View source for Bone scintigraphy

{{Short description|Nuclear medicine imaging technique}}
{{distinguish|Dual-energy X-ray absorptiometry}}

{{Infobox diagnostic |
  Name        = Bone scintigraphy |
  Image       = File:Nl bone scan2.jpg|image_size=150px|
  Caption     = A nuclear medicine whole-body bone scan. The nuclear medicine whole-body bone scan is generally used in evaluations of various bone-related pathology, such as for bone pain, stress fracture, nonmalignant bone lesions, bone infections, or the spread of cancer to the bone. |
  ICD10       = |
  ICD9        = {{ICD9proc|92.14}} |
  MeshID      = |
  MedlinePlus = 003833 |
  OPS301      = {{OPS301|3-705}} |
  OtherCodes  = |
}}
A '''bone scan''' or '''bone scintigraphy''' {{IPAc-en|s|ɪ|n|ˈ|t|ɪ|ɡ|r|ə|f|i}} is a [[nuclear medicine]] imaging technique used to help diagnose and assess different bone diseases. These include [[cancer of the bone]] or [[metastasis]], location of bone [[inflammation]] and [[bone fractures|fractures]] (that may not be visible in traditional [[X-ray image]]s), and bone infection (osteomyelitis).<ref>{{cite book|last1=Bahk|first1=Yong-Whee|title=Combined scintigraphic and radiographic diagnosis of bone and joint diseases|date=2000|publisher=Springer|location=Berlin, Heidelberg|isbn=9783662041062|page=3|edition=2nd}}</ref>

Nuclear medicine provides functional imaging and allows visualisation of [[bone metabolism]] or [[bone remodeling]], which most other imaging techniques (such as X-ray [[computed tomography]], CT) cannot.<ref>{{cite journal|last1=Ćwikła|first1=Jarosław B.|title=New imaging techniques in reumathology: MRI, scintigraphy and PET|journal=Polish Journal of Radiology|date=2013|volume=78|issue=3|pages=48–56|doi=10.12659/PJR.889138|pmc=3789933|pmid=24115960}}</ref><ref>{{cite book|last1=Livieratos|first1=Lefteris|title=Radionuclide and Hybrid Bone Imaging |editor1-last=Fogelman|editor1-first=Ignac|editor2-last=Gnanasegaran|editor2-first=Gopinath|editor3-last=van der Wall|editor3-first=Hans|date=2012|publisher=Springer|location=Berlin|isbn=978-3-642-02399-6|page=345|chapter=Basic Principles of SPECT and PET Imaging|doi=10.1007/978-3-642-02400-9_12}}</ref> Bone [[scintigraphy]] competes with [[positron emission tomography]] (PET) for imaging of abnormal metabolism in bones, but is considerably less expensive.<ref>{{cite journal|last1=O'Sullivan|first1=Gerard J|title=Imaging of bone metastasis: An update|journal=World Journal of Radiology|date=2015|volume=7|issue=8|pages=202–11|doi=10.4329/wjr.v7.i8.202|pmid=26339464|pmc=4553252 |doi-access=free }}</ref> Bone scintigraphy has higher [[Sensitivity and specificity|sensitivity]] but lower specificity than CT or MRI for diagnosis of [[scaphoid fracture]]s following negative [[Projectional radiography|plain radiography]].<ref>{{cite journal|last1=Mallee|first1=WH|last2=Wang|first2=J|last3=Poolman|first3=RW|last4=Kloen|first4=P|last5=Maas|first5=M|last6=de Vet|first6=HC|last7=Doornberg|first7=JN|title=Computed tomography versus magnetic resonance imaging versus bone scintigraphy for clinically suspected scaphoid fractures in patients with negative plain radiographs.|journal=The Cochrane Database of Systematic Reviews|date=5 June 2015|volume=2015 |issue=6|pages=CD010023|doi=10.1002/14651858.CD010023.pub2|pmid=26045406|pmc=6464799|doi-access=free}}</ref>

==History==
[[File:Prostate-mets-102.jpg|thumb|right|Bone scan showing multiple bone [[Metastasis|metastases]] from [[prostate cancer]].]]

