Article

X-ray microbeams: Tumor therapy and central nervous system research

Department of Bio-system Engineering, Yamagata University, Yamagata, Japan
Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment (Impact Factor: 1.22). 09/2005; 548(1-2):30-37. DOI: 10.1016/j.nima.2005.03.062
Source: PubMed
ABSTRACT
Irradiation with parallel arrays of thin, planar slices of X-ray beams (microplanar beams, or microbeams) spares normal tissue, including the central nervous system (CNS), and preferentially damages tumors. The effects are mediated, at least in part, by the tissue's microvasculature that seems to effectively repair itself in normal tissue but fails to do so in tumors. Consequently, the therapeutic index of single-fraction unidirectional microbeam irradiations has been shown to be larger than that of single-fraction unidirectional unsegmented beams in treating the intracranial rat 9L gliosarcoma tumor model (9LGS) and the subcutaneous murine mammary carcinoma EMT-6. This paper presents results demonstrating that individual microbeams, or arrays of parallel ones, can also be used for targeted, selective cell ablation in the CNS, and also to induce demyelination. The results highlight the value of the method as a powerful tool for studying the CNS through selective cell ablation, besides its potential as a treatment modality in clinical oncology.

Full-text

Available from: Tetsuya Yuasa
Nuclear Instruments and Methods in Physics Research A 548 (2005) 3037
X-ray microbeams: Tumor therapy and
central nervous system research
F.A. Dilmanian
a,
,Y.Qu
b
, S. Liu
b
, C.D. Cool
c
, J. Gilbert
a
,
J.F. Hainfeld
d
, C.A. Kruse
c
, J. Laterra
e
, D. Lenihan
b
, M.M. Nawrocky
a
,
G. Pappas
a
, C.-I. Sze
c
, T. Yuasa
f
, N. Zhong
a
, Z. Zhong
g
, J.W. McDonald
b,h,1
a
Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA
b
Department of Neurology and the Spinal Cord Injury Restorative Treatment and Research Program, Washington University,
St. Louis, MO, USA
c
Department of Pathology, University of Colorado Health Sciences Center, Denver, CO, USA
d
Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA
e
The Kennedy Krieger Institute, John Hopkins School of Medicine, Baltimore, MD 21205, USA
f
Department of Bio-system Engineering, Yamagata University, Yamagata, Japan
g
National Synchrotron Light Source, Brookhaven National Laboratory, Upton, NY 11973, USA
h
Departments of Neurology, Neurological Surgery, Anatomy, and Neurobiology, and the Spinal Cord Injury Restorative
Treatment and Research Program, W.U
Available online 9 April 2005
Abstract
Irradiation with parallel arrays of thin, planar slices of X-ray beams (microplanar beams, or microbeams) spares
normal tissue, including the central nervous system (CNS), and preferentially damages tumors. The effects are
mediated, at least in part, by the tissue’s microvasculature that seems to effectively repair itself in normal tissue but fails
to do so in tumors. Consequently, the therapeutic index of single-fraction unidirectional microbeam irradiations has
been shown to be larger than that of single-fraction unidirectional unsegmented beams in treating the intracranial rat
9L gliosarcoma tumor model (9LGS) and the subcutaneous murine mammary carcinoma EMT-6. This paper presents
results demonstrating that individual microbeams, or arrays of parallel ones, can also be used for targeted, selective cell
ablation in the CNS, and also to induce demyelination. The results highlight the value of the method as a powerful tool
for studying the CNS through selective cell ablation, besides its potential as a treatment modality in clinical oncology.
r 2005 Elsevier B.V. All rights reserved.
PACS: 87.50.a
Keywords: Dosimetry; Synchrotron radiation; Micro-beam therapy
ARTICLE IN PRESS
www.elsevier.com/locate/nima
0168-9002/$ - see front matter r 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.nima.2005.03.062
Corresponding author. Tel.: +1 6313447696; fax: +1 6313445311.
E-mail address: dilmanian@bnl.gov (F.A. Dilmanian).
