| 1. |
- Rauchmann, Boris Stephan, et al.
(författare)
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The impact of endurance training and table soccer on brain metabolites in schizophrenia
- 2020
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Ingår i: Brain Imaging and Behavior. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 14:2, s. 515-526
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Tidskriftsartikel (refereegranskat)abstract
- Higher glutamate and glutamine (together: Glx) and lower N-acetyl-aspartate (NAA) levels were reported in schizophrenia. Endurance training normalizes NAA in the hippocampus, but its effects on other metabolites in the brain and the relationship of metabolites to clinical symptoms remain unknown. For 12 weeks, 20 schizophrenia inpatients (14 men, 6 women) and 23 healthy controls (16 men, 7 women) performed endurance training and a control group of 21 schizophrenia inpatients (15 men, 6 women) played table soccer. A computer-assisted cognitive performance training program was introduced after 6 weeks. We assessed cognitive performance, psychopathological symptoms, and everyday functioning at baseline and after 6 and 12 weeks and performed single voxel magnetic resonance spectroscopy of the hippocampus, left dorsolateral prefrontal cortex (DLPFC), and thalamus. We quantified NAA, Glx, total creatine (tCr), calculated NAA/tCr and Glx/tCr and correlated these ratios with physical fitness, clinical and neurocognitive scores, and everyday functioning. At baseline, in both schizophrenia groups NAA/tCr was lower in the left DLPFC and left hippocampus and Glx/tCr was lower in the hippocampus than in the healthy controls. After 6 weeks, NAA/tCr increased in the left DLPFC in both schizophrenia groups. Brain metabolites did not change significantly in the hippocampus or thalamus, but the correlation between NAA/tCr and Glx/tCr normalized in the left DLPFC. Global Assessment of Functioning improvements correlated with NAA/tCr changes in the left DLPFC. In our study, endurance training and table soccer induced normalization of brain metabolite ratios in the brain circuitry associated with neuronal and synaptic elements, including metabolites of the glutamatergic system.
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| 2. |
- Baumeister, Hannah, et al.
(författare)
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A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings
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Ingår i: Brain : a journal of neurology. - 1460-2156. ; 147:7, s. 2400-2413
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Tidskriftsartikel (refereegranskat)abstract
- Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean ± SD age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (CU; n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (SCD; n = 342), mild cognitive impairment (MCI; n = 118), or dementia of the Alzheimer's type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid AD biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5), as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test if baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and MCI conversion rates of CU and SCD participants. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy first affected the medial temporal lobes, followed by further temporal and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological AD biomarker levels, APOE ε4 carriership, and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive AD biomarkers and was associated with more generalised cognitive impairment. Limbic-predominant atrophy, in all and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of MCI conversion. SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, both on the subject and group level, were excellent, indicating reliable performance in previously unseen data. The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for AD in applied settings. The implementation of atrophy subtype- and stage-specific end-points may increase the statistical power of pharmacological trials targeting early AD.
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| 4. |
- Dechent, Peter, et al.
(författare)
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Basal cerebral blood volume during the poststimulation undershoot in BOLD MRI of the human brain
- 2011
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016 .- 0271-678X. ; 31:1, s. 82-89
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Tidskriftsartikel (refereegranskat)abstract
- One of the characteristics of the blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) response to functional challenges of the brain is the poststimulation undershoot, which has been suggested to originate from a delayed recovery of either cerebral blood volume (CBV) or cerebral metabolic rate of oxygen to baseline. Using bolus-tracking MRI in humans, we recently showed that relative CBV rapidly normalizes after the end of stimulation. As this observation contradicts at least part of the blood-pool contrast agent studies performed in animals, we reinvestigated the CBV contribution by dynamic T1-weighted three-dimensional MRI (8 seconds temporal resolution) and Vasovist at 3 T (12 subjects). Initially, we determined the time constants of individual BOLD responses. After injection of Vasovist, CBV-related T1-weighted signal changes revealed a signal increase during visual stimulation (1.7%±0.4%), but no change relative to baseline in the poststimulation phase (0.2%±0.3%). This finding renders the specific nature of the contrast agent unlikely to be responsible for the discrepancy between human and animal studies. With the assumption of normalized cerebral blood flow after stimulus cessation, a normalized CBV lends support to the idea that the BOLD MRI undershoot reflects a prolonged elevation of oxidative metabolism.
