4D tumor centroid tracking using orthogonal 2D dynamic MRI: implications for radiotherapy planning.

PURPOSE: Current pretreatment, 4D imaging techniques are suboptimal in that they sample breathing motion over a very limited "snapshot" in time. Heretofore, long-duration, 4D motion characterization for radiotherapy planning, margin optimization, and validation have been impractical for safety reasons, requiring invasive markers imaged under x-ray fluoroscopy. To characterize 3D tumor motion and associated variability over durations more consistent with treatments, the authors have developed a practical dynamic MRI (dMRI) technique employing two orthogonal planes acquired in a continuous, interleaved fashion. METHODS: 2D balanced steady-state free precession MRI was acquired continuously over 9-14 min at approximately 4 Hz in three healthy volunteers using a commercial 1.5 T system; alternating orthogonal imaging planes (sagittal, coronal, sagittal, etc.) were employed. The 2D in-plane pixel resolution was 2 × 2 mm(2) with a 5 mm slice profile. Simultaneous with image acquisition, the authors monitored a 1D surrogate respiratory signal using a device available with the MRI system. 2D template matching-based anatomic feature registration, or tracking, was performed independently in each orientation. 4D feature tracking at the raw frame rate was derived using spline interpolation. RESULTS: Tracking vascular features in the lung for two volunteers and pancreatic features in one volunteer, the authors have successfully demonstrated this method. Registration error, defined here as the difference between the sagittal and coronal tracking result in the SI direction, ranged from 0.7 to 1.6 mm (1σ) which was less than the acquired image resolution. Although the healthy volunteers were instructed to relax and breathe normally, significantly variable respiration was observed. To demonstrate potential applications of this technique, the authors subsequently explored the intrafraction stability of hypothetical tumoral internal target volumes and 3D spatial probability distribution functions. The surrogate respiratory information allowed the authors to show how this technique can be used to study correlations between internal and external (surrogate) information over these prolonged durations. However, compared against the gold standard of the time stamps in the dMRI frames, the temporal synchronization of the surrogate 1D respiratory information was shown to be likely unreliable. CONCLUSIONS: The authors have established viability of a novel and practical pretreatment, 4D tumor centroid tracking method employing a commercially available dynamic MRI sequence. Further developments from the vendor are likely needed to provide a reliably synchronized surrogate 1D respiratory signal, which will likely broaden the utility of this method in the pretreatment radiotherapy planning context.

Respiration-based sorting of dynamic MRI to derive representative 4D-MRI for radiotherapy planning.

PURPOSE: Current pretreatment, 4D imaging techniques are suboptimal in that they sample breathing motion over a very limited "snap-shot" in time. To potentially address this, the authors have developed a longer-duration MRI and postprocessing technique to derive the average or most-probable state of mobile anatomy and meanwhile capture and convey the observed motion variability. METHODS: Sagittal and coronal multislice, 2D dynamic MRI was acquired in a sequential fashion over extended durations in two abdominal and four lung studies involving healthy volunteers. Two sequences, readily available on a commercial system, were employed. Respiratory interval-correlated, or 4D-MRI, volumes were retrospectively derived using a two-pass approach. In a first pass, a respiratory trace acquired simultaneous with imaging was processed and slice stacking was used to derive a set of MRI volumes, each representing an equal time or proportion of respiration. Herein, all raw 2D frames mapping to the given respiratory interval, per slice location, were averaged. In a second-pass, this prior reconstruction provided a set of template images and a similarity metric was employed to discern the subset of best-matching raw 2D frames for secondary averaging (per slice location and respiratory interval). Breathing variability (per respiratory interval and slice location) was depicted by computing both a maximum intensity projection as well as a pixelwise standard deviation image. RESULTS: These methods were successfully demonstrated in both the lung and abdomen for both applicable sequences, performing reconstructions with ten respiratory intervals. The first-pass (average) resulted in motion-induced blurring, especially for irregular breathing. The authors have demonstrated qualitatively that the second-pass result can mitigate this blurring. CONCLUSIONS: They have presented a novel methodology employing dMRI to derive representative 4D-MRI. This set of techniques are practical in that (1) they employ MRI sequences that are standard across commercial vendors; (2) the 2D imaging planes can be oriented onto an arbitrary axis (e.g., sagittal, coronal, axial[ellipsis (horizontal)]); (3) the image processing techniques are relatively simple. Systematically applying this and similar dMRI-based techniques in patients is a crucial next step to demonstrate efficacy beyond CT-only based practice.

