Clinical characteristics
A total of 103 patients (67 [55–74] years, 76 men and 27 women) underwent lower-limb perfusion scintigraphy with quantitative SPECT/CT. Conventional planar images were obtained for 38 patients (68 [58–73] years, 29 men and 9 women). Patient characteristics, including medical histories, comorbidities, and blood examination results, are presented in Table 2.
Of the total, 54 patients were clinically diagnosed as having LLOM (LLOM group), while 49 were clinically diagnosed as not having LLOM (non-LLOM group). Table 3 shows patient characteristics for the two groups. Out of 54 patients in the LLOM group, 49 were clinically identified as having CE (LLOM-CE group) and 5 patients were clinically identified as having only LLOM (LLOM only group). In addition, 32 patients were clinically diagnosed with CE only (CE only group) and 17 patients were clinically diagnosed as negative for both LLOM and CE (negative group) (Table 4).
-Visual assessment using Ga-scintigraphy
Based on a visual assessment using planar images, 12 patients (71%) from the LLOM group and 14 patients (67%) from the non-LLOM group were rated as positive for LLOM. SPECT images identified 43 patients (79%) from the LLOM group and 32 patients (65%) from the non-LLOM group as positive for LLOM. CT images categorized 37 patients (69%) from the LLOM group and 4 patients (8%) from the non-LLOM group as positive for LLOM. SPECT/CT images identified 44 patients (81%) from the LLOM group and 4 patients (8%) from the non-LLOM group as positive for LLOM.
Out of the LLOM-CE group, 45 patients (92%), 34 patients (69%) and 39 patients (80%) were rated as positive for LLOM based on planar, CT and SPECT images, respectively (Table 4). Out of the LLOM only group, 4 patients (80%), 3 patients (60%) and 4 patients (80%) were rated as positive for LLOM based on planar, CT and SPECT images, respectively. Out of the CE only group, 32 patients (100%), 3 patients (9%) and 26 patients (81%) were rated as positive for LLOM based on planar, CT and SPECT images, respectively. Out of the negative group, 8 patients (47%), 1 patient (6%) and 6 patients (35%) were rated as positive for LLOM based on planar, CT and SPECT images, respectively.
-Quantitative assessment using Ga-scintigraphy
Based on clinical diagnosis, IBR, SUVmax, and TLU for the LLOM group were 12.23 (7.38–17.94), 4.85 (3.45–8.31), and 68.77 (22.90–96.63), respectively, and 1.00 (1.00–1.47), 1.34 (1.14–1.62), and 8.63 (1.15–2.33), respectively, for the non-LLOM group (Table 3). The cut-off values for diagnosing LLOM were 1.99 for IBR, 1.74 for SUVmax, and 7.29 for TLU.
The IBR, SUVmax, and TLU in the LLOM-CE group were 14.86 (8.91–17.40), 6.36 (3.45–8.35), and 69.80 (22.60–96.99), respectively. The IBR, SUVmax, and TLU in the LLOM-only group were 9.13 (5.40–8.87), 4.88 (2.02–4.87), and 58.66 (35.02–76.34), respectively. The IBR, SUVmax, and TLU in the CE-only group were 2.24 (1.00–1.01), 1.56 (1.14–1.58), and 8.51 (1.31–2.36), respectively. The IBR, SUVmax, and TLU in the negative group were 1.86 (1.00–1.01), 1.58 (1.14–1.49), and 8.87 (1.09–2.30), respectively. The results demonstrated statistically significant differences in IBR, SUVmax, and TLU between the LLOM-CE and CE-only groups (p < 0.001 for all three quantitative parameters).
Accuracy of imaging methods
As shown in Table 5, the sensitivity and specificity of the planar images were 71% and 33%, respectively. The sensitivity and specificity of the SPECT images were 80% and 35%, respectively. The sensitivity and specificity of the CT images were 69% and 92%, respectively. The sensitivity and specificity of SPECT/CT without quantitative analysis were 81% and 92%, respectively.
The sensitivity and specificity of SPECT/CT with IBR were 91% and 96%, respectively. The sensitivity and specificity of SPECT/CT with SUVmax were 89% and 94%, respectively. The sensitivity and specificity of SPECT/CT with TLU were 91% and 92%, respectively. The areas under the ROC curves for the presence of LLOM were 0.957 using IBR, 0.921 using SUVmax, and 0.926 using TLU.
Patient prognoses
MAE occurred in 23 patients with LLOM (43%). The area under the ROC curve for MAE occurrences was 0.680 for TLU, and the cut-off values for prognosis prediction were 38.35 for TLU. The prevalence of diabetes mellitus and chronic kidney disease as well as WBC, IBR, and TLU were statistically significantly higher among patients who experienced an MAE (Table 6). The results of the Cox proportional hazards regression analyses are presented in Table 7. The univariate analysis revealed significant correlations for WBC (p = 0.002), diabetes mellitus (p = 0.012), TLU (p = 0.020), IBR (p = 0.030), and chronic kidney disease (p = 0.049). A multivariate analysis was performed for the top four parameters and demonstrated a statistically significant positive correlation between WBC and MAE (p = 0.003) as well as TLU and MAE (p = 0.047), while IBR showed no statistical significance (p = 0.175).
Case studies
Figure 2 shows a case of a patient with low TLU. This 68-year-old man developed a fever and increased inflammatory markers after treatment for severe leg trauma. Pretreatment Ga-scintigraphy was conducted, and planar images showed no clear signs of accumulation in the left toes. However, SPECT/CT images revealed increased subcutaneous density and accumulation, indicating CE, around the 4th distal phalanx of the left foot and destruction and mild accumulation in the bone, indicating LLOM. Quantitative analyses were performed using GI-BONE and showed a low SUVmax of 3.25, low IBR of 5.40, and low TLU of 35.02. Recovery from fever and inflammation was smooth, not requiring surgical treatment. This patient did not experience an MAE within the 3-year observation period.
Figure 3 shows a case of a patient with high TLU. This 68-year-old man was treated for diabetic gangrene and underwent Ga-scintigraphy to confirm the diagnosis. SPECT/CT images revealed increased subcutaneous density and accumulation indicative of CE near the right 1st proximal phalanx and metatarsal, with bone destruction and distinct accumulation indicative of LLOM. Quantitative analyses using GI-BONE found a low SUVmax of 3.45, high IBR of 12.0, and high TLU of 133.76. Minor amputation was performed, and sequestrum in the affected areas during operation confirmed the diagnosis of LLOM. These findings indicated that the lesion had active chronic inflammation. Thirty-nine days after the initial Ga-scintigraphy, the patient experienced a fatal event.