Laser brain cancer surgery in a xenograft model guided by optical coherence tomography.

Higher precision surgical devices are needed for tumor resections near critical brain structures. The goal of this study is to demonstrate feasibility of a system capable of precise and bloodless tumor ablation. An image-guided laser surgical system is presented for excision of brain tumors in vivo in a murine xenograft model. The system combines optical coherence tomography (OCT) guidance with surgical lasers for high-precision tumor ablation (Er:YAG) and microcirculation coagulation (Thulium (Tm) fiber laser). Methods: A fluorescent human glioblastoma cell line was injected into mice and allowed to grow four weeks. Craniotomies were performed and tumors were imaged with confocal fluorescence microscopy. The mice were subsequently OCT imaged prior, during and after laser coagulation and/or ablation. The prior OCT images were used to compute three-dimensional tumor margin and angiography images, which guided the coagulation and ablation steps. Histology of the treated regions was then compared to post-treatment OCT images. Results: Tumor sizing based on OCT margin detection matched histology to within experimental error. Although fluorescence microscopy imaging showed the tumors were collocated with OCT imaging, margin assessment using confocal microscopy failed to see the extent of the tumor beyond ~ 250 µm in depth, as verified by OCT and histology. The two-laser approach to surgery utilizing Tm wavelength for coagulation and Er:YAG for ablation yielded bloodless resection of tumor regions with minimal residual damage as seen in histology. Conclusion: Precise and bloodless tumor resection under OCT image guidance is demonstrated in the murine xenograft brain cancer model. Tumor margins and vasculature are accurately made visible without need for exogenous contrast agents.

Trabecular cutting: a novel surgical therapy to increase diastolic compliance.

Heart failure with preserved ejection fraction (HFpEF) is a common cause of hospital admission in patients over 65 yr old and has high mortality. HFpEF is characterized by left ventricular (LV) hypertrophy that reduces compliance. Current HFpEF therapies control symptoms, but no existing medications or therapies can sustainably increase LV compliance. LV trabeculae develop hypertrophy and fibrosis that contribute to reduced LV compliance. This study expands our previous results in ex vivo human hearts to show that severing LV trabeculae increases diastolic compliance in an ex vivo working rabbit heart model. Trabecular cutting was performed in ex vivo rabbit hearts set up in a working heart perfusion system perfused with oxygenated Krebs-Henseleit buffer. A hook was inserted in the LV to cut trabeculae. End-systolic and end-diastolic pressure-volume relationships during transient preload reduction were recorded using an admittance catheter in the following three groups: control (no cutting; n = 9), mild cutting (15 cuts; n = 5), and aggressive cutting (30 cuts; n = 5). In a second experiment, each heart served as its own control. Hemodynamic data were recorded before and after trabecular cutting (n = 10) or sham cutting (n = 5) within the same heart. In the first experiments, trabecular cutting did not affect systolic function (P > 0.05) but significantly increased overall diastolic compliance (P = 0.009). Greater compliance was seen as trabecular cutting increased (P = 0.002, r2 = 0.435). In the second experiment, significant increases in systolic function (P = 0.048) and diastolic compliance (P = 0.002) were seen after trabecular cutting compared with baseline. In conclusion, trabecular cutting significantly increases diastolic compliance without reducing systolic function.NEW & NOTEWORTHY We postulate that, in mammalian hearts, free-running trabeculae carneae exist to provide tensile support to the left ventricle and minimize diastolic wall stress. Because of hypertrophy and fibrosis of trabeculae in patients with left ventricular hypertrophy, this supportive role can become pathologic, worsening diastolic compliance. We demonstrate a novel operation involving cutting trabeculae as a method to acutely increase diastolic compliance in patients presenting with heart failure and diastolic dysfunction to improve their left ventricle compliance.

Comparison of Biomechanical Properties and Microstructure of Trabeculae Carneae, Papillary Muscles, and Myocardium in the Human Heart.

