Delivery of endothelial cells to balloon-dilated rabbit arteries with use of a local delivery catheter.

PURPOSE: Experiments were performed to determine if a local delivery catheter could deliver endothelial cells that would be retained on the luminal surface of balloon-dilated arteries. MATERIALS AND METHODS: Six New Zealand White rabbits underwent carotid catheterization, arteriography, and balloon angioplasty of an external iliac artery. A local delivery catheter (Dispatch) was then positioned at the site of angioplasty and the 3-mm balloon was inflated. Cultured rabbit endothelial cells (1.26 +/- 0.3 x 10(6) ), previously stained with fluorescent dye PKH26, were delivered to the artery in three infusions separated by 10 minutes. The delivery balloon was deflated and removed 25 minutes after the last delivery. The arteries were then perfusion-fixed in situ at physiologic pressure, removed, and divided into four segments, and the segments were rapidly frozen and cryosectioned. Eight sections from each arterial segment were examined by means of epifluorescence microscopy. The luminal surface of each artery was visually divided into eight sectors of equal length and each sector was assigned a score based on the degree of endothelial coverage (0 = no coverage, 1 = <50% coverage, 2 = >50% coverage). RESULTS: The endothelial coverage score for the six arteries averaged 0.40 +/- 0.46 (SD; range, 0.04-1.24). Areas of each artery receiving scores of 0, 1, and 2 averaged 68%, 25%, and 7%, respectively. Average coverage scores were 0.42, 0.38, 0.51, and 0.28 for individual segments along the length of the artery. CONCLUSIONS: The Dispatch local delivery catheter is able to deliver endothelial cells that adhere to balloon-dilated arteries. Although the magnitude of cellular retention was modest and varied among arteries, the retention along the length of each artery was constant.

Endothelial cell seeding on prosthetic surfaces.

Once thought to be a monolayer of passive cells lining the vasculature, endothelial cells are now known to be important regulators of normal vascular physiology. Unfortunately, these critically important cells are destroyed or removed by interventional and surgical procedures performed to recanalize or bypass vascular obstructions. The loss of these cells contributes to thrombosis and restenosis, the major complications observed after angioplasty, stent deployment, and prosthetic graft implantation. One approach to preventing these complications is the placement of endothelial cells on stents or prosthetic grafts prior to their placement in vivo in the hope that these cells will, after growth and maturation, release the factors necessary to inhibit thrombosis and intimal thickening. The purpose of this review paper is to provide an overview of the physiologic functions of normal and dysfunctional endothelial cells, and to discuss experiments in which endothelial cells have been placed on metallic stents and prosthetic grafts.

Immunolocalization of proliferating cells in the rabbit iliac artery after balloon angioplasty.

PURPOSE: Experiments were performed to characterize the location of proliferating cells in the balloon-dilated rabbit iliac artery. MATERIALS AND METHODS: Balloon angioplasty was performed on the external iliac arteries in each of four rabbits. The arteries were removed 3 days later, frozen, cryosectioned, and immunostained with Ki-67, an antibody that identifies proliferating cells. The sections were then examined to determine the patterns of cell proliferation within the arterial media and the ratio of proliferating to nonproliferating cells. RESULTS: Of the 31 arterial cross-sections examined, cell proliferation was circumferential in five (16%), and focal in 26 (84%). Of the 86 foci of proliferation examined within the 31 cross-sections, proliferation was localized to the inner media in 30 (35%), to the outer media in four (5%), and was transmural in 52 (60%). The internal elastica lamina (IEL) appeared normal at 22 foci (26%), but appeared stretched or torn at 64 (74%). Proliferation was usually confined to the inner media at foci having no IEL injury (18 of 22; 82%), but was most often transmural where the IEL was stretched or torn (49 of 64; 77%). The ratio of proliferating to nonproliferating cells, which averaged 0.31 +/- .20, was greater (P < .01) in areas with IEL injury than in areas without IEL injury. CONCLUSION: These results suggest that angioplasty-induced cell proliferation is typically focal rather than circumferential and is associated with stretching or tearing of the IEL.

