Otto Lutz

31P NMR Spectroscopy Detects Metabolic Abnormalities in Asymptomatic Patients With Hypertrophic Cardiomyopathy

BACKGROUND Hypertrophic cardiomyopathy (HCM) often causes sudden, unexpected death in adolescents and young adults. Alterations in myocardial metabolism are considered to be causes for contractile dysfunction. We examined the question of whether metabolic abnormalities antedate the manifestation of symptoms in patients with HCM. METHODS AND RESULTS Proton-decoupled 31P NMR spectroscopy of the anterior left ventricular wall of the heart of 14 young, asymptomatic patients with HCM was performed with a 1.5-T whole-body imager. Spectra of the phosphate metabolites were compared with those of normal control subjects. The patients exhibited a significantly reduced (P<0.02) ratio of phosphocreatine (PCr) to ATP of 1.98+/-0.37 (mean+/-SD), compared with 2.46+/-0.53 obtained in 11 normal control subjects. In addition, the group of patients with severe hypertrophy of the interventricular septum (n=8) showed a significantly increased (P<0.05) Pi-to-PCr ratio, with a Pi x 100/PCr of 20.0+/-8.3 versus 9.7+/-7.2 in control subjects. Both abnormalities are similar to those found in ischemic myocardium. This view is also supported by a significantly increased (P<0.01) phosphomonoester (PME)-to-PCr ratio, with a PME x 100/PCr of 20.7+/-11.2 compared with 8.4+/-6.7 in control subjects, indicating altered glucose metabolism. CONCLUSIONS 31P NMR spectroscopy detects alterations of myocardial metabolism in asymptomatic patients with HCM. These alterations may contribute to the understanding of the pathophysiology and natural history of the disease.

Reliable detection of macromolecules in single-volume 1H NMR spectra of the human brain.

In short echo time proton MR spectra of the brain, resonances from macromolecules are visible. The macromolecular resonances in the 0.5–2.0 ppm region can be affected by lipid contamination arising from fat‐containing regions outside the selected volume of interest (VOI). This study demonstrates that considerable lipid contamination may remain in stimulated echo acquisition mode (STEAM) spectra even if the spoiling of unwanted coherences is sufficient and the VOI is placed 2 cm or more away from fat‐containing regions. The observed contamination was attributed to residual remote out‐of‐volume excitation, although only very small out‐of‐slice ripples of less than 0.2% of the in‐slice excitation were found in the calculated excitation profile of the RF pulses. Spatial presaturation of fat‐containing regions led to a sufficient suppression of the contamination and enabled the detection of highly reproducible macromolecular resonances. Thus, in single‐volume spectroscopy as well as in spectroscopic imaging (SI or CSI), the combination of volume selection and outer volume presaturation, each in three dimensions, is highly recommended to ensure accurate detection and reliable evaluation of even small pathological alterations in macromolecules, e.g., proteins or lipids, or other resonances in the 0.5–2.0 ppm region. Magn Reson Med 45:948–954, 2001.

Leukemic red bone marrow changes assessed by magnetic resonance imaging and localized1H spectroscopy

SummaryRed bone marrow of healthy persons has considerable contents of water and lipids. The cellularity and the corresponding fat-water ratio within the marrow show clear changes in hematological diseases. Magnetic resonance (MR) methods use the signals of the protons of water and lipids. This paper gives a comparison between different standard MR techniques and recently developed fat- and water-selective imaging methods, addressing their sensitivity to bone marrow changes in leukemia. Additionally,1H results of spectroscopic methods are presented. The results and conclusions are based on the examination of 26 healthy volunteers and 106 patients with general or focal bone marrow alterations. Standard T1-weighted images did not distinguish bone marrow of young healthy volunteers with relatively high cellularity from acute leukemia. Using fat- and water-selective methods, patients with untreated leukemia showed only water proton signals and no lipid signals from red bone marrow of vertebral bodies and the pelvis. This phenomenon was never observed in healthy volunteers. Following chemotherapy, lipid and water contents normalize in successfully treated patients. Nonresponders did not show significant changes of the fat-water ratio after up to 3 weeks of therapy. Phase contrast imaging provides information about the difference between fat and water fractions within the bone marrow, but quantitative determination of the absolute fat and water fractions requires acquisition of several images and suffers from the susceptibility effects in trabecular bone marrow. The fat-water ratio and additional qualities of water and lipid protons (relaxation times) can be evaluated by volume-selective MR spectroscopy. Typical results of spectra from small-volume elements in hypercellular vertebral bone marrow of leukemic patients before cytotoxic treatment and of normocellular or hypocellular marrow after therapy are demonstrated.

