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Data from gastrocnemius (fast-twitch) and soleus (slow-twitch) muscle before and immediately following strenuous exercise. Hyperoxia was applied as the stimulus for BOLD signal modulation. The BOLD contrast was greater in the soleus at rest. In addition, the application of exercise resulted in greatest BOLD contrast in the soleus, as assessed through number of significantly changed pixels and the area under the impulse response function.
Source publication
Blood-oxygen-level-dependent (BOLD) imaging was a concept introduced in 1990 for evaluating brain activation. The method relies on magnetic resonance imaging (MRI) contrast resulting from changes in the microvascular ratio of oxyhaemoglobin (oxyHb) to deoxyhaemoglobin (deoxyHb). OxyHb is diamagnetic, whereas deoxyHb is paramagnetic, which produces...
Contexts in source publication
Context 1
... caused by dissolved O 2 (which under optimal conditions could reach up to 400 mm Hg). On the venous side, during hyperoxia exposure, the deoxyHb levels are higher as the dissolved O 2 preferentially leaves the microcirculation, sparing the oxyHb. The result is an increase in T 2 . It is now well known that absolute differences in T 2 or T 2 * can be demonstrated in muscle. However, of greater interest is rapid assessment of percentage changes in T 2 * with hyperoxia. Such studies, called O 2 -enhanced MRI, are theorized to give information on the local microvasculature through changes in BOLD signal. Oxygen-enhanced MR has been performed on the brain, 57 heart, 58 and various skeletal muscles. 59 As muscle fiber types (slow- or fast-twitch) have different vascular densities, they should have different hemodynamic responses, which should then be detectable with oxygen- enhanced MR. The gastrocnemius, a fast-twitch type IIB muscle, relies on glycolytic anaerobic metabolism. It is easily fatigued and has comparatively few capillaries and myoglobin protein relative to slow-twitch muscles such as the soleus. The soleus muscle employs oxidative metabolism, andhence requires a greater number of capillaries and myoglobin for O 2 delivery. As such, the soleus does not fatigue as quickly as the gastrocnemius. Because of the inherent differences in microvascular density between slow- and fast-twitch muscle, the resultant differences in blood volume and perfusion should manifest in differing BOLD signals during oxygen-enhanced MR. Using hyperoxia (100% O 2 ) as a BOLD contrast agent, we have made preliminary observations on the lower leg (soleus and gastrocnemeus muscles) in an attempt to quantify differences between rest and fatigued states. Healthy males with an average age of 20 year (range 18–21) were screened and approved for imaging using a General Electric (GE, Milwaukee, WI) 1.5-Tesla CV/i MRI with maximum gradient strength of 4 g/cm. The right calf was immobilized in a transmit-receive ex- tremity coil padded to minimize movement during data acquisition. Care was given to not restrict blood flow (i.e., no compressive padding to the posterior surface of the knee). The subject’s position in the coil was marked on their bare skin to allow accurate pre- and postexercise alignment. The oxygen treatment consisted of a “boxcar paradigm” in which normoxic (room air) phases of 1.5 minutes were cycled with hyperoxic states (100% oxygen at 22 L/min) lasting 45 seconds. At this level of O 2 exposure, Losert et al 57 , using a pulsed oximeter, showed O 2 saturation occurred after 70 seconds, with the level returning to basal levels following 150 seconds of normoxic breathing. Hence in our current work we have dou- bled the normoxia phase. A mask with a Laerdal bag, an oxygen reservoir, and a one-way valve was essential for maximizing oxygen delivery to the calf and thus allow- ing a significant T 2 signal change. 