X-ray techniques

Standard radiographs are obtained by placing the patient between an X-ray source and a photographic film. Images are produced by the attenuation of X-ray photons by the patient. As a result, structures of interest are often obscured by the attenuation of photons by other overlying structures. A basic limitation of the standard X-ray technique is the effect of scattered photons adding to the image noise and degrading the quality of the final image. Various manoeuvres have been adopted to reduce this effect, such as scatter grids. The linear tomograph is obtained by the synchronous movement of the X-ray tube and the film, causing a blurring of the overlying and underlying structures while leaving the plane of interest in focus. This procedure increases the detection of lesions such as chest metastases.

Contrast studies

To increase contrast in the soft tissues, an iodine-containing agent may be injected into the lumen of a cavity such as the uterus and fallopian tubes (hysterosalpingogram) or blood vessels (angiogram). Such contrast agents are widely available in ionic and (more expensive) non-ionic forms. The less toxic non-ionic preparations are preferred.

Ultrasound

In Glasgow in 1950, Ian Donald used an industrial flaw detector, designed for testing the integrity of steel boilers, to demonstrate that the massive abdominal swelling of one of his patients was fluid and not solid (Kurjak 2000). A large ovarian cyst that proved to be benign was subsequently removed. Since then, the rapid and continuing evolution of ultrasound technology has led to a proliferation of applications in almost all aspects of medicine and surgery.

Ultrasound waves are generated by a piezoelectric crystal mounted in a transducer housing, and the whole construction is referred to as a ‘probe’. Piezo materials respond to an applied voltage by changing thickness, and produce electrical signals of a few millivolts when compressed. In the final image, the resolution along the beam is determined by the wavelength, while the resolution across it depends on the width of the beam, which is improved by focusing using combinations of lenses and electronic mechanisms.

The time from transmission of the ultrasound pulse to receipt of an echo is translated into depth using the speed of sound in tissue. Echoes arise wherever the pulse of ultrasound encounters an interface between tissues of different acoustic impedance, which may simplistically be regarded as changes in density. Thus, homogeneous materials such as clear fluids are echo-free, while low-level echoes are given by the interfaces between the various components of soft tissue structures. Stronger echoes result from the interface between fibrous tissues (high impedance) and fatty tissues (low impedance), and maximal echoes are given by interfaces between soft tissues and bone or gas, both of which are effectively opaque to ultrasound. To form a real-time image, the beam is electronically swept through a region of tissue and the images are pie-shaped (sector and curved arrays) or rectangular (linear probes).

The choice of frequency is a compromise between the spatial resolution and the depth of penetration required. The higher the frequency, the better the resolution, but the greater the attenuation of the beam within the tissues. Hence, for abdominal scanning, frequencies of between 3.5 and 5 MHz are commonly employed. Probes designed for intracavitary and intraoperative use employ higher frequencies (8–15 MHz) because the organs of interest are closer to the transducer. This enables higher resolution images to be obtained, and also allows study of the movement of structures when pressure is applied to the probe, which gives important diagnostic clues on their relative mobility. The drawbacks of transvaginal scanning are practical (intolerance of the probe by the very young and old, and in the presence of scarring) and diagnostic (the depth of view is limited to approximately 70 mm) (Bennett and Richards 2000). By sweeping an array through the tissues, a three-dimensional scan can be created; while most useful in obstetrics to visualize complex structures such as the fetal face, it also displays uterine anatomy well (Alcazar and Galvan 2009).

The interactivity of ultrasound is an important feature; it is effectively an extension of clinical examination. Ultrasound also provides numerous views during the real-time examination and facilitates guided needle biopsies. However, it has many limitations, notably the variable image quality, that frustrate its application. An important problem is the complete barrier posed by bowel gas, which is why a full bladder is required for transabdominal scanning.

