U.S. patent application number 09/813094 was filed with the patent office on 2002-02-28 for device for non-invasive analysis by radio-imaging, in particular for the in vivo examination of small animals, and method of use.
Invention is credited to Charon, Pierre Yves, Laniece, Philippe, Mastrippolito, Roland, Pinot, Laurent, Ploux, Lydie, Siebert, Rainer, Tricoire, Herve, Valda Ochoa, Alejandro Anibal, Valentin, Luc.
Application Number | 20020024024 09/813094 |
Document ID | / |
Family ID | 9480170 |
Filed Date | 2002-02-28 |
United States Patent
Application |
20020024024 |
Kind Code |
A1 |
Mastrippolito, Roland ; et
al. |
February 28, 2002 |
Device for non-invasive analysis by radio-imaging, in particular
for the in vivo examination of small animals, and method of use
Abstract
A non-invasive analysis device including a plurality of sensors
(110) combined with collimating structures (120) having a common
source focus (O) and processing means (300) providing an AND-type
combinational logic function of the output of the sensors (110) for
sensing two coincidently transmitted beams that are at least
slightly angularly correlated.
Inventors: |
Mastrippolito, Roland;
(Montigny Le Bretonneux, FR) ; Ploux, Lydie; (Le
Mans, FR) ; Charon, Pierre Yves; (Gif-Sur-Yvette,
FR) ; Pinot, Laurent; (Lardy, FR) ; Valentin,
Luc; (Bures-Sur-Yvette, FR) ; Valda Ochoa, Alejandro
Anibal; (Villalba, ES) ; Siebert, Rainer;
(Port Marly, FR) ; Laniece, Philippe; (Paris,
FR) ; Tricoire, Herve; (Palaiseau, FR) |
Correspondence
Address: |
BLAKELY SOKOLOFF TAYLOR & ZAFMAN
12400 WILSHIRE BOULEVARD, SEVENTH FLOOR
LOS ANGELES
CA
90025
US
|
Family ID: |
9480170 |
Appl. No.: |
09/813094 |
Filed: |
March 19, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09813094 |
Mar 19, 2001 |
|
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08981387 |
Apr 13, 1998 |
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6225631 |
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Current U.S.
Class: |
250/515.1 |
Current CPC
Class: |
G21H 5/02 20130101; A61B
6/508 20130101; G01T 1/2985 20130101; A61B 6/4258 20130101; G21K
1/025 20130101 |
Class at
Publication: |
250/515.1 |
International
Class: |
G21F 001/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 20, 1995 |
FR |
95 07345 |
Claims
1. Device for non-invasive analysis, characterized in that it
comprises a plurality of detectors (110) which are associated with
collimating structures (120) having a common source focus (O) and
processing means (300) performing a combinatorial logic function of
the "AND" type on the output of the detectors (110) in order to
detect two coincidentally emitted radiation events that are at
least slightly angularly correlated.
2. Device according to claim 1, characterized in that it comprises
means for counting radioactive radiation events.
3. Device according to one of claims 1 or 2, characterized in that
it further comprises means (200) which are designed to support the
body (C) to be analyzed, and to allow a controlled relative
displacement between it and the set of detectors (110).
4. Device according to one of claims 1 to 3, characterized in that
the detectors (110) cover a spatial field at least equal to 2.pi.
steradians around the focus (O).
5. Device according to one of claims 1 to 4, characterized in that
the detectors (110) are arranged in accordance with the faces of an
icosahedron.
6. Device according to one of claims 1 to 5, characterized in that
it comprises fifteen detectors (110).
7. Device according to one of claims 1 to 6, characterized in that
each detector (110) comprises a collimator (120), a scintillator
(130), an optical guide (135) and a photomultiplier (140).
8. Device according to one of claims 1 to 7, characterized in that
each collimating structure (120) comprises conical radial holes
(124).
