Lung cancer: differentiation of tumor, necrosis, and atelectasis by means of T1 and T2 values measured in vitro

In vitro measurements of T1 and T2 values were performed in surgical specimens from 15 patients with lung cancer. Correlation between histologic results and measured values revealed that different pathologic tissues can be characterized by means of T1 and T2 values. The transverse magnetization decay curve of the lung tissue was multiexponential, which can be explained by two different relaxation times, fast T2 and slow T2. The signal intensity of pathologic lung tissues at different pulse sequences was simulated on a signal intensity gradient graph based on measured values of T1, fast T2, slow T2, and water content. The results showed that T2-weighted sequences were more valuable in discriminating viable lung cancer from necrotic tumor and collapsed lung lesions.     

The origin of biexponential T2 relaxation in muscle water

Two theories have been proposed to explain the multiexponential transverse relaxation of muscle water protons: “anatomical” and “chemical” compartmentation. In an attempt to obtain evidence to support one or the other of these two theories, interstitial and intracellular macromolecular preparations were studied and compared with rat muscle tissue by proton NMR transverse relaxation (T2) measurements. All macromolecule preparations displayed monoexponential T2 decay. Membrane alteration with DMSO/glycerin did not eliminate the biexponential T2 decay of muscle tissue. Maceration converted biexponential T2 decay of muscle tissue to single exponential decay. It is concluded that the observed two component exponential T2 decay of muscle represents anatomical compartmentation of tissue water, probably intracellular versus extracellular.     

Characterization of bleomycin lung injury by nuclear magnetic resonance: correlation between NMR relaxation times and lung water and collagen content.

The response of the NMR relaxation times (T(1), CPMG T(2), and Hahn T(2)) to bleomycin-induced lung injury was studied in excised, unperfused rat lungs. NMR, histologic, and biochemical (collagen content measurement) analyses were performed 1, 2, 4, and 8 weeks after intratracheal instillation of saline (control lungs) or 10 U/kg bleomycin sulfate. The control lungs showed no important NMR, water content, histologic, or collagen content changes. The spin-spin relaxation times for the fast and intermediate components of the CPMG decay (T(2f) and T(2i), respectively) increased 1 week after bleomycin injury (acute inflammatory stage) and then progressively decreased during the following 2-8 weeks (i.e., with the development of the chronic, fibrotic stage of the injury). The slow component (T(2s)) showed no significant changes. The response of T(1) and the slow component of the Hahn T(2) was, on the whole, similar to that of CPMG T(2f) and T(2i). T(1) changes were very small. Lung water content increased 1 week after injury. Histologic and biochemical assessment of collagen showed that collagen content was close to control at 1 week, but markedly increased at 2, 4, and 8 weeks. T(1) and T(2) data were directly correlated with lung water content and inversely correlated with collagen content. Our results indicate that NMR relaxation time measurements (particularly T(2)) reflect the structural changes associated with bleomycin injury. The prolonged T(2) relaxation times observed in the acute stage are related to the presence of edema, whereas the subsequent decrease in these values marks the stage of the collagen deposition (fibrotic stage). CPMG-T(2) and Hahn-T(2) measurements can be valuable as a potentially noninvasive method for characterizing bleomycin-induced lung injury and pathologically related lung disorders.     

The effect of pulmonary edema on proton nuclear magnetic resonance relaxation times

This study was done to determine the effect of permeability pulmonary edema on proton nuclear magnetic resonance (NMR) relaxation times. Permeability edema was induced in rats by the intravenous injection of alloxan in saline. Control animals received only saline. The rats were ventilated through a tracheostomy; and after a time sufficient for the edema to become uniform, they were sacrificed. T1, and T2 and extravascular lung water were measured on lung samples. A linear relationship was found between the relaxation times and the extravascular lung water. Any diffuse alveolar process including pulmonary edema can increase proton density as well. The T1 and T2 relaxation times may be used to distinguish among different causes of increased proton density in the lung.     

