Kisung Lee

Performance Comparisons of Continuous Miniature Crystal Element (cMiCE) Detectors

In this paper, we investigated the performance characteristics of continuous miniature crystal element (cMiCE) detectors. Versions with a 25 mm by 25 mm by 4 mm-thick LSO crystal and with a 50 mm by 50 mm by 8 mm-thick LYSO crystal were evaluated. Both detectors utilize a 64-channel flat panel photomultiplier tube (PMT). The intrinsic spatial resolution for the detectors was evaluated using Anger (i.e., simple centroid) positioning and a statistics based positioning (SBP) algorithm. We also compared the intrinsic spatial resolution for the 8-mm-thick LYSO crystal using different reflective materials (e.g., TFE Teflon, white paint, and a polymer mirror film) applied on the entrance surface of the crystal. The average energy resolution was 20% for the 4-mm-thick LSO crystal and ranged from 16% to 21%, depending upon reflective material, for the 8-mm-thick LYSO crystal. The average intrinsic spatial resolution for the 4-mm-thick crystal was 1.8-mm full width at half maximum (FWHM) for Anger positioning to within 3 mm of the crystals edge and 1.14-mm FWHM for SBP to within 2 mm of the edge. The average intrinsic spatial resolution for the 8-mm-thick crystal was 2.2-mm FWHM for Anger positioning to within 8 mm of the crystals edge and 1.3- to 1.5-mm FWHM (depending on reflective material used) for SBP to within 2 mm of the edge. Intrinsic spatial resolution is reported without correcting for point source size. The point spot flux had a FWHM of about 0.52 mm. The SBP algorithm resulted in significant improvement in intrinsic spatial resolution, linearity of positioning result, and effective field of view (FOV) for our cMiCE detector

Pragmatic fully 3D image reconstruction for the MiCES mouse imaging PET scanner

We present a pragmatic approach to image reconstruction for data from the micro crystal elements system (MiCES) fully 3D mouse imaging positron emission tomography (PET) scanner under construction at the University of Washington. Our approach is modelled on fully 3D image reconstruction used in clinical PET scanners, which is based on Fourier rebinning (FORE) followed by 2D iterative image reconstruction using ordered-subsets expectation-maximization (OSEM). The use of iterative methods allows modelling of physical effects (e.g., statistical noise, detector blurring, attenuation, etc), while FORE accelerates the reconstruction process by reducing the fully 3D data to a stacked set of independent 2D sinograms. Previous investigations have indicated that non-stationary detector point-spread response effects, which are typically ignored for clinical imaging, significantly impact image quality for the MiCES scanner geometry. To model the effect of non-stationary detector blurring (DB) in the FORE+OSEM(DB) algorithm, we have added a factorized system matrix to the ASPIRE reconstruction library. Initial results indicate that the proposed approach produces an improvement in resolution without an undue increase in noise and without a significant increase in the computational burden. The impact on task performance, however, remains to be evaluated.

Inhibition of lipopolysaccharide-induced nitric oxide synthesis by nicotine through S6K1-p42/44 MAPK pathway and STAT3 (Ser 727) phosphorylation in Raw 264.7 cells.

Lipopolysaccharide (LPS) has been known to produce inflammatory modulators such as tumor necrosis factor alpha (TNF-alpha) or nitric oxide (NO). In this study, we examined the effects of nicotine on LPS enhanced NO synthesis and inducible nitric oxide synthase (iNOS) expression in macrophages. LPS-induced NO synthesis and iNOS expression were significantly decreased by nicotine. To investigate the signaling mechanism of nicotine induced suppression of NO synthesis and iNOS expression induced by LPS, we focused on the possible roles of p42/44 MAPK, S6K1, and signal transducers and activators of transcription 3 (STAT3) signaling. LPS is known to activate p42/44 MAPK and S6K1, which in turn activates STAT3 to induce inflammatory regulators. Pretreatment of cells with nicotine blocked LPS-induced p42/44 MAPK and S6K1 as well as iNOS promoter activity. Furthermore, we found that LPS-induced phosphorylation of STAT3 at serine 727 is mediated by S6K1-p42/44 MAPK pathway, and this STAT3 phosphorylation was also blocked by nicotine. We also found that downregulation of STAT3 using STAT3 siRNA resulted in suppression of the NO synthesis and iNOS expression. Taken together, our results suggest that nicotine inhibits LPS-induced NO synthesis through suppression of S6K1-p42/44 MAPK pathway and phosphorylation of STAT3 in Raw 264.7 cells.

