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Diagnostic Study - Description & Definition

Background

The principles on which nuclear medicine rely on are fundamentally different from some of the other imaging modalities used in radiology. In nuclear medicine radioactive material is administered to the patient converting them into the radiation source, and the images are obtained using a camera. Therefore, this is different from a CT scan or plain radiograph where an external radiation source is directed towards the patient and the rays that pass through are captured using various detectors. In nuclear medicine, small quantities of radioactive materials are administered to the patient and function as radiotracers. These radiotracers can be bound to different compounds depending on the purpose of the study. The compounds have a unique ability of allowing the radiotracer to be guided to a specific target. Once the radiotracer has accumulated in the area of interest, a camera is then used to capture the emitted radiation.

Another fundamental difference of nuclear medicine is that it focuses more on function, not structure. CT or conventional radiographs provide a picture of the human anatomy. Nuclear medicine delivers information on the functioning of these anatomical structures. The radiotracers and their bound compounds are function dependent. An example would be the HIDA scan that works by using Technetium 99m (the radiotracer work horse in nuclear medicine). This is usually tagged with iminodiacetic acid (the compound) that leads to Tc 99m being taken up by hepatocytes. If the patient’s liver is not functioning adequately, their hepatocytes will not take up the radiotracer. These changes can be seen before anatomical abnormalities can be appreciated on other imaging modalities1.

Injecting radioactive compounds are not risk free. The two major factors to consider are the type of radiotracer, and the dose that is being administered. All these radiotracers want to be stable. Thus, for each radiotracer this means reaching a certain number of protons and neutrons. The way these radiotracers reach the ‘zone of stability’ is by either gaining or losing a neutron or a proton. Depending on the initial number of protons/neutrons each radiotracer has, and by the amount of energy that is available to that isotope it will decay into a more stable compound by emitting radiation which can then be captures and processed to produce an image. 

I-131 is an example of a radiotracer which emits high levels of radiation. Some of its uses include treating hyperthyroidism caused by Graves’ disease, or for ablating residual tumor after surgical excision. The patients that receive I-131 are counselled by radiation safety officers and are given strict instruction upon discharge from the hospital. Some of these instructions include limiting contact with family members, not sharing towels or washcloths, and rinsing the tub and sink upon use. This high level of radiation can also be detected by the police, and these patients are given specific documents upon discharge to explain this high level of radiation.  

Radiotracers use in nuclear medicine have variable physical half-lives ranging from a few seconds (Rubidium-82, 75 seconds) to days (I-125, 60 days). Physical half-life means the amount of time in which the radioactivity level decreases to half of its original value. Fortunately, biological half life is another factor which decreases the time the radiotracer remains in the human body. Biological half-life is the time taken for half of radiotracer to be excreted from the human body. An example is Xenon-133 which is used to perform the ventilation portion of a ventilation perfusion scan to assess for pulmonary embolism. The physical half-life of Xe-131 is 5.3 days, but the biological half life is 30 seconds. This is because the radiotracer is exhaled rapidly reducing the total radiotracer dose in the human body.

Description

Bone scan is an imaging technique used to image the osseous structures. Usually, Technetium 99m is tagged with either methylene diphosphonate (MDP) or with hydroxy diphosphonate (HDP). In this example, MDP and HDP are the compounds used. Alternately, a bone scan can also be obtained using F-18 sodium fluoride PET/CT which demonstrates higher sensitivity and specificity2.

To perform a bone scan, the patient is given an intravenous injection of radioactive material and, after an appropriate time interval, is scanned with a gamma camera, which is sensitive to radiation emitted by the injected material. About half of the radioactive material is localized by bone. Bone scans work on the principle of bone turn over (resorption and then replacement by new bone) which occurs continuously through an individual’s life span3. Focal areas which have increased abnormal bone turn over will be see as ‘hot spots’, standing out in a background of mild bone turn over seen in the rest of the normal skeletal system. Unfortunately, this can be nonspecific as multiple pathologies may show increased bone turn over. Pathologies which rely on decreased bone turn over demonstrate ‘cold spots’, and typically are more difficult to identify. Therefore, it is important to have a narrow differential diagnosis before obtaining a bone scan.

The study can be obtained as a single phase (after a single time interval post injection) or as a multi-phase (at multiple time intervals) study depending on the clinical concern. Some of the clinical indications for obtaining a bone scan are detection of occult fractures, skeletal metastases (sclerotic metastasis), osteomyelitis, joint prosthesis infection or loosening, reflux sympathetic dystrophy, heterotopic ossification and Paget’s disease. For the evaluation of occult fractures, skeletal metastasis, and Paget’s disease, a single-phase bone scan is adequate. Bone scans are considered more sensitive for occult fractures which may go undetected on radiographs, but typically require 1 to 10 days after the fracture before the bone scan will detect increased uptake caused by the fracture healing.  This time interval also varies depending on the patient’s age and bone health. 

