Browsing by Author "Tornai, Martin P"

X-ray mammography is the most widely used breast cancer imaging technique. However, over 400,000 women newly diagnosed each year are misdiagnosed and undergo a biopsy. Current mammography techniques are limited by: (1) low image contrast, especially in women with dense breasts; (2) difficulty in diagnosing and detecting lesions close to the chest wall and in women with radiographically dense breasts; (3) structural overlap onto a two-dimensional (2D) image plane; and (4) patient discomfort due to breast compression. Therefore, three-dimensional (3D) tomographic breast imaging approaches for pendant, uncompressed breasts have been explored to overcome these limitations and improve the detection of breast lesions. The goal of this thesis is to characterize and implement a dual-modality SPECT-CT dedicated breast imaging system that can overcome these limitations and integrate both metabolic and anatomical information to further improve the visual quality and quantitative accuracy over independent systems alone.

Initial work on this thesis started out with characterizing the modulation transfer function (MTF) in 3D for the independent dedicated SPECT and CT systems. Using a novel phantom to measure the MTF at different locations in a 3D reconstructed volume, results show that acquiring images with a step-and-shoot mode and with trajectories that meet the sampling criteria, uniform resolution throughout a 3D reconstructed volume is obtained.

The effects of sampling and system geometry on the reconstructed CT images are investigated. As expected, constraining the x-ray source and detector to a circular tilt yields insufficiently sampled reconstructed images, which contain geometric distortions, reconstruction inaccuracies, and cupping artifacts. Although beam hardening and scatter are considered to be the main causes of cupping artifacts in the reconstructed CT images, this study suggests that insufficient sampling might be a third cause to cupping artifacts in the reconstructed images. An additional finding in this study is that despite the insufficient sampling in the reconstructed CT images, high frequency objects (small size) are preserved more than low frequency objects (large size).

Using a lateral offset geometry (i.e. the entire system shifted such that the central ray of the cone-beam is at an offset with respect to the COR) in CT has also been shown previously to introduce circular and cylindrical artifacts in the reconstructed coronal and sagittal CT slices, respectively. Monte Carlo studies show that these artifacts are due to mechanical detector misalignment. However, cropping the projections, such that there is less of an overlap between conjugate projections, or placing the system in a centered geometry can eliminate these artifacts.

Next, the dual-modality SPECT-CT scanner is designed and built. The performance of this scanner is evaluated with geometric and anthropomorphic phantoms. Despite only nearly complete sampling from both systems, results illustrate that SPECT and CT images can be registered and fused with minimal error.

The feasibility of using the reconstructed CT images to quantify different tissue components is also investigated by using different materials (acrylic, delrin, polyethylene, and fat-equivalent and glandular-equivalent plastics) and a cadaver human breast. By implementing scatter correction using the beam stop approach, scatter corrected reconstructed images yield attenuation coefficient values to within 11% of their actual values.

Finally, few clinical studies are done to evaluate the effectiveness of the dual-modality scanner. Although the CT is currently limited in the amount of breast volume that can be imaged, reconstructed images appear to have minimal distortion and reconstruction inaccuracy. Fused SPECT-CT images also show the significance of using functional information from SPECT to help localize the lesion in the anatomical CT images.

The dual-modality SPECT-CT scanner has successfully demonstrated its capability to uniformly sample an uncompressed breast with 3D complex trajectories that meet the sampling criteria and provide tissue quantification and localization information. This system will be a clinically useful imaging tool in detecting cancer, especially in women with high risk of breast cancer, monitoring treatment therapies, and improving surgical biopsy guidance.

This thesis research builds upon prior work that developed separate SPECT and CT (computed mammotomography, or breast CT) devices that were independently capable of imaging an uncompressed breast in 3D space. To further develop the system as a clinically viable device, it was necessary to integrate the separate imaging systems onto a single gantry, and to simultaneously design a patient-friendly bed that could routinely and effectively position the patient during dual-modality imaging of her uncompressed breast in the system's common field of view. This thesis describes this process and also investigates practical challenges associated with dedicated breast imaging of a prone patient using the integrated SPECT-CT device.

