Detection efficiency of gamma rays through fatty tissue for the external detection of sentinel lymph nodes in breast cancer diagnosis.ABSTRACT. The ability to detect gamma ray gamma ray
Penetrating very short-wavelength electromagnetic radiation, similar to an X-ray but of higher energy, that is emitted spontaneously by some radioactive substances (see gamma decay; radioactivity). passage through fatty tissue has biomedical bi·o·med·i·cal
1. Of or relating to biomedicine.
2. Of, relating to, or involving biological, medical, and physical sciences. applications in the diagnosis of metastatic Metastatic
The term used to describe a secondary cancer, or one that has spread from one area of the body to another.
Mentioned in: Coagulation Disorders
pertaining to or of the nature of a metastasis. breast cancer. The uptake of a [Tc.sup.99m]-labeled sulfur colloid solution colloid solution Fluid therapy A suspension of particles that are so small–1 nm to 1 µm in diameter—that they don't settle out of solution without external force–eg, centrifugation Transfusion medicine into the primary or sentinel lymph nodes Sentinel lymph node
The first lymph node to receive lymph fluid from a tumor. If the sentinel node is cancer-free, then it is likely that the cancerous cells have not metastasized.
Mentioned in: Vulvar Cancer (SLN SLN Sentinel Lymph Node
SLN SUNY (State University of New York) Learning Network
SLN Science Learning Network
SLN Special Local Need
SLN Sri Lanka Navy
SLN Superior Laryngeal Nerve
Sln Slovene (linguistics) ) supplying the breast is one mechanism by which potential metastasis metastasis /me·tas·ta·sis/ (me-tas´tah-sis) pl. metas´tases
1. transfer of disease from one organ or part of the body to another not directly connected with it, due either to transfer of pathogenic microorganisms or to is being assessed. If [gamma]-rays from the decaying [Tc.sup.99m] could be measured externally, the invasiveness of this diagnostic procedure would be greatly reduced. Using a [Co.sup.57] source, this experiment assessed [gamma]-ray intensity attenuation Loss of signal power in a transmission.
The reduction in level of a transmitted quantity as a function of a parameter, usually distance. It is applied mainly to acoustic or electromagnetic waves and is expressed as the ratio of power densities. through porcine porcine /por·cine/ (por´sin) pertaining to swine.
pertaining to pig. See also hog (1), swine.
porcine circovirus 1
a nonpathogenic virus. fatty tissue for thickness up to 76 mm. The porcine tissue accounted for a significant attenuation of intensity, but further significant losses were seen due to the increase in distance between the detector and the [Co.sup.57] source. It was found that porcine fatty tissue has [gamma]-ray attenuation properties nearly identical to that of breast tissue. From the porcine tissue study and subsequent observation of three SLN biopsy procedures, it was found that detecting SLN's via external [gamma]-ray detection is not self-sufficient. The use of a blue dye as an adjunct diagnostic tool is also necessary for the high success rate desired. While an external [gamma]-ray detection method will not replace the traditional SLN biopsy procedure, it may serve as a pre-operative tool to limit the invasiveness of the procedure.
Keywords: Gamma-ray, breast cancer, sentinel lymph node, radiation detection
Breast cancer is the second leading cause of cancer related deaths in the U.S. among women (Ries et al. 2002). Because of breast cancer's high incidence and mortality rate, intense efforts have been made to enable early diagnosis and treatment. Traditionally, diagnostic tools were limited; and treatments such as radical mastectomies were rather extreme. The patient would not only lose the breast, the pectoralis muscles and axillary lymph nodes The Axillary lymph nodes are of large size, vary from twenty to thirty in number, and may be arranged in the following groups:
1. pertaining to lymph or to a lymphatic vessel.
