROI size was investigated. We developed an MBI simulation to investigate the robustness of our corrections for various ellipsoidal tumor shapes and detector separations., Results: Scatter correction factor k varied slightly (0.80-0.95) over a compressed breast thickness range of 6-9 cm. Corrected energy spectra recovered general characteristics of scatter-free spectra. Quantitatively, photopeak counts were recovered to <10% compared to in-air conditions after scatter correction. After GM attenuation correction, mean errors (95% confidence interval, CI) for all 54 imaging scenarios were 149% (-154% to +455%), -14.0% (-38.4% to +10.4%), 16.8% (-14.7% to +48.2%), and 2.0% (-14.3 to +18.3%) for the standard GM, background-subtraction GM, MIRD 16 GM, and volumetric GM, respectively. Volumetric GM was less sensitive to SBR and sphere size, while all GM methods were insensitive to sphere depth. Simulation results showed that Volumetric GM method produced a mean error within 5% over all compressed breast thicknesses (3-14 cm), and that the use of an estimated radius for nonspherical tumors increases the 95% CI to at most ±23%, compared with ±16% for spherical tumors., Conclusion: Using DEW scatter- and our Volumetric GM attenuation-correction methodology yielded accurate estimates of tumor counts in MBI over various tumor sizes, shapes, depths, background uptake, and compressed breast thicknesses. Accurate tumor uptake can be converted to radiotracer uptake concentration, allowing three patient-specific metrics to be calculated for quantifying absolute uptake and relative uptake change for assessment of treatment response., (© 2017 American Association of Physicists in Medicine.)

Purpose: To quantify differences that exist between dosimetry models used for 90 Y selective internal radiation therapy (SIRT)., Methods and Materials: Retrospectively, 37 tumors were delineated on 19 post-therapy quantitative 90 Y single photon emission computed tomography/computed tomography scans. Using matched volumes of interest (VOIs), absorbed doses were reported using 3 dosimetry models: glass microsphere package insert standard model (SM), partition model (PM), and Monte Carlo (MC). Univariate linear regressions were performed to predict mean MC from SM and PM. Analysis was performed for 2 subsets: cases with a single tumor delineated (best case for PM), and cases with multiple tumors delineated (typical clinical scenario). Variability in PM from the ad hoc placement of a single spherical VOI to estimate the entire normal liver activity concentration for tumor (T) to nontumoral liver (NL) ratios (TNR) was investigated. We interpreted the slope of the resulting regression as bias and the 95% prediction interval (95%PI) as uncertainty. MC NL single represents MC absorbed doses to the NL for the single tumor patient subset; other combinations of calculations follow a similar naming convention., Results: SM was unable to predict MC T single or MC T multiple (p>.12, 95%PI >±177 Gy). However, SM single was able to predict (p<.012) MC NL single , albeit with large uncertainties; SM single and SM multiple yielded biases of 0.62 and 0.71, and 95%PI of ±40 and ± 32 Gy, respectively. PM T single and PM T multiple predicted (p<2E-6) MC T single and MC T multiple with biases of 0.52 and 0.54, and 95%PI of ±38 and ± 111 Gy, respectively. The TNR variability in PM T single increased the 95%PI for predicting MC T single (bias = 0.46 and 95%PI = ±103 Gy). The TNR variability in PM T multiple modified the bias when predicting MC T multiple (bias = 0.32 and 95%PI = ±110 Gy)., Conclusions: The SM is unable to predict mean MC tumor absorbed dose. The PM is statistically correlated with mean MC, but the resulting uncertainties in predicted MC are large. Large differences observed between dosimetry models for 90 Y SIRT warrant caution when interpreting published SIRT absorbed doses. To reduce uncertainty, we suggest the entire NL VOI be used for TNR estimates when using PM., Competing Interests: Notification: AM receives research support from BTG and Sirtex., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: To assess differences between four different voxel-based dosimetry methods (VBDM) for tumor, liver, and lung absorbed doses following (90)Y microsphere selective internal radiation therapy (SIRT) based on (90)Y bremsstrahlung SPECT/CT, a secondary objective was to estimate the sensitivity of liver and lung absorbed doses due to differences in organ segmentation near the liver-lung interface., Methods: Investigated VBDM were Monte Carlo (MC), soft-tissue kernel with density correction (SKD), soft-tissue kernel (SK), and local deposition (LD). Seventeen SIRT cases were analyzed. Mean absorbed doses ([Formula: see text]) were calculated for tumor, non-tumoral liver (NL), and right lung (RL). Simulations with various SPECT spatial resolutions (FHWMs) and multiple lung shunt fractions (LSs) estimated the accuracy of VBDM at the liver-lung interface. Sensitivity of patient RL and NL [Formula: see text] on segmentation near the interface was assessed by excluding portions near the interface., Results: SKD, SK, and LD were within 5 % of MC for tumor and NL [Formula: see text]. LD and SKD overestimated RL [Formula: see text] compared to MC on average by 17 and 20 %, respectively; SK underestimated RL [Formula: see text] on average by -60 %. Simulations (20 mm FWHM, 20 % LS) showed that SKD, LD, and MC were within 10 % of the truth deep (>39 mm) in the lung; SK significantly underestimated the absorbed dose deep in the lung by approximately -70 %. All VBDM were within 10 % of truth deep (>12 mm) in the liver. Excluding 1, 2, and 3 cm of RL near the interface changed the resulting RL [Formula: see text] by -22, -38, and -48 %, respectively, for all VBDM. An average change of -7 % in the NL [Formula: see text] was realized when excluding 3 cm of NL from the interface. [Formula: see text] was realized when excluding 3 cm of NL from the interface., Conclusions: SKD, SK, and LD are equivalent to MC for tumor and NL [Formula: see text]. SK underestimates RL [Formula: see text] relative to MC whereas LD and SKD overestimate. RL [Formula: see text] is strongly influenced by the liver-lung interface.

