Index of content:
Volume 34, Issue 6, June 2007
- Joint Imaging/Therapy Symposium: Room M100F
- Imaging for TherapyAssessment
34(2007); http://dx.doi.org/10.1118/1.2761549View Description Hide Description
In vivobiomedical imaging for assessment of therapeutic response is becoming an increasingly important field. Early assessment and prediction of treatment response allow for individualized re‐optimization of therapy, which represents a novel concept and a paradigm shift from conventional clinical trials. Recent Phase I/II trials have shown that biomedical imaging, including CT,MRI, PET, can provide an indication of therapeutic response, and possibly prior to the radiographic changes. In vivobiomedical imaging for assessment of therapeutic response is a dynamic and fast growing field. Many new trials are ongoing or in the design phase. The complicity of imaging technologies provides an opportunity for more AAPM members to engage in either single center trials or multi‐center trials in coming years. This symposium will provide overviews on PET/SPECT, MRI/MRS and the integration of multimodality imaging in clinical trials for assessment of treatment response.
The objectives of this symposium are:
1. What imaging modalities have shown potential value in phase I/II trials for assessment of therapeutic responses;
2. What are the advantages and limitations of using in vivo functional and metabolic imaging in clinical trials compared to conventional paradigms;
34(2007); http://dx.doi.org/10.1118/1.2761552View Description Hide Description
Treatment responses and late normal tissue injury are conventionally assessed months or years after the completion of therapy by standard clinical endpoints, such as local progression free survival or late fibrosis. This conventional paradigm presents two major weaknesses. First, at the time of the treatment outcomes being determined, it is often too late to change the outcome of patients. Secondly, takes a large number of patients and a long time to determine the efficacy of the tested treatment. It is urgent for clinical scientists to change this conventional paradigm and to assess the therapeutic response early, i.e. prior to the end of planned therapy. For early assessment of therapeutic responses, conventional clinical endpoints are no longer adequate. Functional, metabolic, and molecular imaging could provide a means or a marker for early assessment of normal tissue injury or of treatment responses prior to anatomic measurements of disease progression, thereby permitting re‐optimization of individual patient treatment strategies. This lecture will provide examples how to integrate multi‐modality imaging in clinical trials for early assessment of treatment response and normal tissue toxicity. The implications of the results will also be discussed.
1. Understand the time courses of response and toxicity.
2. Appreciate windows of opportunity for early assessment.
3. Introduce clinical trial design issues for early assessment.
- Technical and Clinical Challenge for In‐Room Target Localization
34(2007); http://dx.doi.org/10.1118/1.2761225View Description Hide Description
In‐room radiolographic imagingsystems is being rapidly implemented in routine clinical operations for target localization. A typical system consists of a kV x‐ray source and an amorphous‐silicon flat panel detector mounted orthogonally to the MV‐beam axis. The available clinical imaging capabilities from this configuration are 2‐D radiographic or fluoroscopic imaging and 3‐D CBCT. These techniques may have potential limitations either on not sufficient anatomical information for positioning verification (such as 2‐D technology) or long imaging time (several breathing cycles), mechanical constraints, and excessive dose to the imaging volume (such as CBCT technology). Therefore, limited‐angle digital tomosynthesis (DTS) is being investigated as an alternative 3‐D imaging technique. Much of the investigations have been focused on the clinical feasibility and efficacy of using DTS for on‐board target localization and comparison between DTS technology with 2‐D radiographic and CBCT technologies. This talk will summarize emerging clinical research to develop the DTS technology for on‐line patient positioning and target localization for image guided radiation therapy, specifically for anatomical sites of head and neck, abdomen, breast and prostate.
1. Brief review of DTS imaging technique in the treatment room.
2. Clinical feasibility and efficacy of using DTS for in‐room target localization.
34(2007); http://dx.doi.org/10.1118/1.2761226View Description Hide Description
Image guidance is particularly important in the delivery of external beam radiotherapy for localized prostate cancers because of a demonstrated need for high doses and the increasing interest in hypofractionated regimens. With small field radiation , the impact of inter‐ and intra‐fraction motion and deformation needs to be understood, ideally in individual patients rather that in a population. Multiple imaging and localization techniques are currently available to implement in therapy rooms. Each technique has a particular ability to address the motion and deformation issues. More importantly, the planning and dosimetric impact of such motion and deformation is only starting to be evaluated. Such dosimetric evaluations will be crucial in assessing the adequacy of individual techniques.
