Organ sparing of linac-based targeted marrow irradiation over total body irradiation.

PURPOSE: Targeted marrow irradiation (TMI) is an alternative conditioning regimen to total body irradiation (TBI) before bone marrow transplantation in hematologic malignancies. Intensity-modulation methods of external beam radiation therapy are intended to permit significant organ sparing while maintaining adequate target coverage, improving the therapeutic ratio. This study directly compares the dose distributions to targets and organs at risk from TMI and TBI, both modalities conducted by general-use medical linacs at our institution. METHODS: TMI treatments were planned for 10 patients using multi-isocentric feathered volumetric arc therapy (VMAT) plans, delivered by 6 MV photon beams of Elekta Synergy linacs. The computed tomography (CT) datasets used to obtain these plans were also used to generate dose distributions of TBI treatments given in the AP/PA extended-field method. We compared dose distributions normalized to the same prescription for both plan types. The generalized equivalent uniform dose (gEUD) of Niemierko for organs and target volumes was used to quantify effective whole structure dose and dose savings. RESULTS: For the clinical target volume (CTV), no significant differences were found in mean dose or gEUD, although the radical dose homogeneity index (minimum dose divided by maximum dose) was 31.7% lower (P = 0.002) and the standard deviation of dose was 28.0% greater (P = 0.027) in the TMI plans than in the TBI plans. For the TMI plans, gEUD to the lungs, brain, kidneys, and liver was significantly lower (P < 0.001) by 47.8%, 33.3%, 55.4%, and 51.0%, respectively. CONCLUSION: TMI is capable of maintaining CTV coverage as compared to that achieved in TBI, while significantly sparing organs at risk. Improvement on sparing organs at risk permits a higher prescribed dose to the target or the maximum number of times marrow conditioning may be delivered to a patient while maintaining similar typical tissue complication rates.

Machine learning-based dual-energy CT parametric mapping.

The aim is to develop and evaluate machine learning methods for generating quantitative parametric maps of effective atomic number (Zeff), relative electron density (ρ e), mean excitation energy (I x ), and relative stopping power (RSP) from clinical dual-energy CT data. The maps could be used for material identification and radiation dose calculation. Machine learning methods of historical centroid (HC), random forest (RF), and artificial neural networks (ANN) were used to learn the relationship between dual-energy CT input data and ideal output parametric maps calculated for phantoms from the known compositions of 13 tissue substitutes. After training and model selection steps, the machine learning predictors were used to generate parametric maps from independent phantom and patient input data. Precision and accuracy were evaluated using the ideal maps. This process was repeated for a range of exposure doses, and performance was compared to that of the clinically-used dual-energy, physics-based method which served as the reference. The machine learning methods generated more accurate and precise parametric maps than those obtained using the reference method. Their performance advantage was particularly evident when using data from the lowest exposure, one-fifth of a typical clinical abdomen CT acquisition. The RF method achieved the greatest accuracy. In comparison, the ANN method was only 1% less accurate but had much better computational efficiency than RF, being able to produce parametric maps in 15 s. Machine learning methods outperformed the reference method in terms of accuracy and noise tolerance when generating parametric maps, encouraging further exploration of the techniques. Among the methods we evaluated, ANN is the most suitable for clinical use due to its combination of accuracy, excellent low-noise performance, and computational efficiency.

Generation of brain pseudo-CTs using an undersampled, single-acquisition UTE-mDixon pulse sequence and unsupervised clustering.

