University of Pisa
Department of Translational Research and New Technologies
in Medicine and Surgery
Residency Program in Diagnostic Radiology
(2012-2017)
Chairman: Prof. Davide Caramella
Microwave ablation of liver tumors: how carbonization volume correlates
with wattage and duration of ablation.
Supervisor Candidate
Prof. Davide Caramella, MD Dr. Paola Scalise, MD
Academic Year 2015-2016
ABSTRACT
Purpose
To retrospectively evaluate the relationship between operative technical parameters, volume of carbonization and volume of ablation induced by microwave (MW) ablation of malignant liver tumors.
Materials and methods
We retrospectively reviewed the radiological charts and follow-up imaging evaluations of all the patients who underwent MW ablations for primary and secondary liver lesions at our Institution in the period between November 2015 and April 2017.
All the ablations were performed with a 2.45 GHz MW generator (HS AMICA, HS Hospital Service, Rome, Italy) using cooled mini-choked antennas (14-gauge and 16-gauge).
The following technical parameters were recorded for all the procedures: - power (P) released by the generator, expressed in watts (W);
- ablation time (T), defined as the duration of ablation, expressed in seconds (s); - cumulative energy deployed (total energy, TE), expressed in kilojoules (kJ),
calculated using the formula: TE = (P*T).
At computed tomography (CT) imaging performed at least 4 weeks after the ablative procedure, the hypo-attenuating area after contrast medium administration was considered representative of coagulative necrosis, while the central internal zone of hyper-attenuation in unenhanced scans was considered representative of carbonization.
Visual conspicuity of carbonization was qualitatively assessed in all cases; patient population was then sub-grouped according to well-definition and ill-definition of the carbonization zone.
Measurements of both carbonized and thermocoagulated areas were obtained at first follow-up CT scan. In particular, maximal post-procedural diameters (long axis - AP, short axis - LL and craniocaudal extension) and volumes of both the areas were calculated.
Correlation analysis were performed to compare diameters and volumes of both ablation and carbonization zones with time of ablation, power employed and total energy delivered.
Results
A moderately significant correlation between TE and the resulting volume of necrosis was found (ρ=0.52).
Bivariate analysis showed a strong linear relationship between necrosis and carbonization volumes (p< 0.0001). According to Spearman rank analysis there was a statistically correlation between necrosis and carbonization volumes (ρ=0.57).
The individual carbonization diameters considered as independent variables correlated with the equivalent necrosis diameters, in particular in AP and LL orientation (ρ=0.64 and 0.63, respectively).
Bivariate analysis showed a significant linear relationship between carbonization volume and reference ablation parameters; such relationship is preserved even in the subgroup of ill-defined carbonization area.
However, Spearman rank correlation did not show any correlation between carbonization diameters, carbonization volume and reference ablation parameters.
Conclusions
Carbonization represents a peculiar feature of MW ablation attributable to the higher temperatures reached in the treated lesion with respect to other ablative techniques. Our results showed a strong correlation between ablation and carbonization diameters and volumes, which might suggest that carbonization could represent an indirect marker of the overall tumoral tissue ablated by MW. Therefore, the identification of carbonization at imaging may represent a way to monitor the ablative procedure and to obtain a qualitative feedback of the treatment efficacy.
INTRODUCTION
Percutaneous microwave (MW) ablation represents an emerging therapeutic modality in the treatment of patients affected by primary and secondary liver neoplasms but not eligible for surgery due to tumor characteristics (lesion site and/or dimensions, multifocality/multicentricity), poor liver function and/or severe associated comorbidities. [1-7].
To ensure local tumor control and reduce local progression, an ablated area entirely encompassing the target volume is required, since cytotoxic temperatures must be reached in the whole lesion for adequate tumor destruction [8, 9].
In addition, a recommended minimum circumferential safety margin of nearby healthy liver ideally of 10 mm, but at least of 5 mm should be obtained [10-12]. However, an accurate monitoring of the ablated area (i.e., inclusion of the whole tumor and/or target in the ablation zone) is often technically challenging, even under imaging guidance [13, 14]. In addition, the desired final ablation dimensions often differ from the estimated ones, predicted in the pre-procedural planning according the to reference setting protocols provided by manufacturers, [14-18]. Furthermore, comprehensive a priori algorithms for the determination of the ablation parameters given tumour features are not available yet [19].
