The effect of haemosiderosis and blood transfusions on the T2 relaxation time and 1/T2 relaxation rate of liver tissue.

Patients with chronic anaemia need repeated blood transfusions, which eventually lead to iron overload. The excess iron from blood transfusions is deposited in the reticuloendothelial system and in the parenchymal cells of the liver, spleen and other organs. Cellular damage is likely to occur when iron overload in the liver is pronounced. Liver biopsy is still necessary to evaluate the degree of haemosiderosis or haemochromatosis. To avoid this invasive procedure, methods have been sought to determine the concentration of iron in liver tissue and to estimate the effect of the treatment of haemosiderosis or haemochromatosis. In this MRI study, the T2 relaxation time and the 1/T2 relaxation rate of liver were determined in 23 patients who had undergone repeated blood transfusions for chronic anaemia. The first 60 transfusions had the greatest influence on the measured T2 relaxation time, with T2 relaxation time decreasing as haemosiderosis progresses. The 1/T2 relaxation rate increases significantly in a linear fashion when the number of blood transfusions increases up to 60. After 60 transfusions the influence of additional blood transfusions on the T2 value was minimal; the same response, although in reverse, was seen in the 1/T2 relaxation rate curve. One possible explanation for this may be that the MR system could detect the effect of only a limited amount of iron excess and any concentration over this limit gives a very short T2 relaxation time and a very weak signal from the liver, which is overwhelmed by background noise. However, in mild and moderate haemosiderosis caused by blood transfusions, T2 relaxation time and 1/T2 relaxation rate reflect iron accumulation in liver tissue.     

Magnetic starch microspheres, biodistribution and biotransformation. A new organ-specific contrast agent for magnetic resonance imaging

The biodistribution and elimination of magnetic starch microspheres (MSM) were studied qualitatively and quantitatively by radioiron tracer studies and relaxation time measurements. One hour after injection of MSM (1 mg/kg of Fe), 85% +/- 5% of the dose was accumulated in the liver and 6.5% +/- 1.3% [corrected] in the spleen. The hepatic clearance led to 50% reduction in the T2 relaxation time of liver tissue. This T2 effect was halved after 24 hours and T2 reversed to baseline value within 5 days after injection. The radioiron was gradually cleared from the liver with a t1/2 of 4 to 5 days. Six weeks after injection of MSM, 72% +/- 7% of the radioiron dose was detected in the circulation in a nonsuperparamagnetic form associated with the erythrocytes. The results indicate a redistribution of iron from the liver and spleen via the erythroid bone marrow to the erythrocytes after injection of MSM.     

Dextran magnetite as a liver contrast agent

The superparamagnetic particle dextran magnetite was studied as a liver tumor contrast agent for magnetic resonance imaging (MRI). The effects of dextran magnetite on the longitudinal (T1) and transverse (T2) relaxation times in liver, spleen, and an implanted rat liver tumor were measured at 0.47 T (IBM/Bruker PC-20 relaxometer) over the dose range of 23 to 69 mumol Fe/kg. Dextran magnetite substantially reduced the T2 of the liver and spleen, but not of the tumor, thereby providing a basis for improved tumor imaging. The T1 of the tumor was not affected following injection of dextran magnetite in the dose range studied, while the spleen T1 was reduced substantially more than the T1 of the liver. Histological studies using the iron reaction for Prussian blue clearly showed dextran magnetite in the liver and spleen, but not in the tumor. While dextran magnetite was sequestered in macrophages in both liver and spleen, the distribution in the liver was more diffuse (70 microns average particle separation) than that in the spleen (25 microns separation). The lack of a T1 effect in the liver is consistent with the fact that a majority of the water in the tissue cannot diffuse to the relaxational centers on the time scale of the liver's intrinsic T1 (280 ms). In the spleen, however, the dextran magnetite is more densely packed in the red pulp allowing a significant fraction of the water to be relaxed by a T1 mechanism. Spin-echo images of the implanted tumor (mammary adenocarcinoma. R3230AC) in the livers of Fischer 344 rats were obtained at 0.50 T (Siemens Magnetom). The tumor-to-liver contrast was improved for both T1 and T2-weighted spin-echo images after intravenous injection of the dextran magnetite contrast agent. The contrast determined from these images agreed with that predicted by the measured T1 and the T2 (Hahn spin-echo) values. In addition, gradient-echo T2-weighted images with good contrast were obtained in a much shorter imaging time than was needed for T2-weighted spin-echo images. These results demonstrate that the MRI contrast enhancement observed with dextran magnetite is based on its selective uptake and distribution in the macrophages in the liver and spleen and that this agent has substantial potential as a superparamagnetic MR contrast agent.     

