MR Linac: The Future of Targeted Radiotherapy
Andreas Wetscherek1
1The Institute of Cancer Research, London, United Kingdom

Synopsis

Keywords: Cross-organ: Cancer, Physics & Engineering: Interventional

Hybrid MR-Linac systems enable imaging of the soft-tissue anatomy at the time of radiation treatment. While staff numbers and durations of individual treatment fractions are currently higher than for treatments on standard linear accelerators, replanning on daily images can reduce the required hospital visits for some anatomies and clinical trials exploring safe dose escalation to overcome resistance become possible. Real-time guidance of the treatment beam with MRI and the use of MRI-derived biomarkers for response assessment and treatment adaptation are active research areas. To unleash the full potential of MR-Linacs, further advances in both MRI and treatment planning are required.

Radiotherapy fundamentals

Radiotherapy (RT) has been used in the treatment of cancer patients for over 100 years. It uses ionizing radiation to damage the DNA of cancer cells with the aim of inducing cell death. RT is part of the treatment for one in two cancer patients, where the most used form of radiation are high-energy X-rays from a linear accelerator. Treatments are typically split over several fractions (treatment days) and delivered based on a treatment plan that is calculated on attenuation maps derived from CT images. The goal of radiotherapy treatment planning is to deliver the prescribed dose to the target volume while adjusting the treatment beam angles and shapes (using multi-leaf collimators) to minimize the dose to normal tissue. This is achieved by tailored treatment planning software, which can take the characteristics of the treatment system into account. For some anatomies, a radio-sensitive organ-at-risk (OAR) close to the tumor can limit the dose that can be safely delivered to the target, especially when large treatment margins need to be applied to account for respiratory motion.

Challenges of conventional radiotherapy

Depending on the healthcare system and hospital resources there can be significant time (up to several weeks) between the MRI and CT scans used for RT planning and the actual treatment. During this time, changes in the patient anatomy, such as weight loss or changes in tumor size can occur; often the patients receive chemotherapy or immunotherapy in addition to RT. Onboard imaging on standard linear accelerators is typically available in the form of cone-beam CT (CBCT), which has limited soft-tissue contrast. In many cases only the bony anatomy is clearly visible and day-to-day variations in the location of soft tissue structures, for example related to the filling of hollow organs such as bladder, bowel and rectum are not visible at the time of treatment. To cope with the uncertainty regarding the exact anatomical configuration and to balance the need of maintaining coverage of the tumor with the prescribed dose against the risk of side-effect from irradiating adjacent radiosensitive structures, two main strategies are employed: First, the total dose is split into several fractions, delivered on different days, leveraging the better repair mechanisms of normal tissue compared to most tumors. Second, treatment margins are used to ensure coverage of the whole clinical target volume, resulting in the planning target volume (PTV).

From MR-guided radiotherapy to MR-Linac

First approaches to MR-guided radiotherapy were based on transferring the patient using a shuttle solution between a close-by MRI scanner and the linear accelerator for radiotherapy treatment. This approach leverages the excellent soft tissue contrast [1] of MRI to image the patient anatomy in treatment position just before treatment. A hybrid MR-Linac system removes the need for transporting the patient between imaging and treatment and furthermore enables real-time imaging during the delivery of the treatment. This can be used to account for respiratory motion during treatment, for example by tracking the tumor with the treatment beam [2]. Currently there are three main systems that received FDA clearance, ranging in field strength from 0.35 to 1.5T, which differ regarding the integration of MR and RT functions, for example in terms of the orientation of treatment beam and main magnetic field, open vs closed bore and regarding the exact specifications of the imaging gradients [3]. Novel commissioning experiments, which take the hybrid nature of MR-Linacs into account, were developed in multi-center efforts for the 1.5T system [4] and compared for the 0.35T system [5]. Extending the concept of MR-guidance to proton therapy is an active area of research [6]. Using an MRI system with a permanent 0.22T magnet at a research beamline it was possible to visualize the proton beam’s dose signature on time-of-flight MR images in a water phantom [7].

