BME frontiers最新文献

Objective and Impact Statement. Identifying benign mimics of prostatic adenocarcinoma remains a significant diagnostic challenge. In this work, we developed an approach based on label-free, high-resolution molecular imaging with multispectral deep ultraviolet (UV) microscopy which identifies important prostate tissue components, including basal cells. This work has significant implications towards improving the pathologic assessment and diagnosis of prostate cancer. Introduction. One of the most important indicators of prostate cancer is the absence of basal cells in glands and ducts. However, identifying basal cells using hematoxylin and eosin (H&E) stains, which is the standard of care, can be difficult in a subset of cases. In such situations, pathologists often resort to immunohistochemical (IHC) stains for a definitive diagnosis. However, IHC is expensive and time-consuming and requires more tissue sections which may not be available. In addition, IHC is subject to false-negative or false-positive stains which can potentially lead to an incorrect diagnosis. Methods. We leverage the rich molecular information of label-free multispectral deep UV microscopy to uniquely identify basal cells, luminal cells, and inflammatory cells. The method applies an unsupervised geometrical representation of principal component analysis to separate the various components of prostate tissue leading to multiple image representations of the molecular information. Results. Our results show that this method accurately and efficiently identifies benign and malignant glands with high fidelity, free of any staining procedures, based on the presence or absence of basal cells. We further use the molecular information to directly generate a high-resolution virtual IHC stain that clearly identifies basal cells, even in cases where IHC stains fail. Conclusion. Our simple, low-cost, and label-free deep UV method has the potential to improve and facilitate prostate cancer diagnosis by enabling robust identification of basal cells and other important prostate tissue components.

Objective and Impact Statement. We use deep learning models to classify cervix images-collected with a low-cost, portable Pocket colposcope-with biopsy-confirmed high-grade precancer and cancer. We boost classification performance on a screened-positive population by using a class-balanced loss and incorporating green-light colposcopy image pairs, which come at no additional cost to the provider. Introduction. Because the majority of the 300,000 annual deaths due to cervical cancer occur in countries with low- or middle-Human Development Indices, an automated classification algorithm could overcome limitations caused by the low prevalence of trained professionals and diagnostic variability in provider visual interpretations. Methods. Our dataset consists of cervical images ($n=\mathrm{1,760}$) from 880 patient visits. After optimizing the network architecture and incorporating a weighted loss function, we explore two methods of incorporating green light image pairs into the network to boost the classification performance and sensitivity of our model on a test set. Results. We achieve an area under the receiver-operator characteristic curve, sensitivity, and specificity of 0.87, 75%, and 88%, respectively. The addition of the class-balanced loss and green light cervical contrast to a Resnet-18 backbone results in a 2.5 times improvement in sensitivity. Conclusion. Our methodology, which has already been tested on a prescreened population, can boost classification performance and, in the future, be coupled with Pap smear or HPV triaging, thereby broadening access to early detection of precursor lesions before they advance to cancer.

Objective. Laser-treated surfaces for ventricular assist devices. Impact Statement. This work has scientific impact since it proposes a biofunctional surface created with laser processing in bioinert titanium. Introduction. Cardiovascular diseases are the world's leading cause of death. An especially debilitating heart disease is congestive heart failure. Among the possible therapies, heart transplantation and mechanical circulatory assistance are the main treatments for its severe form at a more advanced stage. The development of biomaterials for ventricular assist devices is still being carried out. Although polished titanium is currently employed in several devices, its performance could be improved by enhancing the bioactivity of its surface. Methods. Aiming to improve the titanium without using coatings that can be detached, this work presents the formation of laser-induced periodic surface structures with a topology suitable for cell adhesion and neointimal tissue formation. The surface was modified by femtosecond laser ablation and cell adhesion was evaluated in vitro by using fibroblast cells. Results. The results indicate the formation of the desired topology, since the cells showed the appropriate adhesion compared to the control group. Scanning electron microscopy showed several positive characteristics in the cells shape and their surface distribution. The in vitro results obtained with different topologies point that the proposed LIPSS would provide enhanced cell adhesion and proliferation. Conclusion. The laser processes studied can create new interactions in biomaterials already known and improve the performance of biomaterials for use in ventricular assist devices.

