Key Technologies• Laser Spectroscopy

• White Light Spectrometry

• Glas Fibre Technology

• Optical Sensors (worldwide patents)

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Title

Determination of oxygenmetabolism in tissues by combinedwhite light spectrometry and laserspectroscopy – an overview aboutmethod and study results.

O2C (oxygen to see)• Laser- and White-light spectroscopy• contineuous monitoring of• blood flow (capillary microcirculation)• venular oxygen saturation (hypoxia)• capillar-venular filling with blood

(venous congestion)• 50 ms measurement time• depth selectiv (e.g. skin,

muscle, bone) 100 µm - 15 mm

• No imagesDisadvantages

Schematicpath ofphotons intissue

White lightWhite lightFlow

VelocityVelocity

020406080

500 540 580 620

I

λ

SO2

relHb

Changed in color and intensity

Tissue

Blood vessels

Changed in frequency (f2=f1+∆f )

Erythrocytes

Fibre probe

f1 f2

Laser-light Colored light

LightScattering onMitochondria

Tissue Spectroscopy and -SpectrometryLaser-light

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Tiss

ue p

O2

[mm

Hg]

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SO2

[%],

Blo

odvo

lum

e [%

]

Arteriole Capillaries Venule

11 % 16 % 73 %

exponential pO2 Gradients

linear Haemoglobin Saturation (SO2)

Lethal CornerLast meadow

3 % physically solved oxygen

1,8 %

1,5 %

1,2 %

Measurementarea pO2electrode

Measurementarea O2C

(oxygen to see)

Comparison: tcpO2 and O2C

The Impact of O2C for the Quantification of Tissue Ischemia inDiabetic Foot Ulcers (Diabetes Care, Vol. 27, Dec. 2004)

• Patient lying on his back• Start of measurement after 10 minutes rest• Definition of constant measurement t ime• Opsite®-Film between wound and probe• Same applicat ion pressure of the probe by fixat ion of theprobe with Opsite®-Film of constant size• No movement of the extremities during measurement

S. Beckert, A. Königsrainer, M. Witte, S. CoerperUniversitätsklinikum Tübingen, Klinik für Allgemeine Chirurgie

Fig. 2: Probe Application

“The O2C is a reliable and valid method, for theasscessment of tissue microperfusion.Measurements are easy to perform and not timeconsuming. Results are acccurate .. . detectclinical ly relevant ischemia earlier, predict thefuture healing process and choose appropriatetreatment schedule”

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SO2 rHb Flow Velocity

SO2

[%],

rHb

[AU

], Fl

ow[A

U],

Velo

city

[AU

]

70

50

70

150

35

50

2015

heal

er

heal

er

heal

er

heal

er

non-

heal

e r

non-

heal

er

n-h

n-h

diabetes patient, tcpO2 < 30 mmHg,

nonpalpable peripheral pulse, grad I ulcers,

measures at the wound site, significant at all parameters

Amputation level assessment using lightguidespectrophotometry

Prosthet Orthot Int 1995 Dec;19(3):139-47Amputation level assessment using lightguidespectrophotometry.Harrison DK, McCollum PT, Newton DJ, Hickman P,Jain AS

Investigation sheme on the lower leg,• 10 locations on a circle and

• 10 locations in a row

Critirea for ampuation due to insufficient woundhealing• Mean value smaller than 30% in SO2and• Lowest values below 10% SO2 more than 3 out of20 values.

The combination of these criteria gave asensitivity and selectivity of 1.0 for prediction ofa successful outcome of transtibial amputations.

Parameters of Microcirculation and Healing Time of BurnWounds

The groups marked by � are showing a significant reduction(p<0,05) of flow and velocity values compared to the othergroups. The haemoglobin concentration and oxygensaturation of the operated group were significant lower to thegroup with 2-3 weeks healing. Neither flow, velocity, Hbconcentration nor oxygen saturation were showingsignificant changes between the measurements on the firstand the third day after burn.

On 15 patient 86 burn wounds were examined. Thewounds were clinically evaluated and examined additionallywith the O2C (LEA Medizintechnik GmbH). Themeasurements were conducted within 24 hours and 3 daysafter the day of burn. The wounds were divided into 4groups (healing time 1-2 weeks, 2-3 weeks, >3 weeks andoperated wounds).

