Expanding the medical spectral window v8

Improving Non-Invasive Blood Analysis by

Expanding the Medical Spectral Window

Katherine Paseman

Background: 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

Scattering Hematocrit Low- Blood loss,High - Dehydration

Absorption/Transmittance

Hgb ConcentrationSpO2

AnemiaBlood Loss

Background: Beer-Lambert Law

Optical approaches leverage the Beer-Lambert law which models the intensity of light entering (Ii) and exiting (Io) a sample using 3

variables,

t – Sample thickness – cm

c – Concentration of absorbent - g/liter Note: 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.Note: Blood’s ε(λ) is very large for λ < 600 nm (red) so it absorbs a lot of light below this wavelength. This is why a flashlight (white light) shone through your finger only transmits red light.

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

Example: Pulse Oximetry

Webster, JG. Design of Pulse Oximeters

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

• A Pulse Oximeter non-invasively determines pulse and blood oxygenation with photodiodes using differential light absorption

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

Problem we address: Samsung Hgb/Hct Monitor has >8% error

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]

Medical SpectralWindow

600 to 1000 nm

Note: 569 nm lies outside the

MedicalSpectralWindow

Problem we address: Samsung Hgb/Hct Monitor has >8% error

Our Hypothesis: Targeting Thumb Webbing vs. Index Finger Mitigates Measurement Error

The Beer-Lambert Law explains that decreasing sample thickness should result in an increase in transmittance.

This allows us to get better absorption measurements

• Increases the signal which decreases noise based error.

• Allows us to detect additional sources of error.

The Apparatus We created an adjustable clip

that fits either the 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 both 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.

Experiment 2: Approach

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.

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

Edge of MSW

ArtifactAmplification

Amplificationoutside MSW

Noise

-10000

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10000

20000

30000

40000

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33273.000 counts

Index Finger


-10000

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Index Finger


60534.000 counts


-5000

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Data: 569 nm Subject 1 Webbing

Thumb Webbing


32847.801 counts

Less Noise Edge of MSW

Amplificationoutside MSW

Artifact SizeReduction

-10000

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Thumb Webbing


60849.000 counts

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Thumb Webbing


55602.750 counts


Experiment 2: Data Summary 569 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

Experiment 2: Findings

The signal is less noisy going through the thumb webbing versus the finger

Amplification through thumb webbing is significantly better, but the exact ratio varies from subject to subject.

A spike at ~610 nm for all the finger readings could either be an artifact or simply the edge of the medical spectral window

“Artifact Amplification” was apparent in this experiment as well

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

1. Our hypothesis is confirmed: transmission through thumb webbing is better.1

2. “Artifact Amplification” was confirmed by both experiments and will be a key design consideration going forward.2

3. 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.

1,2 Both phenomena would partially explain Samsung’s error numbers.

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

Further Research: Fluorescence

59 yr old male

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

Expanding the medical spectral window v8

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