Quantitative MR in the diagnosis of multiple sclerosis.

In patients with multiple sclerosis (MS), the apparently uninvolved cerebral white matter between demyelinated plaques may have biochemical abnormalities. To what degree the changes in the white matter contribute to symptomatology in MS is unknown. In 39 patients with multiple sclerosis, and in 39 age-matched nondiseased volunteers, T1 and T2 were calculated from spin-echo images in four regions of apparently uninvolved white matter. In three of four white matter areas, the average T1 and T2 were significantly longer in the patients than in the controls. The T1 correlated with the disability, measured by the Kurtzke Extended Disability Status Scale, although the correlation was marginally significant. The results suggest that in patients with MS, white matter disease that is not visualized in MR as distinct foci of abnormal signal intensity may contribute to disease burden and disability.

T1 and T2 in the cerebrum: correlation with age, gender, and demographic factors.

The authors measured the T1 and T2 of cerebral tissue in 164 volunteers aged 5-90 years and correlated T1 and T2 with age, gender, and various demographic variables. A weak correlation with statistical significance was found between age and T1 and T2 in white and gray matter structures. The T1 and T2 in the telencephalon increased by about 0.1% per year. No correlation of T1 or T2 with any other demographic, life-style, or medical factors was found.

Contrast enhancement in spinal MR imaging.

We evaluated 44 patients with suspected spinal tumors or previous laminectomies with gadolinium-DTPA MR imaging in order to characterize the enhancement in normal, postoperative, and neoplastic intraspinal tissue. Using the signal intensity of CSF as an internal control, we calculated the percentage increase in signal intensity from pre- to postgadolinium studies. Tumors (astrocytoma, ependymoma, schwannoma) enhanced 70-350%; epidural scar, normal epidural venous plexus, and dorsal root ganglion enhanced up to 200%. Contrast enhancement does not per se distinguish neoplastic from normal tissue. Enhancement with gadolinium-DTPA appeared to increase the conspicuousness of intramedullary tumors but not intraosseous metastases. We believe that gadolinium-enhanced MR imaging is a valuable adjunct to routine MR imaging in the evaluation of intraspinal neoplastic processes and may be useful in delineating normal and postoperative structures in the spinal canal.

T1 and T2 measurements on a 1.5-T commercial MR imager.

In order for relaxation times to be used in clinical diagnosis, the precision of the measurement must be determined. The authors measured T1, T2, and proton density in a phantom and in human volunteers to determine the reproducibility of the method. The coefficient of variance of T1 measurements in the phantom during a 15-month period with two software upgrades was 5%. Variance of T2 measurements with any given software was 4% or less, and overall in the 15-month period, with two software changes, the T2 reproducibility was between 6% and 9%. The reproducibility is sufficiently high that precise clinical measurements of T1, T2, and proton density are feasible.

Truncation artifact in MR images of the intervertebral disk.

A cadaver's vertebral column, a phantom, and a volunteer were imaged on a 1.5-T MR scanner to study the thin, uniform, dark, transverse lines that characterize some intervertebral disks. An artifactual dark line appears when the field of view (FOV) and matrix steps (n) are chosen so that d = FOV/n, where d equals the intervertebral disk height, or spacing between phantom vertebrae. The artifact is caused by the truncation effect. An artifactual dark line is differentiated from a dark line caused by anatomic variables, and means for reducing such lines by modifying imaging parameters are discussed.

Sensitivity of Gd-DTPA-enhanced MR imaging of benign extraaxial tumors.

The effect of gadolinium diethylenetriaminepentaacetic acid (DTPA) on the sensitivity of cranial magnetic resonance (MR) imaging was measured in a prospective blinded study. Twenty-two consecutive patients with benign extraaxial tumors underwent MR imaging on a 1.5-T system without and with intravenous administration of Gd-DTPA. Readers independently interpreted the unenhanced and enhanced images without clinical information. The interpretations were compared with the anatomically verified diagnoses. Gd-DTPA improved the sensitivity of MR imaging for benign extraaxial tumors, especially in cases of residual or recurrent acoustic neuromas, multiple tumors (e.g., neurofibromatosis), or inconclusive unenhanced MR images. Enhancement with Gd-DTPA impaired the identification of a skull base tumor.

