Bernard J. Dardzinski

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. Hum Brain Mapp, 2005.

Spatial variation in cartilage T2 of the knee

Technical limitations imposed by resolution and B1 homogeneity have thus far limited quantitative in vivo T2 mapping of cartilage to the patella. The purpose of this study is to develop T2 mapping of the femoral/tibial joint and assess regional variability of cartilage T2 in the knee. Quantitative in vivo T2 mapping of the knee was performed on 15 asymptomatic adults (age, 22–44) using a 3T MR scanner. There is a consistent pattern of spatial variation in cartilage T2 with longer values near the articular surface. The greatest variation occurs in the patella, where T2 increases from 45.3 ± 2.5 msec at a normalized distance of 0.33–67 ± 5.5 msec at a distance of 1.0. These results demonstrate feasibility of performing in vivo T2 mapping of femoral tibial cartilage. Except for the superficial 15% where T2 values are lower, the spatial variation in T2 of femoral and tibial cartilage is similar to patellar cartilage. J. Magn. Reson. Imaging 2001;14:50–55.

Simultaneous correction of ghost and geometric distortion artifacts in EPI using a multiecho reference scan

A computationally efficient technique is described for the simultaneous removal of ghosting and geometrical distortion artifacts in echo-planar imaging (EPI) utilizing a multiecho, gradient-echo reference scan. Nyquist ghosts occur in EPI reconstructions because odd and even lines of k-space are acquired with opposite polarity, and experimental imperfections such as gradient eddy currents, imperfect pulse sequence timing, B/sub 0/ field inhomogeneity, susceptibility, and chemical shift result in the even and odd lines of k-space being offset by different amounts relative to the true center of the acquisition window. Geometrical distortion occurs due to the limited bandwidth of the EPI images in the phase-encode direction. This distortion can be problematic when attempting to overlay an activation map from a functional magnetic resonance imaging experiment generated from EPI data on a high-resolution anatomical image. The method described here corrects for geometrical distortion related to B/sub 0/ inhomogeneity, gradient eddy currents, radio-frequency pulse frequency offset, and chemical shift effect. The algorithm for removing ghost artifacts utilizes phase information in two dimensions and is, thus, more robust than conventional one-dimensional methods. An additional reference scan is required which takes approximately 2 min for a matrix size of 64/spl times/64 and a repetition time of 2 s. Results from a water phantom and a human brain at 3 T demonstrate the effectiveness of the method for removing ghosts and geometric distortion artifacts.

MRI diffusion mapping of reversible and irreversible ischemic injury in focal brain ischemia

The reduction of the apparent diffusion coefficient (ADC) of water shortly after a focal ischemic insult is thought to reflect intracellular water accumulation (cytotoxic edema) related to high-energy metabolism failure and loss of ion homeostasis. We attempted to clarify whether varying ranges of ADC measurements in ischemic brain tissue can be used to differentiate between reversible and irreversible ischemic lesions before reperfusion in a temporary ischemia model. We induced 45 minutes of temporary ischemia in 12 rats using the middle cerebral artery suture occlusion method. Regional changes of ADC values were serially measured in seven regions of interest in each hemisphere and evaluated by ΔADC, defined as the difference between ADC value in an ischemic region and that in a contralateral homologous region. We acquired dynamic contrast-enhanced perfusion images 2 minutes before and after reperfusion to document reduced perfusion and its restoration. We confirmed the infarct area by 2,3,5-triphenyltetrazolium chloride staining 24 hours after occlusion and correlated this with the MRI studies. Recovery of initially reduced ADC values occurred only in ischemic regions where ΔADC values were not below −0.25 × 10−5 cm2/sec. Although the extent of infarction at postmortem examination varied in regions with moderately decreased prereperfusion ADC values, more than 70% of regions of interest with slight declines of prereperfusion ADC values exhibited no infarction. ADC values progressively decreased after reperfusion in regions that initially had severely decreased prereperfusion ADC values, and postmortem examination always demonstrated infarction in such regions. These results suggest that measurement of ΔADC can provide information that will enable the clinician to discriminate between irreversible and potentially reversible ischemic regions before reperfusion is performed.

Developmental differences in white matter architecture between boys and girls

Previous studies have found developmental differences between males and females in brain structure. During childhood and adolescence, relative white matter volume increases faster in boys than in girls. Sex differences in the development of white matter microstructure were investigated in a cohort of normal children ages 5–18 in a cross‐sectional diffusion tensor imaging (DTI) study. Greater fractional anisotropy (FA) in boys was shown in associative white matter regions (including the frontal lobes), while greater FA in girls was shown in the splenium of the corpus callosum. Greater mean diffusivity (MD) in boys was shown in the corticospinal tract and in frontal white matter in the right hemisphere; greater MD in girls was shown in occipito‐parietal regions and the most superior aspect of the corticospinal tract in the right hemisphere. Significant sex–age interactions on FA and MD were also shown. Girls displayed a greater rate of fiber density increase with age when compared with boys in associative regions (reflected in MD values). However, girls displayed a trend toward increased organization with age (reflected in FA values) only in the right hemisphere, while boys displayed this trend only in the left hemisphere. These results indicate differing developmental trajectories in white matter for boys and girls and the importance of taking sex into account in developmental DTI studies. The results also may have implications for the study of the relationship of brain architecture with intelligence. Hum Brain Mapp, 2008.