PURPOSE: MR-based pseudo-CT has an important role in MR-based radiation therapy planning and PET attenuation correction. The purpose of this study is to establish a clinically feasible approach, including image acquisition, correction, and CT formation, for pseudo-CT generation of the brain using a single-acquisition, undersampled ultrashort echo time (UTE)-mDixon pulse sequence. METHODS: Nine patients were recruited for this study. For each patient, a 190-s, undersampled, single acquisition UTE-mDixon sequence of the brain was acquired (TE = 0.1, 1.5, and 2.8 ms). A novel method of retrospective trajectory correction of the free induction decay (FID) signal was performed based on point-spread functions of three external MR markers. Two-point Dixon images were reconstructed using the first and second echo data (TE = 1.5 and 2.8 ms). R2(∗) images (1/T2(∗)) were then estimated and were used to provide bone information. Three image features, i.e., Dixon-fat, Dixon-water, and R2(∗), were used for unsupervised clustering. Five tissue clusters, i.e., air, brain, fat, fluid, and bone, were estimated using the fuzzy c-means (FCM) algorithm. A two-step, automatic tissue-assignment approach was proposed and designed according to the prior information of the given feature space. Pseudo-CTs were generated by a voxelwise linear combination of the membership functions of the FCM. A low-dose CT was acquired for each patient and was used as the gold standard for comparison. RESULTS: The contrast and sharpness of the FID images were improved after trajectory correction was applied. The mean of the estimated trajectory delay was 0.774 µs (max: 1.350 µs; min: 0.180 µs). The FCM-estimated centroids of different tissue types showed a distinguishable pattern for different tissues, and significant differences were found between the centroid locations of different tissue types. Pseudo-CT can provide additional skull detail and has low bias and absolute error of estimated CT numbers of voxels (-22 ± 29 HU and 130 ± 16 HU) when compared to low-dose CT. CONCLUSIONS: The MR features generated by the proposed acquisition, correction, and processing methods may provide representative clustering information and could thus be used for clinical pseudo-CT generation.

k-space sampling optimization for ultrashort TE imaging of cortical bone: applications in radiation therapy planning and MR-based PET attenuation correction.

PURPOSE: The ultrashort echo-time (UTE) sequence is a promising MR pulse sequence for imaging cortical bone which is otherwise difficult to image using conventional MR sequences and also poses strong attenuation for photons in radiation therapy and PET imaging. The authors report here a systematic characterization of cortical bone signal decay and a scanning time optimization strategy for the UTE sequence through k-space undersampling, which can result in up to a 75% reduction in acquisition time. Using the undersampled UTE imaging sequence, the authors also attempted to quantitatively investigate the MR properties of cortical bone in healthy volunteers, thus demonstrating the feasibility of using such a technique for generating bone-enhanced images which can be used for radiation therapy planning and attenuation correction with PET/MR. METHODS: An angularly undersampled, radially encoded UTE sequence was used for scanning the brains of healthy volunteers. Quantitative MR characterization of tissue properties, including water fraction and R2(∗) = 1/T2(∗), was performed by analyzing the UTE images acquired at multiple echo times. The impact of different sampling rates was evaluated through systematic comparison of the MR image quality, bone-enhanced image quality, image noise, water fraction, and R2(∗) of cortical bone. RESULTS: A reduced angular sampling rate of the UTE trajectory achieves acquisition durations in proportion to the sampling rate and in as short as 25% of the time required for full sampling using a standard Cartesian acquisition, while preserving unique MR contrast within the skull at the cost of a minimal increase in noise level. The R2(∗) of human skull was measured as 0.2-0.3 ms(-1) depending on the specific region, which is more than ten times greater than the R2(∗) of soft tissue. The water fraction in human skull was measured to be 60%-80%, which is significantly less than the >90% water fraction in brain. High-quality, bone-enhanced images can be generated using a reduced sampled UTE sequence with no visible compromise in image quality and they preserved bone-to-air contrast with as low as a 25% sampling rate. CONCLUSIONS: This UTE strategy with angular undersampling preserves the image quality and contrast of cortical bone, while reducing the total scanning time by as much as 75%. The quantitative results of R2(∗) and the water fraction of skull based on Dixon analysis of UTE images acquired at multiple echo times provide guidance for the clinical adoption and further parameter optimization of the UTE sequence when used for radiation therapy and MR-based PET attenuation correction.

