A fiber-based ratiometric optical cardiac mapping channel using a diffraction grating and split detector

Abstract

Optical fiber-based mapping systems are used to record the cardiac action potential (AP) throughout the myocardium. The optical AP contains a contraction-induced motion artifact (MA), which makes it difficult to accurately measure the action potential duration (APD). MA is removed by preventing contraction with electrical-mechanical uncoupling drugs, such as 2,3-butanedione monoxime (BDM). We designed a novel fiber-based ratiometric optical channel using a blue light emitting diode, a diffraction grating, and a split photodetector that can accurately measure the cardiac AP without the need for BDM. The channel was designed based on simulations using the optical design software ZEMAX. The channel has an electrical bandwidth of 150 Hz and an root mean-square dark noise of 742 muV. The channel successfully recorded the cardiac AP from the wall of five rabbit heart preparations without the use of BDM. After 20-point median filtering, the mean signal/noise ratio was 25.3 V/V. The APD measured from the base of a rabbit heart was 134 +/- 8.4 ms, compared to 137.6 +/- 3.3 ms from simultaneous microelectrode recordings. This difference was not statistically significant (p-value = 0.3). The quantity of MA removed was also measured using the motion ratio. The reduction in MA was significant (p-value = 0.0001). This fiber-based system is the first of its kind to enable optical APD measurements in the beating heart wall without the use of BDM.

FIGURE 1

Schematic diagram of the fiber-based ratiometric optical channel. The labels A–D refer to the illumination pathway of the channel as described in the text. All lenses have a radius of 5 mm. The dichroic mirror and filter are 25 mm × 25 mm × 1 mm. The diffraction grating is 25 mm × 25 mm × 9.5 mm. The labels E–I refer to the detection pathway of the channel as described in the text. The xyz directions are also shown. The y direction is perpendicular to the xz image plane.

FIGURE 2

Amplification circuit. The photodiode current (I) is converted to a voltage by the 100-MΩ resistor in stage 1 using an operational amplifier (OPA124U, Burr-Brown Corp.). In stage 2, the signal is amplified using an additional operational amplifier (OPA124U, Burr-Brown Corp.).

FIGURE 3

The relative power of di-8-ANEPPS dye (bold line), photodiode responsivity (plane line), and relative power multiplied by the photodiode responsivity with ZEMAX sample wavelengths (plane line with triangles). The spectra represented are not identical to di-4-ANEPPS, but differences are not expected to be significant.

FIGURE 4

(A) The fiber is butt-coupled to the royal blue LED. The LED is mounted on a heat sink and fan. (B) The constructed optical system. The lens is glued to the outer can of the photodiode, which is mounted to a micromanipulator. The letter labels refer to the block diagram in Fig. 1.

FIGURE 5

ZEMAX simulation at peak wavelength of 636 nm. Our design took into account spatial limitations due to the mounting of the optical parts. The letter labels refer to the optical block diagram in Fig. 1.

FIGURE 6

(A) ZEMAX simulation using 12 sample wavelengths. The central wavelength is 655 nm. (B) Zoom in of the yz image plane. (C) Image on the xy image plane with grid representing the photodiode surface. Units are in millimeters.

FIGURE 7

y displacement voltage changes on each detector. The green detector (squares) peaks 0.635 mm from the red detector (triangles). The red and green detectors peaked at −650 mV and −645 mV, respectively. This figure shows that the magnitude of the voltage decreases as the laser beam and aspheric lens used to focus the light onto the detector become misaligned.

FIGURE 8

x displacement as a function of z displacement (squares). The slope of the linear fit line is 0.0008. The inverse tangent of the slope results in the system at ∼0.05° off axis.

FIGURE 9

Bandwidth range of the amplification circuit. The maximum bandwidth was 4 kHz (asterisk). The minimum bandwidth was 110 Hz (squares). Both detectors were set to a cutoff bandwidth of 150 Hz (solid line).

FIGURE 10

Microelectrode and optical rabbit AP recordings. (A) Two raw recordings where the AP was not visible due to the MA. The red signal voltage (black line) decreases with depolarization, whereas the green signal voltage (gray line) increases with depolarization. (B) The ratio of the two raw signals. (C) The ratio of the two raw signals after median filtering and normalization. The signals were normalized by subtracting the minimum value then dividing the result by the maximum value minus the minimum value. (D) The force transducer shows the magnitudes of motion that coincide with the MA in the original signals. (E) The microelectrode recordings shown exhibit some artifact during the repolarization phase of the AP. This is due to the tissue-contraction motion causing the microelectrodes to pull out of the cell membrane.