能谱CT成像对甲状腺癌局部浸润深度的诊断价值及其定量参数与肿瘤组织中Ki67、VEGF、CD34、EGFR的相关性

摘要 目的：探讨能谱CT成像对甲状腺癌局部浸润深度的诊断价值及其定量参数与肿瘤组织中Ki67、VEGF、CD34、EGFR的相关性。方法：回顾性分析2018年6月-2021年6月我院经手术或穿刺活检病理证实为甲状腺肿瘤性病变的患者96例，其中29例为甲状腺癌局部浸润组（A组），34例为甲状腺癌无浸润组（B组），33例为甲状腺腺瘤组（C组）。另取56例甲状腺另一侧叶正常组织作为对照组（D组）。所有患者均完善能谱CT检查，采集图像后在能谱CT Viewer分析软件上测量病变区碘浓度，计算能谱曲线斜率。采用免疫组织化学染色分析Ki-67、VEGF、CD34、EGFR的表达情况。采用Spearman秩相关分析评价碘浓度、能谱曲线斜率与甲状腺癌肿瘤组织中Ki-67、VEGF、CD34、EGFR表达的相关性。结果：在平扫、动脉期、静脉期，A组、B组、C组和D组的碘浓度逐渐增大，两两比较差异均有统计学意义（P＜0.05）。甲状腺癌局部浸润组织能谱曲线呈"低平型"，斜率为较小负值，正常甲状腺组织能谱曲线为下降型，斜率为负值；在平扫、动脉期、静脉期，A组、B组、C组和D组的能谱曲线斜率逐渐变小，差异均有统计学意义（P＜0.05）。A组中Ki-67、VEGF、CD34和EGFR的阳性表达率均高于B组和C组，差异均有统计学意义（P＜0.05）。碘浓度在动脉期、静脉期与Ki-67、VEGF、CD34、EGFR表达呈正相关（P＜0.05），碘浓度在平扫与Ki-67表达呈正相关（P＜0.05），碘浓度在平扫与VEGF、CD34、EGFR表达无相关性（P＞0.05）。能谱曲线斜率在动脉期、静脉期与Ki-67、VEGF、CD34、EGFR表达呈正相关（P＜0.05），能谱曲线斜率在平扫与VEGF表达呈正相关（P＜0.05），能谱曲线斜率在平扫与Ki-67、CD34、EGFR表达无相关性（P＞0.05）。结论：能谱CT成像检查对甲状腺癌局部浸润深度的判断具有重要的价值，其定量参数碘浓度、能谱曲线斜率与Ki67、VEGF、CD34、EGFR具有相关性，可间接反映肿瘤微血管、肿瘤血管生成、甲状腺癌分化程度、浸润程度等情况，对评价甲状腺癌生物学行为可提供有价值的信息。     

Incommensurate frequencies of major vascular regulatory mechanisms.

The dynamic relationship among three major vascular control mechanisms that operate on large fractions of cardiac output: arterial baroreflex and renal and mesenteric autoregulation, was investigated in conscious rats. Wistar and spontaneously hypertensive rats were studied in their home cages 10 days after implantation of pulsed Doppler flow probes. There was an oscillation of blood pressure centered at 0.45 Hz that is associated with operation of arterial baroreflexes. Hindquarters blood flow displayed a featureless, "1/f' power spectrum, in which no autoregulatory or baroreflex signatures could be discerned, although active control of resistance over a wide range of frequencies was evident. The renal pressure - flow transfer function was dominated by an autoregulatory mechanism with a resonance peak at 0.25 +/- 0.01 Hz. In the mesenteric circulation an autoregulatory mechanism was seen with a resonance peak at 0.15 +/- 0.01 Hz and another active mechanism was seen above 0.2 Hz that appeared from its negative admittance phase to be a baroreflex. The center frequencies of mesenteric and renal autoregulation and of the arterial baroreflex were related in a ratio of 1 : 1.7 +/- 0.1 : 3.0 +/- 0.2 (approximately 4:7:12). Such relatively high order ratios can be expected to minimize the possibility of phase locking and (or) entrainment among the various control mechanisms.     

