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Biomedical subjects

Robert V Mulkern

Publications and source records attributed to Robert V Mulkern.

At least 19 recordsLinked to original sources
PubMed2005

PSF-choice: a novel MRI method for shaping point-spread functions in phase-encoding dimensions.

An imaging method to obtain arbitrary point-spread functions (PSFs) in phase-encoding dimensions is described. This method, called PSF-Choice, is particularly relevant for applications, such as spectroscopic imaging, in which only a very few phase encodes are acquired and ringing artifact can be a serious problem. PSF-Choice uses partial 2D RF excitations to produce aliased excitations that are encoded using standard phase-encoding gradients. Theoretically, the PSF of the reconstructed result depends only on the RF excitation profile. Simulations demonstrate that a Gaussian-like PSF can be achieved, eliminating the side lobes that are associated with ringing artifact. It is further shown that neither the spatial resolution (as represented by the width of the PSF) nor the signal-to-noise ratio (SNR) of the method is adversely affected when compared to standard phase encoding. In the sense that the same number of encodes are required as with standard phase encoding, temporal resolution is also maintained. Phantom experiments demonstrate the initial feasibility of the method to eliminate ringing artifact.

Algorithms↗
PubMed2005

Biexponential parameterization of diffusion and T2 relaxation decay curves in a rat muscle edema model: decay curve components and water compartments.

Quantitative T2 relaxation and diffusion imaging studies of a rat muscle edema model were performed in order to determine the effects of intra- and extracellular water compartmentation on the respective decay curves. The right hind paw of rats was injected with a carrageenan solution to generate edematous muscle. A Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence was used to acquire T2 relaxation decay curves from both paws. A line scan diffusion imaging (LSDI) sequence was then used to acquire diffusion decay curves from the same paws over a wide b-factor range. Measurements were made from both edematous muscle (EM) and control muscle (CM). The EM and CM T2 relaxation decay curves were best fit with biexponential functions. The fraction of the fast T2 component dropped dramatically from approximately 0.95 in CM to 0.45 in EM, consistent with a water compartmentation model in which the fast and slow T2 components reflect intra- and extracellular water, respectively. Both CM and EM diffusion decay curves required biexponential fitting functions, and the diffusion coefficients of the fast and slow components were substantially larger in EM than CM. The fraction of the fast diffusion component, however, was not radically altered between CM and EM conditions (0.84 versus 0.89 for CM versus EM). Assuming a model in which intra- and extracellular water compartments are responsible for the fast and slow T2-decay components and for the slow and fast diffusion decay components, respectively, leads to fractional sizes of the diffusion components that are not supported by experiment. We conclude that intra- and extracellular water compartmentation is a reasonable interpretation for the two T2-decay components in both CM and EM but that other factors, such as restricted diffusion and/or alternate forms of water compartmentation like surface versus volume water, most probably have profound influences on the precise shapes of the diffusion decay curves, a complete understanding of which will require significant theoretical work.

Animals↗
PubMed2005

Magnetization transfer studies of the fast and slow tissue water diffusion components in the human brain.

Magnetization transfer (MT) properties of the fast and slow diffusion components recently observed in the human brain were assessed experimentally. One set of experiments, performed at 1.5 T in healthy volunteers, was designed to determine whether the amplitudes of fast and slow diffusion components, differentiated on the basis of biexponential fits to signal decays over a wide range of b-factors, demonstrated a different or similar magnetization transfer ratio (MTR). Another set of experiments, performed at 3 T in healthy volunteers, was designed to determine whether MTRs differed when measured from high signal-to-noise images acquired with b-factor weightings of 350 vs 3500 s/mm2. The 3 T studies included measurements of MTR as a function of off-resonance frequency for the MT pulse at both low and high b-factors. The primary conclusion drawn from all the studies is that there appears to be no significant difference between the magnetization transfer properties of the fast and slow tissue water diffusion components. The conclusions do not lend support to a direct interpretation of the 'components' of the biexponential diffusion decay in terms of the 'compartments' associated with intra- and extracellular water.

Adult↗
PubMed2005

The route of lipid administration affects parenteral nutrition-induced hepatic steatosis in a mouse model.

