Diagnostic and Interventional Imaging (2018) 99, 473—481

ORIGINAL ARTICLE /Cancer imaging

Perfusion MR imaging at 3-Tesla: Can it

predict tumor grade and histologic necrosis
rate of musculoskeletal sarcoma?
P.A. Gondim Teixeira a,∗, A. Renaud b, S. Aubert c,
M. Ben Haj Amor b, Y.-M. Robin d, A. Cotten e,
L. Ceugnart b

a
Department of Imaging, hôpital Central, CHRU de Nancy, 29, avenue du
Maréchal-Lattre-de-Tassigny, 54035 Nancy, France
b
Medical Imaging Department, Oscar Lambret Center, Lille Nord University, 3, rue
Frédéric-Combemale, 59000 Lille, France
c
Department of Pathology, University Hospital CHRU, University Lille-Nord de France, 59000
Lille, France
d
Department of General Oncology, Oscar Lambret Cancer Center, 59000 Lille, France
e
Centre de consultation et d’imagerie de l’appareil locomoteur (CCIAL), CHRU de Lille, 2,
avenue Oscar-Lambret, 59037 Lille cedex France

KEYWORDS Abstract
Magnetic resonance Purpose: To identify quantitative perfusion parameters that are best associated with tumor
imaging (MRI); grade and tumor necrosis at magnetic resonance (MR) imaging at 3-Tesla.
Perfusion MR Methods: MR perfusion studies of 31 patients with a musculoskeletal sarcoma were retrospec-
imaging; tively evaluated by two readers. There were 18 men and 13 women with a mean age of
Musculoskeletal 34.9 ± 24.4 (standard deviation [SD] years) (range: 6—87 years). All patients underwent car-
sarcoma; cinologic tumor resection less than 3 months after MR imaging. For all patients six perfusion
Neoplasm grading; parameters (three semi-quantitative and three permeability parameters) were analyzed. The
Tumor necrosis percentage of tumor necrosis was estimated using MR imaging. Perfusion data were compared
between groups of tumors with different grades and necrosis ratios. Interobserver variability
was calculated using intraclass correlation coefficient (ICC).

Abbreviations: FNCLCC, Fédération nationale des centres de lutte contre le cancer; MSK, Musculoskeletal system; INI, Imaging necrosis
index; ROI, Region of interest; FSE, Weighted fast spin-echo; NEX, Number of excitations; FOV, Field of view; HPF, High power field; SPGR,
Spoiled gradient-echo; AIF, Arterial input function; ICC, Intraclass correlation coefficients; EES, Extravascular extracellular space; CER,
Contrast enhancement ratio; AUC, Area under the curve; Max Slope, Maximum slope of increase; Ktrans , Transfer constant from the plasma
to the extravascular extracellular space; kep , Backflux constant; Ve , Extravascular extracellular space volume.
∗ Corresponding author.

E-mail address: ped gt@hotmail.com (P.A. Gondim Teixeira).

https://doi.org/10.1016/j.diii.2018.02.005
2211-5684/© 2018 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.
474 P.A. Gondim Teixeira et al.

Results: Interobserver variability among the perfusion parameters was good to excellent (ICC:
0.72—0.9). The area under the curve and maximum slope values showed a significant association
with the degree of tumor necrosis (P = 0.02—0.04). When tumors with low necrosis ratios were
compared to those with high ratios the former parameter was 80% lower. In the same groups,
the imaging necrosis index was 56.9—59.8% higher in patients with grade 2 necrosis (P = 0.01).
Extracellular space volume (Ve ) was 31.4% to 55.8% lower in tumors with high grade while the
backflow constant (Kep ) was 33.6% to 40.1%% higher in tumors with high grade.
Conclusion: Semi-quantitative MR perfusion parameters have an excellent reproducibility and
are associated with the degree of histologic tumor necrosis in musculoskeletal sarcomas. The
utility of permeability parameters for determining tumor grade needs further investigations.
© 2018 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Introduction which increase the discrepancies between imaging and his-

