We present an objective analysis and comparison on a level technological playing field of Cancer Detection Rates (CDRs) by performing a meta-analysis from publications about dense breasts using FDA-approved imaging modalities available for supplemental breast cancer screening in the USA. Awareness is growing about the relatively low overall cancer detection rate of digital mammography (DM), digital breast tomosynthesis (DBT) and breast ultrasound (US), especially for the nearly 25 million screening-eligible women with increased breast density (BIRADS C,D). Since a majority of research papers use comparisons to the screening "gold standard" of DM, analysis using pooled CDRs normalized to DM is presented. Other important factors such as the number of theoretical net lives saved using a benefit-to-risk comparison of ionizing imaging modalities is included. Lingering concerns about ionizing radiation dose of supplemental screening options are also discussed with the comparative perspective of the unavoidable yearly background dose every human being receives. This objective, normalized analysis identifies contrast-enhanced mammography (CEM) and molecular breast imaging (MBI) to have Cancer Detection Rates (CDR) within 90% (and greater) of breast magnetic resonance imaging (MRI). These top-three "vascular imaging modalities" each employ injected contrast agents to enhance visualization and facilitate the detection of early-stage breast cancers. By enabling earlier diagnosis with more appropriate supplemental breast imaging, the use of either CEM, MBI or MRI will: decrease mortality; reduce patient's physical, financial and psychological trauma; and reduce costs per cancer detected earlier, with overall benefit to the patients, the hospitals and the payors, thus providing long-term societal benefits.

338 Objectives Molecular Breast Imaging (MBI) uses single gamma photons to visualize breast tumors that are often occult on mammography in women with radiographically dense breasts. Our purpose was to reduce the MBI dose and evaluate MBI9s potential for future screening of women with dense breasts. Methods We optimized the near-field imaging physics for the LumaGEM MBI scanner (Gamma Medica) that uses two detector heads with tiled modules of pixellated CZT gamma detectors with 1.6 mm square pixels. Breasts are mildly immobilized between the two detector heads with 1/3 the compression pressure of mammography to a mean thickness of 6 cm. We designed a low-dose collimator fabricated with tungsten septa and square holes that match the CZT detector pixels. We fuse the images from the two opposed heads to increase SNR and contrast. We developed a 6 cm thick breast lesion phantom with 12 liquid-fillable lesions at several depths and with a warm background volume, which facilitates measurement of contrast-recovery curves, useful for comparison of various MBI systems and for predicting lesion detectability. Results In clinical trials at Mayo Clinic we have demonstrated low-dose MBI with a whole-body dose similar to screening mammography. MBI has proven far more sensitive and specific at detecting biopsy-proven cancers than mammography in dense breasts. The breast lesion phantom demonstrates that our 1.6 mm pixel size is optimal for MBI, enabling the lowest dose compared to other systems using 2.5 mm or 3.2 mm pixels. Conclusions Dose has been effectively mitigated as an obstacle to MBI screening of radiographically dense breasts. Clinical trials suggest that MBI could be a very effective screening tool in the dense breast population (up to 40% of American and European women; more than 50% of Asian women). A breast lesion phantom has been developed for characterization of MBI system performance. Research Support National Cancer Institute grants CA128407 and CA143716, the Mayo Foundation, and the Susan G. Komen Foundation

The need to understand the behavior of individual stem cells at the various stages of their differentiation and to assess the resulting reparative action in pre-clinical model systems, which typically involves laboratory animals, provides the motivation for imaging of stem cells in vivo at high resolution. Our initial focus is to image cells and cellular events at single cell resolution in vivo in shallow tissues (few mm of intervening tissue) in laboratory mice and rates. In order to accomplish this goal we are building a SPECT-based microscope. We based our design on earlier theoretical work with near-field coded apertures and have adjusted the components of the system to meet the real-world demands of instrument construction and of animal imaging. Our instrumental design possesses a reasonable trade-off between field-of-view, sensitivity, and contrast performance (photon penetration). A layered gold aperture containing 100 pinholes and intended for use in coded aperture imaging application has been designed and constructed. A silicon detector connected to a TimePix readout from the CERN collaborative group was selected for use in our prototype microscope because of its ultra-high spatial and energy resolution capabilities. The combination of the source, aperture, and detector has been modeled and the coded aperture reconstruction of simulated sources is presented in this work.