PROTON SPECTROSCOPY OF HUMAN BRAIN WITH VERY SHORT ECHO TIME USING HIGH GRADIENT AMPLITUDES

In localized proton magnetic resonance spectroscopy very short echo times (TE) are achieved to diminish signal loss due to T2 relaxation and to avoid phase distortions due to J-coupling. A sequence for single volume spectroscopy in human brain is described with a TE as low as 5 ms. Examinations were performed on a 1.5 T whole-body imager with actively shielded gradients. A self-designed stimulated echo acquisition mode (STEAM) sequence with very high amplitude spoiling gradients of 24 mT/m was used to take advantage of the whole potential of the gradient system. Optimization of TE was carried out by controlling spectral quality and localization in both phantom and volunteer measurements. Proton spectra of human brain were acquired in 21 healthy volunteers. Spectra of occipital white matter, parieto-occipital grey/white matter, and cerebellum revealed none or only small eddy current distortions at a TE of 5 ms. The volume of interest was 8-12 ml, repetition time was 1.5 s, and mixing time was 5 ms. Peak ratios of major metabolites referring to creatine were estimated and the relative standard deviations were calculated to determine interindividual reproducibility. The relative standard deviation of myo-inositol ranged from 6% to 11% within these brain regions whereas for glutamine and glutamate 7% to 16% were found.

Lactate quantification by means of press spectroscopy—Influence of refocusing pulses and timing scheme

The quantitative assessment of lactic acid in tissue is an important goal for in vivo volume-selective NMR spectroscopy to aid in the noninvasive diagnosis of oxygen deficiency of other metabolic disorders. PRESS localized 1H spectra provide comparatively high signal-to-noise ratio from small volume elements in a single acquisition mode. The quantification of lactate after multipulse excitation is not trivial due to the J-coupling characteristics which do not occur for the substances serving as references. The influence of the timing scheme and of the quality of the refocusing pulses was systematically evaluated for the lactate resonances by volume-selective measurements. Gaussian pulses, Hanning-filtered sinc pulses, and numerically optimized RE-BURP-pulses were applied for refocusing the magnetization in the PRESS sequence and the effects on the lactate AX3 spin system were compared. For these pulses, sequence parameters are presented providing high sensitivity to lactate signals. Timing schemes are shown which provide good quantification of lactate, even in cases with B1-inhomogeneities or slight misadjustment of the transmitter amplitude. The combination of both echo times in the double-echo sequences clearly influences the signal characteristics of lactate at overall echo times near TE = 145 and 290 ms, which may result in pure in-phase magnetization for this weakly coupled homonuclear system. Numerically optimized refocusing pulses (RE-BURP) provided up to 50% higher signal ratio of the methyl protons of lactate to uncoupled nuclei than the often used Hanning-filtered sinc pulses.

Localized double-spin-echo proton spectroscopy of weakly coupled homonuclear spin systems

Abstract The effect of localized double-spin-echo spectroscopy (PRESS) on a homonuclear weakly coupled AX spin system was calculated by the use of the product-operator formalism. Due to flip-angle distributions within the excited slices, different unwanted coherences are created which give rise to signal losses after the second and third RF pulse. The amount of signal loss is dependent on the timing of the sequence; i.e., only a proper choice of the time intervals between the pulses results in a high signal strength for coupled spins. Experiments were carried out on a Siemens Magnetom 1.5 T whole-body imager to verify the theory. Signal gains of far more than 100% were obtained for the coupled spins of lactate.

