Overview-the role of NMR spectroscopy in epilepsy

Nuclear magnetic resonance (NMR) spectroscopy permits noninvasive, serial measurements of several metabolites with important neurobiologic roles in localized brain regions in vivo. Over the last decade, this technique has been applied to investigations of both animals and humans with epilepsy. Several nuclei that include specific proton, phosphorus, and carbon isotopes provide NMR signals that measure specific compounds in vivo. This paper reviews the studies that have used these multinuclear NMR techniques to investigate the role of these methods in the diagnosis and pathogenesis of epilepsy.     

Effects of the operating magnetic field on potential NMR contrast agents

Paramagnetic metal ions have shown promise as contrast agents for nuclear magnetic resonance (NMR) imaging. Their ability depends upon modification of the relaxation times (T1 and T2) through dipolar interactions. These interactions cause the effectiveness of the agents to be sensitive to the operating magnetic field. Studies are presented of the operating field dependence (frequency dispersion) of two metal-chelate complexes, Gd+3-ethylenediaminetetraacetate (EDTA) and Mn+2-EDTA, in a physiologically balanced electrolyte solution. Inversion recovery experiments were performed on two concentrations of each metal-chelate complex at five resonant frequencies. The frequency dispersion curves were similar in appearance for those of the corresponding aqueous solutions. The Mn+2 complex showed no unusual concentration effects. The Gd+3 complex showed an unexpected concentration dependence in the dispersion behavior. This is attributed to a difference in the dipolar correlation time between the two solutions. With its unique correlation time in electrolyte solutions, predictions of relaxation rate changes in studies in vivo may be easier for the Mn+2-EDTA complex.     

Preliminary observations on magnetic resonance imaging in refractory epilepsy

We are studying the use of magnetic resonance (MR) imaging in localization of epileptogenic foci in patients with medically refractory partial epilepsy. Imaging is performed using a prototype resistive unit operating at 0.15 T. All studies include 7 mm axial sections obtained with a partial saturation sequence (TR = 200 msec) in which signals are recovered with a spin echo (TE = 11 msec) and images reconstructed using a modified 2D Fourier transform technique. Since the temporal lobe and limbic system are the commonest site of seizure foci in this group of patients, examinations were performed with the plane of section parallel to the temporal horns of the lateral ventricles.

Consensus interpretations by a radiologist, neurologist and neurosurgeon have recognized findings considered possibly abnormal in six of 11 epilepsy patients and none of six normal volunteers.

These preliminary results indicate that further study is warranted in this group of patients. Critical evaluation of such findings must be carried out in a larger group including normals and patients with a variety of neurologic disorders.     

F 2-FDG NMR imaging of the brain in rat

Images of the rat head reflecting glucose utilization were obtained using 2-fluoro-2-deoxy-D-glucose (2-FDG) and ¹⁹F nuclear magnetic resonance (NMR) imaging. Spatial heterogeneity of glucose utilization in the rat head was clearly demonstrated showing significantly higher glucose utilization in the brain as compared to the surrounding tissues. Although the potential adverse effects of the high doses of 2-FDG (400 mg/kg) needed to perform the study preclude immediate application of this technique to clinical quantitative glucose utilization studies, the present study shows potential for future development of glucose utilization imaging by NMR.     

NMR studies of brain C-glucose uptake and metabolism: Present status

One of the common features of epilepsy is a change in glucose metabolism at the site of seizure activity during and between seizures. The noninvasive in situ study of glucose transport and metabolism by NMR can potentially provide detailed information about this phenomena. In this short review, we will discuss the principles of ¹³C-glucose NMR studies of the brain and compare the advantages and disadvantages of this method to those of ¹⁸F-deoxyglucose studies using positron emission tomography (PET).     

Time resolved spectroscopic NMR imaging using hyperpolarized Xe

We have visualized the melting and dissolution processes of xenon (Xe) ice into different solvents using the methods of nuclear magnetic resonance (NMR) spectroscopy, imaging, and time resolved spectroscopic imaging by means of hyperpolarized ¹²⁹Xe. Starting from the initial condition of a hyperpolarized solid Xe layer frozen on top of an ethanol (ethanol/water) ice block we measured the Xe phase transitions as a function of time and temperature. In the pure ethanol sample, pieces of Xe ice first fall through the viscous ethanol to the bottom of the sample tube and then form a thin layer of liquid Xe/ethanol. The xenon atoms are trapped in this liquid layer up to room temperature and keep their magnetization over a time period of 11 min. In the ethanol/water mixture (80 vol%/20%), most of the polarized Xe liquid first stays on top of the ethanol/water ice block and then starts to penetrate into the pores and cracks of the ethanol/water ice block. In the final stage, nearly all the Xe polarization is in the gas phase above the liquid and trapped inside the pores. NMR spectra of homogeneous samples of pure ethanol containing thermally polarized Xe and the spectroscopic images of the melting process show that very high concentrations of hyperpolarized Xe (about half of the density of liquid Xe) can be stored or delivered in pure ethanol.     