9. Device according to one of claims 1 to 8, characterized in that
it comprises a structure (150) which is intended to support the set
of detectors (110) and is in the form of a framework consisting of
bars (152) connected by their ends.
10. Device according to one of claims 1 to 9, characterized in that
it comprises means (200) which can effect a relative displacement
which is controlled and identified on the basis of three orthoganol
axes between the body (C) to be analyzed and the set of detectors
(110).
11. Device according to one of claims 1 to 10, characterized in
that it comprises processing means (300) comprising energy/time
conversion means (320) which can encode the detected events in the
form of signals whose width is proportional to the energy of the
event.
12. Device according to claim 11, characterized in that the
processing means (320) comprise: a capacitor (321) capable of
integrating the signal output by a photomultiplier (140), an output
signal detector (322) for the photomultiplier, a delay cell (323)
initiated by the aforementioned detector (322), a current source
(324) which is connected in parallel with the capacitor (321) and
is driven by the output of the delay cell (323), a comparator
(325), one input of which is grounded and the other input of which
is connected to the capacitor (321), the output of this comparator
(325) constituting the output of the energy/time conversion device,
and a switch (326) which is controlled by the comparator (325) and
can discharge the capacitor (321).
13. Device according to one of claims 11 and 12, characterized in
that the processing means (300) comprising timers (334, 335) which
are driven by a clock (333) and are designed to define the trip
times of the signal output by the energy/time conversion means
(320).
14. Device according to claim 13, characterized in that the timers
(334, 335) are controlled by detectors (331, 332) of leading and
trailing edges of the signals output by the energy/time convertors
(320).
15. Collimator for a radio-imaging analysis device, characterized
in that it is formed by a stack of plates (122) provided with
perforations (124).
16. Collimator according to claim 15, characterized in that the
perforations (124) provided in the various plates (122) exhibit a
homothetic progression.
17. Collimator according to one of claims 15 and 16, characterized
in that the perforations (124) are produced by chemical
machining.
18. Collimator according to one of claims 15 to 17, characterized
in that the plates (122) are made of tungsten.
19. Collimator according to one of claims 15 to 18, characterized
in that the thickness (d) of the plates (122) is less than the
diameter of the perforations (124) in the internal entry face (123)
of the collimator and the span between the perforations (124) is
greater than the thickness of the plates (12).
20. Collimator according to one of claims 15 to 19, characterized
in that at least some of the plates (122) are formed by
superposition of two identical perforated screens.
21. Analysis method, characterized in that it comprises the steps
consisting in: injecting, into a body (C) to be analyzed, a marker
which can generate two coincidentally emitted radiation events that
are at least slightly angularly correlated, and detecting these
radiation events using an analysis device comprising a plurality of
detectors (110) which are associated with collimating structures
(120) having a common source focus (O) and processing means (300)
performing a combinatorial logic function of the "AND" type on the
output of the detectors (110) in order to detect two coincidentally
emitted radiation events that are at least slightly angularly
correlated.
22. Method according to claim 21, characterized in that the marker
which is used is designed to emit two coincidentally emitted
radiation events that are at least slightly angularly correlated
through atomic (X emitted following electron capture or internal
conversion) or nuclear origin (gamma emitted during the isobaric
de-excitation of a nucleus).
23. Method according to one of claims 21 and 22, characterized in
that the marker which is used is chosen from the group comprising
.sup.123I, .sup.125I, .sup.111In.
24. Method according to one of claims 21 to 23, characterized in
that the image of the body to be analyzed is constructed voxel by
voxel.
Description
[0001] The present invention relates to the field of non-invasive
devices for analysis by radio-imaging.
[0002] Numerous analysis devices have already been proposed which
use radioactive markers (Geiger counters coupled to a collimator,
gamma cameras, etc.).
[0003] By utilizing the inherent property of radioactive marking
which makes it possible to obtain quantitative information
regarding the distribution of the tracer, radio-imaging techniques
constitute an important tool both in the clinical field and in the
field of fundamental research.
