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1 Department of Radiology, Osaka City University Graduate School of Medicine,
1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
2 Second Department of Surgery, Osaka City University Graduate School of
Medicine, Abeno-ku, Osaka 545-8585, Japan.
Received January 25, 2004;
accepted after revision May 6, 2004.
Address correspondence to A. Yamamoto.
Abstract
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SUBJECTS AND METHODS. We prospectively studied 20 patients (19 men and one woman) who underwent radiofrequency ablation of lung tumors. Pre- and postoperative MRI examinations were performed in all 20 patients, and during 17 radiofrequency ablation sessions, sonography was used to monitor whether microemboli were generated.
RESULTS. Radiofrequency ablation was technically feasible for the treatment of selected pulmonary tumors. Microemboli, which were believed to represent microbubbles, were seen on sonography during three of the 17 radiofrequency ablation sessions. They were rarely observed when a lung tumor was small, the treatment session was brief, and the radiofrequency emission power was low. No new area of abnormal intensity was seen on postoperative MRI in all 20 patients. Although the microemboli were observed, MRI could not confirm infarction.
CONCLUSION. We concluded that cerebral infarction as a result of microbubbles generated during radiofrequency ablation of lung tumors has a low possibility of becoming a clinical problem.
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Radiofrequency Ablation Technique
Radiofrequency ablation was indicated in these patients because of medical
comorbidities, prohibitive pulmonary reserve, or refusal of surgery.
Twenty-five lung tumors in 20 patients were treated with radiofrequency
ablation. The treated tumors included lung cancer recurrence (n = 5)
(non–small cell lung carcinoma) and metastatic lung tumor from
extrathoracic malignancy (n = 20; renal cell carcinoma, esophageal
carcinoma, leiomyosarcoma, colon carcinoma, thyroid carcinoma, bladder
carcinoma, and malignant myxoid tumor)
(Table 1). Radiofrequency
ablation was performed in a CT room with the patient under local anesthesia.
Scans were obtained through the lung at a slice thickness of 2 mm using a CT
unit (Xvigor, Toshiba). Radiofrequency was generated by a RF2000 unit (Boston
Scientific).
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After a 23-gauge localizing needle was used to define the proper route for the subsequent tandem insertion, a needle electrode (LeVeen Needle Electrode, Boston Scientific) was inserted. We used a 15-gauge LeVeen Needle Electrode with either eight retractable distal hooks that can deploy to the full length of 2 cm or 10 retractable distal hooks that can deploy to the full length of 3 cm. After a patient was placed in the prone or supine position on the CT table, grounding pads were placed on both of the patient's thighs. Radiofrequency ablation was performed with the emission power initially set at 20–30 W and increased by 5 W every 2 min. The radiofrequency energy was applied until it automatically stopped (roll-off) because of increased resistance caused by tissue dehydration. The maximum emission power was 80 W.
Sonography
The carotid artery was monitored during 17 of the 20 radiofrequency
ablation sessions using a sonography unit (LOGIQ500, GE Yokogawa Medical; a
probe [LA39, GE Yokogawa Medical]; B-mode, 8.7 MHz; Doppler, 5.0-MHz linear
transducer). If possible (depending on the patient's position), the right or
left common carotid artery was monitored before and throughout radiofrequency
ablation and recorded on videotape for later analysis. Of the 17 sessions,
four sessions were monitored using B-mode sonography only and 13 using B-mode
and Doppler sonography (Table
1). On B-mode sonography, emboli were observed visually. On
pulsed-wave Doppler sonography, emboli with high signal intensities above and
below the background Doppler signal (vertical spike) and a characteristic
harmonic quality were confirmed both visually and auditorily. The relationship
between the existence of microemboli and the basic data for the radiofrequency
ablation session—that is, patient age, tumor size, maximum emission
power, treatment time, and distance from the major pulmonary vein (> 5 mm
on CT)—was compared and assessed.
MRI
Diffusion-weighted imaging and FLAIR imaging were performed in all 20
patients both preoperatively and postoperatively (
24 hr after operation
[median time, 19.2 hr; range, 16–22 hr]). Diffusion-weighted imaging was
performed at 1.5 T (Signa, GE Healthcare) using a single-shot echo-planar
spin-echo technique. A maximum diffusion sensitivity of a b value of 1,000
sec/mm2 was applied to three orthogonal planes (x, y, z).
Axial images were obtained at 20 levels (TR/TE, 5,000/102; number of
excitations, 1; section thickness, 5 mm; intersection gap, 1.5 mm; field of
view, 20 cm; matrix, 128 x 128; bandwidth, 78 kHz). FLAIR imaging was
also performed at 1.5 T (Signa, GE Yokogawa Medical), and axial images were
obtained at 20 levels (9,002/150; number of excitations, 1; inversion time,
2,000 msec; section thickness, 5 mm; intersection gap, 1.5 mm; field of view,
20 cm; matrix, 256 x 192; bandwidth, 16 kHz).
Two radiologists who were blinded to the clinical status of the patients independently interpreted the images. The criterion for a new abnormal-intensity area on postoperative MRI was a high-signal area of more than 10 mm2 excluding the existing area shown on preoperative MRI or a high-signal area at two contiguous levels.
