Feasibility study of a new RF coil design for prostate MRI.

The combined use of a torso-pelvic RF array coil and endorectal RF coil is the current state-of-the-art in prostate MRI. The endorectal coil provides high detection sensitivity to acquire high-spatial resolution images and spectroscopic data, while the torso-pelvic coil provides large coverage to assess pelvic lymph nodes and pelvic bones for metastatic disease. However, the use of an endorectal coil is an invasive procedure that presents difficulties for both patients and technicians. In this study, we propose a novel non-invasive RF coil design that can provide both image signal to noise ratio and field of view coverage comparable to the combined torso-pelvic and endorectal coil configuration. A prototype coil was constructed and tested using a pelvic phantom. The results demonstrate that this new design is a viable alternative for prostate MRI.

Feasibility study of a unilateral RF array coil for MR-scintimammography.

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.

Simultaneous in vivo dynamic contrast-enhanced magnetic resonance and scintigraphic imaging.

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.

MR-based keyhole SPECT for small animal imaging.

The rationale for multi-modality imaging is to integrate the strengths of different imaging technologies while reducing the shortcomings of an individual modality. The work presented here proposes a limited-field-of-view (LFOV) SPECT reconstruction technique that can be implemented on a multi-modality MR/SPECT system that can be used to obtain simultaneous MRI and SPECT images for small animal imaging. The reason for using a combined MR/SPECT system in this work is to eliminate any possible misregistration between the two sets of images when MR images are used as a priori information for SPECT. In nuclear imaging the target area is usually smaller than the entire object; thus, focusing the detector on the LFOV results in various advantages including the use of a smaller nuclear detector (less cost), smaller reconstruction region (faster reconstruction) and higher spatial resolution when used in conjunction with pinhole collimators with magnification. The MR/SPECT system can be used to choose a region of interest (ROI) for SPECT. A priori information obtained by the full field-of-view (FOV) MRI combined with the preliminary SPECT image can be used to reduce the dimensions of the SPECT reconstruction by limiting the computation to the smaller FOV while reducing artifacts resulting from the truncated data. Since the technique is based on SPECT imaging within the LFOV it will be called the keyhole SPECT (K-SPECT) method. At first MRI images of the entire object using a larger FOV are obtained to determine the location of the ROI covering the target organ. Once the ROI is determined, the animal is moved inside the radiofrequency (rf) coil to bring the target area inside the LFOV and then simultaneous MRI and SPECT are performed. The spatial resolution of the SPECT image is improved by employing a pinhole collimator with magnification >1 by having carefully calculated acceptance angles for each pinhole to avoid multiplexing. In our design all the pinholes are focused to the center of the LFOV. K-SPECT reconstruction is accomplished by generating an adaptive weighting matrix using a priori information obtained by simultaneously acquired MR images and the radioactivity distribution obtained from the ROI region of the SPECT image that is reconstructed without any a priori input. Preliminary results using simulations with numerical phantoms show that the image resolution of the SPECT image within the LFOV is improved while minimizing artifacts arising from parts of the object outside the LFOV due to the chosen magnification and the new reconstruction technique. The root-mean-square-error (RMSE) in the out-of-field artifacts was reduced by 60% for spherical phantoms using the K-SPECT reconstruction technique and by 48.5-52.6% for the heart in the case with the MOBY phantom. The K-SPECT reconstruction technique significantly improved the spatial resolution and quantification while reducing artifacts from the contributions outside the LFOV as well as reducing the dimension of the reconstruction matrix.

Quantitative fluorescence tomography using a trimodality system: in vivo validation.

A fully integrated trimodality fluorescence, diffuse optical, and x-ray computed tomography (FT/DOT/XCT) system for small animal imaging is reported in this work. The main purpose of this system is to obtain quantitatively accurate fluorescence concentration images using a multimodality approach. XCT offers anatomical information, while DOT provides the necessary background optical property map to improve FT image accuracy. The quantitative accuracy of this trimodality system is demonstrated in vivo. In particular, we show that a 2-mm-diam fluorescence inclusion located 8 mm deep in a nude mouse can only be localized when functional a priori information from DOT is available. However, the error in the recovered fluorophore concentration is nearly 87%. On the other hand, the fluorophore concentration can be accurately recovered within 2% error when both DOT functional and XCT structural a priori information are utilized together to guide and constrain the FT reconstruction algorithm.

Quantitative fluorescence tomography using a combined tri-modality FT/DOT/XCT system.

In this work, a first-of-its-kind fully integrated tri-modality system that combines fluorescence, diffuse optical and x-ray tomography (FT/DOT/XCT) into the same setting is presented. The purpose of this system is to perform quantitative fluorescence tomography using multi-modality imaging approach. XCT anatomical information is used as structural priori while optical background heterogeneity information obtained by DOT measurements is used as functional priori. The performance of the hybrid system is evaluated using multi-modality phantoms. In particular, we show that a 2.4 mm diameter fluorescence inclusion located in a heterogeneous medium can be localized accurately with the functional a priori information, although the fluorophore concentration is recovered with 70% error. On the other hand, the fluorophore concentration can be accurately recovered within 8% error only when both DOT optical background functional and XCT structural a priori information are utilized to guide and constrain the FT reconstruction algorithm.

