Charles A. Pelizzari

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.

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.

Evaluation of sparse-view reconstruction from flat-panel-detector cone-beam CT

Flat-panel-detector x-ray cone-beam computed tomography (CBCT) is used in a rapidly increasing host of imaging applications, including image-guided surgery and radiotherapy. The purpose of the work is to investigate and evaluate image reconstruction from data collected at projection views significantly fewer than what is used in current CBCT imaging. Specifically, we carried out imaging experiments using a bench-top CBCT system that was designed to mimic imaging conditions in image-guided surgery and radiotherapy; we applied an image reconstruction algorithm based on constrained total-variation (TV)-minimization to data acquired with sparsely sampled view-angles and conducted extensive evaluation of algorithm performance. Results of the evaluation studies demonstrate that, depending upon scanning conditions and imaging tasks, algorithms based on constrained TV-minimization can reconstruct images of potential utility from a small fraction of the data used in typical, current CBCT applications. A practical implication of the study is that the optimization of algorithm design and implementation can be exploited for considerably reducing imaging effort and radiation dose in CBCT.

Quantitative tumor oxymetric images from 4D electron paramagnetic resonance imaging (EPRI): methodology and comparison with blood oxygen level-dependent (BOLD) MRI.

This work presents a methodology for obtaining quantitative oxygen concentration images in the tumor‐bearing legs of living C3H mice. The method uses high‐resolution electron paramagnetic resonance imaging (EPRI). Enabling aspects of the methodology include the use of injectable, narrow, single‐line triaryl methyl spin probes and an accurate model of overmodulated spectra. Both of these increase the signal‐to‐noise ratio (SNR), resulting in high resolution in space (1 mm)3 and oxygen concentrations (∼3 torr). Thresholding at 15% the maximum spectral amplitude gives leg/tumor shapes that reproduce those in photographs. The EPRI appears to give reasonable oxygen partial pressures, showing hypoxia (∼0–6 torr, 0–103 Pa) in many of the tumor voxels. EPRI was able to detect statistically significant changes in oxygen concentrations in the tumor with administration of carbogen, although the changes were not increased uniformly. As a demonstration of the method, EPRI was compared with nearly concurrent (same anesthesia) T  2* /blood oxygen level‐dependent (BOLD) MRI. There was a good spatial correlation between EPRI and MRI. Homogeneous and heterogeneous T  2* /BOLD MRI correlated well with the quantitative EPRI. This work demonstrates the potential for EPRI to display, at high spatial resolution, quantitative oxygen tension changes in the physiologic response to environmental changes. Magn Reson Med 49:682–691, 2003.

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.

Online repositioning during treatment of the prostate: A study of potential limits and gains☆

PURPOSE With on-line portal imaging devices and image registration tools, the verification of radiation field position prior to each treatment becomes technically feasible. In this paper, we analyze the impact of pre-treatment verification and field position adjustment on target coverage and normal tissue sparing. METHODS AND MATERIALS Port films were compared with corresponding simulation films to determine the magnitude of setup variations in patients treated for prostate cancer. From these data, an analytic function was determined between geometric coverage of the target and field margin size. A paradigm for on-line patient repositioning was employed to generate a new relationship between margin and target coverage. Margins were selected for the situations of normal treatment and on-line repositioning to ensure target coverage. Dose-volume histograms were generated for a typical prostate treatment using these margins. RESULTS On-line repositioning, when setup errors exceed 1 cm, results in a 6 mm reduction in margin, suggesting that 10% of the volume of bladder and rectum may be spared of high dose. CONCLUSION The use of on-line imaging and image registration to guide adjustment of patient setup may lead to a reduction in the volume of normal tissues irradiated, and possibly improve the probability of complication-free survival in future treatments.