[0004] At present, the devices which are used most widely in this
field belong to computer-aided emission tomography.
[0005] Computer-aided tomography has been developed along two
different lines: the SPECT (Single Photon Emission Computed
Tomography), which uses radio isotopes emitting a single photon by
decay, for example .sup.99mTc, and the PET (Positron Emission
Tomography) system, which uses radio isotopes in which two gamma
radiation events are emitted simultaneously during the
annihilation, in the tissue, of the positron produced by the decay
of, for example, .sup.18F.
[0006] Most SPECT systems are based on the use of one or more gamma
cameras which are rotated about the object to be analyzed. A
typical gamma camera consists of a multi-channel collimator, a
large-area scintillator crystal, a light guide for optical coupling
between the crystal and a set of photomultiplier tubes, and analog
electronics for analyzing the amplitude of the signal and the
position encoding. The entire device is contained within lead
shielding in order to minimize the background noise produced by
sources lying outside the field of view of the camera. The
operating principle of a gamma camera is as follows: a photon,
produced by a decay event in the source and passing through the
collimator, can interact with the scintillator, provoking a local
and isotropic scintillation. The photomultiplier tubes located
above each receive a light flux which depends on their distance
from the light source. It is then possible, on the basis of the
electrical signals delivered by each photomultiplier, to
reconstruct the position of the scintillation by a
center-of-gravity technique and to record and/or send it to a
display device.
[0007] Positron emission tomography (PET) is another method which
makes it possible to achieve in vivo and non-invasive regional
measurement of physiological and metabolic parameters.
Positron-emitter radioelements are isotopes having a surplus of
protons with respect to their number of neutrons. When a positron
is almost at rest, an encounter with an electron gives rise to an
annihilation reaction which produces the simultaneous emission of
two gamma photons departing in almost opposite directions. PET
systems thus comprise an array of detectors in a ring which can
detect the coincidence of two photons, as being indicative of the
emission of the positron. The site of the annihilation then lies
somewhere in the volume defined between the two detectors in
question.
[0008] Radio-pharmaceutical imaging constitutes an important tool
in the diagnosis, characterization and treatment of diseases and
functional disorders. However, before new pharmacological agents
are used in man, it is generally necessary to characterize them in
animal models in order to determine its biochemical, metabolic and
physiological effects.
[0009] Of course, this characterization presupposes the
availability of high-resolution imaging techniques in order to
evaluate, ex vivo or in vivo, the spatial concentrations of the
tracer which is injected.
[0010] At the present time, the spatial resolution of conventional
tomographs is from 5 to 7 mm in the case of PET systems and from 8
to 12 mm in the case of SPECT systems. These values prove to be
insufficient for carrying out studies in small animals, for example
for rat studies of tumors, the typical size of which is of a few
mm, or the distribution of neuroreceptors. In actual fact, it is
necessary for a tomograph dedicated to the imaging of small animals
to be able to provide spatial resolutions of at least .about.2
mm.
[0011] Since 1990, a number of approaches based on PET and SPECT
systems have been pursued in an attempt to achieve the desired
performance.
[0012] However, these attempts at improvement have not yet been
satisfactory, except at the cost of detection efficiency. The
limitations of current tomographs in terms of resolution do not
therefore allow in vivo studies to be extended to models on small
animals, for which experimentation could be carried out more
precisely.
[0013] The object of the present invention is to improve this
situation.
[0014] This object is achieved according to the present invention
by virtue of an analysis device comprising a plurality of detectors
which are associated with collimating structures having a common
source focus and processing means performing a combinatorial logic
function of the "AND" type on the output of the detectors in order
to detect two coincidentally emitted radiation events that are at
least slightly angularly correlated.
[0015] According to an advantageous characteristic of the
invention, a multi-channel collimator is provided which is formed
by a stack of plates having homothetic perforations.
[0016] According to another characteristic of the invention, the
perforations in the plates are produced by chemical machining.
