New insights into lung diseases using hyperpolarized gas MRI.

Hyperpolarized (HP) gases are a new class of contrast agents that permit to obtain high temporal and spatial resolution magnetic resonance images (MRI) of the lung airspaces. HP gas MRI has become important research tool not only for morphological and functional evaluation of normal pulmonary physiology but also for regional quantification of pathologic changes occurring in several lung diseases. The purpose of this work is to provide an introduction to MRI using HP noble gases, describing both the basic principles of the technique and the new information about lung disease provided by clinical studies with this method. The applications of the technique in normal subjects, smoking related lung disease, asthma, and cystic fibrosis are reviewed.

MR grid-tagging using hyperpolarized helium-3 for regional quantitative assessment of pulmonary biomechanics and ventilation.

A new technique is demonstrated in six healthy human subjects that combines grid-tagging and hyperpolarized helium-3 MRI to assess regional lung biomechanical function and quantitative ventilation. 2D grid-tagging, achieved by applying sinc-modulated RF-pulse trains along the frequency- and phase-encoding directions, was followed by a multislice fast low-angle shot (FLASH)-based acquisition at inspiration and expiration. The displacement vectors, first and second principal strains, and quantitative ventilation were computed, and mean values were calculated for the upper, middle, and lower lung regions. Displacements in the lower region were significantly greater than those in either the middle or upper region (P < 0.005), while there were no significant differences between the three regions for the two principal strains and quantitative ventilation (P = 0.11-0.92). Variations in principal strains and ventilation were greater between subjects than between lung zones within individual subjects. This technique has the potential to provide insight into regional biomechanical alterations of lung function in a variety of lung diseases.

Hyperpolarized 3He lung ventilation imaging with B1-inhomogeneity correction in a single breath-hold scan.

The signal-to-noise ratio (SNR) of hyperpolarized noble gas MR images is sensitive to the flip angle used. Variations in flip angle due to B1-inhomogeneity of the RF coil cause intensity variation artifacts in lung ventilation images which may mask or mimic disease. We show these artifacts can be minimized by using the optimal flip angle and corrected if the local flip angle is known. Hyperpolarized 3He lung images were obtained in ten healthy subjects using both a conventional gradient-echo sequence and a new hybrid pulse sequence designed to simultaneously acquire lung ventilation images and corresponding flip-angle maps in comparable imaging time. Flip-angle maps and corrected images were calculated from the hybrid scan and compared with conventional images. The qualitative theoretical dependence of flip angle on SNR was verified. Ventilation images and flip-angle maps were successfully obtained with the hybrid sequence. Corrections to image intensity calculated from the flip-angle maps appeared reasonable for images acquired using an average flip angle near optimal. Use of the optimal flip angle is crucial to the quality of lung ventilation images. Artifactual intensity variations due to RF-coil inhomogeneity may be identified and potentially corrected using our hybrid sequence.

Dynamic spiral MRI of pulmonary gas flow using hyperpolarized (3)He: preliminary studies in healthy and diseased lungs.

An optimized interleaved-spiral pulse sequence, providing high spatial and temporal resolution, was developed for dynamic imaging of pulmonary ventilation with hyperpolarized (3)He, and tested in healthy volunteers and patients with lung disease. Off-resonance artifacts were minimized by using a short data-sampling period per interleaf, and gradient-fidelity errors were compensated for by using measured k-space trajectories for image reconstruction. A nonsequential acquisition order was implemented to improve image quality during periods of rapid signal change, such as early inspiration. Using a sliding-window reconstruction, cine-movies with a frame rate of 100 images per second were generated. Dynamic images demonstrating minimal susceptibility- and motion-induced artifacts were obtained in sagittal, coronal, and axial orientations. The pulse sequence had the flexibility to image multiple slices almost simultaneously. Our initial experience in healthy volunteers and subjects with lung pathology demonstrated the potential of this new tool for capturing the features of lung gas-flow dynamics.

Hyperpolarized noble gas MR imaging of the lung: potential clinical applications.

