Wolfgang Hänicke

Localized proton spectroscopy using stimulated echoes

This paper describes a new method for spatially resolved NMR spectroscopy that takes advantage of stimulated echo signals. STEAM (stimulated echo acquisition mode) sequences, already used for a variety of imaging purposes, almost perfectly match the requirements of image-controlled localized 1H NMR in vivo. Superior spatial discrimination as well as high flexibility with respect to location, size, and shape of the volume of interest is achieved by employing only three slice-selective 90° rf pulses in the presence of orthogonal gradients. The method is a single-step procedure minimizing rf power requirements and gradient switches. It further allows accurate determinations of localized T1 and T2 relaxation times simply by varying the length of corresponding intervals of the STEAM sequence. In fact, the inherent T2 weighting may be used for water suppression and/or reduction of residual eddy current effects. Here we present first results on phantoms and human extremities demonstrating the ease of image selection, localized spectroscopy, and localized determinations of relaxation times. Future steps will deal with water/lipid-suppressed metabolic spectroscopy.

Creatine deficiency in the brain: a new, treatable inborn error of metabolism.

ABSTRACT: In a patient with extrapyramidal movement disorder and extremely low creatinine concentrations in serum and urine, in vivo proton magnetic resonance spectroscopy disclosed a generalized depletion of creatine in the brain. Oral substitution of arginine, a substrate for creatine synthesis, resulted in an increase of brain guanidinoacetate as the immediate precursor of creatine but did not elevate cerebral creatine levels. In contrast, oral substitution of creatine-monohydrate led to a significant increase of brain creatine, a decrease of brain guanidinoacetate, and a nor-malization of creatinine in serum and urine. Phosphorus magnetic resonance spectroscopy of the brain revealed no detectable creatine-phosphate before oral substitution of creatine and a significant increase afterward. Partial restoration of cerebral creatine concentrations was accompanied by improvement of the patients neurologic symptoms. This is the first report of a patient with complete creatine deficiency in the brain. Magnetic resonance spectroscopy during arginine and creatine treatment point to an inborn error of creatine biosynthesis at the level of guanidinoacetete-methyltransferase.

Self-diffusion NMR imaging using stimulated echoes

Abstract NMR imaging of molecular self-diffusion is demonstrated for the first time using stimulated-echo (STE) NMR signals. Stimulated-echo acquisition-mode (STEAM) imaging has been described in a preceding paper. It is based on a 90°-t1-90°-t2-90°-t3 rf excitation sequence and relies on the detection of the STE signal appearing at t3 = t1. By incorporating a pair of pulsed magnetic field gradients into the first and third intervals of the STEAM sequence, the effect of molecular self-diffusion on NMR images may be qualitatively demonstrated. A variation of the strength of the gradient pulses and/or the diffusion time, i.e., the length of the second interval, yields a series of diffusion weighted images which allows the calculation of a synthetical image solely displaying the self-diffusion coefficient. Experimental results on 1H NMR images of phantoms are presented which clearly demonstrate the potential of diffusion imaging as a new tool in medical diagnosis as well as for nonmedical applications.

Stimulated echo imaging

Abstract A new form of NMR imaging is described using stimulated echoes. The technique, dubbed STEAM ( sti mulated e cho acquisition m ode) imaging, turns out to become a versatile tool for multipurpose NMR imaging. Stimulated echoes can be excited by a sequence of at least three rf pulses, which in the basic experiment have flip angles of 90° or less. Thus no selective or nonselective 180° pulses are needed, which eliminates a variety of problems associated with such pulses in conventional spin-echo NMR imaging. Further advantages of STEAM imaging are concerned with the functional flexibility of an imaging sequence comprising three pulses and three intervals and the possibility of “storing” information prepared during the first interval into the form of longitudinal magnetization during the second interval. In general, the applied rf power is considerably reduced as compared to spin-echo-based imaging sequences. Here the general principles of the technique are outlined and first applications to multislice imaging of directly neighboring slices are demonstrated. Subsequent papers will be concerned with modifications of the basic STEAM sequence which, for example, allow multiple chemical-shift-selective (CHESS) imaging, complete imaging of the spin-lattice relaxation behavior, diffusion imaging, and single-shot real-time imaging.

Localized proton NMR spectroscopy of brain tumors using short-echo time STEAM sequences.

Recent progress in localized proton NMR spectroscopy has been utilized to improve the spatial resolution and the metabolic specificity in a study of 19 patients with intracranial tumors. Selected examples demonstrate that short echo time stimulated echo acquisition mode sequences are able (a) to account for macroscopic tissue heterogeneity by reducing the volume of interest to 2-8 ml and (b) to facilitate a reasonable characterization of tumor metabolism by increasing the number of accessible metabolites. Proton NMR spectra were acquired within measuring times of 6.5 min on a 2.0 T whole-body system using the imaging headcoil.

