Blood oxygenation level-dependent (BOLD) MRI of human skeletal muscle at 1.5 and 3 T

Purpose:

To evaluate the dependence of skeletal muscle blood oxygenation level‐dependent (BOLD) effect and time course characteristics on magnetic field strength in healthy volunteers using an ischemia/reactive hyperemia paradigm.

Materials and Methods:

Two consecutive skeletal muscle BOLD magnetic resonance imaging (MRI) measurements in eight healthy volunteers were performed on 1.5 T and 3.0 T whole‐body MRI scanners. For both measurements a fat‐saturated multi‐shot multiecho gradient‐echo EPI sequence was applied. Temporary vascular occlusion was induced by suprasystolic cuff compression of the thigh. T2* time courses were obtained from two different calf muscles and characterized by typical curve parameters. Ischemia‐ and hyperemia‐induced changes in R2* (ΔR2*) were calculated for both muscles in each volunteer at the two field strengths.

Results:

Skeletal muscle BOLD changes are dependent on magnetic field strength as the ratio ΔR2*(3.0 T)/ΔR2*(1.5 T) was found to range between 1.6 and 2.2. Regarding time course characteristics, significantly higher relative T2* changes were found in both muscles at 3.0 T.

Conclusion:

The present study shows an approximately linear field strength dependence of ΔR2* in the skeletal muscle in response to ischemia and reactive hyperemia. Using higher magnetic fields is advisable for future BOLD imaging studies of peripheral limb pathologies. J. Magn. Reson. Imaging 2012;35:1227‐1232. © 2012 Wiley Periodicals, Inc.     

Measurement of skeletal muscle perfusion during postischemic reactive hyperemia using contrast-enhanced MRI with a step-input function.

The regional distribution of skeletal muscle blood flow was measured during postischemic reactive hyperemia using Gd-DTPA contrast-enhanced (CE) MRI. The release of an occlusive thigh cuff was used to deliver a step-input of contrast concentration that was coincident with the onset of reactive hyperemia. A first-order tracer kinetic equation was used to estimate the unidirectional influx constant, Ki (ml/100 g/min), and the distribution volume of Gd-DTPA in the tissue, v(e), from T1-weighted images acquired with saturation recovery (SR) steady-state free precession (SSFP) and spoiled gradient-echo (SPGR) protocols. The capillary permeability surface (PS) area increased significantly during reactive hyperemia, which facilitated rapid extraction of Gd-DTPA during the first pass. Regional muscle group studies from 11 normal volunteers yielded blood flow (Ki) values of 108.3 +/- 34.1 ml/100 g/min in the gastrocnemius, 184.3 +/- 41.3 ml/100 g/min in the soleus, and 122.4 +/- 34.4 ml/100 g/min in the tibialis anterior. The distribution volumes (v(e)) in the corresponding muscle groups were respectively 8.3% +/- 2.1%, 9.3% +/- 1.9%, and 7.9% +/- 1.8% from the kinetic model, and 8.8% +/- 2.4%, 9.1% +/- 1.9%, and 7.2% +/- 1.4% from tissue relaxometry studies. Bulk blood flow studies in the same volunteers using phase-contrast velocimetry (popliteal artery) yielded significantly lower flow values, but with a correlation coefficient R2 = 0.62 and P = 0.004.     

Calf muscles imaged at BOLD MR: correlation with TcPO2 and flowmetry measurements during ischemia and reactive hyperemia--initial experience

