George T.Y. Chen

Accurate three-dimensional registration of CT, PET, and/or MR images of the brain.

A surface matching technique has been developed to register multiple imaging scans of the brain in three dimensions, with accuracy on the order of the image pixel sizes. Anatomic information visualized in X-ray CT and magnetic resonance images may be integrated with each other and with functional information from positron emission tomography. Anatomical structures and other volumes of interest may be mapped from one scan to another, and corresponding sections through multiple scans may be directly compared. This capability provides a novel quantitative method to address the fundamental problem of relating structure to function in the brain. Applications include basic and clinical problems in the neurosciences and delivery and assessment of brain tumor therapy.

4D-CT imaging of a volume influenced by respiratory motion on multi-slice CT.

We propose a new scanning protocol for generating 4D-CT image data sets influenced by respiratory motion. A cine scanning protocol is used during data acquisition, and two registration methods are used to sort images into temporal phases. A volume is imaged in multiple acquisitions of 1 or 2 cm length along the cranial-caudal direction. In each acquisition, the scans are continuously acquired for a time interval greater than or equal to the average respiratory cycle plus the duration of the data for an image reconstruction. The x ray is turned off during CT table translation and the acquisition is repeated until the prescribed volume is completely scanned. The scanning for 20 cm coverage takes about 1 min with an eight-slice CT or 2 mins with a four-slice CT. After data acquisition, the CT data are registered into respiratory phases based on either an internal anatomical match or an external respiratory signal. The internal approach registers the data according to correlation of anatomy in the CT images between two adjacent locations in consecutive respiratory cycles. We have demonstrated the technique with ROIs placed in the region of diaphragm. The external approach registers the image data according to an externally recorded respiratory signal generated by the Real-Time Position Management (RPM) Respiratory Gating System (Varian Medical Systems, Palo Alto, CA). Compared with previously reported prospective or retrospective imaging of the respiratory motion with a single-slice or multi-slice CT, the 4D-CT method proposed here provides (1) a shorter scan time of three to six times faster than the single-slice CT with prospective gating; (2) a shorter scan time of two to four times improvement over a previously reported multi-slice CT implementation, and (3) images over all phases of a breathing cycle. We have applied the scanning and registration methods on phantom, animal and patients, and initial results suggest the applicability of both the scanning and the registration methods.

Evaluation of changes in the size and location of the prostate, seminal vesicles, bladder, and rectum during a course of external beam radiation therapy.

PURPOSE To document the size and location of the prostate, seminal vesicles, bladder, and rectum throughout the course of external beam radiotherapy. The frequency and range of motion of these organs are quantified. METHODS AND MATERIALS Ten patients with localized carcinoma of the prostate had conventional simulation followed immediately by a treatment planning computed tomography scan (TPCT0). Once treatment was initiated, each patient had a weekly CT (TPCT1-N) before or after his daily treatment. Anatomical structures from CT were delineated on a computer workstation for analysis. The serial CT sets were spatially registered to the initial scan using image correlation software that brings into congruence the bony pelvis of the different scans. The location of the prostate, seminal vesicles, bladder, and rectum on subsequent scans were compared to TPCT0, as well as to each other. RESULTS Prostate volumes were observed to vary by an average of +/- 10% during the course of radiation therapy, while the seminal vesicle volumes varied by as much as 100%. Bladder and rectal volumes varied by +/- 30%. Compared to TPCT0, movement of the prostate was demonstrated in all patients. Quantitation of the center-of-mass (CM) showed motion of less than 1 mm in the left-right direction, while motion ranging from 0 to +/- 1 cm was observed in the anterior-posterior and superior-inferior directions. The individual standard deviations of these motions varied from approximately 1-5 mm. These variations were correlated to changes in the dimensions of the bladder and rectum. CONCLUSIONS Changes in the location of the prostate, seminal vesicles, and normal tissue volumes during the course of radiation therapy occur and have dosimetric consequences that may impact tumor control and normal tissue complication probabilities. Conformal therapy for prostate cancer will require the incorporation of knowledge of the anatomic relationships of these structures as a function of time. Therefore, these uncertainties must be taken into account when designing treatment plans and in considering dose escalation trials.