Therefore, alternative features of the ablated area should be investigated to assess completeness of ablation and effectiveness of tumor destruction.
MW typically produces an ellipsoidal zone of ablation, composed of an elliptical-shaped area of white coagulated tissue, where temperatures reached are approximately between 60 °C and 100 °C, and a central black area of carbonization in close proximity to the antenna where temperature exceeds 100 °C [8, 20, 21].
The ‘white zone’ and the ‘black zone’ together are considered representative of the overall area of successfully ablated tissue [21].
In literature, some Authors report the “black zone” of carbonization at postoperative imaging as a central zone of hyper-attenuation in unenhanced scans within the ablated area on computed tomography (CT) scans after treatment [20-24]. This finding represents a peculiar feature of MW ablation and attributable to the higher temperatures reached in the treated lesion respect to other ablative techniques [23]. The purpose of our study was to retrospectively evaluate the carbonization induced by MW ablation of malignant liver tumors and to assess if the selected operative technical parameters (wattage, time of ablation and energy deployed) correlate with carbonization volume.
MATERIALS AND METHODS
Patient population
A retrospective review of the radiological charts of all the patients who underwent MW ablations in the period between November 2015 and April 2017 for primary and secondary liver lesions was performed. Patient demographics and lesion characteristics were recorded in parallel with operative technical data.
Before treatment, all patients underwent contrast-enhanced CT and/or magnetic resonance (MR) abdominal examination after gadolinium administration. CT imaging was performed using a 64-row CT scanner (Light Speed VCT, General Electric®, Milwaukee, WI) or a 128-row CT scanner (Discovery CT750 HD, General Electric®, Milwaukee, WI) after contrast medium administration (100-120 ml; range of iodine concentration: 320–400 mg/ml; injection rate of 2.5-4 ml/s). MR imaging was performed with a 1.5T MR scanner (GE Sigma HDx 1.5T, General Electric®, Milwaukee, WI, USA) or a 3.0T MR scanner (MR750 Discovery 3.0T, General Electric®, Milwaukee, WI) after hepatobiliary contrast agents administration (0.1 mmol/kg (0.2 ml/kg) for gadobenate dimeglumine, and 0.025 mmol/kg (0.1 ml/kg) for gadoxetic acid; injection rate of 2.5-3 ml/s).
In all cases, patients’ eligibility to percutaneous treatment was assessed by a multidisciplinary team, composed at least by an interventional radiologist, a hepatologist, an oncologist and a hepato-biliary surgeon.
Microwave ablation procedure
All the ablations were conducted under deep sedation by interventional radiologists with at least 15 years of experience. All patients had an international normalized ratio (INR) < 1.5 and a platelet count >50 x 109/L.
All the ablations were performed with a 2.45GHz MW microwave generator (HS AMICA, HS Hospital Service, Rome, Italy) with maximum generator output of 140 W, using cooled mini-choked antennas (14-gauge and 16-gauge).
Each patient was treated with a single probe insertion and single uninterrupted energy application, without overlapping ablations, with the tip of the antenna in the same position.
Wattage and time of ablation were set according to location and characteristics of the target lesion, taking into account the guidelines provided by the manufacturer, and aiming to obtain an ablation area entirely including the lesion with a minimum safety margin of 5–10 mm.
Tract ablation was performed in all cases.
Energy data
In all the procedures, the following technical parameters provided from the generator were recorded:
- power (P) released by the generator, expressed in watts (W)
- ablation time (T), defined as the duration of ablation and expressed in seconds (s).
To quantify the energy released to the target, the cumulative energy deployed (total energy, TE), expressed in kilojoules (kJ), was calculated using the formula:
Assessment of the ablated area dimensions
As routinely performed at our Institution, first follow-up evaluation consisted in a CT scan scheduled at least 4 weeks after the ablation to evaluate the response to treatment. CT quadriphasic protocol included a non-enhanced scan followed by a triphasic (arterial, venous and delayed phases) acquisition of abdomen after intravenous injection of iodized contrast medium, after contrast medium administration (100-120 ml; range of iodine concentration: 320–400 mg/ml; injection rate of 2.5-4 ml/s).
