In vivo 19F spin relaxation and localized spectroscopy of fluoxetine in human brain

Fluorine-19 NMR spectroscopy was used to monitor the anti-depressant drug fluoxetine (and its metabolite norfluoxetine) in vivo in human brain. A quadrature birdcage head coil, developed for operation at 60.1 MHz, yielded a signal from the head 2 to 4 times stronger than for surface coils. It was used to measure the in vivo ¹⁹F spin-lattice relaxation time (T₁) of fluoxetine for five patients by the inversion-recovery technique. The individual T₁s varied from 149 to 386 ms, which was attributed in part to interindividual differences based on the reproducibility of a phantom T₁. The individual T₁ correlated weakly with approximate brain concentration. A lower limit of 3 to 4 ms was found for the spin-spin relaxation time from line width measurements. Low resolution 4-dimensional spectroscopic imaging confirmed that the single in vivo ¹⁹F resonance for fluoxetine arose primarily from brain. The spectrum of a cerebral hemisphere (in formalin) obtained at autopsy from a patient on 40 mg/day of fluoxetine for 19 weeks was comparable with that seen for patients in vivo. The in vivo signal arose about equally from fluoxetine and the active me tabolite norfluoxetine, as demonstrated by the in vitro ¹⁹F NMR spectrum of the lipophilic extract of a small section of brain. In virto quantitation of frozen samples from three brain regions yielded combined fluoxetine/norfluoxetine concentrations of 12.3 to 18.6 μ/ml, which is higher than typically determined in vivo, and suggests that the fluorinated drugs may not be 100% visible in vivo.     

Time and temperature dependence of MR parameters during thermal coagulation of ex vivo rabbit muscle

Detailed measurements of the T₁-weighted, T₂-weighted, and MT-weighted signal were performed for ex vivo muscle samples heated to various temperatures for different times. Consistent, monotonic increases in signal intensity were observed with progressive thermal coagulation, corresponding to an increase in T₂ relaxation time and an increase in MT-weighted signal for temperatures above 60°C. The relationship for T₁ relaxation was more complex, showing a decrease in T₁ relaxation from 40 to 60°C and an increase above 60°C. These techniques provide a more direct measure of tissue thermal coagulation than that provided by MR thermometry and suggest MR imaging strategies for the optimization and monitoring of thermal coagulation therapy protocols that create thermal damage in target tissues.     

Contrast at high field: Relaxation times,magnetization transfer and phase in the rat brain at 16.4 T

As field strength increases, the magnetic resonance imaging contrast parameters like relaxation times, magnetization transfer or image phase change, causing variations in contrast and signal‐to‐noise ratio. To obtain reliable data for these parameters at 16.4 T, high‐resolution measurements of the relaxation times T₁, T₂ and T₂*, as well as of the magnetization transfer ratio and the local frequency in the rat brain were performed. Tissue‐specific values were obtained for up to 17 brain structures to assess image contrast. The measured parameters were compared to those found at different field strengths to estimate contrast and signal behavior at increasing field. T₁ values were relatively long with (2272 ± 113) ms in cortex and (2073 ± 97) ms in white matter, but did not show a tendency to converge, leading to an almost linear increase in signal‐to‐noise ratio and still growing contrast‐to‐noise ratio. T₂ was short with (25 ± 2) ms in cortex and (20 ± 1) ms in white matter. Magnetization transfer effects increase by around 25% compared to published 4.7 T data, which leads to improved contrast. The image phase, as novel and high‐field specific contrast mechanism, is shown to obtain good contrast in deep brain regions with increasing signal‐to‐noise ratio up to high field strengths. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

MR measurement of relative water content and multicomponent T2 relaxation in human breast

MR techniques providing accurate measurement of relative volumetric water content and multicomponent T₂ relaxation times from a large volume of interest, have been implemented for characterization of breast tissue in vivo. In a sequence of 20-s breath-holds, data are obtained from much of the breast volume while suppressing signal from the chest wall and torso. Relative water content of each breast is calculated from one-dimensional fat and water profiles obtained using a hybrid two-point Dixon method (TE/TR=17/5000 ms). Multicomponent T₂ relaxation measurements are calculated from T₂ decay curves obtained using a CPMG train of rectangular pulses (TE/TR=8/5000 ms, 140 echoes) preceded by saturation pulses to localize longitudinal magnetization spatially. These techniques, validated in phantoms and human volunteers, are suitable for quantitative study of breast tissue in vivo, and in particular to investigate the potential role of MR for assessment of breast cancer risk.     

