An evaluation of the use of DirectSPR images for proton planning in the RayStation treatment planning software.

An important source of uncertainty in proton therapy treatment planning is the assignment of stopping-power ratio (SPR) from CT data. A commercial product is now available that creates an SPR map directly from dual-energy CT (DECT). This paper investigates the use of this new product in proton treatment planning and compares the results to the current method of assigning SPR based on a single-energy CT (SECT). Two tissue surrogate phantoms were CT scanned using both techniques. The SPRs derived from single-energy CT and by DirectSPR™ were compared to measured values. SECT-based values agreed with measurements within 4% except for low density lung and high density bone, which differed by 13% and 8%, respectively. DirectSPR™ values were within 2% of measured values for all tissues studied. Both methods were also applied to scanned containers of three types of animal tissue, and the expected range of protons of two different energies was calculated in the treatment planning system and compared to the range measured using a multi-layer ion chamber. The average difference between range measurements and calculations based on SPR maps from dual- and single-energy CT, respectively, was 0.1 mm (0.07%) versus 2.2 mm (1.5%). Finally, a phantom was created using a layer of various tissue surrogate plugs on top of a 2D ion chamber array. Dose measurements on this array were compared to predictions using both single- and dual-energy CTs and SPR maps. While standard gamma pass rates for predictions based on DECT-derived SPR maps were slightly higher than those based on single-energy CT, the differences were generally modest for this measurement setup. This study showed that SPR maps created by the commercial product from dual-energy CT can successfully be used in RayStation to generate proton dose distributions and that these predictions agree well with measurements.

Effect of microdistribution of alpha and beta-emitters in targeted radionuclide therapies on delivered absorbed dose in a GATE model of bone marrow.

Acute hematologic toxicity is a frequent adverse effect of beta-emitter targeted radionuclide therapies (TRTs). Alpha emitters have the potential of delivering high linear energy transfer (LET) radiation to the tumor attributed to its shorter range. Antibody-based TRTs have increased blood-pool half-lives, and therefore increased marrow toxicity, which is a particular concern with alpha emitters. Accurate 3D absorbed dose calculations focusing on the interface region of blood vessels and bone can elucidate energy deposition patterns. Firstly, a cylindrical geometry model with a central blood vessel embedded in the trabecular tissue was modeled. Monte Carlo simulations in GATE were performed considering beta (177Lu, 90Y) and alpha emitters (211At, 225Ac) as sources restricted to the blood pool. Subsequently, the radioactive sources were added in the trabecular bone compartment in order to model bone marrow metastases infiltration (BMMI). Radial profiles, dose-volume histograms and voxel relative differences were used to evaluate the absorbed dose results. We demonstrated that alpha emitters have a higher localized energy deposition compared to beta emitters. In the cylindrical geometry model, when the sources are confined to the blood pool, the dose to the trabecular bone is greater for beta emitting radionuclides, as alpha emitters deposit the majority of their energy within 70 µm of the vessel wall. In the BMMI model, alpha emitters have a lower dose to untargeted trabecular bone. Our results suggest that when alpha emitters are restricted to the blood pool, as when labeled to antibodies, hematologic toxicities may be lower than expected due to differences in the microdistribution of delivered absorbed dose.

Dosimetry for Radiopharmaceutical Therapy: Current Practices and Commercial Resources.

With the ongoing dramatic growth of radiopharmaceutical therapy, research and development in internal radiation dosimetry continue to advance both at academic medical centers and in industry. The basic paradigm for patient-specific dosimetry includes administration of a pretreatment tracer activity of the therapeutic radiopharmaceutical; measurement of its time-dependent biodistribution; definition of the pertinent anatomy; integration of the measured time-activity data to derive source-region time-integrated activities; calculation of the tumor, organ-at-risk, and/or whole-body absorbed doses; and prescription of the therapeutic administered activity. This paper provides an overview of the state of the art of patient-specific dosimetry for radiopharmaceutical therapy, including current methods and commercially available software and other resources.

Tumor Response to Radiopharmaceutical Therapies: The Knowns and the Unknowns.

Radiopharmaceutical therapy (RPT) is defined as the delivery of radioactive atoms to tumor-associated targets. In RPT, imaging is built into the mode of treatment since the radionuclides used in RPT often emit photons or can be imaged using a surrogate. Such imaging may be used to estimate tumor-absorbed dose. We examine and try to elucidate those factors that impact the absorbed dose-versus-response relationship for RPT agents. These include the role of inflammation- or immune-mediated effects, the significance of theranostic imaging, radiobiology, differences in dosimetry methods, pharmacokinetic differences across patients, and the impact of tumor hypoxia on response to RPT.

