Arterial spin labeling perfusion cardiovascular magnetic resonance of the calf in peripheral arterial disease: cuff occlusion hyperemia vs exercise.

BACKGROUND: Assessment of calf muscle perfusion requires a physiological challenge. Exercise and cuff-occlusion hyperemia are commonly used methods, but it has been unclear if one is superior to the other. We hypothesized that post-occlusion calf muscle perfusion (Cuff) with pulsed arterial spin labeling (PASL) cardiovascular magnetic resonance (CMR) at 3 Tesla (T) would yield greater perfusion and improved reproducibility compared to exercise hyperemia in studies of peripheral arterial disease (PAD). METHODS: Exercise and Cuff cohorts were independently recruited. PAD patients had an ankle brachial index (ABI) between 0.4-0.9. Controls (NL) had no risk factors and ABI 0.9-1.4. Subjects exercised until exhaustion (15 NL-Ex, 15 PAD-Ex) or had a thigh cuff inflated for 5 minutes (12 NL-Cuff, 11 PAD-Cuff). Peak exercise and average cuff (Cuff mean ) perfusion were compared. Six participants underwent both cuff and exercise testing. Reproducibility was tested in 8 Cuff subjects (5 NL, 3 PAD). RESULTS: Controls had greater perfusion than PAD independent of stressor (NL-Ex 74 ± 21 vs. PAD-Ex 43 ± 10, p = 0.01; NL-Cuff mean 109 ± 39 vs. PAD-Cuff mean 34 ± 17 ml/min-100 g, p < 0.001). However, there was no difference between exercise and Cuff mean perfusion within groups (p > 0.6). Results were similar when the same subjects had the 2 stressors performed. Cuff mean had superior reproducibility (Cuff mean ICC 0.98 vs. Exercise ICC 0.87) and area under the receiver operating characteristic curve (Cuff mean 0.992 vs. Exercise 0.905). CONCLUSIONS: Cuff hyperemia differentiates PAD patients from controls, as does exercise stress. Cuff mean and exercise calf perfusion values are similar. Cuff occlusion hyperemia has superior reproducibility and thus may be the preferred stressor.

Reproducibility of rest and exercise stress contrast-enhanced calf perfusion magnetic resonance imaging in peripheral arterial disease.

BACKGROUND: The purpose was to determine the reproducibility and utility of rest, exercise, and perfusion reserve (PR) measures by contrast-enhanced (CE) calf perfusion magnetic resonance imaging (MRI) of the calf in normal subjects (NL) and patients with peripheral arterial disease (PAD). METHODS: Eleven PAD patients with claudication (ankle-brachial index 0.67 ±0.14) and 16 age-matched NL underwent symptom-limited CE-MRI using a pedal ergometer. Tissue perfusion and arterial input were measured at rest and peak exercise after injection of 0.1 mM/kg of gadolinium-diethylnetriamine pentaacetic acid (Gd-DTPA). Tissue function (TF) and arterial input function (AIF) measurements were made from the slope of time-intensity curves in muscle and artery, respectively, and normalized to proton density signal to correct for coil inhomogeneity. Perfusion index (PI) = TF/AIF. Perfusion reserve (PR) = exercise TF/ rest TF. Intraclass correlation coefficient (ICC) was calculated from 11 NL and 10 PAD with repeated MRI on a different day. RESULTS: Resting TF was low in NL and PAD (mean ± SD 0.25 ± 0.18 vs 0.35 ± 0.71, p = 0.59) but reproducible (ICC 0.76). Exercise TF was higher in NL than PAD (5.5 ± 3.2 vs. 3.4 ± 1.6, p = 0.04). Perfusion reserve was similar between groups and highly variable (28.6 ± 19.8 vs. 42.6 ± 41.0, p = 0.26). Exercise TF and PI were reproducible measures (ICC 0.63 and 0.60, respectively). CONCLUSION: Although rest measures are reproducible, they are quite low, do not distinguish NL from PAD, and lead to variability in perfusion reserve measures. Exercise TF and PI are the most reproducible MRI perfusion measures in PAD for use in clinical trials.

Arterial spin labeling MR imaging reproducibly measures peak-exercise calf muscle perfusion: a study in patients with peripheral arterial disease and healthy volunteers.

