**1. Introduction**

Open surgery generally offers the best long-term survival rates for colorectal liver metastases (CRLM); with minimally invasive techniques becoming more common [1]. Magnetic resonance guided high intensity focused ultrasound (MRgHIFU) is noninvasive and non-ionizing, allowing for reduced treatment morbidity. At least one system for ultrasound guided focused ultrasound (USgFUS) ablation has been approved within the European Union for primary and secondary hepatic tumors [2].

Although, liver metastases are more common than primary liver tumors, most focused ultrasound studies report outcomes for primary hepatocellular carcinoma (HCC). The use of MRgHIFU for both primary and secondary hepatobiliary tumors is still awaiting certification and has not yet been reported in randomized controlled trials for CRLM or HCC [3]. Discussed here are the focused ultrasound (FUS) physics, the principles of MRI for liver metastases, analysis of the standard treatment approaches for CRLM, and previous studies involving ablation of liver tumors with USgFUS and MRgHIFU.

In 2019, cancer was reported to be the second leading cause of death, globally; amounting to approximately 1 in 6 deaths, worldwide [4]. The primary cause was due to exogenous factors resulting in genetic mutations and amounts to about 90% of reported cases [5]. P53 mutations in tumor suppressor genes are estimated in about 50% of cancers and RAS gene mutations of proto-oncogenes are estimated in about 30% of cancers. Tobacco use is thought to account for the majority of all cancer deaths. This is followed by high body mass index, alcohol use, and malnutrition [5].

HCC is the most common primary liver tumor type. There were approximately 906,000 new primary liver cancer cases in 2020, of which 75–85% were HCC, arriving at approximately 679,500–770,100 new HCC cases [6]. The most prevalent underlying conditions for HCC are Hepatitis-B virus, Hepatitis-C virus, and liver cirrhosis [7, 8]. Primary liver tumor treatment depends on history and staging. If HCC results from decompensated liver cirrhosis, surgical resection is not recommended. These patients do have the option of total liver transplant with 5-year survival rates of about 60–70%. Curative treatment options for late-stage diagnosis or recurrence is rare [8–10]. For HCC, the 10-year survival rate after surgical resection is approximately 25% [11]. However, liver transplant often offers much better outcomes than surgery for HCC. With liver transplant for patients meeting the Milan criteria, 5-year survival rates are near 70%, with less than 10% recurrence rates [11–13]. Liver transplant for HCC constitutes about 25% of liver transplants in the USA and about 40% of liver transplants in Europe [14].

CRLM is the most common form of secondary liver tumor [15]. CRLM occurs in about one-third to one-half of adult CRC cases and the liver metastases is the cause of death in about two-thirds of these patients [16]. In 2020, there were approximately 1.9 million new cases of CRC, of which it might be expected that 633,333–950,000 developed liver metastases [6]. Diagnostic radiologists have listed secondary liver tumor sites at 18–40 times more frequent than primary liver tumors, as the condition often presents with multiple metastases [17]. Historically, CRLM was deemed incurable with untreated 5-year survival rates of less than 2% [18]. Survival rates of patients with distant secondary metastatic tumors can be improved with surgical treatment and systemic chemotherapy [8, 19, 20]. Pediatric liver metastasis is more often secondary to Wilms' tumors or neuroblastomas rather than CRC [21, 22]. About 15% of adult patients exhibit liver metastasis at initial CRC diagnosis [23] and about 70% develop CRLM [2]. Approximately 60% of CRC deaths result from liver metastases [23, 24]. The standard treatment for CRLM is liver resection and is largely considered the best option for long-term curative potential [1, 8, 25, 26], with about a 40% survival rate after 5 years [2, 8, 23, 27], about a 24% survival rate after 10 years [2, 28], about a 20% cure rate [28], and a median survival rate of approximately 30 months [29]. However, for both HCC and CRLM, surgical eligibility is only 20–25% [2]. Liver transplant for CRLM has given good results in recent clinical trials when using tighter inclusion criteria and molecular profiling [30–32], although has historically given dismal survival rates, with high incidence of recurrence, survival rates only marginally better than systemic chemotherapy, and is not a primary option in

standard treatment algorithms [1, 33]. Hence, CRLM has an additional treatment difficulty, compared to HCC, because liver transplant does not generally provide long term survival.
