Single breath-hold slice-following CSPAMM myocardial tagging

Myocardial tagging has shown to be a useful magnetic resonance modality for the assessment and quantification of local myocardial function. Many myocardial tagging techniques suffer from a rapid fading of the tags, restricting their application mainly to systolic phases of the cardiac cycle. However, left ventricular diastolic dysfunction has been increasingly appreciated as a major cause of heart failure. Subtraction based slice-following CSPAMM myocardial tagging has shown to overcome limitations such as fading of the tags. Remaining impediments, to this technique, however, are extensive scanning times (∼10 min), the requirement of repeated breath-holds using a coached breathing pattern, and the enhanced sensitivity of artifacts related to poor patient compliance or inconsistent depths of end-expiratory breath-holds. We therefore propose a combination of slice-following CSPAMM myocardial tagging with a segmented EPI imaging sequence. Together with an optimized RF excitation scheme, this enables to acquire as many as 20 systolic and diastolic grid-tagged images per cardiac cycle with a high tagging contrast during a short period of sustained respiratio

Coronary MR angiography at 3T: fat suppression versus water-fat separation

Objectives: To compare Dixon water-fat suppression with spectral pre-saturation with inversion recovery (SPIR) at 3T for coronary magnetic resonance angiography (MRA) and to demonstrate the feasibility of fat suppressed coronary MRA at 3T without administration of a contrast agent. Materials and methods: Coronary MRA with Dixon water-fat separation or with SPIR fat suppression was compared on a 3T scanner equipped with a 32-channel cardiac receiver coil. Eight healthy volunteers were examined. Contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), right coronary artery (RCA), and left anterior descending (LAD) coronary artery sharpness and length were measured and statistically compared. Two experienced cardiologists graded the visual image quality of reformatted Dixon and SPIR images (1: poor quality to 5: excellent quality). Results: Coronary MRA images in healthy volunteers showed improved contrast with the Dixon technique compared to SPIR (CNR blood-fat: Dixon = 14.9 ± 2.9 and SPIR = 13.9 ± 2.1; p = 0.08, CNR blood-myocardium: Dixon = 10.2 ± 2.7 and SPIR = 9.11 ± 2.6; p = 0.1). The Dixon method led to similar fat suppression (fat SNR with Dixon: 2.1 ± 0.5 vs. SPIR: 2.4 ± 1.2, p = 0.3), but resulted in significantly increased SNR of blood (blood SNR with Dixon: 19.9 ± 4.5 vs. SPIR: 15.5 ± 3.1, p < 0.05). This means the residual fat signal is slightly lower with the Dixon compared to the SIPR technique (although not significant), while the SNR of blood is significantly higher with the Dixon technique. Vessel sharpness of the RCA was similar for Dixon and SPIR (57 ± 7 % vs. 56 ± 9 %, p = 0.2), while the RCA visualized vessel length was increased compared to SPIR fat suppression (107 ± 21 vs. 101 ± 21 mm, p < 0.001). For the LAD, vessel sharpness (50 ± 13 % vs. 50 ± 7 %, p = 0.4) and vessel length (92 ± 46 vs. 90 ± 47 mm, p = 0.4) were similar with both techniques. Consequently, the Dixon technique resulted in an improved visual score of the coronary arteries in the water fat separated images of healthy subjects (RCA: 4.6 ± 0.5 vs. 4.1 ± 0.7, p = 0.01, LAD: 4.1 ± 0.7 vs. 3.5 ± 0.8, p = 0.007). Conclusions: Dixon water-fat separation can significantly improve coronary artery image quality without the use of a contrast agent at 3T

Screening for proximal coronary artery anomalies with 3-dimensional MR coronary angiography

Under 35 years of age, 14% of sudden cardiac death in athletes is caused by a coronary artery anomaly (CAA). Free-breathing 3-dimensional magnetic resonance coronary angiography (3D-MRCA) has the potential to screen for CAA in athletes and non-athletes as an addition to a clinical cardiac MRI protocol. A 360 healthy men and women (207 athletes and 153 non-athletes) aged 18–60 years (mean age 31 ± 11 years, 37% women) underwent standard cardiac MRI with an additional 3D-MRCA within a maximum of 10 min scan time. The 3D-MRCA was screened for CAA. A 335 (93%) subjects had a technically satisfactory 3D-MRCA of which 4 (1%) showed a malignant variant of the right coronary artery (RCA) origin running between the aorta and the pulmonary trunk. Additional findings included three subjects with ventral rotation of the RCA with kinking and possible proximal stenosis, one person with additional stenosis and six persons with proximal myocardial bridging of the left anterior descending coronary artery. Coronary CT-angiography (CTA) was offered to persons with CAA (the CAA was confirmed in three, while one person declined CTA) and stenosis (the ventral rotation of the RCA was confirmed in two but without stenosis, while two people declined CTA). Overall 3D MRCA quality was better in athletes due to lower heart rates resulting in longer end-diastolic resting periods. This also enabled faster scan sequences. A 3D-MRCA can be used as part of the standard cardiac MRI protocol to screen young competitive athletes and non-athletes for anomalous proximal coronary arteries

