X-ray and Gamma Photon Bone Densitometry in Clinical Diagnosis - A Review*

This content was archived on June 24, 2013.

by Michel A. Périard, Consumer and Clinical Radiation Protection Bureau, Health Canada.

* The article: "X-ray and Gamma Photon Bone Densitometry in Clinical Diagnosis - A Review" appeared in The Canadian Journal of Medical Radiation Technology, Winter 2001, 32(4), pgs. 24-32(English), pgs. 33-42 (French).

Table of Contents

• About the Author
• Abstract
• Introduction
• Summary
• Acknowledgements
• References
• Bibliography

About the author

Michel A. Périard, BAppSc (MedImaging), Dipl. T. (Physics), is Head, X-ray Inspection Unit of the X-ray Division, Consumer and Clinical Radiation Protection Bureau, Health Canada. Former positions held were: Radiation Safety Inspector with the X-ray Section, Health Canada; Physics Technologist, with National Dosimetry Services, Health Canada, where he worked in the research and development of thermoluminescent dosimeters; and, Physics Technologist with Defence Research Establishment Ottawa (DREO), Department of National Defence, in the research and development of radiation detection instruments for use by the Canadian Forces.

Abstract

Since the early 1930s, a number of non-invasive radiological techniques have been developed to determine skeletal integrity and identify patients with osteoporosis. From the earliest qualitative methods, based on conventional radiography, have evolved faster and more reliable methods to quantify bone mass. From the 1960s, the development of quantitative absorptiometric techniques, first using gamma photon sources then using x-rays, contributed much to the understanding of the pathophysiology of osteoporosis and other skeletal disorders. These quantitative modalities have provided clinicians with the ability to detect and measure the degree of osteopenia and render an accurate and timely diagnosis, and to initiate appropriate treatment. Continued progress in the accuracy, precision, and long term stability of the equipment used for bone mass measurements has also provided them with the ability to monitor the effectiveness of preventive therapy, and to predict fracture risk. This paper presents a review of some non-invasive modalities, based on gamma and x-ray photon technology used in clinical diagnosis, and discusses their advantages and limitations.

Introduction

Osteoporosis is a common, crippling bone disease associated with a number of risk factors including aging, menopause, and some concurrent illnesses and related drug therapies¹. The disease is characterized by decreased bone mineral density (BMD), resulting from a disruption in the bone remodelling cycle (osteopenia), with a consequent reduction in bone strength with increasing risk of fracture ^{2, 3}. Fractures occur most commonly in the hip (femoral neck), vertebrae or distal radius, after minor trauma ⁴.

Osteoporosis is a significant health problem with serious medical and socio-economic consequences ^{4, 5}. Age related bone loss begins at age 30-35 for both men and women, accelerating in post-menopausal women and leading to a 40% lifetime fracture risk by age 50 ^{6, 7}. In Canada, 1.4 million people suffer from osteoporosis. The disease occurs in one out of four women and one out of eight men over the age of 50. The overall cost related to treating the disease, including consequent osteoporotic fractures, is estimated to be 1.3 billion dollars annually ⁸.

To achieve early diagnosis, monitor, and/or initiate therapeutic management of the disease, or predict fracture risk, a number of noninvasive methods have been developed to evaluate skeletal BMD ^{9, 6, 10}. These methods vary in accuracy, precision (reproducibility), usefulness regarding early detection of the disease and ability to predict fracture risk, and general availability based on health care resources and the cost effectiveness ^{11, 3, 12}.

Radiographic Film Methods: A number of inexpensive radiologic methods have been developed for the detection of osteoporosis using x-ray film, e.g., conventional radiography, photodensitometry, index grading techniques, and radiogrammetry. Although radiographic methods make use of standardized exposure techniques, image quality remains sensitive to several variables. These include radiographic technique factors, film processing, overlying tissue thickness and patient repositioning, which may adversely affect the accuracy and precision of the results ¹⁰.

