Yulin Song

Advances in 4D Medical Imaging and 4D Radiation Therapy

This paper reviews recent advances in 4D medical imaging (4DMI) and 4D radiation therapy (4DRT), which study, characterize, and minimize patient motion during the processes of imaging and radiotherapy. Patient motion is inevitably present in these processes, producing artifacts and uncertainties in target (lesion) identification, delineation, and localization. 4DMI includes time-resolved volumetric CT, MRI, PET, PET/CT, SPECT, and US imaging. To enhance the performance of these volumetric imaging techniques, parallel multi-detector array has been employed for acquiring image projections and the volumetric image reconstruction has been advanced from the 2D to the 3D tomography paradigm. The time information required for motion characterization in 4D imaging can be obtained either prospectively or retrospectively using respiratory gating or motion tracking techniques. The former acquires snapshot projections for reconstructing a motion-free image. The latter acquires image projections continuously with an associated timestamp indicating respiratory phases using external surrogates and sorts these projections into bins that represent different respiratory phases prior to reconstructing the cyclical series of 3D images. These methodologies generally work for all imaging modalities with variations in detailed implementation. In 4D CT imaging, both multi-slice CT (MSCT) and cone-beam CT (CBCT) are applicable in 4D imaging. In 4D MR imaging, parallel imaging with multi-coil-detectors has made 4D volumetric MRI possible. In 4D PET and SPECT, rigid and non-rigid motions can be corrected with aid of rigid and deformable registration, respectively, without suffering from low statistics due to signal binning. In 4D PET/CT and SPECT/CT, a single set of 4D images can be utilized for motion-free image creation, intrinsic registration, and attenuation correction. In 4D US, volumetric ultrasonography can be employed to monitor fetal heart beating with relatively high temporal resolution. 4DRT aims to track and compensate for target motion during radiation treatment, minimizing normal tissue injury, especially critical structures adjacent to the target, and/or maximizing radiation dose to the target. 4DRT requires 4DMI, 4D radiation treatment planning (4D RTP), and 4D radiation treatment delivery (4D RTD). Many concepts in 4DRT are borrowed, adapted and extended from existing image-guided radiation therapy (IGRT) and adaptive radiation therapy (ART). The advantage of 4DRT is its promise of sparing additional normal tissue by synchronizing the radiation beam with the moving target in real-time. 4DRT can be implemented differently depending upon how the time information is incorporated and utilized. In an ideal situation, the motion adaptive approach guided by 4D imaging should be applied to both RTP and RTD. However, until new automatic planning and motion feedback tools are developed for 4DRT, clinical implementation of ideal 4DRT will meet with limited success. However, simplified forms of 4DRT have been implemented with minor modifications of existing planning and delivery systems. The most common approach is the use of gating techniques in both imaging and treatment, so that the planned and treated target localizations are identical. In 4D planning, the use of a single planning CT image, which is representative of the statistical respiratory mean, seems preferable. In 4D delivery, on-site CBCT imaging or 3D US localization imaging for patient setup and internal fiducial markersfor target motion tracking can significantly reduce the uncertainty in treatment delivery, providing improved normal tissue sparing. Most of the work on 4DRT can be regarded as a proof-of-principle and 4DRT is still in its early stage of development.

Three independent one-dimensional margins for single-fraction frameless stereotactic radiosurgery brain cases using CBCT.

