A lecture submitted for2nd term of Oral Radiology Masters

Cairo University Oral & Dental Medicine College

Nuclear Medicine in Oral & Dental Medicine &

Surgey

The use of small amounts of radioactive materials to diagnose

and treat disease.

Nuclear Medicine shows physiology whereas Radiology

shows anatomy.

WHAT IS NUCLEAR MEDICINE?

Nuclear medicine is a branch or specialty of medicine and medical imaging that uses radionuclides and relies on the process of radioactive decay in the diagnosis and treatment of disease.

The principle of nuclear medicine can be simplified into a procedure which detects and produces an image of quantity as well as distribution of radioactivity of the injected isotope in a particular tissue studied.

Definition

Areas where a dental care provider may utilize diagnostic isotopes include head and neck tumors, salivary gland disease, and various metabolic and infectious processes of the head and neck region.

Computed tomography (CT) and magnetic resonance imaging (MRI) with, and without, contrast enhancement can provide high quality static images of the soft and hard tissue under study. However, these imaging modalities provide little physiologic information about a disease process. On the other hand, nuclear medicine scans have the ability to dynamically detect abnormalities at an earlier stage, well before morphological changes are evident.

Physiology before anatomy

The diagnostic modalities of nuclear medicine in oral and dental practice should be increasingly considered and an increased awareness in dental surgeons is needed.

Its application in diagnostic as well as therapeutic fields of oral/maxillofacial pathologies needs discussion and emphasis.

Awareness in Dental fields

Alpha particles (α):

Beta particles (β-):Positrons (β+):Gamma rays: X-rays:

Types of Ionizing Radiation

1) Labeled molecules and compounds, which behave virtually identically to the unlabelled ones in the various chemical, biochemical and biological processes .

2) Radioactive isotopes form compounds in the same way like as the stable isotopes .

3) Isotopes disclose their presence by their radiation, and thus their movement and fate can be traced.

4) For these purposes are used radionuclides that emit electromagnetic waves (g rays) but don’t emit any particle (a, b or neutron).

“Principle & methods”

1-Radionuclides or Radioisotopes2- Gamma camera

Principles of Nuclear Medical Imaging and Image Analysis

Most medical radionuclides are artificially prepared, They are produced by 3 methods:

a-Bombardment of stable element with charged beam (That convert stable nucleus into unstable (radioactive one).

b- Irradiation of stable element with neutrons in a nuclear reactor.

c- Generator production.

Radionuclides production

 Radioisotopes are substances, which contain atomic

nuclei that emit alpha, beta and gamma radiation. If any of these substances are taken into our body they emit radiation when they decay giving us a method of locating where it is present in our body.

The most often used radio-nuclides are Tc-99m in 'single photon' imaging and F-18 in 'positron' imaging.

The selected radioisotope is attached to a convenient chemical compound that is administered to the body(mostly intravenous). It then makes its way through the system leaving a trail of radiation permitting us to trace its path.

Radioisotopes

Radionuclides or Radioisotopes+chemical compound=labeled Radiopharmaceutical.

 Uptake depends on cellular no. or physiology and not physical changes

  In order to investigate a body organ, a suitable radioactive tracer having a particular affinity for that organ is injected into the blood stream this is up taken by the organ of interest, which is then assessed by imaging with the gamma camera(distribution in the body reflects a particular body function or metabolism)

Some Facts about Radionuclides

Half-life: the time taken for a given activity to reach half its initial value.

If the radionuclide has a long half-life, the patient and others would be subjected to a continuous radiation dose.

A short half life such as the six hour half life of technetium 99m, limits the radiation dose, but can give problems of the time required to transport the radio nuclide from the production site to the hospital.

Half Life

Some Radioisotopes Used in Nuclear Medicine

Technetium-99m have a physical short half-life of six hours, 140keV (kiloelectron volt)gamma energy, and the radionuclide- labeled tracers are used in quantities whose emitted radiation doses are far below the amounts that are toxic to human cells.

Tc-99m decays to Tc-99 by emitting a gamma ray.Technetium 99m: where m means metastable: become stable

by emitting gamma rays .80-200 keV is ideal range for gamma camera since

higher will not be absorbed by crystals(NaI)(Ti)and lower will be absorbed by tissue.

The competitive adsorption of technetium- 99m labeled diphosphonates to pure hydroxyapatiteis forty times greater than to pure organic bone matrix. Thus, its uptake correlates well with the rate of mineralization.

