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

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

Tissue mimicking materials for imaging and therapy phantoms: a review

Tissue mimicking materials (TMMs), typically contained within phantoms, have been used for many decades in both imaging and therapeutic applications. This review investigates the specifications that are typically being used in development of the latest TMMs. The imaging modalities that have been investigated focus around CT, mammography, SPECT, PET, MRI and ultrasound. Therapeutic applications discussed within the review include radiotherapy, thermal therapy and surgical applications. A number of modalities were not reviewed including optical spectroscopy, optical imaging and planar x-rays. The emergence of image guided interventions and multimodality imaging have placed an increasing demand on the number of specifications on the latest TMMs. Material specification standards are available in some imaging areas such as ultrasound. It is recommended that this should be replicated for other imaging and therapeutic modalities. Materials used within phantoms have been reviewed for a series of imaging and therapeutic applications with the potential to become a testbed for cross-fertilization of materials across modalities. Deformation, texture, multimodality imaging and perfusion are common themes that are currently under development

Selection of diagnostic features on breast MRI to differentiate between malignant and benign lesions using computer-aided diagnosis: differences in lesions presenting as mass and non-mass-like enhancement

Purpose: To investigate methods developed for the characterisation of the morphology and enhancement kinetic features of both mass and non-mass lesions, and to determine their diagnostic performance to differentiate between malignant and benign lesions that present as mass versus non-mass types. Methods: Quantitative analysis of morphological features and enhancement kinetic parameters of breast lesions were used to differentiate among four groups of lesions: 88 malignant (43 mass, 45 non-mass) and 28 benign (19 mass, 9 non-mass). The enhancement kinetics was measured and analysed to obtain transfer constant (Ktrans) and rate constant (kep). For each mass eight shape/margin parameters and 10 enhancement texture features were obtained. For the lesions presenting as nonmass-like enhancement, only the texture parameters were obtained. An artificial neural network (ANN) was used to build the diagnostic model. Results: For lesions presenting as mass, the four selected morphological features could reach an area under the ROC curve (AUC) of 0.87 in differentiating between malignant and benign lesions. The kinetic parameter (kep) analysed from the hot spot of the tumour reached a comparable AUC of 0.88. The combined morphological and kinetic features improved the AUC to 0.93, with a sensitivity of 0.97 and a specificity of 0.80. For lesions presenting as non-mass-like enhancement, four texture features were selected by the ANN and achieved an AUC of 0.76. The kinetic parameter kepfrom the hot spot only achieved an AUC of 0.59, with a low added diagnostic value. Conclusion: The results suggest that the quantitative diagnostic features can be used for developing automated breast CAD (computer-aided diagnosis) for mass lesions to achieve a high diagnostic performance, but more advanced algorithms are needed for diagnosis of lesions presenting as non-mass-like enhancement. © The Author(s) 2009

In Vivo Evaluation of the Presence of Bone Marrow in Cortical Porosity in Postmenopausal Osteopenic Women

This is the first observational study examining cortical porosity in vivo in postmenopausal osteopenic women and to incorporate data from two different imaging modalities to further examine the nature of cortical porosity. The goal of this study was to combine high-resolution peripheral computed tomography (HR-pQCT) images, which contain high spatial resolution information of the cortical structure, and magnetic resonance (MR) images, which allow the visualization of soft tissues such as bone marrow, to observe the amount of cortical porosity that contains bone marrow in postmenopausal osteopenic women. The radius of 49 and the tibia of 51 postmenopausal osteopenic women (age 56 ± 3.7) were scanned using both HR-pQCT and MR imaging. A normalized mutual information registration algorithm was used to obtain a three-dimensional rigid transform which aligned the MR image to the HR-pQCT image. The aligned images allowed for the visualization of bone marrow in cortical pores. From the HR-pQCT image, the percent cortical porosity, the number of cortical pores, and the size of each cortical pore was determined. By overlaying the aligned MR and HR-pQCT images, the percent of cortical pores containing marrow, the number of cortical pores containing marrow, and the size of each cortical pore containing marrow were measured. While the amount of cortical porosity did not vary greatly between subjects, the type of cortical pore, containing marrow vs. not containing marrow, varied highly between subjects. The results suggest that cortical pore spaces contain components of varying composition, and that there may be more than one mechanism for the development of cortical porosity

Neoadjuvant chemotherapy in breast cancer: early response prediction with quantitative MR imaging and spectroscopy.

