This chapter should be cited as follows: First Published April 2009
Zaher, S, Regan, L, Glob. libr. women's med.,
(ISSN: 1756-2228) 2009; DOI 10.3843/GLOWM.10451

Benign gynecology

Magnetic Resonance-guided Focused Ultrasound for Uterine Fibroids

Summia Zaher, MD
Department of Obstetrics and Gynaecology, Imperial College Healthcare NHS Trust, St Mary’s Hospital, London W2 1NY, UK
Lesley Regan, MD, FRCOG
Department of Obstetrics and Gynaecology, Imperial College Healthcare NHS Trust, St Mary’s Hospital, London W2 1NY, UK


Uterine leiomyomata are the most common pelvic tumor in women, accounting for up to one in three gynecology clinic referrals. Although they are usually referred to as fibroids, these tumors consist of uterine smooth-muscle tissue, enriched with fibrous extracellular matrix.1 In some cases, fibroids appear to originate from smooth-muscle cells of the uterine blood vessels.2

Macroscopically, these tumors are firm and round, or oval in shape. Microscopically, they are composed of smooth-muscle bundles in a whirl-like pattern, well circumscribed but not encapsulated. Of importance in therapy is that they are often highly vascular. They can occur singly, but more usually, there are multiple fibroids in the same uterus of varying dimensions and location.


The prevalence of clinically symptomatic fibroids peaks toward the end of a woman’s reproductive life and declines after menopause.3 Most women with uterine fibroids do not seek specific therapy, but some 25% of women of reproductive age experience symptoms that necessitate them seeking treatment.2 There appears to be a genetic predisposition to uterine fibroids as they are particularly common in Afro-Caribbean women, with a three-fold increase in incidence compared to that in Caucasian women. Furthermore, the clinical symptoms of Afro-Caribbean women tend to be more severe at presentation.4

Although uterine leiomyomata affect the reproductive health and well-being of approximately 25% of premenopausal women, risk factors are poorly understood. Elevated adult body mass index (BMI) is associated with a modest increased risk of uterine leiomyomata among premenopausal women,5 as is a familial tendency to develop fibroids. Parity appears to reduce risk and this risk is further reduced with increasing parity.6 The presence of fibroids is more common in women who consume red meats, whereas a high intake of green vegetables seems to have a protective effect.7 Elevated diastolic blood pressure may increase fibroid risk through uterine smooth muscle injury, not unlike atherosclerosis. In a 10-year prospective follow-up study of 104,233 premenopausal nurses with no history of cancer or fibroids at enrollment, elevated blood pressure exerted an independent increase in risk of clinically detectable fibroids.8

The Black Women’s Health Study is a US prospective cohort study of black women who completed biannual mailed health questionnaires from 1997 through 2001. Among black premenopausal women with intact uteri and no prior diagnosis of uterine leiomyomata, high BMI, and weight gain exhibited a complex relation with risk for uterine leiomyomata. Interestingly, weight gain was positively associated with risk among parous women only.9

This study also noted a positive association with current consumption of alcohol, particularly beer, but found that cigarette smoking and caffeine consumption were unrelated to overall risk.10 After adjustment for age, BMI, smoking, and alcohol intake, the risk of leiomyomata (confirmed by ultrasound or at hysterectomy) was inversely associated with age at menarche, parity, and age at first birth, and positively associated with years since last birth. Overweight or obesity appeared to attenuate the inverse association between parity and uterine leiomyomata. Current use of progestin-only injectables was inversely associated with risk. No consistent patterns were observed for other forms of hormonal contraception.11


The etiology and pathogenesis of fibroids remains unclear. The theory that fibroids are steroid dependent is supported by observations that they decrease in size at the menopause and during other hypoestrogenic conditions such as down-regulation treatment with gonadotropin-releasing hormone (GnRH) agonists.12 Although estrogen has been implicated as the dominant hormone, progesterone has also been reported to have a role in the growth of fibroids. However, whether it is estrogen or progesterone that exerts the most important influence on fibroid growth remains a contentious issue.13


Fibroids are classified by their location within the uterus. Leiomyomas may be subserosal, submucosal or intramural and frequently occur at multiple sites. Subserosal fibroids on the external surface of the uterus may be sessile or pedunculated. This type of fibroid is the easiest to remove laparoscopically. Submucous myomas which project into the endometrial cavity may be removed by hysteroscopic resection. Intramural leiomyomas in the myometrial wall of the uterus may both distort the uterine cavity and/or cause an irregular external uterine contour. Historically, these lesions have usually required open pelvic surgery.