PURPOSEnSetting a proper margin is crucial for not only delivering the required radiation dose to a target volume, but also reducing the unnecessary radiation to the adjacent organs at risk. This study investigated the independent one-dimensional symmetric and asymmetric margins between the clinical target volume (CTV) and the planning target volume (PTV) for linac-based single-fraction frameless stereotactic radiosurgery (SRS).nnnMETHODSnThe authors assumed a Dirac delta function for the systematic error of a specific machine and a Gaussian function for the residual setup errors. Margin formulas were then derived in details to arrive at a suitable CTV-to-PTV margin for single-fraction frameless SRS. Such a margin ensured that the CTV would receive the prescribed dose in 95% of the patients. To validate our margin formalism, the authors retrospectively analyzed nine patients who were previously treated with noncoplanar conformal beams. Cone-beam computed tomography (CBCT) was used in the patient setup. The isocenter shifts between the CBCT and linac were measured for a Varian Trilogy linear accelerator for three months. For each plan, the authors shifted the isocenter of the plan in each direction by ±3 mm simultaneously to simulate the worst setup scenario. Subsequently, the asymptotic behavior of the CTV V80% for each patient was studied as the setup error approached the CTV-PTV margin.nnnRESULTSnThe authors found that the proper margin for single-fraction frameless SRS cases with brain cancer was about 3 mm for the machine investigated in this study. The isocenter shifts between the CBCT and the linac remained almost constant over a period of three months for this specific machine. This confirmed our assumption that the machine systematic error distribution could be approximated as a delta function. This definition is especially relevant to a single-fraction treatment. The prescribed dose coverage for all the patients investigated was 96.1% ± 5.5% with an extreme 3-mm setup error in all three directions simultaneously. It was found that the effect of the setup error on dose coverage was tumor location dependent. It mostly affected the tumors located in the posterior part of the brain, resulting in a minimum coverage of approximately 72%. This was entirely due to the unique geometry of the posterior head.nnnCONCLUSIONSnMargin expansion formulas were derived for single-fraction frameless SRS such that the CTV would receive the prescribed dose in 95% of the patients treated for brain cancer. The margins defined in this study are machine-specific and account for nonzero mean systematic error. The margin for single-fraction SRS for a group of machines was also derived in this paper.

The Treatment of Extensive Scalp Lesions Combining Electrons with Intensity-Modulated Photons

This study was to investigate the feasibility and potential benefits of combining electrons with intensity modulated photons (IMRT+e) for patients with extensive scalp lesions. A case of a patient with an extensive scalp lesion, in which the target volume covered the entire front half of the scalp, is presented. This approach incorporated the electron dose into the inverse treatment planning optimization. The resulting doses to the planning target volume (PTV) and relevant critical structures were compared. Thermoluminescent dosimeters (TLD), diodes, and GAFCHROMIC EBT films were used to verify the accuracy of the techniques. The IMRT+e plan produced a superior dose distribution to the patient as compared to the IMRT plan in terms of reduction of the dose to the brain with the same dose conformity and homogeneity in the target volumes. This study showed that IMRT+e is a viable treatment modality for extensive scalp lesions patients. It provides a feasible alternative to existing treatment techniques, resulting in improved homogeneity of dose to the PTV compared to conventional electron techniques and a decrease in dose to the brain compared to photon IMRT alone

Femoral fracture risk assessment after intensity modulated radiation therapy (IMRT) for the treatment of soft tissue sarcoma using a novel mathematical model.

Intensity modulated radiation therapy (IMRT) is often used for the treatment of soft tissue sarcoma. Due to high radiation doses, many patients have high risk of suffering from a femoral bone fracture sometime following the IMRT treatment. The most common type of radiation treatment-related fracture is a stress fracture. The fracture risk rate may be as high as 24% in sarcoma patients who have undergone periosteal stripping and received chemotherapy. Thus, it is necessary to be able to identify those patients with high risk for IMRT treatment-related bone fracture. In this paper, we will first present IMRT treatment planning techniques. We will then discuss how bone system changes their stiffness and how the fracture risk develops after a certain period of time post radiation treatment. Finally, we will present our latest data on the femoral bone fracture risk factor assessment for patients with soft tissue sarcoma following IMRT treatment. We have developed a novel mathematical model of trabecular bone composed of a disordered cubic network. Based on our preliminary data, we believe that this new mathematical model could shed new light on the relationship between the femoral bone fracture risk factor and the radiation dose delivered by an IMRT plan and provide a valuable prognostic tool for these high-risk patients

Rotation effects on the target-volume margin determination.