1
Present address: The Kennedy Krieger Institute, John Hopkins School of Medicine, Baltimore, MD 21205.
Page 1
1. Introduction and background
1.1. X-ray microplanar beams
The technique of X-ray microbeam irradia-
tion, i.e., exposing tissue to single-dose-fraction
arrays of parallel, thin (25–90 mm) planes of
synchrotron-generated X-rays (microplanar beams,
or microbeams), was developed at the X17B1
superconducting wiggler beamline of the National
Synchrotron Light Source (NSLS), Brookhaven
National Laboratory (BNL) around 1990 [1,2];it
has also been studied at the European Synchrotron
Radiation Facility (ESRF), Grenoble, France [3]
since the mid-1990s. The properties of microbeams
that make them a good candidate for tumor
therapy are (a) their sparing effect on normal
tissues, including the central nervous system
(CNS) [2–17], and (b) their preferential damage
to tumors, even when administered from a single
direction [4,7,12,14]. These concepts are depicted
in Fig. 1. The method is known as microbeam
radiation therapy (MRT) [1].
1.2. The two microbeam effects and the method’s
therapeutic index: published results
The normal-tissue sparing effect of single-frac-
tion microbeam arrays was established in the brain
of the adult rat [2,4–7,12], the cerebellum of
suckling rats [8], the CNS of duck embryos [10],
the cerebellum of piglets [11], and the skin of the
mouse [14] and the rat [15]. The preferential
tumoricidal effect of microbeams was demon-
strated in two tumor models. The first model was
the intracranial rat 9LGS tumor that was treated
using (a) a single parallel array of microbeams
(called unidirectional irradiation, or irradiation
with a co-planar array) [5,7,12], (b) two ortho-
gonal arrays crossing at the tumor (bidirectional
irradiation) [5–7], and (c) three orthogonal arrays
crossing at the tumor (tridirectional irradiation)
[6]. The second model was the subcutaneous
murine mammary carcinoma EMT-6 tumor that
was treated using two unidirectional irradiation
methods [14]:
co-planar microbeam arrays, and
cross-planar arrays, in which two arrays are
incident from the same direction on the target,
one with horizontal microplanar beams and one
with vertical ones.
Slatkin [18] recently discussed different methods
of possible clinical microbeam irradiation. The
animal studies suggested that single-fraction, uni-
directional microbeams have a larger therapeutic
index for treating the above tumors than do single-
fraction unidirectional broad beams [12,14]. The
therapeutic index is defined as the maximum dose
tolerated by normal tissues divided by the mini-
mum dose for ablating the tumor, or, alternatively,
as ED50/TCD50, where ED50 and TCD50 are the
doses that produce a 50% radiobiological effect in
normal tissues (in our case, a damage) and a 50%
effect in controlling tumors (in our case, ablating
them), respectively.
The biological processes underlying the above
two effects of microbeams are not well under-
stood. For the sparing effect of microscopic beams
in normal tissue, which Curtis et al. first estab-
lished with deuteron beams [19,20] rather than
with X-ray beams, we can confidently say that the
effect involves the rapid regeneration of the
tissue’s microvessels from cells surviving outside
the microbeams’ direct paths (for microbeam
arrays, this means survival in the ‘‘valley dose’’
regions, i.e., the spaces between individual mi-
crobeams). This effect was demonstrated in work
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Fig. 1. Schematic view of irradiating a tumor with an array of
parallel microbeams. The figure indicates the sparing effect of
microbeams in normal tissue, and their preferential tumoricidal
effect.
F.A. Dilmanian et al. / Nuclear Instruments and Methods in Physics Research A 548 (2005) 30–37 31
Page 2
at the ESRF wherein the vascular network of the
chorio-allantoic membrane of the chicken embryo
was observed in vivo following microbeam irra-
diation [13]. Furthermore, it also became clear that
the CNS and the glial system somehow recover
from the insult [2,7,8,11]. Our new studies, dis-
cussed in this paper [17,21–23], reveal more details
of this recovery.
