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Objectives: To evaluate anatomical and volumetric predictability of a cone beam computed tomography (CBCT)-based virtual parenchymal perfusion (VPP) software for the single-photon-emission computed tomography (SPECT)/CT imaging results during the work-up for transarterial radioembolization (TARE) procedure in patients with hepatocellular carcinoma (HCC)., Methods: VPP was evaluated retrospectively on CBCT data of patients treated by TARE for HCC. 99m Tc macroaggregated albumin particles ( 99m Tc-MAA) uptake territories on work-up SPECT/CT was used as ground truth for the evaluation. Semi-quantitative evaluation consisted of the ranking of visual consistency of the parenchymal enhancement and portal vein tumoral involvement on VPP and 99m Tc-MAA SPECT/CT, using a three-rank scale and two-rank scale, respectively. Inter-reader agreement was evaluated using a kappa coefficient. Quantitative evaluation included absolute volume error calculation and Pearson correlation between volumes enhanced territories on VPP and 99m Tc-MAA SPECT/CT., Results: Fifty-two CBCTs were performed in 33 included patients. Semi-quantitative evaluation showed a good concordance between actual 99m Tc-MAA uptake and the virtual enhanced territories in 73% and 75% of cases; a mild concordance in 12% and 10% and a poor concordance in 15%, for the two readers. Kappa coefficient was 0.86. Portal vein involvement evaluation showed a good concordance in 58.3% and 66.7% for the two readers, respectively, with a kappa coefficient of 0.82. Quantitative evaluation showed a volume error of 0.46 ± 0.78 mL [0.01-3.55], and Pearson R 2 factor at 0.75 with a p value < 0.01., Conclusion: CBCT-based VPP software is accurate and reliable to predict 99m Tc-MAA SPECT/CT anatomical and volumetric results in HCC patients during TARE., Key Points: • Virtual parenchymal perfusion (VPP) software is accurate and reliable in the prediction of 99m Tc-MAA SPECT volumetric and targeting results in HCC patients during transarterial radioembolization (TARE). • VPP software may be used per-operatively to optimize the microcatheter position for 90 Y infusion allowing precise tumor targeting while preserving non-tumoral parenchyma. • Post-operatively, VPP software may allow an accurate estimation of the perfused volume by each arterial branch and, thus, a precise 90 Y dosimetry for TARE procedures., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Objectives: The aims of this study were to develop a model to estimate drug dose delivered to tumors after transarterial chemoembolization (TACE) with radiopaque drug-eluting beads (DEBs) based on DEB density on cone-beam computed tomography (CT) and to evaluate drug penetration into tissue in a woodchuck hepatoma model., Materials and Methods: Transarterial chemoembolization was performed in woodchucks with hepatocellular carcinoma (N = 5) using DEBs (70-150 μm, LC Bead LUMI) loaded with doxorubicin. Livers were resected 45 minutes after embolization, immediately frozen, and cut using liver-specific, 3D-printed sectioning molds. Doxorubicin levels in tumor specimens were measured by high-performance liquid chromatography and correlated with DEB iodine content that was measured using prototype cone-beam CT-based embolization treatment planning software. Doxorubicin penetration into tissue surrounding DEBs was assessed by fluorescence microscopy of tumor sections. Fluorescence intensity was converted into doxorubicin concentration using calibration standards. Intensity-thresholded color heatmaps were generated representing extravascular drug penetration., Results: Consistent segmentation of DEBs on cone-beam CT was achieved using a semiautomated intensity thresholding method. A positive linear correlation (0.96) was found between DEB iodine content measured on cone-beam CT and the amount of doxorubicin measured in tumor specimens. Prediction of doxorubicin levels in tumor sections that were not included in model development was accurate, with a root-mean-square error of 0.08 mg of doxorubicin. Tumor penetration of eluted doxorubicin resulted in concentration gradients where drug content decreased with increasing distance from blood vessels containing DEBs. Drug penetration was greater for blood vessels containing DEB clusters compared with single DEB, with higher doxorubicin concentrations extending further away from the vessels., Conclusions: Estimation of drug dose delivered during transarterial chemoembolization in a woodchuck hepatocellular carcinoma model was possible using DEB radiopacity on cone-beam CT as a surrogate marker. Doxorubicin penetration was greatest adjacent to vessels containing DEB clusters compared with single DEB. Intraprocedural estimation of the spatial distribution of drug dose within the tumor could enable real-time adjustments to DEB delivery, to maximize treatment coverage or identify regions of tumor at risk for undertreatment., Competing Interests: Conflicts of interest and sources of funding: This work was supported by the Center for Interventional Oncology in the Intramural Research Program of the National Institutes of Health (NIH) by intramural NIH grants NIH Z01 1ZID BC011242 and CL040015. M.M.