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Graphs depicting relationships between T2* in the anterior (a), lateral (b), soleus (c), and gastrocnemius (d) muscle groups and ABI in PAD patients. Significant correlations were observed for all muscle groups, with Spearman rank correlation coefficients (ρ) of 0.837, 0.820, 0.785, and 0.644, respectively 

Graphs depicting relationships between T2* in the anterior (a), lateral (b), soleus (c), and gastrocnemius (d) muscle groups and ABI in PAD patients. Significant correlations were observed for all muscle groups, with Spearman rank correlation coefficients (ρ) of 0.837, 0.820, 0.785, and 0.644, respectively 

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Background: Noninvasive cardiovascular magnetic resonance (CMR) techniques including arterial spin labeling (ASL), blood oxygenation level-dependent (BOLD), and intravoxel incoherent motion (IVIM), are capable of measuring tissue perfusion-related parameters. We sought to evaluate and compare these three CMR techniques in characterizing skeletal m...

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... rank correlation analysis showed that in PAD patients, T2* was significantly correlated with ABI in the anterior (ρ = 0.837; P < 0.001), lateral (ρ = 0.820; P < 0.001), soleus (ρ = 0.785; P = 0.001), and gastrocnemius (ρ = 0.644; P = 0.012) muscle groups (Fig. 5), whereas no significant correlation was observed for the other param- eters (all P > ...
Context 2
... rank correlation analysis showed that in PAD patients, T2* was significantly correlated with ABI in the anterior (ρ = 0.837; P < 0.001), lateral (ρ = 0.820; P < 0.001), soleus (ρ = 0.785; P = 0.001), and gastrocnemius (ρ = 0.644; P = 0.012) muscle groups (Fig. 5), whereas no significant correlation was observed for the other param- eters (all P > ...

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... It also allows for assessing perfusion properties, and is sometimes performed in combination with other MRI perfusion mapping techniques. It has been applied to various diseases such as inflammatory myopathies [5], joint disorders [6], dermatomyositis [7], peripheral arterial disease [8], autoimmune myositis and muscular dystrophy [9], and adolescent idiopathic scoliosis [10]. The data interpretation, however, is complicated by the dependence of IVIM parameters on the acquisition setting. ...
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Background: The purpose of this study was to investigate the dependence of Intravoxel Incoherent Motion (IVIM) parameters measured in the human calf on B0. Methods: Diffusion-weighted image data of eight healthy volunteers were acquired using five b-values (0–600 s/mm2) at rest and after muscle activation at 0.55 and 7 T. The musculus gastrocnemius mediale (GM, activated) was assessed. The perfusion fraction f and diffusion coefficient D were determined using segmented fits. The dependence on field strength was assessed using Student’s t-test for paired samples and the Wilcoxon signed-rank test. A biophysical model built on the three non-exchanging compartments of muscle, venous blood, and arterial blood was used to interpret the data using literature relaxation times. Results: The measured perfusion fraction of the GM was significantly lower at 7 T, both for the baseline measurement and after muscle activation. For 0.55 and 7 T, the mean f values were 7.59% and 3.63% at rest, and 14.03% and 6.92% after activation, respectively. The biophysical model estimations for the mean proton-density-weighted perfusion fraction were 3.37% and 6.50% for the non-activated and activated states, respectively. Conclusions: B0 may have a significant effect on the measured IVIM parameters. The blood relaxation times suggest that 7 T IVIM may be arterial-weighted whereas 0.55 T IVIM may exhibit an approximately equal weighting of arterial and venous blood.
... Suo et al. compared the ability to diagnose and assess the severity of PAD using comprehensive MRI evaluation (BOLD, ASL and IVIM) in young healthy controls, age-matched controls, and 14 patients with PAD [98]. All parameters (ASL-derived blood flow values, BOLD-derived T2* values, and IVIM-derived perfusion fraction (f) values) were correlated with transcutaneous oxygen measurements [98]. ...
