Noquist: reduced field-of-view imaging by direct Fourier inversion.

A novel technique called "Noquist" is introduced for the acceleration of dynamic cardiac magnetic resonance imaging (CMRI). With the use of this technique, a more sparsely sampled dynamic image sequence is reconstructed correctly, without Nyquist foldover artifact. Unlike most other reduced field-of-view (rFOV) methods, Noquist does not rely on data substitution or temporal interpolation to reconstruct the dynamic image sequence. The proposed method reduces acquisition time in dynamic MRI scans by eliminating the data redundancy associated with static regions in the dynamic scene. A reduction of imaging time is achieved by a fraction asymptotically equal to the static fraction of the FOV, by omitting acquisition of an appropriate subset of phase-encoding views from a conventional equidistant Cartesian acquisition grid. The theory behind this method is presented along with sample reconstructions from real and simulated data. Noquist is compared with conventional cine imaging by retrospective selection of a reduced data set from a full-grid conventional image sequence. In addition, a comparison is presented, using real and simulated data, of our technique with an existing rFOV technique that uses temporal interpolation. The experimental results confirm the theory, and demonstrate that Noquist reduces scan time for cine MRI while fully preserving both spatial and temporal resolution, but at the cost of a reduced signal-to-noise ratio (SNR).     

Diagnosis of patent foramen ovale with multiplane transesophageal echocardiography in adult cardiac surgical patients

OBJECTIVE: To evaluate multiplane transesophageal echocardiography (TEE) for detection of patent foramen ovale (PFO) and to compare multiplane TEE with visual inspection (VI) for PFO detection. DESIGN: A prospective observational study. SETTING: University hospital (single institution). PARTICIPANTS: Patients presenting for cardiac surgery requiring TEE. INTERVENTIONS: Multiplane TEE including 2 atrial views with color-flow Doppler (CFD) and contrast echocardiography (CE) with a provocative respiratory maneuver (PRM) and comparison of multiplane TEE and VI with respect to PFO detection. MEASUREMENTS AND MAIN RESULTS: The cohort size was 187. PFO prevalence was 27.3%. CFD with serial decrease of the Nyquist limit detected 51% of all PFO: 41.2% in the bicaval view alone, 27.5% in the 4-chamber view alone, and 9.8% in both views. CE detected 78.4% of all PFO: 72.5% with PRM, 45.1% with no PRM, and 27.4% with/without PRM. PFO detection by multiplane TEE and visual inspection were correlated in 41 subjects. TEE diagnosed 11 PFO (26.8% prevalence, 3 missed by VI). VI diagnosed 12 PFO (29.3% prevalence, 4 missed by TEE). CONCLUSIONS: Multiplane TEE is a gold standard for detection of PFO. Despite advances in TEE technology, 2-dimensional imaging does not detect all PFO. To maximize PFO detection, multiple TEE modalities are required in multiple views, despite a low Nyquist limit for CFD or a PRM for CE. Even though multiplane TEE is equivalent to VI for PFO detection, the discrepancy rate may be an important consideration in the individual case.     

Evaluation of the binding of the tricyclic isoxazole photoaffinity label LY475776 to multidrug resistance associated protein 1 (MRP1) orthologs and several ATP- binding cassette (ABC) drug transporters

Several of the ATP-binding cassette (ABC) transporters confer resistance to anticancer agents and/or antiviral agents when overexpressed in drug-sensitive cells. Recently a MRP1 (ABCC1) tricyclic isoxazole inhibitor, LY475776 was shown to be a glutathione-dependent photoaffinity label of human MRP1 and showed poor labeling of murine mrp1, an ortholog that does not confer anthracycline resistance. In the present study, the specificity of LY475776 was examined for its ability to modulate or photolabel orthologs of MRP1 and several other drug efflux transporters of the ABC transporter family. LY475776 modulated MRP1 and Pgp-mediated resistance (MDR, ABCB1) in, respectively, HeLa-T5 and CEM/VLB(100) cells to both vincristine and doxorubicin. LY475776 photolabeled 170kDa Pgp and was inhibited by the potent Pgp inhibitor LY335979 (Zosuquidar.3HCl). The labeling of the 190kDa MRP1 protein in membranes of HeLa-T5 cells was inhibited by substrates of MRP1 such as leukotriene C(4), vincrisine, and doxorubicin and by the inhibitor, MK571. LY475776 did not photolabel human MRP2 (ABCC2), MRP3 (ABCC3), MRP5 (ABCC5) or breast cancer resistance protein (ABCG2). Because LY475776 photolabels murine mrp1 less well than human MRP1 and binds to a region believed important for anthracycline binding, studies were conducted with monkey and canine MRP1 which also show a reduced ability to confer resistance to anthracyclines. Unlike murine mrp1, both orthologs were photolabeled well by LY475776. These studies indicate that the specificity of LY475776 is fairly limited to Pgp and MRP1 and further studies will help to define the binding regions.     

