Accuracy of Doppler echocardiographic estimates of pulmonary artery pressures in a canine model of pulmonary hypertension.

OBJECTIVES: To compare noninvasive estimates of pulmonary artery pressure (PAP) obtained via echocardiography (ECHO) to invasive measurements of PAP obtained during right heart catheterization (RHC) across a range of PAP. To examine the accuracy of estimating right atrial pressure via ECHO (RAPECHO) compared to RAP measured by RHC (RAPRHC), and determine if adding RAPECHO improves the accuracy of noninvasive PAP estimations. ANIMALS: 14 healthy female beagle dogs. METHODS: Comparison of ECHO and RHC measures of PAP, both at normal PAP and increased PAP generated by microbead embolization. RESULTS: Noninvasive estimates of PAP were moderately but significantly correlated (r of 0.68-0.78; p < 0.0006) with invasive measurements of PAP. Wide variance was noted for all estimations, with increased variance at higher PAP. The addition of RAPECHO improved correlation and bias in all cases. RAPRHC was significantly correlated with RAPECHO (r = 0.38; p = 0.04) as estimated by the ellipse area method. Median RAPRHC was significantly different between 3 subjective assessments of right atrial size (p = 0.037). CONCLUSIONS: Spectral Doppler assessments of tricuspid and pulmonic regurgitation are imperfect methods for predicting PAP as measured by catheterization despite an overall moderate correlation between invasive and noninvasive values. Noninvasive measurements may be better utilized as part of a comprehensive assessment of PAP in canine patients. RAPRHC appears best estimated based on subjective assessment of RA size. Including estimated RAPECHO in estimates of PAP improves the correlation and relatedness between noninvasive and invasive measures of PAP, but notable variability in accuracy of estimations persists.

Preliminary in vivo evaluation of a novel intrasaccular cerebral aneurysm occlusion device.

OBJECTIVE: Current endovascular technology does not offer a perfect solution for all cerebral aneurysms. Our group has built two versions of a novel aneurysm intrasaccular occlusion device (AIOD) to address the drawbacks associated with current occlusion devices. The objective of the present study was to perform pilot proof of concept in vivo testing of this new AIOD in swine and canines. METHODS: Two configurations of the AIOD, termed 'coil-in-shell' and 'gel-in-shell', were implanted in surgically created sidewall aneurysms (n=4) in swine for acute occlusion studies, as well as sidewall (n=8) and bifurcation aneurysms (n=3) in canines to assess long term occlusion efficacy. Occlusion at all time points (immediate, 6 weeks, and 12 weeks) was evaluated by angiography. Neointimal healing at 12 weeks post-implantation in canines was examined histologically. RESULTS: Angiographic analysis showed that both the coil-in-shell and gel-in-shell devices achieved complete aneurysm occlusion immediately following device delivery in sidewall aneurysms in swine. In longer term canine studies, initial occlusion ranged from 71.3% to 100%, which was stable with no recurrence in any of the sidewall aneurysms at 6 or 12 weeks. Histological analysis at 12 weeks showed mature fibromuscular tissue at the neck of all aneurysms and no significant inflammatory response. CONCLUSIONS: The AIOD tested in this study showed promise in terms of acute and chronic occlusion of aneurysms. Our findings suggest that these devices have the potential to promote robust tissue healing at the aneurysm neck, which may minimize aneurysm recurrence. Although proof of principle has been shown, further work is needed to deliver this device through an endovascular route.

Pulmonary artery relative area change is inversely related to ex vivo measured arterial elastic modulus in the canine model of acute pulmonary embolization.

A low relative area change (RAC) of the proximal pulmonary artery (PA) over the cardiac cycle is a good predictor of mortality from right ventricular failure in patients with pulmonary hypertension (PH). The relationship between RAC and local mechanical properties of arteries, which are known to stiffen in acute and chronic PH, is not clear, however. In this study, we estimated elastic moduli of three PAs (MPA, LPA and RPA: main, left and right PAs) at the physiological state using mechanical testing data and correlated these estimated elastic moduli to RAC measured in vivo with both phase-contrast magnetic resonance imaging (PC-MRI) and M-mode echocardiography (on RPA only). We did so using data from a canine model of acute PH due to embolization to assess the sensitivity of RAC to changes in elastic modulus in the absence of chronic PH-induced arterial remodeling. We found that elastic modulus increased with embolization-induced PH, presumably a consequence of increased collagen engagement, which corresponds well to decreased RAC. Furthermore, RAC was inversely related to elastic modulus. Finally, we found MRI and echocardiography yielded comparable estimates of RAC. We conclude that RAC of proximal PAs can be obtained from either MRI or echocardiography and a change in RAC indicates a change in elastic modulus of proximal PAs detectable even in the absence of chronic PH-induced arterial remodeling. The correlation between RAC and elastic modulus of proximal PAs may be useful for prognoses and to monitor the effects of therapeutic interventions in patients with PH.

Impact of acute pulmonary embolization on arterial stiffening and right ventricular function in dogs.

Pulmonary hypertension (PH) can impact right ventricular (RV) function and alter pulmonary artery (PA) stiffness. The response of the RV to an acute increase in pulmonary pressure is unclear. In addition, the relation between total pulmonary arterial compliance and local PA stiffness has not been investigated. We used a combination of right heart catheterization (RHC) and magnetic resonance imaging (MRI) to assess PA stiffening and RV function in dogs before and after acute embolization. We hypothesized that in moderate, acute PH the RV is able to compensate for increased afterload, maintaining adequate coupling. Also, we hypothesized that in the absence of PA remodeling the relative area change in the proximal PA (RAC, a noninvasive index of local area strain) correlates with the total arterial compliance (stroke volume-to-pulse pressure ratio). Our results indicate that, after embolization, RV function is able to accommodate the demand for increased stroke work without uncoupling, albeit at the expense of a reduction of efficiency. In this acute model, RAC showed excellent correlation with total arterial compliance. We used this correlation to assess PA pulse pressure (PP) from noninvasive MRI measurements of stroke volume and RAC. We demonstrated that in acute pulmonary embolism MRI estimates of PP are remarkably close to measurements from RHC. These results, if confirmed in chronic PH and clinically, suggest that monitoring of PH progression by noninvasive methods may be possible.