BACKGROUND: The etiology of parenteral nutrition (PN)-associated hepatic injury remains unresolved. Recent studies have suggested that the intravenous (IV) lipid emulsion administered with PN may contribute to PN-associated hepatic injury. We therefore examined whether the route of lipid administration would affect the development of PN-associated liver injury in a previously established animal model of PN-induced hepatic steatosis. METHODS: Mice were fed ad libitum PN solution as their only nutritional source for 19 days with lipid supplementation by either the enteral or the IV route. Control mice received chow alone, and a final group received enteral PN solution without lipid supplementation. RESULTS: All mice gained equivalent weight during the study. Mice receiving PN alone or PN with IV lipid developed severe histologic liver damage that was not seen in control mice or in mice receiving PN with enteral lipid. Liver fat content as measured by magnetic resonance spectroscopy was significantly lower in the control and enteral lipid groups when compared with mice receiving PN alone or with IV lipid. Mice receiving enteral lipid had significantly lower levels of serum aspartate aminotransferase and alanine aminotransferase compared with animals receiving PN alone. CONCLUSIONS: These data provide preliminary evidence that lipid administered through the enteral route protects against PN-associated hepatic injury in an animal model.

Animals↗
PubMed2005

On the strong field dependence and nonlinear response to gadolinium contrast agent of proton transverse relaxation rates in dairy cream.

Dairy cream, as a suspension of lipid droplets in water, is a potentially useful magnetic resonance imaging (MRI) phantom material and an interesting material for studying fundamental relaxation mechanisms. Here we report a strong increase in the transverse relaxation rates with field strength for both the water and lipid protons in dairy cream. Also, studies at 4.7 T reveal a nonlinear response of transverse relaxation rates with increasing concentration of a common gadolinium (Gd)-based contrast agent, including an initial decrease of water relaxation rates as measured with Hahn spin echoes at the lower Gd concentrations. The results are treated within the framework of a model in which the magnetic susceptibility difference between the lipid droplets and the aqueous phase plays the prominent role for transverse relaxation. Second-order polynomial fits of the water proton transverse relaxation rate dependence on field strength and on Gd concentration at 4.7 T provided experimental parameters from which model parameters are extracted and compared with expectations available from the literature.

Contrast Media↗
PubMed2004

Biexponential diffusion tensor analysis of human brain diffusion data.

Several studies have shown that in tissues over an extended range of b-factors, the signal decay deviates significantly from the basic monoexponential model. The true nature of this departure has to date not been identified. For the current study, line scan diffusion images of brain suitable for biexponential diffusion tensor analysis were acquired in normal subjects on a clinical MR system. For each of six noncollinear directions, 32 images with b-factors ranging from 5 to 5000 s/mm2 were collected. Biexponential fits yielded parameter maps for a fast and a slow diffusion component. A subset of the diffusion data, consisting of the images obtained at the conventional range of b-factors between 5 and 972 s/mm2, was used for monoexponential diffusion tensor analysis. Fractional anisotropy (FA) of the fast-diffusion component and the monoexponential fit exhibited no significant difference. FA of the slow-diffusion biexponential component was significantly higher, particularly in areas of lower fiber density. The principal diffusion directions for the two biexponential components and the monoexponential solution were largely the same and in agreement with known fiber tracts. The second and third diffusion eigenvector directions also appeared to be aligned, but they exhibited significant deviations in localized areas.

Adult↗
PubMed2004

Perfusion MRI of U87 brain tumors in a mouse model.

Continuous arterial spin labeling (CASL) was used to obtain an index of cerebral blood flow (ICBF) in the normal mouse brain and in an orthotopic mouse model of human U87 high-grade glioma at 8.5 T. Under the assumption of a constant tissue:blood partition coefficient for water in different tissues, the mean ICBF (n = 14) was found to be 50 +/- 9 mL/100g/min for tumor core and 209 +/- 11 mL/100g/min for normal tissue. The apparent T(1) (T(1app)) was 2.01 +/- 0.06 sec for tumor core and 1.66 +/- 0.03 sec for normal tissue. The ICBF and the T(1app) values were significantly different (P < 0.001) between these two regions. The detailed changes of ICBF and T(1app) in the transition from the tumor core through the tumor periphery to surrounding tissue were studied. Immunohistochemistry indicated that tumor vascularity was not uniform, with microvessel density highest in normal brain and the tissue surrounding the tumor and lowest in the tumor core. The large difference in ICBF between the tumor core and normal tissue suggests that this index might be useful for the assessment of the efficacy of antiangiogenic therapy.

