PubMed Health⌕ Search

Biomedical subjects

Bernard J Dardzinski

Publications and source records attributed to Bernard J Dardzinski.

At least 19 recordsLinked to original sources

Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy.

Hypoxia is a critical factor for cell death or survival in ischemic stroke, but the pathological consequences of combined ischemia-hypoxia are not fully understood. Here we examine this issue using a modified Levine/Vannucci procedure in adult mice that consists of unilateral common carotid artery occlusion and hypoxia with tightly regulated body temperature. At the cellular level, ischemia-hypoxia produced proinflammatory cytokines and simultaneously activated both prosurvival (eg, synthesis of heat shock 70 protein, phosphorylation of ERK and AKT) and proapoptosis signaling pathways (eg, release of cytochrome c and AIF from mitochondria, cleavage of caspase-9 and -8). However, caspase-3 was not activated, and very few cells completed the apoptosis process. Instead, many damaged neurons showed features of autophagic/lysosomal cell death. At the tissue level, ischemia-hypoxia caused persistent cerebral perfusion deficits even after release of the carotid artery occlusion. These changes were associated with both platelet deposition and fibrin accumulation within the cerebral circulation and would be expected to contribute to infarction. Complementary studies in fibrinogen-deficient mice revealed that the absence of fibrin and/or secondary fibrin-mediated inflammatory processes significantly attenuated brain damage. Together, these results suggest that ischemia-hypoxia is a powerful stimulus for spontaneous coagulation leading to reperfusion deficits and autophagic/lysosomal cell death in brain.

Animals↗

Cognitive functions correlate with white matter architecture in a normal pediatric population: a diffusion tensor MRI study.

A possible relationship between cognitive abilities and white matter structure as assessed by magnetic resonance diffusion tensor imaging (DTI) was investigated in the pediatric population. DTI was performed on 47 normal children ages 5-18. Using a voxelwise analysis technique, the fractional anisotropy (FA) and mean diffusivity (MD) were tested for significant correlations with Wechsler full-scale IQ scores, with subject age and gender used as covariates. Regions displaying significant positive correlations of IQ scores with FA were found bilaterally in white matter association areas, including frontal and occipito-parietal areas. No regions were found exhibiting correlations of IQ with MD except for one frontal area significantly overlapping a region containing a significant correlation with FA. The positive direction of the correlation with FA is the same as that found previously with age, and indicates a positive relationship between fiber organization and/or density with cognitive function. The results are consistent with the hypothesis that regionally specific increased fiber organization is a mechanism responsible for the normal development of white matter tracts.

Adolescent↗

Quantifying dynamic contrast-enhanced MRI of the knee in children with juvenile rheumatoid arthritis using an arterial input function (AIF) extracted from popliteal artery enhancement, and the effect of the choice of the AIF on the kinetic parameters.

Quantification of dynamic contrast-enhanced (DCE) MRI based on pharmacokinetic modeling requires specification of the arterial input function (AIF). A full representation of the plasma concentration data, including the initial rise and decay parts, considering the delay and dispersion of the bolus contrast is important. This work deals with modeling of DCE-MRI data from the knees of children with a history of juvenile rheumatoid arthritis (JRA) by using an AIF extracted from the signal enhancement data from the nearby popliteal artery. Three models for the AIFs were considered: a triexponential (AIF1), a gamma-variate plus a biexponential (AIF2), and a biexponential (AIF3). The pharmacokinetic parameters obtained from the model were Ktrans', kep, and V'p. The results from AIF1 and AIF2 showed no statistically significant difference. However, some statistically significant differences were seen with AIF3, particularly for parameters Ktrans' and V'p in the synovium (SNVM). These results suggest the importance of obtaining an appropriate AIF representation in pharmacokinetic modeling of JRA. Specifically, the initial rising part of the AIF should be incorporated for optimal pharmacokinetic modeling results. The pharmacokinetic parameters (mean+/-SD) derived from AIF1, using the average plasma concentration data, were as follows: SNVM Ktrans'(min-1)=0.52+/-0.34, kep(min-1)=0.71+/-0.39, and V'p=0.33+/-0.16, and for the distal femoral physis (DFP) Ktrans'(min-1)=1.83+/-1.78, kep(min-1)=2.65+/-1.80, and V'p=0.46+/-0.31. The pharmacokinetic parameters in the SNVM may be useful for investigating activity and therapeutic efficacy in studies of JRA. Longitudinal studies are necessary to find or demonstrate the parameter that is more sensitive to disease activity.

