31P nuclear magnetic resonance spectroscopy: a noninvasive tool to monitor metabolic abnormalities in left ventricular hypertrophy in human.

31p nuclear magnetic resonance (NMR) spectroscopy represents a unique instrument to noninvasively monitor myocardial metabolism in humans. The technique has been used to study the metabolism in myocardial hypertrophy in humans with hypertension, aortic stenosis, aortic incompetence, mitral regurgitation, and hypertrophic cardiomyopathy, as well as after maintenance dialysis or long-term physical exercise in elite cyclists. A primary aim is the determination of the phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio, which reflects the energetic state of the myocardium. Recent investigations take advantage of proton decoupling in 31p NMR spectroscopy, which, besides the PCr/ATP ratio, also allows the determination of the inorganic phosphate/ PCr and the phosphomonoester/PCr ratios as additional indicators for alterations in myocardial metabolism. Abnormal myocardial metabolism was found in humans with aortic stenosis, mitral regurgitation, hypertrophic cardiomyopathy, and in patients who undergo maintenance dialysis. A trend toward a lower PCr/ATP ratio was reported in hypertension and aortic incompetence patients. Several studies have revealed a dependence of the metabolic abnormalities on the degree of heart failure, and one study claimed that a correlation with the extent of hypertrophy exists. No metabolic abnormalities were found in elite cyclists.

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.

Quantitative evaluation of the lactate signal loss and its spatial dependence in press localized (1)H NMR spectroscopy.

Localized (1)H NMR spectroscopy using the 90 degrees -t(1)-180 degrees -t(1)+t(2)-180 degrees -t(2)-Acq. PRESS sequence can lead to a signal loss for the lactate doublet compared with signals from uncoupled nuclei which is dependent on the choice of t(1) and t(2). The most striking signal loss of up to 78% of the total signal occurs with the symmetrical PRESS sequence (t(1)=t(2)) at an echo time of 2/J (approximately 290 ms). Calculations have shown that this signal loss is related to the pulse angle distributions produced by the two refocusing pulses which leads to the creation of single quantum polarization transfer (PT) as well as to not directly observable states (NDOS) of the lactate AX(3) spin system: zero- and multiple-quantum coherences, and longitudinal spin orders. In addition, the chemical shift dependent voxel displacement (VOD) leads to further signal loss. By calculating the density operator for various of the echo times TE=n/J, n=1, 2, 3,..., we calculated quantitatively the contributions of these effects to the signal loss as well as their spatial distribution. A maximum signal loss of 75% can be expected from theory for the symmetrical PRESS sequence and TE=2/J for Hamming filtered sinc pulses, whereby 47% are due to the creation of NDOS and up to 28% arise from PT. Taking also the VOD effect into account (2 mT/m slice selection gradients, 20-mm slices) leads to 54% signal loss from NDOS and up to 24% from PT, leading to a maximum signal loss of 78%. Using RE-BURP pulses with their more rectangular pulse angle distributions reduces the maximum signal loss to 44%. Experiments at 1.5 T using a lactate solution demonstrated a maximum lactate signal loss for sinc pulses of 82% (52% NDOS, 30% PT) at TE=290 ms using the symmetrical PRESS sequence. The great signal loss and its spatial distribution is of importance for investigations using a symmetrical PRESS sequence at TE=2/J.

Detection of phosphomonoester signals in proton-decoupled 31P NMR spectra of the myocardium of patients with myocardial hypertrophy.

Proton-decoupled 31P NMR spectroscopy at 1.5 T of the anterior left ventricular myocardium was used to monitor myocardial phosphate metabolism in asymptomatic patients with hypertrophic cardiomyopathy (HCM, n = 14) and aortic stenosis (AS, n = 12). In addition to the well-known phosphorus signals a phosphomonoester (PME) signal was detected at about 6.9 ppm in 7 HCM and 2 AS patients. This signal was not observed in the spectra of normal controls (n = 11). We suggest that in spectra of patients with myocardial hypertrophy the presence of a PME signal reflects alterations in myocardial glucose metabolism.

Localized Larmor frequency-guided fat and water proton MRI of the spine: a method to emphasize pathological findings.

