iThera Medical (Germany)

We review today's photonic systems (LD/LED/VCSEL/SSL) used for photoacoustic imaging and identify the major challenges to propel this technology into routine clinical use: a factor of 100 in cost, volume, and power consumption for photon generation must be reached. The photonic subsystem presented is based on a compact set-up of triple-junction 940nm and single-junction 850nm VCSEL arrays combined with bare ToF CMOS driver chips. We discuss the optomechanical set-up, the measured key parameters of individual VCSEL arrays and the manufactured VCSEL subsystem with 3.5kW optical peak power for pulse lengths from 10 to 100ns. Even at these high output powers, laser class 1 operation can be achieved. The integrated drivers from automotive LiDAR operate the VCSEL subsystem with a wall-plug efficiency of 25% at a repetition rate of 1kHz. The heat dissipation can be buffered in a small copper block, so the subsystem can directly be mounted within a medical handheld device with no active cooling. We discuss the target applications oxygenation and muscle perfusion for photoacoustic imaging using a combination of 760/800/850nm VCSEL arrays. This VCSEL-based subsystem can replace current photonic systems and is the game-changer for routine clinical use. In addition, the concept is scalable and paves the way towards future patch and sensor photoacoustic applications.

Photoacoustic imaging (PAI), also referred to as optoacoustic imaging, has shown promise in early-stage clinical trials in a range of applications from inflammatory diseases to cancer. While the first PAI systems have recently received regulatory approvals, successful adoption of PAI technology into healthcare systems for clinical decision making must still overcome a range of barriers, from education and training to data acquisition and interpretation. The International Photoacoustic Standardisation Consortium (IPASC) undertook an community exercise in 2022 to identify and understand these barriers, then develop a roadmap of strategic plans to address them. Here, we outline the nature and scope of the barriers that were identified, along with short-, medium- and long-term community efforts required to overcome them, both within and beyond the IPASC group.

ObjectivesExamination of lymph nodes is one of the most common indications for imaging in the head and neck region. The purpose of this study is to evaluate whether multispectral optoacoustic tomography can be used to observe chromophore differences between benign and malignant neck lymph nodes.Materials and methodsProof-of-concept ex vivo study of resected cervical lymph nodes from 11 patients. The examination of lymph nodes included imaging with hybrid ultrasound and multispectral tomography system followed by spectral unmixing to separate signals from the endogenous chromophores water, lipid, hemoglobin and oxygenated hemoglobin; calculation of semi-quantitative parameters (total hemoglobin and relative oxygenation of hemoglobin). Comparison of the results from the hybrid measurement with the histopathological results.ResultsMost patients suffered from squamous cell carcinoma (n = 7), also metastasis from salivary gland adenocarcinoma and papillary thyroid carcinoma, were included. The comparison between benign cervical lymph nodes and metastases showed significant differences for the absorbers water, lipid, hemoglobin and oxygenated hemoglobin and total hemoglobin.ConclusionsOur ex vivo study suggests that multispectral optoacoustic tomography can be used to detect differences between reactive lymph nodes and metastases. The measurement of endogenous chromophores can be used for this purpose. The examinations are non-invasively and thus potentially improve diagnostic prediction. However, potential influences from the ex vivo setting must be considered.

Breast cancer is a complex tumor type involving many biological processes. Most chemotherapeutic agents exert their antitumoral effects by rapid induction of apoptosis. Another main feature of breast cancer is hypoxia, which may drive malignant progression and confer resistance to various forms of therapy. Thus, multi-aspect imaging of both tumor apoptosis and oxygenation in vivo would be of enormous value for the effective evaluation of therapy response. Herein, we demonstrate the capability of a hybrid imaging modality known as multispectral optoacoustic tomography (MSOT) to provide high-resolution, simultaneous imaging of tumor apoptosis and oxygenation, based on both the exogenous contrast of an apoptosis-targeting dye and the endogenous contrast of hemoglobin. MSOT imaging was applied on mice bearing orthotopic 4T1 breast tumors before and following treatment with doxorubicin. Apoptosis was monitored over time by imaging the distribution of xPLORE-APOFL750©, a highly sensitive poly-caspase binding apoptotic probe, within the tumors. Oxygenation was monitored by tracking the distribution of oxy- and deoxygenated hemoglobin within the same tumor areas. Doxorubicin treatment induced an increase in apoptosis-depending optoacoustic signal of xPLORE-APOFL750© at 24 h after treatment. Furthermore, our results showed spatial correspondence between xPLORE-APO750© and deoxygenated hemoglobin. In vivo apoptotic status of the tumor tissue was independently verified by ex vivo fluorescence analysis. Overall, our results provide a rationale for the use of MSOT as an effective tool for simultaneously investigating various aspects of tumor pathophysiology and potential effects of therapeutic regimes based on both endogenous and exogenous molecular contrasts.