Adolescent↗

MRI of fat distribution in a mouse model of lysosomal acid lipase deficiency.

OBJECTIVE: We assessed the use of MRI in the evaluation of abdominal fat distribution in a lysosomal acid lipase (LAL)-deficient mouse model. MATERIALS AND METHODS: LAL-deficient mice are born with a normal fat distribution but over time deplete the fat stores in the subcutaneous and retroperitoneal tissues and accumulate fat in the liver, spleen, and bowel. Four MRI studies of LAL-deficient mice and control mice were obtained with 3-T T1-weighted spin-echo images and volume segmentation processing to create parameters for the study of fat distribution: intraabdominal adipose tissue-subcutaneous adipose tissue (IAT/SAT) ratio, liver volume, reproductive fat, and retroperitoneal fat. MRI adiposity parameters in LAL-deficient mice were compared with those in control mice. Adiposity volumes calculated on MRI were compared with those calculated at autopsy. RESULTS: Statistically significant differences were found between LAL-deficient and control mice for IAT/SAT ratio (p=0.0336), liver volume (p=0.0336), and reproductive fat (p=0.0336), and a statistically significant trend was found for retroperitoneal fat (p=0.0514). No statistically significant difference was found between adiposity volumes calculated on MRI and adiposity volumes found at autopsy (all p >0.2). CONCLUSION: Use of an in vivo model showed MRI techniques to be accurate in predicting visceral adiposity. LAL-deficient mice provided a unique model showing a pattern of adipose distribution that is markedly different from that in control mice, and MRI may provide a means of evaluating therapeutic interventions sequentially.

Abdomen↗

Quantitative magnetic resonance imaging of the hands and wrists of children with juvenile rheumatoid arthritis.

OBJECTIVE: To assess feasibility of measuring synovial volume in the hand and wrist in patients with polyarticular course juvenile rheumatoid arthritis (JRA) by magnetic resonance imaging (MRI). As well, to compare clinical variables with synovial volume calculated from MRI in patients receiving disease modifying or biologic therapy. METHODS: Ten patients with polyarticular course JRA starting methotrexate (n = 3) or etanercept (n = 7) therapy had MRI with intravenous contrast performed of one hand and wrist at baseline and after 6 weeks and 3 months of pharmacotherapy. Synovial volume was determined for the entire hand and wrist and also for regions. Patients were assessed clinically by the core set of outcome variables for JRA and total hand swelling score, and assessed for clinical improvement based upon change in these variables. RESULTS: Increased synovial volume was observed at entry by MRI in all patients (range 2.4-12.5 cc, median 3.7 cc). Correlation of total synovial volume from MRI with total hand swelling score at each timepoint was good (r = 0.52-0.68). Correlation with other clinical variables was not consistently strong. Patients who improved clinically did not differ from patients who did not improve clinically with respect to change in synovial volume. CONCLUSION: Determining synovial volume in the hand and wrist in patients with JRA by MRI is feasible and correlates with total hand swelling assessed on physical examination. Inconsistent or poor correlation with other clinical variables and the clinical definition of improvement requires further study.

Adolescent↗

Change in knee cartilage T2 at MR imaging after running: a feasibility study.