[0017] The present invention also relates to an analysis method
which comprises the steps consisting in:
[0018] injecting, into a body to be analyzed, a marker which can
generate two coincidentally emitted radiation events that are at
least slightly angularly correlated, and
[0019] detecting these radiation events using a device of the
aforementioned type.
[0020] Other characteristics, objects and advantages of the present
invention will emerge when reading the following detailed
description, and with reference to the appended drawings which are
given by way of non-limiting example, and in which:
[0021] FIG. 1 represents a general schematic view of an analysis
device according to the present invention,
[0022] FIG. 2 represents a view, partially in section, of the
detection part of this device,
[0023] FIG. 3 schematically represents a stack of plates forming a
collimator,
[0024] FIG. 4 represents a structure for supporting of the
detectors,
[0025] FIG. 5 represents a partial diagram of the processing of an
acquisition circuit according to a first variant of the
invention,
[0026] FIG. 6 schematically represents one form of energy/time
conversion of the detected signals, according to a second variant
of the invention,
[0027] FIG. 7 represents a circuit diagram for this purpose,
[0028] FIG. 8 represents time diagrams of the signals of this
circuit, and
[0029] FIG. 9 represents the general structure of an acquisition
circuit.
[0030] The analysis device according to the present invention
essentially comprises:
[0031] a set of detectors 100,
[0032] means 200 which are designed to support a body C to be
analyzed and to allow a controlled relative displacement between it
and the set of detectors 100, and
[0033] processing means 300.
[0034] The set of detectors 100 comprises a plurality of detectors
110 focused on a common source focus O. The detectors 110 are
carried by a support structure 150.
[0035] The detectors 110 preferably cover a solid angle at least
equal to 2.pi. steradians around the focus O.
[0036] According to the non-limiting particular embodiment
represented in the appended figures, fifteen detectors 110 are
provided, arranged in correspondence with fifteen adjacent faces of
an icosahedron.
[0037] Each detector 110 preferably comprises:
[0038] a collimator 120,
[0039] a scintillator 130,
[0040] an optical guide 135, and
[0041] a photomultiplier 140.
[0042] A detector 110 of this type constitutes a counter of gamma
and/or X radiation.
[0043] The collimators 120 are used to select the direction of the
photons which are detected. They are formed by collimating
structures that focus with large solid angle.
[0044] The focused collimation allows preferential detection of the
radiation originating from a small region of space around the focal
point O. A collimating structure of this type may be formed by a
spherical cap with sectors or a polyhedron consisting of plane
parts pierced with conical radial holes and constructed with a
material having high photoelectric absorption power.
[0045] The conical radial holes preferably have at least
substantially the same entry radii. They also preferably have at
least substantially the same exit radii, the same vertex and are
juxtaposed in a regular array with axial symmetry. The various
channels are separated by partitions whose thickness is tailored to
the energy of the radiation emitted by the source, so as to make it
possible to absorb a high proportion of those protons whose
trajectory is oblique with respect to the channel axis. In this
way, only the photons emitted at the focal point will have a
significant probability of reaching the scintillators 130.
[0046] In the scope of the present invention, as schematized in
FIG. 3, the collimators 120 are preferably made by stacking
perforated plates 122 having homothetic perforations 124.
[0047] The plates 122 are advantageously made of tungsten.
[0048] The reason for choosing tungsten is, on the one hand, its
high absorption power: it has an absorption coefficient which is
30% to 40% greater than that of lead in the 10-500 keV range.
Further, its mechanical properties ensure that the system is rigid
and that the shape of the holes 124 is precise.
[0049] Moreover, within the scope of the invention, the homothetic
perforations 124 made in the tungsten plates 122 are preferably
obtained by chemical machining.
[0050] After lengthy studies and experiments, this technique was
found to be superior to other known piercing techniques, such as
laser piercing or wire spark erosion.
[0051] Machining by chemical etching consists in depositing a
photosensitive resin on all the parts which are to be preserved, by
making use of a mask representing the part to be produced. The part
is then immersed in a bath which chemically etches the unprotected
regions to form the desired openings 124.
