Martin P. Tornai

Intraoperative probes and imaging probes

Abstract. Intraoperative probes have been employed to assist in the detection and removal of tumors for more than 50 years. For a period of about 40 years, essentially every detector type that could be miniaturized had been tested or at least suggested for use as an intraoperative probe. These detectors included basic Geiger-Müller (GM) tubes, scintillation detectors, and even state-of-the-art solid state detectors. The radiopharmaceuticals have progressed from 32PO4- injections for brain tumors to sophisticated monoclonal antibodies labeled with iodine-125 for colorectal cancers. The early work was mostly anecdotal, primarily interdisciplinary collaborations between surgeons and physical scientists. These collaborations produced a few publications, but never seemed to result in an ongoing clinical practice. In the mid 1980s, several companies offered basic gamma-detecting intraoperative probes as products. This led to the rapid development of radioimmunoguided surgery (RIGS) and sentinel node detection as regularly practiced procedures to assist in the diagnosis and treatment of cancer. In recent years intraoperative imaging probes have been developed. These devices add the ability to see the details of the detected activity, giving the potential of using the technique in a low-contrast environment. Intraoperative probes are now established as clinical devices, they have a commercial infrastructure to support their continued use, and there is ongoing research, both commercial and academic, that would seem to ensure continued progress and renewed interest in this slowly developing field.

Collection of scintillation light from small BGO crystals

We propose to develop a high resolution positron emission tomography (PET) detector designed for animal imaging. The detector consists of a 2-D array of small bismuth germanate (BGO) crystals coupled via optical fibers to a multi-channel photomultiplier tube (MC-PMT). Though this approach offers several advantages over the conventional BGO block design, it does require that a sufficient number of scintillation photons be transported from the crystal, down the fiber and into the PMT. In this study we use simulations and experimental data to determine how to maximize the signal reaching the PMT. This involves investigating factors such as crystal geometry, crystal surface treatment, the use of reflectors, choice of optical fiber, coupling of crystal to the optical fiber and optical fiber properties. Our results indicate that using 2/spl times/2/spl times/10 mm BGO crystals coupled to 30 cm of clad optical fiber, roughly 50 photoelectrons are produced at the PMT photocathode for a 511 keV interaction. This is sufficient to clearly visualize the photopeak and provide adequate timing resolution for PET. Based on these encouraging results, a prototype detector will now be constructed. >

An EM algorithm for estimating SPECT emission and transmission parameters from emission data only

A maximum-likelihood (ML) expectation-maximization (EM) algorithm (called EM-IntraSPECT) is presented for simultaneously estimating single photon emission computed tomography (SPECT) emission and attenuation parameters from emission data alone. The algorithm uses the activity within the patient as transmission tomography sources, with which attenuation coefficients can he estimated. For this initial study, EM-IntraSPECT was tested on computer-simulated attenuation and emission maps representing a simplified human thorax as well as on SPECT data obtained from a physical phantom. Two evaluations were performed. First, to corroborate the idea of reconstructing attenuation parameters from emission data, attenuation parameters (/spl mu/) were estimated with the emission intensities (/spl lambda/) fixed at their true values. Accurate reconstructions of attenuation parameters were obtained. Second, emission parameters /spl lambda/ and attenuation parameters Cl were simultaneously estimated from the emission data alone. In this case there was crosstalk between estimates of /spl lambda/ and /spl mu/ and final estimates of /spl lambda/ and /spl mu/ depended on initial values. Estimates degraded significantly as the support extended out farther from the body, and an explanation for this is proposed. In the EM-IntraSPECT reconstructed attenuation images, the lungs, spine, and soft tissue were readily distinguished and had approximately correct shapes and sizes. As compared with standard EM reconstruction assuming a fix uniform attenuation map, EM-IntraSPECT-provided more uniform estimates of cardiac activity in the physical phantom study and in the simulation study with tight support, but less uniform estimates with a broad support. The new EM algorithm derived here has additional applications, including reconstructing emission and transmission projection data under a unified statistical model.

