MRI-guided Pelvic Radiation Therapy: A Primer for Radiologists.

Radiation therapy (RT) is a core pillar of oncologic treatment, and half of all patients with cancer receive this therapy as a curative or palliative treatment. The recent integration of MRI into the RT workflow has led to the advent of MRI-guided RT (MRIgRT). Using MRI rather than CT has clear advantages for guiding RT to pelvic tumors, including superior soft-tissue contrast, improved organ motion visualization, and the potential to image tumor phenotypic characteristics to identify the most aggressive or treatment-resistant areas, which can be targeted with a more focal higher radiation dose. Radiologists should be familiar with the potential uses of MRI in planning pelvic RT; the various RT techniques used, such as brachytherapy and external beam RT; and the impact of MRIgRT on treatment paradigms. Current clinical experience with and the evidence base for MRIgRT in the settings of prostate, cervical, and bladder cancer are discussed, and examples of treated cases are illustrated. In addition, the benefits of MRIgRT, such as real-time online adaptation of RT (during treatment) and interfraction and/or intrafraction adaptation to organ motion, as well as how MRIgRT can decrease toxic effects and improve oncologic outcomes, are highlighted. MRIgRT is particularly beneficial for treating mobile pelvic structures, and real-time adaptive RT for tumors can be achieved by using advanced MRI-guided linear accelerator systems to spare organs at risk. Future opportunities for development of biologically driven adapted RT with use of functional MRI sequences and radiogenomic approaches also are outlined. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

First-in-human technique translation of oxygen-enhanced MRI to an MR Linac system in patients with head and neck cancer.

BACKGROUND AND PURPOSE: Tumour hypoxia is prognostic in head and neck cancer (HNC), associated with poor loco-regional control, poor survival and treatment resistance. The advent of hybrid MRI - radiotherapy linear accelerator or 'MR Linac' systems - could permit imaging for treatment adaptation based on hypoxic status. We sought to develop oxygen-enhanced MRI (OE-MRI) in HNC and translate the technique onto an MR Linac system. MATERIALS AND METHODS: MRI sequences were developed in phantoms and 15 healthy participants. Next, 14 HNC patients (with 21 primary or local nodal tumours) were evaluated. Baseline tissue longitudinal relaxation time (T1) was measured alongside the change in 1/T1 (termed ΔR1) between air and oxygen gas breathing phases. We compared results from 1.5 T diagnostic MR and MR Linac systems. RESULTS: Baseline T1 had excellent repeatability in phantoms, healthy participants and patients on both systems. Cohort nasal concha oxygen-induced ΔR1 significantly increased (p < 0.0001) in healthy participants demonstrating OE-MRI feasibility. ΔR1 repeatability coefficients (RC) were 0.023-0.040 s-1 across both MR systems. The tumour ΔR1 RC was 0.013 s-1 and the within-subject coefficient of variation (wCV) was 25% on the diagnostic MR. Tumour ΔR1 RC was 0.020 s-1 and wCV was 33% on the MR Linac. ΔR1 magnitude and time-course trends were similar on both systems. CONCLUSION: We demonstrate first-in-human translation of volumetric, dynamic OE-MRI onto an MR Linac system, yielding repeatable hypoxia biomarkers. Data were equivalent on the diagnostic MR and MR Linac systems. OE-MRI has potential to guide future clinical trials of biology guided adaptive radiotherapy.

Reirradiation Options for Previously Irradiated Prostate cancer (RO-PIP): Feasibility study investigating toxicity outcomes following reirradiation with stereotactic body radiotherapy (SBRT) versus high-dose-rate brachytherapy (HDR-BT).

