Biomedical subjects

Robert C Molthen

Publications and source records attributed to Robert C Molthen.

7 recordsLinked to original sources

PubMed2006

A simple, inexpensive, and effective light- carrying laryngoscopic blade for orotracheal intubation of rats.

The research paradigm of using large laboratory animals, in which oroendotracheal intubations are relatively easy, is shifting toward the use of small animals, such as rodents, in which oropharyngeal access is limited, the arytenoid cartilage cycles are faster, and the glottis is much smaller. The considerable growth recently seen in preclinical imaging studies is accompanied by an increased number of rats and mice requiring in vivo intubation for airway management. Tracheal access is important for ventilation, administration of inhaled anesthetics, instillation of drugs or imaging agents, and maintenance of airway patency to reduce mortality during and after operations. I fashioned a light-carrying laryngoscopic blade (laryngoscope) from readily available acrylic-polymethyl methacrylate tubing and used it to perform rapid, effective tracheal intubation in rats. The laryngoscope design and intubation techniques are presented.

Animals↗

PubMed2006

99mTc-labeled C2A domain of synaptotagmin I as a target-specific molecular probe for noninvasive imaging of acute myocardial infarction.

UNLABELLED: The exposure of phosphatidylserine (PtdS) is a common molecular marker for both apoptosis and necrosis and enables the simultaneous detection of these distinct modes of cell death. Our aim was to develop a radiotracer based on the PtdS-binding activity of the C2A domain of synaptotagmin I and assess 99mTc-C2A-GST (GST is glutathione S-transferase) using a reperfused acute myocardial infarction (AMI) rat model. METHODS: The binding of C2A-GST toward apoptosis and necrosis was validated in vitro. After labeling with 99mTc via 2-iminothiolane thiolation, radiochemical purity and radiostability were tested. Pharmacokinetics and biodistribution were studied in healthy rats. The uptake of 99mTc-C2A-GST within the area at risk was quantified by direct gamma-counting, whereas nonspecific accumulation was estimated using inactivated 99mTc-C2A-GST. In vivo planar imaging of AMI in rats was performed on a gamma-camera using a parallel-hole collimator. Radioactivity uptake was investigated by region-of-interest analysis, and postmortem tetrazolium staining versus autoradiography. RESULTS: Fluorescently labeled and radiolabeled C2A-GST bound both apoptotic and necrotic cells. 99mTc-C2A-GST had a radiochemical purity of >98% and remained stable. After intravenous injection, the uptake in the liver and kidneys was significant. For 99mTc-C2A-GST, radioactivity uptake in the area at risk reached between 2.40 and 2.63 %ID/g (%ID/g is percentage injected dose per gram) within 30 min and remained plateaued for at least 3 h. In comparison, with the inactivated tracer the radioactivity reached 1.06 +/- 0.49 %ID/g at 30 min, followed by washout to 0.52 +/- 0.23 %ID/g. In 7 of 7 rats, the infarct was clearly identifiable as focal uptake in planar images. At 3 h after injection, the infarct-to-lung ratios were 2.48 +/- 0.27, 1.29 +/- 0.09, and 1.46 +/- 0.04 for acute-infarct rats with (99m)Tc-C2A-GST, sham-operated rats with (99m)Tc-C2A-GST, and acute-infarct rats with 99mTc-C2A-GST-NHS (NHS is N-hydroxy succinimide), respectively. The distribution of radioactivity was confirmed by autoradiography and histology. CONCLUSION: The C2A domain of synaptotagmin I labeled with fluorochromes or a radioisotope binds to both apoptotic and necrotic cells. Ex vivo and in vivo data indicate that, because of elevated vascular permeability, both specific binding and passive leakage contribute to the accumulation of the radiotracer in the area at risk. However, the latter component alone is insufficient to achieve detectable target-to-background ratios with in vivo planar imaging.

Animals↗

PubMed2005

Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries.

Restenosis resulting from neointimal hyperplasia (NH) limits the effectiveness of intravascular stents. Rates of restenosis vary with stent geometry, but whether stents affect spatial and temporal distributions of wall shear stress (WSS) in vivo is unknown. We tested the hypothesis that alterations in spatial WSS after stent implantation predict sites of NH in rabbit iliac arteries. Antegrade iliac artery stent implantation was performed under angiography, and blood flow was measured before casting 14 or 21 days after implantation. Iliac artery blood flow domains were obtained from three-dimensional microfocal X-ray computed tomography imaging and reconstruction of the arterial casts. Indexes of WSS were determined using three-dimensional computational fluid dynamics. Vascular histology was unchanged proximal and distal to the stent. Time-dependent NH was localized within the stented region and was greatest in regions exposed to low WSS and acute elevations in spatial WSS gradients. The lowest values of WSS spatially localized to the stented area of a theoretical artery progressively increased after 14 and 21 days as NH occurred within these regions. This NH abolished spatial disparity in distributions of WSS. The results suggest that stents may introduce spatial alterations in WSS that modulate NH in vivo.

Animals↗

PubMed2005

Microfocal X-ray computed tomography post-processing operations for optimizing reconstruction volumes of stented arteries during 3D computational fluid dynamics modeling.

