Influence of brain tumors on the MR spectra of healthy brain tissue.

The neurochemical environment of nontumorous white matter tissue was investigated in 135 single voxel spectra of "healthy" white matter regions of 43 tumor patients and 129 spectra of 52 healthy subjects. Spectra were acquired with short TE and TR values. With the data of tumor patients, it was examined whether differences were caused by the tumor itself or aggressive tumor therapies as confounding factors. Comparing the spectra of both classes, an excellent differentiation was possible based on the metabolite peak of N-acetylaspartate (P ≈ 0) and myoinositol (P < 0.03). The area under curve of the receiver operating characteristic was calculated as 0.86 and 0.62, respectively. With linear discriminant analysis using combinations of integrals, a prediction was possible, whether a spectrum belonged to the patient or the healthy subject class with an overall accuracy above 80%. The confounding factors could be ruled out as source of the differences. The results show strong evidence for an influence of malignant growth on the biochemical environment of nontumorous white matter tissue. Because of the T(1) weighting, the measured differences between both classes were most likely concentration changes interfered by T(1) effects. The underlying processes will be subject of future studies.

In vivo 1H magnetic resonance spectroscopy of rat brain after valproate administration.

Previous studies have shown that valproate is detectable in vitro by 1H magnetic resonance spectroscopy (MRS) at 1.5 T, whereas in patients on valproate monotherapy, no significant dose-dependent valproate signal could be seen. To investigate whether an increased signal-to-noise ratio as provided by higher valproate doses and increased magnetic field strength would enable detection of valproate in vivo, six Wistar rats were examined using volume-selective 1H MRS at 2.34 T. The spectra were analyzed by fitting a linear superposition of the basis spectra of valproate, brain metabolites, and simulated lipid signals. The analysis revealed no significant signal contributions after valproate administration of up to 330 mg/kg body weight. To analyze how underlying mechanisms, such as potential drug interactions with macromolecules, may affect the valproate signal, additional in vitro spectra of valproate were measured before and after adding albumin. The spectra exhibited a strong decrease of the valproate signal with increasing albumin concentration. The results support the hypothesis that in vivo valproate is bound to a high degree to macromolecules and will therefore not be detectable by 1H MRS.

Magnetic resonance imaging studies with cluster algorithm for characterization of brain edema after controlled cortical impact injury (CCII).

Objective of this study was the characterization of traumatic brain injury induced by a "Controlled Cortical Impact" with magnetic resonance imaging techniques. The impact was applied to the intact dura of the left hemisphere in Sprague-Dawley rats. The pneumatic impactor was accelerated to a velocity of 7 m/s contusing the left temporo-parietal hemisphere to a depth of 2 mm. Posttraumatic hemispheric swelling and water content were determined gravimetrically, Evans Blue extravasation photometrically, and volume of ischemia by TTC-staining and planimetry. Magnetic resonance imaging was performed by a Bruker biospec 24/40, 90 min, 24 and 72 h post trauma using a T2w RARE sequence, a T1w sequence, before and after application of contrast agent, and a set of diffusion weighted images for calculation of ADC-maps. Data analysis was performed using a cluster algorithm enabling to interpret corresponding image pairs simultaneously. T2w imaging indicates the maximum edema about 24 h post trauma. Blood-brain barrier damage, detected by T1w imaging, is more predominant in the early posttraumatic phase. The cluster algorithm detects different edema components: from the necrotic core to the perifocal vasogenic rim. MRI in combination with the cluster algorithm will hopefully be a valuable tool in testing neuroprotective agents.

Characterisation of brain edema following "controlled cortical impact injury" in rats.

Significance, origin and nature of posttraumatic brain edema are still being debated. Recently, a "controlled cortical impact injury" (CCII) was introduced to model traumatic brain injury. Purpose of this study was to investigate the development and nature of brain edema following CCII. Traumatic brain injury was applied to the intact dura of the left hemisphere in Sprague-Dawley rats (n = 52, 250-350 g b.w.). Ketamine/xylazine-anesthesia or inhalation-anesthesia were used. A pneumatic impactor with a diameter of 5 mm contused the temporo-parietal cortex with a velocity of 7 m/s and an impact depth of 2 mm. 24 hours post injury the brains were removed. Posttraumatic hemispheric swelling and water content were determined gravimetrically, Evans blue extravasation spectrophotometrically, area and volume of ischemia by staining with TTC. MRI studies were performed with T1-,T2- and diffusion-weighted sequences. Posttraumatic swelling following CCII was 14.3 +/- 3.1%. Brain water content increased to 82.5 +/- 0.5% in lesioned hemisphere compared to 79.9 +/- 0.2% in control hemisphere. Following TTC staining, the average ischemic tissue volume was 56.7 +/- 19.2 mm3. There was a moderate uptake of Evans blue into the lesioned hemisphere. MRI studies demonstrated edema in 35.4 +/- 9.5 mm3 of the lesioned hemisphere. Gd-DTPA was taken up early after trauma only. A significantly decreased ADC (apparent diffusion coefficient) indicates the cytotoxic (ischemic) component of edema in this model. In conclusion, CCII produces significant posttraumatic brain swelling and edema which is both, of vasogenic and cytotoxic nature. Thus, the CCII models the human cortical contusion more appropriately and opens new avenues for therapeutical studies focussing on cortical contusions.

The ventricular depolarization gradient: effects of exercise, pacing rate, epinephrine, and intrinsic heart rate control on the right ventricular evoked response.

