19F Magnetic resonance imaging of perfluorooctanoic acid encapsulated in liposome for biodistribution measurement

The tissue distribution of perfluorooctanoic acid (PFOA), which is known to show unique biological responses, has been visualized in female mice by (19)F magnetic resonance imaging (MRI) incorporated with the recent advances in microimaging technique. The chemical shift selected fast spin-echo method was applied to acquire in vivo (19)F MR images of PFOA. The in vivo T(1) and T(2) relaxation times of PFOA were proven to be extremely short, which were 140 (+/- 20) ms and 6.3 (+/- 2.2) ms, respectively. To acquire the in vivo (19)F MR images of PFOA, it was necessary to optimize the parameters of signal selection and echo train length. The chemical shift selection was effectively performed by using the (19)F NMR signal of CF(3) group of PFOA without the signal overlapping because the chemical shift difference between the CF(3) and neighbor signals reaches to 14 kHz. The most optimal echo train length to obtain (19)F images efficiently was determined so that the maximum echo time (TE) value in the fast spin-echo sequence was comparable to the in vivo T(2) value. By optimizing these parameters, the in vivo (19)F MR image of PFOA was enabled to obtain efficiently in 12 minutes. As a result, the time course of the accumulation of PFOA into the mouse liver was clearly pursued in the (19)F MR images. Thus, it was concluded that the (19)F MRI becomes the effective method toward the future pharmacological and toxicological studies of perfluorocarboxilic acids.     

Relaxation and diffusion of perfluorocarbon gas mixtures with oxygen for lung MRI

We report measurements of free diffusivity D(0) and relaxation times T(1) and T(2) for pure C(2)F(6) and C(3)F(8) and their mixtures with oxygen. A simplified relaxation theory is presented and used to fit the data. The results enable spatially localized relaxation time measurements to determine the local gas concentration in lung MR images, so the free diffusivity D(0) is then known. Comparison of the measured diffusion to D(0) will express the extent of diffusion restriction and allow the local surface-to-volume ratio to be found.     

Magic sandwich echo relaxation mapping of anisotropic systems

The main objective of this article was (i) to refocus the residual dipolar and quadrupolar interactions in anisotropic tissues employing magic sandwich echo (MSE) imaging and to compare the results with that of conventional spin-echo (SE) imaging, and (ii) to quantify MSE relaxation and dispersion characteristics in bovine Achilles tendon and compare with spin-lattice relaxation time constant in the rotating frame (T(1rho)). Magic sandwich echo weighted images are approximately 75-100% higher in signal-to-noise ratio than the corresponding T(2)-weighted images. Magic sandwich echo relaxation times varied from 13+/-2 to 19+/-3 ms (mean+/-S.D.), depending upon the structural location of tendon. T(2) relaxation times only varied from 4+/-1 to 10+/-3 ms (mean+/-S.D.) on the same corresponding locations. Magic sandwich echo provides approximately 100% enhancement in relaxation times compared to T(2). Preliminary results based on bovine Achilles tendon and cartilage specimens suggest that the MSE technique has potential for refocusing residual dipolar as well as quadrupolar interactions in anisotropic systems and yields higher intensities than conventional SE imaging as well as T(1rho)-encoded imaging, especially at low-burst pulse amplitudes (250 and 500 Hz).     

Flow and oxygenation dependent (FLOOD) contrast MR imaging to monitor the response of rat tumors to carbogen breathing

Gradient recalled echo (GRE) images are sensitive to both paramagnetic deoxyhaemoglobin concentration (via T2*) and flow (via T1*). Large GRE signal intensity increases have been observed in subcutaneous tumors during carbogen (5% carbon dioxide, 95% oxygen) breathing. We term this combined effect flow and oxygenation-dependent (FLOOD) contrast. We have now used both spin echo (SE) and GRE images to evaluate how changes in relaxation times and flow contribute to image intensity contrast changes. T1-weighted images, with and without outer slice suppression, and calculated T2, T2* and "flow" maps, were obtained for subcutaneous GH3 prolactinomas in rats during air and carbogen breathing. T1-weighted images showed bright features that increased in size, intensity and number with carbogen breathing. H&E stained histological sections confirmed them to be large blood vessels. Apparent T1 and T2 images were fairly homogeneous with average relaxation times of 850 ms and 37 ms, respectively, during air breathing, with increases of 2% for T1 and 11% for T2 during carbogen breathing. The apparent T2* over all tumors was very heterogeneous, with values between 9 and 23 ms and localized increases of up to 75% during carbogen breathing. Synthesised "flow" maps also showed heterogeneity, and regions of maximum increase in flow did not always coincide with maximum increases in T2*. Carbogen breathing caused a threefold increase in arterial rat blood PaO2, and typically a 50% increase in tumor blood volume as measured by 51Cr-labelled RBC uptake. The T2* increase is therefore due to a decrease in blood deoxyhaemoglobin concentration with the magnitude of the FLOOD response being determined by the vascular density and responsiveness to blood flow modifiers. FLOOD contrast may therefore be of value in assessing the magnitude and heterogeneity of response of individual tumors to blood flow modifiers for both chemotherapy, antiangiogenesis therapy in particular, and radiotherapy.     

