A Novel MRI Biomarker of Spinal Cord White Matter Injury: T2*-Weighted White Matter to Gray Matter Signal Intensity Ratio.

BACKGROUND AND PURPOSE: T2*-weighted imaging provides sharp contrast between spinal cord GM and WM, allowing their segmentation and cross-sectional area measurement. Injured WM demonstrates T2*WI hyperintensity but requires normalization for quantitative use. We introduce T2*WI WM/GM signal-intensity ratio and compare it against cross-sectional area, the DTI metric fractional anisotropy, and magnetization transfer ratio in degenerative cervical myelopathy. MATERIALS AND METHODS: Fifty-eight patients with degenerative cervical myelopathy and 40 healthy subjects underwent 3T MR imaging, covering C1-C7. Metrics were automatically extracted at maximally compressed and uncompressed rostral/caudal levels. Normalized metrics were compared with t tests, area under the curve, and logistic regression. Relationships with clinical measures were analyzed by using Pearson correlation and multiple linear regression. RESULTS: The maximally compressed level cross-sectional area demonstrated superior differences (P = 1 × 10-13), diagnostic accuracy (area under the curve = 0.890), and univariate correlation with the modified Japanese Orthopedic Association score (0.66). T2*WI WM/GM showed strong differences (rostral: P = 8 × 10-7; maximally compressed level: P = 1 × 10-11; caudal: P = 1 × 10-4), correlations (modified Japanese Orthopedic Association score; rostral: -0.52; maximally compressed level: -0.59; caudal: -0.36), and diagnostic accuracy (rostral: 0.775; maximally compressed level: 0.860; caudal: 0.721), outperforming fractional anisotropy and magnetization transfer ratio in most comparisons and cross-sectional area at rostral/caudal levels. Rostral T2*WI WM/GM showed the strongest correlations with focal motor (-0.45) and sensory (-0.49) deficits and was the strongest independent predictor of the modified Japanese Orthopedic Association score (P = .01) and diagnosis (P = .02) in multivariate models (R2 = 0.59, P = 8 × 10-13; area under the curve = 0.954, respectively). CONCLUSIONS: T2*WI WM/GM shows promise as a novel biomarker of WM injury. It detects damage in compressed and uncompressed regions and contributes substantially to multivariate models for diagnosis and correlation with impairment. Our multiparametric approach overcomes limitations of individual measures, having the potential to improve diagnostics, monitor progression, and predict outcomes.

Clinically Feasible Microstructural MRI to Quantify Cervical Spinal Cord Tissue Injury Using DTI, MT, and T2*-Weighted Imaging: Assessment of Normative Data and Reliability.

BACKGROUND AND PURPOSE: DTI, magnetization transfer, T2*-weighted imaging, and cross-sectional area can quantify aspects of spinal cord microstructure. However, clinical adoption remains elusive due to complex acquisitions, cumbersome analysis, limited reliability, and wide ranges of normal values. We propose a simple multiparametric protocol with automated analysis and report normative data, analysis of confounding variables, and reliability. MATERIALS AND METHODS: Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in <35 minutes using standard hardware and pulse sequences. Cross-sectional area, fractional anisotropy, magnetization transfer ratio, and T2*WI WM/GM signal intensity ratio were calculated. Relationships between MR imaging metrics and age, sex, height, weight, cervical cord length, and rostrocaudal level were analyzed. Test-retest coefficient of variation measured reliability in 24 DTI, 17 magnetization transfer, and 16 T2*WI datasets. DTI with and without cardiac triggering was compared in 10 subjects. RESULTS: T2*WI WM/GM showed lower intersubject coefficient of variation (3.5%) compared with magnetization transfer ratio (5.8%), fractional anisotropy (6.0%), and cross-sectional area (12.2%). Linear correction of cross-sectional area with cervical cord length, fractional anisotropy with age, and magnetization transfer ratio with age and height led to decreased coefficients of variation (4.8%, 5.4%, and 10.2%, respectively). Acceptable reliability was achieved for all metrics/levels (test-retest coefficient of variation < 5%), with T2*WI WM/GM comparing favorably with fractional anisotropy and magnetization transfer ratio. DTI with and without cardiac triggering showed no significant differences for fractional anisotropy and test-retest coefficient of variation. CONCLUSIONS: Reliable multiparametric assessment of spinal cord microstructure is possible by using clinically suitable methods. These results establish normalization procedures and pave the way for clinical studies, with the potential for improving diagnostics, objectively monitoring disease progression, and predicting outcomes in spinal pathologies.

