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The visual scene-network—comprising the parahippocampal place area (PPA), retrosplenial cortex (RSC), and occipital place area (OPA)—shows a prolonged functional development. Structural development of white matter that underlies the scene-network has not been investigated despite its potential influence on scene-network function. The key factor for white matter maturation is myelination. However, research on myelination using the gold standard method of post-mortem histology is scarce. In vivo alternatives diffusion-weighed imaging (DWI) and myelin water imaging (MWI) so far report broad-scale findings that prohibit inferences concerning the scene-network. Here, we combine MWI, DWI tractography, and fMRI to investigate myelination in scene-network tracts in middle childhood, late childhood, and adulthood. We report increasing myelin from middle childhood to adulthood in left RSC-OPA, and trends towards increases in the right RSC-OPA, left PPA-RSC and right PPA-OPA tracts. Moreover, tracts connecting the OPA to the key input region hippocampus showed myelin increases beyond late childhood. Our findings indicate that structural development coincides with functional development in the scene network, possibly enabling structure-function interactions. Highlights Myelin in intrahemispheric scene-network tracts increases beyond late childhood PA-hippocampus tracts also show prolonged myelination Diffusion tensor imaging parameters do not mirror myelin water fraction results

Demyelination is the key pathological process in multiple sclerosis (MS). The extent of demyelination can be quantified with magnetic resonance imaging by assessing the myelin water fraction (MWF). However, long computation times and high noise sensitivity hinder the translation of MWF imaging to clinical practice. In this work, we introduce a more efficient and noise robust method to determine the MWF using a joint sparsity constraint and a pre-computed B1+-T2 dictionary. A single component analysis with this dictionary is used in an initial step to obtain a B1+ map. The T2 distribution is then determined from a reduced dictionary corresponding to the estimated B1+ map using a combination of a non-negativity and a joint sparsity constraint. The non-negativity constraint ensures that a feasible solution with non-negative contribution of each T2 component is obtained. The joint sparsity constraint restricts the T2 distribution to a small set of T2 relaxation times shared between all voxels and reduces the noise sensitivity. The applied Sparsity Promoting Iterative Joint NNLS (SPIJN) algorithm can be implemented efficiently, reducing the computation time by a factor of 50 compared to the commonly used regularized non-negative least squares algorithm. The proposed method was validated in simulations and in 8 healthy subjects with a 3D multi-echo gradient- and spin echo scan at 3 ​T. In simulations, the absolute error in the MWF decreased from 0.031 to 0.013 compared to the regularized NNLS algorithm for SNR ​= ​250. The in vivo results were consistent with values reported in literature and improved MWF-quantification was obtained especially in the frontal white matter. The maximum standard deviation in mean MWF in different regions of interest between subjects was smaller for the proposed method (0.0193) compared to the regularized NNLS algorithm (0.0266). In conclusion, the proposed method for MWF estimation is less computationally expensive and less susceptible to noise compared to state of the art methods. These improvements might be an important step towards clinical translation of MWF measurements.

Chronic liver diseases pose a major health problem worldwide, while common tests for diagnosis and monitoring of diffuse hepatopathy have considerable limitations. Preliminary data on the quantification of hepatic extracellular volume fraction (ECV) with magnetic resonance imaging (MRI) for non-invasive assessment of liver fibrosis are encouraging, with ECV having the potential to overcome several of these constraints.To clinically evaluate ECV provided by quantitative MRI for assessing the severity of liver disease.In this prospective study, multiparametric liver MRI, including T1 mapping and magnetic resonance elastography (MRE), was performed in subjects with and without hepatopathy between November 2018 and October 2019. T1, T2, T2*, proton density fat fraction and stiffness were extracted from parametric maps by regions of interest and ECV was calculated from T1 relaxometries. Serum markers of liver disease were obtained by clinical database research. For correlation analysis, Spearman rank correlation was used. ROC analysis of serum markers and quantitative MRI data for discrimination of liver cirrhosis was performed with MRE as reference standard.109 participants were enrolled (50.7 ± 16.1 years, 61 men). ECV, T1 and MRE correlated significantly with almost all serum markers of liver disease, with ECV showing the strongest associations (up to r = 0.67 with MELD, p 0.01). ECV and T1 correlated with MRE (0.75 and 0.73, p 0.01 each). ECV (AUC 0.89, cutoff 32.2%, sensitivity 85%, specificity 87%) and T1 mapping (AUC 0.85, cutoff 592.5 ms, sensitivity 83%, specificity 75%) featured good performances in detection of liver cirrhosis with only ECV performing significantly superior to model of end stage liver disease (MELD), AST/ALT ratio and international normalized ratio (p 0.01, respectively).Quantification of hepatic extracellular volume fraction with MRI is suitable for estimating the severity of liver disease when using MRE as the standard of reference. It represents a promising tool for non-invasive assessment of liver fibrosis and cirrhosis.

Background and purpose Quantitative T1 and diffusion tensor imaging (DTI) may provide information about pathological changes underlying disability and progression in diseases like multiple sclerosis (MS). Imaging the corpus callosum (CC), a primary site of damage in MS with a critical role in interhemispheric connectivity, may be useful for assessing overall brain health, prognosis, and therapy efficacy. We assessed the feasibility of multisite clinical trials using advanced MRI by examining the intra and intersite reproducibility of T1 and DTI measurements in the CC and segmented white matter (WM). Methods Five healthy volunteers were scanned twice within 24 hours at six 3T sites. Coefficients of variation (COVs) and intraclass correlation coefficients (ICCs) for CC and WM T1 , fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Dax ), and radial diffusivity (Drad ) assessed intrasite and intersite reliability. Results CC and WM T1 showed excellent intrasite reproducibility with low COVs (mean = .90% and .89%, respectively) and good ICCs (CC = .78, WM = .90). T1 also demonstrated intersite reliability (low COVs: CC = 2.4%, WM = 1.8%; moderate ICCs: CC = .43, WM = .69). DTI had low intrasite COVs (CC: FA = 1.3%, MD = 1.5%, Dax = 1.4%, Drad = 2.2%; WM: FA = .9%, MD = .9%, Dax = .7%, Drad = 1.2%) and high intrasite ICCs (CC: FA = .95, MD = .97, Dax = .94, Drad = .97; CC: FA = .9, MD = .66, Dax = .88, Drad = .63), indicating excellent intrasite reproducibility. DTI also showed excellent intersite reliability with low COVs (CC: FA = 2.1%, MD = 4.1%, Dax = 3.4%, Drad = 5.3%, WM: FA = 1.3%, MD = 1.9%, Dax = 1.8%, Drad = 2.1%,) and good ICCs (CC: FA = .90, MD = .84, Dax = .72, Drad = .90; WM: FA = .83, MD = .34, Dax = .62, Drad = .41). Conclusions T1 and DTI measures are reproducible using equivalent MRI scanners and sequence protocols. Using a similar MR system, it is feasible to carry out multicenter studies using T1 and DTI to evaluate changes within the CC and WM.

