Original Research
Nuclear Medicine and Molecular Imaging
August 2009

Utility of Delayed Whole-Body Bone Scintigraphy After Directed Three-Phase Scintigraphy

Abstract

OBJECTIVE. The purpose of this study was to determine the diagnostic yield and clinical importance of delayed whole-body bone scintigraphy in directed three-phase examinations.
MATERIALS AND METHODS. The records of 400 consecutively registered patients who underwent combined three-phase and delayed whole-body 99mTc–methylene diphosphonate bone scintigraphy for a variety of indications were reviewed. Clinical indications, findings, recommendations, and outcome were assessed.
RESULTS. Three-phase bone scintigraphy was performed on 156 men and boys and 244 women and girls (61%). Fifty-two patients (13%) were 17 years old or younger, and 236 patients (59%) were older than 40 years. The mean increase in study duration due to whole-body imaging was 25 minutes (range, 21–31 minutes). Excluding the three-phase area of interest, the whole-body examination had a normal tracer distribution in 131 examinations (33%), showed solely degenerative changes in 103 (26%), and showed findings unrelated to the area of interest in 166 patients (41%). In no case did the findings outside the area of interest alter the diagnosis or diagnostic certainty in the three-phase study, but those findings did generate 82 recommendations for additional diagnostic investigation. As a direct result of the recommendations, clinicians requested 18 radiographic, two CT, one MRI, and one ultrasound examinations, one additional bone scan, and two referrals to a consultant. Recommendations based on findings outside the three-phase area of interest affected treatment in one case: Temporomandibular joint uptake resulted in a referral for physical therapy.
CONCLUSION. For most indications, delayed whole-body imaging after directed three-phase bone scintigraphy does not improve diagnostic yield, does not alter patient care, and may be an unnecessary use of medical resources.

Introduction

Three-phase 99mTc-labeled bone scintigraphy is widely used for the evaluation of suspected inflammatory osseous conditions and specific clinical scenarios, including osteomyelitis and septic arthritis [15], inflammatory arthritis [69], prosthesis complications [810], diabetic foot [1113], osteoid osteoma [14], complex regional pain syndrome [15, 16], and sports-related injuries [17]. Three-phase bone scanning involves targeted imaging of the area of interest in the angiographic (flow, immediately after injection), soft-tissue (pool, 2–10 minutes after injection), and delayed (2–4 hours after injection) phases. At our institution, the entire skeleton in addition to the area of interest is imaged during the delayed phase. The literature contains little evidence supporting this practice [18], but the findings provide additional information without increasing the radiation dose to the patient. In addition, the billing code and therefore direct financial cost to the patient associated with limited three-phase bone scintigraphy do not change when whole-body imaging is added to the examination. Delayed whole-body imaging may therefore improve overall diagnostic utility without imparting substantial cost to the patient.
Despite the apparent risk- and expense-free benefits, imaging the entire skeleton in the delayed phase consumes additional time, effort, and institutional resources. Bone scintigraphy is well known to be a sensitive but nonspecific examination [1923]. A lesion incidentally detected in an asymptomatic focus (low pretest probability of disease) may be unrelated to the clinical question. In many cases such a lesion prompts further clinical and diagnostic evaluation that consumes temporal and financial resources [24]. In addition, imaging the entire skeleton increases gamma camera time, which can decrease institutional efficiency. Likewise, there is a concomitant increase in interpretation time spent by radiologists. We hypothesize that for most indications, delayed whole-body imaging after directed three-phase bone scintigraphy does not improve diagnostic yield or alter patient care.

Materials and Methods

Before the initiation of this investigation, institutional review board approval was obtained. The study was performed in compliance with HIPAA. Informed consent from patients was not required owing to institutional policy and the retrospective nature of this investigation.

Subjects

In a search of our institutional electronic medical records system and department of radiology records, we identified the cases of 400 consecutively registered patients who underwent combined three-phase and whole-body 99mTc– methylene diphosphonate (99mTc-MDP) bone scintigraphy between October 8, 2007, and July 9, 2008. These examinations included three-phase studies performed at the specific request of a clinical service and studies designated three-phase studies at the behest of the radiologist. We are uncertain how many studies were in each group because although the history associated with each requisition was available in the electronic medical record, the type of examination requested was not. No limited three-phase examinations without whole-body imaging were included in the data set. All clinical indications were included, and no patient undergoing a combined examination was excluded from the study.