In this study, we investigated the in vivo application of an integrated small-animal magnetic resonance (MR) and gamma-ray imaging system that consists of a semiconductor-based radiation detector, a parallel-hole collimator, and a specialized radiofrequency coil. Gadodiamide and (99m)Tc sestimibi agents were injected simultaneously into a mouse, and simultaneous dynamic contrast-enhanced MR and scintigraphic images of the kidneys were acquired. The time curves of both the MR signal intensity and radioactivity indicate a rapid uptake of the agents followed by a more gradual excretion, consistent with the previously reported literature. Our results demonstrate the feasibility of measuring multiple biological processes at the same time using both MR contrast agents and radiotracers.

Poster: ECR 2011 / C-1898 / Low-Dose Molecular Breast Imaging for Women with Radiographically Dense Breast Tissue by: D. J. Wagenaar1, J. W. Hugg1, R. A. Moats2, S. Chowdhury1, B. E. Patt1; 1Northridge, CA/US, 2Los Angeles, CA/US

The objective of the study was to demonstrate that more than two types of materials can be effectively separated with x-ray CT using a recently developed energy resolved photon-counting detector. We performed simulations and physical experiments using an energy resolved photon-counting detector with six energy thresholds. For comparison, dual-kVp CT with an integrating detector was also simulated. Iodine- and gadolinium-based contrast agents, as well as several soft-tissue- and bone-like materials were imaged. We plotted the attenuation coefficients for the various materials in a scatter plot for pairs of energy windows. In both simulations and physical experiments, the contrast agents were easily separable from other non-contrast-agent materials in the scatter plot between two properly chosen energy windows. This separation was due to discontinuities in the attenuation coefficient around their unique K-edges. The availability of more than two energy thresholds in a photon-counting detector allowed the separation with one or more contrast agents present. Compared with dual-kVp methods, CT with an energy resolved photon-counting detector provided a larger separation and the freedom to use different energy window pairs to specify the desired target material. We concluded that an energy resolved photon-counting detector with more than two thresholds allowed the separation of more than two types of materials, e.g., soft-tissue-like, bone-like, and one or more materials with K-edges in the energy range of interest. They provided advantages over dual-kVp CT in terms of the degree of separation and the number of materials that can be separated simultaneously.

We describe a continuing design and development of MR-compatible SPECT systems for simultaneous SPECT-MR imaging of small animals. A first generation prototype SPECT system was designed and constructed to fit inside a MRI system with a gradient bore inner diameter of 12 cm. It consists of 3 angularly offset rings of 8 detectors (1"x1", 16x16 pixels MR-compatible solid-state CZT). A matching 24-pinhole collimator sleeve, made of a tungsten-compound, provides projections from a common FOV of ~25 mm. A birdcage RF coil for MRI data acquisition surrounds the collimator. The SPECT system was tested inside a clinical 3T MRI system. Minimal interference was observed on the simultaneously acquired SPECT and MR images. We developed a sparse-view image reconstruction method based on accurate modeling of the point response function (PRF) of each of the 24 pinholes to provide artifact-free SPECT images. The stationary SPECT system provides relatively low resolution of 3-5 mm but high geometric efficiency of 0.5- 1.2% for fast dynamic acquisition, demonstrated in a SPECT renal kinetics study using Tc-99m DTPA. Based on these results, a second generation prototype MR-compatible SPECT system with an outer diameter of 20 cm that fits inside a mid-sized preclinical MRI system is being developed. It consists of 5 rings of 19 CZT detectors. The larger ring diameter allows the use of optimized multi-pinhole collimator designs, such as high system resolution up to ~1 mm, high geometric efficiency, or lower system resolution without collimator rotation. The anticipated performance of the new system is supported by simulation data.

