Biomedical%20Optics:%20Multichannel%20Spectroscopy

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Biomedical Optics Multichannel Spectroscopy

• Andrew Berger
• The Institute of Optics
• University of Rochester
• Quantum-Limited Imaging Detectors Symposium
• Rochester Institute of Technology
• March 2, 2009

3 biomedical spectroscopy arenas detectors
used daring to dream
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Biomedical Optics Application Areas

• diffuse photon propagation
• fluorescence lifetime spectroscopy
• Raman spectroscopy
• barely imaging!!!

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Breast imaging Computed Tomography
CT-scan (x-ray)
numerical reconstruction
scattering ltlt absorption ? paths straight lines
(courtesy F. Bevilacqua)
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Breast imaging Optical Computed Tomography
near-infrared light
sources
http//www.medphys.ucl.ac.uk/research/borg/index.h
tm
detectors
scattering gtgt absorption ? broad probability of
paths
(courtesy F. Bevilacqua)
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Area 1 Diffuse photon propagation
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Where biomedical optics lives.
DNA
biologicalwindow
courtesy V. Venugopalan, http//www.osa.org/meetin
gs/archives/2004/BIOMED/program/educ
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Important near-IR absorbers
19 M water
32 mM HbO2
11mM Hb
0.3 g/cm3 fat
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Near-infrared cerebral blood monitoring

• light in (690, 830 nm)

light out
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(No Transcript)
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Seeing functional responses visual stimulation
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Brain monitoring system layout
1-10 kHz modulationfor wavelength encoding
Analog Out DAQ Card
830 nm
Source 1
High Speed DAQ Card for demultiplexing
690 nm
830 nm
Avalanche photodiodes
Source 2
near
690 nm
near
far
far
far
far
far
far
Sample
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Typical detector for NIRS work

• Hamamatsu silicon avalanche photodiode modules
• Frequency rolloff in low MHz to GHz
• Spectral response out to 1000 nm

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Time-resolved measurements
pulse at t0
remitted light at t gt 0
r
absorption and scattering
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Hand-Held Optical Breast Scanner
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Hand-Held Optical Breast Scanner
Pham, TH., et al. Review of Scientific
Instruments, 71 , 1 14, (2000). Bevilacqua,
F., et al. Applied Optics, 39, 6498-6507,
(2000). Jakobowski et al., J. Biomed. Opt., 9(1),
230-238 (2004).
(courtesy F. Bevilacqua)
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Heavily multiplexed systems!
B. W. Pogueet al, Opt. Express 1, 391-403
(1997),http//www.opticsexpress.org/abstract.cfm?
URIOPEX-1-13-391
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http//www-nml.dartmouth.edu/nir/instrumentation.h
tml
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Diffuse propagation goals, requirements

• Distinguish benign from malignant tumor tissue
• Map blood activity (hemodynamics) within brain
• Sense deep within tissue (cm)
• Record at many locations
• Record at many wavelengths
• Time resolution to few psec

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Area 2 Fluorescence lifetime spectroscopy
Once again, psec-nsec timescale!
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Fluorescence lifetime spectroscopy
brain tissue
Butte et al., Diagnosis of meningioma by
time-resolved ?uorescence spectroscopy, Journal
of Biomedical Optics 10(6), 064026
(November/December 2005).
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Instrumentation for temporal fluorescence
Fang et al.
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Same idea, different group!
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Fluorescence lifetime goals, requirements

• Distinguish benign from malignant tumor tissue
• Record at many wavelengths
• Time resolution required to few psec
• Desirable to record at many locations (imaging)

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Area 3 Raman spectroscopy
incident photonwith energy E
molecule
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Raman spectroscopy
incident photonwith energy E
molecule gains energy DE
scattered photon has energy E -DE
todetector
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Raman spectrum of immune cell
aromatic amino acids
1340
RNA bases
1092
1259
720
phenylalanine
902
intensity (arb. units)
853
667
813
1580
1005
1651
1457
1127
1211
619
amide III
783
adenine
tyrosine
guanine
phenylalanine
C-H 2 def.
amide I
cytosine, uracil
C-N, C-C str.
Raman shift (cm-1)
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Detectors for Raman spectroscopy

• Thermoelectrically-cooledCCD array detectors
• Sensitive out to 1150 nm,limited by Si bandgap
• 25 micron square pixels
• typical dimensions, 256 x 1024 pixels

Princeton Instruments PIXIS CCD
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Raman spectroscopy goals, requirements

• Distinguish one cell type/state from another
• Quantify chemical levels in biofluids (e.g.
  blood)
• Yes, distinguish cancer from non-cancer
• Record at many wavelengths
• Long acquisition times (sec-minutes)
• Necessary to wavelength-tune down the
  fluorescence
• Desirable to time-gate away the fluorescence
  (intensified CCD or more exotic gating)

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Benefits of QLIDs for biomedical optics
psec temporalresolution
spectralresolution
spectralrange
thousandsof pixels
noise...
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Summary

• biomedical spectroscopy characterize tissue,
  biofluids, cells
• frequently in near-IR
• multiple factors driving sub-nsec time resolution
• many-many-channel sensing a game-changer
• get past the Si bandgap cutoff
• spectral resolution at each pixel good for
  diffuse spectroscopy

Questions?