Dynamic Contrast-enhanced Magnetic Resonance Imaging Evaluation of Whole Tumour Perfusion Heterogeneity Predicts Distant Disease-free Survival in Locally Advanced Rectal Cancer.

AIMS: To evaluate diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging for the prediction of disease-free survival (DFS) in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with stage II or III rectal adenocarcinoma undergoing neoadjuvant chemoradiotherapy (CRT) and surgery were eligible. Patients underwent multi-parametric magnetic resonance imaging (diffusion-weighted imaging and dynamic contrast-enhanced) before CRT, during CRT (week 3) and after CRT (1 week prior to surgery). Whole tumour apparent diffusion coefficient (ADC) and Ktrans histogram quantiles (10th, 25th, 50th, 75th, 90th) were extracted for analysis. The associations between ADC and Ktrans at three timepoints with time to relapse were analysed as a continuous variable using a Cox proportional hazard model. RESULTS: Thirty-three patients were included in this analysis. The median follow-up was 4.4 years. No patient had locoregional relapse. Nine patients developed distant metastases. The hazard ratios for after CRT Ktrans 10th (P = 0.035), 25th (P = 0.048), 50th (P = 0.046) and 75th (P = 0.045) quantiles were statistically significant for DFS. The best Ktrans cut-off point after CRT for predicting relapse was 28 × 10-3 mL/g/min (10th quantile), with a higher Ktrans value predicting distant relapse. The 4-year DFS probability was 0.93 for patients with after CRT Ktrans value ≤28 × 10-3 mL/g/min versus 0.45 for patients with after CRT Ktrans value >28 × 10-3 mL/g/min. ADC was not able to predict DFS. CONCLUSIONS: Patients with higher Ktrans values after CRT (before surgery) in a histogram analysis of whole tumour heterogeneity had a significantly lower 4-year distant DFS and could be considered for more intense systemic therapy.

Quantitative MRI: Defining repeatability, reproducibility and accuracy for prostate cancer imaging biomarker development.

INTRODUCTION: Quantitative MRI (qMRI) parameters have been increasingly used to develop predictive models to accurately monitor treatment response in prostate cancer after radiotherapy. To reliably detect changes in signal due to treatment response, predictive models require qMRI parameters with high repeatability and reproducibility. The purpose of this study was to measure qMRI parameter uncertainties in both commercial and in-house developed phantoms to guide the development of robust predictive models for monitoring treatment response. MATERIALS AND METHODS: ADC, T1, and R2* values were acquired across three 3 T scanners with a prostate-specific qMRI protocol using the NIST/ISMRM system phantom, RSNA/NIST diffusion phantom, and an in-house phantom. A B1 field map was acquired to correct for flip angle inhomogeneity in T1 maps. All sequences were repeated in each scan to assess within-session repeatability. Weekly scans were acquired on one scanner for three months with the in-house phantom. Between-session repeatability was measured with test-retest scans 6-months apart on all scanners with all phantoms. Accuracy, defined as percentage deviation from reference value for ADC and T1, was evaluated using the system and diffusion phantoms. Repeatability and reproducibility coefficients of variation (%CV) were calculated for all qMRI parameters on all phantoms. RESULTS: Overall, repeatability CV of ADC was <2.40%, reproducibility CV was <3.98%, and accuracy ranged between -8.0% to 2.7% across all scanners. Applying B1 correction on T1 measurements significantly improved the repeatability and reproducibility (p<0.05) but increased error in accuracy (p<0.001). Repeatability and reproducibility of R2* was <4.5% and <7.3% respectively in the system phantom across all scanners. CONCLUSION: Repeatability, reproducibility, and accuracy in qMRI parameters from a prostate-specific protocol was estimated using both commercial and in-house phantoms. Results from this work will be used to identify robust qMRI parameters for use in the development of predictive models to longitudinally monitor treatment response for prostate cancer in current and future clinical trials.

Pelvic organ motion and dosimetric implications during horizontal patient rotation for prostate radiation therapy.