Comparative analysis of traditional and coiled fiducials implanted during EUS for pancreatic cancer patients receiving stereotactic body radiation therapy.

BACKGROUND: EUS-guided fiducial placement facilitates image-guided radiation therapy (IGRT). OBJECTIVE: To compare 2 types of commercially available fiducials for technical success, complications, visibility, and migration. DESIGN: Retrospective, single-center, comparative study. SETTING: Tertiary-care medical center. INTERVENTIONS: Traditional fiducials (TFs) (5-mm length, 0.8-mm diameter) and Visicoil fiducials (VFs) (10-mm length, 0.35-mm diameter) were compared. Fiducials were placed using linear 19-gauge (for TFs) or 22-gauge (for VFs) needles. A subjective visualization scoring system (0-2; 0 = not visible, 1 = barely visible, 2 = clearly visible) was used to assess visibility on CT. Fiducial migration was calculated as a change in interfiducial distance. MAIN OUTCOME MEASUREMENTS: Technical success, complications, visibility, and migration of 2 types of fiducials. RESULTS: Thirty-nine patients with locally advanced pancreatic cancer underwent EUS-guided placement of 103 fiducials (77 TFs, 26 VFs). The mean number of fiducials placed per patient was 2.66 (standard deviation 0.67) for the 19-gauge needle and 2.60 (standard deviation 0.70) for the 22-gauge needle (P = .83). No intra- or postprocedural complications were encountered. The median visibility score for TFs was significantly better than that for VFs, both when scores of 0 were and were not included (2.00, interquartile range [IQR] 2.00-2.00 vs 1.75, IQR 1.50-2.00, P = .009 and 2.00, IQR 2.00-2.00 vs 2.00, IQR 1.50-2.00, P < .0001, respectively). The mean migration was not significantly different between the 2 types of fiducials (0.8 mm [IQR 0.4-1.6 mm] for TFs vs 1.3 mm [IQR 0.6-1.5 mm] for VFs; P = .72). LIMITATIONS: Retrospective, nonrandomized design. CONCLUSIONS: Visibility was significantly better for TFs compared with VFs. The degree of fiducial migration was not significantly different for TFs and VFs. There was no significant difference in the mean number of fiducials placed, indicating a similar degree of technical difficulty for TF and VF deployment.

The radiobiological P(+) index for pretreatment plan assessment with emphasis on four-dimensional radiotherapy modalities.

PURPOSE: Radiation treatment modalities will continue to emerge that promise better clinical outcomes albeit technologically challenging to implement. An important question facing the radiotherapy community then is the need to justify the added technological effort for the clinical return. Mobile tumor radiotherapy is a typical example, where 4D tumor tracking radiotherapy (4DTRT) has been proposed over the simpler conventional modality for better results. The modality choice per patient can depend on a wide variety of factors. In this work, we studied the complication-free tumor control probability (P(+)) index, which combines the physical complexity of the treatment plan with the radiobiological characteristics of the clinical case at hand and therefore found to be useful in evaluating different treatment techniques and estimating the expected clinical effectiveness of different radiation modalities. METHODS: 4DCT volumes of 18 previously treated lung cancer patients with tumor motion and size ranging from 2 mm to 15 mm and from 4 cc to 462 cc, respectively, were used. For each patient, 4D treatment plans were generated to extract the 4D dose distributions, which were subsequently used with clinically derived radiobiological parameters to compute the P(+) index per modality. RESULTS: The authors observed, on average, a statistically significant increase in P(+) of 3.4% ± 3.8% (p < 0.003) in favor of 4DTRT. There was high variability among the patients with a <0.5% up to 13.4% improvement in P(+). CONCLUSIONS: The observed variability in the improvement of the clinical effectiveness suggests that the relative benefit of tracking should be evaluated on a per patient basis. Most importantly, this variability could be effectively captured in the computed P(+). The index can thus be useful to discriminate and hence point out the need for a complex modality like 4DTRT over another. Besides tumor mobility, a wide range of other factors, e.g., size, location, fractionation, etc., can affect the relative benefits. Application of the P(+) objective is a simple and effective way to combine these factors in the evaluation of a treatment plan.