We initially characterized the practicability of implementing the novel x-ray beam ultra-thick K-edge filtration scheme designed for routine use with the breast CT system. Extensive computer simulations and physical measurements were performed to characterize the x-ray beam produced using K-edge filtration with cerium and to compare it to beams produced using other filtration methods and materials. The advantages of using this heavily filtered x-ray beam for uncompressed breast CT imaging were then further evaluated by measuring the dose absorbed by an uncompressed cadaver breast during the course of a routine tomographic scan. It was found that the breast CT device is indeed capable of imaging uncompressed breasts at dose levels below that of the maximum utilized for dual-view screening mammography.

To prepare the separate SPECT and CT systems for integration onto a single platform, the cross contamination of the image of one modality by primary and scattered photons of the complementary modality was quantified. It was found that contamination levels of the emission (SPECT) image by the x-ray transmission source were generally far less than 2% when using photopeak energy windows up to ±8%. In addition, while there was some quantifiable evidence of a variation in the transmission image in response to the presence of 99mTc photons in the patient, the effect of primary and scattered 99mTc photons on the visibility of 5 mm acrylic photons in a low contrast x-ray transmission environment was negligible.

A novel, tiered, stainless steel patient bed was then designed to allow dual-modality imaging using the integrated SPECT-CT system. The performance of the hybrid SPECT-CT system was evaluated during early stage dual-modality patient imaging trials with particular emphasis placed on the performance of the patient bed. The bed was successful in its primary task of enabling dual-modality imaging of a patient's breast in the common field of view, but practical challenges to more effective patient imaging were identified as well as some novel solutions to these challenges.

In the final section of the thesis research, the feasibility of using two of these solutions was investigated with a view to imaging more of the patient's posterior breast volume. Limited angle tomographic trajectories and trajectories that involve raising or lowering the patient bed in mid tomographic acquisition were initially investigated using various geometric phantoms. A very low contrast imaging task was then tested using an observer study to quantify the effect of these trajectories on the ability of observers to maintain visibility of small geometric objects.

This initial integrated SPECT-CT imaging system has demonstrated its ability to successfully perform low dose, dual-modality imaging of the uncompressed breast. Challenges and solutions have been identified here that will make future SPECT-CT designs even more powerful and a clinically relevant technique for molecular imaging of the breast.

The overall goal of this dissertation is to optimize and evaluate the performance of the single photon emission computed tomography (SPECT) subsystem of a dedicated three-dimensional (3D) dual-modality breast imaging system for enhanced semi-automated, quantitative clinical imaging. This novel hybrid imaging system combines functional or molecular information obtained with a SPECT subsystem with high-resolution anatomical imaging obtained with a low dose x-ray Computed Tomography (CT) subsystem. In this new breast imaging paradigm, coined "mammotomography," the subject is imaged lying prone while the individual subsystems sweep 3-dimensionally about her uncompressed, pendant breast, providing patient comfort compared to traditional compression-based imaging modalities along with high fidelity and information rich images for the clinician.

System evaluation includes a direct comparison between dedicated 3D SPECT and dedicated 2D scintimammography imaging using the same high performance, semi-conductor gamma camera. Due to the greater positioning flexibility of the SPECT system gantry, under a wide range of measurement conditions, statistically significantly (p<0.05) more lesions and smaller lesion sizes were detected with dedicated breast SPECT than with compressed breast scintimammography. The importance of good energy resolution for uncompressed SPECT breast imaging was also investigated. Results clearly illustrate both visual and quantitative differences between the various energy windows, with energy windows slightly wider than the system resolution having the best image contrast and quality.

An observer-based contrast-detail study was performed in an effort to evaluate the limits of object detectability under various imaging conditions. The smallest object detail was observed using a 45-degree tilted trajectory acquisition. The complex 3D projected sine wave acquisition, however, had the most consistent combined intra and inter-observer results, making it potentially the best imaging approach for consistent clinical imaging.

