Diffusion tensor imaging in pediatric patients with dystonia.

BACKGROUND: Childhood-onset dystonia is often progressive and severely impairs a child´s life. The pathophysiology is very heterogeneous and treatment responses vary in patients with dystonia. Factors influencing treatment effects remain to be elucidated. We hypothesize that differences in brain connectivity and fiber coherence contribute to the heterogeneity in treatment response among pediatric patients with inherited and acquired dystonia. METHODS: Twenty patients with childhood-onset dystonia were retrospectively recruited including twelve patients with inherited or idiopathic, and eight patients with acquired dystonia (mean age 10 years; 8 female/12 male). Fiber density between the internal part of the globus pallidus and selective target regions, as well as the diffusion measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed and compared between different etiologies. RESULTS: Patients with acquired dystonia presented higher fiber density to the premotor cortex and putamen and lower FA values in the thalamus compared to patients with inherited/idiopathic dystonia. MD in the premotor cortex was higher in patients with acquired dystonia, while it was lower in the thalamus. CONCLUSION: Diffusion MRI reveals microstructural and network alterations in patients with dystonia of different etiologies.

Influence of Ultrasound Settings on Laboratory Vertical Artifacts.

OBJECTIVE: The aim of the work described here was to analyze the relationship between the change in ultrasound (US) settings and the vertical artifacts' number, visual rating and signal intensity METHODS: An in vitro phantom consisting of a damp sponge and gelatin mix was created to simulate vertical artifacts. Furthermore, several US parameters were changed sequentially (i.e., frequency, dynamic range, line density, gain, power and image enhancement) and after image acquisition. Five US experts rated the artifacts for number and quality. In addition, a vertical artifact visual score was created to determine the higher artifact rating ("optimal") and the lower artifact rating ("suboptimal"). Comparisons were made between the tested US parameters and baseline recordings. RESULTS: The expert intraclass correlation coefficient for the number of vertical artifacts was 0.694. The parameters had little effect on the "optimal" vertical artifacts but changed their number. Dynamic range increased the number of discernible vertical artifacts to 3 from 36 to 102 dB. CONCLUSION: The intensity did not correlate with the visual rating score. Most of the available US parameters did not influence vertical artifacts.

Digital participation of brain tumour patients in the assessment and treatment of communication disorders.

Introduction: Communication deficits have a severe impact on our social interactions and health-related quality of life. Subtle communication deficits are frequently overlooked or neglected in brain tumour patients, due to insufficient diagnostics. Digital tools may represent a valuable adjunct to the conventional assessment or therapy setting but might not be readily suitable for every patient. Methods: This article summarises results of three surveys on the readiness for telemedicine among (a) patients diagnosed with high-grade glioma, (b) matched controls, and (c) speech and language therapists. The respective surveys assessed the motivation for participation in telemedical assessments and supposed influencing factors, and the use potential of digital assessment and therapy technologies in daily routine, with a spotlight on brain tumour patients and the future prospects of respective telemedical interventions. Respondents included 56 high-grade glioma patients (age median: 59 years; 48% males), 73 propensity-score matched neurologically healthy controls who were instructed to imagine themselves with a severe disease, and 23 speech and language therapists (61% <35 years; all females). Results and discussion: The vast majority of the interviewed high-grade glioma (HGG) patients was open to digitisation, felt well-equipped and sufficiently skilled. The factorial analysis showed that digital offers would be of particular interest for patients in reduced general health condition (p = 0.03) and those who live far from specialised treatment services (p = 0.03). The particular motivation of these subgroups seemed to outweigh the effects of age, equipment and internet skills, which were only significant in the control cohort. The therapists' survey demonstrated a broad consensus on the need for improving the therapy access of brain tumour patients (64%) and strengthening their respective digital participation (78%), although digitisation seems to have yet hardly entered the therapists' daily practise. In summary, the combined results of the surveys call for a joint effort to enhance the prerequisites for digital participation of patients with neurogenic communication disorders, particularly in the context of heavily burdened HGG patients with limited mobility.

