H.R. Tang

Implementation of a combined X-ray CT-scintillation camera imaging system for localizing and measuring radionuclide uptake: experiments in phantoms and patients

We have developed and demonstrated an imaging system that couples an X-ray CT scanner to a scintillation camera for the localization and absolute measurement of radionuclide uptake. We use the registered CT images to provide physical information to overcome the quantitative errors in nuclear imaging due to attenuation, scatter, and limited spatial resolution. The registration accuracy and precision in phantom experiments was 0.0/spl plusmn/0.4 mm. Preliminary patient scans suggest that the registration techniques developed for phantom studies can be used. Conversion of X-ray CT image data to attenuation maps was accomplished by the scaling of calibration data and includes extensions to account for the presence of iodinated contrast agents. Experimental phantom studies show absolute quantitation with less than 10% error for up to 2:1 target:background activity concentration for objects as small as 2.7 ml. We are evaluating the localization and absolute quantitation of /sup 131/I-MIBG in neuroblastoma patients to determine if the techniques improve correlation between tumor dose and response.

An ultra high resolution ECG-gated myocardial imaging system for small animals

Standard radionuclide imaging systems are of limited use due to their inability to resolve structures in small animals that represent an increasingly important model for the study of cardiovascular disease. The authors are developing an imaging system incorporating a scintillation camera with a pinhole collimator to acquire cardiac gated images of the mouse heart. Through a simulation study, the authors found that the effective diameter of the pinhole was unaffected by the scatter component of photon penetration through the pinhole insert. The authors have performed a myocardial perfusion study with 0.68 FWHM resolution on a normal 25 gram mouse gated at over 400 beats per minute. The authors have demonstrated that it is possible to obtain cardiac-gated, myocardial perfusion images of mice at submillimeter spatial resolution.

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.

Absolute in vivo quantitation of myocardial activity

Quantitation of myocardial SPECT images corrected for attenuation underestimates the true radionuclide content due to partial volume errors. To measure absolute radionuclide uptake, the authors have developed a technique to compensate these images for partial volume errors using coregistered X-ray CT images. The CT image is used to define a template that approximates the geometrical extent of the myocardium. Once defined, the template is assigned unit activity and is mathematically projected using a realistic physical model of the radionuclide imaging process. These projections are then reconstructed and used to compensate the SPECT image for partial volume errors. The method was tested in a porcine model of myocardial perfusion using Tc-99m sestamibi. The in vivo activity concentration in the porcine myocardium had an error in the range -40% to -60% with attenuation correction alone. By also correcting for partial volume errors, absolute quantitation with an accuracy error of 20% or better was achieved.

Use of X-ray CT-defined regions of interest for the determination of SPECT recovery coefficients

For accurate activity per unit volume measurements in SPECT, recovery coefficients are usually applied based on the size and shape of objects being imaged to properly account for the resolution limitations of the gamma camera. Because of noise and limited spatial resolution, determination of object sizes and boundaries can be difficult using the SPECT images alone. The authors therefore have developed a technique which determines activity concentrations for SPECT using regions of interest (ROIs) obtained from coregistered X-ray CT images. In this study, experimental phantoms containing cylindrical and spherical objects were imaged on a combined X-ray CT/SPECT system and reconstructed data volumes were registered using the known geometry of the system. ROIs were defined on the registered CT images and used to help quantify activity concentration in localized regions and to measure object volumes. The authors have derived the recovery curves for these objects and scan technique. They have also tested a technique that demonstrates activity quantitation without the need for object and size dependent recovery coefficients in the case of low background.

Implementation and applications of a combined CT/SPECT system

Combined radionuclide/radiographic (e.g., SPECT/CT, PET/CT) imaging systems are being developed for correlation of structure and function, primarily for assessment of patients with cancer. Another important aspect of these approaches is the possibility of using anatomical data from CT to derive patient-specific compensations for perturbations in the radionuclide data. For example, a patient-specific attenuation map can be derived from CT and incorporated into an iterative reconstruction algorithm to correct the radionuclide image for photon attenuation. In addition, the geometry, location, and configuration of anatomical regions can be determined using CT, from which recovery coefficients or other geometrical factors can be derived to compensate the radionuclide data for errors caused by the limited spatial resolution of radionuclide images. The use of CT to derive correction factors for these perturbations allows combined X-ray/radionuclide imaging techniques to achieve a high degree of accuracy in the absolute quantitation of radiopharmaceuticals.