The overall ablated zone corresponding to coagulative necrosis was identified as a hypo-attenuating area of non-enhancement [20].
In some cases, postoperative findings included a central zone of hyper-attenuation in unenhanced scans within the broader hypodense thermocoagulated area. This central hyperdense zone was considered representative of neoplastic tissue undergoing carbonization [14, 23] (Fig. 1-2). Its visual conspicuity was qualitatively assessed in all cases and patient population was then sub-grouped according to well-definition and ill-definition of the carbonized area (Fig. 3).
Measurements of both carbonized and thermocoagulated areas were assessed in non-enhanced and porto-venous phase after i.v. contrast medium administration, respectively.
In particular, maximal post-procedural diameters of both the areas were evaluated as following [14, 21]:
• long axis (i.e. maximal length, antero-posterior diameter - AP) was measured along the antenna trajectory;
• short axis (i.e. maximal width, latero-lateral diameter - LL) was calculated perpendicularly to the antenna course;
• cranio-caudal extension (i.e. cranio-caudal diameter – CC) was measured along the cranio-caudal axis.
The short and the long axis of the thermocoagulated necrotic area were used to calculate the sphericity of the ablation, defined (per Hines-Peralta et al) as the volume of ablation divided by the volume of a sphere using only the longest diameter. A sphericity index of 1.0 was indicative of a perfect sphere, while ellipsoids have indexes of less than 1.0 [15, 25].
The volumes (V) of both carbonized and necrotic zones were then estimated according to the following formula:
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Statistical analysis
All statistical computations were performed using the JMP 7.0 software (SAS Institute Inc. Cary, NC, USA).
All continuous variables are presented as mean±standard deviation (SD).
Bivariate analysis was used to evaluate: a) the relation between the carbonization volume and the necrosis volume obtained after microwaves ablation; b) the relation between the carbonization volume and P, T and TE delivered, respectively; c) the relation between the carbonization volumes, grouped according their visual conspicuity, and P, T and TE delivered, respectively. P-values of <0.05 were interpreted as statistically significant.
Spearman rank analysis was used to evaluate: a) the correlation between necrosis diameters and volume and antenna gauge, P, T and TE delivered, respectively, b) the correlation between carbonization diameters and volume and antenna gauge, P, T and TE delivered, respectively; c) the correlation between necrosis diameters and volume and carbonization diameters and volume; d) the relation between carbonization
volumes, grouped according the visual conspicuity, and P, T and TE delivered, respectively.
RESULTS
From November 2015 to April 2017, a total of 106 consecutive procedures of ablation were performed.
Among them, 10 procedures were excluded from our analysis due to lack of procedural data, antenna repositioning, multiple energy application and/or overlapping ablations. The final cohort included then a total of 96 procedures performed in 82 patients (65 males, 17 females, mean age 68.4 ± 10.3 years, min 46 years, max 85 years) affected by primary and secondary liver lesions.
Liver lesions included primary liver cancer (n= 74; hepatocellular carcinoma n=72; cholangiocarcinoma n=2) and liver metastasis (n=8, of which colorectal cancer (n=3), thyroid cancer (n=2), lung cancer (n=1), gastrointestinal stromal tumor (n=1), neuroendocrine tumor (n=1) metastasis. Demographic characteristics are summarized in Table 1.
All the ablations were performed using 14-gauge (n=43) or 16-gauge (n=53) antennas under imaging guidance: in the vast majority of procedures (87/96), the insertion of the antenna and the monitoring of the ablation were performed under ultrasound (US) imaging guidance, while the ablation procedure was supervised under CT guidance in the remaining 9 cases.
A summary of ablation parameters and resulting necrosis and carbonization measurements is provided in Table 2.
Mean T value was 267.4 s (±94.6, range 120–600 s); mean P value was 49.3 (± 9.4, range 30–80 W); mean TE deployed was 13.6 kJ (±6.9, range 4.2-48 kJ).
Mean pre-ablation diameters and volumes of the liver nodules were: - AP 18.2 mm (± 8.4; range 6–58 mm);
- CC 17.8 mm (± 8.8; range, 7–65 mm); - V 5.3 ml (± 14.23; range, 0.34–106 ml).
