Diffusion-weighted magnetic resonance imaging in non-invasive monitoring of antiangiogenic therapy in experimental tumor model
Aim: To show usefulness of diffusion-weighted magnetic resonance imaging (MRI) for non-invasive assessment of experimental tumor after antiangiogenic treatment. Methods: M1 sarcoma was implanted to the peritoneal cavity of the rat and allowed to grow to a palpable tumor size. Animal was treated with...
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| Опубліковано в: : | Experimental Oncology |
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| Дата: | 2010 |
| Автори: | , , |
| Формат: | Стаття |
| Мова: | Англійська |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2010
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| Назва журналу: | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| Цитувати: | Diffusion-weighted magnetic resonance imaging in non-invasive monitoring of antiangiogenic therapy in experimental tumor model / S.A. Kharuzhyk, N.A. Petrovskaya, M.A. Vosmitel // Experimental Oncology. — 2010. — Т. 32, № 2. — С. 104-106. — Бібліогр.: 7 назв. — англ. |
Репозитарії
Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1860269217639563264 |
|---|---|
| author | Kharuzhyk, S.A. Petrovskaya, N.A. Vosmitel, M.A. |
| author_facet | Kharuzhyk, S.A. Petrovskaya, N.A. Vosmitel, M.A. |
| citation_txt | Diffusion-weighted magnetic resonance imaging in non-invasive monitoring of antiangiogenic therapy in experimental tumor model / S.A. Kharuzhyk, N.A. Petrovskaya, M.A. Vosmitel // Experimental Oncology. — 2010. — Т. 32, № 2. — С. 104-106. — Бібліогр.: 7 назв. — англ. |
| collection | DSpace DC |
| container_title | Experimental Oncology |
| description | Aim: To show usefulness of diffusion-weighted magnetic resonance imaging (MRI) for non-invasive assessment of experimental tumor after antiangiogenic treatment. Methods: M1 sarcoma was implanted to the peritoneal cavity of the rat and allowed to grow to a palpable tumor size. Animal was treated with a single injection of endothelial growth factor antibody Bevacizumab (Avastin). Serial MRI scanning including diffusion-weighted sequence was performed before and up to 100 h after treatment. Animal was sacrificed thereafter and MRI data were correlated with morphology. Results: Apparent diffusion coefficient (ADC) maps derived tumor necrotic area correlated well with histology-derived tumor necrotic area. ADC threshold of 1.39 × 10–3 mm2/s appeared to be optimal for tumor necrosis quantification in this tumor model and allowed to follow temporal changes of tumor internal structure after treatment. Conclusion: Diffusion-weighted MRI permits non-invasive tissue characterization without the need for exogenous contrast agents and, therefore, may be used to individualise therapy and to monitor tumor response.
|
| first_indexed | 2025-12-07T19:04:56Z |
| format | Article |
| fulltext |
104 Experimental Oncology 32, 104–106, 2010 (June)
Magnetic resonance imaging (MRI) is widely used
in diagnostics of malignant tumors and evaluation
of anticancer treatment efficacy bough in human and
experimental models. T2- and T1-weighted images
are routinely applied, providing information about size
and internal structure of tumor, its relationship with sur-
rounding tissues, the presence and severi ty of contrast
enhancement. In addition to these anatomical MRI
techniques, so called “functional” sequences has been
developed in recent years. In functional MRI unique
pathophysiological features of tissues are used for
creation of images such as blood flow changes (ische-
mia, angiogenesis) in perfusion MRI and changes
in the cellular composition (hypercellularity, necrosis)
in diffusion-weighted MRI (DWI).
Initially DWI has been applied for early diagnos-
tics of brain ischemia [1]. Cytotoxic edema develops
immediately after blood flow shut down in the af-
fected region of the brain. It characterized by fluid
flow into intracellular space followed by cells swelling
and decreasing of free mobility of water molecules
in the constricted extracellular space. These areas
with decreased water diffusion have altered signal
on diffusion-weighted images, allowing to identify
ischemia several hours earlier than on T2-weighted
images. In recent years, it has been found that solid
tumors are also characterized by decreased diffusion
as they usually have increased cellular density. In op-
posite, areas of necrosis have increased diffusion due
to absence of cell membranes as barriers for mobility
of water molecules [2].
