Lung Shunt Research Articles

Addressing lung truncation in 99mTc-MAA SPECT/CT for 90Y microsphere radioembolization treatment planning

BackgroundPrior studies have established that macroaggregated albumin (MAA)-SPECT/CT offers more robust lung shunt fraction (LSF) and lung mean absorbed dose (LMD) estimates in 90Y radioembolization in comparison to planar imaging. However, incomplete SPECT/CT coverage of the lungs is common due to clinical workflows, complicating its potential use for LSF and LMD calculations. In this work, lung truncation in MAA-SPECT/CT was addressed via correction strategies to improve 90Y treatment planning.MethodsLung truncation was simulated in 56 cases with adequate (> 90%, mean: 98%) lung coverage in MAA-SPECT/CT by removing slices in ~ 5 mm increments from the lung apices to the diaphragm. A wide range of lung coverages from 100% to < 1% in ~ 2% increments were created. LSF and LMD were calculated with four methods. (1) 2D planar imaging standard (not truncated), truncated lung SPECT/CT data was: (2) used with no corrections (SPECTTrunc), (3) uniformly extrapolated to full lung coverage (SPECTUniform), (4) fit with an empirical model to predict lung counts at full lung coverage (SPECTFit). To determine counts for LSF, full lung volumes, those modified at the lung/liver boundary (Lungs 2-cm), and those isolated to the left lung (Left Lung) were used. The correction methods were then applied to 31 independent cases without full lung coverage (< 90%, mean: 74%). The variations in LSF and LMD estimates from each correction method were analyzed.ResultsAveraged across simulated lung coverages from 40 to 80%, percent errors relative to non-truncated data for SPECTTrunc were (mean ± σ) − 22% ± 15% for LSF and 34% ± 29% for LMD. SPECTUniform had similar errors with 29% ± 26% for both LSF and LMD. SPECTFit yielded the most accurate and precise estimates for LSF and LMD, with errors of 11% ± 20% for both. The Left Lung approach equalized LMD errors in all three correction methods, with percent errors of 3% ± 17% (SPECTTrunc), 2% ± 17% (SPECTUniform), and 4% ± 13% (SPECTFit). In the 31 cases without ground truth LSF or LMD, Left Lung produced highly comparable LMD estimates, with a mean (max) coefficient of variation across the three correction methods of 4% (20%).ConclusionLSF and LMD can be estimated for 90Y radioembolization using truncated lung coverage data in MAA-SPECT/CT. Empirical models to predict lung counts at full lung coverage produced LSF and LMD estimates with minimal bias and uncertainty. With lung/liver boundary adjustments, all SPECT/CT methods assessed in this work yielded LMD estimates comparable to ground truth, even down to 50% lung coverage.

99mTc/90Y radiolabeled biodegradable gel microspheres for lung shutting fraction assessment and radioembolization in hepatocellular carcinoma theranostics

Transarterial radioembolization (TARE) is a well-established clinical therapy for the treatment of patients with intermediate to advanced hepatocellular carcinoma (HCC) or those who are ineligible for radical treatment. However, commercialized radioactive microspheres still have some issues, such as high density, complicated preparation, non-biodegradability. Furthermore, the use of different radioactive microspheres during TARE and lung shunt fraction assessment has led to inconsistencies in biodistribution in certain cases. This study employed biodegradable hyaluronic acid (HA) as the backbone and modified with bisphosphonate and methacrylic acid to prepare biodegradable gel microspheres (HAMS) using the water-in-oil emulsification and photo-crosslinking for labeling the diagnostic radionuclide of 99mTc and therapeutic radionuclide of 90Y. Both 99mTc radiolabeled HAMS (99mTc-HAMS) and radiolabeled 90Y-HAMS (90Y-HAMS) were highly efficient in radiolabeling and exhibited excellent radiostability in vitro and in vivo. 99mTc-HAMS are highly effective in assessing the LSF, while 90Y-HAMS, administered though TARE, are effective in inhibiting the growth of in situ HCC without any side effects. Both 99mTc-HAMS and 90Y-HAMS have promising clinical applications in HCC theranostics.

