Near-Infrared Spectroscopy of the Bladder: New Parameters for Noninvasive Evaluation of Detrusor Function

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1 Near-Infrared Spectroscopy of the Bladder: New Parameters for Noninvasive Evaluation of Detrusor Function April 2013, Vancouver Babak Shadgan MD, MSc, PhD Postdoctoral Fellow Bladder Care Center Department of Urologic Sciences University of British Columbia Light( When(light(is(transmi6ed(into(a(9ssue:(! light intensity, spectrum, wavelength, emission I 0########################################################################################### ###################################################### ## I 2###### # # # ###L # # #############c,##α# # # # # # # # # ####I 1# Tissue properties! absorption coefficient of the tissue! scattering coefficient of the tissue! reflectance coefficient of the tissue Tissue variables! tissue mass / consistency / volume! tissue structure (Micro-anatomy)! tissue biochemical composition! tissue biomechanical properties! tissue chromophore concentrations There is a logarithmic dependence and consistency between the tissue coefficients and variables, that defines the behavior of the tissue against light transmission. 2( 1(

2 Light( When(light(is(transmi6ed(into(a(9ssue:(! light intensity, spectrum, wavelength, emission I 0########################################################################################### ###################################################### ## I 2###### # # # ###L # # #############c,##α# # # # # # # # # ####I 1# Tissue properties! absorption coefficient of the tissue! scattering coefficient of the tissue! reflectance coefficient of the tissue Tissue variables! tissue mass / consistency / volume! tissue structure (Micro-anatomy)! tissue biochemical composition! tissue biomechanical properties! tissue chromophore concentrations There is a logarithmic dependence and consistency between the tissue coefficients and variables, that defines the behavior of the tissue against light transmission. Optical Diagnostics! Raman Spectroscopy! Optical Coherence Tomography! Laser Speckle Imaging! Near infrared Spectroscopy 3( Light( Raman(Spectroscopy(! light intensity, spectrum, wavelength, emission Tissue properties! absorption coefficient of the tissue! scattering coefficient of the tissue! reflectance coefficient of the tissue Tissue variables! tissue mass / consistency / volume! tissue structure (Micro-anatomy)! tissue biochemical composition! tissue biomechanical properties! tissue Chromophore concentrations Draga RO, et al. In vivo bladder cancer diagnosis by high-volume Raman spectroscopy. Anal Chem Jul 15;82(14): ( 2(

3 Light( Op9cal(Coherence(Tomography(! light intensity, spectrum, wavelength, emission Tissue properties! absorption coefficient of the tissue! scattering coefficient of the tissue! reflectance coefficient of the tissue Tissue variables! tissue mass / consistency / volume! tissue structure (Micro-anatomy)! tissue biochemical composition! tissue biomechanical properties! tissue chromophore concentrations Ren H, et al. Enhancing detection of bladder carcinoma in situ by 3-dimensional optical coherence tomography. J Urol Oct;184(4): ( Light(! light intensity, spectrum, wavelength, emission Tissue properties! absorption coefficient of the tissue! scattering coefficient of the tissue! reflectance coefficient of the tissue Tissue variables! tissue mass / consistency / volume! tissue structure (Micro-anatomy)! tissue biochemical composition! tissue biomechanical properties! tissue chromophore concentrations Shadgan B, Reid WD, Harris L, Power S, Jafari S, O Brien PJ. Monitoring of tourniquet induced skeletal muscle injury by near-infrared spectroscopy during orthopedic trauma surgery. J Biomed Optics, 2012, in press. 6( 3(

4 Principles( NIRS is an optical technique:! utilizes light in the NIR spectrum ( nm),! non-invasive,! to detect changes in tissue chromosphere concentrations,! to monitor tissue oxygenation, hemodynamics (metabolism) & function,! real time. 2 main physics principles underlie NIRS: light in the NIR spectrum, penetrates skin and scatters in tissue, Absorption properties of each chromophore is different at specific wavelengths in the NIR region. 7( Principles( NIRS is an optical technique - Chromophores! O 2 Hb / HHb Oxygenation! thb (O 2 Hb + HHb) Hemodynamics! Cyt CO Mitochondrial function! Water Hydration Under- Experiment! Glucose! Lactic acid 8( 4(

