Simultaneous optical coherence tomography imaging and beta ...

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OPTICS LETTERS / Vol. 28, No. 18 / September 15, 2003

Simultaneous optical coherence tomography imaging and beta particle detection Quing Zhu and Daqing Piao Department of Electrical and Computer Engineering, University of Connecticut, Storrs, Connecticut 06269

Mehran M. Sadeghi Department of Internal Medicine, Yale University School of Medicine, and Veterans Administration Connecticut Healthcare System, 950 Campbell Avenue, #111B, West Haven, Connecticut 06516

Albert J. Sinusas Department of Medicine and Diagnostic Radiology, Yale University School of Medicine Nuclear Cardiology, P.O. Box 208017, New Haven, Connecticut 06520-8017 Received March 26, 2003 A prototype hybrid catheter device designed for imaging and detection of vascular diseases is introduced. The prototype device integrates a high-resolution optical coherent tomography probe and a high-sensitivity beta detector into a single unit. With this prototype device we demonstrate the feasibility of simultaneous optical coherence tomography imaging and detection of beta particles. © 2003 Optical Society of America OCIS codes: 170.4500, 350.5610.

Coronary artery disease is a major cause of morbidity and mortality in the industrialized world. The major contributors to this morbidity and mortality are acute coronary syndromes (unstable angina and myocardial infarction) in which rupture or erosion of the f ibrous cap of a vulnerable atherosclerotic plaque leads to formation of a thrombus and occlusion of a blood vessel.1 Although it is of some help in def ining the anatomy of the plaque, intravascular ultrasound usually lacks the necessary resolution for fine def inition of plaque structure.2 Optical coherence tomography (OCT) can reveal intravascular structures to depths of several millimeters with unprecedented resolution of the order of 5 15 mm,3,4 an order of magnitude better than intravascular ultrasound. Recent studies have demonstrated that intravascular OCT can differentiate lipids from nonlipids and identify the intima from the lipid collection.5,6 OCT detects ref lected light and provides high-resolution imaging of intravascular structures; however, its functional imaging capability is limited. Recent research directed toward improving OCT functional imaging capabilities include use of polarization sensitive OCT,7 Doppler OCT,8 – 10 and contrast-enhanced OCT.11 Conventional approaches to imaging of atherosclerosis with single-photon emission computed tomography and positron emission tomography, although they are feasible, provide limited image resolution and (or) sensitivity that is inadequate to fully characterize targeted radio-labeled tracers. Therefore a number of investigators are developing intravascular radiation detection systems for early detection of atherosclerosis.11 – 14 Compared with external imaging, intravascular approaches have the significant advantage of detecting localized small lesions that might involve the intimae or the underlying media. For atherosclerosis imaging, even an ideal radio-labeled agent might deliver only ⬃0.01% of the administered dose to the target lesion,14 and these systems offer 0146-9592/03/181704-03$15.00/0

improved sensitivity for detection of small amounts of radioactivity with limited spatial resolution. Studies have shown that vulnerable plaques are metabolically active and can be detected at an early stage if the intima or the underlying media is directly interrogated with F-18 deoxyglucose by an intravascular detector that is sensitive to beta emission of the radionuclide F-18.11,14 The half-life of F-18 is relatively long (110 min) compared with those of other positron emission tracers, allowing time for clearance from the blood and localization in inf lammatory cells within the vascular lesion. Because the targeted cardiac vessels have diameters of less than 5 mm, they correspond well to tissue path lengths 共⬃3 mm兲 of beta particles with energies of .600 keV. However, catheter-based scintillating probes provide limited spatial resolution and can identify, at most, radiation activities of the size of catheter tips (a few millimeters). In this Letter we report a novel hybrid catheter-based prototype that integrates an OCT probe and a scintillating f iber for simultaneous high-resolution OCT structural imaging and highsensitivity detection of beta particles. It is our intention to use the current prototype not for clinical study but rather to demonstrate the feasibility of simultaneous OCT imaging and detection of beta particles. We believe that ref inements of our novel probe will open an exciting new research direction for high-resolution molecular imaging of vascular diseases. Our OCT system is conf igured based on a typical grating-based optical delay line, and the details have been published previously.10 Brief ly, a superluminescent diode with emitting wavelength centered at 1300 nm is used as the light source. The light beam from the source enters a 1 3 2 f iber coupler and splits into a reference for a differential detector input and a signal that is fed into a Michelson interferometer. The reference arm of the interferometer consists of a grating-based optical delay line. The depth © 2003 Optical Society of America

