Microwave ablation of multifocal primary liver cancer guided by real-time 3.0T MRI

Abstract Objective To investigate the feasibility and efficacy of real-time 3.0 T magnetic resonance imaging (MRI) guided percutaneous microwave ablation (MWA) in the treatment of multifocal liver cancer. Methods A total of 76 lesions in 26 patients with multifocal liver cancer who underwent 3.0 T MRI-guided microwave ablation in our hospital from April 2020 to April 2022 were retrospectively analyzed. The technical success rate, average operation time, average ablation time, and complications were evaluated. The upper abdomen was reviewed by pre- and post-contrast enhanced MRI scan every 1 months after the operation. The short-term curative effect was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria (2020 version), and the local control rate was calculated. Results All 76 lesions were successfully operated. The technical success rate was 100%, the average operation time was 103.58 ± 18.57 min, the average ablation time of a single lesion was 11.00 ± 4.05 min, and the average ablation power was 43.03 ± 4.45 W. There were no serious complications such as massive bleeding, liver failure, and infection after the operation, except in one case with a small amount of pleural effusion and one case with right upper abdominal pain. The average follow-up time was 13.88 ± 6.62 months. One patient died due to liver failure, and one lesion developed a local recurrence. The local control rate was 98.7%. Conclusions MWA of multifocal liver cancer guided by real-time 3.0 T MRI is a safe and feasible technique and has excellent short-term efficacy.


Introduction
Liver cancer is a highly malignant tumor and a common carcinoma.Its morbidity and mortality are on the rise globally.According to the estimation of the International Agency for Research on Cancer (IARC), about 905,000 people suffered from liver cancer in 2020, causing 830,000 deaths worldwide [1].Surgical resection is considered the preferred method for the treatment of primary liver cancer [2].Most multifocal liver cancers have tumors located in different liver segments.Therefore, the surgical resection rate of such tumors is relatively low, and treatment methods such as transcatheter arterial chemoembolization (TACE), local ablation, or liver transplantation are mostly used [3][4][5].However, the longterm efficacy of TACE is unsatisfactory, especially for multifocal liver cancer [6].Liver transplantation is difficult to popularize due to the shortage of donor organs, high cost, and life-long immune maintenance of recipients.With the development of modern imaging, local ablation is increasingly used for clinical cancer treatment.
Percutaneous ablation techniques, including microwave ablation (MWA) and radiofrequency ablation (RFA), have become important minimally invasive treatment options for liver cancer.Microwave ablation is a form of thermal ablation for the interventional treatment of cancer.Compared with RFA, microwave ablation has the advantages of high thermal efficiency, fast heating rate, and less influence from the 'heat sink effect' [7].At present, the most widely used image-guiding devices include computed tomography (CT), ultrasound (US), etc. CT-guided intervention is easy to affect the intraoperative display of small lesions due to metal material artifacts, and there is some deviation in the determination of the ablation boundary of small lesions equal or less than 1.0 cm.Although sonographically guided percutaneous microwave ablation proved to be safe, fast and effective for the treatment of hepatocellular carcinoma, ultrasound guidance is easily interfered with by various factors such as gas, bone, and liver movement, and the gasification phenomenon generated during thermal ablation may affect the evaluation of the ablation area [8,9].
Magnetic resonance imaging (MRI) guidance can give full play to its advantages of high soft tissue resolution, multiplane and multi-parameter imaging, clearly showing the ablation focus and range without ionizing radiation.Currently, MRI-guided local ablation for the treatment of single hepatocellular carcinoma has been reported [10][11][12], but mostly done under the guidance of a 1.0 T or 1.5 T MRI scanner.There were few reports on high-field-strength MRIguided ablation therapy.This investigation aimed to evaluate the feasibility and effectiveness of real-time 3.0 T MRI-guided percutaneous microwave ablation in the treatment of multifocal hepatocellular carcinoma.

Patients
The clinical data of 26 patients with multifocal liver cancer who underwent MRI-guided microwave ablation in our hospital from April 2020 to April 2022 was retrospectively collected.26 patients (24 males and 2 females) with a total of 76 lesions were finally confirmed according to the inclusion and exclusion criteria.The inclusion and exclusion criteria were as follows: Inclusion criteria

Equipment
3.0T MR scanner (Discovery MR750W, GEHC, Waukesha, WI, USA) and 8-channel body coil with operating holes were used for scanning.This is a modified coil, which is designed with the actual needs of the interventional operation fully considered.The coil is designed to have a multi-hole appearance with four holes and 12 channels.The size of the holes is ensured to be sufficient for interventional operations (Supplementary Figure 1).MRI-compatible microwave therapy apparatus was used in this investigation, and the size of the microwave ablation needle was 1.8 mm Â 150 mm (model ECO-100AI13, ECO medical, Nanjing, China, made of ceramic, maximum withstand power: 55 W).