CT perfusion in the treatment of a swine model of unilateral renal artery stenosis: validation with microspheres.

PURPOSE: To assess the feasibility of using current computed tomography (CT) perfusion techniques for evaluating unilateral renal artery stenosis (RAS) with assessment of pre- and posttreatment perfusion and to compare those results against the standard of microsphere injection. MATERIALS AND METHODS: Six juvenile swine with surgically created right RAS were examined in a combined angiography-CT suite. CT perfusion, injection of fluorescent microspheres, and digital subtraction angiography were performed before and after release of the stenosis. Cortical horseshoe-shaped regions of interest were used to measure blood flow (in milliliters/[100 g min]). Two cortical samples (superior and inferior) from each kidney were excised and sent to a reference laboratory for microsphere analysis. The relative blood flow ratio (RBFR) and posttherapy increase in blood flow were determined. The Pearson product correlation was calculated to compare the absolute blood flow, pretherapy RBFR, and posttherapy increase in blood flow between the two techniques. Bland-Altman analysis of the absolute blood flow measurements was performed. RESULTS: Forty-eight blood flow measurements showed moderate correlation (r = 0.712, P < .001). However, Bland-Altman plots (bias, -19.21; limits of agreement, -156.1 to 117.7 mL/[100 g . min]) showed poor agreement. Measurements of RBFR with CT correlated well with microsphere data. Pretherapy RBFR showed moderate correlation with microsphere data (r = 0.859, P < .001, n = 12), whereas the posttherapy increase in blood flow was highly correlated (r = 0.898, P < .001, n = 12). CONCLUSIONS: CT perfusion and microspheres produce similar indexes of relative renal cortical perfusion when normalized to the unaffected kidney. Further work is needed to determine the clinical utility of CT perfusion for pre- and posttherapy decision making.

Transstenotic pressure gradients: measurement in swine--retrospectively ECG-gated 3D phase-contrast MR angiography versus endovascular pressure-sensing guidewires.

PURPOSE: To prospectively evaluate the hypothesis that retrospectively electrocardiographically gated phase contrast with vastly undersampled isotropic projection reconstruction (VIPR) magnetic resonance (MR) angiography data sets can be used to measure transstenotic pressure gradients (TSPGs) in vivo. MATERIALS AND METHODS: TSPGs were calculated by using phase-contrast VIPR MR angiography data sets; measurements obtained with a pair of endovascular pressure-sensing guidewires served as a reference standard. With institutional animal care and use committee approval, 12 swine underwent surgical creation of stenoses at the left common carotid, right renal, and left external iliac arteries. The percentage stenosis and reference diameter of the lesions were calculated from conventional digital subtraction angiograms. A pair of 0.014-inch pressure-sensing guidewires was placed in tandem; sensors 1 cm distal and 1 cm proximal to the lesions measured the mean TSPG. Phase-contrast VIPR phase difference images were analyzed with an iterative technique based on the Navier-Stokes equations to determine the mean TSPG. Pearson product correlation was calculated, and Bland-Altman plots were generated to determine the degree of agreement between the two methods. RESULTS: Twenty-one lesions (12 carotid, nine iliac; mean percentage stenosis, 52.4%; range, 29.8%-64.9%; mean reference diameter, 3.4 mm; range, 2.4-5.6 mm) were analyzed. For carotid and iliac lesions, phase-contrast VIPR and guidewire TSPG measurements were highly correlated (r = 0.952, P < .001). Bland-Altman plots (bias, 0.86 mm Hg; limits of agreement: -6.17 to 7.88 mm Hg) showed good agreement. Measurements in renal lesions (n = 9) were poorly correlated (r = -0.081, P = .835) and were excluded because of image degradation secondary to respiratory motion. CONCLUSION: Phase-contrast MR angiography with VIPR enables reliable measurements of TSPG in carotid and iliac lesions that are comparable to those obtained with endovascular pressure-sensing guidewires. However, further work to compensate for respiratory motion is required to extend this technique to the renal arteries.

Detection of acute renal ischemia in swine using blood oxygen level-dependent magnetic resonance imaging.

PURPOSE: To determine the feasibility and sensitivity of blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) to detect acute renal ischemia, using a swine model, and to present the causes of variability and assess techniques that minimize variability introduced during data analysis. MATERIALS AND METHODS: BOLD MRI was performed in axial and coronal planes of the kidneys of five swine. Color R2* maps were calculated and mean R2* values and 95% confidence intervals (CIs) for the cortex and medulla were determined for baseline, renal artery occlusion and reperfusion conditions. Paired Student's t-tests were used to determine significance. RESULTS: Mean R2* measurements increased from baseline during renal artery occlusion in the cortex (axial, 13.8-24.6 second(-1); coronal, 14.4-24.7 second(-1)) and medulla (axial, 19.3-32.2 second(-1); coronal, 20.1-30.7 second(-1)). These differences were significant for both the cortex (axial, P < 0.04; coronal, P < 0.005) and medulla (axial, P < 0.02; coronal, P < 0.0005). No significant change was observed in the contralateral kidney. CONCLUSION: R2* values were significantly higher than baseline for medulla and cortex during renal artery occlusion. More variability exists in R2* measurements in the medulla than the cortex and in the axial than the coronal plane.