Combined flow-based imaging assessment of optimal cardiac resynchronization therapy pacing vector: a case report.

BACKGROUND: There are still many pendent issues about the effective evaluation of cardiac resynchronization therapy impact on functional mitral regurgitation. In order to reduce the intrinsic difficulties of quantification of functional mitral regurgitation itself, an automatic quantification of real-time three-dimensional full-volume color Doppler transthoracic echocardiography was proposed as a new, rapid, and accurate method for the assessment of functional mitral regurgitation severity. Recent studies suggested that images of left ventricle flow by echo-particle imaging velocimetry could be a useful marker of synchrony. Echo-particle imaging velocimetry has shown that regional anomalies of synchrony/synergy of the left ventricle are related to the alteration, reduction, or suppression of the physiological intracavitary pressure gradients. We describe a case in which the two technologies are used in combination during acute echocardiographic optimization of left pacing vector in a 63-year-old man, Caucasian, who showed worsening heart failure symptoms a few days after an implant, and the effect of the device's optimization at 6-month follow-up. DISCUSSION: The degree of realignment of hemodynamic forces, with quantitative analysis of the orientation of blood flow momentum (φ), can represent improvement of fluid dynamics synchrony of the left ventricle, and explain, with a new deterministic parameter, the effects of cardiac resynchronization therapy on functional mitral regurgitation. Real-time three-dimensional color flow Doppler quantification is feasible and accurate for measurement of mitral inflow, left ventricular outflow stroke volumes, and functional mitral regurgitation severity. CONCLUSION: This clinical case offers an innovative and accurate approach for acute echocardiographic optimization of left pacing vector. It shows clinical utility of combined three-dimensional full-volume color Doppler transthoracic echocardiography/echo-particle imaging velocimetry assessment to increase response to cardiac resynchronization therapy, in terms of reduction of functional mitral regurgitation, improving fluid dynamics synchrony of the left ventricle.

STRAIN ANALYSIS OF MASSETER MUSCLE BY ULTRASOUND.

The masseter muscle represents an area of important functional interest. The present study aims to verify the feasibility of ultrasound imaging for quantifying the muscular deformation pattern in the masseter. Fifteen consecutive subjects were enrolled and underwent masseter ultrasound according to a repeatable protocol. Ultrasound was carried out during teeth clenching in natural conditions and after the insertion of a medical device that alters the distance between the dental arches, and was repeated on 3 different days. Results showed that masseter deformation is not uniform within the muscle. The same strain patterns were repeated in the different ultrasounds of the same patient and were modified after the introduction of a medical device. This was supported by quantitative comparisons in the deep portion of the muscle (standard deviation on the three measures: 3% normal conditions, 2% with medical device) showing a systematic reduction with the prosthesis (30% on average). This study demonstrated that masseter strain analysis is a repeatable and sensitive tool for the study of functional analysis of the masticatory organ. This opens new technical perspectives for the diagnosis and therapy of dysfunctional pathologies of the masticatory organ.

Quantitative analysis of intraventricular blood flow dynamics by echocardiographic particle image velocimetry in patients with acute myocardial infarction at different stages of left ventricular dysfunction.

AIMS: Left ventricular (LV) diastolic filling is characterized by the formation of a vortex that supports an efficient transit into systolic ejection. Aim of this study was to assess the intraventricular (IV) blood flow dynamics among patients with ST elevated myocardial infarction (STEMI) at different degrees of LV dysfunction, in the attempt to find novel indicators of LV pump efficiency. METHODS AND RESULTS: Sixty-four subjects, 34 consecutive STEMI patients and 30 healthy controls, underwent before hospital discharge 2D speckle tracking echocardiography to assess global longitudinal strain (GLS), and echo-particle image velocimetry analysis to assess flow energetic parameters. Left ventricular volumes ejection fraction (LVEF) and global wall motion score index (GWMSI) were evaluated by 3D echocardiography. ST elevated myocardial infarction patients were subdivided into three groups according to LVEF. Energy dissipation, vorticity fluctuation, and kinetic energy fluctuation indexes, which characterize the degree of disturbance in the flow, exhibit a biphasic behaviour in STEMI patients when compared with controls, with the highest values in patients with still preserved LV function and progressive lower values with LV function worsening. Significant linear correlations were found between energy dissipation index and both LVEF and GLS (r = 0.57, P < 0.001 and r = -0.61, P = 0.001, respectively). Kinetic energy fluctuation index significantly correlates with both LVEF (r = 0.75, P < 0.001) and GLS (-0.58, P = 0.002). Finally, a significant correlation was observed between GWMSI and energy dissipation index (-0.56, P = 0.008). CONCLUSIONS: The present study describes, for the first time, the progression of IV flow energetic properties in patients with acute myocardial infarction at different stages of LV dysfunction when compared with healthy controls. Further data are needed to assess the role of these parameters in the development and maintenance of LV dysfunction.