PURPOSE: Gantry-free radiation therapy systems utilizing patient rotation would be simpler and more cost effective than the conventional gantry-based systems. Such a system could enable the expansion of radiation therapy to meet global demand and reduce capital costs. Recent advances in adaptive radiation therapy could potentially be applied to correct for gravitational deformation during horizontal patient rotation. This study aims to quantify the pelvic organ motion and the dosimetric implications of horizontal rotation for prostate intensity-modulated radiation therapy (IMRT) treatments. METHODS: Eight human participants who previously received prostate radiation therapy were imaged in a clinical magnetic resonance imaging (MRI) scanner using a bespoke patient rotation system (PRS). The patients were imaged every 45 degrees during a full roll rotation (0-360 degrees). Whole pelvic bone, prostate, rectum, and bladder motion were compared to the supine position using dice similarity coefficient (DSC) and mean absolute surface distance (MASD). Prostate centroid motion was compared in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) direction prior to and following pelvic bone-guided rigid registration. Seven-field prostate IMRT treatment plans were generated for each patient rotation angles under three adaption scenarios: No plan adaption, rigid planning target volume (PTV)-guided alignment to the prostate, and plan re-optimization. Prostate, rectum, and bladder doses were compared for each adaption scenario. RESULTS: Pelvic bone motion within the PRS of up to 53 mm relative to the supine position was observed for some participants. Internal organ motion was greatest at the 180-degree PRS couch angle (prone), with prostate centroid motion range < 2 mm LR, 0 mm to 14 mm SI, and -11 mm to 4 mm AP. Rotation with no adaption of the treatment plan resulted in an underdose to the PTV -- in some instances up to 75% (D95%: 78 ± 0.3 Gy at supine to 20 ± 15.0 Gy at the 225-degree PRS couch angle). Bladder dose was reduced during the rotation by up to 98% (V60 Gy: 15.0 ± 9.4% supine to 0.3 ± 0.5% at the 225-degree PRS couch angle). In some instances, the rectum dose increased during rotation (V60Gy: 20.0 ± 4.5% supine to 25.0 ± 15.0% at the 135-degree PRS couch angle). Rigid PTV-guided alignment resulted in PTV coverage which, though statistically lower (P < 0.05 for all D95% values), was within 1 Gy of the supine plans. Plan re-optimization resulted in a statistically equivalent PTV coverage compared to the supine plans (P > 0.05 for all D95% metrics and all within ±0.4 Gy). For both rigid PTV-guided alignment and plan re-optimization, rectum dose volume metrics were reduced compared to the supine position between the 90- and 225-degree PRS couch angles (P < 0.05). Bladder dose volume metrics were not impacted by rotation. CONCLUSION: Pelvic bone and internal organ motion are present during patient rotation. Rigid PTV-guided alignment to the prostate will be a requirement if prostate IMRT is to be safely delivered using patient rotation. Plan re-optimization for each PRS couch angle to account for anatomical deformations further improves the PTV coverage.

Towards real-time 4D radiation dosimetry on an MRI-Linac.

4D radiation dosimetry using a highly radiation-sensitive polymer gel dosimeter with real-time quantitative magnetic resonance imaging (MRI) readout is presented as a technique to acquire the accumulated radiation dose distribution during image-guided radiotherapy on an MRI-Linac. Optimized T 2-weighted Turbo-Spin-Echo (TSE) scans are converted into quantitative ΔR 2 maps and subsequently to radiation dose maps. The concept of temporal uncertainty is introduced as a metric of effective temporal resolution. A mathematical framework is presented to optimize the echo time of the TSE sequence in terms of dose resolution, and the trade-off between temporal resolution and dose resolution is discussed. The current temporal uncertainty achieved with the MAGAT gel dosimeter on a 1 T MRI-Linac is 3.8 s which is an order of magnitude better than what has been achieved until now. The potential of real-time 4D radiation dosimetry in a theragnostic MRI-Linac is demonstrated for two scenarios: an irradiation with three coplanar beams on a head phantom and a dynamic arc treatment on a cylindrical gel phantom using a rotating couch. The dose maps acquired on the MRI-Linac are compared with a treatment plan and with dose maps acquired on a clinical 3 T MRI scanner. 3D gamma map evaluations for the different modalities are provided. While the presented method demonstrates the potential of gel dosimetry for tracking the dose delivery during radiotherapy in 4D, a shortcoming of the MAGAT gel dosimeter is a retarded dose response. The effect of non-ideal radiofrequency pulses resulting from limitations in the specific absorption rate or B1-field inhomogeneity on the TSE acquired ΔR 2 values is analysed experimentally and by use of computational modelling with a Bloch simulator.