Rotational setup errors are usually neglected in most clinical centers. An analytical formula is developed to determine the extra margin between clinical target volume (CTV) and planning target volume (PTV) to account for setup errors. The proposed formula corrects for both translational and rotational setup errors and then incorporated into margin determination for PTV.

Feasibility study of real-time planning for stereotactic radiosurgery.

PURPOSEn3D rotational setup errors in radiotherapy are often ignored by most clinics due to inability to correct or simulate them accurately and efficiently. There are two types of rotation-related problems in a clinical setting. One is to assess the affected dose distribution in real-time if correction is not applied and the other one is to correct the rotational setup errors prior to the initiation of the treatment. Here, the authors present the analytical solutions to both problems.nnnMETHODSn(1) To assess the real-time dose distribution, eight stereotactic radiosurgery (SRS) cases were used as examples. For each plan, two new sets of beams with different table, gantry, and collimator angles were given in analytical forms as a function of patient rotational errors. The new beams simulate the rotational effects of the patient during the treatment setup. By using one arbitrary set of beams, SRS plans were recomputed with a series of different combinations of patient rotational errors, ranging from (-5°, -5°, -5°) to (5°, 5°, 5°) (roll, pitch, and yaw) with an increment of 1° and compared with those without rotational errors. For each set of rotational errors, its corresponding equivalent beams were computed using the analytical solutions and then used for dose calculation. (2) To correct for the rotational errors, two new sets of table, gantry, and collimator angles were derived analytically to validate the previously published derivation. However, in the derivation, a novel methodology was developed and two sets of table, gantry, and collimator angles were obtained in analytical forms. The solutions provide an alternative approach to rotational error correction by rotating the couch, gantry, and collimator rather than the patient.nnnRESULTSnFor demonstration purpose, the above-derived new beams were implemented in a treatment planning system (TPS) to study the rotational effects on the SRS cases. For each case, the authors have generated ten additional plans that accounted for different rotations of the patient. They have found that rotations have an insignificant effect on the minimal, maximum, mean doses, and V80% of the planning target volume (PTV) when the rotations were relatively small. This was particularly true for the small and near-spherical targets. They, however, did change V95% significantly when the rotations approached 5°. The theory has been validated with clinical SRS cases and proven to be practical and viable. The preliminary results demonstrate that the rotational effects are patient-specific and depend on several important factors, such as the PTV size, the PTV location, and the beam configuration. The solutions given in this paper are of great potential values in clinical applications.nnnCONCLUSIONSnThey have derived the analytical solutions to a new set of table, gantry, and collimator angles for a given treatment beam configuration as a function of patient rotational errors. One solution was used to assess the dosimetric effects of an imperfect patient setup and the other one was used to correct for the setup errors without rotating the patient. Compared to the widely adopted method of rotation effect assessment by importing the rotational CT images into TPS, the equivalent beam approach is simple and accurate. The analytical solutions to correcting for rotational setup errors prior to treatment were also derived. Based on the initial clinical investigations, they firmly believe that clinically viable real-time treatment planning and adaptive radiation therapy are feasible with this novel method.

Estimating dose to implantable cardioverter-defibrillator outside the treatment fields using a skin QED diode, optically stimulated luminescent dosimeters, and LiF thermoluminescent dosimeters