Phase dynamics in cerebral autoregulation

Complex continuous wavelet transforms are used to study the dynamics of instantaneous phase difference delta phi between the fluctuations of arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) in a middle cerebral artery. For healthy individuals, this phase difference changes slowly over time and has an almost uniform distribution for the very low-frequency (0.02-0.07 Hz) part of the spectrum. We quantify phase dynamics with the help of the synchronization index gamma = (sin delta phi)2 + (cos delta phi)2 that may vary between 0 (uniform distribution of phase differences, so the time series are statistically independent of one another) and 1 (phase locking of ABP and CBFV, so the former drives the latter). For healthy individuals, the group-averaged index gamma has two distinct peaks, one at 0.11 Hz [gamma = 0.59 +/- 0.09] and another at 0.33 Hz (gamma = 0.55 +/- 0.17). In the very low-frequency range (0.02-0.07 Hz), phase difference variability is an inherent property of an intact autoregulation system. Consequently, the average value of the synchronization parameter in this part of the spectrum is equal to 0.13 +/- 0.03. The phase difference variability sheds new light on the nature of cerebral hemodynamics, which so far has been predominantly characterized with the help of the high-pass filter model. In this intrinsically stationary approach, based on the transfer function formalism, the efficient autoregulation is associated with the positive phase shift between oscillations of CBFV and ABP. However, the method is applicable only in the part of the spectrum (0.1-0.3 Hz) where the coherence of these signals is high. We point out that synchrony analysis through the use of wavelet transforms is more general and allows us to study nonstationary aspects of cerebral hemodynamics in the very low-frequency range where the physiological significance of autoregulation is most strongly pronounced.     

A retrieval algorithm to evaluate the Photosystem I and Photosystem II spectral contributions to leaf chlorophyll fluorescence at physiological temperatures

A new computational procedure to resolve the contribution of Photosystem I (PSI) and Photosystem II (PSII) to the leaf chlorophyll fluorescence emission spectra at room temperature has been developed. It is based on the Principal Component Analysis (PCA) of the leaf fluorescence emission spectra measured during the OI photochemical phase of fluorescence induction kinetics. During this phase, we can assume that only two spectral components are present, one of which is constant (PSI) and the other variable in intensity (PSII). Application of the PCA method to the measured fluorescence emission spectra of Ficus benjamina L. evidences that the temporal variation in the spectra can be ascribed to a single spectral component (the first principal component extracted by PCA), which can be considered to be a good approximation of the PSII fluorescence emission spectrum. The PSI fluorescence emission spectrum was deduced by difference between measured spectra and the first principal component. A single-band spectrum for the PSI fluorescence emission, peaked at about 735?nm, and a 2-band spectrum with maxima at 685 and 740?nm for the PSII were obtained. A linear combination of only these two spectral shapes produced a good fit for any measured emission spectrum of the leaf under investigation and can be used to obtain the fluorescence emission contributions of photosystems under different conditions. With the use of our approach, the dynamics of energy distribution between the two photosystems, such as state transition, can be monitored in vivo, directly at physiological temperatures. Separation of the PSI and PSII emission components can improve the understanding of the fluorescence signal changes induced by environmental factors or stress conditions on plants.     

Influence of progesterone on arterial blood and CSF acid-base balance in women

To study the mechanism of the action of progesterone on pulmonary ventilation during pregnancy, arterial and cerebrospinal fluid (CSF) acid-base parameters were measured in 59 pregnant and 36 nonpregnant women at the periods of follicular phase, luteal phase, early pregnancy, late pregnancy, and puerperium. Marked respiratory alkalosis in both arterial blood and CSF was observed in pregnancy and puerperium. The degree of hypocapnia observed in the luteal phase and during pregnancy was closely related to the progesterone level in arterial blood. In conclusion, it is unlikely that the observed hyperventilation results from stimulation at the central chemosensitive areas or peripheral chemoreceptors.     

