Biomedical subjects

L W Hedlund

Publications and source records attributed to L W Hedlund.

At least 55 records · Page 3Linked to original sources

PubMed1995

Detection of bromobenzene-induced hepatocellular necrosis using magnetic resonance microscopy.

The authors used magnetic resonance (MR) microscopy to assess hepatic tissue damage induced by bromobenzene both in living rats and in fixed rat liver tissues. Experiments were conducted at 7 Tesla on three groups of Fisher rats treated with bromobenzene at a single dose of 68, 135, and 269 mg/kg, respectively. Optical microscopy of hematoxylin and eosin stained sections showed liver damage only at the highest dose, whereas with MR microscopy, tissue alterations were detected at all three doses both in vivo and ex vivo. The contrast mechanism of the superior sensitivity of MR microscopy is believed to be related to the changes in local diffusion coefficients that accompany cellular degeneration and death, although other contrast mechanisms may also be involved. The superior sensitivity of MR microscopy, as demonstrated in this study, has many implications for potential use of MR techniques to perform in vivo histology.

Animals↗

PubMed1994

Studies on bromobenzene-induced hepatotoxicity using in vivo MR microscopy with surgically implanted RF coils.

Using surgically implanted RF coils at 300 MHz, three-dimensional microscopic MR images of rat liver were obtained in vivo to follow the development of pathology induced by bromobenzene exposure. Formalin fixed specimens of liver from these animals were also imaged using in vitro MR microscopy, followed by conventional optical microscopy. All MR images were acquired using a spin-warp pulse sequence with TR = 950 ms and TE = 23 ms. The in vivo images were reconstructed as 256(2) x 32 arrays with a voxel size of (50 microns)2 x 219 microns, while the in vitro images were reconstructed as 256(2) x 128 arrays, giving an isotropic resolution at (39 microns)3. Based on results from six animals, we have found in all animals exposed to bromobenzene, image intensity decreased in specific hepatic tissue regions. These regions were well correlated to low signal intensity areas observed in in vitro MR images at higher resolution. Conventional optical microscopy indicated that the low signal intensity regions corresponded to areas of necrosis. The decrease in signal intensity is consistent with increased local diffusion coefficients as a result of necrosis. This study demonstrates that MR microscopy with implanted RF coils can be successfully used to follow tissue pathological changes in living tissues.

Animals↗

PubMed1994

Three dimensional magnetic resonance microangiography of rat neurovasculature.

Techniques are described to perform three dimensional (3D) MR microangiography. We have combined the use of a blood pool agent (Gd-DTPA-complexed with bovine serum albumin), three dimensional Fourier encoding, careful animal stabilization, and volume rendering to permit imaging with voxels of 60 x 60 x 60 microns. 3DFT encoding has been performed at 7.1 T with very large arrays (256 x 512 x 512). Interactive volume rendering allows a number of unique display opportunities that effectively exploit these isotropic 3D arrays.

Animals↗

PubMed1994

Magnetic resonance microscopy of the rat carotid artery at 300 megahertz.

RATIONALE AND OBJECTIVES: Magnetic resonance microscopy (MRM) has evolved from a technical curiosity to a tool with which researchers can study important disease models. But MRM is not simply an extension of clinical magnetic resonance imaging. In this article, the unique adaptations of MRM required in the study of carotid artery disease are outlined. The techniques of MRM are integrated into a specific model of carotid artery disease in the rat to allow in vivo studies of vascular wall thickening after removal of the vascular endothelium. METHODS: Imaging was performed at 300 MHz in 250-gm Sprague-Dawley rats using surgically implanted radiofrequency coils to localize the region of interest and to provide an increase in the signal-to-noise ratio over that of volume or surface coils. A three-dimensional Fourier encoding sequence was modified with flow-dephasing gradients to minimize signal and artifacts from moving blood. RESULTS: In vivo images were acquired with spatial resolution of 25 x 25 x 400 microns and signal-to-noise ratio more than sufficient to define the morphology of the vascular wall. Significant changes in the intensity and distribution of signal were visible in the area surrounding the vessel after angioplasty. CONCLUSIONS: Signal-to-noise improvements from surgically implanted coils coupled to a three-dimensional radiofrequency-refocused sequence with flow-dephasing gradients were sufficient to define the wall of the carotid artery. The diffusion-weighted pulse sequence detects signal changes in the area surrounding the vessel after angioplasty. The MRM techniques described and the contrast observed allow us, for the first time to follow in vivo the early stage of developing atherosclerosis in the vessel wall and closely surrounding tissue.

Angioplasty, Balloon↗

PubMed1993

MR microscopy of the rat lung using projection reconstruction.

