Homonuclear uncoupled 1H-spectroscopy of the human brain using weighted accumulation schemes.

Homonuclear uncoupled H-spectroscopy based on 2-dimensional (2D) J-resolved spectroscopy is a well suited technique for the assessment of J-coupled metabolite resonances. In comparison with 1-dimensional H-spectroscopy this technique largely reduces problems due to spectral overlap between low molecular weight metabolite resonances and superimposed broad macromolecule resonances, as well as overlap between adjacent multiplets. Usually, 2D J-resolved spectroscopic data were acquired using a constant number of accumulations for each of the various echo times. In contrast to this, a weighted accumulation scheme has been applied in this study, using an echo time dependent number of accumulations. The aims of this modification were to reduce the acquisition time and to improve the signal-to-noise ratio per unit acquisition time (SNRt). Four different sine-bell like accumulation schemes and a reference scheme using a constant number of accumulations have been applied on five normal volunteers. Localized spectra obtained from the parieto-occipital white matter were compared with regard to SNRt and linewidth. A reduction in acquisition time of 45%, related to the reference scheme, and an increase in SNRt of 25-30% were achieved using a sine-bell accumulation scheme in combination with a quarter sine-wave apodization of the short echo time data. Down to an acquisition time of 122 s no significant line broadening has been observed in comparison with the reference scheme.     

In vivo localized1H-spectroscopy with spin echos and stimulated echos: A quantitative comparison

Stimulated echos (STE) are frequently used for localization inin vivo spectroscopy. However, in theory the signal is reduced by a factor of 2 compared to spin echos. We have compared the STEAM technique and a method utilizing a double spin echo (DSE) for localization. Projections and spectra of phantoms and the human brain have been measured with a 4 T whole body system. Both methods provide a reliable localization in one scan. The spectra obtained with both techniques are similar, with one significant exception: the DSE signal strength is stronger than that of STEAM by a factor of about 1.9. The advantages and disadvantages of both methods with respect to RF- power, gradient strength, and spectral editing will be discussed.     

Cerebral tissue water spin-spin relaxation times in human neonates at 2.4 tesla: methodology and the effects of maturation

Using a 4-echo spin-echo sequence, cerebral T2 was measured in specific anatomic regions in eleven healthy newborn infants, whose gestational plus postnatal ages (GPAs) lay between 37 and 42 weeks. For a region in the pons, T2 was 141+/-9 ms (mean +/- standard deviation), and no significant dependence upon GPA was seen. In the thalamus mean T2 was 136+/-13 ms, and T2 demonstrated a significant negative linear dependence upon age (r = 0.690; p < 0.02). In periventricular and frontal regions, mean T2 were 217+/-33, and 228+/-32 ms respectively, and more marked negative linear correlations with age were observed (r = 0.833; p < 0.001 and r = 0.722; p < 0.02). For these regions, the rate of T2 decrease with age appeared to be related to known patterns of myelination. For the parietal region studied, mean T2 was 204+/-34 ms, no significant dependence upon GPA being seen. T2 shows promise as an objective measure of cerebral development in the perinatal period.     

In vivo 1H NMR spectroscopy of individual human brain metabolites at moderate field strengths

This article reviews spectral editing techniques for in vivo ¹H NMR spectroscopy of human brain tissue at moderate field strengths of 1.5–3 Tesla. Various aspects of ¹H NMR spectroscopy are discussed with regard to in vivo applications. The parameter set [δ, J, n] (δ being the relative chemical shift, J the scalar coupling constant and n the number of coupled spins) is used to characterize the spin systems under investigation and to classify the editing techniques that are used in in vivo ¹H NMR spectroscopy.     

Establishing norms for age-related changes in proton T1 of human brain tissue in vivo

The goal of this study was to determine the expected normal range of variation in spin-lattice relaxation time (T₁) of brain tissue in vivo, as a function of age. A previously validated precise and accurate inversion recovery method was used to map T₁ transversely, at the level of the basal ganglia, in a study population of 115 healthy subjects (ages 4 to 72; 57 male and 58 female). Least-squares regression analysis shows that T₁ varied as a function of age in pulvinar nucleus (R² = 56%), anterior thalamus (R² = 51%), caudate (R² = 50%), frontal white matter (R² = 47%), optic radiation (R² = 39%), putamen (R² = 36%), genu (R² = 22%), occipital white matter (R² = 20%) (all p < 0.0001), and cortical gray matter (R² = 53%) (p < 0.001). There were no significant differences in T₁ between men and women. T₁ declines throughout adolescence and early adulthood, to achieve a minimum value in the fourth to sixth decade of life, then T₁ begins to increase. Quantitative magnetic resonance imaging provides evidence that brain tissue continues to change throughout the lifespan among healthy subjects with no neurologic deficits. Age-related changes follow a strikingly different schedule in different brain tissues; white matter tracts tend to reach a minimum T₁ value, and to increase again, sooner than do gray matter tracts. Such normative data may prove useful for the early detection of brain pathology in patients.     

