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A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time Intraprocedural Three-Dimensional Assessment of Ablative Treatments of Liver Malignancies

A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time Intraprocedural... Cardiovasc Intervent Radiol (2018) 41:1049–1057 https://doi.org/10.1007/s00270-018-1909-0 CLINICAL INVESTIGATION INTERVENTIONAL ONCOLOGY A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time Intraprocedural Three-Dimensional Assessment of Ablative Treatments of Liver Malignancies 1 1 2,3 1 • • • • Marco Solbiati Katia M. Passera S. Nahum Goldberg Alessandro Rotilio 4 4 4 4,5 • • • Tiziana Ierace Vittorio Pedicini Dario Poretti Luigi Solbiati Received: 1 August 2017 / Accepted: 17 February 2018 / Published online: 28 February 2018 The Author(s) 2018. This article is an open access publication Abstract Results Registration quality was high for both radiologists Aim To evaluate a novel contrast-enhanced cone-beam (R1: 4.3 ± 0.6, R2: 4.4 ± 0.5; p = 0.87). Comparisons computed tomography (CE-CBCT) registration method for between the registration of pre-ablation CECT with CE- accurate immediate assessment of ablation outcomes. CBCT versus post-ablation CECT regarding the position of Materials and Methods Contrast-enhanced computed the ablated area to the treated target (R1: 4.4 ± 0.6, R2: tomography (CECT) was registered with CE-CBCT by 4.6 ± 0.4) and treatment outcome (R1: 4.5 ± 0.5, R2: applying semiautomatic landmark registration followed by 4.6 ± 0.4) were equivalent (p[ 0.35). Increased confi- automatic affine and non-rigid registration to correct for dence was noted when using fusion (R1: 4.6 ± 0.4, R2: respiratory phase differences and liver deformation. This 4.6 ± 0.4; p = 0.84). Moreover, in 6 ablations (15.8%) the scheme was retrospectively applied to 30 patients who intraprocedural registered CBCT showed residual tumor underwent 38 percutaneous microwave liver ablations. precisely where identified on the 24 h post-ablation CECT. Three datasets were obtained for each case: (1) conven- Conclusions Combined CE-CBCT holds the potential to tional CECT scans 24 h before ablation, (2) intraprocedural change the current workflow of mini-invasive cancer local CE-CBCT scans, and (3) CECT scans 24 h post-ablation. treatments. Given earlier visual identification of residual Using a five-point scale, two experienced radiologists tumor post-ablation, this includes potentially eliminating qualitatively assessed registration quality, equivalence of the need for some additional treatments. CE-CBCT assessment of ablation outcome to 24 h post- ablation CECT, and perceived increase of confidence using Keywords Interventional radiology  Microwave the fusion method to CBCT alone. Additionally, residual Ablation  Liver tumors  Cone-beam CT post-ablation tumor volumes were measured at both CE- CBCT and 24 h CECT and compared to the pre-CECT. Introduction & Marco Solbiati m.solbiati@endo-sight.it Image-guided ablation using radiofrequency or micro- R&D Unit, R.A.W. Srl, Busto Arsizio, VA, Italy waves (MWA) has gained widespread attention and broad Department of Radiology, Hadassah Hebrew University clinical acceptance as minimally invasive treatment of liver Medical Centre, Jerusalem, Israel malignancies, particularly in non-surgical candidates [1–4]. Department of Radiology, Beth Israel Deaconess Medical Their success, however, relies strongly upon the operator’s Center, Boston, MA, USA skill and experience. Indeed, good clinical outcomes are Department of Radiology, Humanitas Clinical and Research predicated upon accurate selection criteria (i.e., tumor size, Center, Rozzano, Milan, Italy number, location, distance from major blood vessels), Department of Biomedical Sciences, Humanitas University, precise placement of ablative device(s), selection of Rozzano, Milan, Italy 123 1050 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… optimal ablation parameters, and a thorough and accurate Materials and Methods assessment of the completeness of treatment post-ablation. Lack of local tumor progression can only be confidently Pre-ablation Registration of CECT with CE-CBCT inferred when the ablation zone extends 5–10 mm beyond the entire tumor [5–7]. Real-time assessment could enable Registration of CECT with CE-CBCT consists of four immediate further treatment when this desired periabla- steps: (1) pre-ablation CECT re-sampling at CBCT reso- tional margin is not achieved, potentially avoiding subse- lution, (2) semiautomatic rigid registration, (3) automatic quent additional treatment sessions. affine registration followed by nonlinear registration, and Currently, many liver tumor ablations are performed (4) overlapping of pre-ablation CECT segmented over the using ultrasonography, where despite combined use of registered target on CE-CBCT. contrast-enhanced sonography and fusion imaging, imme- The semiautomatic rigid registration is based upon diate assessment of ablative margins can be hampered by selection of three corresponding landmarks visible in both incomplete three-dimensional evaluation [8, 9]. Likewise, image datasets. Here, intrahepatic blood vessels were when using CT guidance, the ablation margin is most often selected as these are closer to the target and have less risk assessed subjectively—comparing pre-ablation contrast- of deformity from respiratory motion than the outer con- enhanced CT (CECT) or MRI with post-ablation CECT. tour of the liver [16]. This step is necessary as CBCT and This is often accomplished solely by manually measuring CT images often do not completely overlap and automatic distances from the tumor edge or ablation zone to selected registration cannot correct this large mismatch. To correct landmarks in both studies. This is time-consuming and for different liver shapes, different breathing phases and does not allow precise, quantitative three-dimensional motion artifacts, subsequent affine and nonlinear registra- assessment of ablative margins, given the subjective spatial tions are automatically performed. For this procedure, CE- co-registration