[0052] As schematized in FIG. 3, the holes 124 in each plate 122
are cylinders that are parallel to one another and orthogonal to
the faces of the plates 122. The result of this is that the solid
angle, with respect to the source focus O, subtended by the
aperture of a hole 124, decreases when moving away from the normal
N to the plates 122 which passes through their homothetic center
O.
[0053] The radius r of the holes 124 in the entry face 123, the
thickness d of the plates 122 and the focal length f are determined
so as to conserve an acceptable solid angle subtended by the
aperture of each hole 124 with respect to O.
[0054] The thickness d of the plates 122 is preferably less than
the diameter of the holes 124 in the internal entry face 123 of the
collimator, for example equal to half this diameter, and the
thickness of the span (septum) between the holes 124, in this
internal face 123, is greater than or equal to the thickness of the
plates 122 (i.e., for example, a distance between the centers of
the holes to equal to three times the radius of the holes 124 on
the internal face 123).
[0055] If the detectors 110 are assembled on a polyhedral support
150 of the regular icosahedron type, each collimation module 120
takes the form of a truncated triangular pyramid.
[0056] According to one non-limiting particular embodiment, each
collimator 110 is formed by stacking 48 tungsten plates 122 having
a thickness of 0.2 mm and an array of holes 124 defining a focal
length f of the order of 7 cm, the holes 124 having, in the
internal face 123 of the collimator, a radius of the order of 0.2
mm and an interaxial distance of the order 0.5 mm.
[0057] More precisely, each collimator 110 may be formed by
stacking 24 different pairs of pairwise identical plates 122. In an
arrangement of this type, each plate, of thickness d, is formed by
juxtaposing two identical screens of thickness d/2. In this way, it
is easy to produce holes 124 of diameter equal to d, with a
separation between centers equal to 3d/2.
[0058] Yet more precisely, according to a non-limiting very
particular embodiment, the radius of the holes 124 is 0.205 mm in
the first plate 122 and 0.231 mm in the last plate 122, the
distance between centers of the holes 124 is 0.614 mm in the first
plate 122 and 0.693 mm in the last plate 122, the length of the
edges of the first plate 122 is 87.2 mm and 98.3 mm for the last
plate 122, and the distance to the focal point is 71.6 mm for the
first plate 122 and 80.8 mm for the last plate 122.
[0059] The scintillator 130 is preferably formed by a single
crystal of thallium-activated sodium iodide (NaI(Tl)).
[0060] In the case of an arrangement of the icosahedral type, the
scintillator crystal has the form of a prism with triangular cross
section in order to cover the entire exit surface of the
collimator.
[0061] The light guide 135 provides optical coupling between each
scintillator crystal 130 and the associated photomultiplier tube
140.
[0062] The structure 150 which supports the detectors 110 has to
position the focal points of the collimators 120 with sufficient
precision, typically of the order of 0.1 mm. There are a number of
possible alternative embodiments for a support structure 150 of
this type.
[0063] One particular embodiment, comprising a framework consisting
of support bars 152 connected in sets of 5 by their ends and
arranged along the edges of an icosahedron, is represented in FIG.
4. The plates 122 of the collimators 120 can be fixed on these bars
152 using rods 154 engaged in the corners of the plates 122.
[0064] However, as a variant, the structure 150 may support the
light guides 135 of the detectors, instead of the collimators
120.
[0065] The system 200 for supporting and displacing the analyzed
object is designed to define three degrees of freedom in linear
displacement for the analyzed object C with respect to the sensors
110. These displacements can be brought about using three
controlled and identified motorized shafts, schematically
represented at 120 in FIG. 1, which are mutually orthogonal and
associated with control means 220 which displace the motors
interactively in order to position the object C and define an
analysis region and a displacement step in order to automatically
carry out the scan needed for acquisition.
