Biomedical subjects

Robert V Mulkern

Publications and source records attributed to Robert V Mulkern.

At least 19 recordsLinked to original sources

PubMed2006

Complementary aspects of diffusion imaging and fMRI; I: structure and function.

Studying the intersection of brain structure and function is an important aspect of modern neuroscience. The development of magnetic resonance imaging (MRI) over the last 25 years has provided new and powerful tools for the study of brain structure and function. Two tools in particular, diffusion imaging and functional MRI (fMRI), are playing increasingly important roles in elucidating the complementary aspects of brain structure and function. In this work, we review basic technical features of diffusion imaging and fMRI for studying the integrity of white matter structural components and for determining the location and extent of cortical activation in gray matter, respectively. We then review a growing body of literature in which the complementary aspects of diffusion imaging and fMRI, applied as separate examinations but analyzed in tandem, have been exploited to enhance our knowledge of brain structure and function.

Brain Diseases↗

PubMed2006

Biexponential characterization of prostate tissue water diffusion decay curves over an extended b-factor range.

Detailed measurements of water diffusion within the prostate over an extended b-factor range were performed to assess whether the standard assumption of monoexponential signal decay is appropriate in this organ. From nine men undergoing prostate MR staging examinations at 1.5 T, a single 10-mm-thick axial slice was scanned with a line scan diffusion imaging sequence in which 14 equally spaced b factors from 5 to 3,500 s/mm(2) were sampled along three orthogonal diffusion sensitization directions in 6 min. Due to the combination of long scan time and limited volume coverage associated with the multi-b-factor, multidirectional sampling, the slice was chosen online from the available T2-weighted axial images with the specific goal of enabling the sampling of presumed noncancerous regions of interest (ROIs) within the central gland (CG) and peripheral zone (PZ). Histology from prescan biopsy (n=9) and postsurgical resection (n=4) was subsequently employed to help confirm that the ROIs sampled were noncancerous. The CG ROIs were characterized from the T2-weighted images as primarily mixtures of glandular and stromal benign prostatic hyperplasia, which is prevalent in this population. The water signal decays with b factor from all ROIs were clearly non-monoexponential and better served with bi- vs. monoexponential fits, as tested using chi(2)-based F test analyses. Fits to biexponential decay functions yielded intersubject fast diffusion component fractions in the order of 0.73+/-0.08 for both CG and PZ ROIs, fast diffusion coefficients of 2.68+/-0.39 and 2.52+/-0.38 microm(2)/ms and slow diffusion coefficients of 0.44+/-0.16 and 0.23+/-0.16 um(2)/ms for CG and PZ ROIs, respectively. The difference between the slow diffusion coefficients within CG and PZ was statistically significant as assessed with a Mann-Whitney nonparametric test (P<.05). We conclude that a monoexponential model for water diffusion decay in prostate tissue is inadequate when a large range of b factors is sampled and that biexponential analyses are better suited for characterizing prostate diffusion decay curves.

Aged↗

PubMed2006

Effects of bupivacaine and tetrodotoxin on carrageenan-induced hind paw inflammation in rats (Part 1): hyperalgesia, edema, and systemic cytokines.

BACKGROUND: Local anesthetics exert antiinflammatory actions. To elucidate potential mechanisms, the authors examined effects of bupivacaine or tetrodotoxin, administered to rats by ipsilateral or contralateral sciatic blockade or systemically, on carrageenan-induced hind paw hyperalgesia, edema, and stimulated cytokine production in circulating blood cells. METHODS: Twelve groups of rats (n = 9-12) received injections in three sites: (1) right or left hind paw (carrageenan or saline), (2) left sciatic block, and (3) systemically (subcutaneously in the upper back). Sciatic and systemic injections were performed with epinephrine plus bupivacaine, tetrodotoxin, or saline; injections were repeated 6 h later. Fifteen hours later, hyperalgesia and/or sensory and motor block were assessed behaviorally, and paw edema was quantified by magnetic resonance imaging. Stimulated production of tumor necrosis factor alpha, interleukin 10, and interleukin 1beta in whole blood cultures was measured by enzyme-linked immunosorbent assay. RESULTS: Either ipsilateral or contralateral sciatic blocks using either bupivacaine or tetrodotoxin reduced carrageenan-induced edema and hyperalgesia. Systemic bupivacaine and tetrodotoxin were ineffective in preventing edema and hyperalgesia. Bupivacaine was effective in suppressing systemic tumor necrosis factor alpha and interleukin 1beta by all three routes, whereas tetrodotoxin was ineffective by all three routes. CONCLUSION: Bupivacaine and tetrodotoxin, via a contralateral or ipsilateral sciatic block, attenuate local inflammatory edema and hyperalgesia induced by hind paw injection of carrageenan in rats. Mechanisms underlying contralateral effects of sciatic blockade remain unexplained. Bupivacaine inhibits carrageenan-evoked systemic cytokine production by a mechanism not shared by tetrodotoxin; this action may involve tetrodotoxin-resistant sodium channels or a variety of non-sodium-channel targets.

