The absorption of visible light by human skin is governed by a number of natural chromophores: Eumelanin, pheomelanin, oxyhemoglobin, and deoxyhemoglobin are the major absorbers in the visible range in cutaneous tissue. Label-free quantification of these tissue chromophores is an important step of optoacoustic (photoacoustic) imaging towards clinical application, since it provides relevant information in diseases. In tumor cells, for instance, there are metabolic changes (Warburg effect) compared to healthy cells, leading to changes in oxygenation in the environment of tumors. In malignant melanoma changes in the absorption spectrum have been observed compared to the spectrum of nonmalignant nevi. So far, optoacoustic imaging has been applied to human skin mostly in single-wavelength mode, providing anatomical information but no functional information. In this work, we excited the tissue by a tunable laser source in the spectral range from 413-680 nm with a repetition rate of 50 Hz. The laser was operated in wavelengthsweep mode emitting consecutive pulses at various wavelengths that allowed for automatic co-registration of the multispectral datasets. The multispectral raster-scan optoacoustic mesoscopy (MSOM) system provides a lateral resolution of <60 μm independent of wavelength. Based on the known absorption spectra of melanin, oxyhemoglobin, and deoxyhemoglobin, three-dimensional absorption maps of all three absorbers were calculated from the multispectral dataset.
The characterization of the degradation of surgical sutures (~500 μm diameter) up to ~9 mm in tissue phantoms and up to ~3 mm depth in euthanized mice, and its potential application in in vivo animals is demonstrated using a custom dark-field photo-acoustic microscope (PAM). By using a simple theoretical approach and modelling the characteristics of our ultrasound transducer, both theoretical and experimental observations are in good agreement. The implications of this work for industrial applications are discussed by comparing the measurements with an optical microscope and with a developed algorithm on tissue simulating phantoms and with ex vivo measurements using PAM.
Optoacoustic (photoacoustic) imaging has a high potential for imaging melanin-rich structures in skin and the microvasculature of the dermis due to the natural chromophores (de)oxyhemoglobin, and melanin. The vascular network in human dermis comprises a large network of arterioles, capillaries, and venules, ranging from 5 μm to more than 100 μm in diameter. The frequency spectrum of the microcirculatory network in human skin is intrinsically broadband, due to the large variety in size of absorbers. In our group we have developed raster-scan optoacoustic mesoscopy (RSOM) that applies a 100 MHz transducer with ultra-wide bandwidth in raster-scan mode achieving lateral resolution of 18 μm. In this study, we applied high frequency RSOM to imaging human skin in a healthy volunteer. We analyzed the frequency spectrum of anatomical structures with respect to depth and show that frequencies >60 MHz contain valuable information of structures in the epidermis and the microvasculature of the papillary dermis. We illustrate that RSOM is capable of visualizing the fine vascular network at and beneath the epidermal-dermal junction, revealing the vascular fingerprint of glabrous skin, as well as the larger venules deeper inside the dermis. We evaluate the ability of the RSOM system in measuring epidermal thickness in both hairy and glabrous skin. Finally, we showcase the capability of RSOM in visualizing benign nevi that will potentially help in imaging the penetration depth of melanoma.
Fluorescence diffuse optical tomography (fDOT) is a noninvasive imaging technique that makes it possible to quantify the spatial distribution of fluorescent tracers in small animals. fDOT image reconstruction is commonly performed by means of iterative methods such as the algebraic reconstruction technique (ART). The useful results yielded by more advanced l 1 -regularized techniques for signal recovery and image reconstruction, together with the recent publication of Split Bregman (SB) procedure, led us to propose a new approach to the fDOT inverse problem, namely, ART-SB. This method alternates a cost-efficient reconstruction step (ART iteration) with a denoising filtering step based on minimization of total variation of the image using the SB method, which can be solved efficiently and quickly. We applied this method to simulated and experimental fDOT data and found that ART-SB provides substantial benefits over conventional ART.
Reconstruction algorithms for imaging fluorescence in near infrared ranges usually normalize fluorescence light with respect to excitation light. Using this approach, we investigated the influence of absorption and scattering heterogeneities on quantification accuracy when assuming a homogeneous model and explored possible reconstruction improvements by using a heterogeneous model. To do so, we created several computer-simulated phantoms: a homogeneous slab phantom (P1), slab phantoms including a region with a two- to six-fold increase in scattering (P2) and in absorption (P3), and an atlas-based mouse phantom that modeled different liver and lung scattering (P4). For P1, reconstruction with the wrong optical properties yielded quantification errors that increased almost linearly with the scattering coefficient while they were mostly negligible regarding the absorption coefficient. This observation agreed with the theoretical results. Taking the quantification of a homogeneous phantom as a reference, relative quantification errors obtained when wrongly assuming homogeneous media were in the range +41 to +94% (P2), 0.1 to −7% (P3), and −39 to +44% (P4). Using a heterogeneous model, the overall error ranged from −7 to 7%. In conclusion, this work demonstrates that assuming homogeneous media leads to noticeable quantification errors that can be improved by adopting heterogeneous models.