Diabetes has become one of the most important medical problems in Europe. An estimated 32 million European adults (5.5% of the population) are believed to have diabetes, and that number is expected to double by 2025.1

Diabetic patients can suffer from associated medical conditions such as renal failure and blindness and are three times more likely to die from cardiovascular disease. About 15% to 20% of patients with diabetes will be hospitalized at some point in their lives because of a foot-related complication. Lower limb amputation is necessary in 10% to 12% of cases, which markedly decreases quality of life.2,3

Clinicians have changed the way the diabetic foot is managed to emphasize prevention.4 Surgical revascularization and partial amputation are becoming viable alternatives to the traditional practice of extensive resection. The possibility of preserving foot functionality creates higher expectations among increasingly well-informed patients. Up to 85% of foot and leg amputations in diabetic patients could be prevented if these patients were treated by a multidisciplinary team with appropriate knowledge of risk factors and treatment options.5

Several pathogenic factors, including sensory neuropathy, ischemia, and infection, contribute to the development of foot ulcers in people with diabetes.6 A variety of imaging techniques, including Doppler ultrasound, CT, scintigraphy, digital angiography, and MR, can provide crucial diagnostic information.

The immune system of diabetic patients predisposes them to certain infections, which may be accompanied by surprisingly mild symptoms.7 Any suspicion of osteomyelitis, foreign bodies, or subcutaneous gas should be initially investigated with radiography. The x-rays will also show arthritis or other skeletal deformities and will be useful for comparison with an ultrasound or MR study.8

Three-phase bone scintigraphy detects osteomyelitis with very high sensitivity, but specificity is low and anatomic resolution is poor, as with all nuclear medicine techniques. Differentiating the diagnosis from trauma or neuropathic joints can be aided by the use of labeled leukocytes.

High-resolution ultrasound is helpful for evaluating whole-body soft-tissue pathologies.9 It is rapid, portable, and noninvasive, and studies can be repeated easily for follow-up. Ultrasound clearly demonstrates abscesses and sinus tracts and can be used to guide aspiration.10 It can also help practitioners study superficial tendons, such as the posterior tibialis, that are often affected in the diabetic foot and may cause deformities.

Evaluation of osseous involvement, however, requires additional imaging. CT helps detect early osseous erosion and depicts sequestrum, foreign bodies, and gas formation. But CT has a lower resolution than MR in detecting bone infection.8 MR should be regarded as the method of choice for assessing the diabetic foot, as it offers 77% to 100% sensitivity and 80% to 100% specificity in the evaluation of osteomyelitis.11

Diabetic patients are unable to detect injuries to their own feet, due to decreased sensory perception. Puncture wounds can go unnoticed until necrosis develops. Repetitive pressure over bony prominences leads to callus formation. These focal cutaneous and subcutaneous prominences are usually found adjacent to metatarsal heads. Calluses show a low signal on T1-weighted MR, variable signal on T2-weighted MR, and diffuse enhancement after paramagnetic contrast injection.11

The callus eventually separates from the underlying dermis to form an ulcer. This disruption to the skin barrier allows infection to spread. MR imaging shows skin ulceration as an interruption of the cutaneous signal line, typically enhancing at the margin. This finding is sometimes extremely subtle, and clinical correlation is essential.

Cellulitis appears as a subcutaneous fat area with poorly defined limits, infected by microorganisms from contiguous skin ulcers. MR depicts such regions with high signal intensity on T2-weighted fat-suppressed images and diffuse enhancement. Diabetic edema located within muscles and subcutaneous tissues is a common finding. It is depicted as high signal on T2-weighted MR and shows no enhancement after gadolinium perfusion. This finding complicates the characterization of osteomyelitis and cellulitis.4

Abscesses are visualized as focal fluid collections with a thick rim of enhancement on postcontrast MR. They are often connected with sinus tracts to the skin or bone. Sinus tracts can be observed as thin lines with a signal similar to fluid and are best detected on postcontrast fat-suppressed T1-weighted MR.11

Septic arthritis and tenosynovitis are also caused by extension/invasion of microorganisms from a skin ulcer. MR imaging shows joint effusion, marginal erosions, reactive subchondral edema, synovial thickening, and enhancement. Osteomyelitis must be suspected if enhancement extends into the medullary bone. This enhancement may correlate with the spread of polymicrobial infection. T1-weighted MR imaging of osteomyelitis shows a loss of normal fatty marrow signal. Edema is seen on T2-weighted fat-suppressed MR, while postcontrast images reveal enhancement (Figure 1).11

Many other pathologies, including fracture, arthritis, recent postsurgical changes, and neuropathic osteoarthropathy, can mimic osteomyelitis on imaging. Diagnosis of osteomyelitis is more likely when the probable site of infection is away from subchondral bone, when MR findings correlate with physical examination and plain film findings, and when signs of associated soft-tissue infection (ulceration, cellulitis, abscesses, and sinus tracts) are seen.

