Biomedical subjects

G Allan Johnson

Publications and source records attributed to G Allan Johnson.

36 records · Page 2Linked to original sources

PubMed2003

Optimization of eight-element multi-detector row helical CT technology for evaluation of the abdomen.

PURPOSE: To evaluate protocols for abdominal imaging with an eight-element multi-detector row computed tomographic (CT) scanner. MATERIALS AND METHODS: An eight-element helical CT scanner was used to acquire data in two phantoms with four-element (pitch, 0.75 and 1.5; section thickness, 1.25, 2.5, and 5.0 mm) and eight-element (pitch, 0.625, 0.875, 1.35 and 1.675; section thickness, 1.25 and 2.5 mm) protocols. One phantom was used for low-contrast detectability and streak artifact; the other, for high-contrast performance. Protocols included near constant radiation dose (140 kV and varied tube current, confirmed by using the above protocols to scan a dedicated radiation dose phantom). Data were analyzed by three blinded readers for streak artifacts, contrast-to-noise ratio, and z-axis resolution (contrast-transfer function). Statistical analysis included studentized range tests. RESULTS: Contrast-to-noise ratios for four and eight elements were not consistently different. Qualitative evaluation for streak artifacts revealed fewer artifacts for all eight-element 1.25-mm-thick section protocols, as compared with eight-element 2.5-mm protocols. All eight-element 2.5-mm protocols except that with 27.0 mm per rotation had fewer streak artifacts than did four-element protocols (P =.02-.04). Contrast-transfer functions along the z axis for eight-element protocols were better than those for four-element protocols, demonstrating improved z-axis resolution (P <.05). CONCLUSION: Images acquired at eight sections per rotation demonstrated no sacrifice of contrast-to-noise ratio, improved z-axis resolution, and fewer streak artifacts, even when radiation dose was similar to that for four-element CT.

Artifacts↗

PubMed2003

Myocardial volume and organization are changed by failure of addition of secondary heart field myocardium to the cardiac outflow tract.

Cardiac neural crest ablation results in primary myocardial dysfunction and failure of the secondary heart field to add the definitive myocardium to the cardiac outflow tract. The current study was undertaken to understand the changes in myocardial characteristics in the heart tube, including volume, proliferation, and cell size when the myocardium from the secondary heart field fails to be added to the primary heart tube. We used magnetic resonance and confocal microscopy to determine that the volume of myocardium in the looped heart was dramatically reduced and the compact layer of myocardium was thinner after neural crest ablation, especially in the outflow tract and ventricular regions. Proliferation measured by 5-bromo-2'-deoxyuridine incorporation was elevated at only one stage during looping, cell death was normal and myocardial cell size was increased. Taken together, these results indicate that there are fewer myocytes in the heart. By incubation day 8 when the heart would have normally completed septation, the anterior (ventral) wall of the right ventricle and right ventricular outflow tract was significantly thinner in the neural crest-ablated embryos than normal, but the thickness of the compact myocardium was normal in all other regions of the heart. The decreased volume and number of myocardial cells in the heart tube after neural crest ablation most likely reflects the amount of myocardium added by the secondary heart field.

Animals↗

PubMed2003

Measurement of regional lung function in rats using hyperpolarized 3helium dynamic MRI.

Dynamic regional lung function was investigated in rats using a radial acquisition cine (RA-CINE) pulse sequence together with hyperpolarized (HP) (3)He gas delivered by a constant flow ventilator. Based on regional differences in the behavior of inspired air, the lung was conceptually divided into two regions (the major airways and the peripheral airspace) for purposes of functional analysis. To measure regional function in the major airways, a large RF flip angle (24 degrees) was applied to reduce (3)He magnetization in the peripheral airspace, and signal intensity (SI) was normalized with the projected airway diameter to estimate local airflow. Higher normalized signal intensity was observed in the left branch airway as compared to the right branch airway. To determine regional function in the peripheral airspace, a small RF flip angle (6 degrees) was used. Incremental increases of peripheral SI in successive lung images were consistent with the increase in lung volume. A new "skipping" scanning strategy using dummy frames allows a trade-off between the number of frames acquired for dynamic information, the RF flip angle, and the penetration depth of (3)He magnetization into the lung. This work provides a novel approach to simultaneously assess dynamic regional function and morphology.

