Tracking oxygen effects on MR signal in blood and skeletal muscle during hyperoxia exposure.

Blood and muscle T1 and T2 relaxivity was examined under normoxic (air; 20.8% O2) and hyperoxic (100% O2) conditions to determine whether the oxygenation state of blood in the large vessels and in the microcirculation can be monitored in vivo. The femoral artery/vein and the soleus and gastrocnemius muscles were examined in healthy human male volunteers. Arterial blood T1 decreased with hyperoxia, while venous blood T2 increased, due to increased dissolved O2 and decreased deoxyhemoglobin, respectively. A biexponential T2 model of muscle is proposed, where the short T2 component reflects primarily the intracellular and interstitial compartments (in fast exchange), and the long T2 reflects blood. In this model, the long T2 component increased with hyperoxia exposure. This was more evident in slow twitch (soleus) than in fast twitch (gastrocnemius) muscle. It is concluded that changes in the long T2 component reflect change in the microcirculation oxygenation state.     

Acute and repair stage characteristics of magnetic resonance relaxation times in oxygen-induced pulmonary edema

Proton magnetic relaxation times, T1 and T2, were determined for rat lungs exposed to 80% oxygen for a duration of 2 weeks. The transverse magnetization decay curve of the lung tissue was multiexponential. A linear combination of two decay curves with different T2 values fits the multiexponential decay suggesting that there are at least two different components of tissue water in the lung. Remarkable prolongation of T1 and T2 was demonstrated as lung injuries progressed in the acute stage of pulmonary edema. Both 1/T1 and 1/T2 were significantly correlated with 1/water content of the lung tissue. In the repair stage, T1 and T2 were significantly shortened. Shortening coincided with the spontaneous resolution of pulmonary edema. Relaxation rates showed no significant correlation with 1/water content in this stage. These results indicate that the physical state of water in the tissue is affected not only by the water content but also by the derangement of macromolecules in pulmonary edema. T2 was more sensitive than T1 for detecting pulmonary damage.     

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.     

Comparative measurement of regional blood flow, oxygen and glucose utilisation in soft tissue tumour of rabbit with positron imaging

The C15O2 and 15O2 steady state techniques have been used to quantitatively measure regional blood flow (RBF) and regional oxygen utilisation (ROU) in a rabbit tumour model. RBF values of 4.6 +/- 0.6 ml min/100 cc were measured for normal muscle tissue and 11.0 +/- 3.0 ml/min/100 cc for tumour surface. Corresponding values for ROU were 18.3 +/- 3.5 mumol/min/100 cc for normal tissue and 39.7 +/- 20.1 mumol/min/100 cc for tumour surface. 18F-2-fluoro-2-deoxy-D-glucose (2FDG) was used in the same tumour model to measure glucose metabolic rate. The values obtained were 4.3 +/- 2.1 mumol/min/100 cc for normal muscle tissue and 53.8 +/- 18.3 mumol/min/100 cc for tumour tissue. Tumour growth was followed with a series of measurements of blood flow, oxygen, and glucose metabolism at intervals of 1 week. Tumour-to-muscle ratios increased more rapidly with time for 2FDG than for oxygen utilisation and blood flow. The effect of radiation on tumour and normal tissue was followed by measurements of RBF and ROU. RBF values increased both in tumour and normal muscle tissue during radiation and decreased during one week after radiation. ROU-values decreased (30%) in tumour and increased (45%) in normal muscle tissue during radiation. Even at one week after radiation, ROU-values were 30% lower in tumour and 45% higher in normal muscle tissue than before radiation.     

Age-dependent variation of T1 and T2 relaxation times of adenocarcinoma in mice

The T1 and T2 values of adenocarcinoma EO 771 inoculated into the hind leg of mice are characterized and correlated with the histopathologic state of the tumor. Growth-dependent changes (indicated by a T1 of 630-910 msec and a T2 of 68-185 msec) can be separated into four characteristic phases. The increase in relaxation times in the early phases (A and B) is due to an increasing amount of viable tumor tissue relative to normal muscle tissue. In the later phases (C and D), a decline of the relaxation parameters is observed that is parallel to an increase in the fraction of necrotic tissue. By multiexponential analysis, two relaxation components (indicated by and, respectively) for T1 and T2 and the corresponding fractions alpha 1 and alpha 2 can be observed for both tumor and surrounding muscle tissue. A tissue criterion ("magnetic resonance fingerprint") is defined by a combination of these multiple parameters. This criterion allows separation of not only muscle and tumor tissue but also viable (early state) and necrotic (late state) tumor tissue.     