A 3D gantry single photon emission tomograph with hemispherical coverage for dedicated breast imaging

Abstract A novel tomographic gantry was designed, built and initially evaluated for single photon emission imaging of metabolically active lesions in the pendant breast and near chest wall. Initial emission imaging measurements with breast lesions of various uptake ratios are presented. Methods: A prototype tomograph was constructed utilizing a compact gamma camera having a field-of-view of Results: As iteration number increased for the tomographically measured data at all polar angles, contrasts increased while signal-to-noise ratios (SNRs) decreased in the expected way with OSEM reconstruction. The rollover between contrast improvement and SNR degradation of the lesion occurred at two to three iterations. The reconstructed tomographic data yielded SNRs with or without scatter correction that were >9 times better than the planar scans. There was up to a factor of ∼2.5 increase in total primary and scatter contamination in the photopeak window with increasing tilt angle from 15° to 45°, consistent with more direct line-of-sight of myocardial and liver activity with increased camera polar angle. Conclusion: This new, ultra-compact, dedicated tomographic imaging system has the potential of providing valuable, fully 3D functional information about small, otherwise indeterminate breast lesions as an adjunct to diagnostic mammography.

Evaluation of fully 3-D emission mammotomography with a compact cadmium zinc telluride detector

A compact, dedicated cadmium zinc telluride (CZT) gamma camera coupled with a fully three-dimensional (3-D) acquisition system may serve as a secondary diagnostic tool for volumetric molecular imaging of breast cancers, particularly in cases when mammographic findings are inconclusive. The developed emission mammotomography system comprises a medium field-of-view, quantized CZT detector and 3-D positioning gantry. The intrinsic energy resolution, sensitivity and spatial resolution of the detector are evaluated with Tc-99m (140 keV) filled flood sources, capillary line sources, and a 3-D frequency-resolution phantom. To mimic realistic human pendant, uncompressed breast imaging, two different phantom shapes of an average sized breast, and three different lesion diameters are imaged to evaluate the system for 3-D mammotomography. Acquisition orbits not possible with conventional emission, or transmission, systems are designed to optimize the viewable breast volume while improving sampling of the breast and anterior chest wall. Complications in camera positioning about the patient necessitate a compromise in these two orbit design criteria. Image quality is evaluated with signal-to-noise ratios and contrasts of the lesions, both with and without additional torso phantom background. Reconstructed results indicate that 3-D mammotomography, incorporating a compact CZT detector, is a promising, dedicated breast imaging technique for visualization of tumors <1 cm in diameter. Additionally, there are no outstanding trajectories that consistently yield optimized quantitative lesion imaging parameters. Qualitatively, imaging breasts with realistic torso backgrounds (out-of-field activity) substantially alters image characteristics and breast morphology unless orbits which improve sampling are utilized. In practice, the sampling requirement may be less strict than initially anticipated.

High resolution CsI(Tl)/Si-PIN detector development for breast imaging

High resolution multi-element (8/spl times/8) imaging arrays with collimators, size matched to discrete CsI(TI) scintillator arrays and Si-PIN photodetector arrays (PDAs) were developed as prototypes for larger arrays for breast imaging. Photodetector pixels were each 1.5/spl times/1.5 mm/sup 2/ with 0.25 mm gaps. A 16-element quadrant of the detector was evaluated with a segmented CsI(TI) scintillator array (1.5/spl times/1.5/spl times/6 mm/sup 3/ segments with 0.25 mm septa) coupled to the silicon array. The scintillator thickness of 6 mm corresponds to >85% total gamma efficiency at 140 keV. Pixel energy resolution of <8% FWHM was obtained for Tc-99m (140 keV). Electronic noise was 41 e/sup -/ RMS corresponding to a 3% FWHM contribution to the 140 keV photopeak. Detection efficiency uniformity (/spl plusmn//spl sigma/%) measured with a Tc-99m flood source was 4.3% for a /spl sim/10% energy photopeak window. Spatial resolution was 1.53 mm FWHM and pitch was 1.75 mm as measured from the Co-57 (122 keV) line spread function. Signal to background was 34 and contrast ([max-min]/[max+min]) was 0.94. The energy resolution and spatial characteristics of the new imaging detector exceed those of other scintillator based imaging detectors. A camera based on this technology will allow: (1) Improved Compton scatter rejection; (2) Detector positioning in close proximity to the breast to increase signal to noise; (3) Improved spatial resolution; and (4) Improved efficiency compared to high resolution collimated gamma cameras for the anticipated compressed breast geometries.

