Frequency Domain Near-Infrared Spectroscopy. Clinical Applications for the Study of the Oxygenation and Hemodynamics of the Brain and Muscle

(1)

Frequency Domain Near-Infrared

Spectroscopy. Clinical Applications for the Study of the Oxygenation and Hemodynamics of

the Brain and Muscle

Antonios Michalos, M.D., M.S.

Director of Medical Research ISS, Inc.

Senor Research Scientist

UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN Beckman Institute for Advanced Science and Technology

Department of Mechanical Science and Engineering Department of Physics

E-mail: antonios.michalos@iss.com

(2)

OUTLINE



Frequency Domain Multidistance NIRS

• Instrumentation

 OxiplexTS

 Multidistance Sensors



FAQs and Answers



Applications

• Neurovascular surgery

• ICU post operative monitoring

• Obstructive Sleep Apnea Syndrome

• Age correlated changes

• Attention Deficit Hyperactivity Disorder

• Activation of Brain Areas

• Muscle Hemodynamic Changes in PVD

(3)

NIRS nel Dominio delle Frequenze.

Applicazioni Cliniche della Spetroscopia e Ossimetria del Cervello e del Muscolo

Emitter Detector

Reflected Collected

Absorbed

Light in

(4)

Why Near-Infrared Spectroscopy?



Non-invasive



Non-ionizing



Comfortable



Portable



Cost effective



Fast



Reliable



Real-time monitoring

of tissue oxygenation and hemodynamics

(5)

Why Frequency Domain Near-Infrared Spectroscopy of Biological Tissues

FD-NIRS separates absorption from scattering to obtain absolute values of hemoglobin concentration and tissue oxygen saturation

Main NIRS parameters:



Oxygenated hemoglobin, [O

₂

Hb]



Deoxygenated hemoglobin, [HHb]



Total hemoglobin, [tHb] = [O

₂

Hb]+ [HHb]



Tissue oxygenation, SO

₂

=[O

₂

Hb]/[tHb]

(6)

Frequency-Domain Tissue Oximeter

(Developed at LFD-UIUC, Built by ISS Inc., Champaign, IL, USA).

Modulation Frequency: 110 MHz

Light sources: 8 laser diodes at 690 nm 8 laser diodes at 830 nm

(electronically multiplexed at 40Hz) Detectors: 2 photomultiplier tubes

(7)

Multi distance Method

Dual Sensor Probe

(for bilateral frontal lobe measurements)

Light source fibers Detector fiber

Detector fibers:1 per channel (3 mm internal diameter)

Source fibers:4 pairs of fibers (emitting 690 nm and 830 nm respectively) per channel

Source-detector distance: Range 2-4 cm (multi-distance approach)

(8)

Cerebral hemodynamic

changes during voluntary hypoxia

Altered Hemodynamic responses to breath holding in subject with severe cardiovascular disease.

Decrease in [HHb]

Increase in [O2Hb]

Hemodynamic responses to breath holding in a healthy individual

Increase in [O²Hb]

Decrease in [HHb]

Healthy subject

Cardiovascular patient

(9)

Questions from the medical community:



Does the FD-NIRS and the multidistance approach probe the brain?



Which are the appropriate source-detector distances?



What proof can we give that the findings are not influenced by the superficial tissues.

Experimental approaches:



Brain vascular responsiveness to voluntary hypoxia with and without partial scalp ischemia.



Clamping of external and internal carotid arteries

during neurovascular surgery

(10)

Light source fibers Detector fiber

Partial scalp ischemia induced by a head tourniquet

(11)

a)

Breath Holding Exercises on 11 healthy volunteers

Without tourniquet With tourniquet

Whole array SDD 1.08 cm-4.38 cm

10 15 20 25 30 35 40 45

100 120 140 160 180

time, s

[tHb], [O2Hb],[HHb], m M/l

-2 -1 0 1 2 3 4

RS, A.U.

Respiratory Signal [tHb]

[O 2 Hb]

[HHb] ₁₀¹⁵

20 25 30 35 40 45

780 800 820 840 860

time, s

[tHb], [O2Hb],[HHb], m M/l

-2 -1 0 1 2 3 4

RS, A.U.