Regional effects of repetition time on NMR quantitation of water in normal and edematous lungs

It is well known that pulmonary edema is, in general, spatially nonuniform. Since the NMR spin-lattice relaxation time (T1) is increased by lung edema, the spatial distribution of T1 will be nonuniform. When the repetition time (TR) is short relative to the T1 of edematous lung, lung water content will be underestimated and this underestimation will be spatially nonuniform as well. Therefore, technical artifacts which are a complex function of lung edema and its spatial distribution are expected. We compared overall and regional (topographic) lung water density measurements obtained from living rats (with normal or edematous lungs) using repetition times of 2.0 and 6.2 s (at a magnetic field of 1 T), to quantify this uneven T1 effect for normal and edematous lungs. NMR measurements at TR = 2.0 s underestimated whole lung water density (-rho H2O) TR = 6.2 s) by an average of 7.2% in normal rats and 22.5% in rats with pulmonary edema. Regional -rho H2O underestimation (%delta-rho H2O) varied from 2.2 to 8.8% (groups means) in normal lungs and from 7.3 to 30.8% in edematous lungs. As a result, the interquartile range (of the voxel distribution as a function of rho H2O) underestimated the spatial nonuniformity of lung water density by 28.0% in edematous lungs, likely because of greater loss of NMR signal from high-water-density, long-T1 lung regions. Both %delta-rho H2O and T1 were significantly correlated with -rho H2O at TR = 6.2 s.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multiexponential proton spin-spin relaxation in MR imaging of human brain tumors

In vivo measurements of proton relaxation processes in human brain tumors have been performed by magnetic resonance (MR) imaging using a whole-body superconductive MR scanner, operating at 1.5 T. The T1 and T2 relaxation time measurements were based on a combined Carr-Purcell/Carr-Purcell-Meiboom-Gill sequence with two interleaved repetition times and 32 echoes. First, comparative measurements in the imager and with the spectrometer of relaxation times were performed on phantoms containing fluids of different T1 and T2 to evaluate accuracy. A maximum deviation of approximately 10% was found. Multislicing with a gap width of one slice thickness influenced the accuracy of T1 relaxation measurement. A gap width of at least two times the slice thickness was necessary for reliable determination of T1. No influence on T2 values was observed by multislicing. Second, in human head imaging the multiexponential behavior of the T2 decay curves has been analyzed in each pixel, where the mean square deviation has been used as a criterion to discriminate between mono- and biexponential behavior. Mean values of monoexponential T1 and multiexponential T2 relaxation data for white matter, gray matter, CSF, edema, and tumor were sampled in 12 patients with brain tumors. T2 showed monoexponential behavior in white and gray matter, whereas CSF, edema, and tumor showed distinct biexponentiality. The biexponential analysis generally yields "fast" and "slow" components with T2f = 80 +/- 17 ms and T2s = 2,030 +/- 210 ms for CSF (partial volume effect), T2f = 104 +/- 25 ms and T2s = 677 +/- 152 ms for edematous tissues, T2f = 97 +/- 19 ms and T2s = 756 +/- 99 ms for tumor tissues, respectively. Using a stepwise discriminant analysis by forward selection, the two best discriminating parameters of the multiexponential relaxation analysis for each pair of classification groups have been selected. For the discrimination of edematous and tumor tissues a retrospective overall accuracy of 94% has been found.     

An in vivo NMR imaging determination of multiexponential Hahn T2 of normal lung

We describe the first in vivo imaging determination of normal lung tissue's multiexponential transverse magnetization decay. Normal spontaneously breathing rats were used for the measurements. To obtain motion-insensitive images, we used a modified line scan imaging technique which we call the interleaved line scan (ILS). The ILS overcomes the following difficulties associated with imaging lungs: low signal-to-noise ratio (S/N) due to lung's low proton density and short T2 decay, artifacts associated with cardiac and respiratory motion, and excessively long imaging times with conventional line scan techniques. Using the ILS, a 16-line 32-average image with an 8-s repetition time requires 4.3 min. From a series of 16 Hahn spin-echo images with echo times ranging from 16 to 90 ms, we obtained a two-component T2 decay for normal peripheral lung tissue. The measured fast and slow T2 components were 9.5 +/- 1.0 and 34 +/- 5.0 ms for the right lung and 9.0 +/- 1.5 and 32 +/- 4.5 for the left lung. The relative magnetization for the slow T2 component was 7.0 +/- 4.5% for the right lung and 10 +/- 3.0% for the left lung.     

