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Magnetic resonance diffusion tensor imaging of the testis: Preliminary observations
European Journal of Radiology 95 (2017) 265–270
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European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Research article
Magnetic resonance diffusion tensor imaging of the testis: Preliminary observations
MARK
⁎
Athina C. Tsilia, , Alexandra Ntorkoua, Loukas Astrakasb, Ekaterini Boukalia, Dimitrios Giannakisc, Vasilios Maliakasa, Nikolaos Sofikitisc, Maria I. Argyropouloua a b c
Department of Clinical Radiology, Medical School, University of Ioannina, University Campus, 45110, Ioannina, Greece Department of Medical Physics, Medical School, University of Ioannina, University Campus, 45110, Ioannina, Greece Department of Urology, Medical School, University of Ioannina, University Campus, 45110, Ioannina, Greece
A R T I C L E I N F O
A B S T R A C T
Keywords: Diffusion Diffusion tensor imaging Magnetic resonance imaging Testes Testicular neoplasms
Introduction: To evaluate the feasibility of testis diffusion tensor imaging (DTI), to determine normative apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values and to assess the efficacy of DTI in characterizing testicular pathology. Materials and methods: Fifty-six men underwent MRI of the scrotum, including DTI. Parametric and non-parametric statistical tests were used to compare the ADC and FA between the cranial, middle and lower thirds of normal testis and between the bilateral testicular thirds. Comparison between the ADC and FA of normal testis, malignant and benign testicular lesions was performed. Results: No significant differences of the ADC and FA in normal testis between the cranial, middle and lower thirds and between the bilateral testicular thirds were found. ADC was significantly lower in malignancies compared to normal testis (P = 0.006) and benign testicular lesions (P = 0.006). FA was significantly higher both in malignancies (P = 0.001) and benign lesions (P < 0.001) compared to normal testis. FA in malignancies did not differ from FA in benign lesions (P = 0.221) Conclusions: This study shows the feasibility of testis DTI. Both ADC and FA significantly differ between testicular lesions and normal testis, although FA did not show an incremental diagnostic value compared to ADC in lesion differentiation.
1. Introduction Diffusion-weighted imaging (DWI) is a functional imaging technique used to assess the displacement distribution of the water molecules in living tissues, providing information for the structure and geometric organization [1,2]. Recent work addressing on the role of DWI in the interpretation of testicular pathology includes various applications, such as the detection and localization of impalpable testes, the early diagnosis of testicular torsion, the detection of testicular fibrosis in men with varicocele and the characterization of testicular mass lesions [3–10]. As diffusion is in fact a three-dimensional process, molecular mobility in tissues may occur with different probabilities in various directions that means in an anisotropic manner, especially in tissues with a specifically oriented organization. Diffusion tensor imaging (DTI) was developed on the basis of DWI to demonstrate the direction and speed of water molecule diffusion [11,12]. DTI can provide both apparent ⁎
diffusion coefficient (ADC) and fractional anisotropy (FA) values, which may reflect physiological characteristics and pathologic alterations at microscopic level [11,12]. Significant advances in the characterization of tissue microstructure and pathophysiology by means of DTI, originally in neuroimaging and musculoskeletal imaging have been reported [11–14]. DTI also has been applied in the evaluation of myocardium after infarction, in normal prostate and detection of prostatic carcinoma, in normal breast and differentiation of breast lesions, in normal and pathologic kidneys, in normal and pathologic liver, in normal pancreas and detection of pancreatic carcinoma, in anal canal, in normal uterus and in the evaluation of the female pelvic floor [11–23]. As to our knowledge, the anisotropy of the normal testis and the possible diagnostic value of DTI for differential diagnosis of testicular pathology have not been investigated. The purpose of this prospective study was to evaluate the feasibility of testis DTI, to determine normative ADC and FA values and to assess the efficacy of the technique in
Corresponding author. E-mail addresses: [email protected], [email protected] (A.C. Tsili), [email protected] (A. Ntorkou), [email protected] (L. Astrakas), [email protected] (E. Boukali), [email protected] (D. Giannakis), [email protected] (V. Maliakas), [email protected] (N. Sofikitis), [email protected] (M.I. Argyropoulou). http://dx.doi.org/10.1016/j.ejrad.2017.08.037 Received 25 June 2017; Accepted 28 August 2017 0720-048X/ © 2017 Elsevier B.V. All rights reserved.
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testis, with care not to overlap each other. The ROIs also were manually drawn to be as large as possible on areas of testicular lesions. Three different ROIs were placed on each testicular lesion and the measurements were averaged. Care was taken to exclude artifacts and areas of hemorrhage and/or necrosis, with the aid of the corresponding T1WI, T2WI and subtracted DCE T1WI.
the characterization of various testicular diseases. 2. Materials and methods 2.1. Patient population From June 2013 until January 2017, 56 men (age range, 17–76 years; mean age, 41 years) were referred for scrotal MRI with various clinical indications: vague scrotal pain and/or painless scrotal enlargement (n = 37); signs of acute epididymitis/epididymoorchitis (n = 10); painless, palpable mass (n = 7); recent penile trauma (n = 1), and recent penile enlargement (n = 1). The standard of reference included clinical and imaging follow-up, surgical and pathologic results. In cases of testicular malignancies, the time interval between MRI and radical orchiectomy was less than two weeks. The institution’s Review Board approved the study. All participants were informed about the study and written consent was obtained from all of them.
2.4. Statistical analyses Statistical analysis was performed using IBM SPSS version 20.0 (IBM, Inc., Armonk, NY, USA). The normality of distribution of parameters was assessed by a Kolmogorov-Smirnov test. The cranial, middle and caudal thirds of each testis were compared and analyzed by a oneway repeated-measures analysis of variance (ANOVA) test, when the data revealed a normal distribution. Comparisons between the bilateral testicular thirds were made using a paired samples t-test. Non-parametric tests, including the Kruskall-Wallis one-way analysis of variance and the Mann-Whitney U test were used to compare differences among measurements, if data did not assume a normal distribution. Two different control subgroups were selected in order to age-match the malignant and benign groups. Parametric and non-parametric statistical tests were used to compare the ADC and FA of normal testis to that of malignant and benign testicular lesions. Statistical significance was set at P-value’s of < 0.05.