5 Principles( NIRS is an optical technique - Chromophores! O 2 Hb / HHb Oxygenation! thb (O 2 Hb + HHb) Hemodynamics! Cyt CO Mitochondrial function! Water Hydration Under- Experiment! Glucose! Lactic acid Spatially-resolved Configuration NIRS: measures Tissue Oxygen Saturation (%) 9( NIRS(in(Clinical(SeLngs( Clinical applications: Brain oxygenation monitoring Limb Hemodynamics monitoring Graft / tissue viability monitoring Muscle function monitoring Advantages:! Non-invasive! Real-time monitoring! Physiology, Metabolism, Function assessment! Confirmed validity, test-retest reliability! Not complex,, User friendly, simple to operate! Hand-held, Portable device, Not expensive technology! Not interfering with clinical instruments ( Physiologic(/(Pathologic( Condi9on( "( Alter Hemodynamics Oxygenation ( Metabolism ) " Dysfunction NIRS Limitations:! Complex basic photonic physics! Assumptions necessary for clinical use! Monitors changes in chromophore concentrations from initial baseline! Depth of penetration is limited to max 3-4 cm! Sensitive signals / motion artifacts 10( 5(

6 Dr.(Lynn(Stothers((/(Dr.(Andrew(Macnab((((((((((((UBC(( First NIRS Bladder Data * Macnab AJ, Stothers L. Development of a near-infrared spectroscopy instrument for applications in urology. Can J Urol Oct;15(5): ( 1 st (Study( (Rabbit s(bladder(nirs(monitoring(*( Animal model study: Objectives: to confirm the consistency and reproducibility of bladder monitoring with measurements made directly on the bladder surface comparing transcutaneous measurements, Devise: a 2-channel CW NIRS instrument Conclusion: Transcutaneous and direct NIRS measurements from bladder are comparable in pattern. Stothers A., Macnab J., Shadgan B, Detection of hypoxia within the detrusor using near infrared spectroscopy, J Urol (4): ( 6(

7 1 st (Study( (Rabbit s(bladder(nirs(monitoring(*( Animal model study: Objectives: to confirm the consistency and reproducibility of bladder monitoring with measurements made directly on the bladder surface comparing transcutaneous measurements, to investigate the effect of sequential episodes of general hypoxia on detrusor oxygenation. Devise: a 2-channel CW NIRS instrument Conclusion: Transcutaneous and direct NIRS measurements from bladder are comparable in pattern. NIRS provide some information re bladder oxygenation & hemodynamics. Stothers A., Macnab J., Shadgan B, Detection of hypoxia within the detrusor using near infrared spectroscopy, J Urol (4): ( 2 nd ((Study( (Pilot(study(of(bladder(NIRS(in(an(adult(*( Asymptomatic adult: Objective: Feasibility of bladder NIRS monitoring during voiding Device: 4 channels CW laser-powered NIRS Conclusions: NIRS is a feasible method for transcutaneous monitoring of bladder oxygenation and hemodynamics during voiding. Stothers L, Shadgan B, Macnab A. Functional near-infrared spectroscopy (fnirs) ; dynamic topography of the human bladder during voiding. JBO. 2009;14(2): ( 7(

8 3 rd (Study( (NIRS(pa6ern(of((voiding((adult)( Asymptomatic adult Bladder voiding pattern An initial small rise in thb / O 2 Hb A gradual increase in thb / O 2 Hb A gradual decrease in thb / O 2 Hb after Uroflow completed Minimal changes in HHb Device: LED powered-nirs in spatially resolved configuration. Detrusor Is a unique smooth muscle that contrary to other muscles can increase its perfusion during the contraction.* Greenland JE, Brading AF. The effect of bladder outflow obstruction on detrusor blood flow changes during the voiding cycle in conscious pigs. J Urol. 2001;165(1): ( 4 th (Study( (NIRS(pa6ern(of(natural(filling((adult)( Asymptomatic adult: Objective: to evaluate the feasibility of using a miniature wireless NIRS device for bladder monitoring. * to investigate the normal pattern of bladder filling. Device: LED powered-nirs in spatially resolved configuration. Shadgan B, Reid WD, Gharakhanlou R, et al., Wireless near-infrared spectroscopy of skeletal muscle oxygenation and hemodynamics during exercise and ischemia. Spectroscopy. 2009;23(5): ( 8(

9 4 th (Study( (NIRS(pa6ern(of(natural(filling((adult)( Asymptomatic adult: Conclusions: NIRS can detect a consistent pattern of natural bladder filling and emptying in asymptomatic adult. Pattern of natural filling: Macnab A.J., Stothers L., Shadgan B., Wireless near infrared spectroscopy (NIRS) of the bladder detrusor during uroflow in ambulant children and adults. J Urol. 2009;181(4): ( 4 th (Study( (NIRS(pa6ern(of(natural(filling((adult)( Asymptomatic adult Bladder filling pattern Our observation supported by previous reports* confirming: Negative linear relationship between detrusor pressure and perfusion in the noncompliant cycle of bladder filling. Bladder vasodilation as extends during filling, (extension of coil shaped vessels) Brading AF, Greenland JE, Mills IW, McMurray G, Symes S. Blood supply to the bladder during filling. Scand J Urol Nephrol Suppl. 1999;201: Andersson P O, et al., Changes in vascular resistance in the feline urinary bladder in response to bladder filling. Br J Urol 1985; 134: ( 9(