Mean diameters and volumes of thermal necrosis were: - AP 32.3 mm (± 10.4; range, 14–66 mm);
- LL 31.4 mm (± 11; range, 12–62 mm); - CC 32.3 mm (± 11.7; range, 15–80 mm); - V 19.6 ml (± 20.8; range, 1.8–123.6 ml). Mean diameters and volumes of carbonization were:
- AP 15.1 mm (± 7.3; range, 5–38 mm); - LL 14.1 mm (± 6.7; range, 4–41 mm); - CC 13.9 mm (± 7.1; range, 2–55 mm); - V 2.1 ml (± 3.1; range, 0.04–26.5 ml).
There was only a moderately significant correlation between TE employed and the resulting volume of thermal necrosis (ρ=0.52). No correlations were found between necrosis diameters (AP, LL and CC) considered as independent variables and reference ablation parameters (T, P and TE delivered) provided by the manufacturer (Fig. 4).
The gauge of the employed antenna did not show a correlation with necrosis diameters and volumes.
Bivariate analysis showed a strong linear relation between necrosis volume and carbonization volume (p< 0.0001); the confidence interval widens as the necrosis volumes and carbonization volumes increase, showing a statistical dispersion when the volume of necrosis was larger than 20 ml. (Fig. 5). According to Spearman rank analysis there was a statistically correlation between necrosis and carbonization volumes (ρ=0.57) (Fig. 6).
The individual carbonization diameters considered as independent variables showed a statistical correlation with the equivalent necrosis diameters, in particular in AP and LL orientation (ρ=0.64 and 0.63, respectively). (Fig 6).
Bivariate analysis was also carried out to verify the relation between the carbonization volume and the reference ablation parameters (P, T, TE). A linear positive statistical relation was obtained between carbonization volume and 1) P (p=0.0064); 2) T (p=0.0081); 3) TE (p=0.0022). (Fig 7). However, carbonization volume did not show a significant correlation with reference ablation parameters according to Spearman rank analysis. (Fig 8).
Bivariate analysis was used to verify the relation between the carbonization volume, grouped according the visual conspicuity, and the reference ablation parameters. The results showed linear positive statistical relation in both subgroups with p-values as follow:
- well-defined carbonization volume and P (0.0182), T (0.0336) and TE (0.0092) - ill-defined carbonization volume and P (0.0649), T (0.0072) and TE (0.0049). However the statistical dispersion of the ill-defined carbonization volume sample was wider than the one of the well-defined (Fig 9).
The overall average sphericity index for all ablations was 0.43 (± 0.18). TABLE 1 – Demographics and Imaging Guidance
Patient Sex Age Cancer Diagnosis Liver Segment Imaging Guidance
1 F 81 HCC S4 US 2 M 76 HCC S5 US 3 M 71 HCC S4 US 4 M 55 HCC S8 US 5 M 54 HCC S7 US 6 F 60 LUNG S6 US 7 M 68 HCC S8 US 8 F 66 THYROID S6 US 9 F 81 HCC S7 US 10 F 76 HCC S8 US 11 M 61 HCC S7 US 12 M 57 HCC S8 US 13 M 64 HCC S8 US 14 M 80 HCC S7 US 15 M 77 HCC S5 US 16 M 61 HCC S8 US 17 M 71 GIST S5 US
