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1 From the Division of Radiation Sciences, Washington University School of Medicine, St. Louis, Mo. Presented at the Sixtieth
Scientific Assembly and Annual Meeting of the Radiological Society of North America, Chicago, Ill., Dec. 1-6, 1974.
This work was supported by NIH Grant No. 5 POl HL13851, by NIH Grant 1 ROl HL15432, and by NIH Fellowship No. I-F03-
GM55196.
2 The term annihilation coincidence detection in this text denotes the simultaneous detection of the two 511 keY photons
which are created by the annihilation of a positron. ah
89
90 MICHEL :\1. TER-POGOSSI AN AND OTHERS Jan uary 197 5
Fig. 2. A. Photogra ph of pr ot ot ype PETT. The ob ject examined (phantom or a nima l ) is placed on a
turntable at the cente r of the hexagon. The turntable rotates under computer control , wit h it s axis of
rotation perpendicul ar t o t he plane of the hexagon .
B. Phantom is sho wn on th e turntable.
Nuclear
VoJ. IH POSITRON-EMMISSION TRANSAXIAL TOMOGRAPH FOR NUCLEAR IMAGING 91 Medicine
2
o~
tection with annihilation coincidence counting is ss
00
I
uu
independent of the depth of the activity in tissue. 24 1& 8 o 8 1& 24
radiation detection efficiency without loss in Fig. 4. Depth independence of annihilation coincidence de-
resolution than is possible with conventional colli- tection. The lower portion of the figure shows coincidence
mators. These characteristics of annihilation counting rate as a plane radioactive source containing a positron
emitter is moved between two detectors. If one annihilation
coincidence detection are discussed in greater de- photon traverses the thickness a to reach the detector, the other
tail below in the light of their impact on tomo- photon must traverse the thickness b and the attenuation for a
coincidence event is contributed by a + b = D.
graphic reconstruction.
Figure 3 shows the line-spread function (LSF)
and the isoresponse curves for a positron-emitting substantially with the distance between the de-
line source in water between two scintillation tector and the source. Although some degree of
detectors operated in coincidence. The full width uniformity in the isoresponse curves of single
at half maximum (FWHM) of the LSF is about photon detection can be obtained at the expense
40% of the exposed diameter of the detector of efficiency by suitably designed collimators (1,
crystals, and it does not vary significantly as a 12, 15), this method does not achieve the uni-
function of the position of the source of radiation formity of response provided by annihilation co-
between the detectors. In contrast, the resolu- incidence detection (5, 15,25,35).
tion of detectors with the typical absorbing colli- Annihilation coincidence detection permits the
mators used for single photon detection varies detection of radionuclides with sensitivity inde-
pendent of depth. As shown in Figure 4, the co-
incidence count rate remains constant as a plane
source containing a positron-emitting radionuclide
(64CU) is moved from one side of a water phantom
to the other. This is due to the fact that the two
511-keV annihilation photons must always cross a
total path length, D, to be detected in coincidence.
The absolute sensitivity can be calculated from D
and the attenuation coefficient of the material
traversed. This is not the case with single photon
detection, where sensitivity decreases with depth
due to the increasing path length through the ob-
ISQRESPONSE CURVES
PHOTO PEAK ONLY
ject and corresponding increase in attenuation.
n e t e ci c r UP/IrOlion = 53 cm Furthermore, the variation in geometrical response
of conventional absorbing collimators compounds
the difficulty in defining the spatial sensitivity.
The high energy of the annihilation radiation (511
~.~ :
keY) also minimizes variations in the attenuation
=:=.~-.-:==-=::::.==."'"
of this radiation in tissues of different composition
and thickness.
12 10 '0
-
-:r I 0.1 " .,... 0 .. -I • •) ., ., -I J J -I eJ -I et ·1 -I l
' -1 I -n 10 .,
-t
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.. '1 la-
10'
k
.. 10 '
101 110
It 10 ) 101 n o n
0 ·'
-t
-I
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•
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proach developed by the Biomedical Computer
1 • J'" I f, J. ., 101 n 1 101 .. 11 10) I U n 10' I" I U' 0 1 1 ..4 Laboratory, Washington Univ ersity School of
-I -t -t .!ufn lOO Ut I" n n"')
1011 It III 101 .. IJ n) 1 ·11 -110 .J
Medicine. The algorithm emp loyed will not be
o I I U('''(IOt I" ~)IJ' 10' 10: 10: I •• '4''''\' 1 I~l 161 12 1 • )
o I I 11 1... 1" I'" ( I'M '(No IJI 10) 101 101 101 lOt :{1_1I, 104 IU 1" U 1 " ). discussed in detail, but some of the general assump-
"---'
e) .t·t ' 111 11) 100 Ut 141 n 100 ., .. U ~. II I 101 .. I n I -11 -140 .,
tions and criteria of the mathematical reconstruc-
I " I ~ }: . ~u. ., 10' 'I lot 10\ .. 'I 10) III "I~ lot 1)0 U' Cl : ) .....
