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Engineering Concerns for a Portable NIRS Device

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When designing a portable Near-Infrared Spectroscopy (NIRS) device for the measurement of muscle oxygenation, design engineers have plenty of factors to consider. They must think about battery life, portability, affordability, safety, and many other design criteria. Before considering many of these criteria, however, an engineer must design a working technology that is capable of actually measuring muscle oxygenation. Without this basic attribute, the device would be a complete failure. The basics for measurement of relative oxygenated and deoxygenated hemoglobin concentrations was introduced previously in the patent blog post, but the engineering design problem was mostly glossed over. This post will dive a little deeper into the quantitative nature of measurement of muscle oxygenation and what functions the design engineer must consider when designing a device that will operate properly and accurately. The main question to be answered is: how does an engineer use light to measure concentration of a particle in muscle?

Fig 1: Molecular Absorption Coefficient Profiles for Oxygenated and Deoxygenated Hemoglobin

As mentioned before, NIRS works by measuring the absorbance or attenuation of light as it passes through a sample to make a measurement of concentration of the absorbing analyte or particle. Also previously introduced were the benefits of using near-infrared light since it can pass through biological tissue and is primarily absorbed by hemoglobin. In an ideal world the absorbance is defined by the Beer-Lambert Law. According to this law, the absorbance of a particle is equal to the natural log of incident light over the detected light and this is further equal to the product of the molar absorbance coefficient, the concentration of the particle, and the mean path length of detected photons. In an ideal case this law works because it describes when light is shown through a glass cuvette with a solution with only one absorbance particle, but this is not helpful for a NIRS device for muscle oxygenation. Thus, for a NIRS device, the modified Beer-Lambert Law must be used, which is the same as the original equation but with an extra scattering term to account for photon scatter when passing through tissue like skin and muscle (Eqn. 1).

Here A is absorbance, I0 is incident (transmitted) light, I is detected light, ɛ is molar absorbance coefficient, c is concentration, L is mean path length, and G is the scattering term. This is great in theory because it appears that concentration can be calculated relatively easily, but there are further problems to solve. Start by considering the knowns and unknowns. The absorbance coefficient is a known value for any analyte given the wavelength of the laser used (Fig. 1), and the path length can easily be found from the distance between the light emitter and detector with some regards to the path shape which is known to be roughly banana shaped. This leaves two unknown terms: the unknown that to be measured, i.e. concentration, and the scatter term. The scatter term is unfortunately a problem. It varies by tissue and considering the device should be designed for consumers to use on different locations, different muscles, and different amounts of say fat that may lie in the way of the muscle, this G term will forever be changing. Thus, there needs to be a way to get rid of it. The easiest way to do this is to find change in absorbance so that G will be subtracted away. This uses the assumption that G is constant for a given location. The resulting equation will then give change in concentration as it is the only factor that changed between measurements 1 and 2 (usually an initial measurement and a second measure at a later time) (Eqn. 2). Notice that absorbance is now equal to the natural log of the first intensity detected divided by the second intensity measured based on the identity (log(x/y) = log(x)-log(y). Note that the need to get rid of G, because it cannot be calculated on every single consumer, leads to the fact that NIRS devices almost always measure change in concentration or relative concentration when measuring muscle oxygenation.

This equation looks great. So change in concentration as opposed to exact concentration is found, but so what, this is still a very helpful measure for oxygenation during exercise. BUT, this equation is not the whole story. NIRS works by measuring both oxygenated and deoxygenated hemoglobin (Hb). Both species of Hb contribute to absorbance in the near-infrared range. Thus the equation actually looks like this (Eqn. 3)

In this equation, subscript O is used for oxygenated Hb, and subscript Hb is used for deoxygenated Hb. Now there are two unknowns and only one equation. So what does a smart engineer do? They add more lights. By measuring multiple wavelengths, two changes in absorbance can be measured allowing both concentrations to be calculated by solving the system of equation (Eqn. 4-5).

In these equations, superscripts refer to the wavelengths of light 1 and 2. It must be remembered that absorbance coefficient, absorbance change, and path length will all vary based on wavelength. This clearly allows for the output of relative concentrations or total blood oxygen saturation percentage (oxyHb / [oxyHb + deoxyHb]). Here the assumption is that total Hb is equal to oxyHb plus deoxyHb. The last piece of the puzzle for an engineer is to decide on what wavelengths should be used for the lights. This is a very impactful decision in building the algorithm to calculate the outcome measures of the device since ɛ, A, and L all depend on wavelength. It should be noted based on Figure 1 that certain wavelengths will be better than others. For example, if 805 nm light is used, then the absorbance coefficients for both species of Hb will be the same. This leads to irrational answers for Equations 4 and 5, so this wavelength should be avoided. The best case is to pick a wavelength above and below this so that one is more sensitive to oxyHb and the other is more sensitive to deoxyHb. Thus, using 750 and 850nm could be viable options, and these are used in several current devices.