Anomalous Transverse Relaxation in 1H Spectroscopy in Human Brain at 4 Tesla

Longitudinal (T₁) and apparent transverse relaxation times (T₂) of choline-containing compounds (Cho), creatine/phospho-creatine (Cr/PCr), and N-acetyl aspartate (NAA) were measured in vivo in human brain at 4 Tesla. Measurements were performed using a water suppressed stimulated echo pulse sequence with complete outside volume presaturation to improve volume localization at short echo times. T₁-values of Cho (1.2 ± 0.1 s), Cr (1.6 ± 0.3 s), and NAA (1.6 ± 0.2 s) at 4 Tesla in occipital brain were only slightly larger than those reported in the literature at 1.5 Tesla. Thus, TR will not adversely affect the expected enhancement of signal-to-noise at 4 Tesla. Surprisingly, apparent T₂-values of Cho (142 ± 34 ms), Cr (140 ± 13 ms), and NAA (185 ± 24 ms) at 4 Tesla were significantly smaller than those at 1.5 Tesla and further decreased when increasing the mixing interval TM. Potential contributing factors, such as diffusion in local susceptibility related gradients, dipolar relaxation due to intracellular paramagnetic substances and motion effects are discussed. The results suggest that short echo time spectroscopy is advantageous to maintain signal to noise at 4 Tesla.     

Quantitative in vivo tissue sodium concentration maps: The effects of biexponential relaxation

The biexponential relaxation behavior of the sodium nucleus affects the accuracy of quantitative measurement of in vivo tissue sodium concentration (TSC). Theoretical analysis and in vivo experimental results are used to demonstrate the extent of the large bias in the measured TSC that arises when the relaxation behavior in vivo differs significantly from that of the calibration standards which is when a significant fraction of the total sodium signal decays with a relaxation time much shorter than the echo time (TE) used for imaging. This bias can be as large as 20% for measurements of TSC in a normal rat brain with TE = 2 ms. Our findings indicate that shortening the echo time (TE < 0.5 ms) by projection imaging is a reliable means of obtaining accurate in vivo estimates for TSC using MR.     

Origins of the ultrashort‐T2 1H NMR signals in myelinated nerve: A direct measure of myelin content?

Recently developed MRI techniques have enabled clinical imaging of short‐lived ¹H NMR signals with T₂ < 1 ms. Using these techniques, novel signal enhancement has been observed in myelinated tissues, although the source of this enhancement has not been identified. Herein, we report studies of the nature and origins of ultrashort T₂ (uT₂) signals (50 μs < T₂ < 1 ms) from amphibian and mammalian myelinated nerves. NMR measurements and comparisons with myelin phantoms and expected myelin components indicate that these uT₂ signals arise predominantly from methylene ¹H on/in the myelin membranes, which suggests that direct measurement of uT₂ signals can be used as a new means for quantitative myelin mapping. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Quantitative nmr microscopy of multicellular tumor spheroids and confrontation cultures

In cancer research, tumor spheroids are a well established system to study tumor metabolism resembling the situation in vivo more closely cell monolayers. Spherical aggregates of malignant melanoma cells (MV3) and their invasion into rat brain aggregates have been investigated by quantitative NMR microscopy. Relaxation times (T₁, T₂) and diffusion parameter images were acquired with an in-plane resolution of 14 × 14 μm². The authors were able to demonstrate that the morphology of the spheroids can be visualized on these NMR maps. The contrast was mainly manifested in relaxation maps, where average relaxation times T₁ = 1.94 ± 0.17 s and T₂ = 42.8 ± 6.3 ms were obtained for proliferating cells, and T₁ = 2.49 ± 0.31 s and T₂ = 104.3 ± 29.4 ms for the necrobiotic center. The mean diffusion coefficients were 0.59 ± 0.12 μm²/ms and 0.85 ± 0.14 μm²/ms, respectively. The authors could follow the dynamic process of tumor cell invasion in the investigated co-culture system. Knowledge about tumor cell migration and tumor cell invasion is essential for the understanding of cancer and its therapy. Quantitative NMR microscopy can study this dynamic process noninvasively and therefore may help to assess the influence of therapy on the micromilieu of these spheroids.     