A measurement protocol providing a correct adjustment of the irradiation frequencies for well separated fat and water images of the lumbar spine is presented. To determine accurately the Larmor frequencies of water and fat protons within the vertebral bodies, a volume selective spectrum of a volume element (13 mm)3 located in a lumbar vertebral body was acquired with the 90 degrees-180 degrees-180 degrees double spin-echo method. These Larmor frequencies are used to adjust the frequency-selective pulse of the SENEX chemical-shift imaging sequence. This procedure provides well separated fat and water images for a large field of view even in the inhomogeneous region of the vertebral column. Their clinical importance is demonstrated by localized Larmor frequency-guided (LLFG) SENEX 1H images of the lumbar spine in healthy persons of different age and in a patient with acute myeloid leukemia.

Localized in vivo 1H spectroscopy of human skeletal muscle: normal and pathologic findings.

To obtain high signal to noise ratio in small volume elements (8 cm3), in vivo 1H NMR spectroscopy of normal and diseased human skeletal muscle was performed using a double spin-echo localization method on a 1.5-T whole body system. High resolved spectra of normal calf muscle show the well known resonances of lipids (methyl, methylene, olefinic, and other fatty acid resonances), creatine/phosphocreatine, choline/carnitine, taurine, and histidine with good intraindividual reproducibility. Pronounced intraindividual differences in the lipid range were found between different upper thigh muscle groups. On pathologic conditions like myopathy, myositis or irradiation damage the spectral lipid content was increased. Three months after local irradiation of the medial vastus muscle (50 Gy), the localized 1H NMR spectrum showed a complete loss of the choline and creatine signals. In a case of M. Behçet with muscular involvement the relative reduction of the choline signal may provide an insight in the pathobiochemistry. The results of our investigations in nine healthy volunteers and three patients are presented in detail including relaxation times of the metabolites.

MRI and determination of T1 and T2 of solid polymers using a 1.5 T whole-body imager.

Spin-echo sequences with echo times as short as 3.5 msec were implemented on a standard 1.5 T NMR whole-body imager for 1H imaging of polymers in the solid-state. No modification of the NMR hardware designed for clinical usage was made. Beside images of different polymers a "self-portrait" of the polymeric materials of the receiver coil is given as a neat application. Based on imaging experiments the longitudinal and transverse relaxation time of polymers were investigated. The results indicate that using a standard whole-body imager, it is possible to provide additional information to other examination techniques in polymer and materials science.

Spin-echo methods for the determination of 31P transverse relaxation times of the ATP NMR signals in vivo.

31P magnetic resonance spectroscopy (MRS) examinations of the calf muscles of healthy volunteers were performed to determine T2 of the coupled ATP signals by use of the Hahn spin-echo and the frequency-selective spin-echo method. Additional measurements with the J-coupling refocused double echo are presented. The most reliable determination of T2 relaxation times is possible with the frequency-selective spin echo. The other methods yield substantially wrong results. Theoretical explanations are given how J-coupling and pulse-angle deviations affect the signals and therefore the T2 determinations. The calculations for a weakly coupled homonuclear AX spin system are shown because they demonstrate most of the relevant facts. In addition, some important results for a homonuclear AMX spin system, which the ATP is considered to be, are given.

31P/1H WALTZ-4 broadband decoupling at 1.5 T: different versions of the composite pulse and consequences when using a surface coil.

Two derivatives of the wideband alternating-phase low-power technique for zero-residual splitting (WALTZ)-4 decoupling sequence for broadband decoupling named WALTZ-4a and WALTZ-4b were compared for their proton decoupling performance in 31P nuclear magnetic resonance (NMR) spectroscopy using a Siemens Magnetom SP 1.5 T whole-body imager. Version WALTZ-4a originally implemented by the manufacturer doubles and triples the transmitter amplitude of the 90 degrees pulse to achieve the 180 degrees and 270 degrees flip angle required for one composite pulse R in the WALTZ sequence. WALTZ-4b follows the sequence reported from Shaka et al. and leaves the transmitter amplitude constant but increases the durations of the 180 degrees and 270 degrees pulses. The decoupling performance of WALTZ-4b is superior because it requires less transmitter power and, therefore, it is advantageous in all in vivo studies where a low specific absorption rate is desired. When WALTZ-4 is used in combination with a surface coil for transmission the theoretically required flip angles cannot be achieved in the entire sensitive volume of the coil. The decoupling performance was therefore investigated at lower and higher flip angles. Again, WALTZ-4b is advantageous and provides, in certain ranges that are off-resonant from the decoupling frequency, a good decoupling quality even for flip angles that are only 60% of the theoretically required.

Localized phosphorus NMR spectroscopy: a comparison of the FID, DRESS, CRISIS/CODEX, and STEAM methods in vitro and in vivo using a surface-coil.