... Suo et al. compared the ability to diagnose and assess the severity of PAD using comprehensive MRI evaluation (BOLD, ASL and IVIM) in young healthy controls, age-matched controls, and 14 patients with PAD [98]. All parameters (ASL-derived blood flow values, BOLD-derived T2* values, and IVIM-derived perfusion fraction (f) values) were correlated with transcutaneous oxygen measurements [98]. BOLD imaging parameters provided more robust results and significant correlation with established markers of PAD diagnosis and severity. ...
Article
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Peripheral artery disease (PAD) is a highly prevalent disorder with a high risk of mortality and amputation despite the introduction of novel medical and procedural treatments. Microvascular disease (MVD) is common among patients with PAD, and despite the established role as a predictor of amputations and mortality, MVD is not routinely assessed as part of current standard practice. Recent pre-clinical and clinical perfusion and molecular imaging studies have confirmed the important role of MVD in the pathogenesis and outcomes of PAD. The recent advancements in the imaging of the peripheral microcirculation could lead to a better understanding of the pathophysiology of PAD, and result in improved risk stratification, and our evaluation of response to therapies. In this review, we will discuss the current understanding of the anatomy and physiology of peripheral microcirculation, and the role of imaging for assessment of perfusion in PAD, and the latest advancements in molecular imaging. By highlighting the latest advancements in multi-modality imaging of the peripheral microcirculation, we aim to underscore the most promising imaging approaches and highlight potential research opportunities, with the goal of translating these approaches for improved and personalized management of PAD in the future.
... Thus, limb ischemia is associated with decreased skeletal muscle area, increased muscle fat infiltration, and decreased muscle density [17,18]; these changes can be evaluated by image features (such as CT value). Increasing evidence suggests that muscle image features can reflect tissue perfusion, assist evaluation of lower leg ischemia, and are independent predictors of cardiovascular events among people with PAD [19][20][21]. Therefore, we considered the feasibility of circumventing the assessment of vascular stenosis and analyzing CT features of the lower extremity to evaluate muscle ischemia/perfusion and conduct a quantitative auxiliary analysis of PAD severity. ...
... For muscle perfusion, several previous studies have confirmed its relationship with muscle ischemia using MR arterial spin labeling [19,37,38]. The results showed that blood flow gradually decreased with increasing severity of limb ischemia, whereas model arterial resistance progressively increased. ...
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Objectives To explore the association between lower extremity muscle features from CTA and peripheral arterial disease (PAD) severity using digital subtraction angiography (DSA) as reference standard. Methods Informed consent was waived for this Institutional Review Board approved retrospective study. PAD patients were recruited from July 2016 to September 2020. Two radiologists evaluated PAD severity on DSA and CTA using runoff score. The patients were divided into two groups: mild PAD (DSA score ≤ 7) vs. severe PAD (DSA score > 7). After segmenting lower extremity muscles from CTA, 95 features were extracted for univariable analysis, logistic regression model (LRM) analysis, and sub-dataset analysis (PAD prediction based on only part of the images). AUC of CTA score and LRMs for PAD prediction were calculated. Features were analyzed using Student’s t test and chi-squared test. p < 0.05 was considered statistically significant. Results A total of 56 patients (69 ± 11 years; 38 men) with 56 lower legs were enrolled in this study. The lower leg muscles of mild PAD group (36 patients) showed higher CT values (44.6 vs. 39.5, p < 0.001) with smaller dispersion (35.6 vs. 41.0, p < 0.001) than the severe group (20 patients). The AUC of CTA score, LRM-I (constructed with muscle features), and LRM-II (constructed with muscle features and CTA score) for PAD severity prediction were 0.81, 0.84, and 0.89, respectively. The highest predictive performance was observed in the image subset of the middle and inferior segments of lower extremity (LRM-I, 0.83; LRM-II, 0.90). Conclusions Lower extremity muscle features are associated with PAD severity and can be used for PAD prediction. Critical relevance statement Quantitative image features of lower extremity muscles are associated with the degree of lower leg arterial stenosis/occlusion and can be a beneficial supplement to the current imaging methods of vascular stenosis evaluation for the prediction of peripheral arterial disease severity. Key points • Compared with severe PAD, lower leg muscles of mild PAD showed higher CT values (39.5 vs. 44.6, p < 0.001). • Models developed with muscle CT features had AUC = 0.89 for predicting PAD. • PAD severity prediction can be realized through the middle and inferior segment of images (AUC = 0.90). Graphical Abstract
... Another study directly comparing BOLD, ASL, and intravoxel incoherent motion (IVIM) during different stages of ischemic challenge found no correlation between these MR parameters. However, several MR metrics (blood flow from ASL, T2 Ã from BOLD, and f from IVIM) correlated with noninvasive transcutaneous oxygen (tcPO 2 ) measurements (132). This highlights the unique information provided by each method. ...