Quantitative SENSE-MRSI of the human brain

Purpose

To develop a method for estimating metabolite concentrations using phased-array coils and sensitivity-encoded (SENSE) magnetic resonance spectroscopic images (MRSI) of the human brain.

Materials and Methods

The method is based on the phantom replacement technique and uses receive coil sensitivity maps and body-coil loading factors to account for receive B₁ inhomogeneity and variable coil loading, respectively. Corrections for cerebrospinal fluid content from the MRSI voxel were also applied, and the total protocol scan time was less than 15 min. The method was applied to 10 normal human volunteers using a multislice 2D-MRSI sequence at 3 T, and seven different brain regions were quantified.

Results

N-Acetyl aspartate (NAA) concentrations varied from 9.7 to 14.7 mM, creatine (Cr) varied from 6.6 to 10.6 mM and choline (Cho) varied from 1.6 to 3.0 mM, in good general agreement with prior literature values.

Conclusions

Quantitative SENSE-MRSI of the human brain is routinely possible using an adapted phantom-replacement technique. The method may also be applied to other MRSI techniques, including conventional phase encoding, with phased-array receiver coils, provided that coil sensitivity profiles can be measured.     

In vivo NMR imaging and T1 measurements of water protons in the human brain

Nuclear magnetic resonance (NMR) proton density images of the human brain have been made by the FONAR method. Spin-lattice relaxation times, T₁, of water hydrogen protons have been determined at random positions within frontal and temporal regions of the human brain. The primary purpose of this ongoing research is to accumulate a large data base of normal T₁ values for water protons in normal human brain tissue. Our experience to data includes 31 measurements on 18 volunteer subjects, and the mean value ± standard deviation is 215 ± 42 msec. In addition, two metastatic lesions of the brain were studied and found to have T₁ values longer than those for normal brain tissue.     

Optimised in vivo visualisation of cortical structures in the human brain at 3 T using IR-TSE

The primary visual cortex in humans can be identified using magnetic resonance imaging (MRI) in vivo by detection of the stria of Gennari. To fully characterize this area, high spatial resolution is essential, including the use of very thin image slices to avoid loss of definition due to partial volume effects. A three-dimensional magnetization-prepared turbo spin-echo sequence, with appropriate parameter optimization, provided high-resolution imaging (0.4 x 0.4 x 0.5 mm3) on a clinical 3-T scanner with adequate contrast to noise ratio. These images allowed visualisation of the stria of Gennari in every slice of a volume covering most of the occipital cortex, in each of six healthy volunteers. The effective longitudinal relaxation time was measured with the isotropic resolution turbo spin echo sequence and found to be substantially shorter than values measured with a dedicated relaxometric sequence. The shortening was attributed to magnetization transfer effects, as supported by the investigation of its slab and turbo-factor dependence.     

Dynamic Nuclear Polarization of [1-C]pyruvic acid at 4.6 tesla

Dynamic Nuclear Polarization (DNP) of the ¹³C nucleus has been investigated for [1-¹³C]pyruvic acid, doped with the trityl radical OX063Me, at 4.64 T and 1.15 K. The dependence of the polarization on microwave frequency, radical concentration and electron saturation was studied. For optimized conditions, a ¹³C polarization equal to 64 ± 5% was obtained, an increase by more than a factor of two compared with earlier results at 3.35 T of the same system. It was furthermore observed that the addition of gadolinium, which resulted in a twofold polarization increase at 3.35 T, only resulted in a minor improvement at 4.64 T. The dependence of the electron saturation on microwave frequency and microwave power was quantified by first moment measurements which were obtained by nucleus–electron double resonance (NEDOR) experiments. Complete electron saturation was observed for a microwave frequency close to the centre frequency of the ESR line, and by using maximum power of the microwave source. The DNP build-up time at 4.64 T (3000 s) was prolonged by approximately a factor three over the build-up time at 3.35 T (1200 s). However, after approximately 20 min of microwave irradiation the polarization at 4.64 T exceeded the polarization at 3.35 T.     

Simple RF design for human functional and morphological cardiac imaging at 7 tesla

Morphological and functional cardiac MRI can potentially benefit greatly from the recent advent of commercial high-field (7 tesla and above) MRI systems. However, conventional hardware configurations at lower field using a body-coil for homogeneous transmission are not available at these field strengths. Sophisticated multiple-transmit-channel systems have been shown to be able to image the human heart at 7 tesla but such systems are currently not widely available. In this paper, we empirically optimize the design of a simple quadrature coil for cardiac imaging at 7 tesla. The size, geometry, and position have been chosen to produce a B₁ field with no tissue-induced signal voids within the heart. Standard navigator echoes for gating were adapted for operation at the heart/lung interface, directly along the head–foot direction. Using this setup, conventional and high-resolution cine functional imaging have been successfully performed, as has morphological imaging of the right coronary artery.     