"Truncation" artifact in MR images of the internal auditory canal.

Dry skulls and a phantom were studied to determine whether an intracanalicular dark band in MR images of some acoustic neuromas could be artifactual. A "truncation" artifact was detected in the internal auditory canals of the dry skulls and in a simulated internal auditory canal of the phantom when the width of the canal approximately equaled 4 X (field of view) /N, where N equals 128 or 256, depending on the number of gradient steps chosen. The "truncation" artifact should not be confused with CSF between normal nerves when a canal contains tumor.

Benign extraaxial tumors: contrast enhancement with Gd-DTPA.

Meningiomas, acoustic neuromas, and other benign extraaxial tumors have little contrast with adjacent brain tissue on conventional magnetic resonance (MR) images. The contrast enhancement produced by intravenous administration of 0.1 mmol/kg of gadolinium-DTPA in these tumors was measured on T1 MR images. Acoustic neuromas showed the greatest enhancement (average, 310%), meningiomas the next greatest (average, 180%), and neurofibromas, glomus tumors, and pituitary microadenomas the least enhancement. The degree of enhancement was almost always greater at 3 minutes than at 25 or 55 minutes. Contrast between the tumor and adjacent tissue resulted from tumor enhancement in neuromas, meningiomas, and neurofibromas and from enhancement of the surrounding tissue in pituitary microadenomas.

Methodology for the measurement and analysis of relaxation times in proton imaging.

Measurements of proton T1 and T2 were performed on GdCl3 solutions (20 less than T2 less than 500 msec, 90 less than T1 less than 1000 msec) on large-bore NMR imaging systems operating at 1.0T and 1.5T. CPMG multi-echo (ME), multiple saturation recovery (MSR) and modified fast inversion recovery (MFIR) pulse sequences as well as a sequence that combines and interleaves T1 and T2 weighted data acquisition (which we call "multiple saturation-recovery multiple-echo" (MSRME) were used. The relaxation data are compared to those obtained on a small bore NMR spectrometer operated at 1.5T. T1 and T2 values for the solutions were found to be the same within 10% for the two fields. Reproducibility of measurements of T1, T2 and the unnormalized spin density of the solutions was better than 5%. Systematic errors, amenable to correction through calibration, are noted in the imager T1 and T2 values. T1 and T2 values for some typical neural tissues at 1.5T and body tissue at 1.0T for human volunteers were obtained and are tabulated.

Reproducibility of relaxation and spin-density parameters in phantoms and the human brain measured by MR imaging at 1.5 T.

The reproducibility of T1, T2, and proton density, measured in phantoms and the human brain was evaluated by proton imaging techniques. The sequence used to derive T1 and density values was a multiple-saturation recovery which consists of four pairs of 90 degrees pulses, followed by a 180 degrees phase reversal pulse, generating four T1-weighted images. T2 was derived from a multiple-echo sequence, generating four T2-weighted images. The data were analyzed by fitting the pixel intensities to the respective equations by means of nonlinear multiparameter least-squares analysis. Short-term reproducibility between four consecutive scans was evaluated to be 1-4% depending on location with a phantom covering the entire span of physiologic T1 and T2 values. A second phantom containing a series of identical samples served to study the dependence of the apparent T1 and T2 on position, both radially and axially, with respect to magnet isocenter. Reproducibility across the field of view was found to be better than 7% (T1 and T2). This phantom was further used to evaluate effects of long-term reproducibility, which at each location varied from 5-14% (T1) and 2-10% (T2). Finally, interinstrument reproducibility, tested by means of the same protocol on three different instruments, all operating at the same magnetic field and using largely identical hardware for each location, was found to be 1-14% (T1) and 2-10% (T2). The positional dependence of the apparent relaxation times appears to be systematic and may be due to variations in the effective field, caused by magnet and rf inhomogeneity. Finally, brain tissue relaxation and spin-density data were determined using the same protocol in 37 scans performed on 27 normal volunteers. The tissues analyzed were putamen, thalamus, caudate nucleus, centrum semiovale, internal capsule, and corpus callosum. Excellent accordance was further obtained between left and right hemispheres.