[tHb]

[O 2 Hb]

Respiratory Signal [HHb]

c) b)

SDD

1.08 cm-1.98 cm

(Superficial Tissues)

SDD

1.98 cm-4.38 cm

(Deep Tissues)

10 14 18 22 26 30 34 38

100 120 140 160 180

time, s [tHb], [O2Hb],[HHb],m M/l

-5 -4 -3 -2 -1 0 1

RS, A.U.

Respiratory Signal

[tHb]

[O Hb] 2 [HHb]

10 15 20 25 30 35 40 45

100 120 140 160 180

time, s [tHb], [O2Hb],[HHb],m M/l

-2 -1 0 1 2 3 4

RS, A.U.

[tHb]

2

[HHb]

Respiratory Signal

[O Hb]

(12)

Clamping of External vs. Internal Carotid Artery

in a Patient with Defective Left to Right Brain Vascular Anastomotic Communication during Neurovascular Surgery

(13)

NORMAL BRAIN ARTERIAL

CIRCULATION

(14)

External Carotid Artery Clamping

No change brain oxygenation and hemodynamics

(15)

Internal Carotid Artery Clamping

Significant changes in brain oxygenation and Hemodynamics

(16)

Conclusions

 Brain vascular response to hypoxia with and without partial scalp ischemia.

 Clamping of external and internal carotids during neurovascular surgery

Q. Does the FD-NIRS and multidistance approach probe the brain?

A. By measuring light simultaneously at multiple distances we reduce the contribution of the superficial layer. Optical properties of the superficial layer have no influence on time-of-flight.

Q. Which are the appropriate source-detector distances?

A. Light collected at 2-4 cm travels deeper into tissue and reaches the surface of the brain.

Q. Is our method working?

A. By looking at the details of brain hemodynamics during ischemia we differentiated spatial and temporal hemodynamic changes in the brain.

(17)

NIRS in Neurosurgery and ICU Post-Operative monitoring

University of Illinois at Chicago Medical Center Chicago, Illinois

(18)

Overall Trace

(19)

Monitoring of Brain Oxygenation

and Hemodynamics after Surgery

(20)

Near-Infrared Brain Oximetry in Obstructive Sleep Apnea Syndrome

University of Illinois at Urbana Champaign Laboratory for Fluorescence Dynamics

ISS Inc., Champaign, Illinois

Carle Foundation Hospital-Sleep Center Urbana , ^Illinois

University of Illinois at Chicago Medical Center

Center of Sleep and Ventilatory Disorders

(21)

Sleep apnea.

The cessation of airflow through the nose and mouth during sleep that lasts for more than 10 seconds.

Sleep apnea syndrome (SAS). At least 30 apneic episodes observed during a 7-hour sleep period.

SAS types: 1. Obstructive (OSAS) 2. Central

3. Mixed

 24% of males and 9% of females have 5 or more apneas per hour

 12% of men and 5% of women present more severe forms (more than 15 apneas per hour)

 OSAS in middle age adults has been identified in approximately 4% of men and 2% in women

 In elderly estimates range from 28% to 67% in men and 20% to 54% in women

(22)

Sleep apnea: Risks

 Social and professional impairment

 Traffic and work accidents

 Cardiovascular/pulmonary complications a. Systemic hypertension

b. Pulmonary hypertension c. Cardiac arrhythmias

d. Ischemic heart disease

e. Alteration of the vascular wall

 Cerebrovascular complications

a. Neuropsychological dysfunction b. Cognitive deficits

c. Transient ischemic attacks d. Strokes

 Death

(23)

POLYSOMNOGRAPHY

(sleep study)

Monitoring of:

Snoring

Respiratory effort Naso-oral airflow Recordings of:

Electrocardiogram (EKG)

Electroencephalogram (EEG)

Bilateral electro-oculogram (EOG)

Bilateral anterior tibialis Electromyogram (EMG) Submental electromyogram (EMG)

Arterial oximetry

But………it does not provide the clinician with information on cerebral oxygenation and hemodynamics, which are important parameters one wishes to determine.

