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Biomedical subjects

D G Norris

Publications and source records attributed to D G Norris.

At least 19 recordsLinked to original sources

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

Fast proton spectroscopic imaging using the sliced k-space method.

The use of one-shot imaging methods for proton spectroscopic imaging (1H-SI) is examined. In particular the acquisition of Kx x Ky x Nt data points by means of Nt excitations, each acquiring a Kx x Ky k-space slice, is advocated. A number of strategies for realising this experiment, and combining it with water suppression and volume-selection are proposed. The practical implementation at 4.7 T for 1H-SI of the rat brain is described. Experimental results from a 32 x 32 spatial matrix with Nt = 64 are presented. Spectra obtained from volumes as low as 3.5 microliters and within measuring times of as little as 3.8 min are shown. In these choline, creatine/phosphocreatine and N-acetylaspartate are all clearly visible.

Animals

Dynamic imaging with T2* contrast using U-FLARE.

Dynamic changes in T2* in the rat brain induced by the injection of Gd-DTPA are monitored using the U-FLARE sequence. Sensitivity to T2* is easily introduced into this sequence and may be freely varied. The images obtained display an adequate spatial resolution and contrast, for a temporal resolution of 1 s. Intensity-time curves and parametric images of regional cerebral blood flow (rCBV) are presented for three different blood pCO2 values. The results presented clearly demonstrate that U-FLARE is a viable method for dynamically measuring changes in T2*, and thus has application in imaging of both perfusion and functional activation.

Animals

On the application of ultra-fast RARE experiments.

The ultra-fast application of the RARE experiment is described in detail, with special emphasis on its multifarious applications with preparation experiments that produce transverse magnetization. The factors affecting the temporal evolution of the magnetization during the experiment are described, and the implications for the slice profile when using a Gaussian refocusing pulse are experimentally examined. The choice of phase-encoding scheme for use with preparation experiments is discussed, as is the use of various phase-encoding schemes to reduce line broadening in the phase-encoding direction if a number of averages are acquired. An explanation for the decomposition of the echo are into two components if the read gradient is imbalanced is given, and the experimental conditions necessary for the coherent addition of these two echo groups are described. An alternative sequence that removes one of these groups from the acquisition window is proposed. The sensitivity of the sequence to flow and motion is investigated, and the drastic loss of signal in this situation explained. The in vivo and in vitro application of preparation experiments leading to the accurate measurement of T1, T2, diffusion constant, and magnetization transfer characteristics is presented. The implementation of zoom-imaging using spin- and stimulated-echo preparation is described, and 3D in vivo spin-echo zoom images are presented. Simple phantom experiments demonstrating the feasibility of chemical-shift selective and spectroscopic imaging are also given.

Animals

Ultrafast low-angle RARE: U-FLARE.

The subsecond application of the RARE technique is described. Two possible methods of implementation are discussed, one in which T2 contrast is manipulated by temporal reordering of the phase-encoding gradient, and the other in which the phase-encoding order is held constant and the contrast is manipulated by means of a spin-echo preparation experiment. In vivo images obtained with the latter method are presented and applications of the sequence discussed.

Animals

The spectrum of eosinophilic gastroenteritis. Report of six pediatric cases and review of the literature.

Eosinophilic gastroenteritis is an inflammatory disease of unknown etiology characterized by infiltration of the gastrointestinal tract with eosinophilic leukocytes, accompanied by varying abdominal symptoms and usually by peripheral blood eosinophilia. We report our experience with six pediatric cases presenting to the Cleveland Clinic Foundation over the past eight years. Unusual findings in our patients included ascitic fluid without eosinophilia and eosinophilic pericarditis (one patient), and eosinophilic cholecystitis (one patient). Endoscopic examination and biopsy helped to establish the diagnosis in all patients. Bone marrow aspiration supported the diagnosis by demonstrating eosinophilia and identifying reactivation of the disease, even in cases without peripheral eosinophilia. All six patients responded promptly to prednisone. Diagnosis is challenging and eosinophilic gastroenteritis may be more common than is recognized. This series of cases significantly expands the spectrum of the disease in children, and documents the usefulness of diagnostic endoscopy in this condition.

Adolescent

A simple method of generating variable T1 contrast images using temporally reordered phase encoding.

A rapid method of generating T1 images by means of an inversion pulse followed by a fast low-angle imaging experiment is presented. The T1 contrast is manipulated by a temporal reordering of the phase-encoding gradient, resulting in an almost completely free choice of T1 contrast, without any extra restriction on the size of the data acquisition matrix. The intrinsic rapidity of the sequence renders it insensitive to motion artifacts and lends itself to multipoint T1 calculations. The method is particularly well suited to high-field imaging.

Animals

Variable excitation angle AFP pulses.

RF pulses employing the principle of adiabatic fast passage are finding increasing application with surface coils. A small modification to existing AFP pulses that allows the excitation angle to be chosen largely independently of B1 strength is described here. Rapid 3D imaging applications of such pulses are presented.

Diagnostic Imaging

Projective Fourier angiography.

The Fourier imaging of flow is discussed, and the limitations of imaging time, spatial and velocity resolution, imposed on this technique when applied in conjunction with ECG synchronization are examined. It is argued that this method is best used in projective format, and in vivo examples are presented. The relative velocity spectrum obtained is largely system independent, and quantification of velocity is implicit in the Fourier technique.

Angiography