Streamlining Radioembolization without Lung Shunt Estimation versus Regular Radioembolization in Patients with Hepatocellular Carcinoma within the Milan Criteria

PurposeTo assess the effectiveness and safety of streamlining transarterial radioembolization (S-TARE) without lung shunt fraction estimation using nuclear medicine imaging, compared with regular transarterial radioembolization (R-TARE), for patients with hepatocellular carcinoma (HCC) within the Milan criteria. Materials and MethodsBetween January 2012 and December 2022, 100 consecutive patients with HCC within the Milan criteria underwent R-TARE (n = 38) or S-TARE (n = 62) and were retrospectively analyzed. Adverse events, complete response (CR) rates, and time to progression (TTP) by the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and localized mRECIST following each treatment were compared using the Fisher exact test and Kaplan-Meier curve analyses with covariate adjustment. ResultsSerious adverse events ≥ Grade 3 occurred in 3 (7.9%, 3/38) and 2 (3.2%, 2/62) patients following R-TARE and S-TARE, respectively (P = .365). No patients developed radiation pneumonitis. Among the 84 patients treated with glass microspheres, the CR rates were not significantly different after R-TARE (96.9%, 31/32) and S-TARE (90.4%, 47/52) (P = .400). There was no significant difference in TTP by mRECIST between R-TARE and S-TARE (unadjusted P = .400, adjusted P = .712). For patients with a single HCC, no significant difference was observed in TTP by localized mRECIST (unadjusted P = .090, adjusted P = .242). In the 16 patients treated with resin microspheres, the CR rates were 66.7% (4/6) for R-TARE and 90% (9/10) for S-TARE, respectively (P = .518). ConclusionsS-TARE using yttrium-90 glass or resin microspheres was as effective and safe as R-TARE for HCC within the Milan criteria.

Hepatopulmonary Shunt Ratio Verification Model for Transarterial Radioembolization.

The most important toxicity of transarterial radioembolization therapy applied in liver malignancies is radiation pneumonitis and fibrosis due to hepatopulmonary shunt of Yttrium-90 (90Y) microspheres. Currently, Technetium-99m macroaggregated albumin (99mTc-MAA) scintigraphic images are used to estimate lung shunt fraction (LSF) before treatment. The aim of this study was to create a phantom to calculate exact LFS rates according to 99mTc activities in the phantom and to compare these rates with LSF values calculated from scintigraphic images. A 3D-printed lung and liver phantom containing two liver tumors was developed from Polylactic Acid (PLA) material, which is similar to the normal-sized human body in terms of texture and density. Actual %LSFs were calculated by filling phantoms and tumors with 99mTc radionuclide. After the phantoms were placed in the water tank made of plexiglass material, planar, SPECT, and SPECT/CT images were obtained. The actual LSF ratio calculated from the activity amounts filled into the phantom was used for the verification of the quantification of scintigraphic images and the results obtained by the Simplicity90YTM method. In our experimental model, LSFs calculated from 99mTc activities filled into the lungs, normal liver, small tumor, and large tumor were found to be 0%, 6.2%, 10.8%, and 16.9%. According to these actual LSF values, LSF values were calculated from planar, SPECT/CT (without attenuation correction), and SPECT/CT (with both attenuation and scatter correction) scintigraphic images of the phantom. In each scintigraphy, doses were calculated for lung, small tumor, large tumor, normal liver, and Simplicity90YTM. The doses calculated from planar and SPECT/CT (NoAC+NoSC) images were found to be higher than the actual doses. The doses calculated from SPECT/CT (with AC+with SC) images and Simplicity90YTM were found to be closer to the real dose values. LSF is critical in dosimetry calculations of 90Y microsphere therapy. The newly introduced hepatopulmonary shunt phantom in this study is suitable for LSF verification for all models/brands of SPECT and SPECT/CT devices.