Demyelination is the key pathological process in multiple sclerosis (MS). The extent of demyelination can be quantified with magnetic resonance imaging by assessing the myelin water fraction (MWF). However, long computation times and high noise sensitivity hinder the translation of MWF imaging to clinical practice. In this work, we introduce a more efficient and noise robust method to determine the MWF using a joint sparsity constraint and a pre-computed B

Limbic encephalitis (LE) is an immune-related disease with limbic symptoms, variable and asymmetric magnetic resonance imaging (MRI) aspects and antibody profiles. This study investigated the diagnostic value of quantitative relaxation times T2 (qT2) and MRI signal intensities (SI) in LE. The prospective 3T-MRI study included 39 epilepsy patients with initially suspected LE and 20 healthy controls. Values and asymmetry indices of qT2, T2-weighted (T2-w) and proton density (PD)-w SI of manually delineated and automatically segmented amygdala and hippocampus were measured. Additionally, two raters made a blinded visual analysis on FLAIR (fluid attenuation inversion recovery) and T2-w images. According to diagnostic guidelines, 22 patients had probable LE and 17 patients had possible LE. The qT2 was higher (p

BACKGROUND AND PURPOSE Late-onset adult Krabbe disease is a very rare demyelinating leukodystrophy, affecting less than 1 in a million people. Hematopoietic stem cell transplantation (HSCT) strategies can stop the accumulation of toxic metabolites that damage myelin-producing cells. We used quantitative advanced imaging metrics to longitudinally assess the impact of HSCT on brain abnormalities in adult-onset Krabbe disease. METHODS A 42-year-old female with late-onset Krabbe disease and an age/sex-matched healthy control underwent annual 3T MRI (baseline was immediately prior to HSCT for the Krabbe subject). Imaging included conventional scans, myelin water imaging, diffusion tensor imaging, and magnetic resonance spectroscopy. RESULTS Brain abnormalities far beyond those visible on conventional imaging were detected, suggesting a global pathological process occurs in Krabbe disease with adult-onset etiology, with myelin being more affected than axons, and evidence of wide-spread gliosis. After HSCT, our patient showed clinical stability in all measures, as well as improvement in gait, dysarthria, and pseudobulbar affect at 7.5 years post-transplant. No MRI evidence of worsening demyelination and axonal loss was observed up to 4 years post-allograft. CONCLUSIONS Clinical evidence and stability of advanced MR measures related to myelin and axons supports HSCT as an effective treatment strategy for stopping progression associated with late-onset Krabbe disease.

Background Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (slMFB) emerges as a - yet experimental - treatment for major depressive disorder (MDD) and other treatment refractory psychiatric diseases. First experiences have been reported from two open label pilot trials in major depression (MDD) and long-term effectiveness for MDD (50 months) has been reported. Objective To give a detailed description of the surgical technique for DBS of the superolateral branch of the medial forebrain bundle (slMFB) in MDD. Methods Surgical experience from bilateral implantation procedures in n = 24 patients with MDD is reported. The detailed procedure of tractography-assisted targeting together with detailed electrophysiology in 144 trajectories in the target region (recording and stimulation) is described. Achieved electrode positions were evaluated based on postoperative helical CT and fused to preoperative high resolution anatomical magnetic resonance imaging (MRI; Philips Medical Systems, Best, Netherlands), including the pre-operative diffusion tensor imaging (DTI) tractographic information (StealthViz DTI, Medtronic, USA; Framelink 5.0, Medtronic, USA). Midcommissural point (MCP) coordinates of effective contact (EC) location, together with angles of entry into the target region were evaluated. To investigate incidental stimulation of surrounding nuclei (subthalamic nucleus, STN; substantia nigra, SNr; and red nucleus, RN) as a possible mechanism, a therapeutic triangle (TT) was defined, located between these structures (based on MRI criteria in T2) and evaluated with respect to EC locations. Results Bilateral slMFB DBS was performed in all patients. We identified an electrophysiological environment (defined by autonomic reaction, passive microelectrode recording, acute effects and oculomotor effects) that helps to identify the proper target site on the operation table. Postoperative MCP-evaluation of effective contacts (EC) shows a significant variability with respect to localization. Evaluation of the TT shows that responders will typically have their active contacts inside the triangle and that surrounding nuclei (STN, SNr, RN) are not directly hit by EC, indicating a predominant white matter stimulation. The individual EC position within the triangle cannot be predicted and is based on individual slMFB (tractography) geometry. There was one intracranial bleeding (FORESEE I study) during a first implantation attempt in a patient who later received full bilateral implantation. Typical oculomotor side effects are idiosyncratic for the target region and at inferior contacts. Conclusion The detailed surgical procedure of slMFB DBS implantation has not been described before. The slMFB emerges as an interesting region for the treatment of major depression (and other psychiatric diseases) with DBS. So far it has only been successfully researched in open label clinical case series and in 15 patients published. Stimulation probably achieves its effect through direct white-matter modulation of slMFB fibers. The surgical implantation comprises a standardized protocol combining tractographic imaging based on DTI, targeting and electrophysiological evaluation of the target region. To this end, slMFB DBS surgery is in technical aspects comparable to typical movement disorder surgery. In our view, slMFB DBS should only be performed under tractographic assistance., Graphical abstract Unlabelled Image, Highlights • The slMFB is an emerging target for DBS in therapy refractory Depression. • The therapeutic effect is related to modulation of white matter. • Surgery for slMFB DBS is tractography assisted surgery. • DBS of the slMFB is in many aspects similar to movement disorder surgery.

