M.C. Wu

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.

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.

Design of combined X-ray CT and SPECT systems for small animals

The recent development of transgenic mice has motivated the authors to design combined X-ray CT and SPECT systems for small animals. Two different systems are presented to illustrate the design considerations. The first system is based on a third generation X-ray CT with multiple pinhole SPECT using two separate detectors. The second is based on a third generation CT and converging collimator SPECT using a common detector. The first system will have spatial resolution of 0.1 and 0.75 mm for CT and SPECT, respectively, while the second will have resolution of 0.15 and 0.46 mm. Both systems will have reasonable sensitivity for animal imaging. These systems promise near perfect registration of anatomical information with the radionuclide distribution, which can assist in accurate localization of radiopharmaceutical uptake and improve absolute quantitation. These systems have applications in radiopharmaceutical development, tumor dosimetry, and nuclear cardiology.

Evaluation of x-ray detectors for dual-modality CT-SPECT animal imaging

We are developing a bench-top animal scanner that will acquire both functional SPECT images and anatomical CT images with sub-millimeter spatial resolution for both imaging modalities. This paper presents preliminary results from the evaluation of two x-ray detectors for the CT application, and dual SPECT-CT images using one of these detectors. Two phosphor-CMOS x-ray detectors, one with 48 m pixels and 5 cm x 5 cm area and the other with 50 μm pixels and 12 cm x 12 cm area, were evaluated for linearity and dynamic range. Each detector showed linearity over ~ 3 orders of magnitude, which is sufficient for mouse CT imaging. The smaller detector was mounted to an A-SPECT system, along with a custom 50 W x-ray source with focal spot size of ~ 150 μm. Phantoms and mice were scanned sequentially, SPECT followed by CT, and the resulting reconstructed images fused into a single SPECT-CT image. These preliminary results show that the two detectors evaluated for this application can successfully achieve high contrast CT images of mice and similar sized objects.

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.

Prostate thermal therapy with interstitial and transurethral ultrasound applicators : A feasibility study

The purpose of this study was to determine the feasibility of using a transurethral ultrasound applicator in combination with implantable ultrasound applicators for inducing thermal coagulation and necrosis of localized cancer lesions or BPH within the prostate gland. The concept being evaluated is the potential to treat target zones in the anterior and lateral portions of the prostate with the transurethral applicator, while simultaneously treating regions of extracapsular extension and zones in the posterior prostate with the directive implantable applicators in combination with a rectal cooling bolus. Biothermal computer simulations, acoustic characterizations, and in vivo thermal dosimetry experiments were used to evaluate the performance of each applicator type and combinations thereof. The preliminary results of this investigation demonstrate that implantable ultrasound applicators, in combination with a transurethral ultrasound applicator, have the potential to provide thermal coagulation and necrosis of small or large regions within the prostate gland, while sparing thermally sensitive rectal tissue.

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.