Design of a novel 5-camera surface guidance system with multiple imaging isocenters.

PURPOSE/OBJECTIVE(S): Surface-guided radiation therapy (SGRT) can track the patient surface noninvasively to complement radiographic image-guided radiation therapy with a standard 3-camera system and a single radiation/image isocenter. Here we report the commissioning of a novel SGRT system that monitors three imaging isocenters locations in a proton half-gantry room with a unique 5-camera configuration. MATERIALS/METHODS: The proton half-gantry room has three image isocenters, designated ISO-0, ISO-1, and ISO-2, to cover various anatomical sites via a robotic ceiling-mounted cone-beam CT. Although ISO-0 and ISO-1 are used to image the cranium, head and neck, and thoracic regions, ISO-2 is often used to image body and extremity sites and contiguous craniospinal target volumes. The five-camera system was calibrated to the radiographic isocenter by using a stereotactic radiosurgery cube phantom for each image isocenter. RESULTS: The performance of this 5-camera system was evaluated for 6 degrees of freedom in three categories: (1) absolute setup accuracy relative to the radiographic kV image isocenter based on the DICOM reference; (2) relative shift accuracy based on a reference surface capture; and (3) isocenter tracking accuracy from one isocenter to another based on a reference surface capture. The evaluation revealed maximum deviations of 0.8, 0.2, and 0.6 mm in translation and 0.2°, 0.1°, and 0.1° in rotation for the first, second, and third categories, respectively. Comparing the dosimetry and latency with static and gated irradiation revealed a 0.1% dose difference and positional differences of 0.8 mm in X and 0.9 mm in Y with less than 50 ms temporal accuracy. CONCLUSION: The unique 5-camera system configuration provides SGRT at the treatment isocenter (ISO-0) and also imaging isocenter locations (ISO-0, ISO-1, and ISO-2) to ensure correct patient positioning before and after radiographic imaging, especially during transitions from the offset imaging isocenters to the treatment isocenter.

A comparison of the dosimetric effects of intrafraction motion on step-and-shoot, compensator, and helical tomotherapy-based IMRT.

Intrafraction motion during intensity-modulated radiation therapy can cause differences between the planned and delivered patient dose. The magnitude of these differences is dependent on a number of variables, including the treatment modality. This study was designed to compare the relative susceptibility of plans generated with three different treatment modalities to intrafraction motion. The dosimetric effects of motion were calculated using computational algorithms for seven lung tumor patients. Three delivery techniques - MLC-based step-and-shoot (SNS), beam attenuating compensators, and helical tomotherapy (HT) - were investigated. In total 840 motion-encoded dose-volume histograms (DVHs) were calculated for various combinations of CTV margins and sinusoidal CTV motion including CTV offsets. DVH-based metrics (e.g., D95% and D05%) were used to score plan degradations. For all three modalities, dosimetric degradations were typically smaller than 3% if the CTV displacement was smaller than the CTV margin. For larger displacements, technique and direction-specific sensitivities existed. While the HT plans show similar D95% degradations for motion in the SI and AP directions, SNS and compensator plans showed larger D95% degradations for motion in the SI direction than for motion in the AP direction. When averaged over all motion/margin combinations, compensator plans resulted in 0.9% and 0.6% smaller D95% reductions compared to SNS and HT plans, respectively. These differences were statistically significant. No statistically significant differences in D95% degradations were found between SNS and HT for data averaged over all margin and motion track combinations. For CTV motion that is larger than the CTV margin, the dosimetric impact on the CTV varies with treatment technique and the motion direction. For the cases presented here, the effect of motion on CTV dosimetry was statistically smaller for compensator deliveries than SNS and HT, likely due to the absence of the interplay effect which is present for the more dynamic treatment deliveries. The differences between modalities were, however, small and might not be clinically significant. As expected, margins that envelop the CTV motion provide dosimetric protection against motion for all three modalities.

Analyzing the impact of intrafraction motion: correlation of different dose metrics with changes in target D95%.