We characterized the energy response of personal dose equivalent (Hp(10) in mrem) and the contribution of backscatter to the readings of two electronic personal dosimeter (EPD) models with radionuclides commonly used in a nuclear medicine clinic. The EPD models characterized were the RADOS RAD-60R, and the SAIC PD-10i. The experimental setup and calculation of EPD energy response was based on ANSI/HPS N13.11-2009. Fifteen RAD-60R and 2 PD-10i units were irradiated using (99m)Tc, (131)I, and (18)F radionuclides with emission energies at 140 keV, 364 keV, and 511 keV, respectively. At each energy, the EPDs output in Hp(10) [mrem] were recorded with 15 inch thick PMMA to simulate backscatter form the torso. Simultaneous free-in-air exposure rate measurements were also performed using two Victoreen ionization survey meters to calculate the expected EPD Hp(10) values per ANSI/HPS N13.11-2009. The energy response was calculated by taking the ratio of the EPD Hp(10) readings with the expected Hp(10) readings and a two-tailed z-test was used to determine the significance of the ratio deviating away from unity. The contribution from backscatter was calculated by taking the ratio of the EPD Hp(10) readings with and without backscatter material. A paired, two-tailed t-test was used to determine the significance of change in EPD Hp(10) readings. The RAD-60R mean energy response at 140 keV was 0.85, and agreed to within 5% and 11% at 364 and 511 keV, respectively. The PD-10i mean energy response at 140 keV was 1.20, and agreed to within 5% at 364 and 511 keV, respectively. On average, in the presence of acrylic, RAD-60R values increased by 32%, 12%, and 14%, at 140, 364, and 511 keV, respectively; all increases were statistically significant. The PD-10i increased by 25%, 19%, and 10% at 140 keV, 364 keV, and 511 keV, respectively; however, only the 140 keV measurement was statistically significant. Although both EPD models performed within the manufacturers' specifications of ± 25% in the energy ranges used, they fell outside of our criteria of 10% at lower energies, suggesting the need to calculate energy-dependent correction factors, depending on the intended EPD use.

Objective: The purpose of this article is to quantitatively investigate the accuracy and performance of dual-energy CT (DECT) material density images and to calculate the areal bone mineral density (aBMD) for comparison with dual-energy x-ray absorptiometry (DEXA)., Materials and Methods: A rapid-kilovoltage-switching DECT scanner was used to create material density images of various two-material phantoms of known concentrations under different experimental conditions. They were subsequently also scanned by single-energy CT and DEXA. The total uncertainty and accuracy of the DECT concentration measurements was quantified by the root-mean-square (RMS) error, and linear regression was performed to evaluate measurement changes under varying scanning conditions. Alterations to accuracy with concentric (anthropomorphic) phantom geometry were explored. The sensitivity of DECT and DEXA to changes in material density was evaluated. Correlations between DEXA and DECT-derived aBMD values were assessed., Results: The RMS error of DECT concentration measurements in air ranged from 9% to 244% depending on the materials. Concentration measurements made off-isocenter or with a different DECT protocol were slightly lower (≈ 5%), whereas measurement in scattering conditions resulted in a reduction of 8-27%. In concentric phantoms, higher-attenuating material in the outer chamber increased measured values of the inner material for all methods. DECT was more sensitive than DEXA to changes in BMD at 2 mg/mL K2HPO4. Measurements of aBMD using DECT and DEXA were highly correlated (R(2) = 0.98)., Conclusion: DECT material density images were linear in response but prone to poor accuracy and biases. DECT-based aBMD could be used to monitor relative change in bone density.

