ECG-gated <Superscript>23</Superscript>Na-MRI of the human heart using a 3D-radial projection technique with ultra-short echo times

Pathological changes in tissue often manifest themselves in an altered sodium gradient between intra- and extracellular space due to a malfunctioning Na⁺–K⁺ pump, resulting in an increase in total sodium concentration in ischaemic regions. Therefore, ²³Na-MRI has the potential to non-invasively differentiate viable from non-viable tissue by detecting concentration changes of intra- and extracellular sodium. As the in vivo sodium signal shows a bi-exponential T₂ decay, with a short component of less than 1 ms, the accurate quantification of the total sodium content requires imaging techniques with ultra-short echo times (TE) below 0.5 ms. A 3D-radial projection technique has been developed which allows the acquisition of ECG-triggered sodium images of the human heart with a TE of 0.4 ms. With this pulse sequence ²³Na-MRI volunteer measurements of the head or the heart were performed in less than 18 min on a 1.5-T clinical scanner with an isotropic resolution of 10 mm³. The signal to noise ratio of the radial projection technique is twofold higher than that of a Cartesian gradient echo pulse sequence (TE = 3.2 ms). Radial ²³Na-MRI provides a tool for clinical studies, aiming at the differentiation of viable and non-viable tissue.     

Time-domain quantitation of <Superscript>1</Superscript>H short echo-time signals: background accommodation

Quantitation of ¹H short echo-time signals is often hampered by a background signal originating mainly from macromolecules and lipids. While the model function of the metabolite signal is known, that of the macromolecules is only partially known. We present time-domain semi-parametric estimation approaches based on the QUEST quantitation algorithm (QUantitation based on QUantum ESTimation) and encompassing Cramér–Rao bounds that handle the influence of nuisance parameters related to the background. Three novel methods for background accommodation are presented. They are based on the fast decay of the background signal in the time domain. After automatic estimation, the background signal can be automatically (1) subtracted from the raw data, (2) included in the basis set as multiple components, or (3) included in the basis set as a single entity. The performances of these methods combined with QUEST are evaluated through extensive Monte Carlo studies. They are compared in terms of bias–variance trade-off. Because error bars on the amplitudes are of paramount importance for diagnostic reliability, Cramér–Rao bounds accounting for the uncertainty caused by the background are proposed. Quantitation with QUEST of in vivo short echo-time ¹H human brain with estimation of the background is demonstrated.     

In vivo quantification of response to treatment in patients with multiple myeloma by <Superscript>1</Superscript>H magnetic resonance spectroscopy of bone marrow

Object Magnetic resonance imaging (MRI) is the gold standard non-invasive technique to detect malignant disease in the bone marrow. Proton magnetic resonance spectroscopy (MRS) can be performed as a quick adjunct to routine spinal MRI. We performed proton MRS to patients with multiple myeloma (MM) at diagnosis and after treatment to investigate the possible correlation of MRS data with response to therapy. Patients and methods Twenty-one patients with newly diagnosed MM underwent combined MRI/MRS explorations of a transverse center section in the fifth lumbar vertebral body. MRS was acquired with STEAM and 40 ms TE. Areas of unsuppressed water and lipid resonances were used to calculate the lipid-to-water ratio (LWR). Results No association was detected between initial LWRs and the clinical characteristics of patients. Post treatment MRS was available in 16 patients of whom 11 (69%) presented an LWR increase, this included all complete responders (8/8, 100%, P = 0.012). A post-treatment LWR value equal to or larger than one is proposed as a non-invasive marker of complete response to treatment. Conclusion Only patients responding to treatment presented a significant increase in bone marrow LWR after therapy. MRS may provide an adequate quantification of response to chemotherapy in patients with MM.     

MRI of the lung using hyperpolarized <Superscript>3</Superscript>He at very low magnetic field (3 mT)

Optical pumping of ³He produces large (hyper) nuclear-spin polarizations independent of the magnetic resonance imaging (MRI) field strength. This allows lung MRI to be performed at reduced fields with many associated benefits, such as lower tissue susceptibility gradients and decreased power absorption rates. Here we present results of 2D imaging as well as accurate 1D gas diffusion mapping of the human lung using ³He at very low field (3 mT). Furthermore, measurements of transverse relaxation in zero applied gradient are shown to accurately track pulmonary O₂ partial pressure, opening the way for novel imaging sequences.     