Connectivity in deep brain stimulation for self-injurious behavior: multiple targets for a common network?

Self-injurious behavior (SIB) is associated with diverse psychiatric conditions. Sometimes (e.g., in patients with autism spectrum disorder or acquired brain injuries), SIB is the most dominant symptom, severely restricting the psychosocial functioning and quality of life of the patients and inhibiting appropriate patient care. In severe cases, it can lead to permanent physical injuries or even death. Primary therapy consists of medical treatment and if implementable, behavioral therapy. For patients with severe SIB refractory to conventional therapy, neuromodulation can be considered as a last recourse. In scientific literature, several successful lesioning and deep brain stimulation targets have been described that can indicate a common underlying neuronal pathway. The objectives of this study were to evaluate the short- and long-term clinical outcome of patients with severe, therapy refractory SIB who underwent DBS with diverse underlying psychiatric disorders and to correlate these outcomes with the activated connectivity networks. We retrospectively analyzed 10 patients with SIB who underwent DBS surgery with diverse psychiatric conditions including autism spectrum disorder, organic personality disorder after hypoxic or traumatic brain injury or Tourette syndrome. DBS targets were chosen according to the underlying disorder, patients were either stimulated in the nucleus accumbens, amygdala, posterior hypothalamus, medial thalamus or ventrolateral thalamus. Clinical outcome was measured 6 months after surgery and at long-term follow-up after 10 or more years using the Early Rehabilitation Barthel index (ERBI) and time of restraint. Connectivity patterns were analyzed using normative connectome. Based on previous literature the orbitofrontal cortex, superior frontal gyrus, the anterior cingulate cortex, the amygdala and the hippocampus were chosen as regions of interest. This analysis showed a significant improvement in the functionality of the patients with DBS in the short- and long-term follow-up. Good clinical outcome correlated with higher connectivity to the amygdala and hippocampus. These findings may suggest a common pathway, which can be relevant when planning a surgical procedure in patients with SIB.

Surgery of Motor Eloquent Glioblastoma Guided by TMS-Informed Tractography: Driving Resection Completeness Towards Prolonged Survival.

Background: Surgical treatment of patients with glioblastoma affecting motor eloquent brain regions remains critically discussed given the risk-benefit dilemma of prolonging survival at the cost of motor-functional damage. Tractography informed by navigated transcranial magnetic stimulation (nTMS-informed tractography, TIT) provides a rather robust estimate of the individual location of the corticospinal tract (CST), a highly vulnerable structure with poor functional reorganisation potential. We hypothesised that by a more comprehensive, individualised surgical decision-making using TIT, tumours in close relationship to the CST can be resected with at least equal probability of gross total resection (GTR) than less eloquently located tumours without causing significantly more gross motor function harm. Moreover, we explored whether the completeness of TIT-aided resection translates to longer survival. Methods: A total of 61 patients (median age 63 years, m = 34) with primary glioblastoma neighbouring or involving the CST were operated on between 2010 and 2015. TIT was performed to inform surgical planning in 35 of the patients (group T; vs. 26 control patients). To achieve largely unconfounded group comparisons for each co-primary outcome (i.e., gross-motor functional worsening, GTR, survival), (i) uni- and multivariate regression analyses were performed to identify features of optimal outcome prediction; (ii), optimal propensity score matching (PSM) was applied to balance those features pairwise across groups, followed by (iii) pairwise group comparison. Results: Patients in group T featured a significantly higher lesion-CST overlap compared to controls (8.7 ± 10.7% vs. 3.8 ± 5.7%; p = 0.022). The frequency of gross motor worsening was higher in group T, albeit non-significant (n = 5/35 vs. n = 0/26; p = 0.108). PSM-based paired-sample comparison, controlling for the confounders of preoperative tumour volume and vicinity to the delicate vasculature of the insula, showed higher GTR rates in group T (77% vs. 69%; p = 0.025), particularly in patients with a priori intended GTR (87% vs. 78%; p = 0.003). This translates into a prolonged PFS in the same PSM subgroup (8.9 vs. 5.8 months; p = 0.03), with GTR representing the strongest predictor of PFS (p = 0.001) and OS (p = 0.0003) overall. Conclusion: The benefit of TIT-aided GTR appears to overcome the drawbacks of potentially elevated motor functional risk in motor eloquent tumour localisation, leading to prolonged survival of patients with primary glioblastoma close to the CST.

