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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.)

Background: The endobronchial diagnosis of peripheral lung lesions suspected of lung cancer remains a challenge from a navigation as well as an adequate tissue sampling perspective. Cone-beam computed tomography (CBCT) guidance is a relatively new technology and allows for 3-dimensional imaging confirmation as well as navigation and biopsy guidance, but, also involves radiation. This study investigates how radiation exposure and diagnostic accuracy in the CBCT-guided navigation bronchoscopy evolves with increasing experience, and, with a specific tailoring of CBCT and fluoroscopic imaging protocols towards the procedure., Patients and Methods: In this observational clinical trial, all 238 consecutive patients undergoing a CBCT-guided navigation bronchoscopy from the start of our CBCT-guided navigation bronchoscopy program (December 2017) until June 2020 were included. Procedural dose characteristics and diagnostic accuracy are reported as a function of time., Results: Procedural radiation exposure as measured by the dose area product initially was 47.5 Gy·cm2 (effective dose: 14.3 mSv) and gradually reduced to 25.4 Gy·cm2 (5.8 mSv). The reduction in fluoroscopic dose area product was highest, from 19.0 Gy·cm2 (5.2 mSv) to 2.2 Gy·cm2 (0.37 mSv, 88% reduction), despite a significant increase of fluoroscopy time. The diagnostic accuracy of navigation bronchoscopy increased from 72% to 90%., Conclusion: A significant learning effect can be seen in the radiation safety and diagnostic accuracy of a CBCT-guided and augmented fluoroscopy-guided navigation bronchoscopy. With increasing experience and tailoring of imaging protocols to the procedure, the procedural accuracy improved, while the effective dose for patients and staff was reduced., Competing Interests: Disclosure: R.L.J.V. reports grants and nonfinancial support from Philips, personal fees and nonfinancial support from Medtronic, and in-kind support from Pentax Medical Europe, during the conduct of the study; grants from AstraZeneca Oncology, grants from the Ankie Hak Fund, grants from Siemens Healthineers outside the submitted work. W.v.d.S. and S.L. report being employed and therefore receiving financial compensation by Philips during and in the context of the study. E.H.F.M.v.d.H. reports grants from Philips, personal fees and nonfinancial support from Medtronic and Pentax Medical Europe, during the conduct of the study; grants from AstraZeneca Oncology, grants from the Ankie Hak Fund, grants from Pentax Medical Europe, and personal fees from Cook Medical, outside the submitted work. For the remaining authors there is no conflict of interest or other disclosures., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To evaluate the accuracy of cone-beam computed tomography (CT)-based augmented fluoroscopy (AF) image guidance for endobronchial navigation to peripheral lung targets., Methods: Prototypic endobronchial navigation AF software that superimposed segmented airways, targets, and pathways based on cone-beam CT onto fluoroscopy images was evaluated ex vivo in fixed swine lungs and in vivo in healthy swine (n = 4) without a bronchoscope. Ex vivo and in vivo (n = 3) phase 1 experiments used guide catheters and AF software version 1, whereas in vivo phase 2 (n = 1) experiments also used an endovascular steerable guiding sheath, upgraded AF software version 2, and lung-specific low-radiation-dose protocols. First-pass navigation success was defined as catheter delivery into a targeted airway segment solely using AF, with second-pass success defined as reaching the targeted segment by using updated AF image guidance based on confirmatory cone-beam CT. Secondary outcomes were navigation error, navigation time, radiation exposure, and preliminary safety., Results: First-pass success was 100% (10/10) ex vivo and 19/24 (79%) and 11/15 (73%) for in vivo phases 1 and 2, respectively. Phase 2 second-pass success was 4/4 (100%). Navigation errors were 2.2 ± 1.2 mm ex vivo and 4.9 ± 3.2 mm and 4.0 ± 2.6 mm for in vivo phases 1 and 2, respectively. No major device-related complications were observed in the in vivo experiments., Conclusions: Endobronchial navigation is feasible and accurate with cone-beam CT-based AF image guidance. AF can guide endobronchial navigation with endovascular catheters and steerable guiding sheaths to peripheral lung targets, potentially overcoming limitations associated with bronchoscopy., (Published by Elsevier Inc.)

Purpose: To determine the true distribution of radiopaque beads (ROBs) after hepatic embolization in swine as imaged by micro-computed tomography (microCT) compared with in vivo cone-beam computerized tomography (CT) imaged at different kVp settings., Materials and Methods: Swine (n = 3) underwent hepatic transarterial embolization (n = 6) with the use of 70-150-μm ROBs under fluoroscopic guidance. After stasis, in vivo cone-beam CT was performed at 120, 100, and 80 kVp. The animal was euthanized, the liver resected, and microCT with 17 μm resolution performed on embolized tissue samples. The resulting cone-beam CT and microCT data were segmented and registered. Total vessel length, minimum volume-enclosing ellipsoid (MVEE), and number of independent volumes were measured. Maximum-intensity projections (MIPs) were generated for each cone-beam CT., Results: Metrics for all cone-beam CT segmentations differed significantly from microCT segmentations. Segmentations at 80 kVp presented significantly greater vessel length, MVEE, and number of independent volumes compared with 100 kVp and 120 kVp. In addition, 100 kVp segmentations presented significantly greater vessel length than 120 kVp. MIPs presented greater visualization than cone-beam CT segmentations and improved as kVp decreased., Conclusions: The full ROB distribution was more extensive than was apparent on cone-beam CT. Quantitative measures of embolic distribution demonstrated significantly better correlation with microCT with decreasing kVp. Similarly, qualitative analysis of MIPs showed improved visualization of beads with decreasing kVp. These findings demonstrate the clinical value of 80 kVp and 100 kVp protocols in the imaging of radiopaque embolizations compared with 120 kVp. However, considerations on X-ray penetration and dose may favor use of 100 kVp imaging over 80 kVp., (Published by Elsevier Inc.)

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.)

Purpose: To describe clinical use and potential benefits of cone-beam computed tomography (CT) navigation to perform image-guided percutaneous tumor ablation., Materials and Methods: All ablations performed between February 2011 and February 2013 using cone-beam CT navigation were included. There were 16 patients who underwent 20 ablations for 29 lesions. Cone-beam CT ablation planning capabilities include multimodality image fusion and tumor segmentation for visualization, depiction of the predicted ablation zones for intraprocedural planning, and segmentation of the ablated area for immediate verification after treatment. Number and purpose of cone-beam CT scans were examined. The initial ablation plan, defined as number of probes and duration of energy delivery, was recorded for the 20 of the 29 lesions ablated. Technical success and local recurrences were recorded. Primary and secondary effectiveness rates were calculated., Results: Image fusion was used for 16 lesions, and intraprocedural ultrasound was used for 4 lesions. Of the 20 ablations, where the ablation plans were recorded, there was no deviation from the plan in 14 ablations. In the remaining 6 ablations, iterative planning was needed for complete tumor coverage. An average of 8.7 cone-beam CT scans ± 3.2 were performed per procedure, including 1.3 ± 0.5 for tumor segmentation and planning, 1.7 ± 0.7 for probe position confirmation, and 3.9 ± 2 to ensure complete coverage. Mean follow-up time was 18.6 months ± 6.5. Ablations for 28 of 29 lesions were technically successful (96.5%). Of ablations performed with curative intent, technical effectiveness at 1 month was 25 of 26 lesions (96.1%) and 22 of 26 lesions (84.6%) at last follow-up. Local tumor progression was observed in 11.5% (3 of 26 lesions)., Conclusions: Cone-beam CT navigation may add information to assist and improve ablation guidance and monitoring., (Published by Elsevier Inc.)