Design and development of a fully 3D dedicated x-ray computed mammotomography system

Our effort to implement a volumetric x-ray computed mammotomography (CmT) system dedicated to imaging breast disease comprises: demonstrated development of a quasi-monochromatic x-ray beam providing minimal dose and other optimal imaging figures of merit; new development of a compact, variable field-of-view, fully-3D acquisition gantry with a digital flat-panel detector facilitating more nearly complete sampling of frequency space and the physical breast volume; incorporation of iterative ordered-subsets transmission (OSTR) image reconstruction allowing modeling of the system matrix. Here, we describe the prototype 3D gantry and demonstrate initial system performance. Data collected on the prototype gantry demonstrate the feasibility of using OSTR with realistic reconstruction times. The gantry consists of a rotating W-anode x-ray tube using ultra-thick K-edge filtration, and an ~20x25cm2 digital flat-panel detector located at <60cm SID. This source/detector combination can be shifted laterally changing the location of the central ray relative to the system center-of-rotation, hence changing the effective imaging field-of-view, and is mounted on a goniometric cradle allowing <50° polar tilt, then on a 360° azimuthal rotation stage. Combined, these stages provide for positioning flexibility in a banded region about a sphere, facilitating simple circle-plus-arc-like trajectories, as well as considerably more complex 3D trajectories. Complex orbits are necessary to avoid physical hindrances from the patient while acquiring the largest imaging volume of the breast. The system capabilities are demonstrated with fully-3D reconstructed images of geometric sampling and resolution phantoms, a fabricated breast phantom containing internal features of interest, and a cadaveric breast specimen. This compact prototype provides flexibility in dedicated, fully-3D CmT imaging of healthy and diseased breasts.

Simulation study of a quasi-monochromatic beam for x-ray computed mammotomography

The purpose of this simulation study was to evaluate the feasibility, benefits, and potential operating parameters of a quasi-monochromatic beam from a tungsten-target x-ray source yielding projection images. The application is intended for newly developed cone beam computed mammotomography (CmT) of an uncompressed breast. The value of a near monochromatic x-ray source for a fully 3D CmT application is the expected improved ability to separate tissues with very small differences in attenuation coefficients. The quasi-monochromatic beam is expected to yield enhanced tomographic image quality along with a low dose, equal to or less than that of dual view x-ray mammography. X-ray spectra were generated with a validated projection x-ray simulation tool (XSpect) for a range of tungsten tube potentials (40-100 kVp), filter materials (Z=51-65), and filter thicknesses (10th to 1000th value layer determined at 60 kVp). The breast was modeled from ICRU-44 breast tissue specifications, and a breast lesion was modeled as a 0.5 cm thick mass. The detector was modeled as a digital flat-panel detector with a 0.06 cm thick CsI x-ray absorption layer. Computed figures of merit (FOMs) included the ratio of mean beam energy post-breast to pre-breast and the ratio of lesion contrasts for edge-located and center-located lesions as indices of breast beam hardening, and SNR2/exposure and SNR2/dose as indices of exposure and dose efficiencies. The impact of optimization of these FOMs on lesion contrast is also examined. For all simulated filter materials at each given attenuation thickness [10th, 100th, 500th, 1000th value layers (VLs)], the mean and standard deviation of the pre-breast spectral full-width at tenth-maximum (FWTM) were 16.1 +/- 2.4, 10.3 +/- 2.2, 7.3 +/- 1.4, and 6.5 +/- 1.5 keV, respectively. The change in beam width at the tenth maximum from pre-breast to post-breast spectra ranged from 4.7 to 1.1 keV, for the thinnest and thickest filters, respectively. The higher Z filters (Z=57-63) produced a quasi-monochromatic beam that allowed the widest tube potential operating range (50-70 kVp) while maintaining minimal beam hardening and maximal SNR2/exposure and SNR2/dose, and providing a contrast greater than that obtained in the unfiltered case. Figures of merit improved with increasing filter thickness, with diminishing returns beyond the 500th value layer attenuation level. Operating parameters required to produce optimal spectra, while keeping exposures equal to that of dual view mammography, are within the capability of the commercial x-ray tube proposed for our experimental study, indicating that use of these highly attenuating filters is viable. Additional simulations comparing Mo/Mo, Mo/Rh, and W/Rh target/filter combinations indicate that they exhibit significantly lower SNR2/exposure than the present approach, precluding them from being used for computed mammotomography, while maintaining dose limitations and obtaining sufficient SNR. Beam hardening was also much higher in the existing techniques (17%-42%) than for our technique (2%). Simulations demonstrate that this quasi-monochromatic x-ray technique may enhance tissue separation for a newly developed cone beam computed mammotomography application for an uncompressed breast.

