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Biomedical subjects

L W Hedlund

Publications and source records attributed to L W Hedlund.

At least 19 recordsLinked to original sources

MR microscopy of the rat carotid artery after balloon injury by using an implanted imaging coil.

Neointimal hyperplasia after angioplasty was followed in vivo in rats by using MR microscopy and surgically implanted RF imaging coils. By using an inductively coupled pick-up coil, the arteries were imaged 4 days before and 3, 7, and 14 days after angioplasty with a 3DFT spin echo sequence. Eight of 10 angioplastied rats showed moderate to severe stensois based MR measures of lumen diameter reduction from baseline images. There was a good correlation between total wall thickness between MR and hematoxylin and eosin (H&E)-stained sections obtained on the last day. Arteries in the intact and sham groups remained unchanged from baseline measurements. Because this imaging technique examines the artery under in vivo conditions of arterial pressure and flow, it promises to be a useful tool for evaluating pharmacological and mechanical methods of reducing the incidence of vascular stenosis.

Angioplasty, Balloon

Surface coil imaging of rat spine at 7.0 T.

An inductively coupled surface coil for imaging the rat spine at 7 T is described. This planar circular probe was made from microwave substrate to limit the size of the coil and to minimize the magnetic susceptibility. The surface coil was used as a single transmit/receive coil and as a receive-only coil with a birdcage body coil for excitation. The signal-to-noise ratio (SNR) of the probe was compared to a 5-cm birdcage coil and exceeded the birdcage coil's SNR by three to six times at superficial structures. The main advantages of the probe are an improved SNR for superficial structures and a simple design and use. Images with 50 x 50 x 500 micron voxels were obtained of the rat spine with excellent anatomical detail.

Animals

Mechanism of detection of acute cerebral ischemia in rats by diffusion-weighted magnetic resonance microscopy.

BACKGROUND AND PURPOSE: The aim of this study was to measure apparent diffusion coefficients in rat brain tissue exposed to ouabain, glutamate, and N-methyl-D-aspartate and to compare them with apparent diffusion coefficients found in acute cerebral ischemia. METHODS: The apparent diffusion coefficient was measured using magnetic resonance microscopy in four groups of Sprague-Dawley rats after occlusion of the right middle cerebral artery and ipsilateral common carotid artery (n = 7), after ouabain exposure (n = 6), during glutamate exposure (n = 7), or during N-methyl-D-aspartate exposure (n = 3). Ouabain, glutamate, and N-methyl-D-aspartate were applied via an intracerebrally implanted microdialysis membrane. RESULTS: Three hours after the induction of focal cerebral ischemia, a 33% reduction in the apparent diffusion coefficient was observed in the right dorsolateral corpus striatum and olfactory cortex. After ouabain exposure, reductions in the apparent diffusion coefficient were observed within a 1,500-microns radius of the microdialysis membrane. Quantitative analysis revealed that apparent diffusion coefficient values in ischemic and ouabain-exposed tissue fell within the same range. Glutamate and N-methyl-D-aspartate reduced the brain tissue apparent diffusion coefficient by 35% and 40%, respectively. CONCLUSIONS: On the basis of these findings, we conclude that ischemia-induced apparent diffusion coefficient reductions are likely caused by a shift of extracellular to intracellular water.

Acute Disease

Detection of acute avascular necrosis of the femoral head in dogs: dynamic contrast-enhanced MR imaging vs spin-echo and STIR sequences.

OBJECTIVE: Spin-echo MR imaging has been shown to be highly sensitive in the detection of avascular necrosis. Very early avascular necrosis can, however, appear normal on MR images. We compared dynamic contrast-enhanced MR imaging with conventional spin-echo and short Tl inversion-recovery (STIR) sequences for detecting acute osteonecrosis in an animal model. MATERIALS AND METHODS: Avascular necrosis was induced unilaterally in the femoral heads of five dogs that were imaged with a 1.5-T system within 3 hr of devascularization. After standard T1-weighted, T2-weighted, and STIR images, gradient-recalled echo images, 28/5 (TR/TE) with a 45 degrees flip angle, were obtained at 6-sec intervals for 90 sec synchronous with the IV administration of 0.2 mmol of gadoteridol per kilogram of body weight at a rate of 2 ml/sec via an automated injector. Two animals were reimaged after 7 days. RESULTS: Spin-echo and STIR images did not show any acute changes in the ischemic femoral heads. In contrast, significant differences were present in the enhancement profiles of the marrow spaces in the normal and ischemic femoral heads (p = .005). Normal marrow was characterized by rapid enhancement, with an average signal intensity increase of 83% peaking at 36 sec; no measurable enhancement was seen in the marrow of the ischemic femoral head. Spin-echo images, obtained 7 days after devascularization (n = 2), showed changes characteristic of avascular necrosis. Dynamic contrast-enhanced MR images showed persistent lack of enhancement in the avascular marrow of the ischemic femoral head. A junctional zone, characterized by rapid contrast enhancement in excess of 120% without early washout, was identified at the interface between normal and avascular marrow. CONCLUSION: In this experimental model, dynamic contrast-enhanced MR imaging proved significantly more sensitive than conventional spin-echo and STIR imaging in the detection of acute avascular necrosis.

