Single pixel camera ophthalmoscope

Single pixel camera ophthalmoscope
Vol. 3, No. 10 / October 2016 / Optica
Single pixel camera ophthalmoscope
Laboratorio de Óptica, Universidad de Murcia, Campus de Espinardo (Edificio 34), Murcia 30100, Spain
Institut of New Imaging Technologies, Universitat Jaume I, Castellon 12071, Spain
*Corresponding author:
Received 27 May 2016; revised 22 August 2016; accepted 25 August 2016 (Doc. ID 267182); published 21 September 2016
Ophthalmoscopes to image the retina are widely used
diagnostic tools in ophthalmology and are vital for the early
detection of many eye diseases. Although there are various
effective optical implementations of ophthalmoscopes, new,
robust systems may have a future practical importance in cases
where ocular media present significant opacities. Here, we
present, as a proof of concept, a novel approach for imaging
the retina in real time using a single pixel detector combined
with spatially coded illumination. Examples of retinal images
in both artificial and real human eyes are presented for the
first time to our knowledge. © 2016 Optical Society of America
OCIS codes: (330.4460) Ophthalmic optics and devices; (330.7327)
Visual optics, ophthalmic instrumentation; (330.7328) Visual optics,
ophthalmic appliances; (110.0110) Imaging systems.
Modern flood-illuminated fundus cameras use a CCD or CMOS
camera with an array of thousands of pixels to obtain an image, or
video, of a part of the retina [1]. Good image quality is achieved
by illuminating the full area of interest homogenously. When
aberrations are corrected with the use of adaptive optics, even
detailed structures of the photoreceptor mosaic can be obtained
[2,3]. On the other hand, a scanning laser ophthalmoscope (SLO)
scans a light spot rapidly across the retina [4]. The reflected intensity of each traversed point is recorded using a spot detector
such as a photomultiplier tube (PMT) [5] or an avalanche photodiode (APD) [6]. Subsequently, a high-resolution image of the
retina is composed from the acquired data. Most recently, digital
light ophthalmoscopes were developed using a digital micromirror device (DMD) to scan lines across the retina, which are
imaged either on a line camera or on a two-dimensional (2D)
detector array to obtain an image [7,8]. All the former described
ophthalmoscopes are state-of-the-art devices and widely used as
medical instruments for monitoring the condition and alteration
of the eye fundus. Here, we introduce another imaging modality,
the single pixel camera technique, to the field of ophthalmic
imaging. The proposed system images the retina by combining
a spatially coded illumination with a single pixel detector in a
double-pass configuration. Single pixel imaging gained interest
within the last decade and has been successfully applied in biological
2334-2536/16/101056-04 Journal © 2016 Optical Society of America
imaging and microscopy [9,10], infrared imaging [11–13], ultrasonic imaging [14], terahertz imaging [15], and three-dimensional
(3D) imaging [16,17], and it has also been used in ghost imaging
[18–20]. This type of system avoids the need of a scanning unit,
which simplifies the optical system. The additional downscaling
to a single pixel detector, instead of a pixel array, might lead to
a lower illumination power, which benefits the patient’s comfort.
The system (Fig. 1) consists of a DMD (Vialux V7001, controller board V4395, chipset DLP 4100, pixel size: 13.68 μm,
resolution: 1024 × 768 px). Each mirror pixel on the DMD
can either guide light into the optical system or deflect it. The
DMD is illuminated homogenously with a broadband xenon
lamp (Hamamatsu L7810-02) with the UV part of the spectrum
blocked. This light source guarantees a stable output over time,
which is essential for discriminating minute intensity differences
coming from the spatial coding of the later-described pattern.
The illumination is spatially coded by multiple 2D binary
(black and white) patterns based on the Walsh–Hadamard transformation. These patterns are considered to have an optimum
weighted design for spatial coding. The number of black and
white pixels are equally distributed within each pattern and are
preferred to others, e.g., pseudo-random binary patterns [18,21].
The so-called Hadamard patterns or masks are generated with an
in-house developed software in C++ and sent to the DMD via a
USB 3.0 connection into the DMD’s onboard memory. It is essential to pre-load all patterns before displaying them, as this is the
only way to reach the maximum DMD frame rate of 22.727 kHz.
