Human-sized magnetic particle imaging for brain applications.

Determining the brain perfusion is an important task for diagnosis of vascular diseases such as occlusions and intracerebral haemorrhage. Even after successful diagnosis, there is a high risk of restenosis or rebleeding such that patients need intense attention in the days after treatment. Within this work, we present a diagnostic tomographic imager that allows access to brain perfusion quantitatively in short intervals. The device is based on the magnetic particle imaging technology and is designed for human scale. It is highly sensitive and allows the detection of an iron concentration of 263 pmolFe ml-1, which is one of the lowest iron concentrations imaged by MPI so far. The imager is self-shielded and can be used in unshielded environments such as intensive care units. In combination with the low technical requirements this opens up a variety of medical applications and would allow monitoring of stroke on intensive care units.

Geometry planning and image registration in magnetic particle imaging using bimodal fiducial markers.

PURPOSE: Magnetic particle imaging (MPI) is a quantitative imaging modality that allows the distribution of superparamagnetic nanoparticles to be visualized. Compared to other imaging techniques like x-ray radiography, computed tomography (CT), and magnetic resonance imaging (MRI), MPI only provides a signal from the administered tracer, but no additional morphological information, which complicates geometry planning and the interpretation of MP images. The purpose of the authors' study was to develop bimodal fiducial markers that can be visualized by MPI and MRI in order to create MP-MR fusion images. METHODS: A certain arrangement of three bimodal fiducial markers was developed and used in a combined MRI/MPI phantom and also during in vivo experiments in order to investigate its suitability for geometry planning and image fusion. An algorithm for automated marker extraction in both MR and MP images and rigid registration was established. RESULTS: The developed bimodal fiducial markers can be visualized by MRI and MPI and allow for geometry planning as well as automated registration and fusion of MR-MP images. CONCLUSIONS: To date, exact positioning of the object to be imaged within the field of view (FOV) and the assignment of reconstructed MPI signals to corresponding morphological regions has been difficult. The developed bimodal fiducial markers and the automated image registration algorithm help to overcome these difficulties.

Effects of vigabatrin on brain GABA+/Cr signals in focus-distant and focus-near brain regions monitored by 1H-NMR spectroscopy.

The new antiepileptic drug vigabatrin (VGB) increases gamma-aminobutyric acid (GABA) in the brain. We compared GABA+/Cr signals measured focus-near and focus-distant and correlated it with the degree of response to VGB. Brain GABA+/Cr signals were measured in 17 epileptic patients in structurally normal appearing tissue by nuclear proton magnetic resonance (1H-NMR) spectroscopy using a special editing sequence for GABA. In 11 patients the measurements were done in brain areas distant to focus and in six near to focus. Full-responders (seizure reduction of >or=50% at the end of the treatment phase) and partial-responders (seizure reduction of >or=50% at the end of the first month of treatment but

Influence of pyridoxal 5'-phosphate alone and in combination with vigabatrin on brain GABA measured by 1H-NMR-spectroscopy.

Both iso-forms of the gamma-aminobutyric acid (GABA) synthesising enzyme and also the GABA degrading enzyme need pyridoxal 5'-phosphate (PP) as co-enzyme. The aim of the study was to investigate the influence of PP alone and in combination with various doses of vigabatrin (VGB) on brain GABA levels. In eight healthy subjects 300 mg/d PP and various doses of VGB (range, 1000 mg/d to 4000 mg/d) were given alone or in combination. The GABA+/creatine (Cr) signals in both occipital lobes were measured before treatment, during monotherapy with PP or VGB, and during combination of both using 1H-NMR-spectroscopy (1H-NMRS). PP alone did not change the GABA+/Cr signals. VGB alone increased the GABA+/Cr signals in both hemispheres. The combination PP and low-medium dosed VGB (1000-2000 mg/d) did not increase the GABA+/Cr signals. The effects of the combination of PP and high dosed (3000-4000 mg/d) VGB on the GABA+/Cr signals varied depending on the sequence of the drugs and dose of VGB. PP alone has no effect on the GABA+/Cr signals in healthy volunteers. The combination of PP and low-high dosed VGB had inconsistent effects on the GABA+/Cr signals compared to a VGB monotherapy because PP activates also the GABA-degrading enzyme GABA-transaminase.

