Imaging Assessment of Imaging Assessment of Diabetic Foot InfectionsDiabetic Foot Infections

Regina Alivisatos, MDRegina Alivisatos, MD

Medical Officer Medical Officer

DSPIDPsDSPIDPs

IntroductionIntroduction

Patients with osteomyelitis should be identifiedPatients with osteomyelitis should be identified

in 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 have

osteomyelitisosteomyelitis 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 Date

DiagnostiDiagnostic c

ProcedureProcedure

ApplicationsApplications*done at investigator’s discretion*done at investigator’s discretion

AA BB CC DD EE FF GG

X/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 Highly sensitive since positive as early as 24 hours after onsetonset

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 In patients w/o prior bone changes: 94% sensitive and 85% specific for osteomyelitisand 85% 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 Sensitivity and specificity comparable to that of Indium scanIndium scan

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

ReportsReports

AuthorAuthor YearYear # patients# patients SensitivitySensitivity SpecificitySpecificity

Seabold Seabold

199319931616 80%80% 55%55%

TPBSTPBS

++

IN-111 IN-111 WBC ScanWBC Scan

LarcosLarcos

199119915151 79%79% 78%78%

JacobsonJacobson

1991199145*45* 73%73% 91%91%

KeenanKeenan

198919893939 100%100% 79%79%

SchauwekeSchauwekerr

19881988

3535 100%100% 89%89%

MaurerMaurer

198619861313 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 Bone probed in 36 of 50 with contiguous osteomyelitis and in 4 of 26 w/o osteomyelitisand in 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 diabetics with infected ulcers. Specialized imaging studies not necessary if positivestudies not 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