Proton relaxation times in human red bone marrow by volume selective magnetic resonance spectroscopy

In hematological diseases the composition of red bone marrow shows alterations. The relaxation timesT1 andT2 of water and lipids in human hemopoietic bone marrow of 14 normal volunteers and 10 patients with acute leukemia and bone marrow carcinosis are determined using a double spin echo spectroscopy sequencein vivo. The volumes of interest (VOI) of (13 mm)3 in the center of vertebral bodies are examined using different measurement parameters. ForT1 measurements an inversion-recovery method is used.T2 is evaluated from spectra with differentTE. T1 (water) is found in a range between 1000 and 1700 ms,T1 (lipids) in a range between 260 and 320 ms in healthy volunteers.T2 (water) is determined between 32 and 65 ms. In some cases phase distortions of the water signals occur in the spectra. Water flow within the VOI may be a possible reason.T2 (lipids) is evaluated between 73 and 91 ms. The patients with acute leukemia exhibit clearly reduced lipid signals in their spectra. Lipid relaxation times could not be determined in these cases.T2 (water) is prolonged in acute leukemia to 51–98 ms.T1 (water) was not significantly different from values of healthy volunteers in our measurements. Results are discussed in comparison to relaxometric data from imaging and STEAM spectroscopic methods of other authors.

Subtle bone marrow edema assessed by frequency selective chemical shift MRI

Subtle edema in yellow bone marrow from tumors (14 subjects) and osteomyelitis (9 subjects) were examined by selective nonexcitation (SENEX) water imaging using a short five pulse frequency selective excitation with lipid suppression greater than 96%. Standard spin-echo (SE) proton density-, T1- and T2-weighted images, and fat suppression methods such as short inversion time inversion recovery and also the chemical shift selective Dixon method are discussed in comparison with SENEX. Application of the SENEX method is described and images from four typical cases are demonstrated. Sensitivity to edema is obviously better using the SENEX chemical shift selective method than using other imaging techniques. Improved delineation of abnormal areas in yellow bone marrow is provided by SENEX water imaging in one slice after multislice standard imaging. After shimming, only one SE scan with frequency selective excitation is necessary to get a pure water image.

Proton-decoupled myocardial 31P NMR spectroscopy reveals decreased PCr/Pi in patients with severe hypertrophic cardiomyopathy.

Disturbed myocardial energy metabolism may occur in patients with primary hypertrophic cardiomyopathy (HCM). A noninvasive way to gain insight into cardiac energy metabolism is provided by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. 31P NMR spectroscopy with proton decoupling was performed in 13 patients aged 13-36 years with HCM on a 1.5 T Magnetom with a double resonant surface coil. A 2D chemical shift imaging (CSI) sequence in combination with slice selective excitation was used to acquire spectra of the anteroseptal region of the left ventricle (volume element: 38 mL). The chemical shifts of the phosphorus metabolites, intracellular pHi, and coupling constants J(alphabeta) and J(gammabeta) were calculated. Peak areas of 2,3-diphosphoglycerate (DPG), Pi, and adenosine triphosphate (ATP) were determined and corrected for blood contamination, saturation, and differences in nuclear Overhauser enhancements (NOE). The maximum thickness of the interventricular septum (IVSmax) was determined from tomographic long-axis images and expressed as number of standard deviations above the mean of the normal population (Z score). The patients were then divided into 2 groups: 6 patients with moderate HCM (HCMm, Z score < or = 5) and 7 patients with severe HCM (HCMs, Z score > 5). No differences between both groups and a control group of healthy volunteers (n = 16) were found with respect to phosphocreatine (PCr)/gamma-ATP ratio, pHi, or the coupling constants. Only the PCr/Pi ratio differed significantly from the control group (HCM(all), alpha < 0.05, HCMs, alpha < 0.02, 2-sided U test). The decrease of the PCr/Pi ratio in patients with HCM is probably caused by ischemically decreased oxygen supply in the severely hypertrophied myocardium.

135La and139La nuclear magnetic resonance studies

Abstract Fourier transform NMR investigations of138La and139La have been performed. Ratios of Larmor frequencies, magnetic moments, the ratio of the quadrupole moments, and a hyperfine structure anomaly for these nuclei have been determined. For139La chemical shifts and linewidths in aqueous lanthanum salt solutions, solvent isotope effects, linewidths as a function of temperature, and signals in solid state have been investigated.