These results allow an engineer to design a device that will properly measure muscle oxygenation through the relative concentrations of oxygenated and deoxygenated Hb. A reminder that some of the assumptions that needed to be made were that the tissue was homogenous, that oxy and deoxy Hb are the only particles contributing to absorbance, that absorbance is constant in time when Hb concentrations do not change, that the scattering term remained constant, and that oxy + deoxy Hb is the total Hb. Realistically, tissue is not homogeneous, but this assumption causes smaller errors in the volumes being considered close to the skin surface. Unfortunately, Hb is not the only chromophore contributing to absorbance. Fat is a major problem because it shares a similar range of wavelengths for absorbance. Some devices take fat correction into account, but other do not, and papers have pointed this out. It is reasonable to assume that absorbance is constant in time when concentration is constant, but pulsatile flow can cause error here. The scattering term should remain constant if the position of the device is not changed, and it is also reasonable to assume that there are not Hb species besides oxy and deoxy in the muscle. Some of these do cause limitations to the design described here, and as already mentioned it will only measure change in concentration not the absolute value. In conclusion, two wavelengths of light are needed measure muscle oxygenation with NIRS.

 

References

[1]. Shimadzu Commercial Website https://www.ssi.shimadzu.com/products/imaging/labnirs-principle-of-operation.html

[2]. Kocsis, L., Herman, P., & Eke, A. (2006). The modified Beer-Lambert law revisited. Physics in Medicine and Biology, 51(5). http://doi.org/10.1088/0031-9155/51/5/N02

[3]. Len-Carrin, J., & Len-Domnguez, U. (2012). Functional Near-Infrared Spectroscopy (fNIRS): Principles and Neuroscientific Applications. Neuroimaging – Methods. http://doi.org/10.5772/23146

[4]. McManus, C. J., Collison, J., & Cooper, C. E. (2018). Performance comparison of the MOXY and PortaMon near-infrared spectroscopy muscle oximeters at rest and during exercise. Journal of Biomedical Optics, 23(01), 1. http://doi.org/10.1117/1.jbo.23.1.015007

Using NIRS to non-invasively monitor muscle oxygenation during exercise

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Skeletal muscles are the basis of all movement in the human body, and athletes work years to train their muscles to be powerful yet efficient. Even if a single muscle could allow a person to lift a car, it would not be very useful if the muscle could no longer create forceful contraction again for several hours. The muscle also must be efficient in the use of oxygen, ions, and other substrates that allow for contraction to be able to quickly recover and be prepared for repeated contraction. Muscle oxygenation is particularly important for both endurance and power of a muscle because it is necessary to produce ATP to power muscle cells to contract. Heart rate and blood oxygen delivery are helpful for getting an idea of an athlete’s efficiency, but they do not tell the whole story for the muscle. At the muscle, the balance between delivery and consumption of oxygen explains its efficiency [1]. To measure muscle oxygen saturation, a technique called near-infrared spectroscopy (NIRS) is used to get real time data to inform athletes of the state of their muscles during training. This is a powerful tool for maximizing athletic gains in muscles from training and to see the state of the muscle over time and after rest.

Early NIRS instrumentation was contained to the lab, but recently portable versions have become more common, which is very important for its use in both the medical and research fields. In medicine, NIR has been used for study of septic shock, free tissue transfer, real-time tissue perfusion during surgery, cancer nanotechnology, and peripheral arterial disease.  For this post, the use of NIR in exercise will be highlighted. In exercise, NIRS is a great tool because it is a non-invasive method that can be applied locally to muscles or tissues of interest and provide real time data during exercise. NIRS is highly sensitive to changes in muscle tissue oxygenation [2, 3, 4], and it reflects the balance between oxygen delivery and utilization, unlike measurements of arterial or venous blood samples which have been used previously and are minimally invasive [2]. NIRS works by measuring the percentage of oxygenated hemoglobin to total hemoglobin (oxygenated and deoxygenated hemoglobin) to give muscle oxygenation. Hemoglobin is the main oxygen carrying protein in the blood and can carry 4 oxygen molecules (O2). Oxygenated and deoxygenated hemoglobin scatter NIR light (600-1000 nm) differently, so their relative concentrations can be found from their molecular absorption coefficients. To do this, three to four different wave lengths of light will be used to determine the concentrations of each based on the change in molecular absorption coefficients at different wavelengths (Fig 1). NIR light must be used as it: 1) passes through skin, bone, and most biological tissue, and 2) is the appropriate wavelength where the small amount of absorption that occurs is predominately from hemoglobin (Fig 2) [5].  As the muscle performs work, the muscle oxygenation will decrease as a function of the work and the training of the muscle.