DWI has been used to detect tumors [3], to dif-
ferentiate benign from malignant tumor types [4],
and to detect diffusion changes after tumor therapy
in human [5] and animal models [2, 6]. For assess-
ment of antiangiogenic drugs therapies, DWI offers an
attractive alternative to anatomic size measurements
and/or histopathology because changes in size may
not correlate with therapeutic efficacy, size changes
may occur with significant delay relative to functional
changes in tumor physiology and the invasive nat ure
of histopathology complicates longitudinal studies. An
important advantage of DWI is the possibility of quanti-
tative assessment by constructing map of the apparent
diffusion coefficient (ADC map). In the present work we
demonstrate use of DWI for non-invasive assessment
of tumor internal structure changes in experimental
model of peritoneal carcinomatosis treated with anti-
angiogenic drug Avastin with morphologic correlation.
Tumor model. Animal experiments were conducted
in compliance with all ethical and legal requirements.
An experimental animal, a white rat, was obtained from
the vivarium of the N.N. Alexandrov National Cancer
Center of Belarus. M-1 sarcoma, a transplantable rat
tumor, was used in the experiments. The strain was
obtained from the Oncology Research Centre of the
Russian Academy of Medical Sciences and was passed
by serial transplantation. Tumor nodes were isolated
and homogenized, then Hank’s solution was added to
yield 10% suspension. The tumor cell suspension was
injected under the capsule of the peritoneal surface
in the left lower side of the abdomen.
MRI scanning and treatment. Baseline MRI scan
was performed under general anesthesia 19 days
after tumor transplantation and consisted of coronal
and transversal T2- and T1-weighted images followed
by DWI in transversal plane. Positions and thickness
(3 mm) of DWI slices were copied from transversal
T2-weighted images which served as anatomic refe-
rence. Four central tumor slices were underwent future
quantitative analysis in correlation with histology.
DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING
IN NON-INVASIVE MONITORING OF ANTIANGIOGENIC THERAPY
IN E XPERIMENTAL TUMOR MODEL
S.A. Kharuzhyk1, *, N.A. Petrovskaya2, M.A. Vosmitel3
1Department of Diagnostic Radiology, 2Department of Hyperthermia and Photodynamic Therapy, 3Department
of Pathology, N.N. Alexandrov National Cancer Center of Belarus, BY 223040 Lesnoj 2, Minsk, Belarus
Aim: To show usefulness of diffusion-weighted magnetic resonance imaging (MRI) for non-invasive assessment of experimental
tumor after antiangiogenic treatment. Methods: M1 sarcoma was implanted to the peritoneal cavity of the rat and allowed to grow
to a palpable tumor size. Animal was treated with a single injection of endothelial growth factor antibody Bevacizumab (Avastin).
Serial MRI scanning including diffusion-weighted sequence was performed before and up to 100 h after treatment. Animal was
sacrificed thereafter and MRI data were correlated with morphology. Results: Apparent diffusion coefficient (ADC) maps derived
tumor necrotic area correlated well with histology-derived tumor necrotic area. ADC threshold of 1.39 × 10–3 mm2/s appeared to be
optimal for tumor necrosis quantification in this tumor model and allowed to follow temporal changes of tumor internal structure
after treatment. Conclusion: Diffusion-weighted MRI permits non-invasive tissue characterization without the need for exogenous
contrast agents and, therefore, may be used to individualise therapy and to monitor tumor response.
Key Words: diffusion-weighted magnetic resonance imaging, peritoneal carcinomatosis, antiangiogenic therapy, non-invasive assessment.
Received: May 11, 2010.
*Correspondence: E-mail: skharuzhyk@nld.by
Abbreviations used: ADC — apparent diffusion coefficient; DWI —
diffusion-weighted imaging; MRI — magnetic resonance imaging;
SSD — sum of square differences.
Exp Oncol 2010
32, 2, 104–106
SHORT COMMUNICATIONS
Experimental Oncology 32, 104–106, 2010 (June) 105
Immediately after MRI Bevacizumab (Avastin)
endothelial growth factor antibody (Genentech Inc.,
South San Francisco, CA) was injected in tail vein in
dose 15 mg/kg. Animal was undergone to MRI for
noninvasive monitoring at 24, 48, 80 and 100 h after
single dose Avastin injection using the same scanning
protocol as described above.
