Using optoacoustic imaging for measuring the temperature dependence of Grüneisen parameter in optically absorbing solutions.

Grüneisen parameter is a key temperature-dependent physical characteristic responsible for thermoelastic efficiency of materials. We propose a new methodology for accurate measurements of temperature dependence of Grüneisen parameter in optically absorbing solutions. We use two-dimensional optoacoustic (OA) imaging to improve accuracy of measurements. Our approach eliminates contribution of local optical fluence and absorbance. To validate the proposed methodology, we studied temperature dependence of aqueous cupric sulfate solutions in the range from 22 to 4 °C. Our results for the most diluted salt perfectly matched known temperature dependence for the Grüneisen parameter of water. We also found that Grüneisen-temperature relationship for cupric sulfate exhibits linear trend with respect to the concentration. In addition to accurate measurements of Grüneisen changes with temperature, the developed technique provides a basis for future high precision OA temperature monitoring in live tissues.

How accurately, reproducibly, and efficiently can we measure left ventricular indices using M-mode, 2-dimensional, and 3-dimensional echocardiography in children?

BACKGROUND: Measurements of left ventricular (LV) size, mass, and function are the most common and important tasks for echocardiography in clinical practice and research in children with congenital and acquired heart diseases. There are little data to compare the utility of M-mode (MM), 2-dimensional (2D), and 3-dimensional (3D) echocardiographic techniques for quantification of LV indices. The objective of the study was to assess the accuracy, reproducibility, and efficiency of these echocardiographic methods for measurement of LV indices in children. METHODS: A prospective study was conducted in 20 consecutive children (mean 10.6 +/- 2.8 years, 11 male and 9 female subjects) using conventional MM, 2D, and real-time 3D echocardiography (RT3DE). A Sonos 7500 system (Philips Medical Systems, Andover, MA) was used. M-mode and 2DE measurements were made according to the American Society of echocardiography recommendations. To include the entire LV for volumetric measurement, full-volume 3D data sets were acquired from 4 electrocardiogram gated subvolumes. The 3DE measurements were made off-line manually using 4-plane and 8-plane algorithms by 4D Echo-View (TomTec Imaging Systems, Munich, Germany) and a semiautomated algorithm by QLAB (Philips Medical Systems). Magnetic resonance imaging studies were also performed to determine the LV indices by a disk summation method based on the Simpson principle. RESULTS: The correlation and agreement between MM, 2D, and RT3D echocardiography and magnetic resonance imaging measurements are good (r = 0.81-0.97) for the 3 methods. The correlation was superior for RT3DE compared with 2DE and MM. The correlation and agreement were similar for the three 3DE methods. The intra- and interobserver variabilities ranged from MM (4.3%-4.8% and 7.0%-8.7%), 2DE (3.3%-4.5% and 5.5%-7.3%), and 3DE (0.4%-2.3%, and 0.2%-4.8%). The total time (acquisition and analysis) used for MM measurements was the least compared with 2DE and 3DE. The total time for 3DE using the semiautomated algorithms was not significantly different compared with that for 2DE. CONCLUSIONS: Our study showed that MM provides the most efficient assessment of LV indices but is the least accurate and reproducible technique compared with 2DE and 3DE. Three-dimensional echocardiography using both automated and manual analysis algorithm is superior to MM and 2DE for measurements of LV indices, and the automated 3DE algorithm is as efficient as 2DE. Therefore, 3DE using the automated algorithm is the method of choice for quantification of LV indices.

Desmosomal dysfunction due to mutations in desmoplakin causes arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by progressive degeneration of the right ventricular myocardium, ventricular arrhythmias, fibrous-fatty replacement, and increased risk of sudden death. Mutations in 6 genes, including 4 encoding desmosomal proteins (Junctional plakoglobin (JUP), Desmoplakin (DSP), Plakophilin 2, and Desmoglein 2), have been identified in patients with ARVD/C. Mutation analysis of 66 probands identified 4 variants in DSP; V30M, Q90R, W233X, and R2834H. To establish a cause and effect relationship between those DSP missense mutations and ARVD/C, we performed in vitro and in vivo analyses of the mutated proteins. Unlike wild-type (WT) DSP, the N-terminal mutants (V30M and Q90R) failed to localize to the cell membrane in desomosome-forming cell line and failed to bind to and coimmunoprecipitate JUP. Multiple attempts to generate N-terminal DSP (V30M and Q90R) cardiac-specific transgenes have failed: analysis of embryos revealed evidence of profound ventricular dilation, which likely resulted in embryonic lethality. We were able to develop transgenic (Tg) mice with cardiac-restricted overexpression of the C-terminal mutant (R2834H) or WT DSP. Whereas mice overexpressing WT DSP had no detectable histologic, morphological, or functional cardiac changes, the R2834H-Tg mice had increased cardiomyocyte apoptosis, cardiac fibrosis, and lipid accumulation, along with ventricular enlargement and cardiac dysfunction in both ventricles. These mice also displayed interruption of DSP-desmin interaction at intercalated discs (IDs) and marked ultra-structural changes of IDs. These data suggest DSP expression in cardiomyocytes is crucial for maintaining cardiac tissue integrity, and DSP abnormalities result in ARVD/C by cardiomyocyte death, changes in lipid metabolism, and defects in cardiac development.