of pre-ablation tumor volume with post- CBCT is considered the fixed (i.e., template) imaging ablation necrosis. In order to overcome such limitations, modality with CECT the moving (i.e., superimposed) software for three-dimensional co-registration has recently image. To accomplish this, the CECT is warped upon the become available, but has yet to make a widespread impact CE-CBCT in order to achieve registration. The method is on this clinical need [10]. implemented using Insight Toolkit (ITK) libraries and Nowadays, contrast-enhanced cone-beam CT (CE- Elastix toolbox [17, 18]. Normalized mutual information CBCT) is increasingly used in local treatments of liver was used for registration as it offers the best performance malignancies, including both transcatheter chemoem- in cases of multimodality. Nonlinear registration is based bolization and percutaneous ablation. Despite poorer res- on B splines [17]. olution, CE-CBCT provides fast generation of volumetric images with lower radiation dose compared to conven- Protocol tional CT, enabling the interventionalist to plan and directly guide procedures based upon immediate assess- Our CECT-CE-CBCT co-registration algorithm was ret- ment of results achieved [11–15]. Yet, comparison of post- rospectively applied to 30 patients (22 males and 8 ablation CBCT with pre-ablation CECT scans is very females, aged 65–85 years) who underwent 38 percuta- cumbersome as CT and CBCT datasets differ with respect neous microwave liver ablations (MWA) (28 hepatocellu- to many parameters, and software providing fast and lar carcinomas (HCCs) in 22 patients and 10 cases of accurate three-dimensional co-registration of CECT and colorectal metastases (MET) in 8 patients). Tumor diam- CE-CBCT is currently not available. eters ranged from 0.7 to 3.3 cm (0.38–14.49 cc volume) To surmount this issue, we introduce here a novel (Table 1). One patient underwent two treatments, since in method that combines state-of-the-art image processing the first session one tumor was not fully ablated. algorithms to provide precise and fast spatial co-registra- For each case, three datasets were obtained: (1) con- tion of pre-treatment CECT with immediate post-treatment ventional CECT scans 24 h before ablation, (2) intrapro- CE-CBCT, to enable accurate assessment of ablative cedural CE-CBCT scans, and (3) CECT scans 24 h after margins in three dimensions immediately post-ablation. ablation. Pre- and post-ablation CT examinations were performed using a 64-slice scanner (GE Healthcare, Milwaukee, USA) after intravenous administration of 120–140 cc (mean, 129 ± 8) non-ionic contrast medium (iomeprol, Iomeron 300; Bracco, Milan, Italy) at 3 cc/s. Automatic bolus tracking (20 ml at 3 cc/s) was used, with monitoring scans 123 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… 1051 Table 1 Patients and treatment data Treatment Patient (male/ Tumor Tumor location Tumor volume Post-CT ablation Residual tumor volume 3 3 3 female, age) type (segment) (cm ) volume (cm ) percentage (cm %) 1 M, 71 HCC 6 0.8 19.1 0 2 M, 81 HCC 8 2.1 47.1 0.03 (1.4%) HCC 2 0.5 5.0 0.5 (100%) 3 M, 70 HCC 4 3.2 43.7 0.2 (6.3%) 4M,81 HCC 2 0.6 28.2 0.01 (1.2%) 5 F, 74 MET 7 11.2 39.2 0.2 (5.8%) 6 M, 75 HCC 2 13.6 18.2 0.6 (14.3%) 7 F, 80 HCC 4 0.9 3.0 0 8M,85 HCC 5 11.7 25.0 3.3 (28.3%) 9 M, 70 HCC 8 4.8 10.5 0 10 M, 71 HCC 5 1.1 5.3 0 11 M, 76 MET 8 0.5 2.9 0.01 (12.8%) 12 M, 82 HCC 6 0.5 3.3 0 13 M, 71 MET 4 1.0 5.2 0 14 M, 80 HCC 4 11.1 35.7 1.3 (11.5%) 15 F, 65 MET 2 1.0 15.4 0.6 (58.1%) 16 M, 79 HCC 8 1.5 9.7 0 HCC 2 2.5 9.3 0 17 M, 77 HCC 3 9.4 23.9 0 18 M, 70 HCC 5 1.4 2.9 0 HCC 4 5.0 10.0 0 19 F, 83 HCC 8 2.8 4.0 0 20 F, 76 HCC 8 0.6 3.7 0 HCC 4 0.8 5.3 0 21 M, 81 HCC 5 4.7 12.0 0 22 F, 72 HCC 6 5.7 7.6 0.6 (10.2%) 23 M, 81 HCC 2 6.9 13.0 1.7 (24.2%) 24 M, 72 HCC 4 14.5 20.9 0 HCC 3 0.8 4.0 0.8 (100%) 25 M, 82 MET 2 10.3 22.9 0 26 M, 81 HCC 2 0.4 18.8 0 27 F, 75 HCC 5 2.5 6.6 0 HCC 2 1.2 7.0 0.4 (31.7%) 28 M, 78 MET 7 0.8 3.8 0 MET 8 0.4 2.9 0 29 F, 78 MET 8 2.5 4.0 0 MET 2 1.1 5.3 0 30 M, 77 MET 2 0.6 3.0 0 Residual tumor volume means the volume of the portion of unablated tumor as a result of incomplete ablation The totally missed targets (italics) and the targets with a volume of unablated tumor ranging from 20 to 58.1% of the initial volume (bold) are highlighted Treatment 2 and Treatment 4 were performed in the same patient acquired starting after a delay of 8 s. Approximately 6–9 s venous phase scans automatically started 15 s after com- thereafter, the contrast enhancement threshold (90 HU) was pletion of the arterial phase scans. Both phases were per- reached within the ROI (i.e., the lumen of the descending formed with 3–5 mm collimation and 2–2.5 mm aorta), and arterial phase scans were acquired. Portal reconstruction intervals, with a matrix of 512 9 512 pixels, 123 1052 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… and in-plane pixel size of 0.48–0.86 mm (mean CT (1: [ 7 mm, 2: 5–7 mm, 3: 3–5 mm, 4: 1–3 mm, 5: 0.68 ± 0.07). \ 1 mm). Five to ten minutes following cessation of microwave Finally, evaluation of the radiologist’s perceived ablation, post-ablation CE-CBCT dataset volumes includ- improved confidence in achieving complete ablation over ing the entire patients’ livers were acquired at CBCT (Artis simple visualization of the CBCT image set without image zee, Siemens Healthcare, Erlangen, Germany) after intra- registration was performed using a 1–5-scale scoring sys- venous administration of 120 cc of iomeprol at 3 cc/s. tem (1: no confidence increase, 2: low 3: discrete/moderate Arterial and portal venous phase axial scans were triggered 4: high, and 5: very high). The results of all four gradings 3 and 30 s after the injection of contrast medium and by the radiologists were subject to inter-observer analysis, reconstructed perpendicular to the patient’s longitudinal including direct comparison using Student’s T test. axis. Scanning parameters were 1.2 m source detector distance, 1.5 rotation step, 5 s rotation duration, 200 total arc trajectory range, 128 images (projections), 0.36 Results microGy/frame radiation