INTRODUCTION: Radiotherapy is the most common curative treatment for non-metastatic prostate cancer; however, up to 13% of patients will develop local recurrence within 10 years. Patients can undergo further and potentially curative treatment including salvage surgery, brachytherapy (BT), external beam radiotherapy, high-intensity focused ultrasound and cryotherapy. Systematic review shows that high-dose-rate (HDR) BT and stereotactic body radiotherapy (SBRT) have the best outcomes in terms of biochemical control and lowest side effects. The reirradiation options for previously irradiated prostate cancer (RO-PIP) trial aims to determine the feasibility of recruitment to a trial randomising patients to salvage HDR-BT or SBRT and provide prospective data on patient recorded toxicity outcomes that will inform a future phase III trial. METHODS AND ANALYSIS: The primary endpoint of the RO-PIP feasibility study is to evaluate the patient recruitment potential over 2 years to a trial randomising to either SBRT or HDR-BT for patients who develop local recurrence of prostate cancer following previous radiation therapy. The aim is to recruit 60 patients across 3 sites over 2 years and randomise 1:1 to SBRT or HDR-BT. Secondary objectives include recording clinician and patient-reported outcome measures to evaluate treatment-related toxicity. In addition, the study aims to identify potential imaging, genomic and proteomic biomarkers that are predictive of toxicity and outcome based on hypoxia status, a prognostic marker of prostate cancer. ETHICS AND DISSEMINATION: This study has been approved by the Yorkshire and The Humber-Bradford Leeds Research Ethics Committee (Reference: 21/YH/0305, IRAS: 297060, January 2022). The results will be presented in national and international conferences, published in peer-reviewed journals and will be communicated to relevant stakeholders. A plain English report will be shared with the study participants, patients' organisations and media. TRIAL REGISTRATION NUMBER: ISRCTN 12238218 (Amy Ackroyd NIHR CPMS Team).

To see or not to see: Evaluation of magnetic resonance imaging sequences for use in MR Linac-based radiotherapy treatment.

BACKGROUND/PURPOSE: This work evaluated the suitability of MR derived sequences for use in online adaptive RT workflows on a 1.5 Tesla (T) MR-Linear Accelerator (MR Linac). MATERIALS/METHODS: Non-patient volunteers were recruited to an ethics approved MR Linac imaging study. Participants attended 1-3 imaging sessions in which a combination of DIXON, 2D and 3D volumetric T1 and T2 weighted images were acquired axially, with volunteers positioned using immobilisation devices typical for radiotherapy to the anatomical region being scanned. Images from each session were appraised by three independent reviewers to determine optimal sequences over six anatomical regions: head and neck, female and male pelvis, thorax (lung), thorax (breast/chest wall) and abdomen. Site specific anatomical structures were graded by the perceived ability to accurately contour a typical organ at risk. Each structure was independently graded on a 4-point Likert scale as 'Very Clear', 'Clear', 'Unclear' or 'Not visible' by observers, consisting of radiographers (therapeutic and diagnostic) and clinicians. RESULTS: From July 2019 to September 2019, 18 non-patient volunteers underwent 24 imaging sessions in the following anatomical regions: head and neck (n=3), male pelvis (n=4), female pelvis (n=5), lung/oesophagus (n=5) abdomen (n=4) and chest wall/breast (n=3). T2 sequences were the most preferred for perceived ability to contour anatomy in both male and female pelvis. For all other sites T1 weighted DIXON sequences were most favourable. CONCLUSION: This study has determined the preferential sequence selection for organ visualisation, as a pre-requisite to our institution adopting MR-guided radiotherapy for a more diverse range of disease sites.

The impact of an educational tool in cervix image registration across three imaging modalities.