Impact of system design parameters on image figures of merit for a mouse PET scanner

In this study, an analytical simulation model was developed to investigate how system design parameters affect image figures of merit and task performance for small animal positron emission tomography (PET) scanners designed to image mice. For a very high resolution imaging system, important physical effects that may impact image quality are positron range, annihilation photon acollinearity, detector point-spread function (PSF) and coincident photon count levels (i.e., statistical noise). Modeling of these effects was included in an analytical simulation that generated multiple realizations of sinograms with varying levels of each effect. To evaluate image quality with respect to quantitation and detection task performance, four different figures of merit were measured: 1) root mean square error (RMSE); 2) a region of interest SNR (SNR/sub ROI/); 3) nonprewhitening matched filter SNR (SNR/sub NPW/); and 4) recovery coefficient. The results indicate that for very high resolution imaging systems, the increase in positron range of C-11 compared to F-18 radiolabeling causes a significant reduction of quantitation (SNR/sub ROI/) and detection (SNR/sub NPW/) accuracy for small regions. In addition, changing the shape of the detector PSF, which depends on crystal thickness, causes significant variations in quantitation and detection performance. However, while increasing noise levels significantly increase RMSE and decrease detectability (SNR/sub NPW/), the quantitation task performance (SNR/sub ROI/), is less sensitive to noise levels. These results imply that resolution is more important than sensitivity for quantitation task performance, while sensitivity is a more significant issue for detection. The analytical simulation model can be used for estimating task performance of small animal PET systems more rapidly than existing full Monte Carlo methods, although Monte Carlo methods are needed to estimate system parameters.

Comparison of operator radiation exposure between C-arm and O-arm fluoroscopy for orthopaedic surgery

The O-arm system has recently been introduced and has the capability of combined two-dimensional (2-D) fluoroscopy imaging and three-dimensional computed tomography imaging. In this study, an orthopaedic surgical procedure using C-arm and O-arm systems in their 2-D fluoroscopy modes was simulated and the radiation doses to susceptible organs to which operators can be exposed were investigated. The experiments were performed in four configurations of the location of the X-ray source and detector. Shielding effects on the thyroid surface and the direct exposure delivered to the surgeons hands were also compared. The results obtained show that the O-arm delivered higher doses to the sensitive organs of the operator in all configurations. The thyroid shield cut-off 89 % of the dose in the posteroanterior configuration of both imaging systems. Thus, the operators need to pay more attention to managing radiation exposure, especially when using the O-arm system.

Role of Phospholipase D2 in Anti-Apoptotic Signaling Through Increased Expressions of Bcl-2 and Bcl-xL

We have previously reported that Fas‐resistant A20 cells (FasR) have phospholipase D (PLD) activity upregulated by endogenous PLD2 overexpression. In the present study, we investigated how overexpressed PLD2 in FasR could generate survival signals by regulating the protein levels of anti‐apoptotic Bcl‐2 and Bcl‐xL. To confirm the effect of PLD2 on Bcl‐2 protein levels, we transfected PLD2 into wild‐type murine B lymphoma A20 cells. The transfected cells showed markedly the increases in Bcl‐2 and Bcl‐xL protein levels, and became resistant to Fas‐induced apoptosis, similar to FasR. Treatment of wild‐type A20 cells with phosphatidic acid (PA), the metabolic end product of PLD2 derived from phosphatidylcholin, markedly increased levels of anti‐apoptotic Bcl‐2 and Bcl‐xL proteins. Moreover, PA‐induced expressions of Bcl‐2 and Bcl‐xL were enhanced by propranolol, an inhibitor of PA phospholydrolase (PAP), whereas completely blocked by mepacrine, an inhibitor of phospholipase A2 (PLA2), suggesting that PLA2 metabolite of PA is responsible for the increases in Bcl‐2 and Bcl‐xL protein levels. We further confirmed the involvement of arachidonic acid (AA) in PA‐induced survival signals by showing that 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphate (DPPA), PA without AA, was unable to increase Bcl‐2 and Bcl‐xL proteins. Moreover, PA notably increased cyclooxygenase (COX)‐2 protein expression, and PA‐induced expression of both Bcl‐2 and Bcl‐xL was inhibited by NS‐398, a specific inhibitor of COX‐2. Taken together, these findings demonstrate that PA generated by PLD2 plays an important role in cell survival during Fas‐mediated apoptosis through the increased Bcl‐2 and Bcl‐xL protein levels which resulted from PLA2 and AA‐COX2 pathway. J. Cell. Biochem. 101: 1409–1422, 2007.

