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L W Hedlund

Publications and source records attributed to L W Hedlund.

At least 37 records · Page 2Linked to original sources
PubMed1998

Magnetic resonance microscopy and histopathology: comparative approach of bromobenzene-induced hepatotoxicity in the rat.

The development of magnetic resonance (MR) microscopy has provided new approaches to histology and histopathology. Recent work has shown the promise of increased sensitivity in animal models of chemically induced hepatotoxicity. However, the field is so new that there is little experience to relate changes seen in MR micrographs to the more traditional optical images stained with hematoxylin and eosin. This work compares the sensitivity and reproducibility of MR microscopy with conventional histopathology in detecting bromobenzene-induced hepatotoxicity in the rat. A time-course study was undertaken to provide a range of histopathologies. Specimens were studied at 24, 48, 72, and 96 hours after exposure to 10% of the median lethal dose of bromobenzene. Using 4 animals per group (a total of 32 rats) added statistical significance to the study and defined a range of interanimal variability over 96 hours. This work shows that MR microscopy, besides being nondestructive and three-dimensional, is at least as sensitive as conventional hematoxylin-eosin staining in detecting bromobenzene-induced centrilobular lesions and recovery of the hepatocellular architecture in the rat. This study further suggests that, as we begin to understand the underlying mechanisms of contrast in MR histology, MR may, in fact, supply even higher specificity than more traditional studies: variations were observed in MR images of treated livers at a given time point that could be not be differentiated based on the grading of necrosis and inflammation on hematoxylin-eosin-stained sections.

Animals↗
PubMed1998

MR microscopy of lung airways with hyperpolarized 3He.

A technique using hyperpolarized (HP) 3He to image the small airways of the lung by using moderate flip angles and a short scanning period during early inspiration is demonstrated. Flip angles (alpha) ranging from 10-90 degrees were used in guinea pig experiments with scanning during the entire inspiration period. A second series acquired data throughout a short window of the ventilatory cycle with alpha = 45 degrees. The success of the animal studies has motivated implementation of similar imaging techniques in the clinical arena. Human studies involved imaging over the total inspiration period with alpha approximately 10 degrees. The first series of guinea pig experiments demonstrated that larger flip angles (50-90 degrees) destroy the magnetization before it reaches the smaller airways. At moderate flip angles (20-40 degrees), airway branching down to the fourth generation was apparent. Fifth-order branchings were seen in the images of the second series. The trachea down to fourth generation pulmonary airway branching, along with some distal air spaces, was seen in the human lung images.

Animals↗
PubMed1998

Time-course imaging of rat embryos in utero with magnetic resonance microscopy.

Magnetic resonance (MR) microscopy was used to noninvasively investigate the development of live rat embryos in utero. The difficulty in making sequential observations of a developing mammalian embryo has frustrated developmental biologists for many years. Most current technologies analyze normal and abnormal development by observing end point phenotypes (in fixed specimens) rather than investigating the live embryo. MR microscopy was adapted to allow rat litters to be scanned three times each (at 1- to 3-day intervals) and has produced images of live developing embryos. It was demonstrated that repeated anesthesia and imaging protocols produced no gross malformations in the rat pups that were subsequently delivered and observed. Three-dimensional projection encoding with phase rewinders produced isotropic [256(3)] image data sets in about 30 minutes with excellent tissue contrast arising from steady-state effects in the amniotic fluid.

Animals↗
PubMed1998

Hyperpolarized 3He NMR lineshape measurements in the live guinea pig lung.

Spatially localized lineshapes of hyperpolarized (HP) 3He in guinea pig lungs have been measured in vivo. Three different axial slice locations, each containing different compositions of airway sizes and orientations, were studied. Gas peaks from major bronchi (2 ppm) and alveoli (-2 ppm) were distinguished. The gas phase spectra show structural features that are a result of frequency shifts caused by bulk magnetic susceptibility. For a given slice, the spectral lineshapes reflect the airway composition within the slice location, according to theory. The peak assignments given here also agree with previous studies done by Wagshul et al. with HP 129Xe. At each of the slice locations, data were acquired during two phases of the breathing cycle, resulting in a relative frequency shift of approximately 0.3 ppm in the superior slices. Spectra obtained over a number of breaths show the dynamics of the gas buildup in the lung and provide further evidence supporting the peak assignments.

Animals↗
PubMed1998

Quantification of myocardial perfusion by MRI after coronary occlusion.

The objectives of this study were to define the relationship between the first order constant of Gd-DTPA transfer (K1) and the myocardial blood flow (MBF) at rest and to compare it with an equivalent relationship obtained for positron emission tomography (PET). In a canine model of permanent coronary occlusion (n = 4), myocardial and blood time concentration curves obtained by 13N-ammonia PET and Gd-DTPA-enhanced MRI were fitted by a one-compartment model to determine K1. A linear relationship was observed between MRI-derived K1 and MBF measured by microspheres (K1 = 0.88 x flow -0.015, R = 0.95), which compares favorably with the equivalent relationship derived from PET (K1 = 0.74 x flow +0.16, R = 0.88). The results of this preliminary study suggest that, at rest and distal to a permanently occluded coronary artery, myocardial perfusion quantification by MRI is possible and can challenge PET.

