Biomedical subjects

C R Guttmann

Publications and source records attributed to C R Guttmann.

At least 19 recordsLinked to original sources

PubMed1999

Changes in serum levels of ICAM and TNF-R correlate with disease activity in multiple sclerosis.

OBJECTIVE: To study the change in serum levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble tumor necrosis factor receptors (sTNF-Rs) in MS patients in relation to clinical disease activity and changes on brain MRI. BACKGROUND: Circulating forms of adhesion molecules or soluble receptors may be released from cells as a consequence of activation and may be useful markers for inflammation. METHODS: During a prospective longitudinal study over 1 year, 40 patients with MS underwent frequent imaging of the brain (22 MR images per patient) at the time of blood sampling as well as monthly neurologic examinations, and scoring on Kurtzke's Expanded Disability Status Scale (EDSS) and ambulation index (AI). RESULTS: Patients with relapsing-progressive disease had the highest levels of sICAM-1 whereas patients with progressive disease had the highest levels of sTNF-Rs. Fluctuations in sICAM-1 correlated with the occurrence of attacks in patients with relapsing and relapsing-progressive disease. In patients with relapsing-progressive MS, an increase in sICAM-1 level preceded the appearance of new gadolinium (Gd) enhancing lesions on MRI. In patients with progressive disease, an increase in sTNF-R p55 level preceded the appearance of new Gd enhancing lesions on MRI, whereas a decrease in sICAM-1 levels correlated with the appearance of new Gd enhancing lesions. CONCLUSIONS: These results demonstrate a linkage between sICAM-1 and sTNF-R levels and disease activity in MS. Furthermore, patients with progressive disease appear to have a different immunologic stage of disease in which immune changes are tightly linked with changes on MRI. The demonstration of a correlation in individual patients between immunologic events and changes in disease activity has implications for monitoring patients undergoing treatment and for monitoring disease progression.

Adult↗

PubMed1999

Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: a meta-analysis. Gadolinium MRI Meta-analysis Group.

BACKGROUND: Reliable prognostic factors are lacking for multiple sclerosis (MS). Gadolinium enhancement in magnetic resonance imaging (MRI) of the brain detects with high sensitivity disturbance of the blood-brain barrier, an early event in the development of inflammatory lesions in MS. To investigate the prognostic value of gadolinium-enhanced MRI, we did a meta-analysis of longitudinal MRI studies. METHODS: From the members of MAGNIMS (European Magnetic Resonance Network in Multiple Sclerosis) and additional centres in the USA, we collected data from five natural-course studies and four placebo groups of clinical trials completed between 1992 and 1995. We included a total of 307 patients, 237 with relapsing disease course and 70 with secondary progressive disease course. We investigated by regression analysis the relation between initial count of gadolinium-enhancing lesions and subsequent worsening of disability or impairment as measured by the expanded disability status scale (EDSS) and relapse rate. FINDINGS: The relapse rate in the first year was predicted with moderate ability by the mean number of gadolinium-enhancing lesions in monthly scans during the first 6 months (relative risk per five lesions 1.13, p=0.023). The predictive value of the number of gadolinium-enhancing lesions in one baseline scan was less strong. The best predictor for relapse rate was the variation (SD) of lesion counts in the first six monthly scans which allowed an estimate of relapse in the first year (relative risk 1.2, p=0.020) and in the second year (risk ratio=1.59, p=0.010). Neither the initial scan nor monthly scans over six months were predictive of change in the EDSS in the subsequent 12 months or 24 months. The mean of gadolinium-enhancing-lesion counts in the first six monthly scans was weakly predictive of EDSS change after 1 year (odds ratio=1.34, p=0.082) and 2 years (odds ratio=1.65, p=0.049). INTERPRETATION: Although disturbance of the blood-brain barrier as shown by gadolinium enhancement in MRI is a predictor of the occurrence of relapses, it is not a strong predictor of the development of cumulative impairment or disability. This discrepancy supports the idea that variant pathogenetic mechanisms are operative in the occurrence of relapses and in the development of long-term disability in MS.

Adolescent↗

PubMed1999

Multi-component apparent diffusion coefficients in human brain.