Optical and transport studies in coupled InAs quantum dots embedded in GaAs

We studied optical and electron transport properties of coupled InAs quantum dots (QDs) embedded in GaAs. Photoluminescence (PL) from the high dot density samples indicated asymmetry in the PL spectra when the ambient temperature is lower than about 50 K. Comparing this result with theoretical calculations, it is shown that this phenomenon is explained by the inter-dot electronic coupling effect. In the photo-conductance measurement, resonance peaks in the current–voltage characteristics were observed in the low-temperature region. The dependence of the resonance voltage on the magnetic field intensity was studied to extract the g-factor. It is also shown that the resonances are attributed to the current corresponding to the electron transport through QDs. According to these results, it is concluded that the inter-dot electronic coupling in the self-assembled InAs/GaAs QD systems occurs when the inter-dot spacing is as low as several nanometers and the ambient temperature is less than about 50 K.     

In vivo NMR T2 relaxation of experimental brain tumors in the cat: a multiparameter tissue characterization.

Experimental gliomas (F98) were inoculated in cat brain for the systematic study of their in vivo T₂ relaxation time behavior. With a CPMG multi-echo imaging sequence, a train of 16 echoes was evaluated to obtain the transverse relaxation time and the magnetization M(0) at time T = 0. The magnetization decay curves were analyzed for biexponentiality. All tissues showed monoexponential T₂, only that of the ventricular fluid and part of the vital tumor tissue were biexponential. Based on these NMR relaxation parameters the tissues were characterized, their correct assignment being assured by comparison with histological slices. T₂ of normal grey and white matter was 74 ± 6 and 72 ± 6 msec, respectively. These two tissue types were distinguished through M(0) which for white matter was only 0.88 of the intensity of grey matter in full agreement with water content, determined from tissue specimens. At the time of maximal tumor growth and edema spread a tissue differentiation was possible in NMR relaxation parameter images. Separation of the three tissue groups of normal tissue, tumor and edema was based on T₂ with T_2(normal) < T_2(tumor) < T_2(edema). Using M(0) as a second parameter the differentiation was supported, in particular between white matter and tumor or edema. Animals were studied at 1–4 wk after tumor implantation to study tumor development. The magnetization M(0) of both tumor and peritumoral edema went through a maximum between the second and third week of tumor growth. T₂ of edema was maximal at the same time with 133 ± 4 msec, while the relaxation time of tumor continued to increase during the whole growth period, reaching values of 114 ± 12 msec at the fourth week. Thus, a complete characterization of pathological tissues with NMR relaxometry must include a detailed study of the developmental changes of these tissues to assure correct experimental conditions for the goal of optimal contrast between normal and pathological regions in the NMR images.     

Gadolinium-DTPA-enhanced MRI of intraocular tumors

The value of gadolinium-enhanced MRI in 30 patients with intraocular lesions has been evaluated. Seventeen patients had a uveal melanoma, two a ciliary body melanoma, three had uveal metastases, one lymphoma, four had senile macula degenerations, and three uveal nevi. Twelve of 17 patients with melanoma were followed up by MRI after ruthenium plaque therapy on 2–4 occasions. Melanomas showed high precontrast signal intensities and only a slight enhancement after intravenous Gd-DTPA was given. After ruthenium plaque therapy precontrast signal intensities (SI) decreased while a moderate signal increase on postcontrast scans was noted. Scars or tumor residues were better delineated on enhanced images. All other tumors than melanotic melanomas showed low SI on precontrast scans and a high signal increase after Gd-DTPA administration. Small amelanotic tumors were better delineated on postcontrast scans. In addition Gd-DTPA-enhanced MRI allowed differentiation between tumor and hemorrhage. No signal increase after Gd-DTPA application was seen in subretinal or vitreous hemorrhages of varying ages.     

