Biomedical subjects

Bruce H Hasegawa

Publications and source records attributed to Bruce H Hasegawa.

12 recordsLinked to original sources

PubMed2006

A multipinhole small animal SPECT system with submillimeter spatial resolution.

Single photon emission computed tomography (SPECT) is an important technology for molecular imaging studies of small animals. In this arena, there is an increasing demand for high performance imaging systems that offer improved spatial resolution and detection efficiency. We have designed a multipinhole small animal imaging system based on position sensitive avalanche photodiode (PSAPD) detectors with the goal of submillimeter spatial resolution and high detection efficiency, which will allow us to minimize the radiation dose to the animal and to shorten the time needed for the imaging study. Our design will use 8 x 24 mm2 PSAPD detector modules coupled to thallium-doped cesium iodide [CsI(Tl)] scintillators, which can achieve an intrinsic spatial resolution of 0.5 mm at 140 keV. These detectors will be arranged in rings of 24 modules each; the animal is positioned in the center of the 9 stationary detector rings which capture projection data from the animal with a cylindrical tungsten multipinhole collimator. The animal is supported on a bed which can be rocked about the central axis to increase angular sampling of the object. In contrast to conventional SPECT pinhole systems, in our design each pinhole views only a portion of the object. However, the ensemble of projection data from all of the multipinhole detectors provide angular sampling that is sufficient to reconstruct tomographic data from the object. The performance of this multipinhole PSAPD imaging system was simulated using a ray tracing program that models the appropriate point spread functions and then was compared against the performance of a dual-headed pinhole SPECT system. The detection efficiency of both systems was simulated and projection data of a hot rod phantom were generated and reconstructed to assess spatial resolution. Appropriate Poisson noise was added to the data to simulate an acquisition time of 15 min and an activity of 18.5 MBq distributed in the phantom. Both sets of data were reconstructed with an ML-EM reconstruction algorithm. In addition, the imaging performance of both systems was evaluated with a uniformity phantom and a realistic digital mouse phantom. Simulations show that our proposed system produces a spatial resolution of 0.8 mm and an average detection efficiency of 630 cps/MBq. In contrast, simulations of the dual-headed pinhole SPECT system produce a spatial resolution of 1.1 mm and an average detection efficiency of 53 cps/MBq. These results suggest that our novel design will achieve high spatial resolution and will improve the detection efficiency by more than an order of magnitude compared to a dual-headed pinhole SPECT system. We expect that this system can perform SPECT with submillimeter spatial resolution, high throughput, and low radiation dose suitable for in vivo imaging of small animals.

Animals↗

PubMed2006

Progress in SPECT/CT imaging of prostate cancer.

Prostate cancer is the most common type of cancer (other than skin cancer) among men in the United States. Although prostate cancer is one of the few cancers that grow so slowly that it may never threaten the lives of some patients, it can be lethal once metastasized. Indium-111 capromab pendetide (ProstaScint, Cytogen Corporation, Princeton, NJ) imaging is indicated for staging and recurrence detection of the disease, and is particularly useful to determine whether or not the disease has spread to distant metastatic sites. However, the interpretation of 111In-capromab pendetide is challenging without correlated structural information mostly because the radiopharmaceutical demonstrates nonspecific uptake in the normal vasculature, bowel, bone marrow, and the prostate gland. We developed an improved method of imaging and localizing 111In-Capromab pendetide using a SPECT/CT imaging system. The specific goals included: i) development and application of a novel iterative SPECT reconstruction algorithm that utilizes a priori information from coregistered CT; and ii) assessment of clinical impact of adding SPECT/CT for prostate cancer imaging with capromab pendetide utilizing the standard and novel reconstruction techniques. Patient imaging studies with capromab pendetide were performed from 1999 to 2004 using two different SPECT/CT scanners, a prototype SPECT/CT system and a commercial SPECT/CT system (Discovery VH, GE Healthcare, Waukesha, WI). SPECT projection data from both systems were reconstructed using an experimental iterative algorithm that compensates for both photon attenuation and collimator blurring. In addition, the data obtained from the commercial system were reconstructed with attenuation correction using an OSEM reconstruction supplied by the camera manufacturer for routine clinical interpretation. For 12 sets of patient data, SPECT images reconstructed using the experimental algorithm were interpreted separately and compared with interpretation of images obtained using the standard reconstruction technique. The experimental reconstruction algorithm improved spatial resolution, reduced streak artifacts, and yielded a better correlation with anatomic details of CT in comparison to conventional reconstruction methods (e.g., filtered back-projection or OSEM with attenuation correction only). Images produced with the experimental algorithm produced a subjective improvement in the confidence of interpretation for 11 of 12 studies. There were also changes in interpretations for 4 of 12 studies although the changes were not sufficient to alter prognosis or the patient treatment plan.