All participants provided informed consent to participate in this study, which was approved by the institutional review board of Milton S. Hershey Medical Center. The purpose of the study was to determine the feasibility of cartilage T2 mapping in the evaluation of response of femoral and tibial cartilage to running exercise. Quantitative magnetic resonance (MR) T2 maps of weight-bearing femoral and tibial articular cartilage were obtained in seven young healthy men before and immediately after 30 minutes of running by using a 3.0-T MR imager. There was no statistically significant change in T2 profiles of tibial cartilage. There was a statistically significant decrease in T2 of the superficial 40% of weight-bearing femoral cartilage after exercise. These in vivo observations agree well with published ex vivo results and support the hypothesis that cartilage compression results in greater anisotropy of superficial collagen fibers.

Adult↗

Interphalangeal joint cartilage: high-spatial-resolution in vivo MR T2 mapping--a feasibility study.

The purpose of this study was to evaluate feasibility of magnetic resonance (MR) T2 mapping of the proximal interphalangeal joint of the index finger. Cartilage T2 maps with an in-plane resolution of 39 microm were obtained from five asymptomatic subjects-four men and one woman, aged 24-45 years-by using a 3.0-T MR imager. Image acquisition time was 9.6 minutes. All cartilage T2 maps demonstrated spatial variation similar to that reported previously for knee cartilage, with T2 values increasing toward the articular surface. These results demonstrate the feasibility of acquiring cartilage T2 maps of small joints in the hand. Application of T2 mapping techniques to non-weight-bearing joints may provide a means for differentiation of local biomechanical and systemic factors that can affect cartilage T2 values.

Adult↗

Magnetic resonance imaging evaluation of the effects of juvenile rheumatoid arthritis on distal femoral weight-bearing cartilage.

OBJECTIVE: To examine magnetic resonance imaging-derived T2 relaxation times in the weight-bearing cartilage of the distal femur in healthy children and in children with juvenile rheumatoid arthritis (JRA). METHODS: T2 relaxation time maps were created for 39 girls (ages 4.9-10.9 years), 21 of whom were considered healthy and 18 of whom had JRA. The spatial distribution of T2 relaxation times for the distal femoral weight-bearing cartilage (including epiphyseal and articular cartilage) was mapped for each group as a whole. Average data sets for each group were then compared using paired t-tests to detect differences between the 2 populations. RESULTS: The spatial distribution of T2 relaxation time values was nearly identical in the 2 groups, with a concave curve that was highest near the subchondral bone and articular surfaces. The average T2 relaxation times were significantly higher in the girls with JRA than in the group of healthy girls (P < 0.05). CONCLUSION: The finding of an increased average T2 relaxation time in the children with JRA suggests that T2 relaxation time maps may reflect cartilage microstructure differences that occur in JRA. T2 relaxation time mapping may allow for early detection of cartilage changes and provide an objective, quantitative method of monitoring disease progression, with the long-term potential to guide therapy.

Adult↗

Age dependency of cartilage magnetic resonance imaging T2 relaxation times in asymptomatic women.

OBJECTIVE: Because the magnetic resonance imaging (MRI) transverse relaxation time (T2) of cartilage is sensitive to organization of collagen fibers in the cartilage, it may be a noninvasive image marker for senescent changes in cartilage collagen and early cartilage degeneration. The purpose of this study was to determine age-dependent differences in cartilage T2 values in healthy asymptomatic women. METHODS: Quantitative T2 maps of patellar cartilage from 30 asymptomatic women ages 22-86 years were obtained using a 3.0T MRI scanner. The study population was stratified by age into 4 cohorts: 18-30, 31-45, 46-65, and 66-86 years. Spatial differences in cartilage T2 were determined as a function of normalized distance from bone. Older groups were compared with the 18-30-year-old group to determine the effects of age on cartilage T2 values. Regions were considered statistically significantly different if the mean T2 values between groups differed at P < 0.05. RESULTS: Mean cartilage T2 profiles were nearly identical for the 2 youngest cohorts. Compared with the 18-30-year-old group, T2 values were statistically significantly longer in the superficial 40% of cartilage in the 46-65-year-old group and over the entire cartilage thickness in the 66-86-year-old group. CONCLUSION: The location of T2 elevations in women over the age of 45 years is consistent with the theory that senescent changes of cartilage collagen begin near the articular surface and progress to the deeper cartilage with advancing age.

