RESUMEN
Imaging arterial mechanical properties may improve vascular disease diagnosis. Pulse wave velocity (PWV) is a marker of arterial stiffness linked to cardio-vascular mortality. Pulse wave imaging (PWI) is a technique for imaging the pulse wave propagation at high spatial and temporal resolution. In this paper, we introduce adaptive PWI, a technique for the automated partition of heterogeneous arteries into individual segments characterized by most homogeneous pulse wave propagation, allowing for more robust PWV estimation. This technique was validated in a silicone phantom with a soft-stiff interface. The mean detection error of the interface was 4.67 ± 0.73 mm and 3.64 ± 0.14 mm in the stiff-to-soft and soft-to-stiff pulse wave transmission direction, respectively. This technique was tested in monitoring the progression of atherosclerosis in mouse aortas in vivo ( n = 11 ). The PWV was found to already increase at the early stage of 10 weeks of high-fat diet (3.17 ± 0.67 m/sec compared to baseline 2.55 ± 0.47 m/sec, ) and further increase after 20 weeks of high-fat diet (3.76±1.20 m/sec). The number of detected segments of the imaged aortas monotonically increased with the duration of high-fat diet indicating an increase in arterial wall property inhomogeneity. The performance of adaptive PWI was also tested in aneurysmal mouse aortas in vivo. Aneurysmal boundaries were detected with a mean error of 0.68±0.44 mm. Finally, initial feasibility was shown in the carotid arteries of healthy and atherosclerotic human subjects in vivo ( n = 3 each). Consequently, adaptive PWI was successful in detecting stiffness inhomogeneity at its early onset and monitoring atherosclerosis progression in vivo.
Asunto(s)
Interpretación de Imagen Asistida por Computador/métodos , Ultrasonografía/métodos , Anciano , Algoritmos , Animales , Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aterosclerosis/diagnóstico por imagen , Arterias Carótidas/diagnóstico por imagen , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Fantasmas de ImagenRESUMEN
Purpose To assess whether the stability of murine aortic aneurysms is associated with the homogeneity of pulse wave propagation within the saccular wall. Materials and Methods All animal procedures were approved by the institutional Animal Care and Use Committee. Apolipoprotein E and tissue inhibitor of metalloproteinases-1 knockout mice (n = 26) were infused with angiotensin II by using subcutaneously implanted osmotic pumps, with an additional control mouse used for histologic examination (n = 1). Pulse wave imaging (PWI) was performed just before infusion and 15 days after infusion by using 40-MHz ultrasonography at 8000 frames per second (with electrocardiographic gating). Aneurysm appearance on B-mode images was monitored every 2-3 days for 30 days. On the basis of B-mode images obtained after 30 days, aneurysms were deemed to have been unstable if they had ruptured; otherwise, they were deemed stable. Statistical significance was assessed by using two-tailed t tests. Results In normal aortas, the pulse waves propagated at relatively constant velocities (mean ± standard deviation, 2.8 m/sec ± 0.9). Fifteen days after infusion, all mice had developed aneurysms, with significant (P < .001/12) changes in maximum anterior-posterior diameter (increase of 54.9% ± 2.5) and pulse wave velocity (PWV) (decrease of 1.3 m/sec ± 0.8). While there was no significant difference in these parameters (P = .45 for diameter and P = .55 for PWV) between stable aneurysms (n = 12) and unstable aneurysms (n = 14), the standard deviation of the high-resolution PWV was significantly higher (P < .001/12) in unstable aneurysms (5.7 m/sec ± 1.6) than in stable ones (3.2 m/sec ± 0.9). Conclusion High-resolution PWI was used to measure the local homogeneity of pulse wave propagation within the saccular wall, which is lower in unstable aneurysms than in stable ones. Hence, if proven to add additional information beyond size and appearance in human studies, PWI could potentially be used to assess the stability of aneurysms by providing information that is complementary to the anatomic data obtained with conventional B-mode imaging. © RSNA, 2016 Online supplemental material is available for this article.
Asunto(s)
Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Rotura de la Aorta/diagnóstico por imagen , Animales , Aneurisma de la Aorta Abdominal/fisiopatología , Rotura de la Aorta/fisiopatología , Apolipoproteínas E/deficiencia , Masculino , Ratones Noqueados , Análisis de la Onda del Pulso , Inhibidor Tisular de Metaloproteinasa-1/deficiencia , UltrasonografíaRESUMEN
Atherosclerosis and Abdominal Aortic Aneurysms (AAAs) are two common vascular diseases associated with mechanical changes in the arterial wall. Pulse Wave Imaging (PWI), a technique developed by our group to assess and quantify the mechanical properties of the aortic wall in vivo, may provide valuable diagnostic information. This work implements piecewise PWI (pPWI), an enhanced version of PWI designed for focal vascular diseases. Localized, sub-regional PWVs and PWI moduli ( EPWI ) were estimated within 2-4 mm wall segments of murine normal, atherosclerotic and aneurysmal arteries. Overall, stiffness was found to increase in the atherosclerotic cases. The mean sub-regional PWV was found to be 2.57±0.18 m/s for the normal aortas (n = 7) with a corresponding mean EPWI of 43.82±5.86 kPa. A significant increase ( (p ≤ 0.001)) in the group means of the sub-regional PWVs was found between the normal aortas and the aortas of mice on high-fat diet for 20 ( 3.30±0.36 m/s) and 30 weeks ( 3.56±0.29 m/s). The mean of the sub-regional PWVs ( 1.57±0.78 m/s) and EPWI values ( 19.23±15.47 kPa) decreased significantly in the aneurysmal aortas (p ≤ 0.05) . Furthermore, the mean coefficient of determination (r(2)) of the normal aortas was significantly higher (p ≤ 0.05) than those of the aneurysmal and atherosclerotic cases. These findings demonstrated that pPWI may be able to provide useful biomarkers for monitoring focal vascular diseases.