Harmonization of PET image reconstruction parameters in simultaneous PET/MRI.

OBJECTIVE: Simultaneous PET/MRIs vary in their quantitative PET performance due to inherent differences in the physical systems and differences in the image reconstruction implementation. This variability in quantitative accuracy confounds the ability to meaningfully combine and compare data across scanners. In this work, we define image reconstruction parameters that lead to comparable contrast recovery curves across simultaneous PET/MRI systems. METHOD: The NEMA NU-2 image quality phantom was imaged on one GE Signa and on one Siemens mMR PET/MRI scanner. The phantom was imaged at 9.7:1 contrast with standard spheres (diameter 10, 13, 17, 22, 28, 37 mm) and with custom spheres (diameter: 8.5, 11.5, 15, 25, 32.5, 44 mm) using a standardized methodology. Analysis was performed on a 30 min listmode data acquisition and on 6 realizations of 5 min from the listmode data. Images were reconstructed with the manufacturer provided iterative image reconstruction algorithms with and without point spread function (PSF) modeling. For both scanners, a post-reconstruction Gaussian filter of 3-7 mm in steps of 1 mm was applied. Attenuation correction was provided from a scaled computed tomography (CT) image of the phantom registered to the MR-based attenuation images and verified to align on the non-attenuation corrected PET images. For each of these image reconstruction parameter sets, contrast recovery coefficients (CRCs) were determined for the SUVmean, SUVmax and SUVpeak for each sphere. A hybrid metric combining the root-mean-squared discrepancy (RMSD) and the absolute CRC values was used to simultaneously optimize for best match in CRC between the two scanners while simultaneously weighting toward higher resolution reconstructions. The image reconstruction parameter set was identified as the best candidate reconstruction for each vendor for harmonized PET image reconstruction. RESULTS: The range of clinically relevant image reconstruction parameters demonstrated widely different quantitative performance across cameras. The best match of CRC curves was obtained at the lowest RMSD values with: for CRCmean, 2 iterations-7 mm filter on the GE Signa and 4 iterations-6 mm filter on the Siemens mMR, for CRCmax, 4 iterations-6 mm filter on the GE Signa, 4 iterations-5 mm filter on the Siemens mMR and for CRCpeak, 4 iterations-7 mm filter with PSF on the GE Signa and 4 iterations-7 mm filter on the Siemens mMR. Over all reconstructions, the RMSD between CRCs was 1.8%, 3.6% and 2.9% for CRC mean, max and peak, respectively. The solution of 2 iterations-3 mm on the GE Signa and 4 iterations-3 mm on Siemens mMR, both with PSF, led to simultaneous harmonization and with high CRC and low RMSD for CRC mean, max and peak with RMSD values of 2.8%, 5.8% and 3.2%, respectively. CONCLUSIONS: For two commercially available PET/MRI scanners, user-selectable parameters that control iterative updates, image smoothing and PSF modeling provide a range of contrast recovery curves that allow harmonization in harmonization strategies of optimal match in CRC or high CRC values. This work demonstrates that nearly identical CRC curves can be obtained on different commercially available scanners by selecting appropriate image reconstruction parameters.

Experimental characterization and system simulations of depth of interaction PET detectors using 0.5 mm and 0.7 mm LSO arrays.

Small animal PET scanners may be improved by increasing the sensitivity, improving the spatial resolution and improving the uniformity of the spatial resolution across the field of view. This may be achieved by using PET detectors based on crystal elements that are thin in the axial and transaxial directions and long in the radial direction, and by employing depth of interaction (DOI) encoding to minimize the parallax error. With DOI detectors, the diameter of the ring of the PET scanner may also be decreased. This minimizes the number of detectors required to achieve the same solid angle coverage as a scanner with a larger ring diameter and minimizes errors due to non-collinearity of the annihilation photons. In this study, we characterize prototype PET detectors that are finely pixelated with individual LSO crystal element sizes of 0.5 mm x 0.5 mm x 20 mm and 0.7 mm x 0.7 mm x 20 mm, read out at both ends by position sensitive avalanche photodiodes (PSAPDs). Both a specular reflector and a diffuse reflector were evaluated. The detectors were characterized based on the ability to clearly resolve the individual crystal elements, the DOI resolution and the energy resolution. Our results indicate that a scanner based on any of the four detector designs would offer improved spatial resolution and more uniform spatial resolution compared to present day small animal PET scanners. The greatest improvements to spatial resolution will be achieved when the detectors employing the 0.5 mm x 0.5 mm x 20 mm crystals are used. Monte Carlo simulations were performed to demonstrate that 2 mm DOI resolution is adequate to ensure uniform spatial resolution for a small animal PET scanner geometry using these detectors. The sensitivity of such a scanner was also simulated using Monte Carlo simulations and was shown to be greater than 10% for a four ring scanner with an inner diameter of 6 cm, employing 20 detectors per scanner ring.