Fibroids present with a variety of symptoms depending on their size, location, and the reproductive status of the woman. Typically they cause abnormal uterine bleeding, pain, and pelvic pressure symptoms.14

The most common type of abnormal bleeding associated with leiomyomas is menorrhagia or polymenorrhea, prolonged or excessively heavy menstruation.15 The heavy bleeding frequently results in iron deficiency anemia and the frequent change of tampons or pads may cause a significant disruption to the woman’s lifestyle.

Acute pain is rare, but can occur in situations where there is degeneration of the fibroid due to an insufficient blood supply; so called red degeneration, which may occur during a pregnancy. Acute pain may also be due to torsion of a pedunculated fibroid or to cervical dilatation caused when a submucous fibroid prolapses into the cervical canal from the uterine cavity.

Pelvic pressure symptoms are caused by enlargement of the uterus by the fibroid mass. The pelvic and abdominal discomfort may be similar to the discomfort women experience during pregnancy. If neighboring structures are compressed by the fibroid this may lead to difficulty with urination in the case of an anterior fibroid or problems with defecation and dyspareunia in the case of a posterior wall fibroid.


The diagnosis of uterine fibroids is based on the clinical history and examination. Typically the patient presents with a gradual increase in abdominal size, heavy but regular periods, and a negative pregnancy test. Other causes for an increased abdominal girth include adenomyosis and ovarian pathology. It is difficult to differentiate between these by abdominal palpation alone, and therefore radiological examination is required for confirmation. Ultrasound may be used to confirm the diagnosis and exclude other conditions (Fig. 2). Transabdominal or transvaginal ultrasound is a sensitive tool for the detection of an enlarged uterus, but identification of the precise location of the fibroids is dependent on the expertise of the operator.

Fig. 2. Ultrasound image of uterine fibroid.


Magnetic resonance imaging (MRI) has gained widespread use and popularity for use in pelvic imaging. It is noninvasive and safe, with no radiation effects, a particularly important consideration for younger women. The multiplanar sequences allow differentiation of the substructure of the uterus, cervix, vagina, and ovaries (Fig. 3). MRI allows the radiologist to differentiate uterine anatomy and localizes pelvic pathology with precision. The routine use of both T1- and T2-weighted (T1W and T2W) sequences, before and after the injection of intravenous gadolinium, provides further information on specific characteristics of the fibroid and optimizes the soft tissue contrast available with MRI.

Fig. 3. MRI of normal uterus.



MRI offers special advantages for the imaging of fibroids. It confirms the diagnosis, provides accurate size and volume measurements ,and also characterizes the fibroids into hyperintense or hypointense, according to how vascular they are. By using intravenous contrast, the perfusion and therefore presence of necrosis and degeneration can also be determined (Figs. 4 and 5).

Fig. 4.  MRI T2 weighted sagittal image of multiple uterine fibroids.



Fig. 5. MRI T2 weighted sagittal image of hyperintense fibroid.




Uterine myomas can generally be managed expectantly unless they are causing symptoms. Historically, where treatment is warranted, surgery has been the mainstay – either myomectomy or hysterectomy.16 However, recent changes in cultural attitudes together with an increase in maternal age at childbirth have resulted in women becoming increasingly reluctant to undergo open pelvic surgery. During the past decade societal changes have led to a decline in  hysterectomy rates and an increased uptake of nonsurgical interventions such as the Mirena IUS and uterine artery embolization. However, many women find the unpredictable bleeding pattern associated with the Mirena coil to be unacceptable and the safety of uterine artery embolization women in wishing to preserve their fertility is debatable.17 As a result, the need for a noninvasive, fertility friendly solution to the treatment of fibroids has arisen.


The ability of ultrasound energy to interact with biologic tissues has been recognized for many years. The earliest medical uses of ultrasound were therapeutic rather than diagnostic, and the ability of ultrasound energy to cause a rise in tissue temperature was recognized as long ago as 1927.18 Limitations of accuracy and temperature monitoring have hampered clinical development of this technique until the recent introduction of modern image guidance. The feasibility of an MRI guided system was first described in 1995.19 High intensity ultrasound can be focused into a small volume to produce a rise in tissue temperature sufficient to cause lethal cell damage in the target at depth within the body.20 Concurrent MR imaging allows accurate tissue targeting and real-time temperature feedback, thereby achieving controlled localized thermal ablation without causing damage to surrounding tissues. Focused ultrasound energy holds the promise of not just minimally invasive, but a completely noninvasive, low-risk therapy for treating uterine fibroids. Using this technique, complete areas of tissue within a solid organ can be destroyed without breaching the skin.