<Superscript>1</Superscript>H MR spectroscopy as a diagnostic tool for cerebral creatine deficiency

Objective  Total creatine (tCr) constitutes one of the most prominent signals in human brain MR spectra. A significant decrease in the tCr signal indicates a severe disorder of creatine metabolism. We describe the potential of ¹H MR spectroscopy in differential diagnosis of creatine transporter (SLC6A8) deficiency syndrome. Materials and methods  Two siblings, a 7-year-old female presenting with mild psychomotor delay, and a 5-year-old male with severe psychomotor retardation, epilepsy and autistic spectrum of problems including speech delay, underwent MR examination because of suspected creatine deficiency. After the MRI examination, ¹H MR spectroscopy using the CSI technique was performed. Results  Metabolic images of N-acetylaspartate, tCr and choline concentrations showed a very low tCr signal in the male, which was approximately three times lower than in his sister (male/female/controls: tCr = 1.6/4.6/7.5 mM). Despite creatine supplementation, no improvement in clinical status and tCr concentration in the MR spectra of the male was observed and diagnosis of SLC6A8 deficiency was proposed. Sequence analysis of the SLC6A8 gene revealed a novel pathogenic frameshift mutation c.219delC; p.Asn74ThrfsX23, hemizygous in the male and heterozygous in the female. Conclusions  The diagnosis of X-linked mental retardation caused by the SLC6A8 deficiency can be independently established by ¹H MR spectroscopy.     

Transmit/receive headcoil for optimal <Superscript>1</Superscript>H MR spectroscopy of the brain in paediatric patients at 3 T

¹H magnetic resonance (MR) spectroscopy is a useful tool to obtain metabolic information from the brain in paediatric patients. To detect signals of metabolites at low concentrations or from small volumes, the signal-to-noise ratio (SNR) has to be optimized. The SNR can be increased by going to higher field strengths. However, this leads to higher spectral bandwidths, which increases the chemical shift artefact. Here we present a transmit/receive headcoil which is adapted to the dimensions of the paediatric head and enables PRESS localization with high radio-frequency (RF) bandwidths that minimize the chemical shift displacement to only 5%. In addition, since the pulse lengths are shorter with higher RF bandwidths, the echo time can be reduced to 10 ms improving SNR as well.Parts of this work have been presented at the European Society for Magnetic Resonance in Medicine and Biology in Rotterdam in 2003     

Detection of myocardial viability in acute infarction using contrast-enhanced <Superscript>1</Superscript>H magnetic resonance imaging

Background Reperfusion strategies salvage myocardium at risk in acute myocardial infarction (MI). This clinical study was performed to determine whether areas without evidence of delayed MRI contrast enhancement in MI correspond to viability by means of percent systolic wall thickening (%SWT) and enddiastolic wall thickness (EDWT) in chronic infarction. Methods Twenty MRI studies were performed in ten patients within 6 days of MI and 3 months post-MI. On a segmental basis the percentage of viable myocardium as defined by contrast-enhanced MRI (no delayed MRI contrast enhancement) in acute MI was measured and was compared with %SWT and EDWT in chronic MI. Results Of the 1718 segments in acute infarction in which the percentage of viable myocardium was measured 1333 were found to be completely viable by means of contrast-enhanced MRI (no delayed MRI contrast enhancement). All of these segments revealed %SWT on day 90 post-MI, and 97% of segments were viable by means of an EDWT of more than 5.5 mm. In 85 segments the proportion of viable myocardium was 50–99% (mean 56±8%), with 92% segments found to be viable by means of %SWT and 92% by EDWT, and of 156 segments with viable myocardium between 1–49% (36±8%) 79% were found to be viable by means of %SWT and 82% by EDWT. Corresponding proportions of 144 segments with transmural delayed MRI contrast enhancement in acute MI were 45% and 17%. Conclusions In acute reperfused MI viable myocardium as delineated by contrast-enhanced MRI is correlated with clinical parameters of viability. Delayed MRI contrast enhancement resolves nontransmural MI and may become a valuable clinical tool when planning revascularization procedures.     

Valproic acid intoxication identified by1H and1H-13C correlated NMR spectroscopy of urine samples

Analysis of biological fluids by proton and carbon nuclear magnetic resonance spectroscopy (¹H and¹³C NMR) is a promising tool in clinical biology. We used this method for rapid toxicological screening in the case of two suicide attempts. For each case, a urine sample was analysed at 300 MHz by 1D and 2D sequences (TOCSY and HMBC) in a short experimental time. Quantification was performed by peak integration on the 1D¹H NMR spectrum. For the two patients, results showed the same resonances of the major metabolite, valproyl-O-glucuronide at concentrations of 121 and 44 mmol/l.     