September 15, 2003 / Vol. 28, No. 18 / OPTICS LETTERS

(Z direction) scan is achieved when an achromatic lens converts the scanning of light in sectors by rotation of a mirror to parallel scanning upon a specially mounted diffraction grating. The sample arm of the interferometer is connected to a gradient-index lens. In the detection arm of OCT the output of the differential detector is bandpass filtered and digitized. A standard plastic scintillating f iber (Bicron Model BCF-12) of 1.5-m length and 0.5-mm outer diameter is used as a beta detector. A scintillating fiber is similar to a conventional optical fiber, except that it is doped with scintillating phosphors (1–2%) in the core. Ti-204 beta emitters were used for these studies because Ti-204 共b 2 兲 has spectra similar to those of F-18 共b 1 兲.14 Beta rays have a mean-free-path length of approximately 3 mm in tissue before they interact with low-atomic-weight plastic scintillating materials. The high-energy beta particles of .600 keV trapped by the scintillating fibers result in thousands of photons in the visible region (with a peak at 440 nm), which produce a short light pulse. In the experimental setup, 0.5-mm-diameter scintillating fibers are bundled together and protected by a black tubing as the cladding layer. One end of the fiber bundle is inserted through the wall of a black box, where a 1-mCi Ti-204 beta source is used to illuminate the scintillating fibers. The other end of the fiber bundle is connected to the detection window of a Hamamatsu R2949 photomultiplier tube (PMT). The PMT’s output is connected directly to the preamplifier unit of a TEL-USC20 universal computer spectrometer (Telatomic, Inc.) for multichannel pulse height analysis. The output pulses from the PMT are integrated by the spectrometer through a charge-sensitive amplif ier, amplif ied, and shaped with a linear amplif ier. These pulses are organized by a discriminator according to their height and are then converted from analog to digital. The signals are finally accumulated in memory and displayed on a screen. This system is able to output pulse height information and number of counts simultaneously. As the detection sensitivity depends strongly on the distance of the source to the scintillating fiber tip and on the number of scintillating fibers used, we evaluated the sensitivity (total counts) of the system by translating the source with a linear stage away from the scintillating fiber tips. A single scintillating fiber and groups of two, four, and six f ibers were used. The 6-mm f iber tips were exposed to the 1-mCi beta source. Figure 1 shows that sensitivity increases as the number of scintillating fibers is increased and decreases as the fiber-tip-to-source distance is increased. For the single f iber the poor sensitivity is related to the sensitivity of the scintillating fiber, the dark current of the PMT, and the amount of ambient light. One pair of trade-off parameters related to the hybrid catheter design is counting sensitivity and resolution. To provide higher spatial resolution for radiation detection, the length of scintillating fiber exposed to the radiation should be small. However, decreasing the scintillating fiber’s length will reduce the detection sensitivity. We evaluated this trade-off

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by exposing the 2-, 4-, and 6-mm scintillating fiber tips to the 1-mCi beta source and recording the total counts while laterally translating the source. Six scintillating f ibers were used for this test. Figure 2 shows the test results, which suggest that exposing a 6-mm fiber tip to radiation will reduce the resolution by half but will double the sensitivity compared with exposing a 2-mm fiber tip to radiation. In the f igure, 10 mm corresponds to the fixed position of a fiber tip. To demonstrate the feasibility of simultaneous OCT imaging and beta detection with coregistered position information, we constructed a prototype probe. A schematic diagram and a photograph of the prototype probe are shown in Figs. 3(a) and 3(b), respectively. In this prototype a GRIN lens of 2.5-mm outside diameter is placed inside a 3 mm 3 3 mm square glass tubing, and three 0.5-mm scintillating fibers are attached to the GRIN lens and positioned in a corner of the square tubing. The light from the GRIN lens is ref lected 90± by a tiny mirror attached to a rotational stage through a shaft. The shaft is also placed inside the 3 mm 3 3 mm square glass tubing. The two glass

Fig. 1. Radiation-detection sensitivity (total counts) versus distance between the source and the scintillating fiber tip.

Fig. 2. Radiation-detection sensitivity versus lateral position of beta source relative to the scintillating f ibers tips.

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OPTICS LETTERS / Vol. 28, No. 18 / September 15, 2003

corresponding to the cross section of OCT scanning. The depth of the OCT image is 2.53 mm. Using this setup, we acquired coregistered OCT and total radiation counts from freshly excised pieces of bovine coronary arteries. For convenience in the experiments the artery is shifted in 1-mm steps, and an OCT cross-section image and total radiation counts were acquired simultaneously at each step. The beta source was positioned close to a hole left at the artery and shifted together with the artery. The photon-counting result is shown in Fig. 4. When the beta source started to reach the scintillating fiber’s detection range, the total number of photon counts increased significantly, and when the source was away from the detection range the total number of counts was reduced to background level. The location of the point source beta emitter is marked by the large arrow in the f igure. Because of space limitations, only five OCT images, marked by the smaller arrows, are shown in the f igure. Fig. 3. Prototype probe for simultaneous OCT imaging and detection of beta particles: (a) schematic diagram, (b) photograph of the probe.

We acknowledge help with radiation measurements and the OCT imaging display from graduate student Yueli Chen. Q. Zhu’s e-mail address is zhu@ engr.uconn.edu. References

Fig. 4. Coregistered OCT images and total radiation counts acquired simultaneously from a fresh bovine coronary artery. The location of the beta emitter is marked by the large arrow. Five OCT images, marked by smaller arrows, are also shown.

tubes that hold the GRIN lens and the 90± ref lection mirror are aligned and separated by ⬃10 mm, in which space a scintillating fiber tip of 2-mm length is exposed to air to prevent attenuation of the beta radiation by the glass tubing. The rotation stage is driven by a dc motor through a timing belt–pulley assembly, and the speed of the rotation stage can be controlled. As the OCT A-line scanning speed is configured to be 64 Hz, 512 A-lines are obtained in one revolution of the 90± ref lection mirror, and the OCT signal is processed to have circumferential display

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