Technetium-99m(Tc-99m)

 “Hot spots ”, where the tracer accumulates in greater amounts than normal, can indicate (a tumor, areas of increased bone metabolism, Infection increases the blood supply).

"Cold" spots have no accumulation of the tracer or very little. These may point to (cysts, abscesses, or blood clots, metabolically inactive bone, lack of osteogenesis, or an absent vascular supply).

 Time needed for procedure to be completed: From several seconds to several days for the radiotracer to travel through your body and accumulate in the organ or area being studied (depending on the type of exam).

Radio istopes appear in body organs in the form of:

Immediately A few hours laterOr even several days after pt received the

radioactive material.Fate of radiotracer

The small amount of radiotracer in the body will lose its radioactivity over time.

It circulates through the bloodstream until they are either incorporated into sites of active bone turnover or are excreted in the urine.

As a result, imaging may be done

It may beSuspended over the examination

table or it may be beneath the table. Or dual-headedSome cameras can rotate around the

body and produce more detailed images (SPECT).

Gamma camera capable of recording dynamic as well as static images of the area of interest in the patient

Gamma camera or anger camera

CollimatorDetector crystals (sodium iodide)Photomultiplier tubePre amplifierAmplifier Pulsed height analyser(PHA)X-Y positioning circuitDisplay or recording deviceDetector head 

It is consists of several components

Involves a computed scintillation camera that records the gamma rays emitted by the patient. The camera has a scintillation crystal that fluoresces at the time of interaction with the gamma rays. This fluorescence is detected by photomultiplier tubes, which transform the flashes of light into electronic signals to produce an image that is displayed on a computer monitor.

Principles of operation (Image Acquisition)

Early detection of lesions(nuclear medicine scans are more sensitive than other techniques)

Visualize the structure and function of an organ, tissue, bone or system of the body. E.g. a-analyze kidney function , b-measure thyroid function to detect an overactive or underactive thyroid

Whole body scanning is possible e.g. assessing diseases of the skeleton and detects tumours when their site is unknown.

Monitors behaviour following treatment especially drug induced changes.

Treatment in some diseases (treating cancer. Tumours are destroyed by shooting gamma rays at tumours)

Nuclear medicine therapies include: Radioactive iodine (I-131) therapy used to treat hyperthyroidism (overactive thyroid gland, for example, Graves' disease) and thyroid cancer .

Advantages of Nuclear Medicine

Not diagnostic (doesn’t specify diseases but give range of diseases).

Generally poor resolution compared with other imaging modalities

Radiation risks due to administered radionuclide Can be invasive, usually requiring an injection

into the blood stream. Relatively high costs associated with radio tracer

production and administrationtime-consuming(imaging may take up to several

hours to perform)

Disadvantages of Nuclear Medicine

Nuclear medicine is not safe for the use of human beings, so therefore should not be used on healthy people.

Also the procedure is not recommended for pregnant women because unborn babies have a greater sensitivity to radiation than children or adults.

So Women should inform their physician if there is any possibility of being pregnant or if they are breastfeeding .

The main reason why radioactive sources are used even though they are dangerous is because the patient is already under risk as they are ill, so using the radioactive substances would not put the patient under any further danger but may find a cure for the illness.

Radioactive substances are emitted in to the body so the safest way is to use a radio nuclide which has a short half life, so it can decay to a safe level in the fastest possible time. 

Safety and risk of Nuclear Medicine

Most of the administered radioactive isotopes is excreted as urine via the kidney and bladder but same is excreted as perspiration and saliva. This means that the patient has radio active substances on their skin and should take extra care when around other people. If accidents like urination and vomiting happen, it must be assumed until proven otherwise, that the contamination is radioactive.

Pt should inform about any medications, vitamins and herbal supplements, allergies ,recent illnesses or other medical conditions.

In addition to conventional gamma scintigraphic imaging, the two major nuclear imaging techniques developed are Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SCECT). Both imaging modalities are now standard in the major nuclear medicine services.

Safety and risk of Nuclear Medicine

The amount of radiation from diagnostic nuclear medicine procedures is kept within a safe limit and follows the "ALARA" (As Low As Reasonably Achievable) principle. The radiation dose from nuclear medicine imaging varies greatly depending on the type of study. The effective radiation dose can be lower than or comparable to the annual background radiation dose. It can also be in the range or higher than the radiation dose from an abdomen/pelvis CT scan.

Radiation dose

Clinical Uses in Dentistry

1

one of the most commonly performed diagnostic procedures.

