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Biocompatible gold nanoparticles designed to absorb light at wave-lengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance–ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function.

The combination of an ultrathin bronchoscope, navigational technology, and endobronchial ultrasound (EBUS) seems to combine the best of mutual abilities for evaluating peripheral pulmonary lesions, but ultrathin bronchoscopes that allow the use of EBUS have not been developed so far. To compare the diagnostic yield of transbronchial biopsy under EBUS, fluoroscopy, and virtual bronchoscopic navigation guidance using a novel ultrathin bronchoscope with that using a thin bronchoscope with a guide sheath for peripheral pulmonary lesions. In four centers, patients with suspected peripheral pulmonary lesions less than or equal to 30 mm in the longest diameter were included and randomized to undergo transbronchial biopsy with EBUS, fluoroscopy, and virtual bronchoscopic navigation guidance using a 3.0-mm ultrathin bronchoscope (UTB group) or a 4.0-mm thin bronchoscope with a guide sheath (TB-GS group). A total of 310 patients were enrolled and randomized, among whom 305 patients (150, UTB group; 155, TB-GS group) were analyzed. The ultrathin bronchoscope could reach more distal bronchi than the thin bronchoscope (median fifth- vs. fourth-generation bronchi; P < 0.001). Diagnostic histologic specimens were obtained in 74% (42% for benign and 81% for malignant lesions) of the UTB group and 59% (36% for benign and 70% for malignant lesions) of the TB-GS group (P = 0.044, Mantel-Haenszel test). Complications including pneumothorax, bleeding, chest pain, and pneumonia occurred in 3% and 5% in the respective groups. The diagnostic yield of the UTB method is higher than that of the TB-GS method. Clinical trial registered with www.umin.ac.jp/ctr/ (UMIN 000003177).

Depression is a major psychological disorder with a growing impact worldwide. Traditional methods for detecting the risk of depression, predominantly reliant on psychiatric evaluations and self-assessment questionnaires, are often criticized for their inefficiency and lack of objectivity. Advancements in deep learning have paved the way for innovations in depression risk detection methods that fuse multimodal data. This paper introduces a novel framework, the Audio, Video, and Text Fusion-Three Branch Network (AVTF-TBN), designed to amalgamate auditory, visual, and textual cues for a comprehensive analysis of depression risk. Our approach encompasses three dedicated branches—Audio Branch, Video Branch, and Text Branch—each responsible for extracting salient features from the corresponding modality. These features are subsequently fused through a multimodal fusion (MMF) module, yielding a robust feature vector that feeds into a predictive modeling layer. To further our research, we devised an emotion elicitation paradigm based on two distinct tasks—reading and interviewing—implemented to gather a rich, sensor-based depression risk detection dataset. The sensory equipment, such as cameras, captures subtle facial expressions and vocal characteristics essential for our analysis. The research thoroughly investigates the data generated by varying emotional stimuli and evaluates the contribution of different tasks to emotion evocation. During the experiment, the AVTF-TBN model has the best performance when the data from the two tasks are simultaneously used for detection, where the F1 Score is 0.78, Precision is 0.76, and Recall is 0.81. Our experimental results confirm the validity of the paradigm and demonstrate the efficacy of the AVTF-TBN model in detecting depression risk, showcasing the crucial role of sensor-based data in mental health detection.

The introduction of combined modality single photon emission computed tomography (SPECT)/CT cameras has revived interest in quantitative SPECT. Schemes to mitigate the deleterious effects of photon attenuation and scattering in SPECT imaging have been developed over the last 30 years but have been held back by lack of ready access to data concerning the density of the body and photon transport, which we see as key to producing quantitative data. With X-ray CT data now routinely available, validations of techniques to produce quantitative SPECT reconstructions have been undertaken. While still suffering from inferior spatial resolution and sensitivity compared to positron emission tomography (PET) imaging, SPECT scans nevertheless can be produced that are as quantitative as PET scans. Routine corrections are applied for photon attenuation and scattering, resolution recovery, instrumental dead time, radioactive decay and cross-calibration to produce SPECT images in units of kBq.ml −1 . Though clinical applications of quantitative SPECT imaging are lacking due to the previous non-availability of accurately calibrated SPECT reconstructions, these are beginning to emerge as the community and industry focus on producing SPECT/CT systems that are intrinsically quantitative.

We demonstrate the use of cryogenic super-resolution correlative light and electron microscopy (csCLEM) to precisely determine the spatial relationship between proteins and their native cellular structures. Several fluorescent proteins (FPs) were found to be photoswitchable and emitted far more photons under our cryogenic imaging condition, resulting in higher localization precision which is comparable to ambient super-resolution imaging. Vitrified specimens were prepared by high pressure freezing and cryo-sectioning to maintain a near-native state with better fluorescence preservation. A 2-3-fold improvement of resolution over the recent reports was achieved due to the photon budget performance of screening out Dronpa and optimized imaging conditions, even with thin sections which is at a disadvantage when calculate the structure resolution from label density. We extended csCLEM to mammalian cells by introducing cryo-sectioning and observed good correlation of a mitochondrial protein with the mitochondrial outer membrane at nanometer resolution in three dimensions.

Esophageal cancer is becoming increasingly prevalent in Western countries. Early detection is crucial for effective treatment. Multimodal imaging combining optical coherence tomography (OCT) with complementary optical imaging techniques may provide enhanced diagnostic capabilities by simultaneously assessing tissue morphology and biochemical content. We aim to develop a tethered capsule endoscope (TCE) that can accommodate a variety of point-scanning techniques in addition to OCT without requiring design iterations on the optical or mechanical design. We propose a TCE utilizing exclusively reflective optics to focus and steer light from and to a double-clad fiber. Specifically, we use an ellipsoidal mirror to achieve finite conjugation between the fiber tip and the imaging plane. We demonstrate a functional all-reflective TCE. We first detail the design, fabrication, and assembly steps required to obtain such a device. We then characterize its performance and demonstrate combined OCT at 1300 nm and visible spectroscopic imaging in the 500- to 700-nm range. Finally, we discuss the advantages and limitations of the proposed design. An all-reflective TCE is feasible and allows for achromatic high-quality imaging. Such a device could be utilized as a platform for testing various combinations of modalities to identify the optimal candidates without requiring design iterations.