Zymographic analysis and characterization of MMP-2 and -9 forms in human sound dentin.

The role and function of dentin matrix metalloproteinases (MMPs) are not well-understood, but they may play a key role in dentinal caries and the degradation of resin-bonded dentin matrices. To test the null hypothesis that MMP-9 is not found in dentin matrix, we used gelatin zymography to extract and isolate all molecular forms of gelatinolytic MMPs in demineralized mature sound dentin powder obtained from extracted human molars, characterizing and identifying the enzymes by Western blotting. Gelatinolytic MMPs were detected in extracts of demineralized dentin matrix and identified as MMP-2 and MMP-9. Acidic extracts (pH 2.3) yielded 3-8 times more MMP activity than did EDTA (pH 7.4). Their activation may contribute to dentin matrix degradation, which occurs during caries progression and following resin bonding. Inhibition of MMP-2 and -9 proteolytic activity may slow caries progression and increase the durability of resin-dentin bonds.

Myocardial systolic strain abnormalities in patients with acromegaly: a prospective color Doppler imaging study.

BACKGROUND: Heart abnormalities are frequent findings in patients with acromegaly: systolic abnormalities are considered to be secondary to diastolic changes. AIM: The aim of the study was to evaluate whether early systolic abnormalities might be revealed in acromegalic patients using the high sensitive color Doppler myocardial imaging (CDMI) technique. PATIENTS AND METHODS: Twenty-two consecutive acromegalic patients with active untreated disease (ACROUNTR) were evaluated at baseline and after a 6-month course with SS analogs (SSa) (ACROSSa); 25 healthy subjects served as controls. All subjects underwent conventional 2D-color Doppler echocardiography, pulse wave tissue Doppler imaging (PW-TDI) and CDMI. RESULTS: Mean left ventricular (LV) ejection fraction did not differ in ACROUNTR and in controls; at variance, ACROUNTR patients had reduced mean LV diastolic function (E/A ratio: 0.96+/-0.3 vs controls: 1.6+/-0.3; p<0.002). Impairment of global LV diastolic function was confirmed by PW-TDI in ACROUNTR patients having a normal systolic function. Regional myocardial systolic strain (epsilon) and strain rate (SR) values, indices of regional systolic heart deformation, were lower in ACROUNTR [epsilonsys (S) -19.8+/-2.9 and epsilonsys (L): -17.7+/-2.2] than in controls [epsilonsys (S): -27.9+/-3.8; p<0.001 and epsilonsys (L): -25.3+/-2.6; p<0.001]. In addition, the early phase of diastolic function, evaluated using SR parameters, was impaired in acromegalic patients (p<0.005 vs controls). Strain and SR values were related to serum GH and IGF-I levels (p<0.02) and greatly improved after a 6-month course with SSa [epsilonsys (S) improved to -23.8+/-3.8 (p<0.05) and epsilonsys (L) improved to -24.7+/-2.4 (p<0.03)]. CONCLUSIONS: Our study confirms that ACROUNTR patients have impaired diastolic function. More important, our study clearly shows that ACROUNTR patients have an impairment of regional myocardial systolic function, which is not secondary to diastolic changes. These intramyocardial functional abnormalities improved during medical treatment of acromegaly. It is conceivable that GH-IGF-I excess has detrimental effects either on the diastolic or the systolic phases of heart function.

Quantification methods in contrast echocardiography.

New technologies and the availability of new echo-contrast agents have resulted in advances of diagnostic and prognostic indications of left ventricular opacification (LVO) and myocardial perfusion. The clinical diagnostic value of ultrasound contrast media for LVO and its impact on the clinical decision-making process has been demonstrated in several studies. Recent research aims at developing new quantitative software to improve the delineation of the endocardial border, to assess 3D myocardial perfusion for more accurate regional/global LV function measurements, and to evaluate 4D intra-cardiac flow dynamics. Furthermore, a general consensus has been reached on the incremental value of myocardial contrast echocardiography (MCE) for obtaining additional information in both chronic and acute coronary artery disease (CAD) patients and on the possibility to make quantitative measurements of microvascular damage. Q-contrast is a new software system which provides quantitative measurements to generate parametric images of microcirculatory flow. In a research project including 120 patients, Q-contrast software has been tested to assess the role of contrast in AMI (Acute Myocardial Infarction Contrast Imaging (A.M.I.C.I. Study); good agreement between parametric MCE and SPECT has been found. Preliminary results further confirm that quantitative MCE may provide additional clinical value over qualitative information for the assessment of LV function and of the effects of coronary artery disease on the myocardial microcirculation (viability, ischemia or infarct).

Matrix metalloproteinase inhibitors as anticancer therapeutics.