Tumor histological grading is an important prognostic factor
for patients with musculoskeletal sarcomas and is related
to the likehood of metastatic disease and overall sur-
vival [1—4]. Studies have suggested an association between
tumor grade and surgical margin status, which is another
strong prognostic indicator [3]. Treatment-induced histolog-
ical necrosis is reported to be an independent predictor
of overall survival and recurrence rates in patients with
high grade soft-tissue sarcomas [5—8]. Tumor grading is
more accurately performed on a whole tumor or surgical
biopsy specimens [9]. Grading based on core biopsy mate-
rial remains controversial due to tumor sampling issues and
difficulties in evaluating tumor necrosis and mitotic indexes
[1].
Magnetic resonance (MR) imaging obtained after intra-
venous administration of a gadolinium chelate is currently
used for musculoskeletal tumor characterization, local
staging and post-treatment follow-up [10—13]. Contrast-
enhanced MR perfusion can non-invasively help assess tumor
capillary density and vessel permeability [14,15]. Perfusion
characteristics of viable and necrotic tumors areas are fairly
different, making necrotic tissue assessment possible with
this technique [16]. Although MR perfusion parameters have
been shown to be associated with tumor grading in brain
gliomas and liver tumors, there is scarce information regard-
ing the correlation with tumor grade in musculoskeletal
sarcomas [17,18]. Non-invasive tumor grading may help opti-
mize patient imaging evaluation, surgical planning and the
evaluation of treatment response.
Musculoskeletal sarcomas are frequently heterogeneous
tumors with different zones of viable and necrotic tissue,
which makes imaging post-processing difficult, most notably
for selecting regions of interest (ROI) for analysis. Moreover,
post-processing and measurements in MR imaging tend to be
performed in the original acquisition plane for simplicity and
to avoid reconstruction-related image quality loss. While
there are no guidelines to determine the perfusion acquisi-
tion plane, macroscopic histopathological sectioning (which
determines the zones to be evaluated microscopically) is
performed by convention in the largest tumor diameter,
tologic analysis [19].
The objective of this study was to identify quantitative
perfusion parameters that are best associated with tumor
grade and tumor necrosis at MR imaging.
Materials and methods
Patients
The medical and imaging files of 74 patients, who underwent
MR imaging in our institution from May 2014 to January 2017
for the evaluation of bone or soft-tissue tumors, were ini-
tially retrospectively evaluated. A total of 43 patients with a
tumor other than sarcoma or who underwent surgical resec-
tion of their tumor more than three months after MR imaging
were excluded.
The study population consisted of 31 patients with a
histopathologically proven sarcoma who underwent curative
surgical resection less than three months after MR imag-
ing. There were 18 men and 13 women with a mean age
of 34.9 ± 24.4 (standard deviation [SD] years) (range: 6—87
years). At the time of MR imaging, nine patients presented
with native tumors not being treated, 18 patients were
under chemotherapy and four patients had received radio-
therapy. Due to the retrospective data analysis, institutional
review board exemption was granted.
Pathological analysis
The surgical specimens of all tumors were analyzed by a
pathologist specialized in musculoskeletal tumors. At least
one section per centimeter in the plane of the largest tumor
diameter was performed considering tumor heterogeneity
along with surgical margins sampling according to interna-
tional recommendations [19]. Soft-tissue tumor grading was
performed according to the French system of the Cancer
Centers (Fédération nationale des centres de lutte contre le
cancer [FNCLCC]) while the grading of bone sarcomas was
performed according to Broder’s system [5,19]. The follow-
ing parameters were extracted from these reports:
Perfusion MR imaging in musculoskeletal sarcomas
• tumor grade: grades 1 and 2 of the FNCLCC or Broder’s
systems were considered to be low grade whereas FNCLCC
grade 3 tumors and Broder’s grade 3 or 4 tumors were
considered to be high grade;
• tumor differentiation: score 1 = sarcomas closely
resembling normal adult mesenchymal tissue; score
2 = sarcomas for which histologic typing is certain; score
3 = embryonal and undifferentiated sarcomas, sarco-
mas of doubtful type, synovial sarcomas, soft-tissue
osteosarcomas, primitive neuroectodermal tumors;
• necrotic index: score 0 = no necrosis; score 1 = less than
50% tumor necrosis; score 2 ≥ 50% necrosis. Tumors scored
0 and 1 were considered to have a low necrosis ratio
whereas those scored 2 were considered to have a high
necrosis ratio;
• mitotic index. Score 1 = 0—9 mitoses per 10 high power
fields (HPF); score 2 = 10—19 mitoses per 10 HPF; score
