Capturing the Cardiac Injury Response of Targeted Cell Populations via Cleared Heart Three-Dimensional Imaging.
- 作者列表："Salamon RJ","Zhang Z","Mahmoud AI
:Cardiovascular disease outranks all other causes of death and is responsible for a staggering 31% of mortalities worldwide. This disease manifests in cardiac injury, primarily in the form of an acute myocardial infarction. With little resilience following injury, the once healthy cardiac tissue will be replaced by fibrous, non-contractile scar tissue and often be a prelude to heart failure. To identify novel treatment options in regenerative medicine, research has focused on vertebrates with innate regenerative capabilities. One such model organism is the neonatal mouse, which responds to cardiac injury with robust myocardial regeneration. In order to induce an injury in the neonatal mouse that is clinically relevant, we have developed a surgery to occlude the left anterior descending artery (LAD), mirroring a myocardial infarction triggered by atherosclerosis in the human heart. When matched with the technology to track changes both within cardiomyocytes and non-myocyte populations, this model provides us with a platform to identify the mechanisms that guide heart regeneration. Gaining insight into changes in cardiac cell populations following injury once relied heavily on methods such as tissue sectioning and histological examination, which are limited to two-dimensional analysis and often damage the tissue in the process. Moreover, these methods lack the ability to trace changes in cell lineages, instead providing merely a snapshot of the injury response. Here, we describe how technologically advanced methods in lineage tracing models, whole organ clearing, and three-dimensional (3D) whole-mount microscopy can be used to elucidate mechanisms of cardiac repair. With our protocol for neonatal mouse myocardial infarction surgery, tissue clearing, and 3D whole organ imaging, the complex pathways that induce cardiomyocyte proliferation can be unraveled, revealing novel therapeutic targets for cardiac regeneration.
: 心血管疾病超过所有其他死亡原因，导致全球惊人的31% 的死亡率。这种疾病表现为心脏损伤，主要表现为急性心肌梗塞。在损伤后几乎没有恢复力的情况下，曾经健康的心脏组织将被纤维性、非收缩性瘢痕组织取代，并且常常是心力衰竭的前奏。为了确定再生医学中的新治疗方案，研究集中在具有先天再生能力的脊椎动物上。一种这样的模型生物是新生小鼠，其以稳健的心肌再生响应心脏损伤。为了在新生小鼠中诱导临床相关的损伤，我们开发了一种手术来闭塞左前降支动脉 (LAD)，反映由人心脏中的动脉粥样硬化引发的心肌梗塞。当与跟踪心肌细胞和非心肌细胞群体变化的技术相匹配时，该模型为我们提供了一个平台来确定引导心脏再生的机制。了解损伤后心脏细胞群的变化曾经严重依赖于组织切片和组织学检查等方法，这些方法仅限于二维分析，并且经常在该过程中损伤组织。此外，这些方法缺乏追踪细胞谱系变化的能力，而是仅提供损伤反应的快照。在这里，我们描述了如何使用谱系追踪模型、全器官清除和三维 (3D) 全显微镜技术先进的方法来阐明心脏修复的机制。通过我们的新生小鼠心肌梗死手术、组织清除和3D全器官成像方案，可以解开诱导心肌细胞增殖的复杂通路，揭示心脏再生的新治疗靶点。
METHODS:OBJECTIVES:The aim was to evaluate the image quality and sensitivity to artifacts of compressed sensing (CS) acceleration technique, applied to 3D or breath-hold sequences in different clinical applications from brain to knee. METHODS:CS with an acceleration from 30 to 60% and conventional MRI sequences were performed in 10 different applications in 107 patients, leading to 120 comparisons. Readers were blinded to the technique for quantitative (contrast-to-noise ratio or functional measurements for cardiac cine) and qualitative (image quality, artifacts, diagnostic findings, and preference) image analyses. RESULTS:No statistically significant difference in image quality or artifacts was found for each sequence except for the cardiac cine CS for one of both readers and for the wrist 3D proton density (PD)-weighted CS sequence which showed less motion artifacts due to the reduced acquisition time. The contrast-to-noise ratio was lower for the elbow CS sequence but not statistically different in all other applications. Diagnostic findings were similar between conventional and CS sequence for all the comparisons except for four cases where motion artifacts corrupted either the conventional or the CS sequence. CONCLUSIONS:The evaluated CS sequences are ready to be used in clinical daily practice except for the elbow application which requires a lower acceleration. The CS factor should be tuned for each organ and sequence to obtain good image quality. It leads to 30% to 60% acceleration in the applications evaluated in this study which has a significant impact on clinical workflow. KEY POINTS:• Clinical implementation of compressed sensing (CS) reduced scan times of at least 30% with only minor penalty in image quality and no change in diagnostic findings. • The CS acceleration factor has to be tuned separately for each organ and sequence to guarantee similar image quality than conventional acquisition. • At least 30% and up to 60% acceleration is feasible in specific sequences in clinical routine.
