Zhiheng Wang

On-line re-optimization of prostate IMRT plans for adaptive radiation therapy

For intermediate and high risk prostate cancer, both the prostate gland and seminal vesicles are included in the clinical target volume. Internal motion patterns of these two organs vary, presenting a challenge for adaptive treatment. Adaptive techniques such as isocenter repositioning and soft tissue alignment are effective when tumor volumes only exhibit translational shift, while direct re-optimization of the intensity-modulated radiation therapy (IMRT) plan maybe more desirable when extreme deformation or differential positioning changes of the organs occur. Currently, direct re-optimization of the IMRT plan using beamlet (or fluence map) has not been reported. In this study, we report a novel on-line re-optimization technique that can accomplish plan adjustment on-line. Deformable image registration is used to provide position variation information on each voxel along the three dimensions. The original planned dose distribution is used as the goal dose distribution for adaptation and to ensure planning quality. Fluence maps are re-optimized via linear programming, and a plan solution can be achieved within 2 min. The feasibility of this technique is demonstrated with a clinical case with large deformation. Such on-line ART process can be highly valuable with hypo-fractionated prostate IMRT treatment.

Magnetic resonance imaging of anatomic and vascular characteristics in a canine model of human aging

Dogs exhibit both neuroanatomical and cognitive changes as a function of age that parallel those seen in aging humans. This study describes in vivo changes in neuroanatomical and cerebrovascular characteristics of the canine brain as a function of age in a group of dogs ranging from 4 to 15 years old. Dynamic contrast-enhanced magnetic resonance imaging (MRI) was used to measure the kinetics of contrast agents in the brain. Measures of vascular volume and blood-brain barrier (BBB) permeability were derived from a pharmacokinetic analysis. Cortical atrophy and ventricular enlargement were characteristic features of the aged canine brain. Vascular volume did not vary as a function of age and BBB permeability exhibited a nonsignificant increasing trend with age. However, BBB dysfunction was detected in one middle-aged dog that in addition to having unusually large ventricles, demonstrated an early onset of diffuse senile plaques at postmortem. These findings indicate that BBB dysfunction detected by magnetic resonance imaging may be useful for predicting and potentially diagnosing early pathological conditions.

STEREOTACTIC BODY RADIOTHERAPY FOR LESIONS OF THE SPINE AND PARASPINAL REGIONS

PURPOSEnTo describe our experience and clinical strategy for stereotactic body radiotherapy (SBRT) of spinal lesions.nnnMETHODS AND MATERIALSnThirty-two patients with 33 spinal lesions underwent computed tomography-based simulation while free breathing. Gross/clinical target volumes included involved portions of the vertebral body and paravertebral/epidural tumor. Planning target volume (PTV) expansion was 6 mm axially and 3 mm radially; the cord was excluded from the PTV. Biologic equivalent dose was calculated using the linear quadratic model with alpha/beta = 3 Gy. Treatment was linear accelerator based with on-board imaging; dose was adjusted to maintain cord dose within tolerance. Survival, local control, pain, and neurologic status were monitored.nnnRESULTSnTwenty-one patients are alive at 1 year (median survival, 14 months). Median follow-up is 6 months for all patients (7 months for survivors). Mean previous radiotherapy dose to 22 patients was 35 Gy, and median interval was 17 months. Renal (31%), breast, and lung (19% each) were the most common histologic sites. Three SBRT fractions (range, one to four fractions) of 7 Gy (range, 5-16 Gy) were delivered. Median cord and target biologic equivalent doses were 70 Gy(3) and 34.3 Gy(10), respectively. Thirteen patients reported complete and 17 patients reported partial pain relief at 1 month. There were four failures (mean, 5.8 months) with magnetic resonance imaging evidence of in-field progression. No dosimetric parameters predictive of failure were identified. No treatment-related toxicity was seen.nnnCONCLUSIONSnSpinal SBRT is effective in the palliative/re-treatment setting. Volume expansion must ensure optimal PTV coverage while avoiding spinal cord toxicity. The long-term safety of spinal SBRT and the applicability of the linear-quadratic model in this setting remain to be determined, particularly the time-adjusted impact of prior radiotherapy.