21 The BOLD scan lasted a total of 9 minutes and consisted of four cycles of normoxia and hyperoxia, after which subjects were removed from the MRI and pro- ceeded to perform 200 one-legged (right) calf-raises, lasting a total of ~2.5 minutes. Subsequently the subject was rescanned in the same location, with the same scan- ner calibration settings and using the same “boxcar paradigm” as for the preexercise scan. Functional images were acquired using a spiral- based readout. Spiral k-space acquisition is less sensitive to magnetic susceptibility and field inhomogeneity, arti- facts—particularly Nyquist ghosting—and motion compared with rectilinear k-space acquisition schemes such as echo-planar imaging. 60 Functional images were acquired with the following parameters: one slice, 20-cm field of view, 5 mm thick, TE/TR = 40 ms/1.5 s 2 NEX, 100 kHz bandwidth, one spiral interleaf (4096 points). Before Fourier transformation, spiral k-space data was regridded to Cartesian based coordinates giving a final voxel size of 3.75 ϫ 3.75 ϫ 5 mm thick. Datasets were processed with AFNI (MCW Wisconsin), much the same as fMRI analysis for functional brain imaging. 61 Briefly, deconvolution of the hemodynamic impulse response function (IRF) and the ideal (“boxcar paradigm”) waveform was performed with a minimum stimulus lag of 3 seconds (2 TR) and a maximum lag of 15 seconds (10 TRs) to allow time for O 2 delivery to the muscle. The area under the IRF curve was summed and a Gaussian blur (fwhm = 3 voxels) was performed to increase the probability of activation. Re- gions of interest (ROIs) were drawn over the gastrocnemius and soleus muscles, and the number of activated voxels, average intensity, and area under the IRF curve for all ROIs were calculated. In this preliminary study a significant increase in the area under the IRF curve ( P < .0055) and mean signal intensity ( P < .0013) were observed after exercise (Fig. 2). Following exercise, the area under the IRF curve increased more in the soleus than in the gastrocnemius (Fig. 2). A greater increase in mean signal intensity postexercise was observed in the gastrocnemius, with mini- mal change observed in the soleus. The limited vasculature in the gastrocnemius likely as a limited effect on VO 2 during exercise 62 and would slow the removal of deoxyHb in the tissue. The soleus has a greater microvascular density than the gastrocnemius and reacts almost instantly to change in oxygen. 63 This explains the relatively inert response to exercise on mean intensity: The blood is quickly re- oxygenated. However, the vasculature most likely dilated in response to exercise. 64 This is implied by the increase in BOLD MR signal 65 , resulting in a greater IRF curve area for the soleus. Our preliminary study, evaluating the response of slow- and fast-twitch muscles in human calves, could be ben- eficial in the understanding of muscle vascular response to stimuli (e.g., exercise) in diseases such as muscular dystrophy, ischemia, and chronic/peripheral venous insufficiency. Fiber-specific BOLD imaging of muscle may possibly be used to determine what percentage of muscle fibers are present in different types of athletes. For example, rats with genetically enhanced muscles (for more type II fibers) demonstrated more power. Sprinters should exemplify a large increase in signal intensity and not in area. Also in chronic/peripheral venous insufficiency, venous hypertension occurs as a result of structural or functional abnormalities of veins, which could be detected by BOLD imaging of different muscle. Furthermore, muscles can rapidly change in size and haemodynamics based on use, 13 so changes in BOLD signal and muscle fiber types could indicate an ulcer that has changed one’s gait, an injury, or even neurological complications such as spinal lesions and Parkinson’s, which can lead to a shortening of motor units and unnatural muscle contracture. In the calf, stretching of tonically activated muscles can inter- fere with the regular gait (controlled by gastrocnemius or soleus EMG activity). As a result, muscle tension ef- ficiency is jeopardized. 13 Last, muscle fiber composition, which could be enhanced by certain exercise regimes to favor slow- or fast-twitch fibers, may possibly be assessed using BOLD imaging ...