Imaging vascular thrombosis with 99mTc-labeled fibrin alpha-chain peptide.

UNLABELLED: An agent that permits scintigraphic detection of chronic deep venous thrombosis (DVT) or pulmonary embolism (PE) would be a welcome addition to the armamentarium of nuclear medicine. Because fibrin is the integral part of each clot, old or fresh, we hypothesized that a 99mTc-labeled fibrin alpha-chain N-terminal peptide, Gly-Pro-Arg-Pro-Pro, that binds to the C-terminal portion of the gamma-chain of fibrin can detect DVT and PE. METHODS: The peptide was modified to Gly-Pro-Arg-Pro-Pro-Aba-Gly-Gly-(D)-Ala-Gly to permit efficient binding of 99mTc (99mTc-TP 850). The stability of the peptide was examined in vitro as well as in vivo. The ability of the agent to bind to rabbit, dog, and human fibrin and to inhibit adenosine diphosphate-induced platelet aggregation was examined. Blood clearance and 3-h tissue distribution were studied. DVT was induced in 8 rabbits using a stimulating electrode and in 2 rabbits by inserting a thrombin-soaked suture. PE was induced in 6 additional rabbits by introducing tantalum-impregnated blood clots into the right atrium, and the rabbits were radiographed to locate the emboli. 99mTc-TP 850 was then injected through a lateral ear vein, and each rabbit was imaged for up to 3 h. The rabbits were then killed, the heart and lungs were dissected and radiographed and the clots were harvested so that clot-to-blood radioactivity ratios could be determined. RESULTS: The peptide analog permitted efficient incorporation of 99mTc, which was stable in vitro and in vivo. The blood clearance was biphasic, with an alpha phase half-life of approximately 4 min (20%) and a beta phase half-life of approximately 13 min (88%). The mean binding of 99mTc-TP 850 to human, dog, and rabbit fibrin was 46% +/- 2%, 60% +/- 3%, and 56% +/- 2.5%, respectively, and the inhibitory concentration of 50% for dog and rabbit platelet aggregation was 236 pm and 167 pm, respectively. All clots, including 24-h-old pulmonary emboli, were delineated. The radioactivity associated with clots varied from 0.01 to 0.09 %ID/g, with clot-to-blood radioactivity ratios ranging from 1.2 to 12.0. However, 48-h-old pulmonary emboli had lysed and were seen neither by radiography nor by scintigraphy. CONCLUSION: A fibrin alpha-chain, N-terminal peptide that binds to the C-terminal portion of the gamma-chain of fibrin has been modified and labeled with 99mTc. The resultant peptide is stable in vitro and in vivo; binds to human, dog, and rabbit fibrin in large quantities; and inhibits platelet aggregation. The peptide clears rapidly from the blood and delineates experimental DVT and PE in rabbits. This agent is worthy of further investigation.

Use of endothelial cells containing superparamagnetic microspheres to improve endothelial cell delivery to arterial surfaces after angioplasty.

PURPOSE: The purpose of this study was to determine if the luminal surface of balloon-dilated arteries can be re-endothelialized circumferentially with use of normal endothelial cells (ECs) and superparamagnetic microsphere-containing endothelial cells (MagECs) to cover gravity-dependent and independent arterial surfaces, respectively. MATERIALS AND METHODS: MagECs were obtained after phagocytosis of albumin-coated superparamagnetic polystyrene microspheres by rabbit microvascular ECs. The effect of microsphere internalization on cell adhesion was determined in vitro by comparing ECs and MagECs in terms of time courses of adhesion to fibronectin and cell retention after exposure to a shear stress. In vivo re-endothelialization was performed by delivering fluorescently labeled ECs and MagECs to a balloon-dilated artery with a double-balloon catheter, placing a magnet over the artery, and rotating the rabbit axially. Endoluminal coverage of arterial cross-sections was estimated by epifluorescence microscopy. RESULTS: Under the influence of gravity, in vitro cell adhesion to fibronectin after 5, 10, and 15 minutes was similar for the ECs (34%, 74%, and 70%) and MagECs (40%, 56%, and 93%). In vitro cell retention after exposure to a shear stress (25 dynes/cm2) was greater (P < .05) for ECs than for MagECs (82% vs 69%). Use of ECs plus MagECs in vivo resulted in cell delivery that was nearly circumferential. CONCLUSIONS: Delivery of a mixture of ECs and MagECs in combination with animal rotation and a magnetic field provide nearly circumferential delivery of ECs to the luminal surface of balloon-dilated arteries. The presence of superparamagnetic microspheres in cells does not impede cell adhesion but does decrease cell retention after exposure to a fluid shear.

