Achievable aspiration flow rates with large balloon guide catheters during carotid artery stenting.

BACKGROUND: Emergency carotid artery stenting (CAS) is a frequent endovascular procedure, especially in combination with intracranial thrombectomy. Balloon guide catheters are frequently used in these procedures. Our aim was to determine if mechanical aspiration through the working lumen of a balloon occlusion catheter during the steps of a carotid stenting procedure achieve flow rates that may lead to internal carotid artery (ICA) flow reversal which consecutively may prevent distal embolism. METHODS: Aspiration experiments were conducted using a commercially available aspiration pump. Aspiration flow rates/min with 6 different types of carotid stents inserted into a balloon guide catheter were measured. Measurements were repeated three times with increasing pressure in the phantom. To determine if the achieved aspiration flow rates were similar to physiologic values, flow rates in the ICA and external carotid artery (ECA) in 10 healthy volunteers were measured using 4D-flow MRI. RESULTS: Aspiration flow rates ranged from 25 to 82 mL/min depending on the stent model. The pressure in the phantom had a significant influence on the aspiration volume. Mean blood flow volumes in volunteers were 210 mL/min in the ICA and 101 mL/min in the ECA. CONCLUSIONS: Based on the results of this study, flow reversal in the ICA during common carotid artery occlusion is most likely achieved with the smallest diameter stent sheath and the stent model with the shortest outer stent sheath maximum diameter. This implies that embolic protection during emergency CAS through aspiration is most effective with these models.

Pulmonary Embolism Detection with Three-dimensional Ultrashort Echo Time MR Imaging: Experimental Study in Canines.

PURPOSE: To demonstrate the feasibility of free-breathing three-dimensional (3D) radial ultrashort echo time (UTE) magnetic resonance (MR) imaging in the simultaneous detection of pulmonary embolism (PE) and high-quality evaluation of lung parenchyma. MATERIALS AND METHODS: The institutional animal care committee approved this study. A total of 12 beagles underwent MR imaging and computed tomography (CT) before and after induction of PE with autologous clots. Breath-hold 3D MR angiography and free-breathing 3D radial UTE (1.0-mm isotropic spatial resolution; echo time, 0.08 msec) were performed at 3 T. Two blinded radiologists independently marked and graded all PEs on a four-point scale (1 = low confidence, 4 = absolutely certain) on MR angiographic and UTE images. Image quality of pulmonary arteries and lung parenchyma was scored on a four-point-scale (1 = poor, 4 = excellent). Locations and ratings of emboli were compared with reference standard CT images by using an alternative free-response receiver operating characteristic curve (AFROC) method. Areas under the curve and image quality ratings were compared by using the F test and the Wilcoxon signed-rank test. RESULTS: A total of 48 emboli were detected with CT. Both readers showed higher sensitivity for PE detection with UTE (83% and 79%) than with MR angiography (75% and 71%). The AFROC area under the curve was higher for UTE than for MR angiography (0.95 vs 0.89), with a significant difference in area under the curve of 0.06 (95% confidence interval: 0.01, 0.11; P = .018). UTE image quality exceeded that of MR angiography for subsegmental arteries (3.5 ± 0.7 vs 2.9 ± 0.5, P = .002) and lung parenchyma (3.8 ± 0.5 vs 2.2 ± 0.2, P < .001). The apparent signal-to-noise ratio in pulmonary arteries and lung parenchyma was significantly higher for UTE than for MR angiography (41.0 ± 5.2 vs 24.5 ± 6.2 [P < .001] and 10.2 ± 1.8 vs 3.5 ± 0.8 [P < .001], respectively). The apparent contrast-to-noise ratio between arteries and PEs was higher for UTE than for MR angiography (20.3 ± 5.2 vs 15.4 ± 6.7, P = .055). CONCLUSION: In a canine model, free-breathing 3D radial UTE performs better than breath-hold 3D MR angiography in the detection of PE and yields better image quality for visualization of small vessels and lung parenchyma. Free-breathing 3D radial UTE for detection of PE is feasible and warrants evaluation in human subjects.

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.

Measurements of wall shear stress and aortic pulse wave velocity in swine with familial hypercholesterolemia.