Subsequently, the patterns sequence is initialized within an area of
512 × 512 pixels in the center of the DMD. The masks are scaled
to match the size on the DMD, meaning e.g., for N 32, each
pixel of the pattern corresponds to 16 pixels on the DMD. Next,
the patterns are imaged through the lenses L1, L2, L3, L4, and the
eye’s optics onto the retina covering an area of around 15 deg of
the visual field. The light intensity reflected from the retina is
measured through the crystalline lenses, L5, L6, and L7 with a
silicon photomultiplier (SIPM, Excelitas Lynx A-33-050-T1A), the single pixel detector. This is synchronized with the
DMD, which triggers the intensity measurement of each projected pattern individually. The diaphragm D1 is placed centrally
on the back plane of lens L2, imaged via the telescope formed by
lenses L3 and L4 onto the pupil plane, and it therefore defines the
beams’ entry point. This configuration lowers the impact of
Vol. 3, No. 10 / October 2016 / Optica
Fig. 1. Schematics of the single-pixel ophthalmoscope. The patterns
generated on the DMD are imaged onto the retina. The diaphragm
D1 is conjugated to the pupil plane (red line) and defines the entry point.
F1 and F2 are interchangeable ND and bandpass filters.
aberrations on the image of the pattern and minimizes the area of
possible backscattering and reflections. The data from the
photomultiplier is transferred via an analog-to-digital converter
(National Instruments PCIe-6361, sampling rate 2 MS∕s) to a
desktop PC (i5-4590, quad-core, 3.3 GHz, 8 GB RAM). The
high sampling rate of the analog-to-digital converter (ADC)
allows for 84 measurements per pattern. Not all data points
are used for further processing, since data from the start of each
pattern measurement is affected by minute mirror wiggling while
the mirrors settle. The data received for each pattern are averaged
and stored as intensity i per pattern. A full reconstruction of an
image with the resolution N needs the amount of N 2 patterns
to be displayed, meaning for N 32, n N 2 1024. Since
the mathematical description of the binary Hadamard pattern
consists of negative and positive ones −1; 1, and the DMD
is only able to display zeros and positive ones 0; 1, there is
a need to display twice the number of patterns, resulting in n 2048 (equals 2 N 2 ) for N 32. The patterns are displayed in
the following order: a positive pattern (resembling patterns with 0
and 1) and, subsequently, its inverted complement (patterns
with −1 and 0). Afterward, the data from the inverted masks
are subtracted from the data of the positive masks, resulting in
the final data corresponding to the correct mathematical model
of the Hadamard patterns −1; 1. With this displaying order,
also used in other studies [9,10,22], noise is almost completely
eliminated and the data complements the optimal reconstruction.
One might argue that displaying only the positive patterns and
subsequently subtracting the average of all intensity measurements
would resemble the Hadamard patterns adequately, and, therefore,
be sufficient to reconstruct the object, but that only works satisfactorily under optimum illumination conditions. In a low-light environment, noise induced by the photomultiplier, the light source, or
the environment (Status LED, PC display) may have a severe
impact on the image reconstruction [23]. The reconstruction of
the object is done by the use of the following equation:
intensity i × patterni m; n;
imagem; n i
where patterni m; n denotes the set of matrices of the Hadamard
basis with dimensions N × N , consisting of “1 s” and “−1 s.”
The intensity i represents the averaged intensity per pattern after the
subtraction of the negative data from the positive data, and m; n
are discrete spatial coordinates. Note that the values of intensity are
the coefficients of the transformation of the image into the Walsh–
Hadamard basis, and Eq. (1) just transforms back to the spatial
domain. Figure 2 shows the obtained intensity measurements using
a model eye with a lens f eye 20 mm, ∅12.7 mm, and an imprinted letter acting as a retinal surrogate after imaging with a resolution of N 32 and a total of 2048 patterns. Figure 2(a) shows
the original object with a black square the size of 5 mm × 5 mm and
printed letters with four different grayscale values on a white letter.
Figure 2(b) shows the image of the reconstructed object obtained
with the maximum DMD frame rate and up-sampled to 128 ×
128 pixels without interpolation for better viewing purposes. A detailed image reconstruction is already possible due to the object’s
simple structure. Figure 2(c) displays the raw intensities, measured
84 times for each of the 2048 patterns. At this point, all the obtained
measurements are positive. The final data are shown in Fig. 2(d),
after the subtraction and averaging are done; consequently, the computed data contain negative values and vary around the zero baselines. Eventually, this set of data is used to reconstruct an image of
the object, as depicted in Fig. 2(b), by performing Eq. (1).