Current in‐room localization techniques are almost exclusively geared towards imaging prior to treatment, determining target offsets, and modifying the target position by moving the treatment table. It is clear that external marks and bony anatomy are poor proxies for determining the location of the prostate gland. Transabdominal ultrasound is an efficient method of performing daily image guidance, however it suffers from significant interuser variability. Implanted metallic fiducials significantly decrease the interuser variability and have been demonstrated to be stable within the prostate gland, therefore acting as adequate surrogates for prostate position. However, although practically extremely rare, significant deformation in poorly placed markers can result in anatomical changes that could render the markers suboptimal surrogates for prostate anatomy as a whole. Finally, volumetric imaging with different in‐room CT options (cone beam or helical kV or MV CT scanning) adds the ability of assessing entire volumes rather than individual points. However, practical consideration coupled with sometimes difficult interpretation of soft tissueimages makes the presence of fiducials still desirable. The main advantage of CTimaging is the potential for the evaluation of delivered dose variations in target and normal tissues. Finally, technologies such as electromagtnetic tracking enable the real‐time tracking of the location of the prostate throughout the treatment delivery. Such technologies will enable the therapists to interrupt the delivery and realign the target areas.
The clinical processes associated with each imaging technique are different and require different skills, possibly also resulting in different targeting solutions in individual patients. In the absence of actual clinical outcomes in the short term future, these processes will have to be evaluation on their technical merits. However, the accumulation of clinical outcome data (tumor control and toxicity) is crucial in understanding the true impact of these techniques.
1. Review the different technologies used for target localization in the pelvis.
2. Discuss the dosimetric impact of observations made with pelvic target localization during radiation therapy.
3. Discuss the future potential applications of image guidance and adaptive radiotherapy in the treatment of pelvic malignancies, particularly prostate cancers.
Research sponsored by Tomotherapy Inc., BrainLAB, and Calypso Medical corporations.
34(2007); http://dx.doi.org/10.1118/1.2761227View Description Hide Description
There has been significant progress in the technical delivery of radiation therapy in GI cancer. These innovations have included the use of intensity modulated radiation therapy,image guidance radiation therapy, and stereotactic radiation therapy. One of the key goals is judicious use of this technology. This lecture will highlight current efforts as well as future avenues of clinical research in the use of sophisticated radiationdelivery in the treatment of GI malignancies.
34(2007); http://dx.doi.org/10.1118/1.2761228View Description Hide Description
New in‐room IGRT techniques for treatment of targets in and around the lungs allow margin reduction compared to the use of more traditional MV radiographic verification techniques. Unlike targets in the head & neck, liver or prostate, the lung is interesting in that tumors are frequently easily visualized so that the use of surrogates is not always necessary. This is particularly true for volume imaging devices that can produce thin sections through the patient in various different orientations. These devices include diagnostic quality helical CT scanners placed in the treatment room in close proximity to the treatment unit as well as various MV or kV Computer Tomography approaches that use the capabilities of or simply attach to the treatment unit structure. Devices that use kV photons to produce dual stereoscopic 2D views of the patient do not allow such easy visualization of lesions in the lungs, but they are extremely helpful when reliable anatomic surrogates can be identified, or when fiducial markers can be surgically placed to identify the target position.
Hypofractionated dose schedules are gaining popularity for treatment of some early diagnosed non‐small cell lungcancers. Treating these tumors to a high dose in just a few fractions is challenging in that field placement is critical. In‐room IGRT has played an important role in positioning these treatment fields with the required accuracy. Treating the breast, another structure in the thorax region, presents a somewhat different challenge in that this part of the patient's anatomy is hard to reproducibly position for each day of treatment. In‐room IGRT can also be used to advantage to treat this structure. This is particularly true for the boost portion of the treatment.
Treating in or near the thorax is complicated by the fact that targets can move as a result of respiratory and/or cardiac motion. When breath hold, abdominal compression to damp a tumor's trajectory, target tracking, or treatment unit gating techniques are employed to control the effects of respiratory motion, using IGRT to verify patient positioning prior to treatment will not necessarily guarantee acceptable tumor targeting during dose delivery. However, the use of real time in‐room kV and MV fluoroscopy can provide extra information that is useful for this level of verification.
Using the new IGRT techniques does not assure that apertures are correct in terms of either their shape or orientation. Thus, it is important to combine the new IGRT techniques with the older standard approach. That is, portal imaging using the MV beam and treatment apertures remains an important step in the overall QA process.
1. To understand the design, functioning, advantages, and limitations of the different IGRT systems used for treating in and around the thorax region.
2. To understand how different IGRT systems can be used to provide the information needed to target moving lesions in the thorax region.