A Fast Protocol for Multiparametric Characterisation of Diffusion in the Brain and Brain Tumours.

Multi-parametric tissue characterisation is demonstrated using a 4-minute protocol based on diffusion trace acquisitions. Three diffusion regimes are covered simultaneously: pseudo-perfusion, Gaussian, and non-Gaussian diffusion. The clinical utility of this method for fast multi-parametric mapping for brain tumours is explored. A cohort of 17 brain tumour patients was measured on a 3T hybrid MR-PET scanner with a standard clinical MRI protocol, to which the proposed multi-parametric diffusion protocol was subsequently added. For comparison purposes, standard perfusion and a full diffusion kurtosis protocol were acquired. Simultaneous amino-acid (18F-FET) PET enabled the identification of active tumour tissue. The metrics derived from the proposed protocol included perfusion fraction, pseudo-diffusivity, apparent diffusivity, and apparent kurtosis. These metrics were compared to the corresponding metrics from the dedicated acquisitions: cerebral blood volume and flow, mean diffusivity and mean kurtosis. Simulations were carried out to assess the influence of fitting methods and noise levels on the estimation of the parameters. The diffusion and kurtosis metrics obtained from the proposed protocol show strong to very strong correlations with those derived from the conventional protocol. However, a bias towards lower values was observed. The pseudo-perfusion parameters showed very weak to weak correlations compared to their perfusion counterparts. In conclusion, we introduce a clinically applicable protocol for measuring multiple parameters and demonstrate its relevance to pathological tissue characterisation.

Impact of Navigated Task-specific fMRI on Direct Cortical Stimulation.

BACKGROUND AND STUDY AIMS: Cortical mapping (CM) with direct cortical stimulation (DCS) in awake craniotomy is used to preserve cognitive functions such as language. Nevertheless, patient collaboration during this procedure is influenced by previous neurological symptoms and growing discomfort with DCS duration. Our study aimed to evaluate the impact of navigated task-specific functional magnetic resonance imaging (nfMRI) on the practical aspects of DCS. MATERIAL AND METHODS: We recruited glioma patients scheduled for awake craniotomy for prior fMRI-based CM, acquired during motor and language tasks (i.e., verb generation, semantic and syntactic decision tasks). Language data was combined to generate a probabilistic map indicating brain regions activated with more than one paradigm. Presurgical neurophysiological language tests (i.e., verb generation, picture naming, and semantic tasks) were also performed. We considered for subsequent study only the patients with a minimum rate of correct responses of 50% in all tests. These patients were then randomized to perform intraoperative language CM either using the multimodal approach (mCM), using nfMRI and DCS combined, or electrical CM (eCM), with DCS alone. DCS was done while the patient performed picture naming and nonverbal semantic decision tasks. Methodological features such as DCS duration, number of stimuli, total delivered stimulus duration per task, and frequency of seizures were analyzed and compared between groups. The correspondence between positive responses obtained with DCS and nfMRI was also evaluated. RESULTS: Twenty-one surgeries were included, thirteen of which using mCM (i.e., test group). Patients with lower presurgical neuropsychological performance (correct response rate between 50 and 80% in language tests) showed a decreased DCS duration in comparison with the control group. None of the compared methodological features showed differences between groups. Correspondence between DCS and nfMRI was 100/84% in the identification of the precentral gyrus for motor function/opercular frontal inferior gyrus for language function, respectively. CONCLUSION: Navigated fMRI data did not influence DCS in practice. Presurgical language disturbances limited the applicability of DCS mapping in awake surgery.

Quantitative MRI of cerebral white matter hyperintensities: A new approach towards understanding the underlying pathology.

