Imaging Assessment of Imaging Assessment of Diabetic Foot InfectionsDiabetic Foot Infections
Regina Alivisatos, MDRegina Alivisatos, MDMedical Officer Medical Officer
DSPIDPsDSPIDPs
IntroductionIntroduction
Patients with osteomyelitis should be identifiedPatients with osteomyelitis should be identifiedin order to ensurein order to ensure the most appropriate course of treatmentthe most appropriate course of treatment a homogenous clinical trials populationa homogenous clinical trials population
7 – 14% of enrolled subjects found to have7 – 14% of enrolled subjects found to haveosteomyelitisosteomyelitis excluded from the PP populationsexcluded from the PP populations failures in the ITT analysisfailures in the ITT analysis
WHY?WHY?
Decreasing size of the PP populations that may be Decreasing size of the PP populations that may be distributed unequally distributed unequally
Inaccurate assessment of the true efficacy for Inaccurate assessment of the true efficacy for one or both of the treatment armsone or both of the treatment arms
Database size insufficient to draw conclusions about a Database size insufficient to draw conclusions about a drugs efficacy in CSST infections or in the diabetic drugs efficacy in CSST infections or in the diabetic foot subsetfoot subset
Applications to DateApplications to DateDiagnostiDiagnosti
c c ProcedureProcedure
ApplicationsApplications*done at investigator’s discretion*done at investigator’s discretion
AA BB CC DD EE FF GGX/RX/R X*X* X*X* X*X* XX X*X*
Bone ScanBone Scan X*X*In ScanIn Scan X*X*
MRIMRI X*X*ProbeProbe XX
Bone biopsyBone biopsy X*X*UnknownUnknown XX XX
ComplicationsComplications
Determination of infection complicated because of Determination of infection complicated because of superimposed neuropathic osteoarthropathy and superimposed neuropathic osteoarthropathy and peripheral vascular diseaseperipheral vascular disease
Neuropathic disease can lead to f/x, deformity, bone Neuropathic disease can lead to f/x, deformity, bone production, and hyperemia which can mimic infection production, and hyperemia which can mimic infection on MRI and scanning increasing the false positiveson MRI and scanning increasing the false positives
Peripheral vascular disease can prevent contrast Peripheral vascular disease can prevent contrast material or tracer from reaching site of concern and material or tracer from reaching site of concern and lead to false negativeslead to false negatives
Diagnosis - Diagnosis - osteomyelitisosteomyelitis
Presence of osteomyelitis impacts on Presence of osteomyelitis impacts on failure rate of soft tissue infectionsfailure rate of soft tissue infections
““gold standard” is bone histology and gold standard” is bone histology and culture through non-infected tissueculture through non-infected tissue
ProceduresProcedures
1) Plain films1) Plain films
2) Radionuclide or 2) Radionuclide or Scintigraphic imagingScintigraphic imaging Triple Phase Bone Scan (TPBS)Triple Phase Bone Scan (TPBS) Gallium ScanGallium Scan Indium-111 Leukocyte ScanIndium-111 Leukocyte Scan
3) Magnetic Resonance Imaging (MRI)3) Magnetic Resonance Imaging (MRI)
4) Probe to Bone4) Probe to Bone
ProceduresProcedures
1) 1) Plain filmsPlain films
2) Radionuclide or 2) Radionuclide or Scintigraphic imagingScintigraphic imaging Triple Phase Bone Scan (TPBS)Triple Phase Bone Scan (TPBS) Gallium ScanGallium Scan Indium-111 Leukocyte ScanIndium-111 Leukocyte Scan
3) Magnetic Resonance Imaging (MRI)3) Magnetic Resonance Imaging (MRI)
4) Probe to Bone4) Probe to Bone
X-RayX-RayInitial screening tool:Initial screening tool:
Easily obtained, relatively inexpensive and provides Easily obtained, relatively inexpensive and provides anatomical informationanatomical information
Demineralization, periosteal reaction, bony destruction: Demineralization, periosteal reaction, bony destruction: (the classic triad)(the classic triad)
Appear after 30 – 50% of bone destroyed and can take as Appear after 30 – 50% of bone destroyed and can take as much as 2 weeks to appearmuch as 2 weeks to appear
Found in other conditions such as fracture or deformityFound in other conditions such as fracture or deformity
Sensitivity and specificity approximately 54% and 80%Sensitivity and specificity approximately 54% and 80%
ProceduresProcedures
1) Plain films1) Plain films
2) 2) Radionuclide or Radionuclide or Scintigraphic imagingScintigraphic imaging Triple Phase Bone Scan (TPBS)Triple Phase Bone Scan (TPBS) Gallium ScanGallium Scan Indium-111 Leukocyte ScanIndium-111 Leukocyte Scan
3) Magnetic Resonance Imaging (MRI)3) Magnetic Resonance Imaging (MRI)
4) Probe to Bone4) Probe to Bone
Three-phase bone scintigraphy Three-phase bone scintigraphy (TPBS)(TPBS)
Highly sensitive since positive as early as 24 hours after onsetHighly sensitive since positive as early as 24 hours after onset Focal hyperperfusion, hyperemia, bony uptakeFocal hyperperfusion, hyperemia, bony uptake Can also be seen in fractures, neuropathic joints and Can also be seen in fractures, neuropathic joints and
longstanding cellulitis decreasing specificitylongstanding cellulitis decreasing specificity
Fourth phase (24 hour image) enhances specificityFourth phase (24 hour image) enhances specificity
Concurrent TPBS with IN111 scanning optimalConcurrent TPBS with IN111 scanning optimal
TPBSTPBS Literature review of 20 reports of 1,166 patients Literature review of 20 reports of 1,166 patients
(method of confirmation of osteomyelitis diagnosis (method of confirmation of osteomyelitis diagnosis not specified)not specified)
In patients w/o prior bone changes: 94% sensitive and In patients w/o prior bone changes: 94% sensitive and 85% specific for osteomyelitis85% specific for osteomyelitis
In patients with complicating conditions: 95% In patients with complicating conditions: 95% sensitive, 33% specificsensitive, 33% specific..
