Assessing the end-organ in peripheral arterial occlusive disease-from contrast-enhanced ultrasound to blood-oxygen-level-dependent MR imaging.

Peripheral arterial occlusive disease (PAOD) is a result of atherosclerotic disease which is currently the leading cause of morbidity and mortality in the western world. Patients with PAOD may present with intermittent claudication or symptoms related to critical limb ischemia. PAOD is associated with increased mortality rates. Stenoses and occlusions are usually detected by macrovascular imaging, including ultrasound and cross-sectional methods. From a pathophysiological view these stenoses and occlusions are affecting the microperfusion in the functional end-organs, such as the skin and skeletal muscle. In the clinical arena new imaging technologies enable the evaluation of the microvasculature. Two technologies currently under investigation for this purpose on the end-organ level in PAOD patients are contrast-enhanced ultrasound (CEUS) and blood-oxygen-level-dependent (BOLD) MR imaging (MRI). The following article is providing an overview about these evolving techniques with a specific focus on skeletal muscle microvasculature imaging in PAOD patients.

Correlation of skeletal muscle blood oxygenation level-dependent MRI and skin laser Doppler flowmetry in patients with systemic sclerosis.

PURPOSE: To investigate the origin of skeletal muscle BOLD MRI alterations in patients with systemic sclerosis (SSc) by correlating BOLD MRI T2* signal of calf muscles with microcirculatory blood flow of calf skin measured by laser Doppler flowmetry (LDF). MATERIALS AND METHODS: BOLD MRI (3T) and LDF measurements were performed in 12 consecutive SSc patients (6 women, 6 men; mean age 54.0 ± 10.0 years) and 12 healthy volunteers (4 men, 8 women; mean age 44.7 ± 13.1 years). For both modalities, the same cuff compression paradigm at mid-thigh level was used. LDF datasets were acquired using a PeriScan PIM II Imager (Perimed AB, Stockholm, Sweden) at the upper calf corresponding to the level of MR imaging. Cross-correlations of BOLD and LDF signal intensity changes depending on time lags between both time series were calculated. RESULTS: Maximal cross-correlations of BOLD T2* and LDF measurements were calculated as 0.93 (healthy volunteers) and 0.94 (SSc patients) for a BOLD time lag of approximately 10 s. Key parameter analysis suggested that in contrast to hyperemic BOLD signal loss at maximum value in SSc patients, ischemic T2* decrease cannot be explained by differences of tissue perfusion. CONCLUSION: Skeletal muscle BOLD T2* signal in SSc patients is closely correlated with changes of microperfusion as detected by LDF.

Correlation of muscle BOLD MRI with transcutaneous oxygen pressure for assessing microcirculation in patients with systemic sclerosis.

PURPOSE: To prospectively compare calf muscle BOLD MRI with transcutaneous oxygen pressure (TcPO2 ) measurement in patients with systemic sclerosis (SSc) and healthy volunteers and thereby get insight into the pathogenesis of vasculopathy in this connective tissue disorder. MATERIALS AND METHODS: Twelve patients with SSc (6 women and 6 men, mean age 53.5 ± 10.0 years) and 12 healthy volunteers (4 men and 8 women, mean age 47 ± 12.1 years) were examined using muscle BOLD MRI and TcPO2. A cuff compression at mid-thigh level was performed to provoke ischemia and reactive hyperemia. BOLD measurements were acquired on a 3 Tesla whole body-scanner in the upper calf region using a multi-echo EPI-sequence with four echo-times (TE: 9/20/31/42 ms) and a repetition time of 2 s. Empirical cross-correlation analysis depending on time lags between BOLD- and TcPO2-measurements was performed. RESULTS: Maximal cross-correlation of BOLD T2*- and TcPO2-measurements was calculated as 0.93 (healthy volunteers) and 0.90 (SSc patients) for a time lag of approximately 40 s. Both modalities showed substantial differences regarding time course parameters between the SSc patients and healthy volunteers. CONCLUSION: Skeletal muscle BOLD MRI correlated very well with TcPO2 . T2* changes seem to reflect reoxygenation deficits in deeper muscle tissue of SSc patients.

