Biomedical subjects

R M Judd

Publications and source records attributed to R M Judd.

At least 37 records · Page 2Linked to original sources

PubMed1997

Fast 23Na magnetic resonance imaging of acute reperfused myocardial infarction. Potential to assess myocardial viability.

BACKGROUND: The ability of the myocyte to maintain an ionic concentration gradient is perhaps the best indication of myocardial viability. We studied the relationship of 23Na MRI intensity to viability and explored the potential of fast-imaging techniques to reduce 23Na imaging times in rabbits and dogs. METHODS AND RESULTS: Eighteen rabbits underwent in situ coronary artery occlusion and reperfusion. The hearts were then either imaged following isolation and perfusion with cardioplegic solution (n = 6), imaged in vivo (n = 6), or analyzed for 23Na content and relaxation times (n = 12). Normal rabbits (n = 6) and dogs (n = 4) were imaged to examine the effect of animal size on 23Na image quality. 23Na imaging times were 7, 11, and 4 minutes for isolated rabbits, in vivo rabbits, and in vivo dogs, respectively. Infarcted, reperfused regions, identified by triphenyltetrazolium chloride staining, showed a significant elevation in 23Na image intensity compared with viable regions (isolated, 42 +/- 5%, P < .02; in vivo, 95 +/- 6%, P < .001), consistent with increased tissue sodium content. Similarly, 23Na MR spectroscopy showed that [Na+] was higher in nonviable than viable myocardium (isolated, 99 +/- 4 versus 61 +/- 2 mmol/L; in vivo, 91 +/- 2 versus 38 +/- 1 mmol/L; P < .001 for both). Image signal-to-noise ratios were higher in dogs than rabbits despite shorter imaging times, primarily due to larger voxels. CONCLUSIONS: Following acute infarction with reperfusion, a regional increase in 23Na MR image intensity is associated with nonviable myocardium. Fast gradient-echo imaging techniques reduce 23Na imaging times to a few minutes, suggesting that 23Na MR imaging has the potential to become a useful experimental and clinical tool.

Animals↗

PubMed1997

Techniques for high-speed cardiac magnetic resonance imaging in rats and rabbits.

Progress in research on hypertension, heart failure, aging, post-infarct remodeling, and the molecular basis of cardiovascular diseases in general has been greatly facilitated in recent years by the development of specialized small-mammal models by selective breeding and/or genetic alteration. Routine noninvasive evaluation of cardiac function and perfusion in these animals models, however, is difficult using existing methods. In principle, MRI can be used for this purpose, but in practice this is difficult because of problems related to RF coils, cardiac gating, and imaging pulse sequences. In this article, solutions to these problems are described that have allowed us to use MRI to routinely image the hearts of rats and rabbits. Specifically described are four RF coils, cardiac gating schemes, and an imaging pulse sequence specially designed for cardiac imaging in these animals on a 4.7 T Omega chemical-shift imaging (CSI) spectrometer. These techniques can be used to obtain, within 2 min, eight double-oblique short-axis images of the rat at different cardiac phases with 200 x 400 microm in-plane resolution and a slice thickness of 2 mm. Moreover, myocardial tissue tagging can be performed with tag thicknesses and separations comparable to those used routinely in humans. The technical information is presented in sufficient detail to allow researchers at other sites to reproduce the results. This information should facilitate the use of MRI for the noninvasive examination of cardiac function and perfusion, which can be combined with other established techniques for the study of cardiovascular disease in specialized animal models.

Animals↗

PubMed1997

Theoretical basis for sodium and potassium MRI of the human heart at 1.5 T.