Schauwecker et al; The scintigraphic diagnosis of osteomyelitis. AJR 1992; Schauwecker et al; The scintigraphic diagnosis of osteomyelitis. AJR 1992; 158(1):9-18158(1):9-18
Gallium ScanningGallium Scanning Must be performed with a TPBSMust be performed with a TPBS
Diagnostic criteria includeDiagnostic criteria include gallium uptake exceeds TPBS scan uptakegallium uptake exceeds TPBS scan uptake gallium and TPBS scan results are discordantgallium and TPBS scan results are discordant
Sensitivity 81% and specificity 69%Sensitivity 81% and specificity 69%
Cost of gallium scan AND TPBS may exceed cost of a Cost of gallium scan AND TPBS may exceed cost of a single more sensitive and specific test such as an single more sensitive and specific test such as an Indium scan or an MRIIndium scan or an MRI
Schauwecker et al. AJR 158; 9 - 18, January 1992Schauwecker et al. AJR 158; 9 - 18, January 1992
Indium scanningIndium scanning Best sensitivity, specificity, and cost compromise in Best sensitivity, specificity, and cost compromise in
patients with and without prior bone abnormalitiespatients with and without prior bone abnormalities
Issue of practicality of labeling WBCs and later imagesIssue of practicality of labeling WBCs and later images
Does not accumulate at sites that are not infectedDoes not accumulate at sites that are not infected
Compilation of sensitivity and specificity for 142 Compilation of sensitivity and specificity for 142 diabetic subjects from 5 studies showed sensitivity of diabetic subjects from 5 studies showed sensitivity of 88.6% and specificity of 84%88.6% and specificity of 84%
Schauwecker et al. AJR 158; 9 - 18, January 1992Schauwecker et al. AJR 158; 9 - 18, January 1992
ProceduresProcedures
1) Plain films1) Plain films
2) Radionuclide or 2) Radionuclide or Scintigraphic imagingScintigraphic imaging Triple Phase Bone Scan (TPBS)Triple Phase Bone Scan (TPBS) Gallium ScanGallium Scan Indium-111 Leukocyte ScanIndium-111 Leukocyte Scan
3) 3) Magnetic Resonance Imaging (MRI)Magnetic Resonance Imaging (MRI)
4) Probe to Bone4) Probe to Bone
MRI: High-tech, high cost?MRI: High-tech, high cost? Decreased marrow signal intensity on T1-weighted Decreased marrow signal intensity on T1-weighted
images and increased signal intensity on T2-wighted images and increased signal intensity on T2-wighted images with marrow enhancement after injection of images with marrow enhancement after injection of contrastcontrast
Associated findings of soft tissue mass, cortical Associated findings of soft tissue mass, cortical destruction, sequestrum formation and sinus tracts destruction, sequestrum formation and sinus tracts with ulceration increase diagnostic certaintywith ulceration increase diagnostic certainty
Good anatomical detailGood anatomical detail
Sensitivity and specificity comparable to that of Indium Sensitivity and specificity comparable to that of Indium scanscan
Review of 129 diabetics showed MRI sensitivity of 86% Review of 129 diabetics showed MRI sensitivity of 86% and specificity of 84%and specificity of 84%
American College of Radiology: Imaging diagnosis of Osteomyelitis in patients American College of Radiology: Imaging diagnosis of Osteomyelitis in patients with DM/Appropriateness Criteria, 1999with DM/Appropriateness Criteria, 1999
MRI continuedMRI continued 62 feet in 59 patients with suspected osteomyelitis were 62 feet in 59 patients with suspected osteomyelitis were
prospectively evaluated (27 with DM, 35 w/o)prospectively evaluated (27 with DM, 35 w/o)
In DM sensitivity 82%, specificity 80%In DM sensitivity 82%, specificity 80%
In non-DM: sensitivity 89%, specificity 94%In non-DM: sensitivity 89%, specificity 94%