PURPOSE: To prospectively compare the blood oxygen level-dependent (BOLD) magnetic resonance (MR) signal intensity of calf muscle during ischemia and reactive hyperemia with laser Doppler flowmetry (LDF) and transcutaneous oxygen pressure (TcPo2) measurements, two parameters routinely used to evaluate peripheral arterial occlusive disease. MATERIALS AND METHODS: The study was institutional review board approved; all volunteers gave informed consent. Fifteen healthy volunteers (eight male, seven female; mean age, 33.0 years +/- 6.1 [standard deviation]) underwent LDF, TcPo2 measurement, and BOLD MR imaging of the calf during ischemia and reactive hyperemia. The BOLD signal intensity of the gastrocnemius muscle was measured at 1.5-T single-shot multiecho gradient-echo echo-planar imaging. Time to half ischemia minimum (THIM), time to half hyperemia peak (THHP), and time to peak (TTP) after cuff deflation were measured with each method. Correlation coefficients (CCs) for associations of BOLD response with LDF and TcPo2 time courses were calculated. Student t testing of key BOLD MR, LDF, and TcPo2 measurement parameters was performed. RESULTS: During ischemia, normalized LDF and TcPo2 measurements decreased similarly to BOLD MR signal intensity (CCs: 0.86 and 0.96 for associations with LDF and TcPo2 measurements, respectively). Mean THIM values were 136.0, 82.5, and 121.3 seconds for BOLD MR, LDF (P < .01), and TcPo2 (P > .05) measurements, respectively. During early reactive hyperemia, LDF and TcPo2 measurements increased rapidly to peak values, similarly to BOLD MR signal intensity (CCs: 0.81 and 0.78, respectively). Mean THHP values were 26.0, 12.5, and 44.0 seconds for BOLD MR, LDF (P < .01), and TcPo2 (P < .01) measurements, respectively. Mean TTP values were 48.7, 47.5, and 98.0 seconds for BOLD MR, LDF (P > .05), and TcPo2 (P < .01) measurements, respectively. CONCLUSION: BOLD MR imaging of calf muscles-depending on underlying key parameters-has moderate to good correlation with LDF and TcPo2 measurements during ischemia and reactive hyperemia.     

Influence of vascular filling and perfusion on BOLD contrast during reactive hyperemia in human skeletal muscle.

Mechanisms generating BOLD contrast are complex and depend on parameters that are prone to large variations, in particular in skeletal muscle. Here, we simultaneously measured perfusion by ASL, and BOLD response in the calf muscle of 6 healthy volunteers during post-ischemic reactive hyperemia. We tested whether the relation between the two was altered for varying degrees of leg vascular replenishment induced by prior positioning of the leg at different heights relative to the heart. We found that the BOLD response depended on perfusion, but also on the degree of repletion of leg blood vessels. We conclude that simultaneous determination of perfusion by ASL is important to identify the mechanisms underlying BOLD contrast in the skeletal muscle.     

Fast monitoring of T(1) , T(2) , and relative proton density (M(0) ) changes in skeletal muscles using an IR-TrueFISP sequence

Purpose:

To investigate the feasibility of fast and simultaneous assessment of T₁, T₂, and M₀ (relative proton density) changes in skeletal muscle studies using an inversion recovery true fast imaging with steady‐state precession (TrueFISP) sequence.

Materials and Methods:

NMR signal dynamics in calf muscles were analyzed under four different conditions: intravenous injection of a low‐molecular weight Gd contrast agent (CA), postarterial occlusion reactive hyperemia, local cooling, and an exercise bout. Experiments were conducted on a clinical 3T whole‐body scanner.

Results:

At rest, average muscle T₁ and T₂ values obtained from the IR‐TrueFISP experiments were 1.34 ± 0.13 seconds and 45 ± 5 msec, respectively (median ± standard deviation). 1) Noticeable T₁ decreases (ΔT₁ max ≈?30%) were measured in the calf muscles after CA injection, while no significant changes were observed for T₂ and M₀. 2) T₂ increased rapidly during reactive hyperemia and reached a peak value (+6%) at about 1 minute postischemia. During ischemia, a significant decrease was observed only in the soleus muscle. No significant paradigm‐related changes in M₀ and T₁ were noted in all muscle groups, except in the m. soleus (ΔT₁ ≈+1% during reactive hyperemia). 3) Opposite variations in muscle T₁ (ΔT₁ max ≈?30%) and M₀ (ΔM₀ max ≈+25%) associated with local cooling were detected. 4) Concomitant changes in T₁ (ΔT₁ max ≈+15%), T₂ (ΔT₂ max ≈+35%), and M₀ (ΔM₀ max ≈+16%) were observed in the activated muscles following the exercise bout.