Evaluation of the anatomical and functional properties of deglutition with various kinetic high-speed MRI sequences.

We evaluated various fast MR sequences for obtaining anatomical and dynamic functional information during deglutition. Seven healthy volunteers underwent MRI of the oropharynx during swallowing of an oral positive-contrast agent. Single-slice imaging was performed in the median sagittal plane while subjects were in a supine position. Twenty serial images were obtained using EPI, FLASH, and turbo-FLASH sequences. The dynamic (movement-related) information and the anatomical resolution of the soft tissues were evaluated during deglutition. The FLASH sequence provided high-quality images at rest. During swallowing, however, the images were significantly degraded by movement artifacts and had inferior temporal resolution. The EPI evidenced better temporal resolution, but was degraded by strong distortions and movement artifacts. The turbo-FLASH sequence provided the best temporal resolution and sufficient spatial resolution during motion. This sequence proved optimal for the investigation of swallowing function, and is expected to be of value for the documentation of functional disturbances in patients with oropharyngeal pathology.

Effects of vigabatrin on brain GABA+/CR signals in patients with epilepsy monitored by 1H-NMR-spectroscopy: responder characteristics.

PURPOSE: Vigabatrin (VGB) is a new antiepileptic drug that increases the human brain gamma-aminobutyric acid (GABA) level by irreversibly inhibiting GABA transaminase. Although some patients respond to VGB with a significant seizure reduction, others do not. The aim of this study was to identify possible responders before or in an early phase of VGB treatment by measuring the GABA and homocarnosine contaminated with macromolecules/creatine and phosphocreatine ratio (GABA+/Cr) signal by means of proton-nuclear magnetic resonance (1H NMR) spectroscopy. METHODS: Measurements were performed immediately before and after a titration period of 1 month (2 g/day during the past 2 weeks). A third measurement followed a maintenance period of 3 months (2 or 3 g/day). In 14 patients with drug-resistant temporal lobe epilepsy and 3 patients with occipital lobe epilepsy, GABA+/Cr was measured in the ipsilateral (i.e., epileptogenic) hemisphere and contralateral (i.e., nonepileptogenic) hemisphere in a volume of 8 cm3. RESULTS: Depending on the therapeutic efficacy of VGB, we defined three groups: (a) full responders (n = 7), (b) nonresponders (n = 7), and (c) partial responders (n = 3). The nonresponders had no significant change in the GABA+/Cr signal during the treatment compared with baseline. The full responders had a significant increase of the GABA+/Cr signal during the whole treatment phase and a lower ipsilateral level at baseline. The partial responders had also a lowered ipsilateral GABA+/Cr signal at baseline and an increase during treatment but a decrease when the seizures started again. CONCLUSIONS: Responders to VGB could be identified by a lower ipsilateral baseline GABA+/Cr signal and a steeper increase during VGB treatment. However, it was not possible to predict the duration of the response (full versus partial responder) with these criteria.

Coronary magnetic resonance angiography for the detection of coronary stenoses.

