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Biomedical subjects

D G Norris

Publications and source records attributed to D G Norris.

At least 37 records · Page 2Linked to original sources

Velocity selective radiofrequency pulse trains.

The incorporation of velocity-encoding gradient pulses in RF-pulse trains is proposed and examined. Velocity selective perturbation is shown to be analogous in many respects to the well established use of trains of short RF-pulses for chemical shift selective perturbation. Velocity selective perturbation is viable in a biomedical setting only if additional RF refocusing pulses are inserted between the individual RF-pulse elements. Aspects of velocity selective excitation saturation and inversion are examined, and new inversion pulse trains proposed. The selective perturbation of both flowing and stationary spins is demonstrated in phantoms and possible biomedical applications of these pulse trains are discussed.

Magnetic Resonance Spectroscopy↗

Human rapid acquisition with relaxation enhancement imaging at 8 T without specific absorption rate violation.

A standard fast imaging sequence, rapid acquisition with relaxation enhancement (RARE), has been applied to human magnetic resonance at 8 T. RARE is known for its speed, good contrast and high RF power content. Highly T2 weighted images, the hallmark of RARE imaging, were acquired from the human brain. It is demonstrated that while T2 values may be reduced at 8 T, high quality RARE images could still be acquired at this field strength. Most importantly however, it is demonstrated that RARE images could be acquired without violating specific absorption rate (SAR) guidelines. Since it is well known that T2 weighted images are of significant value in clinical diagnosis, the implementation of RARE at this field strength will provide ultra high field MRI (UHFMRI) with a valuable imaging protocol at this field strength without exceeding SAR limitations.

Brain↗

MDEFT imaging of the human brain at 8 T.

T1-weighted images of the human brain obtained with the MDEFT sequence at 8 T are presented. These images are characterized by an excellent contrast and good signal to noise ratio. Importantly, results were obtained with adiabatic spin inversion and demonstrate that such pulses can be used even in the ultra high frequency (> 300 MHz) range. It is thus possible to obtain high quality results at this field strength without violating SAR guidelines.

Brain↗

GRASE imaging at 3 Tesla with template interactive phase-encoding.

A new method for ordering the phase-encoding gradient is proposed, and an application for short effective TE gradient- and spin-echo (GRASE) imaging is demonstrated. The proposed method calculates the phase-encoding order from the signal decay of a template scan (hence "template interactive phase-encoding" or TIPE). Computer simulations are used to compare the point spread functions of different phase-encoding orders giving short effective echo times (kb centric GRASE, centric GRASE, centric TIPE). The conventional centric phase-encoding order is also considered for GRASE. The conventional centric method is sensitive to both amplitude and phase modulation of the signal in k-space. The centric TIPE method gives the least amplitude modulation artifacts but is vulnerable to phase artifacts. The TIPE experiment was implemented on a 3 Tesla system. To the best of our knowledge, we present the first in vivo GRASE images at this field strength.

Artifacts↗

Use of short intertrial intervals in single-trial experiments: a 3T fMRI-study.

We investigated the detectability of task-related changes in the fMRI-signal in an averaged single trial design under systematic variation of intertrial intervals (ITI) in the range between 4 and 12 s. Investigation of the signal timecourses showed a shortening of the baseline period and subsequently a reduction in signal amplitude with decreasing ITI. The main finding is that effect size, i.e., the ratio of task-related signal changes and error variance remained approximately constant from ITI of 12 s down to 6 s. At ITI = 4 s, the effect size was reduced by about 50%. The effects of ITI reduction were comparable in all six cortical ROI which were analyzed. In two subcortical ROI, effect size was already reduced at longer ITI. At ITI = 4 s, the rising flank of the BOLD response was delayed compared to longer ITI. When the data were corrected for the temporal overlap of successive BOLD-responses, the signal amplitudes at ITI = 4 s were comparable to the amplitudes measured at an interval of 12 s. This indicated that the amplitude reduction was mainly due to a linear superposition of the contiguous BOLD-responses.

Adult↗

Characterization of middle cerebral artery occlusion infarct development in the rat using fast nuclear magnetic resonance proton spectroscopic imaging and diffusion-weighted imaging.