0·11 0 __
, \
' \IU {OO IU 100 'I IJ IU 10) .. 107 .. 10) 10,/1)0/ " .
I I
0 _4 •
tion used in transaxial emission tomography and
-: , ..... -4 • U. IJI n 10' U 10 1 .. 'I 104 K 10' 110 n6 UI 0 ., -1 , -a how they relate to the method of detection will be
....J " " •• } 14;') )O U. I . . . . III 10: .. 10) ucr;n~l -, -) ., ., .•
:
(I
, .) -) .1
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.J
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raphy is to reproduce the distribution of activity
1 " -, .) , 0 ·IO · J ) Cl 1 I Cl - 17 t: IJ - 10 in a cross-section slice of the body. The data for
o.n • .1
, : -I Cl I .' ....: Cl ••, • ,
recon struction are a seri es of activity profiles
obtained by performing transverse scanning at
various angles about the object in the plane of the
Fi g. 5. Numerica l printout of P ETT re constructed cross sect ion of interest. The data collected are
image from computer -simula ted data . Angu lar a nd used to generate enough ind ependent equations to
transverse sa mpling : 7.5 0 a nd I cm, re spect ively. The
simu lat ed phantom consist s of four compa rt m ent s : a recon struct the distribution of activity. On e of
L cm -thick out er rin g, a 14-cm-diamete r inner cy lind er , the primary assumptions in the reconstruction
an d t wo cy lindrica l tubes res pect ively :2.:2 an d 1.:2 cm in
di amet er , with simulat ed ac t ivit y levels of :2, 1, 4, and 4 algorithm is that th e number of counts recorded at
in each compar t ment. each point represents the sum of the activity along
In ser t : reconst ruct ed im age.
a well defined line (or region) in the plane of inter-
est . This assumption is valid for the well defin ed
and depth-independent re sponse of an annihila-
emp loyed ." As pointed out by Burnham and tion coincidence det ection system . However , the
Brownell (9) , when coincidence collimation is used, varying response with depth of single-p hoto n
all the radiation (neglect ing attenuation) can cou nt ing systems violates this assumption, pro-
theoretically be detected and its origin established. ducing a distortion of the image.
The lower sensitivity of sing le-phot on detection Although the attenuation of radiation is con-
is inherent to the loss of radiation by absorption in st ant with respect to depth on a line between two
the collimator. The efficiency of single-photon detectors in annihilation coincidence, varying
detection systems using multiple detectors in - thicknesses of materi al are interposed between
creases directly with the number of detectors, each detector pair as data are collected at different
whereas annihilation coincidence systems com- points across the ob ject . Thus an atten~ation
posed of multiple detectors can be designed to in- correction mu st be made on each data point re-
crease efficienc y by the square of the number of corded. One method is to det ermine the physical
detectors 3. Comparisons of sensit ivity of sing le dimensions of the object and multiply each data
photon and positron detection for dual probe point by e'" , where x is th e thickness of. the object
scanners (2, 25) are invalid for larger arrays of between the coincid ence detector pairs, and J.],
detectors which use such a multiple coincidenc e is an average linear attenu ation coefficient. This
design unless the above effect is con sidered . approach is subject t o error if IJ. varies significantly
R econstruction Algorithm : A number of dif- across the object, as wh en the lungs or bone are
fer ent reconstruction algorithms have been de- traversed. Another method consists of measur-
scri bed for transaxial tomographic section imagin g. ing the attenuation of 5 1l -keV radiation in the
These algorithms can be broadly classified as subject and then using this information to correct
Fourier- or non-Fourier- based. The Fourier- th e em ission data before reconstruction. W e
based algorithms (4, 10, 28, 30) use Fourier trans- have used this approach by placing a thin plastic
forms, Fourier series, convolution, or, equivalently, ring containing a solution of 64CU around the sub-
ject and collecting the count rate as a function of
J A det ailed study of the ad va nt age s of positron-emitting transverse and angular position. The same mea-
r ad ionu clides for tomographic recon st ructi on is included in "The surem ent is made without the subject in position,
a p plica t ion of annihilation coin cid en ce detecti on to transa xial
reconst ru ction tomography" by M . E . P he lps et al . (:27a ). and the ratio of the' two m easurements give s the
Nuclear
Vu!. 114 POSITRON-EMMISSION TRANSAXIAL TOMOGRAPH FOR NUCLEAR IMAGING 93 Medicine
-> ---
6 0°
.L
attenuation factor. Because of the well defined in Figures 1 and 2. The detector consists of
and depth-independent response of annihilation twenty-four 5.1 X 5.1-cm NaI(TI) scintillation
coincidence, this attenuation correction method detectors placed in a hexagonal array (4 to aside).