The Practicality of ICRU and Considerations for Future ICRU Definitions.

The International Commission on Radiation Units and Measurements (ICRU) volumes are standardized volume definitions used in radiation oncology practice that have evolved over time to account for advancements in technology and radiation planning. The current definitions have strengths but also practical limitations. The main limitation is related to the process of accounting for tumor motion during treatment. As radiotherapeutic techniques become more precise, motion interplay effects and anatomical changes during treatment must be taken into account to ensure accurate and safe delivery of treatment. Adaptive replanning can help to mitigate the effect of these uncertainties and widen the therapeutic ratio by maximizing dose to the tumor and protecting critical normal structures. As adaptive replanning becomes more common, standardization of how adaptive therapy is implemented and reported will become necessary.

Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions.

Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT), through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC), as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning.

Evaluation of 3D fluoroscopic image generation from a single planar treatment image on patient data with a modified XCAT phantom.

Accurate understanding and modeling of respiration-induced uncertainties is essential in image-guided radiotherapy. Explicit modeling of the overall lung motion and interaction among different organs promises to be a useful approach. Recently, preliminary studies on 3D fluoroscopic treatment imaging and tumor localization based on principal component analysis motion models and cost function optimization have shown encouraging results. However, the performance of this technique for varying breathing parameters and under realistic conditions remains unclear and thus warrants further investigation. In this work, we present a systematic evaluation of a 3D fluoroscopic image generation algorithm via two different approaches. In the first approach, the model's accuracy is tested for changing parameters for sinusoidal breathing. These parameters include changing respiratory motion amplitude, period and baseline shift. The effects of setup error, imaging noise and different tumor sizes are also examined. In the second approach, we test the model for anthropomorphic images obtained from a modified XCAT phantom. This set of experiments is important as all the underlying breathing parameters are simultaneously tested, as in realistic clinical conditions. Based on our simulation results for more than 250 s of breathing data for eight different lung patients, the overall tumor localization accuracies of the model in left-right, anterior-posterior and superior-inferior directions are 0.1 ± 0.1, 0.5 ± 0.5 and 0.8 ± 0.8 mm, respectively. 3D tumor centroid localization accuracy is 1.0 ± 0.9 mm.

Quantifying ITV instabilities arising from 4DCT: a simulation study using patient data.

Treatment planning for patients undergoing radiation therapy is often performed based on four-dimensional computed tomography (4DCT) when respiratory motion is present, as in lung cancer patients. 4DCT is used to define the internal target volume (ITV) that, ideally, incorporates all potential locations of the tumour. In this work, we use the locations of gold fiducial markers implanted in lung tumours of eight patients to represent tumour motion. These fiducial locations are used in a simulation of a four-slice CT scanner to generate the ITV for 10, 20 and 30 mm diameter model tumours. To demonstrate instabilities in the ITV definition based on 4DCT, the ITV calculation was repeated for the same patients for consecutive scan start times, staggered by 1 s. The volumetric difference in the ITV and the per cent of time that the ITV contains in the tumour are both evaluated. The ITV from a single patient was found to vary by 46%-127% for a tumour diameter of 10 mm. The ITV did not cover the entirety of the tumour 11%-74% of the time for a 10 mm tumour diameter.

Tapered LSO arrays for small animal PET.

By using detectors with good depth encoding accuracy (∼2 mm), an animal PET scanner can be built with a small ring diameter and thick crystals to simultaneously obtain high spatial resolution and high sensitivity. However, there will be large wedge-shaped gaps between detector modules in such a scanner if traditional cuboid crystal arrays are used in a polygonal arrangement. The gaps can be minimized by using tapered scintillator arrays enabling the sensitivity of the scanner to be further improved. In this work, tapered lutetium oxyorthosilicate (LSO) arrays with different crystal dimensions and different combinations of inter-crystal reflector and crystal surface treatments were manufactured and their performance was evaluated. Arrays were read out from both ends by position-sensitive avalanche photodiodes (PSAPDs). In the optimal configuration, arrays consisting of 0.5 mm LSO elements could be clearly resolved and a depth of interaction resolution of 2.6 mm was obtained for a 20 mm thick array. For this tapered array, the intrinsic spatial is degraded from 0.67 to 0.75 mm compared to a standard cuboidal array with similar dimensions, while the increase in efficiency is 41%. Tapered scintillator arrays offer the prospect of improvements in sensitivity and sampling for small-bore scanners, without large increases in manufacturing complexity.