Conclusion:

IR‐TrueFISP was sufficiently fast and sensitive to detect small and transient T₁, T₂, and M₀ changes in the calf muscles under different experimental conditions. The sequence offers a time‐resolution adequate to track rapid physiological adaptations in skeletal muscle. J. Magn. Reson. Imaging 2011;33:921–930. © 2011 Wiley‐Liss, Inc.

     

NMR imaging of changes in vascular morphology due to tumor angiogenesis

Tumor-sprouted vessels are greater in both number and diameter in comparison to their healthy counterparts. A novel technique based on magnetic susceptibility contrast mechanisms that are sensitive to varying sizes of blood vessels is presented to measure differences between the relaxation rates (1/T₂ and 1/T) in a rat glioma model and normal cerebral cortex. ΔR2 and ΔR2*, the differences between relaxation rates precontrast and postcontrast agent injection, were measured for an intravascular equilibrium contrast agent (MION) at various echo times. Since ΔR2*/ΔR2 increases as vessel size increases, this ratio can be used as a measure of the average vessel size within an ROI or a voxel. The stability and longevity of the contrast agent within the vasculature were verified (n = 2 trials), and the ratio of ΔR2*/ΔR2 between the tumor and normal cortex was measured to be 1.9 ± 0.2 (n = 4, echo time = 20 ms, and susceptibility difference (Δχ) ≈? 10^?6). This ratio compared favorably to a predicted ratio determined using histologically determined vessel sizes and theoretical Monte Carlo modeling results (1.9 ± 0.1). Maps of the ratio of ΔR2*/ΔR2 were also made on a pixel-by-pixel basis. These techniques support the hypothesis that susceptibility contrast MRI can provide useful quantitative metrics of in vivo tumor vascular morphology.     

Spin-echo MRI underestimates functional changes in microvascular cerebral blood plasma volume using exogenous contrast agent.

While most functional MRI studies using exogenous contrast agent employ gradient-echo (GE) signal, spin echo (SE) imaging would represent an attractive alternative if its detection power were more comparable with GE imaging. This study demonstrates that SE methods systematically underestimate functional changes in microvascular cerebral blood plasma volume (CBV), so that SE detection power in brain tissue cannot match that provided by GE signal. Empirically, the in vivo response of SE-CBV was about 40% smaller than that of GE-CBV in rat brain at low basal values of CBV, a result that is consistent with physics predictions under the simplifying assumption of uniform vessel dilation. However, increasing values of basal CBV were associated with monotonically increasing mean vessel sizes and monotonically decreasing GE to SE ratios of functional changes in CBV (fCBV). This result suggests the presence of large but weakly reactive conduit vessels at high basal values of CBV. Hence, we conclude that GE imaging is the method of choice for functional MRI (fMRI) using exogenous contrast agent in most cases, although SE methods may represent a more spatially linear representation of underlying neural activity that becomes most apparent in regions with high basal CBV, such as the cortical surface.     

Utility of simultaneously acquired gradient-echo and spin-echo cerebral blood volume and morphology maps in brain tumor patients.