Osmotic effects on the T2 relaxation decay of in vivo muscle.

Saline solutions are commonly employed as a vehicle for drugs administered intramuscularly. In this study, in vivo measurements of spin-spin relaxation (T2) processes by magnetic resonance imaging (MRI) were performed to investigate the distribution of water in rat masseter muscle tissue after intramuscular injection of saline solutions of varying tonicity. Prior to saline injection, image-based T2 relaxation decay of muscle was monoexponential. After injection of saline, the T2 relaxation decay became multiexponential. Non-negative least squares (NNLS) analysis of the decay curves revealed two relaxation components: a fast component (T2 = 20-40 ms) and a slow component (T2 = 150-400 ms), which are assigned to intra- and extracellular water protons, respectively. Injection of hypertonic saline solutions significantly increased the extracellular water component in muscle tissue compared to isotonic saline solutions, an effect which lasted for more than 60 min. These findings suggest that MRI techniques may be useful to investigate the effect of hyper- or hypotonic solutions on muscle tissue in vivo.     

Simultaneous temperature and regional blood volume measurements in human muscle using an MRI fast diffusion technique

The thermal dependence of the translational diffusion coefficient and of the regional blood volume was investigated in vivo by using a special MR pulsed gradient technique with reduced sensitivity to bulk tissue motion. Measurements were done at 0.5 T, using a small gradient insert. The diffusion coefficient of muscle water was calibrated against thermocouple-measured temperature in vitro, both with the muscle fibers parallel and perpendicular to the diffusion gradient. The maximum muscle temperature variation obtained by percutaneous conduction was ?8.8 ± 1.6°C under cooling and +3.7 ± 1.6°C under heating, from basal state. Simultaneously the fractional regional blood volume decreased by a factor of 3.5 under cooling and increased by a factor of 2.7 under heating. Due to the interdependence of microcirculation and tissue temperature, this technique may be used to follow heat production or deposition in living tissue (muscle exercise, electromagnetic irradiation, etc.).     

Detecting microcirculatory changes in blood oxygen state with steady-state free precession imaging.

Recently, it has been demonstrated that oxygen-weighted images of whole blood can be obtained with steady-state methods. In this article, based on computational and experimental models, we investigate the potential for employing this technique to monitor oxygen changes in microcirculation. Results show that oxygen-sensitive images of rabbit kidney and muscle may be obtained at high signal-to-noise ratio within a few seconds. The results also show that in steady-state free precession imaging, in addition to the exchange mechanism that generates oxygen contrast in blood, there are additional mechanisms that provide oxygen-sensitive contrast in microcirculation.     

高原施工人员不同海拔高度和居住时间氧疗前后微循环变化

 目的 探讨高原施工人员不同海拔高度、不同居住时间氧疗前后微循环的变化。方法 选取2000名高原施工人员,在不同海拔,监测并分析3、7、15、30、60、90 d、1年吸氧前后微循环变化。结果 吸氧组微循环血流、血管形态、红细胞聚集、管襻形态、襻顶淤血、襻周出血、乳头下血管丛等变化明显优于不吸氧组 。吸氧前血液流态积分显著降低,前后比较差异有统计学意义(χ²=6.48,P<0.05),管周状态差异有统计学意义(χ²=4.36,P<0.05),积分显著增高,差异有统计学意义(P<0.05),海拔5 000 m以上吸氧后较吸氧前管周状态积分增高非常显著(P<0.01)。其他积分和总积分虽有增高或降低,均无统计学意义。结论 微循环变化明显好于对照组,尤其是血管清晰度、血液流态流速、血管变异、红细胞聚集等方面。     

Assessment of T1 and T2* effects in vivo and ex vivo using iron oxide nanoparticles in steady state--dependence on blood volume and water exchange.