PURPOSE: Kinetic parameters derived from dynamic contrast-enhanced MRI (DCE-MRI) were suggested as a possible instrument for multi-parametric lesion characterization, but have not found their way into clinical practice yet due to inconsistent results. The quantification is heavily influenced by the definition of an appropriate arterial input functions (AIF). Regarding brain tumor DCE-MRI, there are currently several co-existing methods to determine the AIF frequently including different brain vessels as sources. This study quantitatively and qualitatively analyzes the impact of AIF source selection on kinetic parameters derived from commonly selected AIF source vessels compared to a population-based AIF model. MATERIAL AND METHODS: 74 patients with brain lesions underwent 3D DCE-MRI. Kinetic parameters [transfer constants of contrast agent efflux and reflux Ktrans and kep and, their ratio, ve, that is used to measure extravascular-extracellular volume fraction and plasma volume fraction vp] were determined using extended Tofts model in 821 ROI from 4 AIF sources [the internal carotid artery (ICA), the closest artery to the lesion, the superior sagittal sinus (SSS), the population-based Parker model]. The effect of AIF source alteration on kinetic parameters was evaluated by tissue type selective intra-class correlation (ICC) and capacity to differentiate gliomas by WHO grade [area under the curve analysis (AUC)]. RESULTS: Arterial AIF more often led to implausible ve >100% values (p0.5 between arterial AIF derived kinetic parameters. Differentiation between WHO III and II glioma was exclusively possible with vp derived from an AIF in the SSS (p=0.03; AUC 0.74). CONCLUSION: The AIF source has a significant impact on absolute kinetic parameters in DCE-MRI, which limits the comparability of kinetic parameters derived from different AIF sources. The effect is also tissue-dependent. The SSS appears to be the best choice for AIF source vessel selection in brain tumor DCE-MRI as it exclusively allowed for WHO grades II/III and III/IV glioma distinction (by vp) and showed the least number of implausible ve values.

Purpose To investigate the effect of the choice of the curve-fitting model on the perfusion fraction (fIVIM) with regard to tissue type characterization, correlation with microvascular anatomy, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters. Several curve-fitting models coexist in intravoxel incoherent motion (IVIM) MRI to derive the (fIVIM). Materials and Methods In all, 29 patients with brain lesions (12 gliomas, 11 meningiomas, three metastases, two gliotic scars, one multiple sclerosis) underwent IVIM-MRI (32 b-values, 0 to 2000 s/mm2) at 3T. fIVIM was determined by classic monoexponential, biexponential, and a novel nonnegative least squares (NNLS) fitting in 352 regions of interest (lesion-containing and normal-appearing tissue) and tested their correlation with DCE-MRI kinetic parameters and microvascular anatomy derived from 57 region of interest (ROI)-based biopsies and their capacities to differentiate histologically different lesions. Results fIVIM differed significantly between all three models and all tissue types (monoexponential confidence interval in percent [CI 3.4–3.8]; biexponential [CI 11.21–12.45]; NNLS [CI 2.06–2.60]; all P < 0.001). For all models an increase in fIVIM was associated with a shift to larger vessels and higher vessel area / tissue area ratio (regression coefficient 0.07–0.52; P = 0.04–0.001). Correlation with kinetic parameters derived from DCE-MRI was usually not significant. Only biexponential fitting allowed differentiation of both gliosis from edema and high- from low-grade glioma (both P < 0.001). Conclusion The curve-fitting model has an important impact on fIVIM and its capacity to differentiate tissues. fIVIM may possibly be used to assess microvascular anatomy and is weakly correlated with DCE-MRI kinetic parameters. Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1187–1199.

Several very rare forms of dementia are associated with characteristic focal atrophy predominantly of the frontal and/or temporal lobes and currently lack imaging solutions to monitor disease. Magnetic resonance fingerprinting (MRF) is a recently developed technique providing quantitative relaxivity maps and images with various tissue contrasts out of a single sequence acquisition. This pilot study explores the utility of MRF-based T1 and T2 mapping to discover focal differences in relaxation times between patients with frontotemporal lobe degenerative dementia and healthy controls. 8 patients and 30 healthy controls underwent a 3 T MRI including an axial 2D spoiled gradient echo MRF sequence. T1 and T2 relaxation maps were generated based on an extended phase graphs algorithm-founded dictionary involving inner product pattern matching. A region of interest (ROI)-based analysis of T1 and T2 relaxation times was performed with FSL and ITK-SNAP. Depending on the brain region analyzed, T1 relaxation times were up to 10.28% longer in patients than in controls reaching significant differences in cortical gray matter (P = .047) and global white matter (P = .023) as well as in both hippocampi (P = .001 left; P = .027 right). T2 relaxation times were similarly longer in the hippocampus by up to 19.18% in patients compared with controls. The clinically most affected patient had the most control-deviant relaxation times. There was a strong correlation of T1 relaxation time in the amygdala with duration of the clinically manifest disease (Spearman Rho = .94; P = .001) and of T1 relaxation times in the left hippocampus with disease severity (Rho = .90, P = .002). In conclusion, MRF-based relaxometry is a promising and time-saving new MRI tool to study focal cerebral alterations and identify patients with frontotemporal lobe degeneration. To validate the results of this pilot study, MRF is worth further exploration as a diagnostic tool in neurodegenerative diseases.

Background and purpose Myelin water imaging (MWI) and diffusion tensor imaging (DTI) provide information about myelin and axon-related brain microstructure, which can be useful for investigating normal brain development and many childhood brain disorders. While pediatric DTI atlases exist, there are no pediatric MWI atlases available for the 9-10 years old age group. As myelination and structural development occurs throughout childhood and adolescence, studies of pediatric brain pathologies must use age-specific MWI and DTI healthy control data. We created atlases of myelin water fraction (MWF) and DTI metrics for healthy children aged 9-10 years for use as normative data in pediatric neuroimaging studies. Methods 3D-T1 , DTI, and MWI scans were acquired from 20 healthy children (mean age: 9.6 years, range: 9.2-10.3 years, 4 females). ANTs and FSL registration were used to create quantitative MWF and DTI atlases. Region of interest (ROI) analysis in nine white matter regions was used to compare pediatric MWF with adult MWF values from a recent study and to investigate the correlation between pediatric MWF and DTI metrics. Results Adults had significantly higher MWF than the pediatric cohort in seven of the nine white matter ROIs, but not in the genu of the corpus callosum or the cingulum. In the pediatric data, MWF correlated significantly with mean diffusivity, but not with axial diffusivity, radial diffusivity, or fractional anisotropy. Conclusions Normative MWF and DTI metrics from a group of 9-10 year old healthy children provide a resource for comparison to pathologies. The age-specific atlases are ready for use in pediatric neuroimaging research and can be accessed: https://sourceforge.net/projects/pediatric-mri-myelin-diffusion/.

The corpus callosum serves the functional integration and interaction between the two hemispheres. Many studies investigate callosal microstructure via diffusion tensor imaging (DTI) fractional anisotropy (FA) in geometrically parcellated segments. However, FA is influenced by several different microstructural properties such as myelination and axon density, hindering a neurobiological interpretation. This study explores the relationship between FA and more specific measures of microstructure within the corpus callosum in a sample of 271 healthy participants. DTI tractography was used to assess 11 callosal segments and gain estimates of FA. We quantified axon density and myelination via neurite orientation dispersion and density imaging (NODDI) to assess intra-neurite volume fraction and a multiecho gradient spin-echo sequence estimating myelin water fraction. The results indicate three common factors in the distribution of FA, myelin content and axon density, indicating potentially shared rules of topographical distribution. Moreover, the relationship between measures varied across the corpus callosum, suggesting that FA should not be interpreted uniformly. More specific magnetic resonance imaging-based quantification techniques, such as NODDI and multiecho myelin water imaging, may thus play a key role in future studies of clinical trials and individual differences.