Analysis of multi-component fluorescence emission by phase-sensitive detection using one modulation frequency

We describe the use of phase-sensitive detection of fluorescence to resolve the lifetimes and fractional intensities from multi-component fluorescence samples, using data obtained at a single modulation frequency. Phase-sensitive spectra of the mixture are recorded at arbitrarily chosen detector phase angles. The steady-state spectrum of each component must be known. The phase-sensitive spectra are fitted, using a nonlinear least-squares algorithm, to obtain the lifetimes and fractional intensities of each fluorophore in the mixture. Simulations for two- and three-component mixtures are presented to illustrate how the resolution is affected by spectral overlap and lifetime separation. Experimentally, we resolved two- and three-component mixtures of protein-like fluorophores (N-acetyl-L-tyrosinamide, N-acetyl- L-tryptophanamide, indole and 2,3-dimethylindole) using data collected at 30 MHz. These fluorophores have closely spaced lifetimes of 1.5, 2.9, 4.5 and 4.3 ns, respectively, and display extensive spectral overlap. These results demonstrate that phase-sensitive spectra, recorded at only one modulation frequency with a standard phase fluorometer, can be used to resolve multi-component emissions.     

Wavelet and Fourier analysis of ventricular and main arteries pulsations in anesthetized dogs

The purpose of this study was to characterize time-frequency behavior using the Continuous Wavelet Transform (CWT) and Fast Fourier Transform (FFT) to analyze ventricular and arterial pressure signals from anesthetized mongrel dogs. Both ventricular and arterial pressure pulsations were recorded using catheter-tip manometers and the CWT was applied to these signals to obtain module coefficients, associated contours, and the 3-D representation of these modules. FFT was applied to obtain the Fourier spectrum. The mathematical analysis of the cardiovascular pressure pulsations permitted the identification of the evolution of the frequency components for the aortic and pulmonary valve functions as well as the intra-ventricular and respiratory influences on the cardiovascular dynamics. The CWT is a very sensitive and reliable procedure for determining the three-dimensional (time-frequency-amplitude) of the oscillatory phenomena during each cardiac cycle, providing more, although complementary, information than the spectral analysis obtained with the FFT. Thanks to the FFT, exact values in Hz could be found for the different events produced in each cycle, and thus the information provided by CWT could be related to the information provided by FFT. The combination of both mathematical methodologies permitted identification of each component of the analyzed signals. The 3D representation allowed an easy comparison of the relative importance of the complex magnitudes in frequency for the different components of the pulsatile waves.     

植物叶片的相位解析光声光谱和光声相位谱

用相位解析法获得的未损伤植物叶片叶肉组织的光声光谱,与叶片的光声相位谱进行了比较．发现植物叶片的光声相位谱与叶绿体光吸收带之间呈现互补关系．叶片表皮的光声相位谱存在持有的波谷结构．不同调制频率的光声相位谱有较大的差异．这些现象表明光声相位谱与光声光谱一样,也可对未损伤的层状生物样品作深度剖面分析．     

High-speed bubble-segmented blood sampler for the rat

An arterial blood sampler for use in the conscious rat is described. With this apparatus it is possible to obtain small (10 microliter) whole-blood or plasma samples as frequently as 1/s and to derive accurate arterial time-concentration curves in the first 60-120 s after compounds are injected for regional blood flow or pharmacokinetic measurements. The blood is withdrawn from an implanted arterial catheter into polyethylene tubing at a constant rate while bubbles are introduced at regular intervals via a side channel into the column of blood. Although some dispersion of blood samples occurs as the tubing is traversed, this can be mathematically corrected. However, correction is unnecessary if the information of interest is the area under the time-concentration curve.     

