MR Imaging of Bone Marrow Changes in the Diabetic Foot

MR Imaging of Bone Marrow Changes in the Diabetic Foot Poster No.: C-1453 Congress: ECR 2011 Type: Educational Exhibit Authors: E. A. Fatone, T. R. Toledano, A. Cotten, A. Weis, J. Beltran ; 1 1 2 2 3 2 2 3 Chieti/IT, Brooklyn, NY/US, Lille/FR Keywords: MR, Musculoskeletal system DOI: 10.1594/ecr2011/C-1453 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 32

Learning objectives 1) To summarize and provide a pictorial essay of the spectrum of abnormal bone marrow changes in the diabetic foot. 2) To outline MR-based guidelines for distinguishing between osteomyelitis and infected versus non-infected acute neuroarthopathy. Background Diabetic foot complications are responsible for significant morbidity and rising health care costs. MRI is currently considered the modality of choice for imaging of bone marrow signal abnormalities, which represent the earliest as well as primary indication of pathology in the diabetic foot. The radiologist's key role in imaging of the diabetic foot is to differentiate between the common pathologies in this clinical setting, including osteomyelitis, neuroarthrophy, and any overlap between these two. Using our available imaging technology, the ability to distinguish between these entities can directly alter the course of the patient's treatment, and ultimately, the quality of life. Imaging findings OR Procedure details OSTEOMYELITIS Perhaps the most common clinical indication provided to the radiologist for an MRI of the diabetic foot is to exclude osteomyelitis. Because of its ability to provide a complete evaluation of both soft tissue and osseous elements, MRI is currently considered the modality of choice in the evaluation of the diabetic foot when osteomyelitis is suspected. The benefit of MRI in this context lies in its ability to detect early changes in the bone marrow signal, delineating the precise extension of pathology with higher sensitivity and specificity than the remaining imaging modalities. In 90% of all cases, osteomyelitis occurs as a result of direct spread of cutaneous infection, which usually develops at sites of abnormal pressure and consequent skin callus/ulceration, cellulitis, or abscess formation. Due to altered biomechanics in the diabetic foot, often secondary to underlying peripheral neuropathy, these sites predominate in the forefoot (including the plantar aspect of the first and fifth metatarsal Page 2 of 32

heads and the distal first phalanx), and in the hindfoot (at the posterior plantar calcaneus). Midfoot ulceration, when seen, typically presents in the cuboid of patients with a history of neuroarthropathy and foot deformity (FIG 1). The distribution of bone marrow changes in osteomyelitis therefore generally conforms to these sites. Fig.: Osteomyelitis in the midfoot of a patient with history of acute neuroarthropathy: Coronal T1-weighted (left) and STIR (right) images demonstrate concordant loss of T1 signal and STIR hyperintensity in the cuboid, fourth and fifth metatarsals, consistent with osteomyelitis. References: Toledano TR et al. (2011) MRI evaluation of bone marrow changes in diabetic foot: a practical approach pending publication for Semin Musculoskelet Radiol Page 3 of 32

Once a focus of skin infection has been identified, the MRI-based diagnosis of adjacent osteomyelitis hinges on the identification of bone marrow signal abnormality, typified by concordant hypointensity on T1-weighted (w) images and hyperintensity on fluidsensitive images (T2-w, STIR). Post-contrast images will demonstrate enhancement of the affected bone marrow, and can help the radiologist better delineate the ancillary soft tissue disease. (FIG 2-3-4-5). Fig.: Osteomyelitis: Coronal STIR (left) and T1-w (right) images show cortical destruction with concordant T1 hypointensity and STIR hyperintensity consistent with osteomyelitis of the fourth metatarsal and proximal phalanx. Concomitant T1 hypointensity and STIR hyperintensity in the soft tissues at the tip of the fourth ray reflect cellulitis adjacent to a cutaneous ulcer. References: Toledano TR et al. (2011) MRI evaluation of bone marrow changes in the diabetic foot: A practical approach; pending publication in Semin Musculoskelet Radiol Page 4 of 32

Fig.: Osteomyelitis: Sagittal T1-w (left) and fat-suppressed T2-w (right) images show concordant hypointensity on T1 and hyperintensity on T2 in the posterior calcaneus. These findings are consistent with osteomyelitis secondary to direct spread of infection from an adjacent heel ulcer. References: Toledano TR et al. (2011) MRI evaluation of bone marrow changes in the diabetic foot: A practical approach; pending publication in Semin Musculoskelet Radiol Page 5 of 32