Statistical Analysis
Interobserver variability was determined by kappa statistical tests
[10]. The relation between the
existence of microemboli and the basic radiofrequency ablation session data
was investigated. Between the patients with microemboli and those without
microemboli, a pretest for comparing variance of the two distributions
(homoscedasticity) was performed. The Student's t test was chosen
when the variances of the two distributions were equal, and the Welch
t test was chosen when not equal. The nominal level was 0.05.
Confidence interval limits were derived using standard statistical
methods.
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None of the patients was shown to have carotid artery microemboli on
preoperative sonography. In three of the 17 patients (patients 7, 13, and 20),
highly echoic emboli were displayed and a visible vertical spike was observed
above the background Doppler signal. A microembolus was seen before roll-off
in one patient (patient 13), and microemboli were seen approximately 5 min
after the start of ablation in two patients (patients 7 and 20). One
microembolus was observed in patient 13, and multiple microemboli were
observed throughout the procedure in patients 7 and 20 (e.g., 
100 per
minute in patient 7) (Fig. 1A).
When ablation was stopped, the microemboli were not observed. Preoperative
results of diffusion-weighted imaging and FLAIR imaging were normal. On
postoperative diffusion-weighted imaging and FLAIR imaging, no new area of
abnormal intensity was identified in any of the patients by either of the two
observers (
= 1.00).
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Sonography and MRI studies were performed in 13 patients. No new area of abnormal high intensity was observed on MRI in any of the patients including patient 13 in whom one microembolus was seen and patients 7 and 20 in whom multiple microemboli were seen on sonography (Figs. 1B and 1C). We found a relationship between the existence of microemboli and the basic data (Table 2) about the radiofrequency ablation sessions—that is, tumor size (Fig. 2A), maximum emission power (Fig. 2B), and treatment time (Fig. 2C).
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In three (17.6%) of our 17 patients, microemboli were seen during ablation. In our study, microemboli with high signal intensities above and below the background Doppler signal (vertical spike) and a characteristic harmonic quality were confirmed both visually and auditorily (Fig. 1A). These findings are similar to those reported by Rose et al. [14] and are considered to be microbubbles.
Rose et al. [14] reported that microbubbles were observed during radiofrequency ablation in all three patients in their study, which does not correspond to our findings. This discrepancy might be because the generating frequency in our study was low compared with that reported by Rose et al. They set the initial emission power at 25–40 W and increased it by 5–10 W per minute, whereas we set the initial emission power at 20–3 W and increased it by 5 W every 2 min.
We set the maximum power output to be less than 80 W in order not to expose the tumor to high temperature for a long time, and we raised the output more gradually than Rose et al. [14]. We think that the differences in the emission power settings seen in the study conducted by Rose et al. and our study contributed to the different frequencies of microemboli generation. The tumor size was larger (p < 0.0100), maximum emission power was higher (p < 0.0149), and treatment time was longer (p < 0.0183) in patients with microemboli than in those without microemboli. Moreover, the distance from the major pulmonary vein (> 5 mm on CT) was considered to be unrelated to microemboli generation. These findings suggest that the possibility of microbubbles being generated is increased when the maximum emission power is high. Rose et al. reported that unenhanced CT of the brain performed after lung ablation shows no abnormal findings in patients with microemboli.
We performed diffusion-weighted imaging because a more sensitive diagnosis of acute cerebral infarction could be made using diffusion-weighted imaging than using CT or conventional MRI [15]. Diffusion-weighted imaging can detect parenchymal changes in humans within 40 min after onset [16] and can continue to detect them for at least 1 week [17]. We performed diffusion-weighted imaging within 24 hr after the lung radiofrequency ablation and think that this timing is appropriate for determining whether any areas of unusual signal intensity are present. Preoperative MRI was performed to exclude the presence of a silent embolism [18].
In our study, postoperative MRI showed no new abnormal high-signal area in any patients including those in whom microemboli were observed on sonography. We believe that there are four possible explanations for this discrepancy. First, there is a possibility that a transient arterial occlusion was improved at an early stage. Second, the early dissolution of microbubbles in the plasma was observed in the carotid artery. The composition of microbubbles was unknown. They are reported to occur from vapor formation of blood or water, nitrogen or nitrous oxide gas, and carbon dioxide. Intrahepatic vascular gas has been observed on real-time hepatic sonograms, but not on preoperative cardial Doppler sonograms [19]. Third, emboli that reached the brain were very small, and they did not cause arterial infarction. In a mouse model, microbubbles were reported to be 3–8 µ m [9]. Microbubbles are used as sonographic contrast agents, and their average size is 35.5 µ m [20]. When the size of microbubbles is approximately 35.5 µ m, the possibility that they might cause cerebral infarction is low. Fourth, embolic events in patients with early reperfusion would not be detected on MRI performed within 24 hr of radiofrequency ablation. There are many reports about acute stroke syndrome with fixed neurologic deficit and false-negative findings of diffusion-weighted imaging in human and animal models [21–23]. Negative findings on diffusion-weighted imaging of the brain cannot always exclude the possibility that a patient has acute cerebral ischemia.
An upper bound for the incidence of an event with zero occurrences in a study sample is estimated to be less than 10% in patients with an abnormal-intensity area detected on diffusion-weighted imaging using a Bayesian estimate with a noninformative beta (p < 0.05) [24]. In our institute, radiofrequency ablation of lung tumors had been performed 60 times. Further study using a larger number of subjects is required, but our results indicate that cerebral infarction due to microbubbles during radiofrequency ablation of lung tumors has a low possibility of becoming a clinical problem.
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