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Robert V Mulkern

Publications and source records attributed to Robert V Mulkern.

36 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Double inversion black-blood fast spin-echo imaging of the human heart: a comparison between 1.5T and 3.0T.

PURPOSE: To evaluate the effectiveness of blood suppression and the quality of black-blood cardiac images acquired at 3.0 Tesla using a double-inversion recovery fast spin-echo sequence by comparing data acquired at 3.0T to data acquired at 1.5T. MATERIALS AND METHODS: Black-blood T2-weighted fast spin-echo images of the heart were acquired from five normal volunteers at 1.5T and five normal volunteers at 3.0T. Region-of-interest signal intensity measurements were performed at several locations in the suppressed blood regions of the left and right ventricles and around the left ventricle walls to assess the effectiveness and uniformity of the blood suppression, the myocardial signal-to-noise ratio (SNR), and the signal uniformity at both field strengths. B1 field maps were produced in phantoms and in subjects at both field strengths. RESULTS: Blood suppression performance is equivalent at 1.5T and 3.0T. The improvement in SNR at 3.0T compared with 1.5T is less than has been predicted in previous studies. The signal uniformity is significantly poorer at 3.0T than at 1.5T due to dielectric effects and shorter radio frequency wavelengths (P < 0.005). CONCLUSION: Spin-echo and spin-echo echo-train sequences that perform well at 1.5T will produce large signal variations in the chest cavity at 3.0T without modifications. B1 insensitive methods must be explored and implemented for spin-echo sequences to fully realize the advantages of using these sequences for high-field MRI.

Blood↗

Characterization of normal brain and brain tumor pathology by chisquares parameter maps of diffusion-weighted image data.

OBJECTIVE: To characterize normal and pathologic brain tissue by quantifying the deviation of diffusion-related signal from a simple monoexponential decay, when measured over a wider than usual range of b-factors. METHODS AND MATERIALS: Line scan diffusion imaging (LSDI), with diffusion weighting at multiple b-factors between 100 and 5000 s/mm(2), was performed on 1.5 T clinical scanners. Diffusion data of single slice sections were acquired in five healthy subjects and 19 brain tumor patients. In-patients, conventional T2-weighted and contrast-enhanced T1-weighted images were obtained for reference purposes. The chisquare (chi(2)) error parameter associated with the monoexponential fits of the measured tissue water signals was then used to quantify the departure from a simple monoexponential signal decay on a pixel-by-pixel basis. RESULTS: Diffusion-weighted images over a wider b-factor range than typically used were successfully obtained in all healthy subjects and patients. Normal and pathologic tissues demonstrated signal decays, which clearly deviate from a simple monoexponential behavior. The chi(2) of cortical and deep grey matter was considerably lower than in white matter. In peritumoral edema, however, chi(2) was 68% higher than in normal white matter. In highly malignant brain tumors, such as glioblastoma multiforme (GBM) or anaplastic astrocytoma, chi(2) values were on average almost 400% higher than in normal white matter, while for one low grade astrocytoma and two cases of metastasis, chi(2) was not profoundly different from the chi(2) value of white matter. Maps of the chi(2) values provide good visualization of spatial details. However, the tumor tissue contrast generated appeared in many cases to be different from the enhancement produced by paramagnetic contrast agents. For example, in cases where the contrast agent only highlighted the rim of the tumor, chi(2) enhancement was present within the solid part of the tumor. CONCLUSION: The deviation from a purely monoexponential diffusion signal decay becomes evident as diffusion encoding is extended well beyond the normal range. The chi(2) error parameter as a measure of this deviation seems to provide sufficient lesion contrast to permit differentiation of malignant brain tumors from normal brain tissue.

Adult↗

A functional magnetic resonance imaging study of paced finger tapping in children.

Fourteen typically developing children from 7.9-11.3 years in age were studied with functional magnetic resonance imaging to identify the cerebral loci involved in performance of paced finger tapping by children. Each child performed two bimanual alternating paced finger-tapping tasks. In the first, paced finger tapping was conducted to external 3-Hz pacing provided by a metronome. In the second, the metronome was turned off and finger tapping continued while each child tried to maintain the 3-Hz rhythm by self pacing. Individual and group data were analyzed with statistical parametric mapping techniques that resulted in activation maps for the two tasks. Metronome tapping produced activation of the posterior regions of both superior temporal gyri, both primary sensorimotor cortices, anterodorsomedial cerebellum and supplementary motor area. Self-tapping resulted in recruitment of pre-supplementary motor area and cerebellum in addition to bilateral supplementary motor area and primary sensorimotor cortical activation. Bimanual alternating paced finger tapping performed by children activates a neural network involving primary motor cortex, supplementary motor area, and cerebellum. Posterior superior temporal gyrus may be important for encoding auditory information, and presupplementary motor area and midline cerebellum play an important role in self-paced finger tapping.