It uses technetium 99 m methylene disphosphonate, (with a half-life of 6 hours and a total radiation dose of 0.3 rads. )which taken in bony areas of high metabolic osteoblastic activity or vascularity. Normal bone should be symmetrical from midline and demonstrate uniform radioisotope uptake.

It is important to keep in mind a bone scan can detect 10-15% mineral loss, while standard radiographs will only visualize a bony defect after 35-50% mineral loss. Overall the scan has a high sensitivity but low specificity.

1- Bone Scanning - Principle

To diagnose and differentiate osteomyelitis from cellulitis.

Detect primary and metastatic malignant disease.

To assess the vascularity of bone grafts.Contribute to the diagnosis of various

metabolic bone diseases such as fibrous dysplasia, Paget’s disease, osteoarthritis, and rheumatoid arthritis (RA).

1 -Bone Scanning - Indications

A normal bone scan should demonstrate symmetry around the midline with uniform uptake of the radiopharmaceutical. There is usually increased activity at joint margins and vertebral bodies. Uptake is typically visualized in the kidneys and bladder.

Reading the Image (Radiograph)

A three-phase bone scan is often performed to obtain additional diagnostic information, especially when the clinician is trying to distinguish osteomyelitis from cellulitis. The three phases include: The dynamic vascular flow phase, where imaging is performed every 2-

3 seconds for the first 30 seconds. In this phase, each side can be compared and differences in vascularity can be seen.

The blood pool image at five minutes, where the radiopharmaceutical is mostly in the vascular compartment but is starting to appear in bone. This phase demonstrates regional differences in blood flow and vascular permeability.

Two to four hours later, the osseous delayed static image is obtained usually for the entire body demonstrating regional distribution in the skeleton. This phase reflects the metabolic activity of the bone in question. In non-inflammatory conditions, the third phase is usually the only image obtained.

Occasionally, a fourth phase study is performed 24 hours later when there may be improved contrast between normal bone and inflammatory conditions.

A three-phase bone scan

 Static acquisition with a detector in a fixed position relative the patient: examination of thyroid, kidney....

 Standard bone scans involve the acquisition of static images three hours after tracer administration. Delayed static images may be useful in the evaluation of benign conditions, such as condylarhyperplasia. The detector move simultaneously and scan the patient's body from head to foot.(eg bone scan)

Three-phase bone scan comprises a flow assessment, a blood pool image, and delayed static views acquisition, which are frequently performed to evaluate trauma, inflammatory disease, and primary bone tumors.Three hours after radiotracer administration, the bony uptake of technetium-99m labeled diphosphonates is maximal, andsignificant proportion of the unbound tracer will be excreted by the kidneys. Therefore, the final delayed static images are acquired at this time.

Tomographic acquisition: The Positron Emission Single Photon (SPECT): detectors rotate around the patient to obtain in a digital representation of a 3D radioactive distribution of the body: chest, pelvis, skull....

 The dynamic flow study requires rapid sequential images for sixty seconds during the intravenous administration of the radiotracer. This is followed by a blood pool image reflecting tissue hyperemia and is acquired immediately after the flow study( kidney and bone phase’s vascular scans).

Different modalities of scintigraphic acquisition are possible:

Bone scans can also use Single Photon Emission Computed Tomography (SPECT) technology where tomographic images obtained in three planes (axial, coronal, and sagittal) allows a more accurate interpretation and better localization of bone pathology. SPECT images are obtained from different angles and then reconstructed by a computer. SPECT can be used for evaluation of, with sensitivity equal to that of a MRI for bone pathology.

2 -SPECT

 SPECT imaging method is equivalent in scintigraphy to Computed Tomography (CT) in radiology. The injected radioactive tracers emit during their disintegration gamma photons which are detected by an external detector, after passing through the surrounding tissue.

In SPECT, the main radioactive isotopes are technetium-99m, Iodine and Thallium-201

It is accomplished by Using rotating camerait is able to provide true 3D information. This

information is typically presented as cross-sectional slices through the patient and can be freely reformatted or manipulated as required.

Single photon emission computed tomography

N.B SPECT studies acquir rotating delayed static images, generally sixty-four projections over 360º, followed by computer reconstruction to provide three dimensional multiplanar slices in the axial, coronal, and sagittal planes, relative to the patient’s body. (e.g.)temporomandibular joints’ internal derangement could be investigated by means of SPECT images.