The effect of perfusion on T1 after slice-selective spin inversion in the isolated cardioplegic rat heart: Measurement of a lower bound of intracapillary-extravascular water proton exchange rate

Many NMR measurements of cardiac microcirculation (perfusion, intramyocardial blood volume) depend on some kind of assumption of intracapillary-extravascular water exchange rate, e.g., fast exchange. The magnitude of this water exchange rate, however, is still unknown. The intention of this study was to determine a lower limit for this exchange rate by investigating the effect of perfusion on relaxation time. Studies were performed in the isolated perfused cardioplegic rat heart. After slice-selective inversion, the spin lattice relaxation rate of myocardium within the slice was studied as a function of perfusion and compared with a mathematical model which predicts relaxation rate as a function of perfusion and intracapillary-extravascular exchange rate. A linear relationship was found between relaxation rate T^?1 and perfusion P normalized by perfusate/tissue partition coefficient of water, λ: ΔT^?1 = m · ΔP/λ with 0.82 ≤ m ≤ 1.06. Insertion of experimental data in the model revealed that a lower bound of the exchange rate from intra-to extravascular space is 6.6 s^?1 (4.5 s^?1, P < 0.05), i.e., the intracapillary lifetime of a water molecule is less than 150 ms (222 ms, P < 0.05). Based on this finding, the T₁ mapping after slice-selective inversion could become a valuable noncontrast NMR method to measure variations of perfusion.     

Longitudinal and multi-echo transverse relaxation times of normal breast tissue at 3 Tesla

Purpose

To measure longitudinal (T₁) and multi‐echo transverse (T₂) relaxation times of healthy breast tissue at 3 Tesla (T).

Materials and Methods

High‐resolution relaxation time measurements were made in six healthy female subjects. Inversion recovery images were acquired at 10 inversion times between 100 ms and 4000 ms, and multiple spin echo images were acquired at 16 echo times between 10 ms and 160 ms.

Results

Longitudinal relaxation times T₁ were measured as 423 ± 12 ms for adipose tissue and 1680 ± 180 ms for fibroglandular tissue. Multi‐echo transverse relaxation times T₂ were measured as 154 ± 9 ms for adipose tissue and 71 ± 6 ms for fibroglandular tissue. Histograms of the voxel‐wise relaxation times and quantitative relaxation time maps are also presented.

Conclusion

T₁ and multi‐echo T₂ relaxation times in normal human breast tissue are reported. These values are useful for pulse sequence design and optimization for 3T breast MRI. Compared with the literature, T₁ values are significantly longer at 3T, suggesting that longer repetition time and inversion time values should be used for similar image contrast. J. Magn. Reson. Imaging 2010;32:982–987. © 2010 Wiley‐Liss, Inc.     

Synchronized inversion recovery-spin echo sequences for precise in vivo T1 measurement of human myocardium: A pilot study on 22 healthy subjects

An ECG-triggered, two-sequence MRI technique is proposed for the precise measurement of proton T₁ relaxation times of the human myocardium at a field strength of 0.5 T. The combination of an inversion recovery (IR) sequence and a spin echo (SE) sequence is not new. It is, however, rarely used in quantitative in vivo cardiac studies. Our approach employs a synchronization of the 90° read pulse to the systolic period. In a study of 22 healthy volunteers, the globally measured T₁ value was estimated to be 714 ± 23 ms. Four of the volunteers also underwent additional imaging scans for the purposes of reproducibility assessment. The T₁ precision was found to be 3.9 ± 1.1% for the IR/SE combination and 16.9 ± 5.3% for a combination of SE sequences. Total imaging time for the IR and SE sequences was 19.2 ± 3.0 mins. The relative rapidity of this classic technique and the T₁ precision obtained give this technique an obvious application in the discrimination of normal and diseased myocardium. In the same study, valuable supplementary tissue characterization is provided by T₂, calculated from the SE sequence. T₂ was evaluated to be 50 ± 3 ms.     