Age-Related Differences in Ocular Features of a Naturalistic Free-Ranging Population of Rhesus Macaques

This is the final version. Available on open access from the Association for Research in Vision and Ophthalmology via the DOI in this recordPURPOSE: Rhesus macaques (Macaca mulatta) are the premier nonhuman primate model for studying human health and disease. We investigated if age was associated with clinically relevant ocular features in a large cohort of free-ranging rhesus macaques from Cayo Santiago, Puerto Rico. METHODS: We evaluated 120 rhesus macaques (73 males, 47 females) from 0 to 29 years old (mean ± SD: 12.6 ± 6.4) from September to December 2021. The ophthalmic evaluation included intraocular pressure (IOP) assessment, corneal pachymetry, biomicroscopy, A-scan biometry, automated refraction, and fundus photography after pupil dilation. The associations of age with the outcomes were investigated through multilevel mixed-effects models adjusted for sex and weight. RESULTS: On average, IOP, pachymetry, axial length, and automated refraction spherical equivalent were 18.37 ± 4.68 mmHg, 474.43 ± 32.21 µm, 19.49 ± 1.24 mm, and 0.30 ± 1.70 diopters (D), respectively. Age was significantly associated with pachymetry (β coefficient = -1.20; 95% confidence interval [CI], -2.27 to -0.14; P = 0.026), axial length (β coefficient = 0.03; 95% CI, 0.01 to 0.05; P = 0.002), and spherical equivalent (β coefficient = -0.12; 95% CI, -0.22 to -0.02; P = 0.015). No association was detected between age and IOP. The prevalence of cataracts in either eye was 10.83% (95% CI, 6.34-17.89) and was significantly associated with age (odds ratio [OR] = 1.20; 95% CI, 1.06-1.36; P = 0.004). Retinal drusen in either eye was observed in 15.00% (95% CI, 9.60-22.68) of animals, which was also significantly associated with age (OR = 1.14; 95% CI, 1.02-1.27; P = 0.020). CONCLUSIONS: Rhesus macaques exhibit age-related ocular associations similar to those observed in human aging, including decreased corneal thickness, increased axial length, myopic shift, and higher prevalence of cataract and retinal drusen.New Frontiers in Research FoundationNatural Sciences and Engineering Research CouncilCanada Research Chairs ProgramNational Aging InstituteBrightFocus FoundationNational Institutes of Health (NIH)University of Calgar

A study to assess changes in myocardial perfusion after treatment with spinal cord stimulation and percutaneous myocardial laser revascularisation; data from a randomised trial

<p>Abstract</p> <p>Background</p> <p>Spinal cord stimulation (SCS) and percutaneous myocardial laser revascularisation (PMR) are treatment modalities used to treat refractory angina pectoris, with the major aim of such treatment being the relief of disabling symptoms. This study compared the change in myocardial perfusion following SCS and PMR treatment.</p> <p>Methods</p> <p>Subjects with Canadian Cardiovascular Society class 3/4 angina and reversible perfusion defects as assessed by single-photon emission computed tomographic myocardial perfusion scintigraphy were randomised to SCS (34) or PMR (34). 28 subjects in each group underwent repeat myocardial perfusion imaging 12 months post intervention. Visual scoring of perfusion images was performed using a 20-segment model and a scale of 0 to 4.</p> <p>Results</p> <p>The mean (standard deviation) baseline summed rest score (SRS) and stress scores (SSS) were 4.6 (5.7) and 13.6 (9.0) in the PMR group and 6.1 (7.4) and 16.8 (11.6) in the SCS group. At 12 months, SRS was 5.5 (6.0) and SSS 15.3 (11.3) in the PMR group and 6.9 (8.2) and 15.1 (10.9) in the SCS group. There was no significant difference between the two treatment groups adjusted for baseline (p = 1.0 for SRS, p = 0.29 for SSS).</p> <p>Conclusion</p> <p>There was no significant difference in myocardial perfusion one year post treatment with SCS or PMR.</p