Preoperative preparation
Within one week before surgery, all patients underwent preand post-contrast enhanced MRI scan of the upper abdomen to determine the location, size and number of lesions for ablation; some patients underwent enhanced scans with liver-specific MRI contrast agent (EOB-DTPA) to identify hidden or atypical lesions.Typical target signs were sought during the operation.On T1WI, the central primary lesion was hypointense.On T2WI, the ablation lesion shows low signal intensity surrounded by a thin layer of hyperintense inflammatory area.Routine blood tests, total biochemical items, liver and kidney function, and tumor markers (AFP, CEA, CA19-9) were tested preoperatively.

Procedure of puncture and treatment
Fasting for 4-6 h before surgery, venous access was established for the patient, and blood pressure, heartbeat and respiratory rate were monitored.All patients underwent this procedure under local anesthesia.The cod liver oil matrix was placed on the skin surface, and a non-enhanced MR scan was performed to determine the puncture path.Important structures such as blood vessels and bile ducts were avoided as much as possible.Non-enhanced MR scan was repeated to determine the optimal puncture path, the coil was wrapped with a sterile surgical towel, and the puncture point was sterilized with iodophor and local infiltration anesthesia with 2% lidocaine.Under the real-time guidance of MRI, a microwave ablation needle was gradually inserted into the center of the tumor using a 'step-by-step method' [15].Multiple scans were performed during the puncture process, maintaining the scan level parallel to the direction of needle insertion, to ensure that the needle was inserted in the correct direction, and continuously adjusting the position of the microwave ablation needle until the tip of the ablation needle exceeded the distal end of the tumor by 0.5-1 cm, which is regarded as a puncture success.Only two patients received 2 ablation needles at the same time, and the size of the tumors are more than 4 cm.Connect cables and water loops to MWA equipment.Ablation was performed at 35-50 W for 10-30 min until the ablation area covered the entire lesion and was 0.5-1 cm beyond the edge.Repeated intraoperative MRI scans (T2WI, LAVA-Flex) were performed to evaluate ablation effects and complications.If the target lesion is not completely covered by the ablation zone with T1 high signal or T2 low signal, continue ablation or adjust the needle direction, until the high signal ring on the LAVA-Flex sequence covers the central low signal tumor and more than 0.5 cm beyond in the periphery (called the target sign) [16].Then the MWA was closed, the ablation needle was withdrawn along the puncture path, and the skin wound was protected with a sterile applicator.After the operation, the patient was instructed to stay in the inpatient department and receive liver protection and acid suppression therapy (Protect liver: intravenous drip magnesium isoglycyrrhizinate injection 150 mg þ 0.5% glucose injection 250 ml; Acid suppression: esomeprazole sodium for intravenous infusion 40 mg þ 0.9% sodium chloride injection 100 ml.) for three days.

Follow up
The patients were reexamined by pre-and post-contrast enhanced MR scans every 1 months after the operation, and the short-term curative effect was evaluated according to the modified mRECIST criteria (2020 version) [17], and the levels of tumor markers (AFP, CEA, CA19-9) were dynamically monitored.MRI images were evaluated by two radiologists with more than 10 years of experience in abdominal magnetic resonance imaging.All these 26 cases were followed up until April 2022.
Complications were recorded for all patients during follow-up according to the Society of Interventional Radiology (SIR) clinical practice guideline classification of complications [18].

Data collection
The research is a retrospective single-center review of MRguided microwave ablation at 3.0 T. Two research assistants independently collected and reviewed retrospective data for this study.The collected data includes the number of lesions, the size of the tumor, the operation time (from the beginning to the end of radiofrequency ablation), the working time of the microwave therapy apparatus after the puncture needle enters the tumor center (the ablation time), and the postoperative complications of the patient (Biliary fistula, Pulmonary embolism, Transfer, Pain, Pleural effusion).

Statistical analysis
All data were statistically analyzed using SPSS 21.0.Measurement data were expressed as mean ± standard deviation (means ± SD) when they conformed to normal distribution.Otherwise, variables with skewed distributions were expressed as median (Q1, Q3).The count data were expressed as the number of cases/percentage (n/%).

Patient characteristics
Of the 26 patients in this investigation, 13 received ablation without surgery resection, and 13 received ablation after recurrence after surgical resection or TACE.The age ranged from 39.0 to 77.0 years, with an average age of 60.12 ± 8.84 years.The number of lesions in a single patient was 2-6, the diameter of the lesions was 0.7-4.9cm, and the average diameter was 1.81 ± 0.94 cm (Shown in Table 2).