2.2. MR protocol All MR examinations were performed on a 1.5-T scanner (Philips Medical Systems, Cleveland, OH, USA), with the use of a circular surface coil. Patients were examined in the supine position, with the testes placed at a similar distance from the coil, by placing a towel beneath them, and the penis draped on the lower anterior abdominal wall. Conventional sequences used for data analysis included transverse spinecho T1-weighted (T1WI) (TR/TE, 500–650/13–15 ms) and axial, sagittal and coronal fast spin-echo T2-weighted (T2WI) (TR/TE, 4000/ 100–120 ms). These images were of 3–4 mm section thickness, with a 0.5 mm intersection gap. The image matrix was 180 × 256 mm and the field of view (FOV) was 240 × 270 mm. DTI (TR/TE, 3756/131 ms) was performed along the coronal plane, during quiet breathing, using fat-saturated single-shot spin-echo planar imaging sequence and the following parameters: ACQ Matrix (M × P), 128 × 87; FOV, 250 × 227 mm2; slice thickness, 3,0 mm; intersection gap, 0 mm; number of signals averaged (NSA), 2; water excitation with b-values of 0 and 700 s/mm−2 and six diffusion directions. The total acquisition time was 2,07 min. Coronal subtracted dynamic contrast-enhanced (DCE) images, using a three-dimensional fast field-echo sequence (TR/TE, 9/4.1 ms) also were used for data interpretation (flip angle: 35°; section thickness, 4 mm; no intersection gap; matrix, 256 × 256 mm; FOV, 219 × 219 mm; and 60 s per sequence). Peripheral intravenous tubing with a 22-gauge catheter placed in a subcutaneous vein of the antecubital fossa was performed. Seven consecutive sets were acquired immediately after the rapid injection of 0.2 mmol of gadolinium chelate compounds per kilogram of bodyweight, performed manually and followed by a flush of 20 mL of physiologic saline solution, with no interval between them. Each of the seven data sets obtained after contrast medium administration was subtracted section by section, using the unenhanced data as a mask and commercially available software.
3. Results Τhirty eight out of one hundred and twelve testes were excluded from measurements due to the following: significant hydrocele (n = 4), testis malposition (n = 2), signal heterogeneity of the testis (n = 2), presence of very small, intratesticular tumor, difficult to measure, proved to correspond to benign Leydig cell tumor on pathology (n = 1), contralateral testes in men with testicular malignancies (n = 7), bilateral testes in men with varicocele (n = 20), contralateral testis in a patient with left varicocele and segmental testicular infarction (n = 1) and testicular implant (n = 1). Therefore, a total number of 74 testes were measured, including measurements in 56 normal testes and 18 testicular lesions, seven of which were malignant and 11 benign. Fifty six testes from 36 men (age range: 17–76 years; mean age: 44 years) were characterized as ‘normal’ based on the signal intensity on conventional sequences and/or the absence of abnormal testicular lesions found during subsequent clinical and/or sonographic follow-up studies. ADC followed a normal distribution as evaluated using the Kolmogorov-Smirnov test. The mean ADC ± std ( × 10−3 mm2/s) in the cranial, middle and lower testicular thirds was 1.14 ± 0.16, 1.16 ± 0.17, and 1.15 ± 0.16, respectively. ANOVA analysis showed no differences between the three groups (F = 0.183, degrees of freedom = 2, P = 0.833, Table 1). The ADC in the bilateral testicular thirds in 20 participants was included in the analysis. No significant differences were found (Table 2). Non-parametric tests were used for FA comparisons. The median FA in the cranial, middle and lower testicular thirds was 0.11, 0.11, and 0.11, respectively. Νo differences between the three groups were found (degrees of freedom = 2; P = 0.963, Table 3). FA was not different in the bilateral testicular thirds (Table 4). All tumors (n = 7) proved to represent testicular germ cell neoplasms (TGCNs) on pathology, four of which were seminomas and three nonseminomatous neoplasms (embryonal carcinoma, n = 1; embryonal carcinoma, teratoma, yolk sac tumor, n = 2). The age of patients with testicular malignancies ranged from 20 to 42 years, with a mean age of 32 years. The mean ± s.d. of ADC ( × 10−3 mm2/s) and the median of FA in TGCNs were 0.82 ± 0.31 and 0.26 (range: 0.18-0.42), respectively (Figs. 2 and 3). Benign testicular lesions included 10 cases of acute orchitis and one case of segmental testicular infarction. The age of patients with benign testicular pathologies ranged from 24 to 75 years,
2.3. Image analysis Two radiologists in consensus (ACT and AN, with 13 and four years of experience, each in scrotal MRI), blinded to the final diagnosis, analyzed the MRI data. The DW trace image, ADC map, and FA map were automatically generated using the DTI processing software on the Philips workstation and sent to the hospital picture archiving and communication system (PACS). Using coronal T2WI as guidance, coronal ADC and FA maps at the level of the mediastinum testis were selected for measurements. Three identical circular regions of interest (ROIs) were drawn in the cranial, middle and caudal thirds of the bilateral testes, to obtain the average ADC and FA values of normal testis (Fig. 1). ROIs were as large as possible to include the majority of normal 266
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Fig. 1. Normal MRI findings. (a) Coronal T2WI shows bilateral normal testes. A small amount of hydrocele is seen bilaterally (arrowheads, normal finding). Coronal (b) ADC and (c) colorcoded FA maps show ROIs selection in the right testis. The ADC (×10−3 mm2/ s) in the cranial, middle and lower thirds of the right and left testis is 1.13, 1.1, 1.07 and 1.05, 1.08, 1.02, respectively. The FA in the cranial, middle and lower thirds of the right and left testis is 0.06, 0.06, 0.05 and 0.09, 0.10, 0.08, respectively.
with a mean age of 50 years. The mean ± s.d. of ADC ( × 10−3 mm2/ s) and the median of FA in benign testicular lesions were 1.16 ± 0.15 and 0.20 (range: 0.16-0.36), respectively (Figs. 4 and 5). ADC in TGCNs was lower than that in normal testis, and that in benign testicular lesions. FA in TGCNs and benign testicular lesions was higher than that in normal testis. The independent-samples t-test showed a difference between the ADC in testicular carcinomas and normal testis of age-matched controls (n = 16, 1.14 ± 0.19 × 10−3 mm2/s, P = 0.006) and between the ADC in carcinomas and benign testicular lesions (P = 0.006). No differences between the ADC in benign testicular lesions and normal testis of age-matched controls (n = 22, 1.15 ± 0.15 × 10−3 mm2/s, P = 0.767) were observed (Table 5). The Mann Whitney U test showed a significant difference between the FA in testicular malignancies and normal testis of age-matched controls (n = 16, median: 0.11, range: 0.05–0.28, P = 0.001) and between the FA in benign testicular lesions and normal testis of age-matched controls (n = 22, median: 0.11, range: 0.05–0.18, P < 0.001), but not between the FA in malignancies and benign testicular lesions (P = 0.221) (Table 5).