Conventional radiography [Figure 1 ¹⁰] is a highly subjective (qualitative) method that is influenced much by the image quality, and by the training and experience of the film reader ¹³. Radiographs are insensitive indicators of bone loss and have proven useful only in detecting advanced bone disease, i.e., after an apparent bone loss of about 30-50%, and usually following a fracture 9. To improve diagnostic accuracy, semi-quantitative and quantitative methods were developed to quantify apparent bone loss. These are discussed below.

Photodensitometry (radiographic absorptiometry), described in 1939, was one of the first quantitative methods to measure peripheral BMD from radiographs ¹⁴.The technique uses a soft tissue (water) phantom, in which the hand is immersed, to compensate for soft tissue thickness variations. A reference step wedge is exposed with the extremity and an optical densitometer is used to evaluate the image 15. Accuracy is reported between 9-10%, and can vary up to 15% for bones with thick tissue cover. Precision is between 5-10% ^{11, 10}. Recent advances, using digital image processing [Figure 2 ¹⁴], have improved the accuracy and precision of photodensitometry 14.

Index grading techniques are semi-quantitative methods used to grade and diagnose osteopenia from radiographs such as vertebral or femoral indices [Figure 3 ¹⁰]. These methods lack the sensitivity required for the early detection of osteoporosis. Also, they do not provide good correlation with true bone density, and inter-observer variation greatly limits their usefulness ^{13, 10}.

Radiogrammetry [Figure 4 ¹⁰] is a quantitative method used to measure the cortical thickness of the appendicular skeleton, usually the mid-point of the second metacarpal of the non-dominant hand. This method also relies on obtaining a quality radiographic image and uses a precision needle-tipped calliper (0.1 mm accuracy), to measure the periosteal and endosteal diameters ¹⁶. While image quality remains sensitive to the variables discussed above, precision errors may be as high as 10% due to difficulties in patient repositioning and the calliper measurement of the endosteal diameter ¹². The effective radiation dose equivalent to the hand is low, < 10 µSv ¹⁷.

Although these radiographic methods are inexpensive, and readily accessible, they are not useful for axial skeleton measurements and lack the precision and sensitivity required for the early detection of osteoporosis ¹³. Also, these techniques are not reliable enough to follow the course of the disease, nor useful to predict fracture risk ¹⁸. Conventional radiography does play an important role in the diagnosis of osteoporosis, often discovering consequent fracture(s). However, its limitations make evident the need for accurate and precise quantitative measurement techniques allowing multiple site assessments at low doses. This type of equipment, with improved ability to predict fracture risk, would be preferred for longitudinal studies ^{18, 19, 12}.

Gamma and X-ray Photon Absorptiometry: Radiographic film methods are now superseded by non-invasive quantitative methods, using gamma or x-ray photon sources, to measure BMD ¹⁹. Individual BMD values are compared with average BMD values of a normal reference population. Osteopenia and osteoporosis are defined by the World Health Organization as BMD values less than 1 and [< 2.5] and [≥ 2.5] standard deviations respectively, below the average age and sex matched value of the reference population ¹⁷.

Single-photon absorptiometry (SPA) has been widely used to measure the appendicular BMD since 1963 20. SPA [Figure 5 ¹²] uses a mono-energetic radionuclide source, typically a ¹²⁵I gamma-ray source (27.4 keV), coupled with a scintillation detector and a scanning mechanism to measure the relative attenuation of a gamma beam through bone and soft tissue ²¹. The extremity, usually the non-dominant forearm or the calcaneus, is immersed in a water bath to compensate for differences in overlying tissue thickness²². It is scanned rectilinearly twice across the longitudinal axis where, (1) the photon transmission is measured through bone and soft tissue, and (2) through soft tissue only ^{10, 23}. The two transmission equations24 for the different scanning locations are described by:

bone and soft tissue:

soft tissue only:

where:

Io = the incident beam intensity,
I = the transmitted beam intensity through bone and soft tissue,
I* = the transmitted beam intensity through soft tissue,
μs/ρs = the mass attenuation coefficient of soft tissue (cm²/g),
μb/ρb = the mass attenuation coefficient of bone mineral (cm²/g),
ms1 = the mass of soft tissue per unit area (g/cm²), scanning bone and soft tissue,
mb = the mass of bone mineral per unit area (g/cm²), scanning bone and soft tissue,
ms2 = the mass of soft tissue per unit area (g/cm²), scanning soft tissue only.