Doppler operates by detecting the change in frequency of ultrasound echoes caused by movement of the target. In the simplest system, this is done continuously with only minimal control of the beam direction. Continuous wave Doppler is well suited to fetal heart monitoring, especially because movements of the fetus do not interrupt the signal. In gynaecology, the vessels of interest are small so precise placement of the Doppler sample is a prerequisite. This can be achieved with pulsed Doppler. The Doppler gate is superimposed on a real-time image that allows the target to be pinpointed (Figure 5.1). The Doppler signal depicts a range of blood velocities occurring in the selected vessel over time. Output can be audio or as a strip chart on which intensity indicates the strength of the signal at each velocity in the spectrum. A variety of measurements can be made from these tracings, the most useful of which are systolic/diastolic velocity ratios. These are measures of the arteriolar resistance to flow, with a low value indicating low vasomotor tone, typical of the placenta and the corpus luteum. This pattern also occurs in inflammation and malignancy. High indices are typical of inactive tissue, such as the resting uterus. Doppler can be used to measure fetal and uteroplacental blood flow, thereby producing physiological information (Brinkman and Wladimiroff 2000).

Figure 5.1 Spectral Doppler. In this scan of an ovarian cancer, the Doppler gate (arrow) has been positioned on the tumour. The spectral tracing is in the lower portion of the figure and shows the typical low-resistance pattern of malignant neovascularization with marked diastolic flow.

In colour Doppler scanning, the same process is applied across an area of interest. The velocity signals are presented as a colour-coded overlay, superimposed on the real-time scan (Figure 5.2). Although the Doppler information is less rich than with spectral Doppler (only the mean velocity or the amount of flow is depicted), the angiogram-like map provides information on the morphological arrangement of the vascular tree, and its sensitivity allows vessels as small as approximately 1 mm in diameter to be detected. Colour Doppler is often used to locate a vessel to guide placement of the spectral Doppler gate for haemodynamic analysis.

Figure 5.2 Colour Doppler of an ovarian carcinoma. On colour Doppler, flow signals are colour coded and presented as an overlay on the grey-scale image in the left-hand panel of this transvaginal scan, while the right-hand panel shows the grey-scale image on its own. The neovascularization in this ovarian carcinoma is shown as knots of colour. Apart from providing a graphic display of vascularity, a useful feature of colour Doppler is to guide placement of the gate for spectral Doppler tracings.

A recent advance has been the introduction of contrast agents for ultrasound in the form of microbubbles for injection. Not only does the signal improvement they produce allow smaller vessels to be detected, but they can be visualized in grey scale to reveal regions of flow in real time. In addition, they can be used as tracers by tracking a bolus as it crosses a tissue of interest, and this may yield valuable functional information.

Computed tomography

The sensitivity of conventional radiography may be improved by using a radiation detector such as a scintillation crystal and a photomultiplier tube. By measuring the attenuation of a finely collimated beam of radiation, passing through the patient at multiple angles, it has been possible to produce images of very high quality. A computer uses the attenuation of each beam passing through the patient to calculate the attenuation coefficient for each area of tissue in the cross-section of interest. The final images are reconstructed using a filtered back-projection technique and displayed in grey scale as a series of attenuation units (with values between +500 and −500) in a matrix of 512 × 512 or 1024 × 1024 elements. The reconstruction of data is limited to the transverse (transaxial) plane. This imaging technique revolutionized modern medicine in the 1970s, but its impact on gynaecology has been less marked.

Magnetic resonance imaging

MRI depends upon the magnetic properties of certain atomic nuclei which, when placed within a magnetic field and stimulated by radio waves of a specific frequency, will absorb and then re-emit some of this energy as a radio signal. This phenomenon of nuclear magnetic resonance (NMR) was first described by Felix Bloch and Edward Purcell in 1946. NMR as a basis for an imaging technique was proposed some 30 years later by Lauterbur.