Animals↗

PubMed2003

Improved preparation of chick embryonic samples for magnetic resonance microscopy.

Previous work demonstrated the power of three-dimensional (3D) magnetic resonance microscopy (MRM) to follow complicated morphologic development in the embryonic cardiovascular system. In this study we describe a new dual-contrast method for specimen preparation that combines perfusion fixation and immersion in fixative with macro- and small molecular gadolinium agents to provide enhanced definition of both the heart wall and chamber. MRM was performed at 9.4 T with image resolutions of 25, 31, and 50 microm isotropic voxels for three stages of chick embryos (day 4, day 5.5, and day 9), and compared to histological sections of the same embryos. The results show considerable improvement of image quality over previous efforts, with better signal-to-noise ratio (SNR) and contrast between the cardiac chamber and myocardial wall. Excellent correlation was shown between the MRM images and histological sections. Thus, 3D high-resolution MRM in combination with the dual-contrast technique is useful for acquiring quantitative 3D morphologic data regarding heart development.

Animals↗

PubMed2002

Imaging inflammation: direct visualization of perivascular cuffing in EAE by magnetic resonance microscopy.

PURPOSE: To determine if the architectural features revealed by magnetic resonance microscopy (MRM) allow one to detect microscopic abnormalities associated with neuroinflammation in fixed brain sections from animals with experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). MATERIALS AND METHODS: Imaging was performed at the Center for In Vivo Microscopy (CIVM) using a 9.4-Tesla, 89-mm bore, superconducting magnet with actively shielded gradients capable of 850 mT/m. A number of MR contrasts and spatial resolutions were explored. RESULTS: The assessment of EAE brain showed that it is possible to visualize perivascular cuffing in vitro by MRM on three-dimensional T1 proton stains. CONCLUSION: Inflammatory cell infiltration is a prerequisite for the development of lesions in EAE and MS. Thus, the ability to directly detect individual perivascular cuffs of inflammation may provide a useful means of monitoring the time course of inflammatory events, as conventional histopathological scoring of perivascular cuffs is utilized, but in the absence of sectioning and staining.

Animals↗

PubMed2002

Magnetic resonance histology for morphologic phenotyping.

Magnetic resonance histology (MRH) images of the whole mouse have been acquired at 100-micron isotropic resolution at 2.0 T with image arrays of 256 x 256 x 1024. Higher resolution (50 x 50 x 50 microns) of limited volumes has been acquired at 7.1T with image arrays of 512 x 512 x 512. Even higher resolution images (20 x 20 x 20 microns) of isolated organs have been acquired at 9.4 T. The volume resolution represents an increase of 625000 x over conventional clinical MRI. The technological basis is summarized that will allow basic scientists to begin using MRH as a routine method for morphologcic phenotyping of the mouse. MRH promises four unique attributes over conventional histology: 1). MRH is non-destructive; 2). MRH exploits the unique contrast mechanisms that have made MRI so successful clinically; 3). MRH is 3-dimensional; and 4). the data are inherently digital. We demonstrate the utility in morphologic phenotyping a whole C57BL/6J mouse.

Animals↗

PubMed2002

Fiber-optic stethoscope: a cardiac monitoring and gating system for magnetic resonance microscopy.

