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Eigenspectra optoacoustic tomography achieves quantitative blood oxygenation imaging deep in tissues (1511.05846v1)

Published 18 Nov 2015 in physics.med-ph, cs.CV, physics.optics, and q-bio.QM

Abstract: Light propagating in tissue attains a spectrum that varies with location due to wavelength-dependent fluence attenuation by tissue optical properties, an effect that causes spectral corruption. Predictions of the spectral variations of light fluence in tissue are challenging since the spatial distribution of optical properties in tissue cannot be resolved in high resolution or with high accuracy by current methods. Spectral corruption has fundamentally limited the quantification accuracy of optical and optoacoustic methods and impeded the long sought-after goal of imaging blood oxygen saturation (sO2) deep in tissues; a critical but still unattainable target for the assessment of oxygenation in physiological processes and disease. We discover a new principle underlying light fluence in tissues, which describes the wavelength dependence of light fluence as an affine function of a few reference base spectra, independently of the specific distribution of tissue optical properties. This finding enables the introduction of a previously undocumented concept termed eigenspectra Multispectral Optoacoustic Tomography (eMSOT) that can effectively account for wavelength dependent light attenuation without explicit knowledge of the tissue optical properties. We validate eMSOT in more than 2000 simulations and with phantom and animal measurements. We find that eMSOT can quantitatively image tissue sO2 reaching in many occasions a better than 10-fold improved accuracy over conventional spectral optoacoustic methods. Then, we show that eMSOT can spatially resolve sO2 in muscle and tumor; revealing so far unattainable tissue physiology patterns. Last, we related eMSOT readings to cancer hypoxia and found congruence between eMSOT tumor sO2 images and tissue perfusion and hypoxia maps obtained by correlative histological analysis.

Citations (210)

Summary

  • The paper introduces eMSOT, which leverages PCA-derived eigenspectra to model light fluence and enable quantitative sO2 imaging deep within tissues.
  • The paper demonstrates up to a tenfold improvement in sO2 accuracy over conventional linear unmixing techniques through extensive simulations and experimental validations.
  • The paper validates eMSOT's noninvasive capability to resolve sO2 gradients in muscle and tumor tissues, aligning closely with histological markers of perfusion and hypoxia.

Quantitative Imaging of Blood Oxygenation with Eigenspectra Optoacoustic Tomography

The paper presents a novel method termed Eigenspectra Multispectral Optoacoustic Tomography (eMSOT), which offers quantitative imaging of blood oxygen saturation (sO2) deep within tissues. This approach addresses a fundamental challenge in optoacoustic imaging, namely the spectral corruption caused by wavelength-dependent light fluence attenuation in tissue. By modeling the light fluence spectrum with a small number of base spectra, eMSOT circumvents the need for detailed knowledge of tissue optical properties. This enables significant improvements over conventional methods in capturing tissue sO2 with high accuracy.

Theoretical and Experimental Framework

The researchers have discovered a principle that defines light fluence as an affine function of base spectra, independent of the distribution of tissue optical properties. This finding allows the eMSOT method to correct for spectral corruption, traditionally a major impediment in obtaining accurate deep tissue sO2 readings. Instead of relying on a detailed map of tissue optical properties, eMSOT uses Principal Component Analysis (PCA) to derive three significant base spectra, or eigenspectra, sufficient to model light fluence across various tissue conditions.

Validation involved extensive simulations (over 2000) and experiments on phantoms and animals, demonstrating that eMSOT can achieve up to a tenfold improvement in sO2 accuracy over traditional linear unmixing techniques. Specifically, the paper highlights the method's effectiveness in resolving sO2 gradients in muscle and tumor tissues—a capability previously only attainable through invasive procedures.

Empirical Insights and Implications

In empirical tests, eMSOT consistently outperformed linear unmixing, particularly in challenging scenarios involving deep tissues. The method provided high-fidelity sO2 images that aligned closely with histological assessments of perfusion and hypoxia. Notably, the variability in Eigenfluence parameters (m1, m2, and m3) effectively captured the differences in tissue depth and background oxygenation, contributing to the method's accuracy. For example, blood phantom experiments revealed eMSOT's capability to estimate sO2 with errors under 10%, compared to errors of up to 30% with conventional methods.

The paper also demonstrates eMSOT's utility in tumor hypoxia studies, where it was congruent with histological markers of perfusion and hypoxia. The method holds the potential to offer non-invasive alternatives for assessing tumor physiology and could be instrumental in clinical applications that require understanding tissue oxygenation status without the disadvantages of invasive techniques.

Future Directions and Application Prospects

eMSOT stands out for its potential to become a standard tool in both clinical and research settings. By reducing the dependency on direct measurement of tissue optical properties, it paves the way for more accessible assessments of blood and tissue oxygenation, especially valuable in fields like oncology, cardiology, and metabolic research. The method's congruence with clinically significant markers such as hypoxia could broaden its applicability in studies where longitudinal, non-invasive tissue analysis is essential.

Ongoing developments in fast, video-rate MSOT systems enhance the practical relevance of eMSOT, offering feasible real-time imaging solutions. Future work could expand its validation across diverse physiological scenarios, integrate it into operational clinical frameworks, and refine its computational efficiency. Additionally, extending eMSOT to simultaneous quantitative assessments of other physiological parameters represents an intriguing avenue for enhancing its diagnostic utility.

In summary, eMSOT presents a notable advancement for optoacoustic imaging, providing high-resolution, quantitative imaging of blood oxygenation in a non-invasive manner. Its adoption could vastly improve our capability to visualize and understand complex physiological and pathological processes across a range of medical fields.