-H. is supported by the Clinical Translational Fellowship Program of the NIH Clinical Center and the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering. The NIH has a Materials Transfer Agreement with Northeastern Wildlife. The NIH has Cooperative Research and Development Agreements with Biocompatibles UK Ltd–Boston Scientific Corporation and Philips that provide support for this research. The NIH had control over the conduct of the study, the inclusion of any data, data analysis and interpretation, manuscript preparation, and decisions on submission for publication. The content of this manuscript does not necessarily reflect the views or policies of the US Department of Health and Human Services. The mention of commercial products, their source, or their use in connection with material reported herein is not to be construed as an actual or implied endorsement of such products by the US government. W.v.d.S. is an employee of Philips. A.L.L. was an employee of Biocompatibles UK Ltd, the company sponsoring the study. B.J.W. is the principal investigator for Cooperative Research & Development Agreements between NIH and the following: BTG Biocompatibles/Boston Scientific, Siemens, Philips, NVIDIA, Celsion Corp, Canon Medical, and XAct Robotics. B.J.W. and NIH are party to Material Transfer or Collaboration Agreements with Angiodynamics, 3T Technologies, Profound Medical, Exact Imaging, Johnson and Johnson, Endocare/Healthtronics, and Medtronic. Outside the submitted work, B.J.W. is primary inventor on 47 issued patents owned by the NIH (list available upon request), a portion of which have been licensed by NIH to Philips. B.J.W. and NIH report a licensing agreement with Canon Medical on algorithm software with no patent. B.J.W. is joint inventor (assigned to the Department of Health and Human Services NIH US government) for patents and pending patents related to drug-eluting bead technology, some of which have joint inventorships with BTG Biocompatibles/Boston Scientific. B.J.W. is primary inventor on patents owned by NIH in the space of drug-eluting embolic beads. The authors report no other conflicts of interest in this work. This manuscript discusses the use of an investigational device, software for iodine quantification in Emboguide, a Philips product., (Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Purpose: To evaluate accuracy of virtual parenchymal perfusion (VPP) algorithm developed for targeting liver cancer during intra-arterial therapy (IAT) using cone-beam CT guidance., Materials and Methods: VPP was retrospectively applied to 15 patients who underwent IAT for liver cancer. Virtual territory (VT) was estimated after positioning a virtual injection point on nonselective dual-phase (DP) cone-beam CT images acquired during hepatic arteriography at the same position chosen for selective treatment. Targeted territory (TT) was used as the gold standard and was defined by parenchymal phase enhancement of selective DP cone-beam CT performed before treatment start. Qualitative evaluation of anatomic conformity between VT and TT was performed using a 3-rank scale (poor, acceptable, excellent) by 3 double-blinded readers. VT and TT were also quantitatively compared using spatial overlap-based (Dice similarity coefficient [DSC], sensitivity, and positive predictive value), distance-based (mean surface distance [MSD]), and volume-based (absolute volume error and correlation between pairwise volumes) metrics. Interreader agreement was evaluated for the 2 evaluation methods., Results: Eighteen DP cone-beam CT scans were performed. Qualitative evaluation showed excellent overlap between VT and TT in 88.9%-94.4%, depending on the readers. DSC was 0.78 ± 0.1, sensitivity was 80%, positive predictive value was 83%, and MSD was 5.1 mm ± 2.4. Absolute volume error was 15%, and R 2 Pearson correlation factor was 0.99. Interreader agreement was good for both qualitative and quantitative evaluations., Conclusions: VPP algorithm is accurate and reliable in identification of liver arterial territories during IAT using cone-beam CT guidance., (Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.)