The Egyptian Journal of Radiology and Nuclear Medicine (2015) 46, 715–726

Egyptian Society of Radiology and Nuclear Medicine

The Egyptian Journal of Radiology andNuclearMedicine

www.elsevier.com/locate/ejrnmwww.sciencedirect.com

ORIGINAL ARTICLE

Role of dynamic contrast enhanced MR perfusion

in differentiation between benign and malignant

tumors

* Corresponding author. Mobile: +01001567500.

E-mail addresses: Drmagdaa@hotmail.com (M. El Backry),

Magdashady@gmail.com (M. Shady), eamany2@yahoo.com

(A.E. Mousa), Mona_Zaky1982@hotmail.com (M.M. Zaky).1 Mobile: +201222449377.2 Mobile: +01000858400.3 Mobile: +20122709804.

Peer review under responsibility of Egyptian Society of Radiology and

Nuclear Medicine.

http://dx.doi.org/10.1016/j.ejrnm.2015.01.0010378-603X � 2015 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier B.V. All rights reserv

Magda El Backry1, Magda Shady

2, Amani Ezzat Mousa

3,

Mona Mahmoud Zaky *

Diagnostic Radiology Department, Faculty of medicine, Mansoura university, Egypt

Received 13 October 2014; accepted 6 January 2015Available online 23 April 2015

KEYWORDS

Dynamic MRI;

Head and neck tumors;

Wash in rate

Abstract Aim: Evaluation of diagnostic accuracy of dynamic contrast enhanced (DCE) MRI in

differentiating benign from malignant head and neck tumors using both Quantitative and semi

quantitative analysis.

Patients and methods: 55 patients with head and neck masses underwent DCEMRI at 1.5 T Philips

Ingenia MR scanner. Their enhancement curve patterns, Time to peak, wash in and washout rates

were analyzed and compared in benign and malignant tumors.

Results: 81.8% of benign tumors had gradual progressing and plateau curves, while 93.3% of

malignant tumors had plateau and fast curves. TTP, wash in and wash out rates were significantly

different between benign and malignant tumors. Using TTP cut off value of 83.3 s differentiated

benign from malignant tumors with a sensitivity of 84.8% and specificity of 77.3%, while wash

in rate at cut off value of 15.4 1/s provided a sensitivity of 87.9% and specificity of 90.9%, wash

out rates provided at cut off value of 5.75 1/s, a sensitivity of 81.8% and specificity of 90.9%.

Conclusion: Dynamic contrast enhanced MRI is a promising method for differentiation between

benign and malignant head and neck tumors, wash in rate is the most specific parameter used.� 2015 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier

B.V. All rights reserved.

1. Introduction

Head and neck cancer is common in several regions of theworld. Overall, head and neck cancer accounts for more than550,000 cases annually worldwide (1).

Imaging has an important role in staging, planning treat-

ment and post-treatment follow up of patients with head andneck cancer (2).

ed.

Table 1 Shows histopathological entities of patients.

Histopathology No %

Benign Abscess 1 1.8

Inverted papilloma 3 5.5

Lymphoid hyperplasia 1 1.8

Neurofibroma 1 1.8

Polyp 1 1.8

Angiofibroma 3 5.5

Dermoid cyst 1 1.8

Chondroma 2 3.6

Epidermoid 1 1.8

Vocal cord papilloma 1 1.8

Glomus vagale 1 1.8

Pleomorphic adenoma 4 7.2

Warthin tumor 2 3.6

Malignant Adenocarcinoma 3 5.5

Adenoid cystic carcinoma 4 7.3

Malignant fibrous histiocytoma 1 1.8

Melanoma 1 1.8

Mucoepidermoid carcinoma 1 1.8

Ameloblastic fibrosarcoma 1 1.8

Non hodgkin lymphoma 1 1.8

Olfactory neuroblastoma 1 1.8

Osteosarcoma 1 1.8

Papillary carcinoma 3 5.5

Anaplastic carcinoma 1 1.8

Chondrosarcoma 2 3.6

Squamous cell carcinoma 12 21.8

Fibrosarcoma 1 1.8

716 M. El Backry et al.

Magnetic resonance imaging (MRI) is effective for diagnos-ing tumors and has some advantages over other techniques,especially in detecting soft tissue lesions. However, conven-

tional MRI is not able to differentiate normal highly vascularstructures, e.g. intrinsic tongue muscles and pharyngealmucosa from neoplasm, also not capable of determining

whether a tumor is benign or malignant. It has been reportedthat dynamic contrast-enhanced MRI (DCE-MRI) is usefulfor differentiating normal highly vascular structures from

neoplasm, allowing the investigator to determine the trueextent of a lesion, also it is helpful in differentiating tumors,and many investigators have attempted to use it to identify dif-ferences between benign and malignant tumors, as well as to

assess the malignancy of tumors (3).So, head and neck imaging is shifting from the morpholog-

ical to the functional techniques as these techniques are used to

assess the complex interrelated processes in the cancermicroenvironment, such as hypoxia and angiogenesis (4).

