Andrew B. Hwang

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 using111 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 the111 In-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.

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.

Dosimetric Evaluation of Automatic Segmentation for Adaptive IMRT for Head-and-Neck Cancer

PURPOSE Adaptive planning to accommodate anatomic changes during treatment requires repeat segmentation. This study uses dosimetric endpoints to assess automatically deformed contours. METHODS AND MATERIALS Sixteen patients with head-and-neck cancer had adaptive plans because of anatomic change during radiotherapy. Contours from the initial planning computed tomography (CT) were deformed to the mid-treatment CT using an intensity-based free-form registration algorithm then compared with the manually drawn contours for the same CT using the Dice similarity coefficient and an overlap index. The automatic contours were used to create new adaptive plans. The original and automatic adaptive plans were compared based on dosimetric outcomes of the manual contours and on plan conformality. RESULTS Volumes from the manual and automatic segmentation were similar; only the gross tumor volume (GTV) was significantly different. Automatic plans achieved lower mean coverage for the GTV: V95: 98.6 +/- 1.9% vs. 89.9 +/- 10.1% (p = 0.004) and clinical target volume: V95: 98.4 +/- 0.8% vs. 89.8 +/- 6.2% (p < 0.001) and a higher mean maximum dose to 1 cm(3) of the spinal cord 39.9 +/- 3.7 Gy vs. 42.8 +/- 5.4 Gy (p = 0.034), but no difference for the remaining structures. CONCLUSIONS Automatic segmentation is not robust enough to substitute for physician-drawn volumes, particularly for the GTV. However, it generates normal structure contours of sufficient accuracy when assessed by dosimetric end points.

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%.

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.

A new CdZnTe-based gamma camera for high resolution pinhole SPECT

We have developed and tested a pixelated detector for pinhole SPECT. The 80/spl times/80 detector has a pixel size of 2.5/spl times/2.5 mm/sup 2/ and incorporates the room-temperature solid-state semiconductor CdZnTe which offers direct charge conversion and good stopping power for radionuclides used for small animal SPECT. To optimize low energy photon detection, the detector is operated at a temperature of 15/spl plusmn/1/spl deg/C, and has been designed to minimize absorption losses for photons entering the active detector material. The CdZnTe detector demonstrates good uniformity, spatial resolution and energy resolution. Transmission images obtained with an /sup 125/I point source demonstrate its low-energy performance, while dual isotope images were obtained using /sup 99m/Tc and /sup 201/Tl. The detector therefore offers good performance for high-resolution small animal SPECT.

Design and utility of a small animal CT/SPECT system

Recent developments in the genetic engineering of small animals have motivated us to design an in vivo dual-modality CT/SPECT system that can be used to localize and quantify uptake of single-photon radiotracers in mice. The CT system includes a 75-W x-ray tube and a CCD camera, while the radionuclide imager incorporates a CsI(TI) scintillator coupled to a Si photodiode array with interchangeable pinhole collimators. These devices are mounted on a slip-ring gantry to image a 40-mm diameter cylindrical volume, where both modalities share a common field of view without moving the table on which the animal lies horizontally. The calculated modulation transfer function of the radionuclide system exceeds 10% at 1.01p/mm. The spatial resolution of the CT system is 0.1 mm with at scan time of 15 min and a contrast resolution of 1% for soft tissue. The high-resolution CT image can be used to provide a priori information to correct both the visual quality and the quantitative accuracy of the SPECT image. This imaging system and technique is designed for in vivo functional assessments of cancer and cardiovascular disease in small animals.