The preferential tumoricidal effect of microbe-
ams is thought to be partly due to the failure of the
tumor’s microvessels to repair the damage inflicted
by these beams, which could then lead to the loss
of blood perfusion and tissue necrosis [7,12,14].
The effects might reflect major differences between
the microvasculature of normal tissues and tumors
in response to radiation [24,25], including (a) the
rapid proliferation of endothelial cells in tumors
which may render their microvessels more vul-
nerable to microbeam damage, and (b) the
abnormal basement membrane in the tumor’s
vasculature [25].
2. CNS effects of microbeams
2.1. Earlier results on selective neuronal cell
ablation by microplanar beams
Laissue et al. [4] and Slatkin et al. [2] were first
to report targeted, selective ablation of granular
cells in the rat’s cerebellum with high-dose X-ray
microplanar beams. Fischer 344 rats were irra-
diated anteroposteriorly (AP) with a microbeam
array with 37 mm beam width and 75 mm on-center
beam spacing. The array was arranged in alter-
nating triplet microbeams delivering 1000 and
2500 Gy in-beam incident doses to the brain. The
X17B1 beam was filtered with 0.25 mm Gd,
producing a 48.5 keV half-power energy and a
16.3 mm tissue half-value layer. Therefore, on
reaching the cerebellum, the in-beam in-depth
doses were less than half the initial incident dose.
Thirty days after exposure, the cerebella tissue was
removed, stained with hematoxylin and eosin
(H&E; staining the cell nucleus and cytoplasm,
respectively), and studied [2]. Later microbeam
studies at the NSLS and ESRF also reported such
ablation of neuronal cells; the animal models were
the cerebellum of the adult rat [7], suckling rat [8],
and piglet [11].
2.2. Present studies of cell ablations in the CNS
Here we report mainly results from two studies
in which the rat’s brain was irradiated AP with
high-dose microbeams. The first study (Experi-
ment 1) used very narrow microbeams (27 mm),
spaced 200 mm on-center at an 800 Gy in-beam
incident dose; over a limited time we followed the
course of microbeam-induced granular cell abla-
tion in sections from the cerebellum, stained with
hematoxylin [17]. In the second experiment we
employed a single, much wider microplanar beam
(270 mm) at 750 Gy dose, and followed the ablation
of oligodendrocytes and astrocytes in the rat
brain’s white matter. We also briefly discuss a
study of the rat’s spinal cord irradiated with
270 mm wide high-dose microbeams to assess
demyelination and remyelination, in addition to
the loss and recovery of the glial cell populations.
Experiment 1 was carried out in collaboration with
Drs. Cool, Kruse, and Sze of University of
Colorado Health Sciences Center (UCHSC).
Experiment 2 was carried out in collaboration
with both UCHSC and Dr. John McDonald and
his group at Washington University, and the
spinal cord study [21–23] was carried out in
collaboration with Dr. John McDonald and his
group.
3. Experimental design
3.1. Beam energy considerations
For a given synchrotron source the beam’s
energy is determined by the amount of beam
filtration used. Because of the trade-off between
the beam’s energy and dose rate, the main
consideration in choosing the filtration naturally
is the dose rate needed for a particular study.
However, even if the synchrotron source and the
dose-rate requirement allow it, the beam’s energy
cannot be raised beyond the limit at which it
increases the array’s valley dose to an undesirable
level in the normal tissue. This consideration is
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F.A. Dilmanian et al. / Nuclear Instruments and Methods in Physics Research A 548 (2005) 30–3732
Page 3
more important for smaller values of beam width
and spacing (e.g., 30 and 100 mm, respectively).