Liver imaging at 1.5 tesla: pulse sequence optimization based on improved measurement of tissue relaxation times

In order to predict the most sensitive MR imaging sequence for detecting liver metastases at 1.5 T, in vivo measurements of T1 and T2 relaxation times and proton density were obtained using multipoint techniques. Based on these measurements, two-dimensional contrast contour plots were constructed demonstrating signal intensity contrast between hepatic lesions and surrounding liver parenchyma for different pulse sequences and pulse timing parameters. The data predict that inversion recovery spin echo (IRSE) imaging should yield the greatest contrast between liver metastases and liver parenchyma at 1.5 T, followed by short tau inversion recovery (STIR) and spin-echo (SE) pulse sequences. T2-weighted SE images provided greater liver/lesion contrast than T1-weighted SE pulse sequences. Calculated T1, T2, and proton density values of the spleen were similar to those of hepatic metastatic lesions, indicating that the signal intensity of the spleen may be used as an internal standard to predict the signal intensity of hepatic metastases on T1- and T2-weighted images at 1.5 T.     

A method for in vivo assessment of reversible rat pancreatic ischemia using 31P NMR spectroscopy at 2.0 tesla

A surgical method is described which allows in vivo assessment of reversible rat pancreatic ischemia using ³¹P NMR spectroscopy at 2.0 T. Phosphorous-31 NMR spectra acquired during the ischemic period show the expected increase in inorganic phosphate with a concomitant decrease in ATP levels and pH as compared to controls. Upon reperfusion, inorganic phosphate and ATP returned to control levels while pH recovered to a more alkaline value. This method provides a means of studying in vivo changes in high energy metabolite associated with acute pancreatitis (AP) and maintains the secretory ability of the gland so that different forms of AP, such as those arising from pancreatic juice edema, can be studied.     

Novel peak assignments of in vivo (13)C MRS in human brain at 1.5 T

(13)C MRS studies at natural abundance and after intravenous 1-(13)C glucose infusion were performed on a 1.5-T clinical scanner in four subjects. Localization to the occipital cortex was achieved by a surface coil. In natural abundance spectra glucose C(3beta,5beta), myo-inositol, glutamate C(1,2,5), glutamine C(1,2,5), N-acetyl-aspartate C(1-4,C=O), creatine CH(2), CH(3), and C(C=N), taurine C(2,3), bicarbonate HCO(-)(3) were identified. After glucose infusion (13)C enrichment of glucose C(1alpha,1beta), glutamate C(1-4), glutamine C(1-4), aspartate C(2,3), N-acetyl-aspartate C(2,3), lactate C(3), alanine C(3), and HCO(-)(3) were observed. The observation of (13)C enrichment of resonances resonating at >150 ppm is an extension of previously published studies and will provide a more precise determination of metabolic rates and substrate decarboxylation in human brain.     

In vivo imaging of the human brain at 1.5 T with 0.6-mm isotropic resolution

We present high-resolution in vivo anatomical scans with 3D whole-brain coverage and an isotropic resolution of 0.6 mm, obtained at a clinical field of 1.5 T. The data are acquired in 10 independent scans over two sessions using a 3D magnetization-prepared, gradient echo sequence, modified to output phase images in addition to magnitude images. The independent scans are coregistered to correct for head motion, prior to performing complex averaging. The resolution of the final, averaged image, is found to be equal to the nominal one.     

In vivo 1H spectroscopic studies of human gastrocnemius muscle at 1.5 T

In vivo high resolution 1H magnetic resonance spectra are observed from the gastrocnemius muscle in 12 normal volunteers. The gross spectral features do not appear to significantly change from individual to individual. However, the number and the relative amplitudes of the resonances from the fatty acid chains are found to exhibit significant variation from normal to normal. The spectra observed on different occasions in the same individual exhibit very little variation. Our studies indicate that it is preferable to use the spin echo sequence with a long echo time to observe water-suppressed proton spectra from the muscle tissue.     

