HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gerdes, C. M. Articles by Reeder, S. B. Search for Related Content PubMed PubMed Citation Articles by Gerdes, C. M. Articles by Reeder, S. B. Social Bookmarking                      What's this? Hotlight (NEW!) What's Hotlight?

IDEAL Imaging of the Musculoskeletal System: Robust Water–Fat Separation for Uniform Fat Suppression, Marrow Evaluation, and Cartilage Imaging

¹ Department of Radiology, University of Wisconsin, Madison, WI.
² Present address: Medford Radiological Group, 842 E Main St., Medford, OR 97504.
³ Departments of Medical Physics, Biomedical Engineering, and Medicine, University of Wisconsin, Madison, WI.

Received January 25, 2007; accepted after revision May 23, 2007.

 
S. B. Reeder is married to an employee of GE Healthcare.

Address correspondence to C. M. Gerdes.

WEB

This is a Web exclusive article.

Abstract

Top Abstract Introduction Conventional Methods of Fat... Clinical Utility Conclusion References

 
OBJECTIVE. The objective of this article is to discuss the acquisition of high-quality MR images of the musculoskeletal system with uniform fat suppression using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL). IDEAL is a three-point water–fat separation method that provides robust fat suppression even in the complex magnetic environments commonly encountered during clinical musculoskeletal imaging.

CONCLUSION. The IDEAL technique provides uniform fat saturation even in complex magnetic environments and simultaneously produces in-phase and opposed-phase images that may be useful for characterization of osseous lesions. The IDEAL water–fat separation method is highly versatile and has been successfully combined with T1-weighted, T2-weighted, steady-state free precession, and spoiled gradient-recalled echo techniques to produce high-quality MR images in clinically acceptable scanning times.

Keywords: cartilage imaging • fat-saturation technique • IDEAL imaging • inversion time • marrow imaging • MRI • musculoskeletal imaging • STIR technique

Introduction

Top Abstract Introduction Conventional Methods of Fat... Clinical Utility Conclusion References

 
Several components are required to produce high-quality MR images. Factors significantly affecting image quality include patient motion, signal-to-noise ratio (SNR), image resolution, and tissue contrast. In addition, fat saturation is commonly used in clinical imaging to improve tissue contrast and lesion characterization. Fat appears bright on many pulse sequences, which can obscure underlying abnormalities such as neoplasm and inflammation. Acquisition of high-quality MR images of the musculoskeletal system with uniform fat suppression is particularly challenging because of the complex magnetic environments commonly encountered during clinical musculoskeletal imaging.

Conventional Methods of Fat Suppression

Top Abstract Introduction Conventional Methods of Fat... Clinical Utility Conclusion References

 
How Does It Work?
The most commonly used methods of fat suppression in clinical MRI are chemically selective fat saturation and the STIR method. Frequency-selective fat saturation takes advantage of the difference in resonant frequency that exists between water and fat, approximately –210 Hz at 1.5 T. Based on this "chemical shift," a selective radiofrequency saturation pulse and dephasing gradient can be applied to suppress the lipid signal without significantly affecting the signal coming from nonlipid tissues (water). Alternatively, the STIR technique relies on differences in the T1 relaxation that lead to differences in the longitudinal magnetization between fat and water protons [1]. Based on this difference, an inversion time (TI) can be chosen at precisely the right time to null the signal generated by fat. A nonselective 180° radiofrequency inversion pulse is applied first and is followed by a second 90° pulse. The second pulse is applied at the TI, which is the time the previously inverted longitudinal magnetization of fat crosses the null point. This series of pulses suppresses the signal from the fat protons while preserving the water signal from the tissues within the slice being imaged.

Where These Methods Fail
Despite their widespread use, fat saturation and STIR have several important limitations. Frequency-selective fat saturation is highly sensitive to magnetic field inhomogeneities from susceptibility differences created by the sharp geometric variation of the extremities, off-isocenter imaging, large fields of view, and the presence of metallic hardware. The failure of chemically selective fat saturation in these situations, particularly in the evaluation for edema on T2-weighted images and for enhancement on contrast-enhanced T1-weighted images, can create diagnostic dilemmas; the radiologist often must "read through" these artifacts and may not be confident in differentiating failed fat saturation from abnormalities.