Dynamic contrast enhanced magnetic resonance imaging

(DCE-MRI) is an important imaging technique used inoncology assessment as it is able to identify changes in tissuephysiology.

A common approach in the analysis of DCE-MRI isdrawing (ROI) in region of interest and observes how theaverage signal intensity of the ROI varies with time. It hasbeen reported that the time versus signal intensity curve, is

useful for differentiating head and neck tumors (5).Although the semi quantitative evaluations have been

widely applied, they do not provide information on the under-

lying pharmacokinetic nature in the tissue. Moreover, an anal-ysis based on the signal intensity (SI) is predominantly affectedby the scan parameters, and it is operator dependant (6).

So, there was also a need for a noninvasive quantitativemethod which enables the quantification of contrast agentexchange between the intravascular and the interstitial space (7).

Few researches studied the role of either quantitative orsemi quantitative analysis in specific region in head and neck,e.g. sinonasal (6), palate (8).

The aim of our study was to present an overview of diag-

nostic accuracy of DCE-MRI in differentiation betweenbenign and malignant head and neck tumors as a whole, andto compare specificity and sensitivity of both quantitative

and semi quantitative analytical methods.

2. Patients and methods

2.1. Patients

This prospective study included Fifty seven patients (with amean age of 44.84 ± 16.64 years); 38 males and 19 femaleswho underwent DCE-MRI, these patients came to our hospital

with head and neck masses between June 2012 and September2014. They were referred from ENT, oncology center andradiotherapy departments of Mansoura University Hospitals.

All patients underwent DCE-MRI as a part of routine post

contrast MRI study using Philips Ingenia 1.5 T. Two patientswere excluded from this study whose lesions were too small toallow its signal intensity to be calculated. The final diagnosis of

the masses was confirmed by histopathological examination asshown in Table 1. Thus, we finally evaluated 55 patients withhead and neck tumors.

2.2. MRI protocol

Our study was performed on Philips Ingenia 1.5 T MRI scan-ner in all of 55 cases, with the same scanning parameters. A

precontrast reference scan was first performed through theregion of interest (ROI), and this was followed by routine headand neck MR imaging protocol (axial 5 mm T2WI with fat

suppression and axial T1WI parallel to hard palate from skullbase to thoracic inlet, coronal and axial T1WI fat suppressedimage), then intravenous administration of gadolinium

(GD-DTPA).T1-weighted image (600/20/2 [TR/TE/number of excita-

tions]; field of view, 18 cm; matrix, 256 · 192; section thick-

ness, 2 mm; section gap, 1 mm) and fast spin-echo (fatsuppressed) T2-weighted image (4000/90/4; field of view,18 cm; matrix, 256 · 256; section thickness, 2 mm; sectiongap, 1 mm) were obtained before the administration of con-

trast agent. A dynamic2D (axial T1WI fat suppressed) fastspoiled gradient recalled sequence (10.4/2.3/1; flip angle, 30�;field of view, 18 cm; matrix, 256 · 128; section thickness,

4 mm; section gap, 1 mm) with total acquisition time of 240 sduring bolus injection (0.3 mmol/kg) of single dose contrastagent gadopentetate dimeglumine (Magnevist) with a maxi-

mum dose of 30 ml at a rate of 2.5 ml/S given intravenouslyvia an automatic injector.