Our fibroid center at St Marys’ Hospital, London, UK, was one of the first in the world to be involved in the clinical development of a focused ultrasound treatment modality. The Exablate 2000TM (Insightec, Haifa, Israel) fully integrates with our standard closed 1.5 tesla MRI system. A specially integrated patient bed containing an ultrasound transducer, upon which the patient is positioned supine, is used. An ultrasound beam is generated from the phased array transducer which travels through a gel pad and water bath, all helping to create acoustic coupling (Fig. 6). The ultrasound travels easily through the skin and propagates through the tissue focusing at a specific target within the body. The tissue at the focus reaches temperatures sufficient to cause cell coagulation. It is important to remember that there is no damage to adjacent tissue and only the target tissue undergoes necrosis.

Fig. 6. Patient positioned prone, with abdomen placed in a waterbath containing the gel pad.




Concurrent MR imaging allows:

  •     Three dimensional anatomic information for exact tumor targeting
  •     Beam path visualization for safe treatment
  •     Real-time MR thermometry to achieve planned outcome
  •     Posttreatment contrast imaging for evaluating treatment outcome.

This closed loop therapy concept provides the operator with immediate feedback, the ability to react to that feedback and immediate knowledge of the outcome of therapy. This provides the clinician with total control of the procedure, thereby ensuring both safety and efficacy.



There are several reasons why uterine fibroids are well suited to treatment with MRgFUS. Fibroids are generally well defined and clearly seen on MRI. They are rich in extracellular matrix, which makes them relatively easy to target with thermoablative energy.

The MRI employed before, during, and after this therapy helps in screening and patient selection as well as in the evaluation of treatment outcome. Objective measurements of volume reduction can be made and since studies have suggested that the nonperfused volume correlates with treatment outcome, another objective predictor of treatment success is provided.21 The only validated measure of fibroid symptomatology, the uterine fibroid specific quality of life questionnaire (UFS-QOL), can be used to measure treatment success in terms of symptom improvement, as determined by the patient.22



To date over 400 women have taken part in formal multicenter international research trials and since FDA approval was granted for commercial treatments in 2004, globally over 4000 women have been treated.23 The FDA approved the system based on a review of clinical studies of safety and effectiveness conducted by the manufacturer and on the recommendation of a panel of outside experts convened by the agency to review the device.

The original goal of the first study was to ensure safety of the treatments, while investigating the level of efficacy possible. As such, restrictions were placed on the volume of fibroid tissue that could be treated in any patient. This study compared the results of 109 women who underwent MRgFUS with those of 82 women who had a hysterectomy at seven medical centers around the world, including our unit at St Mary’s. Only nine adverse events were reported, including pre-existing medical conditions and continued heavy menses. There was only one device-related adverse incident, with a patient experiencing leg numbness which spontaneously resolved. When the MRgFUS-treated women were reviewed 6 months later, 79.3% reported successful reduction in fibroid-related problems. The mean reduction in fibroid volume was 13.5%.24

Having established the safety of the MRgFUS device and the fibroid ablation procedure, the FDA expanded the allowable treatment volume. The Continued Access Study followed 160 women of whom 96 were treated under the original restricted treatment guidelines and 64 women were treated under the expanded treatment guidelines. In the latter group, 84.6% of women experienced significant symptomatic improvement at 24 months posttreatment versus 76.2% in women treated under the original guidelines. This study concluded that MRgFUS treatment results are consistent and reproducible. Furthermore, the expanded treatment guidelines demonstrated that the greater the volume of tissue treated the greater the symptomatic improvement.21

In summary, for women in whom nonperfused volumes of 60% and over are achieved, only 11% will require alternative treatments at 24 months.21