PURPOSE: A number of techniques are available to determine the dosimetric impact of intrafraction motion during intensity modulated radiation therapy (IMRT). Motion-induced dose perturbations can be determined both computationally and experimentally using a number of different dosimetric metrics. However, these measures may lead to different conclusions regarding the clinical impact of motion. This study compares the analysis of identical dose perturbations using different dosimetric metrics. Calculated changes in target D95% are used as a reference. METHODS: A total of 3768 motion-encoded dose distributions were calculated for nine lung tumor patients. The motion-encoded dose distributions were compared to static dose distributions using three dosimetric metrics: 2D gamma, 3D gamma, and histogram analysis. Each of these metrics was used to analyze dose perturbations both globally and within the target structure. Furthermore, the failing voxels were analyzed separately according to failure mode, i.e., under vs. over-dosed voxels. Metrics were evaluated based on their agreement with changes in target D95%. Evaluations included the metrics' maximum average sensitivity and specificity (MASS) in detecting unacceptable deliveries, a coefficient correlated to ranking (tau), and the linear correlation coefficient, r. RESULTS: Of the evaluated metrics, the histogram metric restricted to the under-dosed voxels within the target agreed best with changes in target D95%. This metric achieved a MASS of 0.93, a tau of 0.69, and an r-value of 0.85. In comparison, the unrestricted 2D gamma metric achieved MASS = 0.77, tau = 0.40, and r = 0.67. Restricting the 2D gamma test both geographically and in failure mode increased the MASS to 0.85, tau to 0.70, and the r-value to 0.80. CONCLUSIONS: This study suggests that any clinical decisions based solely on an unrestricted 2D gamma metric are suboptimal. A geographic and failure mode restriction can improve results. The remaining uncertainties with non-DVH (dose volume histogram) based metrics should be kept in mind when they are used to evaluate the dosimetric impact of target motion.

A computational method for estimating the dosimetric effect of intra-fraction motion on step-and-shoot IMRT and compensator plans.

Intra-fraction organ motion during intensity-modulated radiation therapy (IMRT) treatment can cause differences between the planned and the delivered dose distribution. To investigate the extent of these dosimetric changes, a computational model was developed and validated. The computational method allows for calculation of the rigid motion perturbed three-dimensional dose distribution in the CT volume and therefore a dose volume histogram-based assessment of the dosimetric impact of intra-fraction motion on a rigidly moving body. The method was developed and validated for both step-and-shoot IMRT and solid compensator IMRT treatment plans. For each segment (or beam), fluence maps were exported from the treatment planning system. Fluence maps were shifted according to the target position deduced from a motion track. These shifted, motion-encoded fluence maps were then re-imported into the treatment planning system and were used to calculate the motion-encoded dose distribution. To validate the accuracy of the motion-encoded dose distribution the treatment plan was delivered to a moving cylindrical phantom using a programmed four-dimensional motion phantom. Extended dose response (EDR-2) film was used to measure a planar dose distribution for comparison with the calculated motion-encoded distribution using a gamma index analysis (3% dose difference, 3 mm distance-to-agreement). A series of motion tracks incorporating both inter-beam step-function shifts and continuous sinusoidal motion were tested. The method was shown to accurately predict the film's dose distribution for all of the tested motion tracks, both for the step-and-shoot IMRT and compensator plans. The average gamma analysis pass rate for the measured dose distribution with respect to the calculated motion-encoded distribution was 98.3 +/- 0.7%. For static delivery the average film-to-calculation pass rate was 98.7 +/- 0.2%. In summary, a computational technique has been developed to calculate the dosimetric effect of intra-fraction motion. This technique has the potential to evaluate a given plan's sensitivity to anticipated organ motion. With knowledge of the organ's motion it can also be used as a tool to assess the impact of measured intra-fraction motion after dose delivery.

Assessing manganese efflux using SEA0400 and cardiac T1-mapping manganese-enhanced MRI in a murine model.

