DCS blood flow index underestimates skeletal muscle perfusion in vivo: rationale and early evidence for the NIRS-DCS perfusion index.

Significance: Diffuse correlation spectroscopy (DCS) permits non-invasive assessment of skeletal muscle blood flow but may misestimate changes in muscle perfusion. Aim: We aimed to highlight recent evidence that DCS blood flow index (BFI) misestimates changes in muscle blood flow during physiological perturbation and to introduce a novel approach that adjusts BFI for estimated changes in vasodilation. Approach: We measured changes in muscle BFI during quadriceps and forearm exercises using DCS, the latter of which were adjusted for estimated changes in microvascular flow area and then compared to Doppler ultrasound in the brachial artery. Then, we compared adjusted BFI- and arterial spin labeling (ASL) MRI measures of gastrocnemius blood flow during reactive hyperemia and plantar flexion exercise. Results: We observed little-to-no change in quadriceps BFI during maximal-effort exercise. Similarly, forearm BFI was modestly increased during handgrip exercise, but the magnitude was significantly lower than measured by Doppler ultrasound in the brachial artery. However, this difference was ameliorated after adjusting BFI for estimated changes in microvascular flow area. Similar observations were also observed in the gastrocnemius when directly comparing the adjusted BFI values to ASL-MRI. Conclusions: Adjusting BFI for estimated changes in microvascular flow area may improve DCS estimates of muscle blood flow, but further study is needed to validate these methods moving forward.

Computed tomographic findings in TBX4 mutation: a common cause of severe pulmonary artery hypertension in children.

BACKGROUND: Mutations in the T-Box 4 (TBX4) gene are a lesser-known cause of heritable pulmonary arterial hypertension (PAH). Patients with heritable PAH typically have worse outcomes when compared with patients with idiopathic PAH, yet little is known about the phenotypical presentation of this mutation. OBJECTIVE: This article reviews the pattern of chest CT findings in pediatric patients with PAH and TBX4 mutations and compares their radiographic presentation with those of age-matched patients with PAH but without TBX4 mutations. MATERIALS AND METHODS: A retrospective chart review of the pulmonary arterial hypertension database was performed. Pediatric patients with PAH-confirmed TBX4 mutations and an available high CT were included. Fifteen (9 females) patients met the inclusion criteria. Fourteen (8 females) age-matched controls with diagnosed PAH but without TBX4 mutations were also evaluated. The median age at diagnosis was 7.4 years (range: 0.1-16.4 years). Demographic information and clinical outcomes were collected. CTs of the chest were reviewed for multiple airway, parenchymal, and structural abnormalities (16 imaging findings in total). Chi-square tests were used to compare the prevalence of each imaging finding in the TBX4 cohort compared to the control group. RESULTS: Patients with TBX-4 mutations had increased presence of peripheral or subpleural irregularity (73% vs 0%, P < 0.01), cystic lucencies (67% vs 7%, P < 0.01), and linear or reticular opacity (53% vs 0%, P < 0.01) compared to the control group. Ground glass opacities, bronchiectasis, and centrilobular nodules were not significantly different between the two patient groups (P > 0.05). CONCLUSION: TBX4 mutations have distinct imaging phenotypes in pediatric patients with PAH. Compared to patients without this mutation, patients with TBX-4 genes typically present with peripheral or subpleural irregularity, cystic lucencies, and linear or reticular opacity.

Reference Values for Fetal Cardiac Dimensions, Volumes, Ventricular Function and Left Ventricular Longitudinal Strain Using Doppler Ultrasound Gated Cardiac Magnetic Resonance Imaging in Healthy Third Trimester Fetuses.

