The reconstructed 3D heart volumes using the advanced NC adaptation process match well with the volumes obtained from CT. The Dice results demonstrate that the heart volume can be reconstructed with an accuracy of about 90%, which is comparable to the volumetric and/or positional variation due to respiration (p = 0.62). Statistically, it has been shown that the NCs made a significant improvement to the population deformation models (p = 0.01).
In this study, 3D heart volumes were reconstructed without lateral depth information. Although a "similar" Reference patient was identified (by thorax measurements) to approximate the lateral depth of the Test patient's heart, there remains an observable discrepancy in the anterior-posterior direction of the reconstructed models. This difference is largely due to the limitation that only anterior-posterior simulator films are available from historical 2D treatment plans. This limitation could introduce error in the computation of heart doses, as variations in heart-tissue density may cause the primary photons to become more or less attenuated than expected. However, current study results also indicated that this reconstruction error is no greater than the uncertainty imposed by a patient's free-breathing motion. Additionally, variation in day-to-day patient positioning will affect dose actually delivered to the heart during treatment [25, 26]. A previous study on the reproducibility of treatment setup for mantle irradiation in HL patients, using sequential port films, found that 29% of the films had minor deviations from original simulation film and 5% were considered unacceptable . Errors were noted in the superior and inferior mediastinum and could only be eliminated by resimulation . Taken together, we believe that the inaccuracies of the reconstruction technique described here are no greater than that caused by organ motion due to free-breathing and other setup uncertainties that are part of clinical practice.
The current NC adaptation technique is entirely based on soft-tissue alignment to allow for complete heart deformation. The manual contours of the heart were included on the DRR to facilitate NC placement. For retrospective studies, the same contours can be used for defining the heart on the Reference DRR. On digitized 2D fluoroscopic films of retrospective patients, the heart shape could also be highlighted as the soft tissue heart contour would in fact be better enhanced by the use of lower kVp at the time of conventional simulation. To further enhance tissue contrast on a 2D simulation film, a high-resolution diagnostic film scanner, combined with film processing software with an adjustable grayscale feature could be used. While it is recognized that overlapping boundaries (heart & ribs) may sometimes be difficult to define on radiographic films, the NC technique overcome this limitation by utilizing only sections of the organ edge in the adaption process. This is one of the major advantages of the NC technique over common segmentation techniques, which require complete organ boundary definition [27, 28]. Specifically, six NCs were applied only to sections of the edges that would most significantly change the shape of the heart (superiorly, inferiorly, & circumflexes of the four chambers) and the entire heart volume was quickly regenerated using the adaptation process.
Another key advantage of the advanced NC technique is its ability to delineate organ shape curvatures using a combination of linear and bilinear adaptation. This technique incorporates a bilinear method to allow multiple NCs to detect shape differences along the same organ edge. Potentially, cubic or bicubic interpolation methods could be used with multiple NCs to further improve reconstruction accuracy [21, 29]. However, the number of NCs employed should be organ-dependent, and calculation times should be balanced with accuracy outcomes. For example, heart volume overlap was computed using two additional NCs in the superior and inferior direction. The additional NCs did not result in a significant increase in volumetric accuracy.
The capacity to recreate 3D organ volumes from 2D planning data potentially allows for better correlation between organ dose and late onset toxicity. Investigation is underway to 1) reconstruct the 3D CT volumes (lungs & heart) and treatment plans of current patients for dosimetric validation of the current adaptation technique, and 2) reproduce the 3D dosimetry of retrospective 2D treatment plans in order to assess and refine existing dose, volume, and outcome relationships [4–7]. The latter process involves combining the use of the traditional film digitizer (ADAC Numonics-Accugrid Digitizer) with the 3D CT-based treatment planning system in order to incorporate shielding (lungs, heart, larynx, C-spine, humeral heads) from a 2D radiograph onto the adapted CT image.
The current development is a preliminary study, limited to the reconstruction of the overall heart volume. While this technique can offer a general dose-volume relationship of the heart, there remains several constraints when combined with 3D dosimetry data. First, localized radiation effects of specific cardiac structures remain unknown. Existing models tend to discard organ-specific spatial information, assuming all regions of the heart are of equal radiosensitivity [4–7]. However, this assumption is inaccurate, as the heart can be defined both anatomically (cardiac chambers, pericardium) and physiologically (cardiac cycles) [7, 30]. Second, the long term cardiac effects of radiation may be confounded with other treatment factors that may require further investigation. For instance, adjuvant chemotherapy is increasingly common for treatment of HL. Patients treated with chemotherapy (anthracyclines) alone were found to have increased cardiac toxicity [31, 32]. In contrast, non-chemo lipid-lowering treatments (statin) have demonstrated risk reduction in cardiac death [33, 34]. Therefore, in order to provide more accurate representation of the organ, future studies could aim at localization of the sub-regions of the heart, modeling the interaction of these sub-regions, and investigation of the combined late effects of radiation and other treatment regimens.