Figure 3 shows additional results using a model eye but imaged
with various resolutions, proofing the feasibility of the presented
optical system. It is worth to mention that for N 256, only all
positive patterns (n N 2 65536; all patterns would result in
n 2 N 2 131072) are shown due to the restrictions of the
DMD’s memory, which cannot store more than 87380 binary
patterns. In this case, the displaying time only doubles rather than
quadrupling (compared to N 128, see Table 1), but the reconstructed images are of lower quality, since the noise effects are not
compensated effectively.
The images shown in Fig. 3 are reconstructed without any
applied image post-processing except for N 256, where contrast
stretching is applied since the dynamic range was very narrow. The
quality of the images could be further improved by lowering the
frame rate of the DMD. That might be suitable for measurements
with a static object, but during in vivo measurements, subtle eye
Fig. 2. Top row: (a) original object, black square size is 5 mm × 5 mm
(b) reconstruction for N 32. Imaging time 0.09 s. Bottom row:
(c) full intensity measurements for N 32; 84 measurements for each
of the 2048 patterns, and (d) processed data after subtraction and averaging, resulting in the final 1024 intensity values.
Vol. 3, No. 10 / October 2016 / Optica
Fig. 3. Results using a model eye (raw images without image postprocessing). Top row: single frames, bottom row: the average of 10
frames. The DMD is set to its maximum display rate. Note: For
N 256, only the positive patterns were displayed, hence the increased
noise and artifacts. Imaging time per frame is indicated.
movements would affect the image quality drastically, since the area
of illumination needs to be constant. Furthermore, increasing the
imaging time would be contrary to the ophthalmoscope’s desired
real-time operation capability. One pixel in an N 32 reconstruction equals around 0.18 mm. Consequently, doubling N results in halving the pixel size, meaning that when N 256, one
pixel equals 0.022 mm. The scale bar is indicated within Fig. 3.
We were able to record images and video streams with the
proposed optical instrument. Table 1 shows an overview of the
achieved frames per second (FPS) during the continuous acquiring and reconstruction of images when operating in real-time
mode. The mathematical calculations to reconstruct an image
are simple, but the frame rate drops fast with the increasing resolution not only because of the exponential growth of pattern’s
size to be displayed, but also due to the vast amount of data that
needs to be processed. Additionally, we compared our video rate
to those obtained by other groups using the same imaging technique outside the field of retinal imaging.
The following results are obtained in living human eyes while
using multiple frame rates of the DMD and the total amount of
n 2 N 2 patterns. Figure 4(a) presents an initial unprocessed
result taken in a young subject volunteer with an illumination
time of 0.54 s and a resolution of N 32. The images on
the right in Fig. 4 show the average of 10 frames using the same
settings as the left ones. Averaging was done without correcting
for possible eye movements between each frame. Image postprocessing is not applied, but the image is up-sampled to a size
Table 1. FPS at Maximum DMD Frame Rate for Different
n 2 N2
Imaging time (s)
Theoretical FPSb
Experimental FPSc
Other groups
32768 65536
1.442 2.884
0. 57 0.04
[10,11,14] 2.5 [11,12,14,15] 0.5 [22] —
The table shows the obtained FPS for various resolutions.
For N 256, only positive patterns are shown due to the restriction of the
DMD memory.
Theoretical FPS is solely based on the maximum frame rate of the DMD
without further data processing.
Obtained experimental FPS including the processing and computation of the
Fig. 4. Reconstructed images of the optical nerve head using N 32.
Imaging time per frame is 0.54 s. The left side shows one frame; the right side
is the average of ten frames. Toprow covers an area of around7.5and the bottom
row around 14.5 visual degrees. All images are up-sampled to a size of
128 × 128 pixels. The inset in image (b) displays the image in its original size.
of 128 × 128 pixels. The main blood vessels, which join at the
optical nerve head, can be distinguished clearly. Further details
are not visible due to the lack of resolution and the presence
of noise. Higher-resolution images obtained from the averaged
video frames (taken from Visualization 1 for N 64 and
Visualization 2 for N 128) are shown in Fig. 5.
Compared to the results shown in Fig. 4, more details of
the vessel map around the optical nerve head are visible. The
improvement is not as good as anticipated, which is due to the
increased amount of time it needs to display the full set of patterns, and therefore, eye motions influence the outcome severely.