BACKGROUND: Recent advances in hardware and software permit the use of cardiac MRI of late gestation fetuses, however there is a paucity of MRI-based reference values. PURPOSE: To provide initial data on fetal cardiac MRI-derived cardiac dimensions, volumes, ventricular function, and left ventricular longitudinal strain in healthy developing fetuses >30 weeks gestational age. STUDY TYPE: Prospective. POPULATION: Twenty-five third trimester (34 ± 1 weeks, range of 32-37 weeks gestation) women with healthy developing fetuses. FIELD STRENGTH/SEQUENCE: Studies were performed at 1.5 T and 3 T. Cardiac synchronization was achieved with a Doppler ultrasound device. The protocol included T2 single shot turbo spin echo stacks for fetal weight and ultrasound probe positioning, and multiplanar multi-slice cine balanced steady state free precession gradient echo sequences. ASSESSMENT: Primary analyses were performed by a single observer. Weight indexed right ventricular (RV) and left ventricular (LV) volumes and function were calculated from short axis (SAX) stacks. Cardiac dimensions were calculated from the four-chamber and SAX stacks. Single plane LV longitudinal strain was calculated from the four-chamber stack. Interobserver variability was assessed in 10 participants. Cardiac MRI values were compared against available published normative fetal echocardiogram data using z-scores. STATISTICAL TESTS: Mean and SDs were calculated for baseline maternal/fetal demographics, cardiac dimensions, volumes, ventricular function, and left ventricular longitudinal strain. Bland-Altman and intraclass correlation coefficient analysis was performed to test interobserver variability. RESULTS: The mean gestational age was 34 ± 1.4 weeks. The mean RV and LV end diastolic volumes were 3.1 ± 0.6 mL/kg and 2.4 ± 0.5 mL/kg respectively. The mean RV cardiac output was 198 ± 49 mL/min/kg while the mean LV cardiac output was 173 ± 43 mL/min/kg. DATA CONCLUSION: This paper reports initial reference values obtained by cardiac MRI in healthy developing third trimester fetuses. MRI generally resulted in slightly larger indexed values (by z-score) compared to reports in literature using fetal echocardiography. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Obesity dominates early effects on cardiac structure and arterial stiffness in people with type 2 diabetes.

OBJECTIVE: Type 2 diabetes (T2D) and obesity are global epidemics leading to excess cardiovascular disease (CVD). This study investigates standard and novel cardiac MRI parameters to detect subclinical cardiac and central vascular dysfunction in inactive people with and without T2D. METHODS: Physically inactive age and BMI-similar premenopausal women and men with ( n  = 22) and without [ n  = 34, controls with overweight/obesity (CWO)] uncomplicated T2D were compared to an age-similar and sex-similar reference control cohort ( n  = 20). Left ventricular (LV) structure, function, and aortic stiffness were assessed by MRI. Global arterial pulse wave velocity (PWV) was assessed using carotid-to-femoral applanation tonometry. Regional PWV was measured via 2D phase-contrast MRI and 4D flow MRI. RESULTS: Global arterial PWV did not differ between CWO and T2D. 2D PC-MRI PWV in the ascending aorta was higher in people with T2D compared with CWOs ( P  < 0.01). 4D flow PWV in the thoracic aorta was higher in CWO ( P  < 0.01), and T2D ( P  < 0.001) compared with RC. End-diastolic volume, end-systolic volume, stroke volume, and cardiac output were lower in CWO and T2D groups compared with reference control. CONCLUSION: Subclinical changes in arterial stiffening and cardiac remodeling in inactive CWO and T2D compared with reference control support obesity and/or physical inactivity as determinants of incipient CVD complications in uncomplicated T2D. Future studies should determine the mechanistic causes of the CVD complications in greater detail in order to create therapeutic targets. CLINICAL TRIAL REGISTRATION: Cardiovascular Mechanisms of Exercise Intolerance in Diabetes and the Role of Sex (NCT03419195).

Computed tomographic parenchymal lung findings in premature infants with pulmonary vein stenosis.