Pulmonary edema: an MR study of permeability and hydrostatic types in animals

Permeability pulmonary edema was induced in ten rats by intravenous injection of oleic acid. Hydrostatic pulmonary edema was induced in another ten rats by continuous infusion of saline. Permeability pulmonary edema was detected as increased signal intensity in all animals on images obtained with repetition times (TR) of 2.0 sec and echo times (TE) of 28 and 56 msec. Hydrostatic pulmonary edema was perceivable only in seven of ten rats. It was best seen on spin-echo TR = 2.0 sec, TE = 28 msec images as increased intensity either throughout the whole lung or in a predominant central distribution. The slopes of the relationships between the mean signal intensity and water content of both lungs were lower for hydrostatic pulmonary edema than for permeability pulmonary edema. Hydrostatic pulmonary edema demonstrated similar T1 but markedly shorter T2 relaxation times than permeability edema. Magnetic resonance imaging can be used to estimate severity of hydrostatic and permeability pulmonary edemas.     

A 1-year time course study of the relaxation times and histology for irradiated rat lungs

To investigate the NMR relaxation times for irradiated rat lung tissue, we measured T1 and T2 at 11 different times during the injury's 1-year time course. A biexponential analysis of T2 was used to determine T2 fast (T2f) and T2 slow (T2s). In addition, we measured water content and correlated changes in the relaxation times with pathological changes. The correlation indicates the following: (1) Shortly after irradiation, the biexponential T2 decay for 1/3 of the samples became monoexponential and there were no noticeable pathological changes observed using light microscopy. (2) During radiation pneumonitis, T2f and T2s were prolonged. This accompanied acute edematous changes and inflammatory cell infiltration. (3) Finally, during radiation fibrosis T1 shortened and collagen increased. We observed no significant correlation between relaxation time changes and water content changes throughout the 1-year time course.     

山莨菪碱对海水淹溺兔外周血单核细胞NF-κB表达的干预作用

目的：探讨山莨菪碱对海水淹溺后兔外周血中单核细胞核转录因子κB（NF-κB）的表达以及海水淹溺性肺水肿（PE-SVCD）治疗作用。方法：家兔气管切开后模拟海水淹溺造成急性肺损伤,于淹溺前（T1）,淹溺后15、30、60、120、240、480min（T2～T7）7个时间点采集外周血进行血气分析,并测定外周血炎症介质含量和单核细胞中NF-κB的淹溺前后表达变化,并采集肺组织。结果：海水淹溺致兔急性肺损伤各时间点肺组织中性粒细胞大量浸润,淹溺后外周血单核细胞NF-κB的表达开始增高,90 min后达到最高峰,而山莨菪碱可降低NF-κB以及炎症因子表达（P〈0.01）。结论：海水淹溺急性肺损伤可能与NF-κB高表达有关。山莨菪碱可降低NF-κB表达,减轻肺损伤程度。     

Quantitation of lung water by nuclear magnetic resonance imaging. A preliminary study

Pulmonary edema was produced in four anesthetized dogs by saline lavage. The animals were maintained by assisted ventilation with O2/halothane and examined by a nuclear magnetic resonance (NMR) 0.15T resistive-magnet imager. The distribution of edematous fluid was clearly observed. Image contrast increased with prolongation of the cycle time (TR). Tomographic maps of spin-lattice relaxation times (T1) of the lungs were calculated from the NMR images. Comparison of T1 values with gravimetric measurements of water content of lung samples showed significant correlation (r = .7, P less than .02, n = 12) suggesting a potential for in vivo lung water quantitation by NMR imaging. This in vivo correlation is qualitatively similar to the in vitro correlation. Accurate in vivo determinations of pulmonary T2 values may require respiratory gating.     