Spin-echo fluorine magnetic resonance imaging at 2 T: in vivo spatial distribution of halothane in the rabbit head

Spin-echo 19F magnetic resonance imaging was performed at 2.0 T to explore the in vivo spatial distribution of halothane in the rabbit head. Because the halothane concentration is low in vivo, and because the measured relaxation times of the 19F resonance peak for halothane were T1 approximately equal to 1.0 sec and T2 approximately equal to 3.5-65 msec, 1-3-h imaging times were required (TR = 1 sec, TE = 9 msec) in order to obtain adequate images with a 64 X 256 raw data matrix and a 20-mm slice thickness. With this technique, halothane was primarily detected in lipophilic regions of the rabbit head, but little or no halothane was observed in brain tissue. Because T2 was shorter in brain tissue than in surrounding fat, a shorter TE than we could obtain is needed for optimal spin-echo imaging of brain halothane.     

Two-exponential analysis of spin-spin proton relaxation times in MR imaging using surface coils

Proton relaxation time measurements were performed on a standard whole body MR imager operating at 1.5 T using a conventional surface coil of the manufacturer. A combined CP/CPMG multiecho, multislice sequence was used for the T1 and T2 relaxation time measurements. Two repetition times of 2000 ms (30 echoes) and 600 ms (2 echoes) with 180 degrees-pulse intervals of 2 tau = 22 ms were interleaved in this sequence. A two-exponential T2 analysis of each pixel of the spin-echo images was computed in a case of an acoustic neurinoma. The two-exponential images show a "short" component (T2S) due to white and gray matter and a "long" component (T2S) due to the cerebrospinal fluid. In the fatty tissue two components with T2S = 35 +/- 3 ms and T2L = 164 +/- 7 ms were measured. Comparing with Gd-DTPA imaging the relaxation time images show a clear differentiation of vital tumor tissue and cerebrospinal fluid.     

In vivo relaxation times of gray matter and white matter in spinal cord

In vivo relaxation times and relative spin densities of gray matter (GM) and white matter (WM) of rat spinal cord were measured. Inductively coupled implanted RF coil was used to improve the signal-to-noise ratio required for making these measurements. The estimated relaxation times (in milliseconds) are: T1(GM) = 1021+/-93, T2(GM) = 64+/-3.4, T1(WM) = 1089+/-126, and T2(WM) = 79+/-6.9. The estimated relative spin densities are: rho(GM) = (60+/-2.3)% and rho(WM) = (40+/-2.1)%. The T1 values of GM and white matter are not statistically different. However, the differences in T2 values and spin densities of GM and WM are statistically significant. These in vivo measurements indicate that the observed contrast between GM and WM in spinal cord MR images mainly arises from the differences in the spin density.     

Magnetic resonance imaging of the uterus at an ultra low (0.02 T) magnetic field.

In vivo pelvic imaging of 39 women and in vitro relaxation time measurements of four uterine specimens were performed using an ultra low field (0.02 T) MRI unit. Average T1 times measured in vitro at 37 degrees C for the myometrium and endometrium were 206 ms (SD 47 ms) and 389 ms (SD 21 ms), respectively. Corresponding T2 times were 95 ms (SD 20 ms) and 167 ms (SD 13 ms). The proton relaxation of almost all myometrial specimens proved to be biexponential, but of all endometrial specimens was monoexponential. Contrast measurements between endometrium versus myometrium and myometrium versus the junctional zone were performed after imaging 18 volunteer women using different pulse sequence parameters. Normal uterine structures were optimally demonstrated by SE 700/70. Relatively short repetition times could be used, because spin-lattice relaxation times were short at the low magnetic field. Consequently, the short repetition times allowed averaging of four excitations to create adequate images within an acceptable scanning time. In addition to T2-weighted images a T1-weighted inversion recovery sequence with a short inversion time of 50 ms (IR 1000/50/40) adequately differentiated the three uterine zones. Although pathologic lesions of the uterus including leiomyomas, anomalies and carcinomas were well demonstrated, especially with the T2-weighted spin echo pulse sequence, further investigations are needed to evaluate the optimal technique for ultra low field MR imaging of uterine tumors.     