is accurate and simple to implement. Lead shields 2.5 cm thick with 2.5-cm diameter
The reconstruction algorithm used in this study straight-bore holes are placed in front of each
was evaluated by performing reconstructions of detector to increase the inherent detector resolu-
computer-simulated phantom data. The results tion to about 1.1 cm full width at half maximum
of such a study are shown in Figure 5. The (FWHM, Fig. 3). Shielding is provided to ex-
numerical values are in good agreement with the clude radiation originating outside the cross sec-
actual values of the activities in the cylinder and tion examined. The output of each detector is
the 2.2-cm hot tube. However, the values for connected to individual preamplifiers, amplifiers,
the I-cm thick ring and 1.2-cm hot tube of about and single-channel pulse-height analyzers. The
150 and 240 are lower than the correct values of output of the single-channel pulse-height ana-
200 and 400. This is explained by the fact that lyzers of each directly opposing pair of detec-
the sampling resolution, ring, and hot tube dimen- tors is connected to a coincidence circuit with
sions were all about 1 cm, and from the sampling a resolving time of 30 nanoseconds (Fig. 1) .
theorem the exact answer can be recovered only This establishes the "electronic" collimation of the
if the sampling resolution is S 1/2 the object size." 12 sets of detectors, since an event is accepted only
The Prototype PETT: A schematic illustration when two photons are recorded by detectors simul-
and photographs of the prototype PETT are shown taneously. With the above resolving time and
shielding, the random coincidence rate of the data
4 Experimentally, the necessary sampling resolution is usually collected in this work for the highest counting rates
from 1/2 to 1/4 the object size if quantitative recovery is to be
expected. was less than 5% of the true coincidence rate.
94 MICHEL M. TER-POGOSSIAN AND OTHERS January 1975
Relative
~_+- 2 cm 3 cm-H---..+---.I
I cm I cm
0.1 in the cylinder and the two 3-cm tubes, which transverse tomographic sections of the thorax were
is in agreement with the relative activities in the obtained at the level of the sixth thoracic vertebra
phantom. The 3-cm objects were employed to (Fig. 9). The experiment was carried out in the
demonstrate the quantitative aspect of the recon- following sequence: (a) The dog was injected
struction, since the sampling resolution (1.2 cm intravenously with 10 mCi of H 2 1;j O (1"0;
FWHM) must be 2 to 4 times smaller than the TIle = 2 min.). Three minutes was allowed for
object size (3 cm) for quantitative reconstruction. equilibration with fast equilibrating water com-
The sensitivity of the PETT for imaging pur- partments, and an image was obtained in 4.8
poses was compared to that of the scintillation minutes. (b) Twelve millicuries of 13NHs (13N;
camera. The data collection times required by the TIle = 10 min.) was injected intravenously and
two devices to obtain images of a comparable eight minutes was allowed for the clearance of the
number of counts are given in TABLE 1. Equiva- ammonia from the blood and for equilibration with
lent activities of 64CU and 99mTc were employed for soft tissues. An image was obtained in 12 min-
the PETT and scintillation camera imaging. It utes. (c) The dog was allowed to breathe llCO
should be noted that while the data were obtained (llC; Tlf, = 20 min.) for about one minute to
with a phantom filled to the top (7 cm high), the label its blood with an estimated 8 m Ci of IlCO-
PETT utilized only a cross-section slice slightly hemoglobin. Five minutes was allowed for blood
thicker than 1 cm for the formation of the image, equilibration before a 24-minute data collection
whereas the scintillation camera collected data period. (d) Ten millicuries of 18F (T If, = 110
from the whole phantom. min.) in water solution was injected, and a period
Animal Studies: 'Two sets of experiments were of one hour was allowed for the fluorine to clear
carried out in two dogs (one set per dog) to assess from thc blood. The data collection time was 24
the PETT imaging capabilities for different organs minutes.