Acute Disease

Pre- and postmortem diffusion coefficients in rat neural and muscle tissues.

Pulsed gradient diffusion-weighted spin-echo images (7 to 11 gradient strengths) were obtained in a coronal slice through the midbrain for five normal adult white rats before and after sacrifice in a 2-T CSI system with air temperature control. The pulse sequence was cardiac gated and respiratory synchronized in order to minimize motion artifacts (Tr greater than 2 s. Te = 30 ms). Diffusion coefficients reflecting several tissue compartments (D*) in brain and muscle were calculated and referenced to simultaneously imaged tubes of water. In the living animals, brain cortical matter had a value of D* = (0.82 +/- 0.02) x 10(-3) mm2/s. deeper brain regions had a value of D* = (0.73 +/- 0.02) x 10(-3) mm2/s, and the muscle had a value of D* = (1.4 +/- 0.1) x 10(-3) mm2/s. Postmortem the values in brain dropped by approximately 30%, while remaining constant in muscle. Signal intensity in the spin-echo images for muscle tissue rose by 50% over a 1- to 2-h interval after sacrifice while that of brain tissue remained relatively stable.

Animals

Magnetic resonance microscopy of toxic renal injury induced by bromoethylamine in rats.

The alkylhalide 2-bromoethylamine hydrobromide (BEA) produces renal injury in rats that mimics analgesic-related renal injury in humans. Our purpose was to examine this injury, in vivo in rats, with magnetic resonance (MR) microscopy and correlate MR findings with findings from light microscopy of hematoxylin-eosin-stained sections. Rats (n = 48) were injected intravenously with BEA (150 mg/kg) or saline and imaged with MR 6, 48, and 336 hr later. The spin-spin relaxation time, T2, was measured from the cortex to the papilla. In other rats, we measured regional water content of the kidney. Renal injury was present 48 and 336 hr after BEA dosing based on increased renal organ weights, decreased urine specific gravity, and significant renal lesions (H & E). T2 was elevated in the inner stripe of the outer medulla in injured kidneys at 48 hr. The differences in T2 between cortex and outer medulla were also elevated 48 hr after BEA. In the inner medulla, there were no changes in T2 after BEA treatment. However, in all groups there were significant regional differences in T2. The value of T2 increased from outer to inner medulla and this gradient was directly correlated with water content. Thus, MR microscopy detected damage in the outer medulla after BEA injury but not the damage in the inner medulla. T2 appeared to reflect the water content in the different regions of the medulla. The noninvasive in vivo capability of MR microscopy, with its high sensitivity to tissue water, allows the toxicologist to monitor the progression and regression of toxic insult in the same animal. At present the technology is complicated. The precise and accurate measure of MR-sensitive parameters in live animals at microscopic resolution is difficult. However, as the technology matures, there will be significant improvements providing the toxicologist a unique in vivo tool.

Animals

Evaluation of acute renal failure with magnetic resonance imaging using gradient-echo and Gd-DTPA.

Detection of acute renal failure (ARF) using fast-scan magnetic resonance imaging (MRI) with Gd-DTPA was studied in a dog model. ARF was produced in five dogs by infusion of norepinephrine (0.75 micrograms/kg/min) into the renal arteries for 40 minutes. MRI was performed 1 hour later and compared with baseline (pre-ARF) MRI. There was no significant difference in the ratios of signal intensity-vs.-time curves from 0 to 35 seconds after injection of Gd-DTPA. However, a difference between the outer and inner medulla was significant in the time period of 5 to 20 minutes after Gd-DTPA injection. These later signal intensity differences by fast-scan (gradient-echo) technique may be useful in the evaluation of ARF.