Interest in white matter hyperintensities (WMH), a radiological biomarker of small vessel disease, is continuously increasing. This is, in most part, due to our better understanding of their association with various clinical disorders, such as stroke and Alzheimer's disease, and the overlapping pathology of WMH with these afflictions. Although post-mortem histological studies have reported various underlying pathophysiological substrates, in vivo research has not been specific enough to fully corroborate these findings. Furthermore, post-mortem studies are not able to capture which pathological processes are the driving force of the WMH severity. The current study attempts to fill this gap by non-invasively investigating the influence of WMH on brain tissue using quantitative MRI (qMRI) measurements of the water content (H2O), the longitudinal (T1) and effective transverse relaxation times (T2∗), as well as the semi-quantitative magnetization transfer ratio (MTR), and bound proton fraction (ƒbound). In total, seventy subjects (age range 50-80 years) were selected from a population-based aging cohort study, 1000BRAINS. Normal appearing grey (NAGM) and white matter (NAWM), as well as deep (DWMH) and periventricular (PWMH) white matter hyperintensities, were segmented and characterized in terms of their quantitative properties. The subjects were then further divided into four grades according to the Fazekas rating scale of severity. Groupwise analyses of the qMRI values in each tissue class were performed. All five qMRI parameters showed significant differences between WMH and NAWM (p < 0.001). Importantly, the parameters differed between DWMH and PWMH, the latter having higher H2O, T1, T2∗ and lower MTR and ƒbound values (p < 0.001). Following grading according to the Fazekas scale, DWMH showed an increase in the water content, T1 and a decrease in bound proton fraction corresponding to severity, exhibiting significant changes in grade 3 (p < 0.001), while NAWM revealed significantly higher H2O values in grade 3 compared to grade 0 (p < 0.001). PWMH demonstrated an increase in T2∗ values (significant in grade 3, P < 0.001). These results are in agreement with previous histopathological studies and support the interpretation that both edema and myelin loss due to a possible breakdown of the blood-brain barrier and inflammation are the major pathological substrates turning white matter into DWMH. Edema being an earlier contributing factor to the pathology, as expressed in the elevated water content values in NAWM with increasing severity. In the case of PWMH, an altered fluid dynamic and cerebrospinal fluid leakage exacerbate the changes. It was also found that the pathology, as monitored by qMRI, evolves faster in DWMH than in the PWMH following the severity.

Gamma Distribution Model in the Evaluation of Breast Cancer Through Diffusion-Weighted MRI: A Preliminary Study.

BACKGROUND: The gamma distribution (GD) model is based on the statistical distribution of the apparent diffusion coefficient (ADC) parameter. The GD model is expected to reflect the probability of the distribution of water molecule mobility in different regions of tissue, but also the intra- and extracellular diffusion and perfusion components (f1 , f2 , f3 fractions). PURPOSE: To assess the GD model in the characterization and diagnostic performance of breast lesions. STUDY TYPE: Prospective. POPULATION: In all, 48 females with 24 benign and 33 malignant breast lesions. FIELD STRENGTH/SEQUENCE: A diffusion-weighted sequence (b = 0-3000 s/mm2 ) with a 3 T scanner. ASSESSMENT: For each group of benign, malignant, invasive, and in situ breast lesions, the ADC was obtained. Also, θ and k parameters (scale and shape of the statistic distribution, respectively), f1 , f2 , and f3 fractions were obtained from fitting the GD model to diffusion data. STATISTICAL TESTS: Lesion types were compared regarding diffusion parameters using nonparametric statistics and receiver operating characteristic curve diagnostic performance. RESULTS: The majority of GD parameters (k, f1 , f2 , f3 fractions) showed significant differences between benign and malignant lesions, and between in situ and invasive lesions (f1 , f2 , f3 fractions) (P ≤ 0.001). The best diagnostic performances were obtained with ADC and f1 fraction in benign vs. malignant lesions (area under curve [AUC] = 0.923 and 0.913, sensitivity = 93.9% and 81.8%, specificity = 79.2% and 91.7%, accuracy = 87.7% and 86.0%, respectively). In invasive lesions vs. in situ lesions, the best diagnostic performance was obtained with f1 fraction, which outperformed ADC results (AUC = 0.978 and 0.941, and sensitivity = 91.3% for both parameters, specificity = 100.0% and 90.0%, accuracy = 93.9% and 90.9%, respectively). DATA CONCLUSION: This work shows that the GD model provides information in addition to the ADC parameter, suggesting its potential in the diagnosis of breast lesions. Level of Evidence 2: Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2019;50:230-238.

