Insights from echocardiography, magnetic resonance imaging, and microcomputed tomography relative to the mid-myocardial left ventricular echogenic zone.

Background: The anatomical substrate for the mid-mural ventricular hyperechogenic zone remains uncertain, but it may represent no more than ultrasound reflected from cardiomyocytes orientated orthogonally to the ultrasonic beam. We sought to ascertain the relationship between the echogenic zone and the orientation of the cardiomyocytes. Methods: We used 3D echocardiography, diffusion tensor imaging, and microcomputed tomography to analyze the location and orientation of cardiomyocytes within the echogenic zone. Results: We demonstrated that visualization of the echogenic zone is dependent on the position of the transducer and is most clearly seen from the apical window. Diffusion tensor imaging and microcomputed tomography show that the echogenic zone seen from the apical window corresponds to the position of the circumferentially orientated cardiomyocytes. An oblique band seen in the parasternal view relates to cardiomyocytes orientated orthogonally to the ultrasonic beam. Conclusions: The mid-mural ventricular hyperechogenic zone represents reflected ultrasound from cardiomyocytes aligned orthogonal to the ultrasonic beam. The echogenic zone does not represent a space, a connective tissue sheet, a boundary between ascending and descending limbs of a hypothetical helical ventricular myocardial band, nor an abrupt change in cardiomyocyte orientation

Insights from echocardiography, magnetic resonance imaging, and microcomputed tomography relative to the mid-myocardial left ventricular echogenic zone.

BACKGROUND: The anatomical substrate for the mid-mural ventricular hyperechogenic zone remains uncertain, but it may represent no more than ultrasound reflected from cardiomyocytes orientated orthogonally to the ultrasonic beam. We sought to ascertain the relationship between the echogenic zone and the orientation of the cardiomyocytes. METHODS: We used 3D echocardiography, diffusion tensor imaging, and microcomputed tomography to analyze the location and orientation of cardiomyocytes within the echogenic zone. RESULTS: We demonstrated that visualization of the echogenic zone is dependent on the position of the transducer and is most clearly seen from the apical window. Diffusion tensor imaging and microcomputed tomography show that the echogenic zone seen from the apical window corresponds to the position of the circumferentially orientated cardiomyocytes. An oblique band seen in the parasternal view relates to cardiomyocytes orientated orthogonally to the ultrasonic beam. CONCLUSIONS: The mid-mural ventricular hyperechogenic zone represents reflected ultrasound from cardiomyocytes aligned orthogonal to the ultrasonic beam. The echogenic zone does not represent a space, a connective tissue sheet, a boundary between ascending and descending limbs of a hypothetical helical ventricular myocardial band, nor an abrupt change in cardiomyocyte orientation

Assessment of the Helical Ventricular Myocardial Band Using Standard Echocardiography

n the discussion of their recent article, Hayabuchi and his colleagues[1] acknowledge that the “helical myocardial band” remains controversial. In the accompanying editorial, Buckberg harbored no such doubts.[2] Are the limited echocardiographic findings illustrated truly sufficient for Hayabuchi and his colleagues to conclude that there is a “helical ventricular myocardial band”?[1] They refer to a model that Torrent-Guasp had carved out of the ventricular muscular mass by disrupting myriads of myocardial branches, suggesting moreover that this band is freely moveable on itself. The histological studies produced by Hort[3] and Feneis,[4] however, provided evidence that the ventricular cone does not have discrete origins and insertions of the cardiomyocytes as found in skeletal muscle. Pettigrew had demonstrated more than a century ago[5] the multiple interleaving sheets of cardiomyocytes to be found within the cone. Lev and Simkins,[6] cited by Buckberg, also had emphasized that the cone can be dissected at the whim of the prosector, as achieved by Torrent-Guasp when subjectively producing the preparations now modeled by Buckberg.[7] Our investigations, cited by Hayabuchi and colleagues,[1] endorse the works of Feneis[3] and Hort.[4] The histological findings show no obvious anatomical substrate, other than the obvious change in alignment of the aggregated chains of cardiomyocytes, to explain the echocardiographic feature emphasized by the Japanese workers. They certainly provide none that represent a substantial proportion of the width of the septum, as the echocardiograms seem to suggest. The echogenic band is seen in the equatorial and basal regions of each of the walls of the left ventricle when viewed from the apex. No such band is seen when the ventricular mass is viewed using the parasternal window. We suggest that the echogenic band represents an area of distinct myocyte orientation within the continuous mesh of the septum, where the reflected ultrasound is perpendicular to the dominant orientation of the cardiomyocytes, thus giving maximum intensity compared with the surrounding tissue. The echogenic band, when viewed from the apex, therefore, is likely to represent no more than the chains of cardiomyocytes located within the mid-wall of the ventricular cone which are aligned circumferentially. The concept of the helical ventricular myocardial band does not model the circumferential orientation in this region. There are further problems, however, with the concepts advanced by Buckberg,[2] His inferences are based on imaging systems that measure only strain, as opposed to assessing the local development of force. The onset of shortening is not identical with the onset of contraction, so it is his mistake to interpret late shortening as delayed contraction. We have shown that within the ventricular cone, there are extended zones in which the myocardium contracts auxotonically, that is, the force increases during systole.[8] The features of such auxotonic contraction are delayed onset, restricted shortening, and delayed termination

Dominant Splice Site Mutations in PIK3R1 Cause Hyper IgM Syndrome, Lymphadenopathy and Short Stature.

The purpose of this research was to use next generation sequencing to identify mutations in patients with primary immunodeficiency diseases whose pathogenic gene mutations had not been identified. Remarkably, four unrelated patients were found by next generation sequencing to have the same heterozygous mutation in an essential donor splice site of PIK3R1 (NM_181523.2:c.1425 + 1G > A) found in three prior reports. All four had the Hyper IgM syndrome, lymphadenopathy and short stature, and one also had SHORT syndrome. They were investigated with in vitro immune studies, RT-PCR, and immunoblotting studies of the mutation's effect on mTOR pathway signaling. All patients had very low percentages of memory B cells and class-switched memory B cells and reduced numbers of naïve CD4+ and CD8+ T cells. RT-PCR confirmed the presence of both an abnormal 273 base-pair (bp) size and a normal 399 bp size band in the patient and only the normal band was present in the parents. Following anti-CD40 stimulation, patient's EBV-B cells displayed higher levels of S6 phosphorylation (mTOR complex 1 dependent event), Akt phosphorylation at serine 473 (mTOR complex 2 dependent event), and Akt phosphorylation at threonine 308 (PI3K/PDK1 dependent event) than controls, suggesting elevated mTOR signaling downstream of CD40. These observations suggest that amino acids 435-474 in PIK3R1 are important for its stability and also its ability to restrain PI3K activity. Deletion of Exon 11 leads to constitutive activation of PI3K signaling. This is the first report of this mutation and immunologic abnormalities in SHORT syndrome