Asunto(s)
Aorta/diagnóstico por imagen , Arterias Carótidas/diagnóstico por imagen , Análisis de la Onda del Pulso/métodos , Animales , Aorta/patología , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/patología , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/patología , Arterias Carótidas/patología , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/patología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Masculino , Ratones , Ratones Noqueados , UltrasonografíaRESUMEN
The abdominal aortic aneurysm (AAA) is a silent and often deadly vascular disease caused by the localized weakening of the arterial wall. Previous work has indicated that local changes in wall stiffness can be detected with pulse wave imaging (PWI), which is a non-invasive technique for tracking the propagation of pulse waves along the aorta at high spatial and temporal resolutions. The aim of this study was to assess the capability of PWI to monitor and stage AAA progression in a murine model of the disease. ApoE/TIMP-1 knockout mice (N = 18) were given angiotensin II for 30 days via subcutaneously implanted osmotic pumps. The suprarenal sections of the abdominal aortas were imaged every 2-3 d after implantation using a 30-MHz VisualSonics Vevo 770 with 15-µm lateral resolution. Pulse wave propagation was monitored at an effective frame rate of 8 kHz by using retrospective electrocardiogram gating and by performing 1-D cross-correlation on the radiofrequency signals to obtain the displacements induced by the waves. In normal aortas, the pulse waves propagated at constant velocities (2.8 ± 0.9 m/s, r(2) = 0.89 ± 0.11), indicating that the composition of these vessels was relatively homogeneous. In the mice that developed AAAs (N = 10), the wave speeds in the aneurysm sac were 45% lower (1.6 ± 0.6 m/s) and were more variable (r(2) = 0.66 ± 0.23). Moreover, the wave-induced wall displacements were at least 80% lower within the sacs compared with the surrounding vessel. Finally, in mice that developed fissures (N = 5) or ruptures (N = 3) at the sites of their AAA, higher displacements directed out of the lumen and with no discernible wave pattern (r(2) < 0.20) were observed throughout the cardiac cycle. These findings indicate that PWI can be used to distinguish normal murine aortas from aneurysmal, fissured and ruptured ones. Hence, PWI could potentially be used to monitor and stage human aneurysms by providing information complementary to standard B-mode ultrasound.
Asunto(s)
Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Animales , Aneurisma de la Aorta Abdominal/patología , Técnicas de Imagen Sincronizada Cardíacas , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Procesamiento de Imagen Asistido por Computador , Ratones , UltrasonografíaRESUMEN
Thermal ablation by high-intensity focused ultrasound (HIFU) shows great promise as a noninvasive cancer therapy. This work proposes a novel method of real-time HIFU treatment monitoring that uses the passively monitored acoustic signal emanating from the focus during HIFU exposure. We performed 212 exposures in seven freshly excised ox livers using 1.067-MHz HIFU at a 95% duty cycle for a range of insonation durations and acoustic intensities. Acoustic emissions were recorded using a 15-MHz passive detector aligned confocally and coaxially with the HIFU transducer. Lesion presence and size were ascertained by slicing the tissue in the transverse and axial focal planes post exposure. Our results demonstrate that successful formation of HIFU lesions in ex vivo ox liver is highly correlated with the presence of pronounced dips in the magnitude of the received signal at integer harmonics of the insonation frequency. A detector based on this observation predicted lesioning with >80% accuracy in regimes that were very likely to create lesions (≥60 J of energy) and had an error rate of <6% for exposures that were too short to cause lesioning (≤1 s long). The overall sensitivity and specificity of the detector were 75.6% and 74.2%, respectively. The proposed detector could therefore provide a low-cost means of effectively monitoring clinical HIFU treatments passively and in real time.
Asunto(s)
Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Hígado/diagnóstico por imagen , Hígado/cirugía , Cirugía Asistida por Computador/métodos , Ultrasonografía/métodos , Animales , Bovinos , Técnicas In Vitro , MasculinoRESUMEN
PURPOSE: In controlled laboratory studies of hyperthermia and thermal ablation, translucent hydrogels containing bovine serum albumin (BSA) are often employed as tissue-mimicking materials due to the change in their opacity that takes place as they accumulate heat damage. In this work we demonstrate the biological relevance of this optical metric of thermal damage, as well as establish the physical mechanisms that link it with quantifiable damage to the proteins embedded in the gel. MATERIALS AND METHODS: We applied Fourier transform infrared (FTIR) spectroscopy, turbidity analysis using ultraviolet-visible (UV/VIS) spectroscopy, and size exclusion chromatography (SEC) to samples of heat-treated, aqueous bovine serum albumin (BSA). We also measured the rates of survival in heated suspensions of breast cancer cells using a colorimetric assay. RESULTS: Using FTIR spectroscopy and SEC, we show that the intermolecular beta-sheet content of the protein ensemble rises in heat treatments above 60 degrees C, which causes aggregate formation. Furthermore, by applying UV/VIS spectroscopy we demonstrate that the opacity of the hydrogel increases past 60 degrees C due to the formation of insoluble protein aggregates that scatter incident light. Finally, we illustrate that the viability of human breast cancer cells follows a similar trend to measurements of BSA polyacrylamide hydrogel opacity at various temperatures from 37 degrees C to 90 degrees C. CONCLUSIONS: Our work establishes a causal link between the degree of BSA denaturation in hydrogel and the opacity of the medium. Furthermore, our results demonstrate that BSA hydrogels provide a simple physical model for quantifying biologically relevant heat damage in real time during controlled laboratory studies of hyperthermia and thermal ablation.