Postoperative imaging of patients with metallic hardware often suffers from both failed fat saturation and signal loss from inadvertent water suppression. The surgical hardware creates a local static magnetic field inhomogeneity that can shift the resonant frequencies of both fat and water. This inadvertent chemical shift prevents the frequency-specific saturation pulse from targeting its intended tissue (fat), thus resulting in poor or failed local fat saturation. In addition, the frequency of the saturation pulse may overlap with the "shifted" frequency of water, causing unwanted suppression of water signal. Clinicians evaluating postoperative patients with metallic hardware are often limited by the inability to effectively evaluate the postoperative site.

The STIR technique provides more uniform lipid saturation than frequency-selective fat-saturation techniques. However, the STIR method can be used only with T2-weighted or proton density–weighted imaging because of the risk of suppressing short T1 species with a T1 similar to that of fat, preventing its use with contrast-enhanced imaging [1]. Signal from tissues such as mucoid materials, hemorrhage, and proteinaceous fluid may also be unintentionally suppressed. In addition, the overall efficacy of STIR imaging is restricted by its reliance on the inversion pulse and relatively long TIs (180–220 milliseconds). STIR also causes partial saturation of the desired signal, greatly reducing the SNR performance of the method.

IDEAL Water–Fat Separation
Iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) is a three-point water–fat separation method that uses asymmetric echoes and least-squares fitting to achieve the maximum possible SNR performance [2, 3]. Echo shifts are optimized to acquire one image with the phase between water and fat in quadrature (i.e., perpendicular) and one image with phase 120° before and 120° after the quadrature image [2, 3]. The IDEAL method uses an iterative approach to estimate the field map and remove its effects from the water–fat decomposition, and a region-growing algorithm [4] is used to prevent fat–water ambiguities that are common to all chemical shift–based methods and that can result in fat–water "swapping." In addition, once water and fat have been separated, they can be recombined into in-phase (water + fat) and out-of-phase (water – fat) images after correction for chemical shift artifact in the readout direction [5]. The IDEAL method has been successfully combined with fast spin-echo [6], spoiled gradient-recalled echo (SPGR) [7], and balanced steady-state free precession (SSFP) techniques [8] to create high-quality fat-suppressed MR images.

IDEAL water–fat separation can be achieved in clinically acceptable scanning times. Although the IDEAL method requires three times the minimum scanning time as conventional methods, it has the same SNR performance as a scan obtained using three signal averages. Therefore, if using the IDEAL technique to replace a protocol that uses multiple averages (e.g., three averages), the number of averages in the IDEAL protocol can be reduced by three while still achieving the same SNR performance and scanning time.

In practice, the IDEAL technique improves SNR efficiency by virtue of the fact that lengthy spatial–spectral pulses or fat-saturation pulses are not required. For example, the TR of our IDEAL SPGR protocol for imaging the knee is approximately 10.7 milliseconds compared with 15 milliseconds for conventional fat-saturated spoiled gradient-echo imaging, representing an approximate reduction of 30% in the TR. This reduction in TR improves SNR efficiency and also offsets the increased minimum scanning time required for the IDEAL technique.

Clinical Utility

Top Abstract Introduction Conventional Methods of Fat... Clinical Utility Conclusion References

 
Reliable Fat Suppression
IDEAL water–fat separation compensates for the effects of field inhomogeneities, providing uniform fat suppression in the challenging magnetic field environments encountered in clinical musculoskeletal imaging while maintaining high SNR (Figs. 1A, 1B, 2A, 2B, 3A, 3B, 4A, 4B). Robust fat suppression facilitates more accurate and more confident interpretations. The IDEAL technique performs well even in the presence of metallic hardware, thus allowing effective postoperative image evaluation (Fig. 5A, 5B). Both unenhanced and contrast-enhanced evaluations of infectious and inflammatory processes, such as osteomyelitis, synovitis, and sacroiliitis, are easily performed using T1-weighted IDEAL fat–water separation techniques (Figs. 6 and 7).

View larger version (88K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A —41-year-old man with foot pain. Sagittal fat-saturated T2-weighted fast spin-echo image (1.5 T, TR/TE = 2,200/58, field of view = 26 cm, slice = 4 mm, 256 x 224, acquisition time = 2 minutes 52 seconds) of foot shows multiple areas of failed chemical shift selective fat suppression within midfoot (arrow) and forefoot (arrowhead).

View larger version (94K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B —41-year-old man with foot pain. Corresponding sagittal iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) T2-weighted fast spin-echo water image (1.5 T, 2,200/60, field of view = 26 cm, slice = 4 mm, 256 x 224, acquisition time = 4 minutes 24 seconds) shows robust, uniform fat suppression within foot.

