Radiological findings of porcine liver after electrochemotherapy with bleomycin

Abstract

Background Radiologic findings after electrochemotherapy of large hepatic blood vessels and healthy hepatic parenchyma have not yet been described. Materials and methods We performed a prospective animal model study with regulatory approval, including nine grower pigs. In each animal, four ultrasound-guided electroporated regions were created; in three regions, electrodes were inserted into the lumen of large hepatic vessels. Two types of electrodes were tested; variable linear- and fixed hexagonal-geometry electrodes. Ultrasonographic examinations were performed immediately and up to 20 minutes after the procedure. Dynamic computed tomography was performed before and at 60 to 90 minutes and one week after the procedure. Results Radiologic examinations of the treated areas showed intact vessel walls and patency; no hemorrhage or thrombi were noted. Ultrasonographic findings were dynamic and evolved from hyperechogenic microbubbles along electrode tracks to hypoechogenicity of treated parenchyma, diffusion of hyperechogenic microbubbles, and hypoechogenicity fading. Contrast-enhanced ultrasound showed decreased perfusion of the treated area. Dynamic computed tomography at 60 to 90 minutes after the procedure showed hypoenhancing areas. The total hypoenhancing area was smaller after treatment with fixed hexagonal electrodes than after treatment with variable linear geometry electrodes. Conclusions Radiologic findings of porcine liver after electrochemotherapy with bleomycin did not show clinically significant damage to the liver, even if a hazardous treatment strategy, such as large vessel intraluminal electrode insertion, was employed, and thus further support safety and clinical use of electrochemotherapy for treatment of hepatic neoplasia.

Keywords: computed tomography; electrochemotherapy; hepatic vessels; liver; pig; ultrasound.

Figure 1

B-mode ultrasonography. (A) Position of the variable linear geometry electrode in the left middle hepatic vein (arrow). (B) Hyperechogenic microbubbles (arrows) observed immediately after electrochemotherapy (ECT) along the track of the linear electrode. (C) Hyperechogenic microbubbles observed immediately after ECT along the tracks of hexagonal geometry electrodes (arrows). (D) In the next minutes, the hepatic parenchyma of the treated area becomes hypoechogenic (yellow arrow), and hyperechogenic microbubbles (red arrow) start to diffuse.

Figure 2

Doppler and contrast-enhanced ultrasonography. (A) Color Doppler in the left middle hepatic vein (blue) immediately after electrochemotherapy (ECT). Hyperechogenic microbubbles (arrow) can be noted. (B) Contrast enhanced ultrasound (CEUS) immediately after ECT and at 13 seconds after contrast administration; the position of the electrode is circled. (C) CEUS at 4 minutes after ECT and at 24 seconds after contrast; the larger vessel can be recognized (arrows). (D) CEUS at 5 minutes after ECT and at 14 seconds after contrast; a perfusion curve is shown.

Figure 3

Dynamic CT study, area treated with hexagonal electrodes is circled; note that hypoenhancing areas are most clearly seen 30 seconds after arterial phase. (A) Pre-contrast. (B) Arterial phase. (C) At 30 seconds after arterial phase. (D) At 60 seconds after arterial phase. (E) At 90 seconds after arterial phase.

Figure 4

(A) Electrochemotherapy (ECT) of the liver with linear electrodes. Left Figure is a CT image, where a distance between the hypoenhancing tracks of 2 cm can be noted. Right Figure is numerical model of electric field distribution in linear electrodes. Middle Figure shows electric field distribution superimposed on the CT image. (B) ECT of the liver with hexagonal electrodes. Left Figure is a CT image and right Figure is numerical model of electric field distribution in hexagonal electrodes. Middle image shows electric field distribution superimposed on the CT image. (C) Multiplanar reconstruction (MPR) of Figure 4A .The hypoenhancing area is circled. Note the larger vessel in the middle of the hypoenhancing area in coronal reconstruction.

Figure 5

Computed tomography. Hypoenhancing areas after electrochemotherapy (ECT). (A) Variable linear geometry electrodes. Hypoenhancing track to the caudal vena cava (yellow arrow), hepatic vein (green arrow), portal vein (red arrow) and treated hepatic parenchyma of the left liver lobe (blue arrow). (B) Fixed hexagonal geometry electrodes. Hypoenhancing tracks toward the caudal vena cava (yellow circle), hepatic vein (green circle), portal vein (red circle) and when inserted only into hepatic parenchyma (blue circle).

Figure 6

Computed tomography. (A) Left middle hepatic vein, three successive slices, hypoenhancing tracks in contiguity with the treated vessel (circled) and the vessel wall and patency were not affected. (B) Delineation of nonenhancing regions (white) and computer program determination of the area (in mm2) and attenuation (in Hounsfield units or HU) of the region. The red circle indicates untreated hepatic parenchyma, excluding large vessels. (C) One week after electrochemotherapy (ECT) with linear electrodes, narrow hypoenhancing tracks were observed (red arrow).

Figure 7

Histology of hepatic parenchyma immediately after electrochemotherapy (ECT). Fibrin thrombus in the lumen of a small venule (arrow). (A) H&E, 10x. (B) H&E, 20x.