Table 2 Number of bilateral testes, mean ADC ± std (×10−3 mm2/s) and paired samples t-test analysis results. Group
n
cranial middle lower
mean ADC ± std
20 20 20
P
RT testis
LT testis
1.13 ± 0.17 1.49 ± 0.17 1.11 ± 0.14
1.11 ± 0.17 1.11 ± 0.17 1.14 ± 0.17
0.474 0.064 0.141
Table 3 Comparison of FA between thirds of normal testis (P: Kruskal-Wallis test).
median maximum minimum
n
Cranial
Middle
Caudal
P
56 56 56
0.11 0.33 0.06
0.11 0.29 0.06
0.11 0.23 0.05
0.963
Table 4 Median, maximum and minimum of FA in bilateral testicular thirds and Mann- Whitney U test analysis results.
4. Discussion DWI is a functional imaging technique based on the measurement of increased or restricted microscopic diffusion movements of water molecules in tissues [1,2]. A few recent studies have reported the diagnostic performance of the technique in the characterization of testicular mass lesions [6,7]. In a previous retrospective study of 23 testicular lesions, an overall accuracy of 91%, 87% and 100%, respectively has been reported, when using conventional MRI data alone, DWI alone and DWI combined with conventional sequences in their characterization [7]. The ADC in TGCNs was lower than that in normal testis and various benign testicular lesions [7]. Algebally et al. reported a sensitivity of 93.3%, specificity of 90%, positive predictive value of 87.5%, and negative predictive value of 94.7% for a cut-off ADC of less than 0.99 in the characterization of testicular lesions [6]. However, diffusion is a three-dimensional process, and molecular mobility in organized tissues, such as brain white matter, muscle, kidney and breast is not necessarily the same in all directions [11,12]. DWI does not allow analysis of diffusion in multiple directions. DTI is a development from DWI, which provides additional information on
Group
Cranial Middle Lower
n
20 20 20
median of FA
maximum of FA
minimum of FA
RT
LT
RT
LT
RT
LT
0.11 0.11 0.11
0.10 0.11 0.12
0.33 0.29 0.23
0.27 0.24 0.20
0.06 0.06 0.05
0.06 0.08 0.08
P
0.063 0.659 0.369
diffusion direction and degree of directed diffusion, by analyzing water diffusion in different directions. Structural integrity and microstructural changes can be indirectly assessed by DTI [11–23]. By using DTI, we are able to obtain both ADC and FA values [11–23]. DTI has been extensively used to evaluate brain disorders, for example demyelinating diseases, cerebral ischemia, brain maturation, and brain tumors [11–13]. More recently, normal breast presenting with fibroglandular tissue orientated along tubular ducts and Cooper ligaments demonstrated obvious anisotropy and DTI proved an adjunct tool in the characterization of breast lesions [17]. Kidney is another well-
Table 1 ANOVA analysis between the ADC (×10−3 mm2/s) in cranial, middle and caudal thirds of normal testis.
mean ADC ± std maximum minimum
n
Cranial
Middle
Caudal
P
F
56 56 56
1.14 ± 0.16 1.53 0.86
1.16 ± 0.17 1.66 0.81
1.15 ± 0.16 1.56 0.83
0.183
0.833
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Fig. 2. Right testicular seminoma. (a) Coronal T2WI demonstrates upper pole right intratesticular mass, mainly hypointense (arrowhead). Small, bilateral hydrocele (normal finding). Coronal corresponding (b) ADC and (c) color-coded FA maps. The ADC (×10−3 mm2/s) and FA values of testicular seminoma (arrowhead) are 0.70 and 0.20, respectively.
[25]. Although, it is generally accepted that the human scrotum is asymmetrical, with the left testis occupying a lower level than the right and the right testis larger than the left, no relationship of ADC with normal testes asymmetry has been confirmed [25]. To our knowledge, the results of the present study are the first to demonstrate that the testis, like the liver has an isotropic diffusion pattern. The median FA in normal testicular parenchyma was 0.11. No significant differences of the FA between the cranial, middle and lower thirds of normal testis and between bilateral testicular thirds were found. Although the testis is a structured organ, presenting with seminiferous tubules, septa and vessels radiating towards the mediastinum, no obvious anisotropy was detected on the present study. Our results are difficult to explain. In water, at room temperature, water molecules move over distances around 100 μm at one second. During typical diffusion times of about 50 ms, water molecules move on average around 25 μm, which is much smaller than the 150–300 μm diameters of the normal seminiferous tubules (and larger than the few μm diameters of the white matter fibers, a classical example of an anisotropic tissue) [11,12]. Therefore, low values of FA in normal testis may be related to the large size of the seminiferous tubules and their irregular, highly convolved shape. The present study demonstrated that ADC in testicular carcinomas, and specifically TGCNs was significantly lower compared to ADC in normal testis and benign testicular lesions, consistent with the findings of previous studies [6–10]. ADC in benign testicular lesions, and specifically acute orchitis and segmental testicular infarction did not differ significantly from ADC in normal testis in the current report. Other studies reported higher ADC in benign testicular lesions, when compared to that in normal testicular parenchyma [6,7]. Histopathologic features in cases of orchitis, such as the presence of interstitial hemorrhage in the acute phase and the presence of fibrosis and adhesions in the healing phase may explain the lower ADCs, measured in this study cohort [26]. The conflicting results in the case of segmental testicular infarction may be related to marked thickening of seminiferous
structured organ, with radial orientation of tubules, collecting ducts and blood vessels, where DTI is feasible. The technique has been proved useful in the evaluation of a variety of kidney pathologies, including chronic kidney diseases, diabetic nephropathy, glomerulonephritis, renal masses and assessment of renal allograft function [18–20]. There are currently no published reports on the use of DTI for testis imaging. The present study shows the feasibility of testis DTI on a 1.5 T system, with b values of 0 and 700 s/mm−2 and the potential role of the technique in the characterization of various testicular diseases. This study also establishes the normative FA values of testicular parenchyma. The mean ± s.d. of ADC (×10−3 mm/s) in normal testis was 1.15 ± 0.16, which is in accordance with previous studies [6,7]. Testis is an example of normal organ causing restricted diffusion due to its structural complexity [24]. A capsule of dense connective tissue, the tunica albuginea, surrounds each testis. The tunica albuginea is thickened on the posterior surface of the testis to form a conical mass of connective tissue, the mediastinum testis. From the mediastinum, delicate, incomplete fibrous septa radiate towards the tunica albuginea and divide the testicular parenchyma into about 300 lobuli testes. Each lobule is occupied by one to four convoluted seminiferous tubules. The testis has about 250–1000 seminiferous tubules in its lobules, with each tubule measuring about 150–300 μm in diameter and 30–80 cm long in length. The combined length of the tubules of one testis is about 250 m. The spaces between the seminiferous tubules are filled with interstitial loose connective tissue, rich in blood and lymphatic vessels, nerves, and endocrine interstitial cells (Leydig cells). Toward the apices of the lobules, the seminiferous tubules become straight (tubuli recti) and enter the mediastinum to form a labyrinthine system of cavities, the rete testis. Ten to 20 efferent ductules connect the rete testis to the head of the epididymis. The described complexity of normal anatomy of the testis explains the restriction of water molecules diffusion [24]. The ADC in the cranial, middle and caudal thirds of normal testis showed no differences. Similar to a previous report, we found no significant differences in the ADC between the bilateral testicular thirds
Fig. 3. Embryonal carcinoma. (a) Coronal T2WI depicts small, heterogeneous, sharply-delineated right intratesticular mass (arrow). Coronal corresponding (b) ADC and (c) color-coded FA maps. The ADC (×10−3 mm2/s) and FA values of testicular carcinoma (arrow) are 0.98 and 0.29, respectively.