... Intravoxel incoherent motion (IVIM) is a mathematical model that distinguishes the contributions of pure molecular diffusion and blood flow-related effects. Fitting to this model offers insights into both true diffusion, which reflects the microstructure of tissues, and IVIM, which reflects microcirculation within these tissues (132,(145)(146)(147). ...
... The D Ã maps that are generated can be used to evaluate changes in perfusion in PAD caused by vascular obstruction or constriction (132). It is also possible to assess changes in tissue perfusion and diffusion properties in patients with PAD by comparing DW-MRI scans taken before and after treatment (134). ...
Article
Peripheral artery disease (PAD) is a common vascular disease that primarily affects the lower limbs and is defined by the constriction or blockage of peripheral arteries and may involve microvascular dysfunction and tissue injury. Patients with diabetes have more prominent disease of microcirculation and develop peripheral neuropathy, autonomic dysfunction, and medial vascular calcification. Early and accurate diagnosis of PAD and disease characterization are essential for personalized management and therapy planning. Magnetic resonance imaging (MRI) provides excellent soft tissue contrast and multiplanar imaging capabilities and is useful as a noninvasive imaging tool in the comprehensive physiological assessment of PAD. This review provides an overview of the current state of the art of MRI in the evaluation and characterization of PAD, including an analysis of the many applicable MR imaging techniques, describing the advantages and disadvantages of each approach. We also present recent developments, future clinical applications, and future MRI directions in assessing PAD. The development of new MR imaging technologies and applications in pre-clinical models with translation to clinical research holds considerable potential for improving the understanding of the pathophysiology of PAD and clinical applications for improving diagnostic precision, risk stratification, and treatment outcomes in patients with PAD.
... To our knowledge, perfusion in feet has not previously been quantified with PET, and only a few studies using MRI or CT have been published. Arterial spin labeling MRI appears to yield perfusion approximately 10 times higher than the current study in both lower legs and feet [20][21][22], whereas a small dynamic CT study in patients with diabetic foot found perfusion values more in line with the current study (0.5-0.7 mL/ min/100 mL in healthy tissue of the feet) [23]. In both lower legs and feet, the interindividual variation was larger than the intraindividual variation in muscle perfusion (coefficient of variation 37% vs. 29% and 71% vs. 40%, respectively). ...
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Background [¹⁵O]H2O PET/CT allows noninvasive quantification of tissue perfusion and can potentially play a future role in the diagnosis and treatment of peripheral artery disease. We aimed to evaluate the reliability of dynamic [¹⁵O]H2O PET imaging for measuring lower extremity skeletal muscle perfusion. Ten healthy participants underwent same-day test–retest study with six dynamic [¹⁵O]H2O PET scans of lower legs and feet. Manual volume-of-interests were drawn in skeletal muscles, and PET time activity curves were extracted. K1 values (mL/min/100 mL) were estimated using a single-tissue compartment model (1TCM), autoradiography (ARG), and parametric imaging with blood input functions obtained from separate heart scans. Results Resting perfusion values in the muscle groups of the lower legs ranged from 1.18 to 5.38 mL/min/100 mL (ARG method). In the muscle groups of the feet, perfusion values ranged from 0.41 to 3.41 mL/min/100 mL (ARG method). Test–retest scans demonstrated a strong correlation and good repeatability for skeletal muscle perfusion with an intraclass correlation coefficient (ICC) of 0.88 and 0.87 and a repeatability coefficient of 34% and 53% for lower legs and feet, respectively. An excellent correlation was demonstrated when comparing volume-of-interest-based methods (1TCM and ARG) (lower legs: ICC = 0.96, feet: ICC = 0.99). Parametric images were in excellent agreement with the volume-of-interest-based ARG method (lower legs: ICC = 0.97, feet: ICC = 0.98). Conclusion Parametric images and volume-of-interest-based methods demonstrated comparable resting perfusion values in the lower legs and feet of healthy individuals. The largest variation was seen between individuals, whereas a smaller variation was seen between muscle groups. Repeated measurements of resting blood flow yielded a strong overall correlation for all methods.