[0066] The mechanism 210 for displacing each shaft may be composed
of the following units for each motorized shaft:
[0067] a translation table which drives the movement of a carriage
by a screw/nut system, over a travel of, for example, 10 cm,
and
[0068] a stepper motor which allows controlled increments of, for
example, 10 .mu.m on each translation table.
[0069] The image resulting from an acquisition is constructed on
the basis of the number of photons detected at each position of the
displacement system 210. During the acquisition, it is therefore
necessary to avoid any movement of the analyzed object C with
respect to the displacement system 210, so as not to introduce
artefacts in the image.
[0070] The system 200/210 consequently needs to be equipped with a
system for specific positioning of the analyzed object.
[0071] By way of non-limiting example, in the case of imaging the
brain of a rat, it is simply sufficient to immobilize the rat's
head. The positioning system used in this case may correspond to
those which are known in stereotaxy equipment. In this case, the
head is immobilized at three points: at the entries of the
auricular orifices, with two bars of adjustable position, and
behind the incisors, with a bar on which the upper jaw bears.
[0072] The processing means 300 are designed to detect two
temporally coincident radiation events produced on all of the
detectors 110, without possibly taking into consideration
coincidences produced in the same detector or those produced in
diametrically opposite detectors.
[0073] An event is thus detected with all the more probability that
it originates from the focal point by virtue of the combination of
physical collimation, given by the collimating structure, and
electronic collimation, given by the coincident detection of the
photons produced by the decay.
[0074] When two photons of equal energy are to be detected, the
processing and acquisition electronics 300 may be particularly
simple, as represented in FIG. 5.
[0075] Each detection line associated with a detector 110 comprises
an amplifier 310 and a discriminator module 312 which define a
window around the photopeak. The outputs of the single-channel
analyzers 312 are used to generate the coincidence signal in a
time/amplitude converter 314. Three signals are sent to an
interface card 316: the coincidence signal output by the converter
314 and the two outputs of the single-channel analyzers 312, in the
latter case with the object of constructing a single-photon image
for each detector 110. An acquisition signal, generated by logic
combination in a gate 318 of the single-event images originating
from the discriminators 312, is also applied to the interface card
316.
[0076] The device which has been described above and is illustrated
in FIG. 5 nevertheless soon becomes bulky and impractical when the
intention is for coincident detection, and from more than two
detectors 110, of two radiation events of different energy.
[0077] In order to resolve this difficulty, a specific acquisition
device is proposed in the scope of the invention, which makes it
possible, for each detected event, to extract the energy of the
event and the time at which is occurs, in order to test its
temporal coincidence with another event.
[0078] A device of this type carries out, for example, energy/time
conversion and encodes the events in a signal whose width is
proportional to their energy. A system of this type also permits
intrinsic encoding of the time of arrival of each event, and
therefore permits coincidence tests.
[0079] The operating principle of a system for detecting
coincidences which is based on an energy/time converter is as
follows. Two events are detected on the detectors i and j
respectively. Each energy/time converter produces a signal whose
width T is proportional to the energy imparted to the detector. If
the widths Ti and Tj correspond to the energies involved, the
events are considered to be coincident if the difference between
the start of the signal, t.sub.di-t.sub.dj, is less than the width
of the coincidence window T fixed beforehand.
[0080] FIG. 7 represents an illustrative embodiment of a circuit
320 according to the invention, which can perform energy/time
conversion of this type, and FIG. 8 represents time diagrams of the
signals taken from various points in the circuit.
[0081] The circuit in FIG. 7 comprises:
[0082] a capacitor 321 capable of integrating the signal output by
a photomultiplier 140,
[0083] an output signal detector 322 for the photomultiplier,
[0084] a delay cell 323 initiated by the aforementioned detector
322,
[0085] a current source 324 which is connected in parallel with the
capacitor 321 and is driven by the output of the delay cell
323,
[0086] a comparator 325, one input of which is grounded and the
other input of which is connected to the capacitor 321, the output
of this comparator 325 constituting the output of the energy/time
conversion device, and
[0087] a switch 326 which is controlled by the comparator 325 and
can discharge the capacitor 321.