dose, and 2–5 mm reconstruction intervals. Each reconstructed CT slice had a 512 9 512 Whole liver imaging was possible in all patients, based pixels matrix, with an in-plane pixel size of 1.02–1.20 mm upon accurate pre-procedural patient centering. The aver- (mean 1.18 ± 0.3). Each 3D scan covered an approximate age time required to perform the entire procedure of volume of 250 9 200 9 200 mm. landmark selection and co-registration ranged from 30 to 120 s. An example of the registration achieved is shown in CT Image Preprocessing Fig. 1. The quantitative results of the clinical evaluation are For registration, the arterial phase scans were used as they summarized in Table 2. Overall, extremely high concor- provided the greatest enhancement of the tumors. dance was noted between both radiologists with identical Pre-ablation and post-ablation CECT images were fil- grades of 43.3, 37.4, 78.9, and 60.5% assigned for regis- tered with a diffusion filter in order to reduce noise [19] for tration quality, position, clinical indication, and confidence automatic segmentation of liver, tumor, and resultant improvement, respectively, and with no case noted of ablation zone. For liver segmentation, a fast marching and discordance by more than one category (Table 2). 3D geodesic active contour program identified and selected Registration quality was on average scored extremely the entire liver [20]. As a final preprocessing step that high for both radiologists (R1: 4.3 ± 0.6, R2: 4.4 ± 0.5, finalized the CECT segmentation, tumor and induced mean ± standard deviation; p = 0.87), with no grade 1 or coagulation necrosis were further segmented using a hybrid 2 observations recorded. Comparisons between the regis- of fuzzy c-means algorithm and random walkers method tration of pre-ablation CECT with CE-CBCT to pre-abla- based upon CT density [21]. tion CECT with post-ablation CECT for both position of the ablated area with the treated target (R1: 4.4 ± 0.6, R2: Clinical Evaluation 4.6 ± 0.4) and treatment outcome (R1: 4.5 ± 0.5, R2: 4.6 ± 0.4) were equivalent (p = 0.36 and 0.73, respec- Two radiologists, each with a history of more than 2000 tively). Finally, a demonstrably higher increase of confi- ablation procedures, performed, evaluated our method, dence was noted for both radiologists (R1: 4.6 ± 0.4, R2: based upon three criteria: registration quality, correspon- 4.6 ± 0.4; p = 0.84) when they could replace the simple dence of the assessments of ablation outcomes and per- visual inspection of CBCT images without any registration ceived increase of confidence for treatment evaluation. with the proposed method of spatial overlapping of CBCT Registration quality was assessed by visually comparing images with pre-ablation images. A full 75/78 of compar- images before and after the overlapping registration of pre- isons (96.1%) were rated as ‘‘high’’ or ‘‘very high’’ with no ablation CECT images over CE-CBCT images. Next, the grade 1 or 2 observations were noted by either radiologist radiologists evaluated the accuracy of post-ablation out- and only 3 of 78 observations (3.9%) rendered grade 3 as comes comparing pre-ablation CECT fused to intraproce- ‘‘discrete/moderate.’’ dural immediate CE-CBCT with that of 24 h post-ablation Moreover, with registration of pre-CECT with CE- CECT. Both registration quality and ablation outcomes CBCT the amount of residual post-ablation tumor volume assessments were performed according to a qualitative was measured. In 24/38 (63.2%) ablations, the registration five-point scale (1: poor—2: fair—3: satisfactory—4: did not show any residual tumor and for all 24/24 (100%) good—5: excellent). Spatial position accuracy was defined of them no residual tumor was also detected on the 24 h as displacement between the tumor location on the pre- post-ablation CECT (Fig. 2). In 12/38 (31.6%) ablations, ablation CT when overlapped to CBCT and post-ablation the intraprocedural registered CBCT showed residual 123 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… 1053 Fig. 1 Effects of image registration. Unregistered pre-CT (in purple substantial misalignment occurring before registration (manifest as a color) overlapped to CBCT (in green color) (first row) compared to purple shadow) was almost completely eliminated using our new registered pre-CT overlapped to CBCT (second row) for three fusion method despite the technical differences between the two representative slices of patient #1. The comparison shows that the different imaging modalities unablated tumor, ranging from 1.2 to 58.1% (mean Discussion 17.2 ± 16%) of the initial tumor volume. In 4/12 (33.3%) cases, the amount of unablated tumor ranged from 20 to We describe a novel registration method between post- 58.1% of the initial tumor volume and for all 4 of these the ablation CBCT and pre-ablation CECT scans that facili- 24 h post-ablation CECT showed a rim of residual tates intraprocedural treatment assessment. enhancement indicating incomplete ablation [22] (Fig. 3). Although CT and CBCT are both based upon radiation In the remaining 8/12 (66.7%) cases, the amount of and computed tomography, their datasets differ with unablated tumor detected by CBCT ranged from 1.2 to respect to many parameters including: the field-of-view 14.3% of the initial volume. In these 8 (100%), the 24 h focusing of interest, speed of rotation, susceptibility to post-ablation CECT did not detect any residual enhance- motion, different signal-to-noise ratios, image resolution ment. In the last 2/38 (5.3%) treatments, both intraproce- and CBCT scan artifacts that may lead to non-uniform dural registered CBCT and 24 h post-ablation CECT intensity images [23]. Additionally, liver parenchyma often showed that the target was completely missed (Fig. 4). undergoes significant deformation (particularly in cranial Thus, ultimately in 6/38 (15.8%) cases (4/38 (10.5%) segments) due to respiratory movement [24]. These issues with the amount of unablated tumor ranging from 20 to make co-registration of the two volume datasets non-intu- 58.1% and 2/38 (5.3%) with a completely missed target) itive and