... In addition, BOLD is usually used to assess muscle perfusion after a given stimulation, such as cuff compression (20). BOLD may be a more reliable technique for evaluating lower limb muscle perfusion in patients with peripheral arterial disease at rest and may provide additional information about skeletal muscle perfusion (21). ...
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Background: Patients with chronic low back pain (CLBP) undergo structural changes of the paraspinal muscles; however, it is unclear if functional changes also occur. This study aimed to examine the metabolic and perfusion function changes in the paraspinal muscles of patients with CLBP as indirectly reflected by blood oxygen level-dependent (BOLD) imaging and T2 mapping. Methods: All participants were consecutively enrolled at our local hospital from December 2019 to November 2020. Patients were diagnosed with CLBP in the outpatient clinic, and asymptomatic participants were considered to be those with no CLBP or other diseases. This study was not registered on a clinical trial platform. Participants underwent BOLD imaging and T2 mapping scans at the L4-S1 disc level. The effective transverse relaxation rate (R2* values) and transverse relaxation time (T2 values) of the paraspinal muscles were measured on the central plane of the L4/5 and L5/S1 intervertebral discs. Finally, the independent samples t-test was used to assess the differences in R2* and T2 values between the 2 groups, while Pearson correlation analysis was used to determine their correlation with age. Results: A total of 60 patients with CLBP and 20 asymptomatic participants were enrolled. The paraspinal muscles of the CLBP group had higher total R2* values [46.7±2.9 vs. 44.0±2.9 s-1; 95% confidence interval (CI): 1.2-4.2; P=0.001] and lower total T2 values (45.4±4.2 vs. 47.1±3.7 ms; 95% CI: -3.8 to 0.4; P=0.109) than did the asymptomatic participants. For the different muscles, R2* values for the erector spinae (ES) (L4/5: 45.5±2.6 vs. 43.0±3.0 s-1, 95% CI: 1.1-4.0, P=0.001; L5/S1: 48.5±4.9 vs. 45.9±4.2 s-1; 95% CI: 0.2-5.1; P=0.035) and the R2* values of the multifidus (MF) muscles (L4/5: 46.4±2.9 vs. 43.7±3.5 s-1, 95% CI: 1.1-4.3, P=0.001; L5/S1: 46.3±3.5 vs. 42.5±2.8 s-1, 95% CI: 2.1-5.5, P<0.001) of the CLBP group at both spinal levels were higher than those of the asymptomatic participants. In the patients with CLBP, the R2* values at the L4/5 (45.9±2.1 s-1) were lower than those at the L5/S1 (47.4±3.6 s-1; 95% CI: -2.6 to -0.4; P=0.007). The R2* values were positively correlated with age in both groups (CLBP group: r=0.501, 95% CI: 0.271-0.694, P<0.001; asymptomatic group: r=0.499, 95% CI: -0.047 to 0.771; P=0.025). Conclusions: The R2* values were higher in the paraspinal muscles of patients with CLPB and may suggest metabolic and perfusion dysfunction of the paraspinal muscles in these patients.
... Several non-invasive techniques have been introduced to measure tissue perfusion in the lower extremities. These techniques include hyperspectral imaging (HSI) [34], laser doppler perfusion monitoring (LDPM) [15,25], laser speckle contrast imaging (LSCI) [25,34], near-infrared spectroscopy (NIRS) [2,25], spectrophotometry [3,25], transcutaneous oxygenation measurements (TCOM) [3] and vascular optical tomography imaging [20]. TcPO 2 is a gold-standard approach that is used to quantify skin oxygenation. ...