Resistance of freshly adherent endothelial cells to detachment by shear stress is matrix and time dependent.

PURPOSE: The placement of endothelial cells on the surfaces of arteries immediately after vascular interventions has the potential to limit restenosis by inhibiting intimal thickening and by stimulating arterial enlargement. Because such re-endothelialization is dependent on rapid formation of strong endothelial cell-matrix interactions, experiments were performed to identify the extracellular matrix that provided endothelial cells with the greatest resistance to detachment by a shear stress in the least amount of time. MATERIALS AND METHODS: Rabbit microvascular endothelial cells were plated onto glass slides coated with collagen, laminin, vitronectin, or fibronectin. After allowing 5-45 minutes for cell adhesion, each slide was placed in a parallel plate chamber, and the number of cells present before and after exposure of the cells to shear stresses (1-25 dynes/cm2) were counted. RESULTS: Endothelial cell retention to the matrix-coated slides was time and matrix dependent. The percentages of endothelial cells retained after adhesion times of 5, 15, 30, and 45 minutes followed by exposure to 15 dynes/cm2 were 9%, 20%, 32%*, and 38%* for collagen; 7%, 20%, 36%*, and 49%* for laminin; 35%, 47%, 62%, and 76%* for vitronectin; and 64%, 58%, 71%, and 78% for fibronectin, respectively (*P < .05 versus 5 minutes adhesion). Similar results were obtained for lower and higher shear stresses, indicating that cell retention was independent of shear stress above 1 dyne/cm2. CONCLUSIONS: The resistance of freshly adherent endothelial cells to detachment by shear stress is matrix- (fibronectin approximately equal to vitronectin > laminin approximately equal to COL) and time-dependent. Fibronectin provided the greatest cell retention in the least amount of time.

1998 SCVIR Gary J. Becker Young Investigator Award. Endovascular repair of arterial pseudoaneurysms with use of a perfusion balloon catheter.

PURPOSE: Pseudoaneurysms represent contained disruption of the arterial wall. Iatrogenic pseudoaneurysms frequently complicate complex endovascular procedures. With use of an animal model, the authors attempted to determine the safety and efficacy of using a perfusion balloon catheter (PBC) to thrombose surgically created pseudoaneurysms. MATERIALS AND METHODS: An in vitro system measured maximum flow volume through a 5-F PBC. Pseudoaneurysms were created in domestic swine with use of a jugular vein patch anastomosed to a femoral arteriotomy. The PBC was inflated across the pseudoaneurysm neck for 30-minute intervals until thrombosis was confirmed by ultrasound. Completion arteriography was performed to evaluate for vascular complications. RESULTS: Maximum flow through the PBC was 62.6 mL/min measured at a constant pressure gradient of 120 mm Hg. Five pseudoaneurysms were created in four animals. The PBC completely thrombosed all five lesions. The mean treatment duration was 129 minutes (+/- 39 minutes SD). No native arterial injury, in situ thrombus, or distal embolization occurred. Partial recanalization of three of the five treated pseudoaneurysms was identified on follow-up arteriography and gross sectioning (n = 2 and n = 1, respectively). CONCLUSION: The PBC safely and effectively thrombosed surgically created pseudoaneurysms. Partial recanalization of treated pseudoaneurysms was demonstrated. Clinical trials are warranted.

Placement of endothelial cells on the luminal surface of denuded arteries in vitro and in vivo.