3 ≥ 20 mitoses per 10 HPF.
MR image acquisition
®
Images were acquired with a 3T MR scanner (Discovery
MR750W, General-Electric Healthcare, Milwaukee, WI, USA).
Coils were adapted to tumor location. The acquisition proto-
col included conventional a T1-weighted fast spin-echo (FSE)
sequence, a T2-weighted FSE fat-saturated sequence in at
least two different orthogonal planes and a T1-weighted FSE
fat-saturated sequence post gadolinium.
A three-dimensional (3D) spoiled gradient-echo (SPGR)
sequence was used to evaluate tissue perfusion (TE = 2 ms;
TR = 3.8; flip angle = 30◦ , bandwidth = 50 Hz; NEX = 0.5, accel-
eration factor 2.5; matrix from 128 × 128 to 160 × 160;
FOV 320 mm; slice thickness 3.4—5 mm); 28 volumes were
acquired in 3.2 minutes yielding a temporal resolution of 7
s. In total, 0.2 mL/kg of gadolinium-based contrast material
®
(gadoterate meglumine, Dotarem at a dose of 0.5 mmol/ml
Guerbet, Roissy CdG, France) was injected into a periph-
eral vein. An injection pump (Mallinckrodt, OptistarTM Elite,
Guerbet, Bloomington, IN, USA) was used for all injections.
The injection rate was adapted to the patient’s age and
peripheral vein status and varied from 1 mL/s to 5 mL/s
(mean = 3.3 ± 1.1 [SD] mL/s). The delay between the start of
image acquisition and gadolinium injection was 21 seconds.
Perfusion parameters calculation
Image post-processing was performed using the AD Volume
Share 5 (V.4.6, GE Healthcare) using the GenIQ and the
Readyview modules. The arterial input function (AIF) was
calculated semi-automatically by placing an ROI over vessels
adjacent to the tumor.
Two types of perfusion parameters were acquired:
semi-quantitative and permeability. The following semi-
quantitative parameters were calculated: the contrast
enhancement ratio (CER) (peak signal—baseline sig-
nal/baseline signal), the area under the curve (AUC) and
the maximum slope of increase defined as the curve slope
of the steepest part of the curve. A fixed T1 value (900 ms),
as reported by Bazelaire et al. obtained with similar equip-
ment, was used for permeability parameter calculations
[15]. Permeability parameters were calculated using the
475
extended Tofts pharmacokinetic model with the following
equation [20]:
 t
Ct (t) = vp Cp (t) + K trans Cp () e−kep (t−) d
0
Application of this pharmacokinetic model yielded three
quantitative perfusion parameters: the volume transfer
constant from the plasma to the extravascular extracellu-
lar space (EES) (Ktrans in min —1), the rate constant of the
backflux from the EES to the plasma (kep in min —1) and the
EES volume (Ve ).
Slice selection and region of interest (ROI)
positioning
Two radiologists, both with 10 years of clinical experience
with MR imaging, post-processed MR perfusion studies inde-
pendently. The readers were blinded for tumor histologic
characteristics. Slice selection and ROI positioning was per-
formed on perfusion images. The orthogonal plane and the
slice demonstrating the largest tumor diameter was selected
for analysis. Three ROI were positioned according to the
following procedures (Fig. 1):
• global tumor ROI: an elliptical ROI was positioned to
occupy the largest tumor diameter, including areas of
viable and necrotic tumor. The association between per-
fusion parameters derived from this ROI and histologic
tumor grade and necrosis was evaluated;
• normal appearing muscle ROI: an elliptical ROI was
positioned over normal appearing (intermediate signal
intensity in both T1- and T2-weighted sequences) striated
muscle in the study region. Intra-muscular vessels were
avoided. Normal muscle perfusion data were acquired to
allow for the calculation of tumor/normal muscle ratios
used to avoid the influence of technical factors (different
coils, signal gain, coil filling rate and variable injection
rates);
• viable tumor ROI: a free-form ROI was drawn over the
viable tumor area. Viable tumor was defined as enhancing
areas in the perfusion study. All phases of the perfu-
sion acquisition were considered when determining viable
tumor. Small foci of necrosis completely surrounded by
viable tumor were not considered in the determination
of viable tumor zones. This ROI was used to allow the
calculation of the INI.
The areas in mm2 of viable and global tumor ROI were
used to calculate the percentage of tumor necrosis on imag-
ing, designated as imaging necrotic index (INI). Negative
INI values were considered to represent 0% necrosis. Post-
processing time varied from 10 to 15 minutes.
Statistical analysis
Statistical analysis was performed with the Stata software
(v.11.2 Statcorp. 2009). Tumor/normal muscle ratios of
all perfusion parameters acquired were considered. Uni-
variate logistic regression analysis was used to assess the
relationship between perfusion parameters and histological
variables (tumor grade and necrosis rate). Intraclass correla-
tion coefficients (ICC) of the perfusion parameters obtained
476 P.A. Gondim Teixeira et al.