Effects of different VV ECMO blood flow rates on lung perfusion assessment by hypertonic saline bolus-based electrical impedance tomography

ObjectiveOur study aimed to investigate the effects of different extracorporeal membrane oxygenation (ECMO) blood flow rates on lung perfusion assessment using the saline bolus-based electrical impedance tomography (EIT) technique in patients on veno-venous (VV) ECMO.MethodsIn this single-centered prospective physiological study, patients on VV ECMO who met the ECMO weaning criteria were assessed for lung perfusion using saline bolus-based EIT at various ECMO blood flow rates (gradually decreased from 4.5 L/min to 3.5 L/min, 2.5 L/min, 1.5 L/min, and finally to 0 L/min). Lung perfusion distribution, dead space, shunt, ventilation/perfusion matching, and recirculation fraction at different flow rates were compared.ResultsFifteen patients were included. As the ECMO blood flow rate decreased from 4.5 L/min to 0 L/min, the recirculation fraction decreased significantly. The main EIT-based findings were as follows. (1) Median lung perfusion significantly increased in region-of-interest (ROI) 2 and the ventral region [38.21 (34.93–42.16)% to 41.29 (35.32–43.75)%, p = 0.003, and 48.86 (45.53–58.96)% to 54.12 (45.07–61.16)%, p = 0.037, respectively], whereas it significantly decreased in ROI 4 and the dorsal region [7.87 (5.42–9.78)% to 6.08 (5.27–9.34)%, p = 0.049, and 51.14 (41.04–54.47)% to 45.88 (38.84–54.93)%, p = 0.037, respectively]. (2) Dead space significantly decreased, and ventilation/perfusion matching significantly increased in both the ventral and global regions. (3) No significant variations were observed in regional and global shunt.ConclusionsDuring VV ECMO, the ECMO blood flow rate, closely linked to recirculation fraction, could affect the accuracy of lung perfusion assessment using hypertonic saline bolus-based EIT.

Radioembolization of HCC and secondary hepatic tumors: a comprehensive review.

Transarterial radioembolization (TARE), also called Selective Internal Radiation Therapy (SIRT), has emerged as an effective locoregional therapy for primary and secondary hepatic tumors, utilizing yttrium-90 (Y90) microspheres and other agents such as holmium-166 and rhenium-188. TARE has various applications in the management of HCC across different BCLC stages. Radiation segmentectomy, which involves administering high doses of Y90 (>190 Gy), can be both curative and ablative, achieving complete necrosis of the tumor. In contrast, radiation lobectomy involves administering a lower dose of Y90 (80-120 Gy) as a neoadjuvant treatment modality to improve local control and induce future liver remnant (FLR) hypertrophy in patients who are planned to undergo surgery but have insufficient FLR. Modified radiation lobectomy combines both techniques and offers several advantages over portal vein embolization (PVE). Y90 is also used in downstaging HCC patients outside liver transplantation criteria, as well as bridging those awaiting liver transplantation (LT). Multiple studies and combined analyses were described to highlight the outcomes of TARE and compare it with other treatment modalities, including TACE and sorafenib. Additionally, the review delves into the efficacy and safety of radioembolization in managing metastatic colorectal cancer and other metastatic tumors to the liver. Recent studies have emphasized the role of personalized dosimetry for improved outcomes, and thus we described the different methods used for this purpose. Pretherapy imaging, estimating lung shunt, selection of therapeutic radionuclides, adverse effects, and cost-effectiveness were all discussed as well.

Single-Session Ablative Transarterial Radioembolization for Patients with Hepatocellular Carcinoma to Streamline Care: An Initial Experience.

Transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) is performed after a mapping angiogram involving infusion of radiolabeled macroaggregated albumin to assess for non-target embolization and pulmonary shunting. The purpose of this case series was to evaluate the safety and feasibility of single-session TARE without the initial procedure. A single-institution case series of 16 consecutive procedures on 15 patients with 18 tumors who underwent an attempted single-session TARE procedures with glass microspheres are presented. A lung shunt fraction (LSF) of 5% was assumed for planning purposes. Sixty-seven percent (10/15) of patients were male with a median age of 72years. Median tumor size was 2.5cm (IQR 2.0-3.2cm). Sixteen of the 18 targeted tumors were untreated prior to the single-session TARE. Rate of technical success was 88% (14/16). Two patients did not ultimately receive a single-session TARE due to intraprocedural findings. The mean administered activity was 2.0GBq, and the mean MIRD dose was 464Gy based on pre-treatment anatomic imaging and 800Gy based on cone-beam CT. There were no cases of radiation pneumonitis. Mean post-procedural calculated lung dose was 4.9Gy (range 3.1-9.3) based on SPECT. An initial experience with single-session TARE using Y-90 glass microspheres without pre-procedural mapping angiography and lung shunt estimation demonstrates that it is a feasible and safe treatment option for select patients with small (< 5cm) HCC. Level 4 case series.

Beta-blockade for the treatment of refractory hypoxaemia during venovenous extracorporeal membrane oxygenation: An in-silico study.

Venovenous extracorporeal membrane oxygenation (VV ECMO) is used for refractory hypoxemia, although despite this, in high cardiac output states, hypoxaemia may persist. The administration of beta-blockers has been suggested as an approach in this scenario, however the physiological consequences of this intervention are not clear. We performed an in-silico study using a previously described mathematical model to evaluate the effect of beta-blockade on mixed venous and arterial saturations (, SaO2), in three different clinical scenarios and considered the potential effects of beta-blockers on, cardiac output, oxygen consumption and recirculation. Additionally we assessed the interaction of beta-blockade with haemoglobin concentration. In scenario 1: simulating a patient with high cardiac output and partial lung shunt decreased from increased 53.5% to 44.7% despite SaO2 rising from 74.2% to 79.2%. In scenario 2 simulating a patient with high cardiac output and complete lung shunt remained unchanged at 52.2% and SaO2 rose from 71.9% to 85%. In scenario 3 a patient with normal cardiac output and high recirculation fell from 50.8% to 25.5% and also fell from 82.4% to to 78.3%. Across the remaining modelling examples the effect on varied but oxygen delivery was consistently reduced across all scenarios. The administration of beta-blockers for refractory hypoxemia during VV ECMO are unpredictable and may reduce oxygen delivery, although this will vary with patient and circuit features. This study does not support the use of beta-blockers for this indication.

Establishing Updated Safety Standards for Independent 99mTc-MAA SPECT/CT Treatment Planning in Radioembolization

Significant improvements within radioembolization imaging and dosimetry permit the development of an accurate and personalized pretreatment plan using technetium 99m-labeled macroaggregated albumin (99mTc-MAA) and single-photon emission computed tomography (SPECT) combined with anatomical CT (SPECT/CT). Despite these potential advantages, the clinical transition to pretreatment protocols with SPECT/CT is hindered by their unknown safety constraints. This study aimed to address this issue by establishing novel dose limits for 99mTc-MAA SPECT/CT to enable quantitative pretreatment planning. Stratification criteria to determine images most viable for dosimetry analysis were created from a cohort of 85 patients. SPECT/CT, cone beam CT, and activity calculations derived from the local deposition method were used to create an accurate pretreatment protocol. Planar and SPECT/CT images were compared using linear regression and modified Bland-Altman analyses to convert accepted planar dose limits to SPECT/CT. To validate these new dose limits, activity calculations based on SPECT/CT were compared with those calculated with the body surface area and planar methods for three treatment plans. A total of 38 of 85 patients were deemed viable for dosimetry analysis. SPECT yielded greater lung shunt fractions (LSFs) than planar imaging when LSFs were <4.89%, whereas SPECT yielded lower LSFs than planar imaging when LSFs were >4.89%. Planar to SPECT/CT dose conversions were 0.76×, 0.70×, and 0.55× for the whole liver, normal liver, and lungs, respectively. Patients with SPECT LSFs ≤4.89% were safely treated with the direct application of planar lung dose limits. Activity calculations with the newly established SPECT/CT dose limits were greater than those of the body surface area method by a median range of 33.1% to 61.9% and were lower than planar-based activity calculations by a median range of 12.5% to 13.7% for the whole liver and by 29.4% to 32.2% for the normal liver. This study demonstrated a safe method for translating dose limits from 99mTc-MAA planar imaging to SPECT/CT. A robust pretreatment protocol was further developed guided by the current knowledge in the field. Established SPECT/CT dose limits safely treated 97.5% of patients and permitted the application of independent pretreatment planning with 99mTc-MAA SPECT/CT.