Hyperpolarized noble gases are a new class of MR contrast agent. Since the first hyperpolarized gas MR images of the lung were reported, there has been considerable interest in using hyperpolarized gas to obtain high spatial and temporal resolution images of the air spaces of the lung. In addition to static images of lung ventilation, new techniques are being developed using hyperpolarized gas to obtain dynamic, diffusion and oxygen concentration images of the lung. In this article, we review the potential clinical applications of pulmonary hyperpolarized gas MRI and discuss the preliminary findings in a variety of lung diseases. Hyperpolarized gas MRI has the potential to provide a comprehensive morphologic and functional assessment of the lung.

Transforming growth factor beta-coated platinum coils for endovascular treatment of aneurysms: an animal study.

OBJECTIVE: To test the hypothesis that coating platinum coils with transforming growth factor beta (TGFbeta) would improve the cellular proliferation within experimental aneurysms relative to uncoated coils. MATERIALS AND METHODS: Elastase-induced saccular aneurysms were created in 12 New Zealand White rabbits. These aneurysms were embolized with platinum coils, either "control" (unmodified) coils or "test" (coated with TGFbeta) coils. Subjects were killed either 2 weeks (n = 3, control; n = 3, test) or 6 weeks (n = 3, control; n = 3, test) after embolization. Aneurysm tissue was embedded in plastic, sectioned, and stained with hematoxylin and eosin. The thickness of tissue covering the coils at the coil-lumen interface was measured by use of a digital microscope, and was compared between groups by use of the Student's t test (P < or = 0.05). RESULTS: Two-week implantation samples demonstrated mean thickness of tissue overlying TGFbeta-coated coils of 36+/-15 microm and mean thickness of overlying control coils of 3+/-5 microm, indicating significantly thicker tissue growth covering test versus control coils (P = 0.02). Six-week implantation samples demonstrated mean thickness of tissue overlying TGFbeta-coated coils of 86+/-74 microm versus mean thickness overlying control coils of 37+/-6 mu; this difference did not reach statistical significance (P = 0.30). Thickness of tissue covering TGFbeta-coated coils did not change significantly from 2 to 6 weeks (P = 0.31). Tissue thickness over control coils increased significantly between 2 and 6 weeks (P = 0.002). CONCLUSION: TGFbeta-coated platinum coils undergo earlier cellular coverage than standard platinum coils, but differences in coverage between coated and control coils are no longer present at later time points. These data suggest that improvements in intra-aneurysmal cellular proliferation resulting from coil modifications, although significant in the early postembolization phase, may dissipate over time.

Hyperpolarized 3He MR lung ventilation imaging in asthmatics: preliminary findings.

Asthma is a disease characterized by chronic inflammation and reversible obstruction of the small airways resulting in impaired pulmonary ventilation. Hyperpolarized 3He magnetic resonance (MR) lung imaging is a new technology that provides a detailed image of lung ventilation. Hyperpolarized 3He lung imaging was performed in 10 asthmatics and 10 healthy subjects. Seven asthmatics had ventilation defects distributed throughout the lungs compared with none of the normal subjects. These ventilation defects were more numerous and larger in the two symptomatic asthmatics who had abnormal spirometry. Ventilation defects studied over time demonstrated no change in appearance over 30-60 minutes. One asthmatic subject was studied twice in a three-week period and had ventilation defects which resolved and appeared in that time. This same subject was studied before and after bronchodilator therapy, and all ventilation defects resolved after therapy. Hyperpolarized 3He lung imaging can detect the small, reversible ventilation defects that characterize asthma. The ability to visualize lung ventilation offers a direct method of assessing asthmatics and their response to therapy.

Magnetic resonance hysterography and hysterosalpingography using hyperpolarized (3)He: demonstration of feasibility in an animal model.