19 F 84 HCC S7 US 20 M 62 HCC S3 US 21 M 83 HCC S7 US 22 M 73 HCC S4 US 23 M 64 HCC S6 US 24 M 77 HCC S7 US 25 M 60 CCC S6 US 26 F 60 HCC S3 US 27 F 84 HCC S5-S6 US 28 M 69 HCC S7-S6 US 29 M 62 HCC S7-S6 US 30 M 66 HCC S8 US 31 M 48 HCC S2 US 32 M 60 HCC S7 US 33 M 57 HCC S8 US 34 M 70 HCC S8 US 35 M 83 HCC S8 US 36 M 72 HCC S8 US 37 M 59 NEUROENDOCRINE S5-S6 US 38 M 68 HCC S3 US 39 M 76 HCC S8 CT 40 M 69 HCC S7 CT 41 F 76 HCC S7-S6 CT 42 M 85 HCC S4 US 43 M 83 HCC S4 US 44 M 74 HCC S8 CT 45 M 58 HCC S8 US 46 M 70 HCC S8 US 47 M 50 HCC S8 CT 48 M 60 HCC S6 US 49 M 82 HCC S5-S6 US 50 F 75 HCC S8 US 51 M 49 HCC S7 US 52 F 64 HCC S7 US 53 F 80 HCC S4-S5 US 54 M 77 HCC S5 US 55 M 53 HCC S8 US 56 M 68 HCC S8-S5 US 57 M 75 HCC S8 US 58 M 46 THYROID S6 US 59 F 78 HCC S7 US 60 M 77 COLORECTAL S3 US 61 F 47 COLORECTAL S7 US 62 M 73 HCC S6 CT
63 M 76 COLORECTAL S4 CT 64 M 76 HCC S5 US 65 M 72 HCC S8 US 66 M 63 HCC S6 US 67 M 67 HCC S8 US 68 M 67 HCC S3 CT 69 M 67 HCC S8 US 70 M 69 HCC S7 US 71 M 54 HCC S6 US 72 M 81 HCC S8 US 73 F 71 HCC S2 US 74 M 65 HCC S8 US 75 M 63 HCC S8 US 76 M 57 HCC S5 US 77 F 47 HCC S2 CT 78 M 79 HCC S7 US 79 M 82 HCC S6 US 80 F 71 CCC S8 US 81 M 62 HCC S5 US 82 M 77 HCC S7 US HCC: Hepatocellular Carcinoma; GIST: Gastrointestinal Stromal Tumor
TABLE 2 – Ablation parameters and resulting necrosis and carbonization measurements
Ablation Carbonization
Procedure Power
(W) Time (sec) Energy (kJ)
Long Axis (mm) Short Axis (mm) Cranio-Caudal Axis (mm) Long Axis (mm) Short Axis (mm) Cranio-Caudal Axis (mm) 1 50 300 15 34 24 32 8 10 12 2 50 310 15.5 27 28 40 9 8 9 3 40 180 7.2 17 22 24 8 7 9 4 40 300 12 35 21 23 12 9 9 5 40 300 12 16 15 15 8 8 9 6 60 420 25.2 39 42 40 27 16 20 7 45 240 10.8 22 38 30 13 15 14 8 50 240 12 38 24 26 20 13 16 9 50 350 17.5 33 40 41 15 13 22 10 40 300 12 28 24 37 8 6 8 11 45 240 10.8 23 20 40 5 4 4 12 45 240 10.8 26 23 29 14 12 15 13 60 300 18 38 26 22 14 8 10 14 40 300 12 43 34 44 14 24 24 15 60 300 18 55 33 31 36 18 23 16 60 360 21.6 66 45 80 32 29 55 17 60 300 18 27 46 42 13 41 22 18 60 290 17.4 48 28 25 26 13 15 19 60 300 18 39 31 25 15 10 12 20 60 360 21.6 40 28 32 32 20 20 21 45 230 10.35 34 24 32 23 11 18 22 50 360 18 33 41 48 13 15 17 23 60 290 17.4 39 30 40 8 7 6 24 45 170 7.65 14 35 15 10 14 10 25 55 240 13.2 35 18 40 22 12 20 26 45 270 12.15 20 17 35 7 8 8 27 45 290 13.05 28 35 28 16 28 15 28 60 300 18 33 49 52 10 13 21 29 60 180 10.8 14 40 30 11 22 11 30 80 600 48 57 60 67 30 16 23 31 60 360 21.6 28 56 28 10 15 8 32 60 240 14.4 39 20 17 7 5 6 33 60 360 21.6 37 24 24 20 13 12 34 40 180 7.2 42 23 21 11 8 8 35 40 180 7.2 40 27 33 20 11 14 36 40 240 9.6 52 37 41 32 14 18 37 40 180 7.2 32 28 35 19 13 25 38 60 300 18 30 44 30 13 9 8 39 50 300 15 23 37 16 10 15 10