Physics strategies for sparing neural stem cells during whole‐brain radiation treatments

PURPOSE Currently, there are no successful long-term treatments or preventive strategies for radiation-induced cognitive impairments, and only a few possibilities have been suggested. One such approach involves reducing the dose to neural stem cell compartments (within and outside of the hippocampus) during whole-brain radiation treatments for brain metastases. This study investigates the fundamental physics issues associated with the sparing of neural stem cells during photon radiotherapy for brain metastases. METHODS Several factors influence the stem cell dose: intracranial scattering, collimator leakage, beam energy, and total number of beams. The relative importance of these factors is investigated through a set of radiation therapy plans, which are all variations of an initial 6 MV intensity-modulated radiation therapy (IMRT) plan designed to simultaneously deliver a whole-brain dose of 30 Gy and maximally reduce stem cell compartment dose. Additionally, an in-house leaf segmentation algorithm was developed that utilizes jaw motion to minimize the collimator leakage. RESULTS The plans are all normalized such that 50% of the PTV receives 30 Gy. For the initial 6 MV IMRT plan, 50% of the stem cells receive a dose greater than 6.3 Gy. Calculations indicate that 3.6 Gy of this dose originates from intracranial scattering. The jaw-tracking segmentation algorithm, used in conjunction with direct machine parameter optimization, reduces the 50% stem cell dose to 4.3 and 3.7 Gy for 6 and 10 MV treatment beams, respectively. CONCLUSIONS Intracranial scattering alone is responsible for a large dose contribution to the stem cell compartment. It is, therefore, important to minimize other contributing factors, particularly the collimator leakage, to maximally reduce dose to these critical structures. The use of collimator jaw tracking in conjunction with modern collimators can minimize this leakage.

Attenuation correction of small animal SPECT images acquired with /sup 125/I-iodorotenone

Iodine-125 is an inexpensive and widely available radioisotope that is used frequently in biological experiments. It is also possible to perform small animal imaging experiments with this isotope, although its low photon energy (27.5 keV) may lead to significant photon attenuation. We have developed a method to calibrate x-ray computed tomography (CT) image data in order to use microCT images to provide objective specific attenuation maps that are included in an iterative reconstruction algorithm to correct for photon attenuation. Phantom experiments with iodine-125 show that this method can compensate for the effects of photon attenuation. A uniform phantom (3.8 cm diameter) imaged without attenuation correction has a decrease in image intensity at its center of approximately 25%, but reconstruction with attenuation correction virtually eliminates the decreased image intensity in the center of the phantom. Using /sup 125/I-iodorotenone, an experimental myocardial flow tracer, we demonstrate photon attenuation correction for iodine-125 imaging in a rat. The addition of attenuation correction improves the uniformity of the resulting perfusion images, better matching the results obtained with autoradiography.

Irradiation of the prostate and pelvic lymph nodes with an adaptive algorithm.

PURPOSE The simultaneous treatment of pelvic lymph nodes and the prostate in radiotherapy for prostate cancer is complicated by the independent motion of these two target volumes. In this work, the authors study a method to adapt intensity modulated radiation therapy (IMRT) treatment plans so as to compensate for this motion by adaptively morphing the multileaf collimator apertures and adjusting the segment weights. METHODS The study used CT images, tumor volumes, and normal tissue contours from patients treated in our institution. An IMRT treatment plan was then created using direct aperture optimization to deliver 45 Gy to the pelvic lymph nodes and 50 Gy to the prostate and seminal vesicles. The prostate target volume was then shifted in either the anterior-posterior direction or in the superior-inferior direction. The treatment plan was adapted by adjusting the aperture shapes with or without re-optimizing the segment weighting. The dose to the target volumes was then determined for the adapted plan. RESULTS Without compensation for prostate motion, 1 cm shifts of the prostate resulted in an average decrease of 14% in D-95%. If the isocenter is simply shifted to match the prostate motion, the prostate receives the correct dose but the pelvic lymph nodes are underdosed by 14% ± 6%. The use of adaptive morphing (with or without segment weight optimization) reduces the average change in D-95% to less than 5% for both the pelvic lymph nodes and the prostate. CONCLUSIONS Adaptive morphing with and without segment weight optimization can be used to compensate for the independent motion of the prostate and lymph nodes when combined with daily imaging or other methods to track the prostate motion. This method allows the delivery of the correct dose to both the prostate and lymph nodes with only small changes to the dose delivered to the target volumes.