Effects of endotoxin lung injury on NMR T2 relaxation

The effects of endotoxin injury on lung NMR relaxation times (T₁, CPMG T₂, and Hahn decay constant (Hahn T₂)) were studied in excised unperfused rat lungs. Blinded histologic examination showed no clear-cut separation between endotoxin and control lungs. Morphometric lung tissue volume density and gravimetric lung water content did not differ significantly between the two groups. In contrast, the values of the fast, intermediate, and slow T₂ components, obtained by multiexponential analysis of the CPMG decay curve, increased markedly after endotoxin administration, with minimal overlap between endotoxin and control values. The response of Hahn T₂ was, in general, in the same direction as that of CPMG 7₂; however, Hahn T₂ may be more affected by measurement errors and may be less sensitive to the presence of lung injury. t₁ showed minimal changes after injury. The present data suggest that CPMG 7₂ measurements can consistently detect the presence of lung injury even when conventional histologic, morphometric, and gravimetric studies provide negative or equivocal results, and that the CMPG T₂ method is superior, in this respect, to the Hahn decay method. T₁ does not appear to be sensitive to lung injury in the absence of significant lung water accumulation.     

Pulmonary ventilation: dynamic MRI with inhalation of molecular oxygen

We have recently demonstrated a non-invasive technique to visualize pulmonary ventilation in humans with inhalation of molecular oxygen as a paramagnetic contrast agent. In the current study, T1 shortening of lung tissue by inhalation of oxygen was observed (P<0.001). The T1 values of lung tissue were also correlated with arterial blood oxygen pressure (PaO(2)) in a pig, resulting in excellent correlation (r(2)=0.997). Dynamic wash-in and wash-out MR ventilation images as well as dynamic wash-in wash-out signal intensity versus time curves were obtained. The mean wash-in decay constants were 26.8+/-10.5 s in the right lung, and 26.3+/-9.5 s in the left lung. The mean wash-out decay constants were 23.3+/-11.3 s in the right lung, and 20.8+/-10.5 s in the left lung. Dynamic assessment of pulmonary ventilation is feasible using oxygen-enhanced MR imaging, which could provide dynamic MR ventilation-perfusion imaging in combination with recently developed MR perfusion imaging technique, and thus a robust tool for the study of pulmonary physiology and pathophysiology.     

Nuclear magnetic resonance spectroscopy of acute and evolving pulmonary hemorrhage. An in vitro study

The proton NMR relaxation times of lung tissue were determined in a rabbit model of acute and evolving pulmonary hemorrhage (PH). Pure PH was simulated by injecting blood into a single lobe using endobronchial catheterization. In vitro spectroscopic measurements of T1 and T2 were made and total water content was determined on lung samples that were excised at regular intervals. T1 and T2 were markedly longer in lungs with acute PH than in normal lungs (T1: 818 +/- 44 vs. 643 +/- 4 msec; T2 164.0 +/- 16.3 vs. 88.1 +/- 3.4 msec). Within the first 24 hours, evolving PH was characterized by a rapid and progressive decrease in T1 (-50%) and T2 (-57%). Up to seven days after the instillation of blood, the T1 (450 +/- 43 msec) and T2 (69.7 +/- 1.9 msec) of lung with modeled PH remained below values of normal lung. The observed shortening of the relaxation times of lung disease with PH was closely paralleled by a decrease in tissue water content.     

