The future of MRI in radiation therapy: Challenges and opportunities for the MR community.

Radiation therapy is a major component of cancer treatment pathways worldwide. The main aim of this treatment is to achieve tumor control through the delivery of ionizing radiation while preserving healthy tissues for minimal radiation toxicity. Because radiation therapy relies on accurate localization of the target and surrounding tissues, imaging plays a crucial role throughout the treatment chain. In the treatment planning phase, radiological images are essential for defining target volumes and organs-at-risk, as well as providing elemental composition (e.g., electron density) information for radiation dose calculations. At treatment, onboard imaging informs patient setup and could be used to guide radiation dose placement for sites affected by motion. Imaging is also an important tool for treatment response assessment and treatment plan adaptation. MRI, with its excellent soft tissue contrast and capacity to probe functional tissue properties, holds great untapped potential for transforming treatment paradigms in radiation therapy. The MR in Radiation Therapy ISMRM Study Group was established to provide a forum within the MR community to discuss the unmet needs and fuel opportunities for further advancement of MRI for radiation therapy applications. During the summer of 2021, the study group organized its first virtual workshop, attended by a diverse international group of clinicians, scientists, and clinical physicists, to explore our predictions for the future of MRI in radiation therapy for the next 25 years. This article reviews the main findings from the event and considers the opportunities and challenges of reaching our vision for the future in this expanding field.

On the dependence of quantitative diffusion-weighted imaging on scanner system characteristics and acquisition parameters: A large multicenter and multiparametric phantom study with unsupervised clustering analysis.

PURPOSE: The purpose of this multicenter phantom study was to exploit an innovative approach, based on an extensive acquisition protocol and unsupervised clustering analysis, in order to assess any potential bias in apparent diffusion coefficient (ADC) estimation due to different scanner characteristics. Moreover, we aimed at assessing, for the first time, any effect of acquisition plan/phase encoding direction on ADC estimation. METHODS: Water phantom acquisitions were carried out on 39 scanners. DWI acquisitions (b-value = 0-200-400-600-800-1000 s/mm2) with different acquisition plans (axial, coronal, sagittal) and phase encoding directions (anterior/posterior and right/left, for the axial acquisition plan), for 3 orthogonal diffusion weighting gradient directions, were performed. For each acquisition setup, ADC values were measured in-center and off-center (6 different positions), resulting in an entire dataset of 84 × 39 = 3276 ADC values. Spatial uniformity of ADC maps was assessed by means of the percentage difference between off-center and in-center ADC values (Δ). RESULTS: No significant dependence of in-center ADC values on acquisition plan/phase encoding direction was found. Ward unsupervised clustering analysis showed 3 distinct clusters of scanners and an association between Δ-values and manufacturer/model, whereas no association between Δ-values and maximum gradient strength, slew rate or static magnetic field strength was revealed. Several acquisition setups showed significant differences among groups, indicating the introduction of different biases in ADC estimation. CONCLUSIONS: Unsupervised clustering analysis of DWI data, obtained from several scanners using an extensive acquisition protocol, allows to reveal an association between measured ADC values and manufacturer/model of scanner, as well as to identify suboptimal DWI acquisition setups for accurate ADC estimation.

Is there a correlation between 3T multiparametric MRI and molecular subtypes of breast cancer?

OBJECTIVES: To test whether 3 T multiparametric magnetic resonance imaging (mMRI) provides information related to molecular subtypes of breast cancer. METHODS: Women with mammographic or US findings of breast lesions (BI-RADS 4-5) underwent 3 T mMRI (DCE, DWI and MR spectroscopy). The histological type of breast cancer was assessed. Estrogen-receptor (ER), progesterone-receptor (PgR), Ki-67 status and HER-2 expression, assessed by immunohistochemistry (IHC), defined four molecular subtypes: Luminal-A, Luminal-B, HER2-enriched and triple-negative. Non-parametric tests (Kruskal-Wallis, k-sample equality of medians, and Mann-Whitney), logistic regression or ANOVA, and a multivariate analysis were performed to investigate correlations between the four molecular subtypes and mMRI (lesion volume, margins or distribution, enhancement pattern, ADC, type of kinetic curve, and total choline (tCho) signal-to-noise-ratio (SNR)). A ROC analysis was finally performed to test the diagnostic power of a multivariate logistic regression model. RESULTS: 433 patients (453 lesions) were considered. Volume was smaller in Luminal-B and larger in triple-negative tumours compared to the other subtypes combined. Margins were significantly correlated to Luminal-A and Luminal-B. The type of curve was significantly correlated to Luminal-A. ADC values were higher in Luminal-A. tCho SNR was higher in triple-negative tumours. The ROC analysis showed that the area under the curve (AUC) significantly improved when multiple MRI features were used compared to individual parameters. CONCLUSIONS: A significant correlation was found between some MRI features and molecular subtypes of breast tumours. A multiparametric approach improved the diagnostic power of MRI. However, further research is needed in order to predict the molecular subtype on the sole basis of mMRI.