Radiolabeled cells have been imaged for decades in the field of autoradiography. Recent advances in detector and microelectronics technologies have enabled the new field of "digital autoradiography" which remains limited to ex vivo specimens of thin tissue slices. The 3D field-of-view (FOV) of single cell imaging can be extended to millimeters if the low energy (10-30 keV) photon emissions of radionuclides are used for single-photon nuclear imaging. This new microscope uses a coded aperture foil made of highly attenuating elements such as gold or platinum to form the image as a kind of "lens". The detectors used for single-photon emission microscopy are typically silicon detectors with a pixel pitch less than 60 μm. The goal of this work is to image radiolabeled mesenchymal stem cells in vivo in an animal model of tendon repair processes. Single-photon nuclear imaging is an attractive modality for translational medicine since the labeled cells can be imaged simultaneously with the reparative processes by using the dual-isotope imaging technique. The details our microscope's two-layer gold aperture and the operation of the energy-dispersive, pixellated silicon detector are presented along with the first demonstration of energy discrimination with a 57Co source. Cell labeling techniques have been augmented by genetic engineering with the sodium-iodide symporter, a type of reporter gene imaging method that enables in vivo uptake of free 99mTc or an iodine isotope at a time point days or weeks after the insertion of the genetically modified stem cells into the animal model. This microscopy work in animal research may expand to the imaging of reporter-enabled stem cells simultaneously with the expected biological repair process in human clinical trials of stem cell therapies.

Purpose MRI and single-photon emission computed tomography (SPECT) provide complimentary information which could aid in the diagnosis of various diseases. However, acquiring images from both modalities can been problematic. Until recently, SPECT systems could not be integrated with MRI systems due to the use of photomultiplier tubes which do not function in high magnetic fields. The development of semiconductor-based nuclear radiation detectors now allow for the operation of SPECT components within high magnetic fields. We have successfully operated such a SPECT system placed within the bore of a whole-body 4 T MRI system [1]. For a small-bore MRI system, a SPECT system could be placed immediately adjacent and co-axial to the magnet for efficient sequential imaging. Previously constructed ‘back-to-back’ systems were limited to MRI field strengths of only 0.1 T [2,3]. In this study, we present an integration of 7 T MRI and SPECT systems for small-animal imaging.

Despite its high sensitivity, the variable specificity of magnetic resonance imaging (MRI) in breast cancer diagnosis can lead to unnecessary biopsies and over-treatment. Scintimammography (SMM) could potentially supplement MRI to improve the diagnostic specificity. The synergistic combination of MRI and SMM (MRSMM) could result in both high sensitivity from MRI and high specificity from SMM. Development of such a dual-modality system requires the integration of a radio frequency (RF) coil and radiation detector in a strong magnetic field without significant mutual interference. In this study, we developed and tested a unilateral breast array coil specialized for MRSMM imaging. The electromagnetic field, specific absorption ratio and RF coil parameters with cadmium-zinc-telluride detectors encapsulated in specialized RF and gamma-ray shielding mounted within the RF coil were investigated through simulation and experimental measurements. Simultaneous MR and SMM images of a breast phantom were also acquired using the integrated MRSMM system. This work, we feel, represents an important step toward the fabrication of a working MRSMM system.

Molecular Breast Imaging (MBI) is the imaging of radiolabeled drugs, cells, or nanoparticles for breast cancer detection, diagnosis, and treatment. Screening of broad populations of women for breast cancer with mammography has been augmented by the emergence of breast MRI in screening of women at high risk for breast cancer. Screening MBI may benefit the sub-population of women with dense breast tissue that obscures small tumors in mammography. Dedicated breast imaging equipment is necessary to enable detection of early-stage tumors less than 1 cm in size. Recent progress in the development of these instruments is reviewed. Pixellated CZT for single photon MBI imaging of Tc-99m-sestamibi gives high detection sensitivity for early-stage tumors. The use of registered collimators in a near-field geometry gives significantly higher detection efficiency - a factor of 3.6 -, which translates into an equivalent dose reduction factor given the same acquisition time. The radiation dose in the current MBI procedure has been reduced to the level of a four-view digital mammography study. In addition to screening of selected sub-populations, reduced MBI dose allows for dual-isotope, treatment planning, and repeated therapy assessment studies in the era of molecular medicine guided by quantitative molecular imaging.