Context 2
... appreciably, as haemoglobin (Hb) is already 98% saturated with O 2 . The resultant T 2 changes are ex- clusively caused by dissolved O 2 (which under optimal conditions could reach up to 400 mm Hg). On the venous side, during hyperoxia exposure, the deoxyHb levels are higher as the dissolved O 2 preferentially leaves the microcirculation, sparing the oxyHb. The result is an increase in T 2 . It is now well known that absolute differences in T 2 or T 2 * can be demonstrated in muscle. However, of greater interest is rapid assessment of percentage changes in T 2 * with hyperoxia. Such studies, called O 2 -enhanced MRI, are theorized to give information on the local microvasculature through changes in BOLD signal. Oxygen-enhanced MR has been performed on the brain, 57 heart, 58 and various skeletal muscles. 59 As muscle fiber types (slow- or fast-twitch) have different vascular densities, they should have different hemodynamic responses, which should then be detectable with oxygen- enhanced MR. The gastrocnemius, a fast-twitch type IIB muscle, relies on glycolytic anaerobic metabolism. It is easily fatigued and has comparatively few capillaries and myoglobin protein relative to slow-twitch muscles such as the soleus. The soleus muscle employs oxidative metabolism, andhence requires a greater number of capillaries and myoglobin for O 2 delivery. As such, the soleus does not fatigue as quickly as the gastrocnemius. Because of the inherent differences in microvascular density between slow- and fast-twitch muscle, the resultant differences in blood volume and perfusion should manifest in differing BOLD signals during oxygen-enhanced MR. Using hyperoxia (100% O 2 ) as a BOLD contrast agent, we have made preliminary observations on the lower leg (soleus and gastrocnemeus muscles) in an attempt to quantify differences between rest and fatigued states. Healthy males with an average age of 20 year (range 18–21) were screened and approved for imaging using a General Electric (GE, Milwaukee, WI) 1.5-Tesla CV/i MRI with maximum gradient strength of 4 g/cm. The right calf was immobilized in a transmit-receive ex- tremity coil padded to minimize movement during data acquisition. Care was given to not restrict blood flow (i.e., no compressive padding to the posterior surface of the knee). The subject’s position in the coil was marked on their bare skin to allow accurate pre- and postexercise alignment. The oxygen treatment consisted of a “boxcar paradigm” in which normoxic (room air) phases of 1.5 minutes were cycled with hyperoxic states (100% oxygen at 22 L/min) lasting 45 seconds. At this level of O 2 exposure, Losert et al 57 , using a pulsed oximeter, showed O 2 saturation occurred after 70 seconds, with the level returning to basal levels following 150 seconds of normoxic breathing. Hence in our current work we have dou- bled the normoxia phase. A mask with a Laerdal bag, an oxygen reservoir, and a one-way valve was essential for maximizing oxygen delivery to the calf and thus allow- ing a significant T 2 signal change. 21 The BOLD scan lasted a total of 9 minutes and consisted of four cycles of normoxia and hyperoxia, after which subjects were removed from the MRI and pro- ceeded to perform 200 one-legged (right) calf-raises, lasting a total of ~2.5 minutes. Subsequently the subject was rescanned in the same location, with the same scan- ner calibration settings and using the same “boxcar paradigm” as for the preexercise scan. Functional images were acquired using a spiral- based readout. Spiral k-space acquisition is less sensitive to magnetic susceptibility and field inhomogeneity, arti- facts—particularly Nyquist ghosting—and motion compared with rectilinear k-space acquisition schemes such as echo-planar imaging. 60 Functional images were acquired with the following parameters: one slice, 20-cm field of view, 5 mm thick, TE/TR = 40 ms/1.5 s 2 NEX, 100 kHz bandwidth, one spiral interleaf (4096 points). Before Fourier transformation, spiral k-space data was regridded to Cartesian based coordinates giving a final voxel size of 3.75 ϫ 3.75 ϫ 5 mm thick. Datasets were processed with AFNI (MCW Wisconsin), much the same as fMRI analysis for functional brain imaging. 61 Briefly, deconvolution of the hemodynamic impulse response function (IRF) and the ideal (“boxcar paradigm”) waveform was performed with a minimum stimulus lag of 3 seconds (2 TR) and a maximum lag of 15 seconds (10 TRs) to allow time for O 2 delivery to the muscle. The area under the IRF curve was summed and a Gaussian blur (fwhm = 3 voxels) was performed to increase the probability of activation. Re- gions of interest (ROIs) were drawn over the gastrocnemius and soleus muscles, and the number of activated voxels, average intensity, and area under the IRF curve for all ROIs were calculated. In this preliminary study a significant increase in the area under the IRF curve ( P < .0055) and mean signal intensity ( P < .0013) were observed after exercise (Fig. 2). Following exercise, the area under the IRF curve increased more in the soleus than in the gastrocnemius (Fig. 2). A greater increase in mean signal intensity postexercise was observed in the gastrocnemius, with mini- mal change observed in the soleus. The limited vasculature in the gastrocnemius likely as a limited effect on VO 2 during exercise 62 and would slow the removal of deoxyHb in the tissue. The soleus has a greater microvascular density than the gastrocnemius and reacts almost instantly to change in oxygen. 