Technical success rate and complications
A total of 76 tumor lesions in 26 patients completed the MWA successfully, with a technical success rate of 100%.Two lesions were treated under two ablation needles at the same time, and the remaining lesions were treated under one ablation needle.During the follow-up time of 13.88 ± 6.62 months (range from 1 to 24 months), a small amount of pleural effusion (about 350 ml) (SIR grade B) developed in 1 case, and severe right upper abdominal pain (SIR grade B) developed in another case.There were no serious complications such as hemorrhage, liver failure, infection, and diaphragm perforation.The overall postoperative complication rate was 7.7% (2/26) (Shown in Table 3).

Therapeutic effect
The average operation time was 103.58 ± 18.57 min (range from 78 to 140 min), the average ablation time of a single lesion was 11.00 ± 4.05 min (range from 5 to 20 min).As of the follow-up date, 75 lesions achieved complete ablation (CA), the complete ablation rate reached 98.7% (75/76).One patient had a local recurrence, and one patient died of liver failure.MRI findings were shown in Figures 1-3.

Discussion
Microwave ablation therapy has been widely used in the treatment of liver cancer, and the curative effect of ablation therapy for early-stage liver cancer is similar to that of surgery resection [19].At the same time, it has the advantages of less damage to liver function and quick post-ablation recovery.Microwave ablation can be used as a first-line treatment strategy for patients with early-stage liver cancer, especially for multifocal liver cancer, which is difficult to surgically resect [20].Compared with radiofrequency ablation (RFA), microwave ablation (MWA) has the advantages of a fast heating rate, high ablation efficiency, and short time required, and is less affected by the 'heat sink effect' and metal substances in the body [21].Studies have shown that the long-term survival and prognosis of patients with liver cancer are related to the number of ablation treatments per lesion [22].Therefore, in ablation therapy, image-guided equipment is required to have the capabilities of precise preoperative positioning, intraoperative dynamic monitoring, and accurate postoperative evaluation, and this is especially true for the treatment of multifocal liver cancer.
Studies have shown that the overall sensitivity of ultrasound, CT, and MRI for Liver cancer is about 32-63%, 66-79%, and 84-90%, respectively [23].For small liver cancers with a diameter of 2 cm, the sensitivity of Gd-EOB-DTPAenhanced MRI can reach 90%-96% [24].The advantages such as high soft tissue resolution, the capacity of multiplane imaging and lack of ionizing radiation make MRI very suitable for guiding ablation therapy.In addition, MRI-guided microwave ablation can realize any direction of needle insertion.The needle can be accurately positioned and free from bone and gas artifacts.Compared with low-field MRI, 3.0 T has a higher signal-to-noise ratio, and the detection ability of small lesions is greatly improved.In this study, 16 lesions were less than 1.0 cm in size, it is questionable whether these small lesions can be clearly displayed on 1.5 or 1.0 T MRI imaging.At the same time, the scanning speed of 3.0 T is faster, and the contrast of T2WI is also better.3.0 T MRI is more sensitive to changes in tissue temperature.During the process of liver thermal ablation, the MRI signal changes immediately with changes in liver tissue temperature [25].Compared with CT, MRI can accurately display the ablation effect without a contrast agent in most cases [16].In our investigation, 20 patients underwent MRI guiding without contrast-enhanced scanning.The longer hepatobiliary phase time of liver-specific contrast agent also provides sufficient time to guide MWA to some occult lesions which can only be visualized clearly with Gd-EOB-DTPA enhanced MRI [26].'Hybrid US-MR I' can improve the quality of liver magnetic resonance (MR) images, reduce artifacts, and facilitate the visualization and localization of small lesions [27].Particularly, 'Real-Time Hybrid US-MR Imaging' has certain advantages over conventional respiratory-gated techniques for liver ablation guidance [27].However, this method requires US equipment and corresponding computer systems, which may not be readily available in the majority of medical institutions.Moreover, the procedure is relatively complex, and the additional equipment may potentially impact the workflow during treatment.Therefore, the clinical utility of this approach needs further validation.Multienergy CT contributes to the visualization of small intrahepatic lesions and helps to mitigate the influence of metal artifacts caused by ablation needles to a certain extent, presenting advantages over conventional CT [28].However, challenges still exist in the intraoperative and immediate postoperative assessment of treatment efficacy.Furthermore, as a high-end imaging device, Multienergy CT resources remain limited, making it less easily accessible for widespread use.
Of the 26 patients in this investigation, 13 received ablation without surgery resection, and 13 received ablation after recurrence after surgical resection or TACE.75 of the 76 lesions achieved complete ablation, with a local control rate of 98.7%.In previous studies, the studies on RFA or MWA in the treatment of primary liver cancer were mostly limited to small liver cancer (single tumor, diameter 5 cm; or 2-3 tumors, maximum diameter 3 cm) [10,11,29].In this study, there were 4 patients who had more than 3 intrahepatic tumors (4 tumors in 2 patients, 6 tumors in 2 patients), and all of them achieved a complete ablation under the guidance of MRI without any local residual and recurrence until the end of the follow-up period.Previous studies have found that the long-term efficacy of local thermal ablation is related to a variety of factors [20].Zhang S studied the efficacy and influencing factors of combined RFA with TACE treatment for primary liver cancer, and found that tumor diameter !3 cm, incomplete capsule, intrahepatic spread, and tumor adjacent to large blood vessels are risk factors for recurrence after treatment [30].In addition to these factors, real-time assessment of therapeutic response during MWA is critical to determine the effectiveness of the procedure and whether the tumor tissue is completely inactivated.Ultrasound-guided ablation is prone to generate air bubbles, which affects the evaluation of the treatment effect.The presence of puncture needle artifact under CT guidance can also impact the determination of the ablation boundary by necessitating multiple ablation sessions [31] MRI allows realtime monitoring of treatment response without contrastenhanced scans, and has the capability to show important structures adjacent to the lesions, such as bile ducts or blood vessels.Many studies have shown that MRI-guided MWA has better tumor control rates and fewer complications with MRI-guided MWA [32][33][34].In this investigation, ablation of each lesion was essentially within 2 h, usually not done in a single procedure, and often require the operator to evaluate the appearance of the lesion on the MRI images repeatedly during the operation until the typical target sign appeared.On T1WI, the Foci of the central prototumor showed low signal intensity, and the surrounding normal liver tissue showed a high signal intensity ring.On T2WI, the ablation lesion showed low signal intensity, surrounded by a thin layer of the high signal inflammatory zone.In this way, the   surrounding blood vessels and liver tissues were protected well, the incidence of complications was low, and all patients achieved a grade of B in the adverse events of SIR.During the follow-up period, local recurrence was found in 1 lesion located in the right lobe of the liver near the top of the diaphragm, and about 2.0 cm diameter.The reason for the local recurrence may be related to its proximity to the right hepatic vein, and the 'heat deposition' effect leads to incomplete ablation.The patient subsequently received MR-guided I 125 seed implantation, and no signs of local tumor recurrence were found during the 12-month follow-up period.
Compared with other guiding methods such as DSA, ultrasound, and CT, MRI also has some disadvantages.First, the scanning time of MRI is long and the noise is high, and some elderly patients may have problems with irritability during the operation and difficulty adhering to it.Second, poor image quality may inevitably affect the operator's evaluation of efficacy in the presence of poor respiratory fit.Besides, compared with ultrasound and CT, the cost of surgery and MR-compatible interventional equipment is relatively higher.