BACKGROUND: Developmental pulmonary vein pulmonary vein stenosis in the setting of prematurity is a rare and poorly understood condition. Diagnosis can be challenging in the setting of chronic lung disease of prematurity. High-resolution non-contrast chest computed tomography (CT) is the conventional method of evaluating neonates for potential structural changes contributing to severe lung dysfunction and pulmonary hypertension but may miss pulmonary venous stenosis due to the absence of contrast and potential overlap in findings between developmental pulmonary vein pulmonary vein stenosis and lung disease of prematurity. OBJECTIVE: To describe the parenchymal changes of pediatric patients with both prematurity and pulmonary vein stenosis, correlate them with venous disease and to describe the phenotypes associated with this disease. MATERIALS AND METHODS: A 5-year retrospective review of chest CT angiography (CTA) imaging in patients with catheterization-confirmed pulmonary vein stenosis was performed to identify pediatric patients (< 18 years) who had a history of prematurity (< 35 weeks gestation). Demographic and clinical data associated with each patient were collected, and the patients' CTAs were re-reviewed to evaluate pulmonary veins and parenchyma. Patients with post-operative pulmonary vein stenosis and those with congenital heart disease were excluded. Data was analyzed and correlated for descriptive purposes. RESULTS: A total of 17 patients met the inclusion criteria (12 female, 5 male). All had pulmonary hypertension. There was no correlation between mild, moderate, and severe grades of bronchopulmonary dysplasia and the degree of pulmonary vein stenosis. There was a median of 2 (range 1-4) diseased pulmonary veins per patient. In total, 41% of the diseased pulmonary veins were atretic. The right upper and left upper lobe pulmonary veins were the most frequently diseased (n = 13/17, 35%, n = 10/17, 27%, respectively). Focal ground glass opacification, interlobular septal thickening, and hilar soft tissue enlargement were always associated with the atresia of an ipsilateral vein. CONCLUSION: Recognition of the focal parenchymal changes that imply pulmonary vein stenosis, rather than chronic lung disease of prematurity changes, may improve the detection of a potentially treatable source of pulmonary hypertension, particularly where nonangiographic studies result in a limited direct venous assessment.

Update on state-of-the-art for arterial spin labeling (ASL) human perfusion imaging outside of the brain.

This review article provides an overview of developments for arterial spin labeling (ASL) perfusion imaging in the body (i.e., outside of the brain). It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. In this review, we focus on specific challenges and developments tailored for ASL in a variety of body locations. After presenting common challenges, organ-specific reviews of challenges and developments are presented, including kidneys, lungs, heart (myocardium), placenta, eye (retina), liver, pancreas, and muscle, which are regions that have seen the most developments outside of the brain. Summaries and recommendations of acquisition parameters (when appropriate) are provided for each organ. We then explore the possibilities for wider adoption of body ASL based on large standardization efforts, as well as the potential opportunities based on recent advances in high/low-field systems and machine-learning. This review seeks to provide an overview of the current state-of-the-art of ASL for applications in the body, highlighting ongoing challenges and solutions that aim to enable more widespread use of the technique in clinical practice.

IVIM Imaging of Paraspinal Muscles Following Moderate and High-Intensity Exercise in Healthy Individuals.

Background: Quantification of the magnitude and spatial distribution of muscle blood flow changes following exercise may improve our understanding of the effectiveness of various exercise prescriptions. Intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) is a technique that quantifies molecular diffusion and microvascular blood flow, and has recently gained momentum as a method to evaluate a muscle's response to exercise. It has also been shown to predict responses to exercise-based physical therapy in individuals with low back pain. However, no study has evaluated the sensitivity of IVIM-MRI to exercise of varying intensity in humans. Here, we aimed to evaluate IVIM signal changes of the paraspinal muscles in response to moderate and high intensity lumbar extension exercise in healthy individuals. Methods: IVIM data were collected in 11 healthy volunteers before and immediately after a 3-min bout of moderate and high-intensity resisted lumbar extension. IVIM data were analyzed to determine the average perfusion fraction (f), pseudo-diffusion coefficient (D*), and diffusion coefficient (D) in the bilateral paraspinal muscles. Changes in IVIM parameters were compared between the moderate and high intensity exercise bouts. Results: Exercise increased all IVIM parameters, regardless of intensity (p < 0.003). Moderate intensity exercise resulted in a 11.2, 19.6, and 3.5% increase in f, D* and D, respectively. High intensity exercise led to a similar increase in f (12.2%), but much greater changes in D* (48.6%) and D (7.9%). Conclusion: IVIM parameter increases suggest that both the moderate and high-intensity exercise conditions elicited measurable changes in blood flow (increased f and D*) and extravascular molecular diffusion rates (increased D), and that there was a dose-dependence of exercise intensity on D* and D.

Impact of supervised exercise on skeletal muscle blood flow and vascular function measured with MRI in patients with peripheral artery disease.