63 This explains the relatively inert response to exercise on mean intensity: The blood is quickly re- oxygenated. However, the vasculature most likely dilated in response to exercise. 64 This is implied by the increase in BOLD MR signal 65 , resulting in a greater IRF curve area for the soleus. Our preliminary study, evaluating the response of slow- and fast-twitch muscles in human calves, could be ben- eficial in the understanding of muscle vascular response to stimuli (e.g., exercise) in diseases such as muscular dystrophy, ischemia, and chronic/peripheral venous insufficiency. Fiber-specific BOLD imaging of muscle may possibly be used to determine what percentage of muscle fibers are present in different types of athletes. For example, rats with genetically enhanced muscles (for more type II fibers) demonstrated more power. Sprinters should exemplify a large increase in signal intensity and not in area. Also in chronic/peripheral venous insufficiency, venous hypertension occurs as a result of structural or functional abnormalities of veins, which could be detected by BOLD imaging of different muscle. Furthermore, muscles can rapidly change in size and haemodynamics based on use, 13 so changes in BOLD signal and muscle fiber types could indicate an ulcer that has changed one’s gait, an injury, or even neurological complications such as spinal lesions and Parkinson’s, which can lead to a shortening of motor units and unnatural muscle contracture. In the calf, stretching of tonically activated muscles can inter- fere with the regular gait (controlled by gastrocnemius or soleus EMG activity). As a result, muscle tension ef- ficiency is jeopardized. 13 Last, muscle fiber composition, which could be enhanced by certain exercise regimes to favor slow- or fast-twitch fibers, may possibly be assessed using BOLD imaging ...
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Citations
... Blood oxygen level-dependent (BOLD) contrast primarily comes from the microvascular ratio of oxyhemoglobin to deoxyhemoglobin as they have distinct magnetic properties that cause a susceptibility effect (108,109). Deoxygenated blood contributes to shorter T2 Ã , i.e., faster signal decay, in water. Thus, an influx of oxygenated blood lengthens T2 Ã , acting as an internal contrast agent that manifests itself as a slight brightening of the water signal at fixed echo time. ...
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.
... With regard to the T2 � relaxation time, it is assumed that vasodilatation, as a primary response of the muscle to exercise, is initially accompanied by a a consecutively reduced oxygen extraction rate and thus a decrease in paramagnetic deoxyhemoglobin and an increase in diamagnetic oxyhemoglobin respectively [29]. While the paramagnetic deoxyhaemoglobin shortens the T2 � relaxation time of the water protons, the diamagnetic oxyhaemoglobin does not influence the signal intensity of the water protons, resulting in an overall increase in the T2 � relaxation time [30][31][32], hence presumably reflecting BOLD effects in the tissue [33][34][35]. The subsequent plateau phase and the following decrease in relaxation time could thus represent a short-term equilibrium between vasodilatation and oxygen extraction rate, and a consecutive decrease in T2 � relaxation time due to a further increase in deoxyhemoglobin with continued exercise. ...
Objectives
Previous studies on T2* and T2 relaxation time of the muscles have shown that exercise leads to an initial increase, presumably representing different intramuscular physiological processes such as increase in intracellular volume or blood oxygenation level dependent effects with a subsequent decrease after cessation of exercise. Their behaviour during prolonged exercise is still unknown but could provide important information for example about the pathophysiology of overuse injuries. The aim of this study was to evaluate the temporal course of T2* and T2 relaxation time in extrinsic foot muscles during prolonged exercise and determine the optimal mapping technique.
Methods
Ten participants had to run a total of 75 minutes at their individual highest possible running speed, with interleaved MR scans at baseline and after 2.5, 5, 10, 15, 45 and 75 minutes. The examined extrinsic foot muscles were manually segmented, and relaxation time were analysed regarding its respective time course.
Results
T2* and T2 relaxation time showed an initial increase, followed by a plateau phase between 2.5 and 15 minutes and a subsequent decrease. For the T2* relaxation time, this pattern was also apparent, but less pronounced, with more muscles not reaching significance (p<0.05) when comparing different time points.