M.Pfau, K.Merz, H.O.Rennekampff,H.E.SchallerKlinik für Hand-, Plastische-, Rekonstruktive- undVerbrennungschirurgie der BG-Unfallklinik Tübingen an derEberhard-Karls-Universität Tübingen

Healing Time vs Flow(<24 h after burn)

1-2 Weeks operated0

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rela

tive

Flow

[Uni

ts]

�

�

2-3 Weeks > 3 Weeks

P2P1

7th day after burnClear healing tendency on P1, delayed healing on P2

“Retrospective analysis shows a correlation betweenhealing time and flow and velocity.

B. Brell, B. Temmesfeld-Wollbrück, et. Al. Department ofInternal Medicine/ Infection Diseases, University Medicine

Berlin, GermanyCrit. Care Med. 2005 Vol. 33, No.4 pp 819-826

Adrenomedullin reduces Staphylococcus aureus α-toxin-induced rat ileum microcirculatory damage

Meausures in mucosashow good correlationbetween perfusionpressure (SMA-Pressure)andmucosal oxygensaturation SO2(mHbO2) measured byO2C Measures on mucosa

show good correlatonbetween

• amout of hemoglobinrel.Hbcon

and• gain in weight of the

gut

-> (venous congestion,edema)

Increase microvascular permeability and perfusion mismatch arehallmarks of sepis and spetical shock

Oxygen Saturation of mucosa of stomach inhealthy persons (A) and patients with sepsis (B) taken from

(10) recorded by O2C(oxygen to see)

(10) Am J Respir Crit Care Med 1998 May;157(5 t 1):1586-92 Abnormalities of gastric mucosal oxygenation in septic shock: artial responsiveness to

dopexamine.Temmesfeld-Wollbruck B, Szalay A, Mayer K, Olschewski H, Seeger W, Grimminger F.

AGE-reiche Mahlzeit (HAGE): 15.100 kU AGEgebacken/gebraten - 220ºC, 20 Min

AGE-arme Mahlzeit (LAGE): 2750 kU AGEgekocht/gedünstet - 100ºC, 10 Min

Methoden:

Postprandiale Dysfunktion der Mikrozirkulation nach einer Mahlzeitreich an Advanced Glycation Endproducts (AGE) bei Patienten mitTyp 2 Diabetes mellitus - protektive Rolle von Benfotiamin

Postprandiale Veränderung der RH HAGE undLAGE

4,8

1,5

2,2

4,4

3,1

3,8

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ktiv

e H

yper

amie

(RH

) Quo

tient

des

Blu

tflus

ses

HAGELAGE

Postprandiale Veränderung der RH, HAGE und HAGWE-Benfo

3,4

1,4 1,4

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ktiv

e H

yper

oxie

(RH

) Quo

tient

des

Blu

tflus

ses

HAGEHAGE+Benfo

Stirban A., et. al.; Bad Oeynhausen,Poster, 40. Jahrestagung DDG, Berlin 5/2005

• Eine AGE-reiche, Mahlzeit führt zueinem signifikanten Abfall derGefäßfunktion der Mikrozirkulation(O2C oxygen to see), der mindestens 6Stunden anhält und ausgeprägter ist alsnach einer AGE-armen Mahlzeit• Benfotiamin kann diesen negativenEffekt reduzieren

MYOCARDIAL MICROCIRCULATION DURING ISCHEMICPRECONDITIONING IN OFF-PUMP BYPASS SURGERY

Tissue SO2 increased going from the first to the thirdocclusion from 75±11% to 83±8% (p<0.001). rHb as a markerof postcapillary venous haemoglobin concentration increasedsignificantly (77±8 vs. 85±6, p=0.002). Superficial and deepmyocardial blood flow decreased significantly (317±17 vs.308±36, p <0.001; 402±56 vs. 350±50, p < 0.001;respectively).

Methods: 21 patients (14 males) scheduled for OPCABwere enrolled in the study. Intraoperatively, the LAD wasoccluded for 2 min followed by a 2 min reperfusion interval.The procedure was repeated three times.

A. Lichtenberg, K. Knobloch, M. Pichlmaier,St. Ringes-Lichtenberg, H. Mertsching, U. Klima, A.HaverichThoracic and Cardiovascular SurgeryMedizinische Hochschule Hannover, Germany

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base

line

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ia2n

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hemia

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chem

ia

SO2[

%]

SO2

“Oxygen-to-see system is capable ofdetecting myocardial microcirculation invivo real time.

