Brain atrophy in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis: longitudinal quantitative analysis

PURPOSE: To determine annual rates of volumetric changes in the whole-brain parenchyma of patients with relapsing-remitting and secondary progressive multiple sclerosis (MS) and test the hypothesis that these changes correlate with clinical disability. MATERIALS AND METHODS: A computer-assisted segmentation technique with thin-section magnetic resonance (MR) imaging was used in 36 patients with MS (27 relapsing-remitting, nine secondary progressive) and in 20 control subjects to quantify brain and cerebrospinal fluid volumes. To determine the degree of brain atrophy, the percentage brain parenchyma volume (PBV) relative to that of intracranial contents was calculated. RESULTS: At the beginning of the study, the PBV was smaller in the MS group than in the control group (P = .007); brain parenchyma volumes were similar. The median rate of brain volume loss was 17.3 mL per year in patients with relapsing-remitting MS and 23.6 mL per year in those with secondary progressive MS. There was a negative correlation between brain atrophy and Expanded Disability Status Scale (EDSS) score in patients with secondary progressive MS (r = -0.69, P = .004) and no correlation in patients with relapsing-remitting MS. T2 lesion volume did not correlate with brain atrophy in either group. CONCLUSION: The correlation between brain atrophy and EDSS score was better in patients with secondary progressive MS than in those with relapsing-remitting MS.     

The effect of gadolinium-enhancing lesions on whole brain atrophy in relapsing-remitting MS

OBJECTIVE: To determine the relationship between gadolinium-enhancing lesions and changes in whole brain parenchymal volume in patients with relapsing-remitting MS, and to test the hypothesis that gadolinium enhancement is a predictor of whole brain atrophy. METHODS: Twenty-four patients with clinically definite MS were imaged over 2 years. A computer-assisted segmentation technique based on high-resolution MRI was used to quantify gadolinium-enhancing T1 lesion volume and brain parenchyma and CSF volumes. Percent brain parenchymal volume (PBV) relative to the total intracranial volume was calculated, and changes in PBV were used to represent the degree of whole brain atrophy over 2 years. RESULTS: PBV at baseline was dependent on duration of MS, and a significant decrease in PBV was observed over the course of the study. Changes in enhanced T1 lesion load failed to correlate with changes in PBV, and multiple regression analyses determined that enhanced T1 lesion load at baseline was not a significant predictor of subsequent change in PBV. CONCLUSIONS: MR visible inflammation as demonstrated by enhanced T1 lesions is not a significant factor in the pathogenesis of whole brain atrophy in relapsing-remitting MS, suggesting that a more global pathologic process is responsible for the loss of brain parenchymal volume.     

Surface and volume rendering in three-dimensional imaging: A comparison

Many surface rendering techniques are currently available for the three-dimensional display of structure data captured by imaging devices. Comparatively fewer volume rendering techniques are also available for the same purpose. The relative performance of these two methodologies in visualization tasks has been a subject of much discussion recently. Although it is very desirable to establish, based on observer studies, objective guidelines stating the relative merits of the two methodologies even for specific situations, it is impossible to conduct meaningful observer studies that take into account the numerousness of the techniques in each methodology, and within each technique, the numerousness of the parameters and their values that control the outcome of the technique. Our aim in this article is to compare the two methodologies purely on a technical basis in an attempt to understand their common weaknesses and disparate strengths. The purpose of this article is twofold--to report a new surface rendering technique and to compare it with two volume rendering techniques reported recently in the literature. The bases of comparison are: ability to portray thin bones; clarity of portrayal of sutures, fractures, fine textures, and gyrations; smoothness of natural ridges and silhouettes; and computational time and storage requirements. We analyze the underlying algorithms to study how they behave under each of these comparative criteria. Our conclusion is that, at the current state of development, the surface method has a slight edge over the volume methods for portrayal of information of the type described above and a significant advantage considering time and storage requirements, for implementations in identical environments.     

Possible role of tumor necrosis factor-alpha in erythropoietic suppression by endotoxin and granulocyte/macrophage colony-stimulating factor

Injection of bacterial endotoxin or granulocyte/macrophage colony-stimulating factor (GM-CSF) into exhypoxic polycythemic mice simultaneously with erythropoietin (EPO) suppressed erythroid cell formation, as monitored by ⁵⁹Fe incorporation into circulating red blood cells. This effect was dose-dependent and time-dependent. GM-CSF did not inhibit erythroid cell formation directly, as the antibody to the GM-CSF did not neutralize the effect of endotoxin, the inducer of GM-CSF. The suppression of both agents could be partially corrected by prior injection of a monoclonal antibody to tumor necrosis factor α (anti-TNFα). These results indicate that the suppression of EPO-induced erythroid cell formation by endotoxin and GM-CSF was due in part to the production of TNFα. © 1996 Wiley-Liss, Inc.     