Action of nitric oxide on healthy and inflamed human dental pulp tissue

Irreversible pulpitis has been associated with pain and an increase in the number of pulp inflammatory cells. Based on the action of nitric oxide (NO) elsewhere, NO may possibly participate in the sensory and autonomic innervation of the dental pulp, and may influence local inflammatory responses. The purpose of this study was to analyze normal and inflamed human dental pulp for the presence of NADPH-diaphorase (NADPH-d), as an index of NO system activity. Six non-carious second premolar pulp tissue samples were obtained from young patients who required extractions for orthodontic reasons and six inflamed samples were obtained from symptomatic carious second premolars clinically diagnosed with irreversible pulpitis. Pulp tissue was carefully removed, fixed by immersion in a cold 4% PFA buffered solution for 120min, rinsed in cold phosphate buffer, and quickly-frozen for cryostat sectioning. Pulp tissue was sectioned perpendicularly to the vertical axis of the tooth at 20mum and processed for histochemistry. Sections of each specimen were stained with hematoxylin-eosin and other sections were subjected to histochemical NADPH-d detection. Results indicated the presence of NADPH reactivity within the pulps of both normal and carious teeth. In the normal teeth NADPH-d activity was detected in a small number of vascular endothelial cells and fibroblasts. The inflammatory response of the pulp from carious premolars was detected in connective tissue by the presence of an increased number of fibroblasts, angioblasts and collagen fibers. It was possible to determine the extent of odontoblast reactivity since the odontoblast layer was usually absent in these split-peel preparations. There were no obvious signs of stained pulpal nerve fibers. Overall NADPH-d staining was significantly more intense within inflamed pulp tissues compared to normal healthy samples (Mann-Whitney test, p<0.002). These results suggest that NADPH-d may be used as a marker of inflammatory activity in pulpitis and provide the basis for further studies aiming to clarify the possible functions of NO in human dental pulp in pathophysiological situations.     

Measurement of in vivo multi-component T2 relaxation times for brain tissue using multi-slice T2 prep at 1.5 and 3 T

The objective of this study was to implement a clinically relevant multi-slice multi-echo imaging sequence in order to quantify multi-component T2 relaxation times for normal volunteers at both 1.5 and 3 T. Multi-echo data were fitted using a nonnegative least square algorithm. Twelve echo data with nonlinear echo sampling were acquired using a receive-only eight-channel phased array coil and volume head coil for phantoms and normal volunteers, and compared to 32-echo data with linear echo sampling. It was observed that the performance of the 180 degrees refocusing trains was more spatially uniform for the receive-only eight-channel phased array coil than for the head coil, particularly at 3 T. The phantom study showed that the estimated T2 relaxation times were accurate and reproducible for both single- and multi-slice acquisition from a commercial phantom with known T2 relaxation times. Short T2 components (T2 <50 ms) were mainly observed within the white matter for normal volunteers, and the fraction of short T2 water components (i.e., myelin water) was 7-12% of total water. It was observed that the calculated myelin water fraction map from the nonlinearly sampled 12-echo data was comparable with that from the linearly sampled 32-echo data. Quantification of T2 relaxation times from multi-slice images was accomplished with a clinically acceptable scan times (16 min) for normal volunteers by using a nonselective T2 prep imaging sequence. The use of the eight-channel head coil involved more accurate quantification of T2 relaxation times particularly when the number of echoes was limited.     

Short‐term effects of synchrotron irradiation on vasculature and tissue in healthy mouse brain

The purpose of this study is to measure the effects of a tomographic synchrotron irradiation on healthy mouse brain. The cerebral cortexes of healthy nude mice were irradiated with a monochromatic synchrotron beam of 79 keV at a dose of 15 Gy in accordance with a protocol of photoactivation of cisplatin previously tested in our laboratory. Forty‐eight hours, one week and one month after irradiation, the blood brain barrier (BBB) permeability was measured in the irradiated area with intravital multiphoton microscopy using fluorescent dyes with molecular weights of 4 and 70 kDa. Vascular parameters and gliosis were also assessed using quantitative immunohistochemistry. No extravasation of the fluorescent dyes was observed in the irradiated area at any measurement time (48 h, 1 week, 1 month). It appears that the BBB remains impermeable to molecules with a molecular weight of 4 kDa and above. The vascular density and vascular surface were unaffected by irradiation and no gliosis was induced. These findings suggest that a 15 Gy/79 keV synchrotron irradiation does not induce important damage on brain vasculature and tissue on the short term following irradiation.     

Automated data processing of [1H-decoupled] 13C MR spectra acquired from human brain in vivo

In clinical 13C infusion studies, broadband excitation of 200 ppm of the human brain yields 13C MR spectra with a time resolution of 2-5 min and generates up to 2000 metabolite peaks over 2h. We describe a fast, automated, observer-independent technique for processing [1H-decoupled] 13C spectra. Quantified 13C spectroscopic signals, before and after the administration of [1-13C]glucose and/or [1-13C]acetate in human subjects are determined. Stepwise improvements of data processing are illustrated by examples of normal and pathological results. Variation in analysis of individual 13C resonances ranged between 2 and 14%. Using this method it is possible to reliably identify subtle metabolic effects of brain disease including Alzheimer's disease and epilepsy.