Image processing and miniaturized optics promise enhanced hemoglobin sensing

10 Aug 2022

University of Cambridge review indicates strengths and weaknesses of current technology.

Optical techniques for imaging hemoglobin, whether to precisely map blood vessels or monitor blood oxygenation levels, have advanced rapidly as ways to exploit interactions between the hemoglobin molecules and incident light have been developed.

Clinical advances have included the ability of photoacoustic imaging (PAI) to be used as a screening tool for breast cancer, thanks to its ability to image the blood vessels of a tumor, and the use of mobile health applications via smartphones to monitor hemoglobin outside the clinic.

A study led by Sarah Bohndiek at the University of Cambridge and published in SPIE Journal of Biomedical Optics has reviewed the optical tools available for noninvasive hemoglobin sensing and imaging, indicating the key limitations in the current state-of-the-art and routes to advance the clinical use of the technology.

Techniques considered by the study included pulse oximetry, spectral reflectance imaging, diffuse optical imaging, spectroscopic optical coherence tomography, photoacoustic imaging and diffuse correlation spectroscopy.

Pulse oximetry, in which LEDs at two different wavelengths are used to identify the absorption coefficients of oxy- and deoxyhemoglobin and compare them as a biomarker, is a well-established clinical first-response technique, although it is known to be less accurate when used on darker skins.

The technique has, however, come to the fore during the Covid-19 pandemic, with pulse oximeters being used to monitor and treat respiratory conditions affecting blood oxygenation levels. The report commented that the inherent limitations of the method should be studied further, given the potential for long-term and widespread use of pulse oximetry in Covid-19 patient management.

Standards and practices

The advantage of both PAI and diffuse optical imaging (DOI) techniques over pulse oximetry is their ability to provide depth-resolved imaging, potentially up to and beyond depths of 1 centimeter. However, "although these methods have been widely explored in the clinical research setting, they are only just beginning to find routine application in the clinic for patient management," noted the survey.

"A key challenge for PAI is biomarker quantification. During reconstruction, a number of assumptions are made including the speed of sound in tissue, transducer impulse response, detection bandwidth, and continuous sampling. If these assumptions break down, for example due to heterogeneities in tissue due to air cavities, there will be distortions in the image."

Calibration and clinical quality assurance methods for PAI are still under development, said the report, particularly through community-led efforts.

DOI is based on exploiting the scattering properties of tissue, a factor which hinders most other imaging operations. The study authors commented that DOI nonetheless has limited spatial resolution and often requires reference to other modalities such as MRI or CT for analysis. Standardization of DOI systems for clinical translation is currently ongoing, particularly for breast cancer detection.

New dimension of knowledge from optical technologies

"The acceptability and relevance of new hemoglobin sensing and imaging technologies to clinicians will be driven by various factors, including cost, complexity, and physical size of the systems, as well as the ease of use and data interpretation," said the report, which noted acceptance of pulse oximetry has already made the clinical community well aware of blood oxygenation as a biomarker.

Miniaturization of light sources, optical components and cameras will reduce the costs of newer optical techniques and mitigate some of their current technical limitations, while advances in image processing and neural networks will help to extract valuable results from the optical data.

"Hemoglobin imaging techniques add a new dimension of knowledge in a range of clinical settings," concluded the report. "Emerging technologies are well placed to further enhance these areas of existing clinical practice, but are also likely to contribute to the decentralization of healthcare, both to tertiary care centers and through the deployment of wearable technologies for self-monitoring in the home."

Noninvasive Hemoglobin Sensing and Imaging: Optical Tools for Disease Diagnosis is available in Journal of Biomedical Optics.