Lung cancer remains one of the most life-threatening diseases and is currently managed through invasive approaches such as surgery, chemo- or radiotherapy. In this work, we introduce a novel method for the targeted delivery of a therapeutic laser for the treatment of tumors in peripheral areas of the lungs. The approach uses a 2.4 mm diameter, ultra-soft, patient-specific magnetic catheter delivered from the end of a standard bronchoscope to reach the periphery of the lungs. Integrated shape sensing facilitates supervised autonomous full-shape control for precise navigation into the sub-segmental bronchi, and an embedded laser fiber allows for treatment via localized energy delivery. We report the complete navigation of eight primary lumina in the bronchi of an anatomically accurate phantom (developed from computed tomography (CT) data) and successful laser delivery for photothermal ablation. We further evaluate the approach in three diverse branches of excised cadaveric lungs, showing a mean improvement in navigation depth of 37% with less tissue displacement when compared to a standard semi-rigid catheter and navigation depth repeatability across all tests of <1 mm.

Gold nanorods (AuNRs) can be synthesised with different sizes but similar aspect ratios and therefore similar surface plasmon resonances (SPRs). Their strong optical absorbance governed by their SPRs facilitates their ability to be used as molecular-targeted contrast agents for photoacoustic (PA) imaging. The size of AuNRs has an effect on the PA conversion efficiency, melting threshold, and cytotoxicity, indicating that size can have a significant impact on overall biomedical efficacy. We investigated these factors for four different AuNRs (widths of 10, 25, 40 and 50 nm) all with SPRs of 815 ± 26 nm. A size-dependent linear relationship between fluence and PA amplitude was observed, along with particle melting. Reshaping was confirmed via transmission electron microscopy and spectrophotometry at a laser fluence of 11 ± 1.7 mJ cm⁻², 20 ± 2.2 mJ cm⁻², and 40 ± 2.6 mJ cm⁻². Cytotoxicity was tested on lung cancer cells (A549) via a colourimetric assay at a maximum concentration of 3 × 10¹⁰ NP ml⁻¹. Results demonstrate the 40 nm and 50 nm AuNRs produced the highest signal for equivalent particle numbers, but displayed the highest toxicity. Conversely, the 10 nm AuNRs were the most efficient photoacoustic converters, at equivalent total mass. This study demonstrates the importance of AuNR size and concentration on selection of AuNRs for their eventual clinical use.

Lung ultrasound (LUS) has emerged as a safe and cost-effective modality for assessing lung health, particularly during the COVID-19 pandemic. However, interpreting LUS images remains challenging due to its reliance on artefacts, leading to operator variability and limiting its practical uptake. To address this, we propose a deep learning pipeline for multi-class segmentation of objects (ribs, pleural line) and artefacts (A-lines, B-lines, B-line confluence) in ultrasound images of a lung training phantom. Lightweight models achieved a mean Dice Similarity Coefficient (DSC) of 0.74, requiring fewer than 500 training images. Applying this method in real-time, at up to 33.4 frames per second in inference, allows enhanced visualisation of these features in LUS images. This could be useful in providing LUS training and helping to address the skill gap. Moreover, the segmentation masks obtained from this model enable the development of explainable measures of disease severity, which have the potential to assist in the triage and management of patients. We suggest one such semi-quantitative measure called the B-line Artefact Score, which is related to the percentage of an intercostal space occupied by B-lines and in turn may be associated with the severity of a number of lung conditions. Moreover, we show how transfer learning could be used to train models for small datasets of clinical LUS images, identifying pathologies such as simple pleural effusions and lung consolidation with DSC values of 0.48 and 0.32 respectively. Finally, we demonstrate how such DL models could be translated into clinical practice, implementing the phantom model alongside a portable point-of-care ultrasound system, facilitating bedside assessment and improving the accessibility of LUS.

Gold nanorods (AuNRs) have the potential to be used in photoacoustic (PA) imaging and plasmonic photothermal therapy (PPTT) due to their unique optical properties, biocompatibility, controlled synthesis, and tuneable surface plasmon resonances (SPRs). Conventionally, continuous-wave (CW) lasers are used in PPTT partly due to their small size and low cost. However, if pulsed-wave (PW) lasers could be used to destroy tissue then combined theranostic applications, such as PA-guided PPTT, would be possible using the same laser system and AuNRs. In this study, we present the effects of AuNR size on PA response, PW-PPTT efficacy, and PA imaging in a tissue-mimicking phantom, as a necessary step in the development of AuNRs towards clinical use. At equivalent NP/mL, the PA signal intensity scaled with AuNR size, indicating that overall mass has an effect on PA response, and reinforcing the importance of efficient tumour targeting. Under PW illumination, all AuNRs showed toxicity at a laser fluence below the maximum permissible exposure to skin, with a maximum of 80% cell-death exhibited by the smallest AuNRs, strengthening the feasibility of PW-PPTT. The theranostic potential of PW lasers combined with AuNRs has been demonstrated for application in the lung.

High intensity focused ultrasound (HIFU) or focused ultrasound surgery is a non-invasive technique for the treatment of cancerous tissue, which is limited by difficulties in getting real-time feedback on treatment progress and long treatment durations. The formation and activity of acoustic cavitation, specifically inertial cavitation, during HIFU exposures has been demonstrated to enhance heating rates. However, without the introduction of external nuclei its formation an activity can be unpredictable, and potentially counter-productive. In this study, a combination of pulse laser illumination (839 nm), HIFU exposures (3.3 MHz) and plasmonic gold nanorods (AuNR) was demonstrated as a new approach for the guidance and enhancement of HIFU treatments. For imaging, short duration HIFU pulses (10 μs) demonstrated broadband acoustic emissions from AuNR nucleated cavitation with a signal-to-noise ranging from 5-35 dB for peak negative pressures between 1.19-3.19 ± 0.01 MPa. In the absence of either AuNR or laser illumination these emissions were either not present or lower in magnitude (e.g. 5 dB for 3.19 MPa). Continuous wave (CW) HIFU exposures for 15 s, were then used to generate thermal lesions for peak negative pressures from 0.2-2.71 ± 0.01 MPa at a fluence of 3.4 mJ [Formula: see text]. Inertial cavitation dose (ICD) was monitored during all CW exposures, where exposures combined with both laser illumination and AuNRs resulted in the highest level of detectable emissions. This parameter was integrated over the entire exposure to give a metric to compare with measured thermal lesion area, where it was found that a minimum total ICD of [Formula: see text] a.u. was correlated with the formation of thermal lesions in gel phantoms. Furthermore, lesion area (mm2) was increased for equivalent exposures without either AuNRs or laser illumination. Once combined with cancer targeting AuNRs this approach could allow for the future theranostic use of HIFU, such as providing the ability to identify and treat small multi-focal cancerous regions with minimal damage to surrounding healthy tissue.