3. To understand the workflow issues for IGRT used to treat targets in the thorax.
34(2007); http://dx.doi.org/10.1118/1.2761229View Description Hide Description
Daily target localization is a critical step to ensure accurate delivery of 3‐D conformal radiation therapy and intensity‐modulated radiation therapy. Current in‐room localization technologies for HN and CNStreatment include 2D kilovoltage (kV) or megavoltage (MV) radiography,CT on‐the‐rail, cone beam CT(CBCT), megavoltage CT (MVCT), and optical guidance systems.
This lecture will provide an overview of the current in‐room target localization technologies for HN/CNS treatment, including the system design and characteristics, patient alignment process, and their integrations in clinical workflow. The accuracies of these technique and consequently the margin considerations will be discussed.
1. Understand the latest commercial available in‐room localization techniques for HN treatment.
2. Understand the accuracies of these localization systems.
3. Understand the margin considerations associated with using these systems.
- The John S. Laughlin Science Council Research Symposium: Quantitative Imaging for Cancer Diagnosis, Treatment, and Response Assessment
34(2007); http://dx.doi.org/10.1118/1.2761342View Description Hide Description
Purpose: To describe the novel design of the coupling an of MRI to a medical linac to provide real‐time tracking of the tumor and healthy tissues during irradiation by the treatment beam Method and Materials: Various embodiments are defined in our patents (Fallone, Carlone, Murray) to avoid mutual interference between the MR and the linac. Our method allows rotation of a linac with respect to the subject to allow irradiation of the subject from any angle without disturbing the magnet homogeneity. Magnetic shielding of the linac prevents disturbance from the MRI. RF signal shielding, modifications the RF‐signal triggering and pulse shaping are used to minimize linac interference of MRI RF read sequences. Various Monte Carlo calculations (EGS4 NRC and Penelope) and finite‐element analyses (Comsol) are performed in all design stages. Results: The initial design for the human system involves a bi‐planar MRI with 65 cm opening to allow rotation of the shoulders within the bore. A short 6 MV waveguide is coupled to one open end of the MR, and a beam‐stop and a projection imaging device (eg, flatpanel) is coupled to the other end. Rotation is provide by two concentric rings, and the permanent‐magnet design is preferred in the initial stage to provide stability and lack of electric wiring in the rotation process. Low fields allows very small fringe fields to minimize linac interference yet with adequate image quality of soft tissue for lungs, prostate, GBM, etc. Mutual interference issues and other issues arising externally are calculated and resolved. Conclusion: We have shown the design to be a practical, viable and realizable within a reasonable time frame. Our other presentations detail resolutions to mutual MRI‐linac interferences.
TU‐C‐M100F‐02: Quantification of Global Changes in Normal Appearing Brain Tissue of Cerebral Tumor Patients During Early‐Delayed Phase After Radiation Therapy34(2007); http://dx.doi.org/10.1118/1.2761343View Description Hide Description
Purpose:Radiation therapy (RT) affects the central nervous system manifesting in neurological complications. The aim was to quantitatively assess early‐delayed changes in normal‐appearing braintissue (NAT) ensuing RT using diffusiontensorimaging (DTI). We hypothesize that there are diffuse changes in NAT with degradation in structural integrity due to radiation. Methods: Twenty‐five patients with cerebral tumor (17 men, 8 women, median age 60 years) participated in IRB approved clinical MRI studies. Temporal changes in NAT were studied pre‐RT, 3‐ and 6‐weeks during RT, and post RT at ten‐, and 19‐weeks from start of RT. RT doses ranged from 50 to 81Gy. The DTI indices of fractional anisotropy (FA), mean diffusivity 〈D〉, eigen‐diffusivities parallel (λ∥) and perpendicular (λ⊥) to axonal fibers, of water diffusion were calculated on a voxel‐by‐voxel basis from DTI. Normal braintissue, excluding tumor and cerbero‐spinal‐fluid was categorized into two volumes of interest, either ipsilateral or contralateral to tumor hemisphere. Temporal changes in DTI indices were expressed as percentages. For example, percent change in FA during third week of RT is expressed as = 100*[(FAt=3week − FAt=Pre‐RT)/ FAt=Pre‐RT]. Results: There were significant changes in DTI indices after completion of RT in both the ipsilateral and contralateral NAT. Post RT at 19‐weeks, there was 10% increase in λ∥, 15% increase in λ⊥, 13% increase in 〈D〉, and 13% decrease in FA. The λ⊥ increase was 1.5 times that of λ∥. Magnitude of change was higher in ipsilateral compared to contralateral, with ipsilateral changes assuming significance earlier. However, contralateral changes tended to approach those of ipsilateral at 19‐weeks. Conclusions: Significant and gradual increases in eigen‐diffusivities indicate degradation of structural integrity. Changes in ipsilateral and contralateral hemispheres during and post RT signify diffuse bilateral structural degradation. Spatio‐temporal radioresponses noted herein emphasize minimizing dose to critical CNS structures and pathways.