Skin tags are common and mostly benign, but occasionally contain skin cancers. This study analysed skin tags by combining three advanced optical imaging technologies: reflectance confocal microscopy (RCM), optical coherence tomography (OCT) and multispectral optoacoustic imaging (MSOT) supplemented by dermoscopy MATERIALS AND METHODS: A prospective clinical study recruiting patients with skin tags from a university hospital clinic over a 2-week period. OCT, RCM and MSOT imaging were performed prior to excisional biopsies. Image features such as pigmentation, cell types and skin architecture, angiographic information demonstrating vascular pattern were captured, analysed, and compared to melanin and haemoglobin content in MSOT as well as histopathology. Six patients with dermal naevi (2); compound naevi (3); neurofibroma (1) were included. All skin tags except the neurofibroma were pigmented (5/6), with sparse (5/6) and dense (4/6) hyperreflective nests and band-like collagen in dermis in 6/6 lesions on RCM. Dermoscopy showed dots (5/6) and coiled vessels (5/6). Linear vertical vessels were present in all OCT images. MSOT images consisted of a compact shell-like superficial melanin area, same shape and size as the skin tag, dermal vessels were visible in 4/5 naevi, HbO2 signal clearly demarcated blood vessels located below the melanin signal. OCT showed linear vessels in all lesions. Pigmentation was identified by RCM as benign nests of melanocytes. MSOT supplemented with spatial distribution of melanin and HbO2 that indicated all skin tags were benign with no infiltration of vessels inside the melanin signal. Each advanced method proved indispensable for fast diagnosis. Larger studies are warranted for validation.

Die mikrovaskuläre Dysfunktion stellt insbesondere im Frühstadium der Systemischen Sklerose (SSc) die zu Grunde liegende Pathophysiologie sowohl von kutanen wie auch Organmanifestationen dar und führt letztlich zu hoher Morbidität und Mortalität. Bisher ist deren quantitative Erfassung mit klinisch etablierten Bildgebungsmethoden nicht möglich. Wir haben geprüft, ob mittels eines Hybridsystems aus multispektraler optoakustischer Tomografie (MSOT) und Ultraschall die mikrovaskuläre Dysfunktion bei SSc im Frühstadium erfasst und evaluiert werden kann.

Multispectral optoacoustic tomography (MSOT) represents a new in vivo imaging technique with high resolution (~250μm) and tissue penetration (>1cm) using the photoacoustic effect. While ultrasound contains anatomical information for lesion detection, MSOT provides functional information based on intrinsic tissue chromophores. We aimed to evaluate the feasibility of combined ultrasound/MSOT imaging of breast cancer in patients compared to healthy volunteers. Imaging was performed using a handheld MSOT system for clinical use in healthy volunteers (n = 6) and representative patients with histologically confirmed invasive breast carcinoma (n = 5) and ductal carcinoma in situ (DCIS, n = 2). MSOT values for haemoglobin and oxygen saturation were assessed at 0.5, 1.0 and 1.5cm depth and selected wavelengths between 700 and 850nm. Reproducible signals were obtained in all wavelengths with consistent MSOT signals in superficial tissue in breasts of healthy individuals. In contrast, we found increased signals for haemoglobin in invasive carcinoma, suggesting a higher perfusion of the tumour and tumour environment. For DCIS, MSOT values showed only little variation compared to healthy tissue. This preliminary MSOT breast imaging study provided stable, reproducible data on tissue composition and physiological properties, potentially enabling differentiation of solid malignant and healthy tissue. • A handheld MSOT probe enables real-time molecular imaging of the breast. • MSOT of healthy controls provides a reproducible reference for pathology identification. • MSOT parameters allows for differentiation of invasive carcinoma and healthy tissue.