Sub-nanograin metal based high efficiency multilayer reflective optics for high energies

The present finding illuminates the physics of the formation of interfaces of metal based hetero-structures near layer continuous limit as an approach to develop high-efficiency W/B₄C multilayer (ML) optics with ML periodicity varying d = 1.86–1.23 nm at a fixed number of layer pairs N = 400. The microstructure of metal layers is tailored near the onset of grain growth to control the surface density of grains resulting in small average sizes of grains to sub-nanometers. This generates concurrently desirable atomically sharp interfaces, high optical contrast, and desirable stress properties over a large number of periods, which have evidence through the developed ML optics. We demonstrate significantly high reflectivities of ML optics measured in the energy range 10–20 keV, except for d = 1.23 nm due to quasi-continuous layers. The reflectivities at soft gamma-rays are predicted.

The present finding illuminates the physics of the formation of interfaces of metal based hetero-structures near layer continuous limit as an approach to develop high-efficiency W/B₄C multilayer optics with varying periods at a fixed large layer pairs.     

Generation and characterization of a neutralizing monoclonal antibody against erythroid cell stimulating factor

Erythroid cell stimulating factor (ESF) is present in mouse serum and has been reported to function in concert with erythropoietin (EPO) in the formation of erythroid cells in in vitro culture systems. We report here the generation and characterization of a monoclonal antibody (MAb) directed against ESF, with potent anti-ESF-neutralizing activity. A hybridoma-producing MAb to ESF was selected following enzyme-linked immunosorbent assay (ELISA)-based screening of 270 colonies obtained from a fusion of immunized mouse splenocytes with NS1 myeloma cells. Western blot analyses of mouse serum using this antibody specifically detected a single protein (approximate molecular weight of 60 kDa and 120 kDa, under reducing and nonreducing conditions, respectively) corresponding to ESF, with no reactivity to EPO. Furthermore, this MAb demonstrated reactivity to a protein similar in molecular mass, across species, showing reactivity in sera obtained from human, horse, goat, guinea pig, rabbit, and rat. Immuno-chemical characterization demonstrated this antibody to be of IgG3 isotype, bearing kappa light chains. Injection of this monoclonal anti-ESF antibody to exhypoxic polycythemic mice at 6 and 24 h after EPO injection significantly reduced 59Fe incorporation into red blood cells, demonstrating its ability to neutralize in vivo erythropoiesis in our mouse model system. Thus, this novel erythroid cell-specific MAb will be an invaluable tool for further delineating the physiological role of ESF in in vivo erythropoiesis.     

The effect of ankle ligament damage and surgical reconstructions on the mechanics of the ankle and subtalar joints revealed by three-dimensional stress MRI.

Common image-based diagnostic techniques used to detect ankle ligament injuries or the effects of those injuries (e.g., mechanical instability) include magnetic resonance imaging (MRI) and stress radiography. Each of these techniques has limitations. The interpretation of the results obtained through stress radiography, a two-dimensional technique, is highly controversial. MRI can facilitate visualization of soft tissue, but three-dimensional visualization of the full length of the ligaments or detecting partial ligament damage is difficult. This work is part of a long-term study aimed at improving the diagnostic ability of MRI by utilizing it not only to visualize the ligaments but also to detect the mechanical instability produced at the ankle and subtalar joints due to ligament damage. The goal of the present study was to evaluate the ability of a previously developed technique called 3D stress MRI (sMRI) to detect in vitro the effect of damage to the lateral collateral ligaments and the stabilizing effect produced by two common surgical reconstruction techniques. MRI data were collected from eight cadaver limbs in a MR compatible ankle-loading device in neutral, inversion, and anterior drawer. Each specimen was tested intact, after cutting the anterior talo-fibular ligament followed by the calcaneo-fibular ligament and after applying two reconstructions. Ligament injuries produced significant changes in the response of the ankle and subtalar joints to load as detected by the 3D stress MRI technique. Both surgical procedures restored mechanical stability to the joints but they differed in the amount and type of stabilization achieved. We concluded that 3D sMRI can extend the diagnostic power of MRI from the current practice of slice-by-slice visualization to the assessment of mechanical function, the compromise in this function due to injury, and the effects of surgery.     

Anovestibular fistula in adults: a rare presentation

Adult presentation of anorectal malformations (ARM) is rare. Most of these anomalies are diagnosed and corrected at birth or shortly thereafter. We will present two cases of anovestibular fistula presenting in adulthood. One case is a woman with a history of passing stools through the vagina after marriage and the other case is a woman with a history of chronic constipation since childhood. Case 1 was treated with limited anterior sagittal anorectoplasty, and case 2 was treated with limited posterior sagittal anorectoplasty. Total correction was achieved both anatomically and physiologically after surgery. The reporting of this information should increase the awareness of this disease among surgeons treating adults.