Development of external fiducial markers for image registration in small animal SPECT/CT

An image registration technique that can be used to register microCT and microSPECT images acquired with a high-resolution dual-modality SPECT/CT small animal imaging system is being developed. External fiducial markers containing droplets of the K/sub 2/HPO/sub 4/ (visible in CT)-/sup 99m/Tc-pertechnetate (visible in SPECT) solution dispersed in narrow-gauge polyethylene tubing were placed on the object prior to imaging. According to phantom measurements, the optimum concentrations of the marker solution were found to be 250 mg/mL for K/sub 2/HPO/sub 4/ and approximately 6-8 mCi/mL for /sup 99m/Tc-pertechnetate. These concentrations were applied for a marker used to register mouse heart phantom images, and were easily visualized in both microSPECT and microCT images.

The effect of radionuclide scatter in emission-transmission CT

In order to assess the relative effect of scatter in comparison to attenuation and collimator blur, we imaged concentric cylinder, cold-lesion, and thorax-like phantoms with the emission-transmission computed tomography (ETCT) system, a novel device capable of both X-ray CT and SPECT. For these experiments, the ETCT system was outfitted with a single channel of low-noise electronics which permitted acquisition of SPECT data with 3 keV FWHM energy resolution for good scatter rejection. Reference images were reconstructed with object-specific attenuation correction and accurate collimator response compensation. These images were then compared to images which were reconstructed without attenuation correction, without collimator response, or with data that had been blurred to simulate 13 keV FWHM energy resolution. The results show that although scatter represents a measurable error, its effect is small compared to the effect of attenuation and collimator blur. As part of this study, we have also compared scatter rejection to the well-known dual energy window scatter correction method and to a technique which incorporates an estimate of the scatter distribution directly in the back-projector of the ML-EM algorithm. It is shown that scatter correction may be preferable to scatter rejection due to noise considerations.

Dual-modality imaging of function and physiology

Dual-modality imaging is a technique where computed tomography or magnetic resonance imaging is combined with positron emission tomography or single-photon computed tomography to acquire structural and functional images with an integrated system. The data are acquired during a single procedure with the patient on a table viewed by both detectors to facilitate correlation between the structural and function images. The resulting data can be useful for localization for more specific diagnosis of disease. In addition, the anatomical 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 be used to improve both the visual quality and the quantitative accuracy of the radionuclide images. Dual-modality imaging systems also are being developed for biological research that involves small animals. The small-animal dual-modality systems offer advantages for measurements that currently are performed invasively using autoradiography and tissue sampling. By acquiring the required data noninvasively, dual-modality imaging has the potential to allow serial studies in a single animal, to perform measurements with fewer animals, and to improve the statistical quality of the data.

An X-ray CT-assisted method for radionuclide activity measurement using planar views

Accurate in vivo measurement of activity is required for dosimetry of internally-administered radionuclides. The authors have developed and demonstrated a technique for the absolute measurement of radionuclide activity that uses registered X-ray CT images to provide physical information for the automated evaluation of planar nuclear images. The registered CT images provide an estimate of the object-specific attenuation with sufficient resolution for the determination of anatomical volumes of interest (VOIs). The CT-derived VOIs are transferred and projected onto the acquired planar nuclear scans using the known geometry of the imaging system and are used to estimate object and background activities on the planar scans. Attenuation is determined directly from the registered and scaled X-ray CT images and is factored into the calculation of the activity. Comparisons of this CT-assisted measurement method to the conjugate-view approach of using a single point source for attenuation compensation have been made experimentally. Both methods provide similar accuracy in studies using small activity-filled objects placed in phantoms. However, an automated, CT-assisted method would reduce the inter-operator variability that arises in clinical practice.