2. a lymphatic vessel.
adj. flow around tumors and to the regional lymph nodes Lymph nodes
Small, bean-shaped masses of tissue scattered along the lymphatic system that act as filters and immune monitors, removing fluids, bacteria, or cancer cells that travel through the lymph system. , but is less invasive than more traditional methods resulting in less trauma to the patient. The determinati on of lymphatic flow from a tumor is done by assessment of the lymph nodes. Each tumor may have from 1-7 primary, or sentinel, lymph nodes that receive circulating lymph from the tumor. Thus immunohistological assessment of the SLN for metastatic tumor cells will determine if metastasis has occurred. A tumor that is supplied by pen-tumor lymph vessels Lymph vessels
Part of the lymphatic system, these vessels connect lymph capillaries with the lymph nodes; they carry lymph, a thin, watery fluid resembling blood plasma and containing white blood cells.
Mentioned in: Birthmarks is more likely to have metastasis occur as the lymphatic system lymphatic system (lĭmfăt`ĭk), network of vessels carrying lymph, or tissue-cleansing fluid, from the tissues into the veins of the circulatory system. is the primary route for metastasis. (Albertini et al. 1996)
The SLN biopsy involves two distinct procedures. The first is an injection of a sulfur-colloid solution radio-labeled with [Tc.sup.99m], a radioisotope radioisotope: see radioactive isotope.
A radioactive isotope used in studying living systems, such as in the investigation of metabolic processes. with a half-life of 6 h which emits 142.7 KeV [gamma]-rays (Firestone 1996). It is important that the gamma rays Gamma rays
Electromagnetic radiation emitted from excited atomic nuclei as an integral part of the process whereby the nucleus rearranges itself into a state of lower excitation (that is, energy content). emitted are low energy as the procedure is diagnostic and the tissue should not be damaged from the radiation exposure. The [Tc.sup.99m]-labeled sulfur colloid solution is injected around the tumor (or peri-nipple if the tumor is near the axillary ax·il·lar·y
Relating to the axilla.
Located in or near the armpit.
Mentioned in: Mastectomy
of or pertaining to the armpit. basin) about 1-6 h prior to the procedure. Some time between the injection and operative procedure a lymphoscintography, which detects gamma rays externally, is performed. The lymphoscintography is done with a gamma camera gamma camera Nuclear medicine A device that evaluates the distribution of a radionuclide in the body post-injection , which indicates to the physician the possible location of radioactive SLN's prior to the operative procedure. If a route for metastasis from the tumor to a primary lymph node lymph node
Small, rounded mass of lymphoid tissue contained in connective tissue. They occur all along lymphatic vessels, with clusters in certain areas (e.g., neck, groin, armpits). exists, [Tc.sup.99m] will collect in the SLN (Noguchi 2002).
In addition to the [Tc.sup.99m] injection, the injection of an isosulfan blue i·so·sul·fan blue
A dye used to mark lymphatic vessels during lymphography. dye circumferentially around the tumor is done just prior to the intra-operative procedure. While the [Tc.sup.99m] method is necessary for accurately identifying the SLN's, it is not sufficient as a diagnostic tool. The use of the blue dye is an alternative means by which SLN(s) may be visually located, leading to increased success rates in diagnosing potential metastasis (Noguchi 2002). The blue dye method acts much like the [Tc.sup.99m], by enabling a visual determination of the lymph vessels and any nodes that supply the tumor region. Cox et al. (1998b) demonstrated the need for both methods in their biopsy of the 844 SLN's they harvested, in which 40.2% were positive for [Tc.sup.99m] only, 32.2% were blue only, and 27.6% were both positive and blue. In another study Cox et al. (1998a) also found results comparable to those above.
The intra-operative procedure employs a gamma detector, several of which are on the market (e.g., the Navigator, US Surgical Corporation, Norwalk, Connecticut, and the Neoprobe, Neoprobe Corp., Dublin, Ohio Dublin is a city in Delaware, Franklin, and Union counties in the U.S. state of Ohio. The population was 31,392 at the 2000 census. In 2006, the population was estimated to be 36,565, and Dublin continues to be one of the fastest-growing suburbs of Columbus. ). The surgeon initially probes externally with the gamma probe confirming potential spots of positive radiation seen on the films from the gamma camera. The surgeon will then incise in·cise
To cut into with a sharp instrument. along the axillary basin accessing potential nodes of interest. In some cases, the surgeon may excise the tumor to remove some of the background noise that can interfere with the sensitivity of the gamma detector. The surgeon will remove any blue staining or radioactive lymph nodes and immunohistological testing will occur to assess for presence of metastasis (Noguchi 2002).
