Alois M. Sprinkart

Acute Myocarditis: Multiparametric Cardiac MR Imaging

PURPOSE To evaluate the diagnostic value of cardiac magnetic resonance (MR) imaging at 3 T in patients suspected of having acute myocarditis by using a multiparametric cardiac MR imaging approach including T1 relaxation time as an additional tool for tissue characterization. MATERIALS AND METHODS Ethics commission approval was obtained for this prospective study, and written informed consent was obtained from all subjects. Twenty four patients with acute myocarditis (mean age ± standard deviation, 34.7 years ± 15.1; 75% men) and 42 control subjects (mean age, 38.7 years ± 10.2; 64% men) were included. Cardiac MR imaging approaches included relative T2 short tau inversion-recovery signal intensity ratio (T2 ratio), early gadolinium enhancement ratio, late gadolinium enhancement, native T1 relaxation times, and extracellular volume fraction. Receiver operating characteristic analysis was performed to compare diagnostic performance. The reference standard was the clinical evidence for acute myocarditis. RESULTS Native T1 relaxation times were significantly longer in patients with acute myocarditis than in control subjects (1185.3 msec ± 49.3 vs 1089.1 msec ± 44.9, respectively; P < .001). Areas under the curve of native T1 relaxation times (0.94) were higher compared with those of other cardiac MR parameters (late gadolinium enhancement, 0.90; T2 ratio, 0.79; extracellular volume fraction, 0.71; early gadolinium enhancement ratio, 0.63; P = .390, .018, .002, and < .001, respectively). Sensitivity (92%), specificity (91%), and diagnostic accuracy (91%) for native T1 relaxation times (cutoff, 1140 msec) were equivalent compared with those of the established combined Lake Louise criteria (sensitivity, 92%; specificity, 80%; diagnostic accuracy, 85%). CONCLUSION Diagnostic performance with native T1 mapping was superior to that with T2 ratio and early gadolinium enhancement ratio, and specificity was higher with native T1 mapping than that with Lake Louise criteria. This study underlines the potential of native T1 relaxation times to complement current cardiac MR approaches in patients suspected of having acute myocarditis.

Diffusion-weighted magnetic resonance imaging of the pancreas: diagnostic benefit from an intravoxel incoherent motion model-based 3 b-value analysis.

ObjectivesThe objective of this study was to evaluate the diagnostic benefit of an intravoxel incoherent motion (IVIM) model–based characterization of pancreatic masses from diffusion-weighted imaging (DWI) with 3 b values. Materials and MethodsThis retrospective study had an approval from the institutional review board, and informed patient consent was waived. The 1.5-T DWI data of 42 patients with or without pancreatic disease, acquired by a respiratory-gated spin-echo echo-planar imaging sequence with 3 b values (0, 50, 800 s/mm2), were retrospectively analyzed. The IVIM-related parameters D′, which is the apparent diffusion coefficient [ADC(50,800)], and f′, as well as ADC(0,50), and conventional ADC(0,800) were calculated voxelwise. Regions of interest were analyzed in pancreatic adenocarcinomas (CAs, n = 12), neuroendocrine pancreatic tumors (NETs, n = 9), and chronic pancreatitis (CPs, n = 11), not affected tissue of each pathologic group, and in the head, body, and tail of the healthy pancreas (n = 10). ResultsBy ADC(0,800) and D′, CAs could hardly be distinguished from neuroendocrine pancreatic tumors and chronic pancreatitis. However, CAs revealed very low ADC(0,50) and f′ values, which differed significantly from all other groups. In the healthy pancreas, ADC(0,800) and D′ values were significantly higher for the head than for the body and tail, but no significant differences were found for ADC(0,50) and f′. ConclusionsThe determination of IVIM-based microcirculation-sensitive parameter maps from DWI with 3 b values significantly improved the discrimination of CAs from NETs, CPs, and the healthy tissue.