Axonal myelination is a key white matter maturation process as it increases conduction velocity, synchrony, and reliability. While diffusion tensor imaging (DTI) is sensitive to myelination, it is also sensitive to unrelated microstructural properties, thus hindering straightforward interpretations. Myelin water imaging (MWI) provides a more reliable and direct in vivo measure of myelination. Although early histological studies show protracted myelination from childhood to adulthood, reliable tract-specific in vivo evidence from MWI is still lacking. Here, we combine MWI and DTI tractography to investigate myelination in middle childhood, late childhood, and adulthood in 18 major white matter tracts. In the vast majority of major white matter tracts, myelin water fraction continued to increase beyond late childhood. Our study provides first in vivo evidence for protracted myelination beyond late childhood.

Contrast enhancement of glioblastomas (GBM) is caused by the decrease in relaxation time, T1. Here, we demonstrate that the quantitative measurement of T1 (qT1) discovers a subtle enhancement in GBM patients that is invisible in standard MRI. We assessed the volume change of this “cloudy” enhancement during radio‐chemotherapy and its impact on patients’ progression‐free survival (PFS). We enrolled 18 GBM patients in this observational, prospective cohort study and measured 3T‐MRI pre‐ and post contrast agent with standard T1‐weighted (T1w) and with sequences to quantify T1 before radiation, and at 6‐week intervals during radio‐chemotherapy. We measured contrast enhancement by subtracting pre from post contrast contrast images, yielding relative signal increase ∆T1w and relative T1 shortening ∆qT1. On ∆qT1, we identified a solid and a cloudy‐enhancing compartment and evaluated the impact of their therapy‐related volume change upon PFS. In ∆qT1 maps cloudy‐enhancing compartments were found in all but two patients at baseline and in all patients during therapy. The qT1 decrease in the cloudy‐enhancing compartment post contrast was 21.64% versus 1.96% in the contralateral control tissue (P

Purpose To determine whether differences in hydration state, which could arise from routine clinical procedures such as overnight fasting, affect brain total water content (TWC) and brain volume measured with magnetic resonance imaging (MRI). Materials and Methods Twenty healthy volunteers were scanned with a 3T MR scanner four times: day 1, baseline scan; day 2, hydrated scan after consuming 3L of water over 12 hours; day 3, dehydrated scan after overnight fasting of 9 hours, followed by another scan 1 hour later for reproducibility. The following MRI data were collected: T2 relaxation (for TWC measurement), inversion recovery (for T1 measurement), and 3D T1-weighted (for brain volumes). Body weight and urine specific gravity were also measured. TWC was calculated by fitting the T2 relaxation data with a nonnegative least-squares algorithm, with corrections for T1 relaxation and image signal inhomogeneity and normalization to ventricular cerebrospinal fluid. Brain volume changes were measured using SIENA. TWC means were calculated within 14 tissue regions. Results Despite indications of dehydration as demonstrated by increases in urine specific gravity (P = 0.03) and decreases in body weight (P = 0.001) between hydrated and dehydrated scans, there was no measurable change in TWC (within any brain region) or brain volume between hydration states. Conclusion We demonstrate that within a range of physiologic conditions commonly encountered in routine clinical scans (no pretreatment with hydration, well hydrated before MRI, and overnight fasting), brain TWC and brain volumes are not substantially affected in a healthy control cohort. J. Magn. Reson. Imaging 2016;44:296–304.

Myelination of axons in the central nervous system is critical for human cognition and behavior. The predominant protein in myelin is proteolipid protein—making PLP1, the gene that encodes for proteolipid protein, one of the primary candidate genes for white matter structure in the human brain. Here, we investigated the relation of genetic variation within PLP1 and white matter microstructure as assessed with myelin water fraction imaging, a neuroimaging technique that has the advantage over conventional diffusion tensor imaging in that it allows for a more direct assessment of myelin content. We observed significant asymmetries in myelin water fraction that were strongest and rightward in the parietal lobe. Importantly, these parietal myelin water fraction asymmetries were associated with genetic variation in PLP1. These findings support the assumption that genetic variation in PLP1 affects white matter myelination in the healthy human brain.

Quantitative TFive healthy volunteers were scanned twice within 24 hours at six 3T sites. Coefficients of variation (COVs) and intraclass correlation coefficients (ICCs) for CC and WM TCC and WM TT

Purpose:To assess the extent of demyelination in cervical spondylotic myelopathy (CSM) using myelin water imaging (MWI) and electrophysiologic techniques.Methods:Somatosensory evoked potentials (SSEPs) and MWI were acquired in 14 patients with CSM and 18 age-matched healthy controls. MWI was performed on a 3.0T whole body magnetic resonance scanner. Myelin water fraction (MWF) was extracted for the dorsal columns and whole cord. SSEPs and MWF were also compared with conventional MRI outcomes, including T2 signal intensity, compression ratio, maximum spinal cord compression (MSCC), and maximum canal compromise (MCC).Results:Group analysis showed marked differences in T2 signal intensity, compression ratio, MSCC, and MCC between healthy controls and patients with CSM. There were no group differences in MWF and SSEP latencies. However, patients with CSM with pathologic SSEPs exhibited reduction in MWF (p < 0.05). MWF was also correlated with SSEP latencies.Conclusion:Our findings provide evidence of decreased myelin content in the spinal cord associated with impaired spinal cord conduction in patients with CSM. While conventional MRI are of great value to define the extent of cord compression, they show a limited correlation with functional deficits (i.e., delayed SSEPs). MWI provides independent and complementary readouts to spinal cord compression, with a high specificity to detect impaired conduction.