[0088] This circuit 320 operates as follows.
[0089] The scintillation light produced by the interaction of an X
or a .gamma. photon in the Nal(Tl) crystal 130 is manifested, on
the anode of the photomultiplier 140, as a signal having a very
fast rise (in absolute value) followed by a virtually exponential
fall, typically with a time constant of the order of 230 ns. Since
the integral of this response is proportional to the energy
imparted by the radiation to the crystal, the object of the
energy/time converter 320 is to recover this integral in order to
modulate the width of a square-wave signal. The integral of the
anode signal is recovered on the capacitor 321 over a predefined
time. This time is obtained on the basis of the delay applied to
the signal extracted from the last dynode of the photomultiplier
140 (signal detection 322 and delay cell 323 modules). At the end
of the integration time, the current generator 324, which is
connected in parallel with the capacitor 321, is turned on in order
to bring about a linear discharge of this capacitor. At the same
time as the current generator 324 is started, the output of the
flip-flop 325 which gives the output signal of the converter 320
changes to a logic state "1". Wherein the voltage of the capacitor
321 passes through zero, the flip-flop 325 returns to its low
state, thus interrupting the high level of the output signal, the
current generator 324 is stopped and the capacitor 321 is
discharged fully by operating the switch
[0090] FIG. 9 illustrates an illustrative embodiment of an
acquisition circuit 330 according to the embodiment.
[0091] This circuit 330 is designed to encode energies which, for
example, range from .about.10 keV (27 keV for .sup.123I and
.sup.125I) to .about.300 keV (245 keV for .sup.111In) at a maximum
counting rate of .about.10.sup.4 hits per second per detector.
[0092] The system 330 is, for example, composed of:
[0093] a set of (for example 15) detectors (scintillator
130+photomultiplier 140),
[0094] one energy/time converter 320 coupled to each detector
110,
[0095] two detectors 331, 332, respectively for leading and
trailing edges of the signals output by the converters 320,
[0096] a clock 333 for the time base of the signals,
[0097] two timers 334, 335 driven by the clock 333,
[0098] two address counters 336, 337 driven by the edge detectors
331, 332, and
[0099] two memories 338, 339 for cyclically and temporarily storing
information then transferring it on to the bus 341 of a computer
342.
[0100] At the output of each energy/time converter 320, a signal is
found whose width is proportional to the energy imparted to the
detector 110. This width may, for example, vary from .about.10 ns
for 3 keV to .about.1 .mu.s for 300 keV. This readily permits a
counting rate of 10.sup.5 hits per second. The times of the leading
and trailing edges of the signal are calculated using the timers
334, 335 and clock 333, and are stored in the independent memories
338, 339. Once acquisition has been completed in a voxel, the data
in the memories 338, 339 are transferred to the bus 341 of the PC
in order to be processed using specific software.
[0101] Of course, the data acquisition method according to the
present invention, with a view to imaging, comprises the initial
step of injecting the body C to be analyzed with a radioactive
marker capable of emitting two coincident radiation events that are
at least slightly angularly correlated.
[0102] There are a number of possible variants for a marker of this
type.
[0103] Attention may be drawn to at least three mechanisms of
radioactive de-excitation which give rise to the emission of two
coincident photons that are only slightly angularly correlated.
[0104] In the first of the de-excitation mechanisms (isobaric
de-excitation of the nucleus), the decay of a parent nucleus
produces an excited nucleus which changes to its ground state
through a cascade, thus producing two coincident gammas. An example
of a radioelement which de-excites by this mechanism is .sup.111In.
After an electron capture, .sup.111In (half-life: 2.8 days),
changes essentially to the 417 keV excited level of .sup.111Cd. The
ground state of .sup.111Cd is reached by the cascade emission of
one gamma of 171 keV followed by another with 245 keV; the
half-life of the 245 keV level is 85 ns.
