Cardiac exercise imaging using a 3-tesla magnetic resonance-conditional pedal ergometer: Preliminary results in healthy volunteers and patients with known or suspected coronary artery disease.

BACKGROUND: Cardiac magnetic resonance imaging (CMR) remains underutilized as an exercise imaging modality, mostly because of the limited availability of MR-compatible exercise equipment. This study prospectively evaluates the clinical feasibility of a newly developed MR-conditional pedal ergometer for exercise CMR METHODS: Ten healthy volunteers (mean age 44 ± 16 years) and 11 patients (mean age 60 ± 9 years) with known or suspected coronary artery disease (CAD) underwent rest and post-exercise cinematic 3T CMR. Visual analysis of wall motion abnormalities (WMA) was rated by 2 experienced radiologists, and volumes and ejection fractions (EF) were determined. Image quality was assessed by a 4-point Likert scale for visibility of endocardial borders. RESULTS: Median subjective image quality of real-time cine at rest was 1 (interquartile range [IQR] 1-2) and 2 (IQR 2-2.5) for post-exercise real-time cine (p = 0.001). Exercise induced a significant increase in heart rate (62 [62-73] to 111 [104-143] bpm, p < 0.0001). Stroke volume and cardiac index increased from resting to post-exercise conditions (85 ± 21 to 101 ± 19 mL and 2.9 ± 0.7 to 6.6 ± 1.9 L/min/m2, respectively; both p < 0.0001), driven by a reduction in end-systolic volume (55 ± 20 to 42 ± 21 mL, p < 0.0001). Patients (2/11) with inducible regional WMA at high-resolution postexercise cine imaging revealed significant coronary artery stenosis in subsequently performed invasive coronary angiography. CONCLUSIONS: Exercise-CMR using our newly developed 3T MR-conditional pedal ergometer is clinically feasible. Imaging of both cardiac response and myocardial ischemia, triggered by dynamic stress, is rapidly conducted while the patient is near their peak heart rate.

Comparison of an oscillometric method with cardiac magnetic resonance for the analysis of aortic pulse wave velocity.

OBJECTIVES: Pulse wave velocity (PWV) is the proposed gold-standard for the assessment of aortic elastic properties. The aim of this study was to compare aortic PWV determined by a recently developed oscillometric device with cardiac magnetic resonance imaging (CMR). METHODS: PWV was assessed in 40 volunteers with two different methods. The oscillometric method (PWVOSC) is based on a transfer function from the brachial pressure waves determined by oscillometric blood pressure measurements with a common cuff (Mobil-O-Graph, I.E.M. Stolberg, Germany). CMR was used to determine aortic PWVCMR with the use of the transit time method based on phase-contrast imaging at the level of the ascending and abdominal aorta on a clinical 1.5 Tesla scanner (Siemens, Erlangen, Germany). RESULTS: The median age of the study population was 34 years (IQR: 24-55 years, 11 females). A very strong correlation was found between PWVOSC and PWVCMR (r = 0.859, p < 0.001). Mean PWVOSC was 6.7 ± 1.8 m/s and mean PWVCMR was 6.1 ± 1.8 m/s (p < 0.001). Analysis of agreement between the two measurements using Bland-Altman method showed a bias of 0.57 m/s (upper and lower limit of agreement: 2.49 m/s and -1.34 m/s). The corresponding coefficient of variation between both measurements was 15%. CONCLUSION: Aortic pulse wave velocity assessed by transformation of the brachial pressure waveform showed an acceptable agreement with the CMR-derived transit time method.

Cardiac high-energy phosphate metabolism alters with age as studied in 196 healthy males with the help of 31-phosphorus 2-dimensional chemical shift imaging.

