SHAPE Society

1. University of Kentucky
Near-Infrared Spectroscopy:
Near To or Far From Our Expectations?
Steven R. Alford and Robert A. Lodder
Advanced Science and Technology Center
University of Kentucky
http://www.pharm.uky.edu/
Copyright 2002 University of Kentucky

2. University of Kentucky
Near-IR Spectrometry
Near-IR spectrometry uses the absorption,
emission, or scattering of light in the near-infrared
portion of the electromagnetic spectrum (700 -
3000 nm) by atoms or molecules to determine
sample composition or characteristics.
Editorial slides, VP Watch, February 27, 2002, Volume 2, Issue 8

3. University of Kentucky
Technology is available for spectrometric sensing at very long distances
Hyperspectral Imaging and Remote Sensing

4. University of Kentucky
Several techniques are being tested to identify vulnerable
plaques before they disrupt. Of these, near-IR and Raman
spectrometry seem most relevant to fiber-optic catheters.
In 1993 Cassis and Lodder described a near-IR imaging
system and parallel vector supercomputer used with a
fiber-optic probe to produce chemical maps of the intimal
surface of living arteries.
Editorial slides, VP Watch, February 27, 2002, Volume 2, Issue 8
Catheter-Based Photonic Technologies
for Detection of Vulnerable Plaque

5. University of Kentucky
Romer et al. have demonstrated detection of
atherosclerotic plaque using NIR Raman
spectroscopy. However, Raman spectroscopy,
while offering greater intrinsic spectral resolution,
is also more challenging in clinical applications.
Naghavi, Soller, and colleagues have used NIR
spectroscopy for measuring plaque activity and
inflammation parameters such as pH and lactate.
Editorial slides, VP Watch, February 27, 2002, Volume 2, Issue 8

6. University of Kentucky
Near-IR predictions of lipid pool, fibrous cap, and
macrophage infiltration have been made with good
sensitivity and specificity using fiber-optic probes.
P. Cherukuri, P. Riggs, I. Darrat, K. Dumstorf, and R. A. Lodder, Near-IR Spectrometry of Structural Components
of Susceptible Plaque In Vivo and In Vitro, CPS:analchem/0101001, (Jan) 2001, 1-13.
Detection of Lipid Pool, Thin Fibrous Cap, and Inflammatory Cells in Human Aortic Atherosclerotic Plaques by
Near-Infrared Spectroscopy; Pedro R. Moreno, Robert A. Lodder, K. Raman Purushothaman, William E. Charash,
William N. O’Connor, and James E. Muller ; Circulation 2002 105: 923 - 927; published online before print
February 4 2002, 10.1161/hc0802.104291.

7. University of Kentucky
Near-IR Spectrometry
Elastic photon scatter
Near-IR light penetrates water (and blood) well
Decent signal intensities from most organic compounds
Sample contact is not really required
Better S/N
Quantitative calibrations are linear
Conventional optics and fibers can be used
Lower intrinsic spectral resolution, more band overlap
Use collagen I to compare near-IR, IR and Raman spectra

8. University of Kentucky
Peaks are sharp at low energies, and broaden at high energies

9. University of Kentucky
Infrared (IR) Spectrometry
elastic photon scatter
Good intrinsic spectral resolution
Strong signal intensities from most organic compounds
Decent S/N
IR does not penetrate water (or blood) well
Special optics and fibers are required to handle light
Attenuated Total Reflectance requires good sample contact
Quantitative calibrations are not very linear

10. University of Kentucky
IR peaks of pure compounds are strong and rather well resolved

11. University of Kentucky
Good intrinsic spectral resolution
Raman spectrometry can be performed in regions where it
penetrates water well
Sample contact is not really required
NIR and Raman both give more linear calibrations than IR
Weak signal intensities from most organic compounds
Few photons undergo inelastic scatter, decreasing S/N
Technological advances in lasers, holographic notch filters,
and detectors make Raman spectroscopy possible.
In vitro Raman is a good tool for plaque chemistry
Raman Spectrometry
Inelastic photon scatter

12. University of Kentucky
Many sharp bands are seen in the Raman spectrum of a pure compound

13. University of Kentucky
Multivariate Calibration
Secondary analytical methods like Near-IR, IR, and Raman
spectrometry require calibration by primary methods.
HPLC, UV-visible spectrometry, capillary electrophoresis and
analytical ultracentrifugation are also calibrated by standards
(i.e., gravimetry or mass spectrometry serve as the primary
analytical methods)
Multivariate chemometric methods like PLS, PCA, BEST
are required to extract quantitative information from complex
samples like atherosclerotic plaques.