Dose-response to tibric acid: a new hypolipidemic drug in type IV hyperlipoproteinemia.

This double-blind study compares the effects of tibric acid at four different doses to that of placebo in type IV hyperlipidemic patients. Fifty patients, divided at random in five groups of 10 patients each, received one of the following treatments: placebo, tibric acid 500 mg, 750 mg, 1,000 mg, or 1,250 mg per 24 hr. The data suggest that the 1,000 mg and the 1,250 mg doses are effective in lowering the serum triglyceride levels after 6 wk of treatment; the effect on total cholesterol is less pronouced. No effect is observed on the concentration of serum esterified cholesterol, phospholipids, and free fatty acids. It is also shown that in the dose range studied, the best fitting curve defining the four mean values of triglycerides and total cholesterol obtained with the four active treatments did not deviate significantly from linearity. Due to lack of toxicity, tibric acid may be useful in the treatment of type IV hyperlipoproteinemia.

Comparative study of gastrointestinal microbleeding caused by aspirin, fenbufen, and placebo.

Fifty volunteers, randomly divided into five groups, received placebo, fenbufen, or aspirin at dosages used in treating osteoarthritis and rheumatoid arthritis (fenbufen, 600 or 900 mg daily; aspirin, 3.6 g daily) for 28 days. Following radioactive chromium labeling of red cells in each subject, stool specimens were collected weekly for determination of blood loss by radioisotope procedure. Statistical analyses demonstrated no significant differences in gastrointestinal microbleeding between subjects who received fenbufen (600 or 900 mg daily) and those who received placebo. Conversely, there were significant (p less than 0.01) differences in microbleeding between subjects given aspirin and those given either dosage of fenbufen or placebo.

Gastrointestinal blood loss of oxaprozin and aspirin with placebo control.

The objective of this study was to compare the effects of oxaprozin (4,5-diphenyl-2-oxazolepropionic acid), a nonsteroidal, antiinflammatory compound, and aspirin in a double-blind, placebo-controlled study to estimate gastrointestinal bleeding. The determination of fecal blood loss was made quantitatively by the use of the radioactive (51Cr) technique. During the first week, subjects were controlled with and without placebo. At the end of the second week, the subjects were divided and randomly assigned to one of three groups; 10 received 1200 mg oxaprozin (600 mg twice daily), 11 received 3900 mg aspirin (975 mg four times a day), and the remaining 8 subjects received placebo for two weeks. During the last two weeks, all received placebo again. A statistical analysis of variance showed that there were no statistical differences between the groups during the first and last two weeks of placebo therapy. During the active treatment period, weeks 3 and 4, there were statistically significant differences among the three groups. The mean blood loss during week 3 was significantly greater for the aspirin group, 8.8 ml/day, than the oxaprozin group, 3.3 ml/day (P less than 0.05), and the placebo group, 1.4 ml/day (P less than 0.001). The smaller difference between oxaprozin and placebo was also significant (P less than 0.05). During the fourth week, the mean daily blood loss among oxaprozin patients had decreased to 2.3 ml/day, and no statistically significant difference from placebo (1.1 ml/day) was found.

Urorectodynamics in patients with colonic inertia.

Sixteen female patients with colonic inertia and 12 control women underwent manometric evaluation of their bladder and rectal cavities. After subcutaneous injection of 0.035 mg./Kg. bethanechol, bladder intraluminal pressure increased by over 15 cm. water in 5 patients (31 per cent) and in none of the control group; maximal pressure after injection was 11.5 +/- 1.6 cm. H2O (mean +/- SE) in patients and 8.5 +/- 1 in controls (p less than 0.025). The intraluminal rectal pressure reached 23 +/- 4 cm. H2O in patients and only 11.9 +/- 1.4 in controls (p less than 0.0025). Time taken to reach a peak pressure was faster in patients both in bladder (17.4 +/- 0.7 vs. 19.8 +/- 1.2 minutes; p less than 0.01) and in the rectum 914.6 +/- 0.8 vs. 16.3 +/- 1.2; p less than 0.025). These findings and the clinical presentation suggest an autonomic neuropathic lesion in this group of patients.

Hyperventilation and vertigo.