Supervised exercise is a common therapeutic intervention for patients with peripheral artery disease (PAD), however, the mechanism underlying the improvement in claudication symptomatology is not completely understood. The hypothesis that exercise improves microvascular blood flow is herein tested via temporally resolved magnetic resonance imaging (MRI) measurement of blood flow and oxygenation dynamics during reactive hyperemia in the leg with the lower ankle-brachial index. One hundred and forty-eight subjects with PAD were prospectively assigned to standard medical care or 3 mo of supervised exercise therapy. Before and after the intervention period, subjects performed a graded treadmill walking test, and MRI data were collected with Perfusion, Intravascular Venous Oxygen saturation, and T2* (PIVOT), a method that simultaneously quantifies microvascular perfusion, as well as relative oxygenation changes in skeletal muscle and venous oxygen saturation in a large draining vein. The 3-mo exercise intervention was associated with an improvement in peak walking time (64% greater in those randomized to the exercise group at follow-up, P < 0.001). Significant differences were not observed in the MRI measures between the subjects randomized to exercise therapy versus standard medical care based on an intention-to-treat analysis. However, the peak postischemia perfusion averaged across the leg between baseline and follow-up visits increased by 10% (P = 0.021) in participants that were adherent to the exercise protocol (completed >80% of prescribed exercise visits). In this cohort of adherent exercisers, there was no difference in the time to peak perfusion or oxygenation metrics, suggesting that there was no improvement in microvascular function nor changes in tissue metabolism in response to the 3-mo exercise intervention.NEW & NOTEWORTHY Supervised exercise interventions can improve symptomatology in patients with peripheral artery disease, but the underlying mechanism remains unclear. Here, MRI was used to evaluate perfusion, relative tissue oxygenation, and venous oxygen saturation in response to cuff-induced ischemia. Reactive hyperemia responses were measured before and after 3 mo of randomized supervised exercise therapy or standard medical care. Those participants who were adherent to the exercise regimen had a significant improvement in peak perfusion.

A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO2) with single gas calibrated fMRI.

One promising approach for mapping CMRO2 is dual-calibrated functional MRI (dc-fMRI). This method exploits the Fick Principle to combine estimates of CBF from ASL, and OEF derived from BOLD-ASL measurements during arterial O2 and CO2 modulations. Multiple gas modulations are required to decouple OEF and deoxyhemoglobin-sensitive blood volume. We propose an alternative single gas calibrated fMRI framework, integrating a model of oxygen transport, that links blood volume and CBF to OEF and creates a mapping between the maximum BOLD signal, CBF and OEF (and CMRO2). Simulations demonstrated the method's viability within physiological ranges of mitochondrial oxygen pressure, PmO2, and mean capillary transit time. A dc-fMRI experiment, performed on 20 healthy subjects using O2 and CO2 challenges, was used to validate the approach. The validation conveyed expected estimates of model parameters (e.g., low PmO2), with spatially uniform OEF maps (grey matter, GM, OEF spatial standard deviation ≈ 0.13). GM OEF estimates obtained with hypercapnia calibrated fMRI correlated with dc-fMRI (r = 0.65, p = 2·10-3). For 12 subjects, OEF measured with dc-fMRI and the single gas calibration method were correlated with whole-brain OEF derived from phase measures in the superior sagittal sinus (r = 0.58, p = 0.048; r = 0.64, p = 0.025 respectively). Simplified calibrated fMRI using hypercapnia holds promise for clinical application.

Free-breathing magnetic resonance imaging with radial k-space sampling for neonates and infants to reduce anesthesia.

BACKGROUND: Conventional chest and abdominal MRI require breath-holds to reduce motion artifacts. Neonates and infants require general anesthesia with intubation to enable breath-held acquisitions. OBJECTIVE: We aimed to validate a free-breathing approach to reduce general anesthesia using a motion-insensitive radial acquisition with respiratory gating. MATERIALS AND METHODS: We retrospectively enrolled children <3 years old who were referred for MRI of the chest or abdomen. They were divided into two groups according to MRI protocol: (1) breath-held scans under general anesthesia with T2-weighted single-shot fast spin-echo (SSFSE) and contrast-enhanced T1-weighted modified Dixon, and (2) free-breathing scans using radial sequences (T2-W MultiVane XD and contrast-enhanced T1-W three-dimensional [3-D] Vane XD). Two readers graded image quality and motion artifacts. RESULTS: We included 23 studies in the free-breathing cohort and 22 in the breath-hold cohort. The overall imaging scores for the free-breathing radial T2-W sequence were similar to the scores for the breath-held T2-W SSFSE sequence (chest, 3.6 vs. 3.2, P=0.07; abdomen, 3.9 vs. 3.7, P=0.66). The free-breathing 3-D radial T1-W sequence also had image quality scores that were similar to the breath-held T1-W sequence (chest, 4.0 vs. 3.0, P=0.06; abdomen, 3.7 vs. 3.9, P=0.15). Increased motion was seen in the abdomen on the radial T2-W sequence (P<0.001), but increased motion was not different in the chest (P=0.73) or in contrast-enhanced T1-W sequences (chest, P=0.39; abdomen, P=0.15). The mean total sequence time was longer in free-breathing compared to breath-held exams (P<0.01); however, this did not translate to longer overall exam times (P=0.94). CONCLUSION: Motion-insensitive radial sequences used for infants and neonates were of similar image quality to breath-held sequences and had decreased sedation and intubation.