Fast and precise T1 imaging using a TOMROP sequence

Proton spin-lattice (T1) relaxation time images were computed from a data set of 32 gradient-echo images acquired with a fast TOMROP (T One by Multiple Read Out Pulses) sequence using a standard whole-body MR imager operating at 64 MHz. The data acquisition and analysis method which permits accurate pixel-by-pixel estimation of T1 relaxation times is described. As an example, the T1 parameter image of a human brain is shown demonstrating an excellent image quality. For white and gray brain matter, the measured longitudinal relaxation processes are adequately described by a single-component least-squares fit, while more than one proton component has to be considered for fatty tissue. A quantitative analysis yielded T1 values of 547 +/- 36 msec and 944 +/- 73 msec for white and gray matter, respectively.     

Ex vivo magnetic resonance imaging of rat spinal cord at 9.4 T

The magnetic resonance (MR) properties of the rat spinal cord were characterized at the T9 level with ex vivo experiments performed at 9.4 T. The inherent endogenous contrast parameters, proton density (PD), longitudinal and transverse relaxation times T1 and T2, and magnetization transfer ratio (MTR) were measured separately for the grey matter (GM) and white matter (WM). Analysis of the measurements indicated that these tissues have statistically different proton densities with means PD(GM)=54.8+/-2.5% versus PD(WM)=45.2+/-2.4%, and different T1 values with means T1GM=2.28+/-0.23 s versus T1WM=1.97+/-0.21 s. The corresponding values for T2 were T2GM=31.8+/-4.9 ms versus T2WM=29.5+/-4.9 ms, and the difference was insignificant. The difference between MTR(GM)=31.2+/-6.1% and MTR(WM)=33.1+/-5.9% was also insignificant. These results collectively suggest that PD and T1 are the two most important parameters that determine the observed contrast on spinal cord images acquired at 9.4 T. Therefore, in MR imaging studies of spinal cord at this field strength, these parameters need to be considered not only in optimizing the protocols but also in signal enhancement strategies involving exogenous contrast agents.     

Investigation of microenvironmental factors influencing the longitudinal relaxation times of drugs and other compounds

The aim of this study was to investigate the microenvironmental factors likely to influence the longitudinal relaxation time of MR visible drugs or compounds in vivo at 1.5 T. The relative influence that viscosity, albumin and paramagnetic contrast agent concentrations have on the observed longitudinal relaxation times of three 19F MR detectable drugs and compounds have been investigated. Our data show that for 5-fluorouracil, flucloxacillin and tetrafluorosuccinic acid-containing phantoms, the presence of albumin at normal physiological concentrations will have relaxation effects of the same order of magnitude as that of a commonly clinically administered contrast agent, gadolinium diethylenetriamine pentaacetic acid. The contribution of viscosity is shown, in the examples studied here, to be of minor importance, contributing less than 6.5% to the observed relaxation effects. It is also demonstrated that in the presence of competitive binding of other ligands for common binding sites on albumin, the 19F longitudinal relaxation time of 5-fluorouracil can increase by up to 340% from its value in the absence of the competing ligand. The relevance of the findings to in vivo studies is discussed.     

Assessment of scanner performance and normalization of estimated relaxation rate values

The purpose of this study was to develop and test a method for the assessment of Magnetic Resonance (MR) scanner performance suitable for routine brain MR studies and for normalization of calculated relaxation times. We hypothesized that regular monitoring of machine performance changes could provide a helpful normalization tool for calculating tissue MR parameters, thus contributing to support their use for longitudinal and comparative studies of both normal and diseased tissues.The method is based on the acquisition of phantom images during routine brain studies with standard spin-echo sequences. MR phantom and brain tissue parameters were used to assess the influence of machine related changes on relaxation parameter estimates. Experimental results showed that scanner performance may affect relaxation rate estimates. Phantom and in vivo results indicate that the correction method yields a reduction in variability of estimated phantom R1 values up to 29% and of R1 for different brain structures up to 17%. These findings support the validity of using brain coil phantoms for routine system monitoring and correction of tissue relaxation rates.     