2.3. Image postprocessing

Multiphase dynamic images were analyzed using Philipsextended work space (EWS) release 2.6 workstation. Weplaced a region of interest within an area of 10 mm2 (the area

Role of DCE MR perfusion in differentiation 717

in which the diameter of the tumor was greatest, cystic parts ofthe tumors were avoided and this area showed the greatestdegree of early enhancement on the dynamic images). Time

signal intensity curve (TIC) after an injection of Gd-DTPAin the ROI of each examination was plotted. The obtainedTICs were classified into four types on the basis of TTP peak

(the time to peak enhancement) into four types: type A(gradual enhancement), type B (rapid enhancement and lowwashout), type C (rapid enhancement and high washout),

and type D (flat) (9).Wash-in rate (K trans) is defined as the rate of enhancement

between 10% and 90% of the signal intensity differencebetween maximum signal intensity post-enhancement

(SImax) and signal intensity prior to enhancement (SIbase).It was derived from the first-pass phase of signal intensityenhancement according to the following equation (10):

Wash in rate ¼ SImax � SIbaseð Þ � 0:8½ �SIbase � ðt90%� t10%Þ½ �

� �� 100

Wash-out rate (K ep) is the rate of monoexponential decay

of the enhancement signal in the tissue (i.e. vertebral body). Itwas derived from the enhancement signal decay phase accord-ing to the following equation:

y ¼ Span� expðktÞ þ Plateau

where y refers to the MR signal (Y-axis values) and t refersto time (X-axis values), Plateau refers to the MR signal valuewhen the contrast-enhancement decays to a plateau (10).

1-Time to peak

3-

AUC=0.84

1.0

0.8

0.6

0.4

0.2

0.0

Sens

itivi

ty

1.0

0.8

0.6

0.4

0.2

0.0

Sens

itivi

ty

0.0 0.2 0.4 0.6 0.8 1.0

1 - Specificity

0.0 0.2 0

1

Fig. 1 ROC curves for TTP, was

2.4. Image interpretation

Based on the findings on T1-weighted, T2-weighted, and postcontrast T1 fat suppressed images, dynamic contrast enhancedMRI images were evaluated by two experienced head and neck

radiologists in consensus with 18 and 7 years of experience.The region-of-interest (ROI) was placed in the solid part of

the lesion to avoid bias of low perfusion of the necrotic part.The ROI was inserted using oval shaped function.

From this ROI, the time intensity curve and time to peakvalue were automatically generated.

Quantitative analysis of the DCE-MRI data was automat-

ically performed using Philips extended work space (EWS)release 2.6 workstation giving color maps and values of washin and wash out rates.

Semi quantitative and quantitative interpretations of theDCE-MRI were done. Semi quantitative interpretation wasdone using TIC and TTP.

Quantitative interpretation was done by measuring wash inand wash out rate values.

2.5. Statistical analysis

Data are expressed as mean value ± SD for quantitative dataand as frequency (number-%) for qualitative data. Comparisonswere carried out by unpaired t test for parametric data. Inter-

group comparison of categorical data was performed by usingchi square test (X2-value). The sensitivity, specificity, positive

2 - Wash in

Wash out

AUC=0.94

AUC=0.91

1.0

0.8

0.6

0.4

0.2

0.0

Sens

itivi

ty

0.0 0.2 0.4 0.6 0.8 1.0

1 - Specificity

.4 0.6 0.8 1.0

- Specificity

h in and wash out parameters.

Fig. 2 Left maxillary squamous cell carcinoma in 44 years old male. (A) Axial T1 fat suppressed post contrast spin echo weighted image

shows intense enhancement. (B) TIC shows type C curve (gradual wash out). (C) TTP, wash in and wash out rates measures. (D) Wash in

rate. (E) Wash out rate.

718 M. El Backry et al.

Fig. 3 Left sided sphenopalatine nasopharyngeal angiofibroma in a male patient aged 16 years. (A) Axial T1 fat suppressed post

contrast spin echo weighted image shows intensely enhancing mass. (B) TIC shows type A curve. (C) TTP, wash in and wash out rates

measures. (D) Wash in rate. (E) Wash out rate.

Role of DCE MR perfusion in differentiation 719

Fig. 4 Warthin tumor of the left parotid gland of male patient aged 45 years. (A) Axial T1 spin echo fat suppressed post contrast

weighted image shows homogenous enhancement. (B) TIC shows type C curve (rapid wash out). (C) TTP, wash in and wash out rates

measures. (D) Wash in rate. (E) Wash out rate.

720 M. El Backry et al.

Fig. 5 Melanoma of the right side of the nasal cavity of female patient aged 58 years. (A) Axial T1 spin echo fat suppressed post contrast

weighted image shows intense homogenous enhancement. (B) TIC shows type C curve (rapid wash out). (C) TTP, wash in and wash out

rates measures. (D) Wash in rate. (E) Wash out rate.