A nuclear magnetic resonance study of the middle cerebral artery occlusion in the rat is presented. Experiments were performed on seven animals before and after occlusion, which occurred in situ. The emphasis in this study was on evaluating rapid proton spectroscopic imaging. Data were acquired with experimental durations of between 4 and 15 minutes for a 32 by 32 spatial matrix, with 64 spectroscopic data points per spatial element. The spectroscopic data were interleaved with diffusion-weighted nuclear magnetic resonance water images of the same slice. The study was terminated at about 6 hours after occlusion. The brains were then frozen in liquid nitrogen for biochemical imaging. The results showed that the signal from N-acetyl aspartate decreased and that of lactate increased within the infarcted region. The temporal course of these intensity changes varied between animals. Nineteen cortical spreading depressions (CSD) were observed by electrophysiologic monitoring during the experiments. Of these, 11 could be unambiguously detected in the lactate images, and a further 3 were on the threshold of detectability. As only a single slice could be examined, it is possible that the centers of depression for the remaining 6 CSD were outside the slice. To the authors' knowledge, this is the first report of the measurement of CSD using proton spectroscopic imaging. Thus, it is shown that this method is valuable not only in following the continuous evolution of proton metabolites with a good spatial and temporal resolution, but also in observing transient phenomena which are believed to play an important role in the expansion of the infarcted territory.

Animals↗

Mechanism and echo time dependence of the fast response in fMR.

The fast response (FR) is an early reduction in the amplitude of the fMR signal occurring shortly after the onset of stimulation. Owing to its potential advantages in terms of temporal and spatial resolution, it may be of considerable significance in functional experiments. A model for the mechanism of the FR was developed which accounts for the fMRS finding that the amplitude of the dip decreases with increasing echo time. Two computer simulations that confirmed the predictions of the model and showed that it is possible to select optimal echo times for the detection of the FR were performed.

Computer Simulation↗

Fast proton spectroscopic imaging employing k-space weighting achieved by variable repetition times.

A k-space weighted spectroscopic imaging (SI) method is presented that allows a reduction in the total data acquisition time by up to 55% compared with standard SI. The k-space weighting is achieved by varying the repetition time, thus realizing an inherent apodization that corresponds to a circularly symmetric generalized Hamming filter. The flip angle is varied with the repetition time to enhance the signal-to-noise ratio. These techniques were employed using a short echo time of 10 ms. In vivo measurements on healthy rat brain at 4.7 T were conducted, obtaining two-dimensional spectroscopic imaging data from a 25 x 25 circularly reduced k-space area in as little as 5 min. The signal-to-noise ratio is sufficiently high to detect J-coupled resonances such as myo-inositol or glutamate/glutamine, demonstrating the ability to combine short acquisition times with comprehensive metabolic information. The T1 dependency of the apodization and the corresponding point spread function was evaluated by computer simulations. The achievable signal-to-noise ratio per unit time was compared with standard SI giving a parameter-dependent advantage of approximately 20% of the standard SI method.

Animals↗

Biexponential diffusion attenuation in various states of brain tissue: implications for diffusion-weighted imaging.

Diffusion-weighted single voxel experiments conducted at b-values up to 1 x 10(4) smm-2 yielded biexponential signal attenuation curves for both normal and ischemic brain. The relative fractions of the rapidly and slowly decaying components (f1, f2) are f1 = 0.80 +/- 0.02, f2 = 0.17 +/- 0.02 in healthy adult rat brain and f1 = 0.90 +/- 0.02, f2 = 0.11 +/- 0.01 in normal neonatal rat brain, whereas the corresponding values for the postmortem situation are f1 = 0.69 +/- 0.02, f2 = 0.33 +/- 0.02. It is demonstrated that the changes in f1 and f2 occur simultaneously to those in the extracellular and intracellular space fractions (fex, f(in)) during: (i) cell swelling after total circulatory arrest, and (ii) the recovery from N-methyl-D-aspartate induced excitotoxic brain edema evoked by MK-801, as measured by changes in the electrical impedance. Possible reasons for the discrepancy between the estimated magnitude components and the physiological values are presented and evaluated. Implications of the biexponential signal attenuation curves for diffusion-weighted imaging experiments are discussed.

Age Factors↗

Quantitative measurement of regional blood flow with gadolinium diethylenetriaminepentaacetate bolus track NMR imaging in cerebral infarcts in rats: validation with the iodo[14C]antipyrine technique.