A Single-Scan, Rapid Whole-Brain Protocol for Quantitative Water Content Mapping With Neurobiological Implications.

Water concentration is tightly regulated in the healthy human brain and changes only slightly with age and gender in healthy subjects. Consequently, changes in water content are important for the characterization of disease. MRI can be used to measure changes in brain water content, but as these changes are usually in the low percentage range, highly accurate and precise methods are required for detection. The method proposed here is based on a long-TR (10 s) multiple-echo gradient-echo measurement with an acquisition time of 7:21 min. Using such a long TR ensures that there is no T1 weighting, meaning that the image intensity at zero echo time is only proportional to the water content, the transmit field, and to the receive field. The receive and transmit corrections, which are increasingly large at higher field strengths and for highly segmented coil arrays, are multiplicative and can be approached heuristically using a bias field correction. The method was tested on 21 healthy volunteers at 3T field strength. Calibration using cerebral-spinal fluid values (~100% water content) resulted in mean values and standard deviations of the water content distribution in white matter and gray matter of 69.1% (1.7%) and 83.7% (1.2%), respectively. Measured distributions were coil-independent, as seen by using either a 12-channel receiver coil or a 32-channel receiver coil. In a test-retest investigation using 12 scans on one volunteer, the variation in the mean value of water content for different tissue types was ~0.3% and the mean voxel variability was ~1%. Robustness against reduced SNR was assessed by comparing results for 5 additional volunteers at 1.5T and 3T. Furthermore, water content distribution in gray matter is investigated and regional contrast reported for the first time. Clinical applicability is illustrated with data from one stroke patient and one brain tumor patient. It is anticipated that this fast, stable, easy-to-use, high-quality mapping method will facilitate routine quantitative MR imaging of water content.

Reconstruction of white matter fibre tracts using diffusion kurtosis tensor imaging at 1.5T: Pre-surgical planning in patients with gliomas.

Tractography studies for pre-surgical planning of primary brain tumors is typically done using diffusion tensor imaging (DTI), which cannot resolve crossing, kissing or highly angulated fibres. Tractography based on the estimation of the diffusion kurtosis (DK) tensor was recently demonstrated to enable tackling these limitations. However, its use in the clinical context at low 1.5T field has not yet been reported. PURPOSE: To evaluate if the estimation of whole-brain tractography using the DK tensor is feasible for pre-surgical investigation of patients with brain tumors at 1.5T. METHODS: Eight healthy subjects and 3 patients with brain tumors were scanned at 1.5T using a 12-channel head coil. Diffusion-weighted images were acquired with repetition/echo times of 5800/107 ms, 82 × 82 resolution, 3 × 3 × 3 mm3 voxel size, b-values of 0, 1000, 2000 s/mm2 and 64 gradient sensitising directions. Whole-brain tractography was estimated using the DK tensor and corticospinal tracts (CST) were isolated using regions-of-interest placed at the cerebral peduncles and motor gyrus. Tract size, DK metrics and CST deviation index (highest curvature point) were compared between healthy subjects and patients. RESULTS: Tract sizes did not differ between groups. The CST deviation index was significantly higher in patients compared to healthy subjects. Fractional anisotropy was significantly lower in patients, with higher mean kurtosis asymmetry index at the highest curvature point in patients. CONCLUSIONS: Corticospinal fibre bundles estimated using DK tensor in a 1.5T scanner presented similar properties in patients with brain gliomas as those reported in the literature using DTI-based tractography.