program in the first chapter.
In the second chapter ALTEA-MICE (Mice intermittent Irradiation with Concur-
rent Electrophysiological monitoring) study is described: the experimental sessions
as well as the evidences in the electrophysiological responses of the mouse retina
have been described in detail. My role has been chiefly the experimental set up,
and I also collaborated on the data analysis. The main results of this investigations
have been published [1], [2].
In the third chapter the system of the rod outer segments in suspension and the
mechanism of the activation of the photoreceptors are described.
The fourth chapter deals with the radiation effects in the biological tissue, and
in the fifth chapter there is particular regard to the effects of radiation on samples
containing a suspension of rods extracted from bovine retinae.
The effects on the rod photoreceptor rhodopsin has been studied: measurements
have been performed irradiating with 12C ions the outer segments of the rods in
suspension. The amount of the isomeric transformations (bleaching) of the molecules
of chromophore into the photoreceptor gives the extent of the effects of radiation. I
collaborated to the experiment and carried out the following data analysis.
Finally, in the sixth chapter the process of the photo-isomerization of rhodopsin
is explained by a model: the process starts with the water radiolysis and the forma-
tion of hydroxyl radicals OH in order to achieve the lipid peroxidation, then there
is the subsequent emission of visible photons which are responsible for the photore-
ceptor bleaching. Since rhodopsin is surrounded by phospholipids, present in high
concentration in the disc membranes, the effect of chemiluminescence is proposed
to be the cause of the photo-transduction cascade and the light flash perception as
a consequence. In order to test this hypothesis, a series of experiments was aimed
at studying the effects of the hydroxyl radicals produced in an enzymatic way. The
main results of this work are illustrated in chapter six, and have been published
in [3].
Chapter 1
ALTEA: an investigation on heavy
ion effects on nervous system
1.1 Visual phosphenes in space
On the historic July 1969 Apollo 11 mission, astronauts in lunar orbit reported an
incidental finding of various starlike flashes, streaks and clouds in their visual field.
Actually, astronaut Edwin Aldrin was the first to report phosphenes, or light flashes
(LF), in eyes during the space flight [4]. Subsequently, more detailed observation
were made on Apollo mission 12-17 and on Skylab 4 flights; during the Apollo-
Soyuz test project (ASTP) and on board Mir. Presently, on board International
Space Station (ISS) orbiting in the Low Earth Orbit (LEO), crew members perceive
LF. Although it is clear that the phosphenes are related to high-energy particles in
the space radiation environment, many details about LF origins are still unknown.
The flashes get perceivable usually under dark adaptation conditions. The flashes
are usually colorless; only in few cases they are colored. Because of these features,
the flashes are commonly accepted to be due mostly to scotopic vision. The different
shapes, as reported in some graphic descriptions in [5], are commonly illustrated as
stars, double stars, ’supernovas’, streaks, ’sky of stars’, clouds, bright flashes with
halo, and so on, observed, on Apollo, Skylab, and on Mir Station. Apparently
they differ from the diffuse glow from X-ray exposure or induced from neutron
generators [6]. Early human studies in accelerators [7] also suggest a correlation with
1
1.1. Visual phosphenes in space 2
increased particle flux in the eye. On Skylab 4 two dedicated light flash observing
sessions were conducted by one of the crewmen during the mission (on January and
on February 1974) [8], [9]. The phosphenes were seen only during crew sleep periods
at times when the crewmen were awake in their darkened sleep compartments.
On Mir [12], it is much lower (Sileye-1, 0.18 ± 0.02LF/min; Sileye-2, 0.13 ±
0.01LF/min) than on Apollo [13] (0.23±0.01LF/min), Skylab [14] (1.3±0.1LF/min)
and ASTP [15] (0.46±0.05LF/min). Frequency occurrence of LF is up to 25 times
higher near the magnetic poles than in equatorial latitudes. In general, the sug-
gested explanation for LF was in terms of interaction between cosmic ray particles
and the eye.
Reference [16] is a study initiated to collect information from people who have
recently flown in space. It is a survey conducted by anonymous questionnaire and
was performed among astronauts regarding their experience of sudden LF in space.
In all, 98 surveys were distributed to current NASA and ESA astronauts. Among
the 59 respondents, 47 noticed them sometime during space flight. Most often they
were noted before sleep, and several people even thought the LF disturbed their
sleep. There is an increase of occurrence with orbital altitude and inclination, as
one would expect from the increased particle fluxes there. The LF predominantly
appear white, but other colors are mentioned, pale green, blue and in particular
yellow (10%); they have elongated shapes, and most interestingly, often come with
a sense of motion. The motion is described as sideways or in-out, but never in the
vertical direction.
Interest in the flashes has arisen from the practical and fundamental significance
of the phenomenon. The practical aspect embraces the radiation safety, in-flight
rest, and capacity for work of astronauts in long-term and distant space flights.