An interleaved gradient-echo (GE) / spin-echo (SE) EPI sequence was used to acquire images during the first pass of a susceptibility contrast agent, in patients with brain tumors. Maps of 1) GE (total) rCBV (relative cerebral blood volume), 2) SE (microvascular) rCBV, both corrected for T(1) leakage effects, and 3) (DeltaR(2)*/DeltaR(2)), a potential marker of averaged vessel diameter, were determined. Both GE rCBV and DeltaR(2)*/DeltaR(2) correlated strongly with tumor grade (P = 0.01, P = 0.01, n = 15), while SE rCBV did not (P = 0.24, n = 15). When the GE rCBV data were not corrected for leakage effects, the correlation with tumor grade was no longer significant (P = 0.09, n = 15). These findings suggest that MRI measurements of total blood volume fraction (corrected for agent extravasation) and DeltaR(2)*/DeltaR(2), as opposed to maps of microvascular volume, may prove to be the most appropriate markers for the evaluation of tumor angiogenesis (the induction of new blood vessels) and antiangiogenic therapies. Magn Reson Med 43:845-853, 2000.     

Perfusion changes in human skeletal muscle during reactive hyperemia measured by echo-planar imaging

Muscle performance is markedly influenced by tissue perfu-sion. Techniques that allow quantification of microvascular flow are limited by the use of ionizing radiation. In this investigation, we apply an NMR model previously developed by Detre ef al. to the measurement of human muscle perfusion during reactive hyperemia. We compare our results with conventional plethysmography adapted to NMR. Using echo-planar imaging, T₁ and T₂ were measured in 14 subjects during rest, ischemia, and reactive hyperemia. Mean leg muscle T₁ in healthy volunteers is 850 ms at rest and 834 ms at reperfusion, leading to a calculated reactive hyperemia flow increase (T₁ flow) of 103 ± 40 ml/100 ml/min. T₁ flows correlate well with NMR-plethysmography values. Changes in T₂, which are sensitive to both deoxyhemoglobin content and vessel diameter variations, are also correlated with perfusion measurements. T₁ changes allow quantification of regional perfusion in human muscle during reactive hyperemia.     

Vascular smooth muscle: integrator of vasoactive signals during exercise hyperemia

The primary focus of this review is to discuss the importance of vascular smooth muscle function in mechanisms underlying exercise hyperemia in skeletal muscle. Important features of exercise hyperemia are presented and include: 1) the large magnitude of increase in blood flow, 2) the pattern of increased blood flow within and among skeletal muscle during exercise, 3) exercise hyperemia results from increases in vascular conductance produced by relaxation of vascular smooth muscle, 4) the increased blood flow is linked to the oxidative metabolism of the muscle, and 5) the increased blood flow occurs very rapidly with the initiation of exercise. A prevailing theme throughout this review is that vascular smooth muscle is a primary integrator of vasoactive signals that, in turn, regulate vascular resistance and muscle blood flow. Signal transduction pathways involved in vascular smooth muscle contraction and relaxation are discussed, with particular emphasis on the role of multiple and redundant signaling pathways for initiating a given contractile/relaxation response. We emphasize the concept that exercise hyperemia is a local phenomenon and that, during maximal exercise when most signals for vasoconstriction are still present, three primary control mechanisms are thought to regulate vasodilation and subsequent increases in vascular conductance: myogenic vascular control, metabolic vascular control, and endothelium-mediated vascular control. Experimental paradigms to test the relative importance of the predominant mechanisms thought to underlie exercise hyperemia are discussed and evaluated in light of the multiple and redundant control systems now known to contribute to control of blood flow in striated muscle tissue.     

Continuous assessment of relative cerebral blood volume in transient ischemia using steady state susceptibility-contrast MRI

The utility of a noninvasive steady state susceptibility-contrast MRI technique for continuous measurement of relative cerebral blood volume (rCBV) during global transient ischemia and subsequent hyperemia in a feline ischemia model is demonstrated. The measurements were obtained during a 10-min period of occlusion and 1-h period of reperfusion. Maximal hyperemic responses in gray matter, basal ganglia, and white matter (observed at 7,7, and 5 min, respectively) were 1.9 ± 0.5,1.8 ± 0.3, and 1.7 ± 0.6 times greater than baseline CBV (mean ± SEM). Thirty to forty minutes after onset of reperfusion, CBV returned to normal. Thereafter, it decreased below baseline, nearing the control level by 1 h after onset of reperfusion. Steady state susceptibility-contrast MRI permits continuous, in vivo mapping of alterations in CBV.     