Trabeculae carneae account for a significant portion of human ventricular mass, despite being considered embryologic remnants. Recent studies have found trabeculae hypertrophy and fibrosis in hypertrophied left ventricles with various pathological conditions. The objective of this study was to investigate the passive mechanical properties and microstructural characteristics of trabeculae carneae and papillary muscles compared to the myocardium in human hearts. Uniaxial tensile tests were performed on samples of trabeculae carneae and myocardium strips, while biaxial tensile tests were performed on samples of papillary muscles and myocardium sheets. The experimental data were fitted with a Fung-type strain energy function and material coefficients were determined. The secant moduli at given diastolic stress and strain levels were determined and compared among the tissues. Following the mechanical testing, histology examinations were performed to investigate the microstructural characteristics of the tissues. Our results demonstrated that the trabeculae carneae were significantly stiffer (Secant modulus SM2 = 80.06 ± 10.04 KPa) and had higher collagen content (16.10 ± 3.80%) than the myocardium (SM2 = 55.14 ± 20.49 KPa, collagen content = 10.06 ± 4.15%) in the left ventricle. The results of this study improve our understanding of the contribution of trabeculae carneae to left ventricular compliance and will be useful for building accurate computational models of the human heart.

Tunable Buckled Beams with Mesoporous PVDF-TrFE/SWCNT Composite Film for Energy Harvesting.

By incorporating mesoporous piezoelectric materials and tuning mechanical boundary conditions a simple beam structure can significantly take advantage of limited mechanical displacements for energy harvesting. Specifically, we employed a mesoporous PVDF-TrFE composite thin film mixed with single-wall carbon nanotubes to improve the formation of the crystalline phase in this piezoelectric polymer. The film was then patterned on a thin buckled beam to form a compact energy harvester, which was used to study the effects of two boundary conditions, including the end rotation angle and the location of a mechanical stop along the beam. We carefully designed controlled experiments using mesoporous PVDF-TrFE film and PVDF-TrFE/SWCNT composite films, both of which were tested under two cases of boundary conditions, namely, the rotation of the end angle and the addition of a mechanical stop. The voltage and current of the energy harvester under these two boundary conditions were, respectively, increased by approximately 160.1% and 200.5% compared to the results of its counterpart without imposing any boundary conditions. Thereby, our study offers a promising platform for efficiently powering implantable and wearable devices for harnessing energy from the human body which would otherwise have been wasted.

Impact of ticagrelor and aspirin versus clopidogrel and aspirin in symptomatic patients with peripheral arterial disease: Thrombus burden assessed by optical coherence tomography.

PURPOSE: To compare OCT identified white thrombus decline, neointimal hyperplasia and clinical outcomes of patients treated with ticagrelor plus aspirin with those patients treated with clopidogrel plus aspirin after peripheral interventions. BACKGROUND: Ticagrelor is a potent platelet inhibitor. In patients with coronary artery disease, ticagrelor and aspirin demonstrated reduced rates of stent thrombosis, compared to aspirin and clopidogrel. The clinical importance of potent antiplatelet inhibition after peripheral endovascular interventions is unknown. METHODS: We enrolled 18 patients with superficial femoral artery disease and the presence of OCT-detected clot post-stent placement. Patients were randomized to 75 mg clopidogrel once daily for 1 month vs. 90 mg ticagrelor twice daily for 6 months, both in addition to 81 mg aspirin for 6 months. Clot volumes, ankle-brachial index (ABI), 6-minute walk test, and Rutherford classification were measured at baseline and 6-month follow-up. Neointimal hyperplasia and neovascularization were calculated at 6-month follow-up. RESULTS: N = 11 patients were enrolled in the clopidogrel group and N = 7 in the ticagrelor group. There was a significantly greater decrease in white thrombus in the ticagrelor group (median volume/stent length (0.067 vs 0.014 mm3/mm, p = 0.05)). No differences were found in % neointima (0.412 vs 0.536 mm3/mm, p = 0.44) and neovascularization (28 vs 44, p = 0.16). ABI and Rutherford classification were improved significantly after 6 months in the clopidogrel group, with no difference between groups at 6 months in ABI or Rutherford. CONCLUSION: In symptomatic patients with PAD, ticagrelor showed significant improvement relative to clopidogrel with respect to white thrombus burden decline.