What parts of the body should be shielded from the useful beam whenever possible?

Employ Shielding whenever Possible

The use of lead shielding can prevent exposure of regions adjacent to the area that is to be imaged from being exposed to any ionizing radiation. Small lead shields can be placed on the table underneath the patient, directly in front of the x-ray beam before it penetrates the patient to protect the gonads or the fetus in the rare instance where fluoroscopy is necessary in a pregnant patient. Although lead shields should be readily available in the fluoroscopy suite, they are seldom practical for use during image-guided injection of the lumbosacral spine because the shield would lie directly in the path of the structures to be imaged.

3.7.4 Uniformity of the X-ray beam

An X-ray tube emits some X-rays in every direction, necessitating lead shielding inside the tube housing to protect the patient and staff from unnecessary exposure. A collimator system is used to adjust the beam to the required size (Box 3.3).

The useful beam is taken off where it is most intense, in a direction perpendicular to the electron stream. The central ray (B in Fig. 3.15) emerges at right angles to the tube axis from the centre of the focal spot. It is usually pointed towards the centre of the area of interest in the body.

Towards the anode edge A of the field, the beam would be cut off by the face of the target. The beam could extend further in the cathode direction but is deliberately cut off at C by the edge of a circular aperture in the lead shield. Thus the X-ray field is made symmetrical around the central ray B, and A and C are the limits of the useful beam.

The maximum size of the useful beam is determined by the angle θ of the anode. In practice, it is narrower than suggested because of the heel effect. As indicated in Figure 3.15, most of the electrons penetrate a few micrometres into the target before being stopped by a nucleus. On their way out, the X-rays are attenuated and filtered by the target material. It will be seen that X-rays travelling towards the anode edge of the field (A) have more target material to cross and so are attenuated more than thosetravelling towards the cathode edge (C). The intensity of the beam decreases across the field, and this is most apparent from B to A. Less importantly, the half-value layer increases because of the filtration effect and, as was noted in section 3.7.1, the effective focal spot decreases. The steeper the target, the greater is the heel effect. At longer FFD, the heel effect is reduced for a given film size.

The heel effect, being gradual, is generally not noticeable even on the largest film. Where the patient's thickness varies considerably across the field, advantage may be taken of the heel effect by positioning the patient with the thicker or denser part towards the cathode of the tube where the exit beam is more intense (see, for example, mammography, Ch. 4.6.3).

The target surface roughens progressively during the life of an X-ray tube because of bombardment by the electrons. As a result, X-rays produced in the ‘valleys’ have to penetrate the ‘hills’ of tungsten, and this both reduces the output of X-rays and increases the heel effect. Overloading of the tube accelerates roughening and its adverse effects.

The intensity of the beam decreases somewhat either side of the central ray, in a direction perpendicular to AC (i.e. parallel to the tube axis), because of the inverse square law, the X-rays at the edges having further to travel.

We have seen that two of the limiting factors in X-ray imaging are the amount of heat that is acceptable to the X-ray tube and the dose of radiation that is acceptable to the patient. A third limiting factor, the sensitivity and performance of the film–screen or other recording media, will be the subject of the following chapters.

Imaging

The most widely used method for imaging is by the scintillation camera (gamma camera). It consists of a lead shielding, a large thin sodium iodide detector, an array of photomultiplier tubes, a collimator with multiple parallel holes and a system for pulse height analysis and for storage and display of the data. By scanning down the body, an image of the distribution of the label is built up and recorded. It can also be used to measure the quantity of the isotope in various organs. By rotating the scintillation camera around the body, single-photon emission computed tomography (SPECT) can be performed to produce sectional images. Positron emission tomography (PET) has augmented scintillation scanning and uses radioisotopes that are positron emitters.7,8

Evaluation

A proposed management algorithm for PABC appears in Fig. 15.10. Early diagnosis has been associated with improved survival rates and relies on the liberal use of imaging strategies and the core and fine-needle biopsy techniques for this group of patients. Mammography in conjunction with abdominal lead shielding can be safely used during pregnancy, but as discussed earlier, the engorged and lactating breast increases tissue density and may mask abnormalities. Ultrasonography yields equivalent information with no known adverse effects to the fetus. Fine-needle aspiration (FNA) may be difficult to interpret cytologically secondary to cellular changes that take place during pregnancy and lactation and is often associated with an increase in the false-negative rate. Core biopsy remains the gold standard in making the diagnosis. When necessary, an open biopsy under local anesthesia is also appropriate. Stopping lactation with ice packs and breast binding or bromocriptine (2.5 mg three times daily for 1 week) beforehand will reduce the risk of a milk fistula. The breasts should be emptied of milk before the biopsy, and a pressure dressing will decrease the risk of hematoma that may develop from the hypervascularity of the pregnant breast.