Incremental value of quantitative CMR including parametric mapping for the diagnosis of acute myocarditis

AIM Cardiac magnetic resonance (CMR) can visualize inflammatory tissue changes in acute myocarditis. Several quantitative image-derived parameters have been described to enhance the diagnostic value of CMR, but no direct comparison of these techniques is available. METHODS AND RESULTS A total of 34 patients with suspected acute myocarditis and 50 control subjects underwent CMR. CMR protocol included quantitative assessment of T1 relaxation times using modified Look-Locker inversion recovery (MOLLI) and shortened MOLLI (ShMOLLI) acquisition schemes, extracellular volume fraction (ECV), T2 relaxation times, and longitudinal strain. Established Lake-Louise criteria (LLC) consisting of T2-weighted signal intensity ratio (T2-ratio), early gadolinium enhancement ratio (EGEr), and late gadolinium enhancement (LGE) were assessed. Receiver operating characteristics analysis was performed to compare diagnostic performance. Areas under the curve of native T1 (MOLLI: 0.95; ShMOLLI: 0.92) and T2 relaxation times (0.92) were higher compared with those of the other CMR parameters (T2-ratio: 0.71, EGEr: 0.71, LGE: 0.87, LLC: 0.90, ECV MOLLI: 0.77, ECV ShMOLLI: 0.80, longitudinal strain: 0.83). Combined with LGE, each native mapping technique outperformed the diagnostic performance of LLC (P < 0.01, respectively). A combination of native parameters (T1, T2, and longitudinal strain) significantly increased the diagnostic performance of CMR compared with LLC without need of contrast media application (0.99 vs. 0.90; P = 0.008). CONCLUSION In patients suspected of having acute myocarditis, diagnostic performance of CMR can be improved by implementation of quantitative CMR parameters. Especially, native mapping techniques have the potential to replace current LLC. CLINICALTRIALS. GOV NUMBER NCT02299856.

N-Acetylaspartylglutamate (NAAG) and N-Acetylaspartate (NAA) in Patients With Schizophrenia

UNLABELLED BACKGROUND : Imbalance of glutamatergic neurotransmission has been proposed as a key mechanism underlying symptoms of schizophrenia. The neuropetide N-acetylaspartylglutamate (NAAG) modulates glutamate release. NAAG provides a component of the proton magnetic resonance spectrum (1H-MRS) in humans. The signal of NAAG, however, largely overlaps with its precursor and degrading product N-acetylaspartate (NAA) that by itself does not act in glutamatergic neurotransmission. METHODS We quantified NAAG and NAA separately from the 1H-MRS signal in 20 patients with schizophrenia and 20 healthy comparison subjects on a 3.0 Tesla MR scanner. The 1H-MRS voxels were positioned in the anterior cingulate cortex (ACC) and in the left frontal lobe. Psychopathological symptoms and cognitive performance were assessed. RESULTS In the ACC, the ratio NAAG/NAA was increased (P = .041) and NAAG was increased at a trend level (P = .066) in patients, while NAA was reduced (P = .030). NAA correlated with attention performance in patients (r = .64, P = .005) in the ACC. There was no group difference of NAAG, NAA, or NAAG/NAA in the frontal lobe but an inverse correlation of NAAG with negatives symptoms (Positive and Negative Symptoms Scale [PANSS] negative, r = -.58, P = .018) and with the total symptom score (PANSS total, r = -.50, P = .049). In addition, there was a positive correlation of frontal lobe NAAG (r = .53, P = .035) and NAAG/NAA (r = .54, P = .030) with episodic memory in patients. CONCLUSIONS In this study, we present the first in vivo evidence for altered NAAG concentration in patients with schizophrenia.

Dynamic and simultaneous MR measurement of R1 and R2* changes during respiratory challenges for the assessment of blood and tissue oxygenation

This work presents a novel method for the rapid and simultaneous measurement of R1 and R2* relaxation rates. It is based on a dynamic short repetition time steady‐state spoiled multigradient‐echo sequence and baseline R1 and B1 measurements. The accuracy of the approach was evaluated in simulations and a phantom experiment. The sensitivity and specificity of the method were demonstrated in one volunteer and in four patients with intracranial tumors during carbogen inhalation. We utilized (ΔR2*, ΔR1) scatter plots to analyze the multiparametric response amplitude of each voxel within an area of interest. In normal tissue R2* decreased and R1 increased moderately in response to the elevated blood and tissue oxygenation. A strong negative ΔR2* and ΔR1 response was observed in veins and some tumor areas. Moderate positive ΔR2* and ΔR1 response amplitudes were found in fluid‐rich tissue as in cerebrospinal fluid, peritumoral edema, and necrotic areas. The multiparametric approach was shown to increase the specificity and sensitivity of oxygen‐enhanced MRI compared to measuring ΔR2* or ΔR1 alone. It is thus expected to provide an optimal tool for the identification of tissue areas with low oxygenation, e.g., in tumors with compromised oxygen supply. Magn Reson Med, 2013.