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Fig. 4. Left acute epididymoorchitis. (a) Coronal T2WI demonstrates hypointensity of the left testis and the ipsilateral epididymis (arrowhead), due to inflammation. Normal right testis. Coronal corresponding (b) ADC and (c) color-coded FA maps. The ADC (×10−3 mm2/s) and FA values of acute orchitis are 1.14 and 0.19, respectively. The ADC (×10−3 mm2/s) and FA values of contralateral normal testis are 1.17 and 0.09, respectively. Fig. 5. Left segmental testicular infarction. The patient was referred with vague scrotal pain. He reported a history of left testicular trauma, seven years ago and recently treated acute epididymoorchitis ipsilaterally. Coronal (a) T2WI and (b) subtracted DCE images show a heterogeneous left intratesticular mass lesion (arrowhead), mainly of low T2 signal. The lesion is avascular with marked rim enhancement. Coronal corresponding (c) ADC and (d) colorcoded FA maps. The ADC (×10−3 mm2/ s) and FA values of left testicular lesion (arrowhead) are 1.14 and 0.32, respectively.
Table 5 Independent-samples t-test and Mann-Whitney U test showing the difference of mean ± s.d. of ADC (×10−3 mm2/s) and of median of FA, respectively, between testicular carcinomas, benign testicular lesions and normal testes of age-matched controls.
mean ± s.d. of ADC median of FA
Malignant (n = 7)
Normal testes (n = 16)
P
Malignant (n = 7)
Benign (n = 11)
P
Benign (n = 11)
Malignant (n = 7)
P
0.82 ± 0.31 0.26
1.14 ± 0.19 0.11
0.006 0.001
0.82 ± 0.31 0.26
1.16 ± 0.15 0.20
0.006 0.221
1.16 ± 0.15 0.20
0.82 ± 0.31 0.26
0.767 < 0.001
It is the P values, showing the statistical significance.
compared to FA in normal testis. Diffusion in malignancies is more restricted and more anisotropic when compared to normal tissues, resulting in low ADC and high FA, and this was proved in the present study [15,21,28]. Erturk et al. in a retrospective study of 77 focal liver lesions, including metastases, hemangiomas and simple cysts assessed the potential role of ADC and FA in their discrimination [21]. The
tubules basement membrane in the subacute phase and presence of sclerosed seminiferous tubules with hyalinized interstitial fibrosis in the chronic phase [27]. Besides ADC, FA also was measured in various testicular lesions. The median of FA in TGCNs and benign testicular lesions was 0.26 and 0.20, respectively. FA was significantly higher in testicular malignancies, 269
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authors found significant differences between malignant and benign liver lesions, with lower ADC and higher FA in liver metastases, reflecting their higher cell density and malignant behavior [21]. Kinoshita et al. in their study of malignant brain tumors with DTI suggested a positive correlation between FA and tumor cell density [28]. A relationship between FA and tumor grade also has been documented, with high-grade tumors presenting with increased FA and decreased ADC, while low-grade tumors having low cellularity and randomly arranged cells presenting with low FA and high ADC [15,29]. While anisotropy values in the present study had the potential to provide help in the characterization of various testicular lesions, ADC exhibited the highest differential diagnostic power. Benign testicular lesions had ADC lower than expected and higher FA, reducing the differences between malignant and benign lesions and therefore the diagnostic value of FA in lesion characterization. Studies using DTI in the characterization of breast lesions also reported that FA was not a significant discriminator [17,30]. Partridge et al. although found lower diffusion anisotropy in malignancies compared to normal breast, they could not differentiate between malignant and benign lesions by FA measurements [30]. Baltzer et al. in a study of DTI at 1.5 T with the b values of 0 and 1000 s/mm−2, found a lower ADC and FA in malignant breast tumors, with ADC being more discriminative [17]. The small sample and the small number of testicular diseases limit this study. A small number of testicular malignancies were included, histologically proved to represent TGCNs. Larger number of TGCNs, including both seminomas and nonseminomatous tumors and other histologic types of testicular carcinomas, including non-germ cell tumors and secondary malignancies, should be assessed to evaluate the potential role of DTI in their characterization. In addition, benign testicular lesions were primarily cases of acute orchitis and one case of segmental testicular infarction. A wide range of benign testicular entities should be assessed to investigate if additional information from DTI could help in the characterization of the benign nature of these lesions. Another potential criticism is that only a consensus reading of the MRI data by two radiologists was performed and therefore, no interobserver variability was assessed. 5. Conclusions We have demonstrated the feasibility of testis DTI on a 1.5 T system with b values of 0 and 700 s/mm−2 and the efficacy of the technique in the characterization of various testicular diseases. Both ADC and FA significantly differ between testicular lesions and normal testis, although FA did not show an incremental diagnostic value compared to ADC in differentiating malignant from benign testicular lesions. Further investigation, including a wide range of testicular lesions, in highstrength systems together with advanced diffusion sequences may validate the role of DTI in the evaluation of testicular pathology. References [1] R. Bammer, Basic principles of diffusion-weighted imaging, Eur. J. Radiol. 45 (2003) 169–184. [2] O. Dietrich, A. Biffar, A. Baur-Melnyk, M.F. Reiser, Technical aspects of MR diffusion imaging of the body, Eur. J. Radiol. 76 (2010) 314–322. [3] M. Kantarci, S. Doganay, A. Yalcin, Y. Aksoy, B. Yilmaz-Cankaya, B. Salman, Diagnostic performance of diffusion-weighted MRI in the detection of nonpalpable undescended testes: comparison with conventional MRI and surgical findings, AJR Am. J. Roentgenol. 195 (2010) W268–273.