Age Factors↗

Activation of peripheral excitatory amino acid receptors decreases the duration of local anesthesia.

BACKGROUND: Postsurgical wound infiltration with the -methyl-d-aspartate receptor antagonist ketamine and bupivacaine can significantly prolong the duration of local anesthesia. One possible mechanism for this effect is that increased glutamate concentrations, caused by tissue damage, sensitize nociceptive primary afferent fibers through activation of peripheral excitatory amino acid receptors. METHODS: The effect of intramuscular injection of hyper-tonic glutamate (1,000 mm), dextrose (1,400 mm), glutamate (1,000 mm) with the broad spectrum excitatory amino acid receptor antagonist kynurenate (100 mm), or isotonic saline (155 mm) on the duration of masseter muscle afferent fiber blockade after lidocaine (37 mm [1%], 10 microl) infiltration, on muscle edema formation and on muscle blood flow was examined. RESULTS: Injection of either glutamate or dextrose significantly shortened the duration of lidocaine blocks compared with isotonic saline; however, block duration was significantly shorter after glutamate than after dextrose. Injection of glutamate, but not isotonic saline, dextrose, or glutamate with kynurenate, significantly decreased the mechanical threshold of muscle afferent fibers. Injection of glutamate, dextrose, or glutamate with kynurenate produced equivalent large, long-lasting (> 60 min) edemas with high initial peak extracellular water content. Peak extracellular water decreased more rapidly when kynurenate was coinjected with glutamate. Both glutamate and dextrose significantly increased muscle blood flow for 30 min after injection. Glutamate-induced increases in blood flow were attenuated by kynurenate. CONCLUSIONS: These results suggest that shortened lidocaine block durations observed after glutamate injection into the masseter muscle result from sensitization of afferent fibers as well as increases of peak extracellular water content and blood flow in masseter muscle. These effects of glutamate are mediated in part through activation of peripheral excitatory amino acid receptors.

Anesthetics, Local↗

Detection of prostate cancer by integration of line-scan diffusion, T2-mapping and T2-weighted magnetic resonance imaging; a multichannel statistical classifier.

A multichannel statistical classifier for detecting prostate cancer was developed and validated by combining information from three different magnetic resonance (MR) methodologies: T2-weighted, T2-mapping, and line scan diffusion imaging (LSDI). From these MR sequences, four different sets of image intensities were obtained: T2-weighted (T2W) from T2-weighted imaging, Apparent Diffusion Coefficient (ADC) from LSDI, and proton density (PD) and T2 (T2 Map) from T2-mapping imaging. Manually segmented tumor labels from a radiologist, which were validated by biopsy results, served as tumor "ground truth." Textural features were extracted from the images using co-occurrence matrix (CM) and discrete cosine transform (DCT). Anatomical location of voxels was described by a cylindrical coordinate system. A statistical jack-knife approach was used to evaluate our classifiers. Single-channel maximum likelihood (ML) classifiers were based on 1 of the 4 basic image intensities. Our multichannel classifiers: support vector machine (SVM) and Fisher linear discriminant (FLD), utilized five different sets of derived features. Each classifier generated a summary statistical map that indicated tumor likelihood in the peripheral zone (PZ) of the prostate gland. To assess classifier accuracy, the average areas under the receiver operator characteristic (ROC) curves over all subjects were compared. Our best FLD classifier achieved an average ROC area of 0.839(+/-0.064), and our best SVM classifier achieved an average ROC area of 0.761(+/-0.043). The T2W ML classifier, our best single-channel classifier, only achieved an average ROC area of 0.599(+/-0.146). Compared to the best single-channel ML classifier, our best multichannel FLD and SVM classifiers have statistically superior ROC performance (P=0.0003 and 0.0017, respectively) from pairwise two-sided t-test. By integrating the information from multiple images and capturing the textural and anatomical features in tumor areas, summary statistical maps can potentially aid in image-guided prostate biopsy and assist in guiding and controlling delivery of localized therapy under image guidance.

Algorithms↗

Normal and ischemic epiphysis of the femur: diffusion MR imaging study in piglets.