To clarify this point, we present the findings
from Monte Carlo simulations of dose distribution
in a water phantom produced by a microbeam
array of 30-mm beam width and 200 mm beam
spacing (Fig. 2). The code used was the upgraded
EGS4 [26–28], and the routine was similar to those
used in the earlier studies at BNL [1,29]. The
simulations show a single period of the array’s
dose distribution, from one beam’s center to
another. The phantom was 16 16 cm, and the
array size was 30 30 mm, impinging on the
phantom’s flat side and being centered symmetri-
cally about the cylinder’s axis. The observation
region was at the center laterally, and 7.5–8.5 cm
deep into the phantom. The simulations were
carried out with monochromatic beams of 75, 150,
and 200 keV. An important feature of the resulting
plots is the rounding of the edges of the beams at
the top and the bottom of the fall-off curves; these
effects are produced by the finite range of the
photoelectrons and Compton electrons, set in
motion by the incident X-ray photons. These
results clearly show that already at 150 keV, and
unequivocally at 200 keV, these electrons produce
considerable rounding of the edges of the valley
dose region, although the value at the bottom of
the valley in this configuration still is produced by
the photoelectrons and Compton electrons of the
scattered photons and not the incident ones. If
these results are gradually extrapolated to higher
beam energies, especially after reducing the beams’
spacing (e.g., to 100 mm), an energy is soon reached
at which the rounding of the valleys’ edges
dominates the entire valley dose. Because the
valley dose in the normal tissue should be kept
below the threshold dose for tissue damage, the
effect sets an upper limit for the beam’s energy for
a given beam width/spacing. In general, 250 keV
should be considered as an upper limit for
microbeam configurations similar to those appear-
ing in the literature.
3.2. Irradiation set-up
The studies presented here were carried out at
the NSLS’s X17B1 superconducting wiggler beam-
line. The storage ring operated at 2.8 GeV and the
superconducting wiggler operated at 4.3 T. The
beam was filtered with 3.17 mm of silicon and
6.35 mm of copper, producing a half-power energy
of about 120 keV and a dose rate of about 50 Gy/s
at the site for the subject, about 30 m from the
source.
3.3. Design of experiment 1
Male Fischer 344 rats, 200–225 g, were irra-
diated AP with a 10 10 mm unidirectional array
of microbeams of 27 mm width, 200 mm spacing
[17]. The beam was produced from a broad beam
using a tungsten multislit collimator manufactured
by Tecomet [30], the manufacturer of the multislit
collimator used in our earlier works [14,15]. The
collimator was 5 mm thick in the direction of the
beam, and produced an array of vertical micro-
planar beams, 1.5 mm high and up to 50 mm wide.
The in-beam incident dose used was 800 Gy,
attenuating to about 560 Gy at the depth of the
cerebellum. Two rats were studied at the following
times after exposure: 3 h, 2, 4, and 16 d. No acute
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Fig. 2. Monte Carlo simulations of the dose distribution from
an array of parallel microbeams in a cylindrical water phantom
using the EGS4 code of photon- and electron-transport. The
figure represents the dose distribution for one complete period
of the array.
F.A. Dilmanian et al. / Nuclear Instruments and Methods in Physics Research A 548 (2005) 30–37 33
Page 4
dose effects were observed. The rats were eutha-
nized, using a CO
2
–O
2
mixture. Their brains were
removed, fixed in formalin, and axial cuts of tissue
were embedded in paraffin. Serial sections (5 mm)
were made and stained with hematoxylin.
3.4. Design of experiment 2
The second experiment was designed to show
the targeted ablation of oligodendrocytes and
astrocytes in the white matter of the rat’s brain.
The animals were irradiated AP with a single,
vertical microplanar beam 270 mm wide (actually,
three 90 mm beams side-by-side) and 11 mm high at
an entrance dose of 750 Gy. Following euthanasia
of groups of animals at one week, three weeks, and
three months by tissue perfusion with phosphate
buffered saline (PBS) and then 10% buffered
formalin, the brains were sectioned sagittally,
embedded in paraffin, and sectioned at 5 mm. The
sections were stained with immunofluorescent
labeling specific to oligodendrocytes and astro-
cytes.
4. Results
4.1. Results of experiment 1
The results are shown in Figs. 3–7. The 3-h time-
point cerebellum tissues stained with hematoxylin
already showed the microbeams’ paths as bands of
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Fig. 3. Path of a microbeam in the cerebellum 3 h post-
irradiation seen as darkened cerebella granular cells (400 ).
Fig. 4. Microbeam’s path seen in the cerebellum 2 d post-
irradiation (400 ).