Animals↗
PubMed2004

Fat fractions and spectral T2 values in vertebral bone marrow in HIV- and non-HIV-infected men: a 1H spectroscopic imaging study.

Fat fractions and spectral T2 values of fat and water within the vertebral marrow of non-HIV- and HIV-infected men were measured with the use of a Carr-Purcell-Meiboom-Gill (CPMG) line scan spectroscopic imaging sequence. The fat fraction for the HIV-infected men (0.29 +/- 0.08) was significantly lower (P < 0.05, Student's unpaired t-test) than the fat fraction found in non-HIV-infected men (0.40 +/- 0.12). The mean water and fat T2 values did not differ between the two groups, and did not show any systematic dependence on fat fraction over the wide range of fat fractions encountered in this study. The marrow water and fat T2 values measured with the CPMG approach were markedly longer than the spectral T2 values reported by other groups using the more common point-resolved spectroscopy (PRESS) and stimulated-echo acquisition mode (STEAM) acquisitions. Proton spectroscopic studies of vertebral marrow revealed differences between non-HIV- and HIV-infected men that may prove useful for studying the effects of this disease and/or antiretroviral agents on body composition.

Adult↗
PubMed2004

Quantification of water diffusion and relaxation times of human U87 tumors in a mouse model.

Assessing the potential of anti-cancer agents can be greatly facilitated by applying MRI methods to investigations with animal models. Quantitative diffusion imaging, T1, and T2 measurements may offer valuable information for understanding properties of the tumor and for evaluating new therapeutic approaches. The human U87 high-grade glial tumor is widely used for cancer investigations in orthotopic murine models. The physiological features of this model at the cellular and sub-cellular level have not, however, been well characterized by MRI. In this study, we measured the diffusion, T1 and T2 characteristics of water in the human U87 tumor at 8.5 T in an orthotopic murine model in vivo and analyzed their detailed changes in the transition from the tumor core through the tumor periphery, and out to surrounding tissue using custom developed radial profile analysis software. For the tumor bearing mice (n = 10), the mean average apparent diffusion coefficient (ADC) of the tumor core was 1.03 +/- 0.02 ( x 10(-3) mm2/s), while in the contralateral normal brain it was 0.73 +/- 0.03 ( x 10(-3) mm2/s). The mean T1 in tumor was 2.03 +/- 0.08 s and in normal brain tissue was 1.64 +/- 0.06 s. The mean T(2) in tumor was 0.062 +/- 0.002 s and in normal brain tissue was 0.048 +/- 0.001 s. The mean ADC, T1 and T2 of the tumor compared to normal tissue were significantly different (p < 0.005).

Animals↗
PubMed2004

Spatially selective T2 and T2 * measurement with line-scan echo-planar spectroscopic imaging.

Line-scan echo planar spectroscopic imaging (LSEPSI) is applied to quickly measure the T2 and T2* relaxation time constants in pre-selected 2D or 3D regions. Results from brain imaging studies at 3T suggest that the proposed method may prove valuable for both basic research (e.g., quantifying the changes of T2/T2* values in functional MRI with blood oxygenation level-dependent contrast) and clinical studies (e.g., measuring the T2' shortening due to iron deposition). The proposed spatially selective T2 and T2* mapping technique is especially well suited for studies, where T2/T2* quantification needs to be performed dynamically in a pre-selected 2D or 3D region.

Brain↗
PubMed2004

Fast spectroscopic imaging strategies for potential applications in fMRI.

Technical aspects of two general fast spectroscopic imaging (SI) strategies, one based on gradient echo trains and the other on spin echo trains, are reviewed within the context of potential applications in the field of functional magnetic resonance imaging (fMRI). Fast spectroscopic imaging of water may prove useful for identifying mechanisms underlying the blood oxygenation level dependence (BOLD) of the water signal during brain activation studies. Reasonably rapid mapping of changes in proton signals from brain metabolites, like lactate, creatine or even neurotransmitter associated metabolites like GABA, is substantially more challenging but technically feasible particularly as higher field strengths become available. Fast spectroscopic methods directed towards the 31P signals from phosphocreatine (PCr) and adenosine tri-phosphates (ATP) are also technically feasible and may prove useful for studying cerebral energetics within fMRI contexts.

Adult↗
PubMed2004

Detection of fetal lactate with two-dimensional-localized proton magnetic resonance spectroscopy.