Dynamic hysteresis between gradient echo and spin echo attenuations in dynamic susceptibility contrast imaging

Perfusion measurements using dynamic susceptibility contrast imaging provide additional information about the mean vessel size of microvasculature when supplemented with a dual gradient echo (GE) – spin echo (SE) contrast. Dynamic increase in the corresponding transverse relaxation rate constant changes, ΔR_2GE and ΔR_2SE, forms a loop on the (Δ, ΔR_2GE) plane, rather than a reversible line. The shape of the loop and the direction of its passage differentiate between healthy brain and pathological tissue, such as tumour and ischemic tissue. By considering a tree model of microvasculature, the direction of the loop is found to be influenced mainly by the relative arterial and venous blood volume, as well as the tracer bolus dispersion. A parameter Λ is proposed to characterize the direction and shape of the loop, which might be considered as a novel imaging marker for describing the pathology of cerebrovascular network. Magn Reson Med 69:981–991, 2013. © 2012 Wiley Periodicals, Inc.     

DTI-based assessment of ischemia-reperfusion in mouse skeletal muscle.

Diffusion tensor imaging (DTI) is frequently applied to characterize the microscopic geometrical properties of tissue. To establish whether and how diffusion MRI responds to transient ischemia of skeletal muscle, we studied the effects of ischemia and reperfusion using DTI and T2-weighted MRI before and during ischemia and up to 24 hr after reperfusion. Ischemia was induced by 50 min of hindlimb occlusion with or without dorsal flexor stimulation. During ischemia the apparent diffusion coefficient (ADC) tended to decrease (up to 15%), whereas the fractional anisotropy (FA) and T2 showed a varied response depending on the protocol and muscle type. During reperfusion the ADC and T2 initially increased and subsequently renormalized for the occlusion protocol. For the occlusion plus stimulation (OS) protocol, the FA was decreased by 13% and the ADC and T2 were increased by 20% and 57%, respectively, after 24 hr in the stimulated muscle complex. In the latter tissue the three DTI eigenvalues gradually increased upon reperfusion. The smallest eigenvalue (lambda3) showed the largest relative increase. Changes in DTI indices in the reperfusion phases followed a similar time course as the changes in T2. The changes in MR indices after 24 hr correlated with the tissue damage quantified with histology. The highest correlation was observed for lambda3 (R2 = 0.81). This study shows that DTI can be used to assess ischemia-induced damage to skeletal muscle.     

Thermographic assessment of intestinal viability following ischemic damage

Reactive hyperemia has been shown to be a characteristic of viable ischemic tissue that has been revascularized. A segment of small bowel was made ischemic by arterial occlusion and the ischemia maintained for 2 1/2 hrs (ischemic, viable bowel) or 8 hrs (ischemic, nonviable bowel) before circulation was restored. Thermograms and surface temperature measurements of exposed ischemic and non-ischemic bowel segments were obtained before and every five minutes after revascularization. Thermograms of segments revascularized after 2 1/2 hrs of ischemia demonstrated reactive hyperemia and a one to four degree increase in surface temperature compared to normal surrounding bowel. No hyperemic response was seen in bowel segments that were ischemic for 8 hrs. Our results indicate that thermograms can document reactive hyperemia of an exposed ischemic bowel that has been successfully revascularized and may be an important aid in assessing bowel viability during surgery.     

