A Cone-Beam Volume CT Using a 3D Angiography System with a Flat Panel Detector of Direct Conversion Type: Usefulness for Superselective Intra-arterial Chemotherapy for Head and Neck Tumors

Case Selection and Classification

Between April 2005 and January 2006, 29 consecutive patients, who underwent the superselective intra-arterial chemotherapy for histopathologically confirmed head and neck tumors, were prospectively included in this study. Because in 6 patients with carcinomas of the mouth the arterial infusion of indigocarmine dye provided the exact identification of tumor feeding arteries, the interventional radiologists decided that the intra-arterial cone-beam CT was unnecessary for these patients. Thus, the study population consisted of 23 patients (18 men and 5 women; age range, 45–85 years; mean age, 66.9 years). Before DSA, enhanced MR imaging and/or CT was performed in all 23 of the patients.

Imaging System

All of the angiography examinations (DSA and cone-beam CT) were performed by using an angiography system with an FPD of direct conversion type on a motorized C-arm (Safire; Shimadzu, Kyoto, Japan). This detector has a pixel pitch of 150 μm and an array format of 1472 × 1472 pixels, covering a detector size of 22 × 22 cm². An amorphous selenium film, approximately 1000-μm thick, is used as an x-ray converter. The cone-beam CT acquisition consists of synchronized x-ray exposure and a panel readout under the continuous rotation of the C-arm. The 3D datasets were obtained from single rotation with a FOV of 23 × 23 cm using the floor-mounted C-arm. This series covers a total angular range of 195° around patients, with the rotation of 20° per second during the administration of contrast material. A total of 280 projections with x-ray parameters of 65 kV and 695 mA were acquired at 30 frames per second with 1024 × 1024 matrices. The distance between the focal spot and the detector was approximately 115 cm and that between the focal spot and isocenter was approximately 73 cm.

The image datasets were immediately transferred to a workstation (DAR-5000, 3D-ANGIO option V3.0; Shimadzu), where a volume dataset was reconstructed in a CT-type dataset consisting of many sections with the thickness of voxel size and visualized with volume-rendering technique as 3D and multiplanar reconstruction images. With isotropic voxels, the length of the volume of interest in the patient's longitudinal axis (z axis) is 512 times the voxel side length (a voxel side length of 0.254 mm and the 512 × 512 matrix; the column has a dimension of 13 cm × a length of 13 cm). Volume images were available approximately 5 minutes after volume data were transferred to a workstation. Images were displayed on the host personal computer (immediately outside the operating room) and on an in-room display, and radiologists could independently examine the desired cross-section images on the workstation from axial or coronal view when they required further information to evaluate the tumors.

Angiography Protocol

All of the procedures were performed by 1 of 2 experienced interventional radiologists (S.K., N. Ohnari, with 11 and 20 years of experience in interventional radiology, respectively) at our institution after written informed consent was obtained from each patient. The study was approved by our institutional review board.

Using the Seldinger technique, the tip of a 5F catheter was guided from the femoral artery to the descending aorta. For DSA, all of the patients underwent cerebral angiography that included the unilateral or bilateral common carotid angiography to evaluate the vascularity of the head and neck tumors and the vascular anatomy. Then, the interventional radiologists underwent the selective catheterization distal to the external carotid artery by use of a 2.3F microcatheter, and the DSA was performed. For all of the DSAs, the contrast material (Iopamilon 300; Schering, Berlin, Germany) was manually administered using a syringe. If the tumor was present in either the tongue or oral cavity (buccal, gingival, and palatal surfaces), the feeding vessels were identified by staining the tumor after slow arterial infusion of 1.5 mL of indigocarmine dye. During the injection of indigocarmine dye, we observed whether the tumor was stained, and, if so, which part was stained.¹ Then, the cone-beam CT was performed in the same tip of the catheter as the DSA, when the interventional radiologists required the further information according to a tumor in performing a superselective intra-arterial chemotherapy. The start of contrast material injection, the volume, and the injection rate of contrast material were determined based on work performed previously in the DSA so that the contrast material filled the artery and demonstrated tumor staining throughout the rotational angiography. For rotational angiography, a total of 5.5–1.1 mL of the contrast material containing 100 mg/mL of iodine, which was diluted by the saline, was automatically administered with a scanning delay of 1 second at a rate of 0.5–1.0 mL/s using a power injector (Autoinjector 120S; Nemoto Kyorindo, Tokyo, Japan) during the entire acquisition.