Automatic ROR contouring is implemented using a dual-layer light curtain design, ensuring that an arbitrarily shaped breast is within ~1 cm of the camera face, but no closer than 0.5 cm at every projection angle of a scan. Autocontouring enables simplified routine scanning using complex 3D trajectories, and yields improved image quality. Absolute quantification capabilities are also integrated into the SPECT system, allowing the calculation of in vivo total lesion activity. Initial feasibility studies in controlled low noise experiments show promising results with total activity agreement within 10% of the dose calibrator values.

The SPECT system is integrated with a CT scanner for added diagnostic power. Initial human subject studies demonstrate the clinical potential of the hybrid SPECT-CT breast imaging system. The reconstructed SPECT-CT images illustrate the power of fusing functional SPECT information to localize lesions not easily seen in the anatomical CT images. Enhanced quantitative 3D SPECT-CT breast imaging, now with the ability to dynamically contour any sized breast, has high potential to improve detection, diagnosis, and characterization of breast cancer in upcoming larger-scale clinical testing.

The different patient orientations in breast PET/CT and breast MR imaging, supine versus prone, respectively, cause difficulty in integrating and interpreting the data acquired from these two types of imaging protocols. Prone breast PET/CT could be possible provided the assistance of a suitable support. The main purpose of this project is to evaluate the feasibility of prone breast PET/CT imaging using phantoms and to compare this protocol with the standard supine protocol from an image quality perspective. In this project, a rigid, weight-bearing, radiolucent foam support based on the dimensions and layout of the MRI breast coil for prone-pendant clinical breast imaging was devised for prone PET/CT imaging purposes. In order to scan the same test object in various configurations (prone versus supine), breast phantoms were investigated and tested to develop the most suitable combination of materials that can simulate breast morphology. Water-filled intravenous bags were determined to be the best choice for breast phantom development. The breasts containing lesions, along with a torso phantom, were scanned using a clinical PET/CT scanner in both prone and supine orientations. The acquired PET images were quantitatively evaluated in both orientations. Several image quality metrics such as signal-to-noise ratio, local contrast, contrast uniformity, and quantitative repeatability were assessed from the acquired PET data. As a result, prone PET images present better image quality than supine PETv images in terms of SNR and contrast uniformity. However, the uniformity of the signal intensity is worse in prone orientation, and there are several unexpected image artifacts. The paired t-test statistical results suggest that there are significant differences between prone and supine in terms of signal intensity and SNR. It can be concluded that prone PET/CT imaging is geometrically feasible with the assistance of the developed torso support. Prone PET/CT imaging holds advantages over supine PET/CT imaging considering registration with MRI.

The goal of this research was to investigate the feasibility of using a weighted dual-energy subtraction method in dedicated breast CT using quasi-monochromatic x-ray beams, to better distinguish soft tissues in the breast. This research used computer simulations and measurements, includes development of protocols and phantoms, and yields quantitative results and physical components. Quasi-monochromatic beams were created using different specially processed, hermetically sealed ultra-thick K-edge filters yielding a maximum mean energy difference of 7 keV; also, different kVp potentials on the x-ray tube were used with higher atomic number filters, yielding a maximum mean energy difference of 11 keV. A cylindrical phantom containing muscle tissue equivalent material, glandular tissue equivalent material, polyethylene, and acrylic was filled with methanol (adipose tissue equivalent) was developed and scanned to investigate dual-energy contrast enhancement of the different materials. The CT scans were acquired using a dual-modality SPECT-CT system for dedicated breast imaging. The weighted dual-energy subtraction method is adapted from dual-energy x-ray absorptiometry, where a high and low energy CT scan is acquired using two different ultra-thick k-edge filters (or tube potentials) and the data is reconstructed. Region of interest values are obtained from each image, which is then multiplied by a weighted value (k), and the higher energy image is subtracted from the lower energy image to achieve contrast enhancement. The k-values were calculated from the ratio of measured attenuation coefficients for the material to be subtracted. In a projection-noise normalized acquisition scenario, it was found that weighted dual-energy subtraction with quasi-monochromatic beams might not be feasible under the current circumstances due to the especially high noise (poor contrast to noise ratios) and poor contrast. While this was not an optimized scenario, the approach does have promise, indicating that more investigation is needed.