A prospective study was undertaken in women undergoing neoadjuvant chemotherapy for locally advanced breast cancer in order to determine the ability of quantitative magnetic resonance imaging (MRI) and proton spectroscopy (MRS) to predict ultimate tumour response (percentage decrease in volume) or to detect early response. Magnetic resonance imaging and MRS were carried out before treatment and after the second of six treatment cycles. Pharmacokinetic parameters were derived from T1-weighted dynamic contrast-enhanced MRI, water apparent diffusion coefficient (ADC) was measured, and tissue water:fat peak area ratios and water T2 were measured using unsuppressed one-dimensional proton spectroscopic imaging (30 and 135 ms echo times). Pharmacokinetic parameters and ADC did not detect early response; however, early changes in water:fat ratios and water T2 (after cycle two) demonstrated substantial prognostic efficacy. Larger decreases in water T2 accurately predicted final volume response in 69% of cases (11/16) while maintaining 100% specificity and positive predictive value. Small/absent decreases in water:fat ratios accurately predicted final volume non-response in 50% of cases (3/6) while maintaining 100% sensitivity and negative predictive value. This level of accuracy might permit clinical application where early, accurate prediction of non-response would permit an early change to second-line treatment, thus sparing patients unnecessary toxicity, psychological morbidity and delay of initiation of effective treatment

Ageing, adipose tissue, fatty acids and inflammation

A common feature of ageing is the alteration in tissue distribution and composition, with a shift in fat away from lower body and subcutaneous depots to visceral and ectopic sites. Redistribution of adipose tissue towards an ectopic site can have dramatic effects on metabolic function. In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Additionally, the risk of developing cardiovascular disease is increased with elevated visceral adipose distribution. In ageing, adipose tissue becomes dysfunctional, with the pathway of differentiation of preadipocytes to mature adipocytes becoming impaired; this results in dysfunctional adipocytes less able to store fat and subsequent fat redistribution to ectopic sites. Low grade systemic inflammation is commonly observed in ageing, and may drive the adipose tissue dysfunction, as proinflammatory cytokines are capable of inhibiting adipocyte differentiation. Beyond increased ectopic adiposity, the effect of impaired adipose tissue function is an elevation in systemic free fatty acids (FFA), a common feature of many metabolic disorders. Saturated fatty acids can be regarded as the most detrimental of FFA, being capable of inducing insulin resistance and inflammation through lipid mediators such as ceramide, which can increase risk of developing atherosclerosis. Elevated FFA, in particular saturated fatty acids, maybe a driving factor for both the increased insulin resistance, cardiovascular disease risk and inflammation in older adults

Functional MRI for quantitative treatment response prediction in locally advanced rectal cancer

Despite advances in multimodality treatment strategies for locally advanced rectal cancer and improvements in locoregional control, there is still a considerable variation in response to neoadjuvant chemoradiotherapy (CRT). Accurate prediction of response to neoadjuvant CRT would enable early stratification of management according to good responders and poor responders, in order to adapt treatment to improve therapeutic outcomes in rectal cancer. Clinical studies in diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI have shown promising results for the prediction of therapeutic response in rectal cancer. DWI allows for assessment of tumour cellularity. DCE-MRI enables evaluation of factors of the tumour microvascular environment and changes in perfusion in response to treatment. Studies have demonstrated that predictors of good response to CRT include lower tumour pre-CRT apparent diffusion coefficient (ADC), greater percentage increase in ADC during and post CRT, and higher pre-CRT Ktrans. However, the mean ADC and Ktrans values do not adequately reflect tumour heterogeneity. Multiparametric MRI using quantitative DWI and DCE-MRI in combination, and a histogram analysis technique can assess tumour heterogeneity and its response to treatment. This strategy has the potential to improve the accuracy of therapeutic response prediction in rectal cancer and warrants further investigation

ACE : architecture, city and environment

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