Volume 36, Issue 6, June 2009
Index of content:
- Joint Imaging/Therapy Symposium: Ballroom C
Imaging as a Biomarker
36(2009); http://dx.doi.org/10.1118/1.3182335View Description Hide Description
There is an increasing trend towards more individualized, targeted cancer therapy. This places new demands for tools to help guide treatment selection and evaluate early response to the selected therapy. While cancer treatment selection has traditionally depended on tissue‐based biomarkers, functional and molecular imaging can play an important and complementary role in directing targeted cancer therapy and monitoring early response. Imaging has several capabilities distinct from tissue sampling and assay, including the ability to measure the heterogeneity of target expression and to characterize in vivo pharmacodynamics. The use of molecular imaging to direct cancer therapy departs from the traditional role of cancerimaging to detect and localize cancer sites. This implies an expansion of the scope of cancerimaging from detection methods that rely on features such as aberrant glycolysis that are present in tumors but not in normal tissues, to a broader approach using imaging to quantify in vivo phenotype. In the latter case, the absence of a particular tumor feature, such as a target receptor, may be as important as its presence. The need to simultaneously localize and characterize tumor sites places an emphasis on multi‐modality imaging such as PET/CT or multiple PET images using combinations of different imaging probes. This talk will review applications of molecular imaging to targeted cancer therapy for clinical trials and clinical practice, focusing mostly on PET. Examples using molecular imaging to (1) predict tumor clinical behavior, (2) identify therapeutic targets, (3) predict therapeutic resistance, and (4) evaluate early response to therapy will be shown. The theme of the presentation will be that quantitative in vivo measures of tumor phenotype using imaging are complementary to in vitro assay in directing targeted, individualized cancer therapy.
1. Describe ways in which molecular imaging can help direct cancer therapy.
2. Discuss the complementary role of in vitro assay and in vivo imaging in measuring cancer phenotype.
3. List examples of how imaging can be used to help direct cancer therapy.
36(2009); http://dx.doi.org/10.1118/1.3182336View Description Hide Description
Imaging biomarkers are increasingly used as primary or secondary endpoints in therapeutic trials. There are many academic units, professional organizations, industry groups and federal agencies addressing one or more components or issues associated with imaging biomarkers, and communication and coordination of efforts has been minimal. The RSNA has organized an Imaging Biomarkers Roundtable to establish ongoing communication among these organizations, and to develop a roadmap of activities and goals.
Validation of imaging methods as biomarkers is complicated by the variability within and between patients, by the human observer component, by the variability across imaging devices from different manufacturers, and by the need to standardize methods across institutions and centers. To understand the errors and reduce them where possible, the Quantitative Imaging Biomarkers Alliance (QIBA) has been formed. These and other efforts are active and productive. Accomplishments and future plans will be discussed.
1. Understand efforts to integrate imaging biomarkers in clinical trials.
2. Understand efforts to improve the accuracy and precision of imaging biomarkers.
36(2009); http://dx.doi.org/10.1118/1.3182337View Description Hide Description
The Science Council (SC) of the AAPM has initiated the Quantitative Imaging (QI) Initiative, which is an effort focused on moving the field of diagnostic imaging towards a more quantitative footing. While much of the quantitative content of the radiologist report will be generated by the radiologist with perhaps the help of user‐friendly and robust software capable of generating quantitative metrics off of a patient's images, there is an important role for physicists to play in assuring the quantitative integrity of the image data. The QI Initiative currently has three task groups, on PET/CT, on dynamic contrast enhanced MRI, and on CT. The methods and activity of these groups towards achieving their objectives will be discussed. The activity of these three groups has overlap with similar efforts of other societies such as the SNM, ISMRM, and the RSNA, and the interconnections will also be described. The parallel, integrated efforts towards creating a more quantitative future for medical imaging assessment is being driven by the needs of clinical research trials, as well as other payer initiatives such as pay for performance. Long term, the QI Initiative will include a comprehensive array of procedures to reduce variance in the imaging process, by standardization of the acquisition protocols, calibration of the spatial and gray scale output of scanners, incorporation of structured reporting tools to improve accuracy and format consistency, and the development of scientific software capable of extracting accurate QI data from image data.
36(2009); http://dx.doi.org/10.1118/1.3182524View Description Hide Description
The exquisite soft tissue contrast, 3D imaging capability, and lack of radiationdose brings magnetic resonance imaging into consideration for guiding external beam radiation therapy of thoracic and abdominal tumors which undergo significant intrafraction motion. For example, in the case of lung cancer, which accounts for 13% of radiation therapy recipients, tumors may move on the order of 20 mm at a rate of 10 mm/s. MRI is ideally suited to continuously monitor the geometry of the tumor for real‐time modification to the treatment protocol. However, there are technical challenges to integrating a radiation therapy system into an MRI system. In this talk, we discuss the considerations for the MRI system in MR‐guided radiotherapy.
For the MRI system geometry, several MR systems have been proposed that vary in field strength and system geometry. In the evaluation of these geometries, consideration should include system performance and requirements. Deviation from the conventional cylindrical MRI system affects the field strength, gradient performance, and magnetic field homogeneity. Even with a given magnet geometry, there are tradeoffs in the imaging choices that can be made. Since the signal‐to‐noise ratio is proportional to the field strength, the voxel volume, and the square root of the acquisition time, the voxel volume can be traded off for temporal resolution. Different pulse sequences have different inherent contrasts and signal levels. All of these affect the ability to perform the imaging task, but must be considered within the context of the goal to localize the boundary of the tumor target with sufficient temporal and spatial resolution.