visualized by means of pharmaceuticals labeled The images obtained in the above set of experi-
with positron-emitting radionuclides. The dogs ments were corrected for attenuation by the
were 50-lb. mongrels which were anesthetized measured transmission method described above.
throughout the duration of the experiment. For A transmission image using the data employed for
each study the dog was placed on the rotating attenuation correction is shown in Figure 9. The
table in the center of the PETT. Data were col- image obtained with H 2 1:JO shows the distribution
lected every 7.5 0 for a :3GO 0 rotation. Before each of equilibrated water in soft tissues. The equili-
measurement the previously injected activity was bratiori of water in bone is slow, which accounts
allowed to decay to a negligible level for imaging. for a void in the image at the position of the
In the first set of experiments, positron-emission vertebral column. Lungs also show a relatively
96 MICHEL M. TER-POGOSSIAN AND OTHERS January 1975
TRANSMISSI ON lie 0
low concentration of H 2 150 . The 13NH s is prefer- tion was a 4-point nearest-neighbor smoothing of
entially taken up in the myocardium, as reported a 64 X 64 data display array. No lower or upper
by others (19, 26). The contrast ratio between level suppression techniques were employed. The
the myocardium and the adjacent tissues is about displayed images represent the total reconstructed
8 to 1 in the reconstructed image. The vertebral data. The anatomical structure of the cross
column, lungs, and chambers of the heart appear sections was verified by lateral and anteroposterior
as voids in this image. The image obtained with radiographs and by autopsy performed on the
llCO-hemoglobin represents the blood distribution second dog .
in the chambers of the heart, large blood vessels
such as the aorta, and in general in the vascular DISCUSSION
distribution in surrounding tissues. The 18F is The above results show that positron-emission
mainly concentrated in the vertebral column, ribs, transaxial tomographic reconstruction permits the
and sternum. The contrast ratio in the recon- visualization of structures which are not ordinarily
structed image between the vertebral column and perceptible with conventional nuclear medicine
immediately surrounding regions is about 15 to 1. imaging devices. This result is achieved by the
In the second set of experiments, positron high contrast and uniform resolution inherent in
transverse tomographic sect ions of another dog annihilation coincidence detection and by the re-
were obtained at the level of the eleventh thoracic moval of superposition of structures through the
vertebra. The administration of H 2 150, IsNH s, use of mathematical reconstruction. These im-
and llCO-hemoglobin was carried out in the same provements are important in nuclear medicine,
manner as described above. The reconstructed where differences in image contrast determine
images are shown in Figure 10. The H 2 150 again whether or not a structure is visualized.
shows the soft-tissue distribution, whereas 13NH 3 The phantoms and animal sections imaged in
is concentrated in the liver because of the in- this study had an outer diameter which did not
corporation of the ammonia into the urea cycle. exceed 20 cm because of the limited transverse
The 11CO-hemoglobin displays the blood distribu- field size of the prototype PETT. However,
tion in large blood vessels , the liver, and the annihilation coincidence imaging can be applied
spleen. The large voids are the stomach and to considerably larger objects, because this method
small intestine. yields resolution and sensitivity independent of
The above animal studies were performed with- depth (Figs. 3 and 4). This is in contrast to single-
out phasic data collection with respect to cardiac photon imaging syste ms which generally exhibit a
cycl es or respiration. The only image manipula- decreasing resolution with depth. The attenua-
Nuclear
Vo!. 114 POSITRON-EMMISSION TRANSAXIAL TOMOGRAPH FOR NUCLEAR IMAGING 97 Medicine
tion correction of an annihilation coincidence sys- We are presently constructing an enlarged version
tem is simple and accurate. The approximate of the PETT with 8 detectors per side (48 detectors
and more complicated schemes necessary for total) and capable of providing a total number of
single photon detection systems must take into 192 pairs of detectors in coincidence. Since at
consideration the depth dependence and geo- present the sensitivity of the prototype PETT is
metrical divergence of the collimated field of view. comparable to that of a scintillation camera
These problems are aniplified for the single-photon (TABLE I), the newer device should provide a
counting system as the object size increases. tomographic imaging system considerably faster
Even if proper attenuation corrections are possible than conventional cameras presently used in
in single photon counting systems, the lower con- nuclear medicine.
