Tanja Haas

Dynamic reconfiguration of human brain functional networks through neurofeedback

Recent fMRI studies demonstrated that functional connectivity is altered following cognitive tasks (e.g., learning) or due to various neurological disorders. We tested whether real-time fMRI-based neurofeedback can be a tool to voluntarily reconfigure brain network interactions. To disentangle learning-related from regulation-related effects, we first trained participants to voluntarily regulate activity in the auditory cortex (training phase) and subsequently asked participants to exert learned voluntary self-regulation in the absence of feedback (transfer phase without learning). Using independent component analysis (ICA), we found network reconfigurations (increases in functional network connectivity) during the neurofeedback training phase between the auditory target region and (1) the auditory pathway; (2) visual regions related to visual feedback processing; (3) insula related to introspection and self-regulation and (4) working memory and high-level visual attention areas related to cognitive effort. Interestingly, the auditory target region was identified as the hub of the reconfigured functional networks without a-priori assumptions. During the transfer phase, we again found specific functional connectivity reconfiguration between auditory and attention network confirming the specific effect of self-regulation on functional connectivity. Functional connectivity to working memory related networks was no longer altered consistent with the absent demand on working memory. We demonstrate that neurofeedback learning is mediated by widespread changes in functional connectivity. In contrast, applying learned self-regulation involves more limited and specific network changes in an auditory setup intended as a model for tinnitus. Hence, neurofeedback training might be used to promote recovery from neurological disorders that are linked to abnormal patterns of brain connectivity.

Quantification of fat infiltration in oculopharyngeal muscular dystrophy: Comparison of three MR imaging methods

To analyze and compare three quantitative MRI methods to determine the degree of muscle involvement in oculopharyngeal muscular dystrophy (OPMD).

Quantitative muscle MRI: A powerful surrogate outcome measure in Duchenne muscular dystrophy

In muscular dystrophies quantitative muscle MRI (qMRI) detects disease progression more sensitively than clinical scores. This prospective one year observational study compared qMRI with clinical scores in Duchenne muscular dystrophy (DMD) to investigate if qMRI can serve as a surrogate outcome measure in clinical trials. In 20 DMD patients the motor function measure (MFM) total and subscores (D1-D3) were done for physical examination, and the fat fraction (MFF) of thigh muscle qMRI was obtained using the two-point Dixon method. Effect sizes (ES) were calculated for all measures. Sample size estimation (SS) was done modelling assumed treatment effects. Ambulant patients <7 years at inclusion improved in the MFM total and D1 score (ES 1.1 and 1.0). Ambulant patients >7 years (highest ES in the MFM D1 subscore (1.2)), and non-ambulant patients (highest ES in the total MFM score (0.7)) worsened. In comparison the ES of QMRI was much larger, e.g. SS estimations for qMRI data were up to 17 fold smaller compared to the MFM total score and up to 7 fold to the D1 subscore, respectively. QMRI shows pathophysiological changes in DMD and might serve as a surrogate outcome measure in clinical trials.

Altered cerebrovascular reactivity velocity in mild cognitive impairment and Alzheimer's disease

Interindividual variation in neurovascular reserve and its relationship with cognitive performance is not well understood in imaging in neurodegeneration. We assessed the neurovascular reserve in amnestic mild cognitive impairment (aMCI) and Alzheimers dementia (AD). Twenty-eight healthy controls (HC), 15 aMCI, and 20 AD patients underwent blood oxygen level-dependent imaging for 9 minutes, breathing alternatively air and 7% carbon dioxide mixture. The data were parcellated into 88 anatomic regions, and carbon dioxide regressors accounting for different washin and washout velocities were fitted to regional average blood oxygen level-dependent signals. Velocity of cerebrovascular reactivity (CVR) was analyzed and correlated with cognitive scores. aMCI and AD patients had significantly slower response than HC (mean time to reach 90% of peak: HC 33 seconds, aMCI and AD 59 seconds). CVR velocity correlated with Mini Mental State Examination in 35 of 88 brain regions (p = 0.019, corrected for multiple comparisons), including 10 regions of the default-mode network, an effect modulated by age. This easily applicable protocol yielded a practical assessment of CVR in cognitive decline.