Four-dimensional magnetic resonance imaging (4D-MRI) using image-based respiratory surrogate: a feasibility study.

PURPOSEnFour-dimensional computed tomography (4D-CT) has been widely used in radiation therapy to assess patient-specific breathing motion for determining individual safety margins. However, it has two major drawbacks: low soft-tissue contrast and an excessive imaging dose to the patient. This research aimed to develop a clinically feasible four-dimensional magnetic resonance imaging (4D-MRI) technique to overcome these limitations.nnnMETHODSnThe proposed 4D-MRI technique was achieved by continuously acquiring axial images throughout the breathing cycle using fast 2D cine-MR imaging, and then retrospectively sorting the images by respiratory phase. The key component of the technique was the use of body area (BA) of the axial MR images as an internal respiratory surrogate to extract the breathing signal. The validation of the BA surrogate was performed using 4D-CT images of 12 cancer patients by comparing the respiratory phases determined using the BA method to those determined clinically using the Real-time position management (RPM) system. The feasibility of the 4D-MRI technique was tested on a dynamic motion phantom, the 4D extended Cardiac Torso (XCAT) digital phantom, and two healthy human subjects.nnnRESULTSnRespiratory phases determined from the BA matched closely to those determined from the RPM: mean (± SD) difference in phase:u2009-3.9% (± 6.4%); mean (± SD) absolute difference in phase: 10.40% (± 3.3%); mean (± SD) correlation coefficient: 0.93 (± 0.04). In the motion phantom study, 4D-MRI clearly showed the sinusoidal motion of the phantom; image artifacts observed were minimal to none. Motion trajectories measured from 4D-MRI and 2D cine-MRI (used as a reference) matched excellently: the mean (± SD) absolute difference in motion amplitude:u2009-0.3 (± 0.5) mm. In the 4D-XCAT phantom study, the simulated 4D-MRI images showed good consistency with the original 4D-XCAT phantom images. The motion trajectory of the hypothesized tumor matched excellently between the two, with a mean (± SD) absolute difference in motion amplitude of 0.5 (± 0.4) mm. 4D-MRI was able to reveal the respiratory motion of internal organs in both human subjects; superior-inferior (SI) maximum motion of the left kidney of Subject #1 and the diaphragm of Subject #2 measured from 4D-MRI was 0.88 and 1.32 cm, respectively.nnnCONCLUSIONSnPreliminary results of our study demonstrated the feasibility of a novel retrospective 4D-MRI technique that uses body area as a respiratory surrogate.

Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents †

A carcinogen (N‐ethyl‐N‐nitrosourea)‐induced animal tumor model was established to grow malignant and benign breast tumors. In each tumor the pharmacokinetic characteristics were measured by using three contrast agents, gadolinium‐diethylene‐triamine‐pentaacetic acid (Gd‐DTPA; <1 kD), Gadomer‐17 (35 kD), and albumin‐Gd‐DTPA (70–90 kD). Infiltrating ductal carcinomas (IDC) with low, medium, and high Scarf‐Bloom‐Richardson grades and fibroadenomas (FA) were analyzed. We found that Gd‐DTPA could differentiate between FA and malignant tumors, but not between malignant tumors of low and high grades. In contrast, the intermediate size agent Gadomer‐17 could differentiate between high‐grade and low‐grade IDC, but not between low‐grade IDC and FA due to their similar enhancement patterns (despite their different origins). The largest agent, albumin‐Gd‐DTPA, was capable of differentiating both, but the low contrast‐to‐noise ratio was its major technical concern. The results in this breast tumor model suggest that macromolecular agents provide useful information for differential diagnosis among IDCs of various grades, but they do not provide superior information than Gd‐DTPA for differential diagnosis between IDC and FA.J. Magn. Reson. Imaging 1999;9:177–186.