The signal decay with increasing b-factor at fixed echo time from brain tissue in vivo has been measured using a line scan Stejskal-Tanner spin echo diffusion approach in eight healthy adult volunteers. The use of a 175 ms echo time and maximum gradient strengths of 10 mT/m allowed 64 b-factors to be sampled, ranging from 5 to 6000 s/ mm2, a maximum some three times larger than that typically used for diffusion imaging. The signal decay with b-factor over this extended range showed a decidedly non-exponential behavior well-suited to biexponential modeling. Statistical analyses of the fitted biexponential parameters from over 125 brain voxels (15 x 15 x 1 mm3 volume) per volunteer yielded a mean volume fraction of 0.74 which decayed with a typical apparent diffusion coefficient around 1.4 microm2/ms. The remaining fraction had an apparent diffusion coefficient of approximately 0.25 microm2/ms. Simple models which might explain the non-exponential behavior, such as intra- and extracellular water compartmentation with slow exchange, appear inadequate for a complete description. For typical diffusion imaging with b-factors below 2000 s/mm2, the standard model of monoexponential signal decay with b-factor, apparent diffusion coefficient values around 0.7 microm2/ms, and a sensitivity to diffusion gradient direction may appear appropriate. Over a more extended but readily accessible b-factor range, however, the complexity of brain signal decay with b-factor increases, offering a greater parametrization of the water diffusion process for tissue characterization.

Adult↗

PubMed1999

Quantitative follow-up of patients with multiple sclerosis using MRI: reproducibility.

The reproducibility of an automated method for estimating the volume of white matter abnormalities on brain magnetic resonance (MR) images of multiple sclerosis (MS) patients was evaluated. Twenty MS patients underwent MR imaging twice within 30 minutes. Measurement variability is introduced mainly by MRI acquisition and image registration procedures, which demonstrate significantly worse reproducibility than the image segmentation. The correction of partial volume artifacts is essential for sensitive measurements of overall lesion burden. The average lesion volume difference (bias) between two MR exams of the same MS patient (N = 20) was 0.05 cm3, with a 95% confidence interval between -0.17 and +0.28 cm3, suggesting that the proposed measurement system is suitable for clinical follow-up trials, even in relatively small patient cohorts. The limits of agreement for lesion volume were between -1.3 and +1.5 cm3, implying that in individual patients changes in lesion load need to be at least this large to be detected reliably. This automated method for estimating lesion burden is a reliable tool for the evaluation of MS progression and exacerbation in patient cohorts and potentially also in individual patients.

Adjuvants, Immunologic↗

PubMed1999

Quantitative follow-up of patients with multiple sclerosis using MRI: technical aspects.

A highly reproducible automated procedure for quantitative analysis of serial brain magnetic resonance (MR) images was developed for use in patients with multiple sclerosis (MS). The intracranial cavity (ICC) was identified on standard dual-echo spin-echo brain MR images using a supervised automated procedure. MR images obtained from one MS patient at 24 time points in the course of a 1-year follow-up were aligned with the images of one of the time points. Next, the contents of the ICC in each MR exam were segmented into four tissues, using a self-adaptive statistical algorithm. Misclassifications due to partial voluming were corrected using a combination of morphologic operators and connectivity criteria. Finally, a connectivity detection algorithm was used to separate the tissue classified as lesions into individual entities. Registration, classification of the contents of the ICC, and identification of individual lesions are fully automatic. Only identification of the ICC requires operator interaction. In each MR exam, the program estimated volumes for the ICC, gray matter (GM), white matter (WM), white matter lesions (WML), and cerebrospinal fluid (CSF). The reproducibility of the system was superior to that of supervised segmentation, as evidenced by the coefficient of variation: CSF supervised 45.9% vs. automated 7.7%, GM 16.0% vs. 1.4%, WM 15.7% vs. 1.3%, and WML 39.5% vs 52.0%. Our results demonstrate that this computerized procedure allows routine reproducible quantitative analysis of large serial MRI data sets.

Adult↗

PubMed1999

Functional magnetic resonance imaging using non-Fourier, spatially selective radiofrequency encoding.

A new method for functional magnetic resonance imaging (fMRI) employing non-Fourier encoding using spatially selective radiofrequency (RF) excitation is presented. The method uses manipulation of spatially selective RF pulses to encode spins in the slice-select direction. The method has several advantages over standard multislice approaches. It provides a simple means for monitoring irregularly distributed sections throughout a volume without the need to encode the whole volume. It offers the potential for increased signal-to-noise ratio if an appropriate basis is used for encoding. With a unique design of excitation pulses, it also appears possible to significantly reduce in-flow effects. An interleaved echo-planar imaging (EPI) sequence was adapted for non-Fourier encoding in the slice-select direction and was implemented on a conventional 1.5-Telsa system. The method was then used for functional mapping of the visual and motor areas where significant reduction of in-flow effect was demonstrated. This approach can be adapted to other imaging sequences that are used for fMRI, such as single-shot EPI.