The Effect of Acetazolamide on Regional Cerebral Blood Oxygenation at Rest and under Stimulation as Assessed by MRI

The sensitivity of gradient echo magnetic resonance imaging (MRI) to changes in cerebral blood oxygenation (CBO) has been introduced for mapping functional brain activation. Here, we report that this approach allows monitoring autoregulation in the human brain under vasodilatory stress. Following the administration of acetazolamide, signal intensities of deoxyhemoglobin-sensitive images increased in cortical and subcortical gray matter and to a lesser extent in white matter. This result reflects a venous hyperoxygenation stemming from an increase in cerebral perfusion with oxygen consumption remaining constant. In addition, pharmacologic induction of vasodilation attenuated activity-related MRI signal changes in the visual cortex under photic stimulation. Although intersubject variability was high, this finding indicates individually persisting autoregulatory responsiveness to functional challenge despite an “exhausted” reserve capacity. It is suggested that recording CBO by MRI will foster our understanding of modulation of vasomotor tone and cerebral perfusion. Furthermore, this technique may prove valuable for assessing the cerebrovascular reserve capacity in patients with carotid artery occlusive disease.

Alterations of brain metabolites in metachromatic leukodystrophy as detected by localized proton magnetic resonance spectroscopy in vivo

The brain morphology and chemistry of seven children with late infantile (4/7) and juvenile (3/7) forms of metachromatic leukodystrophy (MLD) were investigated by magnetic resonance imaging (MRI) and localized proton magnetic resonance spectroscopy (MRS). Patients who were examined at least 6 months after the onset of symptoms (6/7) had severe leukodystrophic changes on MRI. Proton MRS revealed a marked reduction of the neuronal markerN-acetylaspartate in white and grey matter and elevated lactate in demyelinated areas. In contrast to other leukodystrophies MLD patients showed a generalized increase of brainmyo-inositol (2- to 3-fold in white matter), indicating a specific role in the pathophysiology of demyelination in MLD.

Transverse coherence in rapid FLASH NMR imaging

Abstract FLASH ( f ast low-angle shot ) imaging is a rapid NMR imaging technique using radiofrequency pulses with flip angles of less than 90° and detection of the FID signal in the form of a gradient-recalled echo. Although in vivo applications of the sequence basically rely on a steady state of the longitudinal magnetization, tissues with long spin-spin relaxation times T 2 may lead to the establishment of a steady-state transverse magnetization: residual transverse magnetizations at the end of the repetition interval are transformed into a SSFP-like signal by subsequent rf pulses. Interference of these transverse coherences with the FID or gradient echo leads to image artifacts. Here we propose two modifications of the basic FLASH sequence that either eliminate (“spoil”) or include (“refocus”) the effects of transverse coherences in rapid images. Experiments have been carried out on phantoms using a 2.35 T 40 cm magnet (Broker Medspec) and on healthy volunteers using a 1.5 T whole-body system (Siemens Magnetom).

The influence of experimental parameters in surface-coil NMR

Abstract The experimental conditions for surface-coil applications in biomedical NMR are considered in detail. It is shown that the sensitivity as well as the spatial discrimination of a surface coil depend on the coil geometry, the radiofrequency pulse length, the pulse repetition time, and the NMR relaxation times. To simulate practical situations the sensitivity per unit time obtained from selected volumes of interest within the sensitive area of a surface coil has been calculated. Although the single-pulse surface-coil experiment yields good signal-to-noise ratios, it cannot provide spatial selectivity. In cases where “focusing” on deep-lying organs is desired, the large unwanted signal contributions from surrounding tissues have to be reduced or separated using additional techniques.

Rapid NMR imaging using stimulated echoes

Abstract Rapid NMR imaging with measuring times of the order of 200 ms (32 × 64 pixels) to 1 s (128 × 128 pixels) is demonstrated for the first time using a superconducting magnet supplied with a commercial gradient system. The technique is a simple extension of STEAM ( st imulated e cho a cquisition m ode) imaging recently presented in this journal. In the basic 90°- t 1 -90°- t 2 -90°- t 3 STEAM experiment, a single stimulated echo (STE) is recorded at t 3 = t 1 . For rapid imaging the final part of the sequence, i.e., the 90°- t 3 (STE) period, is replaced by a series of acquisition periods with small angle pulses. Each of these pulses “reads” only a small part of the longitudinal magnetization prepared by the two leading 90° pulses. Application of a different phase-encoding gradient for each STE signal yields, after Fourier transformation, a series of projections sufficient for reconstruction of an image using a standard 2D FT algorithm. Since the entire acquisition time of the rapid STEAM imaging sequence is limited only by the T 1 relaxation process, and since further the rf power deposition is considerably lower than for a multiple spin-echo sequence, the method is particularly suitable for high-field NMR imaging. 1 H images of phantoms and human extremities have been obtained at 100 MHz using a 2.3 T magnet with a bore of 40 cm.