Mammography and ultrasonography, long the cornerstones of women’s imaging, are increasingly being joined by other modalities, as either supplements or substitutes. Moreover, the issues in women’s imaging have extended beyond the female organs. This article summarizes current and emerging practices in 2003.

Breast Imaging

Breast ultrasonography, which has been employed primarily to distinguish a cyst from a solid mass, is becoming more important as an adjunct to diagnostic x-ray mammography. Doppler ultrasonography is able to differentiate postoperative and postradiation scarring from residual or recurrent cancer. In women with palpable infiltrating ductal cancers, ultrasonography during breast-conserving surgery can reduce the need for second operations by defining the limits of the tumor.1

Because of its high false-negative and false-positive rates, ultrasonography has little role at present in general screening for breast cancer.2 However, in high-risk women with dense breasts, an argument has been made that imaging should be performed every 6 months, alternating ultrasonography and mammography to provide close follow-up with a lower radiation dose.3 Screening of high-risk women may also be improved by a computer program that acquires images every 800 ?m and creates a cin? loop for image analysis. In the initial series, 18 of the 20 confirmed cancers were found in this way versus 15 by mammography, and the positive biopsy rate was 60%.4

Because of their high vascularity, nearly all primary breast cancers are detectable with gadolinium-enhanced MRI.5 Today, breast MR is indicated for identifying multiple or bilateral tumors and chest wall involvement after one breast cancer has been found, assessing the extent of a lobular carcinoma, locating an occult primary tumor, monitoring neoadjuvant chemotherapy, and distinguishing scar from recurrent tumor.5 Some centers, particularly in Europe, perform MR before breast-conserving surgery to reduce the reoperation rate.

Use of MRI for breast cancer screening is hampered by its cost, inconvenience, and poor specificity secondary to enhancement of many benign lesions such as fibroadenomas.5 Nevertheless, like ultrasonography, it may have a place in screening young women with a particularly high risk of breast cancer. In one trial, MRI found six invasive cancers among 196 such women, whereas mammography detected only two and ultrasonography three.6 Clinical trials of MRI for this indication are in progress in North America and Europe.

Various nuclear medicine techniques are helpful as problem-solving tools in breast imaging. Among patients with minimal mammographic and clinical abnormalities, 27 of the 30 confirmed cancers, including 11 lesions < 1 cm, were identified by 99mTc-sestamibi scintimammography.7 Other studies confirm the utility of scintimammography both for determining the nature of a breast lesion and for identifying local metastases.8,9 Planar and single-photon emission tomography offer the opportunity to use disease- or tissue-specific imaging agents such as labeled receptor-binding ligands and monoclonal antibodies to characterize lesions.10 Positron emission tomography (PET), which may be the most sensitive and specific means of characterizing breast lesions, is not widely used for this purpose because the same information can be obtained less expensively by biopsy. However, PET is valuable in determining a patient’s prognosis and monitoring treatment. In advanced breast cancer, the response to chemotherapy can be predicted with high accuracy by PET after the first course of drugs is given.11,12 Women whose tumors are drug resistant can thus be spared further toxicity. Under development are scanners specifically for breast imaging and cameras that can attach to mammography machines to make the use of PET in the breast easier.

Uterine Imaging

In premenopausal women, the most common causes of uterine bleeding are adenomyosis and fibroids. In postmenopausal women, endometrial carcinoma also must be considered in the differential diagnosis. Until recently, the differential diagnosis required a biopsy, but the conditions now can often be distinguished by transvaginal ultrasonography. If carcinoma is found, measurement of endometrial volume with three-dimensional ultrasonography may be helpful in characterizing it, as larger tumors tend to be poorly differentiated whereas smaller tumors generally are well differentiated.13 Gynecologists at Ioannina University Hospital in Greece, who compared transvaginal ultrasonography and biopsy in 80 consecutive perimenopausal women with uterine bleeding, found that if a 13-mm thickness of endometrium was defined as the upper limit of normal, the sensitivity of ultrasonography for endometrial disease was 100%. Those investigators suggested using ultrasonography to determine which patients truly need invasive diagnostic procedures.14 Danish investigators made a similar suggestion, although they cautioned that this and other imaging techniques “may yield highly idiosyncratic results when used by inexperienced staff, and efforts should be made to reduce such observer variation.”15 If endometrial cancer is identified and confirmed, contrast-enhanced MRI allows assessment of the extent of the tumor and the likelihood of invasion, thus helping in treatment selection.16