Anatomical deformation due to horizontal rotation: towards gantry-free radiation therapy.

Gantry-free radiation therapy systems may be simpler and more cost effective, particularly for MRI-guided photon or hadron therapy. This study aims to understand and quantify anatomical deformations caused by horizontal rotation with scan sequences sufficiently short to facilitate integration into an MRI-guided workflow. Rigid and non-rigid pelvic deformations due to horizontal rotation were quantified for a cohort of 8 healthy volunteers using a bespoke patient rotation system and a clinical MRI scanner. For each volunteer a reference scan was acquired at 0° followed by sequential faster scans in 45° increments through to 360°. All fast scans were registered to the 0° image via a three-step process: first, images were aligned using MR visible couch markers. Second, the scans were pre-processed then rigidly registered to the 0° image. Third, the rigidly registered scans were non-rigidly registered to the 0° image to assess soft tissue deformation. The residual differences after rigid and non-rigid registration were determined from the transformation matrix and the deformation vector field, respectively. The rigid registration yielded mean rotations of ⩽2.5° in all cases. The average 3D translational magnitudes range was 5.8 ± 2.9 mm-30.0 ± 11.0 mm. Translations were most significant in the left-right (LR) direction. Smaller translations were observed in the anterior-posterior (AP) and superior-inferior (SI) directions. The maximum deformation magnitudes range was: 10.0 ± 0.9 mm-28.0 ± 2.8 mm and average deformation magnitudes range: 2.3 ± 0.6 mm-7.5 ± 1.0 mm. Average non-rigid deformation magnitude was correlated with BMI (correlation coefficient 0.84, p  = 0.01). Rigid pelvic deformations were most significant in the LR direction but could be accounted for with on-line adjustments. Non-rigid deformations can be significant and will need to be accounted for in order to facilitate the delivery of gantry-free therapy with an automated patient rotation system.

MRI-Linear Accelerator Radiotherapy Systems.

The desire to utilise soft-tissue image guidance at the time of radiation treatment has led to the development of several hybrid magnetic resonance imaging (MRI) linear accelerators (linacs). These systems have the potential to realise the benefits of MRI on the treatment table with the ability of real-time motion management and adaption on a patient-specific basis. There are several MRI-linacs currently being implemented covering both low and high magnetic field strength and two beam-field orientations. Clinical trials have only recently begun with this technology, but their future use as standard radiotherapy practice seems assured. This review article summarises the challenges faced in developing such hybrid technology, the differences and advantages of each of the currently exploited solutions, and their current status.

Imaging performance of a dedicated radiation transparent RF coil on a 1.0 Tesla inline MRI-linac.