A new pacing technique is described that permits high fidelity recording of the paced ventricular evoked response, including cardiac depolarization. Integration of the paced R wave yields the ventricular depolarization gradient (GD), which is dependent on activation sequence and the spatial dispersion of activation times. GD was studied in 27 dogs to determine the effects of treadmill exercise at fixed rate pacing (n = 10), elevation of heart rate in the absence of stress (n = 20), epinephrine at fixed rate (n = 6), and exercise in the presence of normal chronotrophic response (n = 7). Low level exercise (1 mph, 2 min, 15 degrees) at a fixed heart rate produced significant (P less than 0.0005) decreases in GD that averaged -10.8 +/- 4.0% (mean +/- SD). The rate of change in GD was faster at the onset of exercise than at its cessation (P less than 0.0005). Artificial elevation of heart rate at rest produced significant (P less than 0.0005) increases in GD; mean sensitivity of GD to rate was 0.27 +/- 0.12%/beats/min. Intravenous injection of epinephrine produced significant (P less than 0.001) decreases in GD at two dosage levels (2.5 and 5.0 micrograms/kg) when evaluated at two baseline pacing rates (150 and 190 beats/min); mean changes in GD were -20.64 +/- 0.53% (2.5 micrograms/kg at 150 beats/min), -25.19 +/- 4.20% (5.0 micrograms/kg at 150 beats/min), -14.18 +/- 5.19% (2.5 micrograms/kg at 190 beats/min), and -24.22 +/- 4.94% (5.0 micrograms/kg at 190 beats/min). Sensitivity of GD to epinephrine was dose-dependent (P less than 0.01) at each baseline rate, but was independent (P greater than 0.05) of the rate itself. In the presence of a normal chronotropic response, GD remained unchanged (P greater than 0.5) during exercise in spite of significant elevation in heart rate (105.0 to 167.1 beats/min, P less than 0.001). These data suggest the presence of an intrinsic negative-feedback control mechanism that maintains GD constant in the healthy heart during homeostatic disturbance. Applications in closed-loop rate adaptive pacing are described.

Automatic shimming for localized spectroscopy.

Localized in vivo nuclear magnetic resonance studies often require a high spectral resolution not achievable with the basic shim of a whole-body magnetic resonance magnet. Therefore, the magnetic field homogeneity needs to be optimized in the selected volume of interest within a reasonable time. For this purpose, a method of automatic shimming was developed and tested on phantoms and volunteers. The volume selection is performed by means of a surface coil or by using a localization method which generates a stimulated echo from the volume of interest. The optimization procedure uses the time integral over the magnitude of the free induction decay or echo signal as homogeneity criterion. A complete shimming process generally requires only 80 transients. Test experiments were conducted on various volume sizes ranging from 2 X 2 X 2 cm3 to 15 X 15 X 15 cm3 inside a large phantom. The resulting linewidth in small volumes at the magnet center compared well with the natural linewidth determined by means of the Carr-Purcell-Meiboom-Gill sequence. As expected, shimming in selected volumes at off center positions led to somewhat broader lines. Results obtained on volunteers demonstrate the practical value of this rapid, automatic shimming method for in vivo studies.

Multiple chemical shift selective (CHESS) MR imaging using stimulated echoes.

Recently, stimulated echo acquisition mode (STEAM) magnetic resonance (MR) imaging has been demonstrated as a new tool for multiparametric MR imaging studies. Applications of the chemical shift selective (CHESS) STEAM technique using a 2.0-T whole-body MR imaging system are reported in which a series of contiguous cross-sectional images of the head and the pelvis were acquired. Because selective excitation of the desired component is employed rather than elimination of the unwanted component, this method yields an improved degree of spectral resolution which is dependent only on the homogeneity of the static magnetic field. For routine medical applications, no sophisticated adjustment of the CHESS pulse is needed, as reported in previous methods.

Influence of radiofrequency amplifier nonlinearities on nuclear magnetic resonance image quality.

The quality of nuclear magnetic resonance (NMR) image is degraded by a number of disturbing influences. In this article the influence of a nonlinear radiofrequency receiving amplifier is investigated. The effect of a cubic nonlinearity on the NMR signal is analyzed. Finally, the influence on the NMR image is studied for Fourier reconstruction techniques. As a result, the images are degraded by an additional term which is proportional to a parameter characterizing the nonlinearity. The additional term causes homogeneous objects to appear inhomogeneous and gives rise to image intensity outside the object. Under normal conditions the image degradation is negligible.

Lateral inverse filtering of ultrasonic B-scan images.

The formation of ultrasonic B-scan images using parallel beams may be modelled as a lateral, one-dimensional convolution of the beam profile and an unknown but wanted reflection coefficient. Lateral inverse filtering, or deconvolution, might therefore be used to improve the image quality. Two different deconvolution techniques are applied to both an image of a tissue mimicking phantom and a human liver. An enhancement of the resolution (defined as the reciprocal of the half-width of the image of a point reflector) of about 1.4 is achieved. This is in good agreement with the previously derived formula R = square root 1n SNR, which relates the signal-to-noise ratio, SNR, to the resolution enhancement, R. However, each method also creates artifacts, and despite the slight resolution enhancement, the deconvoluted liver images do not exhibit more information nor are they more appealing. So it is felt that the computational effort is wasted. This failure is not a fault of the special deconvolution techniques tried here, but rather caused by the logarithmic dependence of R on SNR and by the noise level, which is largely due to macro- and microscopic inhomogeneities of the tissue and cannot be made arbitrarily small.