Geometric distortions in clinical MRI sequences for radiotherapy: insights gained from a multicenter investigation.

BACKGROUND: As magnetic resonance imaging (MRI) becomes increasingly integrated into radiotherapy (RT) for enhanced treatment planning and adaptation, the inherent geometric distortion in acquired MR images pose a potential challenge to treatment accuracy. This study aimed to evaluate the geometric distortion levels in the clinical MRI protocols used across Danish RT centers and discuss influence of specific sequence parameters. Based on the variety in geometric performance across centers, we assess if harmonization of MRI sequences is a relevant measure. MATERIALS AND METHODS: Nine centers participated with 12 MRI scanners and MRI-Linacs (MRL). Using a travelling phantom approach, a reference MRI sequence was used to assess variation in baseline distortion level between scanners. The phantom was also scanned with local clinical MRI sequences for brain, head/neck (H/N), abdomen, and pelvis. The influence of echo time, receiver bandwidth, image weighting, and 2D/3D acquisition was investigated. RESULTS: We found a large variation in geometric accuracy across 93 clinical sequences examined, exceeding the baseline variation found between MRI scanners (σ = 0.22 mm), except for abdominal sequences where the variation was lower. Brain and abdominal sequences showed lowest distortion levels ([0.22, 2.26] mm), and a large variation in performance was found for H/N and pelvic sequences ([0.19, 4.07] mm). Post hoc analyses revealed that distortion levels decreased with increasing bandwidth and a less clear increase in distortion levels with increasing echo time. 3D MRI sequences had lower distortion levels than 2D (median of 1.10 and 2.10 mm, respectively), and in DWI sequences, the echo-planar imaging read-out resulted in highest distortion levels. CONCLUSION: There is a large variation in the geometric distortion levels of clinical MRI sequences across Danish RT centers, and between anatomical sites. The large variation observed makes harmonization of MRI sequences across institutions and adoption of practices from well-performing anatomical sites, a relevant measure within RT.

A national study on the inter-observer variability in the delineation of organs at risk in the brain.

BACKGROUND: The Danish Neuro Oncology Group (DNOG) has established national consensus guidelines for the delineation of organs at risk (OAR) structures based on published literature. This study was conducted to finalise these guidelines and evaluate the inter-observer variability of the delineated OAR structures by expert observers. MATERIAL AND METHODS: The DNOG delineation guidelines were formed by participants from all Danish centres that treat brain tumours with radiotherapy. In a two-day workshop, guidelines were discussed and finalised based on a pilot study. Following this, the ten participants contoured the following OARs on T1-weighted gadolinium enhanced MRI from 13 patients with brain tumours: optic tracts, optic nerves, chiasm, spinal cord, brainstem, pituitary gland and hippocampus. The metrics used for comparison were the Dice similarity coefficient (Dice), mean surface distance (MSD) and others. RESULTS: A total of 968 contours were delineated across the 13 patients. On average eight (range six to nine) individual contour sets were made per patient. Good agreement was found across all structures with a median MSD below 1 mm for most structures, with the chiasm performing the best with a median MSD of 0.45 mm. The Dice was as expected highly volume dependent, the brainstem (the largest structure) had the highest Dice value with a median of 0.89 whereas smaller volumes such as the chiasm had a Dice of 0.71. CONCLUSION: Except for the caudal definition of the spinal cord, the variances observed in the contours of OARs in the brain were generally low and consistent. Surface mapping revealed sub-regions of higher variance for some organs. The data set is being prepared as a validation data set for auto-segmentation algorithms for use within the Danish Comprehensive Cancer Centre - Radiotherapy and potential collaborators.