34(2007); http://dx.doi.org/10.1118/1.2761344View Description Hide Description
Purpose: To develop and test a transurethral ultrasound therapy system which uses quantitative real‐time MRI temperature feedback to control the shape of the coagulated region within the prostate while sparing surrounding structures from thermal damage. Method and Materials: An MRI‐compatible transurethral heating applicator comprised of planar ultrasound transducers that produce a directional heating pattern has been constructed. This device is rotated within a 1.5T MR imager to distribute energy to targeted regions of the prostate by an MRI‐compatible motor, concurrent with imaging. The region of the prostate to be treated is selected based on MR imaging information. Subsequent heating is controlled by MRI temperature images acquired every 5s and a complete prostate volume can be coagulated with a single rotation in about 20m. In‐vivo experiments have been performed in a canine model and the spatial accuracy of the coagulation patterns has been assessed using contrast‐enhanced MR images and a novel, quantitative whole‐mount histology technique with image registration to the MR temperature maps. Results: Sufficient spatial resolution and temperature accuracy can be obtained at 1.5T to provide accurate feedback control of the coagulation pattern within ±1.5mm of the targeted heating radius. Histological analysis indicates that, under these treatment conditions, the margin between completely coagulated tissue and apparently undamaged tissue is ⩽3mm in this acute assay. These histological boundaries, when registered carefully with the quantitative MRI temperature histories, provide a good estimate of the temperature threshold (54.6±1.7°C) for complete coagulation. The contrast‐enhanced MR images clearly show the coagulated region but register less accurately with the histological boundaries. Conclusion: Successful control of transurethral ultrasound therapy using quantitative, real‐time MRI temperature images has been demonstrated in vivo. This technology offers good potential for an effective treatment for localized prostate cancer with reduction in morbidity.
34(2007); http://dx.doi.org/10.1118/1.2761345View Description Hide Description
Purpose:Contrast uptake behavior measured by dynamic contrast enhanced (DCE) MR has been shown to have diagnostic value for breast cancer. This paper is to show the feasibility of DCE breast cone beam CT(CBCT) for quantification of dynamic contrast uptake using a baseline and a single contrast enhanced CBCT.Method and Materials: A novel algorithm is proposed to determine the contrast uptake behavior for breast CBCT with a baseline image followed by a contrast enhanced acquisition synchronized with contrast injection. The method is based on the assumption that the contrast uptake curve in every voxel of the volume has a washin and a washout phase governed by a 3‐parameter equation, and the baseline along with the contrast enhanced projections are used to solve for these 3 parameters in each voxel. A computer simulation was performed based on functional CT data of cervix patients to evaluate the feasibility of the method to estimate different contrast uptake shapes. A phantom study was also done in a breast phantom with flow mechanism to compare the method against clinical CT for a fast washout and a plateau contrast uptake curve. Results: The computer simulation showed excellent accuracy of uptake characteristics for the new method that the DCE‐CBCT algorithm correctly determined the contrast uptake behavior in 14 out of 15 patients. Good agreement was also found in the phantom study in which both uptake curves (rapid washout and plateau) were accurately determined by the DCE‐CBCT method compared to those measured with clinical CT, although the former curves are more dispersed. Conclusions: Preliminary simulation and phantom data suggest the feasibility of the proposed method to determine different contrast uptake behavior in contrast enhanced breast CBCT which might have a potential for diagnosis of breast cancer.