Accuracy increased with contrast-enhanced studies (89%) Accuracy increased with contrast-enhanced studies (89%) vs.78%vs.78%
Cost savings initially because test is more rapidCost savings initially because test is more rapid
Competitively priced compared with combination of TPBS Competitively priced compared with combination of TPBS and Indium or with galliumand Indium or with gallium
Allows good delineation of surgical fieldAllows good delineation of surgical field Morrison, WB et al, Radiology; Aug 1995:196:557-64Morrison, WB et al, Radiology; Aug 1995:196:557-64
TPBS with In-111-labeled WBC TPBS with In-111-labeled WBC scintigraphy in the examination of the feet scintigraphy in the examination of the feet in diabetic patients: Results of Published in diabetic patients: Results of Published
ReportsReportsAuthorAuthor YearYear # patients# patients SensitivitySensitivity SpecificitySpecificity
Seabold Seabold 19931993
1616 80%80% 55%55%
TPBSTPBS++
IN-111 IN-111 WBC ScanWBC Scan
LarcosLarcos19911991
5151 79%79% 78%78%JacobsonJacobson
1991199145*45* 73%73% 91%91%
KeenanKeenan19891989
3939 100%100% 79%79%SchauwekeSchauweke
rr19881988
3535 100%100% 89%89%
MaurerMaurer19861986
1313 75%75% 89%89%
MRIMRI 19991999 129129 86%86% 84%84%
ProceduresProcedures
1) Plain films1) Plain films
2) Radionuclide or 2) Radionuclide or Scintigraphic imagingScintigraphic imaging Triple Phase Bone Scan (TPBS)Triple Phase Bone Scan (TPBS) Gallium ScanGallium Scan Indium-111 Leukocyte ScanIndium-111 Leukocyte Scan
3) Magnetic Resonance Imaging (MRI)3) Magnetic Resonance Imaging (MRI)
4) 4) Probe to BoneProbe to Bone
ProbeProbe 75 subjects with 76 ulcers from one center75 subjects with 76 ulcers from one center
Osteomyelitis diagnosed in 50 (66%), excluded in 26 Osteomyelitis diagnosed in 50 (66%), excluded in 26 Confirmation based on histologic examinationConfirmation based on histologic examination culture data not analyzed as cultures were taken from culture data not analyzed as cultures were taken from
base of infected ulcerbase of infected ulcer if bone biopsy not done, diagnosis was based on if bone biopsy not done, diagnosis was based on
radiographic tests or surgeons finding of purulent radiographic tests or surgeons finding of purulent nonviable bonenonviable bone
Bone probed in 36 of 50 with contiguous osteomyelitis and Bone probed in 36 of 50 with contiguous osteomyelitis and in 4 of 26 w/o osteomyelitisin 4 of 26 w/o osteomyelitis
Sensitivity 66%, specificity 85%, positive predictive value Sensitivity 66%, specificity 85%, positive predictive value 89%, negative 56%89%, negative 56%
Conclusion: Palpation of bone strongly correlated with Conclusion: Palpation of bone strongly correlated with presence osteo. Probing included in initial assessment of presence osteo. Probing included in initial assessment of diabetics with infected ulcers. Specialized imaging studies diabetics with infected ulcers. Specialized imaging studies not necessary if positivenot necessary if positive
Grayson et al JAMA 1995 Mar 1;273(9):721-3Grayson et al JAMA 1995 Mar 1;273(9):721-3
CostCost
ProcedureProcedure Cost (1994)Cost (1994)Plain FilmPlain Film $120$120
TPBSTPBS $550$550
Gallium ScanGallium Scan $1000$1000
Indium ScanIndium Scan $1000$1000
MRIMRI $1000$1000
ConclusionConclusionWhich procedureWhich procedure??
Test Sensitivity Specificity Plain radiographs 54%
(22 - 93%) 80%
50 - 94% TPBS 91%
69 -95% 46%
38 - 100% Indium scan 86%
45 - 100% 84%
67 - 89% TPBS/Indium Scan 88%
(73 – 100%) 82%
(55 – 91%) MRI 92%
29 - 100% 84%
78 - 89% Probe to bone 66% 85%
Data obtained by varying methods and not always comparable. Dependent on the use of bone biopsy to diagnose the disease