Nuclei possessing magnetic properties have an odd number of protons or neutrons. The charged particles are spinning, which causes them to behave as tiny bar magnets. If placed within a magnetic field, a majority of protons will line up in the direction of the magnetic field. In addition, their axes are tilted and caused to rotate like small gyroscopes. The frequency of this precessional movement is directly proportional to the strength of the applied field and is called the ‘Larmor frequency’. The hydrogen proton gives a relatively high signal due to its abundance in biological tissues. Other potential NMR isotopes include ¹³C, ²³Na, ¹⁹F and ³¹P.

If a pulse of radio waves is imposed on the nuclei, a strong interaction or ‘resonance’ will occur when the frequency coincides with the precessional frequency of the nuclei. The energy absorbed by the nuclei is then re-emitted as a signal that can be detected in a receiver coil situated around the sample. The initial strength of this signal is proportional to the proton density of the sample. It will then decay in an exponential fashion as the disturbed protons relax back to their original state. The T₁ relaxation time is described as the time taken for the stimulated protons to return to their initial state. The T₂ relaxation time is that taken for the precessing nuclei to get out of step with one another. A variety of sequences of radio wave pulses have been devised so that the resulting signal is weighted to different degrees by the proton density and the T₁ and T₂ relaxation times.

The contrast between different tissues in MRI can be manipulated by altering the pattern of radio waves applied. This is done by changing the time constants associated with the different sequences of radio waves: the repetition time, echo time or inversion time. A further advantage of MRI is the ability to obtain images in multiple planes, such as sagittal, coronal or oblique planes, without moving the patient.

The female pelvis is suitable for MRI examination because of the minimal effect of respiratory motion on the pelvic organs. By placing the receiver coil adjacent to the tissue of interest (e.g. endovaginally to maximize signal from the cervix), very-high-resolution images of an area of interest may be obtained. However, as the data to produce a set of images are accumulated over 5–10 min, patients are required to remain still during this time. If multiple sequences and multiple planes are employed, the total imaging time may exceed 30 min which reduces patient tolerance. However, newer faster pulse sequences with breath-hold techniques and improved computer software are greatly reducing scan times. Recently, open design MR scanners and production of MR-compatible equipment has produced an explosion in the field of ‘interventional MRI’. This has expanded the applications of MRI from being purely diagnostic to its use during treatment, such as for placing brachytherapy implants (Popowski et al 2000) or monitoring thermal ablative therapy.

Radionuclide imaging

Unlike the other imaging modalities, radionuclide imaging provides physiological rather than anatomical detail. Modern gamma cameras are capable of accurately imaging the distribution of administered radiopharmaceuticals, and the use of tomographic systems for single photon emission tomography has improved image resolution. In gynaecological oncology, radiolabelled monoclonal antibodies may be employed in the localization of malignancies (radioimmunoscintigraphy) and in their treatment (radioimmunotherapy).

The purity and specificity of monoclonal antibodies gives them an important role in tumour detection and possibly in the targeting of antitumour agents. Different anticytokeratin antibodies may help in distinguishing a primary ovarian adenocarcinoma from a metastatic adenocarcinoma, especially of colorectal origin (McCluggage 2000). These antibodies have also helped to clarify the origin of the peritoneal disease in most cases of pseudomyxoma peritonei. In recent years, several studies have also investigated the value of a variety of monoclonal antibodies in the diagnosis of ovarian sex cord stromal tumours, and in the distinction between these neoplasms and their histological mimics. Of these, anti-alpha-inhibin and CD99 appear to be of most diagnostic value (Choi et al 2000). Antibodies should always be used as part of a larger panel and not in isolation.

The antibodies or antibody fragments are radiolabelled with a gamma-emitting radionuclide such as ^99mTc, ¹³¹I, ¹²³I or ¹¹¹In. A subcutaneous test dose is no longer given because of the immune response it may generate in the patient. If ¹³¹I or ¹²³I is employed, oral potassium iodide is given to block thyroid uptake of free radioactive iodide. In addition, blood pool subtraction techniques are required for ¹³¹I studies to simulate the non-tumour distribution of labelled antibody. This is not necessary for ¹²³I- or ¹¹¹In-labelled preparations.