BACKGROUND AND PURPOSE: Experienced freedivers can endure prolonged breath-holds despite severe hypoxemia and are therefore ideal subjects to study apnea-induced cerebrovascular reactivity. This multiparametric study investigated CBF, the spatial coefficient of variation as a correlate of arterial transit time and brain metabolism, dynamics during prolonged apnea.MATERIALS AND METHODS: Fifteen male freedivers (age range, 20-64 years; cumulative previous prolonged breath-holds >2 minutes and 30 seconds: 4-79,200) underwent repetitive 3T pseudocontinuous arterial spin-labeling and 31P-/1H-MR spectroscopy before, during, and after a 5-minute breath-hold (split into early and late phases) and gave temporally matching venous blood gas samples. Correlation of temporal and regional cerebrovascular reactivity to blood gases and cumulative previous breath-holds of >2 minutes and 30 seconds in a lifetime was assessed.RESULTS: The spatial coefficient of variation of CBF (by arterial spin-labeling) decreased during the early breath-hold phase (-30.0%, P = .002), whereas CBF remained almost stable during this phase and increased in the late phase (+51.8%, P = .001). CBF differed between the anterior and the posterior circulation during all phases (eg, during late breath-hold: MCA, 57.3 ± 14.2 versus posterior cerebral artery, 42.7 ± 10.8 mL/100 g/min; P = .001). There was an association between breath-hold experience and lower CBF (1000 previous breath-holds reduced WM CBF by 0.6 mL/100 g/min; 95% CI, 0.15-1.1 mL/100 g/min; P = .01). While breath-hold caused peripheral lactate rise (+18.5%) and hypoxemia (oxygen saturation, -24.0%), cerebral lactate and adenosine diphosphate remained within physiologic ranges despite early signs of oxidative stress [-6.4% phosphocreatine / (adenosine triphosphate + adenosine diphosphate); P = .02].CONCLUSIONS: This study revealed that the cerebral energy metabolism of trained freedivers withstands severe hypoxic hypercarbia in prolonged breath-hold due to a complex cerebrovascular hemodynamic response.

Measurement of basic quantitative magnetic resonance (MR) parameters (e.g., relaxation times T1, T2*, T2 or respective rates R (1/T)) corrected for radiofrequency (RF) coil bias yields different conventional and new tissue contrasts as well as volumes for tissue segmentation. This approach also provides quantitative measures of microstructural and functional tissue changes. We herein demonstrate some prospects of quantitative MR imaging in neurological diagnostics and science.

Deep brain stimulation alleviates tremor of various origins. Several regions like the ventralis intermediate nucleus of thalamus, the caudal zona incerta, and the posterior subthalamic region are generally targeted. Previous work with fiber tractography has shown the involvement of the cerebello-thalamo-cortical network in tremor control.To report the results of a prospective trial in a group of patients with tremor who underwent post hoc tractographic analysis after treatment with traditional thalamic deep brain stimulation.A total of 11 patients (aged 64 ± 17 years, 6 male) were enrolled (essential tremor [6], Parkinson tremor [3], and myoclonic tremor in myoclonus dystonia [2]). Patients received 1 (3 patients), 2 (7 patients), or 3 (1 patient) quadripolar electrodes. A 32-direction diffusion tensor magnetic resonance imaging sequence was acquired preoperatively. Tractography was processed postoperatively for evaluation and the dentato-rubro-thalamic tract (DRT) was individually tracked. Electrode positions were determined with helical computed tomography. Electric fields (EFs) were simulated according to individual stimulation parameters in a standardized atlas brain space (ICBM-MNI 152).Tremor was reduced in all patients (69.4% mean) on the global (bilateral) tremor score. Effective contacts were located inside or in proximity to the DRT. In moderate tremor reduction (2 patients), the EFs were centered on its anterior border. In good and excellent tremor reduction (9 patients), EFs focused on its center.Deep brain stimulation of the cerebello-thalamo-cortical network reduces tremor. The DRT connects 3 traditional target regions for deep brain stimulation in tremor disease. Tractography techniques can be used to directly visualize the DRT and, therefore, optimize target definition in individual patients.

To assess if ratios of T1-weighted (T1w) signal intensity (SI) and quantitative T1 relaxometry (qT1) change on serial administration of macrocyclic gadobutrol. A total of 17 glioblastoma patients were scanned at 3.0 T magnetic resonance imaging (MRI) every 6 weeks after tumor resection with standard MRI and T1 and T2 relaxometry before and after gadobutrol administration. On co-registered images T1w SI was measured and relaxation times T1 (qT1) and quantitative T2 (qT2) were quantified in several deep grey matter nuclei as ratios relative to frontal white matter and to the pons. Ratio changes were evaluated over time with a paired t‑test and multiple regression. An average of 8 (range 5–14) scans per patient were completed. Ratios of T1w SI, qT1 and qT2 remained unchanged for all target regions from the first to the last time point (p > 0.05) and did not correlate with the number of gadobutrol administrations. Multivariate regression showed no significant impact of gadobutrol on qT1 or qT2 ratios, but a significant negative effect on T1w SI ratios. Gender also had no impact on the ratios but age had a significant negative influence on the qT1 ratio. Multiple administrations of a macrocyclic contrast agent did not change relaxation time T1 ratios in any deep grey matter structure.

// Elke Hattingen 1, * , Andreas Muller 1, * , Alina Jurcoane 1 , Burkhard Madler 2 , Philip Ditter 1 , Hans Schild 1 , Ulrich Herrlinger 3 , Martin Glas 3, 4, 5, 6, * and Sied Kebir 3, 4, 6, * 1 Neuroradiology, Department of Radiology, University Hospital Bonn, Bonn, Germany 2 Philips GmbH, UB Healthcare, Hamburg, Germany 3 Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Bonn, Germany 4 Stem Cell Pathologies Group, Institute of Reconstructive Neurobiology, Bonn, Germany 5 Clinical Cooperation Unit Neurooncology, MediClin Robert Janker Klinik, Bonn, Germany 6 Division of Clinical Neurooncology, Department of Neurology, University of Essen Medical Center, Essen, Germany * These authors have contributed equally to this work Correspondence to: Elke Hattingen, email: elke.hattingen@ukb.uni-bonn.de Keywords: T1-mapping, quantitative MRI, BBB damage, glioblastoma, T1-relaxometry Received: February 14, 2017 Accepted: May 22, 2017 Published: June 27, 2017 SUMMARIZING THE IMPORTANCE OF THE STUDY The repetitive usage of gadolinium-based contrast agents (GBCA) is critical for magnetic resonance imaging (MRI) evaluation of tumor burden in glioblastoma patients. It is also a crucial tool for determination of radiographical response to treatment. GBCA injection, however, comes with a 2.4% rate of adverse events including life-threatening conditions such as nephrogenic systemic fibrosis (NSF). Moreover, GBCA have been shown to be deposited in brain tissue of patients even with an intact blood-brain barrier (BBB). The present study explores quantitative T1 relaxometry as an alternative non-invasive imaging technique detection of tumor burden and determination of radiographical response. This technique exploits specific properties of brain tissue with impaired BBB. With a sensitivity and specificity as high as 86% and 80%, respectively, quantitative T1-relaxometry allows for detecting contrast-enhancing areas without the use of GBCA. This method could make it unnecessary to subject patients to the risk of adverse events associated with the use of GBCA. Nonetheless, a large-scale analysis is needed to confirm our findings. ABSTRACT Background: Gadolinium-based contrast agents (GBCA) are crucial for magnetic resonance imaging (MRI)-based evaluation of tumor burden in glioblastoma (GBM). Serious adverse events of GBCA, even though uncommon, and gadolinium deposition in brain tissue could be avoided by novel imaging techniques not requiring GBCA. Altered tissue composition in areas with impaired blood-brain-barrier also alters the quantified T1 relaxation time (qT1), so that qT1 analysis could replace GBCA-based MRI for the analysis of tumor burden and response. Methods: As a part of a prospective pilot MRI-relaxometry trial, patients with newly-diagnosed GBM who relapsed under standard radiochemotherapy were selected for this study. At recurrence, subtraction of qT1 maps pre and post-GBCA application (ΔqT1 maps) was used to determine areas of contrast-enhancement. With the contrast-enhancement on ΔqT1 maps as reference, ROC analysis served to detect an optimal qT1 cut-off on qT1 maps prior to GBCA to distinguish between contrast-enhancing tissue and its surroundings. Results: Ten patients were included. A qT1 value >2051ms predicted contrast-enhancing tumor tissue with a sensitivity of 86% and specificity of 80% (AUC, 0.92; p 2051 ms that did not overlap with contrast-enhancing area transformed into contrast-enhancement later on (n=4). Conclusion: T1-relaxometry may be a useful technique to assess tissue properties equivalent to contrast-enhancement without the need for GBCA application. It may also provide information on sites with future tumor progression. Nonetheless, large-scale studies are needed to confirm these findings.