Four‐dimensional computed tomography: Image formation and clinical protocol

Respiratory motion can introduce significant errors in radiotherapy. Conventional CT scans as commonly used for treatment planning can include severe motion artifacts that result from interplay effects between the advancing scan plane and object motion. To explicitly include organ/target motion in treatment planning and delivery, time-resolved CT data acquisition (4D Computed Tomography) is needed. 4DCT can be accomplished by oversampled CT data acquisition at each slice. During several CT tube rotations projection data are collected in axial cine mode for the duration of the patients respiratory cycle (plus the time needed for a full CT gantry rotation). Multiple images are then reconstructed per slice that are evenly distributed over the acquisition time. Each of these images represents a different anatomical state during a respiratory cycle. After data acquisition at one couch position is completed, x rays are turned off and the couch advances to begin data acquisition again until full coverage of the scan length has been obtained. Concurrent to CT data acquisition the patients abdominal surface motion is recorded in precise temporal correlation. To obtain CT volumes at different respiratory states, reconstructed images are sorted into different spatio-temporally coherent volumes based on respiratory phase as obtained from the patients surface motion. During binning, phase tolerances are chosen to obtain complete volumetric information since images at different couch positions are reconstructed at different respiratory phases. We describe 4DCT image formation and associated experiments that characterize the properties of 4DCT. Residual motion artifacts remain due to partial projection effects. Temporal coherence within resorted 4DCT volumes is dominated by the number of reconstructed images per slice. The more images are reconstructed, the smaller phase tolerances can be for retrospective sorting. From phantom studies a precision of about 2.5 mm for quasiregular motion and typical respiratory periods could be concluded. A protocol for 4DCT scanning was evaluated and clinically implemented at the MGH. Patient data are presented to elucidate how additional patient specific parameters can impact 4DCT imaging.

An experimental investigation on intra-fractional organ motion effects in lung IMRT treatments

Respiration-induced tumour motion can potentially compromise the use of intensity-modulated radiotherapy (IMRT) as a dose escalation tool for lung tumour treatment. We have experimentally investigated the intra-fractional organ motion effects in lung IMRT treatments delivered by multi-leaf collimator (MLC). An in-house made motor-driven platform, which moves sinusoidally with an amplitude of 1 cm and a period of 4 s, was used to mimic tumour motion. Tumour motion was simulated along cranial-caudal direction while MLC leaves moved across the patient from left to right, as in most clinical cases. The dose to a point near the centre of the tumour mass was measured according to geometric and dosimetric parameters from two five-field lung IMRT plans. For each field, measurement was done for two dose rates (300 and 500 MU min(-1)), three MLC delivery modes (sliding window, step-and-shoot with 10 and 20 intensity levels) and eight equally spaced starting phases of tumour motion. The dose to the measurement point delivered from all five fields was derived for both a single fraction and 30 fractions by randomly sampling from measured dose values of each field at different initial phases. It was found that the mean dose to a moving tumour differs slightly (<2-3%) from that to a static tumour. The variation in breathing phase at the start of dose delivery results in a maximum variation around the mean dose of greater than 30% for one field. The full width at half maximum for the probability distribution of the point dose is up to 8% for all five fields in a single fraction, but less than 1-2% after 30 fractions. In general, lower dose rate can reduce the motion-caused dose variation and therefore might be preferable for lung IMRT when no motion mitigation techniques are used. From the two IMRT cases we studied where tumour motion is perpendicular to MLC leaf motion, the dose variation was found to be insensitive to the MLC delivery mode.

