Pushing the boundaries of optoacoustic microscopy by total impulse response characterization.

Optical microscopy improves in resolution and signal-to-noise ratio by correcting for the system's point spread function; a measure of how a point source is resolved, typically determined by imaging nanospheres. Optical-resolution optoacoustic (photoacoustic) microscopy could be similarly corrected, especially to account for the spatially-dependent signal distortions induced by the acoustic detection and the time-resolved and bi-polar nature of optoacoustic signals. Correction algorithms must therefore include the spatial dependence of signals' origins and profiles in time, i.e. the four-dimensional total impulse response (TIR). However, such corrections have been so far impeded by a lack of efficient TIR-characterization methods. We introduce high-quality TIR determination based on spatially-distributed optoacoustic point sources (SOAPs), produced by scanning an optical focus on an axially-translatable 250 nm gold layer. Using a spatially-dependent TIR-correction improves the signal-to-noise ratio by >10 dB and the axial resolution by ~30%. This accomplishment displays a new performance paradigm for optoacoustic microscopy.

Non-invasive Measurement of Brown Fat Metabolism Based on Optoacoustic Imaging of Hemoglobin Gradients.

Metabolism is a fundamental process of life. However, non-invasive measurement of local tissue metabolism is limited today by a deficiency in adequate tools for in vivo observations. We designed a multi-modular platform that explored the relation between local tissue oxygen consumption, determined by label-free optoacoustic measurements of hemoglobin, and concurrent indirect calorimetry obtained during metabolic activation of brown adipose tissue (BAT). By studying mice and humans, we show how video-rate handheld multi-spectral optoacoustic tomography (MSOT) in the 700-970 nm spectral range enables non-invasive imaging of BAT activation, consistent with positron emission tomography findings. Moreover, we observe BAT composition differences between healthy and diabetic tissues. The study consolidates hemoglobin as a principal label-free biomarker for longitudinal non-invasive imaging of BAT morphology and bioenergetics in situ. We also resolve water and fat components in volunteers, and contrast MSOT readouts with magnetic resonance imaging data.

Multispectral Optoacoustic Tomography (MSOT) of Human Breast Cancer.

Purpose: In a pilot study, we introduce fast handheld multispectral optoacoustic tomography (MSOT) of the breast at 28 wavelengths, aiming to identify high-resolution optoacoustic (photoacoustic) patterns of breast cancer and noncancerous breast tissue.Experimental Design: We imaged 10 female patients ages 48-81 years with malignant nonspecific breast cancer or invasive lobular carcinoma. Three healthy volunteers ages 31-36 years were also imaged. Fast-MSOT was based on unique single-frame-per-pulse (SFPP) image acquisition employed to improve the accuracy of spectral differentiation over using a small number of wavelengths. Breast tissue was illuminated at the 700-970 nm spectral range over 0.56 seconds total scan time. MSOT data were guided by ultrasonography and X-ray mammography or MRI.Results: The extended spectral range allowed the computation of oxygenated hemoglobin (HBO2), deoxygenated hemoglobin (HB), total blood volume (TBV), lipid, and water contributions, allowing first insights into in vivo high-resolution breast tissue MSOT cancer patterns. TBV and Hb/HBO2 images resolved marked differences between cancer and control tissue, manifested as a vessel-rich tumor periphery with highly heterogeneous spatial appearance compared with healthy tissue. We observe significant TBV variations between different tumors and between tumors over healthy tissues. Water and fat lipid layers appear disrupted in cancer versus healthy tissue; however, offer weaker contrast compared with TBV images.Conclusions: In contrast to optical methods, MSOT resolves physiologic cancer features with high resolution and revealed patterns not offered by other radiologic modalities. The new features relate to personalized and precision medicine potential. Clin Cancer Res; 23(22); 6912-22. ©2017 AACR.

Flow-mediated dilatation test using optoacoustic imaging: a proof-of-concept.

Label-free multispectral optoacoustic tomography (MSOT) has recently shown superior performance in visualizing the morphology of human vasculature, especially of smaller vessels, compared to ultrasonography. Herein, we extend these observations towards MSOT interrogation of macrovascular endothelial function. We employed a real-time handheld MSOT scanner to assess flow-mediated dilatation (FMD), a technique used to characterize endothelial function. A data processing scheme was developed to quantify the dimensions and diameter changes of arteries in humans and determine wall distensibility parameters. By enabling high-resolution delineation of the blood-vessel wall in a cross-sectional fashion, the findings suggest MSOT as a capable alternative to ultrasonography for clinical FMD measurements.

Imaging of fatty tumors: appearance of subcutaneous lipomas in optoacoustic images.

A wide variety of subcutaneous soft-tissue masses may be seen in clinical practice. Clinical examination based on palpation alone is often insufficient to identify the nature and exact origin of the mass, in which case imaging is necessary. We used handheld multispectral optoacoustic imaging technology (MSOT) in a proof-of-principle study to image superficial fatty tumors and compare the images with diagnostic ultrasound. Fatty tumors were clearly visualized by MSOT and exhibited a spectral signature which differed from normal fatty tissue or muscle tissue. Our findings further indicated that MSOT offers highly complementary contrast to sonography. Based on the performance achieved, we foresee a promising role for MSOT in the diagnosis and evaluation of subcutaneous soft-tissue masses. Picture: Pseudo-color representation of a cross-sectional multi-spectral optoacoustic slice through a subcutaneous lipoma. Multi-spectral information is encoded in color. The lipoma can clearly be distinguished from the surrounding tissue based on its color. Scalebar 1 cm.

DNA-Nanostructure-Gold-Nanorod Hybrids for Enhanced In Vivo Optoacoustic Imaging and Photothermal Therapy.

A functional cancer theranostic nanoplatform is developed, specifically tailored toward the optoacoustic modality by combining gold nanorods with DNA nanostructures (D-AuNR). DNA origami is used as an efficient delivery vehicle owing to its prominent tumor-targeting property. The D-AuNR hybrids display an enhanced tumor diagnostic sensitivity by improved optoacoustic imaging and excellent photothermal therapeutic properties in vivo.

Multispectral opto-acoustic tomography of exercised muscle oxygenation.

Unlike near-infrared spectroscopy, multispectral opto-acoustic tomography (MSOT) has the potential to offer high-resolution imaging assessment of hemodynamics and blood saturation levels in muscle. However motion artifacts impede the real-time applications of the technique. We developed fast-MSOT with motion tracking that reduces motion artifacts. We used this algorithm to follow blood oxygenation level changes associated with muscle exercise in the muscle and the skin of healthy volunteers.