An electronystagmographic study was conducted on 19 normal subjects, in order to observe whether the subjective sensation of dizziness provoked by hyperventilation could be confirmed objectively by nystagmus. Each of them had two electronystagmograms, the first being a routine ENG and the second a repetition of the first, but with additional periods of 90 sec. of hyperventilation at certain precise pre-determined moments of the test. Hyperventilation was not shown to have significant effect on the slow phase of post caloric nystagmus; however, it increased significantly (p = 0.061) the number of positions in which nystagmus was elicited. Hyperventilation would have such an effect in producing a certain degree of cerebral hypoxia through cerebral vasoconstriction and the Bohr effect.

Radiographic evaluation of the symptom-producing adenoid.

Adenoid hypertrophy has several variable symptoms. In this study, symptoms were divided into minor and major. A lateral radiograph of the nasopharynx was performed in 114 patients to study the superior and antroadenoid diameters. With proper statistical analysis, a correlation was made between the various clinical groups (scores) and the adenoid measurements. Our results support Hibbert's findings that the antroadenoid width is a better indicator of the symptom-producing adenoid than adenoid mass measurements with their loosely defined norms. A thorough history and physical examination remain paramount in the diagnosis and management of adenoid hypertrophy.

Adjuvant arthritis: influence of the adjuvant volume and composition on the established arthritis.

Adjuvant arthritis remains an interesting model for the evaluation of therapeutic agents and for the study of inflammatory mechanisms. The severity and time course of the primary nonspecific inflammation and of the induced polyarthritis are influenced by the composition and volume of the injected adjuvant. The injection of complete adjuvant produces always an oedema which is much greater than the sum of the oedemas induced by mineral oil or mycobacteria alone. In Lewis rats, highly susceptible to adjuvant arthritis, the intensity of the induced lesions increases with the injected oil volume and for equal volumes is maximal with 500 micrograms of Mycobacterium butyricum. In the injected paw the specific immune character of the inflammation is more important when a small volume of adjuvant is used and is maximal for 500 micrograms of mycobacteria in 0.1 ml of mineral oil.

Adjuvant arthritis: influence of the adjuvant volume and composition on the non-specific inflammation.

Adjuvant-induced arthritis is an animal model of chronic inflammatory disease widely used in anti-inflammatory and immunosuppressive drugs testing. When the development and the inhibition of the induced arthritis are measured by the injected paw oedema, it is difficult to delineate the immunological contribution from the persistent non-specific primary section. To study the influence of volume and composition of the injected adjuvant upon the primary non-specific inflammation, we devised a 3X4 factorial experiment on a strain of inbred rats with a low susceptibility to adjuvant-induced arthritis. The injection of mineral oil alone produces a persistent oedema. The injection of mycobacteriae in suspension in saline induces a rapid inflammatory response followed by a fast decrease of the oedema. When complete adjuvant is used, there is always a very strong interaction between the effects of the two components of the adjuvant, i.e. the measured oedemas are much greater than the calculated values, For a given injected volume, the inflammation is maximum when the concentration of mycobacteriae is 2.5 mg/ml. All the rats injected with complete adjuvant present a transient oedema of the non-injected hind paw. This oedema is very small and proportional to the amount of mycobacteria injected.

[Comparison of masked and endogenous depression using psychometric scales, endocrinological markers and pharmacological responses. Masked depression versus endogenous depression]. / Comparaison de la dépression masquée et de la dépression endogène à l'aide d'échelles psychométriques, de marqueurs endocrinologiques et de réponses pharmacologiques. Dépression masquée versus dépression endogène.

Masked depression refers to a concept of a phenomenological state, either endogenous or psychogenic where somatic symptoms replace sadness: Thirty patients were evaluated by RDC (22 endogenous and 8 masked depressions) wherein in the latter dysphoria was replaced by a nonreactive persistent somatic complaint. They were rated on Beck and Hamilton Depression Scales, on Hamilton and Trait-State Anxiety Scales and the NOSIE. All patients presented with insomnia, anorexia, loss of weight, diminished libido and anhedonia. Initial ratings were similar for both diagnostic groups except for a significantly higher agitation factor and lower retardation in masked depression. Although 59.9 percent of the subjects are positive on the dexamethasone test, only 1 masked depression did not suppress secretion of cortisol. After a randomized 30-day drug trial where patients were assigned to Clomipramine or Desipramine, patients in both groups show significant improvement on rating scales but diagnostic group drug treatment interaction exists on anxiety and agitation criteria.