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A bone scan or bone scintigraphy is a
nuclear medicine Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is "radiology done inside out" because it records radiation emit ...
imaging technique of the bone. It can help diagnose a number of bone conditions, including
cancer of the bone A bone tumor is an abnormal growth of tissue in bone, traditionally classified as noncancerous (benign) or cancerous (malignant). Cancerous bone tumors usually originate from a cancer in another part of the body such as from lung, breast, thyr ...
or
metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
, location of bone
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
and fractures (that may not be visible in traditional
X-ray image Radiography is an imaging technique using X-rays, gamma rays, or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical radiography ("diagnostic" and "therapeuti ...
s), and bone infection (osteomyelitis). Nuclear medicine provides functional imaging and allows visualisation of
bone metabolism Bone remodeling (or bone metabolism) is a lifelong process where mature bone tissue is removed from the skeleton (a process called '' bone resorption'') and new bone tissue is formed (a process called ''ossification'' or ''new bone formation''). ...
or
bone remodeling Bone remodeling (or bone metabolism) is a lifelong process where mature bone tissue is removed from the skeleton (a process called '' bone resorption'') and new bone tissue is formed (a process called ''ossification'' or ''new bone formation''). ...
, which most other imaging techniques (such as X-ray
computed tomography A computed tomography scan (CT scan; formerly called computed axial tomography scan or CAT scan) is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers ...
, CT) cannot. Bone scintigraphy competes with
positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...
(PET) for imaging of abnormal metabolism in bones, but is considerably less expensive. Bone scintigraphy has higher
sensitivity Sensitivity may refer to: Science and technology Natural sciences * Sensitivity (physiology), the ability of an organism or organ to respond to external stimuli ** Sensory processing sensitivity in humans * Sensitivity and specificity, statisti ...
but lower specificity than CT or MRI for diagnosis of scaphoid fractures following negative plain radiography.


History

Some of the earliest investigations into skeletal metabolism were carried out by George de Hevesy in the 1930s, using phosphorus-32 and by Charles Pecher in the 1940s. In the 1950s and 1960s calcium-45 was investigated, but as a beta emitter proved difficult to image. Imaging of
positron The positron or antielectron is the antiparticle or the antimatter counterpart of the electron. It has an electric charge of +1 '' e'', a spin of 1/2 (the same as the electron), and the same mass as an electron. When a positron collide ...
and
gamma emitter Radionuclides which emit gamma radiation are valuable in a range of different industrial, scientific and medical technologies. This article lists some common gamma-emitting radionuclides of technological importance, and their properties. Fission ...
s such as
fluorine-18 Fluorine-18 (18F) is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380(6) u and its half-life is 109.771(20) minutes. It decays by positron emission 96% of the time and electron capture 4% of the time ...
and isotopes of strontium with rectilinear scanners was more useful. Use of
technetium-99m Technetium-99m (99mTc) is a metastable nuclear isomer of technetium-99 (itself an isotope of technetium), symbolized as 99mTc, that is used in tens of millions of medical diagnostic procedures annually, making it the most commonly used medical r ...
(99mTc) labelled
phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...
s, diphosphonates or similar agents, as in the modern technique, was first proposed in 1971.


Principle

The most common
radiopharmaceutical Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which is ...
for bone scintigraphy is 99mTc with
methylene diphosphonate Medronic acid ( conjugate base, medronate), also known as methylene diphosphonate, is the smallest bisphosphonate. Its complex with radioactive technetium, 99mTc medronic acid, is used in nuclear medicine to detect bone abnormalities, includ ...
(MDP). Other bone radiopharmaceuticals include 99mTc with HDP, HMDP and DPD. MDP
adsorb Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which a f ...
s onto the crystalline
hydroxyapatite Hydroxyapatite, also called hydroxylapatite (HA), is a naturally occurring mineral form of calcium apatite with the formula Ca5(PO4)3(OH), but it is usually written Ca10(PO4)6(OH)2 to denote that the crystal unit cell comprises two entities ...
mineral of bone. Mineralisation occurs at
osteoblast Osteoblasts (from the Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts functi ...
s, representing sites of bone growth, where MDP (and other diphosphates) "bind to the hydroxyapatite crystals in proportion to local blood flow and
osteoblast Osteoblasts (from the Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts functi ...
ic activity and are therefore markers of bone turnover and bone perfusion". The more active the
bone turnover Bone remodeling (or bone metabolism) is a lifelong process where mature bone tissue is removed from the skeleton (a process called '' bone resorption'') and new bone tissue is formed (a process called ''ossification'' or ''new bone formation''). ...
, the more radioactive material will be seen. Some
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s, fractures and
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable d ...
s show up as areas of increased uptake. Note that the technique depends on the osteoblastic activity during remodelling and repair processes following initial osteolytic activity. This leads to a limitation of the applicability of this imaging technique with diseases not featuring this osteoblastic (reactive) activity, for example with
multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, ane ...
. Scintigraphic images remain falsely negative for a long period of time and therefore have only limited diagnostic value. In these cases CT or MRI scans are preferred for diagnosis and staging.