MRI evaluation of cerebral metabolic rate of oxygen (CMRO2) in obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) are at elevated risk of developing systemic vascular disease and cognitive dysfunction. Here, cerebral oxygen metabolism was assessed in patients with OSA by means of a magnetic resonance-based method involving simultaneous measurements of cerebral blood flow rate and venous oxygen saturation in the superior sagittal sinus for a period of 10 minutes at an effective temporal resolution of 1.3 seconds before, during, and after repeated 24-second breath-holds mimicking spontaneous apneas, yielding, along with pulse oximetry-derived arterial saturation, whole-brain CMRO2 via Fick's Principle. Enrolled subjects were classified based on their apnea-hypopnea indices into OSA (N = 31) and non-sleep apnea reference subjects (NSA = 21), and further compared with young healthy subjects (YH, N = 10). OSA and NSA subjects were matched for age and body mass index. CMRO2 was lower in OSA than in the YH group during normal breathing (105.6 ± 14.1 versus 123.7 ± 22.8 µmol O2/min/100g, P = 0.01). Further, the fractional change in CMRO2 in response to a breath-hold challenge was larger in OSA than in the YH group (15.2 ± 9.2 versus 8.5 ± 3.4%, P = 0.04). However, there was no significant difference in CMRO2 between OSA and NSA subjects. The data suggest altered brain oxygen metabolism in OSA and possibly in NSA as well.

Intravoxel Incoherent Motion Magnetic Resonance Imaging in Skeletal Muscle: Review and Future Directions.

Throughout the body, muscle structure and function can be interrogated using a variety of noninvasive magnetic resonance imaging (MRI) methods. Recently, intravoxel incoherent motion (IVIM) MRI has gained momentum as a method to evaluate components of blood flow and tissue diffusion simultaneously. Much of the prior research has focused on highly vascularized organs, including the brain, kidney, and liver. Unique aspects of skeletal muscle, including the relatively low perfusion at rest and large dynamic range of perfusion between resting and maximal hyperemic states, may influence the acquisition, postprocessing, and interpretation of IVIM data. Here, we introduce several of those unique features of skeletal muscle; review existing studies of IVIM in skeletal muscle at rest, in response to exercise, and in disease states; and consider possible confounds that should be addressed for muscle-specific evaluations. Most studies used segmented nonlinear least squares fitting with a b-value threshold of 200 sec/mm2 to obtain IVIM parameters of perfusion fraction (f), pseudo-diffusion coefficient (D*), and diffusion coefficient (D). In healthy individuals, across all muscles, the average ± standard deviation of D was 1.46 ± 0.30 × 10-3  mm2 /sec, D* was 29.7 ± 38.1 × 10-3  mm2 /sec, and f was 11.1 ± 6.7%. Comparisons of reported IVIM parameters in muscles of the back, thigh, and leg of healthy individuals showed no significant difference between anatomic locations. Throughout the body, exercise elicited a positive change of all IVIM parameters. Future directions including advanced postprocessing models and potential sequence modifications are discussed. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Segmentation of the Aorta and Pulmonary Arteries Based on 4D Flow MRI in the Pediatric Setting Using Fully Automated Multi-Site, Multi-Vendor, and Multi-Label Dense U-Net.