Procedure

Three-phase bone scans of adult patients were obtained after IV injection of approximately 926 MBq (25 mCi) of 99mTc-MDP. The dose was adjusted to body weight for pediatric patients. Scintigraphic images of the area of interest were acquired in the angiographic (3 s/frame for 60 seconds), soft-tissue (200–500K count), and delayed (700K count) phases. In cases in which multiple symptomatic foci were present, the patient was asked by the technologist or radiologist to determine the most symptomatic site, and this area was imaged in the angiographic and soft-tissue phases. Wide-field-of-view whole-body images are not obtained during three-phase examinations at our institution because of the greater resolution with a narrower field of view. Seven to nine overlapping spot projections of the whole body were obtained in the delayed phase. Radionuclide was extracted from 99mTc generators (Technelite, Lantheus Medical Imaging), and MDP (Draximage MDP, Draximage) was labeled and characterized according to the manufacturer's recommendations. Images were obtained with dual-head gamma cameras (e.cam or Symbia S, Siemens Healthcare) with low-energy high-resolution dual-head parallel-hole collimators. The images were digitally viewed on PACS monitors.

Estimating Temporal Cost

A technologist recorded the duration of imaging of 15 patients consecutively undergoing combined targeted three-phase and whole-body 99mTc-MDP bone scintigraphy. The start time was defined as the moment of initiation of acquisition of the first delayed scintigraphic image. The end time was defined as the moment of completion of acquisition of the last delayed scintigraphic image. Mean duration of the examination excluding the imaging time of the area of interest was calculated by subtraction of the duration of imaging of the area of interest from the aggregate imaging duration. Duration of the angiographic and soft-tissue phases was excluded because we assumed this time would be the same whether or not whole-body imaging in the delayed phase was performed.

Grading Clinical Requisitions

Using our institutional electronic medical records system and department of radiology records, we categorized the original clinician-written requisition for the three-phase bone scans as follows: one or two foci of interest, more than two nonarthralgic foci, diffuse arthralgia or fibromyalgia, or known bone marrow disorder or cancer. These categories were mutually exclusive, and no examination was assigned to more than one. In cases in which more than one category was applicable, a tiered assignment system was used: one or two foci of interest had the least weight, more than two nonarthralgic foci and diffuse arthralgia or fibromyalgia had intermediate weight, and known bone marrow disorder or cancer had the greatest weight. The category with the most weighting was selected. The electronic medical records of all patients were interrogated for a history of malignant neoplasm. Requisitions indicating a concern about pediatric osteomyelitis also were identified.

Retrospective Report Analysis

Radiology reports generated for the 400 examinations were retrospectively scored by two diagnostic imagers (3 and 23 years' experience). Discordant opinions were resolved by consensus with a third diagnostic imager (19 years' experience). The region of the body imaged during the flow and pool phases was placed into one of the following categories: knee to foot, femur, pelvis or hips, spine, ribs and chest, shoulder and humerus, elbow to hand, or head. Mentions of a positive finding in a region were noted. Findings outside the area of interest (i.e., not imaged in flow or pool phases) that were mentioned in the final report were categorized in the following manner with multiple categories for each scan possible: normal radiotracer distribution, degenerative change, severe degenerative change, and presence of findings unrelated to the clinical indication. Radiologist recommendations for additional evaluation on the basis of findings outside the area of interest were classified as soft or hard. Soft recommendations included words such as “suggest” and “consider,” and hard recommendations contained the word “recommend.” The specifics of these recommendations were recorded, and the chart was retrospectively reviewed for clinical outcome.

Retrospective Outcome Assessment

To determine whether clinical action was taken as a result of the whole-body findings, the electronic medical records were retrospectively reviewed by the same reviewers and with the same consensus approach as in the retrospective report analysis. Only recommendations based on findings unrelated to the indication and located outside the area of interest were pursued. Clinical consultations conducted and imaging studies performed were scored. Alterations in therapy directly due to radiologist recommendations and alterations made on the basis of recommendation-prompted consultations and imaging findings were recorded.