challenging. our CBCT fusion method identified the need for retreat- Prior studies addressing CBCT registration in different ment as confirmed by the post-ablation CECT. anatomic sites [25, 26], including liver [23, 27–29] have predominantly focused upon adaptive radiation therapy. Image fusion of pre-treatment CT with post-treatment CBCT for the assessment of ablation margins has been previously described, but has been performed through landmark rigid registration, which does not take into account modifications of liver and target tumor shape 123 1054 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… Table 2 Results of clinical evaluation Treatment Registration quality Tumor Target position (segment) Correspondence with post-CT Confidence improvement Position Clinical indication R1 R2 R1 R2 R1 R2 R1 R2 1 5 4 HCC 6 5 5 5 5 5 5 2 3 3 HCC 2 3 3 3 3 4 5 HCC 8 4 3 4 4 4 5 3 4 4 HCC 4 4 5 5 5 5 4 4 3 4 HCC 2 4 5 5 5 5 5 5 5 5 MET 7 4 5 4 5 5 5 6 5 5 HCC 2 5 5 5 5 5 5 7 4 5 HCC 4 5 4 5 5 5 5 8 5 4 HCC 5 4 5 4 5 5 4 9 5 5 HCC 8 5 5 5 5 5 5 10 4 5 HCC 5 5 4 5 5 5 5 11 5 4 MET 8 5 4 5 5 5 5 12 5 4 HCC 6 5 5 4 4 4 5 13 4 5 MET 4 4 5 5 5 5 4 14 2 3 HCC 4 4 4 4 4 4 3 15 3 3 MET 2 3 4 4 3 4 4 16 5 4 HCC 8 4 5 4 4 4 4 HCC 2 3 4 3 3 3 4 17 5 5 HCC 3 4 5 4 4 4 5 18 5 5 HCC 5 5 5 5 5 5 5 HCC 4 5 5 5 5 5 5 19 4 5 HCC 8 4 5 5 4 5 5 20 5 5 HCC 8 5 5 5 5 5 5 HCC 4 5 5 5 5 5 5 21 5 4 HCC 5 4 4 3 3 3 4 22 4 4 HCC 6 5 4 5 5 5 4 23 5 4 HCC 2 4 5 4 5 4 4 24 4 5 HCC 4 5 5 5 5 5 4 HCC 3 5 4 5 5 5 5 25 5 4 MET 2 5 5 5 5 5 4 26 3 4 HCC 2 5 4 5 4 5 5 27 5 5 HCC 5 4 5 4 5 4 5 HCC 2 4 5 4 5 4 5 28 5 5 MET 7 4 4 4 4 4 4 MET 8 5 4 5 5 5 5 29 5 5 MET 8 5 5 5 5 5 5 MET 2 5 5 5 5 5 5 30 4 5 MET 2 5 5 5 5 5 5 Average 4.3 4.4 4.4 4.6 4.5 4.6 4.6 4.6 Standard deviation 0.6 0.5 0.6 0.4 0.5 0.4 0.4 0.4 induced by patient breathing and/or movement—factors our algorithm surmounts these issues by providing auto- shown to impede ablation success [24, 30, 31]. However, matic rigid and non-rigid registration. 123 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… 1055 PRE-CT CBCT POST-CT Fig. 2 Demonstration of successful ablation treatment at CBCT. First 24-h post-ablation with CECT (post-CT) (with the pre-treatment HCC HCC of patient #2, studied with CECT before ablation (PRE-CT) colored in red). Both CBCT and post-CT show the ablated area (HCC indicated by yellow arrow), intraprocedural CBCT co-regis- entirely surrounding the target tered with PRE-CT (with the pre-treatment HCC colored in red) and POST-CT PRE-CT CBCT Fig. 3 Incomplete treatment detected by CBCT. Intraprocedural The medial portion (yellow arrows) of the HCC (colored in red) is not CBCT registered with PRE-CT in patient #8 of Table 1 shows partial entirely covered by the ablated area both on CBCT and on post-CT failure of the ablation treatment, as confirmed by the 24 h post-CT. Fig. 4 CBCT demonstration of PRE-CT POST-CT CBCT missed target. Comparison among pre-ablation CT (PRE- CT), intraprocedural registered CBCT, and 24 h post-ablation CT (post-CT) (second HCC of patient #2). After the first treatment, both CBCT and post- CT show that the HCC (colored in red and indicated by yellow arrows) is entirely located outside the volume of ablation (missed target) (top row). Most notably, the ablated area (indicated by the white arrows of the second row) is located caudally with respect to the actual target position (yellow arrows of the first row) both on CBCT and post-ablation CT. In the bottom row, the successful retreatment is shown, with the ablated area (yellow arrows) fully covering the target (red dot) 123 1056 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… S. Nahum Goldberg performs unrelated consulting for Angiody- Equivalent quality and confidence were noted for both namics and Cosman Instruments. types of fusion images by the two radiologists. Further- more, despite substantial clinical experience, confidence in Informed Consent Informed consent was obtained from all indi- their assessment of the results obtained was increased over vidual participants included in the study. that achieved by only visually inspecting CBCT images. Human and Animal Rights All procedures performed in studies Particularly, in all the ablations (6/38, 15.8%) where the involving human participants were in accordance with the ethical intraprocedural registered CBCT showed residual tumor standards of the institutional and research committee and with the percentage greater than 15%, on the 24 h post-ablation 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. CECT the two radiologists visually identified residual tumor enhancement exactly where the CBCT predicted it, Open Access This article is distributed under the terms of the leading to the conclusion that if the proposed method had Creative Commons Attribution 4.0 International License (http:// been employed, and in these six tumors the second treat- creativecommons.org/licenses/by/4.0/), which permits unrestricted ment could have been avoided. In the 8/38 (21.1%) treat- use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a ments in which CBCT showed minimal (less than 14.3%) link to the Creative Commons license, and indicate if changes were amount of residual tumor volume, the 24 h post-ablation made. CECT did not detect any residual enhancement likely due to the very small amount of residual tumor and/or the presence of the peripheral rim of inflammation. 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World J treatment planning and monitoring. EXCLI J. 2016;15:406–23. Gastroenterol. 2015;21(2):517–24. 22. Ahmed M, Solbiati L, Brace CL, Breen DJ, Callstrom MR, 31. Iwazawa J, Hashimoto N, Mitani T, Ohue S. Fusion of intra- Charboneau JW, Chen MH, Choi BI, de Bae`re T, Dodd GD 3rd, venous contrast-enhanced C-arm CT and pretreatment imaging Dupuy DE, Gervais DA, Gianfelice D, Gillams AR, Lee FT Jr, for ablation margin assessment of liver tumors: a preliminary Leen E, Lencioni R, Littrup PJ, Livraghi T, Lu DS, McGahan JP, study. Indian J Radiol Imaging. 2012;22(4):251–3. Meloni MF, Nikolic B, Pereira PL, Liang P, Rhim H, Rose SC, http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png CardioVascular and Interventional Radiology Springer Journals