Surgeons generally use MR imaging to determine the extent of required amputation. Because more extensive surgery accelerates the likelihood of contralateral amputation, due to a change in the weight each limb bears, surgeons try to remove only the infected tissue. But soft-tissue involvement often spreads faster than osseous disease, and this should be considered in radiological reports.3

VASCULAR DISEASE

Diabetic patients often have macrovascular (major vessels) and/or microvascular (end vessels) disease. Distal small-vessel disease, which predominates, is difficult to treat.

Vessel wall calcification and stenosis result in chronic lower extremity ischemia.

Ischemia plays an important role in the pathogenesis and poor healing of diabetic foot ulcers, the progression of infection, and development of gangrene.5 Infarcts can occur in the bone marrow. Ischemia also affects other structures and can contribute to progressive tendon degeneration and tears, as well as to arthritis, including neuropathic osteoarthropathy.4 Diabetes masks ischemia, complicating its identification.

Improvements in vascular surgery techniques now enable bypass grafts on small distal vessels. Limb-saving grafts to the foot's arteries have become standard surgical practice and require detailed analysis of the distal vessels on imaging.4

Color-coded duplex arterial ultrasound may be used to screen patients with peripheral vascular disease prior to a complete angiographic study.12 Conventional angiography, on the other hand, may not reveal patent arteries or vessel segments suitable for distal bypass grafting in patients with severe arterial occlusive disease. Selective DSA is regarded as the gold standard for demonstrating the full extent of severe peripheral vascular disease in high-risk patients.13 DSA is an invasive method that carries the risk of potential allergic reactions and kidney failure. Some centers still perform DSA on an inpatient basis, requiring a hospital stay of at least two days.

MR angiography plays an important role in the noninvasive assessment of patients with vascular disease.4,14 It does not use ionizing radiation and involves minimal risk of adverse reaction to contrast and/or renal failure.13 High-resolution techniques are required because of the small size of distal infrapopliteal and pedal vessels. Current high-performance MR systems allow fast imaging and produce high-resolution angiograms with excellent visualization of vessels targeted for distal bypass (Figure 2).

Early diabetes is characterized by increased microvascular pressure and flow. Resultant injury to the microvascular endothelium causes adaptive microvascular sclerosis, which contributes to a loss of vasodilatory reserve and autoregulatory capacity as the disease progresses.15 Considerable evidence suggests that microvascular involvement is a factor in diabetic foot pathology.

Distal ischemia can be evaluated on MR if both pre- and postcontrast sequences are performed (Figure 3). Perfusion measurements permit assessment of vascular integrity in areas where vessels are too small to be imaged directly. Disease in the foot's small vessels can be observed as regional differences in soft-tissue contrast enhancement. Necrotic tissue often appears as a sharply defined nonenhancing area, delineated by an ill-defined enhancing rim that represents reparative or at-risk tissue. Radiologists should bear in mind that osteomyelitis and abscess cannot be diagnosed reliably on MR in nonenhancing areas.16 Documentation of the presence and extent of ischemic and devitalized areas can facilitate surgical planning for debridement and limited foot-sparing amputations.17

Reduced perception of injury, caused by peripheral neuropathy, induces aggressive arthritis with subluxation and bone deformity. This structural deformity and limited joint mobility continues the cycle of abnormal weight-bearing, excessive pressure, and ulceration that forms the classic high-risk scenario for amputation.4 Neuropathic osteoarthropathy is generally reported in the Lisfranc joint, although multiple joints are usually involved.