Cranial tissues: normal MR appearance after intravenous injection of Gd-DTPA.

The effect of intravenously administered gadolinium DTPA on signal intensity of normal intracranial structures was analyzed in 25 patients. Magnetic resonance (MR) image enhancement with Gd-DTPA differs from image enhancement on computed tomography with aqueous iodinated contrast media. Marked contrast enhancement owing to Gd-DTPA was observed in the pituitary gland, infundibulum, cavernous sinus, cranial nerves, choroid plexus, and nasal mucosa. Enhancement was not visible routinely in the falx cerebri, tentorium cerebelli, dura, or rapidly flowing blood. The efficacy of Gd-DTPA in any individual MR study may be assessed by observing the signal intensity of the pituitary gland, pituitary stalk, or nasal mucosa.

Quantification of contrast in clinical MR brain imaging at high magnetic field.

The relative contrast between two tissues in a magnetic resonance (MR) image is shown to be quantifiable for any combination of pulse timing parameters, provided the intrinsic parameters are known. Based on multiple inversion-recovery and spin echo images, a region-of-interest T1, T2 and density analysis was conducted at 1.4T in selected patients with diagnosed neuropathology for various brain tissues. The resulting tissue parameters subsequently served to calculate the contrast-to-noise (C/N) ratio for typical tissue interfaces as a function of the operator-variable pulse timing parameters and the data were compared with the images. Although such calculations may be useful as a protocol selection aid, it is obvious that an optimized pulse protocol can only be established for a single tissue interface. The data also reveal that a T2-discriminating pulse sequence like Carr-Purcell-Meiboom-Gill with long repetition time, generally advocated as clinically most effective, may not always be ideal.

Comparative effects of hexachloro- and hexabromobenzene on hepatic monooxygenase activity of male and female rats.

Male and female Sprague-Dawley rats were treated once with either crude or purified hexachlorobenzene (HCB) or crude or purified hexabromobenzene (HBB) at 150 mg/kg, intraperitoneally. Examination of hepatic microsomes 4 d later revealed an increase in cytochrome P-450 levels in both HCB- and HBB-pretreated animals. HBB produced a slight but statistically significant hypsochromic shift. Both HCB and HBB produced an increase in benzphetamine N-dealkylation: HCB produced a greater effect than HBB, and male rat microsomes produced more HCHO than female rat microsomes from the N-demethylation of benzphetamine. HCB and HBB both enhanced ethoxycoumarin and ethoxyresorufin O-dealkylation. Liver-to-body weight ratios were not significantly affected by pretreatment with either halogenated compound. There appeared to be no difference between the crude and purified halogenated compounds. Electrophoresis of microsomes from male rats pretreated with purified HBB indicated the presence of a band at 53,000 daltons, which was also seen in microsomes from rats pretreated with 3-methylcholanthrene. This band was absent in microsomes from rats pretreated with phenobarbital. Evidence from other laboratories has demonstrated the mixed type of P-450(s) induction after HCB administration, as does this report using enzymic and electrophoretic data.

Further structural analysis of rat liver microsomal metabolites of 2-methylnaphthalene.