RES-specific imaging of the liver and spleen with iron oxide particles designed for blood pool MR-angiography.

The purpose of this study was to determine the dependency of liver- and spleen-enhancement on particle size and dose of bolus-injectable iron oxides designed for blood-pool MR-angiography (MRA). The superparamagnetic iron oxide SHU 555 A [particle size 65 nm (group 1)] and three derivatives designed for blood-pool MRA (groups 2-4) with smaller hydrodynamic diameters (46/33/21 nm) were i.v. injected in New Zealand White rabbits at doses of 10, 20, or 40 micromol Fe/kg bw. MRI was performed before, 2, and 24 hours after contrast application using T1-weighted SE and T2-weighted TSE sequences. In addition splenic tissue was harvested post mortem and scanned ex vivo. All iron oxides significantly decreased the SI of liver and spleen in T1- and T2-weighted images at 2 and 24 hours after application of contrast media (P < 0.01). The signal intensity was inversely related to the dose applied. Decreasing particle size resulted in a lower signal enhancement in liver and spleen. However, ultra-small superparamagnetic iron oxides suited for blood-pool MRA (USPIOs, group 4) still revealed a significant signal enhancement in the liver and spleen even 24 hours after contrast application (< - 60%, 40 micromol Fe/kg bw). They might thus be used for comprehensive abdominal studies including contrast enhanced MR-angiography and RES-specific imaging.     

Superparamagnetic iron oxide: pharmacokinetics and toxicity

The pharmacokinetics (distribution, metabolism, bioavailability, excretion) and toxicity (acute and subacute toxicity, mutagenicity) of a superparamagnetic iron oxide preparation (AMI-25), currently used in clinical trials, were evaluated by 59Fe radiotracer studies, measurements of relaxation times, the ability to reverse iron deficiency anemia, histologic examination, and laboratory parameters. One hour after administration of AMI-25 to rats (18 mumol Fe/kg; 1 mg Fe/kg), 82.6 +/- 0.3% of the administered dose was sequestered in the liver and 6.2 +/- 7.6% in the spleen. Peak concentrations of 59Fe were found in liver after 2 hr and in the spleen after 4 hr. 59Fe slowly cleared from liver (half-life, 3 days) and spleen (half-life, 4 days) and was incorporated into hemoglobin of erythrocytes in a time-dependent fashion. The half-time of the T2 effect on liver and spleen (24-48 hr) was shorter than the 59Fe clearance, indicating metabolism of AMI-25 into other forms of iron. IV administration of AMI-25 (30 mg Fe/kg) corrected iron-deficiency anemia and showed bioavailability similar to that of commercially available IV iron preparations within 7 days. No acute or subacute toxic effects were detected by histologic or serologic studies in rats or beagle dogs who received a total of 3000 mumol Fe/kg, 150 times the dose proposed for MR imaging of the liver. Our results indicate that AMI-25 is a fully biocompatible potential contrast agent for MR.     