An international phantom study of inter-site variability in Technetium-99m image quantification: analyses from the TARGET radioembolization study

BackgroundPersonalised multi-compartment dosimetry based on [99mTc]Tc-MAA is a valuable tool for planning 90Y radioembolization treatments. The establishment and effective application of dose–effect relationships in yttrium-90 (90Y) radioembolization requires [99mTc]Tc-MAA SPECT quantification ideally independent of clinical site. The purpose of this multi-centre phantom study was to evaluate inter-site variability of [99mTc]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.ResultsRegarding 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).ConclusionEliminating 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.

Implications of lung shunt fraction calculation discrepancy in Y-90 radioembolization treatment from 2D planar vs 3D SPECT imaging

Abstract The safety and efficacy of Yttrium-90 (Y-90) radio-embolization therapy is partly dependent on the lung shunt fraction (LSF). There may be a notable disparity between LSF when calculated using 2D planar imaging vs 3D SPECT; this can affect the total allowable Y-90 dose delivered and therefore change the effectiveness of the procedure. The case presented demonstrates an 81% decrease in LSF when calculated by SPECT as compared to 2D planar imaging. This case highlights the importance of considering the imaging technique and the potential discrepancies that can arise between planar and SPECT imaging in LSF assessment.

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma.

This study showcases a comprehensive treatment protocol for high-risk hepatocellular carcinoma (HCC) patients, focusing on the combined use of Y-90 transarterial radioembolization (TARE) and Programmed Cell Death-1 (PD-1) inhibitors as neoadjuvant therapy. Highlighted through a case report, it offers a step-by-step reference for similar therapeutic interventions. A retrospective analysis was conducted on a patient who underwent hepatectomy following Y-90 TARE and PD-1 inhibitor treatment. Key demographic and clinical details were recorded at admission to guide therapy selection. Y-90 TARE suitability and dosage calculation were based on Technetium-99m (Tc-99m) macroaggregated albumin (MAA) perfusion mapping tests. Lesion coverage by Y-90 microspheres was confirmed through single photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging, and adverse reactions and follow-up outcomes were meticulously documented. The patient, with a 7.2 cm HCC in the right hepatic lobe (T1bN0M0, BCLC A, CNLC Ib) and an initial alpha-fetoprotein (AFP) level of 66,840 ng/mL, opted for Y-90 TARE due to high recurrence risk and initial surgery refusal. The therapy's parameters, including the lung shunting fraction (LSF) and non-tumor ratio (TNR), were within therapeutic limits. A total of 1.36 GBq Y-90 was administered. At 1 month post-therapy, the tumor shrank to 6 cm with partial necrosis, and AFP levels dropped to 21,155 ng/mL, remaining stable for 3 months. After 3 months, PD-1 inhibitor treatment led to further tumor reduction to 4 cm and AFP decrease to 1.84 ng/mL. The patient then underwent hepatectomy; histopathology confirmed complete tumor necrosis. At 12 months post-surgery, no tumor recurrence or metastasis was observed in follow-up sessions. This protocol demonstrates the effective combination of Y-90 TARE and PD-1 inhibitor as a bridging strategy to surgery for HCC patients at high recurrence risk, providing a practical guide for implementing this approach.