Residual motion of lung tumours in gated radiotherapy with external respiratory surrogates

Due to respiration, many tumours in the thorax and abdomen may move as much as 3 cm peak-to-peak during radiation treatment. To mitigate motion-induced irradiation of normal lung tissue, clinics have employed external markers to gate the treatment beam. This technique assumes that the correlation between the external surface and the internal tumour position remains constant inter-fractionally and intra-fractionally. In this work, a study has been performed to assess the validity of this correlation assumption for external surface based gated radiotherapy, by measuring the residual tumour motion within a gating window. Eight lung patients with implanted fiducial markers were studied at the NTT Hospital in Sapporo, Japan. Synchronized internal marker positions and external abdominal surface positions were measured during the entire course of treatment. Stereoscopic imaging was used to find the internal markers in four dimensions. The data were used retrospectively to assess conventional external surrogate respiratory-gated treatment. Both amplitude- and phase-based gating methods were investigated. For each method, three gating windows were investigated, each giving 40%, 30% and 20% duty cycle, respectively. The residual motion of the internal marker within these six gating windows was calculated. The beam-to-beam variation and day-to-day variation in the residual motion were calculated for both gating modalities. We found that the residual motion (95th percentile) was between 0.7 and 5.8 mm, 0.8 and 6.0 mm, and 0.9 and 6.2 mm for 20%, 30% and 40% duty cycle windows, respectively. Five of the eight patients showed less residual motion with amplitude-based gating than with phase-based gating. Large fluctuations (>300%) were seen in the residual motion between some beams. Overall, the mean beam-to-beam variation was 37% and 42% from the previous treatment beam for amplitude- and phase-based gating, respectively. The day-to-day variation was 29% and 34% from the previous day for amplitude- and phase-based gating, respectively. Although gating reduced the total tumour motion, the residual motion behaved unpredictably. Residual motion during treatment could exceed that which might have been considered in the treatment plan. Treatment margins that account for motion should be individualized and daily imaging should be performed to ensure that the residual motion is not exceeding the planned motion on a given day.

A phantom evaluation of a stereo-vision surface imaging system for radiotherapy patient setup

External beam irradiation requires precise positioning of the target relative to the treatment planning coordinate system. A three-dimensional (3D) surface imaging system for patient positioning has recently been installed in one of our linear accelerator (linac) rooms. The device utilizes close-range photogrammetry to generate a 3D model of the patients surface. This geometric model can be made to look like a digital camera image if wrapped with a gray-level image (texture mapping) that shows surface coloration. The system is calibrated to the linac coordinate system and has been designed as a patient setup device. To reproduce patient position in fractionated radiotherapy, the daily patient surface model is registered to a previously recorded reference surface. Using surface registration, the system calculates the rigid-body transformation that minimizes the distance between the treatment and the reference surface models in a region-of-interest (ROI). This transformation is expressed as a set of new couch coordinates at which the patient position best matches with the reference data. If respiratory motion is a concern, the surface can be obtained with a gated acquisition at a specified phase of the respiratory cycle. To analyze the accuracy of the system, we performed several experiments with phantoms to assess stability, alignment accuracy, precision of the gating function, and surface topology. The reproducibility of surface measurements was tested for periods up to 57 h. Each recorded frame was registered to the reference surface to calculate the required couch adjustment. The system stability over this time period was better than 0.5 mm. To measure the accuracy of the system to detect and quantify patient shift relative to a reference image, we compared the shift detected by the surface imaging system with known couch transitions in a phantom study. The maximum standard deviation was 0.75 mm for the three translational degrees of freedom, and less than 0.1° for each rotation. Surface model precision was tested against computed tomography (CT)-derived surface topology. The root-mean-square rms of the distance between the surfaces was 0.65 mm, excluding regions where beam hardening caused artifacts in the CT data. Measurements were made to test the gated acquisition mode. The time-dependent amplitude was measured with the surface imaging system and an established respiratory gating system based on infrared (IR)-marker detection. The measured motion trajectories from both systems were compared to the known trajectory of the stage. The standard deviations of the amplitude differences to the motor trajectory were 0.04 and 0.15 mm for the IR-marker system and the 3D surface imaging system, respectively. A limitation of the surface-imaging device is the frame rate of 6.5 Hz, because rapid changes of the motion trajectory cannot be detected. In conclusion, the system is accurate and sufficiently stable to be used in the clinic. The errors computed when comparing the surface model with CT geometry were submillimeter, and deviations in the alignment and gating-signal tests were of the same magnitude.