Animals↗
PubMed1998

Functional MRI of the rat somatosensory cortex: effects of hyperventilation.

Functional mapping of the rat somatosensory cortex was performed with T2*-sensitized MRI using a forepaw electrical stimulation model in alpha-chloralose-anesthetized rats at 7 T under both normocapnia and mild hyperventilation-induced hypocapnia. A highly localized activation area, consistent with the known somatosensory cortical region, was detected in all seven animals studied during hypocapnia and in five of the same animals during normocapnia. Quantitatively, hypocapnia was found to significantly increase both the size of the fMRI activation area (3.4 +/- 0.6 mm2 versus 1.5 +/- 0.6 mm2 in normocapnia, mean +/- standard error, n = 7, P < 0.03) and the average fMRI signal intensity increase (3.4 +/- 0.6% versus 2.7 +/- 0.4%, n = 5, P < 0.05). The increased sensitivity of fMRI to functional activation may reflect a widened arterial-venous oxygenation difference resulting from an increased effective oxygen extraction during hyperventilation. The dependence of the fMRI response on the ventilation state underscores the need to control for physiological parameters in animal fMRI studies.

Afferent Pathways↗
PubMed1998

Signal dynamics in magnetic resonance imaging of the lung with hyperpolarized noble gases.

The nonequilibrium bulk magnetic moment of hyperpolarized (HP) noble gases generated by optical pumping has unique characteristics. Based on the Bloch equations, a model was developed describing the signal dynamics of HP gases used in magnetic resonance imaging (MRI) of the lung with special consideration to the breathing cycle. Experimental verification included extensive investigations with HP 3He and 129Xe during both inspiration and held breath in live guinea pigs. Radial acquisition was used to investigate the view variations with a temporal resolution of 5 ms. Agreement between theoretical predictions and in vivo results was excellent. Additionally, information about effects from noble gas diffusion and spin-lattice relaxation was obtained. In vivo results for T1 were 28.8 +/- 1.8 s for 3He and 31.3 +/- 1.8 s for 129Xe. Comparison with in vitro data indicated that relaxation in the pulmonary gas space is dominated by dipolar coupling with molecular oxygen. The results provide a quantitative basis for optimizing pulse sequence design in HP gas MRI of the lung.

Animals↗
PubMed1998

Measuring the progression of foreign-body reaction to silicone implants using in vivo MR microscopy.

We used in vivo magnetic resonance (MR) microscopy to follow the growth of fibrous capsule as a foreign body reaction to silicone implants in rats. Anesthetized rats were imaged 1, 7, 14, and 28 days after silicone-coated MR imaging coils were sutured to their neck muscles. On the twenty-eighth day, rats were sacrificed and coils and adjacent tissues were removed en bloc and fixed in formalin, reimaged with MR, and sectioned for conventional histology. Three-dimensional (3-D) spin-echo [3DFT] acquisition gave in-plane resolution of 32 x 32 microns in vivo and 16 x 16 microns ex vivo. All MR images showed a diffuse band of elevated signal intensity between the silicone of the coil and adjacent tissue. The border of the hyperintense band was thin and not well defined at seven days post-implantation. From 7-28 days, the band showed relatively homogeneous signal intensity and its thickness increased 44% on the rectus muscle side and 78% on the subcutaneous side. The capsule thickness determined either by MR in vivo and ex vivo microscopy or conventional histology was not significantly different, and there was a significant correlation between thickness measurements among those methods. MR in vivo microscopy provides sufficient resolution and spatial information to serially evaluate the growth of the foreign body fibrous capsule over time, thus achieving greater accuracy and consistency in measurements.

Animals↗
PubMed1997

Dynamics of magnetization in hyperpolarized gas MRI of the lung.

The magnetization in hyperpolarized gas (HP) MRI is generated by laser polarization that is independent of the magnet and imaging process. As a consequence, there is no equilibrium magnetization during the image acquisition. The competing processes of gas inflow and depolarization of the spins lead to large changes in signal as one samples k-space. A model is developed of dynamic changes in polarization of hyperpolarized 3He during infusion and in vivo imaging of the lung and verified experimentally in a live guinea pig. Projection encoding is used to measure the view-to-view variation with temporal resolution < 4 ms. Large excitation angles effectively sample the magnetization in the early stages of inflow, highlighting larger airways, while smaller excitation angles produce images of the more distal spaces. The work provides a basis for pulse sequences designed to effectively exploit HP MRI in the lung.

Animals↗
PubMed1997

MR microimaging of the lung using volume projection encoding.

