,Mqnerlc Resonance Imaging. Vol. 4, pp. 425-429, 1986 0730-725X/86 $3.

00 + 00
Printed in the USA. All right3 reserved. Copyright 8 1986 Pergamon Journals Ltd.

l Originaf Contribution

RELAXATION TIMES IN RELATION TO GRADE OF MALIGNANCY

AND TISSUE NECROSIS IN ASTROCYTIC GLIOMAS

ELISABET ENGLUND,* ARNE BRUN,* ZOLTAN GY~RFFY-WAGNER,?

ELNA-MARIE LARSSON$ AND BERTIL PERSSON~
*Departmentsof Neuropathology, tRadiation Physics and $Diagnostic Radiology, University Hospital
Lund S-221 85, Sweden

INTRODUCTION tively. After measurements, the samples were immedi-

Highly malignant astrocytic gliomas can be demon- ately fixed in formaline and later paraffine-embedded
strated by computed tomography (CT). Low-malig- in their entirety and sectioned at 5 pm. They were
nancy astrocytomas, however, are sometimes difficult stained with hematoxylineosin and van Gieson. The
to demonstrate and even more or less impossible to samples were then studied histologically with regard
delineate precisely with available techniques. to homogeneity, malignancy grade and proportion of
In the present study, the proton magnetic reso- tissue necrosis.
nance (MR) relaxation times, Tl and T2, are cor- A total of 64 tumour biopsy specimens were ini-
related with the histopathological picture in small tially analyzed. Of this tumour material, 6 samples
biopsy samples of astrocytic gliomas. The aim is to showed low-malignancy astrocytoma (grades I-II), 32
demonstrate a possible relationship between malig- showed high malignancy (grades III-IV), and the
nancy grade and proton MR relaxation times in astro- remaining 4 samples showed intermediate-malignancy
cytomas that is consistent enough to serve as a basis astrocytoma (grades II-III) (Table 1). The remaining
for whole brain image interpretation. 22 tumour samples of varying degree of malignancy
were later, at histopathologic evaluation, excluded due
METHODS AND MATERIALS to admixture of other tissue components (normal
Tumour biopsy samples were taken directly from white matter, blood). Reference relaxation times from
neurosurgery for analysis at 37”C, in order to simu- multiple regions of normal human brain (autopsy
late in vivo conditions. Sample volume was l-5 ml. specimens), were obtained from a previous study on
Before MR measurement, a small portion of each 25 cases.’
sample was taken for water content calculations by All low- and intermediate-malignancy tumour sam-
the wet-to-dry method. A Praxis II pulsed MR- ples consisted of predominantly homogeneous tumour
analyzer was used for proton measurements at 0.25 T tissue. The material of high-malignancy gliomas was
(10.7 MHz), with the pulse sequences 90”-r-90” and divided into subgroups according to proportion of
90”~r-180”-7 for Tl and T2, respectively. The MR necrosis, which ranged from O-95% of the sectioned
signals were measured on line and stored in an Apple area (Table 1).
II computer. The curves obtained were presumed to We thus had an exact histological documentation
be monoexponential during the time interval O-900 ms of tumour tissue and a corresponding proton relaxa-
and O-30 ms after the RF-pulse for Tl and T2, respec- tion times of each sample.

Acknowledgments-The authors want to express their grati- and Swedish Cancer Society, through Grant No. 2043-
tude to Dr. Leif G. Salford and his fellow neurosurgeons B85-OIXA/85:127.
for providing us with surgical specimens. Thanks are also Address correspondence to Dr. Elisabet Englund, Central
due to Elsie Andersson and Susanne Hammarstedt for tech- Laboratory of Pathology, Department of Neuropathology
nical assistance and Elisabeth Borgstrom for manuscript University Hospital, Lund S-221 85, Sweden: Telephone
typing. This work was supported by the John and Augusta +46-46-10 34 38.
Perssons Foundation, through Grant No. 83/46 & 84156,

425
426 Magnetic Resonance Imaging 0 Volume 4, Number 5, 1986

Table 1. Astrocytoma; biopsy material, malignancy grade Tl (ms) *

.
and proportion of necrosis 1400..