Long travels outside the shielding magnetosphere are also being considered, with
the Moon and Mars as next plausible targets. Health risks due to microgravity and
cosmic radiation should nevertheless be expected to increase.
Almost all manned flights took and take place in LEO, at altitudes varying
between 200 and 500 km, with the only exception of the Apollo program, which
took man on the Moon and outside Earth’s geomagnetic shielding. Most LEO
June 22, 2009
1.2. The ALTEA program 3
missions (such as Mir, ISS and Shuttle) have a low inclination (51.6◦ with respect
terrestrial axis) to avoid high latitude areas, where the lower geomagnetic cutoff
results in a higher cosmic ray flux [17]. Cosmic rays and radiation measurements
inside spacecraft have been the subject of intense investigations throughout the
course of space exploration. These studies are particularly difficult since they need
to take into account the orbit dependence of cosmic ray flux and its propagation
inside the varying absorber thicknesses of the spacecraft.
The biophysics of particle action and the visual structures/functions eventu-
ally involved in the generation of phosphenes remained undefined. The aims of
the SilEye-1, SilEye-2, Alteino experiments were to investigate this phenomenon:
they are the precursors of the ALTEA experiments. SilEye-1 and SilEye-2 experi-
ments [18] performed LF observations on board Mir space station in the years 1995-
1999; a total of 18 hours of observation in 19 sessions resulted in the observation of
145 LF. SilEye-2 consists of a silicon detector telescope coupled to a ’helmet’ with
an eye mask, worn by the astronauts to carry out LF observations [10]. ISS data
have been taken in 2002 with Alteino device [19] during the Soyuz-34 flight. Alteino
was composed of two distinct devices: the cosmic ray advanced silicon telescope and
an ElectroEncephaloGrapher (EEG). Alteino project helped set the experimental
baseline for the ALTEA experiments, while providing novel information on the radi-
ation environment onboard ISS and on the brain electrophysiology of the astronauts
during orbital flights [20] [21].
1.2 The ALTEA program
ALTEA is a multidisciplinary project (including sub-projects such us ALTEA-MICE
experiments, ALTEA-biophys) carried on with international collaborations. The
project has been financed by the Italian Space Agency (ASI) with the collabora-
tion of the National Institute for Nuclear Physics (INFN) and rated ’Highly recom-
mended’ by the European Space Agency (ESA).
The ALTEA facility is available to the international scientific community for
human electrophysiological experiments, studies on particle flux, and dosimetry in
June 22, 2009
1.2. The ALTEA program 4
the ISS; the ALTEA hardware has been operating in the ISS - USLab since August
2006. It improves the particle observation capabilities of its precursors SilEye and
Alteino detectors while performing an advanced electrophysiological monitoring of
the Central Nervous System (CNS) during long orbital flights.
The ALTEA space particle detector is a natural development of previous SilEye
and Alteino detectors, with a much larger solid angle coverage for the particles
passing through the head. To obtain objective information about the LF perception
we included in the system the possibility of recording electrophysiological signals via
a high definition EEG. To monitor the status of the visual system in microgravity a
visual stimulator was also added. Correlations between electrophisiological changes
and passages of particles through the brain and/or retina in the space-adapted
conditions have been studied.
The detector system consists of an helmet shaped mechanical structure holding
6 advanced silicon telescopes to monitor incoming comic rays, an EEG to monitor
brain activity and a visual stimulator, to determine the functional status of the visual
system and study its dynamics. The silicon particle telescopes will be positioned
over the whole cerebral cortex. Each telescope is made of six silicon planes, and each
plane contains two contiguous basic sensor; the basic sensor is obtained assembling
back to back two chips with ion implanted resistive strips, 8×8 cm2 of sensitive area,
380µm thick, strip pitch of 2.4mm. To allow both x and y coordinate measurement
the strips of the two detectors are perpendicular.
The EEG system will measure the concurrent changes in the cortical bioelec-
trical activity; it is made up of a 32 electrode EEG cap including three floating
electrodes for retinogram measurements, and high resolution electronics allow for
electrophysiological readings. The visual stimulator, used to deliver standard stim-
uli, will permit to perform suitable stimulation routines, to determine the status of
the visual system. A three-button pushbutton is used to signal the LF perception.
At the highest sensitivity, the silicon detector system is able to detect particles from
He to relativistic Mo, and protons between 25 and 200MeV [22]. All information
will be stored together via an integrated data handling system that will also allow
transmission of the data to ground [23].
June 22, 2009
1.3. The ALTEA facility on board International Space Station 5
The ALTEA program includes ground-based experiments which are a series of
experiments based on measurements in particle accelerators. In the following sec-
tions 1.5 and 1.4 ALTEA-MICE and ALTEA-biophys are explained in detail.
