Klaus-Dietmar Merboldt

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.

Simultaneous recording of cerebral blood oxygenation changes during human brain activation by magnetic resonance imaging and near-infrared spectroscopy

Changes in cerebral blood oxygenation due to functional activation of the primary sensorimotor cortex during a unilateral finger opposition task were simultaneously mapped by deoxyhemoglobin-sensitive magnetic resonance imaging (MRI) and monitored by near-infrared spectroscopy (NIRS). Activation foci along the contralateral central sulcus displayed task-associated increases in MRI signal intensity, indicating a concomitant decrease of the focal concentration of deoxyhemoglobin. This interpretation was confirmed by simultaneous reductions in deoxyhemoglobin measured optically. Since observation of the latter effect required exact spatial matching of the MRI-detected activation foci and position of the fiber optic bundles (“optodes”) used for transmitting and receiving light, it may be concluded that optical recordings of changes in deoxyhemoglobin during functional challenge probe only a restricted brain tissue region. While deoxyhemoglobin responses seen by NIRS were smaller for ipsi- than for contralateral finger movements, task-related increases in oxyhemoglobin were rather similar between both conditions and, thus, seem to be less specific. Furthermore, no consistent changes were obtained for total hemoglobin during task performance, possibly due to the short timing of the repetitive protocol. In general, results underline, in humans, the hitherto assumed signal physiology for functional brain mapping by oxygenation-sensitive MRI and allow assessment of both constraints and practicability of functional studies by NIRS.

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.

Real‐time MRI at a resolution of 20 ms

The desire to visualize noninvasively physiological processes at high temporal resolution has been a driving force for the development of MRI since its inception in 1973. In this article, we describe a unique method for real‐time MRI that reduces image acquisition times to only 20 ms. Although approaching the ultimate limit of MRI technology, the method yields high image quality in terms of spatial resolution, signal‐to‐noise ratio and the absence of artifacts. As proposed previously, a fast low‐angle shot (FLASH) gradient‐echo MRI technique (which allows for rapid and continuous image acquisitions) is combined with a radial encoding scheme (which offers motion robustness and moderate tolerance to data undersampling) and, most importantly, an iterative image reconstruction by regularized nonlinear inversion (which exploits the advantages of parallel imaging with multiple receiver coils). In this article, the extension of regularization and filtering to the temporal domain exploits consistencies in successive data acquisitions and thereby enhances the degree of radial undersampling in a hitherto unexpected manner by one order of magnitude. The results obtained for turbulent flow, human speech production and human heart function demonstrate considerable potential for real‐time MRI studies of dynamic processes in a wide range of scientific and clinical settings. Copyright

Improvements in localized proton NMR spectroscopy of human brain. Water suppression, short echo times, and 1 ml resolution

Abstract Considerable technical improvements are reported for localized proton NMR spectroscopy using stimulated echoes. When compared to previous results, proton NMR spectra of the human brain are now obtainable (i) with in vivo water suppression factors of ⩾1000, (ii) with only minor T2 losses and negligible distortions due to J modulation at short echo times of 10–20 ms, and (iii) from volumes of interest as small as 1–8 ml within measuring times of 1–10 min. As a consequence, the detection of cerebral metabolites is greatly facilitated. This particularly applies to the assignment of those resonances (e.g., glutamate, taurine, inositols) that suffer from strong spin-spin coupling at the field strengths commonly in use for NMR in man. Studies of regional metabolite differences, tissue heterogeneity, and focal lesions in patients benefit from the increased spatial resolution and a concomitant reduction of partial volume effects. Localized proton NMR spectroscopy was performed on young healthy volunteers. Experiments were carried out on a 2.0 T whole-body MRI/MRS system using the standard headcoil for both imaging and spectroscopy.

Functional MRI of the human amygdala

In view of an increasing number of publications that deal with functional mapping of the human amygdala using blood oxygenation-level-dependent (BOLD) magnetic resonance imaging, we reevaluated the underlying image quality of T2*-weighted echoplanar imaging (EPI) and fast low angle shot (FLASH) sequences at 2.0-T with regard to susceptibility-induced signal losses and geometric distortions. Apart from the timing of the gradient echoes, the degree of susceptibility influences is controlled by the image voxel size. Whereas published amygdala studies report voxel sizes ranging from 22 to 125 microl, the present results suggest that reliable imaging of the amygdala with BOLD sensitivity requires voxel sizes of 4 to 8 microl or less. Preferentially, acquisitions should be performed with a coronal section orientation. Although high-resolution BOLD MRI is at the expense of temporal resolution and volume coverage, it seems to provide the only solution to this physical problem.

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.

Proton NMR spectroscopy of cerebral metabolic alterations in infantile peroxisomal disorders.

Noninvasive studies of cerebral metabolism were performed with use of localized proton MR spectroscopy (MRS) in both healthy controls (n = 4, age 6 weeks to 2 years) and infants (n = 4, age 3-15 months) who had impaired peroxisomal functions classified as variants of Zellweger syndrome. All patients revealed a marked decrease of N-acetylaspartate in white and gray matter, thalamus, and cerebellum, indicating impairment of normal neuronal development as well as neuronal loss. In two cases an increase of cerebral glutamine and a decrease of the cytosolic polyol myo-inositol in gray matter and striatum reflected the impact of a concomitant effect on hepatic function. Two cases 3 and 6 months of age exhibited a notable elevation of mobile lipids and/or cholesterol in white matter. These patients with severe disease died within 4 weeks after the MRS examination. While an increase of free fatty acids generally associated with a lysosomal storage disease was not consistently observed by proton MRS of brain, this technique provides a convenient and safe tool for the direct assessment of neuropathologic aspects of Zellweger syndrome such as neuronal degeneration, demyelination, and consequences of compromised liver function.