Eigenspectra optoacoustic tomography achieves quantitative blood oxygenation imaging deep in tissues

Abstract

Light propagating in tissue attains a spectrum that varies with location due to wavelength-dependent fluence attenuation, an effect that causes spectral corruption. Spectral corruption has limited the quantification accuracy of optical and optoacoustic spectroscopic methods, and impeded the goal of imaging blood oxygen saturation (sO2) deep in tissues; a critical goal for the assessment of oxygenation in physiological processes and disease. Here we describe light fluence in the spectral domain and introduce eigenspectra multispectral optoacoustic tomography (eMSOT) to account for wavelength-dependent light attenuation, and estimate blood sO2 within deep tissue. We validate eMSOT in simulations, phantoms and animal measurements and spatially resolve sO2 in muscle and tumours, validating our measurements with histology data. eMSOT shows substantial sO2 accuracy enhancement over previous optoacoustic methods, potentially serving as a valuable tool for imaging tissue pathophysiology.

Advanced optoacoustic methods for multiscale imaging of in vivo dynamics

“…In multispectral imaging applications, one further faces the challenge of the so-called ‘spectral coloring’. Due to the non-local and non-linear dependence of the light fluence distribution on the optical properties of the object [355], spectra of various tissue chromophores and agents, extracted by means of optoacoustics, might be corrupted [113]. For improving quantitative determination of chromophore concentrations, the light distribution in tissue needs to be accurately accounted for [356].…”

“…Since many diseases undergo structural changes at time scales ranging from days to weeks and months, imaging can be used to visualize and quantify these changes. For example, vascular structures can be mapped for depths of millimetres to centimetres within mammalian tissues [13] and accurate estimation of oxygen saturation is possible with proper models of light attenuation [113]. Due to the strong intrinsic haemoglobin contrast, optoacoustics represents a valuable tool to study the evolution of important hallmarks of cancer such as angiogenesis [53, 114] and hypermetabolism [115, 116].…”

Toward whole-body quantitative photoacoustic tomography of small-animals with multi-angle light-sheet illuminations

“…the Monte Carlo simulation. Besides, multispectral PAT applications in near-infrared window should also be studied in the future work, such as estimating blood oxygen level in vivo [40], and improving quantitative determination of the concentrations of chromophores using the q-PAT scheme to fully consider the wavelength-dependent light fluence attenuation with depth [12,41].…”

“…Thus, there is a pressing need to develop quantitative PAT (q-PAT), mainly focusing on quantifying the distribution of optical properties inside tissues from the c-PAT results [9,10]. Accordingly, q-PAT can also accurately obtain concentrations of endogenous and exogenous chromophores (hemoglobin, melanin, fluorescence agent, nanoparticle, etc) based on their spectral specificity and multiwavelength measurements, so that the morphological, functional and molecular information of biological tissues can be simultaneously provided [11][12][13][14].…”

Correlation between volumetric oxygenation responses and electrophysiology identifies deep thalamocortical activity during epileptic seizures

“…Note that the linear unmixing approach may suffer from inaccuracies due to wavelengthdependent light attenuation thus generating quantitative errors when it comes to estimating the spatial distribution of oxygenated and deoxygenated hemoglobin, especially in deep tissues. 27 However, we are primarily interested in the relative temporal dynamics of the oxygenation profiles and the corresponding delays in the thalamocortical loops, which are not affected by the quantitative errors in estimating the chromophore concentrations.…”