Characteristics of myocardial metabolism during induction and prolongation of artificial hypobiosis

Glucose, free fatty acids and lipid fatty acid spectrum were studied in arterial and right atrial blood and myocardium of 122 rats during induction and prolongation of artificial hypobiosis (3 and 24 hours) at body temperature of 30 and 20 degrees C. Prolongation of hypobiosis was shown to be accompanied by enhanced participation of free fatty acids in the myocardial energy metabolism. Lipid fatty acid spectrum in the myocardium was characterized by the decrease in linoleic and palmitooleic acid content and the increase in oleic, palmitic, stearic and arachidonic acid levels.     

Age-related characteristics of intraorganic vascular structures of the cerebral cortex, heart, kidneys and spleen in rats in the normal state and in arterial hypertension

The work has been performed on 40 normotensive and spontaneously hypertensive rats at the age of 6 months-1 year. In all the organs studied a direct dependence between the degree of changes in the intraorganic arterial walls and a relative content of the arterial vessels in the organ tissues has been revealed. The functional changes of the arterial bed of the organs mentioned in spontaneously hypertensive rats during hypertensive phase at the stage of stable hypertension, as a result of a prolonged adaptation transform into organic ones.     

Feasibility Study of Ex Ovo Chick Chorioallantoic Artery Model for Investigating Pulsatile Variation of Arterial Geometry

Despite considerable research efforts on the relationship between arterial geometry and cardiovascular pathology, information is lacking on the pulsatile geometrical variation caused by arterial distensibility and cardiomotility because of the lack of suitable in vivo experimental models and the methodological difficulties in examining the arterial dynamics. We aimed to investigate the feasibility of using a chick embryo system as an experimental model for basic research on the pulsatile variation of arterial geometry. Optical microscope video images of various arterial shapes in chick chorioallantoic circulation were recorded from different locations and different embryo samples. The high optical transparency of the chorioallantoic membrane (CAM) allowed clear observation of tiny vessels and their movements. Systolic and diastolic changes in arterial geometry were visualized by detecting the wall boundaries from binary images. Several to hundreds of microns of wall displacement variations were recognized during a pulsatile cycle. The spatial maps of the wall motion harmonics and magnitude ratio of harmonic components were obtained by analyzing the temporal brightness variation at each pixel in sequential grayscale images using spectral analysis techniques. The local variations in the spectral characteristics of the arterial wall motion were reflected well in the analysis results. In addition, mapping the phase angle of the fundamental frequency identified the regional variations in the wall motion directivity and phase shift. Regional variations in wall motion phase angle and fundamental-to-second harmonic ratio were remarkable near the bifurcation area. In summary, wall motion in various arterial geometry including straight, curved and bifurcated shapes was well observed in the CAM artery model, and their local and cyclic variations could be characterized by Fourier and wavelet transforms of the acquired video images. The CAM artery model with the spectral analysis method is a useful in vivo experimental model for studying pulsatile variation in arterial geometry.     

High pressure 2H nuclear magnetic resonance study of the gel phases of dipalmitoylphosphatidylcholine

The 2H-NMR lineshapes of dipalmitoylphosphatidylcholine perdeuterated in the acyl chains were studied in a 15% dispersion in water as a function of pressure from 1 bar to 5 kbar over the temperature range from 7 degrees C to 75 degrees C. Increasing pressure in the gel state had the same effect as lowering the temperature: the lineshape gradually changed from a motionally averaged to a rigid lattice type spectrum with much of the intensity in the shoulders at +/- 63 kHz. At very high pressures and low temperatures (7 degrees C, 2.5 kbar; 25 degrees C, 5 kbar) even the methyl portion of the spectrum became a rigid lattice type spectrum at +/- 21 kHz. In addition to the liquid crystalline phase, five gel phases were detected. Using different techniques to determine the phase transitions, a general pressure-temperature phase diagram was constructed.     