This work describes the first imaging studies on a 1.0 Tesla inline MRI-Linac using a dedicated transmit/receive RF body coil that has been designed to be completely radio transparent and provide optimum imaging performance over a large patient opening. A series of experiments was performed on the MRI-Linac to investigate the performance and imaging characteristics of a new dedicated volumetric RF coil: (1) numerical electromagnetic simulations were used to measure transmit efficiency in two patient positions; (2) image quality metrics of signal-to-noise ratio (SNR), ghosting and uniformity were assessed in a large diameter phantom with no radiation beam; (3) radiation induced effects were investigated in both the raw data (k-space) and image sequences acquired with simultaneous irradiation; (4) radiation dose was measured with and without image acquisition; (5) RF heating was studied using an MR-compatible fluoroptic thermometer and; (6) the in vivo image quality and versatility of the coil was demonstrated in normal healthy subjects for both supine and standing positions. Daily phantom measurements demonstrated excellent imaging performance with stable SNR over a period of 3 months (42.6 ± 0.9). Simultaneous irradiation produced no statistical change in image quality (p > 0.74) and no interference in raw data for a 20 × 20 cm radiation field. The coil was found to be efficient over large volumes and negligible RF heating was observed. Volunteer scans acquired in both supine and standing positions provided artefact free images with good anatomical visualisation. The first completely radio transparent RF coil for use on a 1.0 Tesla MRI-Linac has been described. There is no impact on either the imaging or dosimetry performance with a simultaneous radiation beam. The open design enables imaging and radiotherapy guidance in a variety of positons.

Towards real-time MRI-guided 3D localization of deforming targets for non-invasive cardiac radiosurgery.

Radiosurgery to the pulmonary vein antrum in the left atrium (LA) has recently been proposed for non-invasive treatment of atrial fibrillation (AF). Precise real-time target localization during treatment is necessary due to complex respiratory and cardiac motion and high radiation doses. To determine the 3D position of the LA for motion compensation during radiosurgery, a tracking method based on orthogonal real-time MRI planes was developed for AF treatments with an MRI-guided radiotherapy system. Four healthy volunteers underwent cardiac MRI of the LA. Contractile motion was quantified on 3D LA models derived from 4D scans with 10 phases acquired in end-exhalation. Three localization strategies were developed and tested retrospectively on 2D real-time scans (sagittal, temporal resolution 100 ms, free breathing). The best-performing method was then used to measure 3D target positions in 2D-2D orthogonal planes (sagittal-coronal, temporal resolution 200-252 ms, free breathing) in 20 configurations of a digital phantom and in the volunteer data. The 3D target localization accuracy was quantified in the phantom and qualitatively assessed in the real data. Mean cardiac contraction was ⩽ 3.9 mm between maximum dilation and contraction but anisotropic. A template matching approach with two distinct template phases and ECG-based selection yielded the highest 2D accuracy of 1.2 mm. 3D target localization showed a mean error of 3.2 mm in the customized digital phantoms. Our algorithms were successfully applied to the 2D-2D volunteer data in which we measured a mean 3D LA motion extent of 16.5 mm (SI), 5.8 mm (AP) and 3.1 mm (LR). Real-time target localization on orthogonal MRI planes was successfully implemented for highly deformable targets treated in cardiac radiosurgery. The developed method measures target shifts caused by respiration and cardiac contraction. If the detected motion can be compensated accordingly, an MRI-guided radiotherapy system could potentially enable completely non-invasive treatment of AF.

Technical Note: Experimental results from a prototype high-field inline MRI-linac.

PURPOSE: The pursuit of real-time image guided radiotherapy using optimal tissue contrast has seen the development of several hybrid magnetic resonance imaging (MRI)-treatment systems, high field and low field, and inline and perpendicular configurations. As part of a new MRI-linac program, an MRI scanner was integrated with a linear accelerator to enable investigations of a coupled inline MRI-linac system. This work describes results from a prototype experimental system to demonstrate the feasibility of a high field inline MR-linac. METHODS: The magnet is a 1.5 T MRI system (Sonata, Siemens Healthcare) was located in a purpose built radiofrequency (RF) cage enabling shielding from and close proximity to a linear accelerator with inline (and future perpendicular) orientation. A portable linear accelerator (Linatron, Varian) was installed together with a multileaf collimator (Millennium, Varian) to provide dynamic field collimation and the whole assembly built onto a stainless-steel rail system. A series of MRI-linac experiments was performed to investigate (1) image quality with beam on measured using a macropodine (kangaroo) ex vivo phantom; (2) the noise as a function of beam state measured using a 6-channel surface coil array; and (3) electron contamination effects measured using Gafchromic film and an electronic portal imaging device (EPID). RESULTS: (1) Image quality was unaffected by the radiation beam with the macropodine phantom image with the beam on being almost identical to the image with the beam off. (2) Noise measured with a surface RF coil produced a 25% elevation of background intensity when the radiation beam was on. (3) Film and EPID measurements demonstrated electron focusing occurring along the centerline of the magnet axis. CONCLUSIONS: A proof-of-concept high-field MRI-linac has been built and experimentally characterized. This system has allowed us to establish the efficacy of a high field inline MRI-linac and study a number of the technical challenges and solutions.