Adult↗

PubMed1999

Spin-Echo planar spectroscopic imaging for fast lipid characterization in bone marrow.

Lipid characterization of bone marrow in vivo with proton magnetic resonance spectroscopy was performed using Spin-Echo Planar Spectroscopic Imaging sequences. The methods are shown capable of rapidly generating two-dimensional chemical shift imaging data sets suitable for measuring lipid indices that reflect unsaturation levels among triglycerides, as demonstrated in oil phantoms and bone marrow from a healthy volunteer. The volume coverage, spatial resolution, acquisition speed, and spectral characteristics of Spin-Echo Planar Spectroscopic Imaging should make it attractive for clinical studies of diseases affecting normal lipid chemical composition.

Adult↗

PubMed1998

White matter changes with normal aging.

We evaluated brain tissue compartments in 72 healthy volunteers between the ages of 18 and 81 years with quantitative MRI. The intracranial fraction of white matter was significantly lower in the age categories above 59 years. The CSF fraction increased significantly with age, consistent with previous reports. The intracranial percentage of gray matter decreased somewhat with age, but there was no significant difference between the youngest subjects and the subjects above 59. A covariance adjustment for the volume of hyperintensities did not alter the foregoing results. The intracranial percentage of white matter volume was strongly correlated with the percentage volume of CSF. The finding of a highly significant decrease with age in white matter, in the absence of a substantial decrease in gray matter, is consistent with recent neuropathologic reports in humans and nonhuman primates.

Adolescent↗

PubMed1997

Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis.

OBJECTIVE: To assess the correlation between cognitive dysfunction and disease burden in multiple sclerosis (MS) during a 1-year period. DESIGN: The Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis was performed at entrance and 1 year. Patients underwent at least 20 proton density (range, 20-24) and T2-weighted axial magnetic resonance imaging (MRI) brain scans except for stable patients who were scanned monthly. Magnetic resonance imaging was evaluated using computer-automated, 3-dimensional volumetric analysis. SETTING: A research clinic of a university hospital. PATIENTS: Forty-four patients with MS of the following disease categories: relapsing-remitting (14), relapsing-remitting progressive (12), chronic progressive (13), and stable (5). MAIN OUTCOME MEASURES: The relationships between scores on the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis and 2 MRI measures (total lesion volume and brain to intracranial cavity volume ratio) were assessed using linear regression. These MRI measures were also compared with cognitive status at 1 year using analysis of variance. RESULTS: Overall, there was no decline in mean cognitive test performance during 1 year. Significant correlations were found between baseline neuropsychological test scores of nonverbal memory, information-processing speed, and attention and both MRI measures. Patients with chronic progressive MS demonstrated the strongest correlations. At 1 year, change in information-processing speed and attention correlated with change in total lesion volume. The mean increase in total lesion volume was 5.7 mL for 4 patients whose cognitive status worsened compared with 0.4 mL for 19 patients who improved and 0.5 mL for 21 patients who remained stable. CONCLUSIONS: During a 1-year period mean cognitive performance did not worsen. Automated volumetric MRI measures of total lesion volume and brain to intracranial cavity volume ratio correlated with neuropsychological performance, especially in patients with chronic progressive MS. Worsening MRI lesion burden correlated with cognitive decline.

Adult↗

PubMed1997

3D localization of surface 10-20 EEG electrodes on high resolution anatomical MR images.

A method to visualize surface EEG electrodes on conventional high-resolution magnetic resonance (MR) images is presented. Because conventional silver or gold electrodes generate an insignificant artifactual signal signature in MR images, a plastic capsule filled with gadolinium-doped water was designed to mold onto each electrode, thereby outlining the electrode surfaces as a negative imprint on MR images. MR images of the head with capsules affixed clearly demonstrated the location and shape of the electrodes. Selected cranial tissues were identified by using semi-automatic image segmentation to determine their three-dimensional spatial relationship to the electrodes. Such representations could be used as a starting point for more precise EEG source localization modeling applicable to individual patients.

Brain↗

PubMed1996

A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy.