Fig.: Osteomyelitis at high pressure points: Coronal T1-w (left) and T2 fat-suppressed (right) images from the same patient as in the previous figure, showing loss of T1 signal with corresponding T2 hyperintensity in the postero-lateral aspect of the calcaneus. References: Toledano TR et al. (2011) MRI evaluation of bone marrow changes in the diabetic foot: A practical approach; pending publication in Semin Musculoskelet Radiol Page 6 of 32

Fig.: Osteomyelitis : Coronal T1-w (left), T2-w (middle) and post-contrast fatsuppressed T1-w (right) images. Concommitant T1-w hypointensity, T2-w hyperintensity, and post-contrast enhancement of the first metatarsal and proximal phalanx are consistent with osteomyelitis. Diffuse enhancement in the adjacent soft tissues reflects associated cellulitis. References: Toledano TR et al. (2011) MRI evaluation of bone marrow changes in the diabetic foot: A practical approach; pending publication in Semin Musculoskelet Radiol REACTIVE BONE MARROW EDEMA Isolated T2 signal hyperintensity without loss of normal T1 signal suggests reactive bone marrow edema. This entity may reflect hyperemia secondary to infection in the adjacent soft tissues (cellulitis, abscesses, septic arthritis) as well as non-infective entities (recent post-surgical changes, acute to subacute fractures, neuroarthopathy) (FIG 6). In all of these cases, the subsequent development of any changes on the T1-w images should raise suspicion for superimposed osteomyelitis. Page 7 of 32

Fig.: Reactive bone marrow edema versus osteomyelitis: Coronal fat-suppressed T2-w (left) and T1-w (right) images. Isolated T2-w hyperintensity in the mid to distal fourth metatarsal without corresponding hypointensity on the T1-w image (blue ovals) is consistent with reactive marrow edema. In contrast, cortical disruption and T1-w hypointensity in the distal first, third, and fourth metatarsals represent osteomyelitis. References: Toledano TR et al. (2011) MRI evaluation of bone marrow changes in the diabetic foot: A practical approach; pending publication in Semin Musculoskelet Radiol SEPTIC ARTHRITIS Like osteomyelitis, septic arthritis is most often the result of direct spread of adjacent soft tissue infection. Typical findings described for septic arthritis include bony erosions, chondral destruction, thickened and intensely enhancing synovium with perisynovial soft tissue edema, and joint effusions which may communicate with a sinus tract (fig 7). In addition to these findings, reactive marrow edema is often seen in the subchondral bone at the affected joint, which may be confusing when evaluating for osteomyelitis. In comparison to osteomyelitis, however, this edema should present as a thin rim of isolated T2 hyperintensity confined to the subchondral marrow, without a hypointense correlate on T1-w images. Extension of edema proximal to the subchondral bone and diffuse T1-w hypointensity in the adjacent marrow should raise suspicion for superimposed osteomyelitis. Page 8 of 32

Fig.: Septic arthritis complicating cellulitis: Post-contrast fat-suppressed coronal T1w images demonstrate thickened and intensely enhancing synovium in the fourth metatarsophalangeal joint (white arrows) with enhancement in the surrounding soft tissues. Findings are consistent with septic arthritis secondary to direct spread via the adjacent sinus tract extending from the skin surface (white triangle). References: Toledano TR et al. (2011) MRI evaluation of bone marrow changes in the diabetic foot: A practical approach; pending publication in Semin Musculoskelet Radiol ASSOCIATED SOFT TISSUE FINDINGS As discussed above, assessment of the diabetic foot for signs of osteomyelitis should always involve careful inspection of the overlying soft tissues. Helpful secondary soft tissue findings which support the marrow-based diagnosis of osteomyelitis include skin callus/ulceration, cellulitis, abscess, and sinus tract formation. In addition to demonstrating enhancement of abnormal bone marrow, post-contrast images will better delineate any ancillary soft tissue findings (fig 8-9). This, in turn, will allow more precise pre-operative planning where indicated, limiting unnecessary debridement or amputation. Page 9 of 32