(24)

Measurement protocol



Breath holding exercises

• 3-4 min baseline

• breath holding at FRC with resumption of breathing (3-5 times)

• 5-10 min baseline recovery

• Repetition of breath holding and

resumption of breathing (3-5 times)



NIRS measurements during sleep

(25)

Changes in cerebral hemodynamics with respect to baseline values

-3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20time, s 40

D[O2Hb], D[HHb], mmol/L

Respiratory signal, AU

D[HHb]

D[O2Hb]

OSA subject

Decrease in [O2Hb]

Increase in [HHb]

-3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20 40 time, s

D[O2Hb], D[HHb], mmol/L Respiratory signal, AU D[O2Hb]

D[HHb]

Changes in [O2Hb] and [HHb]

due to intermittent sleep apnea OSA subject

BREATH HOLDING

-3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20 40 time, s

D[O2Hb], D[HHb], mmol/L Respiratory signal, AU D[O2Hb]

D[HHb]

Control non-snorer

Increase in [O2Hb]

Decrease in [HHb]

DIURNAL NAPPING

-3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20 time, s 40

D[O2Hb], D[HHb], mmol/L Respiratory signal, AU

D[HHb]

D[O2Hb]

Opposite-phase changes in [O2Hb] and [HHb] due to vasomotion and

regular breathing Control non-snorer

-3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20 40 time, s

Snorer

D[HHb]

D[O2Hb]

Opposite-phase changes in [O2Hb] and [HHb] due to vasomotion and irregular

breathing

-3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20 time, s 40

Snorer

D[O2Hb]

D[HHb]

Delayed increase in [O2Hb]

Slight decrease in [HHb]

(26)

 Capillaries are the "heart" of the circulatory system, all the action is in the capillaries, and all other blood vessels

merely assist them.

 The blood flow across the capillary bed is regulated by a sphincter muscle on the arteriole side. Whenever there is little need to

supply blood to a given capillary bed, the sphincter closes and blood bypasses the capillary bed via an arterio-venal shunt.

 The cerebrovascular response to hypoxia (decreased O2) and hypercapnia (increased CO2) is vasodilation and opening of the capillary bed.

(27)

9 subjects (3716 years) 52 breath holdings

(25 11 s) 12 subjects (3810 years)

72 breath holdings (30 19 s)

8 subjects (4916 years) 58 breath holdings

(18 7 s)

(28)

Changes in total hemoglobin concentration during breath holding

Voluntary Breath Holding Duration, s -1

0 1 2 3 4 5 6 7 8 9

0 20 40 60 80 100 120

Breath Hold Duration, s

Change in tHb concentration, μmol/L

1

2

1 - area of tHb changes observed for control subjects 2 - area of tHb changes observed for OSAS subjects

0.60.9 22.315.8

OSAS

(8 subjects/ 8sessions/ 26 breath holds)

2.92.3 42.024.1

Controls

(8 subjects/ 8sessions/ 31 breath holds)

d[tHb]

dt

Change in tHb concentration,

μmol/L Duration of the

breath holding, s

Subjects

(matched in number, age and sex)

(29)

Changes in brain tissue total hemoglobin concentration (changes in cerebral blood volume)

1 - area of changes in control non-snorers 2 - area of changes in OSA sufferers

-2 0 2 4 6 8

Breath holding duration, s

Change in [t Hb], μ mol/L

0 20 40 60 80

1

2

(30)

65 70 75 80 85 90 95 100

1200 1250 1300 1350 1400

time, s

SaO2, %; SO2, %

-2 -1 0 1 2 3

Breathing, AU

10 15 20 25 30 35 40

1200 1250 1300 1350 1400

time, s

[tHb]; [O2Hb]; [HHb], mcM/L

-2 -1 0 1 2 3

Breathing, AU

10 15 20 25 30 35 40 45

1600 1650 1700 1750 1800

time, s

[tHb]; [O2Hb]; [HHb], mcM/L

-4 -2 0 2 4 6 8

Breathing, AU

60 65 70 75 80 85 90 95 100

1600 1650 1700 1750 1800

time, s

SaO2, %; SO2, %

-6 -4 -2 0 2 4 6

Breathing, AU

tHb tHb

Breathing

Breathing O2Hb

HHb HHb

SO2

SaO2

SO2

SaO2

O2Hb

Control subject OSA subject

a)

b)

c)

d)

Changes in brain hemodynamics and tissue oxygenation during sleep

(a,b) control subject, (c,d) OSA subject

Arterial blood oxygen saturation (SaO2 ) is measured via pulse oximetry.

Breathing is monitored via a strain gauge around the chest.