BACKGROUND: An accurate, noninvasive technique for the diagnosis of coronary disease would be an important advance. We investigated the accuracy of coronary magnetic resonance angiography among patients with suspected coronary disease in a prospective, multicenter study. METHODS: Coronary magnetic resonance angiography was performed during free breathing in 109 patients before elective x-ray coronary angiography, and the results of the two diagnostic procedures were compared. RESULTS: A total of 636 of 759 proximal and middle segments of coronary arteries (84 percent) were interpretable on magnetic resonance angiography. In these segments, 78 (83 percent) of 94 clinically significant lesions (those with a > or = 50 percent reduction in diameter on x-ray angiography) were also detected by magnetic resonance angiography. Overall, coronary magnetic resonance angiography had an accuracy of 72 percent (95 percent confidence interval, 63 to 81 percent) in diagnosing coronary artery disease. The sensitivity, specificity, and accuracy for patients with disease of the left main coronary artery or three-vessel disease were 100 percent (95 percent confidence interval, 97 to 100 percent), 85 percent (95 percent confidence interval, 78 to 92 percent), and 87 percent (95 percent confidence interval, 81 to 93 percent), respectively. The negative predictive values for any coronary artery disease and for left main artery or three-vessel disease were 81 percent (95 percent confidence interval, 73 to 89 percent) and 100 percent (95 percent confidence interval, 97 to 100 percent), respectively. CONCLUSIONS: Among patients referred for their first x-ray coronary angiogram, three-dimensional coronary magnetic resonance angiography allows for the accurate detection of coronary artery disease of the proximal and middle segments. This noninvasive approach reliably identifies (or rules out) left main coronary artery or three-vessel disease.

Real-time interactive magnetic resonance imaging with multiple coils for the assessment of left ventricular function.

Interactive real-time examination of left ventricular function in healthy volunteers both under rest and stress conditions has been performed. For this purpose, a system combining an interactive user interface, an ultrafast segmented echo-planar imaging sequence, and real-time reconstruction and display of the acquired images was designed. Magnetic resonance images were acquired at rates of up to 20 images per second with multiple receiver coils. By using a sliding window reconstruction technique, reconstruction rates of up to 60 images per second were achieved with a latency of < 100 msec. The quality of the real-time images was evaluated both qualitatively and quantitatively and was found to be appropriate for the determination of left ventricular function. It is concluded that the combination of dedicated components provides a convenient modality for the high-quality visualization of left ventricular function under rest and stress conditions at video frame rates with magnetic resonance imaging. J. Magn. Reson. Imaging 1999;10:826-832.

Detection of glutathione in the human brain in vivo by means of double quantum coherence filtering.

The feasibility of selective in vivo detection of glutathione (L-gamma-glutamyl-L-cysteinyl-glycine, GSH) in the human brain by means of (1)H magnetic resonance spectroscopy (MRS) at 1.5 T is demonstrated. A double quantum coherence (DQC) filtering sequence was used in combination with PRESS volume selection. The strongly coupled cysteinyl CH(2) compound of GSH was found to be the most suitable target for spectral editing. Analytical calculations employing a product operator description of the cysteinyl ABX three-spin system were made in order to optimize the inherent yield of the sequence. A pulse phase calibration procedure, which precedes the spectrum acquisition, secures maximal signal yield independently of the spatial localization of the volume of interest and thus comparability between individual examinations. In vitro tests show that the DQC filtering method provides good discrimination between the GSH signal at 2.9 ppm and the interfering resonances of creatine, gamma-aminobutyric acid (GABA) and aspartate. In measurements in the frontal lobe of 12 healthy volunteers a mean ratio of GSH signal to tissue water signal of 5.7 +/- 2.3 x 10(-5) was found, corresponding to a mean GSH tissue concentration of 2-5 mmol/L. The proposed technique allows for the detection of a biologically highly relevant metabolite at moderate field strength. Magn Reson Med 42:283-289, 1999.

Effects of vigabatrin intake on brain GABA activity as monitored by spectrally edited magnetic resonance spectroscopy and positron emission tomography.

A deficit in gamma-aminobutyric acid (GABA) levels in the brain or the cerebrospinal fluid (CSF) is found in many epilepsy patients. Frequency and severity of seizures may be reduced by treatment with GABA increasing medicaments as e.g. vigabatrin, an irreversible inhibitor of GABA-transaminase. For a better understanding of the associated effects, healthy volunteers were examined with magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) before and after intake of different doses of vigabatrin. For the MRS examinations, a dedicated localized spectral editing method was developed to determine GABA levels. The 11C-flumazenil (FMZ)-PET protocol allowed determination of GABA-A receptor binding. The results show a clear and dose-dependent increase in the brain GABA levels after the medication period as compared to the baseline values. The GABA-A receptor binding, on the other hand, did not change significantly.