Effect of sleep deprivation and driving duration on the useful visual field in younger and older subjects during simulator driving

Nine older subjects (40-51 years) and 10 younger subjects (18-30 years) took part in two one-hour driving sessions. They performed a very monotonous task during which they had to follow a vehicle either after a complete night of sleep or after one night of sleep deprivation. While driving their useful visual field was assessed by introducing signals that would appear on the whole road scene.The analysis of the data indicates that the ability to process peripheral signals deteriorates with age, driving duration and sleep deprivation. However, the effects of these three variables on the peripheral visual ability are not similar in a dual task. The driver's useful visual field changes with age and prolongation of the monotonous driving activity according to a tunnel vision phenomenon. On the other hand, a sleep debt deteriorates the useful visual field according to a general interference phenomenon. These results are discussed in terms of decrease in the level of arousal and increase of fatigue.     

Preventive effect of silymarin against taurolithocholate-induced cholestasis in the rat

Increased amounts of monohydroxylated bile salts (BS) have been found in neonatal cholestasis, parenteral nutrition-induced cholestasis and Byler's disease, among others. We analyzed whether the hepatoprotector silymarin (SIL), administered i.p. at the dose of 100mg/kg/day for 5 days, prevents the cholestatic effect induced by a single injection of the model monohydroxylated BS taurolithocholate (TLC, 30 micromol/kg, i.v.) in male Wistar rats. TLC, administered alone, reduced bile flow, total BS output, and biliary output of glutathione and HCO(3)(-) during the peak of cholestasis (-75, -67, -81, and -80%, respectively, P<0.05). SIL prevented partially these alterations, so that the drops of these parameters induced by TLC were of only -41, -25, -60, and -64%, respectively (P<0.05 vs. TLC alone); these differences between control and SIL-treated animals were maintained throughout the whole (120 min) experimental period. Pharmacokinetic studies showed that TLC decreased the intrinsic fractional constant rate for the canalicular transport of both sulfobromophthalein and the radioactive BS [14C]taurocholate by 60 and 68%, respectively (P<0.05), and these decreases were fully and partially prevented by SIL, respectively. SIL increased the hepatic capability to clear out exogenously administered TLC by improving its own biliary excretion (+104%, P<0.01), and by accelerating the formation of its non-cholestatic metabolite, tauromurideoxycholate (+70%, P<0.05). We conclude that SIL counteracts TLC-induced cholestasis by preventing the impairment in both the BS-dependent and -independent fractions of the bile flow. The possible mechanism/s involved in this beneficial effect will be discussed.     

Further studies on the interaction of nonpolyglutamatable aminopterin analogs with dihydrofolate reductase and the reduced folate carrier as determinants of in vitro antitumor activity

Thirteen structural analogs of the potent nonpolyglutamatable dihydrofolate reductase inhibitor N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-ornithine (PT523) with modifications in the side chain, the para-aminobenzoyl moiety, or the 9,10-bridge were evaluated for the ability to inhibit human recombinant dihydrofolate reductase (DHFR), to utilize the reduced folate carrier (RFC) for influx, and to inhibit the growth of CCRF-CEM human leukemia cells in culture. In spectrophotometric assays of the kinetics of the reduction of dihydrofolate by DHFR in the presence of NADPH, these compounds had K(i) values ranging from 0.2 to 1.3pM, and thus were not greatly different in potency from the parent drug PT523. By comparison, the K(i) values of aminopterin (AMT), methotrexate (MTX), and 10-ethyl-10-deazaaminopterin (EDX) were 3.7, 4.8, and 11pM. In assays of competitive inhibition of [3H]MTX influx into CCRF-CEM cells, the K(i) values ranged from 0.21 to 7.3 micro M, as compared with 0.71, 5.4, and 1.1 micro M for PT523, AMT, and EDX. The K(t) for MTX was also re-analyzed and found to be 4.7 micro M, in better agreement with the literature than our previously reported value of 7.1 micro M. The IC(50) values of these compounds as inhibitors of the growth of CCRF-CEM cells after 72hr of drug exposure ranged from 0.53 to 55nM, and were qualitatively consistent with the other results.     