40 50 170 8.5 25 23 22 7 7 8 41 40 120 4.8 32 32 28 18 20 15 42 40 180 7.2 30 22 31 8 6 9 43 40 300 12 24 40 23 13 9 8 44 40 300 12 28 50 30 12 22 13 45 45 300 13.5 23 32 21 12 16 14 46 40 300 12 50 21 28 30 14 12 47 60 360 21.6 33 12 17 12 9 8 48 60 120 7.2 21 29 31 14 20 20 49 60 300 18 21 45 24 9 16 11 50 60 240 14.4 35 46 31 21 18 28 51 60 300 18 32 46 43 13 20 17 52 60 240 14.4 38 27 42 14 20 23 53 60 420 25.2 35 30 37 26 11 24 54 45 120 5.4 35 20 36 20 12 24 55 50 120 6 17 50 19 8 21 9 56 50 120 6 20 25 33 8 13 9 57 60 390 23.4 53 31 40 25 12 16 58 50 240 12 45 49 55 16 12 11 59 50 240 12 44 29 35 20 15 2 60 40 240 9,6 16 33 18 7 12 9 61 50 240 12 48 22 26 38 15 15 62 60 300 18 27 23 40 16 15 21 63 50 525 26.25 44 62 80 13 35 28 64 60 230 13.8 37 47 48 12 20 17 65 60 420 25.2 29 36 42 11 20 15 66 60 180 10.8 35 14 16 16 7 6 67 45 180 8.1 28 20 18 18 12 14 68 60 360 21.6 25 40 28 10 24 17 69 50 230 11.5 26 40 23 11 26 10 70 45 120 5.4 37 23 24 17 10 13 71 50 300 15 26 51 42 17 20 17 72 60 600 36 40 50 38 12 14 11 73 40 360 14.4 57 27 24 30 14 14 74 60 200 12 24 38 40 13 21 18 75 40 300 12 24 28 30 11 16 11 76 50 380 19 30 25 23 20 25 15 77 40 180 7.2 23 17 26 13 9 11 78 40 290 11.6 28 28 35 11 17 16 79 40 300 12 21 25 30 11 8 8 80 60 300 18 46 35 38 16 6 11 81 40 300 12 45 22 26 12 6 8 82 60 300 18 25 35 35 12 17 13 83 40 180 7.2 29 23 32 11 7 7
84 40 300 12 30 39 24 14 22 18 85 40 240 9.6 29 22 26 19 9 14 86 35 180 6.3 32 14 24 24 9 17 87 40 240 9.6 27 33 42 10 15 11 88 40 120 4.8 20 27 26 8 6 7 89 40 240 9.6 26 32 33 6 9 7 90 35 120 4.2 35 23 27 17 12 14 91 40 300 12 37 24 25 9 7 8 92 40 180 7.2 16 20 21 8 9 7 93 40 240 9.6 28 49 32 15 27 16 94 30 180 5.4 27 26 27 5 8 7 95 40 120 4.8 31 20 33 17 12 13 96 45 120 5.4 25 30 41 8 7 7
DISCUSSION
The present study found that, among the reference technical parameters (T, P and TE delivered) provided by the manufacturer, only the TE showed a moderately significant correlation with the volume of necrosis obtained (Spearman rank correlation, ρ=0.52). On the opposite, no correlations were found between the reference ablation parameters and the resulting necrosis diameters (AP, LL and CC) considered as independent variables.
Our findings confirmed previous evidences in literature regarding the existence of significant differences between the estimated ablation zone and the final one, mostly due to the fact that the reference values used to predict the ablative area are mainly derived from empirical ex vivo and in vivo animal models or by computer modelling [14, 18]. In particular, Winokur et al reported significant variability and smaller ablation zones than predicted by manufacturer charts, but they did not assess energy values as predictors of ablation zone size [18]. In addition, Shyn et al reported that even estimates of cumulative energy reaching the MW applicator and cumulative energy exiting the applicator after correction for reflectivity do not predict the ablation zone size better than manufacturer values, with greater variability of ablation zone diameters parallel to the applicator [14].