NMR bolus track measurements were correlated with autoradiographically determined regional cerebral blood flow (rCBF). The NMR method is based on bolus infusion of the contrast agent gadolinium diethylenetriaminepentaacetate and high-speed T*2-sensitive NMR imaging. The first pass of the contrast agent through the image plane causes a transient decrease of the signal intensity. This time course of the signal intensity is transformed into relative concentrations of the contrast agent in each pixel. The mean transit time and relative blood flow and volume are calculated from such indicator dilution curves. We investigated whether this NMR technique correctly expresses the relative rCBF. The relative blood flow data, calculated from NMR bolus track experiments, and the absolute values of iodo[14C]antipyrine autoradiography were compared. A linear relationship was observed, indicating the proportionality of the transient NMR signal change with CBF. Excellent interindividual reproducibility of calibration constants is observed (r = 0.963). For a given NMR protocol, bolus track measurements calibrated with autoradiography after the experiment allow determination of absolute values for rCBF and regional blood volume.

Animals↗

A fast method for in vivo lactate imaging.

A robust method for fast lactate imaging is presented using a combination of a lactate editing sequence and a one-shot imaging experiment. The lactate editing method is based on manipulation of the phase of the lactate CH3 signal via J-modulation. This is applied as a preparation experiment to the U-FLARE imaging sequence. Phantom experiments are presented in which the quality of water and lipid suppression is established. Edited lactate images with a spatial resolution of 3 microL and total measuring time of 15.8 min are shown. These were obtained from a hemispherical ischemia in the gerbil brain. The images are compared with diffusion-weighted water images.

Animals↗

Evolution of regional changes in apparent diffusion coefficient during focal ischemia of rat brain: the relationship of quantitative diffusion NMR imaging to reduction in cerebral blood flow and metabolic disturbances.

Middle cerebral artery occlusion was performed in rats while the animals were inside the nuclear magnetic resonance (NMR) tomograph. Successful occlusion was confirmed by the collapse of amplitude on an electrocorticogram. The ultrafast NMR imaging technique UFLARE was used to measure the apparent diffusion coefficient (ADC) immediately after the induction of cerebral ischemia. ADC values of normal cortex and caudate-putamen were 726 +/- 22 x 10(-6) mm2/s and 659 +/- 17 x 10(-6) mm2/s, respectively. Within minutes of occlusion, a large territory with reduced ADC became visible in the ipsilateral hemisphere. Over the 2 h observation period, this area grew continuously. Quantitative analysis of the ADC reduction in this region showed a gradual ADC decrease from the periphery to the core, the lowest ADC value amounting to about 60% of control. Two hours after the onset of occlusion, the regional distribution of ATP and tissue pH were determined with bioluminescence and fluorescence techniques, respectively. There was a depletion of ATP in the core of the ischemic territory (32 +/- 20% of the hemisphere) and an area of tissue acidosis (57 +/- 19% of the hemisphere) spreading beyond that of ATP depletion. Regional CBF (rCBF) was measured autoradiographically with the iodo[14C]antipyrine method. CBF gradually decreased from the periphery to the ischemic core, where it declined to values as low as 5 ml 100 g-1. When reductions in CBF and in ADC were matched to the corresponding areas of energy breakdown and of tissue acidosis, the region of energy depletion corresponded to a threshold in rCBF of 18 +/- 14 ml 100 g-1 min-1 and to an ADC reduction to 77 +/- 3% of control. Tissue acidosis corresponded to a flow value below 31 +/- 11 ml 100 g-1 min-1 and to an ADC value below 90 +/- 4% of control. Thus, the quantification of ADC in the ischemic territory allows the distinction between a core region with total breakdown of energy metabolism and a corona with normal energy balance but severe tissue acidosis.

Adenosine Triphosphate↗

Magnetization transfer affects the proton creatine/phosphocreatine signal intensity: in vivo demonstration in the rat brain.

The effect of off-resonance preirradiation on proton spectra acquired from the healthy rat brain at 4.7 T is examined using a PRESS sequence. The creatine/phosphocreatine (Cr/PCr) signal at 3.0 ppm decreases in signal intensity for offset frequencies between +/- 10 kHz. This cannot be explained by RF bleedover, but is attributed to magnetization transfer between two pools of Cr/PCr, one with a long T2 relaxation time giving the observed NMR signal, the other corresponding to a broad resonance line being completely or partially saturated by off-resonance preirradiation. Possible interpretations of these results are discussed.

Animals↗

Detection of apparent restricted diffusion in healthy rat brain at short diffusion times.