A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time Intraprocedural Three-Dimensional Assessment of Ablative Treatments of Liver Malignancies

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Springer Journals
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Copyright © 2018 by The Author(s)
Subject
Medicine & Public Health; Imaging / Radiology; Cardiology; Nuclear Medicine; Ultrasound
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0174-1551
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1432-086X
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10.1007/s00270-018-1909-0
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29492634
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Abstract

Cardiovasc Intervent Radiol (2018) 41:1049–1057 https://doi.org/10.1007/s00270-018-1909-0 CLINICAL INVESTIGATION INTERVENTIONAL ONCOLOGY A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time Intraprocedural Three-Dimensional Assessment of Ablative Treatments of Liver Malignancies 1 1 2,3 1 • • • • Marco Solbiati Katia M. Passera S. Nahum Goldberg Alessandro Rotilio 4 4 4 4,5 • • • Tiziana Ierace Vittorio Pedicini Dario Poretti Luigi Solbiati Received: 1 August 2017 / Accepted: 17 February 2018 / Published online: 28 February 2018 The Author(s) 2018. This article is an open access publication Abstract Results Registration quality was high for both radiologists Aim To evaluate a novel contrast-enhanced cone-beam (R1: 4.3 ± 0.6, R2: 4.4 ± 0.5; p = 0.87). Comparisons computed tomography (CE-CBCT) registration method for between the registration of pre-ablation CECT with CE- accurate immediate assessment of ablation outcomes. CBCT versus post-ablation CECT regarding the position of Materials and Methods Contrast-enhanced computed the ablated area to the treated target (R1: 4.4 ± 0.6, R2: tomography (CECT) was registered with CE-CBCT by 4.6 ± 0.4) and treatment outcome (R1: 4.5 ± 0.5, R2: applying semiautomatic landmark registration followed by 4.6 ± 0.4) were equivalent (p[ 0.35). Increased confi- automatic affine and non-rigid registration to correct for dence was noted when using fusion (R1: 4.6 ± 0.4, R2: respiratory phase differences and liver deformation. This 4.6 ± 0.4; p = 0.84). Moreover, in 6 ablations (15.8%) the scheme was retrospectively applied to 30 patients who intraprocedural registered CBCT showed residual tumor underwent 38 percutaneous microwave liver ablations. precisely where identified on the 24 h post-ablation CECT. Three datasets were obtained for each case: (1) conven- Conclusions Combined CE-CBCT holds the potential to tional CECT scans 24 h before ablation, (2) intraprocedural change the current workflow of mini-invasive cancer local CE-CBCT scans, and (3) CECT scans 24 h post-ablation. treatments. Given earlier visual identification of residual Using a five-point scale, two experienced radiologists tumor post-ablation, this includes potentially eliminating qualitatively assessed registration quality, equivalence of the need for some additional treatments. CE-CBCT assessment of ablation outcome to 24 h post- ablation CECT, and perceived increase of confidence using Keywords Interventional radiology  Microwave the fusion method to CBCT alone. Additionally, residual Ablation  Liver tumors  Cone-beam CT post-ablation tumor volumes were measured at both CE- CBCT and 24 h CECT and compared to the pre-CECT. Introduction & Marco Solbiati m.solbiati@endo-sight.it Image-guided ablation using radiofrequency or micro- R&D Unit, R.A.W. Srl, Busto Arsizio, VA, Italy waves (MWA) has gained widespread attention and broad Department of Radiology, Hadassah Hebrew University clinical acceptance as minimally invasive treatment of liver Medical Centre, Jerusalem, Israel malignancies, particularly in non-surgical candidates [1–4]. Department of Radiology, Beth Israel Deaconess Medical Their success, however, relies strongly upon the operator’s Center, Boston, MA, USA skill and experience. Indeed, good clinical outcomes are Department of Radiology, Humanitas Clinical and Research predicated upon accurate selection criteria (i.e., tumor size, Center, Rozzano, Milan, Italy number, location, distance from major blood vessels), Department of Biomedical Sciences, Humanitas University, precise placement of ablative device(s), selection of Rozzano, Milan, Italy 123 1050 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… optimal ablation parameters, and a thorough and accurate Materials and Methods assessment of the completeness of treatment post-ablation. Lack of local tumor progression can only be confidently Pre-ablation Registration of CECT with CE-CBCT inferred when the ablation zone extends 5–10 mm beyond the entire tumor [5–7]. Real-time assessment could enable Registration of CECT with CE-CBCT consists of four immediate further treatment when this desired periabla- steps: (1) pre-ablation CECT re-sampling at CBCT reso- tional margin is not achieved, potentially avoiding subse- lution, (2) semiautomatic rigid registration, (3) automatic quent additional treatment sessions. affine registration followed by nonlinear registration, and Currently, many liver tumor ablations are performed (4) overlapping of pre-ablation CECT segmented over the using ultrasonography, where despite combined use of registered target on CE-CBCT. contrast-enhanced sonography and fusion imaging, imme- The semiautomatic rigid registration is based upon diate assessment of ablative margins can be hampered by selection of three corresponding landmarks visible in both incomplete three-dimensional evaluation [8, 9]. Likewise, image datasets. Here, intrahepatic blood vessels were when using CT guidance, the ablation margin is most often selected as these are closer to the target and have less risk assessed subjectively—comparing pre-ablation contrast- of deformity from respiratory motion than the outer con- enhanced CT (CECT) or MRI with post-ablation CECT. tour of the liver [16]. This step is necessary as CBCT and This is often accomplished solely