Brain tissue oxygenation (SO2) and tissue hemoglobin oxygen saturation are measured by NIRS

(31)

Right Frontal Lobe: Oxy-Hb (Red) Deoxy-Hb (Blue) Left Frontal Lobe: Oxy-Hb (Light Blue)

Deoxy-Hb (Green) Breathing (Black)

Pulse (Gray)

Breath holding

Time (sec)

Sleep Apnea

Time (sec)

sufferer OSA

Control Hemodynamic responses to hypoxia

(32)

Characterization of the subjects based on changes in [O₂Hb] and [HHb] due to breathing during sleep

1 - severe OSA subjects;

2 - youngest OSA subjects (29 & 44 years old) 3 - snorer with a family history of OSA ; 4 - oldest snorer (73 years old);

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 10 20 30 40

Time period during breath holding, s

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 10 20 30 40

D[O2Hb]

D[HHb]

Respiratory signal, AU D[HHb]

D[O2Hb]

Control non-snorer

OSA subject Breath holding

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20 40 60

Time period during daytime napping, s

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20 40 60

D[O2Hb]

D[HHb]

Control non-snorer

OSA subject Durnal nap

Diurnal napping Breath hold ing

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 10 20 30 40

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 10 20 30 40

D[O2Hb]

D[HHb]

D[O2Hb]

Control non-snorer

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20 40 60

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20 40 60

D[O2Hb]

D[HHb]

Control non-snorer

Diurnal napping Breath hold ing

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 10 20 30 40

Time period during breath holding, s D[O2Hb], D[HHb],mmol/L

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 10 20 30 40

D[O2Hb]

D[HHb]

D[O2Hb]

Control non-snorer

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20 40 60

D[O2Hb], D[HHb],mmol/L -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20 40 60

Time period during daytime napping, s D[O2Hb], D[HHb],mmol/L

D[O2Hb]

D[HHb]

Control non-snorer

Diurnal napping Breath holding

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 10 20 30 40

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 10 20 30 40

D[O2Hb]

D[HHb]

D[O2Hb]

Control non-snorer

-2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20 40 60

D[O2Hb], D[HHb],mmol/L -2.0 -1.0 0.0 1.0 2.0 3.0 4.0 5.0

0 20 40 60

Time period during daytime napping, s D[O2Hb], D[HHb],mmol/L

D[O2Hb]

D[HHb]

Control non-snorer

Diurnal napping Breath holding

Probability of opposite phase changes in [O2Hb]

and [HHb] due to respiration sleep, %

0 20 40 60 80 100

Right hemisphere

Left hemisphere

Non-snorers Snorers OSA subjects 1

3

4

2

We track the intra-hemispheric temporal correlations to observe anti-correlation or anti-phase behavior with respect to the changes in oxy- and deoxy-Hb, which is

displayed as an angle of 180 degrees.

(33)

Phase LeftPhase RightPhase Ox% R+L

Phase LeftPhase RightPhase Ox% R+L Phase LeftPhase RightPhase Ox% R+L

Phase LeftPhase RightPhase Ox% R+L

Healthy Control: six hours of sleep in histogram [column 1]

OSAS: three hours of sleep with multiple apneic events [column 2, red box]

CPAP: three hours of sleep in OSAS subject with CPAP [column 3, red box]

(Split PSG study: OSAS subject is diagnosed and fitted with CPAP for apneic event reduction therapy.)

Analysis Schemes:

The Hilbert Transform provides two types of temporal information: (1) we can track the correlations in time and (2) we can analyze all the points in time as a histogram.

The figures show the histograms of the inter-hemispheric oxygenation (Ox%)

(34)

Conclusion



NIRS provides non-invasive, transcranial, real-time measurements of cerebral oxygenation and hemo- dynamics.



NIRS gives direct information on cerebrovascular autoregulation.



NIRS may provide a cost-effective screening for cerebrovascular morbidity in OSAS sufferers.



NIRS may be associated with the standard

overnight polysomnography to monitor brain

vascular responsiveness to hypoxia in OSAS.

(35)

Age correlated changes in cerebral hemodynamics assessed by near-infrared

spectroscopy

(36)

Changes in oxy- and deoxy-hemoglobin concentrations assessed in a control non-snorer during breath holding

-1.5 0.0 1.5 3.0

0 8 16 24

Breath holding duration, s D[O2Hb] and D[HHb], mmol/L

D[O2Hb]

D[HHb]

Analyzed changes in cerebral hemodynamic parameters

on the 12

^th

second of breath holding and mean changes

during the 8

^th

– 16

^th

seconds (shaded area).

