Investigation of the dosimetric accuracy of the isocenter shifting method in prostate cancer patients with and without hip prostheses.

PURPOSE: The use of image guided radiation therapy (IGRT) enables compensation for prostate movement by shifting the treatment isocenter to track the prostate on a daily basis. Although shifting the isocenter can alter the source to skin distances (SSDs) and the effective depth of the target volume, it is commonly assumed that these changes have a negligible dosimetric effect, and therefore, the number of monitor units delivered is usually not adjusted. However, it is unknown whether or not this assumption is valid for patient with hip prostheses, which frequently contain high density materials. METHODS: The authors conducted a retrospective study to investigate dosimetric effect of the isocenter shifting method for prostate patients with and without hip prostheses. For each patient, copies of the prostate volume were shifted by up to 1.5 cm from the original position to simulate prostate movement in 0.5 cm increments. Subsequently, 12 plans were created for each patient by creating a copy of the original plan for each prostate position with the isocenter shifted to track the position of the shifted prostate. The dose to the prostate was then recalculated for each plan. For patients with hip prostheses, plans were created both with and without lateral beam angles entering through the prostheses. RESULTS: Without isocenter shifting to compensate for prostate motion of 1.5 cm, the dose to the 95% of the prostate (D-95%) changed by an average of 30% and by up to 64%. This was reduced to less than 3% with the isocenter shifting method. It was found that for patients with hip prostheses, this technique worked best for treatment plans that avoided beam angles passing through the prostheses. CONCLUSIONS: The results demonstrated that the isocenter shifting method can accurately deliver dose to the prostate even in patients with hip prostheses.

Can positron emission tomography (PET) or PET/Computed Tomography (CT) acquired in a nontreatment position be accurately registered to a head-and-neck radiotherapy planning CT?

PURPOSE: To quantify the uncertainties associated with incorporating diagnostic positron emission tomography/CT (PET/CT) and PET into the radiotherapy treatment-planning process using different image registration tools, including automated and manual rigid body registration methods, as well as deformable image registration. METHODS AND MATERIALS: The PET/CTs and treatment-planning CTs from 12 patients were used to evaluate image registration accuracy. The PET/CTs also were used without the contemporaneously acquired CTs to evaluate the registration accuracy of stand-alone PET. Registration accuracy for relevant normal structures was quantified using an overlap index and differences in the center of mass (COM) positions. For tumor volumes, the registration accuracy was measured using COM positions only. RESULTS: Registration accuracy was better with PET/CT than with PET alone. The COM displacements ranged from 3.2 +/- 0.6 mm (mean +/- 95% confidence interval, for brain) to 8.4 +/- 2.6 mm (spinal cord) for registration with PET/CT data, compared with 4.8 +/- 1.7 mm (brain) and 9.9 +/- 3.1 mm (spinal cord) with PET alone. Deformable registration improved accuracy, with minimum and maximum errors of 1.1 +/- 0.8 mm (brain) and 5.4 +/- 1.4 mm (mandible), respectively. CONCLUSIONS: It is possible to incorporate PET and/or PET/CT acquired in diagnostic positions into the treatment-planning process through the use of advanced image registration algorithms, but precautions must be taken, particularly when delineating tumor volumes in the neck. Acquisition of PET/CT in the treatment-planning position would be the ideal method to minimize registration errors.

Assessment of the sources of error affecting the quantitative accuracy of SPECT imaging in small animals.

Small animal SPECT imaging systems have multiple potential applications in biomedical research. Whereas SPECT data are commonly interpreted qualitatively in a clinical setting, the ability to accurately quantify measurements will increase the utility of the SPECT data for laboratory measurements involving small animals. In this work, we assess the effect of photon attenuation, scatter and partial volume errors on the quantitative accuracy of small animal SPECT measurements, first with Monte Carlo simulation and then confirmed with experimental measurements. The simulations modeled the imaging geometry of a commercially available small animal SPECT system. We simulated the imaging of a radioactive source within a cylinder of water, and reconstructed the projection data using iterative reconstruction algorithms. The size of the source and the size of the surrounding cylinder were varied to evaluate the effects of photon attenuation and scatter on quantitative accuracy. We found that photon attenuation can reduce the measured concentration of radioactivity in a volume of interest in the center of a rat-sized cylinder of water by up to 50% when imaging with iodine-125, and up to 25% when imaging with technetium-99m. When imaging with iodine-125, the scatter-to-primary ratio can reach up to approximately 30%, and can cause overestimation of the radioactivity concentration when reconstructing data with attenuation correction. We varied the size of the source to evaluate partial volume errors, which we found to be a strong function of the size of the volume of interest and the spatial resolution. These errors can result in large (>50%) changes in the measured amount of radioactivity. The simulation results were compared with and found to agree with experimental measurements. The inclusion of attenuation correction in the reconstruction algorithm improved quantitative accuracy. We also found that an improvement of the spatial resolution through the use of resolution recovery techniques (i.e. modeling the finite collimator spatial resolution in iterative reconstruction algorithms) can significantly reduce the partial volume errors.

In vivo imaging of mucosal CD4+ T cells using single photon emission computed tomography in a murine model of colitis.