Fig.: Associated soft tissue findings of osteomyelitis: Fat-suppressed post-contrast sagittal T1-w images. Enhancement of the distal fourth metatarsal and proximal phalanx, which showed corresponding T1 hypointensity and T2 hyperintensity on precontrast images, reflects osteomyelitis. Secondary soft tissue findings shown here include diffuse soft tissue enhancement centered on the fourth ray (cellulitis) and a focal rim enhancing fluid collection (white arrow) in the soft tissues adjacent to the head of the proximal fourth phalanx (abscess). A sinus tract leading directly from the inflamed plantar soft tissues to the fourth metatarsophalangeal joint (white triangle), Page 10 of 32

in conjunction with synovial and periarticular enhancement, reflects associated septic arthritis. References: Toledano TR et al. (2011) MRI evaluation of bone marrow changes in the diabetic foot: A practical approach; pending publication in Semin Musculoskelet Radiol Fig.: Associated soft tissue findings of osteomyelitis: Coronal (left) and sagittal (left) fat-suppressed post-contrast T1-w images show two rim enhancing fluid collections consistent with abscesses (white arrows). One of these is in direct proximity with a fracture of the proximal phanx (dashed arrow), which demonstrated evidence of osteomyelitis on unenhanced T1- and T2-w images. Also note the presence of an ulcer (white triangle) with adjacent cellulitis along the plantar aspect of the first ray. References: Toledano TR et al. (2011) MRI evaluation of bone marrow changes in the diabetic foot: A practical approach; pending publication in Semin Musculoskelet Radiol NEUROPATHIC OSTEOARTHROPATHY The most common and confounding MRI mimic of osteomyelitis in the diabetic foot is neuropathic (Charcot) osteoarthropathy, which usually presents in patients who have suffered diabetes for greater than 10 years. The atrophic or acute resorptive form represents a hyperemic, osteolytic process which predominates in the metatarsophalangeal joints and the forefoot. The classic radiologic findings are of osseous resorption at the metatarsophalangeal joints, leading to partial or complete disappearance of the metatarsal heads and proximal phalanges, with classic "pencil point" or "sucked candy stick" tapering (fig 10). In contrast, the hypertrophic Page 11 of 32

or "reparative" stage of neuroarthropathy is characterized by sclerosis, osteophyte formation, severe degenerative change, and eventually joint destruction. Page 12 of 32

Fig.: Atrophic neuroarthropathy: Coronal T1-w image demonstrates resorptive changes of "pencil-point" or "sucked candy-stick" tapering of the distal second and third metatarsals (white arrows), a classic finding of atrophic neuroarthropathy. References: Toledano TR et al. (2011) MRI evaluation of bone marrow changes in the diabetic foot: A practical approach; pending publication in Semin Musculoskelet Radiol In order to diagnose diabetic neuropathy on MRI, it is essential to understand the radiologic timeline of disease. The MRI findings in the acute stage of neuroarthropathy are the most confounding for osteomyelitis. These include soft tissue edema, joint effusions, fluid collections, and periarticular soft tissue enhancement. Bone marrow signal abnormalities at this stage include subchondral T2-w hyperintensity and T1-w hypointensity, as well as post-contrast enhancement of the marrow - all of which are findings also seen in osteomyelitis. The subacute stage of neuroarthropathy may be associated with bone resorption, erosion, and fragmentation, as well as subchondral cyst formation (fig 11). Page 13 of 32

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Fig.: Subacute neuroarthropathy: Sagittal fat-suppressed T1-w image shows subchondral cyst formation (white arrow) and irregular cortical margins at the joint of Lisfranc, typical findings for uncomplicated subacute neuroarthropathy. References: Toledano TR et al. (2011) MRI evaluation of bone marrow changes in the diabetic foot: A practical approach; pending publication in Semin Musculoskelet Radiol The chronic stage is typified by a deformed foot which maintains normal density and little bone marrow edema, with the classic constellation of destruction, debris, disorganization, dislocation, and density. In an uncomplicated neuropathic joint at this stage, the bone marrow is typically hypointense on all sequences, compatible with sclerosis, and any abnormal hyperintensity in the bone marrow or cortex should raise suspicion for superimposed infection (or recent fractures related to the neuropathy). DISTINGUISHING OSTEOMYELITIS FROM NEUROARTHROPATHY When discriminating the bone marrow changes of neuroarthropathy from those of osteomyelitis, the first clue lies in the distribution of pathology. As described above, osteomyelitis almost always occurs as a result of direct spread of cutaneous infection, usually at predictable sites of ulceration throughout the foreand hindfoot. Regardless of the location, findings of abnormal bone marrow signal without a contiguous focus of soft tissue pathology point away from osteomyelitis. Neuroarthropathy, on the other hand, is essentially an articular disease, which can occur at any joint but predominates in the midfoot and most commonly involves the Lisfranc and Chopart joints. The common distributions of neuroarthropathy and osteomyelitis therefore oppose each other, favoring the midfoot in neuroarthropathy and the fore- and hindfoot in osteomyelitis. When osteomyelitis is seen in the midfoot, it typically involves the cuboid of severely neuropathic patients. In addition, neuropathic arthropathy tends to affect multiple joints within the foot, while osteomyelitis remains a local or contiguously spreading infection. Therefore, while bone marrow edema is a hallmark of both neuroarthropathy and osteomyelitis, a midfoot, subchondral, periarticular, and/or polyarticular distribution of findings without contiguous soft tissue pathology would favor neuroarthropathy over osteomyelitis (Fig 12). Page 15 of 32