10 5 th (Study( (NIRS(monitoring(of(bladder(dysfunc9on((adults)"*( Symptomatic adult: Objective: to assess and compare the pattern of bladder NIRS during voiding in healthy & subjects with LUTS. Device: LED powered-nirs in spatially resolved configuration Shadgan B, Afshar K, Stothers L, Macnab A. Near-infrared spectroscopy of the bladder: a new technique for studying lower urinary tract function in health and disease. SPIE. 2010;7548:75480U; doi: / ( 5 th (Study( (NIRS(monitoring(of(bladder(dysfunc9on((adults)( Symptomatic adult: Observations: Detrusor blood flow impairment (thb) Hypoxic detrusor during voiding Loss of initial increase in thb/o 2 Hb upon permission to void in some cases Shadgan B, Afshar K, Stothers L, Macnab A. Near-infrared spectroscopy of the bladder: a new technique for studying lower urinary tract function in health and disease. SPIE. 2010;7548:75480U; doi: / ( 10(

11 5 th (Study( (NIRS(monitoring(of(bladder(dysfunc9on((adults)( Symptomatic adult: Conclusions: NIRS show different patterns of changes in detrusor oxygenation & hemodynamics in asymptomatic vs. symptomatic adults during voiding. 21( 6 th (Study( (NIRS(monitoring(of(bladder(dysfunc9on((adults)( Symptomatic adult - Overactive Bladder Subjects: 43 adult diagnosed as OAB Method: UDS NIRS filling NIRS voiding Results: UDS vs. NIRS Voiding: P < 0.02 UDS vs. NIRS Filling: P < Conclusion: NIRS is a potential, noninvasive, diagnostic tool for DO in patients with OAB symptoms.** ** Farag FF, et al., Near-infrared spectroscopy: a novel, noninvasive, diagnostic method for detrusor overactivity in patients with overactive bladder symptoms--a preliminary and experimental study. Eur Urol. 2011;59(5): Our observations support previous reports* # Doppler ultrasound studies have revealed significant variations in oxygen supply and consumption of the bladder wall during involuntary muscle contraction. Greenland(JE,(et(al.(J(Urol(1996;156: ( Kershen(RT,(et(al.((J(Urol(2002;168:121 5.( Azadzoi(KM,(et(al.(J(Urol(1996;155: ( 22( 11(

12 7 th (Study( (NIRS(monitoring(of(pelvic(floor(muscles(*( Transvaginal NIRS Monitoring Objectives: To investigate the feasibility of transvaginal NIRS monitoring of female pelvic floor muscles during voiding and exercise. Device: A custom-made transvaginal NIRS probe connected to a CW 2- chanell NIRS. Conclusion: Transvaginal NIRS can monitor bladder and pelvic floor muscle function. Shadgan B, Stothers L, Macnab A. A Transvaginal probe for near infrared spectroscopic monitoring of the bladder detrusor muscle and urethral sphincter. Spectroscopy. 2008;22(6): ( 8 th (Study( (NIRS(evalua9on(of(PFM(func9on(*( NIRS evaluation of PFM function following a PFN exercise program Objectives: To investigate the effect of a 4-month pelvic floor exercise program on pelvic floor muscles function monitored by NIRS in female with urinary incontinence. Conclusion: NIRS optical monitoring of pelvic floor muscles shows a significant improvement in PFM function after a 4-month PFM exercise protocol. NIRS can be used as an optical biofeedback system for PFM exercise. Stothers L, Marques A, Shadgan B, Macnab A. Near infrared spectroscopy of pelvic floor muscles shows the effect of pelvic floor muscle training in women with stress incontinence. J Urol. 2011;185:4S(871) 24( 12(

13 9 th( (Study( (NIRS(monitoring(of(bladder(func9on((Children) *( Asymptomatic children: Objective: to examine the practicality of NIRS bladder monitoring in children to investigate the pattern of bladder NIRS monitoring in asymptomatic children during voiding, to compare this pattern with asymptomatic adult s pattern. Device: LED powered-nirs in spatially resolved configuration Asymptomatic 10 yr. Girl Afshar K., Shadgan B., Macnab A., Stothers L., Near Infra Red Spectroscopy: A Non-Invasive Method to Evaluate the Function of the Lower Urinary Tract in Children, APA 2009: ( 9 th( Study( (NIRS(monitoring(of(bladder(func9on((Children)( Asymptomatic children: Objective: to investigate the normal pattern of bladder voiding, and to compare it with adult s pattern. Device: LED powered-nirs in spatially resolved configuration Conclusions: NIRS can detect a constant pattern of voiding in children. This pattern is similar to adult s pattern. 26( 13(