Diffusion-weighted magnetic resonance imaging during radiotherapy of locally advanced cervical cancer--treatment response assessment using different segmentation methods.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) and the derived apparent diffusion coefficient (ADC) value has potential for monitoring tumor response to radiotherapy (RT). Method used for segmentation of volumes with reduced diffusion will influence both volume size and observed distribution of ADC values. This study evaluates: 1) different segmentation methods; and 2) how they affect assessment of tumor ADC value during RT. MATERIAL AND METHODS: Eleven patients with locally advanced cervical cancer underwent MRI three times during their RT: prior to start of RT (PRERT), two weeks into external beam RT (WK2RT) and one week prior to brachytherapy (PREBT). Volumes on DW-MRI were segmented using three semi-automatic segmentation methods: "cluster analysis", "relative signal intensity (SD4)" and "region growing". Segmented volumes were compared to the gross tumor volume (GTV) identified on T2-weighted MR images using the Jaccard similarity index (JSI). ADC values from segmented volumes were compared and changes of ADC values during therapy were evaluated. RESULTS: Significant difference between the four volumes (GTV, DWIcluster, DWISD4 and DWIregion) was found (p < 0.01), and the volumes changed significantly during treatment (p < 0.01). There was a significant difference in JSI among segmentation methods at time of PRERT (p < 0.016) with region growing having the lowest JSIGTV (mean± sd: 0.35 ± 0.1), followed by the SD4 method (mean± sd: 0.50 ± 0.1) and clustering (mean± sd: 0.52 ± 0.3). There was no significant difference in mean ADC value compared at same treatment time. Mean tumor ADC value increased significantly (p < 0.01) for all methods across treatment time. CONCLUSION: Among the three semi-automatic segmentations of hyper-intense intensities on DW-MR images implemented, cluster analysis and relative signal thresholding had the greatest similarity to the clinical tumor volume. Evaluation of mean ADC value did not depend on segmentation method.

Tracer kinetic model selection for dynamic contrast-enhanced magnetic resonance imaging of locally advanced cervical cancer.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers a unique capability to probe tumour microvasculature. Different analysis of the acquired data will possibly lead to different conclusions. Therefore, the objective of this study was to investigate under which conditions the Tofts (TM), extended Tofts (ETM), compartmental tissue uptake model (C-TU) and 2-compartment exchange model (2CXM) were the optimal tracer kinetic models (TKMs) for the analysis of DCE-MRI in patients with cervical cancer. MATERIAL AND METHODS: Ten patients with locally advanced cervical cancer (FIGO: IIA/IIB/IIIB/IVA - 1/5/3/1) underwent DCE-MRI prior to radiotherapy. From the two-parameter TM it was possible to extract the forward volume transfer constant (K(trans)) and the extracellular-extravascular volume fraction (ve). From the three-parameter ETM, additionally the plasma volume fraction (vp) could be extracted. From the three-parameter C-TU it was possible to extract information about the blood flow (Fp), permeability-surface area product (PS) and vp. Finally, the four-parameter 2CXM extended the C-TU to include ve. For each voxel, corrected Akaike information criterion (AICc) values were calculated, taking into account both the goodness-of-fit and the number of model parameters. The optimal model was defined as the model with the lowest AICc. RESULTS: All four TKMs were the optimal model in different contiguous regions of the cervical tumours. For the 24 999 analysed voxels, the TM was optimal in 17.0%, the ETM was optimal in 2.2%, the C-TU in 23.4% and the 2CXM was optimal in 57.3%. Throughout the tumour, a high correlation was found between K(trans)(TM) and Fp(2CXM), ρ = 0.91. CONCLUSION: The 2CXM was most often optimal in describing the contrast agent enhancement of pre-treatment cervical cancers, although this model broke down in a subset of the tumour voxels where overfitting resulted in non-physiological parameter estimates. Due to the possible overfitting of the 2CXM, the C-TU was found more robust and when 2CXM was excluded from comparison the C-TU was the preferred model.

Apparent Diffusion Coefficient (ADC) as a quantitative parameter in diffusion weighted MR imaging in gynecologic cancer: Dependence on b-values used.