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Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Research article
Magnetic resonance diffusion tensor imaging of the testis: Preliminary observations
MARK
⁎
Athina C. Tsilia, , Alexandra Ntorkoua, Loukas Astrakasb, Ekaterini Boukalia, Dimitrios Giannakisc, Vasilios Maliakasa, Nikolaos Sofikitisc, Maria I. Argyropouloua a b c
Department of Clinical Radiology, Medical School, University of Ioannina, University Campus, 45110, Ioannina, Greece Department of Medical Physics, Medical School, University of Ioannina, University Campus, 45110, Ioannina, Greece Department of Urology, Medical School, University of Ioannina, University Campus, 45110, Ioannina, Greece
A R T I C L E I N F O
A B S T R A C T
Keywords: Diffusion Diffusion tensor imaging Magnetic resonance imaging Testes Testicular neoplasms
Introduction: To evaluate the feasibility of testis diffusion tensor imaging (DTI), to determine normative apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values and to assess the efficacy of DTI in characterizing testicular pathology. Materials and methods: Fifty-six men underwent MRI of the scrotum, including DTI. Parametric and non-parametric statistical tests were used to compare the ADC and FA between the cranial, middle and lower thirds of normal testis and between the bilateral testicular thirds. Comparison between the ADC and FA of normal testis, malignant and benign testicular lesions was performed. Results: No significant differences of the ADC and FA in normal testis between the cranial, middle and lower thirds and between the bilateral testicular thirds were found. ADC was significantly lower in malignancies compared to normal testis (P = 0.006) and benign testicular lesions (P = 0.006). FA was significantly higher both in malignancies (P = 0.001) and benign lesions (P < 0.001) compared to normal testis. FA in malignancies did not differ from FA in benign lesions (P = 0.221) Conclusions: This study shows the feasibility of testis DTI. Both ADC and FA significantly differ between testicular lesions and normal testis, although FA did not show an incremental diagnostic value compared to ADC in lesion differentiation.
1. Introduction Diffusion-weighted imaging (DWI) is a functional imaging technique used to assess the displacement distribution of the water molecules in living tissues, providing information for the structure and geometric organization [1,2]. Recent work addressing on the role of DWI in the interpretation of testicular pathology includes various applications, such as the detection and localization of impalpable testes, the early diagnosis of testicular torsion, the detection of testicular fibrosis in men with varicocele and the characterization of testicular mass lesions [3–10]. As diffusion is in fact a three-dimensional process, molecular mobility in tissues may occur with different probabilities in various directions that means in an anisotropic manner, especially in tissues with a specifically oriented organization. Diffusion tensor imaging (DTI) was developed on the basis of DWI to demonstrate the direction and speed of water molecule diffusion [11,12]. DTI can provide both apparent ⁎
diffusion coefficient (ADC) and fractional anisotropy (FA) values, which may reflect physiological characteristics and pathologic alterations at microscopic level [11,12]. Significant advances in the characterization of tissue microstructure and pathophysiology by means of DTI, originally in neuroimaging and musculoskeletal imaging have been reported [11–14]. DTI also has been applied in the evaluation of myocardium after infarction, in normal prostate and detection of prostatic carcinoma, in normal breast and differentiation of breast lesions, in normal and pathologic kidneys, in normal and pathologic liver, in normal pancreas and detection of pancreatic carcinoma, in anal canal, in normal uterus and in the evaluation of the female pelvic floor [11–23]. As to our knowledge, the anisotropy of the normal testis and the possible diagnostic value of DTI for differential diagnosis of testicular pathology have not been investigated. The purpose of this prospective study was to evaluate the feasibility of testis DTI, to determine normative ADC and FA values and to assess the efficacy of the technique in
Corresponding author. E-mail addresses: [email protected], [email protected] (A.C. Tsili), [email protected] (A. Ntorkou), [email protected] (L. Astrakas), [email protected] (E. Boukali), [email protected] (D. Giannakis), [email protected] (V. Maliakas), [email protected] (N. Sofikitis), [email protected] (M.I. Argyropoulou). http://dx.doi.org/10.1016/j.ejrad.2017.08.037 Received 25 June 2017; Accepted 28 August 2017 0720-048X/ © 2017 Elsevier B.V. All rights reserved.
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testis, with care not to overlap each other. The ROIs also were manually drawn to be as large as possible on areas of testicular lesions. Three different ROIs were placed on each testicular lesion and the measurements were averaged. Care was taken to exclude artifacts and areas of hemorrhage and/or necrosis, with the aid of the corresponding T1WI, T2WI and subtracted DCE T1WI.
the characterization of various testicular diseases. 2. Materials and methods 2.1. Patient population From June 2013 until January 2017, 56 men (age range, 17–76 years; mean age, 41 years) were referred for scrotal MRI with various clinical indications: vague scrotal pain and/or painless scrotal enlargement (n = 37); signs of acute epididymitis/epididymoorchitis (n = 10); painless, palpable mass (n = 7); recent penile trauma (n = 1), and recent penile enlargement (n = 1). The standard of reference included clinical and imaging follow-up, surgical and pathologic results. In cases of testicular malignancies, the time interval between MRI and radical orchiectomy was less than two weeks. The institution’s Review Board approved the study. All participants were informed about the study and written consent was obtained from all of them.
2.4. Statistical analyses Statistical analysis was performed using IBM SPSS version 20.0 (IBM, Inc., Armonk, NY, USA). The normality of distribution of parameters was assessed by a Kolmogorov-Smirnov test. The cranial, middle and caudal thirds of each testis were compared and analyzed by a oneway repeated-measures analysis of variance (ANOVA) test, when the data revealed a normal distribution. Comparisons between the bilateral testicular thirds were made using a paired samples t-test. Non-parametric tests, including the Kruskall-Wallis one-way analysis of variance and the Mann-Whitney U test were used to compare differences among measurements, if data did not assume a normal distribution. Two different control subgroups were selected in order to age-match the malignant and benign groups. Parametric and non-parametric statistical tests were used to compare the ADC and FA of normal testis to that of malignant and benign testicular lesions. Statistical significance was set at P-value’s of < 0.05.