Collimator The collimator is an important component in a SPECT machine.it include: Two-dimensional parallel channels were The first collimators used (Figure a). By rotating the

detector & collimator assembly around the patient, two-dimensional projections are obtained, and the distribution of radioactivity may be 3D reconstructed slice by slice. These parallel collimators are used in the vast majority of SPECT systems used in Nuclear Medicine services. The resolution of these systems varied from 10 to 15 mm.

converging channels collimators were developed (Figure b).To increase the sensitivity and resolution of SPECT systems, The first proposed included a series of converging channels to a focal line which is parallel to the rotation axis of the system .This system is therefore equivalent to a scanner used in X-ray fan beam tomography where 3D image is reconstructed slice by slice.

  It is used for imaging small organs such as heart and brain, This allows obtaining magnification of

the object in all directions(cross and longitudinal). This kind of collimators can be used only for small field tests, so for small structures, the size of the detectors has not increased. With these systems, image data registration is completely 3D as well as in cone beam X-ray tomography, and therefore reconstruction is not performed slice by slice.

  Diverging collimator (Figure c) is reserved to large structure imaging. Pin-hole collimator (Figure d) allows obtaining a mirror image with a variable magnification

function of collimator depth and object to collimator distance. This collimator is suitable for small structures imaging such as thyroid and hip.

Different kinds of collimators used with SPECT imaging system (O: object, I: image).

Camera head or heads revolve about the patient, acquiring projection images from evenly spaced angles

May acquire images while moving (continuous acquisition) or may stop at predefined angles to acquire images (“step and shoot” acquisition)

Using too few projections creates radial streak artifacts in the reconstructed transverse images After projection images are acquired, they are usually corrected for axis-of-rotation misalignments

and for non uniformities Following these corrections, transverse image reconstruction is performed using either filtered

back projection ((as in CT) )or iterative methods   SPECT image processing parameters include also the following: 1. Filtering: improve image quality by removing noise and blur 2. Reconstruction: by analytical or iterative methods 3. Motion correction: recommended to reduce motion blur due to object motion 4. Attenuation correction: identifying source of attenuation for image correction 5. Quantification: assessment by image quantification of the affected area 6. Normal database: reference used for calculation of extent and severity of defect 7. Segmentation: process of partitioning a digital image into multiple segments to simplify and/or

change the representation of an image into something that is more meaningful and easier to analyze

 

Image acquisition

Gallium 67 citrate, once given intravenously, accumulates non-specifically in areas of inflammation, infection, and neoplasm having an affinity for rapidly dividing cells, i.e., WBC and tumor cells. Gallium can be used in evaluating abscesses, lymphomas, sarcoidosis, and osteomyelitis.

Because of Gallium’s long half-life (78 hrs), if a technetium bone (half-life of 6 hours) scan is being contemplated, it should be performed first.

No longer a common test. A triple phase bone scan is the diagnostic test of choice for confirming the diagnosis of osteomyelitis. However, the triple phase bone scan, while highly sensitive, is non-specific.

Gallium imaging may increase the specificity of a positive bone scan, especially if osteomyelitis is superimposed on another underlying acute or chronic bone disease.

The Gallium scan is also useful for monitoring the response to treatment, with a reduction in Gallium 67 accumulation a good indicator of a resolving osteomyelitis.

3 -Gallium Scan

The major salivary glands with a functioning parenchyma have the ability to take up technetium 99m pertechnetate in sufficient quantities to be imaged, since the Te99 mimics chloride influx into the acinar cells.

Scintigraphy of these glands is used for functional evaluation and evaluating mass lesions. Scintigraphy involves administering a radioactive tracer with an affinity for the organ or tissue of interest; the distribution of the radioactivity is then recorded with a scintillation camera.

Other uses include detecting aplasia or agenesis of the gland, evaluating obstructive disorders, traumatic lesions, fistulas, or function after surgery.

By itself, this study is rarely diagnostic but is a useful adjunct. Initially, images are obtained five minutes after injection of technetium 99m

pertechnetate. After ten minutes, the gland is stimulated by a sour drink or candy. Repeat images

are then obtained. Mass lesions in a gland usually present as areas of decreased uptake, with the

notable exception of Wharthin’s tumor and oncocytomas which demonstrate increased uptake and decreased washout time.

Patients with Sjogren’s Syndrome may have poor uptake of the radiopharmaceutical and poor response to stimulation.

Acute inflammation of the glands usually demonstrates increased uptake and increased washout, whereas chronic inflammation shows decreased uptake.

4 -Salivary Gland Studies

4

The use of positron emission tomography (PET) metabolic imaging has increased significantly over the last several years. PET imaging has value in cardiovascular, neurological, psychiatric, and oncological diagnosis.