Other system considerations might include the use of radiation transparent RF coils. Another consideration is the effect on the MRI of other equipment. High magnetic susceptibility metals such as iron, steel, and many stainless steels experience large forces that would pull them into the MRI system. Lower magnetic susceptibility metals such as aluminum and lead can be safely used within the MRImagnetic field, although care must be taken to minimize eddy currents that may be induced in them, as this may affect imaging performance.
1. Understand the tradeoffs in imaging capabilities with different MRI system geometries
2. Understand the tradeoffs in MRimaging of tumors for real‐time therapy guidance
36(2009); http://dx.doi.org/10.1118/1.3182525View Description Hide Description
The high magnetic field associated with magnetic resonance imaging complicates the design and engineering of combined MRI‐radiation therapy systems due to the potential interactions between the magnetic field and the electron beam of the accelerator, together with the converse problem of perturbation of the MRImagnetic field by ferromagnetic materials in the structure of the accelerator system. Addressing these issues increases the cost and complexity of a combined system. Hence the need for a high magnetic field is generally viewed as a disadvantage by radiation physicists or, at best, as a necessary price to pay for imaging with MRItissue contrast.
However, the effects of the magnetic field on the radiation therapy delivery system are not uniformly negative and it has been proposed that the magnetic field may be turned to advantage in reducing the secondary electrondose to the skin. It has also been hypothesized that it may be practical to utilize an appropriately oriented magnetic field to improve the dose distribution within the patient by reducing the penumbra of secondary electrons around the beam and, possibly, to provide a sharper cut‐off of the deposited dose downstream of the treatment region. If this can be done effectively it could furnish a proton‐like Bragg peak from an x‐ray treatment beam
If a magnetic field is present in the volume of the lesion during treatment, the trajectories of the secondary electrons and positrons generated by the interaction of the high energy X‐ray beam with tissue, are known to be perturbed. J.J.W. Langendijk and coworkers have modeled this in terms of its effect on treatment planning.
This paper reports work carried out using the EGS 5 Monte Carlo code, (which can incorporate both electric and magnetic fields), to model the dose distributions obtained in tissue with various magnetic field orientations and strengths, using typical Clinac X‐ray spectra. The following sub topics are addressed:
1. The magnitude of the effect of the magnetic field in different tissue types is computed. 2. The practicality of this approach for modifying dose distribution is assessed, based upon the magnetic field strength and magnetic field conformations that are required.
A portion of the research reported here was funded by Varian Medical Systems.
36(2009); http://dx.doi.org/10.1118/1.3182526View Description Hide Description
There has been increased interest in developing real‐time MR‐guided radiotherapy systems because of the potential of 3D imaging in real time with the improved soft‐tissue contrast provided by MR. An overview of the issues related to the integration of a radiotherapy source (e.g. linac) with a low field magnetic system are discussed. The effects of the MRmagnetic fields on radiation treatment plans for the various generic designs, and on the performance of the linac are presented. The effects of radio frequency fields from the linac upon the MR image acquisition process is introduced. Advantages of low fields are discussed: minimization of the magnetic field‐induced distortions on plans; use conventional RTP instead of Monte Carlo for high fields; avoidance of hot/cold radiation spots at air‐tissue interfaces seen with high fields; reduced susceptibility artifacts; reduced geometric distortions; reduced magnetic shielding issues; exploitation of the increased T1 contrasts at low fields for fast imaging. The main disadvantage at low fields is decreased SNR. Some proposed designs are given. In particular, the first reported successful system providing any MRimaging during radiotherapy irradiation is discussed. This head prototype involves a 6 MV linac mounted onto an opening of a biplanar 0.2 T MR system. The linac‐MR gantry would rotate together to the prescribed angle of irradiation delivery. The only observable difference between the MRimages obtained with linac‐radiation ON to linac OFF is the small changes in SNR. Other possible enhancements (replacing low field with high field MR if required, different types of magnets, etc) to the generic design are also given.
The lecture will offer an overview of the advantages and disadvantages of low field MR for real‐time MR‐guided radiotherapy (with the introduction of a working prototype).
1. Understand the technical issues in integrating an MR system with a radiotherapy source, especially with a linac
2. Understand the issues related to distortions of the characteristics of dose deposition because of the MRmagnetic field
3. Understand the imaging advantages of low field MR, as well as, its disadvantage
4. Understand the technical advantages in the integration of low field system with a linac
5. Understand the advantages/disadvantages of the different generic designs proposed to date
36(2009); http://dx.doi.org/10.1118/1.3182527View Description Hide Description
At the UMC Utrecht, the Netherlands we have constructed a prototype MRI accelerator. The design is a 6 MV Elekta (Crawley, U.K.) Compact accelerator combined with a modified 1.5 T Philips Achieva (Best, The Netherlands) MRI system. The systems run according to our specifications. The simultaneous operation is shown by performing diagnostic quality 1.5 T MRI with the radiation beam on. As designed the interference between the two systems is completely suppressed, no interference was found.
The integrated 1.5 T MRI system and radiotherapy accelerator allow simultaneous irradiation and MR imaging. Both systems operate independent and no synchronization is required. The full diagnostic imaging capacities of the Philips MRI can be used, dedicated sequences for MRI guided radiotherapy treatments will be developed.
This proof of concept opens the door towards a clinical prototype to start testingMRI guided Radiotherapy (MRIgRT) in the clinic.
Acknowledgements: Both Elekta and Philips participate in this research program