Adolescent↗

Effect of gender on in vivo cartilage magnetic resonance imaging T2 mapping.

PURPOSE: To determine if gender is a significant variable for in vivo magnetic resonance imaging (MRI) T2-mapping of knee articular cartilage in young asymptomatic volunteers. MATERIALS AND METHODS: Cartilage MRI T2 mapping was performed in a young healthy population consisting of seven male and 10 female volunteers, 22 to 29 years of age. High-resolution in vivo T2 maps were obtained of patellar, tibial, and weight-bearing femoral articular cartilage. Spatial dependency of cartilage T2 between groups was evaluated through a comparison of cartilage T2 as a function of normalized distance from bone. RESULTS: Bulk cartilage T2 values were similar at all three anatomic sites, and between male and female volunteers. All volunteers demonstrated similar spatial variation in cartilage MRI T2 values, with a minimum located in the radial zone and increasing T2 values toward the articular surface. There was no difference in spatial dependency of cartilage T2 between males and females. CONCLUSION: In young, healthy volunteers, the magnitude and spatial dependency of cartilage T2 does not differ with gender.

Adult↗

Quantification of dynamic contrast-enhanced MR imaging of the knee in children with juvenile rheumatoid arthritis based on pharmacokinetic modeling.

Improved management of arthritis requires a reliable, quantifiable, noninvasive method to monitor the degree of inflammation and therapeutic response during the early phase of the disease. For this purpose, the uptake of Gd-DTPA in the distal femoral physis and synovium in children with juvenile rheumatoid arthritis (JRA) was evaluated with a two-compartment pharmacokinetic model and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Employing a two-compartment pharmacokinetic model, the theoretical signal enhancement from Gd-DTPA enhanced dynamic 3D gradient-recalled echo (GRE) images was shown to have a simple linear relationship with tissue concentration independent of flip angle. The signal-enhancement patterns for each individual knee were found to be characterized by three pharmacokinetic parameters: k(ep) (min(-1)), the rate constant; k(el) (min(-1)), the elimination rate constant; and E(R) (min(-1)), the initial enhancement rate, which is proportional to the transfer constant K(trans) (min(-1)). Characteristic patterns were observed in the image signal intensity-time course. The initial enhancement rate, E(R), in regions of interest (ROIs) was found to have a wide range of variation: 5 to 38 min(-1) over the distal femoral physis and 1 to 10 min(-1) in the synovium. The E(R) of the synovium was correlated with the E(R) of the distal femoral physis (P<.05). In addition, the E(R) of the synovium was correlated to the clinical outcome measures of knee swelling. Further investigation is needed to determine whether wide variations in the pharmacokinetic parameters reflect the degree of disease activity, and whether there are changes in response to therapy. This method can also be applied in adults with rheumatoid arthritis (RA) and other disorders where T(1)-weighted contrast is used (breast cancer, brain tumors).

Adolescent↗

Cartilage MRI T2 relaxation time mapping: overview and applications.

The sensitivity of magnetic resonance imaging to biochemical and biophysical changes in the extracellular matrix of articular cartilage give it the potential to noninvasively detect the earliest changes of cartilage damage. The transverse relaxation time (T2) of cartilage has been shown to be a sensitive parameter for evaluation of early degeneration in articular cartilage, particularly changes in water and collagen content and tissue anisotropy. Although initial application has been in microimaging of small cartilage explants, in vivo techniques have been developed for cartilage T2 mapping of human joints. In addition to potential application in development of new pharmaceuticals and surgical techniques for preserving cartilage, in vivo cartilage T2 mapping can improve understanding of arthritis, cartilage aging, and response of cartilage to exercise.

Aging↗

Obstructive sleep apnea: MR imaging volume segmentation analysis.