Local structure in perovskite relaxor ferroelectrics: high-resolution Nb 3QMAS NMR

Solid solutions of (1'-x)Pb(Mg(1/3)Nb(2/3))O3xPb(Sc(1/2)Nb(1/2))O3 (PMN/PSN) have been investigated using high-resolution 93Nb 3-quantum magic-angle spinning nuclear magnetic resonance experiments (3QMAS NMR). In previous MAS NMR investigations, the local B-cation ordering in these relaxor ferroelectric solid solutions was quantitatively determined. However, in conventional one-dimensional MAS spectra the effects of chemical shifts and quadrupole interaction are convoluted; this, in addition to the insufficient resolution, precludes reliable extraction of the values of isotropic chemical shift and quadrupole coupling product. In the current 3QMAS investigation, 93Nb spectra are presented for concentrations x=0, 0.1, 0.2, 0.6, 0.7, and 0.9 at high magnetic field (19.6 T) and fast sample spinning speed (35.7 kHz). Seven narrow peaks and two broad components are observed. The unique high-resolution of the two-dimensional 3QMAS spectra enables unambiguous and consistent assignments of spectral intensities to the specific 28 nearest B-site neighbor (nBn) configurations, (NMg, NSc, NNb) where each number ranges from 0 to 6 and their sum is 6. It is now possible to isolate the isotropic chemical shift and quadrupole coupling product and separately determine their values for most of the 28 nBn configurations. The isotropic chemical shift depends linearly on the number of Mg2+ cations in the configuration; delta iso CS=(13.7 +/- 0.1)NMg-970 +/- 0.4 ppm, regardless of the ratio NSc/NNb. For the seven Nb5+-deficient configurations (NMg, 6-NMg, 0) and the pure niobium configuration (0, 0, 6), the quadrupole coupling products (and hence the electric field gradients) are small (PQ approximately 6-12 MHz) and for the remaining configurations containing small, ferroelectric active Nb5+ ions, the quadrupole coupling products are significantly larger (PQ approximately 40 MHz), indicating larger electric field gradients.     

Magnetic resonance imaging of soft-tissue tumors: Comparison with computed tomography

Twenty-seven patients with soft-tissue tumors were examined with a Picker 0.15-tesla resistive magnet and by computed tomography (CT). In all but one patient, MRI was better than or equal to CT in defining the anatomic extent of the tumor. We could determine whether major vascular structures were engulfed by the tumor in 80% of the MRI examinations but only in 62% of the CT scans. MRI and CT were equally effective in determining the presence or absence of bony invasion. The MRI images of all the tumors showed increased signal intensity relative to normal muscle when spin-echo (SE) sulse sequences with long repeat times were used (SE: echo time [TE], 60 ms; repetition time [TR], 2,000 ms). When T1 weighted pulse sequences were used (SE: TE, 30 ms; TR, 500 ms or inversion recovery: inversion time, 500 ms; TE, 40 ms; TR, 2,000 ms) the malignant tumors showed decreased signal intensity compared to normal muscle. Only lipomas showed high signal intensity on both T1 and T2 weighted pulse sequences.     

Localized in vivo proton spectroscopy of the bone marrow in patients with leukemia

Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate the haemopoietic (iliac bone) and fatty bone marrow (tibia) in patients with leukemia and polycythaemia vera. Selective measurements of the relaxation times T₁ and T₂ for the “water” and “fat” resonances in the bone marrow spectra were performed. Nine patients with acute leukemia and three patients with chronic leukemia were examined at diagnosis. Three patients with acute leukemia in remission were also examined. Five of the leukemic patients had follow-up examinations performed in relation to chemotherapeutic treatment. Nine patients with polycythaemia vera and 21 normal control subjects were examined with identical methods for comparison. All patients had bone marrow biopsies performed prior to every MR examination. Significant differences could be detected in the spectral patterns from iliac bone marrow in patients with leukemia at diagnosis compared to the healthy normal controls. The “relative water content” was increased in the iliac bone marrow spectra of the leukemic patients compared to the normal subjects, which indicates an increase in the amount of haemopoietic tissue and a corresponding decrease in marrow fat content. The T₁ relaxation times of the “water” resonance in the spectra from the iliac bone marrow of the leukemic patients were significantly prolonged at diagnosis, compared to the normal controls and the patients with polycythaemia vera. After chemotherapeutic induction of remission, the spectra from the iliac bone marrow in the patients with leukemia resembled normal spectra. Four leukemic patients had abnormal spectra from the tibial bone marrow and one patients showed early changes in tibial marrow during chemotherapeutic treatment, before any major changes could be detected in the iliac bone marrow.     

Cine MR voiding cystourethrogram in adult normal males

Cine voiding cystourethrogram was performed in 15 normal subjects using T₁-weighted Turbo FLASH sequence. It showed the sequence of emptying of bladder, detrusor muscle contraction, opening of the sphincters, and various parts of urethra. It was found to be a good noninvasive test to study the dynamics of lower urinary tract with out disturbing the state of the physiology.     