Accurate knowledge of the relationship between contrast agent concentration and tissue relaxation is a critical requirement for quantitative assessment of tissue perfusion using contrast-enhanced MRI. In the present study, using a pig model, the relationship between steady-state blood concentration levels of an iron oxide nanoparticle with a hydrated diameter of 12 nm (NC100150 Injection) and changes in the transverse and longitudinal relaxation rates (1/T2* and 1/T1, respectively) in blood, muscle, and renal cortex was investigated at 1.5 T. Ex vivo measurements of 1/T2* and 1/T1 were additionally performed in whole pig blood spiked with different concentrations of the iron oxide nanoparticle. In renal cortex and muscle, 1/T2* increased linearly with contrast agent concentration with slopes of 101 +/-22 s(-1)mM(-1) and 6.5 +/-0.9 s(-1)mM(-1) (mean +/- SD), respectively. In blood, 1/T2* increased as a quadratic function of contrast agent concentration, with different quadratic terms in the ex vivo vs. the in vivo experiments. In vivo, 1/T1 in blood increased linearly with contrast agent concentration, with a slope (T1-relaxivity) of 13.9 +/- 0.9 s(-1)mM(-1). The achievable increase in 1/T1 in renal cortex and muscle was limited by the rate of water exchange between the intra- and extravascular compartments and the 1/T1-curves were well described by a two-compartment water exchange limited relaxation model.     

18F-氟赤式硝基咪唑肿瘤乏氧显像实验研究

目的 探讨18F-氟赤式硝基咪唑(FETNIM)在肿瘤乏氧诊断中的应用价值.方法 30只SPCA-1人肺腺癌荷瘤BALB/c裸鼠采用随机数字表法分为A和B 2组(鼠数分别为16和14只).尾静脉注射37 MBq18F-FETNIM后A组分别于注射后0.5,1,2,3 h处死裸鼠,取血液、肺、心、肝、脾、肾、肿瘤等组织测量质量,用γ计数仪测定放射性计数,计算每克组织百分注射剂量率(%ID/g);B组用PO2微电极测量肿瘤组织内乏氧情况.结果 18F-FETNIM在肾中代谢最高,在脂肪和骨骼中代谢较低,肿瘤/正常组织的放射性比值较高,且随时间而增加,2 h达最高,肿瘤/血液放射性比值为1.69±0.37,肿瘤/肌肉放射性比值为1.57±0.47.HE染色显示瘤内有大量的乏氧坏死组织.组织内PO2微电极测量示肿瘤内均有乏氧,肿瘤内PO,1.1～27.7 mm Hg(1 mm Hg=0.133 kPa).结论 18F-FETNIM在荷瘤裸鼠体内具有较低的外周代谢,脂溶性较低,能被肿瘤乏氧组织摄取,可用于肿瘤乏氧诊断.     

Oxygenation and hematocrit dependence of transverse relaxation rates of blood at 3T.

Knowledge of the transverse relaxation rates R2 and R2* of blood is relevant for quantitative assessment of functional MRI (fMRI) results, including calibration of blood oxygenation and measurement of tissue oxygen extraction fractions (OEFs). In a temperature controlled circulation system, these rates were measured for blood in vitro at 3T under conditions akin to the physiological state. Single spin echo (SE) and gradient echo (GRE) sequences were used to determine R2 and R2*, respectively. Both rates varied quadratically with deoxygenation, and changes in R2* were found to be due predominantly to changes in R2. These data were used to estimate intravascular blood oxygenation level dependent (BOLD) contributions during visual activation. Due to the large R2* in venous blood, intravascular SE BOLD signal changes were larger than GRE effects at echo times above 30 ms. When including extravascular effects to estimate the total BOLD effect, GRE BOLD dominated due to the large tissue volume fraction.     