Fig.: Neuroarthropathy versus osteomyelitis: Coronal T1-w (left) and fat-suppressed post-contrast T1-w (right) images show concordant T1 hypointensity (white arrow) and post-contrast enhancement (white dashed arrow) in a periarticular, subchondral location at the joint of Lisfranc. The location of these findings as well as the absence of any adjacent soft tissue pathology favor the diagnosis of neuroarthropathy over osteomyelitis. References: Toledano TR et al. (2011) MRI evaluation of bone marrow changes in the diabetic foot: A practical approach; pending publication in Semin Musculoskelet Radiol INFECTED VERSUS NON-INFECTED NEUROARTHROPATHY Multiple parameters of deviant bone marrow signal have been effectively used to diagnose infection superimposed on acute neuropathy. Diffuse bone marrow signal abnormality, to the extent of absent normal marrow throughout the entire bone, is significantly more common in the context of acute infection. In addition, the more intense and geographically distant the bone marrow signal abnormality from the articular surface, the higher the likelihood of superimposed infection. Subchondral cysts have been commonly found in the sterile neuropathic joint but are significantly rare in the presence of superinfection, and by extension, will "disappear" on serial imaging obtained Page 16 of 32

during the development of osteomyelitis. In addition, Schweitzer et al have described the "Ghost Sign," in which bones with superimposed osteomyelitis are indistinct ("disappear") on T1-w sequences, only to become more discrete ("reappear") on fluid-sensitive or postcontrast T1-w images (FIG 13). Fig.: Neuroarthropathy with superimposed osteomyelitis: The "Ghost Sign." Sagittal T1-w (left) image demonstrates diffuse loss of normal T1 signal in the bone marrow of the hindfoot and midfoot, with apparent "disappearance" of the distal tibia, a large portion of the talus, the anterior calcaneus, and the cuboid. Fat suppressed postcontrast T1-w image (right) shows "re-appearance" of the same osseous structures, compatible with the "Ghost Sign" of superinfected neuroarthropathy. References: Toledano TR et al. (2011) MRI evaluation of bone marrow changes in the diabetic foot: A practical approach; pending publication in Semin Musculoskelet Radiol Images for this section: Page 17 of 32

Fig. 1: Osteomyelitis in the midfoot of a patient with history of acute neuroarthropathy: Coronal T1-weighted (left) and STIR (right) images demonstrate concordant loss of T1 signal and STIR hyperintensity in the cuboid, fourth and fifth metatarsals, consistent with osteomyelitis. Page 18 of 32

Fig. 2: Osteomyelitis: Coronal STIR (left) and T1-w (right) images show cortical destruction with concordant T1 hypointensity and STIR hyperintensity consistent with osteomyelitis of the fourth metatarsal and proximal phalanx. Concomitant T1 hypointensity and STIR hyperintensity in the soft tissues at the tip of the fourth ray reflect cellulitis adjacent to a cutaneous ulcer. Page 19 of 32

Fig. 3: Osteomyelitis: Sagittal T1-w (left) and fat-suppressed T2-w (right) images show concordant hypointensity on T1 and hyperintensity on T2 in the posterior calcaneus. These findings are consistent with osteomyelitis secondary to direct spread of infection from an adjacent heel ulcer. Page 20 of 32

