The therapeutic potential of mesenchymal stem cells (MSCs) for restoring cardiac function after cardiomyocyte loss remains controversial. Engineered cardiac tissues (ECTs) offer a simplified three-dimensional in vitro model system to evaluate stem cell therapies. We hypothesized that contractile properties of dysfunctional ECTs would be enhanced by MSC treatment. ECTs were created from neonatal rat cardiomyocytes with and without bone marrow-derived adult rat MSCs in a type-I collagen and Matrigel scaffold using custom elastomer molds with integrated cantilever force sensors. Three experimental groups included the following: (1) baseline condition ECT consisting only of myocytes, (2) 50% myocyte-depleted ECT, modeling a dysfunctional state, and (3) 50% myocyte-depleted ECT plus 10% MSC, modeling dysfunctional myocardium with intervention. Developed stress (DS) and pacing threshold voltage (VT) were measured using 2-Hz field stimulation at 37°C on culture days 5, 10, 15, and 20. By day 5, DS of myocyte-depleted ECTs was significantly lower than baseline, and VT was elevated. In MSC-supplemented ECTs, DS and VT were significantly better than myocyte-depleted values, approaching baseline ECTs. Findings were similar through culture day 15, but lost significance at day 20. Trends in DS were partly explained by changes in the cell number and alignment with time. Thus, supplementing myocyte-depleted ECTs with MSCs transiently improved contractile function and compensated for a 50% loss of cardiomyocytes, mimicking recent animal studies and clinical trials and supporting the potential of MSCs for myocardial therapy.

Pulsatile Tinnitus (PT) is a pulse-synchronous sound heard in the absence of an external source. PT is often related to abnormal flow in vascular structures near the cochlea. One vascular territory implicated in PT is the internal jugular vein (IJV). Using computational fluid dynamics (CFD) based on patient-specific Magnetic Resonance Imaging (MRI), we investigated the flow within the IJV of seven subjects, four symptomatic and three asymptomatic of PT. We found that there were two extreme anatomic types classified by the shape and position of the jugular bulbs: elevated and rounded. PT patients had elevated jugular bulbs that led to a distinctive helical flow pattern within the proximal internal jugular vein. Asymptomatic subjects generally had rounded jugular bulbs that neatly redirected flow from the sigmoid sinus directly into the jugular vein. These two flow patterns were quantified by calculating the length-averaged streamline curvature of the flow within the proximal jugular vein: 130.3 ± 8.1 m-1 for geometries with rounded bulbs, 260.7 ± 29.4 m-1 for those with elevated bulbs (P < 0.005). Our results suggest that variations in the jugular bulb geometry lead to distinct flow patterns that are linked to PT, but further investigation is needed to determine if the vortex pattern is causal to sound generation.

Background and Purpose Case reports demonstrate coiling of sigmoid sinus diverticulum (SSD) can treat pulsatile tinnitus (PT). We hypothesize MR 4D Flow (4DF) and computational fluid dynamics (CFD) will reveal distinct blood flow patterns in the venous outflow tract in these patients. Materials and Methods Patients with PT of suspected venous etiology underwent MRI at 3T, using venous phase contrast-enhanced MR angiography (CE-MRA), 4DF, and 2D phase contrast. The CE-MRA contours were evaluated to determine the presence and extent of SSD. CFD analysis was performed using the 4DF inlet flow and the lumenal contours from CE-MRA as boundary conditions. In addition, CFD was also performed for the expected post-treatment conditions by smoothing the venous geometry to exclude the SSD from the anatomic boundary conditions. Streamlines were generated from the 4DF and CFD velocity maps and flow patterns were examined for the presence of rotational components. Results Twenty-five patients with PT of suspected venous etiology and 10 control subjects were enrolled. Five (20%) of the symptomatic subjects had SSD, all associated with an upstream stenosis. In each of these cases, but none of the controls, a stenosis-related flow-jet was directed toward the opening of the SSD with rotational flow patterns in the SSD and parent sigmoid sinus on both 4DF and CFD that were absent in controls. Conclusion Consistent patterns of blood flow can be visualized in SSD and the parent sinus using 4DF and CFD. Strong components of rotational blood flow were seen in subjects with SSD that were absent in controls.

Segmentation of the geometric morphology of abdominal aortic aneurysm is important for interventional planning. However, the segmentation of both the lumen and the outer wall of aneurysm in magnetic resonance (MR) image remains challenging. This study proposes a registration based segmentation methodology for efficiently segmenting MR images of abdominal aortic aneurysms. The proposed methodology first registers the contrast enhanced MR angiography (CE-MRA) and black-blood MR images, and then uses the Hough transform and geometric active contours to extract the vessel lumen by delineating the inner vessel wall directly from the CE-MRA. The proposed registration based geometric active contour is applied to black-blood MR images to generate the outer wall contour. The inner and outer vessel wall are then fused presenting the complete vessel lumen and wall segmentation. The results obtained from 19 cases showed that the proposed registration based geometric active contour model was efficient and comparable to manual segmentation and provided a high segmentation accuracy with an average Dice value reaching 89.79%.

Background and Purpose Idiopathic intracranial hypertension (IIH) is commonly associated with transverse sinus stenosis - a venous cause of pulsatile tinnitus (PT). In IIH patients, CSF drainage via lumbar puncture (LP) decreases intracranial pressure, which relieves the stenosis, and may provide at least temporary cessation of PT. The objective of this study is to evaluate changes in venous blood flow caused by lowered intracranial pressure in PT patients to help identify the cause of PT. Materials and methods 10 patients with suspected transverse sinus stenosis as a venous etiology for PT symptoms underwent MRI before and after LP in the same session. The protocol included flow assessment and rating of PT intensity before and after LP, and MRV before LP. Post-LP MRV was performed in one subject. Results There was an LP induced reduction in venous peak velocity that correlated with the opening pressure (r=−0.72, p=0.019) without a concomitant reduction in flow rate. Patients with flow jets had their peak velocity reduced by 0.30±0.18m/s (p=0.002), correlating with reduction in CSF pressure (r=0.82, p=0.024) and the reduction in subjectively scored PT intensity (r=0.78, p=0.023). The post-LP MRV demonstrated alleviation of the stenosis. Conclusion Our results show a LP induced reduction in venous peak velocity without a concomitant reduction in flow rate. We hypothesize the reduction is caused by the expansion of the stenosis after LP. Our results further show a correlation between the peak velocity and PT intensity, suggesting the flow jet to be instrumental in the development of sound.