... Several non-invasive techniques have been introduced to measure tissue perfusion in the lower extremities. These techniques include hyperspectral imaging (HSI) [34], laser doppler perfusion monitoring (LDPM) [15,25], laser speckle contrast imaging (LSCI) [25,34], near-infrared spectroscopy (NIRS) [2,25], spectrophotometry [3,25], transcutaneous oxygenation measurements (TCOM) [3] and vascular optical tomography imaging [20]. TcPO 2 is a gold-standard approach that is used to quantify skin oxygenation. ...
Article
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Near-infrared spectroscopy (NIRS)-based peripheral perfusion, or microcirculation, can be used to assess the severity of peripheral vascular dysfunction. A low-cost, portable non-contact near-infrared optical scanner (NIROS) was developed for spatio-temporal mapping of tissue oxygenation and perfusion in tissues. In vivo validation studies were carried out on control subjects (n = 3) to assess the ability of NIROS to measure real-time oxygenation changes in response to an occlusion paradigm on the dorsum of the hand. NIROS captured real-time tissue oxygenation changes with 95% correlation when compared to a commercial device. A feasibility peripheral imaging study was performed in a mouse model (n = 5) of chronic kidney disease (CKD) induced vascular calcification to assess differences in microcirculatory peripheral tissue oxygenation. The tissue oxygenation (in terms of oxy-, deoxy-, and total hemoglobin changes) due to the occlusion paradigm was distinctly different prior to (week-6) and after the onset of vascular calcification (week-12) in the murine tails. Future work will involve extensive studies to correlate these microcirculatory tissue oxygenation changes in the peripheral tail to the vascular calcification in the heart.
... This has been applied to skeletal muscle in the extremities and, more recently, to the diabetic foot. [18][19][20][21] The objective of this study is to investigate the novel application of ASL to assess foot perfusion in both healthy volunteers without wounds and diabetic volunteers with foot ulcers. This pilot study aims to quantify peri-wound foot perfusion at various tissue depths and compare this with foot perfusion in healthy volunteers. ...
Article
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Objective Tools that quantify tissue perfusion of the foot are deficient, contributing to the uncertainty in predicting ulcer healing potential. This pilot study aims to quantify peri-wound foot perfusion at various tissue depths using a novel application of pseudo-continuous arterial spin labeling magnetic resonance imaging. Methods Ten diabetic patients with neuropathic wounds and 20 healthy volunteers without wounds were recruited. Wounds were graded according to the Wound, Ischemia, Foot Infection (WIfI) system. All subjects underwent a noncontrasted ASL MRI of the foot for perfusion measurements. For healthy volunteers, perfusion was compared at rest and during sustained toe flexion between four regions: lateral plantar, medial plantar, lateral calcaneal, and medial calcaneal. Evaluations of diabetic volunteers compared perfusion between four zones: wound, near border, far border, and remote. Remote zone perfusion in diabetics was compared with perfusion in the plantar foot of healthy volunteers. Results There were 11 wounds, which were located over the metatarsal heads in five, the stump of a transmetatarsal amputation in three, the heel in two, and the mid foot in one. The median WIfI stage was 2. One patient had a WIfI ischemia grade of 1; the remaining patients’ grades were 0. The mean ankle-brachial index was 1.0 ± 0.3. There were two patients with a WIfI foot infection grade of 1; the remaining patients’ grades were 0. In healthy volunteers, plantar foot perfusion with sustained toe flexion was 43.9 ± 1.7 mL/100g/min and significantly higher than perfusion at rest (27.3 ± 2.7 mL/100g/min; P < .001). In diabetic patients, perfusion at the wound, near border, far border, and remote regions was 96.1 ± 10.7, 92.7 ± 9.4, 73.4 ± 8.2, and 62.8 ± 2.7 mL/100g/min. Although this perfusion pattern persisted throughout the depth of the wound, perfusion decreased with tissue depth. In the near border, perfusion at 20% of the wound depth was 124.0 ± 35.6 mL/100g/min and 69.9 ± 10.1 mL/100g/min at 100% (P = .006). Lastly, remote perfusion in diabetics was 2.3 times the plantar perfusion in healthy volunteers (27.3 ± 2.7 mL/100g/min; P < .001). Conclusions The pattern of resting tissue perfusion around nonischemic diabetic foot ulcers was successfully quantified with arterial spin labeling magnetic resonance imaging. Diabetic patients with wounds were hyperemic compared with healthy volunteers. There was a 1.5-fold increase in peri-wound tissue perfusion relative to the rest of the foot. This study is the first step in developing a tool to assess the perfusion deficit in ischemic wounds.