Compared to total axillary lymph node dissection axillary lymph node dissection Surgery The excision of the lymph nodes in the armpit, a procedure commonly performed with mastectomy for breast CA. See Breast cancer. and radical mastectomies, the SLN biopsy has been successful in removing much of the trauma and many of the complications for the patient. There are still some complications, though, that warrant further refinement of the SLN biopsy procedure. The risk for infection, potential for lymphedema, and tissue trauma, as well as the cost due to time and facilities still leaves potential room for improvement (Cox et al. 1998a). Additionally, the SLN biopsy presents no new information for some patients. While a radioactive or blue-dyed SLN is found in most patients, 5-8% will not present with a SLN. Of those patients in which no SLN was found, 1-15% did present with metastasis (Cox et al. 1998a; Cox et al. 1998b; Albertini et al. 1996).
The purpose of this experiment was to investigate the possibility of external detection of [Tc.sup.99m] radioactivity, thus eliminating any unnecessary invasiveness of the procedure. First, the detection of gamma rays through sample tissue (porcine fat) was assessed to ensure that the fatty tissue is analogous to that of human breast tissue. Secondly, the ability to detect gamma rays with both increasing tissue thickness and increasing distance from the [Co.sup.57] source was assessed. The [gamma]-ray intensity was assessed at distances up to 76 mm of tissue.
Two trials were conducted for this experiment. The first trial was done to ensure that the tissue used in the experiment was representative of human breast tissue. The second trial measured not only the attenuation of gamma rays through determined breast tissue thickness (as in trial one), but also took into consideration the change in distance between the source of radiation and the detector, since radiation intensity decreases with increasing distance from the source (Knoll 1989). Both trials were run using a [Co.sup.57] (1 [micro]Curie Curie (kürē`), family of French scientists.
Pierre Curie, 1859–1906, scientist, and his wife,
Marie Sklodowska Curie, 1867–1934, chemist and physicist, b. ) source and a three inch by three inch (76.2 mm by 76.2 mm) NaI detector. [Co.sup.57] was used in this study since its primary [gamma]-ray emission has an energy of 122.1 KeV (Firestone 1996), similar to that of [Tc.sup.99m], 142.7 KeV (Fig. 1), thus giving it similar attenuation properties -- to within 5% -- when passing through matter (ICRU ICRU International Commission on Radiation Units and Measurements
ICRU Iceland’s Crisis Response Unit 1989). The tissue used in each trial was freshly removed from the lumbar region (Anat.) the region of the loin; specifically, a region between the hypochondriac and iliac regions, and outside of the umbilical region.
See also: Lumbar of a pig. The slabs of fat/tissue were sliced into 2-4 mm thick pieces and large enough to cover the entire face of the detector. The [Co.sup.57] source was attached to the bottom of a plastic container, into which increasing layers of fatty tissue were added. For each trial a baseline intensity reading was made through the plastic container, corresponding to zero thickness of tissue. Subsequent intensity readings were taken with increasing thickness of tissue (1-4 mm). Each measurement was taken over a 10 min period during which gamma rays detected were recorded with an Ortec Trump Multi-channel Analyzer (Fig. 2). The [gamma]-ray intensity was determined by integrating counts under the 122.1 KeV [gamma]-ray peak.
Trial 1.--In Trial 1, the gamma ray detector was fixed at 82 mm from the plastic container with the [Co.sup.57] source attached to the bottom of the container. A baseline reading was taken, corresponding to zero tissue thickness, followed by sequential additions of tissue slices with measured thickness. The stack of tissue was periodically measured to ensure that actual thickness present was the sum total of individual slices used.