Some of the earliest investigations into skeletal metabolism were carried out by [[George de Hevesy]] in the 1930s, using [[Isotopes of phosphorus|phosphorus-32]] and by [[Charles Pecher]] in the 1940s.<ref>{{Cite journal|last=Pecher|first=Charles|date=1941|title=Biological Investigations with Radioactive Calcium and Strontium.|journal=Proceedings of the Society for Experimental Biology and Medicine|language=en|volume=46|issue=1|pages=86–91|doi=10.3181/00379727-46-11899|s2cid=88173163|issn=0037-9727}}</ref><ref>{{cite journal|last1=Carlson|first1=Sten|title=A Glance At The History Of Nuclear Medicine|journal=Acta Oncologica|date=8 July 2009|volume=34|issue=8|pages=1095–1102|doi=10.3109/02841869509127236|pmid=8608034|doi-access=free}}</ref>

In the 1950s and 1960s calcium-45 was investigated, but as a [[beta emitter]] proved difficult to image. Imaging of [[positron]] and [[gamma emitter]]s such as [[fluorine-18]] and [[isotopes of strontium]] with [[rectilinear scanner]]s was more useful.<ref>{{cite journal|last1=Bridges|first1=R. L.|last2=Wiley|first2=C. R.|last3=Christian|first3=J. C.|last4=Strohm|first4=A. P.|title=An Introduction to Na18F Bone Scintigraphy: Basic Principles, Advanced Imaging Concepts, and Case Examples|journal=Journal of Nuclear Medicine Technology|date=11 May 2007|volume=35|issue=2|pages=64–76|doi=10.2967/jnmt.106.032870|pmid=17496010|doi-access=free}}</ref><ref>{{cite journal|last1=Fleming|first1=William H.|last2=McIlraith|first2=James D.|last3=Richard King|first3=Capt. E.|title=Photoscanning of Bone Lesions Utilizing Strontium 85|journal=Radiology|date=October 1961|volume=77|issue=4|pages=635–636|doi=10.1148/77.4.635|pmid=13893538}}</ref> Use of [[technetium-99m]] (<sup>99m</sup>Tc) labelled [[phosphate]]s, [[diphosphonates]] or similar agents, as in the modern technique, was first proposed in 1971.<ref>{{cite journal|last1=Subramanian|first1=G.|last2=McAfee|first2=J. G.|title=A New Complex of 99mTc for Skeletal Imaging|journal=Radiology|date=April 1971|volume=99|issue=1|pages=192–196|doi=10.1148/99.1.192|pmid=5548678}}</ref><ref>{{cite book|last1=Fogelman|first1=I|title=Bone Scanning in Clinical Practice|pages=1–6|date=2013|publisher=Springer|location=London|isbn=978-1-4471-1409-3|chapter=The Bone Scan—Historical Aspects|doi=10.1007/978-1-4471-1407-9_1}}</ref>