(37)

-3.0 -2.0 -1.0 0.0 1.0 2.0 3.0 4.0

20 30 40 50 60

Age, years D[O2Hb],mmol/L

Pearson Correlation r=-0.43*; p=0.025

N=27

-2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0

20 30 40 50 60

Age, years D[HHb],mmol/L

Pearson Correlation r=0.49**; p=0.009

N=27

-3.0 0.0 3.0 6.0 9.0

20 30 40 50 60

Age, years

DSO2, %

Pearson Correlation r=-0.48*; p=0.011

N=27 -3.0

-2.0 -1.0 0.0 1.0 2.0 3.0

20 30 40 50 60

Age, years D[tHb],mmol/L

Pearson Correlation r=-0.27; p=0.167

N=27

Decreases in

D

[O

₂

Hb],

D

[tHb], and

D

SO

₂

, and an increase in

D

[HHb] during hypoxic episodes were observed in older subjects.

(38)

NIRS in Attention Deficit Hyperactivity Disorder (ADD/ADHD)

Collaborative Project

University of Illinois at Urbana-Champaign Laboratory for Fluorescence Dynamics

Carle Clinic, Urbana Illinois

UIUC College of Medicine, Department of Pediatrics

The University of Texas

Southwestern Medical Center at Dallas

Department of Pediatrics

(39)

ADHD - Attention Deficit Hyperactivity Disorder

The most common psychiatric developmental disorder in USA

Qualitative Diagnosis

• Hyperactive type: “always on the go”

• Inattentive type: “struggle to stay focus”

• Mixed type: the most common

• Symptoms must be constant and across settings

Hypoperfusion hypothesis

• abnormal distribution of regional Cerebral Blood Flow (rCBF)

• frontal lobes, frontal-striatal-cerebellar circuits

• volumetric evaluation: PET, MRI, CT

Methylphenidate

• stimulates the release/block of reuptake of extracellular dopamine in the synaptic cleft.

• reduces inattentive, impulsive, and hyperactive symptoms.

(40)

0 5 10 15 C_ABS_DIF

0 5 10 15 20

A_NO_ABS_DIF

Absolute Oxygenation Difference (%)

Control

ADHD without medication

0 5 10 15 20

A_NO_ABS_DIF

0 5 10 15 20

A_M_ABS_DIF ADHD without medication

ADHD with medication

Absolute Oxygenation Difference (%)

Potential Diagnostic Screening

(41)

7 years old control child

Tapping exercise, Right hand.

-0.015 -0.01 -0.005 0 0.005 0.01 0.015

0 50 100 150 200 250 300 350

0 1

-0.015 -0.01 -0.005 0 0.005 0.01 0.015

0 50 100 150 200 250 300 350

0 1

D [H bO2] , D [H Hb] , m m ol/ L

Right Forehead

Left Forehead

Time (360 s), Tapping Periods (20 s)

(42)

7 years old ADHD hyperactive child Tapping exercise, Right hand. Showing

regional hypoperfusion?

-0.015 -0.01 -0.005 0 0.005 0.01 0.015

0 50 100 150 200 250 300 350

0 1

D detrended HbO2 A D detrended HHb A mark 5 per. Mov. Avg. ( D detrended HbO2 A) 5 per. Mov. Avg. (D detrended HHb A)

-0.015 -0.01 -0.005 0 0.005 0.01 0.015

0 50 100 150 200 250 300 350

0 1

D detrended HbO2 B D detrended HHb A mark 5 per. Mov. Avg. (D detrended HHb A) 5 per. Mov. Avg. (D detrended HbO2 B)

Right Forehead

Left Forehead

D [H bO2] , D [H Hb] , m m ol/ L

Time (360 s), Tapping Periods (20 s)

(43)

Final Remarks

• NIRS provides non-invasive, transcranial, real-time

measurements of cerebral oxygenation and hemodynamics.

• NIRS can measure absolute values of the concentrations of [HbO2], [HHb], and [tHb] and tissue oxygenation.

• NIRS aims to study specific hemodynamic patterns in ADHD:

• detect hypoperfusion with functional NIRS.

• detect brain development anomaly in populations of young children.

• assess brain segregation in the frontal lobes in ADHD.

• contribute to ADHD diagnosis and pharmacological treatment.