Knowledge of the extent and location of viable tissue is important to clinical diagnosis. In principle, sodium (23Na) and potassium (39K) MRI could noninvasively provide information about tissue viability. In practice, imaging of these nuclei is difficult because, compared with water protons (1H), 23Na and 39K have lower MR sensitivities (9.2 and 0.051%, respectively), and lower in vivo concentrations (ca. 1000-fold). On the other hand, the relatively short T1 relaxation times of 23Na and 39K (ca. 30 and 10 ms, respectively) suggest that optimized imaging pulse sequences may in part alleviate the weak signal of these nuclei. In this study, numerical simulations of high-speed imaging sequences were developed and used to maximize 23Na and 39K image signal-to-noise ratio (SNR) per unit time within the constraints of existing gradient hardware. The simulation demonstrated that decreasing receiver bandwidth at the expense of echo time (TE) results in a substantial increase in 23Na and 39K image SNR/time despite the short T2 and T2* of these nuclei. Referenced to the available 1H signal on existing 1.5 T scanners, the simulation suggested that it should be possible to acquire three-dimensional 23Na images of the human heart with 7 x 7 x 7 mm resolution and 39K images with 26 x 26 x 26 mm resolution in 30 min. Experimentally in humans at 1.5 T, three-dimensional 23Na images of the heart were acquired in 15 min with 6 x 6 x 12 mm resolution and signal-to-noise ratios of 11 and 7 in the left ventricular cavity and myocardium, respectively, which is very similar to the predicted result. The results demonstrate that by choosing imaging pulse sequence parameters that fully exploit the short relaxation times of 23Na and 39K, potassium MRI is improved but remains impractical, whereas sodium MRI improves to the point where 23Na imaging of the human heart may be clinically feasible on existing 1.5 T scanners.

Heart Ventricles↗

PubMed1996

Myocardial Gd-DTPA kinetics determine MRI contrast enhancement and reflect the extent and severity of myocardial injury after acute reperfused infarction.

BACKGROUND: Contrast medium-enhanced magnetic resonance images of acute, reperfused infarcts have shown hypoenhanced and hyperenhanced regions in areas of injured myocardium. The precise mechanisms that lead to these altered enhancement patterns are unknown. This study was designed to evaluate possible mechanisms and to relate altered enhancement patterns to myocardial perfusion and viability. METHODS AND RESULTS: Thirteen rabbits underwent in situ coronary artery occlusion and reperfusion followed by isolated perfusion with cardioplegic solution. T1-weighted spin-echo images were acquired continuously during step changes in perfusate Gd-DTPA concentration. Regional blood flow was also measured by use of radioactive microspheres in all rabbits. There were marked differences in Gd-DTPA wash-in and washout time constants (wash-in, 0.8 +/- 0.1, 2.1 +/- 02, and 16.3 +/- 2.4 minutes, P < .001; washout, 1.6 +/- 0.1, 4.8 +/- 0.5, and 31.1 +/- 3.3 minutes, P < .001) in normal, infarct rim, and infarct core regions, respectively, resulting in differential enhancement of these regions. Microsphere flows in the infarct rim and core were 42.9 +/- 4.0% and 12.0 +/- 1.6% of normal myocardium and correlated well with washout time constants (r = .86, y = 0.77x - 0.002, P < .001), suggesting that these time constants index the severity of microvascular damage. In addition, spatial maps of washout time constants were produced. The extent of regions with abnormal time constants correlated well with triphenyltetrazolium chloride-determined infarct size (r = .94, y = 0.95x + 4.17, P < .001). CONCLUSIONS: In contrast-enhanced magnetic resonance images of acute, reperfused rabbit infarcts, differential image intensity is primarily due to regional differences in contrast agent wash-in and washout time constants. These regional differences in time constants also indicate the extent and severity of myocardial injury.

Analysis of Variance↗

PubMed1996

Intrinsic myocyte dysfunction and tyrosine kinase pathway activation underlie the impaired wall thickening of adjacent regions during postinfarct left ventricular remodeling.