Many cognitive processes require communication between the neocortex and the hippocampus. However, coordination between large-scale cortical dynamics and hippocampal activity is not well understood, partially due to the difficulty in simultaneously recording from those regions. In the present study, we developed a flexible, insertable and transparent microelectrode array (Neuro-FITM) that enables investigation of cortical–hippocampal coordinations during hippocampal sharp-wave ripples (SWRs). Flexibility and transparency of Neuro-FITM allow simultaneous recordings of local field potentials and neural spiking from the hippocampus during wide-field calcium imaging. These experiments revealed that diverse cortical activity patterns accompanied SWRs and, in most cases, cortical activation preceded hippocampal SWRs. We demonstrated that, during SWRs, different hippocampal neural population activity was associated with distinct cortical activity patterns. These results suggest that hippocampus and large-scale cortical activity interact in a selective and diverse manner during SWRs underlying various cognitive functions. Our technology can be broadly applied to comprehensive investigations of interactions between the cortex and other subcortical structures. Liu et al. present a flexible, insertable and transparent microelectrode (FITM) array termed Neuro-FITM. Multimodal recordings with Neuro-FITM reveal diverse and selective large-scale cortical activation patterns associated with hippocampal sharp-wave ripples.

Raman spectroscopy and Fourier transform infrared (FTIR) spectroscopy are powerful analytical techniques widely used separately in different fields of study. Integrating these two powerful spectroscopic techniques into one device represents a groundbreaking advance in multimodal imaging. This new combination which merges the molecular vibrational information from Raman spectroscopy with the ability of FTIR to study polar bonds, creates a unique and complete analytical tool. Through a detailed examination of the microscope’s operation and case studies, this article illustrates how this integrated analytical instrument can provide more thorough and accurate analysis than traditional methods, potentially revolutionising analytical sample characterisation. This article aims to present the features and possible uses of a unified instrument merging FTIR and Raman spectroscopy for multimodal imaging. It particularly focuses on the technological progress and collaborative benefits of these two spectroscopic techniques within the microscope system. By emphasising this approach’s unique benefits and improved analytical capabilities, the authors aim to illustrate its applicability in diverse scientific and industrial sectors.

Our understanding of mechanotransduction in mammalian inner ears remains incomplete, in part due to imaging limitations: current systems cannot simultaneously provide high-resolution images needed for subcellular analysis and the deep focus required for structural mechanics. Optical coherence tomography (OCT) enables structural and vibrational imaging through the bone of the intact cochlea in models such as mice, supporting studies of cochlear mechanics in animals with functional hearing. However, capturing both cellular ( ) and structural ( ) details requires rapid switching between optical configurations with numerical apertures ranging from 0.13 to 0.8. A spectral-domain OCT system combined with two-photon fluorescence microscopy (TPM) and interchangeable objectives could overcome this challenge, enabling high-precision vibration and fluorescence imaging across multiple scales in a single experiment. We aim to develop an integrated OCT and two-photon microscope optimized for imaging the morphology and function of the cochlea. We integrated a custom SD-OCT/TPM system into an upright microscope with a high-precision stage for animal positioning. The system uses two tunable liquid lenses to form a beam expander, enabling dynamic adjustment of the beam diameter at the back aperture of each objective. This optimized light throughput and maintained a high signal-to-noise ratio (SNR) across all objectives. In addition, we automated optical adjustments to facilitate seamless imaging with a wide range of objectives. For each objective, we measured the SNR difference between a beam expanded to match the largest back aperture and a beam adjusted to match the back aperture of the objective. Except for the objective, the measured SNR improvements closely matched theoretical predictions. Using four selected objectives spanning the required numerical aperture (NA) range, we successfully imaged excised murine cochlea samples, obtaining relevant structural information across scales. In living murine models, we used TPM to locate fluorescent outer hair cells and make vibrometry measurements through the round window membrane. We found that hair cells, the basilar membrane, and the reticular lamina moved in phase in response to a 70 kHz stimulus at 90 dB SPL, consistent with expected cochlear mechanics. Automation and optimization of the optical system enabled seamless multiscale imaging of the murine cochlea, providing high-quality morphological, functional, and two-photon fluorescence images. The dynamic adjustment of the beam diameter within the microscope was essential for maintaining high SNR across a wide range of numerical apertures.

Structural and molecular imaging of the developing embryo can provide deep insights into the development of various pathologies, but few techniques enable the simultaneous detection of these parameters. We demonstrate the first use of combined optical coherence tomography and two-photon light sheet fluorescence microscopy (2P-LSFM) for simultaneous structural and molecular imaging. We aim to develop a multimodal high-resolution embryonic system that facilitates simultaneous structural and molecular embryonic imaging. We have developed a multimodal imaging system in which the optical coherence tomography (OCT) and light sheet illumination beams were optically co-aligned and scanned through the galvanometer-mounted mirrors and the same illumination objective. The swept-source OCT system provides a lateral resolution of and an axial resolution of . The 2P-LSFM light sheet thickness was , and the transverse resolution was . We have demonstrated the system's capabilities using fluorescent microbeads and fluorescently tagged mouse embryos. The co-alignment of the OCT and 2P-LSFM systems enables simple image registration and high-throughput multimodal imaging.