Recently published studies have elucidated alterations of mitochondrial oxidative metabolism during ageing. The intention of the present study was to evaluate the impact of ageing on cardiac high-energy phosphate metabolism and cardiac function in healthy humans. 31-phosphorus 2-dimensional chemical shift imaging (31P 2D CSI) and echocardiography were performed in 196 healthy male volunteers divided into groups of 20 to 40 years (I, n = 43), 40 to 60 years (II, n = 123) and >60 years (III, n = 27) of age. Left ventricular PCr/ß-ATP ratio, myocardial mass (MM), ejection fraction and E/A ratio were assessed. Mean PCr/ß-ATP ratios were significantly different among the three groups of volunteers (I, 2.10 ± 0.37; II, 1.77 ± 0.37; III, 1.45 ± 0.28; all p<0.001). PCr/ß-ATP ratios were inversely related to age (r(2)  =  -0.25; p<0.001) with a decrease from 2.65 by 0.02 per year of ageing. PCr/ß-ATP ratios further correlated with MM (r =  -0.371; p<0.001) and E/A ratios (r = 0.213; p<0.02). Moreover, E/A ratios (r =  -0.502, p<0.001), MM (r = 0.304, p<0.001), glucose-levels (r = 0.157, p<0.05) and systolic blood pressure (r = 0.224, p<0.005) showed significant correlations with age. The ejection fraction did not significantly differ between the groups. This study shows that cardiac PCr/ß-ATP ratios decrease moderately with age indicating an impairment of mitochondrial oxidative metabolism due to age. Furthermore, MM increases, and E/A ratio decreases with age. Both correlate with left-ventricular PCr/ß-ATP ratios. The findings of the present study confirm numerous experimental studies showing an impairment of cardiac mitochondrial function with age.

White matter changes in patients with friedreich ataxia after treatment with erythropoietin.

BACKGROUND AND PURPOSE: Erythropoietin (EPO) has received growing attention because of its neuroregenerative properties. Preclinical and clinical evidence supports its therapeutic potential in brain conditions like stroke, multiple sclerosis, and schizophrenia. Also, in Friedreich ataxia, clinical improvement after EPO therapy was shown. The aim of this study was to assess possible therapy-associated brain white matter changes in these patients. METHODS: Nine patients with Friedreich ataxia underwent Diffusion Tensor Imaging (DTI) before and after EPO treatment. Tract-based spatial statistics was used for longitudinal comparison. RESULTS: We detected widespread longitudinal increase in fractional anisotropy and axial diffusivity (D||) in cerebral hemispheres bilaterally (P < .05, corrected), while no changes were observed within the cerebellum, medulla oblongata, and pons. CONCLUSIONS: To the best of our knowledge, this is the first DTI study to investigate the effects of EPO in a neurodegenerative disease. Anatomically, the diffusivity changes appear disease unspecific, and their biological underpinnings deserve further study.

Radial diffusivity in the cerebellar peduncles correlates with clinical severity in Friedreich ataxia.

Friedreich ataxia (FRDA) is a common inherited ataxia, caused by an expanded GAA repeat sequence in the Frataxin (FXN) gene. The proprioceptive system, which enters the cerebellum through the cerebellar peduncles, is a primary focus of pathology. In this study, we investigate the relationship of clinical and genetic data with diffusion-tensor imaging (DTI) indices reflecting white matter integrity of the cerebellar peduncles. Nine FRDA patients underwent DTI. After between-subject registration using tract-based spatial statistics, a white matter atlas was used for computing average values of DTI indices in the regions of interest. These were the inferior, middle and superior cerebellar peduncles (ICP, MCP, SCP). For Bonferroni correction, significance threshold was set to p < 0.0056. We found that radial diffusivity (D(⊥)) within the ICP significantly correlated with scores on the Friedreich Ataxia Rating Scale (FARS, Spearman's ρ = 0.883, p = 0.0016, all two-sided) and, at trend level, with number of trinucleotide repeats (ρ = 0.812, p = 0.008). D(⊥) in the SCP correlated with scores on the Scale for the Assessment and Rating of Ataxia (SARA, ρ = 0.867, p = 0.0025). These findings support the role of DTI, and especially D(⊥), as an informative biomarker in FRDA.

Potential of advanced MR imaging techniques in the differential diagnosis of parkinsonism.