Intensity-modulated radiotherapy of the prostate: Dynamic ADC monitoring by DWI at 3.0 T

BACKGROUND AND PURPOSE Diffusion weighted imaging (DWI) as a functional MR technique allows for both qualitative and quantitative assessment of tumour cellularity and changes during therapy. The objective of this study was to evaluate changes of apparent diffusion coefficient (ADC) in biopsy proven prostate cancer (PCa) under intensity modulated radiotherapy (IMRT) at 3T. MATERIAL & METHODS Thirteen patients with biopsy proven PCa treated with intensity modulated external beam radiotherapy (IMRT) underwent four standardized MR examinations after approval of the local institutional review board. These included DWI at 3T on a strict time table: before, in between, directly after (between 1 and 4 days after the last radiation), as well as 3 months after IMRT. Quantitative analysis of two different ADCs, - the ADC(0,800) and the ADC(50,800), was performed dynamically over 4 time points in PCa, gluteal muscle and healthy prostate tissue. RESULTS In PCa, a significant increase of ADC(0,800)/ADC(50,800) values was measured under IMRT by about 16%/15% (P=0.00008/0.00017), 21%/21% (P=0.00006/0.00030), and 33%/34% (P=0.00004/0.00002) at the three time points compared to initial value. Healthy prostate tissue did not show any significant increase. CONCLUSION DWI is suitable as a biomarker for radiation therapy response of PCa by allowing the dynamic monitoring of treatment effectiveness.

Comprehensive Cardiac Magnetic Resonance for Short‐Term Follow‐Up in Acute Myocarditis

Background Cardiac magnetic resonance (CMR) can detect inflammatory myocardial alterations in patients suspected of having acute myocarditis. There is limited information regarding the degree of normalization of CMR parameters during the course of the disease and the time window during which quantitative CMR should be most reasonably implemented for diagnostic work‐up. Methods and Results Twenty‐four patients with suspected acute myocarditis and 45 control subjects underwent CMR. Initial CMR was performed 2.6±1.9 days after admission. Myocarditis patients underwent CMR follow‐up after 2.4±0.6, 5.5±1.3, and 16.2±9.9 weeks. The CMR protocol included assessment of standard Lake Louise criteria, T1 relaxation times, extracellular volume fraction, and T2 relaxation times. Group differences between myocarditis patients and control subjects were highest in the acute stage of the disease (P<0.001 for all parameters). There was a significant and consistent decrease in all inflammatory CMR parameters over the course of the disease (P<0.01 for all parameters). Myocardial T1 and T2 relaxation times—indicative of myocardial edema—were the only single parameters showing significant differences between myocarditis patients and control subjects on 5.5±1.3‐week follow‐up (T1: 986.5±44.4 ms versus 965.1±28.1 ms, P=0.022; T2: 55.5±3.2 ms versus 52.6±2.6 ms; P=0.001). Conclusions In patients with acute myocarditis, CMR markers of myocardial inflammation demonstrated a rapid and continuous decrease over several follow‐up examinations. CMR diagnosis of myocarditis should therefore be attempted at an early stage of the disease. Myocardial T1 and T2 relaxation times were the only parameters of active inflammation/edema that could discriminate between myocarditis patients and control subjects even at a convalescent stage of the disease.

Cardiac Magnetic Resonance Reveals Signs of Subclinical Myocardial Inflammation in Asymptomatic HIV-Infected Patients.

Background—People living with chronic HIV infection are at an increased risk for cardiovascular disease. With this study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients by a comprehensive cardiac magnetic resonance (CMR) approach. Methods and Results—Asymptomatic patients with chronic HIV infection undergoing combination antiretroviral therapy (n=28) and control subjects (n=22) underwent CMR. HIV-infected patients were successfully controlled for the disease with a consistent plasma viremia of <200 copies/mL (mean CD4+-cell count, 475.1±307.9 cells/&mgr;L). CMR protocol allowed for the determination of cardiac function, myocardial inflammation, myocardial fibrosis, aortic stiffness, and pericardial fat volume. When compared with healthy controls, HIV-infected patients showed alterations in left ventricular function as demonstrated by a lower ejection fraction (60.9±7.1% versus 65.2±5.5%; P=0.023) and lower global peak systolic longitudinal and circumferential strain values (longitudinal strain, −17.7±3.4% versus −20.2±3.2%, circumferential strain, −21.2±4.6% versus −24.7±5.1%; P<0.001, respectively). CMR parameters indicating myocardial inflammation were elevated in HIV-infected patients (native T1 relaxation times, 1128.3±53.4 ms versus 1086.5±54.5 ms; P=0.009; relative T2 signal intensity ratio, 1.6±0.3 versus 1.4±0.3; P=0.046; early gadolinium enhancement ratio, 3.1±1.2 versus 2.1±0.6; P=0.003). Myocardial fibrosis, predominantly at the subepicardium of the midventricular and basal inferolateral wall, was prevalent in 82.1% of HIV-infected patients, but only in 27.3% of healthy controls (P<0.001). Conclusions—Comprehensive CMR revealed a high burden of cardiovascular disease in asymptomatic HIV-infected patients. Subclinical myocardial inflammation as detected by CMR may be a potential precursor of the increased cardiovascular morbidity and mortality observed in patients with chronic HIV infection.