Algorithms↗

PubMed2006

A novel approach to multipinhole SPECT for myocardial perfusion imaging.

UNLABELLED: Myocardial perfusion imaging with SPECT remains critically important for diagnosing, assessing, and evaluating treatment of coronary artery disease. However, conventional rotational SPECT suffers from prolonged study times because of relatively low detection efficiency. We therefore have investigated a multipinhole collimator that could improve the detection efficiency in cardiac SPECT by a factor 5, while providing image quality comparable to standard rotational SPECT techniques using parallel-hole collimation. METHODS: We have measured the spatial resolution and efficiency of a 9-pinhole and a parallel-hole collimator mounted to a standard nuclear medicine gamma-camera as a function of distance from the collimator with a point source array. The efficiency was derived by integrating the detected counts, and the spatial resolution was determined from the full width at half maximum of the detected point spread function. In addition, we generated and reconstructed projection data of a 9-pinhole collimator from a digital heart phantom with a basal lesion. We simulated 3 scenarios: single view from left anterior, 2 views from left anterior and left lateral; and 4 views that include the 2 previous views and left lateral and anterior views. RESULTS: We found that the spatial resolution of the 9-pinhole collimator with 8-mm diameter pinholes was 30% poorer than that for the parallel-hole collimator, whereas the detection efficiency was increased by >10-fold. This predicts that a 9-pinhole collimator having the same spatial resolution as a parallel-hole collimator will have 5 times greater efficiency. Reconstructed data from 1 angular view of the 9-pinhole collimator showed the expected loss of spatial resolution in the longitudinal direction with reduced resolution of the basal lesion. In addition, the tomograms showed distortions in the apical region. In contrast, the reconstructed data from 2 and 4 views of the 9-pinhole collimator demonstrated good lesion definition and also produced images describing the shape and size of the heart more accurately. CONCLUSION: Our results indicate that myocardial multipinhole tomography with 2 or more views offers an image quality and spatial resolution comparable with current rotational SPECT techniques, but with the advantage of a 5-fold increase in efficiency.

Coronary Disease↗

PubMed2005

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%.

Algorithms↗

PubMed2005

Calculation and validation of the use of effective attenuation coefficient for attenuation correction in In-111 SPECT.

Nuclear medicine tracers using 111In as a radiolabel are increasing in their use, especially in the domain of oncologic imaging. In these applications, it often is critical to have the capability of quantifying radionuclide uptake and being able to relate it to the biological properties of the tumor. However, images from single photon emission computed tomography (SPECT) can be degraded by photon attenuation, photon scattering, and collimator blurring; without compensation for these effects, image quality can be degraded, and accurate and precise quantification is impossible. Although attenuation correction for SPECT is becoming more common, most implementations can only model single energy radionuclides such as 99mTc and 123I. Thus, attenuation correction for 111In is challenging because it emits two photons (171 and 245 keV) at nearly equal rates (90.2% and 94% emission probabilities). In this paper, we present a method of calculating a single "effective" attenuation coefficient for the dual-energy emissions of 111In, and that can be used to correct for photon attenuation in radionuclide images acquired with this radionuclide. Using this methodology, we can derive an effective linear attenuation coefficient Micro(eff) and an effective photon energy E(eff) based on the emission probabilities and linear attenuation coefficients of the 111In photons. This approach allows us to treat the emissions from 111In as a single photon with an effective energy of 210 keV. We obtained emission projection data from a tank filled with a uniform solution of 111In. The projection data were reconstructed using an iterative maximum-likelihood algorithm with no attenuation correction, and with attenuation correction assuming photon energies of 171, 245, and 210 keV (the derived E(eff)). The reconstructed tomographic images demonstrate that the use of no attenuation correction, or correction assuming photon energies of 171 or 245 keV introduces inaccuracies into the reconstructed radioactivity distribution when compared against the effective energy method. In summary, this work provides both a theoretical framework and experimental methodology of attenuation correction for the dual-energy emissions from 111In. Although these results are specific to 111In, the foundation could easily be extended to other multiple-energy isotopes.