Development of a new RF coil and gamma-ray radiation shielding assembly for improved MR image quality in SPECT/MRI.

Magnetic resonance (MR)-based multimodality imaging systems, such as single-photon emission tomography (SPECT)/magnetic resonance imaging (MRI) or positron emission tomography (PET)/MRI, face many difficulties because of problems with the compatibility of the nuclear detector system with the MR system. However, several studies have reported on the design considerations of MR-compatible nuclear detectors for combined SPECT/MRI. In this study, we developed a new radiofrequency (RF) coil and gamma-ray radiation shielding assembly to advance the practical implementation of SPECT/MRI in providing high sensitivity while minimizing the interference between the MRI and SPECT systems. The proposed assembly consists of a three-channel receive-only RF coil and gamma-ray radiation shields made of a specialized lead composite powder designed to reduce conductivity and thus minimizing any effect on the magnetic field arising from the induced eddy currents. A conventional birdcage RF coil was also tested for comparison with the proposed RF coil. Quality (Q)-factors were measured using both RF coils without any shielding, with solid lead shielding, and with our composite lead shielding. Signal-to-noise ratios (SNRs) were calculated using 4 T MR images of phantoms both with and without the new gamma-ray radiation shields. The Q-factor and SNR measurements demonstrate the improved MRI performance due to the new RF coil/gamma-ray radiation shield assembly designed for SPECT/MRI, making it a useful addition to multimodality imaging technology not only for animal studies but also for in vivo study of humans.

Development of an MR-compatible SPECT system (MRSPECT) for simultaneous data acquisition.

In medical imaging, single-photon emission computed tomography (SPECT) can provide specific functional information while magnetic resonance imaging (MRI) can provide high spatial resolution anatomical information as well as complementary functional information. In this study, we developed a miniaturized dual-modality SPECT/MRI (MRSPECT) system and demonstrated the feasibility of simultaneous SPECT and MRI data acquisition, with the possibility of whole-body MRSPECT systems through suitable scaling of components. For our MRSPECT system, a cadmium-zinc-telluride (CZT) nuclear radiation detector was interfaced with a specialized radiofrequency (RF) coil and placed within a whole-body 4 T MRI system. Various phantom experiments characterized the interaction between the SPECT and MRI hardware components. The metallic components of the SPECT hardware altered the B(0) field and generated a non-uniform reduction in the signal-to-noise ratio (SNR) of the MR images. The presence of a magnetic field generated a position shift and resolution loss in the nuclear projection data. Various techniques were proposed to compensate for these adverse effects. Overall, our results demonstrate that accurate, simultaneous SPECT and MRI data acquisition is feasible, justifying the further development of MRSPECT for either small-animal imaging or whole-body human systems by using appropriate components.

Initial Investigation of preclinical integrated SPECT and MR imaging.

Single-photon emission computed tomography (SPECT) can provide specific functional information while magnetic resonance imaging (MRI) can provide high-spatial resolution anatomical information as well as complementary functional information. In this study, we utilized a dual modality SPECT/MRI (MRSPECT) system to investigate the integration of SPECT and MRI for improved image accuracy. The MRSPECT system consisted of a cadmium-zinc-telluride (CZT) nuclear radiation detector interfaced with a specialized radiofrequency (RF) coil that was placed within a whole-body 4 T MRI system. The importance of proper corrections for non-uniform detector sensitivity and Lorentz force effects was demonstrated. MRI data were utilized for attenuation correction (AC) of the nuclear projection data and optimized Wiener filtering of the SPECT reconstruction for improved image accuracy. Finally, simultaneous dual-imaging of a nude mouse was performed to demonstrated the utility of co-registration for accurate localization of a radioactive source.

Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases.

Autoreactive memory T lymphocytes are implicated in the pathogenesis of autoimmune diseases. Here we demonstrate that disease-associated autoreactive T cells from patients with type-1 diabetes mellitus or rheumatoid arthritis (RA) are mainly CD4+ CCR7- CD45RA- effector memory T cells (T(EM) cells) with elevated Kv1.3 potassium channel expression. In contrast, T cells with other antigen specificities from these patients, or autoreactive T cells from healthy individuals and disease controls, express low levels of Kv1.3 and are predominantly naïve or central-memory (T(CM)) cells. In T(EM) cells, Kv1.3 traffics to the immunological synapse during antigen presentation where it colocalizes with Kvbeta2, SAP97, ZIP, p56(lck), and CD4. Although Kv1.3 inhibitors [ShK(L5)-amide (SL5) and PAP1] do not prevent immunological synapse formation, they suppress Ca2+-signaling, cytokine production, and proliferation of autoantigen-specific T(EM) cells at pharmacologically relevant concentrations while sparing other classes of T cells. Kv1.3 inhibitors ameliorate pristane-induced arthritis in rats and reduce the incidence of experimental autoimmune diabetes in diabetes-prone (DP-BB/W) rats. Repeated dosing with Kv1.3 inhibitors in rats has not revealed systemic toxicity. Further development of Kv1.3 blockers for autoimmune disease therapy is warranted.