Figure 1. An 18-year-old man with osteosarcoma of the proximal fibula. A. Axial post-contrast T1-weighted fat-saturated image demon-
strates an aggressive lesion centered on the proximal fibula (arrowheads) with a necrotic center (area delimitated by the dashed line) and
surrounded by a halo of soft-tissue edema. B. Macroscopic section of the surgical specimen in the sagittal plane of this lesion shows areas of
necrosis (whitish central zone) and viable tissue (peripheral pinkish zone). C—E. ROI positioning procedure. C. A coronal oblique perfusion
image demonstrates the largest tumor diameter is selected. D. A free-form ROI (viable tumor ROI) was drawn to include the largest area
possible of enhancing tumor (red free-form). Small foci of necrosis completely surrounded by viable tumor were not considered in the
analysis (thin arrow). E. An elliptical ROI was drawn to include the largest tumor diameter possible (global tumor ROI) (blue elliptical ROI).

by the two readers were calculated. ICC values less than
0.40 were considered as poor agreement, 0.40—0.59 as fair,
0.60—0.74 as good, and 0.75—1 was accepted as excellent
agreement. Quantitative variables were expressed as mean
SD and range. Statistical significance threshold was set at
P < 0.05.
Results
The mean delay between MR examination and histologic
analysis was 21.8 ± 17.9 (SD) days (range: 2—70 days). The
histologic subtypes and grading of the tumors included are
presented in Table 1. Perfusion analysis was successful in
all patients. The ICC values of the perfusion parameters
acquired varied from 0.72 to 0.9 and were considered good
to excellent. The relation between mean values, SD and vari-
ation percentage of the perfusion parameters with respect
to tumor grade and necrosis rate are reported in Table 2.
Perfusion versus tumor grade
A total of 7 low grade tumors and 24 high grade tumors
were analyzed. For both readers, the Kep values were higher
(33.6% to 40.1%) and the Ve values were lower (31.4% to
55.8%) in high grade tumors compared to low grade ones.
There was a significant difference in Ve values for reader
Perfusion MR imaging in musculoskeletal sarcomas 477

Table 1 Tumor histologic type, grade and necrosis ratio.