Biophysical Phenomena↗

PubMed2005

Correction of photon attenuation and collimator response for a body-contouring SPECT/CT imaging system.

UNLABELLED: (111)In-Capromab pendetide imaging is indicated for postprostatectomy patients at risk for residual or recurrent disease. However, this study is complicated by relatively long times for tumor uptake and background washout that require imaging to be performed several days after radiopharmaceutical administration. In addition, (111)In-capromab pendetide demonstrates uptake in normal structures that produce images that are interpreted best using correlation with anatomic imaging. Finally, the visual quality of radionuclide imaging can be improved with corrections for photon attenuation and for the geometric response of the radionuclide collimator. Therefore, we have evaluated the advantages of using a commercially available dual-modality SPECT/CT system. In this article, we evaluate a novel iterative reconstruction algorithm using the SPECT/CT data obtained from phantoms and (111)In-capromab pendetide patient studies. METHODS: Phantom data acquired with the dual-head SPECT camera were reconstructed using both filtered backprojection (FBP) and an iterative maximum-likelihood expectation maximization (MLEM) algorithm incorporating corrections for (a) attenuation coefficient at the effective energy of the radionuclide (either (99m)Tc or (111)In) and (b) collimator response based on experimentally measured depth-dependent spatial resolution of the camera. The collimator response model used the coregistered CT image to estimate the source-target distances produced by the patient-contouring logic of the SPECT camera. Spatial resolution was measured using SPECT images of 2 line sources and uniformity from a uniform cylindric tank. Clinical (111)In-capromab pendetide SPECT/CT data were acquired according to the radiopharmaceutical manufacturer's protocol. Region-of-interest (ROI) analysis of a transverse slice at the level of the sacral base produced mean, median, maximum, and minimum counts per pixel for bone marrow and surrounding soft-tissue ROIs. Ratios of the mean capromab pendetide uptake within marrow to uptake within soft tissue were compared for images reconstructed with FBP versus that obtained from the MLEM method with photon attenuation and collimator response corrections. RESULTS: The source-target distances reconstructed from the patient-specific CT image agreed well with the corresponding values recorded manually from the camera display unit. This information was incorporated into the iterative reconstruction algorithms and improved the quality of SPECT images from phantoms and patients versus SPECT images reconstructed without the depth-dependent collimator response model. Qualitatively, SPECT images reconstructed with corrections for photon attenuation and collimator response showed less background activity and improved target contrast compared with those images reconstructed with FBP. The target-to-background ratio (marrow uptake-to-soft-tissue uptake) was significantly better using MLEM reconstruction than with FBP when mean uptake values were measured. CONCLUSION: A priori anatomic data can be used to enhance the quality of the SPECT image when reconstructed using iterative techniques (e.g., MLEM) that use the CT data to produce a patient-specific attenuation map and a collimator response model based on the body contour produced during the SPECT acquisition.

Algorithms↗

PubMed2004

Radiation dose estimate in small animal SPECT and PET.