From this relationship, the bone mass per unit area (mb) can be calculated using the equation ²⁴ :

where:

ρs = the density of soft tissue (g/cm³),
ρb = the density of bone mineral (g/cm³), and
µb , µs = the mass attenuation coefficients of bone and soft tissue (cm²/g) respectively

Depending on the technology, the resultant transmission count rate is related to BMD and expressed as area density (g/cm²) or volume density (g/cm³) ²². SPA accuracy is within 4-6%, and a number of equipment refinements such as, narrow beam geometry to reduce scattered radiation and thus improve spatial resolution and allow rectilinear scanning, averaged multiple scan paths 1 mm apart, laser light positioning, and the use of a digital image positioning algorithms, have improved precision to within 1-2% ^{25, 13, 26}. The effective dose equivalent is low, < 1 µSv ¹⁷.

Single x-ray absorptiometry (SXA), has now superseded SPA [Figure 6 ¹⁹], i.e., the mono-energetic radionuclide source has been replaced by an x-ray source and K-absorption edge filtration is used ¹⁹. This modification eliminates radionuclide decay and replacement problems, provides greater photon flux, improves image resolution and equipment precision, and shortens scan time to less than 5 minutes per site ¹⁹. SPA and SXA accuracy is about 4-6%, with overlying tissue fat thickness variation remaining the most compromising factor 21. Although peripheral skeleton BMD assessment is used to predict hip and spine fracture risk, there are concerns regarding the correlation between regional BMD measurements and other areas of the body¹⁰. This is further compounded by the difficulty in accurately re-localizing the scan path (or the region of interest) due to the heterogeneity of bone, and thus limiting capability for longitudinal studies ^{19, 27}. The effective radiation dose equivalent to the area scanned is low, < 1 µSv ^{19, 21}.

Dual-photon absorptiometry (DPA) [Figure 7 ¹²] is based on the simultaneous measurement of the relative absorption of two different photon energies through bone and soft tissue, e.g., 40 and 100 keV photons from a ¹⁵³Gd gamma-ray source ^28M. Using two different photon energies simultaneously allows correction for the effects of fat and soft tissue and thus eliminates the need to (1) maintain a constant tissue thickness, and (2) have two separate scans, as described for SPA ¹⁹. DPA can thus provide a reliable and precise measurement of BMD through direct scanning of the entire skeleton, spine, or hip. Precision of 1%, 2%, and 3% for total body, lumbar spine, and femoral neck assessments respectively, and an accuracy within 4-8% can be obtained ^{29, 30}. Using DPA, the mass of bone mineral per unit area is determined as follows. The equations 10 shown below describe the transmission of two photon energy beams E₁ and E₂ (the lower and higher photon energies respectively) through bone and soft tissue at a location (x, y):

where:

= the transmitted photon energies E₁ and E₂ at (x, y),

= the incident beam intensities for energies E₁ and E₂,

= the mass attenuation coefficients for soft tissue (cm²/g) at energies E₁ and E₂,

= the mass attenuation coefficients for bone mineral (cm²/g) at energies E₁ and E₂,

= the mass of soft tissue per unit area (g/cm²), and

= the mass of bone mineral per unit area (g/cm²).

Solving these two equations simultaneously yields the bone mineral mass per unit area ¹⁰:

Although long term precision of the equipment is within 1-2%, yearly replacement of the gamma source, without extensive quality control management, can cause 2-5% changes, and can adversely affect longitudinal studies ^{23, 13}. The effective dose is low, 3-5 µSv ²¹.