Chronic ethanol consumption impairs receptor-mediated endocytosis of MAA-modified albumin by liver endothelial cells

Alcoholic liver disease has been associated with abnormalities in receptor-mediated endocytosis (RME) which results in abnormal degradation of metabolically altered proteins. Model systems using formaldehyde-modified albumin (f-Alb) have shown an impairment in RME following chronic alcohol consumption utilizing both in situ perfused rat livers and isolated rat liver endothelial cells (LECs). The discovery that alcohol metabolite derived aldehydes can modify proteins prompted a study to determine if malondialdehyde-acetaldehyde-modified albumin (MAA-Alb) would be degraded similar to that reported for f-Alb, and whether ethanol-fed rats would demonstrate an impaired RME with respect to this ligand which occurs as a consequence of chronic ethanol consumption. MAA-Alb was degraded slightly more than f-Alb in both in situ perfused livers and at the single cell level. This degradation was completely inhibited with 100x unlabeled f-Alb, which suggests the use of a similar receptor. Following alcohol consumption there was a 50-60% decrease in MAA-Alb degradation in whole livers and isolated LECs. Utilizing isolated LECs it was determined that impairment in internalization was the most likely mechanism for the decrease in the amount of MAA-Alb that was degraded. These data show that chronic alcohol consumption by rats does in fact impair RME of alcohol metabolite-derived adducted proteins, and this impairment is due to a defect in the post-internalization step rather than the binding or degradation of the modified protein.     

Alteration of A(3) adenosine receptors in human neutrophils and low frequency electromagnetic fields

The present study was designed to evaluate the binding and functional characterization of A(3) adenosine receptors in human neutrophils exposed to low frequency, low energy, pulsing electromagnetic fields (PEMFs). Great interest has grown concerning the use of PEMF in the clinical practice for therapeutic purposes strictly correlated with inflammatory conditions. Saturation experiments performed using the high affinity and selective A(3) adenosine antagonist 5N-(4-methoxyphenyl-carbamoyl)amino-8-propyl-2-(2-furyl)pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine ([3H]-MRE 3008F20) revealed a single class of binding sites with similar affinity in control and in PEMF treated human neutrophils (K(D)=2.36+/-0.16 and 2.45+/-0.15 nM, respectively). PEMFs treatment revealed that the receptor density was statistically increased (P<0.01) (B(max)=451+/-18 and 736+/-25fmolmg(-1) protein, respectively). Thermodynamic data indicated that [3H]-MRE 3008F20 binding in control and in PEMF-treated human neutrophils was entropy and enthalpy driven. Competition of radioligand binding by the high affinity A(3) receptor agonists, N(6)-(3-iodo-benzyl)-2-chloro-adenosine-5'-N-methyluronamide (Cl-IB-MECA) and N(6)-(3-iodo-benzyl)adenosine-5'-N-methyl-uronamide (IB-MECA), in the absence of PEMFs revealed high and low affinity values similar to those found in the presence of PEMFs. In both experimental conditions, the addition of GTP 100 microM shifted the competition binding curves of the agonists from a biphasic to a monophasic shape. In functional assays Cl-IB-MECA and IB-MECA were able to inhibit cyclic AMP accumulation and their potencies were statistically increased after exposure to PEMFs. These results indicate in human neutrophils treated with PEMFs the presence of significant alterations in the A(3) adenosine receptor density and functionality.     

在军队医院建设中贯彻科学发展观

本文运用科学发展观所蕴含的世界观和方法论,深刻论述了新世纪新阶段军队医院建设发展面临的新机遇与新挑战、新特点与新规律,提出了与之相对应的军队医院实现又好又快发展的新思路、新方法和新举措,旨在为增强军队医院履行新使命、发挥新作用、开创新局面提供思路与建议。     

扫描视野对乳腺癌调强放射治疗剂量学影响的研究

目的 研究不同扫描视野(FOV)CT图像对乳腺癌根治术后放射治疗中危及器官自动勾画及剂量计算精度的影响。方法 使用相同扫描条件在患者模拟定位CT等中心处及扩展扫描射野(eFOV)处建立50、60、70和80 cm FOV的电子密度转换曲线并比较其差异;扫描已知体积的标准模体,比较模体在不同FOV重建图像上自动勾画的差异。简单随机抽样选取2020年1月至2022年6月广东省第二人民医院乳腺癌患者30例,获取不同FOV模拟定位CT图像进行危及器官自动勾画,并与医师的勾画进行比较;基于FOV₅₀图像设计治疗计划,将计划移植到不同FOV重建图像进行剂量计算,比较剂量计算结果的差异。结果 以不同FOV重建CT图像建立的电子密度转换曲线基本一致。在等中心处,标准模体随FOV增大,模体勾画体积与实际体积差异增大,最大为6 cm³(4.8%);在自动勾画中,脊髓、气管、食管、甲状腺、健侧乳腺和皮肤的勾画精度随FOV增大而减小(t= -28.43~8.23,P＜0.05), 基于不同FOV图像的剂量计算比较中,锁骨上淋巴结区域靶区V₉₅、最大剂量和平均剂量,危及器官剂量学的差异无统计学意义(P>0.05); 计划靶区覆盖度随FOV增大而减小(最大差异为4.06%)。结论 乳腺癌根治术后放疗中危及器官自动勾画应选择FOV₅₀重建图像,电子密度转换曲线应依据eFOV区域电子密度模体影像建立,首选eFOV₈₀的重建图像进行剂量计算。