Fig. 4: Osteomyelitis at high pressure points: Coronal T1-w (left) and T2 fat-suppressed (right) images from the same patient as in the previous figure, showing loss of T1 signal with corresponding T2 hyperintensity in the postero-lateral aspect of the calcaneus. Fig. 5: Osteomyelitis with ancillary soft tissue findings: Coronal T1 weighted (left), T2 weighted (middle) and post-contrast fat-suppressed T1 weighted (right) images. Concommitant loss of T1 signal, T2-weighted hyperintensity, and postcontrast enhancement of the 1st metatarsal and proximal phalanx are consistent with Page 21 of 32

osteomyelitis. Diffuse enhancement in the adjacent soft tissues is consistent with cellulitis. Fig. 6: Reactive bone marrow edema versus osteomyelitis: Coronal fat-suppressed T2-w (left) and T1-w (right) images. Isolated T2-w hyperintensity in the mid to distal fourth metatarsal without corresponding hypointensity on the T1-w image (blue ovals) is consistent with reactive marrow edema. In contrast, cortical disruption and T1-w hypointensity in the distal first, third, and fourth metatarsals represent osteomyelitis. Page 22 of 32

Fig. 7: Septic arthritis complicating cellulitis: Post-contrast fat-suppressed coronal T1w images demonstrate thickened and intensely enhancing synovium in the fourth metatarsophalangeal joint (white arrows) with enhancement in the surrounding soft tissues. Findings are consistent with septic arthritis secondary to direct spread via the adjacent sinus tract extending from the skin surface (white triangle). Page 23 of 32

Fig. 8: Associated soft tissue findings of osteomyelitis: Fat-suppressed post-contrast sagittal T1-w images. Enhancement of the distal fourth metatarsal and proximal phalanx, which showed corresponding T1 hypointensity and T2 hyperintensity on pre-contrast images, reflects osteomyelitis. Secondary soft tissue findings shown here include diffuse soft tissue enhancement centered on the fourth ray (cellulitis) and a focal rim enhancing fluid collection (white arrow) in the soft tissues adjacent to the head of the proximal fourth phalanx (abscess). A sinus tract leading directly from the inflamed plantar soft tissues Page 24 of 32

to the fourth metatarsophalangeal joint (white triangle), in conjunction with synovial and periarticular enhancement, reflects associated septic arthritis. Fig. 9: Associated soft tissue findings of osteomyelitis: Coronal (left) and sagittal (left) fat-suppressed post-contrast T1-w images show two rim enhancing fluid collections consistent with abscesses (white arrows). One of these is in direct proximity with a fracture of the proximal phanx (dashed arrow), which demonstrated evidence of osteomyelitis on unenhanced T1- and T2-w images. Also note the presence of an ulcer (white triangle) with adjacent cellulitis along the plantar aspect of the first ray. Page 25 of 32

Fig. 10: Atrophic neuroarthropathy: Coronal T1-w image demonstrates resorptive changes of "pencil-point" or "sucked candy-stick" tapering of the distal second and third metatarsals (white arrows), a classic finding of atrophic neuroarthropathy. Page 26 of 32

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Fig. 11: Subacute neuroarthropathy: Sagittal fat-suppressed T1-w image shows subchondral cyst formation (white arrow) and irregular cortical margins at the joint of Lisfranc, typical findings for uncomplicated subacute neuroarthropathy. Fig. 12: Neuroarthropathy versus osteomyelitis: Coronal T1-w (left) and fat-suppressed post-contrast T1-w (right) images show concordant T1 hypointensity (white arrow) and post-contrast enhancement (white dashed arrow) in a periarticular, subchondral location at the joint of Lisfranc. The location of these findings as well as the absence of any adjacent soft tissue pathology favor the diagnosis of neuroarthropathy over osteomyelitis. Page 28 of 32

Fig. 13: Neuroarthropathy with superimposed osteomyelitis: The "Ghost Sign." Sagittal T1-w (left) image demonstrates diffuse loss of normal T1 signal in the bone marrow of the hindfoot and midfoot, with apparent "disappearance" of the distal tibia, a large portion of the talus, the anterior calcaneus, and the cuboid. Fat suppressed post-contrast T1-w image (right) shows "re-appearance" of the same osseous structures, compatible with the "Ghost Sign" of superinfected neuroarthropathy. Page 29 of 32