2.2. MR protocol All MR examinations were performed on a 1.5-T scanner (Philips Medical Systems, Cleveland, OH, USA), with the use of a circular surface coil. Patients were examined in the supine position, with the testes placed at a similar distance from the coil, by placing a towel beneath them, and the penis draped on the lower anterior abdominal wall. Conventional sequences used for data analysis included transverse spinecho T1-weighted (T1WI) (TR/TE, 500–650/13–15 ms) and axial, sagittal and coronal fast spin-echo T2-weighted (T2WI) (TR/TE, 4000/ 100–120 ms). These images were of 3–4 mm section thickness, with a 0.5 mm intersection gap. The image matrix was 180 × 256 mm and the field of view (FOV) was 240 × 270 mm. DTI (TR/TE, 3756/131 ms) was performed along the coronal plane, during quiet breathing, using fat-saturated single-shot spin-echo planar imaging sequence and the following parameters: ACQ Matrix (M × P), 128 × 87; FOV, 250 × 227 mm2; slice thickness, 3,0 mm; intersection gap, 0 mm; number of signals averaged (NSA), 2; water excitation with b-values of 0 and 700 s/mm−2 and six diffusion directions. The total acquisition time was 2,07 min. Coronal subtracted dynamic contrast-enhanced (DCE) images, using a three-dimensional fast field-echo sequence (TR/TE, 9/4.1 ms) also were used for data interpretation (flip angle: 35°; section thickness, 4 mm; no intersection gap; matrix, 256 × 256 mm; FOV, 219 × 219 mm; and 60 s per sequence). Peripheral intravenous tubing with a 22-gauge catheter placed in a subcutaneous vein of the antecubital fossa was performed. Seven consecutive sets were acquired immediately after the rapid injection of 0.2 mmol of gadolinium chelate compounds per kilogram of bodyweight, performed manually and followed by a flush of 20 mL of physiologic saline solution, with no interval between them. Each of the seven data sets obtained after contrast medium administration was subtracted section by section, using the unenhanced data as a mask and commercially available software.
3. Results Τhirty eight out of one hundred and twelve testes were excluded from measurements due to the following: significant hydrocele (n = 4), testis malposition (n = 2), signal heterogeneity of the testis (n = 2), presence of very small, intratesticular tumor, difficult to measure, proved to correspond to benign Leydig cell tumor on pathology (n = 1), contralateral testes in men with testicular malignancies (n = 7), bilateral testes in men with varicocele (n = 20), contralateral testis in a patient with left varicocele and segmental testicular infarction (n = 1) and testicular implant (n = 1). Therefore, a total number of 74 testes were measured, including measurements in 56 normal testes and 18 testicular lesions, seven of which were malignant and 11 benign. Fifty six testes from 36 men (age range: 17–76 years; mean age: 44 years) were characterized as ‘normal’ based on the signal intensity on conventional sequences and/or the absence of abnormal testicular lesions found during subsequent clinical and/or sonographic follow-up studies. ADC followed a normal distribution as evaluated using the Kolmogorov-Smirnov test. The mean ADC ± std ( × 10−3 mm2/s) in the cranial, middle and lower testicular thirds was 1.14 ± 0.16, 1.16 ± 0.17, and 1.15 ± 0.16, respectively. ANOVA analysis showed no differences between the three groups (F = 0.183, degrees of freedom = 2, P = 0.833, Table 1). The ADC in the bilateral testicular thirds in 20 participants was included in the analysis. No significant differences were found (Table 2). Non-parametric tests were used for FA comparisons. The median FA in the cranial, middle and lower testicular thirds was 0.11, 0.11, and 0.11, respectively. Νo differences between the three groups were found (degrees of freedom = 2; P = 0.963, Table 3). FA was not different in the bilateral testicular thirds (Table 4). All tumors (n = 7) proved to represent testicular germ cell neoplasms (TGCNs) on pathology, four of which were seminomas and three nonseminomatous neoplasms (embryonal carcinoma, n = 1; embryonal carcinoma, teratoma, yolk sac tumor, n = 2). The age of patients with testicular malignancies ranged from 20 to 42 years, with a mean age of 32 years. The mean ± s.d. of ADC ( × 10−3 mm2/s) and the median of FA in TGCNs were 0.82 ± 0.31 and 0.26 (range: 0.18-0.42), respectively (Figs. 2 and 3). Benign testicular lesions included 10 cases of acute orchitis and one case of segmental testicular infarction. The age of patients with benign testicular pathologies ranged from 24 to 75 years,
2.3. Image analysis Two radiologists in consensus (ACT and AN, with 13 and four years of experience, each in scrotal MRI), blinded to the final diagnosis, analyzed the MRI data. The DW trace image, ADC map, and FA map were automatically generated using the DTI processing software on the Philips workstation and sent to the hospital picture archiving and communication system (PACS). Using coronal T2WI as guidance, coronal ADC and FA maps at the level of the mediastinum testis were selected for measurements. Three identical circular regions of interest (ROIs) were drawn in the cranial, middle and caudal thirds of the bilateral testes, to obtain the average ADC and FA values of normal testis (Fig. 1). ROIs were as large as possible to include the majority of normal 266
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Fig. 1. Normal MRI findings. (a) Coronal T2WI shows bilateral normal testes. A small amount of hydrocele is seen bilaterally (arrowheads, normal finding). Coronal (b) ADC and (c) colorcoded FA maps show ROIs selection in the right testis. The ADC (×10−3 mm2/ s) in the cranial, middle and lower thirds of the right and left testis is 1.13, 1.1, 1.07 and 1.05, 1.08, 1.02, respectively. The FA in the cranial, middle and lower thirds of the right and left testis is 0.06, 0.06, 0.05 and 0.09, 0.10, 0.08, respectively.
with a mean age of 50 years. The mean ± s.d. of ADC ( × 10−3 mm2/ s) and the median of FA in benign testicular lesions were 1.16 ± 0.15 and 0.20 (range: 0.16-0.36), respectively (Figs. 4 and 5). ADC in TGCNs was lower than that in normal testis, and that in benign testicular lesions. FA in TGCNs and benign testicular lesions was higher than that in normal testis. The independent-samples t-test showed a difference between the ADC in testicular carcinomas and normal testis of age-matched controls (n = 16, 1.14 ± 0.19 × 10−3 mm2/s, P = 0.006) and between the ADC in carcinomas and benign testicular lesions (P = 0.006). No differences between the ADC in benign testicular lesions and normal testis of age-matched controls (n = 22, 1.15 ± 0.15 × 10−3 mm2/s, P = 0.767) were observed (Table 5). The Mann Whitney U test showed a significant difference between the FA in testicular malignancies and normal testis of age-matched controls (n = 16, median: 0.11, range: 0.05–0.28, P = 0.001) and between the FA in benign testicular lesions and normal testis of age-matched controls (n = 22, median: 0.11, range: 0.05–0.18, P < 0.001), but not between the FA in malignancies and benign testicular lesions (P = 0.221) (Table 5).