Fast iterative algorithms for three‐dimensional inverse treatment planning

Three types of iterative algorithms, algebraic inverse treatment planning (AITP), simultaneous iterative inverse treatment planning (SIITP), and iterative least-square inverse treatment planning (ILSITP), differentiated according to their updating sequences, were generalized to three dimension with true beam geometry and dose model. A rapid ray-tracing approach was developed to optimize the primary beam components. Instead of recalculating the dose matrix at each iteration, the dose distribution was generated by scaling up or down the dose matrix elements of the previous iteration. This significantly increased the calculation speed. The iterative algorithms started with an initial intensity profile for each beam, specified by a two-dimensional pixel beam map of M elements. The calculation volume was divided into N voxels, and the calculation was done by repeatedly comparing the calculated and desired doses and adjusting the values of the beam map elements to minimize an objective function. In AITP, the iteration is performed voxel by voxel. For each voxel, the dose discrepancy was evaluated and the contributing pencil beams were updated. In ILSITP and SIITP, the iteration proceeded pencil beam by pencil beam instead of voxel by voxel. In all cases, the iteration procedure was repeated until the best possible dose distribution was achieved. The algorithms were applied to two examples and the results showed that the iterative techniques were able to produce superior isodose distributions.

Interactive 3-D Patient-Image Registration

A method has been developed which allows accurate registration of 3D image data sets of the head, such as CT or MRI, with with the anatomy of the actual patient. Once registration is accomplished, the patient and image spaces may be interactively explored, and any point or volume of interest in either space instantly transformed to the other. This paper demonstrates the use of this technology in accurately transferring radiation therapy treatment plans from the 3D image space in which they are simulated, to the physical patient. This provides a heretofore missing objective link between 3D image-based simulations and actual treatment delivery.

Comparison of static conformal field with multiple noncoplanar arc techniques for stereotactic radiosurgery or stereotactic radiotherapy

PURPOSE Compare the use of static conformal fields with the use of multiple noncoplanar arcs for stereotactic radiosurgery or stereotactic radiotherapy treatment of intracranial lesions. Evaluate the efficacy of these treatment techniques to deliver dose distributions comparable to those considered acceptable in current radiotherapy practice. METHODS AND MATERIALS A previously treated radiosurgery case of a patient presenting with an irregularly shaped intracranial lesion was selected. Using a three-dimensional (3D) treatment-planning system, treatment plans using a single isocenter multiple noncoplanar arc technique and multiple noncoplanar conformal static fields were generated. Isodose distributions and dose volume histograms (DVHs) were computed for each treatment plan. We required that the 80% (of maximum dose) isodose surface enclose the target volume for all treatment plans. The prescription isodose was set equal to the minimum target isodose. The DVHs were analyzed to evaluate and compare the different treatment plans. RESULTS The dose distribution in the target volume becomes more uniform as the number of conformal fields increases. The volume of normal tissue receiving low doses (> 10% of prescription isodose) increases as the number of static fields increases. The single isocenter multiple arc plan treats the greatest volume of normal tissue to low doses, approximately 1.6 times more volume than that treated by four static fields. The volume of normal tissue receiving high (> 90% of prescription isodose) and intermediate (> 50% of prescription isodose) doses decreases by 29 and 22%, respectively, as the number of static fields is increased from four to eight. Increasing the number of static fields to 12 only further reduces the high and intermediate dose volumes by 10 and 6%, respectively. The volume receiving the prescription dose is more than 3.5 times larger than the target volume for all treatment plans. CONCLUSIONS Use of a multiple noncoplanar conformal static field treatment technique can significantly reduce the volume of normal tissue receiving high and intermediate doses compared with a single isocenter multiple arc treatment technique, while providing a more uniform dose in the target volume. Close conformation of the prescription isodose to the target volume is not possible using static uniform conformal fields for target shapes lacking an axis of rotational symmetry or plane of mirror symmetry.

Late Toxicity After Intensity-Modulated Radiation Therapy for Localized Prostate Cancer: An Exploration of Dose–Volume Histogram Parameters to Limit Genitourinary and Gastrointestinal Toxicity

PURPOSE To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity. METHODS AND MATERIALS In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V(70)), 65 Gy (V(65)), and 40 Gy (V(40)). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. RESULTS With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V(70) ≤ 10%, V(65) ≤ 20%, and V(40) ≤ 40%; 92% for men with rectal V(70) ≤ 20%, V(65) ≤ 40%, and V(40) ≤ 80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged ≥70 years (p = 0.07). No bladder dose-volume relationships were associated with the risk of GU toxicity. CONCLUSIONS IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints may help limit late GI morbidity.