Alterations in T1 of normal and reperfused infarcted myocardium after Gd-BOPTA versus GD-DTPA on inversion recovery EPI

This study tested whether Gd-BOPTA/Dimeg or Gd-DTPA exerts greater relaxation enhancement for blood and reperfused infarcted myocardium. Relaxivity of Gd-BOPTA is increased by weak binding to serum albumin. Thirty-six rats were subjected to reperfused infarction before contrast (doses = 0.05, 0.1, and 0.2 mmol/kg). ΔR1 was repeatedly measured over 30 min. Gd-BOPTA caused greater ΔR1 for blood and myocardium than did Gd-DTPA clearance of both agents from normal and infarcted myocardium was similar to blood clearance; plots of ΔR1myocardium/ΔR1blood showed equilibrium phase contrast distribution. Fractional contrast agent distribution volumes were approximately 0.24 for both agents in normal myocardium, 0.98 and 1.6 for Gd-DTPA and Gd-BOPTA, respectively, in reperfused infarction. The high value for Gd-BOPTA was ascribed to greater relaxivity in infarction versus blood. It was concluded that Gd-BOPTA/Dimeg causes a greater ΔR1 than Gd-DTPA in regions which contain serum albumin.     

Gastric emptying during 1 h of cycling and running at 75% VO2max

The purpose of this study was to compare gastric emptying (GE) responses during intense, prolonged cycling and running. It is important to discern whether gastric emptying (GE) responses are exercise-mode specific, since the findings of cycling and running studies are often compared and applied to one another. Ten male biathletes cycled (CY) and ran (R) for 1 h at 75% of their mode-specific VO2max or rested (S) and consumed water (SW, CYW, RW) or a 7% carbohydrate solution (SC, CYC, RC) at a rate of 10 ml.kg-1.h-1 (approximately 180 ml at 0, 15, 30, and 45 min). No differences were found between CYW, CYC, RW, RC, and SC for volume of drink emptied (mean +/- SE) (522.8 +/- 47.9 ml) and GE rate (range, 8.2 +/- 0.9 (RC) to 9.3 +/- 0.6 ml.min-1 (SC]. A mean of 72.7 +/- 5.7% of the total consumed volume was emptied. The GE rate during SW was significantly (P less than 0.05) greater than the other conditions (11.3 +/- 0.4 ml.min-1, 94.0 +/- 1.9% of total consumed volume emptied). Substantial volumes of water and a 7% carbohydrate solution are thus emptied from the stomach during prolonged, intense running and cycling, with no differences in GE between these exercise modes. These data suggest that recommendations concerning GE are reciprocal between running and cycling bouts similar to those in the current study.     

Comparison of strain and shear-wave ultrasounic elastography in predicting the pathological response to neoadjuvant chemotherapy in breast cancers

Objective

To compare the diagnostic performances of strain elastography (SE) and shear-wave elastography (SWE) for predicting response to neoadjuvant chemotherapy (NACT) in patients with breast cancer.

Methods

This prospective study recruited 71 eligible patients from June 2014 to May 2016. All patients provided written informed consent. Tumour stiffness was assessed by the SE strain ratio (R), SWE maximum elasticity (E_max) and SWE mean elasticity (E_mean). Ultrasonic elastography (UE) assessments were performed at each NACT cycle (t1???t6). For the purpose of predicting, the relative changes in elastographic parameters after the first and second NACT cycles were considered as the variables [Δ(t1) and Δ(t2)]. The area under the receiver operating characteristics (AUC) curve was compared.

Results

ΔE_mean(t2) and R2 displayed the best diagnostic performances within their own modalities (AUC?=?0.93 and 0.90 for predicting favourable response to NACT; AUC?=?0.92 and 0.78 for predicting NACT resistance, respectively). There were no significant differences in AUCs for ΔE_mean(t2) and some UE parameters (P?>?0.05). By contrast, ΔE_mean(t2) was significantly superior to all other SE parameters for predicting resistance (P?<?0.05).

Conclusions

SE and SWE exhibited similar performances for predicting favourable NACT responses; SWE was better than SE for predicting NACT resistance.