1.3 The ALTEA facility on board International
Space Station
Figure 1.1: 8 March 2007. Astronaut Sunita Williams, Expeditions 14 and 15 Flight
Engineer, receives assistance from Astronaut Michael Lopez-Alegria, Expedition 14
Commander, in donning the sensor studded cap as she prepares to calibrate equip-
ment for the Anomalous Long Term Effects in Astronauts’ Central Nervous System
experiment in the Destiny laboratory module, image NASA ISS014E16195.
ALTEA space is mounted on an express rack in the USLab and can be utilized in
two modalities: dosimetry (DOSI) and central nervous system monitoring (CNSM)
[9].
In the DOSI unmanned modality, the six detectors on the helmet (silicon de-
tector system, SDS), continuously measure the environmental radiation. Data are
June 22, 2009
1.3. The ALTEA facility on board International Space Station 6
Figure 1.2: 8 March 2007. Astronaut Sunita Williams, Expeditions 14 and 15
Flight Engineer, wears the Anomalous Long Term Effects in Astronauts’ Central
Nervous System experiment helmet while conducting the experiment in the Destiny
laboratory module, image NASA ISS014E16208.
downlinked in real time to the ground, to the User Home Base in the Department of
Physics of the University of Rome Tor Vergata. Real time and off line software pro-
vides tools to discriminate the kinds of particles, calculate trajectories and energy
of the particles, constructing spectra of the measured radiation. ALTEA operated
in DOSI mode almost continuously from August 2006 to July 2007.
The manned experimental modality (CNSM) is specifically aimed at the study of
the interaction between particle passages and brain electrophysiological dynamics.
The detector is extended normal to the rack. The astronaut wears the EEG cap (see
figure 1.1), inserts the disposable pregelled electrodes, slides into the SDS helmet
and wears the visual stimulator which also permits dark adaptation. In this con-
June 22, 2009
1.3. The ALTEA facility on board International Space Station 7
Figure 1.3: A spectrum of the radiation environment into the USLab of the ISS.
From [9].
figuration, the SDS measures the particles passing through the astronauts head(see
figure 1.2). For about 25min he/she is presented with a standard set of visual
stimuli, then the astronaut relaxes; after about 5 − 10min of dark adaptation the
observing session starts: each perception of a LF is signaled with the pushbutton.
The observing session lasts about one hour. Total measurement time is about 1.5h:
one orbit. Seven sessions with three astronauts have been performed. The last one
was lengthened to allow a measurement with a full passage in the SAA (the other
six did not pass over the SAA during the observing time).
In the figure1.3 a measured spectrum of the radiation environment into the US-
Lab is shown. The spectum contains only fast particles, which releases an almost
constant energy (that is that the difference in released energy between the two outer
planes of the silicon telescope is < 10%). The plotted data refer to about six months
acquisition with 10 MIP threshold, where MIP means Minimum Ionizing Particle
1MIP = 109 keV/380µm of silicon.
June 22, 2009
1.4. ALTEA-biophys rationale and experiments 8
1.4 ALTEA-biophys rationale and experiments
The ALTEA-biophys section of the ALTEA program is a set of ground-based ex-
periments direct, in particular, to search for answers to the question: what are the
specific (or one of the possible) interactions causing the functional effects of the LF?
As explained in section 2.1, rhodopsin is at the start of the phototransduction
cascade in the process of vision. It is one of the best molecular transducers for con-
verting a visible photon into an electric signal. It is therefore the first candidate as
the target for the radiationvisual system interaction. For this purpose we started in
vitro investigations of the behavior of rhodopsin when hit by heavy ions. We have
been working to study the possibility that rhodopsin can also be activated by irradi-
ation with 12C nuclei. Intact rod outer segments (ROS) containing rhodopsin were
isolated from bovine retina. Suspended ROS were irradiated with 12C (200MeV/n,
well below the Cherenkov threshold, see section 3.2) at GSI. Spectrophotometric
measurements investigated the activation (bleaching) of the rhodopsin. With these
measurements we were able to show that radiation can induce bleaching.
1.5 ALTEA-MICE rationale and experiments
We set up an animal model using mice, irradiated with very short bursts of heavy
ions while concurrently acquiring electrophysiological data from the retina and from
the cortex. MICE is the acronym for Mice intermittent Irradiation with Concurrent
Electrophysiological monitoring.
ALTEA-MICE investigates the effects of heavy ions on the visual system of both
normal mice and mice with gene defects affecting retinal sensors. The experimental
main goal is to develop an animal model to better understand human risk related
to particle exposure. The experiments are expected to provide background informa-
tion that will supplement the ALTEA project on astronauts’ safety. ALTEA-MICE
also helps identify reliable laboratory conditions comparable in important respects
to those of astronauts in space and suitable for further investigations. Experiments
have been performed at the Brookhaven National Laboratories (BNL - Upton, NY,
USA), with NASA support, and at the Gesellschaft fur Schwerionenforschung mbH
June 22, 2009
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