Clinical benefits of MR-guided radiotherapy treatments

MR-guided radiotherapy could add value over conventional radiotherapy, either by improving outcomes for patients, by potentially reducing the burden on healthcare systems or by enabling novel radiotherapy treatments. Many cancer treatments could benefit from MR-Linac treatments, some examples include head and neck cancer [8], liver cancer [9] and pancreatic cancer [10]. One approach to dose-escalated MR-guided radiotherapy is to maximize the dose delivered to the tumor for each fraction, while maintaining safe dose-levels for radiosensitive organs, such as the duodenum, for the anatomical configuration of the day. This led to improved overall survival and less grade 3+ gastrointestinal toxicity in a cohort of 44 inoperable pancreatic cancer when delivering high dose compared to standard dose [11]. Prostate cancer patients might benefit from delivering a dose boost to the dominant intraprostatic lesion, while the online imaging of MR-guided RT could allow for sparing of functional structures including the neurovascular bundle and the penile bulb. Currently trials are ongoing on both the 0.35 T and the 1.5 T system to evaluate ultra-hypofractionated radiotherapy, delivering treatment in only 2 fractions [12], which could reduce the burden on patients and clinical resources. Treatment of non-cancerous conditions with radiotherapy is also possible on MR-Linac systems. In particular, cardiac radioablation of ventricular tachycardia was demonstrated on the 0.35 T system [13] and the feasibility of physiology-based RT beam gating for cardiac radioablation based on electrocardiograms and MRI was demonstrated on the 1.5 T system [14].

Challenges of MR-Linac treatments

While a longitudinal study of MR imaging QA on the 1.5T system found good stability of the imaging properties for individual systems, noticeable differences in terms of field homogeneity and its dependency on gantry rotation between different installations were found [15]. In first designs of the 0.35T system, B0 eddy currents were out of specification for most gantry angles [16], but a redesign of the waveguide reduced the eddy currents and associated imaging isocenter shifts [17]. Dynamic B0 shimming techniques could reduce effects of gantry rotation [4, 16] and could play a role in enabling biologically adaptive radiotherapy. While hypofractionation reduces the number of required hospital visits, the individual treatments become longer and slow anatomical changes, such as organ drifts, for example related to the slow filling of hollow organs, become relevant. One approach to account for these drifts is the use of fast volumetric imaging [18].

The Future of MR-guided radiotherapy

While in practice, abdominal compression is often used to reduce the amount of respiratory motion in the abdomen, research on real-time imaging for image guidance is ongoing [19]. Respiratory-correlated and time-resolved 4D-MRI [20] are explored in the MR-Linac context, either based on stack-of-stars acquisitions [21] or slice-selective excitations [22]. Reconstruction times for 4D-MRI can be reduced by using neural networks [23, 24] and by exploiting advances in computing hardware [25]. Current proposals for volumetric real-time imaging often consist of a training phase and a real-time phase, either based on fast image registration [26] or a motion signature [21, 27]. An open question is how to correctly accumulate the dose delivered to targets that change in volume or deform when undergoing physiological motion [28, 29]. Another area of active research and one of the motivations for MR-guided radiotherapy is the idea of using MRI-derived biomarkers for biologically adaptive radiotherapy, where early detection of response, resistance or toxicity could inform treatment adaptation [30, 31]. Different quantitative MRI techniques have been implemented on MR-Linacs in research settings, including chemical exchange saturation transfer MRI [32] and magnetic resonance fingerprinting [33, 34]. MR relaxometry [35] could further be employed to detect hypoxia, which is associated with treatment resistance. In this context, the use of oxygen-enhanced MRI was translated to an MR-Linac for patients with head and neck cancer [36]. Another active area of research is diffusion-weighted MRI on MR-Linacs, focusing on measurements of the apparent diffusion coefficient and intravoxel incoherent motion parameters [37]. An recent overview of studies investigating clinical validation of quantitative MRI for biologically adaptive radiotherapy can be found in [30]. To meet the requirements of geometric accuracy, TSE-based diffusion-weighted sequences have been explored, both at 0.35 T [38] and 1.5 T [39]. Further guidance regarding the future of MRI in radiotherapy and MR-guided radiation therapy can be found in [40] and [29], respectively.

Acknowledgements

No acknowledgement found.

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Proc. Intl. Soc. Mag. Reson. Med. 32 (2024)