OBJECTIVES: This study hypothesized that arterial spin labeling (ASL) magnetic resonance (MR) imaging at 3-T would be a reliable noncontrast technique for measuring peak exercise calf muscle blood flow in both healthy volunteers and patients with peripheral arterial disease (PAD) and will discriminate between these groups. BACKGROUND: Prior work demonstrated the utility of first-pass gadolinium-enhanced calf muscle perfusion MR imaging in patients with PAD. However, patients with PAD often have advanced renal disease and cannot receive gadolinium. METHODS: PAD patients had claudication and an ankle brachial index of 0.4 to 0.9. Age-matched normal subjects (NL) had no PAD risk factors and were symptom-free with exercise. All performed supine plantar flexion exercise in a 3-T MR imaging scanner using a pedal ergometer until exhaustion or limiting symptoms and were imaged at peak exercise with 15 averaged ASL images. Peak perfusion was measured from ASL blood flow images by placing a region of interest in the calf muscle region with the greatest signal intensity. Perfusion was compared between PAD patients and NL and repeat testing was performed in 12 subjects (5 NL, 7 PAD) for assessment of reproducibility. RESULTS: Peak exercise calf perfusion of 15 NL (age: 54 ± 9 years) was higher than in 15 PAD patients (age: 64 ± 5 years, ankle brachial index: 0.70 ± 0.14) (80 ± 23 ml/min - 100 g vs. 49 ± 16 ml/min/100 g, p < 0.001). Five NL performed exercise matched to PAD patients and again demonstrated higher perfusion (84 ± 25 ml/min - 100 g, p < 0.002). As a measure of reproducibility, intraclass correlation coefficient between repeated studies was 0.87 (95% confidence interval [CI]: 0.61 to 0.96). Interobserver reproducibility was 0.96 (95% CI: 0.84 to 0.99). CONCLUSIONS: ASL is a reproducible noncontrast technique for quantifying peak exercise blood flow in calf muscle. Independent of exercise time, ASL discriminates between NL and PAD patients. This technique may prove useful for clinical trials of therapies for improving muscle perfusion, especially in patients unable to receive gadolinium.

Usefulness of cardiovascular magnetic resonance imaging of the superficial femoral artery for screening patients with diabetes mellitus for atherosclerosis.

Cardiovascular magnetic resonance (CMR) of the superficial femoral artery (SFA) allows direct and noninvasive visualization of atherosclerotic plaque burden. We examined atherosclerosis in 3 groups of patients without history or symptoms of peripheral arterial disease with varying expected burdens: those with diabetes mellitus (DM) and known coronary artery disease (CAD) (n = 24), those with DM and a high prevalence of CAD risk factors (n = 20), and controls of similar age without DM or CAD and few CAD risk factors (n = 15). We also assessed the diagnostic accuracy of this technique to differentiate among these 3 groups. T1-weighted spin-echocardiographic images were used to measure mean wall thickness (WT) and total wall volume indexed to total vessel volume. Diagnostic accuracy was assessed by area under receiver operating characteristics curve analysis. Patients with DM plus risk factors and DM plus CAD had higher mean WT (1.28 and 1.37 mm) and mean indexed wall volume (0.53 and 0.56) compared to controls (mean WT 1.16 mm and mean indexed wall volume 0.45; p <0.010 for all comparisons). Mean WT and indexed wall volume showed good diagnostic accuracy in discriminating controls from those with DM plus CAD (areas under curve 0.85 and 0.87, respectively, p <0.001), whereas only indexed wall volume discriminated DM plus risk factors from controls (area under curve 0.82, p <0.001). Neither could discriminate between DM plus risk factors and DM plus CAD. In conclusion, patients with DM plus risk factors and DM plus CAD had significantly greater atherosclerotic burden in the SFA on CMR imaging than controls of similar age, with good diagnostic accuracy in differentiating these groups. The high reproducibility and reliability of CMR of the SFA may facilitate improved assessment of atherosclerosis prevalence and progression/regression in studies of novel therapies.

Standing low-field magnetic resonance imaging appearance of normal collateral ligaments of the equine distal interphalangeal joint.

High- and low-field magnetic resonance (MR) imaging systems are available for clinical diagnosis of collateral desmopathy of the equine distal interphalangeal joint (DIJ). Knowledge of the normal appearance, size, shape,and signal variation of these ligaments on high- and low-field MR images is essential when assessing desmopathy detected by MR imaging. However, there are no descriptions of the normal features of DIJ collateral ligaments on images obtained with a standing low-field MR system. Low-field MR imaging characteristics of normal collateral ligaments of the DIJ of cadaver feet were corroborated with high-field MR imaging and histologic examination to exclude desmopathy. The size and shape of the collateral ligaments of the DIJ was similar among limbs; however, the signal pattern of the ligaments varied depending on the segment of the ligament being assessed and the MR sequence used. In limbs positioned within the magnet as recommended for clinical MR imaging, collateral ligaments of the DIJ have heterogeneous signal pattern with a peripheral region of increased signal intensity at the level of the middle phalanx that can be confused with a desmopathy.The MR imaging characteristics of normal collateral ligaments of the DIJ are related to their anatomy and fiber configuration. The results of this study support the presence of magic angle effect within the axial margin of the CL of the DIJ at the level of fiber divergence within the proximal to mid-portion of the ligament.

Low-density lipoprotein lowering does not improve calf muscle perfusion, energetics, or exercise performance in peripheral arterial disease.