[0105] The other two mechanisms relate to radioelements whose decay
starts with electron capture, and this serves to provide the first
photon of the coincident pair. Specifically, in electron capture,
the X.sub.k emission resulting from the rearrangement of the inner
electron shells is utilized to provide a first photon. The
de-excitation of the daughter nucleus gives rise to the second
photon, and there are two possible ways that this may take place.
If the de-excitation is radiative, there will be a .gamma. photon
coincidence with the X.sub.k photon. If the de-excitation takes
place through internal conversion, there will also be electron
rearrangement and emission of an X.sub.k photon in coincidence with
that of the electron capture. Two isotopes of iodine (Z=53) give an
example of these two coincidence mechanisms: .sup.123I (half-life:
13 h) and .sup.125I (half-life: 60 days). In both cases, the
emitted X.sub.k radiation has an energy of about 27 keV, the
probability of capturing an electron in the K shell is 80% and the
fluorescence efficiency is 86%. In the case of .sup.123I, the
electron capture leads to an excited state of .sup.123Te, which
changes to the ground state by emitting a 159 keV gamma, the
X.sub.k-.gamma. coincidence factor is about 70%. In the case of
.sup.125I, the excited state of the daughter nucleus at an energy
of 35 keV, and the change to the ground state takes place either by
emission of a gamma (7% probability) or by internal conversion; the
coincidence factor for X.sub.k.gamma. plus X.sub.k-X.sub.k is
60%.
[0106] The invention is not limited to the use of the
aforementioned radioelements: .sup.123I, .sup.125I and .sup.111In,
but extends to any other equivalent radioelement which can emit at
least two temporarily coincident radiation events, for example
.gamma.-.gamma., .gamma.-X or X-X, that are at least slightly
angularly correlated.
[0107] After or before the radio tracer is injected, the body C to
be analyzed is placed in the collimating detection structure
100.
[0108] The radiation events which are emitted by the object C and
pass through the collimators 120 are detected by all the detectors
110 (scintillators 130+photomultipliers 140). The signal which is
output by the detectors 110 and has been amplified and processed in
the means 310, 320, 330 is sent to a computer 342 whose task is to
acquire and store it. The processing electronics 310, 320, 330
deliver either the signals indicating coincidence between any two
detectors 110, or a set of signals so that the coincidences which
occur can be recovered a posteriori.
[0109] The coincidence detection makes it possible to optimize the
spatial resolution and to reject signals originating from points
lying outside the focal point.
[0110] Displacing the focal point of the collimators 120 by
scanning through the volume of the region of interest during the
acquisition makes it possible to construct the image of the object
C voxel by voxel. It is thus unnecessary to use an algorithm for
reconstructing the image, which may in particular amplify the
statistical fluctuations on the reconstructed image, as in the case
of the SPECT and PET techniques, and the image may, according to
the invention, be displayed voxel by voxel as the acquisition
proceeds.
[0111] The present invention may give rise to a number of
applications which require measurement of the concentration of
radioactively marked chemical species, non-limiting examples which
may be mentioned of which applications include the in vivo
examination of small animals, in particular within the scope of
clinical research, relating for example to the detection of
cardiovascular lesions, oncology, the detection and monitoring of
tumors, studying the distribution of neuroreceptors, displaying the
functions of the brain (in the case of neurodegenerative diseases,
such as Parkinson's or Alzheimer's diseases, or Huntington's
disease; or in the event of psychiatric disorders, such as in
schizophrenia), gene therapy or, more generally, neurobiology or
neuropharmacology in order to evaluate the effectiveness of
treatments based on the administration of neuroprotective agents
and on neural grafting.
[0112] The present invention is not, of course, limited to the
particular arrangements which have just been described, but extends
to any variant in accordance with its spirit.
[0113] The use of the device and the implementation of the method
which were described above can be carried out by any authorized
individual without requiring particular knowledge in the medical
field.
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