**1. Introduction**

458 Endometriosis - Basic Concepts and Current Research Trends

[12] Nishimura K, Togashi K, Itoh K, Fujisawa I, Noma S, Kawamura Y, Nakano Y, Itoh H,

[13] Siegelman ES, Outwater E, Wang T, Mitchell DG. Solid pelvic masses caused by

[14] Bazot M, Darai E, Hourani R, Thomassin I, Cortez A, Uzan S, Buy JN. Deep pelvic

[15] Onbas O, Kantarci M, Alper F, Kumtepe Y, Durur I, Ingec M, Gursan N, Okur A.

[16] Togashi K, Nishimura K, Kimura I et al . Endometrial cysts: diagnosis with MR

[17] Fedele L, Piazzola E, Raffaelli R, Bianchi S. Bladder endometriosis: deep infiltrating

[18] Halleguier C, Chapron C, Dubuisson J B, Kinkel K, Fauconnier A, Vieira M et al..

[19] Umek W H, Morgan D M, Ashton-Miller J A, DeLancey J O L. Quantitative analysis of

[20] Ohba T, Mizutani H, Maeda T, Matsuura K, Okamura H. Evaluation of endometriosis in

[21] Zawin M, McCarthy S, Scoutt L, Comite F. Endometriosis: appearance and detection at

[22] Kinkel K, Chapron C, Balleyguier C, Fritel X, Dubuisson JB, Moreau JF. Magnetic

[23] Roy C, Balzan C, Thoma V, Sauer B, wattiez A, Leroy J. Efficiency of MR imaging to

[24] S. C. Modessitt, G. Tortolero-Luna, J. B. Robinson. D.M. Gerhenson, J.K. Wolf Ovarian

[25] Mc Meekin DS, Burger RA, Manetta A, Di Saia P, Barman ML. Endometrioid

[26] M Takeuchi, K Matsuzaki, H. Uehara, H. Nishitani. Malignant transformation of Pelvic

endometriosis or adenomyosis?. Fertil and Steril. 1998; 69: 972-974.

Feb;162(2):315-8.

Radiology. 2004 Aug;232(2):379-89

imaging. Radiology 1991. 180: 73-78.

Gynecologic Laparoscopy 2002; 9 (1) 15-23.

MR imaging. Radiology 1989; 171:693–696

Gynecologists Vol. 100, No. 4, October 2002 788- 794

61.

456.

451.

vol 11 no.9 2014-17.

Apr;14(4):1080-6.

1995; 59:81-86

2006; 26:407-417

Imaging 2008; XX:1-9.

Torizuka K, Ozasa H. Endometrial cysts of the ovary: MR imaging. Radiology. 1987

endometriosis: MR imaging features. AJR Am J Roentgenol. 1994 Aug;163(2):357-

endometriosis: MR imaging for diagnosis and prediction of extension of disease.

Nodular endoimetriosis: dynamic MR imaging. Abdominal Imaging 2007, 32: 451-

Comparison of Magnetic Resonance Imaging and Transvaginal Ultrasonography in diagnosing bladder endometriosis. The journal of the American Association of

uterosacral ligament origin and insertion points by magnetic resonance imaging. The American College of Obstetricians and Gynecologists. 2004; vol 103, no. 3, 447-

uterosacral ligaments by transrectal ultrasonography. Human Reproduction 1996;

resonance imaging characteristics of deep endometriosis. Hum Reprod. 1999

orientate surgical treatment of posterior deep pelvic endometriosis. Abdom

and Extraovarian-Associated Cancer The American College of Obstetricians and

adenocarcinoma of the ovary and its relationship to endometriosis. Gynecol Oncol.

Endometriosis: MR Imaging findings and pathologic correlation. Radiographics

Endometriosis is a common but complex gynecological disorder of unknown pathogenesis. It is characterized by ectopic growth of endometrial tissues. Based on Sampson's classical implantation theory, retrograde menstruation, immune escape, adhesion, angiogenesis and growth of endometrial cells are essential milestones in the pathogenesis of endometriosis. The cellular communications of immune, endothelial and endometriotic cells during endometriosis development are mediated via cytokines and chemokines. Many specific cytokines in peritoneal fluid of patients with endometriosis are aberrant from normal women. However, it's not clear at which stage of endometriosis these aberrant cytokines begin to change and owing to the limitation with human study the functions of these cytokines were only investigated in vitro. On the other hand, the onset of angiogenesis is initiated by oxidative stress due to cellular and tissue hypoxia, which is mainly coordinated by the hypoxiainducible factors (HIFs). HIFs stimulate VEGF transcription and activation in endometriosis lesions in acquiring new blood vessels for survival and growth. Monitoring inflammatory response, oxidative stress and angiogenesis in the endometriosis lesions is of vital importance in understanding the pathophysiological changes during early development of endometriosis.

In our studies, we investigated for the first time the dynamic changes of oxygen reactive species and angiogenesis in the endometriosis implants by in vivo imaging techniques and characterized regulation of cytokines, hypoxia and angiogenesis factors within the first 24 hour of experimental endometriosis in mice. We identified significant oxidative stress and hypoxia responses in the endometriosis implants in early phase only, but specific estrogen-dependent cytokine activations and angiogenesis signaling in late phase. In this chapter, we will describe the non-invasive in vivo imaging method as a valuable tool for monitoring oxidative stress and angiogenesis in endometriosis and to understand its role in the early development and growth of endometriosis. We will also demonstrate oxidative stress preceded hypoxia and cytokine activation and angiogenesis signaling in the pathogenesis of early endometriosis.