The FID, DRESS, CRISIS/CODEX, and STEAM techniques for localized 31P NMR spectroscopy were compared using a Siemens Magnetom SP63 1.5 T whole-body imager and a surface-coil, 80 mm in diameter, acting as transmitter and receiver coil. The comparison was performed with phantom experiments and human in vivo investigations on the calf muscle. The phantom experiments which used the same volume size showed a comparable signal-to-noise ratio for FID and DRESS, while the two fully localized techniques showed a reduction in signal-to-noise ratio to 76% for CRISIS/CODEX and 31% for STEAM. The in vivo measurements confirm the phantom results and reveal that CRISIS/CODEX gains a 2.5 fold higher signal-to-noise ratio than STEAM under the same conditions.

Imaging of the human cardiovascular system using the rapid echo flow-rephased spin-echo technique.

Using a flow-rephased spin-echo technique with a short echo time of TE = 9.7 msec, "white blood" multislice and single slice first echo images of the human heart were acquired using standard 1.5 T whole-body imagers. The technique almost completely eliminates phase shifts for flow with constant velocity and constant acceleration, so the investigations with healthy volunteers show images which are almost free of the artifacts often found in ECG-gated standard spin-echo imaging of the heart. T1-weighted images with good contrast between tissue and blood are achieved at any time during the whole heart cycle. The results obtained indicate that the technique might be helpful for imaging small vessels, vessels which contain slowly flowing blood, and vessels located in regions with static field inhomogeneities, for example, lung vessels.

[Special MR methods for primary bone tumors: I. Chemical shift selective imaging]. / Spezielle MR-Methoden bei primären Knochentumoren: I. Chemical-shift-selektive Bildgebung.

The value of selective imaging of fat and water compared with proton density, T1- and T2- weighted MR sequences was studied in the course of 32 examinations on 22 primary bone tumours in various parts of the body. Fat selective images showed practically signal free areas for osteogenic tumours which could be distinguished from surrounding fat containing soft tissues. Water selective images improved definition of the tumour margin from oedema in the bone marrow. Chemical shift artefacts are avoided by these methods and therefore fat and water selective images provide better spatial resolution for identical pixel sizes.

[Special MR methods for primary bone tumors: II. Volume selective 1H-spectroscopy]. / Spezielle MR-Methoden bei primären Knochentumoren: II. Volumenselektive 1H-Spektroskopie.

The method of localised 1H MR spectroscopy was used in 19 examinations in 9 patients with primary bone tumours in order to obtain spectral signals and to determine whether these are specific for tumour classification. The spectra were obtained by a double spin echo method and the tumour tissue showed very high water content and only minor lipid and proton signals which showed J-coupling characteristics. The latter are not found in normal bone marrow and are probably due to products of tumour metabolism. The resolution of the spectra within a 13 mm or 20 mm tissue cube depends largely on the structural homogeneity of the tumour. The signal patterns in the spectra were not specific to histological tumour types.

Noninvasive blood flow measurement and quantification of shunt volume by cine magnetic resonance in congenital heart disease. Preliminary results.

Based on the phase difference method as described by Nayler et al. we developed a gradient-echo sequence, which refocuses flow related phase shifts even for infants with their higher peak velocity, higher acceleration and faster heart rates. A repetition time (TR) of 15 ms provides a high temporal resolution for dynamic studies. Modification of the flow-rephasing gradient-echo sequence in slice select direction leads to a defined phase shift and the resultant phase difference images allow blood flow measurements in the great arteries and the calculation of blood volume per heart cycle (flow volume) to assess left and right ventricular stroke volume. This can also be achieved by calculation of the ventricular volume from contiguous slices of the whole heart, but, this in excessive measuring times. Both methods were applied in 6 examinations of children with congenital heart diseases (1 pulmonary sling, 1 coarctation of the aorta, 1 ventricular septal defect, 3 atrial septal defects). The age of the patients ranged from 3 months to 13.4 years (mean age 4.9 years). The regression analyses of both methods show a high correlation for systemic flow (y = -0.98 + 1.08 x, r = 0.99, SEE = 2.59 ml) and for pulmonary flow (y = -1.40 + 0.96 x, r = 0.99, SEE = 4.70 ml). The comparison of flow calculated Qp:Qs ratio and chamber size calculated Qp:Qs ratio with data obtained by heart catheterization show also a regression line close to the line of identity (y = -0.01 + 1.04 x, r = 0.98, SEE = 0.15 and y = 0.28 + 0.96 x, r = 0.81, SEE = 0.47, respectively).