Development of a registration framework to validate MRI with histology for prostate focal therapy.

PURPOSE: Focal therapy has been proposed as an alternative method to whole-gland treatment for prostate cancer when aiming to reduce treatment side effects. The authors recently validated a radiobiological model which takes into account tumor location and tumor characteristics including tumor cell density, Gleason score, and hypoxia in order to plan optimal dose distributions for focal therapy. The authors propose that this model can be informed using multiparametric MRI (mpMRI) and in this study present a registration framework developed to map prostate mpMRI and histology data, where histology will provide the "ground truth" data regarding tumor location and biology. The authors aim to apply this framework to a growing database to develop a prostate biological atlas which will enable MRI based planning for prostate focal therapy treatment. METHODS: Six patients scheduled for routine radical prostatectomy were used in this proof-of-concept study. Each patient underwent mpMRI scanning prior to surgery, after which the excised prostate specimen was formalin fixed and mounted in agarose gel in a custom designed sectioning box. T2-weighted MRI of the specimen in the sectioning box was acquired, after which 5 mm sections of the prostate were cut and histology sections were microtomed. A number of image processing and registration steps were used to register histology images with ex vivo MRI and deformable image registration (DIR) was applied to 3D T2w images to align the in vivo and ex vivo MRI data. Dice coefficient metrics and corresponding feature points from two independent annotators were selected in order to assess the DIR accuracy. RESULTS: Images from all six patients were registered, providing histology and in vivo MRI in the ex vivo MRI frame of reference for each patient. Results demonstrated that their DIR methodology to register in vivo and ex vivo 3D T2w MRI improved accuracy in comparison with an initial manual alignment for prostates containing features which were readily visible on MRI. The average estimated uncertainty between in vivo MRI and histology was 3.3 mm, which included an average error of 3.1 mm between in vivo and ex vivo MRI after applying DIR. The mean dice coefficient for the prostate contour between in vivo and ex vivo MRI increased from 0.83 before DIR to 0.93 after DIR. CONCLUSIONS: The authors have developed a registration framework for mapping in vivo MRI data of the prostate with histology by implementing a number of processing steps and ex vivo MRI of the prostate specimen. Validation of DIR was challenging, particularly in prostates with few or mostly linear rather than spherical shaped features. Refinement of their MR imaging protocols to improve the data quality is currently underway which may improve registration accuracy. Additional mpMRI sequences will be registered within this framework to quantify prostate tumor location and biology.

Quantitative evaluation of diffusion-weighted imaging techniques for the purposes of radiotherapy planning in the prostate.

OBJECTIVE: Diffusion-weighted imaging (DWI) is an important technique for the localization of prostate cancer, and its response assessment during treatment with radiotherapy (RT). However, it has known limitations in terms of distortions and artefacts using standard acquisition techniques. This study evaluates two alternative methods that offer the promise of improved image quality and the potential for more reliable and consistent diffusion data. METHODS: Three DWI techniques were investigated; single-shot echoplanar imaging (EPI), EPI combined with reduced volume excitation (ZOOMit; Siemens Healthcare, Erlangen, Germany) and read-out segmentation with navigator-echo correction (RESOLVE; Siemens Healthcare). Daily measurements of apparent diffusion coefficient (ADC) value were made in a quality assurance phantom to assess the repeatability of each sequence. In order to evaluate the geometric integrity of these sequences, ten normal volunteers were scanned, and the prostate was contoured to compare its similarity with T2 weighted images. RESULTS: Phantom ADC values were significantly higher using the standard EPI sequence than those of the other two sequences. Differences were also observed between sequences in terms of repeatability, with RESOLVE and EPI performing better than ZOOMit. Overall, the RESOLVE sequence provided the best agreement for the in vivo data with smaller differences in volume and higher contour similarity than T2 weighted imaging. CONCLUSION: Important differences have been observed between each of the three techniques investigated with RESOLVE performing the best overall. We have adopted this sequence for routine RT simulation of prostate patients at Liverpool Cancer Therapy Centre. ADVANCES IN KNOWLEDGE: This work will be of interest to the increasing number of centres wanting to incorporate quantitative DWI in a clinical setting.