BACKGROUND: Automated segmentation using convolutional neural networks (CNNs) have been developed using four-dimensional (4D) flow magnetic resonance imaging (MRI). To broaden usability for congenital heart disease (CHD), training with multi-institution data is necessary. However, the performance impact of heterogeneous multi-site and multi-vendor data on CNNs is unclear. PURPOSE: To investigate multi-site CNN segmentation of 4D flow MRI for pediatric blood flow measurement. STUDY TYPE: Retrospective. POPULATION: A total of 174 subjects across two sites (female: 46%; N = 38 healthy controls, N = 136 CHD patients). Participants from site 1 (N = 100), site 2 (N = 74), and both sites (N = 174) were divided into subgroups to conduct 10-fold cross validation (10% for testing, 90% for training). FIELD STRENGTH/SEQUENCE: 3 T/1.5 T; retrospectively gated gradient recalled echo-based 4D flow MRI. ASSESSMENT: Accuracy of the 3D CNN segmentations trained on data from single site (single-site CNNs) and data across both sites (multi-site CNN) were evaluated by geometrical similarity (Dice score, human segmentation as ground truth) and net flow quantification at the ascending aorta (Qs), main pulmonary artery (Qp), and their balance (Qp/Qs), between human observers, single-site and multi-site CNNs. STATISTICAL TESTS: Kruskal-Wallis test, Wilcoxon rank-sum test, and Bland-Altman analysis. A P-value <0.05 was considered statistically significant. RESULTS: No difference existed between single-site and multi-site CNNs for geometrical similarity in the aorta by Dice score (site 1: 0.916 vs. 0.915, P = 0.55; site 2: 0.906 vs. 0.904, P = 0.69) and for the pulmonary arteries (site 1: 0.894 vs. 0.895, P = 0.64; site 2: 0.870 vs. 0.869, P = 0.96). Qs site-1 medians were 51.0-51.3 mL/cycle (P = 0.81) and site-2 medians were 66.7-69.4 mL/cycle (P = 0.84). Qp site-1 medians were 46.8-48.0 mL/cycle (P = 0.97) and site-2 medians were 76.0-77.4 mL/cycle (P = 0.98). Qp/Qs site-1 medians were 0.87-0.88 (P = 0.97) and site-2 medians were 1.01-1.03 (P = 0.43). Bland-Altman analysis for flow quantification found equivalent performance. DATA CONCLUSION: Multi-site CNN-based segmentation and blood flow measurement are feasible for pediatric 4D flow MRI and maintain performance of single-site CNNs. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Exercise Training Increases Resting Calf Muscle Oxygen Metabolism in Patients with Peripheral Artery Disease.

Exercise training can mitigate symptoms of claudication (walking-induced muscle pain) in patients with peripheral artery disease (PAD). One adaptive response enabling this improvement is enhanced muscle oxygen metabolism. To explore this issue, we used arterial-occlusion diffuse optical spectroscopy (AO-DOS) to measure the effects of exercise training on the metabolic rate of oxygen (MRO2) in resting calf muscle. Additionally, venous-occlusion DOS (VO-DOS) and frequency-domain DOS (FD-DOS) were used to measure muscle blood flow (F) and tissue oxygen saturation (StO2), and resting calf muscle oxygen extraction fraction (OEF) was calculated from MRO2, F, and blood hemoglobin. Lastly, the venous/arterial ratio (γ) of blood monitored by FD-DOS was calculated from OEF and StO2. PAD patients who experience claudication (n = 28) were randomly assigned to exercise and control groups. Patients in the exercise group received 3 months of supervised exercise training. Optical measurements were obtained at baseline and at 3 months in both groups. Resting MRO2, OEF, and F, respectively, increased by 30% (12%, 44%) (p < 0.001), 17% (6%, 45%) (p = 0.003), and 7% (0%, 16%) (p = 0.11), after exercise training (median (interquartile range)). The pre-exercise γ was 0.76 (0.61, 0.89); it decreased by 12% (35%, 6%) after exercise training (p = 0.011). Improvement in exercise performance was associated with a correlative increase in resting OEF (R = 0.45, p = 0.02).

Intravoxel incoherent motion imaging predicts exercise-based rehabilitation response in individuals with low back pain.

