Establishment Of A Hemodynamics Model Of Diabetic Lower Extremity Vascular Disease Based On ^99mTc-MIBI Imaging

Background and objectiveDiabetic vascular disease of lower extremities,also known as diabetic lower extremity artery disease（LEAD）,is one of the most frequent diabetic complications that are characterized with the widespread atherosclerosis.Continuous hyperglycemia contributes to the varying degree of stenosis and occlusion,a process that results in hypoxia and ischemia and finally,evoking major adverse cardiovascular events（MACE）,such as myocardial infarction,stroke,and cardiovascular death.Ankle-brachial Index（ABI）,computed tomography angiography（CTA）,ultrasonography,magnetic resonance angiography（MRA）,and digital subtraction angiography（DSA）are mainly focus on atherosclerosis lesions or the changes of blood flow,meanwhile,they cannot distinguish the early hypoperfusion of the microcirculation.Whereas early LEAD in diabetes mellitus is mainly associated with microcirculatory dysfunction,Therefore,a mathematical model that based on the pivotal parameters of microvascular hemodynamics and microcirculation perfusion was constructed to discriminate the dysfunction of microcirculation in hoping of the early diagnosis and intervention.Subjects and MethodsSubjectsFifty-seven participants,including 14 volunteers（Cont,no history of diabetes and normal ABI）,27 patients with diabetes（DM,diabetes patients with normal ABI）,and 16diabetics with LEAD(（LEAD＿DM,diabetes patients with LEAD）,were enrolled in this study from September 2019 to July 2021.Informed consents were obtained from all the participants.MethodsThe clinical characteristics,such as smoking history,age,sex,weight,waist circumference,height,body mass index（BMI）,course of diabetes mellitus and hypertension,were collected.The glycosylated hemoglobin blood glucose（Hb A1c）,fasting plasma glucose（FPG）,blood lipid which including high-density lipoprotein cholesterol（HDL-c）,total cholesterol（TC）et al.,ankle-brachial index（ABI）,and toe-brachial index（TBI）were measured.All the participants underwent ^99mTc-MIBI scintigraphy and the measurement of ABI,the perfusion ratio of the leg,and the perfusion ratio of the thigh were obtained via analyzing the images and calculating the perfusion ratio of the leg.The lower-extremity perfusion assessment（LEPA）model was constructed by the pharmacokinetic compartment model and the systemic distribution rate of the injected,using k₁₂,k₁₃to obtain basal perfusion index（BPI）and using k₀,k_a,k₁₂,k₂₁,k₁₃,k₃₁to obtain the active perfusion index（API）,to use these two parameters to characterize the lower extremity perfusion status,we further clarified the clinical significance of the parameters.BPI can be considered as an indicator of lower-extremity perfusion ability in the basal state,API can be considered to indicate the ability of the change to meet the increased activity demand in the lower-extremity perfusion.Next,the API and BPI of each group were analyzed and compared with the traditional ABI.The limb perfusion values（API and BPI）showed substantial consistency with the actual measured data（ABI）.Moreover,the new discriminant rules were proposed by calculating the probability density function of API and BPI.The model parameters（API and BPI）evaluating lower-extremity ischemia can group the patients correctly,can maximize the identification of patients with lower-extremity ischemia and reduce missed diagnosis.Then,four representative patients from the LEAD＿DM group were selected to evaluated their clinical manifestations.The LEPA model explained the phenomenon using perfusion kinetics indices（API,BPI）in clinical practice,many diabetes patients with severe vascular stenosis show no or only mild symptoms of limb ischemia,while some patients with normal ABI present with typical ischemia symptoms.Results1.The control groups had no metabolic and cardiovascular diseases,and no risk factors of peripheral arterial disease.There were no differences in body mass index,blood lipids,glycated hemoglobin,fasting glucose and high-sensitivity C-reactive Protein between the diabetic group（with normal ABI）and those with LEAD diabetes.2.The values of estimated limb perfusion in the LEPA model were consistent with the actual measured data.The lower limb perfusion in diabetes（DM,diabetes patients with normal ABI）group（BPI:106.21±11.99,API:12.34±3.27）was significantly decreased when compared with the control group（BPI:141.56±17.38,API:14.56±3.12）（P<0.05）.Diabetes with LEAD group（BPI:47.85±20.30,API:7.06±1.70）had a more severe reduction in lower extremity perfusion than those without LEAD（BPI:106.21±11.99,API:12.34±3.27）（P<0.05）.3.The reductions of lower limb perfusion in diabetic patients（DM,diabetes patients with normal ABI）could be discriminated earlier using the LEPA model.On the basis of these new discriminant rules,all 16 patients in the LEAD＿DM group were correctly diagnosed.While five of the 27 patients in the DM group were classified into the LEAD＿DM groups.4.API and BPI had high sensitivity（100%）and a certain specificity（80.77%）for early diagnosis of LEAD.Conclusions1.In this study,the ankle-brachial index（ABI）and ^99mTc-MIBI scintigraphy data were collected,and a LEPA model was established based on the pharmacokinetics hemodynamics features,the microvascular hypoperfusion of lower limbs in diabetic patients could be successfully identified using the LEPA model.2.LEPA model can describe the changes of muscle perfusion in lower extremity more comprehensively.The model parameters（API and BPI）reflect the characteristics of microvascular perfusion dynamics,and provide the basis for the diagnosis of early diabetic lower extremity vascular disease,it has good clinical effect and is helpful for early diagnosis and intervention of high-risk population.