On the correlation between T<Subscript>2</Subscript> and tissue diffusion coefficients in exercised muscle: quantitative measurements at 3T within the tibialis anterior

PURPOSE: To assess the transverse relaxation time T(2) and diffusion coefficient D before and following exercise in the tibialis anterior muscle and determine whether T(2) and D values were correlated. METHODS: Measurements of T(2) and D were performed at 3 T within axial slices through the calf muscles of six healthy volunteers at 95 s intervals before and for 10-12 min after a dorsiflexion exercise to exhaustion. RESULTS: The mean +/- standard deviation (SD) of T(2) and D before exercise were 32 +/- 1.55 ms and 1.52 +/- 0.15 mum(2)/ms, and after exercise were 43 +/- 2.5 ms and 1.72 +/- 0.13 mum(2)/ms, respectively. The mean +/- SD inter-individual recovery times of the % change in T(2) and D after exercise were 7.9 +/- 4.2 and 10.9 +/- 7.0 min, respectively. The T(2) and D values showed a significant correlation throughout the experiments (r (2) = 0.45). CONCLUSIONS: The increase in T(2) of skeletal muscle after exercise is correlated with the increase of the diffusion coefficient D and the recovery times appear similar, indicating that any model used to explain T(2) increases with exercise must also account for increased diffusion coefficients.     

Validation of glutathione quantitation from STEAM spectra against edited 1H NMR spectroscopy at 4T: application to schizophrenia

Objective: Quantitation of glutathione (GSH) in the human brain in vivo using short echo time ¹ H NMR spectroscopy is challenging because GSH resonances are not easily resolved. The main objective of this study was to validate such quantitation in a clinically relevant population using the resolved GSH resonances provided by edited spectroscopy. A secondary objective was to compare several of the neurochemical concentrations quantified along with GSH using LCModel analysis of short echo time spectra in schizophrenia versus control. Materials and Methods: GSH was quantified at 4T from short echo STEAM spectra and MEGA-PRESS edited spectra from identical volumes of interest (anterior cingulate) in ten volunteers. Neurochemical profiles were quantified in nine controls and 13 medicated schizophrenic patients. Results: GSH concentrations as quantified using STEAM, 1.6 ± 0.4 μmol/g (mean ± SD, n=10), were within error of those quantified using edited spectra, 1.4 ± 0.4 μmol/g, and were not different (p=0.4). None of the neurochemical measurements reached sufficient statistical power to detect differences smaller than 10% in schizophrenia versus control. As such, no differences were observed. Conclusions: Human brain GSH concentrations can be quantified in a clinical setting using short-echo time STEAM spectra at 4T.     

The role of relaxation time corrections for the evaluation of long and short echo time <Superscript>1</Superscript>H MR spectra of the hippocampus by NUMARIS and LCModel techniques

1H MR spectroscopy is routinely used for lateralization of epileptogenic lesions. The present study deals with the role of relaxation time corrections for the quantitative evaluation of long (TE=135 ms) and short echo time (TE=10 ms) 1H MR spectra of the hippocampus using two methods (operator-guided NUMARIS and LCModel programs). Spectra of left and right hippocampi of 14 volunteers and 14 patients with epilepsy were obtained by PRESS (TR/TE=5000/135 ms) and STEAM (TR/TE=5000/10 ms) sequences with a 1.5-T imager. Evaluation was carried out using Siemens NUMARIS software and the results were compared with data from LCModel processing software. No significant differences between the two methods of processing spectra with TE=135 ms were found. The range of relaxation corrections was determined. Metabolite concentrations in hippocampi calculated from spectra with TE=135 ms and 10 ms after application of correction coefficients did not differ in the range of errors and agreed with published data (135 ms/10 ms: NAA=10.2±0.6/10.4±1.3 mM, Cho=2.4±0.1/2.7±0.3 mM, Cr=12.2±1.3/11.3±1.3 mM). When relaxation time corrections were applied, quantitative results from short and long echo time evaluation with LCModel were in agreement. Signal intensity ratios obtained from long echo time spectra by NUMARIS operator-guided processing also agreed with the LCModel results.     

