Expanding the medical spectral window v7

Improving Non-Invasive Blood Analysis by Expanding the Medical

Spectral Window

Katherine Paseman

Goal: Detect Medical Problems by non-Invasively Measuring Optical Properties of Blood

Optical Blood Property

Medical Diagnostic (Symptom)

Example Problem

Fluorescence Zinc Protoporphyrin (ZPP) Concentration

Iron Deficient Anemia, Lead Poisoning

Absorption Hemoglobin Concentration

Anemia

Scattering Hematocrit Low- Blood loss,High - Dehydration

Beer-Lambert Law

Optical approaches leverage the Beer-Lambert law which uses 3 variables to model light entering (Ii) and exiting (Io) a sample.

Io = Ii 10 –2.303 ε(λ) c t /(64,500 g Hb/mole)

t – Sample thickness – cm c – concentration of absorbent - g/liter (A typical

value of c for whole blood is 150 g Hb/liter.) ε(λ) – extinction coefficient of absorbent, which

is a function of the light’s wavelength.– Blood’s ε(λ) is very large for λ < 600 nm– This is why a flashlight shone through the hand only

transmits red light.

Prior Work: Pulse Oximetry

A Pulse Oximeter non-invasively determines Pulse and Blood Oxygenation using differential light absorption.

A Photodiode measures light intensity of Red (660nm) & Infrared (940 nm) LEDs shone through a finger during systole/diastole.

Blood Oxygenation is a function of the “Ratio of Ratios” of Light Intensities at these points.

Webster, JG. Design of Pulse Oximeters

Prior Work: Masimo pt 1

Most non-invasive blood sensors extend the pulse oximeter’s differential absorption trick. Like the pulse oximeter, they target the finger using wavelengths above 600 nm, the so called ”Medical Spectral Window”, to collect enough light.

λnm

Hb02 ε(λ)cm-1/M

Hb ε(λ)cm-1/M

610 1506 9443.6

620 942 6509.6

630 610 5148.8

660 319.6 3226.56

700 290 1794.28

730 390 1102.2

805 844 730.28

905 1209.2 769.8

Source: Masimo [US7377794]

Prior Work: Masimo pt 2

MedicalSpectralWindow

Prior Work: Samsung pt 1

Samsung’s work states “Three variables of R569,805, R569,940, and R569,975 were used for calibration and prediction models.” producing this comment by one author:

G Yoon <[email protected]> - “569nm is highly absorbing in tissue and, at the same time, 569nm intensity is small compared with that at longer wavelength. That is why you may not get good signal. We used a custom-made LED array that has several chips of 569nm to increase intensity.”

λ Hb02 ε(λ)cm-1/M

Hb ε(λ)cm-1/M

569 44496 45072

660 319.6 3226.56

805 844 730.28

940 1214 693.44

975 1144 389.288

Samsung reported >8% error forHemoglobin [Jeong et. Al. 2002] and Hematocrit [Yoon et. al. 2005].

mailto:[email protected]

Prior Work: Samsung pt 2

MedicalSpectralWindow

569 nm lies outside the MedicalSpectralWindow

Our Research: Target Thumb Webbing for Absorption instead of Finger

Our hypothesis: We can extend the medical spectral window by offsetting the increase in extinction coefficient at λ< 600 nm with a decrease in sample thickness

[Sabrina Paseman 2008] did this by targeting the thumb webbing for fluorescence measurements.

We do this for absorption. This allows us to get better

absorption measurements by increasing the signal and so decreasing noise based error.

It also allows us to detect additional sources of error.

The Apparatus

We created an adjustable width clip that fits either the subject’s index finger or thumb webbing.

One end of the clip holds the same 5-LED package used by Samsung and the other holds a fiber optic cable which connects to an Avantes AvaSpec-2048 spectrometer.

The LEDs and spectrometer are controlled by an Arduino microcontroller.

This allows us to double check the LED’s wavelength, determine LED intensity, see if there are any LED artifacts (emissions at wavelengths besides the primary wavelength), and observe any swamping or fluorescing effects.

Experiment 1: Approach

A clamp is adjusted to fit the subject’s index finger. The subject removes their finger so that the

spectrometer/LED distance can be measured with a micrometer.