PURPOSE: Experiments were performed to determine if the percutaneous placement of endothelial cells on denuded arterial surfaces is feasible. MATERIALS AND METHODS: For in vitro adhesion assays, rabbit microvascular endothelial cells were stained with a fluorescent marker and placed on the luminal surface of disks of denuded rabbit aorta. At varying times thereafter, the nonadherent cells were removed, and the adherent cells were quantitated with use of fluorescence microscopy. For in vivo studies, angioplasty was performed on external iliac arteries in five rabbits, and a double-balloon catheter, positioned at the dilatation site, was used to deliver fluorescent rabbit microvascular endothelial cells. Ten minutes (n = 2), 1 hour (n = 2), 1 day (n = 1), or 3 days (n = 1) after cell placement, the number of fluorescent cells remaining on each artery was determined. RESULTS: In vitro rabbit microvascular endothelial cell attachment was (a) serum-dependent, peaking with media containing 25% autologous serum; (b) time-dependent, peaking at 30 minutes; and (c) cell density-dependent. In vivo rabbit microvascular endothelial cell attachment was (a) noncircumferential, (b) appeared to be gravity-dependent, and (c) appeared unchanged over 3 days with respect to number of cells per cross-section and length of artery having endothelium. CONCLUSIONS: Percutaneous delivery of endothelial cells onto denuded arterial surfaces with use of optimal conditions is feasible and these cells remain adherent for at least 3 days.

Mechanisms of vascular preservation by a novel NO donor following rat carotid artery intimal injury.

We studied the effects of a novel organic nitric oxide (NO) donor, 4-hydroxymethyl-furazan-3-carboxylic acid-2-oxide (CAS-1609), in a rat carotid artery intimal injury model. The NO donor, CAS-1609, or its non-NO-donating control compound, 4-hydroxymethyl-furazan-3-carboxylic acid (C-93-4845), was infused intravenously at 30 micrograms/day. Seven days after injury, carotid artery rings contracted only 56 +/- 6 mg to NG-nitro-L-arginine methyl ester in C-93-4845-treated rats, compared with 120 +/- 17 mg in CAS-1609-treated rats (P < 0.02), indicating a preservation of endogenous NO release. Improved responses to the endothelium-dependent dilator, acetylcholine, also occurred in injured arteries treated with CAS-1609. Morphometric analysis of injured carotid arteries given the inactive compound showed marked intimal thickening with an intimal-to-medial ratio (I/M) of 0.76 +/- 0.02, compared with a significantly lower I/M of 0.32 +/- 0.04 (P < 0.01) in injured carotid arteries given CAS-1609. Additionally, CAS-1609 was found to have a concentration-dependent stimulatory effect on cultured rat aortic endothelial cell proliferation (P < 0.01) but and inhibitory effect on platelet-derived growth factor-BB (10 ng/ml)-stimulated rat aortic smooth muscle cell proliferation (P < 0.01). This is the first study to demonstrate that NO plays a dual role in vascular cell proliferation, stimulating endothelial cells but inhibiting smooth muscle cell proliferation. This dual effect of NO on cell proliferation is associated with an in vivo reduction in neointimal thickening and an acceleration of endothelial recovery determined by both anatomic and functional methods.

Pathogenesis of atherosclerosis.

Cardiovascular disease is the leading cause of death in the United States. According to numbers compiled by the American Heart Association, nearly one of every two Americans dies of cardiovascular disease. For example, in 1987, 976,706 (46%) of the estimated 2,127,000 deaths recorded in the United States were attributable to diseases of the heart and blood vessels [1]. Most of these deaths can be attributed to atherosclerosis and its ensuing complications. The pathogenesis of atherosclerosis is not completely understood. Nevertheless, the purpose of this review is to provide an overview of how an atherosclerotic lesion might develop on the basis of our current understanding. This overview will focus on one hypothesis of atherosclerosis development, the modified response-to-injury hypothesis. Several additional hypotheses will be described briefly. These descriptions can serve as a framework on which researchers can build a more complete understanding of the processes involved in this complicated, multifactorial disease.

Drug delivery into the arterial wall: a time-course study with use of a lipophilic dye.