Vascular function assessed with cardiovascular magnetic resonance predicts survival in patients with advanced chronic kidney disease

<p>Abstract</p> <p>Background</p> <p>Increased arterial stiffness is associated with mortality in patients with chronic kidney disease. Cardiovascular magnetic resonance (CMR) permits assessment of the central arteries to measure aortic function.</p> <p>Methods</p> <p>We studied the relationship between central haemodynamics and outcome using CMR in 144 chronic kidney disease patients with estimated glomerular filtration rate <15 ml/min (110 on dialysis). Aortic distensibilty and volumetric arterial strain were calculated from cross sectional aortic volume and pulse pressure measured during the scan.</p> <p>Results</p> <p>Median follow up after the scan was 24 months. There were no significant differences in aortic distensibilty or aortic volumetric arterial strain between pre-dialysis and dialysis patients. Aortic distensibilty and volumetric arterial strain negatively correlated with age. Aortic distensibilty and volumetric arterial strain were lower in diabetics, patients with ischaemic heart disease and peripheral vascular disease. During follow up there were 20 deaths. Patients who died had lower aortic distensibilty than survivors. In a survival analysis, diabetes, systolic blood pressure and aortic distensibilty were independent predictors of mortality. There were 12 non-fatal cardiovascular events during follow up. Analysing the combined end point of death or a vascular event, diabetes, aortic distensibilty and volumetric arterial strain were predictors of events.</p> <p>Conclusion</p> <p>Deranged vascular function measured with CMR correlates with cardiovascular risk factors and predicts outcome. CMR measures of vascular function are potential targets for interventions to reduce cardiovascular risk.</p

Combined magnetic resonance coronary artery imaging, myocardial perfusion and late gadolinium enhancement in patients with suspected coronary artery disease

<p>Abstract</p> <p>Background</p> <p>Cardiovascular Magnetic Resonance (CMR) imaging offers methods for the detection of ischemia and myocardial infarction as well as visualization of the coronary arteries (MRCA). However, a direct comparison of adenosine perfusion (PERF), late gadolinium enhancement (LGE) and MRCA or the results of their combination has not been performed. Aim of the study was to evaluate the feasibility/diagnostic performance of rest/stress perfusion, late gadolinium enhancement and MRCA and their combination in patients with suspected coronary artery disease (CAD) in comparison to invasive angiography.</p> <p>Methods</p> <p>Fifty-four patients (60 ± 10 years, 35 men, CAD 48%) underwent CMR including MRCA (steady state free precession, navigator whole heart approach, spatial resolution 0.7 × 0.7 × .0.9 mm, trigger delay and temporal resolution adjusted individually), stress PERF (adenosine 140 μg/min/kg), rest PERF (SSFP, 3 short axis, 1 saturation prepulse per slice) and LGE (3D inversion recovery technique) using Gd-BOPTA. Images were analyzed visually. Stenosis >50% in invasive angiography was considered significant.</p> <p>Results</p> <p>Mean study time was 68 ± 11 minutes. Sensitivity for PERF, LGE, MRCA and the combination of PERF/LGE and PERF/LGE/MRCA was 87%, 50%, 91%, 88% and 92%, respectively and specificity 88%, 96%, 46%, 88% and 56%, respectively. If image quality of MRCA was excellent (n = 18) the combination of MRCA/PERF/LGE yield a sensitivity of 86% and specificity of 91%. However, no test or combination improved diagnostic performance significantly compared to PERF alone.</p> <p>Conclusion</p> <p>In patients with CAD, the combination of stress PERF, LGE and MRCA is feasible. When compared to invasive angiography, adenosine stress perfusion outperforms CMR coronary angiography in direct comparison and yields the best results with non-significant improvement in combination with LGE and significant deterioration in combination with MRCA. MRCA may be of additional value only in a minority of patients with excellent image quality.</p

Predicting clinically unrecognized coronary artery disease: use of two- dimensional echocardiography