Radiotherapy beyond cancer: target localization in real-time MRI and treatment planning for cardiac radiosurgery.

PURPOSE: Atrial fibrillation (AFib) is the most common cardiac arrhythmia that affects millions of patients world-wide. AFib is usually treated with minimally invasive, time consuming catheter ablation techniques. While recently noninvasive radiosurgery to the pulmonary vein antrum (PVA) in the left atrium has been proposed for AFib treatment, precise target location during treatment is challenging due to complex respiratory and cardiac motion. A MRI linear accelerator (MRI-Linac) could solve the problems of motion tracking and compensation using real-time image guidance. In this study, the authors quantified target motion ranges on cardiac magnetic resonance imaging (MRI) and analyzed the dosimetric benefits of margin reduction assuming real-time motion compensation was applied. METHODS: For the imaging study, six human subjects underwent real-time cardiac MRI under free breathing. The target motion was analyzed retrospectively using a template matching algorithm. The planning study was conducted on a CT of an AFib patient with a centrally located esophagus undergoing catheter ablation, representing an ideal case for cardiac radiosurgery. The target definition was similar to the ablation lesions at the PVA created during catheter treatment. Safety margins of 0 mm (perfect tracking) to 8 mm (untracked respiratory motion) were added to the target, defining the planning target volume (PTV). For each margin, a 30 Gy single fraction IMRT plan was generated. Additionally, the influence of 1 and 3 T magnetic fields on the treatment beam delivery was simulated using Monte Carlo calculations to determine the dosimetric impact of MRI guidance for two different Linac positions. RESULTS: Real-time cardiac MRI showed mean respiratory target motion of 10.2 mm (superior-inferior), 2.4 mm (anterior-posterior), and 2 mm (left-right). The planning study showed that increasing safety margins to encompass untracked respiratory motion leads to overlapping structures even in the ideal scenario, compromising either normal tissue dose constraints or PTV coverage. The magnetic field caused a slight increase in the PTV dose with the in-line MRI-Linac configuration. CONCLUSIONS: The authors' results indicate that real-time tracking and motion compensation are mandatory for cardiac radiosurgery and MRI-guidance is feasible, opening the possibility of treating cardiac arrhythmia patients completely noninvasively.

Commissioning of a new wide-bore MRI scanner for radiotherapy planning of head and neck cancer.

OBJECTIVE: A combination of CT and MRI is recommended for radiotherapy planning of head and neck cancers, and optimal spatial co-registration is achieved by imaging in the treatment position using the necessary immobilisation devices on both occasions, something which requires wide-bore scanners. Quality assurance experiments were carried out to commission a newly installed 1.5-T wide-bore MRI scanner and a dedicated, flexible six-channel phased array head and neck coil. METHODS: Signal-to-noise ratio (SNR) and spatial signal uniformity were quantified using a homogeneous aqueous phantom, and geometric distortion was quantified using a phantom with water-filled fiducials in a grid pattern. Volunteer scans were also used to determine the in vivo image quality. Clinically relevant T1 weighted and T2 weighted fat-suppressed sequences were assessed in multiple scan planes (both sequences fast spin echo based). The performance of two online signal uniformity correction schemes, one utilising low-resolution reference scans and the other not utilising low-resolution reference scans, was compared. RESULTS: Geometric distortions, for a ±35-kHz bandwidth, were <1 mm for locations within 10 cm of the isocentre rising to 1.8 mm at 18 cm away. SNR was above 50, and uniformity in the axial plane was 71% and 95% before and after uniformity correction, respectively. CONCLUSION: The combined performance of the wide-bore scanner and the dedicated coil was adjudged adequate, although superior-inferior spatial coverage was slightly limited in the lower neck. ADVANCES IN KNOWLEDGE: These results will be of interest to the increasing number of oncology centres that are seeking to incorporate MRI into planning practice using dedicated equipment.