.
Astrocytoma Histopathology n
1300.-
Low malignancy glioma
(grades I-II) Vital tumour, no necrosis 6
Intermediate malignancy g. 1200..
(grades II-III) ... 4
High malignancy g.
(grades III-IV) .. 9 .
llOO.-
.
. Necrosis in l-10070 3 *
.. .. ll-30% 7
.
looo~*
.. ... 31-49% 3
.. ... SO-75% 8
. . 76-95070 2 ;
900..
42 .
i
. .
.
000..
.
. .
700..
RESULTS
Both Tl and T2 values were, without exception,
T (& 0 421P)
markedly higher in all tumour groups than in normal I

I -II 11-111 Ill- IV

white matter. Mean Tl and T2 values of all non-
necrotic tumour samples were distinctly higher than
those of normal grey matter as well, although individ-
ual overlappings occurred (Table 2). TP(ms) A
.
Samples of low-malignancy astrocytomas (grades
I-II) exerted longer Tl and T2 relaxation times than
220..
did high-malignancy gliomas (grades III-IV. T2 in . .
tumour samples of intermediate malignancy (grades
II-III) fell between those of low- and high-malignancy 200..

tumours, while Tl values conformed to those of the

high-malignancy group (Fig. 1). The water content did 180..
not differ appreciably between the groups of different
malignancy grade. In highly malignant astrocytomas, ;
both Tl and T2 decreased with increasing amount of 160 ..
* .
necrosis (Fig. 2, Table 3). The shortest mean Tl and . :
T2 relaxation times in the tumour material was seen 140'.
in the high-malignancy samples with > 75% necrosis. . i
The water content did not co-vary with proportion i .
. ..
120..
of necrosis.
a .
DISCUSSION 100..

The present in vitro study was by definition per-

formed in a nonflow situation, which of course must SOY

be considered in comparing the results of different (in I ( & 0 70.7)

vivo and in vitro) studies. I- II II - III III-IV

However, Kurland, et al.* reported only slight dif-
ferences in relaxation times between an in vivo and
early postmortem stage. To ascertain the validity of
Fig. 1. (a) Tl and (b) T2 (0) in low- (I-II), intermediate-
measurements at increasing postmortal/postexcisional (II-III) and high- (III-IV) malignancy astrocytomas (entirely
time delay, we undertook a study on brain tissue from vital tumour samples). Mean values (k). Normal parietal
pig. We found that Tl values were stable and T2 val- grey (w) and white (0) matter mean values.
 MR relaxation times in relation to grade of malignancy 0 ELISABET ENGLUND ET AL. 427

Tl (ms)
1200

1100
.
i
.
1000
t :
t .
.
t * **
QOO-
t .
.
.
.
600 ..
. .
i l .
.
. . *
.
700.. .
.

1 I (10 421.4)
I
% fIecrosis 0 l-10 11-30 31-49 50-75 76 -95

(6)

T2 (ms)
160
t
.
t :
140
t t
; .
t .
120 : .

1 t
t
.. 4 2 :
100 1
9
. :
60 t
. 3
L

T ( I n 70.7)
1
% necrosis 0 l-10 11-30 31-49 50- 75 76-95

(b)

Fig. 2. (a) Tl, (b) T2 (o) and tissue necrosis in astrocytoma grades III-IV. Mean values (It). Normal parietal grey (D) and
white (0) matter mean values.

ues decreased by only 0.1 ms/h during the first 90 h concern samples of homogeneous, vital tumour tissue.
postmortem, if the samples were stored at +8”C.3 Since necrosis here lower both Tl and T2 and since
It is well known that low-malignancy astrocyto- necrosis is a regular component of high-malignancy
mas are difficult to delineate and sometimes even to astrocytomas, the differences in relaxation times be-
demonstrate with CT and other available diagnostic tween low- and high-malignancy astrocytomas would
techniques. Also on macro- and, to some extent, mi- be even greater, when the whole tumour is considered.
croscopical examination, low-malignancy gliomas may Tl for necrosis was significantly shorter than Tl
be difficult to delineate in the white matter, from for the corresponding tumour in an in vitro study on
which the tumour originates. mice.”
The present findings, however, although based on Bydder, et al.’ have reported an increase of both
a study of limited size, show that especially T2 values Tl and T2 with necrosis in tumours. However, these
of this glioma are different from those of both highly were results from a clinical study with in vivo mea-
malignant gliomas and normal brain. The differences surements, and the dissimilar results are difficult to
of Tl and T2 here mentioned (and shown in Fig. 1) compare. Hypothetically, the MR properties of vital
428 Magnetic Resonance Imaging 0 Volume 4, Number 5, 1986

