Diffusion tensor imaging parameters in testes with varicocele: a pilot study

Athina C. Tsili1, Olga N. Xiropotamou1, Alexandra Ntorkou1, Loukas G. Astrakas1, Vasilios Maliakas1, Nikolaos Sofikitis3, Maria I. Argyropoulou1

1Department of Clinical Radiology, 2Department of Medical Physics, 3Department of Urology, Medical School, University of Ioannina, University Campus, 45110, Ioannina, Greece

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European Society of Urogenital Radiology

2nd ESUR Teaching Course Multimodality Imaging Approach to Scrotal and Penile Pathologies

Introduction

Varicocele is one of the main causes of male infertility

Many controversies exist regarding the effect of varicocele on male infertility and whether repair leads to improvement of the fertility status

a non-invasive imaging technique providing answers to questions regarding which patients with varicocele are at risk for infertility and which will benefit after varicocele repair would be extremely useful

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Introduction

Diffusion tensor imaging (DTI) is an extension of diffusion MRI

DTI may assess diffusion anisotropy effects and directionality of water molecules in biological tissues, providing information on tissue microstructure and pathophysiology

many applications, including brain or spine white matter, muscles, myocardium, kidneys, prostate, breast…….

both apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values are measured

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Purpose

To measure the ADC and FA in testes of infertile men with varicocele and to assess interobserver agreement

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Subjects and Methods

23 consecutive infertile men, July 2016-January 2017

referred from the Urology department with the diagnosis of varicocele

clinical indications: infertility, testicular pain and/or scrotal swelling

excluded 7 participants: age less than 20 years (n=2), age more than 50 years (n=2), prior embolization (n=1), testicular germ cell neoplasm (n=1) and testicular microlithiasis (n=1)

Study cohort: 16 infertile men with varicocele (age range: 23-48 years;

mean age: 30 years; median age: 28 years)

Left varicocele (n=5), bilateral varicocele (n=11)

CDUS: to confirm diagnosis

maximal spermatic venous diameter (mSVD) measured at the upper pole of the testis, at the level of inguinal canal during resting condition and the Valsalva maneuver

Diagnosis of varicocele: presence retrograde flow (reflux) during normal respiration or during the Valsalva maneuver and a maximal vein diameter of 2 mm or more

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Subjects and Methods

14 age-matched controls (age range, 22-50 years, mean age: 36 years; median age: 34 years)

clinical indications: vague scrotal pain and/or painless scrotal enlargement (n= 13) and signs of acute epididymoorchitis (n = 1)

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MRI protocol

1.5T, circular surface coil, supine position, feet first

axial T1WI, axial and coronal T2WI

DTI protocol coronal fat-saturated single-shot spin-echo planar imaging sequence b-value: 0,700 s/mm2 TR/TE: 3756/131 ms ACQ Matrix (M×P): 128×87 FOV: 250×227 mm2

slice thickness: 3 mm no intersection gap NSA: 2

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MR data interpretation

testicular ADC and FA: measured by two radiologists independently, blinded to clinical and US data

three similar ROIs drawn in the cranial, middle and caudal thirds of each testis

three measurements were averaged

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Statistical analysis

Kolmogorov Smirnov test: assess normality of data distribution

Pearson correlation coefficient: interobserver agreement between ADC measured by two observers (observer 1, 2)

p < 0.01: statistically significant

very weak: 0.00-0.19, weak: 0.20-0.39, moderate: 0.40-0.59, strong: 0.60-0.79, very strong: 0.80-1.0

Independent Samples t test: compare ADC between testes in infertile men with varicocele and normal testes

Spearman’s Rho correlation coefficient: interobserver variability between FA measured by two observers

Man-Whitney U test: compare testicular FA between two groups

p < 0.05: statistically significant

ROC curve analysis, AUC: efficacy of DTI parameters in the diagnosis of varicocele

cutoff values to predict the diagnosis of varicocele

SPSS v.23.0

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Results

• 25 testes in infertile men with varicocele

excluded 6 testes in men with varicocele (testes contralateral to varicocele with normal sonographic findings, n=5; presence of artifacts onADC and FA maps, n=1)

• 26 normal testes

excluded 2 testes in controls (acute orchitis, n=1; presence of large spermatocele with pressure effects on the ipsilateral testis, n=1)

• mSVD at rest: 2.37 mm (range: 1.40-4.50 mm)

• mSVD during Valsalva: 3.04 mm (range: 2.10-6.50 mm)

Results: ADC very strong interobserver agreement (0.911, p < 0.01)

no statistically significant difference (p = 0.294)

mean±s.d. ADC (× 10-3 mm2/s) (observer 1)

infertile testes with varicocele: 1.10 ± 0.08

normal testes: 1.16 ± 0.17

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group ADC minimum maximum P

varicocele 1.10±0.08 0.98 1.28

0.294 controls 1.16±0.17 0.85 1.48

Results: FA very good interobserver variability (0.944, p < 0.01)

statistically significant difference (p < 0.001)

median of FA (observer 1)

infertile testes with varicocele: 0.07

normal testes: 0.11

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group median of FA minimum maximum P

varicocele 0.07 0.04 0.11

< 0.01 controls 0.11 0.05 0.28

Results AUC: 0.923

optimal cutoff of FA: 0.08

sensitivity: 88%

specificity: 93.5%

PPV: 91.6%

NPV: 90.6%

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Results • Histopathology in testes with varicocele: hypospermatogenesis, increase of Leydig cells,

thickening of the tubular basement membrane and of the tunica adventitia and tunica media of the spermatic veins with luminal narrowing, and increase of the interstitial fibrous tissue

• Hypospermatogenesis: quantitative decrease of spermatogenesis, thinning of the germinal epithelium, paucity of germinal cells causing the central lumen of the spermatic tubules to appears enlarged and sloughed immature spermatogenic cells within tubules

• decrease of germ cells and luminal enlargement possibly predominate

decrease of FA in testes with varicocele

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Conclusion To the best of our knowledge, this preliminary study represents the first report to

measure DTI parameters in infertile testes with varicocele

high reproducibility for measurements of testicular DTI parameters, with very good interobserver agreement

FA reflected the pathologic changes in infertile testes with varicocele with greater sensitivity than ADC

employment of DTI in a population of infertile men can serve as an adjunct tool for the diagnosis of varicocele

the ability to identify early signs of deranged spermatogenesis in testes of infertile men with varicocele based on imaging findings may have implications in determining cases that may benefit from varicocele repair

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Varicocele… -In De Medicina, written during the first century AD, Celsus credits the Greeks with the first description of a varicocele, and he recorded his own acute observation:

‘The veins are swollen and twisted over the testicle, which becomes smaller than its fellow, in as much as its nutrition has become defective’

Celsus himself is credited with the distinction between varicocele (dilation of surface veins) and “cirsocele” (dilation of deep veins)

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