Effect of predicted lung mass versus fixed mass regimes on lung dose in SIRT (90Y)

This work sought to investigate the impact of fixed lung mass regime versus individualized measures on the lung absorbed dose in 90Y therapy. 14 patients were injected with 3-5 mCi 99mTc-MAA pursued by whole-body scans with 15% photo-peak window width at 140 keV. SPECT/CT scans were acquired with attenuation and scatter correction. The lung shunt fraction (LSF) was generated from whole-body scans (WBS) and SPECT/CT. Lung volume was measured by contouring the target organ over CT images. Variation, Kruskal Wallis, and Mann-Whitney tests were applied for statistical analysis. In result, 64% of the patients exhibited less than 1 kg lung mass, and the remaining 26% had lung mass larger than 1 kg. The estimated lung shunt fractions from SPECT/CT were greatly lower than planar images with a median of -45% (range: -28 to -69%). The lung dose estimates varied between fixed lung-mass regime used in (TheraSphere Treatment Sheet) and real measures approach with a median difference of 9% and a range from -34% to 76%. However, a significant difference was found in lung dose estimates between planar and SPECT/CT modalities independent of lung mass. It was accordingly inferred that lung mass may vary among patients influencing the predicted dose and the tailored 90Y activity. For precise medicine, the fixed lung mass used on a routine basis should be replaced by patient-specific measures.

PET/CT and SPECT/CT imaging of 90Y hepatic radioembolization at therapeutic and diagnostic activity levels: Anthropomorphic phantom study.

Prior to 90Y radioembolization procedure, a pretherapy simulation using 99mTc-MAA is performed. Alternatively, a small dosage of 90Y microspheres could be used. We aimed to assess the accuracy of lung shunt fraction (LSF) estimation in both high activity 90Y posttreatment and pretreatment scans with isotope activity of ~100 MBq, using different imaging techniques. Additionally, we assessed the feasibility of visualising hot and cold hepatic tumours in PET/CT and Bremsstrahlung SPECT/CT images. Anthropomorphic phantom including liver (with two spherical tumours) and lung inserts was filled with 90Y chloride to simulate an LSF of 9.8%. The total initial activity in the liver was 1451 MBq, including 19.4 MBq in the hot sphere. Nine measurement sessions including PET/CT, SPECT/CT, and planar images were acquired at activities in the whole phantom ranging from 1618 MBq down to 43 MBq. The visibility of the tumours was appraised based on independent observers' scores. Quantitatively, contrast-to-noise ratio (CNR) was calculated for both spheres in all images. LSF estimation. For high activity in the phantom, PET reconstructions slightly underestimated the LSF; absolute difference was <1.5pp (percent point). For activity <100 MBq, the LSF was overestimated. Both SPECT and planar scintigraphy overestimated the LSF for all activities. Lesion visibility. For SPECT/CT, the cold tumour proved too small to be discernible (CNR <0.5) regardless of the 90Y activity in the liver, while hot sphere was visible for activity >200 MBq (CNR>4). For PET/CT, the cold tumour was only visible with the highest 90Y activity (CNR>4), whereas the hot one was seen for activity >100 MBq (CNR>5). PET/CT may accurately estimate the LSF in a 90Y posttreatment procedure. However, at low activities of about 100 MBq it seems to provide unreliable estimations. PET imaging provided better visualisation of both hot and cold tumours.