Role of DCE MR perfusion in differentiation 721

Fig. 6 Malignant fibrous histiocytoma in a male patient aged 12 years. (A) Axial T1 spin echo fat suppressed post contrast weighted

image shows small intramuscular lesion of intense homogenous enhancement. (B) TIC shows type C curve (rapid wash out). (C) TTP,

wash in and wash out rates measures. (D) Wash in rate. (E) Wash out rate.

722 M. El Backry et al.

Fig. 7 Right vocal cord papilloma in a female patient aged 32 years. (A) Axial T1 fat suppressed post contrast spin echo weighted image

shows faintly enhancing mass. (B) TIC shows type A curve (gradual progressing curve). (C) TTP, wash in and wash out rates measures.

(D) Wash in rate. (E) Wash out rate.

Role of DCE MR perfusion in differentiation 723

Table 2 Results of TICs analysis. p value > 0.05 is considered

significant.

Groups p

Benign Malignant

No % No %

Type of curve A 7 31.8 1 3.0 0.01

B 11 50.0 8 24.2 0.2

C 2 9.1 23 69.7 0.004

D 2 9.1 1 3.0 0.6

Table 3 Results of mean value of TTP, wash in and wash out

rates. p value >0.05 is considered significant.

Groups p

Benign Malignant

Mean ± SD Mean ± SD

Time to peak 101.19 ± 25.03 74.83 ± 16.83 <0.001

Wash in rate (1/s) 9.98 ± 4.78 18.95 ± 4.36 <0.001

Wash out rate (1/S) 2.11 ± 3.24 9.47 ± 4.08 <0.001

724 M. El Backry et al.

predictive value, negative predictive value and accuracy of time topeak, wash in and wash out to differentiate between benign and

malignant tumors were determined at different cutoff points usingROC curve analysis to determine the best cutoff point as well asthe diagnostic power of each test. Differences were considered

statistically significant when p< 0.05. Analysis was done usingSPSS for Windows (17.0 version) (see Fig. 1).

3. Results

Twenty-two patients had benign tumors, while remaining 33had malignant tumors.

Of benign tumors 81.8% had types A (Figs. 3 and 7) and Bcurves (31.8% and 50%) respectively, while 93.9% of malig-nant tumors had types B and C (Figs. 2 and 4–6) curves(24.2% and 69.7%) with significant difference for curves A

and C for differentiation of benign and malignant tumors(p = 0.01 and p= 0.004), no significant difference for curvesB and D between benign and malignant tumors (p= 0.2 and

p= 0.6) (Table 2).There was significant difference in TTP between benign and

malignant tumors (Table 3). The results of ROC analysis of

TTP provided at cut off value of 83.3 s a sensitivity of84.8% and specificity of 77.3% with an area under curve(AUC) of 0.84 (Table 4).

Table 4 Positive predictive values (PPV), negative predictive value

diagnosis of malignant tumors in the head and neck.

Area under the curve (95% CI) Cutoff valu

Time to peak (s) 0.84(0.71–0.96) 83.3>

Wash in rate (1/s) 0.94(0.87–1.00) 15.4<

Wash out rate (1/s) 0.91(0.82–1.00) 5.75<

There was significant difference in wash in and wash outrates between benign and malignant tumors (p< 0.001)(Table 3). The results of ROC analysis of wash in rate at cut

off value of 15.4 1/s provided a sensitivity of 87.9% andspecificity of 90.9% with (AUC) of 0.94, those for wash outrates provided at cut off value of 5.75 with (AUC) of 0.91, a

sensitivity of 81.8% and specificity of 90.9% for differentiationof benign and malignant tumors (Table 4).

Warthin tumor shows type C curve and rapid wash out

rates than malignant tumors (Fig. 4).

4. Discussion

Conventional MRI helps in diagnosing head and neck tumors,but differentiating benign from malignant moreover is still dif-ficult in many situations; hence, the physiologic properties of

lesions can be estimated by kinetic studies after contrast-med-ium injection, we report in this study the utility of DCE-MRIby two different analytical methods (semiquantitative andquantitative) in differentiating benign and malignant tumors.

We firstly applied semi quantitative analysis by plotting SIagainst time. The use of the TIC is the most conventionalmethod of assessing a DCE-MR study.

Sasaki et al. (11) used visual analysis and classification ofTIC to differentiate between benign and malignant tumors asin our study. While Ziech et al. (12) used it to investigate the

activity of inflammatory processes, while Lavini et al. (13)usedit to assess the effect of drugs.