Dependence of apparent diffusion coefficient measurement on diffusion gradient direction and spatial position - A quality assurance intercomparison study of forty-four scanners for quantitative diffusion-weighted imaging.

PURPOSE: To propose an MRI quality assurance procedure that can be used for routine controls and multi-centre comparison of different MR-scanners for quantitative diffusion-weighted imaging (DWI). MATERIALS AND METHODS: 44 MR-scanners with different field strengths (1 T, 1.5 T and 3 T) were included in the study. DWI acquisitions (b-value range 0-1000 s/mm2), with three different orthogonal diffusion gradient directions, were performed for each MR-scanner. All DWI acquisitions were performed by using a standard spherical plastic doped water phantom. Phantom solution ADC value and its dependence with temperature was measured using a DOSY sequence on a 600 MHz NMR spectrometer. Apparent diffusion coefficient (ADC) along each diffusion gradient direction and mean ADC were estimated, both at magnet isocentre and in six different position 50 mm away from isocentre, along positive and negative AP, RL and HF directions. RESULTS: A good agreement was found between the nominal and measured mean ADC at isocentre: more than 90% of mean ADC measurements were within 5% from the nominal value, and the highest deviation was 11.3%. Away from isocentre, the effect of the diffusion gradient direction on ADC estimation was larger than 5% in 47% of included scanners and a spatial non uniformity larger than 5% was reported in 13% of centres. CONCLUSION: ADC accuracy and spatial uniformity can vary appreciably depending on MR scanner model, sequence implementation (i.e. gradient diffusion direction) and hardware characteristics. The DWI quality assurance protocol proposed in this study can be employed in order to assess the accuracy and spatial uniformity of estimated ADC values, in single- as well as multi-centre studies.

1H-MR spectroscopy of suspicious breast mass lesions at 3T: a clinical experience.

OBJECTIVES: To test 3T proton magnetic resonance spectroscopy (1H-MRS) for breast mass lesions. METHODS: Patients with BI-RADS 4-5 lesions at mammography/ultrasound were prospectively enrolled. After contrast-enhanced breast MRI, single-voxel MRS (point-resolved volume selection, PRESS); pencil-beam shimming; volume of interest 1 cm3; TR/TE = 3000/135 ms) was performed. Spectra were considered reliable if the full width at half maximum (FWHM) of the water peak was ≤45 Hz. A signal-to-noise ratio of the total choline (tCho) peak at 3.21 ppm ≥2 was used as cutoff for malignancy. All lesions underwent needle sampling. Final pathology was available for all malignant lesions; for benign lesions the reference standard was final pathology or at least 1-year negative follow-up. RESULTS: Reliable spectra were obtained in 115/127 lesions (91%), with a mean FWHM of 32.4 Hz (range 8-45 Hz). A tCho peak SNR ≥2 was detected in 66 malignant lesions (62 invasive cancers; 4 ductal carcinoma in situ) and in 3 benign lesions. Excluding lesions located ≤1 cm from the skin (n = 3) or pectoral muscle (n = 11), sensitivity was 65/73 [89%, 95% confidence interval (CI): 80-95%], and specificity 25/28 (89%) (95% CI: 72-98%). Considering only invasive cancers, sensitivity reached 61/68 (90%, 95% CI: 81-96%). MRS additional time was 8 min. CONCLUSIONS: When lesions close to the skin or pectoral muscle are excluded, 3T 1H-MRS of mass lesions ≥1 cm showed a high diagnostic performance, however, insufficient to avoid needle biopsy.

High-field MR spectroscopy in the multiparametric MRI evaluation of breast lesions.