Exercises to strengthen and stabilize the trunk musculature are a common conservative treatment strategy for low back pain (LBP), despite the possible presence of impairments in muscle activation in this population. Intravoxel incoherent motion (IVIM) MRI permits evaluation of activation-induced blood flow through diffusion-weighted images that are sensitized to microvascular blood flow. In the current study we aimed to evaluate IVIM signal changes after exercise in patients with LBP compared with pain-free healthy controls and determine if these changes were related to reductions in disability with a 12-week rehabilitation program. We hypothesize that the magnitude of changes in IVIM parameters in the lumbar extensor muscles will be smaller in patients with LBP compared with those without LBP, and that these magnitudes will be correlated with responsiveness to a 12-week, resistance-based exercise program. IVIM MR data for molecular diffusion (D), blood flow pseudodiffusion (D*) and perfusion fraction (f) were collected before and immediately after an ~ 3-min session of high-intensity lumbar extension resistance exercise in 16 healthy participants and 17 participants with LBP. Improvements in LBP-related disability after the 12-week, machine-based, high-intensity exercise rehabilitation program were measured in the LBP group. We observed a significant increase in all IVIM parameters (f, D*, D) in response to exercise (p < 0.0001) and an interaction of group-by-time for D (p = 0.016). Thresholds were identified using receiver operating characteristic (ROC) curves for diffusion and pseudodiffusion coefficients, which predicted a reduction in LBP-related disability in response to the 12-week, exercise-based rehabilitation program. Exercise was associated with an increase in (f), capillary blood flow-based pseudodiffusion (D*) and diffusion coefficient (D), regardless of the presence of LBP. Additionally, subgroup analysis identified patients who were not responsive to the acute exercise session, for whom, based on ROC analysis, there was no clinically significant change in disability following the 12-week program.

The influence of 3D curve severity on paraspinal muscle fatty infiltration in patients with adolescent idiopathic scoliosis.

PURPOSE: In a sex-inclusive cohort of patients with adolescent idiopathic scoliosis (AIS): (1) assess the relationship between 3D curve severity, curve flexibility, and paraspinal muscle fatty infiltration, and (2) describe three-dimensional (3D) fatty infiltration of the paraspinal muscles. METHODS: Fat signal fraction of the paravertebral muscles was measured in pre-operative magnetic resonance images (MRIs) of males and females with AIS at the apex, ± 1, and ± 2 levels from the apex of the curve (n = 62). In a subset of patients with biplanar erect radiographic imaging (n = 35), 3D measures of deformity (axial rotation of the apical vertebrae, thoracic kyphosis, and coronal Cobb angle) were measured. RESULTS: Contrary to previous studies, no relationship between coronal Cobb angle and fatty infiltration was found. However, axial apical rotation and sagittal Cobb angle were found to be significant predictors of paravertebral fatty infiltration (R2 = 0.196-0.222). Curve concavity, female sex, and proximity to the curve apex were found to be the strongest predictors of fatty infiltration. Greater fatty infiltration of the paravertebral muscles was found on the concave side of the curve (15-24% vs. 11-13%), with increasing fatty infiltration toward the apex of the curve. Fatty infiltration was protected on the convex side of the curve, with no differences in the amount of fatty infiltration across levels. CONCLUSION: These findings highlight that coronal curve severity and flexibility are not the primary influencing factors for the degree of paraspinal fatty infiltration in patients with AIS. This may have implications for nonsurgical rehabilitation strategies such as bracing and physical therapy. LEVEL OF EVIDENCE: II.

Medical imaging of tissue engineering and regenerative medicine constructs.

Advancement of tissue engineering and regenerative medicine (TERM) strategies to replicate tissue structure and function has led to the need for noninvasive assessment of key outcome measures of a construct's state, biocompatibility, and function. Histology based approaches are traditionally used in pre-clinical animal experiments, but are not always feasible or practical if a TERM construct is going to be tested for human use. In order to transition these therapies from benchtop to bedside, rigorously validated imaging techniques must be utilized that are sensitive to key outcome measures that fulfill the FDA standards for TERM construct evaluation. This review discusses key outcome measures for TERM constructs and various clinical- and research-based imaging techniques that can be used to assess them. Potential applications and limitations of these techniques are discussed, as well as resources for the processing, analysis, and interpretation of biomedical images.

Varying diffusion time to discriminate between simulated skeletal muscle injury models using stimulated echo diffusion tensor imaging.