PURPOSE: To evaluate normal diffusion characteristics in the femur in piglets and changes in diffusion with increasing duration of femoral head ischemia. MATERIALS AND METHODS: Normal epiphyses, physes, and metaphyses of piglets were evaluated with line-scan diffusion imaging (n = 12) and diffusion-tensor imaging (n = 4). Apparent diffusion coefficient (ADC) differences between normal proximal and distal femoral structures, epiphyseal and physeal cartilage, and epiphyseal and metaphyseal marrow were compared (Mann-Whitney test). Short-term femoral ischemia was investigated after maximal abduction of the hips for 3 hours (n = 6); ADCs before and after abduction were compared (Wilcoxon signed rank test). Prolonged ischemia was investigated with placement of a ligature around the neck of a femur (n = 7); the ADC of the femur in this condition was compared (Wilcoxon signed rank test) with that of the normal contralateral femur. Changes in ADC ratios at three durations of ischemia (Kruskal-Wallis test) were compared. RESULTS: ADC was greater in epiphyseal cartilage (mean +/- 1 SD, 1.62 x 10(-3) mm2/sec +/- 0.38) than it was in physeal cartilage (1.28 x 10(-3) mm2/sec +/- 0.31) (P <.007) and greater in epiphyseal marrow (1.26 x 10(-3) mm2/sec +/- 0.38) than it was in metaphyseal marrow (0.91 x 10(-3) mm2/sec +/- 0.35) (P <.001). There was columnar arrangement of tensors in the physis. ADC decreased 26% after 3 hours of maximal abduction. After femoral neck ligature, ADC increased a mean of 27% after 6 hours and a mean of 75% after 96 hours. CONCLUSION: Normal line-scan diffusion imaging findings indicate relative restriction of diffusion in the metaphysis and parallel orientation of tensors in the physis. Diffusion is initially restricted with decreased blood flow but increases if ischemia lasts longer.

Animals↗

Reduced intravertebral bone marrow fat in HIV-infected men.

OBJECTIVE: To measure intravertebral bone marrow fat in HIV-infected men. DESIGN: A cross-sectional study of HIV-positive men, subcategorized by lipodystrophy and antiretroviral status, and healthy age- and body mass index (BMI)-matched HIV-negative controls. SETTING: A tertiary care academic medical institution. PATIENTS: Fifteen HIV-infected men and nine age- and BMI-matched healthy control subjects were recruited for bone density, intravertebral bone marrow fat, and body composition measurements. METHODS: Magnetic resonance spectroscopy was used to measure intravertebral marrow fat. Quantitative computed tomography was used to quantify visceral and subcutaneous fat. Dual energy X-ray absorptiometry was used to determine lumbar spine bone density. Statistical comparisons were performed according to HIV, lipodystrophy, and protease inhibitor (PI) exposure status. RESULTS: Intravertebral marrow fat was reduced in HIV-infected men (N = 15) compared with healthy HIV-negative controls (N = 9) (28.5 +/- 8.0 versus 37.3 +/- 12.5%, P = 0.04). Intravertebral bone marrow fat was most severely reduced in HIV-infected men with lipodystrophy compared with healthy HIV-negative controls (25.6 +/- 8.8% versus 37.3 +/- 12.5%, P = 0.04). Furthermore, nelfinavir (P = 0.02) was associated with decreased intravertebral marrow fat and indinavir (P < 0.05) was associated with increased intravertebral marrow fat in HIV-infected subjects. CONCLUSION: We demonstrated reduced intravertebral marrow fat in HIV-infected men using magnetic resonance spectroscopy. Notably, reduced marrow fat occurred in the setting of reduced bone density and may be affected by specific PI and lipodystrophy status. Further studies are necessary to determine the relationship between marrow fat and osteopenia and the effect of antiretroviral therapy on marrow fat in this population.

Absorptiometry, Photon↗

Magnetic resonance relaxivity of dendrimer-linked nitroxides.

The relaxivity and bioreduction rates of eight dendrimer-linked nitroxides varying in the number of nitroxides per molecule were measured and the potential use of these compounds as MR contrast agents was demonstrated. The T(1) and T(2) relaxivities, measured at room temperature and 1.5 T, varied linearly with the number of nitroxides per molecule for compounds with up to 16 nitroxides per molecule. Fourth-generation polypropylenimide- (DAB) and third-generation polyamidoamine- (PAMAM) dendrimer-linked nitroxides were found to have greater relaxivity than gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). The greater number of nitroxides per dendrimer increased relaxivity over that of a single nitroxide, allowing a decreased dose to achieve differential contrast with MR evaluations. Rates of nitroxide bioreduction were below detection threshold using EPR spectroscopy for generation 2 dendrimers and higher. A pilot assessment of in vivo cartilage uptake that compared intraarticular injection of three structurally different dendrimer-linked nitroxides with Gd-DTPA and with saline demonstrated high affinity of the DAB-dendrimer-linked nitroxides for normal rabbit articular cartilage. From these results, it is evident that target-specific dendrimer-linked nitroxides can be designed.

Animals↗