Conclusion Abnormal bone marrow signal is the hallmark of the diabetic foot. One of the most important roles of MRI in the imaging workup of the diabetic foot is to be able to distinguish the common and often comorbid pathologies which are reflected by deviant bone marrow signal, most of which share the common denominator of T2-w signal hyperintensity. The primary diagnostic challenges in this setting are to distinguish osteomyelitis from reactive bone marrow edema, neuroarthropathy from osteomyelitis, and the sterile from the superinfected neuropathic joint. In approaching the pattern of bone marrow abnormalities in the diabetic foot, the first consideration should be the geographic distribution of pathology. A midfoot, subchondral, and periarticular distribution of findings in the absence of a contiguous focus of skin disruption, most commonly at the Lisfranc or Chopart joints, would strongly support neuroarthropathy. On the other hand, a forefoot focus of abnormal bone marrow away from the subchondral surface and adjacent to a skin ulcer, abscess, or sinus tract would be indicative of osteomyelitis. One should also consider whether the pathology involves many joints within a region, which would favor neuroarthropathy, versus a local process which spreads contiguously, which typifies osteomyelitis. In the cases where neuroarthropathy has already been diagnosed, parameters of bone marrow abnormality which have been successfully correlated with superimposed infection include diffusely abnormal bone marrow, progressive subarticular enhancement, loss of subchondral cysts, and a positive MRI "Ghost Sign." Application of these criteria should help successfully guide the clinician towards the appropriate therapeutic approach, ultimately minimizing foot deformity and optimizing quality of life for the patient. Personal Information References 1. Russell JM, Peterson JJ, Bancroft LW. MR Imaging of the Diabetic Foot. Magn Reson Imaging Clin N Am 2008;16:59-70. Page 30 of 32

2. Donovan, A, Schweitzer ME. Current concepts in imaging diabetic pedal osteomyelitis. Radiol Clin N Am 2008; 46:1105-1124. 3. American College of Radiology ACR Appropriateness Criteria, Suspected Osteomyelitis of the Foot in Patients with Diabetes Mellitus, 2008. 4. Ledermann HP, Morrison WB, Schweitzer ME. MR image analysis of pedal osteomyelitis: distribution, patterns of spread, and frequency of associated ulceration and septic arthritis. Radiology 2002;223:747-755. 5. Collins MS, Schaar MM, Wenger DE, Mandrekar JN. T1-weighted MRI characteristics of pedal osteomyelitis. Am J Roentgenol 2005;185:386-93. 6. Johnson PW, Collins MS, Wenger DE. Diagnostic utility of T1-weighted characteristics in evaluation of osteomyelitis of the foot. Am J Roentgenol 2009;192:96-100. 7. Tomas MB, Patel M, Marwin SE, Palestro CJ. The diabetic foot. Br J Radiol 2000;73:443-50. 8. Chatha DS, Cunningham PM, Schweitzer ME. MR Imaging of the Diabetic Foot: Diagnostic Challenges. Radiol Clin N Am 2005;43:747-759. 9. Schweitzer ME, Morrison WB. MR imaging of the diabetic foot. Radiol Clin N Am 2004;42:61-71. 10. Ledermann HP, Morrison WB. Differential diagnosis of pedal osteomyelitis and diabetic neuroarthropathy: MR imaging. Seminars in Musculoskeletal Radiology 2005; 9(3):272-283. 11. Tan PL, Teh J. MRI of the diabetic foot: differentiation of infection from neuropathic change. Br J Radiol. 2007;80:939-48. 12. Donovan A, Schweitzer ME. Use of MR imaging in diagnosing diabetes-related pedal osteomyelitis. Radiographics 2010;30:723-736. 13. Mueller MJ, Minor SD, Diamond JE. Relationship of foot deformity to ulcer location in patients with diabetes mellitus. Phys Ther 1990;70:356-62. Page 31 of 32

14. Ramesh S, Santh LG, Panchapakesa RC, Rukmangatha RS,Vasanthi N. Diabetic forefoot neuroarthropathy - "Sucked candy stick" appearance. J Indian Rheumatol Assoc 2003;11:55-58. 15. Chatha DS, Cunningham, PM, Schweitzer, ME. MR imaging of the diabetic foot. Radiol Clin N Am 2005;43:747-759. 16. Ahmadi ME, Morrison WB, Schweitzer ME, Carrino JA, Raikin SM, Ledermann HP. Neuropathic arthropathy of the foot with and without superimposed osteomyelitis: MR imaging characteristics. Radiology 2006;238:622-631. Page 32 of 32