OBJECTIVES: Accurate image registration is vital in cervical cancer where changes in both planning target volume (PTV) and organs at risk (OARs) can make decisions regarding image registration complicated. This work aims to determine the impact of a dedicated educational tool compared with experience gained in MR-guided radiotherapy (MRgRT). METHODS: 10 therapeutic radiographers acted as observers and were split into two groups based on previous experience with MRgRT and Monaco treatment planning system. Three CBCT-CT, three MR-CT and two MR-MR registrations were completed per patient by each observer. Observers recorded translations, time to complete image registration and confidence. Data were collected in two phases; prior to and following the introduction of a cervix registration guide. RESULTS: No statistically significant differences were noted between imaging modalities. Each group was assessed independently pre- and post-education, no statistically significant differences were noted in either CBCT-CT or MR-CT imaging. Group 1 MR-MR imaging showed a statistically significant reduction in interobserver variability (p=0.04), in Group 2, the result was not statistically significant (p=0.06). Statistically significant increases in confidence were seen in all three modalities (p≤0.05). CONCLUSIONS: At The Christie NHS Foundation Trust, radiographers consistently registered images across three different imaging modalities regardless of their previous experience. The implementation of an image registration guide had limited impact on inter- and intraobserver variability. Radiographers' confidence showed statistically significant improvements following the use of the registration manual. ADVANCES IN KNOWLEDGE: This work helps evaluate training methods for novel roles that are developing in MRgRT.

The impact of gadolinium-based MR contrast on radiotherapy planning for oropharyngeal treatment on the MR Linac.

PURPOSE: Gadolinium-based contrast agents (GBCAs) may add value to magnetic resonance (MR)-only radiotherapy (RT) workflows including on hybrid machines such as the MR Linac. The impact of GBCAs on RT dose distributions however have not been well studied. This work used retrospective GBCA-enhanced datasets to assess the dosimetric effect of GBCAs on head and neck plans. METHODS: Ten patients with oropharyngeal squamous cell carcinoma receiving RT from November 2018 to April 2020 were included in this study. RT planning included contrast-enhanced computed tomography (CT) and MR scans. A contrast agent "contour" was defined by delineating GBCA-enhanced regions using an agreed window/level threshold, transferred to the planning CT and given a standardized electron density (ED) of 1.149 in the Monaco treatment planning system (Elekta AB). Four plans were per patient calculated and compared using two methods: (1) optimized without contrast (Plan A) then recalculated with ED (Plan B), and (2) optimized with contrast ED (Plan C) then without (Plan D). For target parameters minimum and maximum doses to 1cc of PTVs, D95 values, and percent dose differences were calculated. Dose differences for organs-at-risk (OARs) were calculated as a percentage of the clinical tolerance value. For the purposes of this study, ±2% over the whole treatment course was considered to be a clinically acceptable dose deviation. Wilcoxon-signed rank tests were used to determine any dose differences within and between the two methods of optimization and recalculation (p < 0.05). Pearson's correlations were used to establish the relationship between gadolinium uptake volume in a structure (i.e., proportion of structure covered by a density override) and the resulting dose difference. RESULTS: The median percent dose differences for key reportable dosimetric parameters between non-contrast and simulated contrast plans were <1.2% over all fractions over all patients for reportable target parameters (mean 0.34%, range 0.22%-1.02%). The percent dose differences for maximum dose to 1cc of both PTV1 and PTV2 were significantly different after application of density override (p < 0.05) but only in method 2 (Plan C vs. Plan D). For D95 PTV1, there was a statistically significant effect of density override (p < 0.01), however only in method 1 (Plan A vs. Plan B). There were no significant differences between calculation methods of the impact of contrast in most target parameters with the exception of D95 PTV1 (p < 0.01) and for D95 PTV2 (p < 0.05). The median percent dose differences for reportable OAR parameters as a percentage of clinical planning tolerances were <2.0% over a full treatment course (mean 0.65%, range 0.27%-1.62%). There were no significant differences in dose to OARs within or between methods for contrast impact assessment. CONCLUSIONS: Dose differences to targets and OARs in oropharyngeal cancer treatment due to the presence of GBCA were minimal, and this work suggests that prospective in vivo evaluations of impact may not be necessary in this clinical site. Accounting for GBCAs may not be needed in daily adaptive workflows on the MR Linac.

MRI and CBCT for lymph node identification and registration in patients with NSCLC undergoing radical radiotherapy.