by manually measuring CT images often do not completely overlap and automatic distances from the tumor edge or ablation zone to selected registration cannot correct this large mismatch. To correct landmarks in both studies. This is time-consuming and for different liver shapes, different breathing phases and does not allow precise, quantitative three-dimensional motion artifacts, subsequent affine and nonlinear registra- assessment of ablative margins, given the subjective spatial tions are automatically performed. For this procedure, CE- co-registration of pre-ablation tumor volume with post- CBCT is considered the fixed (i.e., template) imaging ablation necrosis. In order to overcome such limitations, modality with CECT the moving (i.e., superimposed) software for three-dimensional co-registration has recently image. To accomplish this, the CECT is warped upon the become available, but has yet to make a widespread impact CE-CBCT in order to achieve registration. The method is on this clinical need [10]. implemented using Insight Toolkit (ITK) libraries and Nowadays, contrast-enhanced cone-beam CT (CE- Elastix toolbox [17, 18]. Normalized mutual information CBCT) is increasingly used in local treatments of liver was used for registration as it offers the best performance malignancies, including both transcatheter chemoem- in cases of multimodality. Nonlinear registration is based bolization and percutaneous ablation. Despite poorer res- on B splines [17]. olution, CE-CBCT provides fast generation of volumetric images with lower radiation dose compared to conven- Protocol tional CT, enabling the interventionalist to plan and directly guide procedures based upon immediate assess- Our CECT-CE-CBCT co-registration algorithm was ret- ment of results achieved [11–15]. Yet, comparison of post- rospectively applied to 30 patients (22 males and 8 ablation CBCT with pre-ablation CECT scans is very females, aged 65–85 years) who underwent 38 percuta- cumbersome as CT and CBCT datasets differ with respect neous microwave liver ablations (MWA) (28 hepatocellu- to many parameters, and software providing fast and lar carcinomas (HCCs) in 22 patients and 10 cases of accurate three-dimensional co-registration of CECT and colorectal metastases (MET) in 8 patients). Tumor diam- CE-CBCT is currently not available. eters ranged from 0.7 to 3.3 cm (0.38–14.49 cc volume) To surmount this issue, we introduce here a novel (Table 1). One patient underwent two treatments, since in method that combines state-of-the-art image processing the first session one tumor was not fully ablated. algorithms to provide precise and fast spatial co-registra- For each case, three datasets were obtained: (1) con- tion of pre-treatment CECT with immediate post-treatment ventional CECT scans 24 h before ablation, (2) intrapro- CE-CBCT, to enable accurate assessment of ablative cedural CE-CBCT scans, and (3) CECT scans 24 h after margins in three dimensions immediately post-ablation. ablation. Pre- and post-ablation CT examinations were performed using a 64-slice scanner (GE Healthcare, Milwaukee, USA) after intravenous administration of 120–140 cc (mean, 129 ± 8) non-ionic contrast medium (iomeprol, Iomeron 300; Bracco, Milan, Italy) at 3 cc/s. Automatic bolus tracking (20 ml at 3 cc/s) was used, with monitoring scans 123 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… 1051 Table 1 Patients and treatment data Treatment Patient (male/ Tumor Tumor location Tumor volume Post-CT ablation Residual tumor volume 3 3 3 female, age) type (segment) (cm ) volume (cm ) percentage (cm %) 1 M, 71 HCC 6 0.8 19.1 0 2 M, 81 HCC 8 2.1 47.1 0.03 (1.4%) HCC 2 0.5 5.0 0.5 (100%) 3 M, 70 HCC 4 3.2 43.7 0.2 (6.3%) 4M,81 HCC 2 0.6 28.2 0.01 (1.2%) 5 F, 74 MET 7 11.2 39.2 0.2 (5.8%) 6 M, 75 HCC 2 13.6 18.2 0.6 (14.3%) 7 F, 80 HCC 4 0.9 3.0 0 8M,85 HCC 5 11.7 25.0 3.3 (28.3%) 9 M, 70 HCC 8 4.8 10.5 0 10 M, 71 HCC 5 1.1 5.3 0 11 M, 76 MET 8 0.5 2.9 0.01 (12.8%) 12 M, 82 HCC 6 0.5 3.3 0 13 M, 71 MET 4 1.0 5.2 0 14 M, 80 HCC 4 11.1 35.7 1.3 (11.5%) 15 F, 65 MET 2 1.0 15.4 0.6 (58.1%) 16 M, 79 HCC 8 1.5 9.7 0 HCC 2 2.5 9.3 0 17 M, 77 HCC 3 9.4 23.9 0 18 M, 70 HCC 5 1.4 2.9 0 HCC 4 5.0 10.0 0 19 F, 83 HCC 8 2.8 4.0 0 20 F, 76 HCC 8 0.6 3.7 0 HCC 4 0.8 5.3 0 21 M, 81 HCC 5 4.7 12.0 0 22 F, 72 HCC 6 5.7 7.6 0.6 (10.2%) 23 M, 81 HCC 2 6.9 13.0 1.7 (24.2%) 24 M, 72 HCC 4 14.5 20.9 0 HCC 3 0.8 4.0 0.8 (100%) 25 M, 82 MET 2 10.3 22.9 0 26 M, 81 HCC 2 0.4 18.8 0 27 F, 75 HCC 5 2.5 6.6 0 HCC 2 1.2 7.0 0.4 (31.7%) 28 M, 78 MET 7 0.8 3.8 0 MET 8 0.4 2.9 0 29 F, 78 MET 8 2.5 4.0 0 MET 2 1.1 5.3 0 30 M, 77 MET 2 0.6 3.0 0 Residual tumor volume means the volume of the portion of unablated tumor as a result of incomplete ablation The totally missed targets (italics) and the targets with a volume of unablated tumor ranging from 20 to 58.1% of the initial volume (bold) are highlighted Treatment 2 and Treatment 4 were performed in the same patient acquired starting after a delay of 8 s. Approximately 6–9 s venous phase scans automatically started 15 s after com- thereafter, the contrast enhancement threshold (90 HU) was pletion of the arterial phase scans. Both phases were per- reached within the ROI (i.e., the lumen of the descending formed with 3–5 mm collimation and 2–2.5 mm aorta), and arterial phase scans were acquired. Portal reconstruction intervals, with a matrix of 512 9 512 pixels, 123 1052 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… and in-plane pixel size of 0.48–0.86 mm (mean CT (1: [ 7 mm, 2: 5–7 mm, 3: 3–5 mm, 4: 1–3 mm, 5: 0.68 ± 0.07). \ 1 mm). Five to ten minutes following cessation of microwave Finally, evaluation of the radiologist’s perceived ablation, post-ablation CE-CBCT dataset volumes includ- improved confidence in achieving complete ablation over ing the entire patients’ livers were acquired at CBCT (Artis simple visualization of the CBCT image set without image zee, Siemens Healthcare, Erlangen, Germany) after intra- registration was performed using a 1–5-scale scoring sys- venous administration of 120 cc of iomeprol at 3 cc/s. tem (1: no confidence increase, 2: low 3: discrete/moderate