The clinical differentiation of parkinsonian syndromes remains challenging not only for neurologists but also for movement disorder specialists. Conventional magnetic resonance imaging (cMRI) with the visual assessment of T2- and T1-weighted imaging as well as different advanced MRI techniques offer objective measures, which may be a useful tool in the diagnostic work-up of Parkinson's disease and atypical parkinsonian disorders (APDs). In clinical practice, cMRI is a well-established method for the exclusion of symptomatic parkinsonism due to other pathologies. Over the past two decades, abnormalities in the basal ganglia and infratentorial structures have been shown especially in APDs not only by cMRI but also by different advanced MRI techniques, including methods to assess regional cerebral atrophy quantitatively such as magnetic resonance volumetry, proton magnetic resonance spectroscopy, diffusion-weighted imaging, and magnetization transfer imaging. This article aims to review recent research findings on the role of advanced MRI techniques in the differential diagnosis of neurodegenerative parkinsonian disorders.

Quantification of blood flow velocity in stenosed arteries by the use of finite elements: an observer-independent noninvasive method.

Interventions for peripheral arterial disease should be designed to treat a physiological rather than an anatomic defect. Thus, for vascular surgeons, functional information about stenoses is as important as the anatomic one. In case of finding a stenosis by the use of magnetic resonance angiography, it would be a matter of particular interest to derive automatically and directly objective information about the hemodynamic influence on blood flow, caused by patient-specific stenoses. We developed a methodology to noninvasively perform numerical simulations of a patient's hemodynamic state on the basis of magnetic resonance images and by the means of the finite element method. We performed patient-specific three-dimensional simulation studies of the increase in systolic blood flow velocity due to stenoses using the commercial computational fluid dynamic software package FIDAP 8.52. The generation of a mesh defining the flow domain with a stenosis and some simulation results are shown.

Inter- and intra-rater reproducibility of semiautomatic determination of volume parameters in cardiac magnetic resonance imaging.

PURPOSE: The purpose of this study was to evaluate inter- and intra-rater reproducibility in volume assessment using cardiac magnetic resonance imaging (CMRI). METHODS: Twenty-five healthy volunteers and 106 patients were included into this retrospective study and received CMRI. The patients were divided in three groups (group I, 80 patients with arrhythmia; group II, 20 patients with cardiomyopathy; group III, 6 patients after correction of septum defects). Therefore, the images were semiautomatically segmented by an experienced and an unexperienced radiologists. The analysis of end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV) as well as ejection fraction (EF) and myocardial mass (MM) were performed twice by an experienced and an unexperienced radiologists. The intra-class correlation coefficients (ICC) were determined for the evaluation of inter- and intra-rater variance. RESULTS: The intra-rater reproducibility for determination of EF, ESV, EDV and MM was excellent with ICCs ranging from 0.88 to 0.99 (all p<0.001). The inter-observer reproducibility for these parameters was also excellent with ICCs ranging from 0.91 to 0.98 (all p<0.001). The assessment of the SV showed an excellent intra-rater agreement with ICCs of 0.96 and 0.92 (both p<0.001), but only a moderate ICC for the inter-rater reproducibility (0.54, p<0.001). CONCLUSIONS: Our study shows that assessment of cardiac volumes can be performed on CMRIs with an excellent reproducibility by both experienced and unexperienced investigators.

Phosphorus-31 two-dimensional chemical shift imaging in the myocardium of patients with late onset of Friedreich ataxia.

PURPOSE: Friedreich ataxia (FRDA) is characterized by GAA expansions in the intron 1 of the frataxin gene correlating with disease onset and progression as well as cardiac affection. Accordingly, FRDA patients with early disease onset show a clear impairment of mitochondrial function in the myocardium. The purpose of this study was to investigate cardiac function and high-energy phosphate metabolism in FRDA patients with late disease onset. PROCEDURES: Using a 1.5 T magnetic resonance scanner, cardiac phosphorus-31 two-dimensional chemical shift imaging was performed in ten patients (seven male, three female) with a late onset of FRDA and in 35 healthy, male controls. Ejection faction (EF) and interventricular septum thickness (IST) were determined by echocardiography. RESULTS: The differences in left ventricular phosphocreatine (PCr) to beta-adenosine triphosphate (beta-ATP) ratios between both groups were not significant. FRDA patients had increased ISTs (10.8+/-1.6 vs. 9.7+/-0.9 mm; p=0.048), which correlated significantly with the left ventricular PCr to beta-ATP ratios (r= -0.644; p=0.04), and decreased EFs (52.24+/-7.72% vs. 64.09+/-4.25%; p=0.001) compared to normal controls. CONCLUSIONS: In contrast to FRDA patients with early disease onset, our patients collective exhibited a normal, probably compensated cardiac mitochondrial function, whereby IST and EF were mildly altered.