The role of imaging in radiation therapy planning: past, present, and future.

The use of ionizing radiation for cancer treatment has undergone extraordinary development during the past hundred years. The advancement of medical imaging has been critical in helping to achieve this change. The invention of computed tomography (CT) was pivotal in the development of treatment planning. Despite some disadvantages, CT remains the only three-dimensional imaging modality used for dose calculation. Newer image modalities, such as magnetic resonance (MR) imaging and positron emission tomography (PET), are also used secondarily in the treatment-planning process. MR, with its better tissue contrast and resolution than those of CT, improves tumor definition compared with CT planning alone. PET also provides metabolic information to supplement the CT and MR anatomical information. With emerging molecular imaging techniques, the ability to visualize and characterize tumors with regard to their metabolic profile, active pathways, and genetic markers, both across different tumors and within individual, heterogeneous tumors, will inform clinicians regarding the treatment options most likely to benefit a patient and to detect at the earliest time possible if and where a chosen therapy is working. In the post-human-genome era, multimodality scanners such as PET/CT and PET/MR will provide optimal tumor targeting information.

Determination of planning target volume for whole stomach irradiation using daily megavoltage computed tomographic images.

PURPOSE: Whole stomach radiation therapy is often used in the management of gastric lymphoma. However, very limited data exist with regard to planning target volume requirements for the whole stomach. This study retrospectively analyzed daily megavoltage computed tomographic (CT) scans of gastric lymphoma patients in order to help determine the interfraction variation of the stomach position. METHODS AND MATERIALS: Forty-one daily megavoltage CT images from 3 gastric lymphoma patients were used for stomach contouring. Each patient's megavoltage CT images were rigidly registered to their CT simulation data sets, and the margin in each direction that covered at least 95% of the daily stomach volumes was computed using a simple grid search. Patient setup variation was also calculated from the daily patient shifts. The organ motion margin was then added to the setup margin to render the total margin. RESULTS: A uniform margin of 2.2 cm is required to cover 95% of the stomach over the treatment course. However, direction-specific margins were observed from 1.72, 1.88, 0.92, 2.23, 1.90, and 0.86 cm for the right, left, posterior, anterior, superior, and inferior directions, respectively. CONCLUSIONS: The results of this study provide helpful 3-dimensional volumetric information to the limited existing data on margin requirements for whole stomach radiation therapy.

A prospective study of differences in duodenum compared to remaining small bowel motion between radiation treatments: implications for radiation dose escalation in carcinoma of the pancreas.

PURPOSE: As a foundation for a dose escalation trial, we sought to characterize duodenal and non-duodenal small bowel organ motion between fractions of pancreatic radiation therapy. PATIENTS AND METHODS: Nine patients (4 women, 5 men) undergoing radiation therapy were enrolled in this prospective study. The patients had up to four weekly CT scans performed during their course of radiation therapy. Pancreas, duodenum and non-duodenal small bowel were then contoured for each CT scan. On the initial scan, a four-field plan was generated to fully cover the pancreas. This plan was registered to each subsequent CT scan. Dose-volume histogram (DVH) analyses were performed for the duodenum, non-duodenal small bowel, large bowel, and pancreas. RESULTS: With significant individual variation, the volume of duodenum receiving at least 80% of the prescribed dose was consistently greater than the remaining small bowel. In the patient with the largest inter-fraction variation, the fractional volume of non-duodenal small bowel irradiated to at least the 80% isodose line ranged from 1% to 20%. In the patient with the largest inter-fraction variation, the fractional volume of duodenum irradiated to at least the 80% isodose line ranged from 30% to 100%. CONCLUSION: The volume of small bowel irradiated during four-field pancreatic radiation therapy changes substantially between fractions. This suggests dose escalation may be possible. However, dose limits to the duodenum should be stricter than for other segments of small bowel.