PET is a functional imaging modality that allows the measurement of metabolic reactions within the whole body. 18F-fluorodeoxyglocose (FDG) is the radiopharmaceutical most commonly used in PET scanning. FDG is a glucose analog that is transported into cells and phosphorylated like glucose, but the metabolism stops at this point and the phosphorylated FDG becomes trapped in the cell and starts to accumulate.

Most tumors, with a more rapid growth rate, have an increased rate of glucose use due to an increased rate of glycolysis compared to normal tissue or scar tissue. Consequently, FDG preferentially accumulates in tumor cells and demonstrates an increased uptake especially in poorly differentiated tumors. The accumulated FDG is detectable to the PET camera. To assure adequate uptake of FDG, the patients are required to fast to prevent hyperglycemia which would confound the result.

5 -PET Scan

There are many clinical uses for PET in head and neck cancer. PET can detect nodal neck disease in oral squamous cell carcinoma (OSCCA), often at an earlier stage than CT or MRI which rely on morphological change PET can be used to assess the response of a tumor to treatment, diagnose recurrence, detect residual disease, or detect distant unknown metastases. PET scanning is helpful in evaluating a neck mass or evaluating a neck without palpable adenopathy (staged as a N0 neck) in oral squamous cell carcinoma. PET is especially useful when trying to localize an occult primary tumor. PET has not shown any usefulness in pre-operative evaluation of salivary gland neoplasms.

In OSCCA, there has been a great deal of interest in using PET to evaluate the clinically N0 neck for occult or micrometastasis before any changes are visible on CT or MRI.16 Preliminary studies in this area have been very encouraging. If the sensitivity and specificity of PET in evaluating nodal neck disease in OSCCA is found to be clinically acceptable, then many patients will be spared an elective neck dissection. However, PET can give false positive results. FDG may accumulate in non-neoplastic tissue such as new granulation tissue, areas of inflammation, and early post-op scarring. For example, the OSCCA patient with a recently irradiated neck would likely have a false positive result for two to three months after the conclusion of radiation treatment. False positives can also occur in conditions such as tuberculosis and sarcoidosis.

Overall, while the sensitivity can be lacking, the specificity is high.

5 -PET Scan

5

Lymphoscintigraphy is an exciting technique that is receiving much clinical research attention in the treatment of oral and head/neck malignancy, especially OSCCA. Lymphoscintigraphy is already used routinely in the treatment and staging of breast cancer and malignant melanoma.

Briefly, technetium 99m sulfur-colloid is injected in four to six subcutaneous sites around the neoplastic lesion. The radioactive colloid will be carried away in the lymphatic channels to the first echelon lymph node draining that area, the so-called sentinel node. The sentinel node is felt to be the best predictor of nodal spread of the tumor. The pattern of lymphatic spread and the sentinel node can then be imaged using a gamma camera. One to two hours later, in the operating room, the surgeon using a hand held gamma counter is able to localize the node and remove it.

6 -Lymphoscintigraphy

The sentinel node is evaluated for metastatic disease. If the sentinel node is free of disease, it is presumed the remaining nodes in the regional nodal basin are free of disease. On the other hand, if the sentinel node is positive for disease, then the remaining nodes are removed.

Because of sentinel node mapping, many women with breast cancer have been spared full axillary nodal dissections and the sequella of persistent upper extremity lymphadema. The sentinel node is any node that receives drainage from any given anatomic location. It can be located in the neck, axillae, groin, or elsewhere in the body. It can theoretically be in any of the 6 levels of the neck, if it is the primary first echelon node draining the site of a primary malignancy.

Currently there are numerous clinical research protocols being performed at centers across the country where the accuracy of sentinel node biopsy in the treatment of OSCCA is being evaluated. This again could play an important role in the management of the N0 neck, where the sentinel node is removed and evaluated. If the node is disease free, the patient is spared an elective neck dissection. On the other hand, if the node is positive, the patient goes on to a more formal neck dissection.

6 -Lymphoscintigraphy

6

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References:1- Baur DA, Heston TF, Helman JI.

Nuclear Medicine in Oral and Maxillofacial Diagnosis: A Review for the Practicing Dental Professional. J Contemp Dent Pract 2004 February ;(5)1:094-104.

2- INTRODUCTION TO NUCLEAR MEDICINE. Gill Clarke 2005.

3- ENGG 167. MEDICAL IMAGING. Nov. 6. Nuclear Medicine & SPECT imaging. (a lecture from Internet)

References