==Principle==
The most common [[radiopharmaceutical]] for bone scintigraphy is <sup>99m</sup>Tc with [[methylene diphosphonate]] (MDP).<ref>{{cite book|last1=Biersack|first1=Hans-Jürgen|last2=Freeman|first2=Leonard M.|last3=Zuckier|first3=Lionel S.|last4=Grünwald|first4=Frank|title=Clinical Nuclear Medicine|date=2007|publisher=Springer|location=Berlin|isbn=9783540280255|page=243}}</ref> Other bone radiopharmaceuticals include <sup>99m</sup>Tc with HDP, HMDP and DPD.<ref>{{cite book |last1=Weissman |first1=Barbara N |title=Imaging of Arthritis and Metabolic Bone Disease |date=2009 |publisher=Elsevier Health Sciences |isbn=978-0-323-04177-5 |page=17 |url=https://books.google.com/books?id=N94omKNvnVQC&pg=PA17 |language=en}}</ref><ref name="EANMg">{{cite journal|last1=Van den Wyngaert|first1=T.|last2=Strobel|first2=K.|last3=Kampen|first3=W. U.|last4=Kuwert|first4=T.|last5=van der Bruggen|first5=W.|last6=Mohan|first6=H. K.|last7=Gnanasegaran|first7=G.|last8=Delgado-Bolton|first8=R.|last9=Weber|first9=W. A.|last10=Beheshti|first10=M.|last11=Langsteger|first11=W.|last12=Giammarile|first12=F.|last13=Mottaghy|first13=F. M.|last14=Paycha|first14=F.|title=The EANM practice guidelines for bone scintigraphy|journal=European Journal of Nuclear Medicine and Molecular Imaging|date=4 June 2016|volume=43|issue=9|pages=1723–1738|doi=10.1007/s00259-016-3415-4|pmid=27262701|pmc=4932135|doi-access=free}}</ref> MDP [[adsorb]]s onto the crystalline [[hydroxyapatite]] mineral of bone.<ref>{{cite book|last1=Chopra|first1=A|title=Molecular Imaging and Contrast Agent Database|chapter=<sup>99m</sup>Tc-Methyl diphosphonate|date=24 August 2009|pmid=20641923|publisher=National Center for Biotechnology Information (US)|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK24575/}}</ref> Mineralisation occurs at [[osteoblast]]s, representing sites of bone growth, where MDP (and other diphosphates) "bind to the hydroxyapatite crystals in proportion to local blood flow and [[osteoblast]]ic activity and are therefore markers of bone turnover and bone perfusion".<ref>{{cite journal|last1=Brenner|first1=Arnold I.|last2=Koshy|first2=June|last3=Morey|first3=Jose|last4=Lin|first4=Cheryl|last5=DiPoce|first5=Jason|title=The Bone Scan|journal=Seminars in Nuclear Medicine|date=January 2012|volume=42|issue=1|pages=11–26|doi=10.1053/j.semnuclmed.2011.07.005|pmid=22117809}}</ref><ref>{{cite journal|last1=Wong|first1=K. K.|last2=Piert|first2=M.|title=Dynamic Bone Imaging with 99mTc-Labeled Diphosphonates and 18F-NaF: Mechanisms and Applications|journal=Journal of Nuclear Medicine|date=12 March 2013|volume=54|issue=4|pages=590–599|doi=10.2967/jnumed.112.114298|pmid=23482667|doi-access=free}}</ref>

The more active the [[bone turnover]], the more radioactive material will be seen. Some [[tumor]]s, [[bone fracture|fractures]] and [[infection]]s show up as areas of increased uptake.<ref name="jbjs.org">{{cite journal|last1=Verberne|first1=SJ|last2=Raijmakers|first2=PG|last3=Temmerman|first3=OP|title=The Accuracy of Imaging Techniques in the Assessment of Periprosthetic Hip Infection: A Systematic Review and Meta-Analysis.|journal=The Journal of Bone and Joint Surgery. American Volume|date=5 October 2016|volume=98|issue=19|pages=1638–1645|pmid=27707850|url=http://jbjs.org/content/98/19/1638|ref=3|doi=10.2106/jbjs.15.00898|s2cid=9202184 |access-date=20 November 2016|archive-url=https://web.archive.org/web/20161216111550/http://jbjs.org/content/98/19/1638|archive-date=16 December 2016|url-status=dead|url-access=subscription}}</ref>