TU‐C‐M100F‐05: Automated Classification of Substructures of White Matter Via Anisotropic Water Diffusion34(2007); http://dx.doi.org/10.1118/1.2761346View Description Hide Description
Purpose:Diffusiontenorimaging (DTI) has been shown to be a valuable technology for in vivo assessment of white matter (WM) diseases, and has potential for monitoring the effect of radiation on WM structures. The aim of this work is to develop an automated method for classification of substructures of normal‐appearing and disease‐affected white matter (NA and DAWM) from diffusiontenorimages. Methods: The methodology is based upon the fuzzy c‐means clustering algorithm with nearest‐neighbor spatial constraint to enhance spatial continuity and overcome intensity inhomogeneity. To resolve substructures of WM and grey matter (GM), which are obscured by large diffusion coefficients and variations in cerebral‐spinal fluid (CSF), a two‐layer hierarchical tree of fuzzy classification was developed. In the first level of classification, tissue is segmented from CSF or a fluid‐like class. Then, tissue is further partitioned into subclasses based upon their characteristicanisotropic water diffusion. We tested which feature space could result in better classification, in which the DTI data were presented as diffusion‐weighted data, elements of the diffusiontenor, and eigen‐diffusivities. We applied the method to DTI data from patients with normal‐appearing WM, low grade glioma, meningioma, and benign brain tumors. Resolved structures of NAWM and GM were compared to a brain atlas. Results: Eigen‐diffusivities resulted in most robust classification of substructures than other forms of data. Resolved substructures included genu and splenium of corpus callosum, corticospinalfibers, subinsular WM, optical radiation WM, internal capsule, caudate nucleus, lenticular nucleus, and thalamus. Necrotic tumor and edema regions of WM were identified with either a fluid‐like or sub‐tissue class, depending upon the water content, and viable tissue.Conclusion: We have developed a robust method for classification of substructures of NA and DA WM and GM using DTI. The differentiated substructures could be useful for radiation treatment planning, and for monitoring radiation effect.
34(2007); http://dx.doi.org/10.1118/1.2761347View Description Hide Description
Purpose: The purpose of this study was to develop and test a novel model for actively predicting the tumor's size, location, and mass while the patient is undergoing radiation therapy. Given that local failure represents the most common mode of failure for lungcancer, the ability to predict changes in the size and mass of the residual tumor mass has a high level of clinical significance. By predicting the tumor's future behavior, it is possible to prospectively design an integrated boost to the location of the residual tumor mass. Method and Materials: For 23 easily visualized lesions, tumor volume was measured over the course of treatment using MVCT imaging. The masses of 15 lesions were also measured. Individual response models were created for these lesions using Locally Weighted Regression (LWR). Each model was created using the measured volumetric and mass responses for the remaining lesions. All data related to the lesion being used to test the model were excluded. The model inputs included the measured volume or mass from early in the treatment. Which variables to include, and the combination of observation days was determined using a genetic algorithm (GA) based optimization. Results: The average error between the true and predicted final volumes was 4.5%, while the error for the final mass predictions was 14.6%. The LWR model was accurate in its predictions made at the end treatment. However, the uncertainty in the shape of the tumor response curve increased near the middle of treatment. Conclusion: A novel technique has been developed for predicting lungtumor response. Even with a relatively small patient database, the predicted responses (and their associated uncertainties) at the end of treatment were in agreement with measurement. These results confirm the accuracy that can be achieved by this non‐parametric model when applied to lung data.
34(2007); http://dx.doi.org/10.1118/1.2761348View Description Hide Description
Purpose In radiation therapy,delivereddoses can be accumulated over fractions for adaptive treatment planning. However, the dosereconstruction fidelity can be compromised by image registration errors. The resultant dose discrepancy is hard to measure. This paper proposes a new method to assess the difference between the delivereddose and the warped dose.Method and Materials: The dose warping discrepancy is dominated by deformable image registration errors and source‐dose distributions. Registration errors can be specified within a finite element framework as an unbalanced energy δ R , which is defined at element j by where E 0 and di are Young's modulus and the displacement vector fields of the registration R. E 0Φ j is an assembly of all the element forces relating to the node i. Consequently the dose warping discrepancy at voxel k can be defined as the convolution of the dose divergence Div(D) and δ R : . The effectiveness of the dose‐discrepancy‐convolution (DDC) defined above is demonstrated through applying it to dose computed on ten prostate‐CT images. An IMRT treatment plan is developed on the planning image. In nine subsequent treatments, images are acquired to calculate the corresponding delivereddoses. Their mean and standard‐deviation in Ci , a target contour automatically expanded from prostate delineated on the time‐of‐treatment imagei, are compared with those of their warped doses measured on the planning target volume. The differences in their means and standard‐deviations are denoted by E ε and E σ, respectively.
Results δ R , ε D,R , E ε and E σ are computed for the nine treatment fractions. Fraction one and eight have the largest warping discrepancies identified in all the four evaluation criterions. Conclusion Defined in terms of the deformable registration error, the voxel‐based DDC can be employed for the automatic evaluation of dosereconstruction in the whole dosing domain. Its measurement is consistent to the contour‐based dose warping evaluation performed in the planning target volume.