Technique

In a typical bone scan technique, the patient is injected (usually into a vein in the arm or hand, occasionally the foot) with up to 740  MBq of technetium-99m-MDP and then scanned with a
gamma camera A gamma camera (γ-camera), also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy. The applications of scintigraphy include early drug development ...
, which captures planar
anterior Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...
and posterior or
single photon emission computed tomography Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that i ...
(SPECT) images. In order to view small lesions SPECT imaging technique may be preferred over planar scintigraphy. In a single phase protocol (skeletal imaging alone), which will primarily highlight osteoblasts, images are usually acquired 2–5 hours after the injection (after four hours 50–60% of the activity will be fixed to bones). A two or three phase protocol utilises additional scans at different points after the injection to obtain additional diagnostic information. A dynamic (i.e. multiple acquired frames) study immediately after the injection captures perfusion information. A second phase "blood pool" image following the perfusion (if carried out in a three phase technique) can help to diagnose inflammatory conditions or problems of blood supply. A typical effective dose obtained during a bone scan is 6.3
millisieverts The sievert (symbol: SvNot be confused with the sverdrup or the svedberg, two non-SI units that sometimes use the same symbol.) is a unit in the International System of Units (SI) intended to represent the stochastic health risk of ionizing ra ...
(mSv). File:Woldobonescan.JPG, Person undergoing a bone scan on the skull File:SPECT CT.JPG, A patient undergoing a SPECT bone scan.


PET bone imaging

Although bone scintigraphy generally refers to gamma camera imaging of 99mTc radiopharmaceuticals, imaging with
positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...
(PET) scanners is also possible, using
fluorine-18 Fluorine-18 (18F) is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380(6) u and its half-life is 109.771(20) minutes. It decays by positron emission 96% of the time and electron capture 4% of the time ...
sodium fluoride ( sup>18FaF). For
quantitative Quantitative may refer to: * Quantitative research, scientific investigation of quantitative properties * Quantitative analysis (disambiguation) * Quantitative verse, a metrical system in poetry * Statistics, also known as quantitative analysis ...
measurements, 99mTc-MDP has some advantages over sup>18FaF. MDP renal clearance is not affected by urine flow rate and simplified data analysis can be employed which assumes
steady state In systems theory, a system or a process is in a steady state if the variables (called state variables) which define the behavior of the system or the process are unchanging in time. In continuous time, this means that for those properties ' ...
conditions. It has negligible tracer uptake in
red blood cells Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
, therefore correction for plasma to whole blood ratios is not required unlike sup>18FaF. However, disadvantages include higher rates of protein binding (from 25% immediately after injection to 70% after 12 hours leading to the measurement of freely available MDP over time), and less
diffusibility Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
due to higher
molecular weight A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
than sup>18FaF, leading to lower capillary permeability. There are several advantages of the PET technique, which are common to PET imaging in general, including improved
spatial resolution In physics and geosciences, the term spatial resolution refers to distance between independent measurements, or the physical dimension that represents a pixel of the image. While in some instruments, like cameras and telescopes, spatial resoluti ...
and more developed
attenuation In physics, attenuation (in some contexts, extinction) is the gradual loss of flux intensity through a medium. For instance, dark glasses attenuate sunlight, lead attenuates X-rays, and water and air attenuate both light and sound at variable ...
correction techniques. Patient experience is improved as imaging can be started much more quickly following radiopharmaceutical injection (30–45 minutes, compared to 2–3 hours for MDP/HDP). sup>18FaF PET is hampered by high demand for scanners, and limited tracer availability.


References


External links

* {{Bone, cartilage, and joint procedures 3D nuclear medical imaging Medical imaging Radiology Scintigraphy