Purpose: Evaluation of count rate performance (CRP) is an integral component of gamma camera quality assurance and system deadtime (τ) may be utilized for image correction in quantitative studies. This work characterizes the CRP of three modern gamma cameras and estimates τ using two established methods (decay and dual source) under a variety of experimental conditions., Methods: For the decay method, uncollimated detectors were exposed to a Tc-99m source of relatively high activity and count rates were sampled regularly over 48 h. Input count rate at each time point was based on the lowest observed count rate data point. The input count rate was plotted against the observed count rate and fit via least-squares to the paralyzable detector model (PDM) to estimate τ (rates method). A novel expression for observed counts as a function of measurement time interval was derived, taking into account the PDM and the presence of background but making no assumption regarding input count rate. The observed counts were fit via least-squares to this novel expression to estimate τ (counts method). Correlation and Bland-Altman analyses were performed to assess agreement in estimates of τ between the rates and counts methods. The dependence of τ on energy window definition and incident energy spectrum were characterized. The dual source method was also used to estimate τ and its agreement with estimates from the decay method under identical conditions was also investigated. The dependences of τ on the total activity and the ratio of source activities were characterized., Results: The observed CRP curves for each gamma camera agreed with the PDM at low count rates but deviated substantially from it at high count rates. The estimates of τ determined from the paralyzable portion of the CPR curve using the rates method and the counts method were found to be highly correlated (r = 0.999) but with a small (~6%) difference. No statistically significant difference was observed between the estimates of τ using the decay or dual source methods under identical experimental conditions (p = 0.13). Estimates of τ increased as a power-law function with decreasing ratio of counts in the photopeak to the total counts. Also, estimates of τ increased linearly as spectral effective energy decreased. No significant difference was observed between the dependences of τ on energy window definition or incident spectrum between the decay and dual source methods. Estimates of τ using the dual source method varied as a quadratic on the ratio of the single source to combined source activities and linearly with total activity., Conclusions: The CRP curves for three modern gamma camera models have been characterized, demonstrating unexpected behavior that necessitates the determination of both τ and maximum count rate to fully characterize the CRP curve. τ was estimated under a variety of experimental conditions, based on which guidelines for the performance of CRP testing in a clinical setting have been proposed.

Purpose: To evaluate and characterize the performance of a new commercially available pixelated portable gamma camera Ergo (Digirad, Poway, CA)., Methods: The authors evaluated a pixelated portable gamma camera system, Ergo, that consists of 11 520 elements of 3 × 3 mm(2) CsI(Tl) crystals that are 6-mm thick and are coupled to silicon photodiodes. The detector element has a size of 3.31 × 3.24 mm(2). The gamma camera performance was evaluated for both low-energy all-purpose (LEAP) and low-energy high-resolution (LEHR) collimators. The flood-field uniformity for (99m)Tc and (201)Tl was assessed using fillable uniform flood phantoms. Energy spectra were acquired for (99m)Tc, (111)In, (201)Tl, and (67)Ga to evaluate energy linearity and energy resolution. Spectral fits were performed to calculate the photopeak energies and resolutions. The pixel size and multiwindow spatial registration (MWSR) was evaluated by measuring mixed (99m)Tc and (201)Tl point sources placed at known distances apart. The system's sensitivity was measured according to the National Electrical Manufacturer's Association (NEMA) NU1-2007 standards for both LEAP and LEHR collimators as a function of distance from the collimator surface (5, 10, 15, 20, 25, 30, and 40 cm). The system resolution without scatter was measured for both LEAP and LEHR using (99m)Tc-filled capillary tubes located at 0, 2, 4, 6, 10, and 12 cm away from the surface of the collimator. As a measure of the spatial resolution, the full width at half maximum (FWHM) at a given distance was calculated from the presampling line spread function (LSF), constructed from the line profiles of the capillary tubes at the same distance. As a comparison, the FWHM at 10 cm away from LEHR and LEAP collimators was also calculated from linear interpolation as described by NEMA NU-1 2007 and from fitting the profiles to a Gaussian-plus-constant model., Results: All isotope-collimator pairs demonstrated good flood-field uniformity with an integral uniformity of ≤5% and a differential uniformity of ≤3%. The system demonstrated excellent energy linearity with maximum discrepancy of measured keV from true keV of <1%. The energy resolution of the (99m)Tc 140-keV photopeak was 7.4%. The image pixel size was measured as 3.23 × 3.18 mm(2), and the MWSR was within 0.3 mm (or ~10% of the nominal pixel size). The system sensitivity at 10 cm was 112.6 cps/MBq (249.9 cpm/μCi) for LEAP and 63.1 cps/MBq (140.1 cpm/μCi) for LEHR. The system spatial resolution varied linearly with distance from the collimator and the FWHM were measured to be 7.2 and 8.9 mm at 10 cm for LEHR and LEAP, respectively., Conclusions: Herein, the authors describe detailed performance evaluation procedures of a new pixelated portable gamma camera system, which can also be applied to evaluate other pixelated gamma camera system. Spatial resolution assessment in near-field imaging condition offers a unique challenge where the measured FWHM is highly dependent on relative position between the capillary tube and the detector element. The evaluations of the Ergo gamma camera suggest suitable clinical imaging performance. This portable gamma camera has a high (LEAP) planar sensitivity, high energy and spatial resolutions that are comparable to other available gamma cameras, and it exhibits superior count rate performance that is linear up to tens of millions count per second. The Ergo imaging performance, however, can still be improved, for example, by optimizing collimator design for near field imaging., (© 2012 American Association of Physicists in Medicine.)