This work investigates phantom and subject positioning as well as collecting data with a variety of angular sampling and acquisition trajectories. The overall goal of this work has been to utilize the dedicated, breast SPECT-CT system to acquire the best possible images. A large portion of this work has been to apply corrections to the system for quantitative imaging. The system has been shown to provide high quality images with minimal out-of-field signal contribution. Additionally, the quantification procedure has been shown to be within 10% of the known activity concentration present at the time of imaging for both VAOR and PROJSINE trajectories.

X-ray mammography has been the gold standard for breast imaging for decades, despite the significant limitations posed by the two dimensional (2D) image acquisitions. Difficulty in diagnosing lesions close to the chest wall and axilla, high amount of structural overlap and patient discomfort due to compression are only some of these limitations. To overcome these drawbacks, three dimensional (3D) breast imaging modalities have been developed including dual modality single photon emission computed tomography (SPECT) and computed tomography (CT) systems. This thesis focuses on the development and integration of the next generation of such a device for dedicated breast imaging. The goals of this dissertation work are to: [1] understand and characterize any effects of fully 3-D trajectories on reconstructed image scatter correction, absorbed dose and Hounsifeld Unit accuracy, and [2] design, develop and implement the fully flexible, third generation hybrid SPECT-CT system capable of traversing complex 3D orbits about a pendant breast volume, without interference from the other. Such a system would overcome artifacts resulting from incompletely sampled divergent cone beam imaging schemes and allow imaging closer to the chest wall, which other systems currently under research and development elsewhere cannot achieve.

The dependence of x-ray scatter radiation on object shape, size, material composition and the CT acquisition trajectory, was investigated with a well-established beam stop array (BSA) scatter correction method. While the 2D scatter to primary ratio (SPR) was the main metric used to characterize total system scatter, a new metric called ‘normalized scatter contribution’ was developed to compare the results of scatter correction on 3D reconstructed volumes. Scatter estimation studies were undertaken with a sinusoidal saddle (±15° polar tilt) orbit and a traditional circular (AZOR) orbit. Clinical studies to acquire data for scatter correction were used to evaluate the 2D SPR on a small set of patients scanned with the AZOR orbit. Clinical SPR results showed clear dependence of scatter on breast composition and glandular tissue distribution, otherwise consistent with the overall phantom-based size and density measurements. Additionally, SPR dependence was also observed on the acquisition trajectory where 2D scatter increased with an increase in the polar tilt angle of the system.

The dose delivered by any imaging system is of primary importance from the patient’s point of view, and therefore trajectory related differences in the dose distribution in a target volume were evaluated. Monte Carlo simulations as well as physical measurements using radiochromic film were undertaken using saddle and AZOR orbits. Results illustrated that both orbits deliver comparable dose to the target volume, and only slightly differ in distribution within the volume. Simulations and measurements showed similar results, and all measured dose values were within the standard screening mammography-specific, 6 mGy dose limit, which is used as a benchmark for dose comparisons.

Hounsfield Units (HU) are used clinically in differentiating tissue types in a reconstructed CT image, and therefore the HU accuracy of a system is very important, especially when using non-traditional trajectories. Uniform phantoms filled with various uniform density fluids were used to investigate differences in HU accuracy between saddle and AZOR orbits. Results illustrate the considerably better performance of the saddle orbit, especially close to the chest and nipple region of what would clinically be a pedant breast volume. The AZOR orbit causes shading artifacts near the nipple, due to insufficient sampling, rendering a major portion of the scanned phantom unusable, whereas the saddle orbit performs exceptionally well and provides a tighter distribution of HU values in reconstructed volumes.

Finally, the third generation, fully-suspended SPECT-CT system was designed in and developed in our lab. A novel mechanical method using a linear motor was developed for tilting the CT system. A new x-ray source and a custom made 40 x 30 cm2 detector were integrated on to this system. The SPECT system was nested, in the center of the gantry, orthogonal to the CT source-detector pair. The SPECT system tilts on a goniometer, and the newly developed CT tilting mechanism allows ±15° maximum polar tilting of the CT system. The entire gantry is mounted on a rotation stage, allowing complex arbitrary trajectories for each system, without interference from the other, while having a common field of view. This hybrid system shows potential to be used clinically as a diagnostic tool for dedicated breast imaging.