During 24 weeks of hydroxyurea treatment, we monitored red blood cell (RBC) parameters in three patients with sickle cell disease, including F-cell and F-reticulocyte profiles, distributions of delay times for intracellular polymerization, sickle erythrocyte adherence to human umbilical vein endothelial cells in a laminar flow chamber, RBC phthalate density profiles, mean corpuscular hemoglobin concentration and cation content, reticulocyte mean corpuscular hemoglobin concentration, 1H-nuclear magnetic resonance transverse relaxation rates of packed RBCs, and plasma membrane lateral and rotational mobilities of band 3 and glycophorins. Hydroxyurea increases the fraction of cells with sufficiently long delay times to escape the microcirculation before polymerization begins. Furthermore, high pretreatment adherence to human umbilical vein endothelial cells of sickle RBCs decreased to normal after only 2 weeks of hydroxyurea treatment, preceding the increase in fetal hemoglobin levels. The lower adhesion of sickle RBCs to endothelium would facilitate escape from the microcirculation before polymerization begins. Hydroxyurea shifted several biochemical and biophysical parameters of sickle erythrocytes toward values observed with hemoglobin SC disease, suggesting that hydroxyurea moderates sickle cell disease toward the milder, but still clinically significant, hemoglobin SC disease. The 50% reduction in sickle crises documented in the Multicenter Study of Hydroxyurea in Sickle Cell Disease is consistent with this degree of erythrocyte improvement.

Adult↗

PubMed1996

Triexponential decomposition of 1H spin-lattice relaxation decay curves of paramagnetically doped red cell suspensions at 7 T.

The spin-lattice relaxation behaviour of protons in paramagnetically doped red cell suspensions at two haematocrit levels has been studied using high-field (7 T) inversion recovery data. The resulting relaxation decay curves were found to be best characterized by triexponential functions. The two-site exchange model, generally applied to biexponential relaxation data in calculating red cell water exchange parameters, was applied to the two fastest-relaxing fractions of the triexponential fits. The intracellular to extracellular water exchange rates so obtained were in good agreement with literature values. Additional exchange parameters including intracellular and extracellular water volume fractions and extracellular relaxation rates were also calculated directly from the relaxation data and found to be consistent with sample haematocrits and with independent relaxation rate measurements of the resuspension medium. The small-amplitude, slowly relaxing third component recovered from the triexponential fits of the relaxation data is attributed to intracellular haemoglobin protons.

Adult↗

PubMed1995

Automatic identification of gray matter structures from MRI to improve the segmentation of white matter lesions.

The segmentation of MRI scans of patients with white matter lesions (WML) is difficult because the MRI characteristics of WML are similar to those of gray matter. Intensity-based statistical classification techniques misclassify some WML as gray matter and some gray matter as WML. We developed a fast elastic matching algorithm that warps a reference data set containing information about the location of the gray matter into the approximate shape of the patient's brain. The region of white matter was segmented after segmenting the cortex and deep gray matter structures. The cortex was identified by using a three-dimensional, region-growing algorithm that was constrained by anatomical, intensity gradient, and tissue class parameters. White matter and WML were then segmented without interference from gray matter by using a two-class minimum-distance classifier. Analysis of double-echo spin-echo MRI scans of 16 patients with clinically determined multiple sclerosis (MS) was carried out. The segmentation of the cortex and deep gray matter structures provided anatomical context. This was found to improve the segmentation of MS lesions by allowing correct classification of the white matter region despite the overlapping tissue class distributions of gray matter and MS lesion.

Algorithms↗

PubMed1995

In vivo characterization of cytotoxic intracellular edema by multicomponent analysis of transverse magnetization decay curves.

RATIONALE AND OBJECTIVES: We investigated the multicompartmental nature of T2 decay in a specific white matter edema model. METHODS: Triethyltin (TET) intoxication was produced in six male New Zealand White rabbits. Images were obtained over the 23-day study duration using a 64-echo Carr-Purcell-Meiboom-Gill (CPMG) sequence (repetition time = 3000 msec, echo time = 20 msec). T2 decay curves were extracted from 0.7 x 0.7 x 3.0 mm3 voxels in the corpus callosum and contiguous white matter tracts, cortex, thalamic nuclei, hypothalamic nuclei, and the masseter muscles. The curves were fit with biexponential functions. RESULTS: Increased signal intensity in the corpus callosum was evident 2-3 days after the first TET injection. At this time, a substantial slowly relaxing component appeared in the decay curves of the corpus callosum and, to a lesser extent, in the thalamus and hypothalamus. Changes in the rabbits' body weight, general physical condition, and neurologic state paralleled the growth and regression of the second, slowly relaxing component. CONCLUSION: The appearance and regression of a slowly decaying second component in the T2 decay curve is consistent with the formation and shrink-age of intracellular vesicles in the intramyelin sheaths of central white matter.