Acute Kidney Injury

Extravascular toxicity of two magnetic resonance contrast agents. Preliminary experience in the rat.

We compared the relative toxicities of standard concentrations of two magnetic resonance imaging (MRI) contrast agents, ionic gadolinium diethylenetriaminepentacetic acid (DTPA) and low-osmolar gadolinium-1, 4, 7 tris (carboxymethyl)-10-(2'-hydroxypropyl)-1, 4, 7, 10 tetra-azacyclododecane (HP-DO3A) with that of the conventional radiographic contrast medium meglumine diatrizoate, when extravasated into the deep dermal tissues of laboratory rats. Gadolinium-DTPA caused moderate necrosis, hemorrhage, and edema which was not statistically different than meglumine diatrizoate. In contrast, gadolinium HP-DO3A was significantly less toxic than meglumine diatrizoate. Additional experience will be needed in order to determine whether these laboratory results will be clinically relevant in humans.

Animals

Cine phase-contrast magnetic resonance imaging for analysis of flow phenomena in experimental aortic dissection.

Using a 1.5 T magnetic resonance imaging (MRI) system, cine phase-contrast and magnitude images were obtained in three phantoms that simulated different anatomic configurations of aortic dissection. The dissection phantoms were made of compliant materials, and pulsatile flow was used in all experiments. Phantoms differed only in the location of the fenestration between the true and false lumens (I: an upstream "entry" only, II: both upstream "entry" and downstream "re-entry," and III: a downstream "entry" only). Flow jets, flap motion, and wave propagation were clearly visualized in cine MR images of each phantom, and quantitatively analyzed with reference to the stimulated cardiac cycle of the pump. Flow in the false lumen was always bidirectional. Upstream and downstream flow waves collided and dispersed within the false lumen. Flow through the false lumen was the same in phantoms I and II, and least in phantom III. The average area of the true lumen was largest in phantom III and smallest in I. Phantom I had the highest overall flow rate in the false lumen and greatest change in false lumen size during the cardiac cycle, while the downstream "entry" phantom had the lowest of both parameters. Flow phenomena in aortic dissections can be studied by cine phase-contrast MRI.

Aortic Dissection

MR imaging of experimental and clinical thrombi at 1.5 T.

We have previously reported that the T1 and T2 of experimental clots at 0.47 T varies considerably depending upon the method used in their preparation. However, these studies, while relevant to midfield imaging, may not reflect accurately the behavior of such thrombi at higher field strengths. Accordingly, we studied the T1 and T2 at 1.5 T of experimental thrombi prepared by several methods and compared these results with the relaxation times of clinical deep venous thrombi measured in situ in patients. The relationship between the T2 values for the different clot preparation methods was different at 1.5 T than at 0.47 T. The combined use of thrombin and epsilon-amino caproic acid produced thrombi with T1 and T2 indistinguishable from clinical deep venous thrombi.

Aminocaproic Acid

Extravascular extravasation of radiographic contrast media. Effects of conventional and low-osmolar agents in the rat thigh.

We compared the damage resulting from intradermal injection of four commonly used radiographic contrast media in laboratory rats. Sixty percent meglumine diatrizoate (Reno M 60) and ioxaglate (Hexabrix) produced significantly more ulceration and crusting on gross inspection and more necrosis, edema, and hemorrhage on histologic evaluation than iopamidol 300 (Isovue) or 0.9% (normal) saline. Thirty percent meglumine diatrizoate (Reno M Dip) had an intermediate toxicity, resulting in significantly more visible swelling and more microscopically detected hemorrhage than iopamidol or saline, but less ulceration/crusting and necrosis than Reno M 60 and ioxaglate. Since the three contrast agents of similar osmolality produced different degrees of tissue damage, our results suggest that factors other than high osmolality are partially responsible for determining the severity of injuries from extravasated contrast media.

Animals

Implanted coil MR microscopy of renal pathology.