Fig. 5. Microbeam’s path in the cerebellum 4 d post-irradia-
tion. Some neurons have disappeared (400 ).
Fig. 6. Microbeam pattern of banding seen in the cerebellum
16 d post-irradiation. Almost all neurons had disappeared,
leaving a strong white band (arrows) (200 ).
F.A. Dilmanian et al. / Nuclear Instruments and Methods in Physics Research A 548 (2005) 30–3734
Page 5
cell with hyperchromatic nuclei (Fig. 3), represent-
ing neurons gradually undergoing necrotic death
[17]. The staining for hyperchromatic cells was
more intense at 2 d (Fig. 4), but by 4 d the density
of these cells started to decrease (Fig. 5). By day
16, the beams’ paths were represented by hypo-
chromatic bands of missing nuclei in the tissue
(Fig. 6). Fig. 7 shows a tissue section similar to
that of Fig. 6 in which two intact capillary blood
vessels are seen crossing these former microbeam
paths; this observation is evidence for the regen-
eration of the capillaries after irradiation. The
banding effect in the cerebrum was visible,
although much less pronounced (Fig. 8). This
lesser response, which we had also previously
observed in the microbeam-irradiated rat’s brain,
is partly attributed to the comparative paucity of
neurons in the cerebrum; cerebral banding became
visible only after 3 weeks.
4.2. Results of experiment 2
Fig. 9 shows the results of immunohistochemical
studies of white matter tissue in the rat brain
(midsagittal sulcus), one week after irradiation.
The panel shows from left to right, immunofluor-
escent labeling for adenomatous polyposis coli
(APC; oligodendrocytes; red), glial fibrillary acid
protein (GFAP; astrocytes; green), Hoechst nucle-
ar counterstaining (blues), and the triple overlay.
The loss of putative oligodendrocytes (APC
+
) and
astrocytes (GFAP
+
) within the beam’s path and
their preservation just outside it are clear. At two
months (not shown) these cell populations were
largely restored.
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Fig. 7. Similar to Fig. 6, but also showing two undamaged
capillary blood vessels crossing the microbeam-induced tracks
(arrows) (200 ).
Fig. 8. Microbeam pattern of banding seen in the cerebrum 3
weeks post-irradiation (arrows) (200 ).
Fig. 9. Schematic horizontal section of the rat brain showing the position of the microbeam just lateral to the midsaggital sulcus. Loss
of putative oligodendrocytes (APC+) and astrocytes (glial fibrillary acidic protein, GFAP+) one week after exposure to a 270 mm
wide, 650 Gy microbeam in the white matter of the rat brain (midsaggital sulcus) (work carried out in collaboration with John
McDonald et al., Washington University).
F.A. Dilmanian et al. / Nuclear Instruments and Methods in Physics Research A 548 (2005) 30–37 35
Page 6
4.3. Microbeam-induced demyelination and
subsequent remyelination in the rat’s spinal cord
Male Fischer 344 rats were irradiated with a
single microplanar beam, or up to 4 parallel ones,
of a 270 mm wide beam at high doses including a
1000 Gy incident dose (about 750 Gy in-depth
dose) [21–23]. Two weeks later, oligodendrocytes
and astrocytes had been selectively ablated and
myelin was destroyed in the microbeam’s path, as
detected by immunofluorescence techniques; at
three months, uniform repopulations of the glial
cells, and remyelination, were observed. No
vascular damage was seen, and no axonal loss
was detected of white matter [21–23]; therefore the
tissue’s cytological features were intact except for
the early-stage loss of glial cells or myelin within
the microbeam slice.