Nuclear magnetic resonance study of iron overload in liver tissue

Whole-tissue and homogenized samples of human liver were studied in a NMR spectrometer, T1 and T2 relaxation times were measured as a function of added inorganic or organic iron. When inorganic iron (Fe+3) was added, pronounced T1 and T2 shortening was noted. However, when organic iron, in the form of ferritin, was added, the amount of T1 and T2 relaxation enhancement was much reduced for the same amount of added iron. The in vitro ferritin results model the situation found in clinical studies of hemochromatosis. Only in cases of severe iron overload were significant decreases in relaxation times observed. The T2 relaxation time was the more reliable indicator of excessive levels of iron in the liver. The large range of T1 and T2 values encountered in normal volunteers precludes the use of MR to quantitatively measure iron levels in the liver. The T1 and T2 relaxation times measured at intervals for one individual tend to fluctuate as well, making the use of MR to follow the course of treatment of iron overload disorders unreliable.     

Oxygen-induced changes in longitudinal relaxation times in skeletal muscle

The objective was to measure the effect of 100% oxygen inhalation on T1 relaxation times in skeletal muscle. Healthy volunteers were scanned using three different MRI protocols while breathing medical air and 100% oxygen. Measurements of T1 were made from regions of interest (ROIs) within various skeletal muscle groups. Dynamic data of subjects breathing a sequence of air-oxygen-air allowed the calculation of characteristic wash-in and -out times for dissolved oxygen in muscle. Contrary to previous findings, a statistically significant decrease in T1 in skeletal muscle was observed due to oxygen inhalation. We report approximate baseline characteristic values for the response of skeletal muscle to oxygen inhalation. This measurement may provide new biomarkers for evaluation of oxygen delivery and consumption in normal and diseased skeletal muscle.     

MRI image plane nonuniformity in evaluation of ferrous sulphate dosimeter gel (FeGel) by means of T1-relaxation time

MR image nonuniformity can vary significantly with the spin-echo pulse sequence repetition time. When MR images with different nonuniformity shapes are used in a T1-calculation the resulting T1-image becomes nonuniform. As shown in this work the uniformity TR-dependence of the spin-echo pulse sequence is a critical property for T1 measurements in general and for ferrous sulfate dosimeter gel (FeGel) applications in particular. The purpose was to study the characteristics of the MR image plane nonuniformity in FeGel evaluation. This included studies of the possibility of decreasing nonuniformities by selecting uniformity optimized repetition times, studies of the transmitted and received RF-fields and studies of the effectiveness of the correction methods background subtraction and quotient correction. A pronounced MR image nonuniformity variation with repetition and T1 relaxation time was observed, and was found to originate from nonuniform RF-transmission in combination with the inherent differences in T1 relaxation for different repetition times. The T1 calculation itself, the uniformity optimized repetition times, nor none of the correction methods studied could sufficiently correct the nonuniformities observed in the T1 images. The nonuniformities were found to vary considerably less with inversion time for the inversion-recovery pulse sequence, than with repetition time for the spin-echo pulse sequence, resulting in considerably lower T1 image nonuniformity levels.     

Alterations in MR relaxation of normal canine gallbladder bile during fasting

The correlation between the concentration and proton relaxation of bile was studied by examining sequential changes in the MR image appearance and relaxation times of gallbladder bile during a 24-h fasting period in dogs. Bile relaxation times computed from images showed progressive shortening during the first 4–8 h of fasting: T₁ decreased from 500–900 ms to 250–400 ms and T₂ from 130–190 ms to 70–100 ms at 0.15 T. Similar in vitro results at 0.47 T were obtained on aspirated bile samples. Relaxation times of gallbladder bile remained longer than those of the liver, and we conclude that in general the gallbladder will appear less intense than the liver on T₁-weighted images (with short enough TE) and more intense on T₂-weighted images regardless of the bile concentration. The liver/gallbladder contrast may reverse in a normal subject during fasting for pulse sequences combining both T₁ and T₂ effects, which may be explored for the possible visual detection of abnormal gallbladder function on an image.     