Blood oxygen saturation assessment in vivo using T2 * estimation

The feasibility of noninvasively assessing hemoglobin oxygen saturation of deep blood vessels in vivo by measuring blood T₂* is investigated. Techniques for blood T₂* measurements in major arteries and veins in the presence of pulsatile blood flow are presented and validated using a flow phantom. Images of multiple TEs were collected in a paired fashion. Cardiac triggering was used to eliminate image artifacts caused by pulsatile arterial blood flow. Using these techniques, it was found that the T₂* of arterial blood (199 ± 8 ms) is significantly greater than that of venous blood (108 ± 6 ms) in 10 volunteers, consistent with the fact that the oxygen saturation level of arterial blood is much larger than that of venous blood. Various oxygen saturation levels were created in vivo in a pig and the blood T₂* was shown to increase with oxygen saturation levels over a wide range. Preliminary results of this study indicate that it is feasible to assess local oxygen saturation by measuring blood T₂* using the proposed techniques.     

Modified Look‐Locker T1 evaluation using Bloch simulations: Human and phantom validation

Modified Look‐Locker imaging is frequently used for T₁ mapping of the myocardium. However, the specific effect of various MRI parameters (e.g., encoding scheme, modifications of flip angle, heart rate, T₂, and inversion times) on the accuracy of T₁ measurement has not been studied through Bloch simulations. In this work, modified Look‐Locker imaging was characterized through a numerical solution for Bloch equations. MRI sequence parameters that may affect T₁ accuracy were systematically varied in the simulation. For validation, phantoms were constructed with various T₂ and T₁ times and compared with Bloch equation simulations. Human volunteers were also evaluated with various pulse sequences parameters to assess the validity of the numerical simulations. There was close agreement between simulated T₁ times and T₁ times measured in phantoms and volunteers. Lower T₂ times (i.e., <30 ms) resulted in errors greater than 5% for T₁ determination. Increasing maximum inversion time value improved T₁ accuracy particularly for precontrast myocardial T₁. Balanced steady‐state free precession k space centric encoding improved accuracy for short T₁ times (post gadolinium), but linear encoding provided improved accuracy for precontrast T₁ values. Lower flip angles are preferred if the signal‐to‐noise ratio is sufficiently high. Bloch simulations for modified Look‐Locker imaging provide an accurate method to comprehensively quantify the effect of pulse sequence parameters on T₁ accuracy. As an alternative to otherwise lengthy phantom studies or human studies, such simulations may be useful to optimize the modified Look‐Locker imaging sequence and compare differences in T₁‐derived measurements from different scanners or institutions. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

MR Spectroscopic imaging of collagen: Tendons and knee menisci

Water molecules associated with collagen have short transverse (T₂) relaxation times. Projection-reconstruction techniques are able to achieve an echo time (TE) much shorter than conventional techniques, allowing imaging of tissues with T₂ < 5 ms. Using these techniques, a conventional 1.5-T MRI human imaging system can directly image collagen-associated water from knee menisci and tendons in normal volunteers and patients. Long-T₂ suppression improves the contrast between these structures and the surrounding tissue with long-T₂ relaxation times. Spectroscopic imaging provides improved lipid/water registration and information about chemical composition and relaxation times. Direct imaging of tendons and menisci may provide more information about these structures and provide a new way to assess both injury and repair.     

Accurate determination of spin-density and T1 in the presence of RF-field inhomogeneities and flip-angle miscalibration

A method is presented for the accurate extraction of relative spin-density (ρo) and spin-lattice relaxation time (T₁) in the presence of RF-field inhomogeneities and flip-angle miscalibration. The method requires collecting images at several flip-angles with a three-dimensional, spoiled steady-state, gradient-echo imaging sequence. Results show that the predominant effect of an overestimated flip-angle is to shift the T₁ estimate to a higher value, whereas reductions in the normalized RF-field from unity cause ρo and T₁ distributions to be skewed toward lower values. Phantom and in vivo results demonstrate that the proposed method overcomes both of these systematic errors. The method was shown to be valid for up to a 50% reduction in RF sensitivity. A self-consistency argument was used to validate the absence of systematic errors in the extracted ρo and T₁ values over a large number of voxels. This made it possible to obtain a very precise estimate of muscle T₁ at 1.5 T, yielding a 95% confidence interval of (1077.7 ± 3.5) ms.     