... A lot of new blood perfusion in tissues evaluating techniques have emerged recently, trying to prove their value: contrast-enhanced ultrasound [16][17][18]; MRI perfusion imaging [19][20][21]; hyperspectral imaging [22,23]; laser doppler perfusion monitoring [12]; laser speckle contrast imaging [24,25]; near-infrared spectroscopy [26][27][28][29]; near-infrared fluorescence imaging with indocyanine green [30,31]; spectrophotometry [32]; vascular optical tomography imaging [33]; photoacoustic imaging; micro-oxygen sensors [34] and some other emerging techniques. However scientific data is scarce and only two of the studies mentioned above have included more than 100 patients. ...
Article
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Objectives: Current methods evaluating tissue ischemia are based mainly on evaluating blood flow and not tissue perfusion. However, diabetes mainly affects small vessels and blood flow evaluation is insufficient. The aim of the trial was to evaluate the feasibility of NIRS in measuring perfusion changes during chronic total occlusion (CTO) revascularization in below the knee (BTK) arteries. Methods and Material: A prospective observational study was performed. During the endovascular revascularization procedure, tissue oxygenation changes were measured using three NIRS sensors. Postoperative angiographies and 30 days wound healing was evaluated. Results: The study enrolled 30 patients with chronic limb threatening ischemia, occluded below the knee arteries, Rutherford 5. Mean age 74.7 ± 11.2 years, 16 (53%) of the patients had diabetes mellitus, 10 (33%) had end-stage renal disease. A statistically significant NIRS rSO2 increase was observed on sensors near the wound after the revascularization, p = 0.001. Thirty days follow-up visits included 27 patients, because 3 patients had died. Comparing good wound healing group with poor wound healing group intraoperative NIRS rSO2 increase difference was statistically significant, p = 0.017. Conclusions: The study confirmed tissue perfusion increase could be detected using NIRS during revascularization of below the knee arteries. An intraoperative increase of NIRS rSO2 proved to predict wound healing results.
... Moreover, significant correlation between T2* and ABI values was observed in PAD patients. 50 Advantages/Disadvantages MR perfusion techniques can be used for evaluation of microcirculation and estimation of revascularization outcome in patients with PAD. These examinations can be performed without radiation and the majority of them (BOLD, ASL, IVIM) without necessity of contrast agents. ...
Article
Lower limb peripheral arterial disease (PAD) characterizes the impairment of blood flow to extremities caused by arterial stenoses or occlusions. Evaluation of PAD is based on clinical examination, calculation of ankle-brachial index and imaging studies such as ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and digital subtraction angiography (DSA). These modalities provide significant information about location, extension and severity of macrovasular lesions in lower extremity arterial system. However, they can be also used to evaluate limb perfusion, using appropriate techniques and protocols. This information may be valuable for assessment of the severity of ischemia and detection of hypoperfused areas. Moreover, they can be used for planning of revascularization strategy in patients with severe PAD and evaluation of therapeutic outcome. These techniques may also determine prognosis and amputation risk in patients with PAD. This review gives a basic overview of the perfusion techniques for lower limbs provided by imaging modalities such as US, CT, MRI, DSA and scintigraphy and their clinical applications for evaluation of PAD and revascularization outcome.