Arterial and portal venous phase axial scans were triggered 4: high, and 5: very high). The results of all four gradings 3 and 30 s after the injection of contrast medium and by the radiologists were subject to inter-observer analysis, reconstructed perpendicular to the patient’s longitudinal including direct comparison using Student’s T test. axis. Scanning parameters were 1.2 m source detector distance, 1.5 rotation step, 5 s rotation duration, 200 total arc trajectory range, 128 images (projections), 0.36 Results microGy/frame radiation dose, and 2–5 mm reconstruction intervals. Each reconstructed CT slice had a 512 9 512 Whole liver imaging was possible in all patients, based pixels matrix, with an in-plane pixel size of 1.02–1.20 mm upon accurate pre-procedural patient centering. The aver- (mean 1.18 ± 0.3). Each 3D scan covered an approximate age time required to perform the entire procedure of volume of 250 9 200 9 200 mm. landmark selection and co-registration ranged from 30 to 120 s. An example of the registration achieved is shown in CT Image Preprocessing Fig. 1. The quantitative results of the clinical evaluation are For registration, the arterial phase scans were used as they summarized in Table 2. Overall, extremely high concor- provided the greatest enhancement of the tumors. dance was noted between both radiologists with identical Pre-ablation and post-ablation CECT images were fil- grades of 43.3, 37.4, 78.9, and 60.5% assigned for regis- tered with a diffusion filter in order to reduce noise [19] for tration quality, position, clinical indication, and confidence automatic segmentation of liver, tumor, and resultant improvement, respectively, and with no case noted of ablation zone. For liver segmentation, a fast marching and discordance by more than one category (Table 2). 3D geodesic active contour program identified and selected Registration quality was on average scored extremely the entire liver [20]. As a final preprocessing step that high for both radiologists (R1: 4.3 ± 0.6, R2: 4.4 ± 0.5, finalized the CECT segmentation, tumor and induced mean ± standard deviation; p = 0.87), with no grade 1 or coagulation necrosis were further segmented using a hybrid 2 observations recorded. Comparisons between the regis- of fuzzy c-means algorithm and random walkers method tration of pre-ablation CECT with CE-CBCT to pre-abla- based upon CT density [21]. tion CECT with post-ablation CECT for both position of the ablated area with the treated target (R1: 4.4 ± 0.6, R2: Clinical Evaluation 4.6 ± 0.4) and treatment outcome (R1: 4.5 ± 0.5, R2: 4.6 ± 0.4) were equivalent (p = 0.36 and 0.73, respec- Two radiologists, each with a history of more than 2000 tively). Finally, a demonstrably higher increase of confi- ablation procedures, performed, evaluated our method, dence was noted for both radiologists (R1: 4.6 ± 0.4, R2: based upon three criteria: registration quality, correspon- 4.6 ± 0.4; p = 0.84) when they could replace the simple dence of the assessments of ablation outcomes and per- visual inspection of CBCT images without any registration ceived increase of confidence for treatment evaluation. with the proposed method of spatial overlapping of CBCT Registration quality was assessed by visually comparing images with pre-ablation images. A full 75/78 of compar- images before and after the overlapping registration of pre- isons (96.1%) were rated as ‘‘high’’ or ‘‘very high’’ with no ablation CECT images over CE-CBCT images. Next, the grade 1 or 2 observations were noted by either radiologist radiologists evaluated the accuracy of post-ablation out- and only 3 of 78 observations (3.9%) rendered grade 3 as comes comparing pre-ablation CECT fused to intraproce- ‘‘discrete/moderate.’’ dural immediate CE-CBCT with that of 24 h post-ablation Moreover, with registration of pre-CECT with CE- CECT. Both registration quality and ablation outcomes CBCT the amount of residual post-ablation tumor volume assessments were performed according to a qualitative was measured. In 24/38 (63.2%) ablations, the registration five-point scale (1: poor—2: fair—3: satisfactory—4: did not show any residual tumor and for all 24/24 (100%) good—5: excellent). Spatial position accuracy was defined of them no residual tumor was also detected on the 24 h as displacement between the tumor location on the pre- post-ablation CECT (Fig. 2). In 12/38 (31.6%) ablations, ablation CT when overlapped to CBCT and post-ablation the intraprocedural registered CBCT showed residual 123 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… 1053 Fig. 1 Effects of image registration. Unregistered pre-CT (in purple substantial misalignment occurring before registration (manifest as a color) overlapped to CBCT (in green color) (first row) compared to purple shadow) was almost completely eliminated using our new registered pre-CT overlapped to CBCT (second row) for three fusion method despite the technical differences between the two representative slices of patient #1. The comparison shows that the different imaging modalities unablated tumor, ranging from 1.2 to 58.1% (mean Discussion 17.2 ± 16%) of the initial tumor volume. In 4/12 (33.3%) cases, the amount of unablated tumor ranged from 20 to We describe a novel registration method between post- 58.1% of the initial tumor volume and for all 4 of these the ablation CBCT and pre-ablation CECT scans that facili- 24 h post-ablation CECT showed a rim of residual tates intraprocedural treatment assessment. enhancement indicating incomplete ablation [22] (Fig. 3). Although CT and CBCT are both based upon radiation In the remaining 8/12 (66.7%) cases, the amount of and computed tomography, their datasets differ with unablated tumor detected by CBCT ranged from 1.2 to respect to many parameters including: the field-of-view 14.3% of the initial volume. In these 8 (100%), the 24 h focusing of interest, speed of rotation, susceptibility to post-ablation CECT did not detect any residual enhance- motion, different signal-to-noise ratios, image resolution ment. In the last 2/38 (5.3%) treatments, both intraproce- and CBCT scan artifacts