PURPOSE: This study compared MRI to CBCT for the identification and registration of lymph nodes (LN) in patients with locally advanced (LA)-NSCLC, to assess the suitability of targeting LNs in future MR-image guided radiotherapy (MRgRT) workflows. METHOD: Radiotherapy radiographers carried out Visual Grading Analysis (VGA) assessment of image quality, LN registration and graded their confidence in registration for each of the 24 LNs on CBCT and two MR sequences, MR1 (T2w Turbo Spin Echo) and MR2 (T1w DIXON water only image). RESULTS: Pre-registration image quality assessment revealed MR1 and MR2 as significantly superior to CBCT in terms of image quality (p ≤ 0.01). No significant differences were noted in interobserver variability for LN registration between CBCT, MR1 and MR2. Observers were more confident in their MR registrations compared to their CBCT based LN registrations (p ≤ 0.02). SUMMARY: Interobserver setup correction variability was not found to be significantly different between CBCT and MR. Image quality and registration confidence were found to be superior for MRI sequences. This is a promising step towards MR-guided radiotherapy for the treatment of LA-NSCLC.

Initial Clinical Experience of MR-Guided Radiotherapy for Non-Small Cell Lung Cancer.

Curative-intent radiotherapy plays an integral role in the treatment of lung cancer and therefore improving its therapeutic index is vital. MR guided radiotherapy (MRgRT) systems are the latest technological advance which may help with achieving this aim. The majority of MRgRT treatments delivered to date have been stereotactic body radiation therapy (SBRT) based and include the treatment of (ultra-) central tumors. However, there is a move to also implement MRgRT as curative-intent treatment for patients with inoperable locally advanced NSCLC. This paper presents the initial clinical experience of using the two commercially available systems to date: the ViewRay MRIdian and Elekta Unity. The challenges and potential solutions associated with MRgRT in lung cancer will also be highlighted.

IPEM Topical Report: an international IPEM survey of MRI use for external beam radiotherapy treatment planning.

Introduction/Background. Despite growing interest in magnetic resonance imaging (MRI), integration in external beam radiotherapy (EBRT) treatment planning uptake varies globally. In order to understand the current international landscape of MRI in EBRT a survey has been performed in 11 countries. This work reports on differences and common themes identified.Methods. A multi-disciplinary Institute of Physics and Engineering in Medicine working party modified a survey previously used in the UK to understand current practice using MRI for EBRT treatment planning, investigate how MRI is currently used and managed as well as identify knowledge gaps. It was distributed electronically within 11 countries: Australia, Belgium, Denmark, Finland, France, Italy, the Netherlands, New Zealand, Sweden, the UK and the USA.Results. The survey response rate within the USA was <1% and hence these results omitted from the analysis. In the other 10 countries the survey had a median response rate of 77% per country. Direct MRI access, defined as either having a dedicated MRI scanner for radiotherapy (RT) or access to a radiology MRI scanner, varied between countries. France, Italy and the UK reported the lowest direct MRI access rates and all other countries reported direct access in ≥82% of centres. Whilst ≥83% of centres in Denmark and Sweden reported having dedicated MRI scanners for EBRT, all other countries reported ≤29%. Anatomical sites receiving MRI for EBRT varied between countries with brain, prostate, head and neck being most common. Commissioning and QA of image registration and MRI scanners varied greatly, as did MRI sequences performed, staffing models and training given to different staff groups. The lack of financial reimbursement for MR was a consistent barrier for MRI implementation for RT for all countries and MR access was a reported important barrier for all countries except Sweden and Denmark.Conclusion. No country has a comprehensive approach for MR in EBRT adoption and financial barriers are present worldwide. Variations between countries in practice, equipment, staffing models, training, QA and MRI sequences have been identified, and are likely to be due to differences in funding as well as a lack of consensus or guidelines in the literature. Access to dedicated MR for EBRT is limited in all but Sweden and Denmark, but in all countries there are financial challenges with ongoing per patient costs. Despite these challenges, significant interest exists in increasing MR guided EBRT planning over the next 5 years.

IPEM topical report: guidance on the use of MRI for external beam radiotherapy treatment planning.