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90 100 110 120 130 140 150 160 170 180NADH fluorescence (aU)

Sinu

soid

al h

emog

lobi

n O

2 sat

urat

ion

(%)

y = 116.05 - 0.44 xr2 = 0.94p < 0.005

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Sinu

soid

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emog

lobi

n O

2 sat

urat

ion

(%)

y = 71.037 - 0.0729 xr2 = 0.867p < 0.001

Lethal hepatocyte injury (PI-labeled nuclei / 10-1 mm3)

C. Wunder, R. Brock, A. Krug, N. Roewer,O. EichelbrönnerAnesthesiology, University of Würzburg, GermanyDepartment of Pharmacology & Toxicology,University of Arkansas, USA

Conclusions

Remission spectroscopy (O2C)represents a simple and reliable methodfor hepatic sinosoidal SO2determination. Significant reduction in hepatic SO2during early stages of systemicinflammation in parallel an increasing NAD(P)Hautofluorescence (=inadequate oxygensupply)

in parallel an increasing marker of liver

A remission spectroscopy system for in vivo monitoring ofhemoglobin oxygen saturation in murine hepatic sinusoids, in early

systemic inflammation (Comparative Hepatology 2005, 4:1 doi:10.1186/1476-5926-4-1)

O2C (oxygen to see) Monitoringon mouth mucosa during

bypass surgery

•Stop of HLM (8 sec.)

•Bolus of NO

•Spreading of thorax

O2C Sonde an Mundmukosa, Teilausschnitt des Zeitverlaufs während NO-Bolusgabe

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17:19:03 17:20:42 17:22:22 17:24:01 17:25:41 17:27:23 17:29:03 17:30:43 Time [hh:mm:ss]

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O2C Sonde an Mundmukosa, Teilausschnitt des Zeitverlaufs während Maschinenstopp

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],

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dFlo

w [A

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Aorta

auf

, Mam

mar

ia a

nnae

hen

gekl

emm

t

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chin

e lä

uft w

iede

r

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chin

e st

eht

O2C Sonde an Mundmukosa, Teilausschnitt des Zeitverlaufs während Spreizung des Thorax

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6 :37 :1 26 :38 :5 36 :40 :3 26 :42 :1 26 :43 :5 26 :45 :3 16 :47 :1 26 :48 :5 26 :50 :3 26 :52 :1 26 :53 :5 26 :55 :3 26 :57 :1 26 :58 :5 47 :00 :3 27 :02 :1 37 :03 :5 37 :05 :3 47 :07 :1 37 :08 :5 37 :10 :3 37 :12 :1 37 :13 :5 37 :15 :3 27 :17 :1 47 :18 :5 4

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[%],

rHb

[AU]

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axs p

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O2C (oxygen to see) probe in rectum,Bad Oeynhausen,

Patient on HLM, Hypothermia 30 C

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[%],

rHb

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,

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w [A

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MarkSO2 P1SrHb P1SFlow P1S50 Per. Gleitender Durchschnitt (Flow P1S)50 Per. Gleitender Durchschnitt (SO2 P1S)50 Per. Gleitender Durchschnitt (rHb P1S)

an H

LM u

nd A

orta

zu

OP

End

e

Byp

ass

End

e

Aor

ta o

ffen

aufw

ärm

en

Her

z st

eht

Influence of haemorrhagicshock on fracture healingM. Bumann, T. Henke, H.Gerngross, L. Claes, P. Augat,Department of OrthopaedicResearch and Biomechanics, UniUlm, GermanyLangenbecks Arch Surg. 2003,Oct.,388(5):331-8.

Measurement at the level offracture (tibia), 1cmdistal/proximal and soft tissuewith O2C(oxygen to see)Shock group with volumeresuscitationControl group without

Shock group with volumesubstituion has no reduction inblood flow in the distal andsoft tissue regionsandshows a better fracture healingoutcome.

Flexural rigidity

shock group control group

shock group control group

4 x in fractured bones

3 x in fractured bones

Failure load

Tibia

Muscle

Skin

w/o

hai

r

Acral skin (no hair)

Skeletal muscle

Mouth mucosa

Stomach mucosa

Inte

stin

e muc

osa

Rect

al m

ucos

a

Brain

Myocard

Liver

KidneysSple

enSer

osa

Mus

cula

ris

Lungs

Monitoring of regional cirulatory system- on a functional basis

Bone

Probetypes- Flat probes for skin and muscle (e.g 2 and 8 mm depth)- Muscle probe 15 mm depth- Micro-probes 0.8 mm and 2.3 mm diameter- Redong probe for buried flapsand transplants (monitoring)

Thank you

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