View larger version (118K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2A —Asymptomatic 35-year-old man. Coronal fat-saturated T2-weighted fast spin-echo image (1.5 T, TR/TE = 2,200/60, field of view = 22 cm, slice = 3 mm, 256 x 224, acquisition time = 2 minutes 52 seconds) of hand shows failure of chemically selective fat-saturation pulse within first metacarpal (arrow) because of field inhomogeneity created by challenging geometry of hand.

View larger version (106K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2B —Asymptomatic 35-year-old man. Corresponding coronal iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) T2-weighted fast spin-echo water image (1.5 T, 2,200/62, field of view = 22 cm, slice = 3 mm, 256 x 224, acquisition time = 5 minutes 4 seconds) shows uniform fat suppression unaffected by magnetic field inhomogeneity and geometry of hand and fingers.

View larger version (101K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3A —33-year-old woman with hand pain and swelling. Coronal contrast-enhanced fat-saturated T1-weighted spin-echo image (1.5 T, TR/TE = 700/10, field of view = 32 cm, slice = 4 mm, 256 x 192, acquisition time = 2 minutes 40 seconds) of wrist and forearm using large field of view to cover area of interest shows high T1 signal within osseous structures of first digit and overlying soft tissues (arrows), raising concern for cellulitis with associated osteomyelitis.

View larger version (102K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 3B —33-year-old woman with hand pain and swelling. Corresponding coronal contrast-enhanced iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) T1-weighted fast spin-echo image (1.5 T, 500/16, field of view = 32 cm, slice = 4 mm, 256 x 192, acquisition time = 5 minutes 42 seconds) shows no abnormal signal within osseous structures. However, diffuse inflammatory enhancement is seen within soft tissues of hand (arrows), confirming presence of cellulitis.

View larger version (124K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4A —57-year-old HIV-positive man with bilateral hip pain. Coronal STIR image (3 T, TR/TE = 6,250/40, inversion time = 130 milliseconds, field of view = 36 cm, slice = 5 mm, 256 x 192, acquisition time = 4 minutes 42 seconds) of pelvis reveals high-signal edema within both acetabuli (arrows). There is associated linear area of low signal within right acetabulum (arrowhead), which suggests presence of insufficiency fracture.

View larger version (127K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 4B —57-year-old HIV-positive man with bilateral hip pain. Corresponding coronal iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) T2-weighted fast spin-echo water image (3 T, 3,567/82, field of view = 36 cm, slice = 5 mm, 320 x 256, acquisition time = 4 minutes 59 seconds) also shows high-signal edema within both acetabuli (arrows) with associated linear area of low signal within right acetabulum (arrowhead). Improved signal-to-noise ratio and higher resolution of IDEAL image allow better visualization of trabecular detail.

View larger version (96K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5A —37-year-old woman with postoperative knee pain. Sagittal fat-saturated T2-weighted fast spin-echo image (3 T, TR/TE = 5,367/83, field of view = 14 cm, slice = 4 mm, 384 x 224, acquisition time = 3 minutes 19 seconds) of knee shows large areas of failed chemical selective fat suppression in distal femur (arrows) and proximal tibia (arrowheads) due to field inhomogeneity from patient's orthopedic hardware.

View larger version (111K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 5B —37-year-old woman with postoperative knee pain. Corresponding sagittal 3D iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) spoiled gradient-recalled echo image (3 T, 12.1/5.75, field of view = 16 cm, slice = 1.2 mm, 512 x 224, flip angle = 14°, acquisition time = 4 minutes 45 seconds) shows uniform robust fat suppression within knee.

View larger version (137K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 6 —15-year-old girl with knee pain and swelling. Sagittal contrast-enhanced 3D iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) spoiled gradient-recalled echo image (3 T, TR/TE = 10.9/4.6, field of view = 16 cm, slice = 1.2 mm, 512 x 224, flip angle = 14°, acquisition time = 4 minutes 45 seconds) of knee shows thickened and nodular enhancing synovium (arrows), which is consistent with synovitis.

View larger version (72K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 7 —48-year-old man with foot pain and swelling. Sagittal contrast-enhanced iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) T1-weighted fast spin-echo image (1.5 T, TR/TE = 567/16, field of view = 16 cm, slice = 4 mm, 256 x 224, acquisition time = 4 minutes 45 seconds) of foot allows radiologist to be confident abnormal signal within bone (arrows) and adjacent soft tissues (arrowheads) is enhancement due to osteomyelitis and cellulitis and not inhomogeneous fat suppression.