Even the gauge of the employed antenna did not correlate with necrosis diameters and volumes. In addition, we obtained elliptical rather than spherical ablation zone, with an average sphericity index for all ablations of 0.43 (± 0.18). By the measurement of the sphericity index, it is possible to evaluate he degree of heating in all dimensions from the ablation antenna [18]; however, our sphericity index value was lower than the ones reported in literature, confirming that the final ablated area might significantly differ from the ones estimated by reference values [15, 18].
However, the accurate prediction of ablation zone sizes still represents a pivotal point in preoperative planning of MW ablation to ensure the complete treatment of the tumoral lesion without harming nearby vital structures [14, 26]. Therefore, alternative parameters predicting the final dimensions of the ablated area should be investigated to ensure completeness of ablation and effectiveness of tumor destruction.
It is well known that multiple factors might have a role in determining volume and extension of the overall ablated area. [26-28]. Beyond technical elements related to the energy source and the antenna design, local tissue properties, (e.g. specific heat, electrical conductivity and water content), vascular perfusion and large vessel heat sink effects may deeply affect the overall energy absorption and have a predominant role on the resulting dimensions of the ablated area [14, 19, 25, 29, 30]. Even delayed effects of ablation may modify the resulting ablation zone [31], as well as the size and shape of the target tissue and the thermal properties of the medium surrounding the tissue in which the microwave thermal ablation is accomplished [26].
In addition, a tissue exposed to MW undergoes some structural modifications as temperature rises which irreversibly modify both dielectric and thermal properties, distribution of electromagnetic power deposition and heat conduction within the tissue, with consequently implications on size and shape of the induced thermal lesion [29, 30, 32-34].
Carbonization itself might substantially change the thermal properties of a tissue undergoing ablation [35, 36]. Carbonization typically develops when temperature exceeds 100 C in the course of ablation, hence in the tissue adjacent to the antenna active tip, where a large amount of the heat will be accumulated[20, 21, 26, 36]. When tissue temperature reaches approximately between 80 °C and 100 °C, water boiling, vaporisation and subsequent tissue charring represent the dominant heat
transfer processes [36] and the variation of tissue’s water content leads to a change in both the relative permittivity and electric conductivity [33].
Potentially, the “black” carbonized zone could be visually identified at postoperative imaging performed after MW ablation; in fact, tissue undergoing carbonization is sometimes visible at post-ablation CT scans as a central zone of hyper-attenuation in unenhanced scans [23]. Given this assumption, we wonder if carbonization could somewhat reflect the modifications of the tissue undergoing ablation and whether its assessment at imaging could add further information when evaluating the ablated tissue.
In our study, we found a strong relationship between necrosis and carbonization. In particular, bivariate analysis showed a strong linear relationship between necrosis volume and carbonization volume; in addition, as previously showed, the narrower was the ablated area, the stronger was the correlation, with a cut-off value of about 25 ml, suggesting that there is more variability if the ablation zone size increases. The strong relationship between necrosis and carbonization was also confirmed by Spearman rank correlation and remained valid not only for the corresponding volumes (ρ=0.57) but also for the single diameters themselves. In particular, the individual carbonization diameters considered as independent variables correlated with the equivalent necrosis diameters, especially in AP and LL orientation (ρ=0.64 and 0.63, respectively). On this basis, carbonization can be considered an indirect marker representative of the overall tissue ablated.
Based on these results, we then hypothesized if carbonization could represent a control parameter to be used in every day clinical practice to monitor the ablation itself. We then tested whether a relationship might be recognised between the operative technical parameters and the resulting carbonization volume. Each reference ablation parameter showed a significant linear relationship with the final
carbonization volume, and this relationship is maintained even in the subgroup of ill-defined carbonization area. However, in this subgroup the confidence intervals are very wide, confirming the scant visibility of the carbonization area in this subgroup of cases.
Despite that, Spearman rank correlation did not show any correlation between carbonization diameters, carbonization volumes and reference ablation parameters. We can conclude that even though technical parameters affect the final carbonized area achievable in a linear way, it is not possible to precisely predict dimensions and volume of the carbonized area by the operative parameters selected.