Dosimetric characteristics of Novalis Tx system with high definition multileaf collimator

A new Novalis Tx system equipped with a high definition multileaf collimator (HDMLC) recently became available to perform both image-guided radiosurgery and conventional radiotherapy. It is capable of delivering a highly conformal radiation dose with three energy modes: 6 MV photon energy, 15 MV photon energy, and 6 MV photon energy in a stereotactic radiosurgery mode with 1000 MU/min dose rate. Dosimetric characteristics of the new Novalis Tx treatment unit with the HDMLC are systematically measured for commissioning. A high resolution diode detector and miniion-chamber detector are used to measure dosimetric data for a range of field sizes from 4 x 4 mm to 400 x 400 mm. The commissioned Novalis Tx system has passed the RPC stereotactic radiosurgery head phantom irradiation test. The Novalis Tx system not only expands its capabilities with three energy modes, but also achieves better beam conformity and sharer beam penumbra with HDMLC. Since there is little beam data information available for the new Novalis Tx system, we present in this work the dosimetric data of the new modality for reference and comparison.

ExacTrac X-ray 6 degree-of-freedom image-guidance for intracranial non-invasive stereotactic radiotherapy: Comparison with kilo-voltage cone-beam CT

BACKGROUND AND PURPOSEnTo compare the residual setup errors measured with ExacTrac X-ray 6 degree-of-freedom (6D) and cone-beam computed tomography (CBCT) for a head phantom and patients receiving intracranial non-invasive fractionated stereotactic radiotherapy (SRT).nnnMATERIALS AND METHODSnSetup data were collected on a Novalis Tx treatment unit for an anthropomorphic head phantom and 18 patients with intracranial tumors. Initial corrections were determined and corrected with the ExacTrac system only, and then the residual setup error was determined by means of three different procedures. These procedures included registrations of ExacTrac X-ray images with the corresponding digitally reconstructed radiographs (DRRs) using the ExacTrac 6D fusion, and registrations of CBCT images with the planning CT using both online 3D fusion and offline 6D fusion. The difference in residual setup errors between ExacTrac system and CBCT was computed. The impact of rotations on the difference was evaluated.nnnRESULTSnA modest difference in residual setup errors was found between ExacTrac system and CBCT. The root-mean-square (RMS) of the differences observed for translations was typically <0.5mm for phantom, and <1.5mm for patients, respectively. The RMS of the differences for rotation(s) was however <0.2 degree for phantom, and <1.0 degree for patients, respectively. The impact of rotation on the setup difference was minor but not negligible.nnnCONCLUSIONSnThis study indicates that there is a general agreement between ExacTrac system and CBCT.

Impact of collimator leaf width and treatment technique on stereotactic radiosurgery and radiotherapy plans for intra- and extracranial lesions

BackgroundThis study evaluated the dosimetric impact of various treatment techniques as well as collimator leaf width (2.5 vs 5 mm) for three groups of tumors – spine tumors, brain tumors abutting the brainstem, and liver tumors. These lesions often present challenges in maximizing dose to target volumes without exceeding critical organ tolerance. Specifically, this study evaluated the dosimetric benefits of various techniques and collimator leaf sizes as a function of lesion size and shape.MethodsFifteen cases (5 for each site) were studied retrospectively. All lesions either abutted or were an integral part of critical structures (brainstem, liver or spinal cord). For brain and liver lesions, treatment plans using a 3D-conformal static technique (3D), dynamic conformal arcs (DARC) or intensity modulation (IMRT) were designed with a conventional linear accelerator with standard 5 mm leaf width multi-leaf collimator, and a linear accelerator dedicated for radiosurgery and hypofractionated therapy with a 2.5 mm leaf width collimator. For the concave spine lesions, intensity modulation was required to provide adequate conformality; hence, only IMRT plans were evaluated using either the standard or small leaf-width collimators.A total of 70 treatment plans were generated and each plan was individually optimized according to the technique employed. The Generalized Estimating Equation (GEE) was used to separate the impact of treatment technique from the MLC system on plan outcome, and t-tests were performed to evaluate statistical differences in target coverage and organ sparing between plans.ResultsThe lesions ranged in size from 2.6 to 12.5 cc, 17.5 to 153 cc, and 20.9 to 87.7 cc for the brain, liver, and spine groups, respectively. As a group, brain lesions were smaller than spine and liver lesions. While brain and liver lesions were primarily ellipsoidal, spine lesions were more complex in shape, as they were all concave. Therefore, the brain and the liver groups were compared for volume effect, and the liver and spine groups were compared for shape. For the brain and liver groups, both the radiosurgery MLC and the IMRT technique contributed to the dose sparing of organs-at-risk(OARs), as dose in the high-dose regions of these OARs was reduced up to 15%, compared to the non-IMRT techniques employing a 5 mm leaf-width collimator. Also, the dose reduction contributed by the fine leaf-width MLC decreased, as dose savings at all levels diminished from 4 – 11% for the brain group to 1 – 5% for the liver group, as the target structures decreased in volume. The fine leaf-width collimator significantly improved spinal cord sparing, with dose reductions of 14 – 19% in high to middle dose regions, compared to the 5 mm leaf width collimator.ConclusionThe fine leaf-width MLC in combination with the IMRT technique can yield dosimetric benefits in radiosurgery and hypofractionated radiotherapy. Treatment of small lesions in cases involving complex target/OAR geometry will especially benefit from use of a fine leaf-width MLC and the use of IMRT.