This document gives guidance for multidisciplinary teams within institutions setting up and using an MRI-guided radiotherapy (RT) treatment planning service. It has been written by a multidisciplinary working group from the Institute of Physics and Engineering in Medicine (IPEM). Guidance has come from the experience of the institutions represented in the IPEM working group, in consultation with other institutions, and where appropriate references are given for any relevant legislation, other guidance documentation and information in the literature. Guidance is only given for MRI acquired for external beam RT treatment planning in a CT-based workflow, i.e. when MRI is acquired and registered to CT with the purpose of aiding delineation of target or organ at risk volumes. MRI use for treatment response assessment, MRI-only RT and other RT treatment types such as brachytherapy and gamma radiosurgery are not considered within the scope of this document. The aim was to produce guidance that will be useful for institutions who are setting up and using a dedicated MR scanner for RT (referred to as an MR-sim) and those who will have limited time on an MR scanner potentially managed outside of the RT department, often by radiology. Although not specifically covered in this document, there is an increase in the use of hybrid MRI-linac systems worldwide and brief comments are included to highlight any crossover with the early implementation of this technology. In this document, advice is given on introducing a RT workload onto a non-RT-dedicated MR scanner, as well as planning for installation of an MR scanner dedicated for RT. Next, practical guidance is given on the following, in the context of RT planning: training and education for all staff working in and around an MR scanner; RT patient set-up on an MR scanner; MRI sequence optimisation for RT purposes; commissioning and quality assurance (QA) to be performed on an MR scanner; and MRI to CT registration, including commissioning and QA.

IPEM Topical Report: A 2018 IPEM survey of MRI use for external beam radiotherapy treatment planning in the UK.

The benefits of integrating MRI into the radiotherapy pathway are well published, however there is little consensus in guidance on how to commission or implement its use. With a view to developing consensus guidelines for the use of MRI in external beam radiotherapy (EBRT) treatment planning in the UK, a survey was undertaken by an Institute of Physics and Engineering in Medicine (IPEM) working-party to assess the current landscape of MRI use in EBRT in the UK. A multi-disciplinary working-party developed a survey to understand current practice using MRI for EBRT treatment planning; investigate how MRI is currently used and managed; and identify knowledge gaps. The survey was distributed electronically to radiotherapy service managers and physics leads in 71 UK radiotherapy (RT) departments (all NHS and private groups). The survey response rate was 87% overall, with 89% of NHS and 75% of private centres responding. All responding centres include EBRT in some RT pathways: 94% using Picture Archiving and Communication System (PACS) images potentially acquired without any input from RT departments, and 69% had some form of MRI access for planning EBRT. Most centres reporting direct access use a radiology scanner within the same hospital in dedicated (26%) or non-dedicated (52%) RT scanning sessions. Only two centres reported having dedicated RT MRI scanners in the UK, lower than reported in other countries. Six percent of radiotherapy patients in England (data not publically available outside of England) have MRI as part of their treatment, which again is lower than reported elsewhere. Although a substantial number of centres acquire MRI scans for treatment planning purposes, most centres acquire less than five patient scans per month for each treatment site. Commissioning and quality assurance of both image registration and MRI scanners was found to be variable across the UK. In addition, staffing models and training given to different staff groups varied considerably across the UK, reflecting the current lack of national guidelines. The primary barriers reported to MRI implementation in EBRT planning included costs (e.g. lack of a national tariff for planning MRI), lack of MRI access and/or capacity within hospitals. Despite these challenges, significant interest remains in increasing MRI-assisted EBRT planning over the next five years.

MRI commissioning of 1.5T MR-linac systems - a multi-institutional study.