A fundamental problem associated with using the conventional electrocardiograph (ECG) to monitor a subject's cardiac activity during magnetic resonance imaging (MRI) is the distortion of the ECG due to electromagnetic interference. This problem is particularly pronounced in MR microscopy (MRI of small animals at microscopic resolutions (< 0.03 mm(3))) because the strong, rapidly-switching magnetic field gradients induce artifacts in the animal's ECG that often mimic electrophysiologic activity, impairing the use of the ECG for cardiac monitoring and gating purposes. The fiber-optic stethoscope system offers a novel approach to measuring cardiac activity that, unlike the ECG, is immune to electromagnetic effects. The fiber-optic stethoscope is perorally inserted into the esophagus of small animals to optically detect pulsatile compression of the esophageal wall. The optical system is shown to provide a robust cardiac monitoring and gating signal in rats and mice during routine cardiac MR microscopy.

Animals↗

PubMed2002

MRI of the lungs using hyperpolarized noble gases.

The nuclear spin polarization of the noble gas isotopes (3)He and (129)Xe can be increased using optical pumping methods by four to five orders of magnitude. This extraordinary gain in polarization translates directly into a gain in signal strength for MRI. The new technology of hyperpolarized (HP) gas MRI holds enormous potential for enhancing sensitivity and contrast in pulmonary imaging. This review outlines the physics underlying the optical pumping process, imaging strategies coping with the nonequilibrium polarization, and effects of the alveolar microstructure on relaxation and diffusion of the noble gases. It presents recent progress in HP gas MRI and applications ranging from MR microscopy of airspaces to imaging pulmonary function in patients and suggests potential directions for future developments.

Animals↗

PubMed2002

Mechanical ventilation for imaging the small animal lung.

This review emphasizes some of the challenges and benefits of in vivo imaging of the small animal lung. Because mechanical ventilation plays a key role in high-quality, high-resolution imaging of the small animal lung, the article focuses particularly on the problems of ventilation support, control of breathing motion and lung volume, and imaging during different phases of the breathing cycle. Solutions for these problems are discussed primarily in relation to magnetic resonance imaging, both conventional proton imaging and the newer, hyperpolarized helium imaging of pulmonary airways. Examples of applications of these imaging solutions to normal and diseased lung are illustrated in the rat and guinea pig. Although difficult to perform, pulmonary imaging in the small animal can be a valuable source of information not only for the normal lung, but also for the lung challenged by disease.

Anatomy, Cross-Sectional↗

PubMed2002

Liver: single breath-hold dynamic subtraction CT with multi-detector row helical technology feasibility study.

Fifty-two patients with known or suspected hypervascular malignancy were examined to determine the technical feasibility of performing single-breath-hold dynamic subtraction computed tomography (CT) of the liver with multi-detector row helical CT. The precontrast and hepatic arterial CT scans, which were acquired during the same breath hold, were subtracted. The mean liver-to-muscle contrast ratio on the precontrast, hepatic arterial, and subtracted images was 1.3, 1.4, and 2.3, respectively. In 13 patients with lesions, the subtracted images showed a 2.5-fold increase in mean lesion contrast compared with the hepatic arterial CT scans.

Adult↗

PubMed2002

Morphologic phenotyping with MR microscopy: the visible mouse.

A method for rapid morphologic phenotyping is demonstrated by using magnetic resonance microscopy. Whole fixed C57BL/6J mice were imaged at 110-microm isotropic resolution; limited volumes of the intact specimen, at 50-microm isotropic resolution; and isolated organs, at 25-microm isotropic resolution. The three-dimensional imaging technique was applied to uricase knockout mice to demonstrate the method for the evaluation of morphologic phenotype.

Animals↗

PubMed2001

Diabetes insipidus in uricase-deficient mice: a model for evaluating therapy with poly(ethylene glycol)-modified uricase.