Limitations
There are some limitations to this investigation: First, this is a single-center retrospective investigation with a small sample size and a short follow-up time.The long-term efficacy and prognosis of MWA in the treatment of multifocal liver cancer still needs to investigated.And due to the limited number of cases, the exploration of recurrence-related risk factors could not be carried out.Second, this investigation lacks a control group, especially for the comparison with the efficacy of CT or ultrasound-guided MWA.Besides, because all 26 patients in this investigation were guided under local anesthesia, and considering the financial burden of patients, most lesions were treated with only 1 ablation needle, which may lead to prolonged operation time.When the operation time is longer, some patients may have difficulty in cooperating during the operation.

Conclusion
Real-time 3.0 T MRI-guided microwave ablation for the treatment of multifocal liver cancer is feasible and safe, with excellent short-term efficacy and few complications.However, further research with larger sample size and longterm follow-up may be needed to support the application of this method.

Disclosure statement
No potential conflict of interest was reported by the author(s).

Figure 2 .
Figure 2. Intraoperative imaging: the microwave ablation needle showed low signal in all sequences and was inserted into the center of the tumor step by step (a,b).the scanning equipment was Ge MR750W with the following parameters: FOV ¼ 40 cm, phase FOV ¼ 0.8, and layer thickness 5.0 mm.Matrix ¼ 256 Ã 192, NEX ¼ 1, bandwidth ¼ 142.8, flip angle ¼ 15.
SIR: Society of Interventional Radiology.