PURPOSE: To assess measurements of pulse wave velocity (PWV) and wall shear stress (WSS) in a swine model of atherosclerosis. MATERIALS AND METHODS: Nine familial hypercholesterolemic (FH) swine with angioplasty balloon catheter-induced atherosclerotic lesions to the abdominal aorta (injured group) and 10 uninjured FH swine were evaluated with a 4D phase contrast (PC) magnetic resonance imaging (MRI) acquisition, as well as with radial and Cartesian 2D PC acquisitions, on a 3T MR scanner. PWV values were computed from the 2D and 4D PC techniques, compared between the injured and uninjured swine, and validated against reference standard pressure probe-based PWV measurements. WSS values were also computed from the 4D PC MRI technique and compared between injured and uninjured groups. RESULTS: PWV values were significantly greater in the injured than in the uninjured groups with the 4D PC MRI technique (P = 0.03) and pressure probes (P = 0.02). No significant differences were found in PWV between groups using the 2D PC techniques (P = 0.75-0.83). No significant differences were found for WSS values between the injured and uninjured groups. CONCLUSION: The 4D PC MRI technique provides a promising means of evaluating PWV and WSS in a swine model of atherosclerosis, providing a potential platform for developing the technique for the early detection of atherosclerosis.

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.

Noninvasive assessment of transstenotic pressure gradients in porcine renal artery stenoses by using vastly undersampled phase-contrast MR angiography.

PURPOSE: To compare noninvasive transstenotic pressure gradient (TSPG) measurements derived from high-spatial- and temporal-resolution four-dimensional magnetic resonance (MR) flow measurements with invasive measurements obtained from endovascular pressure wires with digital subtraction angiographic guidance. MATERIALS AND METHODS: After Animal Care and Use Committee approval, bilateral renal artery stenosis (RAS) was created surgically in 12 swine. Respiratory-gated phase-contrast vastly undersampled isotropic projection (VIPR) MR angiography of the renal arteries was performed with a 1.5-T clinical MR system (repetition time, 11.4 msec; echo time [first echo], 3.7 msec; 18,000 projection angles; imaging volume, 260 × 260 × 200 mm; acquired isotropic spatial resolution, 1.0 × 1.0 × 1.0 mm; velocity encoding, 150 cm/sec). Velocities measured with phase-contrast VIPR were used to calculate TSPGs by using Navier-Stokes equations. These were compared with endovascular pressure measurements (mean and peak) performed by using fluoroscopic guidance with regression analysis. RESULTS: In 19 renal arteries with an average stenosis of 62% (range, 0%-87%), there was excellent correlation between the noninvasive TSPG measurement with phase-contrast VIPR and invasive TSPG measurement for mean TSPG (R² = 95.4%) and strong correlation between noninvasive TSPG and invasive TSPG for the peak TSPG measures (R² = 82.6%). The phase-contrast VIPR-derived TSPG measures were slightly lower than the endovascular measurements. In four arteries with severe stenoses and one occlusion (mean, 86%; range, 75%-100%), the residual lumen within the stenosis was too small to determine TSPG with phase-contrast VIPR. CONCLUSION: The unenhanced MR angiographic technique with phase-contrast VIPR allows for accurate noninvasive assessment of hemodynamic significance in a porcine model of RAS with highly accurate TSPG measurements.

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.

The effects of botulinum toxin A on muscle histology during distraction osteogenesis.

Distraction osteogenesis is a highly successful method of bone formation, yet muscle fibrosis and contractures can result in significant morbidity. In the current study, we investigate the efficacy of botulinum toxin A in preventing fibrosis and potentially increasing muscle development in distracted muscles. Fifteen New Zealand White rabbits underwent tibial distraction at 1.5 mm/day until a 20% gain was achieved. Treatment groups were divided by drug (saline or botulinum toxin) and target muscle (gastrocnemius or tibialis anterior). Two additional control animals received no treatment. Bromeodeoxyuridine was delivered continuously throughout the 8-week experiment, and following muscle harvest. Tissues were stained for BrdU, Pax-7, vimentin, and haematoxylin and eosin staining. Mitotic activity increased in all distracted animals; however, in the animals receiving botulinum toxin A injections into the gastrocnemius, the antagonist tibialis anterior suffered up to 9% less fibrosis than distraction alone (p = 0.024). Use of botulinum A toxin did not appear to promote or improve neogenesis of muscle fibers, nor did it decrease fibrosis in the injected muscles. It appears from this study, and a previously published study on the effects of this toxin on muscle function, that botulinum A toxin maybe of some benefit in decreasing morbidity in the antagonist muscle but not the muscle injected with the toxin.

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.