Tissue distribution and magnetic resonance spin lattice relaxation effects of gadolinium-DTPA

Gadolinium-DTPA complex (Gd-DTPA) is a potential clinical magnetic resonance (MR) contrast agent that enhances images primarily by decreasing spin-lattice relaxation time (T1) in tissues in which it localizes. This study was designed to determine the immediate tissue distribution of intravenously administered Gd-DTPA in selected organs of interest as a function of administered dose and tissue Gd-DTPA concentration. An intravenous bolus of Gd-DTPA with a tracer quantity of Gd-153 was administered to three groups of rabbits at the following doses: 0.01 mM/kg (n = 6); 0.05 mM/kg (n = 6); 0.10 mM/kg (n = 6). A control group received sham injections. Five minutes after Gd-DTPA was administered, all animals were killed; samples of serum, lung, heart, kidney, liver, and spleen were analyzed in a 0.25 T MR spectrometer to measure T1, and then in a gamma well counter to determine tissue concentration of Gd-DTPA. Tissue distribution (per cent dose/tissue weight in g) at five minutes after injection was proportionally constant over the range of doses given. Tissue concentration varied linearly with injected dose (r greater than 0.98 for all tissues). Relaxation rate (1/T1) varied linearly with injected dose and with tissue Gd-DTPA concentration (r greater than 0.97 for all tissues). The order of tissue relaxation rate response to a given dose was: kidney greater than serum greater than lung greater than heart greater than liver greater than spleen. We conclude that because of its extracellular distribution and linear relaxation rate versus concentration relationship, Gd-DTPA enhancement in MR images may be a good marker of relative organ perfusion.     

Relaxation effects of clustered particles.

Relations between spatial distribution of superparamagnetic iron oxide (SPIO) particles and the image contrast caused by SPIO were investigated. Actual clustering pattern of particles was measured in the liver and spleen of animals using intravital laser confocal microscopy. SPIO-doped phantoms with and without Sephadex beads were made to simulate these patterns, and relaxation parameters were measured using a 1.5-T clinical scanner. Finally, these results were compared to clinical image data using SPIO particulate agent. Intravital microscopy indicated that the clustering of latex beads was more predominant in hepatic Kupffer cells than in splenic macrophages (P < 0.001). Phantoms without Sephadex beads showed an approximately linear increase of 1/T1 (R1), 1/T2 (R2) and 1/T2* (R2*) values with increasing SPIO concentration. However, with Sephadex beads, R1 and R2 showed little change with increasing SPIO concentration, while R2* showed the same linear increase with SPIO. Also, the R2* values were higher with Sephadex beads. These results were consistent with the clinical imaging data, where signal reduction was significantly smaller in the spleen (-0.4% +/- 27.4%) than in the liver (50.4% +/- 16.8%, P < 0.00001) on T2*-weighted images, but the reduction in the spleen (47.2% +/- 16.1%) was equivalent to the liver (38.8% +/- 26.0%) on T2-weighted images.     

MR relaxation times and iron content of thalassemic spleens: an in vitro study

To determine the relationship between MR relaxation times and the iron content of the spleens in patients with thalassemia, we measured these parameters at 0.19 and 1.18 T in 19 thalassemic spleen specimens in vitro. The correlation was best between iron content and the dependence between the interecho interval and the 1/T2 (T2 relaxation rate) at 1.18 T(r = .9361, p less than .001). No statistically significant correlation was found between T1 and iron content at either field strength. The variation of the 1/T2 with interecho interval may be useful for measuring iron content in vivo. It supports the theory that the T2 relaxation of iron deposits occurs via cellular field gradients produced by intralysosomal granules of hemosiderin.     

Comparison between signal-to-noise ratio,liver-to-muscle ratio,and 1/T2 for the noninvasive assessment of liver iron content by MRI

PURPOSE: To compare different MRI-derived parameters, i.e., liver signal-to-noise ratio (LSNR), liver-to-muscle ratio (LMR) and liver transversal relaxation rate (R2), in terms of their correlation with the ex vivo determined iron content in an experimental model of liver iron overload. MATERIALS AND METHODS: Multi-echo spin echo (SE) images of the liver were acquired at 4.7 T from a group of 33 male wistar rats subjected to a high iron content diet for feeding periods ranging from 2 to 50 days. Liver transversal relaxation time, liver signal-to-noise ratio, and liver-to-muscle ratio were measured over the same region of interest in order to get a direct comparison between these parameters. After MRI experiments, the rats were sacrificed and the liver iron content was measured ex vivo by atomic absorption spectroscopy. RESULTS: The iron content is better correlated to the LSNR than to the other parameters (LMR, R2). CONCLUSION: The finding that liver signal-to-noise ratio is better correlated to the iron content than the liver T2 relaxation rate is relevant for clinical applications of MRI because a T2 determination is more time-consuming, both for acquisition and postprocessing of images, than a simple SNR determination.     