Conclusions
T2* and T2 relaxation time showed a similar course with an initial rapid increase, a plateau phase and a subsequent decrease under prolonged exercise. Moderate but long-term muscular activity appears to have a weaker effect on T2* relaxation time than on T2 relaxation time.
... It is also important to keep in mind that the oxygenation level of intravascular hemoglobin is not only dependent from oxyhemoglobin supply and deoxygenation rate of the respective tissue, but it is also sensitive to changes in perfusion, cellular pH, vessel diameter, and vessel orientation (54)(55)(56)(57)(58)(59), considering the origin of BOLD-MRI signal as multifactorial. However, it has been postulated that the BOLD signal changes primarily result from changes in the concentration of deoxyhemoglobin in muscle microcirculation (60). ...
... In the past, BOLD-MRI was used to assess brain activation (52), but now it can also provide information regarding activation and oxygenation of many other tissues including the kidneys (70) and skeletal muscles (54,60,68), as already done by Ledermann et al. and Potthast et al. that demonstrated the value of BOLD-MRI of skeletal muscle in assessment of microvascular function in patient with PAD (71,72). Moreover, BOLD-MRI has also been used to evaluate the efficacy of PTA of superficial femoral artery in patients with symptomatic stenosis (73), underlying its potential usefulness in evaluation of treatment approaches, as endovascular revascularization. ...
Diabetes mellitus (DM) is one of the most common metabolic diseases worldwide; its global burden has increased rapidly over the past decade, enough to be considered a public health emergency in many countries. Diabetic foot disease and, particularly diabetic foot ulceration, is the major complication of DM: through a skin damage of the foot, with a loss of epithelial tissue, it can deepen to muscles and bones and lead to the amputation of the lower limbs. Peripheral arterial disease (PAD) in patients with diabetes, manifests like a diffuse macroangiopathic multi-segmental involvement of the lower limb vessels, also connected to a damage of collateral circulation; it may also display characteristic microaneurysms and tortuosity in distal arteries. As validation method, Bold-MRI is used. The diabetic foot should be handled with a multidisciplinary team approach, as its management requires systemic and localized treatments, pain control, monitoring of cardiovascular risk factors and other comorbidities. CBCT is an emerging medical imaging technique with the original feature of divergent radiation, forming a cone, in contrast with the spiral slicing of conventional CT, and has become increasingly important in treatment planning and diagnosis: from small anatomical areas, such as implantology, to the world of interventional radiology, with a wide range of applications: as guidance for biopsies or ablation treatments. The aim of this project is to evaluate the usefulness of perfusion CBCT imaging, obtained during endovascular revascularization, for intraprocedural evaluation of endovascular treatment in patients with diabetic foot.
... [3][4][5][6] Because the baseline skeletal muscle perfusion at rest is relatively low, some research groups have developed stress BOLD perfusion imaging using different paradigms, such as gas inhalation, cuff compression-induced ischemia and postocclusive reactive hyperemia, and exercise. 4,5,7,8 All these paradigms can provoke BOLD signal alterations to measure skeletal muscle blood flow reserve. However, it still remains unclear whether one paradigm is an alternative to another, or whether one is superior to another. ...
Purpose
Stress blood oxygenation level‐dependent (BOLD) cardiovascular magnetic resonance allows for quantitative evaluation of blood flow reserve in skeletal muscles. This study aimed to prospectively compare three commonly used skeletal BOLD cardiovascular magnetic resonance paradigms in healthy adults: gas inhalation, cuff compression‐induced ischemia and postocclusive reactive hyperemia, and exercise.
Methods
Twelve young (22 ± 0.9 years) and 10 elderly (58 ± 5.0 years) healthy subjects underwent BOLD cardiovascular magnetic resonance under the three paradigms. T2∗ signal intensity time curves were generated and quantitative parameters were calculated. Meanwhile, stress transcutaneous oxygen pressure measurements were obtained as comparison. Measurement reproducibility was assessed with intraclass correlation coefficients. Differences in the T2∗ BOLD variation, the correlation with transcutaneous oxygen pressure, and the age‐related change between paradigms were statistically analyzed.