The oxidative metabolites of 2-methylnaphthalene (2-MN) were extracted from rat liver microsome suspensions. One monohydroxylated and three isomeric dihydrodiol metabolites of 2-MN were isolated and purified by HPLC. The metabolites were characterized by GC-MS together with 1H Fourier transform (1HFT) NMR. The identification of a 2-MN-monohydroxylated product as 2-hydroxymethylnaphthalene was confirmed by comparison of its HPLC retention time and NMR spectrum with that of a synthetic standard. The three isomeric dihydrodiol metabolites had different HPLC retention times, fragmentation patterns, ultraviolet, and 1H NMR spectra. GC-MS of the silylated dihydrodiols revealed the consistent presence of an ion peak at m/z 320, indicative of a disilylated dihydrodiol. Analysis of the 1H FT NMR spectra revealed the metabolites to be the 3,4-dihydrodiol, 5,6-dihydrodiol, and 7,8-dihydrodiol of 2-methylnaphthalene.

Pulmonary toxicity of 2-methylnaphthalene: lack of a relationship between toxicity, dihydrodiol formation and irreversible binding to cellular macromolecules in DBA/2J mice.

Intraperitoneal doses of 2-methylnaphthalene (2-MN) have been shown to cause pulmonary toxicity in DBA/2J mice. Pretreatment with the monooxygenase inducers sodium phenobarbital and 3-methylcholanthrene (3-MC) failed to protect the DBA/2J mice from the toxic effect of 2-methylnaphthalene. Pretreatment of DBA/2J mice with the monooxygenase inhibitors, SKF 525-A and piperonyl butoxide also failed to enhance or attentuate the pulmonary lesions. Pulmonary and hepatic microsomes from DBA/2J mice metabolized 2-methylnaphthalene to three dihydrodiols, 2-naphthyl alcohol and other unidentified metabolites. Kidney microsomes produced 2-naphthyl alcohol but no detectable dihydrodiols. In comparison to control animals, hepatic microsomes from animals pretreated with sodium phenobarbital produced more of the least polar dihydrodiol, while amounts of the other two dihydrodiols were unaffected. 3-Methylcholanthrene, piperonyl butoxide and diethylmaleate failed to affect dihydrodiol formation in both pulmonary and hepatic microsomes. After the administration of a lung toxic dose (400 mg/kg, i.p.) of 2-MN, irreversible binding was highest in the liver, followed by the kidney, the lung and lastly skeletal muscle. Of the pretreatments given to the mice, only phenobarbital demonstrated a significant effect, and this elevation was apparent only in the liver. A pulmonary toxic dose of 2-MN (400 mg/kg, i.p.) administered to DBA/2J mice significantly depleted reduced GSH in the liver and lung and to a lesser extent, in the kidney. There appeared no good correlation between the pulmonary toxicity of 2-MN-dihydrodiol and/or alcohol formation or the in vivo irreversible binding to macromolecules. These results are compared with those reported previously in C57BL/6J mice.

Metabolism of 2-methylnaphthalene to isomeric dihydrodiols by hepatic microsomes of rat and rainbow trout.

The metabolism of 2-methylnaphthalene in rats (in vivo and in vitro) and rainbow trout (in vitro) has been investigated. Three isomeric dihydrodiols were formed by microsomal preparations and these were isolated and identified by high-pressure liquid chromatography and gas chromatography/mass spectroscopy. The temperature, microsomal protein content, and incubation time were varied to obtain the optimum conditions for their formation. The conversion of 2-methylnaphthalene to both monohydroxylated compounds and dihydrodiols was reduced by incubation with carbon monoxide, the omission of NADPH, or use of heat-denatured microsomes, implying the involvement of cytochrome(s) P-450-linked mixed-function oxidase activity. The three dihydrodiols obtained in vitro in microsomes from both rat and fish were identical with those compounds isolated from rat urine. Pretreatment with phenobarbital and beta-naphthoflavone selectively altered the rate of formation of specific dihydrodiols by rat liver microsomes. Although phenobarbital had no significant effect on the rate of dihydrodiol formation in trout liver microsomes, beta-naphthoflavone was a strong inducer and its selectivity in increasing the rate of dihydrodiol formation was similar to that seen with rat liver microsomes.