Animals↗

PubMed2006

Strategies for inner volume 3D fast spin echo magnetic resonance imaging using nonselective refocusing radio frequency pulses.

Fast spin echo (FSE) trains elicited by nonselective "hard" refocusing radio frequency (RF) pulses have been proposed as a means to enable application of FSE methods for high-resolution 3D magnetic resonance imaging (MRI). Hard-pulse FSE (HPFSE) trains offer short (3-4 ms) echo spacings, but are unfortunately limited to imaging the entire sample within the coil sensitivity thus requiring lengthy imaging times, consequently limiting clinical application. In this work we formulate and analyze two general-purpose combinations of 3D HPFSE with inner volume (IV) MR imaging to circumvent this limitation. The first method employs a 2D selective RF excitation followed by the HPFSE train and focuses on required properties of the spatial excitation profile with respect to limiting RF pulse duration in the 5-6 ms range. The second method employs two orthogonally selective 1D RF excitations (a 90x degrees - 180y degrees pair) to generate an echo from magnetization within the volume defined by their intersection. Subsequent echoes are formed via the HPFSE train, placing the focus of the method on (a) avoiding spurious echoes that may arise from transverse magnetization located outside the slab intersection when it is unavoidably affected by the nonselective refocusing pulses and (b) avoiding signal losses due to the necessarily different spacing (in time) of the RF pulse applications. The performance of each method is experimentally measured using Carr-Purcell-Meiboom-Gill (CPMG) multi-echo imaging, enabling examination of the magnetization evolution throughout the echo train. The methods as implemented achieve 95% to 97% outer volume signal suppression, and higher suppression appears to be well within reach, by further refinement of the selective RF excitations. Example images of the human brain and spine are presented with each technique. We conclude that the SNR efficiency of volume imaging in conjunction with the short echo spacing afforded by hard pulse trains enables high-resolution 3D HPFSE MRI of a small field-of-view (FOV) with minimal aliasing artifact.

Algorithms↗

PubMed2006

Regional brain development in serial magnetic resonance imaging of low-risk preterm infants.

OBJECTIVE: MRI studies have shown that preterm infants with brain injury have altered brain tissue volumes. Investigation of preterm infants without brain injury offers the opportunity to define the influence of early birth on brain development and provide normative data to assess effects of adverse conditions on the preterm brain. In this study, we investigated serial MRI of low-risk preterm infants with the aim to identify regions of altered brain development. METHODS: Twenty-three preterm infants appropriate for gestational age without magnetic resonance-visible brain injury underwent MRI twice at 32 and at 42 weeks' postmenstrual age. Fifteen term infants were scanned 2 weeks after birth. Brain tissue classification and parcellation were conducted to allow comparison of regional brain tissue volumes. Longitudinal brain growth was assessed from preterm infants' serial scans. RESULTS: At 42 weeks' postmenstrual age, gray matter volumes were not different between preterm and term infants. Myelinated white matter was decreased, as were unmyelinated white matter volumes in the region including the central gyri. The gray matter proportion of the brain parenchyma constituted 30% and 37% at 32 and 42 weeks' postmenstrual age, respectively. CONCLUSIONS: This MRI study of preterm infants appropriate for gestational age and without brain injury establishes the influence of early birth on brain development. No decreased cortical gray matter volumes were found, which is in contrast to findings in preterm infants with brain injury. Moderately decreased white matter volumes suggest an adverse influence of early birth on white matter development. We identified a sharp increase in cortical gray matter volume in preterm infants' serial data, which may correspond to a critical period for cortical development.

Brain↗

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↗

PubMed2005

Magnetic resonance spectroscopy-guided transperineal prostate biopsy and brachytherapy for recurrent prostate cancer.

Brachytherapy targeted to the peripheral zone with magnetic resonance imaging (MRI) guidance is a prostate cancer treatment option with potentially fewer complications than other treatments. Follow-up MRI when failure is suspected is, however, difficult because of radiation-induced changes. Furthermore, MR spectroscopy (MRS) is compromised by susceptibility artifacts from radioactive seeds in the peripheral zone. We report a case in which combined MRI/MRS was useful for the detection of prostate cancer in the transitional zone in patients previously treated with MR-guided brachytherapy. We propose that MRI/MRS can help detect recurrent prostate cancer, guide prostate biopsy, and help manage salvage treatment decisions.

Biopsy↗

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↗