Results
Minimum ischemic value and maximum hyperemic peak value showed the highest interobserver and interscan reproducibilities (intraclass correlation coefficient >0.90). The plantar dorsiflexion exercise paradigm elicited the largest T2∗ BOLD variation (15.48% ± 10.56%), followed by ischemia (8.30% ± 6.33%). Negligible to weak changes were observed during gas inhalation. Correlations with transcutaneous oxygen pressure measurements were found in the ischemic phase (r = 0.966; P < .001) and in the postexercise phase (r = −0.936; P < .001). Minimum ischemic value, maximum hyperemic peak value, maximum postexercise value, and slope of postexercise signal decay showed significant differences between young and elderly subjects (P < .01).
Conclusion
Ischemia and reactive hyperemia have superior reproducibility, and exercise could induce the largest T2∗ variation. Key parameters from the two paradigms show age‐related differences.
... Blood oxygenation level-dependent imaging can evaluate skeletal muscle microcirculation Bold oxygenation level-dependent (BOLD) imaging is an MRI technique employed to evaluate the microcirculation of the brain, the cardiovascular system and skeletal muscle [11,[69][70][71]. This modality exploits the fact that haemoglobin iron changes its spin state depending on its oxygenation status and, in essence, assessed the ratio of oxyhaemoglobin to deoxyhaemoglobin [12]. ...
Introduction:
This study assesses the burden, distribution and evolution of muscle inflammation and damage on magnetic resonance imaging (MRI) amongst subtypes of idiopathic inflammatory myopathy (IIM).
Methods:
Musculoskeletal MRIs performed on 66 IIM patients and 10 patients with non-IIM between 2009- 2016 were retrospectively graded for muscle oedema, fatty replacement (FR) and atrophy.
Results:
Immune-mediated necrotising myopathy (IMNM) patients had severe and extensive lower limb muscle oedema, FR and atrophy. The pelvic muscles and adductors were significantly more affected than in dermatomyositis and polymyositis patients. Inclusion body myositis (IBM) was characterised by marked anterior thigh involvement, which stabilised or progressed on follow-up imaging. Atrophy and FR grades improved over time in some non-IBM IIM patients.
Discussion:
Patients with IMNM and IBM have characteristic patterns of muscle MRI abnormalities that may allow them to be differentiated radiologically from other IIM subtypes. Muscle damage in non-IBM IIM may be reversible. This article is protected by copyright. All rights reserved.
... The gastrocnemius is a fast-twitch type muscle, whereas the soleus belongs to the slow-twitch type. Degenerative processes of muscle fibers have been demonstrated to differ with fiber type, and the fast-twitch muscle is more prone to aging and fatigue [36,37]. The ABI is a measure providing objective data for diagnosing PAD. ...
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 muscle perfusion in lower extremities and to investigate their abilities to diagnose and assess the severity of peripheral arterial disease (PAD).
Methods:
Fifteen healthy young subjects, 14 patients with PAD, and 10 age-matched healthy old subjects underwent ASL, BOLD, and IVIM CMR perfusion imaging. Healthy young and healthy old participants were subjected to a cuff-induced ischemia experiment with pressures of 20 mmHg and 40 mmHg above systolic pressure during imaging. Perfusion-related metrics, including blood flow, T2* relaxation time, perfusion fraction f, diffusion coefficient D, and pseudodiffusion coefficient D*, were measured in the anterior, lateral, soleus, and gastrocnemius muscle groups. Friedman, Mann-Whitney, Wilcoxon signed rank, and Spearman rank correlation tests were used for statistical analysis.
Results:
In cases of significant differences determined by the Friedman test (P < 0.05), blood flow, T2*, and D values gradually decreased, while f values showed a tendency to increase in healthy subjects under cuff compression. No significant correlations were found among the ASL, BOLD, and IVIM parameters (all P > 0.05). Blood flow and T2* values showed significant positive correlations with transcutaneous oxygen pressure measurements (ρ = 0.465 and 0.522, respectively; both P ≤ 0.001), while f values showed a significant negative correlation in healthy young subjects (ρ = - 0.351; P = 0.018). T2* was independent of age in every muscle group. T2* values were significantly decreased in PAD patients compared with healthy old subjects and severe PAD patients compared with mild-to-moderate PAD patients (all P < 0.0125). Significant correlations were found between T2* and ankle-brachial index values in all muscle groups in PAD patients (ρ = 0.644-0.837; all P < 0.0125). Other imaging parameters failed to show benefits towards the diagnosis and disease severity evaluation of PAD.