INTRODUCTION: The aim of this work was to assess the role of 3T-MR spectroscopy (MRS) in the multi-parametric MRI evaluation of breast lesions, using a pattern-recognition based classification method. METHODS: 291 patients (301 lesions, median 2.3cm3) were enrolled in the study (age 18-85y, mean 54.2y). T1-TSE (TR/TE=400/10ms) and T2-STIR imaging (TR/TE=5000/60ms), dynamic-contrast-enhanced MRI (DCE-MRI), apparent diffusion coefficient (ADC) (b=0-800s/mm2), and single-voxel MRS (10×10×10mm3, PRESS, TR/TE=3000ms/135ms) were performed by means of a 3T scanner. MRS results were accepted if the FWHM of the water peak was ⩽45Hz. Total choline (tCho) was considered detected if the signal-to-noise ratio (SNR) of the 3.2ppmpeak was ⩾2. A classifier-based analysis (support-vector-machines, SVM) was performed with 4-dimensional vectors including type of margin, DCE-MRI kinetic curve type, ADC mean value, and tCho SNR. A comparison with 3-dimensional vectors (without tCho SNR) was used to assess MRS impact on sensitivity, specificity, and positive-negative predictive values (PPV-NPV) for malignancy. RESULTS: 228 lesions (180 malignant/48 benign) showed acceptable spectral quality. Comparison of classification results with histopathological examination of surgical specimens showed sensitivity=93.7%, specificity=84.9%, PPV=95.2%, NPV=81.5% without the inclusion of MRS in the SVM analysis. When MRS was included, the figures increased to 95.1%, 90.7%, 97.2%, and 85.0%, respectively. CONCLUSIONS: Inclusion of 3T-MRS in the multi-parametric MRI evaluation of breast lesions improved the performance of the SVM-based classifier, showing a possible role of high-field MR spectroscopy in the differential diagnosis between benign and malignant breast lesions. Further research is however needed to confirm this initial evidence.

Quality assurance multicenter comparison of different MR scanners for quantitative diffusion-weighted imaging.

PURPOSE: To propose a magnetic resonance imaging (MRI) quality assurance procedure that can be used for multicenter comparison of different MR scanners for quantitative diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Twenty-six centers (35 MR scanners with field strengths: 1T, 1.5T, and 3T) were enrolled in the study. Two different DWI acquisition series (b-value ranges 0-1000 and 0-3000 s/mm(2) , respectively) were performed for each MR scanner. All DWI acquisitions were performed by using a cylindrical doped water phantom. Mean apparent diffusion coefficient (ADC) values as well as ADC values along each of the three main orthogonal directions of the diffusion gradients (x, y, and z) were calculated. Short-term repeatability of ADC measurement was evaluated for 26 MR scanners. RESULTS: A good agreement was found between the nominal and measured mean ADC over all the centers. More than 80% of mean ADC measurements were within 5% from the nominal value, and the highest deviation and overall standard deviation were 9.3% and 3.5%, respectively. Short-term repeatability of ADC measurement was found <2.5% for all MR scanners. CONCLUSION: A specific and widely accepted protocol for quality controls in DWI is still lacking. The DWI quality assurance protocol proposed in this study can be applied in order to assess the reliability of DWI-derived indices before tackling single- as well as multicenter studies.

Accelerated partial breast irradiation using only intraoperative electron radiation therapy in early stage breast cancer.

BACKGROUND: We report the results of a single-institution, phase II trial of accelerated partial breast irradiation (APBI) using a single dose of intraoperative electron radiation therapy (IOERT) in patients with low-risk early stage breast cancer. METHODS AND MATERIALS: A cohort of 226 patients with low-risk, early stage breast cancer were treated with local excision and axillary management (sentinel node biopsy with or without axillary node dissection). After the surgeon temporarily reapproximated the excision cavity, a dose of 21 Gy using IOERT was delivered to the tumor bed, with a margin of 2 cm laterally. RESULTS: With a mean follow-up of 46 months (range, 28-63 months), only 1 case of local recurrence was reported. The observed toxicity was considered acceptable. CONCLUSIONS: APBI using a single dose of IOERT can be delivered safely in women with early, low-risk breast cancer in carefully selected patients. A longer follow-up is needed to ascertain its efficacy compared to that of the current standard treatment of whole-breast irradiation.