Wulf-Ingo Jung

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.

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).

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.

Cardiac energetics correlates to myocardial hypertrophy in Friedreich's ataxia.

Friedreichs ataxia is a neurodegenerative disease frequently associated with hypertrophic cardiomyopathy. We have determined mitochondrial ATP, phosphocreatine, and intracellular inorganic phosphate levels by 31P nuclear magnetic resonance spectroscopy in the heart of 11 Friedreichs ataxia patients and 11 healthy controls. For the first time, to our knowledge, we showed a significant correlation between the extent of myocardial energy deficiency and the degree of myocardial hypertrophy. When combining our results with previous works on Friedreichs ataxia, these novel findings suggest that energy metabolism is most likely the cause and hypertrophy the effect in Friedreichs ataxia. Ann Neurol 2003;53:000–000

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.

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.

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.

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.