Table 2 Number of bilateral testes, mean ADC ± std (×10−3 mm2/s) and paired samples t-test analysis results. Group
n
cranial middle lower
mean ADC ± std
20 20 20
P
RT testis
LT testis
1.13 ± 0.17 1.49 ± 0.17 1.11 ± 0.14
1.11 ± 0.17 1.11 ± 0.17 1.14 ± 0.17
0.474 0.064 0.141
Table 3 Comparison of FA between thirds of normal testis (P: Kruskal-Wallis test).
median maximum minimum
n
Cranial
Middle
Caudal
P
56 56 56
0.11 0.33 0.06
0.11 0.29 0.06
0.11 0.23 0.05
0.963
Table 4 Median, maximum and minimum of FA in bilateral testicular thirds and Mann- Whitney U test analysis results.
4. Discussion DWI is a functional imaging technique based on the measurement of increased or restricted microscopic diffusion movements of water molecules in tissues [1,2]. A few recent studies have reported the diagnostic performance of the technique in the characterization of testicular mass lesions [6,7]. In a previous retrospective study of 23 testicular lesions, an overall accuracy of 91%, 87% and 100%, respectively has been reported, when using conventional MRI data alone, DWI alone and DWI combined with conventional sequences in their characterization [7]. The ADC in TGCNs was lower than that in normal testis and various benign testicular lesions [7]. Algebally et al. reported a sensitivity of 93.3%, specificity of 90%, positive predictive value of 87.5%, and negative predictive value of 94.7% for a cut-off ADC of less than 0.99 in the characterization of testicular lesions [6]. However, diffusion is a three-dimensional process, and molecular mobility in organized tissues, such as brain white matter, muscle, kidney and breast is not necessarily the same in all directions [11,12]. DWI does not allow analysis of diffusion in multiple directions. DTI is a development from DWI, which provides additional information on
Group
Cranial Middle Lower
n
20 20 20
median of FA
maximum of FA
minimum of FA
RT
LT
RT
LT
RT
LT
0.11 0.11 0.11
0.10 0.11 0.12
0.33 0.29 0.23
0.27 0.24 0.20
0.06 0.06 0.05
0.06 0.08 0.08
P
0.063 0.659 0.369
diffusion direction and degree of directed diffusion, by analyzing water diffusion in different directions. Structural integrity and microstructural changes can be indirectly assessed by DTI [11–23]. By using DTI, we are able to obtain both ADC and FA values [11–23]. DTI has been extensively used to evaluate brain disorders, for example demyelinating diseases, cerebral ischemia, brain maturation, and brain tumors [11–13]. More recently, normal breast presenting with fibroglandular tissue orientated along tubular ducts and Cooper ligaments demonstrated obvious anisotropy and DTI proved an adjunct tool in the characterization of breast lesions [17]. Kidney is another well-
Table 1 ANOVA analysis between the ADC (×10−3 mm2/s) in cranial, middle and caudal thirds of normal testis.
mean ADC ± std maximum minimum
n
Cranial
Middle
Caudal
P
F
56 56 56
1.14 ± 0.16 1.53 0.86
1.16 ± 0.17 1.66 0.81
1.15 ± 0.16 1.56 0.83
0.183
0.833
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Fig. 2. Right testicular seminoma. (a) Coronal T2WI demonstrates upper pole right intratesticular mass, mainly hypointense (arrowhead). Small, bilateral hydrocele (normal finding). Coronal corresponding (b) ADC and (c) color-coded FA maps. The ADC (×10−3 mm2/s) and FA values of testicular seminoma (arrowhead) are 0.70 and 0.20, respectively.
[25]. Although, it is generally accepted that the human scrotum is asymmetrical, with the left testis occupying a lower level than the right and the right testis larger than the left, no relationship of ADC with normal testes asymmetry has been confirmed [25]. To our knowledge, the results of the present study are the first to demonstrate that the testis, like the liver has an isotropic diffusion pattern. The median FA in normal testicular parenchyma was 0.11. No significant differences of the FA between the cranial, middle and lower thirds of normal testis and between bilateral testicular thirds were found. Although the testis is a structured organ, presenting with seminiferous tubules, septa and vessels radiating towards the mediastinum, no obvious anisotropy was detected on the present study. Our results are difficult to explain. In water, at room temperature, water molecules move over distances around 100 μm at one second. During typical diffusion times of about 50 ms, water molecules move on average around 25 μm, which is much smaller than the 150–300 μm diameters of the normal seminiferous tubules (and larger than the few μm diameters of the white matter fibers, a classical example of an anisotropic tissue) [11,12]. Therefore, low values of FA in normal testis may be related to the large size of the seminiferous tubules and their irregular, highly convolved shape. The present study demonstrated that ADC in testicular carcinomas, and specifically TGCNs was significantly lower compared to ADC in normal testis and benign testicular lesions, consistent with the findings of previous studies [6–10]. ADC in benign testicular lesions, and specifically acute orchitis and segmental testicular infarction did not differ significantly from ADC in normal testis in the current report. Other studies reported higher ADC in benign testicular lesions, when compared to that in normal testicular parenchyma [6,7]. Histopathologic features in cases of orchitis, such as the presence of interstitial hemorrhage in the acute phase and the presence of fibrosis and adhesions in the healing phase may explain the lower ADCs, measured in this study cohort [26]. The conflicting results in the case of segmental testicular infarction may be related to marked thickening of seminiferous
structured organ, with radial orientation of tubules, collecting ducts and blood vessels, where DTI is feasible. The technique has been proved useful in the evaluation of a variety of kidney pathologies, including chronic kidney diseases, diabetic nephropathy, glomerulonephritis, renal masses and assessment of renal allograft function [18–20]. There are currently no published reports on the use of DTI for testis imaging. The present study shows the feasibility of testis DTI on a 1.5 T system, with b values of 0 and 700 s/mm−2 and the potential role of the technique in the characterization of various testicular diseases. This study also establishes the normative FA values of testicular parenchyma. The mean ± s.d. of ADC (×10−3 mm/s) in normal testis was 1.15 ± 0.16, which is in accordance with previous studies [6,7]. Testis is an example of normal organ causing restricted diffusion due to its structural complexity [24]. A capsule of dense connective tissue, the tunica albuginea, surrounds each testis. The tunica albuginea is thickened on the posterior surface of the testis to form a conical mass of connective tissue, the mediastinum testis. From the mediastinum, delicate, incomplete fibrous septa radiate towards the tunica albuginea and divide the testicular parenchyma into about 300 lobuli testes. Each lobule is occupied by one to four convoluted seminiferous tubules. The testis has about 250–1000 seminiferous tubules in its lobules, with each tubule measuring about 150–300 μm in diameter and 30–80 cm long in length. The combined length of the tubules of one testis is about 250 m. The spaces between the seminiferous tubules are filled with interstitial loose connective tissue, rich in blood and lymphatic vessels, nerves, and endocrine interstitial cells (Leydig cells). Toward the apices of the lobules, the seminiferous tubules become straight (tubuli recti) and enter the mediastinum to form a labyrinthine system of cavities, the rete testis. Ten to 20 efferent ductules connect the rete testis to the head of the epididymis. The described complexity of normal anatomy of the testis explains the restriction of water molecules diffusion [24]. The ADC in the cranial, middle and caudal thirds of normal testis showed no differences. Similar to a previous report, we found no significant differences in the ADC between the bilateral testicular thirds
Fig. 3. Embryonal carcinoma. (a) Coronal T2WI depicts small, heterogeneous, sharply-delineated right intratesticular mass (arrow). Coronal corresponding (b) ADC and (c) color-coded FA maps. The ADC (×10−3 mm2/s) and FA values of testicular carcinoma (arrow) are 0.98 and 0.29, respectively.