Following injection of the antibody, a gamma camera provides serial images of the distribution and uptake of radiolabelled antibody between 18 and 72 h after the antibody has been administered. The radionuclide ¹¹¹In is ideally suited for tomographic studies using images produced by a gamma camera mounted on a gantry which rotates through 360°. The images are reconstructed by computer in the same manner as X-ray CT. ¹¹¹In-labelled antibody is taken up into the liver, spleen, bone marrow and, occasionally, adrenal glands but is a more suitable radiolabel than ¹³¹I. Excretion of ¹¹¹In into the bladder has not been a problem, although non-specific bowel uptake may account for false-positive results. An example of an ¹¹¹In study is shown in Figure 5.3. A central area of increased uptake is apparent at the site of a primary ovarian cancer.

Figure 5.3 Radionuclide scan: primary ovarian carcinoma. Anterior view of the pelvis with 80 MBq ¹¹¹In-labelled OC-125.

¹⁸FDG (¹⁸fluorodeoxyglucose) is a non-specific positron-emitting tracer. It is an analogue of glucose, thereby reflecting metabolism and detecting the increased glycolysis associated with several tumour types. It gains entry into cells by membrane transporter proteins, such as Glut-1, which are expressed in many tumours. It is phosphorylated intracellularly to FDG-6-phosphate and retained within malignant cells. Tumour hypoxia may also increase ¹⁸FDG accumulation via activation of glycolysis. The quantitative parameter used is typically a standardized uptake value (SUV), which represents the tissue activity within a region of interest corrected for the injected activity and the patient’s body weight. A new lesion (Figure 5.4) or a rise in SUV within a lesion indicates disease progression. Whether this can be used as a marker for early therapy remains to be proven.

Figure 5.4 ¹⁸F positron emission tomography of a patient with cervical cancer showing metastatic deposits with increased glucose uptake in left axilla (short arrow) and right scapula (long arrow).

de Souza NM, Brosens JJ, Schwieso JE, Paraschos T, Winston RM. The potential value of magnetic resonance imaging in infertility. Clin Radiol 1995; 50(2):75–79, with permission of Elsevier.

Angiography

Diagnostic and therapeutic angiography have made great strides in recent years with the development of catheters whose tips can be manipulated. This allows considerable control over the guidance of these catheters into selected vessels. In parallel with this, ingenious devices have been devised which can be introduced via these catheters for purposes as diverse as angioplasty and embolization.

In gynaecological practice, the main use of angiography is the control of pelvic bleeding, but both the diagnosis of pelvic venous thrombosis and the prevention of subsequent pulmonary embolism are important roles for this exciting new technique. Pelvic arteriovenous malformations are most readily diagnosed and treated with angiography, and pelvic varices causing chronic pain may be managed in the same way. Selective sampling of gonadal venous blood and steroid hormone assay can be valuable in the preoperative assessment of phenotypic women with chromosomal abnormalities and intra-abdominal gonads of uncertain nature.

Normal anatomy and variations

Uterus

The normal uterine cavity is delineated as a triangular structure on hysterosalpingography, with the cornua and the internal cervical os as the corners. Intracavitary abnormalities, both congenital and acquired, such as internal septations and divisions may be defined using this technique (Figure 5.5). Similar information can be acquired with ultrasound following instillation of saline into the uterine cavity (hysterosonography) (van den Brule et al 1998).

Figure 5.5 Hysterosalpingogram: contrast outlining the cavities of a bicornuate uterus. Free spill into the peritoneal cavity can be seen on the right (arrow).