Key Points

? Elastography parameters after the second NACT cycle showed the best diagnostic performances. ? SWE and SE yielded similar diagnostic performances in predicting favourable responses. ? SWE performed better than SE in predicting the pathological resistance to NACT. ? Discrepant results may be due to the breast thickness and lesion depth.

     

不同缺血时间再灌注损伤对大鼠骨骼肌的影响

目的探讨不同缺血时间再灌注损伤对大鼠骨骼肌的影响。方法选取35只雄性Wistar大鼠,采用单侧夹闭股动脉和压力绷带施压的方法构建下肢骨骼肌缺血再灌注损伤(IRI)模型。根据不同缺血时间分为2 h缺血24 h再灌注(I2R24组)、2.5 h缺血24 h再灌注(I2.5R24组)、3 h缺血24 h再灌注(I3R24组)、4 h缺血24 h再灌注(I4R24组)、假手术组,每组7只。在再灌注终点,收集腓肠肌组织和血浆进行分析。采用湿重/干重比值(W/D)评估组织水肿情况;3-(4,5-二甲基噻唑-2)-2,5二苯基四氮唑溴盐(MTT)检测组织活力;HE染色观察组织病理学变化;免疫荧光染色检测补体C1q和C3b/c沉积、凝血组织因子(TF)表达和纤维蛋白原(FN)沉积、缓激肽受体1(BR1)和BR2表达、内皮血管细胞黏附分子-1(VCAM-1)和E选择素表达、炎症纤维介素蛋白-2(FGL-2)和髓过氧化物酶(MPO)表达;ELISA法检测血浆干扰素-γ(IFN-γ)、白细胞介素-7(IL-7)、IL-18、巨噬细胞炎症蛋白-1α(MIP-1α)、单核细胞趋化蛋白-1(MCP-1)水平。结果延长缺血时间再灌注,组织水肿逐渐加重,I2R24组、I2.5R24组、I3R24组、I4R24组W/D分别为5.3±0.2、6.1±0.3、6.9±0.2、7.6±0.3,高于假手术组的4.5±0.1(P均<0.01)。组织活力逐渐降低,I2R24组、I2.5R24组、I3R24组、I4R24组分别为(62.4±3.5)%、(45.3±3.3)%、(35.4±3.4)%、(27.1±5.9)%,低于假手术组的(93.8±7.2)%(P均<0.01)。病理组织损伤逐渐加重,最重为I4R24组,有严重肌细胞损伤、间质水肿和大量炎性细胞浸润,余依次为I3R24组、I2.5R24组、I2R24组,假手术组肌细胞结构完整、排列整齐。免疫荧光染色提示C1q、C3b/c、FN、BR1、VCAM-1、E选择素、FGL-2水平逐渐升高,由低到高依次为假手术组、I2R24组、I2.5R24组、I3R24组、I4R24组。MPO阳性细胞数/高倍镜(×200)细胞总数的大体比例逐渐升高,从高到低依次为I4R24组、I3R24组、I2.5R24组、I2R24组、假手术组。而TF和BR2表达在各组间无明显改变。血浆IFN-γ、IL-7、IL-18、MIP-1α、MCP-1浓度随缺血时间延长均逐渐升高(P均<0.01),从低到高依次为假手术组、I2R24组、I2.5R24组、I3R24组、I4R24组(P均<0.01)。结论延长缺血时间再灌注增加补体、凝血、激肽、内皮细胞激活及炎症因子释放,从而加重大鼠骨骼肌组织损伤。     