Dual-energy x-ray absorptiometry (DEXA) uses an x-ray tube [Figure 6 ¹⁹] as the photon source ¹⁹. Different techniques are used to separate and optimize two peak energies from the poly-energetic x-ray spectrum. These are (1) rapid high voltage switching from 70 to 140 kVp at 60 cycles per second, or (2) using a constant potential x-ray tube with K-absorption edge filtration to produce 40 and 70 keV photons ^{19, 31}. An x-ray tube allows for a higher photon flux and a narrower (pencil) scanning beam (1.5 mm) than DPA (5-8 mm), thus improving precision (from 2% to 1%), image resolution (from 2 mm to 1 mm), and shortening scan time (from 20 min to 2 min) ^{32, 21}. New fan beam units provide a higher photon flux and have consequent faster scan times with improved spatial resolution 19. DEXA accuracy is reported to be within 5-10%, and both short term and long term precision to be 1-2%, an important feature for longitudinal studies ^{33, 34, 25, 35}. However, to minimize inter-machine variability and changes in machine performance, a number of authors advocate the need for the development of standardized quality control protocols for equipment calibration ^{36, 37}. For spine and hip examinations, the effective radiation dose equivalent is < 1-5 µSv for pencil beam units, and about 3-35 µSv for fan beam units, depending on the manufacturer, scanning site, and the method used ^{38, 31, 39}.

Quantitative Computed Tomography (QCT): Computed tomography (CT) scanners, commonly used to produce thin cross-sectional radiographic images of the body, can also be utilized to quantify BMD at any site of the body, typically the spine and proximal femur ^{11, 10}. Conventional CT scanners with special software, or dedicated peripheral CT units, e.g., mono-energetic gamma CT, are used to measure the true volumetric density of bone in g/cm³. QCT sensitivity can not only detect spinal osteoporosis, but has a superior ability than SPA, DPA, or DEXA to predict risk of vertebral fracture ^{18, 9, 21}. The measurement method uses calibration elements exposed with the patient [Figure 8 ¹²], and is independent of cortical bone or other calcifications surrounding the assessed area ¹⁷. However, the method is expensive relative to those previously described, and accuracy errors can be large, i.e., within 4-5% up to 15-20% using dual or single-energy QCT respectively, because of spinal marrow fat content ^{25, 12}. Due to difficulties in patient positioning, and the CT method used, precision can vary, e.g., <1, 2, and 6%, for peripheral, dual, and single-energy CT respectively ^{11, 21, 25}. The effective dose equivalent can be significantly higher than the quantitative methods previously described, i.e., < 2, 50, and 100 µSv for peripheral, single and dual energy QCT respectively ^{11, 25}.

Summary

This paper describes a number of non-invasive methods that have been developed, since the early 1930s, to measure skeletal integrity in an effort to provide early diagnosis of osteoporosis, initiate and monitor preventative therapy, and to predict fracture risk. A review is presented of some radiological methods used in clinical diagnosis, including the earliest qualitative and semi-quantitative techniques to evaluate bone loss, based on conventional radiographic film. These early methods lacked the accuracy and precision required to measure BMD changes over the long term to monitor patients with osteoporosis. This led to the development of quantitative modalities with a high degree of accuracy and precision, based on gamma photon and x-ray absorptiometry (SPA and DPA, SXA and DEXA respectively), and QCT. Although the latter is the most expensive, it is the most sensitive method to detect spinal osteoporosis and to predict vertebral fracture risk, while SXA and DEXA are more precise for longitudinal studies ^{9, 21}. However, difficulties in patient positioning to re-localize the region of interest remain a serious concern limiting the long term precision of equipment used for BMD assessment ^{19, 11, 21, 25}. The development of quality control protocols is required to correct for inter-machine variability, and long term changes in equipment performance ^{36, 37}.

Acknowledgments

The author thanks Mr. P. Dvorak and Ms. N. Martel of the Consumer and Clinical Radiation Protection Bureau (CCRPB), and Dr. H. Swan of the Charles Sturt University in Australia, for their review, comments and recommendations regarding this article. The assistance of D. Gillis and S.A. Harper of CCRPB with respect to the presentation of the illustrations, and that of the staff of the Health Protection Branch Library Network of Health Canada with respect to literature search and article acquisitions, is greatly appreciated. Discussions with and comments by the author's colleagues are also greatly appreciated.

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