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| 8. |
- Dreha-Kulaczewski, Steffi, et al.
(författare)
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Folate receptor α deficiency : Myelin‐sensitive MRI as a reliable biomarker to monitor the efficacy and long‐term outcome of a new therapeutic approach
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Ingår i: Journal of Inherited Metabolic Disease. - 0141-8955. ; , s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral folate transport deficiency, caused by a genetic defect in folate recep-torα, is a devastating neurometabolic disorder that, if untreated, leads to epi-leptic encephalopathy, psychomotor decline and hypomyelination. Currently,there are limited data on effective dosage and duration of treatment, thoughearly diagnosis and therapy with folinic acid appears critical. The aim of thislong-term study was to identify new therapeutic approaches and novel bio-markers for assessing efficacy, focusing on myelin-sensitive MRI. Clinical, bio-chemical, structural and quantitative MRI parameters of seven patients withgenetically confirmed folate receptorαdeficiency were acquired over 13 years.Multimodal MRI approaches comprised MR-spectroscopy (MRS), magnetiza-tion transfer (MTI) and diffusion tensor imaging (DTI) sequences. Patientsstarted oral treatment immediately following diagnosis or in an interval of upto 2.5 years. Escalation to intravenous and intrathecal administration was per-formed in the absence of effects. Five patients improved, one with a presymp-tomatic start of therapy remained symptom-free, and one with inconsistenttreatment deteriorated. While CSF 5-methyltetrahydrofolate and MRS parame-ters normalized immediately after therapy initiation, myelin-sensitive MTI andDTI measures correlated with gradual clinical improvement and ongoing mye-lination under therapy. Early initiation of treatment at sufficient doses, consid-ering early intrathecal applications, is critical for favorable outcome. Themajority of patients showed clinical improvements that correlated best withMTI parameters, allowing individualized monitoring of myelination recovery.Presymptomatic therapy seems to ensure normal development and warrantsnewborn screening. Furthermore, the quantitative parameters of myelin-sensitive MRI for therapy assessments can now be used for hypomyelinationdisorders in general.
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| 15. |
- Helms, Gunther, et al.
(författare)
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High-resolution maps of magnetization transfer with inherent correction for RF inhomogeneity and T1 relaxation obtained from 3D FLASH MRI
- 2008
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 60:6, s. 1396-1407
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Tidskriftsartikel (refereegranskat)abstract
- An empirical equation for the magnetization transfer (MT) FLASH signal is derived by analogy to dual-excitation FLASH, introducing a novel semiquantitative parameter for MT, the percentage saturation imposed by one MT pulse during TR. This parameter is obtained by a linear transformation of the inverse signal, using two reference experiments of proton density and T1 weighting. The influence of sequence parameters on the MT saturation was studied. An 8.5-min protocol for brain imaging at 3T was based on nonselective sagittal 3D-FLASH at 1.25mm isotropic resolution using partial acquisition techniques (TR/TE/flipangle = 25ms/4.9ms/5° or 11ms/4.9ms/15° for the T1 reference). A 12.8 ms Gaussian MT pulse was applied 2.2 kHz off-resonance with 540° flip angle. The MT saturation maps showed an excellent contrast in the brain due to clearly separated distributions for white and gray matter and cerebrospinal fluid. Within the limits of the approximation (excitation <15°, TR/T1<<1) the MT term depends mainly on TR, the energy and offset of the MT pulse, but hardly on excitation and T1 relaxation. It is inherently compensated for inhomogeneities of receive and transmit RF fields. The MT saturation appeared to be a sensitive parameter to depict MS lesions and alterations of normal-appearing white matter.