Patient number Histology FNCLCC grade Necrosis ratio
1 Leiomyosarcoma 2 1
2 Metastatic osteosarcoma 3 2
3 Liposarcoma 3 1
4 Leiomyosarcoma 3 2
5 Myxofibrosarcoma 3 1
6 Spindle cell sarcoma 3 2
7 Osteosarcoma 3 2
8 Osteosarcoma 3 2
9 Synovial sarcoma 2 2
10 Ewing’s sarcoma 3 1
11 Ewing’s sarcoma 3 0
12 Myxofibrosarcoma 1 0
13 Spindle cell sarcoma 2 0
14 Osteosarcoma 3 2
15 Ewing’s sarcoma 3 1
16 Dedifferentiated liposarcoma 3 2
17 Fibrosclerosing sarcoma 2 1
18 Liposarcoma 3 1
19 Osteosarcoma 3 2
20 Osteosarcoma 3 1
21 Osteosarcoma 3 2
22 Osteosarcoma 3 2
23 Osteosarcoma 3 2
24 Ewing’s sarcoma 3 2
25 Osteosarcoma 3 2
26 Ewing’s sarcoma 3 2
27 Synovial sarcoma 2 0
28 Myxofibrosarcoma 3 1
29 Pleomorphic sarcoma 3 1
30 Liposarcoma 2 2
31 Osteosarcoma 3 2
FNCLCC indicates Fédération nationale des centres de lutte contre le cancer (French Federation of Cancer Centers).

tumor grade. In high grade tumors, the Ktrans values were

higher for reader 1 (18.9% to 21%) and considerably lower
for reader 2 (37.3% to 39.1%) with no significant differences
(0.14 < P < 0.65).
For both readers, all semi-quantitative parameters were
3.1% to 49.4% lower in high grade tumors with respect to
low grade tumors. The highest variations were observed with
CER and AUC for which total tumor ROI demonstrated a 26.2
to 49.4% lower in high grade tumors but the differences did
not reach significance (0.1 < P < 0.74).

Perfusion versus histopathological necrosis

Figure 2. Box plot graph demonstrating the differences in distri-
bution of Ve ratios acquired by reader 2 between low grade and high
grade sarcomas (P = 0.02).
2 only (P = 0.06 and 0.02 for readers 1 and 2, respectively)
(Fig. 2). The Ktrans results showed no clear relationship with
ratio
There were 14 tumors with a low necrosis ratio and 17
tumors with a high necrosis ratio. The INI was significantly
different in these two groups for both readers (P < 0.005)
and the inter-reader reproducibility was considered to
be fair (ICC = 0.56). Mean INI ranged from 14.4% to 18.2%
in tumors with low necrosis ratios and 33.5% to 45.1% in
tumors with high necrosis ratios among the readers, which
represents a 56.9—59.8% increase (Fig. 3). When the INI
was categorized using FNCLCC criteria for tumor necrosis
478 P.A. Gondim Teixeira et al.

Table 2 Distribution of perfusion parameter values obtained with total tumor ROIs according to tumor grade and necrosis
rate.
Reader 1 CER AUC Max slope Ktrans Kep Ve
Grade Mean low grade 4.8 ± 2.8 6.5 ± 7.0 3.6 ± 2.7 4.7 ± 2.4 1.1 ± 0.4 4.5 ± 3.4
Mean high grade 3.4 ± 2.8 4.7 ± 7.8 3.1 ± 4.5 5.8 ± 6.3 1.8 ± 1.5 3.1 ± 1.2
Difference —28.3% —26.2% —15.8% 18.9% 36.1% —31.4%
P-value 0.27 0.61 0.74 0.65 0.3 0.06
Necrosis rate Mean low NR 5 ± 3.4 9 ± 10 5.1 ± 5.5 7.1 ± 6.5 2 ± 1.6 3.6 ± 2.1
Mean high NR 2.7 ± 1.7 1.8 ± 1.9 1.7 ± 1.3 4.3 ± 4.6 1.4 ± 1.1 3.3 ± 1.9
Difference —45.4% —79.8% —67.6% —39.8% —29.3% —6.4%
P-value 0.3 0.02* 0.03* 0.2 0.19 0.74