Recovery of the default mode network after demanding neurofeedback training occurs in spatio-temporally segregated subnetworks

The default mode (DM) network is a major large-scale cerebral network that can be identified with functional magnetic resonance imaging (fMRI) during resting state. Most studies consider functional connectivity networks as stationary phenomena. Consequently, the transient behavior of the DM network and its subnetworks is still largely unexplored. Most functional connectivity fMRI studies assess the steady state of resting without any task. To specifically investigate the recovery of the DM network during the transition from activation to rest, we implemented a cognitively demanding real-time fMRI neurofeedback task that targeted down-regulation of the primary auditory cortex. Each of twelve healthy subjects performed 16 block-design fMRI runs (4 runs per day repeated on 4 days) resulting 192 runs in total. The analysis included data-driven independent component analysis (ICA) and high-resolution latency estimation between the four components that corresponded to subnetworks of the DM network. These different subnetworks reemerged after regulation with an average time lag or 3.3s and a time lag of 4.4s between the first and fourth components; i.e., the DM recovery first shifts from anterior to posterior, and then gradually focuses on the ventral part of the posterior cingulate cortex, which is known to be implicated in internally directed cognition. In addition, we found less reactivation in the early anterior subnetwork as regulation strength increased, but more reactivation with larger regulation for the late subnetwork that encompassed the ventral PCC. This finding confirms that the level of task engagement influences inversely the subsequent recovery of regions related to attention compared to those related to internally directed cognition.

Longitudinal 2-point dixon muscle magnetic resonance imaging in becker muscular dystrophy.

Introduction: Quantitative MRI techniques detect disease progression in myopathies more sensitively than muscle function measures or conventional MRI. To date, only conventional MRI data using visual rating scales are available for measurement of disease progression in Becker muscular dystrophy (BMD). Methods: In 3 patients with BMD (mean age 36.8 years), the mean fat fraction (MFF) of the thigh muscles was assessed by MRI at baseline and at 1‐year follow‐up using a 2‐point Dixon approach (2PD). The motor function measurement scale (MFM) was used for clinical assessment. Results: The mean MFF of all muscles at baseline was 61.6% (SD 7.6). It increased by 3.7% to 65.3% (SD 4.7) at follow‐up. The severity of muscle involvement varied between various muscle groups. Conclusions: As in other myopathies, 2PD can quantify fatty muscle degeneration in BMD and can detect disease progression in a small sample size and at relatively short imaging intervals. Muscle Nerve 51: 918–921, 2015

MR-imaging of the thoracic aorta: 3D-ECG- and respiratory-gated bSSFP imaging using the CLAWS algorithm versus contrast-enhanced 3D-MRA

OBJECTIVE To compare a contrast-enhanced 3D angiography (CE-3D-MRA) with the ECG- and respiratory gated 3D balanced steady state free precession (bSSFP) sequence using the CLAWS algorithm (3D-bSSFP-CLAWS) with respect to acquisition time, image quality, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). METHODS 14 patients (4 women, mean age ± SD: 52 ± 18) with known or suspected thoracic aortic disease were imaged on a 1.5T scanner with both sequences. Two readers scored image quality of predefined levels of the thoracic aorta. Acquisition time, SNR and CNR were calculated for each examination. RESULTS Image quality achieved with the 3D-bSSFP-CLAWS was scored significantly better than with the CE-3D-MRA for the aortic annulus (P = 0.003), the sinuses of Valsalva (P = 0.001), the proximal coronary arteries (P = 0.001) and the sinotubular junction (P = 0.001). Effective acquisition time for the 3D-bSSFP-CLAWS and corrected acquisition time (corrected for imaging parameters) was significantly longer compared to the CE-3D-MRA (P = 0.004 and P = 0.028). SNR and CNR were significantly higher for the CE-3D-MRA (P = 0.007 and P = 0.001). CONCLUSIONS Providing the highest scan efficiency for a given breathing pattern, image quality for the proximal ascending aorta achieved with the 3D-bSSFP-CLAWS is significantly superior in contrast to the CE-3D-MRA.