Multi-phase bone scans require the patient to be imaged at different time points. The first phase images typically show perfusion to a lesion, second phase images show blood flow to the area, and third phase images best show the extent of bone turnover associated with a lesion. Occasionally, an additional delayed scan may be obtained after 24 hours in patients with vasculopathy. These studies are typically reserved for bone infections and reflux sympathetic dystrophy. 

The radiation dose used for a bone scan is minimal (15-40 mCi), and even lower in pediatric patients (0.25mCi/kg). The amount of radiation is so small that there is no risk to people who the patient comes into contact. There is always the minimal risk of damage to cells or tissue from exposure to any radiation dose. Typically, bone scans are not performed on pregnant woman in order to avoid exposing the developing fetus to radiation. 

Normal Study Findings - Images (For abnormal findings images, click on Diagnoses below)
Normal bone scan showing focal uptake in the left antecubital fossa, the site of the intravenous injection.  Also note the physiological excretion of radiotracer by the kidneys as demonstrated by accumulation of radiotracer in the renal pelvis.
Normal, Blood Flow Phase of a 3 phase bone scan with symmetric blood flow to the bilateral hands
Hand and Wrist Bone Scan - Dorsal View; Normal, Blood Pool Phase of a 3 phase bone scan with no focal uptake within the osseous structure to suggest pathology
Hand and Wrist Bone Scan - Palmar View; Normal, Blood Pool Phase of a 3 phase bone scan with no focal uptake within the osseous structure to suggest pathology
Normal, 3 phase bone scan with no focal uptake within the osseous structure to suggest pathology
Normal Study Findings - Video
Diagnoses Where These Studies May Be Used In Work-Up (with abnormal findings images)
Comments and Pearls
  • All types of fractures can be seen on a bone scan, and is considered a more sensitive study compared to a radiograph, but its utility for fractures is limited to special situations.  
  • Scintigraphy if negative, can exclude avascular necrosis, including Keinböck’s disease; however, if positive, it is considered non-specific. It is still considered less sensitive than MRI, which is the preferred imaging technique for these disorders.4,5
  • Two-dimensional images are generally sufficient, but other techniques such as single photon emission computed tomography (SPECT) may be required to view small lesions (<1 cm). SPECT imaging require obtaining an additional CT. Images obtained from the gamma camera are overlaid onto CT images providing us with better anatomical localization6.  For example, SPECT scans can identify occult fractures of the wrist.
  • Lytic lesions are seen are ’cold spots’ (white spots on a background of black bones’) are difficult to appreciate. 
  • Fluorodeoxyglucose (FDG)-PET/CT relies on glucose uptake, and glucose is required for cells which rapidly divide, hence more aggressive tumors rapidly divide and take up more radioactive glucose. FDG-PET/CT is better in assessing lytic lesions, and a bone scan is considered superior in detecting osteoblastic lesions. Overall, FDG-PET/CT is considered more specific than bone scan for metastasis.
  • The more common use of a whole-body bone scan is for the detection of sclerotic osseous metastasis (breast cancer and prostate cancer). 
  • A triple phase bone scan can be used for the detection of osteomyelitis in patients who cannot undergo an MRI. A radiolabeled leukocyte scintigraphy (WBC scan) can also be performed. MRI has superior in evaluating the soft tissues.
  • A triple phase bone scan demonstrates increased uptake on all 3 phases in complex regional pain syndrome.
  • Bone scans can also be used to assess prosthesis loosening.
  • MRI is generally considered more sensitive than a bone scan for the evaluation of acute fractures.
  • MRI is considered as sensitive as a bone scan for the detection of insufficiency fractures, but whole-body bone scans can screen the entire body. MRI provides superior anatomical localization.
  • MRI is more sensitive and specific in evaluating avascular necrosis (Kienbock’s disease) compared to bone scan.
References
  1. Ziessman, H.A. “Hepatobiliary Scintigraphy in 2014”. Journal of Nuclear Medicine Technology, vol. 42, no. 4, Jan. 2014, pp. 249-259., doi:10.2967/jnumed.113.131490.
  2. Wondergem, Maurits et al. “99mTc-HDP bone scintigraphy and 18F-sodiumfluoride PET/CT in primary staging of patients with prostate cancer.” World journal of urology vol. 36,1 (2018): 27-34. doi:10.1007/s00345-017-2096-3
  3. Burch J, Rice S, Yang H, et al. Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high-risk groups. Southampton (UK): NIHR Journals Library; 2014 Feb. (Health Technology Assessment, No. 18.11.) Chapter 1, Background. Available from: https://www.ncbi.nlm.nih.gov/books/NBK261650/
  4. Love C, Din AS, Tomas MB, Kalapparambath TP, Palestro CJ. Radionuclide bone imaging: an illustrative review. Radiographics 2003;23:341-58. PMID 12640151
  5. Lutsky K, Beredjiklian PK. Kienbock disease. J Hand Surg Am 2012;37:1942-52. PMID 22916868
  6. SPECT/CT Imaging: Clinical Utility of an Emerging Technology. Bohdan Bybel, Richard C. Brunken, Frank P. DiFilippo, Donald R. Neumann, Guiyun Wu, and Manuel D. Cerqueira. RadioGraphics 2008 28:4, 1097-1113
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