Approximately 75% to 90% of PABCs are ductal carcinomas, mirroring what is observed in the nonpregnant population. Historically, there was a perceived increase in inflammatory carcinoma of the breast during pregnancy; however, this has since been refuted in contemporary series, in which the incidence ranges from 1.5% to 4.2% among pregnant and nonpregnant patients. Several studies have demonstrated adverse pathologic features in PABC. Most patients with PABC have estrogen receptor (ER)–negative and progesterone receptor (PR)–negative tumors. This may be a result of the production of false-negative results by the ligand-binding assay used for ER and PR when high circulating levels of estrogen and progesterone downregulate receptors. Immunohistochemistry has not been able to detect a difference in the number of hormone receptor–positive tumors when PABC cases are compared with cases of breast cancer in nonpregnant patients of similar ages. Additionally, higher levels of c-ERBB-2 overexpression and p53 mutations have been reported in lactational carcinomas but not in tumors diagnosed during pregnancy. Furthermore, there have been reports of increased HER-2/neu–positive tumors compared with nonpregnant control participant. It is interesting that the HER-2/neu oncogene product p105 is overexpressed not only in ductal carcinomas but also in fetal epithelial cells and the placenta and that toward the end of the third trimester of pregnancy, serum levels of p105 normally rise.

It is known from epidemiologic studies that there is an increased incidence of breast cancers in certain families; the risk increases 5 to 10 times if a patient's mother or sister has had the disease. It is interesting that women with a genetic predisposition to breast cancer may be overrepresented among cases of PABC, with a significant family history of breast cancer being three times more common in women with PABC than among nonpregnant patients with breast cancer. Along these lines, PABC has been associated with a higher rate of BRCA2 allelic mutation compared with sporadic breast cancer. Indeed, a Swedish report of 292 women with breast cancer before the age of 40 years demonstrated a greater likelihood of known BRCA1 and BRCA2 carriers to develop cancer during pregnancy.

Staging of breast cancer currently uses a complicated system jointly recommended by the International Union Against Cancer and the American Joint Committee on Cancer (AJCC) (see Table 14.12). The Haagensen clinical staging for breast cancer is more useful in pointing out the unfavorable prognostic indicators in this disease process. Lateral and posteroanterior chest radiographs in conjunction with lead shielding are considered safe during pregnancy, with an estimated fetal dose of only 0.6 mGy. Provided a catheter is placed to allow rapid drainage of radioactive material from the bladder, a low-dose labeled technetium-99 bone scan is also safe. The low-dose bone scan exposes the fetus to 0.0008 Gy instead of the standard 0.0019 Gy. The higher radiation exposure to the fetus excludes the use of CT in planning a metastatic workup, but MRI may be used to study the thorax and abdomen and to image the skeleton. MRI is preferred to ultrasonography for hepatic imaging and is also the safest and most sensitive way to study the brain.

Gamma and X-Rays

Gamma and x-rays are both electromagnetic radiation but differ in their origin. As stated earlier, gamma rays originate in the nucleus of an atom, while x-rays arise from sources outside the nucleus. Because gamma rays possess more energy that alpha and beta particles, they are able to penetrate much farther into tissue and deposit their energy over larger distances. If lead shielding is used, the density would be much greater, and penetration beyond the lead shield would be much less. If energy emitted is sufficiently low, penetration of the rays is negligible. While lead shielding confers protection, some fraction of energetic gamma-emitters (e.g., 60Cobalt) irradiation can penetrate even lead, and added earth shielding is required. Radiation leakage, which means the penetration of radiation, is usually measured to determine the amount of external radiation that is still present in spite of the presence of a source and shielding. If therapeutic gamma radiation is used instead of x-irradiation, radiation leakage may become as high as 1–10% of the source strength depending on the amount of shielding. Because both gamma rays and x-rays have low LET, travel at a low rate along their path, emerge from the body and continue on their way, x-rays can be used to generate images on a photographic plate.

d Combined Modalities

A combination of irradiation followed by the administration of heterologous platelet anti-sera is used in a well-established rabbit model of severe thrombocytopenia for evaluating platelet replacement therapy.6,31,32, 47–51 Rabbits are exposed to 930 cGy from a 137Cs (cesium) source for 30 minute, with lead shielding of the ears for bleeding time studies. Heterologous platelet a ntiserum from immunized sheep is infused on day 8 after irradiation, producing severe thrombocytopenia (platelet count <10 × 109/L) with 3 to 10% mortality.31

A combination of carboplatin and sublethal irradiation has been used to produce a murine model of life-threatening thrombocytopenic bleeding in which the control group has a 94% mortality and widespread hemorrhage.52 This model was used to evaluate the efficacy of pegylated recombinant thrombopoietin in ameliorating lethal thrombocytopenia.