Morphology examination. To validate the data of
MRI animal was sacrificed after last MRI examination
(according to the regulations of local Ethic Committee).
At necropsy, the tumor was removed and fixed in 10%
neutral buffered formalin for over 24 h. Four transversal
parallel 3 mm thick sections were obtained through
center of the tumor in correspondence to transversal
DWI and T2-weighted images of MRI. H&E staining was
done using standard protocols of histology investigation.
Regions of necrosis were demarcated on the digital photo
of the histology sections and percentage of necrotic
tumor area was calculated for each section.
ADC maps analysis. ADC maps were recon-
structed from DWI series using scanner software.
Diffusion-weighted images and ADC maps have lower
spatial resolution and, thus, are interpreted together
with Т2- and Т1-weighted images, which serve as
anatomic reference. On the ADC map signal intensity
of each pixel corresponds to the diffusion coefficient
at this point. Necrotic areas which are characterized
by increased diffusion have increased signal (appears
white) while solid tumor parts look dark. To analyze ADC
maps quantitatively ImageJ program (NIH, Bethesda,
USA) was used. Tumor node was contoured and ADC
threshold was found for which the total area of pixels
in each slice with the intensity of the signal above the
threshold value (ADC-derived tumor necrotic area)
best suited to the area of necrosis in corresponding
morphology slice (histology-derived tumor necrotic
area). Sum of square differences (SSD) technique
was used to find an optimal threshold [7]. The optimal
threshold value was determined as that which yield the
minimum SSD between ADC- and histology-derived
tumor necrotic areas on four analyzed tumor slices. As
shown in Fig. 1 minimum SSD was obtained with ADC
threshold of 1.39 × 10–3 mm2/s. Fig. 2 shows correlation
plots of ADC- and histology-derived tumor necrotic
areas estimated using representative ADC thresholds
of 1.35, 1.39 and 1.41 × 10–3 mm2/s relative to the model
x = y line. Threshold of 1.35 × 10–3 mm2/s overestimates
tumor necrosis compared to histology while threshold
of 1.41 × 10–3 mm2/s underestimates it. Using optimal
ADC threshold of 1.39 × 10–3 mm2/s, percentage of
ADC-derived tumor necrotic area on each of four
slices was 21.1, 16.4, 15.7 and 28.8%, showing excel-
lent correspondence to 21.1, 18.6, 15.9 and 28.6% on
histology respectively. MRI and pathology images from
representative tumor slice are shown on Fig. 3.
ADC maps analysis allowed to follow temporal
changes of tumor internal structure after treatment.
ADC-derived tumor necrotic volume increased gradu-
ally from 6.7% before treatment to 11.6% at 48 h and
up to 27.7% at 80 h after Avastin injection.
0
5
10
15
20
25
30
1.34 1.35 1.36 1.37 1.38 1.39 1.4 1.41 1.42
ADC treshold (x 10–3 mm2/s)
SS
D
(a
rb
. u
ni
ts
)
Fig. 1. Plot of sum of square differences (SSD) of ADC- and
histology-derived tumor necrotic areas on four slices versus ADC
threshold. Minimal SSD value was achieved with ADC threshold of
1.39 × 10–3 mm2/s indicating best correspondence of ADC- and
histology derived tumor necrotic areas
0
5
10
15
20
25
30
35
40
0 5 10 15 20 25 30 35 40
1.
35
x
1
0–3
m
m
2 /s
A
DC
tr
es
ho
ld
0
5
10
15
20
25
30
35
40
0 5 10 15 20 25 30 35 40
1.
39
x
1
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m
m
2 /s
A
DC
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es
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1.
41
x
1
0–3
m
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A
DC
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es
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0
5
10
15
20
25
30
35
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0 5 10 15 20 25 30 35 40
AD
C-
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ed
tu
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or
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tic
a
re
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%
Histology-derived tumor necrotic area, %
a
b
c
Fig. 2. Correlation plots between ADC- and histology-derived tumor
necrotic areas relative to the model x = y line. Every point on the plot
corresponds to individual tumor slice. Representative ADC thre-
sholds of (a) 1.35, (b) 1.39 and (c) 1.41 × 10–3 mm2/s are shown. The
best correspondence of ADC-derived and histology-derived tumor
necrotic areas is achieved with ADC threshold of 1.39 × 10–3 mm2/s
106 Experimental Oncology 32, 104–106, 2010 (June)
In conclusion, DWI uses local water mobility as
an endogenous probe for noninvasive interrogation
of tissue microstructure and may permit tissue cha-
racterization without the need for exogenous contrast
agents. It offers non-invasive evaluation of tumor
necrotic fraction before, during and after treatment
and, therefore, may be used to individualise therapy
and to monitor tumor response.