If the subject moves, even subtlely, different areas of interest are
illuminated, and this results in useless reflection intensity measurements. Furthermore, with the increase of resolution comes
an increased level of noise. Images taken with a resolution of N 256 are not shown here due to the following reasons: the overall
quality is low, as the imaging time for one single frame is around
three seconds (at maximum speed) and, therefore, eye movements
have a drastic effect on the reconstructed result. Second, with the
current hardware, we are not able to project the inverted patterns,
which are necessary to compensate for noise effects. As Figs. 4 and
5 show, an increase in resolution does not necessarily improve
the image quality, but rather introduces high-frequency noise.
This is mainly when finely structured patterns are not projected
perfectly onto the retina (due to aberrations) and, therefore, introduce a light haze on the reconstructed image, as shown in
Fig. 6. Nevertheless, the extended imaging time combined with
a non-constant area of illumination, due to the locomotion of the
eye, is the most challenging issue. To reduce the influence of motion artifacts, it is necessary to keep the imaging time as short as
possible. For that reason, it is possible to remove masks from the
display sequence, since some masks do not provide significant information. The technique of displaying less patterns is known as
adaptive imaging or evolutionary compressive sensing [10,17]. To
Fig. 5. Reconstructed and averaged images of the optical nerve head
using a resolution of (a) N 64 (11 deg, 30 frames) and (b) N 128
(14.5 deg, 7 frames). Illumination times are 1.29 and 5.15 s per frame.
Images are contrast stretched and (a) is scaled to 128 × 128 pixels.
gain knowledge about the patterns that can be eliminated, a full
set of 2 N 2 masks needs to be displayed prior to classification.
Subsequently, the obtained intensity data are sorted by means of
highest responsivity and then loaded into the memory of the
DMD to provide instant availability.
Afterward, a threshold is chosen to separate the patterns into
useful and dispensable. From there, we are left with two options
to gain an advantage of the lower amount of patterns:
(i) Increasing the illumination time per pattern, T , hence gaining a longer integration time for the detector area but maintaining
the same overall illumination time, t, which is not desired.
(ii) Keeping the illumination time per pattern, T , constant, results in a lower imaging time per frame.
Figure 6 shows results of the latter adaptive imaging configuration for 100, 75, 50, 30, 25, and 10% of 2 N 2 patterns in
the model eye setup and a resolution of 128 × 128 pixels. As can
be seen, displaying less than 30% of the patterns is sufficient for a
good reconstruction of the object but highly dependent on the
object’s structure and its grade of detail. With fewer patterns
displayed, the haze (high-frequency noise) in the reconstructed
images disappears and the real-time video frame rate increases
significantly. The imaging times per frame are indicated within
the images. Another technique that is commonly used with a
single pixel detector and a reduced amount of patterns is compressive sensing (CS) [12,16,21,24,25]. As it is based on a timeconsuming statistical algorithm, we omit CS for the moment
as we put our focus on a real-time optical instrument.
In conclusion, we described a novel instrument, based in a
single-pixel detection, for imaging the fundus of an eye in vivo
within an area of almost 15 visual degrees. Images and videos
taken in a static artificial eye demonstrate its feasibility and
Fig. 6. Adaptive imaging results for N 128. The percentage of patterns, which are displayed, and their imaging time per frame are indicated.
The first row depicts a single frame, while the bottom row shows an average of 10 frames. The DMD was set to its maximum frame rate.
Vol. 3, No. 10 / October 2016 / Optica
capability, while imaging in vivo remains challenging mainly due
to unintentional eye movements during extended illumination
times. In terms of image quality and resolution, the obtained
results cannot compete with comparable ophthalmic imaging
instruments, since the main limitation is the maximum frame rate
of the DMD. Future technology improvements and customized
hardware might close that gap. In addition, one can expect that
this type of single-pixel ophthalmoscope could operate under a
larger range of eye conditions, such as increased ocular aberrations
or scatter [26], as in the case of cataract patients [27]. Other potential advantages would be to obtain retinal images in spectral
bands beyond the current camera technology limits.
Funding. European Research Council (ERC) (ERC-2013AdG-339228 (SEECAT)); Secretaría de Estado de Investigación,
Desarrollo e Innovación (SEIDI), Spain (FIS2013-41237-R,
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