Matrix metalloproteinases (MMPs), also designated as matrixins, play a central role in many biological processes and are involved both in physiologic cellular processes and in pathologic situations such as tumor growth, invasion and metastasis. For more than 30 years MMPs have been considered as promising targets for cancer therapy and a number of different synthetic and natural MMP inhibitors have been identified as cytostatic and anti-angiogenic agents and have begun clinical testing in view of their specific implication in malignant tissues. Although preclinical studies were so compelling to encourage several clinical trials, the past years have seen a consistent number of disappointments and limited success. The critical examination of previous studies shed light on new information about the cellular source, substrates and mode of action of MMPs, focusing the attention of future research on the identification of specific MMP targets in tumors at different stage of tumor progression, both in order to improve efficacy and to reduce the side effect profile. In this review we discuss the current view on the feasibility of MMPs as target for therapeutic intervention in cancer, taking into account that the perspective may be of great value for molecular medicine for the twenty-first century, providing intriguing information about the MMPs as mediators in biology and pathology, and as targets for disease therapies.

New insights into regional systolic and diastolic left ventricular function with tissue Doppler echocardiography: from qualitative analysis to a quantitative approach.

Tissue Doppler echocardiography is a variation of conventional Doppler flow imaging. This modality allows quantification of the Doppler shift within the range of myocardial tissue motion. The velocity at a variety of myocardial sites can be determined and distinguished very rapidly by using Doppler techniques. The velocity of moving tissue can be studied with pulsed wave tissue Doppler sampling, which displays the velocity of a selected myocardial region against time, with high temporal resolution. In addition, the velocities can be calculated with time-velocity maps and displayed as color-encoded velocity maps in either an M-mode or 2-dimensional format. This review will focus on the technical aspects and the different methods of tissue Doppler echocardiography for the analysis of regional systolic and diastolic left ventricular function. Whereas pulsed wave tissue Doppler echocardiography allows measurements of velocities of a selected myocardial region, color tissue Doppler gives the best overview of cardiac dynamics because the entire scanned color data are displayed simultaneously. However, there is an increasing need for objective evaluation of tissue Doppler information. Digital images and postprocessing of the data allow for quantitative off-line analysis, and the different approaches and parameters proposed from different centers are discussed.

From digital image processing of colour Doppler M-mode maps to noninvasive evaluation of the left ventricular diastolic function: a dedicated software package.

Noninvasive estimation of diastolic pressure gradients has recently been validated using the space-temporal velocity distribution available from colour Doppler M-mode (CDM). However, the methods currently applied for analysing CDM patterns of left ventricular (LV) filling have limitations, such as lack of automation, subjective variability and limited use of digital velocity map. For this reason, we have developed software able to acquire and process the CDM maps; thus, providing an easily interpretable graphical and numerical display. The pressure field is obtained by approximating the derivatives with centred finite differences via the incompressible Navier-Stokes equations. After digital filtering of the noise and the removal of the colour black spots, the velocity field is utilised to compute the pressure gradient field and the pressure values by spatial integration. It is concluded that automatic quantification of colour CDM patterns is feasible and will be a strategic tool in the investigation of one of the most intriguing topics in cardiology.

[Tissue Doppler: the physical principles, representational and analytical modalities and clinical applications]. / Il Doppler tessutale: principi fisici, modalità di rappresentazione e di analisi ed applicazioni cliniche.

Tissue Doppler imaging or myocardial velocity imaging is a variation of conventional Doppler. This modality allows the quantification of the Doppler shift within the range of myocardial tissue motion. The velocity of motion at a variety of myocardial sites can be determined and distinguished very rapidly using Doppler techniques. The velocity of moving tissue can be studied with pulsed wave tissue Doppler sampling, which displays the velocity of a selected myocardial region against time, with high temporal resolution. In addition, the velocities can be calculated with time velocity maps and displayed as color coded velocity maps in either M-mode or two-dimensional format. This review will focus on the technical aspects and the different methods of tissue Doppler for regional systolic and diastolic left ventricular function analysis. While pulsed wave tissue Doppler allows us to measure the velocities of a selected myocardial region, color tissue Doppler gives the best overall view of cardiac dynamics because the whole scanned color data are displayed simultaneously. However, there is an increasing need for objective evaluation of tissue Doppler information. Digital images and data post-processing allow for quantitative off-line analysis, and the different approaches and parameters proposed from different centers are discussed. In recent years, tissue Doppler imaging has been applied for accurate evaluation of diastolic function, quantifying regional function particularly during stress, pre-excitation syndrome, and left ventricular hypertrophy. The results of these experiences indicate that tissue Doppler imaging is a promising technique for quantifying the response of the myocardium and endocardium during both normal and abnormal function. Again, there is a significant learning curve concerning its application, but with experience it will be a useful and reproducible technique.