Hintergrund Die tiefe Hirnstimulation („deep brain stimulation“, DBS) zur Behandlung der Epilepsie im Nucleus anterior thalami (ANT) ist seit 2010 in Europa zugelassen. Obschon sie fur alle fokalen Epilepsien zugelassen ist, stellt sich die Frage, ob bestimmte kortikale Epilepsieursprungsorte (z. B. frontal und temporal) besser als andere fur diese Therapie empfanglich sind.

Purpose To assess the reproducibility of myelin water fraction (MWF) and geometric mean T2 (GMT2), which are in vivo markers of pathological changes underlying disability and progression in diseases such as multiple sclerosis. Materials and Methods Five healthy volunteers were scanned twice within 24 hours at six different sites using the same manufacturer's 3T magnetic resonance (MR) system. T2 distributions were produced by fitting multiecho 3D T2 data using non-negative least squares, with stimulated echo correction. MWF, the fraction of signal with T2 between 15 and 40 msec to the entire signal, and GMT2, the mean T2 on a logarithmic scale from T2 between 40 and 200 msec, were examined in white matter. Results Intrasite coefficients of variation (COVs) were low (mean 3.99% for MWF and 0.51% for GMT2), as were intersite COVs (mean 4.68% for MWF, 0.31% for GMT2). Scan–rescan intraclass correlation coefficients (ICCs) (0.76 for MWF and 0.93 for GMT2) and Bland–Altman plots indicated good agreement between single site scans. Intersite ICCs were relatively high (0.69 for MWF and 0.92 for GMT2), revealing good intersite reliability. Conclusion MWF and GMT2 measures are reproducible between scans and across sites with an equivalent MR scanner and sequence protocol. Multicenter clinical trials using quantitative T2 relaxation are feasible. J. Magn. Reson. Imaging 2013;38:1445–1453. © 2013 Wiley Periodicals, Inc.

To investigate the effect of the choice of the curve-fitting model on the perfusion fraction (fIn all, 29 patients with brain lesions (12 gliomas, 11 meningiomas, three metastases, two gliotic scars, one multiple sclerosis) underwent IVIM-MRI (32 b-values, 0 to 2000 s/mmfThe curve-fitting model has an important impact on f2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1187-1199.

The current study examined auditory processing deficits in dyslexia using a dichotic pitch stimulus and functional MRI. Cortical activation by the dichotic pitch task occurred in bilateral Heschl’s gyri, right planum temporale, and right superior temporal sulcus. Adolescents with dyslexia, relative to age-matched controls, illustrated greater activity in left Heschl’s gyrus for random noise, less activity in right Heschl’s gyrus for all auditory conditions, and less activity in right superior temporal sulcus for a dichotic melody. Subsequent analyses showed that these group differences were attributable to dyslexic readers who performed poorly on the psychophysical task. Furthermore, behavioral performance on phonological reading was correlated to activity from dichotic conditions in right Heschl’s gyrus and right superior temporal sulcus. It is postulated that these differences between reader groups is primarily due to a noise exclusion deficit shown previously in dyslexia.

Myelin water imaging, a magnetic resonance imaging technique capable of resolving the fraction of water molecules which are located between the layers of myelin, is a valuable tool for investigating both normal and pathological brain structure in vivo. There is a strong need for pulse sequences which improve the quality and applicability of myelin water imaging in a clinical setting. In this study, we validated the use of a fast multi echo T(2) relaxation sequence for myelin water imaging. Using a multiple combined gradient and spin echo (GRASE) technique, we attain whole cerebrum myelin water images in under 15 minutes. Region of interest analysis indicates that this fast GRASE imaging sequence produces results which are in good agreement with pure spin echo measurements (R(2)=0.95, p0.0001). This drastic improvement in speed and brain coverage compared to current spin echo standards will allow increased inclusion of myelin water imaging in neurological research protocols and opens up the possibility of applications in a clinical setting.

The medial forebrain bundle (MFB), a key structure of reward-seeking circuitry, remains inadequately characterized in humans despite its vast importance for emotional processing and development of addictions and depression. Using Diffusion Tensor Imaging Fiber Tracking (DTI FT) the authors describe potential converging ascending and descending MFB and anterior thalamic radiation (ATR) that may mediate major brain reward-seeking and punishment functions. Authors highlight novel connectivity, such as supero-lateral-branch MFB and ATR convergence, caudally as well as rostrally, in the anterior limb of the internal capsule and medial prefrontal cortex. These anatomical convergences may sustain a dynamic equilibrium between positive and negative affective states in human mood-regulation and its various disorders, especially evident in addictions and depression.

We propose a multicomponent fitting algorithm for multiecho T(2) data which allows for correction of T(2) distributions in the presence of stimulated echoes. Tracking the population of spins in many coherence pathways via the iterated method of the Extended Phase Graph algorithm allows for accurate quantification of echo magnitudes. The resulting decay curves allow for correction of errors due to nonideal refocusing pulses as a result of inhomogeneities in the B(1) transmit field. Non-Negative Least Squares fitting is used to quantify the magnitude of T(2) components at various T(2) values. This method, allowing calculation of the T(2) distribution with simultaneous extraction of the refocusing pulse flip angle, requires no change to image acquisition procedures and no extra data input. Validation by means of both simulations and in vivo data shows excellent interscan reproducibility while vastly improving the accuracy of extracted T(2) parameters in voxels where poor B(1) homogeneity leads to refocusing pulse flip angles significantly less than 180°. Most notably, myelin water fraction values in these regions are found to have increased consistency and accuracy.