BACKGROUND: Antenatal surveillance is inefficient for accurately detecting fetal compromise. A noninvasive technique for assessing fetal metabolic status would be useful for clinical management. CASE: Fetal magnetic resonance spectroscopy was performed at 20 weeks in a pregnancy complicated by severe intrauterine growth restriction to determine if lactate, a metabolite associated with fetal hypoxia, was present. Two-dimensional, single-slice proton magnetic resonance spectroscopy was carried out at 1.5 T using a volume-selective, double-spin echo technique. Lactate was detected in fetal back muscle. Fetal death occurred the next day. CONCLUSIONS: Although this initial report is purely experimental, further development of this technique may prove to be a valuable noninvasive tool in the management of suspected fetal hypoxia.

Adult↗
PubMed2004

Cognitive deficits and magnetic resonance spectroscopy in adult monozygotic twins with lead poisoning.

Seventy-one-year-old identical twin brothers with chronic lead poisoning were identified from an occupational medicine clinic roster. Both were retired painters, but one brother (J.G.) primarily removed paint and had a history of higher chronic lead exposure. Patella and tibia bone lead concentrations measured by K-X-ray fluorescence in each brother were 5-10 times those of the general population and about 2.5 times higher in J.G. than in his brother (E.G.). Magnetic resonance spectroscopy (MRS) studies examined N-acetylaspartate:creatine ratios, a marker of neuronal density. Ratios were lower in J.G. than in his brother. Scores on neurocognitive tests that assess working memory/executive function were below expectation in both twins. Short-term memory function was dramatically worse in J.G. than in his brother. These results demonstrate some of the more subtle long-term neurologic effects of chronic lead poisoning in adults. In particular, they suggest the presence of frontal lobe dysfunction in both twins, but more dramatic hippocampal dysfunction in the brother with higher lead exposure. The MRS findings are consistent with the hypothesis that chronic lead exposure caused neuronal loss, which may contribute to the impairment in cognitive function. Although a causal relation cannot be inferred, the brothers were genetically identical, with similar life experiences. Although these results are promising, further study is necessary to determine whether MRS findings correlate both with markers of lead exposure and tests of cognitive function. Nevertheless, the results point to the potential utility of MRS in determining mechanisms of neurotoxicity not only for lead but also for other neurotoxicants as well.

Aged↗
PubMed2004

Early experience alters brain function and structure.

OBJECTIVE: To investigate the effects of early experience on brain function and structure. METHODS: A randomized clinical trial tested the neurodevelopmental effectiveness of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP). Thirty preterm infants, 28 to 33 weeks' gestational age (GA) at birth and free of known developmental risk factors, participated in the trial. NIDCAP was initiated within 72 hours of intensive care unit admission and continued to the age of 2 weeks, corrected for prematurity. Control (14) and experimental (16) infants were assessed at 2 weeks' and 9 months' corrected age on health status, growth, and neurobehavior, and at 2 weeks' corrected age additionally on electroencephalogram spectral coherence, magnetic resonance diffusion tensor imaging, and measurements of transverse relaxation time. RESULTS: The groups were medically and demographically comparable before as well as after the treatment. However, the experimental group showed significantly better neurobehavioral functioning, increased coherence between frontal and a broad spectrum of mainly occipital brain regions, and higher relative anisotropy in left internal capsule, with a trend for right internal capsule and frontal white matter. Transverse relaxation time showed no difference. Behavioral function was improved also at 9 months' corrected age. The relationship among the 3 neurodevelopmental domains was significant. The results indicated consistently better function and more mature fiber structure for experimental infants compared with their controls. CONCLUSIONS: This is the first in vivo evidence of enhanced brain function and structure due to the NIDCAP. The study demonstrates that quality of experience before term may influence brain development significantly.

Brain↗
PubMed2004

Age-related vascular changes in the epiphysis, physis, and metaphysis: normal findings on gadolinium-enhanced MRI of piglets.