The thumb webbing is placed over the entire LED. The spectrometer auto-adjusts the integration time

to a full scale reading and the data is collected. The subject removes their thumb webbing and places

their index finger over the LED. The data is collected with the same integration time and plotted on the same axis for comparison.

Experiment 1: Data569 nm Subject 1

Thumb webbing

Index Finger

Integration Time: 404.05 ms

54054.5 counts

4131.5 counts

Width: 0.7175 cm

Experiment 1: Findings

General: Transmission increased 13 fold. Artifacts: Samsung’s LED chip has an artifact at

around 875nm when the 569nm LED is lit. If Samsung’s device uses a photodiode to collect light, especially at low intensities, much of the collected light would come from the artifact rather than the 569nm peak.

Race: This method limited the quality of the readings we could take from subjects with darker skin.

Age: Young people have smaller thumb webbing than older people.

Hold LED underneath the thumb webbing and the spectrometer on the other side.

Let the spectrometer auto-integrate and capture the graph.

For data analysis, find the ratio between the ratios of the peak counts at 569nm and the integration time.

Experiment 2: Approach

Countsthumb webbing

Integration timethumb webbing

Countsindex finger

Integration timeindex finger

Absorption Amplification =

-10000

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Data: 569 nm Subject 1 Finger

Index Finger


13640.500 counts

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Data: 569 nm Subject 1 Webbing

Thumb Webbing


32847.801 counts

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33273.000 counts

Index Finger

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Thumb Webbing


60849.000 counts

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Index Finger


60534.000 counts

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Thumb Webbing


55602.750 counts

Experiment 2: Data Summary569 nm

Subject Scopetw

(ADC Counts)

Integrationtw

(ms)Scopeif

(ADC Counts)

Integrationif

(ms)Ampli-fication

1 32847.801 99.70 13640.500 3097.90 74.825

2 60849.000 208.91 33273.000 1736.15 15.198

3 55602.750 114.73 60534.000 3808.11 30.488

Subject1: 58 years old - light skinnedSubject2: 52 years old - dark skinnedSubject3: 16 years old - light skinned

Key Finding:“Artifact Amplification”

Why does the artifact size increase? Blood is a low pass filter, attenuating small λ

(high frequencies) more than large λ. LED Artifacts (usually) appear “above” (at a

larger λ) the primary emission λ. If the LED’s primary λ is below 600 nm and the

artifact is above, the artifact will appear differentially amplified.

This amplification is a key consideration when designing with LEDs that have this characteristic.

Conclusions

Transmission through thumb webbing is at least 13x better than through the finger, but the exact ratio varies from subject to subject.

“Artifact Amplification” was confirmed by both experiments and will be a key design consideration going forward.

Both phenomena would partially explain Samsung’s error numbers.

Low readings from people with darker skin in the first experiment and smaller thumb webbing for younger subjects indicate that probe design will be a key issue going forward.

Further Research

See if there is a statistically significant difference between the light absorption of systolic and diastolic blood at 569, 660, 805, 940 and 975 nm.

Correlate more medical problems to absorption differentials and fluorescent phenomena.

– See if there is a statistically significant difference between the fluorescence of systolic and diastolic blood excited at 425 nm.

Collect data for more subjects with varying melanin contents and ages

References

[Sabrina Paseman 2008] Paseman, Sabrina. The Ferrometer: A Device to Detect Iron Deficient Anemia via Non-Invasive Optical Measurement of Zinc Protoporphyrin. Issue brief no. SO499. Los Angeles: University of Southern California, 2008. PDF file.

[US7377794] "Multiple Wavelength Sensor Interconnect” – p57 lists Masimo’s wavelengths

[Yoon et. Al. 2005] Yoon, Gilwon, Ph.D, et al. "Development of a Compact Home Health Monitor for Telemedicine." TELEMEDICINE AND e-HEALTH 11.6 (2005): 660-67. PDF File.

[Jeong et. Al. 2002] Jeong, Kye Jin, Su-Jin Kim, and Kun Kook Park. "Noninvasive Total Hemoglobin Measurement." Journal of Biomedical Optics 7.1 (2002): 45-50. PDF file.

“Tabulated Molar Extinction Coefficient for Hemoglobin in Water” http://omlc.ogi.edu/spectra/hemoglobin/summary.html

Documents

Expanding the medical spectral window v7