PURPOSE: One potential approach to the prevention of restenosis after angioplasty is to deliver antiproliferative agents directly to the angioplasty site. The purpose of this study was to determine the time course of drug penetration into the media of the balloon-dilated artery. MATERIALS AND METHODS: Balloon angioplasty of the left and right iliac arteries was performed once for 1 minute in each of five rabbits. A double-balloon catheter was then positioned at the site of angioplasty, and the fluorescent dye PKH26 (molecular weight, 961) was delivered under pressure to simulate drug delivery. Afterward, the arteries were removed and dye penetration into the media was measured on frozen cross sections by epifluorescence microscopy. RESULTS: Delivery of the dye was performed for periods ranging from 5 to 50 minutes at a mean pressure of 189 mm Hg. The depth of dye penetration (D, micrometers) was directly related to dye perfusion time (T, minutes) (D = 0.348T + 11.958, r = 0.496, P < .01). This equation predicts complete medial dye penetration in 81 minutes assuming an average intima-media thickness (40 microns). CONCLUSION: This study demonstrates that PKH26 can be delivered to the media of the dilated artery. However, the time required to obtain complete penetration may limit the utility of this double-balloon catheter approach to drug delivery.

Local delivery of an antiproliferative drug with use of hydrogel-coated angioplasty balloons.

PURPOSE: To determine the feasibility of using hydrogel-coated angioplasty balloons to deliver drugs that inhibit vascular smooth muscle cell (VSMC) proliferation. MATERIALS AND METHODS: In initial experiments, the tyrphostin RG-50872 (1 mumol/L) completely inhibited VSMC proliferation induced by platelet-derived growth factor (PDGF) in vitro when RG-50872 treatment preceeded PDGF exposure by 15 minutes. This inhibition was reversible and was not due to cell toxicity. In further experiments, hydrogel-coated and silicone-coated angioplasty balloons (2.5 mm in diameter by 20 mm in length) were coated with either 10 microL of RG-50872 (40 mmol/L in dimethyl sulfoxide [DMSO]) or DMSO vehicle, or were left uncoated. Afterward, each angioplasty balloon was inflated, submerged in 50 mL of culture media, and agitated for 2 minutes to promote drug release. Dilutions of this media were tested for their ability to inhibit VSMC proliferation. RESULTS: All hydrogel-coated balloons (n = 5) released sufficient RG-50872 to inhibit PDGF-induced VSMC proliferation by 95% or more, whereas none of the silicone-coated balloons (n = 4) did. DMSO-treated and untreated balloons had no effect on proliferation. CONCLUSION: These findings demonstrate that the hydrogel-coating on angioplasty balloons can take up and release sufficient RG-50872 to significantly inhibit smooth muscle cell proliferation. Further in vivo experiments are needed to determine if hydrogel-coated balloons can deliver sufficient RG-50872 to the arterial wall to affect VSMC proliferation.

Microwave thermal balloon angioplasty in the atherosclerotic rabbit.

We evaluated the angiographic and histologic response of the coronary vessels of the atherosclerotic rabbit to microwave thermal balloon angioplasty. Sixteen rabbits with atherosclerosis of the external iliac arteries following a high fat diet and endothelial denudation were treated with either CBA or MBA. Four weeks following angioplasty angiography was repeated, and following the death of the animals, the vessels treated were excised for histologic evaluation. In vessels with MBA with peak temperatures of 85 degrees C there was an increase in luminal diameter immediately postangioplasty, from 1.66 +/- 0.32 mm to 2.54 +/- 0.23 mm (p < 0.05). The diameter at 4 weeks (2.29 +/- 0.74 mm) remained increased compared with the preangioplasty diameter (p < 0.05). With microwave angioplasty at 70 degrees C there was an increase in luminal diameter, from 1.92 +/- 0.37 mm to 2.40 +/- 0.22 mm (p < 0.05) immediately postangioplasty. This increase in diameter was not sustained at 4 weeks (1.86 +/- 0.28 mm). In the vessels treated with CBA there was no significant increase in diameter noted either immediately postangioplasty or at 4 weeks postangioplasty. In the thermally treated vessels, histologic evaluation revealed a loss of lipid-laden cells; it also revealed the formation of a concentric hypocellular fibrotic layer. Microwave thermal balloon angioplasty at 85 degrees C results in enhancement of the immediate and delayed response to angioplasty. Modification of the proliferative response to angioplasty may be accomplished with this modality.