Brachytherapy sources

1 Dual Detector Probes

The simplest configuration is the dual-detector probe (Hickernell et al., 1988; Daghighian et al., 1994), in which Hickernel and Daghighian use the second detector to provide a measure of the background. The basic configuration is shown in Figure 5. In both cases there was an inner cylindrical detector and an outer annular detector with optical fiber bundles providing the optical coupling to the PMTs.

Hickernel's system was for gamma-ray detection and had lead shielding and collimation. The operating principle was that, if the central detector had a higher count rate than the outer detector, the tumor was in the field of view (FOV).

Daghighian's system was designed to detect positrons and the background was primarily the annihilation radiation produced in other parts of the body. Thus, the outer detector was shielded from the positrons, and its count rate was assumed to be only the annihilation radiation. The system was calibrated with annihilation radiation before use to determine the ratio of the efficiencies of inner and outer detector for the 511-keV radiation. The count rate in the outer detector was multiplied by this ratio and subtracted from the inner detector online to give a net β+ signal.

Evolution of the Niche Concept

In 1868, Ernest Neumann first suggested that blood cells are being replenished throughout postnatal life, and this proposal led to the attempts to localize the place of hematopoiesis. His hypothesis that blood cell production takes place in the bone marrow (BM) was experimentally validated by selective lead shielding of limbs in irradiated animals almost a century later. Notably these and other studies showed that differentiation pathways of immature blood cells are determined by their location and are different between the spleen and the BM. Based on this difference between BM and spleen, Schofield first proposed that there is a specialized place or niche where stem cells reside and are governed. He succinctly posed in 1978 that “stem cell is seen in association with other cells which determine its behavior.”

Trentin further clarified how different sites affected hematopoietic stem/progenitor cell (HSPC) differentiation. Although both spleen and marrow support multiple cell lineages (erythropoietic and granulocytopoietic, for example), the ratios of differentiating cells were distinct: spleen favored erythropoiesis, but BM predominantly supported granulopoiesis. This controlling influence of the surrounding cells was further illustrated by implanting BM stroma into the spleen and showing that hematopoietic cells abruptly changed from erythropoiesis to granulopoiesis at the spleen–BM demarcation. These observations suggest that immature differentiating progenitors require interactions with other specific cell types in a defined microenvironment.

This chapter reviews the current knowledge of the hematopoietic microenvironment during development and in postnatal life in normal hematopoiesis and in myelodysplasia and leukemia. The opportunities for therapeutic manipulation of the niche in the treatment of these disorders are also discussed. For the related topics on stem cell mobilization, hematopoietic cytokines and the role of microenvironment in lymphoid malignancies, plasma cell disorders, and myeloproliferative conditions, readers are referred to other chapters of this book.

Diagnostic Radiation

Diagnostic radiography may be associated with fetal radiation exposure even when studies target maternal anatomy remote from the pregnant uterus (Table 11.1). The fetal consequences of radiation exposure are both dose and time dependent (Table 11.2). However, for most diagnostic procedures, actual fetal exposure is relatively low. The practitioner should limit the amount of radiographic testing if at all possible, but indicated studies should never be withheld because of pregnancy. Lead shielding of the abdomen and pelvis and careful selection of the type of study should be undertaken to minimize the fetal dose. If the amount of fetal exposure is less than 5 rad, there appears to be no significant increased risk of malformations. There is, however, a slightly increased risk of childhood cancer if the fetus is exposed to doses of greater than10 mGy (Doll and Wakeford, 1997). To simplify the various measures of exposure, 1 radiation absorbed dose (rad), 1 Roentgen equivalents man (rem), 10 milliGray (mGy), and 10 milliSievert (mSv) can be considered equivalent (Wang et al., 2012). Iodinated contrast agents have not been shown to be teratogenic. There is a theoretical concern of fetal hypothyroidism, but there have been no reported cases resulting from the use of these agents (Tirada et al., 2015). Use of these agents may also be justifiable with the aim of reducing further radiation exposure from repeated studies.

Magnetic resonance imaging (MRI) has not been shown to have adverse effects on the fetus. However, its safety has yet to be definitively determined. It is generally recommended that MRI be avoided in the first trimester, unless the benefit outweighs the risk (Duchene et al., 1991; Kanal et al., 2007). Gadolinium contrast should be used during pregnancy with extreme caution, given the lack of human safety data and unknown half-life in the fetal compartment (Kanal et al., 2007).