Experimental spectral measurements of heavy K-edge filtered beams for x-ray computed mammotomography

A dual modality computed mammotomography (CmT) and single photon emission computed tomography (SPECT) system for dedicated 3D breast imaging is in development. Using heavy K-edge filtration, the CmT component narrows the energy spectrum of the cone-shaped x-ray beam incident on the patients pendant, uncompressed breast. This quasi-monochromatic beam is expected to improve discrimination of tissue with similar attenuation coefficients while restraining absorbed dose to below that of dual view mammography. Previous simulation studies showed the optimal energy that maximizes dose efficiency for a 50/50% adipose/glandular breast is between 30 and 40 keV. This study experimentally validates these results using pre-breast and post-breast spectral measurements made under tungsten tube voltages between 40 and 100 kVp using filter materials with K-edge values ranging from 15 to 70 keV. Different filter material thicknesses are used, approximately equivalent to the 200th and 500th attenuating value layer (VL) thickness. Cerium (K = 40.4 keV) filtered post-breast spectra for 8-18 cm breasts are measured for a range of breast compositions. Figures of merit include mean beam energy, spectral full-width at tenth-maximum, beam hardening and dose for the range of breast sizes. Measurements corroborate simulation results, indicating that for a given dose, a 200th VL of cerium filtration may have optimal performance in the dedicated mammotomography paradigm.

Design considerations and initial performance of a 1.2 cm/sup 2/ beta imaging intra-operative probe

A novel small area beta (/spl beta//sup /spl plusmn//) detector is under development for nuclear emission imaging of surgically exposed, radiolabeled tumor beds. The imaging device front-end consists of a 0.5 mm thick by 1.25 cm diameter CaF/sub 2/(Eu) scintillator disk coupled to a rigid bundle of 2 mm diameter double clad optical fibers through a polystyrene light diffuser. The detector area (1.2 cm/sup 2/) was determined by the requirement of introducing the probe into small cavities, e.g. during neuro-surgical lesion resection, but large enough to produce images of clinical significance. Flexible back-end optical fibers (1.9 m long) were coupled to the front-end components allowing /spl sim/75 photo-electrons to be detected for mean beta energies of 250 keV, indicating that sufficient signal can be obtained with clinical beta emitters (e.g. /sup 18/F, /sup 131/I). The long flexible fibers guide the scintillation light to a Philips XP1700 series, fiber optic faceplate, Multi-Channel PMT. The parallel MC-PMT outputs are fed into a variable gain, charge divider network and an i-V pre-amplifier/line driver network, whose resulting four outputs are digitized and histogrammed with standard Anger positioning logic. The various components in the imaging chain were evaluated and optimized by both simulations and measurements. Line spread functions measured in the 10.8 mm FOV were 0.50 mm /spl plusmn/0.038 mm and 0.55 mm /spl plusmn/0.065 mm FWHM in X and Y, respectively. A 20% variation in pulse height and minimal variation in spatial resolution was observed. The differential image uniformity was measured to be /spl plusmn/15.6% with /spl sim/150 cts/pixel. Preliminary images show excellent reproduction of phantom activity distributions.