On ultrasound, the uterine cavity is normally represented by a bright line of apposition of the endometrial layers, although occasionally a trace of fluid can be seen at menstruation. Persistent fluid or fluid in a non-menstruating woman is abnormal. In adolescence, it may be caused by vaginal atresia, where the upper vagina dilates more than the uterus so that haematocolpos dominates the picture, while in postmenopausal women, cervical stenosis, either fibrotic or malignant, must be considered. Ultrasound is also useful in detecting the position of an intrauterine device; provided the coil lies in the uterus, it is easy to locate, but a coil that has penetrated through the myometrium is obscured by echoes from bowel gas (Figure 5.6).

Figure 5.6 Two views of an intrauterine device in the uterine cavity (arrows) with a coexisting pregnancy (arrowheads).

The entire uterus can be imaged using ultrasound (Figure 5.7) and its size measured accurately. This is useful in precocious or delayed puberty and in planning brachytherapy. The endometrium is seen as an echogenic layer of uniform texture, often with a fine echo-poor margin. Its thickness varies through the menstrual cycle from 12 mm premenstrually (double-layer thickness) to a thin line after menstruation. The endometrium gradually thins after menopause unless supported by hormones.

Figure 5.7 Transvaginal scan of the uterus. In this scan, taken in the luteal phase of the cycle, the secretory endometrium is seen as an echogenic band in comparison with the relatively echo-poor myometrium.

The morphology of the normal uterus, however, is best defined on MRI where its zonal architecture may be recognized (Hricak et al 1983). On T₂-weighted images, the endometrium is seen as a central high-signal stripe which increases in thickness in the secretory phase of the menstrual cycle. The inner myometrium (junctional zone) is of lower signal intensity than the outer myometrium on T₂ weighting, and correlates histologically with a layer of more densely packed smooth muscle.

Ovaries

The ovaries are best imaged with ultrasound (either transabdominal or, preferably, transvaginal). Changes in their appearance can be correlated with their functional status. Infantile ovaries are small (except in the neonate when hypertrophy and follicles stimulated by maternal hormones may be a surprising finding) and they enlarge before puberty. Follicular development begins before menstruation, but these cycles and those at the menopause are often imperfect so that follicles may persist and continue enlarging for several months. Normally, ovulation occurs at a follicle size of 20–25 mm diameter and the echo-free follicle is replaced by a corpus luteum which can be cystic or solid. Corpora lutea produce a confusing variety of appearances, whose only consistent feature is their transience (Figure 5.8A–C). In doubtful cases, a rescan at 6 weeks to image them at a different phase of the cycle may be needed to resolve their identity. The postmenopausal ovary is usually too small to identify with ultrasound.

Figure 5.8 Transvaginal scans of the ovary. (A) An inactive ovary is indicated by the caliper marks. It is surrounded by a small amount of free fluid and contains minute developing follicles. (B) Two views of an ovary containing a 3-cm simple cystic structure which presumably represents an unruptured follicle. (C) An ovary in the luteal phase containing a solid corpus luteum.

On CT and MRI, the normal ovaries are often difficult to define, but may be recognized on short inversion recovery MRI sequences as very-high-signal foci in the adnexae.

Investigation of female infertility

The success of in-vitro fertilization (IVF) has been due, in part, to the correct timing of ovulation and subsequent oocyte recovery that ultrasound can provide. Using transabdominal scanning, ovarian follicles of 3–5 mm diameter can be visualized. They appear as echo-free structures amidst the more echogenic ovarian tissue. Their rate of growth is linear and the mean diameter prior to ovulation is 20 mm (range 18–24 mm). Structures within the follicle, such as the cumulus oophorus, can also be visualized. Following ovulation, internal echoes appear because of bleeding. Free fluid may also be observed in the pouch of Douglas.