Measures of Molecular Composition and Structure in Osteoarthritis

Osteoarthritis involves ongoing degradative and healing processes that occur at the molecular level in multiple tissues in the joint in response to a number of biochemical and mechanical factors. Understanding these dynamic processes before they affect the structural aspects of the joint motivates the need for metrics to better visualize the compositional and structural molecular aspects of the tissues in vivo. As reviewed here, most of the work to date in this regard has been focused on magnetic resonance imaging approaches for interrogating molecular features of cartilage, including T2 mapping, T1rho mapping, delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), and sodium imaging. Specific examples illustrate new opportunities and insights emerging from these methods.

Multislice diffusion mapping for 3-D evolution of cerebral ischemia in a rat stroke model

Article abstract-Diffusion-weighted magnetic resonance imaging (DWI) can quantitatively demonstrate cerebral ischemia within minutes after the onset of ischemia. The use of a DWI echo-planar multislice technique in this study and the mapping of the apparent diffusion coefficient (ADC) of water, a reliable indicator of ischemic regions, allow for the detection of the three-dimensional (3-D) evolution of ischemia in a rat stroke model. We evaluated 13 time points from 5 to 180 minutes after occlusion of the middle cerebral artery (MCA) and monitored the 3-D spread of ischemia. Within 5 minutes after the onset of ischemia, regions with reduced ADC values occurred. The core of the lesion, with the lowest absolute ADC values, first appeared in the lateral caudoputamen and frontoparietal cortex, then spread to adjacent areas. The volume of ischemic tissue was 224 +\- 48.5 mm3 (mean +\- SEM) after 180 minutes, ranging from 92 to 320 mm3, and this correlated well with the corrected infarct volume at postmortem (194 +\- 23.1 mm3, r = 0.72, p < 0.05). This experiment demonstrated that 3-D multislice diffusion mapping can detect ischemic regions noninvasively 5 minutes after MCA occlusion and follow the development of ischemia. The distribution of changes in absolute ADC values within the ischemic region can be followed over time, giving important information about the evolution of focal ischemia. NEUROLOGY 1995;45: 172-177

MR imaging of murine arthritis using ultrasmall superparamagnetic iron oxide particles

The objective of this work was to determine the ability of magnetic resonance (MR) imaging with ultrasmall superparamagnetic iron oxide (USPIO) particles to provide quantitative measures of inflammation in autoimmune arthritis. Mice were injected intravenously or intra-articularly with USPIO followed by magnetic resonance and histological assessment of the knee joint. Comparisons were made between MR microimages and histology in naïve mice and mice with collagen-induced arthritis.Following intravenous administration, accumulation of USPIO was observed in the popliteal lymph nodes, but not the joint. Administration of USPIO intra-articularly resulted in signal loss in the joint. The MR signal intensity could be quantified and correlated with iron staining in the synovial lining. A marked increase in USPIO uptake and a corresponding decrease in signal intensity were observed in arthritic, compared to naïve mice. Areas of focal signal loss corresponded to foci of iron staining by histology. These studies may provide a basis for the clinical application of USPIO in arthritis for assessing disease severity and monitoring response to therapy.

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

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.

Modest hypothermia preserves cerebral energy metabolism during hypoxia-ischemia and correlates with brain damage : A 31P nuclear magnetic resonance study in unanesthetized neonatal rats

Recent studies have shown that mild to moderate (modest) hypothermia decreases the damage resulting from hypoxic-ischemic insult (HI) in the immature rat. To determine whether suppression of oxidative metabolism during HI is central to the mechanism of neuroprotection, 31P nuclear magnetic resonance (NMR) spectroscopy was used to measure high energy metabolites in 7-d postnatal rats under conditions of modest hypothermia during the HI. The rats underwent unilateral common carotid artery ligation followed by exposure to hypoxia in 8% oxygen for 3 h. Environmental temperature was decreased by 3 or 6 °C from the control temperature, 37 °C, which reliably produces hemispheric damage in over 90% of pups. The metabolite parameters and tissue swelling (edema) at 42 h recovery varied very significantly with the three temperatures. Tissue swelling was 26.9, 5.3, and 0.3% at 37, 34, and 31 °C, respectively. Core temperature and swelling were also measured, with similar results, in parallel experiments in glass jars. Multislice magnetic resonance imaging, histology, and triphenyltetrazolium chloride staining confirmed the fairly uniform damage, confined to the hemisphere ipsilateral to the ligation. The NMR metabolite levels were integrated over the last 2.0 h out of 3.0 h of HI, and were normalized to their baseline for all surviving animals (n = 25). ATP was 47.9, 69.0, and 83.0% of normal, whereas the estimator of phosphorylation potential (phosphocreatinine/inorganic phosphorus) was 16.9, 27.8, and 42.6% of normal at 37, 34, and 31 °C, respectively. There was a significant correlation of both phosphocreatinine/inorganic phosphorus (p < 0.0001) and ATP levels (p < 0.0001) with brain swelling. Abnormal brain swelling and thus damage can be reliably predicted from a threshold of these metabolite levels (p < 0.0001). Thus for all three temperatures, a large change in integrated high energy metabolism during HI is a prerequisite for brain damage. With a moderate hypothermia change of 6 °C, where there is an insufficient change in metabolites, there is no subsequent HI brain damage. In general, treatment for HI in our 7-d-old rat model should be aimed at preserving energy metabolism.