<p>Abstract</p> <p>Background</p> <p>2-D Echo is often performed in patients without history of coronary artery disease (CAD). We sought to determine echo features predictive of CAD.</p> <p>Methods</p> <p>2-D Echo of 328 patients without known CAD performed within one year prior to stress myocardial SPECT and angiography were reviewed. Echo features examined were left ventricular and atrial enlargement, LV hypertrophy, wall motion abnormality (WMA), LV ejection fraction (EF) < 50%, mitral annular calcification (MAC) and aortic sclerosis/stenosis (AS). High risk myocardial perfusion abnormality (MPA) was defined as >15% LV perfusion defect or multivessel distribution. Severe coronary artery stenosis (CAS) was defined as left main, 3 VD or 2VD involving proximal LAD.</p> <p>Results</p> <p>The mean age was 62 ± 13 years, 59% men, 29% diabetic (DM) and 148 (45%) had > 2 risk factors. Pharmacologic stress was performed in 109 patients (33%). MPA was present in 200 pts (60%) of which, 137 were high risk. CAS was present in 166 pts (51%), 75 were severe. Of 87 patients with WMA, 83% had MPA and 78% had CAS. Multivariate analysis identified age >65, male, inability to exercise, DM, WMA, MAC and AS as independent predictors of MPA and CAS. Independent predictors of high risk MPA and severe CAS were age, DM, inability to exercise and WMA.</p> <p>2-D echo findings offered incremental value over clinical information in predicting CAD by angiography. (Chi square: 360 vs. 320 p = 0.02).</p> <p>Conclusion</p> <p>2-D Echo was valuable in predicting presence of physiological and anatomical CAD in addition to clinical information.</p

A Novel High-Content Flow Cytometric Method for Assessing the Viability and Damage of Rat Retinal Ganglion Cells

PURPOSE: The aim of the study was to develop a high-content flow cytometric method for assessing the viability and damage of small, medium, and large retinal ganglion cells (RGCs) in N-methyl-D-aspartic acid (NMDA)-injury model. METHODS/RESULTS: Retinal toxicity was induced in rats by intravitreal injection of NMDA and RGCs were retrogradely labeled with Fluoro-Gold (FG). Seven days post-NMDA injection, flatmount and flow cytometric methods were used to evaluate RGCs. In addition, the RGC area diameter (D((a))) obtained from retinal flatmount imaging were plotted versus apparent volume diameter (D((v))) obtained from flow cytometry for the same cumulative cell number (sequentially from small to large RGCs) percentile (Q) to establish their relationship for accurately determining RGC sizes. Good correlation (r = 0.9718) was found between D((a)) and apparent D((v)). Both flatmount and flow cytometric analyses of RGCs showed that 40 mM NMDA significantly reduced the numbers of small and medium RGCs but not large RGCs. Additionally, flow cytometry showed that the geometric means of FG and thy-1 intensities in three types of RGCs decreased to 90.96±2.24% (P<0.05) and 91.78±1.89% (P>0.05) for small, 69.62±2.11% (P<0.01) and 69.07±2.98% (P<0.01) for medium, and 69.68±6.48% (P<0.05) and 69.91±6.23% (P<0.05) for large as compared with the normal RGCs. CONCLUSION: The established flow cytometric method provides high-content analysis for differential evaluation of RGC number and status and should be useful for the evaluation of various models of optic nerve injury and the effects of potential neuroprotective agents

CXCR3 Antagonism of SDF-1(5-67) Restores Trabecular Function and Prevents Retinal Neurodegeneration in a Rat Model of Ocular Hypertension

Glaucoma, the most common cause of irreversible blindness, is a neuropathy commonly initiated by pathological ocular hypertension due to unknown mechanisms of trabecular meshwork degeneration. Current antiglaucoma therapy does not target the causal trabecular pathology, which may explain why treatment failure is often observed. Here we show that the chemokine CXCL12, its truncated form SDF-1(5-67), and the receptors CXCR4 and CXCR3 are expressed in human glaucomatous trabecular tissue and a human trabecular cell line. SDF-1(5-67) is produced under the control of matrix metallo-proteinases, TNF-α, and TGF-β2, factors known to be involved in glaucoma. CXCL12 protects in vitro trabecular cells from apoptotic death via CXCR4 whereas SDF-1(5-67) induces apoptosis through CXCR3 and caspase activation. Ocular administration of SDF-1(5-67) in the rat increases intraocular pressure. In contrast, administration of a selective CXCR3 antagonist in a rat model of ocular hypertension decreases intraocular pressure, prevents retinal neurodegeneration, and preserves visual function. The protective effect of CXCR3 antagonism is related to restoration of the trabecular function. These data demonstrate that proteolytic cleavage of CXCL12 is involved in trabecular pathophysiology, and that local administration of a selective CXCR3 antagonist may be a beneficial therapeutic strategy for treating ocular hypertension and subsequent retinal degeneration