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| 16. |
- Helms, Gunther, et al.
(författare)
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Identification of signal bias in the variable flip angle method by linear display of the algebraic Ernst equation
- 2011
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 66:3, s. 669-677
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Tidskriftsartikel (refereegranskat)abstract
- A novel linear parameterization for the variable flip angle method for longitudinal relaxation time T1 quantification from spoiled steady state MRI is derived from the half angle tangent transform, t, of the flip angle. Plotting the signal S at coordinates x=St and y=S/t, respectively, establishes a line that renders signal amplitude and relaxation term separately as y-intercept and slope. This representation allows for estimation of the respective parameter from the experimental data. A comprehensive analysis of noise propagation is performed. Numerical results for efficient optimization of longitudinal relaxation time and proton density mapping experiments are derived. Appropriate scaling allows for a linear presentation of data that are acquired at different short pulse repetition times, TR << T1 thus increasing flexibility in the data acquisition by removing the limitation of a single pulse repetition time. Signal bias, like due to slice-selective excitation or imperfect spoiling, can be readily identified by systematic deviations from the linear plot. The method is illustrated and validated by 3T experiments on phantoms and human brain.
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| 18. |
- Helms, Gunther, et al.
(författare)
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Modeling the influence of TR and excitation flip angle on the magnetization transfer ratio (MTR) in human brain obtained from 3D spoiled gradient echo MRI
- 2010
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 64:1, s. 177-185
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Tidskriftsartikel (refereegranskat)abstract
- Attempts to optimize the magnetization transfer ratio (MTR) obtained from spoiled gradient echo MRI have focused on the properties of the magnetization transfer pulse. In particular, continuous-wave models do not explicitly account for the effects of excitation and relaxation on the MTR. In this work, these were modeled by an approximation of free relaxation between the radiofrequency pulses and of an instantaneous saturation event describing the magnetization transfer pulse. An algebraic approximation of the signal equation can be obtained for short pulse repetition time and small flip angles. This greatly facilitated the mathematical treatment and understanding of the MTR. The influence of inhomogeneous radiofrequency fields could be readily incorporated. The model was verified on the human brain in vivo at 3 T by variation of flip angle and pulse repetition time. The corresponding range in MTR was similar to that observed by a 4-fold increase of magnetization transfer pulse power. Choice of short pulse repetition time and larger flip angles improved the MTR contrast and reduced the influence of radiofrequency inhomogeneity. Optimal contrast is obtained around an MTR of 50%, and noise progression is reduced when a high reference signal is obtained.
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| 19. |
- Helms, Gunther, et al.
(författare)
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Pharmacokinetics of the MRI contrast agent gadobutrol in common marmoset monkeys (Callithrix jacchus)
- 2016
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Ingår i: Journal of Medical Primatology. - : Wiley. - 0047-2565. ; 45:6, s. 290-296
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study determined the pharmacokinetics of the contrast agent gadobutrol in marmosets by quantitative MRI to derive guidelines for neuroimaging protocols. Methods: Local concentrations of gadobutrol were determined from consecutive gradient echo-based mapping of the relaxation rate R1 on a clinical 3T MRI scanner. Half-time of renal elimination was measured after injection of a triple dose of gadobutrol (0.3 mmol/kg) into the saphenous vein. A first-order single-compartment model was fitted to the measured R1 values and verified by blood analysis. Results: Slow injection (1.5 minutes) resulted in an elimination half-time of 26±4 minutes. After bolus injection (15 seconds), elimination was much slower (62±8 minutes) with 45% larger distribution volumes. Importantly, more gadobutrol entered the cerebrospinal fluid. Conclusions: Slow injection and a latency of about 20 minutes are recommended to avoid extravasation. Application of a triple dose of gadobutrol compensates for the fast elimination in healthy marmosets.
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| 20. |
- Helms, Gunther, et al.