Use of Ferrum in MRI of lung parenchyma and pulmonary embolism.

MRI of lung parenchyma and pulmonary embolism (PE) remains challenging. "Ferrum," a ferric hydroxide sucrose complex used clinically for iron deficiency anemia for more than 40 years, was investigated as a negative MRI contrast agent in five rabbits bearing experimental PE as well as in five normal volunteers. Clots were prepared by spontaneous coagulation of 0.1 ml In-111 labeled autologous red blood cells and introduced through the jugular vein. Scintigraphic imaging permitted anatomical localization of PE in vivo and thereby served as a control for MR imaging. MRI was performed on a 1.5 T GE Signa scanner before and after induction of PE, and before and after the injection of Ferrum. T1-weighted images were obtained continuously for up to 90 min using varying doses of Ferrum. In five normal human volunteers, a single dose of 100 mg each was administered. T1- and T2-weighted spin-echo and gradient-echo images of lung parenchyma were repeatedly obtained before and after agent administration. In rabbit, Ferrum remained in circulation for several hours where it shortened both T1 and T2 of blood, improving the contrast between PE and lung parenchyma (i.e., intravascular compartment). A dose of 3 mg/kg was enough to increase the contrast-to-noise ratio (CNR) between PE and lung parenchyma by almost three fold, substantially improving lesion detectability. CNR increased up to five-fold when the dose was increased up to 20 mg/kg at which point CNR reached a plateau. In humans, T2-weighted spin-echo sequence appeared to be most sensitive to changes in signal-to-noise ratio (SNR) of normal lung parenchyma. Within 60 min after injection of 100 mg of iron, SNR dropped by 34% (p < .025). However, 24 hr later, SNR returned to almost normal. Ferrum increased the contrast between PE and lung parenchyma in the rabbit and decreased the parenchymal SNR in humans in nontoxic doses. These results suggest that Ferrum is worthy of further investigation of PE imaging in humans.

MR imaging of hepatic iron overload in rat.

To investigate the relationship of hepatic signal intensity and T2 with histologic grading in an animal model of oral iron overload and to determine the duration of feeding necessary to produce abnormalities detectable on magnetic resonance (MR) images, hepatic iron overload was induced in 12 rats by feeding them a diet supplemented with 4% carbonyl iron for 2-11 weeks. Iron overload seen on MR images was graded independently and blindly by two radiologists as normal, mild, moderate, or severe. The rats were killed, and histologic findings were graded blindly by four pathologists using a similar subjective scale. Hepatic T2 values were estimated from spin-echo images. In the rats with iron overload, intracellular iron deposition was noted on histologic studies. On MR images, hepatic signal intensity and T2 decreased after only 2 weeks of dietary iron overload, and both continued to decrease with longer duration of feeding. There was significant correlation between iron overload duration and changes on MR images and between MR images and histologic grading (r = .92, P = .0001 for both). The mean T2 of hepatic iron overload decreased with longer duration of feeding.

Amplification of serotonin-induced arterial contractions with thrombin.

The purpose of this study was to determine if exposure of arteries to thrombin increases arterial sensitivity to serotonin and could thereby promote vasospasm. Rings of rabbit abdominal aorta, with endothelium intact or removed, were pretreated with vehicle or thrombin (2.5 U/mL). Thereafter, arterial contractions in response to cumulative additions of serotonin were recorded. Arterial contractions were expressed as a percentage of maximal potassium chloride-induced contractions. Arterial sensitivity was expressed as the EC50, the concentration of serotonin that produced a half-maximal contraction. Exposure of aortic rings to thrombin alone produced contractions of 11% and 22% for rings with and without endothelium, respectively. Removal of the endothelium had no effect on maximal serotonin-induced contractions (93% with endothelium vs 98% without). In contrast, maximal serotonin-induced contractile force was increased after pretreatment with thrombin (107% vs 121% for rings with and without endothelium, respectively; P less than .01). Arterial sensitivity to serotonin was not affected by the removal of endothelium. However, thrombin pretreatment increased (P less than .01) arterial sensitivity to serotonin 2.6-fold and 4.7-fold for rings with and without endothelium, respectively. The results of this study demonstrate that arterial contractions due to serotonin are amplified by thrombin and suggest that vasospasm may be more likely to occur at sites in arteries where the endothelium is absent and both thrombin and serotonin are present.