A method for deriving a 4D-interpolated balanced planning target for mobile tumor radiotherapy.

PURPOSE: Tumor control and normal tissue toxicity are strongly correlated to the tumor and normal tissue volumes receiving high prescribed dose levels in the course of radiotherapy. Planning target definition is, therefore, crucial to ensure favorable clinical outcomes. This is especially important for stereotactic body radiation therapy of lung cancers, characterized by high fractional doses and steep dose gradients. The shift in recent years from population-based to patient-specific treatment margins, as facilitated by the emergence of 4D medical imaging capabilities, is a major improvement. The commonly used motion-encompassing, or internal-target volume (ITV), target definition approach provides a high likelihood of coverage for the mobile tumor but inevitably exposes healthy tissue to high prescribed dose levels. The goal of this work was to generate an interpolated balanced planning target that takes into account both tumor coverage and normal tissue sparing from high prescribed dose levels, thereby improving on the ITV approach. METHODS: For each 4DCT dataset, 4D deformable image registration was used to derive two bounding targets, namely, a 4D-intersection and a 4D-composite target which minimized normal tissue exposure to high prescribed dose levels and maximized tumor coverage, respectively. Through definition of an "effective overlap volume histogram" the authors derived an "interpolated balanced planning target" intended to balance normal tissue sparing from prescribed doses with tumor coverage. To demonstrate the dosimetric efficacy of the interpolated balanced planning target, the authors performed 4D treatment planning based on deformable image registration of 4D-CT data for five previously treated lung cancer patients. Two 4D plans were generated per patient, one based on the interpolated balanced planning target and the other based on the conventional ITV target. Plans were compared for tumor coverage and the degree of normal tissue sparing resulting from the new approach was quantified. RESULTS: Analysis of the 4D dose distributions from all five patients showed that while achieving tumor coverage comparable to the ITV approach, the new planning target definition resulted in reductions of lung V(10), V(20), and V(30) of 6.3% ± 1.7%, 10.6% ± 3.9%, and 12.9% ± 5.5%, respectively, as well as reductions in mean lung dose, mean dose to the GTV-ring and mean heart dose of 8.8% ± 2.5%, 7.2% ± 2.5%, and 10.6% ± 3.6%, respectively. CONCLUSIONS: The authors have developed a simple and systematic approach to generate a 4D-interpolated balanced planning target volume that implicitly incorporates the dynamics of respiratory-organ motion without requiring 4D-dose computation or optimization. Preliminary results based on 4D-CT data of five previously treated lung patients showed that this new planning target approach may improve normal tissue sparing without sacrificing tumor coverage.

Incorporating system latency associated with real-time target tracking radiotherapy in the dose prediction step.