Restenosis caused by neointimal hyperplasia (NH) remains an important clinical problem after stent implantation. Restenosis varies with stent geometry, and idealized computational fluid dynamics (CFD) models have indicated that geometric properties of the implanted stent may differentially influence NH. However, 3D studies capturing the in vivo flow domain within stented vessels have not been conducted at a resolution sufficient to detect subtle alterations in vascular geometry caused by the stent and the subsequent temporal development of NH. We present the details and limitations of a series of post-processing operations used in conjunction with microfocal X-ray CT imaging and reconstruction to generate geometrically accurate flow domains within the localized region of a stent several weeks after implantation. Microfocal X-ray CT reconstruction volumes were subjected to an automated program to perform arterial thresholding, spatial orientation, and surface smoothing of stented and unstented rabbit iliac arteries several weeks after antegrade implantation. A transfer function was obtained for the current post-processing methodology containing reconstructed 16 mm stents implanted into rabbit iliac arteries for up to 21 days after implantation and resolved at circumferential and axial resolutions of 32 and 50 microm, respectively. The results indicate that the techniques presented are sufficient to resolve distributions of WSS with 80% accuracy in segments containing 16 surface perturbations over a 16 mm stented region. These methods will be used to test the hypothesis that reductions in normalized wall shear stress (WSS) and increases in the spatial disparity of WSS immediately after stent implantation may spatially correlate with the temporal development of NH within the stented region.

Angiography↗

PubMed2004

Quantitative models of the rat pulmonary arterial tree morphometry applied to hypoxia-induced arterial remodeling.

Little is known about the constituent hemodynamic consequences of structural changes that occur in the pulmonary arteries during the onset and progression of pulmonary arterial remodeling. Many disease processes are known to be responsible for vascular remodeling that leads to pulmonary arterial hypertension, cor pulmonale, and death. Histology has been the primary tool for evaluating pulmonary remodeling, but it does not provide information on intact vascular structure or the vessel mechanical properties. This study is an extension of our previous work in which we developed an alternative imaging technique to evaluate pulmonary arterial structure. The lungs from Sprague-Dawley rats were removed, perfusion analysis was performed on the isolated lungs, and then an X-ray contrast agent was used to fill the arterial network for imaging. The lungs were scanned over a range of intravascular pressures by volumetric micro-computed tomography, and the arterial morphometry was mapped and measured in the reconstructed isotropic volumes. A quantitative assessment of hemodynamic, structural, and biomechanical differences between rats exposed for 21 days to hypoxia (10% O(2)) or normoxia (21.0% O(2)) was performed. One metric, the normalized distensibility of the arteries, is significantly (P < 0.001) larger [0.025 +/- 0.0011 (SE) mmHg(-1)] (n = 9) in normoxic rats compared with hypoxic [0.015 +/- 0.00077 (SE) mmHg(-1)] (n = 9). The results of the study show that these models can be applied to the Sprague-Dawley rat data and, specifically, can be used to differentiate between the hypoxic and the control groups.

Animals↗

PubMed2004

Effect of ventilation rate on instilled surfactant distribution in the pulmonary airways of rats.

Liquid can be instilled into the pulmonary airways during medical procedures such as surfactant replacement therapy, partial liquid ventilation, and pulmonary drug delivery. For all cases, understanding the dynamics of liquid distribution in the lung will increase the efficacy of treatment. A recently developed imaging technique for the study of real-time liquid transport dynamics in the pulmonary airways was used to investigate the effect of respiratory rate on the distribution of an instilled liquid, surfactant, in a rat lung. Twelve excised rat lungs were suspended vertically, and a single bolus (0.05 ml) of exogenous surfactant (Survanta, Ross Laboratories, Columbus, OH) mixed with radiopaque tracer was instilled as a plug into the trachea. The lungs were ventilated with a 4-ml tidal volume for 20 breaths at one of two respiratory rates: 20 or 60 breaths/min. The motion of radiodense surfactant was imaged at 30 frames/s with a microfocal X-ray source and an image intensifier. Dynamics of surfactant distribution were quantified for each image by use of distribution statistics and a homogeneity index. We found that the liquid distribution depended on the time to liquid plug rupture, which depends on ventilation rate. At 20 breaths/min, liquid was localized in the gravity-dependent region of the lung. At 60 breaths/min, the liquid coated the airways, providing a more vertically uniform liquid distribution.

Algorithms↗

PubMed2004

Dynamic small animal lung imaging via a postacquisition respiratory gating technique using micro-cone beam computed tomography.

RATIONALE AND OBJECTIVES: Micro computed tomography is an important tool for small animal imaging. On many occasions, it is desirable to image lungs in a live instead of postmortem small animal to perform a pulmonary physiology study. Because the lungs are moving, gating with respect to the ventilatory phase has to be performed to reduce motion artifacts. Precapture ventilation gating may be difficult to achieve in some situations, which motivates us to propose and implement a simple postacquisition gating method. MATERIALS AND METHODS: Rats were used as the subjects in this study. A sequence of low-dose projection images were acquired at 30 frames per second for each view angle. During each capture sequence the rat undergoes multiple ventilation cycles. Using the sequence of projection images, an automated region of interest algorithm, based on integrated grayscale intensity, tracts the ventilatory phase of the lungs. In the processing of an image sequence, multiple projection images are identified at a particular phase and averaged to improve the signal-to-noise ratio. The resulting averaged projection images from different view angles are input to a Feldkamp cone-beam algorithm reconstruction algorithm to obtain isotropic image volumes. RESULTS: Reconstructions with reduced movement artifacts are obtained. In the gated reconstruction, registration of the bone is much better, the edge of the lung is clearly defined, and structures within the lung parenchyma are better resolved. Also, different phases of a breathing cycle can be reconstructed from one single tomographic scan by the proposed gating method. CONCLUSION: A postacquisition gating method using the phase information encoded in the 2-dimensional cone beam projections is proposed. This method is simple to implement and does not require additional experimental set-up to monitor the respiration. It may find applications in lung tumor detection, dynamic pulmonary physiology studies, and the respiratory systems modeling. Minimal motion artifact data sets improve qualitative and quantitative analysis techniques that are useful in physiologic studies of pulmonary structure and function.

Animals↗