Uricase-deficient mice develop uric acid nephropathy, with high mortality rates before weaning. Urate excretion was quantitated and renal function was better defined in this study, to facilitate the use of these mice as a model for evaluating poly(ethylene glycol)-modified recombinant mammalian uricases (PEG-uricase) as a potential therapy for gout and uric acid nephropathy. The uric acid/creatinine ratio in the urine of uricase-deficient mice ranges from 10 to >30; on a weight basis, these mice excrete 20- to 40-fold more urate than do human subjects. These mice consistently develop a severe defect in renal concentrating ability, resulting in an approximately sixfold greater urine volume and a fivefold greater fluid requirement, compared with normal mice. This nephrogenic diabetes insipidus leads to dehydration and death of nursing mice but, with adequate water replacement, high urine flow protects adults from progressive renal damage. Treatment of uricase-deficient mice with PEG-uricase markedly reduced urate levels and, when initiated before weaning, preserved the renal architecture (as evaluated by magnetic resonance micros-copy) and prevented the loss of renal concentrating function. PEG-uricase was far more effective and less immunogenic than unmodified uricase. Retention of uricase in most mammals and its loss in humans and some other primates may reflect the evolution of renal function under different environmental conditions. PEG-uricase could provide an effective therapy for uric acid nephropathy and refractory gout in human patients.

Animals↗

PubMed2000

MR-compatible ventilator for small animals: computer-controlled ventilation for proton and noble gas imaging.

We describe an MR-compatible ventilator that is computer controlled to generate a variety of breathing patterns, to minimize image degrading effects of breathing motion, and to support delivery of gas anesthesia and experimental inhalational gases. A key feature of this ventilator is the breathing valve that attaches directly to the endotracheal tube to reduce dead volume and allows independent control of inspiratory and expiratory phases of ventilation. This ventilator has been used in a wide variety of MR and x-ray microscopy studies of small animals, especially for MR imaging the lungs with hyperpolarized gases ((3)He & (129)Xe).

Animals↗

PubMedDate not supplied

Tumor imaging in small animals with a combined micro-CT/micro-DSA system using iodinated conventional and blood pool contrast agents.

X-ray based micro-computed tomography (CT) and micro-digital subtraction angiography (DSA) are important non-invasive imaging modalities for following tumorogenesis in small animals. To exploit these imaging capabilities further, the two modalities were combined into a single system to provide both morphological and functional data from the same tumor in a single imaging session. The system is described and examples are given of imaging implanted fibrosarcoma tumors in rats using two types of contrast media: (a) a new generation of blood pool contrast agent containing iodine with a concentration of 130 mg/mL (Fenestratrade mark VC, Alerion Biomedical, San Diego, CA, USA) for micro-CT and (b) a conventional iodinated contrast agent (Isovue(R)-370 mg/mL iodine, trademark of Bracco Diagnostics, Princeton, NJ, USA) for micro-DSA. With the blood pool contrast agent, the 3D vascular architecture is revealed in exquisite detail at 100 microm resolution. Micro-DSA images, in perfect registration with the 3D micro-CT datasets, provide complementary functional information such as mean transit times and relative blood flow through the tumor. This imaging approach could be used to understand tumor angiogenesis better and be the basis for evaluating anti-angiogenic therapies.

Angiography, Digital Subtraction↗

PubMedDate not supplied

Development of a 4-D digital mouse phantom for molecular imaging research.

PURPOSE: We develop a realistic and flexible 4-D digital mouse phantom and investigate its usefulness in molecular imaging research. METHODS: Organ shapes were modeled with non-uniform rational B-spline (NURBS) surfaces based on high-resolution 3-D magnetic resonance microscopy (MRM) data. Cardiac and respiratory motions were modeled based on gated magnetic resonance imaging (MRI) data obtained from normal mice. Pilot simulation studies in single-photon emission computed tomography (SPECT) and X-ray computed tomography (CT) were performed to demonstrate the utility of the phantom. RESULTS: NURBS are an efficient and flexible way to accurately model the anatomy and cardiac and respiratory motions for a realistic 4-D digital mouse phantom. The phantom is capable of producing realistic molecular imaging data from which imaging devices and techniques can be evaluated. CONCLUSION: The phantom provides a unique and useful tool in molecular imaging research. It can be used in the development of new imaging instrumentation, image acquisition strategies, and image processing and reconstruction methods.