Initial research exclusion criteria dictated a maximum fibroid diameter of 10 cm because the time required to perform the procedure is volume dependent. This limitation had important clinical implications, since fibroids may be asymptomatic until this size threshold has been crossed, particularly amongst black women in whom presentation at a younger age with larger fibroids is common.25 Our team at St Mary’s undertook the GnRH large fibroid study, where we postulated that by administering GnRH agonists to effect a temporary shrinkage in fibroid volume, prior to carrying out MRgFUS, that we could extend this innovative treatment to a much wider patient group. This was a prospective study, with a 12-month follow-up. Women received a 3-month course of GnRH agonist treatment followed by MRgFUS treatment. The primary outcome measurement reported was a change in symptom severity score (SSS) as judged by the Uterine Fibroid Symptoms and Quality of Life Questionnaire (UFS-QOL). Comparison was made at enrollment, treatment, and at 3, 6, and 12 months posttreatment. A secondary outcome was the measured change in target fibroid volume. Fifty women were enrolled in the study. There was a 50% reduction in mean SSS at 6 months and 48% at 12 months posttreatment with 83% of women achieving at least a 10-point reduction in symptom scoring (p<0.001). There was an average reduction in target fibroid volume of 21% overall at 6 months (p<0.01) and 37% at 12 months (Fig. 7). No serious infective complications or emergency operative interventions were reported/occurred.25

Fig. 7. MR images pre GnRH, post GnRH, and posttreatment.

The initial FDA recommendation was that only women who had completed their families should be treated with MRgFUS. However, following consistently good safety and efficacy results being reported, multicenter fertility studies were commenced and are on-going. These studies are actively recruiting women with symptomatic uterine fibroids who wish to become pregnant. The non-invasive nature of ExAblate, whereby only the uterine fibroids undergo thermal ablation with no damage to healthy surrounding tissue, suggests that MRgFUS should be a safe approach for women who want to preserve their fertility. The initial results have been very promising and evidence is accumulating to suggest that women are able to conceive promptly and successfully deliver children after undergoing MRgFUS treatment for their uterine fibroids.26, 27

To date, 28 women have delivered healthy infants at term without complications and further pregnancies are ongoing. Eighteen women have delivered vaginally and ten by cesarean section. Most importantly there were no cases of uterine rupture, preterm labor, placental abruption, abnormal placentation, or fetal growth restriction – the mean birth weight being 3.4 kg. These results suggest that MRgFUS treatment has the potential to deliver safe and effective treatment for uterine fibroid symptoms without damaging patient fertility or creating additional pregnancy related risks. Accordingly the Conformitee Europeene  (CE) marking for the ExAblate system has been changed to include patients wishing to preserve their fertility.



Adenomyosis is a common benign gynecological disorder affecting premenopausal women, which is characterized by the growth of ectopic endometrial glands and stroma deep within the myometrium.28 The "benign invasion of endometrium into myometrium" that occurs in adenomyosis can lead to enlargement of the uterus, reactive hyperplasia ,and hypertrophy of the neighboring myometrium.29 Adenomyosis  can be found in up to 30% of hysterectomy specimens.30

Symptoms of adenomyosis include menorrhagia, dysmenorrhea, and diffuse uterine enlargement, which may result in pelvic pressure effects. The severity of symptoms correlates roughly with the extent of disease.31 Clinically, adenomyosis is difficult to distinguish from uterine leiomyoma, since the symptoms are similar and the two pathologies are poorly distinguished by ultrasound. MRI is currently regarded as the best imaging tool for the differential diagnosis of leiomyomas and adenomyosis.32

Based on our experience in some patients with combined disease, in whom we have successfully ablated both leiomyomatous and adenomyotic lesions, we hypothesize that MRgFUS can also treat adenomyosis successfully without damaging the surrounding myometrium and hence does not compromise subsequent fertility.


In summary, MR-guided focused ultrasound treatment of uterine fibroids has been shown in phase I, II, and III clinical trials to be a safe treatment option. Efficacy, in terms of sustained symptomatic relief, correlates with the volume of fibroid ablation, and recent trials with adjuvant GnRH analogues prior to treatment have demonstrated efficacy in patients with larger fibroids, thus increasing the eligible patient population.  Collectively these studies should secure a place for MRgFUS as a valid alternative to current therapies.

The non-invasive nature of the MRgFUS procedure holds particular attraction for patients who wish to become pregnant in the future. Currently available data are encouraging; with published case studies suggesting that fertility is not impaired and that pregnancies following MRgFUS are relatively uncomplicated, although more experience will be required before we can effectively counsel patients of reproductive age. The National Institute of Clinical Excellence (NICE) has recently published guidelines which recognize MRgFUS as a treatment alternative for symptomatic fibroids and has encouraged our ongoing research program.



The authors of this chapter are grateful for support from the NIHR Biomedical Research Centre Funding Scheme. 




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