Assessment of the uterine cavity and patency of the fallopian tubes remains a difficult goal with magnetic resonance imaging (MRI). The purpose of this paper is to describe the development of a new magnetic resonance hysterography (MR-HG) and hysterosalpingography (MR-HSG) technique employing hyperpolarized (3)He. Two-dimensional (2D) and 3D gradient-echo imaging sequences were developed and optimized using a phantom. An optimized sequence was then applied in swine cadavers. J. Magn. Reson. Imaging 2000;12:1009-1013.

MR virtual colonography using hyperpolarized (3)He as an endoluminal contrast agent: demonstration of feasibility.

Hyperpolarized gas MR virtual colonography was performed in plastic phantoms and in the dog colon. (3)He was laser polarized in a prototype commercial system. 2D and 3D gradient echo sequences were used to image the noble gas-filled structures. The hyperpolarized (3)He within the plastic tube and colon lumen produced high signal, providing excellent contrast from the surrounding structures. The virtual colonoscopic analysis of the canine dataset allowed visualization of the colonic features and the colonic wall from inside the colon. (3)He colonoscopy is a novel technique to visualize the colon with MRI with the application of an inert gaseous endoluminal contrast agent.

1999 ARRS Executive Council Award. Creation of saccular aneurysms in the rabbit: a model suitable for testing endovascular devices. American Roentgen Ray Society.

OBJECTIVE: This study developed an animal model of intracranial aneurysms suitable for evaluating emerging endovascular devices for aneurysmal therapy. We characterized the short-, medium-, and long-term attributes of this endovascular technique for saccular aneurysmal creation in the rabbit. MATERIALS AND METHODS: The right common carotid artery was surgically exposed in nine New Zealand white rabbits. Using endovascular techniques, we occluded the origin of the right common carotid artery with a pliable balloon. Elastase was incubated endoluminally in the proximal common carotid artery above the balloon. The common carotid artery was ligated distally. Animals were studied angiographically and sacrificed at 2 weeks (n = 3), 10 weeks (n = 3), and 24 weeks (n = 3) after aneurysm creation. Histology was obtained. RESULTS: Saccular aneurysms formed in eight of the nine rabbits. The aneurysm projected from the apex of an approximately 90 degree curve of the parent vessel, the brachiocephalic artery. Mean aneurysm diameter was 4.5 mm (SD, 1.2 mm), and mean height was 7.5 mm (SD, 1.6 mm). All samples showed thinned elastic lamina and no evidence of inflammation. In four of eight aneurysms, unorganized thrombus was present in the dome of the aneurysm. CONCLUSION: Arterial aneurysms with intact endothelium and deficient elastic lamina were reliably created in an area of high shear stress in New Zealand white rabbits. Three of these aneurysms remained patent for at least 6 months. We found a simple procedure that can be readily applied to the testing of new endovascular devices for a reliable creation of aneurysms in rabbits.

Histologic evaluation of platinum coil embolization in an aneurysm model in rabbits.

PURPOSE: To characterize the histologic response to platinum coil embolization by using a rabbit aneurysm model. MATERIALS AND METHODS: Saccular aneurysms were created in New Zealand White rabbits by using vessel ligation with intraluminal elastase incubation. Aneurysms were subsequently embolized by using platinum coils. Subjects were sacrificed at various intervals up to 12 weeks following coil embolization. The aneurysm cavities and adjacent vessels were embedded in methylmethacrylate, were sectioned, and were stained for histologic examination. RESULTS: Two weeks following coil implantation, aneurysms were filled predominantly with unorganized thrombus. Six weeks following coil implantation, histologic features included complete filling of the aneurysm lumen with either prominent laminated but unorganized thrombus or areas of unorganized thrombus interspersed among areas of cellular infiltration. At 12 weeks following coil implantation, aneurysms were filled with the loosely packed, disordered cells contained within the extracellular matrix. Fibrosis or smooth muscle cell infiltration was not present in any of the 6- or 12-week samples. CONCLUSION: Platinum coils placed into experimental saccular aneurysms in New Zealand White rabbits failed to elicit a fibrotic response. This model can be used for the testing of biologic modifications of platinum coils aimed at increasing intra-aneurysmal fibrosis.