trast ratio from deep-seated structures requires a The fact that the PETT can be employed only
large attenuation correction on less well defined for radionuclides decaying by positron emission
structures. The approximations used to correct may appear to limit severely the possible clinical
for these factors, or ignoring them, results in a usefulness of this approach. However, there are
distortion of the image in single-photon counting a number of positron-emitting radionuclides with
systems. The degree of such distortion and its physical and chemical characteristics very favor-
significance in reconstructed images have not yet able for use in nuclear medicine. For example,
been fully investigated. 68Ga (Tlj, = 68 min.) is produced by a long-lived
The positron emission transverse tomograph generator, 68Ge (Tlj, = 272 days), and is a posi-
can be designed to utilize the radiation emitted tron-emitting analog of 67Ga, the usefulness of
by radionuclides more efficiently than is generally which is well recognized in nuclear medicine.
possible with single photon detection systems. In addition, a number of nuclides (e.g., lIe, 150,
The prototype PETT described in this work em- 13N, 18F) currently employed in physiological
ploys only coincidences occurring in directly studies are positron-emitters. In general, the
opposing pairs of detectors. However, as pre- dedication of this apparatus to the use of positron-
viously discussed, a much more efficient utilization emitting radionuclides may be less restrictive than
of the annihilation radiation is accomplished by the limitations imposed on scintillation cameras,
the use of a multiple coincidence logic. The which require low-energy photon-emitters, or
multiple coincidence logic for the PETT utilizes those imposed by the chemical properties of tech-
coincidences between each detector on one side of netium.
the hexagon with all the detectors on the opposing It is our opinion that the use of a transaxial
side. Thus where the directly opposing coin- tomographic system for the imaging of organs and
cidence logic uses 12 pairs of coincident detectors, structures containing positron-emitting radio-
the multiple coincidence has a total of 48, an im- nuclides opens fruitful new areas of exploration
provement in efficiency by about a factor of 4. in nuclear medicine by removing some of the
98 MrCHEL M. TER-POGOSSrAN AND OTHERS January 1975
restrictive barriers imposed by present-day tech- scan resolution without sensitivity loss: "Constant resolution"
collimator. [In] Medical Radioisotope Scintigraphy, Vo!. 1.
niques, instrumentation, and limited choice of Vienna, IAEA, 1968, pp .'561-574
radionuc1ides. 16. Gilbert PF: The reconstruction of a three-dimensional
structure from projections and its application to electron micros-
copy. H. Direct methods. Proc R Soc Lond [BioI] 182:
ACKNOWLEDGMENTS: Our thanks are due to Dr. J. R. 89-102, 25 Jul 1972
Cox and Dr. Donald Snyder for algorithms and discussion, 17. Gordon R, Bender R, Herman GT: Algebraic recon-
struction techniques (ART) for three-dimensional electron
to Dr. Henry Huang for simulation and discussions, to Dr. microscopy and x-ray photography. J Theor BioI 29:471-481,
Barry Siegel and Dr. R. E. Coleman for animal preparation Dec 1970
and helpful discussions, to Mr. Julius Hecht for technical 18. Cordon R, Herman C: Reconstruction of pictures from
assistance, and to Ms. Carol Coble for computer program- their projections. Comm ACM 14: 759, 1971
19. Harper PV, Lathrop KA, Krizek H, et al: Clinical
ming. feasibility of myocardial imaging with r3NH3 • J Nucl Med 13:
278-280, Apr 1972
Division of Radiation Sciences 20. Kuhl D: Section scanning. [In] Proc Syrnp Soc Nucl
Mallinckrodt Institute of Radiology Med, New York, 1972. In press
Washington University School of Medicine 21. Kuhl DE, Edwards RQ: Image separation radioisotope
510 South Kingshighway scanning. Radiology 80:653-661, Apr 1963
St. Louis, Mo. 63110 22. Kuhl DE, Edwards RQ: Reorganizing data from trans-
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