MR imaging relaxation times of abdominal and pelvic tissues measured in vivo at 3.0 T: preliminary results

PURPOSE: To measure T1 and T2 relaxation times of normal human abdominal and pelvic tissues and lumbar vertebral bone marrow at 3.0 T. MATERIALS AND METHODS: Relaxation time was measured in six healthy volunteers with an inversion-recovery method and different inversion times and a multiple spin-echo (SE) technique with different echo times to measure T1 and T2, respectively. Six images were acquired during one breath hold with a half-Fourier acquisition single-shot fast SE sequence. Signal intensities in regions of interest were fit to theoretical curves. Measurements were performed at 1.5 and 3.0 T. Relaxation times at 1.5 T were compared with those reported in the literature by using a one-sample t test. Differences in mean relaxation time between 1.5 and 3.0 T were analyzed with a two-sample paired t test. RESULTS: Relaxation times (mean +/- SD) at 3.0 T are reported for kidney cortex (T1, 1,142 msec +/- 154; T2, 76 msec +/- 7), kidney medulla (T1, 1,545 msec +/- 142; T2, 81 msec +/- 8), liver (T1, 809 msec +/- 71; T2, 34 msec +/- 4), spleen (T1, 1,328 msec +/- 31; T2, 61 msec +/- 9), pancreas (T1, 725 msec +/- 71; T2, 43 msec +/- 7), paravertebral muscle (T1, 898 msec +/- 33; T2, 29 msec +/- 4), bone marrow in L4 vertebra (T1, 586 msec +/- 73; T2, 49 msec +/- 4), subcutaneous fat (T1, 382 msec +/- 13; T2, 68 msec +/- 4), prostate (T1, 1,597 msec +/- 42; T2, 74 msec +/- 9), myometrium (T1, 1,514 msec +/- 156; T2, 79 msec +/- 10), endometrium (T1, 1,453 msec +/- 123; T2, 59 msec +/- 1), and cervix (T1, 1,616 msec +/- 61; T2, 83 msec +/- 7). On average, T1 relaxation times were 21% longer (P <.05) for kidney cortex, liver, and spleen and T2 relaxation times were 8% shorter (P <.05) for liver, spleen, and fat at 3.0 T; however, the fractional change in T1 and T2 relaxation times varied greatly with the organ. At 1.5 T, no significant differences (P >.05) in T1 relaxation time between the results of this study and the results of other studies for liver, kidney, spleen, and muscle tissue were found. CONCLUSION: T1 relaxation times are generally higher and T2 relaxation times are generally lower at 3.0 T than at 1.5 T, but the magnitude of change varies greatly in different tissues.     

超顺磁性氧化铁（SPIO）对比剂肝脾MR成像的比较研究

目的 比较两种超顺磁性氧化铁（superparamagnetic iron oxide,SPIO)对比剂,Ferumoxides及SHU－555A在肝脾MR成像中的效应。材料与方法 36例已知为肝转移癌患者于SPIO造影前后进行T2WI快速自旋回波成像（T2WI TSE）及T1WI梯度回波快去速相位成像（T1WI FLASH）。扫描伪为1．0T MR机。18例患者行Ferumoxides增强后90分钟进行MR成像;另18例行SHU－55A快速团柱增强,注药后即刻、30秒及480秒行T1WI FLASH成像,10分钟行T2WI TSE成像。测量肝脾、肝转移癌SPIO增强前后的信号强度（signal intensity,SI),计算两种SPIO对比剂在肝脾、肝转移癌增强前后SI变化的百分比（percentage signal intensity change,PSIC)及病灶肝脏对比噪声比（lesion-to-liver contrast-to-noise ratio,CNR)及其变化（ΔCNR）。结果 在T2WI TSE图像上,两种SPIO对比剂造成的肝实质SI下降无显著性差异（P＞0．05）。Ferumoxides引的脾信号下降显著大于SHU－555A（P＜0．05）。两种SPIO对比剂均导致肝实转移癌SNR显著增高。T1WI FLASH图像上,两种对比剂均可导致延迟像上肝脏SI的轻度下降及肝转移癌CNR下降,两者肝脏SIC之间无显著性差异。T1WI上两种对比剂均可导致脾脏SI显著升高,两者脾脏PSIC之间无显著性差异（P＞0．05）。结论 两种SPIO在肝脏的TI及T2增强效应相似,而脾脏的T2增强效应,Ferumoxides强于SHU－555A。     