BACKGROUND: Diffusion weighted imaging (DWI) has gained interest as an imaging modality for assessment of tumor extension and response to cancer treatment. The purpose of this study is to assess the impact of the choice of b-values on the calculation of the Apparent Diffusion Coefficient (ADC) for locally advanced gynecological cancer and to estimate a stable interval of diffusion gradients that allows for best comparison of the ADC between patients and institutions. MATERIAL AND METHODS: Six patients underwent a high resolution single shot EPI based DWI scan with 16 different diffusion gradients on a 3 Tesla Philips Achieva MR-scanner. Data analysis was performed by applying a monoexponential and a biexponential model to the acquired data. The biexponential function models the effect of both perfusion and diffusion. RESULTS AND CONCLUSION: ADC changes of up to 40% were seen with the use of different b-values. Using a lower b-value ≥ 150 s/mm(2) and an upper b-value ≥ 700 s/mm(2) limited the variation to less that 10% from the reference ADC value. By eliminating the contribution of perfusion the uncertainty of quantitative ADC values were significantly reduced.

Cognitive impairment following radiation to hippocampus and other brain structures in adults with primary brain tumours.

BACKGROUND: Radiation therapy (RT) to the brain may result in cognitive impairment. The primary objective of the present study was to examine the relationship between RT dose to the hippocampus and learning and memory functions. Secondary objective was to examine relationships between doses to other brain structures and specific cognitive functions. METHODS: A cross-sectional analysis was undertaken in 78 primary brain tumour patients after RT. Cognitive function was assessed by neuropsychological tests. Test scores were standardized using normative data adjusted for age and level of education. Test-specific cognitive impairment was determined as a z-score ≤-1.5. Radiation dose to brain structures and test-specific cognitive impairment outcomes were fitted to a logistic regression model. RESULTS: High RT dose to the left hippocampus was associated with impaired verbal learning and memory (p = 0.04). RT dose to the left hippocampus, left temporal lobe, left frontal lobe and total frontal lobe were associated with verbal fluency impairment (p < 0.05) and doses to the thalamus and the left frontal lobe with impaired executive functioning (p ≤ 0.03). Finally, RT dose to the brain and thalamus were associated with impaired processing speed (p ≤ 0.05). CONCLUSION: The present study indicates that the hippocampus may be vulnerable to radiation and that high radiation doses to the left hippocampus may lead to significant verbal learning and memory impairment. High RT doses to the left hippocampus and other left side structures may result in impairments in verbal fluency, executive function, and processing speed. Validation of these findings are being undertaken in a prospective study.

An adaptive radiotherapy planning strategy for bladder cancer using deformation vector fields.

PURPOSE: Adaptive radiotherapy (ART) has considerable potential in treatment of bladder cancer due to large inter-fractional changes in shape and size of the target. The aim of this study was to compare our clinically applied method for plan library creation that involves manual bladder delineations (Clin-ART) with a method using the deformation vector fields (DVFs) resulting from intensity-based deformable image registrations (DVF-based ART). MATERIALS AND METHODS: The study included thirteen patients with urinary bladder cancer who had daily cone beam CTs (CBCTs) acquired for set-up. In both ART strategies investigated, three plan selection volumes were generated using the CBCTs from the first four fractions; in Clin-ART boolean combinations of delineated bladders were used, while the DVF-based strategy applied combinations of the mean and standard deviation of patient-specific DVFs. The volume ratios (VRs) of the course-averaged PTV for the two ART strategies relative the non-adaptive PTV were calculated. RESULTS: Both Clin-ART and DVF-based ART considerably reduced the course-averaged PTV, compared to non-adaptive RT. The VR for DVF-based ART was lower than for Clin-ART (0.65 vs. 0.73; p<0.01). CONCLUSIONS: DVF-based ART for bladder irradiation has a considerable normal tissue sparing potential surpassing our already highly conformal clinically applied ART strategy.