that may lead to non-uniform dural registered CBCT and 24 h post-ablation CECT intensity images [23]. Additionally, liver parenchyma often showed that the target was completely missed (Fig. 4). undergoes significant deformation (particularly in cranial Thus, ultimately in 6/38 (15.8%) cases (4/38 (10.5%) segments) due to respiratory movement [24]. These issues with the amount of unablated tumor ranging from 20 to make co-registration of the two volume datasets non-intu- 58.1% and 2/38 (5.3%) with a completely missed target) itive and challenging. our CBCT fusion method identified the need for retreat- Prior studies addressing CBCT registration in different ment as confirmed by the post-ablation CECT. anatomic sites [25, 26], including liver [23, 27–29] have predominantly focused upon adaptive radiation therapy. Image fusion of pre-treatment CT with post-treatment CBCT for the assessment of ablation margins has been previously described, but has been performed through landmark rigid registration, which does not take into account modifications of liver and target tumor shape 123 1054 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… Table 2 Results of clinical evaluation Treatment Registration quality Tumor Target position (segment) Correspondence with post-CT Confidence improvement Position Clinical indication R1 R2 R1 R2 R1 R2 R1 R2 1 5 4 HCC 6 5 5 5 5 5 5 2 3 3 HCC 2 3 3 3 3 4 5 HCC 8 4 3 4 4 4 5 3 4 4 HCC 4 4 5 5 5 5 4 4 3 4 HCC 2 4 5 5 5 5 5 5 5 5 MET 7 4 5 4 5 5 5 6 5 5 HCC 2 5 5 5 5 5 5 7 4 5 HCC 4 5 4 5 5 5 5 8 5 4 HCC 5 4 5 4 5 5 4 9 5 5 HCC 8 5 5 5 5 5 5 10 4 5 HCC 5 5 4 5 5 5 5 11 5 4 MET 8 5 4 5 5 5 5 12 5 4 HCC 6 5 5 4 4 4 5 13 4 5 MET 4 4 5 5 5 5 4 14 2 3 HCC 4 4 4 4 4 4 3 15 3 3 MET 2 3 4 4 3 4 4 16 5 4 HCC 8 4 5 4 4 4 4 HCC 2 3 4 3 3 3 4 17 5 5 HCC 3 4 5 4 4 4 5 18 5 5 HCC 5 5 5 5 5 5 5 HCC 4 5 5 5 5 5 5 19 4 5 HCC 8 4 5 5 4 5 5 20 5 5 HCC 8 5 5 5 5 5 5 HCC 4 5 5 5 5 5 5 21 5 4 HCC 5 4 4 3 3 3 4 22 4 4 HCC 6 5 4 5 5 5 4 23 5 4 HCC 2 4 5 4 5 4 4 24 4 5 HCC 4 5 5 5 5 5 4 HCC 3 5 4 5 5 5 5 25 5 4 MET 2 5 5 5 5 5 4 26 3 4 HCC 2 5 4 5 4 5 5 27 5 5 HCC 5 4 5 4 5 4 5 HCC 2 4 5 4 5 4 5 28 5 5 MET 7 4 4 4 4 4 4 MET 8 5 4 5 5 5 5 29 5 5 MET 8 5 5 5 5 5 5 MET 2 5 5 5 5 5 5 30 4 5 MET 2 5 5 5 5 5 5 Average 4.3 4.4 4.4 4.6 4.5 4.6 4.6 4.6 Standard deviation 0.6 0.5 0.6 0.4 0.5 0.4 0.4 0.4 induced by patient breathing and/or movement—factors our algorithm surmounts these issues by providing auto- shown to impede ablation success [24, 30, 31]. However, matic rigid and non-rigid registration. 123 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… 1055 PRE-CT CBCT POST-CT Fig. 2 Demonstration of successful ablation treatment at CBCT. First 24-h post-ablation with CECT (post-CT) (with the pre-treatment HCC HCC of patient #2, studied with CECT before ablation (PRE-CT) colored in red). Both CBCT and post-CT show the ablated area (HCC indicated by yellow arrow), intraprocedural CBCT co-regis- entirely surrounding the target tered with PRE-CT (with the pre-treatment HCC colored in red) and POST-CT PRE-CT CBCT Fig. 3 Incomplete treatment detected by CBCT. Intraprocedural The medial portion (yellow arrows) of the HCC (colored in red) is not CBCT registered with PRE-CT in patient #8 of Table 1 shows partial entirely covered by the ablated area both on CBCT and on post-CT failure of the ablation treatment, as confirmed by the 24 h post-CT. Fig. 4 CBCT demonstration of PRE-CT POST-CT CBCT missed target. Comparison among pre-ablation CT (PRE- CT), intraprocedural registered CBCT, and 24 h post-ablation CT (post-CT) (second HCC of patient #2). After the first treatment, both CBCT and post- CT show that the HCC (colored in red and indicated by yellow arrows) is entirely located outside the volume of ablation (missed target) (top row). Most notably, the ablated area (indicated by the white arrows of the second row) is located caudally with respect to the actual target position (yellow arrows of the first row) both on CBCT and post-ablation CT. In the bottom row, the successful retreatment is shown, with the ablated area (yellow arrows) fully covering the target (red dot) 123 1056 M. Solbiati et al.: A Novel CT to Cone-Beam CT Registration Method Enables Immediate Real-Time… S. Nahum Goldberg performs unrelated consulting for Angiody- Equivalent quality and confidence were noted for both namics and Cosman Instruments. types of fusion images by the two radiologists. Further- more, despite substantial clinical experience, confidence in Informed Consent Informed consent was obtained from all indi- their assessment of the results obtained was increased over vidual participants included in the study. that achieved by only visually inspecting CBCT images. Human and Animal Rights All procedures performed in studies Particularly, in all the ablations (6/38, 15.8%) where the involving human participants were in accordance with the ethical intraprocedural registered CBCT showed residual tumor standards of the institutional and research committee and with the percentage greater than 15%, on the 24 h post-ablation 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. CECT the two radiologists visually identified residual tumor enhancement exactly where the CBCT predicted it, Open Access This article is distributed under the terms of the leading to the conclusion that if the proposed method had Creative Commons Attribution 4.0 International License (http:// been employed, and in these six tumors the second treat- creativecommons.org/licenses/by/4.0/), which permits unrestricted ment could have been avoided. In the 8/38 (21.1%) treat- use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a ments in which CBCT showed minimal (less than 14.3%) link to the Creative Commons license, and indicate if changes were amount of residual tumor volume, the 24 h post-ablation made. CECT did not detect any residual enhancement likely due to the very small amount of residual tumor and/or the presence of the peripheral rim of inflammation. 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Published: Feb 28, 2018

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