Results

The study sample included 400 patients (156 men and boys, 244 women and girls; mean age, 45 years; range, 1–90 years). Fifty-two of the patients (13%) were 0–17 years old, and 236 (59%) were older than 40 years. The mean increase in examination duration due to use of whole-body imaging was 25 minutes (range, 21–31 minutes).
Table 1 lists the frequency of each category of clinical indications. Most of the requisitions (83%, 334/400) indicated only one or two foci of interest and were categorized as simple. Review of the medical records indicated that 13% (51/400) of the patients had a medical history of malignant neoplasm (Table 2). No pediatric requisitions identified a concern about osteomyelitis or septic arthritis. Tracer distribution was normal in 131 examinations (33%). Mild or moderate degenerative changes were found in 194 of the examinations (49%), severe degenerative changes in seven (2%), solely degenerative changes in 103 (26%), and findings unrelated to the area of interest in 166 examinations (41%). The mean age of the patients with severe degenerative changes was 73 years (range, 61–87 years).
TABLE 1: Clinician-Written Requisitions Categorized According to Clinical Indication
Clinical IndicationNo. of Requisitions
Simple (one or two foci of interest)334
    Complex regional pain syndrome5
    Infection58
    Prosthesis evaluation38
    Pain106
    Occult fracture or stress reaction86
    Evaluation of lesion seen at another study25
    Other4
    Unrecorded12
Complicated66
    Cancer or bone marrow disorder mentioned22
    Diffuse arthralgia or fibromyalgia29
    More than two nonarthralgic foci15
    Concern about pediatric osteomyelitis
0
TABLE 2: Patients With Known History of Malignant Neoplasm at Time of Combined Scintigraphy
NeoplasmNo. of Patients
No history of malignant neoplasm349
Acute lymphocytic leukemia2
Adrenal cortical carcinoma1
Breast adenocarcinoma10
Chondroblastoma1
Chronic lymphocytic leukemia1
Chronic myelogenous leukemia1
Colonic adenocarcinoma1
Endometrial carcinoma2
Esophageal adenocarcinoma1
Head and neck squamous cell carcinoma3
Lymphoma2
Melanoma1
Multiclonal gammopathy of uncertain clinical significance1
Multiple myeloma1
Myeloproliferative disease not otherwise specified1
Non—small cell lung cancer2
Plasmacytoma1
Poorly differentiated adenocarcinoma, unknown primary1
Prostate adenocarcinoma9
Renal cell carcinoma3
Sarcoma1
Small cell lung cancer1
Squamous cell skin carcinoma1
Urothelial carcinoma1
Vaginal adenocarcinoma1
Yolk sac tumor
1
The findings outside the area of interest did not alter diagnosis or diagnostic certainty about the three-phase findings in any case but did generate 82 recommendations for additional evaluation. Thirty-seven soft (9%) and 45 hard (11%) recommendations led to performance of the following (Table 3): 41 radiographic examinations, eight unspecified imaging studies, four CT examinations, 11 MRI examinations, two nuclear medicine examinations, two ultrasound examinations, one laboratory test, and 34 clinical correlations. Some recommendations included multiple courses of action. As a direct result of these recommendations, clinicians requested 18 radiographic, two CT, one MRI, one ultrasound, and one bone scintigraphic follow-up examinations and two referrals to a consultant (Table 3). Recommendations based on findings outside the three-phase area of interest affected treatment in only one case: Temporomandibular joint uptake resulted in a referral for physical therapy.
TABLE 3: Strength of Recommendations for Evaluation of Incidental Lesions and Diagnostic Course Undertaken
Type of Recommendation
Diagnostic CourseHard (n = 45)Soft (n = 37)Total
Recommended   
    Clinical correlation231134
    Radiography192241
    Unspecified imaging study or studies718
    CT314
    MRI6511
    111In-labeled leukocyte study011
    Bone scan follow-up101
    Ultrasound examination112
    Laboratory study101
Undertaken   
    Radiography13518
    CT112
    MRI101
    111In-labeled leukocyte study000
    Bone scan follow-up101
    Ultrasound examination101
    Laboratory study000
    Specialist referral
1
1
2
    Note—Some recommendations included multiple courses of action.
Six radiologists made final reports of the 400 three-phase bone scintigraphic examinations in this study. The ratio of recommendations made to number of examinations interpreted was as follows: radiologist 1, 37/145 (26%); radiologist 2, 16/77 (21%); radiologist 3, 10/56 (18%); radiologist 4, 10/61 (16%); radiologist 5, 5/44 (11%); radiologist 6, 4/17 (24%).