Animals↗

PubMedDate not supplied

Applications of magnetic resonance microscopy.

Magnetic resonance imaging (MRI) has enjoyed enormous clinical success since the first demonstration of the method more than 30 years ago. An increasing number of pharmaceutical manufacturers seeking new biomarkers for assessing drug efficacy and toxicity are turning to MRI. A specific application of MRI promises to revolutionize pathology for the basic scientist in the same way MRI has forever altered the standard of care in the clinical domain. More specifically, this application is the use of magnetic resonance microscopy (MRM) in conjunction with new staining methodologies that now make MRM routinely available to the widest range of investigators.

Animals↗

PubMedDate not supplied

Contribution of magnetic resonance microscopy in the 12-week neurotoxicity evaluation of carbonyl sulfide in Fischer 344 rats.

In this carbonyl sulfide (COS) study, magnetic resonance microscopy (MRM) and detailed light microscopic evaluation effectively functioned in parallel to assure that the distribution and degree of pathology in the brain was accurately represented. MRM is a powerful imaging modality that allows for excellent identification of neuroanatomical structures coupled with the ability to acquire 200 or more cross-sectional images of the brain, and the ability to display them in multiple planes. F344 rats were exposed to 200-600 ppm COS for up to 12 weeks. Prior to MRM, rats were anesthetized and cardiac perfused with McDowell Trump's fixative containing a gadolinium MR contrast medium. Fixed specimens were scanned at the Duke Center for In Vivo Microscopy on a 9.4 Tesla magnetic resonance system adapted explicitly for microscopic imaging. An advantage of MRM in this study was the ability to identify lesions in rats that appeared clinically normal prior to sacrifice and the opportunity to identify lesions in areas of the brain which would not be included in conventional studies. Other advantages include the ability to examine the brain in multiple planes (transverse, dorsal, sagittal) and obtain and save the MRM images in a digital format that allows for postexperimental data processing and manipulation. MRM images were correlated with neuroanatomical and neuropathological findings. All suspected MRM images were compared to corresponding H&E slides. An important aspect of this study was that MRM was critical in defining our strategy for sectioning the brain, and for designing mechanistic studies (cytochrome oxidase evaluations) and functional assessments (electrophysiology studies) on specifically targeted anatomical sites following COS exposure.

Administration, Inhalation↗

PubMedDate not supplied

4-D micro-CT of the mouse heart.

PURPOSE: Demonstrate noninvasive imaging methods for in vivo characterization of cardiac structure and function in mice using a micro-CT system that provides high photon fluence rate and integrated motion control. MATERIALS AND METHODS: Simultaneous cardiac- and respiratory-gated micro-CT was performed in C57BL/6 mice during constant intravenous infusion of a conventional iodinated contrast agent (Isovue-370), and after a single intravenous injection of a blood pool contrast agent (Fenestra VC). Multiple phases of the cardiac cycle were reconstructed with contrast to noise and spatial resolution sufficient for quantitative assessment of cardiac function. RESULTS: Contrast enhancement with Isovue-370 increased over time with a maximum of approximately 500 HU (aorta) and 900 HU (kidney cortex). Fenestra VC provided more constant enhancement over 3 hr, with maximum enhancement of approximately 620 HU (aorta) and approximately 90 HU (kidney cortex). The maximum enhancement difference between blood and myocardium in the heart was approximately 250 HU for Isovue-370 and approximately 500 HU for Fenestra VC. In mice with Fenestra VC, volumetric measurements of the left ventricle were performed and cardiac function was estimated by ejection fraction, stroke volume, and cardiac output. CONCLUSION: Image quality with Fenestra VC was sufficient for morphological and functional studies required for a standardized method of cardiac phenotyping of the mouse.

Animals↗