Calculations of radiation dose are important in assessing the medical and biological implications of ionizing radiation in medical imaging techniques such as SPECT and PET. In contrast, radiation dose estimates of SPECT and PET imaging of small animals are not very well established. For that reason we have estimated the whole-body radiation dose to mice and rats for isotopes such as 18F, 99mTc, 201Tl, (111)In, 123I, and 125I that are used commonly for small animal imaging. We have approximated mouse and rat bodies with uniform soft tissue equivalent ellipsoids. The mouse and rat sized ellipsoids had a mass of 30 g and 300 g, respectively, and a ratio of the principal axes of 1:1:4 and 0.7:1:4. The absorbed fractions for various photon energies have been calculated using the Monte Carlo software package MCNP. Using these values, we then calculated MIRD S-values for two geometries that model the distribution of activity in the animal body: (a) a central point source and (b) a homogeneously distributed source, and compared these values against S-value calculations for small ellipsoids tabulated in MIRD Pamphlet 8 to validate our results. Finally we calculated the radiation dose taking into account the biological half-life of the radiopharmaceuticals and the amount of activity administered. Our calculations produced S-values between 1.06 x 10(-13) Gy/Bq s and 2.77 x 10(-13) Gy/Bq s for SPECT agents, and 15.0 x 10(-13) Gy/Bq s for the PET agent 18F, assuming mouse sized ellipsoids with uniform source distribution. The S-values for a central point source in an ellipsoid are about 10% higher than the values obtained for the uniform source distribution. Furthermore, the S-values for mouse sized ellipsoids are approximately 10 times higher than for the rat sized ellipsoids reflecting the difference in mass. We reviewed published data to obtain administered radioactivity and residence times for small animal imaging. From these values and our computed S-values we estimated that the whole body dose in small animals ranges between 6 cGy and 90 cGy for mice and between about 1 cGy and 27 cGy for rats. The whole body dose in small animal imaging can be very high in comparison to the lethal dose to mice (LD50/30 approximately 7 Gy). For this reason the dose in small animal imaging should be monitored carefully and the administered activity should be kept to a minimum. These results also underscore the need of further development of instrumentation that improves detection efficiency and reduces radiation dose in small animal imaging.

Algorithms↗

PubMed2003

Pinhole single-photon emission computed tomography for myocardial perfusion imaging of mice.

OBJECTIVES: Although transgenic mice have emerged as powerful experimental models of cardiovascular disease, methods for in vivo phenotypic assessment and characterization remain limited, motivating the development of new instruments for biologic measurement. BACKGROUND: We have developed a single-photon emission computed tomography system with a pinhole collimator (pinhole SPECT) for high-resolution cardiovascular imaging of mice. In this study, we describe a protocol for myocardial perfusion imaging of mice using technetium-99m ((99m)Tc)-sestamibi and demonstrate the feasibility for measurement of perfusion defect size from pinhole SPECT images. METHODS: Mice were anesthetized and injected with 370 MBq (10 mCi) of (99m)Tc-sestamibi. Tomographic projection images were acquired by rotating each mouse in a vertical axis in front of a stationary clinical scintillation camera equipped with a pinhole collimator. BALB/c mice (n = 15) were imaged after the permanent ligation of the left anterior descending coronary artery. The resulting defect size was measured from circumferential profiles of short-axis images. After imaging, the hearts were excised and sectioned to obtain ultra-high resolution digital autoradiographs of (99m)Tc-sestamibi, from which the actual infarct size was determined. RESULTS: Reconstructed image quality was equivalent to that obtained for clinical myocardial perfusion imaging. Linear regression analysis produced a correlation coefficient of 0.83 (p < 0.001) between the measured and actual values of the defect size. CONCLUSIONS: These results demonstrate that myocardial perfusion can be characterized qualitatively and quantitatively in mice using pinhole SPECT.

Animals↗

PubMed2003

X-ray-based attenuation correction for positron emission tomography/computed tomography scanners.