Quantitative 1H MRS in the evaluation of mesial temporal lobe epilepsy in vivo.

Hippocampal metabolite concentrations were determined by localized in vivo proton magnetic resonance spectroscopy (1H MRS) in eleven patients suffering from refractory mesial temporal lobe epilepsy (MTLE), as well as in eleven age-matched healthy volunteers, and compared with patient history, postoperative outcome and histopathology. Main results are: 1) In patients, the decrease in N-acetylaspartate (NAA) concentrations was highly significant ipsilateral, and less but still significant contralateral to the electroencephalogram-defined focus, as compared to controls. 2) The decrease in ipsilateral NAA measured preoperatively correlates with the degree of hippocampal sclerosis but 3) does not reliably predict postoperative outcome, although there is a trend toward better outcome in patients with a marked decrease of NAA. 4) Hippocampal NAA decrease (ipsi- and contralateral) is highly correlated with early onset age of epileptic seizures. 5) Among patients with similar onset age in early childhood, there is a strong association between duration of the disease and contralateral (and, though less clear-cut, ipsilateral) NAA loss. These results are concordant with the notion of a generally progressive worsening and complicating course of symptoms in poorly controlled MTLE.

Heuristic optimization algorithms applied to the quantification of spectroscopic data.

The quantification of in vivo MR spectra imposes severe problems because of low spectral resolution and poor signal-to-noise ratio. Maximum likelihood methods are often applied. However, with conventional spectrum analysis procedures, the search for a global minimum in a multidimensional space often terminates in only a local minimum. Heuristic optimization procedures are able to circumvent this difficulty. Two approaches, the genetic algorithm and the simulated annealing, have been adapted to the quantification of MR spectra. For evaluation purposes, the procedures have been applied to synthetic and in vivo spectra with different noise levels. They both allowed a reliable spectrum quantification. The areas of most peaks were quantified reproducibly, although in some cases, the discrimination between spectroscopically almost identical metabolites (e.g., glutamate and glutamine) was not completely satisfactory. The two algorithms are found to be valuable alternative methods in the quantification of in vivo MR spectra.

Quantitative 1H MRS of the human brain in vivo based on the stimulation phantom calibration strategy.

Normal metabolite concentrations were determined in five different brain regions of healthy adult volunteers using proton magnetic resonance spectroscopy (1H MRS) in vivo. The absolute in vivo concentrations of N-acetylaspartate (NAA), creatine and phosphocreatine (Cre), and choline containing compounds (Cho) were quantified from measurements obtained with a head-shaped simulation phantom. Scanner performance and calibration accuracy were assessed by phantom experiments. Localized spectra were acquired on clinical 1.5 T systems using the PRESS localization sequence with frequency selective water suppression. Comparison of the results obtained from phantom experiments and human brain in vivo strongly suggests that reproducibility in vivo mainly depends on the topologic metabolite heterogeneity of brain tissue in combination with relative volume dislocalization.

Detection of hidden metabolites by localized proton magnetic resonance spectroscopy in vivo.

Magnetic resonance spectroscopy (MRS) allows the assessment of chemical substances in living tissue and the detection of biochemical changes associated with certain diseases. In vivo MRS, however, is usually limited in sensitivity and spectral resolution. Many resonance lines originating from metabolites of interest are overlapped by signals of other metabolites and are therefore not visible in conventional MR spectra. In order to overcome this limitation, three localized methods, a technique making use of a spectral difference, a multiple quantum filter technique, and a two-dimensional J-resolved technique, were evaluated theoretically and experimentally for the detection of gamma-aminobutyric acid (GABA) both in vitro and in vivo. All three methods are able to produce the desired results at high metabolite concentrations in vitro. For in vivo measurements the spectral difference method proofed to be most appropriate due to its relatively high sensitivity and its short acquisition time.