Factors controlling T2 mapping from partially spoiled SSFP sequence: optimization for skeletal muscle characterization

A fast and robust methodology for in vivo T(2) mapping is presented. The approach is based on the partially spoiled steady state free precession technique recently proposed by Bieri et al. (Magn Reson Med 2011). The accuracy of this method was demonstrated in simulations and phantom experiments. Variations in skeletal muscle T(2) relaxation time have been correlated with cell damage and inflammatory response. Nonetheless, the lack of easily implementable, fast, accurate and reproducible methods has hampered the adoption of T(2) measurement as a noninvasive tool for skeletal muscle characterization. The applicability of the partially spoiled steady state free precession method for tissue characterization in muscle disease is illustrated in this work by several examples. Quantitative MRI, in particular T(2) mapping based on partially spoiled steady state free precession acquisitions, might provide objective markers of muscle damage and degenerative changes, and an alternative to serial muscle biopsies.     

BOLD magnetic resonance imaging of skeletal muscle

Blood-oxygen-level-dependent (BOLD) imaging was a concept introduced in 1990 for evaluating brain activation. The method relies on magnetic resonance imaging (MRI) contrast resulting from changes in the microvascular ratio of oxyhaemoglobin (oxyHb) to deoxyhaemoglobin (deoxyHb). OxyHb is diamagnetic, whereas deoxyHb is paramagnetic, which produces a local bulk magnetic susceptibility effect and subsequent MRI signal change. The changes are typically observed in T(2)*-weighted functional MRI scans. However, there has recently been interest in BOLD as a way to evaluate microcirculation of any normal or diseased tissue. This review focuses on the application of BOLD imaging in the understanding of normal and diseased skeletal muscle. In addition we present new findings showing the possible application of BOLD imaging with hyperoxia for evaluating skeletal muscle physiology.     

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.     

T1 relaxation time at 0.2 Tesla for monitoring regional hyperthermia: feasibility study in muscle and adipose tissue.

The purpose of this study was to characterize T(1), particularly in the hyperthermia temperature range (ca. 37-44 degrees C), in order to control regional hyperthermia with MR monitoring using 0.2 Tesla, and to improve T(1) mapping. A single-slice and a new multislice "T One by Multiple Read-Out Pulses" (TOMROP) pulse sequence were used for fast T(1) mapping in a clinical MRI hyperthermia hybrid system. Temporal stability, temperature sensitivity, and reversibility of T(1) were investigated in a polyamidacryl gel phantom and in samples of muscle and adipose tissues from turkey and pig, and verified in patients. In the gel phantom a high linear correlation between T(1) and temperature (R(2) = 0.97) was observed. In muscle and adipose tissue, T(1) and temperature had a linear relationship below a breakpoint of 43 degrees C. Above this breakpoint muscle tissue showed irreversible tissue changes; these effects were not visible in adipose tissue. The ex vivo results were confirmed in vivo under clinical conditions. T(1) mapping allows the characterization of hyperthermia-related tissue response in healthy tissue. T(1), in combination with fast mapping, is suitable for controlling regional hyperthermia at 0.2 T within the hybrid system.     

Quantitative T*(2) and T'(2) maps during reversible focal cerebral ischemia in rats: separation of blood oxygenation from nonsusceptibility-based contributions.

Quantitative imaging contrast is evaluated which allows the selective measurement of the blood oxygenation state during cerebral ischemia within a multiparametric imaging study on rats. In a first step, the ambiguities arising in T*(2)-weighted images due to T*(2) heterogeneity are eliminated by calculating T*(2) maps. Then, 1/T'(2) maps are calculated according to 1/T'(2) = 1/T*(2) - 1/T(2) to eliminate nonsusceptibility-induced changes of 1/T*(2) after the induction of stroke. This is of particular importance in the presence of vasogenic edema. The changes Delta(1/T'(2)) after the onset of ischemia selectively quantify the variations of the deoxyhemoglobin content during the development of the infarct. The presented results are not available from conventionally recorded parameters of a stroke study and, together with perfusion-weighted images, form a powerful combination to analyze the oxygen consumption and the metabolism of the tissue. Magn Reson Med 42:1027-1032, 1999.     