Discussion

Three-phase 99mTc-labeled methylene diphosphonate bone scanning is popular for the evaluation of certain pathologic conditions and clinical scenarios. It is routine practice at our institution to perform a delayed whole-body examination as part of a focused three-phase study. It can be argued that this practice provides free additional information because no additional radiation dose is used to examine the rest of the body. In a 2002 study, Yang et al. [25], using whole-body imaging performed in all three phases, detected 394 abnormalities during the angiographic and soft-tissues phases in 542 patients. They argued that whole-body three-phase imaging has utility in identifying numerous abnormalities that would not otherwise be detected with delayed whole-body imaging. Those investigators, however, did not specify the number of previously unknown abnormalities or the number of cases in which treatment was altered as a result of lesion detection. They did illustrate cases in which the three-phase data were useful in characterizing a lesion, but the findings simply indicate the usefulness of three-phase imaging irrespective of the field of view. In our series, the whole-body data contributed to only one instance of altered management in 400 consecutively evaluated cases. Furthermore, the discovery of 166 clinically irrelevant findings spawned 82 recommendations and an additional 25 expensive studies and referrals. The institutional and patient expense inherent in these evaluations should be considered in the assessment of the diagnostic appropriateness and overall outcome of delayed whole-body scintigraphy.
The mean increase in duration of bone scans due to whole-body imaging was 25 minutes. During the period of the study, this scanning contributed an additional 167 hours of gamma camera time and technologist work. We did not assess the time radiologists spent interpreting whole-body images, correlating the images with previous images, and contacting referring physicians to alert them to the findings because it was difficult to separate this resource utilization from that for a three-phase study alone. If the time lost obtaining the additional images had been recapitalized, it would have been possible to perform approximately 167 additional bone scans during the dates of the study.
After 20% (82/400) of bone scans in this study, a recommendation was proffered for additional evaluation of whole-body findings outside the three-phase area of interest. As a direct result of these recommendations, clinicians requested 23 additional diagnostic studies and made two referrals to consultants. In many cases, clinicians either did not take a course of action or took a course of diagnostic action different from that recommended by the nuclear radiologist. We did not document repeated patient visits to the ordering physician for discussion of the incidental findings because it was difficult to establish whether the scan findings were the primary reason for the visit. In all cases in which recommendations were made, the medical record was reviewed to determine the outcome of the findings in question. Lesion relevance was followed to the last clinical note or imaging study available. In only one case was an alternative or enhanced diagnosis made on the basis of the incidental findings (temporomandibular joint disorder). Likewise, treatment was altered only once, for this same case of temporomandibular joint disorder.
Findings detected outside the three-phase area of interest on the whole-body images did not alter diagnostic certainty or the primary scintigraphic diagnosis in any case. In addition, even though incidental findings outside the area of interest were seen in 41% (166/400) of examinations, none of the 82 recommendations regarding these findings affected morbidity or mortality. These data suggest that routine acquisition of delayed whole-body images after directed three-phase examinations is not indicated and is an unnecessary expenditure of health care resources. Interestingly, even in clinical scenarios in which one might postulate a high pretest probability of the presence of multifocal disease, the delayed whole-body findings were not useful. Thirteen percent (51/400) of patients who underwent imaging in this study had a history of malignant neoplasia; 59% (236/400) of the patients were older than 40 years; and 11% (44/400) of requisitions indicated the presence of multifocal symptoms.
There were several limitations to this study. Although 13% (51/400) of patients had a history of malignant neoplasia, the disease status and tumor burden at the time of the examination were not ascertained. In addition, the list of neoplasms was a heterogeneous set, as indicated in Table 2. Despite these limitations, we suggest that delayed-phase whole-body bone scintigraphy may already be part of the surveillance protocol for neoplasms with a high yield from bone scintigraphy, and obtaining additional images at unscheduled times to evaluate asymptomatic foci may not benefit the treatment of these patients. We cannot comment on the validity of combined whole-body and three-phase examinations for pediatric osteomyelitis because none of the pediatric patients in our study had that indication. This finding was surprising and may indicate either an anomaly in our referral pattern or that other imaging studies (e.g., MRI) are being used in lieu of bone scintigraphy. Pediatric osteomyelitis is well known to be hematogenously disseminated [26], and it is possible that imaging the entire skeleton may be of benefit to these patients. Because our study included only patients from our institution, referral bias may have affected our results. Last, it is possible that although rare, some lesions incidentally detected at whole-body imaging during three-phase examinations may be clinically significant and that missing these lesions can delay diagnosis and increase cost. It may be necessary to increase our sample size to identify these cases and determine what if any savings are imparted by their detection.
Our data are evidence that routine wholebody imaging after directed three-phase diphosphonate bone scintigraphy does not improve diagnostic yield, does not alter patient care, and is an unnecessary use of medical resources. Adding whole-body images may be beneficial in selected individual circumstances, but those circumstances should be the exception and not the rule. In this era of expense reduction and efficiency, radiologists should be mindful of the hidden costs of imaging and make an effort to maximize the yield of the studies they perform.

Footnote

Address correspondence to M. S. Davenport ([email protected]).

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Information & Authors

Information

Published In

American Journal of Roentgenology
Pages: 338 - 342
PubMed: 19620429

History

Submitted: November 19, 2008
Accepted: February 5, 2009

Keywords

  1. bone scintigraphy
  2. cost-effectiveness
  3. incidental findings
  4. radiologist recommendations
  5. three-phase bone scan

Authors

Affiliations

Matthew S. Davenport
All authors: Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr., UH B1-D502, Ann Arbor, MI 48109-5030.
Richard K. J. Brown
All authors: Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr., UH B1-D502, Ann Arbor, MI 48109-5030.
Kirk A. Frey
All authors: Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr., UH B1-D502, Ann Arbor, MI 48109-5030.

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