14 9 th( Study( (NIRS(monitoring(of(bladder(func9on((Children)( Asymptomatic Adult vs. Children Adult Children 27( 10 th( Study( (NIRS(monitoring(of(bladder(dysfunc9on((Children)( Symptomatic NLUTD Children: Objective: to investigate the pattern of bladder NIRS during voiding in NLUTD children Device: LED powered-nirs in spatially resolved configuration Frequent UTI - Frequency / 7 yr. Girl Afshar K., Shadgan B., Stothers L., Macnab A., Near infrared spectroscopy and altered detrusor oxygen consumption in non-neurogenic lower urinary tract dysfunction in children. J Urol. 2010;183:4S(629). 28( 14(

15 10 th( Study( (NIRS(monitoring(of(bladder(dysfunc9on((Children)( Symptomatic NLUTD Children Reproducibility 29( 10 th( Study( (NIRS(monitoring(of(bladder(dysfunc9on((Children)( Symptomatic vs. Asymptomatic Patterns Frequent UTI Frequency 7 yr. Female 30( 15(

16 10 th( Study( (NIRS(monitoring(of(bladder(dysfunc9on((Children)( Symptomatic NLUTD Children Hypoxic Pattern Recurrent UTI, Incontinence, Nocturia / 4 yr. Male 31( 10 th( Study( (NIRS(monitoring(of(bladder(dysfunc9on((Children)( Symptomatic NLUTD children Fatigued Detrusor Similarity of the pattern of detrusor muscle deoxygenation during voiding in dysfunction subjects and the pattern of skeletal muscle deoxygenation at the fatigue point *, suggests that a degree of muscle fatigue is likely behind the dysfunctional bladders. Shadgan B, et al. Sternocleidomastoid muscle oxygenation and hemodynamic response to incremental inspiratory threshold loadeng measured by near infrared spectroscopy. J Resp PhysiolNeurobiology, 2011;178(2): ( 16(

17 10 th( Study( (NIRS(monitoring(of(bladder(dysfunc9on((Children)( Symptomatic NLUTD Children: Conclusions: Pilot data suggests children with NLUTD have impaired bladder oxygenation/hemodynamics during voiding. NIRS data can add more information on detrusor physiology - even before voiding starts - which has potential diagnostic relevance. Macnab AJ, Shadgan B, Stothers L, Afshar K. Ambulant monitoring of bladder oxygenation and hemodynamics using wireless near-infrared spectroscopy. Can Urol Assoc J Jan 24:1-7 33( Neurogenic(Bladder(Dysfunc9on( 34( 17(

18 11 th (Study(%(Neurogenic(Bladder(Dysfunc9on *( Neurogenic bladder in adults with spinal cord injury Objectives: The feasibility of NIRS as a non-invasive method for monitoring detrusor oxygenation and hemodynamics in SCI patients, The patterns of change in detrusor chromophore concentrations during the filling and emptying phases of simultaneous invasive UDS testing, The correlations between the changes in detrusor NIRS and UDS measures. Shadgan B, Macnab A, Nigro M, Stothers L. Monitoring of lower urinary tract function in patients with spinal cord injury using near infrared spectroscopy. Proc. SPIE 8207, (2012). 35( 11 th (Study(%(Neurogenic(Bladder(Dysfunc9on( Subjects! 20 adult paraplegic men and women (aged years)! with neurogenic bladder dysfunction! referred to UBC Hospital for regular UDS Method:! Preparation & UDS catheterization! NIRS placement (Wireless NIRS - spatially resolved configuration)! Bladder 40 ml/s rate! UDS & NIRS Data collection Marked Points: urgency and urinary leakage Analysis:! Correlation analysis for associations between UDS & NIRS data! Paired t-test to examine deference of TSI% before and during leak. 36( 18(