Quantitative comparison of 3D and 2.5D gamma analysis: introducing gamma angle histograms.

Comparison of dose distributions using the 3D gamma method is anticipated to provide better indicators for the quality assurance process than the 2.5D (stacked 2D slice-by-slice) gamma calculation, especially for advanced radiotherapy technologies. This study compares the accuracy of the 3D and 2.5D gamma calculation methods. 3D and 2.5D gamma calculations were carried out on four reference/evaluation 3D dose sample pairs. A number of analysis methods were used, including average gamma and gamma volume histograms. We introduce the concept of gamma-angle histograms. Noise sensitivity tests were also performed using two different noise models. The advantage of the 3D gamma method showed up as a higher proportion of points passing the tolerance criteria of 3% dose difference and 3 mm distance-to-agreement (DTA), with considerably lower average gamma values, a lower influence of the DTA criterion, and a higher noise tolerance. The 3D gamma approach is more reliable than the 2.5D approach in terms of providing comprehensive quantitative results, which are needed in quality assurance procedures for advanced radiotherapy methods.

The potential for an enhanced role for MRI in radiation-therapy treatment planning.

The exquisite soft-tissue contrast of magnetic resonance imaging (MRI) has meant that the technique is having an increasing role in contouring the gross tumor volume (GTV) and organs at risk (OAR) in radiation therapy treatment planning systems (TPS). MRI-planning scans from diagnostic MRI scanners are currently incorporated into the planning process by being registered to CT data. The soft-tissue data from the MRI provides target outline guidance and the CT provides a solid geometric and electron density map for accurate dose calculation on the TPS computer. There is increasing interest in MRI machine placement in radiotherapy clinics as an adjunct to CT simulators. Most vendors now offer 70 cm bores with flat couch inserts and specialised RF coil designs. We would refer to these devices as MR-simulators. There is also research into the future application of MR-simulators independent of CT and as in-room image-guidance devices. It is within the background of this increased interest in the utility of MRI in radiotherapy treatment planning that this paper is couched. The paper outlines publications that deal with standard MRI sequences used in current clinical practice. It then discusses the potential for using processed functional diffusion maps (fDM) derived from diffusion weighted image sequences in tracking tumor activity and tumor recurrence. Next, this paper reviews publications that describe the use of MRI in patient-management applications that may, in turn, be relevant to radiotherapy treatment planning. The review briefly discusses the concepts behind functional techniques such as dynamic contrast enhanced (DCE), diffusion-weighted (DW) MRI sequences and magnetic resonance spectroscopic imaging (MRSI). Significant applications of MR are discussed in terms of the following treatment sites: brain, head and neck, breast, lung, prostate and cervix. While not yet routine, the use of apparent diffusion coefficient (ADC) map analysis indicates an exciting future application for functional MRI. Although DW-MRI has not yet been routinely used in boost adaptive techniques, it is being assessed in cohort studies for sub-volume boosting in prostate tumors.

A method to produce and validate a digitally reconstructed radiograph-based computer simulation for optimisation of chest radiographs acquired with a computed radiography imaging system.