Diffusion weighted imaging best discriminates PD from MSA-P: A comparison with tilt table testing and heart MIBG scintigraphy.

Both diffusion weighted magnetic resonance imaging (DWI) of the basal ganglia and meta-iodobenzylguanidin (MIBG) scintigraphy of the heart have been reported useful in the differential diagnosis of patients with Parkinson's disease (PD) vs. the parkinson variant of multiple system atrophy (MSA-P). Their diagnostic value, however, has never been directly compared in patients with parkinsonism and autonomic dysfunction. We have studied 9 patients with PD and 9 patients with MSA-P matched for age and disease severity. Regional trace of the diffusion tensor values were determined in the putamina. Cardiac MIBG uptake was quantified by comparing regions of interest over heart and mediastinum Heart/Mediastinum (H/M) ratio. Furthermore, all patients underwent tilt testing. PD patients showed significantly lower H/M ratios than normal controls; however, there was considerable overlap between the two patient groups. We did not detect any significant differences of blood pressure response to passive tilt between the two patient groups. Sensitivity of MIBG scintigraphy versus DWI for the differentiation of MSA-P from PD was 55.6% vs. 100%, specificity 88.8% vs. 100%, and area under the curve 0.802 vs. 1.000. Our data suggest that DWI is superior to both tilt table testing and MIBG scintigraphy in the differential diagnosis of PD versus MSA-P.

High-energy phosphate metabolism in the calf muscle of healthy humans during incremental calf exercise with and without moderate cuff stenosis.

It is known that the relevance of a peripheral stenosis for muscle function increases with exercise. Our intention was to investigate the impact of a moderate cuff stenosis (CS) at 120 mmHg of the superficial femoral artery on high-energy phosphate (HEP) metabolism during isotonic, incremental calf exercise. Serial phosphorus 31 magnetic resonance spectroscopy (31P MRS) and velocity-encoded phase-contrast MR imaging (VEPC MRI) were carried out in each leg of ten healthy male volunteers. Each leg underwent four increments of calf exercise (2, 3, 4 and 5 W) followed by recovery during separate exercise sessions with and without a CS at 120 mmHg. The serial 31P MRS measurements had a time resolution of 10 s. VEPC MRI was performed at the end of each increment during separate sessions. During all increments, we detected significant differences (P < 0.05) in the phosphocreatine (PCr) time constants and the amount of PCr hydrolysis between the sessions without and with CS. Regarding the time courses of the PCr, inorganic phosphate (Pi) and pH level, we observed significant differences (P < 0.002) during exercise and recovery. During both conditions, the end-increment PCr levels as well as blood flow correlated significantly with the mechanical power. The PCr time constants during exercise significantly correlated with the intramuscular pH, but not with blood flow or mechanical power. However, the PCr recovery time constants correlated significantly with blood flow and end-exercise pH. Our study shows that reduction of blood flow due to a peripheral stenosis results in a prolongation of PCr time constants, decreased PCr and pH level as well as increased Pi level during exercise. We believe that 31P MRS during incremental exercise might provide additional information for assessing the relevance of a peripheral stenosis and its impact on muscle function.

High-energy phosphate metabolism during calf ergometry in patients with isolated aorto-iliac artery stenoses.