Reader 2 CER AUC Max slope Ktrans Kep Ve

Grade Mean low grade 4.2 ± 2.4 10.2 ± 13.4 4.1 ± 3.1 6.9 ± 4.4 1.2 ± 0.7 6.1 ± 3.6
Mean high grade 2.8 ± 1.9 5.2 ± 8.2 2.9 ± 3.4 4.3 ± 3.7 1.8 ± 2 2.8 ± 1.5
Difference —33.2% —49.4% —31.4% —37.3% 33.6% —54.8%
P-value 0.13 0.25 0.37 0.14 0.45 0.02*
Necrosis rate Mean low NR 4.3 ± 2.3 11.2 ± 12.7 5.2 ± 4.2 6.3 ± 4.1 2.2 ± 2.5 4.4 ± 3.2
Mean high NR 2.2 ± 1.2 2.2 ± 1.8 1.5 ± 0.9 3.7 ± 3.6 1.5 ± 0.9 2.8 ± 1.5
Difference —50.2% —80.0% —71.1% —41.1% —43.3% —36.4%
P-value 0.01* 0.03* 0.04* 0.08 0.2 0.1
CER indicates contrast enhancement ratio. AUC indicates area under the curve. Max slope indicates maximum slope of increase. Ktrans
indicates transfer constant from the plasma to the extravascular extracellular space. kep indicates backflux constant. Ve indicates
extravascular extracellular space volume.
* Indicates statistically significant P-value.

(0 — no necrosis; 1 — less than 50% necrosis; 2 — more than
50% necrosis), tumor necrosis was underestimated with
respect to histologic evaluation in 32.2% to 58.1% of tumors
for readers 1 and 2.
The MR perfusion parameters studied were well associ-
ated with histologic tumor necrosis. For both readers, AUC
and maximum slope of increase values were significantly
lower in tumors with high necrosis ratios for both read-
ers (0.01 < P < 0.046). CER values were only significant for
reader 1 (P = 0.30 and 0.01 for readers 1 and 2). For both
readers, perfusion parameters were 44.7—53.7% lower in
patients with high necrosis ratios compared to patients with
low necrosis ratios. The AUC yielded greater differences
between tumors with low and high necrosis ratios. The AUC
was 80.3% and 79.8% lower in tumors with high necrosis
ratios for readers 1 and 2 (Fig. 4).
The permeability parameters Ktrans and Kep were also
decreased in tumors with a high necrosis ratio for both read-
ers. Ve values also decreased for reader 2 but increased
for reader 1. The degree of reduction was lesser that what
was seen with semi-quantitative parameters (6.4 to 49.2%
for readers 1 and 2) and none of these differences were
statistically significant (0.1 < P < 0.99).
Discussion
We have found that semi-quantitative MR perfusion parame-
ters provide information with respect to the degree of tumor
necrosis. In addition, we found that MR perfusion parameters
are associated with an excellent interobserver reproducibil-
ity (ICC > 0.84). The AUC and the maximum slope values were
significantly lower in tumors with high necrosis ratios with
respect to tumors with low necrosis ratios. The AUC showed
the highest variation and is regarded as a robust, widely
available and reproducible perfusion parameter [21]. The
INI was significantly higher when tumors with high grades
of histologic necrosis were compared to tumors with low
grade necrosis. INI presented a fair ICC and tended to under-
estimate necrosis with respect to histology. This finding is
most likely related to the fact that tumor perfusion is an
indirect indicator of necrosis while, histologically, cellular
necrosis can be assessed directly. Non-invasive tumor necro-
sis with INI and AUC assessment could be easily integrated on
daily practice and could be useful to evaluate the treatment
response of patients undergoing adjuvant therapy [1,5].
Permeability parameters presented a week association
with tumor grade. Kep and Ve yielded greater differences
between tumors with low and high grade. This finding is
consistent with literature data and the same perfusion
parameters have been shown to correlate with survival rates
in patients with osteosarcoma by two different authors
[22,23]. Ve was 31% to 55% lower in tumors with high differ-
entiation/grade, and these differences were significant for
one of the readers. This can be at least partially explained
by the higher degree of cellularity of high grade tumors,
which tends to reduce the extravascular extracellular space
[24]. Although not statistically significant, Kep was 43—64%
higher in tumors with high grade, which could be related to
the higher capillary permeability in high grade tumors.
The lack of association between permeability parame-
ters and tumor grade could be, at least partially, related
to the higher technical variability of permeability param-
eters [25]. This variation is likely multifactorial, related
Perfusion MR imaging in musculoskeletal sarcomas 479