Feasibility of 4D CT simulation with synchronized intravenous contrast injection in hepatocellular carcinoma

BackgroundDelivering Stereotactic Body Radiotherapy (SBRT) for Hepatocellular Carcinoma (HCC) is challenging mainly for two reasons: first, motion of the liver occurs in six degrees of freedom and, second, delineation of the tumor is difficult owing to a similar density of HCC to that of the adjoining healthy liver tissue in a non-contrast CT scan. To overcome both these challenges simultaneously, we performed a feasibility study to synchronize intravenous contrast to obtain an arterial and a delayed phase 4D CT.Materials and MethodsWe included seven HCC patients of planned for SBRT. 4D CT simulation was performed with synchronized intravenous contrast based on the formula T_{SCAN DELAY} = T_peak – (L₀/Detector Coverage × Cine Duration in Seconds). This was followed by a delayed 4D CT scan.ResultsWe found that, with our protocol, it is feasible to obtain a 4DCT with an arterial and a delayed phase making it comparable to a diagnostic multi-phase CT. The peak HU of the 4D scan and diagnostic CT were similar (mean peak HU 134.2 vs 143.1, p value = 0.58 N.S). Whereas in comparison with a non-contrast CT a significant rise in the peak HU was seen (mean peak 134.2 vs 61.4 p value = .00003).ConclusionA synchronized contrast 4D CT simulation for HCC is safe and feasible. It results in good contrast enhancement comparable to a diagnostic 3D contrast CT scan.     

兔VX2肝癌模型制作改良及影像学评价

目的 对兔VX2 肝癌模型制作进行改良,以用于介入治疗学研究,同时探讨瘤灶的CT 表现及CT 在检测瘤灶中的作用.方法 将VX2瘤细胞接种于兔皮下使其成瘤并传代;新西兰兔24只,以改良嵌插法建立移植性肝癌模型,于建模后7、14、21 d分别行超声、CT及血管造影检查,用于检测兔肝VX2 瘤灶,评估瘤灶生长变化;随后处死动物,进行尸解,评估影像检查结果.结果 24只（100%） 动物以改良嵌插法建立移植性肝癌模型全部成功.瘤灶以种植后2周CT显示最清楚和典型,直径1 cm～2 cm 左右,平扫呈低密度或等密度,动脉早期明显强化,门脉期呈低密度,与周围肝组织分界较清楚.肝动脉造影显示肿瘤富血供.而种植后超过3 周的肿瘤大部分发生坏死.结论 嵌插改良法是一种值得推广的建立移植性肝癌模型的方法;在对瘤灶进行影像学评价上应尽量选择CT检查,接种后1 周左右的瘤灶较小而难以观察;2 周左右呈肝动脉源性血供丰富的约1 cm～2 cm的实体瘤,造影征像为肿瘤血管与肿瘤染色;3 周以上瘤灶大多出现明显示坏死;因此对1～2cm大小的兔VX2 肝癌瘤体,最适合行血管造影检查.     

下肢动脉阻塞性病变多层螺旋CT低剂量扫描成像初探

目的：探讨低剂量CT扫描在下肢动脉脉阻塞性病变诊断中的应用价值。方法：选择127段经DSA确诊的不同部位下肢动脉阻塞性病变行低剂量CT扫描,并采用MPR,VR,MIP等重建方法获得各下肢动脉CTA图像,将CTA图像与DSA图像的诊断结果利用统计学软件SAS8.1行加权Kappa一致性检验,检验水准为：Kaapa.系数大于0.75。结果：所得CTA图像与DSA图像诊断结果的一致性检验的kappa系数为0.8058,两种诊断结果的一致性为优。结论：采用低剂量扫描条件获得高质量的CTA图像在下肢动脉阻塞性病变的诊断上有肯定的价值。     

The Influence of Hypoxia on the Concentrations of Cyclic Nucleotides in the Rat Brain

Abstract: In order to study the influence of hypoxia on cyclic nucleotides in the brain, we reduced arterial Po, for 15–30 min in lightly anaesthetised and artificially ventilated rats to obtain values ranging from about 45 to about 10 mm Hg. In an additional group (arterial Po₂ 18–22 mm Hg), the tissue hypoxia was aggravated by moderate arterial hypotension (mean arterial blood pressure about 80 mm Hg). In all animals, electrocortical activity was recorded. Cyclic GMP concentrations in cerebral cortex were unchanged in all groups but one. In that group, in which tissue hypoxia was severe enough to induce a suppression-burst EEG pattern and a measurable reduction in the adenylate energy charge, cyclic GMP concentrations were slightly increased ( p < 0.05). Cyclic AMP concentrations remained unaltered at all degrees of hypoxia studied. It is concluded that changes in cyclic nucleotides in brain tissue occur first at such severe degrees of hypoxia of the duration studied that function and metabolism are profoundly altered.     