Enhancement effects of a hepatocyte receptor—specific MR contrast agent in an animal model

The enhancement characteristics of the liver and spleen produced by a hepatocyte-specific magnetic resonance imaging agent, an arabinogalactan-coated ultrasmall superparamagnetic iron oxide derivative, BMS 180550, were evaluated. Both heavily T1- and T2-weighted sequences were used. Imaging was performed in the farm pig model, as a function of contrast agent concentration (5, 10, and 20 μmol of iron per kilogram) and delay (immediate, 0.5, 2.5, 5.0, 7.5, and 9.0 hours) after bolus injection of BMS 180550. BMS 180550 provided excellent contrast enhancement characteristics by producing marked positive enhancement with T1-weighted sequences and marked negative enhancement with T2-weighted sequences. The T1-weighted enhancement immediately after contrast agent injection was of greater magnitude in the spleen (329% ± 83) than in the liver (66% ± 16). Postcontrast negative enhancement with T2-weighted sequences was largely hepatocyte specific at 5 and 10 μmol/kg but was also seen within the spleen at 20 μmol/kg. The authors discuss the possible mechanisms that produce these changes and conclude that 10 μmol/kg BMS 180550 is near the optimum dose for maximizing the enhancement properties of this agent with all sequences in the farm pig.     

Evaluation of different models of experimentally induced liver cirrhosis for MRI research with correlation to histopathologic findings

RATIONALE AND OBJECTIVES: Three models of experimentally induced liver cirrhosis were evaluated for MRI research on chronic liver disease. The influence of different histopathologic changes in liver fibrosis and cirrhosis on relaxation times and signal intensities was studied in vitro and in vivo. METHODS: Liver fibrosis and cirrhosis in rats was induced by oral or subcutaneous administration of carbon tetrachloride (CCl4) or by thioacetamide (TAA) in drinking water. On histology, the degree of liver fibrosis and cirrhosis, fatty infiltration, iron accumulation, and inflammatory changes were measured semiquantitatively. The amount of connective tissue was quantitatively determined by morphometry. The results were correlated with T1 and T2 relaxation times and signal intensities of the liver studied in vitro by relaxometry and in vivo by MRI. RESULTS: In both groups with CCl4 administration, histology revealed different degrees of liver fibrosis and cirrhosis. Subcutaneous injection of CCl4 also resulted in increased fatty infiltration. On the contrary, TAA produced complete liver cirrhosis in all animals. Overall, there was a good correlation between the liver T2 relaxation time and the amount of connective tissue in liver fibrosis and cirrhosis. However, the degree of liver fibrosis and cirrhosis was also strongly correlated with the degree of inflammatory changes. In the group with CCl4 administration, there was a good correlation between the fatty infiltration and the T1 relaxation time, as well as with the liver signal intensity on the T1-weighted gradient echo sequence. An increased iron accumulation was also correlated with the degree of liver fibrosis/cirrhosis; however, there was no significant influence of the iron on relaxation times or signal intensities. CONCLUSIONS: The TAA model is easier to perform and more reliable in liver cirrhosis induction than the CCl4 models. Although there is a positive correlation between the T2 relaxation times and the degree of liver fibrosis/cirrhosis, this probably results from the associated inflammatory changes and is not caused by the increased amount of connective tissue.     