Figure 3. A 46-year-old woman with a fibromyxoid sarcoma of the left leg. A. Oblique coronal perfusion image in the arterial phase
demonstrating a heterogeneously enhancing mass (arrowheads) with central necrosis (star). The INI was estimated as 34—38.4%. B. Area
under the curve color map demonstrating a clear differentiation of perfusion in the viable (arrowheads) and necrotic tumor zones (star).
C. Macroscopic aspect of the tumor in a coronal section of the surgical specimen. A homogeneous necrotic area is seen at the upper aspect
of the tumor (star). D. Histological section demonstrating tumor necrosis (star) area, which represented less than 50% of the total tumor
volume (× 25).

to higher complexity of the calculations required for these
parameters (tissue gadolinium concentration estimation and
pharmacokinetic model fitting) [20]. AIF selection could
be an important source of variation [26]. Moreover, sig-
nal saturation phenomena can take place in larger vessels
leading to AIF underestimation with an impact on calcu-
lated parameters [27]. T1 variations in pathologic tissue and
poor pharmacokinetic model fitting are additional technical
sources of permeability parameter variation [25]. The dis-
cordant findings in Ktrans values between readers 1 and 2
when tumor grade was considered can be at least partially
explained by the previously mentioned technical variation
issues. Studies, performed with more robust MR perfusion
protocols (same coils, external reference for T1 value esti-
mation, better methods of AIF selection etc.) are needed
to further explore the relationship between permeability
parameters and tumor grading.
Our study has several limitations. The number of patients
included was small due to the low prevalence of MSK
sarcomas and the strict inclusion criteria, which limited
the number of statistically significant variations found. A
considerable number of patients were under adjuvant ther-
apy, which likely influenced the amount of observed tumor
necrosis. This fact probably explains why semi-quantitative
perfusion parameters were invariably lower in high grade
tumors a seemingly paradoxical finding. Because the objec-
tive of this work was to compare perfusion parameters
with histologic tumor features (as opposed to non-invasive
tumor aggressiveness assessment), the influence of adju-
vant therapy in the presented results is limited. Finally,
480
Figure 4. Box plot graph demonstrates the differences in distri-
bution of area under the curve (AUC) values in low and high necrosis
rate tumors.
there were variations in the injection rates used for perfu-
sion acquisition. In our institution, injection rate is adapted
to patient body habitus, age and history of capillary frailty
to avoid contrast injection-related complications. Because
only tumor/normal muscle ratios were evaluated, the influ-
ence of the injection rate variation was controlled.
In conclusion, semi-quantitative MR perfusion parame-
ters have an excellent reproducibility and are associated
with the degree of histologic tumor necrosis in muscu-
loskeletal sarcomas. Although further studies are needed,
our results suggest that INI calculation could represent a
non-invasive assessment method for determining the degree
of tumor necrosis and for further patient follow-up. The util-
ity of permeability parameters for determining tumor grade
needs further investigations.
Acknowledgements
This work was supported by the Societé française de radi-
ologie (SFR) and the Collège des enseignants de radiologie
de France (CERF) through a research grant.
Disclosure of interest
The authors declare that they have no competing interest.
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