• More synchronous locations for measurements are needed.

(44)

Motor cortex activation

Collaborative project

University of Illinois at Urbana-Champaign Laboratory for Fluorescence Dynamics

Tufts University, Medford MA

Department of Electrical Engineering and computer Science

(45)

Plots of Source-Detector Pairs by DPF

-0.4 0 0.4 0.8 1.2

-10 0 10 20 30

time (s)

µmol/l

-0.4 0 0.4 0.8 1.2

-10 0 10 20 30

time (s)

µmol/l

-0.4 0 0.4 0.8 1.2

-10 0 10 20 30

time (s)

µmol/l

-0.4 0 0.4 0.8 1.2

-10 0 10 20 30

time (s)

µmol/l

-0.4 0 0.4 0.8 1.2

-10 0 10 20 30

time (s)

µmol/l -0.4

0 0.4 0.8 1.2

-10 0 10 20 30

time (s)

µmol/l

-0.4 0 0.4 0.8 1.2

-10 0 10 20 30

time (s)

µmol/l

-0.4 0 0.4 0.8 1.2

-10 0 10 20 30

time (s)

µmol/l

-0.4 0 0.4 0.8 1.2

-10 0 10 20 30

time (s)

µmol/l

-0.4 0 0.4 0.8 1.2

-10 0 10 20 30

time (s)

µmol/l

O₂Hb

HHb stimulation

(46)

D [HHb] (mM)

-1.0 -0.5 0.0 0.5

6

7

8 1

2 3

4 B A

5

Motor cortex activation

Data acquisition frequency = 1.25Hz

(47)

6

7

8 1

2 3

4 B A

5

D [HHb] (mM)

-1.0 -0.5 0.0 0.5

Motor cortex activation

Data acquisition frequency = 1.25Hz

(48)

Simultaneous

measurement of fMRI and NIRS of brain function

Collaborative Project

University of Illinois at Urbana-Champaign Laboratory for Fluorescence Dynamics

Beckman Institute

Carle Hospital Foundation, Urbana IL

(49)

Simultaneous Multi-source Frequency-domain NIRS and BOLD fMRI signals during motor functional

activation in humans: Collocation of signals

0 5 10 15 20 25 30

0.1 0.2 0.3 0.4

0 5 10 15 20 25 30-0.2

-0.1 0

0 5 10 15 20 25 30

0 0.1 0.2

D[OHb] (mM) 2 0.3

0 5 10 15 20 25 30-0.2

0

0.2 D[HHb] (mM)

0 5 10 15 20 25 30

0 0.5 1 1.5

0 5 10 15 20 25 30-2

-1 0 1

0 5 10 15 20 25 30

-0.1 0 0.1 0.2

0 5 10 15 20 25 30-0.5

0 0.5

Time (s) Subject A

Subject B

Subject C

Subject D

0 5 10 15 20 25 30

0 2 4

6 R

BOLD P

0 5 10 15 20 25 30

0 0.2 0.4 0.6

0 5 10 15 20 25 30

1 2 3

0 5 10 15 20 25 30

0.2 0.4 0.6 0.8 1

0 5 10 15 20 25 30

0 1

)P(% 2

0 5 10 15 20 25 30

0 0.2 0.4

0 5 10 15 20 25 30

0 1 2

0 5 10 15 20 25 30

-0.2 0 0.2 0.4

R(%)

time (s)

Subject A

Subject B

Subject C

Subject D

R: [HHb]

P: [tHb]

(50)

The Absorption and Scattering of Intensity Modulated NIR Light is Measured in the

Tissue Beneath the Sensor

Light detector position

Light source position Sample

source detector

(51)

Peripheral Vascular Disease

ISS Inc.

University of Illinois at Urbana-Champaign Laboratory for Fluorescence Dynamics

UIUC College of Medicine, VA Hospital, Danville, Illinois The University of Texas

Southwestern Medical Center at Dallas, Department of VA

Policlinico Monteluce, University of Perugia, Italy

(52)



Peripheral Vascular Disease (PVD) is a

chronic condition characterized by poor

circulation in the extremities

(53)



PVD manifests as insufficient tissue perfusion



Blocked blood flow can cause pain and numbness.