高原胸部火器伤后TXB2和6-keto-PGF1α含量的变化及其意义

目的探讨高原胸部火器伤早期血浆及肺组织血栓素B2（TXB2）和6-酮-前列腺素F1α（6-keto-PGF1α）的变化及其意义。方法 18只体重相近（10～15 kg）的健康杂种犬,随机分成3组（每组6只）：平原伤前组、平原对照组和高原移居组,另外6只高原杂种犬作为高原世居组。平原对照组实验海拔高度为500 m,高原组实验海拔高度为3700 m。实验动物用3%戊巴比妥钠静脉麻醉（30 mg/kg）后,用0.44 g钢珠以400 m/s的初速度从右第6肋间射入,造成右胸贯通伤,伤后立即封闭伤口,安放胸腔闭式引流。各组分别在伤后2、4、6、8、12 h通过中心静脉插管抽取血标本,伤后12 h取双侧肺组织,检测血和肺组织内的TXB2和6-keto-PGF1α含量。结果各组伤后血浆6-keto-PGF1α和TXB2均明显升高,而TXB2和6-keto-PGF1α的比值仅高原移居组在伤后6 h开始有明显升高。各组伤侧肺组织的TXB2/6-keto-PGF1α比值都比平原伤前组明显增高,尤以高原移居组最为明显;但是,健侧肺组织TXB2/6-keto-PGF1α的比值仅高原移居组显著升高,其他组无显著差异。结论高原世居组和平原对照组在胸部火器伤后,肺组织水肿主要局限在伤侧;而高原移居组在胸部火器伤后早期,不论是伤侧还是健侧肺,均存在发生水肿的风险,在伤后应积极预防肺水肿的发生。     

间断缺氧习服大鼠血浆、肺组织血管内皮生长因子变化及意义

目的 探讨间断缺氧习服对在鼠血浆、肺组织血管内皮生长因子（VEGF）含量的影响,为进一步认识高原水肿发病及高原习服机理提供实验依据。方法 40只雄性Wistar大鼠分为常氧对照组、急性缺氧组和3组间断缺氧习服组（IHa、b、c）。急性缺氧组直接在低压舱中模拟海拔8000m缺氧4h,间断缺氧习服组分别在低压舱中模拟不同海拔高度及不同时间进行间断缺氧习服,每天4h,间断缺氧习服后的大鼠再进行急性缺氧（低压舱中模拟8000m,4h）。用酶标记免疫吸附测定法测定大鼠血浆VEGF水平,免疫组化方法测定肺组织VEGF表达。结果 缺氧大鼠血浆及肺组织VEGF较对照组明显升高,差异有非常显著性意义（P＜0．01）,以急性缺氧组升高明显（P＜0．01）;急性缺氧组肺组织有液体渗出及微血管内血球淤积现象;间断缺习服大鼠血浆及肺组织VEGF升高幅度较急性缺氧组明显降低,差异有显著性意义（P＜0．05）,而且随间断缺氧习服时间的延长,升高幅度呈下降趋势,肺组织液体渗出明显好转。结论 极度缺氧导致VEGF显著升高可能是血管通透性增加的重要原因;VEGF与高原肺水肿的发病及高原习服密切相关。     

NMR relaxation times in acute myocardial infarction: relative influence of changes in tissue water and fat content.

Tissue changes known to occur with acute myocardial infarction include increases in tissue water and lipid content. We sought to evaluate the relative contribution of alterations in tissue water and fat content to the changes of T1 and T2 relaxation times with infarction. Nine mongrel dogs underwent coronary artery occlusion for 6-12 h. T1 and T2 at 20 MHz and tissue water and fat content of normal and infarcted tissue were measured. Tissue water content, T1, and T2 were significantly greater in infarcted myocardium compared to normal (P less than 0.05). Tissue fat content, while not significantly different, increased linearly in infarcted samples as a function of duration of ischemia (r = 0.77). Despite this increase in fat content, only tissue water content was significantly linearly related to T1 (r = 0.97) and T2 (r = 0.91). Increases in T1 and T2 of infarcted tissue appeared to be most significantly influenced by changes in tissue water content. While total tissue fat content increased with duration of ischemia, it did not appear to significantly alter T1 or T2.     

Characteristics of extracellular sodium relaxation in perfused hearts with pathologic interventions.