OBJECTIVES: Patients with peripheral arterial disease (PAD) and aorto-iliac atherosclerotic lesions suffer from a broad range of complaints, such as pain at the hip, the thigh, and calf claudication. The purpose of this study was to investigate the high-energy metabolism in the calf muscle of patients with PAD with isolated aorto-iliac stenoses during incremental plantar flexion exercise. MATERIALS AND METHODS: Using a 1.5 T whole-body magnetic resonance (MR) scanner, 12 patients with PAD with uni- or bilateral aorto-iliac atherosclerotic lesions and 10 healthy male controls underwent serial phosphor-31 MR spectroscopy during incremental exercise at 2, 3, 4, and 5 W. The phosphocreatine (PCr) time constants were calculated for each increment and recovery using a monoexponential model. In the patient group, the run-off resistance was determined on MR angiograms. In both the patients and the controls, the ankle brachial pressure index was measured. RESULTS: The diseased legs exhibited significantly increased PCr time constants during the second and the third workload increment at 3 and 4 W, but not during the first increment at 2 W and recovery compared with normal controls. Only 3 diseased legs succeeded the last increment at 5 W. We detected significant correlations between the ankle brachial pressure index scores and the PCr time constants when including both the diseased and the control legs. The diseased legs showed a significant correlation with the run-off resistance only during the first increment. CONCLUSIONS: Our study shows that the impairment of muscle metabolism, expressed by prolonged PCr time constants, occurs with greater work intensities in patients with aorto-iliac disease compared with patients with multisegmental PAD, as recently published, whereas our patients collective exhibited normal PCr recovery time constants. Our findings may help to understand variability of clinical symptoms in aorto-iliac PAD.

Topography of dopamine transporter availability in progressive supranuclear palsy: a voxelwise [123I]beta-CIT SPECT analysis.

BACKGROUND: Dopaminergic loss can be visualized by means of iodine I 123-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT) single-photon emission computed tomography (SPECT) in several neurodegenerative parkinsonian disorders. Most previous SPECT studies have adopted region-of-interest methods for analysis, which are subjective and operator dependent. OBJECTIVE: To objectively localize the cerebral dopamine transporter status in the early stages of progressive supranuclear palsy (PSP). DESIGN: Prospective study. SETTING: Parkinson disease outpatient clinic. PATIENTS: Fourteen patients with PSP, 17 with Parkinson disease (PD), 15 with Parkinson-variant multiple-system atrophy (MSA-P), and 13 healthy control subjects, matched for age and disease duration. INTERVENTIONS: Statistical parametric mapping applied to [(123)I]beta-CIT SPECT. MAIN OUTCOME MEASURES: Differences in [(123)I]beta-CIT uptake. RESULTS: All patients with the different parkinsonian disorders showed a significant decrease in striatal [(123)I]beta-CIT uptake without any overlap with the control group. In patients with MSA-P and PSP, an additional reduction in brainstem [(123)I]beta-CIT signal compared with controls and patients with PD was identified with statistical parametric mapping. Midbrain [(123)I]beta-CIT uptake discriminated atypical parkinsonian disorders from PD with an overall correct classification of 91.3%. On the other hand, [(123)I]beta-CIT SPECT failed to discriminate PSP and MSA-P. CONCLUSION: By applying statistical parametric mapping to [(123)I]beta-CIT SPECT images of patients with PSP, a widespread decline of monoaminergic transporter availability including the striatum and brainstem was localized in PSP, discriminating patients with PSP from patients with PD, but not from those with MSA-P. Quantification of midbrain dopamine transporter signal may therefore enhance the utility of SPECT imaging in the differential diagnosis of patients with parkinsonism.

High-energy phosphate metabolism during incremental calf exercise in patients with unilaterally symptomatic peripheral arterial disease measured by phosphor 31 magnetic resonance spectroscopy.

BACKGROUND: The treadmill exercise test is the most important examination of the functional ability of patients with intermittent claudication or leg pain during exercise, but it does not provide any metabolic information in the calf muscle. The purpose of this study was to investigate the high-energy metabolism in the calf muscle during incremental progressive plantar flexion exercise of a selected peripheral arterial disease (PAD) patient group. METHODS: Using a 1.5-T whole-body magnetic resonance scanner, 17 male patients with PAD who had 1 symptomatic and 1 asymptomatic leg and 9 healthy male controls underwent serial phosphor 31 (31P) magnetic resonance spectroscopy during incremental exercise at 2, 3, 4, and 5 W. Furthermore, magnetic resonance angiography was performed, and the ankle-brachial pressure index was determined in the patient group. The runoff resistance (ROR) was separately assessed in each patient's leg. RESULTS: The symptomatic legs exhibited significantly increased phosphocreatine (PCr) time constants during the first three workload increments (2-4 W) and the recovery phase compared with the asymptomatic legs and the normal controls. Only two symptomatic legs reached the last increment at 5 W. Compared with the normal controls, the asymptomatic legs showed significantly increased PCr time constants only at 5 W. In the patient group, we detected significant correlations between the PCr time constants and the ROR, as well as the ankle-brachial pressure index. Moreover, the symptomatic legs presented significantly lower PCr levels and pH values at the end of exercise compared with the asymptomatic and control legs. CONCLUSIONS: Our study shows that muscle function in PAD patients can be objectively quantified with the help of 31P magnetic resonance spectroscopy and correlates significantly with hemodynamic parameters such as ROR and ankle-brachial pressure index. Consequently, 31P magnetic resonance spectroscopy seems to be a useful method to monitor the muscle function of PAD patients for evaluation of established therapies or new therapeutic strategies during research trials.