It can result in dangerously low delivery of

Nutrients and Oxygen to tissues especially in the foot and lower leg



Affects 12-14% of General Population and >20%

of people over 75



Over 100,000 Surgical Interventions Per Year



Early Detection, Monitoring, and Treatment May

Improve Quality of Life and Reduce Surgeries

(54)

The Human Clinical Trial for PVD Assessment

Patient Groups

Healthy Controls 17 Subjects

At Risk- 29 Subjects

Intermittent Claudication 27 Subjects

Rest Pain 7 Subjects

Dialysis 15 Subjects

Protocol

Oximeter Monitoring Of Both Calves Simultaneously Stand

Walk On Treadmill, 2 MPH at 3% Incline Stand

Pre And Post Exercise ABI (Ankle Brachial Index) Also Measured

(55)

Tissue Oxygenation at Rest (Average and Standard

Deviation)

63.0 67.6

72.0 69.9

50 55 60 65 70 75 80

Healthy Controls

At Risk Intermittent Claudication

Rest Pain

Saturation %

50.6 48.3

68.7

60.8

30 40 50 60 70 80

Rest Pain

Saturation (%)

Tissue Oxygenation during Exercise

(Average and Standard Deviation)

Conclusion: There is a correlation between saturation attained during exercise and clinical condition.

(56)

the step function in the shaded areas indicates exercise load (on a stationary bicycle)

patients affected by peripheral vascular disease show:

 larger desaturation during exercise

 longer recovery time after exercise

healthy subject

PVD patient (stage II)

exercise exercise

time (min)

Tissue hemoglobin oxygen saturation (%)

Typical hemoglobin saturation traces

20 30 40 50 60 70 80 90

0 2 4 6 8 10 12 14 16

(57)

14

49

175

202

-50 0 50 100 150 200 250

Rest Pain

Seconds

Post Exercise Saturation Recovery Time

(Average and Standard Deviation)

Conclusion: There is a strong correlation between saturation recovery time after exercise and clinical condition

(58)

Right Calf

Previous Right Side Femoral Artery Bypass

30 40 50 60 70 80 90

0 300 600 900 1200 1500

0

Stand Walk Stand

50 60 70 80 90 100 110 120

0 300 600 900 1200 1500

0

20 30 40 50 60 70 80 90 100

0 300 600 900 1200 1500

0

20 30 40 50 60 70 80

0 300 600 900 1200 1500

0

Hemodynamic Analysis Case Study

Saturation (%) THC (µM)

[Oxy-Hb] (µM) [Deoxy-Hb] (µM)

Left Calf

Scheduled For Left Side Femoral Artery Bypass Angiogram Verified Left Femoral Occlusion

(59)

Summary and Conclusions

Baseline Saturation, Exercise Induced De-Saturation, and Post Exercise Saturation Recovery Time all

Correlate with Clinical Condition

Exercise Induced Saturation measurements may be effective for PVD assessment

Hemodynamic Analysis of Oximetry Data may provide

Diagnostic Information in addition to PVD Assessment

(60)

ISS Imagent™

We are able to create functional maps of the tissue

(61)

Maps of O₂Hb during a venous occlusion of 3 minutes duration

cuff

subject with PVD, left leg

subject with mild PVD, right leg

normal subject, right leg

video runs 3 times faster than real time:

10s start of occlusion 70s end of occlusion

color scale in µM

(62)

Why Near-Infrared Spectroscopy and Imaging of Tissues?



Real-time monitoring of tissue oxygenation and hemodynamics



Non-invasive



Portable



Cost effective



Fast



Reliable

(63)

•University of Illinois at Urbana-Champaign

Laboratory for Fluorescence Dynamics Beckman Institute

•ISS Inc. Champaign, Illinois, U.S.A.

Grants R01 HD41342 R01 EB00559 R44 NS40597

•University of Illinois Medical Center at Chicago

Department of Neurosurgery

Center for Sleep and Ventilatory Disorders

•University of California, Irvine

Department Pediatrics

Developmental and Cell Biology Beckman Laser Institute

•The University of Texas Southwestern Medical Center at Dallas

Department of Pediatrics

Acknowledgements

•Carle Foundation Hospital, Urbana, Illinois

Department of Pediatrics Center for Sleep Disorders

•University of Kentucky

Sanders-Brown Center on Aging

(64)

Frequency Domain Near-Infrared Spectroscopy. Clinical Applications for the Study of the Oxygenation and Hemodynamics of the Brain and Muscle