5. Discussion and conclusions
The body of evidence already appearing in the
literature on microbeam effects studied in different
normal and cancerous tissues points to the
potential of microbeam in clinical radiation
therapy. This potential is based on the remarkable
tolerance of normal tissues to microbeams, and on
the larger therapeutic index for MRT over
conventional beams found in treating two types
of malignant tumors. However, any particular
application must overcome problems such as (a)
keeping the valley dose adequately low in the
normal tissue, which may not be easy for large
and/or deeply seated tumors, (b) minimizing the
effects of cardiosynchronous body pulsation,
which might be achieved by administering the
entire dose in a fraction of heart beat or by
cardiac-gated irradiation and (c) mitigating the
effects of a high dose to the proximal tissue that is
needed because of the beams’ relatively low
energy, and thus more limited dose penetration
to the tissue. The solutions may be in finding the
right clinical applications, and the right irradiation
geometries. MRT is currently considered one of
the most exciting applications of synchrotron X-
rays in medical research [3,31].
The potential of microbeams for CNS research
is also very large, based on the findings presented
here and by other investigators. In particular, our
results show that microbeams can selectively
ablate slices of neurons, oligodendrocytes, and
astrocytes in the CNS because of the differential
dose sensitivity of different cell types, without
causing tissue necrosis. In other words, by adjust-
ing the dose one can selectively ablate different cell
types. Also, our results show that microbeams can
induce temporary demyelination in two weeks
without axonal or vascular damage, with remye-
lination following in 3 months post-irradiations.
The effects are a further indication of the recovery
of the normal tissue’s microvasculature after
exposure to microbeam irradiation, especially
from transient damage to the capillaries. This
recovery constitutes the basis for restoring the
tissue’s viability, and therefore its complete resti-
tution; it signifies that the normal tissue remains
viable (i.e., in terms of blood perfusion and
metabolic activities) even though slice(s) of neu-
rons or glial cells were ablated (i.e., there is no
‘‘pan necrosis’’). Because no other method can
ablate the glial cells and cause demyelination
without concomitantly inducing some damage in
the tissue’s structure, we conclude that microbe-
ams offer a unique tool for studying the effects of
selective removal of mitotic and non-mitotic cells
in the CNS and other tissues.
Acknowledgements
We thank T. Bacarian, M.E. Berens, A. Feld-
man, C. Garibotto, T. George, J. Giordano, S.
Hussain, Z. Hussain, Y. Kublanskaya, S. Leroy,
R. Maehara, P. Mortazavi, A. Nithi, I. Orion, S.
Rafiq, B. Ren, E.S. Rosenzweig, J.K. Robinson,
A. Ruvinskaya, T. Steidinger, S. Thomas, J.
Welwart, D. Williams, A.D. Woodhead, and R.
Yakupov for their valuable assistance. These
studies were funded by the Nextsteps Foundation,
IL (JWM), the National Institute of Health
NINDS grants NS37927, NS40520, NS39577
(JWM) and NS43231 (FAD), and the Office of
Biological and Environmental Research, U.S.
Department of Energy. This research was carried
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F.A. Dilmanian et al. / Nuclear Instruments and Methods in Physics Research A 548 (2005) 30–3736
Page 7
out at the NSLS which is supported by the U.S.
Department of Energy, Division of Materials
Sciences and Division of Chemical Sciences, under
Contract No. DE-AC02-98CH10886.