Creatine loading and resting skeletal muscle phosphocreatine flux: a saturation-transfer NMR study

³¹P saturation-transfer nuclear magnetic resonance spectroscopy was used to study skeletal muscle phosphocreatine (PCr) flux in healthy male volunteers. Data analysis included consideration of effects from incomplete saturation and radiofrequency spillover. Spectra were recorded from the resting gastrocnemius muscle before and after 6 days of creatine monohydrate (Cr·H₂O) intake (20 g/day). Parallel to an improved muscle performance during maximal intermittent exercise following Cr·H₂O supplementation, the concentration of PCr increased(P = 0.01) by 23% (34.9 ± 2.8 mmol/ 1 vs. 28.6 + 2.7 mmol/1), whereas other metabolites were unaffected (inorganic phosphate: 4.3± 1.4 mmol/1, free intracellular Mg²⁺: 1.1 ±0.7 mmol 1, cytosolic pH: 7.04 ± 0.02). Forward and reverse fluxes through the creatine kinase (CK) reaction did not change significantly from their baseline levels (v_for: 11.8 ± 5.4 mmol/1 per second vs. 15.3 ± 6.8 mmol 1 per second. (v_rev: 9.5 ± 3.4 mmol/1 per second vs. 10.9 ± 3.7 mmol/ 1 per second). The rate of PCr resynthesis in resting muscle is not limited by the CK reaction, which is near equilibrium. Consequently, the post-load increase in total creatine has no effect on the unidirectional CK reaction rates.     

Estimation of metabolite <Emphasis Type="Italic">T</Emphasis><Subscript>1</Subscript> relaxation times using tissue specific analysis,signal averaging and bootstrapping from magnetic resonance spectroscopic imaging data

Object A novel method of estimating metabolite T ₁ relaxation times using MR spectroscopic imaging (MRSI) is proposed. As opposed to conventional single-voxel metabolite T ₁ estimation methods, this method investigates regional and gray matter (GM)/white matter (WM) differences in metabolite T ₁ by taking advantage of the spatial distribution information provided by MRSI. Material and methods The method, validated by Monte Carlo studies, involves a voxel averaging to preserve the GM/WM distribution, a non-linear least squares fit of the metabolite T ₁ and an estimation of its standard error by bootstrapping. It was applied in vivo to estimate the T ₁ of N-acetyl compounds (NAA), choline, creatine and myo-inositol in eight normal volunteers, at 1.5 T, using a short echo time 2D-MRSI slice located above the ventricles. Results WM-T _1,NAA was significantly (P < 0.05) longer in anterior regions compared to posterior regions of the brain. The anterior region showed a trend of a longer WM T ₁ compared to GM for NAA, creatine and myo-Inositol. Lastly, accounting for the bootstrapped standard error estimate in a group mean T ₁ calculation yielded a more accurate T ₁ estimation. Conclusion The method successfully measured in vivo metabolite T ₁ using MRSI and can now be applied to diseased brain.     

Impact of prenatal stress on <Superscript>1</Superscript>H NMR-based metabolic profiling of rat amniotic fluid

Object  

The impact of inflammation in utero on amniotic fluid composition, the delivery term and the number of newborn rats per litter was investigated. The growth of newborns during the first fourteen days of life was analysed.     

Measurements of T1 and T2 relaxation times of colon cancer metastases in rat liver at 7 T

The purpose of this study was to investigate the magnetic resonance imaging (MRI) characteristics of colon cancer metastases in rat liver at 7 T. A dedicated RF microstrip coil of novel design was built in order to increase the signal-to-noise ratio and, in combination with respiratory triggering, to minimize motion artifacts. T₁- and T₂-weighted MR imaging was performed to follow tumor growth. T₁-weighted images provided a good anatomical delineation of the liver structure, while the best contrast between metastases and normal liver tissue was achieved with T₂-weighted images.Measurements of T₁ and T₂ relaxation times were performed with inversion recovery FLASH and Carr–Purcell–Meiboom–Gill and inversion recovery FLASH imaging sequences, respectively, for quantitative MR characterization of metastases. Both the T₁ and T₂ of the metastases were significantly higher than those of normal liver tissue. Further, an increase in the T₁ relaxation time of the metastases was observed with tumor growth. These findings suggest that quantitative in vivo MR characterization provides information on tumor development and possibly response to therapy, though additional studies are needed to elucidate the correlation between the changes in relaxation times and tumor microenvironment.     

In vivo MR investigation of skeletal muscle function in small animals

In vivo ³¹P-MRS investigations have been widely used in small animals to study skeletal muscle function under normal and pathological conditions. Paradoxically in these studies, the benefit provided by ³¹P-MRS in terms of non-invasiveness is lost because of the utilization of experimental setups that integrate invasive devices for inducing muscle contractions and for measuring mechanical performance. These traditional methodologies, which require surgical preparations, have obvious limitations regarding repeatability in the same animal. The purpose of this review is to highlight the technical aspects of the in vivo MR investigations of skeletal muscle function in small animal models. We will more particularly address the issue related to the invasiveness of different procedures used so far in order to show finally that a further step into non-invasiveness can be achieved, in particular with the support of muscle functional ¹H-MRI.     