Transvaginal sonography has largely replaced the transabdominal approach in infertility practice because of the superior anatomical display and because it allows precisely guided aspiration of follicles and fluid in the pouch of Douglas. More precise measurement of follicles is possible, and the corpus luteum is easily recognized. In the midluteal phase, it appears as an oval structure 30–35 mm long and 20–25 mm wide with a wide variety of sonographic appearances (Baerwald et al 2005). Endometrial reflectivity patterns have been proposed as another way to assess ovulation (Randall et al 1989). Ultrasound can only provide presumptive evidence of ovulation/pregnancy. The collection of secondary oocytes constitutes definitive evidence of ovulation. The appearance of internal echoes before the follicle reaches 18 mm or continuous enlargement to 30–40 mm indicates follicular failure.

Ultrasound is also useful for accurate timing of artificial insemination, while a postcoital test can help to differentiate between inadequate sperm penetration and poor mucus production in the presence of immature follicles. Ultrasound scanning is also employed to monitor patients on clomiphene therapy, and there is good correlation between follicular diameter and plasma oestradiol concentration. Ovarian hyperstimulation syndrome is uncommon if gonadotrophin therapy is monitored by ultrasound in conjunction with measurements of plasma oestradiol levels.

The waveforms of blood flow in vessels supplying the ovaries of women undergoing IVF have been studied using transvaginal power Doppler ultrasound (Palomba et al 2008). The observation of blood flow patterns did not improve any reproductive outcomes and is currently not advocated in IVF programmes.

MRI is valuable in the investigation of infertility where uterine pathology is suspected, and provides a particularly high diagnostic yield in patients with dysmenorrhoea and menorrhagia (deSouza et al 1995). It should be part of the investigation of patients with persistent unexplained infertility awaiting costly procedures such as gamete intrafallopian transfer and IVF. MRI should also be used before myomectomy in order to differentiate between leiomyoma and adenomyoma, as attempts to perform a myomectomy on a localized adenomyoma often result in extensive uterine damage.

Adenomyosis and endometriosis

The diagnosis of adenomyosis is often suggested by symptoms of hypermenorrhoea and dysmenorrhoea, but similar symptoms are also produced by leiomyomas. Hysterosalpingography may show multiple small tracks of contrast extending into the myometrium but is now obsolete. Ultrasound in skilled hands may be useful (Dueholm and Lundorf 2007).

Adenomyosis is best demonstrated on T₂-weighted MRI, with which two patterns (focal and diffuse) can be recognized (Hricak et al 1992, Byun et al 1999). In focal adenomyosis, there is a localized ill-defined mixed-signal-intensity mass (adenomyoma) within the myometrium (Figure 5.9). Diffuse adenomyosis presents with diffuse or irregular thickening of the junctional zone, often with underlying high-signal foci (Figure 5.10). Pathologically, this represents smooth muscle hypertrophy and hyperplasia surrounding a focus of basal endometrium. It is the smooth muscle changes that are easily recognized by MRI rather than the foci of heterotopic glandular epithelium. Values for junctional zone thickness from >5 to >12 mm have been suggested for the diagnosis of adenomyosis. In the authors’ experience, however, the thickening of the junctional zone that is described in adenomyosis (Reinhold et al 1999) is not diagnostic of adenomyosis on its own; it may be seen in hypermenorrhoea where no pathological evidence for adenomyosis has subsequently been shown. In these instances, absolute values for junctional zone widths are unhelpful (Hauth et al 2007), and ratios to the width of the outer myometrium or the cervical stroma may be more meaningful.

Figure 5.9 Focal adenomyoma. T₂-weighted spin-echo (SE 2500/80) midline sagittal section through the uterus, demonstrating a large ill-defined mixed-signal intensity mass characteristic of an adenomyoma (arrows).

Figure 5.10 Diffuse adenomyosis. T₂-weighted spin-echo (SE 2500/80) midline sagittal section through the uterus, showing thickening and irregularity of the low-signal band of the junctional zone (short arrows). Diffuse infiltration of a mixed-signal lesion (long arrow) is seen in the posterior wall.