19 11 th (Study(%(Neurogenic(Bladder(Dysfunc9on( Results: Bladder filling:! Comparable patterns of change in O 2 Hb, HHb & thb were evident during bladder filling in all subjects: an initial gradual increase in detrusor O 2 Hb, thb with minimal changes in HHb followed by a gradual decrease in O 2 Hb, thb and TSI% at the terminal phase of bladder filling. 37( 11 th (Study(%(Neurogenic(Bladder(Dysfunc9on( Results: Urinary leakage:! leakage: 12 mean bladder volume of ± ml (range: ml) mean detrusor pressure of 62.9 ± 24.3 cm H 2 O (range: cm H 2 O)! Significant fall in detrusor O 2 Hb & thb, seconds before episodes of strong urgency and urinary leakage! Detrusor TSI% were significantly fell during each episode of urinary leakage (Mean ΔTSI%: -3.9±2.1, P<0.005).! 38( 19(

20 11 th (Study(%(Neurogenic(Bladder(Dysfunc9on( Results: NIRS vs. UDS measures:! Strong consistency between changes in detrusor thb & TSI% and changes in detrusor pressure during filling across the subjects. (P<0.01) 39( 11 th (Study(%(Neurogenic(Bladder(Dysfunc9on( Neurogenic bladder in adults with spinal cord injury Conclusions: NIRS monitoring of bladder function is feasible and can provide new physiologic information related to voiding dysfunction in individuals with neurogenic bladder noninvasively. Detrusor TSI% was observed to fluctuate during filling in neurogenic individuals providing observation of possible neurovascular alterations in these cases. Noninvasive Evaluation Invasive Current Standard 40( 20(

21 Bladder(NIRS(Monitoring( Overall(Conclusions( $ Bladder NIRS data analysis may help to recognize and differentiate the dysfunctional conditions noninvasively: Pattern of changes in NIRS measures Trend of changes Magnitude of changes $ Bladder NIRS monitoring may be a useful screening method for early detection of bladder malfunction. $ Bladder NIRS may be a useful noninvasive method for monitoring the effect of medications. $ Ischemia impairs detrusor contractility and function. $ Detrusor ischemia is associated with leakage and voiding mechanism. 41( Noninvasive(Measurement(of(Pdet.(,(a(desire!( Urodynamics is an invasive method with some inherent limitations. How to quantify detrusor pressure in a noninvasive way?! 42( 21(

22 Noninvasive(Measurement(of(Pdet.(,(a(desire!( Urodynamics is an invasive method with some inherent limitations. How to quantify detrusor pressure in a noninvasive way?! NIRS study: It is all about trend analysis of Δ-chromophore concentration, We filter motion signals in order to better investigate the trend of changes. 43( Noninvasive(Measurement(of(Pdet.(,(a(desire!( Sports medicine: Diagnosis of CECS Ultrasound: Pulsed Phase-locked Loop Ultrasound Wiemann et al., JOT, 2008: Detecting intracompartmental pressure 44( 22(

23 11 th (Study( (NIRS(Detrusor(Pulsa9on(Signal(Analysis( A novel Approach Detrusor Pulsation Analysis Noninvasive Diagnosis of Detrusor high pressure Noninvasive Quantifying of Detrusor Pressure 45( 11 th (Study( (NIRS(Detrusor(Pulsa9on(Signal(Analysis( A novel Approach Detrusor Pulsation Analysis Noninvasive Diagnosis of Detrusor high pressure Noninvasive Quantifying of Detrusor Pressure 46( 23(

24 (Acknowledgement:( ( (Dr.(Lynn(Stothers( ( (Dr.(Andrew(Macnab( ( (Dr.(Koroush(Afshar( ( (Dr.(Mark(Nigro( Rick(Hansen(Founda9on( Canadian(Ins9tute(of(Health( Canadian(Ins9tute(for(Photonic(Innova9ons( Michael(Smith(Founda9on(for(Health(Research( Interna9onal(Associa9on(of(Op9cs(&(Photonics((SPIE)( ( English Bay, Vancouver, Canada 48( 24(

25 4 th (Study( (NIRS(monitoring(of(bladder(dysfunc9on((adults)( Symptomatic adult - Bladder Outlet Obstruction Observation: Hypoxic Detrusor (not ischemic) 49( 4 th (Study( (NIRS(monitoring(of(bladder(dysfunc9on((adults)(*( Symptomatic adult - Bladder Outlet Obstruction Progressive functional impairment bladder due to BOO is associated with changes in detrusor hemodynamics. Increased Pdet in BOO is associated with detrusor Classification and regression tree algorithm based on noninvasive NIRS data have comparable discriminant ability for diagnosing and classifying males with lower urinary tract symptoms as either obstructed or unobstructed. Specificity: 88% Precision: 94% Stothers L, Guevara R, Macnab A., Classification of male lower urinary tract symptoms using mathematical modelling and a regression tree algorithm of noninvasive near-infrared spectroscopy parameters. Eur Urol. 2010;57(2): ( 25(