Objective. This paper is an initial work towards developing particle-mediated histotripsy (PMH) as a novel method of treating catheter-based medical device (CBMD) intraluminal biofilms. Impact Statement. CBMDs commonly become infected with bacterial biofilms leading to medical device failure, infection, and adverse patient outcomes. Introduction. Histotripsy is a noninvasive focused ultrasound ablation method that was recently proposed as a novel method to remove intraluminal biofilms. Here, we explore the potential of combining histotripsy with acoustically active particles to develop a PMH approach that can noninvasively remove biofilms without the need for high acoustic pressures or real-time image guidance for targeting. Methods. Histotripsy cavitation thresholds in catheters containing either gas-filled microbubbles (MBs) or fluid-filled nanocones (NCs) were determined. The ability of these particles to sustain cavitation over multiple ultrasound pulses was tested after a series of histotripsy exposures. Next, the ability of PMH to generate selective intraluminal cavitation without generating extraluminal cavitation was tested. Finally, the biofilm ablation and bactericidal capabilities of PMH were tested using both MBs and NCs. Results. PMH significantly reduced the histotripsy cavitation threshold, allowing for selective luminal cavitation for both MBs and NCs. Results further showed PMH successfully removed intraluminal biofilms in Tygon catheters. Finally, results from bactericidal experiments showed minimal reduction in bacteria viability. Conclusion. The results of this study demonstrate the potential for PMH to provide a new modality for removing bacterial biofilms from CBMDs and suggest that additional work is warranted to develop histotripsy and PMH for treatment of CBMD intraluminal biofilms.

Objective and Impact Statement. This study examined the efficacy and safety of pulsed, low-intensity focused ultrasound (LIFU) and determined its ability to provide neuroprotection in a murine permanent middle cerebral artery occlusion (pMCAO) model. Introduction. Focused ultrasound (FUS) has emerged as a new therapeutic strategy for the treatment of ischemic stroke; however, its nonthrombolytic properties remain ill-defined. Therefore, we examined how LIFU influenced neuroprotection and vascular changes following stroke. Due to the critical role of leptomeningeal anastomoses or pial collateral vessels, in cerebral blood flow restoration and tissue protection following ischemic stroke, we also investigated their growth and remodeling. Methods. Mice were exposed to transcranial LIFU (fundamental frequency: 1.1 MHz, sonication duration: 300 ms, interstimulus interval: 3 s, pulse repetition frequency: 1 kHz, duty cycle per pulse: 50%, and peak negative pressure: -2.0 MPa) for 30 minutes following induction of pMCAO and then evaluated for infarct volume, blood-brain barrier (BBB) disruption, and pial collateral remodeling at 24 hrs post-pMCAO. Results. We found significant neuroprotection in mice exposed to LIFU compared to mock treatment. These findings correlated with a reduced area of IgG deposition in the cerebral cortex, suggesting attenuation of BBB breakdown under LIFU conditions. We also observed increased diameter of CD31-postive microvessels in the ischemic cortex. We observed no significant difference in pial collateral vessel size between FUS and mock treatment at 24 hrs post-pMCAO. Conclusion. Our data suggests that therapeutic use of LIFU may induce protection through microvascular remodeling that is not related to its thrombolytic activity.

