Deep tissue volumetric optoacoustic tracking of individual circulating tumor cells in an intracardially perfused mouse model

Abstract

Widespread metastasis is the major cause of death from melanoma and other types of cancer. At present, the dynamic aspects of the metastatic cascade remain enigmatic. The feasibility to track circulating melanoma cells deep within living intact organisms can greatly impact our knowledge on tumor metastasis, but existing imaging approaches lack the sensitivity, spatio-temporal resolution or penetration depth to capture flowing tumor cells over large fields of view within optically-opaque biological tissues. Vast progress with the development of optoacoustic tomography technologies has recently enabled two- and three-dimensional imaging at unprecedented frame rates in the order of hundreds of Hertz, effectively mapping up to a million image voxels within a single volumetric snapshot. Herein, we employ volumetric optoacoustic tomography for real-time visualization of passage and trapping of individual B16 melanoma cells in the whole mouse brain. Detection of individual circulating melanoma cells was facilitated by substituting blood with an artificial cerebrospinal fluid that removes the strong absorption background in the optoacoustic images. The approach can provide new opportunities for studying trafficking and accumulation of metastatic melanoma cells in different organs.

Optoacoustic imaging of the skin

“…Propagation to other tissues at late stages is caused by tumour cells circulating in the bloodstream, also known as circulating tumour cells (CTCs), which are regarded as a potent indicator of malignancy with promising prognostic value in different types of cancer. Various OA sensing and imaging systems have been used to detect and track CTCs in mice and men, [106][107][108] such as B16 melanoma cells (Figure 4C). The metastatic spread of melanoma cells in sentinel lymph nodes of patients was also detected with commercial OAT systems.…”

“…B, Un-mixed bio-distributions of melanin, oxygenated and deoxygenated haemoglobin in basal cell carcinoma (BCC) patients 102. C, OAT visualization of circulating B16 melanoma cells being arrested in the capillary network of the mouse brain 108. D, Un-mixed volumetric bio-distributions of melanin and indocyanine green (ICG) in a metastatic sentinel lymph node of a melanoma patient Other dermatologic applications of optoacoustic (OA) imaging with the clinical horizon.…”

Photoacoustic Neuroimaging - Perspectives on a Maturing Imaging Technique and its Applications in Neuroscience

“…Circulating melanoma cells could be imaged in the brain of mice perfused with artificial cerebrospinal fluid, which was possible because melanoma cells naturally contain the highly absorbing pigment melanin. Still, high hemoglobin absorption prevented a transfer of the technique to in vivo detection (Deán-Ben et al, 2020). In addition to cell visualization, it is possible to successfully manipulate circulating B16F10 mouse melanoma cells with acoustic and photoacoustic pressure waves.…”

Silicon‐Photonics Point Sensor for High‐Resolution Optoacoustic Imaging

“…[ 2 ] Current state‐of‐the‐art piezoelectric sensor arrays employed in medical ultrasound and optoacoustic imaging offer resolutions of several hundreds of micrometers [ 3 ] which may not be sufficient for observations at the cellular level. [ 4,5 ] However, miniaturization comes at the cost of steep sensitivity loss, as the sensitivity of piezoelectric elements drops quadratically with element size. The resolution can be improved to several tens of micrometers by using acoustic lenses, [ 6 ] but at added manufacturing costs and complexity.…”