The purpose of this work was to determine the relative sensitivity of skin QED diodes, optically stimulated luminescent dosimeters (OSLDs) (microStar™ DOT, Landauer), and LiF thermoluminescent dosimeters (TLDs) as a function of distance from a photon beam field edge when applied to measure dose at out-of-field points. These detectors have been used to estimate radiation dose to patients implantable cardioverter-defibrillators (ICDs) located outside the treatment field. The ICDs have a thin outer case made of 0.4- to 0.6-mm-thick titanium (∼2.4-mm tissue equivalent). A 5-mm bolus, being the equivalent depth of the devices under the patients skin, was placed over the ICDs. Response per unit absorbed dose-to-water was measured for each of the dosimeters with and without bolus on the beam central axis (CAX) and at a distance up to 20 cm from the CAX. Doses were measured with an ionization chamber at various depths for 6- and 15-MV x-rays on a Varian Clinac-iX linear accelerator. Relative sensitivity of the detectors was determined as the ratio of the sensitivity at each off-axis distance to that at the CAX. The detector sensitivity as a function of the distance from the field edge changed by ± 3% (1-11%) for LiF TLD-700, decreased by 10% (5-21%) for OSLD, and increased by 16% (11-19%) for the skin QED diode (Sun Nuclear Corp.) at the equivalent depth of 5 mm for 6- or 15-MV photon energies. Our results showed that the use of bolus with proper thickness (i.e., ∼d(max) of the photon energy) on the top of the ICD would reduce the scattered dose to a lower level. Dosimeters should be calibrated out-of-field and preferably with bolus equal in thickness to the depth of interest. This can be readily performed in clinic.

Comparison of Two Treatment Approaches for Prostate Cancer: Combined Intensity Modulated Radiation Therapy with 125I Seed Implant Brachytherapy and 125I Seed Implant Brachytherapy alone

The purpose of the present study was to assess the results of two different treatment approaches for clinically localized prostate cancer: intensity‐modulated radiation therapy (IMRT) followed by I125 seed‐implant brachytherapy and I125 seed‐implant brachytherapy alone. We studied our 30 most recent consecutive patients. The sample population consisted of 15 cases treated with IMRT (50.4 Gy) followed by I125 seed‐implant boost (95 Gy), and 15 cases treated with I125 seed implant only (144 Gy). We analyzed established dosimetric indices and various clinical parameters. In addition, we also evaluated and compared the acute urinary morbidities of the two treatment approaches, as assessed by the international prostate symptom score (IPSS). In our series, acute urinary morbidity was slightly increased with IMRT followed by I125 seed‐implant brachytherapy as compared with I125 seed‐implant brachytherapy alone. In addition, we observed no statistically significant correlation between the IPSS and the maximum or mean urethral dose. The combination of IMRT and seed‐implant brachytherapy presents an alternative opportunity to treat clinically localized prostate cancer. The full potential of the procedure needs to be further investigated. PACS number: 87.53.Tf

Inter-Modality Variation in Gross Tumor Volume Delineation in 18FDG-PET Guided IMRT Treatment Planning for Lung Cancer

Rapid advances in 18FDG-PET/CT technology and novel co-registration algorithms have created a strong interest in 18 FDG-PET/CTs application in intensity modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT). Accurate target volume delineation, particularly identification of pathologically positive lymph nodes, could translate into favorable treatment outcome. However, gross tumor volume (GTV) delineation on both CT and 18FDG-PET is very sensitive to observer variation. The objectives of the study were to investigate the inter-modality variation in gross tumor volume delineation defined by two imaging modalities for lung cancer: CT and 18FDG-PET/CT and its dosimetric implications in intensity modulated radiation therapy (IMRT)

From Intensity Modulated Radiation Therapy to 4D Radiation Therapy - An Advance in Targeting Mobile Lung Tumors

Intensity modulated radiation therapy (IMRT) has been widely used in the treatment of lung cancer. The highly conformal dose distribution with steep gradients could miss the target if respiratory motion is not carefully considered during the treatment planning. The issue becomes particularly critical when dose escalation technique is used. To account for this periodical respiratory motion, the common practice is to add an empirical population-based safety margin to the clinical target volume (CTV). However, such a uniform margin does not reflect the fact that respiratory motion is not isotropic. In addition, it is not tailored to each individual patient. Thus, it is not optimal in both tumor targeting and normal tissue sparing. Here, we present our approach to 4D radiation therapy using the Bellows tracking system for targeting mobile lung tumors. The objective was to develop a clinically viable procedure for routine 4D treatment planning.