The work presented in this dissertation focuses on evaluation of absolute quantification accuracy in dedicated breast SPECT-CT. The overall goal was to investigate through simulations and measurements the impact and utilization of various correction methods for scattered and attenuated photons, characterization of incomplete charge collection in Cadmium Zinc Telluride detectors as a surrogate means of improving scatter correction, and resolution recovery methods for modeling collimator blur during image reconstruction. The quantification accuracy of attenuation coefficients in CT reconstructions was evaluated in geometric phantoms, and a slice-by-slice breast segmentation algorithm was developed to separate adipose and glandular tissue. All correction and segmentation methods were then applied to a pilot study imaging parathyroid patients to determine the average uptake of Tc-99m Sestamibi in healthy breast tissue, including tissue specific uptake in adipose and glandular tissue.

Monte Carlo methods were utilized to examine the changes in incident scatter energy distribution on the SPECT detector as a function of 3D detector position about a pendant breast geometry. A simulated prone breast geometry with torso, heart, and liver was designed. An ideal detector was positioned at various azimuthal and tilted positions to mimic the capabilities of the breast SPECT subsystem. The limited near-photopeak scatter energy range in simulated spectra was linearly fit and the slope used to characterize changes in scatter distribution as a function of detector position. Results show that the detected scatter distribution changes with detector tilt, with increasing incidence of high energy scattered photons at larger detector tilts. However, reconstructions of various simulated trajectories show minimal impact on quantification (<5%) compared to a primary-only reconstruction.

Two scatter compensation methods were investigated and compared to a narrow photopeak-only windowing for quantification accuracy in large uniform regions and small, regional uptake areas: 1) a narrow ±4% photopeak energy window to minimize scatter in the photopeak window, 2) the previously calibrated dual-energy window scatter correction method, and 3) a modified dual-energy window correction method that attempts to account for the effects of incomplete charge collection in Cadmium Zinc Telluride detectors. Various cylindrical phantoms, including those with imbedded hot and cold regions, were evaluated. Results show that the Photopeak-only and DEW methods yield reasonable quantification accuracy (within 10%) for a wide range of activity concentrations and phantom configurations. The mDEW demonstrated highly accurate quantification measurements in large, uniform regions with improved uniformity compared to the DEW method. However, the mDEW method is susceptible to the calibration parameters and the activity concentration of the scanned phantom. The sensitivity of the mDEW to these factors makes it a poor choice for robust quantification applications. Thus, the DEW method using a high-performance CZT gamma camera is still a better choice for quantification purposes

Phantoms studies were performed to investigate the application of SPECT vs CT attenuation correction. Minor differences were observed between SPECT and CT maps when assuming a uniformly filled phantom with the attenuation coefficient of water, except when the SPECT attenuation map volume was significantly larger than the CT volume. Material specific attenuation coefficients reduce the corresponding measured activity concentrations compared to a water-only correction, but the results do not appear more accurate than a water-only attenuation map. Investigations on the impact of image registration show that accurate registration is necessary for absolute quantification, with errors up to 14% observed for 1.5cm shifts.

A method of modeling collimator resolution within the SPECT reconstruction algorithm was investigated for its impact on contrast and quantification accuracy. Three levels of resolution modeling, each with increasing ray-sampling, were investigated. The resolution model was applied to both cylindrical and anthropomorphic breast phantoms with hot and cold regions. Large volume quantification results (background measurements) are unaffected by the application of resolution modeling. For smaller chambers and simulated lesions, contrast generally increases with resolution modeling. Edges of lesions also appear sharper with resolution modeling. No significant differences were seen between the various levels of resolution modeling. However, Gibbs artifacts are amplified at the boundaries of high contrast regions, which can significantly affect absolute quantification measurements. Convergence with resolution modeling is also notably slower, requiring more iterations with OSEM to reach a stable mean activity concentration. Additionally, reconstructions require far more computing time with resolution modeling due to the increase in number of sampling rays. Thus while the edge enhancement and contrast improvements may benefit lesion detection, the artifacts, slower convergence, and increased reconstruction time limit the utility of resolution modeling for both absolute quantification and clinical imaging studies.