Quantitative Measurement of Cerebral Oxygen Extraction Fraction Using MRI in Patients with MELAS

Objective

To quantify the cerebral OEF at different phases of stroke-like episodes in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) by using MRI.

Methods

We recruited 32 patients with MELAS confirmed by gene analysis. Conventional MRI scanning, as well as functional MRI including arterial spin labeling and oxygen extraction fraction imaging, was undertaken to obtain the pathological and metabolic information of the brains at different stages of stroke-like episodes in patients. A total of 16 MRI examinations at the acute and subacute phase and 19 examinations at the interictal phase were performed. In addition, 24 healthy volunteers were recruited for control subjects. Six regions of interest were placed in the anterior, middle, and posterior parts of the bilateral hemispheres to measure the OEF of the brain or the lesions.

Results

OEF was reduced significantly in brains of patients at both the acute and subacute phase (0.266 ± 0.026) and at the interictal phase (0.295 ± 0.009), compared with normal controls (0.316 ± 0.025). In the brains at the acute and subacute phase of the episode, 13 ROIs were prescribed on the stroke-like lesions, which showed decreased OEF compared with the contralateral spared brain regions. Increased blood flow was revealed in the stroke-like lesions at the acute and subacute phase, which was confined to the lesions.

Conclusion

MRI can quantitatively show changes in OEF at different phases of stroke-like episodes. The utilization of oxygen in the brain seems to be reduced more severely after the onset of episodes in MELAS, especially for those brain tissues involved in the episodes.     

Deuterium magnetic resonance study of the gel and liquid crystalline phases of dipalmitoyl phosphatidylcholine.

Deuterium magnetic resonance is applied to the study of the liquid crystalline and gel phases, and of the phase transition, of a multilamellar dispersion of chain perdeuterated (d62)-dipalmitoyl phosphatidylcholine/H2O. Analysis of the deuterium spectra in terms of the moments of the spectra allows one to make quantitative statements concerning the distribution of quadrupolar splittings even in complicated situations, e.g., when using perdeuterated sampled or when there are mixed phases. This analysis indicates that d62-dipalmitoyl phosphatidylcholine in excess H2O undergoes a sharp phase transition (with a width of less than 1 degree C) at approximately 37 degrees C and that there appears to be hysteresis in the phase transition of approximately 1 degree C. In the lamellar liquid crystalline phase above 37 degrees C the spectra show a number of well-resolved features whose quadrupolar splittings can be followed as the temperature is varied. The gel phase near 20 degrees C possesses a very broad, almost featureless spectrum that does not seem to support a model of the gel phase wherein the hydrocarbon chains are fully extended in the all-trans conformation. At temperatures near 0 degrees C the spectra clearly indicate that a large fraction of the lipid molecules cease the rotation about their long axes, giving a spectrum more characteristic of a rigid or solid sample. These results give a picture of the gel phase as a phase characterized by considerable hydrocarbon chain disorder near 20 degrees C and becoming a more solid-like phase near 0 degrees C. The spin-lattice relaxation time, T1, has been measured at 20 degrees C in the gel phase, and at 37 and 45 degrees C in the liquid crystalline phase. The values of T1 obtained for each of the resolvable peaks in the spectrum at 37 degrees C are compared to the values (for each peak) of T2e, the decay time of the quadrupolar echo, obtained at the same temperature. These results are discussed in terms of a simple two-motion model.