Fig. 1: Molecular Absorption Coefficient Profiles for Oxygenated and Deoxygenated Hemoglobin [5]

Fig 2: Light Absorption by Wavelength [5]

 

 

 

 

 

 

 

 

 

 

A patent on google patent claims to leverage this technology in a wearable article of clothing for athletes to be able to measure muscle oxygenation real-time (Fig 3) [6]. The patent claims to be a method and apparatus for assessing tissue oxygenation saturation through two main claims that summarize to: a portable apparatus that is a wearable article capable of measuring oxygenation saturation of at least one of a skin dermis layer, adipose layer, or muscular fascial layer of a user during physical activity using at least one near-infrared spectroscopy probe including at least one near-infrared light source and at least one photodetector. In short, the patent is a claim on a portable, wearable NIRS device for tissue oxygenation levels. NIRS has been a research method for decades, so the novel part of this patent lies in the incorporation of this technology into a wearable article of clothing.

Fig 3: Figure from patent illustrating wearable shirt, shorts, and socks using NIRS

Fig4: Figures from patent showing example data of muscle oxygenation average during constant rate running at different grades (top) and real time data from medial gastrocnemius muscle during weighted exercise and unweighted control (bottom)

This patent pertains primarily to the measurement of tissue during exercise (Fig 4). This could be of use for athletes during training to be able to compare what levels of exercise cause certain levels of muscle oxygen saturation loss. For example, highly trained athletes often train at high altitude to reduce oxygen in the air so that their body adapts to becoming more efficient with oxygen usage. This prompts higher performance when returning to normal oxygen levels. Using NIRS could allow them to find a training regime that caused the same hypoxia in muscle without traveling to higher altitude (they will still miss out on some of the pulmonary and cardio vascular advantages that training at altitude can produce). This may also be helpful in rehabilitation as the change in muscle oxygenation is an indicator that the muscle is being used and can inform physical therapists if the patient is engaging the correct muscles during rehab. Additionally, the device may also have merit in the medical realm for monitor muscle oxygenation in patients with chronic heart failure, peripheral vascular disease, chronic obstructive pulmonary disease, and varying muscle diseases [3, 4].

  1. Patent title: Method and apparatus for assessing tissue oxygenation saturation
  2. Patent number: US20170273609A1
  3. Patent filing date: 2017-03-22
  4. Patent issue date: Patent Pending
  5. How long it took for this patent to issue: TBD
  6. Inventor(s): Luke G. Gutwein, Clinton D. Bahler, Anthony S. Kaleth
  7. Assignee (if applicable): Indiana University Research and Technology Corp
  8. U.S. classification: A61B5/0075
  9. How many claims: 20

References and Further Reading

[1] BSX Athletics https://support.bsxinsight.com/hc/en-us/articles/204468695-What-is-muscle-oxygenation-

[2] Bhambhani, Y. N. (2004). Muscle Oxygenation Trends During Dynamic Exercise Measured by Near Infrared Spectroscopy. Can. J. Appl. Physiol., 29(4), 504–523.

[3] Hamaoka, T., Mccully, K. K., Quarisma, V., Yamamoto, K., & Chance, B. (2007). Near-infrared spectroscopy / imaging for monitoring muscle oxygenation and oxidative metabolism. Jounal of Biomedical Optics, 12(6), 1–16. http://doi.org/10.1117/1.2805437

[4] Boushel, R., & Piantadosi, C. A. (2000). Near-infrared spectroscopy for monitoring muscle oxygenation. Acta Physiol Scand, 168, 615–622. http://doi.org/10.1046/j.1365-201x.2000.00713.x

[5] Shimadzu Commercial Website https://www.ssi.shimadzu.com/products/imaging/labnirs-principle-of-operation.html

[6] Patent https://patents.google.com/patent/US20170273609A1/en?oq=US20170273609A1

[7] Ferrari, M., Muthalib, Makii, & Quarisma, V. (2011). The use of near-infrared spectroscopy in understanding skeletal muscle physiology : Phil. Trans. R. Soc. A, 369, 4577–4590. http://doi.org/10.1098/rsta.2011.0230 

[8] Artinis Commercial Site https://www.artinis.com/portamon#portamon-software