Trial 2.--In Trial 2, the procedure and set up was the same as Trial 1, except for the positioning of the [gamma]-ray detector. The detector was not fixed, but placed directly upon the tissue, as would be the case in a surgical procedure. As additional thickness of porcine tissue was added, the detector's position relative to the source changed, as it would with increasing thickness of breast tissue during a SLN biopsy procedure.
The attenuation of [gamma]-rays through solid materials is well known through the relation, I = [I.sub.o][e.sup.-e([micro]/e)x], where I is the intensity of [gamma]-radiation passing through a thickness, x, of material. [I.sub.o] is the incident (baseline) radiation of the source (Friedlander 1981). The coefficients [micro] and [rho] are the attenuation coefficients and density of the material studied. For breast tissue, the density is known to have a value of 1.02 g/[cm.sub.3] and [micro]/[rho] is 0.1602 [cm.sub.2]/g (ICRU 1989). Since [rho] and [micro] are known for breast tissue, the expected intensities for increasing thickness could be predicted. Figure 3 shows the data and predicted intensities normalized to a value of 1.0. From the data, it was concluded the porcine tissue used to model breast tissue was representative of the attenuation properties of breast tissue.
The results of Trial 2 are presented in the same fashion as in Trial 1 and are plotted in Fig. 4. The loss of intensity does not exhibit the same behavior as that in Trial 1. The additional loss of intensity observed is due to the change in distance between the Co source and the detector. As expected, the loss of intensity indicates that the greater the separation, the greater the loss of intensity due to geometrical considerations (Knoll 1989). At a distance of 25 mm from the detector, an additional 18% loss in intensity is observed (relative to a fixed detector measurement) and in-creasing intensity losses were recorded for increasing tissue thickness.
It was found that porcine fatty tissue is representative of human breast tissue. At 26 mm breast tissue attenuates 122.1 KeV [gamma]-rays 34.6%, while porcine tissue had a [gamma]-ray intensity attenuation of 33.8%. This has implications in future studies assessing passage of [gamma]-rays through breast tissue, since porcine fatty tissue may substitute for human breast tissue. There are obvious cost and ethical issues that can be avoided with use of porcine tissue versus human tissue.
Secondly, many factors affect the attenuation of [gamma]-ray intensity and efficiency of detection when measuring [gamma]-rays in SLN biopsies. Source half-life, tissue attenuation, geometry, distance, detector efficiency, and infiltration of [Tc.sup.99m] into the lymphatic system all play a significant role in limiting the efficiency of detecting [gamma]-rays.
Since the [Co.sup.57] source used in this study has a half-life of 271 days (Firestone 1996), no appreciable loss of intensity due to decay occurred during the course of the experimentation. In contrast, the TC [99.sup.m] source used in SLN biopsies has a half-life of only 6 h. Therefore a significant loss of intensity will be seen over a several hour period, which could become a significant problem if detection were to occur beyond a certain time period. It is important to note the source strength may differ in different protocols. Radioactive doses ranging from 0.2 mCi to 1.0 mCi have been used in SLN studies (Noguchi 2002).
Geometric factors also play a role in [gamma]-ray intensity measurement. Radioactive sources emit [gamma]-rays isotropically Adv. 1. isotropically - in an isotropic manner and not in a preferential direction. Due to the detector's location on one side of the source and the isotropic Refers to properties that do not differ no matter which direction is measured. For example, an isotropic antenna radiates almost the same power in all directions. In practice, antennas cannot be 100% isotropic. [gamma]-ray emission, there is at least a 50% loss in measurable intensity. Further decreases in intensity are seen as the distance is increased between the source and detector. The detector used in this experiment demonstrated an additional 18% loss in intensity over and above the expected attenuation due to tissue alone at 25 mm from the source. The detector used in this study is relatively large, providing for increased surface area for detection. The actual SLN biopsy procedure utilizes a much smaller probe of 14-19 mm in diameter greatly reducing the number of incident [gamma]-rays that can be detected.
