This article presents a new method for measuring longitudinal strain in a short-axis section of the heart using harmonic phase magnetic resonance imaging (HARP-MRI). The heart is tagged using 1-1 SPAMM at end-diastole with tag surfaces parallel to a short-axis imaging plane. Two or more images are acquired such that the images have different phase encodings in a direction orthogonal to the image plane. A dense map of the longitudinal strain can be computed from these images using a simple, fast computation.

Copy number variants (CNVs) and intragenic rearrangements of the NRXN1 (neurexin 1) gene are associated with a wide spectrum of developmental and neuropsychiatric disorders, including intellectual disability, speech delay, autism spectrum disorders (ASDs), hypotonia and schizophrenia. We performed a detailed clinical and molecular characterization of 24 patients who underwent clinical microarray analysis and had intragenic deletions of NRXN1. Seventeen of these deletions involved exons of NRXN1, whereas seven deleted intronic sequences only. The patients with exonic deletions manifested developmental delay/intellectual disability (93%), infantile hypotonia (59%) and ASDs (56%). Congenital malformations and dysmorphic features appeared infrequently and inconsistently among this population of patients with NRXN1 deletions. The more C-terminal deletions, including those affecting the b isoform of neurexin 1, manifested increased head size and a high frequency of seizure disorder (88%) when compared with N-terminal deletions of NRXN1.

SUMMARYUsher syndrome is the most prevalent cause of hereditary deaf-blindness, characterized by congenital sensorineural hearing impairment and progressive photoreceptor degeneration beginning in childhood or adolescence. Diagnosis and management of this disease are complex, and the molecular changes underlying sensory cell impairment remain poorly understood. Here we characterize two zebrafish models for a severe form of Usher syndrome, Usher syndrome type 1C (USH1C): one model is a mutant with a newly identified ush1c nonsense mutation, and the other is a morpholino knockdown of ush1c. Both have defects in hearing, balance and visual function from the first week of life. Histological analyses reveal specific defects in sensory cell structure that are consistent with these behavioral phenotypes and could implicate Müller glia in the retinal pathology of Usher syndrome. This study shows that visual defects associated with loss of ush1c function in zebrafish can be detected from the onset of vision, and thus could be applicable to early diagnosis for USH1C patients.

The harmonic phase (HARP) method provides automatic and rapid analysis of tagged magnetic resonance (MR) images for quantification and visualization of myocardial strain. In this article, the development and implementation of a pulse sequence that acquires HARP images in real time are described. In this pulse sequence, a CINE sequence of images with 1-1 spatial modulation of magnetization (SPAMM) tags are acquired during each cardiac cycle, alternating between vertical and horizontal tags in successive heartbeats. An incrementing train of imaging RF flip angles is used to compensate for the decay of the harmonic peaks due to both T 1 relaxation and the applied imaging pulses. The magnitude images displaying coarse anatomy are automatically reconstructed and displayed in real time after each heartbeat. HARP strain images are generated offline at a rate of four images per second; real-time processing should be possible with faster algorithms or computers. A comparison of myocardial contractility in non-breath-hold and breath-hold experiments in normal humans is presented.

Background-Because ECG alterations caused by ischemia cannot be reliably detected in the high-field MRI environment, detection of wall motion abnormalities is often used to ensure patient safety during stress testing. However, an experienced observer is needed to detect these abnormalities. In this study, we investigate the use of fast harmonic phase (FastHARP) MRI for the quantitative, operator-independent detection of the onset of ischemia during acute coronary occlusion. Methods and Results-Eight mongrel dogs underwent an acute 2-minute closed-chest coronary artery occlusion while continuous FastHARP images were acquired. Full regional wall strain was determined every other heartbeat in a single short-axis imaging slice. After 5 minutes of reperfusion, a second 2-minute ischemic episode was induced during the acquisition of conventional cine wall-motion images. The time at which ECG alterations were observed during the first ischemic period was recorded. The time from occlusion to the detection of ischemia, based on a consensus of 2 blinded observers, was determined for MRI. No significant ischemia was present in 2 animals. In the remaining animals, the onset of ischemia was detected significantly earlier by FastHARP than by cine MRI (9.5Ϯ5 versus 33Ϯ14 seconds, PϽ0.01). HARP ischemia detection preceded ECG changes, on average, by 54 seconds. Conclusions-The rapid acquisition and detection of induced ischemia with FastHARP MRI shows promise as a nonsubjective method to diagnose significant coronary lesions during MR stress testing.