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]]. 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&nbsp;[[Becquerel|MBq]] of [[Technetium (99mTc) medronic acid|technetium-99m-MDP]] and then scanned with a [[gamma camera]], which captures planar [[Anatomical terms of location#Anterior and posterior|anterior]] and posterior or [[single photon emission computed tomography]] (SPECT) images.<ref name="SNMg">{{cite report|title=Procedure Guideline for Bone Scintigraphy| last1 = Donohoe | first1 = Kevin J.
| last2 = Brown | first2 = Manuel L.
| last3 = Collier | first3 = B. David
| last4 = Carretta | first4 = Robert F.
| last5 = Henkin | first5 = Robert E.
| last6 = O'Mara | first6 = Robert E.
| last7 = Royal | first7 = Henry D.|url=http://snmmi.files.cms-plus.com/docs/pg_ch34_0403.pdf|publisher=Society of Nuclear Medicine|date=20 June 2003|id=3.0}}</ref><ref name="EANMg" /> In order to view small lesions SPECT imaging technique may be preferred over planar scintigraphy.<ref>{{cite book|last1=Kane|first1=Tom|last2=Kulshrestha|first2=Randeep|last3=Notghi|first3=Alp|last4=Elias|first4=Mark|editor1-last=Wyn Jones|editor1-first=David|editor2-last=Hogg|editor2-first=Peter|editor3-last=Seeram|editor3-first=Euclid|title=Practical SPECT/CT in nuclear medicine|date=2013|publisher=Springer|location=London|isbn=9781447147039|page=197|chapter-url=https://books.google.com/books?id=dVhHAAAAQBAJ&pg=PA197|chapter=Clinical Utility (Applications) of SPECT/CT}}</ref>

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).<ref name="SNMg" /><ref name="EANMg" /><ref name="BNMSg">{{cite web|title=Clinical Guideline for Bone Scintigraphy|url=https://cdn.ymaws.com/www.bnms.org.uk/resource/resmgr/guidelines/bnms_bone_scintigraphy.cf_14.pdf|publisher=BNMS|date=July 2014}}</ref> 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.<ref name="BNMSg"/><ref>{{cite book|last1=Weissman|first1=Barbara N.|title=Imaging of arthritis and metabolic bone disease|url=https://archive.org/details/imagingarthritis00mdba|url-access=limited|date=2009|publisher=Mosby/Elsevier|location=Philadelphia, PA|isbn=9780323041775|page=[https://archive.org/details/imagingarthritis00mdba/page/n23 18]}}</ref> 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.<ref>{{cite journal|last1=Schauwecker|first1=D S|title=The scintigraphic diagnosis of osteomyelitis.|journal=American Journal of Roentgenology|date=January 1992|volume=158|issue=1|pages=9–18|doi=10.2214/ajr.158.1.1727365|pmid=1727365}}</ref>

A typical [[effective dose (radiation)|effective dose]] obtained during a bone scan is 6.3 [[millisieverts]] (mSv).<ref>{{cite journal|last1=Mettler|first1=Fred A.|last2=Huda|first2=Walter|last3=Yoshizumi|first3=Terry T.|last4=Mahesh|first4=Mahadevappa|title=Effective Doses in Radiology and Diagnostic Nuclear Medicine: A Catalog|journal=Radiology|date=July 2008|volume=248|issue=1|pages=254–263|doi=10.1148/radiol.2481071451|pmid=18566177}}</ref>

<gallery>
File:Woldobonescan.JPG|Person undergoing a bone scan on the skull
File:SPECT CT.JPG|A patient undergoing a SPECT bone scan.
</gallery>

==PET bone imaging ==
{{main article|PET for bone imaging}}
Although bone scintigraphy generally refers to gamma camera imaging of <sup>99m</sup>Tc radiopharmaceuticals, imaging with [[positron emission tomography]] (PET) scanners is also possible, using [[fluorine-18]] [[sodium fluoride]] ([<sup>18</sup>F]NaF).