Achilles tendon and paratendon microcirculation in midportion and insertional tendinopathy in athletes

BACKGROUND: Neovascularisation can be detected qualitatively by Power Doppler in Achilles tendinopathy. Quantitative data regarding tendon microcirculation have not been established and may be substantial. PURPOSE: To assess the microcirculation of the Achilles tendon and the paratendon in healthy volunteers as well as in athletes with either midportion or insertional tendinopathy. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: In 66 physically active volunteers, parameters of Achilles tendon and paratendon microcirculation, such as tissue oxygen saturation, relative postcapillary venous filling pressures, and microcirculatory blood flow, were determined at rest at 2-mm and 8-mm tissue depths. Forty-one patients never had Achilles pain (25 men, 27 +/- 8 years), 14 patients had insertional pain (7 men, 29 +/- 8 years), and 11 patients had midportion tendinopathy (7 men, 38 +/- 13 years, not significant). RESULTS: Achilles tendon diameter 2 cm and 6 cm proximal to the insertion was increased in symptomatic tendons. Compared with the uninvolved opposite tendon, deep microcirculatory blood flow was significantly elevated at insertional (160 +/- 79 vs 132 +/- 42, P < .05) as well as in midportion tendinopathy (150 +/- 74 vs 119 +/- 34, P < .05). The microcirculation in the uninvolved opposite tendon and the normal athlete controls were not significantly different from each other (132 +/- 42 insertional asymptomatic vs 119 +/- 34 mid-portion vs 120 +/- 48 healthy tendon). Insertional paratendon deep microcirculatory flow was elevated in all groups, whereas tissue oxygen saturation and relative postcapillary venous filling pressures were not significantly different. CONCLUSION: Microcirculatory blood flow is significantly elevated at the point of pain in insertional and midportion tendinopathy. Postcapillary venous filling pressures are increased at both the midportion Achilles tendon and the midportion paratendon, whereas tissue oxygen saturation is not different among the studied groups. We found no evidence of an abnormal microcirculation of the asymptomatic limb in Achilles tendinopathy.     

T(2) + measurement during acute cerebral ischemia by Carr-Purcell MRI at 4T.

Metabolic and structural changes occur in brain tissue within minutes of ischemia. The adiabatic multi-echo (Carr-Purcell) localization pulse sequence LASER has shown promise in detecting tissue contrast changes within the first hour of ischemia. The purpose of this initial study was to combine the LASER localization sequence with fast 3D echo-planar imaging (EPI) to quantify the regional apparent transverse relaxation (T(2) (dagger)) in a rabbit model of acute embolic ischemia at 4 Tesla. Carr-Purcell T(2) (dagger)-weighted images were acquired at 7 different echo-times and used to estimate T(2) (dagger) in both cortex and striatum. In ischemic tissue identified by 2,3,5-triphenyltetrazolium chloride (TTC) staining, the T(2) (dagger) increased by approximately 31% after 1 hour of ischemia and remained elevated until study completion at 4 h of ischemia. Lesion volume, defined as the number of pixels with T(2) (dagger) greater than 90 ms, increased by 40% between 1 and 4 h after induction of ischemia. Carr-Purcell LASER-EPI T(2) (dagger)-weighted images show promise in detecting early tissue changes in focal cerebral ischemia.     

Alterations of the proton-T2 time in relaxed skeletal muscle induced by passive extremity flexions

PURPOSE: To demonstrate reciprocal changes of the apparent proton-T2 time in the biceps and triceps due to passive contraction and extension of the muscle fibers. MATERIALS AND METHODS: The contraction state of the upper arm muscles of six healthy volunteers was passively changed by alternating the forearm position between the straight-arm position and an elbow flexion of 90 degrees. The relaxation of the muscle during passive contraction and extension was measured with the use of muscle electromyography (EMG) experiments. Spin-echo (SE) MRI with increasing echo times (TEs) of 12-90 msec was used to acquire the averaged signal decay of the segmented biceps and triceps. The apparent T2 was deduced using monoexponential least-square fitting. RESULTS: The median T2 alterations in biceps and triceps among all volunteers were found to be 1.2 and -1.3 msec in the straight and bent forearm positions, respectively. The confidence intervals (0.5 to 1.7 msec in biceps, and -2.6 to -1.1 msec in triceps) clearly indicate that proton-T2 in MR images is significantly (P < 0.05) prolonged with muscle contraction. CONCLUSION: The observed increase of the proton-T2 time was correlated with a passive contraction of skeletal muscle fibers. This passive effect can be attributed to changes in the intracellular water mobility corresponding to the well-known "active" T2 increase that occurs after stimulation of muscle.