OBJECTIVES: We hypothesized that low-density lipoprotein (LDL) reduction regardless of mechanism would improve calf muscle perfusion, energetics, or walking performance in peripheral arterial disease (PAD) as measured by magnetic resonance imaging and magnetic resonance spectroscopy. BACKGROUND: Statins improve cardiovascular outcome in PAD, and some studies suggest improved walking performance. METHODS: Sixty-eight patients with mild to moderate symptomatic PAD (age 65 ± 11 years; ankle-brachial index [ABI] 0.69 ± 0.14) were studied at baseline and annually for 2 years after beginning simvastatin 40 mg (n = 20) or simvastatin 40 mg/ezetimibe 10 mg (n = 18) if statin naïve, or ezetimibe 10 mg (n = 30) if taking a statin. Phosphocreatine recovery time was measured by (31)P magnetic resonance spectroscopy immediately after symptom-limited calf exercise on a 1.5-T scanner. Calf perfusion was measured using first-pass contrast-enhanced magnetic resonance imaging with 0.1 mM/kg gadolinium at peak exercise. Gadolinium-enhanced magnetic resonance angiography was graded. A 6-min walk and a standardized graded Skinner-Gardner exercise treadmill test with peak Vo(2) were performed. A repeated-measures model compared changes over time. RESULTS: LDL reduction from baseline to year 2 was greater in the simvastatin 40 mg/ezetimibe 10 mg group (116 ± 42 mg/dl to 56 ± 21 mg/dl) than in the simvastatin 40 mg group (129 ± 40 mg/dl to 90 ± 30 mg/dl, p < 0.01). LDL also decreased in the ezetimibe 10 mg group (102 ± 28 mg/dl to 79 ± 27 mg/dl, p < 0.01). Despite this, there was no difference in perfusion, metabolism, or exercise parameters between groups or over time. Resting ABI did improve over time in the ezetimibe 10 mg group and the entire study group of patients. CONCLUSIONS: Despite effective LDL reduction in PAD, neither tissue perfusion, metabolism, nor exercise parameters improved, although rest ABI did. Thus, LDL lowering does not improve calf muscle physiology or functional capacity in PAD. (Comprehensive Magnetic Resonance of Peripheral Arterial Disease; NCT00587678).

The effect of ezetimibe on peripheral arterial atherosclerosis depends upon statin use at baseline.

BACKGROUND: Both statins and ezetimibe lower LDL-C, but ezetimibe's effect on atherosclerosis is controversial. We hypothesized that lowering LDL-C cholesterol by adding ezetimibe to statin therapy would regress atherosclerosis measured by magnetic resonance imaging (MRI) in the superficial femoral artery (SFA) in peripheral arterial disease (PAD). METHODS: Atherosclerotic plaque volume was measured in the proximal 15-20 cm of the SFA in 67 PAD patients (age 63 ± 10, ABI 0.69 ± 0.14) at baseline and annually × 2. Statin-naïve patients (n=34) were randomized to simvastatin 40 mg (S, n=16) or simvastatin 40 mg+ezetimibe 10mg (S+E, n=18). Patients already on statins but with LDL-C >80 mg/dl had open-label ezetimibe 10mg added (E, n=33). Repeated measures models estimated changes in plaque parameters over time and between-group differences. RESULTS: LDL-C was lower at year 1 in S+E (67 ± 7 mg/dl) than S (91 ± 8 mg/dl, p<0.05), but similar at year 2 (68 ± 10 mg/dl vs. 83 ± 11 mg/dl, respectively). Plaque volume did not change from baseline to year 2 in either S+E (11.5 ± 1.4-10.5 ± 1.3 cm(3), p=NS) or S (11.0 ± 1.5-10.5 ± 1.4 cm(3), p=NS). In E, plaque progressed from baseline to year 2 (10.0 ± 0.8-10.8 ± 0.9, p<0.01) despite a 22% decrease in LDL-C. CONCLUSIONS: Statin initiation with or without ezetimibe in statin-naïve patients halts progression of peripheral atherosclerosis. When ezetimibe is added to patients previously on statins, peripheral atherosclerosis progressed. Thus, ezetimibe's effect on peripheral atherosclerosis may depend upon relative timing of statin therapy.

Patterns of late gadolinium enhancement in chronic hemodialysis patients.