The majority of the studies were done in the musculoskele-tal system investigating bone, soft tissue tumors and inflamma-

tory processes (4,14,15).Takashima et al. (16)classified the TIC of 79 head and neck

lesions into five groups according to the time at which they dis-

played peak enhancement: type A, the curve peaked at 0–30 safter the administration of contrast medium; type B, the curvepeaked at 30–60 s after the administration of contrast medium;

type C, the curve peaked at 60–210 s after the administrationof contrast medium; type D, the curve displayed a gradualupward slope; and type E, the curve was flat.

Eida et al. (9) in agreement with us classified TIC into fourtypes: type A (gradual enhancement), type B (rapid enhance-ment and low washout), type C (rapid enhancement and highwashout), and type D (flat). In our study 81.8% of benign

tumors had types A and B curves (31.8% and 50% respec-tively), while 93.9% of malignant tumors had types B and Ccurves (24.2% and 69.7% respectively).

Study made by Sasaki et al. (17) on 44 patients with headand neck tumors revealed that benign lesions present flat,gradual progressing and fast curves types (D, A and C) in

disagreement with our study, while malignant tumors containfast and plateau curves types (C and B) in agreement with thepresent study.

s (PPV), sensitivity and specificity of DCE-MRI features in the

e Sensitivity Specificity PPV NPV Accuracy

84.8 77.3 84.8 77.3 81.8

87.9 90.9 93.5 83.3 89.1

81.8 90.9 93.1 76.9 85.5

Role of DCE MR perfusion in differentiation 725

The differences in types of curves happened between ourstudy and Sasaki et al. study could be explained by large num-ber of warthin tumors contained in their study which gave type

C curve.TTP in our study showed significant difference between

benign and malignant tumors, giving mean value of 101.19 s

for benign tumors and 74.83 s for malignant tumors with cutoff value of 83.3 s at (AUC of 0.84) giving specificity of 77.3%and sensitivity of 84.8%. These results were consistent with

Yabuuchi et al. (18) who studied TTP in 29 patients with salivarygland tumors and concluded that TTP of 120 s enabled the dif-ferentiation of pleomorphic adenomas from malignant tumors.

However the TIC shape analysis does not provide absolute

measures. It is dependent, affected by the length of the scan,and the scan parameters (TR/flip angle), all these factors caninfluence the final shape, resulting in the same tissue possibly

being classified differently when using different parameters (19).In contrast to semi-quantitative techniques, intrinsic physio-

logic information of tissue microcirculation can be provided by

quantitative techniques which depend on contrast concentrationcurves over time to observe the extravasation of contrastagent from the vascular space to the interstitial space (20).

Pharmacokinetic modeling of the DCE-MRI signal is used tocalculate the kinetic parameters such as wash in and wash outrates describing tumor and tissue permeability that are hallmarksof the angiogenic phenotype associated with most cancers (21).

In the current study, we found significant difference(p< 0.001) as regards wash in and wash out rates betweenbenign and malignant tumors in agreement with Junfang

et al. (6), and the present study demonstrated mean value ofwash in rate was 9.98 1/s for benign tumors and 18.95 1/s formalignant tumors, while mean value of wash out rate was

2.11 1/s for benign tumors and 9.47 1/s for malignant tumors.Different studies on malignant tumors of the breast, pros-

tate, cervix, liver, lung, rectum, brain, and head and neck

reported that malignant tumors had higher wash in rate(Ktrans) and washout rates (Kep) (20,22,23).

Although DCE-MRI is safe, non invasive, can be repeatedand performed on conventional MRI examination (19); how-

ever, there is some limitations to the routine clinical use ofDCE-MRI which is lack of standardized and optimized perfu-sion MRI protocols, lacking of simple and standardized perfu-

sion postprocessing software and apparent complexity ofperfusion MRI for nonexpert radiologists (24).

5. Conclusion

We concluded that DCE-MRI plays a superior role to the con-ventional MRI in differentiating benign from malignant head

and neck tumors.Quantitative parameters improve the accuracy of DCE-

MRI by studying the tissue pharmacokinetics and tissue prop-erties, and wash in rate was the best parameter used for differ-

entiation between benign and malignant tumors with cut offvalue 15.4 1/s giving a sensitivity of 87.9% and specificity of90.9% with (AUC) of 0.94.

6. Conflict of Interest

There is no conflict of interest to declare.

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