Traditionally, the in-phase–opposed-phase technique has played a prominent role in body imaging, the characterization of adrenal lesions in patients with known malignancy, and the detection of hepatic steatosis. However, studies reported in the literature suggest that this technique may also be useful for differentiating benign from neoplastic processes within bone marrow by detecting small amounts of microscopic fat within benign lesions [9, 10]. In addition to fat-suppressed images, the IDEAL technique provides in-phase (water + fat) and opposed-phase (water – fat) images during each acquisition for "free." For this reason, additional examination time is not required to perform in-phase–opposed-phase imaging (Figs. 8A, 8B and 9A, 9B, 9C, 9D).

View larger version (153K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 8A —Coronal iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) images (3 T, TR/TE = 3,567/82, field of view = 36 cm, slice = 5 mm, 256 x 192) of 48-year-old man with bilateral hip pain. Both images were acquired during single acquisition (4 minutes 59 seconds). In-phase image of pelvis shows geographic intermediate signal within both proximal femurs (arrows).

View larger version (152K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 8B —Coronal iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) images (3 T, TR/TE = 3,567/82, field of view = 36 cm, slice = 5 mm, 256 x 192) of 48-year-old man with bilateral hip pain. Both images were acquired during single acquisition (4 minutes 59 seconds). Opposed-phase image shows signal drop (arrows) in areas corresponding to intermediate signal on in-phase image, which confirms normal red marrow.

View larger version (110K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9A —65-year-old man with osseous metastatic disease of spine. All four sagittal iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) T2-weighted fast spin-echo images (3 T, TR/TE = 3,900/98, field of view = 32 cm, slice = 4 mm, 320 x 224) of lumbar spine were acquired simultaneously during single acquisition (4 minutes 18 seconds). Large arrowhead = T12 vertebral body, arrow = posterior L5 vertebral body, and small arrowhead = entire S1 vertebral body. IDEAL water image shows marrow signal abnormality within anterior T12 vertebral body, posterior L5 vertebral body, and entire S1 vertebral body.

View larger version (111K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9B —65-year-old man with osseous metastatic disease of spine. All four sagittal iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) T2-weighted fast spin-echo images (3 T, TR/TE = 3,900/98, field of view = 32 cm, slice = 4 mm, 320 x 224) of lumbar spine were acquired simultaneously during single acquisition (4 minutes 18 seconds). Large arrowhead = T12 vertebral body, arrow = posterior L5 vertebral body, and small arrowhead = entire S1 vertebral body. Corresponding IDEAL fat image shows absence of fat signal within involved vertebral bodies.

View larger version (115K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9C —65-year-old man with osseous metastatic disease of spine. All four sagittal iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) T2-weighted fast spin-echo images (3 T, TR/TE = 3,900/98, field of view = 32 cm, slice = 4 mm, 320 x 224) of lumbar spine were acquired simultaneously during single acquisition (4 minutes 18 seconds). Large arrowhead = T12 vertebral body, arrow = posterior L5 vertebral body, and small arrowhead = entire S1 vertebral body. Corresponding IDEAL in-phase (C) and IDEAL opposed-phase (D) images show no signal drop in involved vertebral bodies, which indicates presence of metastatic disease.

View larger version (122K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 9D —65-year-old man with osseous metastatic disease of spine. All four sagittal iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) T2-weighted fast spin-echo images (3 T, TR/TE = 3,900/98, field of view = 32 cm, slice = 4 mm, 320 x 224) of lumbar spine were acquired simultaneously during single acquisition (4 minutes 18 seconds). Large arrowhead = T12 vertebral body, arrow = posterior L5 vertebral body, and small arrowhead = entire S1 vertebral body. Corresponding IDEAL in-phase (C) and IDEAL opposed-phase (D) images show no signal drop in involved vertebral bodies, which indicates presence of metastatic disease.

View larger version (102K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 10A —Asymptomatic 29-year-old man. Sagittal 3D iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) spoiled gradient-recalled echo image (3 T, TR/TE = 10.9/5.4, field of view = 16 cm, slice = 1.2 mm, 512 x 224, flip angle = 14°, acquisition time = 4 minutes 45 seconds) of knee shows excellent contrast between high-signal articular cartilage (arrow) and low-signal-intensity synovial fluid (arrowhead).