Overexpression of phospholipase D suppresses taxotere-induced cell death in stomach cancer cells

Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to generate phosphatidic acid (PA) and choline. There are at least two PLD isozymes, PLD1 and PLD2. Genetic and pharmacological approaches implicate both PLD isozymes in a diverse range of cellular processes, including receptor signaling, membrane transport control, and actin cytoskeleton reorganization. Several recent studies reported that PLD has a role in signaling pathways that oppose apoptosis and promote cell survival in cancer. In this study, we examined the role of PLD in taxotere-induced apoptosis in stomach cell lines; normal stomach (NSC) and stomach cancer cells (SNU 484). Taxotere treatment resulted in increase of PLD activity. To confirm the role of PLD in taxotere-induced apoptosis, PLDs were transfected into SNU 484 cells. Overexpression of PLD isozymes resulted in inhibition of taxotere-induced apoptotic cell death, evidenced by decreased degradation of chromosomal DNA, and increased cell viability. Concurrently, Bcl-2 expression was upregulated, and taxotere-induced activation of procaspase 3 was inhibited after PLDs transfection. However, when PLD was selectively inhibited by specific siRNA-PLD1 or -PLD2, taxotere-induced apoptosis was exacerbated in SNU 484 cells. On top of this, PA -- the product of PLDs, also resulted in upregulation of Bcl-2 in SNU 484. Although PA-induced Bcl-2 expression was blocked by mepacrine, an inhibitor of phospholipase A(2) (PLA(2)), increased Bcl-2 expression by PA was not abrogated by propranolol, an inhibitor of PA phospholyhydrolase (PAP). Taken together, PLD1 and PLD2 are closely related with Bcl-2 expression together with PLA(2), but not with PAP, during taxotere-induced apoptosis in SNU 484 cells.

Development of a Single Detector Ring Micro Crystal Element Scanner: QuickPET II

This article describes a single ring version of the micro crystal element scanner (MiCES) and investigation of its spatial resolution imaging characteristics for mouse positron emission tomography (PET) imaging. This single ring version of the MiCES system, referred to as QuickPET II, consists of 18 MiCE detector modules mounted as a single ring in a vertical gantry. The system has a 5.76-cm transverse field of view and a 1.98-cm axial field of view. In addition to the scanner and data acquisition system, we have developed an iterative reconstruction that includes a model of the systems detector response function. Evaluation images of line sources and mice have been acquired. Using filtered backprojection, the resolution for a reconstructed line source has been measured at 1.2 mm full width at half maximum. F-18-2-fluoro-2-deoxyglucose mouse PET images are provided. The result shows that QuickPET II has the imaging characteristics to support high-resolution, static mouse PET studies using 18-F labeled compounds.

Methods to Detect Road Features for Video-Based In-Vehicle Navigation Systems

Understanding road features such as position and color of lane markings in a live video captured from a moving vehicle is essential in building video-based car navigation systems. In this article, the authors present a framework to detect road features in 2 difficult situations: (a) ambiguous road surface conditions (i.e., damaged roads and occluded lane markings caused by the presence of other vehicles on the road) and (b) poor illumination conditions (e.g., backlight, during sunset). Furthermore, to understand the lane number that a driver is driving on, the authors present a Bayesian network (BN) model, which is necessary to support more sophisticated navigation services for drivers such as recommending lane change at an appropriate time before turning left or right at the next intersection. In the proposed BN approach, evidence from (1) a computer vision engine (e.g., lane-color detection) and (2) a navigation database (e.g., the total number of lanes) was fused to more accurately decide the lane number. Extensive simulation results indicated that the proposed methods are both robust and effective in detecting road features for a video-based car navigation system.

Phospholipase D1 activation through Src and Ras is involved in basic fibroblast growth factor‐induced neurite outgrowth of H19‐7 cells

Phospholipase D (PLD) is implicated in a variety of physiological processes that reveal it to be a member of the signal transducing phospholipases. We found that PLD1 is activated when basic fibroblast growth factor (bFGF) stimulates neurite outgrowth of an immortalized hippocampal cell line (H19‐7). Overexpression of PLD1 in H19‐7 cells dramatically elongated bFGF‐induced neurite outgrowth and increased PLD activity. Transfection of DN‐rPLD1 blocked bFGF‐induced PLD activation and completely inhibited neurite outgrowth induced by bFGF, suggesting that PLD1 activation is important in bFGF‐induced neurite outgrowth of H19‐7 cells. PLD activation and neurite outgrowth induced by bFGF was dependent on phospholipase C gamma (PLC‐γ) and Ca2+, but not protein kinase C (PKC). Furthermore, inhibition of Src and Ras partially blocked bFGF‐induced PLD activation and neurite outgrowth, respectively. Coinhibition of Src and Ras completely blocked bFGF‐induced PLD activation, suggesting that Src and Ras independently regulate PLD1 activation. Interestingly, bFGF‐induced PLD activation and neurite outgrowth did not require ERK1/2 activated by Ras. Taken together, this study demonstrates that bFGF activates PLD1 through PLC‐γ activation, which leads to neurite outgrowth in H19‐7 cells. Furthermore, our results show that PLD1 activation by bFGF is regulated by Src and Ras independently. J. Cell. Biochem. 101: 221–234, 2007.