(författare)
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Quantitative FLASH MRI at 3T using a rational approximation of the Ernst equation
- 2008
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 59:4, s. 667-672
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Tidskriftsartikel (refereegranskat)abstract
- From the half-angle substitution of trigonometric terms in the Ernst equation, rational approximations of the flip angle dependence of the FLASH signal can be derived. Even the rational function of the lowest order was in good agreement with the experiment for flip angles up to 20°. Three-dimensional maps of the signal amplitude and longitudinal relaxation rates in human brain were obtained from eight subjects by dual-angle measurements at 3T (nonselective 3D-FLASH, 7° and 20° flip angle, TR=30ms, isotropic resolution of 0.95mm, each 7:09 min). The corresponding estimates of T1 and signal amplitude are simple algebraic expressions and deviated about 1% from the exact solution. They are ill-conditioned to estimate the local flip angle deviation but can be corrected post hoc by division of squared RF maps obtained by independent measurements. Local deviations from the nominal flip angles strongly affected the relaxation estimates and caused considerable blurring of the T1 histograms.
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| 21. |
- Helms, Gunther, et al.
(författare)
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Rapid radiofrequency field mapping in vivo using single-shot STEAM MRI
- 2008
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 60:3, s. 739-743
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Tidskriftsartikel (refereegranskat)abstract
- Higher field strengths entail less homogeneous RF fields. This may influence quantitative MRI and MRS. A method for rapidly mapping the RF field in the human head with minimal distortion was developed on the basis of a single-shot stimulated echo acquisition mode (STEAM) sequence. The flip angle of the second RF pulse in the STEAM preparation was set to 60° and 100° instead of 90°, inducing a flip angle-dependent signal change. A quadratic approximation of this trigonometric signal dependence together with a calibration accounting for slice excitation-related bias allowed for directly determining the RF field from the two measurements only. RF maps down to the level of the medulla could be obtained in less than 1 min and registered to anatomical volumes by means of the T2-weighted STEAM images. Flip angles between 75% and 125% of the nominal value were measured in line with other methods.
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| 22. |
- Helms, Gunther, et al.
(författare)
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Resampling Strategies to Estimate Mean Concentrations from Low SNR In Vivo MR Spectra
- 2007
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Ingår i: Proc. Intl. Soc. Mag. Reson. Med.. - 1524-6965 .- 1524-6965. ; 15
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Konferensbidrag (refereegranskat)abstract
- A resampling method for quantitative MRS is presented that retains absolute concentrations. Averaging the spectra from a subset improved the concentrationestimates via increased SNR. Using short-TE STEAM spectra from human thalamus, the influence of subset size was systematically studied and verifiedagainst conventional bootstrap re-sampling. Even small subsets provided considerably better signal-to-noise ratio and reliability. The standard deviation orconfidence intervals can be derived by correcting the variance over all subset estimates for the inherent redundancy. Subsets of about half the group size arerecommended, because of their large number and the almost normal distribution of mean concentration estimates.
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| 25. |
- Liopyris, Konstantinos, et al.
(författare)
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Expert agreement on the presence and spatial localization of melanocytic features in dermoscopy.
- 2023
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Ingår i: The Journal of investigative dermatology. - 1523-1747. ; 144:3
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Tidskriftsartikel (refereegranskat)abstract
- Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. Herein we attempted to evaluate agreement among experts on 'exemplar images' not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least one of 31 melanocytic-specific features were submitted by 25 world experts as 'exemplars'. Using a web-based platform that allows for image mark-up of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with 8 achieving excellent agreement (Gwet's AC >0.75) and 7 of them being melanoma-specific features. These features were: 'Peppering /Granularity' (0.91); 'Shiny White Streaks' (0.89); 'Typical Pigment network' (0.83); 'Blotch Irregular' (0.82); 'Negative Network' (0.81); 'Irregular Globules' (0.78); 'Dotted Vessels' (0.77) and 'Blue Whitish Veil' (0.76). By utilizing an exemplar dataset, good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication and machine learning experiments.
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