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weighted magnetic resonance imaging in the early detection
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Copyright © Experimental Oncology, 2010
a b
c d
Fig. 3. MRI (a–c) and histology (d) images from representative slice of M1-sarcoma at 100 h post treatment with Avastin: (a) T2-weighted
image and (b) ADC map of the experimental animal whole body transversal cross-section; (c) ADC map and (d) H&E stained section
of evaluated tumor node which is delineated on (b). Red pixels on (c) represent ADC values above 1.39 × 10–3 mm2/s threshold which
appeared optimal for discrimination of solid and necrotic areas on this tumor model. White areas in the tumor on (b) and red pixels
on (c) excellently match necrotic areas in the H&E stained section (arrows on (d)) as opposed to T2-weigted image on which tumor
necrosis is not easily appreciated
|
| id | nasplib_isofts_kiev_ua-123456789-138599 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 1812-9269 |
| language | English |
| last_indexed | 2025-12-07T19:04:56Z |
| publishDate | 2010 |
| publisher | Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| record_format | dspace |
| spelling | Kharuzhyk, S.A. Petrovskaya, N.A. Vosmitel, M.A. 2018-06-19T10:20:31Z 2018-06-19T10:20:31Z 2010 Diffusion-weighted magnetic resonance imaging in non-invasive monitoring of antiangiogenic therapy in experimental tumor model / S.A. Kharuzhyk, N.A. Petrovskaya, M.A. Vosmitel // Experimental Oncology. — 2010. — Т. 32, № 2. — С. 104-106. — Бібліогр.: 7 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/138599 Aim: To show usefulness of diffusion-weighted magnetic resonance imaging (MRI) for non-invasive assessment of experimental tumor after antiangiogenic treatment. Methods: M1 sarcoma was implanted to the peritoneal cavity of the rat and allowed to grow to a palpable tumor size. Animal was treated with a single injection of endothelial growth factor antibody Bevacizumab (Avastin). Serial MRI scanning including diffusion-weighted sequence was performed before and up to 100 h after treatment. Animal was sacrificed thereafter and MRI data were correlated with morphology. Results: Apparent diffusion coefficient (ADC) maps derived tumor necrotic area correlated well with histology-derived tumor necrotic area. ADC threshold of 1.39 × 10–3 mm2/s appeared to be optimal for tumor necrosis quantification in this tumor model and allowed to follow temporal changes of tumor internal structure after treatment. Conclusion: Diffusion-weighted MRI permits non-invasive tissue characterization without the need for exogenous contrast agents and, therefore, may be used to individualise therapy and to monitor tumor response. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Short communications Diffusion-weighted magnetic resonance imaging in non-invasive monitoring of antiangiogenic therapy in experimental tumor model Article published earlier |
| spellingShingle | Diffusion-weighted magnetic resonance imaging in non-invasive monitoring of antiangiogenic therapy in experimental tumor model Kharuzhyk, S.A. Petrovskaya, N.A. Vosmitel, M.A. Short communications |
| title | Diffusion-weighted magnetic resonance imaging in non-invasive monitoring of antiangiogenic therapy in experimental tumor model |
| title_full | Diffusion-weighted magnetic resonance imaging in non-invasive monitoring of antiangiogenic therapy in experimental tumor model |
| title_fullStr | Diffusion-weighted magnetic resonance imaging in non-invasive monitoring of antiangiogenic therapy in experimental tumor model |
| title_full_unstemmed | Diffusion-weighted magnetic resonance imaging in non-invasive monitoring of antiangiogenic therapy in experimental tumor model |
| title_short | Diffusion-weighted magnetic resonance imaging in non-invasive monitoring of antiangiogenic therapy in experimental tumor model |
| title_sort | diffusion-weighted magnetic resonance imaging in non-invasive monitoring of antiangiogenic therapy in experimental tumor model |
| topic | Short communications |
| topic_facet | Short communications |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/138599 |
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