Comparison of magnetic resonance feature tracking with harmonic phase imaging analysis (CSPAMM) for assessment of global and regional diastolic function.

AIMS Complex post-processing is required for strain-derived assessment of diastolic dysfunction (DD) using CMR-tagging (TAG). Feature-tracking (FT), allows for rapid systolic strain assessment using conventional steady-state free precession (SSFP)-Cine sequences. Aim of this study was to investigate whether FT may be employed for the clinically applicable quantification of DD. METHODS AND RESULTS 40 individuals (20 patients with DD I-III°, 20 controls) were investigated. CSPAMM and SSFP-Cine sequences were acquired in identical short-axis locations. Global and regional early diastolic strain rate (EDSR), peak diastolic strain rate (PDSR), twist, untwist and torsion were calculated from tagged and SSFP-Cine datasets. DD indices were compared, intra- as well inter-observer variability assessed. RESULTS for global EDSR correlated strongly (r=0.94), revealed good agreement and no significant differences between both methods. Correlation for regional EDSR was lower, results differed significantly in the anterior wall (p<0.05). Correlation for PDSR was moderate (r=0.63), results in the healthy control group differed significantly (p<0.05). FT derived rotational indices correlated poorly with TAG (twist: r=0.28; untwist: r=0.02; torsion: r=0.26), subgroup analysis revealed significant differences (p<0.05). Intra- and inter-observer variability for FT derived global EDSR and PDSR were comparable to TAG, but significantly higher for regional EDSR and rotational indices. CONCLUSION FT derived global EDSR allows for rapid clinical determination of diastolic dysfunction, revealing good agreement with TAG and low intra- as well as interobserver variability. However, TAG analysis not only yields higher accuracy and reproducibility of global- and regional diastolic strain, but also delivers reliable information about diastolic rotational and untwisting dynamics.

Left Ventricular Myocardial Fibrosis, Atrophy, and Impaired Contractility in Patients With Pulmonary Arterial Hypertension and a Preserved Left Ventricular Function: A Cardiac Magnetic Resonance Study.

Purpose: Using a cardiac magnetic resonance (CMR) approach we investigated left ventricular (LV) myocardial changes associated with pulmonary arterial hypertension (PAH) by strain analysis and mapping techniques. Materials and Methods: Seventeen patients with PAH (9 men; mean age, 64.2±13.6 y) and 20 controls (10 men, 63.2±10.5 y) were examined using CMR at 1.5 T. Native LV T1-relaxation times (T1) and extracellular volume fraction (ECV) were assessed using a MOLLI sequence, T2-relaxation times (T2) by means of a gradient spin-echo sequence, and LV longitudinal strain (LVS) and right ventricular (RV) longitudinal strain (RVS) by means of CMR feature tracking. The hematocrit and serum levels of pro-Brain Natriuretic Peptide were determined on the day of the CMR examination. Pulmonary arterial pressure and 6-minute walking distance were assessed as part of the clinical evaluation. Results: T1 and ECV were higher (1048.5±46.6 vs. 968.3±22.9 ms and 32.4%±5.7% vs. 28.4%±3.8%; P<0.05) and LVS was lower in patients with PAH (−18.0±5.6 vs. −23.0±2.9; P<0.01) compared with controls. LV mass and interventricular septal thickness were lower in PAH patients (65.7±18.0 vs. 86.7±26.9 g and 7.6±1.9 vs. 10±2.4 mm; P<0.05); there were no differences in LV ejection fraction (61.2%±6.9% vs. 61.9%±6.7%; P=0.86). T1-derived parameters correlated significantly with RVS, LVS, the 6-minute walking distance, RV ejection fraction, pro-Brain Natriuretic Peptide, and baseline mean pulmonary arterial pressure. There were no significant differences in T2. Conclusions: In patients with PAH, changes in T1 and ECV support the hypothesis of LV myocardial fibrosis and atrophy with a consecutively impaired contractility despite a preserved LV function, possibly due to longstanding PAH-associated LV underfilling.