A switch in the control of growth of the wing imaginal disks of Manduca sexta.

BACKGROUND: Insulin and ecdysone are the key extrinsic regulators of growth for the wing imaginal disks of insects. In vitro tissue culture studies have shown that these two growth regulators act synergistically: either factor alone stimulates only limited growth, but together they stimulate disks to grow at a rate identical to that observed in situ. It is generally thought that insulin signaling links growth to nutrition, and that starvation stops growth because it inhibits insulin secretion. At the end of larval life feeding stops but the disks continue to grow, so at that time disk growth has become uncoupled from nutrition. We sought to determine at exactly what point in development this uncoupling occurs. METHODOLOGY: Growth and cell proliferation in the wing imaginal disks and hemolymph carbohydrate concentrations were measured at various stages in the last larval instar under experimental conditions of starvation, ligation, rescue, and hormone treatment. PRINCIPAL FINDINGS: Here we show that in the last larval instar of M. sexta, the uncoupling of nutrition and growth occurs as the larva passes the critical weight. Before this time, starvation causes a decline in hemolymph glucose and trehalose and a cessation of wing imaginal disks growth, which can be rescued by injections of trehalose. After the critical weight the trehalose response to starvation disappears, and the expression of insulin becomes decoupled from nutrition. After the critical weight the wing disks loose their sensitivity to repression by juvenile hormone, and factors from the abdomen, but not the brain, are required to drive continued growth. CONCLUSIONS: During the last larval instar imaginal disk growth becomes decoupled from somatic growth at the time that the endocrine events of metamorphosis are initiated. These regulatory changes ensure that disk growth continues uninterrupted when the nutritive and endocrine signals undergo the drastic changes associated with metamorphosis.

POCS-based reconstruction of multiplexed sensitivity encoded MRI (POCSMUSE): A general algorithm for reducing motion-related artifacts.

PURPOSE: A projection onto convex sets reconstruction of multiplexed sensitivity encoded MRI (POCSMUSE) is developed to reduce motion-related artifacts, including respiration artifacts in abdominal imaging and aliasing artifacts in interleaved diffusion-weighted imaging. THEORY: Images with reduced artifacts are reconstructed with an iterative projection onto convex sets (POCS) procedure that uses the coil sensitivity profile as a constraint. This method can be applied to data obtained with different pulse sequences and k-space trajectories. In addition, various constraints can be incorporated to stabilize the reconstruction of ill-conditioned matrices. METHODS: The POCSMUSE technique was applied to abdominal fast spin-echo imaging data, and its effectiveness in respiratory-triggered scans was evaluated. The POCSMUSE method was also applied to reduce aliasing artifacts due to shot-to-shot phase variations in interleaved diffusion-weighted imaging data corresponding to different k-space trajectories and matrix condition numbers. RESULTS: Experimental results show that the POCSMUSE technique can effectively reduce motion-related artifacts in data obtained with different pulse sequences, k-space trajectories and contrasts. CONCLUSION: POCSMUSE is a general post-processing algorithm for reduction of motion-related artifacts. It is compatible with different pulse sequences, and can also be used to further reduce residual artifacts in data produced by existing motion artifact reduction methods.

A model of sequential heart and composite tissue allotransplant in rats.

BACKGROUND: Some of the 600,000 patients with solid organ allotransplants need reconstruction with a composite tissue allotransplant, such as the hand, abdominal wall, or face. The aim of this study was to develop a rat model for assessing the effects of a secondary composite tissue allotransplant on a primary heart allotransplant. METHODS: Hearts of Wistar Kyoto rats were harvested and transplanted heterotopically to the neck of recipient Fisher 344 rats. The anastomoses were performed between the donor brachiocephalic artery and the recipient left common carotid artery, and between the donor pulmonary artery and the recipient external jugular vein. Recipients received cyclosporine A for 10 days only. Heart rate was assessed noninvasively. The sequential composite tissue allotransplant consisted of a 3 x 3-cm abdominal musculocutaneous flap harvested from Lewis rats and transplanted to the abdomen of the heart allotransplant recipients. The abdominal flap vessels were connected to the femoral vessels. No further immunosuppression was administered following the composite tissue allotransplant. Ten days after composite tissue allotransplantation, rejection of the heart and abdominal flap was assessed histologically. RESULTS: The rat survival rate of the two-stage transplant surgery was 80 percent. The transplanted heart rate decreased from 150 +/- 22 beats per minute immediately after transplant to 83 +/- 12 beats per minute on day 20 (10 days after stopping immunosuppression). CONCLUSIONS: This sequential allotransplant model is technically demanding. It will facilitate investigation of the effects of a secondary composite tissue allotransplant following primary solid organ transplantation and could be useful in developing future immunotherapeutic strategies.