The application of bipolar diffusion sensitizing gradient pulses to significantly reduce the diffusion time is described. This approach is combined with the rapid U-FLARE imaging sequence. Three diffusion-sensitized types of experiments are compared and their suitability for detecting restricted diffusion is discussed. Experiments using a modification of the diffusion weighting by varying the diffusion time between 1.6 and 6.0 ms obtained nonmonoexponential signal attenuation curves from both healthy brains and postmortem. This behavior is indicative of restricted diffusion, but as it is detectable only at short diffusion times, in contrast to a restriction due to impermeable barriers, we have termed this "apparent restriction."

Animals↗

Health and infarcted brain tissues studied at short diffusion times: the origins of apparent restriction and the reduction in apparent diffusion coefficient.

The significance of NMR water diffusion measurements performed at short diffusion times (< 10 ms) for brain tissue is examined. An apparent restriction to diffusion for both healthy and cytotoxically edematous tissue is shown: cytotoxic edema lengthens the diffusion time at which this phenomenon is visible. The dramatic reduction in apparent diffusion coefficient (ADC) observed in the core of cytotoxic edema is explained in terms of the enclosure of extracellular water in non-contiguous pockets in conjunction with the shift of water from the extra-to the intracellular space. The model presented provides an explanation for the ADC reduction without recourse to changes in the cell membrane permeability to water, or unrealistic values for the extra- and intracellular diffusion coefficients.

Animals↗

Pretransplant chemotherapy in pediatric hepatocellular carcinoma.

The prognosis for pediatric patients with hepatocellular carcinoma is poor, except for fewer than half the patients, who can be rendered disease-free with conventional liver resection. Multicentric, bilobar liver cancer remains unresectable, even after radiation and chemotherapy. Liver transplantation alone for primary hepatic cancer has had limited success. Chemotherapy has been reserved for use after transplantation, with little demonstrable benefit. A pilot program of pretransplant chemotherapy was undertaken. Four adolescent patients with unresectable, multicentric, bilobar hepatocellular carcinoma were staged noninvasively, underwent chemotherapy followed by a final staging laparotomy, and then had liver transplantation. Three of the four patients survived and have no evidence of recurrence 84, 67, and 47 months after diagnosis and 76, 65, and 44 months after transplantation. Pretransplant chemotherapy has four potential advantages: (1) minimized risk of posttransplant opportunistic infections, (2) less tumor bulk at the time of transplantation, (3) fewer local recurrences, and (4) a lower rate of metastasis.

Adolescent↗

Incidence of apparent restricted diffusion in three different models of cerebral infarction.

High speed magnetic resonance imaging (MRI) and short diffusion times are used to investigate the appearance of restricted diffusion in three different models of cerebral infarction. The models are: the middle cerebral artery occlusion (MCAO) model in the rat, the carotid occlusion model in the gerbil, and the Rose Bengal microvascular occlusion model in the rat. All three were investigated for 16 b-values equally spaced between 10 and 1510 s/mm2 using two distinct experiments. In the ct (constant time) experiment, the diffusion time was held constant at 11.7 ms while the b-value was varied with the gradient strength. In the cg (constant gradient) experiment, the gradient strength was held constant and the b-value increased by varying the diffusion time from 4.4 to 11.7 ms. A monoexponential decay of the signal intensity with b-value in the ct experiment accompanied by nonmonoexponential (NME) decay in the cg experiment is indicative of restricted diffusion. As this phenomenon is detectable only at short diffusion times, it cannot be due to restriction by impermeable membranes, and we have thus termed this apparent restriction. For the MCAO model and the carotid occlusion model, apparent restriction was found both inside the infarct territory and in some regions outside it. No definite evidence for restriction was found for the Rose Bengal model, which was, however, only studied from 24 h post-insult.

Animals↗

Fast perfluorocarbon imaging using 19F U-FLARE.

The application of an ultra-fast low angle RARE technique for the 19F imaging of perfluorocarbons (PFCs) used as temporary blood substitutes is described. This sequence is attractive for fast 19F imaging studies that measure the biodistribution of PFCs in vivo, due to its high signal-to-noise ratio. Extensions of this technique for the chemical shift selective measurement of fluorine T1 values are presented. Using the linear dependence between the oxygen partial pressure (pO2) and the T1 relaxation rate of PFC resonances this technique makes possible the fast in vivo measurement of oxygen tension. Using the sequence in a diffusion sensitized form 19F measurements of the diffusion constants of PFCs are also presented. Phantom experiments to test the methods, and in vivo images obtained in rat studies are given and discussed.

Animals↗