Immune responses that occur in the context of human infectious and inflammatory diseases are usually studied by sampling cells from peripheral blood, from biopsies, or by end-point harvests at necropsy. These approaches are likely to yield information that is incomplete and/or non-representative. Here, we report the development and validation of a non-invasive method to localize and to quantitate the disposition of specific subpopulations of cells in vivo. In a murine model of dextran sulfate sodium (DSS)-induced colitis, CD4+ T cells were visualized in the colon by single photon emission computed tomography (SPECT-CT) after injection of monoclonal, non-depleting, indium-111 (111In) labeled anti-CD4+ antibodies. The SPECT-CT colon uptake ratio (CUR) was found to correlate (p<0.01) with the number of total CD4+ T cells and with standard measures of pathology (colon length, cell counts, and histopathologic evidence of apoptosis, edema, and cellular infiltrates) as assessed by direct examination of diseased colon. Each of these parameters, including the SPECT-CT signal uptake, increased as a function of DSS dose (p<0.05). We conclude that CT-SPECT imaging using an 111In-labeled anti-CD4+ antibody is reflective of traditional parameters of pathology in this experimental model of murine colitis. This approach should be readily applicable to the imaging of discrete cell subpopulations in non-human primates and in humans, thus augmenting our understanding of infectious diseases and inflammation in vivo.

Attenuation correction for small animal SPECT imaging using x-ray CT data.

Photon attenuation in small animal nuclear medicine scans can be significant when using isotopes that emit lower energy photons such as iodine-125. We have developed a method to use microCT data to perform attenuation corrected small animal single-photon emission computed tomography (SPECT). A microCT calibration phantom was first imaged, and the resulting calibration curve was used to convert microCT image values to linear attenuation coefficient values that were then used in an iterative SPECT reconstruction algorithm. This method was applied to reconstruct a SPECT image of a uniform phantom filled with 125I-NaI. Without attenuation correction, the image suffered a 30% decrease in intensity in the center of the image, which was removed with the addition of attenuation correction. This reduced the relative standard deviation in the region of interest from 10% to 6%.

A leaf sequencing algorithm to enlarge treatment field length in IMRT.

With MLC-based IMRT, the maximum usable field size is often smaller than the maximum field size for conventional treatments. This is due to the constraints of the overtravel distances of MLC leaves and/or jaws. Using a new leaf sequencing algorithm, the usable IMRT field length (perpendicular to the MLC motion) can be mostly made equal to the full length of the MLC field without violating the upper jaw overtravel limit. For any given intensity pattern, a criterion was proposed to assess whether an intensity pattern can be delivered without violation of the jaw position constraints. If the criterion is met, the new algorithm will consider the jaw position constraints during the segmentation for the step and shoot delivery method. The strategy employed by the algorithm is to connect the intensity elements outside the jaw overtravel limits with those inside the jaw overtravel limits. Several methods were used to establish these connections during segmentation by modifying a previously published algorithm (areal algorithm), including changing the intensity level, alternating the leaf-sequencing direction, or limiting the segment field size. The algorithm was tested with 1000 random intensity patterns with dimensions of 21 x 27 cm2, 800 intensity patterns with higher intensity outside the jaw overtravel limit, and three different types of clinical treatment plans that were undeliverable using a segmentation method from a commercial treatment planning system. The new algorithm achieved a success rate of 100% with these test patterns. For the 1,000 random patterns, the new algorithm yields a similar average number of segments of 36.9 +/- 2.9 in comparison to 36.6 +/- 1.3 when using the areal algorithm. For the 800 patterns with higher intensities outside the jaw overtravel limits, the new algorithm results in an increase of 25% in the average number of segments compared to the areal algorithm. However, the areal algorithm fails to create deliverable segments for 90% of these patterns. Using a single isocenter, the new algorithm provides a solution to extend the usable IMRT field length from 21 to 27 cm for IMRT on a commercial linear accelerator using the step and shoot delivery method.

Dual-modality imaging of cancer with SPECT/CT.

Dual-modality imaging is an in vivo diagnostic technique that obtains structural and functional information directly from patient studies in a way that cannot be achieved with separate imaging systems alone. Dual-modality imaging systems are configured by combining computed tomography (CT) with radionuclide imaging (using positron emission tomography (PET) or single-photon emission computed tomography (SPECT)) on a single gantry which allows both functional and structural imaging to be performed during a single imaging session without having the patient leave the imaging system. A SPECT/CT system developed at UCSF is being used in a study to determine if dual-modality imaging offers advantages for assessment of patients with prostate cancer using (111)In-ProstaScint, a radiolabeled antibody for the prostate-specific membrane antigen. (111)In-ProstaScint images are reconstructed using an iterative maximum-likelihood expectation-maximization (ML-EM) algorithm with correction for photon attenuation using a patient-specific map of attenuation coefficients derived from CT. The ML-EM algorithm accounts for the dual-photon nature of the 111In-labeled radionuclide, and incorporates correction for the geometric response of the radionuclide collimator. The radionuclide image then can be coregistered and overlaid in color on a grayscale CT image for improved localization of the functional information from SPECT. Radionuclide images obtained with SPECT/CT and reconstructed using ML-EM with correction for photon attenuation and collimator response improve image quality in comparison to conventional radionuclide images obtained with filtered backprojection reconstruction. These results illustrate the potential advantages of dual-modality imaging for improving the quality and the localization of radionuclide uptake for staging disease, planning treatment, and monitoring therapeutic response in patients with cancer.