Our findings confirm that further elements beyond the technical parameters should be considered in the estimation of volume and extension of the overall ablated area. In particular, as previously proposed in literature, tissue-related parameters should be included in the pre-procedural planning to improve to ablation zone prediction [14]. In fact, if we rely only on technical parameters, the impact of further additional underlying mechanism potentially affecting the final dimensions and volume of the ablated area might otherwise be underestimated [14, 16].
To our knowledge, the influence of the ablative technical parameters on carbonized area dimensions has not been evaluated in literature so far, as well as the prediction of the final carbonization volume by the manufacturer reference values. Even if the amount of carbonization cannot be completely estimated by the ablation setting, the demonstration of the existence of a strong correlation between carbonization and necrosis represents an unprecedented element to take into account when planning an ablative procedure and which may lead to further research and clinical application. In fact, carbonization represents a peculiar feature of MW ablation and its assessment at imaging follow-up may be employed to visually monitor in real-time conditions the neoplastic tissue undergoing carbonization and to actively obtain a qualitative feedback of the treatment efficacy.
However, further investigations are recommended to improve the understanding of thermal and mechanical properties of tissues undergoing MW ablation, especially above 100 C [21]. In particular, the impact of the reflection index on the overall energy deployed should be taken into account when evaluating ablated tissue [14]. The reflection index, or reflection coefficient, mirrors the amount of the energy which reaches the antenna but is not transferred to the target due to the impedance mismatch at the interface between the tissue and the antenna itself [14, 25]. A low reflection coefficient determines a more efficient transfer of power from the antenna into the tissue [27, 40]. However, during ablation, tissue properties substantially change and so does the reflection coefficient, with consequent modification of the overall energy deployed to the tissue [27] and variability of ablation zone dimensions.
In addition, it is important to notice that ablated tissues significantly shrink on immediate post-ablation images and carbonisation highly contributes to tissue shrinkage during MW ablation [21, 37, 38]; therefore, the impact of tissue contraction as well as of the temporary expansion phenomena observed during the very first minutes of the ablation should be considered in order to obtain more consistent and predictable results [16, 21, 30].
Moreover, as previously proposed, a standardized way to consistently measure the extension of the carbonized tissue should be developed [21]. In this context, a considerable support could be represented by the employment of Dual-Energy CT (DECT) in the evaluation of the carbonized area after MW ablation. In fact, DECT is able to improve tissue characterization and provide more precise information about material composition due to the higher contrast-to-noise ratio (CNR) [41, 42]. Paul et al investigated temperature changes in ex-vivo porcine liver during MW ablation using DECT image data, concluding that DECT image datasets provided better
thermal sensitivity, visibility and lesion detection than Single-Energy CT (SECT) [39]. If these results will be confirmed even for the evaluation of the carbonized area, then DECT employment could potentially increase carbonization detection, especially in those cases where its visual conspicuity is not sufficient to ensure objective and reliable measurements. In adjunction, further benefit may derive from the development of dedicated Computer Aided Detection (CAD) software for the automatic detection and volume assessment of the carbonized area.
Our study has some limitations apart from its retrospective nature and the presence of both primary and metastatic liver lesions in the study population: in particular, different CT scanners have been employed to measure ablated and carbonized dimensions, and their volumes were approximated using the ellipsoid formula. In addition, measurements and carbonisation conspicuity assessment was performed by a single operator and the contribution of the shrinkage phenomenon to the final dimension of ablated areas was not considered. The equipment employed was from a single manufacturer and the TE energy deposited in tissues was estimated based on manufacturer-determined performance parameters, and reflectivity values were not available for the entire population. Finally, the use of 14- gauge and 16-gauge applicators may have confounded the results.
CONCLUSIONS
Carbonization represents a peculiar feature of MW ablation attributable to the higher temperatures reached in the treated lesion respect to other ablative techniques. In our experience, even if it was not possible to precisely predict dimensions and volume of the carbonized area by the operative parameters selected, a strong relationship between ablation and carbonization diameters and volumes was found. To our knowledge, the relation between the extension of the carbonization and the overall coagulated zone has not been proved before. Our results might suggest that carbonization could represent an indirect marker of the overall tumoral tissue undergoing thermal ablation by MW. Therefore, the identification of carbonization at imaging may represent a way to monitor the ablative procedure and to obtain a qualitative feedback of the treatment efficacy.
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