St George’s Hospital Medical School in London has established a one-stop clinic for women with abnormal uterine bleeding at which the basic work-up includes transvaginal sonography and sonohysterography with saline contrast.17 A diagnosis can be made with a single visit in most patients, and inpatient hysteroscopy, the initial procedure at many medical centers, is seldom necessary. St George’s also maintains an infertility clinic where, again, ultrasonography is the foundation of the work-up. The accuracy of this study is at least as good as that of more expensive procedures such as laparoscopy and MRI.18 Patients find ultrasonography very acceptable, and the study has been cost-effective in the hospital’s experience.

Adnexal Imaging

The first question to be answered about an adnexal mass is whether it is benign or malignant. Both ultrasonography and MRI are good at identifying a mass as benign but less specific for cancer.19 Three-dimensional power Doppler ultrasonography may be able to identify ovarian cancer by measuring the resistive index of the blood vessels,20 although the technique is still investigational. If a mass is known to be malignant, imaging is called on to identify local and regional spread and to determine whether any lesions are likely to be unresectable.21 Either CT or MRI is more accurate in staging advanced ovarian cancer than is ultrasonography.22

Women at high risk of ovarian cancer present an important problem in early detection. Only half of these tumors can be identified by ultrasonography when they are in stage I, and use of ultrasound screening outside an investigational setting is not advised.23 The National Cancer Institute is evaluating possible new markers for this cancer.

Imaging in Pregnancy

Ultrasound scans have been advocated to identify unrecognized pregnancy in trauma victims before exposing them to x-rays,24 to diagnose ectopic pregnancy, and to determine whether a woman is at risk of premature delivery.25

Fetal scanning to identify birth defects is a popular use of ultrasonography, although some have questioned its accuracy and cost-effectiveness.26,27 Three-dimensional sonograms are superior in identifying several fetal abnormalities and may help families to understand their nature. Also, because they present the fetus in a form recognizable to lay people, three-dimensional images may encourage the pregnant woman to refrain from harmful behaviors such as smoking. However, in view of its higher cost, many commentators question whether routine three-dimensional prenatal ultrasonography is justified. If further study is needed to diagnose or define an abnormality, MRI is the preferred modality.28

Cancer Staging

The trend to minimally invasive treatment of smaller (<3 cm) primary breast cancers has been accompanied by a reluctance to dissect the axillary lymph nodes routinely. Since the mid 1990s, there has been a rapid shift to identifying and examining the likely first landing site for metastases (sentinel lymph node), with further dissection depending on whether cancer is found there. The dye isosulfan blue and 99mTc sulfur colloid have been the most popular targeting agents, with some investigators arguing that both should be used,29 especially when a department is just beginning sentinel node identification.30 An experimental Tc-labeled monoclonal antibody against human milk fat globule 1 has shown a specificity of 93% and a positive predictive value of 92%.31 European oncologists tend to perform preoperative lymphoscintigraphy if 99mTc is used, whereas American surgeons generally locate the sentinel node only by intraoperative use of a gamma probe. Positron emission tomography with 18 fluorine deoxyglucose has excellent specificity but low sensitivity.32

Sentinel node analysis is not universally accepted. Michael A. den Bakker and colleagues of Erasmus Medical Centre in Rotterdam found metastases in nonsentinel nodes in 11 of 32 women, with no correlation being apparent between such metastases and the stage or grade of the primary tumor. Those investigators therefore argued that even women with low-grade stage T1 primary tumors require a full axial dissection.33 M. T. Nano and associates of the Royal Adelaide Hospital Cancer Centre in South Australia, who support sentinel node analysis, nevertheless found two women among 285 who “may have had their management and survival prospects…jeopardized owing to a false-negative sentinel node,”34 and M.A. Chung and coworkers of the Breast Health Center in Providence, RI, observed three axillary recurrences during a median follow-up of 206 women who had negative sentinel nodes.35

Sentinel node sampling is being explored for some gynecologic cancers. Pelosi and associates of the Ospedale S Giovanni Batista in Turin, Italy, gave 99mTc and blue dye to 11 women before laparoscopy-assisted vaginal hysterectomy and used a gamma probe and visual examination intraoperatively to identify sentinel nodes.36 They described the method as “a very promising tool to transform the management of early-stage endometrial cancer.”