View larger version (96K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 10B —Asymptomatic 29-year-old man. Corresponding sagittal 3D IDEAL nonspoiled gradient-recalled echo acquisition in steady-state image (3 T, 10.9/5.4, field of view = 16 cm, slice = 1.2 mm, 512 x 224, flip angle = 50°, acquisition time = 4 minutes 45 seconds) of knee shows excellent contrast between intermediate-signal articular cartilage (arrow) and high-signal synovial fluid (arrowhead).

View larger version (127K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 11A —18-year-old man with knee pain. Of incidental note is bipartite patella (arrowhead). Sagittal fat-suppressed T2-weighted fast spin-echo image (3 T, TR/TE = 4,967/81, field of view = 14 cm, slice = 4 mm, 384 x 224, acquisition time = 3 minutes 4 seconds) of knee shows normal articular cartilage on femoral trochlea.

View larger version (149K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 11B —18-year-old man with knee pain. Of incidental note is bipartite patella (arrowhead). Corresponding sagittal 3D iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) spoiled gradient-recalled echo image (3 T, 10.9/5.4, field of view = 16 cm, slice = 1.2 mm, 512 x 224, flip angle = 14°, acquisition time - 4 minutes 45 seconds) shows small superficial partial-thickness cartilage defect on femoral trochlea (arrow).

Top Abstract Introduction Conventional Methods of Fat... Clinical Utility Conclusion References

References

Top Abstract Introduction Conventional Methods of Fat... Clinical Utility Conclusion References

 

1. Bydder GM, Steiner RE, Blumgart LH, Khenia S, Young IR. MR imaging of the liver using short TI inversion recovery sequences. J Comput Assist Tomogr 1985; 9:1084 –1089[Medline]
2. Reeder SB, Pelc NJ, Alley MT, Gold GA. Multi-coil Dixon chemical species separation with an iterative least squares method. Magn Reson Med 2004; 51:34 –45
3. Pineda AR, Reeder SB, Wen Z, Pelc NJ. Cramer-Rao bounds for three-point decomposition of water and fat. Magn Reson Med 2005; 54:625 –635[CrossRef][Medline]
4. Yu H, Reeder SB, Shimakawa A, Brittain JH, Pelc NJ. Field map estimation with a regional growing scheme for iterative three-point water–fat decomposition. Magn Reson Med2005; 54:1032 –1039[CrossRef][Medline]
5. Yu H, Reeder SB, Shimakawa A, Gold GE, Pelc NJ, Brittain JH. Implementation and noise analysis of chemical shift correction for fast spin echo Dixon imaging. (abstr) The International Society of Magnetic Resonance 12th annual meeting book of abstracts. Berkeley, CA: International Society of Magnetic Resonance, May2004 : 2686
6. Reeder SB, Pineda AR, Wen Z, et al. Iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL): application with fast spin-echo imaging. Magn Reson Med 2005; 54:636 –644[CrossRef][Medline]
7. Reeder SB, McKenzie CA, Pineda AR, et al. Water–fat separation with IDEAL gradient-echo imaging. J Magn Reson Imaging 2007; 25:644 –652[CrossRef][Medline]
8. Gold GE, Reeder SB, Yu H, et al. Articular cartilage of the knee: rapid three-dimensional MR imaging at 3.0 T with IDEAL balanced steady-state free precession—initial experience Radiology2006; 240:546 –551[Abstract/Free Full Text]
9. Disler DG, McCauley TR, Ratner LM, Kesack CD, Cooper JA. In-phase and out-of-phase MR imaging of bone marrow: prediction of neoplasia based on the detection of coexistent fat and water. AJR1997; 169:1439 –1447[Abstract/Free Full Text]
10. Zajick DC Jr, Morrison WB, Schweitzer ME, Parellada JA, Carrino JA. Benign and malignant processes: normal values and differentiation with chemical shift MR imaging in vertebral marrow. Radiology 2005;237 : 590–596[Abstract/Free Full Text]
11. Siepmann DB, McGovern JM, Gold GE, Brittain JH, Reeder SB. High resolution 3D cartilage imaging of the knee at 3T in 5 minutes. (abstr) The International Society of Magnetic Resonance 14th annual meeting book of abstracts. Berkeley, CA: International Society of Magnetic Resonance, May 2006:125

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gerdes, C. M. Articles by Reeder, S. B. Search for Related Content PubMed PubMed Citation Articles by Gerdes, C. M. Articles by Reeder, S. B. Social Bookmarking                      What's this? Hotlight (NEW!) What's Hotlight?