Fatty liver. Chemical shift phase-difference and suppression magnetic resonance imaging techniques in animals, phantoms, and humans.

In vitro animal and human models were used to evaluate the potential of chemical shift magnetic resonance imaging (MRI) for assessing fatty liver. Phantoms of varying fat content were created from mayonnaise-agar preparations. Fatty liver was induced in eight rats by feeding them ethanol for three to six weeks (36% of total calories), whereas eight control rats were fed a normal diet. T1-weighted in-phase and opposed-phase MR images were obtained of the phantoms animals, and 28 human subjects. Additional images obtained in animals included long TR images with in-phase and opposed-phase technique, and hybrid chemical shift water and fat suppression. The rats were killed and histologic status was graded blindly by a hepatopathologist as normal, mild, moderate, or severe fatty change, for correlation with MR grading. Quantitative analysis of MR images included fat signal fraction for animals, and relative signal decrease between in-phase and opposed-phase images for phantom and human data. Phantom in-phase signal increased linearly with respect to fat content, whereas opposed-phase signal decreased linearly. MRI and histologic grading of rat livers were highly correlated, especially when based on water suppression images (r = 0.91, P = .0001). Opposed-phase images were also highly correlated, while fat suppression images were less effective. There was no overlap between MR-derived fat fractions for control (2.6%-5.7%) versus ethanol-fed rats (7.7%-17.9%, P = .0002). Human liver considered to be fatty by visual inspection (n = 8) had higher relative signal decrease than nonfatty liver (n = 22) (P less than .001). Phantom, animal, and human data demonstrate that comparison of T1-weighted in-phase and opposed-phase images is both practical and sensitive in the detection and grading of fatty liver.

Vascular smooth muscle contraction and relaxation: pathways and chemical modulation.

The purpose of this review has been to summarize the information learned in the past few years regarding the mechanisms responsible for smooth muscle contraction and relaxation and to relate this information to the vasoconstrictor and vasodilator agents used by the interventional radiologist. Because this review can only provide an overview of what is known about these processes, the reader is directed to the references cited below. This reference list contains review articles that will provide in-depth information about the topics presented herein.

Magnetic resonance chemical shift imaging and spectroscopy of atherosclerotic plaque.

An in vivo magnetic resonance imaging (MRI) technique for identification and characterization of atherosclerotic plaque was assessed in animal and human models. Atherosclerosis was induced in the abdominal aorta of four rabbits by a combination of balloon denudation and a high cholesterol diet. In vivo conventional spin-echo and fat/water suppressed images of the rabbit aortae were obtained at 1.5 T. Chemical shift imaging (CSI) was achieved using a hybridization of selective excitation and modified Dixon techniques. These techniques were then used to obtain images of atherosclerotic lesions in the carotid arteries of four patients prior to endarterectomy. The MRI results were corroborated by histologic and high-resolution proton MR spectroscopic (8.5 T) analysis of rabbit aorta, human carotid endarterectomy, and six additional human superficial femoral and iliac atherectomy specimens. All animal and human lesions were classified as either fatty streaks or fibrotic plaque. When compared to conventional spin-echo images, fat suppression by CSI substantially improved the measured contrast-to-noise ratio between plaque and vessel lumen, and enhanced its discrimination from periadventitial fat. In contrast, water suppression eliminated visualization of plaque due to the negligible amount of isotropic (liquid-like) signal from the immobilized lesion lipids. Magnetic resonance spectroscopy corroborated the CSI results by demonstrating broad, ill-defined fat resonances characteristic of nonmobile lipids in both human and rabbit atherosclerotic lesions. These findings indicate that in vivo MRI of plaque is technically feasible and can be markedly improved using chemical shift imaging.