Effect of protein binding substances on T1 times and the partition coefficient in contrast-enhanced cardiac magnetic resonance imaging

Background Diffuse myocardial fibrosis is present in several cardiomyopathies. Contrast enhanced cardiac MR with T1 mapping enables quantification of diffuse fibrosis. T1 mapping is technically demanding since technical, physiological, and biochemical factors can interfere with T1 measurements. Contrast material dose, relaxivity, biodistribution, clearance, interaction with plasma proteins, and interference with co-medication must be taken into consideration. Gadobenate dimeglumine (GdBOPTA) has some weak protein binding capacities and higher molar relaxivity in plasma/blood resulting in shorter T1 times as compared to other extracellular gadolinium based contrast agents. To date it has not been assessed whether co-medication with other protein binding drugs alter myocardial T1 time. Therefore the aim of this study was to evaluate the interference of a typical protein binding drug (Ibuprofen) with GdBOPTA with respect to T1 times in vitro and in vivo. Methods

The protein binding substance ibuprofen does not affect the T1 time or partition coefficient in contrast-enhanced cardiovascular magnetic resonance.

BackgroundContrast enhanced cardiovascular magnetic resonance (CMR) with T1 mapping enables quantification of diffuse myocardial fibrosis. Various factors, however, can interfere with T1 measurements. The purpose of the current study was to assess the effect of co-medication with a typical protein binding drug (Ibuprofen) on T1 values in vitro and in vivo.Methods50 vials were prepared with different concentrations of gadobenate dimeglumine, Ibuprofen and human serum albumin in physiologic NaCl solution and imaged at 1.5T with a spin echo sequence at multiple TRs to measure T1 values and calculate relaxivities. 10 volunteers (5 men; 31±6.3 years) were imaged at 1.5T. T1 values for myocardium and blood pool were determined for various time points after administration of 0.15mmol/kg gadobenate dimeglumine using a modified look-locker inversion-recovery sequence before and after administration of Ibuprofen over 24 hours. The partition coefficient was calculated as ΔR1myocardium/ΔR1blood, where R1=1/T1.ResultsIn vitro no significant correlation was found between relaxivity and Ibuprofen concentration, neither in absence (r=−0.15, p=0.40) nor in presence of albumin (r=−0.32, p=0.30). In vivo there was no significant difference in post contrast T1 times of myocardium and blood, respectively and also in the partition coefficient between exam 1 and 2 (p>0.05). There was good agreement of the T1 times of myocardium and blood and the partition coefficient, respectively between exam 1 and 2.ConclusionsContrast enhanced T1 mapping is unaffected by co-medication with the protein binding substance Ibuprofen and has an excellent reproducibility.

Normal response of cardiac flow and function to adenosine stress as assessed by cardiac MR.

Aims To establish the response of cardiac flow and function to adenosine stress using phase-contrast magnetic resonance (pcMR) and cine steady-state free precession (SSFP) cardiac magnetic resonance (CMR). Methods Healthy volunteers (n = 10) were scanned on 1.5T at rest and under adenosine stress utilizing short-axis SSFP sequences and pcMR of the aorta and pulmonary trunk. Results Adenosine-induced increase in heart rate was 62.7% (P < 0.001). Left and right-ventricular stroke volumes (SVs) increased by 12.2% (P = 0.048) and 11.9% (P = 0.044), left-ventricular ejection fraction by 11.8% (P = 0.002), and left-ventricular and right-ventricular cardiac output (CO) by 81.0% (P < 0.001) and 81.8% (P = 0.005). Average flow velocities in the ascending aorta and pulmonary trunk increased by 77.3% (P < 0.001) and 73.6% (P < 0.001), and peak flow velocities in the ascending aorta and pulmonary trunk by 27.2% (P < 0.001) and 22.4% (P = 0.003). End-systolic volumes in the left ventricle (LV) and right ventricle (RV) decreased by 16.4% (P = 0.020) and 19.2% (P = 0.028). Planimetric cine SSFP and pcMR-derived SV showed an excellent correlation. Conclusion In healthy volunteers, response to adenosine stress is characterized by an increase in heart rate, CO and SV of both ventricles. Excellent correlation is demonstrated between these increases and the increased blood flow velocities in the aorta and the pulmonary trunk. Thus, results support the use of flow measurements as an internal control of planimetric measurements of ventricular SV and CO.