Imaging technique for real-time temperature monitoring during cryotherapy of lesions.

Noninvasive real-time temperature imaging during thermal therapies is able to significantly improve clinical outcomes. An optoacoustic (OA) temperature monitoring method is proposed for noninvasive real-time thermometry of vascularized tissue during cryotherapy. The universal temperature-dependent optoacoustic response (ThOR) of red blood cells (RBCs) is employed to convert reconstructed OA images to temperature maps. To obtain the temperature calibration curve for intensity-normalized OA images, we measured ThOR of 10 porcine blood samples in the range of temperatures from 40°C to ?16°C and analyzed the data for single measurement variations. The nonlinearity (?Tmax) and the temperature of zero OA response (T0) of the calibration curve were found equal to 11.4±0.1°C and ?13.8±0.1°C, respectively. The morphology of RBCs was examined before and after the data collection confirming cellular integrity and intracellular compartmentalization of hemoglobin. For temperatures below 0°C, which are of particular interest for cryotherapy, the accuracy of a single temperature measurement was ±1°C, which is consistent with the clinical requirements. Validation of the proposed OA temperature imaging technique was performed for slow and fast cooling of blood samples embedded in tissue-mimicking phantoms.

Accuracy and reproducibility of real-time three-dimensional echocardiography for assessment of right ventricular volumes and ejection fraction in children.

BACKGROUND: Measurement of right ventricular (RV) volumes and ejection fraction (EF) by two-dimensional echocardiography has limited accuracy and reproducibility because of the complex RV geometry. OBJECTIVES: This study sought to validate real-time three-dimensional echocardiography (RT3DE) using a disk summation method for assessment of RV volumes and RVEF in children by comparing it with magnetic resonance imaging (MRI) measurements. METHODS: A total of 20 children (mean age 10.6 +/- 2.8 years) were studied. Transthoracic RT3DE was performed using a RT3DE system to acquire full-volume RT3DE data sets from apical windows and data were processed offline using a software package. RV end-systolic volume and end-diastolic volume (EDV) were measured using a disk summation method by manually tracing the endocardial borders. RVEF was calculated as: RVEF = (EDV - end-systolic volume)/EDV x 100%. All participants also underwent MRI studies for comparison of RV indexes. RESULTS: Of the 20 children, 3 were excluded because of poor or incomplete RV images (two RT3DE and one MRI study). For the remaining 17 children, good correlation and agreement between RT3DE and MRI were found (RVEDV: r = 0.98, P < .001, mean difference = -7.0 +/- 9.0 mL, P < .01; RV end-systolic volume: r = 0.96, P < .001, mean difference = -3.2 +/- 7.1 mL, P > .05; RVEF: r = 0.89, P < .001, mean difference = -0.3 +/- 7.1%, P > .05). The intraobserver and the interobserver variabilities ranged from -1.1% to 5.8%. CONCLUSION: Measurement of RV volumes and EF by RT3DE is feasible, accurate, and reproducible in children compared with MRI measurements.

Measurement of volumetric flow by real-time 3-dimensional doppler echocardiography in children.

BACKGROUND: We sought to assess the accuracy and reproducibility of an automated real-time (RT) 3-dimensional (3D) Doppler echocardiography (RT3DDE) technique for measuring volumetric flow (VF) in children. METHODS: A total of 19 healthy children (age = 11.5 +/- 3.5 years) were studied to measure VF through mitral valve (MV), aortic valve (AV), pulmonary valve (PV), and tricuspid valve (TV) by RT3DDE. RT 3D echocardiography was also performed to measure left ventricular (LV) end-systolic volume, LV end-diastolic volume, and stroke volume (stroke volume = LV end-diastolic volume--LV end-systolic volume), which served as a reference standard for comparison with VF by RT3DDE. RESULTS: Compared with stroke volume by RT 3D echocardiography, the correlation with VF was excellent for MV (r = 0.91), good for AV (r = 0.89) and PV (r = 0.89), but poor for TV (r = 0.20) by RT3DDE. There were good agreements for AV (bias = 0.9 +/- 5.0 mL), PV (bias = -0.4 +/- 5.7 mL), and MV (bias = 4.1 +/- 4.7 mL), and marked underestimation for TV (bias = -24.4 +/- 14.6 mL). CONCLUSIONS: Our data demonstrated that VF measurement by RT3DDE is feasible and reasonably accurate for MV, AV, and PV but problematic for TV.