OBJECTIVE: We sought to study the normal enhancement patterns seen on MRIs of the epiphysis, physis, and metaphysis and age-related vascular changes in piglets using gadoteridol, a nonionic gadolinium chelate. MATERIALS AND METHODS: We quantitatively and qualitatively analyzed the normal changes on sequential T1-weighted images after the IV administration of gadoteridol. In an investigation approved by the research animal care committee at our hospital, we studied the proximal and distal femurs of 26 piglets 1-6 weeks old and correlated the enhanced images with findings on intermediate-weighted, T2-weighted, and gradient-recalled echo images and at histologic examination. RESULTS: We observed early enhancement of the epiphyseal vascular canals, the main physis, the physis of the secondary ossification center, and a metaphyseal band adjacent to the physis. Enhancement of the epiphyseal and metaphyseal marrow and of the epiphyseal cartilage was slower. In the epiphyseal cartilage, we saw three phases of enhancement: vascular, canalicular, and cartilaginous. As the piglets matured, enhancement of the epiphyseal cartilage decreased, and the epiphyseal vascular canals were less conspicuous. Physeal enhancement was greatest during the first week of life, declined at 3 weeks, and subsequently increased again as the physis came to lie adjacent to a larger segment of the epiphyseal ossification center. CONCLUSION: Gadoteridol-enhanced MRIs showed multiple cartilaginous and vascular structures of the growing skeleton. With maturity and progressive epiphyseal ossification, epiphyseal cartilage enhancement decreased, and physeal cartilage enhancement increased.

Aging↗
PubMed2003

CT versus MR in neonatal brain imaging at term.

BACKGROUND: Recent reports have highlighted the lifetime risk of malignancy from using ionizing radiation in pediatric imaging. Computed tomography (CT), which uses ionizing radiation, is employed extensively for neonatal brain imaging of term infants. Magnetic resonance (MR) provides an alternative that does not use ionizing radiation. OBJECTIVE: The purpose of this study was to assess the cross-modality agreement and interobserver agreement of CT and MR brain imaging of the term or near-term neonate. MATERIALS AND METHODS: Brain CT and MR images of 48 neonates were retrospectively reviewed by two pediatric neuroradiologists. CT and MR examinations had been obtained within 72 h of one another in all patients. CT was obtained with 5 mm collimation (KV=120, mAs=340). MR consisted of T1-weighted imaging (TR/TE=300/14; 4-mm slice thickness/1-mm gap), T2-weighted imaging (TR/TE/etl= 3000/126/16; 4-mm slice thickness/1-mm gap), and line scan diffusion imaging (LSDI) (TR/TE/b factor=1258/63/750; nominal 4-mm slice thickness/3-mm gap). The brain was categorized as normal or abnormal on both CT and MR. RESULTS: Ischemic injury was the most common brain abnormality demonstrated. McNemar's test indicated no significant difference between CT and MR test results for reader 1 (P=0.22) or reader 2 (P=0.45). The readers agreed on the presence or absence of abnormality on CT in 40 patients (83.3%) and on MR in 45 patients (93.8%). For CT, the kappa coefficient indicated excellent interobserver agreement (kappa=0.68), although the lower limit of the 95% confidence interval extends to kappa=0.55, which indicates only good-to-moderate agreement. For MR, the kappa coefficient indicated almost perfect interobserver agreement (kappa=0.88) with the 95% confidence interval extending to a lower limit of kappa=0.76, which represents excellent agreement. CONCLUSION. Because MR demonstrates findings similar to CT and has greater interobserver agreement, it appears that MR is a superior test to CT in determining brain abnormalities in the term neonate. Furthermore, since MR eliminates the use of ionizing radiation, a putative cause of malignancy, it should be the standard in neonatal brain imaging. Future efforts should be directed to improving neonatal access to MR to avoid the routine use of CT in infants.

Brain↗
PubMed2003

Feasibility of internally referenced brain temperature imaging with a metabolite signal.

The feasibility of using a metabolite signal as an internal reference for self-referenced temperature distribution measurement was examined. Line scan echo-planar spectroscopic imaging (LSEPSI) was applied to obtain quick multi-voxel spectroscopic measurements and to avoid possible spectral degradation from motion. Temperature distribution in a rabbit brain in vivo was successfully visualized by means of the chemical shift of water, which was measured by using naturally abundant (up to 10 mM) N-acetyl-aspartate (NAA) as the reference signal. Unlike the phase-mapping approach, this technique does not require a pixel-by-pixel subtraction. Therefore, in theory, it is more resistant to inter-scan motion or changes in susceptibility. The spatial and temporal resolutions of this technique are 1.5 cm3 and 4.5 min. A higher signal-to-noise ratio and optimization of the water and outer-volume suppression capabilities will be required to further enhance the temperature-mapping capabilities.

Animals↗