Development and Optimization of Four-dimensional Magnetic Resonance Imaging (4D-MRI) for Radiation Therapy

A tenet of modern radiotherapy (RT) is to identify the treatment target accurately, following which the high-dose treatment volume may be expanded into the surrounding tissues in order to create the clinical and planning target volumes. Respiratory motion can induce errors in target volume delineation and dose delivery in radiation therapy for thoracic and abdominal cancers. Historically, radiotherapy treatment planning in the thoracic and abdominal regions has used 2D or 3D images acquired under uncoached free-breathing conditions, irrespective of whether the target tumor is moving or not. Once the gross target volume has been delineated, standard margins are commonly added in order to account for motion. However, the generic margins do not usually take the target motion trajectory into consideration. That may lead to under- or over-estimate motion with subsequent risk of missing the target during treatment or irradiating excessive normal tissue. That introduces systematic errors into treatment planning and delivery. In clinical practice, four-dimensional (4D) imaging has been popular in For RT motion management. It provides temporal information about tumor and organ at risk motion, and it permits patient-specific treatment planning. The most common contemporary imaging technique for identifying tumor motion is 4D computed tomography (4D-CT). However, CT has poor soft tissue contrast and it induce ionizing radiation hazard. In the last decade, 4D magnetic resonance imaging (4D-MRI) has become an emerging tool to image respiratory motion, especially in the abdomen, because of the superior soft-tissue contrast. Recently, several 4D-MRI techniques have been proposed, including prospective and retrospective approaches. Nevertheless, 4D-MRI techniques are faced with several challenges: 1) suboptimal and inconsistent tumor contrast with large inter-patient variation; 2) relatively low temporal-spatial resolution; 3) it lacks a reliable respiratory surrogate. In this research work, novel 4D-MRI techniques applying MRI weightings that was not used in existing 4D-MRI techniques, including T2/T1-weighted, T2-weighted and Diffusion-weighted MRI were investigated. A result-driven phase retrospective sorting method was proposed, and it was applied to image space as well as k-space of MR imaging. Novel image-based respiratory surrogates were developed, improved and evaluated.

Numerical Simulations for the Design of Novel Integrated Parallel Reception, Excitation, and Shimming (iPRES) Coil Arrays

Magnetic field inhomogeneity results in image artifacts including signal loss, image blurring and distortions, leading to decreased diagnostic accuracy. Conventional multi-coil (MC) shimming method employs both RF coils and shimming coils, whose mutual interference induces a tradeoff between RF signal-to-noise (SNR) ratio and shimming performance. To address this issue, RF coils were integrated with direct-current (DC) shim coils to shim field inhomogeneity while concurrently emitting and receiving RF signal without being blocked by the shim coils. The currents applied to the new coils, termed iPRES (integrated parallel reception, excitation and shimming), were optimized in the numerical simulation to improve the shimming performance. The objectives of this work is to offer a guideline for designing the optimal iPRES coil arrays to shim the abdomen.

In this thesis work, the main field () inhomogeneity was evaluated by root mean square error (RMSE). To investigate the shimming abilities of iPRES coil arrays, a set of the human abdomen MRI data was collected for the numerical simulations. Thereafter, different simplified iPRES(N) coil arrays were numerically modeled, including a 1-channel iPRES coil and 8-channel iPRES coil arrays. For 8-channel iPRES coil arrays, each RF coil was split into smaller DC loops in the x, y and z direction to provide extra shimming freedom. Additionally, the number of DC loops in a RF coil was increased from 1 to 5 to find the optimal divisions in z direction. Furthermore, switches were numerically implemented into iPRES coils to reduce the number of power supplies while still providing similar shimming performance with equivalent iPRES coil arrays.

The optimizations demonstrate that the shimming ability of an iPRES coil array increases with number of DC loops per RF coil. Furthermore, the z direction divisions tend to be more effective in reducing field inhomogeneity than the x and y divisions. Moreover, the shimming performance of an iPRES coil array gradually reach to a saturation level when the number of DC loops per RF coil is large enough. Finally, when switches were numerically implemented in the iPRES(4) coil array, the number of power supplies can be reduced from 32 to 8 while keeping the shimming performance similar to iPRES(3) and better than iPRES(1). This thesis work offers a guidance for the designs of iPRES coil arrays.

Effective Dose Estimation in Fast-kV Switch Dual Energy Computed Tomography

Purpose

The objective of our study was to test a new approach to approximating organ dose by using the effective energy of the combined 80kV/140kV beam used in fast kV switch dual-energy (DE) computed tomography (CT). The two primary focuses of the study were to first validate experimentally the dose equivalency between MOSFET and ion chamber (as a gold standard) in a fast kV switch DE environment, and secondly to estimate effective dose (ED) of DECT scans using MOSFET detectors and an anthropomorphic phantom.

Materials and Methods

A GE Discovery 750 CT scanner was employed using a fast-kV switch abdomen/pelvis protocol alternating between 80 kV and 140 kV. The specific aims of our study were to (1) Characterize the effective energy of the dual energy environment; (2) Estimate the f-factor for soft tissue; (3) Calibrate the MOSFET detectors using a beam with effective energy equal to the combined DE environment; (4) Validate our calibration by using MOSFET detectors and ion chamber to measure dose at the center of a CTDI body phantom; (5) Measure ED for an abdomen/pelvis scan using an anthropomorphic phantom and applying ICRP 103 tissue weighting factors; and (6) Estimate ED using AAPM Dose Length Product (DLP) method. The effective energy of the combined beam was calculated by measuring dose with an ion chamber under varying thicknesses of aluminum to determine half-value layer (HVL).

Results

The effective energy of the combined dual-energy beams was found to be 42.8 kV. After calibration, tissue dose in the center of the CTDI body phantom was measured at 1.71 ± 0.01 cGy using an ion chamber, and 1.73±0.04 and 1.69±0.09 using two separate MOSFET detectors. This result showed a -0.93% and 1.40 % difference, respectively, between ion chamber and MOSFET. ED from the dual-energy scan was calculated as 16.49 ± 0.04 mSv by the MOSFET method and 14.62 mSv by the DLP method.