OBJECTIVES: The purpose of this study was to develop and validate a computer model to produce realistic simulated computed radiography (CR) chest images using CT data sets of real patients. METHODS: Anatomical noise, which is the limiting factor in determining pathology in chest radiography, is realistically simulated by the CT data, and frequency-dependent noise has been added post-digitally reconstructed radiograph (DRR) generation to simulate exposure reduction. Realistic scatter and scatter fractions were measured in images of a chest phantom acquired on the CR system simulated by the computer model and added post-DRR calculation. RESULTS: The model has been validated with a phantom and patients and shown to provide predictions of signal-to-noise ratios (SNRs), tissue-to-rib ratios (TRRs: a measure of soft tissue pixel value to that of rib) and pixel value histograms that lie within the range of values measured with patients and the phantom. The maximum difference in measured SNR to that calculated was 10%. TRR values differed by a maximum of 1.3%. CONCLUSION: Experienced image evaluators have responded positively to the DRR images, are satisfied they contain adequate anatomical features and have deemed them clinically acceptable. Therefore, the computer model can be used by image evaluators to grade chest images presented at different tube potentials and doses in order to optimise image quality and patient dose for clinical CR chest radiographs without the need for repeat patient exposures.

A method to optimize the processing algorithm of a computed radiography system for chest radiography.

A test methodology using an anthropomorphic-equivalent chest phantom is described for the optimization of the Agfa computed radiography "MUSICA" processing algorithm for chest radiography. The contrast-to-noise ratio (CNR) in the lung, heart and diaphragm regions of the phantom, and the "system modulation transfer function" (sMTF) in the lung region, were measured using test tools embedded in the phantom. Using these parameters the MUSICA processing algorithm was optimized with respect to low-contrast detectability and spatial resolution. Two optimum "MUSICA parameter sets" were derived respectively for maximizing the CNR and sMTF in each region of the phantom. Further work is required to find the relative importance of low-contrast detectability and spatial resolution in chest images, from which the definitive optimum MUSICA parameter set can then be derived. Prior to this further work, a compromised optimum MUSICA parameter set was applied to a range of clinical images. A group of experienced image evaluators scored these images alongside images produced from the same radiographs using the MUSICA parameter set in clinical use at the time. The compromised optimum MUSICA parameter set was shown to produce measurably better images.

Differentiation of benign and malignant sub-1 cm breast lesions using dynamic contrast enhanced MRI.

The purpose of this work is to assess the additional benefit of MRI-based morphology and quantification of contrast enhancement in the differential diagnosis of sub-1cm breast lesions. Forty-three women with suspected breast cancer were examined using X-ray mammography, ultrasound mammography, and MRI. Dynamic contrast imaging was performed and relative enhancement at various time-points was calculated. The dynamic data was also processed using a two-compartment pharmacokinetic model. Radiological interpretation of high-resolution post-contrast images revealed a similar accuracy (69%) compared to X-ray mammography (69%) and ultrasound mammography (67%). The best individual parameter calculated from the dynamic images was found to be the exchange rate constant which revealed a diagnostic accuracy of 0.74 +/- 0.08. When information from the post-contrast images and dynamic data was combined in a logistic regression model a diagnostic accuracy of 0.92 +/- 0.03 was achieved. In conclusion, MR imaging of small breast lesions is feasible and the incorporation of quantitative MR derived parameters is beneficial.

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS).

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS) is in progress. The study design, accrual to date, and related research projects are described. Revised accrual rates and expected recruitment are given. 15 cancers have been detected to date, from a total of 1236 screening measurements. This event rate and the tumour grades reported are compared with recent reports from other studies in women at high risk of breast cancer.

Comparison of quantitative T2 mapping and diffusion-weighted imaging in the normal and pathologic prostate.

In this study, diffusion-weighted images of the human prostate were successfully obtained, enabling quantification of apparent diffusion coefficients (ADCs) in normal and pathologic regions. A dual acquisition fast spin-echo sequence was used for accurate T2 calculation. T2 values were significantly higher in the peripheral zone than the central gland (P = 0.015). No significant correlations were found in either normal or pathologic tissue between ADC values and relaxation rates for all three gradient directions and the orientationally averaged water diffusion coefficient. Evidence suggesting that diffusional anisotropy is present in normal prostatic tissue is also detailed, with significant differences noted between the z-component and both the x- and y-components of the ADC for peripheral zone (P < 0.040) and central gland (P < 0.001).