Sodium spectroscopy and imaging sequences designed to emphasize fast T2 decay or the multiple quantum signal have previously demonstrated a high contrast between normal and pathologic tissue which may be due to changes in intracellular versus extracellular sodium distribution. Since alterations in the amount of signal with fast T2 decay have previously been shown to occur with changes in intracellular sodium content, this study investigated the fast T2 relaxation characteristics of extracellular sodium during pathologic interventions on nonsubmerged perfused rat hearts. T2 data on total sodium content were obtained while global ischemia (stopping all perfusate flow) and extracellular edema (due to long perfusion times) were induced in the heart. The data were fit to a biexponential, with Mf(T2f) the magnitude (time constant) of the fast component of decay. Mf increased significantly in both pathologies (to 319 +/- 26%, n = 3, of baseline for ischemia and to 527 +/- 284%, n = 3, of baseline for edema); the increase with edema was demonstrated to be due to extracellular sodium by intermittently perfusing the heart for a short period with shift reagent. When shift reagent was not used until the conclusion of the edema experiment, Mf increased to 169 +/- 35% of baseline, also due mainly to extracellular sodium. T2f did not exhibit any trends with these experiments, with values ranging from 1.7 to 5.5 ms. We believe that these results indicate that compartmental sodium content will most likely not be quantifiable in pathologic states in the heart with relaxation-based techniques. However, correlations between the pathologic state of the tissue and the sodium NMR signal obtained with pulse sequences or images that emphasize a particular aspect of relaxation may prove to be useful.     

Magnetic resonance imaging of hydrostatic pulmonary edema in isolated dog lungs: comparison with computed tomography

Magnetic resonance imaging (MRI) is considered inferior to computed tomography (CT) in the assessment of lung parenchyma, being hampered by low proton density, magnetic susceptibility effects, flow, and cardiac and respiratory motion. In this study the authors assessed the potential usefulness of MRI by comparing it with corresponding CT images of the lung in the absence of motion. They studied eight excised normal canine lung lobes inflated with oxygen before and after induction of pulmonary edema produced by intravascular infusion of saline at 30 cm H2O. T1, T2 and proton density weighted, 5-mm thick, gapped, multislice sequences were performed at 1.5 T. Magnetic resonance images were compared with corresponding 5-mm collimation CT scans at identical levels both before and after the induction of pulmonary edema. The MR and CT scans were assessed independently by two chest radiologists. In normal lung, there was equivalent visualization of vessels down to 1 mm and bronchi to 2 mm in diameter. T1 and proton density scans demonstrated lower spatial resolution but greater contrast than the corresponding CT images. In pulmonary edema both T1 and proton density sequences demonstrated peribronchial edema with greater contrast than CT. Air-space filling was equally well demonstrated by either technique. The authors conclude that, in motionless lung, MRI has lower spatial but greater contrast resolution than CT. It is potentially superior to CT in assessing focal and diffuse lung disease if cardiac and respiratory motion artifacts can be minimized or suppressed.     

Nuclear magnetic resonance relaxation in experimental brain edema: effects of water concentration, protein concentration, and temperature

Proton relaxation times T1 and T2 of macromolecular solutions, bovine brain tissues, and experimental cat brain edema tissues were studied as a function of water concentration, protein concentration, and temperature. A linear relation was found between the inverse of the weight fraction of tissue water and the spin-lattice relaxation rate, R1, based on a fast proton exchange model for relaxation. This correlation was also found for the spin-spin relaxation rate, R2, of gray matter samples and macromolecular solutions at low concentrations. Concentrated solutions of protein-water samples showed an enhanced relaxation due to viscosity effects. The T2 of white matter was considerably lengthened with elevated water concentration, but showed no straightforward relation with the total tissue water content. The relaxation times of all samples increased with temperature, supporting the assumption of fast proton exchange in the model for relaxation. This was not found for white matter, in which T2 decreased with increasing temperature, which indicated that intermediate or even slow exchange was present. The relation found between relaxation times and tissue water content can be used to predict the amount of and/or increase in tissue water due to water-elevating processes such as edema.