Endovascular creation of an in vivo bifurcation aneurysm model in rabbits.

PURPOSE: To develop a rabbit model of an intracranial bifurcation aneurysm to test new endovascular therapies. MATERIALS AND METHODS: An experimental aneurysm model was created in rabbits by means of endovascular balloon occlusion of the left common carotid artery, which created an aneurysm at the bifurcation formed by the aortic arch and the brachiocephalic trunk. A total of 18 aneurysms were created. In eight rabbits, the aneurysms were incubated with intraluminal elastase to induce degeneration of the elastic laminae. The animals were followed up with angiography for as long as 3 months. The animals were sacrificed at various times, and histologic evaluation of the aneurysm was performed. RESULTS: Ten aneurysms created without elastase infusion were all very small or completely closed at 1-3 months. Six aneurysms created with elastase infusion had long-term patency (two were patent at 1 month and four, at 3 months). The elastase aneurysms had a mean width of 3 mm (range, 2-3.5 mm) and a mean length of 5 mm (range, 3-7 mm). Histologic evaluation revealed destruction of the normal elastin layers, which allowed the artery to become aneurysmal. CONCLUSION: This aneurysm model re-created the hemodynamic forces and size of human cerebral bifurcation aneurysms and maintained the integrity of the endothelium. The creation of the aneurysms was rapid, reliable, and reproducible.

Experimental side-wall aneurysms: a natural history study.

We studied the natural history of canine side-wall experimental aneurysms to determine the incidence of spontaneous aneurysm thrombosis, to serve as control data for future studies focusing on development of aneurysm occlusion devices. Bilateral common carotid artery vein patch aneurysms were surgically created in eight mongrel dogs (20-25 kg). Duplex Doppler sonography was performed at 14 days and angiography between 30 and 210 days following aneurysm creation. Sonography demonstrated patency of 13 (81%) of 16 aneurysms. Patent aneurysms ranged in size from 8 x 10 mm to 14 x 16 mm. Conventional angiography was performed in four dogs approximately 30 days following aneurysm creation; in these four, all of 7 initially patent on sonography remained fully patent. One dog underwent conventional angiography at approximately 60 days following aneurysm creation; both aneurysms in this case remained widely patent. Three dogs underwent conventional angiography at approximately 200 days following aneurysm creation; all 4 aneurysms initially patent on sonography remained fully patent. None of the three aneurysms found to be occluded on sonographs demonstrated spontaneous recanalization. The canine side-wall aneurysm model is a valid tool for testing some aneurysm-occlusion devices, because control aneurysms remain patent indefinitely.

In vitro proliferation and adhesion of basic fibroblast growth factor-producing fibroblasts on platinum coils.

PURPOSE: To evaluate the growth and adhesion characteristics in vitro of genetically modified, basic fibroblast growth factor-producing fibroblasts on platinum detachable coils. MATERIALS AND METHODS: Coils of two sizes were coated with laminin, poly-L-lysine, fibronectin, and type I and type IV collagen and were cultured with basic fibroblast growth factor-secreting fibroblasts. Type I collagen strands were inserted in the lumen of some coils. Cellular proliferation and adherence during passage of coils through microcatheters were studied with both light and scanning electron microscopy. Growth factor concentration in the culture medium was measured. RESULTS: Rapid cellular proliferation was noted on all coated coils except those coated with type IV collagen. Proliferation on uncoated coils was slightly slower than on most coated coils, although confluent cell layers were present on uncoated larger-diameter coils within 48 hours. Cells had a marked propensity to grow between the primary coil windings into the coil lumen, except in coils that contained collagen filaments. Passage through microcatheters caused widespread stripping of cells from the outer surface of coils, especially the uncoated samples. Viable cells remained in the coil lumen. Supernatant contained high concentrations of growth factor. CONCLUSION: Platinum embolic coils are a promising mechanism of cell delivery for stimulation of scar formation or other desirable biologic effects.