The effects of scatter radiation and respiratory motion on Lung Shunt Fraction (LSF) quantification

The effects of scatter radiation and respiratory motion on Lung Shunt Fraction (LSF) quantification

Movement towards patient-specific scatter correction in Lung Shunt Fraction (LSF) quantification

Movement towards patient-specific scatter correction in Lung Shunt Fraction (LSF) quantification

The Role of Lung Density in the Voxel-Based Dosimetry of 90Y-TARE Evaluated with the Voxel S-Value (VSV) Method and Fast Monte Carlo Simulation

(1) Background: In 90Y-TARE treatments, lung-absorbed doses should be calculated according to the manufacturer’s instructions, using the MIRD-scheme. This scheme is derived from the assumption that 90Y-microspheres deliver the dose in a water-equivalent medium. Since the density of the lungs is quite different from that of the liver, the absorbed dose to the lungs could vary considerably, especially at the liver/lungs interface. The aim of this work is to compare the dosimetric results obtained by two dedicated software packages implementing a water-equivalent dose calculation and a Monte Carlo (MC) simulation, respectively. (2) Methods: An anthropomorphic IEC phantom and a retrospective selection of 24 patients with a diagnosis of HCC were taken into account. In the phantom study, starting from a 90Y-PET/CT acquisition, the liver cavity was manually fixed with a uniform activity concentration on PET series, while the lung compartment was manually expanded on a CT series to simulate a realistic situation in which the liver and lungs are adjacent. These steps were performed by using MIM 90Y SurePlan. Then, a first simulation was carried out with only the liver cavity filled, while a second one was carried out, in which the lung compartment was also manually fixed with a uniform activity concentration corresponding to 10% lung shunt fraction. MIM 90Y SurePlan was used to obtain Voxel S-Value (VSV) approach dose values; instead, Torch was used to obtain MC approach dose values for both the phantom and the patients. (3) Results: In the phantom study, the percentage mean dose differences (∆D%) between VSV and MC in the first and second simulation, respectively were found to be 1.2 and 0.5% (absolute dose variation, ∆D, of 0.7 and 0.3 Gy) for the liver, −56 and 70% (∆D of −0.3 and −16.2 Gy) for the lungs, and −48 and −60% (∆D of −4.3 and −16.5 Gy) for the Liver/Lungs Edge region. The patient study reports similar results with ∆D% between VSV and MC of 7.0%, 4.1% and 6.7% for the whole liver, healthy liver, and tumor, respectively, while the result was −61.2% for the left lung and −61.1% for both the right lung and lungs. (4) Conclusion: Both VSV and MC allowed accurate radiation dose estimation with small differences (&lt;7%) in regions of uniform water-equivalent density (i.e., within the liver). Larger differences between the two methods (&gt;50%) were observed for air-equivalent regions in the phantom simulation and the patient study.

Influence of Early Versus Delayed Hepatic Artery Perfusion Scan on 90Y Selective Internal Radiation Therapy Planning.

Purpose: This study evaluated the effect of an increase in the time interval between hepatic intra-arterial injection of 99mTc-macroaggregated albumin (MAA) and hepatic artery perfusion scintigraphy (HAPS) on the lung shunt fraction (LSF) and perfused volume (PV) calculations in the treatment planning of selective internal radiation therapy (SIRT). Methods: The authors enrolled 51 HAPS sessions from 40 patients diagnosed with primary or metastatic liver malignancy. All patients underwent scan at the first and fourth hour after hepatic arterial injection of 99mTc-MAA. Based on single-photon emission computed tomography images, LSF values were measured from each patient's first and fourth hour images. PV1 and PV4 were also calculated based on three-dimensional images using 5% and 10% cutoff threshold values and compared with each other. Results: The authors found that the median of LSF4 was statistically significantly higher than LSF1 (3.05 vs. 4.14, p ≤ 0.01). There was no statistically significant difference between PV1 and PV4 on the 10% (p = 0.72) thresholds. Conclusions: LSF values can be overestimated in case of delayed HAPS, potentially leading to treatment cancellation due to incorrectly high results in patients who could benefit from SIRT. Threshold-based PV values do not significantly change over time; nevertheless, keeping the short interval time would be safer.

Comparison of 3 Different Therapeutic Particles in Radioembolization of Locally Advanced Intrahepatic Cholangiocarcinoma.