For [[Quantification (science)|quantitative]] measurements, <sup>99m</sup>Tc-MDP has some advantages over [<sup>18</sup>F]NaF. MDP renal clearance is not affected by urine flow rate and simplified data analysis can be employed which assumes [[steady state]] conditions. It has negligible tracer uptake in [[red blood cells]], therefore correction for plasma to whole blood ratios is not required unlike [<sup>18</sup>F]NaF. 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]] due to higher [[molecular weight]] than [<sup>18</sup>F]NaF, leading to lower [[capillary permeability]].<ref>{{Cite journal|last1=Moore|first1=A. E.B.|last2=Blake|first2=G. M.|last3=Fogelman|first3=I.|date=2008-02-20|title=Quantitative Measurements of Bone Remodeling Using 99mTc-Methylene Diphosphonate Bone Scans and Blood Sampling|journal=Journal of Nuclear Medicine|volume=49|issue=3|pages=375–382|doi=10.2967/jnumed.107.048595|pmid=18287266|issn=0161-5505|doi-access=free}}</ref>

There are several advantages of the PET technique, which are common to PET imaging in general, including improved [[spatial resolution]] and more developed [[Attenuation#Electromagnetic|attenuation]] 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).<ref>{{cite journal |last1=Segall |first1=G. |last2=Delbeke |first2=D. |last3=Stabin |first3=M. G. |last4=Even-Sapir |first4=E. |last5=Fair |first5=J. |last6=Sajdak |first6=R. |last7=Smith |first7=G. T. |title=SNM Practice Guideline for Sodium 18F-Fluoride PET/CT Bone Scans 1.0 |journal=Journal of Nuclear Medicine |date=4 November 2010 |volume=51 |issue=11 |pages=1813–1820 |doi=10.2967/jnumed.110.082263|pmid=21051652 |doi-access=free }}</ref><ref>{{cite journal |last1=Beheshti |first1=M. |last2=Mottaghy |first2=F. M. |last3=Payche |first3=F. |last4=Behrendt |first4=F. F. F. |last5=Van den Wyngaert |first5=T. |last6=Fogelman |first6=I. |last7=Strobel |first7=K. |last8=Celli |first8=M. |last9=Fanti |first9=S. |last10=Giammarile |first10=F. |last11=Krause |first11=B. |last12=Langsteger |first12=W. |title=18F-NaF PET/CT: EANM procedure guidelines for bone imaging |journal=European Journal of Nuclear Medicine and Molecular Imaging |date=23 July 2015 |volume=42 |issue=11 |pages=1767–1777 |doi=10.1007/s00259-015-3138-y|pmid=26201825 |doi-access=free}}</ref> [<sup>18</sup>F]NaF PET is hampered by high demand for scanners, and limited tracer availability.<ref>{{cite journal |last1=Langsteger |first1=Werner |last2=Rezaee |first2=Alireza |last3=Pirich |first3=Christian |last4=Beheshti |first4=Mohsen |title=18F-NaF-PET/CT and 99mTc-MDP Bone Scintigraphy in the Detection of Bone Metastases in Prostate Cancer |journal=Seminars in Nuclear Medicine |date=November 2016 |volume=46 |issue=6 |pages=491–501 |doi=10.1053/j.semnuclmed.2016.07.003 |pmid=27825429}}</ref><ref>{{cite journal |last1=Beheshti |first1=Mohsen |title=18F-Sodium Fluoride PET/CT and PET/MR Imaging of Bone and Joint Disorders |journal=PET Clinics |date=October 2018 |volume=13 |issue=4 |pages=477–490 |doi=10.1016/j.cpet.2018.05.004 |pmid=30219183|s2cid=52280057 }}</ref>

==References==
{{Reflist}}

== External links==
*{{cite web |url= http://www.webmd.com/hw/health_guide_atoz/hw200283.asp |title= Bone scans |work= WebMD |access-date= July 9, 2008}}

{{Medical imaging}}
{{Bone, cartilage, and joint procedures}}

[[Category:3D nuclear medical imaging]]
[[Category:2D nuclear medical imaging]]
[[Category:Medical imaging]]
[[Category:Radiology]]
[[Category:Scintigraphy]]