Radial acquisition (RA) techniques have been extended to produce isotropic, three-dimensional images of lung in live laboratory animals at spatial resolution down to 0.013 mm3 with a signal-to-noise ratio of 30:1. The pulse sequence and reconstruction algorithm have been adapted to allow acquisition of image matrices of up to 256(3) in less than 15 min. Scan-synchronous ventilation has been incorporated to limit breathing motion artifacts. The imaging sequence permits randomizing and/or discarding selected views to minimize the consequences of breathing motion. The signal in lung parenchyma was measured as a function of flip angle (alpha) for different repetition times and found to follow the predictions for which there is an optimum excitation (Ernst) angle. A single T1 relaxation value of 780 +/- 54 ms fits all data from six guinea pigs at 2.0 T. This T1 value parameterizes the signal and allows for a priori optimization, such as calculation of the Ernst angle appropriate for lung imaging.

Animals↗
PubMed1997

MRI quantitative myocardial perfusion with compartmental analysis: a rest and stress study.

K1 (first-order transfer constant from arterial plasma to myocardium for Gd-DTPA) and Vd (distribution volume of Gd-DTPA in myocardium) were measured in vivo in a canine model (n = 5) using MRI-derived myocardial perfusion curves and a compartmental model. Perfusion curves were obtained after a bolus injection of Gd-DTPA (0.04 mM/kg) with an inversion-prepared fast gradient echo sequence. Myocardium and blood signal intensity were converted to a concentration of Gd-DTPA, according to a model appropriate for short (<1 s) interimage intervals characteristic of cardiac-triggered acquisitions. Before dipyridamole-induced stress, K1 and Vd, obtained from the fit of the MRI-derived perfusion curves, were 6.2 +/- 1.4 (mHz) and 17.5 +/- 4.2%, respectively. After dipyridamole infusion, a K1 increase of a factor of 2.82 +/- 0.72 was measured (P = 0.003). No change was observed in Vd (P = 0.98). These results suggest that the K1 increase after dipyridamole reflects a flow-related effect that can be useful to quantify the MRI-derived perfusion curves.

Animals↗
PubMed1997

Automated feedback control of body temperature for small animal studies with MR microscopy.

A temperature control system consisting of a thermistor, signal processor, and computer algorithm was developed for magnetic resonance (MR) microscopy of small live animals. With control of body temperature within +/- 0.2 degree C of the set point, heart rate is stabilized and, in turn, repetition time (TR) during cardiac-gated studies is less variable. Thus, image quality and resolution are improved.

Animals↗
PubMed1996

A new in vivo method for quantitative analysis of stroke lesions using diffusion-weighted magnetic resonance microscopy.

Using three-dimensional diffusion-weighted MR microscopy and a rat model of focal cerebral ischemia, we evaluated the statistical characteristics of two parameters: absolute stroke volumes and change in stroke volumes over 6 h of middle cerebral artery (MCA) occlusion. In all rats, the absolute stroke volumes increased linearly over the 6-h MCA occlusion time period. On average, stroke volume growth rate was 2.1 +/- 0.5%/h. Sample size power analysis of our data demonstrated that to demonstrate a 10% reduction of the 6-h volumes, sample size per group would require 29 animals (these calculations are based on alpha = 0.05, beta = 0.20 using normal approximation). A similar 30% reduction of stroke volume at 6 h poststroke (from approximately equal to 200 to 140 mm3) would, in our "slope model," translate into a reduction of stroke growth rate from the normal + 11.25 mm3/h (150 to 200 mm3 over 4 h) to 7 mm3/h (150 to 178 mm3 over 4 h); power analysis in this case demonstrated that sample size is reduced to 15 animals per group (these calculations are based on alpha = 0.05, beta = 0.20 using normal approximation). We conclude that from a statistical standpoint our study demonstrates that stroke growth rate might be a more suitable parameter for evaluating the effect of treatment in both clinical and experimental stroke trials.

Animals↗
PubMed1996

In vivo He-3 MR images of guinea pig lungs.

The authors imaged the lungs of live guinea pigs with hyperpolarized (HP) helium-3 as a magnetic resonance (MR) signal source. HP He-3 gas produced through spin exchange with rubidium metal vapor was delivered through an MR-compatible, small-animal ventilator. Two- and three-dimensional lung images acquired with ventilation-gated, radial k-space sampling showed complete ventilation of both lungs. All images were of high quality, demonstrating that HP He-3 allows high-signal-intensity MR imaging in living systems.

Animals↗
PubMed1995

MR imaging with hyperpolarized 3He gas.

Magnetic resonance images of the lungs of a guinea pig have been produced using hyperpolarized helium as the source of the MR signal. The resulting images are not yet sufficiently optimized to reveal fine structural detail within the lung, but the spectacular signal from this normally signal-deficient organ system offers great promise for eventual in vivo imaging experiments. Fast 2D and 3D GRASS sequences with very small flip angles were employed to conserve the norenewable longitudinal magnetization. We discuss various unique features associated with performing MRI with hyperpolarized gases, such as the selection of the noble gas species, polarization technique, and constraints on the MR pulse sequence.

Animals↗
PubMed1995

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↗