Diffusion-weighted imaging in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder that results from an expanded trinucleotide (CAG) repeat on the huntingtin gene. Neurodegeneration in HD affects most prominently the basal ganglia. Therefore, diffusivity was obtained in the basal ganglia and thalamus of 29 patients with early HD and 27 healthy volunteers by means of the trace of the diffusion tensor (Trace(D)). Putaminal, caudate, pallidal, and thalamic Trace(D) values were increased in patients with HD compared with controls. Increased diffusivity in the putamen and caudate nucleus correlated with global functional impairment, CAG repeat length, as well as bicaudate ratio. Diffusion-weighted imaging appears to be a promising surrogate marker for disease severity in HD. Sensitivity to change remains to be established longitudinally.

Topography of putaminal degeneration in multiple system atrophy: a diffusion magnetic resonance study.

There is neuropathologic evidence that, in early stages of the Parkinson variant of multiple system atrophy (MSA-P), the putamen shows a distinct topographical pathology affecting predominantly the dorsolateral and caudal regions while leaving the rostral to midparts almost intact. We investigated the topographic profile of putaminal degeneration in MSA-P patients in vivo by means of diffusion-weighted imaging (DWI), which has been shown to reveal abnormalities in the basal ganglia of patients with MSA-P compared to patients with PD and healthy controls. For this purpose, regional trace of the diffusion tensor (rTrace(D)) values were determined in the entire, anterior, and posterior putamen in 15 patients with probable MSA-P, in 20 patients with PD, and in 11 healthy volunteers matched for age and disease duration. MSA-P patients had significantly higher rTrace(D) values in entire, anterior, and posterior putamen compared to both controls and PD patients. Trace(D) values were significantly higher in the posterior compared to the anterior putamen in the MSA-P group. There were no significant differences between posterior and anterior putamen in both the control and PD group. Our study demonstrates prominent involvement of the posterior putamen in early disease stages of MSA-P in vivo by assessing putaminal diffusivity with the help of DWI.

Progression of putaminal degeneration in multiple system atrophy: a serial diffusion MR study.

By using diffusion-weighted imaging (DWI), we have recently shown abnormal diffusivity in the putamen of patients with the Parkinson variant of multiple system atrophy (MSA-P) which also correlated with disease severity, indicating the capability of putaminal diffusivity to serve as a marker for disease progression. We therefore performed a serial DWI study in 10 patients with MSA-P compared to 10 patients with Parkinson's disease (PD) to evaluate the dynamic evolution of diffusion properties in the basal ganglia including putamen, caudate nucleus and globus pallidum by means of the trace of the diffusion tensor (Trace(D)). For comparison, we have also analyzed the frequency and semiquantitative grading of MSA-P-related structural changes on conventional MRI including putaminal atrophy, lateral hyperintense margination of the putamen and putaminal signal hypointensity relative to the globus pallidum on T2 MR images. None of the Trace(D) values in the basal ganglia regions in the PD group changed significantly at follow-up compared to baseline. In MSA-P, a significant increase of the Trace(D) was found in the putamen, which correlated with motor progression as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). No significant change of any of the abnormal putaminal findings on routine MRI was obtained. We suggest that abnormal diffusivity in the putamen is sensitive to change over time in MSA-P and correlates with motor progression indicating that DWI may serve to monitor disease progression in MSA-P in an objective and quantitative manner.