Micromagnetic simulation of magnetization reversal in controlled mesoscopic ferromagnetic junction

Magnetisation switching process and corresponding domain structures of mesoscopic ferromagnetic junction with different thickness are studied with micromagnetic simulation using Landau–Lifshiz–Gilbert equations. It is demonstrated by simulation results that the reversal process and switching field are dominated by the wide pad parts and only weakly depend on the wire parts.     

Estimating patient dielectric losses in NMR imagers

Dielectric losses in the patient may impair radiofrequency receiver coil sensitivity, and transmitter coil efficiency, in nuclear magnetic resonance (NMR) imagers. The frequency dependence of this loss mechanism is derived. Patient losses in a solenoidal head coil used for imaging heads were simulated by a cylindrical saline phantom. The frequency dependence of the loss introduced by the phantom can indicate whether dielectric losses in the patient will be significant compared to eddy current losses. The detuning caused by the phantom is used to calculate an upper limit for the distributed stray capacitance between coil and patient. Given the approximate conductivity of the patient, an upper limit for the dielectric loss can be estimated. Some methods of reducing patient dielectric losses are suggested.     

Myocardial proton spin-lattice relaxation times in vitro: Effect of elapsed time after excision

An assumption made in using excised tissue for in vitro nuclear magnetic resonance (NMR) studies is that variables of interest, such as spin-lattice (T₁) relaxation times, remain stable for periods of time after excision sufficient to perform NMR spectroscopy. In this study, we evaluated the changes in T₁ of rat myocardium, measured at two NMR field strengths, at serial time intervals up to 72 hours postmortem. Left ventricular myocardium from six male Sprague-Dawley rats was excised and stored at room temperature in sealed NMR sample tubes. Spin-lattice relaxation times were determined with a modified inversion-recovery pulse sequence immediately postmortem and at intervals up to 72 hours post-excision; NMR studies were performed using 90 MHz and 360 MHz spectrometers. A gradual decrease in T₁ was noted with increasing time post-excision; T₁ was not significantly shorter than baseline until 72 hours postmortem at either field strength. The rate of change of T₁ was similar at the two field strengths. At any given time post-excision, T₁ was significantly higher (p < 0.001) at 360 MHz than at 90 MHz. We conclude that, with proper tissue handling and storage techniques, rat myocardial T₁ is stable postmortem sufficiently long to permit meaningful NMR studies of excised tissue.     

MR of an adrenal pseudocyst

We describe the appearance of an adrenal pseudocyst on MRI and CT. The MR characteristics of the lesion were noteworthy in that the lesion had two components with different imaging characteristics. The larger component was of low signal intensity on both T₁- and T₂-weighted images and might have been confused with an adrenal adenoma.     

Cardiac lipoma: Six-year follow-up with MRI characteristics, and a review of the literature

A total of 63 cardiac lipomas have been reported to date. Although most of these rare tumors cause no symptoms, a few can have a detrimental effect on myocardial function as well as displacing and encasing the coronary arteries. This case of a cardiac lipoma was initially seen in 1982. The lipoma was found to be nonresectable at surgery due to involvement of the coronary arteries. This neoplasm was characterized with magnetic resonance imaging in 1989 on a follow-up visit. Magnetic resonance imaging is shown to be superior to computed tomography for identifying the relationship of the lipoma to the coronary arteries. This is a significant factor in determining resectability.     

A rotating phantom for the study of flow effects in MR imaging

A common type of phantom used for the study of flow effects in MR imaging is the tube phantom, where a liquid passes through a set of tubes placed in the main magnetic field of an MR scanner. Among the disadvantages with this type of phantom are that a distribution of velocities is present in each tube, and that quantifications of flow effects using tube phantoms may be very time-consuming. In this work, we describe the design and the properties of a rotating wheel flow phantom used for quantification of the effects of flow through the imaging plane as well as in the imaging plane. The proposed phantom is constructed as a rotating gel-filled wheel, surrounded by static volumes filled with the same gel, and the evaluation of the information from rotating and static parts is made with a specially designed computer program. The phantom can be used as a plug flow phantom covering simultaneously an interchangeable velocity interval, which at present has the range −52 mm/s, +52 mm/s. It is shown that the phantom gives adequate information on the dependence of pixel content on first-order motion in MR modulus and phase images. Among the fields of application are rapid calibration of MR imaging units for flow determination using phase information, as well as testing of pulse sequence characteristics and verification of theoretical predictions concerning the flow dependence in MR images.     

An assessment of the safety of rapidly changing magnetic fields in the rabbit: Implications for NMR imaging

The effects of rapidly changing magnetic fields on the cardiac and respiratory functions of anaesthetised rabbits have been investigated. No changes were observed using pulsed fields with peak rates of change of 60 T/sec. The implications of these experiments for the safety of NMR imaging are discussed.