METHODS:BACKGROUND:The main surgical techniques for spontaneous basal ganglia hemorrhage include stereotactic aspiration, endoscopic aspiration, and craniotomy. However, credible evidence is still needed to validate the effect of these techniques. OBJECTIVE:To explore the long-term outcomes of the three surgical techniques in the treatment of spontaneous basal ganglia hemorrhage. METHODS:Five hundred and sixteen patients with spontaneous basal ganglia hemorrhage who received stereotactic aspiration, endoscopic aspiration, or craniotomy were reviewed retrospectively. Six-month mortality and the modified Rankin Scale score were the primary and secondary outcomes, respectively. A multivariate logistic regression model was used to assess the effects of different surgical techniques on patient outcomes. RESULTS:For the entire cohort, the 6-month mortality in the endoscopic aspiration group was significantly lower than that in the stereotactic aspiration group (odds ratio (OR) 4.280, 95% CI 2.186 to 8.380); the 6-month mortality in the endoscopic aspiration group was lower than that in the craniotomy group, but the difference was not significant (OR=1.930, 95% CI 0.835 to 4.465). A further subgroup analysis was stratified by hematoma volume. The mortality in the endoscopic aspiration group was significantly lower than in the stereotactic aspiration group in the medium (≥40-<80 mL) (OR=2.438, 95% CI 1.101 to 5.402) and large hematoma subgroup (≥80 mL) (OR=66.532, 95% CI 6.345 to 697.675). Compared with the endoscopic aspiration group, a trend towards increased mortality was observed in the large hematoma subgroup of the craniotomy group (OR=8.721, 95% CI 0.933 to 81.551). CONCLUSION:Endoscopic aspiration can decrease the 6-month mortality of spontaneous basal ganglia hemorrhage, especially in patients with a hematoma volume ≥40 mL.
METHODS:OBJECTIVE:The primary purpose of this study was to evaluate the effectiveness of a three-dimensional (3D) software tool (smart planes) for displaying fetal brain planes, and the secondary purpose was to evaluate its accuracy in performing automatic measurements. MATERIAL AND METHODS:This prospective study included singleton fetuses with a gestational age (GA) greater than 18 weeks. Transabdominal two-dimensional ultrasound (2DUS) and 3D smart planes images were respectively used to obtain the basic planes of the fetal brain, with five parameters measured. The images, by either two-dimensional (2D) manual or 3D automatic operation, were reviewed by two experienced sonographers. The agreements between two measurements were analyzed. RESULTS:A total of 226 cases were included. The rates of successful detection by automatic display were as high as 80%. There was substantial agreement between the measurements of the biparietal diameter, head circumference and transcerebellar diameter, but poor agreement between the measurements of cisterna magna and lateral ventricle width. CONCLUSIONS:Smart Planes might be valuable for the rapid evaluation of fetal brain, because it simplifies the evaluation process. However, the technology requires improvement. In addition, this technology cannot replace the conventional manual US scans; it can only be used as an additional approach.