6D image guidance for spinal non-invasive stereotactic body radiation therapy: Comparison between ExacTrac X-ray 6D with kilo-voltage cone-beam CT

PURPOSEnTo investigate setup discrepancies measured with ExacTrac X-ray 6 degree-of-freedom (6D) and cone-beam computed tomography (CBCT) for patients under treatments of stereotactic body radiation therapy (SBRT).nnnMATERIALS AND METHODSnIn this work, phantom and patient studies were performed. In the phantom studies, an anthropomorphic phantom was placed with pre-defined positions, and imaged with ExacTrac X-ray 6D and CBCT to test the accuracy of the imaging systems. In the patient studies, 16 spinal SBRT patient cases were retrospectively analyzed. The patients were initially positioned in customized immobilization cradles and then aligned with ExacTrac X-ray 6D and CBCT. The setup discrepancies were computed and quantitatively analyzed.nnnRESULTSnThis study indicates modest discrepancies between ExacTrac X-ray 6D and CBCT with spinal SBRT. The phantom experiments showed that translational and rotational discrepancies in root-mean-square (RMS) between ExacTrac X-ray 6D and CBCT were, respectively, <1.0mm and <1 degrees . In the retrospective patient studies, translational and rotational discrepancies in RMS between ExacTrac X-ray 6D and CBCT were <2.0mm and <1.5 degrees .nnnCONCLUSIONSnExacTrac X-ray 6D represents a potential alternative to CBCT; however, pre-caution should be taken when only ExacTrac X-ray 6D is used to guide SBRT with small setup margins.

Refinement of Treatment Setup and Target Localization Accuracy Using Three-Dimensional Cone-Beam Computed Tomography for Stereotactic Body Radiotherapy

PURPOSESnTo quantitatively compare two-dimensional (2D) orthogonal kV with three-dimensional (3D) cone-beam CT (CBCT) for target localization; and to assess intrafraction motion with kV images in patients undergoing stereotactic body radiotherapy (SBRT).nnnMETHODS AND MATERIALSnA total of 50 patients with 58 lesions received 178 fractions of SBRT. After clinical setup using in-room lasers and skin/cradle marks placed at simulation, patients were imaged and repositioned according to orthogonal kV/MV registration of bony landmarks to digitally reconstructed radiographs from the planning CT. A subsequent CBCT was registered to the planning CT using soft tissue information, and the resultant residual error was measured and corrected before treatment. Posttreatment 2D kV and/or 3D CBCT images were compared with pretreatment images to determine any intrafractional position changes. Absolute averages, statistical means, standard deviations, and root mean square (RMS) values of observed setup error were calculated.nnnRESULTSnAfter initial setup to external marks with laser guidance, 2D kV images revealed vector mean setup deviations of 0.67 cm (RMS). Cone-beam CT detected residual setup deviations of 0.41 cm (RMS). Posttreatment imaging demonstrated intrafractional variations of 0.15 cm (RMS). The individual shifts in three standard orthogonal planes showed no obvious directional biases.nnnCONCLUSIONSnAfter localization based on superficial markings in patients undergoing SBRT, orthogonal kV imaging detects setup variations of approximately 3 to 4 mm in each direction. Cone-beam CT detects residual setup variations of approximately 2 to 3 mm.