A synergy of positron emission tomography (PET)/computed tomography (CT) scanners is the use of the CT data for x-ray-based attenuation correction of the PET emission data. Current methods of measuring transmission use positron sources, gamma-ray sources, or x-ray sources. Each of the types of transmission scans involves different trade-offs of noise versus bias, with positron transmission scans having the highest noise but lowest bias, whereas x-ray scans have negligible noise but the potential for increased quantitative errors. The use of x-ray-based attenuation correction, however, has other advantages, including a lack of bias introduced from post-injection transmission scanning, which is an important practical consideration for clinical scanners, as well as reduced scan times. The sensitivity of x-ray-based attenuation correction to artifacts and quantitative errors depends on the method of translating the CT image from the effective x-ray energy of approximately 70 keV to attenuation coefficients at the PET energy of 511 keV. These translation methods are usually based on segmentation and/or scaling techniques. Errors in the PET emission image arise from positional mismatches caused by patient motion or respiration differences between the PET and CT scans; incorrect calculation of attenuation coefficients for CT contrast agents or metallic implants; or keeping the patient's arms in the field of view, which leads to truncation and/or beam-hardening (or x-ray scatter) artifacts. Proper interpretation of PET emission images corrected for attenuation by using the CT image relies on an understanding of the potential artifacts. In cases where an artifact or bias is suspected, careful inspection of all three available images (CT and PET emission with and without attenuation correction) is recommended.

Anatomy, Cross-Sectional↗

PubMed2002

Dual-modality imaging of function and physiology.

Dual-modality imaging is a technique in which computed tomography (CT) or magnetic resonance imaging is combined with positron emission tomography or single-photon emission CT to acquire structural and functional images with an integated system. The data are acquired in a single procedure; the patient remains on the scanner table while undergoing both x-ray and radionuclide studies to facilitate correlation between the structural and functional images. The resulting data can aid in localization, enabling more specific diagnosis than can be obtained with a conventional imaging study. In addition, the anatomic information can be used to compensate the correlated radionuclide data for physical perturbations such as photon attenuation, scatter radiation, and partial volume errors. Thus, dual-modality imaging provides a priori information that can improve both the visual quality and the quantitative accuracy of the radionuclide images. Dual-modality imaging systems are also being developed for biologic research involving small animals. Small-animal dual-modality systems offer advantages for measurements that currently are performed invasively with autoradiography and tissue sampling. By acquiring data noninvasively, dual-modality imaging permits serial studies in a single animal, enables measurements to be performed with fewer animals, and improves the statistical quality of the data.

Animals↗

PubMed2002

Performance evaluation of a pinhole SPECT system for myocardial perfusion imaging of mice.

The increasing use of transgenic mice as models of human physiology and disease has motivated the development of dedicated in vivo imaging systems for anatomic and functional characterization of mice as an adjunct to or a replacement for established ex vivo techniques. We have developed a pinhole single photon emission computed tomography (SPECT) system for high resolution imaging of mice with cardiovascular imaging as the primary application. In this work, we characterize the system performance through phantom studies. The spatial resolution and sensitivity were measured from images of a line source and point source, respectively, and were reported for a range of object-to-pinhole distances and pinhole diameters. Tomographic images of a uniform cylindrical phantom, Defrise phantom, and grid phantom were used to characterize the image uniformity and spatial linearity. The uniform phantom image did not contain any ring or reconstruction artifacts, but blurring in the axial direction was evident in the Defrise phantom images. The grid phantom images demonstrated excellent spatial linearity. A novel phantom modeling perfusion of the left ventricle of a mouse was designed and built with perfusion defects of varying sizes to evaluate the system performance for myocardial perfusion imaging of mice. The defect volumes were measured from the pinhole SPECT images and correlated to the actual defect volumes calculated according to geometric formulas. Linear regression analysis produced a correlation coefficient of r = 0.995 (p < 0.001), demonstrating the feasibility for measurement of perfusion defect size in mice using pinhole SPECT. We have performed phantom studies to characterize the spatial resolution, sensitivity, image uniformity, and spatial linearity of the pinhole SPECT system. Measurement of the perfusion defect size is a valuable phenotypic assessment and will be useful for hypothesis testing in murine models of cardiovascular disease.

Animals↗

PubMed2002

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.

Algorithms↗