OBJECTIVES: The aim of this work was to characterize patterns of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance imaging in a hemodialysis population at high risk for cardiovascular events. BACKGROUND: The prevalence and distribution of LGE and its relationship to left ventricular mass (LVM) and function in this population is unknown. METHODS: Chronic hemodialysis patients at high risk for cardiovascular events-age >50 years, diabetes, or known cardiovascular disease-were enrolled prior to concerns regarding nephrogenic systemic fibrosis. Cardiovascular magnetic resonance imaging was performed in 24 patients (age, 59 +/- 11 years; dialysis, 45 +/- 38 months) and included steady-state free precession cine imaging and late gadolinium-enhanced, phase-sensitive, inversion-recovery gradient echo images. Left ventricular mass, volumes, and function were calculated and indexed to body surface area. A 16-segment analysis was performed to calculate percentage of LGE, LV wall thickness, and percentage of wall thickening. RESULTS: Left ventricular ejection fraction was 48 +/- 15%, and the LV mass index was 100 +/- 52 g/m(2). Late gadolinium enhancement was observed in 79% (19 of 24) of patients in 3 distinct patterns: infarct-related (32%, 6 of 19), diffuse (37%, 7 of 19), and focal noninfarct (37%, 7 of 19). Late gadolinium enhancement constituted 15 +/- 18% of the LVM and correlated with LVM (r = 0.44, p = 0.03). A significant, inverse relationship existed between segmental LGE and the percentage of wall thickening (p > 0.0001). Excluding infarct-related segments, as end-diastolic wall thickness increased, so did LGE (p < 0.0001), and as LGE increased, the percentage of wall thickening decreased (p = 0.0012). After 23 +/- 3 months of follow-up, 1 patient had developed nephrogenic systemic fibrosis. Seven of the patients (29%) had developed a hard cardiovascular event, 5 of 19 (26%) with LGE and 2 of 5 (40%) without. CONCLUSIONS: Late gadolinium enhancement is prevalent in the hemodialysis population and its extent is related to LVM. Most cases of LGE are not infarct-related and are associated with hypertrophied, dysfunctional LV segments. Non-infarct-related LGE may signify fibrosis from LV hypertrophy and/or an infiltrative process. Further studies in this patient population will not be possible due to the risk of nephrogenic systemic fibrosis.

Can late gadolinium enhancement by cardiovascular magnetic resonance identify coronary artery disease as the etiology of new onset congestive heart failure?

BACKGROUND: New left ventricular systolic dysfunction affects 500,000 Americans and coronary artery disease (CAD) is responsible for two-thirds of cases. Identifying CAD has both prognostic and therapeutic implications. We evaluated the ability of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance imaging (CMR) to detect CAD as the etiology of recent onset congestive heart failure (CHF). METHODS: CMR and LGE were performed in 26 patients with new onset left ventricular systolic dysfunction. All patients received an x-ray angiography for identification of CAD. Patients with an acute coronary syndrome with troponin I > 1.0 ng/ml or a history of CAD were excluded. The presence and distribution of LGE was evaluated. RESULTS: Significant coronary stenoses were present in 5 of 26 patients (19%). LGE in an infarct pattern was found in 2 of the 5 patients with CAD. Of the 21 patients without CAD, 2 had midwall enhancement but none had evidence of LGE in an infarct pattern. CONCLUSIONS: When present, LGE in an infarct pattern suggests CAD as the etiology of new onset CHF. However, the absence of LGE does not exclude CAD as the underlying etiology. A small proportion of patients with a nonischemic cause of new onset CHF have LGE limited to the midwall.

Molality as a unit of measure for expressing 1H MRS brain metabolite concentrations in vivo.

Absolute concentrations of cerebral metabolite in in vivo 1H magnetic resonance spectroscopy studies (1H-MRS) are widely reported in molar units as moles per liter of tissue, or in molal units as moles per kilogram of tissue. Such measurements require external referencing or assumptions as to local water content. To reduce the scan time, avoid assumptions that may be invalid under specific pathologies, and provide a universally accessible referencing procedure, we suggest that metabolite concentrations from 1H-MRS measurements in vivo be reported in molal units as moles per kilogram of tissue water. Using internal water referencing, a two-compartment water model, a simulated brain spectrum for peak identification, and a spectroscopic bi-exponential spin-spin relaxation segmentation technique, we measured the absolute concentrations for the four common 1H brain metabolites: choline (Cho), myo-inositol (mIno), phosphocreatine + creatine (Cr), and N-acetyl-aspartate (NAA), in the hippocampal region (n = 26) and along the Sylvian fissure (n = 61) of 35 healthy adults. A stimulated echo localization method (20 ms echo time, 10 ms mixing time, 4 s repetition time) yielded metabolite concentrations, uncorrected for metabolite relaxation or contributions from macromolecule resonances, that were expectantly higher than with molar literature values. Along the Sylvian fissure the average concentrations (coefficient of variation (CV)) in mmoles/kg of tissue water were 17.6 (12%) for NAA, 14.2 (9%) for Cr, 3.6 (13%) for Cho, and 13.2 (15%) for mIno. Respective values for the hippocampal region were 15.7 (20%), 14.7 (16%), 4.6 (19%), and 17.7 (26%). The concentrations of the two regions were significantly different (p