Our objective was to compare 3 different therapeutic particles used for radioembolization in locally advanced intrahepatic cholangiocarcinoma. Methods: 90Y-glass, 90Y-resin, and 166Ho-labeled poly(l-lactic acid) microsphere prescribed activity was calculated as per manufacturer recommendations. Posttreatment quantitative 90Y PET/CT and quantitative 166Ho SPECT/CT were used to determine tumor-absorbed dose, whole-normal-liver-absorbed dose, treated-normal-liver-absorbed dose, tumor-to-nontumor ratio, lung-absorbed dose, and lung shunt fraction. Response was assessed using RECIST 1.1 and the [18F]FDG PET-based change in total lesion glycolysis. Hepatotoxicity was assessed using the radioembolization-induced liver disease classification. Results: Six 90Y-glass, 8 90Y-resin, and 7 166Ho microsphere patients were included for analysis. The mean administered activity was 2.6 GBq for 90Y-glass, 1.5 GBq for 90Y-resin, and 7.0 GBq for 166Ho microspheres. Tumor-absorbed dose and treated-normal-liver-absorbed dose were significantly higher for 90Y-glass than for 90Y-resin and 166Ho microspheres (mean tumor-absorbed dose, 197 Gy for 90Y-glass vs. 73 Gy for 90Y-resin and 50 Gy for 166Ho; mean treated-normal-liver-absorbed dose, 79 Gy for 90Y-glass vs. 37 Gy for 90Y-resin and 31 Gy for 166Ho). The whole-normal-liver-absorbed dose and tumor-to-nontumor ratio did not significantly differ between the particles. All patients had a lung-absorbed dose under 30 Gy and a lung shunt fraction under 20%. The 3 groups showed similar toxicity and response according to RECIST 1.1 and [18F]FDG PET-based total lesion glycolysis changes. Conclusion: The therapeutic particles used for radioembolization differed from each other and showed significant differences in absorbed dose, whereas toxicity and response were similar for all groups. This finding emphasizes the need for separate dose constraints and dose targets for each particle.

MIDOS: a novel stochastic model towards a treatment planning system for microsphere dosimetry in liver tumors.

Transarterial radioembolization (TARE) procedures treat liver tumors by injecting radioactive microspheres into the hepatic artery. Currently, there is a critical need to optimize TARE towards a personalized dosimetry approach. To this aim, we present a novel microsphere dosimetry (MIDOS) stochastic model to estimate the activity delivered to the tumor(s), normal liver, and lung. MIDOS incorporates adult male/female liver computational phantoms with the hepatic arterial, hepatic portal venous, and hepatic venous vascular trees. Tumors can be placed in both models at user discretion. The perfusion of microspheres follows cluster patterns, and a Markov chain approach was applied to microsphere navigation, with the terminal location of microspheres determined to be in either normal hepatic parenchyma, hepatic tumor, or lung. A tumor uptake model was implemented to determine if microspheres get lodged in the tumor, and a probability was included in determining the shunt of microspheres to the lung. A sensitivity analysis of the model parameters was performed, and radiation segmentectomy/lobectomy procedures were simulated over a wide range of activity perfused. Then, the impact of using different microspheres, i.e., SIR-Sphere®, TheraSphere®, and QuiremSphere®, on the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), and mean absorbed dose was analyzed. Highly vascularized tumors translated into increased TNR. Treatment results (TNR and LSF) were significantly more variable for microspheres with high particle load. In our scenarios with 1.5 GBq perfusion, TNR was maximum for TheraSphere® at calibration time in segmentectomy/lobar technique, for SIR-Sphere® at 1-3 days post-calibration, and regarding QuiremSphere® at 3 days post-calibration. This novel approach is a decisive step towards developing a personalized dosimetry framework for TARE. MIDOS assists in making clinical decisions in TARE treatment planning by assessing various delivery parameters and simulating different tumor uptakes. MIDOS offers evaluation of treatment outcomes, such as TNR and LSF, and quantitative scenario-specific decisions.