System latency introduces geometric errors in the course of real-time target tracking radiotherapy. This effect can be minimized, for example by the use of predictive filters, but cannot be completely avoided. In this work, we present a convolution technique that can incorporate the effect as part of the treatment planning process. The method can be applied independently or in conjunction with the predictive filters to compensate for residual latency effects. The implementation was performed on TrackBeam (Initia Ltd, Israel), a prototype real-time target tracking system assembled and evaluated at our Cancer Institute. For the experimental system settings examined, a Gaussian distribution attributable to the TrackBeam latency was derived with sigma = 3.7 mm. The TrackBeam latency, expressed as an average response time, was deduced to be 172 ms. Phantom investigations were further performed to verify the convolution technique. In addition, patient studies involving 4DCT volumes of previously treated lung cancer patients were performed to incorporate the latency effect in the dose prediction step. This also enabled us to effectively quantify the dosimetric and radiobiological impact of the TrackBeam and other higher latency effects on the clinical outcome of a real-time target tracking delivery.

A radiobiological analysis of the effect of 3D versus 4D image-based planning in lung cancer radiotherapy.

Dose distributions generated on a static anatomy may differ significantly from those delivered to temporally varying anatomy such as for abdominal and thoracic tumors, due largely in part to the unavoidable organ motion and deformation effects stemming from respiration. In this work, the degree of such variation for three treatment techniques, namely static conventional, gating and target tracking radiotherapy, was investigated. The actual delivered dose was approximated by planning all the phases of a 4DCT image set. Data from six (n = 6) previously treated lung cancer patients were used for this study with tumor motion ranging from 2 to 10 mm. Complete radiobiological analyses were performed to assess the clinical significance of the observed discrepancies between the 3D and 4DCT image-based dose distributions. Using the complication-free tumor control probability (P+) objective, we observed small differences in P+ between the 3D and 4DCT image-based plans (<2.0% difference on average) for the gating and static conventional regimens and higher differences in P+ (4.0% on average) for the tracking regimen. Furthermore, we observed, as a general trend, that the 3D plan underestimated the P+ values. While it is not possible to draw any general conclusions from a small patient cohort, our results suggest that there exists a patient population in which 4D planning does not provide any additional benefits beyond that afforded by 3D planning for static conventional or gated radiotherapy. This statement is consistent with previous studies based on physical dosimetric evaluations only. The higher differences observed with the tracking technique suggest that individual patient plans should be evaluated on a case-by-case basis to assess if 3D or 4D imaging is appropriate for the tracking technique.

A prediction study on radiation-induced second malignancies for IMRT treatment delivery.

Low-level peripheral organ dose and its effect on second malignancies for patients undergoing radiation therapy have been reported in the literature. However, a comprehensive database outlining the treatment modalities, the tumor location, and a quantification of the overall relative risk of second malignancies is rather limited. In this work, we quantify the relative risks or percent likelihood of second malignancies for patients undergoing IMRT and conventional radiotherapy for four different tumor sites: breast, head and neck, lung, and prostate. We utilize Monte Carlo methods based on actual patient plans to compute the whole body effective dose equivalent for each plan and then deduce the percent likelihood of the occurrence of second malignancy. Based on an evaluation of over 30 actual patient plans and Monte Carlo simulations using 6, 10, and 18MV photon beam energies, we observed that the IMRT patients treated for head and neck cancer showed a 40% increase in risk for developing a second malignancy compared to those treated with conventional radiotherapy. The increase in risk for prostrate patients was 30% while the IMRT lung patients gave the highest relative risk almost tripling that observed in their conventionally treated counterparts. There was negligible difference in risk between breast patients undergoing IMRT treatment versus conventional therapy. The overall relative risk of radiation induced malignancy observed was below 6% in all treatment plans considered.

Measurement and comparison of skin dose for prostate and head-and-neck patients treated on various IMRT delivery systems.

Treatment planning systems inaccurately quantify dose deposited to the skin in the course of radiotherapy owing to their inability to properly account for all the surface dose contributing factors. In this work, we describe a technique for accurately measuring skin dose using ultra-thin thermoluminescent dosimeters and EBT gafchromic films. We investigated the variation in average skin dose for prostate and head-and-neck patients undergoing radiotherapy on three IMRT systems including serial/helical tomotherapy, and IMRT-step and shoot system. Helical tomotherapy was observed to deposit the highest average skin dose followed by serial tomotherapy delivery system.