In addition to the loss of intensity due to geometry, there is also a decrease in the recorded intensity of [gamma]-rays due to intrinsic efficiency of the detector. It is known that NaI detectors have a detection efficiency of 10%, as it takes an average of 10 y-rays to produce one recorded event (Friedlander 1981). This detector efficiency provides for a significant loss of detectable events. Further loss is seen by the intercalation intercalation
the insertion of certain organic compounds such as aridines and ethidium bromide that possess a planar aromatic ring structure of appropriate size and geometry so as to insert between base pairs in double-stranded DNA. of the Tc[99.sup.m]-sulfur colloid colloid (kŏl`oid) [Gr.,=gluelike], a mixture in which one substance is divided into minute particles (called colloidal particles) and dispersed throughout a second substance. within the breast tissue and lymphatic system. It has been consistently shown that only 1- 5% of the TC[99.sup.m]-Sulfur colloid actually reaches any given SLN (Cox et al. 1998a; Reintgen et al. 2000). Since only a small amount of radioactivity reaches a SLN, external detection becomes difficult.
To demonstrate the effects of the abovementioned a·bove·men·tioned
The one or ones mentioned previously. factors on the external detection of [gamma]-rays for breast cancer diagnosis, assume a 1 mCi injection of TC[99.sup.m] is administered to the patient. Table 1 illustrates the resulting [gamma]-ray intensity in the detector assuming an operative procedure 6 h following the injection at a detector distance of 25 mm. As evident in Table 1, a small amount of ganuna radiation is detectable during a SLN procedure if detection is attempted externally--illustrating the need for an internal operative procedure to get as close to the SLN's as possible.
Our observations of three SLN procedures (T. Goedde pers. comm.) made evident additional problems for external detection of the gamma radiation gamma radiation, high-energy photons emitted as one of the three types of radiation resulting from natural radioactivity. It is the most energetic form of electromagnetic radiation, with a very short wavelength (high frequency). of interest. As the [Tc-sulfur.sup.99m] colloid intercalates through the breast, a high radioactivity area remains near the injection site. Gamma rays originating from this high-activity area provide for subsequent background noise that is detected as real, recorded [gamma]-rays, but not indicative of SLN's. Since low [gamma]-ray levels are present in a SLN, as demonstrated above, this higher level noise can mask [gamma]-radiation from a SLN of interest. Subsequently, uniquely identifying a SLN in the midst Adv. 1. in the midst - the middle or central part or point; "in the midst of the forest"; "could he walk out in the midst of his piece?"
midmost of background noise becomes difficult when attempted externally.
As has been shown, external [gamma]-ray intensity measurement becomes increasingly difficult due to a variety of factors. Controlling the time-dependent variation in the activity levels is generally accomplished by performing the procedure 2-6 h following the injection; decreasing this interval will allow for increased intensity values. Since much of the detection difficulty is due to proximity of the detector to the source, it is necessary to perform the procedure from an internal versus external perspective to get the detector as close to the source as possible. The operative approach has additional justification as well.
The incorporation of an isosulfan blue dye is done concurrently to assess lymph vessels and SLN's. The fact that not all SLN's demonstrate radioactivity has been shown in multiple studies. Cox et al. (1998a) found that 30% of the 1348 SLN's were found visually with use of the blue dye and not radioactive. In a separate study, Cox et al. (1998b) found 4.6% of 844 SLN's were not radioactive, but presented with blue dye.
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Table 1 Resulting [gamma]-ray intensity in detector due to various detection factors, assuming an initial injection of 1 mCi in patient. Initial dose Detection factor Reduction factor 1 mCi * Tissue attenuation for 25 mm of 0.67 tissue Half-life of [Tc.sup.99m] (6 hours) 0.50 Geometric efficiency 0.50 Detector to source 25 mm 0.82 Infiltration to SLN 0.01 Resulting [gamma]-ray intensity in detector = 0.0014 mCi
This work was supported in part by a Faculty Creative Research Award from the Center for Teaching and Learning Excellence at the University of Southern Indiana The University of Southern Indiana (USI) is a public university in Evansville, Indiana. This publicly-funded institution is rapidly growing and is the fastest growing comprehensive state university in Indiana. .
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Manuscript received 27 March 2002, revised I August 2002.