BACKGROUND: Left ventricular remodeling after infarction is accompanied by dysfunction of regions adjacent to the infarct. We hypothesized that myocyte contractile abnormalities and elongation greater than in remote regions underlie adjacent-region dysfunction in the remodeled ventricle. The activation of the tyrosine kinase pathway, which mediates in vitro hypertrophy by stretch and/or angiotensin, was also assessed in myocytes separately isolated from adjacent and remote regions. METHODS AND RESULTS: ECG-gated magnetic resonance imaging short-axis images were acquired 2 weeks after coronary ligation in rats. After the rats were killed, myocytes were isolated from animals with large (n = 7) and small (n = 7) infarcts and from 4 sham-operated controls. Regional wall thickening was correlated with local myocyte function and morphology. Cytochemistry for tyrosine-phosphorylated proteins was performed in myocytes from the same regions. Remodeled ventricles were dilated relative to controls by 93.7%, and wall thickening in adjacent regions was less than in remote regions (27.8 +/- 6.11% versus 54.0 +/- 10.1%, P < .01). In large infarcts, cell extent and velocity of shortening were reduced in adjacent cells versus controls by 47% and 44%, respectively (P < .05). Myocyte shortening was reduced in adjacent versus remote regions (P < .06), and cell dysfunction correlated with impaired wall thickening (r = .72, P < .05). Myocytes in adjacent regions were longer than in remote regions (150.3 +/- 1.89 versus 143.1 +/- 1.76 microns, P < .05) and also showed 88% more membrane-related phosphotyrosine clusters (P < .05). CONCLUSIONS: After infarction, impaired wall thickening in adjacent regions is accompanied by greater myocyte dysfunction and elongation than in remote regions. These abnormalities are associated with regional differences in the tyrosine kinase pathway activation, indicating a potential intracellular mechanism for postinfarct myocardial remodeling.

Animals↗

PubMed1996

Compressibility of perfused passive myocardium.

In most theoretical analyses of the heart, the tissue has been assumed to be incompressible. Because the myocardium is extensively perfused with distensible vessels, increasing the stiffness of the surrounding tissue, as with contraction or passive stretching, should decrease the volume of fluid in these vessels. Using a digital subtraction angiographic method, we quantified the amount of vascular volume extruded from six passive, perfused canine interventricular septa during cyclic biaxial loading from 300 to 900 g force. At pressures from 0 to 120 mmHg the amount of fluid extruded during a loading cycle varied from 2 to 4 ml/100 g tissue at 0 and 120 mmHg, respectively. This volume change increased with perfusion pressure and was significantly greater at 120 than at 0, 30, or 60 mmHg. The amount of fluid extruded was on the same order as that estimated during active contraction or with a 60-mmHg change in perfusion pressure. The finding that perfused myocardium is compressible implies that results from existing analyses of the heart assuming incompressibility are not realistic. Such analyses must account for compressibility with, e.g., mixture theory or other similar approaches.

Angiography, Digital Subtraction↗

PubMed1995

Physiological basis of myocardial contrast enhancement in fast magnetic resonance images of 2-day-old reperfused canine infarcts.

BACKGROUND: Contrast-enhanced fast magnetic resonance (MR) images of acute, reperfused human infarcts demonstrate regions of hypoenhancement and hyperenhancement. The relations between the spatial extent and time course of these enhancement patterns to myocardial risk, infarct, and no-reflow regions have not been well characterized. METHODS AND RESULTS: The proximal left anterior descending coronary artery was occluded in 11 closed-chest dogs for 90 minutes followed by 2 days of reperfusion. Regional blood flow was determined by use of radioactive microspheres. The animals were studied at the 2-day time point with contrast-enhanced fast MRI (Signa 1.5 T, General Electric). Thioflavin-S was administered to demarcate no-reflow regions. The hearts were then excised, sectioned into five base-to-apex slices, stained with 2,3,5-triphenyltetrazolium chloride (TTC), and photographed under room light (for TTC) and ultraviolet light (for thioflavin). The spatial extents of thioflavin-negative, TTC-negative, and risk regions were compared planimetrically with MRI hypoenhanced and hyperenhanced regions. The spatial locations of subendocardial hypoenhancement in MR images correlated closely with those of thioflavin-negative regions. Microsphere blood flow in these regions was significantly reduced compared with remote regions (0.37 +/- 0.09 versus 0.88 +/- 0.10 mL/min per gram, respectively, P < .001) and with baseline (0.37 +/- 0.09 versus 0.87 +/- 0.15 mL/min per gram, P < .01). The spatial extent of hyperenhancement was smaller than the risk region (r = .64, slope = 0.48, P < .001) but highly correlated with TTC-negative regions and were, on average, 12% larger (r = .93, slope = 1.12, P = .035). CONCLUSIONS: In contrast-enhanced MR images of 2-day-old reperfused canine infarcts, myocardial regions of hypoenhancement are related to the no-reflow phenomenon. Approximately 90% of the myocardium within hyperenhanced regions is nonviable.