The sodium-calcium exchanger (NCX) is one of the transporters contributing to the control of intracellular calcium (Ca(2+)) concentration by normally mediating net Ca(2+) efflux. However, the reverse mode of the NCX can cause intracellular Ca(2+) concentration overload, which exacerbates the myocardial tissue injury resulting from ischemia. Although the NCX inhibitor SEA0400 has been shown to therapeutically reduce myocardial injury, no in vivo technique exists to monitor intracellular Ca(2+) fluctuations produced by this drug. Cardiac manganese-enhanced MRI (MEMRI) may indirectly assess Ca(2+) efflux by estimating changes in manganese (Mn(2+)) content in vivo, since Mn(2+) has been suggested as a surrogate marker for Ca(2+). This study used the MEMRI technique to examine the temporal features of cardiac Mn(2+) efflux by implementing a T(1)-mapping method and inhibiting the NCX with SEA0400. The change in (1)H(2)O longitudinal relaxation rate, Delta R(1), in the left ventricular free wall, was calculated at different time points following infusion of 190 nmol/g manganese chloride (MnCl(2)) in healthy adult male mice. The results showed 50% MEMRI signal attenuation at 3.4 +/- 0.6 h post-MnCl(2) infusion without drug intervention. Furthermore, treatment with 50 +/- 0.2 mg/kg of SEA0400 significantly reduced the rate of decrease in Delta R(1). At 4.9-5.9 h post-MnCl(2) infusion, the average Delta R(1) values for the two groups treated with SEA0400 were 2.46 +/- 0.29 and 1.72 +/- 0.24 s(-1) for 50 and 20 mg/kg doses, respectively, as compared to the value of 1.27 +/- 0.28 s(-1) for the control group. When this in vivo data were compared to ex vivo absolute manganese content data, the MEMRI T(1)-mapping technique was shown to effectively quantify Mn(2+) efflux rates in the myocardium. Therefore, combining an NCX inhibitor with MEMRI may be a useful technique for assessing Mn(2+) transport mechanisms and rates in vivo, which may reflect changes in Ca(2+) transport.

Monitoring dynamic alterations in calcium homeostasis by T (1)-weighted and T (1)-mapping cardiac manganese-enhanced MRI in a murine myocardial infarction model.

Manganese has been used as a T(1)-weighted MRI contrast agent in a variety of applications. Because manganese ions (Mn(2+)) enter viable myocardial cells via voltage-gated Ca(2+) channels, manganese-enhanced MRI is sensitive to the viability and inotropic state of the heart. In spite of the established importance of Ca(2+) regulation in the heart both before and after myocardial injury, monitoring strategies to assess Ca(2+) homeostasis in affected cardiac tissues are limited. This study implements a T(1)-mapping method to obtain quantitative information both dynamically and over a range of MnCl(2) infusion doses. To optimize the current Mn(2+) infusion protocols, we performed both dose-dependent and temporal washout studies. A non-linear relationship between infused MnCl(2) solution dose and increase in left ventricular wall relaxation rate (DeltaR(1)) was observed. Control mice also exhibited significant Mn(2+) clearance over time, with a decrease in DeltaR(1) of approximately 50% occurring in just 2.5 h. The complicated efflux time dependence possibly suggests multiple efflux mechanisms. With the use of the measured relationship between infused Mn(2+) dose, DeltaR(1), and inductively coupled plasma mass spectrometry data analysis provided a means of estimating the absolute heart Mn concentration in vivo. We show that this technique has the sensitivity to observe or monitor potential alterations in Ca(2+) handling in vivo because of the physiological remodeling after myocardial infarction. Left ventricular free wall DeltaR(1) values were significantly lower (P = 0.005) in the adjacent zone, surrounding the injured myocardial tissue, than in healthy tissue. This inferred reduction in Mn concentration can be used to estimate potentially salvageable myocardium in vivo for future treatment or evaluation of disease progression.