不同缺血时间再灌注损伤对大鼠骨骼肌的影响

目的探讨不同缺血时间再灌注损伤对大鼠骨骼肌的影响。方法选取35只雄性Wistar大鼠,采用单侧夹闭股动脉和压力绷带施压的方法构建下肢骨骼肌缺血再灌注损伤(IRI)模型。根据不同缺血时间分为2 h缺血24 h再灌注(I2R24组)、2.5 h缺血24 h再灌注(I2.5R24组)、3 h缺血24 h再灌注(I3R24组)、4 h缺血24 h再灌注(I4R24组)、假手术组,每组7只。在再灌注终点,收集腓肠肌组织和血浆进行分析。采用湿重/干重比值(W/D)评估组织水肿情况;3-(4,5-二甲基噻唑-2)-2,5二苯基四氮唑溴盐(MTT)检测组织活力;HE染色观察组织病理学变化;免疫荧光染色检测补体C1q和C3b/c沉积、凝血组织因子(TF)表达和纤维蛋白原(FN)沉积、缓激肽受体1(BR1)和BR2表达、内皮血管细胞黏附分子-1(VCAM-1)和E选择素表达、炎症纤维介素蛋白-2(FGL-2)和髓过氧化物酶(MPO)表达;ELISA法检测血浆干扰素-γ(IFN-γ)、白细胞介素-7(IL-7)、IL-18、巨噬细胞炎症蛋白-1α(MIP-1α)、单核细胞趋化蛋白-1(MCP-1)水平。结果延长缺血时间再灌注,组织水肿逐渐加重,I2R24组、I2.5R24组、I3R24组、I4R24组W/D分别为5.3±0.2、6.1±0.3、6.9±0.2、7.6±0.3,高于假手术组的4.5±0.1(P均<0.01)。组织活力逐渐降低,I2R24组、I2.5R24组、I3R24组、I4R24组分别为(62.4±3.5)%、(45.3±3.3)%、(35.4±3.4)%、(27.1±5.9)%,低于假手术组的(93.8±7.2)%(P均<0.01)。病理组织损伤逐渐加重,最重为I4R24组,有严重肌细胞损伤、间质水肿和大量炎性细胞浸润,余依次为I3R24组、I2.5R24组、I2R24组,假手术组肌细胞结构完整、排列整齐。免疫荧光染色提示C1q、C3b/c、FN、BR1、VCAM-1、E选择素、FGL-2水平逐渐升高,由低到高依次为假手术组、I2R24组、I2.5R24组、I3R24组、I4R24组。MPO阳性细胞数/高倍镜(×200)细胞总数的大体比例逐渐升高,从高到低依次为I4R24组、I3R24组、I2.5R24组、I2R24组、假手术组。而TF和BR2表达在各组间无明显改变。血浆IFN-γ、IL-7、IL-18、MIP-1α、MCP-1浓度随缺血时间延长均逐渐升高(P均<0.01),从低到高依次为假手术组、I2R24组、I2.5R24组、I3R24组、I4R24组(P均<0.01)。结论延长缺血时间再灌注增加补体、凝血、激肽、内皮细胞激活及炎症因子释放,从而加重大鼠骨骼肌组织损伤。     

Measurement of regional blood oxygenation and cerebral hemodynamics

An echo planar linewidth mapping technique, Shufflebutt, has allowed temporal measurements of changes in linewidth caused by static inhomogeneities (ΔLWSI) and transverse relaxation rate (ΔR2) in models of hypoxia and hypercapnia. We demonstrate these changes are due to intravascular susceptibility differences(Δ_X) between the blood and tissue. Contrast agent injections at a /Δ_X equivalent to that of deoxygenatetd blood showed a twofold difference between the contrast agent and physiological anoxia values. Hypercapnia decreased both ΔLWSI and ΔR2 consistent with an increase in blood oxygenation. We attribute these findings to constant oxygen extraction during an increase in blood flow, resulting in less deoxygenated venous blood and thus reduced Δ_X. For in vivoperturbations we found that ΔR/ΔR2′ ≈ 0.33, a ratio much different from that measured in whole blood phantoms (ΔR/ΔR2′ ≈ 2). This demonstrates that signal changes in these studies are produced predominantly by dephasing of extravascular protons due to field inhomogeneities produced by intravascular deoxygenated hemoglobin (deoxyHb).