Finally, a clinical pilot study was initiated to measure the average uptake of Tc-99m Sestamibi in healthy breast tissue. Subjects were consented from those undergoing diagnostic parathyroid studies at Duke. Each subject was injected with 25mCi of Sestamibi as part of their pre-surgical parathyroid SPECT imaging studies and scanned with the dedicated breast SPECT-CT system before their diagnostic parathyroid SPECT scan. Based on phantom studies of CT reconstructed attenuation coefficient accuracy, a slice-by-slice segmentation algorithm was developed to separate breast CT data into adipose and glandular tissue. SPECT data were scatter, attenuation, and decay corrected to the time of injection. Segmented CT images were used to measure average radiotracer concentration in the whole breast, as well as adipose and glandular tissue. With 8 subjects scanned, the average measured whole breast activity concentration was found to be 0.10µCi/mL. No significant differences were seen between adipose and glandular tissue uptake.

In conclusion, the application of various characterization and correct methods for quantitative SPECT imaging were investigated. Changes in detected scatter distribution appear to have minimal impact on quantification, and characterization of low-energy tailing for a modified scatter subtraction method yields inferior overall quantification results. Comparable quantification accuracy is seen with SPECT and CT-based attenuation maps, assuming the SPECT-based volume is fairly accurate. In general, resolution recovery within OSEM yields higher contrast, but quantification accuracy appears more susceptible to measurement location. Finally, scatter, attenuation, and resolution recovery methods, along with a breast segmentation algorithm, were implemented in a clinical imaging study for quantifying Tc-99m Sestamibi uptake. While the average whole breast uptake was measured to be 0. 10µCi/mL, no significant differences were seen between adipose and glandular tissue or when implementing resolution recovery. Thus, for future clinical imaging, it's recommended that the application of the investigated correction methods should be limited to the traditional DEW method and CT-based attenuation maps for quantification studies.

Using a clinical, dedicated breast SPECT system for low dose 3D molecular breast imaging (MBI) with Tc-99m-sestamibi could be beneficial as functional imaging follow-up to suspicious mammograms. The feasibility of using a readily available, high sensitivity, multi-CZT-detector, clinical cardiac SPECT camera for low dose fully-3D MBI using geometric and anthropomorphic phantoms is investigated.

A stationary, multi-view 19-CZT camera (GE NM530c) using 4.7mm pinhole collimators was utilized for all physical measurements. Reconstructed SPECT spatial resolution and quality field uniformity were evaluated with a planar Cartesian array phantom developed from machineable Styrofoam. Over 100 wells were formed within and extending beyond the reconstructed field of view (FOV) and were filled with 99mTc-pertechnetate point sources. This planar array was stepped through the camera’s FOV; reconstructed images allow the evaluation of the 3D field uniformity. Fillable anthropomorphic breast phantoms (470 to 1730 mL) with inserted fillable lesions (10 mm diameter), attached to a torso phantom, were imaged using different lesion-to-background activity concentrations (from [3:1] to [20:1]), and total acquisition times (30-360 sec) meant to evaluate whether lower injected dose or shorter acquisition times are feasible. To mimic a radiopaque table, a lead sheet and pliable vinyl-coated lead apron, both with a cut-out were placed around the exposed breast of the torso phantom.

The planar array demonstrated good linearity (1.852.7 mm) throughout the FOV. Breast lesion results varied, with a visible 9mm diameter lesion having contrast of at least 0.59 and CNR of 1.18 at [7:1] concentration ratio for all breast sizes, consistent with the expected biological uptake of the radiotracer. Shielding the breast induced a streaking artifact indicating that additional shielding prevents adequate sampling and introduces image artifacts rather than enhance image quality.

While optimization would improve the system for 3D MBI, uncompressed, prone MBI using the current cardiac SPECT scanner is possible due to the spatial accuracy, contrast and CNR characteristics of the reconstructed images for the entire breast volume. There is no need to shield the camera from out-of-field background activity. Measured characteristics of simulated lesions indicate that 1 cm lesions with expected biological uptake should be readily visible in humans.