Skeletal muscle BOLD MRI: from underlying physiological concepts to its usefulness in clinical conditions.

Blood oxygenation-level dependent (BOLD) MRI has gained particular attention in functional brain imaging studies, where it can be used to localize areas of brain activation with high temporal resolution. To a higher degree than in the brain, skeletal muscles show extensive but transient alterations of blood flow between resting and activation state. Thus, there has been interest in the application of the BOLD effect in studying the physiology of skeletal muscles (healthy and diseased) and its possible application to clinical practice. This review outlines the potential of skeletal muscle BOLD MRI as a diagnostic tool for the evaluation of physiological and pathological alterations in the peripheral limb perfusion, such as in peripheral arterial occlusive disease. Moreover, current knowledge is summarized regarding the complex mechanisms eliciting BOLD effect in skeletal muscle. We describe technical fundaments of the procedure that should be taken into account when performing skeletal muscle BOLD MRI, including the most often applied paradigms to provoke BOLD signal changes and key parameters of the resulting time courses. Possible confounding effects in muscle BOLD imaging studies, like age, muscle fiber type, training state, and drug effects are also reviewed in detail.

Clinical implications of skeletal muscle blood-oxygenation-level-dependent (BOLD) MRI.

Blood-oxygenation-level-dependent (BOLD) contrast in magnetic resonance (MR) imaging of skeletal muscle mainly depends on changes of oxygen saturation in the microcirculation. In recent years, an increasing number of studies have evaluated the clinical relevance of skeletal muscle BOLD MR imaging in vascular diseases, such as peripheral arterial occlusive disease, diabetes mellitus, and chronic compartment syndrome. BOLD imaging combines the advantages of MR imaging, i.e., high spatial resolution, no exposure to ionizing radiation, with functional information of local microvascular perfusion. Due to intrinsic contrast provoked via changes in hemoglobin oxygen saturation, it is a safe and easy applicable procedure on standard whole-body MR devices. Therefore, BOLD MR imaging of skeletal muscle is a potential new diagnostic tool in the clinical evaluation of vascular, inflammatory, and muscular pathologies. Our review focuses on the current evidence concerning the use of BOLD MR imaging of skeletal muscle under pathological conditions and highlights ways for future clinical and scientific applications.

Blood oxygenation level-dependent (BOLD) MRI of human skeletal muscle at 1.5 and 3 T.

PURPOSE: To evaluate the dependence of skeletal muscle blood oxygenation level-dependent (BOLD) effect and time course characteristics on magnetic field strength in healthy volunteers using an ischemia/reactive hyperemia paradigm. MATERIALS AND METHODS: Two consecutive skeletal muscle BOLD magnetic resonance imaging (MRI) measurements in eight healthy volunteers were performed on 1.5 T and 3.0 T whole-body MRI scanners. For both measurements a fat-saturated multi-shot multiecho gradient-echo EPI sequence was applied. Temporary vascular occlusion was induced by suprasystolic cuff compression of the thigh. T2 time courses were obtained from two different calf muscles and characterized by typical curve parameters. Ischemia- and hyperemia-induced changes in R2 (ΔR2) were calculated for both muscles in each volunteer at the two field strengths. RESULTS: Skeletal muscle BOLD changes are dependent on magnetic field strength as the ratio ΔR2(3.0 T)/ΔR2(1.5 T) was found to range between 1.6 and 2.2. Regarding time course characteristics, significantly higher relative T2 changes were found in both muscles at 3.0 T. CONCLUSION: The present study shows an approximately linear field strength dependence of ΔR2 in the skeletal muscle in response to ischemia and reactive hyperemia. Using higher magnetic fields is advisable for future BOLD imaging studies of peripheral limb pathologies.