Diffusion Tensor Imaging (DTI) allows the non-invasive study of muscle fiber architecture but musculoskeletal DTI suffers from low signal-to-noise ratio. Noise in the computed tensor fields can lead to poorly reconstructed muscle fiber fields. This paper describes an algorithm for producing denoised muscle fiber fields from noisy diffusion tensor data as well as its preliminary validation. The algorithm computes a denoised vector field by finding the components of its Helmholtz-Hodge decomposition that optimally match the diffusion tensor field. A key feature of the algorithm is that it performs denoising of the vector field simultaneously with its extraction from the noisy tensor field. This allows the vector field reconstruction to be constrained by the architectural properties of skeletal muscles. When compared to primary eigenvector fields extracted from noisy synthetic data, the denoised vector fields show greater similarity to the ground truth for signal-to-noise ratios ranging from 20 to 5. Similarity greater than 0.9 (in terms of fiber direction) is observed for all signal-to-noise ratios, for smoothing parameter values greater than or equal to 10 (larger values yield more smoothing). Fiber architectures were computed from human forearm diffusion tensor data using extracted primary eigenvectors and the denoised data. Qualitative comparison of the fiber fields showed that the denoised fields were anatomically more plausible than the noisy fields. From the results of experiments using both synthetic and real MR datasets we conclude that the denoising algorithm produces anatomically plausible fiber architectures from diffusion tensor images with a wide range of signal-to-noise ratios.

Background Deep brain stimulation (DBS) has been proven to alleviate tremor of various origins. Distinct regions have been targeted. One explanation for good clinical tremor control might be the involvement of the dentatorubrothalamic tract (DRT) as has been suggested in superficial (thalamic) and inferior (posterior subthalamic) target regions. Beyond a correlation with atlas data and the postmortem evaluation of patients treated with lesion surgery, proof for the involvement of DRT in tremor reduction in the living, the scope of this work, is elusive. Objective To report a case of unilateral refractory tremor in tremor-dominant Parkinson disease treated with thalamic DBS. Methods Preoperative diffusion tensor imaging (DTI) was performed. Correlation with individual DBS electrode contact locations was obtained through postoperative fusion of helical computed tomography (CT) data with DTI fiber tracking. Results Tremor was alleviated effectively. An evaluation of the active electrode contact position revealed clear involvement of the DRT in tremor control. A closer evaluation of clinical effects and side effects revealed a highly detailed individual fiber map of the subthalamic region with DTI fiber tracking. Conclusion This is the first time the involvement of the DRT in tremor reduction through DBS has been shown in the living. The combination of DTI with postoperative CT and the evaluation of the electrophysiological environment of distinct electrode contacts led to an individual detailed fiber map and might be extrapolated to refined DTI-based targeting strategies in the future. Data acquisition for a larger study group is the topic of our ongoing research.

The purpose of this work was to compare diagnostic accuracy of Diffusion Tensor Imaging (DTI), Dynamic Contrast Enhanced MRI (DCE MRI), and their combination in diagnosing prostate cancer. Twenty five patients with clinical suspicion of prostate cancer underwent MRI, prior to transrectal ultrasound (TRUS)-guided biopsies. MRI data were correlated to biopsy results. Logistic regression models were constructed for the DTI parameters, DCE MRI parameters, and their combination. The areas under the Receiver Operator Characteristic curves (AUC) were compared between the models. The nonparametric Wilcoxon signed rank test was used for statistical analysis. The sensitivity and specificity values were respectively 81% (74% – 87%) and 85% (79% – 90%) for DTI and 63% (55% – 70%) and 90% (85% – 94%) for DCE. The combination “DTI or DCE MRI” had 100% (97% – 100%) sensitivity and 77% (69% – 83%) specificity, while “DTI and DCE MRI” had 44% (37% – 52%) sensitivity and 98% (94% – 100%) specificity. The AUC for DTI + DCE parameters was significantly higher than that for either DTI (0.96 vs. 0.92, p = 0.0143) or DCE MRI parameters (0.96 vs. 0.87, p = 0.00187) alone. In conclusion, the combination of DTI and DCE MRI has significantly better accuracy in prostate cancer diagnosis than either technique alone.

Multicomponent T(2) relaxation imaging can be used to measure signal from water trapped between myelin bilayers; the ratio of myelin water signal to total water is termed the myelin water fraction (MWF). The goal of this study was to implement and develop the single-slice T(2)-imaging technique proposed by Poon and Henkelman. For refinement, scan parameters (gradient crusher height and slew rate, bandwidth, echo spacing, matrix size, repetition time, and phase rewinding) were varied in water-based phantoms and in fixed and in vivo brain. Changes in the standard deviation of the residuals of the multiexponential fit, MWF, T(2), and peak width of the intra/extracellular water were monitored to determine which scan parameters minimized artifacts. Subsequently, we compared multicomponent T(2) measurements at 1.5T and 3.0T for 10 healthy volunteers, and investigated the differences in SNR, fit residuals, MWF, and T(2) and peak width of the intra/extracellular water, at higher magnetic field. MWF maps were found to be qualitatively similar between field strengths. MWFs were found to be significantly higher at 3.0T than at 1.5T, but with a strongly significant correlation between measurements (R(2) > 0.92, P < 0.0005). The signal-to-noise ratio (SNR) was nearly double at 3.0T, but the standard deviation of residuals was increased in most cases.

We compare T2-relaxation and diffusion tensor data from normal human brain. The relationships between myelin-water fraction (MWF) and various diffusion tensor measures [e.g., fractional anisotropy (FA), perpendicular diffusivity (ADC⊥) and mean diffusivity ] in white matter (WM) and gray matter (GM) structures in the brain were examined in 16 normal volunteers at 1.5 T and 6 normal subjects at 3.0 T and mean diffusivity. We found some degree of linear correlation between these measurements, but by using region of interest (ROI)-based analysis, we also observed several structures which seemed to deviate significantly from a linear relationship. From all investigated relationships between various diffusion tensor measures and myelin-water content, FA and ADC⊥ yielded the highest correlation coefficients with MWF. However, diffusion anisotropy was also significantly influenced by factors other than myelin-water content. The less operator-dependent voxel-based analysis (VBA) between myelin-water and diffusional anisotropy measures is proposed as an innovative alternative to ROI-based analysis. We confirmed that WM structures, in general, have higher diffusional anisotropy than GM structures and also have higher myelin-water content. However, our findings suggest that in the highly organized fibre arrangement of compact WM structures such as the genu of the corpus callosum, elevated degrees of diffusional anisotropies are measured, which do not necessarily correspond to an elevated myelin content but more likely reflect the highly organized directionality of fibre bundles in these areas (low microscopic and macroscopic tortuosity) as well as strongly restricted diffusion in the interstitial space between the myelinated axons. Conversely, in structures with disorganized fibre bundles and multiple fibre crossings, such as the minor and major forceps, low FA values were measured, which does not necessarily reflect a decrease myelin-water content.