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ARTICLE IN PRESS
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    • "In this case, cells receive signals that make them respond and migrate to the damaged area in order to recover the whole cells' monolayers. At tissue levels, there are more complex repair systems involved in the normal tissue sparing effects of MRT, as shown by many experimental studies222324. In this study, we observed that the addition of AuNP promotes such " artificial wound " repair and cells impregnated with AuNP responded differently. "
    [Show abstract] [Hide abstract] ABSTRACT: The focus of this research was the enhancement of radiation dose for microbeam radiotherapy (MRT) by the inclusion of gold nanoparticles (AuNPs) in the target. Microbeam radiotherapy is a technique that employs a very high dose rate of X-rays to kill highly resistant tumours such as glioma without jeopardizing the tolerance of normal tissue. The reduction of radiation dose rate used in this technique by using AuNPs may enhance the normal tissue tolerance while achieving better tumour control. In this study, microbeam kilovoltage X-ray of mean energy 125 keV from the SPring8 Synchrotron in Japan was used. The results show dose enhancement effects on endothelial cells by AuNPs which are consistent with previously documented results using broad beams of X-rays. It was also observed in this study that the inclusion of AuNPs accelerates cell migration towards the eradicated area which is important in normal tissue recovery. The phenomenon of cell migration is observed when cell fill depleted gaps that have been created by the microbeams or when such gaps are manually made by scratching the cell culture as a wound. The reason behind this acceleration of the rate of gap fillings is not well understood. However, it has been attributed to various biological processes and has also been thought of as being partially due to the effects of electrostatic charge of such particles. It could also be the combined effects of biological and electrostatic effects due to the charges of the particles inside the cells. Moreover, it is also observed that the cancerous glioma cell fills the gaps in much slower rates in comparison to the normal endothelial cells. This is consistent with the notion on which the MRT techniques are based. KeywordsGold nanoparticles–Microbeam radiotherapy–Dose enhancement–Cellular migration
    Full-text · Article · Jun 2011 · BioNanoScience
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    • "It is assumed that the microvasculature in the paths of the beams is regenerated from the angiogenic cells surviving between the paths of the beams (Serduc et al 2006, 2008b, Slatkin et al 1995). However, this is not observed in tumour tissue and microvessels of the tumour are damaged which can lead to the loss of blood perfusion and tissue necrosis (Dilmanian 2005). The dose administered in the beam's path is named 'peak dose' and the dose administered between two adjacent beams is named as 'valley dose'. "
    [Show abstract] [Hide abstract] ABSTRACT: In this study, dose distribution calculations for bidirectional interlaced microbeam radiation therapy (BIMRT) were performed with a detailed head phantom model and the Monte Carlo code MCNPX. Doses were calculated in intracranial targets of dimensions 20 × 6.8 × 20 mm³ and 20 × 20 × 20 mm³ and surrounding tissue for which interlacing arrays are composed of 5 and 15 microbeams, respectively. Simulations were performed with a realistic head phantom and a homogenized head phantom of the same outer shape to study the effects of the structure of the realistic phantom on dose distribution and to show how important it is to use realistic phantoms. Depth-dose profiles and dose falloffs at the edges of the targets were calculated for cases with and without an Au contrast agent deposited in the target region and surrounding tissue. The parallel pattern of the microbeam arrays was preserved through the head phantom which makes it possible to interlace microbeam arrays even at deep seated targets. As the dimensions of the target volume were increased, the valley dose values increased with the number of microbeams. This sets limits on the size and position of the target. The usage of gold as a contrast agent provided a substantial increase in target dose and decreased the skin entrance, maximum skull bone and maximum brain doses inevitable to produce the desired target dose. Short dose falloffs at the edges of the targets were preserved for all cases.
    Preview · Article · Dec 2010 · Physics in Medicine and Biology
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    • "1. Microbeams can selectively ablate slices of neurons, oligodendrocytes, and astrocytes in the CNS, without causing tissue necrosis. It has been reported that microbeams can induce temporary demyelination in two weeks without axonal or vascular damage, with remyelination following in 3 months post-irradiation [25]. Similarly, in the rat spinal cord exposed to a 270 mm-thick planar beam (entrance dose 740 Gy), proliferation, migration and differentiation of progenitor glial cells could have promoted production of new, mature and functional glial cells and consecutive remyelination [26]. "
    [Show abstract] [Hide abstract] ABSTRACT: Microbeam radiation therapy (MRT) uses highly collimated, quasi-parallel arrays of X-ray microbeams of 50–600 keV, produced by third generation synchrotron sources, such as the European Synchrotron Radiation Facility (ESRF), in France. The main advantages of highly brilliant synchrotron sources are an extremely high dose rate and very small beam divergence. High dose rates are necessary to deliver therapeutic doses in microscopic volumes, to avoid spreading of the microbeams by cardiosynchronous movement of the tissues. The minimal beam divergence results in the advantage of steeper dose gradients delivered to a tumor target, thus achieving a higher dose deposition in the target volume in fractions of seconds, with a sharper penumbra than that produced in conventional radiotherapy.
    Full-text · Article · Apr 2010 · Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
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