Inductively coupled implanted coils have been shown to provide up to a 10-fold increase in signal-to-noise ratio when compared to whole-body imaging of small animals. The current study was designed to extend the implanted coil imaging technique to a rodent model of renal pathology. Resonant radiofrequency (RF) coils were implanted around the left kidney of four rats and inductively coupled from within a birdcage body coil. All images were acquired at 2 T using a T1-weighted spin-echo sequence with TR = 500 ms and TE = 20 ms. In vivo MR microscopy with voxels of 117 x 117 x 2000 microns demonstrated cortex, inner and outer medulla, and major vascular structures on baseline images. Mercuric chloride-induced nephrotoxic acute tubular necrosis (ATN) diminished cortico-medullary contrast at 24 h after dosing with pathologic evaluation demonstrating nephrotoxic changes in the inner cortex. The kidney regained a baseline MR appearance 360 h after dosing and resolution of the damage was confirmed with histology. T1 data were gathered on excised kidneys as an adjunct to the images to help correlate the loss and return of cortico-medullary contrast with the pathology and pathophysiology of nephrotoxic ATN. With implanted RF coils we were able to demonstrate renal pathology and follow its subsequent resolution. Specifically, loss and return of cortico-medullary contrast as a result of nephrotoxic ATN were serially documented in four rats. Such serial in vivo studies performed on single animals should further the use of MR microscopy by minimizing the number of animals required for adequate biostatistics.

Animals

Evaluation of flow through simulated vascular stenoses with gradient echo magnetic resonance imaging.

Magnetic resonance imaging using gradient echo sequences can quickly generate dynamic images of the cardiovascular system. We used a gradient echo sequence (repetition time = 21 milliseconds, echo time = 12 milliseconds, flip angle = 30 degrees) to evaluate how a simulated vascular stenoses affects the signal intensity of flowing fluid. Axial slices were obtained at regular intervals along a plastic tube containing a circular constriction (25%, 51%, or 73% reduction of cross-sectional area). Image data collected at each slice level were used to reconstruct 32 images evenly spaced in time over one cycle of pulsatile flow. Contrast ratios were calculated between signal intensities from tube lumen and surrounding stationary water jacket. Upstream from each stenosis, signal intensity increased during systole and decreased during diastole, paralleling the changes in velocity we measured with a flow probe. However, within the 51% and 73% stenoses and just beyond them, there were consistent decreases in systolic signal intensity. Flow through the 25% constriction had little effect on the signal intensity pattern. These results suggest that the gradient echo pulse sequence may be useful in evaluating disturbed flow associated with vascular stenoses.

Arterial Occlusive Diseases

Fast limited flip angle MR subtraction angiography.

A fast MR angiography method is introduced that is capable of generating difference images of blood vessels in scan times of 10-20 s. This is an order of magnitude faster than many previous methods. The fundamental concept of this approach is to use cardiac gating and acquire several phase encodings at least twice during each cardiac cycle using limited flip angles (LFAs) and repetition times in the 20 to 50 ms range. The encodings acquired during diastole are subtracted from those acquired during systole to generate the difference image. The contrast in the difference image is due both to the influx of unsaturated spins and to the loss of phase coherence of systolic blood moving at high velocity along a magnetic gradient. The systolic peak of the cardiac cycle is determined during reconstruction by shifting the systolic and diastolic "windows" until the difference signal is maximized. Ghost artifacts due to pulsatile flow are eliminated by a phase reordering technique similar in concept to those developed for suppression of breathing artifacts. Arteries in thick slices are successfully imaged and initial in vivo results are presented.

Angiography

Effects of turbulence on signal intensity in gradient echo images.

Although the appearance of laminar vascular flow in magnetic resonance (MR) images has been characterized, there is no general agreement about the effect of turbulent flow on MR signal intensity. This study uses a fast scan gradient echo pulse sequence to evaluate nonpulsatile turbulent flow in two different models. The first model simulated flow in normal vascular structure. It generated nonpulsatile, laminar and turbulent flow in straight, smooth-walled Plexiglas tubes. The second model simulated flow through a vascular stenosis. It generated nonpulsatile, laminar, and turbulent flow through an orifice. Velocities and flow rates ranged from low physiologic to well above the physiologic range (velocity = .3 to 280 cm/second, flow rate from .15 to 40 L/minute). Transition from laminar to turbulent flow was observed with dye streams. Turbulent flow in straight, smooth-walled vessels was not associated with a decrease in MR signal intensity even at the highest velocities and flow rates studied. The transition from laminar to turbulent flow through an orifice is not associated with a decrease in gradient echo signal intensity. As the intensity of the turbulent flow increases, however, there is a threshold above which signal intensity decreases linearly as turbulence increases (r = .97). This study suggests that flow in normal vascular structures should not be associated with decreased signal intensity in gradient echo images. Turbulent flow through areas such as valves, valvular lesions or vascular stenoses, may be associated with a decrease in gradient echo signal intensity.