PURPOSE: Evaluate the relationship between muscle microstructure, diffusion time (Δ), and the diffusion tensor (DT) to identify the optimal Δ where changes in muscle fiber size may be detected. METHODS: The DT was simulated in models with histology informed geometry over a range of Δ with a stimulated echo DT imaging (DTI) sequence using the numerical simulation application DifSim. The difference in the DT at each Δ between healthy and injured skeletal muscle models was calculated, to identify the optimal Δ at which changes in muscle fiber size may be detected. The random permeable barrier model (RPBM) was used to estimate muscle microstructure from the simulated DT measurements, which were compared to the ground truth. RESULTS: Across all models, fractional anisotropy provided greater contrast between injured and control models than diffusivity measurements. Compared to control models, in atrophic injury models, the greatest difference in the DT was found between 90 ms and 250 ms. In models with acute edema, the contrast between injured and control muscle increased with increasing diffusion time, although these models had smaller mean fiber areas. RPBM systematically underestimated fiber size but accurately estimated surface area-to-volume ratio of simulated models. CONCLUSION: These findings may better inform pulse sequence parameter selection when performing DTI experiments in vivo. If only a single diffusion experiment can be performed, the selected Δ should be ~170 ms to maximize the ability to discriminate between different injury models. Ideally several diffusion times between 90 ms and 500 ms should be sampled in order to maximize diffusion contrast, particularly when the disease process is unknown.

Multiparametric MRI characterization of level dependent differences in lumbar muscle size, quality, and microstructure.

Magnetic resonance imaging (MRI) is a diagnostic tool that can be used to noninvasively assess lumbar muscle size and fatty infiltration, important biomarkers of muscle health. Diffusion tensor imaging (DTI) is an MRI technique that is sensitive to muscle microstructural features such as fiber size (an important biomarker of muscle health), which is typically only assessed using invasive biopsy techniques. The goal of this study was to establish normative values of level-dependent lumbar muscle size, fat signal fraction, and restricted diffusion assessed by MRI in a highly active population. Forty-two active-duty Marines were imaged using a (a) high-resolution anatomical, (b) fat-water separation, and (c) DT-MRI scan. The multifidus and erector spinae muscles were compared at each level using two-way repeated measures ANOVA. Secondary analysis included Three dimensional (3D) reconstructions to qualitatively assess lumbar muscle size, fatty infiltration, and fiber orientation via tractography. The erector spinae was found to be larger than the multifidus above L5, with lower fat signal fraction above L3, and a less restricted diffusion profile than the multifidus above L4, with this pattern reversed in the lower lumbar spine. 3D reconstructions demonstrated accumulations of epimuscular fat in the anterior and posterior regions of the lumbar musculature, with minimal intramuscular fatty infiltration. Tractography images demonstrated different orientations of adjacent lumbar musculature, which cannot be visualized with standard MRI pulse sequences. The level dependent differences found in this study provide a normative baseline, for which to better understand whole muscle and microstructural changes associated with aging, low back pain, and pathology.

Quantitative and Dynamic MRI Measures of Peripheral Vascular Function.

The endothelium regulates and mediates vascular homeostasis, allowing for dynamic changes of blood flow in response to mechanical and chemical stimuli. Endothelial dysfunction underlies many diseases and is purported to be the earliest pathologic change in the progression of atherosclerotic disease. Peripheral vascular function can be interrogated by measuring the response kinetics following induced ischemia or exercise. In the presence of endothelial dysfunction, there is a blunting and delay of the hyperemic response, which can be measured non-invasively using a variety of quantitative magnetic resonance imaging (MRI) methods. In this review, we summarize recent developments in non-contrast, proton MRI for dynamic quantification of blood flow and oxygenation. Methodologic description is provided for: blood oxygenation-level dependent (BOLD) signal that reflect combined effect of blood flow and capillary bed oxygen content; arterial spin labeling (ASL) for quantification of regional perfusion; phase contrast (PC) to quantify arterial flow waveforms and macrovascular blood flow velocity and rate; high-resolution MRI for luminal flow-mediated dilation; and dynamic MR oximetry to quantify oxygen saturation. Overall, results suggest that these dynamic and quantitative MRI methods can detect endothelial dysfunction both in the presence of overt cardiovascular disease (such as in patients with peripheral artery disease), as well as in sub-clinical settings (i.e., in chronic smokers, non-smokers exposed to e-cigarette aerosol, and as a function of age). Thus far, these tools have been relegated to the realm of research, used as biomarkers of disease progression and therapeutic response. With proper validation, MRI-measures of vascular function may ultimately be used to complement the standard clinical workup, providing additional insight into the optimal treatment strategy and evaluation of treatment efficacy.