PURPOSE: To retrospectively determine airway wall motion with volume segmentation of transverse cine magnetic resonance (MR) images in children with obstructive sleep apnea (OSA). MATERIALS AND METHODS: Transverse fast gradient-echo cine MR images of the hypopharynx were obtained at 1.5 T in 31 children with OSA (eight girls, 23 boys; mean age, 11.3 years) and 21 children free of airway symptoms who underwent MR imaging for other clinical indications (11 girls, 10 boys; mean age, 3.5 years). Volume segmentation with a k-means clustering algorithm was applied to transverse cine MR images to quantify airway volumes at each time. Airway wall motion for each child was described with standard deviation and range. Coefficient of variance and normalized range, which are independent of airway size, were used to compare groups (Kruskal-Wallis test). RESULTS: Plots of airway volume over time demonstrated large fluctuations during respiration in children with OSA and minimal fluctuations in controls; findings were consistent with airway distention and airway collapse in OSA. Average airway transverse volume was larger in the group with OSA than in the control group (OSA group, 2.52 mL; control group, 0.936 mL; P <.001). Mean standard deviation (OSA group, 0.840 mL; control group, 0.17 mL; P <.001) and mean range of airway cross section (OSA group, 3.552 mL; control group, 0.864 mL; P <.001) were larger in the group with OSA. Coefficient of variance (OSA group, 0.32; control group, 0.17; P <.001) and normalized range (OSA group, 1.42; control group, 0.96; P <.001) indicate statistically significant difference in airway dynamics in children with OSA. CONCLUSION: Volume segmentation of transverse cine MR images of the hypopharynx aids in quantification of increased airway wall motion in children with OSA. Transverse MR imaging demonstrates both airway distention and collapse in children with OSA.

Child↗

Using a phantom to compare MR techniques for determining the ratio of intraabdominal to subcutaneous adipose tissue.

OBJECTIVE: Patients who have a greater distribution of intraabdominal adipose tissue as compared with subcutaneous adipose tissue and an increased ratio of intraabdominal adipose tissue to subcutaneous adipose tissue are at greater risk for developing cardiovascular disease and type 2 diabetes mellitus. In previous MR investigations, researchers have used conventional T1-weighted spin-echo images to determine the ratio of intraabdominal adipose tissue to subcutaneous adipose tissue. However, no investigation, to our knowledge, has been performed to determine the accuracy of using different MR sequences to estimate adipose distribution. The purpose of our investigation was to compare MR imaging and segmentation techniques in calculating the ratio of intraabdominal to subcutaneous adipose tissue using an adiposity phantom. MATERIALS AND METHODS: A phantom was created to simulate the distribution of subcutaneous and intraabdominal fat (with known volumes). Axial MR images were obtained twice through the phantom using a 5-mm slice thickness and zero gap for the following T1-weighted sequences: spin-echo, fast Dixon, and three-dimensional (3D) spoiled gradient-echo. An in-house computer software program was then used to segment the volumes of fat and calculate the volume of intraabdominal adipose tissue and subcutaneous adipose tissue and the ratio of intraabdominal to subcutaneous adipose tissue. Each imaging data set was segmented three times, so six sets of data were yielded for each imaging technique. The percentage predicted of the true volume was calculated for each MR imaging technique for each fat variable. The mean percentages for each variable were then compared using one-factor analysis of variance to determine whether differences exist among the three MR techniques. RESULTS: The three MR imaging techniques had statistically significant different means for the predicted true volume of two variables: volume of subcutaneous adipose tissue (p < 0.001) and volume of intraabdominal adipose tissue (p = 0.0426). Estimates based on fast Dixon images were closest to the true volumes for all the variables. All MR imaging techniques performed similarly in estimating the ratio of intraabdominal adipose tissue to subcutaneous adipose tissue (p = 0.9117). The acquisition time for the 3D spoiled gradient-echo images was 10-22 times faster than for the other sequences. CONCLUSION: Conventional T1-weighted spin-echo MR imaging, the current sequence used in practice for measuring visceral adiposity, may not be the optimal MR sequence for this purpose. We found that the T1-weighted fast Dixon sequence was the most accurate at estimating all fat volumes. The T1-weighted 3D spoiled gradient-echo sequence generated similar ratios of intraabdominal to subcutaneous adipose tissue in a fraction of the acquisition time.