The acute form of neuropathic osteoarthropathy is generally painless and may mimic cellulitis or deep vein thrombosis on MR (soft-tissue edema, joint effusion, and characteristic subchondral bone marrow enhancement).18 Both osteomyelitis and neuropathic osteoarthropathy can show marrow edema and enhancement, joint effusion, and soft-tissue edema.10 In neuropathic osteoarthropathy, various close joints are similarly affected, with subluxations and marrow edema equal on both sides of the joint. Many diabetic patients have ulceration and osteomyelitis with underlying neuropathic osteoarthropathy at the same time.4

No edema or enhancement is observed in the chronic phase of neuropathic osteoarthropathy, which involves subchondral cysts and bone proliferation, with subluxation (Figure 4). This anatomic deformity leads to altered weight-bearing stress. Calluses form, usually beneath the cuboid bone and over the now dislocated metatarsals.

The diabetic foot is subject to a mixture of vascular, infectious, and neuropathic problems. Imaging provides crucial information for preventive and surgical management, and MR is the best method for detecting osteomyelitis and other related complications.

DR CANGA is chief radiologist in the MRI section, and DR. MARCO DE LUCAS is staff radiologist, both in the diagnostic radiology department of Hospital Universitario Marques de Valdecilla of Santander, Spain. DR. CEREZAL is chair of radiology at Instituto Radiologico Cantabro in Clinica Mompia, Spain.

References

1. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2005: prevalence, numerical estimates, and projections. Diabetes Care 1998;21:1414-1431.

2. Boulton AJ, Vileikyte L. The diabetic foot: the scope of the problem. J Fam Pract 2000;49:3-8.

3. Sanders LJ. Diabetes mellitus: prevention of amputation. J Am Podiatr Med Assoc 1994;84(7):322-328.

4. Morrison WB, Ledermann HP, Schweitzer ME. MR imaging of the diabetic foot. In Update of the Ankle and foot. MRI Clin N Am 2001;(9),3,603-614.

5. Armstrong DG, Lavery LA, Harkless LB. Who is at risk for diabetic foot ulceration? Clin Podiatr Med Surg 1998;15(1):11-19.

6. Caputo GM, Cavanagh PR, Ulbrecht JS, et al. Assessment and management of foot disease in patients with diabetes. NEJM 1994;331(13):854-860.

7. McMahon MM, Bistrian BR. Host defenses and susceptibility to infection in patients with diabetes mellitus. Infect Dis Clin N Am 1995;9(1):1-7.

8. Restrepo CS, Jimenez CR, McCarthy K. Imaging of osteomyelitis and musculoskeletal soft tissue infections: current concepts. Rheum Dis Clin N Am 2003;29(1):89-109.

9. Bureau NJ, Chhem RK, Cardinal E. Musculoskeletal infections: US manifestations. Radiographics 1999;19(6):1585-1592.

10. Loyer EM, DuBrow RA, David CL, et al. Imaging of superficial soft-tissue infections: sonographic findings in cases of cellulitis and abscess. AJR 1996;166:149-152.

11. Morrison WB, Ledermann HP, Schweitzer ME. MR imaging of inflammatory conditions of the ankle and foot. MRI Clin N Am 2001;(9),3,615-637.

12. Hirai T, Ohishi H, Kichikawa K, et al. Ultrasonographic screening for arterial occlusive disease in the pelvis and lower extremities. Radiation Med 1998;16(6):411-416.

13. Kreitner KF, Kalden P, Neufang A, et al. Diabetes and peripheral arterial occlusive disease: prospective comparison of contrast-enhanced three-dimensional MR angiography with conventional digital subtraction angiography. AJR 2000;174:171-179.

14. Goldfarb JW, Hochman MG, Duck Soo K, Edelman RR. Contrast-enhanced MR angiography and perfusion imaging of the hand. AJR 2001;177:1177-1182.

15. Tooke JE. Microvascular function in human diabetes. A physiological perspective. Diabetes 1995;44:721-726.

16. Ledermann HP, Schweitzer ME, Morrison WB. Nonenhancing tissue on MR imaging of pedal infection: characterization of necrotic tissue and associated limitations for diagnosis of osteomyelitis and abscess. AJR 2002;178:215-222.

17. Knox RC, Dutch W, Blume P, Sumpio BE. Diabetic foot disease. Int J Angiol 2000;9:1-6.

18. Caputo GM, Ulbrecht J, Cavanagh PR, Juliano P. The Charcot foot in diabetes: six key points. Am Fam Physician 1998;57(11):2705-2710.