Animals↗

PubMed1995

Regional heterogeneity of human myocardial infarcts demonstrated by contrast-enhanced MRI. Potential mechanisms.

BACKGROUND: Myocardial reperfusion is pivotal to the prognosis of patients with acute myocardial infarction. In these patients, coronary flow is generally assessed by angiography and tissue perfusion by tracer scintigraphy. This study was designed to examine whether magnetic resonance imaging (MRI) provides information on myocardial perfusion and damage beyond that supplied by angiography and thallium scintigraphy after acute myocardial infarction. METHODS AND RESULTS: Twenty-two patients with recent myocardial infarction had ECG, echocardiography, coronary angiography, and fast contrast-enhanced MRI. Twelve patients also had exercise thallium scintigraphy. Time-intensity curves obtained from infarcted and noninfarcted regions were correlated with coronary anatomy and left ventricular function. Two perfusion patterns were observed in infarcted regions by comparison with the normal myocardial pattern. All patients but 1 had persistent myocardial hyperenhancement within the infarcted region up to 10 minutes after contrast. In 10 patients, this hyperenhanced region surrounded a subendocardial area of decreased signal at the center of the infarcted region associated with coronary occlusion at angiography, Q waves on ECG, and greater regional dysfunction by echocardiography. Moreover, the extent and location of the MRI abnormalities correlated well with the extent and location of the fixed single-photon emission computed tomography thallium defects. CONCLUSIONS: Large human infarcts, associated with prolonged obstruction of the infarct-related artery, are characterized by central dark zones surrounded by hyperenhanced regions on MRI. Conversely, reperfused infarcts with less regional dysfunction have uniform signal hyperenhancement. The MRI hyperenhanced segment correlates well with the fixed scintigraphic defect in patients with acute myocardial infarction.

Angioplasty, Balloon, Coronary↗

PubMed1995

Effects of myocardial water exchange on T1 enhancement during bolus administration of MR contrast agents.

Interpretation of first-pass myocardial perfusion studies employing bolus administration of T1 magnetic resonance (MR) contrast agents requires an understanding of the relationship between contrast concentration and image pixel intensity. The potential effects of myocardial water exchange rates among the intravascular, interstitial, and cellular compartments on this relationship are controversial. We directly studied these issues in isolated, nonbeating canine interventricular septa. Myocardial T1 was measured three times/s during bolus transit of intravascular (albumin-Gd-DTPA and polylysine-Gd-DTPA) and extracellular (gadoteridol) contrast agents. For polylysine-Gd-DTPA, the peak changes in myocardial 1/T1 (delta R1) scaled nonlinearly with perfusate contrast concentration whereas a linear relationship would be expected for fast water exchange among the vascular, interstitial, and cellular compartments. For all agents, the peak delta R1 were much smaller than the values expected on the basis of fast myocardial water exchange. The data demonstrate that in isolated myocardial tissue, myocardial T1 enhancement during bolus administration of contrast can be strongly affected by myocardial water exchange for both intravascular and extracellular MR contrast agents.

Albumins↗

PubMed1995

A magnetization-driven gradient echo pulse sequence for the study of myocardial perfusion.

A T1-weighted imaging pulse sequence for contrast-based studies of myocardial perfusion is presented and evaluated in phantoms and in vivo. The sequence is similar to spoiled gradient-recalled echo sequences except that nonselective preparatory RF pulses drive magnetization to steady state prior to image acquisition. Steady state is thus obtained in both tissue and blood resulting in a stable, homogeneous, and dark pre-contrast baseline. Tip angles and timings are chosen so that pixel intensity approximates a linear relation to 1/T1. The dynamic range of signal response to contrast agent concentration is greater than that of an inversion-recovery fast low angle shot sequence. The sequence proposed should be useful for myocardial perfusion studies.

Blood↗

PubMed1995

Validation of 19F-magnetic resonance determination of myocardial blood volume.