BACKGROUND: Magnetic Resonance linear accelerator (MR-linac) systems represent a new type of technology that allows for online MR-guidance for high precision radiotherapy (RT). Currently, the first MR-linac installations are being introduced clinically. Since the imaging performance of these integrated MR-linac systems is critical for their application, a thorough commissioning of the MRI performance is essential. However, guidelines on the commissioning of MR-guided RT systems are not yet defined and data on the performance of MR-linacs are not yet available. MATERIALS & METHODS: Here we describe a comprehensive commissioning protocol, which contains standard MRI performance measurements as well as dedicated hybrid tests that specifically assess the interactions between the Linac and the MRI system. The commissioning results of four MR-linac systems are presented in a multi-center study. RESULTS: Although the four systems showed similar performance in all the standard MRI performance tests, some differences were observed relating to the hybrid character of the systems. Field homogeneity measurements identified differences in the gantry shim configuration, which was later confirmed by the vendor. CONCLUSION: Our results highlight the importance of dedicated hybrid commissioning tests and the ability to compare the machines between institutes at this very early stage of clinical introduction. Until formal guidelines and tolerances are defined the tests described in this study may be used as a practical guideline. Moreover, the multi-center results provide initial bench mark data for future MR-linac installations.

Magnetic resonance imaging in precision radiation therapy for lung cancer.

Radiotherapy remains the cornerstone of curative treatment for inoperable locally advanced lung cancer, given concomitantly with platinum-based chemotherapy. With poor overall survival, research efforts continue to explore whether integration of advanced radiation techniques will assist safe treatment intensification with the potential for improving outcomes. One advance is the integration of magnetic resonance imaging (MRI) in the treatment pathway, providing anatomical and functional information with excellent soft tissue contrast without exposure of the patient to radiation. MRI may complement or improve the diagnostic staging accuracy of F-18 fluorodeoxyglucose position emission tomography and computerized tomography imaging, particularly in assessing local tumour invasion and is also effective for identification of nodal and distant metastatic disease. Incorporating anatomical MRI sequences into lung radiotherapy treatment planning is a novel application and may improve target volume and organs at risk delineation reproducibility. Furthermore, functional MRI may facilitate dose painting for heterogeneous target volumes and prediction of normal tissue toxicity to guide adaptive strategies. MRI sequences are rapidly developing and although the issue of intra-thoracic motion has historically hindered the quality of MRI due to the effect of motion, progress is being made in this field. Four-dimensional MRI has the potential to complement or supersede 4D CT and 4D F-18-FDG PET, by providing superior spatial resolution. A number of MR-guided radiotherapy delivery units are now available, combining a radiotherapy delivery machine (linear accelerator or cobalt-60 unit) with MRI at varying magnetic field strengths. This novel hybrid technology is evolving with many technical challenges to overcome. It is anticipated that the clinical benefits of MR-guided radiotherapy will be derived from the ability to adapt treatment on the fly for each fraction and in real-time, using 'beam-on' imaging. The lung tumour site group of the Atlantic MR-Linac consortium is working to generate a challenging MR-guided adaptive workflow for multi-institution treatment intensification trials in this patient group.

Effect of wavelength and beam width on penetration in light-tissue interaction using computational methods.

Penetration depth of ultraviolet, visible light and infrared radiation in biological tissue has not previously been adequately measured. Risk assessment of typical intense pulsed light and laser intensities, spectral characteristics and the subsequent chemical, physiological and psychological effects of such outputs on vital organs as consequence of inappropriate output use are examined. This technical note focuses on wavelength, illumination geometry and skin tone and their effect on the energy density (fluence) distribution within tissue. Monte Carlo modelling is one of the most widely used stochastic methods for the modelling of light transport in turbid biological media such as human skin. Using custom Monte Carlo simulation software of a multi-layered skin model, fluence distributions are produced for various non-ionising radiation combinations. Fluence distributions were analysed using Matlab mathematical software. Penetration depth increases with increasing wavelength with a maximum penetration depth of 5378 µm calculated. The calculations show that a 10-mm beam width produces a fluence level at target depths of 1-3 mm equal to 73-88% (depending on depth) of the fluence level at the same depths produced by an infinitely wide beam of equal incident fluence. Meaning little additional penetration is achieved with larger spot sizes. Fluence distribution within tissue and thus the treatment efficacy depends upon the illumination geometry and wavelength. To optimise therapeutic techniques, light-tissue interactions must be thoroughly understood and can be greatly supported by the use of mathematical modelling techniques.