Long-term imaging effects in rat liver after a single injection of an iron oxide nanoparticle based MR contrast agent

PURPOSE: To investigate the duration of liver R2* enhancement and pharmacokinetics following administration of an iron oxide nanoparticle in a rat model. MATERIALS AND METHODS: Rats were injected with 0, 1, 2, or 5 mg Fe/kg of NC100150 Injection, and quantitative in vivo 1/T2* liver measurements were obtained between 1 and 133 days after injection. The concentration of NC100150 Injection was determined by relaxometry methods in ex vivo rat liver homogenate. RESULTS: At all dose levels, 1/T2* remained greater than control values up to 63 days after injection. In the highest dose group, 1/T2* was above control levels during the entire 133 day time-course investigated. There were no quantifiable amounts of NC100150 Injection present 63 days after injection in any of the dose groups. The half-life of NC100150 Injection in rat liver was dose dependent. For the lowest dose group, the degradation of the particles could be defined by a mono-exponential function with a half-life of eight days. For the 2 and 5 mg Fe/kg dose groups, the degradation was bi-exponential with a fast initial decay of seven to eight days followed by a slow terminal decay of 43-46 days. CONCLUSION: NC100150 Injection exhibits prolonged 1/T2* enhancement in rat liver. The liver enhancement persisted at time points when the concentration of iron oxide particles present in the liver was below method detection limits. The prolonged 1/T2* enhancement is likely a result of the particle breakdown products and the induction of ferritin and hemosiderin with increasing iron cores/loading factors.     

Superparamagnetic iron oxide: clinical time-response study.

Superparamagnetic iron oxide (AMI 25) is a promising new contrast agent for imaging the reticuloendothelial-system. Iron oxide crystals possess a large magnetic susceptibility and enhance proton relaxation rates, especially transverse relaxation (T2). In order to guide the clinical utilization of this contrast media we analyzed 4 patients with malignant lesions of the liver before and after slow intravenous administration (20 mumol Fe/kg) of AMI 25. We performed two magnetic resonance (MR) sequences at different times using a 0.35 T magnet. MR signal-to-noise ratio (SNR) of the reticuloendothelial system (particularly the liver SNR) decrease promptly. The maximum decrease in SNR (67-72% for the liver, 46-65% for the spleen, 23-41% for the bone marrow) is observed 3 h after injection (P less than 0.01). However, except the peak of contrast enhancement in T1-weighted sequences of splenic tissue, the curve describes a plateau within 30 min and 6 h, allowing a delay between injection and imaging. T2-weighted sequences give a greater contrast-to-noise ratio (CNR) by adding the spontaneous tumor contrast to the effect yielded by AMI 25. These results suggest that images must be acquired between 1 and 6 h after intravenous administration of superparamagnetic iron oxide.     

Ferritin-induced relaxation in tissues: an in vitro study

PURPOSE: To study in vitro the proton relaxation induced in tissues by ferritin, the iron-storing protein of mammals. MATERIALS AND METHODS: Nuclear magnetic relaxation dispersion (NMRD) profiles of liver and spleen from control and iron-overloaded mice are compared with NMRD profiles of ferritin and Fercayl-a ferritin-like akaganeite particle-in aqueous solutions or in 1% agarose gel. RESULTS: The relaxation of water protons induced by ferritin and Fercayl in 1% agarose gel is comparable with the relaxation of aqueous solutions of the same compounds, but slower than the relaxation of liver and spleen. The gel is not a good model of tissues containing ferritin. The longitudinal NMRD profiles of control and iron-overloaded liver and spleen are almost identical: ferritin accumulation has only a slight effect on longitudinal relaxation. The transverse NMRD profiles of liver and spleen tissues are linear, but the slope of the linear regression is larger for iron-loaded organs than for control ones, which is a consequence of a higher ferritin concentration in the former. However, the correlation between the slope of the transverse NMRD profiles and the iron concentration is not very good, probably because transverse relaxation is modified by the clustering of ferritin in cells. CONCLUSION: It could be difficult to develop a general technique for the accurate quantification of ferritin-bound iron by nuclear magnetic resonance or magnetic resonance imaging.     