Study of molecular dynamics and cross relaxation in tetramethylammonium hexafluorophosphate (CH(3))(4)NPF(6) by (1)H and (19)F NMR

(CH(3))(4)NPF(6) is studied by NMR measurements to understand the internal motions and cross relaxation mechanism between the heterogeneous nuclei. The spin lattice relaxation times (T(1)) are measured for (1)H and (19)F nuclei, at three (11.4, 16.1 and 21.34 MHz) Larmor frequencies in the temperature range 350-50K and (1)H NMR second moment measurements at 7 MHz in the temperature range 300-100K employing home made pulsed and wide-line NMR spectrometers. (1)H NMR results are attributed to the simultaneous reorientations of both methyl and tetramethylammonium groups and motional parameters are evaluated. (19)F NMR results are attributed to cross relaxation between proton and fluorine and motional parameters for the PF(6) group reorientation are evaluated.     

The effects of dissolved oxygen upon amide proton relaxation and chemical shift in a perdeuterated protein

The effects of dissolved molecular oxygen upon amide proton ((1)H(N)) longitudinal and transverse relaxation rates and chemical shifts were studied for a small protein domain, the second type 2 module of fibronectin ((2)F2)-isotopically enriched to 99% (2)H, 98% (15)N. Longitudinal relaxation rate enhancements, R(O(2))((1)H(N)), of individual backbone (1)H(N) nuclei varied up to 14 fold between a degassed and oxygenated (1 bar) solution, indicating that the oxygen distribution within the protein is inhomogeneous. On average, smaller relaxation rate enhancements were observed for (1)H(N) nuclei associated with the core of the protein compared to (1)H(N) nuclei closer to the surface, suggesting restricted oxygen accessibility to some regions. In agreement with an O(2)-(1)H(N) hyperfine interaction in the extreme narrowing limit, the (1)H(N) transverse relaxation rates showed no significant change, up to an oxygen pressure of 9.5 bar (the maximum pressure used in this study). For most (1)H(N) resonances, small deltadelta(O(2))((1)H(N)) hyperfine chemical shifts could be detected between oxygen pressures of 1 bar and 9.5 bar.     

Initial in vivo rodent sodium and proton MR imaging at 21.1 T

The first in vivo sodium and proton magnetic resonance (MR) images and localized spectra of rodents were attained using the wide bore (105 mm) high resolution 21.1-T magnet, built and operated at the National High Magnetic Field Laboratory (Tallahassee, FL, USA). Head images of normal mice (C57BL/6J) and Fisher rats (∼250 g) were acquired with custom designed radiofrequency probes at frequencies of 237/900 MHz for sodium and proton, respectively. Sodium MR imaging resolutions of ∼0.125 μl for mouse and rat heads were achieved by using a 3D back-projection pulse sequence. A gain in SNR of ∼3 for sodium and ∼2 times for proton were found relative to corresponding MR images acquired at 9.4 T. 3D Fast Low Angle Shot (FLASH) proton mouse images (50×50×50 μm³) were acquired in 90 min and corresponding rat images (100×100×100 μm³) within a total time of 120 min. Both in vivo large rodent MR imaging and localized spectroscopy at the extremely high field of 21.1 T are feasible and demonstrate improved resolution and sensitivity valuable for structural and functional brain analysis.     

Recurrent hepatocellular carcinoma versus radiation-induced hepatic injury: differential diagnosis with MR imaging

The objective of this study was to assess the value of MR imaging in the differentiation between a recurrent hepatocellular carcinoma (HCC) and a radiation-induced hepatic injury. Nine male patients with suspected recurrence after radiotherapy for HCC underwent T(2)-, T(1)-weighted imaging and Gd-DTPA enhanced dynamic studies. T(2) relaxation times, signal intensity ratios in T(1)-weighted images (WI) and the relative enhancement of the dynamic study were calculated. Recurrent tumors and the irradiated area showed similar image characteristics: hypointense in T(1)-WI and hyperintense in T(2)-WI. T(2) values and signal intensity ratios in the T(1)-WI were not significantly different. In the gadolinium-enhanced dynamic study, a recurrent HCC showed early enhancement, followed by a rapid washout. However, the irradiated liver parenchyma showed hyperintensity from an early phase, and contrast enhancement tended to be more prominent and prolonged at the end of the dynamic studies. The characteristic findings of the dynamic MR study enable us to distinguish between a recurrent HCC and a radiation-induced hepatic injury.