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Fig. 4. Left acute epididymoorchitis. (a) Coronal T2WI demonstrates hypointensity of the left testis and the ipsilateral epididymis (arrowhead), due to inflammation. Normal right testis. Coronal corresponding (b) ADC and (c) color-coded FA maps. The ADC (×10−3 mm2/s) and FA values of acute orchitis are 1.14 and 0.19, respectively. The ADC (×10−3 mm2/s) and FA values of contralateral normal testis are 1.17 and 0.09, respectively. Fig. 5. Left segmental testicular infarction. The patient was referred with vague scrotal pain. He reported a history of left testicular trauma, seven years ago and recently treated acute epididymoorchitis ipsilaterally. Coronal (a) T2WI and (b) subtracted DCE images show a heterogeneous left intratesticular mass lesion (arrowhead), mainly of low T2 signal. The lesion is avascular with marked rim enhancement. Coronal corresponding (c) ADC and (d) colorcoded FA maps. The ADC (×10−3 mm2/ s) and FA values of left testicular lesion (arrowhead) are 1.14 and 0.32, respectively.
Table 5 Independent-samples t-test and Mann-Whitney U test showing the difference of mean ± s.d. of ADC (×10−3 mm2/s) and of median of FA, respectively, between testicular carcinomas, benign testicular lesions and normal testes of age-matched controls.
mean ± s.d. of ADC median of FA
Malignant (n = 7)
Normal testes (n = 16)
P
Malignant (n = 7)
Benign (n = 11)
P
Benign (n = 11)
Malignant (n = 7)
P
0.82 ± 0.31 0.26
1.14 ± 0.19 0.11
0.006 0.001
0.82 ± 0.31 0.26
1.16 ± 0.15 0.20
0.006 0.221
1.16 ± 0.15 0.20
0.82 ± 0.31 0.26
0.767 < 0.001
It is the P values, showing the statistical significance.
compared to FA in normal testis. Diffusion in malignancies is more restricted and more anisotropic when compared to normal tissues, resulting in low ADC and high FA, and this was proved in the present study [15,21,28]. Erturk et al. in a retrospective study of 77 focal liver lesions, including metastases, hemangiomas and simple cysts assessed the potential role of ADC and FA in their discrimination [21]. The
tubules basement membrane in the subacute phase and presence of sclerosed seminiferous tubules with hyalinized interstitial fibrosis in the chronic phase [27]. Besides ADC, FA also was measured in various testicular lesions. The median of FA in TGCNs and benign testicular lesions was 0.26 and 0.20, respectively. FA was significantly higher in testicular malignancies, 269
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authors found significant differences between malignant and benign liver lesions, with lower ADC and higher FA in liver metastases, reflecting their higher cell density and malignant behavior [21]. Kinoshita et al. in their study of malignant brain tumors with DTI suggested a positive correlation between FA and tumor cell density [28]. A relationship between FA and tumor grade also has been documented, with high-grade tumors presenting with increased FA and decreased ADC, while low-grade tumors having low cellularity and randomly arranged cells presenting with low FA and high ADC [15,29]. While anisotropy values in the present study had the potential to provide help in the characterization of various testicular lesions, ADC exhibited the highest differential diagnostic power. Benign testicular lesions had ADC lower than expected and higher FA, reducing the differences between malignant and benign lesions and therefore the diagnostic value of FA in lesion characterization. Studies using DTI in the characterization of breast lesions also reported that FA was not a significant discriminator [17,30]. Partridge et al. although found lower diffusion anisotropy in malignancies compared to normal breast, they could not differentiate between malignant and benign lesions by FA measurements [30]. Baltzer et al. in a study of DTI at 1.5 T with the b values of 0 and 1000 s/mm−2, found a lower ADC and FA in malignant breast tumors, with ADC being more discriminative [17]. The small sample and the small number of testicular diseases limit this study. A small number of testicular malignancies were included, histologically proved to represent TGCNs. Larger number of TGCNs, including both seminomas and nonseminomatous tumors and other histologic types of testicular carcinomas, including non-germ cell tumors and secondary malignancies, should be assessed to evaluate the potential role of DTI in their characterization. In addition, benign testicular lesions were primarily cases of acute orchitis and one case of segmental testicular infarction. A wide range of benign testicular entities should be assessed to investigate if additional information from DTI could help in the characterization of the benign nature of these lesions. Another potential criticism is that only a consensus reading of the MRI data by two radiologists was performed and therefore, no interobserver variability was assessed. 5. Conclusions We have demonstrated the feasibility of testis DTI on a 1.5 T system with b values of 0 and 700 s/mm−2 and the efficacy of the technique in the characterization of various testicular diseases. Both ADC and FA significantly differ between testicular lesions and normal testis, although FA did not show an incremental diagnostic value compared to ADC in differentiating malignant from benign testicular lesions. Further investigation, including a wide range of testicular lesions, in highstrength systems together with advanced diffusion sequences may validate the role of DTI in the evaluation of testicular pathology. References [1] R. Bammer, Basic principles of diffusion-weighted imaging, Eur. J. Radiol. 45 (2003) 169–184. [2] O. Dietrich, A. Biffar, A. Baur-Melnyk, M.F. Reiser, Technical aspects of MR diffusion imaging of the body, Eur. J. Radiol. 76 (2010) 314–322. [3] M. Kantarci, S. Doganay, A. Yalcin, Y. Aksoy, B. Yilmaz-Cankaya, B. Salman, Diagnostic performance of diffusion-weighted MRI in the detection of nonpalpable undescended testes: comparison with conventional MRI and surgical findings, AJR Am. J. Roentgenol. 195 (2010) W268–273.
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