Except for the treatment in cervical lymph node metastasis, the intra-arterial chemotherapy consisted of cisplatin and carboplatin administered at doses of 100 and 450 mg/m² for patients under 65 years of age, respectively. The dose of antitumor agent was reduced for patients older than 65 years or patients with adverse factors (renal dysfunction, liver dysfunction, leukopenia, thrombocytopenia, etc). Therefore, regimens of the intra-arterial chemotherapy varied, and the total doses administered in the treatment had a range for superselective cisplatin-carboplatin (290–540 mg) and for superselective cisplatin (30–100 mg). When multiple feeders existed, the dose of antitumor agent for each feeder was determined by the percentage of tumor stained with DSA and cone-beam CT on each vascular injection. When no spread of the contrast material throughout the entire tumor was confirmed on cone-beam CT, the superselective intra-arterial chemotherapy was not performed. As a result, the final plan for superselective intra-arterial chemotherapy was formulated based on the findings of DSA and cone-beam CT by interventional radiologists.

Image Analysis

We assessed the usefulness of cone-beam CT in conjunction with the DSA. Two radiologists (N. Ohnari and J.M.), who did not take part in image manipulation, independently reviewed the DSA and cone-beam CT. These radiologists were only informed of the final diagnoses of the lesions but were blinded to the angiography findings (injecting indigocarmine testing), physical examination results, and laryngoscopy reports. The radiologists first assigned scores to the DSA on hard-copy films alone and then immediately assigned scores to the cone-beam CT obtained in the same patient. The DSA and cone-beam CT were always evaluated in conjunction with the preinterventional CT and/or MR imaging studies. After independent interpretations were performed, the differences in assessing both radiologists were resolved by consensus. The cone-beam CT was displayed on a diagnostic monitor (Flexscan L365; EIZO NANAO, Ishikawa, Japan), and these radiologists could examine the desired cross-section images on the workstation from the axial or coronal view, when they required further information to evaluate the tumor.

For both the DSA and cone-beam CT, the following score was used to evaluate the diagnostic value regarding the tumor feeding arteries: score 1, excellent; score 2, adequate; score 3, less than adequate for diagnosis; and score 4, not diagnostic. In an attempt to predict the extent to which neighboring normal tissue had been exposed by the intra-arterially administered antitumor agent, these radiologists also evaluated the cone-beam CT for the extent of contrast material perfusion as follows: 1, excellent (the extent of contrast material perfusion was clearly visualized and perfusion contrast appears high); 2, good (satisfactory visualization but perfusion contrast somewhat reduced); 3, adequate (visualization of the extent of contrast material perfusion still sufficient); 4, insufficient visualization; and 5, not visible. To evaluate the level of interobserver agreement of scores of image quality, a Kendall W test was performed. The Kendall W coefficients between 0.5 and 0.8 were considered to indicate good agreement, and the coefficients higher than 0.8 were considered to indicate excellent agreement.

For 23 patients with head and neck tumor, one experienced interventional radiologist (either S.K. or N. Ohnari) and one radiologist (either Y.M. or J.M.), who assisted in the interventional procedure, evaluated the relative diagnostic image quality of cone-beam CT relative to that of the DSA by consensus and scored as follows: grade 1, cone-beam CT was better and changed the diagnosis with respect to tumor feeding arteries or treatment plan for superselective intra-arterial chemotherapy; grade 2, cone-beam CT was better and improved confidence in the diagnosis of tumor feeding arteries or therapeutic effect for superselective intra-arterial chemotherapy; grade 3, cone-beam CT was better but had no effect on the diagnosis or the treatment plan; grade 4, cone-beam CT was equivalent to the DSA; and grade 5, cone-beam CT was worse than the DSA. When the answers of the radiologists were scored as grade 1, they indicated how the additional information was provided by cone-beam CT. When directly testing the significance of differences between datasets consisting of ordinal evaluation scores, we used the Wilcoxon signed rank test.⁹

Interobserver Agreement

For rating of the diagnostic value with respect to tumor feeding arteries, the interobserver agreement between the 2 radiologists in rating the image quality parameter was excellent for both the DSA images alone and the conventional DSA with cone-beam CT, respectively, with Kendall W values (τ) of 0.83 and 0.91. For rating of the visualization of the extent of contrast material perfusion with cone-beam CT, the interobserver agreement between the 2 radiologists in rating the image quality parameter was good with Kendall W values (τ) of 0.75.