The use of perfluorochemical (PFC) emulsions to study the myocardial circulation by means of 19F NMR requires that the biodistribution of the PFC be known. The authors tested the hypothesis that PFC particles remain within the myocardial vascular space by infusing rats with both a PFC emulsion and 125I-albumin. Measurement of myocardial vascular volume by 19F NMR and by standard radiotracer analysis of the same tissue yielded concordant values by the two methods, establishing the PFC emulsion as an intravascular agent in this tissue. Perfluorochemical emulsions should be useful for the noninvasive study of myocardial vascular physiology by magnetic resonance.

Animals↗

PubMed1993

Models for coronary pressure-flow relationships.

We have developed a mathematical model which describes pressure-inflow relationships in the coronary circulation. Model parameters have been identified during metabolic and pharmacologic vasodilation. These two stimuli appear to affect resistance and back pressure in different ways. A possible explanation involving myogenic and metabolic effects is suggested.

Animals↗

PubMed1993

Direct evidence that coronary perfusion affects diastolic myocardial mechanical properties in canine heart.

OBJECTIVE: The effect of coronary perfusion on left ventricular chamber distensibility is only indirect evidence that perfusion alters the mechanical properties of the myocardium. The aim of this study was to demonstrate explicitly the effects of coronary perfusion on these mechanical properties. METHODS: The effects of different levels of coronary perfusion were studied both on in-plane stress-strain relations and on transverse stiffness in an isolated, perfused canine interventricular septal preparation. Additionally, to determine the vascular compartment responsible for the mechanical effects of perfusion on tissue properties, we examined the in-plane stress-strain responses and transverse stiffness after embolisation of the vasculature with 15 microns microspheres. RESULTS: The data show a clear dependence of tissue stress-strain properties on perfusion. The in-plane stress-strain relations were shifted to the left and transverse stiffness increased linearly as septal artery perfusion pressure increased. The dependence of both the in-plane stress-strain relations and transverse stiffness on perfusion was significantly decreased following embolisation. CONCLUSIONS: Myocardial tissue stiffness is directly related to perfusion. The linear relationship between transverse stiffness and perfusion makes it easier to assess the effects of perfusion on tissue stiffness than with in-plane stress-strain relations. Perfusion of capillaries and/or venules is largely responsible for these alterations in myocardial stiffness.

Animals↗

PubMed1993

Rapid measurements of diastolic intramyocardial vascular volume.

Rapid measurements of coronary vascular volume are necessary for a complete understanding of phasic coronary flow. Because no standard method is capable of making these measurements, we developed a method that uses digital subtraction angiography to image an intravascular contrast agent. The method is capable of measuring vascular volume in 33 ms and can be repeated three times per second. The method was first validated in phantoms. We then used this method to measure coronary vascular volume in the isolated, perfluorochemical-perfused, interventricular canine septum. The speed of the measurements allowed us, for the first time, to directly measure transients in vascular volume following sudden changes in perfusion pressure. At the steady-state and maximal vasodilation, coronary vascular volume varied from 7.5 +/- 1.2 (SE) ml/100 g at a perfusion pressure of 20 mmHg to 12.1 +/- 1.9 ml/100 g at 90 mmHg, which is similar to other reports. After a sudden change of 40 mmHg in perfusion pressure, vascular volume changed with a time constant of 3.2 +/- 0.3 (SE) s. Increasing ventricular wall stretch had no effect on either the steady-state volumes (P = 0.25) or the time constant for volume changes (P = 0.17). The fact that the time constant is longer than the cardiac cycle, yet much shorter than the time necessary to measure vascular volume using other methods, highlights the need for rapid measurements of vascular volume.

Absorptiometry, Photon↗

PubMed1992

Feasibility of 19F imaging of perfluorochemical emulsions to measure myocardial vascular volume.

19F magnetic resonance images were obtained of the ventricular walls of isolated rabbit hearts perfused with a perfluorochemical (PFC) emulsion. Since the PFC is known to stay within the vascular space in normal myocardial tissue, the 19F signal should reflect myocardial vascular volume. 19F MRI of PFC emulsions represents a new investigational tool for the study of coronary vascular volume.

Animals↗

PubMed1991

Diastolic coronary resistance and capacitance are independent of the duration of diastole.