Conclusions:
ASL, BOLD, and IVIM provide complementary information regarding tissue perfusion. Compared with ASL and IVIM, BOLD may be a more reliable technique for assessing PAD in the resting state and could thus be applied together with angiography in clinical studies as a tool to comprehensively assess microvascular and macrovascular properties in PAD patients.
... A CT value of 1 HU quantifies a density difference to water of 0.1%. The physical density of skeletal muscle, including IMCLs, is about 1.055 g/cm 3 [57e59] compared with 1 g/cm 3 for water. Thus, for a properly calibrated scanner, the CT value of skeletal muscle also termed as muscle tissue is about 50e60 HU. ...
The radiological assessment of muscle properties—size, mass, density (also termed radiodensity), composition, and adipose tissue infiltration—is fundamental in muscle diseases. More recently, it also became obvious that muscle atrophy, also termed muscle wasting, is caused by or associated with many other diseases or conditions, such as inactivity, malnutrition, chronic obstructive pulmonary disorder, cancer-associated cachexia, diabetes, renal and cardiac failure, and sarcopenia and even potentially with osteoporotic hip fracture. Several techniques have been developed to quantify muscle morphology and function. This review is dedicated to quantitative computed tomography (CT) of skeletal muscle and only includes a brief comparison with magnetic resonance imaging. Strengths and limitations of CT techniques are discussed in detail, including CT scanner calibration, acquisition and reconstruction protocols, and the various quantitative parameters that can be measured with CT, starting from simple volume measures to advanced parameters describing the adipose tissue distribution within muscle. Finally, the use of CT in sarcopenia and cachexia and the relevance of muscle parameters for the assessment of osteoporotic fracture illustrate the application of CT in two emerging areas of medical interest. Keywords: Adipose tissue, Computed tomography, Fat infiltration, Muscle, Muscle density
... Based on the magnetic properties of oxygenated (diamagnetic) and deoxygenated (paramagnetic) hemoglobin in blood, non-invasive magnetic resonance (MR) techniques have been previously described to estimate blood O2 saturation, myocardial and skeletal tissue oxygenation, and brain oxygen extraction fraction [5][6][7][8]. These methods exploit the dependence of MR relaxation times (T1, T2 and T2*) on the oxygen saturation of hemoglobin in blood [5,9,10]. ...
Background
Measurement of blood oxygen saturation (O2 saturation) is of great importance for evaluation of patients with many cardiovascular diseases, but currently there are no established non-invasive methods to measure blood O2 saturation in the heart. While T2-based CMR oximetry methods have been previously described, these approaches rely on technique-specific calibration factors that may not generalize across patient populations and are impractical to obtain in individual patients. We present a solution that utilizes multiple T2 measurements made using different inter-echo pulse spacings. These data are jointly processed to estimate all unknown parameters, including O2 saturation, in the Luz-Meiboom (L-M) model. We evaluated the accuracy of the proposed method against invasive catheterization in a porcine hypoxemia model.
Methods
Sufficient data diversity to estimate the various unknown parameters of the L-M model, including O2 saturation, was achieved by acquiring four T2 maps, each at a different τ180 (12, 15, 20, and 25 ms). Venous and arterial blood T2 values from these maps, together with hematocrit and arterial O2 saturation, were jointly processed to derive estimates for venous O2 saturation and other nuisance parameters in the L-M model. The technique was validated by a progressive graded hypoxemia experiment in seven pigs. CMR estimates of O2 saturation in the right ventricle were compared against a reference O2 saturation obtained by invasive catheterization from the right atrium in each pig, at each hypoxemia stage. O2 saturation derived from the proposed technique was also compared against the previously described method of applying a global calibration factor (K) to the simplified L-M model.
Results
Venous O2 saturation results obtained using the proposed CMR oximetry method exhibited better agreement (y = 0.84× + 12.29, R² = 0.89) with invasive blood gas analysis when compared to O2 saturation estimated by a global calibration method (y = 0.69× + 27.52, R² = 0.73).