Model-based segmentation of medical imagery by matching distributions

The segmentation of deformable objects from three-dimensional (3-D) images is an important and challenging problem, especially in the context of medical imagery. We present a new segmentation algorithm based on matching probability distributions of photometric variables that incorporates learned shape and appearance models for the objects of interest. The main innovation over similar approaches is that there is no need to compute a pixelwise correspondence between the model and the image. This allows for a fast, principled algorithm. We present promising results on difficult imagery for 3-D computed tomography images of the male pelvis for the purpose of image-guided radiotherapy of the prostate.

Correlation of projection radiographs in radiation therapy using open curve segments and points

A method for determining differences in patient position between projection radiographs such as those routinely used in radiation therapy has been developed. Determination of a transformation relating two radiographs permits registration of simulation and portal images and the transfer of information between them. The algorithm is based on spatially registering segments of open curves or points seen on both images, and does not require identification of corresponding curve endpoints. The method as implemented is both fast and accurate. After user definition of the curves or points to be registered, the optimal transformation is calculated in approximately 1 s. Calculational experiments indicate that corresponding points on open curves are registered to better than 2 mm, even when random errors (FWHM 1 mm) in digitization are included. Experiments on the registration of clinical portal and simulation images (pixel size = 0.5 by 0.5 mm) indicate an accuracy on the order of 2 mm or less in translation and 2 deg or less in rotation. Analysis of portal and simulation radiographs of the brain, thorax, and pelvis indicates this algorithm to be robust and clinically applicable. The rapid and accurate registration of portal and simulation images is potentially important in the application of real time portal imaging devices in radiation therapy.

Proton Beams to Replace Photon Beams in Radical Dose Treatments

With proton beam radiation therapy a smaller volume of normal tissues is irradiated at high dose levels for most anatomic sites than is feasible with any photon technique. This is due to the Laws of Physics, which determine the absorption of energy from photons and protons. In other words, the dose from a photon beam decreases exponentially with depth in the irradiated material. In contrast, protons have a finite range and that range is energy dependent. Accordingly, by appropriate distribution of proton energies, the dose can be uniform across the target and essentially zero deep to the target and the atomic composition of the irradiated material. The dose proximal to the target is lower compared with that in photon techniques, for all except superficial targets. This resultant closer approximation of the planning treatment volume (PTV) to the CTV/GTV (grossly evident tumor volume/subclinical tumor extensions) constitutes a clinical gain by definition; i.e. a smaller treatment volume that covers the target three dimensionally for the entirety of each treatment session provides a clinical advantage. Several illustrative clinical dose distributions are presented and the clinical outcome results are reviewed briefly. An important technical advance will be the use of intensity modulated proton radiation therapy, which achieves contouring of the proximal edge of the SOBP (spread out bragg peak) as well as the distal edge. This technique uses pencil beam scanning. To permit further progressive reductions of the PTV, 4-D treatment planning and delivery is required. The fourth dimension is time, as the position and contours of the tumor and the adjacent critical normal tissues are not constant. A potentially valuable new method for assessing the clinical merits of each of a large number of treatment plans is the evaluation of multidimensional plots of the complication probabilities for each of ‘n’ critical normal tissues/structures for a specified tumor control probability. The cost of proton therapy compared with that of very high technology photon therapy is estimated and evaluated. The differential is estimated to be ≈1.5 provided there were to be no charge for the original facility and that there were sufficient patients for operating on an extended schedule (6–7 days of 14–16 h) with ≥ two gantries and one fixed horizontal beam.