To prospectively assess relative water content (RWC), myelin water fraction (MWF), and hydrogen 1 magnetic resonance (MR) spectroscopy findings in the white matter (WM) of patients with phenylketonuria (PKU).This study was approved by the institution's investigational review board, and informed consent was obtained. T2 water relaxation data were acquired by using a 48-echo measurement in a transverse plane through the genu and splenium of the corpus callosum in 16 patients (six men, 10 women; age range, 18-40 years) with PKU and 16 age- and sex-matched control subjects. MR spectroscopy was performed in a voxel (94x70x15 mm) above the ventricles. WM in control subjects (defined as normal WM) was compared with normal-appearing WM (NAWM) and diffuse WM lesions in patients with PKU by using a Student t test.Patients with PKU had two forms of NAWM: (a) areas that looked normal on intermediate-weighted (IW) and T2-weighted MR images and long T2 maps and (b) areas that looked normal on IW and T2-weighted MR images but were hyperintense on long T2 maps. Both forms of NAWM showed increased RWC (up to 2.5%, P.001) and reduced MWF (up to 56%, P.001) relative to normal WM; these changes paralleled those seen in diffuse WM lesions. Approximately 9% of the water in diffuse WM lesions was in a reservoir with a long T2 time of 200-800 msec. Myoinositol concentrations were reduced by 14% (P=.003) in patients with PKU.In patients with PKU, NAWM and diffuse WM lesions have altered RWC and MWF relative to normal WM, and diffuse WM lesions show a redistribution of water into an extracellular reservoir with a long T2 time.

To determine whether differences in hydration state, which could arise from routine clinical procedures such as overnight fasting, affect brain total water content (TWC) and brain volume measured with magnetic resonance imaging (MRI).Twenty healthy volunteers were scanned with a 3T MR scanner four times: day 1, baseline scan; day 2, hydrated scan after consuming 3L of water over 12 hours; day 3, dehydrated scan after overnight fasting of 9 hours, followed by another scan 1 hour later for reproducibility. The following MRI data were collected: T2 relaxation (for TWC measurement), inversion recovery (for T1 measurement), and 3D T1 -weighted (for brain volumes). Body weight and urine specific gravity were also measured. TWC was calculated by fitting the T2 relaxation data with a nonnegative least-squares algorithm, with corrections for T1 relaxation and image signal inhomogeneity and normalization to ventricular cerebrospinal fluid. Brain volume changes were measured using SIENA. TWC means were calculated within 14 tissue regions.Despite indications of dehydration as demonstrated by increases in urine specific gravity (P = 0.03) and decreases in body weight (P = 0.001) between hydrated and dehydrated scans, there was no measurable change in TWC (within any brain region) or brain volume between hydration states.We demonstrate that within a range of physiologic conditions commonly encountered in routine clinical scans (no pretreatment with hydration, well hydrated before MRI, and overnight fasting), brain TWC and brain volumes are not substantially affected in a healthy control cohort. J. Magn. Reson. Imaging 2016;44:296-304.

BACKGROUND AND PURPOSE: Diffusion tensor imaging fiber tractography–assisted planning of deep brain stimulation is an emerging technology. We investigated its accuracy by using electrophysiology under clinical conditions. We hypothesized that a level of concordance between electrophysiology and DTI fiber tractography can be reached, comparable with published modeling approaches for deep brain stimulation surgery. MATERIALS AND METHODS: Eleven patients underwent subthalamic nucleus deep brain stimulation. DTI scans and high-resolution T1- and T2-weighted MR imaging was performed at 3T. Corticospinal tracts were traced. We studied electrode positions and current amplitudes that elicited corticospinal tract effects during the operation to determine relative corticospinal tract distance. Postoperatively, 3D deep brain stimulation electrode contact locations and stimulation patterns were applied for the same corticospinal tract distance estimation. RESULTS: Intraoperative electrophysiologic ( n = 40) clinical effects in 11 patients were detected. The mean intraoperative electrophysiologic corticospinal tract distance was 3.0 ± 0.6 mm; the mean image-derived corticospinal tract distance (DTI fiber tractography) was 3.0 ± 1.3 mm. The 95% limits of agreement were ±2.4 mm. Postoperative electrophysiology ( n = 44) corticospinal tract activation effects were encountered in 9 patients; 39 were further evaluated. Mean electrophysiologic corticospinal tract distance was 3.7 ± 0.7 mm; for DTI fiber tractography, it was 3.2 ± 1.9 mm. The 95% limits of agreement were ±2.5 mm. CONCLUSIONS: DTI fiber tractography depicted the medial corticospinal tract border with proved concordance. Although the overall range of measurements was relatively small and variance was high, we believe that further use of DTI fiber tractography to assist deep brain stimulation procedures is advisable if inherent limitations are respected. These results confirm our previously published electric field simulation studies.

Recently, stimulation-induced hypogeusia in thalamic deep brain stimulation (DBS) for essential tremor has been described in two case reports,1 ,2 suggesting an exceptional occurrence. Surprisingly, an inquiry among 16 patients with thalamic DBS revealed that half of them suffered from stimulation-induced hypogeusia. We hypothesise that the distance between the volume of activated tissue (VAT) and the assumed course of gustatory fibres determines the manifestation of this side effect. We expect to observe shorter distances or even an overlap in patients with stimulation-induced hypogeusia, and a correlation between these distances and the gustometry performance. Informed consent was obtained from the 16 patients, who suffered from essential tremor (11), tremor-dominant Parkinson’s disease (3) or dystonic head tremor (2), respectively. Two patients with a tremor-dominant Parkinson’s disease had received a unilateral DBS-system. None of the patients reported taste disturbances prior to DBS implantation. Six patients refused to take part in the gustometry. The medial lemniscus (ML) and dentato-rubro-thalamic tract (DRT) were determined tractographically in relation to effective electrode contact positions, and the surrounding electric field was visualised as VAT (figure 1A–C). For details regarding imaging, tractography and calculation of electric fields, please refer to our previous publication.3 The gustatory pathway is not traceable tractographically due to its small volume and curved course. However, the human gustatory tract between the nucleus of the solitary tract and the thalamic ventral posteromedial nucleus has been defined by lesion cases, suggesting a course adjacent to the medial margin of the ML at their entrance into the thalamus.4 Thus we used the position of the medial margin of the ML as a substitute measurement for the position of the gustatory tract in this …