[Dynamic magnetic resonance tomography in pediatric cardiology: broadening of diagnostic possibilities by flow-rephasing gradient-echo sequences]. / Dynamische Kernspintomographie in der pädiatrischen Kardiologie: Erweiterung der diagnostischen Möglichkeiten mit Hilfe einer flussrephasierten Gradientenechosequenz.

Based on the phase difference method as described by Nayler et al., we developed a gradient-echo sequence, which refocuses flow-related phase shifts. With regard to the higher peak velocity and higher acceleration in infants, we reduced the echo time (TE) to 5 ms. This is effective in rephasing the flow signals even for faster heart rates. Phase shifts are further minimized by reducing the voxel size. The slice thickness down to 2 mm also improves anatomic resolution. A repetition time (TR) of 15 ms provides high temporal resolution for dynamic studies. Modification of the flow-rephasing gradient-echo sequence allows blood flow measurements in the great arteries and the calculation of blood flow volume to assess left and right ventricular stroke volume. This can also be achieved by calculating the ventricular volume from contiguous slices of the whole heart; however, it results in excessive measuring times. Compared with conventional spin-echo techniques, anatomical analysis is improved. The size of atrial septal defects (ASD) can be measured more exactly. Small atrial or ventricular septal defects (VSD), which are not detectable on spin-echo images, are demonstrated on the gradient-echo images and semi-quantitative estimation of the pressure in the right and left ventricle can be made. Pulmonary arteries and veins are clearly differentiated from bronchial structures and are traced to subsegmental levels. Without ECG-gating, contiguous slices of interesting parts of the cardiovascular system can be obtained and successfully used for secondary angiographic reconstructions.

Localized 1H in vivo NMR spectroscopy of small-volume elements in human brain at 1.5 T.

Localized in vivo proton NMR spectra of volume elements of minimal size (13 x 13 x 13 mm3) were obtained in human brain with a whole-body imager working at 1.5-T field strength. By use of an optimized version of the 90 degrees-180 degrees-180 degrees volume selection method, well-resolved proton spectra were acquired within 9 min and a comparison of spectra with different echo times (135 and 270 ms) was possible within 20 min.

[Reproducibility of localized protein spectra with a 1.5 T whole body nuclear magnetic resonance scanner]. / Reproduzierbarkeit lokalisierter Protonenspektren mit einem 1.5 T Ganzkörper-Kernspintomographen.

The CODEX method was employed for volume selective proton NMR spectroscopy with a whole body imager in order to control the quality of reproduction with phantoms. The spectral resolution and time stability during typical measuring times are almost better than 3.10(-8) and are usually sufficient for the requirements of high resolution in vivo proton spectroscopy.

[On pathogenesis of coronary heart disease]. / Zur Pathogenese der koronaren Herzerkrankung.

Being overweight (OW) was recognized very early as a risk factor for coronary heart disease (CHD). Its significance in the pathogenesis of CHD has been strengthened by observations showing that OW is responsible for the development of diabetes, hypertension and lipid disorders due to its induction of insulin resistance (IR). Its key role has been underlined further by recent studies indicating that OW causes endothelial dysfunction via elevated serum fatty acids, which initiates the molecular events that further the process of CHD. It is, therefore, of the utmost importance to determine its roots. The most probable reason for its high incidence is due to the genetic outfit of most people which does not permit adequate adaptation of the cerebral cortex according to the environmental changes which have occured since the early days.

Volume-selective proton MRS in vertebral bodies.

Volume-selective 1H magnetic resonance spectra of small volume elements of (13 mm)3 positioned in lumbar vertebral bodies have been investigated in 15 healthy persons of different ages and sexes and in 11 patients with leukemia using double spin-echo sequences. Signal intensities and positions of the spectral lines have been evaluated. Interindividual spectra of VOI located in the center of vertebral bodies, intraindividual spectra of central VOI in different vertebral bodies, and spectra of different localizations within the same vertebral body have been compared as well as spectra before and partly after cytostatic treatment in leukemia patients. Unexpected phenomena of the signal shapes have been found. The water signal distributions in healthy persons compared to patients after bone marrow transplantation show significant differences. The success of the cytostatic treatment in cases of leukemia is accompanied by an increase in the intensity of the lipid signals and a decrease in the water signals.