Projection reconstruction has been implemented with self-refocused selection pulses on a small bore, 2.0 T MR microscope, to allow imaging of lung parenchyma. Scan synchronous ventilation and cardiac gating have been integrated with the sequence to minimize motion artifacts. A systematic survey of the pulse sequence parameters has been undertaken in conjunction with the biological gating parameters to optimize resolution and signal-to-noise (SNR). The resulting projection images with effective echo time of < 300 microseconds allow definition of lung parenchyma with an SNR improvement of approximately 15 x over a more conventional 2DFT short echo gradient sequence.

Animals↗

PubMed1993

Magnetic resonance imaging of blood flow with a phase subtraction technique. In vitro and in vivo validation.

RATIONALE AND OBJECTIVES: One promising approach to flow quantification uses the velocity-dependent phase change of moving protons. A velocity-encoding phase subtraction technique was used to measure the velocity and flow rate of fluid flow in a phantom and blood flow in volunteers. METHODS: In a model, the authors measured constant flow velocities from 0.1 to 270.0 cm/second with an accuracy (95% confidence intervals) of +/- 12.5 cm/second. There was a linear relationship between the magnetic resonance imaging (MRI) measurement and the actual value (r2 = .99; P = .0001). RESULTS: Measuring mean pulsatile flow from 125 to 1,900 mL/minute, the accuracy of the MRI pulsatile flow measurements (95% confidence intervals) was +/- 70 mL/minute. There was a linear relationship between the MRI pulsatile flow measurement and the actual value (r2 = .99; P = .0001). In 10 normal volunteers, the authors tested the technique in vivo, quantitating flow rates in the pulmonary artery and the aorta. The average difference between the two measurements was 5%. In vivo carotid flow waveforms obtained with MRI agreed well with the shape of corresponding ultrasound Doppler waveforms. CONCLUSIONS: Velocity-encoding phase subtraction MRI bears potential clinical use for the evaluation of blood flow. Potential applications would be in the determination of arterial blood flow to parenchymal organs, the detection and quantification of intra- and extra-cardiac shunts, and the rapid determination of cardiac output and stroke volume.

Adult↗

PubMed1993

Clot-blood contrast in fast gradient-echo magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Contrast between clot and blood in magnetic resonance imaging (MRI) at 1.5T using fast gradient-echo pulse sequences (fast GRE), with 8 ms < TR < 20 mseconds was studied both in vitro and in clinical human deep venous thrombosis (DVT) to assess whether good contrast could be obtained at such short repetition times and at clinically relevant flow rates. METHODS: In vitro studies used an apparatus that contained flowing MnCl2[aq] (water adjusted with manganese chloride to have T1, T2 similar to blood) and an immobilized clot (T1, T2 similar to those in DVT) for flow velocities between 0 and 16.5 cm/sec. Seven patients with DVT were imaged with the fast GRE sequences to observe the clot-blood contrast in vivo. RESULTS: Peak contrast-to-noise ratio (CNR) was achieved using flip angles between 20 degrees and 40 degrees (increasing with flow velocity) with or without radiofrequency "spoiling," consistent with a natural spoiling effect of flow. The CNR between MnCI2[aq] and clot decreased less than 10% as TR was reduced 56% from 18 mseconds to 8 mseconds (30 degrees flip angle). In four patients with nonocclusive DVT, fast GRE imaging provided good contrast while in occlusive cases (three patients) the contrast was not as good as conventional GRE sequences with longer TR values (TR = 33 mseconds). CONCLUSION: A fast GRE sequence with TR = 8 mseconds, TE = 3 mseconds, and a flip angle = 40 degrees is a promising approach to speeding up the detection of nonocclusive clinical DVT.

Blood↗

PubMed1993

Histology by magnetic resonance microscopy.

Magnetic resonance microscopy (MRM) has advanced from a technical challenge to a practical tool in a wide range of basic sciences. This article focuses on the use of MRM as a tool for histological studies. The technical challenges of limited signal to noise have been overcome by improved radio-frequency (rf) coil design and 3DFT encoding with large arrays. Resolution limits imposed by motion in in vivo studies have been overcome by improved physiologic monitoring and control and projection encoding. Integration of technologies now permits routine studies in vivo down to 50 microns. MRM has also been applied to in vitro studies of fixed tissues where absence of motion allows studies down to 10 microns. The nondestructive nature of the technique allows repeated studies of the same sample, retrospective studies through any arbitrary plane, registered studies using different contrast mechanisms, and examination of valuable specimens. The many and unique proton contrasts provided by MRM, i.e., T1, T2, and diffusion weighting, permit direct examination of the state of water in tissues, something not possible with other microscopic techniques. Finally, the inherent three-dimensional nature of MRM allows acquisition of perfectly registered isotropic 3D arrays that, when displayed with appropriate visualization tools, provide new perspectives to histologic examination. The technology of MRM continues to develop rapidly. New pulse sequences are reducing acquisition times. New computer architectures allow larger arrays. A new class of superconducting rf probe has increased the signal to noise ratio by 10 times. These developments promise routine use of MRM in histology studies with resolution to 1 micron in the near future.

Animals↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1990

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↗

PubMed1990

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↗