Systolic myocardial contraction may produce changes in coronary resistance and capacitance that persist throughout a normal diastole. In addition, coronary resistance and capacitance as determined in the arrested heart may not accurately describe normal diastolic behavior. To evaluate these possibilities, an identification method capable of characterizing the input impedance of the coronary circulation in as little as 150 ms was developed. Using this method, coronary dynamics were measured during early and late diastoles in the beating heart with tone intact as well as during adenosine-induced maximal vasodilation. Coronary dynamics were also measured in the arrested heart during maximal vasodilation. With vasomotor tone intact, the parameters of a lumped model of the coronary circulation showed no variation from early to late diastole. During maximal vasodilation, model parameters also showed no variation from early to late diastole. Parameters in the arrested heart were not statistically different from those of the beating heart during maximal vasodilation. However, model parameters determined during maximal vasodilation were significantly different from those determined with tone intact. These results suggest that although coronary resistance and capacitance are dependent on vasomotor tone, they remain constant throughout diastole and remain similar in the arrested heart.

Animals↗

PubMed1991

Coronary input impedance is constant during systole and diastole.

Although it is well known that coronary inflow decreases substantially during systole, the mechanism responsible for this decrease remains controversial. Knowledge of how coronary input impedance is affected by contraction can differentiate between some of the proposed mechanisms. In open-chest dogs, we have measured coronary inflow in the beating heart both during constant-pressure perfusion and during 10-Hz sinusoidal pressure oscillations around the same constant pressure. By exploiting the principle of superposition, we have shown that coronary input impedance remains unchanged between systole and diastole. Using this result, we have shown that a simple lumped-parameter model with constant resistance and compliance can describe coronary inflow at heart rates of 60, 90, 120, and 150 beats/min both with vasomotor tone intact and during maximal coronary vasodilation. Coronary resistance and compliance determined using the model are comparable to those obtained in our laboratory and by others during normal diastoles and in the arrested heart. The results suggest that, despite large increases in myocardial tissue stresses during systole, coronary resistance and compliance as determined using inflow measurements are constant during systole and diastole.

Animals↗

PubMed1991

First-pass entry of nonionic contrast agent into the myocardial extravascular space. Effects on radiographic estimates of transit time and blood volume.

BACKGROUND: Almost all x-ray-based techniques intended to assess regional myocardial perfusion from myocardial concentration-time curves following the administration of soluble contrast agents assume that these agents behave as intravascular indicators and can therefore provide measurements of intravascular transit time and intramyocardial blood volume. METHODS AND RESULTS: We tested this assumption by comparing a conventional nonionic contrast agent (ioversol) to a particulate emulsion (ethiodol) that remained in the vascular space in closed-chest dogs during pharmacological vasodilation. Using fast computed tomography (CT), pairs of myocardial CT intensity-time curves were obtained following sequential bolus aortic administration of the two contrast agents. The emulsion (particle size less than 3 microns) was almost completely washed out of the myocardial region of interest within a few seconds, as would be anticipated for a vascular indicator. At the onset of recirculation, CT intensity for ethiodol fell to 5 +/- 1% (SEM) of peak values in normally perfused areas and to 10 +/- 4% of peak values in an area in which flow had been reduced by 50% by a chronically implanted coronary artery occluder (p = NS). In comparison, the diffusible nonionic contrast agent ioversol showed substantial intramyocardial retention at the onset of recirculation. At the time of recirculation, CT intensities for ioversol averaged 36 +/- 2% of peak values in normally perfused nonstenotic areas and 54 +/- 4% of peak values in stenotic areas (p less than 0.01). Using residue function analysis for a diffusible indicator, first-pass extractions of the conventional nonionic agent averaged 33 +/- 2% in normally perfused areas and 50 +/- 3% in stenotic areas (p less than 0.01). Because of the significant first-pass myocardial retention of ioversol, both mean myocardial appearance time and intramyocardial blood volume were consistently overestimated. CONCLUSIONS: Soluble radiographic contrast agents, like other small molecules, enter the interstitial space to a degree, which is important because it affects estimates of myocardial perfusion based on transit time and intramyocardial blood volume. Indicator dilution models intended to quantify myocardial perfusion with conventional radiographic contrast agents need to account for this extravascular exchange.

Animals↗