Evaluation of cerebral gray and white matter metabolite differences by spectroscopic imaging at 4.1T

Using a 4.1 T whole body system, we have acquired ¹H spectroscopic imaging (SI) data of N-acetyl (NA) compounds, creatine (CR), and choline (CH) with nominal voxel sizes of 0.5 cc (1.15 cc after filtering). We have used the SI data to estimate differences in cerebral metabolites of human gray and white matter. To evaluate the origin of an increased CWNA and CWNA ratios in gray matter relative to white matter, we measured the T₁ and T₂ of CR, NA, and CH in gray and white matter using moderate resolution SI imaging. In white matter the T₂s of NA, CR, and CH were 233 ± 27,141 ± 18, and 167 ± 20 ms, respectively, and 227 ± 27,140 ± 16, and 189 ± 25 ms in gray matter. The T, values for NA, CR, and CH were 1267 ±141, 1487 ± 146, and 1111 ± 136 ms in gray matter and 1260 ± 154, 1429 & 233, and 1074 ± 146 ms in white matter. After correcting for T₁ and T₂ losses, creatine content was significantly lower in white matter than gray (P < e 0.01, t-test), with a white/gray content ratio of 0.8, in agreement with biopsy and in vivo measurements at 1.5 and 2.0T.     

High-resolution in vivo measurements of transverse relaxation times in rats at 7 Tesla

A multi-echo imaging sequence suitable for high-resolution and accurate in vivo transverse relaxation time (T₂) mapping has been implemented. The sequence was tested on phantoms and was used to measure T₂ values in vivo in the rat brain, muscle, and fat at 7 T. Brain T₂ maps are shown and regional variations in brain T₂ are reported (41.8 ms in cortex, 47.9 ms in hippocampus). Results are compared to literature values obtained at lower field in vivo as well as high-field T₂ measurements on excised rat tissues. The reported T₂ values are generally smaller compared to lower-field-strength literature values. A discussion of the possible causes of these field effects on T₂ is included (dipolar interaction, fast chemical exchange, and diffusion in susceptibility gradients).     

Accurate measurement of T1 in vivo in less than 3 seconds using echo-planar imaging

This paper describes a rapid and accurate method for meassuring T₁ in vivo using an echo-planar imaging version of the Look-Locher sequence. T₁ values from 76 to 1330 ms have been measured in 3 s with a mean accuracy of 4.6%.     

A technique for rapid single‐echo spin‐echo T2 mapping

A rapid technique for mapping of T₂ relaxation times is presented. The method is based on the conventional single‐echo spin echo approach but uses a much shorter pulse repetition time to accelerate data acquisition. The premise of the new method is the use of a constant difference between the echo time and pulse repetition time, which removes the conventional and restrictive requirement of pulse repetition time ? T₁. Theoretical and simulation investigations were performed to evaluate the criteria for accurate T₂ measurements. Measured T₂s were shown to be within 1% error as long as the key criterion of pulse repetition time/T₂ ≥3 is met. Strictly, a second condition of echo time/T₁ ? 1 is also required. However, violations of this condition were found to have minimal impact in most clinical scenarios. Validation was conducted in phantoms and in vivo T₂ mapping of healthy cartilage and brain. The proposed method offers all the advantages of single‐echo spin echo imaging (e.g., immunity to stimulated echo effects, robustness to static field inhomogeneity, flexibility in the number and choice of echo times) in a considerably reduced amount of time and is readily implemented on any clinical scanner. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

In vivo measurement of T*2 and field inhomogeneity maps in the human heart at 1.5 T

Cardiac echo-planar imaging suffers invariably from regions of severe distortion and T*₂ decay in the myocardium. The purpose of this work was to perform local measurements of T*₂ and field inhomogeneities in the myocardium and to identify the sources of focal signal loss and distortion. Field inhomogeneity maps and T*₂ were measured in five normal volunteers in short-axis slices spanning from base to apex. It was found that T*₂ ranged from 26 ms (SD = 7 ms, n = 5) to 41 ms (SD = 11 ms, n = 5) over most of the heart, and peak-to-peak field inhomogeneity differences were 71 Hz (SD = 14 Hz, n = 5). In all hearts, regions of severe signal loss were consistently adjacent to the posterior vein of the left ventricle; T*₂ in these regions was 12 ms (SD = 2 ms, n = 5), and the difference in resonance frequency with the surrounding myocardium was 70-100 Hz. These effects may be caused by increased magnetic susceptibility from deoxygenated blood in these veins.