In patients with lymph node metastases, further evaluation for systemic metastases is necessary to direct treatment. Computed tomography is often the initial study, but PET is valuable to clarify inconclusive results and for restaging in cases of recurrent disease.37

Other Issues

Two important issues in women’s imaging are not related to the “female organs.” One is coronary artery disease, which is more difficult to identify in women because of differences in their body habitus, smaller hearts, greater likelihood of having atypical symptoms, and lower prevalence of classic obstructive lesions. Whereas only 17% of men referred for coronary angiography are not found to have significant stenoses, this is true of half of women.38 One result is the expenditure of more than $134 million annually without the finding of a treatable lesion.38 Exercise ECG, stress echocardiography, and gated 201-thallium SPECT likewise are less useful in women.39

In an effort to improve the imaging-based diagnosis of coronary artery disease in women, the National Heart, Lung, and Blood Institute organized Women and Ischemia Syndrome Evaluation (WISE), which enrolled 936 women from 1996 to 2000. Abnormal flow reserve was found to be common in women with chest pain, as is endothelial dysfunction, and that women have a higher prevalence than men of single-vessel disease.40 Myocardial perfusion imaging with 99mTc41 or gadolinium42 or echocardiography with harmonic imaging or a myocardial contrast agent has proved effective. In a woman with chest pain, either study can direct the patient to more invasive studies or, alternatively, to safe discharge from the emergency department, with significant cost savings.41 Another effective technique is determination of the ratio of phosphocreatine to adenosine triphosphate with 31P magnetic resonance spectroscopy. A reduced ratio is indicative of myocardial ischemia and a higher risk of major adverse cardiac events.39

The $3 billion-a-year market for absorbent pads and underwear is testimony to the prevalence of urinary incontinence. In the past, imaging usually was not part of the work-up. However, there is growing recognition that imaging can contribute to patient evaluation, in part because of its ability to define the prolapse that often accompanies incontinence. Perineal or translabial ultrasonography and dynamic fluoroscopy have been used, but MRI has a growing role because of its excellent depiction of the soft tissues.43 MRI is particularly helpful in identifying the anatomic cause of incontinence and determining the cause of surgical failure.44

Imaging for Treatment Guidance,UFE

Considered an experimental procedure when it was broadcast live from a nearby hospital into a general session of the Cardiovascular and Interventional Society of Europe Conference in London, UK, in 1997, embolization is an increasingly popular treatment for uterine fibroids, particularly in younger women who want to remain fertile. The procedure itself requires angiography, but many interventionalists perform preoperative imaging to look for signs of malignancy or anatomic features that would make embolization undesirable. According to a team from the Mallinckrodt Institute of Radiology at Washington University in St Louis, “ultrasound and magnetic resonance imaging are vital elements” of work-up and treatment planning.1 Imaging also is helpful in follow-up. Tranquart and associates of the CHU Bretonneau in Tours, France, monitored 58 women for 3 to 24 months after embolization. All but two of the procedures were successful. At 3 months, size of fibroids had declined an average of 29%; by 24 months, they had shrunk an average of 86%. All intrafibroidal blood vessels were ablated by 3 months in most patients, but there was no change in the uterine vasculature at any time.2

Intensity-Modulated Radiation Therapy

Intensity-modulated radiation therapy (IMRT) is intended to reduce the dose delivered to normal tissues in the vicinity of the tumor. Arno J. Mundt, MD, and colleagues of the Department of Radiation and Cellular Oncology at the University of Chicago treated 40 women with gynecologic cancers by IMRT.3 A contrast-enhanced CT scan was used to define the clinical target volume, and a 1-cm border was drawn to produce the planning target volume (PTV). Commercial software was used to develop a 7- or 9-field treatment plan. On average, 98% of the PTV received the prescribed dose. There were no instances of Grade 3 or 4 genitourinary or gastrointestinal radiation toxicity. Grade 2 gastrointestinal toxicity was reported by 60% of the patients, whereas among 35 women previously treated with a standard radiation therapy protocol, this figure was 91%. Similarly, Grade 2 genitourinary toxicity was seen in 10% of the IMRT patients and 20% of the conventionally treated patients. The IMRT method also has been used as part of breast-conserving therapy for patients with pectus excavatum.4

-Judith Bronson

Judith Gunn Bronson, MS, is a contributing writer for Decisions in Axis Imaging News.


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