Blood Flow Velocity

A cardiac phantom and pulsatile flow pump for magnetic resonance imaging studies.

Fast scan magnetic resonance imaging (MRI) acquisitions are a rapid noninvasive means of evaluating the cardiovascular system. Because the appearance of flowing blood is highly variable, the interpretation of these images is sometimes difficult. A nonferromagnetic phantom that could generate lifelike pulsatile flow and also simulate the motions of the beating heart would facilitate image interpretation. This paper describes an MRI-compatible cardiovascular phantom that mimics the motions of the heart and also creates physiologic pulsatile flow. The phantom consists of a ventricle and an air pump that drives it. The pump is connected to the ventricle with seven meters of air hose so that the pump (which has ferromagnetic parts) can be placed outside the magnet room. The ventricle is placed in an airtight Plexiglas cylinder and the pump alternately pressurizes and depressurizes the cylinder, driving fluid in and out of the ventricle. The motions of the ventricular wall simulate the motions of the heart, and the pulsatile flow generated is of physiologic velocities and volumes. This phantom also can be used with other methods of evaluating cardiovascular function, such as MUGAS, angiography, and Doppler, allowing correlation between MRI and other modalities. Finally, the phantom can be used to study almost any aspect of cardiovascular function from pulsatile flow velocity to ventricular studies (ejection fractions, cardiac output, wall motion) and even studies of stenotic or regurgitant valves.

Heart

Magnetic resonance imaging (MRI): a new tool in experimental toxicologic pathology.

Magnetic Resonance Imaging (MRI) is a noninvasive imaging technique that provides multidimensional images of the soft tissues of the body. This imaging technique has proven to be an excellent diagnostic and experimental tool for the detection of pathologic alterations in soft tissues, as well as an adjunct screening method for following the genesis, progression, or regression of chemically induced lesions in the same live animal. Future applications of MRI technology in small animals include MRI microscopy, mapping of vascular or circulatory alterations, measurement of perfusion and diffusion rates of body fluids, and acquisition of cell metabolic states in combination with Nuclear Magnetic Resonance (NMR) spectroscopy, all of which will contribute immensely to the advancement of toxicologic and biomolecular research.

Animals

The fate of inorganic phosphate and pH in regional myocardial ischemia and infarction: a noninvasive 31P NMR study.

To determine the characteristic appearance of phosphorus (31P) nuclear magnetic resonance spectra in acute and chronic myocardial infarction in situ, cardiac-gated depth-resolved surface coil spectroscopy (DRESS) at 1.5 T was used to monitor 31P NMR spectra from localized volumes in the left anterior canine myocardium for up to 5 days following permanent occlusion of the left anterior descending coronary artery. Coronary occlusion initially produced regional ischemia manifested as significant reductions in the phosphocreatine (PCr) to inorganic phosphate (Pi) ratios and intracellular pH (P less than 0.05, Student's t test) in endocardially displaced spectra acquired in periods as short as 50 to 150 s postocclusion. Spectra acquired subsequently revealed either (i) restoration of near-normal phosphate metabolism sometime between 10 and about 50 min postocclusion or (ii) advancing ischemic phosphate metabolism at about an hour postocclusion, and/or (iii) maintenance of depressed PCr/Pi ratios for up to 5 days postocclusion with a return of the apparent pH to near normal values between 6 and 15 h postocclusion. Postmortem examination of animals exhibiting the first type of behavior revealed the existence of coronary collateral vessels. The last type of behavior indicates that Pi remains substantially localized in damaged myocardium for days following infarction. The location and size of infarctions were determined postmortem by staining excised hearts. The smallest infarctions detected by 31P DRESS weighed 4.9 and 7.5 g. The most acidic pH measured in vivo was 5.9 +/- 0.2. Infarctions aged 1/2 day to 5 days were characterized by elevated but broad Pi resonances at 5.1 +/- 0.2 ppm relative to PCr and significantly depressed PCr/Pi ratios (P less than 0.002, Student's t test) relative to preocclusion values. Contamination of Pi resonances by phosphomonoester (PM) components is a significant problem for preocclusion Pi and pH measurements. These results should be applicable to the detection and identification of human myocardial infarction using 31P NMR and DRESS.

Adenosine Triphosphate