The goal of this paper was to investigate the benefits that could be realistically achieved on a microCT imaging system with an energy-resolved photon-counting x-ray detector. To this end, we built and evaluated a prototype microCT system based on such a detector. The detector is based on cadmium telluride (CdTe) radiation sensors and application-specific integrated circuit (ASIC) readouts. Each detector pixel can simultaneously count x-ray photons above six energy thresholds, providing the capability for energy-selective x-ray imaging. We tested the spectroscopic performance of the system using polychromatic x-ray radiation and various filtering materials with K-absorption edges. Tomographic images were then acquired of a cylindrical PMMA phantom containing holes filled with various materials. Results were also compared with those acquired using an intensity-integrating x-ray detector and single-energy (i.e. non-energy-selective) CT. This paper describes the functionality and performance of the system, and presents preliminary spectroscopic and tomographic results. The spectroscopic experiments showed that the energy-resolved photon-counting detector was capable of measuring energy spectra from polychromatic sources like a standard x-ray tube, and resolving absorption edges present in the energy range used for imaging. However, the spectral quality was degraded by spectral distortions resulting from degrading factors, including finite energy resolution and charge sharing. We developed a simple charge-sharing model to reproduce these distortions. The tomographic experiments showed that the availability of multiple energy thresholds in the photon-counting detector allowed us to simultaneously measure target-to-background contrasts in different energy ranges. Compared with single-energy CT with an integrating detector, this feature was especially useful to improve differentiation of materials with different attenuation coefficient energy dependences.

Conventional x-ray detectors integrate the photon energy flux, losing individual photon energy information. By contrast, energy resolved photon-counting x-ray detectors (PCXDs) count photons in energy windows, thus retaining some energy information. This provides a number of advantages, including the use of energy information to aid in material discrimination. However, this capability relies on accurately measuring changes in the energy spectrum as the x-ray beam passes through the object. Several effects, including characteristic x-ray effects and charge sharing between detector pixels, result in distortions in the energy spectrum that complicate measuring the attenuating effects of the object on the energy spectrum. Our goal was to investigate and develop models for these effects that would be useful in compensating for them in applications involving spectral analysis. We used a previously developed 6-threshold CdTe-based PCXD to validate the models. Previously with this detector we observed higher than predicted counts at low energies. Characteristic x-rays emitted in the detector can distort the spectrum in a pixel via x-ray escape either out of the detector or into adjacent pixels, giving rise to a count with a reduced energy. The escaped x-rays can also produce reduced-energy counts in adjacent pixels. The second effect, charge sharing, results since x-ray interactions in the detector produce a charge cloud with finite size. If close to a pixel boundary and combined with charge diffusion, reduced-energy counts in both pixels can be produced. In this study, we developed a fast Monte Carlo method for modeling characteristic x-ray effects and an analytic method for modeling charge sharing effects. The models produced energy spectra in good agreement with those measured by the PCXD. These models can be used to improve the performance of energy-based composition estimation and ring correction methods by modeling the spectral distortions present in real detectors.

We have developed an application specific integrated circuit (ASIC) suitable for the readout of up to 64 silicon photomultipliers (SiPM) or multi-pixel photon counters (MPPCs). The ASIC can be used with SiPMs/MPPCs and scintillators for energy spectroscopy and timing of ionizing radiation and provides important functionality for SiPMs: The preamplifier input potential can be programmed to adjust the bias voltage for the SiPMs connected to the input. The input charge range is relatively large (−20 pC to 55 pC) and the input noise can be as low as 1 fC. The ASIC triggers, if one of the input signals exceeds the threshold voltage, and the signal amplitude can be sampled. For all readout channels the ASIC delivers the signal amplitude, i.e., photon energy, and the time between the trigger and the sample. The ASIC has a programmable register to configure digital-to-analog converters for the preamplifier input potentials, the trigger thresholds, the internal bias setting and other functionality. Many ASICs can be combined for the readout of multiple arrays of SiPMs/MPPCs. The preamplifier input is designed for capacitive load of up to 300 pF and a dark current of up to 10 μA. We have produced and tested the ASIC connected to MPPCs and LYSO scintillators. The article describes the functionality of the ASIC and shows energy spectra measured with radioactive sources.