Objective. To develop a 3D shear wave elastography (SWE) technique using a 2D row column addressing (RCA) array, with either external vibration or acoustic radiation force (ARF) as the shear wave source. Impact Statement. The proposed method paves the way for clinical translation of 3D SWE based on the 2D RCA, providing a low-cost and high volume rate solution that is compatible with existing clinical systems. Introduction. SWE is an established ultrasound imaging modality that provides a direct and quantitative assessment of tissue stiffness, which is significant for a wide range of clinical applications including cancer and liver fibrosis. SWE requires high frame rate imaging for robust shear wave tracking. Due to the technical challenges associated with high volume rate imaging in 3D, current SWE techniques are typically confined to 2D. Advancing SWE from 2D to 3D is significant because of the heterogeneous nature of tissue, which demands 3D imaging for accurate and comprehensive evaluation. Methods. A 3D SWE method using a RCA array was developed with a volume rate up to 2000 Hz. The performance of the proposed method was systematically evaluated on tissue-mimicking elasticity phantoms and in an in vivo case study. Results. 3D shear wave motion induced by either external vibration or ARF was successfully detected with the proposed method. Robust 3D shear wave speed maps were reconstructed for phantoms and in vivo. Conclusion. The high volume rate 3D imaging provided by the 2D RCA array provides a robust and practical solution for 3D SWE with a clear pathway for future clinical translation.

Objective and Impact Statement. We present a fully automated hematological analysis framework based on single-channel (single-wavelength), label-free deep-ultraviolet (UV) microscopy that serves as a fast, cost-effective alternative to conventional hematology analyzers. Introduction. Hematological analysis is essential for the diagnosis and monitoring of several diseases but requires complex systems operated by trained personnel, costly chemical reagents, and lengthy protocols. Label-free techniques eliminate the need for staining or additional preprocessing and can lead to faster analysis and a simpler workflow. In this work, we leverage the unique capabilities of deep-UV microscopy as a label-free, molecular imaging technique to develop a deep learning-based pipeline that enables virtual staining, segmentation, classification, and counting of white blood cells (WBCs) in single-channel images of peripheral blood smears. Methods. We train independent deep networks to virtually stain and segment grayscale images of smears. The segmented images are then used to train a classifier to yield a quantitative five-part WBC differential. Results. Our virtual staining scheme accurately recapitulates the appearance of cells under conventional Giemsa staining, the gold standard in hematology. The trained cellular and nuclear segmentation networks achieve high accuracy, and the classifier can achieve a quantitative five-part differential on unseen test data. Conclusion. This proposed automated hematology analysis framework could greatly simplify and improve current complete blood count and blood smear analysis and lead to the development of a simple, fast, and low-cost, point-of-care hematology analyzer.

Objective. Initial performance evaluation of a system for simultaneous high-resolution ultrasound imaging and focused mechanical submillimeter histotripsy ablation in rat brains. Impact Statement. This study used a novel combination of high-resolution imaging and histotripsy in an endoscopic form. This would provide neurosurgeons with unprecedented accuracy in targeting and executing nonthermal ablations in minimally invasive surgeries. Introduction. Histotripsy is a safe and effective nonthermal focused ablation technique. However, neurosurgical applications, such as brain tumor ablation, are difficult due to the presence of the skull. Current devices are too large to use in the minimally invasive approaches surgeons prefer. We have developed a combined imaging and histotripsy endoscope to provide neurosurgeons with a new tool for this application. Methods. The histotripsy component had a 10 mm diameter, operating at 6.3 MHz. Affixed within a cutout hole in its center was a 30 MHz ultrasound imaging array. This coregistered pair was used to ablate brain tissue of anesthetized rats while imaging. Histological sections were examined, and qualitative descriptions of ablations and basic shape descriptive statistics were generated. Results. Complete ablations with submillimeter area were produced in seconds, including with a moving device. Ablation progress could be monitored in real time using power Doppler imaging, and B-mode was effective for monitoring post-ablation bleeding. Collateral damage was minimal, with a 100 μm maximum distance of cellular damage from the ablation margin. Conclusion. The results demonstrate a promising hardware suite to enable precision ablations in endoscopic procedures or fundamental preclinical research in histotripsy, neuroscience, and cancer.