<Superscript>1</Superscript>H-MRS of brain metabolites in migraine without aura: absolute quantification using the phantom replacement technique

Objective   

Several studies have demonstrated differences in migraine patients when performing ¹H-MRS; however, no studies have performed ¹H-MRS in migraine without aura (MwoA), the most common migraine subtype. The aim of this ¹H-MRS study was to elucidate whether any differences could be found between MwoA patients and controls by performing absolute quantification.     

Hyperpolarized <Superscript>3</Superscript>He lung ventilation imaging with <Emphasis Type="Italic">B</Emphasis><Subscript>1</Subscript>-inhomogeneity correction in a single breath-hold scan

The signal-to-noise ratio (SNR) of hyperpolarized noble gas MR images is sensitive to the flip angle used. Variations in flip angle due to B ₁-inhomogeneity of the RF coil cause intensity variation artifacts in lung ventilation images which may mask or mimic disease. We show these artifacts can be minimized by using the optimal flip angle and corrected if the local flip angle is known. Hyperpolarized ³He lung images were obtained in ten healthy subjects using both a conventional gradient-echo sequence and a new hybrid pulse sequence designed to simultaneously acquire lung ventilation images and corresponding flip-angle maps in comparable imaging time. Flip-angle maps and corrected images were calculated from the hybrid scan and compared with conventional images. The qualitative theoretical dependence of flip angle on SNR was verified. Ventilation images and flip-angle maps were successfully obtained with the hybrid sequence. Corrections to image intensity calculated from the flip-angle maps appeared reasonable for images acquired using an average flip angle near optimal. Use of the optimal flip angle is crucial to the quality of lung ventilation images. Artifactual intensity variations due to RF-coil inhomogeneity may be identified and potentially corrected using our hybrid sequence. Acknowledgement The authors thank John M. Christopher, RT(R)(MR) for valuable assistance performing the studies, and Jaime F. Mata, MS, Jing Cai, MS, and Andrew G. Reish, BS, for excellent operation of the ³He polarization system. We gratefully acknowledge support for this research from the Commonwealth of Virginia Technology Research Fund (Grant No. IN2002-01), Siemens Medical Solutions and Amersham Health.     

Dynamic interleaved 1H/31P STEAM MRS at 3 Tesla using a pneumatic force-controlled plantar flexion exercise rig

Objective: To develop a measurement method for interleaved acquisition of ¹H and ³¹ STEAM localised spectra of exercising human calf muscle. Materials and Methods: A non-magnetic exercise rig with a pneumatic piston and sensors for force and pedal angle was constructed to enable plantar flexion measured in the 3 T MR scanner, which holds the dual tuned (¹H ,³¹P) surface coil used for signal transmission and reception. Results: ³¹ spectra acquired in interleaved mode benefit from higher Signal to noice ratio (factor of 1.34 ±0.06 for PCr) compared to standard acquisition due to the Nuclear Overhauser effect and substantial PCr/P_i changes during exercise can be observed in ³¹P spectra. ¹H spectral quality is equal to that in single mode experiments and allows Cr2 changes to be monitored. Conclusion: The feasibility of dynamic interleaved localised ¹H and ³¹P spectroscopy during plantar flexion exercise has been demonstrated using a custom-built pneumatic system for muscle activation. This opens the possibility of studying the dynamics of metabolism with multi nuclear MRS in a single run.     

Signal enhancement through heteronuclear polarisation transfer in in-vivo <Superscript>31</Superscript>P MR spectroscopy of the human brain

Significant ³¹P NMR signal enhancement through heteronuclear polarisation transfer was obtained in model solutions and in vivo on a 1.5-T whole-body MR scanner equipped with two RF channels. The much higher population differences involved in proton Zeeman energy levels can be transferred to the ³¹P levels with the refocused INEPT (insensitive nucleus enhancement by polarisation transfer) double-resonance experiment by means of a series of simultaneously applied broadband RF pulses. INEPT achieves a polarisation transfer from ¹H to ³¹P spin states by directly reordering the populations in spin systems with heteronuclear scalar coupling. Thus, only the ³¹P NMR signal of metabolites with scalar ¹H–³¹P coupling is amplified, while the other metabolite signals in the spectra are suppressed. Compared to Ernst-angle excitation, a repetition-time-dependent signal enhancement of η=(29±3)% for methylene diphosphonic acid (MDPA) and η=(56±1)% for phosphorylethanolamine (PE) was obtained on model solutions through optimisation of the temporal parameters of the pulse experiment. The results are in good agreement with numerical calculations of the theoretical model for the studied spin systems. With optimised echo times, in-vivo ³¹P signal enhancement of the same order was obtained in studies of the human brain.