Experimental study of embolo-hyperthermia for treatment of liver tumor--induction heating to ferromagnetic particles injected into tumor tissue

Hepatic arterial embolization was performed on VX2 liver tumor of rabbit with subsequent induction heating to the tumor. Prior to the heating, iron particle suspension was injected into tumor tissue as a target of induction heating (500 KHZ, 9 KW). The temperatures of the tumor and liver parenchyma were measured with fluoroptic thermometer. Elevation of the tumor temperature during initial heating for 6 minutes were well correlated to the dose of iron particles injected; 1.4 degrees C with 1 g, 3.0 degrees C with 2 g, and 4.9 degrees C with 3 g. The temperature of liver parenchyma were below 39 degrees C even with 3 g injection.     

Enhancement efficacy of magnetic starch microspheres (MSM) in conventional spin-echo and turbo spin-echo sequences at 0.5 T and 1.5 T

The efficacy of the superparamagnetic contrast agent magnetic starch microspheres (MSM) was evaluated in vitro by NMR relaxometry and in vivo by MR imaging using T2-weighted spin-echo (SE) and turbo spin-echo (TSE) sequences at 0.5 T and 1.5 T in 60 normal rats who received MSM in doses of 10–50 μmol/kg. MR imaging was performed using T2-weighted SE and TSE sequences. The relaxation rates 1/T1 and 1/T2 for liver and spleen increased linearly with MSM concentrations up to 30 μmol/kg body weight, and approached almost constant levels for higher doses. The slopes in the linear part of the 1/T2 diagram were 0.62 Hz ± 0.03 for the liver and 0.51 Hz ± 0.06 × kg/μmol for the spleen. On all T2-weighted sequences at 0.5 T and 1.5 T, liver signal-to-noise ratio (SNR) decreased by a factor of 2-3 already at the lowest dose of 10 μmol/kg. SNR values of TSE sequences exceeded values for SE sequences by 50–80%. The SNR decrease was not significantly different between SE and TSE sequences. Our results show that MSM is well suited as a T2 contrast agent at both magnetic field strengths when using conventional SE and fast TSE sequences.     

Organ-specific effects of oxygen and carbogen gas inhalation on tissue longitudinal relaxation times.

Molecular oxygen has been previously shown to shorten longitudinal relaxation time (T1) in the spleen and renal cortex, but not in the liver or fat. In this study, the magnitude and temporal evolution of this effect were investigated. Medical air, oxygen, and carbogen (95% oxygen/5% CO2) were administered sequentially in 16 healthy volunteers. T1 maps were acquired using spoiled gradient echo sequences (TR=3.5 ms, TE=0.9 ms, alpha=2 degrees/8 degrees/17 degrees) with six acquisitions on air, 12 on oxygen, 12 on carbogen, and six to 12 back on air. Mean T1 values and change in relaxation rate were compared between each phase of gas inhalation in the liver, spleen, skeletal muscle, renal cortex, and fat by one-way analysis of variance. Oxygen-induced T1-shortening occurred in the liver in fasted subjects (P<0.001) but not in non-fasted subjects (P=0.244). T1-shortening in spleen and renal cortex (both P<0.001) were greater than previously reported. Carbogen induced conflicting responses in different organs, suggesting a complex relationship with organ vasculature. Shortening of tissue T1 by oxygen is more pronounced and more complex than previously recognized. The effect may be useful as a biomarker of arterial flow and oxygen delivery to vascular beds.     

Effect of oxygen inhalation on relaxation times in various tissues

The effect of the oxygen inhalation on relaxation times was evaluated in various tissues, including the myocardium, liver, spleen, skeletal muscle, subcutaneous fat, bone marrow, and arterial blood, with a [¹H]MR system. Statistically significant decrease of T1 relaxation times was observed in the myocardium, spleen, and arterial blood after inhalation of 100% oxygen, whereas no significant change was observed in liver, skeletal muscle, subcutaneous fat, or bone marrow. The T2 relaxation time of these tissues did not differ significantly between before and after inhalation of the oxygen. These results indicate that [¹H]MRI can be used to evaluate changes with oxygen inhalation and that the effect of the oxygen inhalation on T1 relaxation time is different among various tissues.