14. University of Kentucky
Spectra of pure collagen I and III standards were obtained in vitro through 1
mm of whole blood using a fiber optic probe. Identical integration times were
used. Multivariate principal component analysis was used to assess the ability of
near-IR, IR, and Raman spectrometry to differentiate between the collagen
samples.

15. University of Kentucky
Ten Replicate Spectra of Collagen I = O, Collagen III = +
NIR spectra separated well
Strong signals scattered back
Collagen I and III have
distinctive NIR spectra
IR spectra did not separate
Signals weaker than Near-IR
Signals scattered only from
blood
No light reached the collagens
Raman spectra separated
somewhat
signal level lowest
Nd:YAG light reached
sample, but noise was
high

16. University of Kentucky
NASA JPL
MULTIFUNCTIONAL ACTIVE-EXCITATION SPECTRAL ANALYZER (MAESA)
The NASA MAESA has a wavelength range from 0.5 to 2.5 micrometers. Selection rules make Near-
IR and Raman spectrometry complementary methods.
The MAESA includes a laser to illuminate a point or a line on a target. Other optics image the target
onto a rectangular focal plane array of InGaAs photodetectors. The light returning from the target is
long-wavelength-filtered to remove the laser wavelength component, then focused onto a convex
diffraction grating, which spectrally disperses the remaining Raman-scattered light along a row of the
array. Removing the grating enables Near-IR spectrometry with a tunable laser.
Hyperspectral Imaging can be Accomplished with
One Combined NIR and Raman Instrument
Diagram: NASA Photonics Tech Briefs Jan. 2002

17. University of Kentucky
New Technologies Remain to be Explored
Superconducting transition edge detectors
Quantum cascade lasers
B. Cabrera, R. M. Clarke, P. Colling, A. J. Miller, S. Nam, and R. W. Romani, Detection of
single infrared, optical, and ultraviolet photons using superconducting transition edge sensors,
APPLIED PHYSICS LETTERS 1998, 73(6), 735-737.
Claire Gmachl, Deborah L. Sivco, Raffaele Colombelli, Federico Capasso
& Alfred Y. Cho Ultra-broadband semiconductor laser, Nature 2002, 415, 883-887.
Typically, lasers emit light of one pure wavelength. Quantum cascade lasers generate a beam
containing wavelengths in a wide region of the electromagnetic spectrum. This new
broadband laser can be made to operate in the NIR/IR. The device contains hundreds of
extremely thin semiconductor layers, each one affecting the energies of electrons passing
through it. A high voltage forces an electric current to penetrate layer after layer in the stack.
The physical confinement of many of those stacked layers makes them act as quantum wells.
The TE optical detector is so sensitive that it can clock the arrival of a single photon of light
and still measure its energy. The detector works in the infrared, optical and ultraviolet portions
of the spectrum. An electrical current keeps the detector at its critical
transition temperature. The sensor is cooled slightly below the transition temperature and the
electrical current raises its temperature to the critical value. When the energy from an
individual photon reaches the superconductor, it heats up the electrons in the material. This
heating causes an increase in the resistance. The greater resistance causes a decrease in the
electrical heating that exactly equals the amount of energy that the photon deposited. This
keep the detector at the right temperature and also gives a precise measurement of the photon's
energy and arrival time.

18. University of Kentucky
Near To or Far From Our Expectations?
Insufficient man-hours and public and private research funding
have been directed into spectrometric technologies for detection of
vulnerable plaque.
Photonic technologies have tremendous untapped potential
that will continue to grow as new tools like MAESA, quantum
cascade lasers, and superconducting detectors become available.
Organizations like AEHA must continue to promote awareness
of the problem and the potential solutions so photonics can
fulfill our expectations.
http://www.pharm.uky.edu/