Conclusions
We have demonstrated a novel, non-invasive method to estimate O2 saturation using quantitative T2 mapping. This technique may provide a valuable addition to the diagnostic utility of CMR in patients with congenital heart disease, heart failure, and pulmonary hypertension.
... Magnetic resonance imaging (MRI) uses the T 1 and T 2 of contrast agents to distinguish different types of tissue based on proton relaxation time differences. In blood oxygen level dependent (BOLD) MRI (6,(49)(50)(51), the differential oxygenation of hemoglobin during functional activation of the brain and the consequent magnetic susceptibility difference that depends on the ratio of hemoglobin to deoxyhemoglobin change the local relaxation time to produce the contrast. Molecular oxygen itself is a paramagnetic species with two unpaired electrons, and can also shorten proton T 1 . ...
Significance:
Electron Paramagnetic Resonance imaging (EPRI) is a powerful technique capable of generating images of tissue oxygenation using exogenous paramagnetic probes such as trityl radicals or nitroxyl radicals. Using principles similar to Magnetic Resonance Imaging (MRI) with field gradients, the spatial distribution of the paramagnetic probecan be generatedand,from its spectral features, spatial maps of oxygen can be obtained from live objects. In this review, two methods of signal acquisition, image formation/reconstruction will be described. The probes used and its application to study tumor physiology and monitor treatment response with chemotherapy drugs in mouse models of human cancer will be summarized. Recent Advances: By implementing phase encoding/Fourier reconstruction in EPRI in time-domain mode, the frequency contribution to the spatial resolution was avoided and improved images wereobtained. The high resolution EPRI revealed the pO2 changesin tumor, which was useful to detect and evaluate the effects of various anti-tumor therapies. Coregistration with other imaging modalities provided a better understanding of hypoxia related alteration in physiology.
Critical issues:
The high radiofrequency (RF) power of EPR irradiation and toxicity profile of radical probes are the main obstacles for clinical application. The improvement of RF low power pulse sequencesmayallow for clinical translation.
Future directions:
Pulsed EPR oximetry canbe a powerful tool to research various disease involving hypoxia such as cancer, ischemic heart diseases, stroke, and diabetes. By optimizing radical probes, it can also be applied for various other purposes such as detecting local acid-base balance or oxidative stress.
... Invasive methods involve oxygen sensitive electrodes such as the Clark electrode (51,54) or the Eppendorf electrode (127,130). As noninvasive methods, the blood oxygenation leveldependent MRI techniques (16,96,99) where a T 2 *-sensitive gradient echo pulse sequence is used to visualize the ratio between oxy/deoxy-hemoglobin and nonhydrogen nuclei such as 17 O (89, 97, 136) or 19 F MR images (88,101,107) where the oxygen concentration is reflected in the signal intensity of the image are available. ...
Significance:
Proton-electron double resonance imaging (PEDRI) employs electron paramagnetic resonance irradiation with low field magnetic resonance imaging (MRI) so that the electron spin polarization is transferred to nearby protons, resulting in higher signal. PEDRI provides information about free radical distribution and, indirectly, about the local microenvironment such as pO2, tissue permeability, redox status, and acid-base balance. Recent Advances: Local acid-base balance can be imaged by exploiting the different resonance frequency of radical probes between R and RH+ forms. Redox status can also be imaged using the loss of radical-related signal after reduction. These methods require optimized radical probes and pulse sequences.
Critical issues:
High power radiofrequency irradiation is needed for optimum signal enhancement, which may be harmful to living tissue by unwanted heat deposition. Free radical probes differ depending on the purpose of PEDRI. Some probes are less effective for enhancing signal than others, which can reduce image quality. It is so far not possible to image endogenous radicals by PEDRI because low concentrations and broad line widths of the radicals lead to negligible signal enhancement.
Future directions:
PEDRI has similarities with electron paramagnetic resonance imaging (EPRI) because both otechniques bserve the EPR signal; directly in the case of EPRI and indirectly with PEDRI. PEDRI provides information vital to research on homeostasis, development of diseases or treatment responses in vivo. It is expected that the development of new EPR techniques will give insights into novel PEDRI applications and vice versa.