Abdominal Cavity↗

Automatic gradient preemphasis adjustment: a 15-minute journey to improved diffusion-weighted echo-planar imaging.

Image distortion caused by gradient eddy currents is a major problem in the use of diffusion tensor imaging (DTI), as using the uncorrected images for calculation of apparent diffusion coefficient (ADC) and diffusion anisotropy will result in areas of artificially increased anisotropy and ADC at the edge of the images, as well as decreased spatial resolution and accuracy in ADC computations overall. This distortion may be substantially reduced by careful adjustment of the gradient preemphasis unit. A completely automatic method of adjusting the preemphasis unit is proposed which finds the optimal settings for all three gradient directions in approximately 15 min by estimating the magnitudes of the eddy currents at various delay times after a test gradient. The pixel shifts in a 64 x 128 echo-planar diffusion-weighted image with a diffusion gradient strength of 30 mT/m were reduced to less than 0.2.

Calibration↗

Correlation of white matter diffusivity and anisotropy with age during childhood and adolescence: a cross-sectional diffusion-tensor MR imaging study.

PURPOSE: To evaluate differences in white matter diffusion properties as a function of age in healthy children and adolescents. MATERIALS AND METHODS: Echo-planar diffusion-tensor magnetic resonance (MR) imaging was performed in 33 healthy subjects aged 5-18 years who were recruited from a functional imaging study of normal language development. Results of neurologic, psychologic, and structural MR imaging examinations were within the normal range for all subjects. The trace of the apparent diffusion coefficient and fractional anisotropy in white matter were correlated as a function of age by using Spearman rank correlation. RESULTS: Statistically significant negative correlation of the trace of the apparent diffusion coefficient with age was found throughout the white matter. Significant positive correlation of fractional anisotropy with age was found in the internal capsule, corticospinal tract, left arcuate fasciculus, and right inferior longitudinal fasciculus. CONCLUSION: Diffusion-tensor MR imaging results indicate that white matter maturation assessed at different ages involves increases in both white matter density and organization during childhood and adolescence. The trace of the apparent diffusion coefficient and fractional anisotropy may reflect different physiologic processes in healthy children and adolescents.

Adolescent↗

Posterior distal femoral and proximal tibial metaphyseal stripes at MR imaging in children and young adults.

PURPOSE: To determine the frequency and distribution of the hyperintense stripe seen along the posterior surface of distal femoral and proximal tibial metaphyses at magnetic resonance (MR) imaging. MATERIALS AND METHODS: One hundred forty-two MR imaging studies obtained in 139 children and young adults were reviewed. The authors recorded the presence and distribution of posterior distal femoral and proximal tibial metaphyseal stripes. Presence of stripe was correlated with patient age and sex and with patency of the adjacent physis. Fifty-nine studies of adults were reviewed similarly. Two-way analysis of variance was performed to compare mean patient age for sex among four different categories that were based on stripe presence and physeal patency. Orthogonal contrasts were used to determine whether a linear trend across the categories existed. In one cadaveric femur, imaging and histologic analysis were performed. RESULTS: A metaphyseal stripe was seen in all patients with a completely or partially open physis (110 femora, 102 tibiae) and in 56 femora and 60 tibiae in the patients with fused physes. Thirty-five femora and 35 tibiae showed no stripe; all patients were skeletally mature. Correlations between metaphyseal stripe visualization and physeal patency were significant (P <.001). Differences in mean patient age among the four categories were significant for both (femoral and tibial) locations (P <.001), and a linear trend with age (P <.001) was demonstrated. This linear trend was also observed in both sexes (P <.001). Histologic analysis revealed highly vascular loose fibrous tissue. CONCLUSION: A posterior metaphyseal stripe is seen at MR imaging of the skeletally immature knee and likely reflects normal bone growth.

Adolescent↗