Table 2. Tl and T2 values and water content in low- (I-II), intermediate- (II-III) and high- (III-IV) malignancy
astrocytomas (vital tumour samples) compared with normal (parietal) grey and white matter. Mean values f SD.

n Tl (ms) T2 (ms) HzO%

Astrocytoma I-II 6 1044.2 k 285.9 169.2 + 48.9 85.8 k 5.6

. II-III 4 919.9 t 143.6 154.0 + 42.5 86.4 + 1.8
... III-IV 9 919.8 -+ 96.3 129.8 + 15.3 82.2 + 5.9
Normal grey m. 20 767.2 k 51.6 108.6 + 8.2 84.0 t 5.6
Normal white m. 21 421.4 -t 57.4 70.7 + 12.8 68.6 -I 5.6

Table 3. Tl , T2 and tissue necrosis in high-malignancy apparent differences in mean Tl values between
astrocytomas (grades III-IV). Mean values *SD. gliomas grades I and II vs grades III and IV. Again,
these studies were designed with in vivo measurements
% necrosis n Tl (ms) T2 (ms) HzO%
and had to deal with the technical problems of e.g.
0 9 919.8 + 96.3 129.6 + 15.3 82.2 + 5.9 heterogeneity of malignancy within each tumour,
l-10 3 917.7 f 123.6 118.0 f 9.6 82.2 + 2.1 whereas the material in the present study could be
11-30 7 918.1 f 113.4 114.3 k 19.9 86.4 -t 4.9 selected according to malignancy grade. Within both
31-49 3 793.0 * 44.5 110.7 + 2.9 82.1 k 2.5 materials, there possibly were differences that were
so-75 8 778.4 k 69.9 105.1 f 12.2 82.8 k 8.4
76-95 2 749.6 * 69.2 85.3 k 3.2 81.4 f 6.8
difficult to account for, such as state of hydration/
dehydration of each patient at time of surgery.
Our findings of differences in relaxation times
between different tumour subgroups with and without
tumour and necrosis change in different ways between necrosis, and in tumour vs normal brain, were prob-
an in vivo and in vitro situation. Support for such a ably made possible through a strict control of small
speculation would lie in the fact that necrosis by defi- histologically defined samples of tumour and normal
nition is less vital than nonnecrotic tumour tissue and tissue, and the exclusion of other tissue components,
is void of the circulatory supply of the vital tissue. such as fibrohyaline scarring, blood, etc.
Future studies will hopefully clarify to what extent Tl
and T2 of tumour and/or necrosis differ between in CONCLUSION
vivo and in vitro analytic circumstances. Astrocytomas have higher Tl and T2 values than
There is a marked interindividual variability of normal grey and white matter.
relaxation times within all tumour subgroups-a find- Mean Tl and T2 values of high-malignancy as-
ing that is in accordance with the reports of other trocytomas are distinctly lower than for low-malig-
authors.5-7 This variability could not be ascribed to nancy gliomas. In high-malignancy gliomas, Tl and
varying proportions of necrosis alone, since it is obvi- T2 values decrease with increasing amount of tissue
ous mainly in the samples of grades I-II, in which necrosis.
there were no necroses. With the small sample technique and the analytic
Leviel, et ai.* report an increase of water content equipment here employed, it is possible to differenti-
in glial tumour biopsies, as compared to normal tis- ate not only between astrocytoma and normal brain
sue. If one compares the water content in tumour tissue, but also between different degrees of malig-
biopsies and normal white matter, our results are sim- nancy and proportion of tissue necrosis within the
ilar. We could not demonstrate any group-related tumour. The findings, which are based on a rigor-
variability in water content among the tumour sub- ously performed correlation of MR relaxation times
groups, but there were considerable differences within and histopathology, may prove to be of value for
each subgroup. It is known that the water content further work including image analyses.
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