Animals↗

PubMed1995

The evolution of multiple sclerosis lesions on serial MR.

PURPOSE: To characterize temporal changes in signal intensity patterns of multiple sclerosis lesions on serial MR. METHODS: T1-, T2-, proton density-, and contrast-enhanced T1-weighted MR was performed on five patients with relapsing-remitting multiple sclerosis at least 22 times in the course of 1 year. RESULTS: Forty-three enhancing lesions and 1 new lesion that never showed enhancement were detected and followed for periods ranging from approximately 4 weeks to 1 year (total of 702 time points). At first detection the center of new lesions was brighter than the periphery (20 of 24 new lesions on proton density-weighted and 19 of 23 new lesions on contrast-enhanced images). On contrast-enhanced images, ring hyperintensity was predominant at time points later than 29 days. As lesions aged, a residual rim of "nonenhancing" hyperintensity often was noted on contrast-enhanced images. Some older lesions (> 1 year) showed similar appearance on unenhanced T1-weighted images. On proton density-weighted images ring hyperintensity was most frequent 2 to 4 months after lesion detection. The estimated average duration of gadopentetate dimeglumine enhancement was 1 to 2 months. CONCLUSIONS: A lesion evolution pattern relevant to MR was inferred. We believe that specific information about the histopathologic evolution of a lesion may be extracted not only from contrast-enhanced but also from nonenhanced serial MR. Assessment of drugs targeting specific phases of lesion evolution could benefit from quantitative pattern analysis of routine MR images.

Adult↗

PubMed1994

Longitudinal MRI in multiple sclerosis: correlation between disability and lesion burden.

We followed 18 multiple sclerosis patients clinically and with repeated brain MRIs with and without gadolinium for over 1 year. Clinical evaluations included scoring on the Kurtzke Expanded Disability Status Scale (EDSS) and the Ambulation Index (AI) scale. There was a significant correlation between the change in EDSS or AI and the change in number of lesions on MRI and between cumulative number of lesions on MRI and cumulative change in EDSS or AI. Our findings support the validity of MRI as a measure of clinical activity and potentially as an objective quantitative outcome measure for assessing response to therapy.

Adult↗

PubMed1993

MRI guided interstitial laser therapy in a rat malignant glioma model.

We have used MR monitoring to guide and evaluate the effects of the Nd:YAG interstitial laser on a well-characterized rat brain tumor model (C6). MRI was used to determine the tumor size, verify the location of the interstitial probe, and evaluate the size and location of the laser-induced lesion during and after treatment. During laser irradiation, an irreversible loss of signal intensity at the fiber tip and a reversible decrease in signal intensity around it were observed with MRI. None of the treatment protocols affected mean rat survival significantly. Although MRI-guided interstitial laser therapy appears to be safe and easy, it does not provide a curative treatment for spatially disseminated gliomas where a "target volume" cannot be adequately defined. Better results can be expected, especially in well-defined tumors, with improvements of both the imaging techniques and the laser treatment protocol.

Animals↗

PubMedDate not supplied

Routine quantitative analysis of brain and cerebrospinal fluid spaces with MR imaging.

A computerized system for processing spin-echo magnetic resonance (MR) imaging data was implemented to estimate whole brain (gray and white matter) and cerebrospinal fluid volumes and to display three-dimensional surface reconstructions of specified tissue classes. The techniques were evaluated by assessing the radiometric variability of MR volume data and by comparing automated and manual procedures for measuring tissue volumes. Results showed (a) the homogeneity of the MR data and (b) that automated techniques were consistently superior to manual techniques. Both techniques, however, were affected by the complexity of the structure, with simpler structures (eg, the intracranial cavity) showing less variability and better spatial correlation of segmentation results between raters. Moreover, the automated techniques were completed for whole brain in a fraction of the time required to complete the equivalent segmentation manually. Additional evaluations included interrater reliability and an evaluation that included longitudinal measurement, in which one subject was imaged sequentially 24 times, with reliability computed from data collected by three raters over 1 year. Results showed good reliability for the automated segmentation procedures.

Body Fluid Compartments↗